The haptic and the visual flash-lag effect and the role of flash characteristics.

Directory of Open Access Journals (Sweden)

Knut Drewing

Full Text Available When a short flash occurs in spatial alignment with a moving object, the moving object is seen ahead the stationary one. Similar to this visual "flash-lag effect" (FLE it has been recently observed for the haptic sense that participants judge a moving hand to be ahead a stationary hand when judged at the moment of a short vibration ("haptic flash" that is applied when the two hands are spatially aligned. We further investigated the haptic FLE. First, we compared participants' performance in two isosensory visual or haptic conditions, in which moving object and flash were presented only in a single modality (visual: sphere and short color change, haptic: hand and vibration, and two bisensory conditions, in which the moving object was presented in both modalities (hand aligned with visible sphere, but the flash was presented only visually or only haptically. The experiment aimed to disentangle contributions of the flash's and the objects' modalities to the FLEs in haptics versus vision. We observed a FLE when the flash was visually displayed, both when the moving object was visual and visuo-haptic. Because the position of a visual flash, but not of an analogue haptic flash, is misjudged relative to a same visuo-haptic moving object, the difference between visual and haptic conditions can be fully attributed to characteristics of the flash. The second experiment confirmed that a haptic FLE can be observed depending on flash characteristics: the FLE increases with decreasing intensity of the flash (slightly modulated by flash duration, which had been previously observed for vision. These findings underline the high relevance of flash characteristics in different senses, and thus fit well with the temporal-sampling framework, where the flash triggers a high-level, supra-modal process of position judgement, the time point of which further depends on the processing time of the flash.

Characterizing the source properties of terrestrial gamma ray flashes

Science.gov (United States)

Dwyer, Joseph R.; Liu, Ningyu; Eric Grove, J.; Rassoul, Hamid; Smith, David M.

2017-08-01

Monte Carlo simulations are used to determine source properties of terrestrial gamma ray flashes (TGFs) as a function of atmospheric column depth and beaming geometry. The total mass per unit area traversed by all the runaway electrons (i.e., the total grammage) during a TGF, Ξ, is introduced, defined to be the total distance traveled by all the runaway electrons along the electric field lines multiplied by the local air mass density along their paths. It is shown that key properties of TGFs may be directly calculated from Ξ and its time derivative, including the gamma ray emission rate, the current moment, and the optical power of the TGF. For the calculations presented in this paper, a standard TGF gamma ray fluence, F0 = 0.1 cm-2 above 100 keV for a spacecraft altitude of 500 km, and a standard total grammage, Ξ0 = 1018 g/cm2, are introduced, and results are presented in terms of these values. In particular, the current moments caused by the runaway electrons and their accompanying ionization are found for a standard TGF fluence, as a function of source altitude and beaming geometry, allowing a direct comparison between the gamma rays measured in low-Earth orbit and the VLF-LF radio frequency emissions recorded on the ground. Such comparisons should help test and constrain TGF models and help identify the roles of lightning leaders and streamers in the production of TGFs.

The Fermi Gamma-ray Burst Monitor (GBM) Terrestrial Gamma-ray Flash (TGF) Catalog

Science.gov (United States)

Briggs, M. S.; Roberts, O.; Fitzpatrick, G.; Stanbro, M.; Cramer, E.; Mailyan, B. G.; McBreen, S.; Connaughton, V.; Grove, J. E.; Chekhtman, A.; Holzworth, R.

2017-12-01

The revised Second Fermi GBM TGF catalog includes data on 4144 TGFs detected by the Fermi Gamma-ray Burst Monitor through 2016 July 31. The catalog includes 686 bright TGFs there were detected in orbit and 4135 TGFs that were discovered by ground analysis of GBM data (the two samples overlap). Thirty of the events may have been detected as electrons and positrons rather than gamma-rays: Terrestrial Electron Beams (TEBs). We also provide results from correlating the GBM TGFs with VLF radio detections of the World Wide Lightning Location Network (WWLLN). TGFs with WWLLN associations have their localization uncertainties improved from 800 to 10 km, making it possible to identify specific thunderstorms responsible for the TGFs and opening up new types of scientific investigations. There are 1544 TGFs with WWLLN associations; maps are provided for these and the other TGFs of the catalog. The data tables of the catalog are available for use by the scientific community at the Fermi Science Support Center, at https://fermi.gsfc.nasa.gov/ssc/data/access/gbm/tgf/.

Comparison of Terrestrial Gamma Ray Flash Simulations with Observations by Fermi

Science.gov (United States)

2016-10-31

all the runaway elections (i.e., the total grammage) during a TGF, X , is introduced, defined to be the total distance traveled by all the runaway ... runaway electrons and their accompanying ionization are found for a standard TGF fluence, as a function of source altitude and beaming geometry...Such comparisons should help test and constrain TGF models and help identify the roles of lightning leaders and streamers in the production of TGFs. As

Terrestrial gamma ray flash production by active lightning leader channels

OpenAIRE

İnan, Umran Savaş; Carlson, B. E.; Lehtinen, N. G.

2017-01-01

The production of terrestrial gamma ray flashes (TGFs) requires a seed energetic electron source and a strong electric field. Lightning leaders naturally provide seed electrons by cold runaway and strong electric fields by charge accumulation on the channel. We model possible TGF production in such fields by simulating the charges and currents on the channel. The resulting electric fields then drive simulations of runaway relativistic electron avalanche and photon emission. Photon spectra and...

Expression of transforming growth factor beta (TGF beta) receptors and expression of TGF beta 1, TGF beta 2 and TGF beta 3 in human small cell lung cancer cell lines

DEFF Research Database (Denmark)

Damstrup, L; Rygaard, K; Spang-Thomsen, M

1993-01-01

A panel of 21 small cell lung cancer cell (SCLC) lines were examined for the presence of Transforming growth factor beta receptors (TGF beta-r) and the expression of TGF beta mRNAs. By the radioreceptor assay we found high affinity receptors to be expressed in six cell lines. scatchard analysis......(r) = 65,000 and 90,000 and the betaglycan (type III) with M(r) = 280,000. Northern blotting showed expression of TGF beta 1 mRNA in ten, TGF beta 2 mRNA in two and TGF beta 3 mRNA in seven cell lines. Our results provide, for the first time, evidence that a large proportion of a broad panel of SCLC cell...... lines express TGF beta-receptors and also produce TGF beta mRNAs....

Regulation of the Bioavailability of TGF-β and TGF-β-Related Proteins

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Robertson, Ian B.; Rifkin, Daniel B.

2016-01-01

The bioavailability of members of the transforming growth factor β (TGF-β) family is controlled by a number of mechanisms. Bona fide TGF-β is sequestered into the matrix in a latent state and must be activated before it can bind to its receptors. Here, we review the molecules and mechanisms that regulate the bioavailability of TGF-β and compare these mechanisms with those used to regulate other TGF-β family members. We also assess the physiological significance of various latent TGF-β activators, as well as other extracellular modulators of TGF-β family signaling, by examining the available in vivo data from knockout mouse models and other biological systems. PMID:27252363

Modeling terrestrial gamma ray flashes produced by relativistic feedback discharges

Science.gov (United States)

Liu, Ningyu; Dwyer, Joseph R.

2013-05-01

This paper reports a modeling study of terrestrial gamma ray flashes (TGFs) produced by relativistic feedback discharges. Terrestrial gamma ray flashes are intense energetic radiation originating from the Earth's atmosphere that has been observed by spacecraft. They are produced by bremsstrahlung interactions of energetic electrons, known as runaway electrons, with air atoms. An efficient physical mechanism for producing large fluxes of the runaway electrons to make the TGFs is the relativistic feedback discharge, where seed runaway electrons are generated by positrons and X-rays, products of the discharge itself. Once the relativistic feedback discharge becomes self-sustaining, an exponentially increasing number of relativistic electron avalanches propagate through the same high-field region inside the thundercloud until the electric field is partially discharged by the ionization created by the discharge. The modeling results indicate that the durations of the TGF pulses produced by the relativistic feedback discharge vary from tens of microseconds to several milliseconds, encompassing all durations of the TGFs observed so far. In addition, when a sufficiently large potential difference is available in thunderclouds, a self-propagating discharge known as the relativistic feedback streamer can be formed, which propagates like a conventional positive streamer. For the relativistic feedback streamer, the positive feedback mechanism of runaway electron production by the positrons and X-rays plays a similar role as the photoionization for the conventional positive streamer. The simulation results of the relativistic feedback streamer show that a sequence of TGF pulses with varying durations can be produced by the streamer. The relativistic streamer may initially propagate with a pulsed manner and turn into a continuous propagation mode at a later stage. Milliseconds long TGF pulses can be produced by the feedback streamer during its continuous propagation. However

Terrestrial gamma-ray flashes

Science.gov (United States)

Marisaldi, Martino; Fuschino, Fabio; Labanti, Claudio; Tavani, Marco; Argan, Andrea; Del Monte, Ettore; Longo, Francesco; Barbiellini, Guido; Giuliani, Andrea; Trois, Alessio; Bulgarelli, Andrea; Gianotti, Fulvio; Trifoglio, Massimo

2013-08-01

Lightning and thunderstorm systems in general have been recently recognized as powerful particle accelerators, capable of producing electrons, positrons, gamma-rays and neutrons with energies as high as several tens of MeV. In fact, these natural systems turn out to be the highest energy and most efficient natural particle accelerators on Earth. Terrestrial Gamma-ray Flashes (TGFs) are millisecond long, very intense bursts of gamma-rays and are one of the most intriguing manifestation of these natural accelerators. Only three currently operative missions are capable of detecting TGFs from space: the RHESSI, Fermi and AGILE satellites. In this paper we review the characteristics of TGFs, including energy spectrum, timing structure, beam geometry and correlation with lightning, and the basic principles of the associated production models. Then we focus on the recent AGILE discoveries concerning the high energy extension of the TGF spectrum up to 100 MeV, which is difficult to reconcile with current theoretical models.

Terrestrial gamma-ray flashes

International Nuclear Information System (INIS)

Marisaldi, Martino; Fuschino, Fabio; Labanti, Claudio; Tavani, Marco; Argan, Andrea; Del Monte, Ettore; Longo, Francesco; Barbiellini, Guido; Giuliani, Andrea; Trois, Alessio; Bulgarelli, Andrea; Gianotti, Fulvio; Trifoglio, Massimo

2013-01-01

Lightning and thunderstorm systems in general have been recently recognized as powerful particle accelerators, capable of producing electrons, positrons, gamma-rays and neutrons with energies as high as several tens of MeV. In fact, these natural systems turn out to be the highest energy and most efficient natural particle accelerators on Earth. Terrestrial Gamma-ray Flashes (TGFs) are millisecond long, very intense bursts of gamma-rays and are one of the most intriguing manifestation of these natural accelerators. Only three currently operative missions are capable of detecting TGFs from space: the RHESSI, Fermi and AGILE satellites. In this paper we review the characteristics of TGFs, including energy spectrum, timing structure, beam geometry and correlation with lightning, and the basic principles of the associated production models. Then we focus on the recent AGILE discoveries concerning the high energy extension of the TGF spectrum up to 100 MeV, which is difficult to reconcile with current theoretical models

Ultra-Fast Flash Observatory for observation of early photons from gamma ray bursts

DEFF Research Database (Denmark)

Park, I. H.; Ahmad, S.; Barrillon, P.

2012-01-01

We describe the space project of Ultra-Fast Flash Observatory (UFFO) which will observe early optical photons from gamma-ray bursts (GRBs) with a sub-second optical response, for the first time. The UFFO will probe the early optical rise of GRBs, opening a completely new frontier in GRB and trans...

In silico investigation of ADAM12 effect on TGF-β receptors trafficking

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LeMeur Nolwenn

2009-09-01

Full Text Available Abstract Background The transforming growth factor beta is known to have pleiotropic effects, including differentiation, proliferation and apoptosis. However the underlying mechanisms remain poorly understood. The regulation and effect of TGF-β signaling is complex and highly depends on specific protein context. In liver, we have recently showed that the disintegrin and metalloproteinase ADAM12 interacts with TGF-β receptors and modulates their trafficking among membranes, a crucial point in TGF-β signaling and development of fibrosis. The present study aims to better understand how ADAM12 impacts on TGF-β receptors trafficking and TGF-β signaling. Findings We extracted qualitative biological observations from experimental data and defined a family of models producing a behavior compatible with the presence of ADAM12. We computationally explored the properties of this family of models which allowed us to make novel predictions. We predict that ADAM12 increases TGF-β receptors internalization rate between the cell surface and the endosomal membrane. It also appears that ADAM12 modifies TGF-β signaling shape favoring a permanent response by removing the transient component observed under physiological conditions. Conclusion In this work, confronting differential models with qualitative biological observations, we obtained predictions giving new insights into the role of ADAM12 in TGF-β signaling and hepatic fibrosis process.

Plasma TGF beta level in rats after hemithoracic irradiation

NARCIS (Netherlands)

Vujaskovic, Z; Down, JD; vanWaarde, MAWH; vanAssen, AJ; Szabo, BG; Konings, AWT

Changes in TGF-beta plasma levels were observed 18 weeks after hemithoracic irradiation in rats. This coincides with an increase in the breathing frequency, being most pronounced between 22 and 28 weeks after irradiation. The correlation suggests a potential role of the circulating TGF-beta in the

Electron Acceleration by Stochastic Electric Fields in Thunderstorms: Terrestrial Gamma-Ray Flashes

Science.gov (United States)

Alnussirat, S.; Miller, J. A.; Christian, H. J., Jr.; Fishman, G. J.

2016-12-01

Terrestrial gamma-ray flashes (TGFs) are energetic pulses of photons, which are intense and short, originating in the atmosphere during thunderstorm activity. Despite the number of observations, the production mechanism(s) of TGFs and other energetic particles is not well understood. However, two mechanisms have been suggested as a source of TGFs: (1) the relativistic runaway electron avalanche mechanism (RREA), and (2) the lightning leader mechanism. The RREA can account for the TGF observations, but requires restrictive or unrealistic assumptions. The lightning leader channel is also expected to produce runaway electrons, but through inhomogeneous, small scale, strong electric fields. In this work we use the Boltzmann equation to model the electron acceleration by the lightning leader mechanism, and we derive the gamma-ray spectrum from the electron distribution function. The electric fields at the tip of the leaders are assumed to be stochastic in space and time. Since the physics involved in the lightening leader is not known, we test different cases of the stochastic acceleration agent. From this modeling we hope to investigate the possibility and efficiency of stochastic acceleration in thunderstorm.

Menopausal Hot Flashes and White Matter Hyperintensities

Science.gov (United States)

Thurston, Rebecca C.; Aizenstein, Howard J.; Derby, Carol A.; Sejdić, Ervin; Maki, Pauline M.

2015-01-01

Objective Hot flashes are the classic menopausal symptom. Emerging data links hot flashes to cardiovascular disease (CVD) risk, yet how hot flashes are related to brain health is poorly understood. We examined the relationship between hot flashes - measured via physiologic monitor and self-report - and white matter hyperintensities (WMH) among midlife women. Methods Twenty midlife women ages 40-60 without clinical CVD, with their uterus and both ovaries, and not taking hormone therapy were recruited. Women underwent 24 hours of ambulatory physiologic and diary hot flash monitoring to quantify hot flashes; magnetic resonance imaging to assess WMH burden; 72 hours of actigraphy and questionnaires to quantify sleep; and a blood draw, questionnaires, and physical measures to quantify demographics and CVD risk factors. Test of a priori hypotheses regarding relations between physiologically-monitored and self-reported wake and sleep hot flashes and WMH were conducted in linear regression models. Results More physiologically-monitored hot flashes during sleep were associated with greater WMH, controlling for age, race, and body mass index [beta(standard error)=.0002 (.0001), p=.03]. Findings persisted controlling for sleep characteristics and additional CVD risk factors. No relations were observed for self-reported hot flashes. Conclusions More physiologically-monitored hot flashes during sleep were associated with greater WMH burden among midlife women free of clinical CVD. Results suggest that relations between hot flashes and CVD risk observed in the periphery may extend to the brain. Future work should consider the unique role of sleep hot flashes in brain health. PMID:26057822

VHF lightning mapping observations of a triggered lightning flash

Science.gov (United States)

Edens, H. E.; Eack, K. B.; Eastvedt, E. M.; Trueblood, J. J.; Winn, W. P.; Krehbiel, P. R.; Aulich, G. D.; Hunyady, S. J.; Murray, W. C.; Rison, W.; Behnke, S. A.; Thomas, R. J.

2012-10-01

On 3 August 2010 an extensive lightning flash was triggered over Langmuir Laboratory in New Mexico. The upward positive leader propagated into the storm's midlevel negative charge region, extending over a horizontal area of 13 × 13 km and 7.5 km altitude. The storm had a normal-polarity tripolar charge structure with upper positive charge over midlevel negative charge. Lightning Mapping Array (LMA) observations were used to estimate positive leader velocities along various branches, which were in the range of 1-3 × 104 m s-1, slower than in other studies. The upward positive leader initiated at 3.4 km altitude, but was mapped only above 4.0 km altitude after the onset of retrograde negative breakdown, indicating a change in leader propagation and VHF emissions. The observations suggest that both positive and negative breakdown produce VHF emissions that can be located by time-of-arrival systems, and that not all VHF emissions occurring along positive leader channels are associated with retrograde negative breakdown.

Estimation of the Relative Severity of Floods in Small Ungauged Catchments for Preliminary Observations on Flash Flood Preparedness: A Case Study in Korea

Science.gov (United States)

Kim, Eung Seok; Choi, Hyun Il

2012-01-01

An increase in the occurrence of sudden local flooding of great volume and short duration has caused significant danger and loss of life and property in Korea as well as many other parts of the World. Since such floods usually accompanied by rapid runoff and debris flow rise quite quickly with little or no advance warning to prevent flood damage, this study presents a new flash flood indexing methodology to promptly provide preliminary observations regarding emergency preparedness and response to flash flood disasters in small ungauged catchments. Flood runoff hydrographs are generated from a rainfall-runoff model for the annual maximum rainfall series of long-term observed data in the two selected small ungauged catchments. The relative flood severity factors quantifying characteristics of flood runoff hydrographs are standardized by the highest recorded maximum value, and then averaged to obtain the flash flood index only for flash flood events in each study catchment. It is expected that the regression equations between the proposed flash flood index and rainfall characteristics can provide the basis database of the preliminary information for forecasting the local flood severity in order to facilitate flash flood preparedness in small ungauged catchments. PMID:22690208

TGF-β-activated kinase-1: New insights into the mechanism of TGF-β signaling and kidney disease

Directory of Open Access Journals (Sweden)

Sung Il Kim

2012-06-01

Full Text Available Transforming growth factor-β (TGF-β is a multifunctional cytokine that regulates a wide variety of cellular functions, including cell growth, cellular differentiation, apoptosis, and wound healing. TGF-β1, the prototype member of the TGF-β superfamily, is well established as a central mediator of renal fibrosis. In chronic kidney disease, dysregulation of expression and activation of TGF-β1 results in the relentless synthesis and accumulation of extracellular matrix proteins that lead to the development of glomerulosclerosis and tubulointerstitial fibrosis, and ultimately to end-stage renal disease. Therefore, specific targeting of the TGF-β signaling pathway is seemingly an attractive molecular therapeutic strategy in chronic kidney disease. Accumulating evidence demonstrates that the multifunctionality of TGF-β1 is connected with the complexity of its cell signaling networks. TGF-β1 signals through the interaction of type I and type II receptors to activate distinct intracellular pathways. Although the Smad signaling pathway is known as a canonical pathway induced by TGF-β1, and has been the focus of many previous reviews, importantly TGF-β1 also induces various Smad-independent signaling pathways. In this review, we describe evidence that supports current insights into the mechanism and function of TGF-β-activated kinase 1 (TAK1, which has emerged as a critical signaling molecule in TGF-β-induced Smad-independent signaling pathways. We also discuss the functional role of TAK1 in mediating the profibrotic effects of TGF-β1.

High LET Radiation Can Enhance TGF(Beta) Induced EMT and Cross-Talk with ATM Pathways

Science.gov (United States)

Wang, Minli; Hada, Megumi; Huff, Janice; Pluth, Janice M.; Anderson, Janniffer; ONeill, Peter; Cucinotta, Francis A.

2010-01-01

The TGF(Beta) pathway has been shown to regulate or directly interact with the ATM pathway in the response to radiation in mammary epithelial cells. We investigated possible interactions between the TGF(Beta) and ATM pathways following simulated space radiation using hTERT immortalized human esophageal epithelial cells (EPC-hTERT), mink lung epithelial cells (Mv1lu), and several human fibroblast cell lines. TGF(Beta) is a key modulator of the Epithelial-Mesenchymal Transition (EMT), important in cancer progression and metastasis. The implication of EMT by radiation also has several lines of developing evidence, however is poorly understood. The identification of TGF(Beta) induced EMT can be shown in changes to morphology, related gene over expression or down regulation, which can be detected by RT-PCR, and immunostaining and western blotting. In this study, we have observed morphologic and molecular alternations consistent with EMT after Mv1lu cells were treated with TGF(Beta) High LET radiation enhanced TGF(Beta) mediated EMT with a dose as low as 0.1Gy. In order to consider the TGF(Beta) interaction with ATM we used a potent ATM inhibitor Ku55933 and investigated gene expression changes and Smad signaling kinetics. Ku559933 was observed to reverse TGF(Beta) induced EMT, while this was not observed in dual treated cells (radiation+TGF(Beta)). In EPC-hTERT cells, TGF(Beta) alone was not able to induce EMT after 3 days of application. A combined treatment with high LET, however, significantly caused the alteration of EMT markers. To study the function of p53 in the process of EMT, we knocked down P53 through RNA interference. Morphology changes associated with EMT were observed in epithelial cells with silenced p53. Our study indicates: high LET radiation can enhance TGF(Beta) induced EMT; while ATM is triggering the process of TGF(Beta)-induced EMT, p53 might be an essential repressor for EMT phenotypes.

Flash flood forecasting, warning and risk management: the HYDRATE project

International Nuclear Information System (INIS)

Borga, M.; Anagnostou, E.N.; Bloeschl, G.; Creutin, J.-D.

2011-01-01

Highlights: → We characterize flash flood events in various regions of Europe. → We provide guidance to improve observations and monitoring of flash floods. → Flash floods are associated to orography and are influenced by initial soil moisture conditions. → Models for flash flood forecasting and flash flood hazard assessment are illustrated and discussed. → We examine implications for flood risk policy and discuss recommendations received from end users. - Abstract: The management of flash flood hazards and risks is a critical component of public safety and quality of life. Flash-floods develop at space and time scales that conventional observation systems are not able to monitor for rainfall and river discharge. Consequently, the atmospheric and hydrological generating mechanisms of flash-floods are poorly understood, leading to highly uncertain forecasts of these events. The objective of the HYDRATE project has been to improve the scientific basis of flash flood forecasting by advancing and harmonising a European-wide innovative flash flood observation strategy and developing a coherent set of technologies and tools for effective early warning systems. To this end, the project included actions on the organization of the existing flash flood data patrimony across Europe. The final aim of HYDRATE was to enhance the capability of flash flood forecasting in ungauged basins by exploiting the extended availability of flash flood data and the improved process understanding. This paper provides a review of the work conducted in HYDRATE with a special emphasis on how this body of research can contribute to guide the policy-life cycle concerning flash flood risk management.

TGF-β receptors, in a Smad-independent manner, are required for terminal skeletal muscle differentiation

International Nuclear Information System (INIS)

Droguett, Rebeca; Cabello-Verrugio, Claudio; Santander, Cristian; Brandan, Enrique

2010-01-01

Skeletal muscle differentiation is strongly inhibited by transforming growth factor type β (TGF-β), although muscle formation as well as regeneration normally occurs in an environment rich in this growth factor. In this study, we evaluated the role of intracellular regulatory Smads proteins as well as TGF-β-receptors (TGF-β-Rs) during skeletal muscle differentiation. We found a decrease of TGF-β signaling during differentiation. This phenomenon is explained by a decline in the levels of the regulatory proteins Smad-2, -3, and -4, a decrease in the phosphorylation of Smad-2 and lost of nuclear translocation of Smad-3 and -4 in response to TGF-β. No change in the levels and inhibitory function of Smad-7 was observed. In contrast, we found that TGF-β-R type I (TGF-β-RI) and type II (TGF-β-RII) increased on the cell surface during skeletal muscle differentiation. To analyze the direct role of the serine/threonine kinase activities of TGF-β-Rs, we used the specific inhibitor SB 431542 and the dominant-negative form of TGF-β-RII lacking the cytoplasmic domain. The TGF-β-Rs were important for successful muscle formation, determined by the induction of myogenin, creatine kinase activity, and myosin. Silencing of Smad-2/3 expression by specific siRNA treatments accelerated myogenin, myosin expression, and myotube formation; although when SB 431542 was present inhibition in myosin induction and myotube formation was observed, suggesting that these last steps of skeletal muscle differentiation require active TGF-β-Rs. These results suggest that both down-regulation of Smad regulatory proteins and cell signaling through the TGF-β receptors independent of Smad proteins are essential for skeletal muscle differentiation.

TGF-{beta} receptors, in a Smad-independent manner, are required for terminal skeletal muscle differentiation

Energy Technology Data Exchange (ETDEWEB)

Droguett, Rebeca; Cabello-Verrugio, Claudio; Santander, Cristian [Centro de Regulacion Celular y Patologia, Centro de Regeneracion y Envejecimiento (CARE), Departamento de Biologia Celular y Molecular, MIFAB, Pontificia Universidad Catolica de Chile, Santiago (Chile); Brandan, Enrique, E-mail: ebrandan@bio.puc.cl [Centro de Regulacion Celular y Patologia, Centro de Regeneracion y Envejecimiento (CARE), Departamento de Biologia Celular y Molecular, MIFAB, Pontificia Universidad Catolica de Chile, Santiago (Chile)

2010-09-10

Skeletal muscle differentiation is strongly inhibited by transforming growth factor type {beta} (TGF-{beta}), although muscle formation as well as regeneration normally occurs in an environment rich in this growth factor. In this study, we evaluated the role of intracellular regulatory Smads proteins as well as TGF-{beta}-receptors (TGF-{beta}-Rs) during skeletal muscle differentiation. We found a decrease of TGF-{beta} signaling during differentiation. This phenomenon is explained by a decline in the levels of the regulatory proteins Smad-2, -3, and -4, a decrease in the phosphorylation of Smad-2 and lost of nuclear translocation of Smad-3 and -4 in response to TGF-{beta}. No change in the levels and inhibitory function of Smad-7 was observed. In contrast, we found that TGF-{beta}-R type I (TGF-{beta}-RI) and type II (TGF-{beta}-RII) increased on the cell surface during skeletal muscle differentiation. To analyze the direct role of the serine/threonine kinase activities of TGF-{beta}-Rs, we used the specific inhibitor SB 431542 and the dominant-negative form of TGF-{beta}-RII lacking the cytoplasmic domain. The TGF-{beta}-Rs were important for successful muscle formation, determined by the induction of myogenin, creatine kinase activity, and myosin. Silencing of Smad-2/3 expression by specific siRNA treatments accelerated myogenin, myosin expression, and myotube formation; although when SB 431542 was present inhibition in myosin induction and myotube formation was observed, suggesting that these last steps of skeletal muscle differentiation require active TGF-{beta}-Rs. These results suggest that both down-regulation of Smad regulatory proteins and cell signaling through the TGF-{beta} receptors independent of Smad proteins are essential for skeletal muscle differentiation.

Hot Flashes

Science.gov (United States)

Hot flashes Overview Hot flashes are sudden feelings of warmth, which are usually most intense over the face, neck and chest. Your skin might redden, as if you're blushing. Hot flashes can also cause sweating, and if you ...

TGF-β1-elevated TRPM7 channel regulates collagen expression in hepatic stellate cells via TGF-β1/Smad pathway

International Nuclear Information System (INIS)

Fang, Ling; Huang, Cheng; Meng, Xiaoming; Wu, Baoming; Ma, Taotao; Liu, Xuejiao; Zhu, Qian; Zhan, Shuxiang; Li, Jun

2014-01-01

Transdifferentiation of hepatic stellate cells (HSCs) into myofibroblasts plays a critical role in the development of liver fibrosis, since myofibroblasts are the key cells responsible for excessive deposition of ECM proteins. Transient receptor potential melastatin 7 (TRPM7), a non-selective cation channel with protein serine/threonine kinase activity, has been demonstrated to function in the proliferation of activated HSCs. Here, we investigated the functional role of TRPM7 in collagen deposition in activated HSC-T6 cells (a rat hepatic stellate cell line). TRPM7 mRNA and protein were measured by Real-time PCR and Western blot in TGF-β1-activated HSC-T6 cells in vitro. Results demonstrated that TRPM7 protein was dramatically increased in fibrotic human livers. Stimulation of HSC-T6 cells with TGF-β1 increased TRPM7 mRNA and protein level in a time-dependent manner. Nevertheless, TGF-β1-elicited upregulation of TRPM7 in HSC-T6 cells was abrogated by SB431542 (TGF-β1 receptor blocker) or SIS3 (inhibitor of Smad3 phosphorylation). Additionally, blockade of TRPM7 channels with non-specific TRPM7 blocker 2-APB or synthetic siRNA targeting TRPM7 attenuated TGF-β1-induced expression of myofibroblast markers, as measured by the induction of α-SMA and Col1α1. Silencing TRPM7 also increased the ratio of MMPs/TIMPs by increasing MMP-13 expression and decreasing TIMP-1 and TIMP-2 levels. Strikingly, phosphorylation of p-Smad2 and p-Smad3, associated with collagen production, was decreased in TRPM7 deficient HSC-T6 cells. These observations suggested that TGF-β1 elevates TRPM7 expression in HSCs via Smad3-dependant mechanisms, which in turn contributes Smad protein phosphorylation, and subsequently increases fibrous collagen expression. Therefore, TRPM7 may constitute a useful target for the treatment of liver fibrosis. - Highlights: • Upregulation of TRPM7 protein in human fibrotic livers • Upregulation of TRPM7 by TGF-β1 elicited Smad signaling in HSC-T6 cells

TGF-β1-elevated TRPM7 channel regulates collagen expression in hepatic stellate cells via TGF-β1/Smad pathway

Energy Technology Data Exchange (ETDEWEB)

Fang, Ling, E-mail: fangling_1984@126.com [School of Pharmacy, Anhui Medical University, Mei Shan Road, Hefei, Anhui Province 230032 (China); Institute for Liver Diseases of Anhui Medical University, Mei Shan Road, Hefei, Anhui Province 230032 (China); Key Laboratory of Anti-inflammatory and Immune Medicine, Anhui Medical University, Ministry of Education, Mei Shan Road, Hefei, Anhui Province 230032 (China); The First Affiliated Hospital of Anhui Medical University, Mei Shan Road, Hefei, Anhui Province 230032 (China); Huang, Cheng; Meng, Xiaoming; Wu, Baoming; Ma, Taotao; Liu, Xuejiao; Zhu, Qian [School of Pharmacy, Anhui Medical University, Mei Shan Road, Hefei, Anhui Province 230032 (China); Institute for Liver Diseases of Anhui Medical University, Mei Shan Road, Hefei, Anhui Province 230032 (China); Key Laboratory of Anti-inflammatory and Immune Medicine, Anhui Medical University, Ministry of Education, Mei Shan Road, Hefei, Anhui Province 230032 (China); Zhan, Shuxiang [School of Pharmacy, Anhui Medical University, Mei Shan Road, Hefei, Anhui Province 230032 (China); Institute for Liver Diseases of Anhui Medical University, Mei Shan Road, Hefei, Anhui Province 230032 (China); Key Laboratory of Anti-inflammatory and Immune Medicine, Anhui Medical University, Ministry of Education, Mei Shan Road, Hefei, Anhui Province 230032 (China); The First Affiliated Hospital of Anhui Medical University, Mei Shan Road, Hefei, Anhui Province 230032 (China); Li, Jun, E-mail: lj@ahmu.edu.cn [School of Pharmacy, Anhui Medical University, Mei Shan Road, Hefei, Anhui Province 230032 (China); Institute for Liver Diseases of Anhui Medical University, Mei Shan Road, Hefei, Anhui Province 230032 (China); Key Laboratory of Anti-inflammatory and Immune Medicine, Anhui Medical University, Ministry of Education, Mei Shan Road, Hefei, Anhui Province 230032 (China)

2014-10-15

Transdifferentiation of hepatic stellate cells (HSCs) into myofibroblasts plays a critical role in the development of liver fibrosis, since myofibroblasts are the key cells responsible for excessive deposition of ECM proteins. Transient receptor potential melastatin 7 (TRPM7), a non-selective cation channel with protein serine/threonine kinase activity, has been demonstrated to function in the proliferation of activated HSCs. Here, we investigated the functional role of TRPM7 in collagen deposition in activated HSC-T6 cells (a rat hepatic stellate cell line). TRPM7 mRNA and protein were measured by Real-time PCR and Western blot in TGF-β1-activated HSC-T6 cells in vitro. Results demonstrated that TRPM7 protein was dramatically increased in fibrotic human livers. Stimulation of HSC-T6 cells with TGF-β1 increased TRPM7 mRNA and protein level in a time-dependent manner. Nevertheless, TGF-β1-elicited upregulation of TRPM7 in HSC-T6 cells was abrogated by SB431542 (TGF-β1 receptor blocker) or SIS3 (inhibitor of Smad3 phosphorylation). Additionally, blockade of TRPM7 channels with non-specific TRPM7 blocker 2-APB or synthetic siRNA targeting TRPM7 attenuated TGF-β1-induced expression of myofibroblast markers, as measured by the induction of α-SMA and Col1α1. Silencing TRPM7 also increased the ratio of MMPs/TIMPs by increasing MMP-13 expression and decreasing TIMP-1 and TIMP-2 levels. Strikingly, phosphorylation of p-Smad2 and p-Smad3, associated with collagen production, was decreased in TRPM7 deficient HSC-T6 cells. These observations suggested that TGF-β1 elevates TRPM7 expression in HSCs via Smad3-dependant mechanisms, which in turn contributes Smad protein phosphorylation, and subsequently increases fibrous collagen expression. Therefore, TRPM7 may constitute a useful target for the treatment of liver fibrosis. - Highlights: • Upregulation of TRPM7 protein in human fibrotic livers • Upregulation of TRPM7 by TGF-β1 elicited Smad signaling in HSC-T6 cells

NELIOTA: First temperature measurement of lunar impact flashes

Science.gov (United States)

Bonanos, A. Z.; Avdellidou, C.; Liakos, A.; Xilouris, E. M.; Dapergolas, A.; Koschny, D.; Bellas-Velidis, I.; Boumis, P.; Charmandaris, V.; Fytsilis, A.; Maroussis, A.

2018-04-01

We report the first scientific results from the NELIOTA (NEO Lunar Impacts and Optical TrAnsients) project, which has recently begun lunar monitoring observations with the 1.2-m Kryoneri telescope. NELIOTA aims to detect faint impact flashes produced by near-Earth meteoroids and asteroids and thereby help constrain the size-frequency distribution of near-Earth objects in the decimeter to meter range. The NELIOTA setup, consisting of two fast-frame cameras observing simultaneously in the R and I bands, enables - for the first time - direct analytical calculation of the flash temperatures. We present the first ten flashes detected, for which we find temperatures in the range 1600 to 3100 K, in agreement with theoretical values. Two of these flashes were detected on multiple frames in both filters and therefore yield the first measurements of the temperature drop for lunar flashes. In addition, we compute the impactor masses, which range between 100 g and 50 kg.

Flash sintering of ceramic materials

Science.gov (United States)

Dancer, C. E. J.

2016-10-01

During flash sintering, ceramic materials can sinter to high density in a matter of seconds while subjected to electric field and elevated temperature. This process, which occurs at lower furnace temperatures and in shorter times than both conventional ceramic sintering and field-assisted methods such as spark plasma sintering, has the potential to radically reduce the power consumption required for the densification of ceramic materials. This paper reviews the experimental work on flash sintering methods carried out to date, and compares the properties of the materials obtained to those produced by conventional sintering. The flash sintering process is described for oxides of zirconium, yttrium, aluminium, tin, zinc, and titanium; silicon and boron carbide, zirconium diboride, materials for solid oxide fuel applications, ferroelectric materials, and composite materials. While experimental observations have been made on a wide range of materials, understanding of the underlying mechanisms responsible for the onset and latter stages of flash sintering is still elusive. Elements of the proposed theories to explain the observed behaviour include extensive Joule heating throughout the material causing thermal runaway, arrested by the current limitation in the power supply, and the formation of defect avalanches which rapidly and dramatically increase the sample conductivity. Undoubtedly, the flash sintering process is affected by the electric field strength, furnace temperature and current density limit, but also by microstructural features such as the presence of second phase particles or dopants and the particle size in the starting material. While further experimental work and modelling is still required to attain a full understanding capable of predicting the success of the flash sintering process in different materials, the technique non-etheless holds great potential for exceptional control of the ceramic sintering process.

TGF-b y un inhibidor específico de TGF-b regulan pericentrina B y MYH9 en células de glioma TGF-b and a specific TGF-b inhibitor regulate pericentrin B and MYH9 in glioma cell lines

Directory of Open Access Journals (Sweden)

Rich Jeremy N.

2006-07-01

Full Text Available Malignant gliomas are heterogeneous, highly invasive vascular tumours. The multifunctional cytokine, transforming growth factor-beta (TGF-P, is expressed by grade III/IV gliomas and promotes tumour angiogenesis, invasión and immune escape. It has been shown previously that a small TGF-P receptor type I (TGF-(3-RI molecule inhibitor (SB-431542 blocks TGF-(3-mediated signal transduction, induction of angiogenic factor expression and cellular motility. As glioma cell lines display differential sensitivity to TGF-P, it was expected that they would also be differentially impacted by disruption of TGF-P signalling. Differential in gel expression (DIGE analysis and mass spectrometry was used in this work for determining protein regulation effects of both TGF-P and SB-431542 on human glioma cell lines. It was found that pericentrin B and non muscle myosin were differentially expressed in fragments which likely resulted from protease activation by the tumour growth mechanism. These results suggest that both pericentrin B and non-muscle myosin might be potential glioma biomarkers. Key words: DIGE, proteomics, glioma, TGF-P, mass spectrometry, non muscle myosin, pericentrin B.Los gliomas malignos son tumores vasculares heterogéneos altamente invasivos. El factor de transformación de creci­miento P (TGF-P es una citoquina multifuncional que es expresada por gliomas de grado III /IV y promueve angiogenesis de tumores, invasión y escape inmunológico. Recientemente se demostró que una pequeña molécula inhibidora (SB-431542 del receptor de TGF-P tipo I (TGF-P-RI, bloquea la señal de transducción mediada por TGF-P, la inducción del factor angiogénico de expresión y la movilidad celular. Ya que las líneas celulares de gliomas mues­tran sensitividad diferencial a TGF-P, se esperaba que también mostrarían impacto diferencial por el bloqueo de la señal de TGF-p. En el presente trabajo se usó un análisis diferencial en gel (DIGE, por sus

TGF-b and a specific TGF-b inhibitor regulate pericentrin B and MYH9 in glioma cell lines

Directory of Open Access Journals (Sweden)

Óscar Álzate

2006-01-01

Full Text Available Malignant gliomas are heterogeneous, highly invasive vascular tumours. The multifunctional cytokine, transforming growth factor-beta (TGF-P, is expressed by grade III/IV gliomas and promotes tumour angiogenesis, invasión and immune escape. It has been shown previously that a small TGF-P receptor type I (TGF-(3-RI molecule inhibitor (SB-431542 blocks TGF-(3-mediated signal transduction, induction of angiogenic factor expression and cellular motility. As glioma cell lines display differential sensitivity to TGF-P, it was expected that they would also be differentially impacted by disruption of TGF-P signalling. Differential in gel expression (DIGE analysis and mass spectrometry was used in this work for determining protein regulation effects of both TGF-P and SB-431542 on human glioma cell lines. It was found that pericentrin B and non muscle myosin were differentially expressed in fragments which likely resulted from protease activation by the tumour growth mechanism. These results suggest that both pericentrin B and non-muscle myosin might be potential glioma biomarkers. Key words: DIGE, proteomics, glioma, TGF-P, mass spectrometry, non muscle myosin, pericentrin B.

TGF-β2 and TGF-β3 from cultured β-amyloid-treated or 3xTg-AD-derived astrocytes may mediate astrocyte-neuron communication.

Science.gov (United States)

Tapella, Laura; Cerruti, Matteo; Biocotino, Isabella; Stevano, Alessio; Rocchio, Francesca; Canonico, Pier Luigi; Grilli, Mariagrazia; Genazzani, Armando A; Lim, Dmitry

2018-02-01

Astrocytes participate in the development and resolution of neuroinflammation in numerous ways, including the release of cytokines and growth factors. Among many, astrocytes release transforming growth factors beta (TGF-β) TGF-β1, TGF-β2 and TGF-β3. TGF-β1 is the most studied isoform, while production and release of TGF-β2 and TGF-β3 by astrocytes have been poorly characterized. Here, we report that purified cultures of hippocampal astrocytes produce mainly TGF-β3 followed by TGF-β2 and TGF-β1. Furthermore, astrocytes release principally the active form of TGF-β3 over the other two. Changes in release of TGF-β were sensitive to the calcineurin (CaN) inhibitor FK506. Starvation had no effect on TGF-β1 and TGF-β3 while TGF-β2 mRNA was significantly up-regulated in a CaN-dependent manner. We further investigated production and release of astroglial TGF-β in Alzheimer's disease-related conditions. Oligomeric β-amyloid (Aβ) down-regulated TGF-β1, while up-regulating TGF-β2 and TGF-β3, in a CaN-dependent manner. In cultured hippocampal astrocytes from 3xTg-AD mice, TGF-β2 and TGF-β3, but not TGF-β1, were up-regulated, and this was CaN-independent. In hippocampal tissues from symptomatic 3xTg-AD mice, TGF-β2 was up-regulated with respect to control mice. Finally, treatment with recombinant TGF-βs showed that TGF-β2 and TGF-β3 significantly reduced PSD95 protein in cultured hippocampal neurons, and this effect was paralleled by conditioned media from Aβ-treated astrocytes or from astrocytes from 3xTg-AD mice. Taken together, our data suggest that TGF-β2 and TGF-β3 are produced by astrocytes in a CaN-dependent manner and should be investigated further in the context of astrocyte-mediated neurodegeneration. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Exogenous modulation of TGF-β1 influences TGF-βR-III-associated vascularization during wound healing in irradiated tissue

International Nuclear Information System (INIS)

Wehrhan, F.; Schultze-Mosgau, S.; Grabenbauer, G.G.; Roedel, F.; Amann, K.

2004-01-01

Background and purpose: Following preoperative radiotherapy prior to ablative surgery of squamous epithelial cell carcinomas of the head and neck region, wound-healing disorders occur. Previous experimental studies showed altered expression of transforming growth factor-(TGF-)β isoforms following surgery in irradiated graft beds. Altered levels of TGF-β 1 are reported to promote fibrosis and to suppress vascularization during wound healing, whereas expression of TGF-β receptor-III (TGF-βR-III) is associated with vascularization. The aim of the study was to analyze the influence of anti-TGF-β 1 treatment on TGF-βR-III-associated vascularization in the transition area between irradiated graft bed and graft. Material and methods: Wistar rats (male, weight 300-500 g) underwent preoperative irradiation of the head and neck region with 40 Gy (four fractions of 10 Gy each; n=16 animals). A free myocutaneous gracilis flap taken from the groin was then transplanted to the neck in all rats. The time interval between operation and transplantation was 4 weeks. Eight animals received 1 μg anti-TGF-β 1 into the graft bed by intradermal injection on days 1-7 after surgery. On days 3, 7, 14, 28, 56, and 120, skin samples were taken from the transition area between transplant and graft bed and from the graft bed itself. Immunohistochemistry was performed using the ABC-POX method to analyze the TGF-βR-III and E-selection expression. Histomorphometry was performed to analyze the percentage and the area of positively stained vessels. Results: A significantly higher expression of TGF-βR-III was seen in the irradiated and anti-TGF-β 1 -treated graft bed in comparison to the group receiving preoperative irradiation followed by transplantation alone. The percentage of TGF-βR-III positively staining capillaries from the total amount of capillaries in the anti-TGF-β 1 -treated graft bed was higher than in the group irradiated only. The total area of capillaries was also higher

Time-resolved dissection of early phosphoproteome and ensuing proteome changes in response to TGF-β

DEFF Research Database (Denmark)

J D'Souza, Rochelle C; Knittle, Anna M; Nagaraj, Nagarjuna

2014-01-01

and phosphorylation and knowledge of protein interactions and transcriptional regulation provided a comprehensive representation of the dynamic signaling events underlying TGF-β-induced changes in cell behavior. Our data suggest that in epithelial cells stimulated with TGF-β, early signaling is a mixture of both pro...... changes of cultured human keratinocytes undergoing EMT and cell cycle arrest in response to stimulation with TGF-β. We quantified significant changes in 2079 proteins and 2892 phosphorylation sites regulated by TGF-β. We identified several proteins known to be involved in TGF-β-induced cellular processes...... by phosphorylation of the transcriptional regulators of the SMAD family by the TGF-β receptor complex, we observed rapid kinetics of changes in protein phosphorylation, indicating that many responses were mediated through SMAD-independent TGF-β signaling. Combined analysis of changes in protein abundance...

An engineered transforming growth factor β (TGF-β) monomer that functions as a dominant negative to block TGF-β signaling

Energy Technology Data Exchange (ETDEWEB)

Kim, Sun Kyung; Barron, Lindsey; Hinck, Cynthia S.; Petrunak, Elyse M.; Cano, Kristin E.; Thangirala, Avinash; Iskra, Brian; Brothers, Molly; Vonberg, Machell; Leal, Belinda; Richter, Blair; Kodali, Ravindra; Taylor, Alexander B.; Du, Shoucheng; Barnes, Christopher O.; Sulea, Traian; Calero, Guillermo; Hart, P. John; Hart, Matthew J.; Demeler, Borries; Hinck, Andrew P. (Texas-HSC); (NRCC); (Pitt)

2017-02-22

The transforming growth factor β isoforms, TGF-β1, -β2, and -β3, are small secreted homodimeric signaling proteins with essential roles in regulating the adaptive immune system and maintaining the extracellular matrix. However, dysregulation of the TGF-β pathway is responsible for promoting the progression of several human diseases, including cancer and fibrosis. Despite the known importance of TGF-βs in promoting disease progression, no inhibitors have been approved for use in humans. Herein, we describe an engineered TGF-β monomer, lacking the heel helix, a structural motif essential for binding the TGF-β type I receptor (TβRI) but dispensable for binding the other receptor required for TGF-β signaling, the TGF-β type II receptor (TβRII), as an alternative therapeutic modality for blocking TGF-β signaling in humans. As shown through binding studies and crystallography, the engineered monomer retained the same overall structure of native TGF-β monomers and bound TβRII in an identical manner. Cell-based luciferase assays showed that the engineered monomer functioned as a dominant negative to inhibit TGF-β signaling with a Ki of 20–70 nM. Investigation of the mechanism showed that the high affinity of the engineered monomer for TβRII, coupled with its reduced ability to non-covalently dimerize and its inability to bind and recruit TβRI, enabled it to bind endogenous TβRII but prevented it from binding and recruiting TβRI to form a signaling complex. Such engineered monomers provide a new avenue to probe and manipulate TGF-β signaling and may inform similar modifications of other TGF-β family members.

Heterogeneous engineered cartilage growth results from gradients of media-supplemented active TGF-β and is ameliorated by the alternative supplementation of latent TGF-β.

Science.gov (United States)

Albro, Michael B; Nims, Robert J; Durney, Krista M; Cigan, Alexander D; Shim, Jay J; Vunjak-Novakovic, Gordana; Hung, Clark T; Ateshian, Gerard A

2016-01-01

Transforming growth factor beta (TGF-β) has become one of the most widely utilized mediators of engineered cartilage growth. It is typically exogenously supplemented in the culture medium in its active form, with the expectation that it will readily transport into tissue constructs through passive diffusion and influence cellular biosynthesis uniformly. The results of this investigation advance three novel concepts regarding the role of TGF-β in cartilage tissue engineering that have important implications for tissue development. First, through the experimental and computational analysis of TGF-β concentration distributions, we demonstrate that, contrary to conventional expectations, media-supplemented exogenous active TGF-β exhibits a pronounced concentration gradient in tissue constructs, resulting from a combination of high-affinity binding interactions and a high cellular internalization rate. These gradients are sustained throughout the entire culture duration, leading to highly heterogeneous tissue growth; biochemical and histological measurements support that while biochemical content is enhanced up to 4-fold at the construct periphery, enhancements are entirely absent beyond 1 mm from the construct surface. Second, construct-encapsulated chondrocytes continuously secrete large amounts of endogenous TGF-β in its latent form, a portion of which undergoes cell-mediated activation and enhances biosynthesis uniformly throughout the tissue. Finally, motivated by these prior insights, we demonstrate that the alternative supplementation of additional exogenous latent TGF-β enhances biosynthesis uniformly throughout tissue constructs, leading to enhanced but homogeneous tissue growth. This novel demonstration suggests that latent TGF-β supplementation may be utilized as an important tool for the translational engineering of large cartilage constructs that will be required to repair the large osteoarthritic defects observed clinically. Copyright © 2015

[Effects of exogenous TGF-β3 on the expression of endogenous TGF-β3 in hepatic stellate cell-T6 (HSC-T6)].

Science.gov (United States)

Li, Ying; Deng, Liang; Qian, Wei; Zhou, Jian-ning; Xu, Ke-shu

2011-11-01

To investigate the effects of exogenous TGF-β3 on the expression of endogenous TGF-b3 in hepatic stellate cell (HSC). HSCs were cultured and divided into two groups: TGF-β3 group and blank control group, the cells of TGF-β3 group were exposed to TGF-b3 (10 ng/ml), whereas the blank control group was not treated. The cells were incubated in the presence of exogenous TGF-β3 and then (1) were harvested at 0h, 1h, 2h, 4h, 12h, 24h, and real time PCR was performed to detect the mRNA expression of endogenous TGF-β3. (2) The cells were collected at 0h, 1h, 6h, 12h, and western-blot was used to detect the protein synthesis of endogenous TGF-β3 in HSC; (3) The cell culture supernatant was harvested at 0h, 1h, 2h, 4h, 8h, 14h, 24h, and ELISA was performed to measure the total protein of extracellular TGF-β3; HSCs were treated with TGF-β3 (10 ng/ml) for 2h. The cells were then incubated in serum-free medium and the cell culture supernatant was harvested at 2.25h, 2.5h, 3h, 4h, 6h, 10h and 14h. ELISA was used to detect the extracellular secret ion of endogenous TGF-β3 by HSCs. (1) Exogenous TGF-β3 treatment induced a marked increase in TGF-β3 mRNA expression. By 2h of exogenous TGF-β3 treatment, maximal TGF-β3 mRNA expression levels (2.796 ± 0.518) of 2.74 fold above control values (1.022 ± 0.038) was reached (P endogenous TGF-β3 was found between two groups. (P > 0.05); (3) The total expression level of TGF-β3 reached a peak [(18.931 ± 2.904) ng/ml] at 4h after TGF-β3 treatment (1.89-fold higher than basic TGF-β3 (10 ng/ml). After that, it slowly declined. The expression peak [(0.835 ± 0.027) ng/ml] induction of extracellular secreted TGF-β3 was at 3h (32.12-fold higher than control [(0.026 ± 0.022) ng/ml], (P Exogenous TGF-β3 could increase the expression of endogenous TGF-β3 mRNA and extracellular secreted TGF-β3 protein obviously.

Lunar Impact Flash Locations from NASA's Lunar Impact Monitoring Program

Science.gov (United States)

Moser, D. E.; Suggs, R. M.; Kupferschmidt, L.; Feldman, J.

2015-01-01

Meteoroids are small, natural bodies traveling through space, fragments from comets, asteroids, and impact debris from planets. Unlike the Earth, which has an atmosphere that slows, ablates, and disintegrates most meteoroids before they reach the ground, the Moon has little-to-no atmosphere to prevent meteoroids from impacting the lunar surface. Upon impact, the meteoroid's kinetic energy is partitioned into crater excavation, seismic wave production, and the generation of a debris plume. A flash of light associated with the plume is detectable by instruments on Earth. Following the initial observation of a probable Taurid impact flash on the Moon in November 2005,1 the NASA Meteoroid Environment Office (MEO) began a routine monitoring program to observe the Moon for meteoroid impact flashes in early 2006, resulting in the observation of over 330 impacts to date. The main objective of the MEO is to characterize the meteoroid environment for application to spacecraft engineering and operations. The Lunar Impact Monitoring Program provides information about the meteoroid flux in near-Earth space in a size range-tens of grams to a few kilograms-difficult to measure with statistical significance by other means. A bright impact flash detected by the program in March 2013 brought into focus the importance of determining the impact flash location. Prior to this time, the location was estimated to the nearest half-degree by visually comparing the impact imagery to maps of the Moon. Better accuracy was not needed because meteoroid flux calculations did not require high-accuracy impact locations. But such a bright event was thought to have produced a fresh crater detectable from lunar orbit by the NASA spacecraft Lunar Reconnaissance Orbiter (LRO). The idea of linking the observation of an impact flash with its crater was an appealing one, as it would validate NASA photometric calculations and crater scaling laws developed from hypervelocity gun testing. This idea was

Comparison of the light flash phenomena observed in space and in laboratory experiments

International Nuclear Information System (INIS)

McNulty, P.J.; Pease, V.P.; Bond, V.P.

1976-01-01

Astronauts on Apollo and Skylab missions have reported observing a variety of visual phenomena when their eyes were closed and adapted to darkness. These observations were studied under controlled conditions during a number of sessions on board Apollo and Skylab spacecraft and the data available to date on these so-called light flashes is in the form of descriptions of the phenomena and frequency of occurrence. Similar visual phenomena have been demonstrated in a number of laboratories by exposing the eyes of human subjects to beams of neutrons, alphas, pions, and protons. More than one physical mechanism is involved in the laboratory and space phenomena. No direct comparison of the laboratory and space observations has been made by observers who have experienced both. However, the range of visual phenomena observed in the laboratory is consistent with the Apollo and Skylab observations. Measured detection efficiencies can be used to estimate the frequencies with which various phenomena would be observed if the subject was exposed to cosmic rays in space

FLASH Interface; a GUI for managing runtime parameters in FLASH simulations

Science.gov (United States)

Walker, Christopher; Tzeferacos, Petros; Weide, Klaus; Lamb, Donald; Flocke, Norbert; Feister, Scott

2017-10-01

We present FLASH Interface, a novel graphical user interface (GUI) for managing runtime parameters in simulations performed with the FLASH code. FLASH Interface supports full text search of available parameters; provides descriptions of each parameter's role and function; allows for the filtering of parameters based on categories; performs input validation; and maintains all comments and non-parameter information already present in existing parameter files. The GUI can be used to edit existing parameter files or generate new ones. FLASH Interface is open source and was implemented with the Electron framework, making it available on Mac OSX, Windows, and Linux operating systems. The new interface lowers the entry barrier for new FLASH users and provides an easy-to-use tool for experienced FLASH simulators. U.S. Department of Energy (DOE), NNSA ASC/Alliances Center for Astrophysical Thermonuclear Flashes, U.S. DOE NNSA ASC through the Argonne Institute for Computing in Science, U.S. National Science Foundation.

Nanotopography follows force in TGF-β1 stimulated epithelium

International Nuclear Information System (INIS)

Thoelking, Gerold; Oberleithner, Hans; Riethmuller, Christoph; Reiss, Bjoern; Wegener, Joachim; Pavenstaedt, Hermann

2010-01-01

Inflammation and cellular fibrosis often imply an involvement of the cytokine TGF-β1. TGF-β1 induces epithelial-to-mesenchymal transdifferentiation (EMT), a term describing the loss of epithelium-specific function. Indicative for this process are an elongated cell shape parallel to stress fibre formation. Many signalling pathways of TGF-β1 have been discovered, but mechanical aspects have not yet been investigated. In this study, atomic force microscopy (AFM) was used to analyse surface topography and mechanical properties of EMT in proximal kidney tubule epithelium (NRK52E). Elongated cells, an increase of stress fibre formation and a loss of microvillus compatible structures were observed as characteristic signs of EMT. Furthermore, AFM could identify an increase in stiffness by 71% after six days of stimulation with TGF-β1. As a novel topographical phenomenon, nodular protrusions emerged at the cell-cell junctions. They occurred preferentially at sites where stress fibres cross the border. Since these nodular protrusions were sensitive to inhibitors of force generation, they can indicate intracellular tension. The results demonstrate a manifest impact of elevated tension on the cellular topography.

Flash Platform Examination

Science.gov (United States)

2011-03-01

than would be performed in software”[108]. Uro Tinic, one of the Flash player’s engineers, further clarifies exactly what Flash player 10 hardware...www.adobe.com/products/flashplayer/features/ (Access date: 28 Sep 2009). [109] Uro , T. What Does GPU Acceleration Mean? (online), http...133] Shorten, A. (2009), Design to Development: Flash Catalyst to Flash Builder, In Proceedings of Adobe Max 2009, Los Angeles, CA. 142 DRDC

Simulated CONUS Flash Flood Climatologies from Distributed Hydrologic Models

Science.gov (United States)

Flamig, Z.; Gourley, J. J.; Vergara, H. J.; Kirstetter, P. E.; Hong, Y.

2016-12-01

This study will describe a CONUS flash flood climatology created over the period from 2002 through 2011. The MRMS reanalysis precipitation dataset was used as forcing into the Ensemble Framework For Flash Flood Forecasting (EF5). This high resolution 1-sq km 5-minute dataset is ideal for simulating flash floods with a distributed hydrologic model. EF5 features multiple water balance components including SAC-SMA, CREST, and a hydrophobic model all coupled with kinematic wave routing. The EF5/SAC-SMA and EF5/CREST water balance schemes were used for the creation of dual flash flood climatologies based on the differing water balance principles. For the period from 2002 through 2011 the daily maximum streamflow, unit streamflow, and time of peak streamflow was stored along with the minimum soil moisture. These variables are used to describe the states of the soils right before a flash flood event and the peak streamflow that was simulated during the flash flood event. The results will be shown, compared and contrasted. The resulting model simulations will be verified on basins less than 1,000-sq km with USGS gauges to ensure the distributed hydrologic models are reliable. The results will also be compared spatially to Storm Data flash flood event observations to judge the degree of agreement between the simulated climatologies and observations.

Blockade of TGF-β 1 Signalling Inhibits Cardiac NADPH Oxidase Overactivity in Hypertensive Rats

Directory of Open Access Journals (Sweden)

José Luis Miguel-Carrasco

2012-01-01

Full Text Available NADPH oxidases constitute a major source of superoxide anion (⋅O2 - in hypertension. Several studies suggest an important role of NADPH oxidases in different effects mediated by TGF-β 1. In this study we show that chronic administration of P144, a peptide synthesized from type III TGF-β 1 receptor, significantly reduced the cardiac NADPH oxidase expression and activity as well as in the nitrotyrosine levels observed in control spontaneously hypertensive rats (V-SHR to levels similar to control normotensive Wistar Kyoto rats. In addition, P144 was also able to reduce the significant increases in the expression of collagen type I protein and mRNA observed in hearts from V-SHR. In addition, positive correlations between collagen expression, NADPH oxidase activity, and nitrotyrosine levels were found in all animals. Finally, TGF-β 1-stimulated Rat-2 exhibited significant increases in NADPH oxidase activity that was inhibited in the presence of P144. It could be concluded that the blockade of TGF-β 1 with P144 inhibited cardiac NADPH oxidase in SHR, thus adding new data to elucidate the involvement of this enzyme in the profibrotic actions of TGF-β 1.

CXXC5 suppresses hepatocellular carcinoma by promoting TGF-β-induced cell cycle arrest and apoptosis.

Science.gov (United States)

Yan, Xiaohua; Wu, Jingyi; Jiang, Quanlong; Cheng, Hao; Han, Jing-Dong J; Chen, Ye-Guang

2018-02-01

Evading TGF-β-mediated growth inhibition is often associated with tumorigenesis in liver, including hepatocellular carcinoma (HCC). To better understand the functions and the underlying molecular mechanisms of TGF-β in HCC initiation and progression, we carried out transcriptome sequencing (RNA-Seq) to identify the target genes of TGF-β. CXXC5, a member of the CXXC-type zinc finger domain-containing protein family, was identified as a novel TGF-β target gene in Hep3B HCC cells. Knockdown of CXXC5 attenuated the expression of a substantial portion of TGF-β target genes and ameliorated TGF-β-induced growth inhibition or apoptosis of Hep3B cells, suggesting that CXXC5 is required for TGF-β-mediated inhibition of HCC progression. Analysis of the TCGA database indicated that CXXC5 expression is reduced in the majority of HCC tissue samples in comparison to that in normal tissues. Furthermore, CXXC5 associates with the histone deacetylase HDAC1 and competes its interaction with Smad2/3, thereby abolishing the inhibitory effect of HDAC1 on TGF-β signaling. These observations together suggest that CXXC5 may act as a tumor suppressor by promoting TGF-β signaling via a positive feedback loop, and reveal a strategy for HCC to bypass TGF-β-mediated cytostasis by disrupting the positive feedback regulation. Our findings shed new light on TGF-β signaling regulation and demonstrate the function of CXXC5 in HCC development.

Modulation of type II TGF-β receptor degradation by integrin-linked kinase.

Science.gov (United States)

Vi, Linda; Boo, Stellar; Sayedyahossein, Samar; Singh, Randeep K; McLean, Sarah; Di Guglielmo, Gianni M; Dagnino, Lina

2015-03-01

Cutaneous responses to injury, infection, and tumor formation involve the activation of resident dermal fibroblasts and subsequent transition to myofibroblasts. The key for induction of myofibroblast differentiation is the activation of transforming growth factor-β (TGF-β) receptors and stimulation of integrins and their associated proteins, including integrin-linked kinase (ILK). Cross-talk processes between TGF-β and ILK are crucial for myofibroblast formation, as ILK-deficient dermal fibroblasts exhibit impaired responses to TGF-β receptor stimulation. We now show that ILK associates with type II TGF-β receptors (TβRII) in ligand- and receptor kinase activity-independent manners. In cells with targeted Ilk gene inactivation, cellular levels of TβRII are decreased, through mechanisms that involve enhanced ubiquitination and proteasomal degradation. Partitioning of TGF-β receptors into membrane has been linked to proteasome-dependent receptor degradation. We found that interfering with membrane raft formation in ILK-deficient cells restored TβRII levels and signaling. These observations support a model whereby ILK functions in fibroblasts to direct TβRII away from degradative pathways during their differentiation into myofibroblasts.

Model of UV flashes due to gigantic blue jets

International Nuclear Information System (INIS)

Milikh, G M; Shneider, M N

2008-01-01

Analysis of UV flashes observed by the UV detector on board the 'Tatiana' microsatellite suggests, based on their location, pulse width and energy of the source of the photons, that the flashes were generated by gigantic blue jets (GBJs). Presented in this paper is a numerical model of UV flashes due to a bunch of long streamers which form a leader, a prong such as that observed in a GBJ. Using a previously developed model of upward propagation of a long streamer in the exponential atmosphere the paper describes temporal evolution of the UV flux generated by a bunch of long streamers, in the given spectral range 300-400 nm used by the UV detector on board 'Tatiana'. The model is in agreement with the observations.

Targeting TGF-β Signaling by Antisense Oligonucleotide-mediated Knockdown of TGF-β Type I Receptor

Directory of Open Access Journals (Sweden)

Dwi U Kemaladewi

2014-01-01

Full Text Available Duchenne muscular dystrophy (DMD is caused by lack of functional dystrophin and results in progressive myofiber damage and degeneration. In addition, impaired muscle regeneration and fibrosis contribute to the progressive pathology of DMD. Importantly, transforming growth factor-β (TGF-β is implicated in DMD pathology and is known to stimulate fibrosis and inhibit muscle regeneration. In this study, we present a new strategy to target TGF-β signaling cascades by specifically inhibiting the expression of TGF-β type I receptor TGFBR1 (ALK5. Antisense oligonucleotides (AONs were designed to specifically induce exon skipping of mouse ALK5 transcripts. AON-induced exon skipping of ALK5 resulted in specific downregulation of full-length receptor transcripts in vitro in different cell types, repression of TGF-β activity, and enhanced C2C12 myoblast differentiation. To determine the effect of these AONs in dystrophic muscles, we performed intramuscular injections of ALK5 AONs in mdx mice, which resulted in a decrease in expression of fibrosis-related genes and upregulation of Myog expression compared to control AON-injected muscles. In summary, our study presents a novel method to target TGF-β signaling cascades with potential beneficial effects for DMD.

The Evolution and Structure of Extreme Optical Lightning Flashes.

Science.gov (United States)

Peterson, Michael; Rudlosky, Scott; Deierling, Wiebke

2017-12-27

This study documents the composition, morphology, and motion of extreme optical lightning flashes observed by the Lightning Imaging Sensor (LIS). The furthest separation of LIS events (groups) in any flash is 135 km (89 km), the flash with the largest footprint had an illuminated area of 10,604 km 2 , and the most dendritic flash has 234 visible branches. The longest-duration convective LIS flash lasted 28 s and is overgrouped and not physical. The longest-duration convective-to-stratiform propagating flash lasted 7.4 s, while the longest-duration entirely stratiform flash lasted 4.3 s. The longest series of nearly consecutive groups in time lasted 242 ms. The most radiant recorded LIS group (i.e., "superbolt") is 735 times more radiant than the average group. Factors that impact these optical measures of flash morphology and evolution are discussed. While it is apparent that LIS can record the horizontal development of the lightning channel in some cases, radiative transfer within the cloud limits the flash extent and level of detail measured from orbit. These analyses nonetheless suggest that lightning imagers such as LIS and Geostationary Lightning Mapper can complement ground-based lightning locating systems for studying physical lightning phenomena across large geospatial domains.

Nuclear receptor TLX inhibits TGF-β signaling in glioblastoma

International Nuclear Information System (INIS)

Johansson, Erik; Zhai, Qiwei; Zeng, Zhao-jun; Yoshida, Takeshi; Funa, Keiko

2016-01-01

TLX (also called NR2E1) is an orphan nuclear receptor that maintains stemness of neuronal stem cells. TLX is highly expressed in the most malignant form of glioma, glioblastoma multiforme (GBM), and is important for the proliferation and maintenance of the stem/progenitor cells of the tumor. Transforming Growth Factor-β (TGF-β) is a cytokine regulating many different cellular processes such as differentiation, migration, adhesion, cell death and proliferation. TGF-β has an important function in cancer where it can work as either a tumor suppressor or oncogene, depending on the cancer type and stage of tumor development. Since glioblastoma often have dysfunctional TGF-β signaling we wanted to find out if there is any interaction between TLX and TGF-β in glioblastoma cells. We demonstrate that knockdown of TLX enhances the canonical TGF-β signaling response in glioblastoma cell lines. TLX physically interacts with and stabilizes Smurf1, which can ubiquitinate and target TGF-β receptor II for degradation, whereas knockdown of TLX leads to stabilization of TGF-β receptor II, increased nuclear translocation of Smad2/3 and enhanced expression of TGF-β target genes. The interaction between TLX and TGF-β may play an important role in the regulation of proliferation and tumor-initiating properties of glioblastoma cells. - Highlights: • TLX knockdown enhances TGF-β dependent Smad signaling in glioblastoma cells • TLX knockdown increases the protein level of TGF-β receptor II. • TLX stabilizes and retains Smurf1 in the cytoplasm. • TLX enhances Smurf1-dependent ubiquitination and degradation of TGF-β receptor II.

Nuclear receptor TLX inhibits TGF-β signaling in glioblastoma

Energy Technology Data Exchange (ETDEWEB)

Johansson, Erik; Zhai, Qiwei [Sahlgrenska Cancer Center at the Sahlgrenska Academy, University of Gothenburg, Box 425, SE 405 30 Gothenburg (Sweden); Zeng, Zhao-jun [Sahlgrenska Cancer Center at the Sahlgrenska Academy, University of Gothenburg, Box 425, SE 405 30 Gothenburg (Sweden); Molecular Biology Research Center, School of Life Sciences, Central South University, 110, Xiangya Road, Changsha, Hunan 410078 (China); Yoshida, Takeshi [Sahlgrenska Cancer Center at the Sahlgrenska Academy, University of Gothenburg, Box 425, SE 405 30 Gothenburg (Sweden); Funa, Keiko, E-mail: keiko.funa@gu.se [Sahlgrenska Cancer Center at the Sahlgrenska Academy, University of Gothenburg, Box 425, SE 405 30 Gothenburg (Sweden)

2016-05-01

TLX (also called NR2E1) is an orphan nuclear receptor that maintains stemness of neuronal stem cells. TLX is highly expressed in the most malignant form of glioma, glioblastoma multiforme (GBM), and is important for the proliferation and maintenance of the stem/progenitor cells of the tumor. Transforming Growth Factor-β (TGF-β) is a cytokine regulating many different cellular processes such as differentiation, migration, adhesion, cell death and proliferation. TGF-β has an important function in cancer where it can work as either a tumor suppressor or oncogene, depending on the cancer type and stage of tumor development. Since glioblastoma often have dysfunctional TGF-β signaling we wanted to find out if there is any interaction between TLX and TGF-β in glioblastoma cells. We demonstrate that knockdown of TLX enhances the canonical TGF-β signaling response in glioblastoma cell lines. TLX physically interacts with and stabilizes Smurf1, which can ubiquitinate and target TGF-β receptor II for degradation, whereas knockdown of TLX leads to stabilization of TGF-β receptor II, increased nuclear translocation of Smad2/3 and enhanced expression of TGF-β target genes. The interaction between TLX and TGF-β may play an important role in the regulation of proliferation and tumor-initiating properties of glioblastoma cells. - Highlights: • TLX knockdown enhances TGF-β dependent Smad signaling in glioblastoma cells • TLX knockdown increases the protein level of TGF-β receptor II. • TLX stabilizes and retains Smurf1 in the cytoplasm. • TLX enhances Smurf1-dependent ubiquitination and degradation of TGF-β receptor II.

Comparison of the Effects of SMART Board Technology and Flash Card Instruction on Sight Word Recognition and Observational Learning

Science.gov (United States)

Mechling, Linda C.; Gast, David L.; Thompson, Kimberly L.

2009-01-01

This study compared the effectiveness of SMART Board, interactive whiteboard technology and traditional flash cards in teaching reading in a small-group instructional arrangement. Three students with moderate intellectual disabilities were taught to read grocery store aisle marker words under each condition. Observational learning (students…

A global flash flood forecasting system

Science.gov (United States)

Baugh, Calum; Pappenberger, Florian; Wetterhall, Fredrik; Hewson, Tim; Zsoter, Ervin

2016-04-01

The sudden and devastating nature of flash flood events means it is imperative to provide early warnings such as those derived from Numerical Weather Prediction (NWP) forecasts. Currently such systems exist on basin, national and continental scales in Europe, North America and Australia but rely on high resolution NWP forecasts or rainfall-radar nowcasting, neither of which have global coverage. To produce global flash flood forecasts this work investigates the possibility of using forecasts from a global NWP system. In particular we: (i) discuss how global NWP can be used for flash flood forecasting and discuss strengths and weaknesses; (ii) demonstrate how a robust evaluation can be performed given the rarity of the event; (iii) highlight the challenges and opportunities in communicating flash flood uncertainty to decision makers; and (iv) explore future developments which would significantly improve global flash flood forecasting. The proposed forecast system uses ensemble surface runoff forecasts from the ECMWF H-TESSEL land surface scheme. A flash flood index is generated using the ERIC (Enhanced Runoff Index based on Climatology) methodology [Raynaud et al., 2014]. This global methodology is applied to a series of flash floods across southern Europe. Results from the system are compared against warnings produced using the higher resolution COSMO-LEPS limited area model. The global system is evaluated by comparing forecasted warning locations against a flash flood database of media reports created in partnership with floodlist.com. To deal with the lack of objectivity in media reports we carefully assess the suitability of different skill scores and apply spatial uncertainty thresholds to the observations. To communicate the uncertainties of the flash flood system output we experiment with a dynamic region-growing algorithm. This automatically clusters regions of similar return period exceedence probabilities, thus presenting the at-risk areas at a spatial

Mutual regulation of TGF-β1, TβRII and ErbB receptors expression in human thyroid carcinomas

Energy Technology Data Exchange (ETDEWEB)

Mincione, Gabriella, E-mail: g.mincione@unich.it [Department of Experimental and Clinical Sciences, University ‘G. d' Annunzio of Chieti-Pescara, Chieti (Italy); Center of Excellence on Aging, Ce.S.I., ‘G. d' Annunzio’ University Foundation, Chieti (Italy); Tarantelli, Chiara [Department of Experimental and Clinical Sciences, University ‘G. d' Annunzio of Chieti-Pescara, Chieti (Italy); Vianale, Giovina [Department of Experimental and Clinical Sciences, University ‘G. d' Annunzio of Chieti-Pescara, Chieti (Italy); Center of Excellence on Aging, Ce.S.I., ‘G. d' Annunzio’ University Foundation, Chieti (Italy); Di Marcantonio, Maria Carmela [Department of Experimental and Clinical Sciences, University ‘G. d' Annunzio of Chieti-Pescara, Chieti (Italy); Cotellese, Roberto [Department of Experimental and Clinical Sciences, University ‘G. d' Annunzio of Chieti-Pescara, Chieti (Italy); Unit of General and Laparoscopic Surgery, SS Annunziata Hospital, Chieti (Italy); Francomano, Franco [Unit of General and Laparoscopic Surgery, SS Annunziata Hospital, Chieti (Italy); Di Nicola, Marta; Costantini, Erica [Department of Experimental and Clinical Sciences, University ‘G. d' Annunzio of Chieti-Pescara, Chieti (Italy); Cichella, Annadomenica [Unit of General and Laparoscopic Surgery, SS Annunziata Hospital, Chieti (Italy); Muraro, Raffaella [Department of Experimental and Clinical Sciences, University ‘G. d' Annunzio of Chieti-Pescara, Chieti (Italy); Center of Excellence on Aging, Ce.S.I., ‘G. d' Annunzio’ University Foundation, Chieti (Italy)

2014-09-10

The role of EGF and TGF-β1 in thyroid cancer is still not clearly defined. TGF-β1 inhibited the cellular growth and migration of follicular (FTC-133) and papillary (B-CPAP) thyroid carcinoma cell lines. Co-treatments of TGF-β1 and EGF inhibited proliferation in both cell lines, but displayed opposite effect on their migratory capability, leading to inhibition in B-CPAP and promotion in FTC-133 cells, by a MAPK-dependent mechanism. TGF-β1, TβRII and EGFR expressions were evaluated in benign and malignant thyroid tumors. Both positivity (51.7% and 60.0% and 80.0% in FA and PTC and FTC) and overexpression (60.0%, 77.7% and 75.0% in FA, PTC and FTC) of EGFR mRNA correlates with the aggressive tumor behavior. The moderate overexpression of TGF-β1 and TβRII mRNA in PTC tissues (61.5% and 62.5%, respectively), counteracted their high overexpression in FTC tissues (100% and 100%, respectively), while EGFR overexpression was similar in both carcinomas. Papillary carcinomas were positive to E-cadherin expression, while the follicular carcinomas lose E-cadherin staining. Our findings of TGF-β1/TβRII and EGFR overexpressions together with a loss of E-cadherin observed in human follicular thyroid carcinomas, and of increased migration ability MAPK-dependent after EGF/TGF-β1 treatments in the follicular thyroid carcinoma cell line, reinforced the hypothesis of a cross-talk between EGF and TGF-β1 systems in follicular thyroid carcinomas phenotype. - Highlights: • We reinforce the hypothesis of a cross talk between EGF and TGF-β1 in follicular thyroid carcinoma. • Increased migration MAPK-dependent is observed after EGF+TGF-β1 treatment in follicular thyroid carcinoma cells. • EGF and TGF-β1 caused opposite effect on the migratory ability in B-CPAP and in FTC-133 cells. • TGF-β1, TβRII and EGFR are overexpressed in follicular thyroid carcinoma.

Mutual regulation of TGF-β1, TβRII and ErbB receptors expression in human thyroid carcinomas

International Nuclear Information System (INIS)

Mincione, Gabriella; Tarantelli, Chiara; Vianale, Giovina; Di Marcantonio, Maria Carmela; Cotellese, Roberto; Francomano, Franco; Di Nicola, Marta; Costantini, Erica; Cichella, Annadomenica; Muraro, Raffaella

2014-01-01

The role of EGF and TGF-β1 in thyroid cancer is still not clearly defined. TGF-β1 inhibited the cellular growth and migration of follicular (FTC-133) and papillary (B-CPAP) thyroid carcinoma cell lines. Co-treatments of TGF-β1 and EGF inhibited proliferation in both cell lines, but displayed opposite effect on their migratory capability, leading to inhibition in B-CPAP and promotion in FTC-133 cells, by a MAPK-dependent mechanism. TGF-β1, TβRII and EGFR expressions were evaluated in benign and malignant thyroid tumors. Both positivity (51.7% and 60.0% and 80.0% in FA and PTC and FTC) and overexpression (60.0%, 77.7% and 75.0% in FA, PTC and FTC) of EGFR mRNA correlates with the aggressive tumor behavior. The moderate overexpression of TGF-β1 and TβRII mRNA in PTC tissues (61.5% and 62.5%, respectively), counteracted their high overexpression in FTC tissues (100% and 100%, respectively), while EGFR overexpression was similar in both carcinomas. Papillary carcinomas were positive to E-cadherin expression, while the follicular carcinomas lose E-cadherin staining. Our findings of TGF-β1/TβRII and EGFR overexpressions together with a loss of E-cadherin observed in human follicular thyroid carcinomas, and of increased migration ability MAPK-dependent after EGF/TGF-β1 treatments in the follicular thyroid carcinoma cell line, reinforced the hypothesis of a cross-talk between EGF and TGF-β1 systems in follicular thyroid carcinomas phenotype. - Highlights: • We reinforce the hypothesis of a cross talk between EGF and TGF-β1 in follicular thyroid carcinoma. • Increased migration MAPK-dependent is observed after EGF+TGF-β1 treatment in follicular thyroid carcinoma cells. • EGF and TGF-β1 caused opposite effect on the migratory ability in B-CPAP and in FTC-133 cells. • TGF-β1, TβRII and EGFR are overexpressed in follicular thyroid carcinoma

Flash x-radiography for material motion detection

International Nuclear Information System (INIS)

Choate, L.M.; Buckalew, W.H.; Posey, L.D.

1977-01-01

A significant part of the experimental program dealing with the behavior of prototypic LMFBR fuel pin bundles under mild to severe power transients is that of the observation of fuel/cladding/coolant motion. The feasibility of using electron beam flash x-radiography as a diagnostic tool for safety test facilities is presently under evaluation. A summary of the objectives and approach of the flash x-radiography program is presented

Physiologically assessed hot flashes and endothelial function among midlife women.

Science.gov (United States)

Thurston, Rebecca C; Chang, Yuefang; Barinas-Mitchell, Emma; Jennings, J Richard; von Känel, Roland; Landsittel, Doug P; Matthews, Karen A

2017-08-01

Hot flashes are experienced by most midlife women. Emerging data indicate that they may be associated with endothelial dysfunction. No studies have tested whether hot flashes are associated with endothelial function using physiologic measures of hot flashes. We tested whether physiologically assessed hot flashes were associated with poorer endothelial function. We also considered whether age modified associations. Two hundred seventy-two nonsmoking women reporting either daily hot flashes or no hot flashes, aged 40 to 60 years, and free of clinical cardiovascular disease, underwent ambulatory physiologic hot flash and diary hot flash monitoring; a blood draw; and ultrasound measurement of brachial artery flow-mediated dilation to assess endothelial function. Associations between hot flashes and flow-mediated dilation were tested in linear regression models controlling for lumen diameter, demographics, cardiovascular disease risk factors, and estradiol. In multivariable models incorporating cardiovascular disease risk factors, significant interactions by age (P hot flashes (beta [standard error] = -2.07 [0.79], P = 0.01), and more frequent physiologic hot flashes (for each hot flash: beta [standard error] = -0.10 [0.05], P = 0.03, multivariable) were associated with lower flow-mediated dilation. Associations were not accounted for by estradiol. Associations were not observed among the older women (age 54-60 years) or for self-reported hot flash frequency, severity, or bother. Among the younger women, hot flashes explained more variance in flow-mediated dilation than standard cardiovascular disease risk factors or estradiol. Among younger midlife women, frequent hot flashes were associated with poorer endothelial function and may provide information about women's vascular status beyond cardiovascular disease risk factors and estradiol.

Pro Android Flash

CERN Document Server

Chin, Stephen; Campesato, Oswald

2011-01-01

Did you know you can take your Flash skills beyond the browser, allowing you to make apps for Android, iOS and the BlackBerry Tablet OS? Build dynamic apps today starting with the easy-to-use Android smartphones and tablets. Then, take your app to other platforms without writing native code. Pro Android Flash is the definitive guide to building Flash and other rich Internet applications (RIAs) on the Android platform. It covers the most popular RIA frameworks for Android developers - Flash and Flex - and shows how to build rich, immersive user experiences on both Android smartphones and tablet

Flash!

Science.gov (United States)

Schilling, Govert

2002-04-01

About three times a day our sky flashes with a powerful pulse of gamma ray bursts (GRB), invisible to human eyes but not to astronomers' instruments. The sources of this intense radiation are likely to be emitting, within the span of seconds or minutes, more energy than the sun will in its entire 10 billion years of life. Where these bursts originate, and how they come to have such incredible energies, is a mystery scientists have been trying to solve for three decades. The phenomenon has resisted study -- the flashes come from random directions in space and vanish without trace -- until very recently. In what could be called a cinematic conflation of Flash Gordon and The Hunt for Red October, Govert Schilling's Flash!: The Hunt for the Biggest Explosions in the Universe describes the exciting and ever-changing field of GRB research. Based on interviews with leading scientists, Flash! provides an insider's account of the scientific challenges involved in unravelling the enigmatic nature of GRBs. A science writer who has followed the drama from the very start, Schilling describes the ambition and jealousy, collegiality and competition, triumph and tragedy, that exists among those who have embarked on this recherche. Govert Schilling is a Dutch science writer and astronomy publicist. He is a contributing editor of Sky and Telescope magazine, and regularly writes for the news sections of Science and New Scientist. Schilling is the astronomy writer for de Volkskrant, one of the largest national daily newspapers in The Netherlands, and frequently talks about the Universe on Dutch radio broadcasts. He is the author of more than twenty popular astronomy books, and hundreds of newspaper and magazine articles on astronomy.

The TETRA-II Experiment to Observe Terrestrial Gamma Flashes at Ground Level - Preliminary Results

Science.gov (United States)

Cherry, M. L.; Adams, C.; Al-Nussirat, S.; Bai, S.; Banadaki, Y.; Bitzer, P. M.; Hoffmann, J.; Khosravi, E.; Legault, M.; Orang, M.; Pleshinger, D. J.; Rodriguez, R.; Smith, D.; Trepanier, J. C.; Sunda-Meya, A.; Zimmer, N.

2017-12-01

An upgraded version of the TGF and Energetic Thunderstorm Rooftop Array (TETRA-II) consists of an array of BGO scintillators to detect bursts of gamma rays from thunderstorms at ground level in four separate locations: the campus of Louisiana State University in Baton Rouge, Louisiana; the campus of the University of Puerto Rico at Utuado, Puerto Rico; the Centro Nacional de Metrologia de Panama (CENAMEP) in Panama City, Panama; and the Severe Weather Institute and Radar & Lightning Laboratories in Huntsville, Alabama. The original TETRA-I array of NaI scintillators at Louisiana State University detected 37 millisecond-scale bursts of gamma rays at energies 50 keV-2 MeV associated with nearby (brief description of the TETRA-I observations, a description of TETRA-II, and preliminary results of the first events observed by TETRA-II will be presented including frequency and time history of events, spectral information, and correlation with local radar and radio data.

Curcumin and emodin down-regulate TGF-β signaling pathway in human cervical cancer cells.

Directory of Open Access Journals (Sweden)

Pooja Chandrakant Thacker

Full Text Available Cervical cancer is the major cause of cancer related deaths in women, especially in developing countries and Human Papilloma Virus infection in conjunction with multiple deregulated signaling pathways leads to cervical carcinogenesis. TGF-β signaling in later stages of cancer is known to induce epithelial to mesenchymal transition promoting tumor growth. Phytochemicals, curcumin and emodin, are effective as chemopreventive and chemotherapeutic compounds against several cancers including cervical cancer. The main objective of this work was to study the effect of curcumin and emodin on TGF-β signaling pathway and its functional relevance to growth, migration and invasion in two cervical cancer cell lines, SiHa and HeLa. Since TGF-β and Wnt/β-catenin signaling pathways are known to cross talk having common downstream targets, we analyzed the effect of TGF-β on β-catenin (an important player in Wnt/β-catenin signaling and also studied whether curcumin and emodin modulate them. We observed that curcumin and emodin effectively down regulate TGF-β signaling pathway by decreasing the expression of TGF-β Receptor II, P-Smad3 and Smad4, and also counterbalance the tumorigenic effects of TGF-β by inhibiting the TGF-β-induced migration and invasion. Expression of downstream effectors of TGF-β signaling pathway, cyclinD1, p21 and Pin1, was inhibited along with the down regulation of key mesenchymal markers (Snail and Slug upon curcumin and emodin treatment. Curcumin and emodin were also found to synergistically inhibit cell population and migration in SiHa and HeLa cells. Moreover, we found that TGF-β activates Wnt/β-catenin signaling pathway in HeLa cells, and curcumin and emodin down regulate the pathway by inhibiting β-catenin. Taken together our data provide a mechanistic basis for the use of curcumin and emodin in the treatment of cervical cancer.

Feedback regulation of TGF-β signaling.

Science.gov (United States)

Yan, Xiaohua; Xiong, Xiangyang; Chen, Ye-Guang

2018-01-01

Transforming growth factor beta (TGF-β) is a multi-functional polypeptide that plays a critical role in regulating a broad range of cellular functions and physiological processes. Signaling is initiated when TGF-β ligands bind to two types of cell membrane receptors with intrinsic Ser/Thr kinase activity and transmitted by the intracellular Smad proteins, which act as transcription factors to regulate gene expression in the nucleus. Although it is relatively simple and straight-forward, this TGF-β/Smad pathway is regulated by various feedback loops at different levels, including the ligand, the receptor, Smads and transcription, and is thus fine-tuned in terms of signaling robustness, duration, specificity, and plasticity. The precise control gives rise to versatile and context-dependent pathophysiological functions. In this review, we firstly give an overview of TGF-β signaling, and then discuss how each step of TGF-β signaling is finely controlled by distinct modes of feedback mechanisms, involving both protein regulators and miRNAs. © The Author 2017. Published by Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Nuclear receptor TLX inhibits TGF-β signaling in glioblastoma.

Science.gov (United States)

Johansson, Erik; Zhai, Qiwei; Zeng, Zhao-Jun; Yoshida, Takeshi; Funa, Keiko

2016-05-01

TLX (also called NR2E1) is an orphan nuclear receptor that maintains stemness of neuronal stem cells. TLX is highly expressed in the most malignant form of glioma, glioblastoma multiforme (GBM), and is important for the proliferation and maintenance of the stem/progenitor cells of the tumor. Transforming Growth Factor-β (TGF-β) is a cytokine regulating many different cellular processes such as differentiation, migration, adhesion, cell death and proliferation. TGF-β has an important function in cancer where it can work as either a tumor suppressor or oncogene, depending on the cancer type and stage of tumor development. Since glioblastoma often have dysfunctional TGF-β signaling we wanted to find out if there is any interaction between TLX and TGF-β in glioblastoma cells. We demonstrate that knockdown of TLX enhances the canonical TGF-β signaling response in glioblastoma cell lines. TLX physically interacts with and stabilizes Smurf1, which can ubiquitinate and target TGF-β receptor II for degradation, whereas knockdown of TLX leads to stabilization of TGF-β receptor II, increased nuclear translocation of Smad2/3 and enhanced expression of TGF-β target genes. The interaction between TLX and TGF-β may play an important role in the regulation of proliferation and tumor-initiating properties of glioblastoma cells. Copyright © 2016. Published by Elsevier Inc.

THE EFFECTS OF Jatropha curcas L SEED EXTRACT IN REGULATION EXPRESSION TUMOR MARKER OF TGF- β1 GENE

Directory of Open Access Journals (Sweden)

Endah Wulandari

2017-04-01

Full Text Available The role of TGF-β1 is known as the main immunosuppresor associated with tumor, but on the other opinion, it is associated with proliferation and tumor invasion. The increase and decrease of the secretion of TGF-β is to regulate the proliferation, differentiation, and death of various cell types. Now we all know the extract of Jatropha curcas L seed serves as antitumor. Allegedly, it can regulate the expression of TGF-β1 in control of cell number. The purpose of this study is to determine the effects of Jatropha seeds to the regulation of gene expression of TGF-β1 as a tumor marker. The method is performed by giving a dose groups the extract of jatropha seed (0, 5, 25, 50, 250 mg/BB in mice. Then measurement of mRNA expression (RT-PCR, the protein of TGF-β1 levels (ELISA, and qualitative observations of liver histology were done. The expression of TGF-β1 mRNA is significantly 4.39 to 7.34 times higher than (ANOVA, p 0.05 than the control. Histological observation of liver showed the extract of jatropha seed induces damage nucleus of hepatocytes cell and sinusoidal. The effects extract of jatropha seed increased the level of TGF-β1 mRNA but not followed by increasing protein of TGF-β1 levels, and it was stimulated necrosis and apoptosis of hepatocytes cell.

Professional Flash Lite Mobile Development

CERN Document Server

Anderson, J G

2010-01-01

Discover how to create Flash Lite mobile apps from the ground up. Adobe Flash is an ideal choice for developing rich interactive content for "Flash-enabled" mobile devices; and with this book, you'll learn how to create unique applications with Flash Lite. Through a series of code samples and extensive example applications, you'll explore the core concepts, key features, and best practices of the Flash Lite player. Coverage reveals various ways to develop Flash mobile content, create applications with a cross-platform programming framework based on the Model, View and Controller conc

Search Engine Optimization for Flash Best Practices for Using Flash on the Web

CERN Document Server

Perkins, Todd

2009-01-01

Search Engine Optimization for Flash dispels the myth that Flash-based websites won't show up in a web search by demonstrating exactly what you can do to make your site fully searchable -- no matter how much Flash it contains. You'll learn best practices for using HTML, CSS and JavaScript, as well as SWFObject, for building sites with Flash that will stand tall in search rankings.

TGF-β promotes glioma cell growth via activating Nodal expression through Smad and ERK1/2 pathways

International Nuclear Information System (INIS)

Sun, Jing; Liu, Su-zhi; Lin, Yan; Cao, Xiao-pan; Liu, Jia-ming

2014-01-01

Highlights: •TGF-β promoted Nodal expression in glioma cells. •TGF-β promoted Nodal expression via activating Smad and ERK1/2 pathways. •TGF-β promotes glioma cell growth via activating Nodal expression. -- Abstract: While there were certain studies focusing on the mechanism of TGF-β promoting the growth of glioma cells, the present work revealed another novel mechanism that TGF-β may promote glioma cell growth via enhancing Nodal expression. Our results showed that Nodal expression was significantly upregulated in glioma cells when TGF-β was added, whereas the TGF-β-induced Nodal expression was evidently inhibited by transfection Smad2 or Smad3 siRNAs, and the suppression was especially significant when the Smad3 was downregulated. Another, the attenuation of TGF-β-induced Nodal expression was observed with blockade of the ERK1/2 pathway also. Further detection of the proliferation, apoptosis, and invasion of glioma cells indicated that Nodal overexpression promoted the proliferation and invasion of tumor cells and inhibited their apoptosis, resembling the effect of TGF-β addition. Downregulation of Nodal expression via transfection Nodal-specific siRNA in the presence of TGF-β weakened the promoting effect of the latter on glioma cells growth, and transfecting Nodal siRNA alone in the absence of exogenous TGF-β more profoundly inhibited the growth of glioma cells. These results demonstrated that while both TGF-β and Nodal promoted glioma cells growth, the former might exert such effect by enhancing Nodal expression, which may form a new target for glioma therapy

The dynamics of TGF-β in dental pulp, odontoblasts and dentin.

Science.gov (United States)

Niwa, Takahiko; Yamakoshi, Yasuo; Yamazaki, Hajime; Karakida, Takeo; Chiba, Risako; Hu, Jan C-C; Nagano, Takatoshi; Yamamoto, Ryuji; Simmer, James P; Margolis, Henry C; Gomi, Kazuhiro

2018-03-13

Transforming growth factor-beta (TGF-β) is critical for cell proliferation and differentiation in dental pulp. Here, we show the dynamic mechanisms of TGF-β in porcine dental pulp, odontoblasts and dentin. The mRNA of latent TGF-β1 and TGF-β3 is predominantly expressed in odontoblasts, whereas the mRNA expression level of latent TGF-β2 is high in dental pulp. TGF-β1 is a major isoform of TGF-β, and latent TGF-β1, synthesized in dental pulp, is primarily activated by matrix metalloproteinase 11 (MMP11). Activated TGF-β1 enhances the mRNA expression levels of MMP20 and full-length dentin sialophosphoprotein (DSPP) in dental pulp cells, coinciding with the induction of odontoblast differentiation. Latent TGF-β1 synthesized in odontoblasts is primarily activated by MMP2 and MMP20 in both odontoblasts and dentin. The activity level of TGF-β1 was reduced in the dentin of MMP20 null mice, although the amount of latent TGF-β1 expression did not change between wild-type and MMP20 null mice. TGF-β1 activity was reduced with the degradation of DSPP-derived proteins that occurs with ageing. We propose that to exert its multiple biological functions, TGF-β1 is involved in a complicated dynamic interaction with matrix metalloproteinases (MMPs) and/or DSPP-derived proteins present in dental pulp, odontoblasts and dentin.

Multi-Level Bitmap Indexes for Flash Memory Storage

Energy Technology Data Exchange (ETDEWEB)

Wu, Kesheng; Madduri, Kamesh; Canon, Shane

2010-07-23

Due to their low access latency, high read speed, and power-efficient operation, flash memory storage devices are rapidly emerging as an attractive alternative to traditional magnetic storage devices. However, tests show that the most efficient indexing methods are not able to take advantage of the flash memory storage devices. In this paper, we present a set of multi-level bitmap indexes that can effectively take advantage of flash storage devices. These indexing methods use coarsely binned indexes to answer queries approximately, and then use finely binned indexes to refine the answers. Our new methods read significantly lower volumes of data at the expense of an increased disk access count, thus taking full advantage of the improved read speed and low access latency of flash devices. To demonstrate the advantage of these new indexes, we measure their performance on a number of storage systems using a standard data warehousing benchmark called the Set Query Benchmark. We observe that multi-level strategies on flash drives are up to 3 times faster than traditional indexing strategies on magnetic disk drives.

Stellate Cell Activation and Imbalanced Expression of TGF-β1/TGF-β3 in Acute Autoimmune Liver Lesions Induced by ConA in Mice

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Liyun Wang

2017-01-01

Full Text Available Objective. To study the pathogenic feature of liver injury, activation of hepatic stellate cells, and dynamic expression of TGF-β1/TGF-β3 to reveal their role in liver injury induced by ConA. Methods. Mice were randomly divided into control group and ConA treatment group. ConA (20 mg/kg was injected through vena caudalis in ConA treatment group; the controls received the same volume of saline injection. After injection for 2 h, 8 h, 24 h, and 48 h, animals were terminated. Blood, liver, and spleen were harvested. Liver function and histopathology were studied. α-SMA, vimentin, TGF-β1, and TGF-β3 were detected. Results. After ConA injection, liver damage started to increase. Expression of α-SMA, vimentin, TGF-β1, and TGF-β3 was significantly enhanced; all above indicators reached peak at 8 h; but from 24 h after ConA injection, TGF-β3 expression began to decline, while the TGF-β1/TGF-β3 ratio at 48 h was significantly lower than control. Conclusion. (1 Autoimmune liver injury induced by ConA showed time-based features, in which the most serious liver lesions happened at 8 h after ConA injection. (2 Early activation of HSC and imbalance expression of TGF-β1 and TGF-β3 existed in ConA-induced acute autoimmune liver injury, which may be associated with liver dysfunction and the mechanisms of progression to fibrosis.

Motorist actions at a crosswalk with an in-pavement flashing light system.

Science.gov (United States)

Karkee, Ganesh J; Nambisan, Shashi S; Pulugurtha, Srinivas S

2010-12-01

An in-pavement flashing light system is used at crosswalks to alert motorists and pedestrians of possible conflicts and to influence their behavior to enhance safety. The relative behaviors of the drivers and the pedestrians affect safety. An evaluation of motorist behavior at a pedestrian crosswalk with an in-pavement flashing light system is presented in this manuscript. Field observations provide the basis to evaluate motorist behavior at a crosswalk with an in-pavement flashing light system. Outcomes of pedestrian and motorists actions were observed to quantify measures of effectiveness (MOEs) such as yielding behavior of motorists, vehicle speeds, and yielding distance from the crosswalk. A before-and-after study design was used. The before condition was prior to the activation of the in-pavement flashing light system and the after condition was after the activation of the in-pavement flashing light system. The study was conducted on a relatively low-volume roadway located in the Henderson, Nevada. The significance of the differences in the MOEs between the 2 study periods was evaluated using statistical analysis tools such as a one-tailed test for proportions and the Welch-Satterthwaite t-test. The results show that the installation of the in-pavement flashing light system increased the yielding behavior of motorists significantly (P pavement flashing light system is seen to be effective to improve motorists' yielding behavior and the speeds of vehicles were also observed to decrease in the presence of pedestrians.

Spatial-temporal characteristics of lightning flash size in a supercell storm

Science.gov (United States)

Zhang, Zhixiao; Zheng, Dong; Zhang, Yijun; Lu, Gaopeng

2017-11-01

The flash sizes of a supercell storm, in New Mexico on October 5, 2004, are studied using the observations from the New Mexico Lightning Mapping Array and the Albuquerque, New Mexico, Doppler radar (KABX). First, during the temporal evolution of the supercell, the mean flash size is anti-correlated with the flash rate, following a unary power function, with a correlation coefficient of - 0.87. In addition, the mean flash size is linearly correlated with the area of reflectivity > 30 dBZ at 5 km normalized by the flash rate, with a correlation coefficient of 0.88. Second, in the horizontal, flash size increases along the direction from the region near the convection zone to the adjacent forward anvil. The region of minimum flash size usually corresponds to the region of maximum flash initiation and extent density. The horizontal correspondence between the mean flash size and the flash extent density can also be fitted by a unary power function, and the correlation coefficient is > 0.5 in 50% of the radar volume scans. Furthermore, the quality of fit is positively correlated to the convective intensity. Third, in the vertical direction, the height of the maximum flash initiation density is close to the height of maximum flash extent density, but corresponds to the height where the mean flash size is relatively small. In the discussion, the distribution of the small and dense charge regions when and where convection is vigorous in the storm, is deduced to be responsible for the relationship that flash size is temporally and spatially anti-correlated with flash rate and density, and the convective intensity.

TGF-β Signaling Is Necessary and Sufficient for Pharyngeal Arch Artery Angioblast Formation

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Maryline Abrial

2017-07-01

Full Text Available The pharyngeal arch arteries (PAAs are transient embryonic blood vessels that mature into critical segments of the aortic arch and its branches. Although defects in PAA development cause life-threating congenital cardiovascular defects, the molecular mechanisms that orchestrate PAA morphogenesis remain unclear. Through small-molecule screening in zebrafish, we identified TGF-β signaling as indispensable for PAA development. Specifically, chemical inhibition of the TGF-β type I receptor ALK5 impairs PAA development because nkx2.5+ PAA progenitor cells fail to differentiate into tie1+ angioblasts. Consistent with this observation, we documented a burst of ALK5-mediated Smad3 phosphorylation within PAA progenitors that foreshadows angioblast emergence. Remarkably, premature induction of TGF-β receptor activity stimulates precocious angioblast differentiation, thereby demonstrating the sufficiency of this pathway for initiating the PAA progenitor to angioblast transition. More broadly, these data uncover TGF-β as a rare signaling pathway that is necessary and sufficient for angioblast lineage commitment.

NAND flash memory technologies

CERN Document Server

Aritome, Seiichi

2016-01-01

This book discusses basic and advanced NAND flash memory technologies, including the principle of NAND flash, memory cell technologies, multi-bits cell technologies, scaling challenges of memory cell, reliability, and 3-dimensional cell as the future technology. Chapter 1 describes the background and early history of NAND flash. The basic device structures and operations are described in Chapter 2. Next, the author discusses the memory cell technologies focused on scaling in Chapter 3, and introduces the advanced operations for multi-level cells in Chapter 4. The physical limitations for scaling are examined in Chapter 5, and Chapter 6 describes the reliability of NAND flash memory. Chapter 7 examines 3-dimensional (3D) NAND flash memory cells and discusses the pros and cons in structure, process, operations, scalability, and performance. In Chapter 8, challenges of 3D NAND flash memory are dis ussed. Finally, in Chapter 9, the author summarizes and describes the prospect of technologies and market for the fu...

Expression of TGF-β in Fractures Fixed by Nitinol Swan-like Memory Compressive Connectors

Science.gov (United States)

Li, M.; Zhang, C. C.; Xu, S. G.; Fu, Q. G.

2011-07-01

In this article, the effect of internal fixation of a Nitinol swan-like memory compressive connector (SMC) on the temporal expression of transforming growth factor-β (TGF-β) at fracture sites is evaluated. Specimens were collected from 35 New Zealand rabbits modeled for bilateral humeral fracture fixed with either SMC or stainless dynamic compression plate (DCP). Five rabbits each were killed at day 1, 3, 7, 14, 21, 28, and 56. The local positive staining potency, positive area ratio, and positive index of TGF-β were measured using an immunohistochemistry approach (EnVision) in combination with a computerized image analysis system. TGF-β staining was seen in mesenchymal cells, osteoblasts, chondrocytes, and in the extracellular matrix of fractures fixed in both the SMC and the DCP samples without a significant difference in staining at both the early stages (days 1 and 3) and day 56. A higher TGF-β content was observed in the fractures fixed with SMC when compared to that of DCP from day 7 to 28. As a conclusion, TGF-β is highly expressed in fractures fixed with SMC during chondrogenesis stage and entochondrostosis stage. Finally, the mechanism of how SMC promoting synthesis and secretion of TGF-β in the process of fracture healing has been discussed.

Research of TGF-beta1 Inducing Lung Adencarcinoma PC9 Cells to Mesenchymal Cells Transition

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Xiaofeng CHEN

2010-01-01

Full Text Available Background and objective It has been proven that epithelial-mesenchymal transition (EMT not only correlated with embryonic development but also could promote tumor invasion and metastasis. Transforming growth factor beta-1 (TGF-β1 has been identified as the main inducer of tumor EMT. The aim of this study was to investigate the effects of TGF-β1 on EMT and PI3K/AKT signaling pathway in lung adencarcinoma PC9 cells. Methods Cultured PC9 cells were treated with different concentrations of TGF-β1 for 48 h. The morphological changes were observed under phase-contrast microscopy; EMT relative marker protein changes were assessed by Western blot and immunoflurescence staining. In addition, the expression of AKT and P-AKT were also measured by Western blot. Results The data showed that TGF-β1 could induce PC9 morphological alteration from epithelial to mesenchymal and upregulate the expression of mesenchymal maker protein Fibronectin. Obviously, the expression of P-AKT was downregulated by TGF-β1 treatment for 48 h. Conclusion TGF-β1 might induce EMT of PC9 cells , accompanied by the changes of PI3K/AKT signaling pathway.

Assessment of vulnerability to extreme flash floods in design storms.

Science.gov (United States)

Kim, Eung Seok; Choi, Hyun Il

2011-07-01

There has been an increase in the occurrence of sudden local flooding of great volume and short duration caused by heavy or excessive rainfall intensity over a small area, which presents the greatest potential danger threat to the natural environment, human life, public health and property, etc. Such flash floods have rapid runoff and debris flow that rises quickly with little or no advance warning to prevent flood damage. This study develops a flash flood index through the average of the same scale relative severity factors quantifying characteristics of hydrographs generated from a rainfall-runoff model for the long-term observed rainfall data in a small ungauged study basin, and presents regression equations between rainfall characteristics and the flash flood index. The aim of this study is to develop flash flood index-duration-frequency relation curves by combining the rainfall intensity-duration-frequency relation and the flash flood index from probability rainfall data in order to evaluate vulnerability to extreme flash floods in design storms. This study is an initial effort to quantify the flash flood severity of design storms for both existing and planned flood control facilities to cope with residual flood risks due to extreme flash floods that have ocurred frequently in recent years.

Automated Studies of Continuing Current in Lightning Flashes

Science.gov (United States)

Martinez-Claros, Jose

Continuing current (CC) is a continuous luminosity in the lightning channel that lasts longer than 10 ms following a lightning return stroke to ground. Lightning flashes following CC are associated with direct damage to power lines and are thought to be responsible for causing lightning-induced forest fires. The development of an algorithm that automates continuing current detection by combining NLDN (National Lightning Detection Network) and LEFA (Langmuir Electric Field Array) datasets for CG flashes will be discussed. The algorithm was applied to thousands of cloud-to-ground (CG) flashes within 40 km of Langmuir Lab, New Mexico measured during the 2013 monsoon season. It counts the number of flashes in a single minute of data and the number of return strokes of an individual lightning flash; records the time and location of each return stroke; performs peak analysis on E-field data, and uses the slope of interstroke interval (ISI) E-field data fits to recognize whether continuing current (CC) exists within the interval. Following CC detection, duration and magnitude are measured. The longest observed C in 5588 flashes was 631 ms. The performance of the algorithm (vs. human judgement) was checked on 100 flashes. At best, the reported algorithm is "correct" 80% of the time, where correct means that multiple stations agree with each other and with a human on both the presence and duration of CC. Of the 100 flashes that were validated against human judgement, 62% were hybrid. Automated analysis detects the first but misses the second return stroke in many cases where the second return stroke is followed by long CC. This problem is also present in human interpretation of field change records.

Gamma ray flashes add to mystery of upper atmosphere

Science.gov (United States)

Atmospheric electricity research has come a long way since Benjamin Franklin's kite-flying days. But what researchers have been learning lately about above-thunderstorm electricity has wrought a whole new era of mysteries.For a start, last summer a Colorado meteorologist sparked interest in a terrestrial phenomenon that the community first observed more than 100 years ago: optical flashes that occur above thunderstorms—at least 30 km above Earth. Walter Lyons with the Ft. Collins-based Mission Research Corporation, demonstrated that such flashes are not anomalies, as conventional scientific wisdom had held. He filmed hundreds of flashes during a 2-week period.

TGF-β Signaling Regulates Pancreatic β-Cell Proliferation through Control of Cell Cycle Regulator p27 Expression

International Nuclear Information System (INIS)

Suzuki, Tomoyuki; Dai, Ping; Hatakeyama, Tomoya; Harada, Yoshinori; Tanaka, Hideo; Yoshimura, Norio; Takamatsu, Tetsuro

2013-01-01

Proliferation of pancreatic β-cells is an important mechanism underlying β-cell mass adaptation to metabolic demands. Increasing β-cell mass by regeneration may ameliorate or correct both type 1 and type 2 diabetes, which both result from inadequate production of insulin by β-cells of the pancreatic islet. Transforming growth factor β (TGF-β) signaling is essential for fetal development and growth of pancreatic islets. In this study, we exposed HIT-T15, a clonal pancreatic β-cell line, to TGF-β signaling. We found that inhibition of TGF-β signaling promotes proliferation of the cells significantly, while TGF-β signaling stimulation inhibits proliferation of the cells remarkably. We confirmed that this proliferative regulation by TGF-β signaling is due to the changed expression of the cell cycle regulator p27. Furthermore, we demonstrated that there is no observed effect on transcriptional activity of p27 by TGF-β signaling. Our data show that TGF-β signaling mediates the cell-cycle progression of pancreatic β-cells by regulating the nuclear localization of CDK inhibitor, p27. Inhibition of TGF-β signaling reduces the nuclear accumulation of p27, and as a result this inhibition promotes proliferation of β-cells

Flash grundkursus

DEFF Research Database (Denmark)

Jensen, Henrik

2008-01-01

Flash er et programmeringssprog  og kan som sådant ikke noget i sig selv. Kursets mål er, at give den studerende et grundlæggende kendskab til Flash, så det kan bruges til præsentationer på skærm og til produktion af hjemmesider. På kurset arbejdes der med billede, grafik, lyd, video og interakti...

Age-Dependent Decrease in Serum Transforming Growth Factor (TGF-Beta 1 in Healthy Japanese Individuals; Population Study of Serum TGF-Beta 1 Level in Japanese

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Yoshihiro Okamoto

2005-01-01

Full Text Available Transforming growth factor-beta1 (TGF-β1, a multi-functional cytokine, is involved in regulating a variety of cellular activities and the serum/plasma TGF-β1 level is altered with various diseases. However, most published reports have described adult patients, and so we investigated the clinical significance of serum TGF-β1 level in pediatric patients. The diagnostic application of the measurement of serum TGF-β1 level depends critically on the control value, however, there is no information on the control value of serum TGF-β1 for children.

Expression of TGF-β3 in Isolated Fibroblasts from Foreskin

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Mahnaz Mahmoudi Rad

2015-05-01

Full Text Available Background: The multifunctional transforming growth factor beta (TGF-β is a glycoprotein that exists in three isoforms. TGF-β3 expression increases in fetal wound healing and reduces fibronectin and collagen I and III deposition, and also improves the architecture of the neodermis which is a combination of blood vessels and connective tissue during wound healing. Fibroblasts are key cells in the wound healing process. TGF-β3 plays a critical role in scar-free wound healing and fibroblast actions in the wound healing process. The aim of this study was to express the TGF-β3 gene (tgf-b3 in human foreskin fibroblasts (HFF’s. Methods: We obtained HFF’s from a newborn and a primary fibroblast culture was prepared. The cells were transfected with TGF-β3-pCMV6-XL5 plasmid DNA by both lipofection and electroporation. Expression of TGF-β3 was measured by enzyme-linked immunosorbent assay (ELISA. Results: The highest TGF-β3 expression (8.3-fold greater than control was obtained by lipofection after 72 hours using 3 μl of transfection reagent. Expression was 1.4-fold greater than control by electroporation. Conclusions: In this study, we successfully increased TGF-β3 expression in primary fibroblast cells. In the future, grafting these transfected fibroblasts onto wounds can help the healing process without scarring.

Ethanol Enhances TGF-β Activity by Recruiting TGF-β Receptors From Intracellular Vesicles/Lipid Rafts/Caveolae to Non-Lipid Raft Microdomains.

Science.gov (United States)

Huang, Shuan Shian; Chen, Chun-Lin; Huang, Franklin W; Johnson, Frank E; Huang, Jung San

2016-04-01

Regular consumption of moderate amounts of ethanol has important health benefits on atherosclerotic cardiovascular disease (ASCVD). Overindulgence can cause many diseases, particularly alcoholic liver disease (ALD). The mechanisms by which ethanol causes both beneficial and harmful effects on human health are poorly understood. Here we demonstrate that ethanol enhances TGF-β-stimulated luciferase activity with a maximum of 0.5-1% (v/v) in Mv1Lu cells stably expressing a luciferase reporter gene containing Smad2-dependent elements. In Mv1Lu cells, 0.5% ethanol increases the level of P-Smad2, a canonical TGF-β signaling sensor, by ∼ 2-3-fold. Ethanol (0.5%) increases cell-surface expression of the type II TGF-β receptor (TβR-II) by ∼ 2-3-fold from its intracellular pool, as determined by I(125) -TGF-β-cross-linking/Western blot analysis. Sucrose density gradient ultracentrifugation and indirect immunofluorescence staining analyses reveal that ethanol (0.5% and 1%) also displaces cell-surface TβR-I and TβR-II from lipid rafts/caveolae and facilitates translocation of these receptors to non-lipid raft microdomains where canonical signaling occurs. These results suggest that ethanol enhances canonical TGF-β signaling by increasing non-lipid raft microdomain localization of the TGF-β receptors. Since TGF-β plays a protective role in ASCVD but can also cause ALD, the TGF-β enhancer activity of ethanol at low and high doses appears to be responsible for both beneficial and harmful effects. Ethanol also disrupts the location of lipid raft/caveolae of other membrane proteins (e.g., neurotransmitter, growth factor/cytokine, and G protein-coupled receptors) which utilize lipid rafts/caveolae as signaling platforms. Displacement of these membrane proteins induced by ethanol may result in a variety of pathologies in nerve, heart and other tissues. © 2015 Wiley Periodicals, Inc.

TGF-β/Smad signaling in renal fibrosis

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Xiao-Ming eMeng

2015-03-01

Full Text Available TGF-β (transforming growth factor-β is well identified as a central mediator in renal fibrosis. TGF-β initiates canonical and non-canonical pathways to exert multiple biological effects. Among them, Smad signaling is recognized as a major pathway of TGF- signaling in progressive renal fibrosis. During fibrogenesis, Smad3 is highly activated, which is associated with the down-regulation of an inhibitory Smad7 via an ubiquitin E3-ligases-dependent degradation mechanism. The equilibrium shift between Smad3 and Smad7 leads to accumulation and activation of myofibroblasts, overproduction of ECM (extracellular matrix, and reduction in ECM degradation in the diseased kidney. Therefore, overexpression of Smad7 has been shown to be a therapeutic agent for renal fibrosis in various models of kidney diseases. In contrast, another downstream effecter of TGF-β/Smad signaling pathway, Smad2, exerts its renal protective role by counter-regulating the Smad3. Furthermore, recent studies demonstrated that Smad3 mediates renal fibrosis by down-regulating miR-29 and miR-200 but up-regulating miR-21 and miR-192. Thus, overexpression of miR-29 and miR-200 or down-regulation of miR-21 and miR-192 is capable of attenuating Smad3-mediated renal fibrosis in various mouse models of chronic kidney diseases. Taken together, TGF-/Smad signaling plays an important role in renal fibrosis. Targeting TGF-β/Smad3 signaling may represent a specific and effective therapy for chronic kidney diseases associated with renal fibrosis.

A Specific Inhibitor of TGF-β Receptor Kinase, SB-431542, as a Potent Antitumor Agent for Human Cancers

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Sunil K. Halder

2005-05-01

Full Text Available Small molecule inhibitors of signaling pathways have proven to be extremely useful for the development of therapeutic strategies for human cancers. Blocking the tumor-promoting effects of transforming growth factor-β (TGF-β in advanced stage carcinogenesis provides a potentially interesting drug target for therapeutic intervention. Although very few TGF-β receptor kinase inhibitors (TRKI are now emerging in preclinical studies, nothing is known about how these inhibitors might regulate the tumor-suppressive or tumor-promoting effects of TGF-β, or when these inhibitors might be useful for treatment during cancer progression. We have investigated the potential of TRKI in new therapeutic approaches in preclinical models. Here, we demonstrate that the TRKI, SB-431542, inhibits TGF-β-induced transcription, gene expression, apoptosis, and growth suppression. We have observed that SB-431542 attenuates the tumor-promoting effects of TGF-β, including TGF-β-induced EMT, cell motility, migration and invasion, and vascular endothelial growth factor secretion in human cancer cell lines. Interestingly, SB-431542 induces anchorage independent growth of cells that are growth-inhibited by TGF-β, whereas it reduces colony formation by cells that are growth-promoted by TGF-β. However, SB-431542 has no effect on a cell line that failed to respond to TGF-β. This represents a novel potential application of these inhibitors as therapeutic agents for human cancers with the goal of blocking tumor invasion, angiogenesis, and metastasis, when tumors are refractory to TGF-β-induced tumor-suppressor functions but responsive to tumor-promoting effects of TGF-β.

Impact of agricultural management on pluvial flash floods - Case study of an extreme event observed in Austria in 2016

Science.gov (United States)

Lumassegger, Simon; Achleitner, Stefan; Kohl, Bernhard

2017-04-01

Central Europe was affected by extreme flash floods in summer 2016 triggered by short, high-intensity storm cells. Besides fluvial runoff, local pluvial floods appear to increase recently. In frame of the research project SAFFER-CC (sensitivity assessment of critical condition for local flash floods - evaluating the recurrence under climate change) surface runoff and pluvial flooding is assessed using a coupled hydrological/2D hydrodynamic model for the severely affected municipality of Schwertberg, Upper Austria. In this small catchment several flooding events occurred in the last years, where the most severe event occurred during summer 2016. Several areas could only be reached after the flood wave subsided with observed flood marks up to one meter. The modeled catchment is intensively cultivated with maize, sugar beets, winter wheat and soy on the hillside and hence highly vulnerable to water erosion. The average inclination is relatively steep with 15 % leading to high flow velocities of surface runoff associated with large amounts of transported sediments. To assess the influence of land use and soil conservation on flash floods, field experiments with a portable irrigation spray installation were carried out at different locations. The test plots were subjected to rainfall with constant intensity of 100 mm/h for one hour. Consecutively a super intense, one hour lasting, rainfall hydrograph was applied after 30 minutes at the same plots, ranging from 50 mm/h to 200 mm/h. Surface runoff was collected and measured in a tank and water samples were taken to determine the suspended material load. Large differences of runoff coefficients were determined depending on the agricultural management. The largest discharge was measured in a maize field, where surface runoff occurred immediately after start of irrigation. The determined runoff coefficients ranged from 0.22 for soy up to 0.65 for maize for the same soil type and inclination. The conclusion that runoff is

Learning Flash CS4 Professional

CERN Document Server

Shupe, Rich

2009-01-01

Learning Flash CS4 Professional offers beginners and intermediate Flash developers a unique introduction to the latest version of Adobe's powerful multimedia application. This easy-to-read book is loaded with full-color examples and hands-on tasks to help you master Flash CS4's new motion editor, integrated 3D system, and character control using the new inverse kinematics bones animation system. No previous Flash experience is necessary.

RURAL FLASH-FLOOD BEHAVIOR IN GOUYAVE WATERSHED, GRENADA, CARIBBEAN ISLAND

Directory of Open Access Journals (Sweden)

Rahmat Aris Pratomo

2016-10-01

Full Text Available Flash-flood is considered as one of the most common natural disasters in Grenada, a tropical small state island in Caribbean Island. Grenada has several areas which are susceptible to flooding. One of them is Gouyave town which is located in the north-west of Grenada. Its land-use types are highly dominated by green areas, especially in the upper-part of the region. The built-up areas can only be found in the lower-part of Gouyave watershed, near the coastal area. However, there were many land conversions from natural land-use types into built-up areas in the upper-part region. They affected the decrease of water infiltration and the increase of potential run-off, making these areas susceptible to flash-flood. In addition, it is also influenced by the phenomenon of climate change. Changes in extreme temperature increase higher potential of hurricanes or wind-storm, directly related to the potential escalation of flash-flood. To develop effective mitigation strategies, understanding the behavior of flash-flood is required. The purpose of this paper was to observe the behavior of flash-flood in Gouyave watershed in various return periods using OpenLISEM software. It was used to develop and analyse the flash-flood characteristics. The result showed that the climatic condition (rainfall intensity and land-use are influential to the flash-flood event. Flash-flood occurs in 35 and 100 years return period. Flash-flood inundates Gouyave’s area in long duration, with below 1 m flood depth. The flood propagation time is slow. This condition is also influenced by the narrower and longer of Gouyave basin shape. To develop flash-flood reduction strategies, the overall understanding of flash-flood behavior is important. If the mitigation strategy is adapted to their behavior, the implementation will be more optimum.

Effects of electromagnetic radiation on morphology and TGF-β3 expression in mouse testicular tissue.

Science.gov (United States)

Luo, Yaning; Wang, Xiaowu; Chen, Yongbin; Xu, Shenglong; Ding, Guirong; Shi, Changhong

2013-08-09

Exposure to electromagnetic pulses in certain doses may lead to increase in the permeability of the blood testes barrier (BTB) in mice, which in turn affects spermatogenesis, penetration and spermiation. TGF-β3 is a key molecule involved in BTB permeability via regulation of tight junction proteins, and it participates in regulating spermatogenesis, synthesis of steroids and production of the extracellular matrix in testicular tissue. Therefore, it is hypothesized that TGF-β3 plays important roles in electromagnetic pulse (EMP)-induced changes in BTB permeability. In the present study, we carried out whole-body irradiation on mice using EMP of different intensities. No obvious pathological changes or significant increase in apoptosis was detected in testicular tissues after exposure to 100 and 200 pulses of intensity 200kV/m; however, with 400 pulses we observed the degeneration and shrinkage of testicular tissues along with a significant increase in apoptotic rate. Moreover, in the 100- and 200-EMP groups, a non-significant increase in TGF-β3 mRNA and protein expression was observed, whereas in the 400-EMP group a significant increase was observed (P<0.05). These results indicate that increase in the apoptotic rate of testicular tissues and increase in TGF-β3 expression may be one of the mechanisms for EMP-induced increase in BTB permeability in mice. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Flashing oscillation in pool water

International Nuclear Information System (INIS)

Takamasa, Tomoji; Kondo, Koichi; Hazuku, Tatsuya

1996-01-01

This paper presents an experimental study of high-pressure saturated water discharging into the pool water. The purpose of the experiment is to clarify the phenomena that occur in blow-down of high-pressure saturated water from the pressure vessel into the water-filled containment in the case of a wall-crack accident or a LOCA in an advanced reactor. The results revealed that a flashing oscillation (FO) occurs when high-pressure saturated water discharges into the pool water, under specified experimental settings. The range of the flashing oscillates between a point very close to and some distance from the vent hole. The pressures in the vent tube and pool water vary according to the flashing oscillation. The pressure oscillation and frequency of flashing position might be caused by the balancing action between the supply of saturated water, flashing at the control volume and its condensation on the steam-water interface. A linear analysis was conducted using a spherical flashing bubble model. The period of the flashing oscillation in the experiments can be explained by theoretical analysis

Hot flashes and sleep in women.

Science.gov (United States)

Moe, Karen E

2004-12-01

Sleep disturbances during menopause are often attributed to nocturnal hot flashes and 'sweats' associated with changing hormone patterns. This paper is a comprehensive critical review of the research on the relationship between sleep disturbance and hot flashes in women. Numerous studies have found a relationship between self-reported hot flashes and sleep complaints. However, hot flash studies using objective sleep assessment techniques such as polysomnography, actigraphy, or quantitative analysis of the sleep EEG are surprisingly scarce and have yielded somewhat mixed results. Much of this limited evidence suggests that hot flashes are associated with objectively identified sleep disruption in at least some women. At least some of the negative data may be due to methodological issues such as reliance upon problematic self-reports of nocturnal hot flashes and a lack of concurrent measures of hot flashes and sleep. The recent development of a reliable and non-intrusive method for objectively identifying hot flashes during the night should help address the need for substantial additional research in this area. Several areas of clinical relevance are described, including the effects of discontinuing combined hormone therapy (estrogen plus progesterone) or estrogen-only therapy, the possibility of hot flashes continuing for many years after menopause, and the link between hot flashes and depression.

MR colonography with fecal tagging: comparison between 2D turbo FLASH and 3D FLASH sequences

International Nuclear Information System (INIS)

Papanikolaou, Nickolas; Grammatikakis, John; Maris, Thomas; Prassopoulos, Panos; Gourtsoyiannis, Nicholas; Lauenstein, Thomas

2003-01-01

The objective of this study was to compare inversion recovery turbo 2D fast low-angle shot (FLASH) and 3D FLASH sequences for fecal-tagged MR colonography studies. Fifteen consecutive patients with indications for colonoscopy underwent MR colonography with fecal tagging. An inversion recovery turbo-FLASH sequence was applied and compared in terms of artifacts presence, efficiency for masking residual stool, and colonic wall conspicuity with a fat-saturated 3D FLASH sequence. Both sequences were acquired following administration of paramagnetic contrast agent. Contrast-to-noise ratio and relative contrast between colonic wall and lumen were calculated and compared for both sequences. Turbo 2D FLASH provided fewer artifacts, higher efficiency for masking the residual stool, and colonic wall conspicuity equivalent to 3D FLASH. An inversion time of 10 ms provided homogeneously low signal intensity of the colonic lumen. Contrast to noise between colonic wall and lumen was significantly higher in the 3D FLASH images, whereas differences in relative contrast were not statistically significant. An optimized inversion-recovery 2D turbo-FLASH sequence provides better fecal tagging results and should be added to the 3D FLASH sequence when designing dark-lumen MR colonography examination protocols. (orig.)

ALK and TGF-Beta Resistance in Breast Cancer

Science.gov (United States)

2017-10-01

Award Number: W81XWH‐15‐1‐0650 TITLE: ALK and TGF-Beta Resistance in Breast Cancer PRINCIPAL INVESTIGATOR: Xin-Hua Feng CONTRACTING...and TGF-Beta Resistance in Breast Cancer 5b. GRANT NUMBER W81XWH‐15‐1‐0650 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER Xin-Hua Feng...response is a hallmark in human cancer . However, the mechanisms underlying TGF- resistance in breast cancer have not been elucidated. Anaplastic

Ocular Changes in TgF344-AD Rat Model of Alzheimer's Disease

OpenAIRE

Tsai, Yuchun; Lu, Bin; Ljubimov, Alexander V.; Girman, Sergey; Ross-Cisneros, Fred N.; Sadun, Alfredo A.; Svendsen, Clive N.; Cohen, Robert M.; Wang, Shaomei

2014-01-01

In this study, we observed pathological changes in the choroid and in RPE cells in the TgF344-AD rat model; choroidal thinning was further observed in human AD retina. Along with Aβ deposition, the inflammatory response was manifested by microglial recruitment and complement activation.

Flash-Type Discrimination

Science.gov (United States)

Koshak, William J.

2010-01-01

This viewgraph presentation describes the significant progress made in the flash-type discrimination algorithm development. The contents include: 1) Highlights of Progress for GLM-R3 Flash-Type discrimination Algorithm Development; 2) Maximum Group Area (MGA) Data; 3) Retrieval Errors from Simulations; and 4) Preliminary Global-scale Retrieval.

The October 2014 United States Treasury bond flash crash and the contributory effect of mini flash crashes.

Directory of Open Access Journals (Sweden)

Zachary S Levine

Full Text Available We investigate the causal uncertainty surrounding the flash crash in the U.S. Treasury bond market on October 15, 2014, and the unresolved concern that no clear link has been identified between the start of the flash crash at 9:33 and the opening of the U.S. equity market at 9:30. We consider the contributory effect of mini flash crashes in equity markets, and find that the number of equity mini flash crashes in the three-minute window between market open and the Treasury Flash Crash was 2.6 times larger than the number experienced in any other three-minute window in the prior ten weekdays. We argue that (a this statistically significant finding suggests that mini flash crashes in equity markets both predicted and contributed to the October 2014 U.S. Treasury Bond Flash Crash, and (b mini-flash crashes are important phenomena with negative externalities that deserve much greater scholarly attention.

The October 2014 United States Treasury bond flash crash and the contributory effect of mini flash crashes.

Science.gov (United States)

Levine, Zachary S; Hale, Scott A; Floridi, Luciano

2017-01-01

We investigate the causal uncertainty surrounding the flash crash in the U.S. Treasury bond market on October 15, 2014, and the unresolved concern that no clear link has been identified between the start of the flash crash at 9:33 and the opening of the U.S. equity market at 9:30. We consider the contributory effect of mini flash crashes in equity markets, and find that the number of equity mini flash crashes in the three-minute window between market open and the Treasury Flash Crash was 2.6 times larger than the number experienced in any other three-minute window in the prior ten weekdays. We argue that (a) this statistically significant finding suggests that mini flash crashes in equity markets both predicted and contributed to the October 2014 U.S. Treasury Bond Flash Crash, and (b) mini-flash crashes are important phenomena with negative externalities that deserve much greater scholarly attention.

Flashing evaporation under different pressure levels

International Nuclear Information System (INIS)

Liao, Yixiang; Lucas, Dirk; Krepper, Eckhard; Rzehak, Roland

2013-01-01

Highlights: • CFD simulation based on two-fluid model for flashing boiling inside a vertical pipe. • Effect of pressure level on the maximum thermal energy available for evaporation. • Effect of presumed bubble size on the onset of flashing as well as evaporation rate. • Effect of pressure level on the critical bubble size that can start stable flashing. • Effect of pressure level on nucleation rate and mechanism. - Abstract: Flashing evaporation of water inside a vertical pipe under four pressure levels is investigated both experimentally and numerically. In the experiment depressurization is realized through a blow-off valve, and the evaporation rate is controlled by the opening rate and degree of the valve. In the CFD simulation phase change is assumed to be caused by thermal heat transfer between steam–water interface and the surrounding water. Consequently, the evaporation rate is determined by heat transfer coefficient, interfacial area density as well as liquid superheat degree. The simulated temporal course of cross-section averaged steam volume fraction is compared with the measured one. It is found that the increasing rate and maximum value of steam volume fraction is over-predicted under low-pressure conditions, which is mainly caused by the neglect of bubble growth in the mono-dispersed simulation. The agreement is notably improved by performing poly-dispersed simulations with the inhomogeneous MUSIG approach (IMUSIG). On the other hand an underestimation of the maximum steam volume fraction is observed in high-pressure cases, since the contribution of nucleation to the total steam generation rate becomes large as the system pressure increases. Reliable models for nucleation rate as well as bubble detachment size are indispensable for reliable predictions. An effect of the system pressure level on the nucleation mechanism is observed in the experiment

The benefit of high-resolution operational weather forecasts for flash flood warning

Directory of Open Access Journals (Sweden)

J. Younis

2008-07-01

Full Text Available In Mediterranean Europe, flash flooding is one of the most devastating hazards in terms of loss of human life and infrastructures. Over the last two decades, flash floods have caused damage costing a billion Euros in France alone. One of the problems of flash floods is that warning times are very short, leaving typically only a few hours for civil protection services to act. This study investigates if operationally available short-range numerical weather forecasts together with a rainfall-runoff model can be used for early indication of the occurrence of flash floods.

One of the challenges in flash flood forecasting is that the watersheds are typically small, and good observational networks of both rainfall and discharge are rare. Therefore, hydrological models are difficult to calibrate and the simulated river discharges cannot always be compared with ground measurements. The lack of observations in most flash flood prone basins, therefore, necessitates the development of a method where the excess of the simulated discharge above a critical threshold can provide the forecaster with an indication of potential flood hazard in the area, with lead times of the order of weather forecasts.

This study is focused on the Cévennes-Vivarais region in the Southeast of the Massif Central in France, a region known for devastating flash floods. This paper describes the main aspects of using numerical weather forecasting for flash flood forecasting, together with a threshold – exceedance. As a case study the severe flash flood event which took place on 8–9 September 2002 has been chosen.

Short-range weather forecasts, from the Lokalmodell of the German national weather service, are used as input for the LISFLOOD model, a hybrid between a conceptual and physically based rainfall-runoff model. Results of the study indicate that high resolution operational weather forecasting combined with a rainfall-runoff model could be useful to

The concomitant apoptosis and EMT underlie the fundamental functions of TGF-β.

Science.gov (United States)

Song, Jianguo; Shi, Weiwei

2018-01-01

TGF-β's multipotent cellular effects and their relations are critical for TGF-β's pathophysiological functions. However, these effects may appear to be paradoxical in understanding TGF-β's functions. Apoptosis and epithelial-mesenchymal transition (EMT) are two fundamental events that are deeply linked to various physiological and disease-related processes. These two major cellular fates are subtly regulated and can be potently stimulated by TGF-β, which profoundly contribute to the biological roles of TGF-β. Moreover, these two events are also indirectly and directly correlated with TGF-β-mediated growth inhibition and are relevant to the current understanding of the roles of TGF-β in tumorigenesis and cancer progression. Although TGF-β-induced apoptosis and EMT can be singly independent cellular events, they can also be mutually exclusive but interrelated concomitant events in various cases. Thus, the modulation of apoptosis and EMT is essential for the seemingly paradoxical functions of TGF-β. However, the concomitant effect of TGF-β on apoptosis and EMT, the balance and regulated alterations of them are still been ignored or underestimated. This review focuses on the TGF-β-induced concomitant apoptosis and EMT. We aim to provide an insight in understanding their significance, balance, and modulation in TGF-β-mediated biological functions. © The Author 2017. Published by Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

DIRCM FLASH Flight Tests

National Research Council Canada - National Science Library

Molocher, Bernhard; Kaltenecker, Anton; Thum-Jaeger, Andrea; Regensburger, Martin; Formery, Martin

2005-01-01

.... FLASH operation is as follows: After handover following an alarm from the missile warning system FLASH enters autonomous passive tracking mode for tracking a missiles and sending a laser beam onto the missile...

Wide Bandgap Semiconductor Detector Optimization for Flash X-Ray Measurements

Energy Technology Data Exchange (ETDEWEB)

Roecker, Caleb Daniel [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Schirato, Richard C. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

2017-11-17

Charge trapping, resulting in a decreased and spatially dependent electric field, has long been a concern for wide bandgap semiconductor detectors. While significant work has been performed to characterize this degradation at varying temperatures and radiation environments, this work concentrates upon examining the event-to-event response in a flash X-ray environment. The following work investigates if charge trapping is a problem for CZT detectors, with particular emphasis on flash X-ray radiation fields at cold temperatures. Results are compared to a non-flash radiation field, using an Am-241 alpha source and similar temperature transitions. Our ability to determine if a response change occurred was hampered by the repeatability of our flash X-ray systems; a small response change was observed with the Am-241 source. Due to contrast of these results, we are in the process of revisiting the Am-241 measurements in the presence of a high radiation environment. If the response change is more pronounced in the high radiation environment, a similar test will be performed in the flash X-ray environment.

TGF beta-1 dependent fast stimulation of ATM and p53 phosphorylation following exposure to ionizing radiation does not involve TGF beta-receptor I signalling

NARCIS (Netherlands)

Wiegman, Erwin M.; Blaese, Marcet A.; Loeffler, Heidi; Coppes, Rob P.; Rodemann, H. Peter

Background and purpose: It has been proposed that radiation induced stimulation of ATM and downstream components involves activation of TGF beta-1 and that this may be due to TGF beta-1-receptor I-Smad signalling. Therefore, the aim of this study was to clarify the distinct role of TGF

Liver fibrosis in bile duct-ligated rats correlates with increased hepatic IL-17 and TGF-β2 expression.

Science.gov (United States)

Zepeda-Morales, Adelaida Sara M; Del Toro-Arreola, Susana; García-Benavides, Leonel; Bastidas-Ramírez, Blanca E; Fafutis-Morris, Mary; Pereira-Suárez, Ana L; Bueno-Topete, Miriam R

2016-01-01

BACKGROUND AND RATIONALE FOR THE STUDY: IL-17, TGF-β1/2 are cytokines involved in the development of kidney, pulmonary and liver fibrosis. However, their expression kinetics in the pathogenesis of cholestatic liver fibrosis have not yet been fully explored. The aim of the study was to analyze the expression of IL-17, RORγt, NKp46, TGF-β1, and TGF-β2 in the liver of rats with bile duct ligation (BDL). Hepatic IL-17A gene expression analyzed by qRT-PCR showed a dramatic increase of 350 and 10 fold, at 8 and 30 days post BDL, respectively. TGFβ1 and TGFβ2 gene expression significantly increased throughout the whole fibrotic process. At the protein level in liver homogenates, IL-17, TGF-β1, and RORγt significantly increased at 8 and 30 days after BDL. Interestingly, a significant increase in the protein levels of TGF-β2 and decrease of NKp46 was observed only 30 days after BDL. Unexpectedly, TGF-β2 exhibited stronger signals than TGF-β1 at the gene expression and protein levels. Histological analysis showed bile duct proliferation and collagen deposition. Our results suggest that pro-fibrogenic cytokines IL-17, TGF-β1 and, strikingly, TGF-β2 might be important players of liver damage in the pathogenesis of early and advanced experimental cholestatic fibrosis. Th17 cells might represent an important source of IL-17, while NK cell depletion may account for the perpetuation of liver damage in the BDL model.

A novel method to alleviate flash-line defects in coining process

KAUST Repository

Xu, Jiangping

2013-04-01

We employ a finite element framework based on a dynamic explicit algorithm to predict the flash-line defects in the coining process. The distribution of the flash-line is obtained by building a radial friction work model at the element level. The elasto-plastic behavior of porous materials undergoing large deformations is considered where the constitutive level updates are the result of a local variational minimization problem. We study the material flow at different strokes of the die across the entire coining process and observe that the change in the flow direction of the material in the rim region may contribute to the flash lines. Our proposed framework shows that a part of the rim region in which the flash-line defects appear is consistent with the reported experimental results. We also propose a novel method of redesigning the rim geometry of the workpiece to alleviate the flash-line defects which also shows good agreement with experiments. © 2012 Elsevier Inc. All rights reserved.

Role of TGF-β on cardiac structural and electrical remodeling

Directory of Open Access Journals (Sweden)

Roberto Ramos-Mondragón

2008-12-01

Full Text Available Roberto Ramos-Mondragón, Carlos A Galindo, Guillermo AvilaDepartamento de Bioquímica, Cinvestav-IPN, MéxicoAbstract: The type β transforming growth factors (TGF-βs are involved in a number of human diseases, including heart failure and myocardial arrhythmias. In fact, during the last 20 years numerous studies have demonstrated that TGF-β affects the architecture of the heart under both normal and pathological conditions. Moreover, TGF-β signaling is currently under investigation, with the aim of discovering potential therapeutic roles in human disease. In contrast, only few studies have investigated whether TGF-β affects electrophysiological properties of the heart. This fact is surprising since electrical remodeling represents an important substrate for cardiac disease. This review discusses the potential role of TGF-β on cardiac excitation-contraction (EC coupling, action potentials, and ion channels. We also discuss the effects of TGF-β on cardiac development and disease from structural and electrophysiological points of view.Keywords: transforming growth factor, ion channel, cardiac electrophysiology

TBX3, a downstream target of TGF-β1, inhibits mesangial cell apoptosis

Energy Technology Data Exchange (ETDEWEB)

Wensing, Lislaine A. [Hospital Israelita Albert Einstein, Av. Albert Einstein, 627, Morumbi, 2SS/Bloco A., São Paulo, São Paulo CEP 05651-901 (Brazil); Departamento de Fisiologia e Biofísica, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo (Brazil); Campos, Alexandre H., E-mail: alexandre.campos@einstein.br [Hospital Israelita Albert Einstein, Av. Albert Einstein, 627, Morumbi, 2SS/Bloco A., São Paulo, São Paulo CEP 05651-901 (Brazil)

2014-11-01

Chronic kidney disease (CKD) is an increasingly common condition characterized by progressive loss of functional nephrons leading to renal failure. TGF-β1-induced mesangial cell (MC) phenotype alterations have been linked to the genesis of CKD. Here we show that TGF-β1 regulates TBX3 gene expression in MC. This gene encodes for two main isoforms, TBX3.1 and TBX3+2α. TBX3.1 has been implicated in cell immortalization, proliferation and apoptosis by inhibiting p14{sup ARF}-Mdm2-p53 pathway, while TBX3+2α role has not been defined. We demonstrated that TBX3 overexpression abrogated MC apoptosis induced by serum deprivation. Moreover, we observed an enhancement in TBX3 protein expression both in glomerular and tubular regions in the model of 5/6 nephrectomy, temporally related to increased expression of TGF-β1, type IV collagen and fibronectin. Our results indicate that TBX3 acts as an anti-apoptotic factor in MC in vitro and may be involved in the mechanism by which TGF-β1 induces glomerulosclerosis and tubular fibrosis during the progression of nephropathies. - Highlights: • TBX3 isoforms are upregulated by TGF-b1 in mesangial cells. • TBX3 isoforms have different subcellular distribution profile in mesangial cells. • TBX3 isoforms exhibit antiapoptotic action in mesangial cells. • TBX3 protein is overexpressed in a model of nephropathy (5/6 nephrectomy)

Flashing inception in flowing liquids

International Nuclear Information System (INIS)

Jones, O.C. Jr.

1979-01-01

The inception of net vaporization in flashing flows is examined. It is suggested that the flashing inception can be expressed as two additive effects. One is due to the static decompression which is a function of the spinodal limit and also of the expansion rate. The other effect which is a function of Reynolds number and flashing index, is due to the turbulent fluctuations of the flowing liquid. It is shown that by taking a three standard deviation band on the turbulent velocity fluctuations, an adequate representation of the inverse mass flux effect on flashing inception for existing data is obtained

Statistical Evolution of the Lightning Flash

Science.gov (United States)

Zoghzoghy, F. G.; Cohen, M.; Said, R.; Inan, U. S.

2012-12-01

Natural lightning is one of the most fascinating and powerful electrical processes on Earth. To date, the physics behind this natural phenomenon are not fully understood, due primarily to the difficulty of obtaining measurements inside thunderstorms and to the wide range of timescales involved (from nanoseconds to seconds). Our aim is to use accurate lightning geo-location data from the National Lightning Detection Network (NLDN) to study statistical patterns in lightning, taking advantage of the fact that millions of lightning flashes occur around the globe every day. We present two sets of results, one involving the patterns of flashes in a storm, and a second involving the patterns of strokes in a flash. These patterns can provide a surrogate measure of the timescales and the spatial extents of the underlying physical processes. First, we study the timescales of charge buildup inside thunderstorms. We find that, following a lightning flash, the probability of another neighboring flash decreases and takes tens of seconds to recover. We find that this suppression effect is a function of flash type, stroke peak current, cloud-to-ground (CG) stroke multiplicity, and other lightning and geographical parameters. We find that the probabilities of subsequent flashes are more suppressed following oceanic lightning, or following flashes with higher peak currents and/or higher multiplicities (for CG flashes). Second, we use NLDN data to study the evolution of the strokes within a CG flash. A CG flash typically includes multiple return strokes, which can occur in the same channel or in multiple channels within a few kilometers. We cluster NLDN stroke data into flashes and produce the probability density function of subsequent strokes as a function of distance and time-delays relative to the previous stroke. Using this technique, we investigate processes which occur during the CG lightning flash with nanosecond to millisecond timescales. For instance, our results suggest

Inhibition of the αvβ6 integrin leads to limited alteration of TGF-α-induced pulmonary fibrosis

Science.gov (United States)

Madala, Satish K.; Korfhagen, Thomas R.; Schmidt, Stephanie; Davidson, Cynthia; Edukulla, Ramakrishna; Ikegami, Machiko; Violette, Shelia M.; Weinreb, Paul H.; Sheppard, Dean

2014-01-01

the β6 integrin attenuated histological and physiological changes in the lungs of TGF-α transgenic mice although a significant degree of fibrosis still developed. In summary, inhibition of the β6 integrin led to a modest, albeit significant, effect on pleural thickening and lung function decline observed with TGF-α-induced pulmonary fibrosis. These data support activation of the αvβ6/TGF-β pathway as a secondary effect contributing to TGF-α-induced pleural fibrosis and suggest a complex contribution of multiple mediators to the maintenance of progressive fibrosis in the lung. PMID:24508732

TGF-beta1 expression in EL4 lymphoma cells overexpressing growth hormone.

Science.gov (United States)

Farmer, John T; Weigent, Douglas A

2006-03-01

Our previous studies show that growth hormone overexpression (GHo) upregulates the expression of the IGF-1R and IGF-2R resulting in the protection of the EL4 lymphoma cell line from apoptosis. In this study, we report that GHo also increases TGF-beta1 protein expression measured by luciferase promoter assay, Western analysis, and ELISA. Further, the data show that antibody to TGF-betaR2 decreases TGF-beta1 promoter activity to the level of vector alone control cells. GHo cells treated with (125)I-rh-latent TGF-beta1 showed increased activation of latent TGF-beta1 as measured by an increase in the active 24kDa, TGF-beta1 compared to vector alone control cells. The ability of endogenous GH to increase TGF-beta1 expression is blocked in EL4 cells by antisense but not sense oligodeoxynucleotides or in cells cultured with antibody to growth hormone (GH). The data suggest that endogenous GH may protect from apoptosis through the IGF-1R receptor while limiting cellular growth through increased expression and activation of TGF-beta1.

TGF-beta and 'adaptive' Foxp3(+) regulatory T cells.

Science.gov (United States)

Chen, Wanjun; Konkel, Joanne E

2010-02-01

In naïve T cells transforming growth factor-beta (TGF-beta) induces Foxp3, a transcription factor essential for programming and developing T regulatory cells (Treg cells). This finding reveals a physiological factor which can turn on the Foxp3 gene and establishes an experimental approach to induce antigen-specific Treg cells as a potential therapy for human diseases. While this role for TGF-beta is well confirmed, several critical questions remain largely unanswered and await further investigation. In this regard, it is imperative to understand the molecular pathways by which TGF-beta signaling initiates and regulates Foxp3 expression. It is also important to elucidate which factors and/or cytokines influence the TGF-beta-mediated conversion of naïve T cells and how to create an immunologically regulatory milieu to facilitate Treg cell generation in vivo. In this short article, we will highlight the key findings and recent progress in the field, discuss the molecular mechanisms underlying the TGF-beta-mediated induction of Foxp3, and attempt to outline the challenges ahead.

TGF-β1 exerts opposing effects on grass carp leukocytes: implication in teleost immunity, receptor signaling and potential self-regulatory mechanisms.

Directory of Open Access Journals (Sweden)

Mu Yang

Full Text Available In fish immunity, the regulatory role of transforming growth factor-β1 (TGF-β1 has not been fully characterized. Here we examined the immunoregulatory effects of TGF-β1 in grass carp peripheral blood leukocytes (PBL and head kidney leukocytes (HKL. It is interesting that TGF-β1 consistently stimulated the cell viability and the mRNA levels of pro-inflammatory cytokines (Tnfα and Ifnγ and T/B cell markers [Cd4-like (Cd4l, Cd8α, Cd8β and Igμ] in PBL, which contrasted with its inhibitory tone in HKL. Further studies showed that grass carp TGF-β1 type I receptor, activin receptor-like kinase 5 (ALK5, was indispensable for the immunoregulatory effects of TGF-β1 in PBL and HKL. Notably, TGF-β1 persistently attenuated ALK5 expression, whereas immunoneutralization of endogenous grass carp TGF-β1 could increase ALK5 mRNA and protein levels. It is consistent with the observation that TGF-β1 decreased the number of ALK5(+ leukocytes in PBL and HKL, revealing a negative regulation of TGF-β1 signaling at the receptor level. Moreover, transient treatment with TGF-β1 for 24 h was sufficient to induce similar cellular responses compared with the continuous treatment. This indicated a possible mechanism by which TGF-β1 triggered the down-regulation of ALK5 mRNA and protein, leading to the desensitization of grass carp leukocytes toward TGF-β1. Accordingly, our data revealed a dual role of TGF-β1 in teleost immunity in which it can serve as a positive or negative control device and provided additional mechanistic insights as to how TGF-β1 controls its signaling in vertebrate leukocytes.

Smad7 induces tumorigenicity by blocking TGF-beta-induced growth inhibition and apoptosis.

Science.gov (United States)

Halder, Sunil K; Beauchamp, R Daniel; Datta, Pran K

2005-07-01

Smad proteins play a key role in the intracellular signaling of the transforming growth factor beta (TGF-beta) superfamily of extracellular polypeptides that initiate signaling to regulate a wide variety of biological processes. The inhibitory Smad, Smad7, has been shown to function as intracellular antagonists of TGF-beta family signaling and is upregulated in several cancers. To determine the effect of Smad7-mediated blockade of TGF-beta signaling, we have stably expressed Smad7 in a TGF-beta-sensitive, well-differentiated, and non-tumorigenic cell line, FET, that was derived from human colon adenocarcinoma. Smad7 inhibits TGF-beta-induced transcriptional responses by blocking complex formation between Smad 2/3 and Smad4. While Smad7 has no effect on TGF-beta-induced activation of p38 MAPK and ERK, it blocks the phosphorylation of Akt by TGF-beta and enhances TGF-beta-induced phosphorylation of c-Jun. FET cells expressing Smad7 show anchorage-independent growth and enhance tumorigenicity in athymic nude mice. Smad7 blocks TGF-beta-induced growth inhibition by preventing TGF-beta-induced G1 arrest. Smad7 inhibits TGF-beta-mediated downregulation of c-Myc, CDK4, and Cyclin D1, and suppresses the expression of p21(Cip1). As a result, Smad7 inhibits TGF-beta-mediated downregulation of Rb phosphorylation. Furthermore, Smad7 inhibits the apoptosis of these cells. Together, Smad7 may increase the tumorigenicity of FET cells by blocking TGF-beta-induced growth inhibition and by inhibiting apoptosis. Thus, this study provides a mechanism by which a portion of human colorectal tumors may become refractory to tumor-suppressive actions of TGF-beta that might result in increased tumorigenicity.

Substrate stiffness promotes latent TGF-β1 activation in hepatocellular carcinoma

International Nuclear Information System (INIS)

Pang, Mingshu; Teng, Yao; Huang, Jianyong; Yuan, Yuan; Lin, Feng; Xiong, Chunyang

2017-01-01

Hepatocellular carcinoma (HCC) was usually coupled with increased stiffness of the extracellular matrix (ECM) and elevated level of transforming growth factor-β1 (TGF-β1). However, the mechanism by which substrate rigidity modulated TGF-β1 signaling transduction remained unknown. This paper investigated the molecular mechanism of how matrix stiffness regulating TGF-β1 signaling in HCC cells. By means of stiffness tunable collagen I-coated polyacrylamide (PA) gels, we found that the expressions of β1 integrin, p-FAK Y397 and p-Smad2 upregulated on stiffer gels as well as the content of TGF-β1 in culture media of HCC cells, which were inhibited by RGD blocking peptides, Y-27632 (ROCK inhibitor) or Blebbistatin (myosin II inhibitor). Cellular traction force was also significantly higher when plated on stiffer substrates but dramatically decreased after treatment with Y-27632 or Blebbistatin. Furthermore, the upregulation of p-Smad2 in the HCC cells on stiffer PA gels induced by exogenetic latent TGF-β1 was downregulated in the presence of RGD peptides. The nuclear translocation of Smad2 induced by latent TGF-β1 was inhibited by Y-27632 or Blebbistatin. Our results suggested that the extracellular matrix stiffness regulated latent TGF-β1 activation by cytoskeletal tension in HCC cells, showing that matrix stiffness was a key regulator involving the TGF-β1 activity in HCC cells. The current study presented a mechanism of how hepatocirrhosis developed into liver cancer. - Highlights: • TGF-β1 signaling pathway regulated by ECM stiffness was studied in hepatocellular carcinoma. • Matrix stiffness promoted latent TGF-β1 activation via β1 integrin-FAK-Rho GTPase pathway. • A mechanism of how hepatocirrhosis developed into liver cancer was presented.

Foundation Flash CS4 for Designers

CERN Document Server

Green, Tom

2008-01-01

In this book, you'll learn:* How to create effective animations using the new Motion Editor and animation tools * How to use the new 3D features to animate objects in 3D space * Best-practice tips and techniques from some of the top Flash practitioners on the planet * How to create captioned video and full-screen video, and deploy HD video using Flash * Techniques for using the Flash UI components as well as XML documents to create stunning,interactive presentations If you're a Flash designer looking for a solid overview of Flash CS4, this book is for you. Through the use of solid and practica

Transforming growth factor (TGF)-β signalling is increased in rheumatoid synovium but TGF-β blockade does not modify experimental arthritis.

Science.gov (United States)

Gonzalo-Gil, E; Criado, G; Santiago, B; Dotor, J; Pablos, J L; Galindo, M

2013-11-01

The aim of this study was to analyse the distribution of regulatory and inhibitory mothers against decapentaplegic homologue (Smad) proteins as markers of active transforming growth factor (TGF)-β signalling in rheumatoid arthritis (RA) synovial tissue and to investigate the effect of TGF-β blockade in the development and progression of collagen-induced arthritis. The expression of Smad proteins in synovial tissues from RA, osteoarthritic and healthy controls was analysed by immunohistochemistry. Arthritis was induced in DBA/1 mice by immunization with chicken type-II collagen (CII). TGF-β was blocked in vivo with the specific peptide p17 starting at the time of immunization or on the day of arthritis onset. T cell population frequencies and specific responses to CII were analysed. The expression of cytokines and transcription factors was quantified in spleen and joint samples. Statistical differences between groups were compared using the Mann-Whitney U-test or one-way analysis of variance (anova) using the Kruskal-Wallis test. p-Smad-2/3 and inhibitory Smad-7 expression were detected in RA and control tissues. In RA, most lymphoid infiltrating cells showed nuclear p-Smad-2/3 without Smad-7 expression. Treatment with TGF-β antagonist did not affect clinical severity, joint inflammation and cartilage damage in collagen-induced arthritis. Frequency of T cell subsets, mRNA levels of cytokines and transcription factors, specific proliferation to CII, serum interleukin (IL)-6 and anti-CII antibodies were comparable in p17 and phosphate-buffered saline (PBS)-treated groups. The pattern of Smad proteins expression demonstrates active TGF-β signalling in RA synovium. However, specific TGF-β blockade does not have a significant effect in the mice model of collagen-induced arthritis. © 2013 British Society for Immunology.

Detection of Malicious Flash Banner Advertisements

Directory of Open Access Journals (Sweden)

Kirill Alekseevich Samosadnyy

2014-09-01

Full Text Available The paper addresses the problem of detecting malicious flash advertisements. As a result, detection method based on dynamic analysis that modify flash application and execute it in Adobe Flash player is proposed and evaluated on synthetic and real world examples.

Role of TGF-β in a Mouse Model of High Turnover Renal Osteodystrophy†

Science.gov (United States)

Liu, Shiguang; Song, Wenping; Boulanger, Joseph H; Tang, Wen; Sabbagh, Yves; Kelley, Brian; Gotschall, Russell; Ryan, Susan; Phillips, Lucy; Malley, Katie; Cao, Xiaohong; Xia, Tai-He; Zhen, Gehua; Cao, Xu; Ling, Hong; Dechow, Paul C; Bellido, Teresita M; Ledbetter, Steven R; Schiavi, Susan C

2014-01-01

Altered bone turnover is a key pathologic feature of chronic kidney disease-mineral and bone disorder (CKD-MBD). Expression of TGF-β1, a known regulator of bone turnover, is increased in bone biopsies from individuals with CKD. Similarly, TGF-β1 mRNA and downstream signaling is increased in bones from jck mice, a model of high-turnover renal osteodystropy. A neutralizing anti-TGF-β antibody (1D11) was used to explore TGF-βs role in renal osteodystrophy. 1D11 administration to jck significantly attenuated elevated serum osteocalcin and type I collagen C-telopeptides. Histomorphometric analysis indicated that 1D11 administration increased bone volume and suppressed the elevated bone turnover in a dose-dependent manner. These effects were associated with reductions in osteoblast and osteoclast surface areas. μCT confirmed the observed increase in trabecular bone volume and demonstrated improvements in trabecular architecture and increased cortical thickness. 1D11 administration was associated with significant reductions in expression of osteoblast marker genes (Runx2, alkaline phosphatase, osteocalcin) and the osteoclast marker gene, Trap5. Importantly, in this model, 1D11 did not improve kidney function or reduce serum PTH levels indicating that 1D11 effects on bone are independent of changes in renal or parathyroid function. 1D11 also significantly attenuated high turnover bone disease in the adenine-induced uremic rat model. Antibody administration was associated with a reduction in pSMAD2/SMAD2 in bone but not bone marrow as assessed by quantitative immunoblot analysis. Immunostaining revealed pSMAD staining in osteoblasts and osteocytes but not osteoclasts, suggesting 1D11 effects on osteoclasts may be indirect. Immunoblot and whole genome mRNA expression analysis confirmed our previous observation that repression of Wnt/β catenin expression in bone is correlated with increased osteoclast activity in jck mice and bone biopsies from CKD patients. Furthermore

COBRAT Project: Long duration balloons for the study of high energy phenomena and consequences for stratospheric chemistry

DEFF Research Database (Denmark)

Renard, Jean-Baptiste; Berthet, Gwenaël; Catoire, Valéry

2010-01-01

The study of the Transient Luminous Events (TLE) and of the Terrestrial Gamma-ray Flashes (TGF) will be performed soon by the satellite instruments TARANIS (CNES) and ASIM (ESA, onboard the International Space Station). In complement to these measurements, observations are proposed to be conducte...

On multiphase negative flash for ideal solutions

DEFF Research Database (Denmark)

Yan, Wei; Stenby, Erling Halfdan

2012-01-01

simpler than the corresponding normal flash algorithm. Unlike normal flash, multiphase negative flash for ideal solutions can diverge if the feasible domain for phase amounts is not closed. This can be judged readily during the iteration process. The algorithm can also be extended to the partial negative......There is a recent interest to solve multiphase negative flash problems where the phase amounts can be negative for normal positive feed composition. Solving such a negative flash problem using successive substitution needs an inner loop for phase distribution calculation at constant fugacity...... coefficients. It is shown that this inner loop, named here as multiphase negative flash for ideal solutions, can be solved either by Michelsen's algorithm for multiphase normal flash, or by its variation which uses F−1 phase amounts as independent variables. In either case, the resulting algorithm is actually...

Measuring hot flash phenomenonology using ambulatory prospective digital diaries

Science.gov (United States)

Fisher, William I.; Thurston, Rebecca C.

2016-01-01

Objective This study provides the description, protocol, and results from a novel prospective ambulatory digital hot flash phenomenon diary. Methods This study included 152 midlife women with daily hot flashes who completed an ambulatory electronic hot flash diary continuously for the waking hours of 3 consecutive days. In this diary, women recorded their hot flashes and accompanying characteristics and associations as the hot flashes occurred. Results Self-reported hot flash severity on the digital diaries indicated that the majority of hot flashes were rated as mild (41.3%) or moderate (43.7%). Severe (13.1%) and very severe (1.8%) hot flashes were less common. Hot flash bother ratings were rated as mild (43%), or moderate (33.5%), with fewer hot flashes reported bothersome (17.5%) or very bothersome (6%). The majority of hot flashes were reported as occurring on the on the face (78.9%), neck (74.7%), and chest (61.3%). Prickly skin was reported concurrently with 32% of hot flashes, 7% with anxiety and 5% with nausea. A novel finding, 38% of hot flashes were accompanied by a premonitory aura. Conclusion A prospective electronic digital hot flash diary allows for a more precise quantitation of hot flashes while overcoming many of the limitations of commonly employed retrospective questionnaires and paper diaries. Unique insights into the phenomenology, loci and associated characteristics of hot flashes were obtained using this device. The digital hot flash phenomenology diary is recommended for future ambulatory studies of hot flashes as a prospective measure of the hot flash experience. PMID:27404030

TGF-β prevents phosphate-induced osteogenesis through inhibition of BMP and Wnt/β-catenin pathways.

Directory of Open Access Journals (Sweden)

Fátima Guerrero

Full Text Available BACKGROUND: Transforming growth factor-β (TGF-β is a key cytokine during differentiation of mesenchymal stem cells (MSC into vascular smooth muscle cells (VSMC. High phosphate induces a phenotypic transformation of vascular smooth muscle cells (VSMC into osteogenic-like cells. This study was aimed to evaluate signaling pathways involved during VSMC differentiation of MSC in presence or not of high phosphate. RESULTS: Our results showed that TGF-β induced nuclear translocation of Smad3 as well as the expression of vascular smooth muscle markers, such as smooth muscle alpha actin, SM22α, myocardin, and smooth muscle-myosin heavy chain. The addition of high phosphate to MSC promoted nuclear translocation of Smad1/5/8 and the activation of canonical Wnt/β-catenin in addition to an increase in BMP-2 expression, calcium deposition and alkaline phosphatase activity. The administration of TGF-β to MSC treated with high phosphate abolished all these effects by inhibiting canonical Wnt, BMP and TGF-β pathways. A similar outcome was observed in high phosphate-treated cells after the inhibition of canonical Wnt signaling with Dkk-1. Conversely, addition of both Wnt/β-catenin activators CHIR98014 and lithium chloride enhanced the effect of high phosphate on BMP-2, calcium deposition and alkaline phosphatase activity. CONCLUSIONS: Full VSMC differentiation induced by TGF-β may not be achieved when extracellular phosphate levels are high. Moreover, TGF-β prevents high phosphate-induced osteogenesis by decreasing the nuclear translocation of Smad 1/5/8 and avoiding the activation of Wnt/β-catenin pathway.

The role of TGF-β in polycystic ovary syndrome.

Science.gov (United States)

Raja-Khan, Nazia; Urbanek, Margrit; Rodgers, Raymond J; Legro, Richard S

2014-01-01

Polycystic ovary syndrome (PCOS) is a common endocrine disorder characterized by chronic oligoanovulation and hyperandrogenism and associated with insulin resistance, type 2 diabetes, and cardiovascular risk. In recent years, genetic studies have linked PCOS to a dinucleotide marker D19S884 in the fibrillin 3 gene. Fibrillins make up the major component of microfibrils in the extracellular matrix (ECM) and interact with molecules in the ECM to regulate transforming growth factor β (TGF-β) signaling. Therefore, variations in fibrillin 3 and subsequent dysregulation of TGF-β may contribute to the pathogenesis of PCOS. Here, we review the evidence from genetic studies supporting the role of TGF-β in PCOS and describe how TGF-β dysregulation may contribute to (1) the fetal origins of PCOS, (2) reproductive abnormalities in PCOS, and (3) cardiovascular and metabolic abnormalities in PCOS.

Flash Floods Simulation using a Physical-Based Hydrological Model at Different Hydroclimatic Regions

Science.gov (United States)

Saber, Mohamed; Kamil Yilmaz, Koray

2016-04-01

Currently, flash floods are seriously increasing and affecting many regions over the world. Therefore, this study will focus on two case studies; Wadi Abu Subeira, Egypt as arid environment, and Karpuz basin, Turkey as Mediterranean environment. The main objective of this work is to simulate flash floods at both catchments considering the hydrometeorological differences between them which in turn effect their flash flood behaviors. An integrated methodology incorporating Hydrological River Basin Environmental Assessment Model (Hydro-BEAM) and remote sensing observations was devised. Global Satellite Mapping of Precipitation (GSMAP) were compared with the rain gauge network at the target basins to estimate the bias in an effort to further use it effectively in simulation of flash floods. Based on the preliminary results of flash floods simulation on both basins, we found that runoff behaviors of flash floods are different due to the impacts of climatology, hydrological and topographical conditions. Also, the simulated surface runoff hydrographs are reasonably coincide with the simulated ones. Consequently, some mitigation strategies relying on this study could be introduced to help in reducing the flash floods disasters at different climate regions. This comparison of different climatic basins would be a reasonable implication for the potential impact of climate change on the flash floods frequencies and occurrences.

Emergence, development and diversification of the TGF-beta signalling pathway within the animal kingdom.

Science.gov (United States)

Huminiecki, Lukasz; Goldovsky, Leon; Freilich, Shiri; Moustakas, Aristidis; Ouzounis, Christos; Heldin, Carl-Henrik

2009-02-03

The question of how genomic processes, such as gene duplication, give rise to co-ordinated organismal properties, such as emergence of new body plans, organs and lifestyles, is of importance in developmental and evolutionary biology. Herein, we focus on the diversification of the transforming growth factor-beta (TGF-beta) pathway -- one of the fundamental and versatile metazoan signal transduction engines. After an investigation of 33 genomes, we show that the emergence of the TGF-beta pathway coincided with appearance of the first known animal species. The primordial pathway repertoire consisted of four Smads and four receptors, similar to those observed in the extant genome of the early diverging tablet animal (Trichoplax adhaerens). We subsequently retrace duplications in ancestral genomes on the lineage leading to humans, as well as lineage-specific duplications, such as those which gave rise to novel Smads and receptors in teleost fishes. We conclude that the diversification of the TGF-beta pathway can be parsimoniously explained according to the 2R model, with additional rounds of duplications in teleost fishes. Finally, we investigate duplications followed by accelerated evolution which gave rise to an atypical TGF-beta pathway in free-living bacterial feeding nematodes of the genus Rhabditis. Our results challenge the view of well-conserved developmental pathways. The TGF-beta signal transduction engine has expanded through gene duplication, continually adopting new functions, as animals grew in anatomical complexity, colonized new environments, and developed an active immune system.

Acquired TGF beta 1 sensitivity and TGF beta 1 expression in cell lines established from a single small cell lung cancer patient during clinical progression

DEFF Research Database (Denmark)

Nørgaard, P; Damstrup, L; Rygaard, K

1996-01-01

Three small cell lung cancer cell lines established from a single patient during longitudinal follow-up were examined for in vitro expression of TGF beta and TGF beta receptors, i.e. the components of an autocrine loop. GLC 14 was established prior to treatment, GLC 16 on relapse after chemotherapy...... was found in GLC 16 and GLC 19. These cell lines were also growth inhibited by exogenously administrated TGF beta 1. TGF beta 1 mRNA and protein in its latent form was only expressed in the radiotherapy-resistant cell line, GLC 19. The results indicate that disease progression in this patient was paralleled...... II receptor gene, as examined by Southern blotting. Also, the type I receptor could not be detected by ligand binding assay in this cell line, despite expression of mRNA for this receptor. This agrees with previous findings that type I receptor cannot bind TGF beta 1 without co-expression of the type...

An improved lightning flash rate parameterization developed from Colorado DC3 thunderstorm data for use in cloud-resolving chemical transport models

Science.gov (United States)

Basarab, B. M.; Rutledge, S. A.; Fuchs, B. R.

2015-09-01

Accurate prediction of total lightning flash rate in thunderstorms is important to improve estimates of nitrogen oxides (NOx) produced by lightning (LNOx) from the storm scale to the global scale. In this study, flash rate parameterization schemes from the literature are evaluated against observed total flash rates for a sample of 11 Colorado thunderstorms, including nine storms from the Deep Convective Clouds and Chemistry (DC3) experiment in May-June 2012. Observed flash rates were determined using an automated algorithm that clusters very high frequency radiation sources emitted by electrical breakdown in clouds and detected by the northern Colorado lightning mapping array. Existing schemes were found to inadequately predict flash rates and were updated based on observed relationships between flash rate and simple storm parameters, yielding significant improvement. The most successful updated scheme predicts flash rate based on the radar-derived mixed-phase 35 dBZ echo volume. Parameterizations based on metrics for updraft intensity were also updated but were found to be less reliable predictors of flash rate for this sample of storms. The 35 dBZ volume scheme was tested on a data set containing radar reflectivity volume information for thousands of isolated convective cells in different regions of the U.S. This scheme predicted flash rates to within 5.8% of observed flash rates on average. These results encourage the application of this scheme to larger radar data sets and its possible implementation into cloud-resolving models.

Proteomic profiling of bone marrow mesenchymal stem cells upon TGF-beta stimulation

Energy Technology Data Exchange (ETDEWEB)

Wang, Daojing; Park, Jennifer S.; Chu, Julia S.F.; Ari, Krakowski; Luo, Kunxin; Chen, David J.; Li, Song

2004-08-08

Bone marrow mesenchymal stem cells (MSCs) can differentiate into different types of cells, and have tremendous potential for cell therapy and tissue engineering. Transforming growth factor {beta}1 (TGF-{beta}) plays an important role in cell differentiation and vascular remodeling. We showed that TGF-{beta} induced cell morphology change and an increase in actin fibers in MSCs. To determine the global effects of TGF-{beta} on MSCs, we employed a proteomic strategy to analyze the effect of TGF-{beta} on the human MSC proteome. By using two-dimensional gel electrophoresis and electrospray ionization coupled to Quadrupole/time-of-flight tandem mass spectrometers, we have generated a proteome reference map of MSCs, and identified {approx}30 proteins with an increase or decrease in expression or phosphorylation in response to TGF-{beta}. The proteins regulated by TGF-{beta} included cytoskeletal proteins, matrix synthesis proteins, membrane proteins, metabolic enzymes, etc. TGF-{beta} increased the expression of smooth muscle (SM) {alpha}-actin and decreased the expression of gelsolin. Over-expression of gelsolin inhibited TGF-{beta}-induced assembly of SM {alpha}-actin; on the other hand, knocking down gelsolin expression enhanced the assembly of {alpha}-actin and actin filaments without significantly affecting {alpha}-actin expression. These results suggest that TGF-{beta} coordinates the increase of {alpha}-actin and the decrease of gelsolin to promote MSC differentiation. This study demonstrates that proteomic tools are valuable in studying stem cell differentiation and elucidating the underlying molecular mechanisms.

Cloud-to-ground lightning flash characteristics from June 1984 through May 1985

Science.gov (United States)

Orville, Richard E.; Weisman, Robert A.; Pyle, Richard B.; Henderson, Ronald W.; Orville, Richard E., Jr.

1987-01-01

A magnetic direction-finding network for the detection of lightning cloud-to-ground strikes has been installed along the east coast of the United States. Time, location, flash polarity, stroke count, and peak signal amplitude are recorded in real time. The data were recorded from Maine to North Carolina and as far west as Ohio; analyses were restricted to flashes within 300 km of a direction finder. Measurements of peak signal strength have been obtained from 720,284 first return strokes lowering negative charge. The resulting distribution indicates that few negative strokes have peak currents exceeding 100 kA. Measurements have also been obtained of peak signal strength from 17,694 first return strokes lowering positive charge. These strokes have a median peak current of 45 kA, with some peak currents reaching 300-400 kA. The median peak signal strength and the peak current, double from summer to winter for both negative and positive first return strokes. The polarity of ground flashes is observed to be less than 5 percent positive throughout the summer and early fall, then increases to over 50 percent during the winter, and returns to less than 10 percent in early spring. The percent of positive flashes with one stroke is observed to be approximately 90 percent throughout the year. The percent of negative flashes with one stroke is observed to increase from 40 percent in the summer to approximately 80 percent in January, returning to less than 50 percent in the spring.

Characterization of pancreatic lesions from MT-tgf alpha, Ela-myc and MT-tgf alpha/Ela-myc single and double transgenic mice.

Science.gov (United States)

Liao, Dezhong Joshua; Wang, Yong; Wu, Jiusheng; Adsay, Nazmi Volkan; Grignon, David; Khanani, Fayyaz; Sarkar, Fazlul H

2006-07-05

In order to identify good animal models for investigating therapeutic and preventive strategies for pancreatic cancer, we analyzed pancreatic lesions from several transgenic models and made a series of novel findings. Female MT-tgf alpha mice of the MT100 line developed pancreatic proliferation, acinar-ductal metaplasia, multilocular cystic neoplasms, ductal adenocarcinomas and prominent fibrosis, while the lesions in males were less severe. MT-tgf alpha-ES transgenic lines of both sexes developed slowly progressing lesions that were similar to what was seen in MT100 males. In both MT100 and MT-tgf alpha-ES lines, TGF alpha transgene was expressed mainly in proliferating ductal cells. Ela-myc transgenic mice with a mixed C57BL/6, SJL and FVB genetic background developed pancreatic tumors at 2-7 months of age, and half of the tumors were ductal adenocarcinomas, similar to what was reported originally by Sandgren et al 1. However, in 20% of the mice, the tumors metastasized to the liver. MT100/Ela-myc and MT-tgf alpha-ES/Ela-myc double transgenic mice developed not only acinar carcinomas and mixed carcinomas as previously reported but also various ductal-originated lesions, including multilocular cystic neoplasms and ductal adenocarcinomas. The double transgenic tumors were more malignant and metastasized to the liver at a higher frequency (33%) compared with the Ela-myc tumors. Sequencing of the coding region of p16ink4, k-ras and Rb cDNA in small numbers of pancreatic tumors did not identify mutations. The short latency for tumor development, the variety of tumor morphology and the liver metastases seen in Ela-myc and MT-tgf alpha/Ela-myc mice make these animals good models for investigating new therapeutic and preventive strategies for pancreatic cancer.

Flash Extraction and Physicochemical Characterization of Oil from Elaeagnus mollis Diels Seeds.

Science.gov (United States)

Kan, Lina; Wang, Lin; Ding, Qingzhen; Wu, Yanwen; Ouyang, Jie

2017-04-03

A flash extraction method was used to isolate Elaeagnus mollis oil (EMO). The optimal extraction parameters, sample/solvent ratio and extraction temperature, were determined to be 1:10 (g/mL) and 40°C, respectively. Especially, the extraction yield reached 49.30% when the extraction time was as short as 2 min. No obvious difference was observed in fatty acid composition, iodine value, saponification number, total phenolic content and tocopherol content between flash-extracted EMO and Soxhlet-extracted EMO, but their physicochemical values were lower than those of cold-pressed EMO. Cold-pressed EMO had higher oxidation stability, DPPH (1-diphenyl-2-picrylhydrazyl) and hydroxyl radical-scavenging activities than flash-extracted EMO and Soxlet extracted EMO. The flash extraction is demonstrated to be an alternative, efficient method for the vegetable oil production.

Surfactant protein D attenuates sub-epithelial fibrosis in allergic airways disease through TGF-β.

Science.gov (United States)

Ogawa, Hirohisa; Ledford, Julie G; Mukherjee, Sambuddho; Aono, Yoshinori; Nishioka, Yasuhiko; Lee, James J; Izumi, Keisuke; Hollingsworth, John W

2014-11-29

Surfactant protein D (SP-D) can regulate both innate and adaptive immunity. Recently, SP-D has been shown to contribute to the pathogenesis of airway allergic inflammation and bleomycin-induced pulmonary fibrosis. However, in allergic airways disease, the role of SP-D in airway remodeling remains unknown. The objective of this study was to determine the contribution of functional SP-D in regulating sub-epithelial fibrosis in a mouse chronic house dust mite model of allergic airways disease. C57BL/6 wild-type (WT) and SP-D-/- mice (C57BL/6 background) were chronically challenged with house dust mite antigen (Dermatophagoides pteronyssinus, Dp). Studies with SP-D rescue and neutralization of TGF-β were conducted. Lung histopathology and the concentrations of collagen, growth factors, and cytokines present in the airspace and lung tissue were determined. Cultured eosinophils were stimulated by Dp in presence or absence of SP-D. Dp-challenged SP-D-/- mice demonstrate increased sub-epithelial fibrosis, collagen production, eosinophil infiltration, TGF-β1, and IL-13 production, when compared to Dp-challenged WT mice. By immunohistology, we detected an increase in TGF-β1 and IL-13 positive eosinophils in SP-D-/- mice. Purified eosinophils stimulated with Dp produced TGF-β1 and IL-13, which was prevented by co-incubation with SP-D. Additionally, treatment of Dp challenged SP-D-/- mice with exogenous SP-D was able to rescue the phenotypes observed in SP-D-/- mice and neutralization of TGF-β1 reduced sub-epithelial fibrosis in Dp-challenged SP-D-/- mice. These data support a protective role for SP-D in the pathogenesis of sub-epithelial fibrosis in a mouse model of allergic inflammation through regulation of eosinophil-derived TGF-β.

Trisonic Gas-Dynamics Facility (TGF)

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Federal Laboratory Consortium — Description: The TGF is a two-foot square, continuous-flow, closed-circuit wind tunnel which is optimal for conducting research experiments. The facility provides a...

Role of TGF-β signaling in inherited and acquired myopathies

Directory of Open Access Journals (Sweden)

Burks Tyesha N

2011-05-01

Full Text Available Abstract The transforming growth factor-beta (TGF-β superfamily consists of a variety of cytokines expressed in many different cell types including skeletal muscle. Members of this superfamily that are of particular importance in skeletal muscle are TGF-β1, mitogen-activated protein kinases (MAPKs, and myostatin. These signaling molecules play important roles in skeletal muscle homeostasis and in a variety of inherited and acquired neuromuscular disorders. Expression of these molecules is linked to normal processes in skeletal muscle such as growth, differentiation, regeneration, and stress response. However, chronic elevation of TGF-β1, MAPKs, and myostatin is linked to various features of muscle pathology, including impaired regeneration and atrophy. In this review, we focus on the aberrant signaling of TGF-β in various disorders such as Marfan syndrome, muscular dystrophies, sarcopenia, and critical illness myopathy. We also discuss how the inhibition of several members of the TGF-β signaling pathway has been implicated in ameliorating disease phenotypes, opening up novel therapeutic avenues for a large group of neuromuscular disorders.

Flashing inception in flowing liquids

International Nuclear Information System (INIS)

Jones, O.C. Jr.

1980-01-01

The inception of net vaporization in flashing flows is examined. It is suggested that the flashing inception can be expressed as two additive effects. One is due to the static decompression which is a function of the initial temperature and also the expansion rate. The other effect which is a function of Reynolds number and flashing index, is due to the turbulent fluctuations of the flowing liquid. It is shown that by taking a three standard deviation band on the turbulent velocity fluctuations, an adequate representation of the inverse mass flux effect on flashing inception for existing data is obtained. The turbulence effects are combined with the correlation of Alamgir and Lienhard to provide predictive methods recommended for the case where both static and convective decompression effects exist

Dendrogeomorphic analysis of flash floods in a small ungauged mountain catchment (Central Spain)

Science.gov (United States)

Ruiz-Villanueva, Virginia; Díez-Herrero, Andrés; Stoffel, Markus; Bollschweiler, Michelle; Bodoque, José M.; Ballesteros, Juan A.

2010-06-01

Flash floods represent one of the most significant natural hazards with serious death tolls and economic damage at a worldwide level in general and in Mediterranean mountain catchments in particular. In these environments, systematic data is often lacking and analyses have to be based on alternative approaches such as dendrogeomorphology. In this study, we focus on the identification of flash floods based on growth disturbances (GD) observed in 98 heavily affected Mediterranean pine trees ( Pinus pinaster Ait.) located in or next to the torrential channel of the Pelayo River in the Spanish Central System. Flash floods are quite common in this catchment and are triggered by heavy storms, with high discharge and debris transport rates favoured by high stream gradients. Comparison of the anomalies in tree morphology and the position of the trees in the channel showed that the intensity of the disturbance clearly depends on geomorphology. The dating of past flash flood events was based on the number and intensity of GD observed in the tree-ring series and on the spatial distribution of affected trees along the torrent, thus allowing seven flash flood events during the last 50 years to be dated, namely in 1963, 1966, 1973, 1976, 1996, 2000, and 2005.

Fibronectin regulates the activation of THP-1 cells by TGF-beta1.

Science.gov (United States)

Wang, A C; Fu, L

2001-03-01

To determine how fibronectin regulates the immunomodulatory effects of transforming growth factor (TGF)-beta on THP-1 cells. THP-1 monocytic cell line. THP-1 cells were primed for 48 h in the presence or absence of 250 pM TGF-beta1. Assays or assessments carried out, together with statistical test applied. We found that adherence to fibronectin dramatically modulates the effects of TGF-beta1 on the human monocytic cell line THP-1. TGF-beta did not significantly affect constitutive interleukin (IL)-8 secretion or IL-1beta-induced IL-8 secretion from suspended cells. In contrast, TGF-beta stimulated IL-8 secretion as well as augmented IL-1beta-induced IL-8 secretion from adherent cells. The differential effects of TGF-beta1 on IL-8 secretion from suspended and adherent cells could not be explained by differences in IL-1 receptor antagonist production. The effects of fibronectin on TGF-beta1 induced IL-8 secretion from THP-1 cells were mimicked by adhesion to immobilized anti-a4beta1 integrin antibody and to a fibronectin fragment containing the CS-1 domain. These results indicate that alpha4beta1-mediated adhesion to fibronectin may play a key role during inflammation by profoundly influencing the effects of TGF-beta1 on monocytes.

TGF-β1 of no avail as prognostic marker in lyme disease

Directory of Open Access Journals (Sweden)

Julia Schumann

2014-05-01

Full Text Available Background. Within the present in vivo study using the wild type mouse strains C3H/HeN and FVB/N it was intended to (1 measure TGF-β1 expression in the course of lyme disease, (2 examine the potential correlation of TGF-β1 expression with the clinical outcome of a Borrelia infection (with a focus on lyme arthritis, (3 develop a diagnostic tool based on the endogenous factor TGF-β1 to predict the progressivity of lyme disease.Findings. In the course of lyme disease there was an increase in the serum content of active TGF-β1, which became significant 56 days post infection (p < 0.001. The serum concentration of total TGF-β1 in the course of infection initially decreased then rebounded and subsequently dropped again. Despite considerable individual variations in active TGF-β1 serum concentrations there were no identifiable dissimilarities in the clinical appearance of the mice. Likewise, no correlation could be seen between the serum content of active TGF-β1 and the severity of lyme arthritis of tibiotarsal joints of infected mice.Conclusions. The present study clearly shows that TGF-β1 is of no avail as prognostic marker in lyme disease. Hence, the search for an endogenous predictive factor, which can be determined in an easy and reliable manner, remains open.

GeckoFTL: Scalable Flash Translation Techniques For Very Large Flash Devices

DEFF Research Database (Denmark)

Dayan, Niv; Bonnet, Philippe; Idreos, Stratos

2016-01-01

The volume of metadata needed by a flash translation layer (FTL) is proportional to the storage capacity of a flash device. Ideally, this metadata should reside in the device's integrated RAM to enable fast access. However, as flash devices scale to terabytes, the necessary volume of metadata...... thereby harming performance and device lifetime. In this paper, we identify a key component of the metadata called the Page Validity Bitmap (PVB) as the bottleneck. PVB is used by the garbage-collectors of state-of-the-art FTLs to keep track of which physical pages in the device are invalid. PVB...... constitutes 95% of the FTL's RAM-resident metadata, and recovering PVB after power fails takes a significant proportion of the overall recovery time. To solve this problem, we propose a page-associative FTL called GeckoFTL, whose central innovation is replacing PVB with a new data structure called Logarithmic...

An Analysis of Total Lightning Flash Rates Over Florida

Science.gov (United States)

Mazzetti, Thomas O.; Fuelberg, Henry E.

2017-12-01

Although Florida is known as the "Sunshine State", it also contains the greatest lightning flash densities in the United States. Flash density has received considerable attention in the literature, but lightning flash rate has received much less attention. We use data from the Earth Networks Total Lightning Network (ENTLN) to produce a 5 year (2010-2014) set of statistics regarding total flash rates over Florida and adjacent regions. Instead of tracking individual storms, we superimpose a 0.2° × 0.2° grid over the study region and count both cloud-to-ground (CG) and in-cloud (IC) flashes over 5 min intervals. Results show that the distribution of total flash rates is highly skewed toward small values, whereas the greatest rate is 185 flashes min-1. Greatest average annual flash rates ( 3 flashes min-1) are located near Orlando. The southernmost peninsula, North Florida, and the Florida Panhandle exhibit smaller average annual flash rates ( 1.5 flashes min-1). Large flash rates > 100 flashes min-1 can occur during any season, at any time during the 24 h period, and at any location within the domain. However, they are most likely during the afternoon and early evening in East Central Florida during the spring and summer months.

Molecular Cloning and Expression Analysis of Transforming Growth Factor TGF-β1 and TGF-β3 in Half-smooth Tongue Sole (Cynoglossus semilaevis) Following Stimulation with Vibrio harveyi%半滑舌鳎转化生长因子TGF-β1和TGF-β3基因的克隆及受哈维氏弧菌感染后表达分析

Institute of Scientific and Technical Information of China (English)

李雪; 陈松林; 杨长庚; 邵长伟; 李仰真; 位战飞

2016-01-01

转化生长因子β (transforming growth factor β,TGF-β)是一类具有多种功能的蛋白超家族,在细胞免疫、细胞增殖分化和组织损伤的修复中起着关键性作用.本研究从半滑舌鳎(Cynoglossus semilaevis)肝脏中克隆获得了TGF-β1和TGF-β3基因.推导的TGF-β1和TGF-β3氨基酸序列均含有多个N糖基化位点和一个TGF-β家族标签.系统进化树分析显示,半滑舌鳎TG F-β1和TGF-β3分别与鱼类的TGF-β1和TGF-β3亲缘关系最为密切.qRT-PCR结果表明,半滑舌鳎TGF-β1和TGF-β3基因在健康鱼的多个组织中均有表达,二者在皮肤中表达量最高,在肌肉中表达量最低.经哈维氏弧菌(Vibrio harveyi)感染后,TGF-β1在肝脏、脾脏和肾脏中呈现先上升后下降的表达趋势,在感染48 h后的肝脏中表达量达到最大值,是对照组的3.17倍;TGF-β3在脾脏、肾脏和鳃中也呈现先上升后下降的表达趋势,在感染24 h后的鳃中表达量达到最大值,是对照组的4.71倍.以上结果提示,TG F-β1和TGF-β3可能在半滑舌鳎抵御细菌感染的免疫中发挥了重要作用,本研究为证明二者参与机体免疫调节提供了有力证据,为半滑舌鳎分子免疫研究提供了理论依据.

Flash CS4: The Missing Manual

CERN Document Server

Grover, Chris

2008-01-01

Unlock the power of Flash and bring gorgeous animations to life onscreen. Flash CS4: The Missing Manual includes a complete primer on animation, a guided tour of the program's tools and capabilities, lots of new illustrations, and more details on working with video. Beginners will learn to use the software in no time, and experienced Flash designers will improve their skills.

Altered TGF-β endocytic trafficking contributes to the increased signaling in Marfan syndrome.

Science.gov (United States)

Siegert, Anna-Maria; Serra-Peinado, Carla; Gutiérrez-Martínez, Enric; Rodríguez-Pascual, Fernando; Fabregat, Isabel; Egea, Gustavo

2018-02-01

The main cardiovascular alteration in Marfan syndrome (MFS) is the formation of aortic aneurysms in which augmented TGF-β signaling is reported. However, the primary role of TGF-β signaling as a molecular link between the genetic mutation of fibrillin-1 and disease onset is controversial. The compartmentalization of TGF-β endocytic trafficking has been shown to determine a signaling response in which clathrin-dependent internalization leads to TGF-β signal propagation, and caveolin-1 (CAV-1) associated internalization leads to signal abrogation. We here studied the contribution of endocytic trafficking compartmentalization to increased TGF-β signaling in vascular smooth muscle cells (VSMC) from MFS patients. We examined molecular components involved in clathrin- (SARA, SMAD2) and caveolin-1- (SMAD7, SMURF2) dependent endocytosis. Marfan VSMC showed higher recruitment of SARA and SMAD2 to membranes and their increased interaction with TGF-β receptor II, as well as higher colocalization of SARA with the early endosome marker EEA1. We assessed TGF-β internalization using a biotinylated ligand (b-TGF-β), which colocalized equally with either EEA1 or CAV-1 in VSMC from Marfan patients and controls. However, in Marfan cells, colocalization of b-TGF-β with SARA and EEA1 was increased and accompanied by decreased colocalization with CAV-1 at EEA1-positive endosomes. Moreover, Marfan VSMC showed higher transcriptional levels and membrane enrichment of RAB5. Our results indicate that increased RAB5-associated SARA localization to early endosomes facilitates its TGF-β receptor binding and phosphorylation of signaling mediator SMAD2 in Marfan VSMC. This is accompanied by a reduction of TGF-β sorting into multifunctional vesicles containing cargo from both internalization pathways. Copyright © 2017 Elsevier B.V. All rights reserved.

X-RAY AND GAMMA-RAY FLASHES FROM TYPE Ia SUPERNOVAE?

International Nuclear Information System (INIS)

Hoeflich, Peter; Schaefer, Bradley E.

2009-01-01

We investigate two potential mechanisms that will produce X-ray and γ-ray flashes from Type Ia supernovae (SN-Ia). The first mechanism is the breakout of the thermonuclear burning front as it reaches the surface of the white dwarf (WD). The second mechanism is the interaction of the rapidly expanding envelope with material within an accretion disk in the progenitor system. Our study is based on the delayed detonation scenario because this can account for the majority of light curves, spectra, and statistical properties of 'Branch-normal' SN-Ia. Based on detailed radiation-hydro calculations which include nuclear networks, we find that both mechanisms produce brief flashes of high-energy radiation with peak luminosities of 10 48 -10 50 erg s -1 . The breakout from the WD surface produces flashes with a rapid exponential decay by 3-4 orders of magnitude on timescales of a few tenths of a second and with most of the radiation in the X-ray and soft γ-ray range. The shocks produced in gases in and around the binary will produce flashes with a characteristic duration of a few seconds with most of the radiation coming out as X-rays and γ-rays. In both mechanisms, we expect a fast rise and slow decline and, after the peak, an evolution from hard to softer radiation due to adiabatic expansion. In many cases, flashes from both mechanisms will be superposed. The X- and γ-ray visibility of an SN-Ia will depend strongly on self-absorption within the progenitor system, specifically on the properties of the accretion disk and its orientation toward the observer. Such X-ray and γ-ray flashes could be detected as triggered events by gamma-ray burst (GRB) detectors on satellites, with events in current GRB catalogs. We have searched through the GRB catalogs (for the BATSE, HETE, and Swift experiments) for GRBs that occur at the extrapolated time of explosion and in the correct direction for known Type Ia supernovae with radial velocity of less than 3000 km s -1 . For the Burst

Attenuation of CCl4-induced hepatic fibrosis in mice by vaccinating against TGF-β1.

Directory of Open Access Journals (Sweden)

Xiaobao Fan

Full Text Available Transforming growth factor β1 (TGF-β1 is the pivotal pro-fibrogenic cytokine in hepatic fibrosis. Reducing the over-produced expression of TGF-β1 or blocking its signaling pathways is considered to be a promising therapeutic strategy for hepatic fibrosis. In this study, we evaluated the feasibility of attenuating hepatic fibrosis by vaccination against TGF-β1 with TGF-β1 kinoids. Two TGF-β1 kinoid vaccines were prepared by cross-linking TGF-β1-derived polypeptides (TGF-β1(25-[41-65] and TGF-β1(30-[83-112] to keyhole limpet hemocyanin (KLH. Immunization with the two TGF-β1 kinoids efficiently elicited the production of high-levels of TGF-β1-specific antibodies against in BALB/c mice as tested by enzyme-linked immunosorbent assay (ELISA and Western blotting. The antisera neutralized TGF-β1-induced growth-inhibition on mink lung epithelial cells (Mv1Lu and attenuated TGF-β1-induced Smad2/3 phosphorylation, α-SMA, collagen type 1 alpha 2 (COL1A2, plasminogen activator inhibitor-1 (PAI-1 and tissue inhibitor of metalloproteinase-1 (TIMP-1 expression in the rat hepatic stellate cell (HSC line, HSC-T6. Vaccination against TGF-β1 with the kinoids significantly suppressed CCl4-induced collagen deposition and the expression of α-SMA and desmin, attenuated hepatocyte apoptosis and accelerated hepatocyte proliferation in BALB/c mice. These results demonstrated that immunization with the TGF-β1 kinoids efficiently attenuated CCl4-induced hepatic fibrosis and liver injury. Our study suggests that vaccination against TGF-β1 might be developed into a feasible therapeutic approach for the treatment of chronic fibrotic liver diseases.

Emergence, development and diversification of the TGF-β signalling pathway within the animal kingdom

Directory of Open Access Journals (Sweden)

Moustakas Aristidis

2009-02-01

Full Text Available Abstract Background The question of how genomic processes, such as gene duplication, give rise to co-ordinated organismal properties, such as emergence of new body plans, organs and lifestyles, is of importance in developmental and evolutionary biology. Herein, we focus on the diversification of the transforming growth factor-β (TGF-β pathway – one of the fundamental and versatile metazoan signal transduction engines. Results After an investigation of 33 genomes, we show that the emergence of the TGF-β pathway coincided with appearance of the first known animal species. The primordial pathway repertoire consisted of four Smads and four receptors, similar to those observed in the extant genome of the early diverging tablet animal (Trichoplax adhaerens. We subsequently retrace duplications in ancestral genomes on the lineage leading to humans, as well as lineage-specific duplications, such as those which gave rise to novel Smads and receptors in teleost fishes. We conclude that the diversification of the TGF-β pathway can be parsimoniously explained according to the 2R model, with additional rounds of duplications in teleost fishes. Finally, we investigate duplications followed by accelerated evolution which gave rise to an atypical TGF-β pathway in free-living bacterial feeding nematodes of the genus Rhabditis. Conclusion Our results challenge the view of well-conserved developmental pathways. The TGF-β signal transduction engine has expanded through gene duplication, continually adopting new functions, as animals grew in anatomical complexity, colonized new environments, and developed an active immune system.

TGF-β-activated kinase 1 (TAK1 signaling regulates TGF-β-induced WNT-5A expression in airway smooth muscle cells via Sp1 and β-catenin.

Directory of Open Access Journals (Sweden)

Kuldeep Kumawat

Full Text Available WNT-5A, a key player in embryonic development and post-natal homeostasis, has been associated with a myriad of pathological conditions including malignant, fibroproliferative and inflammatory disorders. Previously, we have identified WNT-5A as a transcriptional target of TGF-β in airway smooth muscle cells and demonstrated its function as a mediator of airway remodeling. Here, we investigated the molecular mechanisms underlying TGF-β-induced WNT-5A expression. We show that TGF-β-activated kinase 1 (TAK1 is a critical mediator of WNT-5A expression as its pharmacological inhibition or siRNA-mediated silencing reduced TGF-β induction of WNT-5A. Furthermore, we show that TAK1 engages p38 and c-Jun N-terminal kinase (JNK signaling which redundantly participates in WNT-5A induction as only simultaneous, but not individual, inhibition of p38 and JNK suppressed TGF-β-induced WNT-5A expression. Remarkably, we demonstrate a central role of β-catenin in TGF-β-induced WNT-5A expression. Regulated by TAK1, β-catenin is required for WNT-5A induction as its silencing repressed WNT-5A expression whereas a constitutively active mutant augmented basal WNT-5A abundance. Furthermore, we identify Sp1 as the transcription factor for WNT-5A and demonstrate its interaction with β-catenin. We discover that Sp1 is recruited to the WNT-5A promoter in a TGF-β-induced and TAK1-regulated manner. Collectively, our findings describe a TAK1-dependent, β-catenin- and Sp1-mediated signaling cascade activated downstream of TGF-β which regulates WNT-5A induction.

Drak2 Does Not Regulate TGF-β Signaling in T Cells.

Directory of Open Access Journals (Sweden)

Tarsha L Harris

Full Text Available Drak2 is a serine/threonine kinase expressed highest in T cells and B cells. Drak2-/- mice are resistant to autoimmunity in mouse models of type 1 diabetes and multiple sclerosis. Resistance to these diseases occurs, in part, because Drak2 is required for the survival of autoreactive T cells that induce disease. However, the molecular mechanisms by which Drak2 affects T cell survival and autoimmunity are not known. A recent report demonstrated that Drak2 negatively regulated transforming growth factor-β (TGF-β signaling in tumor cell lines. Thus, increased TGF-β signaling in the absence of Drak2 may contribute to the resistance to autoimmunity in Drak2-/- mice. Therefore, we examined if Drak2 functioned as a negative regulator of TGF-β signaling in T cells, and whether the enhanced susceptibility to death of Drak2-/- T cells was due to augmented TGF-β signaling. Using several in vitro assays to test TGF-β signaling and T cell function, we found that activation of Smad2 and Smad3, which are downstream of the TGF-β receptor, was similar between wildtype and Drak2-/- T cells. Furthermore, TGF-β-mediated effects on naïve T cell proliferation, activated CD8+ T cell survival, and regulatory T cell induction was similar between wildtype and Drak2-/- T cells. Finally, the increased susceptibility to death in the absence of Drak2 was not due to enhanced TGF-β signaling. Together, these data suggest that Drak2 does not function as a negative regulator of TGF-β signaling in primary T cells stimulated in vitro. It is important to investigate and discern potential molecular mechanisms by which Drak2 functions in order to better understand the etiology of autoimmune diseases, as well as to validate the use of Drak2 as a target for therapeutic treatment of these diseases.

Arctigenin represses TGF-β-induced epithelial mesenchymal transition in human lung cancer cells.

Science.gov (United States)

Xu, Yanrui; Lou, Zhiyuan; Lee, Seong-Ho

2017-11-18

Arctigenin (ARC) is a lignan that is abundant in Asteraceae plants, which show anti-inflammatory and anti-cancer activities. The current study investigated whether ARC affects cancer progression and metastasis, focusing on EMT using invasive human non-small cell lung cancer (NSCLC) cells. No toxicity was observed in the cells treated with different doses of ARC (12-100 μM). The treatment of ARC repressed TGF-β-stimulated changes of metastatic morphology and cell invasion and migration. ARC inhibited TGF-β-induced phosphorylation and transcriptional activity of smad2/3, and expression of snail. ARC also decreased expression of N-cadherin and increased expression of E-cadherin in dose-dependent and time-dependent manners. These changes were accompanied by decreased amount of phospho-smad2/3 in nucleus and nuclear translocation of smad2/3. Moreover, ARC repressed TGF-β-induced phosphorylation of ERK and transcriptional activity of β-catenin. Our data demonstrate anti-metastatic activity of ARC in lung cancer model. Copyright © 2017 Elsevier Inc. All rights reserved.

PENGEMBANGAN MEDIA FLASH BERBASIS PEMBELAJARAN INKUIRI UNTUK MENINGKATKAN HASIL BELAJAR SISWA

Directory of Open Access Journals (Sweden)

Indah Triana Aprillia

2016-01-01

Full Text Available Penelitian ini merupakan penelitian Research and Development (R&D. Tahapan rancangan pengembangan media flash ini menggunakan langkah prosedural oleh Borg and Gall. Tujuan penelitian ini adalah untuk mengetahui keefektifan pada ranah kognitif, afektif dan psikomotorik dalam penggunaan media flash berbasis pembelajaran inkuiri. Pengumpulan data pada penelitian ini menggunakan metode observasi, tes, angket dan dokumentasi. Data hasil penelitian dianalisis menggunakan metode analisis deskriptif kuantitatif. Produk pengembangan dinyatakan valid dan layak apabila telah memenuhi kriteria baik atau sangat baik dari validator. Produk pengembangan teruji untuk meningkatkan hasil belajar siswa yaitu diuji berdasarkan penggunaan media flash pada proses pembelajaran. Hasil pengembangan produk media flash berbasis pembelajaran inkuiri dinyatakan valid dengan kategori baik dan layak diterapkan berdasarkan uji kelayakan oleh ahli media dan ahli materi dengan skor rata-rata ahli media 73.5 dan ahli materi 37. Media flash dinyatakan efektif karena 36 siswa mencapai nilai KKM pada hasil tes, dengan nilai n-gain 0,71 dan pada aspek afektif dan psikomotorik termasuk dalam kategori baik, serta mendapat respon positif dari penggunanya dilihat dari angket tanggapan siswa, sehingga media flash efektif meningkatkan hasil belajar siswa. The research include in Research and Development (R&D. This step of flash media development uses procedural step by Borg and Gall. The purpose of this research is to know the effectiveness in the cognitive, afective, and psychomotoric domain in using flash media based on inquiry learning. Data accumulation in this research uses observation, test, questionaire and documentation methods. The result data of this research is analyzed by using quantitative descriptive analysis method. Development product is called valid and proper if it has fullfilled good or very good criteria from the validator. The development product proved to improve the

Flash flood modeling with the MARINE hydrological distributed model

Science.gov (United States)

Estupina-Borrell, V.; Dartus, D.; Ababou, R.

2006-11-01

Flash floods are characterized by their violence and the rapidity of their occurrence. Because these events are rare and unpredictable, but also fast and intense, their anticipation with sufficient lead time for warning and broadcasting is a primary subject of research. Because of the heterogeneities of the rain and of the behavior of the surface, spatially distributed hydrological models can lead to a better understanding of the processes and so on they can contribute to a better forecasting of flash flood. Our main goal here is to develop an operational and robust methodology for flash flood forecasting. This methodology should provide relevant data (information) about flood evolution on short time scales, and should be applicable even in locations where direct observations are sparse (e.g. absence of historical and modern rainfalls and streamflows in small mountainous watersheds). The flash flood forecast is obtained by the physically based, space-time distributed hydrological model "MARINE'' (Model of Anticipation of Runoff and INondations for Extreme events). This model is presented and tested in this paper for a real flash flood event. The model consists in two steps, or two components: the first component is a "basin'' flood module which generates flood runoff in the upstream part of the watershed, and the second component is the "stream network'' module, which propagates the flood in the main river and its subsidiaries. The basin flash flood generation model is a rainfall-runoff model that can integrate remotely sensed data. Surface hydraulics equations are solved with enough simplifying hypotheses to allow real time exploitation. The minimum data required by the model are: (i) the Digital Elevation Model, used to calculate slopes that generate runoff, it can be issued from satellite imagery (SPOT) or from French Geographical Institute (IGN); (ii) the rainfall data from meteorological radar, observed or anticipated by the French Meteorological Service (M�

TGF-β1 accelerates the DNA damage response in epithelial cells via Smad signaling

Energy Technology Data Exchange (ETDEWEB)

Lee, Jeeyong; Kim, Mi-Ra; Kim, Hyun-Ji; An, You Sun; Yi, Jae Youn, E-mail: yjy_71@kcch.re.kr

2016-08-05

The evidence suggests that transforming growth factor-beta (TGF-β) regulates the DNA-damage response (DDR) upon irradiation, and we previously reported that TGF-β1 induced DNA ligase IV (Lig4) expression and enhanced the nonhomologous end-joining repair pathway in irradiated cells. In the present study, we investigated the effects of TGF-β1 on the irradiation-induced DDRs of A431 and HaCaT cells. Cells were pretreated with or without TGF-β1 and irradiated. At 30 min post-irradiation, DDRs were detected by immunoblotting of phospho-ATM, phospho-Chk2, and the presence of histone foci (γH2AX). The levels of all three factors were similar right after irradiation regardless of TGF-β1 pretreatment. However, they soon thereafter exhibited downregulation in TGF-β1-pretreated cells, indicating the acceleration of the DDR. Treatment with a TGF-β type I receptor inhibitor (SB431542) or transfections with siRNAs against Smad2/3 or DNA ligase IV (Lig4) reversed this acceleration of the DDR. Furthermore, the frequency of irradiation-induced apoptosis was decreased by TGF-β1 pretreatment in vivo, but this effect was abrogated by SB431542. These results collectively suggest that TGF-β1 could enhance cell survival by accelerating the DDR via Smad signaling and Lig4 expression. -- Highlights: •TGF-β1 pretreatment accelerates γ-radiation-induced DNA damage response. •TGF-β1-accelerated DNA damage response is dependent on Smad signaling and DNA Ligase IV. •TGF-β1 pretreatment protects epithelial cells from γ-radiation in vivo.

Ultra-Fast Flash Observatory for the observation of early photons from gamma-ray bursts

DEFF Research Database (Denmark)

Park, I H; Brandt, Søren; Budtz-Jørgensen, Carl

2013-01-01

One of the least documented and understood aspects of gamma-ray bursts (GRBs) is the rise phase of the optical light curve. The Ultra-Fast Flash Observatory (UFFO) is an effort to address this question through extraordinary opportunities presented by a series of space missions including a small s...

Ultra-Fast Flash Observatory (uffo) for Observation of Early Photons from Gamma Ray Bursts

DEFF Research Database (Denmark)

Park, I. H.; Ahmad, S.; Barrillon, P.

2013-01-01

One of the least documented and understood aspects of gamma-ray bursts (GRB) is the rise phase of the optical light curve. The Ultra-Fast Flash Observatory (UFFO) is an effort to address this question through extraordinary opportunities presented by a series of space missions including a small sp...

Flashing coupled density wave oscillation

International Nuclear Information System (INIS)

Jiang Shengyao; Wu Xinxin; Zhang Youjie

1997-07-01

The experiment was performed on the test loop (HRTL-5), which simulates the geometry and system design of the 5 MW reactor. The phenomenon and mechanism of different kinds of two-phase flow instabilities, namely geyser instability, flashing instability and flashing coupled density wave instability are described. The especially interpreted flashing coupled density wave instability has never been studied well, it is analyzed by using a one-dimensional non-thermo equilibrium two-phase flow drift model computer code. Calculations are in good agreement with the experiment results. (5 refs.,5 figs., 1 tab.)

Effect of rat ovary irradiation or OVX on the expression of COLI and TGF-β1 mRNA in the rat bone

International Nuclear Information System (INIS)

Gao Yanhong; Gao Jianjun; Jin Weifang; Wang Hongfu

2003-01-01

To observe the effects of exposure of rat ovary to radiation or OVX on the expression of TGF-β 1 and COLI in the rat bone. The mRNA levels of TGF-β 1 and COLI in rat tibiae were measured with RT-PCR after the rat ovaries were irradiated by 50 Gy of 137 Cs γ-rays or OVX. For both the radiation group and the OVX group, the COLI mRNA level in the rat bone increased, whereas the TGF-β 1 decreased. Irradiation of ovary and OVX affect the expression of COLI and TGF-β 1 mRNA in bone probably in a similar way which is related to estrogen decrease

Flash CS5 The Missing Manual

CERN Document Server

Grover, Chris

2010-01-01

Once you know how to use Flash, you can create everything from simple animations to high-end desktop applications, but it's a complex tool that can be difficult to master on your own-unless you have this Missing Manual. This book will help you learn all you need to know about Flash CS5 to create animations that bring your ideas to life. Learn animation basics. Find everything you need to know to get started with FlashMaster the Flash tools. Learn the animation and effects toolset, with clear explanations and hands-on examplesUse 3D effects. Rotate and put objects in motion in three dimensions

The antifibrotic effects of TGF-β1 siRNA on hepatic fibrosis in rats

International Nuclear Information System (INIS)

Lang, Qing; Liu, Qi; Xu, Ning; Qian, Ke-Li; Qi, Jing-Hu; Sun, Yin-Chun; Xiao, Lang; Shi, Xiao-Feng

2011-01-01

Highlights: → We constructed CCL4 induced liver fibrosis model successfully. → We proofed that the TGF-β1 siRNA had a definite therapy effect to CCL4 induced liver fibrosis. → The therapy effect of TGF-β1 siRNA had dose-dependent. -- Abstract: Background/aims: Hepatic fibrosis results from the excessive secretion of matrix proteins by hepatic stellate cells (HSCs), which proliferate during fibrotic liver injury. Transforming growth factor (TGF)-β1 is the dominant stimulus for extracellular matrix (ECM) production by stellate cells. Our study was designed to investigate the antifibrotic effects of using short interference RNA (siRNA) to target TGF-β1 in hepatic fibrosis and its mechanism in rats exposed to a high-fat diet and carbon tetrachloride (CCL4). Methods: A total of 40 healthy, male SD (Sprague-Dawley) rats were randomly divided into five even groups containing of eight rats each: normal group, model group, TGF-β1 siRNA 0.125 mg/kg treatment group, TGF-β1 siRNA 0.25 mg/kg treatment group and TGF-β1 siRNA negative control group (0.25 mg/kg). CCL4 and a high-fat diet were used for 8 weeks to induce hepatic fibrosis. All the rats were then sacrificed to collect liver tissue samples. A portion of the liver samples were soaked in formalin for Hematoxylin-Eosin staining, classifying the degree of liver fibrosis, and detecting the expression of type I and III collagen and TGF-β1; the remaining liver samples were stored in liquid nitrogen to be used for detecting TGF-β1 by Western blotting and for measuring the mRNA expression of type I and III collagen and TGF-β1 by quantitative real-time polymerase chain reaction. Results: Comparing the TGF-β1 siRNA 0.25 mg/kg treatment group to the model group, the TGF-β1 siRNA negative control group and the TGF-β1 siRNA 0.125 mg/kg treatment group showed significantly reduced levels of pathological changes, protein expression and the mRNA expression of TGF-β1, type I collagen and type III collagen (P < 0

The antifibrotic effects of TGF-{beta}1 siRNA on hepatic fibrosis in rats

Energy Technology Data Exchange (ETDEWEB)

Lang, Qing; Liu, Qi [Key Laboratory of Molecular Biology for Infectious Diseases, Ministry of Education, Instituted for Virus Hepatitis and Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing (China); Xu, Ning [The Second Hospital of YuLin, Shanxi Province (China); Qian, Ke-Li; Qi, Jing-Hu; Sun, Yin-Chun; Xiao, Lang [Key Laboratory of Molecular Biology for Infectious Diseases, Ministry of Education, Instituted for Virus Hepatitis and Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing (China); Shi, Xiao-Feng, E-mail: sxff2003@yahoo.com.cn [Key Laboratory of Molecular Biology for Infectious Diseases, Ministry of Education, Instituted for Virus Hepatitis and Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing (China)

2011-06-10

Highlights: {yields} We constructed CCL4 induced liver fibrosis model successfully. {yields} We proofed that the TGF-{beta}1 siRNA had a definite therapy effect to CCL4 induced liver fibrosis. {yields} The therapy effect of TGF-{beta}1 siRNA had dose-dependent. -- Abstract: Background/aims: Hepatic fibrosis results from the excessive secretion of matrix proteins by hepatic stellate cells (HSCs), which proliferate during fibrotic liver injury. Transforming growth factor (TGF)-{beta}1 is the dominant stimulus for extracellular matrix (ECM) production by stellate cells. Our study was designed to investigate the antifibrotic effects of using short interference RNA (siRNA) to target TGF-{beta}1 in hepatic fibrosis and its mechanism in rats exposed to a high-fat diet and carbon tetrachloride (CCL4). Methods: A total of 40 healthy, male SD (Sprague-Dawley) rats were randomly divided into five even groups containing of eight rats each: normal group, model group, TGF-{beta}1 siRNA 0.125 mg/kg treatment group, TGF-{beta}1 siRNA 0.25 mg/kg treatment group and TGF-{beta}1 siRNA negative control group (0.25 mg/kg). CCL4 and a high-fat diet were used for 8 weeks to induce hepatic fibrosis. All the rats were then sacrificed to collect liver tissue samples. A portion of the liver samples were soaked in formalin for Hematoxylin-Eosin staining, classifying the degree of liver fibrosis, and detecting the expression of type I and III collagen and TGF-{beta}1; the remaining liver samples were stored in liquid nitrogen to be used for detecting TGF-{beta}1 by Western blotting and for measuring the mRNA expression of type I and III collagen and TGF-{beta}1 by quantitative real-time polymerase chain reaction. Results: Comparing the TGF-{beta}1 siRNA 0.25 mg/kg treatment group to the model group, the TGF-{beta}1 siRNA negative control group and the TGF-{beta}1 siRNA 0.125 mg/kg treatment group showed significantly reduced levels of pathological changes, protein expression and the m

Akt interacts directly with Smad3 to regulate the sensitivity to TGF-beta induced apoptosis.

Science.gov (United States)

Conery, Andrew R; Cao, Yanna; Thompson, E Aubrey; Townsend, Courtney M; Ko, Tien C; Luo, Kunxin

2004-04-01

Transforming growth factor beta (TGF-beta) induces both apoptosis and cell-cycle arrest in some cell lines, but only growth arrest in others. It is not clear how this differential response to TGF-beta is specified. Smad proteins are critical mediators of TGF-beta signalling. After stimulation by TGF-beta, Smad2 and Smad3 become phosphorylated by the activated TGF-beta receptor kinases, oligomerize with Smad4, translocate to the nucleus and regulate the expression of TGF-beta target genes. Here we report that the sensitivity to TGF-beta induced apoptosis is regulated by crosstalk between the Akt/PKB serine/threonine kinase and Smad3 through a mechanism that is independent of Akt kinase activity. Akt interacts directly with unphosphorylated Smad3 to sequester it outside the nucleus, preventing its phosphorylation and nuclear translocation. This results in inhibition of Smad3-mediated transcription and apoptosis. Furthermore, the ratio of Smad3 to Akt correlates with the sensitivity of cells to TGF-beta induced apoptosis. Alteration of this ratio changes the apoptotic, but not the growth-inhibitory, responses of cells to TGF-beta. These findings identify an important determinant of sensitivity to TGF-beta-induced apoptosis that involves crosstalk between the TGF-beta and phosphatidylinositol-3-OH kinase (PI(3)K) pathways.

A Durable Flash Memory Search Tree

OpenAIRE

Clay III, James; Wortman, Kevin

2012-01-01

We consider the task of optimizing the B-tree data structure, used extensively in operating systems and databases, for sustainable usage on multi-level flash memory. Empirical evidence shows that this new flash memory tree, or FM Tree, extends the operational lifespan of each block of flash memory by a factor of roughly 27 to 70 times, while still supporting logarithmic-time search tree operations.

Role of TGF-β in a mouse model of high turnover renal osteodystrophy.

Science.gov (United States)

Liu, Shiguang; Song, Wenping; Boulanger, Joseph H; Tang, Wen; Sabbagh, Yves; Kelley, Brian; Gotschall, Russell; Ryan, Susan; Phillips, Lucy; Malley, Katie; Cao, Xiaohong; Xia, Tai-He; Zhen, Gehua; Cao, Xu; Ling, Hong; Dechow, Paul C; Bellido, Teresita M; Ledbetter, Steven R; Schiavi, Susan C

2014-01-01

Altered bone turnover is a key pathologic feature of chronic kidney disease-mineral and bone disorder (CKD-MBD). Expression of TGF-β1, a known regulator of bone turnover, is increased in bone biopsies from individuals with CKD. Similarly, TGF-β1 mRNA and downstream signaling is increased in bones from jck mice, a model of high-turnover renal osteodystrophy. A neutralizing anti-TGF-β antibody (1D11) was used to explore TGF-β's role in renal osteodystrophy. 1D11 administration to jck significantly attenuated elevated serum osteocalcin and type I collagen C-telopeptides. Histomorphometric analysis indicated that 1D11 administration increased bone volume and suppressed the elevated bone turnover in a dose-dependent manner. These effects were associated with reductions in osteoblast and osteoclast surface areas. Micro-computed tomography (µCT) confirmed the observed increase in trabecular bone volume and demonstrated improvements in trabecular architecture and increased cortical thickness. 1D11 administration was associated with significant reductions in expression of osteoblast marker genes (Runx2, alkaline phosphatase, osteocalcin) and the osteoclast marker gene, Trap5. Importantly, in this model, 1D11 did not improve kidney function or reduce serum parathyroid hormone (PTH) levels, indicating that 1D11 effects on bone are independent of changes in renal or parathyroid function. 1D11 also significantly attenuated high-turnover bone disease in the adenine-induced uremic rat model. Antibody administration was associated with a reduction in pSMAD2/SMAD2 in bone but not bone marrow as assessed by quantitative immunoblot analysis. Immunostaining revealed pSMAD staining in osteoblasts and osteocytes but not osteoclasts, suggesting 1D11 effects on osteoclasts may be indirect. Immunoblot and whole genome mRNA expression analysis confirmed our previous observation that repression of Wnt/β-catenin expression in bone is correlated with increased osteoclast activity in jck

Extracellular Matrix (ECM) Multilayer Membrane as a Sustained Releasing Growth Factor Delivery System for rhTGF-β3 in Articular Cartilage Repair

Science.gov (United States)

Park, Sang-Hyug; Kim, Moon Suk; Kim, Young Jick; Choi, Byung Hyune; Lee, Chun Tek; Park, So Ra; Min, Byoung-Hyun

2016-01-01

Recombinant human transforming growth factor beta-3 (rhTGF-β3) is a key regulator of chondrogenesis in stem cells and cartilage formation. We have developed a novel drug delivery system that continuously releases rhTGF-β3 using a multilayered extracellular matrix (ECM) membrane. We hypothesize that the sustained release of rhTGF-β3 could activate stem cells and result in enhanced repair of cartilage defects. The properties and efficacy of the ECM multilayer-based delivery system (EMLDS) are investigated using rhTGF-β3 as a candidate drug. The bioactivity of the released rhTGF-ß3 was evaluated through chondrogenic differentiation of mesenchymal stem cells (MSCs) using western blot and circular dichroism (CD) analyses in vitro. The cartilage reparability was evaluated through implanting EMLDS with endogenous and exogenous MSC in both in vivo and ex vivo models, respectively. In the results, the sustained release of rhTGF-ß3 was clearly observed over a prolonged period of time in vitro and the released rhTGF-β3 maintained its structural stability and biological activity. Successful cartilage repair was also demonstrated when rabbit MSCs were treated with rhTGF-β3-loaded EMLDS ((+) rhTGF-β3 EMLDS) in an in vivo model and when rabbit chondrocytes and MSCs were treated in ex vivo models. Therefore, the multilayer ECM membrane could be a useful drug delivery system for cartilage repair. PMID:27258120

Extracellular Matrix (ECM Multilayer Membrane as a Sustained Releasing Growth Factor Delivery System for rhTGF-β3 in Articular Cartilage Repair.

Directory of Open Access Journals (Sweden)

Soon Sim Yang

Full Text Available Recombinant human transforming growth factor beta-3 (rhTGF-β3 is a key regulator of chondrogenesis in stem cells and cartilage formation. We have developed a novel drug delivery system that continuously releases rhTGF-β3 using a multilayered extracellular matrix (ECM membrane. We hypothesize that the sustained release of rhTGF-β3 could activate stem cells and result in enhanced repair of cartilage defects. The properties and efficacy of the ECM multilayer-based delivery system (EMLDS are investigated using rhTGF-β3 as a candidate drug. The bioactivity of the released rhTGF-ß3 was evaluated through chondrogenic differentiation of mesenchymal stem cells (MSCs using western blot and circular dichroism (CD analyses in vitro. The cartilage reparability was evaluated through implanting EMLDS with endogenous and exogenous MSC in both in vivo and ex vivo models, respectively. In the results, the sustained release of rhTGF-ß3 was clearly observed over a prolonged period of time in vitro and the released rhTGF-β3 maintained its structural stability and biological activity. Successful cartilage repair was also demonstrated when rabbit MSCs were treated with rhTGF-β3-loaded EMLDS ((+ rhTGF-β3 EMLDS in an in vivo model and when rabbit chondrocytes and MSCs were treated in ex vivo models. Therefore, the multilayer ECM membrane could be a useful drug delivery system for cartilage repair.

Terrestrial Gamma-ray Flashes (TGFs) Observed with the Fermi-Gamma-ray Burst Monitor: Temporal and Spectral Properties

Science.gov (United States)

Fishman, G. J.; Briggs, M. S.; Connaughton, W.; Wilson-Hodge, C.; Bhat, P. N.

2010-01-01

The Gamma-ray Burst Monitor (GBM) on the Fermi Gamma-ray Space Telescope Observatory (Fermi) was detecting 2.1 TGFs per week. This rate has increased by a factor of 8 since new flight software was uploaded to the spacecraft in November 2009 in order to increase the sensitivity of GBM to TGFs. Further upgrades to Fermi-GBM to allow observations of weaker TGFs are in progress. The high time resolution (2 s) allows temporal features to be resolved so that some insight may be gained on the origin and transport of the gamma-ray photons through the atmosphere. The absolute time of the TGFs, known to several microseconds, also allows accurate correlations of TGFs with lightning networks and other lightning-related phenomena. The thick bismuth germanate (BGO) scintillation detectors of the GBM system have observed photon energies from TGFs at energies above 40 MeV. New results on the some temporal aspects of TGFs will be presented along with spectral characteristics and properties of several electron-positron TGF events that have been identified.

Research of coal flash hydropyrolysis

Energy Technology Data Exchange (ETDEWEB)

Zhu, Z.; Zhu, H.; Wu, Y.; Tang, L.; Cheng, L.; Xu, Z. [East China University of Science and Technology, Shanghai (China)

2001-02-01

Using x-ray photoelectron spectroscopy (XPS) analyses the organic sufur of seven different Chinese coals and their semi-cokes from flash hydropyrolysis were studied. The results showed that the organic sulfur in coal was alkyal sulfur and thiophene with the peak of XPS located in 163.1-163.5 eV and 164.1-164.5 eV. The relative thiophene content in coal increased with the coal rank. The type of organic sulfur in semi-coke in flash hydropyrolysis was generally thiophene species; its XPS peak also located in 164.1-164.5 eV, and was in accord with its corresponding coal. Total alkyl sulfur and some thiophene sulfur were removed during the flash hydropyrolysis process. The alkyl sulfur had very high activity in hydrogenation reaction. Flash hydropyrolysis was an important new clean-coal technique and had notable desulfurization effect. 13 refs., 2 figs., 4 tabs.

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

Directory of Open Access Journals (Sweden)

Shyam Nyati

2016-12-01

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

Afterglow Observations Shed New Light on the Nature of X-ray Flashes

Energy Technology Data Exchange (ETDEWEB)

Granot, J

2005-02-17

X-ray flashes (XRFs) and X-ray rich gamma-ray bursts (XRGRBs) share many observational characteristics with long duration ({approx}> 2 s) GRBs, but the reason for which the spectral energy distribution of their prompt emission peaks at lower photon energies, E{sub p}, is still a subject of debate. Although many different models have been invoked in order to explain the lower values of E{sub p}, their implications for the afterglow emission were not considered in most cases, mainly because observations of XRF afterglows have become available only recently. Here we examine the predictions of the various XRF models for the afterglow emission, and test them against the observations of XRF 030723 and XRGRB 041006, the events with the best monitored afterglow light curves in their respective class. We show that most existing XRF models are hard to reconcile with the observed afterglow light curves, which are very flat at early times. Such light curves are, however, naturally produced by a roughly uniform jet with relatively sharp edges that is viewed off-axis (i.e. from outside of the jet aperture). This type of model self consistently accommodates both the observed prompt emission and the afterglow light curves of XRGRB 041006 and XRF 030723, implying viewing angles {theta}{sub obs} from the jet axis of ({theta}{sub obs}-{theta}{sub 0}) {approx} 0.15 {theta}{sub 0} and ({theta}{sub obs}-{theta}{sub 0}) {approx} {theta}{sub 0}, respectively, where {theta}{sub 0} {approx} 3{sup o} is the half-opening angle of the jet. This suggests that GRBs, XRGRBs and XRFs are intrinsically similar relativistic jets viewed from different angles. It is then natural to identify GRBs with {gamma}({theta}{sub obs} - {theta}{sub 0}) {approx}< 1, XRGRBs with 1 {approx}< ({theta}{sub obs} - {theta}{sub 0}) {approx}< a few, and XRFs with {gamma}({theta}{sub obs} - {theta}{sub 0}) {approx}> a few, where {gamma} is the Lorentz factor of the outflow near the edge of the jet from which most of the

Reassessing the Role of the Active TGF-β1 as a Biomarker in Systemic Sclerosis: Association of Serum Levels with Clinical Manifestations

Directory of Open Access Journals (Sweden)

Andréa Tavares Dantas

2016-01-01

Full Text Available Objective. To determine active TGF-β1 (aTGF-β1 levels in serum, skin, and peripheral blood mononuclear cell (PBMC culture supernatants and to understand their associations with clinical parameters in systemic sclerosis (SSc patients. Methods. We evaluated serum samples from 56 SSc patients and 24 healthy controls (HC. In 20 SSc patients, we quantified spontaneous or anti-CD3/CD28 stimulated production of aTGF-β1 by PBMC. The aTGF-β1 levels were measured by ELISA. Skin biopsies were obtained from 13 SSc patients and six HC, and TGFB1 expression was analyzed by RT-PCR. Results. TGF-β1 serum levels were significantly higher in SSc patients than in HC (p < 0.0001. Patients with increased TGF-β1 serum levels were more likely to have diffuse subset (p = 0.02, digital ulcers (p = 0.02, lung fibrosis (p < 0.0001, positive antitopoisomerase I (p = 0.03, and higher modified Rodnan score (p = 0.046. Most of our culture supernatant samples had undetectable levels of TGF-β1. No significant difference in TGFB1 expression was observed in the SSc skin compared with HC skin. Conclusion. Raised active TGF-β1 serum levels and their association with clinical manifestations in scleroderma patients suggest that this cytokine could be a marker of fibrotic and vascular involvement in SSc.

Partitioning the LIS/OTD Lightning Climatological Dataset into Separate Ground and Cloud Flash Distributions

Science.gov (United States)

Koshak, W. J.; Solarkiewicz, R. J.

2009-01-01

Presently, it is not well understood how to best model nitrogen oxides (NOx) emissions from lightning because lightning is highly variable. Peak current, channel length, channel altitude, stroke multiplicity, and the number of flashes that occur in a particular region (i.e., flash density) all influence the amount of lightning NOx produced. Moreover, these 5 variables are not the same for ground and cloud flashes; e.g., cloud flashes normally have lower peak currents, higher altitudes, and higher flash densities than ground flashes [see (Koshak, 2009) for additional details]. Because the existing satellite observations of lightning (Fig. 1) from the Lightning Imaging Sensor/Optical Transient Detector (LIS/OTD) do not distinguish between ground and cloud fashes, which produce different amounts of NOx, it is very difficult to accurately account for the regional/global production of lightning NOx. Hence, the ability to partition the LIS/OTD lightning climatology into separate ground and cloud flash distributions would substantially benefit the atmospheric chemistry modeling community. NOx indirectly influences climate because it controls the concentration of ozone and hydroxyl radicals in the atmosphere. The importance of lightning-produced NOx is empasized throughout the scientific literature (see for example, Huntrieser et al. 1998). In fact, lightning is the most important NOx source in the upper troposphere with a global production rate estimated to vary between 2 and 20 Tg (N)yr(sup -1) (Lee et al., 1997), with more recent estimates of about 6 Tg(N)yr(sup -1) (Martin et al., 2007). In order to make accurate predictions, global chemistry/climate models (as well as regional air quality modells) must more accurately account for the effects of lightning NOx. In particular, the NASA Goddard Institute for Space Studies (GISS) Model E (Schmidt et al., 2005) and the GEOS-CHEM global chemical transport model (Bey et al., 2001) would each benefit from a partitioning of the

TGF-β-stimulated aberrant expression of class III β-tubulin via the ERK signaling pathway in cultured retinal pigment epithelial cells

International Nuclear Information System (INIS)

Chung, Eun Jee; Chun, Ji Na; Jung, Sun-Ah; Cho, Jin Won; Lee, Joon H.

2011-01-01

Highlights: ► TGF-β induces aberrant expression of βIII in RPE cells via the ERK pathway. ► TGF-β increases O-GlcNAc modification of βIII in RPE cells. ► Mature RPE cells have the capacity to express a neuron-associated gene by TGF-β. -- Abstract: The class III β-tubulin isotype (β III ) is expressed exclusively by neurons within the normal human retina and is not present in normal retinal pigment epithelial (RPE) cells in situ or in the early phase of primary cultures. However, aberrant expression of class III β-tubulin has been observed in passaged RPE cells and RPE cells with dedifferentiated morphology in pathologic epiretinal membranes from idiopathic macular pucker, proliferative vitreoretinopathy (PVR) and proliferative diabetic retinopathy (PDR). Transforming growth factor-β (TGF-β) has been implicated in dedifferentiation of RPE cells and has a critical role in the development of proliferative vitreoretinal diseases. Here, we investigated the potential effects of TGF-β on the aberrant expression of class III β-tubulin and the intracellular signaling pathway mediating these changes. TGF-β-induced aberrant expression and O-linked-β-N-acetylglucosamine (O-GlcNac) modification of class III β-tubulin in cultured RPE cells as determined using Western blotting, RT-PCR and immunocytochemistry. TGF-β also stimulated phosphorylation of ERK. TGF-β-induced aberrant expression of class III β-tubulin was significantly reduced by pretreatment with U0126, an inhibitor of ERK phosphorylation. Our findings indicate that TGF-β stimulated aberrant expression of class III β-tubulin via activation of the ERK signaling pathway. These data demonstrate that mature RPE cells have the capacity to express a neuron-associated gene in response to TGF-β stimulation and provide useful information towards understanding the pathogenesis of proliferative vitreoretinal diseases.

TGF-{beta}-stimulated aberrant expression of class III {beta}-tubulin via the ERK signaling pathway in cultured retinal pigment epithelial cells

Energy Technology Data Exchange (ETDEWEB)

Chung, Eun Jee [Department of Ophthalmology, National Health Insurance Corporation Ilsan Hospital, Gyeonggi-do (Korea, Republic of); Chun, Ji Na; Jung, Sun-Ah [Konyang University Myunggok Medical Research Institute, Kim' s Eye Hospital, Konyang University College of Medicine, Seoul (Korea, Republic of); Cho, Jin Won [Department of Biology, Yonsei University, 134 Shinchon-dong, Seodaemun-gu, Seoul 120-749 (Korea, Republic of); Lee, Joon H., E-mail: joonhlee@konyang.ac.kr [Konyang University Myunggok Medical Research Institute, Kim' s Eye Hospital, Konyang University College of Medicine, Seoul (Korea, Republic of)

2011-11-18

Highlights: Black-Right-Pointing-Pointer TGF-{beta} induces aberrant expression of {beta}III in RPE cells via the ERK pathway. Black-Right-Pointing-Pointer TGF-{beta} increases O-GlcNAc modification of {beta}III in RPE cells. Black-Right-Pointing-Pointer Mature RPE cells have the capacity to express a neuron-associated gene by TGF-{beta}. -- Abstract: The class III {beta}-tubulin isotype ({beta}{sub III}) is expressed exclusively by neurons within the normal human retina and is not present in normal retinal pigment epithelial (RPE) cells in situ or in the early phase of primary cultures. However, aberrant expression of class III {beta}-tubulin has been observed in passaged RPE cells and RPE cells with dedifferentiated morphology in pathologic epiretinal membranes from idiopathic macular pucker, proliferative vitreoretinopathy (PVR) and proliferative diabetic retinopathy (PDR). Transforming growth factor-{beta} (TGF-{beta}) has been implicated in dedifferentiation of RPE cells and has a critical role in the development of proliferative vitreoretinal diseases. Here, we investigated the potential effects of TGF-{beta} on the aberrant expression of class III {beta}-tubulin and the intracellular signaling pathway mediating these changes. TGF-{beta}-induced aberrant expression and O-linked-{beta}-N-acetylglucosamine (O-GlcNac) modification of class III {beta}-tubulin in cultured RPE cells as determined using Western blotting, RT-PCR and immunocytochemistry. TGF-{beta} also stimulated phosphorylation of ERK. TGF-{beta}-induced aberrant expression of class III {beta}-tubulin was significantly reduced by pretreatment with U0126, an inhibitor of ERK phosphorylation. Our findings indicate that TGF-{beta} stimulated aberrant expression of class III {beta}-tubulin via activation of the ERK signaling pathway. These data demonstrate that mature RPE cells have the capacity to express a neuron-associated gene in response to TGF-{beta} stimulation and provide useful information

IGF-binding proteins mediate TGF-beta 1-induced apoptosis in bovine mammary epithelial BME-UV1 cells.

Science.gov (United States)

Gajewska, Małgorzata; Motyl, Tomasz

2004-10-01

TGF-beta 1 is an antiproliferative and apoptogenic factor for mammary epithelial cells (MEC) acting in an auto/paracrine manner and thus considered an important local regulator of mammary tissue involution. However, the apoptogenic signaling pathway induced by this cytokine in bovine MEC remains obscure. The present study was focused on identification of molecules involved in apoptogenic signaling of transforming growth factor-beta 1 (TGF-beta 1) in the model of bovine mammary epithelial cell line (BME-UV1). Laser scanning cytometry (LSC), Western blot and electrophoretic mobility shift assay (EMSA) were used for analysis of expression and activity of TGF-beta 1-related signaling molecules. The earliest response occurring within 1-2 h after TGF-beta 1 administration was an induction and activation of R-Smads (Smad2 and Smad3) and Co-Smad (Smad4). An evident formation of Smad-DNA complexes began from 2nd hour after MEC exposure to TGF-beta 1. Similarly to Smads, proteins of AP1 complex: phosphorylated c-Jun and JunD appeared to be early reactive molecules; however, an increase in their expression was detected only in cytosolic fraction. In the next step, an increase of IGF binding protein-3 (IGFBP-3) and IGFBP-4 expression was observed from 6th hour followed by a decrease in the activity of protein kinase B (PKB/Akt), which occurred after 24 h of MEC exposure to TGF-beta 1. The decrease in PKB/Akt activity coincided in time with the decline of phosphorylated Bad expression (inactive form). Present study supported additional evidence that stimulation of insulin-like growth factor I (IGF-I) was associated with complete abrogation of TGF-beta 1-induced activation of Bad and Bax and in the consequence protection against apoptosis. In conclusion, apoptotic effect of TGF-beta 1 in bovine MEC is mediated by IGFBPs and occurs through IGF-I sequestration, resulting in inhibition of PKB/Akt-dependent survival pathway.

Modelling and mitigation of Flash Crashes

OpenAIRE

Fry, John; Serbera, Jean-Philippe

2017-01-01

The algorithmic trading revolution has had a dramatic effect upon markets. Trading has become faster, and in some ways more efficient, though potentially at the cost higher volatility and increased uncertainty. Stories of predatory trading and flash crashes constitute a new financial reality. Worryingly, highly capitalised stocks may be particularly vulnerable to flash crashes. Amid fears of high-risk technology failures in the global financial system we develop a model for flash crashes....

The impact of red light running camera flashes on younger and older drivers' attention and oculomotor control.

Science.gov (United States)

Wright, Timothy J; Vitale, Thomas; Boot, Walter R; Charness, Neil

2015-12-01

Recent empirical evidence has suggested that the flashes associated with red light running cameras (RLRCs) distract younger drivers, pulling attention away from the roadway and delaying processing of safety-relevant events. Considering the perceptual and attentional declines that occur with age, older drivers may be especially susceptible to the distracting effects of RLRC flashes, particularly in situations in which the flash is more salient (a bright flash at night compared with the day). The current study examined how age and situational factors potentially influence attention capture by RLRC flashes using covert (cuing effects) and overt (eye movement) indices of capture. We manipulated the salience of the flash by varying its luminance and contrast with respect to the background of the driving scene (either day or night scenes). Results of 2 experiments suggest that simulated RLRC flashes capture observers' attention, but, surprisingly, no age differences in capture were observed. However, an analysis examining early and late eye movements revealed that older adults may have been strategically delaying their eye movements in order to avoid capture. Additionally, older adults took longer to disengage attention following capture, suggesting at least 1 age-related disadvantage in capture situations. Findings have theoretical implications for understanding age differences in attention capture, especially with respect to capture in real-world scenes, and inform future work that should examine how the distracting effects of RLRC flashes influence driver behavior. (c) 2015 APA, all rights reserved).

Electro-optical muzzle flash detection

Science.gov (United States)

Krieg, Jürgen; Eisele, Christian; Seiffer, Dirk

2016-10-01

Localizing a shooter in a complex scenario is a difficult task. Acoustic sensors can be used to detect blast waves. Radar technology permits detection of the projectile. A third method is to detect the muzzle flash using electro-optical devices. Detection of muzzle flash events is possible with focal plane arrays, line and single element detectors. In this paper, we will show that the detection of a muzzle flash works well in the shortwave infrared spectral range. Important for the acceptance of an operational warning system in daily use is a very low false alarm rate. Using data from a detector with a high sampling rate the temporal signature of a potential muzzle flash event can be analyzed and the false alarm rate can be reduced. Another important issue is the realization of an omnidirectional view required on an operational level. It will be shown that a combination of single element detectors and simple optics in an appropriate configuration is a capable solution.

Effects of Irbesartan combined Atorvastatin on serum levels of Cys C, Hcy, TNF-α, ET, TGF-b1 in patients with early diabetic nephropathyn

Directory of Open Access Journals (Sweden)

Abudula.Reziwanguli

2017-10-01

Full Text Available Objective: To observe the effects of Irbesartan combined with Atorvastatin on early diabetic nephropathy patients’ serum Cys C, Hcy, TNF-α, ET and TGF-b1 levels. Methods: A total of 60 early diabetic nephropathy patients were randomly divided into observation group (30 cases and control group (30 cases. Observation group: Irbesartan combined with Atorvastatin; control group: patients were treated only by Irbesartan. Recording and comparing the levels of Cys C, Hcy, TNF-α, ET and TGF-b1 before and after treatment. Results: (1 Before treatment, there was no statistically significant difference in the serum FBG, TG, Scr, BUN levels between the two groups. After treatment, compared with the same group before treatment, the serum TG, Scr, BUN levels of the two groups were significantly lower, and those levels of observation group were significantly better than the control group, the difference between two groups was statistically significant; (2 Before treatment, there was no statistically significant difference in the serum Cys C, Hcy, TNF-α, ET, TGF-b1 levels between the two groups. After treatment, compared with the same group before treatment, the serum Cys C, Hcy, TNF-α, ET, TGF-b1 levels of the two groups were significantly lower, and those levels of observation group were significantly better than the control group, the difference between two groups was statistically significant. Conclusion: Irbesartan combined with Atorvastatin for early diabetic nephropathy patients can reduce the levels of serum Cys C, Hcy, TNF-α, ET, TGF-b1 and be beneficial to protect their nephritic function.

RELATIONSHIP BETWEEN FLASH POINTS OF SOME BINARY ...

African Journals Online (AJOL)

B. S. Chandravanshi

Miscellaneous binary blends containing solvent neutral-150 (SN-150), ... viscosity, the flash point test has always been a standard part of a lubricant's specification. ... between structure and flash points of organic compounds [5-12] and fuels [13, 14]. ... in binary mixtures, the gaps between flash points would be high enough.

PKB/Akt modulates TGF-beta signalling through a direct interaction with Smad3.

Science.gov (United States)

Remy, Ingrid; Montmarquette, Annie; Michnick, Stephen W

2004-04-01

Transforming growth factor beta (TGF-beta) has a major role in cell proliferation, differentiation and apoptosis in many cell types. Integration of the TGF-beta pathway with other signalling cascades that control the same cellular processes may modulate TGF-beta responses. Here we report the discovery of a new functional link between TGF-beta and growth factor signalling pathways, mediated by a physical interaction between the serine-threonine kinase PKB (protein kinase B)/Akt and the transcriptional activator Smad3. Formation of the complex is induced by insulin, but inhibited by TGF-beta stimulation, placing PKB-Smad3 at a point of convergence between these two pathways. PKB inhibits Smad3 by preventing its phosphorylation, binding to Smad4 and nuclear translocation. In contrast, Smad3 does not inhibit PKB. Inhibition of Smad3 by PKB occurs through a kinase-activity-independent mechanism, resulting in a decrease in Smad3-mediated transcription and protection of cells against TGF-beta-induced apoptosis. Consistently, knockdown of the endogenous PKB gene with small-interfering RNA (siRNA) has the opposite effect. Our results suggest a very simple mechanism for the integration of signals arising from growth-factor- and TGF-beta-mediated pathways.

TGF-β1 induces an age-dependent inflammation of nerve ganglia and fibroplasia in the prostate gland stroma of a novel transgenic mouse.

Directory of Open Access Journals (Sweden)

David A Barron

2010-10-01

Full Text Available TGF-β1 is overexpressed in wound repair and in most proliferative disorders including benign prostatic hyperplasia and prostate cancer. The stromal microenvironment at these sites is reactive and typified by altered phenotype, matrix deposition, inflammatory responses, and alterations in nerve density and biology. TGF-β1 is known to modulate several stromal responses; however there are few transgenic models to study its integrated biology. To address the actions of TGF-β1 in prostate disorders, we targeted expression of an epitope tagged and constitutively active TGF-β1 via the enhanced probasin promoter to the murine prostate gland epithelium. Transgenic mice developed age-dependent lesions leading to severe, yet focal attenuation of epithelium, and a discontinuous basal lamina. These changes were associated with elevated fibroplasia and frequency of collagenous micronodules in collapsed acini, along with an induced inflammation in nerve ganglia and small vessels. Elevated recruitment of CD115+ myeloid cells but not mature macrophages was observed in nerve ganglia, also in an age-dependent manner. Similar phenotypic changes were observed using a human prostate epithelium tissue recombination xenograft model, where epithelial cells engineered to overexpress TGF-β1 induced fibrosis and altered matrix deposition concurrent with inflammation in the stromal compartment. Together, these data suggest that elevated TGF-β1 expression induces a fibroplasia stromal response associated with breach of epithelial wall structure and inflammatory involvement of nerve ganglia and vessels. The novel findings of ganglia and vessel inflammation associated with formation of collagenous micronodules in collapsed acini is important as each of these are observed in human prostate carcinoma and may play a role in disease progression.

The peritoneum is both a source and target of TGF-β in women with endometriosis.

Science.gov (United States)

Young, Vicky J; Brown, Jeremy K; Saunders, Philippa T K; Duncan, W Colin; Horne, Andrew W

2014-01-01

Transforming growth factor-β (TGF-β) is believed to play a major role in the aetiology of peritoneal endometriosis. We aimed to determine if the peritoneum is a source of TGF-β and if peritoneal TGF-β expression, reception or target genes are altered in women with endometriosis. Peritoneal fluid, peritoneal bushings and peritoneal biopsies were collected from women with and without endometriosis. TGF-β1, 2 and 3 protein concentrations were measured in the peritoneal fluid. TGF-β1 was measured in mesothelial cell conditioned media. Control peritoneum and peritoneum prone to endometriosis (within Pouch of Douglas) from women without disease (n = 16) and peritoneum distal and adjacent to endometriosis lesions in women with endometriosis (n = 15) and were analysed for TGF-β expression, reception and signalling by immunohistochemistry, qRT-PCR and a TGF-β signalling PCR array. TGF-β1 was increased in the peritoneal fluid of women with endometriosis compared to those without disease (Pperitoneal mesothelial cells secrete TGF-β1 in-vitro. In women with endometriosis, peritoneum from sites adjacent to endometriosis lesions expressed higher levels of TGFB1 mRNA when compared to distal sites (Pendometriosis. In conclusion, the peritoneum, and in particular, the peritoneal mesothelium, is a source of TGF-β1 and this is enhanced around endometriosis lesions. The expression of TGF-β-regulated genes is altered in the peritoneum of women with endometriosis and this may promote an environment favorable to lesion formation.

Meeting report - TGF-β superfamily: signaling in development and disease.

Science.gov (United States)

Zhang, Ying E; Newfeld, Stuart J

2013-11-01

The latest advances on the transforming growth factor β (TGF-β) and bone morphogenetic protein (BMP) signaling pathways were reported at the July 2013 FASEB Summer Research Conference 'The TGF-β Superfamily: Development and Disease'. The meeting was held in Steamboat Springs, Colorado, USA at 6700 feet above sea level in the Rocky Mountains. This was the seventh biannual meeting in the series. In attendance were investigators from a broad range of disciplines with a common interest in the mechanics of TGF-β and BMP signaling pathways, their normal developmental and homeostatic functions, and the diseases associated with pathway misregulation.

XIAP gene expression and function is regulated by autocrine and paracrine TGF-β signaling

Directory of Open Access Journals (Sweden)

Van Themsche Céline

2010-08-01

Full Text Available Abstract Background X-linked inhibitor of apoptosis protein (XIAP is often overexpressed in cancer cells, where it plays a key role in survival and also promotes invasiveness. To date however, the extracellular signals and intracellular pathways regulating its expression and activity remain incompletely understood. We have previously showed that exposure to each of the three TGF-β (transforming growth factor beta isoforms upregulates XIAP protein content in endometrial carcinoma cells in vitro. In the present study, we have investigated the clinical relevance of TGF-β isoforms in endometrial tumours and the mechanisms through which TGF-β isoforms regulate XIAP content in uterine cancer cells. Methods TGF-β isoforms immunoreactivity in clinical samples from endometrial tumours was assessed using immunofluorescence. Two model cancer cell lines (KLE endometrial carcinoma cells and HeLa cervical cancer cells and pharmacological inhibitors were used to investigate the signalling pathways regulating XIAP expression and activity in response to autocrine and paracrine TGF-β in cancer cell. Results We have found immunoreactivity for each TGF-β isoform in clinical samples from endometrial tumours, localizing to both stromal and epithelial/cancer cells. Blockade of autocrine TGF-β signaling in KLE endometrial carcinoma cells and HeLa cervical cancer cells reduced endogenous XIAP mRNA and protein levels. In addition, each TGF-β isoform upregulated XIAP gene expression when given exogenously, in a Smad/NF-κB dependent manner. This resulted in increased polyubiquitination of PTEN (phosphatase and tensin homolog on chromosome ten, a newly identified substrate for XIAP E3 ligase activity, and in a XIAP-dependent decrease of PTEN protein levels. Although each TGF-β isoform decreased PTEN content in a XIAP- and a Smad-dependent manner, decrease of PTEN levels in response to only one isoform, TGF-β3, was blocked by PI3-K inhibitor LY294002. Conclusions

A cluster of coregulated genes determines TGF-beta-induced regulatory T-cell (Treg) dysfunction in NOD mice.

Science.gov (United States)

D'Alise, Anna Morena; Ergun, Ayla; Hill, Jonathan A; Mathis, Diane; Benoist, Christophe

2011-05-24

Foxp3(+) regulatory T cells (Tregs) originate in the thymus, but the Treg phenotype can also be induced in peripheral lymphoid organs or in vitro by stimulation of conventional CD4(+) T cells with IL-2 and TGF-β. There have been divergent reports on the suppressive capacity of these TGF-Treg cells. We find that TGF-Tregs derived from diabetes-prone NOD mice, although expressing normal Foxp3 levels, are uniquely defective in suppressive activity, whereas TGF-Tregs from control strains (B6g7) or ex vivo Tregs from NOD mice all function normally. Most Treg-typical transcripts were shared by NOD or B6g7 TGF-Tregs, except for a small group of differentially expressed genes, including genes relevant for suppressive activity (Lrrc32, Ctla4, and Cd73). Many of these transcripts form a coregulated cluster in a broader analysis of T-cell differentiation. The defect does not map to idd3 or idd5 regions. Whereas Treg cells from NOD mice are normal in spleen and lymph nodes, the NOD defect is observed in locations that have been tied to pathogenesis of diabetes (small intestine lamina propria and pancreatic lymph node). Thus, a genetic defect uniquely affects a specific Treg subpopulation in NOD mice, in a manner consistent with a role in determining diabetes susceptibility.

Role of transforming growth factor-beta (TGF) beta in the physiopathology of rheumatoid arthritis.

Science.gov (United States)

Gonzalo-Gil, Elena; Galindo-Izquierdo, María

2014-01-01

Transforming growth factor-beta (TGF-β) is a cytokine with pleiotropic functions in hematopoiesis, angiogenesis, cell proliferation, differentiation, migration and apoptosis. Although its role in rheumatoid arthritis is not well defined, TGF-β activation leads to functional immunomodulatory effects according to environmental conditions. The function of TGF-β in the development of arthritis in murine models has been extensively studied with controversial results. Recent findings point to a non-relevant role for TGF-β in a mice model of collagen-induced arthritis. The study of TGF-β on T-cell responses has shown controversial results as an inhibitor or promoter of the inflammatory response. This paper presents a review of the role of TGF-β in animal models of arthritis. Copyright © 2013 Elsevier España, S.L. All rights reserved.

Flash x-ray

International Nuclear Information System (INIS)

Johnson, Q.; Pellinen, D.

1976-01-01

The complementary techniques of flash x-ray radiography (FXR) and flash x-ray diffraction (FXD) provide access to a unique domain in nondestructive materials testing. FXR is useful in studies of macroscopic properties during extremely short time intervals, and FXD, the newer technique, is used in studies of microscopic properties. Although these techniques are similar in many respects, there are some substantial differences. FXD generally requires low-voltage, line-radiation sources and extremely accurate timing; FXR is usually less demanding. Phenomena which can be profitably studied by FXR often can also be studied by FXD to permit a complete materials characterization

Flash CS5.5 The Missing Manual

CERN Document Server

Grover, Chris

2011-01-01

You can build everything from simple animations to full-fledged iOS and Android apps with Flash CS5.5, but learning this complex program can be difficult-unless you have this fully updated, bestselling guide. Learn how to create gorgeous Flash effects even if you have no programming experience. With Flash CS5.5: The Missing Manual, you'll move from the basics to power-user tools with ease. Learn animation basics. Discover how to turn simple ideas into stunning animations.Master Flash's tools. Learn the animation and effects tools with clear explanations and hands-on examples.Use 3D effects. R

Aberrant Expression of TNF-α and TGF-β1 mRNA in Spontaneous Abortion

Institute of Scientific and Technical Information of China (English)

Ji-fen HU; Hong-chu BAO; Feng-chuan ZHU; Cai-ling YOU

2004-01-01

Objective To investigate the aberrant expressions of TNF-α and TGF-β1 in peripheral blood mononuclear cells (PBMCs) and placental tissues in patients with early spontaneous abortionMethods Using the technique of semi-quantitative reverse transcript-polymerase chain reaction (RT-PCR), TNF-α mRNA and TGF-β1 mRNA in PBMCs were measured in spontaneous abortion group (30 cases), normal pregnancy group (25 cases) and nonpregnant group (25 cases). The expressive intension of TNF-α protein and TGF-β1 protein in placental tissues was also identified by immunohistochemistry.Results Both levels of TNF-α mRNA and TGF-β1 mRNA expressed in PBMCs were significantly different between the three groups respectively (P＜0. 05). Levels of TNF-α in syncytiotrophoblastic and cytotrophoblastic cells of the two aborted groups were substantially higher than those of the non-pregnant group (P＜0. 01), but the levels of TGF-β1 in syncytiotrophoblastic cells of the two aborted groups were markedly lower than those of the non-pregnant group (P＜0. 01).Conclusion There is potential relation between TGF-β1 at the fetomaternal interface and spontaneous abortion. TGF-β1 may contribute to the maintenance of pregnancy,and low-level expression of TGF-β1 may be associated with pregnancy failure.

The peritoneum is both a source and target of TGF-β in women with endometriosis.

Directory of Open Access Journals (Sweden)

Vicky J Young

Full Text Available Transforming growth factor-β (TGF-β is believed to play a major role in the aetiology of peritoneal endometriosis. We aimed to determine if the peritoneum is a source of TGF-β and if peritoneal TGF-β expression, reception or target genes are altered in women with endometriosis. Peritoneal fluid, peritoneal bushings and peritoneal biopsies were collected from women with and without endometriosis. TGF-β1, 2 and 3 protein concentrations were measured in the peritoneal fluid. TGF-β1 was measured in mesothelial cell conditioned media. Control peritoneum and peritoneum prone to endometriosis (within Pouch of Douglas from women without disease (n = 16 and peritoneum distal and adjacent to endometriosis lesions in women with endometriosis (n = 15 and were analysed for TGF-β expression, reception and signalling by immunohistochemistry, qRT-PCR and a TGF-β signalling PCR array. TGF-β1 was increased in the peritoneal fluid of women with endometriosis compared to those without disease (P<0.05 and peritoneal mesothelial cells secrete TGF-β1 in-vitro. In women with endometriosis, peritoneum from sites adjacent to endometriosis lesions expressed higher levels of TGFB1 mRNA when compared to distal sites (P<0.05. The TGF-β-stimulated Smad 2/3 signalling pathway was active in the peritoneum and there were significant increases (P<0.05 in expression of genes associated with tumorigenesis (MAPK8, CDC6, epithelial-mesenchymal transition (NOTCH1, angiogenesis (ID1, ID3 and neurogenesis (CREB1 in the peritoneum of women with endometriosis. In conclusion, the peritoneum, and in particular, the peritoneal mesothelium, is a source of TGF-β1 and this is enhanced around endometriosis lesions. The expression of TGF-β-regulated genes is altered in the peritoneum of women with endometriosis and this may promote an environment favorable to lesion formation.

Mechanisms of Intestinal Serotonin Transporter (SERT Upregulation by TGF-β1 Induced Non-Smad Pathways.

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Saad Nazir

Full Text Available TGF-β1 is an important multifunctional cytokine with numerous protective effects on intestinal mucosa. The influence of TGF-β1 on serotonin transporter (SERT activity, the critical mechanism regulating the extracellular availability of serotonin (5-HT, is not known. Current studies were designed to examine acute effects of TGF-β1 on SERT. Model human intestinal Caco-2 cells grown as monolayer's or as cysts in 3D culture and ex vivo mouse model were utilized. Treatment of Caco-2 cells with TGF-β1 (10 ng/ml, 60 min stimulated SERT activity (~2 fold, P<0.005. This stimulation of SERT function was dependent upon activation of TGF-β1 receptor (TGFRI as SB-431542, a specific TGF-βRI inhibitor blocked the SERT stimulation. SERT activation in response to TGF-β1 was attenuated by inhibition of PI3K and occurred via enhanced recruitment of SERT-GFP to apical surface in a PI3K dependent manner. The exocytosis inhibitor brefeldin A (2.5 μM attenuated the TGF-β1-mediated increase in SERT function. TGF-β1 increased the association of SERT with the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE syntaxin 3 (STX3 and promoted exocytosis of SERT. Caco-2 cells grown as cysts in 3D culture recapitulated the effects of TGF-β1 showing increased luminal staining of SERT. Ussing chamber studies revealed increase in 3H-5-HT uptake in mouse ileum treated ex vivo with TGF-β1 (10 ng/ml, 1h. These data demonstrate a novel mechanism rapidly regulating intestinal SERT via PI3K and STX3. Since decreased SERT is implicated in various gastro-intestinal disorders e.g IBD, IBS and diarrhea, understanding mechanisms stimulating SERT function by TGF-β1 offers a novel therapeutic strategy to treat GI disorders.

Hot Flashes amd Night Sweats (PDQ)

Science.gov (United States)

... Professionals Questions to Ask about Your Treatment Research Hot Flashes and Night Sweats (PDQ®)–Patient Version Overview ... quality of life in many patients with cancer. Hot flashes and night sweats may be side effects ...

"Know What to Do If You Encounter a Flash Flood": Mental Models Analysis for Improving Flash Flood Risk Communication and Public Decision Making.

Science.gov (United States)

Lazrus, Heather; Morss, Rebecca E; Demuth, Julie L; Lazo, Jeffrey K; Bostrom, Ann

2016-02-01

Understanding how people view flash flood risks can help improve risk communication, ultimately improving outcomes. This article analyzes data from 26 mental models interviews about flash floods with members of the public in Boulder, Colorado, to understand their perspectives on flash flood risks and mitigation. The analysis includes a comparison between public and professional perspectives by referencing a companion mental models study of Boulder-area professionals. A mental models approach can help to diagnose what people already know about flash flood risks and responses, as well as any critical gaps in their knowledge that might be addressed through improved risk communication. A few public interviewees mentioned most of the key concepts discussed by professionals as important for flash flood warning decision making. However, most interviewees exhibited some incomplete understandings and misconceptions about aspects of flash flood development and exposure, effects, or mitigation that may lead to ineffective warning decisions when a flash flood threatens. These include important misunderstandings about the rapid evolution of flash floods, the speed of water in flash floods, the locations and times that pose the greatest flash flood risk in Boulder, the value of situational awareness and environmental cues, and the most appropriate responses when a flash flood threatens. The findings point to recommendations for ways to improve risk communication, over the long term and when an event threatens, to help people quickly recognize and understand threats, obtain needed information, and make informed decisions in complex, rapidly evolving extreme weather events such as flash floods. © 2015 Society for Risk Analysis.

Laser-flash calorimetry

International Nuclear Information System (INIS)

Takahashi, Y.; Nakamura, J.-I.

1982-01-01

The heat capacity of vanadium has been measured by laser-flash calorimetry in the temperature region from 80 to 1000 K. The results are compared with available low- and high-temperature heat capacities, and revised thermodynamic values of vanadium are given. No heat-capacity anomaly has been found in the pure vanadium sample over the temperature range investigated, while a small heat-capacity discontinuity, less than 1.2 J.K -1 .mol -1 , has been observed at 220 to 230 K on the same sample but electropolished before measurement. This anomaly disappeared after annealing at 1000 K in vacuo for 1 h and is attributable to the introduction of a small amount of hydrogen during electropolishing. (author)

TGF-β in pancreatic cancer initiation and progression: two sides of the same coin.

Science.gov (United States)

Shen, Wei; Tao, Guo-Qing; Zhang, Yu; Cai, Bing; Sun, Jian; Tian, Zhi-Qiang

2017-01-01

Pancreatic cancer is highly lethal malignant tumor with characterised rapid progression, invasiveness and resistance to radiochemotherapy. Transforming growth factor-β (TGF-β) signaling plays a dual role in both pro-tumorigenic and tumor suppressive of pancreatic cancer, depending on tumor stage and microenvironment. TGF-β signaling components alteration are common in pancreatic cancer, and its leading role in tumor formation and metastases has received increased attention. Many therapies have investigated to target TGF-β signaling in the preclinical and clinical setting. In this review, we highlight the dual roles of TGF-β and touch upon the perspectives on therapeutic target of TGF-β signaling in pancreatic cancer.

TGF-β1 regulation of estrogen production in mature rat Leydig cells.

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Man-Li Liu

Full Text Available BACKGROUND: Besides androgens, estrogens produced in Leydig cells are also crucial for mammalian germ cell differentiation. Transforming growth factor-β1 (TGF-β1 is now known to have multiple effects on regulation of Leydig cell function. The objective of the present study is to determine whether TGF-β1 regulates estradiol (E2 synthesis in adult rat Leydig cells and then to assess the impact of TGF-β1 on Cx43-based gap junctional intercellular communication (GJIC between Leydig cells. METHODOLOGY/PRINCIPAL FINDINGS: Primary cultured Leydig cells were incubated in the presence of recombinant TGF-β1 and the production of E2 as well as testosterone (T were measured by RIA. The activity of P450arom was addressed by the tritiated water release assay and the expression of Cyp19 gene was evaluated by Western blotting and real time RT-PCR. The expression of Cx43 and GJIC were investigated with immunofluorescence and fluorescence recovery after photo-bleaching (FRAP, respectively. Results from this study show that TGF-β1 down-regulates the level of E2 secretion and the activity of P450arom in a dose-dependent manner in adult Leydig cells. In addition, the expression of Cx43 and GJIC was closely related to the regulation of E2 and TGF-β1, and E2 treatment in turn restored the inhibition of TGF-β1 on GJIC. CONCLUSIONS: Our results indicate, for the first time in adult rat Leydig cells, that TGF-β1 suppresses P450arom activity, as well as the expression of the Cyp19 gene, and that depression of E2 secretion leads to down-regulation of Cx43-based GJIC between Leydig cells.

Evaluation of Flash Bainite in 4130 Steel

Science.gov (United States)

2011-07-01

Technical Report ARWSB-TR-11011 Evaluation of Flash Bainite in 4130 Steel G. Vigilante M. Hespos S. Bartolucci...4. TITLE AND SUBTITLE Evaluation of Flash Bainite in 4130 Steel 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT...need to be addressed, the Flash Bainite processing of 4130 steel demonstrates promise for applications needing a combination of high strength with

Flash-Aware Page Replacement Algorithm

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Guangxia Xu

2014-01-01

Full Text Available Due to the limited main memory resource of consumer electronics equipped with NAND flash memory as storage device, an efficient page replacement algorithm called FAPRA is proposed for NAND flash memory in the light of its inherent characteristics. FAPRA introduces an efficient victim page selection scheme taking into account the benefit-to-cost ratio for evicting each victim page candidate and the combined recency and frequency value, as well as the erase count of the block to which each page belongs. Since the dirty victim page often contains clean data that exist in both the main memory and the NAND flash memory based storage device, FAPRA only writes the dirty data within the victim page back to the NAND flash memory based storage device in order to reduce the redundant write operations. We conduct a series of trace-driven simulations and experimental results show that our proposed FAPRA algorithm outperforms the state-of-the-art algorithms in terms of page hit ratio, the number of write operations, runtime, and the degree of wear leveling.

Turbulent spots and scalar flashes in pipe transition

Science.gov (United States)

Adrian, Ronald; Wu, Xiaohua; Moin, Parviz

2017-11-01

Recent study (Wu et al., PNAS, 1509451112, 2015) demonstrated the feasibility and accuracy of direct computation of the Osborne Reynolds' pipe transition experiment without the unphysical axially periodic boundary condition. Here we use this approach to address three questions: (1) What are the dynamics of turbulent spot generation in pipe transition? (2) How is the succession of scalar flashes, as observed and sketched by Osborne Reynolds, created? (3) What happens to the succession of flashes further downstream? In this study, the inlet disturbance is of radial-mode type imposed through a narrow, three-degree numerical wedge; and the simulation Reynolds number is 6500. Numerical dye is introduced at the inlet plane locally very close to the pipe axis, similar to the needle injection by O. Reynolds. Inception of infant turbulent spots occurs when normal, forward inclined hairpin packets form near the walls from the debris of the inlet perturbations. However, the young and mature turbulent spots consist almost exclusively of reverse, backward leaning hairpin vortices. Scalar flashes appear successively downstream and persist well into the fully-developed turbulent region. Their creation mechanism is addressed. RJA gratefully acknowledges support of the National Science Foundation with NSF Award CBET-0933848.

Serum TGF-beta2 and TGF-beta3 are increased and positively correlated to pain, functionality, and radiographic staging in osteoarthritis.

Science.gov (United States)

Kapetanakis, Stilianos; Drygiannakis, Ioannis; Kazakos, Kostantinos; Papanas, Nikolaos; Kolios, George; Kouroumalis, Elias; Verettas, Dionysios-Alexandros

2010-08-11

The goal of this study was to verify or reject the hypothesis that systematic differences exist in various profibrotic or antifibrotic factors between osteoarthritic patients and controls, as well as between different stages of osteoarthritis. The study group comprised 63 patients with knee osteoarthritis and 18 controls. Transforming growth factor-beta (TGF-beta)1, -2, -3; tissue inhibitor of metalloproteinase (TIMP)-1 protein levels; and gelatinolytic activity of matrix metalloproteinase (MMP)-1, -2, -3, -9 activities were measured by enzyme-linked immunosorbent assay and gelatin zymography, respectively. Visual analog scale scores, Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores, Lequesne clinical osteoarthritis scales, and Kellgren-Lawrence radiographic grading were recorded for each patient.Transforming growth factor-beta2 and -3 (in contrast to TGF-beta1 and TIMP-1) serum protein levels were significantly higher in osteoarthritic patients compared to controls (210%+/-14% [P<.001] and 232%+/-7% [P<10(-7)], respectively). Additionally, TGF-beta2 and -3 were strongly positively correlated to Kellgren-Lawrence radiographic grading of the disease (P<10(-5) and P<10(-7), respectively). Moreover, TGF-beta2 correlated positively with the WOMAC scale (P=.007). However, TIMP-1 decreased as osteoarthritis progressed clinically, but remained irrelevant to radiographic staging. Furthermore, activities of MMP-2 and -9, but not MMP-1+/-3, were lower in patients with osteoarthritis. Copyright 2010, SLACK Incorporated.

Principles of arc flash protection

Energy Technology Data Exchange (ETDEWEB)

Hirschmann, R. B.

2003-04-01

Recent developments in NFPA 70E, the electrical safety standards in the United States and Canada, designed to provide for a safe industrial work environment, are discussed. The emphasis in this instance is on arc explosions. Development of an arc flash protective program is discussed under various major components of an electrical safety program. These are: appropriate qualifications and training for workers, safe work practices, appropriate hazard assessment practices for any task exceeding 50V where there is the potential of an arc flash accident, flash protection equipment commensurate with the hazard associated with the task to be performed, layering in protective clothing over all body surfaces, and strict adherence to rules regarding use of safety garments and equipment.

DHEA-induced ovarian hyperfibrosis is mediated by TGF-β signaling pathway.

Science.gov (United States)

Wang, Daojuan; Wang, Wenqing; Liang, Qiao; He, Xuan; Xia, Yanjie; Shen, Shanmei; Wang, Hongwei; Gao, Qian; Wang, Yong

2018-01-10

The polycystic ovary syndrome (PCOS) is a common metabolic and endocrine disorder with pathological mechanisms remain unclear. The following study investigates the ovarian hyperfibrosis forming via transforming growth factor-β (TGF-β) signaling pathway in Dehydroepiandrosterone (DHEA)- induced polycystic ovary syndrome (PCOS) rat model. We furthermore explored whether TGF-βRI inhibitor (SB431542) decreases ovarian fibrosis by counterbalancing the expression of fibrotic biomarkers. Thirty female Sprague-Dawley rats were randomly divided into Blank group (n = 6), Oil group (n = 6), and Oil + DHEA-induced model group (n = 6 + 12). The model groups were established by subcutaneous injection of DHEA for 35 consecutive days. The 12 successful model rats were additionally divided in vehicle group (n = 6) and SB431542-treated group (n = 6). Vehicle group and SB431542-treated group, served as administration group and were intraperitoneally injected with DMSO and SB431542 for additional 14 consecutive days. Ovarian morphology, fibrin and collagen localization and expression in ovaries were detected using H&E staining, immunohistochemistry and Sirius red staining. The ovarian protein and RNA were examined using Western blot and RT-PCR. In DHEA-induced ovary in rat, fibrin and collagen had significantly higher levels, while the main fibrosis markers (TGF-β, CTGF, fibronectin, a-SMA) were obviously upregulated. SB431542 significantly reduced the expression of pro-fibrotic molecules (TGF-β, Smad3, Smad2, a-SMA) and increased anti-fibrotic factor MMP2. TGF-βRI inhibitor (SB431542) inhibits the downstream signaling molecules of TGF-β and upregulates MMP2, which in turn prevent collagen deposition. Moreover, ovarian hyperfibrosis in DHEA-induced PCOS rat model could be improved by TGF-βRI inhibitor (SB431542) restraining the transcription of accelerating fibrosis genes and modulating EMT mediator.

The Peritoneum Is Both a Source and Target of TGF-β in Women with Endometriosis

Science.gov (United States)

Young, Vicky J.; Brown, Jeremy K.; Saunders, Philippa T. K.; Duncan, W. Colin; Horne, Andrew W.

2014-01-01

Transforming growth factor-β (TGF-β) is believed to play a major role in the aetiology of peritoneal endometriosis. We aimed to determine if the peritoneum is a source of TGF-β and if peritoneal TGF-β expression, reception or target genes are altered in women with endometriosis. Peritoneal fluid, peritoneal bushings and peritoneal biopsies were collected from women with and without endometriosis. TGF-β1, 2 and 3 protein concentrations were measured in the peritoneal fluid. TGF-β1 was measured in mesothelial cell conditioned media. Control peritoneum and peritoneum prone to endometriosis (within Pouch of Douglas) from women without disease (n = 16) and peritoneum distal and adjacent to endometriosis lesions in women with endometriosis (n = 15) and were analysed for TGF-β expression, reception and signalling by immunohistochemistry, qRT-PCR and a TGF-β signalling PCR array. TGF-β1 was increased in the peritoneal fluid of women with endometriosis compared to those without disease (Pendometriosis, peritoneum from sites adjacent to endometriosis lesions expressed higher levels of TGFB1 mRNA when compared to distal sites (Pendometriosis. In conclusion, the peritoneum, and in particular, the peritoneal mesothelium, is a source of TGF-β1 and this is enhanced around endometriosis lesions. The expression of TGF-β-regulated genes is altered in the peritoneum of women with endometriosis and this may promote an environment favorable to lesion formation. PMID:25207642

The Effect of 5 FU on the Expression of Transforming Growth Factor Beta-1 (Tgf-1 in Cultured Tendon Cells

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Zeynep Karacor Altuntas

2014-10-01

Full Text Available This study investigated the effect of the treatment with 1 min exposures to 5-fluorouracil (5-FU  on the expression of TGF-beta 1 in cultured tendon cells. Fibroblasts cultured from the flexor tendons of dog paws were treated with 3 different doses of 5-FU ( control, 5-15-25 mgr /ml for 1 minute.  After 5-FU exposure  the expression of TGF –beta 1 were tested by real time Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR at 3rd and 7th days. There were no statistically significant differences in the expression levels of the TGF-b1 gene between the control group and all other groups on day 3 and 7 (p>0.05.However, when the percentage changes in the TGF-BETA1 gene expression on days 3–7 were compared, there were statistically significant differences and this was maximally observed with 89% +12 (p<0.05 in the group treated with 25-mg/ml 5-FU.  We conclude that 1min. 5-FU application may be  sufficient to prevent adhesions in tendon healing by limiting the expression of TGF-BETA1. 

Immunohistochemical Expression of TGF-Β1, SMAD4, SMAD7, TGFβRII and CD68-Positive TAM Densities in Papillary Thyroid Cancer

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Koni Ivanova

2018-03-01

Full Text Available BACKGROUND: Papillary thyroid carcinoma (PTC accounts for 80% of the thyroid malignancies that are characterised by slow growth and an excellent prognosis. Over-expression of SMAD4 protein restores TGF-β signalling, determines a strong increase in anti-proliferative effect and reduces invasive potential of tumour cells expressing it. AIM: The study aimed to analyse the immunohistochemical expression of TGF-β1 and its downstream phosphorylated SMAD4, element and of the inhibitory SMAD7 PTC variants and their association with the localisation of TAMs within the tumour microenvironment. METHODS: For this retrospective study we investigated 69 patients immunohistochemistry with antibodies against TGF-β, TGF – β-RII, SMAD4, SMAD7, CD68+ macrophages. RESULTS: Patients with low infiltration with CD68+ cells in tumour stroma has significantly shorter survival (median of 129.267 months compared to those with high CD68+ cells infiltration (p = 0.034. From the analysis of CD68+ cells in tumour border and tumour stroma correlated with expression of TGF-β1 / SMAD proteins, we observed that the positive expression of TGF-β1 in tumour cytoplasm, significantly correlated with increased number of CD68+ cells in tumour border (X2 = 5,945; р = 0.015. CONCLUSION: TGF-β enhances motility and stimulates recruitment of monocytes, macrophages and other immune cells while directly inhibiting their anti-tumour effector functions.

Analysis of interleukin (IL)-1 beta and transforming growth factor (TGF)-beta-induced signal transduction pathways in IL-2 and TGF-beta secretion and proliferation in the thymoma cell line EL4.NOB-1.

Science.gov (United States)

Siese, A; Jaros, P P; Willig, A

1999-02-01

In the present study we investigated the interleukin (IL)-1beta and transforming growth factor-beta1 (TGF-beta1)-mediated proliferation, and production of IL-2 and TGF-beta, in the murine T-cell line, EL4.NOB-1. This cell line is resistant to TGF-beta concerning growth arrest but not autoinduction or suppression of IL-1-induced IL-2 production. When cocultured with IL-1beta, TGF-beta showed growth-promoting activity that could be antagonized by adding the phosphatidyl choline-dependent phospholipase C (PC-PLC) inhibitor, D609. Using specific enzyme inhibitors of protein kinases (PK) C and A, mitogen-activated protein kinase (MAPK), phospholipase A2 (PLA2), phosphatidylinositol-dependent (PI)-PLC and PC-PLC, we showed that IL-1beta-induced IL-2 synthesis was dependent on all investigated kinases and phospholipases, except PC-PLC. TGF-beta1 was able to inhibit IL-2 synthesis by the activation of PKA and MAPK. The same kinases are involved in TGF-beta autoinduction that is accompanied by a secretion of the active but not the latent growth factor and is antagonized by IL-1beta. Addition of the PI-PLC inhibitor, ET 18OCH3, or the PLA2 inhibitor (quinacrine) alone, resulted in secretion of latent TGF-beta and, in the case of ET 18OCH3, active TGF-beta. These data implicate a role for PI-PLC and PLA2 in the control of latency and secretion. Analysis of specific tyrosine activity and c-Fos expression showed synergistic but no antagonistic effects. These events are therefore not involved in IL- and TGF-beta-regulated IL-2 and TGF-beta production, but might participate in IL-1/TGF-beta-induced growth promotion.

Registration of X-rays at 2500 m altitude in association with lightning flashes and thunderstorms

OpenAIRE

Montañá Puig, Juan; Fabró Tàpia, Ferran; Van der Velde, Oscar Arnoud; Romero Durán, David; Solà de Las Fuentes, Gloria; Hermoso Costa, Juan Ramón; Soula, Serge; Williams, Earle; Pineda Ruegg, Nicolau

2014-01-01

Electric fields and high-energy radiation of natural lightning measured at close range from a mountaintop tower are discussed. In none of the 12 negative cloud-to-ground upward flashes were X-rays observed. Also no energetic radiation was found in one negative upward leader at close range (20¿m). In the first of two consecutive negative cloud-to-ground flashes, X-rays were detected during the last ~1.75¿ms of the leader. During the time of energetic radiation in the flash an intense burst of ...

Essential role of TGF-beta/Smad pathway on statin dependent vascular smooth muscle cell regulation.

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Juan Rodríguez-Vita

Full Text Available BACKGROUND: The 3-hydroxy-3-methylglutaryl CoA reductase inhibitors (also called statins exert proven beneficial effects on cardiovascular diseases. Recent data suggest a protective role for Transforming Growth Factor-beta (TGF-beta in atherosclerosis by regulating the balance between inflammation and extracellular matrix accumulation. However, there are no studies about the effect of statins on TGF-beta/Smad pathway in atherosclerosis and vascular cells. METHODOLOGY: In cultured vascular smooth muscle cells (VSMCs statins enhanced Smad pathway activation caused by TGF-beta. In addition, statins upregulated TGF-beta receptor type II (TRII, and increased TGF-beta synthesis and TGF-beta/Smad-dependent actions. In this sense, statins, through Smad activation, render VSMCs more susceptible to TGF-beta induced apoptosis and increased TGF-beta-mediated ECM production. It is well documented that high doses of statins induce apoptosis in cultured VSMC in the presence of serum; however the precise mechanism of this effect remains to be elucidated. We have found that statins-induced apoptosis was mediated by TGF-beta/Smad pathway. Finally, we have described that RhoA inhibition is a common intracellular mechanisms involved in statins effects. The in vivo relevance of these findings was assessed in an experimental model of atherosclerosis in apolipoprotein E deficient mice: Treatment with Atorvastatin increased Smad3 phosphorylation and TRII overexpression, associated to elevated ECM deposition in the VSMCs within atheroma plaques, while apoptosis was not detected. CONCLUSIONS: Statins enhance TGF-beta/Smad pathway, regulating ligand levels, receptor, main signaling pathway and cellular responses of VSMC, including apoptosis and ECM accumulation. Our findings show that TGF-beta/Smad pathway is essential for statins-dependent actions in VSMCs.

Geographical distribution of hot flash frequencies: considering climatic influences.

Science.gov (United States)

Sievert, Lynnette Leidy; Flanagan, Erin K

2005-10-01

Laboratory studies suggest that hot flashes are triggered by small elevations in core body temperature acting within a reduced thermoneutral zone, i.e., the temperature range in which a woman neither shivers nor sweats. In the present study, it was hypothesized that women in different populations develop climate-specific thermoneutral zones, and ultimately, population-specific frequencies of hot flashes at menopause. Correlations were predicted between hot flash frequencies and latitude, elevation, and annual temperatures. Data on hot flash frequencies were drawn from 54 studies. Pearson correlation analyses and simple linear regressions were applied, first using all studies, and second using a subset of studies that included participants only to age 60 (n = 36). Regressions were repeated with all studies, controlling for method of hot flash assessment. When analyses were restricted to studies that included women up to age 60, average temperature of the coldest month was a significant predictor of hot flash frequency (P hottest and coldest temperatures was also a significant predictor (P coldest month, difference between hottest and coldest temperatures, and mean annual temperature were significant predictors of hot flash frequency. Women reported fewer hot flashes in warmer temperatures, and more hot flashes with increasing seasonality. These results suggest that acclimatization to coldest temperatures or sensitivity to seasonality may explain part of the population variation in hot flash frequency.

Organic flash cycles for efficient power production

Science.gov (United States)

Ho, Tony; Mao, Samuel S.; Greif, Ralph

2016-03-15

This disclosure provides systems, methods, and apparatus related to an Organic Flash Cycle (OFC). In one aspect, a modified OFC system includes a pump, a heat exchanger, a flash evaporator, a high pressure turbine, a throttling valve, a mixer, a low pressure turbine, and a condenser. The heat exchanger is coupled to an outlet of the pump. The flash evaporator is coupled to an outlet of the heat exchanger. The high pressure turbine is coupled to a vapor outlet of the flash evaporator. The throttling valve is coupled to a liquid outlet of the flash evaporator. The mixer is coupled to an outlet of the throttling valve and to an outlet of the high pressure turbine. The low pressure turbine is coupled to an outlet of the mixer. The condenser is coupled to an outlet of the low pressure turbine and to an inlet of the pump.

Sorafenib suppresses TGF-β responses by inducing caveolae/lipid raft-mediated internalization/degradation of cell-surface type II TGF-β receptors: Implications in development of effective adjunctive therapy for hepatocellular carcinoma.

Science.gov (United States)

Chung, Chih-Ling; Wang, Shih-Wei; Sun, Wei-Chih; Shu, Chih-Wen; Kao, Yu-Chen; Shiao, Meng-Shin; Chen, Chun-Lin

2018-04-18

Sorafenib is the only FDA approved drug for the treatment of advanced hepatocellular carcinoma (HCC) and other malignancies. Studies indicate that TGF-β signalling is associated with tumour progression in HCC. Autocrine and paracrine TGF-β promotes tumour growth and malignancy by inducing epithelial-mesenchymal transition (EMT). Sorafenib is believed to antagonize tumour progression by inhibiting TGF-β-induced EMT. It improves survival of patients but HCC later develops resistance and relapses. The underlying mechanism of resistance is unknown. Understanding of the molecular mechanism of sorafenib inhibition of TGF-β-induced signalling or responses in HCC may lead to development of adjunctive effective therapy for HCC. In this study, we demonstrate that sorafenib suppresses TGF-β responsiveness in hepatoma cells, hepatocytes, and animal liver, mainly by downregulating cell-surface type II TGF-β receptors (TβRII) localized in caveolae/lipid rafts and non-lipid raft microdomains via caveolae/lipid rafts-mediated internalization and degradation. Furthermore, sorafenib-induced downregulation and degradation of cell-surface TβRII is prevented by simultaneous treatment with a caveolae disruptor or lysosomal inhibitors. On the other hand, sorafenib only downregulates cell-surface TβRII localized in caveolae/lipid rafts but not localized in non-lipid raft microdomains in hepatic stellate cells. These results suggest that sorafenib inhibits TGF-β signalling mainly by inducing caveolae/lipid raft-mediated internalization and degradation of cell-surface TβR-II in target cells. They may also imply that treatment with agents which promote formation of caveolae/lipid rafts, TGF-β receptor kinase inhibitors (e.g., LY2157299) or TGF-β peptide antagonists (by liver-targeting delivery) may be considered as effective adjunct therapy with sorafenib for HCC. Copyright © 2018 Elsevier Inc. All rights reserved.

Construction and performance of large flash chambers

International Nuclear Information System (INIS)

Taylor, F.E.; Bogert, D.; Fisk, R.; Stutte, L.; Walker, J.K.; Wolfson, J.; Abolins, M.; Ernwein, J.; Owen, D.; Lyons, T.

1979-01-01

The construction and performance of 12' x 12' flash chambers used in a 340 ton neutrino detector under construction at Fermilab is described. The flash chambers supply digital information with a spatial resolution of 0.2'', and are used to finely sample the shower development of the reaction products of neutrino interactions. The flash chambers are easy and inexpensive to build and are electronically read out

Non Volatile Flash Memory Radiation Tests

Science.gov (United States)

Irom, Farokh; Nguyen, Duc N.; Allen, Greg

2012-01-01

Commercial flash memory industry has experienced a fast growth in the recent years, because of their wide spread usage in cell phones, mp3 players and digital cameras. On the other hand, there has been increased interest in the use of high density commercial nonvolatile flash memories in space because of ever increasing data requirements and strict power requirements. Because of flash memories complex structure; they cannot be treated as just simple memories in regards to testing and analysis. It becomes quite challenging to determine how they will respond in radiation environments.

Role of TGF-beta1-independent changes in protein neosynthesis, p38alphaMAPK, and cdc42 in hydrogen peroxide-induced senescence-like morphogenesis

DEFF Research Database (Denmark)

Chrétien, Aline; Dierick, Jean-François; Delaive, Edouard

2008-01-01

for p38(MAPK) activation, in turn triggering phosphorylation of L-caldesmon and HSP27. Cdc42 was also shown to be mainly responsible for the increase in TGF-beta1 mRNA level observed at 24 h after treatment with H(2)O(2) and onward. This study further clarified the mechanisms of senescence......The role of TGF-beta1 in hydrogen peroxide-induced senescence-like morphogenesis has been described. The aim of this work was to investigate whether TGF-beta1-independent changes in protein synthesis are involved in this morphogenesis and to study possible mechanisms occurring earlier than TGF-beta......1 overexpression. Among the multiple TGF-beta1-independent changes in protein neosynthesis, followed or not by posttranslational modifications, identified by proteomic analysis herein, those of ezrin, L-caldesmon, and HSP27 were particularly studied. Rho-GTPase cdc42 was shown to be responsible...

CTRP6 inhibits fibrogenesis in TGF-β1-stimulated human dermal fibroblasts

Energy Technology Data Exchange (ETDEWEB)

Fan, Rong-hui, E-mail: fan_ronghuixa@163.com [Department of Burn and Plastic Surgery, Shaanxi Provincial People’s Hospital, Xi’an 710068 (China); Zhu, Xiu-mei; Sun, Yao-wen [Department of Burn and Plastic Surgery, Shaanxi Provincial People’s Hospital, Xi’an 710068 (China); Peng, Hui-zi [Department of Cosmetology Plastic Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi 710061 (China); Wu, Hang-li; Gao, Wen-jie [Department of Burn and Plastic Surgery, Shaanxi Provincial People’s Hospital, Xi’an 710068 (China)

2016-07-08

Skin fibrosis is characterized by excessive proliferation of fibroblasts and overproduction of extracellular matrix (ECM). C1q/tumor necrosis factor-related protein 6 (CTRP6), a member of CTRPs, has been involved in the development of cardiac fibrosis. However, the function and detailed regulatory mechanism of CTRP6 in skin fibrosis remain unclear. The aim of this study was to investigate the effect of CTRP6 on the activation of human dermal fibroblasts. Our results showed that CTRP6 was lowly expressed in scar tissues and transforming growth factor-β1 (TGF-β1)-treated dermal fibroblasts. CTRP6 overexpression significantly inhibited the proliferation of dermal fibroblasts, as well as suppressed the expression of ECM in TGF-β1-treated dermal fibroblasts. Furthermore, CTRP6 overexpression markedly inhibited TGF-β1-induced phosphorylation of Smad3 in dermal fibroblasts. In conclusion, the data reported here demonstrate that CTRP6 is able to inhibit the proliferation and ECM expression in human dermal fibroblasts through suppressing the TGF-β1/Smad3 signaling pathway. These findings suggest that CTRP6 may be a potential therapeutic target for the prevention of skin fibrosis. -- Highlights: •CTRP6 expression was decreased in scar tissues and TGF-β1-treated dermal fibroblasts. •CTRP6 inhibits TGF-β1-induced the proliferation of dermal fibroblasts. •CTRP6 inhibits expression of collagen type I and α-SMA. •CTRP6 inhibits the activation of TGF-β1/Smad3 signaling pathway in dermal fibroblasts.

CTRP6 inhibits fibrogenesis in TGF-β1-stimulated human dermal fibroblasts

International Nuclear Information System (INIS)

Fan, Rong-hui; Zhu, Xiu-mei; Sun, Yao-wen; Peng, Hui-zi; Wu, Hang-li; Gao, Wen-jie

2016-01-01

Skin fibrosis is characterized by excessive proliferation of fibroblasts and overproduction of extracellular matrix (ECM). C1q/tumor necrosis factor-related protein 6 (CTRP6), a member of CTRPs, has been involved in the development of cardiac fibrosis. However, the function and detailed regulatory mechanism of CTRP6 in skin fibrosis remain unclear. The aim of this study was to investigate the effect of CTRP6 on the activation of human dermal fibroblasts. Our results showed that CTRP6 was lowly expressed in scar tissues and transforming growth factor-β1 (TGF-β1)-treated dermal fibroblasts. CTRP6 overexpression significantly inhibited the proliferation of dermal fibroblasts, as well as suppressed the expression of ECM in TGF-β1-treated dermal fibroblasts. Furthermore, CTRP6 overexpression markedly inhibited TGF-β1-induced phosphorylation of Smad3 in dermal fibroblasts. In conclusion, the data reported here demonstrate that CTRP6 is able to inhibit the proliferation and ECM expression in human dermal fibroblasts through suppressing the TGF-β1/Smad3 signaling pathway. These findings suggest that CTRP6 may be a potential therapeutic target for the prevention of skin fibrosis. -- Highlights: •CTRP6 expression was decreased in scar tissues and TGF-β1-treated dermal fibroblasts. •CTRP6 inhibits TGF-β1-induced the proliferation of dermal fibroblasts. •CTRP6 inhibits expression of collagen type I and α-SMA. •CTRP6 inhibits the activation of TGF-β1/Smad3 signaling pathway in dermal fibroblasts.

Production of bio-oils from wood by flash pyrolysis; Herstellung von Bio-Oelen aus Holz in einer Flash-Pyrolyseanlage

Energy Technology Data Exchange (ETDEWEB)

Meier, D; Ollesch, T [Bundesforschungsanstalt fuer Forst- und Holzwirtschaft, Hamburg (Germany). Inst. fuer Holzchemie und Chemische Technologie des Holzes; Gerdes, C; Kaminsky, W [Hamburg Univ. (Germany). Inst. fuer Technische und Makromolekulare Chemie (ITMCh)

1998-09-01

Flash pyrolysis is a medium-temperature process (around 475 C) in which biomass is heated up rapidly in the absence of oxygen. The pyrolysis products are cooled down rapidly, condensing into a reddish-brown liquid with around half the calorific value of a conventional heating oil. In contrast to conventional charcoal production, flash pyrolysis is a modern process whose process parameters enure high liquid yields. Modern fluidized-bed reactors for flash pyrolysis of biomass tend to have high heating rates and short times of residue. In the `Hamburg process`, fluidized-bed reactors are used successfully for pyrolysis of plastics. A flash pyrolysis plant for biomass treatment was constructed in cooperation with Hamburg University with funds provided by the `Bundesstiftung Umwelt`. This contribution describes the first series of experiments, mass balances and oil analyses using beech wood as material to be pyrolyzed. (orig./SR) [Deutsch] Flash-Pyrolyse ist ein Mitteltemperatur-Prozess (ca. 475 C), in dem Biomasse unter Sauerstoffausschluss sehr schnell erhitzt wird. Die entstehenden Pyrolyseprodukte werden schnell abgekuehlt und kondensieren zu einer roetlich-braunen Fluessigkeit, die etwa die Haelfte des Heizwertes eines konventionellen Heizoeles besitzt. Flash-Pyrolyse ist, im Gegensatz zur konventionellen Holzverkohlung, ein modernes Verfahren, dessen spezielle Verfahrensparameter hohe Fluessigausbeuten ermoeglichen. Hohe Aufheizraten, verbunden mit kurzen Verweilzeiten, werden mit stationaeren Wirbelbettreaktoren erzielt die gegenwaertig vorwiegend fuer die Flash-Pyrolyse von Biomasse eingesetzt werden. Im `Hamburger Verfahren` haben sich Wirbelbettreaktoren im Bereich der Kunststoffpyrolyse bewaehrt. Daher wurde in Zusammenarbeit mit der Universitaet Hamburg und finanzieller Foerderung der Bundesstiftung Umwelt eine Flash-Pyrolyseanlage fuer Biomasse gebaut: In dieser Arbeit werden erste Versuchsreihen, Massenbilanzen und Oelanalysen aus der Pyrolyse von

Theory of optical flashes

International Nuclear Information System (INIS)

London, R.A.

1983-01-01

The theory of optical flashes created by x- and γ-ray burst heating of stars in binaries is reviewed. Calculations of spectra due to steady-state x-ray reprocessing and estimates of the fundamental time scales for the non-steady case are discussed. The results are applied to the extant optical data from x-ray and γ-ray bursters. Finally, I review predictions of flashes from γ-ray bursters detectable by a state of the art all-sky optical monitor

Application of serum TGF-β1 determination for early diagnosis of diabetic nephropathy

International Nuclear Information System (INIS)

Jiang Zhonglin; Jiang Guoliang

2005-01-01

Objective: To investigate the feasibility of obtaining early diagnosis of diabetic nephropathy (DN) with determination of serum transforming growth factor-β 1 (TGF- β 1 ). Methods: Serum TGF-β 1 (with ELISA) and β 2 -microglobulin (β 2 -m, with RIA) levels as well as urinany β 2 -m, albumin and mciro-amount of proteins were determined in 35 controls and 84 diabetic patients with different degrees of albuminuria (Group A: urinary albumin excretion UAE 300mg/24h, n=28). Results: The serum TGF-β 1 , β 2 -m and urinary β 2 -m contents were correlated well with UAE in the diabetic patients. Conclusion: TGF-β 1 and β 2 -m were sensitive markers for early renal function injury in diabetic patients and determination of serum TGF-β 1 levels was clinically useful for diagnosis of early DN. (authors)

A cluster of coregulated genes determines TGF-β–induced regulatory T-cell (Treg) dysfunction in NOD mice

Science.gov (United States)

D'Alise, Anna Morena; Ergun, Ayla; Hill, Jonathan A.; Mathis, Diane; Benoist, Christophe

2011-01-01

Foxp3+ regulatory T cells (Tregs) originate in the thymus, but the Treg phenotype can also be induced in peripheral lymphoid organs or in vitro by stimulation of conventional CD4+ T cells with IL-2 and TGF-β. There have been divergent reports on the suppressive capacity of these TGF-Treg cells. We find that TGF-Tregs derived from diabetes-prone NOD mice, although expressing normal Foxp3 levels, are uniquely defective in suppressive activity, whereas TGF-Tregs from control strains (B6g7) or ex vivo Tregs from NOD mice all function normally. Most Treg-typical transcripts were shared by NOD or B6g7 TGF-Tregs, except for a small group of differentially expressed genes, including genes relevant for suppressive activity (Lrrc32, Ctla4, and Cd73). Many of these transcripts form a coregulated cluster in a broader analysis of T-cell differentiation. The defect does not map to idd3 or idd5 regions. Whereas Treg cells from NOD mice are normal in spleen and lymph nodes, the NOD defect is observed in locations that have been tied to pathogenesis of diabetes (small intestine lamina propria and pancreatic lymph node). Thus, a genetic defect uniquely affects a specific Treg subpopulation in NOD mice, in a manner consistent with a role in determining diabetes susceptibility. PMID:21543717

Timing in a FLASH

Science.gov (United States)

Hoek, M.; Cardinali, M.; Corell, O.; Dickescheid, M.; Ferretti B., M. I.; Lauth, W.; Schlimme, B. S.; Sfienti, C.; Thiel, M.

2017-12-01

A prototype detector, called FLASH (Fast Light Acquiring Start Hodoscope), was built to provide precise Time-of-Flight (TOF) measurements and reference timestamps for detector setups at external beam lines. Radiator bars, made of synthetic fused silica, were coupled to a fast MCP-PMT with 64 channels and read out with custom electronics using Time-over-Threshold (TOT) for signal characterization. The TRB3 system, a high-precision TDC implemented in an FPGA, was used as data acquisition system. The performance of a system consisting of two FLASH units was investigated at a dedicated test experiment at the Mainz Microtron (MAMI) accelerator using its 855 MeV electron beam. The TOT measurement enabled time walk corrections and an overall TOF resolution of ∼70 ps could be achieved which translates into a resolution of ∼50 ps per FLASH unit. The intrinsic resolution of the frontend electronics including the TDC was measured to be less than 25 ps.

Expression profiling of genes regulated by TGF-beta: Differential regulation in normal and tumour cells

Directory of Open Access Journals (Sweden)

Takahashi Takashi

2007-04-01

Full Text Available Abstract Background TGF-beta is one of the key cytokines implicated in various disease processes including cancer. TGF-beta inhibits growth and promotes apoptosis in normal epithelial cells and in contrast, acts as a pro-tumour cytokine by promoting tumour angiogenesis, immune-escape and metastasis. It is not clear if various actions of TGF-beta on normal and tumour cells are due to differential gene regulations. Hence we studied the regulation of gene expression by TGF-beta in normal and cancer cells. Results Using human 19 K cDNA microarrays, we show that 1757 genes are exclusively regulated by TGF-beta in A549 cells in contrast to 733 genes exclusively regulated in HPL1D cells. In addition, 267 genes are commonly regulated in both the cell-lines. Semi-quantitative and real-time qRT-PCR analysis of some genes agrees with the microarray data. In order to identify the signalling pathways that influence TGF-beta mediated gene regulation, we used specific inhibitors of p38 MAP kinase, ERK kinase, JNK kinase and integrin signalling pathways. The data suggest that regulation of majority of the selected genes is dependent on at least one of these pathways and this dependence is cell-type specific. Interestingly, an integrin pathway inhibitor, RGD peptide, significantly affected TGF-beta regulation of Thrombospondin 1 in A549 cells. Conclusion These data suggest major differences with respect to TGF-beta mediated gene regulation in normal and transformed cells and significant role of non-canonical TGF-beta pathways in the regulation of many genes by TGF-beta.

A Comparative Study of Reduced-Variables-Based Flash and Conventional Flash

DEFF Research Database (Denmark)

Yan, Wei; Stenby, Erling Halfdan; Michelsen, Michael Locht

2013-01-01

) with zero binary-interaction parameters (BIPs) and later generalized to situations with nonzero-BIP matrices. Most of the studies in the last decade suggest that the reduced-variables methods are much more efficient than the conventional flash method. However, Haugen and Beckner (2011) questioned...... with the conventional minimization-based flash. A test with the use of the SPE 3 example (Kenyon and Behie 1987) showed that the best reduction in time was less than 20% for the extreme situation of 25 components and just one row/column with nonzero BIPs. A better performance can be achieved by a simpler implementation...... directly using the sparsity of the BIP matrix....

Immobilized Metal Affinity Chromatography Co-Purifies TGF-β1 with Histidine-Tagged Recombinant Extracellular Proteins

Science.gov (United States)

Kaur, Jasvir; Reinhardt, Dieter P.

2012-01-01

Extracellular recombinant proteins are commonly produced using HEK293 cells as histidine-tagged proteins facilitating purification by immobilized metal affinity chromatography (IMAC). Based on gel analyses, this one-step purification typically produces proteins of high purity. Here, we analyzed the presence of TGF-β1 in such IMAC purifications using recombinant extracellular fibrillin-1 fragments as examples. Analysis of various purified recombinant fibrillin-1 fragments by ELISA consistently revealed the presence of picomolar concentrations of active and latent TGF-β1, but not of BMP-2. These quantities of TGF-β1 were not detectable by Western blotting and mass spectrometry. However, the amounts of TGF-β1 were sufficient to consistently trigger Smad2 phosphorylation in fibroblasts. The purification mechanism was analyzed to determine whether the presence of TGF-β1 in these protein preparations represents a specific or non-specific co-purification of TGF-β1 with fibrillin-1 fragments. Control purifications using conditioned medium from non-transfected 293 cells yielded similar amounts of TGF-β1 after IMAC. IMAC of purified TGF-β1 and the latency associated peptide showed that these proteins bound to the immobilized nickel ions. These data clearly demonstrate that TGF-β1 was co-purified by specific interactions with nickel, and not by specific interactions with fibrillin-1 fragments. Among various chromatographic methods tested for their ability to eliminate TGF-β1 from fibrillin-1 preparations, gel filtration under high salt conditions was highly effective. As various recombinant extracellular proteins purified in this fashion are frequently used for experiments that can be influenced by the presence of TGF-β1, these findings have far-reaching implications for the required chromatographic schemes and quality controls. PMID:23119075

TGF-β1 downregulates COX-2 expression leading to decrease of PGE2 production in human lung cancer A549 cells, which is involved in fibrotic response to TGF-β1.

Directory of Open Access Journals (Sweden)

Erina Takai

Full Text Available Transforming growth factor-ß1 (TGF-β1 is a multifunctional cytokine that is involved in various pathophysiological processes, including cancer progression and fibrotic disorders. Here, we show that treatment with TGF-β1 (5 ng/mL induced downregulation of cyclooxygenase-2 (COX-2, leading to reduced synthesis of prostaglandin E2 (PGE2, in human lung cancer A549 cells. Treatment of cells with specific inhibitors of COX-2 or PGE2 receptor resulted in growth inhibition, indicating that the COX-2/PGE2 pathway contributes to proliferation in an autocrine manner. TGF-β1 treatment induced growth inhibition, which was attenuated by exogenous PGE2. TGF-β1 is also a potent inducer of epithelial mesenchymal transition (EMT, a phenotype change in which epithelial cells differentiate into fibroblastoid cells. Supplementation with PGE2 or PGE2 receptor EP4 agonist PGE1-alcohol, as compared with EP1/3 agonist sulprostone, inhibited TGF-β1-induced expression of fibronectin and collagen I (extracellular matrix components. Exogenous PGE2 or PGE2 receptor agonists also suppressed actin remodeling induced by TGF-β1. These results suggest that PGE2 has an anti-fibrotic effect. We conclude that TGF-β1-induced downregulation of COX-2/PGE2 signaling is involved in facilitation of fibrotic EMT response in A549 cells.

NO signatures from lightning flashes

Science.gov (United States)

Stith, J.; Dye, J.; Ridley, B.; Laroche, P.; Defer, E.; Baumann, K.; Hübler, G.; Zerr, R.; Venticinque, M.

1999-07-01

In situ measurements of cloud properties, NO, and other trace gases were made in active thunderstorms by two research aircraft. Concurrent measurements from a three-dimensional (3-D) VHF interferometer and the 2-D National Lightning Detection Network were used to determine lightning frequency and location. The CHILL Doppler radar and the NOAA-WP-3D Orion X band Doppler radar were also used to measure storm characteristics. Two case studies from the (STERAO) Stratosphere-Troposphere Experiments: Radiation, Aerosols, and Ozone project in northeastern Colorado during the summer of 1996 are presented. Narrow spikes (0.11-0.96 km across), containing up to 19 ppbv of NO, were observed in the storms. Most were located in or downwind of electrically active regions where the NO produced by lightning would be expected. However, it was difficult to correlate individual flashes with NO spikes. A simple model of the plume of NO from lightning is used to estimate NO production from the mean mixing ratio measured in these spikes. The estimates range from 2.0×1020 to 1.0×1022 molecules of NO per meter of flash length.

An unusual characteristic "flower-like" pattern: flash suppressor burns.

Science.gov (United States)

Gurcan, Altun

2012-04-01

The case on contact shots from firearms with a flash suppressor is rare. When a rifle fitted with a flash suppressor is fired, the emerging soot-laden gas in the barrel escapes from the slits of the flash suppressor. If the shot is contact or near contact, the flash suppressor will produce a characteristic "flower-like" pattern of seared, blackened zones around the entrance. This paper presents the injury pattern of the flash suppressor in a 29-year-old man who committed suicide with a G3 automatic infantry rifle.

The Cytokine TGF-β Promotes the Development and Homeostasis of Alveolar Macrophages.

Science.gov (United States)

Yu, Xueyang; Buttgereit, Anne; Lelios, Iva; Utz, Sebastian G; Cansever, Dilay; Becher, Burkhard; Greter, Melanie

2017-11-21

Alveolar macrophages (AMs) derive from fetal liver monocytes, which colonize the lung during embryonic development and give rise to fully mature AMs perinatally. AM differentiation requires granulocyte macrophage colony-stimulating factor (GM-CSF), but whether additional factors are involved in AM regulation is not known. Here we report that AMs, in contrast to most other tissue macrophages, were also dependent on transforming growth factor-β receptor (TGF-βR) signaling. Conditional deletion of TGF-βR in mice at different time points halted the development and differentiation of AMs. In adult mice, TGF-β was also critical for AM homeostasis. The source of TGF-β was AMs themselves, indicative of an autocrine loop that promotes AM self-maintenance. Mechanistically, TGF-βR signaling resulted in upregulation of PPAR-γ, a signature transcription factor essential for the development of AMs. These findings reveal an additional layer of complexity regarding the guidance cues, which govern the genesis, maturation, and survival of AMs. Copyright © 2017 Elsevier Inc. All rights reserved.

Interplay between TGF-β signaling and receptor tyrosine kinases in tumor development.

Science.gov (United States)

Shi, Qiaoni; Chen, Ye-Guang

2017-10-01

Transforming growth factor-β (TGF-β) signaling regulates cell proliferation, differentiation, migration and death, and plays a critical role in embryogenesis and tissue homeostasis. Its deregulation results in various diseases including tumor formation. Receptor tyrosine kinases (RTKs), such as epidermal growth factor receptor (EGFR), fibroblast growth factor receptor (FGFR), vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR), also play key roles in the development and progression of many types of tumors. It has been realized that TGF-β signaling and RTK pathways interact with each other and their interplay is important for cancer development. They are mutually regulated and cooperatively modulate cell survival and migration, epithelial-mesenchymal transition, and tumor microenvironment to accelerate tumorigenesis and tumor metastasis. RTKs can modulate Smad-dependent transcription or cooperate with TGF-β to potentiate its oncogenic activity, while TGF-β signaling can in turn control RTK signaling by regulating their activities or expression. This review summarizes current understandings of the interplay between TGF-β signaling and RTKs and its influence on tumor development.

Increase in tumour permeability following TGF-? type I receptor-inhibitor treatment observed by dynamic contrast-enhanced MRI

OpenAIRE

Minowa, T; Kawano, K; Kuribayashi, H; Shiraishi, K; Sugino, T; Hattori, Y; Yokoyama, M; Maitani, Y

2009-01-01

Background: To enhance the success rate of nanocarrier-mediated chemotherapy combined with an anti-angiogenic agent, it is crucial to identify parameters for tumour vasculature that can predict a response to the treatment of the anti-angiogenic agent. Methods: To apply transforming growth factor (TGF)-? type I receptor (T?R-I) inhibitor, A-83-01, to combined therapy, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) was carried out in mice bearing colon 26 cells using gadolinium ...

TGF-β1 resulting in differential microRNA expression in bovine granulosa cells.

Science.gov (United States)

Xu, Yefen; Niu, Jiaqiang; Xi, Guangying; Niu, Xuezhi; Wang, Yuheng; Guo, Ming; Yangzong, Qiangba; Yao, Yilong; Sizhu, Suo Lang; Tian, Jianhui

2018-07-15

To explore the expression profile of the cellular miRNAs in bovine ovarian granulosa cells responding to transforming growth factor-β1 (TGF-β1), the effect of TGF-β1 on cell proliferation was firstly investigated by CCK-8 method and the results showed that there was a significant inhibitory effect on bovine granulosa cell proliferation treated with 5/10 ng/mL human recombinant TGF-β1 for 24 h compared to the control (P cells stimulated with or without 10 ng/mL human recombinant TGF-β1. A total of 13,257,248 and 138,726,391 clean reads per library were obtained from TGF-β1 and control groups, respectively. There were 498 and 499 bovine-specific exist miRNAs (exist miRNAs), 627 and 570 conserved known miRNAs (known miRNAs), and 593 and 585 predicted novel miRNAs in TGF-β1 and control groups, respectively. A total of 78 miRNAs with significant differential expression, including 39 up-regulated miRNAs and 39 down-regulated miRNAs were identified in the TGF-β1 group compared with the control. Real-time quantitative PCR analyses of bta-miR-106a and bta-miR-1434-5p showed that their up-expressions were interrupted by SB431542, an inhibitor that blocks TGFβ1/Smad signaling, which supported the sequencing data. GO analysis showed involvement of the predicted genes of the differentially expressed miRNAs in a broad spectrum of cell biological processes, cell components, and molecular functions. KEGG pathway analysis of the predicted miRNA targets further indicated that these differentially expressed miRNAs are involved in various signaling pathways, such as Wnt, MAPK, and TGF-β signaling, which might be involved in follicular development. These results provide valuable information on the composition, expression, and function of miRNAs in bovine granulosa cells responding to TGF-β1, and will aid in understanding the molecular mechanisms of TGF-β1 in granulosa cells. Copyright © 2018 Elsevier B.V. All rights reserved.

Possible role of TIEG1 as a feedback regulator of myostatin and TGF-{beta} in myoblasts

Energy Technology Data Exchange (ETDEWEB)

Miyake, Masato; Hayashi, Shinichiro; Iwasaki, Shunsuke; Chao, Guozheng; Takahashi, Hideyuki; Watanabe, Kouichi; Ohwada, Shyuichi; Aso, Hisashi [Laboratory of Functional Morphology, Department of Animal Biology, Graduate School of Agricultural Science, Tohoku University, 1-1 Tsutsumidori-Amamiyamachi, Aoba-Ku, Sendai 981-8555 (Japan); Yamaguchi, Takahiro, E-mail: ty1010@bios.tohoku.ac.jp [Laboratory of Functional Morphology, Department of Animal Biology, Graduate School of Agricultural Science, Tohoku University, 1-1 Tsutsumidori-Amamiyamachi, Aoba-Ku, Sendai 981-8555 (Japan)

2010-03-19

Myostatin and TGF-{beta} negatively regulate skeletal muscle development and growth. Both factors signal through the Smad2/3 pathway. However, the regulatory mechanism of myostatin and TGF-{beta} signaling remains unclear. TGF-{beta} inducible early gene (TIEG) 1 is highly expressed in skeletal muscle and has been implicated in the modulation of TGF-{beta} signaling. These findings prompted us to investigate the effect of TIEG1 on myostatin and TGF-{beta} signaling using C2C12 myoblasts. Myostatin and TGF-{beta} induced the expression of TIEG1 and Smad7 mRNAs, but not TIEG2 mRNA, in proliferating C2C12 cells. When differentiating C2C12 myoblasts were stimulated by myostatin, TIEG1 mRNA was up-regulated at a late stage of differentiation. In contrast, TGF-{beta} enhanced TIEG1 expression at an early stage. Overexpression of TIEG1 prevented the transcriptional activation of Smad by myostatin and TGF-{beta} in both proliferating or differentiating C2C12 cells, but the expression of Smad2 and Smad7 mRNAs was not affected. Forced expression of TIEG1 inhibited myogenic differentiation but did not cause more inhibition than the empty vector in the presence of myostatin or TGF-{beta}. These results demonstrate that TIEG1 is one possible feedback regulator of myostatin and TGF-{beta} that prevents excess action in myoblasts.

Possible role of TIEG1 as a feedback regulator of myostatin and TGF-β in myoblasts

International Nuclear Information System (INIS)

Miyake, Masato; Hayashi, Shinichiro; Iwasaki, Shunsuke; Chao, Guozheng; Takahashi, Hideyuki; Watanabe, Kouichi; Ohwada, Shyuichi; Aso, Hisashi; Yamaguchi, Takahiro

2010-01-01

Myostatin and TGF-β negatively regulate skeletal muscle development and growth. Both factors signal through the Smad2/3 pathway. However, the regulatory mechanism of myostatin and TGF-β signaling remains unclear. TGF-β inducible early gene (TIEG) 1 is highly expressed in skeletal muscle and has been implicated in the modulation of TGF-β signaling. These findings prompted us to investigate the effect of TIEG1 on myostatin and TGF-β signaling using C2C12 myoblasts. Myostatin and TGF-β induced the expression of TIEG1 and Smad7 mRNAs, but not TIEG2 mRNA, in proliferating C2C12 cells. When differentiating C2C12 myoblasts were stimulated by myostatin, TIEG1 mRNA was up-regulated at a late stage of differentiation. In contrast, TGF-β enhanced TIEG1 expression at an early stage. Overexpression of TIEG1 prevented the transcriptional activation of Smad by myostatin and TGF-β in both proliferating or differentiating C2C12 cells, but the expression of Smad2 and Smad7 mRNAs was not affected. Forced expression of TIEG1 inhibited myogenic differentiation but did not cause more inhibition than the empty vector in the presence of myostatin or TGF-β. These results demonstrate that TIEG1 is one possible feedback regulator of myostatin and TGF-β that prevents excess action in myoblasts.

An early warning system for flash floods in hyper-arid Egypt

Science.gov (United States)

Cools, J.; Vanderkimpen, P.; El Afandi, G.; Abdelkhalek, A.; Fockedey, S.; El Sammany, M.; Abdallah, G.; El Bihery, M.; Bauwens, W.; Huygens, M.

2012-02-01

An early warning system (EWS) for flash floods has been developed for part of the Sinai peninsula of Egypt, an hyper-arid area confronted with limited availability of field data, limited understanding of the response of the wadi to rainfall, and a lack of correspondence between rainfall data and observed flash flood events. This paper shows that an EWS is not a "mission impossible" when confronted with large technical and scientific uncertainties and limited data availability. Firstly, the EWS has been developed and tested based on the best available information, this being quantitative data (field measurements, simulations and remote sensing images) complemented with qualitative "expert opinion" and local stakeholders' knowledge. Secondly, a set of essential parameters has been identified to be estimated or measured under data-poor conditions. These are: (1) an inventory of past significant rainfall and flash flood events, (2) the spatial and temporal distribution of the rainfall events and (3) transmission and infiltration losses and (4) thresholds for issuing warnings. Over a period of 30 yr (1979-2010), only 20 significant rain events have been measured. Nine of these resulted in a flash flood. Five flash floods were caused by regional storms and four by local convective storms. The results for the 2010 flash flood show that 90% of the total rainfall volume was lost to infiltration and transmission losses. Finally, it is discussed that the effectiveness of an EWS is only partially determined by technological performance. A strong institutional capacity is equally important, especially skilled staff to operate and maintain the system and clear communication pathways and emergency procedures in case of an upcoming disaster.

Conjugate heat transfer effects on wall bubble nucleation in subcooled flashing flows

International Nuclear Information System (INIS)

Peterson, P.F.; Hijikata, K.

1990-01-01

A variety of models have been proposed to explain observations that large liquid superheat is required to initiate nucleation in flashing flows of subcooled liquids in nozzles, cracks and pipes. In such flows an abrupt change in the fluid temperature occurs downstream of the nucleating cavities. This paper examines the subcooling of the nucleating cavities due to conjugate heat transfer to the cold downstream fluid. This examination suggests a mechanism limiting the maximum active cavity size. Simple analysis shows that, of the total superheat required to initiate flashing, a substantial portion results from conjugate wall subcooling, which decreases the cavity vapor pressure. The specific case of flashing critical nozzle flow is examined in detail. Here boundary-layer laminarization due to the strong favorable pressure gradient aids the analysis of conjugate heat transfer

Flash release an alternative for releasing complex MEMS devices

NARCIS (Netherlands)

Deladi, S.; Krijnen, Gijsbertus J.M.; Elwenspoek, Michael Curt

2004-01-01

A novel time-saving and cost-effective release technique has been developed and is described. The physical nature of the process is explained in combination with experimental observations. The results of the flash release process are compared with those of freeze-drying and supercritical CO2

Flash memory in embedded Java programs

DEFF Research Database (Denmark)

Korsholm, Stephan Erbs

This paper introduces a Java execution environment with the capability for storing constant heap data in Flash, thus saving valuable RAM. The extension is motivated by the structure of three industrial applications which demonstrate the need for storing constant data in Flash on small embedded...

The role of TGF-β in the pathophysiology of peritoneal endometriosis.

Science.gov (United States)

Young, Vicky J; Ahmad, S F; Duncan, W Colin; Horne, Andrew W

2017-09-01

Endometriosis is estimated to affect 6-10% of women of reproductive age and it is associated with chronic pelvic pain, dysmenorrhoea and subfertility. It is currently managed surgically or medically but symptoms recur in up to 75% of cases and available medical treatments have undesirable side effects. Endometriosis is defined as the presence of endometrial tissue outside the uterus with lesions typically found on the peritoneum. The aetiology of endometriosis is uncertain but there is increasing evidence that transforming growth factor (TGF)-β plays a major role. A descriptive review was undertaken of the published literature on the expression pattern of TGF-β ligands and signalling molecules in women with and without endometriosis, and on the potential roles of TGF-β signalling in the development and progression of peritoneal endometriosis. The current understanding of the TGF-β signalling pathway is summarized. We searched the Pubmed database using the terms 'transforming growth factor beta' and 'endometriosis' for studies published between 1995 and 2016. The initial search identified 99 studies and these were used as the basic material for this review. We also extended our remit for important older publications. In addition, we searched the reference lists of studies used in this review for additional studies we judged as relevant. Studies which were included in the review focused on peritoneal endometriosis only as increasing evidence suggests that ovarian and deep endometriosis may have a differing pathophysiology. Thus, a final 95 studies were included in the review. TGF-β1 is reported to be increased in the peritoneal fluid, serum, ectopic endometrium and peritoneum of women with endometriosis compared to women without endometriosis, and TGF-β1-null mice have reduced endometriosis lesion growth when compared to their wild-type controls. Studies in mice and women have indicated that increasing levels of TGF-β ligands are associated with decreased

Proteomic Profiling of Mesenchymal Stem Cell Responses to Mechanical Strain and TGF-B1

Energy Technology Data Exchange (ETDEWEB)

Kurpinski, Kyle; Chu, Julia; Wang, Daojing; Li, Song

2009-10-12

Mesenchymal stem cells (MSCs) are a potential source of smooth muscle cells (SMCs) for constructing tissue-engineered vascular grafts. However, the details of how specific combinations of vascular microenvironmental factors regulate MSCs are not well understood. Previous studies have suggested that both mechanical stimulation with uniaxial cyclic strain and chemical stimulation with transforming growth factor {beta}1 (TGF-{beta}1) can induce smooth muscle markers in MSCs. In this study, we investigated the combined effects of uniaxial cyclic strain and TGF-{beta}1 stimulation on MSCs. By using a proteomic analysis, we found differential regulation of several proteins and genes, such as the up-regulation of TGF-{beta}1-induced protein ig-h3 (BGH3) protein levels by TGF-{beta}1 and up-regulation of calponin 3 protein level by cyclic strain. At the gene expression level, BGH3 was induced by TGF-{beta}1, but calponin 3 was not significantly regulated by mechanical strain or TGF-{beta}1, which was in contrast to the synergistic up-regulation of calponin 1 gene expression by cyclic strain and TGF-{beta}1. Further experiments with cycloheximide treatment suggested that the up-regulation of calponin 3 by cyclic strain was at post-transcriptional level. The results in this study suggest that both mechanical stimulation and TGF-{beta}1 signaling play unique and important roles in the regulation of MSCs at both transcriptional and post-transcriptional levels, and that a precise combination of microenvironmental cues may promote MSC differentiation.

Critical flashing flows in nozzles with subcooled inlet conditions

International Nuclear Information System (INIS)

Abuaf, N.; Jones, O.C. Jr.; Wu, B.J.C.

1983-01-01

Examination of a large number of experiments dealing with flashing flows in converging and converging-diverging nozzles reveals that knowledge of the flashing inception point is the key to the prediction of critical flow rates. An extension of the static flashing inception correlation of Jones [16] and Alamgir and Lienhard [17] to flowing systems has allowed the determination of the location of flashing inception in nozzle flows with subcooled inlet conditions. It is shown that in all the experiments examined with subcooled inlet regardless of the degree of inlet subcooling, flashing inception invariably occurred very close to the throat. A correlation is given to predict flashing inception in both pipes and nozzles which matches all data available, but is lacking verification in intermediate nozzle geometries where turbulence may be important. A consequence of this behavior is that the critical mass flux may be correlated to the pressure difference between the nozzle inlet and flashing inception, through a single phase liquid discharge coefficient and an accurate prediction of the flashing inception pressure at the throat. Comparison with the available experiments indicate that the predicted mass fluxes are within 5 percent of the measurements

YB-1 overexpression promotes a TGF-β1-induced epithelial–mesenchymal transition via Akt activation

International Nuclear Information System (INIS)

Ha, Bin; Lee, Eun Byul; Cui, Jun; Kim, Yosup; Jang, Ho Hee

2015-01-01

The Y-box binding protein-1 (YB-1) is a transcription/translation regulatory protein, and the expression thereof is associated with cancer aggressiveness. In the present study, we explored the regulatory effects of YB-1 during the transforming growth factor-β1 (TGF-β1)-induced epithelial-to-mesenchymal transition (EMT) in lung adenocarcinoma cells. Downregulation of YB-1 increased E-cadherin promoter activity, and upregulation of YB-1 decreased promoter activity, suggesting that the YB-1 level may be correlated with the EMT. TGF-β1 induced YB-1 expression, and TGF-β1 translocated cytosolic YB-1 into the nucleus. YB-1 overexpression promoted TGF-β1-induced downregulation of epithelial markers, upregulation of mesenchymal markers, and cell migration. Moreover, YB-1 overexpression enhanced the expression of E-cadherin transcriptional repressors via TGF-β1-induced Akt activation. Our findings afford new insights into the role played by YB-1 in the TGF-β1 signaling pathway. - Highlights: • YB-1 regulates E-cadherin expression in A549 cells. • TGF-β1 induces upregulating and nuclear localization of YB-1. • YB-1 overexpression accelerates TGF-β1-induced EMT and cell migration. • YB-1 regulates Snail and Slug expression via Akt activation

Development of a precipitation-area curve for warning criteria of short-duration flash flood

Science.gov (United States)

Bae, Deg-Hyo; Lee, Moon-Hwan; Moon, Sung-Keun

2018-01-01

This paper presents quantitative criteria for flash flood warning that can be used to rapidly assess flash flood occurrence based on only rainfall estimates. This study was conducted for 200 small mountainous sub-catchments of the Han River basin in South Korea because South Korea has recently suffered many flash flood events. The quantitative criteria are calculated based on flash flood guidance (FFG), which is defined as the depth of rainfall of a given duration required to cause frequent flooding (1-2-year return period) at the outlet of a small stream basin and is estimated using threshold runoff (TR) and antecedent soil moisture conditions in all sub-basins. The soil moisture conditions were estimated during the flooding season, i.e., July, August and September, over 7 years (2002-2009) using the Sejong University Rainfall Runoff (SURR) model. A ROC (receiver operating characteristic) analysis was used to obtain optimum rainfall values and a generalized precipitation-area (P-A) curve was developed for flash flood warning thresholds. The threshold function was derived as a P-A curve because the precipitation threshold with a short duration is more closely related to basin area than any other variables. For a brief description of the P-A curve, generalized thresholds for flash flood warnings can be suggested for rainfall rates of 42, 32 and 20 mm h-1 in sub-basins with areas of 22-40, 40-100 and > 100 km2, respectively. The proposed P-A curve was validated based on observed flash flood events in different sub-basins. Flash flood occurrences were captured for 9 out of 12 events. This result can be used instead of FFG to identify brief flash flood (less than 1 h), and it can provide warning information to decision-makers or citizens that is relatively simple, clear and immediate.

RLIM interacts with Smurf2 and promotes TGF-β induced U2OS cell migration

International Nuclear Information System (INIS)

Huang, Yongsheng; Yang, Yang; Gao, Rui; Yang, Xianmei; Yan, Xiaohua; Wang, Chenji; Jiang, Sirui; Yu, Long

2011-01-01

Highlights: → RLIM directly binds to Smurf2. → RLIM enhances TGF-β responsiveness in U2OS cells. → RLIM promotes TGF-β driven migration of osteosarcoma U2OS cells. -- Abstract: TGF-β (transforming growth factor-β), a pleiotropic cytokine that regulates diverse cellular processes, has been suggested to play critical roles in cell proliferation, migration, and carcinogenesis. Here we found a novel E3 ubiquitin ligase RLIM which can directly bind to Smurf2, enhancing TGF-β responsiveness in osteosarcoma U2OS cells. We constructed a U2OS cell line stably over-expressing RLIM and demonstrated that RLIM promoted TGF-β-driven migration of U2OS cells as tested by wound healing assay. Our results indicated that RLIM is an important positive regulator in TGF-β signaling pathway and cell migration.

TGF-beta3 is expressed in taste buds and inhibits proliferation of primary cultured taste epithelial cells.

Science.gov (United States)

Nakamura, Shin-ichi; Kawai, Takayuki; Kamakura, Takashi; Ookura, Tetsuya

2010-01-01

Transforming growth factor-betas (TGF-betas), expressed in various tissues, play important roles in embryonic development and adult tissue homeostasis through their effects on cell proliferation, cell differentiation, cell death, and cell motility. However, expression of TGF-beta signaling components and their biological effect on taste epithelia has not been elucidated. We performed expression analysis of TGF-beta signaling components in taste epithelia and found that the TGF-beta3 mRNA was specifically expressed in taste buds. Type II TGF-betas receptor (TbetaR-II) mRNA was specifically expressed in the tongue epithelia including the taste epithelia. To elucidate the biological function of TGF-beta3 in taste epithelia, we performed proliferation assay with primary cultured taste epithelial cells. In the presence of TGF-beta3, percentage of BrdU-labeled cells decreased significantly, suggesting that the TGF-beta3 inhibited the proliferation of cultured taste epithelial cells through inhibiting cell-cycle entry into S phase. By quantitative reverse transcription-polymerase chain reaction assay, we found that the TGF-beta3 resulted in an increased level of expression of p15Ink4b and p21Cip1, suggesting that the TGF-beta3 inhibited the taste epithelial cell proliferation through inhibiting G1cyclin-Cdk complexes. Taken together, these results suggested that the TGF-beta3 may regulate taste epithelial cell homeostasis through controlling cell proliferation.

TGF-b2 induction regulates invasiveness of Theileria-transformed leukocytes and disease susceptibility.

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Marie Chaussepied

2010-11-01

Full Text Available Theileria parasites invade and transform bovine leukocytes causing either East Coast fever (T. parva, or tropical theileriosis (T. annulata. Susceptible animals usually die within weeks of infection, but indigenous infected cattle show markedly reduced pathology, suggesting that host genetic factors may cause disease susceptibility. Attenuated live vaccines are widely used to control tropical theileriosis and attenuation is associated with reduced invasiveness of infected macrophages in vitro. Disease pathogenesis is therefore linked to aggressive invasiveness, rather than uncontrolled proliferation of Theileria-infected leukocytes. We show that the invasive potential of Theileria-transformed leukocytes involves TGF-b signalling. Attenuated live vaccine lines express reduced TGF-b2 and their invasiveness can be rescued with exogenous TGF-b. Importantly, infected macrophages from disease susceptible Holstein-Friesian (HF cows express more TGF-b2 and traverse Matrigel with great efficiency compared to those from disease-resistant Sahiwal cattle. Thus, TGF-b2 levels correlate with disease susceptibility. Using fluorescence and time-lapse video microscopy we show that Theileria-infected, disease-susceptible HF macrophages exhibit increased actin dynamics in their lamellipodia and podosomal adhesion structures and develop more membrane blebs. TGF-b2-associated invasiveness in HF macrophages has a transcription-independent element that relies on cytoskeleton remodelling via activation of Rho kinase (ROCK. We propose that a TGF-b autocrine loop confers an amoeboid-like motility on Theileria-infected leukocytes, which combines with MMP-dependent motility to drive invasiveness and virulence.

Determination of the Global-Average Charge Moment of a Lightning Flash Using Schumann Resonances and the LIS/OTD Lightning Data

Science.gov (United States)

Boldi, Robert; Williams, Earle; Guha, Anirban

2018-01-01

In this paper, we use (1) the 20 year record of Schumann resonance (SR) signals measured at West Greenwich Rhode Island, USA, (2) the 19 year Lightning Imaging Sensor (LIS)/Optical Transient Detector (OTD) lightning data, and (3) the normal mode equations for a uniform cavity model to quantify the relationship between the observed Schumann resonance modal intensity and the global-average vertical charge moment change M (C km) per lightning flash. This work, by integrating SR measurements with satellite-based optical measurements of global flash rate, accomplishes this quantification for the first time. To do this, we first fit the intensity spectra of the observed SR signals to an eight-mode, three parameter per mode, (symmetric) Lorentzian line shape model. Next, using the LIS/OTD lightning data and the normal mode equations for a uniform cavity model, we computed the expected climatological-daily-average intensity spectra. We then regressed the observed modal intensity values against the expected modal intensity values to find the best fit value of the global-average vertical charge moment change of a lightning flash (M) to be 41 C km per flash with a 99% confidence interval of ±3.9 C km per flash, independent of mode. Mode independence argues that the model adequately captured the modal intensity, the most important fit parameter herein considered. We also tested this relationship for the presence of residual modal intensity at zero lightning flashes per second and found no evidence that modal intensity is significantly different than zero at zero lightning flashes per second, setting an upper limit to the amount of nonlightning contributions to the observed modal intensity.

Yougui Pills Attenuate Cartilage Degeneration via Activation of TGF-β/Smad Signaling in Chondrocyte of Osteoarthritic Mouse Model.

Science.gov (United States)

Zhang, Lei; Wang, Ping-Er; Ying, Jun; Jin, Xing; Luo, Cheng; Xu, Taotao; Xu, Shibing; Dong, Rui; Xiao, Luwei; Tong, Peijian; Jin, Hongting

2017-01-01

Yougui pills (YGPs) have been used for centuries in the treatment of Chinese patients with Kidney-Yang Deficiency Syndrome. Despite the fact that the efficiency of YGPs on treating osteoarthritis has been verified in clinic, the underlying mechanisms are not totally understood. The present study observes the therapeutic role of YGPs and mechanisms underlying its chondroprotective action in osteoarthritic cartilage. To evaluate the chondroprotective effects of YGPs, we examined the impact of orally administered YGPs in a model of destabilization of the medial meniscus (DMM). Male C57BL/6J mice were provided a daily treatment of YGPs and a DMM surgery was performed on the right knee. At 12 weeks post-surgery, the joints were harvested for tissue analyses, including histomorphometry, OARSI scoring, micro-CT and immunohistochemistry for COL-2, MMP-13 and pSMAD-2. We also performed the relative experiments mentioned above in mice with Tgfbr2 conditional knockout ( TGF-βRII Col2ER mice) in articular cartilage. To evaluate the safety of YGPs, hematology was determined in each group. Amelioration of cartilage degradation was observed in the YGPs group, with increases in cartilage area and thickness, proteoglycan matrix, and decreases in OARSI score at 12 weeks post surgery. In addition, reduced BV/TV and Tb. Th, and elevated Tb. Sp were observed in DMM-induced mice followed by YGPs treatment. Moreover, the preservation of cartilage correlated with reduced MMP-13, and elevated COL-2 and pSMAD-2 protein expressional levels were also revealed in DMM-induced mice treated with YGPs. Similarly, TGF-βRII Col2ER mice exhibited significant OA-like phenotype. However, no significant difference in cartilage structure was observed in TGF-βRII Col2ER mice after YGPs treatment. Interestingly, no obvious adverse effects were observed in mice from each group based on the hematologic analyses. These findings suggested that YGPs could inhibit cartilage degradation through enhancing TGF

TGF-β1 and granulocyte elastase in the evaluation of activity of inflammatory bowel disease. A pilot study

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Irena Ciećko-Michalska

2014-01-01

Full Text Available Introduction: The aim was to assess the usefulness of TGF-β1 and elastase in the evaluation of activity of ulcerative colitis (UC and Crohn’s disease (CD.Material and Methods: 32 patients diagnosed with UC, 31 with CD and 30 healthy volunteers were enrolled in this study. Diagnosis of the disease was confirmed by videocolonoscopy and histopathological evaluation of intestinal biopsies. Disease activity was assessed by use of the Mayo Scoring System for Assessment of Ulcerative Colitis Activity in UC patients and by CDAI in CD patients. hsCRP was determined by the immunonephelometric method, TGF-β1 and elastase plasma concentration by ELISA. The results of the study were analyzed using Statistica and R statistical language.Results: In UC a positive correlation between disease activity and platelet level, hsCRP and TGF-β1 concentration was noted. Elastase concentration in UC patients was significantly higher than in CD, but there was no correlation with the activity of the disease. In CD patients we observed a positive correlation between disease activity and leukocytes, platelet levels and elastase concentration, and a very low correlation with hsCRP and TGF-β1.Discussion: Determination of TGF-β1 can be used for evaluation of inflammatory activity in UC and it is connected with elevated concentrations of CRP and platelets. To a lower extent TGF-β1 can also be used for evaluation of inflammatory activity in CD. Examination of elastase concentration may be useful in the assessment of CD activity. Plasma elastase concentration may be helpful in UC and CD differentiation. The preliminary results of this investigation seem promising; nevertheless, more studies are necessary.

Expression of podoplanin and TGF-beta in glandular odontogenic cyst and its comparison with developmental and inflammatory odontogenic cystic lesions.

Science.gov (United States)

Alaeddini, Mojgan; Eshghyar, Nosratollah; Etemad-Moghadam, Shahroo

2017-01-01

The number of studies investigating the immunohistochemical characteristics of glandular odontogenic cysts (GOCs) is limited, due to its rarity. TGF-beta has been suggested to induce podoplanin expression in some lesions. We aimed to evaluate and compare podoplanin and TGF-beta expression in GOC and other odontogenic cystic lesions. A total of 43 samples including five GOCs, 10 dentigerous cysts (DCs), eight unicystic ameloblastoma (UAs), and 20 radicular cysts (RCs) were selected and subjected to immunohistochemical staining using monoclonal antibodies against podoplanin and TGF-beta. Kruskal-Wallis test and Mann-Whitney U-test were used for statistical analysis along with Bonferroni for adjusting P-values (P < 0.05). Podoplanin immunoreactivity was observed in 80%, 70%, and 100% of DCs, RCs, and UAs, respectively, while none of the GOCs were positive for this marker (P = 0.004). Significant differences were only found in the GOC specimens. TGF-beta positivity occurred in the capsule and epithelium of all GOCs and DCs, while RCs and UAs demonstrated different expression percentages in the capsular and epithelial tissues. Epithelial TGF-beta showed significant differences among the studied lesions (P = 0.007) with the main difference found between DCs with RCs and DCs with UAs. Lack of podoplanin expression might be involved in the characteristic histologic and behavioral features of GOC, which seems to be unrelated to TGF-beta expression. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Flash-flood impacts cause changes in wood anatomy of Alnus glutinosa, Fraxinus angustifolia and Quercus pyrenaica.

Science.gov (United States)

Ballesteros, J A; Stoffel, M; Bollschweiler, M; Bodoque, J M; Díez-Herrero, A

2010-06-01

Flash floods may influence the development of trees growing on channel bars and floodplains. In this study, we analyze and quantify anatomical reactions to wounding in diffuse-porous (Alnus glutinosa L.) and ring-porous (Fraxinus angustifolia Vahl. and Quercus pyrenaica Willd.) trees in a Mediterranean environment. A total of 54 cross-sections and wedges were collected from trees that had been injured by past flash floods. From each of the samples, micro-sections were prepared at a tangential distance of 1.5 cm from the injury to determine wounding-related changes in radial width, tangential width and lumen of earlywood vessels, and fibers and parenchyma cells (FPC). In diffuse-porous A. glutinosa, the lumen area of vessels shows a significant (non-parametric test, P-value <0.05) decrease by almost 39% after wounding. For ring-porous F. angustifolia and Q. pyrenaica, significant decreases in vessel lumen area are observed as well by 59 and 42%, respectively. Radial width of vessels was generally more sensitive to the decrease than tangential width, but statistically significant values were only observed in F. angustifolia. Changes in the dimensions of earlywood FPC largely differed between species. While in ring-porous F. angustifolia and Q. pyrenaica the lumen of FPC dropped by 22 and 34% after wounding, we observed an increase in FPC lumen area in diffuse-porous A. glutinosa of approximately 35%. Our data clearly show that A. glutinosa represents a valuable species for flash-flood research in vulnerable Mediterranean environments. For this species, it will be possible in the future to gather information on past flash floods with non-destructive sampling based on increment cores. In ring-porous F. angustifolia and Q. pyrenaica, flash floods leave less drastic, yet still recognizable, signatures of flash-flood activity through significant changes in vessel lumen area. In contrast, the use of changes in FPC dimensions appears less feasible for the determination of

DMPD: TGF-beta signaling from receptors to the nucleus. [Dynamic Macrophage Pathway CSML Database

Lifescience Database Archive (English)

Full Text Available 10611754 TGF-beta signaling from receptors to the nucleus. Roberts AB. Microbes Inf...ect. 1999 Dec;1(15):1265-73. (.png) (.svg) (.html) (.csml) Show TGF-beta signaling from receptors to the nucleus.... PubmedID 10611754 Title TGF-beta signaling from receptors to the nucleus. Authors Roberts AB. Publicat

Risk of long-term hot flashes after natural menopause: evidence from the Penn Ovarian Aging Study cohort.

Science.gov (United States)

Freeman, Ellen W; Sammel, Mary D; Sanders, Richard J

2014-09-01

This study aims to estimate the risk of hot flashes relative to natural menopause and to evaluate the associations of hormone levels, behavioral variables, and demographic variables with the risk of hot flashes after menopause. We performed annual assessment of 255 women who were premenopausal at baseline and reached natural menopause within 16 years of follow-up. The prevalence of moderate/severe hot flashes increased in each premenopausal year, reaching a peak of 46% in the first 2 years after the final menstrual period (FMP). Hot flashes decreased slowly after menopause and did not return to premenopausal levels until 9 years after the FMP. The mean (SD) duration of moderate/severe hot flashes after the FMP was 4.6 (2.9) years (for any hot flashes, 4.9 [3.1] y). One third of women at 10 years or more after menopause continued to experience moderate/severe hot flashes. African-American women (obese and nonobese) and obese white women had significantly greater risks of hot flashes compared with nonobese white women (interaction, P = 0.01). In multivariable analysis, increasing follicle-stimulating hormone levels before the FMP (P menopause; more than one third of women observed for 10 years or more after menopause have moderate/severe hot flashes. Continuation of hot flashes for more than 5 years after menopause underscores the importance of determining individual risks/benefits when selecting hormone or nonhormone therapy for menopausal symptoms.

Frequency and seasonality of flash floods in Slovenia

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Trobec Tajan

2017-01-01

Full Text Available The purpose of this paper is to assess and analyse the dynamics of flash flooding events in Slovenia. The paper examines in particular the frequency of flash floods and their seasonal distribution. The methodology is based on the analysis of historical records and modern flood data. The results of a long-term frequency analysis of 138 flash floods that occurred between 1550 and 2015 are presented. Because of the lack of adequate historical flood data prior to 1950 the main analysis is based on data for the periodbetween1951 and2015, while the analysis of data for the period between1550 and1950 is added as a supplement to the main analysis. Analysis of data for the period after 1950 shows that on average 1.3 flash floods occur each year in Slovenia. The linear trend for the number of flash floods is increasing but is not statistically significant. Despite the fact that the majority of Slovenian rivers have one of the peaks in spring and one of the lows in summer, 90% of flash floods actually occur during meteorological summer or autumn - i.e. between June and November, which shows that discharge regimes and flood regimes are not necessarily related. Because of the lack of flood records from the more distant past as well as the large variability of flash flood events in the last several decades, we cannot provide a definitive answer to the question about possible changes in their frequency and seasonality by relying solely on the detected trends. Nevertheless, considering the results of analysis and future climate change scenarios the frequency of flash floods in Slovenia could increase while the period of flash flood occurrence could be extended.

Update on The Ultra-Fast Flash Observatory (UFFO) Pathfinder

DEFF Research Database (Denmark)

Grossan, B.; Brandt, Søren; Budtz-Jørgensen, Carl

2011-01-01

The Ultra-Fast Flash Observatory (UFFO) uses an X/gamma and an optical/UV instrument to observe gamma-ray bursts (GRB) starting milliseconds after burst trigger and location. The X/gamma instrument, a standard coded-mask camera, locates the GRB and triggers the system. The optical/UV instrument, ...

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

Science.gov (United States)

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

2015-01-06

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

Comparison of TNF-α and TGF-β1 level in radicular cyst and odontogenic keratocyst fluid and its association with histopathological findings

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Safoura Seifi

2013-09-01

Full Text Available Background: TNF-α is a multifunctional proinflammatory cytokine and TGF-β1 is a secretory protein controlling epithelial proliferation and differentiation. Keratocyst presents an aggressive behavior and a growth mechanism different from that of radicular cyst. Aim: In this line, the present study aimed at evaluating TNF-α and TGF-β1 level and its association with histopathological findings in the two odontogenic lesions of different origins. Materials and Methods: In this case-control study, aspirated fluid of 15 cases of radicular cyst and 15 cases of keratocyst were investigated using ELISA method. The grade of inflammation and the mean number of blood vessels in three microscopic fields were provided with a magnification of 40 times on microscope slides. T-test, x2, Mann Whitney, and Pearson correlation tests were used for the comparison of TNF-α and TGF-β1 levels in the mentioned lesions and the association between cytokine levels and grade of inflammation and angiogenesis.Results: TNF-α and TGF-β1 were observed in aspirated fluid of all radicular cysts and keratocysts. Levels of TNF-α and TGF-β1 were found to be 6.72 ± 2.985 and 5.882 ± 2.985 respectively in radicular cyst fluid and 24.759 ± 94.849 and 63.38 ± 30.069 in keratocyst fluid however, no statistically significant difference was observed in terms of TNF-α (P=0.450 increasing trend in TNF-α level in radicular cyst and keratocyst was accompanied by increased inflammation and angiogenesis (P<0.001 and P=0.001. Conclusion: TNF-α and TGF-β1 are involved in the pathogenesis of radicular cyst and keratocyst. TGF-β1 level was higher in radicular cyst when compared with keratocyst however, TNF-α level was similar in the two lesions. A positive correlation was found between TNF-α level and grade of inflammation and angiogenesis.

FLASH-FLOOD MODELLING WITH ARTIFICIAL NEURAL NETWORKS USING RADAR RAINFALL ESTIMATES

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Dinu Cristian

2017-09-01

Full Text Available The use of artificial neural networks (ANNs in modelling the hydrological processes has become a common approach in the last two decades, among side the traditional methods. In regard to the rainfall-runoff modelling, in both traditional and ANN models the use of ground rainfall measurements is prevalent, which can be challenging in areas with low rain gauging station density, especially in catchments where strong focused rainfall can generate flash-floods. The weather radar technology can prove to be a solution for such areas by providing rain estimates with good time and space resolution. This paper presents a comparison between different ANN setups using as input both ground and radar observations for modelling the rainfall-runoff process for Bahluet catchment, with focus on a flash-flood observed in the catchment.

TGF-β1 Induces EMT in Bovine Mammary Epithelial Cells Through the TGFβ1/Smad Signaling Pathway

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Qing Chen

2017-08-01

Full Text Available Background/Aims: Transforming growth factor-β1 (TGF-β1 plays a crucial role in chronic inflammation in various tissues, and is related to inflammation-caused organ fibrogenesis associated with the epithelial-mesenchymal transition (EMT and the deposition of the extracellular matrix (ECM. However, the effect of TGF-β1 on bovine mammary epithelial cells (BMECs with mastitis, and its mechanism, remain unknown. Methods: We analyzed the level of TGF-β1 in inflamed mammary tissues and cells using western blotting. BMECs were treated with TGF-β1, and EMT-related gene and protein expression changes were evaluated using quantitative real-time polymerase chain reaction (qPCR, western blotting, and immunofluorescence. We also inhibited the TGF/Smad signaling pathway using a receptor inhibitor, and analyzed EMT-related protein expression by western blotting. In addition, we injected TGF-β1 into mice mammary glands to investigate whether it can cause mammary fibrosis in vivo. Results: The TGF-β1 level was up-regulated in mammary tissues with mastitis and in inducible inflammatory BMECs. TGF-β1 treatment activated the TGF/ Smad signaling pathway in BMECs during their transition to the EMT phenotype, as indicated by morphological changes from a cobblestone-like shape to a spindle-like one. TGF-β1 treatment also up-regulated the expression of α-smooth muscle actin, vimentin, and collagen I, albumin, and down-regulated the expression of E-cadherin both in mRNA level and protein level. Furthermore, TGF-β1 enhanced the gene expressions of MMP2, MMP7, and fibronectin in BMECs. TGF-β1 injection induced mice mammary infection and fibrosis. Conclusion: These findings suggested that aberrant up-regulation of TGF-β1 in bovine mastitic mammary glands might play an important role in bovine mammary fibrosis caused by unresolved inflammation.

Growth-inhibitory effect of TGF-B on human fetal adrenal cells in primary monolayer culture.

Science.gov (United States)

Riopel, L; Branchaud, C L; Goodyer, C G; Adkar, V; Lefebvre, Y

1989-08-01

We examined the effects of transforming-growth factor-B (TGF-B) on growth ([3H]-thymidine uptake) and function (dehydroepiandrosterone sulfate [DHAS] and cortisol production) of human fetal zone adrenal cells. Results indicate that TGF-B significantly inhibits, in a dose-related manner, both basal and epidermal growth factor (EGF)-stimulated cell growth: IC50 = 0.1-0.25 ng/ml. EGF is ineffective in overcoming the inhibitory effect of TGF-B, suggesting a noncompetitive antagonism between the two factors. Also, the inhibitory effect of TGF-B is additive to that of adrenocorticotropic hormone (ACTH). On the other hand, TGF-B (1 ng/ml) does not significantly change basal or ACTH-stimulated DHAS or cortisol secretion. We conclude that, unlike its effect on other steroid-producing cells, TGF-B inhibits growth of fetal zone cells and does not appear to have a significant inhibitory effect on steroidogenesis.

Menopausal Hot Flashes and Carotid Intima Media Thickness Among Midlife Women.

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Thurston, Rebecca C; Chang, Yuefang; Barinas-Mitchell, Emma; Jennings, J Richard; Landsittel, Doug P; Santoro, Nanette; von Känel, Roland; Matthews, Karen A

2016-12-01

There has been a longstanding interest in the role of menopause and its correlates in the development of cardiovascular disease (CVD) in women. Menopausal hot flashes are experienced by most midlife women; emerging data link hot flashes to CVD risk indicators. We tested whether hot flashes, measured via state-of-the-art physiologic methods, were associated with greater subclinical atherosclerosis as assessed by carotid ultrasound. We considered the role of CVD risk factors and estradiol concentrations in these associations. A total of 295 nonsmoking women free of clinical CVD underwent ambulatory physiologic hot flash assessments; a blood draw; and carotid ultrasound measurement of intima media thickness and plaque. Associations between hot flashes and subclinical atherosclerosis were tested in regression models controlling for CVD risk factors and estradiol. More frequent physiologic hot flashes were associated with higher carotid intima media thickness (for each additional hot flash: β [SE]=0.004 [0.001]; P=0.0001; reported hot flash: β [SE]=0.008 [0.002]; P=0.002, multivariable) and plaque (eg, for each additional hot flash, odds ratio [95% confidence interval] plaque index ≥2=1.07 [1.003-1.14]; P=0.04, relative to no plaque, multivariable] among women reporting daily hot flashes; associations were not accounted for by CVD risk factors or by estradiol. Among women reporting hot flashes, hot flashes accounted for more variance in intima media thickness than most CVD risk factors. Among women reporting daily hot flashes, frequent hot flashes may provide information about a woman's vascular status beyond standard CVD risk factors and estradiol. Frequent hot flashes may mark a vulnerable vascular phenotype among midlife women. © 2016 American Heart Association, Inc.

Flood hazard assessment in areas prone to flash flooding

Science.gov (United States)

Kvočka, Davor; Falconer, Roger A.; Bray, Michaela

2016-04-01

Contemporary climate projections suggest that there will be an increase in the occurrence of high-intensity rainfall events in the future. These precipitation extremes are usually the main cause for the emergence of extreme flooding, such as flash flooding. Flash floods are among the most unpredictable, violent and fatal natural hazards in the world. Furthermore, it is expected that flash flooding will occur even more frequently in the future due to more frequent development of extreme weather events, which will greatly increase the danger to people caused by flash flooding. This being the case, there will be a need for high resolution flood hazard maps in areas susceptible to flash flooding. This study investigates what type of flood hazard assessment methods should be used for assessing the flood hazard to people caused by flash flooding. Two different types of flood hazard assessment methods were tested: (i) a widely used method based on an empirical analysis, and (ii) a new, physically based and experimentally calibrated method. Two flash flood events were considered herein, namely: the 2004 Boscastle flash flood and the 2007 Železniki flash flood. The results obtained in this study suggest that in the areas susceptible to extreme flooding, the flood hazard assessment should be conducted using methods based on a mechanics-based analysis. In comparison to standard flood hazard assessment methods, these physically based methods: (i) take into account all of the physical forces, which act on a human body in floodwater, (ii) successfully adapt to abrupt changes in the flow regime, which often occur for flash flood events, and (iii) rapidly assess a flood hazard index in a relatively short period of time.

Incorporating pTGF-β1/calcium phosphate nanoparticles with fibronectin into 3-dimensional collagen/chitosan scaffolds: Efficient, sustained gene delivery to stem cells for chondrogenic differentiation

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X Cao

2012-02-01

Full Text Available The objective of this study was to prepare a 3-dimensional nanoparticle gene delivery system (3D-NGDS based on collagen/chitosan scaffolds, in which plasmid transforming growth factor beta 1 (TGF-β1/calcium phosphate nanoparticles mixed with fibronectin (FN were used to transfect mesenchymal stem cells (MSCs. Scanning electron microscopy was used to characterise the microstructure of 3-dimensional collagen/chitosan scaffolds. An analysis performed to quantify the TGF-b1 concentrations in MSC cultures revealed that the MSCs transfected with the 3D-NGDS showed remarkably high levels of TGF-b1 over long periods, retaining a concentration of TGF-b1 of approximately 10 ng/mL within two weeks, with the highest level (12.6 ng/mL being observed on the 6th day. An immunohistochemistry analysis for collagen type II revealed that much higher production of collagen II from the 9th to 15th day was observed in the 3D-NGDS-transfected MSCs than that in MSCs transfected by the Lipofectamine 2000 method. The glycosaminoglycan content of the 3D-NGDS was comparable to those treated with TGF-β1 as well as TGF-β1 plus dexamethasone, and was significantly higher than those treated with free plasmid and Lipofectamine 2000. A remarkable type I collagen expression inhibition of the 3D-NGDS at day 21 was observed via ELISA. These results suggested that transfection with the 3D-NGDS could successfully induce MSC chondrogenic differentiation in vitro without dexamethasone. In summary, the 3D-NGDS could be developed into a promising alternative method to transfer exogenous nucleic acid to MSCs in clinical trials.

Plasma Gelsolin Induced Glomerular Fibrosis via the TGF-β1/Smads Signal Transduction Pathway in IgA Nephropathy

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Lei Zhang

2017-02-01

Full Text Available Glomerular fibrosis has been shown to be closely related to the progression and prognosis of IgA nephropathy (IgAN. However, mechanism underlying IgAN glomerular fibrosis remains unclear. Recently, our study showed that plasma gelsolin (pGSN was decreased in the serum of an IgAN mouse model and that pGSN deposition was found in the glomeruli. Another cytokine, TGF-β1, which is closely related to glomerular fibrosis, was also found to be highly expressed in the glomeruli. In the present study, we report that pGSN induces glomerular fibrosis through the TGF-β1/Smads signal transduction pathway. This is supported by the following findings: human mesangial cells (HMCs show remarkable morphological changes and proliferation in response to co-stimulation with pGSN and polymeric IgA1 (pIgA1 from IgAN patients compared to other controls. Moreover, ELISA assays showed that more TGF-β1 secretion was found in HMCs supernatants in the co-stimulation group. Further experiments showed increased TGF-β1, Smad3, p-Smad2/3, Smad4, and collagen 1 and decreased Smad7 expression in the co-stimulation group. Our present study implied that the synergistic effect of pGSN and pIgA induced glomerular fibrosis via the TGF-β1/Smads signal transduction pathway. This might be a potential mechanism for the glomerular fibrosis observed in IgAN patients.

Plasma Gelsolin Induced Glomerular Fibrosis via the TGF-β1/Smads Signal Transduction Pathway in IgA Nephropathy

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Zhang, Lei; Han, Changsong; Ye, Fei; He, Yan; Jin, Yinji; Wang, Tianzhen; Wu, Yiqi; Jiang, Yang; Zhang, Fengmin; Jin, Xiaoming

2017-01-01

Glomerular fibrosis has been shown to be closely related to the progression and prognosis of IgA nephropathy (IgAN). However, mechanism underlying IgAN glomerular fibrosis remains unclear. Recently, our study showed that plasma gelsolin (pGSN) was decreased in the serum of an IgAN mouse model and that pGSN deposition was found in the glomeruli. Another cytokine, TGF-β1, which is closely related to glomerular fibrosis, was also found to be highly expressed in the glomeruli. In the present study, we report that pGSN induces glomerular fibrosis through the TGF-β1/Smads signal transduction pathway. This is supported by the following findings: human mesangial cells (HMCs) show remarkable morphological changes and proliferation in response to co-stimulation with pGSN and polymeric IgA1 (pIgA1) from IgAN patients compared to other controls. Moreover, ELISA assays showed that more TGF-β1 secretion was found in HMCs supernatants in the co-stimulation group. Further experiments showed increased TGF-β1, Smad3, p-Smad2/3, Smad4, and collagen 1 and decreased Smad7 expression in the co-stimulation group. Our present study implied that the synergistic effect of pGSN and pIgA induced glomerular fibrosis via the TGF-β1/Smads signal transduction pathway. This might be a potential mechanism for the glomerular fibrosis observed in IgAN patients. PMID:28208683

miR-181b regulates vascular stiffness age dependently in part by regulating TGF-β signaling.

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Daijiro Hori

Full Text Available Endothelial dysfunction and arterial stiffening play major roles in cardiovascular diseases. The critical role for the miR-181 family in vascular inflammation has been documented. Here we tested whether the miR-181 family can influence the pathogenesis of hypertension and vascular stiffening.qPCR data showed a significant decrease in miR-181b expression in the aorta of the older mice. Eight miR-181a1/b1-/- mice and wild types (C57BL6J:WT were followed weekly for pulse wave velocity (PWV and blood pressure measurements. After 20 weeks, the mice were tested for endothelial function and aortic modulus. There was a progressive increase in PWV and higher systolic blood pressure in miR-181a1/b1-/- mice compared with WTs. At 21 weeks, aortic modulus was significantly greater in the miR-181a1/b1-/- group, and serum TGF-β was found to be elevated at this time. A luciferase reporter assay confirmed miR-181b targets TGF-βi (TGF-β induced in the aortic VSMCs. In contrast, wire myography revealed unaltered endothelial function along with higher nitric oxide production in the miR-181a1/b1-/- group. Cultured VECs and VSMCs from the mouse aorta showed more secreted TGF-β in VSMCs of the miR-181a1/b1-/- group; whereas, no change was observed from VECs. Circulating levels of angiotensin II were similar in both groups. Treatment with losartan (0.6 g/L prevented the increase in PWV, blood pressure, and vascular stiffness in miR-181a1/b1-/- mice. Immunohistochemistry and western blot for p-SMAD2/3 validated the inhibitory effect of losartan on TGF-β signaling in miR-181a1/b1-/- mice.Decreased miR-181b with aging plays a critical role in ECM remodeling by removing the brake on the TGF-β, pSMAD2/3 pathway.

Downregulation of TGF-β Receptor-2 Expression and Signaling through Inhibition of Na/K-ATPase.

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Jennifer La

Full Text Available Transforming growth factor-beta (TGF-β is a multi-functional cytokine implicated in the control of cell growth and differentiation. TGF-β signals through a complex of TGF-β receptors 1 and 2 (TGFβR1 and TGFβR2 that phosphorylate and activate Smad2/3 transcription factors driving transcription of the Smad-target genes. The Na+/K+-ATPase is an integral plasma membrane protein critical for maintaining the electro-chemical gradient of Na+ and K+ in the cell. We found that inhibition of the Na+/K+ ATPase by ouabain results in a dramatic decrease in the expression of TGFβR2 in human lung fibrobalsts (HLF at the mRNA and protein levels. This was accompanied by inhibition of TGF-β-induced Smad phosphorylation and the expression of TGF-β target genes, such as fibronectin and smooth muscle alpha-actin. Inhibition of Na+/K+ ATPase by an alternative approach (removal of extracellular potassium had a similar effect in HLF. Finally, treatment of lung alveolar epithelial cells (A549 with ouabain also resulted in the downregulation of TGFβR2, the inhibition of TGF-β-induced Smad phosphorylation and of the expression of mesenchymal markers, vimentin and fibronectin. Together, these data demonstrate a critical role of Na+/K+-ATPase in the control of TGFβR2 expression, TGF-β signaling and cell responses to TGF-β.

Flash memory management system and method utilizing multiple block list windows

Science.gov (United States)

Chow, James (Inventor); Gender, Thomas K. (Inventor)

2005-01-01

The present invention provides a flash memory management system and method with increased performance. The flash memory management system provides the ability to efficiently manage and allocate flash memory use in a way that improves reliability and longevity, while maintaining good performance levels. The flash memory management system includes a free block mechanism, a disk maintenance mechanism, and a bad block detection mechanism. The free block mechanism provides efficient sorting of free blocks to facilitate selecting low use blocks for writing. The disk maintenance mechanism provides for the ability to efficiently clean flash memory blocks during processor idle times. The bad block detection mechanism provides the ability to better detect when a block of flash memory is likely to go bad. The flash status mechanism stores information in fast access memory that describes the content and status of the data in the flash disk. The new bank detection mechanism provides the ability to automatically detect when new banks of flash memory are added to the system. Together, these mechanisms provide a flash memory management system that can improve the operational efficiency of systems that utilize flash memory.

ΔNp73 enhances promoter activity of TGF-β induced genes.

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Maarten Niemantsverdriet

Full Text Available The p53 homolog p73 is frequently overexpressed in cancers. Especially the transactivation domain truncated isoform ΔNp73 has oncogenic properties and its upregulation is associated with poor patient survival. It has been shown that ΔNp73 has an inhibitory effect on the transactivation capacity of p53 and other p73 isoforms. Here, we confirm this finding but surprisingly find that ΔNp73 may also stimulate the expression of TGF-β signaling targets. Promoter-reporter analysis indicated that the presence of Smad Binding Elements (SBE in the promoter is sufficient for stimulation of gene expression by ΔNp73. TGF-β signaling was less efficient in ΔNp73 downregulated cells, whereas tetracycline induced ΔNp73 increased expression of endogenous TGF-β regulated genes PAI-1 and Col1a1. Pull-down assays with SBE DNA suggest that ΔNp73 enhances smad3/4 binding to SBEs, thereby stimulating TGF-β signaling. Chromatin immunoprecipitation assays confirmed a direct interaction between ΔNp73 and SBE. Given the role of TGF-β signaling in carcinogenesis, tumor invasion and metastasis via targets like PAI-1 and Col1a1, our data suggest a model on how this effect of ΔNp73 could be a contributing factor in cancer progression.

Induction of CTGF by TGF-β1 in normal and radiation enteritis human smooth muscle cells: Smad/Rho balance and therapeutic perspectives

International Nuclear Information System (INIS)

Haydont, Valerie; Mathe, Denis; Bourgier, Celine; Abdelali, Jalil; Aigueperse, Jocelyne; Bourhis, Jean; Vozenin-Brotons, Marie-Catherine

2005-01-01

Background and purpose: Transforming Growth Factor β1 (TGF-β1) and its downstream effector Connective Tissue Growth Factor (CTGF/CCN2), are well known fibrogenic activators and we previously showed that the Rho/ROCK pathway controls CTGF expression in intestinal smooth muscle cells isolated from patients with delayed radiation enteritis. The aim of the present work was to investigate the balance between Smad and Rho signalling pathways in the TGF-β1 CTGF induction and modulation of radiation-induced fibrogenic differentiation after addition of pravastatin, an inhibitor of Rho isoprenylation. Patients and methods: Primary human smooth muscle cells isolated from normal (N-SMC) or radiation enteritis (RE-SMC) biopsies were incubated with TGF-β1 (10 ng/ml). Induction of CTGF, as well as nucleo-cytoplasmic distribution of phospho-Smad2/3, Smad2/3 and Smad4 were analysed by Western blot and immunocytochemistry. Smad DNA binding was assessed by EMSA and Rho activation was measured by pull-down assay. Results: After TGF-β1 addition, Smads were translocated to the nucleus in both cell types. Nuclear accumulation of Smad as well as their DNA-binding activity were higher in N-SMC than in RE-SMC, whereas the opposite was observed for Rho activation, suggesting a main involvement of Rho pathway in sustained fibrogenic differentiation. This hypothesis was further supported by the antifibrotic effect observed in vitro after cell treatment with pravastatin (i.e. decreased expression of CTGF, TGF-β1 and Collagen Iα2). Conclusions: Our results suggest that TGF-β1-induced CTGF transactivation mainly depends on the Smad pathway in N-SMC, whereas in RE-SMC, Smad and Rho pathways are involved. Inhibition of Rho activity by pravastatin alters fibrogenic differentiation in vitro which opens up new therapeutic perspectives

A Mathematical Model Quantifies Proliferation and Motility Effects of TGF-β on Cancer Cells

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Shizhen Emily Wang

2009-01-01

Full Text Available Transforming growth factor (TGF-β is known to have properties of both a tumour suppressor and a tumour promoter. While it inhibits cell proliferation, it also increases cell motility and decreases cell–cell adhesion. Coupling mathematical modelling and experiments, we investigate the growth and motility of oncogene-expressing human mammary epithelial cells under exposure to TGF-β. We use a version of the well-known Fisher–Kolmogorov equation, and prescribe a procedure for its parametrisation. We quantify the simultaneous effects of TGF-β to increase the tendency of individual cells and cell clusters to move randomly and to decrease overall population growth. We demonstrate that in experiments with TGF-β treated cells in vitro, TGF-β increases cell motility by a factor of 2 and decreases cell proliferation by a factor of 1/2 in comparison with untreated cells.

Overexpression of TGF-β1 enhances chondrogenic differentiation and proliferation of human synovium-derived stem cells

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Kim, Yong Il; Ryu, Jae-Sung; Yeo, Jee Eun; Choi, Yun Jin; Kim, Yong Sang [Center for Stem Cell and Arthritis Research, Department of Orthopedic Surgery, Yonsei Sarang Hospital, Seoul (Korea, Republic of); Ko, Kinarm [Center for Stem Cell Research, Institute of Advanced Biomedical Science, Konkuk University, Seoul 143-701 (Korea, Republic of); Koh, Yong-Gon, E-mail: yonseranglab@daum.net [Center for Stem Cell and Arthritis Research, Department of Orthopedic Surgery, Yonsei Sarang Hospital, Seoul (Korea, Republic of)

2014-08-08

Highlights: • Continuous TGF-β1 overexpression in hSD-MSCs did not influence their phenotypes. • Retroviral-mediated transduction of TGFB1 in hSD-MSCs enhances cell proliferation. • TGF-β1 overexpression did not effect to adipo- or osteogenic potential of hSD-MSCs. • TGF-β1 overexpression in hSD-MSCs could stimulate and accelerate chondrogenesis. - Abstract: Transforming growth factor-beta (TGF-β) superfamily proteins play a critical role in proliferation, differentiation, and other functions of mesenchymal stem cells (MSCs). During chondrogenic differentiation of MSCs, TGF-β up-regulates chondrogenic gene expression by enhancing the expression of the transcription factor SRY (sex-determining region Y)-box9 (Sox9). In this study, we investigated the effect of continuous TGF-β1 overexpression in human synovium-derived MSCs (hSD-MSCs) on immunophenotype, differentiation potential, and proliferation rate. hSD-MSCs were transduced with recombinant retroviruses (rRV) encoding TGF-β1. The results revealed that continuous overexpression of TGF-β1 did not affect their phenotype as evidenced by flow cytometry and reverse transcriptase PCR (RT-PCR). In addition, continuous TGF-β1 overexpression strongly enhanced cell proliferation of hSD-MSCs compared to the control groups. Also, induction of chondrogenesis was more effective in rRV-TGFB-transduced hSD-MSCs as shown by RT-PCR for chondrogenic markers, toluidine blue staining and glycosaminoglycan (GAG)/DNA ratio. Our data suggest that overexpression of TGF-β1 positively enhances the proliferation and chondrogenic potential of hSD-MSCs.

Overexpression of TGF-β1 enhances chondrogenic differentiation and proliferation of human synovium-derived stem cells

International Nuclear Information System (INIS)

Kim, Yong Il; Ryu, Jae-Sung; Yeo, Jee Eun; Choi, Yun Jin; Kim, Yong Sang; Ko, Kinarm; Koh, Yong-Gon

2014-01-01

Highlights: • Continuous TGF-β1 overexpression in hSD-MSCs did not influence their phenotypes. • Retroviral-mediated transduction of TGFB1 in hSD-MSCs enhances cell proliferation. • TGF-β1 overexpression did not effect to adipo- or osteogenic potential of hSD-MSCs. • TGF-β1 overexpression in hSD-MSCs could stimulate and accelerate chondrogenesis. - Abstract: Transforming growth factor-beta (TGF-β) superfamily proteins play a critical role in proliferation, differentiation, and other functions of mesenchymal stem cells (MSCs). During chondrogenic differentiation of MSCs, TGF-β up-regulates chondrogenic gene expression by enhancing the expression of the transcription factor SRY (sex-determining region Y)-box9 (Sox9). In this study, we investigated the effect of continuous TGF-β1 overexpression in human synovium-derived MSCs (hSD-MSCs) on immunophenotype, differentiation potential, and proliferation rate. hSD-MSCs were transduced with recombinant retroviruses (rRV) encoding TGF-β1. The results revealed that continuous overexpression of TGF-β1 did not affect their phenotype as evidenced by flow cytometry and reverse transcriptase PCR (RT-PCR). In addition, continuous TGF-β1 overexpression strongly enhanced cell proliferation of hSD-MSCs compared to the control groups. Also, induction of chondrogenesis was more effective in rRV-TGFB-transduced hSD-MSCs as shown by RT-PCR for chondrogenic markers, toluidine blue staining and glycosaminoglycan (GAG)/DNA ratio. Our data suggest that overexpression of TGF-β1 positively enhances the proliferation and chondrogenic potential of hSD-MSCs

TGF{beta} induces proHB-EGF shedding and EGFR transactivation through ADAM activation in gastric cancer cells

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Ebi, Masahide [Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya (Japan); Kataoka, Hiromi, E-mail: hkataoka@med.nagoya-cu.ac.jp [Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya (Japan); Shimura, Takaya; Kubota, Eiji; Hirata, Yoshikazu; Mizushima, Takashi; Mizoshita, Tsutomu; Tanaka, Mamoru; Mabuchi, Motoshi; Tsukamoto, Hironobu; Tanida, Satoshi; Kamiya, Takeshi [Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya (Japan); Higashiyama, Shigeki [Department of Biochemistry and Molecular Genetics, Ehime University Graduate School of Medicine, Ehime (Japan); Joh, Takashi [Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya (Japan)

2010-11-19

Research highlights: {yields} TGF{beta} induces EGFR transactivation through proHB-EGF shedding by activated ADAM members in gastric cancer cells. {yields} TGF{beta} induces nuclear translocation of HB-EGF-CTF cleaved by ADAM members. {yields} TGF{beta} enhances cell growth by EGFR transactivation and HB-EGF-CTF nuclear translocation and ADAM inhibitors block these effects. {yields} Silencing of ADAM17 also blocks EGFR transactivation, HB-EGF-CTF nuclear translocation and cancer cell growth by TGF{beta}. {yields} ADAM17 may play a crucial role in this TGF{beta}-HB-EGF signal transduction. -- Abstract: Background and aims: Transforming growth factor-beta (TGF{beta}) is known to potently inhibit cell growth. Loss of responsiveness to TGF{beta} inhibition on cell growth is a hallmark of many types of cancer, yet its mechanism is not fully understood. Membrane-anchored heparin-binding EGF-like growth factor (proHB-EGF) ectodomain is cleaved by a disintegrin and metalloproteinase (ADAM) members and is implicated in epidermal growth factor receptor (EGFR) transactivation. Recently, nuclear translocation of the C-terminal fragment (CTF) of pro-HB-EGF was found to induce cell growth. We investigated the association between TGF{beta} and HB-EGF signal transduction via ADAM activation. Materials and methods: The CCK-8 assay in two gastric cancer cell lines was used to determine the effect for cell growth by TGF{beta}. The effect of two ADAM inhibitors was also evaluated. Induction of EGFR phosphorylation by TGF{beta} was analyzed and the effect of the ADAM inhibitors was also examined. Nuclear translocation of HB-EGF-CTF by shedding through ADAM activated by TGF{beta} was also analyzed. EGFR transactivation, HB-EGF-CTF nuclear translocation, and cell growth were examined under the condition of ADAM17 knockdown. Result: TGF{beta}-induced EGFR phosphorylation of which ADAM inhibitors were able to inhibit. TGF{beta} induced shedding of proHB-EGF allowing HB-EGF-CTF to

TGF-β's delay skeletal muscle progenitor cell differentiation in an isoform-independent manner

International Nuclear Information System (INIS)

Schabort, Elske J.; Merwe, Mathilde van der; Loos, Benjamin; Moore, Frances P.; Niesler, Carola U.

2009-01-01

Satellite cells are a quiescent heterogenous population of mononuclear stem and progenitor cells which, once activated, differentiate into myotubes and facilitate skeletal muscle repair or growth. The Transforming Growth Factor-β (TGF-β) superfamily members are elevated post-injury and their importance in the regulation of myogenesis and wound healing has been demonstrated both in vitro and in vivo. Most studies suggest a negative role for TGF-β on satellite cell differentiation. However, none have compared the effect of these three isoforms on myogenesis in vitro. This is despite known isoform-specific effects of TGF-β1, -β2 and -β3 on wound repair in other tissues. In the current study we compared the effect of TGF-β1, -β2 and -β3 on proliferation and differentiation of the C2C12 myoblast cell-line. We found that, irrespective of the isoform, TGF-β increased proliferation of C2C12 cells by changing the cellular localisation of PCNA to promote cell division and prevent cell cycle exit. Concomitantly, TGF-β1, -β2 and -β3 delayed myogenic commitment by increasing MyoD degradation and decreasing myogenin expression. Terminal differentiation, as measured by a decrease in myosin heavy chain (MHC) expression, was also delayed. These results demonstrate that TGF-β promotes proliferation and delays differentiation of C2C12 myoblasts in an isoform-independent manner

Iro/IRX transcription factors negatively regulate Dpp/TGF-β pathway activity during intestinal tumorigenesis.

Science.gov (United States)

Martorell, Òscar; Barriga, Francisco M; Merlos-Suárez, Anna; Stephan-Otto Attolini, Camille; Casanova, Jordi; Batlle, Eduard; Sancho, Elena; Casali, Andreu

2014-11-01

Activating mutations in Wnt and EGFR/Ras signaling pathways are common in colorectal cancer (CRC). Remarkably, clonal co-activation of these pathways in the adult Drosophila midgut induces "tumor-like" overgrowths. Here, we show that, in these clones and in CRC cell lines, Dpp/TGF-β acts as a tumor suppressor. Moreover, we discover that the Iroquois/IRX-family-protein Mirror downregulates the transcription of core components of the Dpp pathway, reducing its tumor suppressor activity. We also show that this genetic interaction is conserved in human CRC cells, where the Iro/IRX proteins IRX3 and IRX5 diminish the response to TGF-β. IRX3 and IRX5 are upregulated in human adenomas, and their levels correlate inversely with the gene expression signature of response to TGF-β. In addition, Irx5 expression confers a growth advantage in the presence of TGF-β, but is selected against in its absence. Together, our results identify a set of Iro/IRX proteins as conserved negative regulators of Dpp/TGF-β activity. We propose that during the characteristic adenoma-to-carcinoma transition of human CRC, the activity of IRX proteins could reduce the sensitivity to the cytostatic effect of TGF-β, conferring a growth advantage to tumor cells prior to the acquisition of mutations in TGF-β pathway components. © 2014 The Authors.

uFlip: Understanding Flash IO Patterns

DEFF Research Database (Denmark)

Bouganim, Luc; Jonsson, Bjørn; Bonnet, Philippe

2009-01-01

want to establish what kind of IOs should be favored (or avoided) when designing algorithms and architectures for flash-based systems. In this paper, we focus on flash IO patterns, that capture relevant distribution of IOs in time and space, and our goal is to quantify their performance. We define uFLIP...

Analysis of the presence of cell proliferation-related molecules in the Tgf-β3 null mutant mouse palate reveals misexpression of EGF and Msx-1.

Science.gov (United States)

del Río, A; Barrio, M C; Murillo, J; Maldonado, E; López-Gordillo, Y; Martínez-Sanz, E; Martínez, M L; Martínez-Álvarez, C

2011-01-01

The Tgf-β(3) null mutant mouse palate presents several cellular anomalies that lead to the appearance of cleft palate. One of them concerns the cell proliferation of both the palatal medial edge epithelium and mesenchyme. In this work, our aim was to determine whether there was any variation in the presence/distribution of several cell proliferation-related molecules that could be responsible for the cell proliferation defects observed in these palates. Our results showed no difference in the presence of EGF-R, PDGF-A, TGF-β(2), Bmp-2, and Bmp-4, and differences were minimal for FGF-10 and Shh. However, the expression of EGF and Msx-1 changed substantially. The shift of the EGF protein expression was the one that most correlated with that of cell proliferation. This molecule is regulated by TGF-β(3), and experiments blocking its activity in culture suggest that EGF misexpression in the Tgf-β(3) null mutant mouse palate plays a role in the cell proliferation defect observed. Copyright © 2010 S. Karger AG, Basel.

The Role of the TGF-β Coreceptor Endoglin in Cancer

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Eduardo Pérez-Gómez

2010-01-01

Full Text Available Endoglin (CD105 is an auxiliary membrane receptor of transforming growth factor beta (TGF-β that interacts with type I and type II TGF-β receptors and modulates TGF-β signaling. Endoglin is overexpressed in the tumor-associated vascular endothelium, where it modulates angiogenesis. This feature makes endoglin a promising target for antiangiogenic cancer therapy. In addition, recent studies on human and experimental models of carcinogenesis point to an important tumor cell–autonomous role of endoglin by regulating proliferation, migration, invasion, and metastasis. These studies suggest that endoglin behaves as a suppressor of malignancy in experimental and human epithelial carcinogenesis, although it can also promote metastasis in other types of cancer. In this review, we evaluate the implication of endoglin in tumor development underlying studies developed in our laboratories in recent years.

Exploring Branded Flash Mobs : A study of the impact of branded flash mobs on consumer behavior and consumer experience

OpenAIRE

Grant, Philip

2014-01-01

The desire of every marketer is to develop and maintain strong customer relationships. One way this can be accomplished is through effective advertising. Marketers have recently begun to brand flash mobs as a way to effectuate strong brand relationships. Even so, it is unclear whether or not the branding of flash mobs supports or frustrates this pursuit. Therefore, the goal of this thesis is to help marketers understand the potential impact that branded flash mobs may have on consumer behavio...

Microphysical and Kinematic Characteristics of Regions of Flash Initiation in a Supercell Storm and a Multicell Storm Observed During the DC3 Field Program

Science.gov (United States)

DiGangi, E.; MacGorman, D. R.; Ziegler, C.; Betten, D.; Biggerstaff, M. I.

2017-12-01

Lightning initiation in thunderstorms requires that the local electric field magnitude exceed breakdown values somewhere, and this tends to occur between regions of positive and negative charge, where the largest electric field magnitudes tend to occur. Past studies have demonstrated that, near updrafts, storms with very strong updrafts tend to elevate regions of charge and of flash initiations higher, as well as to have more flashes initiated by small pockets of charge, than in storms with much weaker updrafts. In all thunderstorms, the source of these charge regions is generally thought to be microscopic charge separation via the relative growth rate noninductive mechanism, followed by macroscopic charge separation via sedimentation, although other charge generation mechanisms can contribute to charge in some regions. Charge generation and lightning initiation are therefore inherently dependent on the microphysical and kinematic characteristics of a given storm. This study compares the results of a hydrometeor classification algorithm applied to C-band mobile radar data with mixing ratios calculated by a diabatic Lagrangian analysis retrieval from the dual-Doppler wind fields for two storms, the 29-30 May 2012 supercell storm and the 21 June 2012 multicell storm, observed during the Deep Convective Clouds and Chemistry experiment. Using these data, we then compare the inferred microphysical and kinematic characteristics of regions in which the Oklahoma Lightning Mapping Array indicated that flashes were initiated in these two very different storms.

Galangin suppresses HepG2 cell proliferation by activating the TGF-β receptor/Smad pathway

International Nuclear Information System (INIS)

Wang, Yajun; Wu, Jun; Lin, Biyun; Li, Xv; Zhang, Haitao; Ding, Hang; Chen, Xiaoyi; Lan, Liubo; Luo, Hui

2014-01-01

Galangin can suppress hepatocellular carcinoma (HCC) cell proliferation. In this study, we demonstrated that galangin induced autophagy by activating the transforming growth factor (TGF)-β receptor/Smad pathway and increased TGF-β receptor I (RI), TGF-βRII, Smad1, Smad2, Smad3 and Smad4 levels but decreased Smad6 and Smad7 levels. Autophagy induced by galangin appears to depend on the TGF-β receptor/Smad signalling pathway because the down-regulation of Smad4 by siRNA or inhibition of TGF-β receptor activation by LY2109761 blocked galangin-induced autophagy. The down-regulation of Beclin1, autophagy-related gene (ATG) 16L, ATG12 and ATG3 restored HepG2 cell proliferation and prevented galangin-induced apoptosis. Our findings indicate a novel mechanism for galangin-induced autophagy via activation of the TGF-β receptor/Smad pathway. The induction of autophagy thus reflects the anti-proliferation effect of galangin on HCC cells

Foundation Flash Cartoon Animation

CERN Document Server

Jones, Tim; Rosson, Allan S

2008-01-01

One of Flash s most common uses is still animation for cartoons, games, advertising etc, and this book takes a fresh look at the topic, breaking it down pre-production, production, and post production, and looking at each section in detail, and covering topics such as storyboarding, character libraries and camera mechanics like no Flash book has before. The book is written by members of the Emmy award winning ANIMAX team, who have created work for clients such as Disney, AOL, Fox, WWE, ESPN, and Sesame workshop. This book is an opportunity for them to share their secrets, and is written to sui

Weak positive cloud-to-ground flashes in Northeastern Colorado

Science.gov (United States)

Lopez, Raul E.; Maier, Michael W.; Garcia-Miguel, Juan A.; Holle, Ronald L.

1991-01-01

The frequency distributions of the peak magnetic field associated with the first detected return stroke of positive and negative cloud-to-ground (CG) flashes were studied using lightning data from northeastern Colorado. These data were obtained during 1985 with a medium-to-high gain network of three direction finders (DF's). The median signal strength of positive flashes was almost two times that of the negatives for flashes within 300 km of the DF's, which have an inherent detection-threshold bias that tends to discriminate against weak signals. This bias increases with range, and affects the detection of positive and negative flashes in different ways, because of the differing character of their distributions. Positive flashes appear to have a large percentage of signals clustered around very weak values that are lost to the medium-to-high gain Colorado Detection System very quickly with increasing range. The resulting median for positive signals could thus appear to be much larger than the median for negative signals, which are more clustered around intermediate values. When only flashes very close to the DF's are considered, however, the two distributions have almost identical medians. The large percentage of weak positive signals detected close to the DF's has not been explored previously. They have been suggested to come from intracloud discharges and thus are improperly classified as CG flashes. Evidence in hand, points to their being real positive, albeit weak CG flashes. Whether or not they are real positive ground flashes, it is important to be aware of their presence in data from magnetic DF networks.

Flash hydropyrolysis of bituminous coal . III. Research on flash hydropyrolysis tar

Energy Technology Data Exchange (ETDEWEB)

Dong, M.; Zhu, Z.; He, Y.; Ding, N.; Tang, L. [East China University of Science and Technology, Shanghai (China)

2000-02-01

Tar sample obtained by flash hydropyrolysis (FHP) from Dongshen coal at high pressure entrained reactor was investigated. An effect of flash hydropyrolysis temperature on the main components in tar was studied and the quality of the tar was compared with high temperature coke oven tar. The results showed that: the yields of liquid hydrocarbon in FHP tar were more than 15%, which is twofold of that in coke oven tar; the FHP tar has high oil fraction and low pitch; high phenol components and pure condensed polycyclic aromatic hydrocarbon, and low aliphatic hydrocarbon. The components of the FHP tar were simpler than that of high temperature coke oven tar. Therefore, FHP has improved the quantity and quality of tar. 11 refs., 3 figs., 5 tabs.

The framework of a UAS-aided flash flood modeling system for coastal regions

Science.gov (United States)

Zhang, H.; Xu, H.

2016-02-01

Flash floods cause severe economic damage and are one of the leading causes of fatalities connected with natural disasters in the Gulf Coast region. Current flash flood modeling systems rely on empirical hydrological models driven by precipitation estimates only. Although precipitation is the driving factor for flash floods, soil moisture, urban drainage system and impervious surface have been recognized to have significant impacts on the development of flash floods. We propose a new flash flooding modeling system that integrates 3-D hydrological simulation with satellite and multi-UAS observations. It will have three advantages over existing modeling systems. First, it will incorporate 1-km soil moisture data through integrating satellite images from European SMOS mission and NASA's SMAP mission. The utilization of high-resolution satellite images will provide essential information to determine antecedent soil moisture condition, which is an essential control on flood generation. Second, this system is able to adjust flood forecasting based on real-time inundation information collected by multi-UAS. A group of UAS will be deployed during storm events to capture the changing extent of flooded areas and water depth at multiple critical locations simultaneously. Such information will be transmitted to a hydrological model to validate and improve flood simulation. Third, the backbone of this system is a state-of-the-art 3-D hydrological model that assimilates the hydrological information from satellites and multi-UAS. The model is able to address surface water-groundwater interactions and reflect the effects of various infrastructures. Using Web-GIS technologies, the modeling results will be available online as interactive flood maps accessible to the public. To support the development and verification of this modeling system, surface and subsurface hydrological observations will be conducted in a number of small watersheds in the Coastal Bend region. We envision this

Apoptotic role of TGF-β mediated by Smad4 mitochondria translocation and cytochrome c oxidase subunit II interaction.

Science.gov (United States)

Pang, Lijuan; Qiu, Tao; Cao, Xu; Wan, Mei

2011-07-01

Smad4, originally isolated from the human chromosome 18q21, is a key factor in transducing the signals of the TGF-β superfamily of growth hormones and plays a pivotal role in mediating antimitogenic and proapoptotic effects of TGF-β, but the mechanisms by which Smad4 induces apoptosis are elusive. Here we report that Smad4 directly translocates to the mitochondria of apoptotic cells. Smad4 gene silencing by siRNA inhibits TGF-β-induced apoptosis in Hep3B cells and UV-induced apoptosis in PANC-1 cells. Cell fractionation assays demonstrated that a fraction of Smad4 translocates to mitochondria after long time TGF-β treatment or UV exposure, during which the cells were under apoptosis. Smad4 mitochondria translocation during apoptosis was also confirmed by fluorescence observation of Smad4 colocalization with MitoTracker Red. We searched for mitochondria proteins that have physical interactions with Smad4 using yeast two-hybrid screening approach. DNA sequence analysis identified 34 positive clones, five of which encoded subunits in mitochondria complex IV, i.e., one clone encoded cytochrome c oxidase COXII, three clones encoded COXIII and one clone encoded COXVb. Strong interaction between Smad4 with COXII, an important apoptosis regulator, was verified in yeast by β-gal activity assays and in mammalian cells by immunoprecipitation assays. Further, mitochondrial portion of cells was isolated and the interaction between COXII and Smad4 in mitochondria upon TGF-β treatment or UV exposure was confirmed. Importantly, targeting Smad4 to mitochondria using import leader fusions enhanced TGF-β-induced apoptosis. Collectively, the results suggest that Smad4 promote apoptosis of the cells through its mitochondrial translocation and association with mitochondria protein COXII. Copyright © 2011 Elsevier Inc. All rights reserved.

Intra-bunch-train transverse dynamics in the superconducting accelerators FLASH and European XFEL

Energy Technology Data Exchange (ETDEWEB)

Hellert, Thorsten

2017-11-15

FLASH and the European XFEL are linear accelerator driven SASE-FELs, operating in a pulsed mode with long bunch-trains. Multi-bunch FEL operation requires longitudinal and transverse stability within the bunch-train. The purpose of this work is to investigate the intra-bunch-train transverse dynamics at FLASH and XFEL. Key relationships of superconducting RF cavity operation, their misalignments and the resulting impact on the intra-bunch-train trajectory variation are described. In this thesis a numerical model is developed and simulations for different accelerating sections at FLASH and XFEL are performed. With the current operational setup significant intra-bunch-train trajectory variation must be considered, hence approaches for their reduction are discussed. The theoretical studies are compared to experimental results at FLASH. The observed trajectory variation during multi-bunch user runs is analyzed and related to causal intra-bunch-train variations of the RF and the following impact on the multi-bunch SASSE performance. Furthermore, HOM-based cavity misalignment measurements are performed and the deduction of misalignments from multi-bunch data is considered.

Intra-bunch-train transverse dynamics in the superconducting accelerators FLASH and European XFEL

International Nuclear Information System (INIS)

Hellert, Thorsten

2017-11-01

FLASH and the European XFEL are linear accelerator driven SASE-FELs, operating in a pulsed mode with long bunch-trains. Multi-bunch FEL operation requires longitudinal and transverse stability within the bunch-train. The purpose of this work is to investigate the intra-bunch-train transverse dynamics at FLASH and XFEL. Key relationships of superconducting RF cavity operation, their misalignments and the resulting impact on the intra-bunch-train trajectory variation are described. In this thesis a numerical model is developed and simulations for different accelerating sections at FLASH and XFEL are performed. With the current operational setup significant intra-bunch-train trajectory variation must be considered, hence approaches for their reduction are discussed. The theoretical studies are compared to experimental results at FLASH. The observed trajectory variation during multi-bunch user runs is analyzed and related to causal intra-bunch-train variations of the RF and the following impact on the multi-bunch SASSE performance. Furthermore, HOM-based cavity misalignment measurements are performed and the deduction of misalignments from multi-bunch data is considered.

Improving Flash Flood Prediction in Multiple Environments

Science.gov (United States)

Broxton, P. D.; Troch, P. A.; Schaffner, M.; Unkrich, C.; Goodrich, D.; Wagener, T.; Yatheendradas, S.

2009-12-01

Flash flooding is a major concern in many fast responding headwater catchments . There are many efforts to model and to predict these flood events, though it is not currently possible to adequately predict the nature of flash flood events with a single model, and furthermore, many of these efforts do not even consider snow, which can, by itself, or in combination with rainfall events, cause destructive floods. The current research is aimed at broadening the applicability of flash flood modeling. Specifically, we will take a state of the art flash flood model that is designed to work with warm season precipitation in arid environments, the KINematic runoff and EROSion model (KINEROS2), and combine it with a continuous subsurface flow model and an energy balance snow model. This should improve its predictive capacity in humid environments where lateral subsurface flow significantly contributes to streamflow, and it will make possible the prediction of flooding events that involve rain-on-snow or rapid snowmelt. By modeling changes in the hydrologic state of a catchment before a flood begins, we can also better understand the factors or combination of factors that are necessary to produce large floods. Broadening the applicability of an already state of the art flash flood model, such as KINEROS2, is logical because flash floods can occur in all types of environments, and it may lead to better predictions, which are necessary to preserve life and property.

Deficiency of thioredoxin binding protein-2 (TBP-2 enhances TGF-β signaling and promotes epithelial to mesenchymal transition.

Directory of Open Access Journals (Sweden)

So Masaki

Full Text Available Transforming growth factor beta (TGF-β has critical roles in regulating cell growth, differentiation, apoptosis, invasion and epithelial-mesenchymal transition (EMT of various cancer cells. TGF-β-induced EMT is an important step during carcinoma progression to invasion state. Thioredoxin binding protein-2 (TBP-2, also called Txnip or VDUP1 is downregulated in various types of human cancer, and its deficiency results in the earlier onset of cancer. However, it remains unclear how TBP-2 suppresses the invasion and metastasis of cancer.In this study, we demonstrated that TBP-2 deficiency increases the transcriptional activity in response to TGF-β and also enhances TGF-β-induced Smad2 phosphorylation levels. Knockdown of TBP-2 augmented the TGF-β-responsive expression of Snail and Slug, transcriptional factors related to TGF-β-mediated induction of EMT, and promoted TGF-β-induced spindle-like morphology consistent with the depletion of E-Cadherin in A549 cells.Our results indicate that TBP-2 deficiency enhances TGF-β signaling and promotes TGF-β-induced EMT. The control of TGF-β-induced EMT is critical for the inhibition of the invasion and metastasis. Thus TBP-2, as a novel regulatory molecule of TGF-β signaling, is likely to be a prognostic indicator or a potential therapeutic target for preventing tumor progression.

BAG3 regulates ECM accumulation in renal proximal tubular cells induced by TGF-β1.

Science.gov (United States)

Du, Feng; Li, Si; Wang, Tian; Zhang, Hai-Yan; Li, De-Tian; Du, Zhen-Xian; Wang, Hua-Qin; Wang, Yan-Qiu

2015-01-01

Previously we have demonstrated that Bcl-2-associated athanogene 3 (BAG3) is increased in renal fibrosis using a rat unilateral ureteral obstruction model. The current study investigated the role of BAG3 in renal fibrosis using transforming growth factor (TGF)-β1-treated human proximal tubular epithelial (HK-2) cells. An upregulation of BAG3 in vitro models was observed, which correlated with the increased synthesis of extracellular matrix (ECM) proteins and expression of tissue-type plasminogen activator inhibitor (PAI)-1. Blockade of BAG3 induction by shorting hairpin RNA suppressed the expression of ECM proteins but had no effect on PAI-1 expression induced by TGF-β1. Forced overexpression of BAG3 selectively increased collagens. TGF-β1-induced BAG3 expression in HK-2 cells was attenuated by ERK1/2 and JNK MAPK inhibitors. In addition, forced BAG3 overexpression blocked attenuation of collagens expression by ERK1/2 and JNK inhibitors. These data suggest that ERK1/2 and JNK signaling events are involved in modulating the expression of BAG3, which would ultimately contribute to renal fibrosis by enhancing the synthesis and deposition of ECM proteins.

Immunohistochemical expression of TGF-β1 and MMP-9 in periapical lesions

Directory of Open Access Journals (Sweden)

Pâmella Recco ÁLVARES

2017-07-01

Full Text Available Abstract The objective of this study was to evaluate the expression of matrix metalloproteinase 9 (MMP-9 and transforming growth factor beta (TGF-β1 in periapical lesion samples correlated with the intensity of the inflammatory infiltrate and thickness of the epithelial lining. Forty-five cases of periapical lesions (23 periapical granulomas and 22 radicular cysts were subjected to morphological and immunohistochemical analyses using anti-MMP-9 and anti-TGF-β1 antibodies. The data were analyzed using the following tests: non-parametric Mann-Whitney, chi-square, Fisher’s exact test and Spearman’s correlation test (P<0.05. Analysis of inflammatory infiltrate revealed that 78% of periapical granulomas presented infiltrate grade III, in contrast with 32% of radicular cysts (P<0.001. Morphological evaluation of the epithelial thickness in radicular cysts revealed the presence of atrophic epithelium in 86% of the cysts. The immunostaining of MMP-9 was score 2 in 67% of the granulomas and 77% of the cysts. Both lesions were predominantly score 1 for TGF-β1. Significant differences were confirmed between the expression scores of TGF-β1 and MMP-9 in periapical granulomas (p = 0.004 and in radicular cysts (p < 0.001. Expression of TGF-β1 was different for periapical granulomas and radicular cysts. This immunoregulatory cytokine seems more representative in asymptomatic lesions. The extracellular matrix remodeling process dependent on MMP-9 seems to be similar for both periapical granulomas and radicular cysts. TGF-β1 and MMP-9 may play an important role in the maintenance of periapical lesions.

Osteoclast TGF-β Receptor Signaling Induces Wnt1 Secretion and Couples Bone Resorption to Bone Formation

Science.gov (United States)

Weivoda, Megan M; Ruan, Ming; Pederson, Larry; Hachfeld, Christine; Davey, Rachel A; Zajac, Jeffrey D; Westendorf, Jennifer J; Khosla, Sundeep; Oursler, Merry Jo

2016-01-01

Osteoblast-mediated bone formation is coupled to osteoclast-mediated bone resorption. These processes become uncoupled with age, leading to increased risk for debilitating fractures. Therefore, understanding how osteoblasts are recruited to sites of resorption is vital to treating age-related bone loss. Osteoclasts release and activate TGF-β from the bone matrix. Here we show that osteoclastspecific inhibition of TGF-β receptor signaling in mice results in osteopenia due to reduced osteoblast numbers with no significant impact on osteoclast numbers or activity. TGF-β induced osteoclast expression of Wnt1, a protein crucial to normal bone formation, and this response was blocked by impaired TGF-β receptor signaling. Osteoclasts in aged murine bones had lower TGF-β signaling and Wnt1 expression in vivo. Ex vivo stimulation of osteoclasts derived from young or old mouse bone marrow macrophages showed no difference in TGF-β–induced Wnt1 expression. However, young osteoclasts expressed reduced Wnt1 when cultured on aged mouse bone chips compared to young mouse bone chips, consistent with decreased skeletal TGF-β availability with age. Therefore, osteoclast responses to TGF-β are essential for coupling bone resorption to bone formation, and modulating this pathway may provide opportunities to treat age-related bone loss. PMID:26108893

Flash flood modelling for ungauged catchments

Science.gov (United States)

Garambois, P.-A.; Roux, H.; Larnier, K.; Dartus, D.

2012-04-01

Flash flood is a very intense and quick hydrologic response of a catchment to rainfall. This phenomenon has a high spatial-temporal variability as its generating storm, often hitting small catchments (few km2). Data collected by (Gaume et al. 2009) about 500 flash floods over the last 50 years showed that they could occur everywhere in Europe and more often in the Mediterranean regions, Alpine regions and continental Europe. Given the small spatial-temporal scales and high variability of flash floods, their prediction remains a hard exercise as the necessary data are often scarce. Flash flood prediction on ungauged catchments is one of the challenges of hydrological modelling as defined by (Sivapalan et al. 2003). Several studies have been headed up with the MARINE model (Modélisation de l'Anticipation du Ruissellement et des Inondations pour des évèNements Extrêmes) for the Gard region (France), (Roux et al. 2011), (Castaings et al. 2009). This physically based spatially distributed rainfall runoff model is dedicated to flash flood prediction. The study aims at finding a methodology for flash flood prediction at ungauged locations in the Cévennes-Vivarais region in particular. The regionalization method is based on multiple calibrations on gauged catchments in order to extract model structures (model + parameter values) for each catchment. Several mathematical methods (multiple regressions, transfer functions, krigging…) will then be tested to calculate a regional parameter set. The study also investigates the usability of additional hydrologic indices at different time scales to constrain model predictions from parameters obtained using these indices, and this independently of the model considered. These hydrologic indices gather information on hydrograph shape or catchment dynamic for instance. Results explaining global catchments behaviour are expected that way. The spatial-temporal variability of storms is also described through indices and linked with

Bronchoconstriction Induces TGF-β Release and Airway Remodelling in Guinea Pig Lung Slices.

Directory of Open Access Journals (Sweden)

Tjitske A Oenema

Full Text Available Airway remodelling, including smooth muscle remodelling, is a primary cause of airflow limitation in asthma. Recent evidence links bronchoconstriction to airway remodelling in asthma. The mechanisms involved are poorly understood. A possible player is the multifunctional cytokine TGF-β, which plays an important role in airway remodelling. Guinea pig lung slices were used as an in vitro model to investigate mechanisms involved in bronchoconstriction-induced airway remodelling. To address this aim, mechanical effects of bronchoconstricting stimuli on contractile protein expression and TGF-β release were investigated. Lung slices were viable for at least 48 h. Both methacholine and TGF-β1 augmented the expression of contractile proteins (sm-α-actin, sm-myosin, calponin after 48 h. Confocal fluorescence microscopy showed that increased sm-myosin expression was enhanced in the peripheral airways and the central airways. Mechanistic studies demonstrated that methacholine-induced bronchoconstriction mediated the release of biologically active TGF-β, which caused the increased contractile protein expression, as inhibition of actin polymerization (latrunculin A or TGF-β receptor kinase (SB431542 prevented the methacholine effects, whereas other bronchoconstricting agents (histamine and KCl mimicked the effects of methacholine. Collectively, bronchoconstriction promotes the release of TGF-β, which induces airway smooth muscle remodelling. This study shows that lung slices are a useful in vitro model to study mechanisms involved in airway remodelling.

Flashing light in microalgae biotechnology.

Science.gov (United States)

Abu-Ghosh, Said; Fixler, Dror; Dubinsky, Zvy; Iluz, David

2016-03-01

Flashing light can enhance photosynthesis and improve the quality and quantity of microalgal biomass, as it can increase the products of interest by magnitudes. Therefore, the integration of flashing light effect into microalgal cultivation systems should be considered. However, microalgae require a balanced mix of the light/dark cycle for higher growth rates, and respond to light intensity differently according to the pigments acquired or lost during the growth. This review highlights recently published results on flashing light effect on microalgae and its applications in biotechnology, as well as the recently developed bioreactors designed to fulfill this effect. It also discusses how this knowledge can be applied in selecting the optimal light frequencies and intensities with specific technical properties for increasing biomass production and/or the yield of the chemicals of interest by microalgae belonging to different genera. Copyright © 2015 Elsevier Ltd. All rights reserved.

An unusual characteristic “flower-like” pattern: flash suppressor burns

OpenAIRE

Gurcan, Altun

2012-01-01

The case on contact shots from firearms with a flash suppressor is rare. When a rifle fitted with a flash suppressor is fired, the emerging soot-laden gas in the barrel escapes from the slits of the flash suppressor. If the shot is contact or near contact, the flash suppressor will produce a characteristic “flower-like” pattern of seared, blackened zones around the entrance. This paper presents the injury pattern of the flash suppressor in a 29-year-old man who committed suicide with a G3 aut...

An unusual characteristic “flower-like” pattern: flash suppressor burns

Science.gov (United States)

Gurcan, Altun

2012-01-01

The case on contact shots from firearms with a flash suppressor is rare. When a rifle fitted with a flash suppressor is fired, the emerging soot-laden gas in the barrel escapes from the slits of the flash suppressor. If the shot is contact or near contact, the flash suppressor will produce a characteristic “flower-like” pattern of seared, blackened zones around the entrance. This paper presents the injury pattern of the flash suppressor in a 29-year-old man who committed suicide with a G3 automatic infantry rifle. PMID:23935280

Histone acetyltransferase TGF-1 regulates Trichoderma atroviride secondary metabolism and mycoparasitism.

Science.gov (United States)

Gómez-Rodríguez, Elida Yazmín; Uresti-Rivera, Edith Elena; Patrón-Soberano, Olga Araceli; Islas-Osuna, María Auxiliadora; Flores-Martínez, Alberto; Riego-Ruiz, Lina; Rosales-Saavedra, María Teresa; Casas-Flores, Sergio

2018-01-01

Some filamentous fungi of the Trichoderma genus are used as biocontrol agents against airborne and soilborne phytopathogens. The proposed mechanism by which Trichoderma spp. antagonizes phytopathogens is through the release of lytic enzymes, antimicrobial compounds, mycoparasitism, and the induction of systemic disease-resistance in plants. Here we analyzed the role of TGF-1 (Trichoderma Gcn Five-1), a histone acetyltransferase of Trichoderma atroviride, in mycoparasitism and antibiosis against the phytopathogen Rhizoctonia solani. Trichostatin A (TSA), a histone deacetylase inhibitor that promotes histone acetylation, slightly affected T. atroviride and R. solani growth, but not the growth of the mycoparasite over R. solani. Application of TSA to the liquid medium induced synthesis of antimicrobial compounds. Expression analysis of the mycoparasitism-related genes ech-42 and prb-1, which encode an endochitinase and a proteinase, as well as the secondary metabolism-related genes pbs-1 and tps-1, which encode a peptaibol synthetase and a terpene synthase, respectively, showed that they were regulated by TSA. A T. atroviride strain harboring a deletion of tgf-1 gene showed slow growth, thinner and less branched hyphae than the wild-type strain, whereas its ability to coil around the R. solani hyphae was not affected. Δtgf-1 presented a diminished capacity to grow over R. solani, but the ability of its mycelium -free culture filtrates (MFCF) to inhibit the phytopathogen growth was enhanced. Intriguingly, addition of TSA to the culture medium reverted the enhanced inhibition growth of Δtgf-1 MFCF on R. solani at levels compared to the wild-type MFCF grown in medium amended with TSA. The presence of R. solani mycelium in the culture medium induced similar proteinase activity in a Δtgf-1 compared to the wild-type, whereas the chitinolytic activity was higher in a Δtgf-1 mutant in the absence of R. solani, compared to the parental strain. Expression of mycoparasitism

Histone acetyltransferase TGF-1 regulates Trichoderma atroviride secondary metabolism and mycoparasitism.

Directory of Open Access Journals (Sweden)

Elida Yazmín Gómez-Rodríguez

Full Text Available Some filamentous fungi of the Trichoderma genus are used as biocontrol agents against airborne and soilborne phytopathogens. The proposed mechanism by which Trichoderma spp. antagonizes phytopathogens is through the release of lytic enzymes, antimicrobial compounds, mycoparasitism, and the induction of systemic disease-resistance in plants. Here we analyzed the role of TGF-1 (Trichoderma Gcn Five-1, a histone acetyltransferase of Trichoderma atroviride, in mycoparasitism and antibiosis against the phytopathogen Rhizoctonia solani. Trichostatin A (TSA, a histone deacetylase inhibitor that promotes histone acetylation, slightly affected T. atroviride and R. solani growth, but not the growth of the mycoparasite over R. solani. Application of TSA to the liquid medium induced synthesis of antimicrobial compounds. Expression analysis of the mycoparasitism-related genes ech-42 and prb-1, which encode an endochitinase and a proteinase, as well as the secondary metabolism-related genes pbs-1 and tps-1, which encode a peptaibol synthetase and a terpene synthase, respectively, showed that they were regulated by TSA. A T. atroviride strain harboring a deletion of tgf-1 gene showed slow growth, thinner and less branched hyphae than the wild-type strain, whereas its ability to coil around the R. solani hyphae was not affected. Δtgf-1 presented a diminished capacity to grow over R. solani, but the ability of its mycelium -free culture filtrates (MFCF to inhibit the phytopathogen growth was enhanced. Intriguingly, addition of TSA to the culture medium reverted the enhanced inhibition growth of Δtgf-1 MFCF on R. solani at levels compared to the wild-type MFCF grown in medium amended with TSA. The presence of R. solani mycelium in the culture medium induced similar proteinase activity in a Δtgf-1 compared to the wild-type, whereas the chitinolytic activity was higher in a Δtgf-1 mutant in the absence of R. solani, compared to the parental strain. Expression

uFLIP: Understanding the Energy Consumption of Flash Devices

DEFF Research Database (Denmark)

Bjørling, Matias; Bonnet, Philippe; Bouganim, Luc

2010-01-01

Understanding the energy consumption of flash devices is important for two reasons. First, energy is emerging as a key metric for data management systems. It is thus important to understand how we can reason about the energy consumption of flash devices beyond their approximate aggregate...... consumption (low power consumption in idle mode, average Watt consumption from the data sheets). Second, when measured at a sufficiently fine granularity, the energy consumption of a given device might complement the performance characteristics derived from its response time profile. Indeed, background work...... which is not directly observable with a response time profile appears clearly when energy is used as a metric. In this paper, we discuss the results from the {uFLIP} benchmark applied to four different {SSD} devices using both response time and energy as metric....

Flash propagation and inferred charge structure relative to radar-observed ice alignment signatures in a small Florida mesoscale convective system

Science.gov (United States)

Biggerstaff, Michael I.; Zounes, Zackery; Addison Alford, A.; Carrie, Gordon D.; Pilkey, John T.; Uman, Martin A.; Jordan, Douglas M.

2017-08-01

A series of vertical cross sections taken through a small mesoscale convective system observed over Florida by the dual-polarimetric SMART radar were combined with VHF radiation source locations from a lightning mapping array (LMA) to examine the lightning channel propagation paths relative to the radar-observed ice alignment signatures associated with regions of negative specific differential phase (KDP). Additionally, charge layers inferred from analysis of LMA sources were related to the ice alignment signature. It was found that intracloud flashes initiated near the upper zero-KDP boundary surrounding the negative KDP region. The zero-KDP boundary also delineated the propagation path of the lightning channel with the negative leaders following the upper boundary and positive leaders following the lower boundary. Very few LMA sources were found in the negative KDP region. We conclude that rapid dual-polarimetric radar observations can diagnose strong electric fields and may help identify surrounding regions of charge.

Celastrol inhibits TGF-β1-induced epithelial–mesenchymal transition by inhibiting Snail and regulating E-cadherin expression

Energy Technology Data Exchange (ETDEWEB)

Kang, Hyereen; Lee, Minjae [Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul 138-736 (Korea, Republic of); Jang, Sung-Wuk, E-mail: swjang@amc.seoul.kr [Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul 138-736 (Korea, Republic of); Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul 138-736 (Korea, Republic of)

2013-08-09

Highlights: •We investigated the effects of celastrol on TGF-β1-induced EMT in epithelial cells. •Celastrol regulates TGF-β1-induced morphological changes and E-cadherin expression. •Celastrol inhibits TGF-β1-induced Snail expression. •Celastrol strongly suppresses TGF-β1-induced invasion in MDCK and A549 cells. -- Abstract: The epithelial–mesenchymal transition (EMT) is a pivotal event in the invasive and metastatic potentials of cancer progression. Celastrol inhibits the proliferation of a variety of tumor cells including leukemia, glioma, prostate, and breast cancer; however, the possible role of celastrol in the EMT is unclear. We investigated the effect of celastrol on the EMT. Transforming growth factor-beta 1 (TGF-β1) induced EMT-like morphologic changes and upregulation of Snail expression. The downregulation of E-cadherin expression and upregulation of Snail in Madin–Darby Canine Kidney (MDCK) and A549 cell lines show that TGF-β1-mediated the EMT in epithelial cells; however, celastrol markedly inhibited TGF-β1-induced morphologic changes, Snail upregulation, and E-cadherin expression. Migration and invasion assays revealed that celastrol completely inhibited TGF-β1-mediated cellular migration in both cell lines. These findings indicate that celastrol downregulates Snail expression, thereby inhibiting TGF-β1-induced EMT in MDCK and A549 cells. Thus, our findings provide new evidence that celastrol suppresses lung cancer invasion and migration by inhibiting TGF-β1-induced EMT.

Replacing HDDs with Solid-State Flash Disks in PXIbus-Based Systems

International Nuclear Information System (INIS)

Zhao, Z W; Zeng, L

2006-01-01

New security features, constantly decreasing prices, solid-state Flash disks are becoming a popular alternative for replacing failure-prone mechanical Hard Disk Drives (HDDs) in PXIbus-based military systems. The key component in high-capacity solid-state Flash disks is NAND Flash, but with a specification that shows only 100,000-300,000 write/erase cycles, engineers may be concerned that the lifetime of Flash disks cannot meet their application requirements. With the right Flash management, Flash disks are able to provide the reliability and endurance that military applications need

B lymphocytes confer immune tolerance via cell surface GARP-TGF-β complex.

Science.gov (United States)

Wallace, Caroline H; Wu, Bill X; Salem, Mohammad; Ansa-Addo, Ephraim A; Metelli, Alessandra; Sun, Shaoli; Gilkeson, Gary; Shlomchik, Mark J; Liu, Bei; Li, Zihai

2018-04-05

GARP, a cell surface docking receptor for binding and activating latent TGF-β, is highly expressed by platelets and activated Tregs. While GARP is implicated in immune invasion in cancer, the roles of the GARP-TGF-β axis in systemic autoimmune diseases are unknown. Although B cells do not express GARP at baseline, we found that the GARP-TGF-β complex is induced on activated human and mouse B cells by ligands for multiple TLRs, including TLR4, TLR7, and TLR9. GARP overexpression on B cells inhibited their proliferation, induced IgA class-switching, and dampened T cell-independent antibody production. In contrast, B cell-specific deletion of GARP-encoding gene Lrrc32 in mice led to development of systemic autoimmune diseases spontaneously as well as worsening of pristane-induced lupus-like disease. Canonical TGF-β signaling more readily upregulates GARP in Peyer patch B cells than in splenic B cells. Furthermore, we demonstrated that B cells are required for the induction of oral tolerance of T cell-dependent antigens via GARP. Our studies reveal for the first time to our knowledge that cell surface GARP-TGF-β is an important checkpoint for regulating B cell peripheral tolerance, highlighting a mechanism of autoimmune disease pathogenesis.

Cardioprotection against Heart Failure by Shenfu Injection via TGF-β/Smads Signaling Pathway

Directory of Open Access Journals (Sweden)

Jingyu Ni

2017-01-01

Full Text Available Objective. To explore the potential cardioprotective mechanism of Shenfu injection (SFI against heart failure (HF by attenuating myocardial fibrosis and cardiac remodeling. Methods and Results. Four weeks after myocardial infarction (MI, adult male Sprague Dawley rats were randomized for 4-week treatment with Valsartan, SFI, or vehicle. Echocardiography and hemodynamics were applied to evaluate cardiac functions. Myocardia of coronary artery ligated (CAD rats were observed to investigate changes in cardiac structure and function. Our findings suggest that treatment with SFI could inhibit progression of myocardial fibrosis and attenuate cardiac remodeling. In addition, SFI decreased expression of Smad2 and Smad3, while increasing the expression of Smad7 through regulation of TGF-β/Smads signaling pathway. Conclusion. Treatment with SFI in Sprague Dawley rats improves ventricular structure and function and reduces cardiac fibrosis by ameliorating TGF-β/Smads signaling pathway after ventricular remodeling.

Cardiac autonomic function and hot flashes among perimenopausal and postmenopausal women.

Science.gov (United States)

Gibson, Carolyn J; Mendes, Wendy Berry; Schembri, Michael; Grady, Deborah; Huang, Alison J

2017-07-01

Abnormalities in autonomic function are posited to play a pathophysiologic role in menopausal hot flashes. We examined relationships between resting cardiac autonomic activity and hot flashes in perimenopausal and postmenopausal women. Autonomic function was assessed at baseline and 12 weeks among perimenopausal and postmenopausal women (n = 121, mean age 53 years) in a randomized trial of slow-paced respiration for hot flashes. Pre-ejection period (PEP), a marker of sympathetic activation, was measured with impedance cardiography. Respiratory sinus arrhythmia (RSA), a marker of parasympathetic activation, was measured with electrocardiography. Participants self-reported hot flash frequency and severity in 7-day symptom diaries. Analysis of covariance models were used to relate autonomic function and hot flash frequency and severity at baseline, and to relate changes in autonomic function to changes in hot flash frequency and severity over 12 weeks, adjusting for age, body mass index, and intervention assignment. PEP was not associated with hot flash frequency or severity at baseline or over 12 weeks (P > 0.05 for all). In contrast, there was a trend toward greater frequency of moderate-to-severe hot flashes with higher RSA at baseline (β = 0.43, P = 0.06), and a positive association between change in RSA and change in frequency of moderate-to-severe hot flashes over 12 weeks (β = 0.63, P = 0.04). Among perimenopausal and postmenopausal women with hot flashes, variations in hot flash frequency and severity were not explained by variations in resting sympathetic activation. Greater parasympathetic activation was associated with more frequent moderate-to-severe hot flashes, which may reflect increased sensitivity to perceiving hot flashes.

The Essential Guide to 3D in Flash

CERN Document Server

Olsson, Ronald A

2010-01-01

If you are an ActionScript developer or designer and you would like to work with 3D in Flash, this book is for you. You will learn the core Flash 3D concepts, using the open source Away3D engine as a primary tool. Once you have mastered these skills, you will be able to realize the possibilities that the available Flash 3D engines, languages, and technologies have to offer you with Flash and 3D.* Describes 3D concepts in theory and their implementation using Away3D* Dives right in to show readers how to quickly create an interactive, animated 3D scene, and builds on that experience throughout

Maintaining the immunological balance in parasitic infections: a role for TGF-ß?

DEFF Research Database (Denmark)

Omer, F M; Kurtzhals, J A; Riley, E M

2000-01-01

on the one hand and prevention of immune-mediated pathology on the other. In this article, Fakhereldin Omer, Jørgen Kurtzhals and Eleanor Riley review the immunoregulatory properties of TGF-beta in the context of parasitic infections. Data from murine malaria infections suggest that TGF-beta modifies...

Osteocyte-Intrinsic TGF-β Signaling Regulates Bone Quality through Perilacunar/Canalicular Remodeling

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Neha S. Dole

2017-11-01

Full Text Available Poor bone quality contributes to bone fragility in diabetes, aging, and osteogenesis imperfecta. However, the mechanisms controlling bone quality are not well understood, contributing to the current lack of strategies to diagnose or treat bone quality deficits. Transforming growth factor beta (TGF-β signaling is a crucial mechanism known to regulate the material quality of bone, but its cellular target in this regulation is unknown. Studies showing that osteocytes directly remodel their perilacunar/canalicular matrix led us to hypothesize that TGF-β controls bone quality through perilacunar/canalicular remodeling (PLR. Using inhibitors and mice with an osteocyte-intrinsic defect in TGF-β signaling (TβRIIocy−/−, we show that TGF-β regulates PLR in a cell-intrinsic manner to control bone quality. Altogether, this study emphasizes that osteocytes are key in executing the biological control of bone quality through PLR, thereby highlighting the fundamental role of osteocyte-mediated PLR in bone homeostasis and fragility.

Osteocyte-Intrinsic TGF-β Signaling Regulates Bone Quality through Perilacunar/Canalicular Remodeling.

Science.gov (United States)

Dole, Neha S; Mazur, Courtney M; Acevedo, Claire; Lopez, Justin P; Monteiro, David A; Fowler, Tristan W; Gludovatz, Bernd; Walsh, Flynn; Regan, Jenna N; Messina, Sara; Evans, Daniel S; Lang, Thomas F; Zhang, Bin; Ritchie, Robert O; Mohammad, Khalid S; Alliston, Tamara

2017-11-28

Poor bone quality contributes to bone fragility in diabetes, aging, and osteogenesis imperfecta. However, the mechanisms controlling bone quality are not well understood, contributing to the current lack of strategies to diagnose or treat bone quality deficits. Transforming growth factor beta (TGF-β) signaling is a crucial mechanism known to regulate the material quality of bone, but its cellular target in this regulation is unknown. Studies showing that osteocytes directly remodel their perilacunar/canalicular matrix led us to hypothesize that TGF-β controls bone quality through perilacunar/canalicular remodeling (PLR). Using inhibitors and mice with an osteocyte-intrinsic defect in TGF-β signaling (TβRII ocy-/- ), we show that TGF-β regulates PLR in a cell-intrinsic manner to control bone quality. Altogether, this study emphasizes that osteocytes are key in executing the biological control of bone quality through PLR, thereby highlighting the fundamental role of osteocyte-mediated PLR in bone homeostasis and fragility. Published by Elsevier Inc.

TGF-β2 inhibits AKT activation and FGF-2-induced corneal endothelial cell proliferation

International Nuclear Information System (INIS)

Lu Jiawei; Lu Zhenyu; Reinach, Peter

2006-01-01

The corneal endothelial cells form a boundary layer between anterior chamber and cornea. This single cell layer is important to maintain cornea transparency by eliciting net fluid transport into the anterior chamber. Injuries of the corneal endothelial layer in humans lead to corneal swelling and translucence. This hindrance is thought to be due to limited proliferative capacity of the endothelial layer. Fibroblast growth factor 2 (FGF-2) and transforming growth factor-beta 2 (TGF-β2) are both found in aqueous humor, and these two cytokines promote and inhibit cell growth, respectively. The intracellular signaling mechanisms by which TGF-β2 suppresses the mitogenic response to FGF-2, however, remain unclear. We have addressed this question by investigating potential crosstalk between FGF-2-induced and TGF-β2-regulated intracellular signaling events in cultured bovine corneal endothelial (BCE) cells. We found that TGF-β2 and FGF-2 oppositely affect BCE cell proliferation and TGF-β2 can override the stimulating effects of FGF-2 by increasing COX-2 expression in these cells. Consistent with these findings, overexpression of COX-2 significantly reduced FGF-2-induced cell proliferation whereas a COX-2 specific inhibitor NS398 reversed the effect of TGF-β2 on FGF-2-induced cell proliferation. The COX-2 product prostaglandin E2 (PGE-2) blocks FGF-2-induced cell proliferation. Whereas FGF-2 stimulates cell proliferation by activating the AKT pathway, TGF-β2 and PGE-2 both inhibit this pathway. In accordance with the effect of PGE-2, cAMP also inhibits FGF-2-induced AKT activation. These findings suggest that the mitogenic response to FGF-2 in vivo in the corneal endothelial layer may be inhibited by TGF-β2-induced suppression of the PI3-kinase/AKT signaling pathway

Enhanced Dupuytren's disease fibroblast populated collagen lattice contraction is independent of endogenous active TGF-β2

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Howard Jeffrey

2004-11-01

Full Text Available Abstract Background Dupuytren's disease (DD is a debilitating fibro-proliferative disorder of the hand characterized by the appearance of fibrotic lesions (nodules and cords leading to flexion contractures of the fingers and loss of hand function. Although the molecular mechanism of DD is unknown, it has been suggested that transforming growth factor-β2 (TGF-β2 may play an important role in the underlying patho-physiology of the disease. The purpose of this study was to further explore this hypothesis by examining the effects of TGF-β2 on primary cell cultures derived from patient-matched disease and normal palmar fascia tissue using a three-dimensional collagen contraction assay. Methods Fibroblast-populated collagen lattice (FPCL contraction assays using primary cell cultures derived from diseased and control fascia of the same DD patients were studied in response to exogenous TGF-β2 and neutralizing anti-TGF-β2 antibodies. Results Contraction of the FPCLs occurred significantly faster and to a greater extent in disease cells compared to control cells. The addition of TGF-β2 enhanced the rate and degree of collagen contraction in a dose-dependent fashion for both control and diseased cells. Neutralizing anti-TGF-β2 antibodies abolished exogenous TGF-β2 stimulated collagen contraction, but did not inhibit the enhanced basal collagen contraction activity of disease FPCL cultures. Conclusions Although exogenous TGF-β2 stimulated both disease and control FPCL contraction, neutralizing anti-TGF-β2 antibodies did not affect the elevated basal collagen contraction activity of disease FPCLs, suggesting that the differences in the collagen contraction activity of control and disease FPCL cultures are not due to differences in the levels of endogenous TGF-β2 activity.

Shock compression and flash-heating of molecular adsorbates on the picosecond time scale

Science.gov (United States)

Berg, Christopher Michael

An ultrafast nonlinear coherent laser spectroscopy termed broadband multiplex vibrational sum-frequency generation (SFG) with nonresonant suppression was employed to monitor vibrational transitions of molecular adsorbates on metallic substrates during laser-driven shock compression and flash-heating. Adsorbates were in the form of well-ordered self-assembled monolayers (SAMs) and included molecular explosive simulants, such as nitroaromatics, and long chain-length alkanethiols. Based on reflectance measurements of the metallic substrates, femtosecond flash-heating pulses were capable of producing large-amplitude temperature jumps with DeltaT = 500 K. Laser-driven shock compression of SAMs produced pressures up to 2 GPa, where 1 GPa ≈ 1 x 104 atm. Shock pressures were estimated via comparison with frequency shifts observed in the monolayer vibrational transitions during hydrostatic pressure measurements in a SiC anvil cell. Molecular dynamics during flash-heating and shock loading were probed with vibrational SFG spectroscopy with picosecond temporal resolution and sub-nanometer spatial resolution. Flash-heating studies of 4-nitrobenzenethiolate (NBT) on Au provided insight into effects from hot-electron excitation of the molecular adsorbates at early pump-probe delay times. At longer delay times, effects from the excitation of SAM lattice modes and lower-energy NBT vibrations were shown. In addition, flash-heating studies of alkanethiolates demonstrated chain disordering behaviors as well as interface thermal conductances across the Au-SAM junction, which was of specific interest within the context of molecular electronics. Shock compression studies of molecular explosive simulants, such as 4-nitrobenzoate (NBA), demonstrated the proficiency of this technique to observe shock-induced molecular dynamics, in this case orientational dynamics, on the picosecond time scale. Results validated the utilization of these refined shock loading techniques to probe the shock

Professional Flash Mobile Development Creating Android and iPhone Applications

CERN Document Server

Wagner, Richard

2010-01-01

Professional Flash Mobile Development: Creating Android and iPhone ApplicationsEverything Flash developers need to know to create native Android and iPhone appsThis Wrox guide shows Flash developers how to create native applications for Android and iPhone mobile devices using Flash. Packed with practical examples, it shows how to build a variety of apps and integrate them with core mobile services such as Accelerometer, GPS, Photo Library,and more.Offers Flash developers the tools to create apps for the Android and iPhone mobile devicesSho

Inhibitory Effect of NH4Cl Treatment on Renal Tgfß1 Signaling Following Unilateral Ureteral Obstruction

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Martina Feger

2015-09-01

Full Text Available Background/Aims: Consequences of obstructive nephropathy include tissue fibrosis, a major pathophysiological mechanism contributing to development of end-stage renal disease. Transforming growth factor β 1 (Tgfβ1 is involved in the progression of renal fibrosis. According to recent observations, ammonium chloride (NH4Cl prevented phosphate-induced vascular remodeling, effects involving decrease of Tgfβ1 expression and inhibition of Tgfβ1-dependent signaling. The present study, thus, explored whether NH4Cl influences renal Tgfβ1-induced pro-fibrotic signaling in obstructive nephropathy induced by unilateral ureteral obstruction (UUO. Methods: UUO was induced for seven days in C57Bl6 mice with or without additional treatment with NH4Cl (0.28 M in drinking water. Transcript levels were determined by RT-PCR as well as protein abundance by Western blotting, blood pH was determined utilizing a blood gas and chemistry analyser. Results: UUO increased renal mRNA expression of Tgfb1, Tgfβ-activated kinase 1 (Tak1 protein abundance and Smad2 phosphorylation in the nuclear fraction of the obstructed kidney tissues, effects blunted in NH4Cl treated mice as compared to control treated mice. The mRNA levels of the transcription factors nuclear factor of activated T cells 5 (Nfat5 and SRY (sex determining region Y-box 9 (Sox9 as well as of tumor necrosis factor α (Tnfα, interleukin 6 (Il6, plasminogen activator inhibitor 1 (Pai1 and Snai1 were up-regulated in the obstructed kidney tissues following UUO, effects again significantly ameliorated following NH4Cl treatment. Furthermore, the increased protein and mRNA expression of α-smooth muscle actin (α-Sma, fibronectin and collagen type I in the obstructed kidney tissues following UUO were significantly attenuated following NH4Cl treatment. Conclusion: NH4Cl treatment ameliorates Tgfβ1-dependent pro-fibrotic signaling and renal tissue fibrosis markers following obstructive nephropathy.

Activation of TGF-β1-CD147 positive feedback loop in hepatic stellate cells promotes liver fibrosis.

Science.gov (United States)

Li, Hai-Yan; Ju, Di; Zhang, Da-Wei; Li, Hao; Kong, Ling-Min; Guo, Yanhai; Li, Can; Wang, Xi-Long; Chen, Zhi-Nan; Bian, Huijie

2015-11-12

Activation of hepatic stellate cells (HSCs) by transforming growth factor-β1 (TGF-β1) initiates HBV-associated fibrogenesis. The mechanism of TGF-β1 modulating HSC activation is not fully uncovered. We hypothesized a positive feedback signaling loop of TGF-β1-CD147 promoting liver fibrogenesis by activation of HSCs. Human HSC cell line LX-2 and spontaneous liver fibrosis model derived from HBV transgenic mice were used to evaluate the activation of molecules in the signaling loop. Wound healing and cell contraction assay were performed to detect the CD147-overexpressed HSC migration and contraction. The transcriptional regulation of CD147 by TGF-β1/Smad4 was determined using dual-luciferase reporter assay and chromatin immunoprecipitation. We found that a positive reciprocal regulation between TGF-β1 and CD147 mediated HSC activation. CD147 over-expression promoted HSC migration and accelerated TGF-β1-induced cell contraction. Phosphorylation of Smad2 and Smad3 in cooperation with Smad4 mediated the TGF-β1-regulated CD147 expression. Smad4 activated the transcription by direct interaction with CD147 promoter. Meanwhile, CD147 modulated the activated phenotype of HSCs through the ERK1/2 and Sp1 which up-regulated α-SMA, collagen I, and TGF-β1 synthesis. These findings indicate that TGF-β1-CD147 loop plays a key role in regulating the HSC activation and combination of TGF-β receptor inhibitor and anti-CD147 antibody might be promised to reverse fibrogenesis.

A hybrid ferroelectric-flash memory cells

Science.gov (United States)

Park, Jae Hyo; Byun, Chang Woo; Seok, Ki Hwan; Kim, Hyung Yoon; Chae, Hee Jae; Lee, Sol Kyu; Son, Se Wan; Ahn, Donghwan; Joo, Seung Ki

2014-09-01

A ferroelectric-flash (F-flash) memory cells having a metal-ferroelectric-nitride-oxynitride-silicon structure are demonstrated, and the ferroelectric materials were perovskite-dominated Pb(Zr,Ti)O3 (PZT) crystallized by Pt gate electrode. The PZT thin-film as a blocking layer improves electrical and memorial performance where programming and erasing mechanism are different from the metal-ferroelectric-insulator-semiconductor device or the conventional silicon-oxide-nitride-oxide-silicon device. F-flash cells exhibit not only the excellent electrical transistor performance, having 442.7 cm2 V-1 s-1 of field-effect mobility, 190 mV dec-1 of substhreshold slope, and 8 × 105 on/off drain current ratio, but also a high reliable memory characteristics, having a large memory window (6.5 V), low-operating voltage (0 to -5 V), faster P/E switching speed (50/500 μs), long retention time (>10 years), and excellent fatigue P/E cycle (>105) due to the boosting effect, amplification effect, and energy band distortion of nitride from the large polarization. All these characteristics correspond to the best performances among conventional flash cells reported so far.

Axin and GSK3- control Smad3 protein stability and modulate TGF- signaling.

Science.gov (United States)

Guo, Xing; Ramirez, Alejandro; Waddell, David S; Li, Zhizhong; Liu, Xuedong; Wang, Xiao-Fan

2008-01-01

The broad range of biological responses elicited by transforming growth factor-beta (TGF-beta) in various types of tissues and cells is mainly determined by the expression level and activity of the effector proteins Smad2 and Smad3. It is not fully understood how the baseline properties of Smad3 are regulated, although this molecule is in complex with many other proteins at the steady state. Here we show that nonactivated Smad3, but not Smad2, undergoes proteasome-dependent degradation due to the concerted action of the scaffolding protein Axin and its associated kinase, glycogen synthase kinase 3-beta (GSK3-beta). Smad3 physically interacts with Axin and GSK3-beta only in the absence of TGF-beta. Reduction in the expression or activity of Axin/GSK3-beta leads to increased Smad3 stability and transcriptional activity without affecting TGF-beta receptors or Smad2, whereas overexpression of these proteins promotes Smad3 basal degradation and desensitizes cells to TGF-beta. Mechanistically, Axin facilitates GSK3-beta-mediated phosphorylation of Smad3 at Thr66, which triggers Smad3 ubiquitination and degradation. Thr66 mutants of Smad3 show altered protein stability and hence transcriptional activity. These results indicate that the steady-state stability of Smad3 is an important determinant of cellular sensitivity to TGF-beta, and suggest a new function of the Axin/GSK3-beta complex in modulating critical TGF-beta/Smad3-regulated processes during development and tumor progression.

Hepatic progenitor cell resistance to TGF-β1's proliferative and apoptotic effects

International Nuclear Information System (INIS)

Clark, J. Brian; Rice, Lisa; Sadiq, Tim; Brittain, Evan; Song, Lujun; Wang Jian; Gerber, David A.

2005-01-01

The success of hepatocellular therapies using stem or progenitor cell populations is dependent upon multiple factors including the donor cell, microenvironment, and etiology of the liver injury. The following experiments investigated the impact of TGF-β1 on a previously described population of hepatic progenitor cells (HPC). The majority of the hepatic progenitor cells were resistant to endogenously produced TGF-β1's proapoptotic and anti-proliferative effects unlike more well-differentiated cellular populations (e.g., mature hepatocytes). Surprisingly, in vitro TGF-β1 supplementation significantly inhibited de novo hepatic progenitor cell colony formation possibly via an indirect mechanism(s). Therefore despite the HPC's direct resistance to supplemental TGF-β1, this cytokine's inhibitory effect on colony formation could have a potential negative impact on the use of these cells as a therapy for patients with liver disease

PENGEMBANGAN EVALUASI PEMBELAJARAN BERBASIS MULTIMEDIA DENGAN FLASH, PHP, DAN MySQL

Directory of Open Access Journals (Sweden)

Hadi Sutopo

2012-01-01

Full Text Available Computer-Based Testing (CBT program was launched for years to give test takers the options of taking computerized version of test. The application which generates academic score is developed as a server-side with Adobe Flash. Flash is well known as a powerful and dynamic front-end for the Web. However, Flash is also great interface for server-side applications. PHP can launch server-side script using Flash as a front-end and pass variables back and forth between Flash and the PHP pages. Along with PHP, MySQL can be used to store data and later retrieve it. Using Flash as a front-end, data and variables are passed between the MySQL database, PHP, and Flash to enhance application's functionality in managing databases.

Disruption of TGF-β signaling in smooth muscle cell prevents flow-induced vascular remodeling

Energy Technology Data Exchange (ETDEWEB)

Gao, Fu [Department of Vascular Surgery, Peking University People’s Hospital, Beijing (China); Chambon, Pierre [Institut de Génétique et de Biologie Moléculaire et Cellulaire (CNRS UMR7104, INSERM U596, ULP, Collége de France) and Institut Clinique de la Souris, ILLKIRCH, Strasbourg (France); Tellides, George [Department of Surgery, Interdepartmental Program in Vascular Biology and Therapeutics, Yale University School of Medicine, New Haven, CT (United States); Kong, Wei [Department of Physiology and Pathophysiology, Basic Medical College of Peking University, Beijing (China); Zhang, Xiaoming, E-mail: rmygxgwk@163.com [Department of Vascular Surgery, Peking University People’s Hospital, Beijing (China); Li, Wei [Department of Vascular Surgery, Peking University People’s Hospital, Beijing (China)

2014-11-07

Highlights: • TGF-β signaling in SMC contributes to the flow-induced vascular remodeling. • Disruption of TGF-β signaling in SMC can prevent this process. • Targeting SM-specific Tgfbr2 could be a novel therapeutic strategy for vascular remodeling. - Abstract: Transforming growth factor-β (TGF-β) signaling has been prominently implicated in the pathogenesis of vascular remodeling, especially the initiation and progression of flow-induced vascular remodeling. Smooth muscle cells (SMCs) are the principal resident cells in arterial wall and are critical for arterial remodeling. However, the role of TGF-β signaling in SMC for flow-induced vascular remodeling remains unknown. Therefore, the goal of our study was to determine the effect of TGF-β pathway in SMC for vascular remodeling, by using a genetical smooth muscle-specific (SM-specific) TGF-β type II receptor (Tgfbr2) deletion mice model. Mice deficient in the expression of Tgfbr2 (MyhCre.Tgfbr2{sup f/f}) and their corresponding wild-type background mice (MyhCre.Tgfbr2{sup WT/WT}) underwent partial ligation of left common carotid artery for 1, 2, or 4 weeks. Then the carotid arteries were harvested and indicated that the disruption of Tgfbr2 in SMC provided prominent inhibition of vascular remodeling. And the thickening of carotid media, proliferation of SMC, infiltration of macrophage, and expression of matrix metalloproteinase (MMP) were all significantly attenuated in Tgfbr2 disruption mice. Our study demonstrated, for the first time, that the TGF-β signaling in SMC plays an essential role in flow-induced vascular remodeling and disruption can prevent this process.

Response of the human circadian system to millisecond flashes of light.

Directory of Open Access Journals (Sweden)

Jamie M Zeitzer

Full Text Available Ocular light sensitivity is the primary mechanism by which the central circadian clock, located in the suprachiasmatic nucleus (SCN, remains synchronized with the external geophysical day. This process is dependent on both the intensity and timing of the light exposure. Little is known about the impact of the duration of light exposure on the synchronization process in humans. In vitro and behavioral data, however, indicate the circadian clock in rodents can respond to sequences of millisecond light flashes. In a cross-over design, we tested the capacity of humans (n = 7 to respond to a sequence of 60 2-msec pulses of moderately bright light (473 lux given over an hour during the night. Compared to a control dark exposure, after which there was a 3.5±7.3 min circadian phase delay, the millisecond light flashes delayed the circadian clock by 45±13 min (p<0.01. These light flashes also concomitantly increased subjective and objective alertness while suppressing delta and sigma activity (p<0.05 in the electroencephalogram (EEG. Our data indicate that phase shifting of the human circadian clock and immediate alerting effects can be observed in response to brief flashes of light. These data are consistent with the hypothesis that the circadian system can temporally integrate extraordinarily brief light exposures.

The role of TGF-β and its crosstalk with RAC1/RAC1b signaling in breast and pancreas carcinoma.

Science.gov (United States)

Melzer, Catharina; Hass, Ralf; von der Ohe, Juliane; Lehnert, Hendrik; Ungefroren, Hendrik

2017-05-12

This article focusses on the role of TGF-β and its signaling crosstalk with the RHO family GTPases RAC1 and RAC1b in the progression of breast and pancreatic carcinoma. The aggressive nature of these tumor types is mainly due to metastatic dissemination. Metastasis is facilitated by desmoplasia, a peculiar tumor microenvironment and the ability of the tumor cells to undergo epithelial-mesenchymal transition (EMT) and to adopt a motile and invasive phenotype. These processes are controlled entirely or in part by TGF-β and the small RHO GTPase RAC1 with both proteins acting as tumor promoters in late-stage cancers. Data from our and other studies point to signaling crosstalk between TGF-β and RAC1 and the related isoform, RAC1b, in pancreatic and mammary carcinoma cells. Based on the exciting observation that RAC1b functions as an endogenous inhibitor of RAC1, we propose a model on how the relative abundance or activity of RAC1 and RAC1b in the tumor cells may determine their responses to TGF-β and, ultimately, the metastatic capacity of the tumor.

History of hot flashes and aortic calcification among postmenopausal women.

Science.gov (United States)

Thurston, Rebecca C; Kuller, Lewis H; Edmundowicz, Daniel; Matthews, Karen A

2010-03-01

Menopausal hot flashes are considered largely a quality-of-life issue. However, emerging research also links hot flashes to cardiovascular risk. In some investigations, this risk is particularly apparent among women using hormone therapy. The aim of this study was to determine whether a longer history of reported hot flashes over the study period was associated with greater aortic and coronary artery calcification. Interactions with hormone therapy use were examined in an exploratory fashion. Participants included 302 women participating in the Healthy Women Study, a longitudinal study of cardiovascular risk during perimenopause and postmenopause, which was initiated in 1983. Hot flashes (any/none) were assessed when women were 1, 2, 5, and 8 years postmenopausal. Electron beam tomography measures of coronary artery calcification and aortic calcification were completed in 1997-2004. Associations between the number of visits with report of hot flashes, divided by the number of visits attended, and aortic or coronary artery calcification (transformed) were examined in linear regression models. Interactions by hormone therapy use were evaluated. Among women using hormone therapy, a longer history of reported hot flashes was associated with increased aortic calcification, controlling for traditional cardiovascular risk factors (b = 2.87, SE = 1.21, P history of hot flashes and coronary artery calcification. Among postmenopausal women using hormone therapy, a longer history of reported hot flashes measured prospectively was associated with increased aortic calcification, controlling for traditional cardiovascular risk factors. Hot flashes may signal adverse cardiovascular changes among certain postmenopausal women.

FPGA Flash Memory High Speed Data Acquisition

Science.gov (United States)

Gonzalez, April

2013-01-01

The purpose of this research is to design and implement a VHDL ONFI Controller module for a Modular Instrumentation System. The goal of the Modular Instrumentation System will be to have a low power device that will store data and send the data at a low speed to a processor. The benefit of such a system will give an advantage over other purchased binary IP due to the capability of allowing NASA to re-use and modify the memory controller module. To accomplish the performance criteria of a low power system, an in house auxiliary board (Flash/ADC board), FPGA development kit, debug board, and modular instrumentation board will be jointly used for the data acquisition. The Flash/ADC board contains four, 1 MSPS, input channel signals and an Open NAND Flash memory module with an analog to digital converter. The ADC, data bits, and control line signals from the board are sent to an Microsemi/Actel FPGA development kit for VHDL programming of the flash memory WRITE, READ, READ STATUS, ERASE, and RESET operation waveforms using Libero software. The debug board will be used for verification of the analog input signal and be able to communicate via serial interface with the module instrumentation. The scope of the new controller module was to find and develop an ONFI controller with the debug board layout designed and completed for manufacture. Successful flash memory operation waveform test routines were completed, simulated, and tested to work on the FPGA board. Through connection of the Flash/ADC board with the FPGA, it was found that the device specifications were not being meet with Vdd reaching half of its voltage. Further testing showed that it was the manufactured Flash/ADC board that contained a misalignment with the ONFI memory module traces. The errors proved to be too great to fix in the time limit set for the project.

Immunohistochemical expression of TGF-β1 and MMP-9 in periapical lesions.

Science.gov (United States)

Álvares, Pâmella Recco; Arruda, José Alcides Almeida de; Silva, Leorik Pereira da; Nascimento, George João Ferreira do; Silveira, Maria Fonseca da; Sobral, Ana Paula Veras

2017-07-03

The objective of this study was to evaluate the expression of matrix metalloproteinase 9 (MMP-9) and transforming growth factor beta (TGF-β1) in periapical lesion samples correlated with the intensity of the inflammatory infiltrate and thickness of the epithelial lining. Forty-five cases of periapical lesions (23 periapical granulomas and 22 radicular cysts) were subjected to morphological and immunohistochemical analyses using anti-MMP-9 and anti-TGF-β1 antibodies. The data were analyzed using the following tests: non-parametric Mann-Whitney, chi-square, Fisher's exact test and Spearman's correlation test (Pperiapical granulomas presented infiltrate grade III, in contrast with 32% of radicular cysts (Pcysts revealed the presence of atrophic epithelium in 86% of the cysts. The immunostaining of MMP-9 was score 2 in 67% of the granulomas and 77% of the cysts. Both lesions were predominantly score 1 for TGF-β1. Significant differences were confirmed between the expression scores of TGF-β1 and MMP-9 in periapical granulomas (p = 0.004) and in radicular cysts (p periapical granulomas and radicular cysts. This immunoregulatory cytokine seems more representative in asymptomatic lesions. The extracellular matrix remodeling process dependent on MMP-9 seems to be similar for both periapical granulomas and radicular cysts. TGF-β1 and MMP-9 may play an important role in the maintenance of periapical lesions.

A Hot Downflowing Model Atmosphere for Umbral Flashes and the Physical Properties of Their Dark Fibrils

Energy Technology Data Exchange (ETDEWEB)

Henriques, V. M. J.; Mathioudakis, M. [Astrophysics Research Centre, School of Mathematics and Physics, Queen’s University Belfast, BT7 1NN, Northern Ireland (United Kingdom); Socas-Navarro, H. [Instituto de Astrofísica de Canarias, Avda vía Láctea S/N, E-38205 La Laguna, Tenerife (Spain); Rodríguez, J. de la Cruz, E-mail: v.henriques@qub.ac.uk [Institute for Solar Physics, Department of Astronomy, Stockholm University, AlbaNova University Centre, SE-106 91 Stockholm (Sweden)

2017-08-20

We perform non-LTE inversions in a large set of umbral flashes, including the dark fibrils visible within them, and in the quiescent umbra by using the inversion code NICOLE on a set of full Stokes high-resolution Ca ii λ 8542 observations of a sunspot at disk center. We find that the dark structures have Stokes profiles that are distinct from those of the quiescent and flashed regions. They are best reproduced by atmospheres that are more similar to the flashed atmosphere in terms of velocities, even if with reduced amplitudes. We also find two sets of solutions that finely fit the flashed profiles: a set that is upflowing, featuring a transition region that is deeper than in the quiescent case and preceded by a slight dip in temperature, and a second solution with a hotter atmosphere in the chromosphere but featuring downflows close to the speed of sound at such heights. Such downflows may be related, or even dependent, on the presence of coronal loops, rooted in the umbra of sunspots, as is the case in the region analyzed. Similar loops have been recently observed to have supersonic downflows in the transition region and are consistent with the earlier “sunspot plumes,” which were invariably found to display strong downflows in sunspots. Finally, we find, on average, a magnetic field reduction in the flashed areas, suggesting that the shock pressure is moving field lines in the upper layers.

Ionizing radiation predisposes non-malignant human mammaryepithelial cells to undergo TGF beta-induced epithelial to mesenchymaltransition

Energy Technology Data Exchange (ETDEWEB)

Andarawewa, Kumari L.; Erickson, Anna C.; Chou, William S.; Costes, Sylvain; Gascard, Philippe; Mott, Joni D.; Bissell, Mina J.; Barcellos-Hoff, Mary Helen

2007-04-06

Transforming growth factor {beta}1 (TGF{beta}) is a tumor suppressor during the initial stage of tumorigenesis, but it can switch to a tumor promoter during neoplastic progression. Ionizing radiation (IR), both a carcinogen and a therapeutic agent, induces TGF{beta}, activation in vivo. We now show that IR sensitizes human mammary epithelial cells (HMEC) to undergo TGF{beta}-mediated epithelial to mesenchymal transition (EMT). Non-malignant HMEC (MCF10A, HMT3522 S1 and 184v) were irradiated with 2 Gy shortly after attachment in monolayer culture, or treated with a low concentration of TGF{beta} (0.4 ng/ml), or double-treated. All double-treated (IR+TGF{beta}) HMEC underwent a morphological shift from cuboidal to spindle-shaped. This phenotype was accompanied by decreased expression of epithelial markers E-cadherin, {beta}-catenin and ZO-1, remodeling of the actin cytoskeleton, and increased expression of mesenchymal markers N-cadherin, fibronectin and vimentin. Furthermore, double-treatment increased cell motility, promoted invasion and disrupted acinar morphogenesis of cells subsequently plated in Matrigel{trademark}. Neither radiation nor TGF{beta} alone elicited EMT, even though IR increased chronic TGF{beta} signaling and activity. Gene expression profiling revealed that double treated cells exhibit a specific 10-gene signature associated with Erk/MAPK signaling. We hypothesized that IR-induced MAPK activation primes non-malignant HMEC to undergo TGF{beta}-mediated EMT. Consistent with this, Erk phosphorylation were transiently induced by irradiation, persisted in irradiated cells treated with TGF{beta}, and treatment with U0126, a Mek inhibitor, blocked the EMT phenotype. Together, these data demonstrate that the interactions between radiation-induced signaling pathways elicit heritable phenotypes that could contribute to neoplastic progression.

Hsc70 facilitates TGF-β-induced activation of Smad2/3 in fibroblastic NRK-49F cells

Energy Technology Data Exchange (ETDEWEB)

Ikezaki, Midori; Higashimoto, Natsuki; Matsumura, Ko; Ihara, Yoshito, E-mail: y-ihara@wakayama-med.ac.jp

2016-08-26

Heat-shock cognate protein 70 (Hsc70), a molecular chaperone constitutively expressed in the cell, is involved in the regulation of several cellular signaling pathways. In this study, we found that TGF-β-induced phosphorylation and nuclear translocation of Smad2/3 were suppressed in fibroblastic NRK-49F cells treated with small interfering RNA (siRNA) for Hsc70. In the cells underexpressing Hsc70, transcriptional induction of connective tissue growth factor (CTGF), a target gene of the TGF-β signaling, was also suppressed in the early phase of TGF-β stimulation. Upon stimulation with TGF-β, Hsc70 interacted with Smad2/3, suggesting functional interactions of Hsc70 and Smad2/3 for the activation of TGF-β-induced Smad signaling. Although the expression of heat-shock protein 70 (Hsp70) was upregulated in the cells treated with Hsc70 siRNA, TGF-β-induced Smad activation was not affected in the cells overexpressing Hsp70. Collectively, these results indicate that Hsc70, but not Hsp70, supportively regulates TGF-β-induced Smad signaling in NRK-49F cells. - Highlights: • Hsc70 siRNA treatment suppressed the expression of Hsc70 but induced the expression of Hsp70 in NRK-49F cells. • Hsc70 siRNA treatment suppressed the activation of Smad2/3 in the cells treated with TGF-β. • Hsc70 interacted with Smad2/3 on stimulation with TGF-β in the cells. • Hsp70 did not influence the TGF-β-induced activation of Smad2/3 in the cells overexpressing Hsp70.

Flash Mob Science - Increasing Seismic Hazard Awareness and Preparedness in Oregon

Science.gov (United States)

Hoffman, J. S.; Lownsbery, D. S.

2015-12-01

Living in a region of imminent threat of a magnitude-9.0 (M­­­w ≈ ­9) earthquake is a daily reality for the millions of people predicted to be directly affected by a full rupture of the Cascadia Subduction Zone (CSZ), a fault line extending for hundreds of miles off the western coast of North America. Many coastal residents and visitors will also be affected by the tsunami caused by the rupture. How can the scientific community effectively communicate with those who are unaware of the threat and unprepared to respond? We are studying the effects of a novel approach to science outreach we have called Flash Mob Science. You have probably seen examples of flash mobs staging dynamic musical and dance routines to unsuspecting audiences. Similarly, Flash Mob Science takes the challenging (and often avoided) topic of earthquake and tsunami awareness and preparedness to unsuspecting audiences. However, Flash Mob Science seeks to move beyond having an audience of observers by engaging others as participants who enact important roles in an unfolding drama. We simulate the effects of seismic and tsunami events (e.g., prolonged surface shaking, falling debris, repeated tsunami surges) and model best practices in response (e.g., "Drop, Cover, Hold On" and moving quickly to high ground). True to the general flash mob model, when the Cascadia event inevitably does occur, it will come suddenly, and everyone affected will unavoidably be involved as actors in a real-life drama of immense scale. We seek to embed the learning of basic understandings and practices for an actual Cascadia event in a very small-scale, memorable, and sometimes even humorous, dramatization. We present here the lessons we have learned in the background, planning, and implementation of Flash Mob Science. We highlight the successes, limitations, and preliminary results evaluating the effectiveness of this outreach in developing learners' understandings and preparedness in an Oregon community affected by

Connective tissue growth factor mediates TGF-β1-induced low-grade serous ovarian tumor cell apoptosis.

Science.gov (United States)

Cheng, Jung-Chien; Chang, Hsun-Ming; Leung, Peter C K

2017-10-17

Ovarian low-grade serous carcinoma (LGSC) is a rare disease and is now considered to be a distinct entity from high-grade serous carcinoma (HGSC), which is the most common and malignant form of epithelial ovarian cancer. Connective tissue growth factor (CTGF) is a secreted matricellular protein that has been shown to modulate many biological functions by interacting with multiple molecules in the microenvironment. Increasing evidence indicates that aberrant expression of CTGF is associated with cancer development and progression. Transforming growth factor-β1 (TGF-β1) is a well-known molecule that can strongly up-regulate CTGF expression in different types of normal and cancer cells. Our previous study demonstrated that TGF-β1 induces apoptosis of LGSC cells. However, the effect of TGF-β1 on CTGF expression in LGSC needs to be defined. In addition, whether CTGF mediates TGF-β1-induced LGSC cell apoptosis remains unknown. In the present study, we show that TGF-β1 treatment up-regulates CTGF expression by activating SMAD3 signaling in two human LGSC cell lines. Additionally, siRNA-mediated CTGF knockdown attenuates TGF-β1-induced cell apoptosis. Moreover, our results show that the inhibitory effect of the CTGF knockdown on TGF-β1-induced cell apoptosis is mediated by down-regulating SMAD3 expression. This study demonstrates an important role for CTGF in mediating the pro-apoptotic effects of TGF-β1 on LGCS.

Heavy ions light flashes and brain functions: recent observations at accelerators and in spaceflight

International Nuclear Information System (INIS)

Narici, L

2008-01-01

Interactions between ionizing radiation in space and brain functions, and the related risk assessments, are among the major concerns when programming long permanence in space, especially when outside the protective shield of the Earth's magnetosphere. The light flashes (LF) observed by astronauts in space, mostly when dark adapted, are an example of these interactions; investigations in space and on the ground showed that these effects can originate with the action of ionizing radiation in the eye. Recent findings from ALTEA, an interdisciplinary and multiapproach program devoted to the study of different aspects of the radiation-brain functions interaction, are presented in this paper. These include: (i) study of radiation passing through the astronauts' eyes in the International Space Station (∼20 ions min -1 , excluding H and fast and very slow He), measured in conjunction with reporting of the perception of LF; (ii) preliminary electrophysiological evidence of these events in astronauts and in patients during heavy ion therapy; and (iii) in vitro results showing the radiation driven activation of rhodopsin at the start of the phototransduction cascade in the process of vision. These results are in agreement with our previous work on mice. A brief but complete summary of the earlier works is also reported to permit a discussion of the results

Pokemon (FBI-1) interacts with Smad4 to repress TGF-β-induced transcriptional responses.

Science.gov (United States)

Yang, Yutao; Cui, Jiajun; Xue, Feng; Zhang, Chuanfu; Mei, Zhu; Wang, Yue; Bi, Mingjun; Shan, Dapeng; Meredith, Alex; Li, Hui; Xu, Zhi-Qing David

2015-03-01

Pokemon, an important proto-oncoprotein, is a transcriptional repressor that belongs to the POK (POZ and Krüppel) family. Smad4, a key component of TGF-β pathway, plays an essential role in TGF-β-induced transcriptional responses. In this study, we show that Pokemon can interact directly with Smad4 both in vitro and in vivo. Overexpression of Pokemon decreases TGF-β-induced transcriptional activities, whereas knockdown of Pokemon increases these activities. Interestingly, Pokemon does not affect activation of Smad2/3, formation of Smads complex, or DNA binding activity of Smad4. TGF-β1 treatment increases the interaction between Pokemon and Smad4, and also enhances the recruitment of Pokemon to Smad4-DNA complex. In addition, we also find that Pokemon recruits HDAC1 to Smad4 complex but decreases the interaction between Smad4 and p300/CBP. Taken together, all these data suggest that Pokemon is a new partner of Smad4 and plays a negative role in TGF-β pathway. Copyright © 2014. Published by Elsevier B.V.

Mesenchymal stem cells maintain TGF-beta-mediated chondrogenic phenotype in alginate bead culture

DEFF Research Database (Denmark)

Mehlhorn, A T; Schmal, H; Kaiser, S

2006-01-01

cultured in osteogenic medium after TGF-beta-mediated chondroinduction. Gene expression of col2a1, aggrecan, COMP, alkaline phosphatase (AP), and correlating protein synthesis was analyzed. After short-term stimulation with TGF-beta, MSCs maintained a chondrogenic phenotype. Chondrogenic gene expression...

The design of the light-flash warning light

Science.gov (United States)

Wang, Junli

2018-05-01

In today's society, the warning light has been used widely in people's daily life and various industries and agricultures. It is important to protect people's life and security. Light-flashing warning light is a kind of warning light control equipment which can control warning light automatically open and work in the state of blinking after dark, and it can automatically shut down after the dawn. It can achieve the flashing light automatic control and dual function. At present, light-flashing warning lights are mainly used in the projects of municipal construction. It is helpful to warn people and vehicles that passed in the construction site and ensure personal safety through using light-flashing warning light. Its design is simple, its performance is stable and it is also very convince to use it.

High-Energy Radiation from Thunderstorms with ADELE: TGFs, Steps, and Glows

Science.gov (United States)

Smith, David M.; Kelley, Nicole; Martinez-McKinney, Forest; Zhang, Zi Yan; Hazelton, Bryna; Grefenstette, Brian; Splitt, Michael; Lazarus, Steven; Ulrich, William; Levine, Steven;

Experimental and numerical investigations on flashing-induced instabilities in a single channel

Energy Technology Data Exchange (ETDEWEB)

Marcel, Christian P.; Rohde, M.; Van Der Hagen, T.H.J.J. [Department of Physics of Nuclear Reactors, Delft University of Technology (TUDelft), Delft, 2629 JB (Netherlands)

2009-11-15

During the start-up phase, natural circulation BWRs (NC-BWRs) need to be operated at low pressure conditions. Such conditions favor flashing-induced instabilities due to the large hydrostatic pressure drop induced by the tall chimney. Moreover, in novel NC-BWR designs the steam separation is performed in the steam separators which create large pressure drops at the chimney outlet, which effect on stability has not been investigated yet. In this work, flashing-induced oscillations occurring in a tall, bottom heated channel are numerically investigated by using a simple linear model with three regions and an accurate implementation for estimating the water properties. The model is used to investigate flashing-induced instabilities in a channel for different values of the core inlet friction value. The results are compared with experiments obtained by using the CIRCUS facility at the same conditions, showing a good agreement. In addition, the experiments on flashing-induced instabilities are presented in a novel manner allowing visualizing new details of the phenomenon numerical stability investigations on the effect of the friction distribution are also done. It is found that by increasing the total restriction in the channel the system is destabilized. In addition, the chimney outlet restriction has a stronger destabilizing effect than the core inlet restriction. A stable two-phase region is observed prior to the instabilities in the experiments and the numerical simulations which may help to pressurize the vessel of NC-BWRs and thus reducing the effects of flashing instabilities during start-up. (author)

Angiotensin II increases CTGF expression via MAPKs/TGF-{beta}1/TRAF6 pathway in atrial fibroblasts

Energy Technology Data Exchange (ETDEWEB)

Gu, Jun [Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiaotong University School of medicine, Shanghai (China); Liu, Xu, E-mail: xkliuxu@yahoo.cn [Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiaotong University School of medicine, Shanghai (China); Wang, Quan-xing, E-mail: shmywqx@126.com [National Key Laboratory of Medical Immunology, Second Military Medical University, Shanghai (China); Tan, Hong-wei [Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiaotong University School of medicine, Shanghai (China); Guo, Meng [National Key Laboratory of Medical Immunology, Second Military Medical University, Shanghai (China); Jiang, Wei-feng; Zhou, Li [Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiaotong University School of medicine, Shanghai (China)

2012-10-01

The activation of transforming growth factor-{beta}1(TGF-{beta}1)/Smad signaling pathway and increased expression of connective tissue growth factor (CTGF) induced by angiotensin II (AngII) have been proposed as a mechanism for atrial fibrosis. However, whether TGF{beta}1/non-Smad signaling pathways involved in AngII-induced fibrogenetic factor expression remained unknown. Recently tumor necrosis factor receptor associated factor 6 (TRAF6)/TGF{beta}-associated kinase 1 (TAK1) has been shown to be crucial for the activation of TGF-{beta}1/non-Smad signaling pathways. In the present study, we explored the role of TGF-{beta}1/TRAF6 pathway in AngII-induced CTGF expression in cultured adult atrial fibroblasts. AngII (1 {mu}M) provoked the activation of P38 mitogen activated protein kinase (P38 MAPK), extracellular signal-regulated kinase 1/2(ERK1/2) and c-Jun NH(2)-terminal kinase (JNK). AngII (1 {mu}M) also promoted TGF{beta}1, TRAF6, CTGF expression and TAK1 phosphorylation, which were suppressed by angiotensin type I receptor antagonist (Losartan) as well as p38 MAPK inhibitor (SB202190), ERK1/2 inhibitor (PD98059) and JNK inhibitor (SP600125). Meanwhile, both TGF{beta}1 antibody and TRAF6 siRNA decreased the stimulatory effect of AngII on TRAF6, CTGF expression and TAK1 phosphorylation, which also attenuated AngII-induced atrial fibroblasts proliferation. In summary, the MAPKs/TGF{beta}1/TRAF6 pathway is an important signaling pathway in AngII-induced CTGF expression, and inhibition of TRAF6 may therefore represent a new target for reversing Ang II-induced atrial fibrosis. -- Highlights: Black-Right-Pointing-Pointer MAPKs/TGF{beta}1/TRAF6 participates in AngII-induced CTGF expression in atrial fibroblasts. Black-Right-Pointing-Pointer TGF{beta}1/TRAF6 participates in AngII-induced atrial fibroblasts proliferation. Black-Right-Pointing-Pointer TRAF6 may represent a new target for reversing Ang II-induced atrial fibrosis.

Berberine Suppresses Cell Motility Through Downregulation of TGF-β1 in Triple Negative Breast Cancer Cells

Directory of Open Access Journals (Sweden)

Sangmin Kim

2018-01-01

Full Text Available Background/Aims: Transforming growth factor-beta proteins (TGF-βs are multifunctional growth factors and powerful modulators of the epithelial-mesenchymal transition (EMT in a variety of cancer types including breast and lung cancer cells. Here, we demonstrated the inhibitory effect of berberine (BBR on tumor growth and metastasis of triple negative breast cancer (TNBC cells via suppression of TGF-β1 expression. Methods: The levels of mRNA expression were analyzed by real-time PCR. The levels of MMP-2, MMP-9 and TGF-β1 protein expression were analyzed by zymography and confocal microscopy, respectively. Cell migration was analyzed by wound healing assay. Tumorigenicity of TNBC cells such as tumor growth and metastasis was analyzed using xenograft models. Results: In a clinical data set, aberrant TGF-β1 expression was associated with poor prognosis of breast cancer patients. Our in vitro results using TNBC cells showed that the expression levels of matrix metalloproteinase (MMP-2 and MMP-9 and the capacity for cell migration were increased by TGF-β1 treatment. In contrast, basal levels of MMP-2 and MMP-9 were suppressed by a specific TGF-β receptor I inhibitor, SB431542. In addition, TGF-β1–induced MMP-2 and MMP-9 expression and cell migration were decreased by SB431542. Interestingly, we showed for the first time that BBR decreased the level of TGF-β1, but not TGF-β2, in TNBC cells. Furthermore, BBR significantly decreased the level of MMP-2 expression as well as the capacity for cell migration in TNBC cells. Finally, we examined the effect of BBR on in vivo tumor growth and lung metastasis in MDA-MB231 and 4T1 breast cancer xenograft models and showed that both were significantly decreased following BBR treatment. Conclusion: BBR suppresses tumorigenicity of TNBC cells through inhibition of TGF-β1 expression. Therefore, we demonstrate that BBR could be a promising drug for treatment of TNBC.

Role of dihydrotestosterone (DHT) on TGF-β1 signaling pathway in epithelial ovarian cancer cells.

Science.gov (United States)

Kohan-Ivani, Karla; Gabler, Fernando; Selman, Alberto; Vega, Margarita; Romero, Carmen

2016-01-01

One of the hypotheses regarding the genesis of epithelial ovarian cancer involves the action of androgens on the proliferation of epithelial ovarian cells, as well as inclusion cysts. The purpose of the present study was to evaluate whether DHT causes changes in the TGF-β1 pathway that might modify the anti-proliferative effect of the latter. The levels of TGF-β1 protein, of its receptors (TGFBR1 and TGFBR2), of Smad2/3 (canonical signaling pathway protein) and of p21 (cell cycle protein) were assessed in ovarian tissues, epithelial ovarian cancer cell lines (A2780) and control cell lines (HOSE) through the use of immunohistochemistry and immunocytochemistry. Additionally, cell lines were treated with 100 nmol/L DHT, 10 ng/mL of TGF-β1 and DHT + TGF-β1 during 72 h in the presence and absence of a siRNA against androgen receptor. After treatment, TGFBR1 and TGFBR2 levels were detected through Western blotting and p21 was assessed through immunocytochemistry. Epithelial ovarian cancer tissues showed a decrease in TGF-β1 I receptor (p DHT, protein levels of TGF-β1 receptors (TGFBR1-TGFBR2) showed a decrease (p DHT (p < 0.001). Overall, our results indicate a defect in the canonical TGF-β signaling pathway in epithelial ovarian cancer caused by androgen action, thus suggesting eventual changes in such tissue proliferation rates.

Measured pulse width of sonoluminescence flashes in the form of resonance radiation

Science.gov (United States)

Giri, Asis; Arakeri, Vijay H.

1998-09-01

Recent studies have shown that the measured flash widths from single and multibubble sonoluminescence are in subnanosecond or even picosecond regime. Here, we provide conclusive evidence for the existence of nanosecond multibubble sonoluminescence. This has become possible by our ability to find a medium from which exclusive sodium D line resonance radiation as a form of sonoluminescence is possible. The measured flash width of this emission is found to be in the range of tens of nanoseconds and is sensitively dependent on experimental parameters. Our finding is important since all the earlier pulse width measurements have been limited to emission with the physical source or species responsible for observed optical radiation not being clearly identified. We propose that the presently observed resonance radiation is from ``soft'' bubble collapse as analyzed by V. Kamath et al. [J. Acoust. Soc. Am. 94, 248 (1993)].

The synergistic induction of bone formation by the osteogenic proteins of the TGF-β supergene family.

Science.gov (United States)

Ripamonti, Ugo; Parak, Ruqayya; Klar, Roland M; Dickens, Caroline; Dix-Peek, Thérèse; Duarte, Raquel

2016-10-01

The momentum to compose this Leading Opinion on the synergistic induction of bone formation suddenly arose when a simple question was formulated during a discussion session on how to boost the often limited induction of bone formation seen in clinical contexts. Re-examination of morphological and molecular data available on the rapid induction of bone formation by the recombinant human transforming growth factor-β3 (hTGF-β3) shows that hTGF-β3 replicates the synergistic induction of bone formation as invocated by binary applications of hOP-1:hTGF-β1 at 20:1 by weight when implanted in heterotopic sites of the rectus abdominis muscle of the Chacma baboon, Papio ursinus. The rapid induction of bone formation in primates by hTGF-β3 may stem from bursts of cladistic evolution, now redundant in lower animal species but still activated in primates by relatively high doses of hTGF-β3. Contrary to rodents, lagomorphs and canines, the three mammalian TGF-β isoforms induce rapid and substantial bone formation when implanted in heterotopic rectus abdominis muscle sites of P. ursinus, with unprecedented regeneration of full thickness mandibular defects with rapid mineralization and corticalization. Provocatively, thus providing potential molecular and biological rationales for the apparent redundancy of osteogenic molecular signals in primates, binary applications of recombinant human osteogenic protein-1 (hOP-1) with low doses of hTGF-β1 and -β3, synergize to induce massive ossicles in heterotopic rectus abdominis, orthotopic calvarial and mandibular sites of P. ursinus. The synergistic binary application of homologous but molecularly different soluble molecular signals has indicated that per force several secreted molecular signals are required singly, synchronously and synergistically to induce optimal osteogenesis. The morphological hallmark of the synergistic induction of bone formation is the rapid differentiation of large osteoid seams enveloping

The echo-enabled harmonic generation options for FLASH II

International Nuclear Information System (INIS)

Deng, Haixiao; Decking, Winfried; Faatz, Bart

2011-03-01

FLASH II is an upgrade to the existing free electron laser (FEL) FLASH. The echo-enabled harmonic generation (EEHG) scheme is proposed to be a potential seeding option of FLASH II. In this paper, the possibility of EEHG operation of FLASH II is investigated for the first time. With a combination of existing numerical codes, i.e. a laser-beam interaction code in an undulator (LBICU), a beam tracking code in a chicane (ELEGANT) and an universal FEL simulating code (GENESIS), the effects of beam energy chirp and coherent synchrotron radiation (CSR) on EEHG operation are studied as well. In addition, several interesting issues concerning EEHG simulation are discussed. (orig.)

Canonical TGF-β Signaling Negatively Regulates Neuronal Morphogenesis through TGIF/Smad Complex-Mediated CRMP2 Suppression.

Science.gov (United States)

Nakashima, Hideyuki; Tsujimura, Keita; Irie, Koichiro; Ishizu, Masataka; Pan, Miao; Kameda, Tomonori; Nakashima, Kinichi

2018-05-16

Functional neuronal connectivity requires proper neuronal morphogenesis and its dysregulation causes neurodevelopmental diseases. Transforming growth factor-β (TGF-β) family cytokines play pivotal roles in development, but little is known about their contribution to morphological development of neurons. Here we show that the Smad-dependent canonical signaling of TGF-β family cytokines negatively regulates neuronal morphogenesis during brain development. Mechanistically, activated Smads form a complex with transcriptional repressor TG-interacting factor (TGIF), and downregulate the expression of a neuronal polarity regulator, collapsin response mediator protein 2. We also demonstrate that TGF-β family signaling inhibits neurite elongation of human induced pluripotent stem cell-derived neurons. Furthermore, the expression of TGF-β receptor 1, Smad4, or TGIF, which have mutations found in patients with neurodevelopmental disorders, disrupted neuronal morphogenesis in both mouse (male and female) and human (female) neurons. Together, these findings suggest that the regulation of neuronal morphogenesis by an evolutionarily conserved function of TGF-β signaling is involved in the pathogenesis of neurodevelopmental diseases. SIGNIFICANCE STATEMENT Canonical transforming growth factor-β (TGF-β) signaling plays a crucial role in multiple organ development, including brain, and mutations in components of the signaling pathway associated with several human developmental disorders. In this study, we found that Smads/TG-interacting factor-dependent canonical TGF-β signaling regulates neuronal morphogenesis through the suppression of collapsin response mediator protein-2 (CRMP2) expression during brain development, and that function of this signaling is evolutionarily conserved in the mammalian brain. Mutations in canonical TGF-β signaling factors identified in patients with neurodevelopmental disorders disrupt the morphological development of neurons. Thus, our

RhoC is essential for TGF-β1-induced invasive capacity of rat ascites hepatoma cells

International Nuclear Information System (INIS)

Mukai, M.; Endo, H.; Iwasaki, T.; Tatsuta, M.; Togawa, A.; Nakamura, H.; Inoue, M.

2006-01-01

Transforming growth factor-β1 (TGF-β1) is a multifunctional growth factor that plays a role in cell proliferation, differentiation, extracellular matrix production, apoptosis, and cell motility. We show here that TGF-β1 increased the invasiveness of MM1 cells, which are a highly invasive clone of rat ascites hepatoma cells. Both mRNA and protein levels of RhoC but not RhoA in TGF-β1-treated MM1 cells increased. In parallel with this increase in expression, RhoC activity was induced by TGF-β1 treatment. When RhoC was overexpressed in MM1 cells, the invasive capacity increased. The RhoC-overexpressing cells formed more nodules than did mock cells when injected into rat peritoneum. Furthermore, when RhoC expression was reduced by transfection with shRNA/RhoC, the invasiveness of MM1 cells decreased with concomitant suppression of RhoC expression. Thus, the induced expression of RhoC by TGF-β1 in MM1 cells plays a critical role in TGF-β1-induced cell migration

Medium range forecasting of Hurricane Harvey flash flooding using ECMWF and social vulnerability data

Science.gov (United States)

Pillosu, F. M.; Jurlina, T.; Baugh, C.; Tsonevsky, I.; Hewson, T.; Prates, F.; Pappenberger, F.; Prudhomme, C.

2017-12-01

During hurricane Harvey the greater east Texas area was affected by extensive flash flooding. Their localised nature meant they were too small for conventional large scale flood forecasting systems to capture. We are testing the use of two real time forecast products from the European Centre for Medium-range Weather Forecasts (ECMWF) in combination with local vulnerability information to provide flash flood forecasting tools at the medium range (up to 7 days ahead). Meteorological forecasts are the total precipitation extreme forecast index (EFI), a measure of how the ensemble forecast probability distribution differs from the model-climate distribution for the chosen location, time of year and forecast lead time; and the shift of tails (SOT) which complements the EFI by quantifying how extreme an event could potentially be. Both products give the likelihood of flash flood generating precipitation. For hurricane Harvey, 3-day EFI and SOT products for the period 26th - 29th August 2017 were used, generated from the twice daily, 18 km, 51 ensemble member ECMWF Integrated Forecast System. After regridding to 1 km resolution the forecasts were combined with vulnerable area data to produce a flash flood hazard risk area. The vulnerability data were floodplains (EU Joint Research Centre), road networks (Texas Department of Transport) and urban areas (Census Bureau geographic database), together reflecting the susceptibility to flash floods from the landscape. The flash flood hazard risk area forecasts were verified using a traditional approach against observed National Weather Service flash flood reports, a total of 153 reported flash floods have been detected in that period. Forecasts performed best for SOT = 5 (hit ratio = 65%, false alarm ratio = 44%) and EFI = 0.7 (hit ratio = 74%, false alarm ratio = 45%) at 72 h lead time. By including the vulnerable areas data, our verification results improved by 5-15%, demonstrating the value of vulnerability information within

A void distribution model-flashing flow

International Nuclear Information System (INIS)

Riznic, J.; Ishii, M.; Afgan, N.

1987-01-01

A new model for flashing flow based on wall nucleations is proposed here and the model predictions are compared with some experimental data. In order to calculate the bubble number density, the bubble number transport equation with a distributed source from the wall nucleation sites was used. Thus it was possible to avoid the usual assumption of a constant bubble number density. Comparisons of the model with the data shows that the model based on the nucleation site density correlation appears to be acceptable to describe the vapor generation in the flashing flow. For the limited data examined, the comparisons show rather satisfactory agreement without using a floating parameter to adjust the model. This result indicated that, at least for the experimental conditions considered here, the mechanistic predictions of the flashing phenomenon is possible on the present wall nucleation based model

Flash memories economic principles of performance, cost and reliability optimization

CERN Document Server

Richter, Detlev

2014-01-01

The subject of this book is to introduce a model-based quantitative performance indicator methodology applicable for performance, cost and reliability optimization of non-volatile memories. The complex example of flash memories is used to introduce and apply the methodology. It has been developed by the author based on an industrial 2-bit to 4-bit per cell flash development project. For the first time, design and cost aspects of 3D integration of flash memory are treated in this book. Cell, array, performance and reliability effects of flash memories are introduced and analyzed. Key performance parameters are derived to handle the flash complexity. A performance and array memory model is developed and a set of performance indicators characterizing architecture, cost and durability is defined.   Flash memories are selected to apply the Performance Indicator Methodology to quantify design and technology innovation. A graphical representation based on trend lines is introduced to support a requirement based pr...

Differences in TGF-β1 signaling and clinicopathologic characteristics of histologic subtypes of gastric cancer.

Science.gov (United States)

Pak, Kyung Ho; Kim, Dong Hoon; Kim, Hyunki; Lee, Do Hyung; Cheong, Jae-Ho

2016-02-04

Aberrant TGF-β1 signaling is suggested to be involved in gastric carcinogenesis. However, the role of TGF-β1 in intestinal-type [i-GC] and diffuse-type [d-GC] gastric cancer remains largely unknown. In this study, we evaluated the expression of TGF-β1 signaling molecules and compared the clinicopathological features of i-GC and d-GC. Patients (n=365, consecutive) who underwent curative gastrectomy for gastric adenocarcinoma in 2005 were enrolled. We performed immunohistochemical staining of TGF-β1, TGF-β1 receptor-2 (TβR2), Smad4, p-ERK1/2, TGF-activated kinase (TAK)1, and p-Akt in 68 paraffin-embedded tumor blocks (33 i-GC and 35 d-GC), scored the expression according to the extent of staining, and evaluated differences between the histologic subtypes. Patients with d-GC differed from those with i-GC as follows: younger and more likely to be female; more aggressive stage; higher recurrence rate. The expression of TGF-β1 and TβR2 was higher in i-GC (P = 0.05 and P Smad4, a representative molecule of the Smad-dependent pathway, was decreased in both subtypes. TAK1 and p-Akt, two major molecules involved in the Smad-independent pathway, were over-expressed (69 ~87% of cases stained), without a statistically significant difference between i-GC and d-GC. Of note, the expression of p-ERK1/2, a Smad-independent pathway, was significantly increased in i-GC (P = 0.008). The clinicopathological characteristics vary in different histologic gastric cancer subtypes. Although TGF-β1 signaling in gastric cancer cells appears hyper-activated in i-GC compared to d-GC, the Smad-dependent pathway seems down-regulated while the Smad-independent pathway seems up-regulated in both histologic subtypes.

Dislocation Motion and the Microphysics of Flash Heating and Weakening of Faults during Earthquakes

Directory of Open Access Journals (Sweden)

Elena Spagnuolo

2016-07-01

release due to the migration of fast-moving dislocations and the conversion of their kinetic energy into heat. From a review of the current natural and experimental observations we speculate that this mechanism tested for calcite-bearing rocks, is a general mechanism operating during flash weakening (e.g., also precursory to flash melting in the case of silicate-bearing rocks for all fault rock types undergoing fast slip acceleration due to the passage of the seismic rupture front.

Method for programming a flash memory

Energy Technology Data Exchange (ETDEWEB)

Brosky, Alexander R.; Locke, William N.; Maher, Conrado M.

2016-08-23

A method of programming a flash memory is described. The method includes partitioning a flash memory into a first group having a first level of write-protection, a second group having a second level of write-protection, and a third group having a third level of write-protection. The write-protection of the second and third groups is disabled using an installation adapter. The third group is programmed using a Software Installation Device.

Environmental Effects on Data Retention in Flash Cells

Science.gov (United States)

Katz, Rich; Flowers, David; Bergevin, Keith

2017-01-01

Flash technology is being utilized in fuzed munition applications and, based on the development of digital logic devices in the commercial world, usage of flash technology will increase. Antifuse technology, prevalent in non-volatile field programmable gate arrays (FPGAs), will eventually be phased out as new devices have not been developed for approximately a decade. The reliance on flash technology presents a long-term reliability issue for both DoD and NASA safety- and mission-critical applications. A thorough understanding of the data retention failure modes and statistics associated with Flash data retention is of vital concern to the fuze safety community. A key retention parameter for a flash cell is the threshold voltage (VTH), which is an indirect indicator of the amount of charge stored on the cells floating gate. This paper will present the results of our on-going tests: long-term storage at 150 C for a small population of devices, neutron radiation exposure, electrostatic discharge (ESD) testing, and the trends of large populations (over 300 devices for each condition) exposed to three difference temperatures: 25 C, 125 C, and 150 C.

Flash photolysis of rhodopsin in the cat retina

International Nuclear Information System (INIS)

Ripps, H.; Mehaffey, L.; Siegel, I.M.; Ernst, W.; Kemp, C.M.

1981-01-01

The bleaching of rhodopsin by short-duration flashes of a xenon discharge lamp was studied in vivo in the cat retina with the aid of a rapid, spectral-scan fundus reflectometer. Difference spectra recorded over a broad range of intensities showed that the bleaching efficacy of high-intensity flashes was less than that of longer duration, steady lights delivering the same amount of energy. Both the empirical results and those derived from a theoretical analysis of flash photolysis indicate that, under the conditions of these experiments, the upper limit of the flash bleaching of rhodopsin in cat is approximately 90%. Although the fact that a full bleach could not be attained is attributable to photoreversal, i.e., the photic regeneration of rhodopsin from its light-sensitive intermediates, the 90% limit is considerably higher than the 50% (or lower) value obtained under other experimental circumstances. Thus, it appears that the duration (approximately 1 ms) and spectral composition of the flash, coupled with the kinetic parameters of the thermal and photic reactions in the cat retina, reduce the light-induced regeneration of rhodopsin to approximately 10%

Applying a coupled hydrometeorological simulation system to flash flood forecasting over the Korean Peninsula

Science.gov (United States)

Ryu, Young; Lim, Yoon-Jin; Ji, Hee-Sook; Park, Hyun-Hee; Chang, Eun-Chul; Kim, Baek-Jo

2017-11-01

In flash flood forecasting, it is necessary to consider not only traditional meteorological variables such as precipitation, evapotranspiration, and soil moisture, but also hydrological components such as streamflow. To address this challenge, the application of high resolution coupled atmospheric-hydrological models is emerging as a promising alternative. This study demonstrates the feasibility of linking a coupled atmospheric-hydrological model (WRF/WRFHydro) with 150-m horizontal grid spacing for flash flood forecasting in Korea. The study area is the Namgang Dam basin in Southern Korea, a mountainous area located downstream of Jiri Mountain (1915 m in height). Under flash flood conditions, the simulated precipitation over the entire basin is comparable to the domain-averaged precipitation, but discharge data from WRF-Hydro shows some differences in the total available water and the temporal distribution of streamflow (given by the timing of the streamflow peak following precipitation), compared to observations. On the basis of sensitivity tests, the parameters controlling the infiltration of excess precipitation and channel roughness depending on stream order are refined and their influence on temporal distribution of streamflow is addressed with intent to apply WRF-Hydro to flash flood forecasting in the Namgang Dam basin. The simulation results from the WRF-Hydro model with optimized parameters demonstrate the potential utility of a coupled atmospheric-hydrological model for forecasting heavy rain-induced flash flooding over the Korean Peninsula.

Desorption of deuterium from beryllium codeposits using flash heating

Energy Technology Data Exchange (ETDEWEB)

Yu, J.H., E-mail: jyu@ferp.ucsd.edu [Center for Energy Research, University of California at San Diego, La Jolla, CA 92093-0417 (United States); Baldwin, M.J.; Doerner, R.P. [Center for Energy Research, University of California at San Diego, La Jolla, CA 92093-0417 (United States); Pitts, R.A. [ITER Organization, Route de Vinon sur Verdon, 13115 Saint Paul Lez Durance (France); Smirnov, R.D. [Center for Energy Research, University of California at San Diego, La Jolla, CA 92093-0417 (United States); Xu, H.W. [General Atomics, P.O. Box 85608, San Diego, CA 92186-5608 (United States)

2013-07-15

As a result of safety concerns, limits will be placed on the allowable tritium inventory retained inside the ITER vacuum vessel. The primary motivation for the present work is to test the proposed method of removing tritium from main chamber codeposits using radiative heat flashing from controlled ITER plasma shutdowns. Detritiation of Be codeposits is studied in the PISCES-B facility using flash-heating by a 10 ms laser with up to 2 MJ/m{sup 2} of absorbed energy density. Three types of codeposits are flash-heated with layer thickness ranging from 0.1 to 1.2 μm. Less than 25% of the D in the Be layer escapes at ITER-relevant flash energy densities and with peak surface temperature up to ∼900 °C. Repetitive flashing with peak surface temperature of 400–500 °C results in an increased population of higher energy trap sites, implying that transient heating which causes appropriate surface temperature excursion redistributes D among codeposit trap sites.

Gun muzzle flash detection using a CMOS single photon avalanche diode

Science.gov (United States)

Merhav, Tomer; Savuskan, Vitali; Nemirovsky, Yael

2013-10-01

Si based sensors, in particular CMOS Image sensors, have revolutionized low cost imaging systems but to date have hardly been considered as possible candidates for gun muzzle flash detection, due to performance limitations, and low SNR in the visible spectrum. In this study, a CMOS Single Photon Avalanche Diode (SPAD) module is used to record and sample muzzle flash events in the visible spectrum, from representative weapons, common on the modern battlefield. SPADs possess two crucial properties for muzzle flash imaging - Namely, very high photon detection sensitivity, coupled with a unique ability to convert the optical signal to a digital signal at the source pixel, thus practically eliminating readout noise. This enables high sampling frequencies in the kilohertz range without SNR degradation, in contrast to regular CMOS image sensors. To date, the SPAD has not been utilized for flash detection in an uncontrolled environment, such as gun muzzle flash detection. Gun propellant manufacturers use alkali salts to suppress secondary flashes ignited during the muzzle flash event. Common alkali salts are compounds based on Potassium or Sodium, with spectral emission lines around 769nm and 589nm, respectively. A narrow band filter around the Potassium emission doublet is used in this study to favor the muzzle flash signal over solar radiation. This research will demonstrate the SPAD's ability to accurately sample and reconstruct the temporal behavior of the muzzle flash in the visible wavelength under the specified imaging conditions. The reconstructed signal is clearly distinguishable from background clutter, through exploitation of flash temporal characteristics.

Flash x-ray cinematography

International Nuclear Information System (INIS)

Stein, W.E.

1976-01-01

Experiments intended to provide an overview of the potential capabilities and limitations of flash x-ray cinematography as a diagnostic technique for a Fast Reactor Safety Test Facility are described. The results provide estimates of the x-ray pulse intensity required to obtain adequate radiographs of an array of fuel pins in a typical reactor configuration. An estimate of the upper limit on the pulse duration imposed by the reactor background radiation was also determined. X-ray cinematography has been demonstrated at a repetition rate limited only by the recording equipment on hand at the time of these measurements. These preliminary results indicate that flash x-ray cinematography of the motion of fuel in a Fast Reactor Test Facility is technically feasible

X-ray Observations at Gaisberg Tower

Directory of Open Access Journals (Sweden)

Pasan Hettiarachchi

2018-01-01

Full Text Available We report the occurrence of X-rays at ground level due to cloud-to-ground flashes of upward-initiated lightning from Gaisberg Tower, in Austria, which is located at an altitude of 1300 m. This is the first observation of X-ray emissions from upward lightning from a tower top located at high altitude. Measurements were carried out using scintillation detectors installed close to the tower top in two phases from 2011 to 2015. X-rays were recorded in three subsequent strokes of three flashes out of the total of 108 flashes recorded in the system during both phases. In contrast to the observations from downward natural or triggered lightning, X-rays were observed only within 10 µs before the subsequent return stroke. This shows that X-rays were emitted when the dart leader was in the vicinity of the tower top, hence during the most intense phase of the dart leader. Both the detected energy and the fluence of X-rays are far lower compared to X-rays from downward natural or rocket-triggered lightning. In addition to the above 108 flashes, an interesting observation of X-rays produced by a nearby downward flash is also presented. The shorter length of dart-leader channels in Gaisberg is suggested as a possible cause of this apparently weaker X-ray production.

Dose-dependent induction of transforming growth factor β (TGF-β) in the lung tissue of fibrosis-prone mice after thoracic irradiation

International Nuclear Information System (INIS)

Ruebe, Claudia E.; Uthe, Daniela; Schmid, Kurt W.; Richter, Klaus D.; Wessel, Jan; Schuck, Andreas; Willich, Norman; Ruebe, Christian

2000-01-01

maximal values at 2 and 4 weeks. The elevated levels of TGF-β mRNA during the latent phase have been found to correlate with immunohistochemical staining of alveolar macrophages. The most striking increase in TGF-β immunoreactivity was seen during the acute phase of pneumonitis. Throughout this observation period, type II pneumocytes and fibroblasts (apart from inflammatory cells) served as important sources of TGF-β expression. Increased TGF-β expression was detected prominently in regions of histopathologic radiation injury. After exposure to a single radiation dose of 6 Gy, the lung tissue revealed only a minor radiation-mediated TGF-β mRNA response. The modest upregulation ranged from 6 hours to 48 hours after irradiation. Corresponding to the only minor histopathologic changes after thoracic irradiation with 6 Gy, measurement of TGF-β mRNA levels during the later time points revealed no significant alterations in comparison to untreated control mice. Conclusions: This study demonstrates an acute and long-lasting increase in the expression of TGF-β in lung tissue following thoracic irradiation with 12 Gy. The predominant localization of TGF-β in areas of inflammatory cell infiltrates and fibrosis suggests involvement of this cytokine in the pathogenesis of radiation-induced pulmonal fibrosis. Further studies should be performed to explore the role of other cytokines in the development of radiation injury. An improved understanding of the underlying mechanisms of pulmonary fibrosis may eventually lead to modulatory intervention at the molecular level to modify the fibrotic process

RAGE and TGF-β1 Cross-Talk Regulate Extracellular Matrix Turnover and Cytokine Synthesis in AGEs Exposed Fibroblast Cells.

Directory of Open Access Journals (Sweden)

Andreea Iren Serban

Full Text Available AGEs accumulation in the skin affects extracellular matrix (ECM turnover and triggers diabetes associated skin conditions and accelerated skin aging. The receptor of AGEs (RAGE has an essential contribution to cellular dysfunction driven by chronic inflammatory responses while TGF-β1 is critical in both dermal homeostasis and inflammation. We investigated the contribution of RAGE and TGF-β1 to the modulation of inflammatory response and ECM turnover in AGEs milieu, using a normal fibroblast cell line. RAGE, TGF-β1, collagen I and III gene and protein expression were upregulated after exposure to AGEs-BSA, and MMP-2 was activated. AGEs-RAGE was pivotal in NF-κB dependent collagen I expression and joined with TGF-β1 to stimulate collagen III expression, probably via ERK1/2 signaling. AGEs-RAGE axis induced upregulation of TGF-β1, TNF-α and IL-8 cytokines. TNF-α and IL-8 were subjected to TGF-β1 negative regulation. RAGE's proinflammatory signaling also antagonized AGEs-TGF-β1 induced fibroblast contraction, suggesting the existence of an inhibitory cross-talk mechanism between TGF-β1 and RAGE signaling. RAGE and TGF-β1 stimulated anti-inflammatory cytokines IL-2 and IL-4 expression. GM-CSF and IL-6 expression appeared to be dependent only on TGF-β1 signaling. Our data also indicated that IFN-γ upregulated in AGEs-BSA milieu in a RAGE and TGF-β1 independent mechanism. Our findings raise the possibility that RAGE and TGF-β1 are both involved in fibrosis development in a complex cross-talk mechanism, while also acting on their own individual targets. This study contributes to the understanding of impaired wound healing associated with diabetes complications.

Phototoxic effects of commercial photographic flash lamp on rat eyes.

Science.gov (United States)

Inoue, Makoto; Shinoda, Kei; Ohde, Hisao; Tezuka, Keiji; Hida, Tetsuo

2006-11-01

To determine whether exposure of the cornea and retina of rats to flashes from a commercial photographic flash lamp is phototoxic. Sprague-Dawley rats were exposed to 10, 100, or 1,000 flashes of the OPTICAM 16M photographic flash lamp (Fujikoeki, Japan) placed 0.1, 1, or 3 m from the eyes. Corneal damage was assessed by a fluorescein staining score, and the retinal damage by eletroretinography (ERG) and histology before and 24 h after exposure. Exposure of the eyes to 1,000 flashes at 0.1 m increased the fluorescein staining score significantly (P = 0.009, the Mann-Whitney test). Scanning electron microscopy (SEM) of the cornea showed a detachment of the epithelial cells from the surface after this exposure. The amplitude of the a-wave was decreased significantly by 23.0% (P = 0.026) of the amplitude before the exposure, and the b-wave by 19.7% (P = 0.0478) following 1,000 flashes at 0.1 m but not by the other exposures. TUNEL-positive cells were present in the outer nuclear layer only after the extreme exposure, but no significant decrease in retinal thickness was seen under any condition. The fluorescein staining score and ERGs recovered to control levels within 1 week. Light exposure to a photographic flash lamp does not induce damage to the cornea and retina except when they are exposed to 1,000 flashes at 0.1 m.

Au Contraire: Gifted in a Flash (Mob)

Science.gov (United States)

Delisle, James R.

2012-01-01

A "flash mob" is defined by Wikipedia as "a large group of people who assemble suddenly in a public place, perform an unusual and pointless act for a brief time, then disperse." Fueled by social media and Smartphones, flash mobs have been used, primarily, as entertaining diversions by addicted techies with (apparently) tons of time on their hands.…

Diagnostic value of combined determination of serum CA19-9 and TGF-β contents in patients with pancreatic cancer

International Nuclear Information System (INIS)

Gong Zheng

2008-01-01

Objective: To study the clinical diagnostic value of combined determination of serum contents of CA19-9 and TGF-β in patients with pancreatic cancer. Methods: Serum CA19-9 (with RIA) and TGF-β (with ELISA) contents were deter- mined in 30 patients with pancreatic cancer and 35 controls. Results: The serum CA19-9 and TGF-β contents in patients with pancreatic cancer were significantly higher than those in controls (P<0.01). The diagnostic sensitivity of CA19-9 for pancreatic cancer was 70.8%, lower than that of TGF-β (80.2%, P<0.05). The diagnostic specificity of CA19-9 and TGF-β was 90.2% and 93.4% respectively. Conclusion: Both determinations of serum CA19-9 and TGF-β contents would yield high specificity for diagnosis of pancreatic cancer. Sensitity of TGF-β determination was higher than that of CA19-9 determination. Combined determination of CA19-9 and TGF-β would improve the diagnostic accuracy in patients with pancreatic cancer. (authors)

Quick Guide to Flash Catalyst

CERN Document Server

Elmansy, Rafiq

2011-01-01

How do you transform user interface designs created in Photoshop or Illustrator into interactive web pages? It's easier than you think. This guide shows you how to use Adobe Flash Catalyst to create interactive UIs and website wireframes for Rich Internet Applications-without writing a single line of code. Ideal for web designers, this book introduces Flash Catalyst basics with detailed step-by-step instructions and screenshots that illustrate every part of the process. You'll learn hands-on how to turn your static design or artwork into working user interfaces that can be implemented in Fla

Combinatorial actions of Tgfβ and Activin ligands promote oligodendrocyte development and CNS myelination.

Science.gov (United States)

Dutta, Dipankar J; Zameer, Andleeb; Mariani, John N; Zhang, Jingya; Asp, Linnea; Huynh, Jimmy; Mahase, Sean; Laitman, Benjamin M; Argaw, Azeb Tadesse; Mitiku, Nesanet; Urbanski, Mateusz; Melendez-Vasquez, Carmen V; Casaccia, Patrizia; Hayot, Fernand; Bottinger, Erwin P; Brown, Chester W; John, Gareth R

2014-06-01

In the embryonic CNS, development of myelin-forming oligodendrocytes is limited by bone morphogenetic proteins, which constitute one arm of the transforming growth factor-β (Tgfβ) family and signal canonically via Smads 1/5/8. Tgfβ ligands and Activins comprise the other arm and signal via Smads 2/3, but their roles in oligodendrocyte development are incompletely characterized. Here, we report that Tgfβ ligands and activin B (ActB) act in concert in the mammalian spinal cord to promote oligodendrocyte generation and myelination. In mouse neural tube, newly specified oligodendrocyte progenitors (OLPs) are first exposed to Tgfβ ligands in isolation, then later in combination with ActB during maturation. In primary OLP cultures, Tgfβ1 and ActB differentially activate canonical Smad3 and non-canonical MAP kinase signaling. Both ligands enhance viability, and Tgfβ1 promotes proliferation while ActB supports maturation. Importantly, co-treatment strongly activates both signaling pathways, producing an additive effect on viability and enhancing both proliferation and differentiation such that mature oligodendrocyte numbers are substantially increased. Co-treatment promotes myelination in OLP-neuron co-cultures, and maturing oligodendrocytes in spinal cord white matter display strong Smad3 and MAP kinase activation. In spinal cords of ActB-deficient Inhbb(-/-) embryos, apoptosis in the oligodendrocyte lineage is increased and OLP numbers transiently reduced, but numbers, maturation and myelination recover during the first postnatal week. Smad3(-/-) mice display a more severe phenotype, including diminished viability and proliferation, persistently reduced mature and immature cell numbers, and delayed myelination. Collectively, these findings suggest that, in mammalian spinal cord, Tgfβ ligands and ActB together support oligodendrocyte development and myelin formation. © 2014. Published by The Company of Biologists Ltd.

Combinatorial actions of Tgfβ and Activin ligands promote oligodendrocyte development and CNS myelination

Science.gov (United States)

Dutta, Dipankar J.; Zameer, Andleeb; Mariani, John N.; Zhang, Jingya; Asp, Linnea; Huynh, Jimmy; Mahase, Sean; Laitman, Benjamin M.; Argaw, Azeb Tadesse; Mitiku, Nesanet; Urbanski, Mateusz; Melendez-Vasquez, Carmen V.; Casaccia, Patrizia; Hayot, Fernand; Bottinger, Erwin P.; Brown, Chester W.; John, Gareth R.

2014-01-01

In the embryonic CNS, development of myelin-forming oligodendrocytes is limited by bone morphogenetic proteins, which constitute one arm of the transforming growth factor-β (Tgfβ) family and signal canonically via Smads 1/5/8. Tgfβ ligands and Activins comprise the other arm and signal via Smads 2/3, but their roles in oligodendrocyte development are incompletely characterized. Here, we report that Tgfβ ligands and activin B (ActB) act in concert in the mammalian spinal cord to promote oligodendrocyte generation and myelination. In mouse neural tube, newly specified oligodendrocyte progenitors (OLPs) are first exposed to Tgfβ ligands in isolation, then later in combination with ActB during maturation. In primary OLP cultures, Tgfβ1 and ActB differentially activate canonical Smad3 and non-canonical MAP kinase signaling. Both ligands enhance viability, and Tgfβ1 promotes proliferation while ActB supports maturation. Importantly, co-treatment strongly activates both signaling pathways, producing an additive effect on viability and enhancing both proliferation and differentiation such that mature oligodendrocyte numbers are substantially increased. Co-treatment promotes myelination in OLP-neuron co-cultures, and maturing oligodendrocytes in spinal cord white matter display strong Smad3 and MAP kinase activation. In spinal cords of ActB-deficient Inhbb−/− embryos, apoptosis in the oligodendrocyte lineage is increased and OLP numbers transiently reduced, but numbers, maturation and myelination recover during the first postnatal week. Smad3−/− mice display a more severe phenotype, including diminished viability and proliferation, persistently reduced mature and immature cell numbers, and delayed myelination. Collectively, these findings suggest that, in mammalian spinal cord, Tgfβ ligands and ActB together support oligodendrocyte development and myelin formation. PMID:24917498

TGF-beta receptor 2 downregulation in tumour-associated stroma worsens prognosis and high-grade tumours show more tumour-associated macrophages and lower TGF-beta1 expression in colon carcinoma: a retrospective study

International Nuclear Information System (INIS)

Bacman, David; Merkel, Susanne; Croner, Roland; Papadopoulos, Thomas; Brueckl, Wolfgang; Dimmler, Arno

2007-01-01

Histological phenotype and clinical behaviour of malignant tumours are not only dependent on alterations in the epithelial cell compartment, but are affected by their interaction with inflammatory cells and tumour-associated stroma. Studies in animal models have shown influence of tumour-associated macrophages (TAM) on histological grade of differentiation in colon carcinoma. Disruption of transforming growth factor beta (TGF-beta) signalling in tumour cells is related to more aggressive clinical behaviour. Expression data of components of this pathway in tumour-associated stroma is limited. Tissue micro arrays of 310 colon carcinomas from curatively resected patients in UICC stage II and III were established. In a first step we quantified amount of CD68 positive TAMs and expression of components of TGF-beta signalling (TGF-beta1, TGF-beta receptors type 1 and 2, Smad 3 and 4) in tumour and associated stroma. Further we analyzed correlation to histological and clinical parameters (histological grade of differentiation (low-grade (i.e. grade 1 and 2) vs. high-grade (i.e. grade 3 and 4)), lymph node metastasis, distant metastasis, 5 year cancer related survival) using Chi-square or Fisher's exact test, when appropriate, to compare frequencies, Kaplan-Meier method to calculate 5-year rates of distant metastases and cancer-related survival and log rank test to compare the rates of distant metastases and survival. To identify independent prognostic factors Cox regression analysis including lymph node status and grading was performed. High-grade tumours and those with lymph node metastases showed higher rates of TAMs and lower expression of TGF-beta1. Loss of nuclear Smad4 expression in tumor was associated with presence of lymph node metastasis, but no influence on prognosis could be demonstrated. Decrease of both TGF-beta receptors in tumour-associated stroma was associated with increased lymph node metastasis and shorter survival. Stromal TGF-beta receptor 2

CCN4/WISP-1 positively regulates chondrogenesis by controlling TGF-β3 function.

Science.gov (United States)

Yoshioka, Yuya; Ono, Mitsuaki; Maeda, Azusa; Kilts, Tina M; Hara, Emilio Satoshi; Khattab, Hany; Ueda, Junji; Aoyama, Eriko; Oohashi, Toshitaka; Takigawa, Masaharu; Young, Marian F; Kuboki, Takuo

2016-02-01

The CCN family of proteins plays important roles in development and homeostasis of bone and cartilage. To understand the role of CCN4 in chondrogenesis, human bone marrow stromal cells (hBMSCs) were transduced with CCN4 adenovirus (adCCN4) or siRNA to CCN4 (siCCN4) in the presence or absence of transforming growth factor-β3 (TGF-β3). Overexpression of CCN4 enhanced TGF-β3-induced SMAD2/3 phosphorylation and chondrogenesis of hBMSCs in an in vitro assay using a micromass culture model. On the other hand, knockdown of CCN4 inhibited the TGF-β3-induced SMAD2/3 phosphorylation and synthesis of cartilage matrix in micromass cultures of hBMSCs. Immunoprecipitation-western blot analysis revealed that CCN4 bound to TGF-β3 and regulated the ability of TGF-β3 to bind to hBMSCs. In vivo analysis confirmed there was a significant decrease in the gene expression levels of chondrocyte markers in cartilage samples from Ccn4-knock out (KO) mice, compared to those from wild type (WT) control. In order to investigate the regenerative properties of the articular cartilage in Ccn4-KO mice, articular cartilage defects were surgically performed in the knee joints of young mice, and the results showed that the cartilage was partially repaired in WT mice, but not in Ccn4-KO mice. In conclusion, these results show, for the first time, that CCN4 has a positive influence on chondrogenic differentiation by modulating the effects of TGF-β3. Copyright © 2015 Elsevier Inc. All rights reserved.

Linkage of regulators of TGF-β activity in the fetal ovary to polycystic ovary syndrome

Science.gov (United States)

Hatzirodos, Nicholas; Bayne, Rosemary A.; Irving-Rodgers, Helen F.; Hummitzsch, Katja; Sabatier, Laetitia; Lee, Sam; Bonner, Wendy; Gibson, Mark A.; Rainey, William E.; Carr, Bruce R.; Mason, Helen D.; Reinhardt, Dieter P.; Anderson, Richard A.; Rodgers, Raymond J.

2011-01-01

Although not often discussed, the ovaries of women with polycystic ovary syndrome (PCOS) show all the hallmarks of increased TGF-β activity, with increased amounts of fibrous tissue and collagen in the ovarian capsule or tunica albuginea and ovarian stroma. Recent studies suggest that PCOS could have fetal origins. Genetic studies of PCOS have also found linkage with a microsatellite located in intron 55 of the extracellular matrix protein fibrillin 3. Fibrillins regulate TGF-β bioactivity in tissues by binding latent TGF-β binding proteins. We therefore examined expression of fibrillins 1–3, latent TGF-β binding proteins 1–4, and TGF-β 1–3 in bovine and human fetal ovaries at different stages of gestation and in adult ovaries. We also immunolocalized fibrillins 1 and 3. The results indicate that TGF-β pathways operate during ovarian fetal development, but most important, we show fibrillin 3 is present in the stromal compartments of fetal ovaries and is highly expressed at a critical stage early in developing human and bovine fetal ovaries when stroma is expanding and follicles are forming. These changes in expression of fibrillin 3 in the fetal ovary could lead to a predisposition to develop PCOS in later life.—Hatzirodos, N., Bayne, R. A., Irving-Rodgers, H. F., Hummitzsch, K., Sabatier, L., Lee, S., Bonner, W., Gibson, M. A., Rainey, W. E., Carr, B. R., Mason, H. D., Reinhardt, D. P., Anderson, R. A., Rodgers, R. J. Linkage of regulators of TGF-β activity in the fetal ovary to polycystic ovary syndrome. PMID:21411746

Integrin-linked kinase is required for TGF-β1 induction of dermal myofibroblast differentiation.

Science.gov (United States)

Vi, Linda; de Lasa, Cristina; DiGuglielmo, Gianni M; Dagnino, Lina

2011-03-01

Cutaneous repair after injury requires activation of resident dermal fibroblasts and their transition to myofibroblasts. The key stimuli for myofibroblast formation are activation of transforming growth factor-β (TGF-β) receptors and mechanotransduction mediated by integrins and associated proteins. We investigated the role of integrin-linked kinase (ILK) in TGF-β1 induction of dermal fibroblast transition to myofibroblasts. ILK-deficient fibroblasts treated with TGF-β1 exhibited attenuation of Smad 2 and 3 phosphorylation, accompanied by impaired transcriptional activation of Smad targets, such as α-smooth muscle actin. These alterations were not limited to Smad-associated TGF-β1 responses, as stimulation of noncanonical mitogen-activated protein kinase pathways by this growth factor was also diminished in the absence of ILK. ILK-deficient fibroblasts exhibited abnormalities in the actin cytoskeleton, and did not form supermature focal adhesions or contractile F-actin stress fibers, indicating a severe impairment in their capacity to differentiate into myofibroblasts. These defects extended to the inability of cells to contract extracellular matrices when embedded in collagen lattices. We conclude that ILK is necessary to transduce signals implicated in the transition of dermal fibroblasts to myofibroblasts originating from matrix substrates and TGF-β1.

Flash X-ray

International Nuclear Information System (INIS)

Sato, Eiichi

2003-01-01

Generation of quasi-monochromatic X-ray by production of weakly ionized line plasma (flash X-ray), high-speed imaging by the X-ray and high-contrast imaging by the characteristic X-ray absorption are described. The equipment for the X-ray is consisted from the high-voltage power supply and condenser, turbo molecular pump, and plasma X-ray tube. The tube has a long linear anticathode to produce the line plasma and flash X-ray at 20 kA current at maximum. X-ray spectrum is measured by the imaging plate equipped in the computed radiography system after diffracted by a LiF single crystal bender. Cu anticathode generates sharp peaks of K X-ray series. The tissue images are presented for vertebra, rabbit ear and heart, and dog heart by X-ray fluoroscopy with Ce anticathode. Generation of K-orbit characteristic X-ray with extremely low bremsstrahung is to be attempted for medical use. (N.I.)

Soluble TGF-β type II receptor gene therapy reduces TGF-β activity in irradiated lung tissue and protects lungs from radiation-induced injury

International Nuclear Information System (INIS)

Vujaskovic, Z.; Rabbani, Z.; Zhang, X.; Samulski, T.V.; Li, C.-Y.; Anscher, M.S.

2003-01-01

Full text: The objective was to determine whether administration of recombinant human adenoviral vector carrying soluble TGF-β1 type II receptor (TβR-II) gene reduces availability of active TGFβ1 and protects lung from radiation-induced injury. Female Fisher-344 rats were randomized into four groups to receive: 1) Control 2) Adenoviral green fluorescent protein vector (AdGFP) alone 3) Radiation (RT) + Adenoviral vector with TGF-β1 type II receptor gene (AdexTβR-II-Fc) 4) RT alone. Animals were irradiated to right hemithorax using a single dose of 30 Gy. The packaging and production of a recombinant adenovirus carrying the fused human TβR-II-IgG1 Fc gene was achieved by use of the AdEasy system. The treatment vector AdexTbR-II-Fc (1.5*1010 PFU) and control vector AdGFP (1*109 PFU) were injected i.v. 24 hrs after RT. Respiratory rate was measured as an index of pulmonary function weekly for 5 weeks post RT. Structural damage was scored histologically. Immunohistochemistry was performed to identify activated macrophages. ELISA was used to quantify active TGF-β1 in tissue homogenate. Western blot was used to determine TβR-II expression in plasma and lung tissue. Animals receiving treatment vector AdexTbR-II-Fc have elevated plasma levels of soluble TβR-II at 24 and 48 hours after injection. In the RT+AdexTbR-II-Fc group, there was a significant reduction in respiratory rate (p = 0.002) at four weeks after treatment compared to RT alone group. Histology revealed a significant reduction in lung structural damage in animals receiving gene therapy after RT vs RT alone (p=0.0013). There was also a decrease in the number of activated macrophage (p= 0.02) in RT+AdexTbR-II-Fc group vs RT alone. The tissue protein expression of active TGF-β1 was significantly reduced in rats receiving RT+AdexTbR-II-Fc treatment (p<0.05). This study shows the ability of adenovirus mediated soluble TβR-II gene therapy to reduce tissue levels of active TGF-β1 and ameliorate radiation

Pengaruh Lama Pemberian Diet Tinggi Kolesterol terhadap Kadar LDL dan TGF-Β Serum Tikus Putih (Rattus novergicus strain Wistar

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Biomechy Oktomalioputri

2016-01-01

to observe the effect of duration of giving  high-cholesterol diet on Low Density Lipoprotein and Transforming Growth Factor β levels white rats (Rattus novergicus Wistar strain. This study uses  post-test only control group design, carried out on male rats Rattus novergicus 3-4 months, weight 200-250 grams. The study sample consisted of 24 rats were divided into 4 groups: control group, group A, group B and group C. Except  the control group, the group of rats given a high-cholesterol diet in the form of goat fat 10%, 5% quail eggs for 10 days to group A, group B for 20 days and 30 days for group C. At the end of the experiment blood was taken and examined LDL and TGF-β levels. Results were analyzed using bivariate. The analysis is oneway Anova test. The results of research known to have effect of duration on giving high-cholesterol diet to increase serum LDL levels of rats with p = 0.01 (p<0.05. This is the same case with TGF-β, which there was effect of duration on giving high-diet cholesterol diet to decrease serum TGF-β levels of rats where p = 0.04 (p>0.05. This study concludes that there are effect of duration on giving high-cholesterol diet to levels of LDL and TGF-β white rats Rattus novergicus Wistar strain.Keywords:  high-cholesterol diet, LDL, TGF β

Numerical analyses of flashing jet structure and droplet size characteristics

International Nuclear Information System (INIS)

Duan Riqiang; Jiang Shengyao; Koshizuka, Seiichi; Oka, Yoshiaki; Yamaguchi, Akira; Takata, Takashi

2006-01-01

In this paper, flashing jets are numerically simulated using the MPS method. The boiling mode for flashing is identified as surface boiling mode, based on the postulation of jets from a short nozzle under high depressurization. The Homogeneous Non-equilibrium Relaxation Model (HRM) is used for calculating the evaporation rate of flashing. The numerical simulation results show that flashing jets comprise an inner intact core which is surrounded by two-phase droplet flow. The effect of degree of superheat on the jet topological geometry is investigated. With increasing degree of superheat, the topological shape of flashing jets evolves from cylindrical core for low degree of superheat to cone-shaped core for high degree of superheat, and meanwhile the extinction length comes to decrease and tends asymptotically constant as the injection temperature approaches the saturation temperature corresponding to the injection pressure. The analyses of the droplet size distribution engendered from primary breakup of flashing jets show that: two peaks exist for droplet size distribution at lower degree of superheat; however, merely one peak for higher degree of superheat. From droplet size distribution, it is revealed that the primary breakup mechanism of flashing jets can be attributed to dominant mechanical breakup mode plus enhancement via surface evaporation. (author)

49 CFR 234.253 - Flashing light units and lamp voltage.

Science.gov (United States)

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false Flashing light units and lamp voltage. 234.253... Maintenance, Inspection, and Testing Inspections and Tests § 234.253 Flashing light units and lamp voltage. (a... voltage shall be tested when installed and at least once every 12 months thereafter. (c) Each flashing...

Analysis of interaction between TGF and the myogenic response in renal blood flow autoregulation

DEFF Research Database (Denmark)

Feldberg, R; Colding-Jørgensen, M; Holstein-Rathlou, N H

1995-01-01

. The contribution of TGF to smooth muscle activity is assumed to be a linear function of the glomerular capillary pressure. The results show that the myogenic response plays an important role in renal blood flow autoregulation. Without a myogenic response, mechanisms such as TGF that are localized in the distal......The present study investigates the interaction between the tubuloglomerular feedback (TGF) response and the myogenic mechanism by use of a mathematical model. The two control mechanisms are implemented in a spatially distributed model of the rat renal juxtamedullary afferent arteriole. The model...

GSK3β attenuates TGF-β1 induced epithelial–mesenchymal transition and metabolic alterations in ARPE-19 cells

International Nuclear Information System (INIS)

Huang, Li; Zhang, Cheng; Su, Li; Song, Zhengyu

2017-01-01

While TGF-β1 is known to induce epithelial–mesenchymal transition (EMT), a major factor in the pathogenesis of proliferative vitreoretinopathy (PVR), in ARPE-19 cells. The molecular pathways involved in EMT formation have not yet to be fully characterized. In this study, we have found that TGF-β1-mediated induction of EMT in ARPE-19 cells varied in a dose- and time-dependent manner. Specifically, TGF-β1 inhibited GSK-3β by accelerating phosphorylation at ser9. GSK-3β inhibitor or knockdown of GSK-3β resulted in enhanced TGF-β1-mediated EMT, migration and collagen contraction in ARPE-19 cells, which were then abrogated by GSK-3β overexpression and PI3K/AKT inhibitor. Importantly, GSK-3β also mediated metabolic reprogramming in TGF-β1-treated cells. Our results indicate that GSK-3β plays a pivotal role in TGF-β1-mediated EMT in ARPE-19 cells. - Highlights: • GSK-3β mediates epithelial-mesenchymal transition in TGF-β1 treated ARPE-19 cells. • GSK-3β regulates cell migration and collagen contraction of ARPE-19 cells. • TGF-β1 induces extracellular metabolomic changes of ARPE-19 cells via a GSK-3β-dependent mechanism.

Fluorescence Lyman-Alpha Stratospheric Hygrometer (FLASH): application on meteorological balloons, long duration balloons and unmanned aerial vehicles.

Science.gov (United States)

Lykov, Alexey; Khaykin, Sergey; Yushkov, Vladimir; Efremov, Denis; Formanyuk, Ivan; Astakhov, Valeriy

The FLASH instrument is based on the fluorescent method, which uses H2O molecules photodissociation at a wavelength lambda=121.6 nm (Lalpha - hydrogen emission) followed by the measurement of the fluorescence of excited OH radicals. The source of Lyman-alpha radiation is a hydrogen discharge lamp while the detector of OH fluorescence at 308 -316 nm is a photomultiplier run in photon counting mode. The intensity of the fluorescent light as well as the instrument readings is directly proportional to the water vapor mixing ratio under stratospheric conditions with negligible oxygen absorption. Initially designed for rocket-borne application, FLASH has evolved into a light-weight balloon sonde (FLASH-B) for measurements in the upper troposphere and stratosphere on board meteorological and small plastic balloons. This configuration has been used in over 100 soundings at numerous tropical mid-latitude and polar locations within various international field campaigns. An airborne version of FLASH instrument is successfully utilized onboard stratospheric M55-Geophysica aircraft and tropospheric airborne laboratory YAK42-Roshydromet. The hygrometer was modified for application onboard stratospheric long-duration balloons (FLASH-LDB version). This version was successfully used onboard CNES super-pressure balloon launched from SSC Esrange in March 2007 and flown during 10 days. Special design for polar long duration balloon PoGOLite was created for testing work during polar day in June 2013. Installation and measurement peculiarities as well as observational results are presented. Observations of water vapour using FLASH-B instrument, being of high quality are rather costly as the payload recovery is often complicated and most of the time impossible. Following the goal to find a cost-efficient solution, FLASH was adapted for use onboard Unmanned Aerial Vehicles (UAV). This solution was only possible thanks to compactness and light-weight (0.5 kg) of FLASH instrument. The

Negative control of the HGF/c-MET pathway by TGF-β: a new look at the regulation of stemness in glioblastoma.

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Papa, Eleanna; Weller, Michael; Weiss, Tobias; Ventura, Elisa; Burghardt, Isabel; Szabó, Emese

2017-12-13

Multiple target inhibition has gained considerable interest in combating drug resistance in glioblastoma, however, understanding the molecular mechanisms of crosstalk between signaling pathways and predicting responses of cancer cells to targeted interventions has remained challenging. Despite the significant role attributed to transforming growth factor (TGF)-β family and hepatocyte growth factor (HGF)/c-MET signaling in glioblastoma pathogenesis, their functional interactions have not been well characterized. Using genetic and pharmacological approaches to stimulate or antagonize the TGF-β pathway in human glioma-initiating cells (GIC), we observed that TGF-β exerts an inhibitory effect on c-MET phosphorylation. Inhibition of either mitogen-activated protein kinase (MAPK)/ extracellular signal-regulated kinase (ERK) or phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB/AKT) signaling pathway attenuated this effect. A comparison of c-MET-driven and c-MET independent GIC models revealed that TGF-β inhibits stemness in GIC at least in part via its negative regulation of c-MET activity, suggesting that stem cell (SC) maintenance may be controlled by the balance between these two oncogenic pathways. Importantly, immunohistochemical analyses of human glioblastoma and ex vivo single-cell gene expression profiling of TGF-β and HGF confirm the negative interaction between both pathways. These novel insights into the crosstalk of two major pathogenic pathways in glioblastoma may explain some of the disappointing results when targeting either pathway alone in human glioblastoma patients and inform on potential future designs on targeted pharmacological or genetic intervention.

TGF-β Small Molecule Inhibitor SB431542 Reduces Rotator Cuff Muscle Fibrosis and Fatty Infiltration By Promoting Fibro/Adipogenic Progenitor Apoptosis.

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Michael R Davies

Full Text Available Rotator cuff tears represent a large burden of muscle-tendon injuries in our aging population. While small tears can be repaired surgically with good outcomes, critical size tears are marked by muscle atrophy, fibrosis, and fatty infiltration, which can lead to failed repair, frequent re-injury, and chronic disability. Previous animal studies have indicated that Transforming Growth Factor-β (TGF-β signaling may play an important role in the development of these muscle pathologies after injury. Here, we demonstrated that inhibition of TGF-β1 signaling with the small molecule inhibitor SB431542 in a mouse model of massive rotator cuff tear results in decreased fibrosis, fatty infiltration, and muscle weight loss. These observed phenotypic changes were accompanied by decreased fibrotic, adipogenic, and atrophy-related gene expression in the injured muscle of mice treated with SB431542. We further demonstrated that treatment with SB431542 reduces the number of fibro/adipogenic progenitor (FAP cells-an important cellular origin of rotator cuff muscle fibrosis and fatty infiltration, in injured muscle by promoting apoptosis of FAPs. Together, these data indicate that the TGF-β pathway is a critical regulator of the degenerative muscle changes seen after massive rotator cuff tears. TGF-β promotes rotator cuff muscle fibrosis and fatty infiltration by preventing FAP apoptosis. TGF-β regulated FAP apoptosis may serve as an important target pathway in the future development of novel therapeutics to improve muscle outcomes following rotator cuff tear.

Suppressed Gastric Mucosal TGF-β1 Increases Susceptibility to H. pylori-Induced Gastric Inflammation and Ulceration: A Stupid Host Defense Response

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Jo, Yunjeong; Han, Sang Uk; Kim, Yoon Jae; Kim, Ju Hyeon; Kim, Shin Tae; Kim, Seong-Jin

2010-01-01

Background/Aims Loss of transforming growth factor β1 (TGF-β1) exhibits a similar pathology to that seen in a subset of individuals infected with Helicobacter pylori, including propagated gastric inflammation, oxidative stress, and autoimmune features. We thus hypothesized that gastric mucosal TGF-β1 levels could be used to determine the outcome after H. pylori infection. Methods Northern blot for the TGF-β1 transcript, staining of TGF-β1 expression, luciferase reporter assay, and enzyme-linked immunosorbent assay for TGF-β1 levels were performed at different times after H. pylori infection. Results The TGF-β1 level was markedly lower in patients with H. pylori-induced gastritis than in patients with a similar degree of gastritis induced by nonsteroidal anti-inflammatory drugs. There was a significant negative correlation between the severity of inflammation and gastric mucosal TGF-β1 levels. SNU-16 cells showing intact TGF-β signaling exhibited a marked decrease in TGF-β1 expression, whereas SNU-638 cells defective in TGF-β signaling exhibited no such decrease after H. pylori infection. The decreased expressions of TGF-β1 in SNU-16 cells recovered to normal after 24 hr of H. pylori infection, but lasted very spatial times, suggesting that attenuated expression of TGF-β1 is a host defense mechanism to avoid attachment of H. pylori. Conclusions H. pylori infection was associated with depressed gastric mucosal TGF-β1 for up to 24 hr, but this apparent strategy for rescuing cells from H. pylori attachment exacerbated the gastric inflammation. PMID:20479912

Suppressed Gastric Mucosal TGF-beta1 Increases Susceptibility to H. pylori-Induced Gastric Inflammation and Ulceration: A Stupid Host Defense Response.

Science.gov (United States)

Jo, Yunjeong; Han, Sang Uk; Kim, Yoon Jae; Kim, Ju Hyeon; Kim, Shin Tae; Kim, Seong-Jin; Hahm, Ki-Baik

2010-03-01

Loss of transforming growth factor beta1 (TGF-beta1) exhibits a similar pathology to that seen in a subset of individuals infected with Helicobacter pylori, including propagated gastric inflammation, oxidative stress, and autoimmune features. We thus hypothesized that gastric mucosal TGF-beta1 levels could be used to determine the outcome after H. pylori infection. Northern blot for the TGF-beta1 transcript, staining of TGF-beta1 expression, luciferase reporter assay, and enzyme-linked immunosorbent assay for TGF-beta1 levels were performed at different times after H. pylori infection. The TGF-beta1 level was markedly lower in patients with H. pylori-induced gastritis than in patients with a similar degree of gastritis induced by nonsteroidal anti-inflammatory drugs. There was a significant negative correlation between the severity of inflammation and gastric mucosal TGF-beta1 levels. SNU-16 cells showing intact TGF-beta signaling exhibited a marked decrease in TGF-beta1 expression, whereas SNU-638 cells defective in TGF-beta signaling exhibited no such decrease after H. pylori infection. The decreased expressions of TGF-beta1 in SNU-16 cells recovered to normal after 24 hr of H. pylori infection, but lasted very spatial times, suggesting that attenuated expression of TGF-beta1 is a host defense mechanism to avoid attachment of H. pylori. H. pylori infection was associated with depressed gastric mucosal TGF-beta1 for up to 24 hr, but this apparent strategy for rescuing cells from H. pylori attachment exacerbated the gastric inflammation.

Freeware eLearning Flash-ECG for learning electrocardiography.

Science.gov (United States)

Romanov, Kalle; Kuusi, Timo

2009-06-01

Electrocardiographic (ECG) analysis can be taught in eLearning programmes with suitable software that permits the effective use of basic tools such as a ruler and a magnifier, required for measurements. The Flash-ECG (Research & Development Unit for Medical Education, University of Helsinki, Finland) was developed to enable teachers and students to use scanned and archived ECGs on computer screens and classroom projectors. The software requires only a standard web browser with a Flash plug-in and can be integrated with learning environments (Blackboard/WebCT, Moodle). The Flash-ECG is freeware and is available to medical teachers worldwide.

Nitric oxide and TGF-β1 inhibit HNF-4α function in HEPG2 cells

International Nuclear Information System (INIS)

Lucas, Susana de; Lopez-Alcorocho, Juan Manuel; Bartolome, Javier; Carreno, Vicente

2004-01-01

This study analyzes if the profibrogenic factors nitric oxide and transforming growth factor-β1 (TGF-β1) affect hepatocyte nuclear factor-4α (HNF-4α) function. For this purpose, HepG2 cells were treated with TGF-β1 or with a nitric oxide donor to determine mRNA levels of coagulation factor VII and HNF-4α. Treatment effect on factor VII gene promoter was assessed by chloramphenicol acetyl-transferase assays in cells transfected with the pFVII-CAT plasmid. HNF-4α binding and protein levels were determined by gel shift assays and Western blot. TGF-β1 and nitric oxide downregulated factor VII mRNA levels by inhibiting its gene promoter activity. This inhibition is caused by a decrease in the DNA binding of HNF-4α. TGF-β1 induces degradation of HNF-4α in the proteasome while nitric oxide provokes nitrosylation of cysteine residues in this factor. TGF-β1 and nitric oxide inhibit HNF-4α activity. These findings may explain the loss of liver functions that occurs during fibrosis progression

TGF-β Suppression of HBV RNA through AID-Dependent Recruitment of an RNA Exosome Complex

Science.gov (United States)

Kitamura, Kouichi; Wang, Zhe; Chowdhury, Sajeda; Monjurul, Ahasan Md; Wakae, Kousho; Koura, Miki; Shimadu, Miyuki; Kinoshita, Kazuo; Muramatsu, Masamichi

2015-01-01

Transforming growth factor (TGF)-β inhibits hepatitis B virus (HBV) replication although the intracellular effectors involved are not determined. Here, we report that reduction of HBV transcripts by TGF-β is dependent on AID expression, which significantly decreases both HBV transcripts and viral DNA, resulting in inhibition of viral replication. Immunoprecipitation reveals that AID physically associates with viral P protein that binds to specific virus RNA sequence called epsilon. AID also binds to an RNA degradation complex (RNA exosome proteins), indicating that AID, RNA exosome, and P protein form an RNP complex. Suppression of HBV transcripts by TGF-β was abrogated by depletion of either AID or RNA exosome components, suggesting that AID and the RNA exosome involve in TGF-β mediated suppression of HBV RNA. Moreover, AID-mediated HBV reduction does not occur when P protein is disrupted or when viral transcription is inhibited. These results suggest that induced expression of AID by TGF-β causes recruitment of the RNA exosome to viral RNP complex and the RNA exosome degrades HBV RNA in a transcription-coupled manner. PMID:25836330

TGF-β regulates DNA methyltransferase expression in prostate cancer, correlates with aggressive capabilities, and predicts disease recurrence.

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Qiang Zhang

Full Text Available DNA methyltransferase (DNMT is one of the major factors mediating the methylation of cancer related genes such as TGF-β receptors (TβRs. This in turn may result in a loss of sensitivity to physiologic levels of TGF-β in aggressive prostate cancer (CaP. The specific mechanisms of DNMT's role in CaP remain undetermined. In this study, we describe the mechanism of TGF-β-mediated DNMT in CaP and its association with clinical outcomes following radical prostatectomy.We used human CaP cell lines with varying degrees of invasive capability to describe how TGF-β mediates the expression of DNMT in CaP, and its effects on methylation status of TGF-β receptors and the invasive capability of CaP in vitro and in vivo. Furthermore, we determined the association between DNMT expression and clinical outcome after radical prostatectomy. We found that more aggressive CaP cells had significantly higher TGF-β levels, increased expression of DNMT, but reduced TβRs when compared to benign prostate cells and less aggressive prostate cancer cells. Blockade of TGF-β signaling or ERK activation (p-ERK was associated with a dramatic decrease in the expression of DNMT, which results in a coincident increase in the expression of TβRs. Blockade of either TGF-β signaling or DNMT dramatically decreased the invasive capabilities of CaP. Inhibition of TGF-β in an TRAMP-C2 CaP model in C57BL/6 mice using 1D11 was associated with downregulation of DNMTs and p-ERK and impairment in tumor growth. Finally, independent of Gleason grade, increased DNMT1 expression was associated with biochemical recurrence following surgical treatment for prostate cancer.Our findings demonstrate that CaP derived TGF-β may induce the expression of DNMTs in CaP which is associated with methylation of its receptors and the aggressive potential of CaP. In addition, DNMTs is an independent predictor for disease recurrence after prostatectomy, and may have clinical implications for Ca

Transforming growth factor β2 (TGF-β2 in pathogenesis of oral submucous fibrosis: An immunohistochemical study

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Venkatesh V Kamath

2014-01-01

Full Text Available Background and Objectives: Oral Submucous Fibrosis (OSF is a potentially malignant oral disorder causing fibrosis of the oral mucosa. Commonly associated with the habit of chewing areca nut in its raw or refined forms, the progressive fibrosis causes intense debility and probable malignant transformation. Arecoline, flavinoids and tannins in the areca nut may activate pro-fibrotic cytokines like transforming growth factor beta (TGF-β leading to fibrosis. TGF-β and its isoforms probably represent the major pathway in the deposition of collagen fibers in this condition. Very little is known of the role of TGF-β2, as compared withTGF-β1, in OSF. The present study aims to evaluate TGF-β2 immunohistochemically in OSF with a view to understanding its role in the pathogenesis. Materials and Methods: TGF-β2 antibody was detected immunohistochemically on archival paraffin sections of 70 cases of various grades of OSF, 10 cases of normal oral mucosa and five cases of scar tissue. The presence and distribution of the antibody was noted and a quantification of the positive areas was also done using image analyses software and correlated in proportion to the rest of the tissue. Results: Expression of TGF-β2 was more in all grades of OSF when compared with that of normal oral mucosa but less than that expressed in scar tissue. The antibody was detected in epithelium, around the blood vessels, in areas of inflammatory infiltrate, fibroblasts and in muscles. The intensity and proportion of expression paralleled increasing grades of OSF. There was increased expression of the antibody in the epithelium, which is probably the source, but no correlation to epithelial changes (hyperplasia, atrophy or dysplasia was noted. Conclusion: TGF-β2 is a prominent cytokine in the TGF-β induced pathway of fibrosis but probably plays a contributory role to the main isoform TGF-β1. Its role as a marker of malignant transformation, as seen in other systemic malignant

The Ground Flash Fraction Retrieval Algorithm Employing Differential Evolution: Simulations and Applications

Science.gov (United States)

Koshak, William; Solakiewicz, Richard

2012-01-01

The ability to estimate the fraction of ground flashes in a set of flashes observed by a satellite lightning imager, such as the future GOES-R Geostationary Lightning Mapper (GLM), would likely improve operational and scientific applications (e.g., severe weather warnings, lightning nitrogen oxides studies, and global electric circuit analyses). A Bayesian inversion method, called the Ground Flash Fraction Retrieval Algorithm (GoFFRA), was recently developed for estimating the ground flash fraction. The method uses a constrained mixed exponential distribution model to describe a particular lightning optical measurement called the Maximum Group Area (MGA). To obtain the optimum model parameters (one of which is the desired ground flash fraction), a scalar function must be minimized. This minimization is difficult because of two problems: (1) Label Switching (LS), and (2) Parameter Identity Theft (PIT). The LS problem is well known in the literature on mixed exponential distributions, and the PIT problem was discovered in this study. Each problem occurs when one allows the numerical minimizer to freely roam through the parameter search space; this allows certain solution parameters to interchange roles which leads to fundamental ambiguities, and solution error. A major accomplishment of this study is that we have employed a state-of-the-art genetic-based global optimization algorithm called Differential Evolution (DE) that constrains the parameter search in such a way as to remove both the LS and PIT problems. To test the performance of the GoFFRA when DE is employed, we applied it to analyze simulated MGA datasets that we generated from known mixed exponential distributions. Moreover, we evaluated the GoFFRA/DE method by applying it to analyze actual MGAs derived from low-Earth orbiting lightning imaging sensor data; the actual MGA data were classified as either ground or cloud flash MGAs using National Lightning Detection Network[TM] (NLDN) data. Solution error

A Scalable and Highly Configurable Cache-Aware Hybrid Flash Translation Layer

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Jalil Boukhobza

2014-03-01

Full Text Available This paper presents a cache-aware configurable hybrid flash translation layer (FTL, named CACH-FTL. It was designed based on the observation that most state-of­­-the-art flash-specific cache systems above FTLs flush groups of pages belonging to the same data block. CACH-FTL relies on this characteristic to optimize flash write operations placement, as large groups of pages are flushed to a block-mapped region, named BMR, whereas small groups are buffered into a page-mapped region, named PMR. Page group placement is based on a configurable threshold defining the limit under which it is more cost-effective to use page mapping (PMR and wait for grouping more pages before flushing to the BMR. CACH-FTL is scalable in terms of mapping table size and flexible in terms of Input/Output (I/O workload support. CACH-FTL performs very well, as the performance difference with the ideal page-mapped FTL is less than 15% in most cases and has a mean of 4% for the best CACH-FTL configurations, while using at least 78% less memory for table mapping storage on RAM.

TGF-β2 initiates autophagy via Smad and non-Smad pathway to promote glioma cells’ invasion

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Chao Zhang

2017-11-01

Full Text Available Abstract Background Glioblastoma multiforme (GBM is characterized by lethal aggressiveness and patients with GBM are in urgent need for new therapeutic avenues to improve quality of life. Current studies on tumor invasion focused on roles of cytokines in tumor microenvironment and numerous evidence suggests that TGF-β2 is abundant in glioma microenvironment and vital for glioma invasion. Autopagy is also emerging as a critical factor in aggressive behaviors of cancer cells; however, the relationship between TGF-β2 and autophagy in glioma has been poorly understood. Methods U251, T98 and U87 GBM cell lines as well as GBM cells from a primary human specimen were used in vitro and in vivo to evaluate the effect of TGF-β2 on autophagy. Western blot, qPCR, immunofluorescence and transmission-electron microscope were used to detect target molecular expression. Lentivirus and siRNA vehicle were introduced to establish cell lines, as well as mitotracker and seahorse experiment to study the metabolic process in glioma. Preclinical therapeutic efficacy was evaluated in orthotopic xenograft mouse models. Results Here we demonstrated that TGF-β2 activated autophagy in human glioma cell lines and knockdown of Smad2 or inhibition of c-Jun NH2-terminal kinase, attenuated TGF-β2-induced autophagy. TGF-β2-induced autophagy is important for glioma invasion due to the alteration of epithelial-mesenchymal transition and metabolism conversion, particularly influencing mitochondria trafficking and membrane potential (△Ψm. Autopaghy also initiated a feedback on TGF-β2 in glioma by keeping its autocrine loop and affecting Smad2/3/7 expression. A xenograft model provided additional confirmation on combination of TGF-β inhibitor (Galunisertib and autophagy inhibitor (CQ to better “turn off” tumor growth. Conclusion Our findings elucidated a potential mechanism of autophagy-associated glioma invasion that TGF-β2 could initiate autophagy via Smad and non

TGF-ß Regulates Cathepsin Activation during Normal and Pathogenic Development.

Science.gov (United States)

Flanagan-Steet, Heather; Christian, Courtney; Lu, Po-Nien; Aarnio-Peterson, Megan; Sanman, Laura; Archer-Hartmann, Stephanie; Azadi, Parastoo; Bogyo, Matthew; Steet, Richard A

2018-03-13

Cysteine cathepsins play roles during development and disease beyond their function in lysosomal protein turnover. Here, we leverage a fluorescent activity-based probe (ABP), BMV109, to track cysteine cathepsins in normal and diseased zebrafish embryos. Using this probe in a model of mucolipidosis II, we show that loss of carbohydrate-dependent lysosomal sorting alters the activity of several cathepsin proteases. The data support a pathogenic mechanism where TGF-ß signals enhance the proteolytic processing of pro-Ctsk by modulating the expression of chondroitin 4-sulfate (C4-S). In MLII, elevated C4-S corresponds with TGF-ß-mediated increases in chst11 expression. Inhibiting chst11 impairs the proteolytic activation of Ctsk and alleviates the MLII phenotypes. These findings uncover a regulatory loop between TGF-ß signaling and Ctsk activation that is altered in the context of lysosomal disease. This work highlights the power of ABPs to identify mechanisms underlying pathogenic development in living animals. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Simple flash evaporator for making thin films of compounds

Energy Technology Data Exchange (ETDEWEB)

Hemanadhan, M.; Bapanayya, Ch.; Agarwal, S. C. [Department of Physics, Indian Institute of Technology, Kanpur 208016 (India)

2010-07-15

A simple and compact arrangement for flash evaporation is described. It uses a cell phone vibrator for powder dispensing that can be incorporated into a vacuum deposition chamber without any major alterations. The performance of the flash evaporation system is checked by making thin films of the optical memory chalcogenide glass Ge{sub 2}Sb{sub 2}Te{sub 5} (GST). Energy dispersive x-ray analysis shows that the flash evaporation preserves the stoichiometry in thin films.

Heavy ions light flashes and brain functions: recent observations at accelerators and in spaceflight

Energy Technology Data Exchange (ETDEWEB)

Narici, L [Department of Physics, University of Rome Tor Vergata, and INFN Roma Tor Vergata, Via della Ricerca Scientifica 1, 00133 Rome (Italy)], E-mail: livio.narici@roma2.infn.it

2008-07-15

Interactions between ionizing radiation in space and brain functions, and the related risk assessments, are among the major concerns when programming long permanence in space, especially when outside the protective shield of the Earth's magnetosphere. The light flashes (LF) observed by astronauts in space, mostly when dark adapted, are an example of these interactions; investigations in space and on the ground showed that these effects can originate with the action of ionizing radiation in the eye. Recent findings from ALTEA, an interdisciplinary and multiapproach program devoted to the study of different aspects of the radiation-brain functions interaction, are presented in this paper. These include: (i) study of radiation passing through the astronauts' eyes in the International Space Station ({approx}20 ions min{sup -1}, excluding H and fast and very slow He), measured in conjunction with reporting of the perception of LF; (ii) preliminary electrophysiological evidence of these events in astronauts and in patients during heavy ion therapy; and (iii) in vitro results showing the radiation driven activation of rhodopsin at the start of the phototransduction cascade in the process of vision. These results are in agreement with our previous work on mice. A brief but complete summary of the earlier works is also reported to permit a discussion of the results.

The DAF-7/TGF-β signaling pathway regulates abundance of the C. elegans glutamate receptor GLR-1

Science.gov (United States)

McGehee, Annette M.; Moss, Benjamin J.; Juo, Peter

2015-01-01

Transforming growth factor-β (TGF-β) family signaling pathways have roles in both neuronal development and the regulation of synaptic function. Here we identify a novel role for the C. elegans DAF-7/TGF-β signaling pathway in the regulation of the AMPA-type glutamate receptor GLR-1. We found that the abundance of GLR-1 increases at synapses in the ventral nerve cord (VNC) of animals with loss-of-function mutations in multiple DAF-7/TGF-β pathway components including the TGF-β ligand DAF-7, the type I receptor DAF-1, and the Smads DAF-8 and DAF-14. The GLR-1 defect can be rescued by expression of daf-8 specifically in glr-1-expressing interneurons. The effect on GLR-1 was specific for the DAF-7 pathway because mutations in the DBL-1/TGF-β family pathway did not increase GLR-1 levels in the VNC. Immunoblot analysis indicates that total levels of GLR-1 protein are increased in neurons of DAF-7/TGF-β pathway mutants. The increased abundance of GLR-1 in the VNC of daf-7 pathway mutants is dependent on the transcriptional regulator DAF-3/Smad suggesting that DAF-3-dependent transcription controls GLR-1 levels. Furthermore, we found that glr-1 transcription is increased in daf-7 mutants based on a glr-1 transcriptional reporter. Together these results suggest that the DAF-7/TGF-β signaling pathway functions in neurons and negatively regulates the abundance of GLR-1, in part, by controlling transcription of the receptor itself. Finally, DAF-7/TGF-β pathway mutants exhibit changes in spontaneous locomotion that are dependent on endogenous GLR-1 and consistent with increased glutamatergic signaling. These results reveal a novel mechanism by which TGF-β signaling functions in the nervous system to regulate behavior. PMID:26054666