Unfolding Role of a Danger Molecule Adenosine Signaling in Modulation of Microbial Infection and Host Cell Response

Directory of Open Access Journals (Sweden)

Jaden S. Lee

2018-01-01

Full Text Available Ectonucleotidases CD39 and CD73, specific nucleotide metabolizing enzymes located on the surface of the host, can convert a pro-inflammatory environment driven by a danger molecule extracellular-ATP to an adenosine-mediated anti-inflammatory milieu. Accordingly, CD39/CD73 signaling has been strongly implicated in modulating the intensity, duration, and composition of purinergic danger signals delivered to host. Recent studies have eluted potential roles for CD39 and CD73 in selective triggering of a variety of host immune cells and molecules in the presence of pathogenic microorganisms or microbial virulence molecules. Growing evidence also suggests that CD39 and CD73 present complimentary, but likely differential, actions against pathogens to shape the course and severity of microbial infection as well as the associated immune response. Similarly, adenosine receptors A2A and A2B have been proposed to be major immunomodulators of adenosine signaling during chronic inflammatory conditions induced by opportunistic pathogens, such as oral colonizer Porphyromonas gingivalis. Therefore, we here review the recent studies that demonstrate how complex network of molecules in the extracellular adenosine signaling machinery and their interactions can reshape immune responses and may also be targeted by opportunistic pathogens to establish successful colonization in human mucosal tissues and modulate the host immune response.

Perception of social cues of danger in autism spectrum disorders.

Directory of Open Access Journals (Sweden)

Nicole R Zürcher

Full Text Available Intuitive grasping of the meaning of subtle social cues is particularly affected in autism spectrum disorders (ASD. Despite their relevance in social communication, the effect of averted gaze in fearful faces in conveying a signal of environmental threat has not been investigated using real face stimuli in adults with ASD. Here, using functional MRI, we show that briefly presented fearful faces with averted gaze, previously shown to be a strong communicative signal of environmental danger, produce different patterns of brain activation than fearful faces with direct gaze in a group of 26 normally intelligent adults with ASD compared with 26 matched controls. While implicit cue of threat produces brain activation in attention, emotion processing and mental state attribution networks in controls, this effect is absent in individuals with ASD. Instead, individuals with ASD show activation in the subcortical face-processing system in response to direct eye contact. An effect of differences in looking behavior was excluded in a separate eye tracking experiment. Our data suggest that individuals with ASD are more sensitive to direct eye contact than to social signals of danger conveyed by averted fearful gaze.

Heme as a danger molecule in pathogen recognition.

Science.gov (United States)

Wegiel, Barbara; Hauser, Carl J; Otterbein, Leo E

2015-12-01

Appropriate control of redox mechanisms are critical for and effective innate immune response, which employs multiple cell types, receptors and molecules that recognize danger signals when they reach the host. Recognition of pathogen-associated pattern molecules (PAMPs) is a fundamental host survival mechanism for efficient elimination of invading pathogens and resolution of the infection and inflammation. In addition to PAMPs, eukaryotic cells contain a plethora of intracellular molecules that are normally secured within the confines of the plasma membrane, but if liberated and encountered in the extracellular milieu can provoke rapid cell activation. These are known as Alarmins or Danger-Associated Molecular Patterns (DAMPs) and can be released actively by cells or passively as a result of sterile cellular injury after trauma, ischemia, or toxin-induced cell rupture. Both PAMPs and DAMPs are recognized by a series of cognate receptors that increase the generation of free radicals and activate specific signaling pathways that result in regulation of a variety of stress response, redox sensitive genes. Multiple mediators released, as cells die include, but are not limited to ATP, hydrogen peroxide, heme, formyl peptides, DNA or mitochondria provide the second signal to amplify immune responses. In this review, we will focus on how sterile and infective stimuli activate the stress response gene heme oxygenase-1 (Hmox1, HO-1), a master gene critical to an appropriate host response that is now recognized as one with enormous therapeutic potential. HO-1 gene expression is regulated in large part by redox-sensitive proteins including but not limited to nrf2. Both PAMPs and DAMPs increase the activation of nrf2 and HO-1. Heme is a powerful pro-oxidant and as such should be qualified as a DAMP. With its degradation by HO-1a molecule of carbon monoxide (CO) is generated that in turn serves as a bioactive signaling molecule. PAMPs such as bacterial endotoxin activate HO-1

Le « signalement d’enfant en danger ». Une problématique de l’événement

OpenAIRE

Collinot, André

2011-01-01

L’analyse proposée met en relation la pratique de signalement d’enfant en danger d’une institution, l’Aide Sociale à l’Enfance, et le terme d’événement pris dans son usage épistémique en analyse du discours. Aux étapes du signalement correspondent diverses instances « mettant en récit » des événements mondains, selon deux processus discursifs distincts, établissant ainsi interaction entre une appréhension d’un événement qui a eu lieu et sa compréhension en tant qu’événement discursif. La noti...

Extravascular red blood cells and hemoglobin promote tumor growth and therapeutic resistance as endogenous danger signals.

Science.gov (United States)

Yin, Tao; He, Sisi; Liu, Xiaoling; Jiang, Wei; Ye, Tinghong; Lin, Ziqiang; Sang, Yaxiong; Su, Chao; Wan, Yang; Shen, Guobo; Ma, Xuelei; Yu, Min; Guo, Fuchun; Liu, Yanyang; Li, Ling; Hu, Qiancheng; Wang, Yongsheng; Wei, Yuquan

2015-01-01

Hemorrhage is a common clinical manifestation in patients with cancer. Intratumor hemorrhage has been demonstrated to be a poor prognostic factor for cancer patients. In this study, we investigated the role of RBCs and hemoglobin (Hb) in the process of tumor progression and therapeutical response. RBCs and Hb potently promoted tumor cell proliferation and syngenic tumor growth. RBCs and Hb activated the reactive oxygen species-NF-κB pathway in both tumor cells and macrophages. RBCs and Hb also induced chemoresistance mediated, in part, by upregulating ABCB1 gene expression. Tumor growth induced by RBCs was accompanied by an inflammatory signature, increased tumor vasculature, and influx of M2 macrophages. In both the peritoneal cavity and tumor microenvironment, extravascular RBCs rapidly recruited monocyte-macrophages into the lesion sites. In addition, RBCs and Hb increased several nucleotide-binding oligomerization domain-like receptors' expression and induced IL-1β release. Our results provide novel insights into the protumor function of RBCs and Hb as endogenous danger signals, which can promote tumor cell proliferation, macrophage recruitment, and polarization. Hemorrhage may represent a useful prognostic factor for cancer patients because of its role in tumor promotion and chemoresistance. Copyright © 2014 by The American Association of Immunologists, Inc.

Headaches - danger signs

Science.gov (United States)

Migraine headache - danger signs; Tension headache - danger signs; Cluster headache - danger signs; Vascular headache - danger signs ... and other head pain. In: Goldman L, Schafer AI, eds. Goldman-Cecil Medicine . 25th ed. Philadelphia, PA: ...

Using an Activity to Simulate the Dangers of Multitasking with Technology while Walking

Science.gov (United States)

Lazaros, Edward J.; Xu, Renmei; Londt, Susan

2012-01-01

People are increasingly trying to multitask while walking. Text messaging while walking is a significant area for concern. The number of text messages sent is expected to be more than 8 trillion in 2012. Texting is becoming so commonplace that people use this technology while engaged in other activities. The dangers of multitasking have hit the…

8. knowledge and perception of women towards danger signs

African Journals Online (AJOL)

Esem

Sometimes a pregnant woman may experience signs and symptoms which signal danger. ... order to raise women's awareness and enable them to seek care when they .... midwifery students graduate with the skills to teach women and ...

Contesting danger

DEFF Research Database (Denmark)

Heathershaw, John; Megoran, Nick

2011-01-01

and subsequent considerations of the region in terms of the war on terror. It considers several examples of this discourse of danger including the popular US TV drama about presidential politics, The West Wing, the policy texts of ‘Washingtonian security analysis’ and accounts of danger, insecurity and urban...... of danger is contested within the region. The example of urban violence in Osh, Kyrgyzstan and Jalalabad, Afghanistan in 2010 demonstrates how opportunities to mitigate conflict may have been lost due to the distortions of this discourse of danger. It concludes by raising the challenge to policy...

Warning Signals or Dangerous Opportunities? Globalization, Gender, and Educational Policy Shifts.

Science.gov (United States)

Blackmore, Jill

2000-01-01

Examines the relationship between education and globalization through the lenses of feminist theories, discussing the consequences of globalization for gender equity work in education. The paper argues that the restructuring of the government that flows from the neoliberal political response to globalization presents dangerous opportunities for…

Metabolic features of the cell danger response.

Science.gov (United States)

Naviaux, Robert K

2014-05-01

The cell danger response (CDR) is the evolutionarily conserved metabolic response that protects cells and hosts from harm. It is triggered by encounters with chemical, physical, or biological threats that exceed the cellular capacity for homeostasis. The resulting metabolic mismatch between available resources and functional capacity produces a cascade of changes in cellular electron flow, oxygen consumption, redox, membrane fluidity, lipid dynamics, bioenergetics, carbon and sulfur resource allocation, protein folding and aggregation, vitamin availability, metal homeostasis, indole, pterin, 1-carbon and polyamine metabolism, and polymer formation. The first wave of danger signals consists of the release of metabolic intermediates like ATP and ADP, Krebs cycle intermediates, oxygen, and reactive oxygen species (ROS), and is sustained by purinergic signaling. After the danger has been eliminated or neutralized, a choreographed sequence of anti-inflammatory and regenerative pathways is activated to reverse the CDR and to heal. When the CDR persists abnormally, whole body metabolism and the gut microbiome are disturbed, the collective performance of multiple organ systems is impaired, behavior is changed, and chronic disease results. Metabolic memory of past stress encounters is stored in the form of altered mitochondrial and cellular macromolecule content, resulting in an increase in functional reserve capacity through a process known as mitocellular hormesis. The systemic form of the CDR, and its magnified form, the purinergic life-threat response (PLTR), are under direct control by ancient pathways in the brain that are ultimately coordinated by centers in the brainstem. Chemosensory integration of whole body metabolism occurs in the brainstem and is a prerequisite for normal brain, motor, vestibular, sensory, social, and speech development. An understanding of the CDR permits us to reframe old concepts of pathogenesis for a broad array of chronic, developmental

Decree 2211: Standards to control the generation and handling of dangerous wastes

International Nuclear Information System (INIS)

1992-01-01

This Decree has for object to establish the conditions under which should be carried out the activities of generation and handling of dangerous waste, in order to prevent damages to health and to the atmosphere. It includes: definitions; a list of sources of waste; a list of constituent of dangerous waste; the characteristics of danger; a lists of maximum permissible concentrations in leachates, handling of dangerous waste, criterion for transport, monitoring form, storage areas, treatment and final disposition, storage, elimination, incineration, recycling, reuse and recovery, installation and operation of security backfilling, book of waste record, control of activities, obligations in charge of those who manage dangerous waste, and trans border movements of dangerous waste [es

Dangerous and severe personality disorder: an ethical concept?

Science.gov (United States)

Glen, Sally

2005-04-01

Most clinicians and mental health practitioners are reluctant to work with people with dangerous and severe personality disorders because they believe there is nothing that mental health services can offer. Dangerous and severe personality disorder also signals a diagnosis which is problematic morally. Moral philosophy has not found an adequate way of dealing with personality disorders. This paper explores the question: What makes a person morally responsible for his actions and what is a legitimate mitigating factor? How do psychiatric nurses working with this client group understand the awful things some clients do? What concepts do they need, if they are to know how to explain and how to react? It is suggested that dangerous and severe personality disorder is best regarded as a moral category, framed in terms of goodness, badness, obligation and other ethical concepts. It seems plausible that in important ways the dangerous and severe personality disordered client does not understand morality or understands it differently. The peculiar position of the dangerous and severe personality disordered individual in our system of moral responsibility stems from his apparent inability to see the importance of the interests of others. It might be more helpful to regard personality disordered clients as we do children: partially but not fully reasonable for their actions. We might regard the dangerous and severe personality disordered client responsible for those actions which he most clearly understands, such as causing others physical pain, but not for those with which he is only superficially engaged, such as causing emotional pain. The paper concludes by suggesting that the dangerous and severe personality disordered individual does not fit easily into any conventional moral category, be it criminal, patient, animal or child, and thus an assessment of his moral accountability must take into consideration his special circumstances.

Forest fire danger index based on modifying Nesterov Index, fuel, and anthropogenic activities using MODIS TERRA, AQUA and TRMM satellite datasets

Science.gov (United States)

Suresh Babu, K. V.; Roy, Arijit; Ramachandra Prasad, P.

2016-05-01

Forest fire has been regarded as one of the major causes of degradation of Himalayan forests in Uttarakhand. Forest fires occur annually in more than 50% of forests in Uttarakhand state, mostly due to anthropogenic activities and spreads due to moisture conditions and type of forest fuels. Empirical drought indices such as Keetch-Byram drought index, the Nesterov index, Modified Nesterov index, the Zhdanko index which belongs to the cumulative type and the Angstrom Index which belongs to the daily type have been used throughout the world to assess the potential fire danger. In this study, the forest fire danger index has been developed from slightly modified Nesterov index, fuel and anthropogenic activities. Datasets such as MODIS TERRA Land Surface Temperature and emissivity (MOD11A1), MODIS AQUA Atmospheric profile product (MYD07) have been used to determine the dew point temperature and land surface temperature. Precipitation coefficient has been computed from Tropical Rainfall measuring Mission (TRMM) product (3B42RT). Nesterov index has been slightly modified according to the Indian context and computed using land surface temperature, dew point temperature and precipitation coefficient. Fuel type danger index has been derived from forest type map of ISRO based on historical fire location information and disturbance danger index has been derived from disturbance map of ISRO. Finally, forest fire danger index has been developed from the above mentioned indices and MODIS Thermal anomaly product (MOD14) has been used for validating the forest fire danger index.

Keep away from danger: Dangerous objects in dynamic and static situations

Directory of Open Access Journals (Sweden)

Filomena eAnelli

2013-07-01

Full Text Available Behavioral and neuroscience studies have shown that objects observation evokes specific affordances (i.e., action possibilities and motor responses. Recent findings provide evidence that even dangerous objects can modulate the motor system evoking aversive affordances. This sounds intriguing since so far the majority of behavioral, brain imaging, and transcranial magnetic stimulation studies with painful and dangerous stimuli strictly concerned the domain of pain, excepted for evidence suggesting sensitivity to objects’ affordances when neutral objects are located in participants’ peripersonal space. This study investigates whether the observation of a neutral or dangerous object in a static or dynamic situation differently influences motor responses, and the time-course of the dangerous objects’ processing. In three experiments we manipulated: object dangerousness (neutral vs. dangerous; object category (artifact vs. natural; manual response typology (press vs. release a key; object presentation (Experiment 1: dynamic, Experiments 2 and 3: static; object movement direction (Experiment 1: away vs. toward the participant or size (Experiments 2 and 3: big vs. normal vs. small. The task required participants to decide whether the object was an artifact or a natural object, by pressing or releasing one key. Results showed a facilitation for neutral over dangerous objects in the static situation, probably due to an affordance effect. Instead, in the dynamic condition responses were modulated by the object movement direction, with a dynamic affordance effect of neutral objects and an escape-avoidance effect of dangerous objects (neutral objects were processed faster when they moved toward-approached the participant, whereas dangerous objects were processed faster when they moved away from the participant. Moreover, static stimuli influenced the manual response typology. These data indicate the emergence of dynamic affordance and escaping

Innate immunity and the sensing of infection, damage and danger in the female genital tract.

Science.gov (United States)

Sheldon, Iain Martin; Owens, Siân-Eleri; Turner, Matthew Lloyd

2017-02-01

Tissue homeostasis in the female genital tract is challenged by infection, damage, and even physiological events during reproductive cycles. We propose that the evolutionarily ancient system of innate immunity is sufficient to sense and respond to danger in the non-pregnant female genital tract. Innate immunity produces a rapidly inducible, non-specific response when cells sense danger. Here we provide a primer on innate immunity and discuss what is known about how danger signals are sensed in the endometrium and ovary, the impact of inflammatory responses on reproduction, and how endocrinology and innate immunity are integrated. Endometrial epithelial and stromal cells, and ovarian granulosa cells express pattern recognition receptors, similar to cells of the innate immune system. These pattern recognition receptors, such as the Toll-like receptors, bind pathogen-associated or damage-associated molecular patterns. Activation of pattern recognition receptors leads to inflammation, recruitment of immune cells from the peripheral circulation, and phagocytosis. Although the inflammatory response helps maintain or restore endometrial health, there may also be negative consequences for fertility, including perturbation of oocyte competence. The intensity of the inflammatory response reflects the balance between the level of danger and the systems that regulate innate immunity, including the endocrine environment. Understanding innate immunity is important because disease and inappropriate inflammatory responses in the endometrium or ovary cause infertility. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The dangers of irradiate uranium in nuclear reactors; Les dangers de l'uranium irradie dans les reacteurs nucleaires

Energy Technology Data Exchange (ETDEWEB)

Jammet, H; Joffre, H [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

1955-07-01

The danger of the uranium cans sur-activated by the use in the nuclear reactors is triple: - Irradiation from afar, during manipulations of the cans. - Contamination of air when decladding. - Contamination of air by fire of uranium in a reactor in function The first two dangers are usual and can be treated thanks to the rules of security in use in the atomic industry. The third has an accidental character and claimed for the use of special and exceptional rules, overflowing the industrial setting, to reach the surrounding populations. (authors) [French] Le danger des cartouches d'uranium suractive par utilisation dans les reacteurs nucleaires est triple: - Irradiation a distance, lors des manipulations des cartouches. - Contamination de l'air au moment de leur degainage. - Contamination de l'air par incendie d'uranium dans un reacteur en fonctionnement. Les deux premiers dangers sont habituels et peuvent etre traites grace aux regles de securite en usage dans l'industrie atomique. Le troisieme revet un caractere accidentel et reclame l'emploi de regles speciales et exceptionnelles, debordant le cadre industriel, pour atteindre celui des populations environnantes. (auteurs)

The heterosexual singles scene: putting danger into pleasure.

Science.gov (United States)

Peart, R; Rosenthal, D; Moore, S

1996-06-01

The juxtaposition of pleasure and danger has engaged many feminist theorists and researchers in the field of sexuality. This article presents a theoretical analysis of the ambiguous and complex relationship between 'pleasure', 'danger' and contemporary feminist theory. In doing so, it offers an understanding of the ways in which the categories of pleasure and danger operate within the discourses of heterosexuality to construct perceptions of risk in the context of HIV/AIDS. Data were collected from a study of the sexual attitudes and practices of 112 sexually-active, single, heterosexual adults (58 men and 54 women), aged 20 to 40 years (mean = 27 years) who agreed to be interviewed when approached at night-clubs and public "singles' bars around Melbourne, Australia. The qualitative analysis presented here is consistent with a poststructuralist feminism. First, we discuss how sexuality cannot be cast solely as pleasurable or dangerous. Second, we demonstrate how heterosexualized notions of pleasure and danger operate to provide misperceptions of risk from HIV/AIDS transmission. Third, we identify the ways in which the logic of identity functions to obscure risk within the discourse of heterosexuality, and finally we attempt to forge new ways of practising pleasure which disrupt heterosexist discourses and allow for pleasures which incorporate danger.

Ca 2+ signaling by plant Arabidopsis thaliana Pep peptides depends on AtPepR1, a receptor with guanylyl cyclase activity, and cGMP-activated Ca 2+ channels

KAUST Repository

Qia, Zhi

2010-11-18

A family of peptide signaling molecules (AtPeps) and their plasma membrane receptor AtPepR1 are known to act in pathogendefense signaling cascades in plants. Little is currently known about the molecular mechanisms that link these signaling peptides and their receptor, a leucine-rich repeat receptor-like kinase, to downstream pathogen-defense responses. We identify some cellular activities of these molecules that provide the context for a model for their action in signaling cascades. AtPeps activate plasma membrane inwardly conducting Ca 2+ permeable channels in mesophyll cells, resulting in cytosolic Ca 2+ elevation. This activity is dependent on their receptor as well as a cyclic nucleotide-gated channel (CNGC2). We also show that the leucine-rich repeat receptor- like kinase receptor AtPepR1 has guanylyl cyclase activity, generating cGMP from GTP, and that cGMP can activate CNGC2- dependent cytosolic Ca 2+ elevation. AtPep-dependent expression of pathogen-defense genes (PDF1.2, MPK3, and WRKY33) is mediated by the Ca 2+ signaling pathway associated with AtPep peptides and their receptor. The work presented here indicates that extracellular AtPeps, which can act as danger-associated molecular patterns, signal by interaction with their receptor, AtPepR1, a plasma membrane protein that can generate cGMP. Downstream from AtPep and AtPepR1 in a signaling cascade, the cGMP-activated channel CNGC2 is involved in AtPep- and AtPepR1-dependent inward Ca 2+ conductance and resulting cytosolic Ca 2+ elevation. The signaling cascade initiated by AtPeps leads to expression of pathogen- defense genes in a Ca 2+-dependent manner.

Genetic Markers and Danger Signals in Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis

Directory of Open Access Journals (Sweden)

Wen-Hung Chung

2010-01-01

Full Text Available Stevens-Johnson syndrome (SJS and toxic epidermal necrolysis (TEN are life-threatening adverse reactions, which could be induced by a variety of drugs. It was proposed that human leukocyte antigen (HLA-restricted presentation of antigens (drugs or their metabolites to T lymphocytes initiates the immune reactions of SJS/ TEN. However, the genetic susceptibility and the exact pathogenesis were not clear until the recent studies. We first identified that HLA-B*1502 is strongly associated with carbamazepine (CBZ-induced SJS/TEN and HLA-B*5801 with allopurinol-SJS/TEN in Han Chinese. The same associations had been validated across different human populations. For the downstream danger signals, Fas-Fas ligand (FasL and perforin/granzyme B had been advocated as cytotoxic mediators for keratinocyte death in SJS/TEN. However, expression levels of these cytotoxic proteins from the skin lesions were too low to explain the distinct and extensive epidermal necrosis. Our recent study identified that the granulysin, a cytotoxic protein released from cytotoxic T cells or natural killer (NK cells, is a key mediator for disseminated keratinocyte death in SJS/TEN. This article aims to provide an overview of both of the genomic and immunologic perspectives of SJS/TEN. These studies give us a better understanding of the immune mechanisms, biomarkers for disease prevention and early diagnosis, as well as providing the therapeutic targets for the treatments of SJS/TEN.

Use of the theory of recognition of patterns in developing methane metering equipment for blow-out-dangerous mines. [Instrument recognizes rate of change of methane concentration and, if dangerous, shuts off electrical equipment

Energy Technology Data Exchange (ETDEWEB)

Medvedev, V N

1978-01-01

In the most general form, the existing methane-metering equipment which issues command signals when the maximum permissible value of methane concentration has been reached can be viewed as a recognition system. The algorithm for operation on the principle of evaluating the degree of blow-out danger of the ore atmosphere stipulates the recognition of two situations: 1) ''not dangerous ''(methane concentration below maximum permissible value); 2) ''dangerous'' (disorders in technological process; methane concentration above maximum permissible value). This approach for constructing means for gas protection is optimal only for mines working beds which are not dangerous for sudden blow-outs. However, if we ''train'' the apparatus to recognize what was the reason for increase in methane concentration, ways are afforded for solving the problem of creating an effective methane-metering equipment for mines with sudden blow-outs. Gas-dynamic processes with sudden blow-outs can be distinguished from standard technological, in particular, according to the rate in increase in methane concentration. On this basis, functional plan is proposed for constructing the automatic gas protection for explosiondangerous mines which includes a primary measurement of methane concentration, block of concentration control, block of process recognition, block of command signals, block of information delay, block of measuring the rate of methane concentration, threshold device for the rate of increase in concentration.

Does Pedestrian Danger Mediate the Relationship between Local Walkability and Active Travel to Work?

Directory of Open Access Journals (Sweden)

Sandy J Slater

2016-05-01

Full Text Available Background: Environmental and policy factors play an important role in influencing people’s lifestyles, physical activity (PA, and risks for developing obesity. Research suggests that more walkable communities are needed to sustain lifelong PA behavior, but there is a need to determine what local built environment features facilitate making being active the easy choice.Purpose: This county-level study examined the association between local walkability (walkability and traffic calming scales, pedestrian danger, and the percent of adults who used active transport to work. Methods: Built environment and PA outcome measures were constructed for the 496 most populous counties representing 74 percent of the U.S. population. GIS-based walkability scales were constructed and include a census of roads located within the counties using 2011 Navteq data. The pedestrian danger index (PDI includes data collected from the Fatality Analysis Reporting System 2009-2011, and measures the likelihood of a pedestrian being hit and killed by a vehicle. Four continuous outcome measures were constructed using 2009-2013 American Community Survey county-level 5-year estimates. The measures represent the percentage of workers living in a county who worked away from home and: 1 walked to work; 2 biked to work; 3 took public transit; and 4 used any form of active transport. Linear regression and mediation analyses were conducted to examine the association between walkability, PDI and active transport. Models accounted for clustering within state with robust standard errors, and controlled for median household income, families with children in poverty, race, ethnicity, urbanicity and region.Results: The walkability scale was significantly negatively associated with the PDI (β=-0.06, 95% CI=-0.111, -0.002. In all models, the PDI was significantly negatively associated with all active travel-related outcomes at the p<0.01 level. The walkability scale was positively

Does Pedestrian Danger Mediate the Relationship between Local Walkability and Active Travel to Work?

Science.gov (United States)

Slater, Sandy J; Nicholson, Lisa; Abu Zayd, Haytham; Chriqui, Jamie Friedman

2016-01-01

Environmental and policy factors play an important role in influencing people's lifestyles, physical activity (PA), and risks for developing obesity. Research suggests that more walkable communities are needed to sustain lifelong PA behavior, but there is a need to determine what local built environment features facilitate making being active the easy choice. This county-level study examined the association between local walkability (walkability and traffic calming scales), pedestrian danger, and the percent of adults who used active transport to work. Built environment and PA outcome measures were constructed for the 496 most populous counties representing 74% of the U.S. population. Geographic information system-based walkability scales were constructed and include a census of roads located within the counties using 2011 Navteq data. The pedestrian danger index (PDI) includes data collected from the Fatality Analysis Reporting System 2009-2011, and measures the likelihood of a pedestrian being hit and killed by a vehicle. Four continuous outcome measures were constructed using 2009-2013 American Community Survey county-level 5-year estimates. The measures represent the percentage of workers living in a county who worked away from home and (1) walked to work; (2) biked to work; (3) took public transit; and (4) used any form of active transport. Linear regression and mediation analyses were conducted to examine the association between walkability, PDI, and active transport. Models accounted for clustering within state with robust SEs, and controlled for median household income, families with children in poverty, race, ethnicity, urbanicity, and region. The walkability scale was significantly negatively associated with the PDI (β = -0.06, 95% CI = -0.111, -0.002). In all models, the PDI was significantly negatively associated with all active travel-related outcomes at the p walkability scale was positively associated with all four outcomes at the p�

616 Nonradioactive Dangerous Waste Storage Facility dangerous waste permit application

International Nuclear Information System (INIS)

1991-10-01

The 616 Nonradioactive Dangerous Waste Storage Facility Dangerous Waste Permit Application consists of both a Part A and a Part B permit application. An explanation of the Part A revisions associated with this storage unit, including the Part A included with this document, is provided at the beginning of the Part A Section. The Part B consists of 15 chapters addressing the organization and content of the Part B Checklist prepared by the Washington State Department of Ecology (Ecology 1987). For ease of reference, the checklist section numbers, in brackets, follow chapter headings and subheadings. The 616 Nonradioactive Dangerous Waste Storage Facility Dangerous Waste Permit Application (Revision 0) was submitted to the Washington State Department of Ecology and the US Environmental Protection Agency on July 31, 1989. Revision 1, addressing Washington State Department of Ecology review comments made on Revision 0 dated November 21, 1989, and March 23, 1990, was submitted on June 22, 1990. This submittal, Revision 2, addresses Washington State Department of Ecology review comments made on Revision 1, dated June 22, 1990, August 30, 1990, December 18, 1990, and July 8, 1991

Quantitative comparison of fire danger index performance using fire activity

CSIR Research Space (South Africa)

Steenkamp, KC

2012-07-01

Full Text Available parameters such as flame length or rate of spread can be physically measured or modeled. Fire danger indices are not designed to describe the characteristics of a fire but rather the potential of a fire taking place in an area of interest [5]. Several...

PFP dangerous waste training plan

International Nuclear Information System (INIS)

Khojandi, J.

1996-01-01

This document establishes the minimum training requirements for the Plutonium Finishing Plant (PFP) personnel who are responsible for management of dangerous waste. The training plan outlines training requirements for handling of solid dangerous waste during generator accumulation and liquid dangerous waste during treatment and storage operations. The implementation of this training plan will ensure the PFP facility compliance with the training plan requirements of Dangerous Waste Regulation. Chapter 173-303-330. Washington Administrative Code (WAC). The requirements for such compliance is described in Section 11.0 of WHC-CM-7-5 Environmental Compliance Manual

A new website with real-time dissemination of information on fire activity and meteorological fire danger in Portugal

Science.gov (United States)

DaCamara, Carlos; Trigo, Ricardo; Nunes, Sílvia; Pinto, Miguel; Oliveira, Tiago; Almeida, Rui

2017-04-01

In Portugal, like in Mediterranean Europe, fire activity is a natural phenomenon linking climate, humans and vegetation and is therefore conditioned by natural and anthropogenic factors. Natural factors include topography, vegetation cover and prevailing weather conditions whereas anthropogenic factors encompass land management practices and fire prevention policies. Land management practices, in particular the inadequate use of fire, is a crucial anthropogenic factor that accounts for about 90% of fire ignitions. Fire prevention policies require adequate and timely information about wildfire potential assessment, which is usually based on fire danger rating systems that provide indices to be used on an operational and tactical basis in decision support systems. We present a new website designed to provide the user community with relevant real-time information on fire activity and meteorological fire danger that will allow adopting the adequate measures to mitigate fire damage. The fire danger product consists of forecasts of fire danger over Portugal based on a statistical procedure that combines information about fire history derived from the Fire Radiative Power product disseminated by the Land Surface Analysis Satellite Application Facility (LSA SAF) with daily meteorological forecasts provided by the European Centre for Medium-Range Weather Forecasts (ECMWF). The aim of the website is fourfold; 1) to concentrate all information available (databases and maps) relevant to fire management in a unique platform so that access by end users becomes easier, faster and friendlier; 2) to supervise the access of users to the different products available; 3) to control and assist the access to the platform and obtain feedbacks from users for further improvements; 4) to outreach the operational community and foster the use of better information that increase efficiency in risk management. The website is sponsored by The Navigator Company, a leading force in the global pulp

The Clinical Prediction of Dangerousness.

Science.gov (United States)

1985-05-01

8217 8 ings. Szasz (1963) has argued persuasively that clinical predictions of future dangerous behavior are unfairly focused on the mentally ill...Persons labeled paranoid, Szasz states, are readily commitable, while highly dangerous drunken drivers are not. Indeed, dangerousness such as that...Psychology, 31, 492-494. Szasz , T. (1963). Law, liberty and psychiatry. New York: Macmillan. Taft, R. (1955). The ability to judge people. Psychological

Plant signalling: the opportunities and dangers of chemical communication.

Science.gov (United States)

Adler, Frederick R

2011-04-23

The notion of chemical communication between plants and other organisms has gone from being viewed as a fringe idea to an accepted ecological phenomenon only recently. An Organized Oral Session at the August 2010 Ecological Society of America meeting in Pittsburgh examined the role of plant signalling both within and between plants, with speakers addressing the remarkably wide array of effects that plant signals have on plant physiology, species interactions and entire communities. In addition to the familiar way that plants communicate with mutualists like pollinators and fruit dispersers through both chemical and visual cues, speakers at this session described how plants communicate with themselves, with each other, with herbivores and with predators of those herbivores. These plant signals create a complex odour web superimposed upon the more classical food web itself, with its own dynamics in the face of exotic species and rapid community assembly and disassembly.

Overcoming negative tendencies concerning public attitude to potentially dangerous technologies

International Nuclear Information System (INIS)

Barinov, A.; Shmelev, S.

1995-01-01

The Moscow Scientific industrial Association RADON is an enterprise with potentially dangerous technology. RADON fulfils the collection, transportation, treatment and disposal of radioactive waste from Moscow region. The inhabitants of this region consider it, and that is true, to be essentially dangerous. We understood, that it is necessary to change the situation and give the public the true information about RADON's activity. For this purpose 4 years ago we developed a new Department, the Department or External Relations

Danger and usefulness: an alternative framework for understanding rapid evaluation effects in perception?

Science.gov (United States)

Wurm, Lee H

2007-12-01

Previous studies have shown effects of rated danger and usefulness on lexical access. All of them have used stimuli selected for connotations of danger and/or usefulness. Stimuli for the present lexical decision study were all of the nouns, verbs, and adjectives from the Balota et al. (2002) English Lexicon Project (subject to constraints relating to experimental control; none had anything to do with danger or usefulness). The interaction between danger and usefulness ratings previously demonstrated (Wurm & Vakoch, 2000; Wurm, Vakoch, Seaman, & Buchanan, 2004; Wurm, Whitman, Seaman, Hill, & Ulstad, 2007) was found for nouns, even when age of acquisition was controlled. It was also found for verbs and adjectives. The interaction is believed to reflect competing pressures to (1) avoid dangerous objects/events and (2) approach valuable resources. It may be a manifestation of the rapid evaluation effects pervasive in the literature. Post hoc analyses showed that danger and usefulness explain as much variance as valence and arousal, or evaluation, potency, and activity.

STAT3 Activities and Energy Metabolism: Dangerous Liaisons

Energy Technology Data Exchange (ETDEWEB)

Camporeale, Annalisa, E-mail: annalisa.camporeale@unito.it [Molecular Biotechnology Center and Department of Molecular Biotechnology and Life Sciences, University of Turin, Via Nizza 52, Turin 10126 (Italy); Demaria, Marco [Buck Institute for Research on Aging, 8001 Redwood Blvd, Novato, CA 94945 (United States); Monteleone, Emanuele [Molecular Biotechnology Center and Department of Molecular Biotechnology and Life Sciences, University of Turin, Via Nizza 52, Turin 10126 (Italy); Giorgi, Carlotta [Department of Experimental and Diagnostic Medicine, Section of General Pathology, Laboratory for Technologies of Advances Therapies (LTTA), University of Ferrara, Via Fossato di Mortara 70, Ferrara 44121 (Italy); Wieckowski, Mariusz R. [Nencki Institute of Experimental Biology, Department of Biochemistry, Pasteur Str. 3, Warsaw 02-093 (Poland); Pinton, Paolo [Department of Experimental and Diagnostic Medicine, Section of General Pathology, Laboratory for Technologies of Advances Therapies (LTTA), University of Ferrara, Via Fossato di Mortara 70, Ferrara 44121 (Italy); Poli, Valeria, E-mail: annalisa.camporeale@unito.it [Molecular Biotechnology Center and Department of Molecular Biotechnology and Life Sciences, University of Turin, Via Nizza 52, Turin 10126 (Italy)

2014-07-31

STAT3 mediates cytokine and growth factor receptor signalling, becoming transcriptionally active upon tyrosine 705 phosphorylation (Y-P). Constitutively Y-P STAT3 is observed in many tumors that become addicted to its activity, and STAT3 transcriptional activation is required for tumor transformation downstream of several oncogenes. We have recently demonstrated that constitutively active STAT3 drives a metabolic switch towards aerobic glycolysis through the transcriptional induction of Hif-1α and the down-regulation of mitochondrial activity, in both MEF cells expressing constitutively active STAT3 (Stat3{sup C/C}) and STAT3-addicted tumor cells. This novel metabolic function is likely involved in mediating pre-oncogenic features in the primary Stat3{sup C/C} MEFs such as resistance to apoptosis and senescence and rapid proliferation. Moreover, it strongly contributes to the ability of primary Stat3{sup C/C} MEFs to undergo malignant transformation upon spontaneous immortalization, a feature that may explain the well known causative link between STAT3 constitutive activity and tumor transformation under chronic inflammatory conditions. Taken together with the recently uncovered role of STAT3 in regulating energy metabolism from within the mitochondrion when phosphorylated on Ser 727, these data place STAT3 at the center of a hub regulating energy metabolism under different conditions, in most cases promoting cell survival, proliferation and malignant transformation even though with distinct mechanisms.

STAT3 Activities and Energy Metabolism: Dangerous Liaisons

International Nuclear Information System (INIS)

Camporeale, Annalisa; Demaria, Marco; Monteleone, Emanuele; Giorgi, Carlotta; Wieckowski, Mariusz R.; Pinton, Paolo; Poli, Valeria

2014-01-01

STAT3 mediates cytokine and growth factor receptor signalling, becoming transcriptionally active upon tyrosine 705 phosphorylation (Y-P). Constitutively Y-P STAT3 is observed in many tumors that become addicted to its activity, and STAT3 transcriptional activation is required for tumor transformation downstream of several oncogenes. We have recently demonstrated that constitutively active STAT3 drives a metabolic switch towards aerobic glycolysis through the transcriptional induction of Hif-1α and the down-regulation of mitochondrial activity, in both MEF cells expressing constitutively active STAT3 (Stat3 C/C ) and STAT3-addicted tumor cells. This novel metabolic function is likely involved in mediating pre-oncogenic features in the primary Stat3 C/C MEFs such as resistance to apoptosis and senescence and rapid proliferation. Moreover, it strongly contributes to the ability of primary Stat3 C/C MEFs to undergo malignant transformation upon spontaneous immortalization, a feature that may explain the well known causative link between STAT3 constitutive activity and tumor transformation under chronic inflammatory conditions. Taken together with the recently uncovered role of STAT3 in regulating energy metabolism from within the mitochondrion when phosphorylated on Ser 727, these data place STAT3 at the center of a hub regulating energy metabolism under different conditions, in most cases promoting cell survival, proliferation and malignant transformation even though with distinct mechanisms

Negativity Bias in Dangerous Drivers.

Directory of Open Access Journals (Sweden)

Jing Chai

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

The choking game and YouTube: a dangerous combination.

Science.gov (United States)

Linkletter, Martha; Gordon, Kevin; Dooley, Joe

2010-03-01

To study postings of partial asphyxiation by adolescents on YouTube and to increase awareness of this dangerous activity as well as the value of YouTube as a research tool. Videos were searched on YouTube using many terms for recreational partial asphyxiation. Data were gathered on the participants and on the occurrence of hypoxic seizure. Sixty-five videos of the asphyxiation game were identified. Most (90%) participants were male. A variety of techniques were used. Hypoxic seizures were witnessed in 55% of videos, but occurred in 88% of videos that employed the "sleeper hold" technique. The videos were collectively viewed 173550 times on YouTube. YouTube has enabled millions of young people to watch videos of the "choking game" and other dangerous activities. Seeing videos may normalize the behavior among adolescents. Increased awareness of this activity may prevent some youths from participating and potentially harming themselves or others.

Honey Bee Inhibitory Signaling Is Tuned to Threat Severity and Can Act as a Colony Alarm Signal.

Science.gov (United States)

Tan, Ken; Dong, Shihao; Li, Xinyu; Liu, Xiwen; Wang, Chao; Li, Jianjun; Nieh, James C

2016-03-01

Alarm communication is a key adaptation that helps social groups resist predation and rally defenses. In Asia, the world's largest hornet, Vespa mandarinia, and the smaller hornet, Vespa velutina, prey upon foragers and nests of the Asian honey bee, Apis cerana. We attacked foragers and colony nest entrances with these predators and provide the first evidence, in social insects, of an alarm signal that encodes graded danger and attack context. We show that, like Apis mellifera, A. cerana possesses a vibrational "stop signal," which can be triggered by predator attacks upon foragers and inhibits waggle dancing. Large hornet attacks were more dangerous and resulted in higher bee mortality. Per attack at the colony level, large hornets elicited more stop signals than small hornets. Unexpectedly, stop signals elicited by large hornets (SS large hornet) had a significantly higher vibrational fundamental frequency than those elicited by small hornets (SS small hornet) and were more effective at inhibiting waggle dancing. Stop signals resulting from attacks upon the nest entrance (SS nest) were produced by foragers and guards and were significantly longer in pulse duration than stop signals elicited by attacks upon foragers (SS forager). Unlike SS forager, SS nest were targeted at dancing and non-dancing foragers and had the common effect, tuned to hornet threat level, of inhibiting bee departures from the safe interior of the nest. Meanwhile, nest defenders were triggered by the bee alarm pheromone and live hornet presence to heat-ball the hornet. In A. cerana, sophisticated recruitment communication that encodes food location, the waggle dance, is therefore matched with an inhibitory/alarm signal that encodes information about the context of danger and its threat level.

46 CFR 5.35 - Conviction for a dangerous drug law violation, use of, or addiction to the use of dangerous drugs.

Science.gov (United States)

2010-10-01

..., or addiction to the use of dangerous drugs. 5.35 Section 5.35 Shipping COAST GUARD, DEPARTMENT OF... Definitions § 5.35 Conviction for a dangerous drug law violation, use of, or addiction to the use of dangerous... complaint will allege conviction for a dangerous drug law violation or use of dangerous drugs or addiction...

Are College Students' Assessments of Threat Shaped by the Dangers of Their Childhood Environment?

Science.gov (United States)

Sherman, Amanda K; Minich, Steven H; Langen, Tom A; Skufca, Joseph; Wilke, Andreas

2016-07-01

Humans internalize environmental cues of mortality risk at an early age, which influences subsequent risk perceptions and behavior. In this respect, an individual's current risk assessment may be viewed as an adaptive response to the dangers present within his or her early local environment. Here we examine the relationship between several variables indicating threat within an individual's early environment (e.g., prevalence of violent and property crimes, registered sex offenders) and their perception of crime risk within both the childhood and current adult environments. We recruited a group of 657 students who hail from diverse geographic backgrounds to provide the zip code location of their childhood residence along with subjective ratings of danger of that and their current location, which enabled us to compare their ratings of risk/danger with the federally reported crime statistics of each setting. Our results indicate that the early prevalence of registered sex offenders indeed influences an individual's risk perception in adulthood, and that these factors have a differential effect on males and females. Our findings provide support for the theory that early environmental factors signaling danger affect how individuals assess risk within their adult environment. © The Author(s) 2015.

TRACKING AND TRACING SOLUTION FOR DANGEROUS GOODS CARRIED BY INTERMODAL TRANSPORT

Directory of Open Access Journals (Sweden)

Marek Kvet

2014-03-01

Full Text Available This paper deals with the problem of designing a complex tracking and tracing solution for dangerous goods transportation with the support of modern information technologies. This research activity presents a part of the “ChemLogTT” [2] project solved at the University of Žilina. The main goal of our contribution is to present basic conception of a complex developed software tool for monitoring and analyzing mentioned dangerous goods transportation.

Honey Bee Inhibitory Signaling Is Tuned to Threat Severity and Can Act as a Colony Alarm Signal.

Directory of Open Access Journals (Sweden)

Ken Tan

2016-03-01

Full Text Available Alarm communication is a key adaptation that helps social groups resist predation and rally defenses. In Asia, the world's largest hornet, Vespa mandarinia, and the smaller hornet, Vespa velutina, prey upon foragers and nests of the Asian honey bee, Apis cerana. We attacked foragers and colony nest entrances with these predators and provide the first evidence, in social insects, of an alarm signal that encodes graded danger and attack context. We show that, like Apis mellifera, A. cerana possesses a vibrational "stop signal," which can be triggered by predator attacks upon foragers and inhibits waggle dancing. Large hornet attacks were more dangerous and resulted in higher bee mortality. Per attack at the colony level, large hornets elicited more stop signals than small hornets. Unexpectedly, stop signals elicited by large hornets (SS large hornet had a significantly higher vibrational fundamental frequency than those elicited by small hornets (SS small hornet and were more effective at inhibiting waggle dancing. Stop signals resulting from attacks upon the nest entrance (SS nest were produced by foragers and guards and were significantly longer in pulse duration than stop signals elicited by attacks upon foragers (SS forager. Unlike SS forager, SS nest were targeted at dancing and non-dancing foragers and had the common effect, tuned to hornet threat level, of inhibiting bee departures from the safe interior of the nest. Meanwhile, nest defenders were triggered by the bee alarm pheromone and live hornet presence to heat-ball the hornet. In A. cerana, sophisticated recruitment communication that encodes food location, the waggle dance, is therefore matched with an inhibitory/alarm signal that encodes information about the context of danger and its threat level.

The relationship of dangerous driving with traffic offenses: A study on an adapted measure of dangerous driving.

Science.gov (United States)

Iliescu, Dragoş; Sârbescu, Paul

2013-03-01

Using data from three different samples and more than 1000 participants, the current study examines differences in dangerous driving in terms of age, gender, professional driving, as well as the relationship of dangerous driving with behavioral indicators (mileage) and criteria (traffic offenses). The study uses an adapted (Romanian) version of the Dula Dangerous Driving Index (DDDI, Dula and Ballard, 2003) and also reports data on the psychometric characteristics of this measure. Findings suggest that the Romanian version of the DDDI has sound psychometric properties. Dangerous driving is higher in males and occasional drivers, is not correlated with mileage and is significantly related with speeding as a traffic offense, both self-reported and objectively measured. The utility of predictive models including dangerous driving is not very large: logistic regression models have a significant fit to the data, but their misclassification rate (especially in terms of sensitivity) is unacceptable high. Copyright © 2012 Elsevier Ltd. All rights reserved.

Dangerous animals capture and maintain attention in humans.

Science.gov (United States)

Yorzinski, Jessica L; Penkunas, Michael J; Platt, Michael L; Coss, Richard G

2014-05-28

Predation is a major source of natural selection on primates and may have shaped attentional processes that allow primates to rapidly detect dangerous animals. Because ancestral humans were subjected to predation, a process that continues at very low frequencies, we examined the visual processes by which men and women detect dangerous animals (snakes and lions). We recorded the eye movements of participants as they detected images of a dangerous animal (target) among arrays of nondangerous animals (distractors) as well as detected images of a nondangerous animal (target) among arrays of dangerous animals (distractors). We found that participants were quicker to locate targets when the targets were dangerous animals compared with nondangerous animals, even when spatial frequency and luminance were controlled. The participants were slower to locate nondangerous targets because they spent more time looking at dangerous distractors, a process known as delayed disengagement, and looked at a larger number of dangerous distractors. These results indicate that dangerous animals capture and maintain attention in humans, suggesting that historical predation has shaped some facets of visual orienting and its underlying neural architecture in modern humans.

The plutonium danger

International Nuclear Information System (INIS)

Ruiter, W. de

1983-01-01

Nobody can ignore the fact that plutonium is potentially very dangerous and the greatest danger concerning it lies in the spreading of nuclear weapons via nuclear energy programmes. The following seven different attitudes towards this problem are presented and discussed: 1) There is no connection between peaceful and military applications; 2) The problem cannot be prevented; 3) A technical solution must be found; 4) plutonium must be totally inaccessible to countries involved in acquiring nuclear weapons; 5) The use of plutonium for energy production should only occur in one multinational centre; 6) Dogmas in the nuclear industry must be enfeebled; 7) All developments in this area should stop. (C.F.)

Nonradioactive Dangerous Waste Landfill supplemental information to the Hanford Facility Contingency Plan (DOE/RL-93-75)

International Nuclear Information System (INIS)

Ingle, S.J.

1996-05-01

This document is a unit-specific contingency plan for the Nonradioactive Dangerous Waste Landfill and is intended to be used as a supplement to DOE/RL-93-75, 'Hanford Facility Contingency Plan.' This unit-specific plan is to be used to demonstrate compliance with the contingency plan requirements of the Washington Administrative Code, Chapter 173-303 for certain Resource, Conservation and Recovery Act of 1976 waste management units. The Nonradioactive Dangerous Waste Landfill (located approximately 3.5 miles southeast of the 200 East Area at the Hanford Site) was used for disposal of nonradioactive dangerous waste from January 1975 to May 1985. Currently, there are no dangerous waste streams disposed in the Nonradioactive Dangerous Waste Landfill. Dangerous waste management activities are no longer required at the landfill. The landfill does not present a significant hazard to adjacent units, personnel, or the environment. It is unlikely that incidents presenting hazards to public health or the environment would occur at the Nonradioactive Dangerous Waste Landfill

[Detection of surface EMG signal using active electrode].

Science.gov (United States)

He, Qinghua; Peng, Chenglin; Wu, Baoming; Wang, He

2003-09-01

Research of surface electromyogram(EMG) signal is important in rehabilitation medicine, sport medicine and clinical diagnosis, accurate detection of signal is the base of quantitative analysis of surface EMG signal. In this article were discussed how to reduce possible noise in the detection of surface EMG. Considerations on the design of electrode unit were presented. Instrumentation amplifier AD620 was employed to design a bipolar active electrode for use in surface EMG detection. The experiments showed that active electrode could be used to improve signal/noise ratio, reduce noise and detect surface EMG signal effectively.

Dangerous Animals Capture and Maintain Attention in Humans

Directory of Open Access Journals (Sweden)

Jessica L. Yorzinski

2014-07-01

Full Text Available Predation is a major source of natural selection on primates and may have shaped attentional processes that allow primates to rapidly detect dangerous animals. Because ancestral humans were subjected to predation, a process that continues at very low frequencies, we examined the visual processes by which men and women detect dangerous animals (snakes and lions. We recorded the eye movements of participants as they detected images of a dangerous animal (target among arrays of nondangerous animals (distractors as well as detected images of a nondangerous animal (target among arrays of dangerous animals (distractors. We found that participants were quicker to locate targets when the targets were dangerous animals compared with nondangerous animals, even when spatial frequency and luminance were controlled. The participants were slower to locate nondangerous targets because they spent more time looking at dangerous distractors, a process known as delayed disengagement, and looked at a larger number of dangerous distractors. These results indicate that dangerous animals capture and maintain attention in humans, suggesting that historical predation has shaped some facets of visual orienting and its underlying neural architecture in modern humans.

Hanford Facility Annual Dangerous Waste Report Calendar Year 2002

International Nuclear Information System (INIS)

FR-EEMAN, D.A.

2003-01-01

Hanford CY 2002 dangerous waste generation and management forms. The Hanford Facility Annual Dangerous Waste Report (ADWR) is prepared to meet the requirements of Washington Administrative Code Sections 173-303-220, Generator Reporting, and 173-303-390, Facility Reporting. In addition, the ADWR is required to meet Hanford Facility RCRA Permit Condition I.E.22, Annual Reporting. The ADWR provides summary information on dangerous waste generation and management activities for the Calendar Year for the Hanford Facility EPA ID number assigned to the Department of Energy for RCRA regulated waste, as well as Washington State only designated waste and radioactive mixed waste. The Solid Waste Information and Tracking System (SWITS) database is utilized to collect and compile the large array of data needed for preparation of this report. Information includes details of waste generated on the Hanford Facility, waste generated offsite and sent to Hanford for management, and other waste management activities conducted at Hanford, including treatment, storage, and disposal. Report details consist of waste descriptions and weights, waste codes and designations, and waste handling codes. In addition, for waste shipped to Hanford for treatment and/or disposal, information on manifest numbers, the waste transporter, the waste receiving facility, and the original waste generators are included. In addition to paper copies, electronic copies of the report are also transmitted to the regulatory agency

Neuronal Functions of Activators of G Protein Signaling

Directory of Open Access Journals (Sweden)

Man K. Tse

2012-05-01

Full Text Available G protein-coupled receptors (GPCRs are one of the most important gateways for signal transduction across the plasma membrane. Over the past decade, several classes of alternative regulators of G protein signaling have been identified and reported to activate the G proteins independent of the GPCRs. One group of such regulators is the activator of G protein signaling (AGS family which comprises of AGS1-10. They have entirely different activation mechanisms for G proteins as compared to the classic model of GPCR-mediated signaling and confer upon cells new avenues of signal transduction. As GPCRs are widely expressed in our nervous system, it is believed that the AGS family plays a major role in modulating the G protein signaling in neurons. In this article, we will review the current knowledge on AGS proteins in relation to their potential roles in neuronal regulations.

2727-S Nonradioactive Dangerous Waste Storage Facility Closure Plan

International Nuclear Information System (INIS)

Wilczek, T.A.; Laws, J.R.; Izatt, R.D.

1992-01-01

This closure plan describes the activities for final closure of the 2727-S Nonradioactive Dangerous Waste Storage (NRDWS) Facility at the Hanford Site. The 2727-S NRDWS Facility provided container storage for nonradioactive dangerous and extremely hazardous wastes generated in the research and development laboratories, process operations, and maintenance and transportation functions throughout the Hanford Site. Storage operations began at the 2727-S NRDWS Facility March 14, 1983, and continued until December 30, 1986, when the last shipment of materials from the facility took place. These storage operations have been moved to the new 616 NRDWS Facility, which is an interim status unit located between the 200 East and 200 West Areas of the Hanford Site

Web-GIS platform for forest fire danger prediction in Ukraine: prospects of RS technologies

Science.gov (United States)

Baranovskiy, N. V.; Zharikova, M. V.

2016-10-01

There are many different statistical and empirical methods of forest fire danger use at present time. All systems have not physical basis. Last decade deterministic-probabilistic method is rapidly developed in Tomsk Polytechnic University. Forest sites classification is one way to estimate forest fire danger. We used this method in present work. Forest fire danger estimation depends on forest vegetation condition, forest fire retrospective, precipitation and air temperature. In fact, we use modified Nesterov Criterion. Lightning activity is under consideration as a high temperature source in present work. We use Web-GIS platform for program realization of this method. The program realization of the fire danger assessment system is the Web-oriented geoinformation system developed by the Django platform in the programming language Python. The GeoDjango framework was used for realization of cartographic functions. We suggest using of Terra/Aqua MODIS products for hot spot monitoring. Typical territory for forest fire danger estimation is Proletarskoe forestry of Kherson region (Ukraine).

Dangers of the vagina.

Science.gov (United States)

Beit-Hallahmi, B

1985-12-01

Beliefs, myths, and literary expressions of men's fear of female genitals are reviewed. Both clinical evidence and folklore provide evidence that men imagine female genitals not only as a source of pleasure and attraction, but also as a source of danger in a very physical sense. The vagina dentata myth has many versions, including some modern ones, and its message is always the same: an awesome danger emanating from a woman's body. The prevalence of such feelings in folklore and in literature is noted.

Regional scales of fire danger rating in the forest: improved technique

Directory of Open Access Journals (Sweden)

A. V. Volokitina

2017-04-01

Full Text Available Wildland fires distribute unevenly in time and over area under the influence of weather and other factors. It is unfeasible to air patrol the whole forest area daily during a fire season as well as to keep all fire suppression forces constantly alert. Daily work and preparedness of forest fire protection services is regulated by the level of fire danger according to weather conditions (Nesterov’s index. PV-1 index, fire hazard class (Melekhov’s scale, regional scales (earlier called local scales. Unfortunately, there is still no unified comparable technique of making regional scales. As a result, it is difficult to maneuver forest fire protection resources, since the techniques currently used are not approved and not tested for their performance. They give fire danger rating incomparable even for neighboring regions. The paper analyzes the state-of-the-art in Russia and abroad. It is stated the irony is that with factors of fire danger measured quantitatively, the fire danger itself as a function has no quantitative expression. Thus, selection of an absolute criteria is of high importance for improvement of daily fire danger rating. On the example of the Chunsky forest ranger station (Krasnoyarsk Krai, an improved technique is suggested of making comparable local scales of forest fire danger rating based on an absolute criterion of fire danger rating – a probable density of active fires per million ha. A method and an algorithm are described of automatized local scales of fire danger that should facilitate effective creation of similar scales for any forest ranger station or aviation regional office using a database on forest fires and weather conditions. The information system of distant monitoring by Federal Forestry Agency of Russia is analyzed for its application in making local scales. To supplement the existing weather station net it is suggested that automatic compact weather stations or, if the latter is not possible, simple

DANGEROUS AND HYPNOTIC DRUG ACT

Science.gov (United States)

Whelan, William M.

1961-01-01

It is unprofessional conduct within the meaning of the Medical Practice Act to prescribe a dangerous drug without either a medical examination by a physician or other medical indications. Dangerous and hypnotic drugs are specifically defined by both state and federal law and distribution is strictly regulated. A physician may administer to his own patients such amounts of dangerous drugs as are necessary for the immediate needs of the patient. The physician may obtain such needed amounts of these drugs by an order placed with a pharmacist marked “for administration to immediate needs of patients.” A licensed physician may also prescribe dangerous and hypnotic drugs for patients and such prescriptions may be refilled on the specific authorization of the physician. A physician who dispenses dangerous and hypnotic drugs to patients must obtain a hypnotic drug license; he must use specific purchase orders when purchasing; the drugs must be labeled in the manner provided by law; and all records of sale shall be open to inspection by authorized officers of the law and kept for three years. By the Principles of Medical Ethics physicians are bound to limit the source of their professional income to medical services actually rendered. Recent decisions of the Judicial Council answer questions concerning a physician's interest in a corporation which purchases, packages and sells medicines under a corporate name. Also answered are questions as to the measures that exist to prevent physicians from abusing the privilege of owning a pharmacy, and whether a physician can ethically rent space in a building owned by him to a pharmacist with a percentage of the income of the pharmacy as rental. The public welfare of California and the nation as determined by legislation strictly regulates the distribution of dangerous drugs. It is in the best interest of the medical profession and its patients that these laws be understood and carefully observed. PMID:13784776

Radiation danger of exclusion zone objects

International Nuclear Information System (INIS)

Kholosha, V.I.; Proskura, N.I.; Ivanov, Yu.A.; Kazakov, S.V.; Arkhipov, A.N.

2001-01-01

The analysis of radiation danger of the Exclusion Zone objects was made. Here, the Zone is defined as the territory from which the population has been evacuated in 1986 owing to the Chernobyl accident and possible outflow of the contaminated substances out of the borders is potentially dangerous to the Ukraine. In the present work were analyzed such problems as sources of radiation danger in the Zone, ways of radionuclide migration out of the borders of the Zone in normal and emergency situations, the non-radiation (ecological) danger factors of the Zone objects, doses (individual and collective) from various sources and on separate ways of their formation, and the characteristics of radiation danger of the Zone objects. The conclusions are: (1) Radionuclide flows both from technologic and natural sources exceed those from Shelter objects, (2) Under emergency conditions, radionuclide flows and doze loading remain comparable with those from emergency sources, (3) To solve some management tasks in radiation situation, the basic works on the Shelter objects should be oriented to decrease probability of emergency occurrence and to reduce radiation influence (prevention wash-outs during high waters, fire-prevention measures in forests and strengthening of the control behind non-authorized use of objects in the Zone). (S. Ohno)

46 CFR 154.1015 - Lighting in gas-dangerous space.

Science.gov (United States)

2010-10-01

... 46 Shipping 5 2010-10-01 2010-10-01 false Lighting in gas-dangerous space. 154.1015 Section 154... Equipment Electrical § 154.1015 Lighting in gas-dangerous space. (a) Each gas-dangerous space that has... protective device for any lighting circuit that is in a gas-dangerous space must open each conductor of the...

Dangerous arachnids-Fake news or reality?

Science.gov (United States)

Hauke, Tobias J; Herzig, Volker

2017-11-01

The public perception of spiders and scorpions is skewed towards the potential harm they can inflict in humans, despite recent scientific evidence that arachnid venom components might be useful as bioinsecticides or even human therapeutics. Nevertheless, arachnids are becoming more popular as pets in Europe, America and Asia, raising the question for regulatory agencies in these regions as to whether they need to take measurements to protect their citizens. In order to decide upon the necessary regulatory steps, they first need to determine which arachnids are actually dangerous to humans. This review therefore provides an overview of the current literature on verified bites and stings from spiders and scorpions with the aim of assessing their potential danger for human health. As a guideline, we also provide a list of those arachnid genera that we consider as potentially dangerous, which includes 10 spider and 11 scorpion genera. The arachnid genera classified as dangerous comprise less than a quarter of all extant scorpion species and only 0.5% of all spiders species, with the actual number most likely being much lower than that, as not all species in those genera might turn out to pose an actual threat for humans. In conclusion, we found that only a small percentage of scorpions and a minute percentage of all spiders can be considered as potentially dangerous to humans. While in some countries of origin the high incidence of envenomations by dangerous arachnids can result in a serious problem to the health system, we assessed the risk that the same species pose when kept as pets under controlled maintenance conditions as significantly lower. Copyright © 2017 Elsevier Ltd. All rights reserved.

Discovery of novel small molecule activators of β-catenin signaling.

Directory of Open Access Journals (Sweden)

Folkert Verkaar

Full Text Available Wnt/β-catenin signaling plays a major role in embryonic development and adult stem cell maintenance. Reduced activation of the Wnt/β-catenin pathway underlies neurodegenerative disorders and aberrations in bone formation. Screening of a small molecule compound library with a β-galactosidase fragment complementation assay measuring β-catenin nuclear entry revealed bona fide activators of β-catenin signaling. The compounds stabilized cytoplasmic β-catenin and activated β-catenin-dependent reporter gene activity. Although the mechanism through which the compounds activate β-catenin signaling has yet to be determined, several key regulators of Wnt/β-catenin signaling, including glycogen synthase kinase 3 and Frizzled receptors, were excluded as the molecular target. The compounds displayed remarkable selectivity, as they only induced β-catenin signaling in a human osteosarcoma U2OS cell line and not in a variety of other cell lines examined. Our data indicate that differences in cellular Wnt/β-catenin signaling machinery can be exploited to identify cell type-specific activators of Wnt/β-catenin signaling.

Cellular Cholesterol Directly Activates Smoothened in Hedgehog Signaling

Energy Technology Data Exchange (ETDEWEB)

Huang, Pengxiang; Nedelcu, Daniel; Watanabe, Miyako; Jao, Cindy; Kim, Youngchang; Liu, Jing; Salic, Adrian

2016-08-01

In vertebrates, sterols are necessary for Hedgehog signaling, a pathway critical in embryogenesis and cancer. Sterols activate the membrane protein Smoothened by binding its extracellular, cysteine-rich domain (CRD). Major unanswered questions concern the nature of the endogenous, activating sterol and the mechanism by which it regulates Smoothened. We report crystal structures of CRD complexed with sterols and alone, revealing that sterols induce a dramatic conformational change of the binding site, which is sufficient for Smoothened activation and is unique among CRD-containing receptors. We demonstrate that Hedgehog signaling requires sterol binding to Smoothened and define key residues for sterol recognition and activity. We also show that cholesterol itself binds and activates Smoothened. Furthermore, the effect of oxysterols is abolished in Smoothened mutants that retain activation by cholesterol and Hedgehog. We propose that the endogenous Smoothened activator is cholesterol, not oxysterols, and that vertebrate Hedgehog signaling controls Smoothened by regulating its access to cholesterol.

Xylitol and Your Dog: Danger, Paws Off

Science.gov (United States)

... Home For Consumers Consumer Updates Xylitol and Your Dog: Danger, Paws Off Share Tweet Linkedin Pin it ... vitamins mouthwash toothpaste Why is Xylitol Dangerous to Dogs, but Not People? In both people and dogs, ...

The risk assesment in storage and transportation of dangerous substances - preoccupations and perspectives

International Nuclear Information System (INIS)

Lazar, Roxana Elena; Dumitrescu, Maria; Stefanescu, Ioan

2001-01-01

The paper presents a risk assessment model for dangerous substance storage and transportation. It will combine also qualitative and quantitative evaluation methods, the results being referred to the lethal risk at individual and social level. The model includes the main tasks to classify the risks and to achieve a scale of priorities. To achieve a proper analysis of a regional risk the following steps should be observed: a list of dangerous substances; the classification of storage and transportation activities in the area; the selection of those activities that can be included in the study; establishing the category of effects ; the estimation of consequences to the environment and people; the calculation of major accidents frequency; the risk level classification. Generally, in the global risk assessment in industrial sector one neglects the risk induced by the transport of dangerous substances. Because of that the decision process in the risk management field can be seriously affected and the initiatives to reduce the risk and to decrease the consequences of potential accidents can be reduced, too. The model will be applied to evaluate the risk due major accidents occurring in the storage of dangerous substances and their transportation on roads, railway or by pipes. It represents a prime action plan at national level to evaluate and analyze the transportation risk. (authors)

knowledge about obstetric danger signs among preg

African Journals Online (AJOL)

user

about knowledge level of pregnant women on obstetric danger signs. The objective of this .... ple size formula for estimating a single population proportion with the ..... subjects mentioned vaginal bleeding as danger sign during pregnancy ...

[Dangerous states and mental health disorders: perceptions and reality].

Science.gov (United States)

Tassone-Monchicourt, C; Daumerie, N; Caria, A; Benradia, I; Roelandt, J-L

2010-01-01

Image of Madness was always strongly linked with the notion of "dangerousness", provoking fear and social exclusion, despite the evolution of psychiatric practices and organisation, and the emphasis on user's rights respect. Mediatization and politicization of this issue through news item combining crime and mental illness, reinforce and spread out this perception. This paper presents a review of the litterature on social perceptions associating "dangerousness", "Insanity" and "mental illness", available data about the link between "dangerous states" and "psychiatric disorders", as well as the notion of "dangerousness" and the assessment of "dangerous state" of people suffering or not from psychiatric disorders. MAPPING OF SOCIAL REPRESENTATIONS: The French Survey "Mental Health in General Population: Images and Realities (MHGP)" was carried out between 1999 and 2003, on a representative sample of 36.000 individuals over 18 years old. It aims at describing the social representations of the population about "insanity/insane" and "mental illness/mentally ill". The results show that about 75% of the people interviewed link "insanity" or "mental illness" with "criminal or violent acts". Young people and those with a high level of education more frequently categorize violent and dangerous behaviours in the field of Mental illness rather than in that of madness. CORRELATION BETWEEN DANGEROUS STATE AND PSYCHIATRIC DISORDERS: in the scientific literature, all experts reject the hypothesis of a direct link between violence and mental disorder. Besides, 2 tendencies appear in their conclusions: on one hand, some studies establish a significative link between violence and severe mental illness, compared with the general population. On the other hand, results show that 87 to 97% of des aggressors are not mentally ills. Therefore, the absence of scientific consensus feeds the confusion and reinforce the link of causality between psychiatric disorders and violence. OFFICIAL

Defective chemokine signal integration in leukocytes lacking activator of G protein signaling 3 (AGS3).

Science.gov (United States)

Branham-O'Connor, Melissa; Robichaux, William G; Zhang, Xian-Kui; Cho, Hyeseon; Kehrl, John H; Lanier, Stephen M; Blumer, Joe B

2014-04-11

Activator of G-protein signaling 3 (AGS3, gene name G-protein signaling modulator-1, Gpsm1), an accessory protein for G-protein signaling, has functional roles in the kidney and CNS. Here we show that AGS3 is expressed in spleen, thymus, and bone marrow-derived dendritic cells, and is up-regulated upon leukocyte activation. We explored the role of AGS3 in immune cell function by characterizing chemokine receptor signaling in leukocytes from mice lacking AGS3. No obvious differences in lymphocyte subsets were observed. Interestingly, however, AGS3-null B and T lymphocytes and bone marrow-derived dendritic cells exhibited significant chemotactic defects as well as reductions in chemokine-stimulated calcium mobilization and altered ERK and Akt activation. These studies indicate a role for AGS3 in the regulation of G-protein signaling in the immune system, providing unexpected venues for the potential development of therapeutic agents that modulate immune function by targeting these regulatory mechanisms.

FEATURES FOR TRANSPORT AND AIR MECHANICAL SYSTEMS OF DANGEROUS GOODS

Directory of Open Access Journals (Sweden)

Eugen Dumitru BUSA

2012-05-01

Full Text Available Transport of dangerous goods are regulated activities, they take place under the direction and control of the authorities and specialized bodies in an institutional framework determined by national and international law. Of economic, transport infrastructure is the crucial element without which both production and trade would become meaningless, it is an essential element of a civilization, is also a necessary accessory of other economic activities.

Evaluation of non radiation dangerous in multipurpose reactor GAS

International Nuclear Information System (INIS)

Suwarto, S.

1998-01-01

Evaluation of the potential non irradiation dangerous in RSG-GAS included of : the fire dangerous, the chemical hazard and gas dangerous have been performed to evaluate its potential on causing the accident and evaluate the performance of the equipment to protect the accident. Evaluate the performance of the equipment to protect to accident . Evaluate to the fire dangerous performed by identified the potential dangerous of fire at each rooms and evaluate the performance of each equipment included of dry powder fire extinguishing system, hydrant system, fire detectors and alarm system. Evaluation to the chemical hazard and gas dangerous performed by identified the number and it's the management of chemical hazard in the chemical storage and laboratory. The result of evaluation included of data of the fire dangerous potential class and the performance of its equipment in each room in RSG-GAS and the data of the number and the management system of the chemical hazard and gas in chemical storage and chemical laboratory. From this evaluation it is concluded that the equipment of fire system are available to protect against the accident and the chemical hazard and gas potential are relating small, and has been managed properly

La mesure du danger

CERN Document Server

Manceron, Vanessa; Revet, Sandrine

2014-01-01

La mesure du danger permet d’explorer des dangers de nature aussi diverse que la délinquance, la pollution, l’écueil maritime, la maladie ou l’attaque sorcellaire, l’extinction d’espèces animales ou végétales, voire de la Planète tout entière. Au croisement de la sociologie, de l’anthropologie et de l’histoire, les différents articles analysent les pratiques concrètes de mesure pour tenter de comprendre ce qui se produit au cours de l’opération d’évaluation du danger sans préjuger de la nature de celui-ci. L’anthropologie a contribué à la réflexion sur l’infortune en s’intéressant aux temporalités de l’après : maladies, catastrophes, pandémies, etc. et en cherchant à rendre compte de l’expérience des victimes, de leur vie ordinaire bouleversée, de la recomposition du quotidien. Elle s’intéresse aussi aux autres types de mesures, les savoirs incorporés, qui reposent sur l’odorat, la vue ou le toucher et ceux qui ressortent d’une épistémologie « non ...

The relationship of individual psychological and individual-typological characteristics in individuals with personality disorders, committed socially dangerous acts

Directory of Open Access Journals (Sweden)

Dubinsky A.A.

2017-01-01

Full Text Available The relationship between individual psychological and individually-typological characteristics of patients with personality disorders who committed socially dangerous acts were studied, taking into account the severity of the organic factor and the degree of their social dangerousness. 121 males were surveyed, 70 of them were diagnosed with "organic personality disorder" and 33 - personality disorder. The types of personality disorders were diagnosed. The individual variables, the ratio of processes of system activation of behavior and its inhibition, protective styles, especially coping behaviours that constitute aggression, styles of self-regulation were analyzed. It was revealed that low settings of the system activation behavior found in the group of persons with a high degree of social dangerousness, determines the formation of individual psychological treats related to the rigidity behavior, the instability of the motives, impulsivity, negative emotionality, disinhibition. During comparison of samples of individuals with medium and high degree of social dangerousness it has been discovered that self-centeredness, as a component of self-control, high levels of affective components of aggression – anger and immature defense mechanisms significantly distinguish individuals with a high degree of public danger.

Reducing Future International Chemical and Biological Dangers.

Energy Technology Data Exchange (ETDEWEB)

Haddal, Chad [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Bull, Diana L. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Hernandez, Patricia Marie [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Foley, John T. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

2017-12-01

The International Biological and Chemical Threat Reduction Program at Sandia National Laboratories is developing a 15 - year technology road map in support the United States Government efforts to reduce international chemical and biological dangers . In 2017, the program leadership chartered an analysis team to explore dangers in the future international chemical and biological landscape through engagements with national security experts within and beyond Sandia to gain a multidisciplinary perspective on the future . This report offers a hi gh level landscape of future chemical and biological dangers based upon analysis of those engagements and provides support for further technology road map development.

A dangerous mixture

Directory of Open Access Journals (Sweden)

Anna Piva

2014-03-01

Full Text Available A 59-year old woman was admitted for fatigue and arm paresthesias with Trousseau sign. Her medical history included thyroidectomy and hypercholesterolemia recently treated with simvastatin. Laboratory tests showed severe hypokalemia and hypocalcemia, severe increase in muscle enzymes, metabolic alkalosis; low plasma renin activity, increased thyroid-stimulating hormone, normal free thyroxine, increased parathyroid hormone, decreased vitamin D3; alterations in electrolyte urinary excretion, cortisol and aldosterone were excluded. Hypothesizing a statin-related myopathy, simvastatin was suspended; the patient reported use of laxatives containing licorice. Electrolytes normalized with intravenous supplementation. Among many biochemical alterations, none stands out as a major cause for muscular and electrolyte disorders. All co-factors are inter-connected, starting with statin-induced myopathy, worsened by hypothyroidism, secondary hyperaldosteronism and vitamin D deficiency, leading to hypocalcemia and hypokalemia, perpetrating muscular and electrolyte disorders. The importance of considering clinical conditions as a whole emerges with multiple co-factors involved. Another issue concerns herbal products and their potential dangerous effects.

Colored Contact Lens Dangers

Medline Plus

Full Text Available ... Ophthalmology/Strabismus Ocular Pathology/Oncology Oculoplastics/Orbit Refractive Management/Intervention Retina/Vitreous Uveitis Focus ... Halloween Hazard: The Hidden Dangers of Buying Decorative Contact Lenses Without ...

DANGERS AND SAFETY MEASURES IN A MOUNTAIN

Directory of Open Access Journals (Sweden)

Jovica Petković

2013-07-01

Full Text Available Mountaineering and everything that is connected with it is a sport with con¬tro¬lled risk. Mountaineers, alpinists, climbers, cavers and all the others who visit and sojourn in mountains are faced with many risks and dangers, which are caused by na¬ture and also by their own mistakes. The dangers in the mountains, like dangers in any other environment, are mainly predictable, so it is best to deal with them with good esti¬mation, knowledge and skill. One has to be aware of his surroundings – the moun¬tain, to respect it and to know what is dangerous and how much it is dangerous at any moment. The organization of the mountaineering expeditions and leadership per¬haps re¬present the highest level of security control. To develop skills for organizing and lead¬ing a group means to ensure the safety of the entire group – to work pre¬ven¬ti¬ve¬ly at the level of the entire group, not only at the level of an individual. The success of the enti¬re group as well as safety depends on the organization and leadership.

Transport and handling of dangerous goods. Training of persons in charge of vehicles or vessels carrying dangerous goods by road or by inland waterways (Dangerous Goods 1979 No.1)

International Nuclear Information System (INIS)

1979-01-01

This Order supplements the Regulations of 15 April 1945 on the transport of dangerous goods by rail, land and inland waterways. It deals with the training of persons in charge of vehicles or boats carrying dangerous goods by road or by inland waterways. It refers in particular to transport of radioactive materials. (NEA) [fr

Are low radiation doses Dangerous?

International Nuclear Information System (INIS)

Garcia Lima, O.; Cornejo, N.

1996-01-01

In the last few years the answers to this questions has been affirmative as well as negative from a radiation protection point of view low doses of ionizing radiation potentially constitute an agent causing stochasting effects. A lineal relation without threshold is assumed between dose and probability of occurrence of these effects . Arguments against the danger of probability of occurrence of these effects. Arguments again the danger of low dose radiation are reflected in concepts such as Hormesis and adaptive response, which are phenomena that being studied at present

Dangerous Raw Oysters

Centers for Disease Control (CDC) Podcasts

2013-08-05

Dr. Duc Vugia, chief of the Infectious Diseases Branch at the California Department of Public Health, discusses the dangers of eating raw oysters.  Created: 8/5/2013 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 8/7/2013.

Ca2+ signaling in pancreatic acinar cells: physiology and pathophysiology

Directory of Open Access Journals (Sweden)

O.H. Petersen

2009-01-01

Full Text Available The pancreatic acinar cell is a classical model for studies of secretion and signal transduction mechanisms. Because of the extensive endoplasmic reticulum and the large granular compartment, it has been possible - by direct measurements - to obtain considerable insights into intracellular Ca2+ handling under both normal and pathological conditions. Recent studies have also revealed important characteristics of stimulus-secretion coupling mechanisms in isolated human pancreatic acinar cells. The acinar cells are potentially dangerous because of the high intra-granular concentration of proteases, which become inappropriately activated in the human disease acute pancreatitis. This disease is due to toxic Ca2+ signals generated by excessive liberation of Ca2+ from both the endoplasmic reticulum and the secretory granules.

Ways out of danger. Wege aus der Gefahr

Energy Technology Data Exchange (ETDEWEB)

Eppler, E

1981-01-01

The volume divides into five sections: ways out of danger; pressure leading into danger; what might save us, and will it grow to become effective; tedious paths out of danger; companions out of danger. The author puts the question whether the true art of politics will be restored. He shows that by reducing politics to mere crisis management we shall not be enabled to overcome the serious problems of the eighties. He points out future possibilities by making clear the chances and misdevelopments of energy policy, of foreign, development and defence policy. The political experience of recent years, the new approach showing different needs and ways of life should be taken seriously as hopeful signs and ought to be reflected in politics again.

Dangerous Animals Capture and Maintain Attention in Humans

OpenAIRE

Jessica L. Yorzinski; Michael J. Penkunas; Michael L. Platt; Richard G. Coss

2014-01-01

Predation is a major source of natural selection on primates and may have shaped attentional processes that allow primates to rapidly detect dangerous animals. Because ancestral humans were subjected to predation, a process that continues at very low frequencies, we examined the visual processes by which men and women detect dangerous animals (snakes and lions). We recorded the eye movements of participants as they detected images of a dangerous animal (target) among arrays of nondangerous an...

DMPD: Signaling pathways activated by microorganisms. [Dynamic Macrophage Pathway CSML Database

Lifescience Database Archive (English)

Full Text Available 17303405 Signaling pathways activated by microorganisms. Takeuchi O, Akira S. Curr ...Opin Cell Biol. 2007 Apr;19(2):185-91. Epub 2007 Feb 15. (.png) (.svg) (.html) (.csml) Show Signaling pathways activated by microorg...anisms. PubmedID 17303405 Title Signaling pathways activated by microorganisms. Auth

Electroporated Antigen-Encoding mRNA Is Not a Danger Signal to Human Mature Monocyte-Derived Dendritic Cells

Directory of Open Access Journals (Sweden)

Stefanie Hoyer

2015-01-01

Full Text Available For therapeutic cancer vaccination, the adoptive transfer of mRNA-electroporated dendritic cells (DCs is frequently performed, usually with monocyte-derived, cytokine-matured DCs (moDCs. However, DCs are rich in danger-sensing receptors which could recognize the exogenously delivered mRNA and induce DC activation, hence influencing the DCs’ immunogenicity. Therefore, we examined whether electroporation of mRNA with a proper cap and a poly-A tail of at least 64 adenosines had any influence on cocktail-matured moDCs. We used 16 different RNAs, encoding tumor antigens (MelanA, NRAS, BRAF, GNAQ, GNA11, and WT1, and variants thereof. None of those RNAs induced changes in the expression of CD25, CD40, CD83, CD86, and CD70 or the secretion of the cytokines IL-8, IL-6, and TNFα of more than 1.5-fold compared to the control condition, while an mRNA encoding an NF-κB-activation protein as positive control induced massive secretion of the cytokines. To determine whether mRNA electroporation had any effect on the whole transcriptome of the DCs, we performed microarray analyses of DCs of 6 different donors. None of 60,000 probes was significantly different between mock-electroporated DCs and MelanA-transfected DCs. Hence, we conclude that no transcriptional programs were induced within cocktail-matured DCs by electroporation of single tumor-antigen-encoding mRNAs.

Calcium-Oxidant Signaling Network Regulates AMP-activated Protein Kinase (AMPK) Activation upon Matrix Deprivation*

Science.gov (United States)

Sundararaman, Ananthalakshmy; Amirtham, Usha; Rangarajan, Annapoorni

2016-01-01

The AMP-activated protein kinase (AMPK) has recently been implicated in anoikis resistance. However, the molecular mechanisms that activate AMPK upon matrix detachment remain unexplored. In this study, we show that AMPK activation is a rapid and sustained phenomenon upon matrix deprivation, whereas re-attachment to the matrix leads to its dephosphorylation and inactivation. Because matrix detachment leads to loss of integrin signaling, we investigated whether integrin signaling negatively regulates AMPK activation. However, modulation of focal adhesion kinase or Src, the major downstream components of integrin signaling, failed to cause a corresponding change in AMPK signaling. Further investigations revealed that the upstream AMPK kinases liver kinase B1 (LKB1) and Ca2+/calmodulin-dependent protein kinase kinase β (CaMKKβ) contribute to AMPK activation upon detachment. In LKB1-deficient cells, we found AMPK activation to be predominantly dependent on CaMKKβ. We observed no change in ATP levels under detached conditions at early time points suggesting that rapid AMPK activation upon detachment was not triggered by energy stress. We demonstrate that matrix deprivation leads to a spike in intracellular calcium as well as oxidant signaling, and both these intracellular messengers contribute to rapid AMPK activation upon detachment. We further show that endoplasmic reticulum calcium release-induced store-operated calcium entry contributes to intracellular calcium increase, leading to reactive oxygen species production, and AMPK activation. We additionally show that the LKB1/CaMKK-AMPK axis and intracellular calcium levels play a critical role in anchorage-independent cancer sphere formation. Thus, the Ca2+/reactive oxygen species-triggered LKB1/CaMKK-AMPK signaling cascade may provide a quick, adaptable switch to promote survival of metastasizing cancer cells. PMID:27226623

NK cell activation: distinct stimulatory pathways counterbalancing inhibitory signals.

Science.gov (United States)

Bakker, A B; Wu, J; Phillips, J H; Lanier, L L

2000-01-01

A delicate balance between positive and negative signals regulates NK cell effector function. Activation of NK cells may be initiated by the triggering of multiple adhesion or costimulatory molecules, and can be counterbalanced by inhibitory signals induced by receptors for MHC class I. A common pathway of inhibitory signaling is provided by immunoreceptor tyrosine-based inhibitory motifs (ITIMs) in the cytoplasmic domains of these receptors which mediate the recruitment of SH2 domain-bearing tyrosine phosphate-1 (SHP-1). In contrast to the extensive progress that has been made regarding the negative regulation of NK cell function, our knowledge of the signals that activate NK cells is still poor. Recent studies of the activating receptor complexes have shed new light on the induction of NK cell effector function. Several NK receptors using novel adaptors with immunoreceptor tyrosine-based activation motifs (ITAMs) and with PI 3-kinase recruiting motifs have been implicated in NK cell stimulation.

Common activation of canonical Wnt signaling in pancreatic adenocarcinoma.

Directory of Open Access Journals (Sweden)

Marina Pasca di Magliano

2007-11-01

Full Text Available Pancreatic ductal adenocarcinoma (PDA is an extremely aggressive malignancy, which carries a dismal prognosis. Activating mutations of the Kras gene are common to the vast majority of human PDA. In addition, recent studies have demonstrated that embryonic signaling pathway such as Hedgehog and Notch are inappropriately upregulated in this disease. The role of another embryonic signaling pathway, namely the canonical Wnt cascade, is still controversial. Here, we use gene array analysis as a platform to demonstrate general activation of the canonical arm of the Wnt pathway in human PDA. Furthermore, we provide evidence for Wnt activation in mouse models of pancreatic cancer. Our results also indicate that Wnt signaling might be activated downstream of Hedgehog signaling, which is an early event in PDA evolution. Wnt inhibition blocked proliferation and induced apoptosis of cultured adenocarcinoma cells, thereby providing evidence to support the development of novel therapeutical strategies for Wnt inhibition in pancreatic adenocarcinoma.

The Danger of Contempt in Universities and in Modern Society

Science.gov (United States)

Sternberg, Robert J.

2017-01-01

Segments of modern U.S. society are rewarding rather than punishing the expression of contempt. College campuses are increasingly becoming tolerant of expressions of contempt rather than of respect for diversity of opinions. Universities need to take an active role in teaching students the danger of contempt because of its role in the development…

Robust Indoor Human Activity Recognition Using Wireless Signals.

Science.gov (United States)

Wang, Yi; Jiang, Xinli; Cao, Rongyu; Wang, Xiyang

2015-07-15

Wireless signals-based activity detection and recognition technology may be complementary to the existing vision-based methods, especially under the circumstance of occlusions, viewpoint change, complex background, lighting condition change, and so on. This paper explores the properties of the channel state information (CSI) of Wi-Fi signals, and presents a robust indoor daily human activity recognition framework with only one pair of transmission points (TP) and access points (AP). First of all, some indoor human actions are selected as primitive actions forming a training set. Then, an online filtering method is designed to make actions' CSI curves smooth and allow them to contain enough pattern information. Each primitive action pattern can be segmented from the outliers of its multi-input multi-output (MIMO) signals by a proposed segmentation method. Lastly, in online activities recognition, by selecting proper features and Support Vector Machine (SVM) based multi-classification, activities constituted by primitive actions can be recognized insensitive to the locations, orientations, and speeds.

Carbon dioxide dangers demonstration model

Science.gov (United States)

Venezky, Dina; Wessells, Stephen

2010-01-01

Carbon dioxide is a dangerous volcanic gas. When carbon dioxide seeps from the ground, it normally mixes with the air and dissipates rapidly. However, because carbon dioxide gas is heavier than air, it can collect in snowbanks, depressions, and poorly ventilated enclosures posing a potential danger to people and other living things. In this experiment we show how carbon dioxide gas displaces oxygen as it collects in low-lying areas. When carbon dioxide, created by mixing vinegar and baking soda, is added to a bowl with candles of different heights, the flames are extinguished as if by magic.

Alcohol Overdose: The Dangers of Drinking Too Much

Science.gov (United States)

... The Dangers of Drinking Too Much Print version Alcohol Overdose: The Dangers of Drinking Too Much Celebrating ... excess. And the results can be deadly. Identifying Alcohol Poisoning Critical Signs and Symptoms of Alcohol Poisoning ...

The Dangers of Educated Girls and Women

Science.gov (United States)

John, Vaughn M.

2016-01-01

Why do educated girls and women constitute a danger in some societies and for this face extreme danger in their educational endeavours? This article argues that historical and contemporary educational discrimination of girls and women is the hallmark of a violently patriarchal society, and this stubborn injustice is exacerbated under conditions of…

Colored Contact Lens Dangers

Science.gov (United States)

... Hazard: The Hidden Dangers of Buying Decorative Contact Lenses Without a Prescription Leer en Español: Peligros asociados ... truth." Real People, Real Problems with Colored Contact Lenses Julian: Teenager Blinded In One Eye By Non- ...

Neuroscience in forensic psychiatry: From responsibility to dangerousness. Ethical and legal implications of using neuroscience for dangerousness assessments.

Science.gov (United States)

Gkotsi, Georgia Martha; Gasser, Jacques

2016-01-01

Neuroscientific evidence is increasingly being used in criminal trials as part of psychiatric testimony. Up to now, "neurolaw" literature remained focused on the use of neuroscience for assessments of criminal responsibility. However, in the field of forensic psychiatry, responsibility assessments are progressively being weakened, whereas dangerousness and risk assessment gain increasing importance. In this paper, we argue that the introduction of neuroscientific data by forensic experts in criminal trials will be mostly be used in the future as a means to evaluate or as an indication of an offender's dangerousness, rather than their responsibility. Judges confronted with the pressure to ensure public security may tend to interpret neuroscientific knowledge and data as an objective and reliable way of evaluating one's risk of reoffending. First, we aim to show how the current socio-legal context has reshaped the task of the forensic psychiatrist, with dangerousness assessments prevailing. In the second part, we examine from a critical point of view the promise of neuroscience to serve a better criminal justice system by offering new tools for risk assessment. Then we aim to explain why neuroscientific evidence is likely to be used as evidence of dangerousness of the defendants. On a theoretical level, the current tendency in criminal policies to focus on prognostics of dangerousness seems to be "justified" by a utilitarian approach to punishment, supposedly revealed by new neuroscientific discoveries that challenge the notions of free will and responsibility. Although often promoted as progressive and humane, we believe that this approach could lead to an instrumentalization of neuroscience in the interest of public safety and give rise to interventions which could entail ethical caveats and run counter to the interests of the offenders. The last part of this paper deals with some of these issues-the danger of stigmatization for brain damaged offenders because of

Public Danger of Ecological Crime: Criminological Aspect​

Directory of Open Access Journals (Sweden)

Kuznetsova Natalya I.

2018-03-01

Full Text Available This article describes the characteristics of public danger of ecological crime. Specific features that distinguish it from other types of criminality are analyzed. Identified and justified are such features of environmental crime as an increased level of public danger, a wider range of victims, the continuing and deferred nature of the negative consequences, their transboundary nature, the irreversibility of the consequences, causing significant harm to the economic interests of the state, expressed in the withdrawal from the legal turnover of huge amounts of valuable natural resources. On the basis of the conducted research the author suggests wide use of the integrated criminological approach to studying the public danger of environmental crime taking into account its quantitative and qualitative characteristics.

Modulation of β-catenin signaling by glucagon receptor activation.

Directory of Open Access Journals (Sweden)

Jiyuan Ke

Full Text Available The glucagon receptor (GCGR is a member of the class B G protein-coupled receptor family. Activation of GCGR by glucagon leads to increased glucose production by the liver. Thus, glucagon is a key component of glucose homeostasis by counteracting the effect of insulin. In this report, we found that in addition to activation of the classic cAMP/protein kinase A (PKA pathway, activation of GCGR also induced β-catenin stabilization and activated β-catenin-mediated transcription. Activation of β-catenin signaling was PKA-dependent, consistent with previous reports on the parathyroid hormone receptor type 1 (PTH1R and glucagon-like peptide 1 (GLP-1R receptors. Since low-density-lipoprotein receptor-related protein 5 (Lrp5 is an essential co-receptor required for Wnt protein mediated β-catenin signaling, we examined the role of Lrp5 in glucagon-induced β-catenin signaling. Cotransfection with Lrp5 enhanced the glucagon-induced β-catenin stabilization and TCF promoter-mediated transcription. Inhibiting Lrp5/6 function using Dickkopf-1(DKK1 or by expression of the Lrp5 extracellular domain blocked glucagon-induced β-catenin signaling. Furthermore, we showed that Lrp5 physically interacted with GCGR by immunoprecipitation and bioluminescence resonance energy transfer assays. Together, these results reveal an unexpected crosstalk between glucagon and β-catenin signaling, and may help to explain the metabolic phenotypes of Lrp5/6 mutations.

Colored Contact Lens Dangers

Medline Plus

Full Text Available ... Hazard: The Hidden Dangers of Buying Decorative Contact Lenses Without a Prescription Leer en Español: Peligros asociados ... truth." Real People, Real Problems with Colored Contact Lenses Julian: Teenager Blinded In One Eye By Non- ...

Colored Contact Lens Dangers

Medline Plus

Full Text Available ... Español Eye Health / News Halloween Hazard: The Hidden Dangers of Buying Decorative Contact Lenses Without a Prescription ... be purchased over-the-counter or on the Internet," says Thomas Steinemann, MD, professor of ophthalmology at ...

Activation of the Extracellular Signal-Regulated Kinase Signaling Is Critical for Human Umbilical Cord Mesenchymal Stem Cell Osteogenic Differentiation

Directory of Open Access Journals (Sweden)

Chen-Shuang Li

2016-01-01

Full Text Available Human umbilical cord mesenchymal stem cells (hUCMSCs are recognized as candidate progenitor cells for bone regeneration. However, the mechanism of hUCMSC osteogenesis remains unclear. In this study, we revealed that mitogen-activated protein kinases (MAPKs signaling is involved in hUCMSC osteogenic differentiation in vitro. Particularly, the activation of c-Jun N-terminal kinases (JNK and p38 signaling pathways maintained a consistent level in hUCMSCs through the entire 21-day osteogenic differentiation period. At the same time, the activation of extracellular signal-regulated kinases (ERK signaling significantly increased from day 5, peaked at day 9, and declined thereafter. Moreover, gene profiling of osteogenic markers, alkaline phosphatase (ALP activity measurement, and alizarin red staining demonstrated that the application of U0126, a specific inhibitor for ERK activation, completely prohibited hUCMSC osteogenic differentiation. However, when U0126 was removed from the culture at day 9, ERK activation and osteogenic differentiation of hUCMSCs were partially recovered. Together, these findings demonstrate that the activation of ERK signaling is essential for hUCMSC osteogenic differentiation, which points out the significance of ERK signaling pathway to regulate the osteogenic differentiation of hUCMSCs as an alternative cell source for bone tissue engineering.

Colored Contact Lens Dangers

Medline Plus

Full Text Available ... Tips & Prevention News Ask an Ophthalmologist Patient Stories Español Eye Health / News Halloween Hazard: The Hidden Dangers ... Decorative Contact Lenses Without a Prescription Leer en Español: Peligros asociados con los lentes de contacto de ...

The merchant shipping (dangerous goods) (amendment) rules 1980 No. 789

International Nuclear Information System (INIS)

1980-01-01

These Rules amend the Merchant Shipping Rules 1978 and revoke the Merchant Shipping (Dangerous Goods) (Amendment) Rules 1979. The purpose of this amendment is to update the references to the 1978 Report of the Department of Trade's Standing Advisory Committee on the Carriage of Dangerous Goods in Ships (the Blue Book) and the 1977 Edition of the International Maritime Dangerous Goods Code of IMCO (the IMDG Code), referred to in the 1978 Rules. The amendments concern, inter alia, marking of packages on board ship which contain dangerous goods, including radioactive materials (NEA) [fr

The application of dangerous goods regulations to the transport of radioactive wastes

International Nuclear Information System (INIS)

Blenkin, J.J.; Darby, W.P.; Heywood, J.D.; Wikinson, H.L.; Carrington, C.K.; Murray, M.A.

1998-01-01

Some radioactive materials to be transported, including certain radioactive wastes, contain materials that qualify as dangerous goods as defined by the United Nations Recommendations on the Transport of Dangerous Goods (United Nations 1997). The regulations governing the transport of radioactive and dangerous goods in the UK are largely based on the IAEA Regulations for the Safe Transport of Radioactive Material (IAEA 1990) and the UN Recommendations (United Nations 1993). Additional legislation will also apply including the Carriage of Dangerous Goods by Road (Driver Training) Regulations 1996 (UK 1996). The IAEA Transport Regulations are clear that where radioactive materials have other dangerous properties the requirements of other relevant transport regulations for dangerous goods must also be met. They require that consignments are appropriately segregated from other dangerous goods, in accordance with relevant legislation, and that dangerous properties such as explosiveness, flammability etc. are taken into account in packing, labelling, marking, placarding, storage and transport. In practice, however, it requires a clear understanding of the relationship between the IAEA Transport Regulations and other dangerous goods legislation in order to avoid a number of problems in the approval of package design. This paper discusses the regulations applying to the transport of dangerous goods and explores practical problems associated with implementing them. It highlights a number of opportunities for developing the regulations, to make them easier to apply to radioactive materials that also have other potentially dangerous properties. (authors)

The Growth Hormone Receptor: Mechanism of Receptor Activation, Cell Signaling, and Physiological Aspects

Directory of Open Access Journals (Sweden)

Farhad Dehkhoda

2018-02-01

Full Text Available The growth hormone receptor (GHR, although most well known for regulating growth, has many other important biological functions including regulating metabolism and controlling physiological processes related to the hepatobiliary, cardiovascular, renal, gastrointestinal, and reproductive systems. In addition, growth hormone signaling is an important regulator of aging and plays a significant role in cancer development. Growth hormone activates the Janus kinase (JAK–signal transducer and activator of transcription (STAT signaling pathway, and recent studies have provided a new understanding of the mechanism of JAK2 activation by growth hormone binding to its receptor. JAK2 activation is required for growth hormone-mediated activation of STAT1, STAT3, and STAT5, and the negative regulation of JAK–STAT signaling comprises an important step in the control of this signaling pathway. The GHR also activates the Src family kinase signaling pathway independent of JAK2. This review covers the molecular mechanisms of GHR activation and signal transduction as well as the physiological consequences of growth hormone signaling.

Chemical signal activation of an organocatalyst enables control over soft material formation.

Science.gov (United States)

Trausel, Fanny; Maity, Chandan; Poolman, Jos M; Kouwenberg, D S J; Versluis, Frank; van Esch, Jan H; Eelkema, Rienk

2017-10-12

Cells can react to their environment by changing the activity of enzymes in response to specific chemical signals. Artificial catalysts capable of being activated by chemical signals are rare, but of interest for creating autonomously responsive materials. We present an organocatalyst that is activated by a chemical signal, enabling temporal control over reaction rates and the formation of materials. Using self-immolative chemistry, we design a deactivated aniline organocatalyst that is activated by the chemical signal hydrogen peroxide and catalyses hydrazone formation. Upon activation of the catalyst, the rate of hydrazone formation increases 10-fold almost instantly. The responsive organocatalyst enables temporal control over the formation of gels featuring hydrazone bonds. The generic design should enable the use of a large range of triggers and organocatalysts, and appears a promising method for the introduction of signal response in materials, constituting a first step towards achieving communication between artificial chemical systems.Enzymes regulated by chemical signals are common in biology, but few such artificial catalysts exist. Here, the authors design an aniline catalyst that, when activated by a chemical trigger, catalyses formation of hydrazone-based gels, demonstrating signal response in a soft material.

Hostility, driving anger, and dangerous driving: the emerging role of hemispheric preference.

Science.gov (United States)

Gidron, Yori; Gaygısız, Esma; Lajunen, Timo

2014-12-01

Various studies have implicated psychosocial variables (e.g., hostility) in risk of dangerous driving and traffic accidents. However, whether these variables are related to more basic neurobiological factors, and whether such associations have implications for the modification of psychosocial risk factors in the context of driving, have not been examined in depth. This study examined the relationship between hemispheric preference (HP), hostility and self-reported dangerous driving, and the ability to affect driving anger via hemisphere activating cognitive exercises (HACE). In Study 1, 254 Turkish students completed questionnaires of hostility, HP and driving behavior. In Study 2, we conducted a "proof of concept" experimental study, and tested effects of left, right and neutral HACE on driving anger, by exposing N=650 Turkish students to written scenarios including either logical (left hemisphere), visuo-spatial (right hemisphere) or "mild doses" of both types of contents (control). In Study 1, left-HP was associated with higher hostility and with more dangerous driving, and hostility mediated the relationship between L-HP and reported driving behavior. In Study 2, only right-HACE led to immediate significant reductions in self-reported driving anger. Left-HP is related to hostility and to dangerous driving, and it may be possible to partly reduce driving anger by right-HACE. Future studies must replicate these findings with objective measures, more enduring interventions and longer follow-ups. Copyright © 2014. Published by Elsevier Ltd.

The Merchant Shipping (Dangerous Goods) Rules 1978 (Statutory Instrument 1543, 25 October 1978)

International Nuclear Information System (INIS)

1978-01-01

These Rules supersede the Merchant Shipping (Dangerous Goods) Rule of 1965 as amended by the Merchant Shipping (Dangerous Goods) (Amendment) Rules of 1968 and 1972. The Rules now define 'dangerous goods' by reference to goods classified as dangerous for carriage by sea as well as any other goods whose properties might be dangerous it they were carried by sea. This classification is based on that of the 1978 Report of the Standing Advisory Committee on the Carriage of Dangerous Goods of the Department of Trade, and the 1977 Edition of the International Maritime Dangerous Goods Code published by the Intergovernmental Maritime consultative Organisation. (NEA) [fr

Rural Tanzanian women's awareness of danger signs of obstetric complications

Directory of Open Access Journals (Sweden)

Lindmark Gunilla

2009-03-01

Full Text Available Abstract Background Awareness of the danger signs of obstetric complications is the essential first step in accepting appropriate and timely referral to obstetric and newborn care. The objectives of this study were to assess women's awareness of danger signs of obstetric complications and to identify associated factors in a rural district in Tanzania. Methods A total of 1118 women who had been pregnant in the past two years were interviewed. A list of medically recognized potentially life threatening obstetric signs was obtained from the responses given. Chi- square test was used to determine associations between categorical variables and multivariate logistic regression analysis was used to identify factors associated with awareness of obstetric danger signs. Results More than 98% of the women attended antenatal care at least once. Half of the women knew at least one obstetric danger sign. The percentage of women who knew at least one danger sign during pregnancy was 26%, during delivery 23% and after delivery 40%. Few women knew three or more danger signs. According to multivariate logistic regression analysis having secondary education or more increased the likelihood of awareness of obstetric danger signs six-fold (OR = 5.8; 95% CI: 1.8–19 in comparison with no education at all. The likelihood to have more awareness increased significantly by increasing age of the mother, number of deliveries, number of antenatal visits, whether the delivery took place at a health institution and whether the mother was informed of having a risks/complications during antenatal care. Conclusion Women had low awareness of danger signs of obstetric complications. We recommend the following in order to increase awareness of danger signs of obstetrical complications: to improve quality of counseling and involving other family members in antenatal and postnatal care, to use radio messages and educational sessions targeting the whole community and to intensify

Colored Contact Lens Dangers

Medline Plus

Full Text Available ... Health / News Halloween Hazard: The Hidden Dangers of Buying Decorative Contact Lenses Without a Prescription Leer en Español: Peligros asociados con los lentes de contacto de color Sep. 26, 2013 It started as an impulsive buy from a souvenir shop, but 10 hours ...

Structural basis of arrestin-3 activation and signaling

Energy Technology Data Exchange (ETDEWEB)

Chen, Qiuyan; Perry, Nicole A.; Vishnivetskiy, Sergey A.; Berndt, Sandra; Gilbert, Nathaniel C.; Zhuo, Ya; Singh, Prashant K.; Tholen, Jonas; Ohi, Melanie D.; Gurevich, Eugenia V.; Brautigam, Chad A.; Klug, Candice S.; Gurevich, Vsevolod V.; Iverson, T.M. (UTSMC); (MCW); (Vanderbilt); (UASANS)

2017-11-10

A unique aspect of arrestin-3 is its ability to support both receptor-dependent and receptor-independent signaling. Here, we show that inositol hexakisphosphate (IP6) is a non-receptor activator of arrestin-3 and report the structure of IP6-activated arrestin-3 at 2.4-Å resolution. IP6-activated arrestin-3 exhibits an inter-domain twist and a displaced C-tail, hallmarks of active arrestin. IP6 binds to the arrestin phosphate sensor, and is stabilized by trimerization. Analysis of the trimerization surface, which is also the receptor-binding surface, suggests a feature called the finger loop as a key region of the activation sensor. We show that finger loop helicity and flexibility may underlie coupling to hundreds of diverse receptors and also promote arrestin-3 activation by IP6. Importantly, we show that effector-binding sites on arrestins have distinct conformations in the basal and activated states, acting as switch regions. These switch regions may work with the inter-domain twist to initiate and direct arrestin-mediated signaling.

Mitogen activated protein kinase signaling in the kidney: Target for intervention?

NARCIS (Netherlands)

de Borst, M.H.; Wassef, L.; Kelly, D.J.; van Goor, H.; Navis, Ger Jan

2006-01-01

Mitogen activated protein kinases (MAPKs) are intracellular signal transduction molecules, which connect cell-surface receptor signals to intracellular processes. MAPKs regulate a range of cellular activities including cell proliferation, gene expression, apoptosis, cell differentiation and cytokine

Using crowd sourcing to combat potentially illegal or dangerous UAV operations

Science.gov (United States)

Tapsall, Brooke T.

2016-10-01

The UAV (Unmanned Aerial Vehicles) industry is growing exponentially at a pace that policy makers, individual countries and law enforcement agencies are finding difficult to keep up. The UAV market is large, as such the amount of UAVs being operated in potentially dangerous situations is prevalent and rapidly increasing. Media is continually reporting `near-miss' incidents between UAVs and commercial aircraft, UAV breaching security in sensitive areas or invading public privacy. One major challenge for law enforcement agencies is gaining tangible evidence against potentially dangerous or illegal UAV operators due to the rapidity with which UAV operators are able to enter, fly and exit a scene before authorities can arrive or before they can be located. DroneALERT, an application available via the Airport-UAV.com website, allows users to capture potentially dangerous or illegal UAV activity using their mobile device as it the incident is occurring. A short online DroneALERT Incident Report (DIR) is produced, emailed to the user and the Airport-UAV.com custodians. The DIR can be used to aid authorities in their investigations. The DIR contains details such as images and videos, location, time, date of the incident, drone model, its distance and height. By analysing information from the DIR, photos or video, there is a high potential for law enforcement authorities to use this evidence to identify the type of UAV used, triangulate the location of the potential dangerous UAV and operator, create a timeline of events, potential areas of operator exit and to determine the legalities breached. All provides crucial evidence for identifying and prosecuting a UAV operator.

Grout treatment facility dangerous waste permit application

International Nuclear Information System (INIS)

1988-01-01

This section briefly describes the Hanford Site, provides a general description of the site operations and administration, provides an overview of the contents of this Grout Treatment Facility (GTF) Permit Application, and gives a list of acronyms and abbreviations used in the document. The decision was made to use the checklist as a locator reference instead of using the checklist section numbers as paragraph section numbers because several different types of waste management units, some of which are not addressed in the checklists, are part of the GTF. The GTF is a waste management unit within the Hanford Site facility. In May 1988, permit application was filed that identified the GTF as an existing facility. The GTF mixes dry cementitious solids with liquid mixed wastes (containing both dangerous and radioactive constituents) produced by Hanford Site operations. In addition to the design and operating features of the GTF that are intended to meet the requirements of dangerous waste regulations, many additional design and operating features are necessary to comply with radioactive waste management practices. The GTF design features and practices are intended to keep operational exposure to radionuclides and dangerous substances ''as low as reasonably achievable'' (ALARA) and to provide a disposal system that protects the environment for at least 10,000 yr. In some instances, ALARA practices present difficulties when complying with requirements of dangerous waste regulations

Recent insights into the molecular mechanisms of the NLRP3 inflammasome activation [version 1; referees: 2 approved

Directory of Open Access Journals (Sweden)

Tomasz Próchnicki

2016-06-01

Full Text Available Inflammasomes are high-molecular-weight protein complexes that are formed in the cytosolic compartment in response to danger- or pathogen-associated molecular patterns. These complexes enable activation of an inflammatory protease caspase-1, leading to a cell death process called pyroptosis and to proteolytic cleavage and release of pro-inflammatory cytokines interleukin (IL-1β and IL-18. Along with caspase-1, inflammasome components include an adaptor protein, ASC, and a sensor protein, which triggers the inflammasome assembly in response to a danger signal. The inflammasome sensor proteins are pattern recognition receptors belonging either to the NOD-like receptor (NLR or to the AIM2-like receptor family. While the molecular agonists that induce inflammasome formation by AIM2 and by several other NLRs have been identified, it is not well understood how the NLR family member NLRP3 is activated. Given that NLRP3 activation is relevant to a range of human pathological conditions, significant attempts are being made to elucidate the molecular mechanism of this process. In this review, we summarize the current knowledge on the molecular events that lead to activation of the NLRP3 inflammasome in response to a range of K+ efflux-inducing danger signals. We also comment on the reported involvement of cytosolic Ca2+ fluxes on NLRP3 activation. We outline the recent advances in research on the physiological and pharmacological mechanisms of regulation of NLRP3 responses, and we point to several open questions regarding the current model of NLRP3 activation.

Effect of direct and indirect contact with mental illness on dangerousness and social distance.

Science.gov (United States)

Lee, Minhwa; Seo, Mikyung

2018-03-01

This study is based on the contact hypothesis that contact with mental illness is the most effective anti-stigma strategy. This study aims to analyze which form of contact can most effectively decrease the dangerousness and social distance associated with schizophrenia, depression and alcoholism. In total, 573 Korean adults ( M age  = 43.71 years, standard deviation ( SD) = 13.41; 54.1% male, 45.9% female) were surveyed about randomly assigned vignettes of schizophrenia, depression and alcoholism. The participants were questioned on the dangerousness and social distance associated with the assigned vignette, as well as direct and indirect contact experience with the mental illness. Two-way analysis of variance (ANOVA) was used to determine the main effect and interaction effect that the type of mental illness and contact experience have on the two dependent variables (dangerousness and social distance). The findings show that the type of mental illness has a significant main effect on dangerousness and social distance, but contact type only has a significant main effect on social distance. Moreover, the two independent variables (mental illness subtype and contact experience) have an interaction effect on two dependent variables (dangerousness and social distance). Therefore, the anti-stigma effect of contact varies according to the type of mental illness. Our findings suggest that appropriate anti-stigma strategies are required for each type of mental illness. Considering that opportunities for direct contact with persons with mental illness are highly limited, it is necessary to actively utilize indirect contact.

In roots of Arabidopsis thaliana, the damage-associated molecular pattern AtPep1 is a stronger elicitor of immune signalling than flg22 or the chitin heptamer.

Directory of Open Access Journals (Sweden)

Lorenzo Poncini

Full Text Available Plants interpret their immediate environment through perception of small molecules. Microbe-associated molecular patterns (MAMPs such as flagellin and chitin are likely to be more abundant in the rhizosphere than plant-derived damage-associated molecular patterns (DAMPs. We investigated how the Arabidopsis thaliana root interprets MAMPs and DAMPs as danger signals. We monitored root development during exposure to increasing concentrations of the MAMPs flg22 and the chitin heptamer as well as of the DAMP AtPep1. The tissue-specific expression of defence-related genes in roots was analysed using a toolkit of promoter::YFPN lines reporting jasmonic acid (JA-, salicylic acid (SA-, ethylene (ET- and reactive oxygen species (ROS- dependent signalling. Finally, marker responses were analysed during invasion by the root pathogen Fusarium oxysporum. The DAMP AtPep1 triggered a stronger activation of the defence markers compared to flg22 and the chitin heptamer. In contrast to the tested MAMPs, AtPep1 induced SA- and JA-signalling markers in the root and caused a severe inhibition of root growth. Fungal attack resulted in a strong activation of defence genes in tissues close to the invading fungal hyphae. The results collectively suggest that AtPep1 presents a stronger danger signal to the Arabidopsis root than the MAMPs flg22 and chitin heptamer.

Intercellular signaling pathways active during intervertebral disc growth, differentiation, and aging.

Science.gov (United States)

Dahia, Chitra Lekha; Mahoney, Eric J; Durrani, Atiq A; Wylie, Christopher

2009-03-01

Intervertebral discs at different postnatal ages were assessed for active intercellular signaling pathways. To generate a spatial and temporal map of the signaling pathways active in the postnatal intervertebral disc (IVD). The postnatal IVD is a complex structure, consisting of 3 histologically distinct components, the nucleus pulposus, fibrous anulus fibrosus, and endplate. These differentiate and grow during the first 9 weeks of age in the mouse. Identification of the major signaling pathways active during and after the growth and differentiation period will allow functional analysis using mouse genetics and identify targets for therapy for individual components of the disc. Antibodies specific for individual cell signaling pathways were used on cryostat sections of IVD at different postnatal ages to identify which components of the IVD were responding to major classes of intercellular signal, including sonic hedgehog, Wnt, TGFbeta, FGF, and BMPs. We present a spatial/temporal map of these signaling pathways during growth, differentiation, and aging of the disc. During growth and differentiation of the disc, its different components respond at different times to different intercellular signaling ligands. Most of these are dramatically downregulated at the end of disc growth.

Hanford Facility Dangerous Waste Permit Application, 200 Area Effluent Treatment Facility

International Nuclear Information System (INIS)

1993-08-01

The 200 Area Effluent Treatment Facility Dangerous Waste Permit Application documentation consists of both Part A and a Part B permit application documentation. An explanation of the Part A revisions associated with this treatment and storage unit, including the current revision, is provided at the beginning of the Part A section. Once the initial Hanford Facility Dangerous Waste Permit is issued, the following process will be used. As final, certified treatment, storage, and/or disposal unit-specific documents are developed, and completeness notifications are made by the US Environmental Protection Agency and the Washington State Department of Ecology, additional unit-specific permit conditions will be incorporated into the Hanford Facility Dangerous Waste Permit through the permit modification process. All treatment, storage, and/or disposal units that are included in the Hanford Facility Dangerous Waste Permit Application will operate under interim status until final status conditions for these units are incorporated into the Hanford Facility Dangerous Waste Permit. The Hanford Facility Dangerous Waste Permit Application, 200 Area Effluent Treatment Facility contains information current as of May 1, 1993

Hanford Facility Dangerous Waste Permit Application, 200 Area Effluent Treatment Facility

Energy Technology Data Exchange (ETDEWEB)

1993-08-01

The 200 Area Effluent Treatment Facility Dangerous Waste Permit Application documentation consists of both Part A and a Part B permit application documentation. An explanation of the Part A revisions associated with this treatment and storage unit, including the current revision, is provided at the beginning of the Part A section. Once the initial Hanford Facility Dangerous Waste Permit is issued, the following process will be used. As final, certified treatment, storage, and/or disposal unit-specific documents are developed, and completeness notifications are made by the US Environmental Protection Agency and the Washington State Department of Ecology, additional unit-specific permit conditions will be incorporated into the Hanford Facility Dangerous Waste Permit through the permit modification process. All treatment, storage, and/or disposal units that are included in the Hanford Facility Dangerous Waste Permit Application will operate under interim status until final status conditions for these units are incorporated into the Hanford Facility Dangerous Waste Permit. The Hanford Facility Dangerous Waste Permit Application, 200 Area Effluent Treatment Facility contains information current as of May 1, 1993.

Heat Shock Proteins as Danger Signals for Cancer Detection

International Nuclear Information System (INIS)

Seigneuric, Renaud; Mjahed, Hajare; Gobbo, Jessica; Joly, Anne-Laure; Berthenet, Kevin; Shirley, Sarah; Garrido, Carmen

2011-01-01

First discovered in 1962, heat shock proteins (HSPs) are highly studied with about 35,500 publications on the subject to date. HSPs are highly conserved, function as molecular chaperones for a large panel of “client” proteins and have strong cytoprotective properties. Induced by many different stress signals, they promote cell survival in adverse conditions. Therefore, their roles have been investigated in several conditions and pathologies where HSPs accumulate, such as in cancer. Among the diverse mammalian HSPs, some members share several features that may qualify them as cancer biomarkers. This review focuses mainly on three inducible HSPs: HSP27, HPS70, and HSP90. Our survey of recent literature highlights some recurring weaknesses in studies of the HSPs, but also identifies findings that indicate that some HSPs have potential as cancer biomarkers for successful clinical applications.

ROS-related redox regulation and signaling in plants.

Science.gov (United States)

Noctor, Graham; Reichheld, Jean-Philippe; Foyer, Christine H

2017-07-18

As sessile oxygenic organisms with a plastic developmental programme, plants are uniquely positioned to exploit reactive oxygen species (ROS) as powerful signals. Plants harbor numerous ROS-generating pathways, and these oxidants and related redox-active compounds have become tightly embedded into plant function and development during the course of evolution. One dominant view of ROS-removing systems sees them as beneficial antioxidants battling to keep damaging ROS below dangerous levels. However, it is now established that ROS are a necessary part of subcellular and intercellular communication in plants and that some of their signaling functions require ROS-metabolizing systems. For these reasons, it is suggested that "ROS processing systems" would be a more accurate term than "antioxidative systems" to describe cellular components that are most likely to interact with ROS and, in doing so, transmit oxidative signals. Within this framework, our update provides an overview of the complexity and compartmentation of ROS production and removal. We place particular emphasis on the importance of ROS-interacting systems such as the complex cellular thiol network in the redox regulation of phytohormone signaling pathways that are crucial for plant development and defense against external threats. Copyright © 2017 Elsevier Ltd. All rights reserved.

Hedgehog signal activation coordinates proliferation and differentiation of fetal liver progenitor cells

International Nuclear Information System (INIS)

Hirose, Yoshikazu; Itoh, Tohru; Miyajima, Atsushi

2009-01-01

Hedgehog (Hh) signaling plays crucial roles in development and homeostasis of various organs. In the adult liver, it regulates proliferation and/or viability of several types of cells, particularly under injured conditions, and is also implicated in stem/progenitor cell maintenance. However, the role of this signaling pathway during the normal developmental process of the liver remains elusive. Although Sonic hedgehog (Shh) is expressed in the ventral foregut endoderm from which the liver derives, the expression disappears at the onset of the liver bud formation, and its possible recurrence at the later stages has not been investigated. Here we analyzed the activation and functional relevance of Hh signaling during the mouse fetal liver development. At E11.5, Shh and an activation marker gene for Hh signaling, Gli1, were expressed in Dlk + hepatoblasts, the fetal liver progenitor cells, and the expression was rapidly decreased thereafter as the development proceeded. In the culture of Dlk + hepatoblasts isolated from the E11.5 liver, activation of Hh signaling stimulated their proliferation and this effect was cancelled by a chemical Hh signaling inhibitor, cyclopamine. In contrast, hepatocyte differentiation of Dlk + hepatoblasts in vitro as manifested by the marker gene expression and acquisition of ammonia clearance activity was significantly inhibited by forced activation of Hh signaling. Taken together, these results demonstrate the temporally restricted manner of Hh signal activation and its role in promoting the hepatoblast proliferation, and further suggest that the pathway needs to be shut off for the subsequent hepatic differentiation of hepatoblasts to proceed normally.

Wise, a context-dependent activator and inhibitor of Wnt signalling.

Science.gov (United States)

Itasaki, Nobue; Jones, C Michael; Mercurio, Sara; Rowe, Alison; Domingos, Pedro M; Smith, James C; Krumlauf, Robb

2003-09-01

We have isolated a novel secreted molecule, Wise, by a functional screen for activities that alter the anteroposterior character of neuralised Xenopus animal caps. Wise encodes a secreted protein capable of inducing posterior neural markers at a distance. Phenotypes arising from ectopic expression or depletion of Wise resemble those obtained when Wnt signalling is altered. In animal cap assays, posterior neural markers can be induced by Wnt family members, and induction of these markers by Wise requires components of the canonical Wnt pathway. This indicates that in this context Wise activates the Wnt signalling cascade by mimicking some of the effects of Wnt ligands. Activation of the pathway was further confirmed by nuclear accumulation of beta-catenin driven by Wise. By contrast, in an assay for secondary axis induction, extracellularly Wise antagonises the axis-inducing ability of Wnt8. Thus, Wise can activate or inhibit Wnt signalling in a context-dependent manner. The Wise protein physically interacts with the Wnt co-receptor, lipoprotein receptor-related protein 6 (LRP6), and is able to compete with Wnt8 for binding to LRP6. These activities of Wise provide a new mechanism for integrating inputs through the Wnt coreceptor complex to modulate the balance of Wnt signalling.

The term of danger in the surveillance procedure under atomic energy law

International Nuclear Information System (INIS)

Roller, G.

1993-01-01

Article 19 Section 3 of the Atomic Energy Law is gaining more and more practical significance. This can be seen from the dispute about the reach of the term of danger under atomic energy law, among other issues. The article examines the prerequisites for an offence pursuant to Article 19 Section 3 of the Atomic Energy Law - danger, suspected danger, 'acute' danger - and then goes on to deal with the term of danger as concretized by sublegislative rulings - concept of predefined accidents as an interpretative aid, their significance in the context of taking precautions against damage, consequences of the uncontrollability of such accidents. The legal consequences of this include the authorities' discretion when and how to act, exept for cases of grave danger where this discretion is reduced 'to zero', i.e. the authority is compelled to act. (orig./HSCH) [de

Defense to Sclerotinia sclerotiorum in oilseed rape is associated with the sequential activations of salicylic acid signaling and jasmonic acid signaling.

Science.gov (United States)

Wang, Zheng; Tan, Xiaoli; Zhang, Zhiyan; Gu, Shoulai; Li, Guanying; Shi, Haifeng

2012-03-01

Signaling pathways mediated by salicylic acid (SA) and jasmonic acid (JA) are widely studied in various host-pathogen interactions. For oilseed rape (Brassica napus)-Sclerotinia sclerotiorum interaction, little information of the two signaling molecules has been described in detail. In this study, we showed that the level of SA and JA in B. napus leaves was increased with a distinct temporal profile, respectively, after S. sclerotiorum infection. The application of SA or methyl jasmonate enhanced the resistance to the pathogen. Furthermore, a set of SA and JA signaling marker genes were identified from B. napus and were used to monitor the signaling responses to S. sclerotiorum infection by examining the temporal expression profiles of these marker genes. The SA signaling was activated within 12h post inoculation (hpi) followed by the JA signaling which was activated around 24 hpi. In addition, SA-JA crosstalk genes were activated during this process. These results suggested that defense against S. sclerotiorum in oilseed rape is associated with a sequential activation of SA signaling and JA signaling, which provide important clues for designing strategies to curb diseases caused by S. sclerotioru. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Metabolic signals and innate immune activation in obesity and exercise.

Science.gov (United States)

Ringseis, Robert; Eder, Klaus; Mooren, Frank C; Krüger, Karsten

2015-01-01

The combination of a sedentary lifestyle and excess energy intake has led to an increased prevalence of obesity which constitutes a major risk factor for several co-morbidities including type 2 diabetes and cardiovascular diseases. Intensive research during the last two decades has revealed that a characteristic feature of obesity linking it to insulin resistance is the presence of chronic low-grade inflammation being indicative of activation of the innate immune system. Recent evidence suggests that activation of the innate immune system in the course of obesity is mediated by metabolic signals, such as free fatty acids (FFAs), being elevated in many obese subjects, through activation of pattern recognition receptors thereby leading to stimulation of critical inflammatory signaling cascades, like IκBα kinase/nuclear factor-κB (IKK/NF- κB), endoplasmic reticulum (ER) stress-induced unfolded protein response (UPR) and NOD-like receptor P3 (NLRP3) inflammasome pathway, that interfere with insulin signaling. Exercise is one of the main prescribed interventions in obesity management improving insulin sensitivity and reducing obesity- induced chronic inflammation. This review summarizes current knowledge of the cellular recognition mechanisms for FFAs, the inflammatory signaling pathways triggered by excess FFAs in obesity and the counteractive effects of both acute and chronic exercise on obesity-induced activation of inflammatory signaling pathways. A deeper understanding of the effects of exercise on inflammatory signaling pathways in obesity is useful to optimize preventive and therapeutic strategies to combat the increasing incidence of obesity and its comorbidities. Copyright © 2015 International Society of Exercise and Immunology. All rights reserved.

Disentangling stellar activity from exoplanetary signals with interferometry

Directory of Open Access Journals (Sweden)

Ligi Roxanne

2015-01-01

Full Text Available Stellar activity can express as many forms at stellar surfaces: dark spots, convective cells, bright plages. Particularly, dark spots and bright plages add noise on photometric data or radial velocity measurements used to detect exoplanets, and thus lead to false detection or disrupt their derived parameters. Since interferometry provides a very high angular resolution, it may constitute an interesting solution to distinguish the signal of a transiting exoplanet and that of stellar activity. It has also been shown that granulation adds bias in visibility and closure phase measurements, affecting in turn the derived stellar parameters. We analyze the noises generated by dark spots on interferometric observables and compare them to exoplanet signals. We investigate the current interferometric instruments able to measure and disentangle these signals, and show that there is a lack in spatial resolution. We thus give a prospective of the improvements to be brought on future interferometers, which would also significantly extend the number of available targets.

Robust Indoor Human Activity Recognition Using Wireless Signals

Directory of Open Access Journals (Sweden)

Yi Wang

2015-07-01

Full Text Available Wireless signals–based activity detection and recognition technology may be complementary to the existing vision-based methods, especially under the circumstance of occlusions, viewpoint change, complex background, lighting condition change, and so on. This paper explores the properties of the channel state information (CSI of Wi-Fi signals, and presents a robust indoor daily human activity recognition framework with only one pair of transmission points (TP and access points (AP. First of all, some indoor human actions are selected as primitive actions forming a training set. Then, an online filtering method is designed to make actions’ CSI curves smooth and allow them to contain enough pattern information. Each primitive action pattern can be segmented from the outliers of its multi-input multi-output (MIMO signals by a proposed segmentation method. Lastly, in online activities recognition, by selecting proper features and Support Vector Machine (SVM based multi-classification, activities constituted by primitive actions can be recognized insensitive to the locations, orientations, and speeds.

Grout treatment facility dangerous waste permit application

International Nuclear Information System (INIS)

1988-01-01

This section briefly describes the Hanford Site, provides a general description of the site operations and administration, provides an overview of the contents of this Grout Treatment Facility (GTF) Permit Application, and gives a list of acronyms and abbreviations used in the document. The decision was made to use the checklist as a locator reference instead of using the checklist section numbers as paragraph section numbers because several different types of waste management units, some of which are not addressed in the checklists, are part of the GTF. The GTF is a waste management unit within the Hanford Site facility. In May 1988, a permit application was filed that identified the GTF as an existing facility. The GTF mixes dry cementitious solids with liquid mixed wastes (containing both dangerous and radioactive constituents) produced by Hanford Site operations. In addition to the design and operating features of the GTF that are intended to meet the requirements of dangerous waste regulations, many additional design and operating features are necessary to comply with radioactive waste management practices. The GTF design features and practices are intended to keep operational exposure to radionuclides and dangerous substances ''as low as reasonably achievable'' (ALARA) and to provide a disposal system that protects the environment for at least 10,000 yr. In some instances, ALARA practices present difficulties when complying with requirements of dangerous waste regulations. This volume contains 2 appendices covering engineering drawings and operating procedures

Grout treatment facility dangerous waste permit application

International Nuclear Information System (INIS)

1988-01-01

This section briefly describes the Hanford Site, provides a general description of the site operations and administration, provides an overview of the contents of this Grout Treatment Facility (GTF) Permit Application, and gives a list of acronyms and abbreviations used in the document. The decision was made to use the checklist as a locator reference instead of using the checklist section numbers as paragraph section numbers because several different types of waste management units, some of which are not addressed in the checklists, are part of the GTF. The GTF is a waste management unit within the Hanford Site facility. In May 1988, a permit application was filed that identified the GTF as an existing facility. The GTF mixes dry cementitious solids with liquid mixed wastes (containing both dangerous and radioactive constitutents) produced by Hanford Site operations. In addition to the design and operating features of the GTF that are intended to meet the requirements of dangerous waste regulations, many additional design and operating features are necessary to comply with radioactive waste management practices. The GTF design features and practices are intended to keep operational exposure to radionuclides and dangerous substances ''as low as reasonably achievable'' (ALARA) and to provide a disposal system that protects the environment for at least 10,000 yr. In some instances, ALARA practices present difficulties when complying with requirements of dangerous waste regulations. This volume contains 2 Appendices covering engineering drawings and operating procedures

Grout Treatment Facility dangerous waste permit application

International Nuclear Information System (INIS)

1988-01-01

This section briefly describes the Hanford Site, provides a general description of the site operations and administration, provides an overview of the contents of this Grout Treatment Facility (GTF) Permit Application, and gives a list of acronyms and abbreviations used in the document. The decision was made to use the checklist as a locator reference instead of using the checklist section numbers as paragraph section numbers because several different types of waste management units, some of which are not addressed in the checklists, are part of the GTF. The GTF is a waste management unit within the Hanford Site facility. In May 1988, a permit application was filed that identified the GTF as an existing facility. The GTF mixes dry cementitious solids with liquid wastes (containing both dangerous and radioactive constituents) produced by Hanford Site operations. In addition to the design and operating features of the GTF that are intended to meet the requirements of dangerous waste regulations, many additional design and operating features are necessary to comply with radioactive waste management practices. The GTF design features and practices are intended to keep operational exposure to radionuclides and dangerous substances ''as low as reasonably achievable'' (ALARA) and to provide a disposal system that protects the environment for at least 10,000 yr. In some instances, ALARA practices present difficulties when complying with requirements of dangerous waste regulations. This volume contains 14 Appendices. Topics include Engineering Drawings, Maps, Roads, Toxicity Testing, and Pilot-Scale Testing

Reduced endogenous Ca2+ buffering speeds active zone Ca2+ signaling.

Science.gov (United States)

Delvendahl, Igor; Jablonski, Lukasz; Baade, Carolin; Matveev, Victor; Neher, Erwin; Hallermann, Stefan

2015-06-09

Fast synchronous neurotransmitter release at the presynaptic active zone is triggered by local Ca(2+) signals, which are confined in their spatiotemporal extent by endogenous Ca(2+) buffers. However, it remains elusive how rapid and reliable Ca(2+) signaling can be sustained during repetitive release. Here, we established quantitative two-photon Ca(2+) imaging in cerebellar mossy fiber boutons, which fire at exceptionally high rates. We show that endogenous fixed buffers have a surprisingly low Ca(2+)-binding ratio (∼ 15) and low affinity, whereas mobile buffers have high affinity. Experimentally constrained modeling revealed that the low endogenous buffering promotes fast clearance of Ca(2+) from the active zone during repetitive firing. Measuring Ca(2+) signals at different distances from active zones with ultra-high-resolution confirmed our model predictions. Our results lead to the concept that reduced Ca(2+) buffering enables fast active zone Ca(2+) signaling, suggesting that the strength of endogenous Ca(2+) buffering limits the rate of synchronous synaptic transmission.

Nutritive, Post-ingestive Signals Are the Primary Regulators of AgRP Neuron Activity

Directory of Open Access Journals (Sweden)

Zhenwei Su

2017-12-01

Full Text Available Summary: The brain regulates food intake by processing sensory cues and peripheral physiological signals, but the neural basis of this integration remains unclear. Hypothalamic, agouti-related protein (AgRP-expressing neurons are critical regulators of food intake. AgRP neuron activity is high during hunger and is rapidly reduced by the sight and smell of food. Here, we reveal two distinct components of AgRP neuron activity regulation: a rapid but transient sensory-driven signal and a slower, sustained calorie-dependent signal. We discovered that nutrients are necessary and sufficient for sustained reductions in AgRP neuron activity and that activity reductions are proportional to the calories obtained. This change in activity is recapitulated by exogenous administration of gut-derived satiation signals. Furthermore, we showed that the nutritive value of food trains sensory systems—in a single trial—to drive rapid, anticipatory AgRP neuron activity inhibition. Together, these data demonstrate that nutrients are the primary regulators of AgRP neuron activity. : Su et al. demonstrate that nutrient content in the GI tract is rapidly signaled to hypothalamic neurons activated by hunger. This rapid effect is mediated by three satiation signals that synergistically reduce the activity of AgRP neurons. These findings uncover how hunger circuits in the brain are regulated and raise the possibility that hunger can be pharmacologically controlled. Keywords: calcium imaging, AgRP neurons, calories, satiation signals, sensory regulation, single trial learning, cholecystokinin, CCK, peptide tyrosine tyrosine, PYY, amylin, homeostasis

Practices in the danger culture of late industrial society

NARCIS (Netherlands)

Rip, Arie; Motet, Gilles; Bieder, Corinne

2017-01-01

The chapter replaces the question of risk control by one about how we handle danger in our societies and realize a measure of safety. Ongoing practices in a framework of ‘danger cultures’ are the key. The case of environmental and health inspection and the intersecting ‘social worlds’ involved, are

Hanford facility dangerous waste permit application, 616 Nonradioactive Dangerous Waste Storage Facility. Revision 2A

International Nuclear Information System (INIS)

Bowman, R.C.

1994-04-01

This permit application for the 616 Nonradioactive Dangerous Waste Storage Facility consists for 15 chapters. Topics of discussion include the following: facility description and general provisions; waste characteristics; process information; personnel training; reporting and record keeping; and certification

Modelling human behaviours and reactions under dangerous environment

OpenAIRE

Kang, J; Wright, D K; Qin, S F; Zhao, Y

2005-01-01

This paper describes the framework of a real-time simulation system to model human behavior and reactions in dangerous environments. The system utilizes the latest 3D computer animation techniques, combined with artificial intelligence, robotics and psychology, to model human behavior, reactions and decision making under expected/unexpected dangers in real-time in virtual environments. The development of the system includes: classification on the conscious/subconscious behaviors and reactions...

Differing types of cellular phone conversations and dangerous driving.

Science.gov (United States)

Dula, Chris S; Martin, Benjamin A; Fox, Russell T; Leonard, Robin L

2011-01-01

This study sought to investigate the relationship between cell phone conversation type and dangerous driving behaviors. It was hypothesized that more emotional phone conversations engaged in while driving would produce greater frequencies of dangerous driving behaviors in a simulated environment than more mundane conversation or no phone conversation at all. Participants were semi-randomly assigned to one of three conditions: (1) no call, (2) mundane call, and, (3) emotional call. While driving in a simulated environment, participants in the experimental groups received a phone call from a research confederate who either engaged them in innocuous conversation (mundane call) or arguing the opposite position of a deeply held belief of the participant (emotional call). Participants in the no call and mundane call groups differed significantly only on percent time spent speeding and center line crossings, though the mundane call group consistently engaged in more of all dangerous driving behaviors than did the no call participants. Participants in the emotional call group engaged in significantly more dangerous driving behaviors than participants in both the no call and mundane call groups, with the exception of traffic light infractions, where there were no significant group differences. Though there is need for replication, the authors concluded that whereas talking on a cell phone while driving is risky to begin with, having emotionally intense conversations is considerably more dangerous. Copyright © 2010 Elsevier Ltd. All rights reserved.

EGF stimulates the activation of EGF receptors and the selective activation of major signaling pathways during mitosis.

Science.gov (United States)

Wee, Ping; Shi, Huaiping; Jiang, Jennifer; Wang, Yuluan; Wang, Zhixiang

2015-03-01

Mitosis and epidermal growth factor (EGF) receptor (EGFR) are both targets for cancer therapy. The role of EGFR signaling in mitosis has been rarely studied and poorly understood. The limited studies indicate that the activation of EGFR and downstream signaling pathways is mostly inhibited during mitosis. However, we recently showed that EGFR is phosphorylated in response to EGF stimulation in mitosis. Here we studied EGF-induced EGFR activation and the activation of major signaling pathways downstream of EGFR during mitosis. We showed that EGFR was strongly activated by EGF during mitosis as all the five major tyrosine residues including Y992, Y1045, Y1068, Y1086, and Y1173 were phosphorylated to a level similar to that in the interphase. We further showed that the activated EGFR is able to selectively activate some downstream signaling pathways while avoiding others. Activated EGFR is able to activate PI3K and AKT2, but not AKT1, which may be responsible for the observed effects of EGF against nocodazole-induced cell death. Activated EGFR is also able to activate c-Src, c-Cbl and PLC-γ1 during mitosis. However, activated EGFR is unable to activate ERK1/2 and their downstream substrates RSK and Elk-1. While it activated Ras, EGFR failed to fully activate Raf-1 in mitosis due to the lack of phosphorylation at Y341 and the lack of dephosphorylation at pS259. We conclude that contrary to the dogma, EGFR is activated by EGF during mitosis. Moreover, EGFR-mediated cell signaling is regulated differently from the interphase to specifically serve the needs of the cell in mitosis. Copyright © 2015 Elsevier Inc. All rights reserved.

Waste Encapsulation and Storage Facility (WESF) Dangerous Waste Training Plan (DWTP)

International Nuclear Information System (INIS)

SIMMONS, F.M.

2000-01-01

This Waste Encapsulation Storage Facility (WESF) Dangerous Waste Training Plan (DWTP) applies to personnel who perform work at, or in support of WESF. The plan, along with the names of personnel, may be given to a regulatory agency inspector upon request. General workers, subcontractors, or visiting personnel who have not been trained in the management of dangerous wastes must be accompanied by an individual who meets the requirements of this training plan. Dangerous waste management includes handling, treatment, storage, and/or disposal of dangerous and/or mixed waste. Dangerous waste management units covered by this plan include: less-than-90-day accumulation area(s); pool cells 1-8 and 12 storage units; and process cells A-G storage units. This training plan describes general requirements, worker categories, and provides course descriptions for operation of the WESF permitted miscellaneous storage units and the Less-than-90-Day Accumulation Areas

A Requirement for ZAK Kinase Activity in Canonical TGF-β Signaling

Directory of Open Access Journals (Sweden)

Shyam Nyati

2016-12-01

Full Text Available The sterile alpha motif and leucine zipper containing kinase ZAK (AZK, MLT, MLK7, is a MAPK-kinase kinase (MKKK. Like most MAPKKKs which are known to activate the c-Jun. amino-terminal kinase (JNK pathway, ZAK has been shown to participate in the transduction of Transforming growth factor-β (TGF-β-mediated non-canonical signaling. A role for ZAK in SMAD-dependent, canonical TGF-β signaling has not been previously appreciated. Using a combination of functional genomics and biochemical techniques, we demonstrate that ZAK regulates canonical TGFβRI/II signaling in lung and breast cancer cell lines and may serve as a key node in the regulation of TGFBR kinase activity. Remarkably, we demonstrate that siRNA mediated depletion of ZAK strongly inhibited TGF-β dependent SMAD2/3 activation and subsequent promoter activation (SMAD binding element driven luciferase expression; SBE4-Luc. A ZAK specific inhibitor (DHP-2, dose-dependently activated the bioluminescent TGFBR-kinase activity reporter (BTR, blocked TGF-β induced SMAD2/3 phosphorylation and SBE4-Luc activation and cancer cell-invasion. In aggregate, these findings identify a novel role for the ZAK kinase in canonical TGF-β signaling and an invasive cancer cell phenotype thus providing a novel target for TGF-β inhibition.

How common is within-plant signalling via volatiles?

DEFF Research Database (Denmark)

Li, Tao; Blande, James D.

2017-01-01

or neighbouring plants to impending danger. It has been postulated that HIPVs evolved for within-plant signalling and that other organisms subsequently evolved to use them. However, only seven studies have reported HIPV-mediated within-plant signalling, most conducted in the laboratory or greenhouse. This leaves...... open the ecological relevance and evolutionary underpinning of the phenomenon. We recently observed within-plant signalling in hybrid aspen under laboratory and field conditions. Greenhouse experiments showed that HIPVs mediated the process. While our study adds an aspen hybrid to the list of plants...... in which within-plant signalling has been demonstrated, we lack understanding of how common the process is and whether plants obtain fitness benefits....

Constructing mental illness as dangerous: a pilot study.

Science.gov (United States)

Wilson, C; Nairn, R; Coverdale, J; Panapa, A

1999-04-01

There is a dearth of studies examining how dangerousness is constructed in media depictions of mentally ill individuals who are frequently portrayed as acting violently. The aim of the present study was to identify the contribution of diverse technical, semiotic and discursive resources utilised in portraying a character with a mental illness in a prime-time drama as dangerous. Discourse analytic techniques, involving systematic, repeated, critical viewings, were applied to a single program drawn from a sample of prime-time television drama episodes touching on mental illness. Nine devices (appearance, music and sound effects, lighting, language, intercutting, jump-cutting, point of view shots, horror conventions and intertextuality) were identified as contributing to the signified dangerousness of person receiving care in the community for a mental illness. These techniques combine in signifying mental illness and a person suffering from it as dangerous. The findings suggest that mental health professionals working to reduce the stigma of mental illness need to have a reasonably sophisticated understanding of the practices and priorities of television production if they are to collaborate effectively with producers to create dramas that convey more human and sympathetic understandings of mental illness or to combat the negative effects of such portrayals.

Angiotensin II regulation of neuromodulation: downstream signaling mechanism from activation of mitogen-activated protein kinase.

Science.gov (United States)

Lu, D; Yang, H; Raizada, M K

1996-12-01

Angiotensin II (Ang II) stimulates expression of tyrosine hydroxylase and norepinephrine transporter genes in brain neurons; however, the signal-transduction mechanism is not clearly defined. This study was conducted to determine the involvement of the mitogen-activated protein (MAP) kinase signaling pathway in Ang II stimulation of these genes. MAP kinase was localized in the perinuclear region of the neuronal soma. Ang II caused activation of MAP kinase and its subsequent translocation from the cytoplasmic to nuclear compartment, both effects being mediated by AT1 receptor subtype. Ang II also stimulated SRE- and AP1-binding activities and fos gene expression and its translocation in a MAP kinase-dependent process. These observations are the first demonstration of a downstream signaling pathway involving MAP kinase in Ang II-mediated neuromodulation in noradrenergic neurons.

NLRP3 inflammasome: from a danger signal sensor to a regulatory node of oxidative stress and inflammatory diseases.

Science.gov (United States)

Abderrazak, Amna; Syrovets, Tatiana; Couchie, Dominique; El Hadri, Khadija; Friguet, Bertrand; Simmet, Thomas; Rouis, Mustapha

2015-01-01

IL-1β production is critically regulated by cytosolic molecular complexes, termed inflammasomes. Different inflammasome complexes have been described to date. While all inflammasomes recognize certain pathogens, it is the distinctive feature of NLRP3 inflammasome to be activated by many and diverse stimuli making NLRP3 the most versatile, and importantly also the most clinically implicated inflammasome. However, NLRP3 activation has remained the most enigmatic. It is not plausible that the intracellular NLRP3 receptor is able to detect all of its many and diverse triggers through direct interactions; instead, it is discussed that NLRP3 is responding to certain generic cellular stress-signals induced by the multitude of molecules that trigger its activation. An ever increasing number of studies link the sensing of cellular stress signals to a direct pathophysiological role of NLRP3 activation in a wide range of autoinflammatory and autoimmune disorders, and thus provide a novel mechanistic rational, on how molecules trigger and support sterile inflammatory diseases. A vast interest has created to unravel how NLRP3 becomes activated, since mechanistic insight is the prerequisite for a knowledge-based development of therapeutic intervention strategies that specifically target the NLRP3 triggered IL-1β production. In this review, we have updated knowledge on NLRP3 inflammasome assembly and activation and on the pyrin domain in NLRP3 that could represent a drug target to treat sterile inflammatory diseases. We have reported mutations in NLRP3 that were found to be associated with certain diseases. In addition, we have reviewed the functional link between NLRP3 inflammasome, the regulator of cellular redox status Trx/TXNIP complex, endoplasmic reticulum stress and the pathogenesis of diseases such as type 2 diabetes. Finally, we have provided data on NLRP3 inflammasome, as a critical regulator involved in the pathogenesis of obesity and cardiovascular diseases

The sounds of safety: stress and danger in music perception.

Science.gov (United States)

Schäfer, Thomas; Huron, David; Shanahan, Daniel; Sedlmeier, Peter

2015-01-01

As with any sensory input, music might be expected to incorporate the processing of information about the safety of the environment. Little research has been done on how such processing has evolved and how different kinds of sounds may affect the experience of certain environments. In this article, we investigate if music, as a form of auditory information, can trigger the experience of safety. We hypothesized that (1) there should be an optimal, subjectively preferred degree of information density of musical sounds, at which safety-related information can be processed optimally; (2) any deviation from the optimum, that is, both higher and lower levels of information density, should elicit experiences of higher stress and danger; and (3) in general, sonic scenarios with music should reduce experiences of stress and danger more than other scenarios. In Experiment 1, the information density of short music-like rhythmic stimuli was manipulated via their tempo. In an initial session, listeners adjusted the tempo of the stimuli to what they deemed an appropriate tempo. In an ensuing session, the same listeners judged their experienced stress and danger in response to the same stimuli, as well as stimuli exhibiting tempo variants. Results are consistent with the existence of an optimum information density for a given rhythm; the preferred tempo decreased for increasingly complex rhythms. The hypothesis that any deviation from the optimum would lead to experiences of higher stress and danger was only partly fit by the data. In Experiment 2, listeners should indicate their experience of stress and danger in response to different sonic scenarios: music, natural sounds, and silence. As expected, the music scenarios were associated with lowest stress and danger whereas both natural sounds and silence resulted in higher stress and danger. Overall, the results largely fit the hypothesis that music seemingly carries safety-related information about the environment.

Mechanisms and pathways of innate immune activation and regulation in health and cancer.

Science.gov (United States)

Cui, Jun; Chen, Yongjun; Wang, Helen Y; Wang, Rong-Fu

2014-01-01

Research on innate immune signaling and regulation has recently focused on pathogen recognition receptors (PRRs) and their signaling pathways. Members of PRRs sense diverse microbial invasions or danger signals, and initiate innate immune signaling pathways, leading to proinflammatory cytokines production, which, in turn, instructs adaptive immune response development. Despite the diverse functions employed by innate immune signaling to respond to a variety of different pathogens, the innate immune response must be tightly regulated. Otherwise, aberrant, uncontrolled immune responses will lead to harmful, or even fatal, consequences. Therefore, it is essential to better discern innate immune signaling and many regulators, controlling various signaling pathways, have been identified. In this review, we focus on the recent advances in our understanding of the activation and regulation of innate immune signaling in the host response to pathogens and cancer.

Treatment and disposal techniques of dangerous municipal solid wastes

International Nuclear Information System (INIS)

Beone, G.; Carbone, A.I.; Zagaroli, M.

1989-01-01

This paper describes the qualitative and quantitative features of the different types of dangerous municipal solid wastes, according to Italian law. In the second part the impact on environment and man health is presented. This impact should be minimized by suitable controlled disposal techniques, which differ from other municipal waste treatments. Finally, the paper deals with the most appropriate systems for treatment and disposal of such kind of waste. Particularly, some research activities in the field of metal recovery from used batteries, sponsored by ENEA, and carrying out by private companies, are described. (author)

EMPLOYING SENSOR NETWORK TO GUIDE FIREFIGHTERS IN DANGEROUS AREA

DEFF Research Database (Denmark)

Koohi, Hamidreza; Nadernejad, Ehsan; Fathi, Mahmoud

2010-01-01

In this paper, we intend to focus on the sensor network applications in firefighting. A distributed algorithm is developed for the sensor network to guide firefighters through a burning area. The sensor network models the danger of the area under coverage as obstacles, and has the property to adapt...... itself against possible changes. The protocol developed, will integrate the artificial potential field of the sensors with the information of the intended place of moving firefighter so that it guides the firefighter step by step through the sensor network by choosing the safest path in dangerous zones....... This protocol is simulated by Visual-Sense and the simulation results are available. Keyword: Firefighter, Sensor Network, Potential Field, Area’s Danger, Navigation...

Importance of leptin signaling and signal transducer and activator of transcription-3 activation in mediating the cardiac hypertrophy associated with obesity.

Science.gov (United States)

Leifheit-Nestler, Maren; Wagner, Nana-Maria; Gogiraju, Rajinikanth; Didié, Michael; Konstantinides, Stavros; Hasenfuss, Gerd; Schäfer, Katrin

2013-07-11

The adipokine leptin and its receptor are expressed in the heart, and leptin has been shown to promote cardiomyocyte hypertrophy in vitro. Obesity is associated with hyperleptinemia and hypothalamic leptin resistance as well as an increased risk to develop cardiac hypertrophy and heart failure. However, the role of cardiac leptin signaling in mediating the cardiomyopathy associated with increased body weight is unclear, in particular, whether it develops subsequently to cardiac leptin resistance or overactivation of hypertrophic signaling pathways via elevated leptin levels. The cardiac phenotype of high-fat diet (HFD)-induced obese wildtype (WT) mice was examined and compared to age-matched genetically obese leptin receptor (LepR)-deficient (LepRdb/db) or lean WT mice. To study the role of leptin-mediated STAT3 activation during obesity-induced cardiac remodeling, mice in which tyrosine residue 1138 within LepR had been replaced with a serine (LepRS1138) were also analyzed. Obesity was associated with hyperleptinemia and elevated cardiac leptin expression in both diet-induced and genetically obese mice. Enhanced LepR and STAT3 phosphorylation levels were detected in hearts of obese WT mice, but not in those with LepR mutations. Moreover, exogenous leptin continued to induce cardiac STAT3 activation in diet-induced obese mice. Although echocardiography revealed signs of cardiac hypertrophy in all obese mice, the increase in left ventricular (LV) mass and diameter was significantly more pronounced in LepRS1138 animals. LepRS1138 mice also exhibited an increased activation of signaling proteins downstream of LepR, including Jak2 (1.8-fold), Src kinase (1.7-fold), protein kinase B (1.3-fold) or C (1.6-fold). Histological analysis of hearts revealed that the inability of leptin to activate STAT3 in LepRdb/db and LepRS1138 mice was associated with reduced cardiac angiogenesis as well as increased apoptosis and fibrosis. Our findings suggest that hearts from obese mice

Cholesterol activates the G-protein coupled receptor Smoothened to promote Hedgehog signaling

Science.gov (United States)

Luchetti, Giovanni; Sircar, Ria; Kong, Jennifer H; Nachtergaele, Sigrid; Sagner, Andreas; Byrne, Eamon FX; Covey, Douglas F; Siebold, Christian; Rohatgi, Rajat

2016-01-01

Cholesterol is necessary for the function of many G-protein coupled receptors (GPCRs). We find that cholesterol is not just necessary but also sufficient to activate signaling by the Hedgehog (Hh) pathway, a prominent cell-cell communication system in development. Cholesterol influences Hh signaling by directly activating Smoothened (SMO), an orphan GPCR that transmits the Hh signal across the membrane in all animals. Unlike many GPCRs, which are regulated by cholesterol through their heptahelical transmembrane domains, SMO is activated by cholesterol through its extracellular cysteine-rich domain (CRD). Residues shown to mediate cholesterol binding to the CRD in a recent structural analysis also dictate SMO activation, both in response to cholesterol and to native Hh ligands. Our results show that cholesterol can initiate signaling from the cell surface by engaging the extracellular domain of a GPCR and suggest that SMO activity may be regulated by local changes in cholesterol abundance or accessibility. DOI: http://dx.doi.org/10.7554/eLife.20304.001 PMID:27705744

The Economic Side Effects of Dangerous Drug Announcements.

OpenAIRE

Dranove, David; Olsen, Chris

1994-01-01

Immediately prior to the passage of the 1962 Food and Drug Administration Amendments, there were a number of drugs recalled from markets worldwide. Announcements about the dangerous side effects of these drugs were associated with lower-share prices for their manufacturers and the industry as a whole. We perform several analyses to sort out alternative explanations for the observed declines. We find that dangerous drug announcements had no effect on the sales of other drugs and didn't affect ...

IMPROVING METHODOLOGY OF RISK IDENTIFICATION OF OCCUPATIONAL DANGEROUS

Directory of Open Access Journals (Sweden)

A. P. BOCHKOVSKYI

2018-04-01

Full Text Available In the paper, according to the analysis of statistical data, correlation between the amount of occupational injuries and occupationaldiseases in Ukraine within last 5 years is defined. Also, using methodology of the International Labor Organizationcorrelcation between the amount of accident fatalities and general number of accidents in Ukraine and EU countries (Austria, GreatBritain, Germany, Denmark, Norway, Poland, Hungry, Finland, France is defined. It is shown that in spite of the positive dynamicsof decreasing amount of occupational injuries, the number of occupational diseases in Ukraine always increases. The comparativeanalysis of the ratio of the number of accident fatalities to the total number of registered accidents showed that, on average, Ukraineexceeds the EU countries by this indicator by 100 times.It is noted, that such negative indicators (in particular, increasing amount of occupational diseases, may occure because ofimperfect methodology for identifying the risks of professional dangerous.Also, it is ascertained that basing on the existed methodology, the identefication process of occupational dangerous isquite subjective, which reduces objectivity of conducting quantitative assessment. In order to eliminate defined drawnbacks it is firsttime proposed to use corresponding integral criterion to conduct the process of quantitative risk assessmentTo solve this problem authors formulate and propose an algorithm of improving methodology of a process of analysing dangerousand harmful production effects (DHPE which are the mainest reasons of occupational dangerous.The proposed algorithm includes implementation of four following successive steps: DHPE identification, indication of theirmaximum allowed threshold of concentrations (levels, identification of the sources of identified DHPE, esimation of consequencesof manifestation.The improved proposed methodology allows indentify risks of occurrence occupational dangerous in systems

Boehmenan, a lignan from Hibiscus ficulneus, showed Wnt signal inhibitory activity.

Science.gov (United States)

Shono, Takumi; Ishikawa, Naoki; Toume, Kazufumi; Arai, Midori A; Ahmed, Firoj; Sadhu, Samir K; Ishibashi, Masami

2015-07-15

The Wnt signal pathway modulates numerous biological processes, and its aberrant activation is related to various diseases. Therefore, inhibition of the Wnt signal may provide an effective (or efficient) strategy for these diseases. Cell-based luciferase assay targeting the Wnt signal (TOP assay) revealed that Hibiscus ficulneus extract inhibited the Wnt signal. The activity-guided isolation of the MeOH extract of H. ficulneus stems yielded four known (1-4) lignans along with myriceric acid (5). Compounds 1-4 potently inhibited the Wnt signal with TOPflash IC50 values of 1.0, 4.5, 6.3, and 1.9 μM, respectively. Compound 1 exhibited cytotoxicity against both Wnt-dependent (HCT116) and Wnt-independent (RKO) cells. Western blot analysis showed that 1 decreased the expression of full, cytosolic and nuclear β-catenin along with c-myc in STF/293 cells. Our results suggested that 1 may have inhibited the Wnt signal by decreasing β-catenin levels. Copyright © 2015 Elsevier Ltd. All rights reserved.

The dangers of sports journalism

DEFF Research Database (Denmark)

Sparre, Kirsten

2017-01-01

According to The Committee to Protect Journalists, 2 per cent of all journalists killed since 1992 worked on the sports beat. However, at present there is little understanding of the specific dangers faced by sports journalists. This chapter presents findings from exploratory research on 78 repor...

mTOR signaling promotes stem cell activation via counterbalancing BMP-mediated suppression during hair regeneration.

Science.gov (United States)

Deng, Zhili; Lei, Xiaohua; Zhang, Xudong; Zhang, Huishan; Liu, Shuang; Chen, Qi; Hu, Huimin; Wang, Xinyue; Ning, Lina; Cao, Yujing; Zhao, Tongbiao; Zhou, Jiaxi; Chen, Ting; Duan, Enkui

2015-02-01

Hair follicles (HFs) undergo cycles of degeneration (catagen), rest (telogen), and regeneration (anagen) phases. Anagen begins when the hair follicle stem cells (HFSCs) obtain sufficient activation cues to overcome suppressive signals, mainly the BMP pathway, from their niche cells. Here, we unveil that mTOR complex 1 (mTORC1) signaling is activated in HFSCs, which coincides with the HFSC activation at the telogen-to-anagen transition. By using both an inducible conditional gene targeting strategy and a pharmacological inhibition method to ablate or inhibit mTOR signaling in adult skin epithelium before anagen initiation, we demonstrate that HFs that cannot respond to mTOR signaling display significantly delayed HFSC activation and extended telogen. Unexpectedly, BMP signaling activity is dramatically prolonged in mTOR signaling-deficient HFs. Through both gain- and loss-of-function studies in vitro, we show that mTORC1 signaling negatively affects BMP signaling, which serves as a main mechanism whereby mTORC1 signaling facilitates HFSC activation. Indeed, in vivo suppression of BMP by its antagonist Noggin rescues the HFSC activation defect in mTORC1-null skin. Our findings reveal a critical role for mTOR signaling in regulating stem cell activation through counterbalancing BMP-mediated repression during hair regeneration. © The Author (2015). Published by Oxford University Press on behalf of Journal of Molecular Cell Biology, IBCB, SIBS, CAS. All rights reserved.

Coco is a dual activity modulator of TGFβ signaling

Science.gov (United States)

Deglincerti, Alessia; Haremaki, Tomomi; Warmflash, Aryeh; Sorre, Benoit; Brivanlou, Ali H.

2015-01-01

The TGFβ signaling pathway is a crucial regulator of developmental processes and disease. The activity of TGFβ ligands is modulated by various families of soluble inhibitors that interfere with the interactions between ligands and receptors. In an unbiased, genome-wide RNAi screen to identify genes involved in ligand-dependent signaling, we unexpectedly identified the BMP/Activin/Nodal inhibitor Coco as an enhancer of TGFβ1 signaling. Coco synergizes with TGFβ1 in both cell culture and Xenopus explants. Molecularly, Coco binds to TGFβ1 and enhances TGFβ1 binding to its receptor Alk5. Thus, Coco acts as both an inhibitor and an enhancer of signaling depending on the ligand it binds. This finding raises the need for a global reconsideration of the molecular mechanisms regulating TGFβ signaling. PMID:26116664

Feeding-Danger Trade-Offs Underlie Stopover Site Selection by Migrants

Directory of Open Access Journals (Sweden)

Andrea C. Pomeroy

2008-06-01

Full Text Available To migrate successfully, birds need to store adequate fat reserves to fuel each leg of the journey. Migrants acquire their fuel reserves at stopover sites; this often entails exposure to predators. Therefore, the safety attributes of sites may be as important as the feeding opportunities. Furthermore, site choice might depend on fuel load, with lean birds more willing to accept danger to obtain good feeding. Here, we evaluate the factors underlying stopover-site usage by migrant Western Sandpipers (Calidris mauri on a landscape scale. We measured the food and danger attributes of 17 potential stopover sites in the Strait of Georgia and Puget Sound region. We used logistic regression models to test whether food, safety, or both were best able to predict usage of these sites by Western Sandpipers. Eight of the 17 sites were used by sandpipers on migration. Generally, sites that were high in food and safety were used, whereas sites that were low in food and safety were not. However, dangerous sites were used if there was ample food abundance, and sites with low food abundance were used if they were safe. The model including both food and safety best-predicted site usage by sandpipers. Furthermore, lean sandpipers used the most dangerous sites, whereas heavier birds (which do not need to risk feeding in dangerous locations used safer sites. This study demonstrates that both food and danger attributes are considered by migrant birds when selecting stopover sites, thus both these attributes should be considered to prioritize and manage stopover sites for conservation.

VEGFR-3 signaling is regulated by a G-protein activator, activator of G-protein signaling 8, in lymphatic endothelial cells.

Science.gov (United States)

Sakima, Miho; Hayashi, Hisaki; Mamun, Abdullah Al; Sato, Motohiko

2018-07-01

Vascular endothelial growth factor C (VEGFC) and its cognate receptor VEGFR-3 play a key role in lymphangiogenesis. We previously reported that an ischemia-inducible Gβγ signal regulator, activator of G-protein signaling 8 (AGS8), regulated the subcellular distribution of vascular endothelial growth factor receptor-2 (VEGFR-2) and influenced VEGFA-induced signaling in vascular endothelial cells. Here, we report that AGS8 regulates VEGFR-3, which is another subtype of the VEGF receptor family, and mediates VEGFC signaling in human dermal lymphatic endothelial cells (HDLECs). VEGFC stimulated the proliferation of HDLECs and tube formation by HDLECs, which were inhibited by knocking down AGS8 by small interfering RNA (siRNA). AGS8 siRNA inhibited VEGFC-mediated phosphorylation of VEGFR-3 and its downstream molecules, including ERK1/2 and AKT. Analysis of fluorescence-activated cell sorting and immunofluorescence staining demonstrated that AGS8 knockdown was associated with a reduction of VEGFR-3 at the cell surface. Endocytosis inhibitors did not rescue the decrease of cell-surface VEGFR-3, suggesting that AGS8 regulated the trafficking of VEGFR-3 to the plasma membrane. An immunoprecipitation assay indicated that VEGFR-3 formed a complex including AGS8 and Gβγ in cells. These data suggest the novel regulation of VEGFC-VEGFR-3 by AGS8 in HDLECs and a potential role for AGS8 in lymphangiogenesis. Copyright © 2018 Elsevier Inc. All rights reserved.

Regulations concerning marine transport and storage of dangerous things (abridged)

International Nuclear Information System (INIS)

1981-01-01

When the dangerous things of different classes or items are loaded on a same ship, they shall be separated mutually according to the specified standards. Containers shall be cleaned well before loading dangerous things. When there is the danger of heating, gasification, corrosion and other critical physical or chemical processes by the mutual action of the dangerous things of different items or dangerous things and other goods, they must not be loaded in a same container. Basic terms are defined, such as radioactive transported goods, fissile transported goods and exclusive loading. Radioactive transported goods are classified into types of L, A, BM and BU, and fissile transported goods into 3 kinds. Each type of these goods is defined in size and radioactivity. When the makers of radioactive transported goods pack radioactive materials into the transported goods of type BM or BU, they shall get before shipment the confirmation of the Minister of Transport concerning the standard to which these goods conform. The maximum radiation dose rate must not exceed 200 milli-rem an hour on the surface and 10 milli-rem an hour at the distance of 1 meter from the surfaces of containers loaded with radioactive transported goods. Signs, the limit of shipment and other related matters are prescribed in detail. (Okada, K.)

Regulations concerning marine transport and storage of dangerous things (abridged)

International Nuclear Information System (INIS)

1985-01-01

When the dangerous things of different classes or items are loaded on a same ship, they shall be separated mutually according to the specified standards. Containers shall be cleaned well before loading dangerous things. When there is the danger of heating, gasification, corrosion and other critical physical or chemical processes by the mutual action of the dangerous things of different items or dangerous things and other goods, they must not be loaded in a same container. Basic terms are defined, such as radioactive transported goods, fissile transported goods and exclusive loading. Radioactive transported goods are classified into types of L, A, BM and BU, and fissile transported goods into 3 kinds. Each type of these goods is defined in size and radioactivity. When the makers of radioactive transported goods pack radioactive materials into the transported goods of type BM or BU, they shall get before shipment the confirmation of the Minister of Transport concerning the standard to which these goods conform. The maximum radiation dose rate must not exceed 200 milli-rem an hour on the surface and 10 milli-rem an hour at the distance of 1 meter from the surfaces of containers loaded with radioactive transported goods. Signs, the limit of shipment and other related matters are prescribed in detail. (Kubozono, M.)

Outer Membrane Protein 25 of Brucella Activates Mitogen-Activated Protein Kinase Signal Pathway in Human Trophoblast Cells

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Jing Zhang

2017-12-01

Full Text Available Outer membrane protein 25 (OMP25, a virulence factor from Brucella, plays an important role in maintaining the structural stability of Brucella. Mitogen-activated protein kinase (MAPK signal pathway widely exists in eukaryotic cells. In this study, human trophoblast cell line HPT-8 and BALB/c mice were infected with Brucella abortus 2308 strain (S2308 and 2308ΔOmp25 mutant strain. The expression of cytokines and activation of MAPK signal pathway were detected. We found that the expressions of tumor necrosis factor-α, interleukin-1, and interleukin-10 (IL-10 were increased in HPT-8 cells infected with S2308 and 2308ΔOmp25 mutant. S2308 also activated p38 phosphorylation protein, extracellular-regulated protein kinases (ERK, and Jun-N-terminal kinase (JNK from MAPK signal pathway. 2308ΔOmp25 could not activate p38, ERK, and JNK branches. Immunohistochemistry experiments showed that S2308 was able to activate phosphorylation of p38 and ERK in BABL/c mice. However, 2308ΔOmp25 could weakly activate phosphorylation of p38 and ERK. These results suggest that Omp25 played an important role in the process of Brucella activation of the MAPK signal pathway.

Chemokines: a new dendritic cell signal for T cell activation

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Christoph A Thaiss

2011-08-01

Full Text Available Dendritic cells (DCs are the main inducers and regulators of cytotoxic T lymphocyte (CTL responses against viruses and tumors. One checkpoint to avoid misguided CTL activation, which might damage healthy cells of the body, is the necessity for multiple activation signals, involving both antigenic as well as additional signals that reflect the presence of pathogens. DCs provide both signals when activated by ligands of pattern recognition receptors and licensed by helper lymphocytes. Recently, it has been established that such T cell licensing can be facilitated by CD4+ T helper cells (classical licensing or by NKT cells (alternative licensing. Licensing regulates the DC/CTL cross-talk at multiple layers. Direct recruitment of CTLs through chemokines released by licensed DCs has recently emerged as a common theme and has a crucial impact on the efficiency of CTL responses. Here, we discuss recent advances in our understanding of DC licensing for cross-priming and implications for the temporal and spatial regulation underlying this process. Future vaccination strategies will benefit from a deeper insight into the mechanisms that govern CTL activation.

Reward acts as a signal to control delay-period activity in delayed-response tasks.

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Ichihara-Takeda, Satoe; Takeda, Kazuyoshi; Funahashi, Shintaro

2010-03-31

Prefrontal delay-period activity represents a neural mechanism for the active maintenance of information and needs to be controlled by some signal to appropriately operate working memory. To examine whether reward-delivery acts as this signal, the effects of delay-period activity in response to unexpected reward-delivery were examined by analyzing single-neuron activity recorded in the primate dorsolateral prefrontal cortex. Among neurons that showed delay-period activity, 34% showed inhibition of this activity in response to unexpected reward-delivery. The delay-period activity of these neurons was affected by the expectation of reward-delivery. The strength of the reward signal in controlling the delay-period activity is related to the strength of the effect of reward information on the delay-period activity. These results indicate that reward-delivery acts as a signal to control delay-period activity.

Andrographolide suppresses TRIF-dependent signaling of toll-like receptors by targeting TBK1.

Science.gov (United States)

Kim, Ah-Yeon; Shim, Hyun-Jin; Shin, Hyeon-Myeong; Lee, Yoo Jung; Nam, Hyeonjeong; Kim, Su Yeon; Youn, Hyung-Sun

2018-04-01

Toll-like receptors (TLRs) play a crucial role in danger recognition and induction of innate immune response against bacterial and viral infections. The TLR adaptor molecule, toll-interleukin-1 receptor domain-containing adapter inducing interferon-β (TRIF), facilitates TLR3 and TLR4 signaling, leading to the activation of the transcription factor, NF-κB and interferon regulatory factor 3 (IRF3). Andrographolide, the active component of Andrographis paniculata, exerts anti-inflammatory effects; however, the principal molecular mechanisms remain unclear. The objective of this study was to investigate the role of andrographolide in TLR signaling pathways. Andrographolide suppressed NF-κB activation as well as COX-2 expression induced by TLR3 or TLR4 agonists. Andrographolide also suppressed the activation of IRF3 and the expression of interferon inducible protein-10 (IP-10) induced by TLR3 or TLR4 agonists. Andrographolide attenuated ligand-independent activation of IRF3 following overexpression of TRIF, TBK1, or IRF3. Furthermore, andrographolide inhibited TBK1 kinase activity in vitro. These results indicate that andrographolide modulates the TRIF-dependent pathway of TLRs by targeting TBK1 and represents a potential new anti-inflammatory candidate. Copyright © 2018 Elsevier B.V. All rights reserved.

Regulations concerning marine transport and storage of dangerous things (abridged)

International Nuclear Information System (INIS)

1987-01-01

This report shows the Ordinances No.84 (1967) and No.30 (1957) of the Ministry of transport. The Ordinance No.84 has been published in detail elsewhere. The provisions concerning shipping transport and storage of dangerous substances deal with isolation of each dangerous substance, method for loading (cleaning of container, etc.), certificate for ship for transporting dangerous substances, renewal of certificate for ship for transporting dangerous substances, return of certificate, fee (for renewal and reissue of certificate), definition of terms, type of radioactive cargo (L-type cargo, A-type cargo, BM-type cargo, BU type cargo), transport of radioactive substances, type of fissionable cargo (Type I, Type II and Type III), confirmation of safety concerning radioactive cargo (conformity to standards, inspection, approval, etc.), limit of cargo volume, transport index, marking (type of cargo), confirmation of safety of transport, inspection of contamination, notice of transport, special measures, inspection of cargo (radioactive substances), requirements for container and package, etc. (Nogami, K.)

Co-Evolution of Social Learning and Evolutionary Preparedness in Dangerous Environments.

Science.gov (United States)

Lindström, Björn; Selbing, Ida; Olsson, Andreas

2016-01-01

Danger is a fundamental aspect of the lives of most animals. Adaptive behavior therefore requires avoiding actions, objects, and environments associated with danger. Previous research has shown that humans and non-human animals can avoid such dangers through two types of behavioral adaptions, (i) genetic preparedness to avoid certain stimuli or actions, and (ii) social learning. These adaptive mechanisms reduce the fitness costs associated with danger but still allow flexible behavior. Despite the empirical prevalence and importance of both these mechanisms, it is unclear when they evolve and how they interact. We used evolutionary agent-based simulations, incorporating empirically based learning mechanisms, to clarify if preparedness and social learning typically both evolve in dangerous environments, and if these mechanisms generally interact synergistically or antagonistically. Our simulations showed that preparedness and social learning often co-evolve because they provide complimentary benefits: genetic preparedness reduced foraging efficiency, but resulted in a higher rate of survival in dangerous environments, while social learning generally came to dominate the population, especially when the environment was stochastic. However, even in this case, genetic preparedness reliably evolved. Broadly, our results indicate that the relationship between preparedness and social learning is important as it can result in trade-offs between behavioral flexibility and safety, which can lead to seemingly suboptimal behavior if the evolutionary environment of the organism is not taken into account.

Regulations concerning marine transport and storage of dangerous things (abridged)

International Nuclear Information System (INIS)

1979-01-01

Basic terms are explained, such as: radioactive load; fissionable load; exclusive loading; and container. Radioactive loads are classified into four types - L, A, BM and BU, and fissionable loads into three kinds - the 1st, 2nd and 3rd. Maximum radiation dose of radioactive loads in containers shall not exceed 200 mili-rem for an hour at the surface of containers and 10 mili-rem for an hour at a distance of 1 meter from the surface. Specified signals or indications shall be attached to radioactive loads or containers with them. Letters of exclusive loading or ''FULL LOAD'' shall be marked on the signals in exclusive loading. Captains shall file to the Minister of Transportation before shipment a transport program to transfer BM or BU loads or fissionable loads of the 3rd kind, and get confirmation of safety by the minister. Captains shall restrict entrance of persons other than the staff concerned to the place where radioactive materials are laid by setting up off-limits. Maximum doses shall not go over 0.18 mili-rem for an hour on board in living areas or places regularly used. Mutual separation, method of enclosing and loading of dangerous things, transport index, limit of loading and others are stipulated in detail. (Okada, K.)

LIF-activated Jak signaling determines Esrrb expression during late-stage reprogramming

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Delun Huang

2018-01-01

Full Text Available The regulatory process of naïve-state induced pluripotent stem cell (iPSC generation is not well understood. Leukemia inhibitory factor (LIF-activated Janus kinase/signal transducer and activator of transcription 3 (Jak/Stat3 is the master regulator for naïve-state pluripotency achievement and maintenance. The estrogen-related receptor beta (Esrrb serves as a naïve-state marker gene regulating self-renewal of embryonic stem cells (ESCs. However, the interconnection between Esrrb and LIF signaling for pluripotency establishment in reprogramming is unclear. We screened the marker genes critical for complete reprogramming during mouse iPSC generation, and identified genes including Esrrb that are responsive to LIF/Jak pathway signaling. Overexpression of Esrrb resumes the reprogramming halted by inhibition of Jak activity in partially reprogrammed cells (pre-iPSCs, and leads to the generation of pluripotent iPSCs. We further show that neither overexpression of Nanog nor stimulation of Wnt signaling, two upstream regulators of Esrrb in ESCs, stimulates the expression of Esrrb in reprogramming when LIF or Jak activity is blocked. Our study demonstrates that Esrrb is a specific reprogramming factor regulated downstream of the LIF/Jak signaling pathway. These results shed new light on the regulatory role of LIF pathway on complete pluripotency establishment during iPSC generation.

Immune Homeostasis in Epithelial Cells: Evidence and Role of Inflammasome Signaling Reviewed.

Science.gov (United States)

Peeters, Paul M; Wouters, Emiel F; Reynaert, Niki L

2015-01-01

The epithelium regulates the interaction between the noxious xenogenous, as well as the microbial environment and the immune system, not only by providing a barrier but also by expressing a number of immunoregulatory membrane receptors, and intracellular danger sensors and their downstream effectors. Amongst these are a number of inflammasome sensor subtypes, which have been initially characterized in myeloid cells and described to be activated upon assembly into multiprotein complexes by microbial and environmental triggers. This review compiles a vast amount of literature that supports a pivotal role for inflammasomes in the various epithelial barriers of the human body as essential factors maintaining immune signaling and homeostasis.

Cessation of dangerousness status: an analysis of 224 reports from the Instituto de Perícias Heitor Carrilho, Rio de Janeiro, Brazil

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Gustavo C. Oliveira

Full Text Available Objectives: To evaluate factors related to dangerousness cessation at the end of involuntary commitment based on an analysis of expert reports. In light of the current legal requirement of dangerousness cessation as a pre-requisite for prison or internment release of individuals subjected to the safety measure, we sought elements to reflect on the practice of expert examiners in charge of making this decision. Methods: The authors revised 224 expert psychiatric dangerousness cessation reports released 2011 through 2014 and collected data for a statistical analysis. Results: The following variables were associated with positive risk cessation assessments: no inadequate behavior (according to the assistant professionals, no productive psychotic symptoms, no negative symptoms, presence of insight, presence of a support network, and no psychoactive substance abuse. The following variables were associated with negative dangerousness cessation decisions: early onset of malfunction, lack of insight, negative attitudes, active signs of major mental illness, presence of impulsiveness, poor response to treatment, presence of plans lacking feasibility, exposure to destabilizing factors, lack of personal support, and presence of stress. Conclusions: In this study we were able to identify factors associated with dangerousness in a sample of expert reports. The knowledge of factors linked to a higher risk of recidivism in illegal activities or violent behavior is crucial for decision-making regarding the release of offenders after their legally established period of involuntary commitment.

The satiety signaling neuropeptide perisulfakinin inhibits the activity of central neurons promoting general activity

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Dieter Wicher

2007-12-01

Full Text Available The metabolic state is one of the determinants of the general activity level. Satiety is related to resting or sleep whereas hunger correlates to wakefulness and activity. The counterpart to the mammalian satiety signal cholecystokinin (CCK in insects are the sulfakinins. The aim of this study was to resolve the mechanism by which the antifeedant activity of perisulfakinin (PSK in Periplaneta americana is mediated. We identified the sources of PSK which is used both as hormone and as paracrine messenger. PSK is found in the neurohemal organ of the brain and in nerve endings throughout the central nervous system. To correlate the distributions of PSK and its receptor (PSKR, we cloned the gene coding for PSKR and provide evidence for its expression within the nervous system. It occurs only in a few neurons, among them are the dorsal unpaired median (DUM neurons which release octopamine thereby regulating the general level of activity. Application of PSK to DUM neurons attenuated the spiking frequency (EC50=11pM due to reduction of a pacemaker Ca2+ current through cAMP-inhibited pTRPγ channels. PSK increased the intracellular cAMP level while decreasing the intracellular Ca2+ concentration in DUM neurons. Thus, the satiety signal conferred by PSK acts antagonistically to the hunger signal, provided by the adipokinetic hormone (AKH: PSK depresses the electrical activity of DUM neurons by inhibiting the pTRPγ channel that is activated by AKH under conditions of food shortage.

Towards brain-activity-controlled information retrieval: Decoding image relevance from MEG signals.

Science.gov (United States)

Kauppi, Jukka-Pekka; Kandemir, Melih; Saarinen, Veli-Matti; Hirvenkari, Lotta; Parkkonen, Lauri; Klami, Arto; Hari, Riitta; Kaski, Samuel

2015-05-15

We hypothesize that brain activity can be used to control future information retrieval systems. To this end, we conducted a feasibility study on predicting the relevance of visual objects from brain activity. We analyze both magnetoencephalographic (MEG) and gaze signals from nine subjects who were viewing image collages, a subset of which was relevant to a predetermined task. We report three findings: i) the relevance of an image a subject looks at can be decoded from MEG signals with performance significantly better than chance, ii) fusion of gaze-based and MEG-based classifiers significantly improves the prediction performance compared to using either signal alone, and iii) non-linear classification of the MEG signals using Gaussian process classifiers outperforms linear classification. These findings break new ground for building brain-activity-based interactive image retrieval systems, as well as for systems utilizing feedback both from brain activity and eye movements. Copyright © 2015 Elsevier Inc. All rights reserved.

[Responsibilities of enterprises introducing new dangerous chemical substances and preparations].

Science.gov (United States)

Cieśla, Jacek; Majka, Jerzy

2004-01-01

The paper reviews the responsibilities of producers, importers and distributors set in a new Act of January 2001 on chemical substances and preparations (Off. J. 2001, No. 11, item 84, with subsequent amendments). This Act together with executive provisions is aimed at harmonizing Polish legislation with EU requirements. The Act sets conditions, restriction and bans of production placing on the market and use of chemical substances and preparations in order to protect human health and environment against their harmful effects. The Act together with a number of executive provisions render those who introduce dangerous chemicals and chemical preparations, including distributors responsible for: classification and labelling of dangerous chemical substances and preparations; possessing, making available and up-dating safety data sheets; supplying packages containing certain dangerous substances with child-proof fastenings; notifying the Inspector for Chemical Substances and Preparations about placing a dangerous preparation on the market; notifying the Inspector about a new substance and conducting required studies; being properly qualified to handle dangerous substances. The Act strictly defines the term "placing a substance or a preparation on the market"--it means making a substance or a preparation available to third parties on the territory of The Republic of Poland, territories of the Member States of the European Union or the territory of Iceland, Liechtenstein and Norway, unless the Act provides otherwise; it also means introduction of a substance or a preparation from outside of the territory referred to above on the customs territory of The Republic of Poland, or that of the member states of the European Union and other states listed above. In addition, some of the responsibilities defined by the provisions of the law on chemical substances and preparations are also applicable to handling of biocidals, which are classified as dangerous substances. The Act

(Neuro)predictions, Dangerousness, and Retributivism

DEFF Research Database (Denmark)

Petersen, Thomas Søbirk

2014-01-01

Through the criminal justice system so-called dangerous offenders are, besides the offence that they are being convicted of and sentenced to, also punished for acts that they have not done but that they are believe to be likely to commit in the future. The aim of this paper is to critically discu...

[The dangers of blue light: True story!].

Science.gov (United States)

Renard, G; Leid, J

2016-05-01

The dangers of the blue light are the object of numerous publications, for both the scientific community and the general public. The new prolific development of light sources emitting potentially toxic blue light (415-455nm) ranges from LED (Light Emitting Diodes) lamps for interior lighting to television screens, computers, digital tablets and smartphones using OLED (Organic Light Emitting Diode) or AMOLED (Active-Matrix Organic Light Emitting Diode) technology. First we will review some technical terms and the main characteristics of light perceived by the human eye. Then we will discuss scientific proof of the toxicity of blue light to the eye, which may cause cataract or macular degeneration. Analysis of the light spectra of several light sources, from natural light to LED lamps, will allow us to specify even better the dangers related to each light source. LED lamps, whether used as components for interior lighting or screens, are of concern if they are used for extended viewing times and at short distance. While we can protect ourselves from natural blue light by wearing colored glasses which filter out, on both front and back surfaces, the toxic wavelengths, it is more difficult to protect oneself from LED lamps in internal lighting, the use of which should be restricted to "white warmth" lamps (2700K). As far as OLED or AMOLED screens are concerned, the only effective protection consists of using them occasionally and only for a short period of time. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Children's recognition of dangerous household products: child development and poisoning risk.

Science.gov (United States)

Schwebel, David C; Wells, Hayley; Johnston, Anna

2015-03-01

Preliterate children may be poisoned because they fail to distinguish safe versus hazardous household products. Study 1: A total of 228 children aged 18-54 months completed four tasks assessing ability to recognize product safety. Study 2: A total of 68 children aged 17-31 months chose products to drink from pairs of dangerous versus beverage bottles. Study 3: A total of 119 children aged 18-42 months sorted 12 objects into toys, things you can drink, and things that are bad/dangerous. Left alone, children frequently touched dangerous household products. Children frequently misidentified poisonous products as safe. Some developmental trends emerged. The following packaging features apparently helped children recognize danger: black bottle color; opaque packaging; salient symbols like insects; lack of pointy spouts; squared, not round, bottles; and metal, not plastic, containers. Developing cognition helps preliterate children distinguish safe from dangerous household products. Multiple aspects of product packaging may reduce child poisoning risk if implemented by industry or policy. © The Author 2014. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Signal transducer and activator of transcription 3 activation is associated with bladder cancer cell growth and survival

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Hsieh Fu-Chuan

2008-10-01

Full Text Available Abstract Background Constitutive activation of signal transducer and activator of transcription 3 (Stat3 signaling pathway plays an important role in several human cancers. Activation of Stat3 is dependent on the phosphorylation at the tyrosine residue 705 by upstream kinases and subsequent nuclear translocation after dimerization. It remains unclear whether oncogenic Stat3 signaling pathway is involved in the oncogenesis of bladder cancer. Results We found that elevated Stat3 phosphorylation in 19 of 100 (19% bladder cancer tissues as well as bladder cancer cell lines, WH, UMUC-3 and 253J. To explore whether Stat3 activation is associated with cell growth and survival of bladder cancer, we targeted the Stat3 signaling pathway in bladder cancer cells using an adenovirus-mediated dominant-negative Stat3 (Y705F and a small molecule compound, STA-21. Both prohibited cell growth and induction of apoptosis in these bladder cancer cell lines but not in normal bladder smooth muscle cell (BdSMC. The survival inhibition might be mediated through apoptotic caspase 3, 8 and 9 pathways. Moreover, down-regulation of anti-apoptotic genes (Bcl-2, Bcl-xL and survivin and a cell cycle regulating gene (cyclin D1 was associated with the cell growth inhibition and apoptosis. Conclusion These results indicated that activation of Stat3 is crucial for bladder cancer cell growth and survival. Therefore, interference of Stat3 signaling pathway emerges as a potential therapeutic approach for bladder cancer.

Single amino acid change in STING leads to constitutive active signaling.

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Eric D Tang

Full Text Available The production of cytokines by the immune system in response to cytosolic DNA plays an important role in host defense, autoimmune disease, and cancer immunogenicity. Recently a cytosolic DNA signaling pathway that is dependent on the endoplasmic reticulum adaptor and cyclic dinucleotide sensor protein STING has been identified. Association of cytosolic DNA with cyclic-GMP-AMP synthase (cGAS activates its enzymatic activity to synthesize the cyclic dinucleotide second messenger cGAMP from GTP and ATP. Direct detection of cGAMP by STING triggers the activation of IRF3 and NF-kB, and the production of type I interferons and proinflammatory cytokines. The mechanism of how STING is able to mediate downstream signaling remains incompletely understood although it has been shown that dimerization is a prerequisite. Here, we identify a single amino acid change in STING that confers constitutive active signaling. This mutation appears to both enhance ability of STING to both dimerize and associate with its downstream target TBK1.

Single amino acid change in STING leads to constitutive active signaling.

Science.gov (United States)

Tang, Eric D; Wang, Cun-Yu

2015-01-01

The production of cytokines by the immune system in response to cytosolic DNA plays an important role in host defense, autoimmune disease, and cancer immunogenicity. Recently a cytosolic DNA signaling pathway that is dependent on the endoplasmic reticulum adaptor and cyclic dinucleotide sensor protein STING has been identified. Association of cytosolic DNA with cyclic-GMP-AMP synthase (cGAS) activates its enzymatic activity to synthesize the cyclic dinucleotide second messenger cGAMP from GTP and ATP. Direct detection of cGAMP by STING triggers the activation of IRF3 and NF-kB, and the production of type I interferons and proinflammatory cytokines. The mechanism of how STING is able to mediate downstream signaling remains incompletely understood although it has been shown that dimerization is a prerequisite. Here, we identify a single amino acid change in STING that confers constitutive active signaling. This mutation appears to both enhance ability of STING to both dimerize and associate with its downstream target TBK1.

Activation of MAPK/ERK signaling by Burkholderia pseudomallei cycle inhibiting factor (Cif.

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Mei Ying Ng

Full Text Available Cycle inhibiting factors (Cifs are virulence proteins secreted by the type III secretion system of some Gram-negative pathogenic bacteria including Burkholderia pseudomallei. Cif is known to function to deamidate Nedd8, leading to inhibition of Cullin E3 ubiquitin ligases (CRL and consequently induction of cell cycle arrest. Here we show that Cif can function as a potent activator of MAPK/ERK signaling without significant activation of other signaling pathways downstream of receptor tyrosine kinases. Importantly, we found that the ability of Cif to activate ERK is dependent on its deamidase activity, but independent of Cullin E3 ligase inhibition. This suggests that apart from Nedd8, other cellular targets of Cif-dependent deamidation exist. We provide evidence that the mechanism involved in Cif-mediated ERK activation is dependent on recruitment of the Grb2-SOS1 complex to the plasma membrane. Further investigation revealed that Cif appears to modify the phosphorylation status of SOS1 in a region containing the CDC25-H and proline-rich domains. It is known that prolonged Cullin E3 ligase inhibition leads to cellular apoptosis. Therefore, we hypothesize that ERK activation is an important mechanism to counter the pro-apoptotic effects of Cif. Indeed, we show that Cif dependent ERK activation promotes phosphorylation of the proapoptotic protein Bim, thereby potentially conferring a pro-survival signal. In summary, we identified a novel deamidation-dependent mechanism of action of the B. pseudomallei virulence factor Cif/CHBP to activate MAPK/ERK signaling. Our study demonstrates that bacterial proteins such as Cif can serve as useful molecular tools to uncover novel aspects of mammalian signaling pathways.

Normalization of voltage-sensitive dye signal with functional activity measures.

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Kentaroh Takagaki

Full Text Available In general, signal amplitude in optical imaging is normalized using the well-established DeltaF/F method, where functional activity is divided by the total fluorescent light flux. This measure is used both directly, as a measure of population activity, and indirectly, to quantify spatial and spatiotemporal activity patterns. Despite its ubiquitous use, the stability and accuracy of this measure has not been validated for voltage-sensitive dye imaging of mammalian neocortex in vivo. In this report, we find that this normalization can introduce dynamic biases. In particular, the DeltaF/F is influenced by dye staining quality, and the ratio is also unstable over the course of experiments. As methods to record and analyze optical imaging signals become more precise, such biases can have an increasingly pernicious impact on the accuracy of findings, especially in the comparison of cytoarchitechtonic areas, in area-of-activation measurements, and in plasticity or developmental experiments. These dynamic biases of the DeltaF/F method may, to an extent, be mitigated by a novel method of normalization, DeltaF/DeltaF(epileptiform. This normalization uses as a reference the measured activity of epileptiform spikes elicited by global disinhibition with bicuculline methiodide. Since this normalization is based on a functional measure, i.e. the signal amplitude of "hypersynchronized" bursts of activity in the cortical network, it is less influenced by staining of non-functional elements. We demonstrate that such a functional measure can better represent the amplitude of population mass action, and discuss alternative functional normalizations based on the amplitude of synchronized spontaneous sleep-like activity. These findings demonstrate that the traditional DeltaF/F normalization of voltage-sensitive dye signals can introduce pernicious inaccuracies in the quantification of neural population activity. They further suggest that normalization

Container for shipping dangerous material

International Nuclear Information System (INIS)

Blum, P.T.

1987-01-01

This container for shipping dangerous material is made by a cylindrical casing of austenitic stainless steel with rounded ends and walls of uniform thickness with welded joins, a tubular metal shock absorber fixed over each end of the casing, removable lugs fixed to the casing, optionally retainers for the material within the casing [fr

The potential predictability of fire danger provided by ECMWF forecast

Science.gov (United States)

Di Giuseppe, Francesca

2017-04-01

The European Forest Fire Information System (EFFIS), is currently being developed in the framework of the Copernicus Emergency Management Services to monitor and forecast fire danger in Europe. The system provides timely information to civil protection authorities in 38 nations across Europe and mostly concentrates on flagging regions which might be at high danger of spontaneous ignition due to persistent drought. The daily predictions of fire danger conditions are based on the US Forest Service National Fire Danger Rating System (NFDRS), the Canadian forest service Fire Weather Index Rating System (FWI) and the Australian McArthur (MARK-5) rating systems. Weather forcings are provided in real time by the European Centre for Medium range Weather Forecasts (ECMWF) forecasting system. The global system's potential predictability is assessed using re-analysis fields as weather forcings. The Global Fire Emissions Database (GFED4) provides 11 years of observed burned areas from satellite measurements and is used as a validation dataset. The fire indices implemented are good predictors to highlight dangerous conditions. High values are correlated with observed fire and low values correspond to non observed events. A more quantitative skill evaluation was performed using the Extremal Dependency Index which is a skill score specifically designed for rare events. It revealed that the three indices were more skilful on a global scale than the random forecast to detect large fires. The performance peaks in the boreal forests, in the Mediterranean, the Amazon rain-forests and southeast Asia. The skill-scores were then aggregated at country level to reveal which nations could potentiallty benefit from the system information in aid of decision making and fire control support. Overall we found that fire danger modelling based on weather forecasts, can provide reasonable predictability over large parts of the global landmass.

Regulation of protease-activated receptor 1 signaling by the adaptor protein complex 2 and R4 subfamily of regulator of G protein signaling proteins.

Science.gov (United States)

Chen, Buxin; Siderovski, David P; Neubig, Richard R; Lawson, Mark A; Trejo, Joann

2014-01-17

The G protein-coupled protease-activated receptor 1 (PAR1) is irreversibly proteolytically activated by thrombin. Hence, the precise regulation of PAR1 signaling is important for proper cellular responses. In addition to desensitization, internalization and lysosomal sorting of activated PAR1 are critical for the termination of signaling. Unlike most G protein-coupled receptors, PAR1 internalization is mediated by the clathrin adaptor protein complex 2 (AP-2) and epsin-1, rather than β-arrestins. However, the function of AP-2 and epsin-1 in the regulation of PAR1 signaling is not known. Here, we report that AP-2, and not epsin-1, regulates activated PAR1-stimulated phosphoinositide hydrolysis via two different mechanisms that involve, in part, a subset of R4 subfamily of "regulator of G protein signaling" (RGS) proteins. A significantly greater increase in activated PAR1 signaling was observed in cells depleted of AP-2 using siRNA or in cells expressing a PAR1 (420)AKKAA(424) mutant with defective AP-2 binding. This effect was attributed to AP-2 modulation of PAR1 surface expression and efficiency of G protein coupling. We further found that ectopic expression of R4 subfamily members RGS2, RGS3, RGS4, and RGS5 reduced activated PAR1 wild-type signaling, whereas signaling by the PAR1 AKKAA mutant was minimally affected. Intriguingly, siRNA-mediated depletion analysis revealed a function for RGS5 in the regulation of signaling by the PAR1 wild type but not the AKKAA mutant. Moreover, activation of the PAR1 wild type, and not the AKKAA mutant, induced Gαq association with RGS3 via an AP-2-dependent mechanism. Thus, AP-2 regulates activated PAR1 signaling by altering receptor surface expression and through recruitment of RGS proteins.

Kurarinol induces hepatocellular carcinoma cell apoptosis through suppressing cellular signal transducer and activator of transcription 3 signaling

International Nuclear Information System (INIS)

Shu, Guangwen; Yang, Jing; Zhao, Wenhao; Xu, Chan; Hong, Zongguo; Mei, Zhinan; Yang, Xinzhou

2014-01-01

Kurarinol is a flavonoid isolated from roots of the medical plant Sophora flavescens. However, its cytotoxic activity against hepatocellular carcinoma (HCC) cells and toxic effects on mammalians remain largely unexplored. Here, the pro-apoptotic activities of kurarinol on HCC cells and its toxic impacts on tumor-bearing mice were evaluated. The molecular mechanisms underlying kurarinol-induced HCC cell apoptosis were also investigated. We found that kurarinol dose-dependently provoked HepG2, Huh-7 and H22 HCC cell apoptosis. In addition, kurarinol gave rise to a considerable decrease in the transcriptional activity of signal transducer and activator of transcription 3 (STAT3) in HCC cells. Suppression of STAT3 signaling is involved in kurarinol-induced HCC cell apoptosis. In vivo studies showed that kurarinol injection substantially induced transplanted H22 cell apoptosis with low toxic impacts on tumor-bearing mice. Similarly, the transcriptional activity of STAT3 in transplanted tumor tissues was significantly suppressed after kurarinol treatment. Collectively, our current research demonstrated that kurarinol has the capacity of inducing HCC cell apoptosis both in vitro and in vivo with undetectable toxic impacts on the host. Suppressing STAT3 signaling is implicated in kurarinol-mediated HCC cell apoptosis. - Highlights: • Kurarinol induces hepatocellular carcinoma (HCC) cell apoptosis. • Kurarinol induces HCC cell apoptosis via inhibiting STAT3. • Kurarinol exhibits low toxic effects on tumor-bearing animals

Caffeine Induces Cell Death via Activation of Apoptotic Signal and Inactivation of Survival Signal in Human Osteoblasts

Directory of Open Access Journals (Sweden)

Wen-Hsiung Chan

2008-05-01

Full Text Available Caffeine consumption is a risk factor for osteoporosis, but the precise regulatory mechanisms are currently unknown. Here, we show that cell viability decreases in osteoblasts treated with caffeine in a dose-dependent manner. This cell death is attributed primarily to apoptosis and to a smaller extent, necrosis. Moreover, caffeine directly stimulates intracellular oxidative stress. Our data support caffeine-induced apoptosis in osteoblasts via a mitochondria-dependent pathway. The apoptotic biochemical changes were effectively prevented upon pretreatment with ROS scavengers, indicating that ROS plays a critical role as an upstream controller in the caffeine-induced apoptotic cascade. Additionally, p21-activated protein kinase 2 (PAK2 and c-Jun N-terminal kinase (JNK were activated in caffeine-treated osteoblasts. Experiments further found that PAK2 activity is required for caffeine-induced JNK activation and apoptosis. Importantly, our data also show that caffeine triggers cell death via inactivation of the survival signal, including the ERK- and Akt-mediated anti-apoptotic pathways. Finally, exposure of rats to dietary water containing 10~20 μM caffeine led to bone mineral density loss. These results demonstrate for the first time that caffeine triggers apoptosis in osteoblasts via activation of mitochondria-dependent cell death signaling and inactivation of the survival signal, and causes bone mineral density loss in vivo.

Grout Treatment Facility dangerous waste permit application

International Nuclear Information System (INIS)

1992-07-01

The Grout Treatment Facility (GTF) is an existing treatment, storage, and/or disposal (TSD) unit located in the 200 East Area and the adjacent 600 Area of the Hanford Site. The GTF mixes dry cementitious solids with liquid mixed waste (containing both dangerous and radioactive constituents) produced by Hanford Site operations. The GTF consists of the following: The 241-AP-02D and 241-AP-04D waste pump pits and transfer piping; Dry Materials Facility (DMF); Grout Disposal Facility (GDF), consisting of the disposal vault and support and monitoring equipment; and Grout Processing Facility (GPF) and Westinghouse Hanford Company on the draft Hanford Facility Dangerous Waste Permit and may not be read to conflict with those comments. The Grout Treatment Facility Dangerous Waste Permit Application consists of both a Part A and a Part B permit application. An explanation of the Part A revisions associated with this TSD unit, including the current revision, is provided at the beginning of the Part A section. The Part B consists of 15 chapters addressing the organization and content of the Part B checklist prepared by the Washington State Department of Ecology (Ecology 1987). For ease of reference, the checklist section numbers, in brackets, follow chapter headings and subheadings

Receptor activity-independent recruitment of βarrestin2 reveals specific signalling modes

Science.gov (United States)

Terrillon, Sonia; Bouvier, Michel

2004-01-01

The roles of βarrestins in regulating G protein coupling and receptor endocytosis following agonist stimulation of G protein-coupled receptors are well characterised. However, their ability to act on their own as direct modulators or activators of signalling remains poorly characterised. Here, βarrestin2 intrinsic signalling properties were assessed by forcing the recruitment of this accessory protein to vasopressin V1a or V2 receptors independently of agonist-promoted activation of the receptors. Such induction of a stable interaction with βarrestin2 initiated receptor endocytosis leading to intracellular accumulation of the βarrestin/receptor complexes. Interestingly, βarrestin2 association to a single receptor protomer was sufficient to elicit receptor dimer internalisation. In addition to recapitulating βarrestin2 classical actions on receptor trafficking, the receptor activity-independent recruitment of βarrestin2 activated the extracellular signal-regulated kinases. In the latter case, recruitment to the receptor itself was not required since kinase activation could be mediated by βarrestin2 translocation to the plasma membrane in the absence of any interacting receptor. These data demonstrate that βarrestin2 can act as a ‘bonafide' signalling molecule even in the absence of activated receptor. PMID:15385966

The detection of cavitation in hydraulic machines by use of ultrasonic signal analysis

International Nuclear Information System (INIS)

Gruber, P; Odermatt, P; Etterlin, M; Lerch, T; Frei, M; Farhat, M

2014-01-01

This presentation describes an experimental approach for the detection of cavitation in hydraulic machines by use of ultrasonic signal analysis. Instead of using the high frequency pulses (typically 1MHz) only for transit time measurement different other signal characteristics are extracted from the individual signals and its correlation function with reference signals in order to gain knowledge of the water conditions. As the pulse repetition rate is high (typically 100Hz), statistical parameters can be extracted of the signals. The idea is to find patterns in the parameters by a classifier that can distinguish between the different water states. This classification scheme has been applied to different cavitation sections: a sphere in a water flow in circular tube at the HSLU in Lucerne, a NACA profile in a cavitation tunnel and a Francis model test turbine both at LMH in Lausanne. From the signal raw data several statistical parameters in the time and frequency domain as well as from the correlation function with reference signals have been determined. As classifiers two methods were used: neural feed forward networks and decision trees. For both classification methods realizations with lowest complexity as possible are of special interest. It is shown that three signal characteristics, two from the signal itself and one from the correlation function are in many cases sufficient for the detection capability. The final goal is to combine these results with operating point, vibration, acoustic emission and dynamic pressure information such that a distinction between dangerous and not dangerous cavitation is possible

Double-shell tank system dangerous waste permit application

International Nuclear Information System (INIS)

1991-06-01

This Double-Shell Tank System Dangerous Waste Permit Application should be read in conjunction with the 242-A Evaporator Dangerous Waste Permit Application and the Liquid Effluent Retention Facility Dangerous Waste Permit Application, also submitted on June 28, 1991. Information contained in the Double-Shell Tank System permit application is referenced in the other two permit applications. The Double-Shell Tank System stores and treats mixed waste received from a variety of sources on the Hanford Site. The 242-A Evaporator treats liquid mixed waste received from the double-shell tanks. The 242-A Evaporator returns a mixed-waste slurry to the double-shell tanks and generates the dilute mixed-waste stream stored in the Liquid Effluent Retention Facility. This report contains information on the following topics: Facility Description and General Provisions; Waste Characteristics; Process Information; Groundwater Monitoring; Procedures to Prevent Hazards; Contingency Plan; Personnel Training; Exposure Information Report; Waste Minimization Plan; Closure and Postclosure Requirements; Reporting and Recordkeeping; other Relevant Laws; and Certification. 150 refs., 141 figs., 118 tabs

The state control of radioecological danger of the sunken and scuttled nuclear objects on the sea bottom in Russian Federation

International Nuclear Information System (INIS)

Lisovsky, I.V.

2000-01-01

register of underwater potentially dangerous objects. The purpose of a commission is coordination of work on a problem and development of the federal program of perspective work. On the basis of the register development of the Federal Program for the warning and liquidation of extreme situations with underwater potentially dangerous objects of Russian Federation is supposed. Necessity of creation and association of special forces and means for realization of measures on prevention of threat and liquidation of consequences of failures, connected with underwater potentially dangerous objects is certain. It is necessary to emphasize, that within the framework of the federal program of work of the Russian participants on the given problem the international projects of various scale can be offered, switching on especially research and regional, connected with investment activity, supposing international examination of the safety of the perspective projects and technologies. (author)

33 CFR 95.020 - Standard for under the influence of alcohol or a dangerous drug.

Science.gov (United States)

2010-07-01

... of alcohol or a dangerous drug. 95.020 Section 95.020 Navigation and Navigable Waters COAST GUARD... ALCOHOL OR A DANGEROUS DRUG § 95.020 Standard for under the influence of alcohol or a dangerous drug. An individual is under the influence of alcohol or a dangerous drug when: (a) The individual is operating a...

33 CFR 95.030 - Evidence of under the influence of alcohol or a dangerous drug.

Science.gov (United States)

2010-07-01

... of alcohol or a dangerous drug. 95.030 Section 95.030 Navigation and Navigable Waters COAST GUARD... ALCOHOL OR A DANGEROUS DRUG § 95.030 Evidence of under the influence of alcohol or a dangerous drug. Acceptable evidence of when a vessel operator is under the influence of alcohol or a dangerous drug includes...

Nandrolone reduces activation of Notch signaling in denervated muscle associated with increased Numb expression

International Nuclear Information System (INIS)

Liu, Xin-Hua; Yao, Shen; Qiao, Rui-Fang; Levine, Alice C.; Kirschenbaum, Alexander; Pan, Jiangping; Wu, Yong; Qin, Weiping; Bauman, William A.; Cardozo, Christopher P.

2011-01-01

Highlights: → Nerve transection increased Notch signaling in paralyzed muscle. → Nandrolone prevented denervation-induced Notch signaling. → Nandrolone induced the expression of an inhibitor of the Notch signaling, Numb. → Reduction of denervation-induced Notch signaling by nandrolone is likely through upregulation of Numb. -- Abstract: Nandrolone, an anabolic steroid, slows denervation-atrophy in rat muscle. The molecular mechanisms responsible for this effect are not well understood. Androgens and anabolic steroids activate Notch signaling in animal models of aging and thereby mitigate sarcopenia. To explore the molecular mechanisms by which nandrolone prevents denervation-atrophy, we investigated the effects of nandrolone on Notch signaling in denervated rat gastrocnemius muscle. Denervation significantly increased Notch activity reflected by elevated levels of nuclear Notch intracellular domain (NICD) and expression of Hey1 (a Notch target gene). Activation was greatest at 7 and 35 days after denervation but remained present at 56 days after denervation. Activation of Notch in denervated muscle was prevented by nandrolone associated with upregulated expression of Numb mRNA and protein. These data demonstrate that denervation activates Notch signaling, and that nandrolone abrogates this response associated with increased expression of Numb, suggesting a potential mechanism by which nandrolone reduces denervation-atrophy.

Nandrolone reduces activation of Notch signaling in denervated muscle associated with increased Numb expression

Energy Technology Data Exchange (ETDEWEB)

Liu, Xin-Hua [Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peter VA Medical Center, Bronx, NY 10468 (United States); Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029 (United States); Yao, Shen; Qiao, Rui-Fang; Levine, Alice C. [Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029 (United States); Kirschenbaum, Alexander [Department of Urology, Mount Sinai School of Medicine, New York, NY 10029 (United States); Pan, Jiangping; Wu, Yong [Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peter VA Medical Center, Bronx, NY 10468 (United States); Qin, Weiping [Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peter VA Medical Center, Bronx, NY 10468 (United States); Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029 (United States); Bauman, William A. [Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peter VA Medical Center, Bronx, NY 10468 (United States); Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029 (United States); Rehabilitation Medicine, Mount Sinai School of Medicine, New York, NY 10029 (United States); Cardozo, Christopher P., E-mail: chris.cardozo@mssm.edu [Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peter VA Medical Center, Bronx, NY 10468 (United States); Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029 (United States); Rehabilitation Medicine, Mount Sinai School of Medicine, New York, NY 10029 (United States)

2011-10-14

Highlights: {yields} Nerve transection increased Notch signaling in paralyzed muscle. {yields} Nandrolone prevented denervation-induced Notch signaling. {yields} Nandrolone induced the expression of an inhibitor of the Notch signaling, Numb. {yields} Reduction of denervation-induced Notch signaling by nandrolone is likely through upregulation of Numb. -- Abstract: Nandrolone, an anabolic steroid, slows denervation-atrophy in rat muscle. The molecular mechanisms responsible for this effect are not well understood. Androgens and anabolic steroids activate Notch signaling in animal models of aging and thereby mitigate sarcopenia. To explore the molecular mechanisms by which nandrolone prevents denervation-atrophy, we investigated the effects of nandrolone on Notch signaling in denervated rat gastrocnemius muscle. Denervation significantly increased Notch activity reflected by elevated levels of nuclear Notch intracellular domain (NICD) and expression of Hey1 (a Notch target gene). Activation was greatest at 7 and 35 days after denervation but remained present at 56 days after denervation. Activation of Notch in denervated muscle was prevented by nandrolone associated with upregulated expression of Numb mRNA and protein. These data demonstrate that denervation activates Notch signaling, and that nandrolone abrogates this response associated with increased expression of Numb, suggesting a potential mechanism by which nandrolone reduces denervation-atrophy.

77 FR 17569 - United States-Canada Regulatory Cooperation Council (RCC)-Transportation-Dangerous Goods Working...

Science.gov (United States)

2012-03-26

... identified in the Joint Action Plan, the Transportation--Dangerous Goods Working Group led by senior...)-- Transportation--Dangerous Goods Working Group AGENCY: Pipeline and Hazardous Materials Safety Administration...--Dangerous Goods Working Group, of the United States-Canada Regulatory Cooperation Council (RCC). Comments...

Activation of Symbiosis Signaling by Arbuscular Mycorrhizal Fungi in Legumes and Rice[OPEN

Science.gov (United States)

Sun, Jongho; Miller, J. Benjamin; Granqvist, Emma; Wiley-Kalil, Audrey; Gobbato, Enrico; Maillet, Fabienne; Cottaz, Sylvain; Samain, Eric; Venkateshwaran, Muthusubramanian; Fort, Sébastien; Morris, Richard J.; Ané, Jean-Michel; Dénarié, Jean; Oldroyd, Giles E.D.

2015-01-01

Establishment of arbuscular mycorrhizal interactions involves plant recognition of diffusible signals from the fungus, including lipochitooligosaccharides (LCOs) and chitooligosaccharides (COs). Nitrogen-fixing rhizobial bacteria that associate with leguminous plants also signal to their hosts via LCOs, the so-called Nod factors. Here, we have assessed the induction of symbiotic signaling by the arbuscular mycorrhizal (Myc) fungal-produced LCOs and COs in legumes and rice (Oryza sativa). We show that Myc-LCOs and tetra-acetyl chitotetraose (CO4) activate the common symbiosis signaling pathway, with resultant calcium oscillations in root epidermal cells of Medicago truncatula and Lotus japonicus. The nature of the calcium oscillations is similar for LCOs produced by rhizobial bacteria and by mycorrhizal fungi; however, Myc-LCOs activate distinct gene expression. Calcium oscillations were activated in rice atrichoblasts by CO4, but not the Myc-LCOs, whereas a mix of CO4 and Myc-LCOs activated calcium oscillations in rice trichoblasts. In contrast, stimulation of lateral root emergence occurred following treatment with Myc-LCOs, but not CO4, in M. truncatula, whereas both Myc-LCOs and CO4 were active in rice. Our work indicates that legumes and non-legumes differ in their perception of Myc-LCO and CO signals, suggesting that different plant species respond to different components in the mix of signals produced by arbuscular mycorrhizal fungi. PMID:25724637

Activation of Extracellular Signal-Regulated Kinase but Not of p38 Mitogen-Activated Protein Kinase Pathways in Lymphocytes Requires Allosteric Activation of SOS

Science.gov (United States)

Jun, Jesse E.; Yang, Ming; Chen, Hang; Chakraborty, Arup K.

2013-01-01

Thymocytes convert graded T cell receptor (TCR) signals into positive selection or deletion, and activation of extracellular signal-related kinase (ERK), p38, and Jun N-terminal protein kinase (JNK) mitogen-activated protein kinases (MAPKs) has been postulated to play a discriminatory role. Two families of Ras guanine nucleotide exchange factors (RasGEFs), SOS and RasGRP, activate Ras and the downstream RAF-MEK-ERK pathway. The pathways leading to lymphocyte p38 and JNK activation are less well defined. We previously described how RasGRP alone induces analog Ras-ERK activation while SOS and RasGRP cooperate to establish bimodal ERK activation. Here we employed computational modeling and biochemical experiments with model cell lines and thymocytes to show that TCR-induced ERK activation grows exponentially in thymocytes and that a W729E allosteric pocket mutant, SOS1, can only reconstitute analog ERK signaling. In agreement with RasGRP allosterically priming SOS, exponential ERK activation is severely decreased by pharmacological or genetic perturbation of the phospholipase Cγ (PLCγ)-diacylglycerol-RasGRP1 pathway. In contrast, p38 activation is not sharply thresholded and requires high-level TCR signal input. Rac and p38 activation depends on SOS1 expression but not allosteric activation. Based on computational predictions and experiments exploring whether SOS functions as a RacGEF or adaptor in Rac-p38 activation, we established that the presence of SOS1, but not its enzymatic activity, is critical for p38 activation. PMID:23589333

A dangerous movie? Hollywood does psychoanalysis.

Science.gov (United States)

Ferrell, Donald R; Silverman, Martin A

2014-12-01

After the appearance of David Cronenberg's film A Dangerous Method in 2011, dealing with the relationships of Sigmund Freud, C. G. Jung and Sabina Spielrein, Dr. Donald Ferrell published: A Dangerous Method, A Film Directed by David Cronenberg: An Extended Review (Ferrell 2012) in the Journal of Religion and Health. Upon its publication, Dr. Ferrell's article was nominated for a Gradiva Award by the National Association for the Advancement of Psychoanalysis. On November 1, 2013, the Association for the Psychoanalysis of Culture and Society held its annual conference at Rutgers University, New Brunswick, NJ. Dr. Billie Pivnick, a member at large of the Board of Directors of the APCS and also on the Editorial Board of the Journal of Religion and Health, persuaded the 2013 Conference Program Committee that Cronenberg's film would make an interesting subject for discussion for conference participants. To that end, Dr. Pivnick invited Dr. Ferrell, C. G. Jung Institute of New York, Dr. Steven Reisner, Coalition for an Ethical Psychology, and Dr. Martin Silverman, Training and Supervising Analyst and Supervising Child Analyst at the Institute for Psychoanalytic Education, NYU College of Medicine, Training and Supervising Analyst at the Center for Psychotherapy and Psychoanalysis of New Jersey, and Associate Editor of The Psychoanalytic Quarterly to serve as panel members to discuss: A Dangerous Movie? Hollywood does Psychoanalysis. Presentations on Cronenberg's film and the early history of psychoanalysis were given by Drs. Ferrell and Reisner, followed by a response to their presentations by Dr. Silverman. Dr. Pivnick chaired the session. The articles presented here were given originally at the APCS conference by Dr. Ferrell and Dr. Silverman. Dr. Reisner declined the invitation to submit his presentation for publication. Dr. Silverman's remarks were based not only on the presentation given by Dr. Ferrell at the session on A Dangerous Movie?, but also on his close and

[Accidents on Iceland's most dangerous roads].

Science.gov (United States)

Bjarnason, Thóroddur; Arnarsson, Sveinn

2012-02-01

The objective of this paper was to identify the most dangerous segments of the Icelandic road system in terms of the number of accidents pr km and the rate of accidents pr million km travelled. First to identify the segments where the number of accidents is highest and where the risk of the individual traveller is the greatest. Second to evaluate if the association between the number and the rate of accidents is positive or negative. Third to identify the road segments that are the most dangerous in the sense of many accidents and great risk to individual travellers. Main roads outside urban centers were divided into 45 segments that were on average 78 km in length. Infrequently travelled roads and roads within urban centers were omitted. Information on the length of roads, traffic density and number of accidents was used to calculate the number of accidents per km and the rate of accidents per million km travelled. The correlation between the number and rate of accidents was calculated and the most dangerous road segments were identified by the average rank order on both dimensions. Most accidents pr km occurred on the main roads to and from the capital region, but also east towards Hvolsvöllur, north towards Akureyri and in the Mideast region of the country. The rate of accidents pr million km travelled was highest in the northeast region, in northern Snæfellsnes and in the Westfjords. The most dangerous roads on both dimensions were in Mideast, northern Westfjords, in the north between Blönduós and Akureyri and in northern Snæfellsnes. Most accidents pr km occurred on roads with a low accident rate pr million km travelled. It is therefore possible to reduce accidents the most by increasing road safety where it is already the greatest but that would however increase inequalities in road safety. Policy development in transportation is therefore in part a question of priorities in healthcare. Individual equality in safety and health are not always fully

Telomerase activity promotes osteoblast differentiation by modulating IGF-signaling pathway

DEFF Research Database (Denmark)

Saeed, Hamid; Qiu, Weimin; Li, Chen

2015-01-01

-regulation of several components of insulin-like growth factor (IGF) signaling. Specifically, a significant increase in IGF-induced AKT phosphorylation and alkaline phosphatase (ALP) activity were observed in hMSC-TERT. Enhanced ALP activity was reduced in presence of IGF1 receptor inhibitor: picropodophyllin....... In addition, telomerase deficiency caused significant reduction in IGF signaling proteins in osteoblastic cells cultured from telomerase deficient mice (Terc (-/-)). The low bone mass exhibited by Terc (-/-) mice was associated with significant reduction in serum levels of IGF1 and IGFBP3 as well as reduced...... skeletal mRNA expression of Igf1, Igf2, Igf2r, Igfbp5 and Igfbp6. IGF1-induced osteoblast differentiation was also impaired in Terc (-/-) MSC. In conclusion, our data demonstrate that impaired IGF/AKT signaling contributes to the observed decreased bone mass and bone formation exhibited by telomerase...

Adipocyte activation of cancer stem cell signaling in breast cancer

Institute of Scientific and Technical Information of China (English)

Benjamin; Wolfson; Gabriel; Eades; Qun; Zhou

2015-01-01

Signaling within the tumor microenvironment has a critical role in cancer initiation and progression. Adipocytes, one of the major components of the breast microenvironment,have been shown to provide pro-tumorigenic signals that promote cancer cell proliferation and invasiveness in vitro and tumorigenicity in vivo. Adipocyte secreted factors such as leptin and interleukin-6(IL-6) have a paracrine effect on breast cancer cells. In adipocyte-adjacent breast cancer cells, the leptin and IL-6 signaling pathways activate janus kinase 2/signal transducer and activatorof transcription 5, promoting the epithelial-mesenchymal transition, and upregulating stemness regulators such as Notch, Wnt and the Sex determining region Y-box 2/octamer binding transcription factor 4/Nanog signaling axis. In this review we will summarize the major signaling pathways that regulate cancer stem cells in breast cancer and describe the effects that adipocyte secreted IL-6 and leptin have on breast cancer stem cell signaling. Finally we will introduce a new potential treatment paradigm of inhibiting the adipocyte-breast cancer cell signaling via targeting the IL-6 or leptin pathways.

Activation of Toll-like receptors nucleates assembly of the MyDDosome signaling hub.

Science.gov (United States)

Latty, Sarah Louise; Sakai, Jiro; Hopkins, Lee; Verstak, Brett; Paramo, Teresa; Berglund, Nils A; Cammorota, Eugenia; Cicuta, Pietro; Gay, Nicholas J; Bond, Peter J; Klenerman, David; Bryant, Clare E

2018-01-24

Infection and tissue damage induces assembly of supramolecular organizing centres (SMOCs)), such as the Toll-like receptor (TLR) MyDDosome, to co-ordinate inflammatory signaling. SMOC assembly is thought to drive digital all-or-none responses, yet TLR activation by diverse microbes induces anything from mild to severe inflammation. Using single-molecule imaging of TLR4-MyDDosome signaling in living macrophages, we find that MyDDosomes assemble within minutes of TLR4 stimulation. TLR4/MD2 activation leads only to formation of TLR4/MD2 heterotetramers, but not oligomers, suggesting a stoichiometric mismatch between activated receptors and MyDDosomes. The strength of TLR4 signalling depends not only on the number and size of MyDDosomes formed but also how quickly these structures assemble. Activated TLR4, therefore, acts transiently nucleating assembly of MyDDosomes, a process that is uncoupled from receptor activation. These data explain how the oncogenic mutation of MyD88 (L265P) assembles MyDDosomes in the absence of receptor activation to cause constitutive activation of pro-survival NF-κB signalling. © 2018, Latty et al.

Neighborhood Danger, Parental Monitoring, Harsh Parenting, and Child Aggression in Nine Countries

Directory of Open Access Journals (Sweden)

Ann T. Skinner

2014-01-01

Full Text Available Exposure to neighborhood danger during childhood has negative effects that permeate multiple dimensions of childhood. The current study examined whether mothers’, fathers’, and children’s perceptions of neighborhood danger are related to child aggression, whether parental monitoring moderates this relation, and whether harsh parenting mediates this relation. Interviews were conducted with a sample of 1293 children (age M = 10.68, SD = 0.66; 51% girls and their mothers (n = 1282 and fathers (n = 1075 in nine countries (China, Colombia, Italy, Jordan, Kenya, the Philippines, Sweden, Thailand, and the United States. Perceptions of greater neighborhood danger were associated with more child aggression in all nine countries according to mothers’ and fathers’ reports and in five of the nine countries according to children’s reports. Parental monitoring did not moderate the relation between perception of neighborhood danger and child aggression. The mediating role of harsh parenting was inconsistent across countries and reporters. Implications for further research are discussed, and include examination of more specific aspects of parental monitoring as well as more objective measures of neighborhood danger.

Legislation on carriage of dangerous goods. Acts - directives - exemptions. 2. rev. ed.

International Nuclear Information System (INIS)

Vogt, H.W.

1993-01-01

This compact paperback edition presents the essential chapters of volume 3 'Acts, directives, exemptions' of the publication ''A handbook for dangerous goods officers''. Contents: (1) Act on the Carriage of Dangerous Goods. (2) Ordinance concerning Dangerous Goods Officers (GbV). (3) Legislative intent pursued with the GbV. (4) Instructions for implementation of the GbV. (5) Ordinance on Road Transport of Dangerous Goods (GGVS). (6) Annex A and B of the GGVS. The updating and amendment of the ADR provisions for harmonisation with the international classification schemes and hence the complete revision of categories 4.1, 4.2, 4.3, 5.1, 5.2, and 9, as well as the harmonisation of GGVS provisions with ADR provisions fall both under the 4th Amending Ordinance. This 4th Ordinance Amending the GGVS, passed by the Bundesrat on March 5, 1993 and announced on April 23, 1993, is, of course, part of this edition. Professional subscribers to the publication will prefer the loose-leaf edition of the Handbook for Dangerous Goods Officers, for easy updating of their reference source. (orig./HP) [de

Neighborhood Danger, Parental Monitoring, Harsh Parenting, and Child Aggression in Nine Countries.

Science.gov (United States)

Skinner, Ann T; Bacchini, Dario; Lansford, Jennifer E; Godwin, Jennifer; Sorbring, Emma; Tapanya, Sombat; Tirado, Liliana Maria Uribe; Zelli, Arnaldo; Alampay, Liane Peña; Al-Hassan, Suha M; Bombi, Anna Silvia; Bornstein, Marc H; Chang, Lei; Deater-Deckard, Kirby; Giunta, Laura Di; Dodge, Kenneth A; Malone, Patrick S; Miranda, Maria Concetta; Oburu, Paul; Pastorelli, Concetta

2014-01-20

Exposure to neighborhood danger during childhood has negative effects that permeate multiple dimensions of childhood. The current study examined whether mothers', fathers', and children's perceptions of neighborhood danger are related to child aggression, whether parental monitoring moderates this relation, and whether harsh parenting mediates this relation. Interviews were conducted with a sample of 1,293 children (age M = 10.68, SD = .66; 51% girls) and their mothers ( n = 1,282) and fathers ( n = 1,075) in nine countries (China, Colombia, Italy, Jordan, Kenya, the Philippines, Sweden, Thailand, and the United States). Perceptions of greater neighborhood danger were associated with more child aggression in all nine countries according to mothers' and fathers' reports and in five of the nine countries according to children's reports. Parental monitoring did not moderate the relation between perception of neighborhood danger and child aggression. The mediating role of harsh parenting was inconsistent across countries and reporters. Implications for further research are discussed, and include examination of more specific aspects of parental monitoring as well as more objective measures of neighborhood danger.

Relationship Between Psychological Characteristics Mental Health, Aggression and Driving Habits in Dangerous Drivers

Directory of Open Access Journals (Sweden)

M Mohammadpoor

2010-09-01

Full Text Available Introduction: Today, all kinds of people need vehicles for performing their daily activities. The need for use of these vehicles for transportation frequently leads to a high rate of road accidents and it seems that certain people do not have enough ability to use these vehicles. Dangerous behaviors lead to financial and life risking irreparable damages. Methods: The aim of the study was to examine the relationship between psychological characteristics (mental health, aggression, type A characteristic and driving habits. The researchers chose 110 injured men drivers and asked them to complete the Manchester Driving Behavior, Type A Characteristic, Ahvaz Aggressive and Mental Health questionnaires. The data was analyzed by Pearson's Correlation and Regression Analysis. Results: The findings showed that there is a significant relation between psychological characteristics (mental health, aggression, type A characteristic and driving habits. The regression analysis also foresees the aggressive and mental health of testers’ dangerous driving behavior. Meanwhile, Type A characteristic is not able to foresee driving behaviors. Conclusion: Risky driving is a phenomenon that leads to many irreparable damages for the society and individual. Present study suggests that in order to reduce dangers and probable damages, procurement of driving license procedures should be prolonged and drivers should be regularly assessed psychologically (personal or public. Risky drivers or the attackers who need education or consultation should attend education-consultation programs.

Epigenetic Activation of Wnt/β-Catenin Signaling in NAFLD-Associated Hepatocarcinogenesis

Directory of Open Access Journals (Sweden)

Yuan Tian

2016-08-01

Full Text Available Non-alcoholic fatty liver disease (NAFLD, characterized by fat accumulation in liver, is closely associated with central obesity, over-nutrition and other features of metabolic syndrome, which elevate the risk of developing hepatocellular carcinoma (HCC. The Wnt/β-catenin signaling pathway plays a significant role in the physiology and pathology of liver. Up to half of HCC patients have activation of Wnt/β-catenin signaling. However, the mutation frequencies of CTNNB1 (encoding β-catenin protein or other antagonists targeting Wnt/β-catenin signaling are low in HCC patients, suggesting that genetic mutations are not the major factor driving abnormal β-catenin activities in HCC. Emerging evidence has demonstrated that obesity-induced metabolic pathways can deregulate chromatin modifiers such as histone deacetylase 8 to trigger undesired global epigenetic changes, thereby modifying gene expression program which contributes to oncogenic signaling. This review focuses on the aberrant epigenetic activation of Wnt/β-catenin in the development of NAFLD-associated HCC. A deeper understanding of the molecular mechanisms underlying such deregulation may shed light on the identification of novel druggable epigenetic targets for the prevention and/or treatment of HCC in obese and diabetic patients.

The Drosophila Arf GEF Steppke controls MAPK activation in EGFR signaling.

Science.gov (United States)

Hahn, Ines; Fuss, Bernhard; Peters, Annika; Werner, Tamara; Sieberg, Andrea; Gosejacob, Dominic; Hoch, Michael

2013-06-01

Guanine nucleotide exchange factors (GEFs) of the cytohesin protein family are regulators of GDP/GTP exchange for members of the ADP ribosylation factor (Arf) of small GTPases. They have been identified as modulators of various receptor tyrosine kinase signaling pathways including the insulin, the vascular epidermal growth factor (VEGF) and the epidermal growth factor (EGF) pathways. These pathways control many cellular functions, including cell proliferation and differentiation, and their misregulation is often associated with cancerogenesis. In vivo studies on cytohesins using genetic loss of function alleles are lacking, however, since knockout mouse models are not available yet. We have recently identified mutants for the single cytohesin Steppke (Step) in Drosophila and we could demonstrate an essential role of Step in the insulin signaling cascade. In the present study, we provide in vivo evidence for a role of Step in EGFR signaling during wing and eye development. By analyzing step mutants, transgenic RNA interference (RNAi) and overexpression lines for tissue specific as well as clonal analysis, we found that Step acts downstream of the EGFR and is required for the activation of mitogen-activated protein kinase (MAPK) and the induction of EGFR target genes. We further demonstrate that step transcription is induced by EGFR signaling whereas it is negatively regulated by insulin signaling. Furthermore, genetic studies and biochemical analysis show that Step interacts with the Connector Enhancer of KSR (CNK). We propose that Step may be part of a larger signaling scaffold coordinating receptor tyrosine kinase-dependent MAPK activation.

Tofacitinib Represses the Janus Kinase-Signal Transducer and Activators of Transcription Signalling Pathway in Keratinocytes.

Science.gov (United States)

Srivastava, Ankit; Ståhle, Mona; Pivarcsi, Andor; Sonkoly, Enikö

2018-05-08

Tofacitinib is a Janus kinase (JAK) inhibitor, which has shown efficacy in treating psoriasis. The mode of action of tofacitinib is not completely understood but it has been thought to be mediated by the inhibition of CD4+ T-cell activation. Here, we investigated whether the molecular targets of tofacitinib are expressed in keratinocytes, and whether tofacitinib can modulate the activity of the JAK/Signal Transducer and Activators of Transcription (STAT)-pathway in keratinocytes. Transcriptomic profiling of human keratinocytes treated with IL-22 in combination with tofacitinib revealed that tofacitinib could prevent the majority of IL-22-mediated gene expression changes. Pathway analysis of tofacitinib-regulated genes in keratinocytes revealed enrichment of genes involved in the JAK/STAT signalling pathway. Quantitative real-time-PCR confirmed the upregulation of S100A7 and downregulation of EGR1 expression by IL-22, which was prevented by tofacitinib pre-treatment. These results indicate a direct effect of tofacinitib on keratinocytes, which can have relevance for systemic as well as for topical treatment of psoriasis with tofacitinib.

A fire danger rating system for Hawaii

Science.gov (United States)

Robert E. Burgan; Francis M. Fujioka; George H. Hirata

1974-01-01

Extremes in rainfall on the Hawaiian Islands make it difficult to judge forest fire danger conditions. The use of an automatic data collection and computer processing system helps to monitor the problem.

Modeling DNA?damage-induced pneumopathy in mice: insight from danger signaling cascades

OpenAIRE

Wirsd?rfer, Florian; Jendrossek, Verena

2017-01-01

Radiation-induced pneumonitis and fibrosis represent severe and dose-limiting side effects in the radiotherapy of thorax-associated neoplasms leading to decreased quality of life or - as a consequence of treatment with suboptimal radiation doses - to fatal outcomes by local recurrence or metastatic disease. It is assumed that the initial radiation-induced damage to the resident cells triggers a multifaceted damage-signalling cascade in irradiated normal tissues including a multifactorial secr...

Survey of activated FLT3 signaling in leukemia.

Directory of Open Access Journals (Sweden)

Ting-lei Gu

Full Text Available Activating mutations of FMS-like tyrosine kinase-3 (FLT3 are found in approximately 30% of patients with acute myeloid leukemia (AML. FLT3 is therefore an attractive drug target. However, the molecular mechanisms by which FLT3 mutations lead to cell transformation in AML remain unclear. To develop a better understanding of FLT3 signaling as well as its downstream effectors, we performed detailed phosphoproteomic analysis of FLT3 signaling in human leukemia cells. We identified over 1000 tyrosine phosphorylation sites from about 750 proteins in both AML (wild type and mutant FLT3 and B cell acute lymphoblastic leukemia (normal and amplification of FLT3 cell lines. Furthermore, using stable isotope labeling by amino acids in cell culture (SILAC, we were able to quantified over 400 phosphorylation sites (pTyr, pSer, and pThr that were responsive to FLT3 inhibition in FLT3 driven human leukemia cell lines. We also extended this phosphoproteomic analysis on bone marrow from primary AML patient samples, and identify over 200 tyrosine and 800 serine/threonine phosphorylation sites in vivo. This study showed that oncogenic FLT3 regulates proteins involving diverse cellular processes and affects multiple signaling pathways in human leukemia that we previously appreciated, such as Fc epsilon RI-mediated signaling, BCR, and CD40 signaling pathways. It provides a valuable resource for investigation of oncogenic FLT3 signaling in human leukemia.

Role of signaling lymphocytic activation molecule in T helper cell responses

Directory of Open Access Journals (Sweden)

Jan E. de Vries

1998-01-01

Full Text Available Signaling lymphocytic activation molecule (SLAM; CDw150 is a 70 kDa glycoprotein. Signaling lymphocytic activation molecule is constitutively expressed on memory T cells, CD56+ T cells, a subset of T cell receptor γδ+ cells, immature thymocytes and, at low levels, on a proportion of peripheral blood B cells. Signaling lymphocytic activation molecule is rapidly upregulated on all T and B cells after activation. Engagement of SLAM by F(ab’2 fragments of an anti-SLAM monoclonal antibody (mAb A12 enhances antigen-specific T cell proliferation. In addition, mAb A12 was directly mitogenic for T cell clones and activated T cells. T cell proliferation induced by mAb A12 is independent of interleukin (IL-2, IL-4, IL-12 and IL-15, but is cyclosporin A sensitive. Ligation of SLAM during antigen-specific T cell proliferation resulted in upregulation of interferon (IFN-γ production, even by allergen-specific T helper cell (Th 2 clones, whereas the levels of IL-4 and IL-5 production were only marginally affected. The mAb A12 was unable to induce IL-4 and IL-5 production by Th1 clones. Co-stimulation of skin-derived Der P1-specific Th2 cells from patients with atopic dermatitis via SLAM resulted in the generation of a population of IFN-γ-producing cells, thereby reverting their phenotype to a Th0 pattern. Signaling lymphocytic activation molecule is a high-affinity self ligand mediating homophilic cell interaction. In addition, soluble SLAM enhances both T and B cell proliferation. Collectively, these data indicate that SLAM molecules act both as receptors and ligands that are not only involved in T cell expansion but also drive the expanding T cells during immune responses into the Th0/Th1 pathway. This suggests that signaling through SLAM plays a role in directing Th0/Th1 development.

Cross-sectional survey of knowledge of obstetric danger signs among women in rural Madagascar.

Science.gov (United States)

Salem, Ania; Lacour, Oriane; Scaringella, Stefano; Herinianasolo, Josea; Benski, Anne Caroline; Stancanelli, Giovanna; Vassilakos, Pierre; Petignat, Patrick; Schmidt, Nicole Christine

2018-02-05

Antenatal care (ANC) has the potential to identify and manage obstetric complications, educate women about risks during pregnancy and promote skilled birth attendance during childbirth. The aim of this study was to assess women's knowledge of obstetric danger signs and factors associated with this knowledge in Ambanja, Madagascar. It also sought to evaluate whether the participation in a mobile health (mHealth) project that aimed to provide comprehensive ANC to pregnant women in remote areas influenced women's knowledge of obstetric danger signs. From April to October 2015, a non-random, convenience sample of 372 women in their first year postpartum were recruited, including 161 who had participated in the mHealth project. Data were analyzed using bivariate and multivariate logistic regression. Knowledge of at least one danger sign varied from 80.9% of women knowing danger sign(s) in pregnancy, to 51.9%, 50.8% and 53.2% at delivery, postpartum and in the newborn, respectively. Participation in the mHealth intervention, higher household income, and receipt of information about danger signs during pregnancy were associated with knowledge of danger signs during delivery, in bivariate analysis; only higher household income and mHealth project participation were independently associated. Higher educational attainment and receipt of information about danger signs in antenatal care were associated with significantly higher odds of knowing danger sign(s) for the newborn in both bivariate and multivariate analysis. Knowledge of obstetric danger signs is low. Information provision during pregnancy and with mHealth is promising. This trial was retrospectively registered at the International Standard Randomized Controlled Trial Register (identifier ISRCTN15798183 ; August 22, 2015).

Noise exposure immediately activates cochlear mitogen-activated protein kinase signaling

Directory of Open Access Journals (Sweden)

Kumar N Alagramam

2014-01-01

Full Text Available Noise-induced hearing loss (NIHL is a major public health issue worldwide. Uncovering the early molecular events associated with NIHL would reveal mechanisms leading to the hearing loss. Our aim is to investigate the immediate molecular responses after different levels of noise exposure and identify the common and distinct pathways that mediate NIHL. Previous work showed mice exposed to 116 decibels sound pressure level (dB SPL broadband noise for 1 h had greater threshold shifts than the mice exposed to 110 dB SPL broadband noise, hence we used these two noise levels in this study. Groups of 4-8-week-old CBA/CaJ mice were exposed to no noise (control or to broadband noise for 1 h, followed by transcriptome analysis of total cochlear RNA isolated immediately after noise exposure. Previously identified and novel genes were found in all data sets. Following exposure to noise at 116 dB SPL, the earliest responses included up-regulation of 243 genes and down-regulation of 61 genes, while a similar exposure at 110 dB SPL up-regulated 155 genes and down-regulated 221 genes. Bioinformatics analysis indicated that mitogen-activated protein kinase (MAPK signaling was the major pathway in both levels of noise exposure. Nevertheless, both qualitative and quantitative differences were noticed in some MAPK signaling genes, after exposure to different noise levels. Cacna1b , Cacna1g , and Pla2g6 , related to calcium signaling were down-regulated after 110 dB SPL exposure, while the fold increase in the expression of Fos was relatively lower than what was observed after 116 dB SPL exposure. These subtle variations provide insight on the factors that may contribute to the differences in NIHL despite the activation of a common pathway.

Rift-drift transition in the Dangerous Grounds, South China Sea

Science.gov (United States)

Peng, Xi; Shen, Chuanbo; Mei, Lianfu; Zhao, Zhigang; Xie, Xiaojun

2018-04-01

The South China Sea (SCS) has a long record of rifting before and after subsequent seafloor spreading, affecting the wide continent of the Dangerous Grounds, and its scissor-shape opening manner results in the rifting structures that vary along this margin. Some 2000 km of regional multichannel seismic data combined with borehole and dredge data are interpreted to analyze the multistage rifting process, structural architecture and dynamic evolution across the entire Dangerous Grounds. Key sequence boundaries above the Cenozoic basement are identified and classified into the breakup unconformity and the rift end unconformity, which consist of the rift-related unconformities. Reflector T70 in the east of the Dangerous Grounds represents the breakup unconformity, which is likely corresponding to the spreading of the East Subbasin. T60 formed on the top of carbonate platform is time equivalent to the spreading of the Southwest Subbasin, marking the breakup unconformity of the central Dangerous Grounds. The termination of the spreading of the SCS is manifested by the rift end unconformity of T50 in the southwest and the final rift occurring in the northwest of the Dangerous Grounds is postponed to the rift end unconformity of T40. On the basis of the stratigraphic and structural analysis, distinct segments in the structural architecture of the syn-rift units and the ages of rift-drift transition show obvious change from the proximal zone to the distal zone. Three domains, which are the Reed Bank-Palawan Rift domain, the Dangerous Grounds Central Detachment domain and Nam Con Son Exhumation domain, reflect the propagation of the margin rifting developed initially by grabens formed by high angle faults, then large half-grabens controlled by listric faults and detachments and finally rotated fault blocks in the hyper-extended upper crust associated with missing lower crust or exhumed mantle revealing a migration and stepwise rifting process in the south margin of the SCS.

Dangerousness and mental health policy.

Science.gov (United States)

Hewitt, J L

2008-04-01

Mental health policy development in the UK has become increasingly dominated by the assumed need to prevent violence and alleviate public concerns about the dangers of the mentally ill living in the community. Risk management has become the expected focus of contemporary mental health services, and responsibility has increasingly been devolved to individual service professionals when systems fail to prevent violence. This paper analyses the development of mental health legislation and its impact on services users and mental health professionals at the micro level of service delivery. Historical precedence, media influence and public opinion are explored, and the reification of risk is questioned in practical and ethical terms. The government's newest proposals for compulsory treatment in the community are discussed in terms of practical efficacy and therapeutic impact. Dangerousness is far from being an objectively observable phenomenon arising from clinical pathology, but is a formulation of what is partially knowable through social analysis and unknowable by virtue of its situation in individual psychic motivation. Risk assessment can therefore never be completely accurate, and the solution of a 'better safe than sorry' approach to mental health policy is ethically and pragmatically flawed.

HeadsUp: Keeping Pedestrian Phone Addicts from Dangers Using Mobile Phone Sensors

OpenAIRE

Zhou, Zhengjuan

2015-01-01

Walking while staring at the mobile phone is dangerous, and the danger mainly arises from distraction. While watching the mobile phone, one could fall into a deep well without noticing the manhole cover was missing, one could be hit by a rushing car without observing the traffic light, and so forth. Some mobile phone users are already aware of the crisis, and they keep looking up and down to allocate some focus to danger spying; however, the statistics data revealed by US government make such...

FIRES: Fire Information Retrieval and Evaluation System - A program for fire danger rating analysis

Science.gov (United States)

Patricia L. Andrews; Larry S. Bradshaw

1997-01-01

A computer program, FIRES: Fire Information Retrieval and Evaluation System, provides methods for evaluating the performance of fire danger rating indexes. The relationship between fire danger indexes and historical fire occurrence and size is examined through logistic regression and percentiles. Historical seasonal trends of fire danger and fire occurrence can be...

Nonreciprocal signal routing in an active quantum network

Science.gov (United States)

Metelmann, A.; Türeci, H. E.

2018-04-01

As superconductor quantum technologies are moving towards large-scale integrated circuits, a robust and flexible approach to routing photons at the quantum level becomes a critical problem. Active circuits, which contain parametrically driven elements selectively embedded in the circuit, offer a viable solution. Here, we present a general strategy for routing nonreciprocally quantum signals between two sites of a given lattice of oscillators, implementable with existing superconducting circuit components. Our approach makes use of a dual lattice of overdamped oscillators linking the nodes of the main lattice. Solutions for spatially selective driving of the lattice elements can be found, which optimally balance coherent and dissipative hopping of microwave photons to nonreciprocally route signals between two given nodes. In certain lattices these optimal solutions are obtained at the exceptional point of the dynamical matrix of the network. We also demonstrate that signal and noise transmission characteristics can be separately optimized.

2012 drug packaging review: many dangerous, reportable flaws.

Science.gov (United States)

2013-05-01

Drug packaging plays an important role in protecting and providing information to patients. The packaging examined by Prescrire in 2012, on the whole, still fails to perform all of these functions effectively. Two issues are especially worrisome. First, packaging too often poses a danger to children. In addition, too many patient leaflets provide incomplete information about adverse effects, thus failing to properly protect the most vulnerable patients. Yet, the method Prescrire used to analyse drug packaging shows that it is not difficult to detect and anticipate risks. It is up to healthcare professionals to take advantage of the method, to protect patients from, and report, dangerous packaging.

The Dangers of Aestheticism in Schooling.

Science.gov (United States)

Meager, Ruby

1981-01-01

Prompted by Immanuel Kant's analysis of the nature and operations of the imagination in his "Critique of the Aesthetical Judgment," this article points out the danger of encouraging imagination-borne aesthetical judgments and explanatory hypotheses. Concludes that understanding requires submission to more stringent standards of objectivity and to…

Dangers of peace journalism

Directory of Open Access Journals (Sweden)

Wilhelm Kempf

2016-10-01

Full Text Available The sense of mission shared by some peace journalists is a dangerous attitude. All journalists can do to give peace a chance is to serve as mediators, helping conflict parties overcome the competitive misperceptions and societal beliefs that fuel conflict. If peace journalists try to promote and impose their own solutions, however, frustration is inevitable and will finally result in the search for an evildoer who can be made responsible. Thus by involving themselves in conflicts, journalists can become unintentional agents of conflict escalation.

Regulations on handling dangerous objects in Japan (with particular reference to sodium)

International Nuclear Information System (INIS)

Nagai, M.

1971-01-01

Sodium is designated as a kind of dangerous object, so that special care has to be taken in handling or storing large amounts of sodium. Formal regulations on sodium handling in Japan are prescribed in Fire Service Law, which is supplemented by Rules on Handling Dangerous Objects. Since these regulations are not intended to be applied to large sodium circuits, some defects and inappropriate expressions might be found in them. An attempt is made here to pick up these problems and important points from Japanese regulations on handling dangerous objects with particular reference to sodium

Evaluating fire danger in Brazilian biomes: present and future patterns

Science.gov (United States)

Silva, Patrícia; Bastos, Ana; DaCamara, Carlos; Libonati, Renata

2017-04-01

Climate change is expected to have a significant impact on fire occurrence and activity, particularly in Brazil, a region known to be fire-prone [1]. The Brazilian savanna, commonly referred to as cerrado, is a fire-adapted biome covering more than 20% of the country's total area. It presents the highest numbers of fire events, making it particularly susceptible to changes in climate. It is thus essential to understand the present fire regimes in Brazilian biomes, in order to better evaluate future patterns. The CPTEC/INPE, the Brazilian Center for Weather Forecasting and Climate Research at the Brazilian National Institute of Space Research developed a fire danger index based on the occurrence of hundreds of thousands of fire events in the main Brazilian biomes [2]: the Meteorological Fire Danger Index (MFDI). This index indicates the predisposition of vegetation to be burned on a given day, for given climate conditions preceding that day. It relies on daily values of air temperature, relative humidity, accumulated precipitation and vegetation cover. In this study we aim to access the capability of the MFDI to accurately replicate present fire conditions for different biomes, with a special focus on cerrado. To this end, we assess the link between the MFDI as calculated by three different reanalysis (ERA-Interim, NCEP/DOE Reanalysis 2 and MERRA-2) and the observed burned area. We further calculate the validated MFDI using a regional climate model, the RCA4 as forced by EC-Earth from CORDEX, to understand the ability of the model to characterize present fire danger. Finally, the need to calibrate the model to better characterize future fire danger was also evaluated. This work was developed within the framework of the Brazilian Fire-Land-Atmosphere System (BrFLAS) Project financed by the Portuguese and Brazilian science foundations, FCT and FAPESP (project references FAPESP/1389/2014 and 2014/20042-2). [1] KRAWCHUK, M.A.; MORITZ, M.A.; PARISIEN, M.A.; VAN DORN, J

Phenobarbital indirectly activates the constitutive active androstane receptor (CAR) by inhibition of epidermal growth factor receptor signaling.

Science.gov (United States)

Mutoh, Shingo; Sobhany, Mack; Moore, Rick; Perera, Lalith; Pedersen, Lee; Sueyoshi, Tatsuya; Negishi, Masahiko

2013-05-07

Phenobarbital is a central nervous system depressant that also indirectly activates nuclear receptor constitutive active androstane receptor (CAR), which promotes drug and energy metabolism, as well as cell growth (and death), in the liver. We found that phenobarbital activated CAR by inhibiting epidermal growth factor receptor (EGFR) signaling. Phenobarbital bound to EGFR and potently inhibited the binding of EGF, which prevented the activation of EGFR. This abrogation of EGFR signaling induced the dephosphorylation of receptor for activated C kinase 1 (RACK1) at Tyr(52), which then promoted the dephosphorylation of CAR at Thr(38) by the catalytic core subunit of protein phosphatase 2A. The findings demonstrated that the phenobarbital-induced mechanism of CAR dephosphorylation and activation is mediated through its direct interaction with and inhibition of EGFR.

Nonradioactive Dangerous Waste Landfill sampling and analysis plan and data quality objectives process summary report

International Nuclear Information System (INIS)

Smith, R.C.

1997-08-01

This sampling and analysis plan defines the sampling and analytical activities and associated procedures that will be used to support the Nonradioactive Dangerous Waste Landfill soil-gas investigation. This SAP consists of three sections: this introduction, the field sampling plan, and the quality assurance project plan. The field sampling plan defines the sampling and analytical methodologies to be performed

Social referencing and child anxiety: the evolutionary based role of fathers' versus mothers' signals

NARCIS (Netherlands)

Möller, E.L.; Majdandžić, M.; Vriends, N.; Bögels, S.M.

2014-01-01

Children use signals from others to guide their behavior when confronted with potentially dangerous situations, so called social referencing. Due to evolutionary based different expertise of fathers and mothers, parents might be different social references for their children. The present study

Key mediators of intracellular amino acids signaling to mTORC1 activation.

Science.gov (United States)

Duan, Yehui; Li, Fengna; Tan, Kunrong; Liu, Hongnan; Li, Yinghui; Liu, Yingying; Kong, Xiangfeng; Tang, Yulong; Wu, Guoyao; Yin, Yulong

2015-05-01

Mammalian target of rapamycin complex 1 (mTORC1) is activated by amino acids to promote cell growth via protein synthesis. Specifically, Ras-related guanosine triphosphatases (Rag GTPases) are activated by amino acids, and then translocate mTORC1 to the surface of late endosomes and lysosomes. Ras homolog enriched in brain (Rheb) resides on this surface and directly activates mTORC1. Apart from the presence of intracellular amino acids, Rag GTPases and Rheb, other mediators involved in intracellular amino acid signaling to mTORC1 activation include human vacuolar sorting protein-34 (hVps34) and mitogen-activating protein kinase kinase kinase kinase-3 (MAP4K3). Those molecular links between mTORC1 and its mediators form a complicate signaling network that controls cellular growth, proliferation, and metabolism. Moreover, it is speculated that amino acid signaling to mTORC1 may start from the lysosomal lumen. In this review, we discussed the function of these mediators in mTORC1 pathway and how these mediators are regulated by amino acids in details.

Study on acoustic emission signals of active defect in pressure piping under hydraulic pressure

International Nuclear Information System (INIS)

Ai Qiong; Liu Caixue; Wang Yao; He Pan; Song Jian

2009-01-01

Experimental investigations of acoustic emission (AE) of active defect in pressure piping with a prefabricated crack under hydraulic pressure tester were conducted. AE signals of fatigue-crack-growth in pressure piping were monitored incessantly in all processes, and all signals recorded were analyzed and processed. The result of signal processing show that the amplitude and energy of acoustic emission signals from defect in pressure pipeline increase gradually with the load time, and thus the active defects in pipeline can be identified; the amplitude, energy and count of acoustic emission signals increase sharply before the defect runs through, and we can forecast the penetrated leakage of pipeline. (authors)

Immune activation by histones: plusses and minuses in inflammation.

Science.gov (United States)

Pisetsky, David S

2013-12-01

Histones are highly cationic proteins that are essential components of the cell nucleus, interacting with DNA to form the nucleosome and regulating transcription. Histones, however, can transit from the cell nucleus during cell death and, once in an extracellular location, can serve as danger signals and activate immune cells. An article in this issue of the European Journal of Immunology [Eur. J. Immunol. 2013. 43: 3336-3342] reports that histones can activate monocyte-derived DCs via the NRLP3 inflammasome to induce the production of IL-1β. As such, histones, which can also stimulate TLRs, may drive events in the immunopathogenesis of a wide range of acute and chronic diseases marked by sterile inflammation. While the mechanism of this stimulation is not known, the positive charge of histones may provide a structural element to promote interaction with cells and activation of downstream signaling systems. © 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim.

Dangers of environmental pollution

International Nuclear Information System (INIS)

Schaer, M.

1978-01-01

Environmental pollution is ever increasing. Protection of the environment must not be neglected for economic reasons. Damage to health due to environmental effects is hard to determine epidemiologically as there are nearly always several causes to consider at the same time. Still, the increase in environmental pollution results in increased damage to humans, animals, and plants. The many dangers to health can be illustrated by the example of energy demand and the different ways to meet it. It is highly necessary to create environmental laws which aim at a reduction of environmental pollution. (orig.) [de

EG-1 interacts with c-Src and activates its signaling pathway.

Science.gov (United States)

Lu, Ming; Zhang, Liping; Sartippour, Maryam R; Norris, Andrew J; Brooks, Mai N

2006-10-01

EG-1 is significantly elevated in breast, colorectal, and prostate cancers. Overexpression of EG-1 stimulates cellular proliferation, and targeted inhibition blocks mouse xenograft tumor growth. To further clarify the function of EG-1, we investigated its role in c-Src activation. We observed that EG-1 overexpression results in activation of c-Src, but found no evidence that EG-1 is a direct Src substrate. EG-1 also binds to other members of the Src family. Furthermore, EG-1 shows interaction with multiple other SH3- and WW-containing molecules involved in various signaling pathways. These observations suggest that EG-1 may be involved in signaling pathways including c-Src activation.

Augustine on the Dangers of Friendship

NARCIS (Netherlands)

Nawar, Tamer

2015-01-01

The philosophers of antiquity had much to say about the place of friendship in the good life and its role in helping us live virtuously. Augustine is unusual in giving substantial attention to the dangers of friendship and its potential to serve as an obstacle (rather than an aid) to virtue. Despite

Activation of Wnt/β-catenin signalling is required for TGF-β/Smad2/3 signalling during myofibroblast proliferation.

Science.gov (United States)

Xu, Liang; Cui, Wen-Hui; Zhou, Wen-Cheng; Li, De-Lin; Li, Liu-Cheng; Zhao, Ping; Mo, Xiao-Ting; Zhang, Zhihui; Gao, Jian

2017-08-01

Fibrosis in animal models and human diseases is associated with aberrant activation of the Wnt/β-catenin pathway. Despite extensive research efforts, effective therapies are still not available. Myofibroblasts are major effectors, responsible for extracellular matrix deposition. Inhibiting the proliferation of the myofibroblast is crucial for treatment of fibrosis. Proliferation of myofibroblasts can have many triggering effects that result in fibrosis. In recent years, the Wnt pathway has been studied as an underlying factor as a primary contributor to fibrotic diseases. These efforts notwithstanding, the specific mechanisms by which Wnt-mediated promotes fibrosis reaction remain obscure. The central role of the transforming growth factor-β (TGF-β) and myofibroblast activity in the pathogenesis of fibrosis has become generally accepted. The details of interaction between these two processes are not obvious. The present investigation was conducted to evaluate the level of sustained expression of fibrosis iconic proteins (vimentin, α-SMA and collagen I) and the TGF-β signalling pathway that include smad2/3 and its phosphorylated form p-smad2/3. Detailed analysis of the possible molecular mechanisms mediated by β-catenin revealed epithelial-mesenchymal transition and additionally demonstrated transitions of fibroblasts to myofibroblast cell forms, along with increased activity of β-catenin in regulation of the signalling network, which acts to counteract autocrine TGF-β/smad2/3 signalling. A major outcome of this study is improved insight into the mechanisms by which epithelial and mesenchymal cells activated by TGFβ1-smad2/3 signalling through Wnt/β-catenin contribute to lung fibrosis. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Liability in maritime transport of dangerous goods

International Nuclear Information System (INIS)

Feldhaus, H.

1985-01-01

The first part contains a description of national liability standards for maritime transport in the French, English, US-American and West German legislation. This is followed up by a detailed review of the existing international agreements. The book is rounded off by a critical evaluation of the presently held discussion and suggested solutions on the problems of liability in the maritime transport of dangerous goods other than mineral oil. The author takes a close look at the 'Entwurf eines Internationalen Uebereinkommens ueber die Haftung und den Schadenersatz bei der Befoerderung schaedlicher und gefaehrlicher Stoffe auf See' ('draft of an international agreement on liability and compensation for damage in maritime transport of noxious and dangerous goods') in the version of May 23, 1983, which was discussed on an international diplomat's conference in London without however, yielding any concrete results. (orig./HP) [de

Peroxisome proliferator-activated receptor gamma signaling in human sperm physiology.

Science.gov (United States)

Liu, Li-Li; Xian, Hua; Cao, Jing-Chen; Zhang, Chong; Zhang, Yong-Hui; Chen, Miao-Miao; Qian, Yi; Jiang, Ming

2015-01-01

Peroxisome proliferator-activated receptor gamma (PPARγ) is a member of the PPARs, which are transcription factors of the steroid receptor superfamily. PPARγ acts as an important molecule for regulating energy homeostasis, modulates the hypothalamic-pituitary-gonadal (HPG) axis, and is reciprocally regulated by HPG. In the human, PPARγ protein is highly expressed in ejaculated spermatozoa, implying a possible role of PPARγ signaling in regulating sperm energy dissipation. PPARγ protein is also expressed in Sertoli cells and germ cells (spermatocytes). Its activation can be induced during capacitation and the acrosome reaction. This mini-review will focus on how PPARγ signaling may affect fertility and sperm quality and the potential reversibility of these adverse effects.

224-T Transuranic Waste Storage and Assay Facility dangerous waste permit application

International Nuclear Information System (INIS)

1992-01-01

Westinghouse Hanford Company is a major contractor to the US Department of Energy Richland Field Office and serves as cooperator of the 224-T Transuranic Waste Storage and Assay Facility, the storage unit addressed in this permit application. At the time of submission of this portion of the Hanford Facility. Dangerous Waste Permit Application covering the 224-T Transuranic Waste Storage and Assay Facility, many issues identified in comments to the draft Hanford Facility Dangerous Waste Permit remain unresolved. This permit application reflects the positions taken by the US Department of Energy, Company on the draft Hanford Facility Dangerous Waste Permit and may not be read to conflict with those comments. The 224-T Transuranic Waste Storage and Assay Facility Dangerous Waste Permit Application (Revision 0) consists of both a Part A and Part B permit application. An explanation of the Part A revisions associated with this unit, including the Part A revision currently in effect, is provided at the beginning of the Part A section. The Part B consists of 15 chapters addressing the organization and content of the Part B Checklist prepared by the Washington State Department of Ecology (Ecology 1987). The 224-T Transuranic Waste Storage and Assay Facility Dangerous Waste Permit Application contains information current as of March 1, 1992

Liquid effluent retention facility dangerous waste permit application

International Nuclear Information System (INIS)

1991-06-01

This appendix to the Liquid Effluent Retention Facility Dangerous Waste Permit Application contains pumps, piping, leak detection systems, geomembranes, leachate collection systems, earthworks and floating cover systems

Hanford facility dangerous waste permit application, general information portion. Revision 3

International Nuclear Information System (INIS)

Sonnichsen, J.C.

1997-01-01

For purposes of the Hanford facility dangerous waste permit application, the US Department of Energy's contractors are identified as ''co-operators'' and sign in that capacity (refer to Condition I.A.2. of the Dangerous Waste Portion of the Hanford Facility Resource Conservation and Recovery Act Permit). Any identification of these contractors as an ''operator'' elsewhere in the application is not meant to conflict with the contractors' designation as co-operators but rather is based on the contractors' contractual status with the U.S. Department of Energy, Richland Operations Office. The Dangerous Waste Portion of the initial Hanford Facility Resource Conservation and Recovery Act Permit, which incorporated five treatment, storage, and/or disposal units, was based on information submitted in the Hanford Facility Dangerous Waste Permit Application and in closure plan and closure/postclosure plan documentation. During 1995, the Dangerous Waste Portion was modified twice to incorporate another eight treatment, storage, and/or disposal units; during 1996, the Dangerous Waste Portion was modified once to incorporate another five treatment, storage, and/or disposal units. The permit modification process will be used at least annually to incorporate additional treatment, storage, and/or disposal units as permitting documentation for these units is finalized. The units to be included in annual modifications are specified in a schedule contained in the Dangerous Waste Portion of the Hanford Facility Resource Conservation and Recovery Act Permit. Treatment, storage, and/or disposal units will remain in interim status until incorporated into the Permit. The Hanford Facility Dangerous Waste Permit Application is considered to be a single application organized into a General Information Portion (this document, DOE/RL-91-28) and a Unit-Specific Portion. The scope of the Unit-Specific Portion is limited to individual operating treatment, storage, and/or disposal units for which

Hanford facility dangerous waste permit application, general information portion. Revision 3

Energy Technology Data Exchange (ETDEWEB)

Sonnichsen, J.C.

1997-08-21

For purposes of the Hanford facility dangerous waste permit application, the US Department of Energy`s contractors are identified as ``co-operators`` and sign in that capacity (refer to Condition I.A.2. of the Dangerous Waste Portion of the Hanford Facility Resource Conservation and Recovery Act Permit). Any identification of these contractors as an ``operator`` elsewhere in the application is not meant to conflict with the contractors` designation as co-operators but rather is based on the contractors` contractual status with the U.S. Department of Energy, Richland Operations Office. The Dangerous Waste Portion of the initial Hanford Facility Resource Conservation and Recovery Act Permit, which incorporated five treatment, storage, and/or disposal units, was based on information submitted in the Hanford Facility Dangerous Waste Permit Application and in closure plan and closure/postclosure plan documentation. During 1995, the Dangerous Waste Portion was modified twice to incorporate another eight treatment, storage, and/or disposal units; during 1996, the Dangerous Waste Portion was modified once to incorporate another five treatment, storage, and/or disposal units. The permit modification process will be used at least annually to incorporate additional treatment, storage, and/or disposal units as permitting documentation for these units is finalized. The units to be included in annual modifications are specified in a schedule contained in the Dangerous Waste Portion of the Hanford Facility Resource Conservation and Recovery Act Permit. Treatment, storage, and/or disposal units will remain in interim status until incorporated into the Permit. The Hanford Facility Dangerous Waste Permit Application is considered to be a single application organized into a General Information Portion (this document, DOE/RL-91-28) and a Unit-Specific Portion. The scope of the Unit-Specific Portion is limited to individual operating treatment, storage, and/or disposal units for which

DMPD: Multiple signaling pathways leading to the activation of interferon regulatoryfactor 3. [Dynamic Macrophage Pathway CSML Database

Lifescience Database Archive (English)

Full Text Available 12213596 Multiple signaling pathways leading to the activation of interferon regula...(.html) (.csml) Show Multiple signaling pathways leading to the activation of interferon regulatoryfactor 3.... PubmedID 12213596 Title Multiple signaling pathways leading to the activation of

Activation of Wnt Signaling in Cortical Neurons Enhances Glucose Utilization through Glycolysis.

Science.gov (United States)

Cisternas, Pedro; Salazar, Paulina; Silva-Álvarez, Carmen; Barros, L Felipe; Inestrosa, Nibaldo C

2016-12-09

The Wnt signaling pathway is critical for a number of functions in the central nervous system, including regulation of the synaptic cleft structure and neuroprotection against injury. Deregulation of Wnt signaling has been associated with several brain pathologies, including Alzheimer's disease. In recent years, it has been suggested that the Wnt pathway might act as a central integrator of metabolic signals from peripheral organs to the brain, which would represent a new role for Wnt signaling in cell metabolism. Energy metabolism is critical for normal neuronal function, which mainly depends on glucose utilization. Brain energy metabolism is important in almost all neurological disorders, to which a decrease in the capacity of the brain to utilize glucose has been linked. However, little is known about the relationship between Wnt signaling and neuronal glucose metabolism in the cellular context. In the present study, we found that acute treatment with the Wnt3a ligand induced a large increase in glucose uptake, without changes in the expression or localization of glucose transporter type 3. In addition, we observed that Wnt3a treatment increased the activation of the metabolic sensor Akt. Moreover, we observed an increase in the activity of hexokinase and in the glycolytic rate, and both processes were dependent on activation of the Akt pathway. Furthermore, we did not observe changes in the activity of glucose-6-phosphate dehydrogenase or in the pentose phosphate pathway. The effect of Wnt3a was independent of both the transcription of Wnt target genes and synaptic effects of Wnt3a. Together, our results suggest that Wnt signaling stimulates glucose utilization in cortical neurons through glycolysis to satisfy the high energy demand of these cells. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

β1-adrenergic receptors activate two distinct signaling pathways in striatal neurons

Science.gov (United States)

Meitzen, John; Luoma, Jessie I.; Stern, Christopher M.; Mermelstein, Paul G.

2010-01-01

Monoamine action in the dorsal striatum and nucleus accumbens plays essential roles in striatal physiology. Although research often focuses on dopamine and its receptors, norepinephrine and adrenergic receptors are also crucial in regulating striatal function. While noradrenergic neurotransmission has been identified in the striatum, little is known regarding the signaling pathways activated by β-adrenergic receptors in this brain region. Using cultured striatal neurons, we characterized a novel signaling pathway by which activation of β1-adrenergic receptors leads to the rapid phosphorylation of cAMP Response Element Binding Protein (CREB), a transcription-factor implicated as a molecular switch underlying long-term changes in brain function. Norepinephrine-mediated CREB phosphorylation requires β1-adrenergic receptor stimulation of a receptor tyrosine kinase, ultimately leading to the activation of a Ras/Raf/MEK/MAPK/MSK signaling pathway. Activation of β1-adrenergic receptors also induces CRE-dependent transcription and increased c-fos expression. In addition, stimulation of β1-adrenergic receptors produces cAMP production, but surprisingly, β1-adrenergic receptor activation of adenylyl cyclase was not functionally linked to rapid CREB phosphorylation. These findings demonstrate that activation of β1-adrenergic receptors on striatal neurons can stimulate two distinct signaling pathways. These adrenergic actions can produce long-term changes in gene expression, as well as rapidly modulate cellular physiology. By elucidating the mechanisms by which norepinephrine and β1-adrenergic receptor activation affects striatal physiology, we provide the means to more fully understand the role of monoamines in modulating striatal function, specifically how norepinephrine and β1-adrenergic receptors may affect striatal physiology. PMID:21143600

Teens and Steroids: A Dangerous Combo

Science.gov (United States)

... Endocrinology Products, warns teens and parents about the dangers of steroid use. Q: What are anabolic steroids ... لعربية | Kreyòl Ayisyen | Français | Polski | Português | Italiano | Deutsch | 日本語 | ف ...

NLRP3 inflammasome: From a danger signal sensor to a regulatory node of oxidative stress and inflammatory diseases

Directory of Open Access Journals (Sweden)

Amna Abderrazak

2015-04-01

An ever increasing number of studies link the sensing of cellular stress signals to a direct pathophysiological role of NLRP3 activation in a wide range of autoinflammatory and autoimmune disorders, and thus provide a novel mechanistic rational, on how molecules trigger and support sterile inflammatory diseases. A vast interest has created to unravel how NLRP3 becomes activated, since mechanistic insight is the prerequisite for a knowledge-based development of therapeutic intervention strategies that specifically target the NLRP3 triggered IL-1β production. In this review, we have updated knowledge on NLRP3 inflammasome assembly and activation and on the pyrin domain in NLRP3 that could represent a drug target to treat sterile inflammatory diseases. We have reported mutations in NLRP3 that were found to be associated with certain diseases. In addition, we have reviewed the functional link between NLRP3 inflammasome, the regulator of cellular redox status Trx/TXNIP complex, endoplasmic reticulum stress and the pathogenesis of diseases such as type 2 diabetes. Finally, we have provided data on NLRP3 inflammasome, as a critical regulator involved in the pathogenesis of obesity and cardiovascular diseases.

Mental Health and Teens: Watch for Danger Signs

Science.gov (United States)

... Gradeschool Teen Dating & Sex Fitness Nutrition Driving Safety School Substance Use Young Adult Healthy Children > Ages & Stages > Teen > Mental Health and Teens: Watch for Danger Signs Ages & Stages ...

The lack of autophagy triggers precocious activation of Notch signaling during Drosophila oogenesis

Directory of Open Access Journals (Sweden)

Barth Julia MI

2012-12-01

Full Text Available Abstract Background The proper balance of autophagy, a lysosome-mediated degradation process, is indispensable for oogenesis in Drosophila. We recently demonstrated that egg development depends on autophagy in the somatic follicle cells (FC, but not in the germline cells (GCs. However, the lack of autophagy only affects oogenesis when FCs are autophagy-deficient but GCs are wild type, indicating that a dysfunctional signaling between soma and germline may be responsible for the oogenesis defects. Thus, autophagy could play an essential role in modulating signal transduction pathways during egg development. Results Here, we provide further evidence for the necessity of autophagy during oogenesis and demonstrate that autophagy is especially required in subsets of FCs. Generation of autophagy-deficient FCs leads to a wide range of phenotypes that are similar to mutants with defects in the classical cell-cell signaling pathways in the ovary. Interestingly, we observe that loss of autophagy leads to a precocious activation of the Notch pathway in the FCs as monitored by the expression of Cut and Hindsight, two downstream effectors of Notch signaling. Conclusion Our findings point to an unexpected function for autophagy in the modulation of the Notch signaling pathway during Drosophila oogenesis and suggest a function for autophagy in proper receptor activation. Egg development is affected by an imbalance of autophagy between signal sending (germline and signal receiving cell (FC, thus the lack of autophagy in the germline is likely to decrease the amount of active ligand and accordingly compensates for increased signaling in autophagy-defective follicle cells.

Aberrant neuronal activity-induced signaling and gene expression in a mouse model of RASopathy.

Directory of Open Access Journals (Sweden)

Franziska Altmüller

2017-03-01

Full Text Available Noonan syndrome (NS is characterized by reduced growth, craniofacial abnormalities, congenital heart defects, and variable cognitive deficits. NS belongs to the RASopathies, genetic conditions linked to mutations in components and regulators of the Ras signaling pathway. Approximately 50% of NS cases are caused by mutations in PTPN11. However, the molecular mechanisms underlying cognitive impairments in NS patients are still poorly understood. Here, we report the generation and characterization of a new conditional mouse strain that expresses the overactive Ptpn11D61Y allele only in the forebrain. Unlike mice with a global expression of this mutation, this strain is viable and without severe systemic phenotype, but shows lower exploratory activity and reduced memory specificity, which is in line with a causal role of disturbed neuronal Ptpn11 signaling in the development of NS-linked cognitive deficits. To explore the underlying mechanisms we investigated the neuronal activity-regulated Ras signaling in brains and neuronal cultures derived from this model. We observed an altered surface expression and trafficking of synaptic glutamate receptors, which are crucial for hippocampal neuronal plasticity. Furthermore, we show that the neuronal activity-induced ERK signaling, as well as the consecutive regulation of gene expression are strongly perturbed. Microarray-based hippocampal gene expression profiling revealed profound differences in the basal state and upon stimulation of neuronal activity. The neuronal activity-dependent gene regulation was strongly attenuated in Ptpn11D61Y neurons. In silico analysis of functional networks revealed changes in the cellular signaling beyond the dysregulation of Ras/MAPK signaling that is nearly exclusively discussed in the context of NS at present. Importantly, changes in PI3K/AKT/mTOR and JAK/STAT signaling were experimentally confirmed. In summary, this study uncovers aberrant neuronal activity

Danger, hazard, risk

International Nuclear Information System (INIS)

Kafka, P.

1992-01-01

The real conditions covered by technical safety studies are described better by the term 'risk' instead of such qualitative terms as 'danger' or 'hazard'. 'Risk' incorporates not only the type of damage, the onset of damage, the probability of damage occurring, but also the extent of damage. In reliability and safety engineering, a probabilistic safety analysis is able to describe a plant most comprehensively by these three elements: What can happen? How frequently will it occur? What are the impacts to be taken into account? PSA is meaningful not only when applied to such technical areas in which there is a risk potential; the holistic analytical process optimizes any kind of system and plant in terms of availability and technical safety. (orig.) [de

Activation of PERK signaling through fluoride-mediated endoplasmic reticulum stress in OS732 cells

International Nuclear Information System (INIS)

Xu, Hui; Zhou, Yu-lai; Zhang, Xiu-yun; Lu, Peng; Li, Guang-sheng

2010-01-01

Our proteomical analysis of osteoblasts exposed to fluoride revealed a distinctive upregulation of proteins in osteoblast. These upregulated proteins play key roles in the protein folding. The PRK-like ER kinase (PERK) signaling, one branch of unfolded protein response (UPR) to combat ER stress, is a transcription factor needed for osteoblast proliferation and differentiation. The mechanism of skeletal fluorosis by which fluoride regulates osteoblast is not fully defined. Here we studied the effect of fluoride on PERK signaling genes and x-box binding protein 1 (xbp-1) in OS7232 cells (human osteoblast-like cell line). Meantime, genes associated with bone turnover were examined in this study. We found that early and continuous fluoride exposure increased the binding immunoglobulin protein (BiP) expression and activated the PERK signaling pathway, resulting in activation of transcription factor 4 (ATF4) and nuclear factor erythroid 2-related factor 2 (Nrf2). The altered expression of cbfa1, osteoprotegerin (OPG)/nuclear factor kappa B ligand (RANKL) were viewed in this study. These results showed fluoride impelled a distinctive ER stress response in OS732 cells, primarily by activating PERK and PERK-dependent signaling. Little effects were viewed for activating xbp-1, a common target of the other two canonical sensors of ER stress, ATF6 and IRE1. In this study the altered expression of bone turnover genes were consistent with activation of ER stress and PERK signaling. This study proved that PERK signaling play major roles in action of fluoride on osteoblast, and suggested that bone response in skeletal fluorosis may be due in part to PERK signaling pathway.

Danger Signs of Childhood Pneumonia: Caregiver Awareness and Care Seeking Behavior in a Developing Country

Directory of Open Access Journals (Sweden)

Ikenna K. Ndu

2015-01-01

Full Text Available Background. Efforts to reduce child mortality especially in Africa must as a necessity aim to decrease mortality due to pneumonia. To achieve this, preventive strategies such as expanding vaccination coverage are key. However once a child develops pneumonia prompt treatment which is essential to survival is dependent on mothers and caregiver recognition of the symptoms and danger signs of pneumonia. Methods. This community based cross-sectional study enrolled four hundred and sixty-six caregivers in Enugu state. It aimed to determine knowledge of caregivers about danger signs of pneumonia and the sociodemographic factors that influence knowledge and care seeking behaviour of caregivers. Results. There is poor knowledge of the aetiology and danger signs of pneumonia among caregivers. Higher maternal educational attainment and residence in semiurban area were significantly associated with knowledge of aetiology, danger signs, and vaccination of their children against pneumonia. Fast breathing and difficulty in breathing were the commonest known and experienced WHO recognized danger signs while fever was the commonest perceived danger sign among caregivers. Conclusion. Knowledge of danger signs and health seeking behaviour among caregivers is inadequate. There is need for intensified public and hospital based interventions targeted at mothers to improve their knowledge about pneumonia.

Stretch activates human myometrium via ERK, caldesmon and focal adhesion signaling.

Directory of Open Access Journals (Sweden)

Yunping Li

2009-10-01

Full Text Available An incomplete understanding of the molecular mechanisms responsible for myometrial activation from the quiescent pregnant state to the active contractile state during labor has hindered the development of effective therapies for preterm labor. Myometrial stretch has been implicated clinically in the initiation of labor and the etiology of preterm labor, but the molecular mechanisms involved in the human have not been determined. We investigated the mechanisms by which gestation-dependent stretch contributes to myometrial activation, by using human uterine samples from gynecologic hysterectomies and Cesarean sections. Here we demonstrate that the Ca requirement for activation of the contractile filaments in human myometrium increases with caldesmon protein content during gestation and that an increase in caldesmon phosphorylation can reverse this inhibitory effect during labor. By using phosphotyrosine screening and mass spectrometry of stretched human myometrial samples, we identify 3 stretch-activated focal adhesion proteins, FAK, p130Cas, and alpha actinin. FAK-Y397, which signals integrin engagement, is constitutively phosphorylated in term human myometrium whereas FAK-Y925, which signals downstream ERK activation, is phosphorylated during stretch. We have recently identified smooth muscle Archvillin (SmAV as an ERK regulator. A newly produced SmAV-specific antibody demonstrates gestation-specific increases in SmAV protein levels and stretch-specific increases in SmAV association with focal adhesion proteins. Thus, whereas increases in caldesmon levels suppress human myometrium contractility during pregnancy, stretch-dependent focal adhesion signaling, facilitated by the ERK activator SmAV, can contribute to myometrial activation. These results suggest that focal adhesion proteins may present new targets for drug discovery programs aimed at regulation of uterine contractility.

Toxic or dangerous substances present construction materials

International Nuclear Information System (INIS)

Campos Alvarado, A.

2003-01-01

The purpose of this investigation is the elaboration of a guide which could be used as a support and consultation concerning the topic of safety in the construction, specifically in the area of the use and managing of material and dangerous substances; considering the possible dangers to medium and long term that some of the common construction materials represent for the health. The gathered information is the result of the review of bibliographical material, the visits to public institutions at national level and to international offices which representation in our country, this way as a work of field and of study of the national market, among others. Besides important consult through the Internet checking many sites of interest with the finality of getting more updated information as possible, like that as the consultation to professionals and workers related to the construction area. (Author) [es

The Moral Challenge of Dangerous Climate Change: Values, Poverty, and Policy

DEFF Research Database (Denmark)

Crabtree, Andrew

2016-01-01

Book review of: The Moral Challenge of Dangerous Climate Change: Values, Poverty, and Policy by Darrel Moellendorf. New York: Cambridge University Press, 2014, pp. 263 (paperback), ISBN 978-1-107-67850-7......Book review of: The Moral Challenge of Dangerous Climate Change: Values, Poverty, and Policy by Darrel Moellendorf. New York: Cambridge University Press, 2014, pp. 263 (paperback), ISBN 978-1-107-67850-7...

Mitogen-activated protein kinase signaling in plants

DEFF Research Database (Denmark)

Rodriguez, Maria Cristina Suarez; Petersen, Morten; Mundy, John

2010-01-01

crossinhibition, feedback control, and scaffolding. Plant MAPK cascades regulate numerous processes, including stress and hormonal responses, innate immunity, and developmental programs. Genetic analyses have uncovered several predominant MAPK components shared by several of these processes including...... of substrate proteins, whose altered activities mediate a wide array of responses, including changes in gene expression. Cascades may share kinase components, but their signaling specificity is maintained by spaciotemporal constraints and dynamic protein-protein interactions and by mechanisms that include...

Activated factor X signaling via protease-activated receptor 2 suppresses pro-inflammatory cytokine production from LPS-stimulated myeloid cells.

LENUS (Irish Health Repository)

Gleeson, Eimear M

2013-07-19

Vitamin K-dependent proteases generated in response to vascular injury and infection enable fibrin clot formation, but also trigger distinct immuno-regulatory signaling pathways on myeloid cells. Factor Xa, a protease crucial for blood coagulation, also induces protease-activated receptor-dependent cell signaling. Factor Xa can bind both monocytes and macrophages, but whether factor Xa-dependent signaling stimulates or suppresses myeloid cell cytokine production in response to Toll-like receptor activation is not known. In this study, exposure to factor Xa significantly impaired pro-inflammatory cytokine production from lipopolysaccharide-treated peripheral blood mononuclear cells, THP-1 monocytic cells and murine macrophages. Furthermore, factor Xa inhibited nuclear factor-kappa B activation in THP-1 reporter cells, requiring phosphatidylinositide 3-kinase activity for its anti-inflammatory effect. Active-site blockade, γ-carboxyglutamic acid domain truncation and a peptide mimic of the factor Xa inter-epidermal growth factor-like region prevented factor Xa inhibition of lipopolysaccharide-induced tumour necrosis factor-α release. In addition, factor Xa anti-inflammatory activity was markedly attenuated by the presence of an antagonist of protease-activated receptor 2, but not protease-activated receptor 1. The key role of protease-activated receptor 2 in eliciting factor Xa-dependent anti-inflammatory signaling on macrophages was further underscored by the inability of factor Xa to mediate inhibition of tumour necrosis factor-α and interleukin-6 release from murine bone marrow-derived protease-activated receptor 2-deficient macrophages. We also show for the first time that, in addition to protease-activated receptor 2, factor Xa requires a receptor-associated protein-sensitive low-density lipoprotein receptor to inhibit lipopolysaccharide-induced cytokine production. Collectively, this study supports a novel function for factor Xa as an endogenous, receptor

Weak correlations between hemodynamic signals and ongoing neural activity during the resting state

Science.gov (United States)

Winder, Aaron T.; Echagarruga, Christina; Zhang, Qingguang; Drew, Patrick J.

2017-01-01

Spontaneous fluctuations in hemodynamic signals in the absence of a task or overt stimulation are used to infer neural activity. We tested this coupling by simultaneously measuring neural activity and changes in cerebral blood volume (CBV) in the somatosensory cortex of awake, head-fixed mice during periods of true rest, and during whisker stimulation and volitional whisking. Here we show that neurovascular coupling was similar across states, and large spontaneous CBV changes in the absence of sensory input were driven by volitional whisker and body movements. Hemodynamic signals during periods of rest were weakly correlated with neural activity. Spontaneous fluctuations in CBV and vessel diameter persisted when local neural spiking and glutamatergic input was blocked, and during blockade of noradrenergic receptors, suggesting a non-neuronal origin for spontaneous CBV fluctuations. Spontaneous hemodynamic signals reflect a combination of behavior, local neural activity, and putatively non-neural processes. PMID:29184204

Dangerous goods emergency response

International Nuclear Information System (INIS)

Price, K.

1991-01-01

This paper reports on a general overview of the State of Western Australia including: the legal framework of the Dangerous Goods and Emergency response management scenarios (which consist mainly of fuel products such as LP gas); particular problems unique to the Western Australian environment; what has been done to overcome those problems. Western Australia has an area of about two and a half million square kilometers. The demography of the State is such that the population is concentrated in the south-west corner of the State with isolated pockets, mainly associated with mineral development but also associated with agriculture, scattered throughout the State

Peroxisome proliferator-activated receptor β/δ (PPARβ/δ) activates promyogenic signaling pathways, thereby promoting myoblast differentiation

Energy Technology Data Exchange (ETDEWEB)

Lee, Sang-Jin; Go, Ga-Yeon; Yoo, Miran; Kim, Yong Kee [Research Center for Cell Fate Control, College of Pharmacy, Sookmyung Women' s University, Seoul 140-742 (Korea, Republic of); Seo, Dong-Wan [College of Pharmacy, Dankook University, Cheonan 330-714 (Korea, Republic of); Kang, Jong-Sun [Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Samsung Biomedical Research Institute, Suwon 440-746 (Korea, Republic of); Bae, Gyu-Un, E-mail: gbae@sookmyung.ac.kr [Research Center for Cell Fate Control, College of Pharmacy, Sookmyung Women' s University, Seoul 140-742 (Korea, Republic of)

2016-01-29

Peroxisome proliferator-activated receptor β/δ (PPARβ/δ) regulates postnatal myogenesis by alleviating myostatin activity, but the molecular mechanisms by which it regulates myogenesis are not fully understood. In this study, we investigate molecular mechanisms of PPARβ/δ in myoblast differentiation. C2C12 myoblasts treated with a PPARβ/δ agonist, GW0742 exhibit enhanced myotube formation and muscle-specific gene expression. GW0742 treatment dramatically activates promyogenic kinases, p38MAPK and Akt, in a dose-dependent manner. GW0742-stimulated myoblast differentiation is mediated by p38MAPK and Akt, since it failed to restore myoblast differentiation repressed by inhibition of p38MAPK and Akt. In addition, GW0742 treatment enhances MyoD-reporter activities. Consistently, overexpression of PPARβ/δ enhances myoblast differentiation accompanied by elevated activation of p38MAPK and Akt. Collectively, these results suggest that PPARβ/δ enhances myoblast differentiation through activation of promyogenic signaling pathways. - Highlights: • A PPARβ/δ agonist, GW0742 promotes myoblast differentiation. • GW0742 activates both p38MAPK and Akt activation in myogenic differentiation. • GW0742 enhances MyoD activity for myogenic differentiation. • Overexpression of PPARβ/δ enhances myoblast differentiation via activating promyogenic signaling pathways. • This is the first finding for agonistic mechanism of PPARβ/δ in myogenesis.

Peroxisome proliferator-activated receptor β/δ (PPARβ/δ) activates promyogenic signaling pathways, thereby promoting myoblast differentiation

International Nuclear Information System (INIS)

Lee, Sang-Jin; Go, Ga-Yeon; Yoo, Miran; Kim, Yong Kee; Seo, Dong-Wan; Kang, Jong-Sun; Bae, Gyu-Un

2016-01-01

Peroxisome proliferator-activated receptor β/δ (PPARβ/δ) regulates postnatal myogenesis by alleviating myostatin activity, but the molecular mechanisms by which it regulates myogenesis are not fully understood. In this study, we investigate molecular mechanisms of PPARβ/δ in myoblast differentiation. C2C12 myoblasts treated with a PPARβ/δ agonist, GW0742 exhibit enhanced myotube formation and muscle-specific gene expression. GW0742 treatment dramatically activates promyogenic kinases, p38MAPK and Akt, in a dose-dependent manner. GW0742-stimulated myoblast differentiation is mediated by p38MAPK and Akt, since it failed to restore myoblast differentiation repressed by inhibition of p38MAPK and Akt. In addition, GW0742 treatment enhances MyoD-reporter activities. Consistently, overexpression of PPARβ/δ enhances myoblast differentiation accompanied by elevated activation of p38MAPK and Akt. Collectively, these results suggest that PPARβ/δ enhances myoblast differentiation through activation of promyogenic signaling pathways. - Highlights: • A PPARβ/δ agonist, GW0742 promotes myoblast differentiation. • GW0742 activates both p38MAPK and Akt activation in myogenic differentiation. • GW0742 enhances MyoD activity for myogenic differentiation. • Overexpression of PPARβ/δ enhances myoblast differentiation via activating promyogenic signaling pathways. • This is the first finding for agonistic mechanism of PPARβ/δ in myogenesis.

Context Specificity of Stress-activated Mitogen-activated Protein (MAP) Kinase Signaling: The Story as Told by Caenorhabditis elegans*

Science.gov (United States)

Andrusiak, Matthew G.; Jin, Yishi

2016-01-01

Stress-associated p38 and JNK mitogen-activated protein (MAP) kinase signaling cascades trigger specific cellular responses and are involved in multiple disease states. At the root of MAP kinase signaling complexity is the differential use of common components on a context-specific basis. The roundworm Caenorhabditis elegans was developed as a system to study genes required for development and nervous system function. The powerful genetics of C. elegans in combination with molecular and cellular dissections has led to a greater understanding of how p38 and JNK signaling affects many biological processes under normal and stress conditions. This review focuses on the studies revealing context specificity of different stress-activated MAPK components in C. elegans. PMID:26907690

Hanford facility dangerous waste permit application, 325 hazardous waste treatment units. Revision 1

International Nuclear Information System (INIS)

1997-07-01

This report contains the Hanford Facility Dangerous Waste Permit Application for the 325 Hazardous Waste Treatment Units (325 HWTUs) which consist of the Shielded Analytical Laboratory, the 325 Building, and the 325 Collection/Loadout Station Tank. The 325 HWTUs receive, store, and treat dangerous waste generated by Hanford Facility programs. Routine dangerous and/or mixed waste treatment that will be conducted in the 325 HWTUs will include pH adjustment, ion exchange, carbon absorption, oxidation, reduction, waste concentration by evaporation, precipitation, filtration, solvent extraction, solids washing, phase separation, catalytic destruction, and solidification/stabilization

Hanford facility dangerous waste permit application, 325 hazardous waste treatment units. Revision 1

Energy Technology Data Exchange (ETDEWEB)

NONE

1997-07-01

This report contains the Hanford Facility Dangerous Waste Permit Application for the 325 Hazardous Waste Treatment Units (325 HWTUs) which consist of the Shielded Analytical Laboratory, the 325 Building, and the 325 Collection/Loadout Station Tank. The 325 HWTUs receive, store, and treat dangerous waste generated by Hanford Facility programs. Routine dangerous and/or mixed waste treatment that will be conducted in the 325 HWTUs will include pH adjustment, ion exchange, carbon absorption, oxidation, reduction, waste concentration by evaporation, precipitation, filtration, solvent extraction, solids washing, phase separation, catalytic destruction, and solidification/stabilization.

The wind energy in danger in France

International Nuclear Information System (INIS)

2005-03-01

The law project of march 2005, concerning the energy policy in France is dangerous for the wind power development. The new regulation favor the big installations in order to protect the environment. In fact this decision will limit the wind turbines installations. (A.L.B.)

Awareness of eSafety and Potential Online Dangers among Children and Teenagers

Science.gov (United States)

Zilka, Gila Cohen

2017-01-01

Aim/Purpose: Awareness of eSafety and potential online dangers for children and teenagers. Background: The study examined eSafety among children and teenagers from their own perspectives, through evaluations of their awareness level of eSafety and of potential online dangers. Methodology: This is a mixed-method study with both quantitative and…

Extracellular signal-regulated protein kinases 1 and 2 activation by addictive drugs: a signal toward pathological adaptation.

Science.gov (United States)

Pascoli, Vincent; Cahill, Emma; Bellivier, Frank; Caboche, Jocelyne; Vanhoutte, Peter

2014-12-15

Addiction is a chronic and relapsing psychiatric disorder that is thought to occur in vulnerable individuals. Synaptic plasticity evoked by drugs of abuse in the so-called neuronal circuits of reward has been proposed to underlie behavioral adaptations that characterize addiction. By increasing dopamine in the striatum, addictive drugs alter the balance of dopamine and glutamate signals converging onto striatal medium-sized spiny neurons (MSNs) and activate intracellular events involved in long-term behavioral alterations. Our laboratory contributed to the identification of salient molecular changes induced by administration of addictive drugs to rodents. We pioneered the observation that a common feature of addictive drugs is to activate, by a double tyrosine/threonine phosphorylation, the extracellular signal-regulated kinases 1 and 2 (ERK1/2) in the striatum, which control a plethora of substrates, some of them being critically involved in cocaine-mediated molecular and behavioral adaptations. Herein, we review how the interplay between dopamine and glutamate signaling controls cocaine-induced ERK1/2 activation in MSNs. We emphasize the key role of N-methyl-D-aspartate receptor potentiation by D1 receptor to trigger ERK1/2 activation and its subsequent nuclear translocation where it modulates both epigenetic and genetic processes engaged by cocaine. We discuss how cocaine-induced long-term synaptic and structural plasticity of MSNs, as well as behavioral adaptations, are influenced by ERK1/2-controlled targets. We conclude that a better knowledge of molecular mechanisms underlying ERK1/2 activation by drugs of abuse and/or its role in long-term neuronal plasticity in the striatum may provide a new route for therapeutic treatment in addiction. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

River Protection Project (RPP) Dangerous Waste Training Plan

Energy Technology Data Exchange (ETDEWEB)

POHTO, R.E.

2000-03-09

This supporting document contains the training plan for dangerous waste management at River Protection Project TSD Units. This document outlines the dangerous waste training program developed and implemented for all Treatment, Storage, and Disposal (TSD) Units operated by River Protection Project (RPP) in the Hanford 200 East, 200 West and 600 Areas and the <90 Day Accumulation Area at 209E. Operating TSD Units managed by RPP are: the Double-Shell Tank (DST) System, 204-AR Waste Unloading Facility, Grout, and the Single-Shell Tank (SST) System. The program is designed in compliance with the requirements of Washington Administrative Code (WAC) 173-303-330 and Title 40 Code of Federal Regulations (CFR) 265.16 for the development of a written dangerous waste training program and the Hanford Facility Permit. Training requirements were determined by an assessment of employee duties and responsibilities. The RPP training program is designed to prepare employees to operate and maintain the Tank Farms in a safe, effective, efficient, and environmentally sound manner. In addition to preparing employees to operate and maintain the Tank Farms under normal conditions, the training program ensures that employees are prepared to respond in a prompt and effective manner should abnormal or emergency conditions occur. Emergency response training is consistent with emergency responses outlined in the following Building Emergency Plans: HNF-IP-0263-TF and HNF-=IP-0263-209E.

River Protection Project (RPP) Dangerous Waste Training Plan

International Nuclear Information System (INIS)

POHTO, R.E.

2000-01-01

This supporting document contains the training plan for dangerous waste management at River Protection Project TSD Units. This document outlines the dangerous waste training program developed and implemented for all Treatment, Storage, and Disposal (TSD) Units operated by River Protection Project (RPP) in the Hanford 200 East, 200 West and 600 Areas and the <90 Day Accumulation Area at 209E. Operating TSD Units managed by RPP are: the Double-Shell Tank (DST) System, 204-AR Waste Unloading Facility, Grout, and the Single-Shell Tank (SST) System. The program is designed in compliance with the requirements of Washington Administrative Code (WAC) 173-303-330 and Title 40 Code of Federal Regulations (CFR) 265.16 for the development of a written dangerous waste training program and the Hanford Facility Permit. Training requirements were determined by an assessment of employee duties and responsibilities. The RPP training program is designed to prepare employees to operate and maintain the Tank Farms in a safe, effective, efficient, and environmentally sound manner. In addition to preparing employees to operate and maintain the Tank Farms under normal conditions, the training program ensures that employees are prepared to respond in a prompt and effective manner should abnormal or emergency conditions occur. Emergency response training is consistent with emergency responses outlined in the following Building Emergency Plans: HNF-IP-0263-TF and HNF-=IP-0263-209E

How common is within-plant signaling via volatiles?

Science.gov (United States)

Li, Tao; Blande, James D

2017-08-03

Many plants respond to herbivory by releasing a complex blend of volatiles that may differ from that emitted by intact counterparts. These herbivore-induced plant volatiles (HIPV) mediate many interactions among plants and their community members, including alerting undamaged leaves of the attacked or neighboring plants to impending danger. It has been postulated that HIPVs evolved for within-plant signaling and that other organisms subsequently evolved to use them. However, only 7 studies have reported HIPV-mediated within-plant signaling, most conducted in the laboratory or greenhouse. This leaves open the ecological relevance and evolutionary underpinning of the phenomenon. We recently observed within-plant signaling in hybrid aspen under laboratory and field conditions. Greenhouse experiments showed that HIPVs mediated the process. While our study adds an aspen hybrid to the list of plants in which within-plant signaling has been demonstrated, we lack understanding of how common the process is and whether plants obtain fitness benefits.

Diffusion-weighted magnetic resonance imaging reflects activation of signal transducer and activator of transcription 3 during focal cerebral ischemia/reperfusion

Directory of Open Access Journals (Sweden)

Wen-juan Wu

2017-01-01

Full Text Available Signal transducer and activator of transcription (STAT is a unique protein family that binds to DNA, coupled with tyrosine phosphorylation signaling pathways, acting as a transcriptional regulator to mediate a variety of biological effects. Cerebral ischemia and reperfusion can activate STATs signaling pathway, but no studies have confirmed whether STAT activation can be verified by diffusion-weighted magnetic resonance imaging (DWI in rats after cerebral ischemia/reperfusion. Here, we established a rat model of focal cerebral ischemia injury using the modified Longa method. DWI revealed hyperintensity in parts of the left hemisphere before reperfusion and a low apparent diffusion coefficient. STAT3 protein expression showed no significant change after reperfusion, but phosphorylated STAT3 expression began to increase after 30 minutes of reperfusion and peaked at 24 hours. Pearson correlation analysis showed that STAT3 activation was correlated positively with the relative apparent diffusion coefficient and negatively with the DWI abnormal signal area. These results indicate that DWI is a reliable representation of the infarct area and reflects STAT phosphorylation in rat brain following focal cerebral ischemia/reperfusion.

Hanford Waste Vitrification Plant Dangerous Waste Permit Application

International Nuclear Information System (INIS)

1991-10-01

The Hanford Facility currently stores mixed waste, resulting from various processing operations, in underground storage tanks. The Hanford Waste Vitrification Plant will be constructed and operated to process the high-activity fraction of mixed waste stored in these underground tanks. The Hanford Waste Vitrification Plant will solidify pretreated tank waste into a glass product that will be packaged for disposal in a national repository. This Vitrification Plant Dangerous Waste Permit Application, Revision 2, consists of both a Part A and a Part B permit application. An explanation of the Part A revisions, including Revision 4 submitted with this application, is provided at the beginning of the Part A section. The Part B consists of 15 chapters addressing the organization and content of the Part B Checklist prepared by the Washington State Department of Ecology (Ecology 1987)

The advisory list for selvclassification of dangerous substances

DEFF Research Database (Denmark)

Niemelä, Jay Russell; Wedebye, Eva Bay; Nikolov, Nikolai Georgiev

All chemical substances marketed in the EU must be classified and labelled according to the regulation on classification and labelling of dangerous substances (7). Substances with harmonised classifications adopted in the EU are to be found on the List of harmonised classification and labelling...... this issue, the Danish Environmental Protection Agency published the Advisory Self-classification List /5/. This report describes the updating of this list. The Advisory Self-Classification list is created by the use of (Q)SARs ((Quantitative) Structure-Activity Relationships) to predict the effects...... Skin sensitisation The updated advisory list is available as an Excel file for download from DK-EPA's website and as an online searchable database. This includes the 23,922 chemicals with new advisory classifications resulting from this project, making in all, a total of 30,179 chemicals with advisory...

Mitogen-activated protein kinase and abscisic acid signal transduction

NARCIS (Netherlands)

Heimovaara-Dijkstra, S.; Testerink, C.; Wang, M.

1998-01-01

The phytohormone abscisic acid (ABA) is a classical plant hormone, responsible for regulation of abscission, diverse aspects of plant and seed development, stress responses and germination. It was found that ABA signal transduction in plants can involve the activity of type 2C-phosphatases (PP2C),

Noncanonical ATM Activation and Signaling in Response to Transcription-Blocking DNA Damage.

Science.gov (United States)

Marteijn, Jurgen A; Vermeulen, Wim; Tresini, Maria

2017-01-01

Environmental genotoxins and metabolic byproducts generate DNA lesions that can cause genomic instability and disrupt tissue homeostasis. To ensure genomic integrity, cells employ mechanisms that convert signals generated by stochastic DNA damage into organized responses, including activation of repair systems, cell cycle checkpoints, and apoptotic mechanisms. DNA damage response (DDR) signaling pathways coordinate these responses and determine cellular fates in part, by transducing signals that modulate RNA metabolism. One of the master DDR coordinators, the Ataxia Telangiectasia Mutated (ATM) kinase, has a fundamental role in mediating DNA damage-induced changes in mRNA synthesis. ATM acts by modulating a variety of RNA metabolic pathways including nascent RNA splicing, a process catalyzed by the spliceosome. Interestingly, ATM and the spliceosome influence each other's activity in a reciprocal manner by a pathway that initiates when transcribing RNA polymerase II (RNAPII) encounters DNA lesions that prohibit forward translocation. In response to stalling of RNAPII assembly of late-stage spliceosomes is disrupted resulting in increased splicing factor mobility. Displacement of spliceosomes from lesion-arrested RNA polymerases facilitates formation of R-loops between the nascent RNA and DNA adjacent to the transcription bubble. R-loops signal for noncanonical ATM activation which in quiescent cells occurs in absence of detectable dsDNA breaks. In turn, activated ATM signals to regulate spliceosome dynamics and AS genome wide.This chapter describes the use of fluorescence microscopy methods that can be used to evaluate noncanonical ATM activation by transcription-blocking DNA damage. First, we present an immunofluorescence-detection method that can be used to evaluate ATM activation by autophosphorylation, in fixed cells. Second, we present a protocol for Fluorescence Recovery After Photobleaching (FRAP) of GFP-tagged splicing factors, a highly sensitive and

Hair follicle stem cell proliferation, Akt and Wnt signaling activation in TPA-induced hair regeneration.

Science.gov (United States)

Qiu, Weiming; Lei, Mingxing; Zhou, Ling; Bai, Xiufeng; Lai, Xiangdong; Yu, Yu; Yang, Tian; Lian, Xiaohua

2017-06-01

Regeneration of hair follicles relies on activation of hair follicle stem cells during telogen to anagen transition process in hair cycle. This process is rigorously controlled by intrinsic and environmental factors. 12-o-tetradecanoylphorbol-13-acetate (TPA), a tumor promoter, accelerates reentry of hair follicles into anagen phase. However, it is unclear that how TPA promotes the hair regeneration. In the present study, we topically applied TPA onto the dorsal skin of 2-month-old C57BL/6 female mice to examine the activity of hair follicle stem cells and alteration of signaling pathways during hair regeneration. We found that refractory telogen hair follicles entered anagen prematurely after TPA treatment, with the enhanced proliferation of CD34-positive hair follicle stem cells. Meanwhile, we observed Akt signaling was activated in epidermis, hair infundibulum, bulge and hair bulb, and Wnt signaling was also activated after hair follicle stem cells proliferation. Importantly, after overexpression of DKK1, a specific Wnt signaling inhibitor, the accelerated reentry of hair follicles into anagen induced by TPA was abolished. Our data indicated that TPA-induced hair follicle regeneration is associated with activation of Akt and Wnt/β-catenin signaling.

Hydrogen peroxide induces activation of insulin signaling pathway via AMP-dependent kinase in podocytes

International Nuclear Information System (INIS)

Piwkowska, Agnieszka; Rogacka, Dorota; Angielski, Stefan; Jankowski, Maciej

2012-01-01

Highlights: ► H 2 O 2 activates the insulin signaling pathway and glucose uptake in podocytes. ► H 2 O 2 induces time-dependent changes in AMPK phosphorylation. ► H 2 O 2 enhances insulin signaling pathways via AMPK activation. ► H 2 O 2 stimulation of glucose uptake is AMPK-dependent. -- Abstract: Podocytes are cells that form the glomerular filtration barrier in the kidney. Insulin signaling in podocytes is critical for normal kidney function. Insulin signaling is regulated by oxidative stress and intracellular energy levels. We cultured rat podocytes to investigate the effects of hydrogen peroxide (H 2 O 2 ) on the phosphorylation of proximal and distal elements of insulin signaling. We also investigated H 2 O 2 -induced intracellular changes in the distribution of protein kinase B (Akt). Western blots showed that H 2 O 2 (100 μM) induced rapid, transient phosphorylation of the insulin receptor (IR), the IR substrate-1 (IRS1), and Akt with peak activities at 5 min (Δ 183%, P 2 O 2 >. Furthermore, H 2 O 2 inhibited phosphorylation of the phosphatase and tensin homologue (PTEN; peak activity at 10 min; Δ −32%, P 2 O 2 on IR phosphorylation by about 40% (from 2.07 ± 0.28 to 1.28 ± 0.12, P 2 O 2 increased glucose uptake in podocytes (from 0.88 ± 0.04 to 1.29 ± 0.12 nmol/min/mg protein, P 2 O 2 activated the insulin signaling pathway and glucose uptake via AMPK in cultured rat podocytes. This signaling may play a potential role in the prevention of insulin resistance under conditions associated with oxidative stress.

The chemical industry - a danger to nuclear power plants

International Nuclear Information System (INIS)

Voigtsberger, P.

1976-01-01

Nuclear power stations could contaminate large areas with radioactivity when destroyed by strong external influences. In Germany, authorities try to cope with this danger firstly by making certain demands on the strength of the reactor shell and secondly by imposing strict safety regulations on dangerous industrial plants in the surroundings of the reactor. In the case of chemical industry, this means: If a chemical plant and a nuclear reactor lie closely together, special stress is given to explosion pretection measures in the form of primary explosion protection, e.g. strong sealing of inflammable gases and liquids handled in the immediate neighbourhood of the reactor. (orig.) [de

Inherent Dangers in Orogenital Sex During Pregnancy

African Journals Online (AJOL)

Coitus and cunnilingus during pregnancy are generally safe; whereas orogenital sex involving vaginal air insufflations can be very dangerous, causing even the death of the women. We carried out a search of case reports and reviews concerning air embolism during pregnancy due to orogenital sex. Physicians ...

The dangers of long-term catheter drainage.

Science.gov (United States)

Lowthian, P

There are many dangers associated with long-term urinary bladder drainage by catheter. For various reasons, the choice of catheter is important, and its initial insertion can be particularly hazardous. All catheterizations should, however, be safer when there is some urine (or other fluid) in the bladder. The appropriate choice of drainage system attached to the catheter can delay bacterial invasion of the bladder. Great care is needed to prevent blockage of the system, particularly when bacteriuria is present. Recent evidence indicates that some bacteria encourage the development of encrustations, so that, in some circumstances, catheters may become blocked within 24 hours. This, together with other considerations, strongly suggests that indwelling catheters should be changed at intervals of not more than 5 days. The practical implications of this are considered, as are the benefits that may accrue. Accidental catheter traction is another danger, and some possible methods of avoiding this are discussed. Finally, the need for a new kind of drainage-bag support is highlighted.

Neuronal MHC Class I Expression Is Regulated by Activity Driven Calcium Signaling.

Directory of Open Access Journals (Sweden)

Dan Lv

Full Text Available MHC class I (MHC-I molecules are important components of the immune system. Recently MHC-I have been reported to also play important roles in brain development and synaptic plasticity. In this study, we examine the molecular mechanism(s underlying activity-dependent MHC-I expression using hippocampal neurons. Here we report that neuronal expression level of MHC-I is dynamically regulated during hippocampal development after birth in vivo. Kainic acid (KA treatment significantly increases the expression of MHC-I in cultured hippocampal neurons in vitro, suggesting that MHC-I expression is regulated by neuronal activity. In addition, KA stimulation decreased the expression of pre- and post-synaptic proteins. This down-regulation is prevented by addition of an MHC-I antibody to KA treated neurons. Further studies demonstrate that calcium-dependent protein kinase C (PKC is important in relaying KA simulation activation signals to up-regulated MHC-I expression. This signaling cascade relies on activation of the MAPK pathway, which leads to increased phosphorylation of CREB and NF-κB p65 while also enhancing the expression of IRF-1. Together, these results suggest that expression of MHC-I in hippocampal neurons is driven by Ca2+ regulated activation of the MAPK signaling transduction cascade.

Stromal COX-2 signaling activated by deoxycholic acid mediates proliferation and invasiveness of colorectal epithelial cancer cells

International Nuclear Information System (INIS)

Zhu, Yingting; Zhu, Min; Lance, Peter

2012-01-01

Highlights: ► Human colonic cancer associated fibroblasts are major sources of COX-2 and PGE 2 . ► The fibroblasts interact with human colonic epithelial cancer cells. ► Activation of COX-2 signaling in the fibroblasts affects behavior of the epithelia. ► Protein Kinase C controls the activation of COX-2 signaling. -- Abstract: COX-2 is a major regulator implicated in colonic cancer. However, how COX-2 signaling affects colonic carcinogenesis at cellular level is not clear. In this article, we investigated whether activation of COX-2 signaling by deoxycholic acid (DCA) in primary human normal and cancer associated fibroblasts play a significant role in regulation of proliferation and invasiveness of colonic epithelial cancer cells. Our results demonstrated while COX-2 signaling can be activated by DCA in both normal and cancer associated fibroblasts, the level of activation of COX-2 signaling is significantly greater in cancer associated fibroblasts than that in normal fibroblasts. In addition, we discovered that the proliferative and invasive potential of colonic epithelial cancer cells were much greater when the cells were co-cultured with cancer associated fibroblasts pre-treated with DCA than with normal fibroblasts pre-treated with DCA. Moreover, COX-2 siRNA attenuated the proliferative and invasive effect of both normal and cancer associate fibroblasts pre-treated with DCA on the colonic cancer cells. Further studies indicated that the activation of COX-2 signaling by DCA is through protein kinase C signaling. We speculate that activation of COX-2 signaling especially in cancer associated fibroblasts promotes progression of colonic cancer.

Cyclic AMP signaling restricts activation and promotes maturation and antioxidant defenses in astrocytes.

Science.gov (United States)

Paco, Sonia; Hummel, Manuela; Plá, Virginia; Sumoy, Lauro; Aguado, Fernando

2016-04-23

cAMP signaling produces dramatic changes in astrocyte morphology and physiology. However, its involvement in phenotype acquisition and the transcriptionally mediated mechanisms of action are largely unknown. Here we analyzed the global transcriptome of cultured astroglial cells incubated with activators of cAMP pathways. A bulk of astroglial transcripts, 6221 annotated genes, were differentially regulated by cAMP signaling. cAMP analogs strongly upregulated genes involved in typical functions of mature astrocytes, such as homeostatic control, metabolic and structural support to neurons, antioxidant defense and communication, whereas they downregulated a considerable number of proliferating and immaturity-related transcripts. Moreover, numerous genes typically activated in reactive cells, such as scar components and immunological mediators, were repressed by cAMP. GSEA analysis contrasting gene expression profiles with transcriptome signatures of acutely isolated astrocytes and in situ evaluation of protein levels in these cells showed that cAMP signaling conferred mature and in vivo-like transcriptional features to cultured astrocytes. These results indicate that cAMP signaling is a key pathway promoting astrocyte maturation and restricting their developmental and activation features. Therefore, a positive modulation of cAMP signaling may promote the normal state of differentiated astrocytes and favor the protection and function of neuronal networks.

A Discrete Dynamical System Approach to Pathway Activation Profiles of Signaling Cascades.

Science.gov (United States)

Catozzi, S; Sepulchre, J-A

2017-08-01

In living organisms, cascades of covalent modification cycles are one of the major intracellular signaling mechanisms, allowing to transduce physical or chemical stimuli of the external world into variations of activated biochemical species within the cell. In this paper, we develop a novel method to study the stimulus-response of signaling cascades and overall the concept of pathway activation profile which is, for a given stimulus, the sequence of activated proteins at each tier of the cascade. Our approach is based on a correspondence that we establish between the stationary states of a cascade and pieces of orbits of a 2D discrete dynamical system. The study of its possible phase portraits in function of the biochemical parameters, and in particular of the contraction/expansion properties around the fixed points of this discrete map, as well as their bifurcations, yields a classification of the cascade tiers into three main types, whose biological impact within a signaling network is examined. In particular, our approach enables to discuss quantitatively the notion of cascade amplification/attenuation from this new perspective. The method allows also to study the interplay between forward and "retroactive" signaling, i.e., the upstream influence of an inhibiting drug bound to the last tier of the cascade.

Recommendations on the transport of dangerous goods. Model regulations. 11. revised ed.

International Nuclear Information System (INIS)

1999-01-01

The Recommendations on the Transport of Dangerous Goods are addressed to governments and to the international organizations concerned with the regulation of the transport of dangerous goods. They have been prepared by the United Nations Economic and Social Council's Committee of Experts on the Transport of Dangerous Goods, and they were first published in 1956 (ST/ECA/43-E/CN.2/170). Pursuant to Resolution 645 G (XXIII) of 26 April 1957 of the Economic and Social Council and subsequent resolutions, they have been regularly amended and updated at succeeding sessions of the Committee of Experts. At its eighteenth session (28 November-7 December 1994), the Committee of Experts considered that reformatting the Recommendations on the Transport of Dangerous Goods into Model Regulations that could be directly integrated into all modal national and international regulations would enhance harmonization, facilitate regular up-dating of all legal instruments concerned, and result in overall considerable resource savings for the Governments of the Member States, the United Nations, the specialized agencies and other international organizations. At its nineteenth session (2-10 December 1996), the Committee adopted a first version of the Model Regulations on the Transport of Dangerous Goods, which was annexed to the tenth revised edition of the Recommendations on the Transport of Dangerous Goods. At its twentieth session (7-16 December 1998), the Committee adopted various amendments to the Model Regulations and new provisions including, in particular, packing instructions for individual substances and articles and additional provisions for the transport of radioactive material. The additional provisions concerning the transport of radioactive material were developed in close cooperation with the International Atomic Energy Agency (IAEA) and are based on the 1996 Edition of the IAEA Regulations for the Safe Transport of Radioactive Material which have been reformatted so as to be

Monitoring Dangerous Goods in Container Yard Using the Internet of Things

Directory of Open Access Journals (Sweden)

Lianhong Ding

2016-01-01

Full Text Available The Internet of Things (IoT, a network of objects, has been regarded as the next revolution for the global information industry after the Internet. With IoT, many intelligent applications can be accomplished or improved. This paper presents a framework for dangerous goods management in container yard using IoT technology. The framework consists of three layers: perceptual layer, transport layer, and application layer. It offers an infrastructure for management and data analysis and utilization. According to the features of dangerous goods, the framework can be enhanced for container information forecast, container gate-in and gate-out management, environment parameters monitoring, and fire control as well. In order to verify our method, a prototype system is developed, which shows good performance. With our method, safe operation of dangerous goods in container yard can be accomplished.

Context Specificity of Stress-activated Mitogen-activated Protein (MAP) Kinase Signaling: The Story as Told by Caenorhabditis elegans.

Science.gov (United States)

Andrusiak, Matthew G; Jin, Yishi

2016-04-08

Stress-associated p38 and JNK mitogen-activated protein (MAP) kinase signaling cascades trigger specific cellular responses and are involved in multiple disease states. At the root of MAP kinase signaling complexity is the differential use of common components on a context-specific basis. The roundwormCaenorhabditis eleganswas developed as a system to study genes required for development and nervous system function. The powerful genetics ofC. elegansin combination with molecular and cellular dissections has led to a greater understanding of how p38 and JNK signaling affects many biological processes under normal and stress conditions. This review focuses on the studies revealing context specificity of different stress-activated MAPK components inC. elegans. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

[Insight and psychiatric dangerousness: A review of the literature].

Science.gov (United States)

Bonnet, S; Lacambre, M; Schandrin, A; Capdevielle, D; Courtet, P

2017-04-01

Violence committed by individuals with severe mental illness has become an increasing focus of concern among clinicians, policy makers, and the general public, often as the result of tragic events. Research has shown in the past two decades an increased risk of violence among patients with mental disorder. Nevertheless, of those suffering from mental illness, perpetrators of other directed violence form a minority subgroup. The means by which there is this association between mental illness and violence has remained controversial. Factors such as positive psychotic symptoms, medication non-adherence, alcohol or psychoactive substance abuse and antisocial personality were found to be predictive of violence. Overall, literature provides support to the assertion that violent behavior of mentally ill patients is a heterogeneous phenomenon that is driven by multiple inter-related and independent factors. Furthermore, psychiatrists are often asked to predict an individual's future dangerousness, in a medical or a legal context. In the process of risk assessment of dangerousness, more focus has been placed on dynamic risk factor. In this context, lack of insight has established itself both as a part of violence risk models and as a clinical item in structured approaches to measure dangerousness. However, few studies have tested these associations. The main purpose of this paper is to review the literature concerning the relationship between insight and dangerousness and discuss the contributions of the insight in the assessment of dangerousness in patients with mental illness. We included twenty studies that evaluated the association between insight and variable such as physical or verbal violence, aggressiveness, hostility or sexual aggression. According to the findings of this review, the strength and specific nature of this relationship remain unclear due to considerable methodological and conceptual shortcomings, including heterogeneity in the definition and

Transport of dangerous goods through road tunnels

DEFF Research Database (Denmark)

Jørgensen, N O; Lacroix, Didier; Amundsen, F.H.

1999-01-01

A paper which describes the work of an OECD research group. The group has suggested a grouping of dangerous materials, a quantitative risk assessment model and a decision support model which should allow tunnel operators to determine if a given material should be allowed throug a given tunnel...

Artifact suppression and analysis of brain activities with electroencephalography signals.

Science.gov (United States)

Rashed-Al-Mahfuz, Md; Islam, Md Rabiul; Hirose, Keikichi; Molla, Md Khademul Islam

2013-06-05

Brain-computer interface is a communication system that connects the brain with computer (or other devices) but is not dependent on the normal output of the brain (i.e., peripheral nerve and muscle). Electro-oculogram is a dominant artifact which has a significant negative influence on further analysis of real electroencephalography data. This paper presented a data adaptive technique for artifact suppression and brain wave extraction from electroencephalography signals to detect regional brain activities. Empirical mode decomposition based adaptive thresholding approach was employed here to suppress the electro-oculogram artifact. Fractional Gaussian noise was used to determine the threshold level derived from the analysis data without any training. The purified electroencephalography signal was composed of the brain waves also called rhythmic components which represent the brain activities. The rhythmic components were extracted from each electroencephalography channel using adaptive wiener filter with the original scale. The regional brain activities were mapped on the basis of the spatial distribution of rhythmic components, and the results showed that different regions of the brain are activated in response to different stimuli. This research analyzed the activities of a single rhythmic component, alpha with respect to different motor imaginations. The experimental results showed that the proposed method is very efficient in artifact suppression and identifying individual motor imagery based on the activities of alpha component.

Stromal COX-2 signaling activated by deoxycholic acid mediates proliferation and invasiveness of colorectal epithelial cancer cells

Energy Technology Data Exchange (ETDEWEB)

Zhu, Yingting, E-mail: yitizhu@yahoo.com [Arizona Cancer Center, The University of Arizona, Tucson, AZ 85724 (United States); Tissue Tech Inc., Miami, FL 33173 (United States); Zhu, Min; Lance, Peter [Arizona Cancer Center, The University of Arizona, Tucson, AZ 85724 (United States)

2012-08-31

Highlights: Black-Right-Pointing-Pointer Human colonic cancer associated fibroblasts are major sources of COX-2 and PGE{sub 2}. Black-Right-Pointing-Pointer The fibroblasts interact with human colonic epithelial cancer cells. Black-Right-Pointing-Pointer Activation of COX-2 signaling in the fibroblasts affects behavior of the epithelia. Black-Right-Pointing-Pointer Protein Kinase C controls the activation of COX-2 signaling. -- Abstract: COX-2 is a major regulator implicated in colonic cancer. However, how COX-2 signaling affects colonic carcinogenesis at cellular level is not clear. In this article, we investigated whether activation of COX-2 signaling by deoxycholic acid (DCA) in primary human normal and cancer associated fibroblasts play a significant role in regulation of proliferation and invasiveness of colonic epithelial cancer cells. Our results demonstrated while COX-2 signaling can be activated by DCA in both normal and cancer associated fibroblasts, the level of activation of COX-2 signaling is significantly greater in cancer associated fibroblasts than that in normal fibroblasts. In addition, we discovered that the proliferative and invasive potential of colonic epithelial cancer cells were much greater when the cells were co-cultured with cancer associated fibroblasts pre-treated with DCA than with normal fibroblasts pre-treated with DCA. Moreover, COX-2 siRNA attenuated the proliferative and invasive effect of both normal and cancer associate fibroblasts pre-treated with DCA on the colonic cancer cells. Further studies indicated that the activation of COX-2 signaling by DCA is through protein kinase C signaling. We speculate that activation of COX-2 signaling especially in cancer associated fibroblasts promotes progression of colonic cancer.

Relations of Parenting to Adolescent Externalizing and Internalizing Distress Moderated by Perception of Neighborhood Danger.

Science.gov (United States)

Goldner, Jonathan S; Quimby, Dakari; Richards, Maryse H; Zakaryan, Arie; Miller, Steve; Dickson, Daniel; Chilson, Jessica

2016-01-01

Parental monitoring and warmth have traditionally been studied in the context of White, middle-class families. This article explores optimal levels of these parenting behaviors in preventing adolescent psychopathology in impoverished, urban high-crime areas while accounting for child perceptions of neighborhood danger. In this study, data were collected longitudinally at 2 time points 1 year apart from a sample of 254 African American young adolescents (T1: M age = 12.6 years, 41% male) and their parents. Parental monitoring and warmth, child perception of neighborhood danger, and child internalizing and externalizing behaviors were measured using questionnaires. Child internalizing behaviors were also measured using a time sampling technique capturing in vivo accounts of daily distress. Findings indicated associations between parental monitoring and children's externalizing behaviors along with linear and quadratic associations between parental monitoring and internalizing behaviors. Monitoring and warmth were differentially related to symptoms depending on neighborhood danger level. When children perceived less danger, more monitoring related to less externalizing. When children perceived more danger, more warmth related to less internalizing. In addition, adolescents' perceptions of neighborhood danger emerged as equally strong as monitoring and warmth in predicting symptoms. This study underscores the influence of carefully considering parenting approaches and which techniques optimally prevent adolescents' externalizing, as well as prevent internalizing difficulties. It also highlights how context affects mental health, specifically how perceptions of danger negatively influence adolescents' psychopathology, emphasizing the importance of initiatives to reduce violence in communities.

Active voltammetric microsensors with neural signal processing.

Energy Technology Data Exchange (ETDEWEB)

Vogt, M. C.

1998-12-11

Many industrial and environmental processes, including bioremediation, would benefit from the feedback and control information provided by a local multi-analyte chemical sensor. For most processes, such a sensor would need to be rugged enough to be placed in situ for long-term remote monitoring, and inexpensive enough to be fielded in useful numbers. The multi-analyte capability is difficult to obtain from common passive sensors, but can be provided by an active device that produces a spectrum-type response. Such new active gas microsensor technology has been developed at Argonne National Laboratory. The technology couples an electrocatalytic ceramic-metallic (cermet) microsensor with a voltammetric measurement technique and advanced neural signal processing. It has been demonstrated to be flexible, rugged, and very economical to produce and deploy. Both narrow interest detectors and wide spectrum instruments have been developed around this technology. Much of this technology's strength lies in the active measurement technique employed. The technique involves applying voltammetry to a miniature electrocatalytic cell to produce unique chemical ''signatures'' from the analytes. These signatures are processed with neural pattern recognition algorithms to identify and quantify the components in the analyte. The neural signal processing allows for innovative sampling and analysis strategies to be employed with the microsensor. In most situations, the whole response signature from the voltammogram can be used to identify, classify, and quantify an analyte, without dissecting it into component parts. This allows an instrument to be calibrated once for a specific gas or mixture of gases by simple exposure to a multi-component standard rather than by a series of individual gases. The sampled unknown analytes can vary in composition or in concentration, the calibration, sensing, and processing methods of these active voltammetric microsensors can

Active voltammetric microsensors with neural signal processing

Science.gov (United States)

Vogt, Michael C.; Skubal, Laura R.

1999-02-01

Many industrial and environmental processes, including bioremediation, would benefit from the feedback and control information provided by a local multi-analyte chemical sensor. For most processes, such a sensor would need to be rugged enough to be placed in situ for long-term remote monitoring, and inexpensive enough to be fielded in useful numbers. The multi-analyte capability is difficult to obtain from common passive sensors, but can be provided by an active device that produces a spectrum-type response. Such new active gas microsensor technology has been developed at Argonne National Laboratory. The technology couples an electrocatalytic ceramic-metallic (cermet) microsensor with a voltammetric measurement technique and advanced neural signal processing. It has been demonstrated to be flexible, rugged, and very economical to produce and deploy. Both narrow interest detectors and wide spectrum instruments have been developed around this technology. Much of this technology's strength lies in the active measurement technique employed. The technique involves applying voltammetry to a miniature electrocatalytic cell to produce unique chemical 'signatures' from the analytes. These signatures are processed with neural pattern recognition algorithms to identify and quantify the components in the analyte. The neural signal processing allows for innovative sampling and analysis strategies to be employed with the microsensor. In most situations, the whole response signature from the voltammogram can be used to identify, classify, and quantify an analyte, without dissecting it into component parts. This allows an instrument to be calibrated once for a specific gas or mixture of gases by simple exposure to a multi-component standard rather than by a series of individual gases. The sampled unknown analytes can vary in composition or in concentration; the calibration, sensing, and processing methods of these active voltammetric microsensors can detect, recognize, and

Hierarchy of controls applied to dangerous substances

NARCIS (Netherlands)

Terwoert, J.

2014-01-01

Too often, measures to control workers’ exposure to dangerous substances are taken on an ‘ad-hoc’ basis. Existing processes, procedures and routines are taken for granted, and ‘end-of-pipe’ solutions are installed. In many cases, one relies on the use of personal protective equipment. This may lead

Securing the dangerous UN convoys in Mali

DEFF Research Database (Denmark)

Haugegaard, Rikke; Albrecht, Peter; Ravnkilde, Signe Cold

2017-01-01

It has proven particularly challenging for the UN stabilization mission in Mali (MINUSMA) to transport fuel, food and water to military camps in Sector North on the frontline of the mission. Convoy escorts drain the UN mission of resources and is one of its most dangerous tasks, mainly carried ou...

Polysaccharides purified from wild Cordyceps activate FGF2/FGFR1c signaling

Science.gov (United States)

Zeng, Yangyang; Han, Zhangrun; Yu, Guangli; Hao, Jiejie; Zhang, Lijuan

2015-02-01

Land animals as well as all organisms in ocean synthesize sulfated polysaccharides. Fungi split from animals about 1.5 billion years ago. As fungi make the evolutionary journey from ocean to land, the biggest changes in their living environment may be a sharp decrease in salt concentration. It is established that sulfated polysaccharides interact with hundreds of signaling molecules and facilitate many signaling transduction pathways, including fibroblast growth factor (FGF) and FGF receptor signaling pathway. The disappearance of sulfated polysaccharides in fungi and plants on land might indicate that polysaccharides without sulfation might be sufficient in facilitating protein ligand/receptor interactions in low salinity land. Recently, it was reported that plants on land start to synthesize sulfated polysaccharides in high salt environment, suggesting that fungi might be able to do the same when exposed in such environment. Interestingly, Cordyceps, a fungus habituating inside caterpillar body, is the most valued traditional Chinese Medicine. One of the important pharmaceutical active ingredients in Cordyceps is polysaccharides. Therefore, we hypothesize that the salty environment inside caterpillar body might allow the fungi to synthesize sulfated polysaccharides. To test the hypothesis, we isolated polysaccharides from both lava and sporophore of wild Cordyceps and also from Cordyceps militaris cultured without or with added salts. We then measured the polysaccharide activity using a FGF2/FGFR1c signaling-dependent BaF3 cell proliferation assay and found that polysaccharides isolated from wild Cordyceps activated FGF2/FGFR signaling, indicating that the polysaccharides synthesized by wild Cordyceps are indeed different from those by the cultured mycelium.

Constitutively active signaling by the G protein βγ-subunit mediates intrinsically increased phosphodiesterase-4 activity in human asthmatic airway smooth muscle cells.

Directory of Open Access Journals (Sweden)

Aihua Hu

Full Text Available Signaling by the Gβγ subunit of Gi protein, leading to downstream c-Src-induced activation of the Ras/c-Raf1/MEK-ERK1/2 signaling pathway and its upregulation of phosphodiesterase-4 (PDE4 activity, was recently shown to mediate the heightened contractility in proasthmatic sensitized isolated airway smooth muscle (ASM, as well as allergen-induced airway hyperresponsiveness and inflammation in an in vivo animal model of allergic asthma. This study investigated whether cultured human ASM (HASM cells derived from asthmatic donor lungs exhibit constitutively increased PDE activity that is attributed to intrinsically upregulated Gβγ signaling coupled to c-Src activation of the Ras/MEK/ERK1/2 cascade. We show that, relative to normal cells, asthmatic HASM cells constitutively exhibit markedly increased intrinsic PDE4 activity coupled to heightened Gβγ-regulated phosphorylation of c-Src and ERK1/2, and direct co-localization of the latter with the PDE4D isoform. These signaling events and their induction of heightened PDE activity are acutely suppressed by treating asthmatic HASM cells with a Gβγ inhibitor. Importantly, along with increased Gβγ activation, asthmatic HASM cells also exhibit constitutively increased direct binding of the small Rap1 GTPase-activating protein, Rap1GAP, to the α-subunit of Gi protein, which serves to cooperatively facilitate Ras activation and, thereby, enable enhanced Gβγ-regulated ERK1/2-stimulated PDE activity. Collectively, these data are the first to identify that intrinsically increased signaling via the Gβγ subunit, facilitated by Rap1GAP recruitment to the α-subunit, mediates the constitutively increased PDE4 activity detected in asthmatic HASM cells. These new findings support the notion that interventions targeted at suppressing Gβγ signaling may lead to novel approaches to treat asthma.

Adolescent dispositions for antisocial behavior in context: the roles of neighborhood dangerousness and parental knowledge.

Science.gov (United States)

Trentacosta, Christopher J; Hyde, Luke W; Shaw, Daniel S; Cheong, JeeWon

2009-08-01

This study examined an ecological perspective on the development of antisocial behavior during adolescence, examining direct, additive, and interactive effects of child and both parenting and community factors in relation to youth problem behavior. To address this goal, the authors examined early adolescent dispositional qualities as predictors of boys' antisocial behavior within the context of parents' knowledge of adolescent activities and neighborhood dangerousness. Antisocial behavior was examined using a multimethod latent construct that included self-reported delinquency, symptoms of conduct disorder, and court petitions in a sample of 289 boys from lower socioeconomic status backgrounds who were followed longitudinally from early childhood through adolescence. Results demonstrated direct and additive findings for child prosociality, daring, and negative emotionality, which were qualified by interactions between daring and neighborhood dangerousness, and between prosociality and parental knowledge. The findings have implications for preventive intervention approaches that address the interplay of dispositional and contextual factors to prevent delinquent behavior in adolescence.

Danger defence and risk provision in nuclear law

International Nuclear Information System (INIS)

Breuer, R.

1978-01-01

Starting from the atomic-law term of danger, which is defined as a product of likeliness and volume of damage, the author comments upon the decisive and, as to date, unsolved question of which degree of likeliness a possible course of events must have in order to be taken into consideration as a danger that must be averted. In doing this, it is stressed that the most important point is to find a rationally practicable standard of likeliness or unlikeliness. This standard is then developed from the deterministical point of view. It corresponds with the postulate that effective precautions must be taken against all known causes for incidents and accidents. A standard of practical ratio results from this: damage does not have to be taken into consideration any longer if, due to the precautions taken and the knowledge level of the leading scientists and technicians, if it is not likely to occur. In addition to this preventive protection from danger, paragraph 7, Sec.2 No.3 Atomic Energy Act stipulates another risk under the reservation of precaution, however the technical possibility of realization and the relativity of expenditure and benefit. With regard to these criteria, the author gives his opinion on the judgements of the administrative courts in Wuerzburg and Freiburg which, starting from the same principles, have different points of view on the question of the so-called rupture safety in nuclear power plants. (UN) [de

Kidney sales and the analogy with dangerous employment.

Science.gov (United States)

Malmqvist, Erik

2015-06-01

Proponents of permitting living kidney sales often argue as follows. Many jobs involve significant risks; people are and should be free to take these risks in exchange for money; the risks involved in giving up a kidney are no greater than the risks involved in acceptable hazardous jobs; so people should be free to give up a kidney for money, too. This paper examines this frequently invoked but rarely analysed analogy. Two objections are raised. First, it is far from clear that kidney sales and dangerous jobs involve comparable risks on an appropriately broad comparison. Second, and more importantly, even if they do involve comparable risks it does not follow that kidney sales must be permitted because dangerous jobs are. The analogy assumes that kidney sales are banned for paternalistic reasons. But there may be other, non-paternalistic reasons for the ban. And paternalists, too, can consistently defend the ban even if kidney sales are no riskier than occupations that they find acceptable. Soft paternalists may want to protect would-be vendors from harms that they have not voluntarily chosen. Egalitarian hard paternalists may want to protect already badly off vendors from further worsening their situation. For neither species of paternalist is the size of the risk prevented decisive. I conclude that the analogy with dangerous jobs, while rhetorically powerful, pulls little real argumentative weight. Future debates on living kidney sales should therefore proceed without it.

Intercellular signaling pathways active during and after growth and differentiation of the lumbar vertebral growth plate.

Science.gov (United States)

Dahia, Chitra Lekha; Mahoney, Eric J; Durrani, Atiq A; Wylie, Christopher

2011-06-15

Vertebral growth plates at different postnatal ages were assessed for active intercellular signaling pathways. To generate a spatial and temporal map of the major signaling pathways active in the postnatal mouse lumbar vertebral growth plate. The growth of all long bones is known to occur by cartilaginous growth plates. The growth plate is composed of layers of chondrocyets that actively proliferate, differentiate, die and, are replaced by bone. The role of major cell signaling pathways has been suggested for regulation of the fetal long bones. But not much is known about the molecular or cellular signals that control the postnatal vertebral growth plate and hence postnatal vertebral bone growth. Understanding such molecular mechanisms will help design therapeutic treatments for vertebral growth disorders such as scoliosis. Antibodies against activated downstream intermediates were used to identify cells in the growth plate responding to BMP, TGFβ, and FGF in cryosections of lumbar vertebrae from different postnatal age mice to identify the zones that were responding to these signals. Reporter mice were used to identify the chondrocytes responding to hedgehog (Ihh), and Wnt signaling. We present a spatial/temporal map of these signaling pathways during growth, and differentiation of the mouse lumbar vertebral growth plate. During growth and differentiation of the vertebral growth plate, its different components respond at different times to different intercellular signaling ligands. Response to most of these signals is dramatically downregulated at the end of vertebral growth.

The erroneous signals of detection theory.

Science.gov (United States)

Trimmer, Pete C; Ehlman, Sean M; McNamara, John M; Sih, Andrew

2017-10-25

Signal detection theory has influenced the behavioural sciences for over 50 years. The theory provides a simple equation that indicates numerous 'intuitive' results; e.g. prey should be more prone to take evasive action (in response to an ambiguous cue) if predators are more common. Here, we use analytical and computational models to show that, in numerous biological scenarios, the standard results of signal detection theory do not apply; more predators can result in prey being less responsive to such cues. The standard results need not apply when the probability of danger pertains not just to the present, but also to future decisions. We identify how responses to risk should depend on background mortality and autocorrelation, and that predictions in relation to animal welfare can also be reversed from the standard theory. © 2017 The Author(s).

male knowledge of danger signs of obstetric complications

African Journals Online (AJOL)

Maternal mortality in sub-Saharan Africa has been unacceptably high over the ... In addition to this, the autonomy of pregnant women to access health care is ... practices concerning antenatal care, knowledge of danger signs in pregnancy and ...

Who is a dangerous driver? Socio-demographic and personal determinants of risky traffic behavior

OpenAIRE

Aleksandra Peplińska; Magdalena Wyszomirska-Góra; Piotr Połomski; Marcin Szulc

2015-01-01

Background The aim of this study was to search for comprehensive socio-demographic and personal (personality and temperamental) determinants of risky on-the-road behavior. Based on the results of previous studies, we assumed that the main predictors of dangerous traffic behavior include: internal locus of control, sensation seeking, risk seeking and risk acceptance, as well as high self-esteem, a low level of reactivity combined with a high level of endurance and activity (which together...

Luminance and chromatic signals interact differently with melanopsin activation to control the pupil light response.

Science.gov (United States)

Barrionuevo, Pablo A; Cao, Dingcai

2016-09-01

Intrinsically photosensitive retinal ganglion cells (ipRGCs) express the photopigment melanopsin. These cells receive afferent inputs from rods and cones, which provide inputs to the postreceptoral visual pathways. It is unknown, however, how melanopsin activation is integrated with postreceptoral signals to control the pupillary light reflex. This study reports human flicker pupillary responses measured using stimuli generated with a five-primary photostimulator that selectively modulated melanopsin, rod, S-, M-, and L-cone excitations in isolation, or in combination to produce postreceptoral signals. We first analyzed the light adaptation behavior of melanopsin activation and rod and cones signals. Second, we determined how melanopsin is integrated with postreceptoral signals by testing with cone luminance, chromatic blue-yellow, and chromatic red-green stimuli that were processed by magnocellular (MC), koniocellular (KC), and parvocellular (PC) pathways, respectively. A combined rod and melanopsin response was also measured. The relative phase of the postreceptoral signals was varied with respect to the melanopsin phase. The results showed that light adaptation behavior for all conditions was weaker than typical Weber adaptation. Melanopsin activation combined linearly with luminance, S-cone, and rod inputs, suggesting the locus of integration with MC and KC signals was retinal. The melanopsin contribution to phasic pupil responses was lower than luminance contributions, but much higher than S-cone contributions. Chromatic red-green modulation interacted with melanopsin activation nonlinearly as described by a "winner-takes-all" process, suggesting the integration with PC signals might be mediated by a postretinal site.

Activated AKT/PKB signaling in C. elegans uncouples temporally distinct outputs of DAF-2/insulin-like signaling

Directory of Open Access Journals (Sweden)

Hanselman Keaton B

2006-10-01

Full Text Available Abstract Background In the nematode, Caenorhabditis elegans, a conserved insulin-like signaling pathway controls larval development, stress resistance and adult lifespan. AGE-1, a homolog of the p110 catalytic subunit of phosphoinositide 3-kinases (PI3K comprises the major known effector pathway downstream of the insulin receptor, DAF-2. Phospholipid products of AGE-1/PI3K activate AKT/PKB kinase signaling via PDK-1. AKT/PKB signaling antagonizes nuclear translocation of the DAF-16/FOXO transcription factor. Reduced AGE-1/PI3K signaling permits DAF-16 to direct dauer larval arrest and promote long lifespan in adult animals. In order to study the downstream effectors of AGE-1/PI3K signaling in C. elegans, we conducted a genetic screen for mutations that suppress the constitutive dauer arrest phenotype of age-1(mg109 animals. Results This report describes mutations recovered in a screen for suppressors of the constitutive dauer arrest (daf-C phenotype of age-1(mg109. Two mutations corresponded to alleles of daf-16. Two mutations were gain-of-function alleles in the genes, akt-1 and pdk-1, encoding phosphoinositide-dependent serine/threonine kinases. A fifth mutation, mg227, located on chromosome X, did not correspond to any known dauer genes, suggesting that mg227 may represent a new component of the insulin pathway. Genetic epistasis analysis by RNAi showed that reproductive development in age-1(mg109;akt-1(mg247 animals was dependent on the presence of pdk-1. Similarly, reproductive development in age-1(mg109;pdk-1(mg261 animals was dependent on akt-1. However, reproductive development in age-1(mg109; mg227 animals required only akt-1, and pdk-1 activity was dispensable in this background. Interestingly, while mg227 suppressed dauer arrest in age-1(mg109 animals, it enhanced the long lifespan phenotype. In contrast, akt-1(mg247 and pdk-1(mg261 did not affect lifespan or stress resistance, while both daf-16 alleles fully suppressed these

Activated AKT/PKB signaling in C. elegans uncouples temporally distinct outputs of DAF-2/insulin-like signaling.

Science.gov (United States)

Gami, Minaxi S; Iser, Wendy B; Hanselman, Keaton B; Wolkow, Catherine A

2006-10-04

In the nematode, Caenorhabditis elegans, a conserved insulin-like signaling pathway controls larval development, stress resistance and adult lifespan. AGE-1, a homolog of the p110 catalytic subunit of phosphoinositide 3-kinases (PI3K) comprises the major known effector pathway downstream of the insulin receptor, DAF-2. Phospholipid products of AGE-1/PI3K activate AKT/PKB kinase signaling via PDK-1. AKT/PKB signaling antagonizes nuclear translocation of the DAF-16/FOXO transcription factor. Reduced AGE-1/PI3K signaling permits DAF-16 to direct dauer larval arrest and promote long lifespan in adult animals. In order to study the downstream effectors of AGE-1/PI3K signaling in C. elegans, we conducted a genetic screen for mutations that suppress the constitutive dauer arrest phenotype of age-1(mg109) animals. This report describes mutations recovered in a screen for suppressors of the constitutive dauer arrest (daf-C) phenotype of age-1(mg109). Two mutations corresponded to alleles of daf-16. Two mutations were gain-of-function alleles in the genes, akt-1 and pdk-1, encoding phosphoinositide-dependent serine/threonine kinases. A fifth mutation, mg227, located on chromosome X, did not correspond to any known dauer genes, suggesting that mg227 may represent a new component of the insulin pathway. Genetic epistasis analysis by RNAi showed that reproductive development in age-1(mg109);akt-1(mg247) animals was dependent on the presence of pdk-1. Similarly, reproductive development in age-1(mg109);pdk-1(mg261) animals was dependent on akt-1. However, reproductive development in age-1(mg109); mg227 animals required only akt-1, and pdk-1 activity was dispensable in this background. Interestingly, while mg227 suppressed dauer arrest in age-1(mg109) animals, it enhanced the long lifespan phenotype. In contrast, akt-1(mg247) and pdk-1(mg261) did not affect lifespan or stress resistance, while both daf-16 alleles fully suppressed these phenotypes. A screen for suppressors of PI3K

TLR4 Signaling Pathway Modulators as Potential Therapeutics in Inflammation and Sepsis

Directory of Open Access Journals (Sweden)

Nikolay N. Kuzmich

2017-10-01

Full Text Available Toll-Like Receptor 4 (TLR4 signal pathway plays an important role in initiating the innate immune response and its activation by bacterial endotoxin is responsible for chronic and acute inflammatory disorders that are becoming more and more frequent in developed countries. Modulation of the TLR4 pathway is a potential strategy to specifically target these pathologies. Among the diseases caused by TLR4 abnormal activation by bacterial endotoxin, sepsis is the most dangerous one because it is a life-threatening acute system inflammatory condition that still lacks specific pharmacological treatment. Here, we review molecules at a preclinical or clinical phase of development, that are active in inhibiting the TLR4-MyD88 and TLR4-TRIF pathways in animal models. These are low-molecular weight compounds of natural and synthetic origin that can be considered leads for drug development. The results of in vivo studies in the sepsis model and the mechanisms of action of drug leads are presented and critically discussed, evidencing the differences in treatment results from rodents to humans.

Dangers and Pleasures

DEFF Research Database (Denmark)

Järvinen, Margaretha Maria; Østergaard, Jeanette

2011-01-01

to ‘hard’ illegal drugs; and, finally, the pro-drug position, characteristic of drug users with low risk perceptions and high pleasure-orientation. We use the focus group interviews to demonstrate how youths occupying these differing positions argue for and against drugs and which risks and pleasures......This is a study of young people’s conceptions of illegal drug use as dangerous and/or pleasurable and an analysis of the relationship between attitudes to drugs, drinking, friends’ reported drug use and own experience with drug use and drinking. The article applies a mixed methods approach using...... both survey data and focus group interviews. The main statistical method is Multiple Correspondence Analysis (MCA), which constructs a social space of young people’s attitudes to drugs and drug experiences relationally. We identify four interrelated positions on illegal drug use among 17 to 19-year...

Insulin signaling regulates fatty acid catabolism at the level of CoA activation.

Directory of Open Access Journals (Sweden)

Xiaojun Xu

2012-01-01

Full Text Available The insulin/IGF signaling pathway is a highly conserved regulator of metabolism in flies and mammals, regulating multiple physiological functions including lipid metabolism. Although insulin signaling is known to regulate the activity of a number of enzymes in metabolic pathways, a comprehensive understanding of how the insulin signaling pathway regulates metabolic pathways is still lacking. Accepted knowledge suggests the key regulated step in triglyceride (TAG catabolism is the release of fatty acids from TAG via the action of lipases. We show here that an additional, important regulated step is the activation of fatty acids for beta-oxidation via Acyl Co-A synthetases (ACS. We identify pudgy as an ACS that is transcriptionally regulated by direct FOXO action in Drosophila. Increasing or reducing pudgy expression in vivo causes a decrease or increase in organismal TAG levels respectively, indicating that pudgy expression levels are important for proper lipid homeostasis. We show that multiple ACSs are also transcriptionally regulated by insulin signaling in mammalian cells. In sum, we identify fatty acid activation onto CoA as an important, regulated step in triglyceride catabolism, and we identify a mechanistic link through which insulin regulates lipid homeostasis.

75 FR 63534 - International Standards on the Transport of Dangerous Goods; Public Meeting

Science.gov (United States)

2010-10-15

...: Any person wishing to participate in the public meeting should send an e-mail to [email protected] Standards on the Transport of Dangerous Goods; Public Meeting AGENCY: Pipeline and Hazardous Materials... the 38th session of the United Nations Sub-Committee of Experts on the Transport of Dangerous Goods...

Human immunodeficiency virus long terminal repeat responds to T-cell activation signals

International Nuclear Information System (INIS)

Tong-Starksen, S.E.; Luciw, P.A.; Peterlin, B.M.

1987-01-01

Human immunodeficiency virus (HIV), the causative agent of AIDS, infects and kills lymphoid cells bearing the CD4 antigen. In an infected cell, a number of cellular as well as HIV-encoded gene products determine the levels of viral gene expression and HIV replication. Efficient HIV replication occurs in activated T cells. Utilizing transient expression assays, the authors show that gene expression directed by the HIV long terminal repeat (LTR) increases in response to T-cell activation signals. The effects of T-cell activation and of the HIV-encoded trans-activator (TAT) are multiplicative. Analysis of mutations and deletions in the HIV LTR reveals that the region responding to T-cell activation signals is located at positions -105 to -80. These sequences are composed of two direct repeats, which are homologous to the core transcriptional enhancer elements in the simian virus 40 genome. The studies reveal that these elements function as the HIV enhancer. By acting directly on the HIV LTR, T-cell activation may play an important role in HIV gene expression and in the activation of latent HIV

Dendritic calcium channels and their activation by synaptic signals in auditory coincidence detector neurons.

Science.gov (United States)

Blackmer, Trillium; Kuo, Sidney P; Bender, Kevin J; Apostolides, Pierre F; Trussell, Laurence O

2009-08-01

The avian nucleus laminaris (NL) encodes the azimuthal location of low-frequency sound sources by detecting the coincidence of binaural signals. Accurate coincidence detection requires precise developmental regulation of the lengths of the fine, bitufted dendrites that characterize neurons in NL. Such regulation has been suggested to be driven by local, synaptically mediated, dendritic signals such as Ca(2+). We examined Ca(2+) signaling through patch clamp and ion imaging experiments in slices containing nucleus laminaris from embryonic chicks. Voltage-clamp recordings of neurons located in the NL showed the presence of large Ca(2+) currents of two types, a low voltage-activated, fast inactivating Ni(2+) sensitive channel resembling mammalian T-type channels, and a high voltage-activated, slowly inactivating Cd(2+) sensitive channel. Two-photon Ca(2+) imaging showed that both channel types were concentrated on dendrites, even at their distal tips. Single action potentials triggered synaptically or by somatic current injection immediately elevated Ca(2+) throughout the entire cell. Ca(2+) signals triggered by subthreshold synaptic activity were highly localized. Thus when electrical activity is suprathreshold, Ca(2+) channels ensure that Ca(2+) rises in all dendrites, even those that are synaptically inactive.

Nanobody-Based Biologics for Modulating Purinergic Signaling in Inflammation and Immunity

Directory of Open Access Journals (Sweden)

Stephan Menzel

2018-03-01

Full Text Available Adenosine triphosphate (ATP and nicotinamide adenine dinucleotide (NAD+ are released as danger signals from cells during infection and sterile inflammation. In the extracellular compartment ATP is converted by CD39, CD73, and other ecto-enzymes into metabolites that modulate the activity of T cells and macrophages. While ATP mediates pro-inflammatory signals via P2X7 and other P2 receptors, adenosine triggers anti-inflammatory signaling via the adenosine 2a receptor (Adora2a and other P1 receptors. The latter also plays a role in maintaining an immunosuppressive tumor microenvironment. NAD+ is converted by CD38, CD203 and other ecto-enzymes to the Ca2+ mobilizing messengers cyclic ADP-ribose and ADP-ribose, and to adenosine. Recent findings on the roles of CD38, CD39, CD73, CD203, P2X7, and Adora2a in inflammation and immunity underscore the potential of these proteins as drug targets. However, available small molecule inhibitors often lack specificity and mediate unwanted off-target toxicity. Nanobodies – single domain antibodies derived from heavy chain antibodies that naturally occur in camelids – display a propensity to bind functional epitopes not accessible to conventional antibodies. Like conventional antibodies, nanobodies and nanobody-based biologics are highly specific and have well-understood, tunable in vivo pharmacodynamics with little if any toxicity. Nanobodies thus represent attractive alternatives to small molecule inhibitors for modulating purinergic signaling in inflammation and immunity. Here we review recent progress made in developing nanobodies against key targets of purinergic signaling.

Nanobody-Based Biologics for Modulating Purinergic Signaling in Inflammation and Immunity.

Science.gov (United States)

Menzel, Stephan; Schwarz, Nicole; Haag, Friedrich; Koch-Nolte, Friedrich

2018-01-01

Adenosine triphosphate (ATP) and nicotinamide adenine dinucleotide (NAD + ) are released as danger signals from cells during infection and sterile inflammation. In the extracellular compartment ATP is converted by CD39, CD73, and other ecto-enzymes into metabolites that modulate the activity of T cells and macrophages. While ATP mediates pro-inflammatory signals via P2X7 and other P2 receptors, adenosine triggers anti-inflammatory signaling via the adenosine 2a receptor (Adora2a) and other P1 receptors. The latter also plays a role in maintaining an immunosuppressive tumor microenvironment. NAD + is converted by CD38, CD203 and other ecto-enzymes to the Ca 2+ mobilizing messengers cyclic ADP-ribose and ADP-ribose, and to adenosine. Recent findings on the roles of CD38, CD39, CD73, CD203, P2X7, and Adora2a in inflammation and immunity underscore the potential of these proteins as drug targets. However, available small molecule inhibitors often lack specificity and mediate unwanted off-target toxicity. Nanobodies - single domain antibodies derived from heavy chain antibodies that naturally occur in camelids - display a propensity to bind functional epitopes not accessible to conventional antibodies. Like conventional antibodies, nanobodies and nanobody-based biologics are highly specific and have well-understood, tunable in vivo pharmacodynamics with little if any toxicity. Nanobodies thus represent attractive alternatives to small molecule inhibitors for modulating purinergic signaling in inflammation and immunity. Here we review recent progress made in developing nanobodies against key targets of purinergic signaling.

An alternative mode of CD43 signal transduction activates pro-survival pathways of T lymphocytes.

Science.gov (United States)

Bravo-Adame, Maria Elena; Vera-Estrella, Rosario; Barkla, Bronwyn J; Martínez-Campos, Cecilia; Flores-Alcantar, Angel; Ocelotl-Oviedo, Jose Pablo; Pedraza-Alva, Gustavo; Rosenstein, Yvonne

2017-01-01

CD43 is one of the most abundant co-stimulatory molecules on a T-cell surface; it transduces activation signals through its cytoplasmic domain, contributing to modulation of the outcome of T-cell responses. The aim of this study was to uncover new signalling pathways regulated by this sialomucin. Analysis of changes in protein abundance allowed us to identify pyruvate kinase isozyme M2 (PKM2), an enzyme of the glycolytic pathway, as an element potentially participating in the signalling cascade resulting from the engagement of CD43 and the T-cell receptor (TCR). We found that the glycolytic activity of this enzyme was not significantly increased in response to TCR+CD43 co-stimulation, but that PKM2 was tyrosine phosphorylated, suggesting that it was performing moonlight functions. We report that phosphorylation of both Y 105 of PKM2 and of Y 705 of signal transducer and activator of transcription 3 was induced in response to TCR+CD43 co-stimulation, resulting in activation of the mitogen-activated protein kinase kinase 5/extracellular signal-regulated kinase 5 (MEK5/ERK5) pathway. ERK5 and the cAMP response element binding protein (CREB) were activated, and c-Myc and nuclear factor-κB (p65) nuclear localization, as well as Bad phosphorylation, were augmented. Consistent with this, expression of human CD43 in a murine T-cell hybridoma favoured cell survival. Altogether, our data highlight novel signalling pathways for the CD43 molecule in T lymphocytes, and underscore a role for CD43 in promoting cell survival through non-glycolytic functions of metabolic enzymes. © 2016 John Wiley & Sons Ltd.

Herpes simplex virus triggers activation of calcium-signaling pathways

Science.gov (United States)

Cheshenko, Natalia; Del Rosario, Brian; Woda, Craig; Marcellino, Daniel; Satlin, Lisa M.; Herold, Betsy C.

2003-01-01

The cellular pathways required for herpes simplex virus (HSV) invasion have not been defined. To test the hypothesis that HSV entry triggers activation of Ca2+-signaling pathways, the effects on intracellular calcium concentration ([Ca2+]i) after exposure of cells to HSV were examined. Exposure to virus results in a rapid and transient increase in [Ca2+]i. Pretreatment of cells with pharmacological agents that block release of inositol 1,4,5-triphosphate (IP3)–sensitive endoplasmic reticulum stores abrogates the response. Moreover, treatment of cells with these pharmacological agents inhibits HSV infection and prevents focal adhesion kinase (FAK) phosphorylation, which occurs within 5 min after viral infection. Viruses deleted in glycoprotein L or glycoprotein D, which bind but do not penetrate, fail to induce a [Ca2+]i response or trigger FAK phosphorylation. Together, these results support a model for HSV infection that requires activation of IP3-responsive Ca2+-signaling pathways and that is associated with FAK phosphorylation. Defining the pathway of viral invasion may lead to new targets for anti-viral therapy. PMID:14568989

Safety assessment of dangerous goods transport enterprise based on the relative entropy aggregation in group decision making model.

Science.gov (United States)

Wu, Jun; Li, Chengbing; Huo, Yueying

2014-01-01

Safety of dangerous goods transport is directly related to the operation safety of dangerous goods transport enterprise. Aiming at the problem of the high accident rate and large harm in dangerous goods logistics transportation, this paper took the group decision making problem based on integration and coordination thought into a multiagent multiobjective group decision making problem; a secondary decision model was established and applied to the safety assessment of dangerous goods transport enterprise. First of all, we used dynamic multivalue background and entropy theory building the first level multiobjective decision model. Secondly, experts were to empower according to the principle of clustering analysis, and combining with the relative entropy theory to establish a secondary rally optimization model based on relative entropy in group decision making, and discuss the solution of the model. Then, after investigation and analysis, we establish the dangerous goods transport enterprise safety evaluation index system. Finally, case analysis to five dangerous goods transport enterprises in the Inner Mongolia Autonomous Region validates the feasibility and effectiveness of this model for dangerous goods transport enterprise recognition, which provides vital decision making basis for recognizing the dangerous goods transport enterprises.

PAK1 is a breast cancer oncogene that coordinately activates MAPK and MET signaling.

Science.gov (United States)

Shrestha, Y; Schafer, E J; Boehm, J S; Thomas, S R; He, F; Du, J; Wang, S; Barretina, J; Weir, B A; Zhao, J J; Polyak, K; Golub, T R; Beroukhim, R; Hahn, W C

2012-07-19

Activating mutations in the RAS family or BRAF frequently occur in many types of human cancers but are rarely detected in breast tumors. However, activation of the RAS-RAF-MEK-ERK MAPK pathway is commonly observed in human breast cancers, suggesting that other genetic alterations lead to activation of this signaling pathway. To identify breast cancer oncogenes that activate the MAPK pathway, we screened a library of human kinases for their ability to induce anchorage-independent growth in a derivative of immortalized human mammary epithelial cells (HMLE). We identified p21-activated kinase 1 (PAK1) as a kinase that permitted HMLE cells to form anchorage-independent colonies. PAK1 is amplified in several human cancer types, including 30--33% of breast tumor samples and cancer cell lines. The kinase activity of PAK1 is necessary for PAK1-induced transformation. Moreover, we show that PAK1 simultaneously activates MAPK and MET signaling; the latter via inhibition of merlin. Disruption of these activities inhibits PAK1-driven anchorage-independent growth. These observations establish PAK1 amplification as an alternative mechanism for MAPK activation in human breast cancer and credential PAK1 as a breast cancer oncogene that coordinately regulates multiple signaling pathways, the cooperation of which leads to malignant transformation.

Fgf signaling controls pharyngeal taste bud formation through miR-200 and Delta-Notch activity.

Science.gov (United States)

Kapsimali, Marika; Kaushik, Anna-Lila; Gibon, Guillaume; Dirian, Lara; Ernest, Sylvain; Rosa, Frederic M

2011-08-01

Taste buds, the taste sensory organs, are conserved in vertebrates and composed of distinct cell types, including taste receptor, basal/presynaptic and support cells. Here, we characterize zebrafish taste bud development and show that compromised Fgf signaling in the larva results in taste bud reduction and disorganization. We determine that Fgf activity is required within pharyngeal endoderm for formation of Calb2b(+) cells and reveal miR-200 and Delta-Notch signaling as key factors in this process. miR-200 knock down shows that miR-200 activity is required for taste bud formation and in particular for Calb2b(+) cell formation. Compromised delta activity in mib(-/-) dramatically reduces the number of Calb2b(+) cells and increases the number of 5HT(+) cells. Conversely, larvae with increased Notch activity and ascl1a(-/-) mutants are devoid of 5HT(+) cells, but have maintained and increased Calb2b(+) cells, respectively. These results show that Delta-Notch signaling is required for intact taste bud organ formation. Consistent with this, Notch activity restores Calb2b(+) cell formation in pharyngeal endoderm with compromised Fgf signaling, but fails to restore the formation of these cells after miR-200 knock down. Altogether, this study provides genetic evidence that supports a novel model where Fgf regulates Delta-Notch signaling, and subsequently miR-200 activity, in order to promote taste bud cell type differentiation.

M2 macrophages activate WNT signaling pathway in epithelial cells: relevance in ulcerative colitis.

Directory of Open Access Journals (Sweden)

Jesús Cosín-Roger

Full Text Available Macrophages, which exhibit great plasticity, are important components of the inflamed tissue and constitute an essential element of regenerative responses. Epithelial Wnt signalling is involved in mechanisms of proliferation and differentiation and expression of Wnt ligands by macrophages has been reported. We aim to determine whether the macrophage phenotype determines the expression of Wnt ligands, the influence of the macrophage phenotype in epithelial activation of Wnt signalling and the relevance of this pathway in ulcerative colitis. Human monocyte-derived macrophages and U937-derived macrophages were polarized towards M1 or M2 phenotypes and the expression of Wnt1 and Wnt3a was analyzed by qPCR. The effects of macrophages and the role of Wnt1 were analyzed on the expression of β-catenin, Tcf-4, c-Myc and markers of cell differentiation in a co-culture system with Caco-2 cells. Immunohistochemical staining of CD68, CD206, CD86, Wnt1, β-catenin and c-Myc were evaluated in the damaged and non-damaged mucosa of patients with UC. We also determined the mRNA expression of Lgr5 and c-Myc by qPCR and protein levels of β-catenin by western blot. Results show that M2, and no M1, activated the Wnt signaling pathway in co-culture epithelial cells through Wnt1 which impaired enterocyte differentiation. A significant increase in the number of CD206+ macrophages was observed in the damaged mucosa of chronic vs newly diagnosed patients. CD206 immunostaining co-localized with Wnt1 in the mucosa and these cells were associated with activation of canonical Wnt signalling pathway in epithelial cells and diminution of alkaline phosphatase activity. Our results show that M2 macrophages, and not M1, activate Wnt signalling pathways and decrease enterocyte differentiation in co-cultured epithelial cells. In the mucosa of UC patients, M2 macrophages increase with chronicity and are associated with activation of epithelial Wnt signalling and diminution in

FHL1 activates myostatin signalling in skeletal muscle and promotes atrophy

OpenAIRE

Kemp, P; Lee, JY; lori, O; Wells, D

2015-01-01

Myostatin is a TGFβ family ligand that reduces muscle mass. In cancer cells, TGFβ signalling is increased by the protein FHL1. Consequently, FHL1 may promote signalling by myostatin. We therefore tested the ability of FHL1 to regulate myostatin function. FHL1 increased the myostatin activity on a SMAD reporter and increased myostatin dependent myotube wasting. In mice, independent expression of myostatin reduced fibre diameter whereas FHL1 increased fibre diameter, both consistent with previo...

Task control signals in pediatric Tourette syndrome show evidence of immature and anomalous functional activity

Directory of Open Access Journals (Sweden)

Jessica A Church

2009-11-01

Full Text Available Tourette Syndrome (TS is a pediatric movement disorder that may affect control signaling in the brain. Previous work has proposed a dual-networks architecture of control processing involving a task-maintenance network and an adaptive control network (Dosenbach et al., 2008. A prior resting-state functional connectivity MRI (rs-fcMRI analysis in TS has revealed functional immaturity in both putative control networks, with “anomalous” correlations (i.e. correlations outside the typical developmental range limited to the adaptive control network (Church et al., 2009. The present study used functional MRI (fMRI to study brain activity related to adaptive control (by studying start-cues signals, and to task-maintenance (by studying signals sustained across a task set. Two hypotheses from the previous rs-fcMRI results were tested. First, adaptive control (i.e., start-cue activity will be altered in TS, including activity inconsistent with typical development (“anomalous”. Second, group differences found in task maintenance (i.e., sustained activity will be consistent with functional immaturity in TS. We examined regions found through a direct comparison of adolescents with and without TS, as well as regions derived from a previous investigation that showed differences between unaffected children and adults. The TS group showed decreased start-cue signal magnitude in regions where start-cue activity is unchanged over typical development, consistent with anomalous adaptive control. The TS group also had higher magnitude sustained signals in frontal cortex regions that overlapped with regions showing differences over typical development, consistent with immature task maintenance in TS. The results demonstrate task-related fMRI signal differences anticipated by the atypical functional connectivity found previously in adolescents with TS, strengthening the evidence for functional immaturity and anomalous signaling in control networks in adolescents

Drug Modulators of B Cell Signaling Pathways and Epstein-Barr Virus Lytic Activation.

Science.gov (United States)

Kosowicz, John G; Lee, Jaeyeun; Peiffer, Brandon; Guo, Zufeng; Chen, Jianmeng; Liao, Gangling; Hayward, S Diane; Liu, Jun O; Ambinder, Richard F

2017-08-15

Epstein-Barr virus (EBV) is a ubiquitous human gammaherpesvirus that establishes a latency reservoir in B cells. In this work, we show that ibrutinib, idelalisib, and dasatinib, drugs that block B cell receptor (BCR) signaling and are used in the treatment of hematologic malignancies, block BCR-mediated lytic induction at clinically relevant doses. We confirm that the immunosuppressive drugs cyclosporine and tacrolimus also inhibit BCR-mediated lytic induction but find that rapamycin does not inhibit BCR-mediated lytic induction. Further investigation shows that mammalian target of rapamycin complex 2 (mTORC2) contributes to BCR-mediated lytic induction and that FK506-binding protein 12 (FKBP12) binding alone is not adequate to block activation. Finally, we show that BCR signaling can activate EBV lytic induction in freshly isolated B cells from peripheral blood mononuclear cells (PBMCs) and that activation can be inhibited by ibrutinib or idelalisib. IMPORTANCE EBV establishes viral latency in B cells. Activation of the B cell receptor pathway activates lytic viral expression in cell lines. Here we show that drugs that inhibit important kinases in the BCR signaling pathway inhibit activation of lytic viral expression but do not inhibit several other lytic activation pathways. Immunosuppressant drugs such as cyclosporine and tacrolimus but not rapamycin also inhibit BCR-mediated EBV activation. Finally, we show that BCR activation of lytic infection occurs not only in tumor cell lines but also in freshly isolated B cells from patients and that this activation can be blocked by BCR inhibitors. Copyright © 2017 American Society for Microbiology.

Activation of PKA/CREB Signaling is Involved in BMP9-Induced Osteogenic Differentiation of Mesenchymal Stem Cells

Directory of Open Access Journals (Sweden)

Hongyu Zhang

2015-09-01

Full Text Available Background/Aims: BMP9 is highly capable of promoting osteogenic differentiation of mesenchymal stem cells (MSCs although the molecular mechanism involved is largely unknown. Here, we explored the detail role of PKA/CREB signaling in BMP9-induced osteogenic differentiation. Methods: Activation status of PKA/CREB signaling is assessed by nonradioactive assay and Western blot. Using PKA inhibitors and a dominant negative protein of CREB (A-CREB, we investigated the effect of PKA/CREB signaling on BMP9-induced osteogenic differentiation. Results: We found that BMP9 promotes PKA activity and enhances CREB phosphorylation in MSCs. BMP9 is shown to down-regulate protein kinase A inhibitor γ (PKIγ expression. We demonstrated that PKA inhibitors suppress BMP9-induced early osteogenic marker alkaline phosphatase (ALP activity in MSCs as well as late osteogenic markers osteopontin (OPN, osteocalcin (OCN and matrix mineralization. We found that PKA inhibitor reduces BMP9-induced Runx2 activation and p38 phosphorylation in MSCs. Lastly, interference of CREB function by A-CREB decreased BMP9-induced osteogenic differentiation as well. Conclusion: Our results revealed that BMP9 may activate PKA/CREB signaling in MSCs through suppression of PKIγ expression. It is noteworthy that inhibition of PKA/CREB signaling may impair BMP9-induced osteogenic differentiation of MSCs, implying that activation of PKA/CREB signaling is required for BMP9 osteoinductive activity.

Constitutively active Notch1 induces growth arrest of HPV-positive cervical cancer cells via separate signaling pathways

International Nuclear Information System (INIS)

Talora, Claudio; Cialfi, Samantha; Segatto, Oreste; Morrone, Stefania; Kim Choi, John; Frati, Luigi; Paolo Dotto, Gian; Gulino, Alberto; Screpanti, Isabella

2005-01-01

Notch signaling plays a key role in cell-fate determination and differentiation in different organisms and cell types. Several reports suggest that Notch signaling may be involved in neoplastic transformation. However, in primary keratinocytes, Notch1 can function as a tumor suppressor. Similarly, in HPV-positive cervical cancer cells, constitutively active Notch1 signaling was found to cause growth suppression. Activated Notch1 in these cells represses viral E6/E7 expression through AP-1 down-modulation, resulting in increased p53 expression and a block of pRb hyperphosphorylation. Here we show that in cervical cancer cell lines in which Notch1 ability to repress AP-1 activity is impaired, Notch1-enforced expression elicits an alternative pathway leading to growth arrest. Indeed, activated Notch1 signaling suppresses activity of the helix-loop-helix transcription factor E47, via ERK1/2 activation, resulting in inhibition of cell cycle progression. Moreover, we found that RBP-Jκ-dependent Notch signaling is specifically repressed in cervical cancer cells and this repression could provide one such mechanism that needs to be activated for cervical carcinogenesis. Finally, we show that inhibition of endogenous Notch1 signaling, although results in a proliferative advantage, sensitizes cervical cancer cell lines to drug-induced apoptosis. Together, our results provide novel molecular insights into Notch1-dependent growth inhibitory effects, counteracting the transforming potential of HPV

Review: Mitogen-Activated Protein kinases in nutritional signaling in Arabidopsis

KAUST Repository

Chardin, Camille; Schenk, Sebastian T.; Hirt, Heribert; Colcombet, Jean; Krapp, Anne

2017-01-01

Mitogen-Activated Protein Kinase (MAPK) cascades are functional modules widespread among eukaryotic organisms. In plants, these modules are encoded by large multigenic families and are involved in many biological processes ranging from stress responses to cellular differentiation and organ development. Furthermore, MAPK pathways are involved in the perception of environmental and physiological modifications. Interestingly, some MAPKs play a role in several signaling networks and could have an integrative function for the response of plants to their environment. In this review, we describe the classification of MAPKs and highlight some of their biochemical actions. We performed an in silico analysis of MAPK gene expression in response to nutrients supporting their involvement in nutritional signaling. While several MAPKs have been identified as players in sugar, nitrogen, phosphate, iron and potassium-related signaling pathways, their biochemical functions are yet mainly unknown. The integration of these regulatory cascades in the current understanding of nutrient signaling is discussed and potential new avenues for approaches toward plants with higher nutrient use efficiencies are evoked.

Review: Mitogen-Activated Protein kinases in nutritional signaling in Arabidopsis

KAUST Repository

Chardin, Camille

2017-04-14

Mitogen-Activated Protein Kinase (MAPK) cascades are functional modules widespread among eukaryotic organisms. In plants, these modules are encoded by large multigenic families and are involved in many biological processes ranging from stress responses to cellular differentiation and organ development. Furthermore, MAPK pathways are involved in the perception of environmental and physiological modifications. Interestingly, some MAPKs play a role in several signaling networks and could have an integrative function for the response of plants to their environment. In this review, we describe the classification of MAPKs and highlight some of their biochemical actions. We performed an in silico analysis of MAPK gene expression in response to nutrients supporting their involvement in nutritional signaling. While several MAPKs have been identified as players in sugar, nitrogen, phosphate, iron and potassium-related signaling pathways, their biochemical functions are yet mainly unknown. The integration of these regulatory cascades in the current understanding of nutrient signaling is discussed and potential new avenues for approaches toward plants with higher nutrient use efficiencies are evoked.

Loss of Pancreas upon Activated Wnt Signaling Is Concomitant with Emergence of Gastrointestinal Identity

Science.gov (United States)

Herrero-Martin, Griselda; Puri, Sapna; Taketo, Makoto Mark; Rojas, Anabel; Hebrok, Matthias; Cano, David A.

2016-01-01

Organ formation is achieved through the complex interplay between signaling pathways and transcriptional cascades. The canonical Wnt signaling pathway plays multiple roles during embryonic development including patterning, proliferation and differentiation in distinct tissues. Previous studies have established the importance of this pathway at multiple stages of pancreas formation as well as in postnatal organ function and homeostasis. In mice, gain-of-function experiments have demonstrated that activation of the canonical Wnt pathway results in pancreatic hypoplasia, a phenomenon whose underlying mechanisms remains to be elucidated. Here, we show that ectopic activation of epithelial canonical Wnt signaling causes aberrant induction of gastric and intestinal markers both in the pancreatic epithelium and mesenchyme, leading to the development of gut-like features. Furthermore, we provide evidence that β -catenin-induced impairment of pancreas formation depends on Hedgehog signaling. Together, our data emphasize the developmental plasticity of pancreatic progenitors and further underscore the key role of precise regulation of signaling pathways to maintain appropriate organ boundaries. PMID:27736991

Focused sunlight factor of forest fire danger assessment using Web-GIS and RS technologies

Science.gov (United States)

Baranovskiy, Nikolay V.; Sherstnyov, Vladislav S.; Yankovich, Elena P.; Engel, Marina V.; Belov, Vladimir V.

2016-08-01

Timiryazevskiy forestry of Tomsk region (Siberia, Russia) is a study area elaborated in current research. Forest fire danger assessment is based on unique technology using probabilistic criterion, statistical data on forest fires, meteorological conditions, forest sites classification and remote sensing data. MODIS products are used for estimating some meteorological conditions and current forest fire situation. Geonformation technologies are used for geospatial analysis of forest fire danger situation on controlled forested territories. GIS-engine provides opportunities to construct electronic maps with different levels of forest fire probability and support raster layer for satellite remote sensing data on current forest fires. Web-interface is used for data loading on specific web-site and for forest fire danger data representation via World Wide Web. Special web-forms provide interface for choosing of relevant input data in order to process the forest fire danger data and assess the forest fire probability.

MMTV-Wnt1 and -DeltaN89beta-catenin induce canonical signaling in distinct progenitors and differentially activate Hedgehog signaling within mammary tumors.

Directory of Open Access Journals (Sweden)

Brigitte Teissedre

Full Text Available Canonical Wnt/beta-catenin signaling regulates stem/progenitor cells and, when perturbed, induces many human cancers. A significant proportion of human breast cancer is associated with loss of secreted Wnt antagonists and mice expressing MMTV-Wnt1 and MMTV-DeltaN89beta-catenin develop mammary adenocarcinomas. Many studies have assumed these mouse models of breast cancer to be equivalent. Here we show that MMTV-Wnt1 and MMTV-DeltaN89beta-catenin transgenes induce tumors with different phenotypes. Using axin2/conductin reporter genes we show that MMTV-Wnt1 and MMTV-DeltaN89beta-catenin activate canonical Wnt signaling within distinct cell-types. DeltaN89beta-catenin activated signaling within a luminal subpopulation scattered along ducts that exhibited a K18(+ER(-PR(-CD24(highCD49f(low profile and progenitor properties. In contrast, MMTV-Wnt1 induced canonical signaling in K14(+ basal cells with CD24/CD49f profiles characteristic of two distinct stem/progenitor cell-types. MMTV-Wnt1 produced additional profound effects on multiple cell-types that correlated with focal activation of the Hedgehog pathway. We document that large melanocytic nevi are a hitherto unreported hallmark of early hyperplastic Wnt1 glands. These nevi formed along the primary mammary ducts and were associated with Hedgehog pathway activity within a subset of melanocytes and surrounding stroma. Hh pathway activity also occurred within tumor-associated stromal and K14(+/p63(+ subpopulations in a manner correlated with Wnt1 tumor onset. These data show MMTV-Wnt1 and MMTV-DeltaN89beta-catenin induce canonical signaling in distinct progenitors and that Hedgehog pathway activation is linked to melanocytic nevi and mammary tumor onset arising from excess Wnt1 ligand. They further suggest that Hedgehog pathway activation maybe a critical component and useful indicator of breast tumors arising from unopposed Wnt1 ligand.

The principles of measuring forest fire danger

Science.gov (United States)

H. T. Gisborne

1936-01-01

Research in fire danger measurement was commenced in 1922 at the Northern Rocky Mountain Forest and Range Experiment Station of the U. S. Forest Service, with headquarters at Missoula, Mont. Since then investigations have been made concerning ( 1) what to measure, (2) how to measure, and ( 3) field use of these measurements. In all cases the laboratory or restricted...

The potent, indirect adenosine monophosphate-activated protein kinase activator R419 attenuates mitogen-activated protein kinase signaling, inhibits nociceptor excitability, and reduces pain hypersensitivity in mice

Directory of Open Access Journals (Sweden)

Galo L. Mejia

2016-07-01

Full Text Available Abstract. There is a great need for new therapeutics for the treatment of pain. A possible avenue to development of such therapeutics is to interfere with signaling pathways engaged in peripheral nociceptors that cause these neurons to become hyperexcitable. There is strong evidence that mitogen-activated protein kinases and phosphoinositide 3-kinase (PI3K/mechanistic target of rapamycin signaling pathways are key modulators of nociceptor excitability in vitro and in vivo. Activation of adenosine monophosphate-activated protein kinase (AMPK can inhibit signaling in both of these pathways, and AMPK activators have been shown to inhibit nociceptor excitability and pain hypersensitivity in rodents. R419 is one of, if not the most potent AMPK activator described to date. We tested whether R419 activates AMPK in dorsal root ganglion (DRG neurons and if this leads to decreased pain hypersensitivity in mice. We find that R419 activates AMPK in DRG neurons resulting in decreased mitogen-activated protein kinase signaling, decreased nascent protein synthesis, and enhanced P body formation. R419 attenuates nerve growth factor (NGF-induced changes in excitability in DRG neurons and blocks NGF-induced mechanical pain amplification in vivo. Moreover, locally applied R419 attenuates pain hypersensitivity in a model of postsurgical pain and blocks the development of hyperalgesic priming in response to both NGF and incision. We conclude that R419 is a promising lead candidate compound for the development of potent and specific AMPK activation to inhibit pain hypersensitivity as a result of injury.

Well below 2 °C: Mitigation strategies for avoiding dangerous to catastrophic climate changes

Science.gov (United States)

Xu, Yangyang; Ramanathan, Veerabhadran

2017-09-01

The historic Paris Agreement calls for limiting global temperature rise to “well below 2 °C.” Because of uncertainties in emission scenarios, climate, and carbon cycle feedback, we interpret the Paris Agreement in terms of three climate risk categories and bring in considerations of low-probability (5%) high-impact (LPHI) warming in addition to the central (˜50% probability) value. The current risk category of dangerous warming is extended to more categories, which are defined by us here as follows: >1.5 °C as dangerous; >3 °C as catastrophic; and >5 °C as unknown, implying beyond catastrophic, including existential threats. With unchecked emissions, the central warming can reach the dangerous level within three decades, with the LPHI warming becoming catastrophic by 2050. We outline a three-lever strategy to limit the central warming below the dangerous level and the LPHI below the catastrophic level, both in the near term (pollutant (SP) lever to mitigate short-lived climate pollutants, and the carbon extraction and sequestration (CES) lever to thin the atmospheric CO2 blanket. Pulling on both CN and SP levers and bending the emissions curve by 2020 can keep the central warming below dangerous levels. To limit the LPHI warming below dangerous levels, the CES lever must be pulled as well to extract as much as 1 trillion tons of CO2 before 2100 to both limit the preindustrial to 2100 cumulative net CO2 emissions to 2.2 trillion tons and bend the warming curve to a cooling trend.

The safety of Ignalina NPP and ecological danger in public opinion of inhabitants of Daugavpils region

International Nuclear Information System (INIS)

Peipinia, O.

1998-01-01

Inquest of Daugavpils' region pointed to a big anxiety for ecological danger of Ignalina NPP by inhabitants and experts. Absolute majority of respondents (73-78% inhabitants and 68-82% experts) apprehend the NPP as very dangerous and dangerous. More than half of respondents apprehend the dangerous increased during last two-three years. It is because no one has a good reference about situation, because tragic al Chernobyl NPP burst was on. The anxiety increases if the respondent lives nearer of NPP. Inhabitants of Daugavpils and it's region wants the better reference about situation, about future of Ignalina NPP after 2010 year, about securities means in case of NPP burst. (author)

Modeling human behaviors and reactions under dangerous environment.

Science.gov (United States)

Kang, J; Wright, D K; Qin, S F; Zhao, Y

2005-01-01

This paper describes the framework of a real-time simulation system to model human behavior and reactions in dangerous environments. The system utilizes the latest 3D computer animation techniques, combined with artificial intelligence, robotics and psychology, to model human behavior, reactions and decision making under expected/unexpected dangers in real-time in virtual environments. The development of the system includes: classification on the conscious/subconscious behaviors and reactions of different people; capturing different motion postures by the Eagle Digital System; establishing 3D character animation models; establishing 3D models for the scene; planning the scenario and the contents; and programming within Virtools Dev. Programming within Virtools Dev is subdivided into modeling dangerous events, modeling character's perceptions, modeling character's decision making, modeling character's movements, modeling character's interaction with environment and setting up the virtual cameras. The real-time simulation of human reactions in hazardous environments is invaluable in military defense, fire escape, rescue operation planning, traffic safety studies, and safety planning in chemical factories, the design of buildings, airplanes, ships and trains. Currently, human motion modeling can be realized through established technology, whereas to integrate perception and intelligence into virtual human's motion is still a huge undertaking. The challenges here are the synchronization of motion and intelligence, the accurate modeling of human's vision, smell, touch and hearing, the diversity and effects of emotion and personality in decision making. There are three types of software platforms which could be employed to realize the motion and intelligence within one system, and their advantages and disadvantages are discussed.

A method for the quantification of biased signalling at constitutively active receptors.

Science.gov (United States)

Hall, David A; Giraldo, Jesús

2018-06-01

Biased agonism, the ability of an agonist to differentially activate one of several signal transduction pathways when acting at a given receptor, is an increasingly recognized phenomenon at many receptors. The Black and Leff operational model lacks a way to describe constitutive receptor activity and hence inverse agonism. Thus, it is impossible to analyse the biased signalling of inverse agonists using this model. In this theoretical work, we develop and illustrate methods for the analysis of biased inverse agonism. Methods were derived for quantifying biased signalling in systems that demonstrate constitutive activity using the modified operational model proposed by Slack and Hall. The methods were illustrated using Monte Carlo simulations. The Monte Carlo simulations demonstrated that, with an appropriate experimental design, the model parameters are 'identifiable'. The method is consistent with methods based on the measurement of intrinsic relative activity (RA i ) (ΔΔlogR or ΔΔlog(τ/K a )) proposed by Ehlert and Kenakin and their co-workers but has some advantages. In particular, it allows the quantification of ligand bias independently of 'system bias' removing the requirement to normalize to a standard ligand. In systems with constitutive activity, the Slack and Hall model provides methods for quantifying the absolute bias of agonists and inverse agonists. This provides an alternative to methods based on RA i and is complementary to the ΔΔlog(τ/K a ) method of Kenakin et al. in systems where use of that method is inappropriate due to the presence of constitutive activity. © 2018 The British Pharmacological Society.

Signaling pathways activation profiles make better markers of cancer than expression of individual genes

OpenAIRE

Borisov, Nikolay M.; Terekhanova, Nadezhda V.; Aliper, Alexander M.; Venkova, Larisa S.; Smirnov, Philip Yu; Roumiantsev, Sergey; Korzinkin, Mikhail B.; Zhavoronkov, Alex A.; Buzdin, Anton A.

2014-01-01

Identification of reliable and accurate molecular markers remains one of the major challenges of contemporary biomedicine. We developed a new bioinformatic technique termed OncoFinder that for the first time enables to quantatively measure activation of intracellular signaling pathways basing on transcriptomic data. Signaling pathways regulate all major cellular events in health and disease. Here, we showed that the Pathway Activation Strength (PAS) value itself may serve as the biomarker for...

Proof-testing strategies induced by dangerous detected failures of safety-instrumented systems

International Nuclear Information System (INIS)

Liu, Yiliu; Rausand, Marvin

2016-01-01

Some dangerous failures of safety-instrumented systems (SISs) are detected almost immediately by diagnostic self-testing as dangerous detected (DD) failures, whereas other dangerous failures can only be detected by proof-testing, and are therefore called dangerous undetected (DU) failures. Some items may have a DU- and a DD-failure at the same time. After the repair of a DD-failure is completed, the maintenance team has two options: to perform an insert proof test for DU-failure or not. If an insert proof test is performed, it is necessary to decide whether the next scheduled proof test should be postponed or performed at the scheduled time. This paper analyzes the effects of different testing strategies on the safety performance of a single channel of a SIS. The safety performance is analyzed by Petri nets and by approximation formulas and the results obtained by the two approaches are compared. It is shown that insert testing improves the safety performance of the channel, but the feasibility and cost of the strategy may be a hindrance to recommend insert testing. - Highlights: • Identify the tests induced by detected failures. • Model the testing strategies following DD-failures. • Propose analytical formulas for effects of strategies. • Simulate and verify the proposed models.

Assessment of Homomorphic Analysis for Human Activity Recognition from Acceleration Signals.

Science.gov (United States)

Vanrell, Sebastian Rodrigo; Milone, Diego Humberto; Rufiner, Hugo Leonardo

2017-07-03

Unobtrusive activity monitoring can provide valuable information for medical and sports applications. In recent years, human activity recognition has moved to wearable sensors to deal with unconstrained scenarios. Accelerometers are the preferred sensors due to their simplicity and availability. Previous studies have examined several \\azul{classic} techniques for extracting features from acceleration signals, including time-domain, time-frequency, frequency-domain, and other heuristic features. Spectral and temporal features are the preferred ones and they are generally computed from acceleration components, leaving the acceleration magnitude potential unexplored. In this study, based on homomorphic analysis, a new type of feature extraction stage is proposed in order to exploit discriminative activity information present in acceleration signals. Homomorphic analysis can isolate the information about whole body dynamics and translate it into a compact representation, called cepstral coefficients. Experiments have explored several configurations of the proposed features, including size of representation, signals to be used, and fusion with other features. Cepstral features computed from acceleration magnitude obtained one of the highest recognition rates. In addition, a beneficial contribution was found when time-domain and moving pace information was included in the feature vector. Overall, the proposed system achieved a recognition rate of 91.21% on the publicly available SCUT-NAA dataset. To the best of our knowledge, this is the highest recognition rate on this dataset.

Ecological model of the interprise danger of gas

International Nuclear Information System (INIS)

Sadygov, A.B.

2009-01-01

It has been looked into the basic problems for establishment of ecological model of the enterprise danger of gas. There have been established mathematical model in the base of equation of Novye-Stoks which consists of private reproductive second row differential equation system of three

Removable butterfly valve, especially for polluting and/or dangerous fluids

International Nuclear Information System (INIS)

Garrigues, J.C.

1984-01-01

This invention relates to a valve for use in systems carrying polluting, corrosive or dangerous fluids requiring the use of biological protection. The facilities concerned are those in which fluids, mainly polluting, corrosive or dangerous liquids requiring the use of various types of biological protection, are handled. This is particularly so for nuclear installations in which the equipment is surrounded by protective shields which stop the radiation and prevent radioactive gases and aerosols from spreading. The invention proposes for the present valve a high-safety leaktightness system which respects the most specifications and standards and which suppresses any dead volume inside the valve [fr

Ordinance on the transport of dangerous goods by road (SDR)

International Nuclear Information System (INIS)

1985-04-01

This Ordinance regulates the transport of dangerous goods by road and replaces a similar Ordinance of 1972. The dangerous goods are listed in Annex A and the special provisions to be complied with for their transport are contained in Annex B. Radioactive materials, categorized as Class IVb, are included in the goods covered by the Ordinance. The Ordinance which entered into force on 1 May 1985 was amended on 9 April 1987 on a minor point and on 27 November 1989 so as to provide for special training for drivers of vehicles carrying such goods. This latter amendment entered into force on 1 January 1990. (NEA) [fr

Role of adenosine 5'-monophosphate-activated protein kinase subunits in skeletal muscle mammalian target of rapamycin signaling

DEFF Research Database (Denmark)

Deshmukh, Atul S.; Treebak, Jonas Thue; Long, Yun Chau

2008-01-01

AMP-activated protein kinase (AMPK) is an important energy-sensing protein in skeletal muscle. Mammalian target of rapamycin (mTOR) mediates translation initiation and protein synthesis through ribosomal S6 kinase 1 (S6K1) and eukaryotic initiation factor 4E-binding protein 1 (4E-BP1). AMPK...... activation reduces muscle protein synthesis by down-regulating mTOR signaling, whereas insulin mediates mTOR signaling via Akt activation. We hypothesized that AMPK-mediated inhibitory effects on mTOR signaling depend on catalytic alpha2 and regulatory gamma3 subunits. Extensor digitorum longus muscle from...... (Thr37/46) (P mTOR targets, suggesting mTOR signaling is blocked by prior AMPK activation. The AICAR-induced inhibition was partly rescued...

Lindersin B from Lindernia crustacea induces neuritogenesis by activation of tyrosine kinase A/phosphatidylinositol 3 kinase/extracellular signal-regulated kinase signaling pathway.

Science.gov (United States)

Cheng, Lihong; Ye, Ying; Xiang, Lan; Osada, Hiroyuki; Qi, Jianhua

2017-01-15

Neurotrophic factors such as nerve growth factor (NGF) play important roles in nervous system. NGF is a potential therapeutic drug for treatment of neurodegenerative diseases. However, because of physicochemical property, NGF cannot pass through the blood-brain barrier (BBB). Hence, small molecules which exhibit NGF-mimic activity and can pass through the BBB are considered to be promising drug candidates for treatment of such diseases. The present study was designed to isolate NGF-mimic substance from extract of natural products, determine their structures and investigate mechanism of action of the active substance. Extract of Lindernia crustacean was partitioned between water and ethyl acetate to obtain water layer and ethyl acetate layer samples, respectively, and then evaluated their neuritogenic activity in PC12 cells. The active sample was separated by open columns, followed by HPLC purification to obtain active compound. Then, specific inhibitors were used to investigate signaling pathway of neurite outgrowth induced by the active compound. Finally, western blot analysis was performed to confirm the pathway proposed by inhibitor experiments. The ethyl acetate layer sample of extract of Lindernia crustacea exhibited significant neuritogenic activity. Two new compounds, named as linderside A and lindersin B, were isolated; their structures were elucidated by spectroscopic and chemical derivatization methods. Linderside A is a cucurbitane glycoside, whereas lindersin B is a cucurbitane triterpenoid. Each compound has an unusual isopentene unit, namely, a double bond bound to an unmodified isopropyl group at the end of cucurbitane triterpenoid side chain. Among them, lindersin B induced significant neurite outgrowth in PC12 cells, while linderside A was inactive against PC12 cells. Western blotting analysis results showed that lindersin B-induced neuritogenic activity depended on the activation of the mitogen-activated protein kinase (MAPK)/extracellular signal

CLICs-dependent chloride efflux is an essential and proximal upstream event for NLRP3 inflammasome activation.

Science.gov (United States)

Tang, Tiantian; Lang, Xueting; Xu, Congfei; Wang, Xiaqiong; Gong, Tao; Yang, Yanqing; Cui, Jun; Bai, Li; Wang, Jun; Jiang, Wei; Zhou, Rongbin

2017-08-04

The NLRP3 inflammasome can sense different pathogens or danger signals, and has been reported to be involved in the development of many human diseases. Potassium efflux and mitochondrial damage are both reported to mediate NLRP3 inflammasome activation, but the underlying, orchestrating signaling events are still unclear. Here we show that chloride intracellular channels (CLIC) act downstream of the potassium efflux-mitochondrial reactive oxygen species (ROS) axis to promote NLRP3 inflammasome activation. NLRP3 agonists induce potassium efflux, which causes mitochondrial damage and ROS production. Mitochondrial ROS then induces the translocation of CLICs to the plasma membrane for the induction of chloride efflux to promote NEK7-NLRP3 interaction, inflammasome assembly, caspase-1 activation, and IL-1β secretion. Thus, our results identify CLICs-dependent chloride efflux as an essential and proximal upstream event for NLRP3 activation.The NLRP3 inflammasome is key to the regulation of innate immunity against pathogens or stress, but the underlying signaling regulation is still unclear. Here the authors show that chloride intracellular channels (CLIC) interface between mitochondria stress and inflammasome activation to modulate inflammatory responses.

Peroxisome Proliferator-Activated Receptor and Vitamin D Receptor Signaling Pathways in Cancer Cells

Directory of Open Access Journals (Sweden)

Yasuko Kitagishi

2013-10-01

Full Text Available Peroxisome proliferator-activated receptors (PPARs are members of the superfamily of nuclear hormone receptors, which respond to specific ligands such as polyunsaturated fatty acids by altering gene expression. Three subtypes of this receptor have been discovered, each evolving to achieve different biological functions. Like other nuclear receptors, the transcriptional activity of PPARs is affected not only by ligand-stimulation, but also by cross-talk with other molecules. For example, both PPARs and the RXRs are ligand-activated transcription factors that coordinately regulate gene expression. In addition, PPARs and vitamin D receptor (VDR signaling pathways regulate a multitude of genes that are of importance for cellular functions including cell proliferation and cell differentiation. Interaction of the PPARs and VDR signaling pathways has been shown at the level of molecular cross-regulation of their transcription factor. A variety of ligands influencing the PPARs and VDR signaling pathways have been shown to reveal chemopreventive potential by mediating tumor suppressive activities in human cancers. Use of these compounds may represent a potential novel strategy to prevent cancers. This review summarizes the roles of the PPARs and the VDR in pathogenesis and progression of cancer.

Peroxisome Proliferator-Activated Receptor and Vitamin D Receptor Signaling Pathways in Cancer Cells

Energy Technology Data Exchange (ETDEWEB)

Matsuda, Satoru, E-mail: smatsuda@cc.nara-wu.ac.jp; Kitagishi, Yasuko [Department of Food Science and Nutrition, Nara Women’s University, Kita-Uoya Nishimachi, Nara 630-8506 (Japan)

2013-10-21

Peroxisome proliferator-activated receptors (PPARs) are members of the superfamily of nuclear hormone receptors, which respond to specific ligands such as polyunsaturated fatty acids by altering gene expression. Three subtypes of this receptor have been discovered, each evolving to achieve different biological functions. Like other nuclear receptors, the transcriptional activity of PPARs is affected not only by ligand-stimulation, but also by cross-talk with other molecules. For example, both PPARs and the RXRs are ligand-activated transcription factors that coordinately regulate gene expression. In addition, PPARs and vitamin D receptor (VDR) signaling pathways regulate a multitude of genes that are of importance for cellular functions including cell proliferation and cell differentiation. Interaction of the PPARs and VDR signaling pathways has been shown at the level of molecular cross-regulation of their transcription factor. A variety of ligands influencing the PPARs and VDR signaling pathways have been shown to reveal chemopreventive potential by mediating tumor suppressive activities in human cancers. Use of these compounds may represent a potential novel strategy to prevent cancers. This review summarizes the roles of the PPARs and the VDR in pathogenesis and progression of cancer.

Peroxisome Proliferator-Activated Receptor and Vitamin D Receptor Signaling Pathways in Cancer Cells

International Nuclear Information System (INIS)

Matsuda, Satoru; Kitagishi, Yasuko

2013-01-01

Peroxisome proliferator-activated receptors (PPARs) are members of the superfamily of nuclear hormone receptors, which respond to specific ligands such as polyunsaturated fatty acids by altering gene expression. Three subtypes of this receptor have been discovered, each evolving to achieve different biological functions. Like other nuclear receptors, the transcriptional activity of PPARs is affected not only by ligand-stimulation, but also by cross-talk with other molecules. For example, both PPARs and the RXRs are ligand-activated transcription factors that coordinately regulate gene expression. In addition, PPARs and vitamin D receptor (VDR) signaling pathways regulate a multitude of genes that are of importance for cellular functions including cell proliferation and cell differentiation. Interaction of the PPARs and VDR signaling pathways has been shown at the level of molecular cross-regulation of their transcription factor. A variety of ligands influencing the PPARs and VDR signaling pathways have been shown to reveal chemopreventive potential by mediating tumor suppressive activities in human cancers. Use of these compounds may represent a potential novel strategy to prevent cancers. This review summarizes the roles of the PPARs and the VDR in pathogenesis and progression of cancer

Vitamin D controls T cell antigen receptor signaling and activation of human T cells

DEFF Research Database (Denmark)

von Essen, Marina Rode; Kongsbak-Wismann, Martin; Schjerling, Peter

2010-01-01

Phospholipase C (PLC) isozymes are key signaling proteins downstream of many extracellular stimuli. Here we show that naive human T cells had very low expression of PLC-gamma1 and that this correlated with low T cell antigen receptor (TCR) responsiveness in naive T cells. However, TCR triggering...... led to an upregulation of approximately 75-fold in PLC-gamma1 expression, which correlated with greater TCR responsiveness. Induction of PLC-gamma1 was dependent on vitamin D and expression of the vitamin D receptor (VDR). Naive T cells did not express VDR, but VDR expression was induced by TCR...... signaling via the alternative mitogen-activated protein kinase p38 pathway. Thus, initial TCR signaling via p38 leads to successive induction of VDR and PLC-gamma1, which are required for subsequent classical TCR signaling and T cell activation....

Results of the MITRA project: Monitoring and intervention for the transportation of dangerous goods

International Nuclear Information System (INIS)

Planas, E.; Pastor, E.; Presutto, F.; Tixier, J.

2008-01-01

The objective of the MITRA (monitoring and intervention for the transportation of dangerous goods) project was to prototype a new operational system for monitoring the transportation of dangerous goods in Europe based on regional responsibilities. This concept, based on systems used in air traffic control, aims to provide civil security centres with real-time knowledge of the position and contents of dangerous vehicles circulating in their area of responsibility, and, in the event of a dangerous situation, to issue warnings, alerts and crisis management information, thereby allowing intervention teams to react immediately with maximum safety. The project was funded by the European Commission under the 6th Framework Programme (STREP - specific targeted research project - under the Information Society Technologies priority). It started on 1 September 2004 and ended on 31 October 2006. This paper presents the results of this project and the conclusions derived from the field tests carried out in Germany and in the French/Spanish border region in order to test the proposed operational system

[Dangerous comics--only a fantasy?].

Science.gov (United States)

Hammon, C P

1992-01-01

Both superhero comics and fairy tales are equally popular with children: they create fantasy worlds full of violence and dangers which the hero must overcome. The question is raised whether the criticism of prevailing violence and a lack of realism can be rejected not only when considering fairy tales but also in the case of comics. The comparison of the two genres leads to the following results: Comics with their regressive pull and their independent superhuman heroes represent the archaic world of narcissism unconscious, unwilling to develop and conservative. Violence serves to maintain the original state or regain a harmonious "paradise". However, the rich world of symbols is also the creative source of our existence to which we keep returning--whether in dreams or in other fields of imagination. As works of literature, fairy tales seem to be more progressive and concerned with solutions. In the main, they support the development of the self. Violence is used to overthrow the old order and usher in the new. The aggression results in overcoming the unconscious. The image of the fairy tale hero corresponds to the child's view of the world. He does not seek narcissistic solitude and greatness but the companionship of prince or princess. A progressive and optimistic view of the future as well as a more conservative and retrospective tendency are part of human nature. For children, however, problems of development take precedence. Thus superhero comics are only dangerous for severely disturbed children, but fairy tales are certainly more beneficial.

E3 Ubiquitin Ligase RNF125 Activates Interleukin-36 Receptor Signaling and Contributes to Its Turnover.

Science.gov (United States)

Saha, Siddhartha S; Caviness, Gary; Yi, Guanghui; Raymond, Ernest L; Mbow, M Lamine; Kao, C Cheng

2018-01-01

Signaling by the interleukin-36 receptor (IL-36R) is linked to inflammatory diseases such as psoriasis. However, the regulation of IL-36R signaling is poorly understood. Activation of IL-36R signaling in cultured cells results in an increased polyubiquitination of the receptor subunit, IL-1Rrp2. Treatment with deubiquitinases shows that the receptor subunit of IL-36R, IL-1Rrp2, is primarily polyubiquitinated at the K63 position, which is associated with endocytic trafficking and signal transduction. A minor amount of ubiquitination is at the K48 position that is associated with protein degradation. A focused siRNA screen identified RNF125, an E3 ubiquitin ligase, to ubiquitinate IL-1Rrp2 upon activation of IL-36R signaling while not affecting the activated IL-1 receptor. Knockdown of RNF125 decreases signal transduction by the IL-36R. Overexpression of RNF125 in HEK293T cells activates IL-36R signaling and increases the ubiquitination of IL-1Rrp2 and its subsequent turnover. RNF125 can coimmunoprecipitate with the IL-36R, and it traffics with IL-1Rrp2 from the cell surface to lysosomes. Mutations of Lys568 and Lys569 in the C-terminal tail of IL-1Rrp2 decrease ubiquitination by RNF125 and increase the steady-state levels of IL-1Rrp2. These results demonstrate that RNF125 has multiple regulatory roles in the signaling, trafficking, and turnover of the IL-36R. © 2017 S. Karger AG, Basel.

By-law from December 6, 1996 relative to the rail transport of dangerous goods (called ''RID by-law''). (Dangerous materials no. 2)

International Nuclear Information System (INIS)

Mesnil, H. du

1996-01-01

The aim of this by-law from the French ministry of equipment, lodging, transports and tourism is to define the specific rules that must be applied in France to the national or international rail transport of dangerous freight (radioactive materials, explosive materials, under pressure compressed, liquefied or dissolved gases, flammable liquids and solids, spontaneously flammable materials, combustive agents, organic peroxides, noxious, infectious and corrosive materials etc..). The classification of dangerous materials and the freight that cannot be transported by train is listed in two appendixes [700 p.] at the end of the document. This by-law gives the rules concerning: the building, testing, agreement, labelling, periodical controls and conditions for use of packing materials, drums, containers and tank wagons; the equipments, the loading and unloading, the running and parking of wagons; the documents relative to the transport. (J.S.)

Chemical industrial areas and their dynamic danger behaviour

NARCIS (Netherlands)

Reniers, Genserik L L; Audenaert, Amaryllis; Dullaert, W.; Soudan, K.

2007-01-01

Chemical industrial areas or so-called chemical clusters consist of various companies situated next to each other. Such areas are composed of hundreds of chemical installations exhibiting danger to a certain degree for initiating or continuing knock-on effects. In this paper, a methodology to model

Hanford facility dangerous waste permit application, general information portion

International Nuclear Information System (INIS)

Hays, C.B.

1998-01-01

The Hanford Facility Dangerous Waste Permit Application is considered to be a single application organized into a General Information Portion (document number DOE/RL-91-28) and a Unit-Specific Portion. Both the General Information and Unit-Specific portions of the Hanford Facility Dangerous Waste Permit Application address the content of the Part B permit application guidance prepared by the Washington State Department of Ecology (Ecology 1996) and the U.S. Environmental Protection Agency (40 Code of Federal Regulations 270), with additional information needed by the Hazardous and Solid Waste Amendments and revisions of Washington Administrative Code 173-303. Documentation contained in the General Information Portion is broader in nature and could be used by multiple treatment, storage, and/or disposal units (e.g., the glossary provided in this report)

Low-Level Burial Grounds Dangerous Waste Permit Application

International Nuclear Information System (INIS)

1989-01-01

The single dangerous waste permit identification number issued to the Hanford Site by the US Environmental Protection Agency and the Washington State Department of Ecology is US Environmental Protection Agency/State Identification Number WA 7890008967. This identification number encompasses a number of waste management units within the Hanford Site. Westinghouse Hanford Company is a major contractor to the US Department of Energy-Richland Operations Office and serves as co-operator of the Low-Level Burial Grounds, the waste management unit addressed by this permit application. The Low-Level Burial Grounds Dangerous Waste Permit Application consists of both a Part A and a Part B Permit Application. The original Part A, submitted in November 1985, identified landfills, retrievable storage units, and reserved areas. An explanation of subsequent Part A revisions is provided at the beginning of the Part A section. Part B consists of 15 chapters addressing the organization and content of the Part B checklist prepared by the Washington State Department of Ecology

Polysaccharides and their depolymerized fragments from Costaria costata: Molecular weight and sulfation-dependent anticoagulant and FGF/FGFR signal activating activities.

Science.gov (United States)

Hou, Ningning; Zhang, Meng; Xu, Yingjie; Sun, Zhongmin; Wang, Jing; Zhang, Lijuan; Zhang, Quanbin

2017-12-01

Crude polysaccharides from Costaria costata were extracted by hot water and further fractionated by anion exchange chromatography into three polysaccharide fractions. Three low molecular weight fragments were then prepared by degradation of the polysaccharides with hydrogen peroxide and ascorbic acid. The structural features of the polysaccharides and their low molecular weight fragments were elucidated for the first time based on the HGPC, FT-IR, NMR, MS, monosaccharide composition, and other chemical analyses. Their anticoagulant and FGF-1, -2, -7, -8, -9, -10/FGFR1c signaling activation activities in BaF3 cells were also examined. Our studies showed that the polysaccharides were sulfated at different positions of galactose and fucose residues. The APTT-, PT- and TT-based anticoagulant assay results indicated that a high molecular weight and a higher degree of sulfation were essential for their anticoagulant activities. In contrast, not only the polysaccharides but also the depolymerized fragments showed significant FGF/FGFR signal activating activities in a FGF-, molecular weight-, and sulfation-dependent manner. The results presented in current study demonstrated the potential use of the polysaccharides and their fragments as anticoagulants and FGF signal regulators. Copyright © 2017 Elsevier B.V. All rights reserved.

Civil liability on nuclear activities

International Nuclear Information System (INIS)

Bittar, C.A.

1982-01-01

The civil liability theory in the actual context is shown in the first and second part of this thesis, including some considerations about concepts and types of liability in dangerous and not dangerous activities. In the third part, the legal aspects of civil liability for the nuclear activities are analyzed, with a brief description of the history evolution, standard systems, inspection corporation and juridical regulation. (C.G.C.). 239 refs

Design of excitation signals for active system monitoring in a performance assessment setup

DEFF Research Database (Denmark)

Green, Torben; Izadi-Zamanabadi, Roozbeh; Niemann, Hans Henrik

2011-01-01

This paper investigates how the excitation signal should be chosen for a active performance setup. The signal is used in a setup where the main purpose is to detect whether a parameter change of the controller has changed the global performance significantly. The signal has to be able to excite...... the dynamics of the subsystem under investigation both before and after the parameter change. The controller is well know, but there exists no detailed knowledge about the dynamics of the subsystem....

Hyaluronan activates Hyal-2/WWOX/Smad4 signaling and causes bubbling cell death when the signaling complex is overexpressed.

Science.gov (United States)

Hsu, Li-Jin; Hong, Qunying; Chen, Shur-Tzu; Kuo, Hsiang-Lin; Schultz, Lori; Heath, John; Lin, Sing-Ru; Lee, Ming-Hui; Li, Dong-Zhang; Li, Zih-Ling; Cheng, Hui-Ching; Armand, Gerard; Chang, Nan-Shan

2017-03-21

Malignant cancer cells frequently secrete significant amounts of transforming growth factor beta (TGF-β), hyaluronan (HA) and hyaluronidases to facilitate metastasizing to target organs. In a non-canonical signaling, TGF-β binds membrane hyaluronidase Hyal-2 for recruiting tumor suppressors WWOX and Smad4, and the resulting Hyal-2/WWOX/Smad4 complex is accumulated in the nucleus to enhance SMAD-promoter dependent transcriptional activity. Yeast two-hybrid analysis showed that WWOX acts as a bridge to bind both Hyal-2 and Smad4. When WWOX-expressing cells were stimulated with high molecular weight HA, an increased formation of endogenous Hyal-2/WWOX/Smad4 complex occurred rapidly, followed by relocating to the nuclei in 20-40 min. In WWOX-deficient cells, HA failed to induce Smad2/3/4 relocation to the nucleus. To prove the signaling event, we designed a real time tri-molecular FRET analysis and revealed that HA induces the signaling pathway from ectopic Smad4 to WWOX and finally to p53, as well as from Smad4 to Hyal-2 and then to WWOX. An increased binding of the Smad4/Hyal-2/WWOX complex occurs with time in the nucleus that leads to bubbling cell death. In contrast, HA increases the binding of Smad4/WWOX/p53, which causes membrane blebbing but without cell death. In traumatic brain injury-induced neuronal death, the Hyal-2/WWOX complex was accumulated in the apoptotic nuclei of neurons in the rat brains in 24 hr post injury, as determined by immunoelectron microscopy. Together, HA activates the Hyal-2/WWOX/Smad4 signaling and causes bubbling cell death when the signaling complex is overexpressed.

Notch signaling activation in human embryonic stem cells is required for embryonic but not trophoblastic lineage commitment

OpenAIRE

Yu, Xiaobing; Zou, Jizhong; Ye, Zhaohui; Hammond, Holly; Chen, Guibin; Tokunaga, Akinori; Mali, Prashant; Li, Yue-Ming; Civin, Curt; Gaiano, Nicholas; Cheng, Linzhao

2008-01-01

The Notch signaling pathway plays important roles in cell fate determination during embryonic development and adult life. In this study, we focus on the role of Notch signaling in governing cell fate choices in human embryonic stem (hES) cells. Using genetic and pharmacological approaches, we achieved both blockade and conditional activation of Notch signaling in several hES cell lines. We report here that activation of Notch signaling is required for undifferentiated hES cells to form the pr...

New valve with remote control and dismantling for polluting and dangerous fluid

International Nuclear Information System (INIS)

Villepreux, Robert.

1980-01-01

This invention relates to a valve for use in systems carrying polluting, corrosive or dangerous fluids requiring the use of biological protection. The facilities concerned are those in which fluids, mainly polluting, corrosive or dangerous liquids requiring the use of various types of biological protection, are handled. This is particularly so for nuclear installations in which the equipment is surrounded by protective shields which stop the radiation and prevent radioactive gases and aerosols from spreading [fr

Is nuclear energy power generation more dangerous than power generation by wind and solar energy

Energy Technology Data Exchange (ETDEWEB)

Ding, Y

1979-03-01

Since the occurrence of the petroleum crisis, many countries have devoted a great deal of effort to search for substitute energy sources. Aside from nuclear energy, forms of power generation with wind, solar energy, and geothermal energy have all been actually adopted in one place or another. Most recently, a research report was published by the Canadian Bureau of Nuclear Energy Management stating that the use of wind and solar energy to generate electricity is much more dangerous than power generation with nuclear energy. When mining, transportation, machine manufacturing, etc. are included in the process of producing unit power, i.e. kilowatt/year, the data of various risks of death, injury, and diseases are computed in terms of man/day losses by the bureau. They indicate that of the ten forms of power generation, the danger is the least with natural gas, only about a 6 man/day, and nuclear energy is the next least dangerous, about 10 man/day. The danger of using temperature differential of sea water to generate electricity is about 25 man/day, and the most dangerous form of power generation is coal, amounting to three thousand man/day.

Ministerial Order of 22 August 1957 on the transport of dangerous materials by air

International Nuclear Information System (INIS)

1957-01-01

This Order provides for the conditions of transport of dangerous materials by air. Materials regarded as dangerous to handle or transport by aircraft from a safety or health standpoint may possibly not be accepted, or only accepted under certain conditions. These materials include radioactive materials in Class IV(b). (NEA) [fr

Signal detection by active, noisy hair bundles

Science.gov (United States)

O'Maoiléidigh, Dáibhid; Salvi, Joshua D.; Hudspeth, A. J.

2018-05-01

Vertebrate ears employ hair bundles to transduce mechanical movements into electrical signals, but their performance is limited by noise. Hair bundles are substantially more sensitive to periodic stimulation when they are mechanically active, however, than when they are passive. We developed a model of active hair-bundle mechanics that predicts the conditions under which a bundle is most sensitive to periodic stimulation. The model relies only on the existence of mechanotransduction channels and an active adaptation mechanism that recloses the channels. For a frequency-detuned stimulus, a noisy hair bundle's phase-locked response and degree of entrainment as well as its detection bandwidth are maximized when the bundle exhibits low-amplitude spontaneous oscillations. The phase-locked response and entrainment of a bundle are predicted to peak as functions of the noise level. We confirmed several of these predictions experimentally by periodically forcing hair bundles held near the onset of self-oscillation. A hair bundle's active process amplifies the stimulus preferentially over the noise, allowing the bundle to detect periodic forces less than 1 pN in amplitude. Moreover, the addition of noise can improve a bundle's ability to detect the stimulus. Although, mechanical activity has not yet been observed in mammalian hair bundles, a related model predicts that active but quiescent bundles can oscillate spontaneously when they are loaded by a sufficiently massive object such as the tectorial membrane. Overall, this work indicates that auditory systems rely on active elements, composed of hair cells and their mechanical environment, that operate on the brink of self-oscillation.

Detecting danger labels with RAM-based neural networks

DEFF Research Database (Denmark)

Jørgensen, T.M.; Christensen, S.S.; Andersen, A.W.

1996-01-01

An image processing system for the automatic location of danger labels on the back of containers is presented. The system uses RAM-based neural networks to locate and classify labels after a pre-processing step involving specially designed non-linear edge filters and RGB-to-HSV conversion. Result...

Uric Acid Induces Renal Inflammation via Activating Tubular NF-κB Signaling Pathway

Science.gov (United States)

Zhou, Yang; Fang, Li; Jiang, Lei; Wen, Ping; Cao, Hongdi; He, Weichun; Dai, Chunsun; Yang, Junwei

2012-01-01

Inflammation is a pathologic feature of hyperuricemia in clinical settings. However, the underlying mechanism remains unknown. Here, infiltration of T cells and macrophages were significantly increased in hyperuricemia mice kidneys. This infiltration of inflammatory cells was accompanied by an up-regulation of TNF-α, MCP-1 and RANTES expression. Further, infiltration was largely located in tubular interstitial spaces, suggesting a role for tubular cells in hyperuricemia-induced inflammation. In cultured tubular epithelial cells (NRK-52E), uric acid, probably transported via urate transporter, induced TNF-α, MCP-1 and RANTES mRNA as well as RANTES protein expression. Culture media of NRK-52E cells incubated with uric acid showed a chemo-attractive ability to recruit macrophage. Moreover uric acid activated NF-κB signaling. The uric acid-induced up-regulation of RANTES was blocked by SN 50, a specific NF-κB inhibitor. Activation of NF-κB signaling was also observed in tubule of hyperuricemia mice. These results suggest that uric acid induces renal inflammation via activation of NF-κB signaling. PMID:22761883

Who is a dangerous driver? Socio-demographic and personal determinants of risky traffic behavior

Directory of Open Access Journals (Sweden)

Aleksandra Peplińska

2015-08-01

Full Text Available Background The aim of this study was to search for comprehensive socio-demographic and personal (personality and temperamental determinants of risky on-the-road behavior. Based on the results of previous studies, we assumed that the main predictors of dangerous traffic behavior include: internal locus of control, sensation seeking, risk seeking and risk acceptance, as well as high self-esteem, a low level of reactivity combined with a high level of endurance and activity (which together determine a strong need for stimulation and a preference for hedonistic values; and among socio-demographic variables – age, gender, education and duration of having a driving license. Participants and procedure The study included a group of 380 participants, aged between 19 and 61 years (Me = 24. In order to verify the hypothesis, a battery of research tools measuring personality and temperamental variables was adopted, namely: the Formal Characteristics of Behavior – Temperament Questionnaire, Rotter I-E Scale, Risk Acceptance Scale, Stimulating-Instrumental Risk Inventory, Scheler Value Scale, Zuckerman Sensation Seeking Scale and Rosenberg Self-Esteem Scale. Results The dangerous driver syndrome was found to be promoted by high levels of experience and sensation seeking, low levels of tolerance to boredom and monotony, high need for stimulating risk and high risk acceptance, high self-esteem, a preference for hedonistic values coupled with aversion towards moral values, as well as low sensory sensitivity, and was especially visible among older men with short driving experience. Conclusions It can be concluded that both socio-demographic and psychological variables, such as temperament and personality, are significant predictors of dangerous traffic behavior.

The kinase activity of the Ser/Thr kinase BUB1 promotes TGF-β signaling.

Science.gov (United States)

Nyati, Shyam; Schinske-Sebolt, Katrina; Pitchiaya, Sethuramasundaram; Chekhovskiy, Katerina; Chator, Areeb; Chaudhry, Nauman; Dosch, Joseph; Van Dort, Marcian E; Varambally, Sooryanarayana; Kumar-Sinha, Chandan; Nyati, Mukesh Kumar; Ray, Dipankar; Walter, Nils G; Yu, Hongtao; Ross, Brian Dale; Rehemtulla, Alnawaz

2015-01-06

Transforming growth factor-β (TGF-β) signaling regulates cell proliferation and differentiation, which contributes to development and disease. Upon binding TGF-β, the type I receptor (TGFBRI) binds TGFBRII, leading to the activation of the transcription factors SMAD2 and SMAD3. Using an RNA interference screen of the human kinome and a live-cell reporter for TGFBR activity, we identified the kinase BUB1 (budding uninhibited by benzimidazoles-1) as a key mediator of TGF-β signaling. BUB1 interacted with TGFBRI in the presence of TGF-β and promoted the heterodimerization of TGFBRI and TGFBRII. Additionally, BUB1 interacted with TGFBRII, suggesting the formation of a ternary complex. Knocking down BUB1 prevented the recruitment of SMAD3 to the receptor complex, the phosphorylation of SMAD2 and SMAD3 and their interaction with SMAD4, SMAD-dependent transcription, and TGF-β-mediated changes in cellular phenotype including epithelial-mesenchymal transition (EMT), migration, and invasion. Knockdown of BUB1 also impaired noncanonical TGF-β signaling mediated by the kinases AKT and p38 MAPK (mitogen-activated protein kinase). The ability of BUB1 to promote TGF-β signaling depended on the kinase activity of BUB1. A small-molecule inhibitor of the kinase activity of BUB1 (2OH-BNPP1) and a kinase-deficient mutant of BUB1 suppressed TGF-β signaling and formation of the ternary complex in various normal and cancer cell lines. 2OH-BNPP1 administration to mice bearing lung carcinoma xenografts reduced the amount of phosphorylated SMAD2 in tumor tissue. These findings indicated that BUB1 functions as a kinase in the TGF-β pathway in a role beyond its established function in cell cycle regulation and chromosome cohesion. Copyright © 2015, American Association for the Advancement of Science.

Can Co-Activation of Nrf2 and Neurotrophic Signaling Pathway Slow Alzheimer’s Disease?

Directory of Open Access Journals (Sweden)

Kelsey E. Murphy

2017-05-01

Full Text Available Alzheimer’s disease (AD is a multifaceted disease that is hard to treat by single-modal treatment. AD starts with amyloid peptides, mitochondrial dysfunction, and oxidative stress and later is accompanied with chronic endoplasmic reticulum (ER stress and autophagy dysfunction, resulting in more complicated pathogenesis. Currently, few treatments can modify the complicated pathogenic progress of AD. Compared to the treatment with exogenous antioxidants, the activation of global antioxidant defense system via Nrf2 looks more promising in attenuating oxidative stress in AD brains. Accompanying the activation of the Nrf2-mediated antioxidant defense system that reduce the AD-causative factor, oxidative stress, it is also necessary to activate the neurotrophic signaling pathway that replaces damaged organelles and molecules with new ones. Thus, the dual actions to activate both the Nrf2 antioxidant system and neurotrophic signaling pathway are expected to provide a better strategy to modify AD pathogenesis. Here, we review the current understanding of AD pathogenesis and neuronal defense systems and discuss a possible way to co-activate the Nrf2 antioxidant system and neurotrophic signaling pathway with the hope of helping to find a better strategy to slow AD.

Brain injury and discrimination: Two competing models-perceptions of responsibility and dangerousness.

Science.gov (United States)

Foster, Lynette A; Leathem, Janet M; Humphries, Steve

2016-01-01

(1) To examine whether the willingness of people to socialize with adolescents with brain injury is influenced by gender, visibility of injury and/or knowing how to interact with people with brain injury; and (2) To consider two models: the responsibility model (attributions about the cause of a condition) and the danger appraisal model (perceptions of dangerousness due to anger/aggression) for their effect on willingness to socialize and to understand how these perceptions lead to avoidant behaviour. Participants were recruited either by personal approach or via Facebook advertising and completed a survey after reading a brief vignette and seeing a photo of an adolescent male or female, with or without a head scar. Vignettes for some participants were varied to represent perceptions of responsibility and dangerousness Main outcomes and results: ANOVAs and structural equation modelling revealed that participants were more willing to socialize with the adolescents with a scar than with no scar. Knowledge about how to interact with survivors impacted willingness to socialize, but familiarity did not. The full danger appraisal model was supported, but only some aspects of the responsibility model were supported. The results provide useful information for rehabilitation health professionals working with survivors of brain injury. The implications of these findings are discussed with regards to assisting adolescents' re-entry into society post-injury.

Dangerous universal donors: the reality of the Hemocentro in Belo Horizonte, Minas Gerais

Directory of Open Access Journals (Sweden)

Mariana Martins Godin

Full Text Available ABSTRACT BACKGROUND: The term dangerous universal blood donor refers to potential agglutination of the erythrocytes of non-O recipients due to plasma of an O blood group donor, which contains high titers of anti-A and/or anti-B hemagglutinins. Thus, prior titration of anti-A and anti-B hemagglutinins is recommended to prevent transfusion reactions. OBJECTIVE: The aim of this study was to estimate the frequency of dangerous universal donors in the blood bank of Belo Horizonte (Fundação Central de Imuno-Hematologia - Fundação Hemominas - Minas Gerais by determining the titers of anti-A and anti-B hemagglutinins in O blood group donors. METHOD: A total of 400 O blood group donors were randomly selected, from March 2014 to January 2015. The titers of anti-A and anti-B hemagglutinins (IgM and IgG classes were obtained using the tube titration technique. Dangerous donors were those whose titers of anti-A or anti-B IgM were ≥128 and/or the titers of anti-A or anti-B IgG were ≥256. Donors were characterized according to gender, age and ethnicity. The hemagglutinins were characterized by specificity (anti-A and anti-B and antibody class (IgG and IgM. RESULTS: Almost one-third (30.5% of the O blood group donors were universal dangerous. The frequency among women was higher than that of men (p-value = 0.019; odds ratio: 1.66; 95% confidence interval: 1.08-2.56 and among young donors (18-29 years old it was higher than for donors between 49 and 59 years old (p-value = 0.015; odds ratio: 3.05; 95% confidence interval: 1.22-7.69. There was no significant association between dangerous universal donors and ethnicity, agglutinin specificity or antibody class. CONCLUSION: Especially platelet concentrates obtained by apheresis (that contain a substantial volume of plasma, coming from dangerous universal donors should be transfused in isogroup recipients whenever possible in order to prevent the occurrence of transfusion reactions.

Recordings of mucociliary activity in vivo: benefit of fast Fourier transformation of the photoelectric signal.

Science.gov (United States)

Lindberg, S; Cervin, A; Runer, T; Thomasson, L

1996-09-01

Investigations of mucociliary activity in vivo are based on photoelectric recordings of light reflections from the mucosa. The alterations in light intensity produced by the beating cilia are picked up by a photodetector and converted to photoelectric signals. The optimal processing of these signals is not known, but in vitro recordings have been reported to benefit from fast Fourier transformation (FFT) of the signal. The aim of the investigation was to study the effect of FFT for frequency analysis of photoelectric signals originating from an artificial light source simulating mucociliary activity or from sinus or nasal mucosa in vivo, as compared to a conventional method of calculating mucociliary wave frequency, in which each peak in the signal is interpreted as a beat (old method). In the experiments with the artificial light source, the FFT system was superior to the conventional method by a factor of 50 in detecting weak signals. By using FFT signal processing, frequency could be correctly calculated in experiments with a compound signal. In experiments in the rabbit maxillary sinus, the spontaneous variations were greater when signals were processed by FFT. The correlation between the two methods was excellent: r = .92. The increase in mucociliary activity in response to the ciliary stimulant methacholine at a dosage of 0.5 microgram/kg was greater measured with the FFT than with the old method (55.3% +/- 8.3% versus 43.0% +/- 8.2%, p detected. In the human nose, recordings from aluminum foil placed on the nasal dorsum and from the nasal septa mucosa displayed some similarities in the lower frequency spectrum (light, the mean frequency in seven healthy volunteers being 7.8 +/- 1.6 Hz for the human nasal mucosa. It is concluded that the FFT system has greater sensitivity in detecting photoelectric signals derived from the mucociliary system, and that it is also a useful tool for analyzing the contributions of artifacts to the signal.

Growth-hormone-induced signal transducer and activator of transcription 5 signaling causes gigantism, inflammation, and premature death but protects mice from aggressive liver cancer.

Science.gov (United States)

Friedbichler, Katrin; Themanns, Madeleine; Mueller, Kristina M; Schlederer, Michaela; Kornfeld, Jan-Wilhelm; Terracciano, Luigi M; Kozlov, Andrey V; Haindl, Susanne; Kenner, Lukas; Kolbe, Thomas; Mueller, Mathias; Snibson, Kenneth J; Heim, Markus H; Moriggl, Richard

2012-03-01

Persistently high levels of growth hormone (GH) can cause liver cancer. GH activates multiple signal-transduction pathways, among them janus kinase (JAK) 2-signal transducer and activator of transcription (STAT) 5 (signal transducer and activator of transcription 5). Both hyperactivation and deletion of STAT5 in hepatocytes have been implicated in the development of hepatocellular carcinoma (HCC); nevertheless, the role of STAT5 in the development of HCC as a result of high GH levels remains enigmatic. Thus, we crossed a mouse model of gigantism and inflammatory liver cancer caused by hyperactivated GH signaling (GH(tg) ) to mice with hepatic deletion of STAT5 (STAT5(Δhep) ). Unlike GH(tg) mice, GH(tg) STAT5(Δhep) animals did not display gigantism. Moreover, the premature mortality, which was associated with chronic inflammation, as well as the pathologic alterations of hepatocytes observed in GH(tg) mice, were not observed in GH(tg) animals lacking STAT5. Strikingly, loss of hepatic STAT5 proteins led to enhanced HCC development in GH(tg) mice. Despite reduced chronic inflammation, GH(tg) STAT5(Δhep) mice displayed earlier and more advanced HCC than GH(tg) animals. This may be attributed to the combination of increased peripheral lipolysis, hepatic lipid synthesis, loss of hepatoprotective mediators accompanied by aberrant activation of tumor-promoting c-JUN and STAT3 signaling cascades, and accumulation of DNA damage secondary to loss of cell-cycle control. Thus, HCC was never observed in STAT5(Δhep) mice. As a result of their hepatoprotective functions, STAT5 proteins prevent progressive fatty liver disease and the formation of aggressive HCC in the setting of hyperactivated GH signaling. At the same time, they play a key role in controlling systemic inflammation and regulating organ and body size. Copyright © 2011 American Association for the Study of Liver Diseases.

DrivingSense: Dangerous Driving Behavior Identification Based on Smartphone Autocalibration

Directory of Open Access Journals (Sweden)

Chunmei Ma

2017-01-01

Full Text Available Since pervasive smartphones own advanced computing capability and are equipped with various sensors, they have been used for dangerous driving behaviors detection, such as drunk driving. However, sensory data gathered by smartphones are noisy, which results in inaccurate driving behaviors estimations. Some existing works try to filter noise from sensor readings, but usually only the outlier data are filtered. The noises caused by hardware of the smartphone cannot be removed from the sensor reading. In this paper, we propose DrivingSense, a reliable dangerous driving behavior identification scheme based on smartphone autocalibration. We first theoretically analyze the impact of the sensor error on the vehicle driving behavior estimation. Then, we propose a smartphone autocalibration algorithm based on sensor noise distribution determination when a vehicle is being driven. DrivingSense leverages the corrected sensor parameters to identify three kinds of dangerous behaviors: speeding, irregular driving direction change, and abnormal speed control. We evaluate the effectiveness of our scheme under realistic environments. The results show that DrivingSense, on average, is able to detect the driving direction change event and abnormal speed control event with 93.95% precision and 90.54% recall, respectively. In addition, the speed estimation error is less than 2.1 m/s, which is an acceptable range.

The Association of Endothelin-1 Signaling with Bone Alkaline Phosphatase Expression and Protumorigenic Activities in Canine Osteosarcoma.

Science.gov (United States)

Neumann, Z L; Pondenis, H C; Masyr, A; Byrum, M L; Wycislo, K L; Fan, T M

2015-01-01

Canine osteosarcoma (OS) is an aggressive sarcoma characterized by pathologic skeletal resorption and pulmonary metastases. A number of negative prognostic factors, including bone alkaline phosphatase, have been identified in dogs with OS, but the underlying biologic factors responsible for such observations have not been thoroughly investigated. Endothelin-1-mediated signaling is active during bone repair, and is responsible for osteoblast migration, survival, proliferation, and bone alkaline phosphatase expression. The endothelin-1 signaling axis is active in canine OS cells, and this pathway is utilized by malignant osteoblasts for promoting cellular migration, survival, proliferation, and bone alkaline phosphatase activities. 45 dogs with appendicular OS. The expressions of endothelin-1 and endothelin A receptor were studied in OS cell lines and in samples from spontaneously occurring tumors. Activities mediated by endothelin-1 signaling were investigated by characterizing responses in 3 OS cell lines. In 45 dogs with OS, bone alkaline phosphatase concentrations were correlated with primary tumor osteoproductivity. Canine OS cells express endothelin-1 and endothelin A receptor, and this signaling axis mediates OS migration, survival, proliferation, and bone alkaline phosphatase activities. In OS-bearing dogs, circulating bone alkaline phosphatase activities were positively correlated with primary tumor relative bone mineral densities. Canine OS cells express endothelin-1 and functional endothelin A receptors, with the potential for a protumorigenic signaling loop. Increases in bone alkaline phosphatase activity are associated with osteoblastic OS lesions, and might be an epiphenomenon of active endothelin-1 signaling or excessive osteoproduction within the localized bone microenvironment. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Four possible types of dangerous viruses in aerospace traces of invasions in conditions of modern hybrid wars

Science.gov (United States)

Churyumov, K. I.; Steklov, A. F.; Vidmachenko, A. P.; Dashkiev, G. N.; Steklov, E. A.; Slipchenko, A. S.; Romaniuk, Ya. O.

2016-10-01

1. Reasons for the creation of modern services of terrestrial space monitoring. In recent years, an increasingly important role in an observation of traces of invasions fireball in an Earth's atmosphere, playing artificial earth satellites at low and medium orbits. But the time between such registrations - is about one and a half hours. And consequently, many types of traces of invasions of small fragments of nuclei of comets, asteroids and meteoroids - remain outside of the data. In the interest of safety of large and medium-sized cities need to create a special small basic observatories of terrestrial aerospace monitoring services. 2. Four types of dangerous viruses that may be present in traces of all kinds of dangerous invasions into the sky over our cities. In modern times the most dangerous commonly believed the cosmic viruses in the nuclei of comets and their fragments; orbital recurrent-mutant viruses, bacteria, fungi in an components of Space Debris (for example, in the fragments of space station "Mir"); as well as modern modified and synthetic viruses, that are easy and very effective is possible to apply in the invasion of simple, and suborbital unmanned aerial vehicles, especially with the function of self-destruction, in order to the invasion able to remain latent, secret, poorly registrable. 3. Our plans on criteria experimentation for active operations with a specialized astronomical aviation of special purpose. Essence of the method according to the ideas is very simple; but there are difficulties in its practical implementation. Organizational, registration of tracks of all kinds of dangerous invasions, is carried out from stationary, mobile and aircraft (quadrocopters, drones, unmanned aerial vehicles) astronomical observatories of terrestrial aerospace monitoring services. Registered by us at daytime and twilight traces can be seen from a few minutes, sometimes up to two hours [1, 2, 4, 6-10].

DUOX enzyme activity promotes AKT signalling in prostate cancer cells.

Science.gov (United States)

Pettigrew, Christopher A; Clerkin, John S; Cotter, Thomas G

2012-12-01

Reactive oxygen species (ROS) and oxidative stress are related to tumour progression, and high levels of ROS have been observed in prostate tumours compared to normal prostate. ROS can positively influence AKT signalling and thereby promote cell survival. The aim of this project was to establish whether the ROS generated in prostate cancer cells positively regulate AKT signalling and enable resistance to apoptotic stimuli. In PC3 cells, dual oxidase (DUOX) enzymes actively generate ROS, which inactivate phosphatases, thereby maintaining AKT phosphorylation. Inhibition of DUOX by diphenylene iodium (DPI), intracellular calcium chelation and small-interfering RNA (siRNA) resulted in lower ROS levels, lower AKT and glycogen synthase kinase 3β (GSK3β) phosphorylation, as well as reduced cell viability and increased susceptibility to apoptosis stimulating fragment (FAS) induced apoptosis. This report shows that ROS levels in PC3 cells are constitutively maintained by DUOX enzymes, and these ROS positively regulate AKT signalling through inactivating phosphatases, leading to increased resistance to apoptosis.

Peafowl antipredator calls encode information about signalers.

Science.gov (United States)

Yorzinski, Jessica L

2014-02-01

Animals emit vocalizations that convey information about external events. Many of these vocalizations, including those emitted in response to predators, also encode information about the individual that produced the call. The relationship between acoustic features of antipredator calls and information relating to signalers (including sex, identity, body size, and social rank) were examined in peafowl (Pavo cristatus). The "bu-girk" antipredator calls of male and female peafowl were recorded and 20 acoustic parameters were automatically extracted from each call. Both the bu and girk elements of the antipredator call were individually distinctive and calls were classified to the correct signaler with over 90% and 70% accuracy in females and males, respectively. Females produced calls with a higher fundamental frequency (F0) than males. In both females and males, body size was negatively correlated with F0. In addition, peahen rank was related to the duration, end mean frequency, and start harmonicity of the bu element. Peafowl antipredator calls contain detailed information about the signaler and can potentially be used by receivers to respond to dangerous situations.

FACTORS RELATED TO KNOWLEDGE ON NEWBORN DANGER SIGNS AMONG THE RECENTLY DELIVERED WOMEN IN SUB-DISTRICT HOSPITALS OF BANGLADESH

Directory of Open Access Journals (Sweden)

Sojib Bin Zaman

2017-06-01

Full Text Available Background: Bangladesh continues to be one of the top ten countries with the highest burden of neonatal mortality. While, most of the neonatal deaths are preventable; health system delays, delayed identification of newborn danger signs, late diagnosis and initiation of treatment are claimed to be the main challenges. Objective: 1 to determine the level of knowledge among the recently delivered women (RDW about newborn danger signs and 2 to distinguish the factors associated with ability of identifying the danger signs. Methods: A facility based cross-sectional study was conducted in three sub-district hospitals of Bangladesh among 135 RDW between 1 January 2015 and 30 April 2015. Seven key danger signs were identified, and responses were categorized accordingly. Bivariable logistic regression was conducted to determine the likelihood of the association of factors with danger signs identification. Results: About 51% of RDW could identify one key danger sign. Knowledge on “fever’’ was the most commonly known danger sign (65%. Middle age (OR 1.67, 95% CI: 1.09 - 2.18, high education (OR 2.37, 95% CI: 1.46 - 2.77, increased parity (OR 1.91, 95% CI: 1.17 - 2.89, and previous hospital delivery (OR 1.79, 95% CI: 1.14 - 2.68 were found associated with the knowl¬edge of the danger signs. Conclusion: The findings indicate the immediate need to enhance health education among the RDW about newborn danger signs before their hospital discharge. Community based health education programs can be a cost effective intervention to increase awareness and early recognition of neonatal danger signs.

Awareness of eSafety and Potential Online Dangers among Children and Teenagers

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Gila Cohen Zilka

2017-09-01

Background\tThe study examined eSafety among children and teenagers from their own perspectives, through evaluations of their awareness level of eSafety and of potential online dangers. Methodology: This is a mixed-method study with both quantitative and qualitative elements. The study includes questionnaires and interviews. A total of 345 participants from Israel completed questionnaires; 90 children and teenagers were interviewed from among the participants. Contribution: The study examined the awareness of children and youths of safe online surfing. It also examined the degree of exposure of children and youths to positive and negative aspects of the Internet. This study illustrates the dual potential of Internet use within the context of eSafety, as seen through the eyes of children and teenagers. Characteristics of use of the Internet are liable to increase the danger to and the bullying of youths and by youths in the digital domain. It also demonstrates the promises of using the Internet for productive learning and leisure activities. Findings: Findings show that the children and teenagers who participated in the study reported a medium-high level of awareness. Issues that participants were concerned about included avoiding contact with strangers and cyberbullying, not necessarily by strangers, but also by friends. Recommendations for Practitioners\t: It is important to examine how children perceive online events for the purpose of examining their statements regarding eSafety and the way they view problematic or dangerous online events, as well as how they believe they can cope with them. Recommendation for Researchers: The study recommends incorporating in future studies individual case studies and allowing participants to express how they perceive complex online situations. Impact on Society: This study illustrates the dual potential, positive and negative aspects, of Internet use within the context of eSafety, as seen through the eyes of children and

Obstetric danger signs and factors affecting health seeking behaviour among the Kassena-Nankani of Northern Ghana: a qualitative study.

Science.gov (United States)

Aborigo, Raymond A; Moyer, Cheryl A; Gupta, Mira; Adongo, Philip B; Williams, John; Hodgson, Abraham; Allote, Pascale; Engmann, Cyril M

2014-09-01

Improving community members' knowledge of obstetric danger signs is one strategy for increasing the use of skilled care during pregnancy and the puerperium. This study explored knowledge of obstetric danger signs among a range of community members, examined the sources of their information, and the perceived factors that affect health seeking behaviour in rural northern Ghana. We conducted 72 in-depth interviews and 18 focus groups with community members. All interactions were audio taped, transcribed verbatim and analysed using NVivo 9.0. Community members demonstrated knowledge of a wide range of obstetric danger signs, including excessive bleeding, stomach aches, waist pains, vomiting and fever. Pregnant women learn about danger signs from a range of providers, and regular contact with formal providers typically coincided with increased knowledge of danger signs. Traditional remedies for problems in obstetrics are plentiful and cultural beliefs often restrict the use of allopathic medicine. Increasing knowledge of obstetric danger signs is necessary but not sufficient to overcome cultural preferences for traditional treatments for pregnancy danger signs.

Decision of the National Board of Navigation on the Carriage of Dangerous Goods in Ships

International Nuclear Information System (INIS)

1980-01-01

This is an unofficial English translation of a decision, which was made in accordance with Section 12 of Decree No. 357 of 16th May 1980 on the Carriage of Dangerous Goods in Ships. It adopts by reference the IMO/IMDG Code with the packaging Annex and Amendments 1 - 21. Where the National Board of Navigation has not provided otherwise, the Code shall be applied to vessels carrying dangerous goods, to the classification, packing, marketing and handling of dangerous goods and the stowage of such goods on board, and to documents related to carriage of dangerous goods. The decision applies to vessels engaged in traffic in Finnish territorial waters and to all Finnish vessels, even when operating outside Finnish territorial waters. The decision designates the Finnish Centre for Radiation and Nuclear Safety as the competent authority where approval certificates for transport, packages or containers of radioactive materials are required. (NEA) [fr

Nutrient tasting and signaling mechanisms in the gut V. Mechanisms of immunologic sensation of intestinal contents.

LENUS (Irish Health Repository)

Shanahan, F

2012-02-03

Immune perception of intestinal contents reflects a functional dualism with systemic hyporesponsiveness to dietary antigens and resident microflora (oral tolerance) and active immune responses to mucosal pathogens. This facilitates optimal absorption of dietary nutrients while conserving immunologic resources for episodic pathogenic challenge. Discrimination between dangerous and harmless antigens within the enteric lumen requires continual sampling of the microenvironment by multiple potential pathways, innate and adaptive recognition mechanisms, bidirectional lymphoepithelial signaling, and rigorous control of effector responses. Errors in these processes disrupt mucosal homeostasis and are associated with food hypersensitivity and mucosal inflammation. Mechanisms of mucosal immune perception and handling of dietary proteins and other antigens have several practical and theoretical implications including vaccine design, therapy of systemic autoimmunity, and alteration of enteric flora with probiotics.

Education and the Dangerous Memories of Historical Trauma: Narratives of Pain, Narratives of Hope

Science.gov (United States)

Zembylas, Michalinos; Bekerman, Zvi

2008-01-01

The purpose of this article is to explore the meanings and implications of dangerous memories in two different sites of past traumatic memories: one in Israel and the other in Cyprus. Dangerous memories are defined as those memories that are disruptive to the status quo, that is, the hegemonic culture of strengthening and perpetuating existing…

Macrophages activate iNOS signaling in adventitial fibroblasts and contribute to adventitia fibrosis.

Science.gov (United States)

Zhang, Guannan; Li, Xiaodong; Sheng, Chengyu; Chen, Xiaohui; Chen, Yu; Zhu, Dingliang; Gao, Pingjin

2016-12-30

A large amount of NO is generated through the inducible nitric oxide synthase (iNOS) pathway from the vascular adventitia in various vascular diseases. However, it is currently not fully understood how the iNOS signaling pathway is activated. In the present study, this question was addressed in the context of adventitial cellular interactions. A rat model of acute hypertension in the contralateral carotid arteries was established through transverse aortic constriction (TAC) surgery. In this model, activated macrophages were found surrounded by a large quantity of iNOS-expressing adventitial fibroblasts (AFs), suggesting a possible causal relationship between macrophages and iNOS activation of the neighboring AFs. In an in vitro model, a macrophage-like cell line RAW 264.7 was first activated by LPS treatment. The supernatant was then harvested and applied to treat primary rat AFs. iNOS in AFs was activated robustly by the supernatant treatment but not by LPS itself. Treating AFs with interleukin-1β (IL-1β) also activated iNOS signaling, suggesting that the IL-1β pathway might be a possible mediator. As a consequence of the iNOS activation, total protein nitration and S-nitrosylation significantly increased in those AFs. Additionally, increased deposition of type I and type III collagens was observed in both in vitro and in vivo models. The collagen deposition was partially restored by an iNOS inhibitor, 1400 W. These findings highlight the importance of iNOS signaling during vascular inflammation, and advance our understanding of its activation through a cellular interaction perspective. Copyright © 2016 Elsevier Inc. All rights reserved.

Study of Car Acceleration and Deceleration Characteristics at Dangerous Route FT050

Science.gov (United States)

Omar, N.; Prasetijo, J.; Daniel, B. D.; Abdullah, M. A. E.; Ismail, I.

2018-04-01

Individual vehicle acceleration and deceleration are important to generate vehicles speed profile. This study covered acceleration and deceleration characteristics of passenger car in Federal Route FT050 Jalan Batu Pahat-Ayer Hitam that was the top ranking dangerous road. Global Positioning System was used to record 10 cars speed to develop speed profile with clustering zone. At the acceleration manoeuver, the acceleration rate becomes lower as the drivers get near to desired speed. While, at deceleration manoeuver, vehicles with high speed needs more time to stop compare to low speed vehicle. This is because, the drivers need to accelerate more from zero speed to achieve desired speed and drivers need more distance and time to stop their vehicles. However, it was found out that 30% to 50% are driving in dangerous condition that was proven in clustering acceleration and deceleration speed profile. As conclusion, this excessive drivers are the factor that creating high risk in rear-end collision that inline FT050 as dangerous road in Malaysia

Acetic acid activates the AMP-activated protein kinase signaling pathway to regulate lipid metabolism in bovine hepatocytes.

Directory of Open Access Journals (Sweden)

Xinwei Li

Full Text Available The effect of acetic acid on hepatic lipid metabolism in ruminants differs significantly from that in monogastric animals. Therefore, the aim of this study was to investigate the regulation mechanism of acetic acid on the hepatic lipid metabolism in dairy cows. The AMP-activated protein kinase (AMPK signaling pathway plays a key role in regulating hepatic lipid metabolism. In vitro, bovine hepatocytes were cultured and treated with different concentrations of sodium acetate (neutralized acetic acid and BML-275 (an AMPKα inhibitor. Acetic acid consumed a large amount of ATP, resulting in an increase in AMPKα phosphorylation. The increase in AMPKα phosphorylation increased the expression and transcriptional activity of peroxisome proliferator-activated receptor α, which upregulated the expression of lipid oxidation genes, thereby increasing lipid oxidation in bovine hepatocytes. Furthermore, elevated AMPKα phosphorylation reduced the expression and transcriptional activity of the sterol regulatory element-binding protein 1c and the carbohydrate responsive element-binding protein, which reduced the expression of lipogenic genes, thereby decreasing lipid biosynthesis in bovine hepatocytes. In addition, activated AMPKα inhibited the activity of acetyl-CoA carboxylase. Consequently, the triglyceride content in the acetate-treated hepatocytes was significantly decreased. These results indicate that acetic acid activates the AMPKα signaling pathway to increase lipid oxidation and decrease lipid synthesis in bovine hepatocytes, thereby reducing liver fat accumulation in dairy cows.

Silybin-mediated inhibition of Notch signaling exerts antitumor activity in human hepatocellular carcinoma cells.

Directory of Open Access Journals (Sweden)

Song Zhang

Full Text Available Hepatocellular carcinoma (HCC is a global health burden that is associated with limited treatment options and poor patient prognoses. Silybin (SIL, an antioxidant derived from the milk thistle plant (Silybum marianum, has been reported to exert hepatoprotective and antitumorigenic effects both in vitro and in vivo. While SIL has been shown to have potent antitumor activity against various types of cancer, including HCC, the molecular mechanisms underlying the effects of SIL remain largely unknown. The Notch signaling pathway plays crucial roles in tumorigenesis and immune development. In the present study, we assessed the antitumor activity of SIL in human HCC HepG2 cells in vitro and in vivo and explored the roles of the Notch pathway and of the apoptosis-related signaling pathway on the activity of SIL. SIL treatment resulted in a dose- and time-dependent inhibition of HCC cell viability. Additionally, SIL exhibited strong antitumor activity, as evidenced not only by reductions in tumor cell adhesion, migration, intracellular glutathione (GSH levels and total antioxidant capability (T-AOC but also by increases in the apoptotic index, caspase3 activity, and reactive oxygen species (ROS. Furthermore, SIL treatment decreased the expression of the Notch1 intracellular domain (NICD, RBP-Jκ, and Hes1 proteins, upregulated the apoptosis pathway-related protein Bax, and downregulated Bcl2, survivin, and cyclin D1. Notch1 siRNA (in vitro or DAPT (a known Notch1 inhibitor, in vivo further enhanced the antitumor activity of SIL, and recombinant Jagged1 protein (a known Notch ligand in vitro attenuated the antitumor activity of SIL. Taken together, these data indicate that SIL is a potent inhibitor of HCC cell growth that targets the Notch signaling pathway and suggest that the inhibition of Notch signaling may be a novel therapeutic intervention for HCC.

Hyaluronan activates Hyal-2/WWOX/Smad4 signaling and causes bubbling cell death when the signaling complex is overexpressed

Science.gov (United States)

Hsu, Li-Jin; Hong, Qunying; Chen, Shur-Tzu; Kuo, Hsiang-Lin; Schultz, Lori; Heath, John; Lin, Sing-Ru; Lee, Ming-Hui; Li, Dong-Zhang; Li, Zih-Ling; Cheng, Hui-Ching; Armand, Gerard; Chang, Nan-Shan

2017-01-01

Malignant cancer cells frequently secrete significant amounts of transforming growth factor beta (TGF-β), hyaluronan (HA) and hyaluronidases to facilitate metastasizing to target organs. In a non-canonical signaling, TGF-β binds membrane hyaluronidase Hyal-2 for recruiting tumor suppressors WWOX and Smad4, and the resulting Hyal-2/WWOX/Smad4 complex is accumulated in the nucleus to enhance SMAD-promoter dependent transcriptional activity. Yeast two-hybrid analysis showed that WWOX acts as a bridge to bind both Hyal-2 and Smad4. When WWOX-expressing cells were stimulated with high molecular weight HA, an increased formation of endogenous Hyal-2/WWOX/Smad4 complex occurred rapidly, followed by relocating to the nuclei in 20-40 min. In WWOX-deficient cells, HA failed to induce Smad2/3/4 relocation to the nucleus. To prove the signaling event, we designed a real time tri-molecular FRET analysis and revealed that HA induces the signaling pathway from ectopic Smad4 to WWOX and finally to p53, as well as from Smad4 to Hyal-2 and then to WWOX. An increased binding of the Smad4/Hyal-2/WWOX complex occurs with time in the nucleus that leads to bubbling cell death. In contrast, HA increases the binding of Smad4/WWOX/p53, which causes membrane blebbing but without cell death. In traumatic brain injury-induced neuronal death, the Hyal-2/WWOX complex was accumulated in the apoptotic nuclei of neurons in the rat brains in 24 hr post injury, as determined by immunoelectron microscopy. Together, HA activates the Hyal-2/WWOX/Smad4 signaling and causes bubbling cell death when the signaling complex is overexpressed. PMID:27845895

Royal Decree 1749/1984 of 1 August approving the national regulations on the safe transport of dangerous goods by air together with technical instructions for the safe transport of dangerous goods by air

International Nuclear Information System (INIS)

1984-01-01

This Royal Decree approves the national Regulations on the safe transport of dangerous goods by air. The Regulations as well as the attached detailed technical instructions are based on the 1981 revised text of the Annex concerning dangerous goods of the Chicago Convention on International Civil Aviation. It also covers radioactive materials. (NEA) [fr

Social Contradictions and Change in Okri's Dangerous Love ...

African Journals Online (AJOL)

Ben Okri is one of Africa's most experimental contemporary novelists in the Magical realist tradition through which he has carved a nitch for himself. In this paper we critically interrogate his utilization of the magic realist form in Dangerous Love to examine the theme of contradiction and love. Through a Marxist dialectic ...

Signal formation and active edge studies of 3D silicon detector technology

CERN Document Server

Kok, Angela

3D detectors and devices with an ‘active edge’ were fabricated at the Stanford Nanofabrication Facility. Characteristics such as time response and edge sensitivity were studied. The induced signals from a 3D detector were studied using a fast, low-noise transimpedance amplifier. The rise time of the output signal obtained for a minimum ionising particle was faster than 4 ns at room temperature and 2 ns at 130K. This is in agreement with earlier calculations of 3D detectors that predicted the charge collection time to be between one to two ns. The first understanding of signal formation in a 3D detector was achieved by comparing measurements with a full system simulation. The differences in collection behaviour between electrons and holes were also understood and verified by measurement. Edge sensitivity was measured at the CERN SPS, using a high energy muon beam and a silicon telescope. The detector was measured to be efficient up to less than 4 μm from its physical edge. This confirmed that active edge ...

The 1978 National Fire-Danger Rating System: technical documentation

Science.gov (United States)

Larry S. Bradshaw; John E. Deeming; Robert E. Burgan; Jack D. Cohen

1984-01-01

The National Fire-Danger Rating System (NFDRS), implemented in 1972, has been revised and reissued as the 1978 NFDRS. This report describes the full developmental history of the NFDRS, including purpose, technical foundation, and structure. Includes an extensive bibliography and appendixes.

Activation of stress signaling molecules in bat brain during arousal from hibernation.

Science.gov (United States)

Lee, Moonyong; Choi, Inho; Park, Kyoungsook

2002-08-01

Induction of glucose-regulated proteins (GRPs) is a ubiquitous intracellular response to stresses such as hypoxia, glucose starvation and acidosis. The induction of GRPs offers some protection against these stresses in vitro, but the specific role of GRPs in vivo remains unclear. Hibernating bats present a good in vivo model to address this question. The bats must overcome local high oxygen demand in tissue by severe metabolic stress during arousal thermogenesis. We used brain tissue of a temperate bat Rhinolopus ferrumequinum to investigate GRP induction by high metabolic oxygen demand and to identify associated signaling molecules. We found that during 30 min of arousal, oxygen consumption increased from nearly zero to 11.9/kg/h, which was about 8.7-fold higher than its active resting metabolic rate. During this time, body temperature rose from 7 degrees C to 35 degrees C, and levels of TNF-alpha and lactate in brain tissue increased 2-2.5-fold, indicating a high risk of oxygen shortage. Concomitantly, levels of GRP75, GRP78 and GRP94 increased 1.5-1.7-fold. At the same time, c-Jun N-terminal protein kinase (JNK) activity increased 6.4-fold, and extracellular signal-regulated protein kinase (ERK) activity decreased to a similar degree (6.1-fold). p38 MAPK activity was very low and remained unchanged during arousal. In addition, survival signaling molecules protein kinase B (Akt) and protein kinase C (PKC) were activated 3- and 5-fold, respectively, during arousal. Taken together, our results showed that bat brain undergoes high oxygen demand during arousal from hibernation. Up-regulation of GRP proteins and activation of JNK, PKCgamma and Akt may be critical for neuroprotection and the survival of bats during the repeated process.

An apodized Kepler periodogram for separating planetary and stellar activity signals

Science.gov (United States)

Gregory, Philip C.

2016-01-01

A new apodized Keplerian (AK) model is proposed for the analysis of precision radial velocity (RV) data to model both planetary and stellar activity (SA) induced RV signals. A symmetrical Gaussian apodization function with unknown width and centre can distinguish planetary signals from SA signals on the basis of the span of the apodization window. The general model for m AK signals includes a linear regression term between RV and the SA diagnostic log (R′hk), as well as an extra Gaussian noise term with unknown standard deviation. The model parameters are explored using a Bayesian fusion Markov chain Monte Carlo code. A differential version of the generalized Lomb–Scargle periodogram that employs a control diagnostic provides an additional way of distinguishing SA signals and helps guide the choice of new periods. Results are reported for a recent international RV blind challenge which included multiple state-of-the-art simulated data sets supported by a variety of SA diagnostics. In the current implementation, the AK method achieved a reduction in SA noise by a factor of approximately 6. Final parameter estimates for the planetary candidates are derived from fits that include AK signals to model the SA components and simple Keplerians to model the planetary candidates. Preliminary results are also reported for AK models augmented by a moving average component that allows for correlations in the residuals. PMID:27346979

A MATLAB-based graphical user interface for the identification of muscular activations from surface electromyography signals.

Science.gov (United States)

Mengarelli, Alessandro; Cardarelli, Stefano; Verdini, Federica; Burattini, Laura; Fioretti, Sandro; Di Nardo, Francesco

2016-08-01

In this paper a graphical user interface (GUI) built in MATLAB® environment is presented. This interactive tool has been developed for the analysis of superficial electromyography (sEMG) signals and in particular for the assessment of the muscle activation time intervals. After the signal import, the tool performs a first analysis in a totally user independent way, providing a reliable computation of the muscular activation sequences. Furthermore, the user has the opportunity to modify each parameter of the on/off identification algorithm implemented in the presented tool. The presence of an user-friendly GUI allows the immediate evaluation of the effects that the modification of every single parameter has on the activation intervals recognition, through the real-time updating and visualization of the muscular activation/deactivation sequences. The possibility to accept the initial signal analysis or to modify the on/off identification with respect to each considered signal, with a real-time visual feedback, makes this GUI-based tool a valuable instrument in clinical, research applications and also in an educational perspective.

Head direction cell activity in mice: robust directional signal depends on intact otolith organs

Science.gov (United States)

Yoder, Ryan M.; Taube, Jeffrey S.

2009-01-01

The head direction (HD) cell signal is a representation of an animal's perceived directional heading with respect to its environment. This signal appears to originate in the vestibular system, which includes the semicircular canals and otolith organs. Preliminary studies indicate the semicircular canals provide a necessary component of the HD signal, but involvement of otolithic information in the HD signal has not been tested. The present study was designed to determine the otolithic contribution to the HD signal, as well as to compare HD cell activity of mice to that of rats. HD cell activity in the anterodorsal thalamus was assessed in wild-type C57BL/6J and otoconia-deficient tilted mice during locomotion within a cylinder containing a prominent visual landmark. HD cell firing properties in C57BL/6J mice were generally similar to those in rats. However, in C57BL/6J mice, landmark rotation failed to demonstrate dominant control of the HD signal in 36% of the sessions. In darkness, directional firing became unstable during 42% of the sessions, but landmark control was not associated with HD signal stability in darkness. HD cells were identified in tilted mice, but directional firing properties were not as robust as those of C57BL/6J mice. Most HD cells in tilted mice were controlled by landmark rotation, but showed substantial signal degradation across trials. These results support current models that suggest otolithic information is involved in the perception of directional heading. Furthermore, compared to rats, the HD signal in mice appears to be less reliably anchored to prominent environmental cues. PMID:19176815

Fire danger rating over Mediterranean Europe based on fire radiative power derived from Meteosat

Science.gov (United States)

Pinto, Miguel M.; DaCamara, Carlos C.; Trigo, Isabel F.; Trigo, Ricardo M.; Feridun Turkman, K.

2018-02-01

We present a procedure that allows the operational generation of daily forecasts of fire danger over Mediterranean Europe. The procedure combines historical information about radiative energy released by fire events with daily meteorological forecasts, as provided by the Satellite Application Facility for Land Surface Analysis (LSA SAF) and the European Centre for Medium-Range Weather Forecasts (ECMWF). Fire danger is estimated based on daily probabilities of exceedance of daily energy released by fires occurring at the pixel level. Daily probability considers meteorological factors by means of the Canadian Fire Weather Index (FWI) and is estimated using a daily model based on a generalized Pareto distribution. Five classes of fire danger are then associated with daily probability estimated by the daily model. The model is calibrated using 13 years of data (2004-2016) and validated against the period of January-September 2017. Results obtained show that about 72 % of events releasing daily energy above 10 000 GJ belong to the extreme class of fire danger, a considerably high fraction that is more than 1.5 times the values obtained when using the currently operational Fire Danger Forecast module of the European Forest Fire Information System (EFFIS) or the Fire Risk Map (FRM) product disseminated by the LSA SAF. Besides assisting in wildfire management, the procedure is expected to help in decision making on prescribed burning within the framework of agricultural and forest management practices.

Fire danger rating over Mediterranean Europe based on fire radiative power derived from Meteosat

Directory of Open Access Journals (Sweden)

M. M. Pinto

2018-02-01

Full Text Available We present a procedure that allows the operational generation of daily forecasts of fire danger over Mediterranean Europe. The procedure combines historical information about radiative energy released by fire events with daily meteorological forecasts, as provided by the Satellite Application Facility for Land Surface Analysis (LSA SAF and the European Centre for Medium-Range Weather Forecasts (ECMWF. Fire danger is estimated based on daily probabilities of exceedance of daily energy released by fires occurring at the pixel level. Daily probability considers meteorological factors by means of the Canadian Fire Weather Index (FWI and is estimated using a daily model based on a generalized Pareto distribution. Five classes of fire danger are then associated with daily probability estimated by the daily model. The model is calibrated using 13 years of data (2004–2016 and validated against the period of January–September 2017. Results obtained show that about 72 % of events releasing daily energy above 10 000 GJ belong to the extreme class of fire danger, a considerably high fraction that is more than 1.5 times the values obtained when using the currently operational Fire Danger Forecast module of the European Forest Fire Information System (EFFIS or the Fire Risk Map (FRM product disseminated by the LSA SAF. Besides assisting in wildfire management, the procedure is expected to help in decision making on prescribed burning within the framework of agricultural and forest management practices.

The shaking signal of the honey bee informs workers to prepare for greater activity

OpenAIRE

Seeley, Thomas D.; Weidenmüller, Anja; Kühnholz, Susanne

2010-01-01

One of the most conspicuous activities o f worker bees inside a hive is the shaking of other wc~rliersT. his shaking has long been suspected to be a communication behavior, but its information content and function have until recently remained mysterious. Prior studies of the colony-level patterns of the production of ihc shaking signal supgest strongly that this signal semes to arouse workers to greater activity, such as at times of good foraging. Data from our obsenrauons of mdividual bees h...

Mid-term fire danger index based on satellite imagery and ancillary geographic data

Science.gov (United States)

Stefanidou, A.; Dragozi, E.; Tompoulidou, M.; Stepanidou, L.; Grigoriadis, D.; Katagis, T.; Stavrakoudis, D.; Gitas, I.

2017-09-01

Fire danger forecast constitutes one of the most important components of integrated fire management since it provides crucial information for efficient pre-fire planning, alertness and timely response to a possible fire event. The aim of this work is to develop an index that has the capability of predicting accurately fire danger on a mid-term basis. The methodology that is currently under development is based on an innovative approach that employs dry fuel spatial connectivity as well as biophysical and topological variables for the reliable prediction of fire danger. More specifically, the estimation of the dry fuel connectivity is based on a previously proposed automated procedure implemented in R software that uses Moderate Resolution Imaging Spectrometer (MODIS) time series data. Dry fuel connectivity estimates are then combined with other ancillary data such as fuel type and proximity to roads in order to result in the generation of the proposed mid-term fire danger index. The innovation of the proposed index—which will be evaluated by comparison to historical fire data—lies in the fact that its calculation is almost solely affected by the availability of satellite data. Finally, it should be noted that the index is developed within the framework of the National Observatory of Forest Fires (NOFFi) project.

Audit on the Use of Dangerous Abbreviations, Symbols, and Dose Designations in Paper Compared to Electronic Medication Orders: A Multicenter Study.

Science.gov (United States)

Cheung, Stephanie; Hoi, Sannifer; Fernandes, Olavo; Huh, Jin; Kynicos, Sara; Murphy, Laura; Lowe, Donna

2018-04-01

Dangerous abbreviations on the Institute for Safe Medication Practices Canada's "Do Not Use" list have resulted in medication errors leading to harm. Data comparing rates of use of dangerous abbreviations in paper and electronic medication orders are limited. To compare rates of use of dangerous abbreviations from the "Do Not Use" list, in paper and electronic medication orders. Secondary objectives include determining the proportion of patients at risk for medication errors due to dangerous abbreviations and the most commonly used dangerous abbreviations. One-day cross-sectional audits of medication orders were conducted at a 6-site hospital network in Toronto, Canada, between December 2013 and January 2014. Proportions of paper and electronic medication orders containing dangerous abbreviation(s) were compared using a χ 2 test. The proportion of patients with at least 1 medication order containing dangerous abbreviation(s) and the top 5 dangerous abbreviations used were described. Overall, 255 patient charts were reviewed. The proportions of paper and electronic medication orders containing dangerous abbreviation(s) were 172/714 (24.1%) and 9/2207 (0.4%), respectively ( P < 0.001). Almost one-third of patients had medication order(s) containing dangerous abbreviation(s). The proportions of patients with at least 1 medication order during the audit period containing dangerous abbreviation(s) for patients with paper only, electronic only, or a hybrid of paper and electronic medication orders were 50.5%, 5%, and 47.2%, respectively. Those most commonly used were "D/C", drug name abbreviations, "OD," "cc," and "U." Electronic medication orders have significantly lower rates of dangerous abbreviation use compared to paper medication orders.

Oridonin stabilizes retinoic acid receptor alpha through ROS-activated NF-κB signaling.

Science.gov (United States)

Cao, Yang; Wei, Wei; Zhang, Nan; Yu, Qing; Xu, Wen-Bin; Yu, Wen-Jun; Chen, Guo-Qiang; Wu, Ying-Li; Yan, Hua

2015-04-10

Retinoic acid receptor alpha (RARα) plays an essential role in the regulation of many biological processes, such as hematopoietic cell differentiation, while abnormal RARα function contributes to the pathogenesis of certain diseases including cancers, especially acute promyelocytic leukemia (APL). Recently, oridonin, a natural diterpenoid isolated from Rabdosia rubescens, was demonstrated to regulate RARα by increasing its protein level. However, the underlying molecular mechanism for this action has not been fully elucidated. In the APL cell line, NB4, the effect of oridonin on RARα protein was analyzed by western blot and real-time quantitative RT-PCR analyses. Flow cytometry was performed to detect intracellular levels of reactive oxygen species (ROS). The association between nuclear factor-kappa B (NF-κB) signaling and the effect of oridonin was assessed using specific inhibitors, shRNA gene knockdown, and immunofluorescence assays. In addition, primary leukemia cells were treated with oridonin and analyzed by western blot in this study. RARα possesses transcriptional activity in the presence of its ligand, all-trans retinoic acid (ATRA). Oridonin remarkably stabilized the RARα protein, which retained transcriptional activity. Oridonin also moderately increased intracellular ROS levels, while pretreatment with the ROS scavenger, N-acetyl-l-cysteine (NAC), dramatically abrogated RARα stabilization by oridonin. More intriguingly, direct exposure to low concentrations of H2O2 also increased RARα protein but not mRNA levels, suggesting a role for ROS in oridonin stabilization of RARα protein. Further investigations showed that NAC antagonized oridonin-induced activation of NF-κB signaling, while the NF-κB signaling inhibitor, Bay 11-7082, effectively blocked the oridonin increase in RARα protein levels. In line with this, over-expression of IκΒα (A32/36), a super-repressor form of IκΒα, or NF-κB-p65 knockdown inhibited oridonin or H2O2-induced

New Insights into Glomerular Parietal Epithelial Cell Activation and Its Signaling Pathways in Glomerular Diseases

Directory of Open Access Journals (Sweden)

Hua Su

2015-01-01

Full Text Available The glomerular parietal epithelial cells (PECs have aroused an increasing attention recently. The proliferation of PECs is the main feature of crescentic glomerulonephritis; besides that, in the past decade, PEC activation has been identified in several types of noninflammatory glomerulonephropathies, such as focal segmental glomerulosclerosis, diabetic glomerulopathy, and membranous nephropathy. The pathogenesis of PEC activation is poorly understood; however, a few studies delicately elucidate the potential mechanisms and signaling pathways implicated in these processes. In this review we will focus on the latest observations and concepts about PEC activation in glomerular diseases and the newest identified signaling pathways in PEC activation.

Dangers of social networking sites- the propagation of malware

CSIR Research Space (South Africa)

Labuschagne, WA

2013-07-01

Full Text Available The paper will illustrate the dangers of social networking malware through examples. In addition, the paper will discuss propagation techniques used in social networking malware. The aim of the paper is to create user awareness to minimise the risk...

Avoiding Dangerous Anthropogenic Interference with the Climate System

Energy Technology Data Exchange (ETDEWEB)

Keller, K. [Department of Geosciences, Penn State, PA (United States); Hall, M. [Brookings Institution, Washington, DC (United States); Kim, Seung-Rae [Woodrow Wilson School of Public and International Affairs, Princeton University, Princeton, NJ (United States); Bradford, D.F. [Department of Economics, Princeton University, Princeton, NJ (United States); Oppenheimer, M. [Woodrow Wilson School and Department of Geosciences, Princeton University, Robertson Hall 448, Princeton, NJ, 08544 (United States)

2005-12-01

The UN Framework Convention on Climate Change calls for the avoidance of 'dangerous anthropogenic interference with the climate system'. Among the many plausible choices, dangerous interference with the climate system may be interpreted as anthropogenic radiative forcing causing distinct and widespread climate change impacts such as a widespread demise of coral reefs or a disintegration of the West Antarctic ice sheet. The geological record and numerical models suggest that limiting global warming below critical temperature thresholds significantly reduces the likelihood of these eventualities. Here we analyze economically optimal policies that may ensure this risk-reduction. Reducing the risk of a widespread coral reef demise implies drastic reductions in greenhouse gas emissions within decades. Virtually unchecked greenhouse gas emissions to date (combined with the inertia of the coupled natural and human systems) may have already committed future societies to a widespread demise of coral reefs. Policies to reduce the risk of a West Antarctic ice sheet disintegration allow for a smoother decarbonization of the economy within a century and may well increase consumption in the long run.

Dangerous relation: chivalrousness and sexism through a look at the novel of Laclos

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Juliana Carneiro da Silva

2012-05-01

Full Text Available Product of a scientific initiation research, this article part of un hermeneutic interpretation of the novel by Choderlos de Laclos (Dangerous Relations, 1971 and his filmic adaptation (Dangerous Liaisons, Stephen Frears, 1988 in search of launching a new look at the male figures of gentleman and sexist, understand them as movements that are approaching, cohabit, interpenetrate and infl uence, confi guring the chivalrousness a form of change to stay for sexism.

By-law from December 5, 1996 relative to the road transport of dangerous goods (called ''ADR by-law''). (Dangerous materials no. 1)

International Nuclear Information System (INIS)

Mesnil, H. du

1996-01-01

The aim of this by-law from the French ministry of equipment, lodging, transports and tourism is to define the specific rules that must be applied in France to the national or international road transport of dangerous freight (radioactive materials, explosive materials, under pressure compressed, liquefied or dissolved gases, flammable liquids and solids, spontaneously flammable materials, combustive agents, organic peroxides, noxious, infectious and corrosive materials etc..). The classification of dangerous materials and the freight that cannot be transported by road is listed in two appendixes [700 p.] at the end of the document. This by-law gives the rules concerning: the building, testing, agreement, labelling, periodical controls and conditions for use of packing materials, drums, containers, tanks and vehicles; the equipments, the loading and unloading, the running and parking of vehicles; the training of personnel and the organization of companies; the documents for control or safety assistance. Special rules concerning the transportation of gamma radiography apparatuses are given. (J.S.)

Activation of cAMP-dependent signaling induces oxidative modification of the cardiac Na+-K+ pump and inhibits its activity.

Science.gov (United States)

White, Caroline N; Liu, Chia-Chi; Garcia, Alvaro; Hamilton, Elisha J; Chia, Karin K M; Figtree, Gemma A; Rasmussen, Helge H

2010-04-30

Cellular signaling can inhibit the membrane Na(+)-K(+) pump via protein kinase C (PKC)-dependent activation of NADPH oxidase and a downstream oxidative modification, glutathionylation, of the beta(1) subunit of the pump alpha/beta heterodimer. It is firmly established that cAMP-dependent signaling also regulates the pump, and we have now examined the hypothesis that such regulation can be mediated by glutathionylation. Exposure of rabbit cardiac myocytes to the adenylyl cyclase activator forskolin increased the co-immunoprecipitation of NADPH oxidase subunits p47(phox) and p22(phox), required for its activation, and increased superoxide-sensitive fluorescence. Forskolin also increased glutathionylation of the Na(+)-K(+) pump beta(1) subunit and decreased its co-immunoprecipitation with the alpha(1) subunit, findings similar to those already established for PKC-dependent signaling. The decrease in co-immunoprecipitation indicates a decrease in the alpha(1)/beta(1) subunit interaction known to be critical for pump function. In agreement with this, forskolin decreased ouabain-sensitive electrogenic Na(+)-K(+) pump current (arising from the 3:2 Na(+):K(+) exchange ratio) of voltage-clamped, internally perfused myocytes. The decrease was abolished by the inclusion of superoxide dismutase, the inhibitory peptide for the epsilon-isoform of PKC or inhibitory peptide for NADPH oxidase in patch pipette solutions that perfuse the intracellular compartment. Pump inhibition was also abolished by inhibitors of protein kinase A and phospholipase C. We conclude that cAMP- and PKC-dependent inhibition of the cardiac Na(+)-K(+) pump occurs via a shared downstream oxidative signaling pathway involving NADPH oxidase activation and glutathionylation of the pump beta(1) subunit.