WorldWideScience

Sample records for susceptibility-induced signal loss

  1. Restoring susceptibility induced MRI signal loss in rat brain at 9.4 T: A step towards whole brain functional connectivity imaging.

    Directory of Open Access Journals (Sweden)

    Rupeng Li

    Full Text Available The aural cavity magnetic susceptibility artifact leads to significant echo planar imaging (EPI signal dropout in rat deep brain that limits acquisition of functional connectivity fcMRI data. In this study, we provide a method that recovers much of the EPI signal in deep brain. Needle puncture introduction of a liquid-phase fluorocarbon into the middle ear allows acquisition of rat fcMRI data without signal dropout. We demonstrate that with seeds chosen from previously unavailable areas, including the amygdala and the insular cortex, we are able to acquire large scale networks, including the limbic system. This tool allows EPI-based neuroscience and pharmaceutical research in rat brain using fcMRI that was previously not feasible.

  2. Inflammatory signaling induced bone loss.

    Science.gov (United States)

    Goldring, Steven R

    2015-11-01

    A broad spectrum of inflammatory disorders have the capacity to target the skeleton and to de-regulate the processes of physiological bone remodeling. This review will focus on the systemic inflammatory rheumatologic disorders, which target articular and peri-articular bone tissues. Many of these disorders also affect extra-articular tissues and organs, and in addition, have the capacity to produce systemic bone loss and increased risk of osteoporotic fractures. Attention will focus on rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and the seronegative spondyloarthropathies (SpAs), which include ankylosing spondylitis (AS), reactive arthritis (formerly designated as Reiter's syndrome), the arthritis of inflammatory bowel disease, juvenile onset spondyloarthropathy and psoriatic arthritis. The discussion will principally focus on RA, which is a prototypical model of an inflammatory disorder that de-regulates bone remodeling, but also will review the other forms of inflammatory joint disease to highlight the differential effects of inflammation on bone remodeling in these conditions. This article is part of a Special Issue entitled "Muscle Bone Interactions". Copyright © 2015 Elsevier Inc. All rights reserved.

  3. A simple statistical signal loss model for deep underground garage

    DEFF Research Database (Denmark)

    Nguyen, Huan Cong; Gimenez, Lucas Chavarria; Kovacs, Istvan

    2016-01-01

    In this paper we address the channel modeling aspects for a deep-indoor scenario with extreme coverage conditions in terms of signal losses, namely underground garage areas. We provide an in-depth analysis in terms of path loss (gain) and large scale signal shadowing, and a propose simple...

  4. Hearing Loss Signals Need for Diagnosis

    Science.gov (United States)

    ... of hearing loss are related to aging and exposure to loud noises, and a hearing aid, or frequently one for ... Mann. “There are sometimes problems with a whistling noise from the hearing aid ... will work through with you.” Aids Versus Amplifiers Mann adds ...

  5. determination of gsm determination of gsm signal penetration loss

    African Journals Online (AJOL)

    eobe

    A Samsung Galaxy GT-35000 mobile phone with RF signal tracker software installed in it was used and the results shows an average loss of. 10.62dBm, and 4.25dBm for the concrete and block buildings, respectively. Despite the fact that their measurements considered only concrete and block walls, there results did not ...

  6. Signal-to-noise ratio losses in full spectrum combining of signals with a downconverted subcarrier

    Science.gov (United States)

    Feria, Y.; Statman, J.

    1993-01-01

    This article presents the results of the signal-to-noise ratio loss in the process of full spectrum combining of signals with a downconverted subcarrier under imperfect conditions. These imperfect conditions not only include the misalignment of the carrier, the subcarrier, and the symbols, but they also include the nonideal filtering in the subcarrier downconversion process, the cutoff of the data bandwidth, and the distortion in signal waveform.

  7. Correlation between a loss of auxin signaling and a loss of proliferation in maize antipodal cells

    Directory of Open Access Journals (Sweden)

    Antony Mathai Chettoor

    2015-03-01

    Full Text Available The plant life cycle alternates between two genetically active generations: the diploid sporophyte and the haploid gametophyte. In angiosperms the gametophytes are sexually dimorphic and consist of only a few cells. The female gametophyte, or embryo sac, is comprised of four cell types: two synergids, an egg cell, a central cell, and a variable number of antipodal cells. In some species the antipodal cells are indistinct and fail to proliferate, so many aspects of antipodal cell function and development have been unclear. In maize and many other grasses, the antipodal cells proliferate to produce a highly distinct cluster at the chalazal end of the embryo sac that persists at the apex of the endosperm after fertilization. The antipodal cells are a site of auxin accumulation in the maize embryo sac. Analysis of different families of genes involved in auxin biosynthesis, distribution, and signaling for expression in the embryo sac demonstrates that all steps are expressed within the embryo sac. In contrast to auxin signaling, cytokinin signaling is absent in the embryo sac and instead occurs adjacent to but outside of the antipodal cells. Mutant analysis shows a correlation between a loss of auxin signaling and a loss of proliferation of the antipodal cells. The leaf polarity mutant Laxmidrib1 causes a lack of antipodal cell proliferation coupled with a loss of DR5 and PIN1a expression in the antipodal cells.

  8. determination of gsm determination of gsm signal penetration loss

    African Journals Online (AJOL)

    eobe

    link. Measurements of two existing GSM Operators' signals level were made outside and inside two selected buildings- concrete and block, which represent the prevalent building types in Orhuwhorun,. Delta State, Nigeria. A Samsung Galaxy GT-35000 mobile phone with RF signal tracker software installed in it was used ...

  9. Secreted Wnt Signaling Inhibitors in Disuse-Induced Bone Loss

    Science.gov (United States)

    2014-07-01

    other peripheral nerve injuries that  induce  paralysis.  Disuse  osteoporosis  is a com‐ mon sequelae of spinal cord injury (SCI) an peripheral nerve damage...AND SUBTITLE Secreted Wnt inhibitors in disuse- induced bone loss 5a. CONTRACT NUMBER 5b. GRANT NUMBER 6. AUTHOR(S) Alexander G. Robling, PhD...preventing paralysis- induced bone loss. In the first series, adult female mice were subjected to unilateral Botox- induced muscle paralysis of the

  10. Subband coding of digital audio signals without loss of quality

    NARCIS (Netherlands)

    Veldhuis, Raymond N.J.; Breeuwer, Marcel; van de Waal, Robbert

    1989-01-01

    A subband coding system for high quality digital audio signals is described. To achieve low bit rates at a high quality level, it exploits the simultaneous masking effect of the human ear. It is shown how this effect can be used in an adaptive bit-allocation scheme. The proposed approach has been

  11. Coronary artery stent mimicking intracardiac thrombus on cardiac magnetic resonance imaging due to signal loss

    DEFF Research Database (Denmark)

    Qayyum, Abbas Ali; Vejlstrup, Niels Grove; Ahtarovski, Kiril Aleksov

    2012-01-01

    Since the introduction of percutaneous coronary intervention for coronary artery disease, thousands of patients have been treated with the implantation of coronary stents. Moreover, several of the patients with coronary stent undergo cardiac magnetic resonance (CMR) imaging every year. This case ...... the signal loss on MRI associated with implanted metallic devices is known, we report a case where an implanted coronary stent in the left circumflex artery led to an intracardiac signal loss mimicking intracardiac thrombus/tumor....

  12. Signal-to-Noise ratio and design complexity based on Unified Loss ...

    African Journals Online (AJOL)

    Taguchi's quality loss function for larger-the-better performance characteristics uses a reciprocal transformation to compute quality loss. This paper suggests that reciprocal transformation unnecessarily complicates and may distort results. Examples of this distortion include the signal-to-noise ratio based on mean squared ...

  13. Symbol signal-to-noise ratio loss in square-wave subcarrier downconversion

    Science.gov (United States)

    Feria, Y.; Statman, J.

    1993-01-01

    This article presents the simulated results of the signal-to-noise ratio (SNR) loss in the process of a square-wave subcarrier down conversion. In a previous article, the SNR degradation was evaluated at the output of the down converter based on the signal and noise power change. Unlike in the previous article, the SNR loss is defined here as the difference between the actual and theoretical symbol SNR's for the same symbol-error rate at the output of the symbol matched filter. The results show that an average SNR loss of 0.3 dB can be achieved with tenth-order infinite impulse response (IIR) filters. This loss is a 0.2-dB increase over the SNR degradation in the previous analysis where neither the signal distortion nor the symbol detector was considered.

  14. Effect of extreme data loss on heart rate signals quantified by entropy analysis

    Science.gov (United States)

    Li, Yu; Wang, Jun; Li, Jin; Liu, Dazhao

    2015-02-01

    The phenomenon of data loss always occurs in the analysis of large databases. Maintaining the stability of analysis results in the event of data loss is very important. In this paper, we used a segmentation approach to generate a synthetic signal that is randomly wiped from data according to the Gaussian distribution and the exponential distribution of the original signal. Then, the logistic map is used as verification. Finally, two methods of measuring entropy-base-scale entropy and approximate entropy-are comparatively analyzed. Our results show the following: (1) Two key parameters-the percentage and the average length of removed data segments-can change the sequence complexity according to logistic map testing. (2) The calculation results have preferable stability for base-scale entropy analysis, which is not sensitive to data loss. (3) The loss percentage of HRV signals should be controlled below the range (p = 30 %), which can provide useful information in clinical applications.

  15. Altered neural reward and loss processing and prediction error signalling in depression

    Science.gov (United States)

    Ubl, Bettina; Kuehner, Christine; Kirsch, Peter; Ruttorf, Michaela

    2015-01-01

    Dysfunctional processing of reward and punishment may play an important role in depression. However, functional magnetic resonance imaging (fMRI) studies have shown heterogeneous results for reward processing in fronto-striatal regions. We examined neural responsivity associated with the processing of reward and loss during anticipation and receipt of incentives and related prediction error (PE) signalling in depressed individuals. Thirty medication-free depressed persons and 28 healthy controls performed an fMRI reward paradigm. Regions of interest analyses focused on neural responses during anticipation and receipt of gains and losses and related PE-signals. Additionally, we assessed the relationship between neural responsivity during gain/loss processing and hedonic capacity. When compared with healthy controls, depressed individuals showed reduced fronto-striatal activity during anticipation of gains and losses. The groups did not significantly differ in response to reward and loss outcomes. In depressed individuals, activity increases in the orbitofrontal cortex and nucleus accumbens during reward anticipation were associated with hedonic capacity. Depressed individuals showed an absence of reward-related PEs but encoded loss-related PEs in the ventral striatum. Depression seems to be linked to blunted responsivity in fronto-striatal regions associated with limited motivational responses for rewards and losses. Alterations in PE encoding might mirror blunted reward- and enhanced loss-related associative learning in depression. PMID:25567763

  16. Wavelength conversion of QAM signals in a low loss CMOS compatible spiral waveguide

    Science.gov (United States)

    Da Ros, Francesco; Porto da Silva, Edson; Zibar, Darko; Chu, Sai T.; Little, Brent E.; Morandotti, Roberto; Galili, Michael; Moss, David J.; Oxenløwe, Leif K.

    2017-04-01

    We demonstrate wavelength conversion of quadrature amplitude modulation (QAM) signals, including 32-GBd quadrature phase-shift keying and 10-GBd 16-QAM, in a 50-cm long high index doped glass spiral waveguide. The quality of the generated idlers for up to 20 nm of wavelength shift is sufficient to achieve a BER performance below the hard decision forward error correction threshold BER performance (<3.8 × 103), with an optical signal-to-noise ratio penalty of less than 0.3 dB compared to the original signal. Our results confirm that this is a promising platform for nonlinear optical signal processing, as a result of both very low linear propagation loss (<0.07 dB/cm) and a large material bandgap, which in turn ensures negligible nonlinear loss at telecom wavelengths.

  17. Wavelength conversion of QAM signals in a low loss CMOS compatible spiral waveguide

    Directory of Open Access Journals (Sweden)

    Francesco Da Ros

    2017-04-01

    Full Text Available We demonstrate wavelength conversion of quadrature amplitude modulation (QAM signals, including 32-GBd quadrature phase-shift keying and 10-GBd 16-QAM, in a 50-cm long high index doped glass spiral waveguide. The quality of the generated idlers for up to 20 nm of wavelength shift is sufficient to achieve a BER performance below the hard decision forward error correction threshold BER performance (<3.8 × 103, with an optical signal-to-noise ratio penalty of less than 0.3 dB compared to the original signal. Our results confirm that this is a promising platform for nonlinear optical signal processing, as a result of both very low linear propagation loss (<0.07 dB/cm and a large material bandgap, which in turn ensures negligible nonlinear loss at telecom wavelengths.

  18. Loss of Merlin induces metabolomic adaptation that engages dependence on Hedgehog signaling.

    Science.gov (United States)

    Das, Shamik; Jackson, William P; Prasain, Jeevan K; Hanna, Ann; Bailey, Sarah K; Tucker, J Allan; Bae, Sejong; Wilson, Landon S; Samant, Rajeev S; Barnes, Stephen; Shevde, Lalita A

    2017-01-23

    The tumor suppressor protein Merlin is proteasomally degraded in breast cancer. We undertook an untargeted metabolomics approach to discern the global metabolomics profile impacted by Merlin in breast cancer cells. We discerned specific changes in glutathione metabolites that uncovered novel facets of Merlin in impacting the cancer cell metabolome. Concordantly, Merlin loss increased oxidative stress causing aberrant activation of Hedgehog signaling. Abrogation of GLI-mediated transcription activity compromised the aggressive phenotype of Merlin-deficient cells indicating a clear dependence of cells on Hedgehog signaling. In breast tumor tissues, GLI1 expression enhanced tissue identification and discriminatory power of Merlin, cumulatively presenting a powerful substantiation of the relationship between these two proteins. We have uncovered, for the first time, details of the tumor cell metabolomic portrait modulated by Merlin, leading to activation of Hedgehog signaling. Importantly, inhibition of Hedgehog signaling offers an avenue to target the vulnerability of tumor cells with loss of Merlin.

  19. Estimation of fuel loss due to idling of vehicles at a signalized intersection in Chennai, India

    Science.gov (United States)

    Vasantha Kumar, S.; Gulati, Himanshu; Arora, Shivam

    2017-11-01

    The vehicles while waiting at signalized intersections are generally found to be in idling condition, i.e., not switching off their vehicles during red times. This phenomenon of idling of vehicles during red times at signalized intersections may lead to huge economic loss as lot of fuel is consumed by vehicles when they are in idling condition. The situation may even be worse in countries like India as different vehicle types consume varying amount of fuel. Only limited studies have been reported on estimation of fuel loss due to idling of vehicles in India. In the present study, one of the busy intersections in Chennai, namely, Tidel Park Junction in Rajiv Gandhi salai was considered. Data collection was carried out in one approach road of the intersection during morning and evening peak hours on a typical working day by manually noting down the red timings of each cycle and the corresponding number of two-wheelers, three-wheelers, passenger cars, light commercial vehicles (LCV) and heavy motorized vehicles (HMV) that were in idling mode. Using the fuel consumption values of various vehicles types suggested by Central Road Research Institute (CRRI), the total fuel loss during the study period was found to be Rs. 4,93,849/-. The installation of red timers, synchronization of signals, use of non-motorized transport for short trips and public awareness are some of the measures which government need to focus to save the fuel wasted at signalized intersections in major cities of India.

  20. Relationship Among Signal Fidelity, Hearing Loss, and Working Memory for Digital Noise Suppression.

    Science.gov (United States)

    Arehart, Kathryn; Souza, Pamela; Kates, James; Lunner, Thomas; Pedersen, Michael Syskind

    2015-01-01

    This study considered speech modified by additive babble combined with noise-suppression processing. The purpose was to determine the relative importance of the signal modifications, individual peripheral hearing loss, and individual cognitive capacity on speech intelligibility and speech quality. The participant group consisted of 31 individuals with moderate high-frequency hearing loss ranging in age from 51 to 89 years (mean = 69.6 years). Speech intelligibility and speech quality were measured using low-context sentences presented in babble at several signal-to-noise ratios. Speech stimuli were processed with a binary mask noise-suppression strategy with systematic manipulations of two parameters (error rate and attenuation values). The cumulative effects of signal modification produced by babble and signal processing were quantified using an envelope-distortion metric. Working memory capacity was assessed with a reading span test. Analysis of variance was used to determine the effects of signal processing parameters on perceptual scores. Hierarchical linear modeling was used to determine the role of degree of hearing loss and working memory capacity in individual listener response to the processed noisy speech. The model also considered improvements in envelope fidelity caused by the binary mask and the degradations to envelope caused by error and noise. The participants showed significant benefits in terms of intelligibility scores and quality ratings for noisy speech processed by the ideal binary mask noise-suppression strategy. This benefit was observed across a range of signal-to-noise ratios and persisted when up to a 30% error rate was introduced into the processing. Average intelligibility scores and average quality ratings were well predicted by an objective metric of envelope fidelity. Degree of hearing loss and working memory capacity were significant factors in explaining individual listener's intelligibility scores for binary mask processing

  1. Effects of position, orientation, and metal loss on GPR signals from structural rebar

    Science.gov (United States)

    Eisenmann, David; Margetan, Frank J.; Chiou, C.-P.; Ellis, Shelby; Huang, Tongge; Tan, Jern Yang

    2017-02-01

    Past experimental work on a highway bridge in central Iowa suggested that ground penetrating radar (GPR) signals could possibly be used to differentiate intact rebar from those having substantial metal loss due to corrosion. That study made use of the amplitudes of GPR signals reflected by rebar, as obtained using a commercial instrument operated in pulse/echo mode. Many factors can contribute to the strength of the echo seen from a given rebar, including the rebar's length, its distance from and tilt angle relative to the antenna, and the location and size of the metal-loss region. In this paper we systematically investigate these geometric effects. We begin with measurements of reflected signals where only an air layer separates the antenna from the rebar. There, using standard ½-inch diameter rebar, the GPR signal is systematically studied as a function of the length of the rebar, the stand-off distance from the antenna, the rebar tilt angle, and the size of the metal-loss region. The metal loss region is conveniently simulated by taking two parallel and abutting rebar lengths and pulling them apart to introduce a small gap between them. The "in air" measurements indicate that that GPR signal amplitude is quite sensitive to material loss, but care must be taken to compensate for effects due to rebar depth and orientation. In addition one must avoid working in regimes where wave interference effects can skew the amplitudes of rebar signals. For example introducing a one-inch gap into a long straight rebar can cause the signal reflected from the rebar to either rise or fall depending on the location of the gap relative to the antenna housing. After summarizing the measurements in air, we discuss efforts to extend the study to rebar embedded in concrete. One idea being explored is the use of a powdered "phantom" material (having GPR properties similar to concrete) which can be sandwiched between two concrete blocks. The rebar can then be inserted into the powder

  2. T1-weighted MRI shows stage-dependent substantia nigra signal loss in Parkinson's disease.

    Science.gov (United States)

    Schwarz, Stefan T; Rittman, Timothy; Gontu, Vamsi; Morgan, Paul S; Bajaj, Nin; Auer, Dorothee P

    2011-08-01

    Depigmentation of the substantia nigra is a conspicuous pathological feature of Parkinson's disease and related to a loss of neuromelanin. Similar to melanin, neuromelanin has paramagnetic properties resulting in signal increase on specific T1-weighted magnetic resonance imaging. The aim of this study was to assess signal changes in the substantia nigra in patients with Parkinson's disease using an optimized neuromelanin-sensitive T1 scan. Ten patients with Parkinson's disease and 12 matched controls underwent high-resolution T1-weighted magnetic resonance imaging with magnetization transfer effect at 3T. The size and signal intensity of the substantia nigra pars compacta were determined as the number of pixels with signal intensity higher than background signal intensity+3 standard deviations and regional contrast ratio. Patients were subclassified as early stage (n=6) and late stage (n=4) using the Unified Parkinson's Disease Rating Scale and the Hoehn and Yahr Parkinson's disease staging scale. The T1 hyperintense area in the substantia nigra was substantially smaller in patients compared with controls (-60%, Pearly-stage disease (-47%). We present preliminary findings using a modified T1-weighted magnetic resonance imaging technique showing stage-dependent substantia nigra signal reduction in Parkinson's disease as a putative marker of neuromelanin loss. Our data suggest that reduction in the size of neuromelanin-rich substantia nigra correlates well with postmortem observations of dopaminergic neuron loss. Further validation of our results could potentially lead to development of a new biomarker of disease progression in Parkinson's disease. Copyright © 2011 Movement Disorder Society.

  3. Loss of Signal, Aeromedical Lessons Learned from the STS-107 Columbia Space Shuttle Mishap

    Science.gov (United States)

    Stepaniak, Phillip C.; Patlach, Robert

    2014-01-01

    Loss of Signal, a NASA publication to be available in May 2014 presents the aeromedical lessons learned from the Columbia accident that will enhance crew safety and survival on human space flight missions. These lessons were presented to limited audiences at three separate Aerospace Medical Association (AsMA) conferences: in 2004 in Anchorage, Alaska, on the causes of the accident; in 2005 in Kansas City, Missouri, on the response, recovery, and identification aspects of the investigation; and in 2011, again in Anchorage, Alaska, on future implications for human space flight. As we embark on the development of new spacefaring vehicles through both government and commercial efforts, the NASA Johnson Space Center Human Health and Performance Directorate is continuing to make this information available to a wider audience engaged in the design and development of future space vehicles. Loss of Signal summarizes and consolidates the aeromedical impacts of the Columbia mishap process-the response, recovery, identification, investigative studies, medical and legal forensic analysis, and future preparation that are needed to respond to spacecraft mishaps. The goal of this book is to provide an account of the aeromedical aspects of the Columbia accident and the investigation that followed, and to encourage aerospace medical specialists to continue to capture information, learn from it, and improve procedures and spacecraft designs for the safety of future crews. This poster presents an outline of Loss of Signal contents and highlights from each of five sections - the mission and mishap, the response, the investigation, the analysis and the future.

  4. Predicting long-term weight loss maintenance in previously overweight women: a signal detection approach.

    Science.gov (United States)

    Santos, Inês; Mata, Jutta; Silva, Marlene N; Sardinha, Luís B; Teixeira, Pedro J

    2015-05-01

    Examine psychological and behavioral predictors of 3-year weight loss maintenance in women. Participants were 154 women in a 1-year randomized controlled trial on weight management with a 2-year follow-up. Signal detection analyses identified behavioral and psychological variables that best predicted 5% and 10% weight loss at 3 years. Women with better body image were more likely to have lost ≥5% weight at 3 years (P women with poor body image but higher motivation were more likely to maintain weight loss than women with poor body image and lower motivation (P Women with high exercise autonomous motivation were three times more likely to have lost ≥10% weight than were those with lower autonomous motivation (P women with lower autonomous motivation, perceiving fewer exercise barriers was somewhat compensatory: these women were more likely to maintain weight loss than women with lower autonomy but more perceived barriers (P women, improving body image and increasing autonomous and intrinsic motivation for exercise likely promotes clinically significant long-term weight loss maintenance. Decreasing perceived exercise barriers is another promising intervention target. © 2015 The Obesity Society.

  5. Loss of FTO antagonises Wnt signaling and leads to developmental defects associated with ciliopathies.

    Directory of Open Access Journals (Sweden)

    Daniel P S Osborn

    Full Text Available Common intronic variants in the Human fat mass and obesity-associated gene (FTO are found to be associated with an increased risk of obesity. Overexpression of FTO correlates with increased food intake and obesity, whilst loss-of-function results in lethality and severe developmental defects. Despite intense scientific discussions around the role of FTO in energy metabolism, the function of FTO during development remains undefined. Here, we show that loss of Fto leads to developmental defects such as growth retardation, craniofacial dysmorphism and aberrant neural crest cells migration in Zebrafish. We find that the important developmental pathway, Wnt, is compromised in the absence of FTO, both in vivo (zebrafish and in vitro (Fto(-/- MEFs and HEK293T. Canonical Wnt signalling is down regulated by abrogated β-Catenin translocation to the nucleus whilst non-canonical Wnt/Ca(2+ pathway is activated via its key signal mediators CaMKII and PKCδ. Moreover, we demonstrate that loss of Fto results in short, absent or disorganised cilia leading to situs inversus, renal cystogenesis, neural crest cell defects and microcephaly in Zebrafish. Congruently, Fto knockout mice display aberrant tissue specific cilia. These data identify FTO as a protein-regulator of the balanced activation between canonical and non-canonical branches of the Wnt pathway. Furthermore, we present the first evidence that FTO plays a role in development and cilia formation/function.

  6. Printed silver nanowire antennas with low signal loss at high-frequency radio.

    Science.gov (United States)

    Komoda, Natsuki; Nogi, Masaya; Suganuma, Katsuaki; Kohno, Kazuo; Akiyama, Yutaka; Otsuka, Kanji

    2012-05-21

    Silver nanowires are printable and conductive, and are believed to be promising materials in the field of printed electronics. However, the resistivity of silver nanowire printed lines is higher than that of metallic particles or flakes even when sintered at high temperatures of 100-400 °C. Therefore, their applications have been limited to the replacement of transparent electrodes made from high-resistivity materials, such as doped metallic oxides, conductive polymers, carbon nanotubes, or graphenes. Here we report that using printed silver nanowire lines, signal losses obtained in the high-frequency radio were lower than those obtained using etched copper foil antennas, because their surfaces were much smoother than those of etched copper foil antennas. This was the case even though the resistivity of silver nanowire lines was 43-71 μΩ cm, which is much higher than that of etched copper foil (2 μΩ cm). When printed silver nanowire antennas were heated at 100 °C, they achieved signal losses that were much lower than those of silver paste antennas comprising microparticles, nanoparticles, and flakes. Furthermore, using a low temperature process, we succeeded in remotely controlling a commercialized radio-controlled car by transmitting a 2.45 GHz signal via a silver nanowire antenna printed on a polyethylene terephthalate film.

  7. The classification for "equilibrium triad" sensory loss based on sEMG signals of calf muscles.

    Science.gov (United States)

    Hairong Yu; Kairui Guo; Jie Luo; Kai Cao; Nguyen, Hung T; Su, Steven W

    2017-07-01

    Surface Electromyography (sEMG) has been commonly applied for analysing the electrical activities of skeletal muscles. The sensory system of maintaining posture balance includes vision, proprioception and vestibular senses. In this work, an attempt is made to classify whether the body is missing one of the sense during balance control by using sEMG signals. A trial of combination with different features and muscles is also developed. The results demonstrate that the classification accuracy between vision loss and the normal condition is higher than the one between vestibular sense loss and normal condition. When using different features and muscles, the impact on classification results is also different. The outcomes of this study could aid the development of sEMG based classification for the function of sensory systems during human balance movement.

  8. False alarms: How early warning signals falsely predict abrupt sea ice loss

    Science.gov (United States)

    Wagner, Till J. W.; Eisenman, Ian

    2016-04-01

    Uncovering universal early warning signals for critical transitions has become a coveted goal in diverse scientific disciplines, ranging from climate science to financial mathematics. There has been a flurry of recent research proposing such signals, with increasing autocorrelation and increasing variance being among the most widely discussed candidates. A number of studies have suggested that increasing autocorrelation alone may suffice to signal an impending transition, although some others have questioned this. Here we consider variance and autocorrelation in the context of sea ice loss in an idealized model of the global climate system. The model features no bifurcation, nor increased rate of retreat, as the ice disappears. Nonetheless, the autocorrelation of summer sea ice area is found to increase in a global warming scenario. The variance, by contrast, decreases. A simple physical mechanism is proposed to explain the occurrence of increasing autocorrelation but not variance when there is no approaching bifurcation. Additionally, a similar mechanism is shown to allow an increase in both indicators with no physically attainable bifurcation. This implies that relying on autocorrelation and variance as early warning signals can raise false alarms in the climate system, warning of "tipping points" that are not actually there.

  9. Early Warning Signals for Abrupt Change Raise False Alarm During Sea Ice Loss

    Science.gov (United States)

    Wagner, T. J. W.; Eisenman, I.

    2015-12-01

    Uncovering universal early warning signals for critical transitions has become a coveted goal in diverse scientific disciplines, ranging from climate science to financial mathematics. There has been a flurry of recent research proposing such signals, with increasing autocorrelation and increasing variance being among the most widely discussed candidates. A number of studies have suggested that increasing autocorrelation alone may suffice to signal an impending transition, although some others have questioned this. Here, we consider variance and autocorrelation in the context of sea ice loss in an idealized model of the global climate system. The model features no bifurcation, nor increased rate of retreat, as the ice disappears. Nonetheless, the autocorrelation of summer sea ice area is found to increase with diminishing sea ice cover in a global warming scenario. The variance, by contrast, decreases. A simple physical mechanism is proposed to explain the occurrence of increasing autocorrelation but not variance in the model when there is no approaching bifurcation. Additionally, a similar mechanism is shown to allow an increase in both indicators with no physically attainable bifurcation. This implies that relying on autocorrelation and variance as early warning signals can raise false alarms in the climate system, warning of "tipping points" that are not actually there.

  10. Loss of Acetylcholine Signaling Reduces Cell Clearance Deficiencies in Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Sérgio M Pinto

    Full Text Available The ability to eliminate undesired cells by apoptosis is a key mechanism to maintain organismal health and homeostasis. Failure to clear apoptotic cells efficiently can cause autoimmune diseases in mammals. Genetic studies in Caenorhabditis elegans have greatly helped to decipher the regulation of apoptotic cell clearance. In this study, we show that the loss of levamisole-sensitive acetylcholine receptor, but not of a typical neuronal acetylcholine receptor causes a reduction in the number of persistent cell corpses in worms suffering from an engulfment deficiency. This reduction is not caused by impaired or delayed cell death but rather by a partial restoration of the cell clearance capacity. Mutants in acetylcholine turn-over elicit a similar phenotype, implying that acetylcholine signaling is the process responsible for these observations. Surprisingly, tissue specific RNAi suggests that UNC-38, a major component of the levamisole-sensitive receptor, functions in the dying germ cell to influence engulfment efficiency. Animals with loss of acetylcholine receptor exhibit a higher fraction of cell corpses positive for the "eat-me" signal phosphatidylserine. Our results suggest that modulation by ion channels of ion flow across plasma membrane in dying cells can influence the dynamics of phosphatidylserine exposure and thus clearance efficiency.

  11. Loss of Signal, Aeromedical Lessons Learned for the STS-I07 Columbia Space Shuttle Mishap

    Science.gov (United States)

    Patlach, Robert; Stepaniak, Philip C.; Lane, Helen W.

    2014-01-01

    Loss of Signal, a NASA publication to be available in May 2014, presents the aeromedical lessons learned from the Columbia accident that will enhance crew safety and survival on human space flight missions. These lessons were presented to limited audiences at three separate Aerospace Medical Association (AsMA) conferences: in 2004 in Anchorage, Alaska, on the causes of the accident; in 2005 in Kansas City, Missouri, on the response, recovery, and identification aspects of the investigation; and in 2011, again in Anchorage, Alaska, on future implications for human space flight. As we embark on the development of new spacefaring vehicles through both government and commercial efforts, the NASA Johnson Space Center Human Health and Performance Directorate is continuing to make this information available to a wider audience engaged in the design and development of future space vehicles. Loss of Signal summarizes and consolidates the aeromedical impacts of the Columbia mishap process-the response, recovery, identification, investigative studies, medical and legal forensic analysis, and future preparation that are needed to respond to spacecraft mishaps. The goals of this book are to provide an account of the aeromedical aspects of the Columbia accident and the investigation that followed, and to encourage aerospace medical specialists to continue to capture information, learn from it, and improve procedures and spacecraft designs for the safety of future crews.

  12. Data Fusion to Develop a Driver Drowsiness Detection System with Robustness to Signal Loss

    Directory of Open Access Journals (Sweden)

    Sajjad Samiee

    2014-09-01

    Full Text Available This study proposes a drowsiness detection approach based on the combination of several different detection methods, with robustness to the input signal loss. Hence, if one of the methods fails for any reason, the whole system continues to work properly. To choose correct combination of the available methods and to utilize the benefits of methods of different categories, an image processing-based technique as well as a method based on driver-vehicle interaction is used. In order to avoid driving distraction, any use of an intrusive method is prevented. A driving simulator is used to gather real data and then artificial neural networks are used in the structure of the designed system. Several tests were conducted on twelve volunteers while their sleeping situations during one day prior to the tests, were fully under control. Although the impact of the proposed system on the improvement of the detection accuracy is not remarkable, the results indicate the main advantages of the system are the reliability of the detections and robustness to the loss of the input signals. The high reliability of the drowsiness detection systems plays an important role to reduce drowsiness related road accidents and their associated costs.

  13. Data fusion to develop a driver drowsiness detection system with robustness to signal loss.

    Science.gov (United States)

    Samiee, Sajjad; Azadi, Shahram; Kazemi, Reza; Nahvi, Ali; Eichberger, Arno

    2014-09-25

    This study proposes a drowsiness detection approach based on the combination of several different detection methods, with robustness to the input signal loss. Hence, if one of the methods fails for any reason, the whole system continues to work properly. To choose correct combination of the available methods and to utilize the benefits of methods of different categories, an image processing-based technique as well as a method based on driver-vehicle interaction is used. In order to avoid driving distraction, any use of an intrusive method is prevented. A driving simulator is used to gather real data and then artificial neural networks are used in the structure of the designed system. Several tests were conducted on twelve volunteers while their sleeping situations during one day prior to the tests, were fully under control. Although the impact of the proposed system on the improvement of the detection accuracy is not remarkable, the results indicate the main advantages of the system are the reliability of the detections and robustness to the loss of the input signals. The high reliability of the drowsiness detection systems plays an important role to reduce drowsiness related road accidents and their associated costs.

  14. Regulators of G protein signaling 12 promotes osteoclastogenesis in bone remodeling and pathological bone loss.

    Science.gov (United States)

    Yuan, X; Cao, J; Liu, T; Li, Y-P; Scannapieco, F; He, X; Oursler, M J; Zhang, X; Vacher, J; Li, C; Olson, D; Yang, S

    2015-12-01

    Regulators of G protein signaling (Rgs) have pivotal roles in controlling various cellular processes, such as cell differentiation. How Rgs proteins regulate osteoclast (OC) differentiation, function and bone homeostasis is poorly understood. It was previously demonstrated that Rgs12, the largest protein in the Rgs family, is predominantly expressed in OCs and regulates OC differentiation in vitro. To further understand the role and mechanism of Rgs12 in OC differentiation and bone diseases in vivo, we created OC-targeted Rgs12 knockout mice by using inducible Mx1-Cre and CD11b-Cre. Deletion of Rgs12 in hematopoietic cells or specifically in OC precursors resulted in increased bone mass with decreased OC numbers. Loss of Rgs12 impaired OC differentiation and function with impaired Ca(2+) oscillations and reduced nuclear factor of activated T cells (NFAT) 2 expression. The introduction of wild-type osteoblasts did not rescue the defective osteoclastogenesis. Ectopic expression of NFAT2 rescued defective OC differentiation in CD11b;Rgs12(fl/fl) cells and promoted normal OC differentiation. Moreover, deletion of Rgs12 significantly inhibited pathological osteoclastogenesis and bone destruction in Rgs12-deficient mice that were subjected to ovariectomy and lipodysaccharide for bone loss. Thus our findings demonstrate that Rgs12 is an important regulator in OC differentiation and function and identify Rgs12 as a potential therapeutic target for osteoporosis and inflammation-induced bone loss.

  15. The impact of moderate sleep loss on neurophysiologic signals during working-memory task performance.

    Science.gov (United States)

    Smith, Michael E; McEvoy, Linda K; Gevins, Alan

    2002-11-01

    This study examined how sleep loss affects neurophysiologic signals related to attention and working memory. Subjective sleepiness, resting-state electroencephalogram, and behavior and electroencephalogram during performance of working-memory tasks were recorded in a within-subject, repeated-measures design. Data collection occurred in a computerized laboratory setting. Sixteen healthy adults (mean age, 26 years; 8 female) Data from alert daytime baseline tests were compared with data from tests during a late-night, extended-wakefulness session that spanned up to 21 hours of sleep deprivation. Alertness measured both subjectively and electrophysiologically decreased monotonically with increasing sleep deprivation. A lack of alertness-related changes in electroencephalographic measures of the overall mental effort exerted during task execution indicated that participants attempted to maintain high levels of performance throughout the late-night tests. Despite such continued effort, responses became slower, more variable, and more error prone within 1 hour after participants' normal time of sleep onset. This behavior failure was accompanied by significant degradation of event-related brain potentials related to the transient focusing of attention. Moderate sleep loss compromises the function of neural circuits critical to subsecond attention allocation during working-memory tasks, even when an effort is made to maintain wakefulness and performance. Multivariate analyses indicate that combinations of working-memory-related behavior and neurophysiologic measures can be sensitive enough to permit reliable detection of such effects of sleep loss in individuals. Similar methods might prove useful for assessment of functional alertness in patients with sleep disorders.

  16. The Loss of TGF-β Signaling Promotes Prostate Cancer Metastasis

    Directory of Open Access Journals (Sweden)

    William H. Tu

    2003-05-01

    Full Text Available In breast and colon cancers, transforming growth factor (TGIF-β signaling initially has an antineoplastic effect, inhibiting tumor growth, but eventually exerts a proneoplastic effect, increasing motility and cancer spread. In prostate cancer, studies using human samples have correlated the loss of the TGIF-β type II receptor (TβRll with higher tumor grade. To determine the effect of an inhibited TGIF-β pathway on prostate cancer, we bred transgenic mice expressing the tumorigenic SV40 large T antigen in the prostate with transgenic mice expressing a dominant negative TβRII mutant (DNIIR in the prostate. Transgene(s and TGIF-β expression were identified in the prostate and decreased protein levels of plasminogen activator inhibitor type I, as a marker for TGIF-β signaling, correlated with expression of the DNIIR. Although the sizes of the neoplastic prostates were not enlarged, increased amounts of metastasis were observed in mice expressing both transgenes compared to age-matched control mice expressing only the large T antigen transgene. Our study demonstrates for the first time that a disruption of TGIF-β signaling in prostate cancer plays a causal role in promoting tumor metastasis.

  17. Recurrent Loss of STING Signaling in Melanoma Correlates with Susceptibility to Viral Oncolysis.

    Science.gov (United States)

    Xia, Tianli; Konno, Hiroyasu; Barber, Glen N

    2016-11-15

    The innate immunoregulator STING stimulates cytokine production in response to the presence of cytosolic DNA, which can arise following DNA damage. Extrinsic STING signaling is also needed for antigen-presenting cells to stimulate antitumor T-cell immunity. Here, we show that STING signaling is recurrently suppressed in melanoma cells, where this event may enable immune escape after DNA damage. Mechanistically, STING signaling was suppressed most frequently by epigenetic silencing of either STING or the cyclic GMP-AMP synthase, which generates STING-activating cyclic dinucleotides after binding cytosolic DNA species. Loss of STING function rendered melanoma cells unable to produce type I IFN and other immune cytokines after exposure to cytosolic DNA species. Consequently, such cells were highly susceptible to infection with DNA viruses including HSV1, a variant of which is being developed presently as a therapeutic oncolytic virus [talimogene laherparepvec (T-VEC)]. Our findings provide insight into the basis for susceptibility to viral oncolysis by agents such as HSV1. Cancer Res; 76(22); 6747-59. ©2016 AACR. ©2016 American Association for Cancer Research.

  18. Effect of extreme data loss on long-range correlated and anticorrelated signals quantified by detrended fluctuation analysis.

    Science.gov (United States)

    Ma, Qianli D Y; Bartsch, Ronny P; Bernaola-Galván, Pedro; Yoneyama, Mitsuru; Ivanov, Plamen Ch

    2010-03-01

    Detrended fluctuation analysis (DFA) is an improved method of classical fluctuation analysis for nonstationary signals where embedded polynomial trends mask the intrinsic correlation properties of the fluctuations. To better identify the intrinsic correlation properties of real-world signals where a large amount of data is missing or removed due to artifacts, we investigate how extreme data loss affects the scaling behavior of long-range power-law correlated and anticorrelated signals. We introduce a segmentation approach to generate surrogate signals by randomly removing data segments from stationary signals with different types of long-range correlations. The surrogate signals we generate are characterized by four parameters: (i) the DFA scaling exponent alpha of the original correlated signal u(i) , (ii) the percentage p of the data removed from u(i) , (iii) the average length mu of the removed (or remaining) data segments, and (iv) the functional form P(l) of the distribution of the length l of the removed (or remaining) data segments. We find that the global scaling exponent of positively correlated signals remains practically unchanged even for extreme data loss of up to 90%. In contrast, the global scaling of anticorrelated signals changes to uncorrelated behavior even when a very small fraction of the data is lost. These observations are confirmed on two examples of real-world signals: human gait and commodity price fluctuations. We further systematically study the local scaling behavior of surrogate signals with missing data to reveal subtle deviations across scales. We find that for anticorrelated signals even 10% of data loss leads to significant monotonic deviations in the local scaling at large scales from the original anticorrelated to uncorrelated behavior. In contrast, positively correlated signals show no observable changes in the local scaling for up to 65% of data loss, while for larger percentage of data loss, the local scaling shows

  19. Loss of FGF-dependent mesoderm identity and rise of endogenous retinoid signalling determine cessation of body axis elongation.

    Science.gov (United States)

    Olivera-Martinez, Isabel; Harada, Hidekiyo; Halley, Pamela A; Storey, Kate G

    2012-01-01

    The endogenous mechanism that determines vertebrate body length is unknown but must involve loss of chordo-neural-hinge (CNH)/axial stem cells and mesoderm progenitors in the tailbud. In early embryos, Fibroblast growth factor (FGF) maintains a cell pool that progressively generates the body and differentiation onset is driven by retinoid repression of FGF signalling. This raises the possibility that FGF maintains key tailbud cell populations and that rising retinoid activity underlies cessation of body axis elongation. Here we show that sudden loss of the mesodermal gene (Brachyury) from CNH and the mesoderm progenitor domain correlates with FGF signalling decline in the late chick tailbud. This is accompanied by expansion of neural gene expression and a similar change in cell fate markers is apparent in the human tailbud. Fate mapping of chick tailbud further revealed that spread of neural gene expression results from continued ingression of CNH-derived cells into the position of the mesoderm progenitor domain. Using gain and loss of function approaches in vitro and in vivo, we then show that attenuation of FGF/Erk signalling mediates this loss of Brachyury upstream of Wnt signalling, while high-level FGF maintains Brachyury and can induce ectopic CNH-like cell foci. We further demonstrate a rise in endogenous retinoid signalling in the tailbud and show that here FGF no longer opposes retinoid synthesis and activity. Furthermore, reduction of retinoid signalling at late stages elevated FGF activity and ectopically maintained mesodermal gene expression, implicating endogenous retinoid signalling in loss of mesoderm identity. Finally, axis termination is concluded by local cell death, which is reduced by blocking retinoid signalling, but involves an FGFR-independent mechanism. We propose that cessation of body elongation involves loss of FGF-dependent mesoderm identity in late stage tailbud and provide evidence that rising endogenous retinoid activity mediates this

  20. Statistical Modeling of Large-Scale Signal Path Loss in Underwater Acoustic Networks

    Directory of Open Access Journals (Sweden)

    Manuel Perez Malumbres

    2013-02-01

    Full Text Available In an underwater acoustic channel, the propagation conditions are known to vary in time, causing the deviation of the received signal strength from the nominal value predicted by a deterministic propagation model. To facilitate a large-scale system design in such conditions (e.g., power allocation, we have developed a statistical propagation model in which the transmission loss is treated as a random variable. By applying repetitive computation to the acoustic field, using ray tracing for a set of varying environmental conditions (surface height, wave activity, small node displacements around nominal locations, etc., an ensemble of transmission losses is compiled and later used to infer the statistical model parameters. A reasonable agreement is found with log-normal distribution, whose mean obeys a log-distance increases, and whose variance appears to be constant for a certain range of inter-node distances in a given deployment location. The statistical model is deemed useful for higher-level system planning, where simulation is needed to assess the performance of candidate network protocols under various resource allocation policies, i.e., to determine the transmit power and bandwidth allocation necessary to achieve a desired level of performance (connectivity, throughput, reliability, etc..

  1. Independence Between Two Channels of Surface Electromyogram Signal to Measure the Loss of Motor Units

    Directory of Open Access Journals (Sweden)

    Arjunan Sridhar P.

    2015-06-01

    Full Text Available This study has investigated the relationship in the connectivity of motor units in surface electromyogram (sEMG of biceps brachii muscle. It is hypothesized that with ageing, there is reduction/loss in number of motor units, leading to reduction in the independence between the channels of the recorded muscle activity. Two channels of sEMG were recorded during three levels of isometric muscle contraction: 50 %, 75 % and 100 % maximal voluntary contraction (MVC. 73 subjects (age range 20-70 participated in the experiments. The independence in channel index (ICI between the two sEMG recording locations was computed using the independent components and Frobenius norm. ANOVA Statistical analysis was performed to test the effect of age (loss of motor units and level of contraction on ICI. The results show that the ICI among the older cohort was significantly lower compared with the younger adults. This research study has shown that the reduction in number of motor units is reflected by the reduction in the ICI of the sEMG signal.

  2. Loss of mesenchymal CSL signaling leads to field cancerization and multifocal epithelial tumors

    Science.gov (United States)

    Hu, Bing; Castillo, Einar; Harewood, Louise; Ostano, Paola; Reymond, Alexandre; Dummer, Reinhard; Raffoul, Wassim; Hoetzenecker, Wolfram; Hofbauer, Günther F. L.; Dotto, G. Paolo

    2012-01-01

    Summary It is currently unclear whether tissue changes surrounding multifocal epithelial tumors are a cause or consequence of cancer. Here, we provide evidence that loss of mesenchymal Notch/CSL signaling causes tissue alterations, including stromal atrophy and inflammation, which precede and are potent triggers for epithelial tumors. Mice carrying a mesenchymal-specific deletion of CSL/RBP-Jκ, a key Notch effector, exhibit spontaneous multifocal keratinocyte tumors that develop after dermal atrophy and inflammation. CSL-deficient dermal fibroblasts promote increased tumor cell proliferation through up-regulation of c-Jun and c-Fos expression and consequently higher levels of diffusible growth factors, inflammatory cytokines, and matrix remodeling enzymes. In human skin samples, stromal fields adjacent to cutaneous squamous cell carcinomas and multifocal premalignant actinic keratosis lesions exhibit decreased Notch/CSL signaling and associated molecular changes. Importantly, these changes in gene expression are also induced by UVA, a known environmental cause of cutaneous field cancerization and skin cancer. PMID:22682244

  3. Multifocal epithelial tumors and field cancerization from loss of mesenchymal CSL signaling.

    Science.gov (United States)

    Hu, Bing; Castillo, Einar; Harewood, Louise; Ostano, Paola; Reymond, Alexandre; Dummer, Reinhard; Raffoul, Wassim; Hoetzenecker, Wolfram; Hofbauer, Günther F L; Dotto, G Paolo

    2012-06-08

    It is currently unclear whether tissue changes surrounding multifocal epithelial tumors are a cause or consequence of cancer. Here, we provide evidence that loss of mesenchymal Notch/CSL signaling causes tissue alterations, including stromal atrophy and inflammation, which precede and are potent triggers for epithelial tumors. Mice carrying a mesenchymal-specific deletion of CSL/RBP-Jκ, a key Notch effector, exhibit spontaneous multifocal keratinocyte tumors that develop after dermal atrophy and inflammation. CSL-deficient dermal fibroblasts promote increased tumor cell proliferation through upregulation of c-Jun and c-Fos expression and consequently higher levels of diffusible growth factors, inflammatory cytokines, and matrix-remodeling enzymes. In human skin samples, stromal fields adjacent to multifocal premalignant actinic keratosis lesions exhibit decreased Notch/CSL signaling and associated molecular changes. Importantly, these changes in gene expression are also induced by UVA, a known environmental cause of cutaneous field cancerization and skin cancer. Copyright © 2012 Elsevier Inc. All rights reserved.

  4. Role of IL-17A signalling in psoriasis and associated bone loss.

    Science.gov (United States)

    Uluçkan, Özge; Wagner, Erwin F

    2016-01-01

    Inflammation is a physiological reaction to tissue injury, pathogen invasion and a natural response to various stress stimuli. Innate and adaptive immune cells are activated and recruited to the site of inflammation to suppress or promote inflammation. The recruitment and activation of immune cells is modulated by cytokines and chemokines, which are regulated by transcription factors, such as AP-1 (Fos/Jun), NF-kB, NFATs and STATs. Moreover, it is now appreciated that chronic inflammation can lead to systemic effects affecting the whole organism by mechanisms which are not well understood.Here we review our recent data obtained from the analyses of psoriasis patient samples as well as from AP-1 (Fos/Jun)-dependent, genetically engineered mouse models. The deletion of two AP-1 factors JunB and c-Jun in an inducible manner in adult mice, specifically in Keratin-5 expressing tissues, leads to a psoriasis-like disease. Importantly, the epidermal proteome of the mutant mice is comparable to psoriasis patient samples. Our analyses revealed that the activation of S100A8/A9-dependent C3 complement as well as a miR-21-dependent TIMP-3/TACE pathway leading to TNF-α shedding, are causally involved in disease development.Epidermal deletion of only JunB in mice leads to chronic skin inflammation with increased levels of pro-inflammatory cytokines and multi-organ involvement. Our recent findings show that chronic skin inflammation induces bone loss through systemic elevated IL-17A signalling. This novel mechanism involves inhibition of osteoblast-mediated bone formation by reduced Wnt signalling with no effect on RANKL-dependent osteoclastic bone resorption. These data have important translational implications; blocking of IL-17A signalling, which is already approved for the treatment of psoriasis, should also be considered to prevent the adverse skeletal consequences of chronic inflammatory diseases.

  5. Prostate cancer induced by loss of Apc is restrained by TGFβ signaling.

    Directory of Open Access Journals (Sweden)

    Glen A Bjerke

    Full Text Available Recent work with mouse models of prostate cancer (CaP has shown that inactivation of TGFβ signaling in prostate epithelium can cooperate with deletion of the Pten tumor suppressor to drive locally aggressive cancer and metastatic disease. Here, we show that inactivating the TGFβ pathway by deleting the gene encoding the TGFβ type II receptor (Tgfbr2 in combination with a deletion of the Apc tumor suppressor gene specifically in mouse prostate epithelium, results in the rapid onset of invasive CaP. Micro-metastases were observed in the lymph nodes and lungs of a proportion of the double mutant mice, whereas no metastases were observed in Apc single mutant mice. Prostate-specific Apc;Tgfbr2 mutants had a lower frequency of metastasis and survived significantly longer than Pten;Tgfbr2 double mutants. However, all Apc;Tgfbr2 mutants developed invasive cancer by 30 weeks of age, whereas invasive cancer was rarely observed in Apc single mutant animals, even by one year of age. Further comparison of the Pten and Apc models of CaP revealed additional differences, including adenosquamous carcinoma in the Apc;Tgfbr2 mutants that was not seen in the Pten model, and a lack of robust induction of the TGFβ pathway in Apc null prostate. In addition to causing high-grade prostate intra-epithelial neoplasia (HGPIN, deletion of either Pten or Apc induced senescence in affected prostate ducts, and this restraint was overcome by loss of Tgfbr2. In summary, this work demonstrates that TGFβ signaling restrains the progression of CaP induced by different tumor suppressor mutations, suggesting that TGFβ signaling exerts a general tumor suppressive effect in prostate.

  6. Erbin loss promotes cancer cell proliferation through feedback activation of Akt-Skp2-p27 signaling

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Hao [Department of Pathophysiology, Institute of Basic Medical Sciences, Beijing 100850 (China); Laboratory of Cellular and Molecular Immunology, Medical School of Henan University, Kaifeng 475004 (China); Song, Yuhua [The Affiliated Hospital of Medical College, Qingdao University, Qingdao (China); Wu, Yan; Guo, Ning [Department of Pathophysiology, Institute of Basic Medical Sciences, Beijing 100850 (China); Ma, Yuanfang [Laboratory of Cellular and Molecular Immunology, Medical School of Henan University, Kaifeng 475004 (China); Qian, Lu, E-mail: mayf@henu.edu.cn [Department of Pathophysiology, Institute of Basic Medical Sciences, Beijing 100850 (China)

    2015-07-31

    Erbin localizes at the basolateral membrane to regulate cell junctions and polarity in epithelial cells. Dysregulation of Erbin has been implicated in tumorigenesis, and yet it is still unclear if and how disrupted Erbin regulates the biological behavior of cancer cells. We report here that depletion of Erbin leads to cancer cell excessive proliferation in vitro and in vivo. Erbin deficiency accelerates S-phase entry by down-regulating CDK inhibitors p21 and p27 via two independent mechanisms. Mechanistically, Erbin loss promotes p27 degradation by enhancing E3 ligase Skp2 activity though augmenting Akt signaling. Interestingly, we also show that Erbin is an unstable protein when the Akt-Skp2 signaling is aberrantly activated, which can be specifically destructed by SCF-Skp2 ligase. Erbin loss facilitates cell proliferation and migration in Skp2-dependent manner. Thus, our finding illustrates a novel negative feedback loop between Erbin and Akt-Skp2 signaling. It suggests disrupted Erbin links polarity loss, hyperproliferation and tumorigenesis. - Highlights: • Erbin loss leads to cancer cell excessive proliferation in vitro and in vivo. • Erbin loss accelerates cell cycle though down-regulating p21 and p27 expression. • Erbin is a novel negative modulator of Akt1-Skp2-p27 signaling pathway. • Our study suggests that Erbin loss contributes to Skp2 oncogenic function.

  7. Transient Inhibition of FGFR2b-ligands signaling leads to irreversible loss of cellular β-catenin organization and signaling in AER during mouse limb development.

    Directory of Open Access Journals (Sweden)

    Soula Danopoulos

    Full Text Available The vertebrate limbs develop through coordinated series of inductive, growth and patterning events. Fibroblast Growth Factor receptor 2b (FGFR2b signaling controls the induction of the Apical Ectodermal Ridge (AER but its putative roles in limb outgrowth and patterning, as well as in AER morphology and cell behavior have remained unclear. We have investigated these roles through graded and reversible expression of soluble dominant-negative FGFR2b molecules at various times during mouse limb development, using a doxycycline/transactivator/tet(O-responsive system. Transient attenuation (≤ 24 hours of FGFR2b-ligands signaling at E8.5, prior to limb bud induction, leads mostly to the loss or truncation of proximal skeletal elements with less severe impact on distal elements. Attenuation from E9.5 onwards, however, has an irreversible effect on the stability of the AER, resulting in a progressive loss of distal limb skeletal elements. The primary consequences of FGFR2b-ligands attenuation is a transient loss of cell adhesion and down-regulation of P63, β1-integrin and E-cadherin, and a permanent loss of cellular β-catenin organization and WNT signaling within the AER. Combined, these effects lead to the progressive transformation of the AER cells from pluristratified to squamous epithelial-like cells within 24 hours of doxycycline administration. These findings show that FGFR2b-ligands signaling has critical stage-specific roles in maintaining the AER during limb development.

  8. Effect of placement of droop based generators in distribution network on small signal stability margin and network loss

    DEFF Research Database (Denmark)

    Dheer, D.K.; Doolla, S.; Bandyopadhyay, S.

    2017-01-01

    For a utility-connected system, issues related to small signal stability with Distributed Generators (DGs) are insignificant due to the presence of a very strong grid. Optimally placed sources in utility connected microgrid system may not be optimal/stable in islanded condition. Among others issues......, small signal stability margin is on the fore. The present research studied the effect of location of droop-controlled DGs on small signal stability margin and network loss on a modified IEEE 13 bus system, an IEEE 33-bus distribution system and a practical 22-bus radial distribution network. A complete...... dynamic model of an islanded microgrid was developed. From stability analysis, the study reports that both location of DGs and choice of droop coefficient have a significant effect on small signal stability, transient response of the system and network losses. The trade-off associated with the network...

  9. Loss of phosphodiesterase 4D mediates acquired triapine resistance via Epac-Rap1-Integrin signaling.

    Science.gov (United States)

    Miklos, Walter; Heffeter, Petra; Pirker, Christine; Hager, Sonja; Kowol, Christian R; van Schoonhoven, Sushilla; Stojanovic, Mirjana; Keppler, Bernhard K; Berger, Walter

    2016-12-20

    Triapine, an anticancer thiosemicarbazone, is currently under clinical investigation. Whereas promising results were obtained in hematological diseases, trials in solid tumors widely failed. To understand mechanisms causing triapine insensitivity, we have analysed genomic alterations in a triapine-resistant SW480 subline (SW480/tria). Only one distinct genomic loss was observed specifically in SW480/tria cells affecting the phosphodiesterase 4D (PDE4D) gene locus. Accordingly, pharmacological inhibition of PDE4D resulted in significant triapine resistance in SW480 cells. Hence, we concluded that enhanced cyclic AMP levels might confer protection against triapine. Indeed, hyperactivation of both major downstream pathways, namely the protein kinase A (PKA)-cAMP response element-binding protein (Creb) and the exchange protein activated by cAMP (Epac)-Ras-related protein 1 (Rap1) signaling axes, was observed in SW480/tria cells. Unexpectedly, inhibition of PKA did not re-sensitize SW480/tria cells against triapine. In contrast, Epac activation resulted in distinct triapine resistance in SW480 cells. Conversely, knock-down of Epac expression and pharmacological inhibition of Rap1 re-sensitized SW480/tria cells against triapine. Rap1 is a well-known regulator of integrins. Accordingly, SW480/tria cells displayed enhanced plasma membrane expression of several integrin subunits, enhanced adhesion especially to RGD-containing matrix components, and bolstered activation/expression of the integrin downstream effectors Src and RhoA/Rac. Accordingly, integrin and Src inhibition resulted in potent triapine re-sensitization especially of SW480/tria cells. In summary, we describe for the first time integrin activation based on cAMP-Epac-Rap1 signaling as acquired drug resistance mechanism. combinations of triapine with inhibitors of several steps in this resistance cascade might be feasible strategies to overcome triapine insensitivity of solid tumors.

  10. Loss of claudin-3 expression induces IL6/gp130/Stat3 signaling to promote colon cancer malignancy by hyperactivating Wnt/β-catenin signaling.

    Science.gov (United States)

    Ahmad, R; Kumar, B; Chen, Z; Chen, X; Müller, D; Lele, S M; Washington, M K; Batra, S K; Dhawan, P; Singh, A B

    2017-11-23

    The hyperactivated Wnt/β-catenin signaling acts as a switch to induce epithelial to mesenchymal transition and promote colorectal cancer. However, due to its essential role in gut homeostasis, therapeutic targeting of this pathway has proven challenging. Additionally, IL-6/Stat-3 signaling, activated by microbial translocation through the dysregulated mucosal barrier in colon adenomas, facilitates the adenoma to adenocarcinomas transition. However, inter-dependence between these signaling pathways and key mucosal barrier components in regulating colon tumorigenesis and cancer progression remains unclear. In current study, we have discovered, using a comprehensive investigative regimen, a novel and tissue-specific role of claudin-3, a tight junction integral protein, in inhibiting colon cancer progression by serving as the common rheostat of Stat-3 and Wnt-signaling activation. Loss of claudin-3 also predicted poor patient survival. These findings however contrasted an upregulated claudin-3 expression in other cancer types and implicated role of the epigenetic regulation. Claudin-3-/- mice revealed dedifferentiated and leaky colonic epithelium, and developed invasive adenocarcinoma when subjected to colon cancer. Wnt-signaling hyperactivation, albeit in GSK-3β independent manner, differentiated colon cancer in claudin-3-/- mice versus WT-mice. Claudin-3 loss also upregulated the gp130/IL6/Stat3 signaling in colonic epithelium potentially assisted by infiltrating immune components. Genetic and pharmacological studies confirmed that claudin-3 loss induces Wnt/β-catenin activation, which is further exacerbated by Stat-3-activation and help promote colon cancer. Overall, these novel findings identify claudin-3 as a therapeutic target for inhibiting overactivation of Wnt-signaling to prevent CRC malignancy.

  11. Loss of Signal: Aeromedical Lessons Learned from the STS-107 Columbia Space Shuttle Mishap

    Science.gov (United States)

    Stepaniak, Philip C. (Editor); Lane, Helen W. (Editor); Davis, Jeffrey R.

    2014-01-01

    The editors of Loss of Signal wanted to document the aeromedical lessons learned from the Space Shuttle Columbia mishap. The book is intended to be an accurate and easily understood account of the entire process of recovering and analyzing the human remains, investigating and analyzing what happened to the crew, and using the resulting information to recommend ways to prevent mishaps and provide better protection to crewmembers. Our goal is to capture the passions of those who devoted their energies in responding to the Columbia mishap. We have reunited authors who were directly involved in each of these aspects. These authors tell the story of their efforts related to the Columbia mishap from their point of view. They give the reader an honest description of their responsibilities and share their challenges, their experiences, and their lessons learned on how to enhance crew safety and survival, and how to be prepared to support space mishap investigations. As a result of this approach, a few of the chapters have some redundancy of information and authors' opinions may differ. In no way did we or they intend to assign blame or criticize anyone's professional efforts. All those involved did their best to obtain the truth in the situations to which they were assigned.

  12. Loss of a conserved tRNA anticodon modification perturbs cellular signaling.

    Directory of Open Access Journals (Sweden)

    Boris Zinshteyn

    Full Text Available Transfer RNA (tRNA modifications enhance the efficiency, specificity and fidelity of translation in all organisms. The anticodon modification mcm(5s(2U(34 is required for normal growth and stress resistance in yeast; mutants lacking this modification have numerous phenotypes. Mutations in the homologous human genes are linked to neurological disease. The yeast phenotypes can be ameliorated by overexpression of specific tRNAs, suggesting that the modifications are necessary for efficient translation of specific codons. We determined the in vivo ribosome distributions at single codon resolution in yeast strains lacking mcm(5s(2U. We found accumulations at AAA, CAA, and GAA codons, suggesting that translation is slow when these codons are in the ribosomal A site, but these changes appeared too small to affect protein output. Instead, we observed activation of the GCN4-mediated stress response by a non-canonical pathway. Thus, loss of mcm(5s(2U causes global effects on gene expression due to perturbation of cellular signaling.

  13. Loss of TGF-β Adaptor β2SP Activates Notch Signaling and SOX9 Expression in Esophageal Adenocarcinoma

    Science.gov (United States)

    Song, Shumei; Maru, Dipen M.; Ajani, Jaffer A.; Chan, Chia-Hsin; Honjo, Soichiro; Lin, Hui-Kuan; Correa, Arlene; Hofstetter, Wayne L.; Davila, Marta; Stroehlein, John; Mishra, Lopa

    2013-01-01

    TGF-β and Notch signaling pathways play important roles in regulating self-renewal of stem cells and gastrointestinal carcinogenesis. Loss of TGF-β signaling components activates Notch signaling in esophageal adenocarcinoma, but the basis for this effect has been unclear. Here we report that loss of TGF-β adapter β2SP (SPNB2) activates Notch signaling and its target SOX9 in primary fibroblasts or esophageal adenocarcinoma cells. Expression of the stem cell marker SOX9 was markedly higher in esophageal adenocarcinoma tumor tissues than normal tissues, and its higher nuclear staining in tumors correlated with poorer survival and lymph node invasion in esophageal adenocarcinoma patients. Downregulation of β2SP by lentivirus short hairpin RNA increased SOX9 transcription and expression, enhancing nuclear localization for both active Notch1 (intracellular Notch1, ICN1) and SOX9. In contrast, reintroduction into esophageal adenocarcinoma cells of β2SP and a dominant-negative mutant of the Notch coactivator mastermind-like (dnMAN) decreased SOX9 promoter activity. Tumor sphere formation and invasive capacity in vitro and tumor growth in vivo were increased in β2SP-silenced esophageal adenocarcinoma cells. Conversely, SOX9 silencing rescued the phenotype of esophageal adenocarcinoma cells with loss of β2SP. Interaction between Smad3 and ICN1 via Smad3 MH1 domain was also observed, with loss of β2SP increasing the binding between these proteins, inducing expression of Notch targets SOX9 and C-MYC, and decreasing expression of TGF-β targets p21(CDKN1A), p27 (CDKN1B), and E-cadherin. Taken together, our findings suggest that loss of β2SP switches TGF-β signaling from tumor suppression to tumor promotion by engaging Notch signaling and activating SOX9. PMID:23536563

  14. Loss of the alpha7 integrin promotes extracellular signal-regulated kinase activation and altered vascular remodeling.

    Science.gov (United States)

    Welser, Jennifer V; Lange, Naomi; Singer, Cherie A; Elorza, Margaret; Scowen, Paul; Keef, Kathleen D; Gerthoffer, William T; Burkin, Dean J

    2007-09-28

    Vascular smooth muscle cell (VSMC) proliferation and migration are underlying factors in the development and progression of cardiovascular disease. Studies have shown that altered expression of vascular integrins and extracellular matrix proteins may contribute to the vascular remodeling observed after arterial injury and during disease. We have recently shown that loss of the alpha7beta1 integrin results in VSMC hyperplasia. To investigate the cellular mechanisms underlying this phenotype, we have examined changes in cell signaling pathways associated with VSMC proliferation. Several studies have demonstrated the mitogen-activated protein kinase signaling pathway is activated in response to vascular injury and disease. In this study, we show that loss of the alpha7 integrin in VSMCs results in activation of the extracellular signal-regulated kinase and translocation of the activated kinase to the nucleus. Forced expression of the alpha7 integrin or use of the mitogen-activated protein kinase kinase 1 inhibitor U0126 in alpha7 integrin-deficient VSMCs suppressed extracellular signal-regulated kinase activation and restored the differentiated phenotype to alpha7 integrin-null cells in a manner dependent on Ras signaling. Alpha7 integrin-null mice displayed profound vascular remodeling in response to injury with pronounced neointimal formation and reduced vascular compliance. These findings demonstrate that the alpha7beta1 integrin negatively regulates extracellular signal-regulated kinase activation and suggests an important role for this integrin as part of a signaling complex regulating VSMC phenotype switching.

  15. Effect of extreme data loss on long-range correlated and anti-correlated signals quantified by detrended fluctuation analysis

    CERN Document Server

    Ma, Qianli D Y; Bernaola-Galván, Pedro; Yoneyama, Mitsuru; Ivanov, Plamen Ch

    2010-01-01

    We investigate how extreme loss of data affects the scaling behavior of long-range power-law correlated and anti-correlated signals applying the DFA method. We introduce a segmentation approach to generate surrogate signals by randomly removing data segments from stationary signals with different types of correlations. These surrogate signals are characterized by: (i) the DFA scaling exponent $\\alpha$ of the original correlated signal, (ii) the percentage $p$ of the data removed, (iii) the average length $\\mu$ of the removed (or remaining) data segments, and (iv) the functional form of the distribution of the length of the removed (or remaining) data segments. We find that the {\\it global} scaling exponent of positively correlated signals remains practically unchanged even for extreme data loss of up to 90%. In contrast, the global scaling of anti-correlated signals changes to uncorrelated behavior even when a very small fraction of the data is lost. These observations are confirmed on the examples of human g...

  16. Transient Oxygen/Glucose Deprivation Causes a Delayed Loss of Mitochondria and Increases Spontaneous Calcium Signaling in Astrocytic Processes.

    Science.gov (United States)

    O'Donnell, John C; Jackson, Joshua G; Robinson, Michael B

    2016-07-06

    Recently, mitochondria have been localized to astrocytic processes where they shape Ca(2+) signaling; this relationship has not been examined in models of ischemia/reperfusion. We biolistically transfected astrocytes in rat hippocampal slice cultures to facilitate fluorescent confocal microscopy, and subjected these slices to transient oxygen/glucose deprivation (OGD) that causes delayed excitotoxic death of CA1 pyramidal neurons. This insult caused a delayed loss of mitochondria from astrocytic processes and increased colocalization of mitochondria with the autophagosome marker LC3B. The losses of neurons in area CA1 and mitochondria in astrocytic processes were blocked by ionotropic glutamate receptor (iGluR) antagonists, tetrodotoxin, ziconotide (Ca(2+) channel blocker), two inhibitors of reversed Na(+)/Ca(2+) exchange (KB-R7943, YM-244769), or two inhibitors of calcineurin (cyclosporin-A, FK506). The effects of OGD were mimicked by NMDA. The glutamate uptake inhibitor (3S)-3-[[3-[[4-(trifluoromethyl)benzoyl]amino]phenyl]methoxy]-l-aspartate increased neuronal loss after OGD or NMDA, and blocked the loss of astrocytic mitochondria. Exogenous glutamate in the presence of iGluR antagonists caused a loss of mitochondria without a decrease in neurons in area CA1. Using the genetic Ca(2+) indicator Lck-GCaMP-6S, we observed two types of Ca(2+) signals: (1) in the cytoplasm surrounding mitochondria (mitochondrially centered) and (2) traversing the space between mitochondria (extramitochondrial). The spatial spread, kinetics, and frequency of these events were different. The amplitude of both types was doubled and the spread of both types changed by ∼2-fold 24 h after OGD. Together, these data suggest that pathologic activation of glutamate transport and increased astrocytic Ca(2+) through reversed Na(+)/Ca(2+) exchange triggers mitochondrial loss and dramatic increases in Ca(2+) signaling in astrocytic processes. Astrocytes, the most abundant cell type in the brain

  17. High Levels of Canonical Wnt Signaling Lead to Loss of Stemness and Increased Differentiation in Hematopoietic Stem Cells

    Directory of Open Access Journals (Sweden)

    Farbod Famili

    2016-05-01

    Full Text Available Canonical Wnt signaling regulates the self-renewal of most if not all stem cell systems. In the blood system, the role of Wnt signaling has been the subject of much debate but there is consensus that high Wnt signals lead to loss of reconstituting capacity. To better understand this phenomenon, we have taken advantage of a series of hypomorphic mutant Apc alleles resulting in a broad range of Wnt dosages in hematopoietic stem cells (HSCs and performed whole-genome gene expression analyses. Gene expression profiling and functional studies show that HSCs with APC mutations lead to high Wnt levels, enhanced differentiation, and diminished proliferation but have no effect on apoptosis, collectively leading to loss of stemness. Thus, we provide mechanistic insight into the role of APC mutations and Wnt signaling in HSC biology. As Wnt signals are explored in various in vivo and ex vivo expansion protocols for HSCs, our findings also have clinical ramifications.

  18. Automatic Frequency Identification under Sample Loss in Sinusoidal Pulse Width Modulation Signals Using an Iterative Autocorrelation Algorithm

    Directory of Open Access Journals (Sweden)

    Alejandro Said

    2016-08-01

    Full Text Available In this work, we present a simple algorithm to calculate automatically the Fourier spectrum of a Sinusoidal Pulse Width Modulation Signal (SPWM. Modulated voltage signals of this kind are used in industry by speed drives to vary the speed of alternating current motors while maintaining a smooth torque. Nevertheless, the SPWM technique produces undesired harmonics, which yield stator heating and power losses. By monitoring these signals without human interaction, it is possible to identify the harmonic content of SPWM signals in a fast and continuous manner. The algorithm is based in the autocorrelation function, commonly used in radar and voice signal processing. Taking advantage of the symmetry properties of the autocorrelation, the algorithm is capable of estimating half of the period of the fundamental frequency; thus, allowing one to estimate the necessary number of samples to produce an accurate Fourier spectrum. To deal with the loss of samples, i.e., the scan backlog, the algorithm iteratively acquires and trims the discrete sequence of samples until the required number of samples reaches a stable value. The simulation shows that the algorithm is not affected by either the magnitude of the switching pulses or the acquisition noise.

  19. The impact of spin coupling signal loss on fat content characterization in multi-echo acquisitions with different echo spacing.

    Science.gov (United States)

    Nikiforaki, K; Manikis, G C; Boursianis, T; Marias, K; Karantanas, A; Maris, T G

    2017-05-01

    This study aimed to assess the effect of echo spacing in transverse magnetization (T2) signal decay of gel and fat (oil) samples. Additionally, we assess the feasibility of using spin coupling as a determinant of fat content. Phantoms of known T2 values, as well as vegetable oil phantoms, were scanned at 1.5T scanner with a multi echo FSE sequence of variable echo spacing above and below the empirical threshold of 20ms for echo train signal modulation (6.7, 13.6, 26.8, and 40ms). T2 values were calculated from monoexponential fitting of the data. Relative signal loss between the four acquisitions of different echo spacing was calculated. Agreement in the T2 values of water gel phantom was observed in all acquisitions as opposed to fat phantom (oil) samples. Relative differences in signal intensity between two successive sequences of different echo spacing on composite fat/water regions of interest was found to be linearly correlated to fat fraction of the ROI. The sample specific degree of signal loss that was observed between different fat samples (vegetable oils) can be attributed to the composition of each sample in J coupled fat components. Hence, spin coupling may be used as a determinant of fat content. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Loss of the tumor suppressor gene NF2, encoding merlin, constitutively activates integrin-dependent mTORC1 signaling.

    Science.gov (United States)

    López-Lago, Miguel A; Okada, Tomoyo; Murillo, Miguel M; Socci, Nick; Giancotti, Filippo G

    2009-08-01

    Integrin signaling promotes, through p21-activated kinase, phosphorylation and inactivation of the tumor suppressor merlin, thus removing a block to mitogenesis in normal cells. However, the biochemical function of merlin and the effector pathways critical for the pathogenesis of malignant mesothelioma and other NF2-related malignancies are not known. We report that integrin-specific signaling promotes activation of mTORC1 and cap-dependent mRNA translation. Depletion of merlin rescues mTORC1 signaling in cells deprived of anchorage to a permissive extracellular matrix, suggesting that integrin signaling controls mTORC1 through inactivation of merlin. This signaling pathway controls translation of the cyclin D1 mRNA and, thereby, cell cycle progression. In addition, it promotes cell survival. Analysis of a panel of malignant mesothelioma cell lines reveals a strong correlation between loss of merlin and activation of mTORC1. Merlin-negative lines are sensitive to the growth-inhibitory effect of rapamycin, and the expression of recombinant merlin renders them partially resistant to rapamycin. Conversely, depletion of merlin restores rapamycin sensitivity in merlin-positive lines. These results indicate that integrin-mediated adhesion promotes mTORC1 signaling through the inactivation of merlin. Furthermore, they reveal that merlin-negative mesotheliomas display unregulated mTORC1 signaling and are sensitive to rapamycin, thus providing a preclinical rationale for prospective, biomarker-driven clinical studies of mTORC1 inhibitors in these tumors.

  1. Signaling proteins that influence energy intake may affect unintentional weight loss in elderly persons.

    Science.gov (United States)

    Wernette, Catherine M; White, B Douglas; Zizza, Claire A

    2011-06-01

    After age 70 to 75 years, average body weight decreases both in ailing and healthy people because of a loss of appetite that results in reduced energy intake and the loss of body fat and lean muscle tissue. This so-called anorexia of aging predisposes elderly people to continued pathologic weight loss and malnutrition-major causes of morbidity and mortality. Health care professionals must understand the many factors involved in the anorexia of aging to help older adults prevent unintentional weight loss. Psychological, social, and cultural factors are important effectors; however, physiological factors are emphasized here because they are not thoroughly understood and they make it inherently difficult for most people to alter their body weight. Monoamines, steroid hormones (glucocorticoids and mineralocorticoids), endocannabinoids, and proteins all influence body weight. This review is an analysis of proteins from the brain, pancreas, adipose tissue, and gastrointestinal tract that are known to affect energy intake and energy balance, with an attempt to identify those factors that may change with aging. The articles included in this review were obtained by a PubMed database search using the keywords mouse OR rat OR human AND aged OR aging OR older OR elderly AND adult AND anorexia OR "unintentional weight loss," and each of the individual proteins discussed, as well as from the reference lists of those articles. The results reveal that some proteins may be important in the development of unintentional weight loss in elderly persons, whereas others may not have a significant role. However, many of the proteins that could conceivably have a role in unintentional weight loss have not yet been studied with that question in mind. Preventing unintentional weight loss in older adults is an important goal and further research on the role of proteins important for the maintenance of energy balance and the development of unintentional weight loss in elderly persons is

  2. Effects of sensorineural hearing loss on temporal coding of narrowband and broadband signals in the auditory periphery.

    Science.gov (United States)

    Henry, Kenneth S; Heinz, Michael G

    2013-09-01

    People with sensorineural hearing loss have substantial difficulty understanding speech under degraded listening conditions. Behavioral studies suggest that this difficulty may be caused by changes in auditory processing of the rapidly-varying temporal fine structure (TFS) of acoustic signals. In this paper, we review the presently known effects of sensorineural hearing loss on processing of TFS and slower envelope modulations in the peripheral auditory system of mammals. Cochlear damage has relatively subtle effects on phase locking by auditory-nerve fibers to the temporal structure of narrowband signals under quiet conditions. In background noise, however, sensorineural loss does substantially reduce phase locking to the TFS of pure-tone stimuli. For auditory processing of broadband stimuli, sensorineural hearing loss has been shown to severely alter the neural representation of temporal information along the tonotopic axis of the cochlea. Notably, auditory-nerve fibers innervating the high-frequency part of the cochlea grow increasingly responsive to low-frequency TFS information and less responsive to temporal information near their characteristic frequency (CF). Cochlear damage also increases the correlation of the response to TFS across fibers of varying CF, decreases the traveling-wave delay between TFS responses of fibers with different CFs, and can increase the range of temporal modulation frequencies encoded in the periphery for broadband sounds. Weaker neural coding of temporal structure in background noise and degraded coding of broadband signals along the tonotopic axis of the cochlea are expected to contribute considerably to speech perception problems in people with sensorineural hearing loss. This article is part of a Special Issue entitled "Annual Reviews 2013". Copyright © 2013 Elsevier B.V. All rights reserved.

  3. Effect of significant data loss on identifying electric signals that precede rupture estimated by detrended fluctuation analysis in natural time.

    Science.gov (United States)

    Skordas, E S; Sarlis, N V; Varotsos, P A

    2010-09-01

    Electric field variations that appear before rupture have been recently studied by employing the detrended fluctuation analysis (DFA) to quantify their long-range temporal correlations. These studies revealed that seismic electric signal (SES) activities exhibit a scale invariant feature with an exponent αDFA≈1 over all scales investigated (around five orders of magnitude). Here, we study what happens upon significant data loss, which is a question of primary practical importance, and show that the DFA applied to the natural time representation of the remaining data still reveals for SES activities an exponent close to 1.0, which markedly exceeds the exponent found in artificial (man-made) noises. This enables the identification of a SES activity with probability of 75% even after a significant (70%) data loss. The probability increases to 90% or larger for 50% data loss.

  4. Catalase-dependent H2O2 consumption by cardiac mitochondria and redox-mediated loss in insulin signaling.

    Science.gov (United States)

    Rindler, Paul M; Cacciola, Angela; Kinter, Michael; Szweda, Luke I

    2016-11-01

    We have recently demonstrated that catalase content in mouse cardiac mitochondria is selectively elevated in response to high dietary fat, a nutritional state associated with oxidative stress and loss in insulin signaling. Catalase and various isoforms of glutathione peroxidase and peroxiredoxin each catalyze the consumption of H2O2 Catalase, located primarily within peroxisomes and to a lesser extent mitochondria, has a low binding affinity for H2O2 relative to glutathione peroxidase and peroxiredoxin. As such, the contribution of catalase to mitochondrial H2O2 consumption is not well understood. In the current study, using highly purified cardiac mitochondria challenged with micromolar concentrations of H2O2, we found that catalase contributes significantly to mitochondrial H2O2 consumption. In addition, catalase is solely responsible for removal of H2O2 in nonrespiring or structurally disrupted mitochondria. Finally, in mice fed a high-fat diet, mitochondrial-derived H2O2 is responsible for diminished insulin signaling in the heart as evidenced by reduced insulin-stimulated Akt phosphorylation. While elevated mitochondrial catalase content (∼50%) enhanced the capacity of mitochondria to consume H2O2 in response to high dietary fat, the selective increase in catalase did not prevent H2O2-induced loss in cardiac insulin signaling. Taken together, our results indicate that mitochondrial catalase likely functions to preclude the formation of high levels of H2O2 without perturbing redox-dependent signaling. Copyright © 2016 the American Physiological Society.

  5. DKK1 mediated inhibition of Wnt signaling in postnatal mice leads to loss of TEC progenitors and thymic degeneration.

    Directory of Open Access Journals (Sweden)

    Masako Osada

    2010-02-01

    Full Text Available Thymic epithelial cell (TEC microenvironments are essential for the recruitment of T cell precursors from the bone marrow, as well as the subsequent expansion and selection of thymocytes resulting in a mature self-tolerant T cell repertoire. The molecular mechanisms, which control both the initial development and subsequent maintenance of these critical microenvironments, are poorly defined. Wnt signaling has been shown to be important to the development of several epithelial tissues and organs. Regulation of Wnt signaling has also been shown to impact both early thymocyte and thymic epithelial development. However, early blocks in thymic organogenesis or death of the mice have prevented analysis of a role of canonical Wnt signaling in the maintenance of TECs in the postnatal thymus.Here we demonstrate that tetracycline-regulated expression of the canonical Wnt inhibitor DKK1 in TECs localized in both the cortex and medulla of adult mice, results in rapid thymic degeneration characterized by a loss of DeltaNP63(+ Foxn1(+ and Aire(+ TECs, loss of K5K8DP TECs thought to represent or contain an immature TEC progenitor, decreased TEC proliferation and the development of cystic structures, similar to an aged thymus. Removal of DKK1 from DKK1-involuted mice results in full recovery, suggesting that canonical Wnt signaling is required for the differentiation or proliferation of TEC populations needed for maintenance of properly organized adult thymic epithelial microenvironments.Taken together, the results of this study demonstrate that canonical Wnt signaling within TECs is required for the maintenance of epithelial microenvironments in the postnatal thymus, possibly through effects on TEC progenitor/stem cell populations. Downstream targets of Wnt signaling, which are responsible for maintenance of these TEC progenitors may provide useful targets for therapies aimed at counteracting age associated thymic involution or the premature thymic

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

    Science.gov (United States)

    Muñoz-Bravo, Jose Luis; Flores-Martínez, Alvaro; 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.

  7. Loss of emerin alters myogenic signaling and miRNA expression in mouse myogenic progenitors.

    Directory of Open Access Journals (Sweden)

    Adam J Koch

    Full Text Available Emerin is an integral membrane protein of the inner nuclear membrane. Mutations in emerin cause X-linked Emery-Dreifuss muscular dystrophy (EDMD, a disease characterized by skeletal muscle wasting and dilated cardiomyopathy. Current evidence suggests the muscle wasting phenotype of EDMD is caused by defective myogenic progenitor cell differentiation and impaired muscle regeneration. We obtained genome-wide expression data for both mRNA and micro-RNA (miRNA in wildtype and emerin-null mouse myogenic progenitor cells. We report here that emerin-null myogenic progenitors exhibit differential expression of multiple signaling pathway components required for normal muscle development and regeneration. Components of the Wnt, IGF-1, TGF-β, and Notch signaling pathways are misexpressed in emerin-null myogenic progenitors at both the mRNA and protein levels. We also report significant perturbations in the expression and activation of p38/Mapk14 in emerin-null myogenic progenitors, showing that perturbed expression of Wnt, IGF-1, TGF-β, and Notch signaling components disrupts normal downstream myogenic signaling in these cells. Collectively, these data support the hypothesis that emerin is essential for proper myogenic signaling in myogenic progenitors, which is necessary for myogenic differentiation and muscle regeneration.

  8. 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

  9. Gain and loss of polyadenylation signals during evolution of green algae

    Directory of Open Access Journals (Sweden)

    Glöckner Gernot

    2007-04-01

    Full Text Available Abstract Background The Viridiplantae (green algae and land plants consist of two monophyletic lineages: the Chlorophyta and the Streptophyta. Most green algae belong to the Chlorophyta, while the Streptophyta include all land plants and a small group of freshwater algae known as Charophyceae. Eukaryotes attach a poly-A tail to the 3' ends of most nuclear-encoded mRNAs. In embryophytes, animals and fungi, the signal for polyadenylation contains an A-rich sequence (often AAUAAA or related sequence 13 to 30 nucleotides upstream from the cleavage site, which is commonly referred to as the near upstream element (NUE. However, it has been reported that the pentanucleotide UGUAA is used as polyadenylation signal for some genes in volvocalean algae. Results We set out to investigate polyadenylation signal differences between streptophytes and chlorophytes that may have emerged shortly after the evolutionary split between Streptophyta and Chlorophyta. We therefore analyzed expressed genes (ESTs from three streptophyte algae, Mesostigma viride, Klebsormidium subtile and Coleochaete scutata, and from two early-branching chlorophytes, Pyramimonas parkeae and Scherffelia dubia. In addition, to extend the database, our analyses included ESTs from six other chlorophytes (Acetabularia acetabulum, Chlamydomonas reinhardtii, Helicosporidium sp. ex Simulium jonesii, Prototheca wickerhamii, Scenedesmus obliquus and Ulva linza and one streptophyte (Closterium peracerosum. Our results indicate that polyadenylation signals in green algae vary widely. The UGUAA motif is confined to late-branching Chlorophyta. Most streptophyte algae do not have an A-rich sequence motif like that in embryophytes, animals and fungi. We observed polyadenylation signals similar to those of Arabidopsis and other land plants only in Mesostigma. Conclusion Polyadenylation signals in green algae show considerable variation. A new NUE (UGUAA was invented in derived chlorophytes and replaced

  10. Wavelength conversion of QAM signals in a low loss CMOS compatible spiral waveguide

    DEFF Research Database (Denmark)

    Da Ros, Francesco; Porto da Silva, Edson; Zibar, Darko

    2017-01-01

    We demonstrate wavelength conversion of quadrature amplitude modulation (QAM) signals, including 32-GBd quadrature phase-shift keying and 10-GBd 16-QAM, in a 50-cm long high index doped glass spiral waveguide. The quality of the generated idlers for up to 20 nm of wavelength shift is sufficient...

  11. Loss of C9orf72 Enhances Autophagic Activity via Deregulated mTOR and TFEB Signaling.

    Directory of Open Access Journals (Sweden)

    Janet Ugolino

    2016-11-01

    Full Text Available The most common cause of the neurodegenerative diseases amyotrophic lateral sclerosis and frontotemporal dementia is a hexanucleotide repeat expansion in C9orf72. Here we report a study of the C9orf72 protein by examining the consequences of loss of C9orf72 functions. Deletion of one or both alleles of the C9orf72 gene in mice causes age-dependent lethality phenotypes. We demonstrate that C9orf72 regulates nutrient sensing as the loss of C9orf72 decreases phosphorylation of the mTOR substrate S6K1. The transcription factor EB (TFEB, a master regulator of lysosomal and autophagy genes, which is negatively regulated by mTOR, is substantially up-regulated in C9orf72 loss-of-function animal and cellular models. Consistent with reduced mTOR activity and increased TFEB levels, loss of C9orf72 enhances autophagic flux, suggesting that C9orf72 is a negative regulator of autophagy. We identified a protein complex consisting of C9orf72 and SMCR8, both of which are homologous to DENN-like proteins. The depletion of C9orf72 or SMCR8 leads to significant down-regulation of each other's protein level. Loss of SMCR8 alters mTOR signaling and autophagy. These results demonstrate that the C9orf72-SMCR8 protein complex functions in the regulation of metabolism and provide evidence that loss of C9orf72 function may contribute to the pathogenesis of relevant diseases.

  12. Exercise associated hormonal signals as powerful determinants of an effective fat mass loss.

    Science.gov (United States)

    Bajer, B; Vlcek, M; Galusova, A; Imrich, R; Penesova, A

    2015-07-01

    Obesity management for achieving an effective weight loss includes dietary modification and exercise [resistance (strength), endurance (cardiovascular) or intervals training (high-intensity intermittent exercise)]. Regular exercise acutely increases fat oxidation, which induces loss of fat mass and increases energy expenditure. Moreover, it has a positive effect on the physical (improved insulin sensitivity, lipid profile, etc.) and mental health (mood, cognition, memory, sleep, etc.). Endocrine responses to muscle actions are affected by many factors, including the exercise muscle groups (lower and upper body), load/volume, time-under tension, and rest-period intervals between sets, training status, gender, and age. The aim of this review is to summarize, evaluate, and clarify the literature data focusing on the endocrine responses to different types of exercise, including the frequency, intensity, and type of movement with regard to the fat loss strategies. Many studies have investigated anabolic [growth hormone, insulin-like growth factor-1 (IGF-1), testosterone] and gluco- and appetite- regulatory (insulin, cortisol, ghrelin) hormone responses and adaptations of skeletal muscles to exercise. Muscle tissue is a critical endocrine organ, playing important role in the regulation of several physiological and metabolic events. Moreover, we are also describing the response of some other substances to exercise, such as myokines [irisin, apelin, brain-derived neurotrophic factor (BDNF), myostatin, and fibroblast growth factor 21 (FGF21)]. It is proposed that reducing intra-abdominal fat mass and increasing cardiorespiratory fitness through improving nutritional quality, reducing sedentary behavior, and increase the participation in physical activity/exercise, might be associated with clinical benefits, sometimes even in the absence of weight loss.

  13. Distinct effects of loss of classical estrogen receptor signaling versus complete deletion of estrogen receptor alpha on bone.

    Science.gov (United States)

    Syed, Farhan A; Fraser, Daniel G; Monroe, David G; Khosla, Sundeep

    2011-08-01

    Estrogen receptor (ER) α is a major regulator of bone metabolism which can modulate gene expression via a "classical" pathway involving direct DNA binding to estrogen-response elements (EREs) or via "non-classical" pathways involving protein-protein interactions. While the skeletal consequences of loss of ERE binding by ERα have been described, a significant unresolved question is how loss of ERE binding differs from complete loss of ERα. Thus, we compared the skeletal phenotype of wild-type (ERα(+/+)) and ERα knock out (ERα(-/-)) mice with that of mice in which the only ERα present had a knock-in mutation abolishing ERE binding (non-classical ERα knock-in [NERKI], ERα(-/NERKI)). All three groups were in the same genetic background (C57BL/6). As compared to both ERα(+/+) and ERα(-/-) mice, ERα(-/NERKI) mice had significantly reduced cortical volumetric bone mineral density and thickness at the tibial diaphysis; this was accompanied by significant decreases in periosteal and endocortical mineral apposition rates. Colony forming unit (CFU)-fibroblast, CFU-alkaline phosphatase, and CFU-osteoblast numbers were all increased in ERα(-/-) compared to ERα(+/+) mice, but reduced in ERα(-/NERKI) mice compared to the two other groups. Thus, using mice in identical genetic backgrounds, our data indicate that the presence of an ERα that cannot bind DNA but can function through protein-protein interactions may have more deleterious skeletal effects than complete loss of ERα. These findings suggest that shifting the balance of classical versus non-classical ERα signaling triggers pathways that impair bone formation. Further studies defining these pathways may lead to novel approaches to selectively modulate ER signaling for beneficial skeletal effects. Copyright © 2011 Elsevier Inc. All rights reserved.

  14. Loss of guanylyl cyclase C (GCC signaling leads to dysfunctional intestinal barrier.

    Directory of Open Access Journals (Sweden)

    Xiaonan Han

    2011-01-01

    Full Text Available Guanylyl Cyclase C (GCC signaling via uroguanylin (UGN and guanylin activation is a critical mediator of intestinal fluid homeostasis, intestinal cell proliferation/apoptosis, and tumorigenesis. As a mechanism for some of these effects, we hypothesized that GCC signaling mediates regulation of intestinal barrier function.Paracellular permeability of intestinal segments was assessed in wild type (WT and GCC deficient (GCC-/- mice with and without lipopolysaccharide (LPS challenge, as well as in UGN deficient (UGN-/- mice. IFNγ and myosin light chain kinase (MLCK levels were determined by real time PCR. Expression of tight junction proteins (TJPs, phosphorylation of myosin II regulatory light chain (MLC, and STAT1 activation were examined in intestinal epithelial cells (IECs and intestinal mucosa. The permeability of Caco-2 and HT-29 IEC monolayers, grown on Transwell filters was determined in the absence and presence of GCC RNA interference (RNAi. We found that intestinal permeability was increased in GCC-/- and UGN-/- mice compared to WT, accompanied by increased IFNγ levels, MLCK and STAT1 activation in IECs. LPS challenge promotes greater IFNγ and STAT1 activation in IECs of GCC-/- mice compared to WT mice. Claudin-2 and JAM-A expression were reduced in GCC deficient intestine; the level of phosphorylated MLC in IECs was significantly increased in GCC-/- and UGN-/- mice compared to WT. GCC knockdown induced MLC phosphorylation, increased permeability in IEC monolayers under basal conditions, and enhanced TNFα and IFNγ-induced monolayer hyperpermeability.GCC signaling plays a protective role in the integrity of the intestinal mucosal barrier by regulating MLCK activation and TJ disassembly. GCC signaling activation may therefore represent a novel mechanism in maintaining the small bowel barrier in response to injury.

  15. Superoxide Dismutase 1 Loss Disturbs Intracellular Redox Signaling, Resulting in Global Age-Related Pathological Changes

    Directory of Open Access Journals (Sweden)

    Kenji Watanabe

    2014-01-01

    Full Text Available Aging is characterized by increased oxidative stress, chronic inflammation, and organ dysfunction, which occur in a progressive and irreversible manner. Superoxide dismutase (SOD serves as a major antioxidant and neutralizes superoxide radicals throughout the body. In vivo studies have demonstrated that copper/zinc superoxide dismutase-deficient (Sod1−/− mice show various aging-like pathologies, accompanied by augmentation of oxidative damage in organs. We found that antioxidant treatment significantly attenuated the age-related tissue changes and oxidative damage-associated p53 upregulation in Sod1−/− mice. This review will focus on various age-related pathologies caused by the loss of Sod1 and will discuss the molecular mechanisms underlying the pathogenesis in Sod1−/− mice.

  16. β2-Adrenergic signal transduction plays a detrimental role in subchondral bone loss of temporomandibular joint in osteoarthritis.

    Science.gov (United States)

    Jiao, Kai; Niu, Li-Na; Li, Qi-hong; Ren, Gao-tong; Zhao, Chang-ming; Liu, Yun-dong; Tay, Franklin R; Wang, Mei-qing

    2015-07-29

    The present study tested whether activation of the sympathetic tone by aberrant joint loading elicits abnormal subchondral bone remodeling in temporomandibular joint (TMJ) osteoarthritis. Abnormal dental occlusion was created in experimental rats, which were then intraperitoneally injected by saline, propranolol or isoproterenol. The norepinephrine contents, distribution of sympathetic nerve fibers, expression of β-adrenergic receptors (β-ARs) and remodeling parameters in the condylar subchondral bone were investigated. Mesenchymal stem cells (MSCs) from condylar subchondral bones were harvested for comparison of their β-ARs, pro-osteoclastic gene expressions and pro-osteoclastic function. Increases in norepinephrine level, sympathetic nerve fiber distribution and β2-AR expression were observed in the condylar subchondral bone of experimental rats, together with subchondral bone loss and increased osteoclast activity. β-antagonist (propranolol) suppressed subchondral bone loss and osteoclast hyperfunction while β-agonist (isoproterenol) exacerbated those responses. MSCs from experimental condylar subchondral bone expressed higher levels of β2-AR and RANKL; norepinephrine stimulation further increased their RANKL expression and pro-osteoclastic function. These effects were blocked by inhibition of β2-AR or the PKA pathway. RANKL expression by MSCs decreased after propranolol administration and increased after isoproterenol administration. It is concluded that β2-AR signal-mediated subchondral bone loss in TMJ osteoarthritisis associated with increased RANKL secretion by MSCs.

  17. Loss of Notch3 Signaling in Vascular Smooth Muscle Cells Promotes Severe Heart Failure Upon Hypertension.

    Science.gov (United States)

    Ragot, Hélène; Monfort, Astrid; Baudet, Mathilde; Azibani, Fériel; Fazal, Loubina; Merval, Régine; Polidano, Evelyne; Cohen-Solal, Alain; Delcayre, Claude; Vodovar, Nicolas; Chatziantoniou, Christos; Samuel, Jane-Lise

    2016-08-01

    Hypertension, which is a risk factor of heart failure, provokes adaptive changes at the vasculature and cardiac levels. Notch3 signaling plays an important role in resistance arteries by controlling the maturation of vascular smooth muscle cells. Notch3 deletion is protective in pulmonary hypertension while deleterious in arterial hypertension. Although this latter phenotype was attributed to renal and cardiac alterations, the underlying mechanisms remained unknown. To investigate the role of Notch3 signaling in the cardiac adaptation to hypertension, we used mice with either constitutive Notch3 or smooth muscle cell-specific conditional RBPJκ knockout. At baseline, both genotypes exhibited a cardiac arteriolar rarefaction associated with oxidative stress. In response to angiotensin II-induced hypertension, the heart of Notch3 knockout and SM-RBPJκ knockout mice did not adapt to pressure overload and developed heart failure, which could lead to an early and fatal acute decompensation of heart failure. This cardiac maladaptation was characterized by an absence of media hypertrophy of the media arteries, the transition of smooth muscle cells toward a synthetic phenotype, and an alteration of angiogenic pathways. A subset of mice exhibited an early fatal acute decompensated heart failure, in which the same alterations were observed, although in a more rapid timeframe. Altogether, these observations indicate that Notch3 plays a major role in coronary adaptation to pressure overload. These data also show that the hypertrophy of coronary arterial media on pressure overload is mandatory to initially maintain a normal cardiac function and is regulated by the Notch3/RBPJκ pathway. © 2016 American Heart Association, Inc.

  18. Comparison of Performance of Transcranial Contralateral Routing of Signal, Pre-Implanted Trimmer Digital and Digital Bone Anchored Hearing Aid in Adults with Unilateral Hearing Loss

    OpenAIRE

    Devi, Neelamegarajan; Chatni, Suma; Ramadevi, Kasetty Jagannathaiah S.; Fakruddin, Darga Baba

    2015-01-01

    Individuals with unilateral hearing loss of severe-profound degree face listening difficulties while localizing a sound source and while perceiving speech in the presence of noise. The objective was to compare the efficacy of the digitally programmable bone anchored hearing aid (BAHA), trimmer digital BAHA and the transcranial contralateral routing of signal (T-CROS) in improving the listening performance in adults with unilateral hearing loss. Twenty-four adults with unilateral hearing loss ...

  19. Attenuated Wnt/β-catenin signalling mediates methotrexate chemotherapy-induced bone loss and marrow adiposity in rats.

    Science.gov (United States)

    Georgiou, Kristen R; King, Tristan J; Scherer, Michaela A; Zhou, Hong; Foster, Bruce K; Xian, Cory J

    2012-06-01

    Cancer chemotherapy often causes significant bone loss, marrow adiposity and haematopoietic defects, yet the underlying mechanisms and recovery potential remain unclear. Wnt/β-catenin signalling is integral to the regulation of osteogenesis, adipogenesis and haematopoiesis; using a rat model, the current study investigated roles of this signalling pathway in changes to bone marrow stromal and haematopoietic cell differentiation after chemotherapy with methotrexate (MTX), a commonly used antimetabolite. MTX treatment in rats (5 daily administrations at 0.75 mg/kg) has previously been found to decrease bone volume and increase marrow fat, which was associated with increased osteoclastogenesis in haematopoietic cells and with an osteogenesis to adipogenesis switch in bone marrow stromal cells of treated rats. In the current study, on day 6 after the first MTX dose we found that accompanying these changes as well as a suppressed haematopoietic cellularity but increased granulocyte/macrophage differentiation potential, there was an increase in mRNA expression of Wnt antagonists sFRP-1 and Dkk-1 in bone, a reduction in nuclear β-catenin protein in bone marrow stromal cells, and decreased mRNA levels of β-catenin target genes lef-1, cyclin D1 and survivin, suggesting reduced activation of Wnt/β-catenin signalling in the bone during MTX-induced damage. Concurrent administration of BIO, a GSK-3β inhibitor that stabilises β-catenin, partially abrogated the MTX-induced transient changes in osteogenic/adipogenic commitment, granulocyte/macrophage lineage differentiation and osteoclast number. These findings demonstrate a potentially important role of Wnt/β-catenin signalling in MTX chemotherapy-induced cellular changes to the bone marrow microenvironment. Copyright © 2012 Elsevier Inc. All rights reserved.

  20. Signal intensity loss of the intervertebral discs in the cervical spine of young patients on fluid sensitive sequences

    Energy Technology Data Exchange (ETDEWEB)

    Bruin, F. de; Horst, S. ter; Bloem, J.L.; Reijnierse, M. [Leiden University Medical Center, Department of Radiology, C2-S, Albinusdreef 2, PO box 9600, Leiden (Netherlands); Berg, R. van den; Hooge, M. de; Gaalen, F. van; Heijde, D. van der [Leiden University Medical Center, Department of Rheumatology, Leiden (Netherlands); Fagerli, K.M. [Diakonhjemmet Hospital, Department of Rheumatology, Oslo (Norway); Landewe, R. [Amsterdam Medical Center, Department of Rheumatology, Amsterdam (Netherlands); Oosterhout, M. van [Groene Hartziekenhuis, Department of Rheumatology, Gouda (Netherlands)

    2016-03-15

    To evaluate the signal intensity (SI) of the intervertebral discs of the cervical spine on magnetic resonance (MR) fluid sensitive sequences, and correlate this to secondary signs of degeneration on MR and radiographs as well as to age. A total of 265 patients aged ≥16 with back pain (≥3-months, <2-year, onset <45-years) from the SPondyloArthritis Caught Early (SPACE) cohort were included. Sagittal 1.5 T MR images and lateral radiographs of the cervical spine were independently evaluated by two readers for: SI of the intervertebral discs using a grading system based of Pfirrmann (grade 1 normal/bright SI; 2 inhomogeneous/bright SI; 3 inhomogeneous/mildly decreased SI; 4 inhomogeneous/markedly decreased SI; 5 signal void), disc herniation and Modic changes (MRI) and disc space narrowing, osteophytes and sclerosis (radiograph). Readers were blinded for clinical information. Descriptive statistics were used for characteristics and prevalence of findings, and regression analysis was used for age and grades. Of 265 patients (36 % male, mean age 30), 221 (83 %) patients had 1 to 6 discs (median 4) with decreased SI. Of 1,590 discs, 737 (46 %) were grade 1; 711 (45 %) grade 2; 133 (8 %) grade 3; 8 (1 %) grade 4 and 1 (0 %) grade 5. Secondary signs of degeneration were rare and seen predominantly in C5-C7 and appear to be related to signal loss grade 3 and 4. Low signal intensity of intervertebral discs in absence of secondary degenerative signs in the cervical spine on fluid sensitive MR images might be pre-existing and part of the natural course. (orig.)

  1. Autoimmune pancreatitis results from loss of TGFbeta signalling in S100A4-positive dendritic cells.

    Science.gov (United States)

    Boomershine, C S; Chamberlain, A; Kendall, P; Afshar-Sharif, A-R; Huang, H; Washington, M K; Lawson, W E; Thomas, J W; Blackwell, T S; Bhowmick, N A

    2009-09-01

    Autoimmune pancreatitis (AIP) is a poorly understood human disease affecting the exocrine pancreas. The goal of the present study was to elucidate the pathogenic mechanisms underlying pancreatic autoimmunity in a murine disease model. A transgenic mouse with an S100A4/fibroblast-specific protein 1 (FSP1) Cre-mediated conditional knockout of the transforming growth factor beta (TGFbeta) type II receptor, termed Tgfbr2(fspKO), was used to determine the direct role of TGFbeta in S100A4(+) cells. Immunohistochemical studies suggested that Tgfbr2(fspKO) mice develop mouse AIP (mAIP) characterised by interlobular ductal inflammatory infiltrates and pancreatic autoantibody production. Fluorescence-activated cell sorting (FACS)-isolated dendritic cells (DCs) from diseased pancreata were verified to have S100A4-Cre-mediated DNA recombination. The Tgfbr2(fspKO) mice spontaneously developed mAIP by 6 weeks of age. DCs were confirmed to express S100A4, a previously reported protein expressed by fibroblasts. Adoptive transfer of bone marrow-derived DCs from Tgfbr2(fspKO) mice into 2-week-old syngenic wild-type C57BL/6 mice resulted in reproduction of pancreatitis within 6 weeks. Similar adoptive transfer of wild-type DCs had no effect on pancreas pathology of the host mice. The inability to induce pancreatitis by adoptive transfer of Tgfbr2(fspKO) DCs in adult mice suggested a developmental event in mAIP pathogenesis. Tgfbr2(fspKO) DCs undergo elevated maturation in response to antigen and increased activation of naïve CD4-positive T cells. The development of mAIP in the Tgfbr2(fspKO) mouse model illustrates the role of TGFbeta in maintaining myeloid DC immune tolerance. The loss of immune tolerance in myeloid S100A4(+) DCs can mediate mAIP and may explain some aspects of AIP disease pathogenesis.

  2. Conservation, duplication, and loss of the Tor signaling pathway in the fungal kingdom

    Directory of Open Access Journals (Sweden)

    Heitman Joseph

    2010-09-01

    Full Text Available Abstract Background The nutrient-sensing Tor pathway governs cell growth and is conserved in nearly all eukaryotic organisms from unicellular yeasts to multicellular organisms, including humans. Tor is the target of the immunosuppressive drug rapamycin, which in complex with the prolyl isomerase FKBP12 inhibits Tor functions. Rapamycin is a gold standard drug for organ transplant recipients that was approved by the FDA in 1999 and is finding additional clinical indications as a chemotherapeutic and antiproliferative agent. Capitalizing on the plethora of recently sequenced genomes we have conducted comparative genomic studies to annotate the Tor pathway throughout the fungal kingdom and related unicellular opisthokonts, including Monosiga brevicollis, Salpingoeca rosetta, and Capsaspora owczarzaki. Results Interestingly, the Tor signaling cascade is absent in three microsporidian species with available genome sequences, the only known instance of a eukaryotic group lacking this conserved pathway. The microsporidia are obligate intracellular pathogens with highly reduced genomes, and we hypothesize that they lost the Tor pathway as they adapted and streamlined their genomes for intracellular growth in a nutrient-rich environment. Two TOR paralogs are present in several fungal species as a result of either a whole genome duplication or independent gene/segmental duplication events. One such event was identified in the amphibian pathogen Batrachochytrium dendrobatidis, a chytrid responsible for worldwide global amphibian declines and extinctions. Conclusions The repeated independent duplications of the TOR gene in the fungal kingdom might reflect selective pressure acting upon this kinase that populates two proteinaceous complexes with different cellular roles. These comparative genomic analyses illustrate the evolutionary trajectory of a central nutrient-sensing cascade that enables diverse eukaryotic organisms to respond to their natural

  3. Autoimmune pancreatitis results from loss of TGFβ signalling in S100A4-positive dendritic cells

    Science.gov (United States)

    Boomershine, C S; Chamberlain, A; Kendall, P; Afshar-Sharif, A-R; Huang, H; Washington, M K; Lawson, W E; Thomas, J W; Blackwell, T S; Bhowmick, N A

    2009-01-01

    Background and aims: Autoimmune pancreatitis (AIP) is a poorly understood human disease affecting the exocrine pancreas. The goal of the present study was to elucidate the pathogenic mechanisms underlying pancreatic autoimmunity in a murine disease model. Methods: A transgenic mouse with an S100A4/fibroblast-specific protein 1 (FSP1) Cre-mediated conditional knockout of the transforming growth factor β (TGFβ) type II receptor, termed Tgfbr2fspKO, was used to determine the direct role of TGFβ in S100A4+ cells. Immunohistochemical studies suggested that Tgfbr2fspKO mice develop mouse AIP (mAIP) characterised by interlobular ductal inflammatory infiltrates and pancreatic autoantibody production. Fluorescence-activated cell sorting (FACS)-isolated dendritic cells (DCs) from diseased pancreata were verified to have S100A4-Cre-mediated DNA recombination. Results: The Tgfbr2fspKO mice spontaneously developed mAIP by 6 weeks of age. DCs were confirmed to express S100A4, a previously reported protein expressed by fibroblasts. Adoptive transfer of bone marrow-derived DCs from Tgfbr2fspKO mice into 2-week-old syngenic wild-type C57BL/6 mice resulted in reproduction of pancreatitis within 6 weeks. Similar adoptive transfer of wild-type DCs had no effect on pancreas pathology of the host mice. The inability to induce pancreatitis by adoptive transfer of Tgfbr2fspKO DCs in adult mice suggested a developmental event in mAIP pathogenesis. Tgfbr2fspKO DCs undergo elevated maturation in response to antigen and increased activation of naïve CD4-positive T cells. Conclusion: The development of mAIP in the Tgfbr2fspKO mouse model illustrates the role of TGFβ in maintaining myeloid DC immune tolerance. The loss of immune tolerance in myeloid S100A4+ DCs can mediate mAIP and may explain some aspects of AIP disease pathogenesis. PMID:19625278

  4. Loss of signalling via Gα13 in germinal centre B-cell-derived lymphoma.

    Science.gov (United States)

    Muppidi, Jagan R; Schmitz, Roland; Green, Jesse A; Xiao, Wenming; Larsen, Adrien B; Braun, Sterling E; An, Jinping; Xu, Ying; Rosenwald, Andreas; Ott, German; Gascoyne, Randy D; Rimsza, Lisa M; Campo, Elias; Jaffe, Elaine S; Delabie, Jan; Smeland, Erlend B; Braziel, Rita M; Tubbs, Raymond R; Cook, J R; Weisenburger, Dennis D; Chan, Wing C; Vaidehi, Nagarajan; Staudt, Louis M; Cyster, Jason G

    2014-12-11

    Germinal centre B-cell-like diffuse large B-cell lymphoma (GCB-DLBCL) is a common malignancy, yet the signalling pathways that are deregulated and the factors leading to its systemic dissemination are poorly defined. Work in mice showed that sphingosine-1-phosphate receptor-2 (S1PR2), a Gα12 and Gα13 coupled receptor, promotes growth regulation and local confinement of germinal centre B cells. Recent deep sequencing studies of GCB-DLBCL have revealed mutations in many genes in this cancer, including in GNA13 (encoding Gα13) and S1PR2 (refs 5,6, 7). Here we show, using in vitro and in vivo assays, that GCB-DLBCL-associated mutations occurring in S1PR2 frequently disrupt the receptor's Akt and migration inhibitory functions. Gα13-deficient mouse germinal centre B cells and human GCB-DLBCL cells were unable to suppress pAkt and migration in response to S1P, and Gα13-deficient mice developed germinal centre B-cell-derived lymphoma. Germinal centre B cells, unlike most lymphocytes, are tightly confined in lymphoid organs and do not recirculate. Remarkably, deficiency in Gα13, but not S1PR2, led to germinal centre B-cell dissemination into lymph and blood. GCB-DLBCL cell lines frequently carried mutations in the Gα13 effector ARHGEF1, and Arhgef1 deficiency also led to germinal centre B-cell dissemination. The incomplete phenocopy of Gα13- and S1PR2 deficiency led us to discover that P2RY8, an orphan receptor that is mutated in GCB-DLBCL and another germinal centre B-cell-derived malignancy, Burkitt's lymphoma, also represses germinal centre B-cell growth and promotes confinement via Gα13. These findings identify a Gα13-dependent pathway that exerts dual actions in suppressing growth and blocking dissemination of germinal centre B cells that is frequently disrupted in germinal centre B-cell-derived lymphoma.

  5. The loss of Drosophila APG4/AUT2 function modifies the phenotypes of cut and Notch signaling pathway mutants.

    Science.gov (United States)

    Thumm, M; Kadowaki, T

    2001-12-01

    A P-element line ( P0997) of Drosophila melanogaster in which the P element disrupts the Drosophila homolog of the Saccharomyces cerevisiae gene APG4/AUT2 was identified during the course of screening for cut ( ct) modifiers. The yeast gene APG4/AUT2 encodes a cysteine endoprotease directed against Apg8/Aut7 and is necessary for autophagy. The P0997 mutation enhances the wing margin loss associated with ct mutations, and also modifies the wing and eye phenotypes of Notch (N), Serrate (Ser), Delta (Dl), Hairless (H), deltex (dx), vestigial (vg) and strawberry notch (sno) mutants. These results therefore suggest an unexpected link between autophagy and the Notch signaling pathway.

  6. Loss of tumor suppressor Merlin results in aberrant activation of Wnt/β-catenin signaling in cancer.

    Science.gov (United States)

    Morrow, K Adam; Das, Shamik; Meng, Erhong; Menezes, Mitchell E; Bailey, Sarah K; Metge, Brandon J; Buchsbaum, Donald J; Samant, Rajeev S; Shevde, Lalita A

    2016-04-05

    The expression of the tumor suppressor Merlin is compromised in nervous system malignancies due to genomic aberrations. We demonstrated for the first time, that in breast cancer, Merlin protein expression is lost due to proteasome-mediated elimination. Immunohistochemical analysis of tumor tissues from patients with metastatic breast cancer revealed characteristically reduced Merlin expression. Importantly, we identified a functional role for Merlin in impeding breast tumor xenograft growth and reducing invasive characteristics. We sought to determine a possible mechanism by which Merlin accomplishes this reduction in malignant activity. We observed that breast and pancreatic cancer cells with loss of Merlin show an aberrant increase in the activity of β-catenin concomitant with nuclear localization of β-catenin. We discovered that Merlin physically interacts with β-catenin, alters the sub-cellular localization of β-catenin, and significantly reduces the protein levels of β-catenin by targeting it for degradation through the upregulation of Axin1. Consequently, restoration of Merlin inhibited β-catenin-mediated transcriptional activity in breast and pancreatic cancer cells. We also present evidence that loss of Merlin sensitizes tumor cells to inhibition by compounds that target β-catenin-mediated activity. Thus, this study provides compelling evidence that Merlin reduces the malignant activity of pancreatic and breast cancer, in part by suppressing the Wnt/β-catenin pathway. Given the potent role of Wnt/β-catenin signaling in breast and pancreatic cancer and the flurry of activity to test β-catenin inhibitors in the clinic, our findings are opportune and provide evidence for Merlin in restraining aberrant activation of Wnt/β-catenin signaling.

  7. Signal detection in industrial noise: effects of noise exposure history, hearing loss, and the use of ear protection.

    Science.gov (United States)

    Abel, S M; Kunov, H; Pichora-Fuller, M K; Alberti, P W

    1985-01-01

    The detection of one-third octave signals superimposed on backgrounds of steady-state and intermittent industrial noise of 84 dBA was investigated for observers with normal hearing or moderate to severe noise-induced hearing loss (NIHL). Variables included age, noise exposure history, configuration of the audiogram and the wearing of insert hearing protectors. Detection thresholds were obtained binaurally over headphones using a two- interval forced-choice procedure. For unprotected listening all observers showed a masked threshold of about 80 dBA for a one-third octave band cented at 3.15 kHz. Neither variation in noise exposure history nor configuration of the audiogram were significant factors. Using insert protectors in noise, observers with normal hearing showed an advantage on average of 3 dB. Those with NIHL gave masked detection thresholds greater than 100 dBA. Detection of a one-third octave band centred at 1 kHz by hearing-impaired observers with mild to moderate loss at 1 kHz was similar to that for normal observers. A model of the detection process was developed and evaluated.

  8. Challenges of arbitrary waveform signal detection by Silicon Photomultipliers as readout for Cherenkov fibre based beam loss monitoring systems

    CERN Document Server

    Vinogradov, Sergey; Nebot del Busto, Eduardo; Kastriotou, Maria; Welsch, Carsten P

    2016-01-01

    Silicon Photomultipliers (SiPMs) are well recognised as very competitive photodetectors due to their exceptional photon number and time resolution, room-temperature low-voltage operation, insensitivity to magnetic fields, compactness, and robustness. Detection of weak light pulses of nanosecond time scale appears to be the best area for SiPM applications because in this case most of the SiPM drawbacks have a rather limited effect on its performance. In contrast to the more typical scintillation and Cherenkov detection applications, which demand information on the number of photons and/or the arrival time of the light pulse only, beam loss monitoring (BLM) systems utilising Cherenkov fibres with photodetector readout have to precisely reconstruct the temporal profile of the light pulse. This is a rather challenging task for any photon detector especially taking into account the high dynamic range of incident signals (100K – 1M) from a few photons to a few percents of destructive losses in a beam line and pre...

  9. Marrow adipogenesis and bone loss that parallels estrogen deficiency is slowed by low-intensity mechanical signals.

    Science.gov (United States)

    Krishnamoorthy, D; Frechette, D M; Adler, B J; Green, D E; Chan, M E; Rubin, C T

    2016-02-01

    Ovariectomized mice were used to assess the ability of low-intensity vibrations to protect bone microarchitecture and marrow composition. Results indicate that low-intensity vibrations (LIV), introduced 2 weeks postsurgery, slows marrow adipogenesis in OVX mice but does not restore the bone within the period studied. However, immediate application of LIV partially protects quality. The aim of this study was to evaluate consequences of estrogen depletion on bone marrow (BM) phenotype and bone microarchitecture, and effects of mechanical signals delivered as LIV on modulating these changes. LIV (0.3 g, 90 Hz) was applied to C57BL/6 mice immediately following ovariectomy or 2 weeks postestrogen withdrawal for 2 (ST-LIV) or 6 weeks (LT-LIV), respectively. Sham-operated age-matched controls (ST-AC, LT-AC) and ovariectomized controls (ST-OVX, LT-OVX) received sham LIV treatment. Bone microstructure was evaluated through μCT and BM adipogenesis through histomorphometry, serum markers, and genes expression analysis. LT-OVX increased BM adipogenesis relative to LT-AC (+136 %, p ≤ 0.05), while LT-LIV introduced for 6w suppressed this adipose encroachment (-55 %, p ≤ 0.05). In parallel with the fatty marrow, LT-OVX showed a marked loss of trabecular bone, -40 % (p ≤ 0.05) in the first 2 weeks following ovariectomy compared to LT-AC. Application of LT-LIV for 6w following this initial 2w bone loss failed to restore the lost trabeculae but did initiate an anabolic response as indicated by increased serum alkaline phosphatase (+26 %, p ≤ 0.05). In contrast, application of LIV immediately following ovariectomy was more efficacious in the protection of trabecular bone, with a +29 % (p > 0.05) greater BV/TV compared to ST-OVX at the 2w time period. LIV can mitigate adipocyte accumulation in OVX marrow and protect it by favoring osteoblastogenesis over adipogenesis. These data also emphasize the rapidity of bone loss with OVX and provide

  10. Ploidy status and copy number aberrations in primary glioblastomas defined by integrated analysis of allelic ratios, signal ratios and loss of heterozygosity using 500K SNP Mapping Arrays

    Directory of Open Access Journals (Sweden)

    Cowell John K

    2008-10-01

    Full Text Available Abstract Background Genomic hybridization platforms, including BAC-CGH and genotyping arrays, have been used to estimate chromosome copy number (CN in tumor samples by detecting the relative strength of genomic signal. The methods rely on the assumption that the predominant chromosomal background of the samples is diploid, an assumption that is frequently incorrect for tumor samples. In addition to generally greater resolution, an advantage of genotyping arrays over CGH arrays is the ability to detect signals from individual alleles, allowing estimation of loss-of-heterozygosity (LOH and allelic ratios to enhance the interpretation of copy number alterations. Copy number events associated with LOH potentially have the same genetic consequences as deletions. Results We have utilized allelic ratios to detect patterns that are indicative of higher ploidy levels. An integrated analysis using allelic ratios, total signal and LOH indicates that many or most of the chromosomes from 24 glioblastoma tumors are in fact aneuploid. Some putative whole-chromosome losses actually represent trisomy, and many apparent sub-chromosomal losses are in fact relative losses against a triploid or tetraploid background. Conclusion These results suggest a re-interpretation of previous findings based only on total signal ratios. One interesting observation is that many single or multiple-copy deletions occur at common putative tumor suppressor sites subsequent to chromosomal duplication; these losses do not necessarily result in LOH, but nonetheless occur in conspicuous patterns. The 500 K Mapping array was also capable of detecting many sub-mega base losses and gains that were overlooked by CGH-BAC arrays, and was superior to CGH-BAC arrays in resolving regions of complex CN variation.

  11. Loss of Endogenous Interleukin-12 Activates Survival Signals in Ultraviolet-Exposed Mouse Skin and Skin Tumors

    Directory of Open Access Journals (Sweden)

    Syed M. Meeran

    2009-09-01

    Full Text Available Interleukin-12 (IL-12-deficiency promotes photocarcinogenesis in mice; however, the molecular mechanisms underlying this effect have not been fully elucidated. Here, we report that long-term exposure to ultraviolet (UV radiation resulted in enhancement of the levels of cell survival kinases, such as phosphatidylinositol 3-kinase (PI3K, Akt (Ser473, p-ERK1/2, and p-p38 in the skin of IL-12p40 knockout (IL-12 KO mice compared with the skin of wild-type mice. UV-induced activation of nuclear factor-κB (NF-κB/p65 in the skin of IL-12 KO mice was also more prominent. The levels of NF-κB-targeted proteins, such as proliferating cell nuclear antigen (PCNA, cyclooxygenase-2, cyclin D1, and inducible nitric oxide synthase, were higher in the UV-exposed skin of IL-12 KO mice than the UV-exposed skin of wild types. In short-term UV irradiation experiments, subcutaneous treatment of IL-12 KO mice with recombinant IL-12 (rIL-12 or topical treatment with oridonin, an inhibitor of NF-κB, resulted in the inhibition of UV-induced increases in the levels of PCNA, cyclin D1, and NF-κB compared with non-rIL-12- or non-oridonin-treated IL-12 KO mice. UV-induced skin tumors of IL-12 KO mice had higher levels of PI3K, p-Akt (Ser473, p-ERK1/2, p-p38, NF-κB, and PCNA and fewer apoptotic cells than skin tumors of wild types. Together, these data suggest that the loss of endogenous IL-12 activates survival signals in UV-exposed skin and that may lead to the enhanced photocarcinogenesis in mice.

  12. Loss of the Drosophila cell polarity regulator Scribbled promotes epithelial tissue overgrowth and cooperation with oncogenic Ras-Raf through impaired Hippo pathway signaling

    Directory of Open Access Journals (Sweden)

    Grusche Felix A

    2011-09-01

    Full Text Available Abstract Background Epithelial neoplasias are associated with alterations in cell polarity and excessive cell proliferation, yet how these neoplastic properties are related to one another is still poorly understood. The study of Drosophila genes that function as neoplastic tumor suppressors by regulating both of these properties has significant potential to clarify this relationship. Results Here we show in Drosophila that loss of Scribbled (Scrib, a cell polarity regulator and neoplastic tumor suppressor, results in impaired Hippo pathway signaling in the epithelial tissues of both the eye and wing imaginal disc. scrib mutant tissue overgrowth, but not the loss of cell polarity, is dependent upon defective Hippo signaling and can be rescued by knockdown of either the TEAD/TEF family transcription factor Scalloped or the transcriptional coactivator Yorkie in the eye disc, or reducing levels of Yorkie in the wing disc. Furthermore, loss of Scrib sensitizes tissue to transformation by oncogenic Ras-Raf signaling, and Yorkie-Scalloped activity is required to promote this cooperative tumor overgrowth. The inhibition of Hippo signaling in scrib mutant eye disc clones is not dependent upon JNK activity, but can be significantly rescued by reducing aPKC kinase activity, and ectopic aPKC activity is sufficient to impair Hippo signaling in the eye disc, even when JNK signaling is blocked. In contrast, warts mutant overgrowth does not require aPKC activity. Moreover, reducing endogenous levels of aPKC or increasing Scrib or Lethal giant larvae levels does not promote increased Hippo signaling, suggesting that aPKC activity is not normally rate limiting for Hippo pathway activity. Epistasis experiments suggest that Hippo pathway inhibition in scrib mutants occurs, at least in part, downstream or in parallel to both the Expanded and Fat arms of Hippo pathway regulation. Conclusions Loss of Scrib promotes Yorkie/Scalloped-dependent epithelial tissue

  13. MTOR signaling and ubiquitin-proteosome gene expression in the preservation of fat free mass following high protein, calorie restricted weight loss

    Directory of Open Access Journals (Sweden)

    McIver Cassandra M

    2012-09-01

    Full Text Available Abstract Caloric restriction is one of the most efficient ways to promote weight loss and is known to activate protective metabolic pathways. Frequently reported with weight loss is the undesirable consequence of fat free (lean muscle mass loss. Weight loss diets with increased dietary protein intake are popular and may provide additional benefits through preservation of fat free mass compared to a standard protein, high carbohydrate diet. However, the precise mechanism by which a high protein diet may mitigate dietary weight loss induced reductions in fat free mass has not been fully elucidated. Maintenance of fat free mass is dependent upon nutrient stimulation of protein synthesis via the mTOR complex, although during caloric restriction a decrease (atrophy in skeletal muscle may be driven by a homeostatic shift favouring protein catabolism. This review evaluates the relationship between the macronutrient composition of calorie restricted diets and weight loss using metabolic indicators. Specifically we evaluate the effect of increased dietary protein intake and caloric restricted diets on gene expression in skeletal muscle, particularly focusing on biosynthesis, degradation and the expression of genes in the ubiquitin-proteosome (UPP and mTOR signaling pathways, including MuRF-1, MAFbx/atrogin-1, mTORC1, and S6K1.

  14. Near-zero dispersion flattened, low-loss porous-core waveguide design for terahertz signal transmission

    Science.gov (United States)

    Sultana, Jakeya; Islam, Md. Saiful; Atai, Javid; Islam, Muhammad Rakibul; Abbott, Derek

    2017-07-01

    We demonstrate a photonic crystal fiber with near-zero flattened dispersion, ultralower effective material loss (EML), and negligible confinement loss for a broad spectrum range. The use of cyclic olefin copolymer Topas with improved core confinement significantly reduces the loss characteristics and the use of higher air filling fraction results in flat dispersion characteristics. The properties such as dispersion, EML, confinement loss, modal effective area, and single-mode operation of the fiber have been investigated using the full-vector finite element method with the perfectly matched layer absorbing boundary conditions. The practical implementation of the proposed fiber is achievable with existing fabrication techniques as only circular-shaped air holes have been used to design the waveguide. Thus, it is expected that the proposed terahertz waveguide can potentially be used for flexible and efficient transmission of terahertz waves.

  15. Severe signal loss in diamond beam loss monitors in high particle rate environments by charge trapping in radiation-induced defects

    CERN Document Server

    Kassel, Florian; Dabrowski, Anne; de Boer, Wim

    2016-01-01

    The beam condition monitoring leakage (BCML) system is a beam monitoring device in the compact muon solenoid (CMS) experiment at the large hadron collider (LHC). As detectors 32 poly-crystalline (pCVD) diamond sensors are positioned in rings around the beam pipe. Here, high particle rates occur from the colliding beams scattering particles outside the beam pipe. These particles cause defects, which act as traps for the ionization, thus reducing the charge collection efficiency (CCE). However, the loss in CCE was much more severe than expected from low rate laboratory measurements and simulations, especially in single-crystalline (sCVD) diamonds, which have a low initial concentration of defects. The reason why in real experiments the CCE is much worse than in laboratory experiments is related to the ionization rate. At high particle rates the trapping rate of the ionization is so high compared with the detrapping rate, that space charge builds up. This space charge reduces locally the internal electric field,...

  16. Decoupled temporal variability and signal synchronization of spontaneous brain activity in loss of consciousness: An fMRI study in anesthesia.

    Science.gov (United States)

    Huang, Zirui; Zhang, Jun; Wu, Jinsong; Qin, Pengmin; Wu, Xuehai; Wang, Zhiyao; Dai, Rui; Li, Yuan; Liang, Weimin; Mao, Ying; Yang, Zhong; Zhang, Jianfeng; Wolff, Annemarie; Northoff, Georg

    2016-01-01

    Two aspects of the low frequency fluctuations of spontaneous brain activity have been proposed which reflect the complex and dynamic features of resting-state activity, namely temporal variability and signal synchronization. The relationship between them, especially its role in consciousness, nevertheless remains unclear. Our study examined the temporal variability and signal synchronization of spontaneous brain activity, as well as their relationship during loss of consciousness. We applied an intra-subject design of resting-state functional magnetic resonance imaging (rs-fMRI) in two conditions: during wakefulness, and under anesthesia with clinical unconsciousness. In addition, an independent group of patients with disorders of consciousness (DOC) was included in order to test the reliability of our findings. We observed a global reduction in the temporal variability, local and distant brain signal synchronization for subjects during anesthesia. Importantly, we found a link between temporal variability and both local and distant signal synchronizations during wakefulness: the higher the degree of temporal variability, the higher its intra-regional homogeneity and inter-regional functional connectivity. In contrast, this link was broken down under anesthesia, implying a decoupling between temporal variability and signal synchronization; this decoupling was reproduced in patients with DOC. Our results suggest that there exist some as yet unclear physiological mechanisms of consciousness which "couple" the two mathematically independent measures, temporal variability and signal synchronization of spontaneous brain activity. Our findings not only extend our current knowledge of the neural correlates of anesthetic-induced unconsciousness, but have implications for both computational neural modeling and clinical practice, such as in the diagnosis of loss of consciousness in patients with DOC. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Cobalt Alloy Implant Debris Induces Inflammation and Bone Loss Primarily through Danger Signaling, Not TLR4 Activation: Implications for DAMP-ening Implant Related Inflammation.

    Science.gov (United States)

    Samelko, Lauryn; Landgraeber, Stefan; McAllister, Kyron; Jacobs, Joshua; Hallab, Nadim James

    2016-01-01

    Cobalt alloy debris has been implicated as causative in the early failure of some designs of current total joint implants. The ability of implant debris to cause excessive inflammation via danger signaling (NLRP3 inflammasome) vs. pathogen associated pattern recognition receptors (e.g. Toll-like receptors; TLRs) remains controversial. Recently, specific non-conserved histidines on human TLR4 have been shown activated by cobalt and nickel ions in solution. However, whether this TLR activation is directly or indirectly an effect of metals or secondary endogenous alarmins (danger-associated molecular patterns, DAMPs) elicited by danger signaling, remains unknown and contentious. Our study indicates that in both a human macrophage cell line (THP-1) and primary human macrophages, as well as an in vivo murine model of inflammatory osteolysis, that Cobalt-alloy particle induced NLRP3 inflammasome danger signaling inflammatory responses were highly dominant relative to TLR4 activation, as measured respectively by IL-1β or TNF-α, IL-6, IL-10, tissue histology and quantitative bone loss measurement. Despite the lack of metal binding histidines H456 and H458 in murine TLR4, murine calvaria challenge with Cobalt alloy particles induced significant macrophage driven in vivo inflammation and bone loss inflammatory osteolysis, whereas LPS calvaria challenge alone did not. Additionally, no significant increase (p500pg/mL). Therefore, not only do the results of this investigation support Cobalt alloy danger signaling induced inflammation, but under normal homeostasis low levels of hematogenous PAMPs (<2pg/mL) from Gram-negative bacteria, seem to have negligible contribution to the danger signaling responses elicited by Cobalt alloy metal implant debris. This suggests the unique nature of Cobalt alloy particle bioreactivity is strong enough to illicit danger signaling that secondarily activate concomitant TLR activation, and may in part explain Cobalt particulate associated

  18. NOX3 NADPH oxidase couples transient receptor potential vanilloid 1 to signal transducer and activator of transcription 1-mediated inflammation and hearing loss.

    Science.gov (United States)

    Mukherjea, Debashree; Jajoo, Sarvesh; Sheehan, Kelly; Kaur, Tejbeer; Sheth, Sandeep; Bunch, Jennifer; Perro, Christopher; Rybak, Leonard P; Ramkumar, Vickram

    2011-03-15

    Transient receptor potential vanilloid 1 (TRPV1) is implicated in cisplatin ototoxicity. Activation of this channel by cisplatin increases reactive oxygen species generation, which contribute to loss of outer hair cells in the cochlea. Knockdown of TRPV1 by short interfering RNA protected against cisplatin ototoxicity. In this study, we examined the mechanism underlying TRPV1-mediated ototoxicity using cultured organ of Corti transformed cells (UB/OC-1) and rats. Trans-tympanic injections of capsaicin produced transient hearing loss within 24 h, which recovered by 72 h. In UB/OC-1 cells, capsaicin increased NOX3 NADPH oxidase activity and activation of signal transducer and activator of transcription 1 (STAT1). Intratympanic administration of capsaicin transiently increased STAT1 activity and expression of downstream proinflammatory molecules. Capsaicin produced a transient increase in CD14-positive inflammatory cells into the cochlea, which mimicked the temporal course of STAT1 activation but did not alter the expression of apoptotic genes or damage to outer hair cells. In addition, trans-tympanic administration of STAT1 short interfering RNA protected against capsaicin-induced hearing loss. These data suggest that activation of TRPV1 mediates temporary hearing loss by initiating an inflammatory process in the cochlea via activation of NOX3 and STAT1. Thus, these proteins represent reasonable targets for ameliorating hearing loss.

  19. Severe signal loss in diamond beam loss monitors in high particle rate environments by charge trapping in radiation-induced defects

    Energy Technology Data Exchange (ETDEWEB)

    Kassel, Florian; Boer, Wim de [Institute for Experimental Nuclear Physics (IEKP), KIT, Karlsruhe (Germany); Guthoff, Moritz; Dabrowski, Anne [CERN, Meyrin (Switzerland)

    2016-10-15

    The beam condition monitoring leakage (BCML) system is a beam monitoring device in the compact muon solenoid (CMS) experiment at the large hadron collider (LHC). As detectors 32 poly-crystalline (pCVD) diamond sensors are positioned in rings around the beam pipe. Here, high particle rates occur from the colliding beams scattering particles outside the beam pipe. These particles cause defects, which act as traps for the ionization, thus reducing the charge collection efficiency (CCE). However, the loss in CCE was much more severe than expected from low rate laboratory measurements and simulations, especially in single-crystalline (sCVD) diamonds, which have a low initial concentration of defects. After an integrated luminosity of a few fb{sup -1} corresponding to a few weeks of LHC operation, the CCE of the sCVD diamonds dropped by a factor of five or more and quickly approached the poor CCE of pCVD diamonds. The reason why in real experiments the CCE is much worse than in laboratory experiments is related to the ionization rate. At high particle rates the trapping rate of the ionization is so high compared with the detrapping rate, that space charge builds up. This space charge reduces locally the internal electric field, which in turn increases the trapping rate and recombination and hence reduces the CCE in a strongly non-linear way. A diamond irradiation campaign was started to investigate the rate-dependent electrical field deformation with respect to the radiation damage. Besides the electrical field measurements via the transient current technique (TCT), the CCE was measured. The experimental results were used to create an effective deep trap model that takes the radiation damage into account. Using this trap model, the rate-dependent electrical field deformation and the CCE were simulated with the software SILVACO TCAD. The simulation, tuned to rate-dependent measurements from a strong radioactive source, was able to predict the non-linear decrease of the

  20. Loss of cytokine-STAT5 signaling in the CNS and pituitary gland alters energy balance and leads to obesity.

    Directory of Open Access Journals (Sweden)

    Ji-Yeon Lee

    Full Text Available Signal transducers and activators of transcription (STATs are critical components of cytokine signaling pathways. STAT5A and STAT5B (STAT5, the most promiscuous members of this family, are highly expressed in specific populations of hypothalamic neurons in regions known to mediate the actions of cytokines in the regulation of energy balance. To test the hypothesis that STAT5 signaling is essential to energy homeostasis, we used Cre-mediated recombination to delete the Stat5 locus in the CNS. Mutant males and females developed severe obesity with hyperphagia, impaired thermal regulation in response to cold, hyperleptinemia and insulin resistance. Furthermore, central administration of GM-CSF mediated the nuclear accumulation of STAT5 in hypothalamic neurons and reduced food intake in control but not in mutant mice. These results demonstrate that STAT5 mediates energy homeostasis in response to endogenous cytokines such as GM-CSF.

  1. Gα and regulator of G-protein signaling (RGS) protein pairs maintain functional compatibility and conserved interaction interfaces throughout evolution despite frequent loss of RGS proteins in plants.

    Science.gov (United States)

    Hackenberg, Dieter; McKain, Michael R; Lee, Soon Goo; Roy Choudhury, Swarup; McCann, Tyler; Schreier, Spencer; Harkess, Alex; Pires, J Chris; Wong, Gane Ka-Shu; Jez, Joseph M; Kellogg, Elizabeth A; Pandey, Sona

    2017-10-01

    Signaling pathways regulated by heterotrimeric G-proteins exist in all eukaryotes. The regulator of G-protein signaling (RGS) proteins are key interactors and critical modulators of the Gα protein of the heterotrimer. However, while G-proteins are widespread in plants, RGS proteins have been reported to be missing from the entire monocot lineage, with two exceptions. A single amino acid substitution-based adaptive coevolution of the Gα:RGS proteins was proposed to enable the loss of RGS in monocots. We used a combination of evolutionary and biochemical analyses and homology modeling of the Gα and RGS proteins to address their expansion and its potential effects on the G-protein cycle in plants. Our results show that RGS proteins are widely distributed in the monocot lineage, despite their frequent loss. There is no support for the adaptive coevolution of the Gα:RGS protein pair based on single amino acid substitutions. RGS proteins interact with, and affect the activity of, Gα proteins from species with or without endogenous RGS. This cross-functional compatibility expands between the metazoan and plant kingdoms, illustrating striking conservation of their interaction interface. We propose that additional proteins or alternative mechanisms may exist which compensate for the loss of RGS in certain plant species. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.

  2. Chronic overload induced hypertrophy is associated with age-related muscle mass loss and diminished mTOR signaling

    Science.gov (United States)

    The purpose of this study was to assess activation of the mTOR signaling pathway in young and aging rats in response to chronic muscle overload. Young (6 mo; n = 16) and older (30 mo; n = 23) male rats (F344xBN) were subjected to 4 weeks of bilateral surgical ablation (SA) of two-thirds of the gastr...

  3. Regulators of G protein signaling 12 (Rgs12) promotes osteoclastogenesis in bone remodeling and pathologic bone loss

    Science.gov (United States)

    Calcium (Ca2+) signaling plays a pivotal role in controlling various cellular processes such as secretion, differentiation, proliferation, motility, and cell death through the release of Ca2+ from internal stores and entry from extracellular fluid. In bone, receptor activator of NF-kB ligand (RANKL)...

  4. Loss of epithelial Gq and G11 signaling inhibits TGFβ production but promotes IL-33-mediated macrophage polarization and emphysema.

    Science.gov (United States)

    John, Alison E; Wilson, Michael R; Habgood, Anthony; Porte, Joanne; Tatler, Amanda L; Stavrou, Anastasios; Miele, Gino; Jolly, Lisa; Knox, Alan J; Takata, Masao; Offermanns, Stefan; Jenkins, R Gisli

    2016-10-25

    Heterotrimeric guanine nucleotide-binding protein (G protein) signaling links hundreds of G protein-coupled receptors with four G protein signaling pathways. Two of these, one mediated by Gq and G11 (Gq/11) and the other by G12 and G13 (G12/13), are implicated in the force-dependent activation of transforming growth factor-β (TGFβ) in lung epithelial cells. Reduced TGFβ activation in alveolar cells leads to emphysema, whereas enhanced TGFβ activation promotes acute lung injury and idiopathic pulmonary fibrosis. Therefore, precise control of alveolar TGFβ activation is essential for alveolar homeostasis. We investigated the involvement of the Gq/11 and G12/13 pathways in epithelial cells in generating active TGFβ and regulating alveolar inflammation. Mice deficient in both Gαq and Gα11 developed inflammation that was primarily caused by alternatively activated (M2-polarized) macrophages, enhanced matrix metalloproteinase 12 (MMP12) production, and age-related alveolar airspace enlargement consistent with emphysema. Mice with impaired Gq/11 signaling had reduced stretch-mediated generation of TGFβ by epithelial cells and enhanced macrophage MMP12 synthesis but were protected from the effects of ventilator-induced lung injury. Furthermore, synthesis of the cytokine interleukin-33 (IL-33) was increased in these alveolar epithelial cells, resulting in the M2-type polarization of alveolar macrophages independently of the effect on TGFβ. Our results suggest that alveolar Gq/11 signaling maintains alveolar homeostasis and likely independently increases TGFβ activation in response to the mechanical stress of the epithelium and decreases epithelial IL-33 synthesis. Together, these findings suggest that disruption of Gq/11 signaling promotes inflammatory emphysema but protects against mechanically induced lung injury. Copyright © 2016, American Association for the Advancement of Science.

  5. A loss-of-function mutation in the nucleoporin AtNUP160 indicates that normal auxin signalling is required for a proper ethylene response in Arabidopsis

    Science.gov (United States)

    Robles, Linda M.; Deslauriers, Stephen D.; Alvarez, Ashley A.; Larsen, Paul B.

    2012-01-01

    As part of a continuing effort to elucidate mechanisms that regulate the magnitude of ethylene signalling, an Arabidopsis mutant with an enhanced ethylene response was identified. Subsequent characterization of this loss-of-function mutant revealed severe hypocotyl shortening in the presence of saturating ethylene along with increased expression in leaves of a subset of ethylene-responsive genes. It was subsequently determined by map-based cloning that the mutant (sar1-7) represents a loss-of-function mutation in the previously described nucleoporin AtNUP160 (At1g33410, SAR1). In support of previously reported results, the sar1-7 mutant partially restored auxin responsiveness to roots of an rce1 loss-of-function mutant, indicating that AtNUP160/SAR1 is required for proper expression of factors responsible for the repression of auxin signalling. Analysis of arf7-1/sar1-7 and arf19-1/sar1-7 double mutants revealed that mutations affecting either ARF7 or ARF19 function almost fully blocked manifestation of the sar1-7-dependent ethylene hypersensitivity phenotype, suggesting that ARF7- and ARF19-mediated auxin signalling is responsible for regulating the magnitude of and/or competence for the ethylene response in Arabidopsis etiolated hypocotyls. Consistent with this, addition of auxin to ethylene-treated seedlings resulted in severe hypocotyl shortening, reminiscent of that seen for other eer (enhanced ethylene response) mutants, suggesting that auxin functions in part synergistically with ethylene to control hypocotyl elongation and other ethylene-dependent phenomena. PMID:22238449

  6. Comparison of performance of transcranial contralateral routing of signal, pre-implanted trimmer digital and digital bone anchored hearing aid in adults with unilateral hearing loss

    Directory of Open Access Journals (Sweden)

    Neelamegarajan Devi

    2015-06-01

    Full Text Available Individuals with unilateral hearing loss of severe-profound degree face listening difficulties while localizing a sound source and while perceiving speech in the presence of noise. The objective was to compare the efficacy of the digitally programmable bone anchored hearing aid (BAHA, trimmer digital BAHA and the transcranial contralateral routing of signal (T-CROS in improving the listening performance in adults with unilateral hearing loss. Twenty-four adults with unilateral hearing loss was assessed for sound field thresholds, speech perception performance in quiet and noise (direct and indirect conditions and the subjective quality rating of speech in unaided and aided with either T-CROS or digitally programmable BAHA or trimmer digital BAHA attached to the headband. Results indicated that the participants performed better with both the digitally programmable and the trimmer digital BAHA than the T-CROS in both quiet and noise. However, the digitally programmable BAHA performed better when the speech arrived from the poorer ear side. The current study helps in prioritizing the hearing amplification devices for the trial and also helps in arriving at the appropriate hearing amplification device for the individuals with unilateral hearing loss.

  7. Comparison of Performance of Transcranial Contralateral Routing of Signal, Pre-Implanted Trimmer Digital and Digital Bone Anchored Hearing Aid in Adults with Unilateral Hearing Loss.

    Science.gov (United States)

    Devi, Neelamegarajan; Chatni, Suma; Ramadevi, Kasetty Jagannathaiah S; Fakruddin, Darga Baba

    2015-06-11

    Individuals with unilateral hearing loss of severe-profound degree face listening difficulties while localizing a sound source and while perceiving speech in the presence of noise. The objective was to compare the efficacy of the digitally programmable bone anchored hearing aid (BAHA), trimmer digital BAHA and the transcranial contralateral routing of signal (T-CROS) in improving the listening performance in adults with unilateral hearing loss. Twenty-four adults with unilateral hearing loss was assessed for sound field thresholds, speech perception performance in quiet and noise (direct and indirect conditions) and the subjective quality rating of speech in unaided and aided with either T-CROS or digitally programmable BAHA or trimmer digital BAHA attached to the headband. Results indicated that the participants performed better with both the digitally programmable and the trimmer digital BAHA than the T-CROS in both quiet and noise. However, the digitally programmable BAHA performed better when the speech arrived from the poorer ear side. The current study helps in prioritizing the hearing amplification devices for the trial and also helps in arriving at the appropriate hearing amplification device for the individuals with unilateral hearing loss.

  8. Truncated ErbB2 receptor enhances ErbB1 signaling and induces reversible, ERK-independent loss of epithelial morphology

    DEFF Research Database (Denmark)

    Egeblad, M; Mortensen, Ole Hartvig; Jäättelä, M

    2001-01-01

    Shedding of the extracellular domain of the ErbB2 tyrosine kinase receptor and expression of the remaining NH(2)-terminally truncated ErbB2 correlates with lymph node metastases and adverse outcome in human breast cancer. To study the possible signaling from such a truncated receptor, MCF-7 human...... breast cancer cells expressing NH(2)-terminally truncated ErbB2 (DeltaNErbB2) were compared with cells overexpressing wild-type ErbB2. Expression of DeltaNErbB2 in MCF-7 cells resulted in sustained activation of extracellular signal-regulated kinases (ERK) 1/2, extensive loss of the epithelial morphology......, appearance of vesicles and long protrusions as well as pronounced scattering of the cells. Similar alterations were observed upon ErbB2 overexpression but at much lower levels. Employing cell clones with inducible expression of DeltaNErbB2, it was revealed that the morphological changes were fully reversible...

  9. Differential effects of maternal obesity and weight loss in the periconceptional period on the epigenetic regulation of hepatic insulin-signaling pathways in the offspring.

    Science.gov (United States)

    Nicholas, Lisa M; Rattanatray, Leewen; MacLaughlin, Severence M; Ozanne, Susan E; Kleemann, Dave O; Walker, Simon K; Morrison, Janna L; Zhang, Song; Muhlhäusler, Beverley S; Martin-Gronert, Malgorzata S; McMillen, Isabella C

    2013-09-01

    Our aim was to determine the effect of exposure to maternal obesity or to maternal weight loss around conception on the programming of hepatic insulin signaling in the offspring. We used an embryo transfer model in sheep to investigate the effects of exposure to either maternal obesity or to weight loss in normal and obese mothers preceding and for 1 wk after conception on the expression of hepatic insulin-signaling and gluconeogenic factors and key miRNAs involved in insulin signaling in the offspring. We found that exposure to maternal obesity resulted in increased hepatic miR-29b (P<0.05), miR-103 (P<0.01), and miR-107 (P<0.05) expression, a decrease in IR (P<0.05), phopsho-Akt (P<0.01), and phospho-FoxO1 (P<0.01) abundance, and a paradoxical decrease in 11βHSD1 (P<0.05), PEPCK-C (P<0.01), and PEPCK-M (P<0.05) expression in lambs. These changes were ablated by a period of moderate dietary restriction imposed during the periconceptional period. Maternal dietary restriction alone also resulted in decreased abundance of a separate subset of hepatic insulin-signaling molecules, namely, IRS1 (P<0.05), PDK1 (P<0.01), phospho-PDK1 (P<0.05), and aPKCζ (P<0.05) and in decreased PEPCK-C (P<0.01) and G6Pase (P<0.01) expression in the lamb. Our findings highlight the sensitivity of the epigenome to maternal nutrition around conception and the need for dietary interventions that maximize metabolic benefits and minimize metabolic costs for the next generation.

  10. Acute depletion of Tet1-dependent 5-hydroxymethylcytosine levels impairs LIF/Stat3 signaling and results in loss of embryonic stem cell identity.

    Science.gov (United States)

    Freudenberg, Johannes M; Ghosh, Swati; Lackford, Brad L; Yellaboina, Sailu; Zheng, Xiaofeng; Li, Ruifang; Cuddapah, Suresh; Wade, Paul A; Hu, Guang; Jothi, Raja

    2012-04-01

    The TET family of FE(II) and 2-oxoglutarate-dependent enzymes (Tet1/2/3) promote DNA demethylation by converting 5-methylcytosine to 5-hydroxymethylcytosine (5hmC), which they further oxidize into 5-formylcytosine and 5-carboxylcytosine. Tet1 is robustly expressed in mouse embryonic stem cells (mESCs) and has been implicated in mESC maintenance. Here we demonstrate that, unlike genetic deletion, RNAi-mediated depletion of Tet1 in mESCs led to a significant reduction in 5hmC and loss of mESC identity. The differentiation phenotype due to Tet1 depletion positively correlated with the extent of 5hmC loss. Meta-analyses of genomic data sets suggested interaction between Tet1 and leukemia inhibitory factor (LIF) signaling. LIF signaling is known to promote self-renewal and pluripotency in mESCs partly by opposing MAPK/ERK-mediated differentiation. Withdrawal of LIF leads to differentiation of mESCs. We discovered that Tet1 depletion impaired LIF-dependent Stat3-mediated gene activation by affecting Stat3's ability to bind to its target sites on chromatin. Nanog overexpression or inhibition of MAPK/ERK signaling, both known to maintain mESCs in the absence of LIF, rescued Tet1 depletion, further supporting the dependence of LIF/Stat3 signaling on Tet1. These data support the conclusion that analysis of mESCs in the hours/days immediately following efficient Tet1 depletion reveals Tet1's normal physiological role in maintaining the pluripotent state that may be subject to homeostatic compensation in genetic models.

  11. High-Frequency Signal Injection Method Based on Duty Cycle Shifting Without Maximum Fundamental Voltage Magnitude Loss

    DEFF Research Database (Denmark)

    Wang, Dong; Lu, Kaiyuan; Rasmussen, Peter Omand

    2017-01-01

    position estimation algorithm using the proposed HFSI method is developed and applied to a synchronous reluctance machine drive system. The proposed algorithm focuses on the medium- to high-speed range with the advantage of no filter needed for position information extraction and a machine......-frequency signal at half of the switching frequency without the necessity to sacrifice the machine fundamental voltage amplitude. This may be utilized to develop a new position estimation algorithm without involving the machine inductance in the medium- to high-speed range. As an application example, a new...

  12. New Nordic Diet-Induced Weight Loss Is Accompanied by Changes in Metabolism and AMPK Signaling in Adipose Tissue.

    Science.gov (United States)

    Fritzen, Andreas Mæchel; Lundsgaard, Anne-Marie; Jordy, Andreas Børsting; Poulsen, Sanne Kellebjerg; Stender, Steen; Pilegaard, Henriette; Astrup, Arne; Larsen, Thomas Meinert; Wojtaszewski, Jørgen F P; Richter, Erik A; Kiens, Bente

    2015-09-01

    The molecular mechanisms behind diet-induced metabolic improvements remain to be studied. This study sought to investigate whether expression of proteins in skeletal muscle or adipose tissue could explain improvements in glucose and lipid homeostasis after weight loss. Volunteers consumed a New Nordic Diet (NND) or an Average Danish Diet for 26 weeks in a controlled, free-living setting. Sixty four moderately obese women and men (44 ± 2 y; body mass index, 31 ± 1 kg/m(2)). Fasting blood samples and biopsies from the vastus lateralis muscle and subcutaneous abdominal adipose tissue (SCAT) were obtained at week 0 and 26. Gene and protein expressions were analyzed by real-time PCR and Western blotting. Improved homeostasis homeostatic model of assessment-insulin resistance index and lowered plasma triacylglycerol concentration after NND coincided with molecular adaptations in SCAT but not in skeletal muscle. NND induced greater reduction in fat mass than ADD (-6 ± 1 kg and -2 ± 1 kg; P weight loss.

  13. Injury Signals Cooperate with Nf1 Loss to Relieve the Tumor-Suppressive Environment of Adult Peripheral Nerve

    Directory of Open Access Journals (Sweden)

    Sara Ribeiro

    2013-10-01

    Full Text Available Schwann cells are highly plastic cells that dedifferentiate to a progenitor-like state following injury. However, deregulation of this plasticity, may be involved in the formation of neurofibromas, mixed-cell tumors of Schwann cell (SC origin that arise upon loss of NF1. Here, we show that adult myelinating SCs (mSCs are refractory to Nf1 loss. However, in the context of injury, Nf1-deficient cells display opposing behaviors along the wounded nerve; distal to the injury, Nf1−/− mSCs redifferentiate normally, whereas at the wound site Nf1−/− mSCs give rise to neurofibromas in both Nf1+/+ and Nf1+/− backgrounds. Tracing experiments showed that distinct cell types within the tumor derive from Nf1-deficient SCs. This model of neurofibroma formation demonstrates that neurofibromas can originate from adult SCs and that the nerve environment can switch from tumor suppressive to tumor promoting at a site of injury. These findings have implications for both the characterization and treatment of neurofibromas.

  14. Loss of WISP-2/CCN5 signaling in human pancreatic cancer: a potential mechanism for epithelial-mesenchymal-transition.

    Science.gov (United States)

    Dhar, Gopal; Mehta, Smita; Banerjee, Snigdha; Gardner, Ashleigh; McCarty, Bryan M; Mathur, Sharad C; Campbell, Donald R; Kambhampati, Suman; Banerjee, Sushanta K

    2007-08-28

    The objective of this study was to explore the pathophysiological relevance of WISP-2/CCN5 in progression of human pancreatic adenocarcinoma (PAC). We found WISP-2/CCN5 mRNA and protein expression was faint and sporadic in PAC and detected in only 8.7-20% of the samples with varying grades as compared to adjacent normal and chronic pancreatitis samples where expression was very high in the ducts and acini. Colocalization studies in tissue-microarray slides revealed WISP-2/CCN5 mRNA loss was associated with p53 overexpression in PAC. Like tissue samples, p53 mutant-PAC cell lines show loss of WISP-2/CCN5. Moreover, functional analysis studies demonstrate exposure of pancreatic cancer cells to WISP-2/CCN5 recombinant protein enhances mesenchymal-epithelial-transition (MET). Collectively, we suggest WISP-2/CCN5 silencing may be a critical event during differentiation and progression of PAC and mutant p53 is possibly an important player in pursuing this episode.

  15. NPs/NPRs Signaling Pathways May Be Involved in Depression-Induced Loss of Gastric ICC by Decreasing the Production of mSCF.

    Directory of Open Access Journals (Sweden)

    Xue-Lian Lin

    Full Text Available It is well known that natriuretic peptides (NPs are involved in the regulation of gastrointestinal motility. Interstitial cells of Cajal (ICC are the pacemaker cells of gastrointestinal motility and gastrointestinal dyskinesia is one of the important digestive tract symptoms of depression. However, it is unclear whether they are involved in depression-induced loss of ICC. The aim of the present study was to investigate the relationship between the natriuretic peptide signaling pathway and depression-induced loss of gastric ICC in depressed rats. These results showed that the expression of c-kit and stem cell factor (SCF in smooth muscle layers of stomach were down-regulated in depressed rats at the mRNA and protein levels. The expression of natriuretic peptide receptor (NPR-A, B and C were up-regulated in the stomach of depressed rats at the mRNA and protein levels. NPR-A, B and C can significantly decrease the expression of SCF to treat cultured gastric smooth muscle cells (GSMCs obtained from normal rats with different concentrations of C-type natriuretic peptide (CNP. Pretreatment of cultured GSMCs with 8-Brom-cGMP (8-Br-cGMP, a membrane permeable cGMP analog, cANF (a specific NPR-C agonist and CNP (10-6 mol/L demonstrated that 8-Br-cGMP had a similar effect as CNP, but treatment with cANF did not. The results of the methyl thiazolyl tetrazolium bromide (MTT assay indicated that high concentrations of cANF (10-6 mol/L restrained the proliferation of cultured GSMCs. Taken together, these results indicate that the up-regulation of the NPs/NPR-C and NPs/NPR-A, B/cGMP signaling pathways may be involved in depression-induced loss of gastric ICC.

  16. Loss of the AE3 Cl-/HCO3- exchanger in mice affects rate-dependent inotropy and stress-related AKT signaling in heart

    Directory of Open Access Journals (Sweden)

    Vikram ePrasad

    2013-12-01

    Full Text Available Cl-/HCO3- exchangers are expressed abundantly in cardiac muscle, suggesting that HCO3- extrusion serves an important function in heart. Mice lacking Anion Exchanger Isoform 3 (AE3, a major cardiac Cl-/HCO3- exchanger, appear healthy, but loss of AE3 causes decompensation in a hypertrophic cardiomyopathy (HCM model. Using intra-ventricular pressure analysis, in vivo pacing, and molecular studies we identified physiological and biochemical changes caused by loss of AE3 that may contribute to decompensation in HCM. AE3-null mice had normal cardiac contractility under basal conditions and after -adrenergic stimulation, but pacing of hearts revealed that frequency-dependent inotropy was blunted, suggesting that AE3-mediated HCO3- extrusion is required for a robust force-frequency response (FFR during acute biomechanical stress in vivo. Modest changes in expression of proteins that affect Ca2+-handling were observed, but Ca2+-transient analysis of AE3-null myocytes showed normal twitch-amplitude and Ca2+-clearance. Phosphorylation and expression of several proteins implicated in HCM and FFR, including phospholamban, myosin binding protein C, and troponin I were not altered in hearts of paced AE3-null mice; however, phosphorylation of Akt, which plays a central role in mechanosensory signaling, was significantly higher in paced AE3-null hearts than in wild-type controls and phosphorylation of AMPK, which is affected by Akt and is involved in energy metabolism and some cases of HCM, was reduced. These data show loss of AE3 leads to impaired rate-dependent inotropy, appears to affect mechanical stress-responsive signaling, and reduces activation of AMPK, which may contribute to decompensation in heart failure.

  17. Sequential signaling cascade of IL-6 and PGC-1α is involved in high glucose-induced podocyte loss and growth arrest

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Dong Il; Park, Soo Hyun, E-mail: parksh@chonnam.ac.kr

    2013-06-14

    Highlights: •The pathophysiological role of IL-6 in high glucose-induced podocyte loss. •The novel role of PGC-1α in the development of diabetic nephropathy. •Signaling of IL-6 and PGC-1α in high glucose-induced dysfunction of podocyte. -- Abstract: Podocyte loss, which is mediated by podocyte apoptosis, is implicated in the onset of diabetic nephropathy. In this study, we investigated the involvement of interleukin (IL)-6 in high glucose-induced apoptosis of rat podocytes. We also examined the pathophysiological role of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) in this system. High glucose treatment induced not only podocyte apoptosis but also podocyte growth arrest. High glucose treatment also increased IL-6 secretion and activated IL-6 signaling. The high glucose-induced podocyte apoptosis was blocked by IL-6 neutralizing antibody. IL-6 treatment or overexpression induced podocyte apoptosis and growth arrest, and IL-6 siRNA transfection blocked high glucose-induced podocyte apoptosis and growth arrest. Furthermore, high glucose or IL-6 treatment increased PGC-1α expression, and PGC-1α overexpression also induced podocyte apoptosis and growth arrest. PGC-1α siRNA transfection blocked high glucose-induced podocyte apoptosis and growth arrest. Collectively, these findings showed that high glucose promoted apoptosis and cell growth arrest in podocytes via IL-6 signaling. In addition, PGC-1α is involved in podocyte apoptosis and cell growth arrest. Therefore, blocking IL-6 and its downstream mediators such as IL6Rα, gp130 and PGC-1α may attenuate the progression of diabetic nephropathy.

  18. Loss of Host Type-I IFN Signaling Accelerates Metastasis and Impairs NK-cell Antitumor Function in Multiple Models of Breast Cancer.

    Science.gov (United States)

    Rautela, Jai; Baschuk, Nikola; Slaney, Clare Y; Jayatilleke, Krishnath M; Xiao, Kun; Bidwell, Bradley N; Lucas, Erin C; Hawkins, Edwin D; Lock, Peter; Wong, Christina S; Chen, Weisan; Anderson, Robin L; Hertzog, Paul J; Andrews, Daniel M; Möller, Andreas; Parker, Belinda S

    2015-11-01

    Metastatic progression is the major cause of breast cancer-related mortality. By examining multiple syngeneic preclinical breast cancer models in mice lacking a functional type-I interferon receptor (Ifnar1(-/-) mice), we show that host-derived type-I interferon (IFN) signaling is a critical determinant of metastatic spread that is independent of primary tumor growth. In particular, we show that bone metastasis can be accelerated in Balb/c Ifnar1(-/-) mice bearing either 4T1 or 66cl4 orthotopic tumors and, for the first time, present data showing the development of bone metastasis in the C57Bl/6 spontaneous MMTV-PyMT-driven model of tumorigenesis. Further exploration of these results revealed that endogenous type-I IFN signaling to the host hematopoietic system is a key determinant of metastasis-free survival and critical to the responsiveness of the circulating natural killer (NK)-cell population. We find that in vivo-stimulated NK cells derived from wild-type, but not Ifnar1(-/-), mice can eliminate the 4T1 and 66cl4 breast tumor lines with varying kinetics in vitro. Together, this study indicates that the dysregulated immunity resulting from a loss of host type-I IFN signaling is sufficient to drive metastasis, and provides a rationale for targeting the endogenous type-I IFN pathway as an antimetastatic strategy. ©2015 American Association for Cancer Research.

  19. Loss of canonical Smad4 signaling promotes KRAS driven malignant transformation of human pancreatic duct epithelial cells and metastasis.

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    Lisa Leung

    Full Text Available Pancreatic ductal adenocarcinoma (PDAC is the fourth most common cause of cancer death in North America. Activating KRAS mutations and Smad4 loss occur in approximately 90% and 55% of PDAC, respectively. While their roles in the early stages of PDAC development have been confirmed in genetically modified mouse models, their roles in the multistep malignant transformation of human pancreatic duct cells have not been directly demonstrated. Here, we report that Smad4 represents a barrier in KRAS-mediated malignant transformation of the near normal immortalized human pancreatic duct epithelial (HPDE cell line model. Marked Smad4 downregulation by shRNA in KRAS (G12V expressing HPDE cells failed to cause tumorigenic transformation. However, KRAS-mediated malignant transformation occurred in a new HPDE-TGF-β resistant (TβR cell line that completely lacks Smad4 protein expression and is resistant to the mito-inhibitory activity of TGF-β. This transformation resulted in tumor formation and development of metastatic phenotype when the cells were implanted orthotopically into the mouse pancreas. Smad4 restoration re-established TGF-β sensitivity, markedly increased tumor latency by promoting apoptosis, and decreased metastatic potential. These results directly establish the critical combination of the KRAS oncogene and complete Smad4 inactivation in the multi-stage malignant transformation and metastatic progression of normal human HPDE cells.

  20. Loss of TGF-β signaling in osteoblasts increases basic-FGF and promotes prostate cancer bone metastasis.

    Science.gov (United States)

    Meng, Xiangqi; Vander Ark, Alexandra; Daft, Paul; Woodford, Erica; Wang, Jie; Madaj, Zachary; Li, Xiaohong

    2018-04-01

    TGF-β plays a central role in prostate cancer (PCa) bone metastasis, and it is crucial to understand the bone cell-specific role of TGF-β signaling in this process. Thus, we used knockout (KO) mouse models having deletion of the Tgfbr2 gene specifically in osteoblasts (Tgfbr2 Col1CreERT KO) or in osteoclasts (Tgfbr2 LysMCre KO). We found that PCa-induced bone lesion development was promoted in the Tgfbr2 Col1CreERT KO mice, but was inhibited in the Tgfbr2 LysMCre KO mice, relative to their respective control Tgfbr2 FloxE2 littermates. Since metastatic PCa cells attach to osteoblasts when colonized in the bone microenvironment, we focused on the mechanistic studies using the Tgfbr2 Col1CreERT KO mouse model. We found that bFGF was upregulated in osteoblasts from PC3-injected tibiae of Tgfbr2 Col1CreERT KO mice and correlated with increased tumor cell proliferation, angiogenesis, amounts of cancer-associated fibroblasts and osteoclasts. In vitro studies showed that osteoblastogenesis was inhibited, osteoclastogenesis was stimulated, but PC3 viability was not affected, by bFGF treatments. Lastly, the increased PC3-induced bone lesions in Tgfbr2 Col1CreERT KO mice were significantly attenuated by blocking bFGF using neutralizing antibody, suggesting bFGF is a promising target inhibiting bone metastasis. Copyright © 2018 Elsevier B.V. All rights reserved.

  1. Osteoblast-Specific Loss of IGF1R Signaling Results in Impaired Endochondral Bone Formation During Fracture Healing

    Science.gov (United States)

    Wang, Tao; Wang, Yongmei; Menendez, Alicia; Fong, Chak; Babey, Muriel; Tahimic, Candice GT; Cheng, Zhiqiang; Li, Alfred; Chang, Wenhan; Bikle, Daniel D.

    2017-01-01

    Insulin-like growth factors (IGFs) are important local regulators during fracture healing. Although IGF1 deficiency is known to increase the risk of delayed union or non-union fractures in the elderly population, the underlying mechanisms that contribute to this defect remains unclear. In this study, IGF1 signaling during fracture healing was investigated in an osteoblast-specific IGF1 receptor (IGF1R) conditional knockout (KO) mouse model. A closed tibial fracture was induced in IGF1Rflox/flox/2.3-kb α1(1)-collagen-Cre (KO) and IGF1Rflox/flox (control) mice aged 12 weeks. Fracture callus samples and nonfractured tibial diaphysis were collected and analyzed by μCT, histology, immunohistochemistry, histomorphometry, and gene expression analysis at 10, 15, 21, and 28 days after fracture. A smaller size callus, lower bone volume accompanied by a defect in mineralization, bone microarchitectural abnormalities, and a higher cartilage volume were observed in the callus of these KO mice. The levels of osteoblast differentiation markers (osteocalcin, alkaline phosphatase, collagen 1α1) were significantly reduced, but the early osteoblast transcription factor runx2, as well as chondrocyte differentiation markers (collagen 2α1 and collagen 10α1) were significantly increased in the KO callus. Moreover, increased numbers of osteoclasts and impaired angiogenesis were observed during the first 15 days of fracture repair, but decreased numbers of osteoclasts were found in the later stages of fracture repair in the KO mice. Although baseline nonfractured tibias of KO mice had decreased trabecular and cortical bone compared to control mice, subsequent studies with mice expressing the 2.3-kb α1(1)-collagen-Cre ERT2 construct and given tamoxifen at the time of fracture and so starting with comparable bone levels showed similar impairment in fracture repair at least initially. Our data indicate that not only is the IGF1R in osteoblasts involved in osteoblast differentiation

  2. Salvia plebeia R.Br. inhibits signal transduction of IL-6 and prevents ovariectomy-induced bone loss by suppressing osteoclastogenesis.

    Science.gov (United States)

    Kim, Mi-Hwa; Jung, Kyungsook; Nam, Ki-Hoan; Jang, Hyun-Jae; Lee, Seung Woong; Kim, Yesol; Park, Chan Sun; Lee, Tae-Hoon; Park, Jee Hun; Choi, Jung Ho; Rho, Mun-Chual; Oh, Hyun-Mee

    2016-12-01

    The interleukin-6 (IL-6) family of cytokines plays a key role in the pathogenesis of rheumatoid arthritis and osteoporosis through the regulation of bone formation and resorption. In this study, it was observed that ethanol extract of Salvia plebeia R.Br. (S.P-EE) inhibited IL-6-induced signaling cascade including phosphorylation of JAK2/STAT3 and ERK. Subsequently, it was examined whether S.P-EE treatment could recover bone loss in ovariectomized (OVX) mice. Indeed, S.P-EE exhibited both preventive and therapeutic effect on OVX-induced bone loss in trabecular microarchitecture along with significant increase in bone mineral density and content. To understand the mechanism of action of S.P-EE in bone metabolism, the effect of S.P-EE on osteoclast differentiation and activity was investigated. S.P-EE significantly inhibited RANKL-induced osteoclast differentiation by suppressing phosphorylation of MAPK and Akt, and expression of NFATc1 and osteoclast marker genes. S.P-EE also inhibited bone-resorbing activity of osteoclasts. Furthermore, isolation and identification of the active compounds which are responsible for the inhibitory effect of S.P-EE on osteoclast differentiation was carried out. Six major flavonoids and plebeiolide A-C were isolated and examined their effects on osteoclast differentiation. Luteolin and hispidulin, and plebeiolide A and C, not B exhibited potent inhibitory activity on RANKL-induced osteoclast formation.

  3. Infection-stimulated Anemia Results Primarily from Interferon Gamma-dependent, Signal Transducer and Activator of Transcription 1-independent Red Cell Loss

    Directory of Open Access Journals (Sweden)

    Zheng Wang

    2015-01-01

    Full Text Available Background: Although the onset of anemia during infectious disease is commonly correlated with production of inflammatory cytokines, the mechanisms by which cytokines induce anemia are poorly defined. This study focused on the mechanism research. Methods: Different types of mice were infected perorally with Toxoplasma gondii strain ME49. At the indicated times, samples from each mouse were harvested, processed, and analyzed individually. Blood samples were analyzed using a Coulter Counter and red blood cell (RBC survival was measured by biotinylation. Levels of tumor necrosis factor-α (TNF-α, inducible nitric oxide synthase (iNOS, and inducible protein 10 (IP-10 mRNA in liver tissue were measured by real-time polymerase chain reaction. Results: T. gondii-infected mice exhibited anemia due to a decrease in both erythropoiesis and survival time of RBC in the circulation (P < 0.02. In addition, infection-stimulated anemia was associated with fecal occult, supporting previous literature that hemorrhage is a consequence of T. gondii infection in mice. Infection-induced anemia was abolished in interferon gamma (IFNγ and IFNγ receptor deficient mice (P < 0.05 but was still evident in mice lacking TNF-α, iNOS, phagocyte NADPH oxidase or IP-10 (P < 0.02. Neither signal transducer and activator of transcription 1 (STAT1 deficient mice nor 129S6 controls exhibited decreased erythropoiesis, but rather suffered from an anemia resulting solely from increased loss of circulating RBC. Conclusions: Infection-stimulated decrease in erythropoiesis and losses of RBC have distinct mechanistic bases. These results show that during T. gondii infection, IFNγ is responsible for an anemia that results from both a decrease in erythropoiesis and a STAT1 independent loss of circulating RBC.

  4. Diffuse light reflectance signals as potential indicators of loss of viability in brain tissue due to hypoxia: charge-coupled-device-based imaging and fiber-based measurement.

    Science.gov (United States)

    Kawauchi, Satoko; Nishidate, Izumi; Uozumi, Yoichi; Nawashiro, Hiroshi; Ashida, Hiroshi; Sato, Shunichi

    2013-01-01

    Brain tissue is highly vulnerable to ischemia/hypoxia, and real-time monitoring of its viability is important. By fiber-based measurements for rat brain, we previously observed a unique triphasic reflectance change (TRC) after a certain period of time after hypoxia. After TRC, rats could not be rescued, suggesting that TRC can be used as an indicator of loss of brain tissue viability. In this study, we investigated this diffuse-reflectance change due to hypoxia in three parts. First, we developed and validated a theoretical method to quantify changes in the absorption and reduced scattering coefficients involved in TRC. Second, we performed charge-coupled-device-based reflectance imaging of the rat brain during hypoxia followed by reoxygenation to examine spatiotemporal characteristics of the reflectance and its correlation with reversibility of brain tissue damage. Third, we made simultaneous imaging and fiber-based measurement of the reflectance for the rat to compare signals obtained by these two modalities. We observed a nontriphasic reflectance change by the imaging, and it was associated with brain tissue viability. We found that TRC measured by the fibers preceded the reflectance-signal change captured by the imaging. This time difference is attributable to the different observation depths in the brain with these two methods.

  5. Magnetic resonance imaging signal reduction may precede volume loss in the pituitary gland of transfusion-dependent beta-thalassemic patients

    Energy Technology Data Exchange (ETDEWEB)

    Hekmatnia, Ali; Rahmani, Ali Asghar; Adibi, Atoosa (Image Processing and Signal Research Center, Dept. of Radiology, Isfahan Univ. of Medical Sciences, Isfahan (Iran)); Radmard, Amir Reza (Dept. of Radiology, Shariati Hospital, Tehran Univ. of Medical Sciences, Tehran (Iran)); Khademi, Hooman (Shariati Hospital, Tehran Univ. of Medical Sciences, Tehran (Iran)), e-mail: radmard@ams.ac.ir

    2010-01-15

    Background: Pituitary iron overload in patients with transfusion-dependent beta-thalassemia may lead to delayed puberty. Magnetic resonance imaging (MRI) has the potential to estimate tissue iron concentration by detecting its paramagnetic effect and hypophyseal damage by measuring its dimensions indirectly. Purpose: To investigate the association of pituitary MRI findings and pubertal status in thalassemic patients as well as to demonstrate any priority in appearance of them. Material and Methods: Twenty-seven beta-thalassemic patients, aged 15-25 years, were divided into 13 with (group A) and 14 without hypogonadism (group B), matched by age, gender, duration of transfusion, and chelation therapy. Thirty-eight age- and sex-adjusted healthy control individuals were also included (group C). All participants underwent pituitary MRI using a 1.5T unit. Pituitary-to-fat signal intensity ratios (SIR) were calculated from coronal T2-weighted images. Estimated pituitary volumes were measured using pituitary height, width, and length on T1-weighted images. Results: The mean values of pituitary-to-fat SIRs were significantly lower in group A as compared with group B (P <0.001), and likewise group B had statistically lower values than group C (P=0.03). The pituitary height and volume were significantly decreased in group A compared to group B (P = 0.006 and P = 0.002, respectively), while these differences did not demonstrate statistically significance between groups B and C. Conclusion: Pituitary MRI findings such as signal intensity reduction and decrease in volume can be useful markers in estimating pituitary dysfunction in beta-thalassemic patients. Compared to healthy controls, lower values of pituitary-to-fat SIRs in thalassemic patients experiencing normal puberty, without marked decrease in volume, indicate that signal reduction may precede volume loss and could be expected first on MRI

  6. Perceptual consequences of different signal changes due to binaural noise reduction: do hearing loss and working memory capacity play a role?

    Science.gov (United States)

    Neher, Tobias; Grimm, Giso; Hohmann, Volker

    2014-01-01

    In a previous study, ) investigated whether pure-tone average (PTA) hearing loss and working memory capacity (WMC) modulate benefit from different binaural noise reduction (NR) settings. Results showed that listeners with smaller WMC preferred strong over moderate NR even at the expense of poorer speech recognition due to greater speech distortion (SD), whereas listeners with larger WMC did not. To enable a better understanding of these findings, the main aims of the present study were (1) to explore the perceptual consequences of changes to the signal mixture, target speech, and background noise caused by binaural NR, and (2) to determine whether response to these changes varies with WMC and PTA. As in the previous study, four age-matched groups of elderly listeners (with N = 10 per group) characterized by either mild or moderate PTAs and either better or worse performance on a visual measure of WMC participated. Five processing conditions were tested, which were based on the previously used (binaural coherence-based) NR scheme designed to attenuate diffuse signal components at mid to high frequencies. The five conditions differed in terms of the type of processing that was applied (no NR, strong NR, or strong NR with restoration of the long-term stimulus spectrum) and in terms of whether the target speech and background noise were processed in the same manner or whether one signal was left unprocessed while the other signal was processed with the gains computed for the signal mixture. Comparison across these conditions allowed assessing the effects of changes in high-frequency audibility (HFA), SD, and noise attenuation and distortion (NAD). Outcome measures included a dual-task paradigm combining speech recognition with a visual reaction time (VRT) task as well as ratings of perceived effort and overall preference. All measurements were carried out using headphone simulations of a frontal target speaker in a busy cafeteria. Relative to no NR, strong NR was found

  7. Loss of p12CDK2-AP1 Expression in Human Oral Squamous Cell Carcinoma with Disrupted Transforming Growth Factor-β-Smad Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Hui Peng

    2006-12-01

    Full Text Available We examined correlations between TGF-β1, TβR-I and TβR-II, p12CDK2-AP1 p21WAF1 p27KIP1 Smad2, and p-Smad2 in 125 cases of human oral squamous cell carcinoma (OSCC to test the hypothesis that resistance to TGF-β1-induced growth suppression is due to the disruption of its signaling pathway as a consequence of reduced or lost p12CDK2-AP1. Immunoreactivity for TβR-II decreased in OSCC with increasing disease aggressiveness; however, no differences were observed for TβR-I and TGF-β1. The expression of TβR-II significantly correlated with p12CDK2-AP1 and p27KIP1 (P<.001 and P<.01, respectively. Furthermore, there was a significant relationship between TβR-II expression and p-Smad2 (P < .001. The in vivo correlation of the levels of TβR-II, p12CDK2-AP1 and p27 KIP1 was confirmed in normal and OSCC cell lines. Additionally, in vitro analysis of TGF-β-treated cells showed that TGF-β1 treatment of normal keratinocytes suppressed cell growth with upregulation of p-Smad2, p12CDK2-API and p21WAF1 expression, whereas there was no effect on OSCC cell lines. These results provide evidence of a link between a disrupted TGF-β-Smad signaling pathway and loss of induction of cell cycle-inhibitory proteins, especially p12CDK2-AP1 in OSCC, which may lead to the resistance of TGF-β1 growth-inhibitory effect on OSCC.

  8. Stromal liver kinase B1 [STK11] signaling loss induces oviductal adenomas and endometrial cancer by activating mammalian Target of Rapamycin Complex 1.

    Directory of Open Access Journals (Sweden)

    Pradeep S Tanwar

    Full Text Available Germline mutations of the Liver Kinase b1 (LKB1/STK11 tumor suppressor gene have been linked to Peutz-Jeghers Syndrome (PJS, an autosomal-dominant, cancer-prone disorder in which patients develop neoplasms in several organs, including the oviduct, ovary, and cervix. We have conditionally deleted Lkb1 in Müllerian duct mesenchyme-derived cells of the female reproductive tract and observed expansion of the stromal compartment and hyperplasia and/or neoplasia of adjacent epithelial cells throughout the reproductive tract with paratubal cysts and adenomyomas in oviducts and, eventually, endometrial cancer. Examination of the proliferation marker phospho-histone H3 and mammalian Target Of Rapamycin Complex 1 (mTORC1 pathway members revealed increased proliferation and mTORC1 activation in stromal cells of both the oviduct and uterus. Treatment with rapamycin, an inhibitor of mTORC1 activity, decreased tumor burden in adult Lkb1 mutant mice. Deletion of the genes for Tuberous Sclerosis 1 (Tsc1 or Tsc2, regulators of mTORC1 that are downstream of LKB1 signaling, in the oviductal and uterine stroma phenocopies some of the defects observed in Lkb1 mutant mice, confirming that dysregulated mTORC1 activation in the Lkb1-deleted stroma contributes to the phenotype. Loss of PTEN, an upstream regulator of mTORC1 signaling, along with Lkb1 deletion significantly increased tumor burden in uteri and induced tumorigenesis in the cervix and vagina. These studies show that LKB1/TSC1/TSC2/mTORC1 signaling in mesenchymal cells is important for the maintenance of epithelial integrity and suppression of carcinogenesis in adjacent epithelial cells. Because similar changes in the stromal population are also observed in human oviductal/ovarian adenoma and endometrial adenocarcinoma patients, we predict that dysregulated mTORC1 activity by upstream mechanisms similar to those described in these model systems contributes to the pathogenesis of these human diseases.

  9. Monte Carlo Studies of the Radiation Fields in the Linac Coherent Light Source Undulators and of the Corresponding Signals in the Cerenkov Beam Loss Monitors

    Energy Technology Data Exchange (ETDEWEB)

    Santana Leitner, Mario; Fasso, Alberto; Fisher, Alan S.; Nuhn, Heinz D.; /SLAC; Dooling, Jeffrey C.; Berg, William; Yang, Bin X.; /Argonne

    2010-09-14

    In 2009 the Linac Coherent Light Source (LCLS) at the SLAC National Accelerator Center started free electron laser (FEL) operation. In order to continue to produce the bright and short-pulsed x-ray laser demanded by FEL scientists, this pioneer hard x-ray FEL requires a perfectly tailored magnetic field at the undulators, so that the photons generated at the electron wiggling path interact at the right phase with the electron beam. In such a precise system, small (>0.01%) radiation-induced alterations of the magnetic field in the permanent magnets could affect FEL performance. This paper describes the simulation studies of radiation fields in permanent magnets and the expected signal in the detectors. The transport of particles from the radiation sources (i.e. diagnostic insert) to the undulator magnets and to the beam loss monitors (BLM) was simulated with the intra nuclear cascade codes FLUKA and MARS15. In order to accurately reproduce the optics of LCLS, lattice capabilities and magnetic fields were enabled in FLUKA and betatron oscillations were validated against reference data. All electron events entering the BLMs were printed in data files. The paper also introduces the Radioactive Ion Beam Optimizer (RIBO) Monte Carlo 3-D code, which was used to read from the event files, to compute Cerenkov production and then to simulate the optical coupling of the BLM detectors, accounting for the transmission of light through the quartz.

  10. Comparison of Speech-in-Noise and Localization Benefits in Unilateral Hearing Loss Subjects Using Contralateral Routing of Signal Hearing Aids or Bone-Anchored Implants.

    Science.gov (United States)

    Snapp, Hillary A; Holt, Fred D; Liu, Xuezhong; Rajguru, Suhrud M

    2017-01-01

    To compare the benefit of wireless contralateral routing of signal (CROS) technology to bone-anchored implant (BAI) technology in monaural listeners. Prospective, single-subject. Tertiary academic referral center. Adult English speaking subjects using either a CROS hearing aid or BAI as treatment for unilateral severe-profound hearing loss. Aided performance utilizing the subjects BAI or CROS hearing device. Outcome measures included speech-in-noise perception using the QuickSIN (Etymotic Research, Elkgrove Village, IL, 2001) speech-in-noise test and localization ability using narrow and broadband stimuli. Performance was measured in the unaided and aided condition and compared with normal hearing controls. Subjective outcomes measures included the Speech Spatial and Qualities hearing scale and the Glasgow Hearing Aid Benefit Profile. A significant improvement in speech-in-noise performance for monaural listeners (p noise performance. CROS and BAI hearing devices do not provide any localization benefit in the horizontal plane for monaural listeners and there is no significant difference between systems.

  11. Genomic loss of tumor suppressor miRNA-204 promotes cancer cell migration and invasion by activating AKT/mTOR/Rac1 signaling and actin reorganization.

    Directory of Open Access Journals (Sweden)

    J Saadi Imam

    Full Text Available Increasing evidence suggests that chromosomal regions containing microRNAs are functionally important in cancers. Here, we show that genomic loci encoding miR-204 are frequently lost in multiple cancers, including ovarian cancers, pediatric renal tumors, and breast cancers. MiR-204 shows drastically reduced expression in several cancers and acts as a potent tumor suppressor, inhibiting tumor metastasis in vivo when systemically delivered. We demonstrated that miR-204 exerts its function by targeting genes involved in tumorigenesis including brain-derived neurotrophic factor (BDNF, a neurotrophin family member which is known to promote tumor angiogenesis and invasiveness. Analysis of primary tumors shows that increased expression of BDNF or its receptor tropomyosin-related kinase B (TrkB parallel a markedly reduced expression of miR-204. Our results reveal that loss of miR-204 results in BDNF overexpression and subsequent activation of the small GTPase Rac1 and actin reorganization through the AKT/mTOR signaling pathway leading to cancer cell migration and invasion. These results suggest that microdeletion of genomic loci containing miR-204 is directly linked with the deregulation of key oncogenic pathways that provide crucial stimulus for tumor growth and metastasis. Our findings provide a strong rationale for manipulating miR-204 levels therapeutically to suppress tumor metastasis.

  12. An alternative method to amplify RNA without loss of signal conservation for expression analysis with a proteinase DNA microarray in the ArrayTube® format

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    Wiederanders B

    2006-06-01

    Full Text Available Abstract Background Recent developments in DNA microarray technology led to a variety of open and closed devices and systems including high and low density microarrays for high-throughput screening applications as well as microarrays of lower density for specific diagnostic purposes. Beside predefined microarrays for specific applications manufacturers offer the production of custom-designed microarrays adapted to customers' wishes. Array based assays demand complex procedures including several steps for sample preparation (RNA extraction, amplification and sample labelling, hybridization and detection, thus leading to a high variability between several approaches and resulting in the necessity of extensive standardization and normalization procedures. Results In the present work a custom designed human proteinase DNA microarray of lower density in ArrayTube® format was established. This highly economic open platform only requires standard laboratory equipment and allows the study of the molecular regulation of cell behaviour by proteinases. We established a procedure for sample preparation and hybridization and verified the array based gene expression profile by quantitative real-time PCR (QRT-PCR. Moreover, we compared the results with the well established Affymetrix microarray. By application of standard labelling procedures with e.g. Klenow fragment exo-, single primer amplification (SPA or In Vitro Transcription (IVT we noticed a loss of signal conservation for some genes. To overcome this problem we developed a protocol in accordance with the SPA protocol, in which we included target specific primers designed individually for each spotted oligomer. Here we present a complete array based assay in which only the specific transcripts of interest are amplified in parallel and in a linear manner. The array represents a proof of principle which can be adapted to other species as well. Conclusion As the designed protocol for amplifying m

  13. MTOR signaling and ubiquitin-proteosome gene expression in the preservation of fat free mass following high protein, calorie restricted weight loss

    OpenAIRE

    McIver Cassandra M; Wycherley Thomas P; Clifton Peter M

    2012-01-01

    Abstract Caloric restriction is one of the most efficient ways to promote weight loss and is known to activate protective metabolic pathways. Frequently reported with weight loss is the undesirable consequence of fat free (lean muscle) mass loss. Weight loss diets with increased dietary protein intake are popular and may provide additional benefits through preservation of fat free mass compared to a standard protein, high carbohydrate diet. However, the precise mechanism by which a high prote...

  14. Constitutive loss and acute pharmacological manipulation of ErbB4 signaling do not affect attention and inhibitory control in mice.

    Science.gov (United States)

    Marchisella, E; Wijnands, R; Koopmans, B; Spijker, S; Loos, M

    2017-08-09

    The receptor tyrosine kinase ErbB4 and its ligand trophic factors of the neuregulin (NRG) family have been associated with schizophrenia and other mental disorders in human genetic studies. In vivo studies in mice have shown how abnormal Nrg-ErbB4 signaling leads to deviant behaviors relevant to distinct aspects of schizophrenia, including hyperactivity, sensory gating deficits, working and spatial memory deficits and impaired social behavior. However, so far little is known on the role of ErbB4 in attention and inhibitory control, two aspects of executive functions that are impaired in schizophrenia. Here we investigated the effects of constitutive loss of ErbB4 in the central nervous system of mice on performance in a 5-choice serial reaction time task (5CSRTT) assessing attention and inhibitory control. In this task, ErbB4-/- mice did not show deficits in various parameters of attention, and premature responses as measure of inhibitory control. Nonetheless, ErbB4-/- mice recapitulated a specific set of behavioral phenotypes associated with schizophrenia, including a deficit in spatial learning and memory in the Barnes Maze and in contextual fear learning, and a trend for a deficit in sensorimotor gating. Furthermore, we investigated the effect of acute pharmacological inhibition of ErbB tyrosine kinase receptor using the pan-ErbB kinase inhibitor JNJ-28871063 (JNJ), in an automated version of the 5CSRTT. JNJ did not affect attention and inhibitory control. In conclusion, our data suggest no direct involvement of a classical Nrg-ErbB4 pathway in attention and inhibitory control in mice, while it confirms the involvement of this pathway in other domains relevant to schizophrenia. © 2017 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

  15. Differential effects of exposure to maternal obesity or maternal weight loss during the periconceptional period in the sheep on insulin signalling molecules in skeletal muscle of the offspring at 4 months of age.

    Directory of Open Access Journals (Sweden)

    Lisa M Nicholas

    Full Text Available Exposure to maternal obesity before and/or throughout pregnancy may increase the risk of obesity and insulin resistance in the offspring in childhood and adult life, therefore, resulting in its transmission into subsequent generations. We have previously shown that exposure to maternal obesity around the time of conception alone resulted in increased adiposity in female lambs. Changes in the abundance of insulin signalling molecules in skeletal muscle and adipose tissue precede the development of insulin resistance and type 2 diabetes. It is not clear, however, whether exposure to maternal obesity results in insulin resistance in her offspring as a consequence of the impact of increased adiposity on skeletal muscle or as a consequence of the programming of specific changes in the abundance of insulin signalling molecules in this tissue. We have used an embryo transfer model in the sheep to investigate the effects of exposure to either maternal obesity or to weight loss in normal and obese mothers preceding and for one week after conception on the expression and abundance of insulin signalling molecules in muscle in the offspring. We found that exposure to maternal obesity resulted in lower muscle GLUT-4 and Ser 9 phospho-GSK3α and higher muscle GSK3α abundance in lambs when compared to lambs conceived in normally nourished ewes. Exposure to maternal weight loss in normal or obese mothers, however, resulted in lower muscle IRS1, PI3K, p110β, aPKCζ, Thr 642 phospho-AS160 and GLUT-4 abundance in the offspring. In conclusion, maternal obesity or weight loss around conception have each programmed specific changes on subsets of molecules in the insulin signalling, glucose transport and glycogen synthesis pathways in offspring. There is a need for a stronger evidence base to ensure that weight loss regimes in obese women seeking to become pregnant minimize the metabolic costs for the next generation.

  16. Inhibition of H3K9me2 Reduces Hair Cell Regeneration after Hair Cell Loss in the Zebrafish Lateral Line by Down-Regulating the Wnt and Fgf Signaling Pathways.

    Science.gov (United States)

    Tang, Dongmei; Lin, Qin; He, Yingzi; Chai, Renjie; Li, Huawei

    2016-01-01

    The activation of neuromast (NM) supporting cell (SC) proliferation leads to hair cell (HC) regeneration in the zebrafish lateral line. Epigenetic mechanisms have been reported that regulate HC regeneration in the zebrafish lateral line, but the role of H3K9me2 in HC regeneration after HC loss remains poorly understood. In this study, we focused on the role of H3K9me2 in HC regeneration following neomycin-induced HC loss. To investigate the effects of H3K9me2 in HC regeneration, we took advantage of the G9a/GLP-specific inhibitor BIX01294 that significantly reduces the dimethylation of H3K9. We found that BIX01294 significantly reduced HC regeneration after neomycin-induced HC loss in the zebrafish lateral line. BIX01294 also significantly reduced the proliferation of NM cells and led to fewer SCs in the lateral line. In situ hybridization showed that BIX01294 significantly down-regulated the Wnt and Fgf signaling pathways, which resulted in reduced SC proliferation and HC regeneration in the NMs of the lateral line. Altogether, our results suggest that down-regulation of H3K9me2 significantly decreases HC regeneration after neomycin-induced HC loss through inactivation of the Wnt/β-catenin and Fgf signaling pathways. Thus H3K9me2 plays a critical role in HC regeneration.

  17. Inhibition of H3K9me2 Reduces Hair Cell Regeneration after Hair Cell Loss in the Zebrafish Lateral Line by Down-Regulating the Wnt and Fgf Signaling Pathways

    Directory of Open Access Journals (Sweden)

    Dongmei eTang

    2016-05-01

    Full Text Available The activation of neuromast supporting cell (SC proliferation leads to hair cell (HC regeneration in the zebrafish lateral line. Epigenetic mechanisms have been reported that regulate HC regeneration in the zebrafish lateral line, but the role of H3K9me2 in HC regeneration after HC loss remains poorly understood. In this study, we focused on the role of H3K9me2 in HC regeneration following neomycin-induced HC loss. To investigate the effects of H3K9me2 in HC regeneration, we took advantage of the G9a/GLP-specific inhibitor BIX01294 that significantly reduces the dimethylation of H3K9. We found that BIX01294 significantly reduced HC regeneration after neomycin-induced HC loss in the zebrafish lateral line. BIX01294 also significantly reduced the proliferation of neuromast cells and led to fewer SCs in the lateral line. In situ hybridization showed that BIX01294 significantly down-regulated the Wnt and Fgf signaling pathways, which resulted in reduced SC proliferation and HC regeneration in the neuromasts of the lateral line. Altogether, our results suggest that down-regulation of H3K9me2 significantly decreases HC regeneration after neomycin-induced HC loss through inactivation of the Wnt/β-catenin and Fgf signaling pathways. Thus H3K9me2 plays a critical role in HC regeneration.

  18. Hearing loss

    Science.gov (United States)

    Decreased hearing; Deafness; Loss of hearing; Conductive hearing loss; Sensorineural hearing loss; Presbycusis ... Symptoms of hearing loss may include: Certain sounds seeming too loud Difficulty following conversations when two or more people are talking ...

  19. Infection-stimulated anemia results primarily from interferon gamma-dependent, signal transducer and activator of transcription 1-independent red cell loss.

    Science.gov (United States)

    Wang, Zheng; Zhang, Dong-Xia; Zhao, Qi

    2015-04-05

    Although the onset of anemia during infectious disease is commonly correlated with production of inflammatory cytokines, the mechanisms by which cytokines induce anemia are poorly defined. This study focused on the mechanism research. Different types of mice were infected perorally with Toxoplasma gondii strain ME49. At the indicated times, samples from each mouse were harvested, processed, and analyzed individually. Blood samples were analyzed using a Coulter Counter and red blood cell (RBC) survival was measured by biotinylation. Levels of tumor necrosis factor-α (TNF-α), inducible nitric oxide synthase (iNOS), and inducible protein 10 (IP-10) mRNA in liver tissue were measured by real-time polymerase chain reaction. T. gondii-infected mice exhibited anemia due to a decrease in both erythropoiesis and survival time of RBC in the circulation (P anemia was associated with fecal occult, supporting previous literature that hemorrhage is a consequence of T. gondii infection in mice. Infection-induced anemia was abolished in interferon gamma (IFNγ) and IFNγ receptor deficient mice (P anemia resulting solely from increased loss of circulating RBC. Infection-stimulated decrease in erythropoiesis and losses of RBC have distinct mechanistic bases. These results show that during T. gondii infection, IFNγ is responsible for an anemia that results from both a decrease in erythropoiesis and a STAT1 independent loss of circulating RBC.

  20. Dahuang Zexie Decoction Protects against High-Fat Diet-Induced NAFLD by Modulating Gut Microbiota-Mediated Toll-Like Receptor 4 Signaling Activation and Loss of Intestinal Barrier

    Directory of Open Access Journals (Sweden)

    Jing Fang

    2017-01-01

    Full Text Available Increasing evidence suggests that intestinal dysbiosis, intestinal barrier dysfunction, and activated Toll-like receptor 4 (TLR4 signaling play key roles in the pathogenesis of NAFLD. Dahuang Zexie Decoction (DZD has been verified to be effective for treating NAFLD, but the mechanisms remain unclear. In this study, we investigated the effects of DZD on NAFLD rats and determined whether such effects were associated with change of the gut microbiota, downregulated activity of the TLR4 signaling pathway, and increased expressions of tight junction (TJ proteins in the gut. Male Sprague Dawley rats were fed high-fat diet (HFD for 16 weeks to induce NAFLD and then given DZD intervention for 4 weeks. We found that DZD reduced body and liver weights of NAFLD rats, improved serum lipid levels and liver function parameters, and relieved NAFLD. We further found that DZD changed intestinal bacterial communities, inhibited the intestinal TLR4 signaling pathway, and restored the expressions of TJ proteins in the gut. Meanwhile ten potential components of DZD had been identified. These findings suggest that DZD may protects against NAFLD by modulating gut microbiota-mediated TLR4 signaling activation and loss of intestinal barrier. However, further studies are needed to clarify the mechanism by which DZD treats NAFLD.

  1. Temporal pattern of loss/persistence of duplicate genes involved in signal transduction and metabolic pathways after teleost-specific genome duplication

    Directory of Open Access Journals (Sweden)

    Sato Yukuto

    2009-06-01

    Full Text Available Abstract Background Recent genomic studies have revealed a teleost-specific third-round whole genome duplication (3R-WGD event occurred in a common ancestor of teleost fishes. However, it is unclear how the genes duplicated in this event were lost or persisted during the diversification of teleosts, and therefore, how many of the duplicated genes contribute to the genetic differences among teleosts. This subject is also important for understanding the process of vertebrate evolution through WGD events. We applied a comparative evolutionary approach to this question by focusing on the genes involved in long-term potentiation, taste and olfactory transduction, and the tricarboxylic acid cycle, based on the whole genome sequences of four teleosts; zebrafish, medaka, stickleback, and green spotted puffer fish. Results We applied a state-of-the-art method of maximum-likelihood phylogenetic inference and conserved synteny analyses to each of 130 genes involved in the above biological systems of human. These analyses identified 116 orthologous gene groups between teleosts and tetrapods, and 45 pairs of 3R-WGD-derived duplicate genes among them. This suggests that more than half [(45×2/(116+45] = 56.5% of the loci, probably more than ten thousand genes, present in a common ancestor of the four teleosts were still duplicated after the 3R-WGD. The estimated temporal pattern of gene loss suggested that, after the 3R-WGD, many (71/116 of the duplicated genes were rapidly lost during the initial 75 million years (MY, whereas on average more than half (27.3/45 of the duplicated genes remaining in the ancestor of the four teleosts (45/116 have persisted for about 275 MY. The 3R-WGD-derived duplicates that have persisted for a long evolutionary periods of time had significantly larger number of interacting partners and longer length of protein coding sequence, implying that they tend to be more multifunctional than the singletons after the 3R-WGD. Conclusion

  2. Temporal pattern of loss/persistence of duplicate genes involved in signal transduction and metabolic pathways after teleost-specific genome duplication

    Science.gov (United States)

    Sato, Yukuto; Hashiguchi, Yasuyuki; Nishida, Mutsumi

    2009-01-01

    Background Recent genomic studies have revealed a teleost-specific third-round whole genome duplication (3R-WGD) event occurred in a common ancestor of teleost fishes. However, it is unclear how the genes duplicated in this event were lost or persisted during the diversification of teleosts, and therefore, how many of the duplicated genes contribute to the genetic differences among teleosts. This subject is also important for understanding the process of vertebrate evolution through WGD events. We applied a comparative evolutionary approach to this question by focusing on the genes involved in long-term potentiation, taste and olfactory transduction, and the tricarboxylic acid cycle, based on the whole genome sequences of four teleosts; zebrafish, medaka, stickleback, and green spotted puffer fish. Results We applied a state-of-the-art method of maximum-likelihood phylogenetic inference and conserved synteny analyses to each of 130 genes involved in the above biological systems of human. These analyses identified 116 orthologous gene groups between teleosts and tetrapods, and 45 pairs of 3R-WGD-derived duplicate genes among them. This suggests that more than half [(45×2)/(116+45)] = 56.5%) of the loci, probably more than ten thousand genes, present in a common ancestor of the four teleosts were still duplicated after the 3R-WGD. The estimated temporal pattern of gene loss suggested that, after the 3R-WGD, many (71/116) of the duplicated genes were rapidly lost during the initial 75 million years (MY), whereas on average more than half (27.3/45) of the duplicated genes remaining in the ancestor of the four teleosts (45/116) have persisted for about 275 MY. The 3R-WGD-derived duplicates that have persisted for a long evolutionary periods of time had significantly larger number of interacting partners and longer length of protein coding sequence, implying that they tend to be more multifunctional than the singletons after the 3R-WGD. Conclusion We have shown firstly

  3. Incorporation of Tin on copper clad laminate to increase the interface adhesion for signal loss reduction of high-frequency PCB lamination

    Science.gov (United States)

    Wang, Chong; Wen, Na; Zhou, Guoyun; Wang, Shouxu; He, Wei; Su, Xinhong; Hu, Yongsuan

    2017-11-01

    A novel method of improving the adhesion between copper and prepreg in high frequency PCB was proposed and studied in this work. This process which aimed to decrease the IEP (isoelectric point) of the copper to obtain higher adhesion, was achieved by depositing a thin tin layer with lower IEP on copper. It was characterized by scanning electron microscopy (SEM), 3D microscope, peel strength test, X-Ray thickness test, grazing incidence X-ray diffraction (GXRD), X-ray photoelectron spectroscopy (XPS), Agilent vector network analyzer (VNA), which confirmed its excellent adhesion performance and outstanding electrical properties in high-frequency signal transmission compared with traditional brown oxide method. Moreover, the mechanism of achieving high adhesion for this method was also investigated.

  4. Conservation of the abscission signaling peptide IDA during Angiosperm evolution: withstanding genome duplications and gain and loss of the receptors HAE/HSL2.

    Science.gov (United States)

    Stø, Ida M; Orr, Russell J S; Fooyontphanich, Kim; Jin, Xu; Knutsen, Jonfinn M B; Fischer, Urs; Tranbarger, Timothy J; Nordal, Inger; Aalen, Reidunn B

    2015-01-01

    The peptide INFLORESCENCE DEFICIENT IN ABSCISSION (IDA), which signals through the leucine-rich repeat receptor-like kinases HAESA (HAE) and HAESA-LIKE2 (HSL2), controls different cell separation events in Arabidopsis thaliana. We hypothesize the involvement of this signaling module in abscission processes in other plant species even though they may shed other organs than A. thaliana. As the first step toward testing this hypothesis from an evolutionarily perspective we have identified genes encoding putative orthologs of IDA and its receptors by BLAST searches of publically available protein, nucleotide and genome databases for angiosperms. Genes encoding IDA or IDA-LIKE (IDL) peptides and HSL proteins were found in all investigated species, which were selected as to represent each angiosperm order with available genomic sequences. The 12 amino acids representing the bioactive peptide in A. thaliana have virtually been unchanged throughout the evolution of the angiosperms; however, the number of IDL and HSL genes varies between different orders and species. The phylogenetic analyses suggest that IDA, HSL2, and the related HSL1 gene, were present in the species that gave rise to the angiosperms. HAE has arisen from HSL1 after a genome duplication that took place after the monocot-eudicots split. HSL1 has also independently been duplicated in the monocots, while HSL2 has been lost in gingers (Zingiberales) and grasses (Poales). IDA has been duplicated in eudicots to give rise to functionally divergent IDL peptides. We postulate that the high number of IDL homologs present in the core eudicots is a result of multiple whole genome duplications (WGD). We substantiate the involvement of IDA and HAE/HSL2 homologs in abscission by providing gene expression data of different organ separation events from various species.

  5. Indirubin-3'-oxime, an activator of Wnt/β-catenin signaling, enhances osteogenic commitment of ST2 cells and restores bone loss in high-fat diet-induced obese male mice.

    Science.gov (United States)

    Zahoor, Muhammad; Cha, Pu-Hyeon; Choi, Kang-Yell

    2014-08-01

    Obesity is a growing issue of the modern world, and its negative impact on bones in obese male patients has been recently reported. The Wnt/β-catenin pathway has an established role in the regulation of body fat content and bone density. We investigated the effects of indirubin-3'-oxime (I3O), the GSK3β inhibitor that activates Wnt/β-catenin signaling, on trabecular bone in high-fat diet (HFD)-induced obese male mice. I3O reverses the downregulating effect of fatty acid (FA) on Wnt/β-catenin signaling and enhances the osteogenic commitment of the bone marrow-derived stromal cell line ST2. FA induces the adipogenic differentiation of bone marrow stromal cells in vitro. In a male mouse model of HFD-induced obesity, trabecular bone loss was observed in the femora, with a gross increase in abdominal fat; however, the HFD effects were rescued with the activation of Wnt/β-catenin signaling by I3O treatment. I3O administration also reversed the increase in the number of HFD-induced adipocytes in the femur bone marrow in trabecular bone. Overall, our results indicate that I3O could be a potential therapeutic agent for obese male patients through downregulation of abdominal fat and net increment in trabecular bone density. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Chronic CNS oxytocin signaling preferentially induces fat loss in high-fat diet-fed rats by enhancing satiety responses and increasing lipid utilization

    Science.gov (United States)

    Thompson, Benjamin W.; Anekonda, Vishwanath T.; Ho, Jacqueline M.; Graham, James L.; Roberts, Zachary S.; Hwang, Bang H.; Ogimoto, Kayoko; Wolden-Hanson, Tami; Nelson, Jarrell; Kaiyala, Karl J.; Havel, Peter J.; Bales, Karen L.; Morton, Gregory J.; Schwartz, Michael W.; Baskin, Denis G.

    2016-01-01

    Based largely on a number of short-term administration studies, growing evidence suggests that central oxytocin is important in the regulation of energy balance. The goal of the current work is to determine whether long-term third ventricular (3V) infusion of oxytocin into the central nervous system (CNS) is effective for obesity prevention and/or treatment in rat models. We found that chronic 3V oxytocin infusion between 21 and 26 days by osmotic minipumps both reduced weight gain associated with the progression of high-fat diet (HFD)-induced obesity and elicited a sustained reduction of fat mass with no decrease of lean mass in rats with established diet-induced obesity. We further demonstrated that these chronic oxytocin effects result from 1) maintenance of energy expenditure at preintervention levels despite ongoing weight loss, 2) a reduction in respiratory quotient, consistent with increased fat oxidation, and 3) an enhanced satiety response to cholecystokinin-8 and associated decrease of meal size. These weight-reducing effects persisted for approximately 10 days after termination of 3V oxytocin administration and occurred independently of whether sucrose was added to the HFD. We conclude that long-term 3V administration of oxytocin to rats can both prevent and treat diet-induced obesity. PMID:26791828

  7. Loss of Phosphatase and tensin homologue deleted on chromosome 10 engages ErbB3 and IGF-IR signaling to promote antiestrogen resistance in breast cancer

    Science.gov (United States)

    Miller, Todd W.; Pérez-Torres, Marianela; Narasanna, Archana; Guix, Marta; Stål, Olle; Pérez-Tenorio, Gizeh; Gonzalez-Angulo, Ana M.; Hennessy, Bryan T.; Mills, Gordon B.; Kennedy, J. Phillip; Lindsley, Craig W.; Arteaga, Carlos L.

    2009-01-01

    Knockdown of the tumor suppressor phosphatase PTEN with shRNA in three estrogen receptor (ER)-positive breast cancer cell lines resulted in increased PI3K and AKT activities, resistance to tamoxifen and fulvestrant, and hormone-independent growth. PTEN knockdown induced the upregulation of ER transcriptional activity in MCF-7 cells, but decreased ER protein levels and transcriptional activity in T47D and MDA-361 cells. Tamoxifen and fulvestrant treatment inhibited estradiol-induced ER transcriptional activity in all shPTEN cell lines but did not abrogate the increased cell proliferation induced by PTEN knockdown. PTEN knockdown increased basal and ligand-induced activation of the IGF-I and ErbB3 receptor tyrosine kinases, and prolonged the association of the p85 PI3K subunit with the IGF-IR effector IRS-1 and with ErbB3, implicating PTEN in the modulation of signaling upstream of PI3K. Consistent with these data, PTEN levels inversely correlated with levels of tyrosine-phosphorylated IGF-IR in tissue lysate arrays of primary breast cancers. Inhibition of IGF-IR and/or ErbB2-mediated activation of ErbB3 with tyrosine kinase inhibitors restored hormone-dependence and the growth inhibitory effect of tamoxifen and fulvestrant on shPTEN cells, suggesting that co-targeting both ER and receptor tyrosine kinase pathways holds promise for the treatment of patients with ER+, PTEN-deficient breast cancers. PMID:19435893

  8. Loss of WNT-TCF addiction and enhancement of HH-GLI1 signalling define the metastatic transition of human colon carcinomas.

    Science.gov (United States)

    Varnat, Frédéric; Siegl-Cachedenier, Irene; Malerba, Monica; Gervaz, Pascal; Ruiz i Altaba, Ariel

    2010-11-01

    Previous studies demonstrate the initiation of colon cancers through deregulation of WNT-TCF signalling. An accepted but untested extension of this finding is that incurable metastatic colon carcinomas (CCs) universally remain WNT-TCF-dependent, prompting the search for WNT-TCF inhibitors. CCs and their stem cells also require Hedgehog (HH)-GLI1 activity, but how these pathways interact is unclear. Here we define coincident high-to-low WNT-TCF and low-to-high HH-GLI transitions in patient CCs, most strikingly in their CD133(+) stem cells, that mark the development of metastases. We find that enhanced HH-GLI mimics this transition, driving also an embryonic stem (ES)-like stemness signature and that GLI1 can be regulated by multiple CC oncogenes. The data support a model in which the metastatic transition involves the acquisition or enhancement of a more primitive ES-like phenotype, and the downregulation of the early WNT-TCF programme, driven by oncogene-regulated high GLI1 activity. Consistently, TCF blockade does not generally inhibit tumour growth; instead, it, like enhanced HH-GLI, promotes metastatic growth in vivo. Treatments for metastatic disease should therefore block HH-GLI1 but not WNT-TCF activities.

  9. Specific epiblast loss and hypoblast impairment in cattle embryos sensitized to survival signalling by ubiquitous overexpression of the proapoptotic gene BAD.

    Directory of Open Access Journals (Sweden)

    Jessica van Leeuwen

    Full Text Available Early embryonic lethality is common, particularly in dairy cattle. We made cattle embryos more sensitive to environmental stressors by raising the threshold of embryo survival signaling required to overcome the deleterious effects of overexpressing the proapoptotic protein BAD. Two primary fibroblast cell lines expressing BAD and exhibiting increased sensitivity to stress-induced apoptosis were used to generate transgenic Day 13/14 BAD embryos. Transgenic embryos were normal in terms of retrieval rates, average embryo length or expression levels of the trophectoderm marker ASCL2. However both lines of BAD-tg embryos lost the embryonic disc and thus the entire epiblast lineage at significantly greater frequencies than either co-transferrred IVP controls or LacZ-tg embryos. Embryos without epiblast still contained the second ICM-derived lineage, the hypopblast, albeit frequently in an impaired state, as shown by reduced expression of the hypoblast markers GATA4 and FIBRONECTIN. This indicates a gradient of sensitivity (epiblast > hypoblast > TE to BAD overexpression. We postulate that the greater sensitivity of specifically the epiblast lineage that we have seen in our transgenic model, reflects an inherent greater susceptibility of this lineage to environmental stress and may underlie the epiblast-specific death seen in phantom pregnancies.

  10. Loss of miR-101 expression promotes Wnt/β-catenin signalling pathway activation and malignancy in colon cancer cells.

    Science.gov (United States)

    Strillacci, Antonio; Valerii, Maria Chiara; Sansone, Pasquale; Caggiano, Cinzia; Sgromo, Annamaria; Vittori, Laura; Fiorentino, Michelangelo; Poggioli, Gilberto; Rizzello, Fernando; Campieri, Massimo; Spisni, Enzo

    2013-02-01

    Colorectal cancer (CRC) is the second leading cause of cancer-related mortality in Western countries. Although the aberrant expression of several microRNAs (oncomiRs) is associated with CRC progression, the molecular mechanisms of this phenomenon are still under investigation. Here we show that miR-101 expression is differentially impaired in CRC specimens, depending on tumour grade. miR-101 re-expression suppresses cell growth in 3D, hypoxic survival and invasive potential in CRC cells showing low levels of miR-101. Additionally, we provide molecular evidence of a bidirectional regulatory mechanism between miR-101 expression and important CRC pro-malignant features, such as inflammation, activation of the Wnt/β-catenin signalling pathway and epithelial-mesenchymal transition (EMT). We then propose that up-regulated miR-101 may function as a tumour suppressor in CRC and that its pharmacological restoration might hamper the aggressive behaviour of CRC in vivo. MiR-101 expression may also represent a cancer biomarker for CRC diagnosis and prognosis. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  11. Loss of miR-10a activates lpo and collaborates with activated Wnt signaling in inducing intestinal neoplasia in female mice.

    Directory of Open Access Journals (Sweden)

    Gustavo Stadthagen

    2013-10-01

    Full Text Available miRNAs are small regulatory RNAs that, due to their considerable potential to target a wide range of mRNAs, are implicated in essentially all biological process, including cancer. miR-10a is particularly interesting considering its conserved location in the Hox cluster of developmental regulators. A role for this microRNA has been described in developmental regulation as well as for various cancers. However, previous miR-10a studies are exclusively based on transient knockdowns of this miRNA and to extensively study miR-10a loss we have generated a miR-10a knock out mouse. Here we show that, in the Apc(min mouse model of intestinal neoplasia, female miR-10a deficient mice develop significantly more adenomas than miR-10(+/+ and male controls. We further found that Lpo is extensively upregulated in the intestinal epithelium of mice deprived of miR-10a. Using in vitro assays, we demonstrate that the primary miR-10a target KLF4 can upregulate transcription of Lpo, whereas siRNA knockdown of KLF4 reduces LPO levels in HCT-116 cells. Furthermore, Klf4 is upregulated in the intestines of miR-10a knockout mice. Lpo has previously been shown to have the capacity to oxidize estrogens into potent depurinating mutagens, creating an instable genomic environment that can cause initiation of cancer. Therefore, we postulate that Lpo upregulation in the intestinal epithelium of miR-10a deficient mice together with the predominant abundance of estrogens in female animals mainly accounts for the sex-related cancer phenotype we observed. This suggests that miR-10a could be used as a potent diagnostic marker for discovering groups of women that are at high risk of developing colorectal carcinoma, which today is one of the leading causes of cancer-related deaths.

  12. Spatio-temporal dynamics of multimodal EEG-fNIRS signals in the loss and recovery of consciousness under sedation using midazolam and propofol.

    Science.gov (United States)

    Yeom, Seul-Ki; Won, Dong-Ok; Chi, Seong In; Seo, Kwang-Suk; Kim, Hyun Jeong; Müller, Klaus-Robert; Lee, Seong-Whan

    2017-01-01

    On sedation motivated by the clinical needs for safety and reliability, recent studies have attempted to identify brain-specific signatures for tracking patient transition into and out of consciousness, but the differences in neurophysiological effects between 1) the sedative types and 2) the presence/absence of surgical stimulations still remain unclear. Here we used multimodal electroencephalography-functional near-infrared spectroscopy (EEG-fNIRS) measurements to observe electrical and hemodynamic responses during sedation simultaneously. Forty healthy volunteers were instructed to push the button to administer sedatives in response to auditory stimuli every 9-11 s. To generally illustrate brain activity at repetitive transition points at the loss of consciousness (LOC) and the recovery of consciousness (ROC), patient-controlled sedation was performed using two different sedatives (midazolam (MDZ) and propofol (PPF)) under two surgical conditions. Once consciousness was lost via sedatives, we observed gradually increasing EEG power at lower frequencies (15 Hz), as well as spatially increased EEG powers in the delta and lower alpha bands, and particularly also in the upper alpha rhythm, at the frontal and parieto-occipital areas over time. During ROC from unconsciousness, these spatio-temporal changes were reversed. Interestingly, the level of consciousness was switched on/off at significantly higher effect-site concentrations of sedatives in the brain according to the use of surgical stimuli, but the spatio-temporal EEG patterns were similar, regardless of the sedative used. We also observed sudden phase shifts in fronto-parietal connectivity at the LOC and the ROC as critical points. fNIRS measurement also revealed mild hemodynamic fluctuations. Compared with general anesthesia, our results provide insights into critical hallmarks of sedative-induced (un)consciousness, which have similar spatio-temporal EEG-fNIRS patterns regardless of the stage and the

  13. Memory loss

    Science.gov (United States)

    ... amnesia (sudden, temporary loss of memory) of unclear cause Transient ischemic attack (TIA) or stroke Hydrocephalus (fluid collection in the brain) Sometimes, memory loss occurs with mental health problems, such as: After a major, traumatic or stressful ...

  14. Hair Loss

    Science.gov (United States)

    ... overall hair thinning and not bald patches. Full-body hair loss. Some conditions and medical treatments, such as ... in the loss of hair all over your body. The hair usually grows back. Patches of scaling that spread ...

  15. Experiencing Loss

    DEFF Research Database (Denmark)

    Kristiansen, Maria; Younis, Tarek; Hassani, Amani

    2015-01-01

    , who narrates her experience of losing herhusband to lung cancer. By drawing on a religious framework, Aisha creates meaning fromher loss, which enables her to incorporate this loss into her life history and sustain agency.Her narrative invites wider audiences to witness her tale of overcoming loss...

  16. Loss of the SxxSS motif in a human T-cell factor-4 isoform confers hypoxia resistance to liver cancer: an oncogenic switch in Wnt signaling.

    Directory of Open Access Journals (Sweden)

    Hironori Koga

    Full Text Available PURPOSE: Aberrantly activated Wnt/β-catenin signaling is important in hepatocellular carcinoma (HCC development. Downstream gene expressions involving the Wnt/β-catenin cascade occur through T-cell factor (TCF proteins. Here, we show the oncogenic potential of human TCF-4 isoforms based on the expression of a single conserved SxxSS motif. METHODS: We investigated the TCF-4J and K isoform pair characterized by the presence (K or absence (J of the SxxSS motif. The mRNA expression profiles were examined in 47 pairs of human HCCs and adjacent non-cancerous liver tissues by RT-PCR. Proliferation, sphere assays and immunoblot analysis were performed under normoxia and hypoxia conditions. The ability of HCC cells overexpressing TCF-4J (J cells and K (K cells to grow as solid tumors in nude mice was explored. RESULTS: TCF-4J expression was significantly upregulated in HCC tumors compared to corresponding peritumor and normal liver and was preferentially expressed in poorly differentiated HCCs. In contrast, TCF-4K was downregulated in those same HCC tumors. TCF-4J-overexpressing HCC cells (J cells revealed a survival advantage under hypoxic conditions, high proliferation rate and formation of aggregates/spheres compared to overexpression of TCF-4K (K cells. The hypoxic J cells had high expression levels of HIF-2α and EGFR as possible mechanisms to promote tumorigenesis. Increased stability of HIF-2α under hypoxia in J cells was associated with a decreased level of von Hippel-Lindau (VHL protein, a known E3 ligase for HIF-αs. In a xenograft model, the J cells rapidly developed tumors compared to K cells. Tumor tissues derived from J cells exhibited high expression levels of HIF-2α and EGFR compared to the slow developing and small K cell derived tumors. CONCLUSIONS: Our results suggest that the specific TCF-4J isoform, which lacks a regulatory SxxSS motif, has robust tumor-initiating potential under hypoxic conditions.

  17. Formononetin, an isoflavone, activates AMP-activated protein kinase/β-catenin signalling to inhibit adipogenesis and rescues C57BL/6 mice from high-fat diet-induced obesity and bone loss.

    Science.gov (United States)

    Gautam, Jyoti; Khedgikar, Vikram; Kushwaha, Priyanka; Choudhary, Dharmendra; Nagar, Geet Kumar; Dev, Kapil; Dixit, Preety; Singh, Divya; Maurya, Rakesh; Trivedi, Ritu

    2017-03-01

    Balance between adipocyte and osteoblast differentiation is the key link of disease progression in obesity and osteoporosis. We have previously reported that formononetin (FNT), an isoflavone extracted from Butea monosperma, stimulates osteoblast formation and protects against postmenopausal bone loss. The inverse relationship between osteoblasts and adipocytes prompted us to analyse the effect of FNT on adipogenesis and in vivo bone loss, triggered by high-fat diet (HFD)-induced obesity. The anti-obesity effect and mechanism of action of FNT was determined in 3T3-L1 cells and HFD-induced obese male mice. Our findings show that FNT suppresses the adipogenic differentiation of 3T3-L1 fibroblasts, through down-regulation of key adipogenic markers such as PPARγ, CCAAT/enhancer-binding protein alpha (C/EBPα) and sterol regulatory element-binding protein (SREBP) and inhibits intracellular TAG accumulation. Increased intracellular reactive oxygen species levels and AMP-activated protein kinase (AMPK) activation accompanied by stabilisation of β-catenin were attributed to the anti-adipogenic action of FNT. In vivo, 12 weeks of FNT treatment inhibited the development of obesity in mice by attenuating HFD-induced body weight gain and visceral fat accumulation. The anti-obesity effect of FNT results from increased energy expenditure. FNT also protects against HFD-induced dyslipidaemia and rescues deterioration of trabecular bone volume by increasing bone formation and decreasing bone resorbtion caused by HFD. FNT's rescuing action against obesity-induced osteoporosis commenced at the level of progenitors, as bone marrow progenitor cells, obtained from the HFD mice group supplemented with FNT, showed increased osteogenic and decreased adipogenic potentials. Our findings suggest that FNT inhibits adipogenesis through AMPK/β-catenin signal transduction pathways and protects against HFD-induced obesity and bone loss.

  18. Loss of P53 Function Activates JAK2-STAT3 Signaling to Promote Pancreatic Tumor Growth, Stroma Modification, and Gemcitabine Resistance in Mice and Is Associated With Patient Survival.

    Science.gov (United States)

    Wörmann, Sonja M; Song, Liang; Ai, Jiaoyu; Diakopoulos, Kalliope N; Kurkowski, Magdalena U; Görgülü, Kivanc; Ruess, Dietrich; Campbell, Andrew; Doglioni, Claudio; Jodrell, Duncan; Neesse, Albrecht; Demir, Ihsan E; Karpathaki, Angelica-Phaedra; Barenboim, Maxim; Hagemann, Thorsten; Rose-John, Stefan; Sansom, Owen; Schmid, Roland M; Protti, Maria P; Lesina, Marina; Algül, Hana

    2016-07-01

    One treatment strategy for pancreatic ductal adenocarcinoma is to modify, rather than deplete, the tumor stroma. Constitutive activation of the signal transducer and activator of transcription 3 (STAT3) is associated with progression of pancreatic and other solid tumors. We investigated whether loss of P53 function contributes to persistent activation of STAT3 and modification of the pancreatic tumor stroma in patients and mice. Stat3, Il6st (encodes gp130), or Trp53 were disrupted, or a mutant form of P53 (P53R172H) or transgenic sgp130 were expressed, in mice that developed pancreatic tumors resulting from expression of activated KRAS (KrasG12D, KC mice). Pancreata were collected and analyzed by immunohistochemistry, in situ hybridization, quantitative reverse-transcription polymerase chain reaction (qPCR), or immunoblot assays; fluorescence-activated cell sorting was performed to identify immune cells. We obtained frozen pancreatic tumor specimens from patients and measured levels of phosphorylated STAT3 and P53 by immunohistochemistry; protein levels were associated with survival using Kaplan-Meier analyses. We measured levels of STAT3, P53, ligands for gp130, interleukin 6, cytokines, sonic hedgehog signaling, STAT3 phosphorylation (activation), and accumulation of reactive oxygen species in primary pancreatic cells from mice. Mice with pancreatic tumors were given gemcitabine and a Janus kinase 2 (JAK2) inhibitor; tumor growth was monitored by 3-dimensional ultrasound. STAT3 was phosphorylated constitutively in pancreatic tumor cells from KC mice with loss or mutation of P53. Tumor cells of these mice accumulated reactive oxygen species and had lower activity of the phosphatase SHP2 and prolonged phosphorylation of JAK2 compared with tumors from KC mice with functional P53. These processes did not require the gp130 receptor. Genetic disruption of Stat3 in mice, or pharmacologic inhibitors of JAK2 or STAT3 activation, reduced fibrosis and the numbers of

  19. Hair Loss

    Science.gov (United States)

    ... to treat acne, bipolar disorder, and ADHD. Diet pills that contain amphetamines also can cause hair loss. Alopecia areata (pronounced: al-uh-PEE-shuh air-ee-AH-tuh) . This skin disease causes hair ...

  20. Loss of BMI-1 dampens migration and EMT of colorectal cancer in inflammatory microenvironment through TLR4/MD-2/MyD88-mediated NF-κB signaling.

    Science.gov (United States)

    Ye, Kai; Chen, Qi-Wei; Sun, Ya-Feng; Lin, Jian-An; Xu, Jian-Hua

    2017-08-16

    Increasing evidence from various clinical and experimental studies has demonstrated that the inflammatory microenvironment created by immune cells facilitates tumor migration. Epithelial-mesenchymal transition (EMT) is involved in the progression of cancer invasion and metastasis in an inflammatory microenvironment. B-lymphoma Moloney murine leukemia virus insertion region 1 (BMI-1) acts as an oncogene in various tumors. Ectopic expression of Bmi-1 have an effect on EMT and invasiveness. The purpose of this study was to investigate the efficacy of BMI-1 on inflammation-induced tumor migration and EMT and the underlying mechanism. We observed that the expression of BMI-1, TNF-α, and IL-1β was significantly increased in HT29 and HCT116 cells after THP-1 Conditioned-Medium (THP-1-CM) stimulation. Additionally, inhibition of BMI-1 impeded cell invasion induced by THP-1-CM-stimulation in both HT29 and HCT116 cells. BMI-1 knockdown remarkably repressed THP-1-CM-induced EMT by regulating the expression of EMT biomarkers with an increase in E-cadherin accompanied by decrease in N-cadherin and vimentin. Furthermore, downregulation of BMI-1 dramatically impeded THP-1-CM-triggered Toll-like receptor 4(TLR4)/myeloid differentiation protein 2(MD-2)/myeloid differentiation factor 88(MyD88) activity by repressing the expression of the TLR4/MD-2 complex and MyD88. Further data demonstrated that knockout of BMI-1 also dampened NF-κB THP-1-CM-triggered activity. Taken all data together, our findings established that BMI-1 modulated TLR4/MD-2/MyD88 complex-mediated NF-κB signaling involved in inflammation-induced cancer cells invasion and EMT, and therefore, could be a potential chemopreventive agent against inflammation-associated colorectal cancer. Establishment of an inflammatory microenvironment. Suppression of BMI-1 reverses THP-1-CM-induced inflammatory cytokine production in CRC. Loss of BMI-1 suppressed TLR4/MD-2/MyD88 complex-mediated NF-κB signaling. © 2017 Wiley

  1. Hair Loss

    Science.gov (United States)

    ... hair if you have certain diseases, such as thyroid problems, diabetes, or lupus. If you take certain medicines or have chemotherapy for cancer, you may also lose your hair. Other causes are stress, a low protein diet, a family history, or poor nutrition. Treatment for hair loss depends ...

  2. Hearing Loss

    Science.gov (United States)

    ... birth defects and other medical conditions run in families, and how they can affect your health and your baby's health. There are ... Too Soon Global Map Premature birth report card Careers Archives ... Family health & safety Complications & Loss Pregnancy complications Preterm labor & ...

  3. Loss engineered slow light waveguides.

    Science.gov (United States)

    O'Faolain, L; Schulz, S A; Beggs, D M; White, T P; Spasenović, M; Kuipers, L; Morichetti, F; Melloni, A; Mazoyer, S; Hugonin, J P; Lalanne, P; Krauss, T F

    2010-12-20

    Slow light devices such as photonic crystal waveguides (PhCW) and coupled resonator optical waveguides (CROW) have much promise for optical signal processing applications and a number of successful demonstrations underpinning this promise have already been made. Most of these applications are limited by propagation losses, especially for higher group indices. These losses are caused by technological imperfections ("extrinsic loss") that cause scattering of light from the waveguide mode. The relationship between this loss and the group velocity is complex and until now has not been fully understood. Here, we present a comprehensive explanation of the extrinsic loss mechanisms in PhC waveguides and address some misconceptions surrounding loss and slow light that have arisen in recent years. We develop a theoretical model that accurately describes the loss spectra of PhC waveguides. One of the key insights of the model is that the entire hole contributes coherently to the scattering process, in contrast to previous models that added up the scattering from short sections incoherently. As a result, we have already realised waveguides with significantly lower losses than comparable photonic crystal waveguides as well as achieving propagation losses, in units of loss per unit time (dB/ns) that are even lower than those of state-of-the-art coupled resonator optical waveguides based on silicon photonic wires. The model will enable more advanced designs with further loss reduction within existing technological constraints.

  4. Detection of Equipment Faults Before Beam Loss

    CERN Document Server

    Galambos, J.

    2016-01-01

    High-power hadron accelerators have strict limits on fractional beam loss. In principle, once a high-quality beam is set up in an acceptable state, beam loss should remain steady. However, in practice, there are many trips in operational machines, owing to excessive beam loss. This paper deals with monitoring equipment health to identify precursor signals that indicate an issue with equipment that will lead to unacceptable beam loss. To this end, a variety of equipment and beam signal measurements are described. In particular, several operational examples from the Spallation Neutron Source (SNS) of deteriorating equipment functionality leading to beam loss are reported.

  5. 47 CFR 80.769 - Shadow loss.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 5 2010-10-01 2010-10-01 false Shadow loss. 80.769 Section 80.769... MARITIME SERVICES Standards for Computing Public Coast Station VHF Coverage § 80.769 Shadow loss. Where the transmission path is obstructed the received signal must be adjusted to include shadow loss. Attenuation due to...

  6. Loss Networks

    OpenAIRE

    Kelly, F. P.

    1991-01-01

    This paper describes work on the stochastic modelling of loss networks. Such systems have long been of interest to telephone engineers and are becoming increasingly important as models of computer and information systems. Throughout the century problems from this field have provided an impetus to the development of probability theory, pure and applied. This paper provides an introduction to the area and a review of recent work.

  7. Signal Words

    Science.gov (United States)

    SIGNAL WORDS TOPIC FACT SHEET NPIC fact sheets are designed to answer questions that are commonly asked by the ... making decisions about pesticide use. What are Signal Words? Signal words are found on pesticide product labels, ...

  8. Weight-loss medicines

    Science.gov (United States)

    Prescription weight loss drugs; Diabetes - weight loss drugs; Obesity - weight loss drugs; Overweight - weight loss drugs ... are not approved by the FDA to treat weight-loss. So you should not take them if you do not have diabetes.

  9. Hearing Loss in Children

    Science.gov (United States)

    ... Hearing Loss Homepage Facts Noise-Induced Hearing Loss Genetics of Hearing Loss Screening & Diagnosis Types of Hearing Loss About Sound Treatment & Intervention Services Learning Language Bacterial Meningitis Studies Data & Statistics EHDI Annual Data 2015 ...

  10. Genetics of Hearing Loss

    Science.gov (United States)

    ... Hearing Loss Homepage Facts Noise-Induced Hearing Loss Genetics of Hearing Loss Screening & Diagnosis Types of Hearing Loss About Sound Treatment & Intervention Services Learning Language Bacterial Meningitis Studies Data & Statistics EHDI Annual Data 2015 ...

  11. Managing Hearing Loss

    Science.gov (United States)

    ... page please turn JavaScript on. Feature: Hearing Loss Managing Hearing Loss Past Issues / Spring 2015 Table of ... not a cure. Read More "Hearing Loss" Articles Managing Hearing Loss / Symptoms, Devices, Prevention & Research / Screening Newborns / ...

  12. Bone Loss in IBD

    Science.gov (United States)

    ... Home > Resources > Bone Loss in IBD Go Back Bone Loss in IBD Email Print + Share As many as ... halt bone loss are so important. CAUSES OF BONE LOSS IN IBD Experts point to several suspected causes ...

  13. Loss of 50% of excess weight using a very low energy diet improves insulin-stimulated glucose disposal and skeletal muscle insulin signalling in obese insulin-treated type 2 diabetic patients

    NARCIS (Netherlands)

    Jazet, I. M.; Schaart, G.; Gastaldelli, A.; Ferrannini, E.; Hesselink, M. K.; Schrauwen, P.; Romijn, J. A.; Maassen, J. A.; Pijl, H.; Ouwens, D. M.; Meinders, A. E.

    2008-01-01

    Both energy restriction (ER) per se and weight loss improve glucose metabolism in obese insulin-treated type 2 diabetic patients. Short-term ER decreases basal endogenous glucose production (EGP) but not glucose disposal. In contrast the blood glucose-lowering mechanism of long-term ER with

  14. Quantum Key Distribution with High Loss: Toward Global Secure Communication

    Science.gov (United States)

    Hwang, Won-Young

    2003-08-01

    We propose a decoy-pulse method to overcome the photon-number-splitting attack for Bennett-Brassard 1984 quantum key distribution protocol in the presence of high loss: A legitimate user intentionally and randomly replaces signal pulses by multiphoton pulses (decoy pulses). Then they check the loss of the decoy pulses. If the loss of the decoy pulses is abnormally less than that of signal pulses, the whole protocol is aborted. Otherwise, to continue the protocol, they estimate the loss of signal multiphoton pulses based on that of decoy pulses. This estimation can be done with an assumption that the two losses have similar values. We justify that assumption.

  15. Digital Signal Treatment in Beam Instrumentation

    CERN Document Server

    Schilcher, T

    2001-01-01

    Digital Signal Processing has grown dramatically over the last five years. The evolution of digital logic and processors has opened up the use of digital signal processing in domains, which were reserved to analog signal processing. In this discussion session we would like to review digital signal treatment for beam diagnostics application. Emphasis shall be put on the following subjects: Digital Signal Processing for: image processing BPMs current monitors beam loss monitors feedback systems others

  16. Signaling aggression.

    Science.gov (United States)

    van Staaden, Moira J; Searcy, William A; Hanlon, Roger T

    2011-01-01

    From psychological and sociological standpoints, aggression is regarded as intentional behavior aimed at inflicting pain and manifested by hostility and attacking behaviors. In contrast, biologists define aggression as behavior associated with attack or escalation toward attack, omitting any stipulation about intentions and goals. Certain animal signals are strongly associated with escalation toward attack and have the same function as physical attack in intimidating opponents and winning contests, and ethologists therefore consider them an integral part of aggressive behavior. Aggressive signals have been molded by evolution to make them ever more effective in mediating interactions between the contestants. Early theoretical analyses of aggressive signaling suggested that signals could never be honest about fighting ability or aggressive intentions because weak individuals would exaggerate such signals whenever they were effective in influencing the behavior of opponents. More recent game theory models, however, demonstrate that given the right costs and constraints, aggressive signals are both reliable about strength and intentions and effective in influencing contest outcomes. Here, we review the role of signaling in lieu of physical violence, considering threat displays from an ethological perspective as an adaptive outcome of evolutionary selection pressures. Fighting prowess is conveyed by performance signals whose production is constrained by physical ability and thus limited to just some individuals, whereas aggressive intent is encoded in strategic signals that all signalers are able to produce. We illustrate recent advances in the study of aggressive signaling with case studies of charismatic taxa that employ a range of sensory modalities, viz. visual and chemical signaling in cephalopod behavior, and indicators of aggressive intent in the territorial calls of songbirds. Copyright © 2011 Elsevier Inc. All rights reserved.

  17. What's Hearing Loss?

    Science.gov (United States)

    ... Weight for Me? Your Teeth Heart Murmurs What's Hearing Loss? KidsHealth > For Kids > What's Hearing Loss? Print ... problem can also develop later in life. How Hearing Works To understand how and why hearing loss ...

  18. Genes and Hearing Loss

    Science.gov (United States)

    ... Find an ENT Doctor Near You Genes and Hearing Loss Genes and Hearing Loss Patient Health Information News media interested in ... One of the most common birth defects is hearing loss or deafness (congenital), which can affect as ...

  19. Pregnancy Loss and Miscarriage

    Science.gov (United States)

    ... Information Find a Study Resources and Publications Pregnancy Loss: Condition Information Skip sharing on social media links Share this: Page Content What is pregnancy loss/miscarriage? A miscarriage, also called pregnancy loss or ...

  20. Menopause and Bone Loss

    Science.gov (United States)

    ... up bone loss. After menopause your ovaries stop producing the hormone estrogen, which helps to keep your ... you minimize and treat bone loss? Diet and lifestyle can help prevent and treat bone loss. Successful ...

  1. Economic Loan Loss Provision and Expected Loss

    Directory of Open Access Journals (Sweden)

    Stefan Hlawatsch

    2010-10-01

    Full Text Available The intention of a loan loss provision is the anticipation of the loan's expected losses by adjusting the book value of the loan. Furthermore, this loan loss provision has to be compared to the expected loss according to Basel II and, in the case of a difference, liable equity has to be adjusted. This however assumes that the loan loss provision and the expected loss are based on a similar economic rationale, which is only valid conditionally in current loan loss provisioning methods according to IFRS. Therefore, differences between loan loss provisions and expected losses should only result from different approaches regarding the parameter estimation within each model and not due to different assumptions regarding the outcome of the model. The provisioning and accounting model developed in this paper overcomes the before-mentioned shortcomings and is consistent with an economic rationale of expected losses. Additionally, this model is based on a close-to-market valuation of the loan that is in favor of the basic idea of IFRS. Suggestions for changes in current accounting and capital requirement rules are provided.

  2. Theoretical analysis of the sensitivity of dipolar field signal to local field variations by perturbative expansion of the magnetization

    Science.gov (United States)

    Wong, Chung Ki

    2010-03-01

    A perturbation method based on the integral form of the Bloch equation is used to calculate the distant dipolar field (DDF) signal formed by the correlation spectroscopy revamped by asymmetric z-gradient echo detection (CRAZED) sequence in the presence of a susceptibility-induced field. The properties of the DDF signal are analyzed through the series expansion of the magnetization, and the first order DDF result is applied to study the use of the DDF effect to probe sub-voxel field distributions. Numerical calculations are carried out with the sub-voxel field distributions modeled by rectangular tubes of uniform frequency shifts (the block model) and cylinders of a finite susceptibility difference (the blood vessel model) using the parameters for brain at 9.4 T. The DDF signal is found to exhibit features arising from the sub-voxel structures.

  3. The Mammalian Orthologs of Drosophila Lgd, CC2D1A and CC2D1B, Function in the Endocytic Pathway, but Their Individual Loss of Function Does Not Affect Notch Signalling.

    Directory of Open Access Journals (Sweden)

    Nadja Drusenheimer

    2015-12-01

    Full Text Available CC2D1A and CC2D1B belong to the evolutionary conserved Lgd protein family with members in all multi-cellular animals. Several functions such as centrosomal cleavage, involvement in signalling pathways, immune response and synapse maturation have been described for CC2D1A. Moreover, the Drosophila melanogaster ortholog Lgd was shown to be involved in the endosomal trafficking of the Notch receptor and other transmembrane receptors and physically interacts with the ESCRT-III component Shrub/CHMP4. To determine if this function is conserved in mammals we generated and characterized Cc2d1a and Cc2d1b conditional knockout mice. While Cc2d1b deficient mice displayed no obvious phenotype, we found that Cc2d1a deficient mice as well as conditional mutants that lack CC2D1A only in the nervous system die shortly after birth due to respiratory distress. This finding confirms the suspicion that the breathing defect is caused by the central nervous system. However, an involvement in centrosomal function could not be confirmed in Cc2d1a deficient MEF cells. To analyse an influence on Notch signalling, we generated intestine specific Cc2d1a mutant mice. These mice did not display any alterations in goblet cell number, proliferating cell number or expression of the Notch reporter Hes1-emGFP, suggesting that CC2D1A is not required for Notch signalling. However, our EM analysis revealed that the average size of endosomes of Cc2d1a mutant cells, but not Cc2d1b mutant cells, is increased, indicating a defect in endosomal morphogenesis. We could show that CC2D1A and its interaction partner CHMP4B are localised on endosomes in MEF cells, when the activity of the endosomal protein VPS4 is reduced. This indicates that CC2D1A cycles between the cytosol and the endosomal membrane. Additionally, in rescue experiments in D. melanogaster, CC2D1A and CC2D1B were able to functionally replace Lgd. Altogether our data suggest a functional conservation of the Lgd protein family

  4. Blocking Losses With a Photon Counter

    Science.gov (United States)

    Moision, Burce E.; Piazzolla, Sabino

    2012-01-01

    It was not known how to assess accurately losses in a communications link due to photodetector blocking, a phenomenon wherein a detector is rendered inactive for a short time after the detection of a photon. When used to detect a communications signal, blocking leads to losses relative to an ideal detector, which may be measured as a reduction in the communications rate for a given received signal power, or an increase in the signal power required to support the same communications rate. This work involved characterizing blocking losses for single detectors and arrays of detectors. Blocking may be mitigated by spreading the signal intensity over an array of detectors, reducing the count rate on any one detector. A simple approximation was made to the blocking loss as a function of the probability that a detector is unblocked at a given time, essentially treating the blocking probability as a scaling of the detection efficiency. An exact statistical characterization was derived for a single detector, and an approximation for multiple detectors. This allowed derivation of several accurate approximations to the loss. Methods were also derived to account for a rise time in recovery, and non-uniform illumination due to diffraction and atmospheric distortion of the phase front. It was assumed that the communications signal is intensity modulated and received by an array of photon-counting photodetectors. For the purpose of this analysis, it was assumed that the detectors are ideal, in that they produce a signal that allows one to reproduce the arrival times of electrons, produced either as photoelectrons or from dark noise, exactly. For single detectors, the performance of the maximum-likelihood (ML) receiver in blocking is illustrated, as well as a maximum-count (MC) receiver, that, when receiving a pulse-position-modulated (PPM) signal, selects the symbol corresponding to the slot with the largest electron count. Whereas the MC receiver saturates at high count rates

  5. Hair loss in women.

    Science.gov (United States)

    Harfmann, Katya L; Bechtel, Mark A

    2015-03-01

    Hair loss is a common cause of morbidity for many women. As a key member of the woman's health care team, the obstetrician/gynecologist may be the first person to evaluate the complaint of hair loss. Common types of nonscarring hair loss, including female pattern hair loss and telogen effluvium, may be diagnosed and managed by the obstetrician/gynecologist. A systematic approach to diagnosis and management of these common forms of hair loss is presented.

  6. Hearing loss in pregnancy

    OpenAIRE

    Ashok Murthy, V.; Krishna, Kirtan

    2011-01-01

    To study hearing loss in healthy pregnant women. Tertiary care hospital. Prospective study. We screened fifty healthy, non-complicated pregnant women (study group) in the third trimester for hearing loss who had no previous history for the same. Fifty healthy, non-pregnant women (control group) were also screened for hearing loss with a normal pure tone audiogram (PTA) for evidence of hearing loss. Thirteen women in the study group had evidence of hearing loss, in the form of absence of disto...

  7. The osteoimmunology of alveolar bone loss.

    Science.gov (United States)

    Tompkins, Kevin A

    2016-01-01

    The mineralized structure of bone undergoes constant remodeling by the balanced actions of bone-producing osteoblasts and bone-resorbing osteoclasts (OCLs). Physiologic bone remodeling occurs in response to the body's need to respond to changes in electrolyte levels, or mechanical forces on bone. There are many pathological conditions, however, that cause an imbalance between bone production and resorption due to excessive OCL action that results in net bone loss. Situations involving chronic or acute inflammation are often associated with net bone loss, and research into understanding the mechanisms regulating this bone loss has led to the development of the field of osteoimmunology. It is now evident that the skeletal and immune systems are functionally linked and share common cells and signaling molecules. This review discusses the signaling system of immune cells and cytokines regulating aberrant OCL differentiation and activity. The role of these cells and cytokines in the bone loss occurring in periodontal disease (PD) (chronic inflammation) and orthodontic tooth movement (OTM) (acute inflammation) is then described. The review finishes with an exploration of the emerging role of Notch signaling in the development of the immune cells and OCLs that are involved in osteoimmunological bone loss and the research into Notch signaling in OTM and PD.

  8. Corona helps curb losses

    Energy Technology Data Exchange (ETDEWEB)

    Laasonen, M.; Lahtinen, M.; Lustre, L.

    1996-11-01

    The greatest power losses in electricity transmission arise through a phenomenon called load losses. Corona losses caused by the surface discharge of electricity also constitute a considerable cost item. IVS, the nationwide network company, is investigating corona- induced losses, and has also commissioned similar research from IVO International, the Technical Research Centre of Finland (VTT) and from Tampere University of Technology. The research work strives to gain more in-depth knowledge on the phenomenon of frosting and its impact on corona losses. The correct prediction of frost helps reduce corona losses, while also cutting costs considerably. (orig.)

  9. Telogen Effluvium Hair Loss

    Science.gov (United States)

    ... Category: Share: Yes No, Keep Private Telogen Effluvium Hair Loss Share | It is normal to lose up to ... months after the "shock". This sudden increase in hair loss, usually described as the hair coming out in ...

  10. What causes bone loss?

    Science.gov (United States)

    ... of bone loss. For men, a drop in testosterone as they age can cause bone loss. Your ... Wisse, MD, Associate Professor of Medicine, Division of Metabolism, Endocrinology & Nutrition, University of Washington School of Medicine, ...

  11. Injection losses and protection

    CERN Document Server

    Bartmann, W; Baudrenghien, P; Bracco, C; Dehning, B; Di Mauro, A; Drosdal, L; Emery, J; Goddard, B; Holzer, E B; Höfle, W; Kain, V; Meddahi, M; Radaelli, S; Shaposhnilova, E; Uythoven, J; Valuch, D; Wenninger, J; Zamantzas, C; Gianfelice-Wendt, E

    2012-01-01

    Injection losses are compared for 2010 and 2011 operation. Mitigation techniques which were put in place in 2010 to reduce losses at injection are described. Issues in 2011 operation, their potential improvements and the performance reach for 2012 are shown.

  12. OI Issues: Hearing Loss

    Science.gov (United States)

    Hearing Loss and Osteogenesis Imperfecta Introduction Significant hearing loss has been reported in approximately 50% of people with osteogenesis imperfecta (OI) beginning any time from childhood into middle age. While not ...

  13. Hearing loss and music

    Science.gov (United States)

    ... and how often you are exposed to loud music Headphone use Family history of hearing loss Jobs or activities that increase your chance of hearing loss from music are: Being a musician, sound crew member, or ...

  14. Recurrent pregnancy loss

    DEFF Research Database (Denmark)

    Egerup, Pia; Kolte, A M; Larsen, E C

    2016-01-01

    STUDY QUESTION: Is there a different prognostic impact for consecutive and non-consecutive early pregnancy losses in women with secondary recurrent pregnancy loss (RPL)? SUMMARY ANSWER: Only consecutive early pregnancy losses after the last birth have a statistically significant negative prognostic...... impact in women with secondary RPL. WHAT IS KNOWN ALREADY: The risk of a new pregnancy loss increases with the number of previous pregnancy losses in patients with RPL. Second trimester losses seem to exhibit a stronger negative impact than early losses. It is unknown whether the sequence of pregnancy...... losses plays a role for the prognosis in patients with a prior birth. STUDY DESIGN, SIZE, DURATION: This retrospective cohort study of pregnancy outcome in patients with unexplained secondary RPL included in three previously published, Danish double-blinded placebo-controlled trials of intravenous...

  15. Gibberellin signaling.

    Science.gov (United States)

    Hartweck, Lynn M

    2008-12-01

    This review covers recent advances in gibberellin (GA) signaling. GA signaling is now understood to hinge on DELLA proteins. DELLAs negatively regulate GA response by activating the promoters of several genes including Xerico, which upregulates the abscisic acid pathway which is antagonistic to GA. DELLAs also promote transcription of the GA receptor, GIBBERELLIN INSENSITIVE DWARF 1 (GID1) and indirectly regulate GA biosynthesis genes enhancing GA responsiveness and feedback control. A structural analysis of GID1 provides a model for understanding GA signaling. GA binds within a pocket of GID1, changes GID1 conformation and increases the affinity of GID1 for DELLA proteins. GA/GID1/DELLA has increased affinity for an F-Box protein and DELLAs are subsequently degraded via the proteasome. Therefore, GA induces growth through degradation of the DELLAs. The binding of DELLA proteins to three of the PHYTOCHROME INTERACTING FACTOR (PIF) proteins integrates light and GA signaling pathways. This binding prevents PIFs 3, 4, and 5 from functioning as positive transcriptional regulators of growth in the dark. Since PIFs are degraded in light, these PIFs can only function in the combined absence of light and presence of GA. New analyses suggest that GA signaling evolved at the same time or just after the plant vascular system and before plants acquired the capacity for seed reproduction. An analysis of sequences cloned from Physcomitrella suggests that GID1 and DELLAs were the first to evolve but did not initially interact. The more recently diverging spike moss Selaginella has all the genes required for GA biosynthesis and signaling, but the role of GA response in Selaginella physiology remains a mystery.

  16. Regulation of Hippo signalling by p38 signalling.

    Science.gov (United States)

    Huang, Dashun; Li, Xiaojiao; Sun, Li; Huang, Ping; Ying, Hao; Wang, Hui; Wu, Jiarui; Song, Haiyun

    2016-08-01

    The Hippo signalling pathway has a crucial role in growth control during development, and its dysregulation contributes to tumorigenesis. Recent studies uncover multiple upstream regulatory inputs into Hippo signalling, which affects phosphorylation of the transcriptional coactivator Yki/YAP/TAZ by Wts/Lats. Here we identify the p38 mitogen-activated protein kinase (MAPK) pathway as a new upstream branch of the Hippo pathway. In Drosophila, overexpression of MAPKK gene licorne (lic), or MAPKKK gene Mekk1, promotes Yki activity and induces Hippo target gene expression. Loss-of-function studies show that lic regulates Hippo signalling in ovary follicle cells and in the wing disc. Epistasis analysis indicates that Mekk1 and lic affect Hippo signalling via p38b and wts We further demonstrate that the Mekk1-Lic-p38b cascade inhibits Hippo signalling by promoting F-actin accumulation and Jub phosphorylation. In addition, p38 signalling modulates actin filaments and Hippo signalling in parallel to small GTPases Ras, Rac1, and Rho1. Lastly, we show that p38 signalling regulates Hippo signalling in mammalian cell lines. The Lic homologue MKK3 promotes nuclear localization of YAP via the actin cytoskeleton. Upregulation or downregulation of the p38 pathway regulates YAP-mediated transcription. Our work thus reveals a conserved crosstalk between the p38 MAPK pathway and the Hippo pathway in growth regulation. © The Author (2016). Published by Oxford University Press on behalf of Journal of Molecular Cell Biology, IBCB, SIBS, CAS.

  17. Unpleasant odors increase aversion to monetary losses.

    Science.gov (United States)

    Stancak, Andrej; Xie, Yuxin; Fallon, Nicholas; Bulsing, Patricia; Giesbrecht, Timo; Thomas, Anna; Pantelous, Athanasios A

    2015-04-01

    Loss aversion is the tendency to prefer avoiding losses over acquiring gains of equal nominal values. Unpleasant odors not only influence affective state but have also been shown to activate brain regions similar to those mediating loss aversion. Therefore, we hypothesized a stronger loss aversion in a monetary gamble task if gambles were associated with an unpleasant as opposed to pleasant odor. In thirty human subjects, unpleasant (methylmercaptan), pleasant (jasmine), and neutral (clean air) odors were presented for 4 s. At the same time, uncertain gambles offering an equal chance of gain or loss of a variable amount of money, or a prospect of an assured win were displayed. One hundred different gambles were presented three times, each time paired with a different odor. Loss aversion, risk aversion, and logit sensitivity were evaluated using non-linear fitting of individual gamble decisions. Loss aversion was larger when prospects were displayed in the presence of methylmercaptan compared to jasmine or clean air. Moreover, individual differences in changes in loss aversion to the unpleasant as compared to pleasant odor correlated with odor pleasantness but not with odor intensity. Skin conductance responses to losses during the outcome period were larger when gambles were associated with methylmercaptan compared to jasmine. Increased loss aversion while perceiving an unpleasant odor suggests a dynamic adjustment of loss aversion toward greater sensitivity to losses. Given that odors are biological signals of hazards, such adjustment of loss aversion may have adaptive value in situations entailing threat or danger. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. RHIC BEAM LOSS MONITOR SYSTEM INITIAL OPERATION.

    Energy Technology Data Exchange (ETDEWEB)

    WITKOVER,R.L.; MICHNOFF,R.J.; GELLER,J.M.

    1999-03-29

    The RHIC Beam Loss Monitor (BLM) System is designed to prevent beam loss quenching of the superconducting magnets, and acquire loss data. Four hundred ion chambers are located around the rings to detect losses. The required 8-decade range in signal current is compressed using an RC pre- integrator ahead of a low current amplifier. A beam abort may be triggered if fast or slow losses exceed programmable threshold levels. A micro-controller based VME module sets references and gains and reads trip status for up to 64 channels. Results obtained with the detectors in the RHIC Sextant Test and the prototype electronics in the AGS-to-RHIC (AtR) transfer line are presented along with the present status of the system.

  19. Overview of LHC Beam Loss Measurements

    CERN Document Server

    Dehning, B; Effinger, E; Emery, J; Fadakis, E; Holzer, E B; Jackson, S; Kruk, G; Kurfuerst, C; Marsili, A; Misiowiec, M; Nebot Del Busto, E; Nordt, A; Priebe, A; Roderick, C; Sapinski, M; Zamantzas, C; Grishin, V; Griesmayer, E

    2011-01-01

    The LHC beam loss monitoring system provides measurements with an update rate of 1 Hz and high time resolution data by event triggering. These informations are used for the initiation of beam aborts, fixed displays and the off line analysis. The analysis of fast and localized loss events resulted in the determination of its rate, duration, peak amplitudes, its scaling with intensity, number of bunches and beam energy. The calibration of the secondary shower beam loss signal in respect to the needed beam energy deposition to quench the magnet coil is addressed at 450GeV and 3.5T eV . The adjustment of collimators is checked my measuring the loss pattern and its variation in the collimation regions of the LHC. Loss pattern changes during a fill allow the observation of non typical fill parameters.

  20. Canine hearing loss management.

    Science.gov (United States)

    Scheifele, Lesa; Clark, John Greer; Scheifele, Peter M

    2012-11-01

    Dog owners and handlers are naturally concerned when suspicion of hearing loss arises for their dogs. Questions frequently asked of the veterinarian center on warning signs of canine hearing loss and what can be done for the dog if hearing loss is confirmed. This article addresses warning signs of canine hearing loss, communication training and safety awareness issues, and the feasibility of hearing aid amplification for dogs. Copyright © 2012 Elsevier Inc. All rights reserved.

  1. Transition after Traumatic Loss

    Science.gov (United States)

    Kuban, Caelan

    2011-01-01

    Children experience grief when they suffer the loss of a close relationship. When that loss also traumatizes children, they experience additional emotional reactions. It is important that adults educate themselves and others who deal with children about typical, healthy grief reactions. Following a non-violent loss, the initial reactions of…

  2. Medicines and Bone Loss

    Science.gov (United States)

    Fact Sheet Medici a ne n s d Bone Loss Some types of medicines can cause bone loss, making your bones weak, if used for a long time. Use over a short time ... old bone and replaces it with new bone. Bone loss occurs when old bone breaks down faster than ...

  3. Beam Loss in Linacs

    CERN Document Server

    Plum, M.A.

    2016-01-01

    Beam loss is a critical issue in high-intensity accelerators, and much effort is expended during both the design and operation phases to minimize the loss and to keep it to manageable levels. As new accelerators become ever more powerful, beam loss becomes even more critical. Linacs for H- ion beams, such as the one at the Oak Ridge Spallation Neutron Source, have many more loss mechanisms compared to H+ (proton) linacs, such as the one being designed for the European Spallation Neutron Source. Interesting H- beam loss mechanisms include residual gas stripping, H+ capture and acceleration, field stripping, black-body radiation and the recently discovered intra-beam stripping mechanism. Beam halo formation, and ion source or RF turn on/off transients, are examples of beam loss mechanisms that are common for both H+ and H- accelerators. Machine protection systems play an important role in limiting the beam loss.

  4. Drugs and hair loss.

    Science.gov (United States)

    Patel, Mansi; Harrison, Shannon; Sinclair, Rodney

    2013-01-01

    Hair loss is a common complaint, both in men and women, and use of prescription medications is widespread. When there is a temporal association between the onset of hair loss and commencement of a medication, the medication is commonly thought to have caused the hair loss. However, hair loss and in particular telogen effluvium may occur in response to a number of triggers including fever, hemorrhage, severe illness, stress, and childbirth, and a thorough exclusion of these potential confounders is necessary before the hair loss can be blamed on the medication. Certain medications are known to cause hair loss by a variety of mechanisms including anagen arrest, telogen effluvium, or accentuation of androgenetic alopecia by androgens. Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.

  5. Handbook on loss reserving

    CERN Document Server

    Schmidt, Klaus; Schnaus, Anja

    2016-01-01

    This handbook presents the basic aspects of actuarial loss reserving. Besides the traditional methods, it also includes a description of more recent ones and a discussion of certain problems occurring in actuarial practice, like inflation, scarce data, large claims, slow loss development, the use of market statistics, the need for simulation techniques and the task of calculating best estimates and ranges of future losses. In property and casualty insurance the provisions for payment obligations from losses that have occurred but have not yet been settled usually constitute the largest item on the liabilities side of an insurer's balance sheet. For this reason, the determination and evaluation of these loss reserves is of considerable economic importance for every property and casualty insurer. Actuarial students, academics as well as practicing actuaries will benefit from this overview of the most important actuarial methods of loss reserving by developing an understanding of the underlying stochastic models...

  6. Loss of vision.

    Science.gov (United States)

    Lueck, Christian J

    2010-12-01

    Visual loss is not uncommon and many patients end up seeing neurologists because of it. There is a long list of possible causes but in most patients visual loss is associated with visual field loss. This means that for practical purposes the differential diagnosis can usually be narrowed down to a manageable shortlist by consideration of where in the visual pathway the lesion is likely to be, along with the time course of the visual loss. This article provides a practical approach to the diagnosis and appropriate investigation of such patients, dividing them into four groups: those in whom vision is lost transiently, acutely, subacutely (i.e., days to weeks) and over a longer time frame (months to years). In addition, there is a discussion of those patients in whom visual loss is not obviously accompanied by any visual field loss.

  7. [Genetic hearing loss].

    Science.gov (United States)

    Tanaka-Ouyang, Lei; Marlin, Sandrine; Nevoux, Jérôme

    2017-11-01

    Deafness is the most common sensory disability in developed countries affecting more than 2 births in 1000. Eighty percent of congenital deafness is genetic. Universal newborn hearing screening has been in place since 2012 in France. All genetic hearing losses are not congenital and all congenital hearing losses are not genetic. Genetic hearing loss may be syndromic (associated with other symptoms) (10 %) or non-syndromic (isolated) (90 %). Hearing loss may initially be the only symptom of syndromic deafness. A genetic origin can be diagnosed and must therefore be evoked systematically even in the adult. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  8. Hearing Loss in Children: Types of Hearing Loss

    Science.gov (United States)

    ... Hearing Loss Homepage Facts Noise-Induced Hearing Loss Genetics of Hearing Loss Screening & Diagnosis Types of Hearing Loss About Sound Treatment & Intervention Services Learning Language Bacterial Meningitis Studies Data & Statistics EHDI Annual Data 2015 ...

  9. Prosocial Signalling

    DEFF Research Database (Denmark)

    Kahsay, Goytom Abraha

    In contrast to the standard economic theory predictions, it seems clear that people do spend their time and resource to benefit others. Many lab and field experiment studies show that people display prosocial preferences such as altruism, reciprocity and conditional cooperation, fairness, etc...... signalling can cause reverse price reactions resembling the crowding-out of pre-existing motives for prosocial behavior seen in situations of volunteering and charitable giving. Using a unique combination of questionnaire and purchase panel data, it presents evidence of such reputation-driven reverse price...

  10. Loss muinasjuturaamatust / Agu Veetamm

    Index Scriptorium Estoniae

    Veetamm, Agu, 1953-

    2004-01-01

    Ballindaloch on üks väheseid Shoti losse, kus omanikud aastaringselt elavad. 450 aastat on loss kuulunud Macpherson-Grantide suguvõsale. Praegu on lossi omanikuks Clare Nancy Macpherson-Grant Russell, kelle kujundatud on kiviktaimla ja rosaarium. Lossi ajaloost, omanikest, ümberehitustest, ringkäigust lossis, pargist. 14 ill

  11. Experimental circulation loss study

    OpenAIRE

    Lund, Sigurd

    2013-01-01

    Circulation losses could occur during any operation that involves pumping into a well. As of today, it is recognized as one of the most costly drilling problems. In some situation it might be hard to stop, and usually takes precious rig time to deal with the problem. In order to mitigate the risk of circulation loss solid pa...

  12. Grief following homicidal loss

    NARCIS (Netherlands)

    van Denderen, Mariëtte

    2017-01-01

    People confronted with homicidal loss have to cope with separation distress, related to their loss, and traumatic distress, associated with the circumstances surrounding the death. These reactions are related to complicated grief and posttraumatic stress symptoms. Based on a questionnaire study

  13. Hearing Loss and Cytomegalovirus.

    Science.gov (United States)

    Strauss, Melvin

    1997-01-01

    Cytomegalovirus is the most common cause of congenital virally induced hearing loss. Maternal infection is most often asymptomatic as is the infection in the newborn. Hearing loss occurs in both clinically apparent infection and in the asymptomatic infection. Current methods of detection, treatment, and prevention and research efforts are…

  14. Weight Loss Surgery

    Science.gov (United States)

    Weight loss surgery helps people with extreme obesity to lose weight. It may be an option if you cannot lose weight through diet and exercise or have serious health problems caused by obesity. There are different types of weight loss surgery. They often limit the amount of food ...

  15. Proven Weight Loss Methods

    Science.gov (United States)

    Fact Sheet Proven Weight Loss Methods What can weight loss do for you? Losing weight can improve your health in a number of ways. ... you feel better. There are proven ways to lose weight. You can find what works for you. Research ...

  16. Non pecuniary losses

    NARCIS (Netherlands)

    S.D. Lindenbergh (Siewert); P.M. Kippersluis (Peter)

    2009-01-01

    textabstractNon pecuniary losses can be characterized as losses that are suffered by damaging goods or interests which have in themselves no economic price or value on a financial market. Examples are damage to goods with a primarily sentimental value, such as an album of wedding photos, pain and

  17. [Inner Ear Hearing Loss].

    Science.gov (United States)

    Hesse, G

    2016-06-01

    Hearing loss is one of the most dominant handicaps in modern societies, which additionally very often is not realized or not admitted. About one quarter of the general population suffers from inner ear hearing loss and is therefore restricted in communicational skills. Demographic factors like increasing age play an important role as well as environmental influences and an increasing sound and noise exposure especially in leisure activities. Thus borders between a "classical" presbyacusis - if it ever existed - and envirionmentally induced hearing loss disappear. Today restrictions in hearing ability develop earlier in age but at the same time they are detected and diagnosed earlier. This paper can eventually enlighten the wide field of inner ear hearing loss only fragmentarily; therefore mainly new research, findings and developments are reviewed. The first part discusses new aspects of diagnostics of inner ear hearing loss and different etiologies. © Georg Thieme Verlag KG Stuttgart · New York.

  18. Noise-Induced Hearing Loss

    Science.gov (United States)

    ... Hearing Loss Homepage Facts Noise-Induced Hearing Loss Genetics of Hearing Loss Screening & Diagnosis Types of Hearing Loss About Sound Treatment & Intervention Services Learning Language Bacterial Meningitis Studies Data & Statistics EHDI Annual Data 2015 ...

  19. New Treatments for Hair Loss.

    Science.gov (United States)

    Vañó-Galván, S; Camacho, F

    2017-04-01

    The treatment of hair loss is an important part of clinical dermatology given the prevalence of the problem and great impact on patients' quality of life. Many new treatments have been introduced in recent years. This review summarizes the main ones in 4 groups: a) For androgenetic alopecia, we discuss new excipients for oral minoxidil, dutasteride, and finasteride as well as new forms of topical application; prostaglandin agonists and antagonists; low-level laser therapy; and regenerative medicine with Wnt signaling activators and stem cell therapy. b) For alopecia areata, Janus kinase inhibitors are reviewed. c) For frontal fibrosing alopecia, we discuss the use of antiandrogens and, for some patients, pioglitazone. d) Finally, we mention new robotic devices for hair transplant procedures and techniques for optimal follicular unit extraction. Copyright © 2016 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

  20. Beam Loss Monitors at LHC

    CERN Document Server

    Dehning, B.

    2016-01-01

    One of the main functions of the LHC beam loss measurement system is the protection of equipment against damage caused by impacting particles creating secondary showers and their energy dissipation in the matter. Reliability requirements are scaled according to the acceptable consequences and the frequency of particle impact events on equipment. Increasing reliability often leads to more complex systems. The downside of complexity is a reduction of availability; therefore, an optimum has to be found for these conflicting requirements. A detailed review of selected concepts and solutions for the LHC system will be given to show approaches used in various parts of the system from the sensors, signal processing, and software implementations to the requirements for operation and documentation.

  1. Diphtheria and hearing loss.

    OpenAIRE

    Schubert, C. R.; Cruickshanks, K. J.; Wiley, T. L.; Klein, R.; Klein, B E; Tweed, T. S.

    2001-01-01

    OBJECTIVE: To determine if infectious diseases usually experienced in childhood have an effect on hearing ability later in life. METHODS: The Epidemiology of Hearing Loss Study (N = 3,753) is a population-based study of age-related hearing loss in adults aged 48 to 92 years in Beaver Dam, Wisconsin. As part of this study, infectious disease history was obtained and hearing was tested using pure-tone audiometry. Hearing loss was defined as a pure-tone average of thresholds at 500 Hz, 1,000 Hz,...

  2. Saccadic entropy of head impulses in acute unilateral vestibular loss

    OpenAIRE

    Hsieh, Li-Chun; Lin, Hung-Ching; Lee, Guo-She

    2016-01-01

    To evaluate the complexity of vestibular–ocular reflex (VOR) in patients with acute unilateral vestibular loss (AUVL) via entropy analysis of head impulses. Methods: Horizontal head impulse test (HIT) with high-velocity alternating directions was used to evaluate 12 participants with AUVL and 16 healthy volunteers. Wireless electro-oculography and electronic gyrometry were used to acquire eye positional signals and head velocity signals. The eye velocity signals were then obtained through ...

  3. Understanding Grief and Loss

    Science.gov (United States)

    ... time. The grieving person’s age and gender The life history of the person who is grieving, including previous experiences with loss The grieving person’s personality and coping style The support available from friends and family The ...

  4. Coping with Memory Loss

    Science.gov (United States)

    ... professional. What Causes Memory Loss? Anything that affects cognition—the process of thinking, learning, and remembering—can ... Stages of Alzheimer's Disease More in Consumer Updates Animal & Veterinary Children's Health Cosmetics Dietary Supplements Drugs Food ...

  5. Hearing loss - infants

    Science.gov (United States)

    ... brain after birth, such as meningitis or measles Problems with the structure of the inner ear Tumors Central hearing loss results from damage to the auditory nerve itself, or the brain pathways that lead ...

  6. Hearing Loss: Screening Newborns

    Science.gov (United States)

    ... of this page please turn JavaScript on. Feature: Hearing Loss Screening Newborns Past Issues / Spring 2015 Table ... deafness, which account for most cases. Screening Newborns' Hearing Now Standard In 1993, children born in the ...

  7. Weight Loss & Acute Porphyria

    Science.gov (United States)

    ... APF You are here Home Diet and Nutrition Weight loss & acute Porphyria Being overweight is a particular problem ... of carbohydrate and energy in an effort to lose weight can worsen these diseases. Severe acute attacks have ...

  8. Female Pattern Hair Loss

    Science.gov (United States)

    ... of hormone imbalance, such as excess facial or body hair, a hormone evaluation should be done. Hormonal changes ... any sudden physical or psychological stress to the body. These types of hair loss are "Telogen Effluvium" and are usually temporary. ...

  9. Muscle function loss

    Science.gov (United States)

    ... myelopathy), or brain damage ( stroke or other brain injury) The loss of muscle function after these types of events can be ... Periodic paralysis Focal nerve injury Polio Spinal cord injury Stroke

  10. Hair Loss Myths.

    Science.gov (United States)

    DiMarco, Gabriella; McMichael, Amy

    2017-07-01

    INTRODUCTION: Hair loss is a common complaint seen in dermatology clinics. From frustration and attempts at self-help, patients with hair loss may present to the dermatologist with false beliefs, or myths, about the causes of their condition and what treatments are effective. METHODS: We identified 12 common myths about hair loss, categorized as myths about minoxidil treatment, vitamin and mineral supplements, natural topical treatments, and hair care practices. We performed a PubMed search to find evidence to support or refute each myth. RESULTS: We found that there is little evidence to support many of these common hair loss myths. In some cases, randomized controlled trials have investigated the effects of particular therapies and point to the effectiveness of certain hair loss treatments. DISCUSSION: In many cases, there have not been sufficient randomized controlled trials to evaluate the effect of different therapies and hair care practices on hair loss. It is best to guide patients toward treatments with a long track record of efficacy and away from those where little is known scientifically. J Drugs Dermatol. 2017;16(7):690-694..

  11. Atmosphere Impact Losses

    Science.gov (United States)

    Schlichting, Hilke E.; Mukhopadhyay, Sujoy

    2018-02-01

    Determining the origin of volatiles on terrestrial planets and quantifying atmospheric loss during planet formation is crucial for understanding the history and evolution of planetary atmospheres. Using geochemical observations of noble gases and major volatiles we determine what the present day inventory of volatiles tells us about the sources, the accretion process and the early differentiation of the Earth. We further quantify the key volatile loss mechanisms and the atmospheric loss history during Earth's formation. Volatiles were accreted throughout the Earth's formation, but Earth's early accretion history was volatile poor. Although nebular Ne and possible H in the deep mantle might be a fingerprint of this early accretion, most of the mantle does not remember this signature implying that volatile loss occurred during accretion. Present day geochemistry of volatiles shows no evidence of hydrodynamic escape as the isotopic compositions of most volatiles are chondritic. This suggests that atmospheric loss generated by impacts played a major role during Earth's formation. While many of the volatiles have chondritic isotopic ratios, their relative abundances are certainly not chondritic again suggesting volatile loss tied to impacts. Geochemical evidence of atmospheric loss comes from the {}3He/{}^{22}Ne, halogen ratios (e.g., F/Cl) and low H/N ratios. In addition, the geochemical ratios indicate that most of the water could have been delivered prior to the Moon forming impact and that the Moon forming impact did not drive off the ocean. Given the importance of impacts in determining the volatile budget of the Earth we examine the contributions to atmospheric loss from both small and large impacts. We find that atmospheric mass loss due to impacts can be characterized into three different regimes: 1) Giant Impacts, that create a strong shock transversing the whole planet and that can lead to atmospheric loss globally. 2) Large enough impactors (m_{cap} ≳ √{2

  12. Processing the telephone speech signal for the hearing impaired.

    Science.gov (United States)

    Terry, M; Bright, K; Durian, M; Kepler, L; Sweetman, R; Grim, M

    1992-04-01

    Speech intelligibility scores from 16 subjects with sensorineural hearing loss were evaluated using a digitized version of the California Consonant Test that was presented via headphones through a 300 to 3000 Hz bandpass filter to simulate the telephone band. Each subject was tested with an unprocessed signal that was frequency-equalized to compensate for the individual's hearing loss, and a signal that was equalized and compressed by the use of a compressor compression technique. Subjects were tested at three sound pressure levels above a pure-tone average threshold for frequencies 1 and 2 kHz. Two digital signal processing techniques designed to compensate for high-frequency hearing loss were examined: frequency domain processing and time domain processing. Frequency domain involved modification of the short-term spectrum obtained through a fast Fourier transform, whereas time domain processing involved passing the signal through a bank of finite impulse response filters. Both techniques showed significant intelligibility improvements (15-30%). In a second experiment, 16 additional subjects with high-frequency hearing loss compared an amplified telephone signal to three processed signals: (1) 6 dB per octave emphasis; (2) a signal frequency equalized for their hearing loss; and (3) a signal that was equalized for their hearing loss and was compressed according to their uncomfortable loudness levels. Most subjects preferred the signal with the 6 dB per octave emphasis.

  13. Measurements of Beam Ion Loss from the Compact Helical System

    Energy Technology Data Exchange (ETDEWEB)

    D. S. Darrow, M. Isobe, Takashi Kondo, M. Sasao, and the CHS Group National Institute for Fusion Science, Toki, Gifu, Japan

    2010-02-03

    Beam ion loss from the Compact Helical System (CHS) has been measured with a scintillator-type probe. The total loss to the probe, and the pitch angle and gyroradius distributions of that loss, have been measured as various plasma parameters were scanned. Three classes of beam ion loss were observed at the probe position: passing ions with pitch angles within 10o of those of transition orbits, ions on transition orbits, and ions on trapped orbits, typically 15o or more from transition orbits. Some orbit calculations in this geometry have been performed in order to understand the characteristics of the loss. Simulation of the detector signal based upon the following of orbits from realistic beam deposition profiles is not able to reproduce the pitch angle distribution of the losses measured. Consequently it is inferred that internal plasma processes, whether magnetohydrodynamic modes, radial electric fields, or plasma turbulence, move previously confined beam ions to transition orbits, resulting in their loss.

  14. Hedgehog signaling in the stomach.

    Science.gov (United States)

    Konstantinou, Daniel; Bertaux-Skeirik, Nina; Zavros, Yana

    2016-12-01

    The Hedgehog (Hh) signaling pathway not only plays a key part in controlling embryonic development, but in the adult stomach governs important cellular events such as epithelial cell differentiation, proliferation, gastric disease, and regeneration. In particular, Sonic Hedgehog (Shh) signaling has been well studied for its role in gastric physiology and pathophysiology. Shh is secreted from the gastric parietal cells and contributes to the regeneration of the epithelium in response to injury, or the development of gastritis during Helicobacter pylori infection. Dysregulation of the Shh signaling pathway leads to the disruption of gastric differentiation, loss of gastric acid secretion and the development of cancer. In this chapter, we will review the most recent findings that reveal the role of Shh as a regulator of gastric physiology, regeneration, and disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Weight loss update.

    Science.gov (United States)

    1996-11-01

    Unwanted weight loss in people with HIV can be caused by one or more factors simultaneously. A two-pronged approach that addresses the factors causing weight loss and malnutrition, and maintaining or gaining weight is critical. Many opportunistic infections (OIs) can cause diarrhea, but both the drugs used to treat diarrhea and the infections themselves can contribute to weight loss. Lactose intolerance is a common cause of diarrhea in people living with HIV. Because some of the drugs used to treat HIV and OIs are packaged with lactose, it may be necessary to replace the enzymes needed to break down lactose. Appetite loss may also contribute to wasting, and the lack of nutrients from a lost appetite can tax the body and further aggravate the problem. Appetite stimulants, vitamin supplements, or weight gain products that promote the building of protein are possible treatment options. Lean body mass production may require the use of anabolic (protein building) steroids or testosterone replacement therapy. Another wasting intervention option involves recombinant human growth hormone (rHGH), however, unsubstantiated safety concerns have arisen on the use of rHGH, and may require increased monitoring. Finally, counteracting weight loss may require adjusting the elevated levels of an immune system chemical called tumor necrosis factor (TNF) with thalidomide. Because of thalidomide's association with birth defects, sexually active heterosexual women should be advised to use multiple contraceptive mechanisms.

  16. Congenital sensorineural hearing loss

    Energy Technology Data Exchange (ETDEWEB)

    Mafee, M.F.; Selis, J.E.; Yannias, D.A.; Valvassori, G.E.; Pruzansky, S.; Applebaum, E.L.; Capek, V.

    1984-02-01

    The ears of 47 selected patients with congenital sensorineural hearing loss were examined with complex-motion tomography. The patients were divided into 3 general categories: those with a recognized syndrome, those with sensorineural hearing loss unrelated to any known syndrome, and those with microtia. A great variety of inner ear anomalies was detected, but rarely were these characteristic of a particular clinical entity. The most common finding was the Mondini malformation or one of its variants. Isolated dysplasia of the internal auditory canal or the vestibular aqueduct may be responsible for sensorineural hearing loss in some patients. Patients with microtia may also have severe inner ear abnormalities despite the fact that the outer and inner ears develop embryologically from completely separate systems.

  17. Weight Loss Nutritional Supplements

    Science.gov (United States)

    Eckerson, Joan M.

    Obesity has reached what may be considered epidemic proportions in the United States, not only for adults but for children. Because of the medical implications and health care costs associated with obesity, as well as the negative social and psychological impacts, many individuals turn to nonprescription nutritional weight loss supplements hoping for a quick fix, and the weight loss industry has responded by offering a variety of products that generates billions of dollars each year in sales. Most nutritional weight loss supplements are purported to work by increasing energy expenditure, modulating carbohydrate or fat metabolism, increasing satiety, inducing diuresis, or blocking fat absorption. To review the literally hundreds of nutritional weight loss supplements available on the market today is well beyond the scope of this chapter. Therefore, several of the most commonly used supplements were selected for critical review, and practical recommendations are provided based on the findings of well controlled, randomized clinical trials that examined their efficacy. In most cases, the nutritional supplements reviewed either elicited no meaningful effect or resulted in changes in body weight and composition that are similar to what occurs through a restricted diet and exercise program. Although there is some evidence to suggest that herbal forms of ephedrine, such as ma huang, combined with caffeine or caffeine and aspirin (i.e., ECA stack) is effective for inducing moderate weight loss in overweight adults, because of the recent ban on ephedra manufacturers must now use ephedra-free ingredients, such as bitter orange, which do not appear to be as effective. The dietary fiber, glucomannan, also appears to hold some promise as a possible treatment for weight loss, but other related forms of dietary fiber, including guar gum and psyllium, are ineffective.

  18. Recurrent Pregnancy Loss

    Directory of Open Access Journals (Sweden)

    Véronique Piroux

    1997-01-01

    Full Text Available Antiphospholipid antibodies (APA are associated with thrombosis, thrombocytopenia and fetal loss but they occur in a variety of diseases. Despite many efforts, a correlation between the specificity of particular subgroups of APA and particular clinical situations remains to be established. The antigens at the origin of APA remain to be identified. We discuss here the possible links between cell apoptosis or necrosis, leading to plasma membrane alterations, and the occurrence of APA in response to sustained stimulation. The pathogenic potential of APA is also considered with respect to recurrent pregnancy loss.

  19. High flip angle imaging of metallic stents: Implications for MR angiography and intraluminal signal interpretation

    NARCIS (Netherlands)

    Brück, E.H.; van Holten, J.; Wielopolski, P.; Pattynama, P.M.T.; van Dijk, L.C.

    2003-01-01

    Intraluminal stent signal characterization by MRI is generally hampered by signal loss from the metallic stent material. This signal loss is related to magnetic susceptibility and RF shielding. Even when stent materials with low magnetic susceptibility are used, RF shielding can still be

  20. Side Effects: Hair Loss (Alopecia)

    Science.gov (United States)

    Hair loss, also called alopecia, is a side effect of cancer treatments, such as chemotherapy and radiation therapy. Learn how to cope with and manage hair loss. Listen to tips from others who have experienced hair loss.

  1. Regulator Loss Functions and Hierarchical Modeling for Safety Decision Making.

    Science.gov (United States)

    Hatfield, Laura A; Baugh, Christine M; Azzone, Vanessa; Normand, Sharon-Lise T

    2017-07-01

    Regulators must act to protect the public when evidence indicates safety problems with medical devices. This requires complex tradeoffs among risks and benefits, which conventional safety surveillance methods do not incorporate. To combine explicit regulator loss functions with statistical evidence on medical device safety signals to improve decision making. In the Hospital Cost and Utilization Project National Inpatient Sample, we select pediatric inpatient admissions and identify adverse medical device events (AMDEs). We fit hierarchical Bayesian models to the annual hospital-level AMDE rates, accounting for patient and hospital characteristics. These models produce expected AMDE rates (a safety target), against which we compare the observed rates in a test year to compute a safety signal. We specify a set of loss functions that quantify the costs and benefits of each action as a function of the safety signal. We integrate the loss functions over the posterior distribution of the safety signal to obtain the posterior (Bayes) risk; the preferred action has the smallest Bayes risk. Using simulation and an analysis of AMDE data, we compare our minimum-risk decisions to a conventional Z score approach for classifying safety signals. The 2 rules produced different actions for nearly half of hospitals (45%). In the simulation, decisions that minimize Bayes risk outperform Z score-based decisions, even when the loss functions or hierarchical models are misspecified. Our method is sensitive to the choice of loss functions; eliciting quantitative inputs to the loss functions from regulators is challenging. A decision-theoretic approach to acting on safety signals is potentially promising but requires careful specification of loss functions in consultation with subject matter experts.

  2. Blindness and vision loss

    Science.gov (United States)

    ... have low vision, you may have trouble driving, reading, or doing small tasks such as sewing or ... lost vision. You should never ignore vision loss, thinking it will get better. Contact an ... A.D.A.M.'s editorial policy , editorial process and privacy policy . A.D.A.M. is ...

  3. Experimental circulation loss study

    OpenAIRE

    Lund, Sigurd

    2013-01-01

    Master's thesis in Petroleum engineering Circulation losses could occur during any operation that involves pumping into a well. As of today, it is recognized as one of the most costly drilling problems. In some situation it might be hard to stop, and usually takes precious rig time to deal with the problem. In order to mitigate the risk...

  4. Biologicals and bone loss

    NARCIS (Netherlands)

    Krieckaert, C.L.M.; Lems, W.F.

    2012-01-01

    Inflammatory joint diseases are associated with extra-articular side effects including bone involvement.There is an increased risk of osteoporotic fractures. The pathogeneses of local and generalized bone loss share a common pathway. Early and active rheumatoid arthritis is associated with

  5. Degreaser Reduces Solvent Loss

    Science.gov (United States)

    Du Fresne, E. R.

    1985-01-01

    Escape of solvent minimized by second cooling coil. Degreaser suppresses solvent-vapor loss through parts-basket dragout and air drafts. Within C02 blanket, convection repeatedly exposes C02/solvent mixture to cold spot created by C02 coil. Solvent vapor condenses, then runs down via through to cold tank. This small expenditure of C02 minimizes health and environmental hazards.

  6. Heat loss from Buildings

    DEFF Research Database (Denmark)

    Karlsson, Kenneth; Næraa, Rikke

    1997-01-01

    Determination of heat loss coefficients for buildings in Denmark. The coefficient are determined for 15 building groups and 3 year intervals. They are based on the BBR-registre and assumptions of U-values(W/K*m2)and computed in a simple spreed sheet model.The results are used in the REVEILLE...

  7. Responding to Amphibian Loss

    NARCIS (Netherlands)

    Mendelson III, J.R.; Lips, K.R.; Gagliardo, R.W.; Rabb, G.B.; Collins, J.P.; Diffendorfer, J.E.; Daszak, P.; Ibáñez D., R.; Zippel, K.C.; Lawson, D.P.; Wright, K.M.; Stuart, S.N.; Gascon, C.; da Silva, H.R.; Burrowes, P.A.; Joglar, R.L.; La Marca, E.; Lötters, S.; du Preez, L.H.; Weldon, C.; Hyatt, A.; Rodriguez-Mahecha, J.V.; Hunt, S.; Robertson, H.; Lock, B.; Raxworthy, C.J.; Frost, D.R.; Lacy, R.C.; Alford, R.A.; Campbell, J.A.; Parra-Olea, G.; Bolaños, F.; Calvo Domingo, J.J.; Halliday, T.; Murphy, J.B.; Wake, M.H.; Coloma, L.A.; Kuzmin, S.L.; Price, M.S.; Howell, K.M.; Lau, M.; Pethiyagoda, R.; Boone, M.; Lannoo, M.J.; Blaustein, A.R.; Dobson, A.; Griffiths, R.A.; Crump, M.L.; Wake, D.B.; Brodie Jr, E.D.

    2006-01-01

    In their Policy Forum "Confronting amphibian declines and extinctions" (7 July, p. 48), J. R. Mendelson III and colleagues offer a strategy for "stopping" the widespread losses of frogs, toads, and salamanders. Disease research and captive breeding figure prominently in their call for action.

  8. Measuring Gearbox Torque Loss

    Science.gov (United States)

    Schmidt, L. F.

    1986-01-01

    Accuracy increased by measuring small torque differences directly. Input and output torques are balanced by mechanical linkage in transmission-testing apparatus. Force applied to load cell proportional to frictional torque loss in transmission. Apparatus measures portion of input torque lost to friction in automotive transmissions or other gearbox. Apparatus more sensitive than previous measuring systems.

  9. Transmitter Signal Measurements, Task 5C Report

    Science.gov (United States)

    Horton, Kent; Eppic, Brian; Huffman, Mitch; White, Harrison

    2005-01-01

    Signal Measurements were obtained on four (4) different airport systems. Systems measured were Localizer (LOC), Very High Frequency Communication, (VHF), Glideslope, (G/S), and Global Positioning System (GPS). The task calls for path loss measurements to be taken at Hartsfield-Jackson International Airport (ATL) and one smaller airport which was Greenville/ Spartanburg Airport (GSP) to determine relative signal strengths on the airport properties.

  10. LHC Beam Loss Monitor System Design

    Science.gov (United States)

    Dehning, B.; Ferioli, G.; Friesenbichler, W.; Gschwendtner, E.; Koopman, J.

    2002-12-01

    At the LHC a beam loss system will be installed for continuous surveillance of particle losses. The system is designed to prevent hardware destructions, to avoid magnet coil quenches and to provide quantitative loss values. Over 3000 ionization chambers will be used to initiate the beam abort if the loss rates exceed the quench levels. The time and beam energy dependent quench levels require the acquisition of chamber currents in the range from 50 pA to 0.5 mA and an update of the values every 89 μs. The acquisition and control electronics will consist of a front end electronics near (< 400 m) to the ionization chambers and a threshold controller in the surface buildings. The front end will include a charge balance converter, a counter and multiplexer part. The charge balance converter is most suiteable to cover the large dynamic range. The introduced error is smaller than few % in the required dynamic range. Six channels will be transmitted over one cable of up to 3 km length. The threshold controller will issue warnings and dump signals depending on the beam energy and the loss durations.

  11. Father Loss and Child Telomere Length.

    Science.gov (United States)

    Mitchell, Colter; McLanahan, Sara; Schneper, Lisa; Garfinkel, Irv; Brooks-Gunn, Jeanne; Notterman, Daniel

    2017-08-01

    Father loss during childhood has negative health and behavioral consequences, but the biological consequences are unknown. Our goal was to examine how father loss (because of separation and/or divorce, death, or incarceration) is associated with cellular function as estimated by telomere length. Data come from the 9-year follow-up of the Fragile Families and Child Wellbeing Study, a birth cohort study of children in 20 large American cities (N = 2420). Principal measures are as follows: salivary telomere length (sTL), mother reports of father loss, and polymorphisms in genes related to serotonergic and dopaminergic signaling. At 9 years of age, children with father loss have significantly shorter telomeres (14% reduction). Paternal death has the largest association (16%), followed by incarceration (10%), and separation and/or divorce (6%). Changes in income partially mediate these associations (95% mediation for separation and/or divorce, 30% for incarceration, and 25% for death). Effects are 40% greater for boys and 90% greater for children with the most reactive alleles of the serotonin transporter genes when compared with those with the least reactive alleles. No differences were found by age at father loss or a child's race/ethnicity. Father loss has a significant association with children's sTL, with the death of a father showing the largest effect. Income loss explains most of the association between child sTL and separation and/or divorce but much less of the association with incarceration or death. This underscores the important role of fathers in the care and development of children and supplements evidence of the strong negative effects of parental incarceration. Copyright © 2017 by the American Academy of Pediatrics.

  12. Understanding Loss Deductions for Timber

    Science.gov (United States)

    John Greene; Michael Jacobson

    1998-01-01

    Forestland owners whose timber has been destroyed may be eligible to take a deduction for the loss on their federal income tax. The loss must be physical in nature and caused by an identifiable event or combination of events that has run its course. There are two types of losses from natural events. Casualty losses are sudden, unexpected, and unusual - as from a fire...

  13. Individual Hearing Loss

    Directory of Open Access Journals (Sweden)

    Sébastien Santurette

    2016-06-01

    Full Text Available It is well-established that hearing loss does not only lead to a reduction of hearing sensitivity. Large individual differences are typically observed among listeners with hearing impairment in a wide range of suprathreshold auditory measures. In many cases, audiometric thresholds cannot fully account for such individual differences, which make it challenging to find adequate compensation strategies in hearing devices. How to characterize, model, and compensate for individual hearing loss were the main topics of the fifth International Symposium on Auditory and Audiological Research (ISAAR, held in Nyborg, Denmark, in August 2015. The following collection of papers results from some of the work that was presented and discussed at the symposium.

  14. Decisions under unpredictable losses

    Directory of Open Access Journals (Sweden)

    Ali Ahmed

    2007-10-01

    Full Text Available An experimental test of the descriptive adequacy of the extit{restated diversification principle} is presented. The principle postulates that risk-averse utility maximizers will pool risks for their mutual benefit, even if information is missing about the probabilities of losses. It is enough for people to assume that they face equal risks when they pool risks. The results of the experiment support the principle.

  15. Human Hearing Loss

    OpenAIRE

    Ware, Stacy Lee

    2014-01-01

    Hearing loss affects as much as 5% of the global human population and its negative consequences, often exacerbated by cultural bias or distributive injustice, include delayed cognitive and language development, learning deficits and poor academic performance, chronic unemployment and dependency, poverty, elevated risk of harm and poor health. This paper is based on a review of the academic literature as well as other credible published resources to identify the principal causes of hearing los...

  16. ADT fast losses MD

    CERN Document Server

    Priebe, A; Dehning, B; Redaelli, S; Salvachua Ferrando, BM; Sapinski, M; Solfaroli Camillocci, M; Valuch, D

    2013-01-01

    The fast beam losses in the order of 1 ms are expected to be a potential major luminosity limitation for higher beam energies after the LHC long shutdown (LS1). Therefore a Quench Test is planned in the winter 2013 to estimate the quench limit in this timescale and revise the current models. This experiment was devoted to determination the LHC Transverse Damper (ADT) as a system for fast losses induction. A non-standard operation of the ADT was used to develop the beam oscillation instead of suppressing them. The sign flip method had allowed us to create the fast losses within several LHC turns at 450 GeV during the previous test (26th March 2012). Thus, the ADT could be potentially used for the studies of the UFO ("Unidentied Falling Object") impact on the cold magnets. Verification of the system capability and investigations of the disturbed beam properties were the main objectives of this MD. During the experiment, the pilot bunches of proton beam were excited independently in the horizontal and vertical ...

  17. EPICS communication loss management

    Science.gov (United States)

    Hill, J. O.

    1994-12-01

    In a distributed control system there are multiple processors interconnected by a communications media such as a LAN. Plant I/O points are often divided between these processors according to the number of points that a processor can promptly service and according to processor locations which minimize field wiring. A robust distributed control system should properly respond to temporary loss of communication with any portion of the system. This temporary loss could be caused by hardware or software failures or it could be caused by reconfiguring or rebooting other portions of the system. For the Experimental Physics and Industrial Control System we have handled these temporary outages consistently and reliably. This capability makes it possible for distributed functions such as loop closure, sequencing, archiving, or operator consoles to take proper action at the beginning and end of the loss of communication with another part of the system. The control system continues to function in a degraded mode while some of its subsystems are not responding and resumes normal operation once a subsystem is restored.

  18. Continuous-time signals

    CERN Document Server

    Shmaliy, Yuriy

    2006-01-01

    Gives a modern description of continuous-time deterministic signals Signal formation techniquesTime vs. frequency and frequency vs. time analysisCorrelation and energy analysisNarrowband signals and sampling.

  19. Basic digital signal processing

    CERN Document Server

    Lockhart, Gordon B

    1985-01-01

    Basic Digital Signal Processing describes the principles of digital signal processing and experiments with BASIC programs involving the fast Fourier theorem (FFT). The book reviews the fundamentals of the BASIC program, continuous and discrete time signals including analog signals, Fourier analysis, discrete Fourier transform, signal energy, power. The text also explains digital signal processing involving digital filters, linear time-variant systems, discrete time unit impulse, discrete-time convolution, and the alternative structure for second order infinite impulse response (IIR) sections.

  20. Signal propagation in nerve fiber

    Science.gov (United States)

    Zayko, Yuriy N.

    2007-05-01

    In this paper the problem of signal propagation in nerve fiber is considered. Ohm losses and heat processes were taken into account. These permit to combine the two stages (metabolic and non-metabolic) of propagation and Na + and K + ions transmission through cell membrane due propagation. Electrodynamics of nerve fiber with losses is described by telegraph equations. Heat processes in fiber are described by an equation of entropy transfer. Ion motion at metabolic stage against the electro-chemical potential is described by negative conductance, responsible for the escape flow. The running- wave-type solutions of these equations are studied. An integral and an explicit solution of the given system are obtained. The solution represented by a series of quasi-harmonic pulses is investigated numerically. This proves the applicability of telegraph equation to the problem considered. Different types of solitary waves corresponding to various types of conductivity are also investigated.

  1. Compressed Domain Packet Loss Concealment of Sinusoidally Coded Speech

    DEFF Research Database (Denmark)

    Rødbro, Christoffer A.; Christensen, Mads Græsbøll; Andersen, Søren Vang

    2003-01-01

    We consider the problem of packet loss concealment for voice over IP (VoIP). The speech signal is compressed at the transmitter using a sinusoidal coding scheme working at 8 kbit/s. At the receiver, packet loss concealment is carried out working directly on the quantized sinusoidal parameters......, based on time-scaling of the packets surrounding the missing ones. Subjective listening tests show promising results indicating the potential of sinusoidal speech coding for VoIP....

  2. Zinc Signal in Brain Diseases

    Directory of Open Access Journals (Sweden)

    Stuart D. Portbury

    2017-11-01

    Full Text Available The divalent cation zinc is an integral requirement for optimal cellular processes, whereby it contributes to the function of over 300 enzymes, regulates intracellular signal transduction, and contributes to efficient synaptic transmission in the central nervous system. Given the critical role of zinc in a breadth of cellular processes, its cellular distribution and local tissue level concentrations remain tightly regulated via a series of proteins, primarily including zinc transporter and zinc import proteins. A loss of function of these regulatory pathways, or dietary alterations that result in a change in zinc homeostasis in the brain, can all lead to a myriad of pathological conditions with both acute and chronic effects on function. This review aims to highlight the role of zinc signaling in the central nervous system, where it may precipitate or potentiate diverse issues such as age-related cognitive decline, depression, Alzheimer’s disease or negative outcomes following brain injury.

  3. Female pattern hair loss

    Directory of Open Access Journals (Sweden)

    Archana Singal

    2013-01-01

    Full Text Available Female pattern hair loss (FPHL is a common cause of hair loss in women characterized by diffuse reduction in hair density over the crown and frontal scalp with retention of the frontal hairline. Its prevalence increases with advancing age and is associated with significant psychological morbidity. The pathophysiology of FPHL is still not completely understood and seems to be multifactorial. Although androgens have been implicated, the involvement of androgen-independent mechanisms is evident from frequent lack of clinical or biochemical markers of hyperandrogenism in affected women. The role of genetic polymorphisms involving the androgen and estrogen receptors is being increasingly recognized in its causation and predicting treatment response to anti-androgens. There are different clinical patterns and classifications of FPHL, knowledge of which facilitates patient management and research. Chronic telogen effluvium remains as the most important differential diagnosis. Thorough history, clinical examination, and evaluation are essential to confirm diagnosis. Patients with clinical signs of androgen excess require assessment of biochemical parameters and imaging studies. It is prudent to screen the patients for metabolic syndrome and cardiovascular risk factors. The treatment comprises medical and/or surgical modalities. Medical treatment should be initiated early as it effectively arrests hair loss progression rather than stimulating regrowth. Minoxidil continues to be the first line therapy whereas anti-androgens form the second line of treatment. The progressive nature of FPHL mandates long-term treatment for sustained effect. Medical therapy may be supplemented with cosmetic concealment in those desirous of greater hair density. Surgery may be worthwhile in some carefully selected patients.

  4. HEARING LOSS IN DECOMPRESSION

    Science.gov (United States)

    hearing loss is often reported. Most of this can readily be attributed to the residual effects of repeated aerotitis media, and is not sudden. A review of the topic of sudden deafness reveals that every large hospital where such records have been published sees every month about 1-2 patients whose sudden deafness is not easily explained. Possible causes have been suggested: acute neuritis of the VIIIth nerve, virus infection, vascular accident, vasomotor neurosis, acoustic trauma at levels of noise not usually noxious, collagen disease, transient ischemia from violent

  5. Beam Loss Monitoring System for the LHC

    CERN Document Server

    Holzer, E B; Effinger, E; Emery, J; Ferioli, G; González, J L; Gschwendtner, E; Guaglio, G; Hodgson, M; Kramer, Daniel; Leitner, R; Ponce, L; Prieto, V; Stockner, M; Zamantzas, C

    2005-01-01

    One of the most critical elements for the protection of CERN's Large Hadron Collider (LHC) is its beam loss monitoring (BLM) system. It must prevent the superconducting magnets from quenching and protect the machine components from damages, as a result of critical beam losses. By measuring the loss pattern, the BLM system helps to identify the loss mechanism. Special monitors will be used for the setup and control of the collimators. The specification for the BLM system includes a very high reliability (tolerable failure rate of 10.-7 per hour) and a high dynamic range of 10.8 (10.13 at certain locations) of the particle fluencies to be measured. In addition, a wide range of integration times (40 micro/s to 84s) and a fast (one turn) trigger generation for the dump signal are required. This paper describes the complete design of the BLM system, including the monitor types (ionization chambers and secondary emission monitors), the design of the analogue and digital readout electronics as well as the data links...

  6. Tragic loss at CERN

    CERN Multimedia

    CERN Ski Club

    2015-01-01

    Tragic loss at CERN The CERN community is mourning the tragic loss of two members of the CERN Ski Club. On Sunday, April 12, an avalanche buried four out of five skiers, taking part in a ski touring in the region of the Becs de Bosson in Valais (CH). The fifth skier, who had not been buried in the snow,  courageously managed to save two of the skiers, but Hervé Milcent, 49 years, federal ski instructor, and Mattieu Cattin, 33 years, were buried under two to three meters of snow, far down the avalanche slope, and did not survive, despite the fast arrival of the mountain rescue. In its 40 years of existence, the CERN Ski Club, one of the biggest in the Geneva area, has never been confronted with such a tragedy. The passing of Hervé and Matthieu has deeply shocked and saddened all volunteers of the Club as well as the entire alpine community. The ski touring section of the club would like to honour its friend Hervé, who joined the club in 1998. In 2003 he became res...

  7. Loss, yearning and curiosity

    Directory of Open Access Journals (Sweden)

    Dariusz Sośnicki

    2011-01-01

    Full Text Available In his piece, the author of the article ponders on the experience of loss in human life. It is this particular experience, as well as the accompanying longing, that form the basic components of an elegiac attitude. However, in its broader sense, loss becomes one of the most universal experiences in literature and the arts of the twentieth century. After all, they shared the conviction that reality, no matter how looked upon, was never fully accessible to us and that man always played a losing game with it. Contrary to outward appearances, the above also applies to the creators of avant-garde movements. An analysis of the poem Do NN***, written by Miron Białoszewski, carried out first within the context of elegy and then with reference to the techniques and the program of cubism, makes us aware that Białoszewski somehow evades both elegiac mood and the avant-garde principles such as they are underlined in its program. The driving force for his writing is then curiosity. And it is curiosity, and just curiosity, independent and one that cannot be reduced to just the desire to know, that forms the only real alternative that, in a way, always remains metaphysical.

  8. Signaling pathways controlling skeletal muscle mass.

    Science.gov (United States)

    Egerman, Marc A; Glass, David J

    2014-01-01

    The molecular mechanisms underlying skeletal muscle maintenance involve interplay between multiple signaling pathways. Under normal physiological conditions, a network of interconnected signals serves to control and coordinate hypertrophic and atrophic messages, culminating in a delicate balance between muscle protein synthesis and proteolysis. Loss of skeletal muscle mass, termed "atrophy", is a diagnostic feature of cachexia seen in settings of cancer, heart disease, chronic obstructive pulmonary disease, kidney disease, and burns. Cachexia increases the likelihood of death from these already serious diseases. Recent studies have further defined the pathways leading to gain and loss of skeletal muscle as well as the signaling events that induce differentiation and post-injury regeneration, which are also essential for the maintenance of skeletal muscle mass. In this review, we summarize and discuss the relevant recent literature demonstrating these previously undiscovered mediators governing anabolism and catabolism of skeletal muscle.

  9. Digital signal processing laboratory

    CERN Document Server

    Kumar, B Preetham

    2011-01-01

    INTRODUCTION TO DIGITAL SIGNAL PROCESSING Brief Theory of DSP ConceptsProblem SolvingComputer Laboratory: Introduction to MATLAB®/SIMULINK®Hardware Laboratory: Working with Oscilloscopes, Spectrum Analyzers, Signal SourcesDigital Signal Processors (DSPs)ReferencesDISCRETE-TIME LTI SIGNALS AND SYSTEMS Brief Theory of Discrete-Time Signals and SystemsProblem SolvingComputer Laboratory: Simulation of Continuous Time and Discrete-Time Signals and Systems ReferencesTIME AND FREQUENCY ANALYSIS OF COMMUNICATION SIGNALS Brief Theory of Discrete-Time Fourier Transform (DTFT), Discrete Fourier Transform

  10. Global heterochromatin loss: a unifying theory of aging?

    Science.gov (United States)

    Tsurumi, Amy; Li, Willis X

    2012-07-01

    The aging field is replete with theories. Over the past years, many distinct, yet overlapping mechanisms have been proposed to explain organismal aging. These include free radicals, loss of heterochromatin, genetically programmed senescence, telomere shortening, genomic instability, nutritional intake and growth signaling, to name a few. The objective of this Point-of-View is to highlight recent progress on the "loss of heterochromatin" model of aging and to propose that epigenetic changes contributing to global heterochromatin loss may underlie the various cellular processes associated with aging.

  11. Breast Cancer and Bone Loss

    Science.gov (United States)

    ... Menopause Map Featured Resource Find an Endocrinologist Search Breast Cancer and Bone Loss July 2010 Download PDFs English ... G. Komen Foundation What is the link between breast cancer and bone loss? Certain treatments for breast cancer ...

  12. Loss of a spouse - resources

    Science.gov (United States)

    Resources - loss of a spouse ... The following organizations provide information on the loss of a spouse or significant other: GoodTherapy.org -- www.goodtherapy.org/learn-about-therapy/issues/grief National Institute on Aging -- www.nia.nih. ...

  13. Overweight, Obesity, and Weight Loss

    Science.gov (United States)

    ... Back to section menu Healthy Weight Weight and obesity Underweight Weight, fertility, and pregnancy Weight loss and ... section Home Healthy Weight Healthy Weight Weight and obesity Underweight Weight, fertility, and pregnancy Weight loss and ...

  14. Noise and Hearing Loss Prevention

    Science.gov (United States)

    ... visit this page: About CDC.gov . NOISE AND HEARING LOSS PREVENTION Recommend on Facebook Tweet Share Compartir Hearing ... noise levels cannot be adequately reduced. Noise and Hearing Loss on the NIOSH Science Blog Read and comment ...

  15. Hearing Loss and Older Adults

    Science.gov (United States)

    ... noise-induced hearing loss. Many construction workers, farmers, musicians, airport workers, yard and tree care workers, and ... Loss Do You Need a Hearing Test? News Brain training can improve our understanding of speech in ...

  16. Loss and terminal illness.

    Science.gov (United States)

    Benoliel, J Q

    1985-06-01

    The experience of terminal illness can best be viewed as a situation of multiple losses involving the dying person, family members and friends, and the health care providers engaged in offering services to them. It is a major transition during which the central participants must cope with the personal meanings of the forthcoming death as well as other losses brought about by the disease process, medical treatments, and the need to provide care for the dying person. How families adapt to the stresses and changes imposed by the experience of living with dying depends on their previous experiences with death, their established patterns of communication about serious matters, and their decision-making practices. Some individuals and families are at greater risk than others for developing maladaptive responses and behaviors during and after the experience of terminal illness. Risk factors to be considered in making hypotheses about the potential for maladaptive reactions include the strength of the attachment to the dying person, uncontrollable and distressing symptoms, and coping limitations associated with age and other factors contributing to increased vulnerability to the demands of continuous change. Working effectively with different kinds of families during the transition of terminal illness can best be accomplished within a conceptual framework built upon knowledge about people undergoing change. The concept of safe conduct can serve as an overall guide for the creation of nursing services designed to offer personalized care and accessibility of professional help at times of maximum need by the family. Assisting dying patients and their families toward the achievement of their personal goals is fundamental to the idea of safe conduct. The delivery of nursing care in terminal illness requires an orientation to assessment as an ongoing process that makes use of knowledge about disease processes, medical treatments, individual and group adaptations to loss, risk

  17. Weigth loss strategies

    Directory of Open Access Journals (Sweden)

    Magnus Benetti

    2004-06-01

    Full Text Available Although it does not represent a great isolated cause of death, obesity may be considered one of the greatest health problems nowadays because it is associated with several diseases. Inorder to avoid both increase and appearance of new cases of obesity, it is paramount that preventive measures should be taken. Prevention may be implemented through changes in lifestyle, such as eating habits re-education and the practice of physical exercises. The objective of this study was to review what type of physical exercise and also the strategies that may be adopted in exercise prescription of to optimize weight loss. It was observed that muscular resistance exercise combined with aerobic exercise seemed to produce the best results in weight loss programs because they help to increase resting metabolic rate, to keep and/or increase fat-free mass and optimize the rate of mobilization, and use of fat during weight loss. The weight loss goal seems to be successfully reached in programs that included resistance exercise, continuous and/or intermittent aerobic exercises which demand a high energy flow (70% VO2máx.. This process seemed to be more efficient because it afforded a greater total caloric expenditure; not only during exercise, but also because it triggered an increase in post-exercise oxygen consumption, thus causing fat to be used during this period. RESUMO A obesidade pode ser considerada um dos maiores problemas de saúde da atualidade por estar associada a inúmeras doenças, apesar de não representar uma grande causa isolada de morte. Para evitar tanto o crescimento como o surgimento de novos casos de obesidade, faz-se necessário que medidas de prevenção sejam tomadas. A prevenção é realizada através de mudanças no estilo de vida, como reeducação alimentar e inclusão da prática de exercícios físicos. O objetivo desta revisão foi abordar qual o tipo de exercício físico e também as estratégias que podem ser adotadas na

  18. Hypnotherapy in Weight Loss Treatment.

    Science.gov (United States)

    Cochrane, Gordon; Friesen, John

    1986-01-01

    Investigated effects of hypnosis as a treatment for weight loss among women. The primary hypothesis that hypnosis is an effective treatment for weight loss was confirmed, but seven concomitant variables and the use of audiotapes were not significant contributors to weight loss. (Author/ABB)

  19. Loss Aversion and Individual Characteristics

    DEFF Research Database (Denmark)

    Hjorth, Katrine; Fosgerau, Mogens

    2011-01-01

    Many studies have shown that loss aversion affects the valuation of non-market goods. Using stated choice data, this paper presents an empirical investigation of how individual-level loss aversion varies with observable personal characteristics and with the choice context. We investigate loss...

  20. Losses compensation; Compensation des pertes

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2001-07-01

    One mission of RTE (Electric Power Transportation), is to watch over the losses compensation resulting from the power transport on the electric power network. Since january 2001, RTE makes good the electric losses by the purchase of energy. To choose the marketers, a consultation has been realized by RTE. This document presents the rules concerning these losses compensation. (A.L.B.)

  1. Prediction of Path loss Estimate for a Frequency Modulation (FM ...

    African Journals Online (AJOL)

    This paper presents the path loss model that seeks to predict the signal strength degradation of Radio Nigeria, FM station, Makurdi which is normally a major component in the analysis and design of link budget of a telecommunication system. For the purpose of this work, Benue state was divided into four (4) routes for ease ...

  2. Sensorineural hearing loss in children.

    LENUS (Irish Health Repository)

    Wormald, R

    2010-02-01

    The objective of the study was to examine the aetiology of sensorineural hearing loss (SNHL) in a paediatric population presenting to the National Centre of Medical Genetics. A retrospective chart review from 1998 to 2006. One hundred and twenty nine children were investigated for SNHL. The average age of diagnosis of hearing loss was 36 months. The degree of hearing loss was mild in 8 children, moderate in 33 children, severe in 31 children and profound in 57 children. Eighty-five children (66%) were diagnosed with a hereditary hearing loss, 11 (8%) children had an acquired hearing loss and no cause found in 33 (26%) children. This is the first report of the causes of hearing loss in Irish children. The mean age of diagnosis in our cohort is high and emphasises the need for a neonatal screening programme. There remains a number of children for whom the cause of hearing loss remains unknown.

  3. Digital signal processing based on inverse scattering transform.

    Science.gov (United States)

    Turitsyna, Elena G; Turitsyn, Sergei K

    2013-10-15

    Through numerical modeling, we illustrate the possibility of a new approach to digital signal processing in coherent optical communications based on the application of the so-called inverse scattering transform. Considering without loss of generality a fiber link with normal dispersion and quadrature phase shift keying signal modulation, we demonstrate how an initial information pattern can be recovered (without direct backward propagation) through the calculation of nonlinear spectral data of the received optical signal.

  4. The MVAD pump: motor stator core loss characterization.

    Science.gov (United States)

    Mesa, Kelly J; Ferreira, Antonio; Castillo, Samir; Reyes, Carlos; Wolman, Justin; Casas, Fernando

    2015-01-01

    Investigation of the miniature ventricular assist device (MVAD) pump motor stator core loss behavior was conducted. During operation, the ferromagnetic core in the pump's motor is magnetized by alternating magnetic fields, which, in turn, create intrinsic energy losses in the core material; these losses are known as core losses. A core loss fixture and a method to characterize the magnetic behavior of the MVAD pump stator over a range of frequencies were developed. The MVAD pump motor design features a three phase brushless DC stator with ferromagnetic laminations and copper wire windings arranged in a six slot configuration. The stator's magnetic behavior is important because its core magnetic losses impact pump system efficiency. A system to measure the core loss of MVAD pump stators was developed using a custom core loss fixture consisting of 16 copper wire turns wound in a closed loop geometry bundle; the stator under test was then placed within this bundle. The instrumentation consisted of a signal generator, a power amplifier, and a power analyzer. Power analyzer parameters of current, voltage, and power were collected for several runs with a sinusoidal frequency sweep of 0 to 50 kHz; data were collected for the fixture with and without stators. The magnetic losses inherent to the fixture were characterized independently as a baseline presenting a flat frequency response. The core loss power measurements of individual stators yielded a characteristic bandpass frequency response morphology with a peak core loss found around 2.3 to 2.5 kHz. In conclusion, this method could be used to describe the transfer function of the stator's core magnetic behavior. It also has the potential to be used for future motor evaluation and for investigation of core loss performance variability between different stators during manufacturing operations. Investigational device. Limited by United States law to investigational use.

  5. Dynamics in atomic signaling games

    KAUST Repository

    Fox, Michael J.

    2015-04-08

    We study an atomic signaling game under stochastic evolutionary dynamics. There are a finite number of players who repeatedly update from a finite number of available languages/signaling strategies. Players imitate the most fit agents with high probability or mutate with low probability. We analyze the long-run distribution of states and show that, for sufficiently small mutation probability, its support is limited to efficient communication systems. We find that this behavior is insensitive to the particular choice of evolutionary dynamic, a property that is due to the game having a potential structure with a potential function corresponding to average fitness. Consequently, the model supports conclusions similar to those found in the literature on language competition. That is, we show that efficient languages eventually predominate the society while reproducing the empirical phenomenon of linguistic drift. The emergence of efficiency in the atomic case can be contrasted with results for non-atomic signaling games that establish the non-negligible possibility of convergence, under replicator dynamics, to states of unbounded efficiency loss.

  6. Dynamics in atomic signaling games.

    Science.gov (United States)

    Fox, Michael J; Touri, Behrouz; Shamma, Jeff S

    2015-07-07

    We study an atomic signaling game under stochastic evolutionary dynamics. There are a finite number of players who repeatedly update from a finite number of available languages/signaling strategies. Players imitate the most fit agents with high probability or mutate with low probability. We analyze the long-run distribution of states and show that, for sufficiently small mutation probability, its support is limited to efficient communication systems. We find that this behavior is insensitive to the particular choice of evolutionary dynamic, a property that is due to the game having a potential structure with a potential function corresponding to average fitness. Consequently, the model supports conclusions similar to those found in the literature on language competition. That is, we show that efficient languages eventually predominate the society while reproducing the empirical phenomenon of linguistic drift. The emergence of efficiency in the atomic case can be contrasted with results for non-atomic signaling games that establish the non-negligible possibility of convergence, under replicator dynamics, to states of unbounded efficiency loss. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Platelet signaling-a primer.

    Science.gov (United States)

    Goggs, Robert; Poole, Alastair W

    2012-02-01

    To review the receptors and signal transduction pathways involved in platelet plug formation and to highlight links between platelets, leukocytes, endothelium, and the coagulation system. Original studies, review articles, and book chapters in the human and veterinary medical fields. Platelets express numerous surface receptors. Critical among these are glycoprotein VI, the glycoprotein Ib-IX-V complex, integrin α(IIb) β(3) , and the G-protein-coupled receptors for thrombin, ADP, and thromboxane. Activation of these receptors leads to various important functional events, in particular activation of the principal adhesion receptor α(IIb) β(3) . Integrin activation allows binding of ligands such as fibrinogen, mediating platelet-platelet interaction in the process of aggregation. Signals activated by these receptors also couple to 3 other important functional events, secretion of granule contents, change in cell shape through cytoskeletal rearrangement, and procoagulant membrane expression. These processes generate a stable thrombus to limit blood loss and promote restoration of endothelial integrity. Improvements in our understanding of how platelets operate through their signaling networks are critical for diagnosis of unusual primary hemostatic disorders and for rational antithrombotic drug design. © Veterinary Emergency and Critical Care Society 2012.

  8. Signal sciences workshop proceedings

    Energy Technology Data Exchange (ETDEWEB)

    Candy, J.V.

    1997-05-01

    This meeting is aimed primarily at signal processing and controls. The technical program for the 1997 Workshop includes a variety of efforts in the Signal Sciences with applications in the Microtechnology Area a new program at LLNL and a future area of application for both Signal/Image Sciences. Special sessions organized by various individuals in Seismic and Optical Signal Processing as well as Micro-Impulse Radar Processing highlight the program, while the speakers at the Signal Processing Applications session discuss various applications of signal processing/control to real world problems. For the more theoretical, a session on Signal Processing Algorithms was organized as well as for the more pragmatic, featuring a session on Real-Time Signal Processing.

  9. Retinoid signalling during embryogenesis

    NARCIS (Netherlands)

    Pijnappel, W.W.M.; Hendriks, H.F.J.; Durston, A.J.

    1996-01-01

    Conclusion: Retinoids are suspected to have multiple functions during embryogenesis, which are carried out via various different signal transduction pathways involving active retinoids and nuclear retinoid receptors. Research focuses on the identification of the retinoid signal transduction

  10. Biomedical signal processing

    CERN Document Server

    Akay, Metin

    1994-01-01

    Sophisticated techniques for signal processing are now available to the biomedical specialist! Written in an easy-to-read, straightforward style, Biomedical Signal Processing presents techniques to eliminate background noise, enhance signal detection, and analyze computer data, making results easy to comprehend and apply. In addition to examining techniques for electrical signal analysis, filtering, and transforms, the author supplies an extensive appendix with several computer programs that demonstrate techniques presented in the text.

  11. Tetrapyrrole Signaling in Plants

    Directory of Open Access Journals (Sweden)

    Robert M. Larkin

    2016-10-01

    Full Text Available Tetrapyrroles make critical contributions to a number of important processes in diverse organisms. In plants, tetrapyrroles are essential for light signaling, the detoxification of reactive oxygen species, the assimilation of nitrate and sulfate, respiration, photosynthesis, and programed cell death. Thus, it is not surprising that tetrapyrrole metabolism is strictly regulated and that tetrapyrrole metabolism affects signaling mechanisms that regulate gene expression. In plants and algae, tetrapyrroles are synthesized in plastids and were some of the first plastid signals demonstrated to regulate nuclear gene expression. In plants, the mechanism of tetrapyrrole-dependent plastid-to-nucleus signaling remains poorly understood. Additionally, some of experiments that tested ideas for possible signaling mechanisms appeared to produce conflicting data. In some instances, these conflicts are potentially explained by different experimental conditions. Although the biological function of tetrapyrrole signaling is poorly understood, there is compelling evidence that this signaling is significant. Specifically, this signaling appears to affect the accumulation of starch and may promote abiotic stress tolerance. Tetrapyrrole-dependent plastid-to-nucleus signaling interacts with a distinct plastid-to-nucleus signaling mechanism that depends on GENOMES UNCUOPLED1 (GUN1. GUN1 contributes to a variety of processes, such as chloroplast biogenesis, the circadian rhythm, abiotic stress tolerance, and development. Thus, the contribution of tetrapyrrole signaling to plant function is potentially broader than we currently appreciate. In this review, I discuss these aspects of tetrapyrrole signaling.

  12. Growth factor signalling

    NARCIS (Netherlands)

    De Laat, SW; Boonstra, J; Defize, LHK; Kruijer, W; Van der Saag, PT; Tertoolen, LGJ; Van Zoelen, JJ; Den Hertog, J

    1999-01-01

    Signalling between cells in the developing vertebrate embryo is essential for nomal embryonic development. In the mid 1970's, signal transduction research started at the Hubrecht Laboratory with special emphasis on analysis of the signalling mechanisms that direct cell proliferation and

  13. Unilateral Vestibular Loss Impairs External Space Representation

    Science.gov (United States)

    Borel, Liliane; Redon-Zouiteni, Christine; Cauvin, Pierre; Dumitrescu, Michel; Devèze, Arnaud; Magnan, Jacques; Péruch, Patrick

    2014-01-01

    The vestibular system is responsible for a wide range of postural and oculomotor functions and maintains an internal, updated representation of the position and movement of the head in space. In this study, we assessed whether unilateral vestibular loss affects external space representation. Patients with Menière's disease and healthy participants were instructed to point to memorized targets in near (peripersonal) and far (extrapersonal) spaces in the absence or presence of a visual background. These individuals were also required to estimate their body pointing direction. Menière's disease patients were tested before unilateral vestibular neurotomy and during the recovery period (one week and one month after the operation), and healthy participants were tested at similar times. Unilateral vestibular loss impaired the representation of both the external space and the body pointing direction: in the dark, the configuration of perceived targets was shifted toward the lesioned side and compressed toward the contralesioned hemifield, with higher pointing error in the near space. Performance varied according to the time elapsed after neurotomy: deficits were stronger during the early stages, while gradual compensation occurred subsequently. These findings provide the first demonstration of the critical role of vestibular signals in the representation of external space and of body pointing direction in the early stages after unilateral vestibular loss. PMID:24523916

  14. Unilateral vestibular loss impairs external space representation.

    Directory of Open Access Journals (Sweden)

    Liliane Borel

    Full Text Available The vestibular system is responsible for a wide range of postural and oculomotor functions and maintains an internal, updated representation of the position and movement of the head in space. In this study, we assessed whether unilateral vestibular loss affects external space representation. Patients with Menière's disease and healthy participants were instructed to point to memorized targets in near (peripersonal and far (extrapersonal spaces in the absence or presence of a visual background. These individuals were also required to estimate their body pointing direction. Menière's disease patients were tested before unilateral vestibular neurotomy and during the recovery period (one week and one month after the operation, and healthy participants were tested at similar times. Unilateral vestibular loss impaired the representation of both the external space and the body pointing direction: in the dark, the configuration of perceived targets was shifted toward the lesioned side and compressed toward the contralesioned hemifield, with higher pointing error in the near space. Performance varied according to the time elapsed after neurotomy: deficits were stronger during the early stages, while gradual compensation occurred subsequently. These findings provide the first demonstration of the critical role of vestibular signals in the representation of external space and of body pointing direction in the early stages after unilateral vestibular loss.

  15. SLIT/ROBO2 Signaling Promotes Mammary Stem Cell Senescence by Inhibiting Wnt Signaling

    Directory of Open Access Journals (Sweden)

    Gwyndolen Harburg

    2014-09-01

    Full Text Available WNT signaling stimulates the self-renewal of many types of adult stem cells, including mammary stem cells (MaSCs, but mechanisms that limit this activity are poorly understood. Here, we demonstrate that SLIT2 restricts stem cell renewal by signaling through ROBO2 in a subset of basal cells to negatively regulate WNT signaling. The absence of SLIT/ROBO2 signaling leads to increased levels of nuclear β-catenin. Robo2 loss does not increase the number of stem cells; instead, stem cell renewal is enhanced in the absence of SLIT/ROBO2 signaling. This is due to repressed expression of p16 INK4a, which, in turn, delays MaSC senescence. Together, our studies support a model in which SLITs restrict the expansion of MaSCs by countering the activity of WNTs and limiting self-renewal.

  16. Analysis of detectability loss through fan-beam x-ray computed tomography reconstruction

    Science.gov (United States)

    Sanchez, Adrian A.; Sidky, Emil Y.; Pan, Xiaochuan

    2013-03-01

    We consider detection of a small signal in fan-beam x-ray computed tomography (CT). In order to characterize the loss of intrinsic signal detectability from the projection data (sinogram) domain to the reconstructed image, we analyze the Hotelling observer SNR in each domain. Further, we characterize the loss of Hotelling observer SNR through decomposition into two components: loss of signal detectability which arises due to unequal variance in the noise of separate detector elements and loss of detectability arising from the fact that some noiseless signals have components which lie in the nullspace of a given reconstruction operator. The proposed methodology is investigated for the back-projection ltration (BPF) algorithm developed by our group [2].

  17. The Signal Distribution System

    CERN Document Server

    Belohrad, D; CERN. Geneva. AB Department

    2005-01-01

    For the purpose of LHC signal observation and high frequency signal distribution, the Signal Distribution System (SDS) was built. The SDS can contain up to 5 switching elements, where each element allows the user to switch between one of the maximum 8 bi-directional signals. The coaxial relays are used to switch the signals. Depending of the coaxial relay type used, the transfer bandwidth can go up to 18GHz. The SDS is controllable via TCP/IP, parallel port, or locally by rotary switch.

  18. Occupational Hearing Loss in Korea

    OpenAIRE

    Kim, Kyoo Sang

    2010-01-01

    In this article, current status of noise exposure in workplaces, trend of workers with noise-induced hearing loss (NIHL), and prevalence of NIHL in workers by industry and job category in Korea were reviewed. In addition, trends of research on the audiological effects such as hearing loss from noise and occupational hearing loss from non-noise in Korea were addressed through reports in industrial audiology. Though noise exposure level has improved, noise still shows the highest rate of cases ...

  19. Estimated Blood Loss in Craniotomy

    OpenAIRE

    Sitohang, Diana; AM, Rachmawati; Arif, Mansyur

    2016-01-01

    Introduction: Estimated blood loss is an estimation of how much blood is loss during surgery. Surgical procedure requires a preparation of blood stock, but the demand for blood often larger than the actual blood used. This predicament happens because there is no blood requirement protocol being used. This study aims to determine the estimated blood loss during craniotomy procedure and it's conformity to blood units ordered for craniotomy procedure. Methods: This study is a retrospective study...

  20. Drug-induced hair loss.

    Science.gov (United States)

    2016-05-01

    Hair loss can have major psychological consequences. It can be due to a wide variety of causes, including hormonal disorders, dietary factors, infections, inflammation, trauma, emotional factors, and cancer. Drugs can also induce hair loss, by interacting with the hair growth cycle. Drug-induced hair loss may be immediate or delayed, sudden or gradual, and diffuse or localised. It is usually reversible after drug discontinuation. The drugs most often implicated in hair loss are anticancer agents, interferon, azole antifungals, lithium, immunosuppressants, and many other drugs belonging to a variety of pharmacological classes.

  1. Systemic causes of hair loss.

    Science.gov (United States)

    Lin, Richard L; Garibyan, Lilit; Kimball, Alexandra B; Drake, Lynn A

    2016-09-01

    Hair loss is both a common chief complaint by patients and a clinical challenge for physicians, especially general practitioners, yet few dermatological problems yield as much patient satisfaction when resolved as hair loss. The diagnosis is often attributed to androgen-related hair loss, while other causes, some of which are life-threatening but treatable, are overlooked. We searched for relevant literature on hair loss and supported these findings with our clinical experience to identify seven major systemic etiologies of hair loss, ranging from infectious agents to consumption of unsafe supplements. Many causes are only described in the literature through case studies, though some original articles and meta-analyses are available. Careful history taking, proper examination techniques, and judicious use of laboratory tests are essential to reach at the correct diagnosis in a cost-effective manner when performing patient work-up. Such methodical evaluation of hair loss can result in the appropriate treatment plan and provide significant patient satisfaction. Key messages Hair loss is a common chief complaint and a difficult challenge for both general practitioners and dermatology consultants. We identified seven major categories of systemic hair loss etiology and present a framework for their clinical evaluation. A methodical approach to hair loss can result in the appropriate treatment plan and provide significant patient satisfaction.

  2. Hydraulic Losses in River Meanders

    National Research Council Canada - National Science Library

    Brown, Gary L; Copeland, Ronald R; Fischenich, Craig

    2007-01-01

    Energy losses along a channel reach occur from friction along the channel boundaries and bed surface and channel irregularities, obstructions, vegetation, channel meandering, and many other parameters...

  3. Feather loss in laying hens

    OpenAIRE

    Hristov Slavča; Mitrović Sreten; Todorović Mirjana; Đermanović Vladan; Cvetković Ivica

    2006-01-01

    The paper examined the incidence of different forms of feather loss and cannibalism in laying hens aged 74 weeks following moulting and in laying hens following exploitation for a period of one year. The forms of feather loss were considered in detail through a repeated examination of video recordings and they were sorted according to localization - to feather loss on the ventral part of the neck, on the dorsal part of the neck, and on the back between the wings. Feather loss on the ventral p...

  4. Estimation of Threshold for the Signals of the BLMs around the LHC Final Focus Triplet Magnets

    CERN Document Server

    Cerutti, F; Ferrari, A; Hoa, C; Mauri, M; Mereghetti, A; Sapinski, M; Wildner, E; CERN. Geneva. ATS Department

    2012-01-01

    The Interaction Points of the Large Hadron Collider are the regions where the two circulating beams collide. Hence, the magnets the closest to any Interaction Point are exposed to an elevated radiation field due to the collision debris. In this study the signal in the Beam Loss Monitors due to the debris is estimated. In addition, for three different scenarios of beam losses, the energy density in the coils and the signal in the Beam Loss Monitors at quench are computed. It is shown that the Beam Loss Monitors, as presently installed on the vacuum vessel of the magnets, cannot disentangle the signal due to a localised loss from the constant signal due to the debris in case of steady-state losses.

  5. Estimation of thresholds for the signals of the BLMs around the LHC final focus triplet magnets

    CERN Document Server

    Sapinski, M; Dehning, B; Ferrari, A; Hoa, C; Lechner, A; Mauri, M; Mereghetti, A

    2012-01-01

    The Interaction Points of the Large Hadron Collider are the regions where the two circulating beams collide. Hence, the magnets closest to any Interaction Point are exposed to an elevated radiation field due to the collision debris. In this study the signal in the Beam Loss Monitors due to the debris is estimated and compared with the measurements. In addition, the energy density in the coils and the signal in the Beam Loss Monitors at quench are estimated for a beam loss scenario. It is shown that the Beam Loss Monitors, as presently installed on the vacuum vessel of the magnets, cannot disentangle the signal due to a localized loss from the constant signal due to the debris in case of steady-state losses.

  6. Computation of loss allocation in electric power networks using loss ...

    African Journals Online (AJOL)

    This paper presents the computation of loss allocation that can be applied to sellers and buyers participating in electric power trade in a deregulated power market. The approach is based on the Jacobian and Hessian matrices of the power flow equations. The losses to be allocated are derived from load flow of a specified ...

  7. Low Loss and Highly Birefringent Hollow-Core Photonic Crystal Fiber

    DEFF Research Database (Denmark)

    Roberts, P. John; Williams, D.P.; Mangan, Brian J.

    2006-01-01

    A hollow-core photonic crystal fiber design is proposed which enables both low-loss and polarization-maintained signal propagation. The design relies on an arrangement of antiresonant features positioned on the glass ring that surrounds the air core.......A hollow-core photonic crystal fiber design is proposed which enables both low-loss and polarization-maintained signal propagation. The design relies on an arrangement of antiresonant features positioned on the glass ring that surrounds the air core....

  8. Beam Loss Patterns at the LHC Collimators Measurements & Simulations

    CERN Document Server

    Böhlen, Till Tobias

    2008-01-01

    The Beam Loss Monitoring (BLM) system of the Large Hadron Collider (LHC) detects particle losses of circulating beams and initiates an emergency extraction of the beam in case that the BLM thresholds are exceeded. This protection is required as energy deposition in the accelerator equipment due to secondary shower particles can reach critical levels; causing damage to the beam-line components and quenches of superconducting magnets. Robust and movable beam line elements, so-called collimators, are the aperture limitations of the LHC. Consequently, they are exposed to the excess of lost beam particles and their showers. Proton loss patterns at LHC collimators have to be determined to interpret the signal of the BLM detectors and to set adequate BLM thresholds for the protection of collimators and other equipment in case of unacceptably increased loss rates. The first part of this work investigates the agreement of BLM detector measurements with simulations for an LHC-like collimation setup. The setup consists ...

  9. The Hedgehog Signal Induced Modulation of Bone Morphogenetic Protein Signaling: An Essential Signaling Relay for Urinary Tract Morphogenesis

    Science.gov (United States)

    Nakagata, Naomi; Miyagawa, Shinichi; Suzuki, Kentaro; Kitazawa, Sohei; Yamada, Gen

    2012-01-01

    Background Congenital diseases of the urinary tract are frequently observed in infants. Such diseases present a number of developmental anomalies such as hydroureter and hydronephrosis. Although some genetically-modified mouse models of growth factor signaling genes reproduce urinary phenotypes, the pathogenic mechanisms remain obscure. Previous studies suggest that a portion of the cells in the external genitalia and bladder are derived from peri-cloacal mesenchymal cells that receive Hedgehog (Hh) signaling in the early developmental stages. We hypothesized that defects in such progenitor cells, which give rise to urinary tract tissues, may be a cause of such diseases. Methodology/Principal Findings To elucidate the pathogenic mechanisms of upper urinary tract malformations, we analyzed a series of Sonic hedgehog (Shh) deficient mice. Shh−/− displayed hydroureter and hydronephrosis phenotypes and reduced expression of several developmental markers. In addition, we suggested that Shh modulation at an early embryonic stage is responsible for such phenotypes by analyzing the Shh conditional mutants. Tissue contribution assays of Hh-responsive cells revealed that peri-cloacal mesenchymal cells, which received Hh signal secreted from cloacal epithelium, could contribute to the ureteral mesenchyme. Gain- and loss-of-functional mutants for Hh signaling revealed a correlation between Hh signaling and Bone morphogenetic protein (Bmp) signaling. Finally, a conditional ablation of Bmp receptor type IA (BmprIA) gene was examined in Hh-responsive cell lineages. This system thus made it possible to analyze the primary functions of the growth factor signaling relay. The defective Hh-to-Bmp signaling relay resulted in severe urinary tract phenotypes with a decrease in the number of Hh-responsive cells. Conclusions/Significance This study identified the essential embryonic stages for the pathogenesis of urinary tract phenotypes. These results suggested that Hh

  10. The Stigma of Hearing Loss

    Science.gov (United States)

    Wallhagen, Margaret I.

    2010-01-01

    Purpose: To explore dimensions of stigma experienced by older adults with hearing loss and those with whom they frequently communicate to target interventions promoting engagement and positive aging. Design and Methods: This longitudinal qualitative study conducted interviews over 1 year with dyads where one partner had hearing loss. Participants…

  11. Partitioning recent Greenland mass loss

    NARCIS (Netherlands)

    van den Broeke, M.R.|info:eu-repo/dai/nl/073765643; Bamber, Jonathan L.; Ettema, J.|info:eu-repo/dai/nl/304831913; Rignot, Eric; Schrama, Ernst; van de Berg, W.J.|info:eu-repo/dai/nl/304831611; Velicogna, I.; Wouters, Bert|info:eu-repo/dai/nl/304120146

    2009-01-01

    Mass budget calculations, validated with satellite gravity observations [from the Gravity Recovery and Climate Experiment (GRACE) satellites], enable us to quantify the individual components of recent Greenland mass loss. The total 2000–2008 mass loss of ~1500 gigatons, equivalent to 0.46

  12. Pregnancy Loss: How to Cope

    Science.gov (United States)

    ... Lancet. 2015;385:222. Robinson GA. Pregnancy loss. Best Practice & Research: Clinical Obstetrics & Gynaecology, 2014;28:169. Chaisson J. ... between loss of control and searching for control. Research in Nursing & Health. 2014;37:267. Rink BD, et al. ...

  13. Bone loss, contraception and lactation.

    Science.gov (United States)

    Mehta, S

    1993-04-01

    Loss of bone mass with age, is a universal phenomenon and is more pronounced in women than in men. The condition where the bone loss has proceeded to the extent that fractures occur is termed osteoporosis. As the number of elderly persons in the population increases, its magnitude is likely to increase, both in the developing and the developed countries. Bone mass increases rapidly in childhood and the adolescent years, reaching a peak in the third decade of life, and begins to decline soon thereafter. Several factors are thought to influence bone loss: these include race, diet, smoking, and physical exercise. Although the rate of bone loss accelerates in the immediate postmenopausal period, the process actually begins in the premenopausal years. By the time osteoporosis is clinically apparent and manifested by fracture, it probably cannot be reversed. The peak adult bone mass achieved, and the subsequent rate of bone loss are the major factors that determine a woman's susceptibility to postmenopausal osteoporosis. A primary cause of bone loss after menopause is the associated decline in ovarian function. Scanty information is available on the factors that affect bone mineral density or initiate bone loss before menopause, although both estrogens and progestins have been shown to prevent bone loss in postmenopausal women. Available data on the relationship between steroid hormone contraceptive use and bone mass/density is limited to combined oral contraceptives and one report related to the use of depot medroxyprogesterone acetate.(ABSTRACT TRUNCATED AT 250 WORDS)

  14. Pregnancy Loss: How to Cope

    Science.gov (United States)

    ... 16:100. Ockhuijsen HDL, et al. Pregnancy after miscarriage: Balancing between loss of control and searching for control. Research in Nursing & Health. 2014;37:267. Rink BD, et al. Recurrent pregnancy loss. In: Creasy and Resnik's Maternal-Fetal ...

  15. NF1 Signal Transduction and Vascular Dysfunction

    Science.gov (United States)

    2014-05-01

    the effects of losing a second allele of NF1 in the vascular endothelium of the adult mouse. This will be the first model of NF1 loss in the... adult endothelium and can serve as a model system for investigation of both cardiovascular effects and the tumor microenvironment. Body: Aim 1...would be to try and determine if there were defects in TGF-b signaling (Smad activation/EndMT) prior to doing a wholesale catalog of all the

  16. Hearing Loss in Children: Data and Statistics

    Science.gov (United States)

    ... Hearing Loss Homepage Facts Noise-Induced Hearing Loss Genetics of Hearing Loss Screening & Diagnosis Types of Hearing Loss About Sound Treatment & Intervention Services Learning Language Bacterial Meningitis Studies Data & Statistics EHDI Annual Data 2015 ...

  17. Hearing Loss in Children: Screening and Diagnosis

    Science.gov (United States)

    ... Hearing Loss Homepage Facts Noise-Induced Hearing Loss Genetics of Hearing Loss Screening & Diagnosis Types of Hearing Loss About Sound Treatment & Intervention Services Learning Language Bacterial Meningitis Studies Data & Statistics EHDI Annual Data 2015 ...

  18. Ac loss measurements on a superconducting transformer for a 25 kA superconducting rectifier

    NARCIS (Netherlands)

    ten Kate, Herman H.J.; Mulders, J.M.; de Reuver, J.L.; van de Klundert, L.J.M.

    1984-01-01

    Ac loss measurements have been performed on a superconducting transformer. The transformer is a part of a 25 kA thermally switched superconducting rectifier operating at a frequency of 0.1 Hz. The loss measurements have been automatized by means of a microcomputer sampling four relevant signals and

  19. Correlation of in vivo neuroimaging abnormalities with postmortem human immunodeficiency virus encephalitis and dendritic loss

    DEFF Research Database (Denmark)

    Archibald, Sarah L.; Masliah, Eliezer; Fennema-Notestine, Christine

    2004-01-01

    BACKGROUND: In the absence of significant opportunistic infection, the most common alterations on neuroimaging in the brains of patients with AIDS include enlarged cerebrospinal fluid spaces, white-matter loss, volume loss in striatal structures, and white-matter signal abnormalities. Although pr...

  20. Superluminal Signal Velocity

    OpenAIRE

    Nimtz, Guenter

    1998-01-01

    It recently has been demonstrated that signals conveyed by evanescent modes can travel faster than light. In this report some special features of signals are introduced and investigated, for instance the fundamental property that signals are frequency band limited. Evanescent modes are characterized by extraordinary properties: Their energy is {\\it negative}, they are not directly measurable, and the evanescent region is not causal since the modes traverse this region instantaneously. The stu...

  1. Noncausal Superluminal Nonlocal Signalling

    OpenAIRE

    Srikanth, R.

    1999-01-01

    We propose a thought experiment for classical superluminal signal transmission based on the quantum nonlocal influence of photons on their momentum entangled EPR twins. The signal sender measures either position or momentum of particles in a pure ensemble of the entangled pairs, leaving their twins as localized particles or plane waves. The signal receiver distinguishes these outcomes interferometrically using a double slit interferometer modified by a system of optical filters. Since the col...

  2. Trends in global earthquake loss

    Science.gov (United States)

    Arnst, Isabel; Wenzel, Friedemann; Daniell, James

    2016-04-01

    Based on the CATDAT damage and loss database we analyse global trends of earthquake losses (in current values) and fatalities for the period between 1900 and 2015 from a statistical perspective. For this time period the data are complete for magnitudes above 6. First, we study the basic statistics of losses and find that losses below 10 bl. US satisfy approximately a power law with an exponent of 1.7 for the cumulative distribution. Higher loss values are modelled with the General Pareto Distribution (GPD). The 'transition' between power law and GPD is determined with the Mean Excess Function. We split the data set into a period of pre 1955 and post 1955 loss data as in those periods the exposure is significantly different due to population growth. The Annual Average Loss (AAL) for direct damage for events below 10 bl. US differs by a factor of 6, whereas the incorporation of the extreme loss events increases the AAL from 25 bl. US/yr to 30 bl. US/yr. Annual Average Deaths (AAD) show little (30%) difference for events below 6.000 fatalities and AAD values of 19.000 and 26.000 deaths per year if extreme values are incorporated. With data on the global Gross Domestic Product (GDP) that reflects the annual expenditures (consumption, investment, government spending) and on capital stock we relate losses to the economic capacity of societies and find that GDP (in real terms) grows much faster than losses so that the latter one play a decreasing role given the growing prosperity of mankind. This reasoning does not necessarily apply on a regional scale. Main conclusions of the analysis are that (a) a correct projection of historic loss values to nowadays US values is critical; (b) extreme value analysis is mandatory; (c) growing exposure is reflected in the AAL and AAD results for the periods pre and post 1955 events; (d) scaling loss values with global GDP data indicates that the relative size - from a global perspective - of losses decreases rapidly over time.

  3. Cavin-3 dictates the balance between ERK and Akt signaling

    Science.gov (United States)

    Hernandez, Victor J; Weng, Jian; Ly, Peter; Pompey, Shanica; Dong, Hongyun; Mishra, Lopa; Schwarz, Margaret; Michaely, Peter

    2013-01-01

    Cavin-3 is a tumor suppressor protein of unknown function. Using both in vivo and in vitro approaches, we show that cavin-3 dictates the balance between ERK and Akt signaling. Loss of cavin-3 increases Akt signaling at the expense of ERK, while gain of cavin-3 increases ERK signaling at the expense Akt. Cavin-3 facilitates signal transduction to ERK by anchoring caveolae to the membrane skeleton of the plasma membrane via myosin-1c. Caveolae are lipid raft specializations that contain an ERK activation module and loss of the cavin-3 linkage reduces the abundance of caveolae, thereby separating this ERK activation module from signaling receptors. Loss of cavin-3 promotes Akt signaling through suppression of EGR1 and PTEN. The in vitro consequences of the loss of cavin-3 include induction of Warburg metabolism (aerobic glycolysis), accelerated cell proliferation, and resistance to apoptosis. The in vivo consequences of cavin-3 knockout are increased lactate production and cachexia. DOI: http://dx.doi.org/10.7554/eLife.00905.001 PMID:24069528

  4. Digital signal processing

    CERN Document Server

    O'Shea, Peter; Hussain, Zahir M

    2011-01-01

    In three parts, this book contributes to the advancement of engineering education and that serves as a general reference on digital signal processing. Part I presents the basics of analog and digital signals and systems in the time and frequency domain. It covers the core topics: convolution, transforms, filters, and random signal analysis. It also treats important applications including signal detection in noise, radar range estimation for airborne targets, binary communication systems, channel estimation, banking and financial applications, and audio effects production. Part II considers sel

  5. Biomedical signals and systems

    CERN Document Server

    Tranquillo, Joseph V

    2013-01-01

    Biomedical Signals and Systems is meant to accompany a one-semester undergraduate signals and systems course. It may also serve as a quick-start for graduate students or faculty interested in how signals and systems techniques can be applied to living systems. The biological nature of the examples allows for systems thinking to be applied to electrical, mechanical, fluid, chemical, thermal and even optical systems. Each chapter focuses on a topic from classic signals and systems theory: System block diagrams, mathematical models, transforms, stability, feedback, system response, control, time

  6. Pediatric Sudden Sensorineural Hearing Loss.

    Science.gov (United States)

    Kizilay, Ahmet; Koca, Çiğdem Firat

    2016-06-01

    Sudden sensorineural hearing loss is defined as sudden unilateral or bilateral sensorineural hearing loss with at least 30 dB decrease in threshold in 3 contiguous test frequencies occurring over 72 hours or less. It is rare among children. The mechanism of the process and prognosis of the disorder remains unclear. The current incidence of sudden sensorineural hearing loss among pediatric population is unknown. The authors carried out a retrospective chart analysis of patients under 15 years of age from 2004 to 2015, who consulted to the Otolaryngology Head and Neck Surgery Department of Inonu University Medical Faculty. Age, sex, number of affected ear and side, audiometric evaluations, medical follow-up, treatment method, duration of treatment recovery, associated complaints; tinnitus and/or vertigo, presence of mumps disease were recorded for each patient. A 4-frequency pure-tone average (500, 1000, 2000, and 4000 Hz) was calculated for each ear. Complete recovery, defined as some hearing level compared with the nonaffected ear, was observed in 3 patients (21.4 %) and there was no partial hearing recovery. The hearing loss of 11 patient remained unchanged after prednisolone treatment. Two of the 11 patients had bilaterally total sensorineural hearing loss and evaluated as appropriate for cochlear implantation. Sex of patient and laterality of hearing loss were not correlated with hearing recovery. Sensorineural hearing loss among pediatrics has been the issue of otolaryngologists. The incidence, etiology, and treatment methods should be more studied.

  7. Effectiveness of Wavelet Denoising on Electroencephalogram Signals

    Directory of Open Access Journals (Sweden)

    Md. Mamun

    2013-02-01

    Full Text Available Analyzing Electroencephalogram (EEG signal is a challenge due to the various artifacts used by Electromyogram, eye blink and Electrooculogram. The present de-noising techniques that are based on the frequency selective filtering suffers from a substantial loss of the EEG data. Noise removal using wavelet has the characteristic of preserving signal uniqueness even if noise is going to be minimized. To remove noise from EEG signal, this research employed discrete wavelet transform. Root mean square difference has been used to find the usefulness of the noise elimination. In this research, four different discrete wavelet functions have been used to remove noise from the Electroencephalogram signal gotten from two different types of patients (healthy and epileptic to show the effectiveness of DWT on EEG noise removal. The result shows that the WF orthogonal meyer is the best one for noise elimination from the EEG signal of epileptic subjects and the WF Daubechies 8 (db8 is the best one for noise elimination from the EEG signal on healthy subjects.

  8. MAPK cascades in guard cell signal transduction

    Directory of Open Access Journals (Sweden)

    Yuree eLee

    2016-02-01

    Full Text Available Guard cells form stomata on the epidermis and continuously respond to endogenous and environmental stimuli to fine-tune the gas exchange and transpirational water loss, processes which involve mitogen-activated protein kinase (MAPK cascades. MAPKs form three-tiered kinase cascades with MAPK kinases and MAPK kinase kinases, by which signals are transduced to the target proteins. MAPK cascade genes are highly conserved in all eukaryotes, and they play crucial roles in myriad developmental and physiological processes. MAPK cascades function during biotic and abiotic stress responses by linking extracellular signals received by receptors to cytosolic events and gene expression. In this review, we highlight recent findings and insights into MAPK-mediated guard cell signaling, including the specificity of MAPK cascades and the remaining questions.

  9. Amygdala signals subjective appetitiveness and aversiveness of mixed gambles

    DEFF Research Database (Denmark)

    Gelskov, Sofie V.; Henningsson, Susanne; Madsen, Kristoffer Hougaard

    2015-01-01

    People are more sensitive to losses than to equivalent gains when making financial decisions. We used functional magnetic resonance imaging (fMRI) to illuminate how the amygdala contributes to loss aversion. The blood oxygen level dependent (BOLD) response of the amygdala was mapped while healthy...... and rejected gambles with equal probability. Amygdala activity increased the more the gain-loss ratio deviated from the individual decision boundary showing that the amygdala codes action value. This response pattern was more strongly expressed in loss aversive individuals, linking amygdala activity...... with individual differences in loss aversion. Together, the results show that the amygdala signals subjective appetitiveness or aversiveness of gain-loss ratios at the time of choice. (C) 2015 Elsevier Ltd. All rights reserved....

  10. Tunable negligible-loss energy transfer between dipolar-coupled magnetic disks by stimulated vortex gyration

    OpenAIRE

    Hyunsung Jung; Ki-Suk Lee; Dae-Eun Jeong; Youn-Seok Choi; Young-Sang Yu; Dong-Soo Han; Andreas Vogel; Lars Bocklage; Guido Meier; Mi-Young Im; Peter Fischer; Sang-Koog Kim

    2011-01-01

    A wide variety of coupled harmonic oscillators exist in nature. Coupling between different oscillators allows for the possibility of mutual energy transfer between them and the information-signal propagation. Low-energy input signals and their transport with negligible energy loss are the key technological factors in the design of information-signal processing devices. Here, utilizing the concept of coupled oscillators, we experimentally demonstrated a robust new mechanism for energy transfer...

  11. Signal sampling circuit

    NARCIS (Netherlands)

    Louwsma, S.M.; Vertregt, Maarten

    2011-01-01

    A sampling circuit for sampling a signal is disclosed. The sampling circuit comprises a plurality of sampling channels adapted to sample the signal in time-multiplexed fashion, each sampling channel comprising a respective track-and-hold circuit connected to a respective analogue to digital

  12. Signal sampling circuit

    NARCIS (Netherlands)

    Louwsma, S.M.; Vertregt, Maarten

    2010-01-01

    A sampling circuit for sampling a signal is disclosed. The sampling circuit comprises a plurality of sampling channels adapted to sample the signal in time-multiplexed fashion, each sampling channel comprising a respective track-and-hold circuit connected to a respective analogue to digital

  13. Ubiquitination in apoptosis signaling

    NARCIS (Netherlands)

    van de Kooij, L.W.

    2014-01-01

    The work described in this thesis focuses on ubiquitination and protein degradation, with an emphasis on how these processes regulate apoptosis signaling. More specifically, our aims were: 1. To increase the understanding of ubiquitin-mediated regulation of apoptosis signaling. 2. To identify the E3

  14. SignalR blueprints

    CERN Document Server

    Ingebrigtsen, Einar

    2015-01-01

    This book is designed for software developers, primarily those with knowledge of C#, .NET, and JavaScript. Good knowledge and understanding of SignalR is assumed to allow efficient programming of core elements and applications in SignalR.

  15. Optimal fault signal estimation

    NARCIS (Netherlands)

    Stoorvogel, Antonie Arij; Niemann, H.H.; Saberi, A.; Sannuti, P.

    2002-01-01

    We consider here both fault identification and fault signal estimation. Regarding fault identification, we seek either exact or almost fault identification. On the other hand, regarding fault signal estimation, we seek either $H_2$ optimal, $H_2$ suboptimal or Hinfinity suboptimal estimation. By

  16. Multiresolution signal decomposition schemes

    NARCIS (Netherlands)

    J. Goutsias (John); H.J.A.M. Heijmans (Henk)

    1998-01-01

    textabstract[PNA-R9810] Interest in multiresolution techniques for signal processing and analysis is increasing steadily. An important instance of such a technique is the so-called pyramid decomposition scheme. This report proposes a general axiomatic pyramid decomposition scheme for signal analysis

  17. The weight loss profile: a biopsychosocial approach to weight loss.

    Science.gov (United States)

    Feuerstein, M; Papciak, A; Shapiro, S; Tannenbaum, S

    1989-01-01

    Obesity is a common complicating condition in a variety of medical problems. Often effective consultation liaison involves recommendations to overweight patients involving lifestyle and health risk modification. Factors that need to be addressed include exercise, nutritional counseling/caloric restriction, and attitude and behavioral change regarding eating. Patients requiring weight loss typically seek various commercial programs that are readily accessible. One major problem associated with such programs is the high attrition rate within the first six weeks of initiation. Therefore, attempts to facilitate longer-term retention and associated weight loss are warranted. One approach is the identification of factors associated with problems in short-term retention and weight loss followed by the implementation of brief interventions to potentially reverse the influence of these factors on retention and weight loss. The present investigation was conducted to determine the effects of such a strategy on short-term retention and weight loss in a commercial weight loss program. Two groups (n = 66 per group) of female participants with a mean age of thirty-eight years, mean initial weight of 184.6 lbs, mean height of 64.3 inches, mean goal weight of 147.3 lbs, mean Body Mass Index of 31.4 kg/m2 were recruited for the study. Groups were matched for age, initial weight, height, goal weight, and body mass index. One group (controls) received a standard thirteen-week group cognitive-behavioral intervention that emphasized the teaching of self-management strategies for weight reduction. The second group (personalized intervention) received the same thirteen-week cognitive-behavioral intervention. This group also completed a questionnaire (Weight Loss Profile) that identifies factors associated with poor retention and minimal weight loss. Targeted interventions were implemented to modify specific problem areas identified on the Weight Loss Profile. The problem areas were based

  18. Neutron signal transfer analysis

    CERN Document Server

    Pleinert, H; Lehmann, E

    1999-01-01

    A new method called neutron signal transfer analysis has been developed for quantitative determination of hydrogenous distributions from neutron radiographic measurements. The technique is based on a model which describes the detector signal obtained in the measurement as a result of the action of three different mechanisms expressed by signal transfer functions. The explicit forms of the signal transfer functions are determined by Monte Carlo computer simulations and contain only the distribution as a variable. Therefore an unknown distribution can be determined from the detector signal by recursive iteration. This technique provides a simple and efficient tool for analysis of this type while also taking into account complex effects due to the energy dependency of neutron interaction and single and multiple scattering. Therefore this method provides an efficient tool for precise quantitative analysis using neutron radiography, as for example quantitative determination of moisture distributions in porous buil...

  19. Acoustic Signals and Systems

    DEFF Research Database (Denmark)

    2008-01-01

    The Handbook of Signal Processing in Acoustics will compile the techniques and applications of signal processing as they are used in the many varied areas of Acoustics. The Handbook will emphasize the interdisciplinary nature of signal processing in acoustics. Each Section of the Handbook...... will present topics on signal processing which are important in a specific area of acoustics. These will be of interest to specialists in these areas because they will be presented from their technical perspective, rather than a generic engineering approach to signal processing. Non-specialists, or specialists...... from different areas, will find the self-contained chapters accessible and will be interested in the similarities and differences between the approaches and techniques used in different areas of acoustics....

  20. Molecular and Cellular Signaling

    CERN Document Server

    Beckerman, Martin

    2005-01-01

    A small number of signaling pathways, no more than a dozen or so, form a control layer that is responsible for all signaling in and between cells of the human body. The signaling proteins belonging to the control layer determine what kinds of cells are made during development and how they function during adult life. Malfunctions in the proteins belonging to the control layer are responsible for a host of human diseases ranging from neurological disorders to cancers. Most drugs target components in the control layer, and difficulties in drug design are intimately related to the architecture of the control layer. Molecular and Cellular Signaling provides an introduction to molecular and cellular signaling in biological systems with an emphasis on the underlying physical principles. The text is aimed at upper-level undergraduates, graduate students and individuals in medicine and pharmacology interested in broadening their understanding of how cells regulate and coordinate their core activities and how diseases ...

  1. Loss and damage post Paris

    Science.gov (United States)

    Petherick, Anna

    2016-08-01

    The Paris Agreement gave the Warsaw International Mechanism for Loss and Damage a permanent and potentially prominent place in climate negotiations, but beyond that its impact remains wide open for interpretation.

  2. Dietary Supplements for Weight Loss

    Science.gov (United States)

    ... 2 • WEIGHT-LOSS SUPPLEMENTS FACT SHEET FOR CONSUMERS Bitter orange Bitter orange contains synephrine (a stimulant), and is claimed to ... breakdown of fat, and decrease appetite. Products with bitter orange usually also contain caffeine and other ingredients. Bitter ...

  3. Sudden hearing loss in children.

    Science.gov (United States)

    Ječmenica, Jovana; Bajec-Opančina, Aleksandra

    2014-08-01

    Sudden sensorineural hearing loss (SSHL) is defined as a unilateral or bilateral sensorineural hearing loss with at least 30 dB decrease in threshold in 3 contiguous test frequencies occurring over 72 hours or less. It is very rare in children. Sudden hearing loss is a symptom that suggests that there is a problem in the inner ear, surrounding structures, or the whole organism. The etiology and development of this disorder are still not fully understood. The literature contains numerous models of the pathogenesis of SSHL, with childhood SSHL having certain peculiarities. In practical terms, the multifactorial nature of SSHL is important in the choice of diagnostic methods and treatment methods. It is important to determine the cause and effect relationship between the underlying disease and hearing loss. © The Author(s) 2014.

  4. Fractional Transmission Line with Losses

    Science.gov (United States)

    Gómez-Aguilar, José Francisco; Dumitru, Baleanu

    2014-11-01

    In this manuscript, the fractional transmission line with losses is presented. The order of the Caputo derivative is considered as 0 Mittag-Leffler functions. The classic cases are recovered when β and γ are equal to 1.

  5. Hires and Losses Tracking System

    Data.gov (United States)

    Social Security Administration — This database contains data about the hires and losses of employees for the Office of Systems-those who join or leave the Office of Systems and those who transfer...

  6. Diet for rapid weight loss

    Science.gov (United States)

    ... each day. A VLCD is only recommended for adults who are obese and need to lose weight for health reasons. These diets are often used before weight-loss surgery. You should only use a VLCD with ...

  7. Bank loan loss provisions research: A review

    Directory of Open Access Journals (Sweden)

    Peterson K. Ozili

    2017-09-01

    Full Text Available We review the recent academic and policy literature on bank loan loss provisioning. Among other things, we observe that there exist some interaction between LLPs and existing prudential, accounting, institutional, cultural, religious, tax and fiscal frameworks which differ across countries; and we find that managerial discretion in provisioning is strongly linked to income smoothing, capital management, signalling, tax management and other objectives. We also address several issues including the ethical dimensions of income smoothing, factors influencing income smoothing, methodological issues in LLP modelling and the dynamic loan loss provisioning experiment; which opens up several avenues for further research such as: finding a balance between sufficient LLPs which regulators want versus transparent LLPs which standard setters want; the sensitivity of abnormal LLPs to changes in equity; the persistence of abnormal LLPs following CEO exit; country-specific interventions that induce LLP procyclicality in emerging countries; the impact of Basel III on banks' provisioning discretion; LLP behaviour among systemic and non-systemic financial institutions; etc. We conclude that regulators need to pay attention to how much discretion lending institutions should have in determining reported provision estimates, and this has been a long standing issue.

  8. Molecular basis of hair cell loss.

    Science.gov (United States)

    Furness, David N

    2015-07-01

    Mechanisms that lead to the death of hair cells are reviewed. Exposure to noise, the use of ototoxic drugs that damage the cochlea and old age are accompanied by hair cell death. Outer hair cells are often more susceptible than inner hair cells, partly because of an intrinsically greater susceptibility; high frequency cells are also more vulnerable. A common factor in hair cell loss following age-related changes and exposure to ototoxic drugs or high noise levels is the generation of reactive oxygen species, which can trigger intrinsic apoptosis (the mitochondrial pathway). However, hair cell death is sometimes produced via an extracellular signal pathway triggering extrinsic apoptosis. Necrosis and necroptosis also play a role and, in various situations in which cochlear damage occurs, a balance exists between these possible routes of cell death, with no one mechanism being exclusively activated. Finally, the numerous studies on these mechanisms of hair cell death have led to the identification of many potential therapeutic agents, some of which have been used to attempt to treat people exposed to damaging events, although clinical trials are not yet conclusive. Continued work in this area is likely to lead to clinical treatments that could be used to prevent or ameliorate hearing loss.

  9. Job loss and broken partnerships

    DEFF Research Database (Denmark)

    Kriegbaum, Margit; Christensen, Ulla; Lund, Rikke

    2008-01-01

    The aim of this study was to investigate the effects of the accumulated number of job losses and broken partnerships (defined as the end of cohabitation) on the risk of fatal and nonfatal events of ischemic heart disease (IHD).......The aim of this study was to investigate the effects of the accumulated number of job losses and broken partnerships (defined as the end of cohabitation) on the risk of fatal and nonfatal events of ischemic heart disease (IHD)....

  10. Weight Loss Strategies Utilized in a Men's Weight Loss Intervention.

    Science.gov (United States)

    Crane, Melissa M; Lutes, Lesley D; Sherwood, Nancy E; Ward, Dianne S; Tate, Deborah F

    2017-09-01

    Men are underrepresented in weight loss programs and little is currently known about the weight loss strategies men prefer. This study describes the weight loss strategies used by men during a men-only weight loss program. At baseline, 3 months, and 6 months, participants reported how frequently they used 45 weight loss strategies including strategies frequently recommended by the program (i.e., mentioned during every intervention contact; e.g., daily self-weighing), strategies occasionally recommended by the program (i.e., mentioned at least once during the program; e.g., reduce calories from beverages), and strategies not included in the program (e.g., increase daily steps). At baseline participants ( N = 107, 44.2 years, body mass index = 31.4 kg/m2, 76.6% White) reported regularly using 7.3 ± 6.6 ( M ± SD) strategies. The intervention group increased the number of strategies used to 19.1 ± 8.3 at 3 months and 17.1 ± 8.4 at 6 months with no changes in the waitlist group. The intervention group reported increased use of most of the strategies frequently recommended by the program (4 of 5), nearly half of the strategies occasionally recommended by the program (10 of 24), and one strategy not included in the program (of 16) at 6 months. The intervention effect at 6 months was significantly mediated by the number of strategies used at 3 months. This study adds to what is known about men's use of weight loss strategies prior to and during a formal weight loss program and will help future program developers create programs that are tailored to men.

  11. Comparative Study of Prestress Losses

    Directory of Open Access Journals (Sweden)

    M. Boukendakdji

    2017-06-01

    Full Text Available This paper compares the prestress losses as calculated by four different design codes; British standard CP110, Comite Europeen du Beton 70 and 78, American Concrete Institute 77 and the Prestressed Concrete Institute method (PCI. The comparison is done by determining the total losses which take place in a rectangular prestressed concrete beam for both pre-tensioning and post-tensioning systems. The results show that total losses calculated for the post-tensioning method are higher than those calculated for the pre-tensioning method, which is not the usual case. It seems that the PCI method may be required for special structures or for simply supported slender members which may be sensitive to small changes in deflections. However, for non-special structures, or where actual losses have little effect on the design, it is better to compute losses by the ACI method because it is simple and does take into considerations interactions between the various sources of losses. However, it is not possible to conclude which method gives the more accurate prediction of shrinkage and creep without direct co-relation to realistic insitu data.

  12. Feather loss in laying hens

    Directory of Open Access Journals (Sweden)

    Hristov Slavča

    2006-01-01

    Full Text Available The paper examined the incidence of different forms of feather loss and cannibalism in laying hens aged 74 weeks following moulting and in laying hens following exploitation for a period of one year. The forms of feather loss were considered in detail through a repeated examination of video recordings and they were sorted according to localization - to feather loss on the ventral part of the neck, on the dorsal part of the neck, and on the back between the wings. Feather loss on the ventral part of the neck was established in 47.9% hens, and in the dorsal part in 16.77% hens of the 167 laying hens aged 74 weeks following moulting. The group of 129 laying hens that were observed following one-year exploitation exhibited considerably more frequent feather loss, in 96.90% hens it was localized on the ventral part of the neck, in 60.47% hens on the dorsal part of the neck, and in 20.16% hens it was localized on the back between the wings. A comparison of the results of the incidence of co localized forms of feather loss in the one and the other group of laying hens using the t-test showed statistically very significant differences. A detailed consideration of the video recordings using the method of sequence analysis did not reveal any cannibalism in either group of laying hens.

  13. Age-related hair pigment loss.

    Science.gov (United States)

    Tobin, Desmond J

    2015-01-01

    Humans are social animals that communicate disproportionately via potent genetic signals imbued in the skin and hair, including racial, ethnic, health, gender, and age status. For the vast majority of us, age-related hair pigment loss becomes the inescapable signal of our disappearing youth. The hair follicle (HF) pigmentary unit is a wonderful tissue for studying mechanisms generally regulating aging, often before this becomes evident elsewhere in the body. Given that follicular melanocytes (unlike those in the epidermis) are regulated by the hair growth cycle, this cycle is likely to impact the process of aging in the HF pigmentary unit. The formal identification of melanocyte stem cells in the mouse skin has spurred a flurry of reports on the potential involvement of melanocyte stem cell depletion in hair graying (i.e., canities). Caution is recommended, however, against simple extrapolation of murine data to humans. Regardless, hair graying in both species is likely to involve an age-related imbalance in the tissue's oxidative stress handling that will impact not only melanogenesis but also melanocyte stem cell and melanocyte homeostasis and survival. There is some emerging evidence that the HF pigmentary unit may have regenerative potential, even after it has begun to produce white hair fibers. It may therefore be feasible to develop strategies to modulate some aging-associated changes to maintain melanin production for longer. © 2015 S. Karger AG, Basel.

  14. Microwave signal processing with photorefractive dynamic holography

    Science.gov (United States)

    Fotheringham, Edeline B.

    Have you ever found yourself listening to the music playing from the closest stereo rather than to the bromidic (uninspiring) person speaking to you? Your ears receive information from two sources but your brain listens to only one. What if your cell phone could distinguish among signals sharing the same bandwidth too? There would be no "full" channels to stop you from placing or receiving a call. This thesis presents a nonlinear optical circuit capable of distinguishing uncorrelated signals that have overlapping temporal bandwidths. This so called autotuning filter is the size of a U.S. quarter dollar and requires less than 3 mW of optical power to operate. It is basically an oscillator in which the losses are compensated with dynamic holographic gain. The combination of two photorefractive crystals in the resonator governs the filter's winner-take-all dynamics through signal-competition for gain. This physical circuit extracts what is mathematically referred to as the largest principal component of its spatio-temporal input space. The circuit's practicality is demonstrated by its incorporation in an RF-photonic system. An unknown mixture of unknown microwave signals, received by an antenna array, constitutes the input to the system. The output electronically returns one of the original microwave signals. The front-end of the system down converts the 10 GHz microwave signals and amplifies them before the signals phase modulate optical beams. The optical carrier is suppressed from these beams so that it may not be considered as a signal itself to the autotuning filter. The suppression is achieved with two-beam coupling in a single photorefractive crystal. The filter extracts the more intense of the signals present on the carrier-suppressed input beams. The detection of the extracted signal restores the microwave signal to an electronic form. The system, without the receiving antenna array, is packaged in a 13 x 18 x 6″ briefcase. Its power consumption equals that

  15. Shaping communicative colour signals over evolutionary time

    Science.gov (United States)

    Oyola Morales, José R.; Vital-García, Cuauhcihuatl; Hews, Diana K.; Martins, Emília P.

    2016-01-01

    Many evolutionary forces can shape the evolution of communicative signals, and the long-term impact of each force may depend on relative timing and magnitude. We use a phylogenetic analysis to infer the history of blue belly patches of Sceloporus lizards, and a detailed spectrophotometric analysis of four species to explore the specific forces shaping evolutionary change. We find that the ancestor of Sceloporus had blue patches. We then focus on four species; the first evolutionary shift (captured by comparison of S. merriami and S. siniferus) represents an ancient loss of the belly patch by S. siniferus, and the second evolutionary shift, bounded by S. undulatus and S. virgatus, represents a more recent loss of blue belly patch by S. virgatus. Conspicuousness measurements suggest that the species with the recent loss (S. virgatus) is the least conspicuous. Results for two other species (S. siniferus and S. merriami) suggest that over longer periods of evolutionary time, new signal colours have arisen which minimize absolute contrast with the habitat while maximizing conspicuousness to a lizard receiver. Specifically, males of the species representing an ancient loss of blue patch (S. siniferus) are more conspicuous than are females in the UV, whereas S. merriami males have evolved a green element that makes their belly patches highly sexually dimorphic but no more conspicuous than the white bellies of S. merriami females. Thus, our results suggest that natural selection may act more immediately to reduce conspicuousness, whereas sexual selection may have a more complex impact on communicative signals through the introduction of new colours. PMID:28018661

  16. Plant cytokinin signalling.

    Science.gov (United States)

    Keshishian, Erika A; Rashotte, Aaron M

    2015-01-01

    Cytokinin is an essential plant hormone that is involved in a wide range of plant growth and developmental processes which are controlled through its signalling pathway. Cytokinins are a class of molecules that are N(6)-substituted adenine derivatives, such as isopentenyl adenine, and trans- and cis-zeatin, which are common in most plants. The ability to perceive and respond to cytokinin occurs through a modified bacterial two-component pathway that functions via a multi-step phosphorelay. This cytokinin signalling process is a crucial part of almost all stages of plant life, from embryo patterning to apical meristem regulation, organ development and eventually senescence. The cytokinin signalling pathway involves the co-ordination of three types of proteins: histidine kinase receptors to perceive the signal, histidine phosphotransfer proteins to relay the signal, and response regulators to provide signal output. This pathway contains both positive and negative elements that function in a complex co-ordinated manner to control cytokinin-regulated plant responses. Although much is known about how this cytokinin signal is perceived and initially regulated, there are still many avenues that need to be explored before the role of cytokinin in the control of plant processes is fully understood. © 2015 Authors; published by Portland Press Limited.

  17. Aberrant activation of notch signaling in human breast cancer.

    Science.gov (United States)

    Stylianou, Spyros; Clarke, Rob B; Brennan, Keith

    2006-02-01

    A role for Notch signaling in human breast cancer has been suggested by both the development of adenocarcinomas in the murine mammary gland following pathway activation and the loss of Numb expression, a negative regulator of the Notch pathway, in a large proportion of breast carcinomas. However, it is not clear currently whether Notch signaling is frequently activated in breast tumors, and how it causes cellular transformation. Here, we show accumulation of the intracellular domain of Notch1 and hence increased Notch signaling in a wide variety of human breast carcinomas. In addition, we show that increased RBP-Jkappa-dependent Notch signaling is sufficient to transform normal breast epithelial cells and that the mechanism of transformation is most likely through the suppression of apoptosis. More significantly, we show that attenuation of Notch signaling reverts the transformed phenotype of human breast cancer cell lines, suggesting that inhibition of Notch signaling may be a therapeutic strategy for this disease.

  18. Hippo Reprograms the Transcriptional Response to Ras Signaling.

    Science.gov (United States)

    Pascual, Justine; Jacobs, Jelle; Sansores-Garcia, Leticia; Natarajan, Malini; Zeitlinger, Julia; Aerts, Stein; Halder, Georg; Hamaratoglu, Fisun

    2017-09-25

    Hyperactivating mutations in Ras signaling are hallmarks of carcinomas. Ras signaling mediates cell fate decisions as well as proliferation during development. It is not known what dictates whether Ras signaling drives differentiation versus proliferation. Here we show that the Hippo pathway is critical for this decision. Loss of Hippo switches Ras activation from promoting cellular differentiation to aggressive cellular proliferation. Transcriptome analysis combined with genetic tests show that this excessive proliferation depends on the synergistic induction of Ras target genes. Using ChIP-nexus, we find that Hippo signaling keeps Ras targets in check by directly regulating the expression of two key downstream transcription factors of Ras signaling: the ETS-domain transcription factor Pointed and the repressor Capicua. Our results highlight how independent signaling pathways can impinge on each other at the level of transcription factors, thereby providing a safety mechanism to keep proliferation in check under normal developmental conditions. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Comparative Analysis of Path Loss Prediction Models for Urban ...

    African Journals Online (AJOL)

    ... Egli were 16.24dB, 2.37dB and 8.40dB respectively. The results showed that Hata's model is the most accurate and reliable path loss prediction model for macrocellular urban propagation environments, since its MSE value of 2.37dB is smaller than the acceptable minimum MSE value of 6dB for good signal propagation.

  20. Guard Cell Signal Transduction Network: Advances in Understanding Abscisic Acid, CO2, and Ca2+ Signaling

    KAUST Repository

    Kim, Tae-Houn

    2010-05-04

    Stomatal pores are formed by pairs of specialized epidermal guard cells and serve as major gateways for both CO2 influx into plants from the atmosphere and transpirational water loss of plants. Because they regulate stomatal pore apertures via integration of both endogenous hormonal stimuli and environmental signals, guard cells have been highly developed as a model system to dissect the dynamics and mechanisms of plant-cell signaling. The stress hormone ABA and elevated levels of CO2 activate complex signaling pathways in guard cells that are mediated by kinases/phosphatases, secondary messengers, and ion channel regulation. Recent research in guard cells has led to a new hypothesis for how plants achieve specificity in intracellular calcium signaling: CO2 and ABA enhance (prime) the calcium sensitivity of downstream calcium-signaling mechanisms. Recent progress in identification of early stomatal signaling components are reviewed here, including ABA receptors and CO2-binding response proteins, as well as systems approaches that advance our understanding of guard cell-signaling mechanisms.

  1. Bmp signaling mediates endoderm pouch morphogenesis by regulating Fgf signaling in zebrafish.

    Science.gov (United States)

    Lovely, C Ben; Swartz, Mary E; McCarthy, Neil; Norrie, Jacqueline L; Eberhart, Johann K

    2016-06-01

    The endodermal pouches are a series of reiterated structures that segment the pharyngeal arches and help pattern the vertebrate face. Multiple pathways regulate the complex process of endodermal development, including the Bone morphogenetic protein (Bmp) pathway. However, the role of Bmp signaling in pouch morphogenesis is poorly understood. Using genetic and chemical inhibitor approaches, we show that pouch morphogenesis requires Bmp signaling from 10-18 h post-fertilization, immediately following gastrulation. Blocking Bmp signaling during this window results in morphological defects to the pouches and craniofacial skeleton. Using genetic chimeras we show that Bmp signals directly to the endoderm for proper morphogenesis. Time-lapse imaging and analysis of reporter transgenics show that Bmp signaling is necessary for pouch outpocketing via the Fibroblast growth factor (Fgf) pathway. Double loss-of-function analyses demonstrate that Bmp and Fgf signaling interact synergistically in craniofacial development. Collectively, our analyses shed light on the tissue and signaling interactions that regulate development of the vertebrate face. © 2016. Published by The Company of Biologists Ltd.

  2. A Versatile Beam Loss Monitoring System for CLIC

    CERN Document Server

    Kastriotou, Maria; Farabolini, Wilfrid; Holzer, Eva Barbara; Nebot Del Busto, Eduardo; Tecker, Frank; Welsch, Carsten

    2016-01-01

    The design of a potential CLIC beam loss monitoring (BLM) system presents multiple challenges. To successfully cover the 48 km of beamline, ionisation chambers and optical fibre BLMs are under investigation. The former fulfils all CLIC requirements but would need more than 40000 monitors to protect the whole facility. For the latter, the capability of reconstructing the original loss position with a multi-bunch beam pulse and multiple loss locations still needs to be quantified. Two main sources of background for beam loss measurements are identified for CLIC. The two-beam accelerator scheme introduces so-called crosstalk, i.e. detection of losses originating in one beam line by the monitors protecting the other. Moreover, electrons emitted from the inner surface of RF cavities and boosted by the high RF gradients may produce signals in neighbouring BLMs, limiting their ability to detect real beam losses. This contribution presents the results of dedicated experiments performed in the CLIC Test Facility to qu...

  3. High-Rate Strong-Signal Quantum Cryptography

    Science.gov (United States)

    Yuen, Horace P.

    1996-01-01

    Several quantum cryptosystems utilizing different kinds of nonclassical lights, which can accommodate high intensity fields and high data rate, are described. However, they are all sensitive to loss and both the high rate and the strong-signal character rapidly disappear. A squeezed light homodyne detection scheme is proposed which, with present-day technology, leads to more than two orders of magnitude data rate improvement over other current experimental systems for moderate loss.

  4. Signal Identification and Isolation Utilizing Radio Frequency Photonics

    Science.gov (United States)

    2017-09-01

    frequency can be obtained. The block diagram appears in Figure 3. Another type of photonic spectrum analyzer has been developed based on rare earth doped...by using a feedback loop of a fixed delay. In this case, the signal will ideally be a summation of an infinite number of delay round trips. While...this is hard to realize in the electronic domain, the low loss of fiber can provide multiple round trips without a large amount of loss. An example of

  5. Signal flow analysis

    CERN Document Server

    Abrahams, J R; Hiller, N

    1965-01-01

    Signal Flow Analysis provides information pertinent to the fundamental aspects of signal flow analysis. This book discusses the basic theory of signal flow graphs and shows their relation to the usual algebraic equations.Organized into seven chapters, this book begins with an overview of properties of a flow graph. This text then demonstrates how flow graphs can be applied to a wide range of electrical circuits that do not involve amplification. Other chapters deal with the parameters as well as circuit applications of transistors. This book discusses as well the variety of circuits using ther

  6. Recurrent pregnancy loss: current perspectives

    Directory of Open Access Journals (Sweden)

    El Hachem H

    2017-05-01

    Full Text Available Hady El Hachem,1,2 Vincent Crepaux,3 Pascale May-Panloup,4 Philippe Descamps,3 Guillaume Legendre,3 Pierre-Emmanuel Bouet3 1Department of Reproductive Medicine, Ovo Clinic, Montréal, QC, Canada; 2Department of Obstetrics and Gynecology, University of Montreal, Montréal, QC, Canada; 3Department of Obstetrics and Gynecology, Angers University Hopsital, Angers, France; 4Department of Reproductive Biology, Angers University Hospital, Angers, France Abstract: Recurrent pregnancy loss is an important reproductive health issue, affecting 2%–5% of couples. Common established causes include uterine anomalies, antiphospholipid syndrome, hormonal and metabolic disorders, and cytogenetic abnormalities. Other etiologies have been proposed but are still considered controversial, such as chronic endometritis, inherited thrombophilias, luteal phase deficiency, and high sperm DNA fragmentation levels. Over the years, evidence-based treatments such as surgical correction of uterine anomalies or aspirin and heparin for antiphospholipid syndrome have improved the outcomes for couples with recurrent pregnancy loss. However, almost half of the cases remain unexplained and are empirically treated using progesterone supplementation, anticoagulation, and/or immunomodulatory treatments. Regardless of the cause, the long-term prognosis of couples with recurrent pregnancy loss is good, and most eventually achieve a healthy live birth. However, multiple pregnancy losses can have a significant psychological toll on affected couples, and many efforts are being made to improve treatments and decrease the time needed to achieve a successful pregnancy. This article reviews the established and controversial etiologies, and the recommended therapeutic strategies, with a special focus on unexplained recurrent pregnancy losses and the empiric treatments used nowadays. It also discusses the current role of preimplantation genetic testing in the management of recurrent pregnancy

  7. A Prototype Readout System for the Diamond Beam Loss Monitors at LHC

    CERN Document Server

    Effinger, E; Baer, T; Schmidt, R; Frais-Kölbl, H; Griesmayer, E; Kavrigin, P; CERN. Geneva. ATS Department

    2013-01-01

    Diamond Beam Loss Monitors are used at the LHC for the measurement of fast beam losses. In this note, specimen LHC loss measurements with the prototype readout system “ROSY” from CIVIDEC are presented. The readout system is FPGA-based for on-line, real-time, and dead-time-free data processing, including a Linux-based server for the interconnection to a GUI. The loss analysis makes full use of the fast signal response of the diamond detectors with 1 ns time resolution and 6.7 ns double pulse resolution. Two examples are presented: applications of the Time Loss Histogram with 1.6 ns binning and 1.2 ns time jitter for loss measurements that are synchronized with the LHC revolution period and a beam-loss-based tune measurement for all circulating bunches in parallel.

  8. Time Encoded Signal Processing for Speech Quality Assessment

    OpenAIRE

    Kraljevski, Ivan; Stojanovic, Igor; Chungurski, Slavco; Arsenovski, Sime

    2010-01-01

    In this paper a method for speech quality assessment is described and evaluated simulating transmission of AMR-NB encoded speech over noisy GSM channel. The proposed system uses comparison of Time Encoded Signal (TES) processing of speech sequences, where one original and one degraded speech signal were transmitted trough GSM simulation system with AWGN noise channel. Several tests have been made on reference speech sample of single speaker with simulated bit-error loss effects on the perc...

  9. Frequency resolution and hearing loss.

    Science.gov (United States)

    Tyler, R S; Wood, E J; Fernandes, M

    1982-02-01

    Future scientific and diagnostic interest in frequency resolution requires an evaluation of the different methods that are available to measure it. We compared three methods: (1) pure-tone thresholds in broadband noise, (2) pure-tone thresholds in the presence of a fixed pure-tone masker and (3) psychoacoustical tuning curves. We additionally obtained estimates of temporal integration and of speech intelligibility in noise. Three subject groups were tested: 10 normals, 13 subjects with a noise-induced hearing loss and 18 subjects with a cochlear hearing loss but no history of noise exposure. Generally the three measures of frequency resolution show moderate agreement with each other. Poor frequency resolution is invariably associated with a pure-tone threshold loss. Temporal integration appears unrelated either to the pure-tone threshold loss or frequency resolution. Some of the measures of frequency resolution display significant correlation with speech intelligibility in noise. However, since both variables are correlated with pure-tone threshold loss the exact relationship between frequency resolution and speech intelligibility cannot be clearly established.

  10. [Hearing loss and Alzheimer's disease].

    Science.gov (United States)

    Bakhos, David; Villeuneuve, Alexandre; Kim, Soo; Hammoudi, Karim; Hommet, Caroline

    2015-06-01

    Recent studies suggest that subjects with hearing loss are more likely to develop Alzheimer's disease. Hearing loss can be consecutive to presbycusis and/or to central auditory dysfunction. Standard audiometric measures (pure tone and speech intelligibility) allow the diagnosis of presbycusis. However, to demonstrate central auditory dysfunction, specific audiometric tests are needed such as noisy and/or dichotic tests. Actually, no consensus exists to investigate hearing loss in people with Alzheimer's disease though hearing loss may be an early manifestation of Alzheimer's disease. Until now, investigations and clinical procedure related to the diagnosis of Alzheimer's disease ignored the hearing ability of the patient. However, the major part of care management and investigations implies the patient's communication ability with the caregivers. Hearing loss may be one of the most unrecognized deficit in subjects with Alzheimer's disease. Auditory rehabilitation could benefit to the patient in order to lessen cognitive decline, but this must be investigated during longitudinal studies in order to clearly demonstrate their efficiency.

  11. Effectiveness of Wavelet Denoising on Electroencephalogram Signals

    Directory of Open Access Journals (Sweden)

    Md. Mamun

    2013-01-01

    Full Text Available Analyzing Electroencephalogram (EEG signal is a challenge due to the various artifacts used by Electromyogram,eye blink and Electrooculogram. The present de-noising techniques that are based on the frequency selective filteringsuffers from a substantial loss of the EEG data. Noise removal using wavelet has the characteristic of preservingsignal uniqueness even if noise is going to be minimized. To remove noise from EEG signal, this research employeddiscrete wavelet transform. Root mean square difference has been used to find the usefulness of the noiseelimination. In this research, four different discrete wavelet functions have been used to remove noise from theElectroencephalogram signal gotten from two different types of patients (healthy and epileptic to show theeffectiveness of DWT on EEG noise removal. The result shows that the WF orthogonal meyer is the best one fornoise elimination from the EEG signal of epileptic subjects and the WF Daubechies 8 (db8 is the best one for noiseelimination from the EEG signal on healthy subjects.

  12. Signal Station Inspection Reports

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Handwritten reports resulting from detailed inspections of US Army Signal Service Stations, 1871-1889. Features reported included instrument exposure and condition,...

  13. Transmembrane Signalling: Membrane messengers

    Science.gov (United States)

    Cockroft, Scott L.

    2017-05-01

    Life has evolved elaborate means of communicating essential chemical information across cell membranes. Inspired by biology, two new artificial mechanisms have now been developed that use synthetic messenger molecules to relay chemical signals into or across lipid membranes.

  14. Topological signal processing

    CERN Document Server

    Robinson, Michael

    2014-01-01

    Signal processing is the discipline of extracting information from collections of measurements. To be effective, the measurements must be organized and then filtered, detected, or transformed to expose the desired information.  Distortions caused by uncertainty, noise, and clutter degrade the performance of practical signal processing systems. In aggressively uncertain situations, the full truth about an underlying signal cannot be known.  This book develops the theory and practice of signal processing systems for these situations that extract useful, qualitative information using the mathematics of topology -- the study of spaces under continuous transformations.  Since the collection of continuous transformations is large and varied, tools which are topologically-motivated are automatically insensitive to substantial distortion. The target audience comprises practitioners as well as researchers, but the book may also be beneficial for graduate students.

  15. Foundations of signal processing

    CERN Document Server

    Vetterli, Martin; Goyal, Vivek K

    2014-01-01

    This comprehensive and engaging textbook introduces the basic principles and techniques of signal processing, from the fundamental ideas of signals and systems theory to real-world applications. Students are introduced to the powerful foundations of modern signal processing, including the basic geometry of Hilbert space, the mathematics of Fourier transforms, and essentials of sampling, interpolation, approximation and compression. The authors discuss real-world issues and hurdles to using these tools, and ways of adapting them to overcome problems of finiteness and localisation, the limitations of uncertainty and computational costs. Standard engineering notation is used throughout, making mathematical examples easy for students to follow, understand and apply. It includes over 150 homework problems and over 180 worked examples, specifically designed to test and expand students' understanding of the fundamentals of signal processing, and is accompanied by extensive online materials designed to aid learning, ...

  16. Acoustic MIMO signal processing

    CERN Document Server

    Huang, Yiteng; Chen, Jingdong

    2006-01-01

    A timely and important book addressing a variety of acoustic signal processing problems under multiple-input multiple-output (MIMO) scenarios. It uniquely investigates these problems within a unified framework offering a novel and penetrating analysis.

  17. Traffic Signal Cycle Lengths

    Data.gov (United States)

    Town of Chapel Hill, North Carolina — Traffic signal location list for the town of Chapel Hill. This data set includes light cycle information as well as as intersection information.The Town of Chapel...

  18. Ultrahigh bandwidth signal processing

    DEFF Research Database (Denmark)

    Oxenløwe, Leif Katsuo

    2016-01-01

    Optical time lenses have proven to be very versatile for advanced optical signal processing. Based on a controlled interplay between dispersion and phase-modulation by e.g. four-wave mixing, the processing is phase-preserving, an hence useful for all types of data signals including coherent multi......-level modulation founats. This has enabled processing of phase-modulated spectrally efficient data signals, such as orthogonal frequency division multiplexed (OFDM) signa In that case, a spectral telescope system was used, using two time lenses with different focal lengths (chirp rates), yielding a spectral...... regeneratio These operations require a broad bandwidth nonlinear platform, and novel photonic integrated nonlinear platform like aluminum gallium arsenide nano-waveguides used for 1.28 Tbaud optical signal processing will be described....

  19. The LHC beam loss monitoring system's data acquisition card

    CERN Document Server

    Effinger, E; Emery, J; Ferioli, G; Gauglio, G; Zamantzas, C

    2007-01-01

    The beam loss monitoring (BLM) system [1] of the LHC is one of the most critical elements for the protection of the LHC. It must prevent the super conducting magnets from quenches and the machine components from damages, caused by beam losses. Ionization chambers and secondary emission based beam loss detectors are used on several locations around the ring. The sensors are producing a signal current, which is related to the losses. This current will be measured by a tunnel electronic, which acquires, digitizes and transmits the data via an optical link to the surface electronic. The so called threshold comparator (TC) [2] collects, analyzes and compares the data with threshold table. It also gives a dump signal through the combiner card to the beam inter lock system (BIC). The usage of the system, for protection and tuning of the LHC and the scale of the LHC, imposed exceptional specification of the dynamic range and radiation tolerance. The input current dynamic range should allow measurements between 10pA a...

  20. Modest Advertising Signals Strength.

    OpenAIRE

    Ram Orzach; Per Baltzer Overgaard; Yair Tauman

    2001-01-01

    This paper presents a signaling model where both price and advertising expenditures are used as signals of the initially unobservable quality of a newly introduced experience good. Consumers can be either "fastidious" or "indifferent". Fastidious individuals place a greater value on a high-quality product and a lesser value on the low-quality product than do indifferent individuals. It is shown that a sensible separating equilibrium exists where both firms set their full information prices. H...

  1. Lipid Signaling in Tumorigenesis

    OpenAIRE

    Liu, Renyan; Huang, Ying

    2014-01-01

    Lipids are important cellular building blocks and components of signaling cascades. Deregulation of lipid metabolism or signaling is frequently linked to a variety of human diseases such as diabetes, cardiovascular diseases, and cancer. It is widely believed that lipid molecules or their metabolic products are involved in tumorigenic inflammation and thus, lipids are implicated as significant contributors or even primary triggers of tumorigenesis. Lipids are believed to directly or indirectly...

  2. Optical Signal Processing.

    Science.gov (United States)

    1983-11-30

    that the readaptation phenomena is minimized as signal components leave the tap weight plane (the accumulator). In principle, the performance could be...accumulators so that the readaptation phenomena caused by large values pleaving the accumulator are minimized. Several examples of the performance...the jammer signal. The system then goes into a " readaptation " phase where the new contributions to the tap weights must offset the older cont

  3. Canonical Wnt Signaling Regulates Atrioventricular Junction Programming and Electrophysiological Properties

    Science.gov (United States)

    Gillers, Benjamin S; Chiplunkar, Aditi; Aly, Haytham; Valenta, Tomas; Basler, Konrad; Christoffels, Vincent M.; Efimov, Igor R; Boukens, Bastiaan J; Rentschler, Stacey

    2014-01-01

    Rationale Proper patterning of the atrioventricular canal (AVC) is essential for delay of electrical impulses between atria and ventricles, and defects in AVC maturation can result in congenital heart disease. Objective To determine the role of canonical Wnt signaling in the myocardium during AVC development. Methods and Results We utilized a novel allele of β-catenin that preserves β-catenin’s cell adhesive functions but disrupts canonical Wnt signaling, allowing us to probe the effects of Wnt loss of function independently. We show that loss of canonical Wnt signaling in the myocardium results in tricuspid atresia with hypoplastic right ventricle associated with loss of AVC myocardium. In contrast, ectopic activation of Wnt signaling was sufficient to induce formation of ectopic AV junction-like tissue as assessed by morphology, gene expression, and electrophysiologic criteria. Aberrant AVC development can lead to ventricular preexcitation, a characteristic feature of Wolff-Parkinson-White syndrome. We demonstrate that postnatal activation of Notch signaling downregulates canonical Wnt targets within the AV junction. Stabilization of β-catenin protein levels can rescue Notch-mediated ventricular preexcitation and dysregulated ion channel gene expression. Conclusions Our data demonstrate that myocardial canonical Wnt signaling is an important regulator of AVC maturation and electrical programming upstream of Tbx3. Our data further suggests that ventricular preexcitation may require both morphologic patterning defects, as well as myocardial lineage reprogramming, to allow robust conduction across accessory pathway tissue. PMID:25599332

  4. Complicated grief after perinatal loss.

    Science.gov (United States)

    Kersting, Anette; Wagner, Birgit

    2012-06-01

    The loss of an infant through stillbirth, miscarriage, or neonatal death is recognized as a traumatic life event. Predictors of development of complicated grief after prenatal loss include lack of social support, pre-existing relationship difficulties, or absence of surviving children, as well as ambivalent attitudes or heightened perception of the reality of the pregnancy. Risk of complicated grief was found to be especially high after termination of a pregnancy due to fetal abnormality. Studies have revealed that men and women show different patterns of grief, potentially exacerbating decline in a relationship. Although it is clear that prenatal loss has a large psychological impact, it is concluded that there is a substantial lack of randomized controlled studies in this field of research.

  5. Economic inequality predicts biodiversity loss.

    Directory of Open Access Journals (Sweden)

    Gregory M Mikkelson

    Full Text Available Human activity is causing high rates of biodiversity loss. Yet, surprisingly little is known about the extent to which socioeconomic factors exacerbate or ameliorate our impacts on biological diversity. One such factor, economic inequality, has been shown to affect public health, and has been linked to environmental problems in general. We tested how strongly economic inequality is related to biodiversity loss in particular. We found that among countries, and among US states, the number of species that are threatened or declining increases substantially with the Gini ratio of income inequality. At both levels of analysis, the connection between income inequality and biodiversity loss persists after controlling for biophysical conditions, human population size, and per capita GDP or income. Future research should explore potential mechanisms behind this equality-biodiversity relationship. Our results suggest that economic reforms would go hand in hand with, if not serving as a prerequisite for, effective conservation.

  6. Hearing loss at work? Hearing loss from leisure activities?

    CERN Multimedia

    2006-01-01

    The nurses of the Medical Service would like invite all persons working on the CERN site to take part in a: HEARING LOSS DETECTION WEEK From 28 August to 1st September 2006 At the Infirmary, Building 57 from 9 a.m. to 4 p.m. Hearing tests - advice - information - documentation - protective equipment

  7. Soil loss prediction using universal soil loss equation (USLE ...

    African Journals Online (AJOL)

    USER

    2010-06-14

    Jun 14, 2010 ... Land degradation and soil loss is a global event. Human induced pressures on the natural ecosystems are still in progress as well as conservation efforts. The need for sufficient knowledge and data for decision makers is obvious hence the present study was carried out. The study area, the Ağlasun district ...

  8. Management of hair loss diseases

    Directory of Open Access Journals (Sweden)

    Manabu Ohyama

    2010-12-01

    Full Text Available The treatment of hair loss diseases is sometimes difficult because of insufficient efficacy and limited options. However, recent advances in understanding of the pathophysiology and development of new remedies have improved the treatment of refractory hair loss conditions. In this article, an update on the management of hair loss diseases is provided, especially focusing on recently reported therapeutic approaches for alopecia areata (AA. An accurate diagnosis is indispensable to optimize treatment. Dry dermoscopy represents new diagnostic techniques, which could enable the differentiation of barely indistinguishable alopecias, e.g. AA and trichotillomania. An organized scalp biopsy adopting both vertical and transverse sectioning approaches also provides a deep insight into the pathophysiology of ongoing alopecias. Among various treatments for AA, intraregional corticosteroid and contact immunotherapy have been recognized as first-line therapies. However, some AA cases are refractory to both treatments. Recent studies have demonstrated the efficacy of pulse corticosteroid therapy or the combination of oral psoralen ultraviolet A therapy and systemic corticosteroids for severe AA. Previous clinical observations have suggested the potential role of antihistamines as supportive medications for AA. Experimental evaluation using AA model mice further supports their effectiveness in AA treatment. Finasteride opens up new possibilities for the treatment of androgenetic alopecia. For androgenetic alopecia patients refractory to finasteride, the combination of finasteride with topical minoxidil or the administration of dutasteride, another 5 alpha-reductase inhibitor, may provide better outcomes. Scarring alopecia is the most difficult form of hair loss disorder to treat. The bulge stem cell area is destroyed by unnecessary immune reactions with resultant permanent loss of hair follicle structures in scarring alopecia. Currently, treatment options for

  9. Digital Signal Processing applied to Physical Signals

    CERN Document Server

    Alberto, Diego; Musa, L

    2011-01-01

    It is well known that many of the scientific and technological discoveries of the XXI century will depend on the capability of processing and understanding a huge quantity of data. With the advent of the digital era, a fully digital and automated treatment can be designed and performed. From data mining to data compression, from signal elaboration to noise reduction, a processing is essential to manage and enhance features of interest after every data acquisition (DAQ) session. In the near future, science will go towards interdisciplinary research. In this work there will be given an example of the application of signal processing to different fields of Physics from nuclear particle detectors to biomedical examinations. In Chapter 1 a brief description of the collaborations that allowed this thesis is given, together with a list of the publications co-produced by the author in these three years. The most important notations, definitions and acronyms used in the work are also provided. In Chapter 2, the last r...

  10. Long-term weight loss maintenance

    National Research Council Canada - National Science Library

    Wing, Rena R; Phelan, Suzanne

    2005-01-01

    ...% of initial body weight and maintaining the loss for at least 1 y. The National Weight Control Registry provides information about the strategies used by successful weight loss maintainers to achieve and maintain long-term weight loss...

  11. Synthetic signal injection using a single RF channel

    Science.gov (United States)

    Marro, Kenneth I; Lee, Donghoon; Shankland, Eric G.; Mathis, Clinton M.; Hayes, Cecil E.

    2011-01-01

    Purpose To demonstrate that, when injecting an artificial reference signal for quantitation purposes, the real and artificial signals can be acquired separately, using a single RF channel, with no loss of fidelity. Conversion of MR signals to units of concentration can be simplified by injection of a precalibrated, artificial reference signal, or pseudo-signal. In previous implementations, the pseudo-signal was acquired simultaneously with the real signals arising from the sample and this requires a second, integrated RF channel. Materials and Methods We used in vivo spectroscopy and in vitro imaging measurements to test the validity of the separate acquisition method. Results There was very strong correlation (r = 0.94, p = 0.02) between the in vivo concentrations determined with separate and simultaneous acquisition methods. The in vitro measurements validated that the separate acquisition method compensates for differences in coil loading conditions as well as the simultaneous acquisition method. Conclusion Separate acquisition eliminates the need for a second RF channel, which allows easier implementation at sites that have only one channel available, and relaxes the constraints on the number and amplitude of pseudo-signals. This flexibility can be exploited to increase the signal to noise ratio of the pseudo-signal and reduce variability when making the conversion to units of concentration. PMID:22113992

  12. Synthetic signal injection using a single radiofrequency channel.

    Science.gov (United States)

    Marro, Kenneth I; Lee, Donghoon; Shankland, Eric G; Mathis, Clinton M; Hayes, Cecil E

    2011-12-01

    To demonstrate that, when injecting an artificial reference signal for quantitation purposes, the real and artificial signals can be acquired separately, using a single radiofrequency (RF) channel, with no loss of fidelity. Conversion of MR signals to units of concentration can be simplified by injection of a precalibrated, artificial reference signal, or pseudo-signal. In previous implementations, the pseudo-signal was acquired simultaneously with the real signals arising from the sample and this requires a second, integrated RF channel. We used in vivo spectroscopy and in vitro imaging measurements to test the validity of the separate acquisition method. There was very strong correlation (r = 0.94; P = 0.02) between the in vivo concentrations determined with separate and simultaneous acquisition methods. The in vitro measurements validated that the separate acquisition method compensates for differences in coil loading conditions as well as the simultaneous acquisition method. Separate acquisition eliminates the need for a second RF channel, which allows easier implementation at sites that have only one channel available, and relaxes the constraints on the number and amplitude of pseudo-signals. This flexibility can be exploited to increase the signal to noise ratio of the pseudo-signal and reduce variability when making the conversion to units of concentration. Copyright © 2011 Wiley Periodicals, Inc.

  13. Age-related hearing loss

    Science.gov (United States)

    ... everyday function. The following may be helpful: Hearing aids Telephone amplifiers and other assistive devices Sign language (for those with severe hearing loss) Speech reading (lip reading and using visual cues to aid communication) A cochlear implant may be recommended for people ...

  14. Abandoning weight-loss programmes

    African Journals Online (AJOL)

    the weight-loss programme. The facilitator of the discu.ssion groups, a clinical psychologist, asked only non-directive ques- tions and ensured participation of all members in the group. For every 4 panicipants a silent and non-panicipant observer recorded contributions. Group members formed a circle and silent observers ...

  15. Pressure losses in pneumatic transport

    NARCIS (Netherlands)

    Ottjes, J.A.

    1982-01-01

    A model is derived to calculate the pressure losses originating from the dilute phase pneumatic transport of coarse particles in the horizontal stationary flow regime. The model is based on the balance of drag forces and frictional forces acting on the particles during pneumatic transport. The

  16. Exploring Friendship Loss through Poetry

    Science.gov (United States)

    Furman, Rich

    2004-01-01

    Losing friendships are significant events for people throughout their life span. In spite of the importance of friendships to psychosocial health, studies of friendships loss are not found in the literature. This article begins to address this gap through a qualitative study utilizing autobiographical poetry as data. This study exemplifies…

  17. Noise-induced hearing loss

    Energy Technology Data Exchange (ETDEWEB)

    Catlin, F.I.

    1986-03-01

    Hearing loss affects 30 million people in the United States; of these, 21 million are over the age of 65 years. This disorder may have several causes: heredity, noise, aging, and disease. Hearing loss from noise has been recognized for centuries but was generally ignored until some time after the Industrial Revolution. Hearing loss from occupational exposure to hazardous noise was identified as a compensable disability by the United States courts in 1948 to 1959. Development of noisy jet engines and supersonic aircraft created additional claims for personal and property damage in the 1950s and 1960s. These conditions led to legislation for noise control in the form of the Occupational Safety and Health Act of 1970 and the Noise Control Act of 1972. Protection of the noise-exposed employee was also an objective of the Hearing Conservation Act of 1971. Subsequent studies have confirmed the benefits of periodic hearing tests for workers exposed to hazardous noise and of otologic evaluation as part of the hearing conservation process. Research studies in laboratory animals, using scanning electron microscopical techniques, have demonstrated that damage to the inner ear and organ of hearing can occur even though subjective (conditioned) response to sound stimuli remains unaffected. Some investigators have employed an epidemiologic approach to identify risk factors and to develop profiles to susceptibility to noise-induced hearing loss. The need for joint involvement of workers and employers in the reduction and control of occupational noise hazards is evident. 19 references.

  18. Intellectual Disabilities and Hearing Loss

    Science.gov (United States)

    Herer, Gilbert R.

    2012-01-01

    Undetected/untreated hearing loss imposes significant limitations upon individuals with intellectual disabilities (ID). It can interfere with cognitive development, impede communicative and social interactions, and limit vocational aspirations. Over the past decade, the hearing of 9961 people with ID was evaluated at Special Olympics sports…

  19. FTO genotype and weight loss

    DEFF Research Database (Denmark)

    Livingstone, Katherine M; Celis-Morales, Carlos; Papandonatos, George D

    2016-01-01

    OBJECTIVE: To assess the effect of the FTO genotype on weight loss after dietary, physical activity, or drug based interventions in randomised controlled trials. DESIGN: Systematic review and random effects meta-analysis of individual participant data from randomised controlled trials. DATA SOURC...

  20. Interface losses in multimaterial resonators

    DEFF Research Database (Denmark)

    Villanueva, L.G.; Amato, B.; Larsen, Tom

    2014-01-01

    We present an extensive study shedding light on the role of surface and bulk losses in micromechanical resonators. We fabricate thin silicon nitride membranes of different sizes and we coat them with different thicknesses of metal. We later characterize the 81 lowest out-of-plane flexural vibrati...

  1. Respiration signals from photoplethysmography.

    Science.gov (United States)

    Nilsson, Lena M

    2013-10-01

    Pulse oximetry is based on the technique of photoplethysmography (PPG) wherein light transmitted through tissues is modulated by the pulse. In addition to variations in light modulation by the cardiac cycle, the PPG signal contains a respiratory modulation and variations associated with changing tissue blood volume of other origins. Cardiovascular, respiratory, and neural fluctuations in the PPG signal are of different frequencies and can all be characterized according to their sinusoidal components. PPG was described in 1937 to measure blood volume changes. The technique is today increasingly used, in part because of developments in semiconductor technology during recent decades that have resulted in considerable advances in PPG probe design. Artificial neural networks help to detect complex nonlinear relationships and are extensively used in electronic signal analysis, including PPG. Patient and/or probe-tissue movement artifacts are sources of signal interference. Physiologic variations such as vasoconstriction, a deep gasp, or yawn also affect the signal. Monitoring respiratory rates from PPG are often based on respiratory-induced intensity variations (RIIVs) contained in the baseline of the PPG signal. Qualitative RIIV signals may be used for monitoring purposes regardless of age, gender, anesthesia, and mode of ventilation. Detection of breaths in adult volunteers had a maximal error of 8%, and in infants the rates of overdetected and missed breaths using PPG were 1.5% and 2.7%, respectively. During central apnea, the rhythmic RIIV signals caused by variations in intrathoracic pressure disappear. PPG has been evaluated for detecting airway obstruction with a sensitivity of 75% and a specificity of 85%. The RIIV and the pulse synchronous PPG waveform are sensitive for detecting hypovolemia. The respiratory synchronous variation of the PPG pulse amplitude is an accurate predictor of fluid responsiveness. Pleth variability index is a continuous measure of the

  2. VLSI signal processing technology

    CERN Document Server

    Swartzlander, Earl

    1994-01-01

    This book is the first in a set of forthcoming books focussed on state-of-the-art development in the VLSI Signal Processing area. It is a response to the tremendous research activities taking place in that field. These activities have been driven by two factors: the dramatic increase in demand for high speed signal processing, especially in consumer elec­ tronics, and the evolving microelectronic technologies. The available technology has always been one of the main factors in determining al­ gorithms, architectures, and design strategies to be followed. With every new technology, signal processing systems go through many changes in concepts, design methods, and implementation. The goal of this book is to introduce the reader to the main features of VLSI Signal Processing and the ongoing developments in this area. The focus of this book is on: • Current developments in Digital Signal Processing (DSP) pro­ cessors and architectures - several examples and case studies of existing DSP chips are discussed in...

  3. Vision Loss in Older Adults.

    Science.gov (United States)

    Pelletier, Allen L; Rojas-Roldan, Ledy; Coffin, Janis

    2016-08-01

    Vision loss affects 37 million Americans older than 50 years and one in four who are older than 80 years. The U.S. Preventive Services Task Force concludes that current evidence is insufficient to assess the balance of benefits and harms of screening for impaired visual acuity in adults older than 65 years. However, family physicians play a critical role in identifying persons who are at risk of vision loss, counseling patients, and referring patients for disease-specific treatment. The conditions that cause most cases of vision loss in older patients are age-related macular degeneration, glaucoma, ocular complications of diabetes mellitus, and age-related cataracts. Vitamin supplements can delay the progression of age-related macular degeneration. Intravitreal injection of a vascular endothelial growth factor inhibitor can preserve vision in the neovascular form of macular degeneration. Medicated eye drops reduce intraocular pressure and can delay the progression of vision loss in patients with glaucoma, but adherence to treatment is poor. Laser trabeculoplasty also lowers intraocular pressure and preserves vision in patients with primary open-angle glaucoma, but long-term studies are needed to identify who is most likely to benefit from surgery. Tight glycemic control in adults with diabetes slows the progression of diabetic retinopathy, but must be balanced against the risks of hypoglycemia and death in older adults. Fenofibrate also slows progression of diabetic retinopathy. Panretinal photocoagulation is the mainstay of treatment for diabetic retinopathy, whereas vascular endothelial growth factor inhibitors slow vision loss resulting from diabetic macular edema. Preoperative testing before cataract surgery does not improve outcomes and is not recommended.

  4. Unidirectional Cloaking Based on Metasurfaces with Balanced Loss and Gain

    Science.gov (United States)

    Sounas, Dimitrios L.; Fleury, Romain; Alù, Andrea

    2015-07-01

    We prove that balanced loss-gain distributions provide an elegant path towards realizing loss-free unidirectional cloaks for objects much larger than the wavelength. By coating a scatterer with an ultrathin metasurface with balanced loss and gain, such as a parity-time (P T )-symmetric metasurface in the special case of a symmetric scatterer, we show that it is possible to ideally cloak the scatterer from a particular direction. The passive portion of the cloak ensures that the incident power on the illuminated side of the object is fully absorbed, while the active portion radiates the required pattern on the opposite side, automatically synchronized with the impinging signal, eliminating shadows and making the object invisible. The proposed approach substitutes complex metamaterial cloaks and achieves cloaking with relaxed limitations on size, and in an ultrathin, loss-free, and stable design. Beyond introducing a new venue to cloaking of large objects, our paper shows the unique potential for scattering manipulation introduced by structures with balanced loss and gain, pointing to a new direction in the field of P T -symmetric systems.

  5. Impact of nonlinear loss on Stimulated Brillouin Scattering

    CERN Document Server

    Wolff, Christian; Steel, Michael J; Eggleton, Benjamin J; Poulton, Christopher G

    2015-01-01

    We study the impact of two-photon absorption (2PA) and fifth-order nonlinear loss such as 2PA-induced free-carrier absorption in semiconductors on the performance of Stimulated Brillouin Scattering devices. We formulate the equations of motion including effective loss coefficients, whose explicit expressions are provided for numerical evaluation in any waveguide geometry. We find that 2PA results in a monotonic, algebraic relationship between amplification, waveguide length and pump power, whereas fifth-order losses lead to a non-monotonic relationship. We define a figure of merit for materials and waveguide designs in the presence of fifth-order losses. From this, we determine the optimal waveguide length for the case of 2PA alone and upper bounds for the total Stokes amplification for the case of 2PA as well as fifth-order losses. The analysis is performed analytically using a small-signal approximation and is compared to numerical solutions of the full nonlinear modal equations.

  6. Comments on GUT monopole energy loss and ionization

    Energy Technology Data Exchange (ETDEWEB)

    Hagstrom, R.

    1982-01-01

    A few comments about the likely behavior of the electromagnetic energy loss and ionization rates of super-slowly moving magnetic monopoles are presented. The questions of energy loss rates and ionization rates for super-low monopoles passing through matter are considered, concentrating on aspects of these issues which affect practical detection techniques. It is worthwhile here to emphasize that there is a potentially great distinction between energy loss rates and ionization rates and that the magnitude of this distinction is really the great issue which must be settled in order to understand the significance of experimental results from present and proposed investigations of the slow monopole question. Energy loss here means the total dE/dX of the projectile due to interactions with the electrons of the slowing medium. To the extent that nuclear collisions can be neglected, this so-called electronic energy loss is the relevant quantity in questions about whether monopoles stop within the earth's crust, whether they are slowed by interstellar plasmas, or the signal in a truly calorimetric measurement (measuring temperature rises along the trajectory), etc. Most of our successful detection techniques depend upon the promotion of ground state electrons into states which lie above some energy gap in the material of the detector: electrons must be knocked completely free from the gas atoms in a proportional chamber gas, electrons must be promoted to a higher band in solid scintillator plastics. These processes are generically identified as ionization. (WHK)

  7. The Sound of Silence: Mouse Models for Hearing Loss

    Directory of Open Access Journals (Sweden)

    Sumantra Chatterjee

    2011-01-01

    Full Text Available Sensorineural hearing loss is one of the most common disabilities in humans. It is estimated that about 278 million people worldwide have slight to extreme hearing loss in both ears, which results in an economic loss for the country and personal loss for the individual. It is thus critical to have a deeper understanding of the causes for hearing loss to better manage and treat the affected individuals. The mouse serves as an excellent model to study and recapitulate some of these phenotypes, identify new genes which cause deafness, and to study their roles in vivo and in detail. Mutant mice have been instrumental in elucidating the function and mechanisms of the inner ear. The development and morphogenesis of the inner ear from an ectodermal layer into distinct auditory and vestibular components depends on well-coordinated gene expression and well-orchestrated signaling cascades within the otic vesicle and interactions with surrounding layers of tissues. Any disruption in these pathways can lead to hearing impairment. This review takes a look at some of the genes and their corresponding mice mutants that have shed light on the mechanism governing hearing impairment (HI in humans.

  8. Signal integrity characterization techniques

    CERN Document Server

    Bogatin, Eric

    2009-01-01

    "Signal Integrity Characterization Techniques" addresses the gap between traditional digital and microwave curricula all while focusing on a practical and intuitive understanding of signal integrity effects within the data transmission channel. High-speed interconnects such as connectors, PCBs, cables, IC packages, and backplanes are critical elements of differential channels that must be designed using today's most powerful analysis and characterization tools.Both measurements and simulation must be done on the device under test, and both activities must yield data that correlates with each other. Most of this book focuses on real-world applications of signal integrity measurements - from backplane for design challenges to error correction techniques to jitter measurement technologies. The authors' approach wisely addresses some of these new high-speed technologies, and it also provides valuable insight into its future direction and will teach the reader valuable lessons on the industry.

  9. Integrin signaling in atherosclerosis.

    Science.gov (United States)

    Finney, Alexandra C; Stokes, Karen Y; Pattillo, Christopher B; Orr, A Wayne

    2017-06-01

    Atherosclerosis, a chronic lipid-driven inflammatory disease affecting large arteries, represents the primary cause of cardiovascular disease in the world. The local remodeling of the vessel intima during atherosclerosis involves the modulation of vascular cell phenotype, alteration of cell migration and proliferation, and propagation of local extracellular matrix remodeling. All of these responses represent targets of the integrin family of cell adhesion receptors. As such, alterations in integrin signaling affect multiple aspects of atherosclerosis, from the earliest induction of inflammation to the development of advanced fibrotic plaques. Integrin signaling has been shown to regulate endothelial phenotype, facilitate leukocyte homing, affect leukocyte function, and drive smooth muscle fibroproliferative remodeling. In addition, integrin signaling in platelets contributes to the thrombotic complications that typically drive the clinical manifestation of cardiovascular disease. In this review, we examine the current literature on integrin regulation of atherosclerotic plaque development and the suitability of integrins as potential therapeutic targets to limit cardiovascular disease and its complications.

  10. Separation of Climate Signals

    Energy Technology Data Exchange (ETDEWEB)

    Kamath, C; Fodor, I

    2002-11-13

    Understanding changes in global climate is a challenging scientific problem. Simulated and observed data include signals from many sources, and untangling their respective effects is difficult. In order to make meaningful comparisons between different models, and to understand human effects on global climate, we need to isolate the effects of different sources. Recent eruptions of the El Chichon and Mt. Pinatubo volcanoes coincided with large El Nino and Southern Oscillation (ENSO) events, which complicates the separation of their contributions on global temperatures. Current approaches for separating volcano and ENSO signals in global mean data involve parametric models and iterative techniques [3]. We investigate alternative methods based on principal component analysis (PCA) [2] and independent component analysis (ICA) [1]. Our goal is to determine if such techniques can automatically identify the signals corresponding to the different sources, without relying on parametric models.

  11. Purinergic signalling and diabetes

    DEFF Research Database (Denmark)

    Burnstock, Geoffrey; Novak, Ivana

    2013-01-01

    signalling, we will focus on the role of purinergic signalling and its changes associated with diabetes in the pancreas and selected tissues/organ systems affected by hyperglycaemia and other stress molecules of diabetes. Since this is the first review of this kind, a comprehensive historical angle is taken......The pancreas is an organ with a central role in nutrient breakdown, nutrient sensing and release of hormones regulating whole body nutrient homeostasis. In diabetes mellitus, the balance is broken-cells can be starving in the midst of plenty. There are indications that the incidence of diabetes...... type 1 and 2, and possibly pancreatogenic diabetes, is rising globally. Events leading to insulin secretion and action are complex, but there is emerging evidence that intracellular nucleotides and nucleotides are not only important as intracellular energy molecules but also as extracellular signalling...

  12. PKD signaling and pancreatitis.

    Science.gov (United States)

    Yuan, Jingzhen; Pandol, Stephen J

    2016-07-01

    Acute pancreatitis is a serious medical disorder with no current therapies directed to the molecular pathogenesis of the disorder. Inflammation, inappropriate intracellular activation of digestive enzymes, and parenchymal acinar cell death by necrosis are the critical pathophysiologic processes of acute pancreatitis. Thus, it is necessary to elucidate the key molecular signals that mediate these pathobiologic processes and develop new therapeutic strategies to attenuate the appropriate signaling pathways in order to improve outcomes for this disease. A novel serine/threonine protein kinase D (PKD) family has emerged as key participants in signal transduction, and this family is increasingly being implicated in the regulation of multiple cellular functions and diseases. This review summarizes recent findings of our group and others regarding the signaling pathway and the biological roles of the PKD family in pancreatic acinar cells. In particular, we highlight our studies of the functions of PKD in several key pathobiologic processes associated with acute pancreatitis in experimental models. Our findings reveal that PKD signaling is required for NF-κB activation/inflammation, intracellular zymogen activation, and acinar cell necrosis in rodent experimental pancreatitis. Novel small-molecule PKD inhibitors attenuate the severity of pancreatitis in both in vitro and in vivo experimental models. Further, this review emphasizes our latest advances in the therapeutic application of PKD inhibitors to experimental pancreatitis after the initiation of pancreatitis. These novel findings suggest that PKD signaling is a necessary modulator in key initiating pathobiologic processes of pancreatitis, and that it constitutes a novel therapeutic target for treatments of this disorder.

  13. Notch signaling and ageing.

    Science.gov (United States)

    Polychronidou, Eleftheria; Vlachakis, Dimitrios; Vlamos, Panayiotis; Baumann, Marc; Kossida, Sophia

    2015-01-01

    Notch signaling is a master controller of the neural stem cell and neural development maintaining a significant role in the normal brain function. Notch genes are involved in embryogenesis, nervous system, and cardiovascular and endocrine function. On the other side, there are studies representing the involvement of Notch mutations in sporadic Alzheimer disease, other neurodegenerative diseases such as Down syndrome, Pick's and Prion's disease, and CADASIL. This manuscript attempts to present a holistic view of the positive or negative contribution of Notch signaling in the adult brain, and at the same time to present and promote the promising research fields of study.

  14. Understanding signal integrity

    CERN Document Server

    Thierauf, Stephen C

    2010-01-01

    This unique book provides you with practical guidance on understanding and interpreting signal integrity (SI) performance to help you with your challenging circuit board design projects. You find high-level discussions of important SI concepts presented in a clear and easily accessible format, including question and answer sections and bulleted lists.This valuable resource features rules of thumb and simple equations to help you make estimates of critical signal integrity parameters without using circuit simulators of CAD (computer-aided design). The book is supported with over 120 illustratio

  15. Electronic signal conditioning

    CERN Document Server

    NEWBY, BRUCE

    1994-01-01

    At technician level, brief references to signal conditioning crop up in a fragmented way in various textbooks, but there has been no single textbook, until now!More advanced texts do exist but they are more mathematical and presuppose a higher level of understanding of electronics and statistics. Electronic Signal Conditioning is designed for HNC/D students and City & Guilds Electronics Servicing 2240 Parts 2 & 3. It will also be useful for BTEC National, Advanced GNVQ, A-level electronics and introductory courses at degree level.

  16. Genomic signal processing

    CERN Document Server

    Shmulevich, Ilya

    2007-01-01

    Genomic signal processing (GSP) can be defined as the analysis, processing, and use of genomic signals to gain biological knowledge, and the translation of that knowledge into systems-based applications that can be used to diagnose and treat genetic diseases. Situated at the crossroads of engineering, biology, mathematics, statistics, and computer science, GSP requires the development of both nonlinear dynamical models that adequately represent genomic regulation, and diagnostic and therapeutic tools based on these models. This book facilitates these developments by providing rigorous mathema

  17. Physiological adaptations to weight loss and factors favouring weight regain.

    Science.gov (United States)

    Greenway, F L

    2015-08-01

    Obesity is a major global health problem and predisposes individuals to several comorbidities that can affect life expectancy. Interventions based on lifestyle modification (for example, improved diet and exercise) are integral components in the management of obesity. However, although weight loss can be achieved through dietary restriction and/or increased physical activity, over the long term many individuals regain weight. The aim of this article is to review the research into the processes and mechanisms that underpin weight regain after weight loss and comment on future strategies to address them. Maintenance of body weight is regulated by the interaction of a number of processes, encompassing homoeostatic, environmental and behavioural factors. In homoeostatic regulation, the hypothalamus has a central role in integrating signals regarding food intake, energy balance and body weight, while an 'obesogenic' environment and behavioural patterns exert effects on the amount and type of food intake and physical activity. The roles of other environmental factors are also now being considered, including sleep debt and iatrogenic effects of medications, many of which warrant further investigation. Unfortunately, physiological adaptations to weight loss favour weight regain. These changes include perturbations in the levels of circulating appetite-related hormones and energy homoeostasis, in addition to alterations in nutrient metabolism and subjective appetite. To maintain weight loss, individuals must adhere to behaviours that counteract physiological adaptations and other factors favouring weight regain. It is difficult to overcome physiology with behaviour. Weight loss medications and surgery change the physiology of body weight regulation and are the best chance for long-term success. An increased understanding of the physiology of weight loss and regain will underpin the development of future strategies to support overweight and obese individuals in their efforts

  18. Physiological adaptations to weight loss and factors favouring weight regain

    Science.gov (United States)

    Greenway, F L

    2015-01-01

    Obesity is a major global health problem and predisposes individuals to several comorbidities that can affect life expectancy. Interventions based on lifestyle modification (for example, improved diet and exercise) are integral components in the management of obesity. However, although weight loss can be achieved through dietary restriction and/or increased physical activity, over the long term many individuals regain weight. The aim of this article is to review the research into the processes and mechanisms that underpin weight regain after weight loss and comment on future strategies to address them. Maintenance of body weight is regulated by the interaction of a number of processes, encompassing homoeostatic, environmental and behavioural factors. In homoeostatic regulation, the hypothalamus has a central role in integrating signals regarding food intake, energy balance and body weight, while an ‘obesogenic' environment and behavioural patterns exert effects on the amount and type of food intake and physical activity. The roles of other environmental factors are also now being considered, including sleep debt and iatrogenic effects of medications, many of which warrant further investigation. Unfortunately, physiological adaptations to weight loss favour weight regain. These changes include perturbations in the levels of circulating appetite-related hormones and energy homoeostasis, in addition to alterations in nutrient metabolism and subjective appetite. To maintain weight loss, individuals must adhere to behaviours that counteract physiological adaptations and other factors favouring weight regain. It is difficult to overcome physiology with behaviour. Weight loss medications and surgery change the physiology of body weight regulation and are the best chance for long-term success. An increased understanding of the physiology of weight loss and regain will underpin the development of future strategies to support overweight and obese individuals in their

  19. Temporary Losses of Highway Capacity and Impacts on Performance

    Energy Technology Data Exchange (ETDEWEB)

    Chin, S.M.

    2002-07-31

    Traffic congestion and its impacts significantly affect the nation's economic performance and the public's quality of life. In most urban areas, travel demand routinely exceeds highway capacity during peak periods. In addition, events such as crashes, vehicle breakdowns, work zones, adverse weather, and suboptimal signal timing cause temporary capacity losses, often worsening the conditions on already congested highway networks. The impacts of these temporary capacity losses include delay, reduced mobility, and reduced reliability of the highway system. They can also cause drivers to re-route or reschedule trips. Prior to this study, no nationwide estimates of temporary losses of highway capacity had been made by type of capacity-reducing event. Such information is vital to formulating sound public policies for the highway infrastructure and its operation. This study is an initial attempt to provide nationwide estimates of the capacity losses and delay caused by temporary capacity-reducing events. The objective of this study was to develop and implement methods for producing national-level estimates of the loss of capacity on the nation's highway facilities due to temporary phenomena as well as estimates of the impacts of such losses. The estimates produced by this study roughly indicate the magnitude of problems that are likely be addressed by the Congress during the next re-authorization of the Surface Transportation Programs. The scope of the study includes all urban and rural freeways and principal arterials in the nation's highway system for 1999. Specifically, this study attempts to quantify the extent of temporary capacity losses due to crashes, breakdowns, work zones, weather, and sub-optimal signal timing. These events can cause impacts such as capacity reduction, delays, trip rescheduling, rerouting, reduced mobility, and reduced reliability. This study focuses on the reduction of capacity and resulting delays caused by the temporary

  20. RF Path and Absorption Loss Estimation for Underwater Wireless Sensor Networks in Different Water Environments.

    Science.gov (United States)

    Qureshi, Umair Mujtaba; Shaikh, Faisal Karim; Aziz, Zuneera; Shah, Syed M Zafi S; Sheikh, Adil A; Felemban, Emad; Qaisar, Saad Bin

    2016-06-16

    Underwater Wireless Sensor Network (UWSN) communication at high frequencies is extremely challenging. The intricacies presented by the underwater environment are far more compared to the terrestrial environment. The prime reason for such intricacies are the physical characteristics of the underwater environment that have a big impact on electromagnetic (EM) signals. Acoustics signals are by far the most preferred choice for underwater wireless communication. Because high frequency signals have the luxury of large bandwidth (BW) at shorter distances, high frequency EM signals cannot penetrate and propagate deep in underwater environments. The EM properties of water tend to resist their propagation and cause severe attenuation. Accordingly, there are two questions that need to be addressed for underwater environment, first what happens when high frequency EM signals operating at 2.4 GHz are used for communication, and second which factors affect the most to high frequency EM signals. To answer these questions, we present real-time experiments conducted at 2.4 GHz in terrestrial and underwater (fresh water) environments. The obtained results helped in studying the physical characteristics (i.e., EM properties, propagation and absorption loss) of underwater environments. It is observed that high frequency EM signals can propagate in fresh water at a shallow depth only and can be considered for a specific class of applications such as water sports. Furthermore, path loss, velocity of propagation, absorption loss and the rate of signal loss in different underwater environments are also calculated and presented in order to understand why EM signals cannot propagate in sea water and oceanic water environments. An optimal solk6ution for underwater communication in terms of coverage distance, bandwidth and nature of communication is presented, along with possible underwater applications of UWSNs at 2.4 GHz.

  1. RF Path and Absorption Loss Estimation for Underwater Wireless Sensor Networks in Different Water Environments

    Directory of Open Access Journals (Sweden)

    Umair Mujtaba Qureshi

    2016-06-01

    Full Text Available Underwater Wireless Sensor Network (UWSN communication at high frequencies is extremely challenging. The intricacies presented by the underwater environment are far more compared to the terrestrial environment. The prime reason for such intricacies are the physical characteristics of the underwater environment that have a big impact on electromagnetic (EM signals. Acoustics signals are by far the most preferred choice for underwater wireless communication. Because high frequency signals have the luxury of large bandwidth (BW at shorter distances, high frequency EM signals cannot penetrate and propagate deep in underwater environments. The EM properties of water tend to resist their propagation and cause severe attenuation. Accordingly, there are two questions that need to be addressed for underwater environment, first what happens when high frequency EM signals operating at 2.4 GHz are used for communication, and second which factors affect the most to high frequency EM signals. To answer these questions, we present real-time experiments conducted at 2.4 GHz in terrestrial and underwater (fresh water environments. The obtained results helped in studying the physical characteristics (i.e., EM properties, propagation and absorption loss of underwater environments. It is observed that high frequency EM signals can propagate in fresh water at a shallow depth only and can be considered for a specific class of applications such as water sports. Furthermore, path loss, velocity of propagation, absorption loss and the rate of signal loss in different underwater environments are also calculated and presented in order to understand why EM signals cannot propagate in sea water and oceanic water environments. An optimal solk6ution for underwater communication in terms of coverage distance, bandwidth and nature of communication is presented, along with possible underwater applications of UWSNs at 2.4 GHz.

  2. LPA receptor signaling: pharmacology, physiology, and pathophysiology.

    Science.gov (United States)

    Yung, Yun C; Stoddard, Nicole C; Chun, Jerold

    2014-07-01

    Lysophosphatidic acid (LPA) is a small ubiquitous lipid found in vertebrate and nonvertebrate organisms that mediates diverse biological actions and demonstrates medicinal relevance. LPA's functional roles are driven by extracellular signaling through at least six 7-transmembrane G protein-coupled receptors. These receptors are named LPA1-6 and signal through numerous effector pathways activated by heterotrimeric G proteins, including Gi/o, G12/13, Gq, and Gs LPA receptor-mediated effects have been described in numerous cell types and model systems, both in vitro and in vivo, through gain- and loss-of-function studies. These studies have revealed physiological and pathophysiological influences on virtually every organ system and developmental stage of an organism. These include the nervous, cardiovascular, reproductive, and pulmonary systems. Disturbances in normal LPA signaling may contribute to a range of diseases, including neurodevelopmental and neuropsychiatric disorders, pain, cardiovascular disease, bone disorders, fibrosis, cancer, infertility, and obesity. These studies underscore the potential of LPA receptor subtypes and related signaling mechanisms to provide novel therapeutic targets. Copyright © 2014 by the American Society for Biochemistry and Molecular Biology, Inc.

  3. Beam Loss and Residual Activation Trending

    CERN Document Server

    Dodson, George W; Ruffin, Ariel T; Williams, Theodore L

    2005-01-01

    The SNS Front End, Drift Tube Linac and most of the Coupled Cavity Linac have been operated during commissioning. Beam loss data were taken with differential Beam Current Monitors, and Beam loss Monitors during commissioning. Residual activation data were taken at various times during and after the run. An analysis of beam loss trending, beam loss monitor data and residual activation will be shown.

  4. 7 CFR 1437.301 - Value loss.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Value loss. 1437.301 Section 1437.301 Agriculture... Coverage Using Value § 1437.301 Value loss. (a) Special provisions are required to assess losses and calculate assistance for a few crops and commodities which do not lend themselves to yield loss situations...

  5. 38 CFR 4.40 - Functional loss.

    Science.gov (United States)

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false Functional loss. 4.40... DISABILITIES Disability Ratings The Musculoskeletal System § 4.40 Functional loss. Disability of the... damage, and the functional loss, with respect to all these elements. The functional loss may be due to...

  6. Coping with Your Loss and Grief.

    Science.gov (United States)

    Oregon State Univ., Corvallis. Cooperative Extension Service.

    This guide offers advice to help people cope with a variety of losses, including losses associated with divorce, retirement, relocation, disability, or illness, and the loss of a pet, financial security, independence, or control and decision making. It discusses what one can expect when one suffers a loss and how to handle grief. Common reactions…

  7. 10 Ways to Identify Hearing Loss

    Science.gov (United States)

    ... of this page please turn JavaScript on. Feature: Hearing Loss 10 Ways to Identify Hearing Loss Past Issues / Spring 2015 Table of Contents If ... gov Internet: www.nidcd.nih.gov Read More "Hearing Loss" Articles Managing Hearing Loss / Symptoms, Devices, Prevention & Research / ...

  8. Prohibitions against Mourning in Childhood Sibling Loss.

    Science.gov (United States)

    Rosen, Helen

    1985-01-01

    Presents findings from a research study on sibling loss in childhood which support the idea that the loss of a sibling in childhood may be an especially significant loss for a child, in that both internal, family, and societal influences prohibit the opportunity to mourn the loss. (Author/NRB)

  9. A comparison of nonlinear media for parametric all-optical signal processing

    DEFF Research Database (Denmark)

    Martinez Diaz, Jordi; Bohigas Nadal, Jaume; Vukovic, Dragana

    2013-01-01

    We systematically compare nonlinear media for parametric signal processing by determining the minimum pump power that is required for a given conversion efficiency in a degenerate four-wave mixing process, including the effect of nonlinear loss.......We systematically compare nonlinear media for parametric signal processing by determining the minimum pump power that is required for a given conversion efficiency in a degenerate four-wave mixing process, including the effect of nonlinear loss....

  10. Frequency dependence of the pump-to-signal RIN transfer in fiber optical parametric amplifiers

    DEFF Research Database (Denmark)

    Pakarzadeh Dezfuli Nezhad, Hassan; Rottwitt, Karsten; Zakery, A.

    2009-01-01

    Using a numerical model, the frequency dependence of the pump-to-signal RIN transfer in FOPAs has been investigated. The model includes fiber loss, pump depletion as well as difference in group velocity among interacting beams.......Using a numerical model, the frequency dependence of the pump-to-signal RIN transfer in FOPAs has been investigated. The model includes fiber loss, pump depletion as well as difference in group velocity among interacting beams....

  11. Methadone Induced Sensorineural Hearing Loss

    Directory of Open Access Journals (Sweden)

    Chadi Saifan

    2013-01-01

    Full Text Available Background. Sudden sensorineural hearing loss (SSHL caused by opiate abuse or overuse has been well documented in the medical literature. Most documented case reports have involved either heroin or hydrocodone/acetaminophen. Recently, case reposts of methadone induced SSHL have been published. Case Report. We present the case of a 31-year-old man who developed SSHL after a methadone overdose induced stupor. He was subsequently restarted on methadone at his regular dose. On follow-up audiometry exams, he displayed persistent moderately severe sensorineural hearing loss bilaterally. Discussion. This case is notable because unlike all but one previously reported case, the patient—who was restated on methadone—did not make a complete recovery. Conclusion. Methadone overuse in rare cases causes SSHL.

  12. Visual loss after orthopedic procedures.

    Science.gov (United States)

    Kaeser, Pierre-François; Borruat, François-Xavier

    2011-02-01

    Perioperative visual loss (PVL) is a very rare and unpredictable complication of surgery performed at distance from the visual pathways, mostly after spine or cardiac procedures. We report 6 consecutive patients with PVL after routine orthopedic procedures (osteosynthesis for complex fracture of the femur [2], total hip arthroplasty [2], hip prosthesis arthroplasty [1], bilateral simultaneous total knee arthroplasty [1]) and reviewed the literature on the subject. An ischemic optic neuropathy was diagnosed in all cases, and visual loss was bilateral in 5 of 6 patients. Partial visual improvement occurred in only 3 of 11 eyes. No specific therapy is available for PVL. Postoperative visual disturbances should prompt without delay an ophthalmic evaluation because emergent correction of anemia, systemic hypotension, or hypovolemia might improve visual prognosis of PVL. Copyright © 2011 Elsevier Inc. All rights reserved.

  13. Noise exposure and hearing loss

    Energy Technology Data Exchange (ETDEWEB)

    Tempest, W.

    1978-03-01

    Current standards for occupational noise exposure are discussed briefly. Previously published data from two major surveys are used to derive noise-induced hearing loss audiograms for workers of average, and above average, sensitivity who have spent a working life of 40 yr exposed to noise at the maximum levels currently recommended; estimates of the percentage risk of hearing loss are quoted. A number of individual cases, in which claimants have been exposed to noise levels close to the current criteria, are described. It is concluded that the standards currently in use do not provide anything like complete protection especially to the more sensitive workers, and may leave employers open to common law actions for damages.

  14. Recurrent pregnancy loss and obesity.

    Science.gov (United States)

    Sugiura-Ogasawara, Mayumi

    2015-05-01

    Recurrent pregnancy loss (RPL) was defined as two or more miscarriages. Antiphospholipid syndrome, uterine anomalies, and parental chromosomal abnormalities, particularly translocation and abnormal embryonic karyotype, are identifiable causes of RPL. Obesity may increase the risk of sporadic miscarriage in pregnancies conceived spontaneously. Obesity with body mass index (BMI)>30 kg/m2 is an independent risk factor for further miscarriage with odds ratio 1.7-3.5 in patients with early RPL. Obesity is associated with euploid miscarriage. Unexplained RPL with euploid embryo might be a common disease caused by both polymorphisms of multiple susceptibility genes and lifestyle factors such as women's age, obesity, and smoking. Patients with a history of RPL were found to have a higher risk of cardiovascular disease, celiac disease, gastric ulcer, gastritis, and atopic dermatitis. No study has examined the effect of weight loss on the prevention of further miscarriage in patients with RPL. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Toxicity of weight loss agents.

    Science.gov (United States)

    Yen, May; Ewald, Michele Burns

    2012-06-01

    With the rise of the obesity epidemic in the United States over the last several decades and the medical complications seen with it, weight loss and dieting have become a national public health concern. Because of their increased use and availability through internet sales, several different dieting agents were reviewed for potential toxicity. These included: syrup of ipecac, cathartics, human chorionic gonadotropin hormone, 2,4 Dinitrophenol, guar gum, phenylpropanolamine, ma huang/ ephedra, caffeine, clenbuterol, fenfluramine, sibutramine, thyroid hormone, orlistat and cannabinoid antagonists. With the internet making even banned products readily accessible, healthcare providers need to be aware of the potential toxicities of a wide range of weight loss agents. Our review covered topics we thought to be most historically significant as well as pertinent to the practice of medical toxicology today.

  16. FTO genotype and weight loss

    DEFF Research Database (Denmark)

    Livingstone, Katherine M; Celis-Morales, Carlos; Papandonatos, George D

    2016-01-01

    : Ovid Medline, Scopus, Embase, and Cochrane from inception to November 2015. ELIGIBILITY CRITERIA FOR STUDY SELECTION: Randomised controlled trials in overweight or obese adults reporting reduction in body mass index, body weight, or waist circumference by FTO genotype (rs9939609 or a proxy) after...... well to dietary, physical activity, or drug based weight loss interventions and thus genetic predisposition to obesity associated with the FTO minor allele can be at least partly counteracted through such interventions. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42015015969.......OBJECTIVE: To assess the effect of the FTO genotype on weight loss after dietary, physical activity, or drug based interventions in randomised controlled trials. DESIGN: Systematic review and random effects meta-analysis of individual participant data from randomised controlled trials. DATA SOURCES...

  17. Analog signal isolation techniques

    Energy Technology Data Exchange (ETDEWEB)

    Beadle, E.R.

    1992-12-31

    This paper discusses several techniques for isolating analog signals in an accelerator environment. The techniques presented here encompass isolation amplifiers, voltage-to-frequency converters (VIFCs), transformers, optocouplers, discrete fiber optics, and commercial fiber optic links. Included within the presentation of each method are the design issues that must be considered when selecting the isolation method for a specific application.

  18. Analog signal isolation techniques

    Energy Technology Data Exchange (ETDEWEB)

    Beadle, E.R.

    1992-01-01

    This paper discusses several techniques for isolating analog signals in an accelerator environment. The techniques presented here encompass isolation amplifiers, voltage-to-frequency converters (VIFCs), transformers, optocouplers, discrete fiber optics, and commercial fiber optic links. Included within the presentation of each method are the design issues that must be considered when selecting the isolation method for a specific application.

  19. Drought Signaling in Plants

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 4; Issue 6. Drought Signaling in Plants. G Sivakumar Swamy. General Article Volume 4 Issue 6 June 1999 pp 34-44. Fulltext. Click here to view fulltext PDF. Permanent link: http://www.ias.ac.in/article/fulltext/reso/004/06/0034-0044. Author Affiliations.

  20. Symposium: Unveiling Affective Signals

    NARCIS (Netherlands)

    van den Broek, Egon; Nijholt, Antinus; Westerink, J.H.D.M.; Spink, A.J.; Grieco, F; Krips, O.E.; Loijens, L.W.S.; Noldus, L.P.J.J.; Zimmerman, P.H.

    2010-01-01

    The ability to process and, subsequently, understand affective signals is the core of emotional intelligence and empathy. However, more than a decade of research in affective computing has shown that it is hard to develop computational models of this process. We pose that the solution for this

  1. Unveiling Affective Signals

    NARCIS (Netherlands)

    van den Broek, Egon; Nijholt, Antinus; Westerink, J.H.D.M.; Barakova, E.; de Ruyter, B.; Spink, A

    2010-01-01

    The ability to process and, subsequently, understand affective signals is the core of emotional intelligence and empathy. However, more than a decade of research in affective computing has shown that it is hard to develop computational models of this process. We pose that the solution for this

  2. Selenium and redox signaling.

    Science.gov (United States)

    Brigelius-Flohé, Regina; Flohé, Leopold

    2017-03-01

    Selenium compounds that contain selenol functions or can be metabolized to selenols are toxic via superoxide and H2O2 generation, when ingested at dosages beyond requirement. At supra-nutritional dosages various forms of programmed cell death are observed. At physiological intakes, selenium exerts its function as constituent of selenoproteins, which overwhelmingly are oxidoreductases. Out of those, the glutathione peroxidases counteract hydroperoxide-stimulated signaling cascades comprising inflammation triggered by cytokines or lipid mediators, insulin signaling and different forms of programmed cell death. Similar events are exerted by peroxiredoxins, which functionally depend on the selenoproteins of the thioredoxin reductase family. The thiol peroxidases of both families can, however, also act as sensors for hydroperoxides, thereby initiating signaling cascades. Although the interaction of selenoproteins with signaling events has been established by genetic techniques, the in vivo relevance of these findings is still hard to delineate for several reasons: The biosynthesis of individual selenoproteins responds differently to variations of selenium intakes; selenium is preferentially delivered to privileged tissues via inter-organ trafficking and receptor-mediated uptake, and only half of the selenoproteins known by sequence have been functionally characterized. The fragmentary insights do not allow any uncritical use of selenium for optimizing human health. Copyright © 2016. Published by Elsevier Inc.

  3. Satiety signals and obesity.

    Science.gov (United States)

    Hellström, Per M

    2013-03-01

    The obesity epidemic over the world has called to attention different ways to manage this development. As bariatric surgery today is the only manner by which rapid and sustained weight control can be achieved, new ways of treating obesity are under investigation. This review focuses on today's knowledge on satiety signaling as a means to combat obesity. The combined knowledge achieved from obesity surgery with gastric bypass and duodenal switch together with the pharmacological treatment of type 2 diabetes have given us some clues of how to manage obesity. The basis for our understanding is the present research focusing on the gut peptide hormones that are released in response to food intake, and the paucity of satiety signaling seems to prevail in obesity. This means that obese patients experience less activation of higher brain centers in association with a meal and therefore compensate with increased meal size or frequent food intake. Altered satiety signaling primarily emanating from the gastrointestinal tract seems to lead to the development of obesity and type 2 diabetes. Pharmacological tools that enhance the gut hormone signaling are in focus for the upcoming venues of treatment.

  4. Signalling Nouns in Discourse.

    Science.gov (United States)

    Flowerdew, John

    2003-01-01

    Presents a description of a major class of vocabulary, signalling nouns, that have important discourse functions in establishing links across and within clauses. The description provides a framework useful to materials writers, teachers, and learners of English for academic purposes. (Author/VWL)

  5. Sangaste loss / Otto Pius Hippius

    Index Scriptorium Estoniae

    Hippius, Otto Pius, 1826-1883

    1996-01-01

    esmakordselt mainitud 13. saj. Sangaste mõisa omanik Berg, Friedrich Wilhelm (1794-1874). Lossi interjöörid, fotod 1920-ndatest aastatest, lossi välisvaade, foto 1920-ndatest aastatest, lk. 335. Loss, vaade esifassaadile, värv., lk. 336-337, Vaade lossile üle tiigi metsapargist, värv., lk. 338. Ballisaal, salong, värv.

  6. Loss and damage livelihood resilience

    OpenAIRE

    Geest, Kees van der; Kreft, Sönke; Zommers, Zinta; Huq, Saleemul; Quandt, Amy; Preato, Alberto; Chandra, Alvin; Mulla, Ava; Chaffin, Brian; Koto, Camari; Barthelt, Christian; Carter, Christopher J.; Corendea, Cosmin; Wrathall, David; Opondo, Denis Opiyo

    2016-01-01

    Climate change Loss and Damage has emerged as a key challenge of the 21st century. This Policy Brief first frames the challenge and then introduces the Resilience Academy, highlighting 5 key insights that both feed the debate and inform action. Finally, it provides 5 recommendations to the Executive Committee of the Warsaw International Mechanism (WIM ExCom) for its 5-year work plan.

  7. Noise-induced hearing loss

    OpenAIRE

    Mariola Sliwinska-Kowalska; Adrian Davis

    2012-01-01

    Noise-induced hearing loss (NIHL) still remains a problem in developed countries, despite reduced occupational noise exposure, strict standards for hearing protection and extensive public health awareness campaigns. Therefore NIHL continues to be the focus of noise research activities. This paper summarizes progress achieved recently in our knowledge of NIHL. It includes papers published between the years 2008-2011 (in English), which were identified by a literature search of accessible medic...

  8. Gastric stimulation for weight loss

    Science.gov (United States)

    Mizrahi, Meir; Ben Ya'acov, Ami; Ilan, Yaron

    2012-01-01

    The prevalence of obesity is growing to epidemic proportions, and there is clearly a need for minimally invasive therapies with few adverse effects that allow for sustained weight loss. Behavior and lifestyle therapy are safe treatments for obesity in the short term, but the durability of the weight loss is limited. Although promising obesity drugs are in development, the currently available drugs lack efficacy or have unacceptable side effects. Surgery leads to long-term weight loss, but it is associated with morbidity and mortality. Gastric electrical stimulation (GES) has received increasing attention as a potential tool for treating obesity and gastrointestinal dysmotility disorders. GES is a promising, minimally invasive, safe, and effective method for treating obesity. External gastric pacing is aimed at alteration of the motility of the gastrointestinal tract in a way that will alter absorption due to alteration of transit time. In addition, data from animal models and preliminary data from human trials suggest a role for the gut-brain axis in the mechanism of GES. This may involve alteration of secretion of hormones associated with hunger or satiety. Patient selection for gastric stimulation therapy seems to be an important determinant of the treatment’s outcome. Here, we review the current status, potential mechanisms of action, and possible future applications of gastric stimulation for obesity. PMID:22654422

  9. Mutation analysis of suppressor of cytokine signalling 3, a candidate gene in Type 1 diabetes and insulin sensitivity

    DEFF Research Database (Denmark)

    Gylvin, T; Nolsøe, R; Hansen, T

    2004-01-01

    Beta cell loss in Type 1 and Type 2 diabetes mellitus may result from apoptosis and necrosis induced by inflammatory mediators. The suppressor of cytokine signalling (SOCS)-3 is a natural inhibitor of cytokine signalling and also influences insulin signalling. SOCS3 could therefore be a candidate...

  10. Small Turing universal signal machines

    Directory of Open Access Journals (Sweden)

    Jérôme Durand-Lose

    2009-06-01

    Full Text Available This article aims at providing signal machines as small as possible able to perform any computation (in the classical understanding. After presenting signal machines, it is shown how to get universal ones from Turing machines, cellular-automata and cyclic tag systems. Finally a halting universal signal machine with 13 meta-signals and 21 collision rules is presented.

  11. Critical nodes in signalling pathways

    DEFF Research Database (Denmark)

    Taniguchi, Cullen M; Emanuelli, Brice; Kahn, C Ronald

    2006-01-01

    Physiologically important cell-signalling networks are complex, and contain several points of regulation, signal divergence and crosstalk with other signalling cascades. Here, we use the concept of 'critical nodes' to define the important junctions in these pathways and illustrate their unique role...... using insulin signalling as a model system....

  12. Cryogenic Semiconductor Detectors: Simulation of Signal Formation & Irradiation Beam Test

    CERN Document Server

    AUTHOR|(CDS)2091318; Stamoulis, G; Vavougios, D

    The Beam Loss Monitoring system of the Large Hadron Collider is responsible for the pro- tection of the machine from damage and for the prevention of a magnet quench. Near the interaction points of the LHC, in the triplet magnets area, the BLMs are sensitive to the collision debris, limiting their ability to distinguish beam loss signal from signal caused due to the collision products. Placing silicon & diamond detectors inside the cold mass of the mag- nets, in liquid helium temperatures, would provide significant improvement to the precision of the measurement of the energy deposition in the superconducting coil of the magnet. To further study the signal formation and the shape of the transient current pulses of the aforementioned detectors in cryogenic temperatures, a simulation application has been developed. The application provides a fast way of determining the electric field components inside the detectors bulk and then introduces an initial charge distribution based on the properties of the radiat...

  13. Bending loss of terahertz pipe waveguides.

    Science.gov (United States)

    Lu, Jen-Tang; Hsueh, Yu-Chun; Huang, Yu-Ru; Hwang, Yuh-Jing; Sun, Chi-Kuang

    2010-12-06

    We present an experimental study on the bending loss of terahertz (THz) pipe waveguide. Bending loss of pipe waveguides is investigated for various frequencies, polarizations, core diameters, cladding thicknesses, and cladding materials. Our results indicate that the pipe waveguides with lower guiding loss suffer lower bending loss due to stronger mode confinement. The unexpected low bending loss in the investigated simple leaky waveguide structure promises variety of flexible applications.

  14. Multiresolution Analysis of EEG Signals

    OpenAIRE

    Borowska Marta; Białobłocka Natalia

    2016-01-01

    This paper reports on a multiresolution analysis of EEG signals. The dominant frequency components of signals with and without observed epileptic discharges were compared. The study showed that there were significant differences in dominant frequency between the signals with epileptic discharges and the signals without discharges. This gives the ability to identify epilepsy during EEG examination. The frequency of the signals coming from the frontal, central, parietal and occipital channels a...

  15. Loss of CSL Unlocks a Hypoxic Response and Enhanced Tumor Growth Potential in Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Eike-Benjamin Braune

    2016-05-01

    Full Text Available Notch signaling is an important regulator of stem cell differentiation. All canonical Notch signaling is transmitted through the DNA-binding protein CSL, and hyperactivated Notch signaling is associated with tumor development; thus it may be anticipated that CSL deficiency should reduce tumor growth. In contrast, we report that genetic removal of CSL in breast tumor cells caused accelerated growth of xenografted tumors. Loss of CSL unleashed a hypoxic response during normoxic conditions, manifested by stabilization of the HIF1α protein and acquisition of a polyploid giant-cell, cancer stem cell-like, phenotype. At the transcriptome level, loss of CSL upregulated more than 1,750 genes and less than 3% of those genes were part of the Notch transcriptional signature. Collectively, this suggests that CSL exerts functions beyond serving as the central node in the Notch signaling cascade and reveals a role for CSL in tumorigenesis and regulation of the cellular hypoxic response.

  16. Vision loss and hearing loss in painting and musical composition.

    Science.gov (United States)

    Marmor, Michael F

    2014-07-01

    This article considers the impact of vision and hearing loss on great painters and musical composers. The visual work of Mary Cassatt, Georgia O'Keeffe, Edgar Degas, and Claude Monet all showed alterations as their vision failed. In contrast, Gabriel Fauré, Bedřich Smetana, and Ludwig von Beethoven wrote many of their best compositions while totally deaf, and Georg Friedrich Handel and Frederick Delius struggled to compose late in life when they lost their vision (although their hearing remained excellent). There are 2 major distinctions between the role of vision and hearing for these artistic disciplines. First, there is a surrogate means of "hearing" music, through the musical score, which allows composers to write and edit music while totally deaf. The greatest problem with deafness for a skilled composer is interference from internal noise (tinnitus). There is no surrogate for vision to allow a painter to work when the subject is a blur or the colors on the canvas cannot be distinguished. Second, although the appreciation of art is visual and that of music is auditory, the transcription of both art and musical composition is visual. Thus, visual loss does pose a problem for a composer accustomed to working with good sight, because it disrupts habitual methods of writing and editing music. Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

  17. Increased ERK signalling promotes inflammatory signalling in primary airway epithelial cells expressing Z α1-antitrypsin.

    Science.gov (United States)

    van 't Wout, Emily F A; Dickens, Jennifer A; van Schadewijk, Annemarie; Haq, Imran; Kwok, Hang Fai; Ordóñez, Adriana; Murphy, Gillian; Stolk, Jan; Lomas, David A; Hiemstra, Pieter S; Marciniak, Stefan J

    2014-02-15

    Overexpression of Z α1-antitrypsin is known to induce polymer formation, prime the cells for endoplasmic reticulum stress and initiate nuclear factor kappa B (NF-κB) signalling. However, whether endogenous expression in primary bronchial epithelial cells has similar consequences remains unclear. Moreover, the mechanism of NF-κB activation has not yet been elucidated. Here, we report excessive NF-κB signalling in resting primary bronchial epithelial cells from ZZ patients compared with wild-type (MM) controls, and this appears to be mediated by mitogen-activated protein/extracellular signal-regulated kinase, EGF receptor and ADAM17 activity. Moreover, we show that rather than being a response to protein polymers, NF-κB signalling in airway-derived cells represents a loss of anti-inflammatory signalling by M α1-antitrypsin. Treatment of ZZ primary bronchial epithelial cells with purified plasma M α1-antitrypsin attenuates this inflammatory response, opening up new therapeutic options to modulate airway inflammation in the lung.

  18. Signals and Responses

    Science.gov (United States)

    Lee, Angie

    2006-01-01

    The nitrogen-fixing symbiosis between bacteria in the family Rhizobiaceae and members of the legume family (Fabaceae) has been well studied, particularly from the perspective of the early signaling and recognition events. Recent studies of non-nodulating legume mutants have resulted in the identification of a number of genes that are responsive to signal molecules from the bacteria. However, a second group of nodule-forming bacteria, completely unrelated to the Rhizobiaceae, which are α-Proteobacteria, has been discovered. These bacteria belong to the β-Proteobacteria and have been designated β-rhizobia to distinguish them from the better-known α-rhizobia. Here, we review what is known in this economically important symbiosis about the interaction between legumes and α-rhizobia, and we incorporate information, where known, about the β-rhizobia. PMID:19521481

  19. Biomedical signal analysis

    CERN Document Server

    Rangayyan, Rangaraj M

    2015-01-01

    The book will help assist a reader in the development of techniques for analysis of biomedical signals and computer aided diagnoses with a pedagogical examination of basic and advanced topics accompanied by over 350 figures and illustrations. Wide range of filtering techniques presented to address various applications. 800 mathematical expressions and equations. Practical questions, problems and laboratory exercises. Includes fractals and chaos theory with biomedical applications.

  20. Noise-induced hearing loss

    Directory of Open Access Journals (Sweden)

    Mariola Sliwinska-Kowalska

    2012-01-01

    Full Text Available Noise-induced hearing loss (NIHL still remains a problem in developed countries, despite reduced occupational noise exposure, strict standards for hearing protection and extensive public health awareness campaigns. Therefore NIHL continues to be the focus of noise research activities. This paper summarizes progress achieved recently in our knowledge of NIHL. It includes papers published between the years 2008-2011 (in English, which were identified by a literature search of accessible medical and other relevant databases. A substantial part of this research has been concerned with the risk of NIHL in the entertainment sector, particularly in professional, orchestral musicians. There are also constant concerns regarding noise exposure and hearing risk in "hard to control" occupations, such as farming and construction work. Although occupational noise has decreased since the early 1980s, the number of young people subject to social noise exposure has tripled. If the exposure limits from the Noise at Work Regulations are applied, discotheque music, rock concerts, as well as music from personal music players are associated with the risk of hearing loss in teenagers and young adults. Several recent research studies have increased the understanding of the pathomechanisms of acoustic trauma, the genetics of NIHL, as well as possible dietary and pharmacologic otoprotection in acoustic trauma. The results of these studies are very promising and offer grounds to expect that targeted therapies might help prevent the loss of sensory hair cells and protect the hearing of noise-exposed individuals. These studies emphasize the need to launch an improved noise exposure policy for hearing protection along with developing more efficient norms of NIHL risk assessment.

  1. Noise-induced hearing loss.

    Science.gov (United States)

    Sliwinska-Kowalska, Mariola; Davis, Adrian

    2012-01-01

    Noise-induced hearing loss (NIHL) still remains a problem in developed countries, despite reduced occupational noise exposure, strict standards for hearing protection and extensive public health awareness campaigns. Therefore NIHL continues to be the focus of noise research activities. This paper summarizes progress achieved recently in our knowledge of NIHL. It includes papers published between the years 2008-2011 (in English), which were identified by a literature search of accessible medical and other relevant databases. A substantial part of this research has been concerned with the risk of NIHL in the entertainment sector, particularly in professional, orchestral musicians. There are also constant concerns regarding noise exposure and hearing risk in "hard to control" occupations, such as farming and construction work. Although occupational noise has decreased since the early 1980s, the number of young people subject to social noise exposure has tripled. If the exposure limits from the Noise at Work Regulations are applied, discotheque music, rock concerts, as well as music from personal music players are associated with the risk of hearing loss in teenagers and young adults. Several recent research studies have increased the understanding of the pathomechanisms of acoustic trauma, the genetics of NIHL, as well as possible dietary and pharmacologic otoprotection in acoustic trauma. The results of these studies are very promising and offer grounds to expect that targeted therapies might help prevent the loss of sensory hair cells and protect the hearing of noise-exposed individuals. These studies emphasize the need to launch an improved noise exposure policy for hearing protection along with developing more efficient norms of NIHL risk assessment.

  2. Gene losses during human origins.

    Directory of Open Access Journals (Sweden)

    Xiaoxia Wang

    2006-03-01

    Full Text Available Pseudogenization is a widespread phenomenon in genome evolution, and it has been proposed to serve as an engine of evolutionary change, especially during human origins (the "less-is-more" hypothesis. However, there has been no comprehensive analysis of human-specific pseudogenes. Furthermore, it is unclear whether pseudogenization itself can be selectively favored and thus play an active role in human evolution. Here we conduct a comparative genomic analysis and a literature survey to identify 80 nonprocessed pseudogenes that were inactivated in the human lineage after its separation from the chimpanzee lineage. Many functions are involved among these genes, with chemoreception and immune response being outstandingly overrepresented, suggesting potential species-specific features in these aspects of human physiology. To explore the possibility of adaptive pseudogenization, we focus on CASPASE12, a cysteinyl aspartate proteinase participating in inflammatory and innate immune response to endotoxins. We provide population genetic evidence that the nearly complete fixation of a null allele at CASPASE12 has been driven by positive selection, probably because the null allele confers protection from severe sepsis. We estimate that the selective advantage of the null allele is about 0.9% and the pseudogenization started shortly before the out-of-Africa migration of modern humans. Interestingly, two other genes related to sepsis were also pseudogenized in humans, possibly by selection. These adaptive gene losses might have occurred because of changes in our environment or genetic background that altered the threat from or response to sepsis. The identification and analysis of human-specific pseudogenes open the door for understanding the roles of gene losses in human origins, and the demonstration that gene loss itself can be adaptive supports and extends the "less-is-more" hypothesis.

  3. Cancer Cachexia: Beyond Weight Loss.

    Science.gov (United States)

    Bruggeman, Andrew R; Kamal, Arif H; LeBlanc, Thomas W; Ma, Joseph D; Baracos, Vickie E; Roeland, Eric J

    2016-11-01

    Cancer cachexia is a multifactorial syndrome characterized by skeletal muscle loss leading to progressive functional impairment. Despite the ubiquity of cachexia in clinical practice, prevention, early identification, and intervention remain challenging. The impact of cancer cachexia on quality of life, treatment-related toxicity, physical function, and mortality are well established; however, establishing a clinically meaningful definition has proven challenging because of the focus on weight loss alone. Attempts to more comprehensively define cachexia through body composition, physical functioning, and molecular biomarkers, while promising, are yet to be routinely incorporated into clinical practice. Pharmacologic agents that have not been approved by the US Food and Drug Administration but that are currently used in cancer cachexia (ie, megestrol, dronabinol) may improve weight but not outcomes of interest such as muscle mass, physical activity, or mortality. Their routine use is limited by adverse effects. For the practicing oncologist, early identification and management of cachexia is critical. Oncologists must recognize cachexia beyond weight loss alone, focusing instead on body composition and physical functioning. In fact, becoming emaciated is a late sign of cachexia that characterizes its refractory stage. Given that cachexia is a multifactorial syndrome, it requires early identification and polymodal intervention, including optimal cancer therapy, symptom management, nutrition, exercise, and psychosocial support. Consequently, oncologists have a role in ensuring that these resources are available to their patients. In addition, in light of the promising investigational agents, it remains imperative to refer patients with cachexia to clinical trials so that available options can be expanded to effectively treat this pervasive problem.

  4. Obesity Epidemic: Pharmaceutical Weight Loss.

    Science.gov (United States)

    Curry, Stephanie A

    2017-03-01

    Obesity is a chronic disease universally defined as an excess of adipose tissue resulting in body mass index (BMI) > 30.0 kg/m2. Over the past few years, the concept of prevention has gained increased awareness, thus leading to the development of additional pharmaceutical options for the treatment of obesity since 2012. Treating obesity revolves around an individualized, multi-disciplinary approach with additional focus on a healthy and supportive lifestyle to maintain the weight loss. [Full article available at http://rimed.org/rimedicaljournal-2017-03.asp].

  5. Computer loss experience and predictions

    Science.gov (United States)

    Parker, Donn B.

    1996-03-01

    The types of losses organizations must anticipate have become more difficult to predict because of the eclectic nature of computers and the data communications and the decrease in news media reporting of computer-related losses as they become commonplace. Total business crime is conjectured to be decreasing in frequency and increasing in loss per case as a result of increasing computer use. Computer crimes are probably increasing, however, as their share of the decreasing business crime rate grows. Ultimately all business crime will involve computers in some way, and we could see a decline of both together. The important information security measures in high-loss business crime generally concern controls over authorized people engaged in unauthorized activities. Such controls include authentication of users, analysis of detailed audit records, unannounced audits, segregation of development and production systems and duties, shielding the viewing of screens, and security awareness and motivation controls in high-value transaction areas. Computer crimes that involve highly publicized intriguing computer misuse methods, such as privacy violations, radio frequency emanations eavesdropping, and computer viruses, have been reported in waves that periodically have saturated the news media during the past 20 years. We must be able to anticipate such highly publicized crimes and reduce the impact and embarrassment they cause. On the basis of our most recent experience, I propose nine new types of computer crime to be aware of: computer larceny (theft and burglary of small computers), automated hacking (use of computer programs to intrude), electronic data interchange fraud (business transaction fraud), Trojan bomb extortion and sabotage (code security inserted into others' systems that can be triggered to cause damage), LANarchy (unknown equipment in use), desktop forgery (computerized forgery and counterfeiting of documents), information anarchy (indiscriminate use of

  6. 7 CFR 760.611 - Qualifying losses, eligible causes and types of loss.

    Science.gov (United States)

    2010-01-01

    ... loss was due to poor management decisions or poor farming practices, as determined by the FSA county...) Losses caused by a failure of power supply or brownout as defined in § 760.602; (2) Losses caused by the...; (4) Losses caused by the application of chemicals; (5) Losses caused by theft or fire not caused by a...

  7. 26 CFR 1.904(f)-1 - Overall foreign loss and the overall foreign loss account.

    Science.gov (United States)

    2010-04-01

    ... States § 1.904(f)-1 Overall foreign loss and the overall foreign loss account. (a)(1) Overview of... ending before January 1, 1985, there can be three types of overall foreign losses under former section... provides rules for determining a taxpayer's overall foreign losses, for establishing overall foreign loss...

  8. 26 CFR 1.904(f)-3 - Allocation of net operating losses and net capital losses.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 9 2010-04-01 2010-04-01 false Allocation of net operating losses and net....904(f)-3 Allocation of net operating losses and net capital losses. For rules relating to the allocation of net operating losses and net capital losses, see § 1.904(g)-3T. ...

  9. Calorimetric measurements of losses in HTS cables

    DEFF Research Database (Denmark)

    Tønnesen, Ole; Veje, Niels Erling Winsløv; Rasmussen, Carsten

    2001-01-01

    A calorimetric test rig is used to investigate various loss components in a 10 m long superconducting cable model. A calorimetric technique, based on thermocouple measurements, is used to measure the losses of the 10 m long superconducting cable model. The current dependent losses are also measured...... electrically and compared with the losses obtained with the calorimetric method. The results obtained by the two methods are consistent. Based on an I2 (current) fitting procedure, the loss, caused by the eddy current generated in the stainless steel cryostat housing, and the hysteresis loss generated...

  10. Establishing soil loss tolerance: an overview

    Directory of Open Access Journals (Sweden)

    Costanza Di Stefano

    2016-09-01

    Full Text Available Soil loss tolerance is a criterion for establishing if a soil is potentially subjected to erosion risk, productivity loss and if a river presents downstream over-sedimentation or other off-site effects are present at basin scale. At first this paper reviews the concept of tolerable soil loss and summarises the available definitions and the knowledge on the recommended values and evaluating criteria. Then a threshold soil loss value, at the annual temporal scale, established for limiting riling was used for defining the classical soil loss tolerance. Finally, some research needs on tolerable soil loss are listed.

  11. [Loss of visual acuity after treatment with pipamperone].

    Science.gov (United States)

    Loos, D; Kook, P; Huber, J; Zorn, C; Lohmann, C P; Zapp, D; Maier, M

    2011-08-01

    The butyrophenone derivative pipamperone is a neuroleptic agent administered to reduce psychomotor agitation and psychotic conditions in schizophrenic psychoses. Among other things it blocks D2 receptors in the dopamine pathways of the mesolimbic system and therefore reduces excess release of dopamine in the area thought to control psychotic experiences. Dopamine also takes part in signal transduction in the visual process. Loss of visual acuity, color vision, scotoma and electrophysiological alterations were observed under treatment with different groups of neuroleptics which interfere with dopamine metabolism but have not yet been observed after therapy with pipamperone. We present the case of a young women suffering from unilateral loss of visual acuity after treatment with pipamperone.

  12. Complete linear optical isolation at the microscale with ultralow loss

    CERN Document Server

    Kim, JunHwan; Bahl, Gaurav

    2016-01-01

    Low-loss optical isolators and circulators are critical nonreciprocal components for signal routing and protection, but their chip-scale integration is not yet practical using standard photonics foundry processes. The significant challenges that confront integration of magneto-optic nonreciprocal systems on chip have made imperative the exploration of magnet free alternatives. However, none of these approaches have yet demonstrated linear optical isolation with ideal characteristics over a microscale footprint - simultaneously incorporating large contrast with ultralow forward loss - having fundamental compatibility with photonic integration in standard waveguide materials. Here we demonstrate that complete linear optical isolation can be obtained within any dielectric waveguide using only a whispering-gallery microresonator pumped by a single-frequency laser. The isolation originates from a nonreciprocal induced transparency based on a coherent light-sound interaction, with the coupling originating from the ...

  13. Generation of 1.5 Million Beam Loss Threshold Values

    CERN Document Server

    Holzer, E B; Böhlen, T T; Dehning, B; Kramer, Daniel; Ponce, L; Priebe, A; Sapinski, M; Stockner, M

    2008-01-01

    CERN's Large Hadron Collider will store an unprecedented amount of energy in its circulating beams. Beamloss monitoring (BLM) is, therefore, critical for machine protection. It must protect against the consequences (equipment damage, quenches of superconducting magnets) of excessive beam loss. About 4000 monitors will be installed at critical loss locations. Each monitor has 384 beam abort thresholds associated; for 12 integrated loss durations ($40\\mu$s to 83 s) and 32 energies (450GeV to 7 TeV). Depending on monitor location, the thresholds vary by orders of magnitude. For simplification, the monitors are grouped in 'families'. Monitors of one family protect similar magnets against equivalent loss scenarios. Therefore, they are given the same thresholds. The start-up calibration of the BLM system is required to be within a factor of five in accuracy; and the final accuracy should be a factor of two. Simulations (backed-up by control measurements) determine the relation between the BLM signal, the deposited ...

  14. Personal and social conditions potentially influencing women's hearing loss management.

    Science.gov (United States)

    Garstecki, D C; Erler, S F

    2001-12-01

    Little gender-specific data related to hearing loss and hearing loss management are available. The purpose of this investigation was to examine personal and social conditions affecting women at selected stages of the adult life course that may influence hearing loss management. In all, 191 women in three age groups, ranging from 35 to 85 years old, participated. None reported hearing problems. Participants completed a demographic data form and were given a standard audiometric evaluation to confirm age-normal hearing. Each completed assessments of speech understanding in quiet and noise, auditory signal duration discrimination, and binaural processing. Measures of hearing knowledge, behaviors, and attitudes; health-related locus of control; ego strength; and, social support were administered. Results revealed that although some variables deteriorate among subsequent age groups (i.e., hearing thresholds, central auditory processing, and ego strength), the reverse is true for others (i.e., social interaction and satisfaction with income). Age-specific sociodemographic burdens that may interfere with hearing loss management were noted. New psychosocial data are revealed against which women and men with impaired hearing may be compared.

  15. Honeybee immunity and colony losses

    Directory of Open Access Journals (Sweden)

    F. Nazzi

    2014-10-01

    Full Text Available The decline of honeybee colonies and their eventual collapse is a widespread phenomenon in the Northern hemisphere of the globe, which severely limits the beekeeping industry. This dramatic event is associated with an enhanced impact of parasites and pathogens on honeybees, which is indicative of reduced immunocompetence. The parasitic mite Varroa destructor and the vectored viral pathogens appear to play a key-role in the induction of this complex syndrome. In particular, the Deformed Wing Virus (DWV is widespread and is now considered, along with Varroa, one of the major causes of bee colony losses. Several lines of evidence indicate that this mite/DWV association severely affects the immune system of honeybees and makes them more sensitive to the action of other stress factors. The molecular mechanisms underpinning these complex interactions are currently being investigated and the emerging information has allowed the development of a new functional model, describing how different stress factors may synergistically concur in the induction of bee immune alteration and health decline. This provides a new logical framework in which to interpret the proposed multifactorial origin of bee colony losses and sets the stage for a more comprehensive and integrated analysis of the effect that multiple stress agents may have on honeybees.

  16. Multimodal signalling in estrildid finches

    DEFF Research Database (Denmark)

    Gomes, A. C. R.; Funghi, C.; Soma, M.

    2017-01-01

    Sexual traits (e.g. visual ornaments, acoustic signals, courtship behaviour) are often displayed together as multimodal signals. Some hypotheses predict joint evolution of different sexual signals (e.g. to increase the efficiency of communication) or that different signals trade off with each other...... in reproduction, dance with commonness and habitat type, whereas colour ornamentation was shown previously to correlate mostly with gregariousness. We conclude that multimodal signals evolve in response to various socio-ecological traits, suggesting the accumulation of distinct signalling functions....

  17. Biomedical signal and image processing

    CERN Document Server

    Najarian, Kayvan

    2012-01-01

    INTRODUCTION TO DIGITAL SIGNAL AND IMAGE PROCESSINGSignals and Biomedical Signal ProcessingIntroduction and OverviewWhat is a ""Signal""?Analog, Discrete, and Digital SignalsProcessing and Transformation of SignalsSignal Processing for Feature ExtractionSome Characteristics of Digital ImagesSummaryProblemsFourier TransformIntroduction and OverviewOne-Dimensional Continuous Fourier TransformSampling and NYQUIST RateOne-Dimensional Discrete Fourier TransformTwo-Dimensional Discrete Fourier TransformFilter DesignSummaryProblemsImage Filtering, Enhancement, and RestorationIntroduction and Overview

  18. Signal analyser, the software support for education of signal processing

    Directory of Open Access Journals (Sweden)

    Tùma Jiøí

    2003-12-01

    Full Text Available The paper deals with the software that is supporting signal-processing lectures given for students of mechanical engineering. An application, named Signal Analyser is written in Visual Basic 6.0 language so it is working under Windows operating systems. The main idea is to demonstrate spectral analysis of signals that are taken from measurements in industry or synthesised by an incorporate signal generator.

  19. Trolox Prevents Osteoclastogenesis by Suppressing RANKL Expression and Signaling*S⃞

    OpenAIRE

    Lee, Jong-Ho; Kim, Ha-Neui; Yang, Daum; Jung, Kyoungsuk; Kim, Hyun-Man; Kim, Hong-Hee; Ha, Hyunil; Lee, Zang Hee

    2009-01-01

    Excessive receptor activator of NF-κB ligand (RANKL) signaling causes enhanced osteoclast formation and bone resorption. Thus, down-regulation of RANKL expression or its downstream signals may be a therapeutic approach to the treatment of pathological bone loss. In this study, we investigated the effects of Trolox, a water-soluble vitamin E analogue, on osteoclastogenesis and RANKL signaling. Trolox potently inhibited interleukin-1-induced osteoclast formation in bone ...

  20. Unified Processing Structure for Communication and Navigation signals in modems for lightweight satellite stations

    Directory of Open Access Journals (Sweden)

    Y.N. Antonov-Antipov (R.I.P.

    2012-10-01

    Full Text Available The present article shows the design and test of a unified-processing device for detection and demodulation of narrowand broadband communication signals, as well as navigation signals from GLONASS and GPS systems. The specificprocessing for each type of signal is described within the general framework of the proposed device. Performanceindicators, such as symbol error probability (SEP and energy losses, were computed using simulations of the deviceand the corresponding results are presented for discussion.

  1. Fuzzy Adaptive Particle Swarm Optimization for Power Loss Minimisation in Distribution Systems Using Optimal Load Response

    DEFF Research Database (Denmark)

    Hu, Weihao; Chen, Zhe; Bak-Jensen, Birgitte

    2014-01-01

    power loss minimization in distribution systems. In this paper, a new method to achieve power loss minimization in distribution systems by using a price signal to guide the demand side management is proposed. A fuzzy adaptive particle swarm optimization (FAPSO) is used as a tool for the power loss......Consumers may decide to modify the profile of their demand from high price periods to low price periods in order to reduce their electricity costs. This optimal load response to electricity prices for demand side management generates different load profiles and provides an opportunity to achieve...

  2. Nitric oxide signaling in hypoxia.

    Science.gov (United States)

    Ho, J J David; Man, H S Jeffrey; Marsden, Philip A

    2012-03-01

    Endothelial-derived nitric oxide (NO) is classically viewed as a regulator of vasomotor tone. NO plays an important role in regulating O(2) delivery through paracrine control of vasomotor tone locally and cardiovascular and respiratory responses centrally. Very soon after the cloning and functional characterization of the endothelial nitric oxide synthase (eNOS), studies on the interaction between O(2) and NO made the paradoxical finding that hypoxia led to decreases in eNOS expression and function. Why would decreases in O(2) content in tissues elicit a loss of a potent endothelial-derived vasodilator? We now know that restricting our view of NO as a regulator of vasomotor tone or blood pressure limited deeper levels of mechanistic insight. Exciting new studies indicate that functional interactions between NO and O(2) exhibit profound complexity and are relevant to diseases states, especially those associated with hypoxia in tissues. NOS isoforms catalytically require O(2). Hypoxia regulates steady-state expression of the mRNA and protein abundance of the NOS enzymes. Animals genetically deficient in NOS isoforms have perturbations in their ability to adapt to changes in O(2) supply or demand. Most interestingly, the intracellular pathways for O(2) sensing that evolved to ensure an appropriate balance of O(2) delivery and utilization intersect with NO signaling networks. Recent studies demonstrate that hypoxia-inducible factor (HIF) stabilization and transcriptional activity is achieved through two parallel pathways: (1) a decrease in O(2)-dependent prolyl hydroxylation of HIF and (2) S-nitrosylation of HIF pathway components. Recent findings support a role for S-nitrosothiols as hypoxia-mimetics in certain biological and/or disease settings, such as living at high altitude, exposure to small molecules that can bind NO, or anemia.

  3. Trolox prevents osteoclastogenesis by suppressing RANKL expression and signaling.

    Science.gov (United States)

    Lee, Jong-Ho; Kim, Ha-Neui; Yang, Daum; Jung, Kyoungsuk; Kim, Hyun-Man; Kim, Hong-Hee; Ha, Hyunil; Lee, Zang Hee

    2009-05-15

    Excessive receptor activator of NF-kappaB ligand (RANKL) signaling causes enhanced osteoclast formation and bone resorption. Thus, down-regulation of RANKL expression or its downstream signals may be a therapeutic approach to the treatment of pathological bone loss. In this study, we investigated the effects of Trolox, a water-soluble vitamin E analogue, on osteoclastogenesis and RANKL signaling. Trolox potently inhibited interleukin-1-induced osteoclast formation in bone marrow cell-osteoblast coculture by abrogating RANKL induction in osteoblasts. This RANKL reduction was attributed to the reduced production of prostaglandin E(2) via a down-regulation of cyclooxygenase-2 activity. We also found that Trolox inhibited osteoclast formation from bone marrow macrophages induced by macrophage colony-stimulating factor plus RANKL in a reversible manner. Trolox was effective only when present during the early stage of culture, which implies that it targets early osteoclast precursors. Pretreatment with Trolox did not affect RANKL-induced early signaling pathways, including MAPKs, NF-kappaB, and Akt. We found that Trolox down-regulated the induction by RANKL of c-Fos protein by suppressing its translation. Ectopic overexpression of c-Fos rescued the inhibition of osteoclastogenesis by Trolox in bone marrow macrophages. Trolox also suppressed interleukin-1-induced osteoclast formation and bone loss in mouse calvarial bone. Taken together, our findings indicate that Trolox prevents osteoclast formation and bone loss by inhibiting both RANKL induction in osteoblasts and c-Fos expression in osteoclast precursors.

  4. Global Volcano Proportional Economic Loss Risk Deciles

    Data.gov (United States)

    National Aeronautics and Space Administration — Global Volcano Proportional Economic Loss Risk Deciles is a 2.5 minute grid of volcano hazard economic loss as proportions of Gross Domestic Product (GDP) per...

  5. Global Multihazard Total Economic Loss Risk Deciles

    Data.gov (United States)

    National Aeronautics and Space Administration — Global Multihazard Total Economic Loss Risk Deciles is a 2.5 minute grid of global multihazard total economic loss risks. First, for each of the considered hazards...

  6. FAQs of Pregnancy Loss and Miscarriage

    Science.gov (United States)

    ... Other FAQs Share Facebook Twitter Pinterest Email Print Pregnancy Loss: Other FAQs Basic information for topics, such ... anything a woman can do to prevent a pregnancy loss? Most of the time, a woman cannot ...

  7. Global Drought Proportional Economic Loss Risk Deciles

    Data.gov (United States)

    National Aeronautics and Space Administration — Global Drought Proportional Economic Loss Risk Deciles is a 2.5 minute grid of drought hazard economic loss as proportions of Gross Domestic Product (GDP) per...

  8. Global Drought Total Economic Loss Risk Deciles

    Data.gov (United States)

    National Aeronautics and Space Administration — Global Drought Total Economic Loss Risk Deciles is a 2.5 minute grid of global drought total economic loss risks. A process of spatially allocating Gross Domestic...

  9. Global Volcano Total Economic Loss Risk Deciles

    Data.gov (United States)

    National Aeronautics and Space Administration — Global Volcano Total Economic Loss Risk Deciles is a 2.5 minute grid of global volcano total economic loss risks. First, subnational distributions of Gross Domestic...

  10. Managing Chemotherapy Side Effects: Hair Loss (Alopecia)

    Science.gov (United States)

    ... C ancer I nstitute Managing Chemotherapy Side Effects Hair Loss (Alopecia) “Losing my hair was hard at first. Then ... and anywhere on your body may fall out. Hair loss is called alopecia. When will my hair start ...

  11. Global Multihazard Proportional Economic Loss Risk Deciles

    Data.gov (United States)

    National Aeronautics and Space Administration — Global Multihazard Proportional Economic Loss Risks is a 2.5 minute grid of a multihazard-based economic loss risk as a proportion of the economic productivity of...

  12. Global Flood Total Economic Loss Risk Deciles

    Data.gov (United States)

    National Aeronautics and Space Administration — Global Flood Total Economic Loss Risk Deciles is a 2.5 minute grid of global flood total economic loss risks. A process of spatially allocating Gross Domestic...

  13. Global Landslide Total Economic Loss Risk Deciles

    Data.gov (United States)

    National Aeronautics and Space Administration — Global Landslide Total Economic Loss Risk Deciles is a 2.5 minute grid of global landslide total economic loss risks. A process of spatially allocating Gross...

  14. Global Earthquake Total Economic Loss Risk Deciles

    Data.gov (United States)

    National Aeronautics and Space Administration — Global Earthquake Total Economic Loss Risk Deciles is a 2.5 minute grid of global earthquake total economic loss risks. A process of spatially allocating Gross...

  15. Global Landslide Proportional Economic Loss Risk Deciles

    Data.gov (United States)

    National Aeronautics and Space Administration — Global Landslide Proportional Economic Loss Risk Deciles is a 2.5 minute grid of landslide hazard economic loss as proportions of Gross Domestic Product (GDP) per...

  16. Global Flood Proportional Economic Loss Risk Deciles

    Data.gov (United States)

    National Aeronautics and Space Administration — Global Flood Proportional Economic Loss Risk Deciles is a 2.5 minute grid of flood hazard economic loss as proportions of Gross Domestic Product (GDP) per analytical...

  17. Global Drought Total Economic Loss Risk Deciles

    Data.gov (United States)

    National Aeronautics and Space Administration — Global Drought Total Economic Loss Risk Deciles is a 2.5 by 2.5 minute grid of global drought total economic loss risks. A process of spatially allocating Gross...

  18. Global Cyclone Total Economic Loss Risk Deciles

    Data.gov (United States)

    National Aeronautics and Space Administration — Global Cyclone Total Economic Loss Risk Deciles is a 2.5 minute grid of global cyclone total economic loss risks. A process of spatially allocating Gross Domestic...

  19. Weight Loss Surgery: An Option for Teens?

    Science.gov (United States)

    ... Vaccine Preventable Diseases Healthy Children > Health Issues > Conditions > Obesity > Weight Loss Surgery: An Option for Teens? Health Issues Listen ... for extremely overweight adolescents for whom more conservative weight loss ... obesity-related medical conditions such as high blood pressure , ...

  20. Genetics Home Reference: nonsyndromic hearing loss

    Science.gov (United States)

    ... factor for hearing loss. Age-related hearing loss (presbycusis) is thought to have both genetic and environmental ... Encyclopedia: Hearing or speech impairment - resources Health Topic: Hearing Disorders and Deafness Health Topic: Hearing Problems in Children Health Topic: ...