Simultaneous chromatic and luminance human electroretinogram responses.

Science.gov (United States)

Parry, Neil R A; Murray, Ian J; Panorgias, Athanasios; McKeefry, Declan J; Lee, Barry B; Kremers, Jan

2012-07-01

The parallel processing of information forms an important organisational principle of the primate visual system. Here we describe experiments which use a novel chromatic–achromatic temporal compound stimulus to simultaneously identify colour and luminance specific signals in the human electroretinogram (ERG). Luminance and chromatic components are separated in the stimulus; the luminance modulation has twice the temporal frequency of the chromatic modulation. ERGs were recorded from four trichromatic and two dichromatic subjects (1 deuteranope and 1 protanope). At isoluminance, the fundamental (first harmonic) response was elicited by the chromatic component in the stimulus. The trichromatic ERGs possessed low-pass temporal tuning characteristics, reflecting the activity of parvocellular post-receptoral mechanisms. There was very little first harmonic response in the dichromats' ERGs. The second harmonic response was elicited by the luminance modulation in the compound stimulus and showed, in all subjects, band-pass temporal tuning characteristic of magnocellular activity. Thus it is possible to concurrently elicit ERG responses from the human retina which reflect processing in both chromatic and luminance pathways. As well as providing a clear demonstration of the parallel nature of chromatic and luminance processing in the human retina, the differences that exist between ERGs from trichromatic and dichromatic subjects point to the existence of interactions between afferent post-receptoral pathways that are in operation from the earliest stages of visual processing.

Comparison of clinical outcomes between luminal invasive ductal carcinoma and luminal invasive lobular carcinoma.

Science.gov (United States)

Adachi, Yayoi; Ishiguro, Junko; Kotani, Haruru; Hisada, Tomoka; Ichikawa, Mari; Gondo, Naomi; Yoshimura, Akiyo; Kondo, Naoto; Hattori, Masaya; Sawaki, Masataka; Fujita, Takashi; Kikumori, Toyone; Yatabe, Yasushi; Kodera, Yasuhiro; Iwata, Hiroji

2016-03-25

The pathological and clinical features of invasive lobular carcinoma (ILC) differ from those of invasive ductal carcinoma (IDC). Several studies have indicated that patients with ILC have a better prognosis than those with ductal carcinoma. However, no previous study has considered the molecular subtypes and histological subtypes of ILC. We compared prognosis between IDC and classical, luminal type ILC and developed prognostic factors for early breast cancer patients with classical luminal ILC. Four thousand one hundred ten breast cancer patients were treated at the Aichi Cancer Center Hospital from 2003 to 2012. We identified 1,661 cases with luminal IDC and 105 cases with luminal classical ILC. We examined baseline characteristics, clinical outcomes, and prognostic factors of luminal ILC. The prognosis of luminal ILC was significantly worse than that of luminal IDC. The rates of 5-year disease free survival (DFS) were 91.9% and 88.4% for patients with luminal IDC and luminal ILC, respectively (P = 0.008). The rates of 5-year overall survival (OS) were 97.6% and 93.1% for patients with luminal IDC and luminal ILC respectively (P = 0.030). Although we analyzed prognosis according to stratification by tumor size, luminal ILC tended to have worse DFS than luminal IDC in the large tumor group. In addition, although our analysis was performed according to matching lymph node status, luminal ILC had a significantly worse DFS and OS than luminal IDC in node-positive patients. Survival curves showed that the prognosis for ILC became worse than IDC over time. Multivariate analysis showed that ILC was an important factor related to higher risk of recurrence of luminal type breast cancer, even when tumor size, lymph node status and histological grade were considered. Luminal ILC had worse outcomes than luminal IDC. Consequently, different treatment approaches should be used for luminal ILC than for luminal IDC.

Signaling Network Assessment of Mutations and Copy Number Variations Predict Breast Cancer Subtype-Specific Drug Targets

Directory of Open Access Journals (Sweden)

Naif Zaman

2013-10-01

Full Text Available Individual cancer cells carry a bewildering number of distinct genomic alterations (e.g., copy number variations and mutations, making it a challenge to uncover genomic-driven mechanisms governing tumorigenesis. Here, we performed exome sequencing on several breast cancer cell lines that represent two subtypes, luminal and basal. We integrated these sequencing data and functional RNAi screening data (for the identification of genes that are essential for cell proliferation and survival onto a human signaling network. Two subtype-specific networks that potentially represent core-signaling mechanisms underlying tumorigenesis were identified. Within both networks, we found that genes were differentially affected in different cell lines; i.e., in some cell lines a gene was identified through RNAi screening, whereas in others it was genomically altered. Interestingly, we found that highly connected network genes could be used to correctly classify breast tumors into subtypes on the basis of genomic alterations. Further, the networks effectively predicted subtype-specific drug targets, which were experimentally validated.

Comparison of clinical outcomes between luminal invasive ductal carcinoma and luminal invasive lobular carcinoma

International Nuclear Information System (INIS)

Adachi, Yayoi; Ishiguro, Junko; Kotani, Haruru; Hisada, Tomoka; Ichikawa, Mari; Gondo, Naomi; Yoshimura, Akiyo; Kondo, Naoto; Hattori, Masaya; Sawaki, Masataka; Fujita, Takashi; Kikumori, Toyone; Yatabe, Yasushi; Kodera, Yasuhiro; Iwata, Hiroji

2016-01-01

The pathological and clinical features of invasive lobular carcinoma (ILC) differ from those of invasive ductal carcinoma (IDC). Several studies have indicated that patients with ILC have a better prognosis than those with ductal carcinoma. However, no previous study has considered the molecular subtypes and histological subtypes of ILC. We compared prognosis between IDC and classical, luminal type ILC and developed prognostic factors for early breast cancer patients with classical luminal ILC. Four thousand one hundred ten breast cancer patients were treated at the Aichi Cancer Center Hospital from 2003 to 2012. We identified 1,661 cases with luminal IDC and 105 cases with luminal classical ILC. We examined baseline characteristics, clinical outcomes, and prognostic factors of luminal ILC. The prognosis of luminal ILC was significantly worse than that of luminal IDC. The rates of 5-year disease free survival (DFS) were 91.9 % and 88.4 % for patients with luminal IDC and luminal ILC, respectively (P = 0.008). The rates of 5-year overall survival (OS) were 97.6 % and 93.1 % for patients with luminal IDC and luminal ILC respectively (P = 0.030). Although we analyzed prognosis according to stratification by tumor size, luminal ILC tended to have worse DFS than luminal IDC in the large tumor group. In addition, although our analysis was performed according to matching lymph node status, luminal ILC had a significantly worse DFS and OS than luminal IDC in node-positive patients. Survival curves showed that the prognosis for ILC became worse than IDC over time. Multivariate analysis showed that ILC was an important factor related to higher risk of recurrence of luminal type breast cancer, even when tumor size, lymph node status and histological grade were considered. Luminal ILC had worse outcomes than luminal IDC. Consequently, different treatment approaches should be used for luminal ILC than for luminal IDC. The online version of this article (doi:10.1186/s12885

A Blind Pilot: Who is a Super-Luminal Observer?

Directory of Open Access Journals (Sweden)

Rabounski D.

2008-04-01

Full Text Available This paper discusses the nature of a hypothetical super-luminal observer who, as well as a real (sub-light speed observer, perceives the world by light waves. This consideration is due to that fact that the theory of relativity permits different frames of reference, including light-like and super-luminal reference frames. In analogy with a blind pilot on board a supersonic jet aeroplane (or missile, perceived by blind people, it is concluded that the light barrier is observed in the framework of only the light signal exchange experiment.

Development and construction of a programmable generator of luminous impulses

International Nuclear Information System (INIS)

Sahuc, P.

1989-01-01

The design and construction of an impulse generator, for light waves, designed to control the characteristics of a scintillator. In these detectors, a particle gives rise to the emission of a luminous signal, which must be transformed in an electrical signal. In the present work, photomultipliers are used as luminous-electrical signal converters. The principles of operation of a scintillator, of a scintillator connected with a photodiode, and of a scintillator connected with a photomultiplier are reviewed. The analysis of the performance and of the possibilies offered by the usual generators of light, show that more suitable solutions are required. The characteristics of the electroluminescent diodes, their performances, concerning light emission and power, are investigated. The principles, the operating conditions and the performances of a generator of light, applying electroluminescent diodes, are examined. The construction and the results obtained with a prototype are presented [fr

Luminal epithelial cells within the mammary gland can produce basal cells upon oncogenic stress.

Science.gov (United States)

Hein, S M; Haricharan, S; Johnston, A N; Toneff, M J; Reddy, J P; Dong, J; Bu, W; Li, Y

2016-03-17

In the normal mammary gland, the basal epithelium is known to be bipotent and can generate either basal or luminal cells, whereas the luminal epithelium has not been demonstrated to contribute to the basal compartment in an intact and normally developed mammary gland. It is not clear whether cellular heterogeneity within a breast tumor results from transformation of bipotent basal cells or from transformation and subsequent basal conversion of the more differentiated luminal cells. Here we used a retroviral vector to express an oncogene specifically in a small number of the mammary luminal epithelial cells and tested their potential to produce basal cells during tumorigenesis. This in-vivo lineage-tracing work demonstrates that luminal cells are capable of producing basal cells on activation of either polyoma middle T antigen or ErbB2 signaling. These findings reveal the plasticity of the luminal compartment during tumorigenesis and provide an explanation for cellular heterogeneity within a cancer.

Research on the calibration methods of the luminance parameter of radiation luminance meters

Science.gov (United States)

Cheng, Weihai; Huang, Biyong; Lin, Fangsheng; Li, Tiecheng; Yin, Dejin; Lai, Lei

2017-10-01

This paper introduces standard diffusion reflection white plate method and integrating sphere standard luminance source method to calibrate the luminance parameter. The paper compares the effects of calibration results by using these two methods through principle analysis and experimental verification. After using two methods to calibrate the same radiation luminance meter, the data obtained verifies the testing results of the two methods are both reliable. The results show that the display value using standard white plate method has fewer errors and better reproducibility. However, standard luminance source method is more convenient and suitable for on-site calibration. Moreover, standard luminance source method has wider range and can test the linear performance of the instruments.

Psychophysical and physiological responses to gratings with luminance and chromatic components of different spatial frequencies.

Science.gov (United States)

Cooper, Bonnie; Sun, Hao; Lee, Barry B

2012-02-01

Gratings that contain luminance and chromatic components of different spatial frequencies were used to study the segregation of signals in luminance and chromatic pathways. Psychophysical detection and discrimination thresholds to these compound gratings, with luminance and chromatic components of the one either half or double the spatial frequency of the other, were measured in human observers. Spatial frequency tuning curves for detection of compound gratings followed the envelope of those for luminance and chromatic gratings. Different grating types were discriminable at detection threshold. Fourier analysis of physiological responses of macaque retinal ganglion cells to compound waveforms showed chromatic information to be restricted to the parvocellular pathway and luminance information to the magnocellular pathway. Taken together, the human psychophysical and macaque physiological data support the strict segregation of luminance and chromatic information in independent channels, with the magnocellular and parvocellular pathways, respectively, serving as likely the physiological substrates. © 2012 Optical Society of America

Spatiotemporal Characteristics for the Depth from Luminance Contrast

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Kazuya Matsubara

2011-05-01

Full Text Available Images with higher luminance contrast tend to be perceived closer in depth. To investigate a spatiotemporal characteristic of this effect, we evaluated subjective depth of a test stimulus with various spatial and temporal frequencies. For the purpose, the depth of a reference stimulus was matched to that of the test stimulus by changing the binocular disparity. The results showed that the test stimulus was perceived closer with higher luminance contrast for all conditions. Contrast efficiency was obtained from the contrast that provided the subjective depth for each spatiotemporal frequency. The shape of the contrast efficiency function was spatially low-pass and temporally band-pass. This characteristic is different from the one measure for a detection task. This suggests that only subset of contrast signals are used for depth from contrast.

P1-5: Effect of Luminance Contrast on the Color Selective Responses in the Inferior Temporal Cortex Neurons of the Macaque Monkey

Directory of Open Access Journals (Sweden)

Tomoyuki Namima

2012-10-01

Full Text Available Although the relationship between color signal and luminance signal is an important problem in visual perception, relatively little is known about how the luminance contrast affects the responses of color selective neurons in the visual cortex. In this study, we examined this problem in the inferior temporal (IT of the awake monkey performing a visual fixation task. Single neuron activities were recorded from the anterior and posterior color selective regions in IT cortex (AITC and PITC identified in previous studies where color selective neurons are accumulated. Color stimuli consisted of 28 stimuli that evenly distribute across the gamut of the CRT display defined on the CIE- xychromaticity diagram at two different luminance levels (5 cd/m 2or 20 cd/m 2 and 2 stimuli at white points. The background was maintained at 10 cd/m 2gray. We found that the effect of luminance contrast on the color selectivity was markedly different between AITC and PITC. When we examined the correlation between the responses to the bright stimuli and those to the dark stimuli with the same chromaticity coordinates, most AITC neurons exhibited high correlation whereas many PITC neurons showed no correlation or only weak correlation. In PITC, the effect was specifically large for neutral colors (white, gray, black and for colors with low saturation. These results indicate that the effect of luminance contrast on the color selective responses differs across different areas and suggest that the separation between color signal and luminance signal involves a higher stage of the cortical color processing.

The ER stress sensor PERK luminal domain functions as a molecular chaperone to interact with misfolded proteins

Energy Technology Data Exchange (ETDEWEB)

Wang, Peng; Li, Jingzhi; Sha, Bingdong

2016-11-29

PERK is one of the major sensor proteins which can detect the protein-folding imbalance generated by endoplasmic reticulum (ER) stress. It remains unclear how the sensor protein PERK is activated by ER stress. It has been demonstrated that the PERK luminal domain can recognize and selectively interact with misfolded proteins but not native proteins. Moreover, the PERK luminal domain may function as a molecular chaperone to directly bind to and suppress the aggregation of a number of misfolded model proteins. The data strongly support the hypothesis that the PERK luminal domain can interact directly with misfolded proteins to induce ER stress signaling. To illustrate the mechanism by which the PERK luminal domain interacts with misfolded proteins, the crystal structure of the human PERK luminal domain was determined to 3.2 Å resolution. Two dimers of the PERK luminal domain constitute a tetramer in the asymmetric unit. Superimposition of the PERK luminal domain molecules indicated that the β-sandwich domain could adopt multiple conformations. It is hypothesized that the PERK luminal domain may utilize its flexible β-sandwich domain to recognize and interact with a broad range of misfolded proteins.

Study on the Influence Factors of the Luminous Intensity of the Long Afterglow Luminous Paints

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Zhao Su

2016-01-01

Full Text Available In order to extend the time afterglow luminous powder, enhancement the brightness of luminous paint, this study explore affect long afterglow energy storage luminous paints brightness of the main factors. Luminous paints were prepared with rare earth aluminate long afterglow luminescent powder, first is luminous powder surface modification, then investigate the influence of light emitting powder content, calcium carbonate, titanium dioxide, nano alumina and other fillers on the luminescent properties of the paints. It was concluded that the water resistance of the luminescent powder is better and the brightness can be improved after the modification of anhydrous alcohol. The addition of nano-alumina can improve the brightness of the system, and can effectively enhance the hardness of the paints. In the paints, the two kinds of components of carbonate and titanium dioxide have little effect on the luminescent brightness of the painting.

Targeted modulation of reactive oxygen species in the vascular endothelium

OpenAIRE

Shuvaev, Vladimir V.; Muzykantov, Vladimir R.

2011-01-01

Endothelial cells lining vascular luminal surface represent an important site of signaling and injurious effects of reactive oxygen species (ROS) produced by other cells and endothelium itself in ischemia, inflammation and other pathological conditions. Targeted delivery of ROS modulating enzymes conjugated with antibodies to endothelial surface molecules (vascular immunotargeting) provides site-specific interventions in the endothelial ROS, unattainable by other formulations including PEG-mo...

Nonlinear mapping of the luminance in dual-layer high dynamic range displays

Science.gov (United States)

Guarnieri, Gabriele; Ramponi, Giovanni; Bonfiglio, Silvio; Albani, Luigi

2009-02-01

It has long been known that the human visual system (HVS) has a nonlinear response to luminance. This nonlinearity can be quantified using the concept of just noticeable difference (JND), which represents the minimum amplitude of a specified test pattern an average observer can discern from a uniform background. The JND depends on the background luminance following a threshold versus intensity (TVI) function. It is possible to define a curve which maps physical luminances into a perceptually linearized domain. This mapping can be used to optimize a digital encoding, by minimizing the visibility of quantization noise. It is also commonly used in medical applications to display images adapting to the characteristics of the display device. High dynamic range (HDR) displays, which are beginning to appear on the market, can display luminance levels outside the range in which most standard mapping curves are defined. In particular, dual-layer LCD displays are able to extend the gamut of luminance offered by conventional liquid crystals towards the black region; in such areas suitable and HVS-compliant luminance transformations need to be determined. In this paper we propose a method, which is primarily targeted to the extension of the DICOM curve used in medical imaging, but also has a more general application. The method can be modified in order to compensate for the ambient light, which can be significantly greater than the black level of an HDR display and consequently reduce the visibility of the details in dark areas.

Podoplanin regulates mammary stem cell function and tumorigenesis by potentiating Wnt/β-catenin signaling.

Science.gov (United States)

Bresson, Laura; Faraldo, Marisa M; Di-Cicco, Amandine; Quintanilla, Miguel; Glukhova, Marina A; Deugnier, Marie-Ange

2018-02-21

Stem cells (SCs) drive mammary development, giving rise postnatally to an epithelial bilayer composed of luminal and basal myoepithelial cells. Dysregulation of SCs is thought to be at the origin of certain breast cancers; however, the molecular identity of SCs and the factors regulating their function remain poorly defined. We identified the transmembrane protein podoplanin (Pdpn) as a specific marker of the basal compartment, including multipotent SCs, and found Pdpn localized at the basal-luminal interface. Embryonic deletion of Pdpn targeted to basal cells diminished basal and luminal SC activity and affected the expression of several Wnt/β-catenin signaling components in basal cells. Moreover, Pdpn loss attenuated mammary tumor formation in a mouse model of β-catenin-induced breast cancer, limiting tumor-initiating cell expansion and promoting molecular features associated with mesenchymal-to-epithelial cell transition. In line with the loss-of-function data, we demonstrated that mechanistically Pdpn enhances Wnt/β-catenin signaling in mammary basal cells. Overall, this study uncovers a role for Pdpn in mammary SC function and, importantly, identifies Pdpn as a new regulator of Wnt/β-catenin signaling, a key pathway in mammary development and tumorigenesis. © 2018. Published by The Company of Biologists Ltd.

TriPer, an optical probe tuned to the endoplasmic reticulum tracks changes in luminal H2O2.

Science.gov (United States)

Melo, Eduardo Pinho; Lopes, Carlos; Gollwitzer, Peter; Lortz, Stephan; Lenzen, Sigurd; Mehmeti, Ilir; Kaminski, Clemens F; Ron, David; Avezov, Edward

2017-03-27

The fate of hydrogen peroxide (H 2 O 2 ) in the endoplasmic reticulum (ER) has been inferred indirectly from the activity of ER-localized thiol oxidases and peroxiredoxins, in vitro, and the consequences of their genetic manipulation, in vivo. Over the years hints have suggested that glutathione, puzzlingly abundant in the ER lumen, might have a role in reducing the heavy burden of H 2 O 2 produced by the luminal enzymatic machinery for disulfide bond formation. However, limitations in existing organelle-targeted H 2 O 2 probes have rendered them inert in the thiol-oxidizing ER, precluding experimental follow-up of glutathione's role in ER H 2 O 2 metabolism. Here we report on the development of TriPer, a vital optical probe sensitive to changes in the concentration of H 2 O 2 in the thiol-oxidizing environment of the ER. Consistent with the hypothesized contribution of oxidative protein folding to H 2 O 2 production, ER-localized TriPer detected an increase in the luminal H 2 O 2 signal upon induction of pro-insulin (a disulfide-bonded protein of pancreatic β-cells), which was attenuated by the ectopic expression of catalase in the ER lumen. Interfering with glutathione production in the cytosol by buthionine sulfoximine (BSO) or enhancing its localized destruction by expression of the glutathione-degrading enzyme ChaC1 in the lumen of the ER further enhanced the luminal H 2 O 2 signal and eroded β-cell viability. A tri-cysteine system with a single peroxidatic thiol enables H 2 O 2 detection in oxidizing milieux such as that of the ER. Tracking ER H 2 O 2 in live pancreatic β-cells points to a role for glutathione in H 2 O 2 turnover.

A generalizable platform for interrogating target- and signal-specific consequences of electrophilic modifications in redox-dependent cell signaling.

Science.gov (United States)

Lin, Hong-Yu; Haegele, Joseph A; Disare, Michael T; Lin, Qishan; Aye, Yimon

2015-05-20

Despite the known propensity of small-molecule electrophiles to react with numerous cysteine-active proteins, biological actions of individual signal inducers have emerged to be chemotype-specific. To pinpoint and quantify the impacts of modifying one target out of the whole proteome, we develop a target-protein-personalized "electrophile toolbox" with which specific intracellular targets can be selectively modified at a precise time by specific reactive signals. This general methodology, T-REX (targetable reactive electrophiles and oxidants), is established by (1) constructing a platform that can deliver a range of electronic and sterically different bioactive lipid-derived signaling electrophiles to specific proteins in cells; (2) probing the kinetics of targeted delivery concept, which revealed that targeting efficiency in cells is largely driven by initial on-rate of alkylation; and (3) evaluating the consequences of protein-target- and small-molecule-signal-specific modifications on the strength of downstream signaling. These data show that T-REX allows quantitative interrogations into the extent to which the Nrf2 transcription factor-dependent antioxidant response element (ARE) signaling is activated by selective electrophilic modifications on Keap1 protein, one of several redox-sensitive regulators of the Nrf2-ARE axis. The results document Keap1 as a promiscuous electrophile-responsive sensor able to respond with similar efficiencies to discrete electrophilic signals, promoting comparable strength of Nrf2-ARE induction. T-REX is also able to elicit cell activation in cases in which whole-cell electrophile flooding fails to stimulate ARE induction prior to causing cytotoxicity. The platform presents a previously unavailable opportunity to elucidate the functional consequences of small-molecule-signal- and protein-target-specific electrophilic modifications in an otherwise unaffected cellular background.

An analytical model for backscattered luminance in fog: comparisons with Monte Carlo computations and experimental results

International Nuclear Information System (INIS)

Taillade, Frédéric; Dumont, Eric; Belin, Etienne

2008-01-01

We propose an analytical model for backscattered luminance in fog and derive an expression for the visibility signal-to-noise ratio as a function of meteorological visibility distance. The model uses single scattering processes. It is based on the Mie theory and the geometry of the optical device (emitter and receiver). In particular, we present an overlap function and take the phase function of fog into account. The results of the backscattered luminance obtained with our analytical model are compared to simulations made using the Monte Carlo method based on multiple scattering processes. An excellent agreement is found in that the discrepancy between the results is smaller than the Monte Carlo standard uncertainties. If we take no account of the geometry of the optical device, the results of the model-estimated backscattered luminance differ from the simulations by a factor 20. We also conclude that the signal-to-noise ratio computed with the Monte Carlo method and our analytical model is in good agreement with experimental results since the mean difference between the calculations and experimental measurements is smaller than the experimental uncertainty

Luminal nucleotides are tonic inhibitors of renal tubular transport

DEFF Research Database (Denmark)

Leipziger, Jens Georg

2011-01-01

PURPOSE OF REVIEW: Extracellular ATP is an essential local signaling molecule in all organ systems. In the kidney, purinergic signaling is involved in an array of functions and this review highlights those of relevance for renal tubular transport. RECENT FINDINGS: Purinergic receptors are express...... discovered as an important signaling compartment in which local purinergic signaling determines an inhibitory tone for renal tubular transport. Blocking components of this system leads to tubular hyper-absorption, volume retention and elevated blood pressure.......PURPOSE OF REVIEW: Extracellular ATP is an essential local signaling molecule in all organ systems. In the kidney, purinergic signaling is involved in an array of functions and this review highlights those of relevance for renal tubular transport. RECENT FINDINGS: Purinergic receptors are expressed...... in all renal tubular segments and their stimulation generally leads to transport inhibition. Recent evidence has identified the tubular lumen as a restricted space for purinergic signaling. The concentrations of ATP in the luminal fluids are sufficiently high to inflict a tonic inhibition of renal...

Targeting Apoptosis Signaling in Pancreatic Cancer

International Nuclear Information System (INIS)

Fulda, Simone

2011-01-01

The ability to escape apoptosis or programmed cell death is a hallmark of human cancers, for example pancreatic cancer. This can promote tumorigenesis, since too little cell death by apoptosis disturbs tissue homeostasis. Additionally, defective apoptosis signaling is the underlying cause of failure to respond to current treatment approaches, since therapy-mediated antitumor activity requires the intactness of apoptosis signaling pathways in cancer cells. Thus, the elucidation of defects in the regulation of apoptosis in pancreatic carcinoma can result in the identification of novel targets for therapeutic interference and for exploitation for cancer drug discovery

Targeting Apoptosis Signaling in Pancreatic Cancer

Energy Technology Data Exchange (ETDEWEB)

Fulda, Simone [Institute for Experimental Cancer Research in Pediatrics, Goethe-University Frankfurt, Komturstr. 3a, 60528 Frankfurt (Germany)

2011-01-11

The ability to escape apoptosis or programmed cell death is a hallmark of human cancers, for example pancreatic cancer. This can promote tumorigenesis, since too little cell death by apoptosis disturbs tissue homeostasis. Additionally, defective apoptosis signaling is the underlying cause of failure to respond to current treatment approaches, since therapy-mediated antitumor activity requires the intactness of apoptosis signaling pathways in cancer cells. Thus, the elucidation of defects in the regulation of apoptosis in pancreatic carcinoma can result in the identification of novel targets for therapeutic interference and for exploitation for cancer drug discovery.

Effects of absolute luminance and luminance contrast on visual search in low mesopic environments.

Science.gov (United States)

Hunter, Mathew; Godde, Ben; Olk, Bettina

2018-03-26

Diverse adaptive visual processing mechanisms allow us to complete visual search tasks in a wide visual photopic range (>0.6 cd/m 2 ). Whether search strategies or mechanisms known from this range extend below, in the mesopic and scotopic luminance spectra (search in more complex-feature and conjunction-search paradigms. The results verify the previously reported deficiency windows defined by an interaction of base luminance and luminance contrast for more complex visual-search tasks. Based on significant regression analyses, a more precise definition of the magnitude of contribution of different contrast parameters. Characterized feature search patterns had approximately a 2.5:1 ratio of contribution from the Michelson contrast property relative to Weber contrast, whereas the ratio was approximately 1:1 in a serial-search condition. The results implicate near-complete magnocellular isolation in a visual-search paradigm that has yet to be demonstrated. Our analyses provide a new method of characterizing visual search and the first insight in its underlying mechanisms in luminance environments in the low mesopic and scotopic spectra.

The effects of luminance contrast, colour combinations, font, and search time on brand icon legibility.

Science.gov (United States)

Ko, Ya-Hsien

2017-11-01

This study explored and identified the effects of luminance contrast, colour combinations, font, and search time on brand icon legibility. A total of 108 participants took part in the experiment. As designed, legibility was measured as a function of the following independent variables: four levels of luminance contrast, sixteen target/background colour combinations, two fonts, and three search times. The results showed that a luminance contrast of 18:1 provided readers with the best legibility. Yellow on black, yellow on blue, and white on blue were the three most legible colour combinations. One of this study's unique findings was that colour combinations may play an even more important role than luminance contrast in the overall legibility of brand icon design. The 12-s search time corresponded with the highest legibility. Arial font was more legible than Times New Roman. These results provide some guidance for brand icon and product advertisement design. Copyright © 2017 Elsevier Ltd. All rights reserved.

Daylight calculations using constant luminance curves

Energy Technology Data Exchange (ETDEWEB)

Betman, E. [CRICYT, Mendoza (Argentina). Laboratorio de Ambiente Humano y Vivienda

2005-02-01

This paper presents a simple method to manually estimate daylight availability and to make daylight calculations using constant luminance curves calculated with local illuminance and irradiance data and the all-weather model for sky luminance distribution developed in the Atmospheric Science Research Center of the University of New York (ARSC) by Richard Perez et al. Work with constant luminance curves has the advantage that daylight calculations include the problem's directionality and preserve the information of the luminous climate of the place. This permits accurate knowledge of the resource and a strong basis to establish conclusions concerning topics related to the energy efficiency and comfort in buildings. The characteristics of the proposed method are compared with the method that uses the daylight factor. (author)

EVOLUTION OF THE MOST LUMINOUS DUSTY GALAXIES

International Nuclear Information System (INIS)

Weedman, Daniel W.; Houck, James R.

2009-01-01

A summary of mid-infrared continuum luminosities arising from dust is given for very luminous galaxies, L IR > 10 12 L sun , with 0.005 0.7 in the 9.7 μm silicate absorption feature (i.e., half of the continuum is absorbed) and having equivalent width of the 6.2 μm polycyclic aromatic hydrocarbon feature ν (8 μm) for the most luminous obscured AGNs is found to scale as (1+z) 2.6 to z = 2.8. For unobscured AGNs, the scaling with redshift is similar, but luminosities νL ν (8 μm) are approximately three times greater for the most luminous sources. Using both obscured and unobscured AGNs having total infrared fluxes from the Infrared Astronomical Satellite, empirical relations are found between νL ν (8 μm) and L IR . Combining these relations with the redshift scaling of luminosity, we conclude that the total infrared luminosities for the most luminous obscured AGNs, L IR (AGN obscured ) in L sun , scale as log L IR (AGN obscured ) = 12.3 ± 0.25 + 2.6(±0.3)log(1+z), and for the most luminous unobscured AGNs, scale as log L IR (AGN1) = 12.6(±0.15) + 2.6(±0.3)log(1+z). We previously determined that the most luminous starbursts scale as log L IR (SB) = 11.8 ± 0.3 + 2.5(±0.3)log(1+z), indicating that the most luminous AGNs are about 10 times more luminous than the most luminous starbursts. Results are consistent with obscured and unobscured AGNs having the same total luminosities with differences arising only from orientation, such that the obscured AGNs are observed through very dusty clouds which extinct about 50% of the intrinsic luminosity at 8 μm. Extrapolations of observable f ν (24 μm) to z = 6 are made using evolution results for these luminous sources. Both obscured and unobscured AGNs should be detected to z ∼ 6 by Spitzer surveys with f ν (24 μm) > 0.3 mJy, even without luminosity evolution for z > 2.5. By contrast, the most luminous starbursts cannot be detected for z > 3, even if luminosity evolution continues beyond z = 2.5.

Optimal combination of illusory and luminance-defined 3-D surfaces: A role for ambiguity.

Science.gov (United States)

Hartle, Brittney; Wilcox, Laurie M; Murray, Richard F

2018-04-01

The shape of the illusory surface in stereoscopic Kanizsa figures is determined by the interpolation of depth from the luminance edges of adjacent inducing elements. Despite ambiguity in the position of illusory boundaries, observers reliably perceive a coherent three-dimensional (3-D) surface. However, this ambiguity may contribute additional uncertainty to the depth percept beyond what is expected from measurement noise alone. We evaluated the intrinsic ambiguity of illusory boundaries by using a cue-combination paradigm to measure the reliability of depth percepts elicited by stereoscopic illusory surfaces. We assessed the accuracy and precision of depth percepts using 3-D Kanizsa figures relative to luminance-defined surfaces. The location of the surface peak was defined by illusory boundaries, luminance-defined edges, or both. Accuracy and precision were assessed using a depth-discrimination paradigm. A maximum likelihood linear cue combination model was used to evaluate the relative contribution of illusory and luminance-defined signals to the perceived depth of the combined surface. Our analysis showed that the standard deviation of depth estimates was consistent with an optimal cue combination model, but the points of subjective equality indicated that observers consistently underweighted the contribution of illusory boundaries. This systematic underweighting may reflect a combination rule that attributes additional intrinsic ambiguity to the location of the illusory boundary. Although previous studies show that illusory and luminance-defined contours share many perceptual similarities, our model suggests that ambiguity plays a larger role in the perceptual representation of illusory contours than of luminance-defined contours.

Dynamic encoding of natural luminance sequences by LGN bursts.

Directory of Open Access Journals (Sweden)

Nicholas A Lesica

2006-07-01

Full Text Available In the lateral geniculate nucleus (LGN of the thalamus, visual stimulation produces two distinct types of responses known as tonic and burst. Due to the dynamics of the T-type Ca(2+ channels involved in burst generation, the type of response evoked by a particular stimulus depends on the resting membrane potential, which is controlled by a network of modulatory connections from other brain areas. In this study, we use simulated responses to natural scene movies to describe how modulatory and stimulus-driven changes in LGN membrane potential interact to determine the luminance sequences that trigger burst responses. We find that at low resting potentials, when the T channels are de-inactivated and bursts are relatively frequent, an excitatory stimulus transient alone is sufficient to evoke a burst. However, to evoke a burst at high resting potentials, when the T channels are inactivated and bursts are relatively rare, prolonged inhibitory stimulation followed by an excitatory transient is required. We also observe evidence of these effects in vivo, where analysis of experimental recordings demonstrates that the luminance sequences that trigger bursts can vary dramatically with the overall burst percentage of the response. To characterize the functional consequences of the effects of resting potential on burst generation, we simulate LGN responses to different luminance sequences at a range of resting potentials with and without a mechanism for generating bursts. Using analysis based on signal detection theory, we show that bursts enhance detection of specific luminance sequences, ranging from the onset of excitatory sequences at low resting potentials to the offset of inhibitory sequences at high resting potentials. These results suggest a dynamic role for burst responses during visual processing that may change according to behavioral state.

Survival signalling and apoptosis resistance in glioblastomas: opportunities for targeted therapeutics

Directory of Open Access Journals (Sweden)

Krakstad Camilla

2010-06-01

Full Text Available Abstract Glioblastoma multiforme (GBM is the most common primary brain tumour in adults and one of the most aggressive cancers in man. Despite technological advances in surgical management, combined regimens of radiotherapy with new generation chemotherapy, the median survival for these patients is 14.6 months. This is largely due to a highly deregulated tumour genome with opportunistic deletion of tumour suppressor genes, amplification and/or mutational hyper-activation of receptor tyrosine kinase receptors. The net result of these genetic changes is augmented survival pathways and systematic defects in the apoptosis signalling machinery. The only randomised, controlled phase II trial conducted targeting the epidermal growth factor receptor (EGFR signalling with the small molecule inhibitor, erlotinib, has showed no therapeutic benefit. Survival signalling and apoptosis resistance in GBMs can be viewed as two sides of the same coin. Targeting increased survival is unlikely to be efficacious without at the same time targeting apoptosis resistance. We have critically reviewed the literature regarding survival and apoptosis signalling in GBM, and highlighted experimental, preclinical and recent clinical trials attempting to target these pathways. Combined therapies simultaneously targeting apoptosis and survival signalling defects might shift the balance from tumour growth stasis to cytotoxic therapeutic responses that might be associated with greater therapeutic benefits.

A Practical Device for Measuring the Luminance Distribution

Directory of Open Access Journals (Sweden)

Thijs Kruisselbrink

2017-06-01

Full Text Available Various applications in building lighting such as automated daylight systems, dynamic lighting control systems, lighting simulations, and glare analyzes can be optimized using information on the actual luminance distributions of the surroundings. Currently, commercially available luminance distribution measurement devices are often not suitable for these kind of applications or simply too expensive for broad application. This paper describes the development of a practical and autonomous luminance distribution measurement device based on a credit card-sized single-board computer and a camera system. The luminance distribution was determined by capturing High Dynamic Range images and translating the RGB information to the CIE XYZ color space. The High Dynamic Range technology was essential to accurately capture the data needed to calculate the luminance distribution because it allows to capture luminance ranges occurring in real scenarios. The measurement results were represented in accordance with established methods in the field of daylighting. Measurements showed that the accuracy of the luminance distribution measurement device ranged from 5% to 20% (worst case which was deemed acceptable for practical measurements and broad applications in the building realm.

Targeted modulation of reactive oxygen species in the vascular endothelium.

Science.gov (United States)

Shuvaev, Vladimir V; Muzykantov, Vladimir R

2011-07-15

'Endothelial cells lining vascular luminal surface represent an important site of signaling and injurious effects of reactive oxygen species (ROS) produced by other cells and endothelium itself in ischemia, inflammation and other pathological conditions. Targeted delivery of ROS modulating enzymes conjugated with antibodies to endothelial surface molecules (vascular immunotargeting) provides site-specific interventions in the endothelial ROS, unattainable by other formulations including PEG-modified enzymes. Targeting of ROS generating enzymes (e.g., glucose oxidase) provides ROS- and site-specific models of endothelial oxidative stress, whereas targeting of antioxidant enzymes SOD and catalase offers site-specific quenching of superoxide anion and H(2)O(2). These targeted antioxidant interventions help to clarify specific role of endothelial ROS in vascular and pulmonary pathologies and provide basis for design of targeted therapeutics for treatment of these pathologies. In particular, antibody/catalase conjugates alleviate acute lung ischemia/reperfusion injury, whereas antibody/SOD conjugates inhibit ROS-mediated vasoconstriction and inflammatory endothelial signaling. Encapsulation in protease-resistant, ROS-permeable carriers targeted to endothelium prolongs protective effects of antioxidant enzymes, further diversifying the means for targeted modulation of endothelial ROS. Copyright © 2011 Elsevier B.V. All rights reserved.

Conjunctions of colour, luminance and orientation: the role of colour and luminance contrast on saliency and proximity grouping in texture segregation.

Science.gov (United States)

Leonards, U; Singer, W

2000-01-01

To examine whether perceptual grouping on the basis of orientation can be performed simultaneously with or only subsequently to grouping according to colour or luminance, we tested whether subjects are able to segregate arrays of texture elements that differ from surrounding elements by conjunctions of either (i) colour and orientation, or (ii) luminance contrast and orientation, or (iii) luminance contrast polarity and orientation. Subjects were able to use conjunctions between luminance and orientation for segregation but not conjunctions between colour or contrast polarity and orientation. Our results suggest that (i) in agreement with earlier findings, there seem to exist no specific conjunction detectors for colour and orientation or contrast polarity and orientation, and (ii) when orientation defined textures are to be distinguished by virtue of differences in luminance, colour, or contrast polarity, luminance provides a much stronger cue than colour or contrast polarity for saliency-based orientation grouping.

A single peroxisomal targeting signal mediates matrix protein import in diatoms.

Directory of Open Access Journals (Sweden)

Nicola H Gonzalez

Full Text Available Peroxisomes are single membrane bound compartments. They are thought to be present in almost all eukaryotic cells, although the bulk of our knowledge about peroxisomes has been generated from only a handful of model organisms. Peroxisomal matrix proteins are synthesized cytosolically and posttranslationally imported into the peroxisomal matrix. The import is generally thought to be mediated by two different targeting signals. These are respectively recognized by the two import receptor proteins Pex5 and Pex7, which facilitate transport across the peroxisomal membrane. Here, we show the first in vivo localization studies of peroxisomes in a representative organism of the ecologically relevant group of diatoms using fluorescence and transmission electron microscopy. By expression of various homologous and heterologous fusion proteins we demonstrate that targeting of Phaeodactylum tricornutum peroxisomal matrix proteins is mediated only by PTS1 targeting signals, also for proteins that are in other systems imported via a PTS2 mode of action. Additional in silico analyses suggest this surprising finding may also apply to further diatoms. Our data suggest that loss of the PTS2 peroxisomal import signal is not reserved to Caenorhabditis elegans as a single exception, but has also occurred in evolutionary divergent organisms. Obviously, targeting switching from PTS2 to PTS1 across different major eukaryotic groups might have occurred for different reasons. Thus, our findings question the widespread assumption that import of peroxisomal matrix proteins is generally mediated by two different targeting signals. Our results implicate that there apparently must have been an event causing the loss of one targeting signal even in the group of diatoms. Different possibilities are discussed that indicate multiple reasons for the detected targeting switching from PTS2 to PTS1.

Chromatic blur perception in the presence of luminance contrast.

Science.gov (United States)

Jennings, Ben J; Kingdom, Frederick A A

2017-06-01

Hel-Or showed that blurring the chromatic but not the luminance layer of an image of a natural scene failed to elicit any impression of blur. Subsequent studies have suggested that this effect is due either to chromatic blur being masked by spatially contiguous luminance edges in the scene (Journal of Vision 13 (2013) 14), or to a relatively compressed transducer function for chromatic blur (Journal of Vision 15 (2015) 6). To test between the two explanations we conducted experiments using as stimuli both images of natural scenes as well as simple edges. First, we found that in color-and-luminance images of natural scenes more chromatic blur was needed to perceptually match a given level of blur in an isoluminant, i.e. colour-only scene. However, when the luminance layer in the scene was rotated relative to the chromatic layer, thus removing the colour-luminance edge correlations, the matched blur levels were near equal. Both results are consistent with Sharman et al.'s explanation. Second, when observers matched the blurs of luminance-only with isoluminant scenes, the matched blurs were equal, against Kingdom et al.'s prediction. Third, we measured the perceived blur in a square-wave as a function of (i) contrast (ii) number of luminance edges and (iii) the relative spatial phase between the colour and luminance edges. We found that the perceived chromatic blur was dependent on both relative phase and the number of luminance edges, or dependent on the luminance contrast if only a single edge is present. We conclude that this Hel-Or effect is largely due to masking of chromatic blur by spatially contiguous luminance edges. Copyright © 2017 Elsevier Ltd. All rights reserved.

Luminance noise as a novel approach for measuring contrast sensitivity within the magnocellular and parvocellular pathways.

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Hall, Cierra M; McAnany, J Jason

2017-07-01

This study evaluated the extent to which different types of luminance noise can be used to target selectively the inferred magnocellular (MC) and parvocellular (PC) visual pathways. Letter contrast sensitivity (CS) was measured for three visually normal subjects for letters of different size (0.8°-5.3°) under established paradigms intended to target the MC pathway (steady-pedestal paradigm) and PC pathway (pulsed-pedestal paradigm). Results obtained under these paradigms were compared to those obtained in asynchronous static noise (a field of unchanging luminance noise) and asynchronous dynamic noise (a field of randomly changing luminance noise). CS was measured for letters that were high- and low-pass filtered using a range of filter cutoffs to quantify the object frequency information (cycles per letter) mediating letter identification, which was used as an index of the pathway mediating CS. A follow-up experiment was performed to determine the range of letter duration over which MC and PC pathway CS can be targeted. Analysis of variance indicated that the object frequencies measured under the static noise and steady-pedestal paradigms did not differ significantly (p ≥ 0.065), but differed considerably from those measured under the dynamic noise (both p noise, and in dynamic noise. These data suggest that the spatiotemporal characteristics of noise can be manipulated to target the inferred MC (static noise) and PC (dynamic noise) pathways. The results also suggest that CS within these pathways can be measured at long stimulus durations, which has potential importance in the design of future clinical CS tests.

MPD model for radar echo signal of hypersonic targets

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Xu Xuefei

2014-08-01

Full Text Available The stop-and-go (SAG model is typically used for echo signal received by the radar using linear frequency modulation pulse compression. In this study, the authors demonstrate that this model is not applicable to hypersonic targets. Instead of SAG model, they present a more realistic echo signal model (moving-in-pulse duration (MPD for hypersonic targets. Following that, they evaluate the performances of pulse compression under the SAG and MPD models by theoretical analysis and simulations. They found that the pulse compression gain has an increase of 3 dB by using the MPD model compared with the SAG model in typical cases.

Robust brightness enhancement across a luminance range of the glare illusion.

Science.gov (United States)

Tamura, Hideki; Nakauchi, Shigeki; Koida, Kowa

2016-01-01

The glare illusion refers to brightness enhancement and the perception of a self-luminous appearance that occurs when a central region is surrounded by a luminance gradient. The center region appears to be a light source, with its light dispersing into the surrounding region. If the luminous edge is critical for generating the illusion, modulating the perceived luminance of the image, and switching its appearance from luminous to nonluminous, would have a strong impact on lightness and brightness estimation. Here, we quantified the illusion in two ways, by assessing brightness enhancement and examining whether the center region appeared luminous. Thus, we could determine whether the two effects occurred jointly or independently. We examined a wide luminance range of center regions, from 0 to 200% relative to background. Brightness enhancement in the illusion was observed for a wide range of luminances (20% to 200% relative to background), while a luminous-white appearance was observed when the center region luminance was 145% of the background. These results exclude the possibility that brightness enhancement occurs because the stimuli appear self-luminous. We suggest that restoring the original image intensity precedes the perceptual process of lightness estimation.

TPC2 is a novel NAADP-sensitive Ca2+ release channel, operating as a dual sensor of luminal pH and Ca2+.

Science.gov (United States)

Pitt, Samantha J; Funnell, Tim M; Sitsapesan, Mano; Venturi, Elisa; Rietdorf, Katja; Ruas, Margarida; Ganesan, A; Gosain, Rajendra; Churchill, Grant C; Zhu, Michael X; Parrington, John; Galione, Antony; Sitsapesan, Rebecca

2010-11-05

Nicotinic acid adenine dinucleotide phosphate (NAADP) is a molecule capable of initiating the release of intracellular Ca(2+) required for many essential cellular processes. Recent evidence links two-pore channels (TPCs) with NAADP-induced release of Ca(2+) from lysosome-like acidic organelles; however, there has been no direct demonstration that TPCs can act as NAADP-sensitive Ca(2+) release channels. Controversial evidence also proposes ryanodine receptors as the primary target of NAADP. We show that TPC2, the major lysosomal targeted isoform, is a cation channel with selectivity for Ca(2+) that will enable it to act as a Ca(2+) release channel in the cellular environment. NAADP opens TPC2 channels in a concentration-dependent manner, binding to high affinity activation and low affinity inhibition sites. At the core of this process is the luminal environment of the channel. The sensitivity of TPC2 to NAADP is steeply dependent on the luminal [Ca(2+)] allowing extremely low levels of NAADP to open the channel. In parallel, luminal pH controls NAADP affinity for TPC2 by switching from reversible activation of TPC2 at low pH to irreversible activation at neutral pH. Further evidence earmarking TPCs as the likely pathway for NAADP-induced intracellular Ca(2+) release is obtained from the use of Ned-19, the selective blocker of cellular NAADP-induced Ca(2+) release. Ned-19 antagonizes NAADP-activation of TPC2 in a non-competitive manner at 1 μM but potentiates NAADP activation at nanomolar concentrations. This single-channel study provides a long awaited molecular basis for the peculiar mechanistic features of NAADP signaling and a framework for understanding how NAADP can mediate key physiological events.

Signal Detection, Target Tracking and Differential Geometry Applications to Statistical Inference

National Research Council Canada - National Science Library

Rao, C

1997-01-01

Signal detection and target tracking. A novel method known as polynomial rooting approach is proposed to obtain estimates of frequencies, amplitudes and noise variance of two-dimensional exponential signals...

Night sky luminance under clear sky conditions: Theory vs. experiment

International Nuclear Information System (INIS)

Kocifaj, Miroslav

2014-01-01

Sky glow is caused by both natural phenomena and factors of anthropogenic origin, and of the latter ground-based light sources are the most important contributors for they emit the spatially linked spectral radiant intensity distribution of artificial light sources, which are further modulated by local atmospheric optics and perceived as the diffuse light of a night sky. In other words, sky glow is closely related to a city's shape and pattern of luminaire distribution, in practical effect an almost arbitrary deployment of random orientation of heterogeneous electrical light sources. Thus the luminance gradation function measured in a suburban zone or near the edges of a city is linked to the City Pattern or vice versa. It is shown that clear sky luminance/radiance data recorded in an urban area can be used to retrieve the bulk luminous/radiant intensity distribution if some a-priori information on atmospheric aerosols is available. For instance, the single scattering albedo of aerosol particles is required under low turbidity conditions, as demonstrated on a targeted experiment in the city of Frýdek-Mistek. One of the main advantages of the retrieval method presented in this paper is that the single scattering approximation is satisfactorily accurate in characterizing the light field near the ground because the dominant contribution to the sky glow has originated from beams propagated along short optical paths. - Highlights: • Urban sky glow is interpreted in terms of city emission function. • Luminance function in a suburban zone is linked to the City Pattern. • Single scattering approximation is applicable in modeling urban sky glow. • Information on aerosols represents valuable inputs to the retrieval procedure. • Sky glow patterns vary with light source distribution and spectral emission

Identification of Different Classes of Luminal Progenitor Cells within Prostate Tumors

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Supreet Agarwal

2015-12-01

Full Text Available Primary prostate cancer almost always has a luminal phenotype. However, little is known about the stem/progenitor properties of transformed cells within tumors. Using the aggressive Pten/Tp53-null mouse model of prostate cancer, we show that two classes of luminal progenitors exist within a tumor. Not only did tumors contain previously described multipotent progenitors, but also a major population of committed luminal progenitors. Luminal cells, sorted directly from tumors or grown as organoids, initiated tumors of adenocarcinoma or multilineage histological phenotypes, which is consistent with luminal and multipotent differentiation potentials, respectively. Moreover, using organoids we show that the ability of luminal-committed progenitors to self-renew is a tumor-specific property, absent in benign luminal cells. Finally, a significant fraction of luminal progenitors survived in vivo castration. In all, these data reveal two luminal tumor populations with different stem/progenitor cell capacities, providing insight into prostate cancer cells that initiate tumors and can influence treatment response.

Identification of New Epididymal Luminal Fluid Proteins Involved in Sperm Maturation in Infertile Rats Treated by Dutasteride Using iTRAQ

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Shu-Wu Xie

2016-05-01

Full Text Available Background: Spermatozoa become mature and acquire fertilizing capacity during their passage through the epididymal lumen. In this study, we identified new epididymal luminal fluid proteins involved in sperm maturation in infertile rats by dutasteride, a dual 5α-reductase inhibitor, in order to provide potential epididymal targets for new contraceptives and infertility treatment. Methods: Male rats were treated with dutasteride for 28 consecutive days. We observed the protein expression profiles in the epididymal luminal fluids in infertile and normal rats using isobaric tags for relative and absolute quantitation (iTRAQ technique. The confidence of proteome data was validated by enzyme-linked immunosorbent assays. Results: 1045 proteins were tested, and 23 of them presented different expression profiling in the infertile and normal rats. The seven proteins were down-regulated, and 16 proteins were up-regulated. Among the seven proteins which were significantly down-regulated by dutasteride in the epididymal luminal fluids, there were three β-defensins (Defb2, Defb18 and Defb39, which maybe the key proteins involved in epididymal sperm maturation and male fertility. Conclusions: We report for the first time that dutasteride influences the protein expression profiling in the epididymal luminal fluids of rats, and this result provides some new epididymal targets for male contraception and infertility therapy.

Visual Perceptual Echo Reflects Learning of Regularities in Rapid Luminance Sequences.

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Chang, Acer Y-C; Schwartzman, David J; VanRullen, Rufin; Kanai, Ryota; Seth, Anil K

2017-08-30

A novel neural signature of active visual processing has recently been described in the form of the "perceptual echo", in which the cross-correlation between a sequence of randomly fluctuating luminance values and occipital electrophysiological signals exhibits a long-lasting periodic (∼100 ms cycle) reverberation of the input stimulus (VanRullen and Macdonald, 2012). As yet, however, the mechanisms underlying the perceptual echo and its function remain unknown. Reasoning that natural visual signals often contain temporally predictable, though nonperiodic features, we hypothesized that the perceptual echo may reflect a periodic process associated with regularity learning. To test this hypothesis, we presented subjects with successive repetitions of a rapid nonperiodic luminance sequence, and examined the effects on the perceptual echo, finding that echo amplitude linearly increased with the number of presentations of a given luminance sequence. These data suggest that the perceptual echo reflects a neural signature of regularity learning.Furthermore, when a set of repeated sequences was followed by a sequence with inverted luminance polarities, the echo amplitude decreased to the same level evoked by a novel stimulus sequence. Crucially, when the original stimulus sequence was re-presented, the echo amplitude returned to a level consistent with the number of presentations of this sequence, indicating that the visual system retained sequence-specific information, for many seconds, even in the presence of intervening visual input. Altogether, our results reveal a previously undiscovered regularity learning mechanism within the human visual system, reflected by the perceptual echo. SIGNIFICANCE STATEMENT How the brain encodes and learns fast-changing but nonperiodic visual input remains unknown, even though such visual input characterizes natural scenes. We investigated whether the phenomenon of "perceptual echo" might index such learning. The perceptual echo is a

Visual sensitivity for luminance and chromatic stimuli during the execution of smooth pursuit and saccadic eye movements.

Science.gov (United States)

Braun, Doris I; Schütz, Alexander C; Gegenfurtner, Karl R

2017-07-01

Visual sensitivity is dynamically modulated by eye movements. During saccadic eye movements, sensitivity is reduced selectively for low-spatial frequency luminance stimuli and largely unaffected for high-spatial frequency luminance and chromatic stimuli (Nature 371 (1994), 511-513). During smooth pursuit eye movements, sensitivity for low-spatial frequency luminance stimuli is moderately reduced while sensitivity for chromatic and high-spatial frequency luminance stimuli is even increased (Nature Neuroscience, 11 (2008), 1211-1216). Since these effects are at least partly of different polarity, we investigated the combined effects of saccades and smooth pursuit on visual sensitivity. For the time course of chromatic sensitivity, we found that detection rates increased slightly around pursuit onset. During saccades to static and moving targets, detection rates dropped briefly before the saccade and reached a minimum at saccade onset. This reduction of chromatic sensitivity was present whenever a saccade was executed and it was not modified by subsequent pursuit. We also measured contrast sensitivity for flashed high- and low-spatial frequency luminance and chromatic stimuli during saccades and pursuit. During saccades, the reduction of contrast sensitivity was strongest for low-spatial frequency luminance stimuli (about 90%). However, a significant reduction was also present for chromatic stimuli (about 58%). Chromatic sensitivity was increased during smooth pursuit (about 12%). These results suggest that the modulation of visual sensitivity during saccades and smooth pursuit is more complex than previously assumed. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Weak Lensing Masses of Filaments between Luminous Red Galaxies

Science.gov (United States)

Epps, Seth D.; Hudson, Michael J.

2017-07-01

In the standard model of non-linear structure formation, a cosmic web of dark-matter-dominated filaments connects dark matter haloes. In this paper, we stack the weak lensing signal of an ensemble of filaments between groups and clusters of galaxies. Specifically, we detect the weak lensing signal, using CFHTLenS galaxy ellipticities, from stacked filaments between Sloan Digital Sky Survey (SDSS)-III/Baryon Oscillation Spectroscopic Survey luminous red galaxies (LRGs). As a control, we compare the physical LRG pairs with projected LRG pairs that are more widely separated in redshift space. We detect the excess filament mass density in the projected pairs at the 5σ level, finding a mass of (1.6 ± 0.3) × 1013 M⊙ for a stacked filament region 7.1 h-1 Mpc long and 2.5 h-1 Mpc wide. This filament signal is compared with a model based on the three-point galaxy-galaxy-convergence correlation function, as developed in Clampitt et al., yielding reasonable agreement.

Luminous bacteria cultured from fish guts in the Gulf of Oman.

Science.gov (United States)

Makemson, J C; Hermosa, G V

1999-01-01

The incidence of culturable luminous bacteria in Omani market fish guts was correlated to habitat type amongst 109 species of fish. Isolated representative luminous bacteria were compared to known species using the Biolog system (95 traits/isolate) and cluster analysis, which showed that the main taxa present in fish guts were clades related to Vibrio harveyi and Photobacterium species with sporadic incidence of P. phosphoreum. The luminous isolates from gut of the slip-mouth (barred pony fish), Leiognathus fasciatus, were mainly a type related to Photobacterium but phenotypically different from known species. These luminous gut bacteria were identical with the bacteria in the light organ, indicating that the light organ supplies a significant quantity of luminous bacteria to the gut. In many of the fish that lack light organs, luminous bacteria were also the dominant bacterial type in the gut, while in some others luminous bacteria were encountered sporadically and at low densities, reflecting the incidence of culturable luminous bacteria in seawater. Pelagic fish contained the highest incidence of culturable luminous bacteria and reef-associated fish the lowest. No correlation was found between the incidence of culturable luminous bacteria and the degree to which fish produce a melanin-covered gut. Copyright 1999 John Wiley & Sons, Ltd.

Id-1 is not expressed in the luminal epithelial cells of mammary glands

International Nuclear Information System (INIS)

Uehara, Norihisa; Chou, Yu-Chien; Galvez, Jose J; Candia, Paola de; Cardiff, Robert D; Benezra, Robert; Shyamala, Gopalan

2003-01-01

The family of inhibitor of differentiation/DNA binding (Id) proteins is known to regulate development in several tissues. One member of this gene family, Id-1, has been implicated in mammary development and carcinogenesis. Mammary glands contain various cell types, among which the luminal epithelial cells are primarily targeted for proliferation, differentiation and carcinogenesis. Therefore, to assess the precise significance of Id-1 in mammary biology and carcinogenesis, we examined its cellular localization in vivo using immunohistochemistry. Extracts of whole mammary glands from wild type and Id-1 null mutant mice, and tissue sections from paraffin-embedded mouse mammary glands from various developmental stages and normal human breast were subjected to immunoblot and immunohistochemical analyses, respectively. In both these procedures, an anti-Id-1 rabbit polyclonal antibody was used for detection of Id-1. In immunoblot analyses, using whole mammary gland extracts, Id-1 was detected. In immunohistochemical analyses, however, Id-1 was not detected in the luminal epithelial cells of mammary glands during any stage of development, but it was detected in vascular endothelial cells. Id-1 is not expressed in the luminal epithelial cells of mammary glands

Targeting Apoptosis Signaling Pathways for Anticancer Therapy

Energy Technology Data Exchange (ETDEWEB)

Fulda, Simone, E-mail: simone.fulda@kgu.de [Institute for Experimental Cancer Research in Pediatrics, Goethe-University, Frankfurt (Germany)

2011-08-29

Treatment approaches for cancer, for example chemotherapy, radiotherapy, or immunotherapy, primarily act by inducing cell death in cancer cells. Consequently, the inability to trigger cell death pathways or alternatively, evasion of cancer cells to the induction of cell death pathways can result in resistance of cancers to current treatment protocols. Therefore, in order to overcome treatment resistance a better understanding of the underlying mechanisms that regulate cell death and survival pathways in cancers and in response to cancer therapy is necessary to develop molecular-targeted therapies. This strategy should lead to more effective and individualized treatment strategies that selectively target deregulated signaling pathways in a tumor type- and patient-specific manner.

Targeting Apoptosis Signaling Pathways for Anticancer Therapy

International Nuclear Information System (INIS)

Fulda, Simone

2011-01-01

Treatment approaches for cancer, for example chemotherapy, radiotherapy, or immunotherapy, primarily act by inducing cell death in cancer cells. Consequently, the inability to trigger cell death pathways or alternatively, evasion of cancer cells to the induction of cell death pathways can result in resistance of cancers to current treatment protocols. Therefore, in order to overcome treatment resistance a better understanding of the underlying mechanisms that regulate cell death and survival pathways in cancers and in response to cancer therapy is necessary to develop molecular-targeted therapies. This strategy should lead to more effective and individualized treatment strategies that selectively target deregulated signaling pathways in a tumor type- and patient-specific manner.

Relationship between luminous fish and symbiosis. I. Comparative studies of lipopolysaccharides isolated from symbiotic luminous bacteria of the luminous marine fish, Physiculus japonicus.

Science.gov (United States)

Kuwae, T; Andoh, M; Fukasawa, S; Kurata, M

1983-01-01

In order to investigate the relationship between host and symbiosis in the luminous marine fish, Physiculus japonicus, the bacterial lipopolysaccharides (LPS) of symbiotic luminous bacteria were compared serologically and electrophoretically. Five symbiotic luminous bacteria (PJ strains) were separately isolated from five individuals of this fish species caught at three points, off the coasts of Chiba, Nakaminato, and Oharai. LPS preparations were made from these bacteria by Westphal's phenol-water method and highly purified by repeated ultracentrifugation. These LPSs contained little or no 2-keto-3-deoxyoctonate and had powerful mitogenic activity. In sodium dodecylsulfate polyacrylamide gel electrophoresis, these PJ-1 to -5 LPSs were separated by their electrophoretic patterns into three groups; the first group included PJ-1 and PJ-4, the second group PJ-2 and PJ-3, and the third group PJ-5 alone. The results agreed with those of the double immunodiffusion test; precipitin lines completely coalesced within each group but not with other groups. In immunoelectrophoresis, one precipitin line was observed between anti PJ-2 LPS serum and PJ-5 LPS but the electrophoretic mobility of PJ-5 LPS was clearly different from that of the PJ-2 LPS group. Furthermore, in a 50% inhibition test with PJ-2 LPS by the passive hemolysis system, the doses of PJ-2 LPS, PJ-3 LPS, and PJ-5 LPS required for 50% inhibition (ID50) in this system were 0.25, 0.25, and 21.6 micrograms/ml for each alkali-treated LPS, respectively, and the ID50's of both PJ-1 LPS and PJ-4 LPS were above 1,000 micrograms/ml. These results indicate that PJ-5 LPS has an antigenic determinant partially in common with LPS from the PJ-2 group but not with LPS from the PJ-1 group and that the symbiotic luminous bacterium PJ-5 is more closely related to the PJ-2 group than to the PJ-1 group. These results show that the species Physiculus japonicus is symbiotically associated with at least three immunologically different

Standard deviation of luminance distribution affects lightness and pupillary response.

Science.gov (United States)

Kanari, Kei; Kaneko, Hirohiko

2014-12-01

We examined whether the standard deviation (SD) of luminance distribution serves as information of illumination. We measured the lightness of a patch presented in the center of a scrambled-dot pattern while manipulating the SD of the luminance distribution. Results showed that lightness decreased as the SD of the surround stimulus increased. We also measured pupil diameter while viewing a similar stimulus. The pupil diameter decreased as the SD of luminance distribution of the stimuli increased. We confirmed that these results were not obtained because of the increase of the highest luminance in the stimulus. Furthermore, results of field measurements revealed a correlation between the SD of luminance distribution and illuminance in natural scenes. These results indicated that the visual system refers to the SD of the luminance distribution in the visual stimulus to estimate the scene illumination.

Target acquisition performance : Effects of target aspect angle, dynamic imaging and signal processing

NARCIS (Netherlands)

Beintema, J.A.; Bijl, P.; Hogervorst, M.A.; Dijk, J.

2008-01-01

In an extensive Target Acquisition (TA) performance study, we recorded static and dynamic imagery of a set of military and civilian two-handheld objects at a range of distances and aspect angles with an under-sampled uncooled thermal imager. Next, we applied signal processing techniques including

Therapeutic Targeting of the IL-6 Trans-Signaling/Mechanistic Target of Rapamycin Complex 1 Axis in Pulmonary Emphysema.

Science.gov (United States)

Ruwanpura, Saleela M; McLeod, Louise; Dousha, Lovisa F; Seow, Huei J; Alhayyani, Sultan; Tate, Michelle D; Deswaerte, Virginie; Brooks, Gavin D; Bozinovski, Steven; MacDonald, Martin; Garbers, Christoph; King, Paul T; Bardin, Philip G; Vlahos, Ross; Rose-John, Stefan; Anderson, Gary P; Jenkins, Brendan J

2016-12-15

The potent immunomodulatory cytokine IL-6 is consistently up-regulated in human lungs with emphysema and in mouse emphysema models; however, the mechanisms by which IL-6 promotes emphysema remain obscure. IL-6 signals using two distinct modes: classical signaling via its membrane-bound IL-6 receptor (IL-6R), and trans-signaling via a naturally occurring soluble IL-6R. To identify whether IL-6 trans-signaling and/or classical signaling contribute to the pathogenesis of emphysema. We used the gp130 F/F genetic mouse model for spontaneous emphysema and cigarette smoke-induced emphysema models. Emphysema in mice was quantified by various methods including in vivo lung function and stereology, and terminal deoxynucleotidyl transferase dUTP nick end labeling assay was used to assess alveolar cell apoptosis. In mouse and human lung tissues, the expression level and location of IL-6 signaling-related genes and proteins were measured, and the levels of IL-6 and related proteins in sera from emphysematous mice and patients were also assessed. Lung tissues from patients with emphysema, and from spontaneous and cigarette smoke-induced emphysema mouse models, were characterized by excessive production of soluble IL-6R. Genetic blockade of IL-6 trans-signaling in emphysema mouse models and therapy with the IL-6 trans-signaling antagonist sgp130Fc ameliorated emphysema by suppressing augmented alveolar type II cell apoptosis. Furthermore, IL-6 trans-signaling-driven emphysematous changes in the lung correlated with mechanistic target of rapamycin complex 1 hyperactivation, and treatment of emphysema mouse models with the mechanistic target of rapamycin complex 1 inhibitor rapamycin attenuated emphysematous changes. Collectively, our data reveal that specific targeting of IL-6 trans-signaling may represent a novel treatment strategy for emphysema.

Tritium pollution in the Swiss luminous compound industry

International Nuclear Information System (INIS)

Krejci, K.; Zeller, Jr.

1979-01-01

The Swiss luminous compound industry is an important consumer of tritium. About 350kCi go into production of tritium gas-filled light sources and 40kCi into production of tritium luminous compound annually. To illustrate the pollution problem, a factory is mentioned that handles 200kCi annually and a chain of luminizers, processing 20kCi over the same period as tritium luminous compound. This material is manufactured by coating phosphors with tritiated polystyrene having a specific activity up to 200Ci/g. Because of the high specific activity, the radiation damage produces an average activity release of 5.2% annually, which is one of the main reasons for public and occupational exposure. The processing of large quantities of tritium gas requires special equipment, such as units made entirely of stainless steel for purification and hydrogenation, oxidation systems for highly contaminated air, glove boxes, ventilation and monitoring systems. Nevertheless, contamination of air, surfaces, water and workers cannot be avoided. Only in a few cases were MPC-values for tritium content in urine of workers exceeded. From these results, biological half-lives between 5-15 days were estimated. Regular medical examinations showed no significant influence in blood picture parameters, except in one single case with a tritium concentration in urine of 2.8mCi/litre. Entirely different problems arise in most luminizing factories where luminous paint is processed as an open radioactive source. (author)

Arcing and rf signal generation during target irradiation by a high-energy, pulsed neutral particle beam

International Nuclear Information System (INIS)

Robiscoe, R.T.

1988-02-01

We present a theory describing the dynamics of arc discharges in bulk dielectric materials on board space-based vehicles. Such ''punch-through'' arcs can occur in target satellites irradiated by high-energy (250 MeV), pulsed (100 mA x 10 ms) neutral particle beams. We treat the arc as a capacitively limited avalanche current in the target dielectric material, and we find expressions for the arc duration, charge transport, currents, and discharge energy. These quantities are adjusted to be consistent with known scaling laws for the area of charge depleted by the arc. After a brief account of the statistical distribution of voltages at which the arc starts and stops, we calculate the signal strength and frequency spectrum of the electromagnetic radiation broadcast by the arc. We find that arcs from thick (/similar to/1 cm) targets can generate rf signals detectable up to 1000 km from the target, bu a radio receiver operating at frequency 80 MHz, bandwidth 100 kHz, and detection threshold -105 dBm. These thick-target arc signals are 10 to 20 dB above ambient noise at the receiver, and they provide target hit assessment if the signal spectrum can be sampled at several frequencies in the nominal range 30-200 MHz. Thin-target (/similar to/1 mm) arc signals are much weaker, but when they are detecable in conjunction with thick-target signals, target discrimination is possible by comparing the signal frequency spectra. 24 refs., 12 figs

The role of luminance and chromatic cues in emmetropisation.

Science.gov (United States)

Rucker, Frances J

2013-05-01

At birth most, but not all eyes, are hyperopic. Over the course of the first few years of life the refraction gradually becomes close to zero through a process called emmetropisation. This process is not thought to require accommodation, though a lag of accommodation has been implicated in myopia development, suggesting that the accuracy of accommodation is an important factor. This review will cover research on accommodation and emmetropisation that relates to the ability of the eye to use colour and luminance cues to guide the responses. There are three ways in which changes in luminance and colour contrast could provide cues: (1) The eye could maximize luminance contrast. Monochromatic light experiments have shown that the human eye can accommodate and animal eyes can emmetropise using changes in luminance contrast alone. However, by reducing the effectiveness of luminance cues in monochromatic and white light by introducing astigmatism, or by reducing light intensity, investigators have revealed that the eye also uses colour cues in emmetropisation. (2) The eye could compare relative cone contrast to derive the sign of defocus information from colour cues. Experiments involving simulations of the retinal image with defocus have shown that relative cone contrast can provide colour cues for defocus in accommodation and emmetropisation. In the myopic simulation the contrast of the red component of a sinusoidal grating was higher than that of the green and blue component and this caused relaxation of accommodation and reduced eye growth. In the hyperopic simulation the contrast of the blue component was higher than that of the green and red components and this caused increased accommodation and increased eye growth. (3) The eye could compare the change in luminance and colour contrast as the eye changes focus. An experiment has shown that changes in colour or luminance contrast can provide cues for defocus in emmetropisation. When the eye is exposed to colour

Cosmological information in the intrinsic alignments of luminous red galaxies

Energy Technology Data Exchange (ETDEWEB)

Chisari, Nora Elisa [Department of Astrophysical Sciences, Princeton University, 4 Ivy Lane, Princeton, NJ 08544 (United States); Dvorkin, Cora, E-mail: nchisari@astro.princeton.edu, E-mail: cdvorkin@ias.edu [Institute for Advanced Study, School of Natural Sciences, Einstein Drive, Princeton, NJ 08540 (United States)

2013-12-01

The intrinsic alignments of galaxies are usually regarded as a contaminant to weak gravitational lensing observables. The alignment of Luminous Red Galaxies, detected unambiguously in observations from the Sloan Digital Sky Survey, can be reproduced by the linear tidal alignment model of Catelan, Kamionkowski and Blandford (2001) on large scales. In this work, we explore the cosmological information encoded in the intrinsic alignments of red galaxies. We make forecasts for the ability of current and future spectroscopic surveys to constrain local primordial non-Gaussianity and Baryon Acoustic Oscillations (BAO) in the cross-correlation function of intrinsic alignments and the galaxy density field. For the Baryon Oscillation Spectroscopic Survey, we find that the BAO signal in the intrinsic alignments is marginally significant with a signal-to-noise ratio of 1.8 and 2.2 with the current LOWZ and CMASS samples of galaxies, respectively, and increasing to 2.3 and 2.7 once the survey is completed. For the Dark Energy Spectroscopic Instrument and for a spectroscopic survey following the EUCLID redshift selection function, we find signal-to-noise ratios of 12 and 15, respectively. Local type primordial non-Gaussianity, parametrized by f{sub NL} = 10, is only marginally significant in the intrinsic alignments signal with signal-to-noise ratios < 2 for the three surveys considered.

The effect of chromatic and luminance information on reaction times.

Science.gov (United States)

O'Donell, Beatriz M; Barraza, Jose F; Colombo, Elisa M

2010-07-01

We present a series of experiments exploring the effect of chromaticity on reaction time (RT) for a variety of stimulus conditions, including chromatic and luminance contrast, luminance, and size. The chromaticity of these stimuli was varied along a series of vectors in color space that included the two chromatic-opponent-cone axes, a red-green (L-M) axis and a blue-yellow [S - (L + M)] axis, and intermediate noncardinal orientations, as well as the luminance axis (L + M). For Weber luminance contrasts above 10-20%, RTs tend to the same asymptote, irrespective of chromatic direction. At lower luminance contrast, the addition of chromatic information shortens the RT. RTs are strongly influenced by stimulus size when the chromatic stimulus is modulated along the [S - (L + M)] pathway and by stimulus size and adaptation luminance for the (L-M) pathway. RTs are independent of stimulus size for stimuli larger than 0.5 deg. Data are modeled with a modified version of Pieron's formula with an exponent close to 2, in which the stimulus intensity term is replaced by a factor that considers the relative effects of chromatic and achromatic information, as indexed by the RMS (square-root of the cone contrast) value at isoluminance and the Weber luminance contrast, respectively. The parameters of the model reveal how RT is linked to stimulus size, chromatic channels, and adaptation luminance and how they can be interpreted in terms of two chromatic mechanisms. This equation predicts that, for isoluminance, RTs for a stimulus lying on the S-cone pathway are higher than those for a stimulus lying on the L-M-cone pathway, for a given RMS cone contrast. The equation also predicts an asymptotic trend to the RT for an achromatic stimulus when the luminance contrast is sufficiently large.

New method to extract radial acceleration of target from short-duration signal at low SNR

Institute of Scientific and Technical Information of China (English)

2008-01-01

In order to extract target radial acceleration from radar echo signal at low SNR (signal-to-noise), this paper employed FRFT (fractional Fourier transformation) to analyze short-duration radar echo and studied the relations between signal convergence peaks in matched transformation domain and signal duration and modu- lated frequency of signal. When signal duration is specified, the method of multi- plying sampled signal by the known frequency modulated signal to alter modulated frequency was presented, which generated the new signal with larger convergence peaks than the initial signal in matched transformation domain. Thus, it could successfully estimate the radial acceleration of radar target at low SNR. Simulations were conducted to show the feasibility and effectiveness of the method.

Ganoderma lucidum targeting lung cancer signaling: A review.

Science.gov (United States)

Gill, Balraj Singh; Navgeet; Kumar, Sanjeev

2017-06-01

Lung cancer causes huge mortality to population, and pharmaceutical companies require new drugs as an alternative either synthetic or natural targeting lung cancer. The conventional therapies cause side effects, and therefore, natural products are used as a therapeutic candidate in lung cancer. Chemical diversity among natural products highlights the impact of evolution and survival of fittest. One such neglected natural product is Ganoderma lucidum used for promoting health and longevity for a longer time. The major bioconstituents of G. lucidum are mainly terpenes, polysaccharides, and proteins, which were explored for various activities ranging from apoptosis to autophagy. The bioconstituents of G. lucidum activate plasma membrane receptors and initiate various downstream signaling leading to nuclear factor-κB, phosphoinositide 3-kinase, Akt, and mammalian target of rapamycin in cancer. The bioconstituents regulate the expression of various genes involved in cell cycle, immune response, apoptosis, and autophagy in lung cancer. This review highlights the inextricable role of G. lucidum and its bioconstituents in lung cancer signaling for the first time.

Fractal properties of background noise and target signal enhancement using CSEM data

Science.gov (United States)

Benavides, Alfonso; Everett, Mark E.; Pierce, Carl; Nguyen, Cam

2003-09-01

Controlled-source electromagnetic (CSEM) spatial profiles and 2-D conductivity maps were obtained on the Brazos Valley, TX floodplain to study the fractal statistics of geological signals and effects of man-made conductive targets using Geonics EM34, EM31 and EM63. Using target-free areas, a consistent power-law power spectrum (|A(k)| ~ k ^-β) for the profiles was found with β values typical of fractional Brownian motion (fBm). This means that the spatial variation of conductivity does not correspond to Gaussian statistics, where there are spatial correlations at different scales. The presence of targets tends to flatten the power-law power spectrum (PS) at small wavenumbers. Detection and localization of targets can be achieved using short-time Fourier transform (STFT). The presence of targets is enhanced because the signal energy is spread to higher wavenumbers (small scale numbers) in the positions occupied by the targets. In the case of poor spatial sampling or small amount of data, the information available from the power spectrum is not enough to separate spatial correlations from target signatures. Advantages are gained by using the spatial correlations of the fBm in order to reject the background response, and to enhance the signals from highly conductive targets. This approach was tested for the EM31 using a pre-processing step that combines apparent conductivity readings from two perpendicular transmitter-receiver orientations at each station. The response obtained using time-domain CSEM is influence to a lesser degree by geological noise and the target response can be processed to recover target features. The homotopy method is proposed to solve the inverse problem using a set of possible target models and a dynamic library of responses used to optimize the starting model.

Month-hour distributions of zenith luminance and diffuse illuminance in Madrid

International Nuclear Information System (INIS)

Soler, Alfonso; Gopinathan, Kannam K.; Robledo, Luis; Ruiz, Enrique

2004-01-01

Month-hour equal mean zenith luminance contours are obtained from one year of data of zenith luminance measurements for cloudless, overcast and partly cloudy skies and also when the combined data for all sky types are considered. For many hours in different months, the overcast sky luminance values are roughly about three times the cloudless sky luminance values and one and a half times the partly cloudy sky values. The dependence of month-hour equal mean zenith luminance contours on the ratio of global to extraterrestrial illuminance on a horizontal surface is also given. From equal mean zenith luminance contours, the approximate values of the mean zenith luminance for different sky conditions and different hours and months of the year can be easily obtained. Month-hour equal mean diffuse illuminance contours are obtained from diffuse illuminance measurements performed during the period 1992-1998. The dependence on solar altitude of the monthly average hourly values of diffuse illuminance is given and compared to the corresponding one obtained from data for Bet Dagan (Israel)

Effects of Irradiation on bacterial atp luminous intensity of cooled pork and chicken

International Nuclear Information System (INIS)

Ju Hua

2010-01-01

The effect of irradiation on cooled pork and chicken was detected with ATP luminous intensity method. The influences of other factors to ATP luminous intensity were also discussed. There was positive correlation between ATP standard concentration and ATP luminous intensity, and negative correlation between irradiation dosage and ATP luminous intensity. The trend of ATP luminous intensity of cooled pork and chicken after irradiation was inverse S, and the maximum ATP luminous intensity appeared at 6.0 kGy, and minimum at 4.0 and 8.0 kGy. Sterilized water and sterilized pork had no interference to ATP luminous intensity of the samples. There was significant positive correlation between E. coli 10003 concentration and ATP luminous intensity, the coefficient correlation was 0.9437. (authors)

Luminance-based specular gloss characterization.

Science.gov (United States)

Leloup, Frédéric B; Pointer, Michael R; Dutré, Philip; Hanselaer, Peter

2011-06-01

Gloss is a feature of visual appearance that arises from the directionally selective reflection of light incident on a surface. Especially when a distinct reflected image is perceptible, the luminance distribution of the illumination scene above the sample can strongly influence the gloss perception. For this reason, industrial glossmeters do not provide a satisfactory gloss estimation of high-gloss surfaces. In this study, the influence of the conditions of illumination on specular gloss perception was examined through a magnitude estimation experiment in which 10 observers took part. A light booth with two light sources was utilized: the mirror image of only one source being visible in reflection by the observer. The luminance of both the reflected image and the adjacent sample surface could be independently varied by separate adjustment of the intensity of the two light sources. A psychophysical scaling function was derived, relating the visual gloss estimations to the measured luminance of both the reflected image and the off-specular sample background. The generalization error of the model was estimated through a validation experiment performed by 10 other observers. In result, a metric including both surface and illumination properties is provided. Based on this metric, improved gloss evaluation methods and instruments could be developed.

Delineating neurotrophin-3 dependent signaling pathways underlying sympathetic axon growth along intermediate targets.

Science.gov (United States)

Keeler, Austin B; Suo, Dong; Park, Juyeon; Deppmann, Christopher D

2017-07-01

Postganglionic sympathetic neurons detect vascular derived neurotrophin 3 (NT3) via the axonally expressed receptor tyrosine kinase, TrkA, to promote chemo-attraction along intermediate targets. Once axons arrive to their final target, a structurally related neurotrophic factor, nerve growth factor (NGF), also acts through TrkA to promote final target innervation. Does TrkA signal differently at these different locales? We previously found that Coronin-1 is upregulated in sympathetic neurons upon exposure to NGF, thereby endowing the NGF-TrkA complex with new signaling capabilities (i.e. calcium signaling), which dampens axon growth and branching. Based on the notion that axons do not express functional levels of Coronin-1 prior to final target innervation, we developed an in vitro model for axon growth and branching along intermediate targets using Coro1a -/- neurons grown in NT3. We found that, similar to NGF-TrkA, NT3-TrkA is capable of inducing MAPK and PI3K in the presence or absence of Coronin-1. However, unlike NGF, NT3 does not induce calcium release from intracellular stores. Using a combination of pharmacology, knockout neurons and in vitro functional assays, we suggest that the NT3-TrkA complex uses Ras/MAPK and/or PI3K-AKT signaling to induce axon growth and inhibit axon branching along intermediate targets. However, in the presence of Coronin-1, these signaling pathways lose their ability to impact NT3 dependent axon growth or branching. This is consistent with a role for Coronin-1 as a molecular switch for axon behavior and suggests that Coronin-1 suppresses NT3 dependent axon behavior. Copyright © 2017 Elsevier Inc. All rights reserved.

Targeting fibroblast growth factor receptor signaling inhibits prostate cancer progression.

Science.gov (United States)

Feng, Shu; Shao, Longjiang; Yu, Wendong; Gavine, Paul; Ittmann, Michael

2012-07-15

Extensive correlative studies in human prostate cancer as well as studies in vitro and in mouse models indicate that fibroblast growth factor receptor (FGFR) signaling plays an important role in prostate cancer progression. In this study, we used a probe compound for an FGFR inhibitor, which potently inhibits FGFR-1-3 and significantly inhibits FGFR-4. The purpose of this study is to determine whether targeting FGFR signaling from all four FGFRs will have in vitro activities consistent with inhibition of tumor progression and will inhibit tumor progression in vivo. Effects of AZ8010 on FGFR signaling and invasion were analyzed using immortalized normal prostate epithelial (PNT1a) cells and PNT1a overexpressing FGFR-1 or FGFR-4. The effect of AZ8010 on invasion and proliferation in vitro was also evaluated in prostate cancer cell lines. Finally, the impact of AZ8010 on tumor progression in vivo was evaluated using a VCaP xenograft model. AZ8010 completely inhibits FGFR-1 and significantly inhibits FGFR-4 signaling at 100 nmol/L, which is an achievable in vivo concentration. This results in marked inhibition of extracellular signal-regulated kinase (ERK) phosphorylation and invasion in PNT1a cells expressing FGFR-1 and FGFR-4 and all prostate cancer cell lines tested. Treatment in vivo completely inhibited VCaP tumor growth and significantly inhibited angiogenesis and proliferation and increased cell death in treated tumors. This was associated with marked inhibition of ERK phosphorylation in treated tumors. Targeting FGFR signaling is a promising new approach to treating aggressive prostate cancer.

Chromatic signals control proboscis movements during hovering flight in the hummingbird hawkmoth Macroglossum stellatarum.

Science.gov (United States)

Goyret, Joaquín; Kelber, Almut

2012-01-01

Most visual systems are more sensitive to luminance than to colour signals. Animals resolve finer spatial detail and temporal changes through achromatic signals than through chromatic ones. Probably, this explains that detection of small, distant, or moving objects is typically mediated through achromatic signals. Macroglossum stellatarum are fast flying nectarivorous hawkmoths that inspect flowers with their long proboscis while hovering. They can visually control this behaviour using floral markings known as nectar guides. Here, we investigate whether this is mediated by chromatic or achromatic cues. We evaluated proboscis placement, foraging efficiency, and inspection learning of naïve moths foraging on flower models with coloured markings that offered either chromatic, achromatic or both contrasts. Hummingbird hawkmoths could use either achromatic or chromatic signals to inspect models while hovering. We identified three, apparently independent, components controlling proboscis placement: After initial contact, 1) moths directed their probing towards the yellow colour irrespectively of luminance signals, suggesting a dominant role of chromatic signals; and 2) moths tended to probe mainly on the brighter areas of models that offered only achromatic signals. 3) During the establishment of the first contact, naïve moths showed a tendency to direct their proboscis towards the small floral marks independent of their colour or luminance. Moths learned to find nectar faster, but their foraging efficiency depended on the flower model they foraged on. Our results imply that M. stellatarum can perceive small patterns through colour vision. We discuss how the different informational contents of chromatic and luminance signals can be significant for the control of flower inspection, and visually guided behaviours in general.

Detection of chromatic and luminance distortions in natural scenes.

Science.gov (United States)

Jennings, Ben J; Wang, Karen; Menzies, Samantha; Kingdom, Frederick A A

2015-09-01

A number of studies have measured visual thresholds for detecting spatial distortions applied to images of natural scenes. In one study, Bex [J. Vis.10(2), 1 (2010)10.1167/10.2.231534-7362] measured sensitivity to sinusoidal spatial modulations of image scale. Here, we measure sensitivity to sinusoidal scale distortions applied to the chromatic, luminance, or both layers of natural scene images. We first established that sensitivity does not depend on whether the undistorted comparison image was of the same or of a different scene. Next, we found that, when the luminance but not chromatic layer was distorted, performance was the same regardless of whether the chromatic layer was present, absent, or phase-scrambled; in other words, the chromatic layer, in whatever form, did not affect sensitivity to the luminance layer distortion. However, when the chromatic layer was distorted, sensitivity was higher when the luminance layer was intact compared to when absent or phase-scrambled. These detection threshold results complement the appearance of periodic distortions of the image scale: when the luminance layer is distorted visibly, the scene appears distorted, but when the chromatic layer is distorted visibly, there is little apparent scene distortion. We conclude that (a) observers have a built-in sense of how a normal image of a natural scene should appear, and (b) the detection of distortion in, as well as the apparent distortion of, natural scene images is mediated predominantly by the luminance layer and not chromatic layer.

Application of radioisotope for radio-luminous watch and clock industry in Japan

International Nuclear Information System (INIS)

Murayama, Yoshihiko

1981-01-01

In 1979, Japan became No. 1 watch and clock production country in the world, and has produced 88 million watches and 59 million clocks in 1980. About 65% of them were exported. The production of radio-luminous watches and clocks in 1980 was estimated as 13 million and 11 million, respectively, and has increased by 40% as compared with the previous year. In Japan, the law concerning the prevention of radiation injuries due to radioisotopes and others is applied to radio-luminous watches and clocks, because radioactive substances are contained in luminous paint, and the production is regulated by the law as unsealed RI-using establishments. The permitted establishments engaging in radio-luminous watches and clocks are 3 luminous paint makers, 9 painting works and 35 watch and clock assembling plants. The RI utilized for radio-luminous watches and clocks is limited to Pm-147 at present, and 3788 Ci was used in 1980. About 70 years have elapsed since luminous paint was used for watches and clocks for the first time. The ISO instituted the international standard on radio-luminous paint for watches and clocks in 1975. The beta-ray emitted by Pm-147 is shielded perfectly by glasses and cases, and only the dose of brems-strahlung X-ray is the problem. The radiation control in radio-luminous watch and clock plants is described. (Kako, I.)

Impact of Intestinal Microbiota on Intestinal Luminal Metabolome

Science.gov (United States)

Matsumoto, Mitsuharu; Kibe, Ryoko; Ooga, Takushi; Aiba, Yuji; Kurihara, Shin; Sawaki, Emiko; Koga, Yasuhiro; Benno, Yoshimi

2012-01-01

Low–molecular-weight metabolites produced by intestinal microbiota play a direct role in health and disease. In this study, we analyzed the colonic luminal metabolome using capillary electrophoresis mass spectrometry with time-of-flight (CE-TOFMS) —a novel technique for analyzing and differentially displaying metabolic profiles— in order to clarify the metabolite profiles in the intestinal lumen. CE-TOFMS identified 179 metabolites from the colonic luminal metabolome and 48 metabolites were present in significantly higher concentrations and/or incidence in the germ-free (GF) mice than in the Ex-GF mice (p metabolome and a comprehensive understanding of intestinal luminal metabolome is critical for clarifying host-intestinal bacterial interactions. PMID:22724057

TRAIL, Wnt, Sonic Hedgehog, TGFβ, and miRNA Signalings Are Potential Targets for Oral Cancer Therapy.

Science.gov (United States)

Farooqi, Ammad Ahmad; Shu, Chih-Wen; Huang, Hurng-Wern; Wang, Hui-Ru; Chang, Yung-Ting; Fayyaz, Sundas; Yuan, Shyng-Shiou F; Tang, Jen-Yang; Chang, Hsueh-Wei

2017-07-14

Clinical studies and cancer cell models emphasize the importance of targeting therapies for oral cancer. The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is highly expressed in cancer, and is a selective killing ligand for oral cancer. Signaling proteins in the wingless-type mouse mammary tumor virus (MMTV) integration site family (Wnt), Sonic hedgehog (SHH), and transforming growth factor β (TGFβ) pathways may regulate cell proliferation, migration, and apoptosis. Accordingly, the genes encoding these signaling proteins are potential targets for oral cancer therapy. In this review, we focus on recent advances in targeting therapies for oral cancer and discuss the gene targets within TRAIL, Wnt, SHH, and TGFβ signaling for oral cancer therapies. Oncogenic microRNAs (miRNAs) and tumor suppressor miRNAs targeting the genes encoding these signaling proteins are summarized, and the interactions between Wnt, SHH, TGFβ, and miRNAs are interpreted. With suitable combination treatments, synergistic effects are expected to improve targeting therapies for oral cancer.

TRAIL, Wnt, Sonic Hedgehog, TGFβ, and miRNA Signalings Are Potential Targets for Oral Cancer Therapy

Science.gov (United States)

Farooqi, Ammad Ahmad; Shu, Chih-Wen; Huang, Hurng-Wern; Wang, Hui-Ru; Chang, Yung-Ting; Fayyaz, Sundas; Yuan, Shyng-Shiou F.; Tang, Jen-Yang

2017-01-01

Clinical studies and cancer cell models emphasize the importance of targeting therapies for oral cancer. The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is highly expressed in cancer, and is a selective killing ligand for oral cancer. Signaling proteins in the wingless-type mouse mammary tumor virus (MMTV) integration site family (Wnt), Sonic hedgehog (SHH), and transforming growth factor β (TGFβ) pathways may regulate cell proliferation, migration, and apoptosis. Accordingly, the genes encoding these signaling proteins are potential targets for oral cancer therapy. In this review, we focus on recent advances in targeting therapies for oral cancer and discuss the gene targets within TRAIL, Wnt, SHH, and TGFβ signaling for oral cancer therapies. Oncogenic microRNAs (miRNAs) and tumor suppressor miRNAs targeting the genes encoding these signaling proteins are summarized, and the interactions between Wnt, SHH, TGFβ, and miRNAs are interpreted. With suitable combination treatments, synergistic effects are expected to improve targeting therapies for oral cancer. PMID:28708091

Targeting embryonic signaling pathways in cancer therapy.

Science.gov (United States)

Harris, Pamela Jo; Speranza, Giovanna; Dansky Ullmann, Claudio

2012-01-01

The embryonic signaling pathways (ESP), Hedgehog, Notch and Wnt, are critical for the regulation of normal stem cells and cellular development processes. They are also activated in the majority of cancers. ESP are operational in putative cancer stem cells (CSC), which drive initial tumorigenesis and sustain cancer progression and recurrence in non-CSC bulk subpopulations. ESP represent novel therapeutic targets. A variety of inhibitors and targeting strategies are being developed. This review discusses the rationale for targeting ESP for cancer treatment, as well as specific inhibitors under development; mainly focusing on those approaching clinical use and the challenges that lie ahead. The data sources utilized are several database search engines (PubMed, Google, Clinicaltrials.gov), and the authors' involvement in the field. CSC research is rapidly evolving. Expectations regarding their therapeutic targeting are rising quickly. Further definition of what constitutes a true CSC, proper validation of CSC markers, a better understanding of cross-talk among ESP and other pathways, and interactions with tumor non-CSC and the tumor microenvironment are needed. The appropriate patient population, the right clinical setting and combination strategies to test these therapies, as well as the proper pharmacodynamic markers to measure, need to be further established.

Advancing Our Understanding of the Etiologies and Mutational Landscapes of Basal Like, Luminal A, and Luminal B Breast Cancers

Science.gov (United States)

2016-10-01

will be further analyzed for effects on reading frame and protein structure and function using analysis and prediction tools such as PolyPhen and...luminal A, and luminal B tumors. Originally this study intended to include 900 newly diagnosed first primary triple negative (TN) invasive breast cancer...breast cancer risk factors. At the end of the interview participants will be asked to donate an oral tissue specimen for future genetic testing. Medical

Rac1 in human diseases: The therapeutic potential of targeting Rac1 signaling regulatory mechanisms.

Science.gov (United States)

Marei, Hadir; Malliri, Angeliki

2017-07-03

Abnormal Rac1 signaling is linked to a number of debilitating human diseases, including cancer, cardiovascular diseases and neurodegenerative disorders. As such, Rac1 represents an attractive therapeutic target, yet the search for effective Rac1 inhibitors is still underway. Given the adverse effects associated with Rac1 signaling perturbation, cells have evolved several mechanisms to ensure the tight regulation of Rac1 signaling. Thus, characterizing these mechanisms can provide invaluable information regarding major cellular events that lead to aberrant Rac1 signaling. Importantly, this information can be utilized to further facilitate the development of effective pharmacological modulators that can restore normal Rac1 signaling. In this review, we focus on the pathological role of Rac1 signaling, highlighting the benefits and potential drawbacks of targeting Rac1 in a clinical setting. Additionally, we provide an overview of available compounds that target key Rac1 regulatory mechanisms and discuss future therapeutic avenues arising from our understanding of these mechanisms.

Influence of Al{sub 2}O{sub 3} reflective layer under phosphor layer on luminance and luminous efficiency characteristics in alternating-current plasma display panel

Energy Technology Data Exchange (ETDEWEB)

Park, Choon-Sang [School of Electronics Engineering, College of IT Engineering, Kyungpook National University, Daegu (Korea, Republic of); Tae, Heung-Sik, E-mail: hstae@ee.knu.ac.kr [School of Electronics Engineering, College of IT Engineering, Kyungpook National University, Daegu (Korea, Republic of); Jung, Eun Young [Core Technology Lab., Corporate R and D Center, Samsung SDI Company Ltd., Cheonan (Korea, Republic of)

2013-11-29

This paper examines the optical and discharge characteristics of alternating-current plasma display panel when adopting the Al{sub 2}O{sub 3} reflective layer. The Al{sub 2}O{sub 3} reflective layer is deposited under the phosphor layer by using the screen-printing method. The resulting changes in the optical and discharge characteristics, including the power consumption, color temperature, luminance, luminous efficiency, scanning electron microscopy image, and reflectance, are then compared for both cases with and without Al{sub 2}O{sub 3} reflective layer. As a result of optimizing the thicknesses between the Al{sub 2}O{sub 3} and phosphor layers, the luminance and luminous efficiency are improved by about 17% and 7%, respectively. - Highlights: • We examine characteristics of plasma display panel when adopting reflective layer. • Al{sub 2}O{sub 3} reflective layer was deposited under the phosphor layer. • Al{sub 2}O{sub 3} reflective layer with flaky shape is very effective in enhancing luminance.

Dynamics of backlight luminance for using smartphone in dark environment

Science.gov (United States)

Na, Nooree; Jang, Jiho; Suk, Hyeon-Jeong

2014-02-01

This study developed dynamic backlight luminance, which gradually changes as time passes for comfortable use of a smartphone display in a dark environment. The study was carried out in two stages. In the first stage, a user test was conducted to identify the optimal luminance by assessing the facial squint level, subjective glare evaluation, eye blink frequency and users' subjective preferences. Based on the results of the user test, the dynamics of backlight luminance was designed. It has two levels of luminance: the optimal level for initial viewing to avoid sudden glare or fatigue to users' eyes, and the optimal level for constant viewing, which is comfortable, but also bright enough for constant reading of the displayed material. The luminance for initial viewing starts from 10 cd/m2, and it gradually increases to 40 cd/m2 for users' visual comfort at constant viewing for 20 seconds; In the second stage, a validation test on dynamics of backlight luminance was conducted to verify the effectiveness of the developed dynamics. It involving users' subjective preferences, eye blink frequency, and brainwave analysis using the electroencephalogram (EEG) to confirm that the proposed dynamic backlighting enhances users' visual comfort and visual cognition, particularly for using smartphones in a dark environment.

Predicting daylight illuminance on inclined surfaces using sky luminance data

Energy Technology Data Exchange (ETDEWEB)

Li, D.H.W.; Lau, C.C.S.; Lam, J.C. [City University of Hong Kong, Kowloon (China). Dept. of Building and Construction

2005-07-01

Daylight illuminance, particularly on vertical surfaces, plays a major role in determining and evaluating the daylighting performance of a building. In many parts of the world, however, the basic daylight illuminance data for various vertical planes are not always readily available. The usual method to obtain diffuse illuminance on tilted planes would be based on inclined surface models using data from the horizontal measurements. Alternatively, the diffuse illuminance on a sloping plane can be computed by integrating the luminance distribution of the sky 'seen' by the plane. This paper presents an approach to estimate the vertical outdoor illuminance from sky luminance data and solar geometry. Sky luminance data recorded from January 1999 to December 2001 in Hong Kong and generated by two well-known sky luminance models (Kittler and Perez) were used to compute the outdoor illuminance for the four principal vertical planes (N, E, S and W). The performance of this approach was evaluated against data measured in the same period. Statistical analysis indicated that using sky luminance distributions to predict outdoor illuminance can give reasonably good agreement with measured data for all vertical surfaces. The findings provide an accurate alternative to determine the amount of daylight on vertical as well as other inclined surfaces when sky luminance data are available. (author)

Identification of the feedforward component in manual control with predictable target signals.

Science.gov (United States)

Drop, Frank M; Pool, Daan M; Damveld, Herman J; van Paassen, Marinus M; Mulder, Max

2013-12-01

In the manual control of a dynamic system, the human controller (HC) often follows a visible and predictable reference path. Compared with a purely feedback control strategy, performance can be improved by making use of this knowledge of the reference. The operator could effectively introduce feedforward control in conjunction with a feedback path to compensate for errors, as hypothesized in literature. However, feedforward behavior has never been identified from experimental data, nor have the hypothesized models been validated. This paper investigates human control behavior in pursuit tracking of a predictable reference signal while being perturbed by a quasi-random multisine disturbance signal. An experiment was done in which the relative strength of the target and disturbance signals were systematically varied. The anticipated changes in control behavior were studied by means of an ARX model analysis and by fitting three parametric HC models: two different feedback models and a combined feedforward and feedback model. The ARX analysis shows that the experiment participants employed control action on both the error and the target signal. The control action on the target was similar to the inverse of the system dynamics. Model fits show that this behavior can be modeled best by the combined feedforward and feedback model.

[Advanced luminal breast cancer (hormone receptor-positive, HER2 negative): New therapeutic options in 2015].

Science.gov (United States)

Vanacker, Hélène; Bally, Olivia; Kassem, Loay; Tredan, Olivier; Heudel, Pierre; Bachelot, Thomas

2015-06-01

Despite improvements in early detection, surgery and systemic therapy, metastatic breast cancer remains a major cause of death. Luminal type breast cancers expressing hormone estrogen receptor (ER) or progesterone (PR) and without HER2 overexpression are generally sensitive to endocrine therapy, but raise the issue of the occurrence of resistance to treatment, particularly at metastatic stage. A better understanding of hormone resistance may guide the development of new therapeutics. New strategies aim at enhancing and prolonging of endocrine sensitivity, by optimizing existing schemes, or by combining an endocrine therapy with a targeted therapies specific to hormone resistance pathways: ER signaling, PI3K/AKT/mTOR and Cyclin Dependent Kinase (CDK). Key corners of 2014 include confirmation of benefit of high dose fulvestrant, and commercialization of everolimus as the first mTOR inhibitor in this indication. Other strategies are being tested dealing with new endocrine therapies or new molecular targets such as PI3K inhibitors, insulin-like growth factor receptor (IGF-R) and histone deacetylase (HDAC) inhibitors. Coming years may be fruitful and might radically change our way to treat these patients. Copyright © 2015 Société Françise du Cancer. Publié par Elsevier Masson SAS. Tous droits réservés. Published by Elsevier Masson SAS. All rights reserved.

File list: His.Brs.10.AllAg.Luminal_cells [Chip-atlas[Archive

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File list: His.Brs.50.AllAg.Luminal_cells [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available His.Brs.50.AllAg.Luminal_cells mm9 Histone Breast Luminal cells SRX213395,SRX213418...,SRX213416 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Brs.50.AllAg.Luminal_cells.bed ...

Radiation exposure to dial painters from 3H luminous paint industry

International Nuclear Information System (INIS)

Sawant, J.V.

1992-01-01

Tritium is used as the active component in self-luminous paint. The paper describes in-vitro solubilisation study of luminous paint in blood serum. Besides urine samples of luminous paint workers and air samples of two watch factories were analysed for 3 H. The results of these analysis are also presented. (author). 8 refs., 4 figs., 4 tabs

mTOR Signaling Confers Resistance to Targeted Cancer Drugs.

Science.gov (United States)

Guri, Yakir; Hall, Michael N

2016-11-01

Cancer is a complex disease and a leading cause of death worldwide. Extensive research over decades has led to the development of therapies that target cancer-specific signaling pathways. However, the clinical benefits of such drugs are at best transient due to tumors displaying intrinsic or adaptive resistance. The underlying compensatory pathways that allow cancer cells to circumvent a drug blockade are poorly understood. We review here recent studies suggesting that mammalian TOR (mTOR) signaling is a major compensatory pathway conferring resistance to many cancer drugs. mTOR-mediated resistance can be cell-autonomous or non-cell-autonomous. These findings suggest that mTOR signaling should be monitored routinely in tumors and that an mTOR inhibitor should be considered as a co-therapy. Copyright © 2016 Elsevier Inc. All rights reserved.

THE UNUSUALLY LUMINOUS EXTRAGALACTIC NOVA SN 2010U

International Nuclear Information System (INIS)

Czekala, Ian; Berger, E.; Chornock, R.; Marion, G. H.; Margutti, R.; Challis, P.; Pastorello, A.; Botticella, M. T.; Ergon, M.; Sollerman, J.; Smartt, S.; Vinkó, J.; Wheeler, J. C.

2013-01-01

We present observations of the unusual optical transient SN 2010U, including spectra taken 1.03 days to 15.3 days after maximum light that identify it as a fast and luminous Fe II type nova. Our multi-band light curve traces the fast decline (t 2 = 3.5 ± 0.3 days) from maximum light (M V = –10.2 ± 0.1 mag), placing SN 2010U in the top 0.5% of the most luminous novae ever observed. We find typical ejecta velocities of ≈1100 km s –1 and that SN 2010U shares many spectral and photometric characteristics with two other fast and luminous Fe II type novae, including Nova LMC 1991 and M31N-2007-11d. For the extreme luminosity of this nova, the maximum magnitude versus rate of decline relationship indicates a massive white dwarf (WD) progenitor with a low pre-outburst accretion rate. However, this prediction is in conflict with emerging theories of nova populations, which predict that luminous novae from massive WDs should preferentially exhibit an alternate spectral type (He/N) near maximum light.

File list: ALL.Brs.10.AllAg.Luminal_cells [Chip-atlas[Archive

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File list: ALL.Brs.20.AllAg.Luminal_cells [Chip-atlas[Archive

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Astronomy. ASASSN-15lh: A highly super-luminous supernova.

Science.gov (United States)

Dong, Subo; Shappee, B J; Prieto, J L; Jha, S W; Stanek, K Z; Holoien, T W-S; Kochanek, C S; Thompson, T A; Morrell, N; Thompson, I B; Basu, U; Beacom, J F; Bersier, D; Brimacombe, J; Brown, J S; Bufano, F; Chen, Ping; Conseil, E; Danilet, A B; Falco, E; Grupe, D; Kiyota, S; Masi, G; Nicholls, B; Olivares E, F; Pignata, G; Pojmanski, G; Simonian, G V; Szczygiel, D M; Woźniak, P R

2016-01-15

We report the discovery of ASASSN-15lh (SN 2015L), which we interpret as the most luminous supernova yet found. At redshift z = 0.2326, ASASSN-15lh reached an absolute magnitude of Mu ,AB = -23.5 ± 0.1 and bolometric luminosity Lbol = (2.2 ± 0.2) × 10(45) ergs s(-1), which is more than twice as luminous as any previously known supernova. It has several major features characteristic of the hydrogen-poor super-luminous supernovae (SLSNe-I), whose energy sources and progenitors are currently poorly understood. In contrast to most previously known SLSNe-I that reside in star-forming dwarf galaxies, ASASSN-15lh appears to be hosted by a luminous galaxy (MK ≈ -25.5) with little star formation. In the 4 months since first detection, ASASSN-15lh radiated (1.1 ± 0.2) × 10(52) ergs, challenging the magnetar model for its engine. Copyright © 2016, American Association for the Advancement of Science.

Independence and interaction of luminance and chromatic contributions to spatial hyperacuity performance.

Science.gov (United States)

Cooper, Bonnie; Lee, Barry B

2014-04-01

Here we test interactions of luminance and chromatic input to spatial hyperacuity mechanisms. First, we tested alignment of luminance and chromatic gratings matched or mismatched in contrast polarity or grating type. Thresholds with matched gratings were low while all mismatched pairs were elevated. Second, we determined alignment acuity as a function of luminance or chromatic contrast alone or in the presence of constant contrast components of the other type. For in-phase components, performance followed the envelope of the more sensitive mechanism. However, polarity reversals revealed an asymmetric effect for luminance and chromatic conditions, which suggested that luminance can override chromatic mechanisms in hyperacuity; we interpret these findings in the context of spatial mechanisms.

MRI texture analysis in differentiating luminal A and luminal B breast cancer molecular subtypes - a feasibility study.

Science.gov (United States)

Holli-Helenius, Kirsi; Salminen, Annukka; Rinta-Kiikka, Irina; Koskivuo, Ilkka; Brück, Nina; Boström, Pia; Parkkola, Riitta

2017-12-29

The aim of this study was to use texture analysis (TA) of breast magnetic resonance (MR) images to assist in differentiating estrogen receptor (ER) positive breast cancer molecular subtypes. Twenty-seven patients with histopathologically proven invasive ductal breast cancer were selected in preliminary study. Tumors were classified into molecular subtypes: luminal A (ER-positive and/or progesterone receptor (PR)-positive, human epidermal growth factor receptor type 2 (HER2) -negative, proliferation marker Ki-67 MaZda. Texture parameters and tumour volumes were correlated with tumour prognostic factors. Textural differences were observed mainly in precontrast images. The two most discriminative texture parameters to differentiate luminal A and luminal B subtypes were sum entropy and sum variance (p = 0.003). The AUCs were 0.828 for sum entropy (p = 0.004), and 0.833 for sum variance (p = 0.003), and 0.878 for the model combining texture features sum entropy, sum variance (p = 0.001). In the LOOCV, the AUC for model combining features sum entropy and sum variance was 0.876. Sum entropy and sum variance showed positive correlation with higher Ki-67 index. Luminal B types were larger in volume and moderate correlation between larger tumour volume and higher Ki-67 index was also observed (r = 0.499, p = 0.008). Texture features which measure randomness, heterogeneity or smoothness and homogeneity may either directly or indirectly reflect underlying growth patterns of breast tumours. TA and volumetric analysis may provide a way to evaluate the biologic aggressiveness of breast tumours and provide aid in decisions regarding therapeutic efficacy.

Study on the luminous characteristics of a natural ball lightning

Science.gov (United States)

Wang, Hao; Yuan, Ping; Cen, Jianyong; Liu, Guorong

2018-02-01

According to the optical images of the whole process of a natural ball lightning recorded by two slit-less spectrographs in the Qinghai plateau of China, the simulated observation experiment on the luminous intensity of the spherical light source was carried out. The luminous intensity and the optical power of the natural ball lightning in the wavelength range of 400-690 nm were estimated based on the experimental data and the Lambert-Beer Law. The results show that the maximum luminous intensity was about 1.24 × 105 cd in the initial stage of the natural ball lightning, and the maximum luminous intensity and the maximum optical power in most time of its life were about 5.9 × 104 cd and 4.2 × 103 W, respectively.

Ecology and biology of luminous bacteria in the Arabian Sea

Digital Repository Service at National Institute of Oceanography (India)

Ramaiah, N.; Chandramohan, D.

Extensive studies on occurrence, distribution and species composition of luminous bacteria in the Arabian Sea were carried out from various habitats. Luminous bacterial population was by far the highest in the environs of the Arabian Sea...

Candidate luminal B breast cancer genes identified by genome, gene expression and DNA methylation profiling.

Directory of Open Access Journals (Sweden)

Stéphanie Cornen

Full Text Available Breast cancers (BCs of the luminal B subtype are estrogen receptor-positive (ER+, highly proliferative, resistant to standard therapies and have a poor prognosis. To better understand this subtype we compared DNA copy number aberrations (CNAs, DNA promoter methylation, gene expression profiles, and somatic mutations in nine selected genes, in 32 luminal B tumors with those observed in 156 BCs of the other molecular subtypes. Frequent CNAs included 8p11-p12 and 11q13.1-q13.2 amplifications, 7q11.22-q34, 8q21.12-q24.23, 12p12.3-p13.1, 12q13.11-q24.11, 14q21.1-q23.1, 17q11.1-q25.1, 20q11.23-q13.33 gains and 6q14.1-q24.2, 9p21.3-p24,3, 9q21.2, 18p11.31-p11.32 losses. A total of 237 and 101 luminal B-specific candidate oncogenes and tumor suppressor genes (TSGs presented a deregulated expression in relation with their CNAs, including 11 genes previously reported associated with endocrine resistance. Interestingly, 88% of the potential TSGs are located within chromosome arm 6q, and seven candidate oncogenes are potential therapeutic targets. A total of 100 candidate oncogenes were validated in a public series of 5,765 BCs and the overexpression of 67 of these was associated with poor survival in luminal tumors. Twenty-four genes presented a deregulated expression in relation with a high DNA methylation level. FOXO3, PIK3CA and TP53 were the most frequent mutated genes among the nine tested. In a meta-analysis of next-generation sequencing data in 875 BCs, KCNB2 mutations were associated with luminal B cases while candidate TSGs MDN1 (6q15 and UTRN (6q24, were mutated in this subtype. In conclusion, we have reported luminal B candidate genes that may play a role in the development and/or hormone resistance of this aggressive subtype.

Synergistic target combination prediction from curated signaling networks: Machine learning meets systems biology and pharmacology.

Science.gov (United States)

Chua, Huey Eng; Bhowmick, Sourav S; Tucker-Kellogg, Lisa

2017-10-01

Given a signaling network, the target combination prediction problem aims to predict efficacious and safe target combinations for combination therapy. State-of-the-art in silico methods use Monte Carlo simulated annealing (mcsa) to modify a candidate solution stochastically, and use the Metropolis criterion to accept or reject the proposed modifications. However, such stochastic modifications ignore the impact of the choice of targets and their activities on the combination's therapeutic effect and off-target effects, which directly affect the solution quality. In this paper, we present mascot, a method that addresses this limitation by leveraging two additional heuristic criteria to minimize off-target effects and achieve synergy for candidate modification. Specifically, off-target effects measure the unintended response of a signaling network to the target combination and is often associated with toxicity. Synergy occurs when a pair of targets exerts effects that are greater than the sum of their individual effects, and is generally a beneficial strategy for maximizing effect while minimizing toxicity. mascot leverages on a machine learning-based target prioritization method which prioritizes potential targets in a given disease-associated network to select more effective targets (better therapeutic effect and/or lower off-target effects); and on Loewe additivity theory from pharmacology which assesses the non-additive effects in a combination drug treatment to select synergistic target activities. Our experimental study on two disease-related signaling networks demonstrates the superiority of mascot in comparison to existing approaches. Copyright © 2017 Elsevier Inc. All rights reserved.

GPR Signal Denoising and Target Extraction With the CEEMD Method

KAUST Repository

Li, Jing

2015-04-17

In this letter, we apply a time and frequency analysis method based on the complete ensemble empirical mode decomposition (CEEMD) method in ground-penetrating radar (GPR) signal processing. It decomposes the GPR signal into a sum of oscillatory components, with guaranteed positive and smoothly varying instantaneous frequencies. The key idea of this method relies on averaging the modes obtained by empirical mode decomposition (EMD) applied to several realizations of Gaussian white noise added to the original signal. It can solve the mode-mixing problem in the EMD method and improve the resolution of ensemble EMD (EEMD) when the signal has a low signal-to-noise ratio. First, we analyze the difference between the basic theory of EMD, EEMD, and CEEMD. Then, we compare the time and frequency analysis with Hilbert-Huang transform to test the results of different methods. The synthetic and real GPR data demonstrate that CEEMD promises higher spectral-spatial resolution than the other two EMD methods in GPR signal denoising and target extraction. Its decomposition is complete, with a numerically negligible error.

Life prediction of OLED for constant-stress accelerated degradation tests using luminance decaying model

Energy Technology Data Exchange (ETDEWEB)

Zhang, Jianping, E-mail: jpzhanglzu@163.com [College of Energy and Mechanical Engineering, Shanghai University of Electric Power, Shanghai 200090 (China); Li, Wenbin [College of Energy and Mechanical Engineering, Shanghai University of Electric Power, Shanghai 200090 (China); Cheng, Guoliang; Chen, Xiao [Shanghai Tianyi Electric Co., Ltd., Shanghai 201611 (China); Wu, Helen [School of Computing, Engineering and Mathematics, University of Western Sydney, Sydney 2751 (Australia); Herman Shen, M.-H. [Department of Mechanical and Aerospace Engineering, The Ohio State University, OH 43210 (United States)

2014-10-15

In order to acquire the life information of organic light emitting diode (OLED), three groups of constant stress accelerated degradation tests are performed to obtain the luminance decaying data of samples under the condition that the luminance and the current are respectively selected as the indicator of performance degradation and the test stress. Weibull function is applied to describe the relationship between luminance decaying and time, least square method (LSM) is employed to calculate the shape parameter and scale parameter, and the life prediction of OLED is achieved. The numerical results indicate that the accelerated degradation test and the luminance decaying model reveal the luminance decaying law of OLED. The luminance decaying formula fits the test data very well, and the average error of fitting value compared with the test data is small. Furthermore, the accuracy of the OLED life predicted by luminance decaying model is high, which enable rapid estimation of OLED life and provide significant guidelines to help engineers make decisions in design and manufacturing strategy from the aspect of reliability life. - Highlights: • We gain luminance decaying data by accelerated degradation tests on OLED. • The luminance decaying model objectively reveals the decaying law of OLED luminance. • The least square method (LSM) is employed to calculate Weibull parameters. • The plan designed for accelerated degradation tests proves to be feasible. • The accuracy of the OLED life and the luminance decaying fitting formula is high.

Life prediction of OLED for constant-stress accelerated degradation tests using luminance decaying model

International Nuclear Information System (INIS)

Zhang, Jianping; Li, Wenbin; Cheng, Guoliang; Chen, Xiao; Wu, Helen; Herman Shen, M.-H.

2014-01-01

In order to acquire the life information of organic light emitting diode (OLED), three groups of constant stress accelerated degradation tests are performed to obtain the luminance decaying data of samples under the condition that the luminance and the current are respectively selected as the indicator of performance degradation and the test stress. Weibull function is applied to describe the relationship between luminance decaying and time, least square method (LSM) is employed to calculate the shape parameter and scale parameter, and the life prediction of OLED is achieved. The numerical results indicate that the accelerated degradation test and the luminance decaying model reveal the luminance decaying law of OLED. The luminance decaying formula fits the test data very well, and the average error of fitting value compared with the test data is small. Furthermore, the accuracy of the OLED life predicted by luminance decaying model is high, which enable rapid estimation of OLED life and provide significant guidelines to help engineers make decisions in design and manufacturing strategy from the aspect of reliability life. - Highlights: • We gain luminance decaying data by accelerated degradation tests on OLED. • The luminance decaying model objectively reveals the decaying law of OLED luminance. • The least square method (LSM) is employed to calculate Weibull parameters. • The plan designed for accelerated degradation tests proves to be feasible. • The accuracy of the OLED life and the luminance decaying fitting formula is high

Association of proteasomal activity with metastasis in luminal breast cancer

Science.gov (United States)

Shashova, E. E.; Fesik, E. A.; Doroshenko, A. V.

2017-09-01

Chimotrypsin-like (ChTL) and caspase-like (CL) proteasomal activities were investigated in different variants of the tumor progression of luminal breast cancer. Patients with primary luminal breast cancer (n = 123) in stage T1-3N0-2M0 who had not received neoadjuvant treatment were included in this study. Proteasome ChTL and CL activities were determined in the samples of tumor and adjacent tissues. The coefficients of chymotrypsin-like (kChTL) and caspase-like (kCL) proteasome activity were also calculated as the ratio of the corresponding activity in the tumor tissue to activity in the adjacent tissue. ChTL, CL, kChTL and kCL in the tissues of luminal A and B breast cancer with lymphogenic metastasis were compared, and their association with hematogenous metastasis was evaluated. On the one hand, CL activity of proteasomes increased in luminal A breast cancer with extensive lymphogenic metastasis (N2), on the other hand it decreased in the luminal B subtype of cancer. The ratio of proteasomal activity in the tumor and adjacent tissues plays a significant role in the hematogenic pathway of breast cancer progression and is associated with poor metastatic-free survival.

Regulation of HIV-Gag Expression and Targeting to the Endolysosomal/Secretory Pathway by the Luminal Domain of Lysosomal-Associated Membrane Protein (LAMP-1) Enhance Gag-Specific Immune Response

Science.gov (United States)

Lucas, Carolina Gonçalves de Oliveira; Rigato, Paula Ordonhez; Gonçalves, Jorge Luiz Santos; Sato, Maria Notomi; Maciel, Milton; Peçanha, Ligia Maria Torres; August, J. Thomas; de Azevedo Marques, Ernesto Torres; de Arruda, Luciana Barros

2014-01-01

We have previously demonstrated that a DNA vaccine encoding HIV-p55gag in association with the lysosomal associated membrane protein-1 (LAMP-1) elicited a greater Gag-specific immune response, in comparison to a DNA encoding the native gag. In vitro studies have also demonstrated that LAMP/Gag was highly expressed and was present in MHCII containing compartments in transfected cells. In this study, the mechanisms involved in these processes and the relative contributions of the increased expression and altered traffic for the enhanced immune response were addressed. Cells transfected with plasmid DNA constructs containing p55gag attached to truncated sequences of LAMP-1 showed that the increased expression of gag mRNA required p55gag in frame with at least 741 bp of the LAMP-1 luminal domain. LAMP luminal domain also showed to be essential for Gag traffic through lysosomes and, in this case, the whole sequence was required. Further analysis of the trafficking pathway of the intact LAMP/Gag chimera demonstrated that it was secreted, at least in part, associated with exosome-like vesicles. Immunization of mice with LAMP/gag chimeric plasmids demonstrated that high expression level alone can induce a substantial transient antibody response, but targeting of the antigen to the endolysosomal/secretory pathways was required for establishment of cellular and memory response. The intact LAMP/gag construct induced polyfunctional CD4+ T cell response, which presence at the time of immunization was required for CD8+ T cell priming. LAMP-mediated targeting to endolysosomal/secretory pathway is an important new mechanistic element in LAMP-mediated enhanced immunity with applications to the development of novel anti-HIV vaccines and to general vaccinology field. PMID:24932692

NCOA5 is correlated with progression and prognosis in luminal breast cancer

International Nuclear Information System (INIS)

Ye, Xiao-He; Huang, Du-Ping; Luo, Rong-Cheng

2017-01-01

Nuclear receptor coactivator 5 (NCOA5) is known to modulate ERα-mediated transcription and has been found to be involved in the progression of several malignancies. However, the potential correlation between NCOA5 and clinical outcome in patients with luminal breast cancer remains unknown. In the present study, we demonstrated that NCOA5 was significantly up-regulated in luminal breast cancer tissues compared with adjacent non-cancerous tissues both in validated cohort and TCGA cohort. Moreover, Kaplan-Meier analysis indicated that patients with high NOCA5 expression had significantly lower overall survival (P = 0.021). Cox regression analysis indicated that the high NOCA5 expression was independent high risk factor as well as old age (>60) and HER-2 expression (P = 0.039; P = 0.003; P = 0.005; respectively). This study provides new insights and evidences that NOCA5 over-expression was significantly correlated with progression and prognosis in luminal breast cancer. However, the precise cellular mechanisms for NOCA5 in luminal breast cancer need to be further explored. - Highlights: • NCOA5 is significantly over-expressed in human luminal breast cancer tissues. • NOCA5 was involved in the progression of luminal breast cancer. • NCOA5 can predict the progression of luminal breast cancer.

Observations of Ultra-Luminous X-ray Sources, and Implications

Science.gov (United States)

Colbert, E. J. M.

2004-05-01

I will review observations of Ultra-Luminous X-ray Sources (ULXs; Lx > 1E39 erg/s), in particular those observations that have helped reveal the nature of these curious objects. Some recent observations suggest that ULXs are a heterogenous class. Although ULX phenomenology is not fully understood, I will present some examples from the (possibly overlapping) sub-classes. Since ULXs are the most luminous objects in starburst galaxies, they, and ``normal'' luminous black-hole high-mass X-ray binaries are intimately tied to the global galaxian X-ray-star-formation connection. Further work is needed to understand how ULXs form, and how they are associated with the putative population of intermediate-mass black holes.

Cytosolic phospholipase A2-alpha expression in breast cancer is associated with EGFR expression and correlates with an adverse prognosis in luminal tumours.

LENUS (Irish Health Repository)

Caiazza, F

2012-02-01

BACKGROUND: The eicosanoid signalling pathway promotes the progression of malignancies through the production of proliferative prostaglandins (PGs). Cytosolic phospholipase A(2)alpha (cPLA(2)alpha) activity provides the substrate for cyclooxygenase-dependent PG release, and we have previously found that cPLA(2)alpha expression correlated with EGFR\\/HER2 over-expression in a small number of breast cancer cell lines. METHODS: The importance of differential cPLA(2)alpha activity in clinical breast cancer was established by relating the expression of cPLA(2)alpha in tissue samples from breast cancer patients, and two microarray-based gene expression datasets to different clinicopathological and therapeutic parameters. RESULTS: High cPLA(2)alpha mRNA expression correlated with clinical parameters of poor prognosis, which are characteristic of highly invasive tumours of the HER2-positive and basal-like subtype, including low oestrogen receptor expression and high EGFR expression. High cPLA(2)alpha expression decreased overall survival in patients with luminal cancers, and correlated with a reduced effect of tamoxifen treatment. The cPLA(2)alpha expression was an independent predictive parameter of poor response to endocrine therapy in the first 5 years of follow-up. CONCLUSION: This study shows a role of cPLA(2)alpha in luminal breast cancer progression, in which the enzyme could represent a novel therapeutic target and a predictive marker.

Analysis and Simulation of Multi-target Echo Signals from a Phased Array Radar

OpenAIRE

Jia Zhen; Zhou Rui

2017-01-01

The construction of digital radar simulation systems has been a research hotspot of the radar field. This paper focuses on theoretical analysis and simulation of multi-target echo signals produced in a phased array radar system, and constructs an array antenna element and a signal generation environment. The antenna element is able to simulate planar arrays and optimizes these arrays by adding window functions. And the signal environment can model and simulate radar transmission signals, rada...

Chemokine Signaling in Allergic Contact Dermatitis: Toward Targeted Therapies.

Science.gov (United States)

Smith, Jeffrey S; Rajagopal, Sudarshan; Atwater, Amber Reck

2018-06-22

Allergic contact dermatitis (ACD) is a common skin disease that results in significant cost and morbidity. Despite its high prevalence, therapeutic options are limited. Allergic contact dermatitis is regulated primarily by T cells within the adaptive immune system, but also by natural killer and innate lymphoid cells within the innate immune system. The chemokine receptor system, consisting of chemokine peptides and chemokine G protein-coupled receptors, is a critical regulator of inflammatory processes such as ACD. Specific chemokine signaling pathways are selectively up-regulated in ACD, most prominently CXCR3 and its endogenous chemokines CXCL9, CXCL10, and CXCL11. Recent research demonstrates that these 3 chemokines are not redundant and indeed activate distinct intracellular signaling profiles such as those activated by heterotrimeric G proteins and β-arrestin adapter proteins. Such differential signaling provides an attractive therapeutic target for novel ACD therapies and other inflammatory diseases.

The Rac1 hypervariable region in targeting and signaling

Science.gov (United States)

Lam, B. Daniel; Hordijk, Peter L.

2013-01-01

Cellular signaling by small GTPases is critically dependent on proper spatio-temporal orchestration of activation and output. In addition to their core G (guanine nucleotide binding)-domain, small GTPases comprise a hypervariable region (HVR) and a lipid anchor that are generally accepted to control subcellullar localization. The HVR encodes in many small GTPases a polybasic region (PBR) that permits charge-mediated association to the inner leaflet of the plasma membrane or to intracellular organelles. Over the past 15–20 years, evidence has accumulated for specific protein–protein interactions, mediated by the HVR, that control both targeting and signaling specificity of small GTPases. Using the RhoGTPase Rac1 as a paradigm we here review a series of protein partners that require the Rac1 HVR for association and that control various aspects of localized Rac1 signaling. Some of these proteins represent Rac1 activators, whereas others mediate Rac1 inactivation and degradation and yet others potentiate Rac1 downstream signaling. Finally, evidence is discussed which shows that the HVR of Rac1 also contributes to effector interactions, co-operating with the N-terminal effector domain. The complexity of localized Rac1 signaling, reviewed here, is most likely exemplary for many other small GTPases as well, representing a challenge to identify and define similar mechanisms controlling the specific signaling induced by small GTPases. PMID:23354415

HER3 signaling and targeted therapy in cancer

Directory of Open Access Journals (Sweden)

Rosalin Mishra

2018-05-01

Full Text Available ERBB family members including epidermal growth factor receptor (EGFR also known as HER1, ERBB2/HER2/Neu, ERBB3/HER3 and ERBB4/HER4 are aberrantly activated in multiple cancers and hence serve as drug targets and biomarkers in modern precision therapy. The therapeutic potential of HER3 has long been underappreciated, due to impaired kinase activity and relatively low expression in tumors. However, HER3 has received attention in recent years as it is a crucial heterodimeric partner for other EGFR family members and has the potential to regulate EGFR/HER2-mediated resistance. Upregulation of HER3 is associated with several malignancies where it fosters tumor progression via interaction with different receptor tyrosine kinases (RTKs. Studies also implicate HER3 contributing significantly to treatment failure, mostly through the activation of PI3K/AKT, MAPK/ERK and JAK/STAT pathways. Moreover, activating mutations in HER3 have highlighted the role of HER3 as a direct therapeutic target. Therapeutic targeting of HER3 includes abrogating its dimerization partners’ kinase activity using small molecule inhibitors (lapatinib, erlotinib, gefitinib, afatinib, neratinib or direct targeting of its extracellular domain. In this review, we focus on HER3-mediated signaling, its role in drug resistance and discuss the latest advances to overcome resistance by targeting HER3 using mono- and bispecific antibodies and small molecule inhibitors.

Cellular Signaling Pathway Alterations and Potential Targeted Therapies for Medullary Thyroid Carcinoma

Directory of Open Access Journals (Sweden)

Serena Giunti

2013-01-01

Full Text Available Parafollicular C-cell-derived medullary thyroid cancer (MTC comprises 3% to 4% of all thyroid cancers. While cytotoxic treatments have been shown to have limited efficacy, targeted molecular therapies that inhibit rearranged during transfection (RET and other tyrosine kinase receptors that are mainly involved in angiogenesis have shown great promise in the treatment of metastatic or locally advanced MTC. Multi-tyrosine kinase inhibitors such as vandetanib, which is already approved for the treatment of progressive MTC, and cabozantinib have shown distinct advantages with regard to rates of disease response and control. However, these types of tyrosine kinase inhibitor compounds are able to concurrently block several types of targets, which limits the understanding of RET as a specific target. Moreover, important resistances to tyrosine kinase inhibitors can occur, which limit the long-term efficacy of these treatments. Deregulated cellular signaling pathways and genetic alterations in MTC, particularly the activation of the RAS/mammalian target of rapamycin (mTOR cascades and RET crosstalk signaling, are now emerging as novel and potentially promising therapeutic treatments for aggressive MTC.

RANK ligand as a potential target for breast cancer prevention in BRCA1-mutation carriers.

Science.gov (United States)

Nolan, Emma; Vaillant, François; Branstetter, Daniel; Pal, Bhupinder; Giner, Göknur; Whitehead, Lachlan; Lok, Sheau W; Mann, Gregory B; Rohrbach, Kathy; Huang, Li-Ya; Soriano, Rosalia; Smyth, Gordon K; Dougall, William C; Visvader, Jane E; Lindeman, Geoffrey J

2016-08-01

Individuals who have mutations in the breast-cancer-susceptibility gene BRCA1 (hereafter referred to as BRCA1-mutation carriers) frequently undergo prophylactic mastectomy to minimize their risk of breast cancer. The identification of an effective prevention therapy therefore remains a 'holy grail' for the field. Precancerous BRCA1(mut/+) tissue harbors an aberrant population of luminal progenitor cells, and deregulated progesterone signaling has been implicated in BRCA1-associated oncogenesis. Coupled with the findings that tumor necrosis factor superfamily member 11 (TNFSF11; also known as RANKL) is a key paracrine effector of progesterone signaling and that RANKL and its receptor TNFRSF11A (also known as RANK) contribute to mammary tumorigenesis, we investigated a role for this pathway in the pre-neoplastic phase of BRCA1-mutation carriers. We identified two subsets of luminal progenitors (RANK(+) and RANK(-)) in histologically normal tissue of BRCA1-mutation carriers and showed that RANK(+) cells are highly proliferative, have grossly aberrant DNA repair and bear a molecular signature similar to that of basal-like breast cancer. These data suggest that RANK(+) and not RANK(-) progenitors are a key target population in these women. Inhibition of RANKL signaling by treatment with denosumab in three-dimensional breast organoids derived from pre-neoplastic BRCA1(mut/+) tissue attenuated progesterone-induced proliferation. Notably, proliferation was markedly reduced in breast biopsies from BRCA1-mutation carriers who were treated with denosumab. Furthermore, inhibition of RANKL in a Brca1-deficient mouse model substantially curtailed mammary tumorigenesis. Taken together, these findings identify a targetable pathway in a putative cell-of-origin population in BRCA1-mutation carriers and implicate RANKL blockade as a promising strategy in the prevention of breast cancer.

Uterine progesterone signaling is a target for metformin therapy in PCOS-like rats.

Science.gov (United States)

Hu, Min; Zhang, Yuehui; Feng, Jiaxing; Xu, Xue; Zhang, Jiao; Zhao, Wei; Guo, Xiaozhu; Li, Juan; Vestin, Edvin; Cui, Peng; Li, Xin; Wu, Xiao-Ke; Brännström, Mats; Shao, Linus R; Billig, Håkan

2018-05-01

Impaired progesterone (P4) signaling is linked to endometrial dysfunction and infertility in women with polycystic ovary syndrome (PCOS). Here, we report for the first time that elevated expression of progesterone receptor (PGR) isoforms A and B parallels increased estrogen receptor (ER) expression in PCOS-like rat uteri. The aberrant PGR-targeted gene expression in PCOS-like rats before and after implantation overlaps with dysregulated expression of Fkbp52 and Ncoa2 , two genes that contribute to the development of uterine P4 resistance. In vivo and in vitro studies of the effects of metformin on the regulation of the uterine P4 signaling pathway under PCOS conditions showed that metformin directly inhibits the expression of PGR and ER along with the regulation of several genes that are targeted dependently or independently of PGR-mediated uterine implantation. Functionally, metformin treatment corrected the abnormal expression of cell-specific PGR and ER and some PGR-target genes in PCOS-like rats with implantation. Additionally, we documented how metformin contributes to the regulation of the PGR-associated MAPK/ERK/p38 signaling pathway in the PCOS-like rat uterus. Our data provide novel insights into how metformin therapy regulates uterine P4 signaling molecules under PCOS conditions. © 2018 Society for Endocrinology.

Colour polymorphic lures exploit innate preferences for spectral versus luminance cues in dipteran prey.

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White, Thomas E; Kemp, Darrell J

2017-08-14

Theory predicts that colour polymorphism may be favored by variation in the visual context under which signals are perceived. The context encompasses all environmental determinants of light availability and propagation, but also the dynamics of perception in receivers. Color vision involves the neural separation of information into spectral versus luminance channels, which often differentially guide specific tasks. Here we explicitly tested whether this discrete perceptual basis contributes to the maintenance of polymorphism in a prey-luring system. The orb-weaving spider Gasteracantha fornicata is known to attract a broad community of primarily dipteran prey due to their conspicuous banded dorsal signal. They occur in two morphs ("white" and "yellow") which should, respectively, generate greater luminance and color contrast in the dipteran eye. Given that arthropods often rely upon luminance-versus-spectral cues for relatively small-versus-large stimulus detection, we predicted a switch in relative attractiveness among morphs according to apparent spider size. Our experimental tests used colour-naïve individuals of two known prey species (Drosophila hydei and Musca domestica) in replicate Y-maze choice trials designed to manipulate the apparent size of spider models via the distance at which they are viewed. Initial trials confirmed that flies were attracted to each G. fornicata morph in single presentations. When given a simultaneous choice between morphs against a viewing background typical of those encountered in nature, flies exhibited no preference regardless of the visual angle subtended by models. However, when backgrounds were adjusted to nearer the extremes of those of each morph in the wild, flies were more attracted by white morphs when presented at longer range (consistent with a reliance on achromatic cues), yet were unbiased in their close-range choice. While not fully consistent with predictions (given the absence of a differential preference for

Human Mammary Luminal Epithelial Cells Contain Progenitors to Myoepithelial Cells

Energy Technology Data Exchange (ETDEWEB)

Pechoux, Christine; Gudjonsson, Thorarinn; Ronnov-Jessen, Lone; Bissell, Mina J; Petersen, Ole

1999-02-01

The origin of the epithelial and myoepithelial cells in the human breast has not been delineated. In this study we have addressed whether luminal epithelial cells and myoepithelial cells are vertically connected, i.e., whether one is the precursor for the other. We used a primary culture assay allowing preservation of basic phenotypic traits of luminal epithelial and myoepithelial cells in culture. The two cell types were then separated immunomagnetically using antibodies directed against lineage-specific cell surface antigens into at best 100% purity. The cellular identity was ascertained by cytochemistry, immunoblotting, and 2-D gel electrophoresis. Luminal epithelial cells were identified by strong expression of cytokeratins 18 and 19 while myoepithelial cells were recognized by expression of vimentin and {alpha}-smooth muscle actin. We used a previously devised culture medium (CDM4) that allows vigorous expansion of proliferative myoepithelial cells and also devised a medium (CDM6) that allowed sufficient expansion of differentiated luminal epithelial cells based on addition of hepatocyte growth factor/scatter factor. The two different culture media supported each lineage for at least five passages without signs of interconversion. We used parallel cultures where we switched culture media, thus testing the ability of each lineage to convert to the other. Whereas the myoepithelial lineage showed no signs of interconversion, a subset of luminal epithelial cells, gradually, but distinctly, converted to myoepithelial cells. We propose that in the mature human breast, it is the luminal epithelial cell compartment that gives rise to myoepithelial cells rather than the other way around.

Geometry of illumination, luminance contrast, and gloss perception

OpenAIRE

Leloup, Frédéric; Pointer, Michael R.; Dutré, Philip; Hanselaer, Peter

2010-01-01

The influence of both the geometry of illumination and luminance contrast on gloss perception has been examined using the method of paired comparison. Six achromatic glass samples having different lightness were illuminated by two light sources. Only one of these light sources was visible in reflection by the observer. By separate adjustment of the intensity of both light sources, the luminance of both the reflected image and the adjacent off-specular surroundings could be individually varied...

Characteristics of estrogen-induced peroxidase in mouse uterine luminal fluid

International Nuclear Information System (INIS)

Jellinck, P.H.; Newbold, R.R.; McLachlan, J.A.

1991-01-01

Peroxidase activity in the uterine luminal fluid of mice treated with diethylstilbestrol was measured by the guaiacol assay and also by the formation of 3H2O from [2-3H]estradiol. In the radiometric assay, the generation of 3H2O and 3H-labeled water-soluble products was dependent on H2O2 (25 to 100 microM), with higher concentrations being inhibitory. Tyrosine or 2,4-dichlorophenol strongly enhanced the reaction catalyzed either by the luminal fluid peroxidase or the enzyme in the CaCl2 extract of the uterus, but decreased the formation of 3H2O from [2-3H]estradiol by lactoperoxidase in the presence of H2O2 (80 microM). NADPH, ascorbate, and cytochrome c inhibited both luminal fluid and uterine tissue peroxidase activity to the same extent, while superoxide dismutase showed a marginal activating effect. Lactoferrin, a major protein component of uterine luminal fluid, was shown not to contribute to its peroxidative activity, and such an effect by prostaglandin synthase was also ruled out. However, it was not possible to exclude eosinophil peroxidase, brought to the uterus after estrogen stimulation, as being the source of peroxidase activity in uterine luminal fluid

The antidepressant sertraline inhibits translation initiation by curtailing mammalian target of rapamycin signaling.

Science.gov (United States)

Lin, Chen-Ju; Robert, Francis; Sukarieh, Rami; Michnick, Stephen; Pelletier, Jerry

2010-04-15

Sertraline, a selective serotonin reuptake inhibitor, is a widely used antidepressant agent. Here, we show that sertraline also exhibits antiproliferative activity. Exposure to sertraline leads to a concentration-dependent decrease in protein synthesis. Moreover, polysome profile analysis of sertraline-treated cells shows a reduction in polysome content and a concomitant increase in 80S ribosomes. The inhibition in translation caused by sertraline is associated with decreased levels of the eukaryotic initiation factor (eIF) 4F complex, altered localization of eIF4E, and increased eIF2alpha phosphorylation. The latter event leads to increased REDD1 expression, which in turn impinges on the mammalian target of rapamycin (mTOR) pathway by affecting TSC1/2 signaling. Sertraline also independently targets the mTOR signaling pathway downstream of Rheb. In the Emu-myc murine lymphoma model where carcinogenesis is driven by phosphatase and tensin homologue (PTEN) inactivation, sertraline is able to enhance chemosensitivity to doxorubicin. Our results indicate that sertraline exerts antiproliferative activity by targeting the mTOR signaling pathway in a REDD1-dependent manner. (c) 2010 AACR.

A method for evaluating image quality of monochrome and color displays based on luminance by use of a commercially available color digital camera

Energy Technology Data Exchange (ETDEWEB)

Tokurei, Shogo, E-mail: shogo.tokurei@gmail.com, E-mail: junjim@med.kyushu-u.ac.jp [Department of Health Sciences, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, Fukuoka 812-8582, Japan and Department of Radiology, Yamaguchi University Hospital, 1-1-1 Minamikogushi, Ube, Yamaguchi 755-8505 (Japan); Morishita, Junji, E-mail: shogo.tokurei@gmail.com, E-mail: junjim@med.kyushu-u.ac.jp [Department of Health Sciences, Faculty of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, Fukuoka 812-8582 (Japan)

2015-08-15

Purpose: The aim of this study is to propose a method for the quantitative evaluation of image quality of both monochrome and color liquid-crystal displays (LCDs) using a commercially available color digital camera. Methods: The intensities of the unprocessed red (R), green (G), and blue (B) signals of a camera vary depending on the spectral sensitivity of the image sensor used in the camera. For consistent evaluation of image quality for both monochrome and color LCDs, the unprocessed RGB signals of the camera were converted into gray scale signals that corresponded to the luminance of the LCD. Gray scale signals for the monochrome LCD were evaluated by using only the green channel signals of the camera. For the color LCD, the RGB signals of the camera were converted into gray scale signals by employing weighting factors (WFs) for each RGB channel. A line image displayed on the color LCD was simulated on the monochrome LCD by using a software application for subpixel driving in order to verify the WF-based conversion method. Furthermore, the results obtained by different types of commercially available color cameras and a photometric camera were compared to examine the consistency of the authors’ method. Finally, image quality for both the monochrome and color LCDs was assessed by measuring modulation transfer functions (MTFs) and Wiener spectra (WS). Results: The authors’ results demonstrated that the proposed method for calibrating the spectral sensitivity of the camera resulted in a consistent and reliable evaluation of the luminance of monochrome and color LCDs. The MTFs and WS showed different characteristics for the two LCD types owing to difference in the subpixel structure. The MTF in the vertical direction of the color LCD was superior to that of the monochrome LCD, although the WS in the vertical direction of the color LCD was inferior to that of the monochrome LCD as a result of luminance fluctuations in RGB subpixels. Conclusions: The authors�

Study of luminous emissions associated to electron emissions in radiofrequency cavities

International Nuclear Information System (INIS)

Maissa, S.

1996-01-01

This study investigates luminous emissions simultaneously to electron emissions and examines their features in order to better understand the field electron emission phenomenon. A RF cavity, operating at room temperature and in pulsed mode, joined to a sophisticated experimental apparatus has been especially developed. The electron and luminous emissions are investigated on cleaned or with metallic, graphitic and dielectric particles contaminated RF surfaces in order to study their influence on these phenomena. During the surface processing, unstable luminous spots glowing during one RF pulse are detected. Their apparition is promoted in the vicinity of the metallic particles or scratches. Two hypotheses could explain their origin: the presence of micro-plasmas associated to electronic explosive emission during processing or the thermal radiation of the melted metal during this emission. Stable luminous spots glowing during several RF pulses are also detected and appear to increase on RF surfaces contaminated with dielectric particles, leading to strong and explosive luminous emissions. Two interpretations are considered: the initiation of surface breakdowns on the dielectric particles or the heating by the RF field at temperatures sufficiently intense to provoke their thermal radiation then their explosion. Finally a superconducting cavity has been adapted to observe luminous spots, which differ from the former ones bu their star shape and could be associated to micro-plasmas, revealed by the starbursts observed on superconducting cavity walls. (author)

Molecular Pathways for Immune Recognition of Preproinsulin Signal Peptide in Type 1 Diabetes.

Science.gov (United States)

Kronenberg-Versteeg, Deborah; Eichmann, Martin; Russell, Mark A; de Ru, Arnoud; Hehn, Beate; Yusuf, Norkhairin; van Veelen, Peter A; Richardson, Sarah J; Morgan, Noel G; Lemberg, Marius K; Peakman, Mark

2018-04-01

The signal peptide region of preproinsulin (PPI) contains epitopes targeted by HLA-A-restricted (HLA-A0201, A2402) cytotoxic T cells as part of the pathogenesis of β-cell destruction in type 1 diabetes. We extended the discovery of the PPI epitope to disease-associated HLA-B*1801 and HLA-B*3906 (risk) and HLA-A*1101 and HLA-B*3801 (protective) alleles, revealing that four of six alleles present epitopes derived from the signal peptide region. During cotranslational translocation of PPI, its signal peptide is cleaved and retained within the endoplasmic reticulum (ER) membrane, implying it is processed for immune recognition outside of the canonical proteasome-directed pathway. Using in vitro translocation assays with specific inhibitors and gene knockout in PPI-expressing target cells, we show that PPI signal peptide antigen processing requires signal peptide peptidase (SPP). The intramembrane protease SPP generates cytoplasm-proximal epitopes, which are transporter associated with antigen processing (TAP), ER-luminal epitopes, which are TAP independent, each presented by different HLA class I molecules and N-terminal trimmed by ER aminopeptidase 1 for optimal presentation. In vivo, TAP expression is significantly upregulated and correlated with HLA class I hyperexpression in insulin-containing islets of patients with type 1 diabetes. Thus, PPI signal peptide epitopes are processed by SPP and loaded for HLA-guided immune recognition via pathways that are enhanced during disease pathogenesis. © 2018 by the American Diabetes Association.

Measuring high-resolution sky luminance distributions with a CCD camera.

Science.gov (United States)

Tohsing, Korntip; Schrempf, Michael; Riechelmann, Stefan; Schilke, Holger; Seckmeyer, Gunther

2013-03-10

We describe how sky luminance can be derived from a newly developed hemispherical sky imager (HSI) system. The system contains a commercial compact charge coupled device (CCD) camera equipped with a fish-eye lens. The projection of the camera system has been found to be nearly equidistant. The luminance from the high dynamic range images has been calculated and then validated with luminance data measured by a CCD array spectroradiometer. The deviation between both datasets is less than 10% for cloudless and completely overcast skies, and differs by no more than 20% for all sky conditions. The global illuminance derived from the HSI pictures deviates by less than 5% and 20% under cloudless and cloudy skies for solar zenith angles less than 80°, respectively. This system is therefore capable of measuring sky luminance with the high spatial and temporal resolution of more than a million pixels and every 20 s respectively.

Klf5 deletion promotes Pten deletion-initiated luminal-type mouse prostate tumors through multiple oncogenic signaling pathways.

Science.gov (United States)

Xing, Changsheng; Ci, Xinpei; Sun, Xiaodong; Fu, Xiaoying; Zhang, Zhiqian; Dong, Eric N; Hao, Zhao-Zhe; Dong, Jin-Tang

2014-11-01

Krüppel-like factor 5 (KLF5) regulates multiple biologic processes. Its function in tumorigenesis appears contradictory though, showing both tumor suppressor and tumor promoting activities. In this study, we examined whether and how Klf5 functions in prostatic tumorigenesis using mice with prostate-specific deletion of Klf5 and phosphatase and tensin homolog (Pten), both of which are frequently inactivated in human prostate cancer. Histologic analysis demonstrated that when one Pten allele was deleted, which causes mouse prostatic intraepithelial neoplasia (mPIN), Klf5 deletion accelerated the emergence and progression of mPIN. When both Pten alleles were deleted, which causes prostate cancer, Klf5 deletion promoted tumor growth, increased cell proliferation, and caused more severe morphologic and molecular alterations. Homozygous deletion of Klf5 was more effective than hemizygous deletion. Unexpectedly, while Pten deletion alone expanded basal cell population in a tumor as reported, Klf5 deletion in the Pten-null background clearly reduced basal cell population while expanding luminal cell population. Global gene expression profiling, pathway analysis, and experimental validation indicate that multiple mechanisms could mediate the tumor-promoting effect of Klf5 deletion, including the up-regulation of epidermal growth factor and its downstream signaling molecules AKT and ERK and the inactivation of the p15 cell cycle inhibitor. KLF5 also appears to cooperate with several transcription factors, including CREB1, Sp1, Myc, ER and AR, to regulate gene expression. These findings validate the tumor suppressor function of KLF5. They also yield a mouse model that shares two common genetic alterations with human prostate cancer-mutation/deletion of Pten and deletion of Klf5.

Luminance compensation for AMOLED displays using integrated MIS sensors

Science.gov (United States)

Vygranenko, Yuri; Fernandes, Miguel; Louro, Paula; Vieira, Manuela

2017-05-01

Active-matrix organic light-emitting diodes (AMOLEDs) are ideal for future TV applications due to their ability to faithfully reproduce real images. However, pixel luminance can be affected by instability of driver TFTs and aging effect in OLEDs. This paper reports on a pixel driver utilizing a metal-insulator-semiconductor (MIS) sensor for luminance control of the OLED element. In the proposed pixel architecture for bottom-emission AMOLEDs, the embedded MIS sensor shares the same layer stack with back-channel etched a Si:H TFTs to maintain the fabrication simplicity. The pixel design for a large-area HD display is presented. The external electronics performs image processing to modify incoming video using correction parameters for each pixel in the backplane, and also sensor data processing to update the correction parameters. The luminance adjusting algorithm is based on realistic models for pixel circuit elements to predict the relation between the programming voltage and OLED luminance. SPICE modeling of the sensing part of the backplane is performed to demonstrate its feasibility. Details on the pixel circuit functionality including the sensing and programming operations are also discussed.

Luminous flux and colour maintenance investigation of integrated LED lamps

DEFF Research Database (Denmark)

Corell, Dennis Dan; Thorseth, Anders; Dam-Hansen, Carsten

2014-01-01

This article will present an investigation of the luminous flux and colour maintenance of white LED based retrofit lamps. The study includes 23 different types of integrated LED lamps, covering 18 directional and 5 non-directional. Luminous flux and colour data for operation up to 20000 h has been...

An evaluation of organic light emitting diode monitors for medical applications: great timing, but luminance artifacts.

Science.gov (United States)

Elze, Tobias; Taylor, Christopher; Bex, Peter J

2013-09-01

In contrast to the dominant medical liquid crystal display (LCD) technology, organic light-emitting diode (OLED) monitors control the display luminance via separate light-emitting diodes for each pixel and are therefore supposed to overcome many previously documented temporal artifacts of medical LCDs. We assessed the temporal and luminance characteristics of the only currently available OLED monitor designed for use in the medical treatment field (SONY PVM2551MD) and checked the authors' main findings with another SONY OLED device (PVM2541). Temporal properties of the photometric output were measured with an optical transient recorder. Luminances of the three color primaries and white for all 256 digital driving levels (DDLs) were measured with a spectroradiometer. Between the luminances of neighboring DDLs, just noticeable differences were calculated according to a perceptual model developed for medical displays. Luminances of full screen (FS) stimuli were compared to luminances of smaller stimuli with identical DDLs. All measured luminance transition times were below 300 μs. Luminances were independent of the luminance in the preceding frame. However, for the single color primaries, up to 50.5% of the luminances of neighboring DDLs were not perceptually distinguishable. If two color primaries were active simultaneously, between 36.7% and 55.1% of neighboring luminances for increasing DDLs of the third primary were even decreasing. Moreover, luminance saturation effects were observed when too many pixels were active simultaneously. This effect was strongest for white; a small white patch was close to 400 cd/m(2), but in FS the luminance of white saturated at 162 cd/m(2). Due to different saturation levels, the luminance of FS green and FS yellow could exceed the luminance of FS white for identical DDLs. The OLED temporal characteristics are excellent and superior to those of LCDs. However, the OLEDs revealed severe perceptually relevant artifacts with

Monte Carlo Simulation of the Echo Signals from Low-Flying Targets for Airborne Radar

Directory of Open Access Journals (Sweden)

Mingyuan Man

2014-01-01

Full Text Available A demonstrated hybrid method based on the combination of half-space physical optics method (PO, graphical-electromagnetic computing (GRECO, and Monte Carlo method on echo signals from low-flying targets based on actual environment for airborne radar is presented in this paper. The half-space physical optics method , combined with the graphical-electromagnetic computing (GRECO method to eliminate the shadow regions quickly and rebuild the target automatically, is employed to calculate the radar cross section (RCS of the conductive targets in half space fast and accurately. The direct echo is computed based on the radar equation. The reflected paths from sea or ground surface cause multipath effects. In order to accurately obtain the echo signals, the phase factors are modified for fluctuations in multipath, and the statistical average value of the echo signals is obtained using the Monte Carlo method. A typical simulation is performed, and the numerical results show the accuracy of the proposed method.

Targeting GPCR-Gβγ-GRK2 signaling as a novel strategy for treating cardiorenal pathologies.

Science.gov (United States)

Rudomanova, Valeria; Blaxall, Burns C

2017-08-01

The pathologic crosstalk between the heart and kidney is known as cardiorenal syndrome (CRS). While the specific mechanisms underlying this crosstalk remain poorly understood, CRS is associated with exacerbated dysfunction of either or both organs and reduced survival. Maladaptive fibrotic remodeling is a key component of both heart and kidney failure pathogenesis and progression. G-protein coupled receptor (GPCR) signaling is a crucial regulator of cardiovascular and renal function. Chronic/pathologic GPCR signaling elicits the interaction of the G-protein Gβγ subunit with GPCR kinase 2 (GRK2), targeting the receptor for internalization, scaffolding to pathologic signals, and receptor degradation. Targeting this pathologic Gβγ-GRK2 interaction has been suggested as a possible strategy for the treatment of HF. In the current review, we discuss recent updates in understanding the role of GPCR-Gβγ-GRK2 signaling as a crucial mediator of maladaptive organ remodeling detected in HF and kidney dysfunction, with specific attention to small molecule-mediated inhibition of pathologic Gβγ-GRK2 interactions. Further, we explore the potential of GPCR-Gβγ-GRK2 signaling as a possible therapeutic target for cardiorenal pathologies. Copyright © 2017 Elsevier B.V. All rights reserved.

Effects of luminal flow and nucleotides on [Ca(2+)](i) in rabbit cortical collecting duct.

Science.gov (United States)

Woda, Craig B; Leite, Maurilo; Rohatgi, Rajeev; Satlin, Lisa M

2002-09-01

Nucleotide binding to purinergic P2 receptors contributes to the regulation of a variety of physiological functions in renal epithelial cells. Whereas P2 receptors have been functionally identified at the basolateral membrane of the cortical collecting duct (CCD), a final regulatory site of urinary Na(+), K(+), and acid-base excretion, controversy exists as to whether apical purinoceptors exist in this segment. Nor has the distribution of receptor subtypes present on the unique cell populations that constitute Ca(2+) the CCD been established. To examine this, we measured nucleotide-induced changes in intracellular Ca(2+) concentration ([Ca(2+)](i)) in fura 2-loaded rabbit CCDs microperfused in vitro. Resting [Ca(2+)](i) did not differ between principal and intercalated cells, averaging approximately 120 nM. An acute increase in tubular fluid flow rate, associated with a 20% increase in tubular diameter, led to increases in [Ca(2+)](i) in both cell types. Luminal perfusion of 100 microM UTP or ATP-gamma-S, in the absence of change in flow rate, caused a rapid and transient approximately fourfold increase in [Ca(2+)](i) in both cell types (P < 0.05). Luminal suramin, a nonspecific P2 receptor antagonist, blocked the nucleotide- but not flow-induced [Ca(2+)](i) transients. Luminal perfusion with a P2X (alpha,beta-methylene-ATP), P2X(7) (benzoyl-benzoyl-ATP), P2Y(1) (2-methylthio-ATP), or P2Y(4)/P2Y(6) (UDP) receptor agonist had no effect on [Ca(2+)](i). The nucleotide-induced [Ca(2+)](i) transients were inhibited by the inositol-1,4,5-triphosphate receptor blocker 2-aminoethoxydiphenyl borate, thapsigargin, which depletes internal Ca(2+) stores, luminal perfusion with a Ca(2+)-free perfusate, or the L-type Ca(2+) channel blocker nifedipine. These results suggest that luminal nucleotides activate apical P2Y(2) receptors in the CCD via pathways that require both internal Ca(2+) mobilization and extracellular Ca(2+) entry. The flow-induced rise in [Ca(2+)](i) is

Covariation of Color and Luminance Facilitate Object Individuation in Infancy

Science.gov (United States)

Woods, Rebecca J.; Wilcox, Teresa

2010-01-01

The ability to individuate objects is one of our most fundamental cognitive capacities. Recent research has revealed that when objects vary in color or luminance alone, infants fail to individuate those objects until 11.5 months. However, color and luminance frequently covary in the natural environment, thus providing a more salient and reliable…

Optimal Solution Volume for Luminal Preservation: A Preclinical Study in Porcine Intestinal Preservation.

Science.gov (United States)

Oltean, M; Papurica, M; Jiga, L; Hoinoiu, B; Glameanu, C; Bresler, A; Patrut, G; Grigorie, R; Ionac, M; Hellström, M

2016-03-01

Rodent studies suggest that luminal solutions alleviate the mucosal injury and prolong intestinal preservation but concerns exist that excessive volumes of luminal fluid may promote tissue edema. Differences in size, structure, and metabolism between rats and humans require studies in large animals before clinical use. Intestinal procurement was performed in 7 pigs. After perfusion with histidine-tryptophan-ketoglutarate (HTK), 40-cm-long segments were cut and filled with 13.5% polyethylene glycol (PEG) 3350 solution as follows: V0 (controls, none), V1 (0.5 mL/cm), V2 (1 mL/cm), V3 (1.5 mL/cm), and V4 (2 mL/cm). Tissue and luminal solutions were sampled after 8, 14, and 24 hours of cold storage (CS). Preservation injury (Chiu score), the apical membrane (ZO-1, brush-border maltase activity), and the electrolyte content in the luminal solution were studied. In control intestines, 8-hour CS in HTK solution resulted in minimal mucosal changes (grade 1) that progressed to significant subepithelial edema (grade 3) by 24 hours. During this time, a gradual loss in ZO-1 was recorded, whereas maltase activity remained unaltered. Moreover, variable degrees of submucosal edema were observed. Luminal introduction of high volumes (2 mL/mL) of PEG solution accelerated the development of the subepithelial edema and submucosal edema, leading to worse histology. However, ZO-1 was preserved better over time than in control intestines (no luminal solution). Maltase activity was reduced in intestines receiving luminal preservation. Luminal sodium content decreased in time and did not differ between groups. This PEG solution protects the apical membrane and the tight-junction proteins but may favor water absorption and tissue (submucosal) edema, and luminal volumes >2 mL/cm may result in worse intestinal morphology. Copyright © 2016 Elsevier Inc. All rights reserved.

High-mobility group box 1 released by autophagic cancer-associated fibroblasts maintains the stemness of luminal breast cancer cells.

Science.gov (United States)

Zhao, Xi-Long; Lin, Yong; Jiang, Jun; Tang, Zhuo; Yang, Shuai; Lu, Lu; Liang, Yan; Liu, Xue; Tan, Jiao; Hu, Xu-Gang; Niu, Qin; Fu, Wen-Juan; Yan, Ze-Xuan; Guo, De-Yu; Ping, Yi-Fang; Wang, Ji Ming; Zhang, Xia; Kung, Hsiang-Fu; Bian, Xiu-Wu; Yao, Xiao-Hong

2017-11-01

Cancer stem cells/cancer-initiating cells (CICs) and their microenvironmental niche play a vital role in malignant tumour recurrence and metastasis. Cancer-associated fibroblasts (CAFs) are major components of the niche of breast cancer-initiating cells (BCICs), and their interactions may profoundly affect breast cancer progression. Autophagy has been considered to be a critical process for CIC maintenance, but whether it is involved in the cross-talk between CAFs and CICs to affect tumourigenesis and pathological significance has not been determined. In this study, we found that the presence of CAFs containing high levels of microtubule-associated protein 1 light chain 3 (LC3II), a marker of autophagosomes, was associated with more aggressive luminal human breast cancer. CAFs in human luminal breast cancer tissues with high autophagy activity enriched BCICs with increased tumourigenicity. Mechanistically, autophagic CAFs released high-mobility group box 1 (HMGB1), which activated its receptor, Toll-like receptor (TLR) 4, expressed by luminal breast cancer cells, to enhance their stemness and tumourigenicity. Furthermore, immunohistochemistry of 180 luminal breast cancers revealed that high LC3II/TLR4 levels predicted an increased relapse rate and a poorer prognosis. Our findings demonstrate that autophagic CAFs play a critical role in promoting the progression of luminal breast cancer through an HMGB1-TLR4 axis, and that both autophagy in CAFs and TLR4 on breast cancer cells constitute potential therapeutic targets. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Asymmetric effects of luminance and chrominance in the watercolor illusion

Directory of Open Access Journals (Sweden)

Andrew eCoia

2014-09-01

Full Text Available When bounded by a line of sufficient contrast, the desaturated hue of a colored line will spread over an enclosed area, an effect known as the watercolor illusion. The contrast of the two lines can be in luminance, chromaticity, or a combination of both. The effect is most salient when the enclosing line has greater contrast with the background than the line that induces the spreading color. In most prior experiments with watercolor spreading, the luminance of both lines has been lower than the background. An achromatic version of the illusion exists where a dark line will spread while being bounded by either a darker or brighter line. In a previous study we measured the strength of the watercolor effect in which the colored inducing line was isoluminant to the background, and found an illusion for both brighter and darker achromatic outer contours. We also found the strength of spreading is stronger for bluish (+S cone input colors compared to yellowish (-S cone input ones, when bounded by a dark line. The current study set out to measure the hue dependence of the watercolor illusion when inducing colors are flanked with brighter (increment as opposed to darker outer lines. The asymmetry in the watercolor effect with S cone input was enhanced when the inducing contrast was an increment rather than a decrement. Further experiments explored the relationship between the perceived contrast of these chromatic lines when paired with luminance increments and decrements and revealed that the perceived contrast of luminance increments and decrements is dependent on which isoluminant color they are paired with. In addition to known hue asymmetries in the watercolor illusion there are asymmetries between luminance increments and decrements that are also hue dependent. These latter asymmetries may be related to the perceived contrast of the hue/luminance parings.

Asymmetric effects of luminance and chrominance in the watercolor illusion.

Science.gov (United States)

Coia, Andrew J; Crognale, Michael A

2014-01-01

When bounded by a line of sufficient contrast, the desaturated hue of a colored line will spread over an enclosed area, an effect known as the watercolor illusion. The contrast of the two lines can be in luminance, chromaticity, or a combination of both. The effect is most salient when the enclosing line has greater contrast with the background than the line that induces the spreading color. In most prior experiments with watercolor spreading, the luminance of both lines has been lower than the background. An achromatic version of the illusion exists where a dark line will spread while being bounded by either a darker or brighter line. In a previous study we measured the strength of the watercolor effect in which the colored inducing line was isoluminant to the background, and found an illusion for both brighter and darker achromatic outer contours. We also found the strength of spreading is stronger for bluish (+S cone input) colors compared to yellowish (-S cone input) ones, when bounded by a dark line. The current study set out to measure the hue dependence of the watercolor illusion when inducing colors are flanked with brighter (increment) as opposed to darker outer lines. The asymmetry in the watercolor effect with S cone input was enhanced when the inducing contrast was an increment rather than a decrement. Further experiments explored the relationship between the perceived contrast of these chromatic lines when paired with luminance increments and decrements and revealed that the perceived contrast of luminance increments and decrements is dependent on which isoluminant color they are paired with. In addition to known hue asymmetries in the watercolor illusion there are asymmetries between luminance increments and decrements that are also hue dependent. These latter asymmetries may be related to the perceived contrast of the hue/luminance parings.

An experimental study regarding diagnostic accuracy on image interpretation of the digital image film by using viewboxes of different luminance

International Nuclear Information System (INIS)

Song Shaojuan; Huang Ling; Liu Chuanya; Zhang Xiaojing

2009-01-01

Objective: To evaluate diagnostic accuracy of image interpretation using viewboxes at different luminance with ALVIM statistical phantom (TRG). Methods: A digital film of TRG image was obtained by exposing the phantom of TRG with Kodak DR 3000 using proper parameter. Viewboxes with three different luminance were selected from those used in daily work. The film of TRG was evaluated with these viewboxes of three different luminance by three different radiologists with experience of five, eight and sixteen years respectively. A grade scale of 5 was used to evaluate each row of signal and noise. According to the results and formula, the probabilities of true-positive [P(S/s)], false-positive [P(S/n)] and true answer (P det ) were obtained. Results: The three kinds of luminance used in viewboxes were: (3489± 256), (2231±220), (816±168) cd/m 2 . When the average luminance of viewbox was 3489 cd/m 2 , P det of 0.6,0.7,0.8 mm in bone substitute was 0.558±0.009, 0.788±0.008, 0.813±0.006, P det of 0.9, 1.0, 1.2 mm in muscle substitute was 0.663±0.010, 0.750±0.008, 0.933±0.005; When the average luminance of viewbox was 2231 cd/m 2 , P det of 0.6,0.7,0.8 mm in bone substitute was 0.525±0.013, 0.713±0.013,0.775±0.016, P det of 0.9,1.0,1.2 mm in muscle substitute was 0.613±0.019, 0.650± 0.013,0.850±0.019; When the average luminance of viewbox was 816 cd/m 2 , Pact of 0.6,0.7,0.8 mm in bone substitute was 0.475±0.022,0.550±0.018,0.688±0.020, P det of 0.9, 1.0, 1.2 mm in muscle substitute was 0.550±0.025,0.575±0.021,0.725±0.016. Viewboxes of different luminance were compared to one another by paired t-test. The results of comparison all had significant statistical differences (t=5.057 and 4.681, P<0.05). Conclusions: The image displayed by viewboxes at different luminance had significant influence on image interpretation. The higher the luminace of viewbox, the richer the information displayed, and the higher the accuracy of diagnosis. (authors)

Target of Rapamycin (TOR) Regulates Growth in Response to Nutritional Signals.

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Weisman, Ronit

2016-10-01

All organisms can respond to the availability of nutrients by regulating their metabolism, growth, and cell division. Central to the regulation of growth in response to nutrient availability is the target of rapamycin (TOR) signaling that is composed of two structurally distinct complexes: TOR complex 1 (TORC1) and TOR complex 2 (TORC2). The TOR genes were first identified in yeast as target of rapamycin, a natural product of a soil bacterium, which proved beneficial as an immunosuppressive and anticancer drug and is currently being tested for a handful of other pathological conditions including diabetes, neurodegeneration, and age-related diseases. Studies of the TOR pathway unraveled a complex growth-regulating network. TOR regulates nutrient uptake, transcription, protein synthesis and degradation, as well as metabolic pathways, in a coordinated manner that ensures that cells grow or cease growth in response to nutrient availability. The identification of specific signals and mechanisms that stimulate TOR signaling is an active and exciting field of research that has already identified nitrogen and amino acids as key regulators of TORC1 activity. The signals, as well as the cellular functions of TORC2, are far less well understood. Additional open questions in the field concern the relationships between TORC1 and TORC2, as well as the links with other nutrient-responsive pathways. Here I review the main features of TORC1 and TORC2, with a particular focus on yeasts as model organisms.

A pocket-sized luminance meter.

NARCIS (Netherlands)

Schreuder, D.A.

1964-01-01

In many case the light technician will feel the want of assessing the luminance of certain surfaces within his field of view in a quick and convenient manner. The measurement need not be very accurate, but it should be carried out with an apparatus so small that it can easily be taken along

Effects of the Maximum Luminance in a Medical-grade Liquid-crystal Display on the Recognition Time of a Test Pattern: Observer Performance Using Landolt Rings.

Science.gov (United States)

Doi, Yasuhiro; Matsuyama, Michinobu; Ikeda, Ryuji; Hashida, Masahiro

2016-07-01

This study was conducted to measure the recognition time of the test pattern and to investigate the effects of the maximum luminance in a medical-grade liquid-crystal display (LCD) on the recognition time. Landolt rings as signals of the test pattern were used with four random orientations, one on each of the eight gray-scale steps. Ten observers input the orientation of the gap on the Landolt rings using cursor keys on the keyboard. The recognition times were automatically measured from the display of the test pattern on the medical-grade LCD to the input of the orientation of the gap in the Landolt rings. The maximum luminance in this study was set to one of four values (100, 170, 250, and 400 cd/m(2)), for which the corresponding recognition times were measured. As a result, the average recognition times for each observer with maximum luminances of 100, 170, 250, and 400 cd/m(2) were found to be 3.96 to 7.12 s, 3.72 to 6.35 s, 3.53 to 5.97 s, and 3.37 to 5.98 s, respectively. The results indicate that the observer's recognition time is directly proportional to the luminance of the medical-grade LCD. Therefore, it is evident that the maximum luminance of the medical-grade LCD affects the test pattern recognition time.

MicroRNA-145 suppresses hepatocellular carcinoma by targeting IRS1 and its downstream Akt signaling

Energy Technology Data Exchange (ETDEWEB)

Wang, Yelin [Department of Anesthesiology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou (China); Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou (China); Hu, Chen; Cheng, Jun [Department of Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou (China); Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou (China); Chen, Binquan [Department of Anesthesiology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou (China); Ke, Qinghong; Lv, Zhen; Wu, Jian [Department of Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou (China); Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou (China); Zhou, Yanfeng, E-mail: zyfhdj@yahoo.com [Department of Anesthesiology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou (China)

2014-04-18

Highlights: • MiR-145 expression is down-regulated in HCC tissues and inversely related with IRS1 levels. • MiR-145 directly targets IRS1 in HCC cells. • Restored expression of miR-145 suppressed HCC cell proliferation and growth. • MiR-145 induced IRS1 under-expression potentially reduced downstream AKT signaling. - Abstract: Accumulating evidences have proved that dysregulation of microRNAs (miRNAs) is involved in cancer initiation and progression. In this study, we showed that miRNA-145 level was significantly decreased in hepatocellular cancer (HCC) tissues and cell lines, and its low expression was inversely associated with the abundance of insulin receptor substrate 1 (IRS1), a key mediator in oncogenic insulin-like growth factor (IGF) signaling. We verified IRS1 as a direct target of miR-145 using Western blotting and luciferase reporter assay. Further, the restoration of miR-145 in HCC cell lines suppressed cancer cell growth, owing to down-regulated IRS1 expression and its downstream Akt/FOXO1 signaling. Our results demonstrated that miR-145 could inhibit HCC through targeting IRS1 and its downstream signaling, implicating the loss of miR-145 regulation may be a potential molecular mechanism causing aberrant oncogenic signaling in HCC.

White LEDs with limit luminous efficacy

Energy Technology Data Exchange (ETDEWEB)

Lisitsyn, V. M.; Stepanov, S. A., E-mail: stepanovsa@tpu.ru; Yangyang, Ju [National Research Tomsk Polytechnic University, 30 Lenin Av., Tomsk, 634050 (Russian Federation); Lukash, V. S. [JSC Research Institute of Semiconductor Devices, 99a Krasnoarmeyskaja St., Tomsk, 634050 (Russian Federation)

2016-01-15

In most promising widespread gallium nitride based LEDs emission is generated in the blue spectral region with a maximum at about 450 nm which is converted to visible light with the desired spectrum by means of phosphor. The thermal energy in the conversion is determined by the difference in the energies of excitation and emission quanta and the phosphor quantum yield. Heat losses manifest themselves as decrease in the luminous efficacy. LED heating significantly reduces its efficiency and life. In addition, while heating, the emission generation output and the efficiency of the emission conversion decrease. Therefore, the reduction of the energy losses caused by heating is crucial for LED development. In this paper, heat losses in phosphor-converted LEDs (hereinafter chips) during spectrum conversion are estimated. The limit values of the luminous efficacy for white LEDs are evaluated.

Identification of potential pathway mediation targets in Toll-like receptor signaling.

Directory of Open Access Journals (Sweden)

Fan Li

2009-02-01

Full Text Available Recent advances in reconstruction and analytical methods for signaling networks have spurred the development of large-scale models that incorporate fully functional and biologically relevant features. An extended reconstruction of the human Toll-like receptor signaling network is presented herein. This reconstruction contains an extensive complement of kinases, phosphatases, and other associated proteins that mediate the signaling cascade along with a delineation of their associated chemical reactions. A computational framework based on the methods of large-scale convex analysis was developed and applied to this network to characterize input-output relationships. The input-output relationships enabled significant modularization of the network into ten pathways. The analysis identified potential candidates for inhibitory mediation of TLR signaling with respect to their specificity and potency. Subsequently, we were able to identify eight novel inhibition targets through constraint-based modeling methods. The results of this study are expected to yield meaningful avenues for further research in the task of mediating the Toll-like receptor signaling network and its effects.

Overlapping activities of TGF-β and Hedgehog signaling in cancer: therapeutic targets for cancer treatment.

Science.gov (United States)

Perrot, Carole Y; Javelaud, Delphine; Mauviel, Alain

2013-02-01

Recent advances in the field of cancer therapeutics come from the development of drugs that specifically recognize validated oncogenic or pro-metastatic targets. The latter may be mutated proteins with altered function, such as kinases that become constitutively active, or critical components of growth factor signaling pathways, whose deregulation leads to aberrant malignant cell proliferation and dissemination to metastatic sites. We herein focus on the description of the overlapping activities of two important developmental pathways often exacerbated in cancer, namely Transforming Growth Factor-β (TGF-β) and Hedgehog (HH) signaling, with a special emphasis on the unifying oncogenic role played by GLI1/2 transcription factors. The latter are the main effectors of the canonical HH pathway, yet are direct target genes of TGF-β/SMAD signal transduction. While tumor-suppressor in healthy and pre-malignant tissues, TGF-β is often expressed at high levels in tumors and contributes to tumor growth, escape from immune surveillance, invasion and metastasis. HH signaling regulates cell proliferation, differentiation and apoptosis, and aberrant HH signaling is found in a variety of cancers. We discuss the current knowledge on HH and TGF-β implication in cancer including cancer stem cell biology, as well as the current state, both successes and failures, of targeted therapeutics aimed at blocking either of these pathways in the pre-clinical and clinical settings. Copyright © 2012 Elsevier Inc. All rights reserved.

Leptin signaling molecular actions and drug target in hepatocellular carcinoma

Directory of Open Access Journals (Sweden)

Jiang N

2014-11-01

Full Text Available Nan Jiang,1,* Rongtong Sun,2,* Qing Sun3 1Shandong University School of Medicine, Jinan, Shandong Province, People’s Republic of China; 2Weihai Municipal Hospital, Weihai, Shandong Province, People’s Republic of China; 3Department of Pathology, QianFoShan Hospital Affiliated to Shandong University, Jinan, Shandong Province, People’s Republic of China *These authors contributed equally to this work Abstract: Previous reports indicate that over 13 different tumors, including hepatocellular carcinoma (HCC, are related to obesity. Obesity-associated inflammatory, metabolic, and endocrine mediators, as well as the functioning of the gut microbiota, are suspected to contribute to tumorigenesis. In obese people, proinflammatory cytokines/chemokines including tumor necrosis factor-alpha, interleukin (IL-1 and IL-6, insulin and insulin-like growth factors, adipokines, plasminogen activator inhibitor-1, adiponectin, and leptin are found to play crucial roles in the initiation and development of cancer. The cytokines induced by leptin in adipose tissue or tumor cells have been intensely studied. Leptin-induced signaling pathways are critical for biological functions such as adiposity, energy balance, endocrine function, immune reaction, and angiogenesis as well as oncogenesis. Leptin is an activator of cell proliferation and anti-apoptosis in several cell types, and an inducer of cancer stem cells; its critical roles in tumorigenesis are based on its oncogenic, mitogenic, proinflammatory, and pro-angiogenic actions. This review provides an update of the pathological effects of leptin signaling with special emphasis on potential molecular mechanisms and therapeutic targeting, which could potentially be used in future clinical settings. In addition, leptin-induced angiogenic ability and molecular mechanisms in HCC are discussed. The stringent binding affinity of leptin and its receptor Ob-R, as well as the highly upregulated expression of both

Realization of an optical multi and mono-channel analyzer, associated to a streak camera. Application to metrology of picosecond low intensity luminous pulses

International Nuclear Information System (INIS)

Roth, J.M.

1985-02-01

An electronic system including a low light level television tube (Nocticon) to digitize images from streak cameras is studied and realized. Performances (sensibility, signal-to-noise ratio) are studied and compared with a multi-channel analyzer using a linear network of photodiodes. It is applied to duration and amplitude measurement of short luminous pulses [fr

Labor Inhibits Placental Mechanistic Target of Rapamycin Complex 1 Signaling

Science.gov (United States)

LAGER, Susanne; AYE, Irving L.M.H.; GACCIOLI, Francesca; RAMIREZ, Vanessa I.; JANSSON, Thomas; POWELL, Theresa L.

2014-01-01

Introduction Labor induces a myriad of changes in placental gene expression. These changes may represent a physiological adaptation inhibiting placental cellular processes associated with a high demand for oxygen and energy (e.g., protein synthesis and active transport) thereby promoting oxygen and glucose transfer to the fetus. We hypothesized that mechanistic target of rapamycin complex 1 (mTORC1) signaling, a positive regulator of trophoblast protein synthesis and amino acid transport, is inhibited by labor. Methods Placental tissue was collected from healthy, term pregnancies (n=15 no-labor; n=12 labor). Activation of Caspase-1, IRS1/Akt, STAT, mTOR, and inflammatory signaling pathways was determined by Western blot. NFκB p65 and PPARγ DNA binding activity was measured in isolated nuclei. Results Labor increased Caspase-1 activation and mTOR complex 2 signaling, as measured by phosphorylation of Akt (S473). However, mTORC1 signaling was inhibited in response to labor as evidenced by decreased phosphorylation of mTOR (S2448) and 4EBP1 (T37/46 and T70). Labor also decreased NFκB and PPARγ DNA binding activity, while having no effect on IRS1 or STAT signaling pathway. Discussion and conclusion Several placental signaling pathways are affected by labor, which has implications for experimental design in studies of placental signaling. Inhibition of placental mTORC1 signaling in response to labor may serve to down-regulate protein synthesis and amino acid transport, processes that account for a large share of placental oxygen and glucose consumption. We speculate that this response preserves glucose and oxygen for transfer to the fetus during the stressful events of labor. PMID:25454472

MicroRNA-200, associated with metastatic breast cancer, promotes traits of mammary luminal progenitor cells.

Science.gov (United States)

Sánchez-Cid, Lourdes; Pons, Mònica; Lozano, Juan José; Rubio, Nuria; Guerra-Rebollo, Marta; Soriano, Aroa; Paris-Coderch, Laia; Segura, Miquel F; Fueyo, Raquel; Arguimbau, Judit; Zodda, Erika; Bermudo, Raquel; Alonso, Immaculada; Caparrós, Xavier; Cascante, Marta; Rafii, Arash; Kang, Yibin; Martínez-Balbás, Marian; Weiss, Stephen J; Blanco, Jerónimo; Muñoz, Montserrat; Fernández, Pedro L; Thomson, Timothy M

2017-10-13

MicroRNAs are critical regulators of gene networks in normal and abnormal biological processes. Focusing on invasive ductal breast cancer (IDC), we have found dysregulated expression in tumor samples of several microRNAs, including the miR-200 family, along progression from primary tumors to distant metastases, further reflected in higher blood levels of miR-200b and miR-7 in IDC patients with regional or distant metastases relative to patients with primary node-negative tumors. Forced expression of miR-200s in MCF10CA1h mammary cells induced an enhanced epithelial program, aldehyde dehydrogenase (ALDH) activity, mammosphere growth and ability to form branched tubuloalveolar structures while promoting orthotopic tumor growth and lung colonization in vivo . MiR-200s also induced the constitutive activation of the PI3K-Akt signaling through downregulation of PTEN, and the enhanced mammosphere growth and ALDH activity induced in MCF10CA1h cells by miR-200s required the activation of this signaling pathway. Interestingly, the morphology of tumors formed in vivo by cells expressing miR-200s was reminiscent of metaplastic breast cancer (MBC). Indeed, the epithelial components of MBC samples expressed significantly higher levels of miR-200s than their mesenchymal components and displayed a marker profile compatible with luminal progenitor cells. We propose that microRNAs of the miR-200 family promote traits of highly proliferative breast luminal progenitor cells, thereby exacerbating the growth and metastatic properties of transformed mammary epithelial cells.

MicroRNA-99 family targets AKT/mTOR signaling pathway in dermal wound healing.

Science.gov (United States)

Jin, Yi; Tymen, Stéphanie D; Chen, Dan; Fang, Zong Juan; Zhao, Yan; Dragas, Dragan; Dai, Yang; Marucha, Phillip T; Zhou, Xiaofeng

2013-01-01

Recent studies suggest that microRNAs play important roles in dermal wound healing and microRNA deregulation has been linked with impaired wound repair. Here, using a mouse experimental wound healing model, we identified a panel of 63 differentially expressed microRNAs during dermal wound healing, including members of miR-99 family (miR-99a, miR-99b, miR-100). We further demonstrated that miR-99 family members regulate cell proliferation, cell migration, and AKT/mTOR signaling. Combined experimental and bioinformatics analyses revealed that miR-99 family members regulate AKT/mTOR signaling by targeting multiple genes, including known target genes (e.g., IGF1R, mTOR) and a new target (AKT1). The effects of miR-99 family members on the expression of IGF1R, mTOR and AKT1 were validated at both the mRNA and protein levels. Two adjacent miR-99 family targeting sites were identified in the 3'-UTR of the AKT1 mRNA. The direct interaction of miR-100 with these targeting sites was confirmed using luciferase reporter assays. The microRNA-100-directed recruitment of AKT1 mRNA to the RNAi-induced silencing complex (RISC) was confirmed by a ribonucleoprotein-IP assay. In summary, we identified a panel of differentially expressed microRNAs which may play important roles in wound healing. We provide evidence that miR-99 family members contribute to wound healing by regulating the AKT/mTOR signaling.

Effect of Ionizing Radiation on Luminous Bacteria Cells

International Nuclear Information System (INIS)

Kudryasheva, N.; Rozhko, T.; Alexandrova, M.; Vasyunkina, E.; Arkhipova, V.

2011-01-01

Marine luminous bacteria were used to monitor toxicity of alpha- (Am-241, U-235+238) and beta- (tritium) radionuclide solutions. Increase or inhibition of bacterial luminescence was observed under exposure to radionuclides. Radiation toxicity of Am and chemical toxicity of U were demonstrated. Effects of U were similar to those of stable heavy metals: sensitivity was about 10-5 M. Sensitivity of the bacteria to Am-241 was 300 Bq/L (10 -11 M). Inhibition of bacterial growth was observed under exposure to Am-241 and tritium. Role of peroxides and electron transfer processes in the effects of radionuclides on luminous bacteria is discussed.

Signal integration: a framework for understanding the efficacy of therapeutics targeting the human EGFR family

Science.gov (United States)

Shepard, H. Michael; Brdlik, Cathleen M.; Schreiber, Hans

2008-01-01

The human EGFR (HER) family is essential for communication between many epithelial cancer cell types and the tumor microenvironment. Therapeutics targeting the HER family have demonstrated clinical success in the treatment of diverse epithelial cancers. Here we propose that the success of HER family–targeted monoclonal antibodies in cancer results from their ability to interfere with HER family consolidation of signals initiated by a multitude of other receptor systems. Ligand/receptor systems that initiate these signals include cytokine receptors, chemokine receptors, TLRs, GPCRs, and integrins. We further extrapolate that improvements in cancer therapeutics targeting the HER family are likely to incorporate mechanisms that block or reverse stromal support of malignant progression by isolating the HER family from autocrine and stromal influences. PMID:18982164

Relationship of the luminous bacterial symbiont of the Caribbean flashlight fish, Kryptophanaron alfredi (family Anomalopidae) to other luminous bacteria based on bacterial luciferase (luxA) genes.

Science.gov (United States)

Haygood, M G

1990-01-01

Flashlight fishes (family Anomalopidae) have light organs that contain luminous bacterial symbionts. Although the symbionts have not yet been successfully cultured, the luciferase genes have been cloned directly from the light organ of the Caribbean species, Kryptophanaron alfredi. The goal of this project was to evaluate the relationship of the symbiont to free-living luminous bacteria by comparison of genes coding for bacterial luciferase (lux genes). Hybridization of a lux AB probe from the Kryptophanaron alfredi symbiont to DNAs from 9 strains (8 species) of luminous bacteria showed that none of the strains tested had lux genes highly similar to the symbiont. The most similar were a group consisting of Vibrio harveyi, Vibrio splendidus and Vibrio orientalis. The nucleotide sequence of the luciferase alpha subunit gene luxA) of the Kryptophanaron alfredi symbiont was determined in order to do a more detailed comparison with published luxA sequences from Vibrio harveyi, Vibrio fischeri and Photobacterium leiognathi. The hybridization results, sequence comparisons and the mol% G + C of the Kryptophanaron alfredi symbiont luxA gene suggest that the symbiont may be considered as a new species of luminous Vibrio related to Vibrio harveyi.

Densities, cellulases, alginate and pectin lyases of luminous and other heterotrophic bacteria associated with marine algae

Digital Repository Service at National Institute of Oceanography (India)

Ramaiah, N.; Chandramohan, D.

Epiphytic luminous and non-luminous bacteria were determined quantitatively for eight intertidal algal species from rocky beaches of Goa and Lakshadweep coral reef lagoon. Luminous bacteria were present on all eight algal species and contributed 2...

Comparison of luminance based metrics in different lighting conditions

DEFF Research Database (Denmark)

Wienold, J.; Kuhn, T.E.; Christoffersen, J.

In this study, we evaluate established and newly developed metrics for predicting glare using data from three different research studies. The evaluation covers two different targets: 1. How well the user’s perception of glare magnitude correlates to the prediction of the glare metrics? 2. How well...... do the glare metrics describe the subjects’ disturbance by glare? We applied Spearman correlations, logistic regressions and an accuracy evaluation, based on an ROC-analysis. The results show that five of the twelve investigated metrics are failing at least one of the statistical tests. The other...... seven metrics CGI, modified DGI, DGP, Ev, average Luminance of the image Lavg, UGP and UGR are passing all statistical tests. DGP, CGI, DGI_mod and UGP have largest AUC and might be slightly more robust. The accuracy of the predictions of afore mentioned seven metrics for the disturbance by glare lies...

Reproducibility of airway luminal size in asthma measured by HRCT.

Science.gov (United States)

Brown, Robert H; Henderson, Robert J; Sugar, Elizabeth A; Holbrook, Janet T; Wise, Robert A

2017-10-01

Brown RH, Henderson RJ, Sugar EA, Holbrook JT, Wise RA, on behalf of the American Lung Association Airways Clinical Research Centers. Reproducibility of airway luminal size in asthma measured by HRCT. J Appl Physiol 123: 876-883, 2017. First published July 13, 2017; doi:10.1152/japplphysiol.00307.2017.-High-resolution CT (HRCT) is a well-established imaging technology used to measure lung and airway morphology in vivo. However, there is a surprising lack of studies examining HRCT reproducibility. The CPAP Trial was a multicenter, randomized, three-parallel-arm, sham-controlled 12-wk clinical trial to assess the use of a nocturnal continuous positive airway pressure (CPAP) device on airway reactivity to methacholine. The lack of a treatment effect of CPAP on clinical or HRCT measures provided an opportunity for the current analysis. We assessed the reproducibility of HRCT imaging over 12 wk. Intraclass correlation coefficients (ICCs) were calculated for individual airway segments, individual lung lobes, both lungs, and air trapping. The ICC [95% confidence interval (CI)] for airway luminal size at total lung capacity ranged from 0.95 (0.91, 0.97) to 0.47 (0.27, 0.69). The ICC (95% CI) for airway luminal size at functional residual capacity ranged from 0.91 (0.85, 0.95) to 0.32 (0.11, 0.65). The ICC measurements for airway distensibility index and wall thickness were lower, ranging from poor (0.08) to moderate (0.63) agreement. The ICC for air trapping at functional residual capacity was 0.89 (0.81, 0.94) and varied only modestly by lobe from 0.76 (0.61, 0.87) to 0.95 (0.92, 0.97). In stable well-controlled asthmatic subjects, it is possible to reproducibly image unstimulated airway luminal areas over time, by region, and by size at total lung capacity throughout the lungs. Therefore, any changes in luminal size on repeat CT imaging are more likely due to changes in disease state and less likely due to normal variability. NEW & NOTEWORTHY There is a surprising lack

Luminal Cells Are Favored as the Cell of Origin for Prostate Cancer

Directory of Open Access Journals (Sweden)

Zhu A. Wang

2014-09-01

Full Text Available The identification of cell types of origin for cancer has important implications for tumor stratification and personalized treatment. For prostate cancer, the cell of origin has been intensively studied, but it has remained unclear whether basal or luminal epithelial cells, or both, represent cells of origin under physiological conditions in vivo. Here, we use a novel lineage-tracing strategy to assess the cell of origin in a diverse range of mouse models, including Nkx3.1+/−; Pten+/−, Pten+/−, Hi-Myc, and TRAMP mice, as well as a hormonal carcinogenesis model. Our results show that luminal cells are consistently the observed cell of origin for each model in situ; however, explanted basal cells from these mice can generate tumors in grafts. Consequently, we propose that luminal cells are favored as cells of origin in many contexts, whereas basal cells only give rise to tumors after differentiation into luminal cells.

Targeting Sonic Hedgehog Signaling by Compounds and Derivatives from Natural Products

Directory of Open Access Journals (Sweden)

Yu-Chuen Huang

2013-01-01

Full Text Available Cancer stem cells (CSCs are a major cause of cancer treatment failure, relapse, and drug resistance and are known to be responsible for cancer cell invasion and metastasis. The Sonic hedgehog (Shh signaling pathway is crucial to embryonic development. Intriguingly, the aberrant activation of the Shh pathway plays critical roles in developing CSCs and leads to angiogenesis, migration, invasion, and metastasis. Natural compounds and chemical structure modified derivatives from complementary and alternative medicine have received increasing attention as cancer chemopreventives, and their antitumor effects have been demonstrated both in vitro and in vivo. However, reports for their bioactivity against CSCs and specifically targeting Shh signaling remain limited. In this review, we summarize investigations of the compounds cyclopamine, curcumin, epigallocatechin-3-gallate, genistein, resveratrol, zerumbone, norcantharidin, and arsenic trioxide, with a focus on Shh signaling blockade. Given that Shh signaling antagonism has been clinically proven as effective strategy against CSCs, this review may be exploitable for development of novel anticancer agents from complementary and alternative medicine.

The time course of color- and luminance-based salience effects.

Directory of Open Access Journals (Sweden)

Isabel C Dombrowe

2010-11-01

Full Text Available Salient objects in the visual field attract our attention. Recent work in the orientation domain has shown that the effects of the relative salience of two singleton elements on covert visual attention disappear over time. The present study aims to investigate how salience derived from color and luminance differences affects covert selection. In two experiments, observers indicated the location of a probe which was presented at different stimulus-onset-asynchronies after the presentation of a singleton display containing a homogeneous array of oriented lines and two distinct color singletons (Experiment 1 or luminance singletons (Experiment 2. The results show that relative singleton salience from luminance and color differences, just as from orientation differences, affects covert visual attention in a brief time span after stimulus onset. The mere presence of an object, however, can affect covert attention for a longer time span regardless of salience.

Non-genomic actions of aldosterone: From receptors and signals to membrane targets.

LENUS (Irish Health Repository)

2012-02-01

In tissues which express the mineralocorticoid receptor (MR), aldosterone modulates the expression of membrane targets such as the subunits of the epithelial Na(+) channel, in combination with important signalling intermediates such as serum and glucocorticoid-regulated kinase-1. In addition, the rapid \\'non-genomic\\' activation of protein kinases and secondary messenger signalling cascades has also been detected in aldosterone-sensitive tissues of the nephron, distal colon and cardiovascular system. These rapid actions are variously described as being coupled to MR or to an as yet unidentified, membrane-associated aldosterone receptor. The rapidly activated signalling cascades add a level of fine-tuning to the activity of aldosterone-responsive membrane transporters and also modulate the aldosterone-induced changes in gene expression through receptor and transcription factor phosphorylation.

Non-genomic actions of aldosterone: From receptors and signals to membrane targets.

LENUS (Irish Health Repository)

Dooley, Ruth

2011-07-26

In tissues which express the mineralocorticoid receptor (MR), aldosterone modulates the expression of membrane targets such as the subunits of the epithelial Na(+) channel, in combination with important signalling intermediates such as serum and glucocorticoid-regulated kinase-1. In addition, the rapid \\'non-genomic\\' activation of protein kinases and secondary messenger signalling cascades has also been detected in aldosterone-sensitive tissues of the nephron, distal colon and cardiovascular system. These rapid actions are variously described as being coupled to MR or to an as yet unidentified, membrane-associated aldosterone receptor. The rapidly activated signalling cascades add a level of fine-tuning to the activity of aldosterone-responsive membrane transporters and also modulate the aldosterone-induced changes in gene expression through receptor and transcription factor phosphorylation.

The impact of luminance on tonic and phasic pupillary responses to sustained cognitive load.

Science.gov (United States)

Peysakhovich, Vsevolod; Vachon, François; Dehais, Frédéric

2017-02-01

Pupillary reactions independent of light conditions have been linked to cognition for a long time. However, the light conditions can impact the cognitive pupillary reaction. Previous studies underlined the impact of luminance on pupillary reaction, but it is still unclear how luminance modulates the sustained and transient components of pupillary reaction - tonic pupil diameter and phasic pupil response. In the present study, we investigated the impact of the luminance on these two components under sustained cognitive load. Fourteen participants performed a novel working memory task combining mathematical computations with a classic n-back task. We studied both tonic pupil diameter and phasic pupil response under low (1-back) and high (2-back) working memory load and two luminance levels (gray and white). We found that the impact of working memory load on the tonic pupil diameter was modulated by the level of luminance, the increase in tonic pupil diameter with the load being larger under lower luminance. In contrast, the smaller phasic pupil response found under high load remained unaffected by luminance. These results showed that luminance impacts the cognitive pupillary reaction - tonic pupil diameter (phasic pupil response) being modulated under sustained (respectively, transient) cognitive load. These findings also support the relationship between the locus-coeruleus system, presumably functioning in two firing modes - tonic and phasic - and the pupil diameter. We suggest that the tonic pupil diameter tracks the tonic activity of the locus-coeruleus while phasic pupil response reflects its phasic activity. Besides, the designed novel cognitive paradigm allows the simultaneous manipulation of sustained and transient components of the cognitive load and is useful for dissociating the effects on the tonic pupil diameter and phasic pupil response. Copyright © 2016 Elsevier B.V. All rights reserved.

Effects of background and contour luminance on the hue and brightness of the Watercolor effect.

Science.gov (United States)

Gerardin, Peggy; Dojat, Michel; Knoblauch, Kenneth; Devinck, Frédéric

2018-03-01

Conjoint measurement was used to investigate the joint influences of the luminance of the background and the inner contour on hue- and brightness filling-in for a stimulus configuration generating a water-color effect (WCE), i.e., a wiggly bi-chromatic contour enclosing a region with the lower luminance component on the exterior. Two stimuli with the background and inner contour luminances covarying independently were successively presented, and in separate experiments, the observer judged which member of the pair's interior regions contained a stronger hue or was brighter. Braided-contour control stimuli that generated little or no perceptual filling-in were also used to assess whether observers were judging the interior regions and not the contours themselves. Three nested models of the contributions of the background and inner contour to the judgments were fit to the data by maximum likelihood and evaluated by likelihood ratio tests. Both stimulus components contributed to both the hue and brightness of the interior region with increasing luminance of the inner contour generating an assimilative filling-in for the hue judgments but a contrast effect for the brightness judgments. Control analyses showed negligible effects for the order of the luminance of the background or inner contour on the judgments. An additive contribution of both components was rejected in favor of a saturated model in which the responses depended on the levels of both stimulus components. For the hue judgments, increased background luminance led to greater hue filling-in at higher luminances of the interior contour. For the brightness judgments, the higher background luminance generated less brightness filling-in at higher luminances of the interior contour. The results indicate different effects of the inner contour and background on the induction of the brightness and coloration percepts of the WCE, suggesting that they are mediated by different mechanisms. Copyright © 2018 Elsevier

Effect of microbubble ligation to cells on ultrasound signal enhancement: implications for targeted imaging.

Science.gov (United States)

Lankford, Miles; Behm, Carolyn Z; Yeh, James; Klibanov, Alexander L; Robinson, Peter; Lindner, Jonathan R

2006-10-01

Molecular imaging with contrast-enhanced ultrasound (CEU) relies on the detection of microbubbles retained in regions of disease. The aim of this study was to determine whether microbubble attachment to cells influences their acoustic signal generation and stability. Biotinylated microbubbles were attached to streptavidin-coated plates to derive density versus intensity relations during low- and high-power imaging. To assess damping from microbubble attachment to solid or cell surfaces, in vitro imaging was performed for microbubbles charge-coupled to methacrylate spheres and for vascular cell adhesion molecule-1-targeted microbubbles attached to endothelial cells. Signal enhancement on plates increased according to acoustic power and microbubble site density up to 300 mm. Microbubble signal was reduced by attachment to solid spheres during high- and low-power imaging but was minimally reduced by attachment to endothelial cells and only at low power. Attachment of targeted microbubbles to rigid surfaces results in damping and a reduction of their acoustic signal, which is not seen when microbubbles are attached to cells. A reliable concentration versus intensity relationship can be expected from microbubble attachment to 2-dimensional surfaces until a very high site density is reached.

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

DEFF Research Database (Denmark)

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

2008-01-01

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

Near-field visual acuity of pigeons: effects of head location and stimulus luminance.

Science.gov (United States)

Hodos, W; Leibowitz, R W; Bonbright, J C

1976-03-01

Two pigeons were trained to discriminate a grating stimulus from a blank stimulus of equivalent luminance in a three-key chamber. The stimuli and blanks were presented behind a transparent center key. The procedure was a conditional discrimination in which pecks on the left key were reinforced if the blank had been present behind the center key and pecks on the right key were reinforced if the grating had been present behind the center key. The spatial frequency of the stimuli was varied in each session from four to 29.5 lines per millimeter in accordance with a variation of the method of constant stimuli. The number of lines per millimeter that the subjects could discriminate at threshold was determined from psychometric functions. Data were collected at five values of stimulus luminance ranging from--0.07 to 3.29 log cd/m2. The distance from the stimulus to the anterior nodal point of the eye, which was determined from measurements taken from high-speed motion-picture photographs of three additional pigeons and published intraocular measurements, was 62.0 mm. This distance and the grating detection thresholds were used to calculate the visual acuity of the birds at each level of luminance. Acuity improved with increasing luminance to a peak value of 0.52, which corresponds to a visual angle of 1.92 min, at a luminance of 2.33 log cd/m2. Further increase in luminance produced a small decline in acuity.

Mercury-free electrodeless discharge lamp: effect of xenon pressure and plasma parameters on luminance

International Nuclear Information System (INIS)

Nazri Dagang Ahmad; Kondo, Akira; Motomura, Hideki; Jinno, Masafumi

2009-01-01

Since there is much concern about environmental preservation, the authors have paid attention to the uses of mercury in lighting application. They have focused on the application of the xenon low-pressure inductively coupled plasma (ICP) discharge in developing cylindrical type mercury-free light sources. ICP can be operated at low filling gas pressures and demonstrates significant potential in producing high density plasma. Xenon pressure was varied from 0.1 to 100 Torr and the lamp luminance was measured. The gas pressure dependence shows an increase in luminance at pressures below 1 Torr. In order to clarify this behaviour, measurement of plasma parameters was carried out using the double probe method and its relation to lamp luminance is discussed. As the gas pressure is decreased (from 1 to 0.01 Torr), the electron temperature increases while the electron density decreases while at the same time the lamp luminance increases. There are several factors that are believed to contribute to the increase in luminance in the very low pressure region. Increases in luminance are considered to be due to the electron-ion recombination process which brings a strong recombination radiation in continuum in the visible region and also due to the effect of stochastic heating.

Luminance gradient at object borders communicates object location to the human oculomotor system.

Science.gov (United States)

Kilpeläinen, Markku; Georgeson, Mark A

2018-01-25

The locations of objects in our environment constitute arguably the most important piece of information our visual system must convey to facilitate successful visually guided behaviour. However, the relevant objects are usually not point-like and do not have one unique location attribute. Relatively little is known about how the visual system represents the location of such large objects as visual processing is, both on neural and perceptual level, highly edge dominated. In this study, human observers made saccades to the centres of luminance defined squares (width 4 deg), which appeared at random locations (8 deg eccentricity). The phase structure of the square was manipulated such that the points of maximum luminance gradient at the square's edges shifted from trial to trial. The average saccade endpoints of all subjects followed those shifts in remarkable quantitative agreement. Further experiments showed that the shifts were caused by the edge manipulations, not by changes in luminance structure near the centre of the square or outside the square. We conclude that the human visual system programs saccades to large luminance defined square objects based on edge locations derived from the points of maximum luminance gradients at the square's edges.

Paul Callaghan luminous moments

CERN Document Server

Callaghan, Paul

2013-01-01

Acknowledged internationally for his ground-breaking scientific research in the field of magnetic resonance, Sir Paul Callaghan was a scientist and visionary with a rare gift for promoting science to a wide audience. He was named New Zealander of the Year in 2011. His death in early 2012 robbed New Zealand of an inspirational leader. Paul Callaghan: Luminous Moments brings together some of his most significant writing. Whether he describes his childhood in Wanganui, reflects on discovering the beauty of science, sets out New Zealand's future potential or discusses the experience of fa

Lithium inhibits tumorigenic potential of PDA cells through targeting hedgehog-GLI signaling pathway.

Directory of Open Access Journals (Sweden)

Zhonglu Peng

Full Text Available Hedgehog signaling pathway plays a critical role in the initiation and development of pancreatic ductal adenocarcinoma (PDA and represents an attractive target for PDA treatment. Lithium, a clinical mood stabilizer for mental disorders, potently inhibits the activity of glycogen synthase kinase 3β (GSK3β that promotes the ubiquitin-dependent proteasome degradation of GLI1, an important downstream component of hedgehog signaling. Herein, we report that lithium inhibits cell proliferation, blocks G1/S cell-cycle progression, induces cell apoptosis and suppresses tumorigenic potential of PDA cells through down-regulation of the expression and activity of GLI1. Moreover, lithium synergistically enhances the anti-cancer effect of gemcitabine. These findings further our knowledge of mechanisms of action for lithium and provide a potentially new therapeutic strategy for PDA through targeting GLI1.

Targeting CB2-GPR55 Receptor Heteromers Modulates Cancer Cell Signaling*

Science.gov (United States)

Moreno, Estefanía; Andradas, Clara; Medrano, Mireia; Caffarel, María M.; Pérez-Gómez, Eduardo; Blasco-Benito, Sandra; Gómez-Cañas, María; Pazos, M. Ruth; Irving, Andrew J.; Lluís, Carme; Canela, Enric I.; Fernández-Ruiz, Javier; Guzmán, Manuel; McCormick, Peter J.; Sánchez, Cristina

2014-01-01

The G protein-coupled receptors CB2 (CB2R) and GPR55 are overexpressed in cancer cells and human tumors. Because a modulation of GPR55 activity by cannabinoids has been suggested, we analyzed whether this receptor participates in cannabinoid effects on cancer cells. Here we show that CB2R and GPR55 form heteromers in cancer cells, that these structures possess unique signaling properties, and that modulation of these heteromers can modify the antitumoral activity of cannabinoids in vivo. These findings unveil the existence of previously unknown signaling platforms that help explain the complex behavior of cannabinoids and may constitute new targets for therapeutic intervention in oncology. PMID:24942731

Relationships between luminance and visual acuity in the rhesus monkey

Science.gov (United States)

Cavonius, C. R.; Robbins, D. O.

1973-01-01

1. The ability of rhesus monkeys to detect the gap in Landolt ring test-objects that were presented against background luminances between 5 × 10-5 cd/m2 and 5 × 103 cd/m2 was compared with similar human data. 2. At high luminance-levels the acuity of human observers is slightly better than that of rhesus, but rhesus have better acuity at scotopic luminance-levels. Both species have distinct photopic and scotopic acuity functions that cross at 6 × 10-3 cd/m2. 3. The threshold for light detection is estimated to be the same for both species when specified in quanta incident on the retina. 4. It is concluded that the receptor and neural mechanisms that mediate visual-acuity function similarly in rhesus and man, and that the differences in acuity that were measured in the two species may be attributed to optical rather than to physiological factors. PMID:4199366

Luminal progenitors restrict their lineage potential during mammary gland development.

Science.gov (United States)

Rodilla, Veronica; Dasti, Alessandro; Huyghe, Mathilde; Lafkas, Daniel; Laurent, Cécile; Reyal, Fabien; Fre, Silvia

2015-02-01

The hierarchical relationships between stem cells and progenitors that guide mammary gland morphogenesis are still poorly defined. While multipotent basal stem cells have been found within the myoepithelial compartment, the in vivo lineage potential of luminal progenitors is unclear. Here we used the expression of the Notch1 receptor, previously implicated in mammary gland development and tumorigenesis, to elucidate the hierarchical organization of mammary stem/progenitor cells by lineage tracing. We found that Notch1 expression identifies multipotent stem cells in the embryonic mammary bud, which progressively restrict their lineage potential during mammary ductal morphogenesis to exclusively generate an ERαneg luminal lineage postnatally. Importantly, our results show that Notch1-labelled cells represent the alveolar progenitors that expand during pregnancy and survive multiple successive involutions. This study reveals that postnatal luminal epithelial cells derive from distinct self-sustained lineages that may represent the cells of origin of different breast cancer subtypes.

MicroRNA-467g inhibits new bone regeneration by targeting Ihh/Runx-2 signaling.

Science.gov (United States)

Kureel, Jyoti; John, Aijaz A; Dixit, Manisha; Singh, Divya

2017-04-01

MicroRNAs are important post transcriptional regulators of gene expression and play critical role in osteoblast differentiation. In this study we report miR-467g, an uncharacterized novel miRNA, in regulation of osteoblast functions. Over-expression of miR-467g inhibited osteoblast differentiation. Target prediction analysis tools and experimental validation by luciferase 3' UTR reporter assay identified Runx-2 as a direct target of miR-467g. Over expression of miR-467g in osteoblasts down regulated Runx-2 and Ihh signaling components. Furthermore, silencing of miR-467g was done to see its role in Ihh and Runx-2 mediated bone healing and regeneration in a drill hole injury model in BALB/c mice. Silencing of miR-467g led to significant increase in new bone regeneration and Ihh and Runx-2 localization at injury site in a day dependent manner. In conclusion, miR-467g negatively regulates osteogenesis by targeting Ihh/Runx-2 signaling. We, thus, propose that therapeutic approaches targeting miR-467g could be useful in enhancing the new bone formation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Geometry of illumination, luminance contrast, and gloss perception.

Science.gov (United States)

Leloup, Frédéric B; Pointer, Michael R; Dutré, Philip; Hanselaer, Peter

2010-09-01

The influence of both the geometry of illumination and luminance contrast on gloss perception has been examined using the method of paired comparison. Six achromatic glass samples having different lightness were illuminated by two light sources. Only one of these light sources was visible in reflection by the observer. By separate adjustment of the intensity of both light sources, the luminance of both the reflected image and the adjacent off-specular surroundings could be individually varied. It was found that visual gloss appraisal did not correlate with instrumentally measured specular gloss; however, psychometric contrast seemed to be a much better correlate. It has become clear that not only the sample surface characteristics determine gloss perception: the illumination geometry could be an even more important factor.

Luminance-based specular gloss characterization

OpenAIRE

Leloup, Frédéric; Pointer, Michael R.; Dutré, Philip; Hanselaer, Peter

2011-01-01

Gloss is a feature of visual appearance that arises from the directionally selective reflection of light incident on a surface. Especially when a distinct reflected image is perceptible, the luminance distribution of the illumination scene above the sample can strongly influence the gloss perception. For this reason, industrial glossmeters do not provide a satisfactory gloss estimation of high-gloss surfaces. In this study, the influence of the conditions of illumination on specular ...

Notch3 marks clonogenic mammary luminal progenitor cells in vivo.

Science.gov (United States)

Lafkas, Daniel; Rodilla, Veronica; Huyghe, Mathilde; Mourao, Larissa; Kiaris, Hippokratis; Fre, Silvia

2013-10-14

The identity of mammary stem and progenitor cells remains poorly understood, mainly as a result of the lack of robust markers. The Notch signaling pathway has been implicated in mammary gland development as well as in tumorigenesis in this tissue. Elevated expression of the Notch3 receptor has been correlated to the highly aggressive "triple negative" human breast cancer. However, the specific cells expressing this Notch paralogue in the mammary gland remain unknown. Using a conditionally inducible Notch3-CreERT2(SAT) transgenic mouse, we genetically marked Notch3-expressing cells throughout mammary gland development and followed their lineage in vivo. We demonstrate that Notch3 is expressed in a highly clonogenic and transiently quiescent luminal progenitor population that gives rise to a ductal lineage. These cells are capable of surviving multiple successive pregnancies, suggesting a capacity to self-renew. Our results also uncover a role for the Notch3 receptor in restricting the proliferation and consequent clonal expansion of these cells.

Dimensionally Specific Capture of Attention: Implications for Saliency Computation

Directory of Open Access Journals (Sweden)

Katherine E. Burnett

2018-02-01

Full Text Available Observers automatically orient to a sudden change in the environment. This is demonstrated experimentally using exogenous cues, which prioritize the analysis of subsequent targets appearing nearby. This effect has been attributed to the computation of saliency, obtained by combining features specific signals, which then feed back to drive attention to the salient location. An alternative possibility is that cueing directly effects target-evoked sensory responses in a feed-forward manner. We examined the effects of luminance and equiluminant color cues in a dual task paradigm, which required both a motion and a color discrimination. Equiluminant color cues improved color discrimination more than luminance cues, but luminance cues improved motion discrimination more than equiluminant color cues. This suggests that the effects of exogenous cues are dimensionally specific and may not depend entirely on the computation of a dimension general saliency signal.

MGAT1 is a novel transcriptional target of Wnt/β-catenin signaling pathway.

Science.gov (United States)

Akiva, Izzet; Birgül Iyison, Necla

2018-01-08

The Wnt/β-catenin signaling pathway is an evolutionary conserved pathway, which has important functions in vertebrate early development, axis formation, cellular proliferation and morphogenesis. Additionally, Wnt/β-catenin signaling pathway is one of the most important intracellular pathways that controls cancer progression. To date most of the identified targets of this pathway are shown to harbor tumorigenic properties. We previously showed that Mannosyl glycoprotein acetylglucosaminyl-transferase (MGAT1) enzyme is among the Wnt/β-catenin signaling putative target genes in hepatocellular carcinoma cell lines (Huh7). MGAT1 protein levels were determined by Western Blotting from Huh7 cell lines in which Wnt/β-catenin pathway was activated by means of different approaches such as LiCl treatment and mutant β-catenin overexpression. Luciferase reporter assay was used to analyze the promoter activity of MGAT1. The mRNA levels of MGAT1 were determined by quantitative real-time PCR from Huh7 cells that were treated with either Wnt agonist or GSK-3β inhibitor. Wound healing and XTT cell proliferation assays were performed in order to determine the proliferation and migration capacities of MGAT1 overexpressing stable Huh7 cells. Finally, xenograft experiments were carried out to measure the tumor formation capacities in vivo. In this study we showed that the activation of Wnt/β-catenin pathway culminates in the upregulation of MGAT1 enzyme both at transcriptional and post-transcriptional levels. We also showed that overexpression of the β-catenin gene (CTNNB1) increased the promoter activity of MGAT1. We applied a set of complementary approaches to elucidate the functional importance of MGAT1 as a vital target of Wnt/β-catenin signaling in Huh7 cells. Our analyses related to cell proliferation and migration assays showed that in comparison to the control cells, MGAT1 expressing Huh7 cells have greater proliferative and invasive capabilities. Furthermore, the

Cloning and characterization of luciferase from a Fijian luminous click beetle.

Science.gov (United States)

Mitani, Yasuo; Futahashi, Ryo; Niwa, Kazuki; Ohba, Nobuyoshi; Ohmiya, Yoshihiro

2013-01-01

Luminous click beetle is distributed almost exclusively in Central and South America with a single genus in Melanesia. Among these click beetles, the description of Melanesian species has been fragmentary, and its luciferase gene and phylogenetic relation to other click beetles still remain uncertain. We collected a living luminous click beetle, Photophorus jansonii in Fiji. It emits green-yellow light from two spots on the pronotum and has no ventral luminous organ. Here, we cloned a luciferase gene from this insect by RT-PCR. The deduced amino acid sequence showed high identity of ~85% to the luciferases derived from other click beetle species. The luciferase of the Fijian click beetle was produced as a recombinant protein to characterize its biochemical properties. The Km for D-luciferin and ATP were 173 and 270 μm, respectively. The luciferase was pH-insensitive and the spectrum measured at pH 8.0 showed a peak at 559 nm, which was in the range of green-yellow light as seen in the luminous spot of the living Fijian click beetle. The Fijian click beetle luciferase was assigned to the Elateridae clade by a phylogenetic analysis, but it made a clearly different branch from Pyrophorus group examined in this study. © 2013 The American Society of Photobiology.

Signal recovery in imaging photoplethysmography

International Nuclear Information System (INIS)

Holton, Benjamin D; Mannapperuma, Kavan; Lesniewski, Peter J; Thomas, John C

2013-01-01

Imaging photoplethysmography is an emerging technique for the extraction of biometric information from people using video recordings. The focus is on extracting the cardiac heart rate of the subject by analysing the luminance of the colour video signal and identifying periodic components. Advanced signal processing is needed to recover the information required. In this paper, independent component analysis (ICA), principal component analysis, auto- and cross-correlation are investigated and compared with respect to their effectiveness in extracting the relevant information from video recordings. Results obtained are compared with those recorded by a modern commercial finger pulse oximeter. It is found that ICA produces the most consistent results. (paper)

Signal recovery in imaging photoplethysmography.

Science.gov (United States)

Holton, Benjamin D; Mannapperuma, Kavan; Lesniewski, Peter J; Thomas, John C

2013-11-01

Imaging photoplethysmography is an emerging technique for the extraction of biometric information from people using video recordings. The focus is on extracting the cardiac heart rate of the subject by analysing the luminance of the colour video signal and identifying periodic components. Advanced signal processing is needed to recover the information required. In this paper, independent component analysis (ICA), principal component analysis, auto- and cross-correlation are investigated and compared with respect to their effectiveness in extracting the relevant information from video recordings. Results obtained are compared with those recorded by a modern commercial finger pulse oximeter. It is found that ICA produces the most consistent results.

Targeting dysfunctional beta-cell signaling for the potential treatment of type 1 diabetes mellitus.

Science.gov (United States)

Fenske, Rachel J; Kimple, Michelle E

2018-03-01

Since its discovery and purification by Frederick Banting in 1921, exogenous insulin has remained almost the sole therapy for type 1 diabetes mellitus. While insulin alleviates the primary dysfunction of the disease, many other aspects of the pathophysiology of type 1 diabetes mellitus are unaffected. Research aimed towards the discovery of novel type 1 diabetes mellitus therapeutics targeting different cell signaling pathways is gaining momentum. The focus of these efforts has been almost entirely on the impact of immunomodulatory drugs, particularly those that have already received FDA-approval for other autoimmune diseases. However, these drugs can often have severe side effects, while also putting already immunocompromised individuals at an increased risk for other infections. Potential therapeutic targets in the insulin-producing beta-cell have been largely ignored by the type 1 diabetes mellitus field, save the glucagon-like peptide 1 receptor. While there is preliminary evidence to support the clinical exploration of glucagon-like peptide 1 receptor-based drugs as type 1 diabetes mellitus adjuvant therapeutics, there is a vast space for other putative therapeutic targets to be explored. The alpha subunit of the heterotrimeric G z protein (Gα z ) has been shown to promote beta-cell inflammation, dysfunction, death, and failure to replicate in the context of diabetes in a number of mouse models. Genetic loss of Gα z or inhibition of the Gα z signaling pathway through dietary interventions is protective against the development of insulitis and hyperglycemia. The multifaceted effects of Gα z in regards to beta-cell health in the context of diabetes make it an ideal therapeutic target for further study. It is our belief that a low-risk, effective therapy for type 1 diabetes mellitus will involve a multidimensional approach targeting a number of regulatory systems, not the least of which is the insulin-producing beta-cell. Impact statement The expanding

High-protein diet modifies colonic microbiota and luminal environment but not colonocyte metabolism in the rat model: the increased luminal bulk connection.

Science.gov (United States)

Liu, Xinxin; Blouin, Jean-Marc; Santacruz, Arlette; Lan, Annaïg; Andriamihaja, Mireille; Wilkanowicz, Sabina; Benetti, Pierre-Henri; Tomé, Daniel; Sanz, Yolanda; Blachier, François; Davila, Anne-Marie

2014-08-15

High-protein diets are used for body weight reduction, but consequences on the large intestine ecosystem are poorly known. Here, rats were fed for 15 days with either a normoproteic diet (NP, 14% protein) or a hyperproteic-hypoglucidic isocaloric diet (HP, 53% protein). Cecum and colon were recovered for analysis. Short- and branched-chain fatty acids, as well as lactate, succinate, formate, and ethanol contents, were markedly increased in the colonic luminal contents of HP rats (P diet, whereas the amount of butyrate in feces was increased (P diet consumption allows maintenance in the luminal butyrate concentration and thus its metabolism in colonocytes despite modified microbiota composition and increased substrate availability. Copyright © 2014 the American Physiological Society.

A pro-cathepsin L mutant is a luminal substrate for endoplasmic-reticulum-associated degradation in C. elegans.

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Mark T Miedel

Full Text Available Endoplasmic-reticulum associated degradation (ERAD is a major cellular misfolded protein disposal pathway that is well conserved from yeast to mammals. In yeast, a mutant of carboxypeptidase Y (CPY* was found to be a luminal ER substrate and has served as a useful marker to help identify modifiers of the ERAD pathway. Due to its ease of genetic manipulation and the ability to conduct a genome wide screen for modifiers of molecular pathways, C. elegans has become one of the preferred metazoans for studying cell biological processes, such as ERAD. However, a marker of ERAD activity comparable to CPY* has not been developed for this model system. We describe a mutant of pro-cathepsin L fused to YFP that no longer targets to the lysosome, but is efficiently eliminated by the ERAD pathway. Using this mutant pro-cathepsin L, we found that components of the mammalian ERAD system that participate in the degradation of ER luminal substrates were conserved in C. elegans. This transgenic line will facilitate high-throughput genetic or pharmacological screens for ERAD modifiers using widefield epifluorescence microscopy.

Signal and data processing of small targets 1989; Proceedings of the Meeting, Orlando, FL, Mar. 27-29, 1989

Science.gov (United States)

Drummond, Oliver E. (Editor)

1989-01-01

The present conference on digital signal processing, association and filtering techniques, and multiple-sensor/multiple-tracking techniques, discusses single-frame velocity estimation, efficient target extraction for laser radar imagery, precision target tracking for small extended objects, IR clutter partitioning for matched filter design, the maximum-likelihood approach to gamma circumvention, position estimation for optical point targets using staring detector arrays, and a multiple-scan signal processing technique for area-moving target indication. Also discussed are a proportional integral estimator, the prediction of track purity in tracking performance evaluations, synchronization and fault-tolerance in a distributed tracker, the benefits of soft sensors and probabilistic fusion, and testing track initiation algorithms fusing two-dimensional tracks.

NMR signal analysis in the large COMPASS $^{14}$NH$_{3}$ target

CERN Document Server

Koivuniemi, J; Hess, C; Kisselev, Y U; Meyer, W; Radtke, E; Reicherz, G; Doshita, N; Iwata, T; Kondo, K; Michigami, T

2009-01-01

In the large COMPASS polarized proton target the 1508 cm$^{3}$ of irradiated granular ammonia is polarized with dynamic nuclear polarization method using 4 mm microwaves in 2.5 T eld. The nuclear polarization up to 90 - 93 % is determined with cw NMR. The properties of the observed ammonia proton signals are described and spin thermodynamics in high elds is presented. Also the second moment of the NMR line is estimated.

SPECIFIC CHARACTERISTICS OF BRAIN METASTASIZING IN PATIENTS WITH LUMINAL SUBTYPE OF BREAST CANCER

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A. S. Balkanov

2016-01-01

Full Text Available Background: More than half of female patients with breast cancer are diagnosed with a  luminal subtype of the disease; however, specific characteristics of its metastases to the brain have been not well studied, unlike those of HER2 positive and triple negative subtypes. Aim: A  comparative analysis of characteristics of metastatic brain lesions in patients with luminal breast cancer. Materials and methods: The time from surgery for breast cancer to the first recurrence and to metastatic brain lesions (assessed by contrast-enhanced MRI imaging was measured in 41 patients with luminal subtype of breast cancer (median age, 49.5±9.6  years, depending on a  diameter of the primary tumor and numbers of involved axillary lymph nodes. Results: The time interval to occurrence of brain metastases in luminal subtype of breast cancer is not associated with the size of the tumor. If≥4  axillary lymph nodes are involved (N2–3, brain metastases are identified much earlier (p<0.05 than in patients with N0–1 (34.5±23.9 months and 62.7±50 months, respectively. Neither the size nor the involvement of axillary lymph nodes has any impact on the rates of metastatic lesion to the brain during the first recurrence. Conclusion: Brain metastases occur at a much shorter time in those patients of luminal subtype of breast cancer who have metastases in≥4  axillary lymph nodes. Brain metastases develop in 50% of patients with the first recurrence of the luminal subtype of breast cancer.

["Glare vision". I. Physiological principles of vision change with increased test field luminance].

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Hauser, B; Ochsner, H; Zrenner, E

1992-02-01

Clinical tests of visual acuity are an important measure of visual function. However visual acuity is usually determined only in narrow range of luminance levels between 160 and 320 cd/m2; therefore losses of visual acuity in other ranges of light intensity can not be detected. In a distance of 80 cm from the patients eyes, Landolt rings of varying sizes were presented on a small test field whose light intensity can be varied between 0.1 and 30,000 cd/m2. Thereby an acuity-luminance-function can be obtained. We studied such functions under different conditions of exposure time both with constant and with increasing luminance of the test field. We found that persons with normal vision can increase their visual acuity with increasing test field luminance up to a range of 5000 cd/m2. The maximum values of visual acuity under optimal lightening conditions lie (varying with age) between 2.2 and 0.9. Under pathological conditions visual acuity falls at high luminances accompanied by sensations of glare. Tests of glare sensitivity as a function of exposure time showed 4 sec to be a critical time of exposure since after 4 sec normal persons just reach their maximum visual acuity at high luminances. The underlying physiological mechanisms lead us to suppose that patients with neuronal light adaptation disturbances display a greater visual loss as a result of decreased time of exposure than those with disturbances in the ocular media. Visual acuity as well as the capacity to increase the patients visual acuity under optimal conditions of lighting were both found to be strongly age-dependent.(ABSTRACT TRUNCATED AT 250 WORDS)

Signal and data processing of small targets 1992; Proceedings of the Meeting, Orlando, FL, Apr. 20-22, 1992

Science.gov (United States)

Drummond, Oliver E.

This volume on signal and data processing of small targets contains chapters devoted to signal processing, low observable detection, systems and simulations, association and filtering in tracking, multiple sensor processing and fusion, and data processing. Papers included are on multisensor predetection fusion, adaptive whitening filters for small target detection, unified framework for IR target detection and tracking, and target detection from image sequences using pixel-based decision criterion. Attention is also given to automatic acquisition and tracking of rounds and targets for electrooptic fire control, advanced surveillance testbed and background modeling, an interacting-multiple-model algorithm for tracking targets that maneuver through coordinated turns, and angular momentum and ballistic tracking. Other papers are on a data integration (fusion) tree paradigm, single-scan tracking using N IR sensors, and track monitoring with single and multiple 2D passive sensors. (No individual items are abstracted in this volume)

Epimorphin mediates mammary luminal morphogenesis through control of C/EBPbeta

International Nuclear Information System (INIS)

Hirai, Yohei; Radisky, Derek; Boudreau, Rosanne; Simian, Marina; Stevens, Mary E.; Oka, Yumiko; Takebe, Kyoko; Niwa, Shinichiro; Bissell, Mina J.

2002-01-01

We have previously shown that epimorphin, a protein expressed on the surface of myoepithelial and fibroblast cells of the mammary gland, acts as a multifunctional morphogen of mammary epithelial cells. Here, we present the molecular mechanism by which epimorphin mediates luminal morphogenesis. Treatment of cells with epimorphin to induce lumen formation greatly increases the overall expression of transcription factor CCAAT/enhancer binding protein beta (C/EBPbeta) and alters the relative expression of its two principal isoforms, LIP and LAP. These alterations were shown to be essential for the morphogenetic activities, as constitutive expression of LIP was sufficient to produce lumen formation, while constitutive expression of LAP blocked epimorphin-mediated luminal morphogenesis. Furthermore, in a transgenic mouse model in which epimorphin expression was expressed in an apolar fashion on the surface of mammary epithelial cells, we found increased expression of C/EBPbeta, increased relative expression of LIP to LAP, and enlarged ductal lumina. Together, our studies demonstrate a role for epimorphin in luminal morphogenesis through control of C/EBPbeta expression

Signal and data processing of small targets 1991; Proceedings of the Meeting, Orlando, FL, Apr. 1-3, 1991

Science.gov (United States)

Drummond, Oliver E.

Attention is given to signal processing; track-before-detect; systems and simulations; association and filtering in tracking; and data processing. Particular attention is given to a linear modeling algorithm for tracking time-varying signals, an optoelectric Gabor detector for transient signals, small-target acquisition and typing by AASAP, model-based analysis of 3D spatial-temporal IR clutter suppression filtering, algorithms and architectures for implementing large-velocity filter banks, an end-to-end scenario-generating model for IRST performance analysis, detection and tracking of small targets in persistence, an incremental model for target maneuver estimation, implementation of an angle-only tracking filter, a global modeling approach for multisensor problems, passive-sensor data fusion, midcourse multitarget racking using continuous representation, neural data association, and statistical initial orbit determination. (For individual items see A93-26797 to A93-26799)

Evaluating the Influence of Chromatic and Luminance Stimuli on SSVEPs from Behind-the-Ears and Occipital Areas

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Alan Floriano

2018-02-01

Full Text Available This work presents a study of chromatic and luminance stimuli in low-, medium-, and high-frequency stimulation to evoke steady-state visual evoked potential (SSVEP in the behind-the-ears area. Twelve healthy subjects participated in this study. The electroencephalogram (EEG was measured on occipital (Oz and left and right temporal (TP9 and TP10 areas. The SSVEP was evaluated in terms of amplitude, signal-to-noise ratio (SNR, and detection accuracy using power spectral density analysis (PSDA, canonical correlation analysis (CCA, and temporally local multivariate synchronization index (TMSI methods. It was found that stimuli based on suitable color and luminance elicited stronger SSVEP in the behind-the-ears area, and that the response of the SSVEP was related to the flickering frequency and the color of the stimuli. Thus, green-red stimulus elicited the highest SSVEP in medium-frequency range, and green-blue stimulus elicited the highest SSVEP in high-frequency range, reaching detection accuracy rates higher than 80%. These findings will aid in the development of more comfortable, accurate and stable BCIs with electrodes positioned on the behind-the-ears (hairless areas.

In Vivo Phosphoproteomics Analysis Reveals the Cardiac Targets of β-Adrenergic Receptor Signaling

DEFF Research Database (Denmark)

Lundby, Alicia; Andersen, Martin N; Steffensen, Annette B

2013-01-01

β-Blockers are widely used to prevent cardiac arrhythmias and to treat hypertension by inhibiting β-adrenergic receptors (βARs) and thus decreasing contractility and heart rate. βARs initiate phosphorylation-dependent signaling cascades, but only a small number of the target proteins are known. We...

Optical system for a universal luminance meter

NARCIS (Netherlands)

Schreuder, D.A.

1965-01-01

There is a need for luminance meters in various fields of photometry having these characteristics: a- objective method of measurements. b. variable shape and size of measurement area. c- absence of parallax during aiming operations. d- Possibility of observing the part of the field of view to be

Genome-wide identification of Bcl11b gene targets reveals role in brain-derived neurotrophic factor signaling.

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Bin Tang

Full Text Available B-cell leukemia/lymphoma 11B (Bcl11b is a transcription factor showing predominant expression in the striatum. To date, there are no known gene targets of Bcl11b in the nervous system. Here, we define targets for Bcl11b in striatal cells by performing chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq in combination with genome-wide expression profiling. Transcriptome-wide analysis revealed that 694 genes were significantly altered in striatal cells over-expressing Bcl11b, including genes showing striatal-enriched expression similar to Bcl11b. ChIP-seq analysis demonstrated that Bcl11b bound a mixture of coding and non-coding sequences that were within 10 kb of the transcription start site of an annotated gene. Integrating all ChIP-seq hits with the microarray expression data, 248 direct targets of Bcl11b were identified. Functional analysis on the integrated gene target list identified several zinc-finger encoding genes as Bcl11b targets, and further revealed a significant association of Bcl11b to brain-derived neurotrophic factor/neurotrophin signaling. Analysis of ChIP-seq binding regions revealed significant consensus DNA binding motifs for Bcl11b. These data implicate Bcl11b as a novel regulator of the BDNF signaling pathway, which is disrupted in many neurological disorders. Specific targeting of the Bcl11b-DNA interaction could represent a novel therapeutic approach to lowering BDNF signaling specifically in striatal cells.

Measurements of the global 21-cm signal from the Cosmic Dawn

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Bernardi, Gianni

2018-05-01

The sky-averaged (global) 21-cm signal is a very promising probe of the Cosmic Dawn, when the first luminous sources were formed and started to shine in a substantially neutral intergalactic medium. I here report on the status and early result of the Large-Aperture Experiment to Detect the Dark Age that focuses on observations of the global 21-cm signal in the 16 <~ z <~ 30 range.

Sensitivity analysis of intracellular signaling pathway kinetics predicts targets for stem cell fate control.

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Alborz Mahdavi

2007-07-01

Full Text Available Directing stem cell fate requires knowledge of how signaling networks integrate temporally and spatially segregated stimuli. We developed and validated a computational model of signal transducer and activator of transcription-3 (Stat3 pathway kinetics, a signaling network involved in embryonic stem cell (ESC self-renewal. Our analysis identified novel pathway responses; for example, overexpression of the receptor glycoprotein-130 results in reduced pathway activation and increased ESC differentiation. We used a systematic in silico screen to identify novel targets and protein interactions involved in Stat3 activation. Our analysis demonstrates that signaling activation and desensitization (the inability to respond to ligand restimulation is regulated by balancing the activation state of a distributed set of parameters including nuclear export of Stat3, nuclear phosphatase activity, inhibition by suppressor of cytokine signaling, and receptor trafficking. This knowledge was used to devise a temporally modulated ligand delivery strategy that maximizes signaling activation and leads to enhanced ESC self-renewal.

The effects of luminance contribution from large fields to chromatic visual evoked potentials.

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Skiba, Rafal M; Duncan, Chad S; Crognale, Michael A

2014-02-01

Though useful from a clinical and practical standpoint uniform, large-field chromatic stimuli are likely to contain luminance contributions from retinal inhomogeneities. Such contribution can significantly influence psychophysical thresholds. However, the degree to which small luminance artifacts influence the chromatic VEP has been debated. In particular, claims have been made that band-pass tuning observed in chromatic VEPs result from luminance intrusion. However, there has been no direct evidence presented to support these claims. Recently, large-field isoluminant stimuli have been developed to control for intrusion from retinal inhomogeneities with particular regard to the influence of macular pigment. We report here the application of an improved version of these full-field stimuli to directly test the influence of luminance intrusion on the temporal tuning of the chromatic VEP. Our results show that band-pass tuning persists even when isoluminance is achieved throughout the extent of the stimulus. In addition, small amounts of luminance intrusion affect neither the shape of the temporal tuning function nor the major components of the VEP. These results support the conclusion that the chromatic VEP can depart substantially from threshold psychophysics with regard to temporal tuning and that obtaining a low-pass function is not requisite evidence of selective chromatic activation in the VEP. Copyright © 2013 Elsevier Ltd. All rights reserved.

[Cell signaling pathways interaction in cellular proliferation: Potential target for therapeutic interventionism].

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Valdespino-Gómez, Víctor Manuel; Valdespino-Castillo, Patricia Margarita; Valdespino-Castillo, Víctor Edmundo

2015-01-01

Nowadays, cellular physiology is best understood by analysing their interacting molecular components. Proteins are the major components of the cells. Different proteins are organised in the form of functional clusters, pathways or networks. These molecules are ordered in clusters of receptor molecules of extracellular signals, transducers, sensors and biological response effectors. The identification of these intracellular signaling pathways in different cellular types has required a long journey of experimental work. More than 300 intracellular signaling pathways have been identified in human cells. They participate in cell homeostasis processes for structural and functional maintenance. Some of them participate simultaneously or in a nearly-consecutive progression to generate a cellular phenotypic change. In this review, an analysis is performed on the main intracellular signaling pathways that take part in the cellular proliferation process, and the potential use of some components of these pathways as target for therapeutic interventionism are also underlined. Copyright © 2015 Academia Mexicana de Cirugía A.C. Published by Masson Doyma México S.A. All rights reserved.

Magnolin inhibits cell migration and invasion by targeting the ERKs/RSK2 signaling pathway

International Nuclear Information System (INIS)

Lee, Cheol-Jung; Lee, Mee-Hyun; Yoo, Sun-Mi; Choi, Kyung-Il; Song, Ji-Hong; Jang, Jeong-Hoon; Oh, Sei-Ryang; Ryu, Hyung-Won; Lee, Hye-Suk; Surh, Young-Joon; Cho, Yong-Yeon

2015-01-01

Magnolin is a natural compound abundantly found in Magnolia flos, which has been traditionally used in oriental medicine to treat headaches, nasal congestion and anti-inflammatory reactions. Our recent results have demonstrated that magnolin targets the active pockets of ERK1 and ERK2, which are important signaling molecules in cancer cell metastasis. The aim of this study is to evaluate the effects of magnolin on cell migration and to further explore the molecular mechanisms involved. Magnolin-mediated signaling inhibition was confirmed by Western blotting using RSK2 +/+ and RSK2 −/− MEFs, A549 and NCI-H1975 lung cancer cells, and by NF-κB and Cox-2 promoter luciferase reporter assays. Inhibition of cell migration by magnolin was examined by wound healing and/or Boyden Chamber assays using JB6 Cl41 and A549 human lung cancer cells. The molecular mechanisms involved in cell migration and epithelial-to-mesenchymal transition were determined by zymography, Western blotting, real-time PCR and immunocytofluorescence. Magnolin inhibited NF-κB transactivation activity by suppressing the ERKs/RSK2 signaling pathway. Moreover, magnolin abrogated the increase in EGF-induced COX-2 protein levels and wound healing. In human lung cancer cells such as A549 and NCI-H1975, which harbor constitutive active Ras and EGFR mutants, respectively, magnolin suppressed wound healing and cell invasion as seen by a Boyden chamber assay. In addition, it was observed that magnolin inhibited MMP-2 and −9 gene expression and activity. The knockdown or knockout of RSK2 in A549 lung cancer cells or MEFs revealed that magnolin targeting ERKs/RSK2 signaling suppressed epithelial-to-mesenchymal transition by modulating EMT marker proteins such as N-cadherin, E-cadherin, Snail, Vimentin and MMPs. These results demonstrate that magnolin inhibits cell migration and invasion by targeting the ERKs/RSK2 signaling pathway. The online version of this article (doi:10.1186/s12885-015-1580-7) contains

Prolactin suppresses a progestin-induced CK5-positive cell population in luminal breast cancer through inhibition of progestin-driven BCL6 expression

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Sato, Takahiro; Tran, Thai H.; Peck, Amy R.; Girondo, Melanie A.; Liu, Chengbao; Goodman, Chelain R.; Neilson, Lynn M.; Freydin, Boris; Chervoneva, Inna; Hyslop, Terry; Kovatich, Albert J.; Hooke, Jeffrey A.; Shriver, Craig D.; Fuchs, Serge Y.; Rui, Hallgeir

2014-01-01

Prolactin controls the development and function of milk-producing breast epithelia but also supports growth and differentiation of breast cancer, especially luminal subtypes. A principal signaling mediator of prolactin, Stat5, promotes cellular differentiation of breast cancer cells in vitro, and loss of active Stat5 in tumors is associated with anti-estrogen therapy failure in patients. In luminal breast cancer progesterone induces a cytokeratin-5 (CK5)-positive basal cell-like population. This population possesses characteristics of tumor stem cells including quiescence, therapy-resistance, and tumor-initiating capacity. Here we report that prolactin counteracts induction of the CK5-positive population by the synthetic progestin R5020 in luminal breast cancer cells both in vitro and in vivo. CK5-positive cells were chemoresistant as determined by four-fold reduced rate of apoptosis following docetaxel exposure. Progestin-induction of CK5 was preceded by marked up-regulation of BCL6, an oncogene and transcriptional repressor critical for the maintenance of leukemia-initiating cells. Knockdown of BCL6 prevented induction of CK5-positive cell population by progestin. Prolactin suppressed progestin-induced BCL6 through Jak2-Stat5 but not Erk- or Akt-dependent pathways. In premenopausal but not postmenopausal patients with hormone receptor-positive breast cancer, tumor protein levels of CK5 correlated positively with BCL6, and high BCL6 or CK5 protein levels were associated with unfavorable clinical outcome. Suppression of progestin-induction of CK5-positive cells represents a novel pro-differentiation effect of prolactin in breast cancer. The present progress may have direct implications for breast cancer progression and therapy since loss of prolactin receptor-Stat5 signaling occurs frequently and BCL6 inhibitors currently being evaluated for lymphomas may have value for breast cancer. PMID:23708665

To fingolimod and beyond: The rich pipeline of drug candidates that target S1P signaling.

Science.gov (United States)

Chew, Wee Siong; Wang, Wei; Herr, Deron R

2016-11-01

Sphingosine 1-phosphate (S1P) is an extracellular lipid signaling molecule that acts as a selective, high-affinity ligand for a family of five G protein-coupled receptors. This signaling system was first identified twenty years ago, and has since been shown to regulate a diverse range of physiological processes and disease states, such as cardiovascular development, immune function, hypoxic responses, and cancer. The therapeutic potential of targeting this system took center stage when it was demonstrated that the immune modulator, fingolimod (FTY720/Gilenya), exerts it lymphopenic effect by acting on S1P receptors, primarily on S1P receptor 1 (S1P 1 ). In 2010, fingolimod became the first oral medication approved for the treatment of multiple sclerosis (MS). Since then, second-generation S1P receptor modulators have been under development in an effort to provide improved safety and efficacy profiles for MS, and to broaden their use to other autoimmune indications. Beyond the development of S1P 1 -modulators, there has been considerable effort in targeting other components of the S1P signaling pathway for the treatment of other diseases, such as cardiovascular disease, sepsis, and cancer. This manuscript provides an overview of the clinical and preclinical development of drugs targeting S1P signaling. Copyright © 2016 Elsevier Ltd. All rights reserved.

Maturation of polarization and luminance contrast sensitivities in cuttlefish (Sepia officinalis).

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Cartron, Lelia; Dickel, Ludovic; Shashar, Nadav; Darmaillacq, Anne-Sophie

2013-06-01

Polarization sensitivity is a characteristic of the visual system of cephalopods. It has been well documented in adult cuttlefish, which use polarization sensitivity in a large range of tasks such as communication, orientation and predation. Because cuttlefish do not benefit from parental care, their visual system (including the ability to detect motion) must be efficient from hatching to enable them to detect prey or predators. We studied the maturation and functionality of polarization sensitivity in newly hatched cuttlefish. In a first experiment, we examined the response of juvenile cuttlefish from hatching to the age of 1 month towards a moving, vertically oriented grating (contrasting and polarized stripes) using an optomotor response apparatus. Cuttlefish showed differences in maturation of polarization versus luminance contrast motion detection. In a second experiment, we examined the involvement of polarization information in prey preference and detection in cuttlefish of the same age. Cuttlefish preferentially chose not to attack transparent prey whose polarization contrast had been removed with a depolarizing filter. Performances of prey detection based on luminance contrast improved with age. Polarization contrast can help cuttlefish detect transparent prey. Our results suggest that polarization is not a simple modulation of luminance information, but rather that it is processed as a distinct channel of visual information. Both luminance and polarization sensitivity are functional, though not fully matured, in newly hatched cuttlefish and seem to help in prey detection.

Wavelength and ambient luminance dependence of laser eye dazzle.

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Williamson, Craig A; McLin, Leon N; Rickman, J Michael; Manka, Michael A; Garcia, Paul V; Kinerk, Wesley T; Smith, Peter A

2017-10-10

A series of experiments has been conducted to quantify the effects of laser wavelength and ambient luminance on the severity of laser eye dazzle experienced by human subjects. Eight laser wavelengths in the visible spectrum were used (458-647 nm) across a wide range of ambient luminance conditions (0.1-10,000  cd·m -2 ). Subjects were exposed to laser irradiance levels up to 600  μW·cm -2 and were asked to recognize the orientation of optotypes at varying eccentricities up to 31.6 deg of visual angle from the laser axis. More than 40,000 data points were collected from 14 subjects (ages 23-64), and these were consolidated into a series of obscuration angles for comparison to a theoretical model of laser eye dazzle. Scaling functions were derived to allow the model to predict the effects of laser dazzle on vision more accurately by including the effects of ambient luminance and laser wavelength. The updated model provides an improved match to observed laser eye dazzle effects across the full range of conditions assessed. The resulting model will find use in a variety of laser safety applications, including the estimation of maximum dazzle exposure and nominal ocular dazzle distance values.

The watercolor effect: quantitative evidence for luminance-dependent mechanisms of long-range color assimilation.

Science.gov (United States)

Devinck, Frédéric; Delahunt, Peter B; Hardy, Joseph L; Spillmann, Lothar; Werner, John S

2005-05-01

When a dark chromatic contour delineating a figure is flanked on the inside by a brighter chromatic contour, the brighter color will spread into the entire enclosed area. This is known as the watercolor effect (WCE). Here we quantified the effect of color spreading using both color-matching and hue-cancellation tasks. Over a wide range of stimulus chromaticities, there was a reliable shift in color appearance that closely followed the direction of the inducing contour. When the contours were equated in luminance, the WCE was still present, but weak. The magnitude of the color spreading increased with increases in luminance contrast between the two contours. Additionally, as the luminance contrast between the contours increased, the chromaticity of the induced color more closely resembled that of the inside contour. The results support the hypothesis that the WCE is mediated by luminance-dependent mechanisms of long-range color assimilation.

Luminal and basolateral uptake of insulin in isolated perfused, proximal tubules

International Nuclear Information System (INIS)

Nielsen, S.; Nielsen, J.T.; Christensen, E.I.

1987-01-01

The present study was performed to quantitate compare the luminal and the peritubular uptake of 125 I-insulin in isolated, perfused, proximal tubules from rabbit kidneys. 125 I-insulin was added in physiological concentrations to either the perfusate or the bath fluid for 30 min. The luminal uptake in 30 min averaged 0.76 pg/mm at physiological concentrations and 18.0 pg/mm at high insulin concentrations. About 15-41% of the absorbed insulin was digested and 125 I-insulin at physiological and high concentrations in the bath was 0.136 and 0.318 pg, respectively. The data indicates that insulin is bound/absorbed at the basolateral membranes both by a saturable specific mechanism and a nonspecific, nonsaturable mechanism. The basolateral absorption constituted 15.2 and 1.8% of the total tubular extraction of insulin at physiological and high insulin concentrations, respectively. Electron microscope autoradiography showed that, after luminal as well as basolateral endocytosis, insulin was exclusively accumulated in endocytic vacuoles and lysosomes

DOA Estimation of Low Altitude Target Based on Adaptive Step Glowworm Swarm Optimization-multiple Signal Classification Algorithm

Directory of Open Access Journals (Sweden)

Zhou Hao

2015-06-01

Full Text Available The traditional MUltiple SIgnal Classification (MUSIC algorithm requires significant computational effort and can not be employed for the Direction Of Arrival (DOA estimation of targets in a low-altitude multipath environment. As such, a novel MUSIC approach is proposed on the basis of the algorithm of Adaptive Step Glowworm Swarm Optimization (ASGSO. The virtual spatial smoothing of the matrix formed by each snapshot is used to realize the decorrelation of the multipath signal and the establishment of a fullorder correlation matrix. ASGSO optimizes the function and estimates the elevation of the target. The simulation results suggest that the proposed method can overcome the low altitude multipath effect and estimate the DOA of target readily and precisely without radar effective aperture loss.

Prognostic Significance of Progesterone Receptor–Positive Tumor Cells Within Immunohistochemically Defined Luminal A Breast Cancer

Science.gov (United States)

Prat, Aleix; Cheang, Maggie Chon U.; Martín, Miguel; Parker, Joel S.; Carrasco, Eva; Caballero, Rosalía; Tyldesley, Scott; Gelmon, Karen; Bernard, Philip S.; Nielsen, Torsten O.; Perou, Charles M.

2013-01-01

Purpose Current immunohistochemical (IHC)-based definitions of luminal A and B breast cancers are imperfect when compared with multigene expression-based assays. In this study, we sought to improve the IHC subtyping by examining the pathologic and gene expression characteristics of genomically defined luminal A and B subtypes. Patients and Methods Gene expression and pathologic features were collected from primary tumors across five independent cohorts: British Columbia Cancer Agency (BCCA) tamoxifen-treated only, Grupo Español de Investigación en Cáncer de Mama 9906 trial, BCCA no systemic treatment cohort, PAM50 microarray training data set, and a combined publicly available microarray data set. Optimal cutoffs of percentage of progesterone receptor (PR) –positive tumor cells to predict survival were derived and independently tested. Multivariable Cox models were used to test the prognostic significance. Results Clinicopathologic comparisons among luminal A and B subtypes consistently identified higher rates of PR positivity, human epidermal growth factor receptor 2 (HER2) negativity, and histologic grade 1 in luminal A tumors. Quantitative PR gene and protein expression were also found to be significantly higher in luminal A tumors. An empiric cutoff of more than 20% of PR-positive tumor cells was statistically chosen and proved significant for predicting survival differences within IHC-defined luminal A tumors independently of endocrine therapy administration. Finally, no additional prognostic value within hormonal receptor (HR) –positive/HER2-negative disease was observed with the use of the IHC4 score when intrinsic IHC-based subtypes were used that included the more than 20% PR-positive tumor cells and vice versa. Conclusion Semiquantitative IHC expression of PR adds prognostic value within the current IHC-based luminal A definition by improving the identification of good outcome breast cancers. The new proposed IHC-based definition of luminal A

Target of rapamycin signalling mediates the lifespan-extending effects of dietary restriction by essential amino acid alteration

NARCIS (Netherlands)

Emran, S.; Yang, M.Y.; He, X.L.; Zandveld, J.; Piper, M.D.W.

2014-01-01

Dietary restriction (DR), defined as a moderate reduction in food intake short of malnutrition, has been shown to extend healthy lifespan in a diverse range of organisms, from yeast to primates. Reduced signalling through the insulin/IGF-like (IIS) and Target of Rapamycin (TOR) signalling pathways

Histone 2B-GFP Label-Retaining Prostate Luminal Cells Possess Progenitor Cell Properties and Are Intrinsically Resistant to Castration

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Dingxiao Zhang

2018-01-01

Full Text Available The existence of slow-cycling luminal cells in the prostate has been suggested, but their identity and functional properties remain unknown. Using a bigenic mouse model to earmark, isolate, and characterize the quiescent stem-like cells, we identify a label-retaining cell (LRC population in the luminal cell layer as luminal progenitors. Molecular and biological characterizations show that these luminal LRCs are significantly enriched in the mouse proximal prostate, exhibit relative dormancy, display bipotency in both in vitro and in vivo assays, and express a stem/progenitor gene signature with resemblance to aggressive prostate cancer. Importantly, these LRCs, compared with bulk luminal cells, maintain a lower level of androgen receptor (AR expression and are less androgen dependent and also castration resistant in vivo. Finally, analysis of phenotypic markers reveals heterogeneity within the luminal progenitor cell pool. Our study establishes luminal LRCs as progenitors that may serve as a cellular origin for castration-resistant prostate cancer.

Signal Transduction and Molecular Targets of Selected Flavonoids

Science.gov (United States)

Bode, Ann M.

2013-01-01

Abstract Significance: Diet exerts a major influence on the risk for developing cancer and heart disease. Food factors such as flavonoids are alleged to protect cells from premature aging and disease by shielding DNA, proteins, and lipids from oxidative damage. Recent Advances: Our work has focused on clarifying the effects of dietary components on cancer cell proliferation and tumor growth, discovering mechanisms to explain the effects, and identifying the specific molecular targets of these compounds. Our strategy for identifying specific molecular targets of phytochemicals involves the use of supercomputer technology combined with protein crystallography, molecular biology, and experimental laboratory verification. Critical Issues: One of the greatest challenges for scientists is to reduce the accumulation of distortion and half truths reported in the popular media regarding the health benefits of certain foods or food supplements. The use of these is not new, but interest has increased dramatically because of perceived health benefits that are presumably acquired without unpleasant side effects. Flavonoids are touted to exert many beneficial effects in vitro. However, whether they can produce these effects in vivo is disputed. Future Directions: The World Health Organization indicates that one third of all cancer deaths are preventable and that diet is closely linked to prevention. Based on this idea and epidemiological findings, attention has centered on dietary phytochemicals as an effective intervention in cancer development. However, an unequivocal link between diet and cancer has not been established. Thus, identifying cancer preventive dietary agents with specific molecular targets is essential to move forward toward successful cancer prevention. Antioxid. Redox Signal. 19, 163–180. PMID:23458437

A new interpretation of luminous blue stars

International Nuclear Information System (INIS)

Stothers, R.

1976-01-01

A major revision of current theoretical ideas about the brightest blue stars must be made if Carson's new radiative opacities are adopted in stellar models. Unlike earlier opacities, the new opacities exhibit a large ''bump'' due to CNO ionization, which leads to very strong central condensation, convective instability, and pulsational instability in hot, diffuse stellar envelopes (typically those in which L/M>10 3 solar units). Despite a number of theoretical uncertainties, the new picture of the structure of very luminous stars is reasonably successful in accounting for a variety of previously unexplained observations. Thus, the new stellar models for the phase of core hydrogen burning predict large radii and rather cool effective temperatures (which are yet to be observationally confirmed) for O stars, and a spreading out of the main-sequence band in the H-R diagram toward luminous cool supergiants for masses higher than approx.20 M/sub sun/, beginning at M/sub v/=-4.5 and Sp=B1. They also predict slower surface rotations for O stars compared with B stars; and, in binary systems, slower apsidal motions, closer rotational-revolutional synchronism, and smaller orbital eccentricities. In massive X-ray binary systems, circular orbits and supergiant-like visual companions are expected to be quite common. Radial pulsations of the models have been calculated by employing linearized nonadiabatic pulsation theory. Long-period variability is predicted to exist for massive blue supergiants of luminosity class Ia. The new models for helium stars predict large radii and rather cool effective temperatures for Wolf-Rayet stars, as well as multimodal pulsational instability and, possibly, surface turbulence for these stars. Ultrashort-period variability, observed in many classes of hot luminous stars, may be due, in part, to high radial overtone pulsations (or, possibly, to nonradial pulsation or convective modes)

Defining optimal duration and predicting benefit from chemotherapy in patients with luminal-like subtypes.

Science.gov (United States)

Hart, Christopher D; Sanna, Giuseppina; Siclari, Olimpia; Biganzoli, Laura; Di Leo, Angelo

2015-11-01

The molecular subtypes of breast cancer have individual patterns of behaviour, prognosis and sensitivity to treatment, with subsequent implications for the choice of, or indeed role for adjuvant therapy. The luminal A and B subtypes make up the majority of breast cancers, but despite sharing expression of the oestrogen receptor (ER), they are molecularly distinct. It follows then that they would have different sensitivities to chemotherapy. Clinically, luminal A disease has a better prognosis than luminal B, and may not derive significant benefit from adjuvant chemotherapy. However no prospective trials have specifically investigated the benefit of adjuvant chemotherapy in each subtype, nor do we know if certain agents are more or less effective. This paper will briefly summarise the role of molecular profiles in assessing the need for chemotherapy and predicting its effectiveness, followed by an assessment of the relative value of newer anthracycline- or taxane-containing regimes in the luminal-like subtypes, providing a review of retrospective analyses. Copyright © 2015 Elsevier Ltd. All rights reserved.

The Role of Cyclic Nucleotide Signaling Pathways in Cancer: Targets for Prevention and Treatment

Energy Technology Data Exchange (ETDEWEB)

Fajardo, Alexandra M.; Piazza, Gary A. [Drug Discovery Research Center, Mitchell Cancer Institute, University of South Alabama, 1660 Springhill Ave, Suite 3029, Mobile, AL 36604 (United States); Tinsley, Heather N., E-mail: htinsley@montevallo.edu [Department of Biology, Chemistry, and Mathematics, University of Montevallo, Station 6480, Montevallo, AL 35115 (United States)

2014-02-26

For more than four decades, the cyclic nucleotides cyclic AMP (cAMP) and cyclic GMP (cGMP) have been recognized as important signaling molecules within cells. Under normal physiological conditions, cyclic nucleotides regulate a myriad of biological processes such as cell growth and adhesion, energy homeostasis, neuronal signaling, and muscle relaxation. In addition, altered cyclic nucleotide signaling has been observed in a number of pathophysiological conditions, including cancer. While the distinct molecular alterations responsible for these effects vary depending on the specific cancer type, several studies have demonstrated that activation of cyclic nucleotide signaling through one of three mechanisms—induction of cyclic nucleotide synthesis, inhibition of cyclic nucleotide degradation, or activation of cyclic nucleotide receptors—is sufficient to inhibit proliferation and activate apoptosis in many types of cancer cells. These findings suggest that targeting cyclic nucleotide signaling can provide a strategy for the discovery of novel agents for the prevention and/or treatment of selected cancers.

Progression of urothelial carcinoma in situ of the urinary bladder: a switch from luminal to basal phenotype and related therapeutic implications.

Science.gov (United States)

Barth, Isabella; Schneider, Ursula; Grimm, Tobias; Karl, Alexander; Horst, David; Gaisa, Nadine T; Knüchel, Ruth; Garczyk, Stefan

2018-05-01

The stratification of bladder cancer into luminal and basal tumors has recently been introduced as a novel prognostic system in patient cohorts of muscle-invasive bladder cancer or high-grade papillary carcinomas. Using a representative immunohistochemistry panel, we analyzed luminal and basal marker expression in a large case series (n = 156) of urothelial carcinoma in situ (CIS), a precancerous lesion that frequently progresses to muscle-invasive disease. The majority of CIS cases was characterized by a positivity for luminal markers (aberrant cytokeratin (CK) 20 85% (132/156), GATA3 median Remmele score (score of staining intensity (0-3) multiplied with percentage of positive cells (0-4)): 12, estrogen receptor (ER) β Remmele score > 2: 88% (138/156), human epidermal growth factor receptor 2 (Her2) Dako score 3+ 32% (50/156), Her2 Dako score 2+ 33% (51/156)), and marginal expression of basal markers (CK5/6+ 2% (3/156), CK14+ 1% (2/156)). To further investigate phenotypic stability during disease progression, we compared 48 pairs of CIS and invasive tumors from the same biopsy. A highly significant loss of luminal marker expression (p < 0.001) was observed in the course of progression whereas an increase of basal marker expression (p < 0.01) was noted in the invasive compartment. Importantly, 91% of CIS cases demonstrated a positivity for at least one of the two predictive markers Her2 and ERβ, indicating that the analysis of Her2 and ERβ may help to identify CIS-patient subgroups prone to more efficient targeted treatment strategies. Larger prospective and biomarker-embedded clinical trials are needed to confirm and validate our preliminary findings.

cGMP signaling as a target for the prevention and treatment of breast cancer.

Science.gov (United States)

Windham, Perrin F; Tinsley, Heather N

2015-04-01

One in eight women in the United States will be diagnosed with invasive breast cancer in her lifetime. Advances in therapeutic strategies, diagnosis, and improved awareness have resulted in a significant reduction in breast cancer related mortality. However, there is a continued need for more effective and less toxic drugs for both the prevention and the treatment of breast cancer in order to see a continued decline in the morbidity and mortality associated with this disease. Recent studies suggest that the cGMP signaling pathway may be aberrantly regulated in breast cancer. As such, this pathway may serve as a source of novel targets for future breast cancer drug discovery efforts. This review provides an overview of cGMP signaling in normal physiology and in breast cancer as well as current strategies being investigated for targeting this pathway in breast cancer. Copyright © 2014 Elsevier Ltd. All rights reserved.

10 CFR 30.19 - Self-luminous products containing tritium, krypton-85, or promethium-147.

Science.gov (United States)

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false Self-luminous products containing tritium, krypton-85, or..., krypton-85, or promethium-147. (a) Except for persons who manufacture, process, produce, or initially transfer for sale or distribution self-luminous products containing tritium, krypton-85, or promethium-147...

High luminous flux from single crystal phosphor-converted laser-based white lighting system

KAUST Repository

Cantore, Michael; Pfaff, Nathan; Farrell, Robert M.; Speck, James S.; Nakamura, Shuji; DenBaars, Steven P.

2015-01-01

efficacy of 86.7 lm/W at 1.4 A and 4.24 V and a peak luminous flux of 1100 lm at 3.0 A and 4.85 V with a luminous efficacy of 75.6 lm/W. Simulations of a pc-LD confirm that the single crystal YAG:Ce sample did not experience thermal quenching at peak LD

Production of L-Asparaginase by the marine luminous bacteria

Digital Repository Service at National Institute of Oceanography (India)

Ramaiah, N.; Chandramohan, D.

Fortythree strains of luminous bacteria, belonging to 4 species, (Vibrio harveyi, V. fischeri, Photobacterium leiognathi and P. phosphoreum) isolated from different marine samples, were examined for the production of L-asparaginase. Presence...

Metabolic profiles of triple-negative and luminal A breast cancer subtypes in African-American identify key metabolic differences.

Science.gov (United States)

Tayyari, Fariba; Gowda, G A Nagana; Olopade, Olufunmilayo F; Berg, Richard; Yang, Howard H; Lee, Maxwell P; Ngwa, Wilfred F; Mittal, Suresh K; Raftery, Daniel; Mohammed, Sulma I

2018-02-20

Breast cancer, a heterogeneous disease with variable pathophysiology and biology, is classified into four major subtypes. While hormonal- and antibody-targeted therapies are effective in the patients with luminal and HER-2 subtypes, the patients with triple-negative breast cancer (TNBC) subtype do not benefit from these therapies. The incidence rates of TNBC subtype are higher in African-American women, and the evidence indicates that these women have worse prognosis compared to women of European descent. The reasons for this disparity remain unclear but are often attributed to TNBC biology. In this study, we performed metabolic analysis of breast tissues to identify how TNBC differs from luminal A breast cancer (LABC) subtypes within the African-American and Caucasian breast cancer patients, respectively. We used High-Resolution Magic Angle Spinning (HR-MAS) 1H Nuclear magnetic resonance (NMR) to perform the metabolomic analysis of breast cancer and adjacent normal tissues (total n=82 samples). TNBC and LABC subtypes in African American women exhibited different metabolic profiles. Metabolic profiles of these subtypes were also distinct from those revealed in Caucasian women. TNBC in African-American women expressed higher levels of glutathione, choline, and glutamine as well as profound metabolic alterations characterized by decreased mitochondrial respiration and increased glycolysis concomitant with decreased levels of ATP. TNBC in Caucasian women was associated with increased pyrimidine synthesis. These metabolic alterations could potentially be exploited as novel treatment targets for TNBC.

Method and apparatus for generating highly luminous flame

Energy Technology Data Exchange (ETDEWEB)

Gitman, G.M.

1992-05-12

A combustion process and apparatus are provided for generating a variable high temperature, highly luminous flame with low NOx emission by burning gaseous and liquid materials with oxygen and air. More particularly, the invention provides a process in which there is initial control of fuel, oxygen, and air flows and the delivery of the oxidizers to a burner as two oxidizing gases having different oxygen concentrations (for example, pure oxygen and air, or oxygen and oxygen-enriched air). A first oxidizing gas containing a high oxygen concentration is injected as a stream into the central zone of a combustion tunnel or chamber, and part of the fuel (preferably the major part) is injected into the central pyrolysis zone to mix with the first oxidizing gas to create a highly luminous high-temperature flame core containing microparticles of carbon of the proper size for maximum luminosity and high temperature, and a relatively small amount of hydrocarbon radicals. In addition, part of the fuel (preferably the minor part) is injected in a plurality of streams about the flame core to mix with a second oxidizing gas (containing a lower oxygen concentration than the first oxidizing gas) and injecting the second oxidizing mixture about the flame core and the minor fuel flow to mix with the minor fuel flow. This creates a plurality of fuel-lean (oxygen-rich) flames which are directed toward the luminous flame core to form a final flame pattern having high temperature, high luminosity, and low NOx content. 6 figs.

Effect of luminance contrast on BOLD-fMRI response in deaf and normal occipital visual cortex

International Nuclear Information System (INIS)

Xue Yanping; Zhai Renyou; Jiang Tao; Cui Yong; Zhou Tiangang; Rao Hengyi; Zhuo Yan

2002-01-01

Objective: To examine the effect of luminance contrast stimulus by using blood oxygenation level dependent functional magnetic resonance imaging (BOLD-fMRI) within deaf occipital visual cortex, and to compare the distribution, extent, and intensity of activated areas between deaf subjects and normal hearing subjects. Methods: Twelve deaf subjects (average age 16.5) and 15 normal hearing subjects (average age 23.7) were stimulated by 4 kinds of luminance contrast (0.7, 2.2, 50.0, 180.0 lm). The fMRI data were collected on GE 1.5 T Signa Horizon LX MRI system and analyzed by AFNI to generate the activation map. Results: Responding to all 4 kinds of stimulus luminance contrast, all deaf and normal subjects showed significant activations in occipital visual cortex. For both deaf and normal subjects, the number of activated pixels increased significantly with increasing luminance contrast (F normal = 4.27, P deaf = 6.41, P 0.05). The local mean activation level for all activated pixels remained constant with increasing luminance contrast. However, there was an increase in the mean activation level for those activated pixels common to all trials as the stimulus luminance contrast was increased, but no significant difference was found within them (F normal = 0.79, P > 0.05; F deaf = 1.6, P > 0.05). Conclusion: The effect of luminance contrast on occipital visual cortex of deaf is similar to but somewhat higher than that of normal hearing subjects. In addition, it also proved that fMRI is a feasible method in the study of the deaf visual cortex

Relation between acid back-diffusion and luminal surface hydrophobicity in canine gastric mucosa: Effects of salicylate and prostaglandin

International Nuclear Information System (INIS)

Goddard, P.J.

1989-01-01

The stomach is thought to be protected from luminal acid by a gastric mucosal barrier that restricts the diffusion of acid into tissue. This study tested the hypothesis that the hydrophobic luminal surface of canine gastric mucosa incubated in Ussing chambers, impedes the back-diffusion of luminal acid into the tissue. Isolated sheets of mucosa were treated with cimetidine to inhibit spontaneous acid secretion, and incubated under conditions that prevented significant secretion of luminal bicarbonate. By measuring acid loss from the luminal compartment using the pH-stat technique, acid back-diffusion was continuously monitored; potential difference (PD) was measured as an index of tissue viability. Tissue luminal surface hydrophobicity was estimated by contact angle analysis at the end of each experiment. Addition of 16,16-dimethyl prostaglandin E 2 to the nutrient compartment enhanced luminal surface hydrophobicity, but did not reduce acid back-diffusion in tissues that maintained a constant PD. 10 mM salicylate at pH 4.00 in the luminal compartment reduced surface hydrophobicity, but this decrease did not occur if 1 ug/ml prostaglandin was present in the nutrient solution. Despite possessing relatively hydrophilic and relatively hydrophobic surface properties, respectively, acid back-diffusion in the absence of salicylate was not significantly different between these two groups. Neither group maintained a PD after incubation with salicylate. Lastly, radiolabeled salicylate was used to calculate the free (non-salicylate associated) acid loss in tissues incubated with salicylate and/or prostaglandin. No significant correlation was found between free acid back-diffusion and luminal surface hydrophobicity. These data do not support the hypothesis that acid back-diffusion in impeded by the hydrophobic surface presented by isolated canine gastric mucosa

Luminally Acting Agents for Constipation Treatment: A Review Based on Literatures and Patents

Directory of Open Access Journals (Sweden)

Hong Yang

2017-06-01

Full Text Available Constipation is one of the most frequently reported gastrointestinal (GI disorders that negatively impacts quality of life and is associated with a significant economic burden to the patients and society. Traditional treatments including lifestyle modification and laxatives are often ineffective in the more severe forms of constipation and over the long term. New medications targeting at intestinal chloride channels and colonic serotonin receptors have been demonstrated effective in recent years. Emerging agents focusing on improving intestinal secretion and/or colonic motility have been shown effective in animal models and even in clinical trials. Recognization of the role of cystic fibrosis transmembrane regulator (CFTR and calcium-activated chloride channels (CaCCs in intestine fluid secretion and motility modulation makes CFTR and CaCCs promising molecule targets for anti-constipation therapy. Although there are multiple choices for constipation treatment, there is still a recognized need for new medications in anti-constipation therapy. The present review covers the discovery of luminally acting agents for constipation treatment described in both patents (2011–present and scientific literatures.

Therapeutically targeting mitochondrial redox signalling alleviates endothelial dysfunction in preeclampsia.

Science.gov (United States)

McCarthy, Cathal; Kenny, Louise C

2016-09-08

Aberrant placentation generating placental oxidative stress is proposed to play a critical role in the pathophysiology of preeclampsia. Unfortunately, therapeutic trials of antioxidants have been uniformly disappointing. There is provisional evidence implicating mitochondrial dysfunction as a source of oxidative stress in preeclampsia. Here we provide evidence that mitochondrial reactive oxygen species mediates endothelial dysfunction and establish that directly targeting mitochondrial scavenging may provide a protective role. Human umbilical vein endothelial cells exposed to 3% plasma from women with pregnancies complicated by preeclampsia resulted in a significant decrease in mitochondrial function with a subsequent significant increase in mitochondrial superoxide generation compared to cells exposed to plasma from women with uncomplicated pregnancies. Real-time PCR analysis showed increased expression of inflammatory markers TNF-α, TLR-9 and ICAM-1 respectively in endothelial cells treated with preeclampsia plasma. MitoTempo is a mitochondrial-targeted antioxidant, pre-treatment of cells with MitoTempo protected against hydrogen peroxide-induced cell death. Furthermore MitoTempo significantly reduced mitochondrial superoxide production in cells exposed to preeclampsia plasma by normalising mitochondrial metabolism. MitoTempo significantly altered the inflammatory profile of plasma treated cells. These novel data support a functional role for mitochondrial redox signaling in modulating the pathogenesis of preeclampsia and identifies mitochondrial-targeted antioxidants as potential therapeutic candidates.

High-Risk Premenopausal Luminal A Breast Cancer Patients Derive no Benefit from Adjuvant Cyclophosphamide-based Chemotherapy

DEFF Research Database (Denmark)

Nielsen, Torsten O; Jensen, Maj-Brit; Burugu, Samantha

2017-01-01

Purpose: Luminal A breast cancers have better prognosis than other molecular subtypes. Luminal A cancers may also be insensitive to adjuvant chemotherapy, although there is little high-level evidence to confirm this concept. The primary hypothesis in this formal prospective-retrospective analysis...... was to assess interaction between subtype (Luminal A vs. other) and treatment (chemotherapy vs. not) for the primary endpoint (10-year invasive disease-free survival) of a breast cancer trial randomizing women to adjuvant chemotherapy, analyzed in multivariate Cox proportional hazards models using the Wald...... interval (CI), 0.53-2.14; P = 0.86], whereas patients with non-luminal A subtypes did (HR, 0.50; 95% CI, 0.38-0.66; P breast cancers did not benefit from adjuvant...

Environmental radioactive monitoring, evaluation and protection in luminous workshops of a factory

International Nuclear Information System (INIS)

Dai Hanbin; Xiang Ming; Tan Jianzu

2009-01-01

Fluorescent technique is often used to display instrumental indicator in the dark environment. Luminous workshops of a factory smear and depict the glassware by means of fluorescent power with adulterated radioactive matter. Because of adulterated radioactive matters such as 226 Ra, 40 K emit alpha-ray,beta-ray and gamma-ray, while they decay spontaneously, and high dose or cumulative radiation can damage human body in different degrees. Therefore, any radioactive damage to human body caused by over-safety dose should be prevented strictly during the working. To ensure health and safety of working staff in luminous workshop and the public, it is necessary to regularly have radioactive monitoring and evaluation to luminous workshop and its surrounding environment. Through the environment radioactive monitoring, the authors analyze its environmental radioactive level,and try to find out the possible problems so as to propose some protective measures for personal health. (authors)

Automatic detection of the unknown number point targets in FMICW radar signals

Czech Academy of Sciences Publication Activity Database

Rejfek, L.; Mošna, Zbyšek; Beran, L.; Fišer, O.; Dobrovolný, M.

2017-01-01

Roč. 4, č. 11 (2017), s. 116-120 ISSN 2313-626X R&D Projects: GA ČR(CZ) GA15-24688S Institutional support: RVO:68378289 Keywords : FMICW radar * 2D FFT * signal filtration * taraget detection * target parameter estimation Subject RIV: DG - Athmosphere Sciences, Meteorology OBOR OECD: Meteorology and atmospheric sciences http://science-gate.com/IJAAS/Articles/2017-4-11/18%202017-4-11-pp.116-120.pdf

3D-segmentation of the 18F-choline PET signal for target volume definition in radiation therapy of the prostate.

Science.gov (United States)

Ciernik, I Frank; Brown, Derek W; Schmid, Daniel; Hany, Thomas; Egli, Peter; Davis, J Bernard

2007-02-01

Volumetric assessment of PET signals becomes increasingly relevant for radiotherapy (RT) planning. Here, we investigate the utility of 18F-choline PET signals to serve as a structure for semi-automatic segmentation for forward treatment planning of prostate cancer. 18F-choline PET and CT scans of ten patients with histologically proven prostate cancer without extracapsular growth were acquired using a combined PET/CT scanner. Target volumes were manually delineated on CT images using standard software. Volumes were also obtained from 18F-choline PET images using an asymmetrical segmentation algorithm. PTVs were derived from CT 18F-choline PET based clinical target volumes (CTVs) by automatic expansion and comparative planning was performed. As a read-out for dose given to non-target structures, dose to the rectal wall was assessed. Planning target volumes (PTVs) derived from CT and 18F-choline PET yielded comparable results. Optimal matching of CT and 18F-choline PET derived volumes in the lateral and cranial-caudal directions was obtained using a background-subtracted signal thresholds of 23.0+/-2.6%. In antero-posterior direction, where adaptation compensating for rectal signal overflow was required, optimal matching was achieved with a threshold of 49.5+/-4.6%. 3D-conformal planning with CT or 18F-choline PET resulted in comparable doses to the rectal wall. Choline PET signals of the prostate provide adequate spatial information amendable to standardized asymmetrical region growing algorithms for PET-based target volume definition for external beam RT.

Luminal flow amplifies stent-based drug deposition in arterial bifurcations.

Directory of Open Access Journals (Sweden)

Vijaya B Kolachalama

2009-12-01

Full Text Available Treatment of arterial bifurcation lesions using drug-eluting stents (DES is now common clinical practice and yet the mechanisms governing drug distribution in these complex morphologies are incompletely understood. It is still not evident how to efficiently determine the efficacy of local drug delivery and quantify zones of excessive drug that are harbingers of vascular toxicity and thrombosis, and areas of depletion that are associated with tissue overgrowth and luminal re-narrowing.We constructed two-phase computational models of stent-deployed arterial bifurcations simulating blood flow and drug transport to investigate the factors modulating drug distribution when the main-branch (MB was treated using a DES. Simulations predicted extensive flow-mediated drug delivery in bifurcated vascular beds where the drug distribution patterns are heterogeneous and sensitive to relative stent position and luminal flow. A single DES in the MB coupled with large retrograde luminal flow on the lateral wall of the side-branch (SB can provide drug deposition on the SB lumen-wall interface, except when the MB stent is downstream of the SB flow divider. In an even more dramatic fashion, the presence of the SB affects drug distribution in the stented MB. Here fluid mechanic effects play an even greater role than in the SB especially when the DES is across and downstream to the flow divider and in a manner dependent upon the Reynolds number.The flow effects on drug deposition and subsequent uptake from endovascular DES are amplified in bifurcation lesions. When only one branch is stented, a complex interplay occurs - drug deposition in the stented MB is altered by the flow divider imposed by the SB and in the SB by the presence of a DES in the MB. The use of DES in arterial bifurcations requires a complex calculus that balances vascular and stent geometry as well as luminal flow.

Virulence of luminous vibrios to Artemia franciscana nauplii.

Science.gov (United States)

Soto-Rodriguez, S A; Roque, A; Lizarraga-Partida, M L; Guerra-Flores, A L; Gomez-Gill, B

2003-02-27

From healthy and diseased penaeid shrimp from Asia and the Americas, 25 luminous and 2 non-luminous bacterial strains were isolated, and 14 were phenotypically identified as Vibrio harveyi; 9 isolates produced significant mortalities (45 to 80%) in Artemia franciscana nauplii at inoculation densities of 10(5) to 10(6) CFU ml(-1) compared to the controls (unchallenged nauplii). The maximum number of bacteria ingested (bioencapsulated) by the Artemia nauplii varied from less than 10 to 10(3) CFU nauplius(-1) and no significant relationship was observed between the density of bacteria inoculated, the amount of bacteria ingested, and naupliar mortality. Significant correlations were obtained between naupliar mortality and production of proteases, phospholipases or siderophores, but not between mortality and lipase production, gelatinase production, hydrophobicity or hemolytic activity. The results suggest that virulence of the strains tested was more related to the production of particular exoenzymes than to the measured colonization factors.

Targeting NRF2 signaling for cancer chemoprevention

International Nuclear Information System (INIS)

Kwak, Mi-Kyoung; Kensler, Thomas W.

2010-01-01

Modulation of the metabolism and disposition of carcinogens through induction of cytoprotective enzymes is one of several promising strategies to prevent cancer. Chemopreventive efficacies of inducers such as dithiolethiones and sulforaphane have been extensively studied in animals as well as in humans. The KEAP1-NRF2 system is a key, but not unilateral, molecular target for these chemopreventive agents. The transcription factor NRF2 (NF-E2-related factor 2) is a master regulator of the expression of a subset of genes, which produce proteins responsible for the detoxication of electrophiles and reactive oxygen species as well as the removal or repair of some of their damage products. It is believed that chemopreventive enzyme inducers affect the interaction between KEAP1 and NRF2 through either mediating conformational changes of the KEAP1 protein or activating phosphorylation cascades targeting the KEAP1-NRF2 complex. These events in turn affect NRF2 stability and trafficking. Recent advances elucidating the underlying structural biology of KEAP1-NRF2 signaling and identification of the gene clusters under the transcriptional control of NRF2 are facilitating understanding of the potential pleiotropic effects of NRF2 activators and discovery of novel classes of potent chemopreventive agents such as the triterpenoids. Although there is appropriately a concern regarding a deleterious role of the KEAP1-NRF2 system in cancer cell biology, especially as the pathway affects cell survival and drug resistance, the development and the use of NRF2 activators as chemopreventive agents still holds a great promise for protection of normal cells from a diversity of environmental stresses that contribute to the burden of cancer and other chronic, degenerative diseases.

Targeting the phosphatidylinositol 3-kinase/Akt/mechanistic target of rapamycin signaling pathway in B-lineage acute lymphoblastic leukemia: An update.

Science.gov (United States)

Simioni, Carolina; Martelli, Alberto M; Zauli, Giorgio; Vitale, Marco; McCubrey, James A; Capitani, Silvano; Neri, Luca M

2018-04-18

Despite considerable progress in treatment protocols, B-lineage acute lymphoblastic leukemia (B-ALL) displays a poor prognosis in about 15-20% of pediatric cases and about 60% of adult patients. In addition, life-long irreversible late effects from chemo- and radiation therapy, including secondary malignancies, are a growing problem for leukemia survivors. Targeted therapy holds promising perspectives for cancer treatment as it may be more effective and have fewer side effects than conventional therapies. The phosphatidylinositol 3-phosphate kinase (PI3K)/Akt/mechanistic target of rapamycin (mTOR) signaling pathway is a key regulatory cascade which controls proliferation, survival and drug-resistance of cancer cells, and it is frequently upregulated in the different subtypes of B-ALL, where it plays important roles in the pathophysiology, maintenance and progression of the disease. Moreover, activation of this signaling cascade portends a poorer prognosis in both pediatric and adult B-ALL patients. Promising preclinical data on PI3K/Akt/mTOR inhibitors have documented their anticancer activity in B-ALL and some of these novel drugs have entered clinical trials as they could lead to a longer event-free survival and reduce therapy-associated toxicity for patients with B-ALL. This review highlights the current status of PI3K/Akt/mTOR inhibitors in B-ALL, with an emphasis on emerging evidence of the superior efficacy of synergistic combinations involving the use of traditional chemotherapeutics or other novel, targeted agents. © 2018 Wiley Periodicals, Inc.

Series-nonuniform rational B-spline signal feedback: From chaos to any embedded periodic orbit or target point

Energy Technology Data Exchange (ETDEWEB)

Shao, Chenxi, E-mail: cxshao@ustc.edu.cn; Xue, Yong; Fang, Fang; Bai, Fangzhou [Department of Computer Science and Technology, University of Science and Technology of China, Hefei 230027 (China); Yin, Peifeng [Department of Computer Science and Engineering, Pennsylvania State University, State College, Pennsylvania 16801 (United States); Wang, Binghong [Department of Modern Physics, University of Science and Technology of China, Hefei 230026 (China)

2015-07-15

The self-controlling feedback control method requires an external periodic oscillator with special design, which is technically challenging. This paper proposes a chaos control method based on time series non-uniform rational B-splines (SNURBS for short) signal feedback. It first builds the chaos phase diagram or chaotic attractor with the sampled chaotic time series and any target orbit can then be explicitly chosen according to the actual demand. Second, we use the discrete timing sequence selected from the specific target orbit to build the corresponding external SNURBS chaos periodic signal, whose difference from the system current output is used as the feedback control signal. Finally, by properly adjusting the feedback weight, we can quickly lead the system to an expected status. We demonstrate both the effectiveness and efficiency of our method by applying it to two classic chaotic systems, i.e., the Van der Pol oscillator and the Lorenz chaotic system. Further, our experimental results show that compared with delayed feedback control, our method takes less time to obtain the target point or periodic orbit (from the starting point) and that its parameters can be fine-tuned more easily.

Series-nonuniform rational B-spline signal feedback: From chaos to any embedded periodic orbit or target point.

Science.gov (United States)

Shao, Chenxi; Xue, Yong; Fang, Fang; Bai, Fangzhou; Yin, Peifeng; Wang, Binghong

2015-07-01

The self-controlling feedback control method requires an external periodic oscillator with special design, which is technically challenging. This paper proposes a chaos control method based on time series non-uniform rational B-splines (SNURBS for short) signal feedback. It first builds the chaos phase diagram or chaotic attractor with the sampled chaotic time series and any target orbit can then be explicitly chosen according to the actual demand. Second, we use the discrete timing sequence selected from the specific target orbit to build the corresponding external SNURBS chaos periodic signal, whose difference from the system current output is used as the feedback control signal. Finally, by properly adjusting the feedback weight, we can quickly lead the system to an expected status. We demonstrate both the effectiveness and efficiency of our method by applying it to two classic chaotic systems, i.e., the Van der Pol oscillator and the Lorenz chaotic system. Further, our experimental results show that compared with delayed feedback control, our method takes less time to obtain the target point or periodic orbit (from the starting point) and that its parameters can be fine-tuned more easily.

miR-130b targets NKD2 and regulates the Wnt signaling to promote proliferation and inhibit apoptosis in osteosarcoma cells

Energy Technology Data Exchange (ETDEWEB)

Li, Zhi [Department of Human Anatomy and Histoembryology, College of Basic Medical Sciences, Jilin University (China); Li, Youjun, E-mail: liyoujunn@126.com [Department of Human Anatomy and Histoembryology, College of Basic Medical Sciences, Jilin University (China); Wang, Nan; Yang, Lifeng; Zhao, Wei; Zeng, Xiandong [Central Hospital Affiliated to Shenyang Medical College (China)

2016-03-18

miR-130b was significantly up-regulated in osteosarcoma (OS) cells. Naked cuticle homolog 2 (NKD2) inhibited tumor growth and metastasis in OS by suppressing Wnt signaling. We used three miRNA target analysis tools to identify potential targets of miR-130b, and found that NKD2 is a potential target of miR-130b. Based on these findings, we hypothesize that miR-130b might target NKD2 and regulate the Wnt signaling to promote OS growth. We detected the expression of miR-130b and NKD2 mRNA and protein by quantitative Real-Time PCR (qRT-PCR) and western blot assays, respectively, and found up-regulation of miR-130b and down-regulation of NKD2 mRNA and protein exist in OS cell lines. MTT and flow cytometry assays showed that miR-130b inhibitors inhibit proliferation and promote apoptosis in OS cells. Furthermore, we showed that NKD2 is a direct target of miR-130b, and miR-130b regulated proliferation and apoptosis of OS cells by targeting NKD2. We further investigated whether miR-130b and NKD2 regulate OS cell proliferation and apoptosis by inhibiting Wnt signaling, and the results confirmed our speculation that miR-130b targets NKD2 and regulates the Wnt signaling to promote proliferation and inhibit apoptosis of OS cells. These findings will offer new clues for OS development and progression, and novel potential therapeutic targets for OS. - Highlights: • miR-130b is up-regulated and NKD2 is down-regulated in osteosarcoma cell lines. • Down-regulation of miR-130b inhibits proliferation of osteosarcoma cells. • Down-regulation of miR-130b promotes apoptosis of osteosarcoma cells. • miR-130b directly targets NKD2. • NKD2 regulates OS cell proliferation and apoptosis by inhibiting the Wnt signaling.

miR-130b targets NKD2 and regulates the Wnt signaling to promote proliferation and inhibit apoptosis in osteosarcoma cells

International Nuclear Information System (INIS)

Li, Zhi; Li, Youjun; Wang, Nan; Yang, Lifeng; Zhao, Wei; Zeng, Xiandong

2016-01-01

miR-130b was significantly up-regulated in osteosarcoma (OS) cells. Naked cuticle homolog 2 (NKD2) inhibited tumor growth and metastasis in OS by suppressing Wnt signaling. We used three miRNA target analysis tools to identify potential targets of miR-130b, and found that NKD2 is a potential target of miR-130b. Based on these findings, we hypothesize that miR-130b might target NKD2 and regulate the Wnt signaling to promote OS growth. We detected the expression of miR-130b and NKD2 mRNA and protein by quantitative Real-Time PCR (qRT-PCR) and western blot assays, respectively, and found up-regulation of miR-130b and down-regulation of NKD2 mRNA and protein exist in OS cell lines. MTT and flow cytometry assays showed that miR-130b inhibitors inhibit proliferation and promote apoptosis in OS cells. Furthermore, we showed that NKD2 is a direct target of miR-130b, and miR-130b regulated proliferation and apoptosis of OS cells by targeting NKD2. We further investigated whether miR-130b and NKD2 regulate OS cell proliferation and apoptosis by inhibiting Wnt signaling, and the results confirmed our speculation that miR-130b targets NKD2 and regulates the Wnt signaling to promote proliferation and inhibit apoptosis of OS cells. These findings will offer new clues for OS development and progression, and novel potential therapeutic targets for OS. - Highlights: • miR-130b is up-regulated and NKD2 is down-regulated in osteosarcoma cell lines. • Down-regulation of miR-130b inhibits proliferation of osteosarcoma cells. • Down-regulation of miR-130b promotes apoptosis of osteosarcoma cells. • miR-130b directly targets NKD2. • NKD2 regulates OS cell proliferation and apoptosis by inhibiting the Wnt signaling.

Contribution of a luminance-dependent S-cone mechanism to non-assimilative color spreading in the watercolor configuration

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Eiji eKimura

2014-12-01

Full Text Available In the watercolor configuration composed of wavy double contours, both assimilative and non-assimilative color spreading have been demonstrated depending on the luminance conditions of the inner and outer contours (IC and OC, respectively. This study investigated how the induced color in the watercolor configuration was modulated by combinations of the IC and the OC color, particularly addressing non-assimilative color spreading. In two experiments, the IC color was fixed to a certain color and combined with various colors selected from a hue circle centered at the background white color. Color spreading was quantified with a chromatic cancellation technique. Results showed that both the magnitude and the apparent hue of the color spreading were largely changed with the luminance condition. When the IC contrast (Weber contrast of the IC to the background luminance was smaller in size than the OC contrast (higher IC luminance condition, the color spreading was assimilative. When the luminance condition was reversed and the IC contrast was greater than the OC contrast (lower IC luminance condition, the color spreading was non-assimilative and yellowish. When the color spreading was analyzed in terms of cone-opponent excitations, the results were consistent with the interpretation that the color spreading is explainable by a combination of chromatic diffusion from the IC and chromatically opponent induction from the OC. The color spreading in the higher IC luminance condition mainly reflected the chromatic diffusion by both (L–M and S cone-opponent mechanisms. The non-assimilative color spreading in the lower IC luminance condition mostly reflected S-cone mediated opponent induction and the contribution of -S inducing mechanisms was differentially large. These findings provided several constraints on possible visual mechanisms underlying the watercolor effect.

Contribution of a luminance-dependent S-cone mechanism to non-assimilative color spreading in the watercolor configuration.

Science.gov (United States)

Kimura, Eiji; Kuroki, Mikako

2014-01-01

In the watercolor configuration composed of wavy double contours, both assimilative and non-assimilative color spreading have been demonstrated depending on the luminance conditions of the inner and outer contours (IC and OC, respectively). This study investigated how the induced color in the watercolor configuration was modulated by combinations of the IC and the OC color, particularly addressing non-assimilative color spreading. In two experiments, the IC color was fixed to a certain color and combined with various colors selected from a hue circle centered at the background white color. Color spreading was quantified with a chromatic cancelation technique. Results showed that both the magnitude and the apparent hue of the color spreading were largely changed with the luminance condition. When the IC contrast (Weber contrast of the IC to the background luminance) was smaller in size than the OC contrast (higher IC luminance condition), the color spreading was assimilative. When the luminance condition was reversed and the IC contrast was greater than the OC contrast (lower IC luminance condition), the color spreading was non-assimilative and yellowish. When the color spreading was analyzed in terms of cone-opponent excitations, the results were consistent with the interpretation that the color spreading is explainable by a combination of chromatic diffusion from the IC and chromatically opponent induction from the OC. The color spreading in the higher IC luminance condition mainly reflected the chromatic diffusion by both (L-M) and S cone-opponent mechanisms. The non-assimilative color spreading in the lower IC luminance condition mostly reflected S-cone mediated opponent induction and the contribution of -S inducing mechanisms was differentially large. These findings provided several constraints on possible visual mechanisms underlying the watercolor effect.

Immunohistochemical localisation of keratin and luminal epithelial antigen in myoepithelial and luminal epithelial cells of human mammary and salivary gland tumours.

Science.gov (United States)

Nathrath, W B; Wilson, P D; Trejdosiewicz, L K

1982-01-01

Rabbit antisera to human 40-63 000 MW epidermal keratin, one batch with restricted distribution of reactivity from an initial (aK1) and one with "broad spectrum" distribution of reactivity from a late bleeding (aK), and to "luminal epithelial antigen" (aLEA) were applied to formalin fixed paraffin embedded sections of human normal and neoplastic mammary and salivary glands using an indirect immunoperoxidase method. aK1 reacted with myoepithelial cells, aLEA with luminal epithelial cells and aK with both cell types in normal mammary and salivary gland. In breast carcinomas the majority of intraluminal and infiltrating carcinoma cells reacted with aLEA but not with aK1 which reacted only with surrounding myoepithelial cells. aK reacted with both myoepithelial cells and with intraluminal and infiltrating tumour cells. In the salivary gland adenomas the majority of cells reacted with aK, and those cells arranged in a tubular fashion reacted with aLEA.

Luminal DMSO: Effects on Detrusor and Urothelial/Lamina Propria Function

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Katrina J. Smith

2014-01-01

Full Text Available DMSO is used as a treatment for interstitial cystitis and this study examined the effects of luminal DMSO treatment on bladder function and histology. Porcine bladder was incubated without (controls or with DMSO (50% applied to the luminal surface and the release of ATP, acetylcholine, and LDH assessed during incubation and in tissues strips after DMSO incubation. Luminally applied DMSO caused ATP, Ach, and LDH release from the urothelial surface during treatment, with loss of urothelial layers also evident histologically. In strips of urothelium/lamina propria from DMSO pretreated bladders the release of both ATP and Ach was depressed, while contractile responses to carbachol were enhanced. Detrusor muscle contractile responses to carbachol were not affected by DMSO pretreatment, but neurogenic responses to electrical field stimulation were enhanced. The presence of an intact urothelium/lamina propria inhibited detrusor contraction to carbachol by 53% and this inhibition was significantly reduced in DMSO pretreated tissues. Detection of LDH in the treatment medium suggests that DMSO permeabilised urothelial membranes causing leakage of cytosolic contents including ATP and Ach rather than enhancing release of these mediators. The increase in contractile response and high levels of ATP are consistent with initial flare up in IC/PBS symptoms after DMSO treatment.

Homogeneous electrochemical aptamer-based ATP assay with signal amplification by exonuclease III assisted target recycling.

Science.gov (United States)

Liu, Shufeng; Wang, Ying; Zhang, Chengxin; Lin, Ying; Li, Feng

2013-03-21

A novel and homogeneous electrochemical aptamer-based adenosine triphosphate (ATP) assay was demonstrated with signal amplification by exonuclease III-assisted target recycling. A superior detection limit of 1 nM toward ATP with an excellent selectivity could be achieved.

Target-assistant Zn2+-dependent DNAzyme for signal-on electrochemiluminescent biosensing

International Nuclear Information System (INIS)

Huang, Yin; Lei, Jianping; Cheng, Yan; Ju, Huangxian

2015-01-01

Highlights: • The sensing strategy is based on cleavage reaction of target-assistant Zn 2+ -dependent DNAzyme. • A dual quenching mechanism of ECL is identified. • A sensitive and selective ECL sensor is constructed for detection of ATP. • The biosensor can detect ATP in serum samples with good accuracy. - Abstract: A signal-on electrochemiluminescent (ECL) approach for ultrasensitive ATP detection was developed using target-assistant Zn 2+ -dependent DNAzyme via a dual quenching pathway between quantum dots (QDs) and Au nanoclusters (Au NCs). The facile ECL biosensor was constructed by covalent assembly of Au NCs-labeled hairpin DNA on QDs modified glassy carbon electrode. A dual quenching ECL mechanism was identified to be via resonance energy transfer between QDs and Au NCs and electrocatalytic reduction of coreactant oxygen by Au NCs. With the assistance of two help DNAs, the G-quadruplex structure of ATP aptamer was formed, and thus narrowed the two fragments of Zn 2+ -dependent DNAzyme. In the presence of Zn 2+ , Zn 2+ -dependent DNAzyme can be generated in situ on the biosensor's surface. The as-prepared DNAzyme can cleave the substrate strand, and release the Au NCs from the electrode, resulting in the signal-on ECL state. This biosensor showed good analytical performance with 4 orders magnitude linear range, excellent specificity, and acceptable stability. The biosensor had been applied in detection of ATP in real serum sample and provided significant potential application in clinical analysis

Hsa-miR-11181 regulates Wnt signaling pathway through targeting of APC2 transcripts in SW480 cell line.

Science.gov (United States)

Dokanehiifard, Sadat; Soltani, Bahram M

2018-01-30

Wnt signaling plays important roles in differentiation, morphogenesis and development. This signaling pathway is highly regulated at all levels and microRNAs are small noncoding RNAs regulating Wnt signaling. Here, we intended to investigate hsa-miR-11181 (a novel miRNA located in TrkC gene) effect on Wnt signaling pathway in SW480 cell line. TOP/FOP flash assay indicated up-regulation of Wnt signaling, following the overexpression of hsa-miR-11181, verified through RT-qPCR. Bioinformatics analysis predicted APC1, APC2 and Axin1 might be targeted by hsa-miR-11181. Then, RT-qPCR analysis indicated that APC2 and Axin1 have been significantly down-regulated following the hsa-miR-11181 overexpression. However dual luciferase assay analysis supported only APC2 3'-UTR is directly targeted by this miRNA. Then, treatment of SW480 cells with Wnt-inhibitory small molecules supported the effect of hsa-miR-11181 at the inhibitory complex level containing APC2 protein. Consistently, viability of SW480 cells overexpressing hsa-miR-11181 was significantly elevated, measured through MTT assay. Overall, these results suggest that hsa-miR-11181 may play a crucial role in Wnt signaling regulation and confirmed that APC2 3'-UTR is targeted by hsa-miR-11181 and propose the presence of its recognition sites in the promoter or coding regions of Axin1 gene. Copyright © 2017. Published by Elsevier B.V.

Rapamycin and Glucose-Target of Rapamycin (TOR) Protein Signaling in Plants*

Science.gov (United States)

Xiong, Yan; Sheen, Jen

2012-01-01

Target of rapamycin (TOR) kinase is an evolutionarily conserved master regulator that integrates energy, nutrients, growth factors, and stress signals to promote survival and growth in all eukaryotes. The reported land plant resistance to rapamycin and the embryo lethality of the Arabidopsis tor mutants have hindered functional dissection of TOR signaling in plants. We developed sensitive cellular and seedling assays to monitor endogenous Arabidopsis TOR activity based on its conserved S6 kinase (S6K) phosphorylation. Surprisingly, rapamycin effectively inhibits Arabidopsis TOR-S6K1 signaling and retards glucose-mediated root and leaf growth, mimicking estradiol-inducible tor mutants. Rapamycin inhibition is relieved in transgenic plants deficient in Arabidopsis FK506-binding protein 12 (FKP12), whereas FKP12 overexpression dramatically enhances rapamycin sensitivity. The role of Arabidopsis FKP12 is highly specific as overexpression of seven closely related FKP proteins fails to increase rapamycin sensitivity. Rapamycin exerts TOR inhibition by inducing direct interaction between the TOR-FRB (FKP-rapamycin binding) domain and FKP12 in plant cells. We suggest that variable endogenous FKP12 protein levels may underlie the molecular explanation for longstanding enigmatic observations on inconsistent rapamycin resistance in plants and in various mammalian cell lines or diverse animal cell types. Integrative analyses with rapamycin and conditional tor and fkp12 mutants also reveal a central role of glucose-TOR signaling in root hair formation. Our studies demonstrate the power of chemical genetic approaches in the discovery of previously unknown and pivotal functions of glucose-TOR signaling in governing the growth of cotyledons, true leaves, petioles, and primary and secondary roots and root hairs. PMID:22134914

SURVEY OF THE ENTOMOFAUNA THROUGH LUMINOUS TRAP

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V. R. Andrade Neto

2014-09-01

Full Text Available The demand for forest-based raw materials for energy, construction, paper pulp and the pressure to comply with legal requirements concerning environmental legislation, for example, the replacement of the permanent preservation area, legal reserve and recovery of degraded area, leads to encourage the production of healthy seedlings in a health status to do not compromise their future production. The present study aimed to survey the entomofauna population using the “Luiz de Queiroz” model of luminous trap, with white and red fluorescent lamps. The experiment was conducted at the nursery “Flora Sinop” in Sinop – MT. The survey was conducted weekly between the months of April to July 2010, totaling 4 months sand, 32 samples collected. The orders Hemiptera and Coleoptera showed the highest number of individuals captured, either in attraction with white or red light. It was captured 10.089 individuals, 9.339 collected under the influence of white light, representing 92,56%, and 750 with red light, only 7,44% of the total. The white light luminous trap possessed greater efficiency in the attraction of insects when compared with the red light trap.

Different responses of spontaneous and stimulus-related alpha activity to ambient luminance changes.

Science.gov (United States)

Benedetto, Alessandro; Lozano-Soldevilla, Diego; VanRullen, Rufin

2017-12-04

Alpha oscillations are particularly important in determining our percepts and have been implicated in fundamental brain functions. Oscillatory activity can be spontaneous or stimulus-related. Furthermore, stimulus-related responses can be phase- or non-phase-locked to the stimulus. Non-phase-locked (induced) activity can be identified as the average amplitude changes in response to a stimulation, while phase-locked activity can be measured via reverse-correlation techniques (echo function). However, the mechanisms and the functional roles of these oscillations are far from clear. Here, we investigated the effect of ambient luminance changes, known to dramatically modulate neural oscillations, on spontaneous and stimulus-related alpha. We investigated the effect of ambient luminance on EEG alpha during spontaneous human brain activity at rest (experiment 1) and during visual stimulation (experiment 2). Results show that spontaneous alpha amplitude increased by decreasing ambient luminance, while alpha frequency remained unaffected. In the second experiment, we found that under low-luminance viewing, the stimulus-related alpha amplitude was lower, and its frequency was slightly faster. These effects were evident in the phase-locked part of the alpha response (echo function), but weaker or absent in the induced (non-phase-locked) alpha responses. Finally, we explored the possible behavioural correlates of these modulations in a monocular critical flicker frequency task (experiment 3), finding that dark adaptation in the left eye decreased the temporal threshold of the right eye. Overall, we found that ambient luminance changes impact differently on spontaneous and stimulus-related alpha expression. We suggest that stimulus-related alpha activity is crucial in determining human temporal segmentation abilities. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

High luminous flux from single crystal phosphor-converted laser-based white lighting system

KAUST Repository

Cantore, Michael

2015-12-14

The efficiency droop of light emitting diodes (LEDs) with increasing current density limits the amount of light emitted per wafer area. Since low current densities are required for high efficiency operation, many LED die are needed for high power white light illumination systems. In contrast, the carrier density of laser diodes (LDs) clamps at threshold, so the efficiency of LDs does not droop above threshold and high efficiencies can be achieved at very high current densities. The use of a high power blue GaN-based LD coupled with a single crystal Ce-doped yttrium aluminum garnet (YAG:Ce) sample was investigated for white light illumination applications. Under CW operation, a single phosphor-converted LD (pc-LD) die produced a peak luminous efficacy of 86.7 lm/W at 1.4 A and 4.24 V and a peak luminous flux of 1100 lm at 3.0 A and 4.85 V with a luminous efficacy of 75.6 lm/W. Simulations of a pc-LD confirm that the single crystal YAG:Ce sample did not experience thermal quenching at peak LD operating efficiency. These results show that a single pc-LD die is capable of emitting enough luminous flux for use in a high power white light illumination system.

Genome-wide Analysis of RARβ Transcriptional Targets in Mouse Striatum Links Retinoic Acid Signaling with Huntington's Disease and Other Neurodegenerative Disorders.

Science.gov (United States)

Niewiadomska-Cimicka, Anna; Krzyżosiak, Agnieszka; Ye, Tao; Podleśny-Drabiniok, Anna; Dembélé, Doulaye; Dollé, Pascal; Krężel, Wojciech

2017-07-01

Retinoic acid (RA) signaling through retinoic acid receptors (RARs), known for its multiple developmental functions, emerged more recently as an important regulator of adult brain physiology. How RAR-mediated regulation is achieved is poorly known, partly due to the paucity of information on critical target genes in the brain. Also, it is not clear how reduced RA signaling may contribute to pathophysiology of diverse neuropsychiatric disorders. We report the first genome-wide analysis of RAR transcriptional targets in the brain. Using chromatin immunoprecipitation followed by high-throughput sequencing and transcriptomic analysis of RARβ-null mutant mice, we identified genomic targets of RARβ in the striatum. Characterization of RARβ transcriptional targets in the mouse striatum points to mechanisms through which RAR may control brain functions and display neuroprotective activity. Namely, our data indicate with statistical significance (FDR 0.1) a strong contribution of RARβ in controlling neurotransmission, energy metabolism, and transcription, with a particular involvement of G-protein coupled receptor (p = 5.0e -5 ), cAMP (p = 4.5e -4 ), and calcium signaling (p = 3.4e -3 ). Many identified RARβ target genes related to these pathways have been implicated in Alzheimer's, Parkinson's, and Huntington's disease (HD), raising the possibility that compromised RA signaling in the striatum may be a mechanistic link explaining the similar affective and cognitive symptoms in these diseases. The RARβ transcriptional targets were particularly enriched for transcripts affected in HD. Using the R6/2 transgenic mouse model of HD, we show that partial sequestration of RARβ in huntingtin protein aggregates may account for reduced RA signaling reported in HD.

A common signal detection model accounts for both perception and discrimination of the watercolor effect.

Science.gov (United States)

Devinck, Frédéric; Knoblauch, Kenneth

2012-03-21

Establishing the relation between perception and discrimination is a fundamental objective in psychophysics, with the goal of characterizing the neural mechanisms mediating perception. Here, we show that a procedure for estimating a perceptual scale based on a signal detection model also predicts discrimination performance. We use a recently developed procedure, Maximum Likelihood Difference Scaling (MLDS), to measure the perceptual strength of a long-range, color, filling-in phenomenon, the Watercolor Effect (WCE), as a function of the luminance ratio between the two components of its generating contour. MLDS is based on an equal-variance, gaussian, signal detection model and yields a perceptual scale with interval properties. The strength of the fill-in percept increased 10-15 times the estimate of the internal noise level for a 3-fold increase in the luminance ratio. Each observer's estimated scale predicted discrimination performance in a subsequent paired-comparison task. A common signal detection model accounts for both the appearance and discrimination data. Since signal detection theory provides a common metric for relating discrimination performance and neural response, the results have implications for comparing perceptual and neural response functions.

Alteration of SHP-1/p-STAT3 Signaling: A Potential Target for Anticancer Therapy

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Tzu-Ting Huang

2017-06-01

Full Text Available The Src homology 2 (SH2 domain-containing protein tyrosine phosphatase 1 (SHP-1, a non-receptor protein tyrosine phosphatase, has been reported as a negative regulator of phosphorylated signal transducer and activator of transcription 3 (STAT3 and linked to tumor development. In this present review, we will discuss the importance and function of SHP-1/p-STAT3 signaling in nonmalignant conditions as well as malignancies, its cross-talk with other pathways, the current clinical development and the potential role of inhibitors of this pathway in anticancer therapy and clinical relevance of SHP-1/p-STAT3 in cancers. Lastly, we will summarize and highlight work involving novel drugs/compounds targeting SHP-1/p-STAT3 signaling and combined strategies that were/are discovered in our and our colleagues’ laboratories.

Targeting sTNF/TNFR1 Signaling as a New Therapeutic Strategy

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Roman Fischer

2015-03-01

Full Text Available Deregulation of the tumor necrosis factor (TNF plays an important role in the initiation and perpetuation of chronic inflammation and has been implicated in the development of various autoimmune diseases. Accordingly, TNF-inhibitors are successfully used for the treatment of several diseases, such as rheumatoid arthritis, inflammatory bowel disease, and psoriasis. However, total inhibition of TNF can cause severe side effects such as an increased risk of inflammation and reactivation of tuberculosis. This is likely due to the different actions of the two TNF receptors. Whereas TNFR1 predominantly promotes inflammatory signaling pathways, TNFR2 mediates immune modulatory functions and promotes tissue homeostasis and regeneration. Therefore, the specific blockage of TNFR1 signaling, either by direct inhibition with TNFR1-selective antagonists or by targeting soluble TNF, which predominantly activates TNFR1, may prevent the detrimental effects associated with total TNF-inhibitors and constitute a next-generation approach to interfere with TNF.

The Research Search For The Least Beneficial Overcast Sky And Progress In Defining Its Luminance Gradation Function

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Kittler R.

2014-09-01

Full Text Available Recently illuminance levels under ISO/CIE homogeneous standard sky types were characterised in their relative terms after ISO/CIE (2004, 2003 standardised as normalised by the luminance in the zenith. Sky luminance and horizontal illuminance based on the gradation and scattering indicatrix functions, including the extreme overcast cases frequently encountered in nature, were recently determined in absolute physical units of luminance in kilocandles per meter square and of illuminance in kilolux. The historical search to find energy and visibility critical sky luminance distributions shows a progression of steps in studying the worst or critical overcast situations. That progression has enabled the determination and evaluation of interior illuminance for comparison of the merits of dual daylighting and artificial lighting under established criteria for comfortable visibility.

Fluorescence analysis of the Hansenula polymorpha peroxisomal targeting signal-1 receptor, Pex5p

NARCIS (Netherlands)

Boteva, R.; Koek, A.; Visser, N.V.; Visser, A.J.W.G.; Krieger, E.; Zlateva, T.; Veenhuis, M.; Klei, van der I.

2003-01-01

Correct sorting of newly synthesized peroxisomal matrix proteins is dependent on a peroxisomal targeting signal (PTS). So far two PTSs are known. PTS1 consists of a tripeptide that is located at the extreme C terminus of matrix proteins and is specifically recognized by the PTS1-receptor Pex5p. We

Heavy X-ray obscuration in the most luminous galaxies discovered by WISE

Science.gov (United States)

Vito, F.; Brandt, W. N.; Stern, D.; Assef, R. J.; Chen, C.-T. J.; Brightman, M.; Comastri, A.; Eisenhardt, P.; Garmire, G. P.; Hickox, R.; Lansbury, G.; Tsai, C.-W.; Walton, D. J.; Wu, J. W.

2018-03-01

Hot dust-obscured galaxies (DOGs) are hyperluminous (L8-1000 μm > 1013 L⊙) infrared galaxies with extremely high (up to hundreds of K) dust temperatures. The sources powering both their extremely high luminosities and dust temperatures are thought to be deeply buried and rapidly accreting supermassive black holes (SMBHs). Hot DOGs could therefore represent a key evolutionary phase in which the SMBH growth peaks. X-ray observations can be used to study their obscuration levels and luminosities. In this work, we present the X-ray properties of the 20 most luminous (Lbol ≳ 1014 L⊙) known hot DOGs at z = 2-4.6. Five of them are covered by long-exposure (10-70 ks) Chandra and XMM-Newton observations, with three being X-ray detected, and we study their individual properties. One of these sources (W0116-0505) is a Compton-thick candidate, with column density NH = (1.0-1.5) × 1024 cm-2 derived from X-ray spectral fitting. The remaining 15 hot DOGs have been targeted by a Chandra snapshot (3.1 ks) survey. None of these 15 are individually detected; therefore, we applied a stacking analysis to investigate their average emission. From hardness ratio analysis, we constrained the average obscuring column density and intrinsic luminosity to be log NH (cm-2) > 23.5 and LX ≳ 1044 erg s-1, which are consistent with results for individually detected sources. We also investigated the LX-L6 μm and LX-Lbol relations, finding hints that hot DOGs are typically X-ray weaker than expected, although larger samples of luminous obscured quasi-stellar objects are needed to derive solid conclusions.

Interactome Screening Identifies the ER Luminal Chaperone Hsp47 as a Regulator of the Unfolded Protein Response Transducer IRE1α.

Science.gov (United States)

Sepulveda, Denisse; Rojas-Rivera, Diego; Rodríguez, Diego A; Groenendyk, Jody; Köhler, Andres; Lebeaupin, Cynthia; Ito, Shinya; Urra, Hery; Carreras-Sureda, Amado; Hazari, Younis; Vasseur-Cognet, Mireille; Ali, Maruf M U; Chevet, Eric; Campos, Gisela; Godoy, Patricio; Vaisar, Tomas; Bailly-Maitre, Béatrice; Nagata, Kazuhiro; Michalak, Marek; Sierralta, Jimena; Hetz, Claudio

2018-01-18

Maintenance of endoplasmic reticulum (ER) proteostasis is controlled by a dynamic signaling network known as the unfolded protein response (UPR). IRE1α is a major UPR transducer, determining cell fate under ER stress. We used an interactome screening to unveil several regulators of the UPR, highlighting the ER chaperone Hsp47 as the major hit. Cellular and biochemical analysis indicated that Hsp47 instigates IRE1α signaling through a physical interaction. Hsp47 directly binds to the ER luminal domain of IRE1α with high affinity, displacing the negative regulator BiP from the complex to facilitate IRE1α oligomerization. The regulation of IRE1α signaling by Hsp47 is evolutionarily conserved as validated using fly and mouse models of ER stress. Hsp47 deficiency sensitized cells and animals to experimental ER stress, revealing the significance of Hsp47 to global proteostasis maintenance. We conclude that Hsp47 adjusts IRE1α signaling by fine-tuning the threshold to engage an adaptive UPR. Copyright © 2018 Elsevier Inc. All rights reserved.

Luminal and basal-like breast cancer cells show increased migration induced by hypoxia, mediated by an autocrine mechanism

International Nuclear Information System (INIS)

Voss, Melanie J; Möller, Mischa F; Powe, Desmond G; Niggemann, Bernd; Zänker, Kurt S; Entschladen, Frank

2011-01-01

Some breast cancer patients receiving anti-angiogenic treatment show increased metastases, possibly as a result of induced hypoxia. The effect of hypoxia on tumor cell migration was assessed in selected luminal, post-EMT and basal-like breast carcinoma cell lines. Migration was assessed in luminal (MCF-7), post-EMT (MDA-MB-231, MDA-MB-435S), and basal-like (MDA-MB-468) human breast carcinoma cell lines under normal and oxygen-deprived conditions, using a collagen-based assay. Cell proliferation was determined, secreted cytokine and chemokine levels were measured using flow-cytometry and a bead-based immunoassay, and the hypoxic genes HIF-1α and CA IX were assessed using PCR. The functional effect of tumor-cell conditioned medium on the migration of neutrophil granulocytes (NG) was tested. Hypoxia caused increased migratory activity but not proliferation in all tumor cell lines, involving the release and autocrine action of soluble mediators. Conditioned medium (CM) from hypoxic cells induced migration in normoxic cells. Hypoxia changed the profile of released inflammatory mediators according to cell type. Interleukin-8 was produced only by post-EMT and basal-like cell lines, regardless of hypoxia. MCP-1 was produced by MDA-MB-435 and -468 cells, whereas IL-6 was present only in MDA-MB-231. IL-2, TNF-α, and NGF production was stimulated by hypoxia in MCF-7 cells. CM from normoxic and hypoxic MDA-MB-231 and MDA-MB-435S cells and hypoxic MCF-7 cells, but not MDA-MB-468, induced NG migration. Hypoxia increases migration by the autocrine action of released signal substances in selected luminal and basal-like breast carcinoma cell lines which might explain why anti-angiogenic treatment can worsen clinical outcome in some patients

Vocal Fold Epithelial Response to Luminal Osmotic Perturbation

Science.gov (United States)

Sivasankar, Mahalakshmi; Fisher, Kimberly V.

2007-01-01

Purpose: Dry-air challenges increase the osmolarity of fluid lining the luminal surface of the proximal airway. The homeostasis of surface fluid is thought to be essential for voice production and laryngeal defense. Therefore, the authors hypothesized that viable vocal fold epithelium would generate a water flux to reduce an osmotic challenge (150…

ATP as a Multi-target Danger Signal in the Brain

Directory of Open Access Journals (Sweden)

Ricardo J Rodrigues

2015-04-01

Full Text Available ATP is released in an activity-dependent manner from different cell types in the brain, fulfilling different roles as a neurotransmitter, neuromodulator, astrocyte-to-neuron communication, propagating astrocytic responses and formatting microglia responses. This involves the activation of different ATP P2 receptors (P2R as well as adenosine receptors upon extracellular ATP catabolism by ecto-nucleotidases. Notably, brain noxious stimuli trigger a sustained increase of extracellular ATP, which plays a key role as danger signal in the brain. This involves a combined action of extracellular ATP in different cell types, namely increasing the susceptibility of neurons to damage, promoting astrogliosis and recruiting and formatting microglia to mount neuroinflammatory responses. Such actions involve the activation of different receptors, as heralded by neuroprotective effects resulting from blockade mainly of P2X7R, P2Y1R and adenosine A2A receptors (A2AR, which hierarchy, cooperation and/or redundancy is still not resolved. These pleiotropic functions of ATP as a danger signal in brain damage prompt a therapeutic interest to multi-target different purinergic receptors to provide maximal opportunities for neuroprotection.

The evolving roles of canonical WNT signaling in stem cells and tumorigenesis: Implications in targeted cancer therapies

Science.gov (United States)

Yang, Ke; Wang, Xin; Zhang, Hongmei; Wang, Zhongliang; Nan, Guoxin; Li, Yasha; Zhang, Fugui; Mohammed, Maryam K.; Haydon, Rex C.; Luu, Hue H.; Bi, Yang; He, Tong-Chuan

2015-01-01

The canonical WNT/β-catenin signaling pathway governs a myriad of biological processes underlying development and maintenance of adult tissue homeostasis, including regulation of stem cell self-renewal, cell proliferation, differentiation, and apoptosis. WNTs are secreted lipid-modified glycoproteins that act as short-range ligands to activate receptor-mediated signaling pathways. The hallmark of the canonical pathway is the activation of β-catenin mediated transcriptional activity. Canonical WNTs control the β-catenin dynamics as the cytoplasmic level of β-catenin is tightly regulated via phosphorylation by the ‘destruction complex’, consisting of glycogen synthase kinase 3β (GSK3β), casein kinase 1α (CK1α), the scaffold protein AXIN, and the tumor suppressor adenomatous polyposis coli (APC). Aberrant regulation of this signaling cascade is associated with varieties of human diseases, especially cancers. Over the past decade, significant progress has been made in understanding the mechanisms of canonical WNT signaling. In this review, we focus on the current understanding of WNT signaling at the extracellular, cytoplasmic membrane, and intracellular/nuclear levels, including the emerging knowledge of crosstalk with other pathways. Recent progresses in developing novel WNT pathway-targeted therapies will also be reviewed. Thus, this review is intended to serve as a refresher of the current understanding about the physiologic and pathogenic roles of WNT/β-catenin signaling pathway, and to outline potential therapeutic opportunities by targeting the canonical WNT pathway. PMID:26618721

The luminous and the grey

CERN Document Server

Batchelor, David

2014-01-01

Color surrounds us: the lush green hues of trees and grasses, the variant blues of water and the sky, the bright pops of yellow and red from flowers. But at the same time, color lies at the limits of language and understanding. In this absorbing sequel to Chromophobia-which addresses the extremes of love and loathing provoked by color since antiquity-David Batchelor charts color's more ambiguous terrain.   The Luminous and the Grey explores the places where color comes into being and where it fades away, probing when it begins and when it ends both in the imagination and in the material world.

Radioisotope treatment for benign strictures of non-vascular luminal organs

International Nuclear Information System (INIS)

Shin, Ji Hoon

2006-01-01

Tissue hyperplasia in one of the most frequently encountered complications when self-expanding stents are placed in benign non-vascular luminal organ strictures, thus causing of the lumen. The investigators postulated that ionizing irradiation could be applied to prevent restenosis caused by tissue hyperplasia in non-vascular luminal organs as it reduced coronary or peripheral arterial narrowing successfully. The authors combined β-irradiation using 188 Re-MAG 3 solution with balloon for animal and clinical studies because this new treatment approach had the advantages such as low penetration depth of β-ray, self-centering irradiation, and mechanical effect of balloon dilation over using γ-irradiation with afterloading devices. In this article, the concept and mechanism of radioisotope balloon dilation, and animal and clinical studies using radioisotope balloon dilation are reviewed

Presynaptic type III neuregulin1-ErbB signaling targets {alpha}7 nicotinic acetylcholine receptors to axons.

Science.gov (United States)

Hancock, Melissa L; Canetta, Sarah E; Role, Lorna W; Talmage, David A

2008-05-05

Type III Neuregulin1 (Nrg1) isoforms are membrane-tethered proteins capable of participating in bidirectional juxtacrine signaling. Neuronal nicotinic acetylcholine receptors (nAChRs), which can modulate the release of a rich array of neurotransmitters, are differentially targeted to presynaptic sites. We demonstrate that Type III Nrg1 back signaling regulates the surface expression of alpha7 nAChRs along axons of sensory neurons. Stimulation of Type III Nrg1 back signaling induces an increase in axonal surface alpha7 nAChRs, which results from a redistribution of preexisting intracellular pools of alpha7 rather than from increased protein synthesis. We also demonstrate that Type III Nrg1 back signaling activates a phosphatidylinositol 3-kinase signaling pathway and that activation of this pathway is required for the insertion of preexisting alpha7 nAChRs into the axonal plasma membrane. These findings, in conjunction with prior results establishing that Type III Nrg1 back signaling controls gene transcription, demonstrate that Type III Nrg1 back signaling can regulate both short-and long-term changes in neuronal function.

Presynaptic type III neuregulin1-ErbB signaling targets alpha7 nicotinic acetylcholine receptors to axons.

Science.gov (United States)

Hancock, Melissa L; Canetta, Sarah E; Role, Lorna W; Talmage, David A

2008-06-01

Type III Neuregulin1 (Nrg1) isoforms are membrane-tethered proteins capable of participating in bidirectional juxtacrine signaling. Neuronal nicotinic acetylcholine receptors (nAChRs), which can modulate the release of a rich array of neurotransmitters, are differentially targeted to presynaptic sites. We demonstrate that Type III Nrg1 back signaling regulates the surface expression of alpha7 nAChRs along axons of sensory neurons. Stimulation of Type III Nrg1 back signaling induces an increase in axonal surface alpha7 nAChRs, which results from a redistribution of preexisting intracellular pools of alpha7 rather than from increased protein synthesis. We also demonstrate that Type III Nrg1 back signaling activates a phosphatidylinositol 3-kinase signaling pathway and that activation of this pathway is required for the insertion of preexisting alpha7 nAChRs into the axonal plasma membrane. These findings, in conjunction with prior results establishing that Type III Nrg1 back signaling controls gene transcription, demonstrate that Type III Nrg1 back signaling can regulate both short-and long-term changes in neuronal function.

Presynaptic Type III Neuregulin1-ErbB signaling targets α7 nicotinic acetylcholine receptors to axons

Science.gov (United States)

Hancock, Melissa L.; Canetta, Sarah E.; Role, Lorna W.; Talmage, David A.

2008-01-01

Type III Neuregulin1 (Nrg1) isoforms are membrane-tethered proteins capable of participating in bidirectional juxtacrine signaling. Neuronal nicotinic acetylcholine receptors (nAChRs), which can modulate the release of a rich array of neurotransmitters, are differentially targeted to presynaptic sites. We demonstrate that Type III Nrg1 back signaling regulates the surface expression of α7 nAChRs along axons of sensory neurons. Stimulation of Type III Nrg1 back signaling induces an increase in axonal surface α7 nAChRs, which results from a redistribution of preexisting intracellular pools of α7 rather than from increased protein synthesis. We also demonstrate that Type III Nrg1 back signaling activates a phosphatidylinositol 3-kinase signaling pathway and that activation of this pathway is required for the insertion of preexisting α7 nAChRs into the axonal plasma membrane. These findings, in conjunction with prior results establishing that Type III Nrg1 back signaling controls gene transcription, demonstrate that Type III Nrg1 back signaling can regulate both short-and long-term changes in neuronal function. PMID:18458158

Direct Targeting of β-Catenin by a Small Molecule Stimulates Proteasomal Degradation and Suppresses Oncogenic Wnt/β-Catenin Signaling

Directory of Open Access Journals (Sweden)

So-Young Hwang

2016-06-01

Full Text Available The Wnt/β-catenin signaling pathway plays a major role in tissue homeostasis, and its dysregulation can lead to various human diseases. Aberrant activation of β-catenin is oncogenic and is a critical driver in the development and progression of human cancers. Despite the significant potential of targeting the oncogenic β-catenin pathway for cancer therapy, the development of specific inhibitors remains insufficient. Using a T cell factor (TCF-dependent luciferase-reporter system, we screened for small-molecule compounds that act against Wnt/β-catenin signaling and identified MSAB (methyl 3-{[(4-methylphenylsulfonyl]amino}benzoate as a selective inhibitor of Wnt/β-catenin signaling. MSAB shows potent anti-tumor effects selectively on Wnt-dependent cancer cells in vitro and in mouse cancer models. MSAB binds to β-catenin, promoting its degradation, and specifically downregulates Wnt/β-catenin target genes. Our findings might represent an effective therapeutic strategy for cancers addicted to the Wnt/β-catenin signaling pathway.

Cell signaling heterogeneity is modulated by both cell-intrinsic and -extrinsic mechanisms: An integrated approach to understanding targeted therapy.

Science.gov (United States)

Kim, Eunjung; Kim, Jae-Young; Smith, Matthew A; Haura, Eric B; Anderson, Alexander R A

2018-03-01

During the last decade, our understanding of cancer cell signaling networks has significantly improved, leading to the development of various targeted therapies that have elicited profound but, unfortunately, short-lived responses. This is, in part, due to the fact that these targeted therapies ignore context and average out heterogeneity. Here, we present a mathematical framework that addresses the impact of signaling heterogeneity on targeted therapy outcomes. We employ a simplified oncogenic rat sarcoma (RAS)-driven mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase-protein kinase B (PI3K-AKT) signaling pathway in lung cancer as an experimental model system and develop a network model of the pathway. We measure how inhibition of the pathway modulates protein phosphorylation as well as cell viability under different microenvironmental conditions. Training the model on this data using Monte Carlo simulation results in a suite of in silico cells whose relative protein activities and cell viability match experimental observation. The calibrated model predicts distributional responses to kinase inhibitors and suggests drug resistance mechanisms that can be exploited in drug combination strategies. The suggested combination strategies are validated using in vitro experimental data. The validated in silico cells are further interrogated through an unsupervised clustering analysis and then integrated into a mathematical model of tumor growth in a homogeneous and resource-limited microenvironment. We assess posttreatment heterogeneity and predict vast differences across treatments with similar efficacy, further emphasizing that heterogeneity should modulate treatment strategies. The signaling model is also integrated into a hybrid cellular automata (HCA) model of tumor growth in a spatially heterogeneous microenvironment. As a proof of concept, we simulate tumor responses to targeted therapies in a spatially segregated tissue structure containing tumor

GCN5 Regulates FGF Signaling and Activates Selective MYC Target Genes during Early Embryoid Body Differentiation

Directory of Open Access Journals (Sweden)

Li Wang

2018-01-01

Full Text Available Precise control of gene expression during development is orchestrated by transcription factors and co-regulators including chromatin modifiers. How particular chromatin-modifying enzymes affect specific developmental processes is not well defined. Here, we report that GCN5, a histone acetyltransferase essential for embryonic development, is required for proper expression of multiple genes encoding components of the fibroblast growth factor (FGF signaling pathway in early embryoid bodies (EBs. Gcn5−/− EBs display deficient activation of ERK and p38, mislocalization of cytoskeletal components, and compromised capacity to differentiate toward mesodermal lineage. Genomic analyses identified seven genes as putative direct targets of GCN5 during early differentiation, four of which are cMYC targets. These findings established a link between GCN5 and the FGF signaling pathway and highlighted specific GCN5-MYC partnerships in gene regulation during early differentiation.

DACH1: its role as a classifier of long term good prognosis in luminal breast cancer.

Directory of Open Access Journals (Sweden)

Desmond G Powe

Full Text Available BACKGROUND: Oestrogen receptor (ER positive (luminal tumours account for the largest proportion of females with breast cancer. Theirs is a heterogeneous disease presenting clinical challenges in managing their treatment. Three main biological luminal groups have been identified but clinically these can be distilled into two prognostic groups in which Luminal A are accorded good prognosis and Luminal B correlate with poor prognosis. Further biomarkers are needed to attain classification consensus. Machine learning approaches like Artificial Neural Networks (ANNs have been used for classification and identification of biomarkers in breast cancer using high throughput data. In this study, we have used an artificial neural network (ANN approach to identify DACH1 as a candidate luminal marker and its role in predicting clinical outcome in breast cancer is assessed. MATERIALS AND METHODS: A reiterative ANN approach incorporating a network inferencing algorithm was used to identify ER-associated biomarkers in a publically available cDNA microarray dataset. DACH1 was identified in having a strong influence on ER associated markers and a positive association with ER. Its clinical relevance in predicting breast cancer specific survival was investigated by statistically assessing protein expression levels after immunohistochemistry in a series of unselected breast cancers, formatted as a tissue microarray. RESULTS: Strong nuclear DACH1 staining is more prevalent in tubular and lobular breast cancer. Its expression correlated with ER-alpha positive tumours expressing PgR, epithelial cytokeratins (CK18/19 and 'luminal-like' markers of good prognosis including FOXA1 and RERG (p<0.05. DACH1 is increased in patients showing longer cancer specific survival and disease free interval and reduced metastasis formation (p<0.001. Nuclear DACH1 showed a negative association with markers of aggressive growth and poor prognosis. CONCLUSION: Nuclear DACH1 expression

Glossiness and perishable food quality: visual freshness judgment of fish eyes based on luminance distribution.

Science.gov (United States)

Murakoshi, Takuma; Masuda, Tomohiro; Utsumi, Ken; Tsubota, Kazuo; Wada, Yuji

2013-01-01

Previous studies have reported the effects of statistics of luminance distribution on visual freshness perception using pictures which included the degradation process of food samples. However, these studies did not examine the effect of individual differences between the same kinds of food. Here we elucidate whether luminance distribution would continue to have a significant effect on visual freshness perception even if visual stimuli included individual differences in addition to the degradation process of foods. We took pictures of the degradation of three fishes over 3.29 hours in a controlled environment, then cropped square patches of their eyes from the original images as visual stimuli. Eleven participants performed paired comparison tests judging the visual freshness of the fish eyes at three points of degradation. Perceived freshness scores (PFS) were calculated using the Bradley-Terry Model for each image. The ANOVA revealed that the PFS for each fish decreased as the degradation time increased; however, the differences in the PFS between individual fish was larger for the shorter degradation time, and smaller for the longer degradation time. A multiple linear regression analysis was conducted in order to determine the relative importance of the statistics of luminance distribution of the stimulus images in predicting PFS. The results show that standard deviation and skewness in luminance distribution have a significant influence on PFS. These results show that even if foodstuffs contain individual differences, visual freshness perception and changes in luminance distribution correlate with degradation time.

Classification of radioactive self-luminous light sources - approved 1975. NBS Handbook 116

International Nuclear Information System (INIS)

Anon.

1977-01-01

The standard establishes the classification of certain radioactive self-luminous light sources according to radionuclide, type of source, activity, and performance requirements. The objectives are to establish minimum prototype testing requirements for radioactive self-luminous light sources, to promote uniformity of marking such sources, and to establish minimum physical performance for such sources. The standard is primarily directed toward assuring adequate containment of the radioactive material. Testing procedures and classification designations are specified for discoloration, temperature, thermal shock, reduced pressure, impact, vibration, and immersion. A range of test requirements is presented according to intended usage and source activity

Directionality and signal amplification in cryogenic dark matter detection

International Nuclear Information System (INIS)

More, T.

1996-05-01

A mounting body of evidence suggests that most of the mass in our universe is not contained in stars, but rather exists in some non- luminous form. The evidence comes independently from astronomical observation, cosmological theory, and particle physics. All of this missing mass is collectively referred to as dark matter. In this thesis we discuss two ways to improve the performance of dark matter detectors based on the measurement of ballistic phonons. First, we address the issue of signal identification through solitons. Secondly, we discuss a method for lowering the detection threshold and improving the energy sensitivity: amplifying phonons through the evaporation of helium atoms from a superfluid film coating the target and the adsorption of the evaporated atoms onto a helium-free substrate. A phonon amplifier would also be of use in many other applications in which a few phonons are to be measured at low temperatures. Factors contributing to the low amplifier gains achieved thus far are described and proposals for avoiding them are analyzed and discussed. 101 refs., 30 figs., 2 tabs

Wnt and Notch signaling pathway involved in wound healing by targeting c-Myc and Hes1 separately.

Science.gov (United States)

Shi, Yan; Shu, Bin; Yang, Ronghua; Xu, Yingbin; Xing, Bangrong; Liu, Jian; Chen, Lei; Qi, Shaohai; Liu, Xusheng; Wang, Peng; Tang, Jinming; Xie, Julin

2015-06-16

Wnt and Notch signaling pathways are critically involved in relative cell fate decisions within the development of cutaneous tissues. Moreover, several studies identified the above two pathways as having a significant role during wound healing. However, their biological effects during cutaneous tissues repair are unclear. We employed a self-controlled model (Sprague-Dawley rats with full-thickness skin wounds) to observe the action and effect of Wnt/β-catenin and Notch signalings in vivo. The quality of wound repair relevant to the gain/loss-of-function Wnt/β-catenin and Notch activation was estimated by hematoxylin-and-eosin and Masson staining. Immunofluorescence analysis and Western blot analysis were used to elucidate the underlying mechanism of the regulation of Wnt and Notch signaling pathways in wound healing. Meanwhile, epidermal stem cells (ESCs) were cultured in keratinocyte serum-free medium with Jaggedl or in DAPT (N-[(3,5-difluorophenyl)acetyl]-L-alanyl-2-phenyl]glycine-1,1-dimethylethyl) to investigate whether the interruption of Notch signaling contributes to the expression of Wnt/β-catenin signaling. The results showed that in vivo the gain-of-function Wnt/β-catenin and Notch activation extended the ability to promote wound closure. We further determined that activation or inhibition of Wnt signaling and Notch signaling can affect the proliferation of ESCs, the differentiation and migration of keratinocytes, and follicle regeneration by targeting c-Myc and Hes1, which ultimately lead to enhanced or delayed wound healing. Furthermore, Western blot analysis suggested that the two pathways might interact in vivo and in vitro. These results suggest that Wnt and Notch signalings play important roles in cutaneous repair by targeting c-Myc and Hes1 separately. What's more, interaction between the above two pathways might act as a vital role in regulation of wound healing.

The Highly Luminous Type Ibn Supernova ASASSN-14ms

DEFF Research Database (Denmark)

Vallely, P. J.; Prieto, J. L.; Stanek, K. Z.

2018-01-01

We present photometric and spectroscopic follow-up observations of the highly luminous Type Ibn supernova ASASSN-14ms, which was discovered on UT 2014-12-26.61 at $m_V \\sim 16.5$. With a peak absolute $V$-band magnitude brighter than $-20.5$, a peak bolometric luminosity of $1.7 \\times 10......^{44}$ ergs s$^{-1}$, and a total radiated energy of $2.1 \\times 10^{50}$ ergs, ASASSN-14ms is one of the most luminous Type Ibn supernovae yet discovered. In simple models, the most likely power source for this event is a combination of the radioactive decay of $^{56}$Ni and $^{56}$Co at late times...... and the interaction of supernova ejecta with the progenitor's circumstellar medium at early times, although we cannot rule out the possibility of a magnetar-powered light curve. The presence of a dense circumstellar medium is indicated by the intermediate-width He I features in the spectra. The faint ($m_g \\sim 21...

A CANDIDATE FOR THE MOST LUMINOUS OB ASSOCIATION IN THE GALAXY

International Nuclear Information System (INIS)

Rahman, Mubdi; Matzner, Christopher; Moon, Dae-Sik

2011-01-01

The Milky Way harbors giant H II regions, which may be powered by star complexes more luminous than any known Galactic OB association. Being across the disk of the Galaxy, however, these brightest associations are severely extinguished and confused. We present a search for one such association toward the most luminous H II region in the recent catalog by Murray and Rahman, which, at ∼9.7 kpc, has a recombination rate of ∼7 x 10 51 s -1 . Prior searches have identified only small-scale clustering around the rim of this shell-like region, but the primary association has not previously been identified. We apply a near-infrared color selection and find an overdensity of point sources toward its southern central part. The colors and magnitudes of these excess sources are consistent with O- and early B-type stars at extinctions 0.96 K < 1.2, and they are sufficiently numerous (406 ± 102 after subtraction of field sources) to ionize the surrounding H II region, making this a candidate for the most luminous OB association in the Galaxy. We reject an alternate theory, in which the apparent excess is caused by localized extinction, as inconsistent with source demographics.

Os efeitos da idade na percepção visual de grades senoidais em luminância baixa The effects of age on visual perception of sine-wave gratings at low luminance

Directory of Open Access Journals (Sweden)

Natanael Antonio dos Santos

2006-01-01

Full Text Available O objetivo deste trabalho foi investigar a função de sensibilidade ao contraste (FSC de adultos e idosos (20-23, 30-39, 40-49, 50-59, 60-69 anos para grades senoidais de 0,25 a 2 cpg em luminância baixa. Todos os participantes apresentavam acuidade visual normal e se encontravam livres de doenças oculares identificáveis. Foram estimados limiares de contraste para 30 participantes (seis em cada faixa etária utilizando o método psicofísico da escolha forçada. Neste método, os participantes tinham que escolher um estímulo contendo uma freqüência de teste (grade senoidal em baixo contraste ou um estímulo neutro com luminância média de 0,7 cd/m². Os resultados mostraram que os grupos de 50-59 e 60-69 anos apresentaram prejuízos significativos na FSC nas freqüências espaciais de 1 e 2 cpg comparados ao grupo de 20-23 anos. Estes resultados sugerem alterações relacionadas à idade na FSC de freqüências espaciais em níveis baixos de luminância.The aim of this work was to investigate the contrast sensitivity function for sine-wave gratings in the range between 0.25-2 cpd in young and older adults (20-23, 30-39, 40-49, 50-59, 60-69 years old using low luminance. All subjects were free from identifiable ocular disease and had normal acuity. We measured the contrast thresholds for 30 participants (six volunteers in each age using the psychophysical forced-choice staircase method. In this method the volunteers had to choose the stimulus containing a test frequency at low contrast (e.g., a sine-wave grating, or another neutral stimulus at mean luminance (0.7 cd/m². The results showed significant changes of CSF for sine-wave gratings at 1 and 2 cpd for the adults 50-59 and 60-69 years old compared to the adults of 20-23 years old. These results suggest age-related changes in the CSF for sine-wave grating at low luminance levels.

Transferable chloramphenicol resistance determinant in luminous Vibrio harveyi from penaeid shrimp Penaeus monodon larvae

Directory of Open Access Journals (Sweden)

Thangapalam Jawahar Abraham

2016-12-01

Full Text Available Antibiotic-resistant luminous Vibrio harveyi strains isolated from Penaeus monodon larvae were screened for the possession of transferable resistance determinants. All the strains were resistant to chloramphenicol and the determinant coding for chloramphenicol resistance was transferred to Escherichia coli at frequencies of 9.50x10-4 to 4.20x10-4. The results probably suggest the excessive use of chloramphenicol in shrimp hatcheries to combat luminous vibriosis.

10 CFR 32.101 - Schedule B-prototype tests for luminous safety devices for use in aircraft.

Science.gov (United States)

2010-01-01

....101 Schedule B—prototype tests for luminous safety devices for use in aircraft. An applicant for a... 10 Energy 1 2010-01-01 2010-01-01 false Schedule B-prototype tests for luminous safety devices for use in aircraft. 32.101 Section 32.101 Energy NUCLEAR REGULATORY COMMISSION SPECIFIC DOMESTIC LICENSES...

SN 2010U: A LUMINOUS NOVA IN NGC 4214

International Nuclear Information System (INIS)

Humphreys, Roberta M.; Helton, L. Andrew; Prieto, Jose L.; Rosenfield, Philip; Williams, Benjamin; Murphy, Jeremiah; Dalcanton, Julianne; Gilbert, Karoline; Kochanek, Christopher S.; Stanek, K. Z.; Khan, Rubab; Szczygiel, Dorota; Mogren, Karen; Fesen, Robert A.; Milisavljevic, Dan

2010-01-01

The luminosity, light curve, post-maximum spectrum, and lack of a progenitor on deep pre-outburst images suggest that SN 2010U was a luminous, fast nova. Its outburst magnitude is consistent with that for a fast nova using the maximum magnitude-rate of decline relationship for classical novae.

EXTENDED [C II] EMISSION IN LOCAL LUMINOUS INFRARED GALAXIES

International Nuclear Information System (INIS)

Díaz-Santos, T.; Armus, L.; Surace, J. A.; Charmandaris, V.; Stacey, G.; Murphy, E. J.; Haan, S.; Stierwalt, S.; Evans, A. S.; Malhotra, S.; Appleton, P.; Inami, H.; Magdis, G. E.; Elbaz, D.; Mazzarella, J. M.; Xu, C. K.; Lu, N.; Howell, J. H.; Van der Werf, P. P.; Meijerink, R.

2014-01-01

We present Herschel/PACS observations of extended [C II] 157.7 μm line emission detected on ∼1-10 kpc scales in 60 local luminous infrared galaxies (LIRGs) from the Great Observatories All-sky LIRG Survey. We find that most of the extra-nuclear emission show [C II]/FIR ratios ≥4 × 10 –3 , larger than the mean ratio seen in the nuclei, and similar to those found in the extended disks of normal star-forming galaxies and the diffuse interstellar medium of our Galaxy. The [C II] ''deficits'' found in the most luminous local LIRGs are therefore restricted to their nuclei. There is a trend for LIRGs with warmer nuclei to show larger differences between their nuclear and extra-nuclear [C II]/FIR ratios. We find an anti-correlation between [C II]/FIR and the luminosity surface density, Σ IR , for the extended emission in the spatially resolved galaxies. However, there is an offset between this trend and that found for the LIRG nuclei. We use this offset to derive a beam filling-factor for the star-forming regions within the LIRG disks of ∼6% relative to their nuclei. We confront the observed trend to photo-dissociation region models and find that the slope of the correlation is much shallower than the model predictions. Finally, we compare the correlation found between [C II]/FIR and Σ IR with measurements of high-redshift starbursting IR-luminous galaxies

Measurement of luminance noise and chromaticity noise of LCDs with a colorimeter and a color camera

Science.gov (United States)

Roehrig, H.; Dallas, W. J.; Krupinski, E. A.; Redford, Gary R.

2007-09-01

This communication focuses on physical evaluation of image quality of displays for applications in medical imaging. In particular we were interested in luminance noise as well as chromaticity noise of LCDs. Luminance noise has been encountered in the study of monochrome LCDs for some time, but chromaticity noise is a new type of noise which has been encountered first when monochrome and color LCDs were compared in an ROC study. In this present study one color and one monochrome 3 M-pixel LCDs were studied. Both were DICOM calibrated with equal dynamic range. We used a Konica Minolta Chroma Meter CS-200 as well as a Foveon color camera to estimate luminance and chrominance variations of the displays. We also used a simulation experiment to estimate luminance noise. The measurements with the colorimeter were consistent. The measurements with the Foveon color camera were very preliminary as color cameras had never been used for image quality measurements. However they were extremely promising. The measurements with the colorimeter and the simulation results showed that the luminance and chromaticity noise of the color LCD were larger than that of the monochrome LCD. Under the condition that an adequate calibration method and image QA/QC program for color displays are available, we expect color LCDs may be ready for radiology in very near future.

Informational primacy of visual dimensions: specialized roles for luminance and chromaticity in figure-ground perception.

Science.gov (United States)

Yamagishi, N; Melara, R D

2001-07-01

Three experiments were conducted to examine the distinct contributions of two visual dimensions to figure-ground segregation. In each experiment, pattern identification was assessed by asking observers to judge whether a near-threshold test pattern was the same or different in shape to a high-contrast comparison pattern. A test pattern could differ from its background along one dimension, either luminance (luminance tasks) or chromaticity (chromaticity tasks). In each task, performance in a baseline condition, in which the test pattern was intact, was compared with performance in each of several degradation conditions, in which either the contour or the surface of the figure was degraded, using either partial occlusion (Experiment 1) or ramping (Experiments 2 and 3) of figure-ground differences. In each experiment, performance in luminance tasks was worst when the contour was degraded, whereas performance in chromaticity tasks was worst when the surface was degraded. This interaction was found even when spatial frequencies were fixed across test patterns by low-pass filtering. The results are consistent with a late (postfiltering) dual-mechanism system that processes luminance information to extract boundary representations and chromaticity information to extract surface representations.

High expression of ZNF703 independent of amplification indicates worse prognosis in patients with luminal B breast cancer

International Nuclear Information System (INIS)

Reynisdottir, Inga; Arason, Adalgeir; Einarsdottir, Berglind O; Gunnarsson, Haukur; Staaf, Johan; Vallon-Christersson, Johan; Jonsson, Goran; Ringnér, Markus; Agnarsson, Bjarni A; Olafsdottir, Kristrun; Fagerholm, Rainer; Einarsdottir, Thorbjorg; Johannesdottir, Gudrun; Johannsson, Oskar Thor; Nevanlinna, Heli; Borg, Ake; Barkardottir, Rosa Bjork

2013-01-01

Amplification of 8p12-p11 is relatively common in breast cancer and several genes within the region have been suggested to affect breast tumor progression. The aim of the study was to map the amplified 8p12-p11 region in a large set of breast tumors in an effort to identify the genetic driver and to explore its impact on tumor progression and prognosis. Copy number alterations (CNAs) were mapped in 359 tumors, and gene expression data from 577 tumors (359 tumors included) were correlated with CNA, clinical–pathological factors, and protein expression (39 tumors). 8p12-p11 was amplified in 11.4% of tumors. The smallest region of amplification harbored one full-length gene, ZNF703. ZNF703 mRNA expression was significantly higher in estrogen receptor (ER)-positive than ER-negative tumors (P = 2 × 10 −16 ), a reflection of high expression in luminal tumors. Forty-eight percent of tumors with ZNF703 amplification were luminal B tumors in which the best correlation between DNA copy number and mRNA was seen (P = 1.2 × 10 −7 ) as well as correlation between mRNA and protein expression (P = 0.02). High ZNF703 mRNA correlated with poor survival in patients with ER-positive luminal B tumors (log rank P = 0.04). Furthermore, high ZNF703 mRNA expression correlated with poor outcome in patients with ZNF703 copy number neutral, ER-positive, luminal B tumors (log rank P = 0.004). The results support ZNF703 as the driver gene of the 8p12 amplification and suggest that independent of amplification, high expression of the gene affects prognosis in luminal B tumors. Our mapping of 8p12-p11 and analyses of ZNF703 mRNA and protein expression in breast tumors support ZNF703 as an oncogene in luminal B tumors. High ZNF703 expression, independent of the amplification, correlated with worse prognosis for the breast cancer patients with ER-positive luminal tumors, particularly of the luminal B subtype

Dopamine signaling: target in glioblastoma

Czech Academy of Sciences Publication Activity Database

Bartek, Jiří; Hodný, Zdeněk

2014-01-01

Roč. 5, č. 5 (2014), 1116-1117 ISSN 1949-2553 Institutional support: RVO:68378050 Keywords : Dopamine signaling * glioblastoma * MAPK Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 6.359, year: 2014

Light production in the luminous fishes Photoblepharon and Anomalops from the Banda Islands.

Science.gov (United States)

Haneda, Y; Tsuji, F I

1971-07-09

The unresolved mechanism of light production in Photoblepharon and Anomalops has been reinvestigated in fresh and preserved material. Based on biochemical evidence obtained with emulsions and cell-free extracts of the organs, especially the stimulation of light with reduced flavin mononucleotide, and on electron microscopy of organ sections showing the presence of numerous bacteria, we conclude that the light is produced by symbiotic luminous bacteria. Because of the continuing failure to cultivate the luminous bacteria and because of their morphology, we suggest that the bacteria are of a primitive type called bacteroids.

Low luminance/eyes closed and monochromatic stimulations reduce variability of flash visual evoked potential latency

Directory of Open Access Journals (Sweden)

Senthil Kumar Subramanian

2013-01-01

Full Text Available Context: Visual evoked potentials are useful in investigating the physiology and pathophysiology of the human visual system. Flash visual evoked potential (FVEP, though technically easier, has less clinical utility because it shows great variations in both latency and amplitude for normal subjects. Aim: To study the effect of eye closure, low luminance, and monochromatic stimulation on the variability of FVEPs. Subjects and Methods: Subjects in self-reported good health in the age group of 18-30 years were divided into three groups. All participants underwent FVEP recording with eyes open and with white light at 0.6 J luminance (standard technique. Next recording was done in group 1 with closed eyes, group 2 with 1.2 and 20 J luminance, and group 3 with red and blue lights, while keeping all the other parameters constant. Two trials were given for each eye, for each technique. The same procedure was repeated at the same clock time on the following day. Statistical Analysis: Variation in FVEP latencies between the individuals (interindividual variability and the variations within the same individual for four trials (intraindividual variability were assessed using coefficient of variance (COV. The technique with lower COV was considered the better method. Results: Recording done with closed eyes, 0.6 J luminance, and monochromatic light (blue > red showed lower interindividual and intraindividual variability in P2 and N2 as compared to standard techniques. Conclusions: Low luminance flash stimulations and monochromatic light will reduce FVEP latency variability and may be clinically useful modifications of FVEP recording technique.

Endogenous myoglobin in human breast cancer is a hallmark of luminal cancer phenotype.

Science.gov (United States)

Kristiansen, G; Rose, M; Geisler, C; Fritzsche, F R; Gerhardt, J; Lüke, C; Ladhoff, A-M; Knüchel, R; Dietel, M; Moch, H; Varga, Z; Theurillat, J-P; Gorr, T A; Dahl, E

2010-06-08

We aimed to clarify the incidence and the clinicopathological value of non-muscle myoglobin (Mb) in a large cohort of non-invasive and invasive breast cancer cases. Matched pairs of breast tissues from 10 patients plus 17 breast cell lines were screened by quantitative PCR for Mb mRNA. In addition, 917 invasive and 155 non-invasive breast cancer cases were analysed by immunohistochemistry for Mb expression and correlated to clinicopathological parameters and basal molecular characteristics including oestrogen receptor-alpha (ERalpha)/progesteron receptor (PR)/HER2, fatty acid synthase (FASN), hypoxia-inducible factor-1alpha (HIF-1alpha), HIF-2alpha, glucose transporter 1 (GLUT1) and carbonic anhydrase IX (CAIX). The spatial relationship of Mb and ERalpha or FASN was followed up by double immunofluorescence. Finally, the effects of estradiol treatment and FASN inhibition on Mb expression in breast cancer cells were analysed. Myoglobin mRNA was found in a subset of breast cancer cell lines; in microdissected tumours Mb transcript was markedly upregulated. In all, 71% of tumours displayed Mb protein expression in significant correlation with a positive hormone receptor status and better prognosis. In silico data mining confirmed higher Mb levels in luminal-type breast cancer. Myoglobin was also correlated to FASN, HIF-2alpha and CAIX, but not to HIF-1alpha or GLUT1, suggesting hypoxia to participate in its regulation. Double immunofluorescence showed a cellular co-expression of ERalpha or FASN and Mb. In addition, Mb levels were modulated on estradiol treatment and FASN inhibition in a cell model. We conclude that in breast cancer, Mb is co-expressed with ERalpha and co-regulated by oestrogen signalling and can be considered a hallmark of luminal breast cancer phenotype. This and its possible new role in fatty acid metabolism may have fundamental implications for our understanding of Mb in solid tumours.

The effects of age on visual perception of sine-wave gratings at low luminance / Os efeitos da idade na percepção visual de grades senoidais em luminância baixa

Directory of Open Access Journals (Sweden)

Natanael Antonio dos Santos

2006-01-01

Full Text Available The aim of this work was to investigate the contrast sensitivity function for sine-wave gratings in the range between 0.25-2 cpd in young and older adults (20-23, 30-39, 40-49, 50-59, 60-69 years old using low luminance. All subjects were free from identifiable ocular disease and had normal acuity. We measured the contrast thresholds for 30 participants (six volunteers in each age using the psychophysical forced-choice staircase method. In this method the volunteers had to choose the stimulus containing a test frequency at low contrast (e.g., a sine-wave grating, or another neutral stimulus at mean luminance (0.7 cd/m2. The results showed significant changes of CSF for sine-wave gratings at 1 and 2 cpd for the adults 50-59 and 60-69 years old compared to the adults of 20-23 years old. These results suggest age-related changes in the CSF for sine-wave grating at low luminance levels.

10 CFR 32.22 - Self-luminous products containing tritium, krypton-85 or promethium-147: Requirements for license...

Science.gov (United States)

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false Self-luminous products containing tritium, krypton-85 or... containing tritium, krypton-85 or promethium-147: Requirements for license to manufacture, process, produce... self-luminous products containing tritium, krypton-85, or promethium-147, or to initially transfer such...

Myeloproliferative neoplasms: JAK2 signaling pathway as a central target for therapy.

Science.gov (United States)

Pasquier, Florence; Cabagnols, Xenia; Secardin, Lise; Plo, Isabelle; Vainchenker, William

2014-09-01

The discovery of the JAK2V617F mutation followed by the discovery of other genetic abnormalities allowed important progress in the understanding of the pathogenesis and management of myeloproliferative neoplasms (MPN)s. Classical Breakpoint cluster region-Abelson (BCR-ABL)-negative neoplasms include 3 main disorders: essential thrombocythemia (ET), polycythemia vera (PV), and primary myelofibrosis (PMF). Genomic studies have shown that these disorders are more heterogeneous than previously thought with 3 main entities corresponding to different gene mutations: the JAK2 disorder, essentially due to JAK2V617F mutation, which includes nearly all PVs and a majority of ETs and PMFs with a continuum between these diseases and the myeloproliferative leukemia (MPL) and calreticulin (CALR) disorders, which include a fraction of ET and PMF. All of these mutations lead to a JAK2 constitutive activation. Murine models either with JAK2V617F or MPLW515L, but also with JAK2 or MPL germ line mutations found in hereditary thrombocytosis, have demonstrated that they are drivers of myeloproliferation. However, the myeloproliferative driver mutation is still unknown in approximately 15% of ET and PMF, but appears to also target the JAK/Signal Transducer and Activator of Transcription (STAT) pathway. However, other mutations in genes involved in epigenetics or splicing also can be present and can predate or follow mutations in signaling. They are involved either in clonal dominance or in phenotypic changes, more particularly in PMF. They can be associated with leukemic progression and might have an important prognostic value such as additional sex comb-like 1 mutations. Despite this heterogeneity, it is tempting to target JAK2 and its signaling for therapy. However in PMF, Adenosine Tri-Phosphate (ATP)-competitive JAK2 inhibitors have shown their interest, but also their important limitations. Thus, other approaches are required, which are discussed in this review. Copyright © 2014

Dynamic contrast-enhanced MRI in patients with luminal Crohn's disease

NARCIS (Netherlands)

Ziech, M. L. W.; Lavini, C.; Caan, M. W. A.; Nio, C. Y.; Stokkers, P. C. F.; Bipat, S.; Ponsioen, C. Y.; Nederveen, A. J.; Stoker, J.

2012-01-01

Objectives: To prospectively assess dynamic contrast-enhanced (DCE-)MRI as compared to conventional sequences in patients with luminal Crohn's disease. Methods: Patients with Crohn's disease undergoing MRI and ileocolonoscopy within 1 month had DCE-MRI (3T) during intravenous contrast injection of

Signal Processing of Ground Penetrating Radar Using Spectral Estimation Techniques to Estimate the Position of Buried Targets

Directory of Open Access Journals (Sweden)

Shanker Man Shrestha

2003-11-01

Full Text Available Super-resolution is very important for the signal processing of GPR (ground penetration radar to resolve closely buried targets. However, it is not easy to get high resolution as GPR signals are very weak and enveloped by the noise. The MUSIC (multiple signal classification algorithm, which is well known for its super-resolution capacity, has been implemented for signal and image processing of GPR. In addition, conventional spectral estimation technique, FFT (fast Fourier transform, has also been implemented for high-precision receiving signal level. In this paper, we propose CPM (combined processing method, which combines time domain response of MUSIC algorithm and conventional IFFT (inverse fast Fourier transform to obtain a super-resolution and high-precision signal level. In order to support the proposal, detailed simulation was performed analyzing SNR (signal-to-noise ratio. Moreover, a field experiment at a research field and a laboratory experiment at the University of Electro-Communications, Tokyo, were also performed for thorough investigation and supported the proposed method. All the simulation and experimental results are presented.

Profile of a Growing Urban School: The Lumin Experience

Science.gov (United States)

Ford, Terry

2015-01-01

This fairytale-come-true began with an idealistic public school teacher just out of college who lived in the neighborhood of her students. In stages, working with a community organizing group consisting mainly of concerned parents, Terry Ford founded what is now called Lumin Education, a network of campuses serving more than six hundred children…

Protein kinase C α is a central signaling node and therapeutic target for breast cancer stem cells.

Science.gov (United States)

Tam, Wai Leong; Lu, Haihui; Buikhuisen, Joyce; Soh, Boon Seng; Lim, Elgene; Reinhardt, Ferenc; Wu, Zhenhua Jeremy; Krall, Jordan A; Bierie, Brian; Guo, Wenjun; Chen, Xi; Liu, Xiaole Shirley; Brown, Myles; Lim, Bing; Weinberg, Robert A

2013-09-09

The epithelial-mesenchymal transition program becomes activated during malignant progression and can enrich for cancer stem cells (CSCs). We report that inhibition of protein kinase C α (PKCα) specifically targets CSCs but has little effect on non-CSCs. The formation of CSCs from non-stem cells involves a shift from EGFR to PDGFR signaling and results in the PKCα-dependent activation of FRA1. We identified an AP-1 molecular switch in which c-FOS and FRA1 are preferentially utilized in non-CSCs and CSCs, respectively. PKCα and FRA1 expression is associated with the aggressive triple-negative breast cancers, and the depletion of FRA1 results in a mesenchymal-epithelial transition. Hence, identifying molecular features that shift between cell states can be exploited to target signaling components critical to CSCs. Copyright © 2013 Elsevier Inc. All rights reserved.

Modulation of visual cortical excitability by working memory: effect of luminance contrast of mental imagery

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Zaira eCattaneo

2011-02-01

Full Text Available Although much is known about the impact of stimulus properties such as luminance contrast, spatial frequency and orientation on visually evoked neural activity, much less is known about how they modulate neural activity when they are properties of a mental image held in working memory (WM. Here we addressed this question by investigating how a parametric manipulation of an imagined stimulus attribute affects neuronal excitability in the early visual cortex. We manipulated luminance contrast, a stimulus property known to strongly affect the magnitude of neuronal responses in early visual areas. Luminance contrast modulated neuronal excitability, as assessed by the frequency of phosphenes induced by transcranial magnetic stimulation (TMS with the exact nature of this modulation depending on TMS intensity. These results point to a strong overlap in the neuronal processes underlying visual perception and mental imagery: not only does WM maintenance selectively engage neurons which are tuned to the maintained attribute (as has previously been shown, but the extent to which those neurons are activated depends on the luminance contrast (as is the case with visually-evoked responses. From a methodological viewpoint, these results suggest that assessment of visual cortical excitability using TMS is affected by the TMS intensity used to probe the neuronal population.

Contributions of contour frequency, amplitude, and luminance to the watercolor effect estimated by conjoint measurement.

Science.gov (United States)

Gerardin, Peggy; Devinck, Frédéric; Dojat, Michel; Knoblauch, Kenneth

2014-04-10

The watercolor effect is a long-range, assimilative, filling-in phenomenon induced by a pair of distant, wavy contours of different chromaticities. Here, we measured joint influences of the contour frequency and amplitude and the luminance of the interior contour on the strength of the effect. Contour pairs, each enclosing a circular region, were presented with two of the dimensions varying independently across trials (luminance/frequency, luminance/amplitude, frequency/amplitude) in a conjoint measurement paradigm (Luce & Tukey, 1964). In each trial, observers judged which of the stimuli evoked the strongest fill-in color. Control stimuli were identical except that the contours were intertwined and generated little filling-in. Perceptual scales were estimated by a maximum likelihood method (Ho, Landy, & Maloney, 2008). An additive model accounted for the joint contributions of any pair of dimensions. As shown previously using difference scaling (Devinck & Knoblauch, 2012), the strength increases with luminance of the interior contour. The strength of the phenomenon was nearly independent of the amplitude of modulation of the contour but increased with its frequency up to an asymptotic level. On average, the strength of the effect was similar along a given dimension regardless of the other dimension with which it was paired, demonstrating consistency of the underlying estimated perceptual scales.

Compact RGBY light sources with high luminance for laser display applications

Science.gov (United States)

Paschke, Katrin; Blume, Gunnar; Werner, Nils; Müller, André; Sumpf, Bernd; Pohl, Johannes; Feise, David; Ressel, Peter; Sahm, Alexander; Bege, Roland; Hofmann, Julian; Jedrzejczyk, Daniel; Tränkle, Günther

2018-02-01

Watt-class visible laser light with a high luminance can be created with high-power GaAs-based lasers either directly in the red spectral region or using single-pass second harmonic generation (SHG) for the colors in the blue-yellow spectral region. The concepts and results of red- and near infrared-emitting distributed Bragg reflector tapered lasers and master oscillator power amplifier systems as well as their application for SHG bench-top experiments and miniaturized modules are presented. Examples of these high-luminance light sources aiming at different applications such as flying spot display or holographic 3D cinema are discussed in more detail. The semiconductor material allows an easy adaptation of the wavelength allowing techniques such as six-primary color 3D projection or color space enhancement by adding a fourth yellow color.

First observations of transient luminous events in Indian sub-continent

DEFF Research Database (Denmark)

Singh, Rajesh; Maurya, Ajeet K.; Veenadhari, B.

2014-01-01

The article offers information on the initial observations of flashes of lightning discharge observed above thunderstorms. It mentions that the transient luminous events (TLE) are classified on the basis of their geometrical shape and luminosity into Sprites, Halos and Blue Starters. It also focu...

A model system for targeted drug release triggered by biomolecular signals logically processed through enzyme logic networks.

Science.gov (United States)

Mailloux, Shay; Halámek, Jan; Katz, Evgeny

2014-03-07

A new Sense-and-Act system was realized by the integration of a biocomputing system, performing analytical processes, with a signal-responsive electrode. A drug-mimicking release process was triggered by biomolecular signals processed by different logic networks, including three concatenated AND logic gates or a 3-input OR logic gate. Biocatalytically produced NADH, controlled by various combinations of input signals, was used to activate the electrochemical system. A biocatalytic electrode associated with signal-processing "biocomputing" systems was electrically connected to another electrode coated with a polymer film, which was dissolved upon the formation of negative potential releasing entrapped drug-mimicking species, an enzyme-antibody conjugate, operating as a model for targeted immune-delivery and consequent "prodrug" activation. The system offers great versatility for future applications in controlled drug release and personalized medicine.

Selected luminal mucosal complications of adult celiac disease

OpenAIRE

Freeman, Hugh

2009-01-01

Hugh J FreemanDepartment of Medicine (Gastroenterology), University of British Columbia, Vancouver, BC, CanadaAbstract: Celiac disease is a gluten-dependent intestinal disorder that appears to be associated with several clinical conditions. Some involve the luminal mucosa of the stomach and intestinal tract and may, occasionally, complicate the course of celiac disease. Collagenous colitis has been associated with celiac disease and may lead to chronic diarrhea. Conversely, some of t...

The Dichotomous Cosmology with a Static Material World and Expanding Luminous World

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Heymann Y.

2014-07-01

Full Text Available The dichotomous cosmology is an alternative to the expanding Universe theory, and consists of a static matter Universe, where cosmological redshifts are explained by a tired-light model with an expanding luminous world. In this model the Hubble constant is also the photon energy decay rate, and the luminous world i s expanding at a constant rate as in de Sitter cosmology for an empty Universe. The present model explains both the luminosity distance versus redshift relationship of supernovae Ia, and ageing of spectra observed with the stretching of supernovae light curves. Furthermore, it is consistent with a radiation energy density factor (1 + z 4 inferred from the Cosmic Microwave Background Radiation.

Quantitative bronchial luminal volumetric assessment of pulmonary function loss by thin-section MDCT in pulmonary emphysema patients

International Nuclear Information System (INIS)

Koyama, Hisanobu; Ohno, Yoshiharu; Yamazaki, Youichi; Onishi, Yumiko; Takenaka, Daisuke; Yoshikawa, Takeshi; Nishio, Mizuho; Matsumoto, Sumiaki; Murase, Kenya; Nishimura, Yoshihiro; Sugimura, Kazuro

2012-01-01

Objectives: To determine the capability of quantitative bronchial luminal volume to assess pulmonary function loss and disease severity in pulmonary emphysema patients. Methods: Thirty-seven smokers (mean age, 68.1 years) underwent CT examinations and pulmonary function tests. For the quantitative assessment, luminal voxels of trachea and bronchi were computationally counted and the ratio of the following luminal voxels to all luminal voxels was obtained: (1) the lobe bronchi and the peripheral bronchi (Ratio lobe ), and (2) the main bronchi and the peripheral bronchi (Ratio main ). To determine the capability of these assessments to predict pulmonary function loss, these ratios were correlated with pulmonary function tests. To determine the capability for predicting disease severity, these ratios were compared between clinical groups. Results: These ratios were no significant correlated with vital capacity and forced vital capacity (FVC) (p > 0.05), however significantly correlated with forced expiratory volume in 1 s (FEV1) (Ratio lobe : r = 0.61, p main : r = 0.58, p lobe : r = 0.36, p main : r = 0.33, p lobe of smokers without COPD was significantly different from those of moderate COPD and severe or very severe COPD (p main of severe or very severe COPD patients was significantly different from those of other groups (p < 0.05). Conclusions: Quantitative bronchial luminal volumes were reflected the airflow limitation parameters and was corresponded to clinical groups in emphysema patients.

Might dark matter not be concentric with luminous matter

International Nuclear Information System (INIS)

Xu Chongming; Lu Tan.

1986-12-01

In this paper, an idea on dark matter nonconcentric with luminous matter is proposed. This case could influence the rotation curve of galaxy differently in its different direction. Recently, Rubin and Ford's observation on rotation curve of Hickson 88a has been explained by means of the idea. Some possible observational predictions have also been given. (author)

mTOR inhibitors, a new era for metastatic luminal HER2-negative breast cancer? A systematic review and a meta-analysis of randomized trials.

Science.gov (United States)

Rotundo, Maria Saveria; Galeano, Teresa; Tassone, Pierfrancesco; Tagliaferri, Pierosandro

2016-05-10

We evaluated if standard hormonal therapy (HT) could be improved by the addition of mammalian target of rapamycin inhibitors (mTOR-I) in metastatic luminal breast cancer. A meta-analysis on 4 phase II-III randomized clinical trials was performed. Pooled hazard ratio (HR) for progression free survival (PFS)/ time to progression (TTP) was 0.62 in favor of mTOR-I+HT arm (95% confidence interval [CI] 0.55-0.70; p<0.0001). There was significant heterogeneity for PFS/TTP (Cochran's Q 32, p<0.0001, I2 index 90.6%). Pooled HR for overall survival (OS) was 0.84 in favor of the combination arm (95% CI 0.71-0.99; p=0.04). Heterogeneity was not significant (Cochran's Q 4.47, p=0.1, I2 index 55.3%). Pooled risk ratio (RR) for objective response rate (ORR) was 0.88 in favor of experimental arm (95% CI 0.85-0.91; p<0.0001). Heterogeneity was not significant (Cochran's Q 2.11, p=0.3, I2 index 5.2%). Adverse events (AEs), in particular those of grade 3-4, mostly occurred in mTOR-I+HT arm. Combination therapy of HT plus mTOR-I improves the outcome of metastatic luminal breast cancer patients. Our results provide evidence of a class-effect of these targeting molecules.

Mechanical feedback in the molecular ISM of luminous IR galaxies

NARCIS (Netherlands)

Loenen, A. F.; Spaans, M.; Baan, W. A.; Meijerink, R.

Aims. Molecular emission lines originating in the nuclei of luminous infra-red galaxies are used to determine the physical properties of the nuclear ISM in these systems. Methods. A large observational database of molecular emission lines is compared with model predictions that include heating by UV

Nuclear and nucleolar localization signals and their targeting function in phosphatidylinositol 4-kinase PI4K230

International Nuclear Information System (INIS)

Kakuk, Annamaria; Friedlaender, Elza; Vereb, Gyoergy; Lisboa, Duarte; Bagossi, Peter; Toth, Gabor; Gergely, Pal; Vereb, Gyoergy

2008-01-01

PI4K230, an isoform of phosphatidylinositol 4-kinase, known primarily as a cytoplasmic membrane-bound enzyme, was detected recently also in the nucleolus of several cells. Here we provide mechanistic insight on the targeting function of its putative nuclear localization signal (NLS) sequences using molecular modeling, digitonin-permeabilized HeLa cells and binding to various importins. The synthetic sequence 916 NFNHIHKRIRRVADKYLSG 934 comprising a putative monopartite NLS (NLS1), targeted covalently bound fluorescent BSA to the nucleoplasm via classical importin α/β mechanism employing importins α1 and α3 but not α5. This transport was inhibited by wheat germ agglutinin and GTPγS. The sequence 1414 SKKTNRGSQLHKYYMKRRTL 1433 , a putative bipartite NLS (NLS2) proved ineffective in nuclear targeting if conjugated to fluorescently labeled BSA. Nonetheless, NLS2 or either of its basic clusters directed to the nucleolus soybean trypsin inhibitor that can pass the nuclear pore complex passively; moreover, an expressed 58 kDa fragment of PI4K230 (AA1166-1667) comprising NLS2 was also imported into the nucleus by import factors of reticulocyte lysate or by importin α1/β or α3/β complexes and localized to the nucleolus. We conclude that the putative bipartite NLS itself is a nucleolar targeting signal, and for nuclear import PI4K230 requires a larger sequence around it or, alternatively, the monopartite NLS

Chloroplasts as source and target of cellular redox regulation: a discussion on chloroplast redox signals in the context of plant physiology.

Science.gov (United States)

Baier, Margarete; Dietz, Karl-Josef

2005-06-01

During the evolution of plants, chloroplasts have lost the exclusive genetic control over redox regulation and antioxidant gene expression. Together with many other genes, all genes encoding antioxidant enzymes and enzymes involved in the biosynthesis of low molecular weight antioxidants were transferred to the nucleus. On the other hand, photosynthesis bears a high risk for photo-oxidative damage. Concomitantly, an intricate network for mutual regulation by anthero- and retrograde signals has emerged to co-ordinate the activities of the different genetic and metabolic compartments. A major focus of recent research in chloroplast regulation addressed the mechanisms of redox sensing and signal transmission, the identification of regulatory targets, and the understanding of adaptation mechanisms. In addition to redox signals communicated through signalling cascades also used in pathogen and wounding responses, specific chloroplast signals control nuclear gene expression. Signalling pathways are triggered by the redox state of the plastoquinone pool, the thioredoxin system, and the acceptor availability at photosystem I, in addition to control by oxolipins, tetrapyrroles, carbohydrates, and abscisic acid. The signalling function is discussed in the context of regulatory circuitries that control the expression of antioxidant enzymes and redox modulators, demonstrating the principal role of chloroplasts as the source and target of redox regulation.

Signal processing, sensor fusion, and target recognition; Proceedings of the Meeting, Orlando, FL, Apr. 20-22, 1992

Science.gov (United States)

Libby, Vibeke; Kadar, Ivan

Consideration is given to a multiordered mapping technique for target prioritization, a neural network approach to multiple-target-tracking problems, a multisensor fusion algorithm for multitarget multibackground classification, deconvolutiom of multiple images of the same object, neural networks and genetic algorithms for combinatorial optimization of sensor data fusion, classification of atmospheric acoustic signals from fixed-wing aircraft, and an optics approach to sensor fusion for target recognition. Also treated are a zoom lens for automatic target recognition, a hybrid model for the analysis of radar sensors, an innovative test bed for developing and assessing air-to-air noncooperative target identification algorithms, SAR imagery scene segmentation using fractal processing, sonar feature-based bandwidth compression, laboratory experiments for a new sonar system, computational algorithms for discrete transform using fixed-size filter matrices, and pattern recognition for power systems.

Grain formation in the expanding gas flow around cool luminous stars

International Nuclear Information System (INIS)

Hasegawa, H.

1984-01-01

The existence of solid particles in interstellar space has been revealed by the extinction of starlight in UV, visible and IR. The important sources of interstellar grains are considered to be cool luminous mass loss stars. (author)

Calcium reduces the sodium permeability of luminal membrane vesicles from toad bladder. Studies using a fast-reaction apparatus

International Nuclear Information System (INIS)

Chase, H.S. Jr.; Al-Awqati, Q.

1983-01-01

Regulation of the sodium permeability of the luminal membrane is the major mechanism by which the net rate of sodium transport across tight epithelia is varied. Previous evidence has suggested that the permeability of the luminal membrane might be regulated by changes in intracellular sodium or calcium activities. To test this directly, we isolated a fraction of the plasma membrane from the toad urinary bladder, which contains a fast, amiloride-sensitive sodium flux with characteristics similar to those of the native luminal membrane. Using a flow-quench apparatus to measure the initial rate of sodium efflux from these vesicles in the millisecond time range, we have demonstrated that the isotope exchange permeability of these vesicles is very sensitive to calcium. Calcium reduces the sodium permeability, and the half-maximal inhibitory concentration is 0.5 microM, well within the range of calcium activity found in cells. Also, the permeability of the luminal membrane vesicles is little affected by the ambient sodium concentration. These results, when taken together with studies on whole tissue, suggest that cell calcium may be an important regulator of transepithelial sodium transport by its effect on luminal sodium permeability. The effect of cell sodium on permeability may be mediated by calcium rather than by sodium itself

Surface regions of illusory images are detected with a slower processing speed than those of luminance-defined images.

Science.gov (United States)

Mihaylova, Milena; Manahilov, Velitchko

2010-11-24

Research has shown that the processing time for discriminating illusory contours is longer than for real contours. We know, however, little whether the visual processes, associated with detecting regions of illusory surfaces, are also slower as those responsible for detecting luminance-defined images. Using a speed-accuracy trade-off (SAT) procedure, we measured accuracy as a function of processing time for detecting illusory Kanizsa-type and luminance-defined squares embedded in 2D static luminance noise. The data revealed that the illusory images were detected at slower processing speed than the real images, while the points in time, when accuracy departed from chance, were not significantly different for both stimuli. The classification images for detecting illusory and real squares showed that observers employed similar detection strategies using surface regions of the real and illusory squares. The lack of significant differences between the x-intercepts of the SAT functions for illusory and luminance-modulated stimuli suggests that the detection of surface regions of both images could be based on activation of a single mechanism (the dorsal magnocellular visual pathway). The slower speed for detecting illusory images as compared to luminance-defined images could be attributed to slower processes of filling-in of regions of illusory images within the dorsal pathway.

Development and Application of a Microfluidics-Based Panel in the Basal/Luminal Transcriptional Characterization of Archival Bladder Cancers.

Directory of Open Access Journals (Sweden)

Doris Kim

Full Text Available In the age of personalized medicine stratifying tumors into molecularly defined subtypes associated with distinctive clinical behaviors and predictable responses to therapies holds tremendous value. Towards this end, we developed a custom microfluidics-based bladder cancer gene expression panel for characterization of archival clinical samples. In silico analysis indicated that the content of our panel was capable of accurately segregating bladder cancers from several public datasets into the clinically relevant basal and luminal subtypes. On a technical level, our bladder cancer panel yielded robust and reproducible results when analyzing formalin-fixed, paraffin-embedded (FFPE tissues. We applied our panel in the analysis of a novel set of 204 FFPE samples that included non-muscle invasive bladder cancers (NMIBCs, muscle invasive disease (MIBCs, and bladder cancer metastases (METs. We found NMIBCs to be mostly luminal-like, MIBCs to include both luminal- and basal-like types, and METs to be predominantly of a basal-like transcriptional profile. Mutational analysis confirmed the expected enrichment of FGFR3 mutations in luminal samples, and, consistently, FGFR3 IHC showed high protein expression levels of the receptor in these tumors. Our bladder cancer panel enables basal/luminal characterization of FFPE tissues and with further development could be used for stratification of bladder cancer samples in the clinic.

PALBOCICLIB IN COMBINATION WITH HORMONE THERAPY FOR LUMINAL HER2-NEGATIVE METASTATIC BREAST CANCER: NEW HIGHLY EFFECTIVE STRATEGY OF DRUG TREATMENT

Directory of Open Access Journals (Sweden)

E. V. Artamonova

2017-01-01

Full Text Available The review considers a new oral targeted drug palbociclib and its place in treatment of luminal (estrogen receptor-positive HER2– metastatic breast cancer. The results of randomized clinical trials have shown that inclusion of palbociclib in various hormone therapy regimens for treatment of HER2– metastatic breast cancer with expression of estrogen receptors allows to significantly improve clinical outcomes and increase survival, objective response rate and its duration, as well as clinical benefit rate (CBR. Addition of palbociclib to letrozole in the 1st line hormone therapy or to fulvestrant in patients with progression at/after previous endocrine therapy increased progression-free survival in all groups irrespective of clinical characteristics, tumor progression, or expression of molecular markers mediating development of hormone resistance. The main adverse events associated with palbociclib were neutropenia, leukopenia and thrombocytopenia, but overall hematological toxicity was manageable, and the therapy itself was safe. This strategy received a “breakthrough therapy designation” from the experts and combines proven effectiveness and satisfactory tolerability, allows to maintain high quality of life, and should be prescribed to patients with luminal HER2– metastatic breast cancer.

Molecular Pathways: Cachexia Signaling-A Targeted Approach to Cancer Treatment.

Science.gov (United States)

Miyamoto, Yuji; Hanna, Diana L; Zhang, Wu; Baba, Hideo; Lenz, Heinz-Josef

2016-08-15

Cancer cachexia is a multifactorial syndrome characterized by an ongoing loss of skeletal muscle mass, which negatively affects quality of life and portends a poor prognosis. Numerous molecular substrates and mechanisms underlie the dysregulation of skeletal muscle synthesis and degradation observed in cancer cachexia, including proinflammatory cytokines (TNFα, IL1, and IL6), and the NF-κB, IGF1/AKT/mTOR, and myostatin/activin-SMAD pathways. Recent preclinical and clinical studies have demonstrated that anti-cachexia drugs (such as MABp1 and soluble receptor antagonist of myostatin/activin) not only prevent muscle wasting but also may prolong overall survival. In this review, we focus on the significance of cachexia signaling in patients with cancer and highlight promising drugs targeting tumor cachexia in clinical development. Clin Cancer Res; 22(16); 3999-4004. ©2016 AACR. ©2016 American Association for Cancer Research.

Underlying mechanisms of transient luminous events: a review

OpenAIRE

V. V. Surkov; M. Hayakawa

2012-01-01

Transient luminous events (TLEs) occasionally observed above a strong thunderstorm system have been the subject of a great deal of research during recent years. The main goal of this review is to introduce readers to recent theories of electrodynamics processes associated with TLEs. We examine the simplest versions of these theories in order to make their physics as transparent as possible. The study is begun with the conventional mechanism for air breakdown at stratospheric...

Effects of feeding on luminal pH and morphology of the gastroesophageal junction of snakes.

Science.gov (United States)

Bessler, Scott M; Secor, Stephen M

2012-10-01

At the gastroesophageal junction, most vertebrates possess a functional lower esophageal sphincter (LES) which may serve to regulate the passage of liquids and food into the stomach and prevent the reflux of gastric contents into the esophagus. Snakes seemingly lack an LES and consume meals large enough to extend anteriorly from the stomach into the esophagus thereby providing the opportunity for the reflux of gastric juices. To explore whether snakes experience or can prevent gastric reflux, we examined post-feeding changes of luminal pH of the distal esophagus and stomach, the fine scale luminal pH profile at the gastroesophageal junction, and the morphology of the gastroesophageal junction for the Burmese python (Python molurus), the African brown house snake (Lamprophis fuliginosus), and the diamondback water snake (Nerodia rhombifer). For each species fasted, there was no distension of the gastroesophageal junction and only modest changes in luminal pH from the distal esophagus into the stomach. Feeding resulted in marked distension and changes in tissue morphology of the gastroesophageal junction. Simultaneously, there was a significant decrease in luminal pH of the distal esophagus for pythons and house snakes, and for all three species a steep gradient in luminal pH decreasing across a 3-cm span from the distal edge of the esophagus into the proximal edge of the stomach. The moderate acidification of the distal most portion of the esophagus for pythons and house snakes suggests that there is some anterior movement of gastric juices across the gastroesophageal junction. Given that this modest reflux of gastric fluid is localized to the most distal region of the esophagus, snakes are apparently able to prevent and protect against acid reflux in the absence of a functional LES. Copyright © 2012 Elsevier GmbH. All rights reserved.

Sphingosine-1-Phosphate (S1P) and S1P Signaling Pathway: Therapeutic Targets in Autoimmunity and Inflammation.

Science.gov (United States)

Tsai, Hsing-Chuan; Han, May H

2016-07-01

Sphingosine-1-phosphate (S1P) and S1P receptors (S1PR) are ubiquitously expressed. S1P-S1PR signaling has been well characterized in immune trafficking and activation in innate and adaptive immune systems. However, the full extent of its involvement in the pathogenesis of autoimmune diseases is not well understood. FTY720 (fingolimod), a non-selective S1PR modulator, significantly decreased annualized relapse rates in relapsing-remitting multiple sclerosis (MS). FTY720, which primarily targets S1P receptor 1 as a functional antagonist, arrests lymphocyte egress from secondary lymphoid tissues and reduces neuroinflammation in the central nervous system (CNS). Recent studies suggest that FTY720 also decreases astrogliosis and promotes oligodendrocyte differentiation within the CNS and may have therapeutic benefit to prevent brain atrophy. Since S1P signaling is involved in multiple immune functions, therapies targeting S1P axis may be applicable to treat autoimmune diseases other than MS. Currently, over a dozen selective S1PR and S1P pathway modulators with potentially superior therapeutic efficacy and better side-effect profiles are in the pipeline of drug development. Furthermore, newly characterized molecules such as apolipoprotein M (ApoM) (S1P chaperon) and SPNS2 (S1P transporter) are also potential targets for treatment of autoimmune diseases. Finally, the application of therapies targeting S1P and S1P signaling pathways may be expanded to treat several other immune-mediated disorders (such as post-infectious diseases, post-stroke and post-stroke dementia) and inflammatory conditions beyond their application in primary autoimmune diseases.

Radiation properties of two types of luminous textile devices containing plastic optical fibers

Science.gov (United States)

Selm, Bärbel; Rothmaier, Markus

2007-05-01

Luminous textiles have the potential to satisfy a need for thin and flexible light diffusers for treatment of intraoral cancerous tissue. Plastic optical fibers (POF) with diameters of 250 microns and smaller are used to make the textiles luminous. Usually light is supplied to the optical fiber at both ends. On the textile surface light emission occurs in a woven structure via damaged straight POFs, whereas the embroidered structure radiates the light out of macroscopically bent POFs. We compared the optical properties of these two types of textile diffusers using red light laser for the embroidery and light emitting diode (LED) for the woven structure as light sources, and found efficiencies for the luminous areas of the two samples of 19 % (woven) and 32 % (embroidery), respectively. It was shown that the efficiency can be greatly improved using an aluminium backing. Additional scattering layers lower the fluence rate by around 30 %. To analyse the homogeneity we took a photo of the illuminated surface using a 3CCD camera and found, for both textiles, a slightly skewed distribution of the dark and bright pixels. The interquartile range of brightness distribution of the embroidery is more than double as the woven structure.

Clustering Batik Images using Fuzzy C-Means Algorithm Based on Log-Average Luminance

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Ahmad Sanmorino

2012-06-01

Full Text Available Batik is a fabric or clothes that are made ​​with a special staining technique called wax-resist dyeing and is one of the cultural heritage which has high artistic value. In order to improve the efficiency and give better semantic to the image, some researchers apply clustering algorithm for managing images before they can be retrieved. Image clustering is a process of grouping images based on their similarity. In this paper we attempt to provide an alternative method of grouping batik image using fuzzy c-means (FCM algorithm based on log-average luminance of the batik. FCM clustering algorithm is an algorithm that works using fuzzy models that allow all data from all cluster members are formed with different degrees of membership between 0 and 1. Log-average luminance (LAL is the average value of the lighting in an image. We can compare different image lighting from one image to another using LAL. From the experiments that have been made, it can be concluded that fuzzy c-means algorithm can be used for batik image clustering based on log-average luminance of each image possessed.

Sonic Hedgehog Signaling Drives Proliferation of Synoviocytes in Rheumatoid Arthritis: A Possible Novel Therapeutic Target

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Mingxia Wang

2014-01-01

Full Text Available Sonic hedgehog (Shh signaling controls many aspects of human development, regulates cell growth and differentiation in adult tissues, and is activated in a number of malignancies. Rheumatoid arthritis (RA is characterized by chronic synovitis and pannus formation associated with activation of fibroblast-like synoviocytes (FLS. We investigated whether Shh signaling plays a role in the proliferation of FLS in RA. Expression of Shh signaling related components (Shh, Ptch1, Smo, and Gli1 in RA synovial tissues was examined by immunohistochemistry (IHC and in FLS by IHC, immunofluorescence (IF, quantitative RT-PCR, and western blotting. Expression of Shh, Smo, and Gli1 in RA synovial tissue was higher than that in control tissue (P<0.05. Cyclopamine (a specific inhibitor of Shh signaling decreased mRNA expression of Shh, Ptch1, Smo, and Gli1 in cultured RA FLS, Shh, and Smo protein expression, and significantly decreased FLS proliferation. Flow cytometry analysis suggested that cyclopamine treatment resulted in cell cycle arrest of FLS in G1 phase. Our data show that Shh signaling is activated in synovium of RA patients in vivo and in cultured FLS form RA patients in vitro, suggesting a role in the proliferation of FLS in RA. It may therefore be a novel therapeutic target in RA.

Increasing the luminous efficiency of an MEH-PPV based PLED using salmon DNA and single walled carbon nanotube

International Nuclear Information System (INIS)

Madhwal, Devinder; Singh, Inderpreet; Kumar, Jitender; Bhatia, C.S.; Bhatnagar, P.K.; Mathur, P.C.

2011-01-01

The combined effect of a salmon deoxyribonucleic acid (DNA)-based electron blocking layer and a single walled carbon nanotube (SWCNT) composite-based electron transport layer on the performance of a poly[2-methoxy-5-(2'-ethyl-hexyloxy)-1,4-phenylene vinylene] (MEH-PPV) polymer light emitting diode (PLED) has been examined. The SWCNT network in the composite layer improves electron injection from cathode and the DNA blocks these high mobility electrons at the electron blocking layer-polymer interface, leading to high luminance from the device. The luminous efficiency of the PLED is increased ∼20 times compared to that of a PLED using only MEH-PPV. - Highlights: → We report fabrication of a high luminous efficiency MEH-PPV based polymer LED. → Salmon DNA-CTMA layer is used to block injected electrons in the polymer layer. → MEH-PPV-SWCNT composite is used to transport electrons in the polymer layer. → The luminous efficiency of the polymer LED thereby improves about 20 times.

Enigmatic sub-luminous accreting neutron stars in our Galaxy

NARCIS (Netherlands)

Wijnands, R.

2008-01-01

During the last few years a class of enigmatic sub-luminous accreting neutron stars has been found in our Galaxy. They have peak X-ray luminosities (2-10 keV) of a few times 10(34) erg s(−1) to a few times 10(35) erg s(−1), and both persistent and transient sources have been found. I present a short

Automatic Supervision of Temperature, Humidity, and Luminance with an Assistant Personal Robot

Directory of Open Access Journals (Sweden)

Jordi Palacín

2017-01-01

Full Text Available Smart environments and Ambient Intelligence (AmI technologies are defining the future society where energy optimization and intelligent management are essential for a sustainable advance. Mobile robotics is also making an important contribution to this advance with the integration of sensors and intelligent processing algorithms. This paper presents the application of an Assistant Personal Robot (APR as an autonomous agent for temperature, humidity, and luminance supervision in human-frequented areas. The robot multiagent capabilities allow gathering sensor information while exploring or performing specific tasks and then verifying human comfortability levels. The proposed methodology creates information maps with the distribution of temperature, humidity, and luminance and interprets such information in terms of comfort and warns about corrective actuations if required.

REVIEW ARTICLE: Bioluminescent signals and the role of reflectors

Science.gov (United States)

Herring, Peter J.

2000-11-01

Organisms in a well lit environment use optical signals derived from the selective reflection of ambient light. In a dim or dark environment it is very difficult (because of low photon numbers) to detect the contrast between light reflected from the organism and that from the background, and many organisms use bioluminescent signals instead. The use of such signals on land is largely restricted to sexual signalling by the luminous beetles, but in the deep ocean their use is widespread, involving both many different organisms and a range of uses which parallel those of reflective signals on land. Some bioluminescent signals rely almost entirely on an optically unmodified light source (e.g. a secretion) but others depend upon complex optical structures, particularly reflectors, in the light-emitting organs. Reflectors in the light organs of many shrimp, squid and fish are based on constructive interference systems but employ different biological materials. They and other structures modify the angular, spectral and intensity distributions of bioluminescent signals. The ready availability of highly efficient biological reflectors has been a formative influence in the evolution of bioluminescent signalling in the sea.

Discovery of a Novel Inhibitor of the Hedgehog Signaling Pathway through Cell-based Compound Discovery and Target Prediction.

Science.gov (United States)

Kremer, Lea; Schultz-Fademrecht, Carsten; Baumann, Matthias; Habenberger, Peter; Choidas, Axel; Klebl, Bert; Kordes, Susanne; Schöler, Hans R; Sterneckert, Jared; Ziegler, Slava; Schneider, Gisbert; Waldmann, Herbert

2017-10-09

Cell-based assays enable monitoring of small-molecule bioactivity in a target-agnostic manner and help uncover new biological mechanisms. Subsequent identification and validation of the small-molecule targets, typically employing proteomics techniques, is very challenging and limited, in particular if the targets are membrane proteins. Herein, we demonstrate that the combination of cell-based bioactive-compound discovery with cheminformatic target prediction may provide an efficient approach to accelerate the process and render target identification and validation more efficient. Using a cell-based assay, we identified the pyrazolo-imidazole smoothib as a new inhibitor of hedgehog (Hh) signaling and an antagonist of the protein smoothened (SMO) with a novel chemotype. Smoothib targets the heptahelical bundle of SMO, prevents its ciliary localization, reduces the expression of Hh target genes, and suppresses the growth of Ptch +/- medulloblastoma cells. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Visceral Crisis Means Short Survival Among Patients With Luminal A Metastatic Breast Cancer: A Retrospective Cohort Study.

Science.gov (United States)

Sbitti, Yassir; Slimani, Khaoula; Debbagh, Adil; Mokhlis, Anouar; Kadiri, Habiba; Laraqui, Abdelilah; Errihani, Hassan; Ichou, Mohamed

2017-08-01

Patients with visceral crisis from luminal metastatic breast cancer (mBC) are often treated with palliative chemotherapy. No studies have analyzed the aggressiveness of the care in visceral crisis from luminal mBC patients. The objective of this study was to assess practices in this setting in a university medical oncology department. This retrospective study included all patients who were managed for luminal mBC between January 2013 and April 2016. The analysis focused on the characteristics of the patients, the modalities of cancer treatment and delays between visceral crisis and death. Thirty-five patients pre-treated with two hormonal therapy lines were enrolled retrospectively. Worse performance status and a higher proportion of severe organ dysfunction for luminal mBC were observed among patients with visceral crisis. Sixty-five percent of patients received cytotoxic treatment. One cycle of chemotherapy was administrated in the majority of patients. Palliative care was performed in 35% of patients. Chemotherapy did not have any significant effect on patient outcome in the present study. The mean time between visceral crisis and death was 4.7 weeks (standard deviation = 1.9). Our study showed that visceral crisis in patients with luminal mBC is a complex problem. We need more comprehension of molecular pathogenesis to visceral crisis disease to propose efficacious treatments for these patients and to identify subgroup of patients who need chemotherapy followed by maintenance endocrine therapy.

Green tea polyphenol, (−)-epigallocatechin-3-gallate, induces toxicity in human skin cancer cells by targeting β-catenin signaling

Energy Technology Data Exchange (ETDEWEB)

Singh, Tripti [Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL 35294 (United States); Katiyar, Santosh K., E-mail: skatiyar@uab.edu [Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL 35294 (United States); Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL 35294 (United States); Birmingham Veterans Affairs Medical Center, Birmingham, AL 35233 (United States)

2013-12-01

The green tea polyphenol, (−)-epigallocatechin-3-gallate (EGCG), has been shown to have anti-carcinogenic effects in several skin tumor models, and efforts are continued to investigate the molecular targets responsible for its cytotoxic effects to cancer cells. Our recent observation that β-catenin is upregulated in skin tumors suggested the possibility that the anti-skin carcinogenic effects of EGCG are mediated, at least in part, through its effects on β-catenin signaling. We have found that treatment of the A431 and SCC13 human skin cancer cell lines with EGCG resulted in reduced cell viability and increased cell death and that these cytotoxic effects were associated with inactivation of β-catenin signaling. Evidence of EGCG-induced inactivation of β-catenin included: (i) reduced accumulation of nuclear β-catenin; (ii) enhanced levels of casein kinase1α, reduced phosphorylation of glycogen synthase kinase-3β, and increased phosphorylation of β-catenin on critical serine{sup 45,33/37} residues; and (iii) reduced levels of matrix metalloproteinase (MMP)-2 and MMP-9, which are down-stream targets of β-catenin. Treatment of cells with prostaglandin E2 (PGE{sub 2}) enhanced the accumulation of β-catenin and enhanced β-catenin signaling. Treatment with either EGCG or an EP2 antagonist (AH6809) reduced the PGE{sub 2}-enhanced levels of cAMP, an upstream regulator of β-catenin. Inactivation of β-catenin by EGCG resulted in suppression of cell survival signaling proteins. siRNA knockdown of β-catenin in A431 and SCC13 cells reduced cell viability. Collectively, these data suggest that induction of cytotoxicity in skin cancer cells by EGCG is mediated by targeting of β-catenin signaling and that the β-catenin signaling is upregulated by inflammatory mediators. - Highlights: • EGCG inhibits cancer cell viability through inactivation of β-catenin signaling. • Inactivation of β-catenin involves the downregulation of inflammatory mediators. • EGCG

PAX2 is activated by estradiol in breast cancer cells of the luminal subgroup selectively, to confer a low invasive phenotype

Science.gov (United States)

2011-01-01

Background Metastasis is the leading cause of death among breast cancer patients. Identifying key cellular factors controlling invasion and metastasis of breast cancer cells should pave the way to new therapeutic strategies efficiently interfering with the metastatic process. PAX2 (paired box 2) transcription factor is expressed by breast cancer cells in vivo and recently, it was shown to negatively regulate the expression of ERBB2 (erythroblastic leukemia viral oncogene homolog 2, HER-2/neu), a well-documented pro-invasive and pro-metastastic gene, in luminal/ERalpha-positive (ERα+) breast cancer cells. The objective of the present study was to investigate a putative role for PAX2 in the control of luminal breast cancer cells invasion, and to begin to characterize its regulation. Results PAX2 activity was higher in cell lines from luminal compared to non-luminal subtype, and activation of PAX2 by estradiol was selectively achieved in breast cancer cell lines of the luminal subtype. This process was blocked by ICI 182780 and could be antagonized by IGF-1. Knockdown of PAX2 in luminal MCF-7 cells completely abrogated estradiol-induced downregulation of ERBB2 and decrease of cell invasion, whereas overexpression of PAX2 in these cells enhanced estradiol effects on ERBB2 levels and cell invasion. Conclusions The study demonstrates that PAX2 activation by estradiol is selectively achieved in breast cancer cells of the luminal subtype, via ERα, and identifies IGF-1 as a negative regulator of PAX2 activity in these cells. Further, it reveals a new role for PAX2 in the maintenance of a low invasive behavior in luminal breast cancer cells upon exposure to estradiol, and shows that overexpression and activation of PAX2 in these cells is sufficient to reduce their invasive ability. PMID:22168360

Modeling ductal carcinoma in situ: a HER2-Notch3 collaboration enables luminal filling.

LENUS (Irish Health Repository)

Pradeep, C-R

2012-02-16

A large fraction of ductal carcinoma in situ (DCIS), a non-invasive precursor lesion of invasive breast cancer, overexpresses the HER2\\/neu oncogene. The ducts of DCIS are abnormally filled with cells that evade apoptosis, but the underlying mechanisms remain incompletely understood. We overexpressed HER2 in mammary epithelial cells and observed growth factor-independent proliferation. When grown in extracellular matrix as three-dimensional spheroids, control cells developed a hollow lumen, but HER2-overexpressing cells populated the lumen by evading apoptosis. We demonstrate that HER2 overexpression in this cellular model of DCIS drives transcriptional upregulation of multiple components of the Notch survival pathway. Importantly, luminal filling required upregulation of a signaling pathway comprising Notch3, its cleaved intracellular domain and the transcriptional regulator HES1, resulting in elevated levels of c-MYC and cyclin D1. In line with HER2-Notch3 collaboration, drugs intercepting either arm reverted the DCIS-like phenotype. In addition, we report upregulation of Notch3 in hyperplastic lesions of HER2 transgenic animals, as well as an association between HER2 levels and expression levels of components of the Notch pathway in tumor specimens of breast cancer patients. Therefore, it is conceivable that the integration of the Notch and HER2 signaling pathways contributes to the pathophysiology of DCIS.

Inhibitors of acid secretion can benefit gastric wound repair independent of luminal pH effects on the site of damage

Science.gov (United States)

Demitrack, Elise S; Aihara, Eitaro; Kenny, Susan; Varro, Andrea; Montrose, Marshall H

2012-01-01

Background and aims The authors’ goal was to measure pH at the gastric surface (pHo) to understand how acid secretion affects the repair of microscopic injury to the gastric epithelium. Methods Microscopic gastric damage was induced by laser light, during confocal/two-photon imaging of pH-sensitive dyes (Cl-NERF, BCECF) that were superfused over the mucosal surface of the exposed gastric corpus of anaesthetised mice. The progression of repair was measured in parallel with pHo. Experimental conditions included varying pH of luminal superfusates, and using omeprazole (60 mg/kg ip) or famotidine (30 mg/kg ip) to inhibit acid secretion. Results Similar rates of epithelial repair and resting pHo values (~pH 4) were reported in the presence of luminal pH 3 or pH 5. Epithelial repair was unreliable at luminal pH 2 and pHo was lower (2.5±0.2, P pH 3). Epithelial repair was slower at luminal pH 7 and pHo was higher (6.4±0.1, PpH 3 or pH 7, omeprazole reduced maximal damage size and accelerated epithelial repair, although only at pH 3 did omeprazole further increase surface pH above the level caused by imposed damage. At luminal pH 7, famotidine also reduced maximal damage size and accelerated epithelial repair. Neither famotidine nor omeprazole raised plasma gastrin levels during the time course of the experiments. Conclusions Epithelial repair in vivo is affected by luminal pH variation, but the beneficial effects of acutely blocking acid secretion extend beyond simply raising luminal and/or surface pH. PMID:21997560

SI 1985 No. 1048 - The Radioactive Substances (Luminous Articles) Exemption Order 1985

International Nuclear Information System (INIS)

1985-01-01

This Order, which came into force on 17 September 1985, is concerned with exemptions and exclusions under the Radioactive Substances Act 1960 in respect of radioactive luminous instruments and indicators. (NEA) [fr

Luminal digestion of lactoferrin in suckling and weanling rats

International Nuclear Information System (INIS)

Britton, J.R.; Koldovsky, O.

1987-01-01

The development of luminal digestion of lactoferrin was evaluated in vitro by incubating 125 I-labeled lactoferrin with fluid flushed from the stomach and small intestine of 12-day-old suckling and 31-day-old weanling rats, followed by measurement of radioactivity in trichloroacetic acid-soluble material. Gastric hydrolysis of lactoferrin at pH 3.2 in the weanling was 20-fold greater than that in the suckling. In the small intestine at neutral pH, luminal degradation of lactoferrin was minimal in the suckling but increased significantly after weaning, with maximal degradative capacity demonstrable in the midjejunum. Sephadex G-75 chromatography of intestinal acid-soluble breakdown products revealed two peaks of radioactivity, each comprising 40-45% of the total product; analysis of intestinal acid-precipitable products by polyacrylamide gel electrophoresis yielded several discrete lower molecular weight species. Food deprivation for 12 h/100 g body wt decreased lactoferrin degradation in the weanling jejunum and midjejunum. The findings suggest that lactoferrin digestion may vary with respect to postnatal age of the organism, segment of the gastrointestinal tract, and dietary state. In the young animal, lactoferrin degradation is minimal, and consequently its potential for biological function may be high

Targeting cytokine signaling checkpoint CIS activates NK cells to protect from tumor initiation and metastasis

Science.gov (United States)

Putz, Eva M.; Guillerey, Camille; Kos, Kevin; Stannard, Kimberley; Miles, Kim; Delconte, Rebecca B.; Nicholson, Sandra E.; Huntington, Nicholas D.; Smyth, Mark J.

2017-01-01

ABSTRACT The cytokine-induced SH2-containing protein CIS belongs to the suppressor of cytokine signaling (SOCS) protein family. Here, we show the critical role of CIS in suppressing natural killer (NK) cell control of tumor initiation and metastasis. Cish-deficient mice were highly resistant to methylcholanthrene-induced sarcoma formation and protected from lung metastasis of B16F10 melanoma and RM-1 prostate carcinoma cells. In contrast, the growth of primary subcutaneous tumors, including those expressing the foreign antigen OVA, was unchanged in Cish-deficient mice. The combination of Cish deficiency and relevant targeted and immuno-therapies such as combined BRAF and MEK inhibitors, immune checkpoint blockade antibodies, IL-2 and type I interferon revealed further improved control of metastasis. The data clearly indicate that targeting CIS promotes NK cell antitumor functions and CIS holds great promise as a novel target in NK cell immunotherapy. PMID:28344878

Peroxisome Proliferator-Activated Receptor-γ Ligands: Potential Pharmacological Agents for Targeting the Angiogenesis Signaling Cascade in Cancer

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Costas Giaginis

2008-01-01

Full Text Available Peroxisome proliferator-activated receptor-γ (PPAR-γ has currently been considered as molecular target for the treatment of human metabolic disorders. Experimental data from in vitro cultures, animal models, and clinical trials have shown that PPAR-γ ligand activation regulates differentiation and induces cell growth arrest and apoptosis in a variety of cancer types. Tumor angiogenesis constitutes a multifaceted process implicated in complex downstream signaling pathways that triggers tumor growth, invasion, and metastasis. In this aspect, accumulating in vitro and in vivo studies have provided extensive evidence that PPAR-γ ligands can function as modulators of the angiogenic signaling cascade. In the current review, the crucial role of PPAR-γ ligands and the underlying mechanisms participating in tumor angiogenesis are summarized. Targeting PPAR-γ may prove to be a potential therapeutic strategy in combined treatments with conventional chemotherapy; however, special attention should be taken as there is also substantial evidence to support that PPAR-γ ligands can enhance angiogenic phenotype in tumoral cells.

Romidepsin targets multiple survival signaling pathways in malignant T cells

International Nuclear Information System (INIS)

Valdez, B C; Brammer, J E; Li, Y; Murray, D; Liu, Y; Hosing, C; Nieto, Y; Champlin, R E; Andersson, B S

2015-01-01

Romidepsin is a cyclic molecule that inhibits histone deacetylases. It is Food and Drug Administration-approved for treatment of cutaneous and peripheral T-cell lymphoma, but its precise mechanism of action against malignant T cells is unknown. To better understand the biological effects of romidepsin in these cells, we exposed PEER and SUPT1 T-cell lines, and a primary sample from T-cell lymphoma patient (Patient J) to romidepsin. We then examined the consequences in some key oncogenic signaling pathways. Romidepsin displayed IC 50 values of 10.8, 7.9 and 7.0 nm in PEER, SUPT1 and Patient J cells, respectively. Strong inhibition of histone deacetylases and demethylases, increased production of reactive oxygen species and decreased mitochondrial membrane potential were observed, which may contribute to the observed DNA-damage response and apoptosis. The stress-activated protein kinase/c-Jun N-terminal kinase signaling pathway and unfolded protein response in the endoplasmic reticulum were activated, whereas the phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin (PI3K/AKT/mTOR) and β-catenin pro-survival pathways were inhibited. The decreased level of β-catenin correlated with the upregulation of its inhibitor SFRP1 through romidepsin-mediated hypomethylation of its gene promoter. Our results provide new insights into how romidepsin invokes malignant T-cell killing, show evidence of its associated DNA hypomethylating activity and offer a rationale for the development of romidepsin-containing combination therapies

Gastric luminal epidermal growth factor is affected by diet | Iputo ...

African Journals Online (AJOL)

Objective. Diet is an area of major interest to those investigating the causes of cancer of the oesophagus in the Transkei. This study looked at the associations between intragastric epidermal growth factor level, diet and intragastric pH. Setting and subjects. A dietary survey was co-ordinated with studies of gastric luminal ...

The predetermination of the luminance in tunnel entrances at day.

NARCIS (Netherlands)

Schreuder, D.A. & Oud, H.J.C.

1988-01-01

In tunnel lighting practice, only the scatter in the eye, in the windscreen of the car, and in the atmosphere need to be taken into account. For all practical day- time conditions, the required luminance in any portion of the tunnel can be assessed as being a constant fraction of this sum-

Immunoelectron microscopic localisation of keratin and luminal epithelial antigens in normal and neoplastic urothelium.

Science.gov (United States)

Wilson, P D; Nathrath, W B; Trejdosiewicz, L K

1982-01-01

Immunoelectron microscope cytochemistry was carried out on 2% paraformaldehyde fixed, 50 mu sections of normal urothelium and bladder carcinoma cells in culture using antisera raised in rabbits to human 40-63 000 MW epidermal "broad spectrum" keratin and calf urothelial "luminal epithelial antigen" (aLEA) Both the unconjugated and indirect immunoperoxidase-DAB techniques were used before routine embedding. The localisation of both keratin and luminal epithelial antigen (LEA) was similar in normal and neoplastic cells and reaction product was associated not only with tonofilaments but also lining membrane vesicles and on fine filaments in the cytoplasmic ground substance.

Assessment of atherosclerotic luminal narrowing of coronary arteries based on morphometrically generated visual guides.

Science.gov (United States)

Barth, Rolf F; Kellough, David A; Allenby, Patricia; Blower, Luke E; Hammond, Scott H; Allenby, Greg M; Buja, L Maximilian

Determination of the degree of stenosis of atherosclerotic coronary arteries is an important part of postmortem examination of the heart, but, unfortunately, estimation of the degree of luminal narrowing can be imprecise and tends to be approximations. Visual guides can be useful to assess this, but earlier attempts to develop such guides did not employ digital technology. Using this approach, we have developed two computer-generated morphometric guides to estimate the degree of luminal narrowing of atherosclerotic coronary arteries. The first is based on symmetric or eccentric circular or crescentic narrowing of the vessel lumen and the second on either slit-like or irregularly shaped narrowing of the vessel lumens. Using the Aperio ScanScope XT at a magnification of 20× we created digital whole-slide images of 20 representative microscopic cross sections of the left anterior descending (LAD) coronary artery, stained with either hematoxylin and eosin (H&E) or Movat's pentachrome stain. These cross sections illustrated a variety of luminal profiles and degrees of stenosis. Three representative types of images were selected and a visual guide was constructed with Adobe Photoshop CS5. Using the "Scale" and "Measurement" tools, we created a series of representations of stenosis with luminal cross sections depicting 20%, 40%, 60%, 70%, 80%, and 90% occlusion of the LAD branch. Four pathologists independently reviewed and scored the degree of atherosclerotic luminal narrowing based on our visual guides. In addition, digital technology was employed to determine the degree of narrowing by measuring the cross-sectional area of the 20 microscopic sections of the vessels, first assuming no narrowing and then comparing this to the percent of narrowing determined by precise measurement. Two of the observers were very experienced general autopsy pathologists, one was a first-year pathology resident on his first rotation on the autopsy service, and the fourth observer was a

Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies

Science.gov (United States)

Lehmann, Brian D.; Bauer, Joshua A.; Chen, Xi; Sanders, Melinda E.; Chakravarthy, A. Bapsi; Shyr, Yu; Pietenpol, Jennifer A.

2011-01-01

Triple-negative breast cancer (TNBC) is a highly diverse group of cancers, and subtyping is necessary to better identify molecular-based therapies. In this study, we analyzed gene expression (GE) profiles from 21 breast cancer data sets and identified 587 TNBC cases. Cluster analysis identified 6 TNBC subtypes displaying unique GE and ontologies, including 2 basal-like (BL1 and BL2), an immunomodulatory (IM), a mesenchymal (M), a mesenchymal stem–like (MSL), and a luminal androgen receptor (LAR) subtype. Further, GE analysis allowed us to identify TNBC cell line models representative of these subtypes. Predicted “driver” signaling pathways were pharmacologically targeted in these cell line models as proof of concept that analysis of distinct GE signatures can inform therapy selection. BL1 and BL2 subtypes had higher expression of cell cycle and DNA damage response genes, and representative cell lines preferentially responded to cisplatin. M and MSL subtypes were enriched in GE for epithelial-mesenchymal transition, and growth factor pathways and cell models responded to NVP-BEZ235 (a PI3K/mTOR inhibitor) and dasatinib (an abl/src inhibitor). The LAR subtype includes patients with decreased relapse-free survival and was characterized by androgen receptor (AR) signaling. LAR cell lines were uniquely sensitive to bicalutamide (an AR antagonist). These data may be useful in biomarker selection, drug discovery, and clinical trial design that will enable alignment of TNBC patients to appropriate targeted therapies. PMID:21633166

Targeting p53 via JNK pathway: a novel role of RITA for apoptotic signaling in multiple myeloma.

Science.gov (United States)

Saha, Manujendra N; Jiang, Hua; Yang, Yijun; Zhu, Xiaoyun; Wang, Xiaoming; Schimmer, Aaron D; Qiu, Lugui; Chang, Hong

2012-01-01

The low frequency of p53 alterations e.g., mutations/deletions (∼10%) in multiple myeloma (MM) makes this tumor type an ideal candidate for p53-targeted therapies. RITA is a small molecule which can induce apoptosis in tumor cells by activating the p53 pathway. We previously showed that RITA strongly activates p53 while selectively inhibiting growth of MM cells without inducing genotoxicity, indicating its potential as a drug lead for p53-targeted therapy in MM. However, the molecular mechanisms underlying the pro-apoptotic effect of RITA are largely undefined. Gene expression analysis by microarray identified a significant number of differentially expressed genes associated with stress response including c-Jun N-terminal kinase (JNK) signaling pathway. By Western blot analysis we further confirmed that RITA induced activation of p53 in conjunction with up-regulation of phosphorylated ASK-1, MKK-4 and c-Jun. These results suggest that RITA induced the activation of JNK signaling. Chromatin immunoprecipitation (ChIP) analysis showed that activated c-Jun binds to the activator protein-1 (AP-1) binding site of the p53 promoter region. Disruption of the JNK signal pathway by small interfering RNA (siRNA) against JNK or JNK specific inhibitor, SP-600125 inhibited the activation of p53 and attenuated apoptosis induced by RITA in myeloma cells carrying wild type p53. On the other hand, p53 transcriptional inhibitor, PFT-α or p53 siRNA not only inhibited the activation of p53 transcriptional targets but also blocked the activation of c-Jun suggesting the presence of a positive feedback loop between p53 and JNK. In addition, RITA in combination with dexamethasone, known as a JNK activator, displays synergistic cytotoxic responses in MM cell lines and patient samples. Our study unveils a previously undescribed mechanism of RITA-induced p53-mediated apoptosis through JNK signaling pathway and provides the rationale for combination of p53 activating drugs with JNK

Targeting p53 via JNK pathway: a novel role of RITA for apoptotic signaling in multiple myeloma.

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Manujendra N Saha

Full Text Available The low frequency of p53 alterations e.g., mutations/deletions (∼10% in multiple myeloma (MM makes this tumor type an ideal candidate for p53-targeted therapies. RITA is a small molecule which can induce apoptosis in tumor cells by activating the p53 pathway. We previously showed that RITA strongly activates p53 while selectively inhibiting growth of MM cells without inducing genotoxicity, indicating its potential as a drug lead for p53-targeted therapy in MM. However, the molecular mechanisms underlying the pro-apoptotic effect of RITA are largely undefined. Gene expression analysis by microarray identified a significant number of differentially expressed genes associated with stress response including c-Jun N-terminal kinase (JNK signaling pathway. By Western blot analysis we further confirmed that RITA induced activation of p53 in conjunction with up-regulation of phosphorylated ASK-1, MKK-4 and c-Jun. These results suggest that RITA induced the activation of JNK signaling. Chromatin immunoprecipitation (ChIP analysis showed that activated c-Jun binds to the activator protein-1 (AP-1 binding site of the p53 promoter region. Disruption of the JNK signal pathway by small interfering RNA (siRNA against JNK or JNK specific inhibitor, SP-600125 inhibited the activation of p53 and attenuated apoptosis induced by RITA in myeloma cells carrying wild type p53. On the other hand, p53 transcriptional inhibitor, PFT-α or p53 siRNA not only inhibited the activation of p53 transcriptional targets but also blocked the activation of c-Jun suggesting the presence of a positive feedback loop between p53 and JNK. In addition, RITA in combination with dexamethasone, known as a JNK activator, displays synergistic cytotoxic responses in MM cell lines and patient samples. Our study unveils a previously undescribed mechanism of RITA-induced p53-mediated apoptosis through JNK signaling pathway and provides the rationale for combination of p53 activating drugs with

Targeting loss of the Hippo signaling pathway in NF2-deficient papillary kidney cancers

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Ricketts, Christopher J.; Wei, Darmood; Yang, Youfeng; Baranes, Sarah M.; Gibbs, Benjamin K.; Ohanjanian, Lernik; Spencer Krane, L.; Scroggins, Bradley T.; Keith Killian, J.; Wei, Ming-Hui; Kijima, Toshiki; Meltzer, Paul S.; Citrin, Deborah E.; Neckers, Len; Vocke, Cathy D.; Marston Linehan, W.

2018-01-01

Papillary renal cell carcinomas (PRCC) are a histologically and genetically heterogeneous group of tumors that represent 15–20% of all kidney neoplasms and may require diverse therapeutic approaches. Alteration of the NF2 tumor suppressor gene, encoding a key regulator of the Hippo signaling pathway, is observed in 22.5% of PRCC. The Hippo signaling pathway controls cell proliferation by regulating the transcriptional activity of Yes-Associated Protein, YAP1. Loss of NF2 results in aberrant YAP1 activation. The Src family kinase member Yes also regulates YAP1 transcriptional activity. This study investigated the importance of YAP and Yes activity in three NF2-deficient PRCC cell lines. NF2-deficency correlated with increased expression of YAP1 transcriptional targets and siRNA-based knockdown of YAP1 and Yes1 downregulated this pathway and dramatically reduced cell viability. Dasatinib and saracatinib have potent inhibitory effects on Yes and treatment with either resulted in downregulation of YAP1 transcription targets, reduced cell viability, and G0-G1 cell cycle arrest. Xenograft models for NF2-deficient PRCC also demonstrated reduced tumor growth in response to dasatinib. Thus, inhibiting Yes and the subsequent transcriptional activity of YAP1 had a substantial anti-tumor cell effect both in vitro and in vivo and may provide a viable therapeutic approach for patients with NF2-deficient PRCC. PMID:29535838

KSHV Entry and Trafficking in Target Cells—Hijacking of Cell Signal Pathways, Actin and Membrane Dynamics

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Binod Kumar

2016-11-01

Full Text Available Kaposi’s sarcoma associated herpesvirus (KSHV is etiologically associated with human endothelial cell hyperplastic Kaposi’s sarcoma and B-cell primary effusion lymphoma. KSHV infection of adherent endothelial and fibroblast cells are used as in vitro models for infection and KSHV enters these cells by host membrane bleb and actin mediated macropinocytosis or clathrin endocytosis pathways, respectively. Infection in endothelial and fibroblast cells is initiated by the interactions between multiple viral envelope glycoproteins and cell surface associated heparan sulfate (HS, integrins (α3β1, αVβ3 and αVβ5, and EphA2 receptor tyrosine kinase (EphA2R. This review summarizes the accumulated studies demonstrating that KSHV manipulates the host signal pathways to enter and traffic in the cytoplasm of the target cells, to deliver the viral genome into the nucleus, and initiate viral gene expression. KSHV interactions with the cell surface receptors is the key platform for the manipulations of host signal pathways which results in the simultaneous induction of FAK, Src, PI3-K, Rho-GTPase, ROS, Dia-2, PKC ζ, c-Cbl, CIB1, Crk, p130Cas and GEF-C3G signal and adaptor molecules that play critical roles in the modulation of membrane and actin dynamics, and in the various steps of the early stages of infection such as entry and trafficking towards the nucleus. The Endosomal Sorting Complexes Required for Transport (ESCRT proteins are also recruited to assist in viral entry and trafficking. In addition, KSHV interactions with the cell surface receptors also induces the host transcription factors NF-κB, ERK1/2, and Nrf2 early during infection to initiate and modulate viral and host gene expression. Nuclear delivery of the viral dsDNA genome is immediately followed by the host innate responses such as the DNA damage response (DDR, inflammasome and interferon responses. Overall, these studies form the initial framework for further studies of

Identifying novel targets of oncogenic EGF receptor signaling in lung cancer through global phosphoproteomics.

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Zhang, Xu; Belkina, Natalya; Jacob, Harrys Kishore Charles; Maity, Tapan; Biswas, Romi; Venugopalan, Abhilash; Shaw, Patrick G; Kim, Min-Sik; Chaerkady, Raghothama; Pandey, Akhilesh; Guha, Udayan

2015-01-01

Mutations in the epidermal growth factor receptor (EGFR) kinase domain occur in 10-30% of lung adenocarcinoma and are associated with tyrosine kinase inhibitor (TKI) sensitivity. We sought to identify the immediate direct and indirect phosphorylation targets of mutant EGFRs in lung adenocarcinoma. We undertook SILAC strategy, phosphopeptide enrichment, and quantitative MS to identify dynamic changes of phosphorylation downstream of mutant EGFRs in lung adenocarcinoma cells harboring EGFR(L858R) and EGFR(L858R/T790M) , the TKI-sensitive, and TKI-resistant mutations, respectively. Top canonical pathways that were inhibited upon erlotinib treatment in sensitive cells, but not in the resistant cells include EGFR, insulin receptor, hepatocyte growth factor, mitogen-activated protein kinase, mechanistic target of rapamycin, ribosomal protein S6 kinase beta 1, and Janus kinase/signal transducer and activator of transcription signaling. We identified phosphosites in proteins of the autophagy network, such as ULK1 (S623) that is constitutively phosphorylated in these lung adenocarcinoma cells; phosphorylation is inhibited upon erlotinib treatment in sensitive cells, but not in resistant cells. Finally, kinase-substrate prediction analysis from our data indicated that substrates of basophilic kinases from, AGC and Calcium and calmodulin-dependent kinase groups, as well as STE group kinases were significantly enriched and those of proline-directed kinases from, CMGC and Casein kinase groups were significantly depleted among substrates that exhibited increased phosphorylation upon EGF stimulation and reduced phosphorylation upon TKI inhibition. This is the first study to date to examine global phosphorylation changes upon erlotinib treatment of lung adenocarcinoma cells and results from this study provide new insights into signaling downstream of mutant EGFRs in lung adenocarcinoma. All MS data have been deposited in the ProteomeXchange with identifier PXD001101 (http

Sn-doped polyhedral In2O3 particles: Synthesis, characterization, and origins of luminous emission in wide visible range

International Nuclear Information System (INIS)

Zhu Yunqing; Chen Yiqing

2012-01-01

Sn-doped octahedronal and tetrakaidecahedronal In 2 O 3 particles were successfully synthesized by simple thermal evaporation of indium grains using SnO as dopant. Structural characterization results demonstrated that the Sn-doped tetrakaidecahedronal In 2 O 3 particle had additional six {001} crystal surfaces compared with the octahedronal one. The luminous properties of both samples were characterized by photoluminescence (PL) and cathodoluminescence (CL) spectroscopy. A broad visible luminous emission around 570 nm was observed. Studies revealed that the emission consisted of three peaks of 511 nm, 564 nm, and 622 nm, which were attributed to radioactive recombination centers such as single ionized oxygen vacancy, indium interstitial, and antisite oxygen, respectively. We believe that the Sn donor level plays an important role in the visible luminous emission. - Graphical abstract: With more oxygen vacancies and tin doping. ITO particles can exhibit a better CL performance. Sn donor level near the conduction band edge plays an important role in luminous emission in wide visible range. Highlights: ► Polyhedral ITO particles synthesized by thermal evaporation using SnO as dopant. ► Broad visible luminous emission around 570 nm. ► Sn donor level plays an important role in the visible emission. ► ITO particles with more oxygen vacancies have better CL performance in visible range.

Endoscopic visualization of luminal organ and great vessels with three dimensional CT scanner

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Kobayashi, Hisashi; Okumura, Toshiyuki; Amemiya, Ryuta; Hasegawa, Hiroshi

1992-01-01

Thirty cases examined by three dimensional CT scanner (3DCT) are reported. The observation of inner view using 3DCT were performed in 12 large vessels with vascular disorder, 10 pulmonary bronchi with lung cancer and 8 common bile ducts involved obstructive disease. In order to visualize interface of the lumen, a new software, which was developed by HITACHI MEDICO Inc., was used. In all cases but one the inner view of the luminal organ was clearly demonstrated as 3D images and it was possible to judge some changes of luminal interface involved by the diseases. The 3DCT endoscopic image might be useful as a new endoscopic technique without fiberscopy. (author)

Canonical and non-canonical WNT signaling in cancer stem cells and their niches: Cellular heterogeneity, omics reprogramming, targeted therapy and tumor plasticity (Review)

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Katoh, Masaru

2017-01-01

Cancer stem cells (CSCs), which have the potential for self-renewal, differentiation and de-differentiation, undergo epigenetic, epithelial-mesenchymal, immunological and metabolic reprogramming to adapt to the tumor microenvironment and survive host defense or therapeutic insults. Intra-tumor heterogeneity and cancer-cell plasticity give rise to therapeutic resistance and recurrence through clonal replacement and reactivation of dormant CSCs, respectively. WNT signaling cascades cross-talk with the FGF, Notch, Hedgehog and TGFβ/BMP signaling cascades and regulate expression of functional CSC markers, such as CD44, CD133 (PROM1), EPCAM and LGR5 (GPR49). Aberrant canonical and non-canonical WNT signaling in human malignancies, including breast, colorectal, gastric, lung, ovary, pancreatic, prostate and uterine cancers, leukemia and melanoma, are involved in CSC survival, bulk-tumor expansion and invasion/metastasis. WNT signaling-targeted therapeutics, such as anti-FZD1/2/5/7/8 monoclonal antibody (mAb) (vantictumab), anti-LGR5 antibody-drug conjugate (ADC) (mAb-mc-vc-PAB-MMAE), anti-PTK7 ADC (PF-06647020), anti-ROR1 mAb (cirmtuzumab), anti-RSPO3 mAb (rosmantuzumab), small-molecule porcupine inhibitors (ETC-159, WNT-C59 and WNT974), tankyrase inhibitors (AZ1366, G007-LK, NVP-TNKS656 and XAV939) and β-catenin inhibitors (BC2059, CWP232228, ICG-001 and PRI-724), are in clinical trials or preclinical studies for the treatment of patients with WNT-driven cancers. WNT signaling-targeted therapeutics are applicable for combination therapy with BCR-ABL, EGFR, FLT3, KIT or RET inhibitors to treat a subset of tyrosine kinase-driven cancers because WNT and tyrosine kinase signaling cascades converge to β-catenin for the maintenance and expansion of CSCs. WNT signaling-targeted therapeutics might also be applicable for combination therapy with immune checkpoint blockers, such as atezolizumab, avelumab, durvalumab, ipilimumab, nivolumab and pembrolizumab, to treat cancers

Increased luminance of MEH-PPV and PFO based PLEDs by using salmon DNA as an electron blocking layer

International Nuclear Information System (INIS)

Madhwal, Devinder; Rait, S.S.; Verma, A.; Kumar, Amit; Bhatnagar, P.K.; Mathur, P.C.; Onoda, M.

2010-01-01

The effect of salmon DNA-CTMA as an electron blocking layer (EBL) has been examined on the performance of MEH-PPV and PFO-based light emitting diodes. Though the turn-on voltage increases with incorporation of EBL, a significant increase in luminance and luminous efficiency for both the devices is observed. The EBL improves the device performance by blocking electrons at the EBL-polymer interface, thereby increasing the recombination probability of electrons and holes. The luminance of the MEH-PPV based Bio-LED increases to 100 cd/m 2 from 30 cd/m 2 while a corresponding increase for the PFO based LED is to 160 cd/m 2 from 80 cd/m 2 with and without EBL, respectively.

Symbiotic association of Photobacterium fischeri with the marine luminous fish Monocentris japonica; a model of symbiosis based on bacterial studies.

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Ruby, E G; Nealson, K H

1976-12-01

Isolation of bacteria from the luminous organ of the fish Monocentris japonica has revealed that the organ contains a pure culture of luminous bacteria. For the four fish examined, all contained Photobacterium fischeri as their luminous bacterial symbiont. This is the first time that P. fischeri has been identified in a symbiotic association. A representative isolate (MJl) of the light organ population was selected for in vivo studies of its luminous system. Several physiological features suggest adaptation for symbiotic existence. First, MJl has been shown to produce and respond to an inducer of luciferase that could accumulate in the light organ. Secondly, the specific activity of light production was seen to be maximal under low, growth-limiting concentrations of oxygen. Thirdly, unlike another luminous species (Beneckea harveyi), synthesis of the light production system of these bacteria is not catabolite repressed by glucose--a possible source of nutrition in the light organ. Fourthly, when grown aerobically on glucose these bacteria excrete pyruvic acid into the medium. This production of pyruvate is a major process, accounting for 30-40% of the glucose utilized and may serve as a form of regulatory and nutritional communication with the host.

Luminous quasars do not live in the most overdense regions of galaxies at z ˜ 4

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Uchiyama, Hisakazu; Toshikawa, Jun; Kashikawa, Nobunari; Overzier, Roderik; Chiang, Yi-Kuan; Marinello, Murilo; Tanaka, Masayuki; Niino, Yuu; Ishikawa, Shogo; Onoue, Masafusa; Ichikawa, Kohei; Akiyama, Masayuki; Coupon, Jean; Harikane, Yuichi; Imanishi, Masatoshi; Kodama, Tadayuki; Komiyama, Yutaka; Lee, Chien-Hsiu; Lin, Yen-Ting; Miyazaki, Satoshi; Nagao, Tohru; Nishizawa, Atsushi J.; Ono, Yoshiaki; Ouchi, Masami; Wang, Shiang-Yu

2018-01-01

We present the cross-correlation between 151 luminous quasars (MUV 4 σ. The distributions of the distances between quasars and the nearest protoclusters and the significance of the overdensity at the positions of quasars are statistically identical to those found for g-dropout galaxies, suggesting that quasars tend to reside in almost the same environment as star-forming galaxies at this redshift. Using stacking analysis, we find that the average density of g-dropout galaxies around quasars is slightly higher than that around g-dropout galaxies on 1.0-2.5 pMpc scales, while at anti-correlated with overdensity. These findings are consistent with a scenario in which luminous quasars at z ˜ 4 reside in structures that are less massive than those expected for the progenitors of today's rich clusters of galaxies, and possibly that luminous quasars may be suppressing star formation in their close vicinity.

Luminance and image quality analysis of an organic electroluminescent panel with a patterned microlens array attachment

International Nuclear Information System (INIS)

Lin, Hoang Yan; Chen, Kuan-Yu; Ho, Yu-Hsuan; Fang, Jheng-Hao; Hsu, Sheng-Chih; Lee, Jiun-Haw; Lin, Jia-Rong; Wei, Mao-Kuo

2010-01-01

Luminance and image quality observed from the normal direction of a commercial 2.0 inch panel based on organic electroluminescence (OEL) technology attached to regular and patterned microlens array films (MAFs) were studied and analyzed. When applying the regularly arranged MAF on the panel, a luminance enhancement of 23% was observed, accompanied by a reduction of the image quality index as low as 74%. By removing the microlenses on the emitting areas, the patterned MAF enhances the luminance efficiency of the OEL by 52% keeping the image quality index of the display as high as 94%, due to the effective light extraction in the glass substrate being less than the critical angle. 3D simulation based on a ray-tracing model was also established to investigate the spatial distribution of light rays radiated from an OEL pixel with different microstructures which showed consistent results with the experimental results

Signal and data processing of small targets 1990; Proceedings of the Meeting, Orlando, FL, Apr. 16-18, 1990

Science.gov (United States)

Drummond, Oliver E.

Various papers on signal and data processing of small targets are presented. Individual topics addressed include: clutter rejection using multispectral processing, new sensor for automatic guidance, Doppler domain localized generalized-likelihood-ratio detector, linear filter for resolution of point sources, analysis of order-statistic filters for robust detection, distribution functions for additive Gaussian and gamma noise, temperature discrimination of closely space objects, knowledge-based tracking algorithm, detecting and tracking low-observable targets using IR, weak target detection using the entropy concept, measurement-based neural-net multitarget tracker, object-track closed-form solution in angle space, passive-sensor data association for tracking. Also discussed are: application of MHT to dim moving targets, automatic static covariance analysis with mathematica, neural network implementation of plot/track association, application of Bayesian networks to multitarget tracking, tracking clusters and extended objects with multiple sensors, target tracking by human operator, finite impulse response estimator, multitarget tracking using an extended Kalman filter, maneuvering target tracking using a two-state model algorithm, mixture reduction algorithms for target tracking in clutter, scene interpretation approach to high-level target tracking.

Omission of Breast Radiotherapy in Low-risk Luminal A Breast Cancer: Impact on Health Care Costs.

Science.gov (United States)

Han, K; Yap, M L; Yong, J H E; Mittmann, N; Hoch, J S; Fyles, A W; Warde, P; Gutierrez, E; Lymberiou, T; Foxcroft, S; Liu, F F

2016-09-01

The economic burden of cancer care is substantial, including steep increases in costs for breast cancer management. There is mounting evidence that women age ≥ 60 years with grade I/II T1N0 luminal A (ER/PR+, HER2- and Ki67 ≤ 13%) breast cancer have such low local recurrence rates that adjuvant breast radiotherapy might offer limited value. We aimed to determine the total savings to a publicly funded health care system should omission of radiotherapy become standard of care for these patients. The number of women aged ≥ 60 years who received adjuvant radiotherapy for T1N0 ER+ HER2- breast cancer in Ontario was obtained from the provincial cancer agency. The cost of adjuvant breast radiotherapy was estimated through activity-based costing from a public payer perspective. The total saving was calculated by multiplying the estimated number of luminal A cases that received radiotherapy by the cost of radiotherapy minus Ki-67 testing. In 2010, 748 women age ≥ 60 years underwent surgery for pT1N0 ER+ HER2- breast cancer; 539 (72%) underwent adjuvant radiotherapy, of whom 329 were estimated to be grade I/II luminal A subtype. The cost of adjuvant breast radiotherapy per case was estimated at $6135.85; the cost of Ki-67 at $114.71. This translated into an annual saving of about $2.0million if radiotherapy was omitted for all low-risk luminal A breast cancer patients in Ontario and $5.1million across Canada. There will be significant savings to the health care system should omission of radiotherapy become standard practice for women with low-risk luminal A breast cancer. Copyright © 2016 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Quorum sensing communication between bacteria and human cells: signals, targets and functions

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Angelika eHolm

2014-06-01

Full Text Available Both direct and long-range interactions between pathogenic Pseudomonas aeruginosa bacteria and their eukaryotic hosts are important in the outcome of infections. For cell-to-cell communication, these bacteria employ the quorum sensing (QS system to pass on information of the density of the bacterial population and collectively switch on virulence factor production, biofilm formation and resistance development. Thus, QS allows bacteria to behave as a community to perform tasks which would be impossible for individual cells, e.g. to overcome defense and immune systems and establish infections in higher organisms. This review highlights these aspects of QS and our own recent research on how P.aeruginosa communicates with human cells using the small QS signal molecules N-acyl homoserine lactones (AHL. We focus on how this conversation changes the behavior and function of neutrophils, macrophages and epithelial cells and on how the signaling machinery in human cells responsible for the recognition of AHL. Understanding the bacteria-host relationships at both cellular and molecular levels is essential for the identification of new targets and for the development of novel strategies to fight bacterial infections in the future.

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

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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.

Intratumoral estrogen production and actions in luminal A type invasive lobular and ductal carcinomas.

Science.gov (United States)

Takagi, Mayu; Miki, Yasuhiro; Miyashita, Minoru; Hata, Shuko; Yoda, Tomomi; Hirakawa, Hisashi; Sagara, Yasuaki; Rai, Yoshiaki; Ohi, Yasuyo; Tamaki, Kentaro; Ishida, Takanori; Suzuki, Takashi; Ouchi, Noriaki; Sasano, Hironobu

2016-02-01

The great majority of invasive lobular carcinoma (ILC) is estrogen-dependent luminal A type carcinoma but the details of estrogen actions and its intratumoral metabolism have not been well studied compared to invasive ductal carcinoma (IDC). We first immunolocalized estrogen-related enzymes including estrogen sulfotransferase (EST), estrogen sulfatase (STS), 17β-hydroxysteroid dehydrogenase (HSD) 1/2, and aromatase. We then evaluated the tissue concentrations of estrogens in ILC and IDC and subsequently estrogen-responsive gene profiles in these tumors in order to explore the possible differences and/or similarity of intratumoral estrogen environment of these two breast cancer subtypes. The status of STS and 17βHSD1 was significantly lower in ILCs than IDCs (p = 0.022 and p < 0.0001), but that of EST and 17βHSD2 vice versa (p < 0.0001 and p = 0.0106). In ILCs, tissue concentrations of estrone and estradiol were lower than those in IDCs (p = 0.0709 and 0.069). In addition, the great majority of estrogen response genes tended to be lower in ILCs. Among those genes above, FOXP1 was significantly higher in ILCs than in IDCs (p = 0.002). FOXP1 expression was reported to be significantly higher in relapse-free IDC patients treated with tamoxifen. Therefore, tamoxifen may be considered an option of endocrine therapy for luminal A type ILC patients. This is the first study to demonstrate the detailed and comprehensive status of intratumoral production and metabolism of estrogens and the status of estrogen response genes in luminal A-like ILC with comparison to those in luminal A-like IDCs.

P-glycoprotein trafficking as a therapeutic target to optimize CNS drug delivery.

Science.gov (United States)

Davis, Thomas P; Sanchez-Covarubias, Lucy; Tome, Margaret E

2014-01-01

The primary function of the blood-brain barrier (BBB)/neurovascular unit is to protect the central nervous system (CNS) from potentially harmful xenobiotic substances and maintain CNS homeostasis. Restricted access to the CNS is maintained via a combination of tight junction proteins as well as a variety of efflux and influx transporters that limits the transcellular and paracellular movement of solutes. Of the transporters identified at the BBB, P-glycoprotein (P-gp) has emerged as the transporter that is the greatest obstacle to effective CNS drug delivery. In this chapter, we provide data to support intracellular protein trafficking of P-gp within cerebral capillary microvessels as a potential target for improved drug delivery. We show that pain-induced changes in P-gp trafficking are associated with changes in P-gp's association with caveolin-1, a key scaffolding/trafficking protein that colocalizes with P-gp at the luminal membrane of brain microvessels. Changes in colocalization with the phosphorylated and nonphosphorylated forms of caveolin-1, by pain, are accompanied by dynamic changes in the distribution, relocalization, and activation of P-gp "pools" between microvascular endothelial cell subcellular compartments. Since redox-sensitive processes may be involved in signaling disassembly of higher-order structures of P-gp, we feel that manipulating redox signaling, via specific protein targeting at the BBB, may protect disulfide bond integrity of P-gp reservoirs and control trafficking to the membrane surface, providing improved CNS drug delivery. The advantage of therapeutic drug "relocalization" of a protein is that the physiological impact can be modified, temporarily or long term, despite pathology-induced changes in gene transcription. © 2014 Elsevier Inc. All rights reserved.

Effect of low-dose ionizing radiation on luminous marine bacteria: radiation hormesis and toxicity

International Nuclear Information System (INIS)

Kudryasheva, N.S.; Rozhko, T.V.

2015-01-01

The paper summarizes studies of effects of alpha- and beta-emitting radionuclides (americium-241, uranium-235+238, and tritium) on marine microorganisms under conditions of chronic low-dose irradiation in aqueous media. Luminous marine bacteria were chosen as an example of these microorganisms; bioluminescent intensity was used as a tested physiological parameter. Non-linear dose-effect dependence was demonstrated. Three successive stages in the bioluminescent response to americium-241 and tritium were found: 1 – absence of effects (stress recognition), 2 – activation (adaptive response), and 3 – inhibition (suppression of physiological function, i.e. radiation toxicity). The effects were attributed to radiation hormesis phenomenon. Biological role of reactive oxygen species, secondary products of the radioactive decay, is discussed. The study suggests an approach to evaluation of non-toxic and toxic stages under conditions of chronic radioactive exposure. - Highlights: • Luminous bacteria demonstrate nonlinear dose-effect relation in radioactive solutions. • Response to low-dose radiation includes 3 stages: threshold, activation, inhibition. • ROS are responsible for low-dose effects of alpha-emitting radionuclides. • Luminous marine bacteria are a convenient tool to study radiation hormesis

Rapid determination of the toxicity of quantum dots with luminous bacteria

Energy Technology Data Exchange (ETDEWEB)

Wang Lingling [Key Laboratory on Luminescence and Real-Time Analysis, Ministry of Education, College of Chemistry and Chemical Engineering, Southwest University, No. 2 Tiansheng Road, Beibei District, Chongqing 400715 (China); Zheng Huzhi, E-mail: zhenghz@swu.edu.cn [Key Laboratory on Luminescence and Real-Time Analysis, Ministry of Education, College of Chemistry and Chemical Engineering, Southwest University, No. 2 Tiansheng Road, Beibei District, Chongqing 400715 (China); Long Yijuan; Gao Mei; Hao Jianyu; Du Juan; Mao Xiaojiao; Zhou Dongbo [Key Laboratory on Luminescence and Real-Time Analysis, Ministry of Education, College of Chemistry and Chemical Engineering, Southwest University, No. 2 Tiansheng Road, Beibei District, Chongqing 400715 (China)

2010-05-15

In this paper, a novel method so-called bioluminescence inhibition assay with luminous bacteria (Photobacterium phosphoreum) was introduced to evaluate the toxicity of quantum dots. The bioassay was based on measuring the decrease of the light emitted by luminous bacteria. With obvious advantages of simplicity, rapidity and sensitivity, it can dramatically improve the efficiency of probing the toxicity of QDs. Based on this method, we systemically explored the effect of the composition and surface modification on QDs' toxicity. The experiment of composition effect was performed using three kinds of QDs, namely CdSe, CdTe and ZnS-AgInS{sub 2} QDs with the same stabilizer - dihydrolipoic acid. As for the effect of different stabilizers, mercaptoacetic acid, L-cysteine and dihydrolipoic acid stabilized CdSe were researched, respectively. Our results demonstrated that both the composition and surface modification were the important factors affecting the toxicity of QDs. In addition, a concentration dependence of toxicity was also found.

Rapid determination of the toxicity of quantum dots with luminous bacteria

International Nuclear Information System (INIS)

Wang Lingling; Zheng Huzhi; Long Yijuan; Gao Mei; Hao Jianyu; Du Juan; Mao Xiaojiao; Zhou Dongbo

2010-01-01

In this paper, a novel method so-called bioluminescence inhibition assay with luminous bacteria (Photobacterium phosphoreum) was introduced to evaluate the toxicity of quantum dots. The bioassay was based on measuring the decrease of the light emitted by luminous bacteria. With obvious advantages of simplicity, rapidity and sensitivity, it can dramatically improve the efficiency of probing the toxicity of QDs. Based on this method, we systemically explored the effect of the composition and surface modification on QDs' toxicity. The experiment of composition effect was performed using three kinds of QDs, namely CdSe, CdTe and ZnS-AgInS 2 QDs with the same stabilizer - dihydrolipoic acid. As for the effect of different stabilizers, mercaptoacetic acid, L-cysteine and dihydrolipoic acid stabilized CdSe were researched, respectively. Our results demonstrated that both the composition and surface modification were the important factors affecting the toxicity of QDs. In addition, a concentration dependence of toxicity was also found.

Mycobacterium tuberculosis Controls Phagosomal Acidification by Targeting CISH-Mediated Signaling

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Christophe J. Queval

2017-09-01

Full Text Available Pathogens have evolved a range of mechanisms to counteract host defenses, notably to survive harsh acidic conditions in phagosomes. In the case of Mycobacterium tuberculosis, it has been shown that regulation of phagosome acidification could be achieved by interfering with the retention of the V-ATPase complexes at the vacuole. Here, we present evidence that M. tuberculosis resorts to yet another strategy to control phagosomal acidification, interfering with host suppressor of cytokine signaling (SOCS protein functions. More precisely, we show that infection of macrophages with M. tuberculosis leads to granulocyte-macrophage colony-stimulating factor (GM-CSF secretion, inducing STAT5-mediated expression of cytokine-inducible SH2-containing protein (CISH, which selectively targets the V-ATPase catalytic subunit A for ubiquitination and degradation by the proteasome. Consistently, we show that inhibition of CISH expression leads to reduced replication of M. tuberculosis in macrophages. Our findings further broaden the molecular understanding of mechanisms deployed by bacteria to survive.

Targeting AMPK Signaling as a Neuroprotective Strategy in Parkinson's Disease.

Science.gov (United States)

Curry, Daniel W; Stutz, Bernardo; Andrews, Zane B; Elsworth, John D

2018-03-26

Parkinson's disease (PD) is the second most common neurodegenerative disorder. It is characterized by the accumulation of intracellular α-synuclein aggregates and the degeneration of nigrostriatal dopaminergic neurons. While no treatment strategy has been proven to slow or halt the progression of the disease, there is mounting evidence from preclinical PD models that activation of 5'-AMP-activated protein kinase (AMPK) may have broad neuroprotective effects. Numerous dietary supplements and pharmaceuticals (e.g., metformin) that increase AMPK activity are available for use in humans, but clinical studies of their effects in PD patients are limited. AMPK is an evolutionarily conserved serine/threonine kinase that is activated by falling energy levels and functions to restore cellular energy balance. However, in response to certain cellular stressors, AMPK activation may exacerbate neuronal atrophy and cell death. This review describes the regulation and functions of AMPK, evaluates the controversies in the field, and assesses the potential of targeting AMPK signaling as a neuroprotective treatment for PD.

Distribution and species composition of planktonic luminous bacteria in the Arabian Sea

Digital Repository Service at National Institute of Oceanography (India)

Ramaiah, N.; Chandramohan, D.

Distribution of the total viable heterotrophic bacteria and the luminous bacteria in the neretic and oceanic waters of the west coast of India was studied. Counts of viable heterotrophs fluctuated widely, generally with a decrease in their number...

Phosphoproteomic profiling of in vivo signaling in liver by the mammalian target of rapamycin complex 1 (mTORC1.

Directory of Open Access Journals (Sweden)

Gokhan Demirkan

Full Text Available Our understanding of signal transduction networks in the physiological context of an organism remains limited, partly due to the technical challenge of identifying serine/threonine phosphorylated peptides from complex tissue samples. In the present study, we focused on signaling through the mammalian target of rapamycin (mTOR complex 1 (mTORC1, which is at the center of a nutrient- and growth factor-responsive cell signaling network. Though studied extensively, the mechanisms involved in many mTORC1 biological functions remain poorly understood.We developed a phosphoproteomic strategy to purify, enrich and identify phosphopeptides from rat liver homogenates. Using the anticancer drug rapamycin, the only known target of which is mTORC1, we characterized signaling in liver from rats in which the complex was maximally activated by refeeding following 48 hr of starvation. Using protein and peptide fractionation methods, TiO(2 affinity purification of phosphopeptides and mass spectrometry, we reproducibly identified and quantified over four thousand phosphopeptides. Along with 5 known rapamycin-sensitive phosphorylation events, we identified 62 new rapamycin-responsive candidate phosphorylation sites. Among these were PRAS40, gephyrin, and AMP kinase 2. We observed similar proportions of increased and reduced phosphorylation in response to rapamycin. Gene ontology analysis revealed over-representation of mTOR pathway components among rapamycin-sensitive phosphopeptide candidates.In addition to identifying potential new mTORC1-mediated phosphorylation events, and providing information relevant to the biology of this signaling network, our experimental and analytical approaches indicate the feasibility of large-scale phosphoproteomic profiling of tissue samples to study physiological signaling events in vivo.

Observations of Intermediate-mass Black Holes and Ultra-Luminous X-ray sources

Science.gov (United States)

Colbert, E. J. M.

2003-12-01

I will review various observations that suggest that intermediate-mass black holes (IMBHs) with masses ˜102-104 M⊙ exist in our Universe. I will also discuss some of the limitations of these observations. HST Observations of excess dark mass in globular cluster cores suggest IMBHs may be responsible, and some mass estimates from lensing experiments are nearly in the IMBH range. The intriguing Ultra-Luminous X-ray sources (ULXs, or IXOs) are off-nuclear X-ray point sources with X-ray luminosities LX ≳ 1039 erg s-1. ULXs are typically rare (1 in every 5 galaxies), and the nature of their ultra-luminous emission is currently debated. I will discuss the evidence for IMBHs in some ULXs, and briefly outline some phenomenology. Finally, I will discuss future observations that can be made to search for IMBHs.

THE HOST GALAXY OF THE SUPER-LUMINOUS SN 2010gx AND LIMITS ON EXPLOSIVE 56Ni PRODUCTION

International Nuclear Information System (INIS)

Chen, Ting-Wan; Smartt, Stephen J.; Kotak, Rubina; McCrum, Matt; Fraser, Morgan; Bresolin, Fabio; Kudritzki, Rolf-Peter; Pastorello, Andrea; Valenti, Stefano

2013-01-01

Super-luminous supernovae have a tendency to occur in faint host galaxies which are likely to have low mass and low metallicity. While these extremely luminous explosions have been observed from z = 0.1 to 1.55, the closest explosions allow more detailed investigations of their host galaxies. We present a detailed analysis of the host galaxy of SN 2010gx (z = 0.23), one of the best studied super-luminous type Ic supernovae. The host is a dwarf galaxy (M g = –17.42 ± 0.17) with a high specific star formation rate. It has a remarkably low metallicity of 12 + log (O/H) = 7.5 ± 0.1 dex as determined from the detection of the [O III] λ4363 line. This is the first reliable metallicity determination of a super-luminous stripped-envelope supernova host. We collected deep multi-epoch imaging with Gemini + GMOS between 240 and 560 days after explosion to search for any sign of radioactive 56 Ni, which might provide further insights on the explosion mechanism and the progenitor's nature. We reach griz magnitudes of m AB ∼ 26, but do not detect SN 2010gx at these epochs. The limit implies that any 56 Ni production was similar to or below that of SN 1998bw (a luminous type Ic SN that produced around 0.4 M ☉ of 56 Ni). The low volumetric rates of these supernovae (∼10 –4 of the core-collapse population) could be qualitatively matched if the explosion mechanism requires a combination of low-metallicity (below 0.2 Z ☉ ), high progenitor mass (>60 M ☉ ) and high rotation rate (fastest 10% of rotators).

P1-12: Different Double-Pulse Distinguishability Among the Luminance Opponency, the Red-Green Opponency, and the Blue-Yellow Opponency

Directory of Open Access Journals (Sweden)

Lin Shi

2012-10-01

Full Text Available The inter-stimuli-interval (ISI thresholds of double pulses discrimination were measured to investigate the temporal distinguishability of double pulses of the luminance opponency, the red-green opponency, and the blue-yellow opponency. Double pulses were presented randomly in one of four quadrants, defined by a central fixation cross on a CRT display controlled by the real time sequencer (RTS of the VSG system in 42-bit color mode calibrated with less than 3% display error rate of the 1931 CIE luminance and chromatic coordinate. Each pulse was of duration 6.7 msec and included a Gaussian patch with gradation of tristimulus values from the peak to the background in equal-energy-white (the luminance opponency or isoluminance (the red-green and the blue-yellow opponency configuration. Eleven observers were asked to report the number of pulses (one or two observed while ISI was adjusted by a psi method. Psychometric functions were estimated using the cumulative distribution function of the extreme value distribution. The threshold was the ISI value corresponding with the rate of 63.21% correct answer. Significant differences were found among ISI thresholds of the luminance, blue-yellow, and red-green opponency. Results supported that the temporal distinguishability of double pulses of the luminance opponency, the red-green opponency, and the blue-yellow opponency were significantly different. The difference can be explained by the impulse response functions (IRF with various first peak time among the luminance opponency, the red-green opponency, and the blue-yellow opponency.

Seasonal and geographic distribution of luminous bacteria in the eastern mediterranean sea and the gulf of elat.

Science.gov (United States)

Yetinson, T; Shilo, M

1979-06-01

Luminous bacteria in the Mediterranean Sea and the Gulf of Aqaba-Elat have different distribution patterns. In the Mediterranean Sea, Beneckea harveyi is present all year round, with different subtypes alternating in summer and winter; Photobacterium fischeri was only present during the winter. In the Gulf of Elat, P. leiognathi is present throughout the water column in similar densities during the entire year. This constancy in distribution is presumably due to the near-constancy in water temperature. In summer, Photobacterium leiognathi is replaced by B. harveyi in coastal surface waters. In the hypersaline Bardawil lagoon, only B. harveyi types are present. P. fischeri, a major component of the Mediterranean Sea winter communities, is absent from the lagoon. Luminous Beneckea strains show a great diversity in properties, e.g. temperature range for growth, sensitivity to infection by phages, sensitivity to attack by Bdellovibrio strains, and differences in tolerance to high-salinity shock. Therefore, subdivision of the taxonomic cluster of B. harveyi into subtypes is indicated. The composition of the luminous bacteria communities may serve as indicators of different marine water bodies. The symbiotic luminous bacteria of the light organ of the common Gulf of Elat fish, Photoblepharon palbebratus steinitzi, is different from any of the types described.

Illustration Watermarking for Digital Images: An Investigation of Hierarchical Signal Inheritances for Nested Object-based Embedding

Science.gov (United States)

2007-02-23

approach for signal-level watermark inheritance. 15. SUBJECT TERMS EOARD, Steganography , Image Fusion, Data Mining, Image ...189, Geneva, Switzerland, 2006 [V Block-Luminance and Blue Channel LSB Wet Paper Code Image Watermarking, accepte publication in: Proceedings of...SPIE Electronic Imaging , Security, Steganography , and Wa- termarking of Multimedia Contents IX, 2007 Interaction with a project from German Science

Pursuit Latency for Chromatic Targets

Science.gov (United States)

Mulligan, Jeffrey B.; Ellis, Stephen R. (Technical Monitor)

1998-01-01

The temporal dynamics of eye movement response to a change in direction of stimulus motion has been used to compare the processing speeds of different types of stimuli (Mulligan, ARVO '97). In this study, the pursuit response to colored targets was measured to test the hypothesis that the slow response of the chromatic system (as measured using traditional temporal sensitivity measures such as contrast sensitivity) results in increased eye movement latencies. Subjects viewed a small (0.4 deg) Gaussian spot which moved downward at a speed of 6.6 deg/sec. At a variable time during the trajectory, the dot's direction of motion changed by 30 degrees, either to the right or left. Subjects were instructed to pursue the spot. Eye movements were measured using a video ophthalmoscope with an angular resolution of approximately 1 arc min and a temporal sampling rate of 60 Hz. Stimuli were modulated in chrominance for a variety of hue directions, combined with a range of small luminance increments and decrements, to insure that some of the stimuli fell in the subjects' equiluminance planes. The smooth portions of the resulting eye movement traces were fit by convolving the stimulus velocity with an exponential having variable onset latency, time constant and amplitude. Smooth eye movements with few saccades were observed for all stimuli. Pursuit responses to stimuli having a significant luminance component are well-fit by exponentials having latencies and time constants on the order of 100 msec. Increases in pursuit response latency on the order of 100-200 msec are observed in response to certain stimuli, which occur in pairs of complementary hues, corresponding to the intersection of the stimulus section with the subjects' equiluminant plane. Smooth eye movements can be made in response to purely chromatic stimuli, but are slower than responses to stimuli with a luminance component.

A Semi-Automatic, Remote-Controlled Video Observation System for Transient Luminous Events

DEFF Research Database (Denmark)

Allin, Thomas Højgaard; Neubert, Torsten; Laursen, Steen

2003-01-01

In support for global ELF/VLF observations, HF measurements in France, and conjugate photometry/VLF observations in South Africa, we developed and operated a semi-automatic, remotely controlled video system for the observation of middle-atmospheric transient luminous events (TLEs). Installed...

Ignition target and laser-plasma instabilities

International Nuclear Information System (INIS)

Laffite, S.; Loiseau, P.

2010-01-01

For the first time indirect drive ignition targets have been designed with the constraint of limiting laser-plasma instabilities. The amplification of these instabilities is directly proportional to the luminous flux density, it means to the sizes of the focal spots too. This study shows that increasing the sizes of the focal spots does not reduce linear amplification gains in a proportional way because the global optimization of the target implies changes in hydrodynamical conditions that in turn have an impact on the value of the amplification gain. The design of the target is a 2-step approach: the first step aims at assuring a uniform irradiation and compression of the target. The first step requires information concerning the laser focusing spots, the dimensions of the hohlraum, the inert gas contained in it, the materials of the wall. The second step is an optimization approach whose aim is to reduce the risk of laser-plasmas instabilities. This optimization is made through simulations of the amplification gains of stimulated Raman and Brillouin backscattering. This method has allowed us to design an optimized target for a rugby-shaped hohlraum. (A.C.)

An Assessment of Luminance Imbalance with ANVIS at an Army Helicopter Training Airfield

National Research Council Canada - National Science Library

McLean, William

1997-01-01

One of the casual factors listed in a 1996 mid-air collision between two Australian Army helicopters in formation was a speculation of possible luminance imbalance between the right and left channels...

Targeting Signaling Pathways in Epithelial Ovarian Cancer

Directory of Open Access Journals (Sweden)

Johannes Haybaeck

2013-05-01

Full Text Available Ovarian carcinoma (OC is the most lethal gynecological malignancy. Response to platinum-based chemotherapy is poor in some patients and, thus, current research is focusing on new therapy options. The various histological types of OC are characterized by distinctive molecular genetic alterations that are relevant for ovarian tumorigenesis. The understanding of these molecular pathways is essential for the development of novel therapeutic strategies. Purpose: We want to give an overview on the molecular genetic changes of the histopathological types of OC and their role as putative therapeutic targets. In Depth Review of Existing Data: In 2012, the vascular endothelial growth factor (VEGF inhibitor, bevacizumab, was approved for OC treatment. Bevacizumab has shown promising results as single agent and in combination with conventional chemotherapy, but its target is not distinctive when analyzed before treatment. At present, mammalian target of rapamycin (mTOR inhibitors, poly-ADP-ribose polymerase (PARP inhibitors and components of the EGFR pathway are in the focus of clinical research. Interestingly, some phytochemical substances show good synergistic effects when used in combination with chemotherapy. Conclusion: Ongoing studies of targeted agents in conjunction with chemotherapy will show whether there are alternative options to bevacizumab available for OC patients. Novel targets which can be assessed before therapy to predict efficacy are needed. The assessment of therapeutic targets is continuously improved by molecular pathological analyses on tumor tissue. A careful selection of patients for personalized treatment will help to reduce putative side effects and toxicity.

c-MPL provides tumor-targeted T-cell receptor-transgenic T cells with costimulation and cytokine signals.

Science.gov (United States)

Nishimura, Christopher D; Brenner, Daniel A; Mukherjee, Malini; Hirsch, Rachel A; Ott, Leah; Wu, Meng-Fen; Liu, Hao; Dakhova, Olga; Orange, Jordan S; Brenner, Malcolm K; Lin, Charles Y; Arber, Caroline

2017-12-21

Adoptively transferred T-cell receptor (TCR)-engineered T cells depend on host-derived costimulation and cytokine signals for their full and sustained activation. However, in patients with cancer, both signals are frequently impaired. Hence, we developed a novel strategy that combines both essential signals in 1 transgene by expressing the nonlymphoid hematopoietic growth factor receptor c-MPL (myeloproliferative leukemia), the receptor for thrombopoietin (TPO), in T cells. c-MPL signaling activates pathways shared with conventional costimulatory and cytokine receptor signaling. Thus, we hypothesized that host-derived TPO, present in the tumor microenvironment, or pharmacological c-MPL agonists approved by the US Food and Drug Administration could deliver both signals to c-MPL-engineered TCR-transgenic T cells. We found that c-MPL + polyclonal T cells expand and proliferate in response to TPO, and persist longer after adoptive transfer in immunodeficient human TPO-transgenic mice. In TCR-transgenic T cells, c-MPL activation enhances antitumor function, T-cell expansion, and cytokine production and preserves a central memory phenotype. c-MPL signaling also enables sequential tumor cell killing, enhances the formation of effective immune synapses, and improves antileukemic activity in vivo in a leukemia xenograft model. We identify the type 1 interferon pathway as a molecular mechanism by which c-MPL mediates immune stimulation in T cells. In conclusion, we present a novel immunotherapeutic strategy using c-MPL-enhanced transgenic T cells responding to either endogenously produced TPO (a microenvironment factor in hematologic malignancies) or c-MPL-targeted pharmacological agents. © 2017 by The American Society of Hematology.

MicroRNA expression, target genes, and signaling pathways in infants with a ventricular septal defect.

Science.gov (United States)

Chai, Hui; Yan, Zhaoyuan; Huang, Ke; Jiang, Yuanqing; Zhang, Lin

2018-02-01

This study aimed to systematically investigate the relationship between miRNA expression and the occurrence of ventricular septal defect (VSD), and characterize the miRNA target genes and pathways that can lead to VSD. The miRNAs that were differentially expressed in blood samples from VSD and normal infants were screened and validated by implementing miRNA microarrays and qRT-PCR. The target genes regulated by differentially expressed miRNAs were predicted using three target gene databases. The functions and signaling pathways of the target genes were enriched using the GO database and KEGG database, respectively. The transcription and protein expression of specific target genes in critical pathways were compared in the VSD and normal control groups using qRT-PCR and western blotting, respectively. Compared with the normal control group, the VSD group had 22 differentially expressed miRNAs; 19 were downregulated and three were upregulated. The 10,677 predicted target genes participated in many biological functions related to cardiac development and morphogenesis. Four target genes (mGLUR, Gq, PLC, and PKC) were involved in the PKC pathway and four (ECM, FAK, PI3 K, and PDK1) were involved in the PI3 K-Akt pathway. The transcription and protein expression of these eight target genes were significantly upregulated in the VSD group. The 22 miRNAs that were dysregulated in the VSD group were mainly downregulated, which may result in the dysregulation of several key genes and biological functions related to cardiac development. These effects could also be exerted via the upregulation of eight specific target genes, the subsequent over-activation of the PKC and PI3 K-Akt pathways, and the eventual abnormal cardiac development and VSD.

The uncultured luminous symbiont of Anomalops katoptron (Beryciformes: Anomalopidae) represents a new bacterial genus.

Science.gov (United States)

Hendry, Tory A; Dunlap, Paul V

2011-12-01

Flashlight fishes (Beryciformes: Anomalopidae) harbor luminous symbiotic bacteria in subocular light organs and use the bacterial light for predator avoidance, feeding, and communication. Despite many attempts anomalopid symbionts have not been brought into laboratory culture, which has restricted progress in understanding their phylogenetic relationships with other luminous bacteria, identification of the genes of their luminescence system, as well as the nature of their symbiotic interactions with their fish hosts. To begin addressing these issues, we used culture-independent analysis of the bacteria symbiotic with the anomalopid fish, Anomalops katoptron, to characterize the phylogeny of the bacteria and to identify the genes of their luminescence system including those involved in the regulation of luminescence. Analysis of the 16S rRNA, atpA, gapA, gyrB, pyrH, recA, rpoA, and topA genes resolved the A. katoptron symbionts as a clade nested within and deeply divergent from other members of Vibrionaceae. The bacterial luminescence (lux) genes were identified as a contiguous set (luxCDABEG), as found for the lux operons of other luminous bacteria. Phylogenetic analysis based on the lux genes confirmed the housekeeping gene phylogenetic placement. Furthermore, genes flanking the lux operon in the A. katoptron symbionts differed from those flanking lux operons of other genera of luminous bacteria. We therefore propose the candidate name Candidatus Photodesmus (Greek: photo = light, desmus = servant) katoptron for the species of bacteria symbiotic with A. katoptron. Results of a preliminary genomic analysis for genes regulating luminescence in other bacteria identified only a Vibrio harveyi-type luxR gene. These results suggest that expression of the luminescence system might be continuous in P. katoptron. Copyright © 2011 Elsevier Inc. All rights reserved.

Visual memory for random block patterns defined by luminance and color contrast

NARCIS (Netherlands)

Cornelissen, FW; Greenlee, MW

2000-01-01

We studied the ability of human subjects to memorize the visual information in computer-generated random block patterns defined either by luminance contrast, by color contrast, or by both. Memory performance declines rapidly with increasing inter-stimulus interval, showing a half-life of

High-protein diet modifies colonic microbiota and luminal environment but not colonocyte metabolism in the rat model: the increased luminal bulk connection

OpenAIRE

LIU, Xinxin; BLOUIN, Jean-Marc; Santacruz, Arlette; Lan, Annaig; Andriamihaja, Mireille; Wilkanowicz, Sabina; Benetti, Pierre-Henri; Tomé, Daniel; Sanz, Yolanda; Blachier, Francois; Davila-Gay, Anne-Marie

2014-01-01

High-protein diets are used for body weight reduction, but consequences on the large intestine ecosystem are poorly known. Here, rats were fed for 15 days with either a normoproteic diet (NP, 14% protein) or a hyperproteic-hypoglucidic isocaloric diet (HP, 53% protein). Cecum and colon were recovered for analysis. Short- and branched-chain fatty acids, as well as lactate, succinate, formate, and ethanol contents, were markedly increased in the colonic luminal contents of HP rats (P < 0.05 or ...

Binding and Fusion of Extracellular Vesicles to the Plasma Membrane of Their Cell Targets.

Science.gov (United States)

Prada, Ilaria; Meldolesi, Jacopo

2016-08-09

Exosomes and ectosomes, extracellular vesicles of two types generated by all cells at multivesicular bodies and the plasma membrane, respectively, play critical roles in physiology and pathology. A key mechanism of their function, analogous for both types of vesicles, is the fusion of their membrane to the plasma membrane of specific target cells, followed by discharge to the cytoplasm of their luminal cargo containing proteins, RNAs, and DNA. Here we summarize the present knowledge about the interactions, binding and fusions of vesicles with the cell plasma membrane. The sequence initiates with dynamic interactions, during which vesicles roll over the plasma membrane, followed by the binding of specific membrane proteins to their cell receptors. Membrane binding is then converted rapidly into fusion by mechanisms analogous to those of retroviruses. Specifically, proteins of the extracellular vesicle membranes are structurally rearranged, and their hydrophobic sequences insert into the target cell plasma membrane which undergoes lipid reorganization, protein restructuring and membrane dimpling. Single fusions are not the only process of vesicle/cell interactions. Upon intracellular reassembly of their luminal cargoes, vesicles can be regenerated, released and fused horizontally to other target cells. Fusions of extracellular vesicles are relevant also for specific therapy processes, now intensely investigated.

MicroRNA-1297 inhibits prostate cancer cell proliferation and invasion by targeting the AEG-1/Wnt signaling pathway

International Nuclear Information System (INIS)

Liang, Xuan; Li, Hecheng; Fu, Delai; Chong, Tie; Wang, Ziming; Li, Zhaolun

2016-01-01

MicroRNAs (miRNAs) have been known to be implicated in tumorigenic programs. miR-1297 has been reported to be dysregulated and involved in cancer progression in many types of human cancers. However, the expression level and the role of miR-1297 in prostate cancer remain unclear. Herein, we aimed to investigate the potential role and molecular mechanism of miR-1297 in prostate cancer progression. We found that miR-1297 was significantly downregulated in human prostate cancer specimens as well as in several prostate cancer cell lines. In addition, functional experiments demonstrated that overexpression of miR-1297 remarkably inhibited prostate cancer cell proliferation and invasion whereas miR-1297 suppression significantly promoted prostate cancer cell proliferation and invasion. Bioinformatics analysis showed that the Astrocyte elevated gene-1 (AEG-1), a well-known oncogene, is a predicted target of miR-1297. Dual-luciferase reporter assay showed that miR-1297 was able to directly target the 3’-untranslated region of AEG-1. In addition, RT-qPCR and Western blot analysis showed that miR-1297 regulated the mRNA and protein expression levels of AEG-1. We also showed that miR-1297 was able to regulate the Wnt signaling pathway. Moreover, rescue assays indicated that AEG-1 contributed to miR-1297-endowed effects on cell proliferation and invasion as well as Wnt signaling pathway. Taken together, these findings suggest that miR-1297 inhibits prostate cancer proliferation and invasion by targeting AEG-1, thereby providing novel insight into understanding the pathogenesis of prostate cancer. Thus, miR-1297 may be a novel potential therapeutic candidate to treat prostate cancer. - Highlights: • miR-1297 is decreased in prostate cancer. • miR-1297 inhibits prostate cancer cell proliferation and invasion. • miR-1297 targets and inhibits AEG-1. • miR-1297 regulates AEG-1/Wnt signaling pathway.

Hybrid metal grid-polymer-carbon nanotube electrodes for high luminance organic light emitting diodes

International Nuclear Information System (INIS)

Sam, F Laurent M; Dabera, G Dinesha M R; Lai, Khue T; Mills, Christopher A; Rozanski, Lynn J; Silva, S Ravi P

2014-01-01

Organic light emitting diodes (OLEDs) incorporating grid transparent conducting electrodes (TCEs) with wide grid line spacing suffer from an inability to transfer charge carriers across the gaps in the grids to promote light emission in these areas. High luminance OLEDs fabricated using a hybrid TCE composed of poly(3,4-ethylenedioxythiophene) poly(styrenesulfonate) (PEDOT:PSS PH1000) or regioregular poly(3-hexylthiophene)-wrapped semiconducting single-walled carbon nanotubes (rrP3HT-SWCNT) in combination with a nanometre thin gold grid are reported here. OLEDs fabricated using the hybrid gold grid/PH1000 TCE have a luminance of 18 000 cd m −2 at 9 V; the same as the reference indium tin oxide (ITO) OLED. The gold grid/rrP3HT-SWCNT OLEDs have a lower luminance of 8260 cd m −2 at 9 V, which is likely due to a rougher rrP3HT-SWCNT surface. These results demonstrate that the hybrid gold grid/PH1000 TCE is a promising replacement for ITO in future plastic electronics applications including OLEDs and organic photovoltaics. For applications where surface roughness is not critical, e.g. electrochromic devices or discharge of static electricity, the gold grid/rrP3HT-SWCNT hybrid TCE can be employed. (paper)

Interleukin-10 neutralizing antibody for detection of intestinal luminal levels and as a dietary additive in Eimeria challenged broiler chicks.

Science.gov (United States)

Arendt, Maria K; Sand, Jordan M; Marcone, Taylor M; Cook, Mark E

2016-02-01

Interleukin-10 (IL-10) mRNA levels are increased within intestinal mucosa after Eimeria infection. IL-10 apical receptor presence on enterocytes suggests IL-10 is secreted into the intestinal lumen. Increased IL-10 has been shown to be central to the pathogenesis of numerous intracellular pathogens; we hypothesize luminal secretion of IL-10 enables Eimeria spp. infection in chickens. This study examines intestine luminal IL-10 levels and performance in broilers challenged with Eimeria when fed an anti-IL-10 antibody. Chicks were fed a diet (1 to 21 d) with control or anti-IL-10 antibody (0.34 g egg yolk antibody powder/Kg diet) with a saline or 10× dose of Advent coccidiosis vaccine on d 3. One chick per pen was euthanized on days 2, 4, 7, 10, 13, 16, and 19 post-challenge, bled, and intestines were collected for luminal fluid IL-10 concentrations. Body weight and feed intake were measured on d 21, and oocyst shedding was assessed on d 7 post-challenge. A significant Eimeria × antibody interaction on d 21 body weight (P < 0.05) showed chicks fed control antibody, but not anti-IL-10, had significant reductions in body weight when challenged with Eimeria spp. Oocyst shedding was increased with Eimeria challenge, but dietary antibody had no effect. Plasma carotenoid levels were reduced in Eimeria challenged chicks 4, 7, 10, and 16 days post-challenge compared to unchallenged chicks. Lack of an Eimeria × antibody interaction showed anti-IL-10 was not protective against Eimeria-induced decreases in plasma carotenoids. Eimeria challenge increased intestine luminal IL-10 on days 4 and 7 post-challenge in the cecum and jejunum, respectively, compared to unchallenged. Dietary anti-IL-10 decreased luminal IL-10 in the ileum on day 2 post-challenge when compared to control antibody fed chicks. No interaction between Eimeria challenge and antibody was observed on intestine luminal contents of IL-10, suggesting anti-IL-10 was ineffective at preventing increased Eimeria

Tetherin Suppresses Type I Interferon Signaling by Targeting MAVS for NDP52-Mediated Selective Autophagic Degradation in Human Cells.

Science.gov (United States)

Jin, Shouheng; Tian, Shuo; Luo, Man; Xie, Weihong; Liu, Tao; Duan, Tianhao; Wu, Yaoxing; Cui, Jun

2017-10-19

Tetherin (BST2/CD317) is an interferon-inducible antiviral factor known for its ability to block the release of enveloped viruses from infected cells. Yet its role in type I interferon (IFN) signaling remains poorly defined. Here, we demonstrate that Tetherin is a negative regulator of RIG-I like receptor (RLR)-mediated type I IFN signaling by targeting MAVS. The induction of Tetherin by type I IFN accelerates MAVS degradation via ubiquitin-dependent selective autophagy in human cells. Moreover, Tetherin recruits E3 ubiquitin ligase MARCH8 to catalyze K27-linked ubiquitin chains on MAVS at lysine 7, which serves as a recognition signal for NDP52-dependent autophagic degradation. Taken together, our findings reveal a negative feedback loop of RLR signaling generated by Tetherin-MARCH8-MAVS-NDP52 axis and provide insights into a better understanding of the crosstalk between selective autophagy and optimal deactivation of type I IFN signaling. Copyright © 2017 Elsevier Inc. All rights reserved.

Systematic Identification and Assessment of Therapeutic Targets for Breast Cancer Based on Genome-Wide RNA Interference Transcriptomes

Directory of Open Access Journals (Sweden)

Yang Liu

2017-02-01

Full Text Available With accumulating public omics data, great efforts have been made to characterize the genetic heterogeneity of breast cancer. However, identifying novel targets and selecting the best from the sizeable lists of candidate targets is still a key challenge for targeted therapy, largely owing to the lack of economical, efficient and systematic discovery and assessment to prioritize potential therapeutic targets. Here, we describe an approach that combines the computational evaluation and objective, multifaceted assessment to systematically identify and prioritize targets for biological validation and therapeutic exploration. We first establish the reference gene expression profiles from breast cancer cell line MCF7 upon genome-wide RNA interference (RNAi of a total of 3689 genes, and the breast cancer query signatures using RNA-seq data generated from tissue samples of clinical breast cancer patients in the Cancer Genome Atlas (TCGA. Based on gene set enrichment analysis, we identified a set of 510 genes that when knocked down could significantly reverse the transcriptome of breast cancer state. We then perform multifaceted assessment to analyze the gene set to prioritize potential targets for gene therapy. We also propose drug repurposing opportunities and identify potentially druggable proteins that have been poorly explored with regard to the discovery of small-molecule modulators. Finally, we obtained a small list of candidate therapeutic targets for four major breast cancer subtypes, i.e., luminal A, luminal B, HER2+ and triple negative breast cancer. This RNAi transcriptome-based approach can be a helpful paradigm for relevant researches to identify and prioritize candidate targets for experimental validation.

Expression of squid iridescence depends on environmental luminance and peripheral ganglion control.

Science.gov (United States)

Gonzalez-Bellido, P T; Wardill, T J; Buresch, K C; Ulmer, K M; Hanlon, R T

2014-03-15

Squid display impressive changes in body coloration that are afforded by two types of dynamic skin elements: structural iridophores (which produce iridescence) and pigmented chromatophores. Both color elements are neurally controlled, but nothing is known about the iridescence circuit, or the environmental cues, that elicit iridescence expression. To tackle this knowledge gap, we performed denervation, electrical stimulation and behavioral experiments using the long-fin squid, Doryteuthis pealeii. We show that while the pigmentary and iridescence circuits originate in the brain, they are wired differently in the periphery: (1) the iridescence signals are routed through a peripheral center called the stellate ganglion and (2) the iridescence motor neurons likely originate within this ganglion (as revealed by nerve fluorescence dye fills). Cutting the inputs to the stellate ganglion that descend from the brain shifts highly reflective iridophores into a transparent state. Taken together, these findings suggest that although brain commands are necessary for expression of iridescence, integration with peripheral information in the stellate ganglion could modulate the final output. We also demonstrate that squid change their iridescence brightness in response to environmental luminance; such changes are robust but slow (minutes to hours). The squid's ability to alter its iridescence levels may improve camouflage under different lighting intensities.

Luminous and Variable Stars in M31 and M33. V. The Upper HR Diagram

Energy Technology Data Exchange (ETDEWEB)

Humphreys, Roberta M.; Davidson, Kris; Hahn, David [Minnesota Institute for Astrophysics, 116 Church St SE, University of Minnesota, Minneapolis, MN 55455 (United States); Martin, John C. [Barber Observatory, University of Illinois, Springfield, IL 62703 (United States); Weis, Kerstin, E-mail: roberta@umn.edu [Astronomical Institute, Ruhr-Universitaet Bochum (Germany)

2017-07-20

We present HR diagrams for the massive star populations in M31 and M33, including several different types of emission-line stars: the confirmed luminous blue variables (LBVs), candidate LBVs, B[e] supergiants, and the warm hypergiants. We estimate their apparent temperatures and luminosities for comparison with their respective massive star populations and evaluate the possible relationships of these different classes of evolved, massive stars, and their evolutionary state. Several of the LBV candidates lie near the LBV/S Dor instability strip that supports their classification. Most of the B[e] supergiants, however, are less luminous than the LBVs. Many are very dusty with the infrared flux contributing one-third or more to their total flux. They are also relatively isolated from other luminous OB stars. Overall, their spatial distribution suggests a more evolved state. Some may be post-RSGs (red supergiants) like the warm hypergiants, and there may be more than one path to becoming a B[e] star. There are sufficient differences in the spectra, luminosities, spatial distribution, and the presence or lack of dust between the LBVs and B[e] supergiants to conclude that one group does not evolve into the other.

p-STAT3 in luminal breast cancer: Integrated RNA-protein pooled analysis and results from the BIG 2-98 phase III trial.

Science.gov (United States)

Sonnenblick, Amir; Salgado, Roberto; Brohée, Sylvain; Zahavi, Tamar; Peretz, Tamar; Van den Eynden, Gert; Rouas, Ghizlane; Salmon, Asher; Francis, Prudence A; Di Leo, Angelo; Crown, John P A; Viale, Giuseppe; Daly, Laura; Javdan, Bahar; Fujisawa, Sho; De Azambuja, Evandro; Lieveke, Ameye; Piccart, Martine J; Bromberg, Jacqueline F; Sotiriou, Christos

2018-02-01

In the present study, in order to investigate the role of signal transducer and activator of transcription 3 (STAT3) in estrogen receptor (ER)-positive breast cancer prognosis, we evaluated the phosphorylated STAT3 (p-STAT3) status and investigated its effect on the outcome in a pooled analysis and in a large prospective adjuvant trial. By using the TCGA repository, we developed gene signatures that reflected the level of p-STAT3. Using pooled analysis of the expression data from luminal breast cancer patients, we assessed the effects of the p-STAT3 expression signature on prognosis. We further validated the p-STAT3 prognostic effect using immunohistochemistry (IHC) and immunofluorescence staining of p-STAT3 tissue microarrays from a large randomised prospective trial. Our analysis demonstrated that p-STAT3 expression was elevated in luminal A-type breast cancer (Kruskal-Wallis test, PBIG 2-98 randomised trial. With a median follow-up of 10.1 years, p-STAT3 was associated with a reduced risk of recurrence in ER-positive/HER2-negative breast cancer (Cox univariate HR, 0.66; 95% CI, 0.44-0.98; P=0.04). On the whole, our data indicate that p-STAT3 is associated with an improved outcome in ER-positive breast cancer.

Synergism between Hedgehog-GLI and EGFR signaling in Hedgehog-responsive human medulloblastoma cells induces downregulation of canonical Hedgehog-target genes and stabilized expression of GLI1.

Directory of Open Access Journals (Sweden)

Frank Götschel

Full Text Available Aberrant activation of Hedgehog (HH signaling has been identified as a key etiologic factor in many human malignancies. Signal strength, target gene specificity, and oncogenic activity of HH signaling depend profoundly on interactions with other pathways, such as epidermal growth factor receptor-mediated signaling, which has been shown to cooperate with HH/GLI in basal cell carcinoma and pancreatic cancer. Our experimental data demonstrated that the Daoy human medulloblastoma cell line possesses a fully inducible endogenous HH pathway. Treatment of Daoy cells with Sonic HH or Smoothened agonist induced expression of GLI1 protein and simultaneously prevented the processing of GLI3 to its repressor form. To study interactions between HH- and EGF-induced signaling in greater detail, time-resolved measurements were carried out and analyzed at the transcriptomic and proteomic levels. The Daoy cells responded to the HH/EGF co-treatment by downregulating GLI1, PTCH, and HHIP at the transcript level; this was also observed when Amphiregulin (AREG was used instead of EGF. We identified a novel crosstalk mechanism whereby EGFR signaling silences proteins acting as negative regulators of HH signaling, as AKT- and ERK-signaling independent process. EGFR/HH signaling maintained high GLI1 protein levels which contrasted the GLI1 downregulation on the transcript level. Conversely, a high-level synergism was also observed, due to a strong and significant upregulation of numerous canonical EGF-targets with putative tumor-promoting properties such as MMP7, VEGFA, and IL-8. In conclusion, synergistic effects between EGFR and HH signaling can selectively induce a switch from a canonical HH/GLI profile to a modulated specific target gene profile. This suggests that there are more wide-spread, yet context-dependent interactions, between HH/GLI and growth factor receptor signaling in human malignancies.

THE MOST LUMINOUS GALAXIES DISCOVERED BY WISE

Energy Technology Data Exchange (ETDEWEB)

Tsai, Chao-Wei; Eisenhardt, Peter R. M.; Stern, Daniel; Moustakas, Leonidas A. [Jet Propulsion Laboratory, California Institute of Technology, 4800 Oak Grove Dr., Pasadena, CA 91109 (United States); Wu, Jingwen; Wright, Edward L. [Department of Physics and Astronomy, UCLA, Los Angeles, CA 90095-1547 (United States); Assef, Roberto J. [Núcleo de Astronomía de la Facultad deIngeniería, Universidad Diego Portales, Av. Ejército Libertador 441, Santiago (Chile); Blain, Andrew W. [Department of Physics and Astronomy, University of Leicester, 1 University Road, Leicester, LE1 7RH (United Kingdom); Bridge, Carrie R.; Sayers, Jack [Division of Physics, Math, and Astronomy, California Institute of Technology, Pasadena, CA 91125 (United States); Benford, Dominic J.; Leisawitz, David T. [NASA Goddard Space Flight Center, Greenbelt, MD 20771 (United States); Cutri, Roc M.; Masci, Frank J.; Yan, Lin [Infrared Processing and Analysis Center, California Institute of Technology, Pasadena, CA 91125 (United States); Griffith, Roger L. [Department of Astronomy and Astrophysics, The Pennsylvania State University, 525 Davey Lab, University Park, PA 16802 (United States); Jarrett, Thomas H. [Astronomy Department, University of Cape Town, Private Bag X3, Rondebosch 7701 (South Africa); Lonsdale, Carol J. [National Radio Astronomy Observatory, 520 Edgemont Road, Charlottesville, VA 22903 (United States); Petty, Sara M. [Department of Physics, Virginia Tech, Blacksburg, VA 24061 (United States); Stanford, S. Adam, E-mail: Chao-Wei.Tsai@jpl.nasa.gov [Department of Physics, University of California Davis, One Shields Avenue, Davis, CA 95616 (United States); and others

2015-06-01

We present 20 Wide-field Infrared Survey Explorer (WISE)-selected galaxies with bolometric luminosities L{sub bol} > 10{sup 14} L{sub ☉}, including five with infrared luminosities L{sub IR} ≡ L{sub (rest} {sub 8–1000} {sub μm)} > 10{sup 14} L{sub ☉}. These “extremely luminous infrared galaxies,” or ELIRGs, were discovered using the “W1W2-dropout” selection criteria which requires marginal or non-detections at 3.4 and 4.6 μm (W1 and W2, respectively) but strong detections at 12 and 22 μm in the WISE survey. Their spectral energy distributions are dominated by emission at rest-frame 4–10 μm, suggesting that hot dust with T{sub d} ∼ 450 K is responsible for the high luminosities. These galaxies are likely powered by highly obscured active galactic nuclei (AGNs), and there is no evidence suggesting these systems are beamed or lensed. We compare this WISE-selected sample with 116 optically selected quasars that reach the same L{sub bol} level, corresponding to the most luminous unobscured quasars in the literature. We find that the rest-frame 5.8 and 7.8 μm luminosities of the WISE-selected ELIRGs can be 30%–80% higher than that of the unobscured quasars. The existence of AGNs with L{sub bol} > 10{sup 14} L{sub ☉} at z > 3 suggests that these supermassive black holes are born with large mass, or have very rapid mass assembly. For black hole seed masses ∼10{sup 3} M{sub ☉}, either sustained super-Eddington accretion is needed, or the radiative efficiency must be <15%, implying a black hole with slow spin, possibly due to chaotic accretion.

Mycobacterium tuberculosis Controls Phagosomal Acidification by Targeting CISH-Mediated Signaling.

Science.gov (United States)

Queval, Christophe J; Song, Ok-Ryul; Carralot, Jean-Philippe; Saliou, Jean-Michel; Bongiovanni, Antonino; Deloison, Gaspard; Deboosère, Nathalie; Jouny, Samuel; Iantomasi, Raffaella; Delorme, Vincent; Debrie, Anne-Sophie; Park, Sei-Jin; Gouveia, Joana Costa; Tomavo, Stanislas; Brosch, Roland; Yoshimura, Akihiko; Yeramian, Edouard; Brodin, Priscille

2017-09-26

Pathogens have evolved a range of mechanisms to counteract host defenses, notably to survive harsh acidic conditions in phagosomes. In the case of Mycobacterium tuberculosis, it has been shown that regulation of phagosome acidification could be achieved by interfering with the retention of the V-ATPase complexes at the vacuole. Here, we present evidence that M. tuberculosis resorts to yet another strategy to control phagosomal acidification, interfering with host suppressor of cytokine signaling (SOCS) protein functions. More precisely, we show that infection of macrophages with M. tuberculosis leads to granulocyte-macrophage colony-stimulating factor (GM-CSF) secretion, inducing STAT5-mediated expression of cytokine-inducible SH2-containing protein (CISH), which selectively targets the V-ATPase catalytic subunit A for ubiquitination and degradation by the proteasome. Consistently, we show that inhibition of CISH expression leads to reduced replication of M. tuberculosis in macrophages. Our findings further broaden the molecular understanding of mechanisms deployed by bacteria to survive. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

A new method for calibrating perceptual salience across dimensions in infants: the case of color vs. luminance.

Science.gov (United States)

Kaldy, Zsuzsa; Blaser, Erik A; Leslie, Alan M

2006-09-01

We report a new method for calibrating differences in perceptual salience across feature dimensions, in infants. The problem of inter-dimensional salience arises in many areas of infant studies, but a general method for addressing the problem has not previously been described. Our method is based on a preferential looking paradigm, adapted to determine the relative salience of two stimuli. We report here on the case of stimuli differing in color and luminance, though the method has wider potential. We were able to determine on a psychophysical curve the point at which a color contrast was equally salient to infants as a given luminance contrast. We then used these calibrated, 'iso-salient' stimuli in an object memory study. Results showed that 6.5-month-old infants noticed a color, but not a luminance, change while tracking an occluded object. Our method should have numerous applications in the study of bottom-up effects on infant attention and visual working memory.

Targeting the NFκB signaling pathways for breast cancer prevention and therapy.

Science.gov (United States)

Wang, Wei; Nag, Subhasree A; Zhang, Ruiwen

2015-01-01

The activation of nuclear factor-kappaB (NFκB), a proinflammatory transcription factor, is a commonly observed phenomenon in breast cancer. It facilitates the development of a hormone-independent, invasive, high-grade, and late-stage tumor phenotype. Moreover, the commonly used cancer chemotherapy and radiotherapy approaches activate NFκB, leading to the development of invasive breast cancers that show resistance to chemotherapy, radiotherapy, and endocrine therapy. Inhibition of NFκB results in an increase in the sensitivity of cancer cells to the apoptotic effects of chemotherapeutic agents and radiation and restoring hormone sensitivity, which is correlated with increased disease-free survival in patients with breast cancer. In this review article, we focus on the role of the NFκB signaling pathways in the development and progression of breast cancer and the validity of NFκB as a potential target for breast cancer prevention and therapy. We also discuss the recent findings that NFκB may have tumor suppressing activity in certain cancer types. Finally, this review also covers the state-of-the-art development of NFκB inhibitors for cancer therapy and prevention, the challenges in targeting validation, and pharmacology and toxicology evaluations of these agents from the bench to the bedside.

Bmi-1-targeting suppresses osteosarcoma aggressiveness through the NF-κB signaling pathway

Science.gov (United States)

Liu, Jiaguo; Luo, Bin; Zhao, Meng

2017-01-01

Bone cancer is one of the most lethal malignancies and the specific causes of tumor initiation are not well understood. B-cell-specific Moloney murine leukemia virus integration site 1 protein (Bmi-1) has been reported to be associated with the initiation and progression of osteosarcoma, and as a prognostic indicator in the clinic. In the current study, a full-length antibody targeting Bmi-1 (AbBmi-1) was produced and the preclinical value of Bmi-1-targeted therapy was evaluated in bone carcinoma cells and tumor xenograft mice. The results indicated that the Bmi-1 expression level was markedly upregulated in bone cancer cell lines, and inhibition of Bmi-1 by AbBmi-1 reduced the invasiveness and migration of osteosarcoma cells. Overexpression of Bmi-1 promoted proliferation and angiogenesis, and increased apoptosis resistance induced by cisplatin via the nuclear factor-κB (NF-κB) signal pathway. In addition, AbBmi-1 treatment inhibited the tumorigenicity of osteosarcoma cells in vivo. Furthermore, AbBmi-1 blocked NF-κB signaling and reduced MMP-9 expression. Furthermore, Bmi-1 promoted osteosarcoma tumor growth, whereas AbBmi-1 significantly inhibited osteosarcoma tumor growth in vitro and in vivo. Notably, AbBmi-1 decreased the percentages of Ki67-positive cells and terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells in tumors compared with Bmi-1-treated and PBS controls. Notably, MMP-9 and NF-κB expression were downregulated by treatment with AbBmi-1 in MG-63 osteosarcoma cells. In conclusion, the data provides evidence that AbBmi-1 inhibited the progression of osteosarcoma, suggesting that AbBmi-1 may be a novel anti-cancer agent through the inhibition of Bmi-1 via activating the NF-κB pathway in osteosarcoma. PMID:28983587

The WISSH quasars project. II. Giant star nurseries in hyper-luminous quasars

Science.gov (United States)

Duras, F.; Bongiorno, A.; Piconcelli, E.; Bianchi, S.; Pappalardo, C.; Valiante, R.; Bischetti, M.; Feruglio, C.; Martocchia, S.; Schneider, R.; Vietri, G.; Vignali, C.; Zappacosta, L.; La Franca, F.; Fiore, F.

2017-08-01

Context. Studying the coupling between the energy output produced by the central quasar and the host galaxy is fundamental to fully understand galaxy evolution. Quasar feedback is indeed supposed to dramatically affect the galaxy properties by depositing large amounts of energy and momentum into the interstellar medium (ISM). Aims: In order to gain further insights on this process, we study the spectral energy distributions (SEDs) of sources at the brightest end of the quasar luminosity function, for which the feedback mechanism is assumed to be at its maximum, given their high efficiency in driving powerful outflows. Methods: We modelled the rest-frame UV-to-far-IR SEDs of 16 WISE-SDSS Selected Hyper-luminous (WISSH) quasars at 1.8 code to account for the contribution of the quasar-related emission to the far-IR fluxes. Results: Most SEDs are well described by a standard combination of accretion disc plus torus and cold dust emission. However, about 30% of SEDs require an additional emission component in the near-IR, with temperatures peaking at 750 K, which indicates that a hotter dust component is present in these powerful quasars. We measure extreme values of both AGN bolometric luminosity (LBOL > 1047 erg/s) and star formation rate (up to 2000 M⊙/yr) based on the quasar-corrected, IR luminosity of the host galaxy. A new relation between quasar and star formation luminosity is derived (LSF ∝ L0.73QSO) by combining several Herschel-detected quasar samples from z 0 to 4. WISSH quasars have masses ( 108M⊙) and temperatures ( 50 K) of cold dust in agreement with those found for other high-z IR luminous quasars. Conclusions: Thanks to their extreme nuclear and star formation luminosities, the WISSH quasars are ideal targets to shed light on the feedback mechanism and its effect on the evolution of their host galaxies, as well as on the merger-induced scenario that is commonly assumed to explain these exceptional luminosities. Future observations will be

Study of luminous emissions associated to electron emissions in radiofrequency cavities; Etude des emissions lumineuses associees aux emissions electroniques dans les cavites hyperfrequences

Energy Technology Data Exchange (ETDEWEB)

Maissa, S

1996-11-26

This study investigates luminous emissions simultaneously to electron emissions and examines their features in order to better understand the field electron emission phenomenon. A RF cavity, operating at room temperature and in pulsed mode, joined to a sophisticated experimental apparatus has been especially developed. The electron and luminous emissions are investigated on cleaned or with metallic, graphitic and dielectric particles contaminated RF surfaces in order to study their influence on these phenomena. During the surface processing, unstable luminous spots glowing during one RF pulse are detected. Their apparition is promoted in the vicinity of the metallic particles or scratches. Two hypotheses could explain their origin: the presence of micro-plasmas associated to electronic explosive emission during processing or the thermal radiation of the melted metal during this emission. Stable luminous spots glowing during several RF pulses are also detected and appear to increase on RF surfaces contaminated with dielectric particles, leading to strong and explosive luminous emissions. Two interpretations are considered: the initiation of surface breakdowns on the dielectric particles or the heating by the RF field at temperatures sufficiently intense to provoke their thermal radiation then their explosion. Finally a superconducting cavity has been adapted to observe luminous spots, which differ from the former ones bu their star shape and could be associated to micro-plasmas, revealed by the starbursts observed on superconducting cavity walls. (author) 102 refs.

Immunohistochemical analysis of the mechanistic target of rapamycin and hypoxia signalling pathways in basal cell carcinoma and trichoepithelioma.

Directory of Open Access Journals (Sweden)

Tjinta Brinkhuizen

Full Text Available BACKGROUND: Basal cell carcinoma (BCC is the most common cancer in Caucasians. Trichoepithelioma (TE is a benign neoplasm that strongly resembles BCC. Both are hair follicle (HF tumours. HFs are hypoxic microenvironments, therefore we hypothesized that hypoxia-induced signalling pathways could be involved in BCC and TE as they are in other human malignancies. Hypoxia-inducible factor 1 (HIF1 and mechanistic/mammalian target of rapamycin (mTOR are key players in these pathways. OBJECTIVES: To determine whether HIF1/mTOR signalling is involved in BCC and TE. METHODS: We used immunohistochemical staining of formalin-fixed paraffin-embedded BCC (n = 45 and TE (n = 35 samples to assess activity of HIF1, mTORC1 and their most important target genes. The percentage positive tumour cells was assessed manually in a semi-quantitative manner and categorized (0%, 80%. RESULTS: Among 45 BCC and 35 TE examined, expression levels were respectively 81% and 57% (BNIP3, 73% and 75% (CAIX, 79% and 86% (GLUT1, 50% and 19% (HIF1α, 89% and 88% (pAKT, 55% and 61% (pS6, 15% and 25% (pMTOR, 44% and 63% (PHD2 and 44% and 49% (VEGF-A. CAIX, Glut1 and PHD2 expression levels were significantly higher in TE when only samples with at least 80% expression were included. CONCLUSIONS: HIF and mTORC1 signalling seems active in both BCC and TE. There are no appreciable differences between the two with respect to pathway activity. At this moment immunohistochemical analyses of HIF, mTORC1 and their target genes does not provide a reliable diagnostic tool for the discrimination of BCC and TE.

A stent for co-delivering paclitaxel and nitric oxide from abluminal and luminal surfaces: Preparation, surface characterization, and in vitro drug release studies

Energy Technology Data Exchange (ETDEWEB)

Gallo, Annemarie; Mani, Gopinath, E-mail: Gopinath.Mani@usd.edu

2013-08-15

Most drug-eluting stents currently available are coated with anti-proliferative drugs on both abluminal (toward blood vessel wall) and luminal (toward lumen) surfaces to prevent neointimal hyperplasia. While the abluminal delivery of anti-proliferative drugs is useful for controlling neointimal hyperplasia, the luminal delivery of such drugs impairs or prevents endothelialization which causes late stent thrombosis. This research is focused on developing a bidirectional dual drug-eluting stent to co-deliver an anti-proliferative agent (paclitaxel – PAT) and an endothelial cell promoting agent (nitric oxide – NO) from abluminal and luminal surfaces of the stent, respectively. Phosphonoacetic acid, a polymer-free drug delivery platform, was initially coated on the stents. Then, the PAT and NO donor drugs were co-coated on the abluminal and luminal stent surfaces, respectively. The co-coating of drugs was collectively confirmed by the surface characterization techniques such as Fourier transform infrared spectroscopy, scanning electron microscopy (SEM), 3D optical surface profilometry, and contact angle goniometry. SEM showed that the integrity of the co-coating of drugs was maintained without delamination or cracks formation occurring during the stent expansion experiments. In vitro drug release studies showed that the PAT was released from the abluminal stent surfaces in a biphasic manner, which is an initial burst followed by a slow and sustained release. The NO was burst released from the luminal stent surfaces. Thus, this study demonstrated the co-delivery of PAT and NO from abluminal and luminal stent surfaces, respectively. The stent developed in this study has potential applications in inhibiting neointimal hyperplasia as well as encouraging luminal endothelialization to prevent late stent thrombosis.

A stent for co-delivering paclitaxel and nitric oxide from abluminal and luminal surfaces: Preparation, surface characterization, and in vitro drug release studies

International Nuclear Information System (INIS)

Gallo, Annemarie; Mani, Gopinath

2013-01-01

Most drug-eluting stents currently available are coated with anti-proliferative drugs on both abluminal (toward blood vessel wall) and luminal (toward lumen) surfaces to prevent neointimal hyperplasia. While the abluminal delivery of anti-proliferative drugs is useful for controlling neointimal hyperplasia, the luminal delivery of such drugs impairs or prevents endothelialization which causes late stent thrombosis. This research is focused on developing a bidirectional dual drug-eluting stent to co-deliver an anti-proliferative agent (paclitaxel – PAT) and an endothelial cell promoting agent (nitric oxide – NO) from abluminal and luminal surfaces of the stent, respectively. Phosphonoacetic acid, a polymer-free drug delivery platform, was initially coated on the stents. Then, the PAT and NO donor drugs were co-coated on the abluminal and luminal stent surfaces, respectively. The co-coating of drugs was collectively confirmed by the surface characterization techniques such as Fourier transform infrared spectroscopy, scanning electron microscopy (SEM), 3D optical surface profilometry, and contact angle goniometry. SEM showed that the integrity of the co-coating of drugs was maintained without delamination or cracks formation occurring during the stent expansion experiments. In vitro drug release studies showed that the PAT was released from the abluminal stent surfaces in a biphasic manner, which is an initial burst followed by a slow and sustained release. The NO was burst released from the luminal stent surfaces. Thus, this study demonstrated the co-delivery of PAT and NO from abluminal and luminal stent surfaces, respectively. The stent developed in this study has potential applications in inhibiting neointimal hyperplasia as well as encouraging luminal endothelialization to prevent late stent thrombosis.

Selective response of human airway epithelia to luminal but not serosal solution hypertonicity. Possible role for proximal airway epithelia as an osmolality transducer

DEFF Research Database (Denmark)

Willumsen, Niels J.; Davis, C.W.; Boucher, R.C.

1994-01-01

exposure (10 min) to 430 mosM luminal solution elicited no regulation of any parameter. Optical measurements revealed a reduction in the thickness of preparations only in response to luminal hypertonic solutions. We conclude that (a) airway epithelial cells exhibit asymmetric water transport properties......- secretion; and (d) cell volume loss increases the resistance of the paracellular path. We speculate that these properties configure human nasal epithelium to behave as an osmotic sensor, transducing information about luminal solutions to the airway wall....

The most luminous type 2 Active Galactic Nuclei of the Swift/ BAT catalog : Are they different?

Science.gov (United States)

Baer, Rudolf Erik; Oh, Kyuseok; Koss, Michael; Wong, Ivy; Schawinski, Kevin

2018-01-01

We present an analysis of the most luminous obscured AGN of the Swift/BAT 70 month catalog, which is based on an all-sky survey in the 14 – 195 keV energy range. This survey identified 838 AGN. Excluding Blazars and AGN close ( |gb| BAT 70 month catalog and from a specific observation campaign in order to analyze the relationship of their luminosity to black hole mass and their Eddington ratios. We discuss whether these most luminous type 2 AGN have common characteristics, which differentiate them from all the type 2 AGN in the 70 month catalog.

Dual-energy index value of luminal air in fecal-tagging computed tomography colonography: findings and impact on electronic cleansing.

Science.gov (United States)

Cai, Wenli; Zhang, Da; Lee, June-Goo; Shirai, Yu; Kim, Se Hyung; Yoshida, Hiroyuki

2013-01-01

The purpose of our study was to measure the dual-energy index (DEI) value of colonic luminal air in both phantom and clinical fecal-tagging dual-energy computed tomography (CT) colonography (DE-CTC) images and to demonstrate its impact on dual-energy electronic cleansing. For the phantom study, a custom-ordered colon phantom was scanned by a dual-energy CT scanner (SOMATON Definition Flash; Siemens Healthcare, Forchheim, Germany) at two photon energies: 80 and 140 kVp. Before imaging, the phantom was filled with a 300-mL mixture of simulated fecal materials tagged by a nonionic iodinated contrast agent at three contrast concentrations: 20, 40, and 60 mg/mL. Ten regions-of-interest (ROIs) were randomly placed in each of the colonic luminal air, abdominal fat, bony structure, and tagged material in each scan. For the clinical study, 22 DE-CTC (80 and 140 kVp) patient cases were collected, who underwent a low-fiber, low-residue diet bowel preparation and orally administered iodine-based fecal tagging. Twenty ROIs were randomly placed in each of the colonic luminal air, abdominal fat, abdominal soft tissue, and tagged fecal material in each scan. For each ROI, the mean CT values in both 80- and 140-kVp images were measured, and then its DEI was calculated. In the phantom study, the mean DEI values of luminal air were 0.270, 0.298, 0.386, and 0.402 for the four groups of tagging conditions: no tagged material and tagged with three groups of contrast concentrations at 20, 40, and 60 mg/mL. In the clinical study, the mean DEI values were 0.341, -0.012, -0.002, and 0.188 for colonic luminal air, abdominal fat, abdominal soft tissue, and tagged fecal material, respectively. In our study, we observed that the DEI values of colonic luminal air in DE-CTC images (>0.10) were substantially higher than the theoretical value of 0.0063. In addition, the observed DEI values of colonic luminal air were significantly higher than those of soft tissue. These findings have an important

Signal interaction of Hedgehog/GLI and epidermal growth factor receptor signaling in cancer development

International Nuclear Information System (INIS)

Eberl, M.

2012-01-01

The subject of this PhD thesis is based on the cooperation of Hedgehog (HH)/GLI with epidermal growth factor receptor (EGFR) signaling synergistically promoting oncogenic transformation and cancer growth. In previous studies we have demonstrated that the HH/GLI and EGFR signaling pathways interact synergistically resulting not only in selective induction of HH/GLI-EGFR target genes, but also in the onset of oncogenic transformation and tumor formation (Kasper, Schnidar et al. 2006; Schnidar, Eberl et al. 2009). However, the molecular key mediators acting downstream of HH/GLI and EGFR signal cooperation were largely unknown and the in vivo evidence for the therapeutic relevance of HH/GLI and EGFR signal cooperation in HH-associated cancers was lacking. During my PhD thesis I could demonstrate that the integration of EGFR and HH/GLI signaling involves activation of RAS/MEK/ERK and JUN/AP1 signaling in response to EGFR activation. Furthermore I succeeded in identifying genes, including stem cell- (SOX2, SOX9), tumor growth- (JUN, TGFA, FGF19) and metastasis-associated genes (SPP1/osteopontin, CXCR4) that showed synergistic transcriptional activation by HH/GLI-EGFR signal integration. Importantly, I could demonstrate that these genes arrange themselves within a stable interdependent signaling network, which is required for in vivo growth of basal cell carcinoma (BCC) and tumor-initiating pancreatic cancer cells. These data validate EGFR signaling as additional drug target in HH/GLI driven cancers and provide new therapeutic strategies based on combined targeting of cooperative HH/GLI-EGFR signaling and selected downstream target genes (Eberl, Klingler et al. 2012). (author) [de

Effect of americium-241 on luminous bacteria. Role of peroxides

Energy Technology Data Exchange (ETDEWEB)

Alexandrova, M., E-mail: maka-alexandrova@rambler.r [Siberian Federal University, Svobodny 79, 660041 Krasnoyarsk (Russian Federation); Rozhko, T. [Siberian Federal University, Svobodny 79, 660041 Krasnoyarsk (Russian Federation); Vydryakova, G. [Institute of Biophysics SB RAS, Akademgorodok 50, 660036 Krasnoyarsk (Russian Federation); Kudryasheva, N. [Siberian Federal University, Svobodny 79, 660041 Krasnoyarsk (Russian Federation); Institute of Biophysics SB RAS, Akademgorodok 50, 660036 Krasnoyarsk (Russian Federation)

2011-04-15

The effect of americium-241 ({sup 241}Am), an alpha-emitting radionuclide of high specific activity, on luminous bacteria Photobacterium phosphoreum was studied. Traces of {sup 241}Am in nutrient media (0.16-6.67 kBq/L) suppressed the growth of bacteria, but enhanced luminescence intensity and quantum yield at room temperature. Lower temperature (4 {sup o}C) increased the time of bacterial luminescence and revealed a stage of bioluminescence inhibition after 150 h of bioluminescence registration start. The role of conditions of exposure the bacterial cells to the {sup 241}Am is discussed. The effect of {sup 241}Am on luminous bacteria was attributed to peroxide compounds generated in water solutions as secondary products of radioactive decay. Increase of peroxide concentration in {sup 241}Am solutions was demonstrated; and the similarity of {sup 241}Am and hydrogen peroxide effects on bacterial luminescence was revealed. The study provides a scientific basis for elaboration of bioluminescence-based assay to monitor radiotoxicity of alpha-emitting radionuclides in aquatic solutions. - Highlights: {yields} Am-241 in water solutions (A = 0.16-6.7 kBq/L) suppresses bacterial growth.{yields} Am-241 (A = 0.16-6.7 kBq/L) stimulate bacterial luminescence. {yields} Peroxides, secondary radiolysis products, cause increase of bacterial luminescence.

Modeling of luminance distribution in CAVE-type virtual reality systems

Science.gov (United States)

Meironke, Michał; Mazikowski, Adam

2017-08-01

At present, one of the most advanced virtual reality systems are CAVE-type (Cave Automatic Virtual Environment) installations. Such systems are usually consisted of four, five or six projection screens and in case of six screens arranged in form of a cube. Providing the user with a high level of immersion feeling in such systems is largely dependent of optical properties of the system. The modeling of physical phenomena plays nowadays a huge role in the most fields of science and technology. It allows to simulate work of device without a need to make any changes in the physical constructions. In this paper distribution of luminance in CAVE-type virtual reality systems were modelled. Calculations were performed for the model of 6-walled CAVE-type installation, based on Immersive 3D Visualization Laboratory, situated at the Faculty of Electronics, Telecommunications and Informatics at the Gdańsk University of Technology. Tests have been carried out for two different scattering distribution of the screen material in order to check how these characteristicinfluence on the luminance distribution of the whole CAVE. The basis assumption and simplification of modeled CAVE-type installation and results were presented. The brief discussion about the results and usefulness of developed model were also carried out.

An N-Terminal ER Export Signal Facilitates the Plasma Membrane Targeting of HCN1 Channels in Photoreceptors.

Science.gov (United States)

Pan, Yuan; Laird, Joseph G; Yamaguchi, David M; Baker, Sheila A

2015-06-01

Hyperpolarization-activated cyclic nucleotide-gated 1 (HCN1) channels are widely expressed in the retina. In photoreceptors, the hyperpolarization-activated current (Ih) carried by HCN1 is important for shaping the light response. It has been shown in multiple systems that trafficking HCN1 channels to specific compartments is key to their function. The localization of HCN1 in photoreceptors is concentrated in the plasma membrane of the inner segment (IS). The mechanisms controlling this localization are not understood. We previously identified a di-arginine endoplasmic reticulum (ER) retention motif that negatively regulates the surface targeting of HCN1. In this study, we sought to identify a forward trafficking signal that could counter the function of the ER retention signal. We studied trafficking of HCN1 and several mutants by imaging their subcellular localization in transgenic X. laevis photoreceptors. Velocity sedimentation was used to assay the assembly state of HCN1 channels. We found the HCN1 N-terminus can redirect a membrane reporter from outer segments (OS) to the plasma membrane of the IS. The sequence necessary for this behavior was mapped to a 20 amino acid region containing a leucine-based ER export motif. The ER export signal is necessary for forward trafficking but not channel oligomerization. Moreover, this ER export signal alone counteracted the di-arginine ER retention signal. We identified an ER export signal in HCN1 that functions with the ER retention signal to maintain equilibrium of HCN1 between the endomembrane system and the plasma membrane.

Missense mutations in IHH impair Indian Hedgehog signaling in C3H10T1/2 cells: Implications for brachydactyly type A1, and new targets for Hedgehog signaling.

Science.gov (United States)

Guo, Shengzhen; Zhou, Jian; Gao, Bo; Hu, Jianxin; Wang, Hongsheng; Meng, Junwei; Zhao, Xinzhi; Ma, Gang; Lin, Chuwen; Xiao, Yue; Tang, Wei; Zhu, Xuming; Cheah, Kathryn S E; Feng, Guoying; Chan, Danny; He, Lin

2010-01-01

Heterozygous missense mutations in IHH result in Brachydactyly type A1 (BDA1; OMIM 112500), a condition characterized by the shortening of digits due to hypoplasia/aplasia of the middle phalanx. Indian Hedgehog signaling regulates the proliferation and differentiation of chondrocytes and is essential for endochondral bone formation. Analyses of activated IHH signaling in C3H10T1/2 cells showed that three BDA1-associated mutations (p.E95K, p.D100E and p.E131K) severely impaired the induction of targets such as Ptch1 and Gli1. However, this was not a complete loss of function, suggesting that these mutations may affect the interaction with the receptor PTCH1 or its partners, with an impact on the induction potency. From comparative microarray expression analyses and quantitative real-time PCR, we identified three additional targets, Sostdc1, Penk1 and Igfbp5, which were also severely affected. Penk1 and Igfbp5 were confirmed to be regulated by GLI1, while the induction of Sostdc1 by IHH is independent of GLI1. SOSTDC1 is a BMP antagonist, and altered BMP signaling is known to affect digit formation. The role of Penk1 and Igfbp5 in skeletogenesis is not known. However, we have shown that both Penk1 and Igfbp5 are expressed in the interzone region of the developing joint of mouse digits, providing another link for a role for IHH signaling in the formation of the distal digits.

Normal and tumor-derived myoepithelial cells differ in their ability to interact with luminal breast epithelial cells for polarity and basement membrane deposition

Energy Technology Data Exchange (ETDEWEB)

Gudjonsson, Thorarinn; Ronnov-Jessen, Lone; Villadsen, Rene; Rank, Fritz; Bissell, Mina J.; Petersen, Ole William

2001-10-04

The signals that determine the correct polarity of breast epithelial structures in vivo are not understood. We have shown previously that luminal epithelial cells can be polarized when cultured within a reconstituted basement membrane gel. We reasoned that such cues in vivo may be given by myoepithelial cells. Accordingly, we used an assay where luminal epithelial cells are incorrectly polarized to test this hypothesis. We show that culturing human primary luminal epithelial cells within collagen-I gels leads to formation of structures with no lumina and with reverse polarity as judged by dual stainings for sialomucin, epithelial specific antigen or occludin. No basement membrane is deposited, and {beta}4-integrin staining is negative. Addition of purified human myoepithelial cells isolated from normal glands corrects the inverse polarity, and leads to formation of double-layered acini with central lumina. Among the laminins present in the human breast basement membrane (laminin-1, -5 and -10/11), laminin-1 was unique in its ability to substitute for myoepithelial cells in polarity reversal. Myoepithelial cells were purified also from four different breast cancer sources including a biphasic cell line. Three out of four samples either totally lacked the ability to interact with luminal epithelial cells, or conveyed only correction of polarity in a fraction of acini. This behavior was directly related to the ability of the tumor myoepithelial cells to produce {alpha}-1 chain of laminin. In vivo, breast carcinomas were either negative for laminin-1 (7/12 biopsies) or showed a focal, fragmented deposition of a less intensely stained basement membrane (5/12 biopsies). Dual staining with myoepithelial markers revealed that tumorassociated myoepithelial cells were either negative or weakly positive for expression of laminin-1, establishing a strong correlation between loss of laminin-1 and breast cancer. We conclude that the double-layered breast acinus may be

The galactic luminous supersoft X-ray source RXJ0925.7-4758 / MR ...

Indian Academy of Sciences (India)

Nandita Prodhani

2018-01-30

Jan 30, 2018 ... White dwarf; luminous supersoft X-ray source; luminosity; absorption edge. PACS Nos 97.80.Jp; 97.10.Ri; 98.35.Mp; 97.80.Fk. 1. Introduction. For the last few decades, Einstein observatory, Roent- gen Satellite (ROSAT), ASCA, CHANDRA, XMM-. Newton, SWIFT, SUZAKU and other ingenious devices.

Circumferential targeted renal sympathetic nerve denervation with preservation of the renal arterial wall using intra-luminal ultrasound

Science.gov (United States)

Roth, Austin; Coleman, Leslie; Sakakura, Kenichi; Ladich, Elena; Virmani, Renu

2015-03-01

An intra-luminal ultrasound catheter system (ReCor Medical's Paradise System) has been developed to provide circumferential denervation of the renal sympathetic nerves, while preserving the renal arterial intimal and medial layers, in order to treat hypertension. The Paradise System features a cylindrical non-focused ultrasound transducer centered within a balloon that circulates cooling fluid and that outputs a uniform circumferential energy pattern designed to ablate tissues located 1-6 mm from the arterial wall and protect tissues within 1 mm. RF power and cooling flow rate are controlled by the Paradise Generator which can energize transducers in the 8.5-9.5 MHz frequency range. Computer simulations and tissue-mimicking phantom models were used to develop the proper power, cooling flow rate and sonication duration settings to provide consistent tissue ablation for renal arteries ranging from 5-8 mm in diameter. The modulation of these three parameters allows for control over the near-field (border of lesion closest to arterial wall) and far-field (border of lesion farthest from arterial wall, consisting of the adventitial and peri-adventitial spaces) depths of the tissue lesion formed by the absorption of ultrasonic energy and conduction of heat. Porcine studies have confirmed the safety (protected intimal and medial layers) and effectiveness (ablation of 1-6 mm region) of the system and provided near-field and far-field depth data to correlate with bench and computer simulation models. The safety and effectiveness of the Paradise System, developed through computer model, bench and in vivo studies, has been demonstrated in human clinical studies.

Exploratory X-ray monitoring of luminous radio-quiet quasars at high redshift: Initial results

Energy Technology Data Exchange (ETDEWEB)

Shemmer, Ohad; Stein, Matthew S. [Department of Physics, University of North Texas, Denton, TX 76203 (United States); Brandt, W. N.; Schneider, Donald P. [Department of Astronomy and Astrophysics, The Pennsylvania State University, University Park, PA 16802 (United States); Paolillo, Maurizio [Dipartimento di Scienze Fisiche, Università Federico II di Napoli, via Cinthia 6, I-80126 Napoli (Italy); Kaspi, Shai [School of Physics and Astronomy and the Wise Observatory, Tel Aviv University, Tel Aviv 69978 (Israel); Vignali, Cristian [Dipartimento di Astronomia, Università degli studi di Bologna, via Ranzani 1, I-40127 Bologna (Italy); Lira, Paulina [Departamento de Astronomia, Universidad de Chile, Camino del Observatorio 1515, Santiago (Chile); Gibson, Robert R., E-mail: ohad@unt.edu [Department of Astronomy, University of Washington, Box 351580, Seattle, WA 98195 (United States)

2014-03-10

We present initial results from an exploratory X-ray monitoring project of two groups of comparably luminous radio-quiet quasars (RQQs). The first consists of four sources at 4.10 ≤ z ≤ 4.35, monitored by Chandra, and the second is a comparison sample of three sources at 1.33 ≤ z ≤ 2.74, monitored by Swift. Together with archival X-ray data, the total rest-frame temporal baseline spans ∼2-4 yr and ∼5-13 yr for the first and second group, respectively. Six of these sources show significant X-ray variability over rest-frame timescales of ∼10{sup 2}-10{sup 3} days; three of these also show significant X-ray variability on rest-frame timescales of ∼1-10 days. The X-ray variability properties of our variable sources are similar to those exhibited by nearby and far less luminous active galactic nuclei (AGNs). While we do not directly detect a trend of increasing X-ray variability with redshift, we do confirm previous reports of luminous AGNs exhibiting X-ray variability above that expected from their luminosities, based on simplistic extrapolation from lower luminosity sources. This result may be attributed to luminous sources at the highest redshifts having relatively high accretion rates. Complementary UV-optical monitoring of our sources shows that variations in their optical-X-ray spectral energy distribution are dominated by the X-ray variations. We confirm previous reports of X-ray spectral variations in one of our sources, HS 1700+6416, but do not detect such variations in any of our other sources in spite of X-ray flux variations of up to a factor of ∼4. This project is designed to provide a basic assessment of the X-ray variability properties of RQQs at the highest accessible redshifts that will serve as a benchmark for more systematic monitoring of such sources with future X-ray missions.

Luminous flux improvement of xenon fluorescent lamps by applying synchronized high-voltage pulse to the auxiliary external electrode

Energy Technology Data Exchange (ETDEWEB)

Motomura, Hideki; Oka, Kojiro; Sogabe, Toru; Jinno, Masafumi, E-mail: hmoto@mayu.ee.ehime-u.ac.jp [Department of Electrical and Electronic Engineering, Ehime University 3 Bunkyo-cho, Matsuyama, Ehime 790-8577 (Japan)

2011-06-08

As the environmental awareness of people becomes stronger, the demand for mercury-free light sources also becomes stronger. The authors have been developing cold cathode fluorescent lamps in which xenon gas is filled as an ultraviolet radiator instead of mercury. Previously the authors reported the luminous flux enhancement method using a grounded auxiliary external electrode (AEE). In this paper, in order to improve the luminous flux much more, a positive voltage pulse which was synchronized to the main driving negative voltage pulse was applied to the AEE. As a result, the maximum input power increased under which the positive column did not constrict and the luminous flux improved by 70% at the xenon filling pressure of 6.7 kPa. It is proved that the positive voltage pulse application to the AEE with the amplitude of more than 2 kV expands the positive column in the radial direction. It is attributed to the phenomenon that the residual ions and electrons, which are generated by dielectric barrier discharge between the AEE and the anode during the falling edge of the negative pulse to the cathode, spread the discharge path from the anode towards the AEE during the cold cathode discharge mode. By increasing the xenon filling pressure, luminous efficacy was improved to 25 lm W{sup -1}.

The application of unattended ground sensors to stationary targets

International Nuclear Information System (INIS)

Sleefe, G.E.; Peglow, S.; Hamrick, R.

1997-01-01

The unattended sensing of stationary (i.e. non-mobile) targets is important in applications ranging from counter-proliferation to law enforcement. With stationary targets, sources of seismic, acoustic, and electro-magnetic emissions can potentially be used to detect, identify, and locate the target. Stationary targets have considerably different sensing requirements than the traditional mobile-target unattended ground sensor applications. This paper presents the novel features and requirements of a system for sensing stationary targets. In particular, issues associated with long-listen time signal processing for signal detection, and array processing techniques for signal localization are presented. Example data and signal processing outputs from a stationary target will be used to illustrate these issues. The impact on sensor, electronic signal processing, battery subsystem, and communication requirements will also be discussed. The paper will conclude with a detailed comparison between mobile-target and stationary-target unattended ground sensor architectures

Genomic and phylogenetic characterization of luminous bacteria symbiotic with the deep-sea fish Chlorophthalmus albatrossis (Aulopiformes: Chlorophthalmidae).

Science.gov (United States)

Dunlap, Paul V; Ast, Jennifer C

2005-02-01

Bacteria forming light-organ symbiosis with deep-sea chlorophthalmid fishes (Aulopiformes: Chlorophthalmidae) are considered to belong to the species Photobacterium phosphoreum. The identification of these bacteria as P. phosphoreum, however, was based exclusively on phenotypic traits, which may not discriminate between phenetically similar but evolutionarily distinct luminous bacteria. Therefore, to test the species identification of chlorophthalmid symbionts, we carried out a genomotypic (repetitive element palindromic PCR genomic profiling) and phylogenetic analysis on strains isolated from the perirectal light organ of Chlorophthalmus albatrossis. Sequence analysis of the 16S rRNA gene of 10 strains from 5 fish specimens placed these bacteria in a cluster related to but phylogenetically distinct from the type strain of P. phosphoreum, ATCC 11040(T), and the type strain of Photobacterium iliopiscarium, ATCC 51760(T). Analysis of gyrB resolved the C. albatrossis strains as a strongly supported clade distinct from P. phosphoreum and P. iliopiscarium. Genomic profiling of 109 strains from the 5 C. albatrossis specimens revealed a high level of similarity among strains but allowed identification of genomotypically different types from each fish. Representatives of each type were then analyzed phylogenetically, using sequence of the luxABFE genes. As with gyrB, analysis of luxABFE resolved the C. albatrossis strains as a robustly supported clade distinct from P. phosphoreum. Furthermore, other strains of luminous bacteria reported as P. phosphoreum, i.e., NCIMB 844, from the skin of Merluccius capensis (Merlucciidae), NZ-11D, from the light organ of Nezumia aequalis (Macrouridae), and pjapo.1.1, from the light organ of Physiculus japonicus (Moridae), grouped phylogenetically by gyrB and luxABFE with the C. albatrossis strains, not with ATCC 11040(T). These results demonstrate that luminous bacteria symbiotic with C. albatrossis, together with certain other strains of

Active Luminous Blue Variables in the Large Magellanic Cloud

Energy Technology Data Exchange (ETDEWEB)

Walborn, Nolan R. [Space Telescope Science Institute, 3700 San Martin Drive, Baltimore, MD 21218 (United States); Gamen, Roberto C.; Lajús, Eduardo Fernández [Instituto de Astrofísica de La Plata, CONICET–UNLP and Facultad de Ciencias Astronómicas y Geofísicas, UNLP, Paseo del Bosque s/n, La Plata (Argentina); Morrell, Nidia I. [Las Campanas Observatory, Carnegie Observatories, Casilla 601, La Serena (Chile); Barbá, Rodolfo H. [Departamento de Física y Astronomía, Universidad de La Serena, Cisternas 1200 Norte, La Serena (Chile); Angeloni, Rodolfo, E-mail: walborn@stsci.edu, E-mail: rgamen@fcaglp.unlp.edu.ar, E-mail: eflajus@fcaglp.unlp.edu.ar, E-mail: nmorrell@lco.cl, E-mail: rbarba@dfuls.cl, E-mail: rangelon@gemini.edu [Gemini Observatory, Colina El Pino, Casilla 603, La Serena (Chile)

2017-07-01

We present extensive spectroscopic and photometric monitoring of two famous and currently highly active luminous blue variables (LBVs) in the Large Magellanic Cloud (LMC), together with more limited coverage of three further, lesser known members of the class. R127 was discovered as an Ofpe/WN9 star in the 1970s but entered a classical LBV outburst in or about 1980 that is still in progress, thus enlightening us about the minimum state of such objects. R71 is currently the most luminous star in the LMC and continues to provide surprises, such as the appearance of [Ca ii] emission lines, as its spectral type becomes unprecedentedly late. Most recently, R71 has developed inverse P Cyg profiles in many metal lines. The other objects are as follows: HDE 269582, now a “second R127” that has been followed from Ofpe/WN9 to A type in its current outburst; HDE 269216, which changed from late B in 2014 to AF in 2016, its first observed outburst; and R143 in the 30 Doradus outskirts. The light curves and spectroscopic transformations are correlated in remarkable detail and their extreme reproducibility is emphasized, both for a given object and among all of them. It is now believed that some LBVs proceed directly to core collapse. One of these unstable LMC objects may thus oblige in the near future, teaching us even more about the final stages of massive stellar evolution.

Active Luminous Blue Variables in the Large Magellanic Cloud

Science.gov (United States)

Walborn, Nolan R.; Gamen, Roberto C.; Morrell, Nidia I.; Barbá, Rodolfo H.; Fernández Lajús, Eduardo; Angeloni, Rodolfo

2017-07-01

We present extensive spectroscopic and photometric monitoring of two famous and currently highly active luminous blue variables (LBVs) in the Large Magellanic Cloud (LMC), together with more limited coverage of three further, lesser known members of the class. R127 was discovered as an Ofpe/WN9 star in the 1970s but entered a classical LBV outburst in or about 1980 that is still in progress, thus enlightening us about the minimum state of such objects. R71 is currently the most luminous star in the LMC and continues to provide surprises, such as the appearance of [Ca II] emission lines, as its spectral type becomes unprecedentedly late. Most recently, R71 has developed inverse P Cyg profiles in many metal lines. The other objects are as follows: HDE 269582, now a “second R127” that has been followed from Ofpe/WN9 to A type in its current outburst; HDE 269216, which changed from late B in 2014 to AF in 2016, its first observed outburst; and R143 in the 30 Doradus outskirts. The light curves and spectroscopic transformations are correlated in remarkable detail and their extreme reproducibility is emphasized, both for a given object and among all of them. It is now believed that some LBVs proceed directly to core collapse. One of these unstable LMC objects may thus oblige in the near future, teaching us even more about the final stages of massive stellar evolution.

Active Luminous Blue Variables in the Large Magellanic Cloud

International Nuclear Information System (INIS)

Walborn, Nolan R.; Gamen, Roberto C.; Lajús, Eduardo Fernández; Morrell, Nidia I.; Barbá, Rodolfo H.; Angeloni, Rodolfo

2017-01-01

We present extensive spectroscopic and photometric monitoring of two famous and currently highly active luminous blue variables (LBVs) in the Large Magellanic Cloud (LMC), together with more limited coverage of three further, lesser known members of the class. R127 was discovered as an Ofpe/WN9 star in the 1970s but entered a classical LBV outburst in or about 1980 that is still in progress, thus enlightening us about the minimum state of such objects. R71 is currently the most luminous star in the LMC and continues to provide surprises, such as the appearance of [Ca ii] emission lines, as its spectral type becomes unprecedentedly late. Most recently, R71 has developed inverse P Cyg profiles in many metal lines. The other objects are as follows: HDE 269582, now a “second R127” that has been followed from Ofpe/WN9 to A type in its current outburst; HDE 269216, which changed from late B in 2014 to AF in 2016, its first observed outburst; and R143 in the 30 Doradus outskirts. The light curves and spectroscopic transformations are correlated in remarkable detail and their extreme reproducibility is emphasized, both for a given object and among all of them. It is now believed that some LBVs proceed directly to core collapse. One of these unstable LMC objects may thus oblige in the near future, teaching us even more about the final stages of massive stellar evolution.

Linking express saccade occurance to stimulus properties and sensorimotor integration in the superior colliculus.

Science.gov (United States)

Marino, Robert A; Levy, Ron; Munoz, Douglas P

2015-08-01

Express saccades represent the fastest possible eye movements to visual targets with reaction times that approach minimum sensory-motor conduction delays. Previous work in monkeys has identified two specific neural signals in the superior colliculus (SC: a midbrain sensorimotor integration structure involved in gaze control) that are required to execute express saccades: 1) previsual activity consisting of a low-frequency increase in action potentials in sensory-motor neurons immediately before the arrival of a visual response; and 2) a transient visual-sensory response consisting of a high-frequency burst of action potentials in visually responsive neurons resulting from the appearance of a visual target stimulus. To better understand how these two neural signals interact to produce express saccades, we manipulated the arrival time and magnitude of visual responses in the SC by altering target luminance and we examined the corresponding influences on SC activity and express saccade generation. We recorded from saccade neurons with visual-, motor-, and previsual-related activity in the SC of monkeys performing the gap saccade task while target luminance was systematically varied between 0.001 and 42.5 cd/m(2) against a black background (∼0.0001 cd/m(2)). Our results demonstrated that 1) express saccade latencies were linked directly to the arrival time in the SC of visual responses produced by abruptly appearing visual stimuli; 2) express saccades were generated toward both dim and bright targets whenever sufficient previsual activity was present; and 3) target luminance altered the likelihood of producing an express saccade. When an express saccade was generated, visuomotor neurons increased their activity immediately before the arrival of the visual response in the SC and saccade initiation. Furthermore, the visual and motor responses of visuomotor neurons merged into a single burst of action potentials, while the visual response of visual-only neurons was

Linking express saccade occurance to stimulus properties and sensorimotor integration in the superior colliculus

Science.gov (United States)

Levy, Ron; Munoz, Douglas P.

2015-01-01

Express saccades represent the fastest possible eye movements to visual targets with reaction times that approach minimum sensory-motor conduction delays. Previous work in monkeys has identified two specific neural signals in the superior colliculus (SC: a midbrain sensorimotor integration structure involved in gaze control) that are required to execute express saccades: 1) previsual activity consisting of a low-frequency increase in action potentials in sensory-motor neurons immediately before the arrival of a visual response; and 2) a transient visual-sensory response consisting of a high-frequency burst of action potentials in visually responsive neurons resulting from the appearance of a visual target stimulus. To better understand how these two neural signals interact to produce express saccades, we manipulated the arrival time and magnitude of visual responses in the SC by altering target luminance and we examined the corresponding influences on SC activity and express saccade generation. We recorded from saccade neurons with visual-, motor-, and previsual-related activity in the SC of monkeys performing the gap saccade task while target luminance was systematically varied between 0.001 and 42.5 cd/m2 against a black background (∼0.0001 cd/m2). Our results demonstrated that 1) express saccade latencies were linked directly to the arrival time in the SC of visual responses produced by abruptly appearing visual stimuli; 2) express saccades were generated toward both dim and bright targets whenever sufficient previsual activity was present; and 3) target luminance altered the likelihood of producing an express saccade. When an express saccade was generated, visuomotor neurons increased their activity immediately before the arrival of the visual response in the SC and saccade initiation. Furthermore, the visual and motor responses of visuomotor neurons merged into a single burst of action potentials, while the visual response of visual-only neurons was

Investigating a multigene prognostic assay based on significant pathways for Luminal A breast cancer through gene expression profile analysis.

Science.gov (United States)

Gao, Haiyan; Yang, Mei; Zhang, Xiaolan

2018-04-01

The present study aimed to investigate potential recurrence-risk biomarkers based on significant pathways for Luminal A breast cancer through gene expression profile analysis. Initially, the gene expression profiles of Luminal A breast cancer patients were downloaded from The Cancer Genome Atlas database. The differentially expressed genes (DEGs) were identified using a Limma package and the hierarchical clustering analysis was conducted for the DEGs. In addition, the functional pathways were screened using Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses and rank ratio calculation. The multigene prognostic assay was exploited based on the statistically significant pathways and its prognostic function was tested using train set and verified using the gene expression data and survival data of Luminal A breast cancer patients downloaded from the Gene Expression Omnibus. A total of 300 DEGs were identified between good and poor outcome groups, including 176 upregulated genes and 124 downregulated genes. The DEGs may be used to effectively distinguish Luminal A samples with different prognoses verified by hierarchical clustering analysis. There were 9 pathways screened as significant pathways and a total of 18 DEGs involved in these 9 pathways were identified as prognostic biomarkers. According to the survival analysis and receiver operating characteristic curve, the obtained 18-gene prognostic assay exhibited good prognostic function with high sensitivity and specificity to both the train and test samples. In conclusion the 18-gene prognostic assay including the key genes, transcription factor 7-like 2, anterior parietal cortex and lymphocyte enhancer factor-1 may provide a new method for predicting outcomes and may be conducive to the promotion of precision medicine for Luminal A breast cancer.

Coating with luminal gut-constituents alters adherence of nanoparticles to intestinal epithelial cells

Directory of Open Access Journals (Sweden)

Heike Sinnecker

2014-12-01

Full Text Available Background: Anthropogenic nanoparticles (NPs have found their way into many goods of everyday life. Inhalation, ingestion and skin contact are potential routes for NPs to enter the body. In particular the digestive tract with its huge absorptive surface area provides a prime gateway for NP uptake. Considering that NPs are covered by luminal gut-constituents en route through the gastrointestinal tract, we wanted to know if such modifications have an influence on the interaction between NPs and enterocytes.Results: We investigated the consequences of a treatment with various luminal gut-constituents on the adherence of nanoparticles to intestinal epithelial cells. Carboxylated polystyrene particles 20, 100 and 200 nm in size represented our anthropogenic NPs, and differentiated Caco-2 cells served as model for mature enterocytes of the small intestine. Pretreatment with the proteins BSA and casein consistently reduced the adherence of all NPs to the cultured enterocytes, while incubation of NPs with meat extract had no obvious effect on particle adherence. In contrast, contact with intestinal fluid appeared to increase the particle-cell interaction of 20 and 100 nm NPs.Conclusion: Luminal gut-constituents may both attenuate and augment the adherence of NPs to cell surfaces. These effects appear to be dependent on the particle size as well as on the type of interacting protein. While some proteins will rather passivate particles towards cell attachment, possibly by increasing colloid stability or camouflaging attachment sites, certain components of intestinal fluid are capable to modify particle surfaces in such a way that interactions with cellular surface structures result in an increased binding.

High-Risk Premenopausal Luminal A Breast Cancer Patients Derive no Benefit from Adjuvant Cyclophosphamide-based Chemotherapy: Results from the DBCG77B Clinical Trial.

Science.gov (United States)

Nielsen, Torsten O; Jensen, Maj-Brit; Burugu, Samantha; Gao, Dongxia; Jørgensen, Charlotte L Tykjaer; Balslev, Eva; Ejlertsen, Bent

2017-02-15

Purpose: Luminal A breast cancers have better prognosis than other molecular subtypes. Luminal A cancers may also be insensitive to adjuvant chemotherapy, although there is little high-level evidence to confirm this concept. The primary hypothesis in this formal prospective-retrospective analysis was to assess interaction between subtype (Luminal A vs. other) and treatment (chemotherapy vs. not) for the primary endpoint (10-year invasive disease-free survival) of a breast cancer trial randomizing women to adjuvant chemotherapy, analyzed in multivariate Cox proportional hazards models using the Wald interaction test. Experimental Design: The Danish Breast Cancer Cooperative Group 77B clinical trial randomized 1,072 premenopausal women to no systematic treatment (control), levamisole, cyclophosphamide, or cyclophosphamide-methotrexate-fluorouracil arms. All arms included radiotherapy but no endocrine therapy. Researchers with no access to clinical data performed intrinsic subtype analysis on tissue microarrays using published immunohistochemical methods based on estrogen receptor, progesterone receptor, HER2, Ki67, and basal markers. Results: Patients ( n = 709) had tissue available; chemotherapy benefit in these patients was similar to the original trial (HR, 0.56). Immunohistochemistry classified 165 as Luminal A, 319 Luminal B, 58 HER2-enriched, and 82 core basal (among 91 triple-negative). Patients with Luminal A breast tumors did not benefit from chemotherapy [HR, 1.06; 95% confidence interval (CI), 0.53-2.14; P = 0.86], whereas patients with non-luminal A subtypes did (HR, 0.50; 95% CI, 0.38-0.66; P benefit from adjuvant cyclophosphamide-based chemotherapy. Clin Cancer Res; 23(4); 946-53. ©2016 AACR . ©2016 American Association for Cancer Research.

Targeting Wnt Pathways in Disease

Science.gov (United States)

Zimmerman, Zachary F.; Moon, Randall T.

2012-01-01

Wnt-mediated signal transduction pathways have long been recognized for their roles in regulating embryonic development, and have more recently been linked to cancer, neurologic diseases, inflammatory diseases, and disorders of endocrine function and bone metabolism in adults. Although therapies targeting Wnt signaling are attractive in theory, in practice it has been difficult to obtain specific therapeutics because many components of Wnt signaling pathways are also involved in other cellular processes, thereby reducing the specificity of candidate therapeutics. New technologies, and advances in understanding the mechanisms of Wnt signaling, have improved our understanding of the nuances of Wnt signaling and are leading to promising new strategies to target Wnt signaling pathways. PMID:23001988

A Recombinant Secondary Antibody Mimic as a Target-specific Signal Amplifier and an Antibody Immobilizer in Immunoassays.

Science.gov (United States)

Min, Junseon; Song, Eun Kyung; Kim, Hansol; Kim, Kyoung Taek; Park, Tae Joo; Kang, Sebyung

2016-04-11

We construct a novel recombinant secondary antibody mimic, GST-ABD, which can bind to the Fc regions of target-bound primary antibodies and acquire multiple HRPs simultaneously. We produce it in tenth of mg quantities with a bacterial overexpression system and simple purification procedures, significantly reducing the manufacturing cost and time without the use of animals. GST-ABD is effectively conjugated with 3 HRPs per molecule on an average and selectively bind to the Fc region of primary antibodies derived from three different species (mouse, rabbit, and rat). HRP-conjugated GST-ABD (HRP-GST-ABD) is successfully used as an alternative to secondary antibodies to amplify target-specific signals in both ELISA and immunohistochemistry regardless of the target molecules and origin of primary antibodies used. GST-ABD also successfully serves as an anchoring adaptor on the surface of GSH-coated plates for immobilizing antigen-capturing antibodies in an orientation-controlled manner for sandwich-type indirect ELISA through simple molecular recognition without any complicated chemical modification.

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

Science.gov (United States)

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

2018-04-01

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

Therapeutic Targeting of Redox Signaling in Myofibroblast Differentiation and Age-Related Fibrotic Disease

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Natalie Sampson

2012-01-01

Full Text Available Myofibroblast activation plays a central role during normal wound healing. Whereas insufficient myofibroblast activation impairs wound healing, excessive myofibroblast activation promotes fibrosis in diverse tissues (including benign prostatic hyperplasia, BPH leading to organ dysfunction and also promotes a stromal response that supports tumor progression. The incidence of impaired wound healing, tissue fibrosis, BPH, and certain cancers strongly increases with age. This paper summarizes findings from in vitro fibroblast-to-myofibroblast differentiation systems that serve as cellular models to study fibrogenesis of diverse tissues. Supported by substantial in vivo data, a large body of evidence indicates that myofibroblast differentiation induced by the profibrotic cytokine transforming growth factor beta is driven by a prooxidant shift in redox homeostasis due to elevated production of NADPH oxidase 4 (NOX4-derived hydrogen peroxide and supported by concomitant decreases in nitric oxide/cGMP signaling and reactive oxygen species (ROS scavenging enzymes. Fibroblast-to-myofibroblast differentiation can be inhibited and reversed by restoring redox homeostasis using antioxidants or NOX4 inactivation as well as enhancing nitric oxide/cGMP signaling via activation of soluble guanylyl cyclases or inhibition of phosphodiesterases. Current evidence indicates the therapeutic potential of targeting the prooxidant shift in redox homeostasis for the treatment of age-related diseases associated with myofibroblast dysregulation.

Psychophysical Measurements of Luminance Contrast Sensitivity and Color Discrimination with Transparent and Blue-Light Filter Intraocular Lenses.

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da Costa, Marcelo Fernandes; Júnior, Augusto Paranhos; Lottenberg, Claudio Luiz; Castro, Leonardo Cunha; Ventura, Dora Fix

2017-12-01

The purpose of this study was to measure luminance contrast sensitivity and color vision thresholdfs in normal subjects using a blue light filter lens and transparent intraocular lens material. Monocular luminance grating contrast sensitivity was measured with Psycho for Windows (version 2.36; Cambridge Research Systems) at 3.0, 6.0, 12.0, 20.0, and 30.0 cycles per degree of visual angle (cpd) in 15 normal subjects (eight female), with a mean age of 21.6 years (SD = 3.8 years). Chromatic discrimination was assessed with the Cambridge colour test (CCT) along the protan, deutan, and tritan color confusion axes. Both tests were performed in a darkened room under two situations: with a transparent lens and with blue light filter lens. Subjective impressions were taken by subjects regarding their visual experience under both conditions. No difference was found between the luminance contrast sensitivity measured with transparent and blue light filter. However, 13/15 (87%) of the subjects reported more comfortable vision with the blue filter. In the color vision test, tritan thresholds were significantly higher for the blue filter compared with the transparent filter (p = 0.003). For protan and deutan thresholds no differences were found. Blue-yellow color vision is impaired with the blue light filter, and no impairment occurs with the transparent filter. No significant differences in thresholds were found in the luminance contrast sensitivity comparing the blue light and transparent filters. The impact of short wavelength light filtering on intrinsically photosensitive retinal ganglion cells is also discussed.

Specific protein supplementation using soya, casein or whey differentially affects regional gut growth and luminal growth factor bioactivity in rats; implications for the treatment of gut injury and stimulating repair.

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Marchbank, Tania; Mandir, Nikki; Calnan, Denis; Goodlad, Robert A; Podas, Theo; Playford, Raymond J

2018-01-24

Modulation of regional growth within specific segments of the bowel may have clinical value for several gastrointestinal conditions. We therefore examined the effects of different dietary protein sources on regional gut growth and luminal growth factor bioactivity as potential therapies. Rats were fed for 14 days on isonitrogenous and isocaloric diets comprising elemental diet (ED) alone (which is known to cause gut atrophy), ED supplemented with casein or whey or a soya protein-rich feed. Effects on regional gut growth and intraluminal growth factor activity were then determined. Despite calorie intake being similar in all groups, soya rich feed caused 20% extra total body weight gain. Stomach weight was highest on soya and casein diets. Soya enhanced diet caused greatest increase in small intestinal weight and preserved luminal growth factor activity at levels sufficient to increase proliferation in vitro. Regional small intestinal proliferation was highest in proximal segment in ED fed animals whereas distal small intestine proliferation was greater in soya fed animals. Colonic weight and proliferation throughout the colon was higher in animals receiving soya or whey supplemented feeds. We conclude that specific protein supplementation with either soya, casein or whey may be beneficial to rest or increase growth in different regions of the bowel through mechanisms that include differentially affecting luminal growth factor bioactivity. These results have implications for targeting specific regions of the bowel for conditions such as Crohn's disease and chemotherapy.

PDK1 in NF-κB signaling is a target of Xanthium strumarium methanolic extract-mediated anti-inflammatory activities.

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Hossen, Muhammad Jahangir; Cho, Jae Youl; Kim, Daewon

2016-08-22

Xanthium strumarium L. (Asteraceae) has traditionally been used to treat bacterial infections, nasal sinusitis, urticaria, arthritis, chronic bronchitis and rhinitis, allergic rhinitis, edema, lumbago, and other ailments. However, the molecular mechanisms by which this plant exerts its anti-inflammatory effects are poorly characterized. Here we studied the immunopharmacological activities of the methanolic extract of the aerial parts of this plant (Xs-ME) and validated its pharmacological targets. To evaluate the anti-inflammatory activity of Xs-ME, we employed lipopolysaccharide (LPS)-treated macrophages and an HCl/EtOH-induced mouse model of gastritis. We also used HPLC to identify the potentially active anti-inflammatory components of this extract. The molecular mechanisms of its anti-inflammatory activity were studied by kinase assays, reporter gene assays, immunoprecipitation analysis, and overexpression of target enzymes. The production of nitric oxide (NO) and prostaglandin E2 (PGE2) were both suppressed by Xs-ME. Moreover, orally administered Xs-ME ameliorated HCl/EtOH-induced gastric lesions. Furthermore, this extract downregulated the expression of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 and reduced the nuclear levels of NF-κB. Signaling events upstream of NF-κB translocation, such as phosphorylation of AKT and the formation of PDK1-AKT signaling complexes, were also inhibited by Xs-ME. Moreover, Xs-ME suppressed the enzymatic activity of PDK1. Additionally, PDK1-induced luciferase activity and Akt phosphorylation were both inhibited by Xs-ME. We also identified the polyphenol resveratrol as a likely active anti-inflammatory component in Xs-ME that targets PDK1. Xs-ME exerts anti-inflammatory activity in vitro and in vivo by inhibiting PDK1 kinase activity and blocking signaling to its downstream transcription factor, NF-κB. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Identification of lncRNA FAM83H-AS1 as a novel prognostic marker in luminal subtype breast cancer

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Yang F

2016-11-01

Full Text Available Fan Yang, Shi-Xu Lv, Lin Lv, Ye-Huan Liu, Si-Yang Dong, Zhi-Han Yao, Xuan-xuan Dai, Xiao-Hua Zhang, Ou-Chen Wang Department of Surgical Oncology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China Background: Luminal subtype breast cancer accounts for a predominant number of breast cancers. Considering the heterogeneity of the disease, it is urgent to develop novel biomarkers to improve risk stratification and optimize therapy choices. Long non-coding RNA (lncRNA represents an emerging and understudied class of transcripts that play a significant role in cancer biology. Growing knowledge of cancer-associated lncRNAs contributes to the development of molecular markers for prognosis evaluation and gene therapy.Materials and methods: Three pairs of primary luminal subtype breast cancer tissues and adjacent non-cancerous tissues were collected and sequenced. EBseq algorithm was used to identify differentially expressed lncRNAs. RNA sequencing data from The Cancer Genome Atlas (TCGA database were used to validate the robustness of our RNA-seq results. Kaplan–Meier and Cox regression analyses were utilized to assess the association between the lncRNAs and overall survival of patients in TCGA cohort.Results: A total of 796 lncRNAs were significantly dysregulated in luminal subtype breast cancer, including 436 upregulated and 360 downregulated lncRNAs. Among them, FAM83H antisense RNA 1 (FAM83H-AS1 was the most upregulated lncRNA, whereas GSN antisense RNA 1 (GSN-AS1 was the most downregulated lncRNA. Moreover, we proved that the high expression level of FAM83H-AS1 indicated unfavorable prognosis not only in luminal subtype breast cancer but also in all subtype breast cancers. To the best of our knowledge, this is the first report indicating that FAM83H-AS1 was involved in luminal subtype breast cancer and was an independent prognostic indicator.Conclusion: Our study provides a rich resource

Targeting Glutamatergic Signaling and the PI3 Kinase Pathway to Halt Melanoma Progression

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Stephen A. Rosenberg

2015-02-01

Full Text Available Our group has previously reported that the majority of human melanomas (>60% express the metabotropic glutamate receptor 1 (GRM1 and that the glutamate release inhibitor riluzole, a drug currently used to treat amyotrophic lateral sclerosis, can induce apoptosis in GRM1-expressing melanoma cells. Our group previously reported that in vitro riluzole treatment reduces cell growth in three-dimensional (3D soft agar colony assays by 80% in cells with wildtype phosphoinositide 3-kinase (PI3K pathway activation. However, melanoma cell lines harboring constitutive activating mutations of the PI3K pathway (PTEN and NRAS mutations showed only a 35% to 40% decrease in colony formation in soft agar in the presence of riluzole. In this study, we have continued our preclinical studies of riluzole and its effect on melanoma cells alone and in combination with inhibitors of the PI3 kinase pathway: the AKT inhibitor, API-2, and the mammalian target of rapamycin (mTOR inhibitor, rapamycin. We modeled these combinatorial therapies on various melanoma cell lines in 3D and 2D systems and in vivo. Riluzole combined with mTOR inhibition is more effective at halting melanoma anchorage-independent growth and xenograft tumor progression than either agent alone. PI3K signaling changes associated with this combinatorial treatment shows that 3D (nanoculture modeling of cell signaling more closely resembles in vivo signaling than monolayer models. Riluzole combined with mTOR inhibition is effective at halting tumor cell progression independent of BRAF mutational status. This makes this combinatorial therapy a potentially viable alternative for metastatic melanoma patients who are BRAF WT and are therefore ineligible for vemurafenib therapy.

A longitudinal study of perceptual grouping by proximity, luminance and shape in infants at two, four and six months

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Farran, E. K.; Brown, J. H.; Cole, V. L.; Houston-Price, C.; Karmiloff-Smith, A.

2008-01-01

Grouping by luminance and shape similarity has previously been demonstrated in neonates and at 4 months, respectively. By contrast, grouping by proximity has hitherto not been investigated in infancy. This is also the first study to chart the developmental emergence of perceptual grouping longitudinally. Sixty-one infants were presented with a matrix of local stimuli grouped horizontally or vertically by luminance, shape or proximity at 2, 4, and 6 months. Infants were exposed to each set of ...

miR-958 inhibits Toll signaling and Drosomycin expression via direct targeting of Toll and Dif in Drosophila melanogaster.

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Li, Shengjie; Li, Yao; Shen, Li; Jin, Ping; Chen, Liming; Ma, Fei

2017-02-01

Drosophila melanogaster is widely used as a model system to study innate immunity and signaling pathways related to innate immunity, including the Toll signaling pathway. Although this pathway is well studied, the precise mechanisms of posttranscriptional regulation of key components of the Toll signaling pathway by microRNAs (miRNAs) remain obscure. In this study, we used an in silico strategy in combination with the Gal80 ts -Gal4 driver system to identify microRNA-958 (miR-958) as a candidate Toll pathway regulating miRNA in Drosophila We report that overexpression of miR-958 significantly reduces the expression of Drosomycin, a key antimicrobial peptide involved in Toll signaling and the innate immune response. We further demonstrate in vitro and in vivo that miR-958 targets the Toll and Dif genes, key components of the Toll signaling pathway, to negatively regulate Drosomycin expression. In addition, a miR-958 sponge rescued the expression of Toll and Dif, resulting in increased expression of Drosomycin. These results, not only revealed a novel function and modulation pattern of miR-958, but also provided a new insight into the underlying molecular mechanisms of Toll signaling in regulation of innate immunity. Copyright © 2017 the American Physiological Society.

Kinetics on Demand Is a Simple Mathematical Solution that Fits Recorded Caffeine-Induced Luminal SR Ca2+ Changes in Smooth Muscle Cells.

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Norma C Perez-Rosas

Full Text Available The process of Ca2+ release from sarcoplasmic reticulum (SR comprises 4 phases in smooth muscle cells. Phase 1 is characterized by a large increase of the intracellular Ca2+ concentration ([Ca2+]i with a minimal reduction of the free luminal SR [Ca2+] ([Ca2+]FSR. Importantly, active SR Ca2+ ATPases (SERCA pumps are necessary for phase 1 to occur. This situation cannot be explained by the standard kinetics that involves a fixed amount of luminal Ca2+ binding sites. A new mathematical model was developed that assumes an increasing SR Ca2+ buffering capacity in response to an increase of the luminal SR [Ca2+] that is called Kinetics-on-Demand (KonD model. This approach can explain both phase 1 and the refractory period associated with a recovered [Ca2+]FSR. Additionally, our data suggest that active SERCA pumps are a requisite for KonD to be functional; otherwise luminal SR Ca2+ binding proteins switch to standard kinetics. The importance of KonD Ca2+ binding properties is twofold: a more efficient Ca2+ release process and that [Ca2+]FSR and Ca2+-bound to SR proteins ([Ca2+]BSR can be regulated separately allowing for Ca2+ release to occur (provided by Ca2+-bound to luminal Ca2+ binding proteins without an initial reduction of the [Ca2+]FSR.

A targeted constitutive mutation in the APC tumor suppressor gene underlies mammary but not intestinal tumorigenesis.

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Claudia Gaspar

2009-07-01

Full Text Available Germline mutations in the adenomatous polyposis coli (APC gene are responsible for familial adenomatous polyposis (FAP, an autosomal dominant hereditary predisposition to the development of multiple colorectal adenomas and of a broad spectrum of extra-intestinal tumors. Moreover, somatic APC mutations play a rate-limiting and initiating role in the majority of sporadic colorectal cancers. Notwithstanding its multifunctional nature, the main tumor suppressing activity of the APC gene resides in its ability to regulate Wnt/beta-catenin signaling. Notably, genotype-phenotype correlations have been established at the APC gene between the length and stability of the truncated proteins encoded by different mutant alleles, the corresponding levels of Wnt/beta-catenin signaling activity they encode for, and the incidence and distribution of intestinal and extra-intestinal tumors. Here, we report a novel mouse model, Apc1572T, obtained by targeting a truncated mutation at codon 1572 in the endogenous Apc gene. This hypomorphic mutant allele results in intermediate levels of Wnt/beta-catenin signaling activation when compared with other Apc mutations associated with multifocal intestinal tumors. Notwithstanding the constitutive nature of the mutation, Apc(+/1572T mice have no predisposition to intestinal cancer but develop multifocal mammary adenocarcinomas and subsequent pulmonary metastases in both genders. The histology of the Apc1572T primary mammary tumours is highly heterogeneous with luminal, myoepithelial, and squamous lineages and is reminiscent of metaplastic carcinoma of the breast in humans. The striking phenotype of Apc(+/1572T mice suggests that specific dosages of Wnt/beta-catenin signaling activity differentially affect tissue homeostasis and initiate tumorigenesis in an organ-specific fashion.

Shock waves in luminous early-type stars

International Nuclear Information System (INIS)

Castor, J.I.

1986-01-01

Shock waves that occur in stellar atmospheres have their origin in some hydrodynamic instability of the atmosphere itself or of the stellar interior. In luminous early-type stars these two possibilities are represented by shocks due to an unstable radiatively-accelerated wind, and to shocks generated by the non-radial pulsations known to be present in many or most OB stars. This review is concerned with the structure and development of the shocks in these two cases, and especially with the mass loss that may be due specifically to the shocks. Pulsation-produced shocks are found to be very unfavorable for causing mass loss, owing to the great radiation efficiency that allows them to remain isothermal. The situation regarding radiatively-driven shocks remains unclear, awaiting detailed hydrodynamics calculations. 20 refs., 2 figs

An Epstein-Barr Virus MicroRNA Blocks Interleukin-1 (IL-1) Signaling by Targeting IL-1 Receptor 1.

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Skinner, Camille M; Ivanov, Nikita S; Barr, Sarah A; Chen, Yan; Skalsky, Rebecca L

2017-11-01

Epstein-Barr virus (EBV) encodes >44 viral microRNAs (miRNAs) that are differentially expressed throughout infection, can be detected in Epstein-Barr virus (EBV)-positive tumors, and manipulate several biological processes, including cell proliferation, apoptosis, and immune responses. Here, we show that EBV BHRF1-2 miRNAs block NF-κB activation following treatment with proinflammatory cytokines, specifically interleukin-1β (IL-1β). Analysis of EBV PAR-CLIP miRNA targetome data sets combined with pathway analysis revealed multiple BHRF1-2 miRNA targets involved in interleukin signaling pathways. By further analyzing changes in cellular gene expression patterns, we identified the IL-1 receptor 1 (IL1R1) as a direct target of miR-BHRF1-2-5p. Targeting the IL1R1 3' untranslated region (UTR) by EBV miR-BHRF1-2-5p was confirmed using 3'-UTR luciferase reporter assays and Western blot assays. Manipulation of EBV BHRF1-2 miRNA activity in latently infected B cells altered steady-state cytokine levels and disrupted IL-1β responsiveness. These studies demonstrate functionally relevant BHRF1-2 miRNA interactions during EBV infection, which is an important step in understanding their roles in pathogenesis. IMPORTANCE IL-1 signaling plays an important role in inflammation and early activation of host innate immune responses following virus infection. Here, we demonstrate that a viral miRNA downregulates the IL-1 receptor 1 during EBV infection, which consequently alters the responsiveness of cells to IL-1 stimuli and changes the cytokine expression levels within infected cell populations. We postulate that this viral miRNA activity not only disrupts IL-1 autocrine and paracrine signaling loops that can alert effector cells to sites of infection but also provides a survival advantage by dampening excessive inflammation that may be detrimental to the infected cell. Copyright © 2017 American Society for Microbiology.

Pharmacological Targeting SHP-1-STAT3 Signaling Is a Promising Therapeutic Approach for the Treatment of Colorectal Cancer

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Li-Ching Fan

2015-09-01

Full Text Available STAT3 activation is associated with poor prognosis in human colorectal cancer (CRC. Our previous data demonstrated that regorafenib (Stivarga is a pharmacological agonist of SH2 domain-containing phosphatase 1 (SHP-1 that enhances SHP-1 activity and induces apoptosis by targeting STAT3 signals in CRC. This study aimed to find a therapeutic drug that is more effective than regorafenib for CRC treatment. Here, we showed that SC-43 was more effective than regorafenib at inducing apoptosis in vitro and suppressing tumorigenesis in vivo. SC-43 significantly increased SHP-1 activity, downregulated p-STAT3Tyr705 level, and induced apoptosis in CRC cells. An SHP-1 inhibitor or knockdown of SHP-1 by siRNA both significantly rescued the SC-43–induced apoptosis and decreased p-STAT3Tyr705 level. Conversely, SHP-1 overexpression increased the effects of SC-43 on apoptosis and p-STAT3Tyr705 level. These data suggest that SC-43–induced apoptosis mediated through the loss of p-STAT3Tyr705 was dependent on SHP-1 function. Importantly, SC-43–enhanced SHP-1 activity was because of the docking potential of SC-43, which relieved the autoinhibited N-SH2 domain of SHP-1 and inhibited p-STAT3Tyr705 signals. Importantly, we observed that a significant negative correlation existed between SHP-1 and p-STAT3Tyr705expression in CRC patients (P = .038. Patients with strong SHP-1 and weak p-STAT3Tyr705 expression had significantly higher overall survival compared with patients with weak SHP-1 and strong p-STAT3Tyr705 expression (P = .029. In conclusion, SHP-1 is suitable to be a useful prognostic marker and a pharmacological target for CRC treatment. Targeting SHP-1-STAT3 signaling by SC-43 may serve as a promising pharmacotherapy for CRC.