Interaction Between the Broad-Lined Type Ic Supernova 2012ap and Carriers of Diffuse Interstellar Bands

NASA Technical Reports Server (NTRS)

Milisavljevic, Dan; Margutti, Raffaella; Crabtree, Kyle N.; Foster, Jonathan B.; Soderberg, Alicia M.; Fesen, Robert A.; Parrent, Jerod T.; Sanders, Nathan E.; Drout, Maria R.; Kamble, Atish;

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

Liu, Yu-Qian; Modjaz, Maryam; Bianco, Federica B., E-mail: YL1260@nyu.edu, E-mail: mmodjaz@nyu.edu

Super-luminous supernovae (SLSNe) are tremendously luminous explosions whose power sources and progenitors are highly debated. Broad-lined SNe Ic (SNe Ic-bl) are the only type of SNe that are connected with long-duration gamma-ray bursts (GRBs). Studying the spectral similarity and difference between the populations of hydrogen-poor SLSNe (SLSNe Ic) and of hydrogen-poor stripped-envelope core-collapse SNe, in particular SNe Ic and SNe Ic-bl, can provide crucial observations to test predictions of theories based on various power source models and progenitor models. In this paper, we collected all of the published optical spectra of 32 SLSNe Ic, 21 SNe Ic-bl, as well asmore » 17 SNe Ic, quantified their spectral features, constructed average spectra, and compared them in a systematic way using new tools we have developed. We find that SLSNe Ic and SNe Ic-bl, including those connected with GRBs, have comparable widths for their spectral features and average absorption velocities at all phases. Thus, our findings strengthen the connection between SLSNe Ic and GRBs. In particular, SLSNe Ic have average Fe ii λ 5169 absorption velocities of −15,000 ± 2600 km s{sup −1} at 10 days after peak, which are higher than those of SNe Ic by ∼7000 km s{sup −1} on average. SLSNe Ic also have significantly broader Fe ii λ 5169 lines than SNe Ic. Moreover, we find that such high absorption and width velocities of SLSNe Ic may be hard to explain with the interaction model, and none of the 13 SLSNe Ic with measured absorption velocities spanning over 10 days has a convincing flat velocity evolution, which is inconsistent with the magnetar model in one dimension. Lastly, we compare SN 2011kl, the first SN connected with an ultra-long GRB, with the mean spectrum of SLSNe Ic and of SNe Ic-bl.« less

On the origin of gamma-rays in Fermi blazars: beyondthe broad-line region

NASA Astrophysics Data System (ADS)

Costamante, L.; Cutini, S.; Tosti, G.; Antolini, E.; Tramacere, A.

2018-07-01

The gamma-ray emission in broad-line blazars is generally explained as inverse Compton (IC) radiation of relativistic electrons in the jet scattering optical-UV photons from the broad-line region (BLR), the so-called BLR external Compton (EC) scenario. We test this scenario on the Fermi gamma-ray spectra of 106 broad-line blazars detected with the highest significance or largest BLR, by looking for cut-off signatures at high energies compatible with γ-γ interactions with BLR photons. We do not find evidence for the expected BLR absorption. For 2/3 of the sources, we can exclude any significant absorption (τmax < 1), while for the remaining 1/3 the possible absorption is constrained to be 1.5-2 orders of magnitude lower than expected. This result holds also dividing the spectra in high- and low-flux states, and for powerful blazars with large BLR. Only 1 object out of 10 seems compatible with substantial attenuation (τmax > 5). We conclude that for 9 out of 10 objects, the jet does not interact with BLR photons. Gamma-rays seem either produced outside the BLR most of the time, or the BLR is ˜100 × larger than given by reverberation mapping. This means that (i) EC on BLR photons is disfavoured as the main gamma-ray mechanism, versus IC on IR photons from the torus or synchrotron self-Compton; (ii) the Fermi gamma-ray spectrum is mostly intrinsic, determined by the interaction of the particle distribution with the seed-photon spectrum; and (iii) without suppression by the BLR, broad-line blazars can become copious emitters above 100 GeV, as demonstrated by 3C 454.3. We expect the CTA sky to be much richer of broad-line blazars than previously thought.

On the origin of gamma rays in Fermi blazars: beyond the broad line region.

NASA Astrophysics Data System (ADS)

Costamante, L.; Cutini, S.; Tosti, G.; Antolini, E.; Tramacere, A.

2018-05-01

The gamma-ray emission in broad-line blazars is generally explained as inverse Compton (IC) radiation of relativistic electrons in the jet scattering optical-UV photons from the Broad Line Region (BLR), the so-called BLR External Compton scenario. We test this scenario on the Fermi gamma-ray spectra of 106 broad-line blazars detected with the highest significance or largest BLR, by looking for cut-off signatures at high energies compatible with γ-γ interactions with BLR photons. We do not find evidence for the expected BLR absorption. For 2/3 of the sources, we can exclude any significant absorption (τmax < 1), while for the remaining 1/3 the possible absorption is constrained to be 1.5-2 orders of magnitude lower than expected. This result holds also dividing the spectra in high and low-flux states, and for powerful blazars with large BLR. Only 1 object out of 10 seems compatible with substantial attenuation (τmax > 5). We conclude that for 9 out of 10 objects, the jet does not interact with BLR photons. Gamma-rays seem either produced outside the BLR most of the time, or the BLR is ˜100 × larger than given by reverberation mapping. This means that i) External Compton on BLR photons is disfavoured as the main gamma-ray mechanism, vs IC on IR photons from the torus or synchrotron self-Compton; ii) the Fermi gamma-ray spectrum is mostly intrinsic, determined by the interaction of the particle distribution with the seed-photons spectrum; iii) without suppression by the BLR, broad-line blazars can become copious emitters above 100 GeV, as demonstrated by 3C 454.3. We expect the CTA sky to be much richer of broad-line blazars than previously thought.

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

Xu, D.; Krühler, T.; Hjorth, J.

Long-duration gamma-ray bursts (GRBs) at z < 1 are found in most cases to be accompanied by bright, broad-lined Type Ic supernovae (SNe Ic-BL). The highest-energy GRBs are mostly located at higher redshifts, where the associated SNe are hard to detect observationally. Here, we present early and late observations of the optical counterpart of the very energetic GRB 130427A. Despite its moderate redshift, z = 0.3399 ± 0.0002, GRB 130427A is at the high end of the GRB energy distribution, with an isotropic-equivalent energy release of E{sub iso} ∼ 9.6 × 10{sup 53} erg, more than an order of magnitudemore » more energetic than other GRBs with spectroscopically confirmed SNe. In our dense photometric monitoring, we detect excess flux in the host-subtracted r-band light curve, consistent with that expected from an emerging SN, ∼0.2 mag fainter than the prototypical SN 1998bw. A spectrum obtained around the time of the SN peak (16.7 days after the GRB) reveals broad undulations typical of SNe Ic-BL, confirming the presence of an SN, designated SN 2013cq. The spectral shape and early peak time are similar to those of the high expansion velocity SN 2010bh associated with GRB 100316D. Our findings demonstrate that high-energy, long-duration GRBs, commonly detected at high redshift, can also be associated with SNe Ic-BL, pointing to a common progenitor mechanism.« less

Dust and ionized gas in active radio elliptical galaxies

NASA Technical Reports Server (NTRS)

Forbes, D. A.; Sparks, W. B.; Macchetto, F. D.

1990-01-01

The authors present broad and narrow bandwidth imaging of three southern elliptical galaxies which have flat-spectrum active radio cores (NGC 1052, IC 1459 and NGC 6958). All three contain dust and extended low excitation optical line emission, particularly extensive in the case of NGC 1052 which has a large H alpha + (NII) luminosity. Both NGC 1052 and IC 1459 have a spiral morphology in emission-line images. All three display independent strong evidence that a merger or infall event has recently occurred, i.e., extensive and infalling HI gas in NGC 1052, a counter-rotating core in IC 1459 and Malin-Carter shells in NGC 6958. This infall event is the most likely origin for the emission-line gas and dust, and the authors are currently investigating possible excitation mechanisms (Sparks et al. 1990).

Swift observations of SN2011it

NASA Astrophysics Data System (ADS)

Margutti, R.; Soderberg, A. M.; Milisavljevic, D.

2011-12-01

SN2011it has been recently classified as a broad-line type-Ic supernova (Tomasella, CBET 2938). A Swift-ToO was executed to observe the field of SN2011it starting from 2011-12-08T00:22:48 UT, with the primary aim to constrain the off-axis X-ray emission from the SN. No X-ray source is detected at the optical position of the transient with a 3 sigma upper limit of 2.4d-3 cts/s in the 0.3-10 keV energy band (total exposure= 8.3 ks).

The Broad-Lined Type Ic SN 2012ap and the Nature of Relativistic Supernovae Lacking a Gamma-Ray Burst Detection

NASA Technical Reports Server (NTRS)

Milisavljevic, D.; Margutti, R.; Parrent, J. T.; Soderberg, A. M.; Fesen, R. A.; Mazzali, P.; Maeda, K.; Sanders, N. E.; Cenko, S. B.; Silverman, J. M.

2014-01-01

We present ultraviolet, optical, and near-infrared observations of SN2012ap, a broad-lined Type Ic supernova in the galaxy NGC 1729 that produced a relativistic and rapidly decelerating outflow without a gamma-ray burst signature. Photometry and spectroscopy follow the flux evolution from -13 to +272 days past the B-band maximum of -17.4 +/- 0.5 mag. The spectra are dominated by Fe II, O I, and Ca II absorption lines at ejecta velocities of v approx. 20,000 km s(exp. -1) that change slowly over time. Other spectral absorption lines are consistent with contributions from photospheric He I, and hydrogen may also be present at higher velocities (v approx. greater than 27,000 km s(exp. -1)). We use these observations to estimate explosion properties and derive a total ejecta mass of 2.7 Solar mass, a kinetic energy of 1.0×1052 erg, and a (56)Ni mass of 0.1-0.2 Solar mass. Nebular spectra (t > 200 d) exhibit an asymmetric double-peaked [O I] lambda lambda 6300, 6364 emission profile that we associate with absorption in the supernova interior, although toroidal ejecta geometry is an alternative explanation. SN2012ap joins SN2009bb as another exceptional supernova that shows evidence for a central engine (e.g., black-hole accretion or magnetar) capable of launching a non-negligible portion of ejecta to relativistic velocities without a coincident gamma-ray burst detection. Defining attributes of their progenitor systems may be related to notable properties including above-average environmental metallicities of Z approx. greater than Solar Z, moderate to high levels of host-galaxy extinction (E(B -V ) > 0.4 mag), detection of high-velocity helium at early epochs, and a high relative flux ratio of [Ca II]/[O I] > 1 at nebular epochs. These events support the notion that jet activity at various energy scales may be present in a wide range of supernovae.

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

Taddia, Francesco; Fremling, C.; Sollerman, J.

Type Ic supernovae (SNe Ic) arise from the core-collapse of H- (and He-) poor stars, which could either be single Wolf-Rayet (WR) stars or lower-mass stars stripped of their envelope by a companion. Their light curves are radioactively powered and usually show a fast rise to peak (~10-15 d), without any early (in the first few days) emission bumps (with the exception of broad-lined SNe Ic) as sometimes seen for other types of stripped-envelope SNe (e.g., Type IIb SN 1993J and Type Ib SN 2008D). Here, we have studied iPTF15dtg, a spectroscopically normal SN Ic with an early excess inmore » the optical light curves followed by a long (~30 d) rise to the main peak. It is the first spectroscopically-normal double-peaked SN Ic to be observed. Our aim is to determine the properties of this explosion and of its progenitor star. Methods. Optical photometry and spectroscopy of iPTF15dtg was obtained with multiple telescopes. The resulting light curves and spectral sequence are analyzed and modeled with hydrodynamical and analytical models, with particular focus on the early emission. iPTF15dtg is a slow rising SN Ic, similar to SN 2011bm. Hydrodynamical modeling of the bolometric properties reveals a large ejecta mass (~10 M ⊙) and strong 56Ni mixing. The luminous early emission can be reproduced if we account for the presence of an extended (≳500 R ⊙), low-mass (≳0.045 M ⊙) envelope around the progenitor star. Alternative scenarios for the early peak, such as the interaction with a companion, a shock-breakout (SBO) cooling tail from the progenitor surface, or a magnetar-driven SBO are not favored. In conclusion, the large ejecta mass and the presence of H- and He-free extended material around the star suggest that the progenitor of iPTF15dtg was a massive (≳35 M ⊙) WR star that experienced strong mass loss.« less

iPTF15dtg: a double-peaked Type Ic supernova from a massive progenitor

DOE PAGES

Taddia, Francesco; Fremling, C.; Sollerman, J.; ...

2016-08-04

Type Ic supernovae (SNe Ic) arise from the core-collapse of H- (and He-) poor stars, which could either be single Wolf-Rayet (WR) stars or lower-mass stars stripped of their envelope by a companion. Their light curves are radioactively powered and usually show a fast rise to peak (~10-15 d), without any early (in the first few days) emission bumps (with the exception of broad-lined SNe Ic) as sometimes seen for other types of stripped-envelope SNe (e.g., Type IIb SN 1993J and Type Ib SN 2008D). Here, we have studied iPTF15dtg, a spectroscopically normal SN Ic with an early excess inmore » the optical light curves followed by a long (~30 d) rise to the main peak. It is the first spectroscopically-normal double-peaked SN Ic to be observed. Our aim is to determine the properties of this explosion and of its progenitor star. Methods. Optical photometry and spectroscopy of iPTF15dtg was obtained with multiple telescopes. The resulting light curves and spectral sequence are analyzed and modeled with hydrodynamical and analytical models, with particular focus on the early emission. iPTF15dtg is a slow rising SN Ic, similar to SN 2011bm. Hydrodynamical modeling of the bolometric properties reveals a large ejecta mass (~10 M ⊙) and strong 56Ni mixing. The luminous early emission can be reproduced if we account for the presence of an extended (≳500 R ⊙), low-mass (≳0.045 M ⊙) envelope around the progenitor star. Alternative scenarios for the early peak, such as the interaction with a companion, a shock-breakout (SBO) cooling tail from the progenitor surface, or a magnetar-driven SBO are not favored. In conclusion, the large ejecta mass and the presence of H- and He-free extended material around the star suggest that the progenitor of iPTF15dtg was a massive (≳35 M ⊙) WR star that experienced strong mass loss.« less

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

Prentice, S. J.; Mazzali, P. A.; Pian, E.

The optical and optical/near-infrared pseudo-bolometric light curves of 85 stripped-envelope supernovae (SNe) are constructed using a consistent method and a standard cosmology. The light curves are analysed to derive temporal characteristics and peak luminosity L p , enabling the construction of a luminosity function. Subsequently, the mass of 56 Ni synthesized in the explosion, along with the ratio of ejecta mass to ejecta kinetic energy, are found. Analysis shows that host-galaxy extinction is an important factor in accurately determining luminosity values as it is significantly greater than Galactic extinction in most cases. It is found that broad-lined SNe Ic (SNemore » Ic-BL) and gamma-ray burst SNe are the most luminous subtypes with a combined median L p , in erg s -1 , of log(L p) = 43.00 compared to 42.51 for SNe Ic, 42.50 for SNe Ib, and 42.36 for SNe IIb. It is also found that SNe Ic-BL synthesize approximately twice the amount of 56Ni compared with SNe Ic, Ib, and IIb, with median M Ni = 0.34, 0.16, 0.14, and 0.11 M ⊙ , respectively. SNe Ic-BL, and to a lesser extent SNe Ic, typically rise from L p /2 to L p more quickly than SNe Ib/IIb; consequently, their light curves are not as broad.« less

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

Chen, Juncheng; Wang, Xiaofeng; Li, Junzheng

We present extensive optical observations of the normal Type Ic supernova (SN) 2007gr, spanning from about one week before maximum light to more than one year thereafter. The optical light and color curves of SN 2007gr are very similar to those of the broad-lined Type Ic SN 2002ap, but the spectra show remarkable differences. The optical spectra of SN 2007gr are characterized by unusually narrow lines, prominent carbon lines, and slow evolution of the line velocity after maximum light. The earliest spectrum (taken at t = –8 days) shows a possible signature of helium (He I λ5876 at a velocitymore » of ∼19,000 km s{sup –1}). Moreover, the larger intensity ratio of the [O I] λ6300 and λ6364 lines inferred from the early nebular spectra implies a lower opacity of the ejecta shortly after the explosion. These results indicate that SN 2007gr perhaps underwent a less energetic explosion of a smaller-mass Wolf-Rayet star (∼8-9 M{sub ☉}) in a binary system, as favored by an analysis of the progenitor environment through pre-explosion and post-explosion Hubble Space Telescope images. In the nebular spectra, asymmetric double-peaked profiles can be seen in the [O I] λ6300 and Mg I] λ4571 lines. We suggest that the two peaks are contributed by the blueshifted and rest-frame components. The similarity in velocity structure and the different evolution of the strength of the two components favor an aspherical explosion with the ejecta distributed in a torus or disk-like geometry, but inside the ejecta the O and Mg have different distributions.« less

The Host Galaxies of Fast-Ejecta Core-Collapse Supernovae

NASA Technical Reports Server (NTRS)

Kelly, Patrick L.; Filippenko, Alexei V.; Modjaz, Maryam; Kocevski, Daniel

2014-01-01

Spectra of broad-lined Type Ic supernovae (SN Ic-BL), the only kind of SN observed at the locations of long-duration gamma-ray bursts (LGRBs), exhibit wide features indicative of high ejecta velocities ((is) approximately 0.1c). We study the host galaxies of a sample of 245 low-redshift (z (is) less than 0.2) core-collapse SN, including 17 SN Ic-BL, discovered by galaxy-untargeted searches, and 15 optically luminous and dust-obscured z (is) less than 1.2 LGRBs. We show that, in comparison with SDSS galaxies having similar stellar masses, the hosts of low-redshift SN Ic- BL and z (is) is less than 1.2 LGRBs have high stellar-mass and star-formation-rate densities. Core-collapse SN having typical ejecta velocities, in contrast, show no preference for such galaxies. Moreover, we find that the hosts of SN Ic-BL, unlike those of SN Ib/Ic and SN II, exhibit high gas velocity dispersions for their stellar masses. The patterns likely reflect variations among star-forming environments, and suggest that LGRBs can be used as probes of conditions in high-redshift galaxies. They may be caused by efficient formation of massive binary progenitors systems in densely star-forming regions, or, less probably, a higher fraction of stars created with the initial masses required for a SN Ic-BL or LGRB. Finally, we show that the preference of SN Ic-BL and LGRBs for galaxies with high stellar-mass and star-formation-rate densities cannot be attributed to a preference for low metal abundances but must reflect the influence of a separate environmental factor.

The bolometric light curves and physical parameters of stripped-envelope supernovae

DOE PAGES

Prentice, S. J.; Mazzali, P. A.; Pian, E.; ...

2016-02-08

The optical and optical/near-infrared pseudo-bolometric light curves of 85 stripped-envelope supernovae (SNe) are constructed using a consistent method and a standard cosmology. The light curves are analysed to derive temporal characteristics and peak luminosity L p , enabling the construction of a luminosity function. Subsequently, the mass of 56 Ni synthesized in the explosion, along with the ratio of ejecta mass to ejecta kinetic energy, are found. Analysis shows that host-galaxy extinction is an important factor in accurately determining luminosity values as it is significantly greater than Galactic extinction in most cases. It is found that broad-lined SNe Ic (SNemore » Ic-BL) and gamma-ray burst SNe are the most luminous subtypes with a combined median L p , in erg s -1 , of log(L p) = 43.00 compared to 42.51 for SNe Ic, 42.50 for SNe Ib, and 42.36 for SNe IIb. It is also found that SNe Ic-BL synthesize approximately twice the amount of 56Ni compared with SNe Ic, Ib, and IIb, with median M Ni = 0.34, 0.16, 0.14, and 0.11 M ⊙ , respectively. SNe Ic-BL, and to a lesser extent SNe Ic, typically rise from L p /2 to L p more quickly than SNe Ib/IIb; consequently, their light curves are not as broad.« less

Cytotoxic constituents of propolis from Myanmar and their structure-activity relationship.

PubMed

Li, Feng; Awale, Suresh; Tezuka, Yasuhiro; Kadota, Shigetoshi

2009-12-01

Thirteen cycloartane-type tritepenes (1-13) and four prenylated flavanones (14-17) isolated from propolis collected in Myanmar, were evaluated for their cytotoxic activity against a panel of six different cancer cell lines; three murine cancer cell lines (colon 26-L5 carcinoma, B16-BL6 melanoma, and Lewis lung carcinoma) and three human cancer cell lines (lung A549 adenocarcinoma, cervix HeLa adenocarcinoma and HT-1080 fibrosarcoma). Among them, a cycloartane-type triterpene, 3alpha,27-dihydroxycycloart-24E-en-26-oic acid (3), showed the most potent cytotoxicity against B16-BL6 cells with an IC(50) value of 5.91 microM, comparable to those of positive controls, doxorubicin (IC(50), 5.66 microM) and 5-fluorouracil (IC(50), 4.88 microM). In addition, (2S)-5,7-dihydroxy-4'-methoxy-8,3'-diprenylflavanone (14) exhibited strong cytotoxicity against all the tested cancer cell lines with the IC(50) values ranging from 14.0 to 26.4 microM. Based on the observed results, the structure-activity relationships are discussed.

SN 1994I in M51 and the nature of type Ibc supernovae

NASA Technical Reports Server (NTRS)

Wheeler, J. C.; Harkness, R. P.; Clocchiatti, A.; Benetti, S.; Brotherton, M. S.; Depoy, D. L.; Elias, J.

1994-01-01

Early spectra of SN 1994I in M51 (NGC 5194) are presented along with arguments that is a member of the class of helium-poor Type Ic supernovae. The issue of H and He in the spectra of Type Ib and Ic events is reexamined with the conclusion that Type Ib eject substantially less H than even transition events like SN 1993J and that Type Ic eject substantially less He than Type Ib and their optical spectra are consistent with no H or He. Type Ic show and absorption of the Si II lambda 6355 blend that characterizes Type Ia. This feature requires only a solar abundance of Si. Some Type Ic show an absorption that is probably C II lambda 6580. IR spectra are presented of SN 1990W which show the line of He I lambda 10830. The strength of this feature and the rather slow decay of the late time light curve suggest that this event could be better classified as a Type Ib. Even if trace abundances of H are present in Type Ib and of He in Type Ic the spectral differences still imply a distinctly different evolution for the progenitors of Type Ib from Type Ic and events like SN 1993J.

Antileukemic Activity of Tillandsia recurvata and Some of its Cycloartanes

PubMed Central

LOWE, HENRY I.C.; TOYANG, NGEH J.; WATSON, CHARAH T.; AYEAH, KENNETH N.N.; BRYANT, JOSEPH

2015-01-01

Background Approximately 250,000 deaths were caused by leukemia globally in 2012 and about 40%-50% of all leukemia diagnoses end-up in death. Medicinal plants are a rich source for the discovery of new drugs against leukemia and other types of cancers. To this end, we subjected the Jamaican ball moss (Tillandsia recurvata) and its cycloartanes, as well as some analogs, to in vitro screening against a number of leukemia cell lines. The WST-1 anti-proliferation assay was used to determine the anticancer activity of ball moss and two cycloartanes isolated from ball moss and four of their analogs against four leukemia cell lines (HL-60, K562, MOLM-14, monoMac6). Ball moss crude methanolic extract showed activity with a 50% inhibition concentration (IC50) value of 3.028 μg/ml against the Molm-14 cell line but was ineffective against HL-60 cells. The six cycloartanes tested demonstrated varying activity against the four leukemia cancer cell lines with IC50 values ranging from 1.83 μM to 18.3 μM. Five out of the six cycloartanes demonstrated activity, while one was inactive against all four cell lines. The preliminary activity demonstrated by the Jamaican ball moss and its cycloartanes against selected leukemia cell lines continues to throw light on the broad anticancer activity of ball moss. Further studies to evaluate the efficacy of these molecules in other leukemia cell lines are required in order to validate the activity of these molecules, as well as to determine their mechanisms of action and ascertain the activity in vivo in order to establish efficacy and safety profiles. PMID:24982361

Antileukemic activity of Tillandsia recurvata and some of its cycloartanes.

PubMed

Lowe, Henry I C; Toyang, Ngeh J; Watson, Charah T; Ayeah, Kenneth N N; Bryant, Joseph

2014-07-01

Approximately 250,000 deaths were caused by leukemia globally in 2012 and about 40%-50% of all leukemia diagnoses end-up in death. Medicinal plants are a rich source for the discovery of new drugs against leukemia and other types of cancers. To this end, we subjected the Jamaican ball moss (Tillandsia recurvata) and its cycloartanes, as well as some analogs, to in vitro screening against a number of leukemia cell lines. The WST-1 anti-proliferation assay was used to determine the anticancer activity of ball moss and two cycloartanes isolated from ball moss and four of their analogs against four leukemia cell lines (HL-60, K562, MOLM-14, monoMac6). Ball moss crude methanolic extract showed activity with a 50% inhibition concentration (IC50) value of 3.028 μg/ml against the Molm-14 cell line but was ineffective against HL-60 cells. The six cycloartanes tested demonstrated varying activity against the four leukemia cancer cell lines with IC50 values ranging from 1.83 μM to 18.3 μM. Five out of the six cycloartanes demonstrated activity, while one was inactive against all four cell lines. The preliminary activity demonstrated by the Jamaican ball moss and its cycloartanes against selected leukemia cell lines continues to throw light on the broad anticancer activity of ball moss. Further studies to evaluate the efficacy of these molecules in other leukemia cell lines are required in order to validate the activity of these molecules, as well as to determine their mechanisms of action and ascertain the activity in vivo in order to establish efficacy and safety profiles. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

No supernovae detected in two long-duration gamma-ray bursts.

PubMed

Watson, D; Fynbo, J P U; Thöne, C C; Sollerman, J

2007-05-15

There is strong evidence that long-duration gamma-ray bursts (GRBs) are produced during the collapse of a massive star. In the standard version of the collapsar model, a broad-lined and luminous Type Ic core-collapse supernova (SN) accompanies the GRB. This association has been confirmed in observations of several nearby GRBs. Recent observations show that some long-duration GRBs are different. No SN emission accompanied the long-duration GRBs 060505 and 060614 down to limits fainter than any known Type Ic SN and hundreds of times fainter than the archetypal SN 1998bw that accompanied GRB 980425. Multi-band observations of the early afterglows, as well as spectroscopy of the host galaxies, exclude the possibility of significant dust obscuration. Furthermore, the bursts originated in star-forming galaxies, and in the case of GRB 060505, the burst was localized to a compact star-forming knot in a spiral arm of its host galaxy. We find that the properties of the host galaxies, the long duration of the bursts and, in the case of GRB 060505, the location of the burst within its host, all imply a massive stellar origin. The absence of an SN to such deep limits therefore suggests a new phenomenological type of massive stellar death.

Magnetar-powered Supernovae in Two Dimensions. II. Broad-line Supernovae Ic

NASA Astrophysics Data System (ADS)

Chen, Ke-Jung; Moriya, Takashi J.; Woosley, Stan; Sukhbold, Tuguldur; Whalen, Daniel J.; Suwa, Yudai; Bromm, Volker

2017-04-01

Nascent neutron stars (NSs) with millisecond periods and magnetic fields in excess of 1016 Gauss can drive highly energetic and asymmetric explosions known as magnetar-powered supernovae. These exotic explosions are one theoretical interpretation for supernovae Ic-BL, which are sometimes associated with long gamma-ray bursts. Twisted magnetic field lines extract the rotational energy of the NS and release it as a disk wind or a jet with energies greater than 1052 erg over ˜20 s. What fraction of the energy of the central engine go into the wind and the jet remain unclear. We have performed two-dimensional hydrodynamical simulations of magnetar-powered supernovae (SNe) driven by disk winds and jets with the CASTRO code to investigate the effect of the central engine on nucleosynthetic yields, mixing, and light curves. We find that these explosions synthesize less than 0.05 {M}⊙ of {}56{Ni} and that this mass is not very sensitive to central engine type. The morphology of the explosion can provide a powerful diagnostic of the properties of the central engine. In the absence of a circumstellar medium, these events are not very luminous, with peak bolometric magnitudes of {M}b˜ -16.5 due to low {}56{Ni} production.

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

Inserra, C.; Smartt, S. J.; Jerkstrand, A.

We report extensive observational data for five of the lowest redshift Super-Luminous Type Ic Supernovae (SL-SNe Ic) discovered to date, namely, PTF10hgi, SN2011ke, PTF11rks, SN2011kf, and SN2012il. Photometric imaging of the transients at +50 to +230 days after peak combined with host galaxy subtraction reveals a luminous tail phase for four of these SL-SNe. A high-resolution, optical, and near-infrared spectrum from xshooter provides detection of a broad He I {lambda}10830 emission line in the spectrum (+50 days) of SN2012il, revealing that at least some SL-SNe Ic are not completely helium-free. At first sight, the tail luminosity decline rates that wemore » measure are consistent with the radioactive decay of {sup 56}Co, and would require 1-4 M{sub Sun} of {sup 56}Ni to produce the luminosity. These {sup 56}Ni masses cannot be made consistent with the short diffusion times at peak, and indeed are insufficient to power the peak luminosity. We instead favor energy deposition by newborn magnetars as the power source for these objects. A semi-analytical diffusion model with energy input from the spin-down of a magnetar reproduces the extensive light curve data well. The model predictions of ejecta velocities and temperatures which are required are in reasonable agreement with those determined from our observations. We derive magnetar energies of 0.4 {approx}< E(10{sup 51} erg) {approx}< 6.9 and ejecta masses of 2.3 {approx}< M{sub ej}(M{sub Sun }) {approx}< 8.6. The sample of five SL-SNe Ic presented here, combined with SN 2010gx-the best sampled SL-SNe Ic so far-points toward an explosion driven by a magnetar as a viable explanation for all SL-SNe Ic.« less

Simultaneous X-ray and optical observations of true type 2 Seyfert galaxies

NASA Astrophysics Data System (ADS)

Bianchi, Stefano; Panessa, Francesca; Barcons, Xavier; Carrera, Francisco J.; La Franca, Fabio; Matt, Giorgio; Onori, Francesca; Wolter, Anna; Corral, Amalia; Monaco, Lorenzo; Ruiz, Ángel; Brightman, Murray

2012-11-01

We present the results of a campaign of simultaneous X-ray and optical observations of 'true' type 2 Seyfert galaxies candidates, i.e. active galactic nuclei without a broad-line region (BLR). Out of the initial sample composed of eight sources, one object, IC 1631, was found to be a misclassified starburst galaxy, another, Q2130-431, does show broad optical lines, while other two, IRAS 01428-0404 and NGC 4698, are very likely absorbed by Compton-thick gas along the line of sight. Therefore, these four sources are not unabsorbed Seyfert 2s as previously suggested in the literature. On the other hand, we confirm that NGC 3147, NGC 3660 and Q2131-427 belong to the class of true type 2 Seyfert galaxies, since they do not show any evidence for a broad component of the optical lines nor for obscuration in their X-ray spectra. These three sources have low accretion rates (ṁ=L bol /L Edd ≲0.01), in agreement with theoretical models which predict that the BLR disappears below a critical value of Lbol/LEdd. The last source, Mrk 273x, would represent an exception even of these accretion-dependent versions of the Unification Models, due to its high X-ray luminosity and accretion rate, and no evidence for obscuration. However, its optical classification as a Seyfert 2 is only based on the absence of a broad component of Hβ, due to the lack of optical spectra encompassing the Hα band. Based on observations obtained with XMM-Newton, an ESA science mission with instruments and contributions directly funded by ESA Member States and the USA (NASA); with the TNG and Nordic Optical Telescope (NOT) operated on the island of La Palma by the Centro Galileo Galilei and the Nordic Optical Telescope Science Association, respectively, in the Spanish Observatorio del Roque de los Muchachos; at the Centro Astronómico Hispano Alemán (CAHA) at Calar Alto, operated jointly by the Max-Planck-Institut für Astronomie and the Instituto de Astrofísica de Andalucía (CSIC); at the European Organisation for Astronomical Research in the Southern hemisphere, Chile: 278.B-5021(A), 278.B-5016(A); at the Observatorio de Sierra Nevada (OSN) operated by the Instituto de Astrofísica de Andalucía (CSIC).

Abell 48 - a rare WN-type central star of a planetary nebula

NASA Astrophysics Data System (ADS)

Todt, H.; Kniazev, A. Y.; Gvaramadze, V. V.; Hamann, W.-R.; Buckley, D.; Crause, L.; Crawford, S. M.; Gulbis, A. A. S.; Hettlage, C.; Hooper, E.; Husser, T.-O.; Kotze, P.; Loaring, N.; Nordsieck, K. H.; O'Donoghue, D.; Pickering, T.; Potter, S.; Romero-Colmenero, E.; Vaisanen, P.; Williams, T.; Wolf, M.

2013-04-01

A considerable fraction of the central stars of planetary nebulae (CSPNe) are hydrogen-deficient. Almost all of these H-deficient central stars (CSs) display spectra with strong carbon and helium lines. Most of them exhibit emission-line spectra resembling those of massive WC stars. Therefore these stars are classed as CSPNe of spectral type [WC]. Recently, quantitative spectral analysis of two emission-line CSs, PB 8 and IC 4663, revealed that these stars do not belong to the [WC] class. Instead PB 8 has been classified as [WN/WC] type and IC 4663 as [WN] type. In this work we report the spectroscopic identification of another rare [WN] star, the CS of Abell 48. We performed a spectral analysis of Abell 48 with the Potsdam Wolf-Rayet (PoWR) models for expanding atmospheres. We find that the expanding atmosphere of Abell 48 is mainly composed of helium (85 per cent by mass), hydrogen (10 per cent) and nitrogen (5 per cent). The residual hydrogen and the enhanced nitrogen abundance make this object different from the other [WN] star IC 4663. We discuss the possible origin of this atmospheric composition.

Broad Halpha Wing Formation in the Planetary Nebula IC 4997.

PubMed

Lee; Hyung

2000-02-10

The young and compact planetary nebula IC 4997 is known to exhibit very broad wings with a width exceeding 5000 km s-1 around Halpha. We propose that the broad wings are formed through Rayleigh-Raman scattering that involves atomic hydrogen, by which Lybeta photons with a velocity width of a few 102 km s-1 are converted to optical photons and fill the Halpha broad wing region. The conversion efficiency reaches 0.6 near the line center, where the scattering optical depth is much larger than 1, and rapidly decreases in the far wings. Assuming that close to the central star there exists an unresolved inner compact core of high density, nH approximately 109-1010 cm-3, we use the photoionization code "CLOUDY" to show that sufficient Lybeta photons for scattering are produced. Using a top-hat-incident profile for the Lybeta flux and a scattering region with a H i column density NHi=2x1020 cm-2 and a substantial covering factor, we perform a profile-fitting analysis in order to obtain a satisfactory fit to the observed flux. We briefly discuss the astrophysical implications of the Rayleigh-Raman processes in planetary nebulae and other emission objects.

X-RAYS FROM A RADIO-LOUD COMPACT BROAD ABSORPTION LINE QUASAR 1045+352 AND THE NATURE OF OUTFLOWS IN RADIO-LOUD BROAD ABSORPTION LINE QUASARS

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

Kunert-Bajraszewska, Magdalena; Katarzynski, Krzysztof; Siemiginowska, Aneta

2009-11-10

We present new results on X-ray properties of radio-loud broad absorption line (BAL) quasars and focus on broadband spectral properties of a high-ionization BAL (HiBAL) compact steep spectrum (CSS) radio-loud quasar 1045+352. This HiBAL quasar has a very complex radio morphology indicating either strong interactions between a radio jet and the surrounding interstellar medium or a possible re-start of the jet activity. We detected 1045+352 quasar in a short 5 ksec Chandra ACIS-S observation. We applied theoretical models to explain spectral energy distribution of 1045+352 and argue that non-thermal, inverse-Compton (IC) emission from the innermost parts of the radio jetmore » can account for a large fraction of the observed X-ray emission. In our analysis, we also consider a scenario in which the observed X-ray emission from radio-loud BAL quasars can be a sum of IC jet X-ray emission and optically thin corona X-ray emission. We compiled a sample of radio-loud BAL quasars that were observed in X-rays to date and report no correlation between their X-ray and radio luminosity. However, the radio-loud BAL quasars show a large range of X-ray luminosities and absorption columns. This is consistent with the results obtained earlier for radio-quiet BAL quasars and may indicate an orientation effect in BAL quasars or more complex dependence between X-ray emission, radio emission, and an orientation based on the radio morphology.« less

Type-I interband cascade lasers near 3.2 μm

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

Jiang, Yuchao; Li, Lu; Yang, Rui Q., E-mail: Rui.Q.Yang@ou.edu

2015-01-26

Interband cascade (IC) lasers have been demonstrated based on type-I InGaAsSb/AlAsSb quantum well (QW) active regions. These type-I IC lasers are composed of 6-cascade stages and InAs/AlSb superlattice cladding layers. In contrast to the use of quinary AlGaInAsSb barriers for active region in previous type-I QW lasers, the type-I QW active region in each stage is sandwiched by digitally graded multiple InAs/AlSb QW electron injector and GaSb/AlSb QW hole injector. The fabricated type-I IC lasers were able to operate in continuous wave and pulsed modes at temperatures up to 306 and 365 K, respectively. The threshold current densities of broad-area lasersmore » were around 300 A/cm{sup 2} at 300 K with a lasing wavelength near 3.2 μm. The implications and prospects of these initial results are discussed.« less

An asymmetric energetic type Ic supernova viewed off-axis, and a link to gamma ray bursts.

PubMed

Mazzali, Paolo A; Kawabata, Koji S; Maeda, Keiichi; Nomoto, Ken'ichi; Filippenko, Alexei V; Ramirez-Ruiz, Enrico; Benetti, Stefano; Pian, Elena; Deng, Jinsong; Tominaga, Nozomu; Ohyama, Youichi; Iye, Masanori; Foley, Ryan J; Matheson, Thomas; Wang, Lifan; Gal-Yam, Avishay

2005-05-27

Type Ic supernovae, the explosions after the core collapse of massive stars that have previously lost their hydrogen and helium envelopes, are particularly interesting because of their link with long-duration gamma ray bursts. Although indications exist that these explosions are aspherical, direct evidence has been missing. Late-time observations of supernova SN 2003jd, a luminous type Ic supernova, provide such evidence. Recent Subaru and Keck spectra reveal double-peaked profiles in the nebular lines of neutral oxygen and magnesium. These profiles are different from those of known type Ic supernovae, with or without a gamma ray burst, and they can be understood if SN 2003jd was an aspherical axisymmetric explosion viewed from near the equatorial plane. If SN 2003jd was associated with a gamma ray burst, we missed the burst because it was pointing away from us.

IC 751: A New Changing Look AGN Discovered by NuSTAR

NASA Technical Reports Server (NTRS)

Ricci, C.; Bauer, F. E.; Arevalo, P.; Boggs, S.; Brandt, W. N.; Christensen, F. E.; Craig, W. W.; Ghandi, P.; Hailey, C. J.; Harrison, F. A.;

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

Kobayashi, Hirokazu

One-dimensional (1D) molecular chains of 4-substituted-2,2,6,6-tetramethyl-1-piperidinyloxyl (4-X-TEMPO) radicals were constructed in the crystalline 1D nanochannels of 2,4,6-tris(4-chlorophenoxy)-1,3,5-triazine (CLPOT) used as a template. The ESR spectra of CLPOT inclusion compounds (ICs) using 4-X-TEMPO were examined on the basis of spectral simulation using EasySpin program package for simulating and fitting ESR spectra. The ESR spectra of [(CLPOT){sub 2}-(TEMPO){sub 1.0}] IC were isotropic in the total range of temperatures. The peak-to-peak line width (ΔB{sub pp}) became monotonically narrower from 2.8 to 1.3 mT with increase in temperature in the range of 4.2–298 K. The effect of the rotational diffusion motion of TEMPO radicals inmore » the CLPOT nanochannels for the inter-spin interaction of the [(CLPOT){sub 2}-(TEMPO){sub 1.0}] IC was found to be smaller than the case of [(TPP){sub 2}−(TEMPO){sub 1.0}] IC (TPP = tris(o-phenylenedioxy)cyclotriphosphazene) reported in our previous study. The ΔB{sub pp} of the [(CLPOT){sub 2}-(TEMPO){sub 1.0}] IC in the whole range of temperatures was much narrower than the estimation to be based on the Van Vleck’s formula for the second moment of the rigid lattice model where the electron spin can be considered as fixed; 11 mT of Gaussian line-width component. This suggests the possibility of exchange narrowing in the 1D organic-radical chains of the [(CLPOT){sub 2}-(TEMPO){sub 1.0}] IC. On the other hand, the ESR spectra of [(CLPOT){sub 2}-(MeO-TEMPO){sub 0.41}] IC (MeO-TEMPO = 4-methoxy-TEMPO) were reproduced by a superposition of major broad isotropic adsorption line and minor temperature-dependent modulated triplet component. This suggests that the IC has the part of 1D organic-radical chains and MeO-TEMPO molecules isolated in the CLPOT nanochannels.« less

Surprisingly high-pressure shocks in the supernova remnant IC 443

NASA Technical Reports Server (NTRS)

Moorhouse, A.; Brand, P. W. J. L.; Geballe, T. R.; Burton, M. G.

1991-01-01

The intensities of several lines of molecular hydrogen have been measured from two regions of the supernova-remnant/molecular-cloud shock in IC 443. The lines measured have upper-state energies ranging from 7000 K to 23,000 K. Their relative intensities differ in the two regions, but are consistent with those predicted from the post-shock regions of simple jump-type shocks of different pressure. The pressures so derived are far higher than the pressure in the supernova remnant itself, and a possible reason for this discrepancy is discussed.

The effect of automobile exhaust particulates on cell viability, plating efficiency and cell division of mammalian tissue culture cells.

PubMed

Seemayer, N H; Hadnagy, W; Tomingas, R

1987-03-01

Extract of particulate matter (EPM) of gasoline engine exhaust induced only a slight loss of cell viability of mouse macrophages (line IC-21) in vitro, while a strong dose-dependent reduction of plating efficiency of human cell line A-549 and of Syrian hamster line 14-1b occurred. Cytological investigations of exposed macrophages of line IC-21 revealed an increase in the mitotic index from 1.5% of control values up to 14.6% at the highest tested concentration of EPM. Mitotic arrest is based almost exclusively on C-type mitoses occurring dose-dependently in the presence of EPM. Results indicate disturbances of the spindle apparatus in the presence of EPM.

LOSS Revisited. II. The Relative Rates of Different Types of Supernovae Vary between Low- and High-mass Galaxies

NASA Astrophysics Data System (ADS)

Graur, Or; Bianco, Federica B.; Modjaz, Maryam; Shivvers, Isaac; Filippenko, Alexei V.; Li, Weidong; Smith, Nathan

2017-03-01

In Paper I of this series, we showed that the ratio between stripped-envelope (SE) supernova (SN) and Type II SN rates reveals a significant SE SN deficiency in galaxies with stellar masses ≲ {10}10 {M}⊙ . Here, we test this result by splitting the volume-limited subsample of the Lick Observatory Supernova Search (LOSS) SN sample into low- and high-mass galaxies and comparing the relative rates of various SN types found in them. The LOSS volume-limited sample contains 180 SNe and SN impostors and is complete for SNe Ia out to 80 Mpc and core-collapse SNe out to 60 Mpc. All of these transients were recently reclassified by us in Shivvers et al. We find that the relative rates of some types of SNe differ between low- and high-mass galaxies: SNe Ib and Ic are underrepresented by a factor of ˜3 in low-mass galaxies. These galaxies also contain the only examples of SN 1987A-like SNe in the sample and host about nine times as many SN impostors. Normal SNe Ia seem to be ˜30% more common in low-mass galaxies, making these galaxies better sources for homogeneous SN Ia cosmology samples. The relative rates of SNe IIb are consistent in both low- and high-mass galaxies. The same is true for broad-line SNe Ic, although our sample includes only two such objects. The results presented here are in tension with a similar analysis from the Palomar Transient Factory, especially as regards SNe IIb.

New CO and H alpha observations of Magellanic-type irregular galaxies

NASA Astrophysics Data System (ADS)

Dettmar, Ralf-Jurgen; Becker, Renate; Shaw, Martin

In order to study the star-forming regions in Magellanic-type irregular galaxies and their relation to molecular cloud complexes, we obtained hydrogen alpha images of several southern objects. In addition, we detected and mapped some of these objects in the J = 1-0 CO line. The weak CO emission of most irregulars made it necessary to integrate for 2-8 hours per position. We describe some preliminary results for IC 4662, DDO 70 (Sex B), and IC 5052.

A defucosylated bispecific multivalent molecule exhibits broad HIV-1 neutralizing activity and enhanced ADCC against reactivated HIV-1 latently infected cells.

PubMed

Kong, Desheng; Wang, Yan; Ji, Ping; Li, Wei; Ying, Tianlei; Huang, Jinghe; Wang, Chen; Wu, Yanling; Wang, Yanping; Chen, Weizao; Hao, Yanling; Hong, Kunxue; Shao, Yiming; Dimitrov, Dimiter S; Jiang, Shibo; Ma, Liying

2018-05-11

Current treatments cannot completely eradicate HIV-1 owing to the presence of latently infected cells which harbor transcriptionally silent HIV-1. However, defucosylated antibodies can readily kill latently infected cells after their activation to express envelope glycoprotein (Env) through antibody-dependent cellular cytotoxicity (ADCC). We herein aimed to test a defucosylated bispecific multivalent molecule consisting of domain-antibody and single-domain CD4, LSEVh-LS-F, for its HIV-1 neutralizing activity and ADCC against the reactivated latently infected cells, compared with the non-defucosylated molecule LSEVh-LS. LSEVh-LS-F's neutralizing activity against a panel of newly characterized Chinese HIV-1 clinical isolates was assessed by using TZM-bl- and PBMC-based assays. LSEVh-LS-F-mediated ADCC in the presence of NK cells against cell lines that stably express Env proteins, HIV-1-infected cells and LRA-reactivated HIV-1 latent cells, was measured using a lactate dehydrogenase (LDH) cytotoxicity assay or flow cytometry. LSEVh-LS-F and LSEVh-LS were equally effective in neutralized infection of all HIV-1 isolates tested with IC50 and IC90 values 3∼4-fold lower than those of VRC01. LSEVh-LS-F was more effective in NK-mediated killing of HIV-1 Env-expressing cell lines, HIV-1-infected cells, latency reactivation agents-reactivated ACH2 cells, and reactivated latently infected resting CD4 T cell line as well as resting CD4 T lymphocytes isolated from patients receiving highly active anti-retroviral therapy (HAART). LSEVh-LS-F exhibits broad HIV-1 neutralizing activity and enhanced ADCC against HIV-1-infected cells, reactivated latently infected cell lines and primary CD4 T cells, thus being a promising candidate therapeutic for eradicating the HIV-1 reservoir.

SN 2016coi/ASASSN-16fp: An example of residual helium in a type Ic supernova?

NASA Astrophysics Data System (ADS)

Prentice, S. J.; Ashall, C.; Mazzali, P. A.; Zhang, J.-J.; James, P. A.; Wang, X.-F.; Vinkó, J.; Percival, S.; Short, L.; Piascik, A.; Huang, F.; Mo, J.; Rui, L.-M.; Wang, J.-G.; Xiang, D.-F.; Xin, Y.-X.; Yi, W.-M.; Yu, X.-G.; Zhai, Q.; Zhang, T.-M.; Hosseinzadeh, G.; Howell, D. A.; McCully, C.; Valenti, S.; Cseh, B.; Hanyecz, O.; Kriskovics, L.; Pál, A.; Sárneczky, K.; Sódor, Á.; Szakáts, R.; Székely, P.; Varga-Verebélyi, E.; Vida, K.; Bradac, M.; Reichart, D. E.; Sand, D.; Tartaglia, L.

2018-05-01

The optical observations of Ic-4 supernova (SN) 2016coi/ASASSN-16fp, from ˜2 to ˜450 days after explosion, are presented along with analysis of its physical properties. The SN shows the broad lines associated with SNe Ic-3/4 but with a key difference. The early spectra display a strong absorption feature at ˜5400 Åwhich is not seen in other SNe Ic-3/4 at this epoch. This feature has been attributed to HeIin the literature. Spectral modelling of the SN in the early photospheric phase suggests the presence of residual He in a C/O dominated shell. However, the behaviour of the HeIlines is unusual when compared with He-rich SNe, showing relatively low velocities and weakening rather than strengthening over time. The SN is found to rise to peak ˜16 d after core-collapse reaching a bolometric luminosity of Lp ˜ 3 × 1042 erg s-1. Spectral models, including the nebular epoch, show that the SN ejected 2.5 - 4 M⊙of material, with ˜1.5 M⊙below 5000 km s-1, and with a kinetic energy of (4.5 - 7) × 1051 erg. The explosion synthesised ˜0.14 M⊙of 56Ni. There are significant uncertainties in E(B - V)host and the distance however, which will affect Lp and MNi. SN 2016coi exploded in a host similar to the Large Magellanic Cloud (LMC) and away from star-forming regions. The properties of the SN and the host-galaxy suggest that the progenitor had MZAMS of 23 - 28 M⊙and was stripped almost entirely down to its C/O core at explosion.

The peculiar type II supernova 1993J in M81: Transition to the nebular phase

NASA Technical Reports Server (NTRS)

Filippenko, Alexei V.; Matheson, Thomas; Barth, Aaron J.

1994-01-01

We present optical spectra of the bright, peculiar Type II supernova 1993J in M81 spanning the first 14 months of its existence, revealing its transition to the nebular phase. Unlike the case in normal Type II supernovae, during the first 2-10 months the H-alpha emission line gradually becomes less prominent relative to other features such as (O I) lambda lambda 6300, 6364 and (Ca II) lambda lambda 7291, 7324, as we had predicted based on early-time (tau less than or approximately equal to 2 months) spectra. The nebular spectrum resembles those of the Type Ib/Ic supernovae 1985F and 1987M, although weak H-alpha emission is easily visible even at late times in SN 1993J. At tau = 8 months a close similarity is found with the spectrum of SN 1987K, the only other Type II supernova known to have undergone such a metamorphosis. The emission lines are considerably broader than those of normal Type II supernovae at comparable phases, consistent with the progenitor having lost a majority of its hydrogen envelope prior to exploding. Consequently, there is now little doubt that Type Ib, and probably Type Ic, supernovae result from core collapse in stripped, massive stars; models of the chemical evolution of galaxies in which these subtypes are ascribed to exploding white dwarfs must be appropriately modified. Although all of the emission lines in spectra of SN 1993J fade roughly exponentially for a considerable time, the fading of H-alpha begins to slow down at tau approximately = 8 months, and in the interval tau = 10-14 months its flux is constant, or even slightly rising in the wings of the line. This behavior, together with the box-like shape and great breadth (full width at half maximum (FWHM) approximately = 17 000 km/s) of the line profile, suggests that the H-alpha emission is being produced by the high-velocity outer layer of hydrogen ejecta interacting with circumstellar gas released by the progenitor prior to its explosion. A similar phenomenon has previously been seen at later phases in several Type II supernovae, most notably SN 1980K. Bumps (FWHM approximately = 1000 km/s, amplitude approximately = 20%) in the H-alpha profile are probably indicative of Rayleigh-Taylor instabilities in the cool gas behind the reverse shock. A very narrow component (unresolved, FWHM less than or approximately equal to 200 km/s) of H-alpha at the symmetric velocity of SN 1993J may instead be produced by a superposed H II region, or perhaps by recombination in a large circumstellar shell or ring that was ionized during the first few hours after outburst. In the near future the spectrum of SN 1993J should become increasingly dominated by broad H-alpha emission.

[WN] central stars of planetary nebulae

NASA Astrophysics Data System (ADS)

Todt, H.; Miszalski, B.; Toalá, J. A.; Guerrero, M. A.

2017-10-01

While most of the low-mass stars stay hydrogen-rich on their surface throughout their evolution, a considerable fraction of white dwarfs as well as central stars of planetary nebulae have a hydrogen-deficient surface composition. The majority of these H-deficient central stars exhibit spectra very similar to massive Wolf-Rayet stars of the carbon sequence, i.e. with broad emission lines of carbon, helium, and oxygen. In analogy to the massive Wolf-Rayet stars, they are classified as [WC] stars. Their formation, which is relatively well understood, is thought to be the result of a (very) late thermal pulse of the helium burning shell. It is therefore surprising that some H-deficient central stars which have been found recently, e.g. IC 4663 and Abell 48, exhibit spectra that resemble those of the massive Wolf-Rayet stars of the nitrogen sequence, i.e. with strong emission lines of nitrogen instead of carbon. This new type of central stars is therefore labelled [WN]. We present spectral analyses of these objects and discuss the status of further candidates as well as the evolutionary status and origin of the [WN] stars.

Withaferin-A induces apoptosis in osteosarcoma U2OS cell line via generation of ROS and disruption of mitochondrial membrane potential.

PubMed

Li, A-X; Sun, M; Li, X

2017-03-01

Withaferin-A (WF-A) is a well-known dietary compound isolated from Withania somnifera. It has marked pharmacological potential and has been shown to exhibit antiproliferative activity against several types of cancerous cells. Currently, the main focus of anti-cancer therapeutic development is to identify apoptosis-inducing drug-like molecules. Osteosarcoma is a rare type of bone cancer affecting humans. The objective of the present study was therefore to evaluate the antitumor potential of WF-A against several osteosarcoma cell lines. MTT assay was used to evaluate WF-A against osteosarcoma cell lines and to calculate the IC50. DAPI staining was used to confirm the apoptosis-inducing potential of WF-A. Mitochondrial membrane potential, reactive oxygen species (ROS) assay, and Western blotting were used to confirm the basis of apoptosis. The results of the present study revealed that WF-A exhibited strong antiproliferative activity against all the cells lines, with IC50 ranging from 0.32 to 7.6 µM. The lowest IC50 (0.32 µM) was observed against U2OS cell line and, therefore, it was selected for further analysis. DAPI staining indicated that WF-A exhibited antiproliferative activity via induction of apoptosis. Moreover, WF-A induced a ROS-mediated reduction in mitochondrial membrane potential in a dose-dependent manner and activation of caspase-3 in osteosarcoma cells. We suggest that WF-A may prove a potent therapeutic agent for inducing apoptosis in osteosarcoma cell lines via generation of ROS and disruption of mitochondrial membrane potential.

Identification and isolation of the cyclooxygenase-2 inhibitory principle in Isatis tinctoria.

PubMed

Danz, H; Stoyanova, S; Wippich, P; Brattström, A; Hamburger, M

2001-07-01

Various extracts prepared from the traditional dye and medicinal plant Isatis tinctoria L. were submitted to a broad in vitro screening against 16 anti-inflammatory targets. Dichloromethane (DCM) extracts from dried leaves showed a marked cyclooxygenase (COX) inhibitory activity with a preferential effect on COX-2 catalysed prostaglandin synthesis. A supercritical fluid extraction (SFE) procedure employing CO2-modifier mixtures was developed by which the bioactivity profile and chromatographic fingerprint of the DCM extract could be reproduced. High-resolution activity directed on-line identification of the COX-2 inhibitory principle, using a combination of LC-DAD-MS with a microtitre-based bioassay, led to the identification of tryptanthrin (1) as the constituent responsible for essentially all COX-2 inhibitory activity in the crude extract. Following on-line identification, 1 was isolated at preparative scale and its structure confirmed by comparison with synthetic tryptanthrin. In an assay with lipopolysaccharide stimulated Mono Mac 6 cells, tryptanthrin (1) was of comparable potency (IC50 = 64 nM) than the preferential COX-2 inhibitors nimesulide (IC50 = 39 nM) and NS 398 (IC50 = 2 nM). The SFE extract and 1 showed no cytotoxicity in Mono Mac 6 and RAW 264.7 cells when tested at 100 microg/ml and 10 microM, respectively.

Silicon ball grid array chip carrier

DOEpatents

Palmer, David W.; Gassman, Richard A.; Chu, Dahwey

2000-01-01

A ball-grid-array integrated circuit (IC) chip carrier formed from a silicon substrate is disclosed. The silicon ball-grid-array chip carrier is of particular use with ICs having peripheral bond pads which can be reconfigured to a ball-grid-array. The use of a semiconductor substrate such as silicon for forming the ball-grid-array chip carrier allows the chip carrier to be fabricated on an IC process line with, at least in part, standard IC processes. Additionally, the silicon chip carrier can include components such as transistors, resistors, capacitors, inductors and sensors to form a "smart" chip carrier which can provide added functionality and testability to one or more ICs mounted on the chip carrier. Types of functionality that can be provided on the "smart" chip carrier include boundary-scan cells, built-in test structures, signal conditioning circuitry, power conditioning circuitry, and a reconfiguration capability. The "smart" chip carrier can also be used to form specialized or application-specific ICs (ASICs) from conventional ICs. Types of sensors that can be included on the silicon ball-grid-array chip carrier include temperature sensors, pressure sensors, stress sensors, inertia or acceleration sensors, and/or chemical sensors. These sensors can be fabricated by IC processes and can include microelectromechanical (MEM) devices.

Diagnostic and prognostic value of human prion detection in cerebrospinal fluid.

PubMed

Foutz, Aaron; Appleby, Brian S; Hamlin, Clive; Liu, Xiaoqin; Yang, Sheng; Cohen, Yvonne; Chen, Wei; Blevins, Janis; Fausett, Cameron; Wang, Han; Gambetti, Pierluigi; Zhang, Shulin; Hughson, Andrew; Tatsuoka, Curtis; Schonberger, Lawrence B; Cohen, Mark L; Caughey, Byron; Safar, Jiri G

2017-01-01

Several prion amplification systems have been proposed for detection of prions in cerebrospinal fluid (CSF), most recently, the measurements of prion seeding activity with second-generation real-time quaking-induced conversion (RT-QuIC). The objective of this study was to investigate the diagnostic performance of the RT-QuIC prion test in the broad phenotypic spectrum of prion diseases. We performed CSF RT-QuIC testing in 2,141 patients who had rapidly progressive neurological disorders, determined diagnostic sensitivity and specificity in 272 cases that were autopsied, and evaluated the impact of mutations and polymorphisms in the PRNP gene, and type 1 or type 2 human prions on diagnostic performance. The 98.5% diagnostic specificity and 92% sensitivity of CSF RT-QuIC in a blinded retrospective analysis matched the 100% specificity and 95% sensitivity of a blind prospective study. The CSF RT-QuIC differentiated 94% of cases of sporadic Creutzfeldt-Jakob disease (sCJD) MM1 from the sCJD MM2 phenotype, and 80% of sCJD VV2 from sCJD VV1. The mixed prion type 1-2 and cases heterozygous for codon 129 generated intermediate CSF RT-QuIC patterns, whereas genetic prion diseases revealed distinct profiles for each PRNP gene mutation. The diagnostic performance of the improved CSF RT-QuIC is superior to surrogate marker tests for prion diseases such as 14-3-3 and tau proteins, and together with PRNP gene sequencing the test allows the major prion subtypes to be differentiated in vivo. This differentiation facilitates prediction of the clinicopathological phenotype and duration of the disease-two important considerations for envisioned therapeutic interventions. ANN NEUROL 2017;81:79-92. © 2016 American Neurological Association.

Diagnostic and Prognostic Value of Human Prion Detection in Cerebrospinal Fluid

PubMed Central

Foutz, Aaron; Appleby, Brian S.; Hamlin, Clive; Liu, Xiaoqin; Yang, Sheng; Cohen, Yvonne; Chen, Wei; Blevins, Janis; Fausett, Cameron; Wang, Han; Gambetti, Pierluigi; Zhang, Shulin; Hughson, Andrew; Tatsuoka, Curtis; Schonberger, Lawrence B.; Cohen, Mark L.; Caughey, Byron; Safar, Jiri G.

2016-01-01

Objective Several prion amplification systems have been proposed for detection of prions in cerebrospinal fluid (CSF), most recently, the measurements of prion seeding activity with second-generation real-time quaking-induced conversion (RT-QuIC). The objective of this study was to investigate the diagnostic performance of the RT-QuIC prion test in the broad phenotypic spectrum of prion diseases. Methods We performed CSF RT-QuIC testing in 2,141 patients who had rapidly progressive neurological disorders, determined diagnostic sensitivity and specificity in 272 cases which were autopsied, and evaluated the impact of mutations and polymorphisms in the PRNP gene, and Type 1 or Type 2 of human prions on diagnostic performance. Results The 98.5% diagnostic specificity and 92% sensitivity of CSF RT-QuIC in a blinded retrospective analysis matched the 100% specificity and 95% sensitivity of a blind prospective study. The CSF RT-QuIC differentiated 94% of cases of sporadic Creutzfeldt-Jakob disease (sCJD) MM1 from the sCJD MM2 phenotype, and 80% of sCJD VV2 from sCJD VV1. The mixed prion type 1–2 and cases heterozygous for codon 129 generated intermediate CSF RT-QuIC patterns, while genetic prion diseases revealed distinct profiles for each PRNP gene mutation. Interpretation The diagnostic performance of the improved CSF RT-QuIC is superior to surrogate marker tests for prion diseases such as 14-3-3 and Tau proteins and together with PRNP gene sequencing, the test allows the major prion subtypes to be differentiated in vivo. This differentiation facilitates prediction of the clinicopathological phenotype and duration of the disease—two important considerations for envisioned therapeutic interventions. PMID:27893164

Galaxy and Mass Assembly (GAMA): active galactic nuclei in pairs of galaxies

NASA Astrophysics Data System (ADS)

Gordon, Yjan A.; Owers, Matt S.; Pimbblet, Kevin A.; Croom, Scott M.; Alpaslan, Mehmet; Baldry, Ivan K.; Brough, Sarah; Brown, Michael J. I.; Cluver, Michelle E.; Conselice, Christopher J.; Davies, Luke J. M.; Holwerda, Benne W.; Hopkins, Andrew M.; Gunawardhana, Madusha L. P.; Loveday, Jonathan; Taylor, Edward N.; Wang, Lingyu

2017-03-01

There exist conflicting observations on whether or not the environment of broad- and narrow-line active galatic nuclei (AGN) differ and this consequently questions the validity of the AGN unification model. The high spectroscopic completeness of the Galaxy and Mass Assembly (GAMA) survey makes it ideal for a comprehensive analysis of the close environment of galaxies. To exploit this, and conduct a comparative analysis of the environment of broad- and narrow-line AGN within GAMA, we use a double-Gaussian emission line fitting method to model the more complex line profiles associated with broad-line AGN. We select 209 type 1 (I.e. unobscured), 464 type 1.5-1.9 (partially obscured), and 281 type 2 (obscured) AGN within the GAMA II data base. Comparing the fractions of these with neighbouring galaxies out to a pair separation of 350 kpc h-1 and Δz < 0.012 shows no difference between AGN of different type, except at separations less than 20 kpc h-1 where our observations suggest an excess of type 2 AGN in close pairs. We analyse the properties of the galaxies neighbouring our AGN and find no significant differences in colour or the star formation activity of these galaxies. Further to this, we find that Σ5 is also consistent between broad- and narrow-line AGN. We conclude that the observations presented here are consistent with AGN unification.

Interstellar Lithium and Rubidium in the Diffuse Gas Near IC 443

NASA Astrophysics Data System (ADS)

Ritchey, Adam M.; Taylor, C. J.; Federman, S. R.; Lambert, D. L.

2011-01-01

We present an analysis of interstellar lithium and rubidium from observations made with the Hobby-Eberly Telescope at McDonald Observatory of the Li I λ6707 and Rb I λ7800 absorption lines along four lines of sight through the supernova remnant IC 443. The observations probe interstellar material polluted by the ejecta of a core-collapse (Type II) supernova and can thus be used to constrain the contribution from massive stars to the synthesis of lithium and rubidium. Production of 7Li is expected to occur through neutrino spallation in the helium and carbon shells of the progenitor star during the terminal supernova explosion, while both 6Li and 7Li are synthesized via spallation and fusion reactions involving cosmic rays accelerated by the remnant. Gamma-ray emission from IC 443 provides strong evidence for the interaction of accelerated cosmic rays with the ambient atomic and molecular gas. Rubidium is also produced by massive stars through the weak s-process in the He- and C-burning shells and the r-process during core collapse. We examine interstellar 7Li/6Li isotope ratios as well as Li/K and Rb/K ratios along each line of sight, and discuss the implications of our results in the context of nucleosynthesis associated with Type II supernovae.

Cytotoxic activity of quassinoids from Eurycoma longifolia.

PubMed

Miyake, Katsunori; Li, Feng; Tezuka, Yasuhiro; Awale, Suresh; Kadota, Shigetoshi

2010-07-01

Twenty-four quassinoids isolated from Eurycoma longifolia Jack were investigated for their cytotoxicity against a panel of four different cancer cell lines, which includes three murine cell lines [colon 26-L5 carcinoma (colon 26-L5), B16-BL6 melanoma (B16-BL6), Lewis lung carcinoma (LLC)] and a human lung A549 adenocarcinoma (A549) cell line. Among the tested compounds, eurycomalactone (9) displayed the most potent activity against all the tested cell lines; colon 26-L5 (IC50 = 0.70 microM), B16-BL6 (IC50 = 0.59 microM), LLC (IC50 = 0.78 microM), and A549 (IC50 = 0.73 microM). These activities were comparable to clinically used anticancer agent doxorubicin (colon 26-L5, IC50 = 0.76 microM; B16-BL6, IC50 = 0.86 microM; LLC, IC50 = 0.80 microM; A549, IC50 = 0.66 microM).

Umbelliprenin is cytotoxic against QU-DB large cell lung cancer cell line but anti-proliferative against A549 adenocarcinoma cells

PubMed Central

2012-01-01

Background Umbelliprenin is a natural compound, belonging to the class of sesquiterpene coumarins. Recently, umbelliprenin has attracted the researchers' attention for its antitumor activities against skin tumors. Its effect on lung cancer is largely unknown. The aim of our study was to investigate the effects of this natural compound, which is expected to have low adverse effects, on lung cancer. Methods The QU-DB large cell and A549 adenocarcinoma lung cancer cell lines were treated with umbelliprenin. IC50 values were estimated using methyl thiazolely diphenyl-tetrazolium bromide (MTT) assay, in which a decrease in MTT reduction can occur as a result of cell death or cell proliferation inhibition. To quantify the rate of cell death at IC50 values, flow cytometry using Annexin V-FITC (for apoptotic cells), and propidium iodide (for necrotic cells) dyes were employed. Results Data from three independent MTT experiments in triplicate revealed that IC50 values for QU-DB and A549 were 47 ± 5.3 μM and 52 ± 1.97 μM, respectively. Annexin V/PI staining demonstrated that umbelliprenin treatment at IC50 induced 50% cell death in QU-DB cells, but produced no significant death in A549 cells until increasing the umbelliprenin concentration to IC80. The pattern of cell death was predominantly apoptosis in both cell lines. When peripheral blood mononuclear cells were treated with 50 μM and less concentrations of umbelliprenin, no suppressive effect was observed. Conclusions We found cytotoxic/anti-proliferative effects of umbelliprenin against two different types of lung cancer cell lines. PMID:23351548

Partial Transient Liquid-Phase Bonding, Part II: A Filtering Routine for Determining All Possible Interlayer Combinations

NASA Astrophysics Data System (ADS)

Cook, Grant O.; Sorensen, Carl D.

2013-12-01

Partial transient liquid-phase (PTLP) bonding is currently an esoteric joining process with limited applications. However, it has preferable advantages compared with typical joining techniques and is the best joining technique for certain applications. Specifically, it can bond hard-to-join materials as well as dissimilar material types, and bonding is performed at comparatively low temperatures. Part of the difficulty in applying PTLP bonding is finding suitable interlayer combinations (ICs). A novel interlayer selection procedure has been developed to facilitate the identification of ICs that will create successful PTLP bonds and is explained in a companion article. An integral part of the selection procedure is a filtering routine that identifies all possible ICs for a given application. This routine utilizes a set of customizable parameters that are based on key characteristics of PTLP bonding. These parameters include important design considerations such as bonding temperature, target remelting temperature, bond solid type, and interlayer thicknesses. The output from this routine provides a detailed view of each candidate IC along with a broad view of the entire candidate set, greatly facilitating the selection of ideal ICs. This routine provides a new perspective on the PTLP bonding process. In addition, the use of this routine, by way of the accompanying selection procedure, will expand PTLP bonding as a viable joining process.

An abundance study of IC 418 using high-resolution, signal-to-noise emission spectra

NASA Astrophysics Data System (ADS)

Sharpee, Brian David

2003-11-01

An on-going problem in astrophysics involves the large and varying disagreement between abundances measurements made in planetary nebulae (PNe), determined from the strengths of emission lines arising from the same source ion, but excited by differing mechanisms (recombination and collisional excitation) in planetary nebulae (PNe). We investigate the extent of this problem in IC 418, a PN chosen for its great surface brightness and perceived visually uncomplicated geometry, through the use of high resolution (R ≈ 30000 = 10 km sec-1 at 6500Å) echelle emission spectroscopy in the optical regime (3500 9850Å). These observations allow us to construct the most detailed list of atomic emission lines ever compiled for IC 418, and among the most detailed from among all PNe. Ionic abundances are calculated from the fluxes of numerous weak (1 × 10-5 Hβ) atomic emission lines from the ions of C,N,O, and Ne, using the most recent and accurate atomic transition information presently available. The high resolution of these spectra provides well-defined line profiles, which, coupled with the perceived simplicity of the object's expansion velocity distribution, allows us to better determine where in the nebula lines are formed, and where the ions that produce them are concentrated. Evidence for “non-conventional” line excitation mechanisms, such as continuum fluorescence from the ground state or enhanced dielectronic recombination, is sought in the profile morphologies and relative line strengths. Non-conventional excitation processes may influence the strengths of lines enough to significantly alter abundances calculated from them. Our calculations show that recombination line-derived abundances exceed those derived from collisionally excited lines, for those ions for which we observed lines of both types: O+, O+2, and Ne +2 by real and varying amounts. We find that both continuum fluorescence and dielectronic recombination excites numerous lines in IC 418, but that there is no evidence in our data that either process is responsible for the observed overabundances in all recombination lines as opposed to their collisionally excited counterparts. The calculated levels of temperature fluctuations in the zones in which these ion reside are dubious, and significantly exceed model predicted values. In summary, no satisfactory, single universally applicable answer to the abundance discrepancy problem shown to exist by us in IC 418, is revealed by our observations. We developed several new techniques to analyze these data. Of particular interest is EMILI (Emission Line Identifier), a public-domain program that utilizes a comprehensive atomic transition list and a set of simple tests and criteria, to quickly provide its user with a list of rank ordered IDs for unidentified emission lines found in deep, high resolution spectra. Presented here are the results of applying EMILI to the identification of weak emission lines in the spectra of IC 418 and other PNe.

A multi-wavelength investigation of Seyfert 1.8 and 1.9 galaxies

NASA Astrophysics Data System (ADS)

Trippe, Margaret L.

We focus on determining the underlying physical cause of a Seyfert galaxy's appearance as type a 1.8 or 1.9. Are these "intermediate" Seyfert types typical Seyfert 1 nuclei reddened by central dusty tori or by nuclear dust lanes/spirals in the narrow-line region? Or, are they similar to NGC 2992, objects that have intrinsically weak continua and weak broad emission lines? Our study compares measurements of the reddenings of the narrow and broad-line regions with each other and with the X-ray column derived from XMM Newton 0.5--10 keV spectra to determine the presence and location of dust in the line of sight for a sample of 35 Seyfert 1.8s and 1.9s. From this, we find that Seyfert 1.9s are an almost equal mix of low-flux objects with unreddened broad line regions, and objects with broad line regions reddened by an internal dust source, either the torus or dust structures on the same size scale as the narrow line region. The 1.9s that recieved this designation due to a low continuum flux state showed variable type classifications. All three of the Seyfert 1.8s in our study are probably in low continuum states. Many objects have been misclassified as Seyfert 1.8/1.9s in the past, probably due to improper [N II]/Halpha deconvolution leading to a false detection of weak broad Halpha. INDEX WORDS: Active galaxies, Seyfert galaxies, Optical spectroscopy, X-ray spectroscopy, Astronomical dust

DISCOVERY OF SN 2009nz ASSOCIATED WITH GRB 091127

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

Cobb, B. E.; Bloom, J. S.; Perley, D. A.

2010-08-01

We report SMARTS, Gemini, and Swift-UVOT observations of the optical transient (OT) associated with gamma-ray burst (GRB) 091127, at redshift 0.49, taken between 0.9 hr and 102 days following the Swift trigger. In our early-time observations, the OT fades in a manner consistent with previously observed GRB afterglows. However, after nine days post-burst, the OT is observed to brighten for a period of {approx}two weeks, after which the source resumes fading. A comparison of this late-time 'bump' to SN 1998bw (the broad-lined Type Ic supernova associated with GRB 980425), and several other GRB supernovae (SNe), indicates that the most straightforwardmore » explanation is that GRB 091127 was accompanied by a contemporaneous SN (SN 2009nz) that peaked at a magnitude of M{sub V} = -19.0 {+-} 0.2. SN 2009nz is globally similar to other GRB SNe, but evolves slightly faster than SN 1998bw and reaches a slightly dimmer peak magnitude. We also analyze the early-time UV-optical-IR spectral energy distribution of the afterglow of GRB 091127 and find that there is little to no reddening in the host galaxy along the line of sight to this burst.« less

Withaferin-A Induces Apoptosis in Osteosarcoma U2OS Cell Line via Generation of ROS and Disruption of Mitochondrial Membrane Potential.

PubMed

Zhang, Hui-Liang; Zhang, Hong

2017-01-01

Withaferin-A (WF-A) is a well-known dietary compound isolated from Withania sominifera . It has tremendous pharmacological potential and has been shown to exhibit antiproliferative activity against several types of cancerous cells. Currently, the main focus of anti-cancer therapeutic development is to identify apoptosis inducing drug-like molecules. Osteosarcoma is a rare type of osteocancer, affecting human. The present study therefore focused on the evaluation of antitumor potential of WF-A against several osteosarcoma cell lines. MTT assay was used to evaluate WF-A against osteosarcoma cell lines and to calculate the IC 50 . DAPI staining was used to confirm the apoptosis inducing potential of WF-A. Mitochondrial membrane potential, reactive oxygen species (ROS) assay, and Western blotting were used to confirm the basis of apoptosis. The results revealed that that WF-A exhibited strong antiproliferative activity against all the cells lines, with IC 50 ranging from 0.32 to 7.6 μM. The lowest IC 50 (0.32 μM) was observed against U2OS cell line and therefore it was selected for further analysis. DAPI staining indicated that WF-A exhibited antiproliferative activity via induction of apoptosis. Moreover, WF-A induced ROS-mediated reduction in mitochondrial membrane potential ΔΨm) in a dose-dependent manner and activation of caspase-3 in osteosarcoma cells. We propose that WF-A may prove a potent therapeutic agent for inducing apoptosis in osteosarcoma cell lines via generation of ROS and disruption of mitochondrial membrane potential. WF-A exhibits strong anticancer activity against osteosarcoma cell linesAntiproliferative activity of WF-A is via induction of apoptosisWF-A induced ROS-mediated reduction in mitochondrial membrane potentialWF-A induced expression of caspase-3 in osteosarcoma cells. Abbreviations used: WA: Withaferin A; ROS: Reactive oxygen species; OS: Osteosarcoma; MMP: Mitochondrial membrane potential.

Optical spectra of 73 stripped-envelope core-collapse supernovae

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

Modjaz, M.; Bianco, F. B.; Liu, Y. Q.

2014-05-01

We present 645 optical spectra of 73 supernovae (SNe) of Types IIb, Ib, Ic, and broad-lined Ic. All of these types are attributed to the core collapse of massive stars, with varying degrees of intact H and He envelopes before explosion. The SNe in our sample have a mean redshift (cz) = 4200 km s{sup –1}. Most of these spectra were gathered at the Harvard-Smithsonian Center for Astrophysics (CfA) between 2004 and 2009. For 53 SNe, these are the first published spectra. The data coverage ranges from mere identification (1-3 spectra) for a few SNe to extensive series of observationsmore » (10-30 spectra) that trace the spectral evolution for others, with an average of 9 spectra per SN. For 44 SNe of the 73 SNe presented here, we have well-determined dates of maximum light to determine the phase of each spectrum. Our sample constitutes the most extensive spectral library of stripped-envelope SNe to date. We provide very early coverage (as early as 30 days before V-band max) for photospheric spectra, as well as late-time nebular coverage when the innermost regions of the SN are visible (as late as 2 yr after explosion, while for SN 1993J, we have data as late as 11.6 yr). This data set has homogeneous observations and reductions that allow us to study the spectroscopic diversity of these classes of stripped SNe and to compare these to SNe-gamma-ray bursts. We undertake these matters in follow-up papers.« less

30 CFR 57.22210 - In-line filters (I-C mines).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false In-line filters (I-C mines). 57.22210 Section... Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22210 In-line filters (I-C mines). Filters or separators shall be installed on air-lift fan systems to prevent explosive concentrations of...

30 CFR 57.22210 - In-line filters (I-C mines).

Code of Federal Regulations, 2013 CFR

2013-07-01

... 30 Mineral Resources 1 2013-07-01 2013-07-01 false In-line filters (I-C mines). 57.22210 Section... Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22210 In-line filters (I-C mines). Filters or separators shall be installed on air-lift fan systems to prevent explosive concentrations of...

30 CFR 57.22210 - In-line filters (I-C mines).

Code of Federal Regulations, 2012 CFR

2012-07-01

... 30 Mineral Resources 1 2012-07-01 2012-07-01 false In-line filters (I-C mines). 57.22210 Section... Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22210 In-line filters (I-C mines). Filters or separators shall be installed on air-lift fan systems to prevent explosive concentrations of...

30 CFR 57.22210 - In-line filters (I-C mines).

Code of Federal Regulations, 2014 CFR

2014-07-01

... 30 Mineral Resources 1 2014-07-01 2014-07-01 false In-line filters (I-C mines). 57.22210 Section... Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22210 In-line filters (I-C mines). Filters or separators shall be installed on air-lift fan systems to prevent explosive concentrations of...

30 CFR 57.22210 - In-line filters (I-C mines).

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false In-line filters (I-C mines). 57.22210 Section... Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22210 In-line filters (I-C mines). Filters or separators shall be installed on air-lift fan systems to prevent explosive concentrations of...

Antitumor Activity and Induction of TP53-Dependent Apoptosis toward Ovarian Clear Cell Adenocarcinoma by the Dual PI3K/mTOR Inhibitor DS-7423

PubMed Central

Kashiyama, Tomoko; Oda, Katsutoshi; Ikeda, Yuji; Shiose, Yoshinobu; Hirota, Yasuhide; Inaba, Kanako; Makii, Chinami; Kurikawa, Reiko; Miyasaka, Aki; Koso, Takahiro; Fukuda, Tomohiko; Tanikawa, Michihiro; Shoji, Keiko; Sone, Kenbun; Arimoto, Takahide; Wada-Hiraike, Osamu; Kawana, Kei; Nakagawa, Shunsuke; Matsuda, Koichi; McCormick, Frank; Aburatani, Hiroyuki; Yano, Tetsu; Osuga, Yutaka; Fujii, Tomoyuki

2014-01-01

DS-7423, a novel, small-molecule dual inhibitor of phosphatidylinositol-3-kinase (PI3K) and mammalian target of rapamycin (mTOR), is currently in phase I clinical trials for solid tumors. Although DS-7423 potently inhibits PI3Kα (IC50 = 15.6 nM) and mTOR (IC50 = 34.9 nM), it also inhibits other isoforms of class I PI3K (IC50 values: PI3Kβ = 1,143 nM; PI3Kγ = 249 nM; PI3Kδ = 262 nM). The PI3K/mTOR pathway is frequently activated in ovarian clear cell adenocarcinomas (OCCA) through various mutations that activate PI3K-AKT signaling. Here, we describe the anti-tumor effect of DS-7423 on a panel of nine OCCA cell lines. IC50 values for DS-7423 were <75 nM in all the lines, regardless of the mutational status of PIK3CA. In mouse xenograft models, DS-7423 suppressed the tumor growth of OCCA in a dose-dependent manner. Flow cytometry analysis revealed a decrease in S-phase cell populations in all the cell lines and an increase in sub-G1 cell populations following treatment with DS-7423 in six of the nine OCCA cell lines tested. DS-7423-mediated apoptosis was induced more effectively in the six cell lines without TP53 mutations than in the three cell lines with TP53 mutations. Concomitantly with the decreased phosphorylation level of MDM2 (mouse double minute 2 homolog), the level of phosphorylation of TP53 at Ser46 was increased by DS-7423 in the six cell lines with wild-type TP53, with induction of genes that mediate TP53-dependent apoptosis, including p53AIP1 and PUMA at 39 nM or higher doses. Our data suggest that the dual PI3K/mTOR inhibitor DS-7423 may constitute a promising molecular targeted therapy for OCCA, and that its antitumor effect might be partly obtained by induction of TP53-dependent apoptosis in TP53 wild-type OCCAs. PMID:24504419

Amantelides A and B, Polyhydroxylated Macrolides with Differential Broad Spectrum Cytotoxicity from a Guamanian Marine Cyanobacterium

PubMed Central

Salvador-Reyes, Lilibeth A.; Sneed, Jennifer; Paul, Valerie J.; Luesch, Hendrik

2016-01-01

Cytotoxicity-guided fractionation of a Guamanian cyanobacterial collection yielded the new compounds amantelides A (1) and B (2). These polyketides are characterized by a 40-membered macrolactone ring consisting of a 1,3-diol and contiguous 1,5-diol units and a tert-butyl substituent. Amantelide A (1) displayed potent cytotoxicity with sub-micromolar IC50 against HT29 colorectal adenocarcinoma and HeLa cervical carcinoma cell lines. Acetylation of the hydroxy group at C-33 in 2 caused a close to 10-fold decrease in potency. Exhaustive acetylation of the hydroxy groups abrogated the antiproliferative activity of amantelide A (1) by 20–67-fold. Further bioactivity assessment of 1 against bacterial pathogens and marine fungi indicated a broad spectrum of bioactivity. PMID:26204500

Chemical composition and cytotoxicity evaluation of essential oil from leaves of Casearia sylvestris, its main compound α-zingiberene and derivatives.

PubMed

Bou, Diego Dinis; Lago, João Henrique G; Figueiredo, Carlos R; Matsuo, Alisson L; Guadagnin, Rafael C; Soares, Marisi G; Sartorelli, Patricia

2013-08-08

Casearia sylvestris (Salicaceae), popularly known as "guaçatonga", is a plant widely used in folk medicine to treat various diseases, including cancer. The present work deals with the chemical composition as well as the cytotoxic evaluation of its essential oil, its main constituent and derivatives. Thus, the crude essential oil from leaves of C. sylvestris was obtained using a Clevenger type apparatus and analyzed by GC/MS. This analysis afforded the identification of 23 substances, 13 of which corresponded to 98.73% of the total oil composition, with sesquiterpene a-zingiberene accounting for 50% of the oil. The essential oil was evaluated for cytotoxic activity against several tumor cell lines, giving IC50 values ranging from 12 to 153 mg/mL. Pure a-zingiberene, isolated from essential oil, was also evaluated against the tumor cell lines showing activity for HeLa, U-87, Siha and HL60 cell lines, but with IC50 values higher than those determined for the crude essential oil. Aiming to evaluate the effect of the double bonds of a-zingiberene on the cytotoxic activity, partially hydrogenated a-zingiberene (PHZ) and fully hydrogenated a-zingiberene (THZ) derivatives were obtained. For the partially hydrogenated derivative only cytotoxic activity to the B16F10-Nex2 cell line (IC50 65 mg/mL) was detected, while totally hydrogenated derivative showed cytotoxic activity for almost all cell lines, with B16F10-Nex2 and MCF-7 as exceptions and with IC50 values ranging from 34 to 65 mg/mL. These results indicate that cytotoxic activity is related with the state of oxidation of compound.

Oxabicyclooctane-Linked Novel Bacterial Topoisomerase Inhibitors as Broad Spectrum Antibacterial Agents

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

Singh, Sheo B.; Kaelin, David E.; Wu, Jin

Bacterial resistance is eroding the clinical utility of existing antibiotics necessitating the discovery of new agents. Bacterial type II topoisomerase is a clinically validated, highly effective, and proven drug target. This target is amenable to inhibition by diverse classes of inhibitors with alternative and distinct binding sites to quinolone antibiotics, thus enabling the development of agents that lack cross-resistance to quinolones. Described here are novel bacterial topoisomerase inhibitors (NBTIs), which are a new class of gyrase and topo IV inhibitors and consist of three distinct structural moieties. The substitution of the linker moiety led to discovery of potent broad-spectrum NBTIsmore » with reduced off-target activity (hERG IC50 > 18 μM) and improved physical properties. AM8191 is bactericidal and selectively inhibits DNA synthesis and Staphylococcus aureus gyrase (IC50 = 1.02 μM) and topo IV (IC50 = 10.4 μM). AM8191 showed parenteral and oral efficacy (ED50) at less than 2.5 mg/kg doses in a S. aureus murine infection model. A cocrystal structure of AM8191 bound to S. aureus DNA-gyrase showed binding interactions similar to that reported for GSK299423, displaying a key contact of Asp83 with the basic amine at position-7 of the linker.« less

Genomics-Inspired Discovery of Three Antibacterial Active Metabolites, Aurantinins B, C, and D from Compost-Associated Bacillus subtilis fmb60.

PubMed

Yang, Jie; Zhu, Xiaoyu; Cao, Mingming; Wang, Changbao; Zhang, Chong; Lu, Zhaoxin; Lu, Fengxia

2016-11-23

Fmb60 is a wild-type Bacillus subtilis isolated from compost with significant broad-spectrum antimicrobial activities. Two novel PKS clusters were recognized in the genome sequence of fmb60, and then three polyene antibiotics, aurantinins B, C, and D, 1-3, were obtained by bioactivity-guided isolation from the fermentation of fmb60. The structures of aurantinins B-D were elucidated by LC-HRMS and NMR data analysis. Aurantinins C and D were identified as new antimicrobial compounds. The three aurantinins showed significant activity against multidrug-resistant Staphylococcus aureus and Clostridium sporogenes. However, aurantinins B-D did not exhibit any cytotoxicity (IC50 > 100 μg/mL) against LO2 and Caco2 cell lines by MTT assay. Furthermore, using S. aureus as a model bacterium to explore the antibacterial mechanism of aurantinins B-D, it was revealed that the bactericidal activity of aurantinins B-D was related to their ability to disrupt the cell membrane.

Hidden Broad-line Regions in Seyfert 2 Galaxies: From the Spectropolarimetric Perspective

NASA Astrophysics Data System (ADS)

Du, Pu; Wang, Jian-Min; Zhang, Zhi-Xiang

2017-05-01

The hidden broad-line regions (BLRs) in Seyfert 2 galaxies, which display broad emission lines (BELs) in their polarized spectra, are a key piece of evidence in support of the unified model for active galactic nuclei (AGNs). However, the detailed kinematics and geometry of hidden BLRs are still not fully understood. The virial factor obtained from reverberation mapping of type 1 AGNs may be a useful diagnostic of the nature of hidden BLRs in type 2 objects. In order to understand the hidden BLRs, we compile six type 2 objects from the literature with polarized BELs and dynamical measurements of black hole masses. All of them contain pseudobulges. We estimate their virial factors, and find the average value is 0.60 and the standard deviation is 0.69, which agree well with the value of type 1 AGNs with pseudobulges. This study demonstrates that (1) the geometry and kinematics of BLR are similar in type 1 and type 2 AGNs of the same bulge type (pseudobulges), and (2) the small values of virial factors in Seyfert 2 galaxies suggest that, similar to type 1 AGNs, BLRs tend to be very thick disks in type 2 objects.

Hidden Broad-line Regions in Seyfert 2 Galaxies: From the Spectropolarimetric Perspective

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

Du, Pu; Wang, Jian-Min; Zhang, Zhi-Xiang, E-mail: dupu@ihep.ac.cn

2017-05-01

The hidden broad-line regions (BLRs) in Seyfert 2 galaxies, which display broad emission lines (BELs) in their polarized spectra, are a key piece of evidence in support of the unified model for active galactic nuclei (AGNs). However, the detailed kinematics and geometry of hidden BLRs are still not fully understood. The virial factor obtained from reverberation mapping of type 1 AGNs may be a useful diagnostic of the nature of hidden BLRs in type 2 objects. In order to understand the hidden BLRs, we compile six type 2 objects from the literature with polarized BELs and dynamical measurements of blackmore » hole masses. All of them contain pseudobulges. We estimate their virial factors, and find the average value is 0.60 and the standard deviation is 0.69, which agree well with the value of type 1 AGNs with pseudobulges. This study demonstrates that (1) the geometry and kinematics of BLR are similar in type 1 and type 2 AGNs of the same bulge type (pseudobulges), and (2) the small values of virial factors in Seyfert 2 galaxies suggest that, similar to type 1 AGNs, BLRs tend to be very thick disks in type 2 objects.« less

Synthesis of novel amides based on acridone scaffold with interesting antineoplastic activity.

PubMed

Mahajan, Anand A; Rane, Rajesh A; Amritkar, Anish A; Naphade, Shital S; Miniyar, Pankaj B; Bangalore, Pavan Kumar; Karpoormath, Rajshekhar

2015-01-01

In search of novel cytotoxic agents based on acridone scaffold, twenty five derivatives of acridone-2- carboxamide were synthesized and evaluated against a panel of eleven cancer cell lines by using MTT assay. Amides, A5 and A8 (IC50 = 0.3 µM) exhibited good cytotoxicity against MCF7. Compound A22 (IC50 = 4.3 µM) was found to be selectively cytotoxic against cancer cell line MCF7 and KB403. Particularly, promising cytotoxic activities were shown by amides A6 (IC50 = 0.7 µM), A16 (IC50 = 6.3 µM), A8 (IC50 = 0.9 µM ), A21 (IC50 = 1.3 µM), A5 (IC50 = 2.9 µM), A8 (IC50 = 2.8 µM), A14 (IC50 = 0.8 µM), A9 (IC50 = 0.8 µM) and A8 (IC50 = 0.4 µM) against cell lines; PA1, WRL68, CaCO2, TK-10, K-562, PC-3, HOP-92, ECV-304 and UACC-257, respectively. The favorable cytotoxic profile and non-toxicity towards normal human cells displayed by the derivative revealed their potential for further anticancer drug developments.

Broad Hβ Emission-line Variability in a Sample of 102 Local Active Galaxies

NASA Astrophysics Data System (ADS)

Runco, Jordan N.; Cosens, Maren; Bennert, Vardha N.; Scott, Bryan; Komossa, S.; Malkan, Matthew A.; Lazarova, Mariana S.; Auger, Matthew W.; Treu, Tommaso; Park, Daeseong

2016-04-01

A sample of 102 local (0.02 ≤ z ≤ 0.1) Seyfert galaxies with black hole masses MBH > 107M⊙ was selected from the Sloan Digital Sky Survey (SDSS) and observed using the Keck 10 m telescope to study the scaling relations between MBH and host galaxy properties. We study profile changes of the broad Hβ emission line within the three to nine year time frame between the two sets of spectra. The variability of the broad Hβ emission line is of particular interest, not only because it is used to estimate MBH, but also because its strength and width are used to classify Seyfert galaxies into different types. At least some form of broad-line variability (in either width or flux) is observed in the majority (∼66%) of the objects, resulting in a Seyfert-type change for ∼38% of the objects, likely driven by variable accretion and/or obscuration. The broad Hβ line virtually disappears in 3/102 (∼3%) extreme cases. We discuss potential causes for these changing look active galactic nuclei. While similar dramatic transitions have previously been reported in the literature, either on a case-by-case basis or in larger samples focusing on quasars at higher redshifts, our study provides statistical information on the frequency of Hβ line variability in a sample of low-redshift Seyfert galaxies.

Metabolism of the tropine indole-3-carboxylate ICS 205-930 by differentiated rat and human hepatoma cells.

PubMed

Fischer, V; Baldeck, J P; Wiebel, F J

The metabolism of the tropine indole-3-carboxylate ICS 205-930 (ICS), a highly potent and selective antagonist of 5-HT3 receptors, was investigated in continuous cell lines derived from rat or human liver and compared to the in vivo metabolism in rat and human. The well-differentiated rat hepatoma line 2sFou extensively metabolized ICS by hydroxylation of the indole moiety and subsequent conjugation to form the corresponding glucuronides and sulfates. The 2sFou cells also oxidized ICS at the tropinyl moiety to form both N-demethyl and N-oxide derivatives. The relative amount of the various metabolites was dependent on the substrate concentration. Pretreatment of the cells with dexamethasone increased the rate of metabolism for all pathways, while benz[a]anthracene caused an increase in hydroxylation at the indole moiety at the expense of N-oxidation. Phenobarbital pretreatment had no effect on ICS metabolism. The pattern of metabolites formed in 2sFou cells was qualitatively similar to that formed in rat urine. The human hepatoma line HepG2 metabolized ICS only to a small extent. The HepG2 cells failed to form detectable amounts of ICS conjugates found in human urine. The N-oxide-ICS was not found in HepG2 cells or in human urine. Virtually no ICS metabolites were found in human lung adenocarcinoma lines NCI-H358 or NCI-H322. The results suggest that continuous cell lines such as the differentiated rat hepatoma cells 2sFou might be used to mimic the metabolism of xenobiotics in rat and to clarify their complex metabolic pathways.

Multi-colored immunochromatography using nanobeads for rapid and sensitive typing of seasonal influenza viruses.

PubMed

Sakurai, Akira; Takayama, Katsuyoshi; Nomura, Namiko; Yamamoto, Naoki; Sakoda, Yoshihiro; Kobayashi, Yukuharu; Kida, Hiroshi; Shibasaki, Futoshi

2014-12-01

Immunochromatography (IC) is an antigen-detection assay that plays an important role in the rapid diagnosis of influenza viruses because of its rapid turnaround and ease of use. Despite the usefulness of IC, the limit of detection of common IC kits is as high as 10(3)-10(4) plaque forming units (pfu) per reaction, resulting in their limited sensitivities. Early diagnosis within 24h would provide more appropriate timing of treatment. In this study, a multi-colored NanoAct™ bead IC was established to detect seasonal influenza viruses. This method has approximately 10-fold higher sensitivity than that of colloidal gold or colored latex bead IC assays, and does not require specific instruments. More notably, NanoAct™ bead IC can distinguish influenza A and B viruses from clinical samples with a straightforward readout composed of colored lines. Our results will provide new strategies for the diagnosis, treatment, and a chance to survey of influenza viruses in developing countries and in the field research. Copyright © 2014 Elsevier B.V. All rights reserved.

On the origin of a very close similarity between the spectra of the supernova type 1 in NGC 3198 and the absorption of DQ HeR

NASA Technical Reports Server (NTRS)

Mustel, E. R.

1979-01-01

The type 1 supernova discovered late in 1966 in NGC 3198 has broad minima in its spectrum break down into a number of significantly narrower absorption bands. The broad minima of tau, sigma and mu, which usually show no details in the spectra of type supernovas, contain a number of narrow absorption bands. The reality of most of these absorption bands is demonstrated by comparison of recordings of spectra of the supernova presented for two moments in time. These minima (particularly of tau and mu,) are a result of blending of several broad absorption bands. The minimum of tau should be a blend of intensive and very broad Fe absorption lines, in which the lower level is metastable. The wavelengths of these line are: 5169, 5198, 5235, 5276, 5317, 5363A.

Altered temporal lobe white matter lipid ion profiles in an experimental model of sporadic Alzheimer's disease.

PubMed

Tong, Ming; Leão, Raiane; Vimbela, Gina V; Yalcin, Emine B; Kay, Jared; Krotow, Alexander; de la Monte, Suzanne M

2017-07-01

White matter is an early and important yet under-evaluated target of Alzheimer's disease (AD). Metabolic impairments due to insulin and insulin-like growth factor resistance contribute to white matter degeneration because corresponding signal transduction pathways maintain oligodendrocyte function and survival. This study utilized a model of sporadic AD in which adult Long Evans rats administered intracerebral streptozotocin (i.c. STZ) developed AD-type neurodegeneration. Temporal lobe white matter lipid ion profiles were characterized by matrix-assisted laser desorption/ionization-imaging mass spectrometry (MALDI-IMS). Although the lipid ion species expressed in the i.c. STZ and control groups were virtually identical, i.c. STZ mainly altered the abundances of various lipid ions. Correspondingly, the i.c. STZ group was distinguished from control by principal component analysis and data bar plots. i.c. STZ mainly reduced expression of lipid ions with low m/z's (less than 810) as well as the upper range m/z lipids (m/z 964-986), and increased expression of lipid ions with m/z's between 888 and 937. Phospholipids were mainly included among the clusters inhibited by i.c. STZ, while both sulfatides and phospholipids were increased by i.c. STZ. However, Chi-Square analysis demonstrated significant i.c. STZ-induced trend reductions in phospholipids and increases in sulfatides (P<0.00001). The i.c. STZ model of sporadic AD is associated with broad and sustained abnormalities in temporal lobe white matter lipids. The findings suggest that the i.c. STZ model could be used for pre-clinical studies to assess therapeutic measures for their ability to restore white matter integrity in AD. Copyright © 2017 Elsevier Inc. All rights reserved.

Preclinical efficacy of the MDM2 inhibitor RG7112 in MDM2 amplified and TP53 wild-type glioblastomas

PubMed Central

Verreault, Maite; Schmitt, Charlotte; Goldwirt, Lauriane; Pelton, Kristine; Haidar, Samer; Levasseur, Camille; Guehennec, Jeremy; Knoff, David; Labussiere, Marianne; Marie, Yannick; Ligon, Azra H.; Mokhtari, Karima; Hoang-Xuan, Khe; Sanson, Marc; Alexander, Brian M; Wen, Patrick Y.; Delattre, Jean-Yves; Ligon, Keith L.; Idbaih, Ahmed

2016-01-01

Rationale p53 pathway alterations are key molecular events in glioblastoma (GBM). MDM2 inhibitors increase expression and stability of p53 and are presumed to be most efficacious in patients with TP53 wild-type and MDM2-amplified cancers. However, this biomarker hypothesis has not been tested in patients or patient-derived models for GBM. Methods We performed a preclinical evaluation of RG7112 MDM2 inhibitor, across a panel of 36 patient-derived GBM cell lines (PDCLs), each genetically characterized according to their P53 pathway status. We then performed a pharmacokinetic (PK) profiling of RG7112 distribution in mice and evaluated the therapeutic activity of RG7112 in orthotopic and subcutaneous GBM models. Results MDM2-amplified PDCLs were 44 times more sensitive than TP53 mutated lines that showed complete resistance at therapeutically attainable concentrations (avg. IC50 of 0.52 μM vs 21.9 μM). MDM4 amplified PDCLs were highly sensitive but showed intermediate response (avg. IC50 of 1.2 μM), whereas response was heterogeneous in TP53 wild-type PDCLs with normal MDM2/4 levels (avg. IC50 of 7.7 μM). In MDM2-amplified lines, RG7112 restored p53 activity inducing robust p21 expression and apoptosis. PK profiling of RG7112-treated PDCL intracranial xenografts demonstrated that the compound significantly crosses the blood-brain and the blood-tumor barriers. Most importantly, treatment of MDM2-amplified/TP53 wild-type PDCL-derived model (subcutaneous and orthotopic) reduced tumor growth, was cytotoxic, and significantly increased survival. Conclusion These data strongly support development of MDM2 inhibitors for clinical testing in MDM2-amplified GBM patients. Moreover, significant efficacy in a subset of non-MDM2 amplified models suggests that additional markers of response to MDM2 inhibitors must be identified. PMID:26482041

BROAD Hβ EMISSION-LINE VARIABILITY IN A SAMPLE OF 102 LOCAL ACTIVE GALAXIES

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

Runco, Jordan N.; Cosens, Maren; Bennert, Vardha N.

2016-04-10

A sample of 102 local (0.02 ≤ z ≤ 0.1) Seyfert galaxies with black hole masses M{sub BH} > 10{sup 7}M{sub ⊙} was selected from the Sloan Digital Sky Survey (SDSS) and observed using the Keck 10 m telescope to study the scaling relations between M{sub BH} and host galaxy properties. We study profile changes of the broad Hβ emission line within the three to nine year time frame between the two sets of spectra. The variability of the broad Hβ emission line is of particular interest, not only because it is used to estimate M{sub BH}, but also because its strengthmore » and width are used to classify Seyfert galaxies into different types. At least some form of broad-line variability (in either width or flux) is observed in the majority (∼66%) of the objects, resulting in a Seyfert-type change for ∼38% of the objects, likely driven by variable accretion and/or obscuration. The broad Hβ line virtually disappears in 3/102 (∼3%) extreme cases. We discuss potential causes for these changing look active galactic nuclei. While similar dramatic transitions have previously been reported in the literature, either on a case-by-case basis or in larger samples focusing on quasars at higher redshifts, our study provides statistical information on the frequency of Hβ line variability in a sample of low-redshift Seyfert galaxies.« less

Novel AlInN/GaN integrated circuits operating up to 500 °C

NASA Astrophysics Data System (ADS)

Gaska, R.; Gaevski, M.; Jain, R.; Deng, J.; Islam, M.; Simin, G.; Shur, M.

2015-11-01

High electron concentration in 2DEG channel of AlInN/GaN devices is remarkably stable over a broad temperature range, enabling device operation above 500 °C. The developed IC technology is based on three key elements: (1) exceptional quality AlInN/GaN heterostructure with very high carrier concentration and mobility enables IC fast operation in a broad temperature range; (2) heterostructure field effect transistor approach t provides fully planar IC structure which is easy to scale and to combine with the other high temperature electronic components; (3) fabrication advancements including novel metallization scheme and high-K passivation/gate dielectrics enable high temperature operation. The feasibility of the developed technology was confirmed by fabrication and testing of the high temperature inverter and differential amplifier ICs using AlInN/GaN heterostructures. The developed ICs showed stable performance with unit-gain bandwidth above 1 MHz and internal response time 45 ns at temperatures as high as 500 °C.

Ultra-High Performance, High-Temperature Superconducting Wires via Cost-effective, Scalable, Co-evaporation Process

PubMed Central

Kim, Ho-Sup; Oh, Sang-Soo; Ha, Hong-Soo; Youm, Dojun; Moon, Seung-Hyun; Kim, Jung Ho; Dou, Shi Xue; Heo, Yoon-Uk; Wee, Sung-Hun; Goyal, Amit

2014-01-01

Long-length, high-temperature superconducting (HTS) wires capable of carrying high critical current, Ic, are required for a wide range of applications. Here, we report extremely high performance HTS wires based on 5 μm thick SmBa2Cu3O7 − δ (SmBCO) single layer films on textured metallic templates. SmBCO layer wires over 20 meters long were deposited by a cost-effective, scalable co-evaporation process using a batch-type drum in a dual chamber. All deposition parameters influencing the composition, phase, and texture of the films were optimized via a unique combinatorial method that is broadly applicable for co-evaporation of other promising complex materials containing several cations. Thick SmBCO layers deposited under optimized conditions exhibit excellent cube-on-cube epitaxy. Such excellent structural epitaxy over the entire thickness results in exceptionally high Ic performance, with average Ic over 1,000 A/cm-width for the entire 22 meter long wire and maximum Ic over 1,500 A/cm-width for a short 12 cm long tape. The Ic values reported in this work are the highest values ever reported from any lengths of cuprate-based HTS wire or conductor. PMID:24752189

Cytotoxic constituents from Brazilian red propolis and their structure-activity relationship.

PubMed

Li, Feng; Awale, Suresh; Tezuka, Yasuhiro; Kadota, Shigetoshi

2008-05-15

Several classes of flavonoids [flavanoids (1-10), flavonol (11), isoflavones (12-18), isoflavanones (19-22), isoflavans (23-26), chalcones (27-30), auronol (31), pterocarpans (32-37), 2-arylbenzofuran (38), and neoflavonoid (39)] and lignans (40-42) isolated from the MeOH extract of Brazilian red propolis were investigated for their cytotoxic activity against a panel of six different cancer cell lines including murine colon 26-L5 carcinoma, murine B16-BL6 melanoma, murine Lewis lung carcinoma, human lung A549 adenocarcinoma, human cervix HeLa adenocarcinoma, and human HT-1080 fibrosarcoma cell lines. Based on the observed results, structure-activity relationships were discussed. Among the tested compounds, 7-hydroxy-6-methoxyflavanone (3) exhibited the most potent activity against B16-BL6 (IC(50), 6.66microM), LLC (IC(50), 9.29microM), A549 (IC(50), 8.63microM), and HT-1080 (IC(50), 7.94microM) cancer cell lines, and mucronulatol (26) against LLC (IC(50), 8.38microM) and A549 (IC(50), 9.9microM) cancer cell lines. These activity data were comparable to those of the clinically used anticancer drugs, 5-fluorouracil and doxorubicin, against the tested cell lines, suggesting that 3 and 26 are the good candidates for future anticancer drug development.

Discovery of a Broad-Spectrum Antiviral Compound That Inhibits Pyrimidine Biosynthesis and Establishes a Type 1 Interferon-Independent Antiviral State

PubMed Central

Adcock, Robert S.; Schroeder, Chad E.; Chu, Yong-Kyu; Sotsky, Julie B.; Cramer, Daniel E.; Chilton, Paula M.; Song, Chisu; Anantpadma, Manu; Davey, Robert A.; Prodhan, Aminul I.; Yin, Xinmin; Zhang, Xiang

2016-01-01

Viral emergence and reemergence underscore the importance of developing efficacious, broad-spectrum antivirals. Here, we report the discovery of tetrahydrobenzothiazole-based compound 1, a novel, broad-spectrum antiviral lead that was optimized from a hit compound derived from a cytopathic effect (CPE)-based antiviral screen using Venezuelan equine encephalitis virus. Compound 1 showed antiviral activity against a broad range of RNA viruses, including alphaviruses, flaviviruses, influenza virus, and ebolavirus. Mechanism-of-action studies with metabolomics and molecular approaches revealed that the compound inhibits host pyrimidine synthesis and establishes an antiviral state by inducing a variety of interferon-stimulated genes (ISGs). Notably, the induction of the ISGs by compound 1 was independent of the production of type 1 interferons. The antiviral activity of compound 1 was cell type dependent with a robust effect observed in human cell lines and no observed antiviral effect in mouse cell lines. Herein, we disclose tetrahydrobenzothiazole compound 1 as a novel lead for the development of a broad-spectrum, antiviral therapeutic and as a molecular probe to study the mechanism of the induction of ISGs that are independent of type 1 interferons. PMID:27185801

Chemical constituents from rhizome of Anemone amurensis.

PubMed

Lv, Chong-Ning; Li, Yan-Jiao; Wang, Jing; Qin, Ru-Lan; Lei, Tian-Li; Lu, Jin-Cai

2016-07-01

Phytochemical investigation of the 70% EtOH extract of the rhizome of Anemone amurensis led to the isolation of two new oleanane-type triterpenoid saponins 1 and 2. Their structures were elucidated on the basis of chemical and spectral analysis, including 1D, 2D NMR data, and HR-ESI-MS. Compounds 1 and 2 were tested for cytotoxicities against two human cancer cell lines (A549 and Hep-G2). Compound 2 showed potent cytotoxicity with IC50 values of 38.53 and 66.17 μM, respectively, while compound 1 with IC50 > 100 μM.

Carfilzomib demonstrates broad anti-tumor activity in pre-clinical non-small cell and small cell lung cancer models.

PubMed

Baker, Amanda F; Hanke, Neale T; Sands, Barbara J; Carbajal, Liliana; Anderl, Janet L; Garland, Linda L

2014-12-31

Carfilzomib (CFZ) is a proteasome inhibitor that selectively and irreversibly binds to its target and has been approved in the US for treatment of relapsed and refractory multiple myeloma. Phase 1B studies of CFZ reported signals of clinical activity in solid tumors, including small cell lung cancer (SCLC). The aim of this study was to investigate the activity of CFZ in lung cancer models. A diverse panel of human lung cancer cell lines and a SHP77 small cell lung cancer xenograft model were used to investigate the anti-tumor activity of CFZ. CFZ treatment inhibited both the constitutive proteasome and the immunoproteasome in lung cancer cell lines. CFZ had marked anti-proliferative activity in A549, H1993, H520, H460, and H1299 non-small cell lung cancer (NSCLC) cell lines, with IC50 values after 96 hour exposure from <1.0 nM to 36 nM. CFZ had more variable effects in the SHP77 and DMS114 SCLC cell lines, with IC50 values at 96 hours from <1 nM to 203 nM. Western blot analysis of CFZ-treated H1993 and SHP77 cells showed cleavage of poly ADP ribose polymerase (PARP) and caspase-3, indicative of apoptosis, and induction of microtubule-associated protein-1 light chain-3B (LC3B), indicative of autophagy. In SHP77 flank xenograft tumors, CFZ monotherapy inhibited tumor growth and prolonged survival, while no additive or synergistic anti-tumor efficacy was observed for CFZ + cisplatin (CDDP). CFZ demonstrated anti-proliferative activity in lung cancer cell lines in vitro and resulted in a significant survival advantage in mice with SHP77 SCLC xenografts, supporting further pre-clinical and clinical investigations of CFZ in NSCLC and SCLC.

Comparison of ion chromatographic methods based on conductivity detection, post-column-reaction and on-line-coupling IC-ICP-MS for the determination of bromate.

PubMed

Schminke, G; Seubert, A

2000-02-01

An established method for the determination of the disinfection by-product bromate is ion chromatography (IC). This paper presents a comparison of three IC methods based on either conductivity detection (IC-CD), a post-column-reaction (IC-PCR-VIS) or the on-line-coupling with inductively coupled plasma mass spectrometry (IC-ICP-MS). Main characteristics of the methods such as method detection limits (MDL), time of analysis and sample pretreatment are compared and applicability for routine analysis is critically discussed. The most sensitive and rugged method is IC-ICP-MS, followed by IC-PCR-VIS. The photometric detection is subject to a minor interference in real world samples, presumably caused by carbonate. The lowest sensitivity is shown by the IC-CD method as slowest method compared, which, in addition, requires a sample pretreatment. The highest amount of information is delivered by IC-PCR-VIS, which allows the simultaneous determination of the seven standard anions and bromate.

Taking advantage of public reporting: An infection composite score to assist evaluating hospital performance for infection prevention efforts.

PubMed

Fakih, Mohamad G; Skierczynski, Boguslow; Bufalino, Angelo; Groves, Clariecia; Roberts, Phillip; Heavens, Michelle; Hendrich, Ann; Haydar, Ziad

2016-12-01

The standardized infection ratio (SIR) evaluates individual publicly reported health care-associated infections, but it may not assess overall performance. We piloted an infection composite score (ICS) in 82 hospitals of a single health system. The ICS is a combined score for central line-associated bloodstream infections, catheter-associated urinary tract infections, colon and abdominal hysterectomy surgical site infections, and hospital-onset methicillin-resistant Staphylococcus aureus bacteremia and Clostridium difficile infections. Individual facility ICSs were calculated by normalizing each of the 6 SIR events to the system SIR for baseline and performance periods (ICS ib and ICS ip , respectively). A hospital ICS ib reflected its baseline performance compared with system baseline, whereas a ICS ip provided information of its outcome changes compared with system baseline. Both the ICS ib (baseline 2013) and ICS ip (performance 2014) were calculated for 63 hospitals (reporting at least 4 of the 6 event types). The ICS ip improved in 36 of 63 (57.1%) hospitals in 2014 when compared with the ICS ib in 2013. The ICS ib 2013 median was 0.96 (range, 0.13-2.94) versus the 2014 ICS ip median of 0.92 (range, 0-6.55). Variation was more evident in hospitals with ≤100 beds. The system performance score (ICS sp ) in 2014 was 0.95, a 5% improvement compared with 2013. The proposed ICS may help large health systems and state hospital associations better evaluate key infectious outcomes, comparing them with historic and concurrent performance of peers. Copyright © 2016 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

Teachers' Perspectives: Factors That Impact Implementation of Integrated Curriculum in K-3 Classrooms

ERIC Educational Resources Information Center

Fu, Yao; Sibert, Susan

2017-01-01

The purpose of this study was to uncover the factors that may influence K-3 in-service teachers' implementation of integrated curriculum (IC). To provide a consistent research base, the broad definition of IC and Jacob's model were adopted to clarify the controversial concept of IC. Survey data were collected from forty-two teachers from ten…

Investigating the properties of low-mass AGN and their connection to unification models

NASA Astrophysics Data System (ADS)

Hood, Carol Elizabeth

The most basic model of active galactic nuclei (AGN) suggest the observational differences between Type 1 and Type 2 objects are solely due to the orientation angle of the object. Although there are still some unanswered questions about the structures surrounding the central engines of the AGN, such as if the obscuring region is due to a dusty torus or an outflowing wind, observations (e.g. the detections of broad lines in the polarized light of some Type 2 objects) have proved consistent with predictions and continue to strengthen the case for unification. However, many are still searching for "true" Type 2 objects. These objects optically look like other Type 2 objects, but instead of having their broad line region blocked from the line-of-sight by the obscuring region, they are believed to lack the broad line region altogether. Others have predicted that at low luminosity or low accretion rate, the broad line region will disappear, leaving all objects to optically look like Type 2 objects, despite their level of intrinsic absorption. Low-mass (< 10^6 solar masses) AGN provide interesting environments in which these unification models can be studied. We present an in-depth multi-wavelength study of one of the prototypical low-mass AGN, POX 52, investigating the properties of the central engine along with that of the host galaxy. In addition, we examine the X-ray properties of a sample of Type 2 objects observed with XMM-Newton and the IR properties of a sample of both Type 1 and 2 objects observed with the Spitzer Infrared Spectrograph, in order to study the absorption properties of these objects and test the validity of unification models in the low-mass regime. We find little to no evidence of any "true" Type 2 objects in any of our samples, and show that in all tests preformed, low-mass AGN appear to simply be scaled-down versions of their more massive counterparts, keeping current unification models intact down to the lowest black hole masses probed to date.

Exploring possible relations between optical variability time scales and broad emission line shapes in AGN

NASA Astrophysics Data System (ADS)

Bon, Edi; Jovanović, Predrag; Marziani, Paola; Bon, Nataša; Otašević, Aleksandar

2018-06-01

Here we investigate the connection of broad emission line shapes and continuum light curve variability time scales of type-1 Active Galactic Nuclei (AGN). We developed a new model to describe optical broad emission lines as an accretion disk model of a line profile with additional ring emission. We connect ring radii with orbital time scales derived from optical light curves, and using Kepler's third law, we calculate mass of central supermassive black hole (SMBH). The obtained results for central black hole masses are in a good agreement with other methods. This indicates that the variability time scales of AGN may not be stochastic, but rather connected to the orbital time scales which depend on the central SMBH mass.

Variable broad lines and outflow in the weak blazar PBC J2333.9-2343

NASA Astrophysics Data System (ADS)

Hernández-García, L.; Vietri, G.; Panessa, F.; Piconcelli, E.; Chavushyan, V.; Jiménez-Andrade, E. F.; Bassani, L.; Bazzano, A.; Cazzoli, S.; Malizia, A.; Masetti, N.; Monaco, L.; Pović, M.; Saviane, I.; Ubertini, P.

2018-05-01

PBC J2333.9-2343 is a peculiar active nucleus with two giant radio lobes and a weak blazar-like nucleus at their center. In the present work we show new optical, UV, and X-ray data taken from the San Pedro Mártir telescope, the New Technology Telescope, NTT/EFOSC2, and the Swift/XRT satellite. The source is highly variable at all frequencies, in particular the strongest variations are found in the broad Hα component with a flux increase of 61±4 per cent between 2009 and 2016, following the X-ray flux increase of 62±6 per cent between 2010 and 2016. We also detected a broad Hβ component in 2016, making the optical classification change from type 1.9 to type 1.8 in one year. We have also detected a broad component of the [OIII]λ5007 line, which is blue-shifted and of high velocity, suggesting an origin from a highly disturbed medium, possibly an outflow. The line flux variability and broad widths are indicative of a jet that is, at least in part, responsible for the ionization of the BLR and NLR.

A KPC-scale X-ray jet in the BL LAC Source S5 2007+777

NASA Technical Reports Server (NTRS)

Sambruna, Rita; Maraschi, Laura; Tavecchio, Fabrizio

2008-01-01

The BL Lac S3 2007++777, a classical radio-selected BL Lac from the sample of Stirkel et al. exhibiting an extended (19") radio jet. was observed with Chandra revealing an X-ray jet with simi1ar morphology. The hard X-ray spectrum and broad band SED is consistent with an IC/CMB origin for the X-ray emission, implying a highly relativistic flow at small angle to the line of sight with an unusually large deprojected length, 300 kpc. A structured jet consisting of a fast spine and slow wall is consistent with the observations.

SN 2013dx associated with GRB 130702A: a detailed photometric and spectroscopic monitoring and a study of the environment

NASA Astrophysics Data System (ADS)

D'Elia, Valerio

2015-08-01

Long duration gamma-ray bursts (GRBs) and broad-line, type Ic supernovae (SNe) are strongly connected. We aim at characterizing SN 2013dx, associated with GRB 130702A, through sensitive and extensive ground-based observational campaigns in the optical-IR band.We monitored the field of the Swift GRB 130702A (redshift z = 0.145) using the 8.2-m VLT, the 3.6-m TNG and the 0.6-m REM telescopes during the time interval between 4 and 40 days after the burst. Photometric and spectroscopic observations revealed the presence of the associated Type Ic SN 2013dx. Our multi-band photometry allowed the construction of a bolometric light curve.The bolometric light curve of SN 2013dx resembles that of 2003dh (associated with GRB 030329), but is ~ 10% faster and ~25% dimmer. From this we infer a synthesized 56Ni mass of ~0.3 solar masses. The multi-epoch optical spectroscopy shows that the SN 2013dx behavior is best matched by SN 1998bw, among the other well-known low-z SNe associated with GRBs and XRFs, and by SN 2010ah, an energetic Type Ic SN not associated with any GRB. The photospheric velocity of the ejected material declines from ~ 2.7 X10^4 km/s at 8 rest frame days from the explosion, to ~3.5X103 km/s at 40 days. These values are extremely close to those of SN1998bw and 2010ah. We deduce for SN 2013dx a kinetic energy of (32 +/- 9)X10^51 erg, and an ejected mass of 7 +/- 1 solar masses. This suggests that the progenitor of SN2013dx had a mass of ~25 solar masses, i.e., 15-20% less massive than that of SN 1998bw.Finally, we perfom a study of the SN 2013dx environment, through spectroscopy of the closeby galaxies. 9 out of the 14 inspected galaxies lie within 0.03 in redshift from z=0.145, indicating that the host of GRB 130702A/SN 2013dx belongs to a group of galaxies, an unprecedented finding for a GRB-associated SN and, to our knowledge, for long GRBs in general.

Survey of Water and Ammonia in Nearby Galaxies (SWAN): Resolved Ammonia Thermometry and Water and Methanol Masers in IC 342, NGC 6946, and NGC 2146

NASA Astrophysics Data System (ADS)

Gorski, Mark; Ott, Jürgen; Rand, Richard; Meier, David S.; Momjian, Emmanuel; Schinnerer, Eva

2018-04-01

The Survey of Water and Ammonia in Nearby galaxies (SWAN) studies atomic and molecular species across the nuclei of four star-forming galaxies: NGC 253, IC 342, NGC 6946, and NGC 2146. As part of this survey, we present Karl G. Jansky Very Large Array molecular line observations of three galaxies: IC 342, NGC 6946, and NGC 2146. NGC 253 is covered in a previous paper. These galaxies were chosen to span an order of magnitude in star formation rates and to select a variety of galaxy types. We target the metastable transitions of ammonia NH3(1, 1) to (5, 5), the 22 GHz water (H2O) (616–523) transition, and the 36.1 GHz methanol (CH3OH) (4‑1–30) transition. We use the NH3 metastable lines to perform thermometry of the dense molecular gas. We show evidence for uniform heating across the central kiloparsec of IC 342 with two temperature components for the molecular gas, similar to NGC 253, of 27 and 308 K, and that the dense molecular gas in NGC 2146 has a temperature <86 K. We identify two new water masers in IC 342, and one new water maser in each of NGC 6946 and NGC 2146. The two galaxies NGC 253 and NGC 2146, with the most vigorous star formation, host H2O kilomasers. Lastly, we detect the first 36 GHz CH3OH masers in IC 342 and NGC 6946. For the four external galaxies the total CH3OH luminosity in each galaxy suggests a correlation with galactic star formation rate, whereas the morphology of the emission is similar to that of HNCO, a weak shock tracer.

Evidence for active galactic nucleus feedback in the broad absorption lines and reddening of MRK 231 {sup ,}

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

Leighly, Karen M.; Baron, Eddie; Lucy, Adrian B.

2014-06-20

We present the first J-band spectrum of Mrk 231, which reveals a large He I* λ10830 broad absorption line with a profile similar to that of the well-known Na I broad absorption line. Combining this spectrum with optical and UV spectra from the literature, we show that the unusual reddening noted by Veilleux et al. is explained by a reddening curve like those previously used to explain low values of total-to-selective extinction in Type Ia supernovae. The nuclear starburst may be the origin and location of the dust. Spatially resolved emission in the broad absorption line trough suggests nearly fullmore » coverage of the continuum emission region. The broad absorption lines reveal higher velocities in the He I* lines (produced in the quasar-photoionized H II region) compared with the Na I and Ca II lines (produced in the corresponding partially ionized zone). Cloudy simulations show that a density increase is required between the H II and partially ionized zones to produce ionic column densities consistent with the optical and IR absorption line measurements and limits, and that the absorber lies ∼100 pc from the central engine. These results suggest that the He I* lines are produced in an ordinary quasar BAL wind that impacts upon, compresses, and accelerates the nuclear starburst's dusty effluent (feedback in action), and the Ca II and Na I lines are produced in this dusty accelerated gas. This unusual circumstance explains the rarity of Na I absorption lines; without the compression along our line of sight, Mrk 231 would appear as an ordinary iron low-ionization, broad absorption line quasar.« less

A Photometric Study of the Eclipsing Binary NSV 1000

NASA Astrophysics Data System (ADS)

Richards, T. J.; Bembrick, C. S.

2018-06-01

Abstract NSV 1000 is an unstudied eclipsing binary in Hydrus. Our photometric research in the period 2014-2016 shows it is a W UMa system with a period of 0.336 579 6(3) d, consistent with the catalogued period. Model fitting to our B, V, and Ic light curves shows the two stars are barely in contact. The parameters derived from the fit satisfy the broadly defined characteristics of a W-type W UMa system.

CS in nearby galaxies: Distribution, kinematics, and multilevel studies

NASA Technical Reports Server (NTRS)

Mauersberger, R.; Henkel, Christian

1990-01-01

As a result of observations at the Institute for Radio Astronomy in the Millimeter Range (IRAM) 30-m telescope, maps of the distribution of the J = 2-1 transition of CS toward the galaxies IC 342 and NGC 253 are presented. The distribution of the CS emission from NGC 253 is consistent with the CO 1-0 line. The distribution of the CS emission from IC 342, however, resembles more that seen in the CO 3-2 line. For the first time, the detection of the isotopic substitution C-34S is reported toward an external galaxy: The C-34S 2-1 line has been detected toward NGC 253 and M 82 and the C-34S line has been detected tentatively toward M 82. Also for the first time, extragalactic CS has been observed in the 3-2 (toward NGC 253, IC 342 and M 82) and 5-4 (NGC 253 and IC 342) transitions.

An Investigation of the Growth Inhibitory Capacity of Several Medicinal Plants From Iran on Tumor Cell Lines

PubMed Central

Esmaeilbeig, Maryam; Kouhpayeh, Seyed Amin; Amirghofran, Zahra

2015-01-01

Background: Traditional herbal medicine is a valuable resource that provides new drugs for cancer treatment. Objectives: In this study we aim to screen and investigate the in vitro anti-tumor activities of ten species of plants commonly grown in Southern Iran. Materials and Methods: We used the MTT colorimetric assay to evaluate the cytotoxic activities of the methanol extracts of these plants on various tumor cell lines. The IC50 was calculated as a scale for this evaluation. Results: Satureja bachtiarica, Satureja hortensis, Thymus vulgaris, Thymus daenensis and Mentha lonigfolia showed the inhibitoriest effects on Jurkat cells with > 80% inhibition at 200 µg/mL. Satureja hortensis (IC50: 66.7 µg/mL) was the most effective. These plants also strongly inhibited K562 cell growth; Satureja bachtiarica (IC50: 28.3 µg/mL), Satureja hortensis (IC50: 52 µg/mL) and Thymus vulgaris (IC50: 87 µg/mL) were the most effective extracts. Cichorium intybus, Rheum ribes, Alhagi pseudalhagi and Glycyrrihza glabra also showed notable effects on the leukemia cell lines. The Raji cell line was mostly inhibited by Satureja bachtiarica and Thymus vulgaris with approximately 40% inhibition at 200µg/ml. The influence of these extracts on solid tumor cell lines was not strong. Fen cells were mostly affected by Glycyrrihza glabra (IC50: 182 µg/mL) and HeLa cells by Satureja hortensis (31.6% growth inhibitory effect at 200 µg/mL). Conclusions: Leukemic cell lines were more sensitive to the extracts than the solid tumor cell lines; Satureja hortensis, Satureja bachtiarica, Thymus vulgaris, Thymus daenensis and Mentha lonigfolia showed remarkable inhibitory potential. PMID:26634114

Leucocontextins A-R, lanostane-type triterpenoids from Ganoderma leucocontextum.

PubMed

Zhao, Zhen-Zhu; Chen, He-Ping; Li, Zheng-Hui; Dong, Ze-Jun; Bai, Xue; Zhou, Zhong-Yu; Feng, Tao; Liu, Ji-Kai

2016-03-01

Eighteen new lanostane-type triterpenoids, namely leucocontextins A-R (1-18) were isolated from the fruiting bodies of Ganoderma leucocontextum. Their structures were established by 1D and 2D NMR data in conjunction with HRESIMS/HREIMS, X-ray single crystal diffraction analysis. Compound 18 exhibited weak cytotoxicity against K562 and MCF-7 cell lines with IC50 of 20-30 μM. Copyright © 2015 Elsevier B.V. All rights reserved.

Cytotoxic triterpenoid saponins from Clematis tangutica.

PubMed

Zhao, Min; Da-Wa, Zhuo-Ma; Guo, Da-Le; Fang, Dong-Mei; Chen, Xiao-Zhen; Xu, Hong-Xi; Gu, Yu-Cheng; Xia, Bing; Chen, Lei; Ding, Li-Sheng; Zhou, Yan

2016-10-01

Eight previously undescribed oleanane-type triterpenoid saponins, clematangoticosides A-H, together with eight known saponins, were isolated from the whole plants of Clematis tangutica (Maxim.) Korsh. Their structures were elucidated by extensive spectroscopic analysis, in combination with chemical methods (acid hydrolysis and mild alkaline hydrolysis). Clematangoticosides D-G were found to be unusual 23, 28-bidesmosidic glycosides. The cytotoxic activities of all of the isolated saponins were evaluated against the four human cancer cell lines SGC-7901, HepG2, HL-60 and U251MG. Clematoside S, sapindoside B, kalopanax saponin A, and koelreuteria saponin A exhibited cytotoxicity against all of the test cancer cell lines with IC50 values in the range of 1.88-27.20 μM, while clematangoticoside D and F showed selective cytotoxicity against SGC-7901 with IC50 values of 24.22 and 21.35 μM, respectively. Copyright © 2016 Elsevier Ltd. All rights reserved.

The ionized gas at the centre of IC 10: a possible localized chemical pollution by Wolf-Rayet stars

NASA Astrophysics Data System (ADS)

López-Sánchez, Á. R.; Mesa-Delgado, A.; López-Martín, L.; Esteban, C.

2011-03-01

We present results from integral field spectroscopy with the Potsdam Multi-Aperture Spectrograph at the 3.5-m telescope at Calar Alto Observatory of the intense star-forming region [HL90] 111 at the centre of the starburst galaxy IC 10. We have obtained maps with a spatial sampling of 1 × 1 arcsec2= 3.9× 3.9 pc2 of different emission lines and analysed the extinction, physical conditions, nature of the ionization and chemical abundances of the ionized gas, as well determined locally the age of the most recent star formation event. By defining several apertures, we study the main integrated properties of some regions within [HL90] 111. Two contiguous spaxels show an unambiguous detection of the broad He IIλ4686 emission line, this feature seems to be produced by a single late-type WN star. We also report a probable N and He enrichment in the precise spaxels where the Wolf-Rayet (WR) features are detected. The enrichment pattern is roughly consistent with that expected for the pollution of the ejecta of a single or a very small number of WR stars. Furthermore, this chemical pollution is very localized (˜2 arcsec ˜7.8 pc) and it should be difficult to detect in star-forming galaxies beyond the Local Volume. We also discuss the use of the most common empirical calibrations to estimate the oxygen abundances of the ionized gas in nearby galaxies from 2D spectroscopic data. The ionization degree of the gas plays an important role when applying these empirical methods, as they tend to give lower oxygen abundances with increasing ionization degree. Based on observations collected at the Centro Astrónomico Hispano Alemán (CAHA) at Calar Alto, operated jointly by the Max-Plank Institut für Astronomie and the Instituto de Astrofísica de Andalucía (CSIC).Visiting Astronomer at the Instituto de Astrofísica de Canarias.

A New Black Hole Mass Estimate for Obscured Active Galactic Nuclei

NASA Astrophysics Data System (ADS)

Minezaki, Takeo; Matsushita, Kyoko

2015-04-01

We propose a new method for estimating the mass of a supermassive black hole, applicable to obscured active galactic nuclei (AGNs). This method estimates the black hole mass using the width of the narrow core of the neutral FeKα emission line in X-rays and the distance of its emitting region from the black hole based on the isotropic luminosity indicator via the luminosity scaling relation. Assuming the virial relation between the locations and the velocity widths of the neutral FeKα line core and the broad Hβ emission line, the luminosity scaling relation of the neutral FeKα line core emitting region is estimated. We find that the velocity width of the neutral FeKα line core falls between that of the broad Balmer emission lines and the corresponding value at the dust reverberation radius for most of the target AGNs. The black hole mass {{M}BH,FeKα } estimated with this method is then compared with other black hole mass estimates, such as the broad emission-line reverberation mass {{M}BH,rev} for type 1 AGNs, the mass {{M}BH,{{H2}O}} based on the H2O maser, and the single-epoch mass estimate {{M}BH,pol} based on the polarized broad Balmer lines for type 2 AGNs. We find that {{M}BH,FeKα } is consistent with {{M}BH,rev} and {{M}BH,pol}, and find that {{M}BH,FeKα } correlates well with {{M}BH,{{H2}O}}. These results suggest that {{M}BH,FeKα } is a potential indicator of the black hole mass for obscured AGNs. In contrast, {{M}BH,FeKα } is systematically larger than {{M}BH,{{H2}O}} by about a factor of 5, and the possible origins are discussed.

Synthesis, docking and ADMET studies of novel chalcone triazoles for anti-cancer and anti-diabetic activity.

PubMed

Chinthala, Yakaiah; Thakur, Sneha; Tirunagari, Shalini; Chinde, Srinivas; Domatti, Anand Kumar; Arigari, Niranjana Kumar; K V N S, Srinivas; Alam, Sarfaraz; Jonnala, Kotesh Kumar; Khan, Feroz; Tiwari, Ashok; Grover, Paramjit

2015-03-26

A series of novel chalcone-triazole derivatives were synthesized and screened for in vitro anticancer activity on the human cancer cell lines IMR32 (neuroblastoma), HepG2 (hepatoma) and MCF-7 (breast adenocarcinoma), DU-145 (prostate carcinoma), and A549 (lung adenocarcinoma). Among the tested compounds, 4r showed the most promising anticancer activity in all the cell lines whereas, compounds 4c (IC50 65.86 μM), 4e (IC50 66.28 μM), 4o (IC50 35.81 μM), 4q (IC50 50.82 μM) and 4s (IC50 48.63 μM) showed better activity than the standard doxorubicin (IC50 69.33 μM) in A549 cell line alone. Rat intestinal α-glucosidase inhibitory activity of the synthesized derivatives showed 4m (IC50 67.77 μM), 4p (IC50 74.94 in μM) and 4s (IC50 102.10 μM) as most active compared to others. The in silico docking of synthesized derivatives 4a-4t with DNA topoisomerase IIα revealed the LibDock score in the range of 71.2623-118.29 whereas, compounds 4h, 4m, 4p and 4s with docking target α-glucosidase were in the range of 100.372-107.784. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

High Resolution X-ray Spectroscopy and Star Formation: HETG Observations of the Pre-Main Sequence Stellar Cluster IC 348

NASA Astrophysics Data System (ADS)

Principe, David; Huenemoerder, David P.; Schulz, Norbert; Kastner, Joel H.; Weintraub, David; Preibisch, Thomas

2018-01-01

We present Chandra High Energy Transmission Grating (HETG) observations of the ∼3 Myr old pre-main sequence (pre-MS) stellar cluster IC 348. With 400-500 cluster members at a distance of ∼300 pc, IC 348 is an ideal target to observe a large number of X-ray sources in a single pointing and is thus an extremely efficient use of Chandra-HETG. High resolution X-ray spectroscopy offers a means to investigate detailed spectral characteristic of X-ray emitting plasmas and their surrounding environments. We present preliminary results where we compare X-ray spectral signatures (e.g., luminosity, temperature, column density, abundance) of the X-ray brightest pre-MS stars in IC 348 with spectral type, multiwavelength signatures of accretion, and the presence of circumstellar disks at multiple stages of pre-MS stellar evolution. Assuming all IC 348 members formed from the same primordial molecular cloud, any disparity between coronal abundances of individual members, as constrained by the identification and strength of emission lines, will constrain the source(s) of coronal chemical evolution at a stage of pre-MS evolution vital to the formation of planets.

Efficient synthesis and evaluation of bis-pyridinium/bis-quinolinium metallosalophens as antibiotic and antitumor candidates

NASA Astrophysics Data System (ADS)

Elshaarawy, Reda F. M.; Eldeen, Ibrahim M.; Hassan, Eman M.

2017-01-01

Inspired with the pharmacological diversity of salophens and in our endeavor to explore a new strategy which may conflict the invasion of drug resistance, we report herein efficient synthetic routes for the synthesis of new RO-salophen(Cl), pyridinium/quinolinium-based salophens (3a-e) and metallosalophens (4a-j). These new architectures have been structurally characterized by elemental and spectral analysis as well pharmacologically evaluated for their in vitro antimicrobial, against a common panel of pathogenic bacterial and fungal strains, and anticancer activities against human colon carcinoma (HCT-116) cell lines. Antimicrobial assay results revealed that all tested compounds exhibited moderate to superb broad-spectrum efficacy in comparison to the standard antibiotic with a preferential ability to perform as a fungicides than to act as bactericides. Noteworthy, VO(II)-salophens are more effective in reduction HCT-116 cell viability than Cu(II)-salophens. For example, VO(II)-salophen3 (4f) (IC50 = 2.13 μg/mL) was ca. 10-fold more efficient than Cu(II)-salophen3 (4e) (IC50 = 20.30 μg/mL).

A Method for Localizing Energy Dissipation in Blazars Using Fermi Variability

NASA Technical Reports Server (NTRS)

Dotson, Amanda; Georganopoulos, Markos; Kazanas, Demosthenes; Perlman, Eric S.

2013-01-01

The distance of the Fermi-detected blazar gamma-ray emission site from the supermassive black hole is a matter of active debate. Here we present a method for testing if the GeV emission of powerful blazars is produced within the sub-pc scale broad line region (BLR) or farther out in the pc-scale molecular torus (MT) environment. If the GeV emission takes place within the BLR, the inverse Compton (IC) scattering of the BLR ultraviolet (UV) seed photons that produces the gamma-rays takes place at the onset of the Klein-Nishina regime. This causes the electron cooling time to become practically energy independent and the variation of the gamma-ray emission to be almost achromatic. If on the other hand the -ray emission is produced farther out in the pc-scale MT, the IC scattering of the infrared (IR) MT seed photons that produces the gamma-rays takes place in the Thomson regime, resulting to energy-dependent electron cooling times, manifested as faster cooling times for higher Fermi energies. We demonstrate these characteristics and discuss the applicability and limitations of our method.

76 FR 64427 - Illinois Central Railroad Company-Discontinuance of Trackage Rights Exemption-in Madison, Yazoo...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-18

... rights from GRYR by virtue of IC's retention of the trackage rights upon its sale of the Grenada Line to... line can be rerouted over other lines; (3) no formal complaint filed by a user of IC's trackage rights....S. District Court or has been decided in favor of complainant within the 2-year period; and (4) the...

Light-induced voltage alteration for integrated circuit analysis

DOEpatents

Cole, Jr., Edward I.; Soden, Jerry M.

1995-01-01

An apparatus and method are described for analyzing an integrated circuit (IC), The invention uses a focused light beam that is scanned over a surface of the IC to generate a light-induced voltage alteration (LIVA) signal for analysis of the IC, The LIVA signal may be used to generate an image of the IC showing the location of any defects in the IC; and it may be further used to image and control the logic states of the IC. The invention has uses for IC failure analysis, for the development of ICs, for production-line inspection of ICs, and for qualification of ICs.

Light-induced voltage alteration for integrated circuit analysis

DOEpatents

Cole, E.I. Jr.; Soden, J.M.

1995-07-04

An apparatus and method are described for analyzing an integrated circuit (IC). The invention uses a focused light beam that is scanned over a surface of the IC to generate a light-induced voltage alteration (LIVA) signal for analysis of the IC. The LIVA signal may be used to generate an image of the IC showing the location of any defects in the IC; and it may be further used to image and control the logic states of the IC. The invention has uses for IC failure analysis, for the development of ICs, for production-line inspection of ICs, and for qualification of ICs. 18 figs.

THE DIFFERENCES IN THE TORUS GEOMETRY BETWEEN HIDDEN AND NON-HIDDEN BROAD LINE ACTIVE GALACTIC NUCLEI

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

Ichikawa, Kohei; Ueda, Yoshihiro; Packham, Christopher

2015-04-20

We present results from the fitting of infrared (IR) spectral energy distributions of 21 active galactic nuclei (AGNs) with clumpy torus models. We compiled high spatial resolution (∼0.3–0.7 arcsec) mid-IR (MIR) N-band spectroscopy, Q-band imaging, and nuclear near- and MIR photometry from the literature. Combining these nuclear near- and MIR observations, far-IR photometry, and clumpy torus models enables us to put constraints on the torus properties and geometry. We divide the sample into three types according to the broad line region (BLR) properties: type-1s, type-2s with scattered or hidden broad line region (HBLR) previously observed, and type-2s without any publishedmore » HBLR signature (NHBLR). Comparing the torus model parameters gives us the first quantitative torus geometrical view for each subgroup. We find that NHBLR AGNs have smaller torus opening angles and larger covering factors than HBLR AGNs. This suggests that the chance to observe scattered (polarized) flux from the BLR in NHBLR could be reduced by the dual effects of (a) less scattering medium due to the reduced scattering volume given the small torus opening angle and (b) the increased torus obscuration between the observer and the scattering region. These effects give a reasonable explanation for the lack of observed HBLR in some type-2 AGNs.« less

Late-time spectroscopy of envelope-stripped SNe: Figuring the central engine

NASA Astrophysics Data System (ADS)

Kawabata, Koji

2011-01-01

We propose to perform late-time spectroscopy of envelope-stripped core-collapse supernovae (SNe), i.e., Type Ib/c/IIb SNe. We aim to examine the explosion physics and its dependence on the progenitor mass. The key information is the asphericity and the chemical composition of the inner atmosphere, which can be explored by late-time observations. The difference in [O I] line profiles indicates that GRB-associated energetic SNe Ic (like SN 1998bw) and non-GRB energetic SNe Ic (2003jd) are intrinsically similar aspherical explosions that are differently viewed (pole-on for 1998bw and nearly edge-on for 2003jd). Our continuing study suggests that the asphericity is rather common characteristic even for normal energy SNe without a GRB. However, it is still unclear how the intermediate types of SNe (SNe Ib/IIb) are produced and how they connected with other types of core-collapse SNe. High-quality late-time spectra of SNe Ib/Ic/IIb are still lacking. We propose to obtain a larger number of nebular spectra of envelope-stripped SNe so that we examine the degree of the asphericity as a function of the progenitor's mass, explosion energy, amount of synthesized ^56Ni, and the physical properties of the central remnant.

Late-time spectroscopy of envelope-stripped SNe: Figuring the central engine

NASA Astrophysics Data System (ADS)

Kawabata, Koji

2012-01-01

We propose to perform late-time spectroscopy of envelope-stripped core-collapse supernovae (SNe), i.e., Type Ib/c/IIb SNe. We aim to examine the explosion physics and its dependence on the progenitor mass. The key information is the asphericity and the chemical composition of the inner atmosphere, which can be explored by late-time observations. The difference in [O I] line profiles indicates that GRB-associated energetic SNe Ic (like SN 1998bw) and non-GRB energetic SNe Ic (2003jd) are intrinsically similar aspherical explosions that are differently viewed (pole-on for 1998bw and nearly edge-on for 2003jd). Our continuing study suggests that the asphericity is rather common characteristic even for normal energy SNe without a GRB. However, it is still unclear how the intermediate types of SNe (SNe Ib/IIb) are produced and how they connected with other types of core-collapse SNe. High-quality late-time spectra of SNe Ib/Ic/IIb are still lacking. We propose to obtain a larger number of nebular spectra of envelope-stripped SNe including SNe IIb so that we examine the degree of the asphericity explosion energy, amount of synthesized ^56Ni and the physical properties of the central remnant as a function of the progenitor's mass.

Observational and theoretical spectra of supernovae

NASA Astrophysics Data System (ADS)

Wheeler, J. Craig; Swartz, Douglas A.; Harkness, Robert P.

1993-05-01

Progress in nuclear astrophysics by means of quantitative supernova spectroscopy is discussed with special concentration on type Ia, Ib and Ic and on SN 1987A. Spectral calculations continue to support an exploding C/O white dwarf as the best model of a SN Ia. Deflagration model W7 produces good maximum light spectra of SN Ia and seems to have a better composition distribution compared to delayed detonation models, but proper treatment of opacity remains a problem and the physical basis of SN Ia explosions is still not completely understood. All models for SN Ia predict large quantities of 56Co in the ejecta, but it is not clear that observations confirm this. Although the evolutionary origin of SN Ia remains uncertain, there is recent evidence that transfer of hydrogen in a binary system may be involved, as long suspected. There has been progress in comparing dynamical models with the optical/IR spectra of SN 1987A. The evolution of the [OI] λλ6300, 6364 feature and the presence of strong persistent HeI λ10 830 indicate that both the envelope and core material contribute substantially to the formation of emission lines in the nebular phase and that neither the core nor the envelope can be neglected. Blending with nearby hydrogen lines may affect both of these spectral features, thereby complicating the analysis of the lines. The effects of continuum transfer and photoionization have been included and are under study. The discrepancies between theoretical and observed spectra are due primarily to the one-dimensional hydrodynamic models. The spectral data are not consistent with the high density ``spike'' (in radial coordinate) of the core material that is predicted by all such models. Analysis of the light curves of SN Ib and SN Ic supernovae implies that there are significant differences in their physical properties. Some SN Ib have considerably more ejecta mass than SN Ic events. SN Ib require He-rich atmospheres to produce the observed strong optical lines of HeI somewhat after maximum. SN Ic events require a considerable depletion, if not absence, of helium. Calculations of the nebular phase after about 200 days show that the optical spectra of SN Ib/c will not reveal HeI even if helium is present. The spectra at that phase are rather insensitive to variations in the mass and composition. The similarity of the optical spectra of SN Ib and Ic events at late times thus does not mean that they are physically very similar. Observations of the HeI λ10 830 line could provide a good diagnostic of the atmospheric composition of Sn Ib and SN Ic.

Observational and theoretical spectra of supernovae

NASA Astrophysics Data System (ADS)

Craig Wheeler, J.; Swartz, Douglas A.; Harkness, Robert P.

1993-05-01

Progress in nuclear astrophysics by means of quantitative supernova spectroscopy is discussed with special concentration on type Ia, Ib and Ic and on SN 1987A. Spectral calculations continue to support an exploding C/O white dwarf as the best model of a SN Ia. Deflagration model W7 produces good maximum light spectra of SN Ia and seems to have a better composition distribution compared to delayed detonation models, but proper treatment of opacity remains a problem and the physical basis of SN Ia explosions is still not completely understood. All models for SN Ia predict large quantities of 56Co in the ejecta, but it is not clear that observations confirm this. Although the evolutionary origin of SN Ia remains uncertain, there is recent evidence that transfer of hydrogen in a binary system may be involved, as long suspected. There has been progress in comparing dynamical models with the optical/IR spectra of SN 1987A. The evolution of the [OI] λλ6300, 6364 feature and the presence of strong persistent HeI λ10 830 indicate that both the envelope and core material contribute substantially to the formation of emission lines in the nebular phase and that neither the core nor the envelope can be neglected. Blending with nearby hydrogen lines may affect both of these spectral features, thereby complicating the analysis of the lines. The effects of continuum transfer and photoionization have been included and are under study. The discrepancies between theoretical and observed spectra are due primarily to the one-dimensional hydrodynamic models. The spectral data are not consistent with the high density “spike” (in radial coordinate) of the core material that is predicted by all such models. Analysis of the light curves of SN Ib and SN Ic supernovae implies that there are significant differences in their physical properties. Some SN Ib have considerably more ejecta mass than SN Ic events. SN Ib require He-rich atmospheres to produce the observed strong optical lines of HeI somewhat after maximum. SN Ic events require a considerable depletion, if not absence, of helium. Calculations of the nebular phase after about 200 days show that the optical spectra of SN Ib/c will not reveal HeI even if helium is present. The spectra at that phase are rather insensitive to variations in the mass and composition. The similarity of the optical spectra of SN Ib and Ic events at late times thus does not mean that they are physically very similar. Observations of the HeI λ10 830 line could provide a good diagnostic of the atmospheric composition of Sn Ib and SN Ic.

Trees Containing Built-In Pulping Catalysts - Final Report - 08/18/1997 - 08/18/2000

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

Pullman, G.; Dimmel, D.; Peter, G.

2000-08-18

Several hardwood and softwood trees were analyzed for the presence of anthraquinone-type molecules. Low levels of anthraquinone (AQ) and anthrone components were detected using gas chromatography-mass spectroscopy and sensitive selected-ion monitoring techniques. Ten out of seventeen hardwood samples examined contained AQ-type components; however, the levels were typically below {approximately}6 ppm. No AQs were observed in the few softwood samples that were examined. The AQs were more concentrated in the heartwood of teak than in the sapwood. The delignification of pine was enhanced by the addition of teak chips ({approximately}0.7% AQ-equivalence content) to the cook, suggesting that endogenous AQs can bemore » released from wood during pulping and can catalyze delignification reactions. Eastern cottonwood contained AQ, methyl AQ, and dimethyl AQ, all useful for wood pulping. This is the first time unsubstituted AQ has been observed in wood extracts. Due to the presence of these pulping catalysts, rapid growth rates in plantation settings, and the ease of genetic transformation, eastern cottonwood is a suitable candidate for genetic engineering studies to enhance AQ content. To achieve effective catalytic pulping activity, poplar and cottonwood, respectively, require {approximately}100 and 1000 times more for pulping catalysts. A strategy to increase AQ concentration in natural wood was developed and is currently being tested. This strategy involves ''turning up'' isochorismate synthase (ICS) through genetic engineering. Isochorismate synthase is the first enzyme in the AQ pathway branching from the shikimic acid pathway. In general, the level of enzyme activity at the first branch point or committed step controls the flux through a biosynthetic pathway. To test if the level of ICS regulates AQ biosynthesis in plant tissues, we proposed to over-express this synthase in plant cells. A partial cDNA encoding a putative ICS was available from the random cDNA sequencing project carried out with Arabidopsis thaliana. We used this putative plant ICS gene fragment to isolate and sequence a full-length ICS cDNA from Arabidopsis thaliana. The putative full-length cDNA encodes for a 569 amino acid protein of {approximately}62kDa. This sequence represents the first full-length ICS cDNA isolated from a plant. When inserted into E. coli, our isolated cDNA over-expressed ICS protein in the insoluble inclusion bodies. A plant expression vector containing the ICS cDNA, NP II for selection on the antibiotic kanamycin, and duplicated 35S-cauliflower mosaic virus promoter were inserted into Agrobacterium tumefaciens strain GV3101. Transformation experiments for insertion of these foreign genes into Populus deltoides 'C175' resulted in eight lines able to regenerate shoots and grow roots in the presence of kanamycin. Plants from these eight lines have acclimated to growth in sterile soil and will be moved to a greenhouse environment in spring 2001. Non rooted shoots from each line are currently being multiplied by shoot culture. When enough shoot tissue and/or greenhouse plant stem tissue is available, AQ analysis will be done and compared with non transformed control tissue.« less

Synthesis, in vitro and in vivo giardicidal activity of nitrothiazole-NSAID chimeras displaying broad antiprotozoal spectrum.

PubMed

Colín-Lozano, Blanca; León-Rivera, Ismael; Chan-Bacab, Manuel Jesús; Ortega-Morales, Benjamín Otto; Moo-Puc, Rosa; López-Guerrero, Vanessa; Hernández-Núñez, Emanuel; Argüello-Garcia, Raúl; Scior, Thomas; Barbosa-Cabrera, Elizabeth; Navarrete-Vázquez, Gabriel

2017-08-01

We designed and synthesized five new 5-nitrothiazole-NSAID chimeras as analogues of nitazoxanide, using a DCC-activated amidation. Compounds 1-5 were tested in vitro against a panel of five protozoa: 2 amitochondriates (Giardia intestinalis, Trichomonas vaginalis) and 3 kinetoplastids (Leishmania mexicana, Leishmania amazonensis and Trypanosoma cruzi). All chimeras showed broad spectrum and potent antiprotozoal activities, with IC 50 values ranging from the low micromolar to nanomolar order. Compounds 1-5 were even more active than metronidazole and nitazoxanide, two marketed first-line drugs against giardiasis. In particular, compound 4 (an indomethacin hybrid) was one of the most potent of the series, inhibiting G. intestinalis growth in vitro with an IC 50 of 0.145μM. Compound 4 was 38-times more potent than metronidazole and 8-times more active than nitazoxanide. The in vivo giardicidal effect of 4 was evaluated in a CD-1 mouse model obtaining a median effective dose of 1.709μg/kg (3.53nmol/kg), a 321-fold and 1015-fold increase in effectiveness after intragastric administration over metronidazole and nitazoxanide, respectively. Compounds 1 and 3 (hybrids of ibuprofen and clofibric acid), showed potent giardicidal activities in the in vitro as well as in the in vivo assays after oral administration. Therefore, compounds 1-5 constitute promising drug candidates for further testing in experimental chemotherapy against giardiasis, trichomoniasis, leishmaniasis and even trypanosomiasis infections. Copyright © 2017 Elsevier Ltd. All rights reserved.

LINE IDENTIFICATIONS OF TYPE I SUPERNOVAE: ON THE DETECTION OF Si II FOR THESE HYDROGEN-POOR EVENTS

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

Parrent, J. T.; Milisavljevic, D.; Soderberg, A. M.

2016-03-20

Here we revisit line identifications of type I supernovae (SNe I) and highlight trace amounts of unburned hydrogen as an important free parameter for the composition of the progenitor. Most one-dimensional stripped-envelope models of supernovae indicate that observed features near 6000–6400 Å in type I spectra are due to more than Si ii λ6355. However, while an interpretation of conspicuous Si ii λ6355 can approximate 6150 Å absorption features for all SNe Ia during the first month of free expansion, similar identifications applied to 6250 Å features of SNe Ib and Ic have not been as successful. When the corresponding synthetic spectra aremore » compared with high-quality timeseries observations, the computed spectra are frequently too blue in wavelength. Some improvement can be achieved with Fe ii lines that contribute redward of 6150 Å; however, the computed spectra either remain too blue or the spectrum only reaches a fair agreement when the rise-time to peak brightness of the model conflicts with observations by a factor of two. This degree of disagreement brings into question the proposed explosion scenario. Similarly, a detection of strong Si ii λ6355 in the spectra of broadlined Ic and super-luminous events of type I/R is less convincing despite numerous model spectra used to show otherwise. Alternatively, we suggest 6000–6400 Å features are possibly influenced by either trace amounts of hydrogen or blueshifted absorption and emission in Hα, the latter being an effect which is frequently observed in the spectra of hydrogen-rich, SNe II.« less

The first total synthesis and biological evaluation of marine natural products ma'edamines A and B.

PubMed

Saha, Sanjay; Venkata Ramana Reddy, Ch; Chiranjeevi, T; Addepally, Uma; Chinta Rao, T S; Patro, Balaram

2013-02-15

We have developed the first total syntheses of marine natural products ma'edamines A (18) and B (20). Structurally, they contain a pyrazine-2-(1H)-one core and were screened for antiproliferative activity on several cancer cell lines. Out of the six cell lines tested, ma'edamines A and B showed significant cytotoxicity against human colon cancer line COLO 205 (IC(50) 7.9 and 10.3 μM, respectively), breast cancer cell line MCF-7 (IC(50): 6.9 and 10.5 μM, respectively) and human lung adenocarcinoma cell line A549 (IC(50): 12.2 and 15.4 μM, respectively). The apoptotic effect of ma'edamines was confirmed by comet assay. Hence ma'edamines are likely to be useful as leads for development of a new class of anti-cancer agents. Copyright © 2012 Elsevier Ltd. All rights reserved.

Development of a Specific Monoclonal Antibody for the Quantification of Artemisinin in Artemisia annua and Rat Serum.

PubMed

Guo, Suqin; Cui, Yongliang; Wang, Kunbi; Zhang, Wei; Tan, Guiyu; Wang, Baomin; Cui, Liwang

2016-03-01

Artemisinin, extracted from Artemisia annua, and its derivatives are important frontline antimalarials. To produce specific antibodies for the detection and quantification of artemisinin, artemisinin was transformed to 9-hydroxyartemisinin by microbial fermentation, which was used to prepare a 9-succinate artemisinin hapten for conjugation with ovalbumin. A monoclonal antibody (mAb), designated as 3H7A10, was selected from hybridoma cell lines which showed high specificity to artemisinin. No competitive inhibition was observed with artesunate, dihydroartemisinin, and artemether for up to 20,000 ng mL(-1). An indirect competitive enzyme-linked immunosorbent assay (icELISA) was developed, which showed a concentration causing 50% of inhibition (IC50) for artemisinin as 2.6 ng mL(-1) and a working range of 0.6-11.5 ng mL(-1). The icELISA was applied for the quantification of artemisinin in crude extracts of wild A. annua and the study of pharmacokinetics of artemisinin in rat serum after intraperitoneal injection. The results were highly correlated with those determined by HPLC-UV analysis (R(2) = 0.9919). In comparison with reported antiartemisinin mAbs which have broad cross-reactivity with other artemisinin derivatives, the high specificity of 3H7A10 for artemisinin will enable development of methods for quantification of artemisinin in Artemisia plants and antimalarial drugs such as Arco and for pharmacokinetic studies.

International Continence Society supported pelvic physiotherapy education guideline.

PubMed

Bakker, Els; Shelly, Beth; Esch, Fetske H; Frawley, Helena; McClurg, Doreen; Meyers, Peter

2018-02-01

To provide a guideline of desired knowledge, clinical skills and education levels in Pelvic Physiotherapy (PT). Physiotherapy (PT) involves "using knowledge and skills unique to physiotherapists" and, "is the service only provided by, or under the direction and supervision of a physiotherapist." 1 METHODS: The PT Committee, within the body of the International Continence Society (ICS), collected information regarding existing educational levels for pelvic floor PT. Through face to face and on on-line discussion consensus was reached which was summarized in three progressive educational levels based on knowledge and skills and brought together in a guideline. The guideline was submitted to all physiotherapists and the Educational Committee of the ICS, and after approval, submitted to the Executive Board of the ICS. The guideline lists, in a progressive way, knowledge areas and skills to be achieved by education. It is broad and allows for individual interpretation based on local situations regarding education and healthcare possibilities. It is intended to be dynamic and updated on a regular basis. The proposed Pelvic PT education guideline is a dynamic document that allows course creators to plan topics for continuing course work and to recognize educational level of a therapist in the field of Pelvic PT. This education guideline can be used to set minimum worldwide standards resulting in higher skill levels for local pelvic physiotherapists and thereby better patient care outcome. © 2018 Wiley Periodicals, Inc.

Inhibitory activity on type 2 diabetes and hypertension key-enzymes, and antioxidant capacity of Veronica persica phenolic-rich extracts.

PubMed

Sharifi-Rad, M; Tayeboon, G S; Sharifi-Rad, J; Iriti, M; Varoni, E M; Razazi, S

2016-05-30

Veronica genus (Plantaginaceae) is broadly distributed in different habitats. In this study, the inhibitory activity of free soluble and conjugated phenolic extracts of Veronica persica on key enzymes associated to type 2 diabetes (α-glucosidase and α-amylase) and hypertension (angiotensin I converting enzyme, ACE) was assessed, as well as their antioxidant power. Our results showed that both the extracts inhibited α-amylase, α-glucosidase and ACE in a dose-dependent manner. In particular, free phenolic extract significantly (P<0.05) inhibited α-glucosidase (IC50 532.97 µg/mL), whereas conjugated phenolic extract significantly (P<0.05) inhibited α-amylase (IC50 489.73 µg/mL) and ACE (290.06 µg/mL). The enzyme inhibitory activities of the extracts were not associated with their phenolic content. Anyway, the inhibition of α-amylase, α-glucosidase and ACE, along with the antioxidant capacity of the phenolic-rich extracts, could represent a putative mechanism through which V. persica exerts its antidiabetes and antihypertension effects.

Ionized and Molecular Gas in IC 860: Evidence for an Outflow

NASA Astrophysics Data System (ADS)

Adams, Carson; Alatalo, Katherine; Medling, Anne M.

2018-01-01

Galaxies at present-day fall predominantly in two distinct populations, as either blue, star-forming spirals or red, quiescent early-type galaxies. Blue galaxies appear to evolve onto the red sequence as star formation is quenched. The absence of a significant population falling in the intermediate ‘green valley’ implies that these transitions must occur rapidly. Identifying the initial properties of and pathways taken by these ‘dying galaxies’ is essential to building a complete understanding of galactic evolution. In this work, we investigate these phenomena in action within IC860 — a nearby, early-type spiral in the initial stages of undergoing a rapid transition in the presence of a powerful AGN-driven molecular outflow. As a shocked, post-starburst galaxy with an intermediate-age stellar population which lies on the blue end of the green valley, IC860 provides a window into the early stages of galaxy transition and AGN feedback. We present Hubble Space Telescope imaging of IC860 showing a violent, dusty outflow originating from a compact core. We find that the mean velocity map of the CO(1-0) from CARMA suggests a dynamically excited bar funneling molecular gas into the galactic center. Finally, we present kinematic maps of ionized gas emission lines as well as sodium D absorption tracing neutral winds obtained by the Wide-Field Spectrograph.

PTP1B inhibitory and cytotoxic C-24 epimers of Δ28-24-hydroxy stigmastane-type steroids from the brown alga Dictyopteris undulata Holmes.

PubMed

Feng, Mei-Tang; Wang, Ting; Liu, Ai-Hong; Li, Jia; Yao, Li-Gong; Wang, Bin; Guo, Yue-Wei; Mao, Shui-Chun

2018-02-01

Ten stigmastane-type steroids bearing unusual Δ 28 -24-hydroxy side chains, dictyopterisins A-J, including three pairs of C-24 epimers, dictyopterisins B/C, F/G, and I/J, were isolated from the brown alga Dictyopteris undulata Holmes, together with two previously reported analogues, (24S)- and (24R)-saringosterol. Their structures were elucidated on the basis of extensive spectroscopic analysis, with their absolute configurations at the stereogenic center C-24 of the side chain being assigned by a direct comparison of 1 H NMR data with those of related known compounds. The absolute configurations of the steroidal nuclei of dictyopterisins A, B, and H were determined using the modified Mosher's method. The mixture of dictyopterisins D and E and dictyopterisin I exhibited promising PTP1B inhibitory activities with IC 50 values of 1.88 and 3.47 μM, respectively, comparable to the positive control oleanolic acid (IC 50 , 2.78 μM). In addition, the mixture of dictyopterisins D and E and dictyopterisins F-J displayed significant cytotoxicities against the human cancer cell lines HL-60 (IC 50 from 1.02 to 2.70 μM) and A-549 (IC 50 from 1.35 to 2.85 μM). Copyright © 2017 Elsevier Ltd. All rights reserved.

An Asymmetric Hypernova (SN 2003jd) Viewed Off-Axis, and a Link to Gamma-Ray Bursts

NASA Astrophysics Data System (ADS)

Maeda, K.; et al.

2006-02-01

Authors: Keiichi Maeda, Ken Nomoto, Nozomu Tominaga (Tokyo), Paolo Mazzali, Elena Pian (Trieste), Jinsong Deng (Beijing) Type Ic supernovae, the explosions following the core collapse ofmassive stars that have previously lost their hydrogen and heliumenvelopes, are particularly interesting because of the link withlong-duration gamma-ray bursts. Although indications exist that theseexplosions are aspherical, direct evidence has still been missing.Late-time observations of SN 2003jd, a luminous hypernova, providesuch evidence. Recent Subaru and Keck spectra reveal double-peakedprofiles in the nebular lines of neutral oxygen and magnesium. Theseprofiles are different from those of known Type Ic supernovae, with orwithout a gamma-ray burst, and they can be understood if SN 2003jd wasan aspherical, axisymmetric explosion viewed from near the equatorialplane. If SN 2003jd was associated with a gamma-ray burst, we missedthe burst as it was pointing away from us.

SPIRITS 15c and SPIRITS 14buu: Two Obscured Supernovae in the Nearby Star-forming Galaxy IC 2163

NASA Astrophysics Data System (ADS)

Jencson, Jacob E.; Kasliwal, Mansi M.; Johansson, Joel; Contreras, Carlos; Castellón, Sergio; Bond, Howard E.; Monson, Andrew J.; Masci, Frank J.; Cody, Ann Marie; Andrews, Jennifer E.; Bally, John; Cao, Yi; Fox, Ori D.; Gburek, Timothy; Gehrz, Robert D.; Green, Wayne; Helou, George; Hsiao, Eric; Morrell, Nidia; Phillips, Mark; Prince, Thomas A.; Simcoe, Robert A.; Smith, Nathan; Tinyanont, Samaporn; Williams, Robert

2017-03-01

SPitzer InfraRed Intensive Transients Survey—SPIRITS—is an ongoing survey of nearby galaxies searching for infrared (IR) transients with Spitzer/IRAC. We present the discovery and follow-up observations of one of our most luminous (M [4.5] = -17.1 ± 0.4 mag, Vega) and reddest ([3.6] - [4.5] = 3.0 ± 0.2 mag) transients, SPIRITS 15c. The transient was detected in a dusty spiral arm of IC 2163 (D ≈ 35.5 Mpc). Pre-discovery ground-based imaging revealed an associated, shorter-duration transient in the optical and near-IR (NIR). NIR spectroscopy showed a broad (≈8400 km s-1), double-peaked emission line of He I at 1.083 μm, indicating an explosive origin. The NIR spectrum of SPIRITS 15c is similar to that of the Type IIb SN 2011dh at a phase of ≈200 days. Assuming an A V = 2.2 mag of extinction in SPIRITS 15c provides a good match between their optical light curves. The NIR light curves, however, show some minor discrepancies when compared with SN 2011dh, and the extreme [3.6]-[4.5] color has not been previously observed for any SN IIb. Another luminous (M 4.5 = -16.1 ± 0.4 mag) event, SPIRITS 14buu, was serendipitously discovered in the same galaxy. The source displays an optical plateau lasting ≳80 days, and we suggest a scenario similar to the low-luminosity Type IIP SN 2005cs obscured by A V ≈ 1.5 mag. Other classes of IR-luminous transients can likely be ruled out in both cases. If both events are indeed SNe, this may suggest that ≳18% of nearby core-collapse SNe are missed by currently operating optical surveys.

TDR method for determine IC's parameters

NASA Astrophysics Data System (ADS)

Timoshenkov, V.; Rodionov, D.; Khlybov, A.

2016-12-01

Frequency domain simulation is a widely used approach for determine integrated circuits parameters. This approach can be found in most of software tools used in IC industry. Time domain simulation approach shows intensive usage last years due to some advantages. In particular it applicable for analysis of nonlinear and nonstationary systems where frequency domain is inapplicable. Resolution of time domain systems allow see heterogeneities on distance 1mm, determine it parameters and properties. Authors used approach based on detecting reflected signals from heterogeneities - time domain reflectometry (TDR). Field effect transistor technology scaling up to 30-60nm gate length and 10nm gate dielectric, heterojunction bi-polar transistors with 10-30nm base width allows fabricate digital IC's with 20GHz clock frequency and RF-IC's with tens GHz bandwidth. Such devices and operation speed suppose transit signal by use microwave lines. There are local heterogeneities can be found inside of the signal path due to connections between different parts of signal lines (stripe line-RF-connector pin, stripe line - IC package pin). These heterogeneities distort signals that cause bandwidth decrease for RF-devices. Time domain research methods of transmission and reflected signals give the opportunities to determine heterogeneities, it properties, parameters and built up equivalent circuits. Experimental results are provided and show possibility for inductance and capacitance measurement up to 25GHz. Measurements contains result of signal path research on IC and printed circuit board (PCB) used for 12GHz RF chips. Also dielectric constant versus frequency was measured up to 35GHz.

Novel, broad-spectrum anticonvulsants containing a sulfamide group: advancement of N-((benzo[b]thien-3-yl)methyl)sulfamide (JNJ-26990990) into human clinical studies.

PubMed

Parker, Michael H; Smith-Swintosky, Virginia L; McComsey, David F; Huang, Yifang; Brenneman, Douglas; Klein, Brian; Malatynska, Ewa; White, H Steve; Milewski, Michael E; Herb, Mark; Finley, Michael F A; Liu, Yi; Lubin, Mary Lou; Qin, Ning; Iannucci, Robert; Leclercq, Laurent; Cuyckens, Filip; Reitz, Allen B; Maryanoff, Bruce E

2009-12-10

In seeking broad-spectrum anticonvulsants to treat epilepsy and other neurological disorders, we synthesized and tested a group of sulfamide derivatives (4a-k, 5), which led to the clinical development of 4a (JNJ-26990990). This compound exhibited excellent anticonvulsant activity in rodents against audiogenic, electrically induced, and chemically induced seizures, with very weak inhibition of human carbonic anhydrase-II (IC(50) = 110 microM). The pharmacological profile for 4a supports its potential in the treatment of multiple forms of epilepsy, including pharmacoresistant variants. Mechanistically, 4a inhibited voltage-gated Na(+) channels and N-type Ca(2+) channels but was not effective as a K(+) channel opener. The pharmacokinetics and metabolic properties of 4a are discussed.

Electron scattering wings on lines in interacting supernovae

NASA Astrophysics Data System (ADS)

Huang, Chenliang; Chevalier, Roger A.

2018-03-01

We consider the effect of electron scattering on lines emitted as a result of supernova interaction with a circumstellar medium, assuming that the scattering occurs in ionized gas in the pre-shock circumstellar medium. The single scattering case gives the broad component in the limit of low optical depth, showing a velocity full width half-maximum that is close to the thermal velocities of electrons. The line shape is approximately exponential at low velocities and steepens at higher velocities. At higher optical depths, the line profile remains exponential at low velocities, but wings strengthen with increasing optical depth. In addition to the line width, the ratio of narrow to broad (scattered) line strength is a possible diagnostic of the gas. The results depend on the density profile of the circumstellar gas, especially if the scattering and photon creation occur in different regions. We apply the scattering model to a number of supernovae, including Type IIn and Type Ia-circumstellar medium (CSM) events. The asymmetry to the red found in some cases can be explained by scattering in a fast wind region that is indicated by observations.

The Low-Cost Compound Lignosulfonic Acid (LA) Exhibits Broad-Spectrum Anti-HIV and Anti-HSV Activity and Has Potential for Microbicidal Applications

PubMed Central

D’huys, Thomas; Petrova, Mariya I.; Lebeer, Sarah; Snoeck, Robert; Andrei, Graciela; Schols, Dominique

2015-01-01

Objectives Lignosulfonic acid (LA), a low-cost lignin-derived polyanionic macromolecule, was extensively studied for its anti-HIV and anti-HSV activity in various cellular assays, its mechanism of viral inhibition and safety profile as potential microbicide. Results LA demonstrated potent inhibitory activity of HIV replication against a wide range of R5 and X4 HIV strains and prevented the uptake of HIV by bystander CD4+ T cells from persistently infected T cells in vitro (IC50: 0.07 – 0.34 μM). LA also inhibited HSV-2 replication in vitro in different cell types (IC50: 0.42 – 1.1 μM) and in rodents in vivo. Furthermore, LA neutralized the HIV-1 and HSV-2 DC-SIGN-mediated viral transfer to CD4+ T cells (IC50: ∼1 μM). In addition, dual HIV-1/HSV-2 infection in T cells was potently blocked by LA (IC50: 0.71 μM). No antiviral activity was observed against the non-enveloped viruses Coxsackie type B4 and Reovirus type 1. LA is defined as a HIV entry inhibitor since it interfered with gp120 binding to the cell surface of T cells. Pretreatment of PBMCs with LA neither increased expression levels of cellular activation markers (CD69, CD25 and HLA-DR), nor enhanced HIV-1 replication. Furthermore, we found that LA had non-antagonistic effects with acyclovir, PRO2000 or LabyA1 (combination index (CI): 0.46 – 1.03) in its anti-HSV-2 activity and synergized with tenofovir (CI: 0.59) in its anti-HIV-1 activity. To identify mechanisms of LA resistance, we generated in vitro a mutant HIV-1 NL4.3LAresistant virus, which acquired seven mutations in the HIV-1 envelope glycoproteins: S160N, V170N, Q280H and R389T in gp120 and K77Q, N113D and H132Y in gp41. Additionally, HIV-1 NL4.3LAresistant virus showed cross-resistance with feglymycin, enfuvirtide, PRO2000 and mAb b12, four well-described HIV binding/fusion inhibitors. Importantly, LA did not affect the growth of vaginal Lactobacilli strains. Conclusion Overall, these data highlight LA as a potential and unique low-cost microbicide displaying broad anti-HIV and anti-HSV activity. PMID:26132818

In-line interferometer for broadband near-field scanning optical spectroscopy.

PubMed

Brauer, Jens; Zhan, Jinxin; Chimeh, Abbas; Korte, Anke; Lienau, Christoph; Gross, Petra

2017-06-26

We present and investigate a novel approach towards broad-bandwidth near-field scanning optical spectroscopy based on an in-line interferometer for homodyne mixing of the near field and a reference field. In scattering-type scanning near-field optical spectroscopy, the near-field signal is usually obscured by a large amount of unwanted background scattering from the probe shaft and the sample. Here we increase the light reflected from the sample by a semi-transparent gold layer and use it as a broad-bandwidth, phase-stable reference field to amplify the near-field signal in the visible and near-infrared spectral range. We experimentally demonstrate that this efficiently suppresses the unwanted background signal in monochromatic near-field measurements. For rapid acquisition of complete broad-bandwidth spectra we employ a monochromator and a fast line camera. Using this fast acquisition of spectra and the in-line interferometer we demonstrate the measurement of pure near-field spectra. The experimental observations are quantitatively explained by analytical expressions for the measured optical signals, based on Fourier decomposition of background and near field. The theoretical model and in-line interferometer together form an important step towards broad-bandwidth near-field scanning optical spectroscopy.

FE K EMISSION AND ABSORPTION FEATURES IN THE XMM-EPIC SPECTRUM OF THE SEYFERT GALAXY IC 4329A

NASA Technical Reports Server (NTRS)

Markowitz, A.; Reeves, J. N.; Braito, V.

2001-01-01

We present a re-analysis of the XMM-Newton long-look of the X-ray bright Seyfert galaxy IC 4329a. The Fe K bandpass is dominated by two peaks, consistent with emission from neutral or near-neutral Fe Ka and KP. A relativistic diskline model whereby both peaks are the result of one doubly-peaked diskline profile is found to be a poor description of the data. Models using two relativistic disklines are found to describe the emission profile well. A low-inclination, moderately-relativistic dual-diskline model is possible if the contribution from narrow components, due to distant material, is small or absent. A high-inclination, moderately relativistic profile for each peak is possible if there are roughly equal contributions from both the broad and narrow components. Upper limits on Fe XXV and Fe XXVI emission and absorption at the systemic velocity of IC 4329a are obtained. We also present the results of RXTE monitoring of this source obtained so far; the combined XMM-Newton and RXTE data sets allow us to explore the time-resolved spectral behavior of this source on time scales ranging from hours to 2 years. We find no strong evidence for variability of the Fe Ka emission line on any time scale probed, likely due to the minimal level of continuum variability. We detect a narrow absorption line, at a energy of 7.68 keV in the rest frame of the source; its significance has been confirmed using Monte Carlo simulations. This feature is most likely due to absorption from Fe XXVI blueshifted to approximately 0.1c relative to the systemic velocity, making IC 4329a the lowest-redshift AGN known with a high-velocity, highly-ionized outflow component. As is often the case with similar outflows seen in high-luminosity quasars, the estimated mass outflow rate is larger than the inflow accretion rate, signaling that the outflow represents a substantial portion of the total energy budget of the AGN. The outflow could arise from a radiatively-driven disk wind, or it may be in the form of a discrete, transient blob of ejected material.

A spectroscopic search for colliding stellar winds in O-type close binary systems. III - 29 UW Canis Majoris

NASA Technical Reports Server (NTRS)

Wiggs, Michael S.; Gies, Douglas R.

1993-01-01

The orbital-phase variations in the optical emission lines and UV P Cygni lines of the massive O-type binary 29 UW Canis Majoris are investigated in a search for evidence of colliding winds. High SNR spectra of the H-alpha and He I 6678-A emission lines are presented, and radial velocity curves for several features associated with the photosphere of the more luminous primary star are given. The H-alpha features consists of a P Cygni component that shares the motion of the primary, and which probably originates at the base of its wind, and a broad, stationary emission component. It is proposed that the broad emission forms in a plane midway between the stars where the winds collide. A simple geometric model is used to show that this placement of the broad component can explain the lack of orbital velocity shifts, the near-constancy of the emission strength throughout the orbit, the large velocities associated with the H-alpha wings, and the constancy of the velocity range observed.

High Add Valued Application of Turpentine in Crop Production through Structural Modification and QSAR Analysis.

PubMed

Gao, Yanqing; Li, Jingjing; Li, Jian; Song, Zhanqian; Shang, Shibin; Rao, Xiaoping

2018-02-08

Turpentine is a volatile component of resin, which is an abundant forest resource in Southern China. As one of the most important components, the integrated application of β-pinene has been studied. The broad-spectrum evaluation of β-pinene and its analogues has, therefore, been necessary. In an attempt to expand the scope of agro-activity trials, the preparation and the evaluation of the herbicidal activity of a series of β-pinene analogues against three agricultural herbs were carried out. In accordance with the overall herbicidal activity, it is noteworthy that compounds 6k , 6l , and 6m demonstrated extreme activity with IC 50 values of 0.065, 0.065, and 0.052 mol active ingredients/hectare against E. crus-galli . The preliminary structure-activity relationship (SAR) was analyzed and the compounds with the appropriate volatility and substituent type that had beneficial herbicidal activity were analyzed. Simultaneously, the quantitative structure-activity relationship (QSAR) model was built and the most important structural features were indicated, which was, to a certain extent, in line with the SAR study. The study aimed to study the application of the forest resource turpentine in agriculture as a potential and alternative approach for comprehensive utilization.

Development of voice navigation system for the visually impaired by using IC tags.

PubMed

Takatori, Norihiko; Nojima, Kengo; Matsumoto, Masashi; Yanashima, Kenji; Magatani, Kazushige

2006-01-01

There are about 300,000 visually impaired persons in Japan. Most of them are old persons and, cannot become skillful in using a white cane, even if they make effort to learn how to use a white cane. Therefore, some guiding system that supports the independent activities of the visually impaired are required. In this paper, we will describe about a developed white cane system that supports the independent walking of the visually impaired in the indoor space. This system is composed of colored navigation lines that include IC tags and an intelligent white cane that has a navigation computer. In our system colored navigation lines that are put on the floor of the target space from the start point to the destination and IC tags that are set at the landmark point are used for indication of the route to the destination. The white cane has a color sensor, an IC tag transceiver and a computer system that includes a voice processor. This white cane senses the navigation line that has target color by a color sensor. When a color sensor finds the target color, the white cane informs a white cane user that he/she is on the navigation line by vibration. So, only following this vibration, the user can reach the destination. However, at some landmark points, guidance is necessary. At these points, an IC tag is set under the navigation line. The cane makes communication with the tag and informs the user about the land mark pint by pre recorded voice. Ten normal subjects who were blindfolded were tested with our developed system. All of them could walk along navigation line. And the IC tag information system worked well. Therefore, we have concluded that our system will be a very valuable one to support activities of the visually impaired.

A Wolf-Rayet-Like Progenitor of SN 2013cu from Spectral Observations of a Stellar Wind

NASA Technical Reports Server (NTRS)

Gal-Yam, Avishay; Arcavi, I.; Ofek, E. O.; Ben-Ami, S.; Cenko, S. B.; Kasliwal, M. M.; Cao, Y.; Yaron, O.; Tal, D.; Silverman, J. M.;

Phytochemical and cytotoxic studies on the roots of Euphorbia fischeriana.

PubMed

Shi, Qun; Sun, Yi-Wei; Meng, Dali

2017-01-15

With the aim of supporting the folk applications of Euphorbia fischeriana, a phytochemical study was performed, which led to the discovery of 9 compounds, including three new ones (1-3) and six known ones (4-9). Their structures were determined by 1D, 2D NMR, and HRESIMS analysis. In the cytotoxic assays on Hep-3B cell line, 2 showed stronger inhibitory effects (IC 50 8.1μmol/L) than that of positive control, and 1, 8 and 9 also gave inhibitory effects in a certain degree with IC 50 values of 12.5, 12.0 and 18.7μmol/L, respectively. While on A549, the cytotoxic activities of 1 (IC 50 11.9μmol/L) and 8 (IC 50 9.4μmol/L) were superior to that of 5-Fu, and those of 4 and 9 were moderate with IC 50 values of 28.2 and 29.8μmol/L, respectively. In addition, both petroleum ether and dichloromethane extracts showed cytotoxic activities with different degree, while n-butanol extracts had no effect. The results clarified that the low-polarity fractions of E. fischeriana, including triterpenoids, abietane and tigliane-type diterpenoids might be the potential bioactive ingredients which will exert strong antitumor effects. Copyright © 2016 Elsevier Ltd. All rights reserved.

Transforming and differentiation-inducing potential of constitutively activated c-kit mutant genes in the IC-2 murine interleukin-3-dependent mast cell line.

PubMed Central

Hashimoto, K.; Tsujimura, T.; Moriyama, Y.; Yamatodani, A.; Kimura, M.; Tohya, K.; Morimoto, M.; Kitayama, H.; Kanakura, Y.; Kitamura, Y.

1996-01-01

Two mutations of c-kit receptor tyrosine kinase (KIT), valine-559 to glycine (G559) and aspartic acid-814 to valine (V814), resulted in its constitutive activation. To examine the transforming and differentiation-inducing potential of the mutant KIT, we used the murine interleukin-3-dependent IC-2 mast cell line as a transfectant. The IC-2 cells contained few basophilic granules and did not express KIT on the surface. The KITG559 or KITV814 gene was introduced into IC-2 cells using a retroviral vector. KITG559 and KITV814 expressed in IC-2 cells were constitutively phosphorylated on tyrosine and demonstrated kinase activity in the absence of stem cell factor, which is a ligand for KIT. IC-2 cells expressing either KITG559 or KITV814 (IC-2G559 or IC-2V814 cells) showed factor-independent growth in suspension culture and produced tumors in nude athymic mice. In addition, IC-2G559 and IC-2V814 cells showed a more mature phenotype compared with the phenotype of the original IC-2 cells, especially after transplantation into nude mice. The number of basophilic granules and the content of histamine increased remarkably. KITG559 and KITV814 also influenced the transcriptional phenotype of mouse mast cell proteases (MMCP) in IC-2 cells. The expression of MMCP-2, MMCP-4, and MMCP-6 was much greater in IC-2G559 and IC-2V814 cells than in the original IC-2 cells. The results indicated that constitutively activated KIT had not only oncogenic activity but also differentiation-inducing activity in mast cells. Images Figure 1 Figure 4 Figure 5 Figure 6 PMID:8546206

Multidrug resistance-selective antiproliferative activity of Piper amide alkaloids and synthetic analogues.

PubMed

Wang, Yue-Hu; Goto, Masuo; Wang, Li-Ting; Hsieh, Kan-Yen; Morris-Natschke, Susan L; Tang, Gui-Hua; Long, Chun-Lin; Lee, Kuo-Hsiung

2014-10-15

Twenty-five amide alkaloids (1-25) from Piper boehmeriifolium and 10 synthetic amide alkaloid derivatives (39-48) were evaluated for antiproliferative activity against eight human tumor cell lines, including chemosensitive and multidrug-resistant (MDR) cell lines. The results suggested tumor type-selectivity. 1-[7-(3,4,5-Trimethoxyphenyl)heptanoyl]piperidine (46) exhibited the best inhibitory activity (IC50=4.94 μM) against the P-glycoprotein (P-gp)-overexpressing KBvin MDR sub-line, while it and all other tested compounds, except 9, were inactive (IC50 >40 μM) against MDA-MB-231 and SK-BR-3. Structure-activity relationships (SARs) indicated that (i) 3,4,5-trimethoxy phenyl substitution is critical for selectivity against KBvin, (ii) the 4-methoxy group in this pattern is crucial for antiproliferative activity, (iii) double bonds in the side chain are not needed for activity, and (iv), in arylalkenylacyl amide alkaloids, replacement of an isobutylamino group with pyrrolidin-1-yl or piperidin-1-yl significantly improved activity. Further study on Piper amides is warranted, particularly whether side chain length affects the ability to overcome the MDR cancer phenotype. Copyright © 2014 Elsevier Ltd. All rights reserved.

Evaluating Possible Heating Mechanisms Using the Transition Region Line Profiles of Late-Type Stars

NASA Technical Reports Server (NTRS)

Wood, Brian E.; Linsky, Jeffrey L.; Ayres, Thomas R.

1997-01-01

Our analysis of high-resolution Goddard High-Resolution Spectrograph (GHRS) spectra of late-type stars shows that the Si IV and C IV lines formed near 10(exp 5) K can be decomposed into the sum of two Gaussians, a broad component and a narrow component. We find that the flux contribution of the broad components is correlated with both the C IV and X-ray surface fluxes. For main-sequence stars, the widths of the narrow components suggest subsonic nonthermal velocities, and there appears to be a tight correlation between these nonthermal velocities and stellar surface gravity [xi(sub nc) varies as g(sup (-.68 +/-.07))]. For evolved stars with lower surface gravities, the nonthermal velocities suggested by the narrow components are at or just above the sound speed. Nonthermal velocities computed from the widths of the broad components are always highly supersonic. We propose that the broad components are diagnostics for microflare heating. Turbulent dissipation and Alfven waves are both viable candidates for the narrow component heating mechanism. A solar analog for the broad components might be the 'explosive events' detected by the High-Resolution Telescope and Spectrograph (HRTS) experiment. The broad component we observe for the Si IV lambda 1394 line of alpha Cen A, a star that is nearly identical to the Sun, has a FWHM of 109 +/- 10 km/s and is blueshifted by 9 +/- 3 km/s relative to the narrow component. Both of these properties are consistent with the properties of the solar explosive events. However, the alpha Cen A broad component accounts for 25% +/- 4% of the total Si IV line flux, while solar explosive events are currently thought to account for no more than 5% of the Sun's total transition region emission. This discrepancy must be resolved before the connection between broad components and explosive events can be positively established. In addition to our analysis of the Si IV and C IV lines of many stars, we also provide a more thorough analysis of all of the available GHRS data for alpha Cen A (G2 V) and alpha Cen B (K1 V). We find that the transition region lines of both stars have redshifts almost identical to those observed on the Sun: showing an increase with line formation temperature up to about log T = 5.2 and then a rapid decrease. Using the O IV] lines as density diagnostics, we compute electron densities of log n(sub e) = 9.65 +/- 0.20 and log n(sub e) = 9.50 +/- 0.30 for alpha Cen A and alpha Cen B, respectively.

LOSS Revisited. I. Unraveling Correlations between Supernova Rates and Galaxy Properties, as Measured in a Reanalysis of the Lick Observatory Supernova Search

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

Graur, Or; Bianco, Federica B.; Huang, Shan

Most types of supernovae (SNe) have yet to be connected with their progenitor stellar systems. Here, we reanalyze the 10-year SN sample collected during 1998–2008 by the Lick Observatory Supernova Search (LOSS) in order to constrain the progenitors of SNe Ia and stripped-envelope SNe (SE SNe, i.e., SNe IIb, Ib, Ic, and broad-lined Ic). We matched the LOSS galaxy sample with spectroscopy from the Sloan Digital Sky Survey and measured SN rates as a function of galaxy stellar mass, specific star formation rate, and oxygen abundance (metallicity). We find significant correlations between the SN rates and all three galaxy properties.more » The SN Ia correlations are consistent with other measurements, as well as with our previous explanation of these measurements in the form of a combination of the SN Ia delay-time distribution and the correlation between galaxy mass and age. The ratio between the SE SN and SN II rates declines significantly in low-mass galaxies. This rules out single stars as SE SN progenitors, and is consistent with predictions from binary-system progenitor models. Using well-known galaxy scaling relations, any correlation between the rates and one of the galaxy properties examined here can be expressed as a correlation with the other two. These redundant correlations preclude us from establishing causality—that is, from ascertaining which of the galaxy properties (or their combination) is the physical driver for the difference between the SE SN and SN II rates. We outline several methods that have the potential to overcome this problem in future works.« less

LOSS Revisited. I. Unraveling Correlations Between Supernova Rates and Galaxy Properties, as Measured in a Reanalysis of the Lick Observatory Supernova Search

NASA Astrophysics Data System (ADS)

Graur, Or; Bianco, Federica B.; Huang, Shan; Modjaz, Maryam; Shivvers, Isaac; Filippenko, Alexei V.; Li, Weidong; Eldridge, J. J.

2017-03-01

Most types of supernovae (SNe) have yet to be connected with their progenitor stellar systems. Here, we reanalyze the 10-year SN sample collected during 1998-2008 by the Lick Observatory Supernova Search (LOSS) in order to constrain the progenitors of SNe Ia and stripped-envelope SNe (SE SNe, I.e., SNe IIb, Ib, Ic, and broad-lined Ic). We matched the LOSS galaxy sample with spectroscopy from the Sloan Digital Sky Survey and measured SN rates as a function of galaxy stellar mass, specific star formation rate, and oxygen abundance (metallicity). We find significant correlations between the SN rates and all three galaxy properties. The SN Ia correlations are consistent with other measurements, as well as with our previous explanation of these measurements in the form of a combination of the SN Ia delay-time distribution and the correlation between galaxy mass and age. The ratio between the SE SN and SN II rates declines significantly in low-mass galaxies. This rules out single stars as SE SN progenitors, and is consistent with predictions from binary-system progenitor models. Using well-known galaxy scaling relations, any correlation between the rates and one of the galaxy properties examined here can be expressed as a correlation with the other two. These redundant correlations preclude us from establishing causality—that is, from ascertaining which of the galaxy properties (or their combination) is the physical driver for the difference between the SE SN and SN II rates. We outline several methods that have the potential to overcome this problem in future works.

VizieR Online Data Catalog: Lick Observatory Supernova Search (LOSS) revisited (Graur+, 2017)

NASA Astrophysics Data System (ADS)

Graur, O.; Bianco, F. B.; Huang, S.; Modjaz, M.; Shivvers, I.; Filippenko, A. V.; Li, W.; Eldridge, J. J.

2017-10-01

Most types of supernovae (SNe) have yet to be connected with their progenitor stellar systems. Here, we reanalyze the 10-year SN sample collected during 1998-2008 by the Lick Observatory Supernova Search (LOSS; see Leaman+, 2011, J/MNRAS/412/1419) in order to constrain the progenitors of SNe Ia and stripped-envelope SNe (SE SNe, i.e., SNe IIb, Ib, Ic, and broad-lined Ic). We matched the LOSS galaxy sample with spectroscopy from the Sloan Digital Sky Survey (SDSS) and measured SN rates as a function of galaxy stellar mass, specific star formation rate, and oxygen abundance (metallicity). We find significant correlations between the SN rates and all three galaxy properties. The SN Ia correlations are consistent with other measurements, as well as with our previous explanation of these measurements in the form of a combination of the SN Ia delay-time distribution and the correlation between galaxy mass and age. The ratio between the SE SN and SN II rates declines significantly in low-mass galaxies. This rules out single stars as SE SN progenitors, and is consistent with predictions from binary-system progenitor models. Using well-known galaxy scaling relations, any correlation between the rates and one of the galaxy properties examined here can be expressed as a correlation with the other two. These redundant correlations preclude us from establishing causality-that is, from ascertaining which of the galaxy properties (or their combination) is the physical driver for the difference between the SE SN and SN II rates. We outline several methods that have the potential to overcome this problem in future works. (7 data files).

Synthesis, stereochemistry determination, pharmacological studies and quantum chemical analyses of bisthiazolidinone derivative

NASA Astrophysics Data System (ADS)

Mushtaque, Md.; Avecilla, Fernando; Hafeez, Zubair Bin; Jahan, Meriyam; Khan, Md. Shahzad; Rizvi, M. Moshahid A.; Khan, Mohd. Shahid; Srivastava, Anurag; Mallik, Anwesha; Verma, Saurabh

2017-01-01

A new compound (3) bisthaizolidinone derivative was synthesized by Knoevenagel condensation reaction. The structure of synthesized compound was elucidated by different spectral techniques and X-ray diffraction studies. The stereochemistry of the compound (3) was determined by 1Hsbnd 1H NOESY, 1Hsbnd 1H NMR COSY and single crystal X-ray diffraction studies as (Z, Z)-configuration. The computational quantum chemical studies of compound(3) like, IR, UV, NBO analysis were performed by DFT with Becke-3-Lee-Yang-Parr (B3LYP) exchange-correlation functional in combination with 6-311++G(d,p) basis sets. The DNA-binding of compound (3) exhibited a moderate binding constant (Kb = 1 × 105 Lmol-1) with hypochromic shift. The molecular docking displayed good binding affinity -7.18 kcal/mol. The MTT assay of compound (3) was screened against different cancerous cell lines, HepG2, Siha, Hela and MCF-7. Studies against these cell lines depicted that the screened compound (3) showed potent inhibitory activity against HepG2 cell (IC50 = 7.5 μM) followed by MCF-7 (IC50 = 52.0 μM), Siha (IC50 = 66.98 μM), Hela (IC50 = 74.83 μM) cell lines, and non-toxic effect against non-cancerous HEK-293 cells (IC50 = 287.89 μM) at the concentration range (0-300) μM. Furthermore, cell cycle perturbation was performed on HepG2 & Siha cell lines and observed that cells were arrested in G2/M in HepG2, and G0/G1 in Siha cell lines with respect to untreated control. Hence, compound (3) possesses potent anti-cancerous activity against HepG2 cell line.

Fermi monitoring of radio-loud narrow-line Seyfert 1 galaxies

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

Paliya, Vaidehi S.; Stalin, C. S.; Ravikumar, C. D., E-mail: vaidehi@iiap.res.in

2015-02-01

We present detailed analysis of the γ-ray flux variability and spectral properties of the five radio-loud narrow line Seyfert 1 (RL-NLSy1) galaxies, detected by the Large Area Telescope on board the Fermi Gamma-Ray Space Telescope, namely 1H 0323+342, SBS 0846+513, PMN J0948+0022, PKS 1502+036, and PKS 2004−447. The first three sources show significant flux variations, including the rapid variability of a few hours by 1H 0323+342. The average γ-ray spectrum of 1H 0323+342 and PMN J0948+0022 shows deviation from a simple power-law (PL) behavior, whereas the PL model gives a better fit for the other three sources. The spectra ofmore » 1H 0323+342, SBS 0846+513, and PMN J0948+0022, which are in low, flaring, and moderately active states, respectively, show significant curvature. Such curvature in the γ-ray spectrum of 1H 0323+342 and PMN J0948+0022 could be due to the emission region located inside the broad line region (BLR) where the primary mechanism of the γ-ray emission is inverse-Compton (IC) scattering of BLR photons occurring in the Klein–Nishina regime. The γ-ray emission of SBS 0846+513 is explained by IC scattering of dusty torus photons, which puts the emission region outside the BLR and thus under the Thomson regime. Therefore, the observed curvature of SBS 0846+513 could be intrinsic to the particle energy distribution. The presence of curvature in the γ-ray spectrum and flux variability amplitudes of some of the RL-NLSy1 galaxies suggests that these sources could be akin to low/moderate jet power flat spectrum radio quasars.« less

6-Substituted 3,4-dihydro-naphthalene-2-carboxylic acids: synthesis and structure-activity studies in a novel class of human 5alpha reductase inhibitors.

PubMed

Baston, Eckhard; Salem, Ola I A; Hartmann, Rolf W

2002-10-01

Novel 3,4-dihydro-naphthalene-2-carboxylic acids were synthesized and evaluated for 5alpha reductase inhibitory activity. This enzyme exists in two isoforms and is a pharmacological target for the treatment of benign prostatic hyperplasia, male pattern baldness and acne. In the present study non-steroidal compounds capable of mimicking the transition state of the steroidal substrates were prepared. The synthetic strategy for the preparation of compounds 1-6 consisted of triflation followed by subsequent Heck-type carboxylation or methoxy carbonylation for 6-phenyl-3,4-dihydronaphthalen-2(1H)-one 1c. A Negishi-type coupling reaction between 6-(trifluoro-methanesulfonyloxy)-3,4-dihydro-naphthalene-2-carboxylic acid methyl ester 7b and various aryl bromides led, after further transformations, to 6-substituted 3,4-dihydro-naphthalene-2-carboxylic acids 7-15. In a similar way the corresponding naphthalene-2-carboxylic acids 16 and 17 were obtained. The DU 145 cell line and prostate homogenates served as enzyme sources for the human type 1 and type 2 isozymes, whereas ventral prostate was employed to evaluate rat isozyme inhibitory potency. The most active inhibitors identified in this study were 6-[4-(N,N-dicyclohexylaminocarbonyl)phenyl]-3,4-dihydro-naphthalene-2-carboxylic acid (3) (IC50 = 0.09 microM, rat type 1), 6-[3-(N,N-dicyclohexylaminocarbonyl)phenyl]-3,4-dihydro-naphthalene-2-carboxylic acid (13) (IC50 = 0.75 microM, human type 2; IC50 = 0.81 microM, human type 1) and 6-[4-(N,N-diisopropylamino-carbonyl)phenyl]naphthalene-2-carboxylic acid (16) (IC50 = 0.2 microM, human type 2). The latter compound was shown to deactivate the enzyme in an uncompetitive manner (Ki = 90 nM; Km, Testosterone = 0.8-1.0 microM) similar to the steroidal inhibitor Epristeride. Select inhibitors (13 and 16) were tested in vivo using testosterone propionate-treated, juvenile, orchiectomized SD-rats. None of the compounds was active at a dose of 25 mg/kg. This result might in part be ascribed to the relatively poor in vitro rat isozyme inhibitory potency.

Antiproliferative Activity of Xanthones Isolated from Artocarpus obtusus

PubMed Central

Hashim, Najihah Mohd; Rahmani, Mawardi; Ee, Gwendoline Cheng Lian; Sukari, Mohd Aspollah; Yahayu, Maizatulakmal; Oktima, Winda; Ali, Abd Manaf; Go, Rusea

2012-01-01

An investigation of the chemical constituents in Artocarpus obtusus species led to the isolation of three new xanthones, pyranocycloartobiloxanthone A (1), dihydroartoindonesianin C (2), and pyranocycloartobiloxanthone B (3). The compounds were subjected to antiproliferative assay against human promyelocytic leukemia (HL60), human chronic myeloid leukemia (K562), and human estrogen receptor (ER+) positive breast cancer (MCF7) cell lines. Pyranocycloartobiloxanthone A (1) consistently showed strong cytotoxic activity against the three cell lines compared to the other two with IC50 values of 0.5, 2.0 and 5.0 μg/mL, respectively. Compound (1) was also observed to exert antiproliferative activity and apoptotic promoter towards HL60 and MCF7 cell lines at respective IC50 values. The compound (1) was not toxic towards normal cell lines human nontumorigenic breast cell line (MCF10A) and human peripheral blood mononuclear cells (PBMCs) with IC50 values of more than 30 μg/mL. PMID:21960741

Observation of supernova remnant IC 443 with the Fermi Large Area Telescope

DOE PAGES

Abdo, A. A.

2010-03-03

Here, we report observation of the supernova remnant (SNR) IC 443 (G189.1+3.0) with the Fermi Gamma-ray Space Telescope Large Area Telescope (LAT) in the energy band between 200 MeV and 50 GeV. IC 443 is a shell-type SNR with mixed morphology located off the outer Galactic plane where high-energy emission has been detected in the X-ray, GeV and TeV gamma-ray bands. Past observations suggest IC 443 has been interacting with surrounding interstellar matter. Proximity between dense shocked molecular clouds and GeV-TeV gamma-ray emission regions detected by EGRET, MAGIC, and VERITAS suggests an interpretation that cosmic-ray (CR) particles are accelerated by the SNR. We accurately characterize the gamma-ray emission produced by the CRs accelerated at IC 443 using the high gamma-ray statistics and broad energy coverage provided by the LAT. The emission region is extended in the energy band with θ 68 = 0more » $$°\\atop{.}$$27 ± 0fdg01(stat) ± 0$$°\\atop{.}$$03(sys) for an assumed two-dimensional Gaussian profile and overlaps almost completely with the extended source region of VERITAS. Its centroid is displaced significantly from the known pulsar wind nebula (PWN) which suggests the PWN is not the major contributor in the present energy band. The observed spectrum changes its power-law slope continuously and continues smoothly to the MAGIC and VERITAS data points. Furthermore, the combined gamma-ray spectrum (200 MeV« less

Cranberry Proanthocyanidins are Cytotoxic to Human Cancer Cells and Sensitize Platinum-Resistant Ovarian Cancer Cells to Paraplatin

PubMed Central

Singh, Ajay P.; Singh, Rakesh K.; Kim, Kyu Kwang; Satyan, K. S.; Nussbaum, Roger; Torres, Monica; Brard, Laurent; Vorsa, Nicholi

2010-01-01

Polyphenolic extracts of the principal flavonoid classes present in cranberry were screened in vitro for cytotoxicity against solid tumor cells lines, identifying two fractions composed principally of proanthocyanidins (PACs) with potential anticancer activity. Matrix-Assisted Laser Desorption/Ionization Time-Of-Flight Mass Spectrometry (MALDI-TOF-MS) analysis of the proanthocyanidins (PACs) fractions indicated the presence of A-type PACs with 1–4 linkages containing between 2–8 epicatechin units with a maximum of 1 epigallocatechin unit. PACs exhibited in vitro cytotoxicity against platinum-resistant human ovarian, neuroblastoma and prostate cancer cell lines (IC50 = 79–479 μg/mL) but were non-cytotoxic to lung fibroblast cells (IC50 > 1000 μg/ml). SKOV-3 ovarian cancer cells treated with PACs exhibited classic apoptotic changes. PACs acted synergistically with paraplatin in SKOV-3 cells. Pretreatment of SKOV-3 cells with PACs (106 μg/ ml) resulted in a significant reduction of the paraplatin IC50 value. Similarly, in a BrdU incorporation assay, co-treatment of SKOV-3 cells with PACs and paraplatin revealed reduced cell proliferation at lower concentrations than with either individually. In SKOV-3 cell cultures co-treated with PAC-1 and paraplatin, an HPLC analysis indicated differential quantitative presence of various PAC oligomers such as DP-8, -9, -11 and -14 indicating either selective binding or uptake. Cranberry proanthocyanidins exhibit cell-line specific cytotoxicity, induce apoptotic markers and augment cytotoxicity of paraplatin in platinum-resistant SKOV-3 ovarian cancer cells. PMID:19172579

Biosynthesis of Silver Nanoparticles from Protium serratum and Investigation of their Potential Impacts on Food Safety and Control

PubMed Central

Mohanta, Yugal K.; Panda, Sujogya K.; Bastia, Akshaya K.; Mohanta, Tapan K.

2017-01-01

Silver nanoparticles play an integral part in the evolution of new antimicrobials against the broad ranges of pathogenic microorganisms. Recently, biological synthesis of metal nanoparticles using plant extracts has been successfully consummated. In the present study, the biosynthesis of silver nanoparticles (AgNPs) was conducted using the leaf extract of plant Protium serratum, having novel ethnomedicinal. The synthesized AgNPs were characterized using UV-Visible spectroscopy, dynamic light scattering spectroscopy (DLS), Fourier transform infrared spectroscopy (FTIR), and scanning electron microscopy. The DLS study revealed the surface charge of the resulted nanoparticles that was highly negative, i.e., −25.0 ± 7.84 mV and the size was 74.56 ± 0.46 nm. The phytochemical and FTIR analysis confirmed the role of water-soluble phyto-compounds for the reduction of silver ions to silver nanoparticles. The potential antibacterial activity of AgNPs was studied against the food borne pathogens viz. Pseudomonas aeruginosa (IC50 = 74.26 ± 0.14 μg/ml), Escherichia coli (IC50 = 84.28 ± 0.36 μg/ml), Bacillus subtilis (IC50 = 94.43 ± 0.4236 μg/ml). The in vitro antioxidant potential of AgNPs was evaluated using 1, 1-diphenyl-2-picryl-hydrazil (IC50 = 6.78 ± 0.15 μg/ml) and hydroxyl radical assay (IC50 = 89.58 ± 1.15 μg/ml). In addition, the cytotoxicity of AgNPs was performed against fibroblast cell line L-929 to evaluate their biocompatibility. The overall results of the present investigation displayed the potential use of P. serratum leaf extract as a good bio-resource for the biosynthesis of AgNPs and their implementation in diverse applications, specifically as antibacterial agent in food packaging and preservation to combat against various food borne pathogenic bacteria along with its pharmaceutical and biomedical applications. PMID:28458659

50 Years of ``Scaling'' Jack Kilby's Invention

NASA Astrophysics Data System (ADS)

Doering, Robert

2008-03-01

This year is the 50th anniversary of Jack Kilby's 1958 invention of the integrated circuit (IC), for which he won the 2000 Nobel Prize in Physics. Since that invention in a laboratory at Texas Instruments, IC components have been continuously miniaturized, which has resulted in exponential improvement trends in their performance, energy efficiency, and cost per function. These improvements have created a semiconductor industry that has grown to over 250B in annual sales. The process of reducing integrated-circuit component size and associated parameters in a coordinated fashion is traditionally called ``feature-size scaling.'' Kilby's original circuit had active (transistor) and passive (resistor, capacitor) components with dimensions of a few millimeters. Today, the minimum feature sizes on integrated circuits are less than 30 nanometers for patterned line widths and down to about one nanometer for film thicknesses. Thus, we have achieved about five orders of magnitude in linear-dimension scaling over the past fifty years, which has resulted in about ten orders of magnitude increase in the density of IC components, a representation of ``Moore's Law.'' As IC features are approaching atomic dimensions, increasing emphasis is now being given to the parallel effort of further diversifying the types of components in integrated circuits. This is called ``functional scaling'' and ``more then Moore.'' Of course, the enablers for both types of scaling have been developed at many laboratories around the world. This talk will review a few of the highlights in scaling and its applications from R&D projects at Texas Instruments.

A novel fluorescence-quenching immunochromatographic sensor for detection of the heavy metal chromium.

PubMed

Fu, QiangQiang; Tang, Yong; Shi, CongYing; Zhang, XiaoLi; Xiang, JunJian; Liu, Xi

2013-11-15

A novel fluorescence quenching immunochromatographic sensor (ICS) was developed for detecting chromium (Cr(3+)) within 15 min utilizing the fluorescence quenching function of gold nanoparticles (Au-NPs). The sensor performed with a positive readout. When the low concentrations of Cr(3+) samples were applied, detection signals of the test line (T line) were quenched, whereas when higher concentration Cr(3+) samples (1.56 ng/mL) were applied, the detection signal of the T line appeared. The detection signal intensity of the T line increased with increasing concentrations of Cr(3+). The low detection limit of developed fluorescence quenching ICS was 1.56 ng/mL. The fluorescence quenching ICS has a linear range of detection of Cr(3+) comprising between 6.25 ng/mL to 800 ng/mL. The recoveries of the fluorescence quenching ICS to detect Cr(3+) in tap water ranged from 94.7% to 101.7%. This result indicated that the developed sensor gave higher sensitivity and reliable reproducibility. It could provide a general detection method for small analyte in water samples. Copyright © 2013 Elsevier B.V. All rights reserved.

SN 2017dio: A Type-Ic Supernova Exploding in a Hydrogen-rich Circumstellar Medium

NASA Astrophysics Data System (ADS)

Kuncarayakti, Hanindyo; Maeda, Keiichi; Ashall, Christopher J.; Prentice, Simon J.; Mattila, Seppo; Kankare, Erkki; Fransson, Claes; Lundqvist, Peter; Pastorello, Andrea; Leloudas, Giorgos; Anderson, Joseph P.; Benetti, Stefano; Bersten, Melina C.; Cappellaro, Enrico; Cartier, Régis; Denneau, Larry; Della Valle, Massimo; Elias-Rosa, Nancy; Folatelli, Gastón; Fraser, Morgan; Galbany, Lluís; Gall, Christa; Gal-Yam, Avishay; Gutiérrez, Claudia P.; Hamanowicz, Aleksandra; Heinze, Ari; Inserra, Cosimo; Kangas, Tuomas; Mazzali, Paolo; Melandri, Andrea; Pignata, Giuliano; Rest, Armin; Reynolds, Thomas; Roy, Rupak; Smartt, Stephen J.; Smith, Ken W.; Sollerman, Jesper; Somero, Auni; Stalder, Brian; Stritzinger, Maximilian; Taddia, Francesco; Tomasella, Lina; Tonry, John; Weiland, Henry; Young, David R.

2018-02-01

SN 2017dio shows both spectral characteristics of a type-Ic supernova (SN) and signs of a hydrogen-rich circumstellar medium (CSM). Prominent, narrow emission lines of H and He are superposed on the continuum. Subsequent evolution revealed that the SN ejecta are interacting with the CSM. The initial SN Ic identification was confirmed by removing the CSM interaction component from the spectrum and comparing with known SNe Ic and, reversely, adding a CSM interaction component to the spectra of known SNe Ic and comparing them to SN 2017dio. Excellent agreement was obtained with both procedures, reinforcing the SN Ic classification. The light curve constrains the pre-interaction SN Ic peak absolute magnitude to be around {M}g=-17.6 mag. No evidence of significant extinction is found, ruling out a brighter luminosity required by an SN Ia classification. These pieces of evidence support the view that SN 2017dio is an SN Ic, and therefore the first firm case of an SN Ic with signatures of hydrogen-rich CSM in the early spectrum. The CSM is unlikely to have been shaped by steady-state stellar winds. The mass loss of the progenitor star must have been intense, \\dot{M}∼ 0.02{({ε }{{H}α }/0.01)}-1 ({v}{wind}/500 km s‑1) ({v}{shock}/10,000 km s‑1)‑3 M ⊙ yr‑1, peaking at a few decades before the SN. Such a high mass-loss rate might have been experienced by the progenitor through eruptions or binary stripping. Based on observations made with the NOT, operated by the Nordic Optical Telescope Scientific Association at the Observatorio del Roque de los Muchachos, La Palma, Spain, of the Instituto de Astrofisica de Canarias. This work is based (in part) on observations collected at the European Organisation for Astronomical Research in the Southern Hemisphere, Chile as part of PESSTO, (the Public ESO Spectroscopic Survey for Transient Objects Survey) ESO program 188.D-3003, 191.D-0935, 197.D-1075. Based on observations made with the Liverpool Telescope operated on the island of La Palma by Liverpool John Moores University in the Spanish Observatorio del Roque de los Muchachos of the Instituto de Astrofisica de Canarias with financial support from the UK Science and Technology Facilities Council.

Propolis from the Stingless Bee Trigona incisa from East Kalimantan, Indonesia, Induces In Vitro Cytotoxicity and Apoptosis in Cancer Cell lines.

PubMed

Kustiawan, Paula M; Phuwapraisirisan, Preecha; Puthong, Songchan; Palaga, Tanapat; Arung, Enos T; Chanchao, Chanpen

2015-01-01

Previously, stingless bee (Trigona spp.) products from East Kalimantan, Indonesia, were successfully screened for in vitro antiproliferative activity against human cancer derived cell lines. It was established that propolis from T. incisa presented the highest in vitro cytotoxicity against the SW620 colon cancer cell line (6% cell survival in 20 μg/mL). Propolis from T. incisa was extracted with methanol and further partitioned with n-hexane, ethyl acetate and methanol. The in vitro cytotoxicity of the extracts was assessed by the MTT assay against human colon (SW620), liver (Hep-G2), gastric (KATO-III), lung (Chago) and breast (BT474) cancer derived cell lines. The active fractions were further enriched by silica gel quick column, absorption and size exclusion chromatography. The purity of each fraction was checked by thin layer chromatography. Cytotoxicity in BT-474 cells induced by cardanol compared to doxorubicin were evaluated by MTT assay, induction of cell cycle arrest and cell death by flow cytometric analysis of propidium iodide and annexin-V stained cells. A cardol isomer was found to be the major compound in one active fraction (F45) of T. incisa propolis, with a cytotoxicity against the SW620 (IC50 of 4.51±0.76 μg/mL), KATO-III (IC50 of 6.06±0.39 μg/mL), Hep-G2 (IC50 of 0.71±0.22 μg/mL), Chago I (IC50 of 0.81±0.18 μg/mL) and BT474 (IC50 of 4.28±0.14 μg/mL) cell lines. Early apoptosis (programmed cell death) of SW620 cells was induced by the cardol containing F45 fraction at the IC50 and IC80 concentrations, respectively, within 2-6 h of incubation. In addition, the F45 fraction induced cell cycle arrest at the G1 subphase. Indonesian stingless bee (T. incisa) propolis had moderately potent in vitro anticancer activity on human cancer derived cell lines. Cardol or 5-pentadecyl resorcinol was identified as a major active compound and induced apoptosis in SW620 cells in an early period (≤6 h) and cell cycle arrest at the G1 subphase. Thus, cardol is a potential candidate for cancer chemotherapy.

The Type Ic SN 2007gr: a census of the ejecta from late-time optical-infrared spectra

NASA Astrophysics Data System (ADS)

Mazzali, Paolo A.; Maurer, I.; Valenti, S.; Kotak, R.; Hunter, D.

2010-10-01

Nebular spectra of supernovae (SNe) offer an unimpeded view of the inner region of the ejecta, where most nucleosynthesis takes place. Optical spectra cover most, but not all, of the emitting elements and therefore offer only a partial view of the products of the explosion. Simultaneous optical-infrared spectra, on the other hand, contain emission lines of all important elements, from C and O through to the intermediate mass elements (IME) Mg, Si, S, Ca and to Fe and Ni. In particular, Si and S are best seen in the IR. The availability of IR data makes it possible to explore in greater detail the results of the explosion. SN2007gr is the first Type Ic SN for which such data are available. Modelling the spectra with a non-local thermodynamic equilibrium (NLTE) code reveals that the inner ejecta contain ~1Msolar of material within a velocity of ~4500kms-1. The same mass of 56Ni derived from the light-curve peak (0.076Msolar) was used to power the spectrum, yielding consistent results. Oxygen is the dominant element, contributing ~0.8Msolar. The C/O ratio is <0.2. IME account for ~0.1Msolar. This confirms that SN2007gr was the explosion of a low-mass CO core, probably the result of a star of main-sequence mass ~15Msolar. The ratios of the CaII lines, and those of FeII, are sensitive to the assumed degree of clumping. In particular, the optical lines of [FeII] become stronger, relative to the IR lines, for higher degrees of clumping.

Polarization of the changing-look quasar J1011+5442

NASA Astrophysics Data System (ADS)

Hutsemékers, D.; Agís González, B.; Sluse, D.; Ramos Almeida, C.; Acosta Pulido, J.-A.

2017-07-01

If the disappearance of the broad emission lines observed in changing-look quasars were caused by the obscuration of the quasar core through moving dust clouds in the torus, high linear polarization typical of type 2 quasars would be expected. We measured the polarization of the changing-look quasar J1011+5442 in which the broad emission lines have disappeared between 2003 and 2015. We found a polarization degree compatible with null polarization. This measurement suggests that the observed change of look is not due to a change of obscuration hiding the continuum source and the broad line region, and that the quasar is seen close to the system axis. Our results thus support the idea that the vanishing of the broad emission lines in J1011+5442 is due to an intrinsic dimming of the ionizing continuum source that is most likely caused by a rapid decrease in the rate of accretion onto the supermassive black hole. Based on observations made with the William Herschel telescope operated on the island of La Palma by the Isaac Newton Group of Telescopes in the Spanish Observatorio del Roque de los Muchachos of the Instituto de Astrofísica de Canarias.

Cost-effectiveness analysis of anidulafungin for the treatment of candidaemia and other forms of invasive candidiasis.

PubMed

Auzinger, Georg; Playford, E Geoffrey; Graham, Christopher N; Knox, Hediyyih N; Weinstein, David; Kantecki, Michal; Schlamm, Haran; Charbonneau, Claudie

2015-10-26

Candidaemia and other forms of invasive candidiasis (C/IC) in the intensive care unit are challenging conditions that are associated with high rates of mortality. New guidelines from the European Society for Clinical Microbiology and Infectious Diseases strongly recommend echinocandins for the first-line treatment of C/IC. Here, a cost-effectiveness model was developed from the United Kingdom perspective to examine the costs and outcomes of antifungal treatment for C/IC based on the European Society for Clinical Microbiology and Infectious Diseases guidelines. Costs and treatment outcomes with the echinocandin anidulafungin were compared with those for caspofungin, micafungin and fluconazole. The model included non-neutropenic patients aged ≥16 years with confirmed C/IC who were receiving intravenous first-line treatment. Patients were categorised as either a clinical success or failure (patients with persistent/breakthrough infection); successfully treated patients switched to oral therapy, while patients categorised as clinical failures switched to a different antifungal class. Other inputs were all-cause mortality at 6 weeks, costs of treatment-related adverse events and other medical resource utilisation costs. Resource use was derived from the published literature and from discussion with clinical experts. Drug-acquisition/administration costs were taken from standard United Kingdom costing sources. The model indicated that first-line anidulafungin could be considered cost-effective versus fluconazole (incremental cost-effectiveness ratio £813 per life-year gained) for the treatment of C/IC. Anidulafungin was cost-saving versus caspofungin and micafungin due to lower total costs and a higher rate of survival combined with a higher probability of clinical success. European Society for Clinical Microbiology and Infectious Diseases guidelines recommend echinocandins for the first-line treatment of C/IC; our model indicated that anidulafungin marries clinical effectiveness and cost-effectiveness. From the United Kingdom perspective, anidulafungin was cost-effective compared with fluconazole for the treatment of C/IC and was cost-saving versus the other echinocandins.

The antiviral effects of RSV fusion inhibitor, MDT-637, on clinical isolates, vs its achievable concentrations in the human respiratory tract and comparison to ribavirin.

PubMed

Kim, Young-In; Pareek, Rajat; Murphy, Ryan; Harrison, Lisa; Farrell, Eric; Cook, Robert; DeVincenzo, John

2017-11-01

Respiratory syncytial virus (RSV) viral load and disease severity associate, and the timing of viral load and disease run in parallel. An antiviral must be broadly effective against the natural spectrum of RSV genotypes and must attain concentrations capable of inhibiting viral replication within the human respiratory tract. We evaluated a novel RSV fusion inhibitor, MDT-637, and compared it with ribavirin for therapeutic effect in vitro to identify relative therapeutic doses achievable in humans. MDT-637 and ribavirin were co-incubated with RSV in HEp-2 cells. Quantitative PCR assessed viral concentrations; 50% inhibitory concentrations (IC 50 ) were compared to achievable human MDT-637 and ribavirin peak and trough concentrations. The IC 50 for MDT-637 and ribavirin (against RSV-A Long) was 1.42 and 16 973 ng/mL, respectively. The ratio of achievable peak respiratory secretion concentration to IC 50 was 6041-fold for MDT-637 and 25-fold for aerosolized ribavirin. The ratio of trough concentration to IC 50 was 1481-fold for MDT-637 and 3.29-fold for aerosolized ribavirin. Maximal peak and trough levels of oral or intravenous ribavirin were significantly lower than their IC 50 s. We also measured MDT-637 IC 50 s in 3 lab strains and 4 clinical strains. The IC 50 s ranged from 0.36 to 3.4 ng/mL. Achievable human MDT-637 concentrations in respiratory secretions exceed the IC 50 s by factors from hundreds to thousands of times greater than does ribavirin. Furthermore, MDT-637 has broad in vitro antiviral activity on clinical strains of different RSV genotypes and clades. Together, these data imply that MDT-637 may produce a superior clinical effect compared to ribavirin on natural RSV infections. © 2017 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

Noise suppression and crosstalk analysis of on-chip magnetic film-type noise suppressor

NASA Astrophysics Data System (ADS)

Ma, Jingyan; Muroga, Sho; Endo, Yasushi; Hashi, Shuichiro; Naoe, Masayuki; Yokoyama, Hiroo; Hayashi, Yoshiaki; Ishiyama, Kazushi

2018-05-01

This paper discusses near field, conduction and crosstalk noise suppression of magnetic films with uniaxial anisotropy on transmission lines for a film-type noise suppressor in the GHz frequency range. The electromagnetic noise suppressions of magnetic films with different permeability and resistivity were measured and simulated with simple microstrip lines. The experimental and simulated results of Co-Zr-Nb and CoPd-CaF2 films agreed with each other. The results indicate that the higher permeability leads to a better near field shielding, and in the frequency range of 2-7 GHz, a higher conduction noise suppression. It also suggests that the higher resistivity results in a better crosstalk suppression in the frequency range below 2 GHz. These results can support the design guidelines of the magnetic film-type noise suppressor used in the next generation IC chip.

Synthesis of 2',4-dihydroxy-3-methoxychalcone and 2',4',4-trihydroxy-3-methoxychalcone as a candidate anticancer against cervical (WiDr), colon (HeLa), and breast (T47d) cancer cell lines in vitro

NASA Astrophysics Data System (ADS)

Matsjeh, Sabirin; Swasono, Respati Tri; Anwar, Chairil; Solikhah, Eti Nurwening; Lestari, Endang

2017-03-01

The compound 2',4-dihydroxy-3-methoxychalcone and 2',4',4-trihydroxy-3-methoxychalcone have been synthesized through Claisen-Schmidt reaction from 2-hydroxyacetophenone and 2,4-dihydroxyacetophenone with 4-hydroxy-3-methoxy benzaldehida (vanillin) in aqueous KOH 40% and KSF montmorillonite as catalyst in methanol. All these products were characterized by FT-IR, TLC Scanner, GC-MS, MS-Direct, and 1H-NMR and 13C-NMR spectrometer. Both of these compounds were tested citotoxycity activity as an anticancer against cervical, colon, and breast cancer cells (Hela, WiDr, and T47D cell lines) using MTT assay in vitro. Dose series given test solution concentration on Hela, WiDr, and T47D cells started from 6,25; 25; 50 and 100 µg/mL with incubation treatment for 24 hours. The result of study showed that the 2',4-dihydroxy-3-methoxychalcone as bright yellow crystal with the melting point of 114-115 °C and the yield of 13.77% and the 2',4',4-trihydroxy-3-methoxychalcone as bright yellow crystals with the melting point of 195-197 °C and the yield of 6%. Other 2',4-dihydroxy-3-methoxychalcone and 2',4',4-trihydroxy-3-methoxychalcone also exhibited cytotoxic activity against the cancer cell lines, with the 2',4',4-trihydroxy-3-methoxychalcone showed greater activities than the 2',4-dihydroxy-3-methoxychalcone in WiDr cell lines. The 2',4-dihydroxy-3-methoxychalcone and 2',4',4-trihydroxy-3-methoxychalcone exhibited strong anticancer activities with IC50 value below 20 µg/mL. The activity of 2',4',4-trihydroxy-3-methoxychalcone showed the most active against Hela and WiDr cell lines with IC50 value 8.53 and 2.66 µg/mL respectively, than T47D cell lines with IC50 value 24.61 µg/mL. The test results cytotoxic of 2',4-dihydroxy-3-methoxychalcone showed the most active against Hela and WiDr cell lines with IC50 value 12.80, 19.57 µg/mL than T47D cell lines with IC50 value of 20.73 µg/mL. IC50 value indicated that 2',4-dihydroxy-3-methoxychalcone and 2',4',4-trihydroxy-3-methoxychalcone potential as inhibitors in Hela, WiDr and T47D cell lines.

New eremophilane-type sesquiterpenes from an Antarctic deepsea derived fungus, Penicillium sp. PR19 N-1.

PubMed

Lin, Aiqun; Wu, Guangwei; Gu, Qianqun; Zhu, Tianjiao; Li, Dehai

2014-07-01

Chemical investigation of an Antarctic deepsea derived fungus Penicillium sp. PR19 N-1 yielded five new eremophilane-type sesquiterpenes 1–5 and a new rare lactam-type eremophilane 6, together with three known compounds 7–9. The structures of these diverse sesquiterpenes were determined by extensive NMR and mass spectroscopic analyses. Compounds 1, 2, 4–6, 8 and 9 were evaluated for their cytotoxities against HL-60 and A-549 human cancer cell lines, and 5 was the most active one with IC50 value of 5.2 lM against the A-549 cells.

One new 19-nor cucurbitane-type triterpenoid from the stems of Momordica charantia.

PubMed

Li, Yong-chao; Xu, Xin-juan; Yang, Jing; Wu, Xing-gang; Fu, Qing-yun

2016-01-01

One new 19-nor cucurbitane-type triterpenoid (3β,9β,25-trihydroxy-7β-methoxy-19-nor-cucurbita-5,23(E)-diene) (1), together with other six known cucurbitane-type triterpenoids (2-7), were isolated from the stems of Momordica charantia L. The chemical structure of 1 was elucidated by extensive 1D NMR and 2D NMR (HSQC, HMBC, COSY and ROESY), MS experiments. Using MTT assay, compound 1 exhibited weak cytotoxicity against HL-60, A-549, and SK-BR-3 cell lines with the IC50 values at 27.3, 32.7 and 26.6 μM, respectively.

Targeted Type 1 phototherapeutic agents using azido-peptide bioconjugates

NASA Astrophysics Data System (ADS)

Rajagopalan, Raghavan; Achilefu, Samuel I.; Jimenez, Hermo N.; Webb, Elizabeth G.; Schmidt, Michelle A.; Bugaj, Joseph E.; Dorshow, Richard B.

2001-07-01

Five peptides binding to somatostatin and bombesin receptors were conjugated to 4-azido-2,3,4,6-tetrafluorophenylbenzoic acid, a Type 1 photosensitizer, at the N-terminal position. The receptor affinities were determined by competition binding assay using two different pancreatic tumor cell lines, CA20948 and AR42-J, that expresses somatostatin-2 (SST-2) and bombesin receptors receptively. All compounds exhibited high receptor specificity, i.e., the IC50 values ranged between 1.0 to 64.0 nM. These conjugates may be useful for targeted Type 1 phototherapy via the generation of nitrenes at the cell surfaces expressing these receptors.

Synthesis and Biological Evaluation of Benzochromenopyrimidinones as Cholinesterase Inhibitors and Potent Antioxidant, Non-Hepatotoxic Agents for Alzheimer's Disease.

PubMed

Dgachi, Youssef; Bautista-Aguilera, Oscar M; Benchekroun, Mohamed; Martin, Hélène; Bonet, Alexandre; Knez, Damijan; Godyń, Justyna; Malawska, Barbara; Gobec, Stanislav; Chioua, Mourad; Janockova, Jana; Soukup, Ondrej; Chabchoub, Fakher; Marco-Contelles, José; Ismaili, Lhassane

2016-05-14

We report herein the straightforward two-step synthesis and biological assessment of novel racemic benzochromenopyrimidinones as non-hepatotoxic, acetylcholinesterase inhibitors with antioxidative properties. Among them, compound 3Bb displayed a mixed-type inhibition of human acetylcholinesterase (IC50 = 1.28 ± 0.03 μM), good antioxidant activity, and also proved to be non-hepatotoxic on human HepG2 cell line.

Two new triterpenoid saponins from the aerial parts of Anemone taipaiensis.

PubMed

Li, Hui; Wang, Xiao-Yang; Wang, Xia-Yin; Hua, Dong; Liu, Yang; Tang, Hai-Feng

2015-05-01

Phytochemical study on the aerial parts of Anemone taipaiensis for the first time led to the isolation of two new oleanane-type triterpenoid saponins 1 and 2, together with four known saponins (3-6). Their structures were elucidated by extensive spectroscopic analysis and chemical evidences. Saponins 2-4 exhibited cytotoxicity against human glioblastoma U251MG cell line with IC50 values ranging from 1.56 to 80.62 μM.

Synthesis, characterization and anticancer studies of Ni(II), Pd(II) and Pt(II) complexes with Schiff base derived from N-methylhydrazinecarbothioamide and 2-hydroxy-5-methoxy-3-nitrobenzaldehyde

NASA Astrophysics Data System (ADS)

Arafath, Md. Azharul; Adam, Farook; Razali, Mohd. R.; Ahmed Hassan, Loiy E.; Ahamed, Mohamed B. Khadeer; Majid, Amin Malik S. A.

2017-02-01

A carbothioamide NSO tridentate Schiff base ligand (HL) and its square planar complexes Na[NiLOAc], Na[PdLOAc] and [PtLdmso] have been synthesized and characterized on the basis of melting point, elemental analysis, FT-IR, 1H NMR, 13C NMR, UV-Vis spectra. The structure of HL was elucidated with X-ray diffraction analysis. In the present study, the synthesized compounds were evaluated for their anticancer properties against three human cancer cell lines breast cancer (MCF-7), cervical (Hela), and colon (HCT-116). In addition, the cytotoxicity of the synthesized compounds was tested on a normal human cell line (human endothelial cell line EA.hy926). Among the tested compounds, the complex [NiLOAc] excelled in halting proliferation of the cervical and colon cancer cells with median inhibitory concentration (IC50) values of 28.33 and 34.4 μM, respectively. The complex, [PdLOAc] demonstrated selective cytotoxicity against breast cancer line MCF-7 with IC50 = 47.5 μM, while HL showed inhibitory effect against colon cancer cell line (HCT-116) with IC50 = 55.66 μM. The complex, [PtLdmso] showed mild activity against breast cancer (MCF-7) and cervical cancer (Hela) cells with IC50 = 64.44 and 68.3 μM, respectively, whereas, it displayed insignificant cytotoxicity against human endothelial cells (EA.hy926) with IC50 > 200 μM. Cancer cells treated with [NiLOAc] showed apoptotic features such as membrane blebbing and DNA condensation. Thus, the findings of the present study demonstrated that the series of metal complexes of HL could form the new lead for development of cancer chemotherapies to treat human cervical, breast and colon malignancies.

Investigation of imatinib loaded surface decorated biodegradable nanocarriers against glioblastoma cell lines: Intracellular uptake and cytotoxicity studies.

PubMed

Khan, Abrar M; Ahmad, Farhan Jalees; Panda, Amulya K; Talegaonkar, Sushama

2016-06-30

Overexpression of P-glycoprotein (P-gp) efflux transporter in glioma cells thwarts the build-up of therapeutic concentration of drugs usually resulting into poor therapeutic outcome. To surmount aforesaid challenge, Imatinib (IMM) loaded Poly-lactide-co-glycolic acid nanoparticles (IMM-PLGA-NPs) were developed and optimized by Box Behnken Design as a new treatment stratagem in malignant glioma. Optimized NPs were functionalized with Pluronic(®) P84, P-gp inhibitor (IMM-PLGA-P84-NPs) which showed size, PDI, zeta potential, drug loading, 182.63±13.56nm, 0.196±0.021, -15.2±1.49mV, 40.63±2.04μg/mg, respectively. Intracellular uptake study conducted on A172, U251MG and C6 glioma cells demonstrated significantly high uptake of IMM through NPs when compared with IMM solution (IMM-S), p<0.001. IMM-PLGA-P84-NPs showed better uptake in P-gp expressing cell line (U251MG and C6) while uncoated NPs showed higher uptake in non-P-gp expressing cell line (A-172). Cytotoxicity studies demonstrated significantly low IC50 for both IMM-PLGA-NPs and IMM-PLGA-P84-NPs when compared with IC50 of IMM-S. IMM-PLGA-P84-NPs showed a significantly low IC50 against P-gp overexpressing cell lines when compared with IC50 of IMM-PLGA-NPs. In contrary, IMM-PLGA-NPs showed lower IC50 against non P-gp expressing cell line. This study demonstrated the feasibility of targeting surface decorated NPs to multidrug resistant gliomas. However, to address its clinical utility extensive in vivo studies are required. Copyright © 2016 Elsevier B.V. All rights reserved.

DISSECTING THE POWER SOURCES OF LOW-LUMINOSITY EMISSION-LINE GALAXY NUCLEI VIA COMPARISON OF HST-STIS AND GROUND-BASED SPECTRA

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

Constantin, Anca; Castillo, Christopher A.; Shields, Joseph C.

Using a sample of ∼100 nearby line-emitting galaxy nuclei, we have built the currently definitive atlas of spectroscopic measurements of Hα and neighboring emission lines at subarcsecond scales. We employ these data in a quantitative comparison of the nebular emission in Hubble Space Telescope (HST) and ground-based apertures, which offer an order-of-magnitude difference in contrast, and provide new statistical constraints on the degree to which transition objects and low-ionization nuclear emission-line regions (LINERs) are powered by an accreting black hole at ≲10 pc. We show that while the small-aperture observations clearly resolve the nebular emission, the aperture dependence in themore » line ratios is generally weak, and this can be explained by gradients in the density of the line-emitting gas: the higher densities in the more nuclear regions potentially flatten the excitation gradients, suppressing the forbidden emission. The transition objects show a threefold increase in the incidence of broad Hα emission in the high-resolution data, as well as the strongest density gradients, supporting the composite model for these systems as accreting sources surrounded by star-forming activity. The narrow-line LINERs appear to be the weaker counterparts of the Type 1 LINERs, where the low accretion rates cause the disappearance of the broad-line component. The enhanced sensitivity of the HST observations reveals a 30% increase in the incidence of accretion-powered systems at z ≈ 0. A comparison of the strength of the broad-line emission detected at different epochs implies potential broad-line variability on a decade-long timescale, with at least a factor of three in amplitude.« less

Inverse Compton X-Ray Halos Around High-z Radio Galaxies: A Feedback Mechanism Powered by Far-Infrared Starbursts or the Cosmic Microwave Background?

NASA Technical Reports Server (NTRS)

Small, Ian; Blundell, Katherine M.; Lehmer, B. D.; Alexander, D. M.

2012-01-01

We report the detection of extended X-ray emission around two powerful radio galaxies at z approx. 3.6 (4C 03.24 and 4C 19.71) and use these to investigate the origin of extended, inverse Compton (IC) powered X-ray halos at high redshifts. The halos have X-ray luminosities of L(sub X) approx. 3 x 10(exp 44) erg/s and sizes of approx.60 kpc. Their morphologies are broadly similar to the approx.60 kpc long radio lobes around these galaxies suggesting they are formed from IC scattering by relativistic electrons in the radio lobes, of either cosmic microwave background (CMB) photons or far-infrared photons from the dust-obscured starbursts in these galaxies. These observations double the number of z > 3 radio galaxies with X-ray-detected IC halos. We compare the IC X-ray-to-radio luminosity ratios for the two new detections to the two previously detected z approx. 3.8 radio galaxies. Given the similar redshifts, we would expect comparable X-ray IC luminosities if millimeter photons from the CMB are the dominant seed field for the IC emission (assuming all four galaxies have similar ages and jet powers). Instead we see that the two z approx. 3.6 radio galaxies, which are 4 fainter in the far-infrared than those at z 3.8, also have approx.4x fainter X-ray IC emission. Including data for a further six z > or approx. 2 radio sources with detected IC X-ray halos from the literature, we suggest that in the more compact, majority of radio sources, those with lobe sizes < or approx.100-200 kpc, the bulk of the IC emission may be driven by scattering of locally produced far-infrared photons from luminous, dust-obscured starbursts within these galaxies, rather than millimeter photons from the CMB. The resulting X-ray emission appears sufficient to ionize the gas on approx.100-200 kpc scales around these systems and thus helps form the extended, kinematically quiescent Ly(alpha) emission line halos found around some of these systems. The starburst and active galactic nucleus activity in these galaxies are thus combining to produce an even more effective and widespread "feedback" process, acting on the long-term gas reservoir for the galaxy, than either individually could achieve. If episodic radio activity and co-eval starbursts are common in massive, high-redshift galaxies, then this IC-feedback mechanism may play a role in affecting the star formation histories of the most massive galaxies at the present day.

Neopetrosiquinones A and B, Sesquiterpene Benzoquinones Isolated from the Deep-water Sponge Neopetrosia cf. proxima

PubMed Central

Winder, Priscilla L.; Baker, Heather L.; Linley, Patricia; Guzmán, Esther; Pomponi, Shirley A.; Diaz, M. Cristina; Reed, John K.; Wright, Amy E.

2011-01-01

Two new marine-derived sesquiterpene benzoquinones which we designate as neopetrosiquinone A (1) and B (2), have been isolated from a deep-water sponge of the family Petrosiidae. The structures were elucidated on the basis of their spectroscopic data. Compounds 1 and 2 inhibit the in vitro proliferation of the DLD-1 human colorectal adenocarcinoma cell line with IC50 values of 3.7 and 9.8 μM, respectively, and the PANC-1 human pancreatic carcinoma cell line with IC50 values of 6.1 and 13.8 μM, respectively. Neopetrosiquinone A (1) also inhibited the in vitro proliferation of the AsPC-1 human pancreatic carcinoma cell line with an IC50 value of 6.1 μM. The compounds are structurally related to alisiaquinone A, cyclozonarone and xestoquinone. PMID:22014756

Intravesical treatments of bladder pain syndrome/interstitial cystitis.

PubMed

Neuhaus, Jochen; Schwalenberg, Thilo

2012-12-01

Bladder pain syndrome/interstitial cystitis (BPS/IC) is a disabling chronic condition that affects up to 7% of women in the USA. In men, BPS/IC seems to be less common, but might be underestimated because it can be confused with chronic prostatitis. The aetiology and pathophysiology of BPS/IC are not well understood. Consequently, diagnosis and treatment is challenging and most therapies used to date are off-label. These therapies include bladder instillation with dimethyl sulfoxide (DMSO) and BCG, as well as hyperbaric oxygen therapy. Overall, botulinum neurotoxin A injection, intravesical sodium hyaluronate instillation and DMSO instillation seem to be the best-performing treatments, with response rates of 79%, 76% and 75%, respectively, and can be used effectively as second-line or third-line therapies for BPS/IC. However, additional high-quality randomized controlled trials are necessary to improve the available data.

NEAR-INFRARED SPECTROSCOPY OF THE TYPE IIn SN 2010jl: EVIDENCE FOR HIGH VELOCITY EJECTA

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

Borish, H. Jacob; Huang, Chenliang; Chevalier, Roger A.

2015-03-01

The Type IIn supernova SN 2010jl was relatively nearby and luminous, allowing detailed studies of the near-infrared (NIR) emission. We present 1-2.4 μm spectroscopy over the age range of 36-565 days from the earliest detection of the supernova. On day 36, the H lines show an unresolved narrow emission component along with a symmetric broad component that can be modeled as the result of electron scattering by a thermal distribution of electrons. Over the next hundreds of days, the broad components of the H lines shift to the blue by 700 km s{sup –1}, as is also observed in optical lines.more » The narrow lines do not show a shift, indicating they originate in a different region. He I λ10830 and λ20587 lines both show an asymmetric broad emission component, with a shoulder on the blue side that varies in prominence and velocity from –5500 km s{sup –1} on day 108 to –4000 km s{sup –1} on day 219. This component may be associated with the higher velocity flow indicated by X-ray observations of the supernova. The absence of the feature in the H lines suggests that this is from a He-rich ejecta flow. The He I λ10830 feature has a narrow P Cygni line, with absorption extending to ∼100 km s{sup –1} and strengthening over the first 200 days, and an emission component which weakens with time. At day 403, the continuum emission becomes dominated by a blackbody spectrum with a temperature of ∼1900 K, suggestive of dust emission.« less

Biotransformation of a potent anabolic steroid, mibolerone, with Cunninghamella blakesleeana, C. echinulata, and Macrophomina phaseolina, and biological activity evaluation of its metabolites.

PubMed

Siddiqui, Mahwish; Ahmad, Malik Shoaib; Wahab, Atia-Tul-; Yousuf, Sammer; Fatima, Narjis; Naveed Shaikh, Nimra; Rahman, Atta-Ur-; Choudhary, M Iqbal

2017-01-01

Seven metabolites were obtained from the microbial transformation of anabolic-androgenic steroid mibolerone (1) with Cunninghamella blakesleeana, C. echinulata, and Macrophomina phaseolina. Their structures were determined as 10β,17β-dihydroxy-7α,17α-dimethylestr-4-en-3-one (2), 6β,17β-dihydroxy-7α,17α-dimethylestr-4-en-3-one (3), 6β,10β,17β-trihydroxy-7α,17α-dimethylestr-4-en-3-one (4), 11β,17β-dihydroxy-(20-hydroxymethyl)-7α,17α-dimethylestr-4-en-3-one (5), 1α,17β-dihydroxy-7α,17α-dimethylestr-4-en-3-one (6), 1α,11β,17β-trihydroxy-7α,17α-dimethylestr-4-en-3-one (7), and 11β,17β-dihydroxy-7α,17α-dimethylestr-4-en-3-one (8), on the basis of spectroscopic studies. All metabolites, except 8, were identified as new compounds. This study indicates that C. blakesleeana, and C. echinulata are able to catalyze hydroxylation at allylic positions, while M. phaseolina can catalyze hydroxylation of CH2 and CH3 groups of substrate 1. Mibolerone (1) was found to be a moderate inhibitor of β-glucuronidase enzyme (IC50 = 42.98 ± 1.24 μM) during random biological screening, while its metabolites 2-4, and 8 were found to be inactive. Mibolerone (1) was also found to be significantly active against Leishmania major promastigotes (IC50 = 29.64 ± 0.88 μM). Its transformed products 3 (IC50 = 79.09 ± 0.06 μM), and 8 (IC50 = 70.09 ± 0.05 μM) showed a weak leishmanicidal activity, while 2 and 4 were found to be inactive. In addition, substrate 1 (IC50 = 35.7 ± 4.46 μM), and its metabolite 8 (IC50 = 34.16 ± 5.3 μM) exhibited potent cytotoxicity against HeLa cancer cell line (human cervical carcinoma). Metabolite 2 (IC50 = 46.5 ± 5.4 μM) also showed a significant cytotoxicity, while 3 (IC50 = 107.8 ± 4.0 μM) and 4 (IC50 = 152.5 ± 2.15 μM) showed weak cytotoxicity against HeLa cancer cell line. Compound 1 (IC50 = 46.3 ± 11.7 μM), and its transformed products 2 (IC50 = 43.3 ± 7.7 μM), 3 (IC50 = 65.6 ± 2.5 μM), and 4 (IC50 = 89.4 ± 2.7 μM) were also found to be moderately toxic to 3T3 cell line (mouse fibroblast). Interestingly, metabolite 8 showed no cytotoxicity against 3T3 cell line. Compounds 1-4, and 8 were also evaluated for inhibition of tyrosinase, carbonic anhydrase, and α-glucosidase enzymes, and all were found to be inactive.

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

Kuncarayakti, Hanindyo; Maeda, Keiichi; Doi, Mamoru

Integral field spectroscopy of 11 Type Ib/Ic supernova (SN Ib/Ic) explosion sites in nearby galaxies has been obtained using UH88/SNIFS and Gemini-N/GMOS. The use of integral field spectroscopy enables us to obtain both spatial and spectral information about the explosion site, enabling the identification of the parent stellar population of the SN progenitor star. The spectrum of the parent population provides metallicity determination via strong-line method and age estimation obtained via comparison with simple stellar population models. We adopt this information as the metallicity and age of the SN progenitor, under the assumption that it was coeval with the parentmore » stellar population. The age of the star corresponds to its lifetime, which in turn gives the estimate of its initial mass. With this method we were able to determine both the metallicity and initial (zero-age main sequence) mass of the progenitor stars of SNe Ib and Ic. We found that on average SN Ic explosion sites are more metal-rich and younger than SN Ib sites. The initial mass of the progenitors derived from parent stellar population age suggests that SN Ic has more massive progenitors than SN Ib. In addition, we also found indication that some of our SN progenitors are less massive than {approx}25 M{sub Sun }, indicating that they may have been stars in a close binary system that have lost their outer envelope via binary interactions to produce SNe Ib/Ic, instead of single Wolf-Rayet stars. These findings support the current suggestions that both binary and single progenitor channels are in effect in producing SNe Ib/Ic. This work also demonstrates the power of integral field spectroscopy in investigating SN environments and active star-forming regions.« less

Implementing New Non-Chromate Coatings Systems (Briefing Charts)

DTIC Science & Technology

2011-02-09

Initiate Cr6+ authorization process for continued Cr6+ use using the form, Authorization to Use Hexavalent Chromium. YES NO • Approval of...Aluminum and magnesium anodizing • Hard Chrome Plating • Type II conversion coating on aluminum alloys under chromated primer • Type II conversion coating...Elimination of Hexavalent Chromium 80% 5% 14% 1% Type II Type III Type IC Type IC Fatigue Critical 50% 50% Type II Type IC FRC-SE (JAX) Fully Integrated FRC

Cellular uptake and anticancer activity of carboxylated gallium corroles.

PubMed

Pribisko, Melanie; Palmer, Joshua; Grubbs, Robert H; Gray, Harry B; Termini, John; Lim, Punnajit

2016-04-19

We report derivatives of gallium(III) tris(pentafluorophenyl)corrole, 1 [Ga(tpfc)], with either sulfonic (2) or carboxylic acids (3, 4) as macrocyclic ring substituents: the aminocaproate derivative, 3 [Ga(ACtpfc)], demonstrated high cytotoxic activity against all NCI60 cell lines derived from nine tumor types and confirmed very high toxicity against melanoma cells, specifically the LOX IMVI and SK-MEL-28 cell lines. The toxicities of 1, 2, 3, and 4 [Ga(3-ctpfc)] toward prostate (DU-145), melanoma (SK-MEL-28), breast (MDA-MB-231), and ovarian (OVCAR-3) cancer cells revealed a dependence on the ring substituent: IC50values ranged from 4.8 to >200 µM; and they correlated with the rates of uptake, extent of intracellular accumulation, and lipophilicity. Carboxylated corroles 3 and 4, which exhibited about 10-fold lower IC50values (<20 µM) relative to previous analogs against all four cancer cell lines, displayed high efficacy (Emax= 0). Confocal fluorescence imaging revealed facile uptake of functionalized gallium corroles by all human cancer cells that followed the order: 4 > 3 > 2 > 1 (intracellular accumulation of gallium corroles was fastest in melanoma cells). We conclude that carboxylated gallium corroles are promising chemotherapeutics with the advantage that they also can be used for tumor imaging.

Cellular uptake and anticancer activity of carboxylated gallium corroles

PubMed Central

Pribisko, Melanie; Palmer, Joshua; Grubbs, Robert H.; Gray, Harry B.; Termini, John; Lim, Punnajit

2016-01-01

We report derivatives of gallium(III) tris(pentafluorophenyl)corrole, 1 [Ga(tpfc)], with either sulfonic (2) or carboxylic acids (3, 4) as macrocyclic ring substituents: the aminocaproate derivative, 3 [Ga(ACtpfc)], demonstrated high cytotoxic activity against all NCI60 cell lines derived from nine tumor types and confirmed very high toxicity against melanoma cells, specifically the LOX IMVI and SK-MEL-28 cell lines. The toxicities of 1, 2, 3, and 4 [Ga(3-ctpfc)] toward prostate (DU-145), melanoma (SK-MEL-28), breast (MDA-MB-231), and ovarian (OVCAR-3) cancer cells revealed a dependence on the ring substituent: IC50 values ranged from 4.8 to >200 µM; and they correlated with the rates of uptake, extent of intracellular accumulation, and lipophilicity. Carboxylated corroles 3 and 4, which exhibited about 10-fold lower IC50 values (<20 µM) relative to previous analogs against all four cancer cell lines, displayed high efficacy (Emax = 0). Confocal fluorescence imaging revealed facile uptake of functionalized gallium corroles by all human cancer cells that followed the order: 4 >> 3 > 2 >> 1 (intracellular accumulation of gallium corroles was fastest in melanoma cells). We conclude that carboxylated gallium corroles are promising chemotherapeutics with the advantage that they also can be used for tumor imaging. PMID:27044076

Polarization singularity indices in Gaussian laser beams

NASA Astrophysics Data System (ADS)

Freund, Isaac

2002-01-01

Two types of point singularities in the polarization of a paraxial Gaussian laser beam are discussed in detail. V-points, which are vector point singularities where the direction of the electric vector of a linearly polarized field becomes undefined, and C-points, which are elliptic point singularities where the ellipse orientations of elliptically polarized fields become undefined. Conventionally, V-points are characterized by the conserved integer valued Poincaré-Hopf index η, with generic value η=±1, while C-points are characterized by the conserved half-integer singularity index IC, with generic value IC=±1/2. Simple algorithms are given for generating V-points with arbitrary positive or negative integer indices, including zero, at arbitrary locations, and C-points with arbitrary positive or negative half-integer or integer indices, including zero, at arbitrary locations. Algorithms are also given for generating continuous lines of these singularities in the plane, V-lines and C-lines. V-points and C-points may be transformed one into another. A topological index based on directly measurable Stokes parameters is used to discuss this transformation. The evolution under propagation of V-points and C-points initially embedded in the beam waist is studied, as is the evolution of V-dipoles and C-dipoles.

Antiproliferative and Antibacterial Activities of Cirsium scabrum from Tunisia

PubMed Central

Sahli, Ramla; Dufloer, Cédric; Beaufay, Claire; Bero, Joanne; Ksouri, Riadh; Quetin-Leclercq, Joelle; Sahpaz, Sevser

2017-01-01

Several Cirsium species are known for their uses in traditional medicine and consequently are studied for their phytochemical content and their biological activities. In the framework of a previous study conducted on eight extremophile plants from Tunisia, we highlighted that the crude methanolic extract of C. scabrum, a not investigated thistle, showed moderate but quite selective cytotoxic activity against the cancerous cell line J774 compared to the noncancerous cell line WI38 (IC50 = 11.53 μg/ml on J774, IC50 = 29.89 µg/ml on WI38, and selectivity index = 2.6). In the current study, the partitions of the leaves of C. scabrum were analyzed for their antiproliferative activity on the same cell lines. From the most active petroleum ether partition, we isolated four triterpenoids including lupeol, taraxasterol acetate, and a (1 : 1) mixture of 25-hydroperoxycycloart-23-en-3β-ol and 24-hydroperoxycycloart-25-en-3β-ol. These two cycloartane-type triterpenoids are mostly responsible for this cytotoxic activity. On the other hand, the antimicrobial potential of this plant was also evaluated against 36 microorganisms. The moderate antibacterial activity against 6 Staphylococcus aureus and 2 Dermabacter hominis strains is mainly attributed to the butanol partition whose major compounds are glycosides of flavones. PMID:28785293

Antiproliferative and Antibacterial Activities of Cirsium scabrum from Tunisia.

PubMed

Sahli, Ramla; Rivière, Céline; Dufloer, Cédric; Beaufay, Claire; Neut, Christel; Bero, Joanne; Hennebelle, Thierry; Roumy, Vincent; Ksouri, Riadh; Quetin-Leclercq, Joelle; Sahpaz, Sevser

2017-01-01

Several Cirsium species are known for their uses in traditional medicine and consequently are studied for their phytochemical content and their biological activities. In the framework of a previous study conducted on eight extremophile plants from Tunisia, we highlighted that the crude methanolic extract of C. scabrum , a not investigated thistle, showed moderate but quite selective cytotoxic activity against the cancerous cell line J774 compared to the noncancerous cell line WI38 (IC 50 = 11.53  μ g/ml on J774, IC 50 = 29.89  µ g/ml on WI38, and selectivity index = 2.6). In the current study, the partitions of the leaves of C. scabrum were analyzed for their antiproliferative activity on the same cell lines. From the most active petroleum ether partition, we isolated four triterpenoids including lupeol, taraxasterol acetate, and a (1 : 1) mixture of 25-hydroperoxycycloart-23-en-3 β -ol and 24-hydroperoxycycloart-25-en-3 β -ol. These two cycloartane-type triterpenoids are mostly responsible for this cytotoxic activity. On the other hand, the antimicrobial potential of this plant was also evaluated against 36 microorganisms. The moderate antibacterial activity against 6 Staphylococcus aureus and 2 Dermabacter hominis strains is mainly attributed to the butanol partition whose major compounds are glycosides of flavones.

Integrated circuit failure analysis by low-energy charge-induced voltage alteration

DOEpatents

Cole, E.I. Jr.

1996-06-04

A scanning electron microscope apparatus and method are described for detecting and imaging open-circuit defects in an integrated circuit (IC). The invention uses a low-energy high-current focused electron beam that is scanned over a device surface of the IC to generate a charge-induced voltage alteration (CIVA) signal at the location of any open-circuit defects. The low-energy CIVA signal may be used to generate an image of the IC showing the location of any open-circuit defects. A low electron beam energy is used to prevent electrical breakdown in any passivation layers in the IC and to minimize radiation damage to the IC. The invention has uses for IC failure analysis, for production-line inspection of ICs, and for qualification of ICs. 5 figs.

Integrated circuit failure analysis by low-energy charge-induced voltage alteration

DOEpatents

Cole, Jr., Edward I.

1996-01-01

A scanning electron microscope apparatus and method are described for detecting and imaging open-circuit defects in an integrated circuit (IC). The invention uses a low-energy high-current focused electron beam that is scanned over a device surface of the IC to generate a charge-induced voltage alteration (CIVA) signal at the location of any open-circuit defects. The low-energy CIVA signal may be used to generate an image of the IC showing the location of any open-circuit defects. A low electron beam energy is used to prevent electrical breakdown in any passivation layers in the IC and to minimize radiation damage to the IC. The invention has uses for IC failure analysis, for production-line inspection of ICs, and for qualification of ICs.

On the Distance Measurements toward Young Milky Way Objects. I. Study of IC 2944

NASA Astrophysics Data System (ADS)

Krełowski, J.; Strobel, A.; Godunova, V.; Bondar, A.

2017-12-01

We compare distances to a very young stellar aggregate, IC 2944, using three methods: direct parallaxes of Gaia, spectrophotometric parallax and our method based on intensities of interstellar CaII lines. The discrepancies between spectrophotometric distances and those, based on CaII K and H lines, were already reported. The interstellar CaII H and K lines allow one to determine both distances and radial velocities of the intervening clouds. Thus, these data allow us to check the aggregate membership. It is also possible to check the spectral classification of considered targets which is necessary for spectrophotometric parallaxes. Using three methods, we determined distances to IC 2944 stars. We demonstrate that CaII based distances agree very well with the kinematic ones but are generally much smaller than the spectrophotometric ones. We conclude that the majority of IC 2944 objects is obscured by clouds producing neutral ("gray") extinction which diminishes their brightness exactly like extended distances. This influences spectrophotometric parallaxes while those, based on the CaII lines, do not depend on extinction and this method seems to be the most reliable one inside the thin disk of our Galaxy. The Gaia trigonometric parallaxes lead to distances similar to those obtained using the CaII method if their errors are reasonably small.

Quantification of sensitivity and resistance of breast cancer cell lines to anti-cancer drugs using GR metrics

PubMed Central

Hafner, Marc; Heiser, Laura M.; Williams, Elizabeth H.; Niepel, Mario; Wang, Nicholas J.; Korkola, James E.; Gray, Joe W.; Sorger, Peter K.

2017-01-01

Traditional means for scoring the effects of anti-cancer drugs on the growth and survival of cell lines is based on relative cell number in drug-treated and control samples and is seriously confounded by unequal division rates arising from natural biological variation and differences in culture conditions. This problem can be overcome by computing drug sensitivity on a per-division basis. The normalized growth rate inhibition (GR) approach yields per-division metrics for drug potency (GR50) and efficacy (GRmax) that are analogous to the more familiar IC50 and Emax values. In this work, we report GR-based, proliferation-corrected, drug sensitivity metrics for ~4,700 pairs of breast cancer cell lines and perturbagens. Such data are broadly useful in understanding the molecular basis of therapeutic response and resistance. Here, we use them to investigate the relationship between different measures of drug sensitivity and conclude that drug potency and efficacy exhibit high variation that is only weakly correlated. To facilitate further use of these data, computed GR curves and metrics can be browsed interactively at http://www.GRbrowser.org/. PMID:29112189

Effect of capping agents on the cytotoxicity of silver nanoparticles in human normal and cancer skin cell lines

NASA Astrophysics Data System (ADS)

Netchareonsirisuk, Ponsawan; Puthong, Songchan; Dubas, Stephan; Palaga, Tanapat; Komolpis, Kittinan

2016-11-01

Silver nanoparticles (AgNPs) are among the most widely used nanomaterials in medical and consumer products. However, safety in the uses of AgNPs is still controversial. The toxicity of AgNPs toward various cell types has been reported to depend on the surface properties of the nanoparticles. In this study, the effect of AgNPs with the average size of 5-15 nm on the viability of the CCD-986SK human normal skin fibroblast cell line and A375 human malignant melanoma cell line was evaluated. Comparative toxicity studies, based on MTT assay, were performed by using either sodium alginate or poly (4-styrenesulfonic acid-co-maleic acid) sodium salt (PSSMA) as capping agent in the nanoparticle preparation. The cytotoxicity tests revealed that AgNO3 alone was highly toxic to both cell types while both alginate and PSSMA alone were not toxic. AgNPs capped with alginate were selectively toxic to the cancer cell line but not to the normal cell line while AgNPs capped with PSSMA were toxic to both cancer and normal cell lines. Judging from the 50 % inhibition concentration (IC50), it was found that the cancer cell line was more sensitive to AgNPs than the normal cell line. Study on the mode of cell death by annexin V and propidium iodide staining revealed that AgNPs induced more apoptotic cell death (84-90 %) than necrosis (8-12 %) in the skin cancer cell line. These results suggest that the toxicity of AgNPs depended on the type of capping agent and the type of cell line.

Capillary Flow of Liquid Metals in Brazing

NASA Astrophysics Data System (ADS)

Dehsara, Mohammad

Capillary flow is driven or controlled by capillary forces, exerted at the triple line where the fluid phases meet the solid boundary. Phase field (PF) models naturally accommodate diffusive triple line motion with variable contact angle, thus allowing for the no-slip boundary condition without the stress singularities. Moreover, they are uniquely suited for modeling of topological discontinuities which often arise during capillary flows. In this study, we consider diffusive triple line motion within two PF models: the compositionally compressible (CC) and the incompressible (IC) models. We derive the IC model as a systematic approximation to the CC model, based on a suitable choice of continuum velocity field. The CC model, applied to the fluids of dissimilar mass densities, exhibits a computational instability at the triple line. The IC model perfectly represents the analytic equilibria. We develop the parameter identification procedure and show that the triple line kinetics can be well represented by the IC model's diffusive boundary condition. The IC model is first tested by benchmarking the phase-field and experimental kinetics of water, and silicone oil spreading over the glass plates in which two systems do not interact with the substrate. Then, two high-temperature physical settings involving spreading of the molten Al-Si alloy: one over a rough wetting substrate, the other over a non-wetting substrate are modeled in a T-joint structure which is a typical geometric configuration for many brazing and soldering applications. Surface roughness directly influences the spreading of the molten metal by causing break-ups of the liquid film and trapping the liquid away from the joint. In the early stages of capillary flow over non-wetting surface, the melting and flow are concurrent, so that the kinetics of wetting is strongly affected by the variations in effective viscosity of the partially molten metal. We define adequate time-dependent functions for the variations of Al-Si alloy viscosity and triple line mobility to describe the wetting kinetics.

Synergistic effect of sevoflurane and isoflurane on inhibition of the adult-type muscle nicotinic acetylcholine receptor by rocuronium.

PubMed

Liu, Li; Li, Wei; Wei, Ke; Cao, Jun; Luo, Jie; Wang, Bin; Min, Su

2013-06-01

Inhaled anesthetics increase the incidence of postoperative residual neuromuscular blockade, and the mechanism is still unclear. We have investigated the synergistic effect of low-concentration inhaled anesthetics and rocuronium on inhibition of the inward current of the adult-type muscle nicotinic acetylcholine receptor (ε-nAChR). Adult-type mouse muscle ε-nAChR was expressed in HEK293 cells by liposome transfection. The inward current of the ε-nAChR was activated by use of 10 μmol/L acetylcholine alone or in combination with different concentrations of sevoflurane, isoflurane, or rocuronium. The concentration-response curves of five cells were constructed, and the data yielded the 5, 25, and 50 % inhibitory concentrations (IC5, IC25, and IC50, respectively) for single-drug application. Subsequently, the functional channels were perfused by adding 0.5 IC5 of either sevoflurane or isoflurane (aqueous concentrations 140 and 100 μmol/L, respectively) to the solution, followed by addition of IC5, IC25, or IC50 rocuronium. The amount of inhibition was calculated to quantify their synergistic effect. The inhibitory effect of rocuronium was enhanced by sevoflurane or isoflurane in a concentration-dependent manner. Sevoflurane or isoflurane (0.5 IC5) with rocuronium at IC5, IC25, and IC50 synergistically inhibited the current amplitude of adult-type muscle ε-nAChR. When the IC5 of rocuronium was used, isoflurane had a stronger synergistic effect than sevoflurane (p < 0.05). When rocuronium was applied at higher concentrations (IC25 and IC50), sevoflurane had an effect similar to that of isoflurane. For both inhaled anesthetics, the synergistic effect was more intense for rocuronium at IC5 than for rocuronium at IC25 or IC50. Residual-concentration sevoflurane or isoflurane has a strong synergistic effect with rocuronium at clinically relevant residual concentrations. A lower rocuronium concentration resulted in a stronger synergistic effect.

Collision-induced stimulated photon echo generated at transition 0-1 on broad spectral line conditions

NASA Astrophysics Data System (ADS)

Rubtsova, N. N.; Gol'dort, V. G.; Ishchenko, V. N.; Khvorostov, E. B.; Kochubei, S. A.; Borisov, G. M.; Ledovskikh, D. V.; Reshetov, V. A.

2018-04-01

For the first time, the collision induced stimulated photon echo generated at transition 1S0 → 3 P1 of 174Yb (type 0-1) in the mixture of gases Yb  +  Xe was investigated in the presence of weak longitudinal magnetic field, with experimental parameters corresponding to broad spectral line conditions. Comparison of the experimental echo amplitude versus magnetic field strength dependence with the theoretical curve shows a very good agreement, giving rise to an improved estimate for the difference between alignment and orientation decay rates.

X-Ray Absorbed, Broad-Lined, Red AGN and the Cosmic X-Ray Background

NASA Technical Reports Server (NTRS)

Mushotzky, Richard (Technical Monitor); Wilkes, Belinda

2005-01-01

We have obtained XMM spectra for five red, 2MASS AGN, selected from a sample observed by Chandra to be X-ray bright and to cover a range of hardness ratios. Our results confirm the presence of substantial absorbing material in three sources which have optical classifications ranging from Type 1 to Type 2, with an intrinsically flat (hard) power law continuum indicated in the other two. The presence of both X-ray absorption and broad optical emission lines with the usual strength suggests either a small (nuclear) absorber or a favored viewing angle so as to cover the X-ray source but not the broad emission line region (BELR). A soft excess is detected in all three Type 1 sources. We speculate that this soft X-ray emission may arise in an extended region of ionized gas, perhaps linked with the polarized (scattered) light which is a feature of these sources. The spectral complexity revealed by XMM emphasizes the limitations of the low S/N Chandra data. Overall, the new XMM results strengthen our conclusions (Wilkes et al. 2002) that the observed X-ray continua of red AGN are unusually hard at energies greater than 2 keV. Whether due to substantial line-of-sight absorption or to an intrinsically hard or reflection-dominated spectrum, these 'red' AGN have an observed spectral form consistent with contributing significantly to the missing had absorbed population of the Cosmic X-ray Background (CXRB). When absorption and or reflection is taken into account, all these AGN have power law slopes typical of broad-line (Type 1) AGN (Gamma approximately 1.9). This appears to resolve the spectral paradox which for so long has existed between the CXRB and the AGN thought to be the dominant contributors. It also suggests two scenarios whereby Type 1 AGN/QSOs may be responsible for a significant fraction of the CXRB at energies above 2 keV: 1) X-ray absorbed AGN/QSOs with visible broad emission lines; 2) AGN/QSOs with complex spectra whose hardness greater than 2 keV is not detectable in the typically low S/N data of X-ray surveys. Even if absorption is present in only half of the population, the large number of 'red' AGN suggests a development of unification models, where the continuum source is surrounded, over a substantial solid angle, by the wind or atmosphere of an accretion disk/torus. X-ray observations of such AGN not only provide a check on the presence of absorption, but also a unique probe of the absorbing material. Improved information on their space density, in particular as a function of redshift, will soon be provided by Spitzer-Chandra wide area surveys, allowing better estimates of both the importance of red AGN to the full AGN population and their contribution to the CXRB.

Sesquiterpenoids from the cultured mycelia of Ganoderma capense.

PubMed

Tan, Zhen; Zhao, Jinlian; Liu, Jimei; Zhang, Min; Chen, Ridao; Xie, Kebo; Dai, Jungui

2017-04-01

Eleven new sesquiterpenoids, including eight cadinane-type sesquiterpenoids, Ganodermanol A-H (1-8), and three eudesmane-type sesquiterpenoids, Ganodermanol I-K (9-11), together with three known compounds (12-14), were isolated from the cultured mycelia of Ganoderma capense. Their structures and absolute configurations were identified through combined extensive spectroscopic analysis, circular dichroism (CD), and Mo 2 (AcO) 4 -induced CD. Compounds 4 and 9 exhibited moderate cytotoxic activity against the human cancer cell line HCT116 with IC 50 values of 16.6 and 12.2μM, respectively. Copyright © 2017 Elsevier B.V. All rights reserved.

Novel 1, 4-dihydropyridines for L-type calcium channel as antagonists for cadmium toxicity

PubMed Central

Saddala, Madhu Sudhana; Kandimalla, Ramesh; Adi, Pradeepkiran Jangampalli; Bhashyam, Sainath Sri; Asupatri, Usha Rani

2017-01-01

The present study, we design and synthesize the novel dihydropyridine derivatives, i.e., 3 (a-e) and 5 (a-e) and evaluated, anticonvulsant activity. Initially due to the lacuna of LCC, we modeled the protein through modeller 9.15v and evaluated through servers. Docking studies were performed with the synthesized compounds and resulted two best compounds, i.e., 5a, 5e showed the best binding energies. The activity of intracellular Ca2+ measurements was performed on two cell lines: A7r5 (rat aortic smooth muscle cells) and SH-SY5Y (human neuroblastoma cells). The 5a and 5e compounds was showing the more specific activity on L-type calcium channels, i.e. A7r5 (IC50 = 0.18 ± 0.02 and 0.25 ± 0.63 μg/ml, respectively) (containing only L-type channels) than SH-SY5Y (i.e. both L-type and T-type channels) (IC50 = 8 ± 0.23 and 10 ± 0.18 μg/ml, respectively) with intracellular calcium mobility similar to amlodipine. Finally, both in silico and in vitro results exploring two derivatives 5a and 5e succeeded to treat cadmium toxicity. PMID:28345598

Identification of SDSS J141324.27+530527.0 as a New “Changing-look” Quasar with a “Turn-on” Transition

NASA Astrophysics Data System (ADS)

Wang, J.; Xu, D. W.; Wei, J. Y.

2018-05-01

We report an identification of SDSS J141324+530527.0 (SBS 1411+533) at z = 0.456344 as a new “changing-look” quasar with a “turn-on” spectral type transition from Type-1.9/2 to Type-1 within a rest-frame timescale of 1–10 yr by a comparison of our new spectroscopic observation and the Sloan Digital Sky Survey (SDSS) archive database. The SDSS DR7 spectrum taken in 2003 is dominated by a starlight emission from host galaxy redward of the Balmer limit, and has a non-detectable broad Hβ line. The new spectrum taken by us on 2017 June 1 and the SDSS DR14 spectrum taken on 2017 May 29 indicate that the object has a typical quasar spectrum with a blue continuum and strong Balmer broad emission lines. In addition, an intermediate spectral type can be identified in the SDSS DR13 spectrum taken in 2015. The invariability of the line wing of Mg II λ2800 emission and timescale argument (the invariability of [O III]λ5007 line blue asymmetry) suggests that a variation of obscuration (an accelerating outflow) is not a favorable scenario. The timescale argument allows us to believe the type transition is possibly caused by either a viscous radial inflow or a disk instability around a ∼ (5{--}9)× {10}7 {M}ȯ black hole.

Synthesis and QSAR study of novel α-methylene-γ-butyrolactone derivatives as antifungal agents.

PubMed

Wu, Yong-Ling; Wang, De-Long; Guo, En-Hui; Song, Shuang; Feng, Jun-Tao; Zhang, Xing

2017-03-01

Thirty-six new α-benzylidene-γ-lactone compounds based α-methylene-γ-butyrolactone substructure were prepared and characterized by spectroscopic analysis. All compounds were evaluated for antifungal activities in vitro against six plant pathogenic fungi and the half maximal inhibitory concentration (IC 50 ) against Botrytis cinerea and Colletotrichum lagenarium were investigated. Compounds 5c-3 and 5c-5 with the halogen atom exhibited excellent fungicidal activity against B. cinerea (IC 50 =22.91, 18.89μM). The structure-activity relationships (SARs) analysis indicated that the derivatives with electron-withdrawing substituents at the meta- or para-positions improves the activity. Via the heuristic method, the generated quantitative structure-activity relationship (QSAR) model (R 2 =0.961) revealed a strong correlation of antifungal activity against B. cinerea with molecular structures of these compounds. Meanwhile, the cytotoxicity of 20 representative derivatives was tested in the human tumor cells line (HepG2) and the hepatic L02 cells line, the result indicated that the synthesized compounds showed significant inhibitory activity and limited selectivity. Compound 5c-5 has the highest fungicidal activity with IC 50 =18.89μM (against B. cinerea.) but low cytotoxicity with IC 50 =35.4μM (against HepG2 cell line) and IC 50 =68.8μM (against Hepatic L02 cell line). These encouraging results can be providing an alternative, promising use of α-benzylidene-γ-lactone through the design and exploration of eco-friendly fungicides with low toxicity and high efficiency. Copyright © 2017 Elsevier Ltd. All rights reserved.

Highly Accreting Quasars at High Redshift

NASA Astrophysics Data System (ADS)

Martínez-Aldama, Mary L.; Del Olmo, Ascensión; Marziani, Paola; Sulentic, Jack W.; Negrete, C. Alenka; Dultzin, Deborah; Perea, Jaime; D'Onofrio, Mauro

2017-12-01

We present preliminary results of a spectroscopic analysis for a sample of type 1 highly accreting quasars (LLedd>0.2) at high redshift, z 2-3. The quasars were observed with the OSIRIS spectrograph on the GTC 10.4 m telescope located at the Observatorio del Roque de los Muchachos in La Palma. The highly accreting quasars were identified using the 4D Eigenvector 1 formalism, which is able to organize type 1 quasars over a broad range of redshift and luminosity. The kinematic and physical properties of the broad line region have been derived by fitting the profiles of strong UV emission lines such as AlIII, SiIII and CIII. The majority of our sources show strong blueshifts in the high-ionization lines and high Eddington ratios which are related with the productions of outflows. The importance of highly accreting quasars goes beyond a detailed understanding of their physics: their extreme Eddington ratio makes them candidates standard candles for cosmological studies.

CO-SPATIAL LONG-SLIT UV/OPTIC AL SPECTRA OF 10 GALACTIC PLANETARY NEBULAE WITH HST/STIS. I. DESCRIPTION OF THE OBSERVATIONS, GLOBAL EMISSION-LINE MEASUREMENTS, AND CNO ABUNDANCES

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

Dufour, Reginald J.; Kwitter, Karen B.; Shaw, Richard A.

We present observations and initial analysis from a Hubble Space Telescope (HST) Cycle 19 program using STIS to obtain the first co-spatial, UV–optical spectra of 10 Galactic planetary nebulae (PNs). Our primary objective was to measure the critical emission lines of carbon and nitrogen with unprecedented signal-to-noise ratio (S/N) and spatial resolution over the wavelength range 1150–10270 Å, with the ultimate goal of quantifying the production of these elements in low- and intermediate-mass stars. Our sample was selected from PNs with a near-solar metallicity, but spanning a broad range in N/O based on published ground-based and IUE spectra. This study,more » the first of a series, concentrates on the observations and emission-line measurements obtained by integrating along the entire spatial extent of the slit. We derived ionic and total elemental abundances for the seven PNs with the strongest UV line detections (IC 2165, IC 3568, NGC 2440, NGC 3242, NGC 5315, NGC 5882, and NGC 7662). We compare these new results with other recent studies of the nebulae and discuss the relative merits of deriving the total elemental abundances of C, N, and O using ionization correction factors (ICFs) versus summed abundances. For the seven PNs with the best UV line detections, we conclude that summed abundances from direct diagnostics of ions with measurable UV lines give the most accurate values for the total elemental abundances of C and N (although ICF abundances often produced good results for C). In some cases where significant discrepancies exist between our abundances and those from other studies, we show that the differences can often be attributed to their use of fluxes that are not co-spatial. Finally, we examined C/O and N/O versus O/H and He/H in well-observed Galactic, LMC, and SMC PNs and found that highly accurate abundances are essential for properly inferring elemental yields from their progenitor stars. Future papers will discuss photoionization modeling of our observations, of both the integrated spectra and spatial variations of the UV versus optical lines along the STIS slit lengths, which are unique to our observations.« less

SN 2013dx associated with GRB 130702A: a detailed photometric and spectroscopic monitoring and a study of the environment

NASA Astrophysics Data System (ADS)

D'Elia, V.; Pian, E.; Melandri, A.; D'Avanzo, P.; Della Valle, M.; Mazzali, P. A.; Piranomonte, S.; Tagliaferri, G.; Antonelli, L. A.; Bufano, F.; Covino, S.; Fugazza, D.; Malesani, D.; Møller, P.; Palazzi, E.

2015-05-01

Aims: Long-duration gamma-ray bursts (GRBs) and broad-line, type Ic supernovae (SNe) are strongly connected. We aim at characterizing SN 2013dx, which is associated with GRB 130702A, through a sensitive and extensive ground-based observational campaign in the optical-IR band. Methods: We monitored the field of the Swift GRB 130702A (redshift z = 0.145) using the 8.2 m VLT, the 3.6 m TNG and the 0.6 m REM telescopes during the time interval between 4 and 40 days after the burst. Photometric and spectroscopic observations revealed the associated type Ic SN 2013dx. Our multiband photometry allowed constructing a bolometric light curve. Results: The bolometric light curve of SN 2013dx resembles that of 2003dh (associated with GRB 030329), but is ~10% faster and ~25% dimmer. From this we infer a synthesized 56Ni mass of ~0.2 M⊙. The multi-epoch optical spectroscopy shows that the SN 2013dx behavior is best matched by SN 1998bw, among the other well-known low-redshift SNe associated with GRBs and XRFs, and by SN 2010ah, an energetic type Ic SN not associated with any GRB. The photospheric velocity of the ejected material declines from ~2.7 × 104 km s-1 at 8 rest frame days from the explosion, to ~3.5 × 103 km s-1 at 40 days. These values are extremely close to those of SN1998bw and 2010ah. We deduce for SN 2013dx a kinetic energy of ~35 × 1051 erg and an ejected mass of ~7 M⊙. This suggests that the progenitor of SN2013dx had a mass of ~25-30 M⊙, which is 15-20% less massive than that of SN 1998bw. Finally, we studied the SN 2013dx environment through spectroscopy of the closeby galaxies: 9 out of the 14 inspected galaxies lie within 0.03 in redshift from z = 0.145, indicating that the host of GRB 130702A/SN 2013dx belongs to a group of galaxies, an unprecedented finding for a GRB-associated SN and, to our knowledge, for long GRBs in general. Based on observations collected at the Italian 3.6-m Telescopio Nazionale Galileo (TNG), operated on the island of La Palma by the Fundacion Galileo Galilei of the INAF (Instituto Nazionale di Astrofisica) at the Spanish Observatorio del Roque de los Muchachos of the Instituto de Astrofisica de Canarias under program A27TAC 5, and at the European Southern Observatory, ESO, the VLT/Antu telescope, Paranal, Chile, proposal code: 291.D-5032(A).Appendix A is available in electronic form at http://www.aanda.org

Integral field spectroscopy of H II regions in M33

NASA Astrophysics Data System (ADS)

López-Hernández, Jesús; Terlevich, Elena; Terlevich, Roberto; Rosa-González, Daniel; Díaz, Ángeles; García-Benito, Rubén; Vílchez, José; Hägele, Guillermo

2013-03-01

Integral field spectroscopy is presented for star-forming regions in M33. A central area of 300 × 500 pc2 and the external H II region IC 132, at a galactocentric distance ˜19 arcmin (4.69 kpc), were observed with the Potsdam Multi-Aperture Spectrophotometer instrument at the 3.5-m telescope of the Centro Astronómico Hispano-Alemán (CAHA, aka Calar Alto Observatory). The spectral coverage goes from 3600 Å to 1 μm to include from [O II] λ3727 Å to the near-infrared lines required for deriving sulphur electron temperature and abundance diagnostics. Local conditions within individual H II regions are presented in the form of emission-line fluxes and physical conditions for each spatial resolution element (spaxel) and for segments with similar Hα surface brightness. A clear dichotomy is observed when comparing the central to outer disc H II regions. While the external H II region has higher electron temperature plus larger Hβ equivalent width, size and excitation, the central region has higher extinction and metal content. The dichotomy extends to the Baldwin-Phillips-Terlevich (BPT) diagnostic diagrams that show two orthogonal broad distributions of points. By comparing with pseudo-3D photoionization models, we conclude that the bulk of observed differences are probably related to a different ionization parameter and metallicity. Wolf-Rayet (WR) features are detected in IC 132, and resolved into two concentrations whose integrated spectra were used to estimate the characteristic number of WR stars. No WR features were detected in the central H II regions despite their higher metallicity.

Ganoboninketals A-C, Antiplasmodial 3,4-seco-27-Norlanostane Triterpenes from Ganoderma boninense Pat.

PubMed

Ma, Ke; Ren, Jinwei; Han, Junjie; Bao, Li; Li, Li; Yao, Yijian; Sun, Chen; Zhou, Bing; Liu, Hongwei

2014-08-22

Three new nortriterpenes, ganoboninketals A-C (1-3), featuring rearranged 3,4-seco-27-norlanostane skeletons and highly complex polycyclic systems were isolated from the medicinal mushroom Ganoderma boninense. The structures of the new metabolites were established by spectroscopic methods. The absolute configurations in 1-3 were assigned by electronic circular dichroism (ECD) calculations. Compounds 1-3 showed antiplasmodial activity against Plasmodium falciparum with IC50 values of 4.0, 7.9, and 1.7 μM, respectively. Compounds 1 and 3 also displayed weak cytotoxicity against A549 cell line with IC50 values of 47.6 and 35.8 μM, respectively. Compound 2 showed weak cytotoxicity toward HeLa cell line with an IC50 value of 65.5 μM. Compounds 1-3 also presented NO inhibitory activity in the LPS-induced macrophages with IC50 values of 98.3, 24.3, and 60.9 μM, respectively.

Extremely red quasars from SDSS, BOSS and WISE: classification of optical spectra

NASA Astrophysics Data System (ADS)

Ross, Nicholas P.; Hamann, Fred; Zakamska, Nadia L.; Richards, Gordon T.; Villforth, Carolin; Strauss, Michael A.; Greene, Jenny E.; Alexandroff, Rachael; Brandt, W. Niel; Liu, Guilin; Myers, Adam D.; Pâris, Isabelle; Schneider, Donald P.

2015-11-01

Quasars with extremely red infrared-to-optical colours are an interesting population that can test ideas about quasar evolution as well as orientation, obscuration and geometric effects in the so-called AGN unified model. To identify such a population, we match the quasar catalogues of the Sloan Digital Sky Survey (SDSS), the Baryon Oscillation Spectroscopic Survey (BOSS) to the Wide-Field Infrared Survey Explorer (WISE) to identify quasars with extremely high infrared-to-optical ratios. We identify 65 objects with rAB - W4Vega > 14 mag (i.e. Fν(22 μm)/Fν(r) ≳ 1000). This sample spans a redshift range of 0.28 < z < 4.36 and has a bimodal distribution, with peaks at z ˜ 0.8 and z ˜ 2.5. It includes three z > 2.6 objects that are detected in the W4 band but not W1 or W2 (i.e. `W1W2 dropouts'). The SDSS/BOSS spectra show that the majority of the objects are reddened type 1 quasars, type 2 quasars (both at low and high redshift) or objects with deep low-ionization broad absorption lines (BALs) that suppress the observed r-band flux. In addition, we identify a class of type 1 permitted broad emission-line objects at z ≃ 2-3 which are characterized by emission line rest-frame equivalent widths (REWs) of ≳150 Å, much larger than those of typical quasars. In particular, 55 per cent (45 per cent) of the non-BAL type 1s with measurable C IV in our sample have REW(C IV) > 100 (150) Å, compared to only 5.8 per cent (1.3 per cent) for non-BAL quasars in BOSS. These objects often also have unusual line ratios, such as very high N V/Ly α ratios. These large REWs might be caused by suppressed continuum emission analogous to type 2 quasars; however, there is no obvious mechanism in standard unified models to suppress the continuum without also obscuring the broad emission lines.

Neopetrosiquinones A and B, sesquiterpene benzoquinones isolated from the deep-water sponge Neopetrosia cf. proxima.

PubMed

Winder, Priscilla L; Baker, Heather L; Linley, Patricia; Guzmán, Esther A; Pomponi, Shirley A; Diaz, M Cristina; Reed, John K; Wright, Amy E

2011-11-15

Two new marine-derived sesquiterpene benzoquinones which we designate as neopetrosiquinones A (1) and B (2), have been isolated from a deep-water sponge of the family Petrosiidae. The structures were elucidated on the basis of their spectroscopic data. Compounds 1 and 2 inhibit the in vitro proliferation of the DLD-1 human colorectal adenocarcinoma cell line with IC(50) values of 3.7 and 9.8 μM, respectively, and the PANC-1 human pancreatic carcinoma cell line with IC(50) values of 6.1 and 13.8 μM, respectively. Neopetrosiquinone A (1) also inhibited the in vitro proliferation of the AsPC-1 human pancreatic carcinoma cell line with an IC(50) value of 6.1 μM. The compounds are structurally related to alisiaquinone A, cyclozonarone, and xestoquinone. Copyright © 2011 Elsevier Ltd. All rights reserved.

Doxorubicin-anti-carcinoembryonic antigen immunoconjugate activity in vitro.

PubMed

Richardson, V J; Ford, C H; Tsaltas, G; Gallant, M E

1989-04-01

An in vitro model consisting of a series of 11 human cancer cell lines with varying density of expression of membrane carcinoembryonic antigen (CEA) has been used to evaluate conjugates of doxorubicin (Adriamycin) covalently linked by a carbodiimide method to goat polyclonal antibodies and mouse monoclonal antibodies to CEA. Conjugates were produced which retained both antigen binding and drug cytotoxicity. IC50 values were determined for free drug, free drug mixed with unconjugated antibodies and for the immunoconjugates. Cell lines that were very sensitive to free drug (IC50 less than 100 ng/ml) were also found to be highly sensitive to conjugated drug and similarly cell lines resistant to drug (IC50 greater than 1,000 ng/ml) were also resistant to conjugated drug. Although there was no correlation between CEA expression and conjugates efficacy, competitive inhibition studies using autologous antibody to block conjugate binding to cells indicated immunoconjugates specificity for the CEA target.

A VLT VIMOS study of the anomalous BCD Mrk996: mapping the ionized gas kinematics and abundances

NASA Astrophysics Data System (ADS)

James, B. L.; Tsamis, Y. G.; Barlow, M. J.; Westmoquette, M. S.; Walsh, J. R.; Cuisinier, F.; Exter, K. M.

2009-09-01

A study of the blue compact dwarf (BCD) galaxy Mrk996 based on high-resolution optical Very Large Telescope Visible Multi-Object Spectrograph integral field unit spectroscopy is presented. Mrk996 displays multicomponent line emission, with most line profiles consisting of a narrow, central Gaussian [full width at half-maximum (FWHM) ~ 110kms-1] with an underlying broad component (FWHM ~ 400kms-1). The broad HI Balmer component splits into two separate broad components inside a 1.5-arcsec radius from the nucleus; these are attributed to a two-armed minispiral. This spiral-like nucleus rotates in the same sense as the extended narrow line ionized gas but is offset by ~50kms-1 from the systemic velocity of the galaxy. The rotation curve of Mrk996 derived from the Hα narrow component yields a total mass of 5 × 108Msolar within a radius of 3kpc. From the Hα luminosity we infer a global star formation rate of ~2Msolaryr-1. The high excitation energy, high critical density [OIII] λ4363 and [NII] λ5755 lines are only detected from the inner region and exist purely in broad component form, implying unusual excitation conditions. Surface brightness, radial velocity and FWHM maps for several emission components are presented. A separate physical analysis of the broad and narrow emission line regions is undertaken. We derive an upper limit of 10000K for the electron temperature of the narrow line gas, together with an electron density of 170cm-3, typical of normal HII regions. For the broad line component, measured [OIII] and [FeIII] diagnostic line ratios are consistent with a temperature of 11000K and an electron density of 107cm-3. The broad line emission regions show N/H and N/O enrichment factors of ~20 relative to the narrow line regions, but no He/H, O/H, S/H or Ar/H enrichment is inferred. Previous studies indicated that Mrk996 showed anomalously high N/O ratios compared with BCDs of a similar metallicity. Our multicomponent analysis yields a revised metallicity of >=0.5Zsolar (12 + logO/H = 8.37) for both the narrow and broad gas components, significantly higher than previous studies. As a result the narrow line region's N/O ratio is now typical for the galaxy's metallicity. The narrow line component's N/O ratio peaks outside the core region, spatially correlating with ~3-Myr-old stellar populations. The dominant line excitation mechanism is photoionization by the ~3000 Wolf-Rayet stars and ~150000 O-type stars estimated to be present in the core. This is indeed a peculiar BCD, with extremely dense zones of gas in the core, through which stellar outflows and possible shock fronts permeate contributing to the excitation of the broad line emission. Based on observations made with ESO telescopes at the Paranal Observatory under programme ID 078.B-0353(A). E-mail: bj@star.ucl.ac.uk (BLJ); tsamis@iaa.es (YGT)

A Survey of X-Ray Variability in Seyfert 1 Galaxies with XMM-Newton to study the soft excess and the broad Fe lines

NASA Astrophysics Data System (ADS)

Ponti, Gabriele

The nature of the soft excess and the presence of the broad Fe lines is still nowadays highly debated because the different absorption/emission models are degenerate. Spectral variability studies have the potential to break this degeneracy. I will present the results of a spectral variability RMS survey of the 36 brightest type 1 Seyfert galaxies observed by XMM-Newton for more than 30 ks. More than 80 as already measured, on longer timescales, with RXTE (Markowitz et al. 2004). About half of the sample show lower variability in the soft energy band, indicating that the emission from the soft excess is more stable than the one of the continuum. While the other sources show a soft excess that is as variable as the continuum. About half of the sample do not show an excess of variability where the warm absorber component imprints its stronger features, suggesting that for these sources the soft excess is not produced by a relativistic absorbing wind. In a few bright and well exposed sources it has been possible to measure an excess of variability at the energy of the broad component of the Fe K line, in agreement with the broad emission line interpretation. For the sources where more than one observation was available the stability of the shape of the RMS spectrum has been investigated. Moreover, it will be presented the results of the computation of the excess variance of all the radio quiet type 1 AGN of the XMM-Newton database. The relations between variability, black hole mass, accretion rate and luminosity are investigated and their scatter measured.

Design and synthesis of aminocoumarin derivatives as DPP-IV inhibitors and anticancer agents.

PubMed

Soni, Rina; Soman, Shubhangi S

2018-09-01

DPP-IV "a moonlighting protein" has immerged as promising pathway to control Type 2 diabetes as well as found to play key role in earlier stages of cancer. Here we have reported design, synthesis and applications of aminocoumarin derivatives as DPP-IV inhibitors. Compounds have been synthesized and studied for their DPP-IV inhibition activity. Three compounds have shown moderate inhibition at 100 µM concentration. All compounds were also screened for their anticancer activity against A549 (Lung cancer cell line), MCF-7 (Breast cancer cell line) using MTT assay. One of the compounds has shown very good anticancer activity with IC 50 value 24 ± 0.1 nM against A549 cell line. Copyright © 2018 Elsevier Inc. All rights reserved.

Kill ratio calculation for in-line yield prediction

NASA Astrophysics Data System (ADS)

Lorenzo, Alfonso; Oter, David; Cruceta, Sergio; Valtuena, Juan F.; Gonzalez, Gerardo; Mata, Carlos

1999-04-01

The search for better yields in IC manufacturing calls for a smarter use of the vast amount of data that can be generated by a world class production line.In this scenario, in-line inspection processes produce thousands of wafer maps, number of defects, defect type and pictures every day. A step forward is to correlate these with the other big data- generator area: test. In this paper, we present how these data can be put together and correlated to obtain a very useful yield predicting tool. This correlation will first allow us to calculate the kill ratio, i.e. the probability for a defect of a certain size in a certain layer to kill the die. Then we will use that number to estimate the cosmetic yield that a wafer will have.

Assessment of Durable SiC JFET Technology for +600 C to -125 C Integrated Circuit Operation

NASA Technical Reports Server (NTRS)

Neudeck, P. G.; Krasowski, M. J.; Prokop, N. F.

2011-01-01

Electrical characteristics and circuit design considerations for prototype 6H-SiC JFET integrated circuits (ICs) operating over the broad temperature range of -125 C to +600 C are described. Strategic implementation of circuits with transistors and resistors in the same 6H-SiC n-channel layer enabled ICs with nearly temperature-independent functionality to be achieved. The frequency performance of the circuits declined at temperatures increasingly below or above room temperature, roughly corresponding to the change in 6H-SiC n-channel resistance arising from incomplete carrier ionization at low temperature and decreased electron mobility at high temperature. In addition to very broad temperature functionality, these simple digital and analog demonstration integrated circuits successfully operated with little change in functional characteristics over the course of thousands of hours at 500 C before experiencing interconnect-related failures. With appropriate further development, these initial results establish a new technology foundation for realizing durable 500 C ICs for combustion engine sensing and control, deep-well drilling, and other harsh-environment applications.

Preparation of a generic monoclonal antibody and development of a highly sensitive indirect competitive ELISA for the detection of phenothiazines in animal feed.

PubMed

Wang, Juan; Wang, Yulian; Pan, Yuanhu; Chen, Dongmei; Liu, Zhenli; Feng, Liang; Peng, Dapeng; Yuan, Zonghui

2017-04-15

In this study, a broadly specific monoclonal antibody was prepared and a sensitive monoclonal-based indirect competitive enzyme linked immunosorbent assay (ic-ELISA) was subsequently developed to determine the phenothiazines in animal feed with a simple sample preparation procedure for the first time. The obtained antibody 3A5 was of the immunoglobulin G1 (IgG1) isotype possessing a kappa light chain, which broadly cross-reacted to nine phenothiazines. The limit of detections of the method ranged from 1.1μgkg -1 to 15.3μgkg -1 in the swine feed and the fish feed. The recoveries of the phenothiazines were in the range of 78.2-116.6%. The coefficient of variations were less than 16.7%. A positive correlation (r>0.9249) between the results of the ic-ELISA and the high-performance liquid chromatography were also observed, which indicated that the developed ic-ELISA is reliable and can be used to monitor phenothiazines in animal feed. Copyright © 2016 Elsevier Ltd. All rights reserved.

Synthesis and Anticancer Activity of 3-(Substituted Aroyl)-4-(3,4,5-trimethoxyphenyl)-1H-pyrrole Derivatives.

PubMed

Zhan, Xiao-Ping; Lan, Lan; Wang, Shuai; Zhao, Kai; Xin, Yu-Xuan; Qi, Qi; Wang, Yao-Lin; Mao, Zhen-Min

2017-02-01

A series of 3-(substituted aroyl)-4-(3,4,5-trimethoxyphenyl)-1H-pyrrole derivatives were synthesized and determined for their anticancer activity against eleven cancer cell lines and two normal tissue cell lines using MTT assay. Among the synthesized compounds, compound 3f was the most potent compound against A375, CT-26, HeLa, MGC80-3, NCI-H460 and SGC-7901 cells (IC 50  = 8.2 - 31.7 μm); 3g, 3n and 3a were the most potent compounds against CHO (IC 50  = 8.2 μm), HCT-15 (IC 50  = 21 μm) and MCF-7 cells (IC 50  = 18.7 μm), respectively. Importantly, all the target compounds showed no cytotoxicity towards the normal tissue cell (IC 50  > 100 μm). Thus, these compounds with the potent anticancer activity and low toxicity have potential for the development of new anticancer chemotherapy agents. © 2017 Wiley-VHCA AG, Zurich, Switzerland.

Phase II Trial of Atezolizumab As First-Line or Subsequent Therapy for Patients With Programmed Death-Ligand 1-Selected Advanced Non-Small-Cell Lung Cancer (BIRCH).

PubMed

Peters, Solange; Gettinger, Scott; Johnson, Melissa L; Jänne, Pasi A; Garassino, Marina C; Christoph, Daniel; Toh, Chee Keong; Rizvi, Naiyer A; Chaft, Jamie E; Carcereny Costa, Enric; Patel, Jyoti D; Chow, Laura Q M; Koczywas, Marianna; Ho, Cheryl; Früh, Martin; van den Heuvel, Michel; Rothenstein, Jeffrey; Reck, Martin; Paz-Ares, Luis; Shepherd, Frances A; Kurata, Takayasu; Li, Zhengrong; Qiu, Jiaheng; Kowanetz, Marcin; Mocci, Simonetta; Shankar, Geetha; Sandler, Alan; Felip, Enriqueta

2017-08-20

Purpose BIRCH was designed to examine the efficacy of atezolizumab, a humanized anti-programmed death-ligand 1 (PD-L1) monoclonal antibody, in advanced non-small-cell lung cancer (NSCLC) across lines of therapy. Patients were selected on the basis of PD-L1 expression on tumor cells (TC) or tumor-infiltrating immune cells (IC). Patients and Methods Eligible patients had advanced-stage NSCLC, no CNS metastases, and zero to two or more lines of prior chemotherapy. Patients whose tumors expressed PD-L1 using the SP142 immunohistochemistry assay on ≥ 5% of TC or IC (TC2/3 or IC2/3 [TC or IC ≥ 5% PD-L1-expressing cells, respectively]) were enrolled. Atezolizumab 1,200 mg was administered intravenously every 3 weeks. Efficacy-evaluable patients (N = 659) comprised three cohorts: first line (cohort 1; n = 139); second line (cohort 2; n = 268); and third line or higher (cohort 3; n = 252). The primary end point was independent review facility-assessed objective response rate (ORR; Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1). Secondary end points included median duration of response, progression-free survival, and overall survival (OS). Results BIRCH met its primary objective of demonstrating a significant ORR versus historical controls. With a minimum of 12 months of follow-up, the independent review facility-assessed ORR was 18% to 22% for the three cohorts, and 26% to 31% for the TC3 or IC3 subgroup; most responses are ongoing. Responses occurred regardless of EGFR or KRAS mutation status. The median OS from an updated survival analysis (minimum of 20 month follow up) for cohort 1 was 23.5 months (26.9 months for TC3 or IC3 patients); the median OS in cohorts 2 and 3 was 15.5 and 13.2 months, respectively. The safety profile was similar across cohorts and consistent with previous atezolizumab monotherapy trials. Conclusion BIRCH demonstrated responses with atezolizumab monotherapy in patients with PD-L1-selected advanced NSCLC, with good tolerability. PD-L1 status may serve as a predictive biomarker for identifying patients most likely to benefit from atezolizumab.

Synthesis of Novel Chiral Sulfonamide-Bearing 1,2,4-Triazole-3-thione Analogs Derived from D- and L-Phenylalanine Esters as Potential Anti-Influenza Agents.

PubMed

Başaran, Eyüp; Karaküçük-Iyidoğan, Ayşegül; Schols, Dominique; Oruç-Emre, Emine Elçin

2016-06-01

Novel enantiopure 1,2,4-trizole-3-thiones containing a benzensulfonamide moiety were synthesized via multistep reaction sequence starting with D-phenylalanine methyl ester and L-phenylalanine ethyl ester as a source of chirality. The chemical structures of all compounds were characterized by elemental analysis, UV, IR, (1) H NMR, (13) C NMR, 2D NMR (HETCOR), and mass spectral data. All compounds were tested in vitro antiviral activity against a broad variety of DNA and RNA viruses and in vitro cytostatic activity against murine leukemia (L1210), human T-lymphocyte (CEM) and human cervix carcinoma (HeLa) cell lines. Although enantiopure 1,2,4-triazole-3-thione analogs in (R) configuration emerged as promising anti-influenza A H1N1 subtype in Madin Darby canine kidney cell cultures (MDCK), their enantiomers exhibited no activity. Especially compounds , , , , and (EC50 : 6.5, 6.1, 2.4, 1.6, 1.7 μM, respectively) had excellent activity against influenza A H1N1 subtype compared to the reference drug ribavirin (EC50 : 8.0 μM). Several compounds have been found to inhibit proliferation of L1210, CEM and HeLa cell cultures with IC50 in the 12-53 μM range. Compound and in (R) configuration were the most active compounds (IC50 : 12-22 μM for and IC50 : 19-23 μM for ). Chirality 28:495-513, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Molecular characterization and expression of ADAMTS8 (a disintegrin and metalloproteinase with thrombospondin motifs 8) in chicken.

PubMed

Lee, Ra Ham; Lee, Seokhyun; Kim, Yu Ra; Lee, Hak-Kyo; Song, Ki-Duk

2018-05-31

A disintegrin and metallopeptidase with thrombospondin motifs type 8 (ADAMTS8) is crucial for diverse physiological processes, such as inflammation, tissue morphogenesis, and tumorigenesis. The chicken ADAMTS8 (chADAMTS8) gene was differentially expressed in the kidney following exposure to different calcium concentrations, suggesting a pathological role of this protein in metabolic diseases. We aimed to examine the molecular characteristics of chADAMTS8 and analyze the gene-expression differences in response to Toll-like receptor 3 (TLR3) stimulation. The ADAMTS8 mRNA and amino acid sequences of various species (chicken, duck, cow, mouse, rat, human, chimpanzee, pig, and horse) were retrieved from the Ensembl database and subjected to bioinformatics analyses. Reverse-transcription polymerase chain reaction (RT-PCR) and quantitative PCR (qPCR) experiments were performed with various chicken tissues and the chicken fibroblast DF-1 cell line, which was stimulated with polyinosinic-polycytidylic acid (poly [I:C]; a TLR3 ligand). The ChADAMTS8 gene was predicted to contain three thrombospondin type 1 (TSP1) domains, whose amino acid sequences shared homology among the different species, whereas sequences outside the TSP1 domains (especially the amino-terminal region) were very different. Phylogenetic analysis revealed that chADAMTS8 is evolutionarily clustered in the same clade with that of the duck. chADAMTS8 mRNA was broadly expressed in chicken tissues, and the expression was significantly up-regulated in the DF-1 cells in response to poly (I:C) stimulation (p < 0.05). These results showed that chADAMTS8 may be a target gene for TLR3 signaling. In this report, the genetic information of chicken ADAMTS8 gene, its expression in chicken tissues, and chicken DF-1 cells under the stimulation of TLR3 were shown. The result suggests that chADAMTS8 expression may be induced by viral infection and correlated with TLR3-mediated signaling pathway. Further study of the function of chADAMTS8 during TLR3-dependent inflammation (which represents RNA viral infection) is needed and it will also be important.

Desformylflustrabromine (dFBr) and [3H]dFBr-Labeled Binding Sites in a Nicotinic Acetylcholine Receptor

PubMed Central

Hamouda, Ayman K.; Wang, Ze-Jun; Stewart, Deirdre S.; Jain, Atul D.; Glennon, Richard A.

2015-01-01

Desformylflustrabromine (dFBr) is a positive allosteric modulator (PAM) of α4β2 and α2β2 nAChRs that, at concentrations >1 µM, also inhibits these receptors and α7 nAChRs. However, its interactions with muscle-type nAChRs have not been characterized, and the locations of its binding site(s) in any nAChR are not known. We report here that dFBr inhibits human muscle (αβεδ) and Torpedo (αβγδ) nAChR expressed in Xenopus oocytes with IC50 values of ∼1 μM. dFBr also inhibited the equilibrium binding of ion channel blockers to Torpedo nAChRs with higher affinity in the nAChR desensitized state ([3H]phencyclidine; IC50 = 4 μM) than in the resting state ([3H]tetracaine; IC50 = 60 μM), whereas it bound with only very low affinity to the ACh binding sites ([3H]ACh, IC50 = 1 mM). Upon irradiation at 312 nm, [3H]dFBr photoincorporated into amino acids within the Torpedo nAChR ion channel with the efficiency of photoincorporation enhanced in the presence of agonist and the agonist-enhanced photolabeling inhibitable by phencyclidine. In the presence of agonist, [3H]dFBr also photolabeled amino acids in the nAChR extracellular domain within binding pockets identified previously for the nonselective nAChR PAMs galantamine and physostigmine at the canonical α-γ interface containing the transmitter binding sites and at the noncanonical δ-β subunit interface. These results establish that dFBr inhibits muscle-type nAChR by binding in the ion channel and that [3H]dFBr is a photoaffinity probe with broad amino acid side chain reactivity. PMID:25870334

Cardiomyocyte H9c2 cells present a valuable alternative to fish lethal testing for azoxystrobin.

PubMed

Rodrigues, Elsa T; Pardal, Miguel Â; Laizé, Vincent; Cancela, M Leonor; Oliveira, Paulo J; Serafim, Teresa L

2015-11-01

The present study aims at identifying, among six mammalian and fish cell lines, a sensitive cell line whose in vitro median inhibitory concentration (IC50) better matches the in vivo short-term Sparus aurata median lethal concentration (LC50). IC50s and LC50 were assessed after exposure to the widely used fungicide azoxystrobin (AZX). Statistical results were relevant for most cell lines after 48 h of AZX exposure, being H9c2 the most sensitive cells, as well as the ones which provided the best prediction of fish toxicity, with a LC50,96h/IC50,48h = 0.581. H9c2 cell proliferation upon 72 h of AZX exposure revealed a LC50,96h/IC50,72h = 0.998. Therefore, identical absolute sensitivities were attained for both in vitro and in vivo assays. To conclude, the H9c2 cell-based assay is reliable and represents a suitable ethical alternative to conventional fish assays for AZX, and could be used to get valuable insights into the toxic effects of other pesticides. Copyright © 2015 Elsevier Ltd. All rights reserved.

Q2122-444: A NAKED ACTIVE GALACTIC NUCLEUS FULLY DRESSED

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

Gliozzi, M.; Satyapal, S.; Panessa, F.

Based on previous spectral and temporal optical studies, Q2122-444 has been classified as a naked active galactic nucleus (AGN) or true type 2 AGN, that is, an AGN that genuinely lacks a broad-line region (BLR). Its optical spectrum seemed to possess only narrow forbidden emission lines that are typical of type 2 (obscured) AGNs, but the long-term optical light curve, obtained from a monitoring campaign over more than two decades, showed strong variability, apparently ruling out the presence of heavy obscuration. Here we present the results from a {approx}40 ks XMM-Newton observation of Q2122-444 carried out to shed light onmore » the energetics of this enigmatic AGN. The X-ray analysis was complemented with Australia Telescope Compact Array radio data to assess the possible presence of a jet, and with new NTT/EFOSC2 optical spectroscopic data to verify the actual absence of a BLR. The higher-quality optical data revealed the presence of strong and broad Balmer lines that are at odds with the previous spectral classification of this AGN. The lack of detection of radio emission rules out the presence of a jet. The X-ray data combined with simultaneous UV observations carried out by the Optical Monitor (OM) aboard XMM-Newton confirm that Q2122-444 is a typical type 1 AGN without any significant intrinsic absorption. New estimates of the black hole mass independently obtained from the broad Balmer lines and from a new scaling technique based on X-ray spectral data suggest that Q2122-444 is accreting at a relatively high rate in Eddington units.« less

Accretion dynamics of EX Lupi in quiescence. The star, the spot, and the accretion column

NASA Astrophysics Data System (ADS)

Sicilia-Aguilar, Aurora; Fang, Min; Roccatagliata, Veronica; Collier Cameron, Andrew; Kóspál, Ágnes; Henning, Thomas; Ábrahám, Peter; Sipos, Nikoletta

2015-08-01

Context. EX Lupi is a young, accreting M0 star and the prototype of EXor variable stars. Its spectrum is very rich in emission lines, including many metallic lines with narrow and broad components. The presence of a close companion has also been proposed, based on radial velocity signatures. Aims: We use the metallic emission lines to study the accretion structures and to test the companion hypothesis. Methods: We analyse 54 spectra obtained during five years of quiescence time. We study the line profile variability and the radial velocity of the narrow and broad metallic emission lines. We use the velocity signatures of different species with various excitation conditions and their time dependency to track the dynamics associated with accretion. Results: We observe periodic velocity variations in the broad and the narrow line components, consistent with rotational modulation. The modulation is stronger for lines with higher excitation potentials (e.g. He II), which are likely produced in a confined area very close to the accretion shock. Conclusions: We propose that the narrow line components are produced in the post-shock region, while the broad components originate in the more extended, pre-shock material in the accretion column. All the emission lines suffer velocity modulation due to the rotation of the star. The broad components are responsible for the line-dependent veiling observed in EX Lupi. We demonstrate that a rotationally modulated line-dependent veiling can explain the radial velocity signature of the photospheric absorption lines, making the close-in companion hypothesis unnecessary. The accretion structure is locked to the star and very stable during the five years of observations. Not all stars with similar spectral types and accretion rates show the same metallic emission lines, which could be related to differences in temperature and density in their accretion structure(s). The contamination of photospheric signatures by accretion-related processes can be turned into a very useful tool for determining the innermost details of the accretion channels in the proximity of the star. The presence of emission lines from very stable accretion columns will nevertheless be a very strong limitation for the detection of companions by radial velocity in young stars, given the similarity of the accretion-related signatures with those produced by a companion. Appendices are available in electronic form at http://www.aanda.org

Nonlinear mixed effects dose response modeling in high throughput drug screens: application to melanoma cell line analysis.

PubMed

Ding, Kuan-Fu; Petricoin, Emanuel F; Finlay, Darren; Yin, Hongwei; Hendricks, William P D; Sereduk, Chris; Kiefer, Jeffrey; Sekulic, Aleksandar; LoRusso, Patricia M; Vuori, Kristiina; Trent, Jeffrey M; Schork, Nicholas J

2018-01-12

Cancer cell lines are often used in high throughput drug screens (HTS) to explore the relationship between cell line characteristics and responsiveness to different therapies. Many current analysis methods infer relationships by focusing on one aspect of cell line drug-specific dose-response curves (DRCs), the concentration causing 50% inhibition of a phenotypic endpoint (IC 50 ). Such methods may overlook DRC features and do not simultaneously leverage information about drug response patterns across cell lines, potentially increasing false positive and negative rates in drug response associations. We consider the application of two methods, each rooted in nonlinear mixed effects (NLME) models, that test the relationship relationships between estimated cell line DRCs and factors that might mitigate response. Both methods leverage estimation and testing techniques that consider the simultaneous analysis of different cell lines to draw inferences about any one cell line. One of the methods is designed to provide an omnibus test of the differences between cell line DRCs that is not focused on any one aspect of the DRC (such as the IC 50 value). We simulated different settings and compared the different methods on the simulated data. We also compared the proposed methods against traditional IC 50 -based methods using 40 melanoma cell lines whose transcriptomes, proteomes, and, importantly, BRAF and related mutation profiles were available. Ultimately, we find that the NLME-based methods are more robust, powerful and, for the omnibus test, more flexible, than traditional methods. Their application to the melanoma cell lines reveals insights into factors that may be clinically useful.

Cytotoxic bibenzyl dimers from the stems of Dendrobium fimbriatum Hook.

PubMed

Xu, Feng-Qing; Xu, Fang-Cheng; Hou, Bo; Fan, Wei-Wei; Zi, Cheng-Ting; Li, Yan; Dong, Fa-Wu; Liu, Yu-Qing; Sheng, Jun; Zuo, Zhi-Li; Hu, Jiang-Miao

2014-11-15

The bioassay-guided chemical investigation of the stems of Dendrobium fimbriatum Hook led to the isolation of seven first reported bibenzyl dimers with a linkage of a methylene moiety, fimbriadimerbibenzyls A-G (1-7), together with a new dihydrophenanthrene derivative (S)-2,4,5,9-tetrahydroxy-9,10-dihydrophenanthrene (8) and thirteen known compounds (9-21). The structure of the new compound was established by spectroscopic analysis. Biological evaluation of bibenzyl derivatives against five human cell lines indicated that seven of those compounds exhibited broad-spectrum and cytotoxic activities with IC50 values ranging from 2.2 to 21.2 μM. Those rare bibenzyl dimers exhibited cytotoxic activities in vitro and the cytotoxicity decreased as the number of oxygen-containing groups in the structure decreases. Copyright © 2014 Elsevier Ltd. All rights reserved.

A new method to measure the virial factors in the reverberation mapping of active galactic nuclei

NASA Astrophysics Data System (ADS)

Liu, H. T.; Feng, H. C.; Bai, J. M.

2017-04-01

Based on the gravitational red shift, which is a prediction of Einstein's general relativity theory, of broad optical emission lines in active galactic nuclei (AGNs), a new method is proposed to estimate the virial factors f in measuring black hole masses MRM by the reverberation mapping of AGNs. The factors f can be measured based on two physical quantities, I.e. the gravitational red shifts zg and the full widths at half maxima vFWHM of broad lines. In the past, it has been difficult to determine the factors f for individual AGNs. We apply this new method to several reverberation-mapped type 1 Seyfert galaxies. There is a correlation between f and the radius of the broad-line region (BLR) rBLR, f=5.4 r_{BLR}^{0.3}, for the gravitationally red-shifted broad lines He II, He I, Hβ and Hα in the narrow-line type 1 Seyfert galaxy (NLS1) Mrk 110. This correlation results from the influence of the radiation pressure of the accretion disc on the BLR clouds. This influence seems to be more important than usually thought so in AGNs. Mrk 110 has f ≈ 8-16, distinctly larger than the mean ≈ 1 usually used to estimate MRM for vFWHM. NGC 4593 and NLS1 Mrk 486 have f ≈ 3 and f ≈ 9, respectively. Higher f values of several tens are derived for three other NLS1s. There is a correlation between f and accretion rate dot{M}_{f=1}, f=6.8dot{M}^{0.4}_{f=1} for five objects, where dot{M}_{f=1}=dot{M}_{bullet }/L_{Edd}c^{-2} as f = 1 is assumed when estimating MRM used in the Eddington luminosity LEdd, dot{M}_{bullet } is the mass accretion rate, and c is the speed of light. These larger f values will produce higher MRM values and lower Eddington ratios.

New isopimarane diterpenes and nortriterpene with cytotoxic activity from Ephorbia alatavica Boiss.

PubMed

Rozimamat, Rushangul; Hu, Rui; Aisa, Haji Akber

2018-06-01

Three new isopimarane diterpenes and one new nor-triterpenes, along with five known diterpenes were isolated from the whole areal part of Ephorbia alatavica Boiss. The structures of the new compounds (1-4) were determined based on extensive spectroscopic analysis, including HR-ESIMS, 1D and 2D NMR data. A plausible biosynthetic pathway for new compounds (1-4) were hypothesized. All isolated compounds were screen for cytotoxicity activity against MCF-8, HeLa and A549 cell lines in vitro by MTT assay. New compound 1 and known 9 showed potential cytotoxic activities with IC 50 values of 15.327 μg/mL, 23.066 μg/mL against MCF-8 cell lines, compound1 showed noteworthy cytotoxic activity with IC 50 13.033 μg/mL against A549 cancer cell line. New compounds 2, 4 and 4 showed moderate cytotoxic activities three human cancer lines with IC 50 value around 50 μg/mL, which compared with positive control doxorubicin (DOX). Copyright © 2018 Elsevier B.V. All rights reserved.

Synthesis, Characterization, and Anti-Cancer Activity of Some New N'-(2-Oxoindolin-3-ylidene)-2-propylpentane hydrazide-hydrazones Derivatives.

PubMed

El-Faham, Ayman; Farooq, Muhammad; Khattab, Sherine N; Abutaha, Nael; Wadaan, Mohammad A; Ghabbour, Hazem A; Fun, Hoong-Kun

2015-08-13

Eight novel N'-(2-oxoindolin-3-ylidene)-2-propylpentane hydrazide-hydrazone derivatives 4a-h were synthesized and fully characterized by IR, NMR ((1)H-NMR and (13)C-NMR), elemental analysis, and X-ray crystallography. The cyto-toxicity and in vitro anti-cancer evaluation of the prepared compounds have been assessed against two different human tumour cell lines including human liver (HepG2) and leukaemia (Jurkat), as well as in normal cell lines derived from human embryonic kidney (HEK293) using MTT assay. The compounds 3e, 3f, 4a, 4c, and 4e revealed promising anti-cancer activities in tested human tumour cells lines (IC50 values between 3 and 7 μM) as compared to the known anti-cancer drug 5-Fluorouracil (IC50 32-50 μM). Among the tested compounds, 4a showed specificity against leukaemia (Jurkat) cells, with an IC50 value of 3.14 μM, but this compound was inactive in liver cancer and normal cell lines.

Study of cytotoxic activity, podophyllotoxin, and deoxypodophyllotoxin content in selected Juniperus species cultivated in Poland.

PubMed

Och, Marek; Och, Anna; Cieśla, Łukasz; Kubrak, Tomasz; Pecio, Łukasz; Stochmal, Anna; Kocki, Janusz; Bogucka-Kocka, Anna

2015-06-01

The demand for podophyllotoxin and deoxypodophyllotoxin is still increasing and commercially exploitable sources are few and one of them, Podophyllum hexandrum Royle (Berberidaceae), is a "critically endangered" species. The first aim was to quantify the amount of podophyllotoxin and deoxypodophyllotoxin in 61 Juniperus (Cupressaceae) samples. Cytotoxic activity of podophyllotoxin and ethanolic leaf extracts of Juniperus scopulorum Sarg. "Blue Pacific" and Juniperus communis L. "Depressa Aurea" was examined against different leukemia cell lines. Ultra-performance liquid chromatography (UPLC) analysis was performed with the use of a Waters ACQUITY UPLC(TM) system (Waters Corp., Milford, MA). The peaks of podophyllotoxin and deoxypodophyllotoxin were assigned on the basis of their retention data and mass-to-charge ratio (m/z). Trypan blue assay was performed to obtain IC50 cytotoxicity values against selected leukemia cell lines. Juniperus scopulorum was characterized with the highest level of podophyllotoxin (486.7 mg/100 g DW) while Juniperus davurica Pall. contained the highest amount of deoxypodophyllotoxin (726.8 mg/100 g DW). Podophyllotoxin IC50 cytotoxicity values against J45.01 and CEM/C1 leukemia cell lines were 0.0040 and 0.0286 µg/mL, respectively. Juniperus scopulorum extract examined against J45.01 and HL-60/MX2 leukemia cell lines gave the respective IC50 values: 0.369-9.225 µg/mL. Juniperus communis extract was characterized with the following IC50 cytotoxity values against J45.01 and U-266B1 cell lines: 3.310-24.825 µg/mL. Juniperus sp. can be considered as an alternative source of podophyllotoxin and deoxypodophyllotoxin. Cytotoxic activity of podophyllotoxin and selected leaf extracts of Juniperus sp. against a set of leukemia cell lines was demonstrated.

The seed factor: how a combination of four observables can unveil the location of blazar GeV emission.

NASA Astrophysics Data System (ADS)

Harvey, Adam; Georganopoulos, Markos; Meyer, Eileen

2018-01-01

We present here a method for constraining the emission location of γ-rays in powerful, lined blazars (i.e., flat spectrum radio quasars (FSRQs)). We develop a diagnostic criteria, which we term the seed factor, to differentiate between γ-ray emission due to external Compton (EC) scattering in the broad line region (BLR) and the molecular torus (MT). The seed factor is determined entirely by four observable quantities; the synchrotron and inverse Compton (IC) peak frequencies, and the respective peak luminosities. It may thus be possible to use the seed factor to constrain the emission location in a model-independent way.We also present preliminary results of our analysis regarding the seed factor in quasi-simultaneous multi-wavelength SEDs from the Fermi LAT Bright AGN Sample (LBAS), historical data from the ASDC SED Builder of FSRQs in the the Monitoring Of Jets in Active galactic nuclei with VLBA Experiments (MOJAVE) sample, and quasi-simultaneous multi-wavelength SEDs from the Dynamic SEDs of southern blazars (DSSB) sample.

Synthesis, Characterization, Anticancer and Antibacterial Activity of Some Novel Pyrano[2,3-d]pyrimidinone Carbonitrile Derivatives.

PubMed

Aremu, Oluwole S; Gopaul, Kaalin; Kadam, Pramod; Singh, Moganavelli; Mocktar, Chunderika; Singh, Parvesh; Koorbanally, Neil A

2017-01-01

Pyrimidines have widespread activity and have shown potent antibacterial and anticancer activity. To synthesise a range of pyrimidine diones and test them for their antibacterial and anticancer activity. The pyranopyrimidin-2,4-dione derivatives (1-7) were synthesized in a one-pot reaction by reacting malononitrile and barbituric acid with several aromatic aldehydes in the presence of 1,4-diazabicyclo[2.2.2]octane (DABCO) in aqueous medium. The compounds were tested for their antibacterial activity using the broth microdilution method and for their cytotoxicity against three cell lines, HeLa (cervical cancer), Caco-2 (human colon adenocarcinoma) and HEK 293 (human embryonic kidney cells) using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide) assay. Compounds 1-7 were successfully synthesized in yields of >90%. The 3,4-dihydroxyaryl (3) and the 2,5- dimethoxyaryl (7) derivatives were novel. Compounds 3, 5 (4'-methoxy derivative) and 6 (2',3'-dimethoxy derivative) showed antibacterial activity comparable to or better than the standard ampicillin. All the test compounds 1-7 showed good anticancer activity. The IC50 values ranged from 3.46 to 37.13 μM (HeLa); 136.78 to 297.05 μM (Caco-2) and 137.84 to 333.81 μM (HEK293). The best activity was seen in the HeLa cell line when compared to the standard 5FU (5-Fluorouracil IC50 of 41.85 μM), with 1, 2, 5 and 7 having IC50 values of 10.64, 3.46, 4.36 and 4.44 μM respectively. Additionally, two representative compounds (1 and 7) found to be potent against the two cell lines (HeLa and HEK 293) were docked into the binding site of human kinesin Eg5 with the aim of predicting their binding propensities and to establish their mechanism of action. The Lipinski parameters of these compounds were also computed and analysed for their drug-likeness. Compound 6 is an excellent candidate for a broad spectrum antibiotic with MBCs of 45.6-365.2 μM, while both 3 and 6 have the potential to be developed into an antibiotic against MRSA, with MBCs of 183-199 μM. Since all synthesized compounds showed IC50 values of 10 μM or less especially against the HeLa cells, they can be considered good lead compounds for anticancer agents. Additionally, the docking simulations suggested a good binding affinity of the compounds with Eg5 and indicated their anti-cancer action, at least partially, through its inhibition. The predicted Lipinski descriptors also indicated the potential of these compounds as an orally active drug. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Human Monoclonal Antibody-Based Therapy in the Treatment of Invasive Candidiasis

PubMed Central

Bugli, Francesca; Cacaci, Margherita; Martini, Cecilia; Torelli, Riccardo; Posteraro, Brunella; Sanguinetti, Maurizio; Paroni Sterbini, Francesco

2013-01-01

Invasive candidiasis (IC) represents the leading fungal infection of humans causing life-threatening disease in immunosuppressed and neutropenic individuals including also the intensive care unit patients. Despite progress in recent years in drugs development for the treatment of IC, morbidity and mortality rates still remain very high. Historically, cell-mediated immunity and innate immunity are considered to be the most important lines of defense against candidiasis. Nevertheless recent evidence demonstrates that antibodies with defined specificities could act with different degrees showing protection against systemic and mucosal candidiasis. Mycograb is a human recombinant monoclonal antibody against heat shock protein 90 (Hsp90) that was revealed to have synergy when combined with fluconazole, caspofungin, and amphotericin B against a broad spectrum of Candida species. Furthermore, recent studies have established an important role for Hsp90 in mediating Candida resistance to echinocandins, giving to this antibody molecule even more attractive biological properties. In response to the failure of marketing authorization by the CHMP (Committee for Medicinal Products for Human Use) a new formulation of Mycograb, named Mycograb C28Y variant, with an amino acid substitution was developed in recent years. First data on Mycograb C28Y variant indicate that this monoclonal antibody lacked efficacy in a murine candidiasis model. PMID:23878583

Biological evaluation of some new N-(2,6-dimethoxypyrimidinyl) thioureido benzenesulfonamide derivatives as potential antimicrobial and anticancer agents.

PubMed

Ghorab, Mostafa M; Alsaid, Mansour S; El-Gaby, Mohamed S A; Safwat, Nesreen A; Elaasser, Mahmoud M; Soliman, Aiten M

2016-11-29

A series of novel heterocyclic thioureas 3a-u containing sulfonamide moiety have been synthesized by the condensation of isothiocyanatobenzenesulfonamide 2 with a variety of heterocyclic amines. The newly synthesized heterocyclic thioureas were investigated for their antimicrobial and anticancer activity. The in vitro antibacterial and antifungal activity were done using well diffusion method. Interestingly, compounds 3j and 3m, showed similar or better activity compared with the reference drug against the tested microorganisms. Although, 3j was less active among its analogues to inhibit the breast carcinoma cells, it exhibit strong broad spectrum antimicrobial activities. However, The results of the cytotoxic activity revealed that compound 3p was the most active against the breast carcinoma cell line (MCF-7) giving promising IC 50 value of 1.72 μg/mL, compared with reference drug (5-flourouracil) with IC 50 value of 4.8 μg/mL. The most potent compounds in cytotoxic activity 3b and 3p were further docked inside the active site of CAIX and were found to exhibit a proper binding with the active site amino acids according to their bond lengths, angles and conformational energy. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Ultrasonography of the lungs and pleura in healthy camels (Camelus dromedarius).

PubMed

Tharwat, Mohamed

2013-09-01

This study describes ultrasonography of the lungs and pleura in healthy camels (Camelus dromedarius). The different layers of the thoracic wall appeared as narrow bands of variable echogenicity. Reverberation artefacts appeared as lines of variable echogenicity that ran parallel to the pulmonary surface medial to the pleura. Because of its air content, the pulmonary parenchyma was not visualised in all camels. On the right side, the pulmonary surface was seen in the 5th through the 10th intercostal space (ICS). In addition, it was imaged in the 11th ICS in 20 camels and in the 4th ICS in three camels. The dimension of the ventral lung border was largest at the 4th ICS and smallest at the 11th ICS. The echogenic line on the surface of the lung, consisting of the costal and the parietal pleurae, was 1 to 4 mm thick. The left pulmonary surface and pleura were imaged with approximately the same frequencies as the right side. At this side, only the pulmonary surface and pleura were imaged in 15 camels in the 11th ICS. In conclusion, ultrasonography of the lungs and pleura provides information that can be used as a reference when examining camels suspected to have respiratory diseases.

The Cambridge-Cambridge x-ray serendipity survey. 2: Classification of x-ray luminous galaxies

NASA Technical Reports Server (NTRS)

Boyle, B. J.; Mcmahon, R. G.; Wilkes, B. J.; Elvis, Martin

1994-01-01

We present the results of an intermediate-resolution (1.5 A) spectroscopic study of 17 x-ray luminous narrow emission-line galaxies previously identified in the Cambridge-Cambridge ROSAT Serendipity Survey and the Einstein Extended Medium Sensitivity Survey. Emission-line ratios reveal that the sample is composed of ten Seyfert and seven starburst galaxies. Measured linewidths for the narrow H alpha emission lines lie in the range 170 - 460 km s(exp -1). Five of the objects show clear evidence for asymmetry in the (OIII) lambda 5007 emission-line profile. Broad H alpha emission is detected in six of the Seyfert galaxies, which range in type from Seyfert 1.5 to 2. Broad H beta emission is only detected in one Seyfert galaxy. The mean full width at half maximum for the broad lines in the Seyfert galaxies is FWHM = 3900 +/- 1750 km s(exp -1). Broad (FWHM = 2200 +/- 600 km s(exp -1) H alpha emission is also detected in three of the starburst galaxies, which could originate from stellar winds or supernovae remnants. The mean Balmer decrement for the sample is H alpha / H beta = 3, consistent with little or no reddening for the bulk of the sample. There is no evidence for any trend with x-ray luminosity in the ratio of starburst galaxies to Seyfert galaxies. Based on our previous observations, it is therefore likely that both classes of object comprise approximately 10 percent of the 2 keV x-ray background.

The BAT AGN Spectroscopic Survey (BASS)

NASA Astrophysics Data System (ADS)

Koss, Michael

2017-08-01

We present the Swift BAT AGN Spectroscopic Survey (BASS) and discus the first four papers. The catalog represents an unprecedented census of hard-X-ray selected AGN in the local universe, with ~90% of sources at z<0.2. Starting from an all-sky catalog of AGN detected based on their 14-195 keV flux from the 70-month Swift/BAT catalog, we analyze a total of 1279 optical spectra, taken from twelve different telescopes, for a total of 642 spectra of unique AGN. We present the absorption and emission line measurements as well as black hole masses and accretion rates for the majority of obscured and un-obscured AGN (473), representing more than a factor of 10 increase from past studies. Consistent with previous surveys, we find an increase in the fraction of un-obscured (type 1) AGN, as measured from broad Hbeta and Halpha, with increasing 14-195 keV and 2-10 keV luminosity. We find the FWHM of the emission lines to show broad agreement with the X-ray obscuration measurements. Compared to narrow line AGN in the SDSS, the X-ray selected AGN in our sample with emission lines have a larger fraction of dustier galaxies suggesting these types of galaxies are missed in optical AGN surveys using emission line diagnostics.

Preclinical optimization of a broad-spectrum anti-bladder cancer tri-drug regimen via the Feedback System Control (FSC) platform

NASA Astrophysics Data System (ADS)

Liu, Qi; Zhang, Cheng; Ding, Xianting; Deng, Hui; Zhang, Daming; Cui, Wei; Xu, Hongwei; Wang, Yingwei; Xu, Wanhai; Lv, Lei; Zhang, Hongyu; He, Yinghua; Wu, Qiong; Szyf, Moshe; Ho, Chih-Ming; Zhu, Jingde

2015-06-01

Therapeutic outcomes of combination chemotherapy have not significantly advanced during the past decades. This has been attributed to the formidable challenges of optimizing drug combinations. Testing a matrix of all possible combinations of doses and agents in a single cell line is unfeasible due to the virtually infinite number of possibilities. We utilized the Feedback System Control (FSC) platform, a phenotype oriented approach to test 100 options among 15,625 possible combinations in four rounds of assaying to identify an optimal tri-drug combination in eight distinct chemoresistant bladder cancer cell lines. This combination killed between 82.86% and 99.52% of BCa cells, but only 47.47% of the immortalized benign bladder epithelial cells. Preclinical in vivo verification revealed its markedly enhanced anti-tumor efficacy as compared to its bi- or mono-drug components in cell line-derived tumor xenografts. The collective response of these pathways to component drugs was both cell type- and drug type specific. However, the entire spectrum of pathways triggered by the tri-drug regimen was similar in all four cancer cell lines, explaining its broad spectrum killing of BCa lines, which did not occur with its component drugs. Our findings here suggest that the FSC platform holdspromise for optimization of anti-cancer combination chemotherapy.

In vitro antiproliferative/cytotoxic activity on cancer cell lines of a cardanol and a cardol enriched from Thai Apis mellifera propolis.

PubMed

Teerasripreecha, Dungporn; Phuwapraisirisan, Preecha; Puthong, Songchan; Kimura, Kiyoshi; Okuyama, Masayuki; Mori, Haruhide; Kimura, Atsuo; Chanchao, Chanpen

2012-03-30

Propolis is a complex resinous honeybee product. It is reported to display diverse bioactivities, such as antimicrobial, anti-inflammatory and anti-tumor properties, which are mainly due to phenolic compounds, and especially flavonoids. The diversity of bioactive compounds depends on the geography and climate, since these factors affect the floral diversity. Here, Apis mellifera propolis from Nan province, Thailand, was evaluated for potential anti-cancer activity. Propolis was sequentially extracted with methanol, dichloromethane and hexane and the cytotoxic activity of each crude extract was assayed for antiproliferative/cytotoxic activity in vitro against five human cell lines derived from duet carcinoma (BT474), undifferentiated lung (Chaco), liver hepatoblastoma (Hep-G(2)), gastric carcinoma (KATO-III) and colon adenocarcinoma (SW620) cancers. The human foreskin fibroblast cell line (Hs27) was used as a non-transformed control. Those crude extracts that displayed antiproliferative/cytotoxic activity were then further fractionated by column chromatography using TLC-pattern and MTT-cytotoxicity bioassay guided selection of the fractions. The chemical structure of each enriched bioactive compound was analyzed by nuclear magnetic resonance and mass spectroscopy. The crude hexane and dichloromethane extracts of propolis displayed antiproliferative/cytotoxic activities with IC(50) values across the five cancer cell lines ranging from 41.3 to 52.4 μg/ml and from 43.8 to 53.5 μg/ml, respectively. Two main bioactive components were isolated, one cardanol and one cardol, with broadly similar in vitro antiproliferation/cytotoxicity IC(50) values across the five cancer cell lines and the control Hs27 cell line, ranging from 10.8 to 29.3 μg/ml for the cardanol and < 3.13 to 5.97 μg/ml (6.82 - 13.0 μM) for the cardol. Moreover, both compounds induced cytotoxicity and cell death without DNA fragmentation in the cancer cells, but only an antiproliferation response in the control Hs27 cells However, these two compounds did not account for the net antiproliferation/cytotoxic activity of the crude extracts suggesting the existence of other potent compounds or synergistic interactions in the propolis extracts. This is the first report that Thai A. mellifera propolis contains at least two potentially new compounds (a cardanol and a cardol) with potential anti-cancer bioactivity. Both could be alternative antiproliferative agents for future development as anti-cancer drugs.

Synthesis and cytotoxic activity of two steroids: icogenin aglycone analogs.

PubMed

Guan, Yu-Yao; Li, Shu-Zhen; Lei, Ping-Sheng

2017-05-01

During the process of icogenin analog research, we obtained two cytotoxic steroids: compound 4 and compound 6 casually. Their in vitro antitumor activities were tested by the standard MTT assay. The results disclosed that compound 4 (IC 50  = 3.65-6.90 μM) showed potential antitumor activities against HELA, KB cell lines and compound 6 (IC 50  = 2.40-9.05 μM) showed potential antitumor activities against HELA, BGC-823, KB, A549, HCT-8 cell lines.

Broad-spectrum non-nucleoside inhibitors for caliciviruses.

PubMed

Netzler, Natalie E; Enosi Tuipulotu, Daniel; Eltahla, Auda A; Lun, Jennifer H; Ferla, Salvatore; Brancale, Andrea; Urakova, Nadya; Frese, Michael; Strive, Tanja; Mackenzie, Jason M; White, Peter A

2017-10-01

Viruses of the Caliciviridae cause significant and sometimes lethal diseases, however despite substantial research efforts, specific antivirals are lacking. Broad-spectrum antivirals could combat multiple viral pathogens, offering a rapid solution when no therapies exist. The RNA-dependent RNA polymerase (RdRp) is an attractive antiviral target as it is essential for viral replication and lacks mammalian homologs. To focus the search for pan-Caliciviridae antivirals, the RdRp was probed with non-nucleoside inhibitors (NNIs) developed against hepatitis C virus (HCV) to reveal both allosteric ligands for structure-activity relationship enhancement, and highly-conserved RdRp pockets for antiviral targeting. The ability of HCV NNIs to inhibit calicivirus RdRp activities was assessed using in vitro enzyme and murine norovirus cell culture assays. Results revealed that three NNIs which bound the HCV RdRp Thumb I (TI) site also inhibited transcriptional activities of six RdRps spanning the Norovirus, Sapovirus and Lagovirus genera of the Caliciviridae. These NNIs included JTK-109 (RdRp inhibition range: IC 50 4.3-16.6 μM), TMC-647055 (IC 50 range: 18.8-45.4 μM) and Beclabuvir (IC 50 range: 23.8->100 μM). In silico studies and site-directed mutagenesis indicated the JTK-109 binding site was within the calicivirus RdRp thumb domain, in a pocket termed Site-B, which is highly-conserved within all calicivirus RdRps. Additionally, RdRp inhibition assays revealed that JTK-109 was antagonistic with the previously reported RdRp inhibitor pyridoxal-5'-phosphate-6-(2'-naphthylazo-6'-nitro-4',8'-disulfonate) tetrasodium salt (PPNDS), that also binds to Site-B. Moreover, like JTK-109, PPNDS was also a potent inhibitor of polymerases from six viruses spanning the three Caliciviridae genera tested (IC 50 range: 0.1-2.3 μM). Together, this study demonstrates the potential for de novo development of broad-spectrum antivirals that target the highly-conserved RdRp thumb pocket, Site-B. We also revealed three broad-spectrum HCV NNIs that could be used as antiviral scaffolds for further development against caliciviruses and other viruses. Copyright © 2017 Elsevier B.V. All rights reserved.

Oleanane-type saponins from Anemone taipaiensis and their cytotoxic activities.

PubMed

Wang, Xiaoyang; Zhang, Wei; Gao, Kai; Lu, Yunyang; Tang, Haifeng; Sun, Xiaoli

2013-09-01

Phytochemical investigation of the n-BuOH extract of the rhizomes of Anemone taipaiensis led to the isolation of three new oleanane-type triterpenoid saponins (1-3), together with four known saponins (4-7). Their structures were elucidated on the basis of spectroscopic analysis and chemical derivatization. All the compounds were isolated for the first time from A. taipaiensis. The cytotoxicity of these compounds was evaluated in five human cancer cell lines including A549 (lung carcinoma), HeLa (cervical carcinoma), HepG2 (hepatocellular carcinoma), HL-60 (promyelocytic leukemia), and U87MG (glioblastoma). The monodesmosidic saponin 4 exhibited cytotoxic activity toward all cancer cell lines, with IC50 values ranging from 6.42 to 18.16 μM. In addition, the bisdesmosidic saponins 1 and 7 showed selective cytotoxicity against the U87MG cells. Copyright © 2013 Elsevier B.V. All rights reserved.

Cytotoxic oleanane-type triterpenoid saponins from the Rhizomes of Anemone rivularis var. flore-minore.

PubMed

Wang, Xiaoyang; Wang, Minchang; Xu, Min; Wang, Yi; Tang, Haifeng; Sun, Xiaoli

2014-02-18

Phytochemical investigation of the n-BuOH extract of the rhizomes of Anemone rivularis var. flore-minore led to the isolation of five new oleanane-type triterpenoid saponins 1-5, together with five known saponins 6-10. Their structures were determined by the extensive use of 1D and 2D NMR experiments, along with ESIMS analyses and acid hydrolysis. The aglycone of 4 and 5 was determined as 21α-hydroxyoleanolic acid, which was reported in this genus for the first time. The cytotoxicity of these compounds was evaluated against four human cancer cell line, including HL-60 (promyelocytic leukemia), HepG2 (hepatocellular carcinoma), A549 (lung carcinoma) and HeLa (cervical carcinoma). The monodesmosidic saponins 6-8 exhibited cytotoxic activity toward all tested cancer cell lines, with IC50 values in the 7.25-22.38 μM range.

Using NCAP to predict RFI effects in linear bipolar integrated circuits

NASA Astrophysics Data System (ADS)

Fang, T.-F.; Whalen, J. J.; Chen, G. K. C.

1980-11-01

Applications of the Nonlinear Circuit Analysis Program (NCAP) to calculate RFI effects in electronic circuits containing discrete semiconductor devices have been reported upon previously. The objective of this paper is to demonstrate that the computer program NCAP also can be used to calcuate RFI effects in linear bipolar integrated circuits (IC's). The IC's reported upon are the microA741 operational amplifier (op amp) which is one of the most widely used IC's, and a differential pair which is a basic building block in many linear IC's. The microA741 op amp was used as the active component in a unity-gain buffer amplifier. The differential pair was used in a broad-band cascode amplifier circuit. The computer program NCAP was used to predict how amplitude-modulated RF signals are demodulated in the IC's to cause undesired low-frequency responses. The predicted and measured results for radio frequencies in the 0.050-60-MHz range are in good agreement.

High concentrations of AGE-LDL and oxidized LDL in circulating immune complexes are associated with progression of retinopathy in type 1 diabetes.

PubMed

Lopes-Virella, Maria F; Baker, Nathaniel L; Hunt, Kelly J; Lyons, Timothy J; Jenkins, Alicia J; Virella, Gabriel

2012-06-01

To determine whether immunocomplexes (ICs) containing advanced glycation end product (AGE)-LDL (AGE-LDL) and oxidized LDL (oxLDL) contribute to the development of retinopathy over a 16-year period in subjects with type 1 diabetes. Levels of AGE-LDL and oxLDL in ICs were measured in 517 patients of the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) cohort. Retinopathy was assessed by stereoscopic fundus photography. Cox proportional hazards models were used to assess the effect of AGE-LDL-ICs and oxLDL-ICs on retinopathy progression. In unadjusted models, higher baseline levels of AGE-LDL-ICs and oxLDL-ICs significantly predicted progression of diabetic retinopathy outcomes. After adjustment by study-design variables (treatment group, retinopathy cohort, duration of type 1 diabetes, and baseline albumin excretion rate [AER], hemoglobin A(1c) (HbA(1c)), and Early Treatment Diabetic Retinopathy Study [ETDRS] score), one SD increase in IC levels was associated with 47% (hazard ratio [HR] 1.47 [95% CI 1.19-1.81]; AGE-LDL-IC) and 45% (1.45 [1.17-1.80]; oxLDL-IC) increased risk of developing proliferative diabetic retinopathy (PDR) and 37% (1.37 [1.12-1.66]; to both ICs) increased risk of progressing to severe nonproliferative retinopathy. Analyses were stratified by retinopathy cohort because results differed between primary and secondary cohorts. For AGE-LDL-ICs, HR for progression to PDR was 2.38 (95% CI 1.30-4.34) in the primary cohort and attenuated in the secondary cohort (1.29 [1.03-1.62]). Similar results were observed for oxLDL-ICs. Increased levels of AGE-LDL and oxLDL in ICs are associated with increased risk for progression to advanced retinopathy in patients with type 1 diabetes, indicating that the antibody response to modified LDL plays a significant role in retinopathy progression.

Anti-Proliferative Effect and Phytochemical Analysis of Cymbopogon citratus Extract

PubMed Central

Halabi, Mohammed F.; Sheikh, Bassem Y.

2014-01-01

The antiproliferative and antioxidant potential of Cymbopogon citratus (Lemon grass) extracts were investigated. The extracts were isolated by solvent maceration method and thereafter subjected to antiproliferative activity test on five different cancer cells: human colon carcinoma (HCT-116), breast carcinoma (MCF-7 and MDA-MB 231), ovarian carcinoma (SKOV-3 and COAV), and a normal liver cell line (WRL 68). The cell viability was determined using MTT assay. The DPPH radical scavenging assay revealed a concentration dependent trend. A maximum percentage inhibition of 45% and an IC50 of 278 μg/mL were observed when aqueous extract was evaluated. In contrast, 48.3% and IC50 of 258.9 μg/mL were observed when 50% ethanolic extract was evaluated. Both extracts at concentration of 50 to 800 μg/mL showed appreciative metal chelating activity with IC50 value of 172.2 ± 31 μg/mL to 456.5 ± 30 μg/mL. Depending on extraction solvent content, extract obtained from 50% ethanolic solvent proved to be more potent on breast cancer MCF-7 cell line (IC50 = 68 μg/mL). On the other hand, 90% ethanolic extract showed a moderate potency on the ovarian cancer (COAV) and MCF-7 cells having an IC50 of 104.6 μg/mL each. These results suggested antiproliferative efficacy of C. citratus ethanolic extract against human cancer cell lines. PMID:24791006

Chest Wall Thickness and Decompression Failure: A Systematic Review and Meta-analysis Comparing Anatomic Locations in Needle Thoracostomy

PubMed Central

Laan, Danuel V.; Vu, Trang Diem N.; Thiels, Cornelius A.; Pandian, T. K.; Schiller, Henry J.; Murad, M. Hassan; Aho, Johnathon M.

2015-01-01

Introduction Current Advanced Trauma Life Support guidelines recommend decompression for thoracic tension physiology using a 5-cm angiocatheter at the second intercostal space (ICS) on the midclavicular line (MCL). High failure rates occur. Through systematic review and meta-analysis, we aimed to determine the chest wall thickness (CWT) of the 2nd ICS-MCL, the 4th/5th ICS at the anterior axillary line (AAL), the 4th/5th ICS mid axillary line (MAL) and needle thoracostomy failure rates using the currently recommended 5-cm angiocatheter. Methods A comprehensive search of several databases from their inception to July 24, 2014 was conducted. The search was limited to the English language, and all study populations were included. Studies were appraised by two independent reviewers according to a priori defined PRISMA inclusion and exclusion criteria. Continuous outcomes (CWT) were evaluated using weighted mean difference and binary outcomes (failure with 5-cm needle) were assessed using incidence rate. Outcomes were pooled using the random-effects model. Results The search resulted in 34,652 studies of which 15 were included for CWT analysis, 13 for NT effectiveness. Mean CWT was 42.79 mm (95% CI, 38.78–46.81) at 2nd ICS-MCL, 39.85 mm (95% CI, 28.70–51.00) at MAL, and 34.33 mm (95% CI, 28.20–40.47) at AAL (P=0.08). Mean failure rate was 38% (95% CI, 24–54) at 2nd ICS-MCL, 31% (95% CI, 10–64) at MAL, and 13% (95% CI, 8–22) at AAL (P=0.01). Conclusion Evidence from observational studies suggests that the 4th/5th ICS-AAL has the lowest predicted failure rate of needle decompression in multiple populations. PMID:26724173

Chest wall thickness and decompression failure: A systematic review and meta-analysis comparing anatomic locations in needle thoracostomy.

PubMed

Laan, Danuel V; Vu, Trang Diem N; Thiels, Cornelius A; Pandian, T K; Schiller, Henry J; Murad, M Hassan; Aho, Johnathon M

2016-04-01

Current Advanced Trauma Life Support guidelines recommend decompression for thoracic tension physiology using a 5-cm angiocatheter at the second intercostal space (ICS) on the midclavicular line (MCL). High failure rates occur. Through systematic review and meta-analysis, we aimed to determine the chest wall thickness (CWT) of the 2nd ICS-MCL, the 4th/5th ICS at the anterior axillary line (AAL), the 4th/5th ICS mid axillary line (MAL) and needle thoracostomy failure rates using the currently recommended 5-cm angiocatheter. A comprehensive search of several databases from their inception to July 24, 2014 was conducted. The search was limited to the English language, and all study populations were included. Studies were appraised by two independent reviewers according to a priori defined PRISMA inclusion and exclusion criteria. Continuous outcomes (CWT) were evaluated using weighted mean difference and binary outcomes (failure with 5-cm needle) were assessed using incidence rate. Outcomes were pooled using the random-effects model. The search resulted in 34,652 studies of which 15 were included for CWT analysis, 13 for NT effectiveness. Mean CWT was 42.79 mm (95% CI, 38.78-46.81) at 2nd ICS-MCL, 39.85 mm (95% CI, 28.70-51.00) at MAL, and 34.33 mm (95% CI, 28.20-40.47) at AAL (P=.08). Mean failure rate was 38% (95% CI, 24-54) at 2nd ICS-MCL, 31% (95% CI, 10-64) at MAL, and 13% (95% CI, 8-22) at AAL (P=.01). Evidence from observational studies suggests that the 4th/5th ICS-AAL has the lowest predicted failure rate of needle decompression in multiple populations. Level 3 SR/MA with up to two negative criteria. Therapeutic. Copyright © 2015 Elsevier Ltd. All rights reserved.

Synthesis of novel fluorinated chalcones derived from 4‧-morpholinoacetophenone and their antiproliferative effects

NASA Astrophysics Data System (ADS)

Kurşun Aktar, Bedriye Seda; Oruç-Emre, Emine Elçin; Demirtaş, Ibrahim; Yaglioglu, Ayse Sahin; Guler, Caglar; Adem, Sevki; Karaküçük Iyidoğan, Ayşegül

2017-12-01

The fluorinated chalcones were synthesized by Claisen-Schmidt condensation between 4‧-morpholineacetophenone and various fluorinated benzaldehydes in the presence of NaOH in methanol. The synthesized compounds [1-7] were evaluated their antiproliferative activity against HeLa and C6 cell lines. Among them, compounds 4 and 5 were determined to have anticancer activity against HeLa cells line (IC50 values of 7.74 and 6.10 μg/mL, respectively). The anticancer activity results were shown that compounds 3, and 6 had inhibitory against C6 cells (IC50 values of 12.80 and 4.16 μg/mL, respectively). The compounds 1 and 2 had high antiproliferative activity with non-cytotoxicity. All of the new compounds, except for compound 4 showed inhibition against the human isozyme hCA I with IC50 in the range of 0.5-1,16 mM. Pyruvate kinase M2 (PKM2) was effectively inhibited by compound 4 with IC50 = 26 μM.

Optimization of Antitumor Modulators of Pre-mRNA Splicing

PubMed Central

Lagisetti, Chandraiah; Palacios, Gustavo; Goronga, Tinopiwa; Freeman, Burgess; Caufield, William; Webb, Thomas R.

2014-01-01

The spliceosome regulates pre-mRNA splicing, which is a critical process in normal mammalian cells. Recently recurrent mutations in numerous spliceosomal proteins have been associated with a number of cancers. Previously natural product antitumor agents have been shown to interact with one of the proteins that is subject to recurrent mutations (SF3B1). We report the optimization of a class of tumor-selective spliceosome modulators, which demonstrate significant in vivo antitumor activity. This optimization culminated in the discovery of sudemycin D6, which shows potent cytotoxic activity in the melanoma line SK-MEL-2 (IC50= 39 nM) and other tumor lines, including: JeKo-1 (IC50= 26 nM), HeLa (IC50= 50 nM), and SK-N-AS (IC50= 81 nM). We also report improved processes for the synthesis of these compounds. Our work supports the idea that sudemycin D6 is worthy of further investigation as a novel preclinical anticancer agent with application in the treatment of numerous human cancers. PMID:24325474

Pre-main-sequence stars in the young cluster IC 2391

NASA Technical Reports Server (NTRS)

Stauffer, John; Hartmann, Lee W.; Jones, Burton F.; Mcnamara, Brian R.

1989-01-01

Seven or eight new, late-type members of the poor open cluster IC 2391 are identified, and membership is confirmed for two other stars. The new members fall approximately along a 3 x 10 to the 7th yr isochrone, which is the age estimated for the cluster on the basis of it super main-seqence turnoff. Echelle spectra were obtained for the most probable cluster members. Most show H-alpha in emission and a strong Li 6707 A absorption line, and a few are rapid rotators. The Li abundances for cluster stars cooler than the sun are considerably less than the primordial Li abundance, providing the first direct evidence for substantial premain-sequence Li burning. The rotational velocities show a range from about 15 to 150 km/s, with a distribution of rotational velocities not significantly different from that observed for low-mass stars in the Pleiades.

Synthesis and Biological Evaluation of 1-(2-Aminophenyl)-3-arylurea Derivatives as Potential EphA2 and HDAC Dual Inhibitors.

PubMed

Zhu, Yong; Ran, Ting; Chen, Xin; Niu, Jiaqi; Zhao, Shuang; Lu, Tao; Tang, Weifang

2016-01-01

A series of 1-(2-aminophenyl)-3-arylurea novel derivatives were synthesized and evaluated against Ephrin type-A receptor 2 (EphA2) and histone deacetylases (HDACs) kinase. Most of the compounds exhibited inhibitory activity against EphA2 and HDAC. The antiproliferative activities were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) (thiazolyl blue, tetrazolium blue) against the human cancer cell lines HCT116, K562 and MCF7. Compounds 5a and b showed the most potent inhibitory activity against EphA2 and HDAC. However, compound 5b exhibited higher potency against HCT116 (IC50=5.29 µM) and MCF7 (IC50=7.42 µM). 1-(2-Aminophenyl)-3-arylurea analogues may serve as new EphA2-HDAC dual inhibitors.

Luminous clusters of Wolf-Rayet stars in the SBmIII galaxy NGC 4214

NASA Technical Reports Server (NTRS)

Sargent, Wallace L. W.; Filippenko, Alexei V.

1991-01-01

Observations are reported of strong broad emission lines attributed to WR stars in the spectra of several bright knots in the nearby Magellanic irregular galaxy NGC 4214 (classified as type SBmIII), in addition to the emission produced by the more prevalent WN stars). Data are presented on measurements of the line fluxes, the line equivalent widths, and continuum flux densities in the four observed knots, showing that the strongest WR lines generally appear in knots having the most luminous stellar continuum. The significance of this observation is discussed.

Heterogeneity in cancer cells: variation in drug response in different primary and secondary colorectal cancer cell lines in vitro.

PubMed

Arul, Melanie; Roslani, April Camilla; Cheah, Swee Hung

2017-05-01

Tumor heterogeneity may give rise to differential responses to chemotherapy drugs. Therefore, unraveling tumor heterogeneity has an implication for biomarker discovery and cancer therapeutics. To test this phenomenon, we investigated the differential responses of three secondary colorectal cancer cell lines of different origins (HCT116, HT29, and SW620 cells) and four novel primary cell lines obtained from different colorectal cancer patients to 5-fluorouracil (5-FU) and oxaliplatin (L-OHP) and explored the differences in gene expression among the primary cell lines in response to exposure to cytotoxic drugs. Cells were exposed to different doses of 5-FU and L-OHP separately or in combinations of equitoxic drug or equimolar drug ratios (median effect of Chou-Talalay principle). Cell viability was assessed using MTT assay and the respective IC 50 values were determined. Changes in gene expression in primary cell lines after exposure to the same drug doses were compared using real-time PCR array. The sensitivities (IC 50 ) of different cell lines, both secondary and primary, to 5-FU and L-OHP were significantly different, whether in monotherapy or combined treatment. Primary cell lines needed higher doses to reach IC 50 . There were variations in gene expression among the primary cell lines of different chemosensitivities to the challenge of the same combined dose of 5-FU and L-OHP. The results confirm the heterogeneous nature of colorectal cancer cells from different patient tumors. Studies using primary cancer cells established from patient's tumors rather than secondary cell lines will more closely reflect the actual character of the disease.

A Robust Test of the Unified Model for Seyfert Galaxies with Implications for the Starburst Phenomenon

NASA Technical Reports Server (NTRS)

Weaver, Kimberly A.

1997-01-01

My research involves detailed analysis of X-ray emission from Active Galactic Nuclei (AGN). For over a decade, the paradigm for AGN has rested soundly on the unified model hypothesis, which posits that the only difference between broad-line objects (e.g., Type 1 Seyfert galaxies) and narrow-line objects (e.g., Type 2 Seyferts) is that in the former case our line of sight evades toroidal obscuration surrounding the nucleus, while in the latter, our line of sight is blocked by the optically thick torus. It is well established that some Seyfert 2s contain Seyfert I nuclei (i.e., a hidden broad line region), but whether or not all Seyfert 2s contain obscured Seyfert 1 nuclei or whether some Seyfert 2s are intrinsically Seyfert 2s is not known. Optical, IR, and UV surveys are not appropriate to examine this hypothesis because such emissions are either anisotropic or subject to the effects of obscuration, and thus depend strongly on viewing angle. Hard X-rays, on the other hand, can penetrate gas with column densities as high as 10( exp 24.5) cm(-2) and thus provide reliable, direct probes of the cores of heavily obscured AGN. Combining NASA archival data from the Advanced Satellite of Cosmology and Astrophysics (ASCA), the Rossi X-ray Timing Explorer (RXTE), and Rosat, I am accumulating X-ray data between 0.1 and 60 keV to produce a catalog of the broad-band X-ray spectral properties of Seyfert galaxies. These data will be used to perform concrete tests of the unified model, and (compared with similar data on Starbursts) to examine a possible evolutionary connection between Seyfert and Starburst galaxies.

Installation of C-6533(XE-2)/ARC ICS in UH-1H helicopter

NASA Astrophysics Data System (ADS)

Hnat, J. A.

1980-07-01

This report documents the results of the installation of the C-6533(XE-2)/ARC ICS in UH-1H helicopter. Installation was performed at the AEL, Inc., Monmouth County Airport facility. Design of each installation was coordinated and approved by the Government. The mechanical and electrical installation drawings for the helicopter are attached as Appendix A of this report. The new ICS system consisted of new cabling, new intercoms and helmets rewired with new microphones. All four crew stations of the helicopter were reconfigured with the new system. Existing cabling for the standard ICS system remained in the aircraft but was securely stowed for later restoration of the aircraft. The helmets (4) were rewired using separate jacks for headphones and microphone lines. Transmit and receive cables were installed in the aircraft with a minimum separation of one inch between cables. A junction box was fabricated and installed on the aft end of the console to house the fan-out terminal strips. Transmit and receive lines' separation was maintained in the junction box. During the test phase the onboard radios were used with the new ICS system.

iPTF17cw: An Engine-driven Supernova Candidate Discovered Independent of a Gamma-Ray Trigger

NASA Astrophysics Data System (ADS)

Corsi, A.; Cenko, S. B.; Kasliwal, M. M.; Quimby, R.; Kulkarni, S. R.; Frail, D. A.; Goldstein, A. M.; Blagorodnova, N.; Connaughton, V.; Perley, D. A.; Singer, L. P.; Copperwheat, C. M.; Fremling, C.; Kupfer, T.; Piascik, A. S.; Steele, I. A.; Taddia, F.; Vedantham, H.; Kutyrev, A.; Palliyaguru, N. T.; Roberts, O.; Sollerman, J.; Troja, E.; Veilleux, S.

2017-09-01

We present the discovery, classification, and radio-to-X-ray follow-up observations of iPTF17cw, a broad-lined (BL) type Ic supernova (SN) discovered by the intermediate Palomar Transient Factory (iPTF). Although it is unrelated to the gravitational wave trigger, this SN was discovered as a happy by-product of the extensive observational campaign dedicated to the follow-up of Advanced LIGO event GW 170104. The spectroscopic properties and inferred peak bolometric luminosity of iPTF17cw are most similar to the gamma-ray-burst (GRB)-associated SN, SN 1998bw, while the shape of the r-band light curve is most similar to that of the relativistic SN, SN 2009bb. Karl G. Jansky Very Large Array (VLA) observations of the iPTF17cw field reveal a radio counterpart ≈10 times less luminous than SN 1998bw, and with a peak radio luminosity comparable to that of SN 2006aj/GRB 060218 and SN 2010bh/GRB 100316D. Our radio observations of iPTF17cw imply a relativistically expanding outflow. However, further late-time observations with the VLA in its most extended configuration are needed to confirm fading of the iPTF17cw radio counterpart at all frequencies. X-ray observations carried out with Chandra reveal the presence of an X-ray counterpart with a luminosity similar to that of SN 2010bh/GRB 100316D. Searching the Fermi catalog for possible γ-rays reveals that GRB 161228B is spatially and temporally compatible with iPTF17cw. The similarity to SN 1998bw and SN 2009bb, the radio and X-ray detections, and the potential association with GRB 161228B all point to iPTF17cw being a new candidate member of the rare sample of optically discovered engine-driven BL-Ic SNe associated with relativistic ejecta.

iPTF17cw: An Engine-driven Supernova Candidate Discovered Independent of a Gamma-Ray Trigger

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

Corsi, A.; Palliyaguru, N. T.; Cenko, S. B.

We present the discovery, classification, and radio-to-X-ray follow-up observations of iPTF17cw, a broad-lined (BL) type Ic supernova (SN) discovered by the intermediate Palomar Transient Factory (iPTF). Although it is unrelated to the gravitational wave trigger, this SN was discovered as a happy by-product of the extensive observational campaign dedicated to the follow-up of Advanced LIGO event GW 170104. The spectroscopic properties and inferred peak bolometric luminosity of iPTF17cw are most similar to the gamma-ray-burst (GRB)-associated SN, SN 1998bw, while the shape of the r -band light curve is most similar to that of the relativistic SN, SN 2009bb. Karl G.more » Jansky Very Large Array (VLA) observations of the iPTF17cw field reveal a radio counterpart ≈10 times less luminous than SN 1998bw, and with a peak radio luminosity comparable to that of SN 2006aj/GRB 060218 and SN 2010bh/GRB 100316D. Our radio observations of iPTF17cw imply a relativistically expanding outflow. However, further late-time observations with the VLA in its most extended configuration are needed to confirm fading of the iPTF17cw radio counterpart at all frequencies. X-ray observations carried out with Chandra reveal the presence of an X-ray counterpart with a luminosity similar to that of SN 2010bh/GRB 100316D. Searching the Fermi catalog for possible γ -rays reveals that GRB 161228B is spatially and temporally compatible with iPTF17cw. The similarity to SN 1998bw and SN 2009bb, the radio and X-ray detections, and the potential association with GRB 161228B all point to iPTF17cw being a new candidate member of the rare sample of optically discovered engine-driven BL-Ic SNe associated with relativistic ejecta.« less

Xanthatin and xanthinosin from the burs of Xanthium strumarium L. as potential anticancer agents.

PubMed

Ramírez-Erosa, Irving; Huang, Yaoge; Hickie, Robert A; Sutherland, Ronald G; Barl, Branka

2007-11-01

Xanthatin and xanthinosin, 2 sesquiterpene lactones isolated from the burs of Xanthiun strumarium L. (cocklebur), showed moderate to high in vitro cytotoxic activity in the human cancer cell lines WiDr ATCC (colon), MDA-MB-231 ATCC (breast), and NCI-417 (lung). Xanthatin and xanthinosin were purified as the result of a multi-screening bioassay-guided study of wild plant species of the family Asteraceae, collected from various sites in Saskatchewan, Canada. Seventy-five extracts at a single concentration of 100 microg/mL were evaluated for in vitro cytotoxicity to the human cancer cell lines used. The chloroform extract of Carduus nutans L. (nodding thistle) aerial parts (IC50, 9.3 microg/mL) and the hexane extract of Echinacea angustifolia DC. (narrow-leaved purple coneflower) root (IC50, 4.0 microg/mL) were moderately to highly cytotoxic to the lung cancer cell line. The chloroform extracts of X. strumarium L. burs and Tanacetum vulgare L. (tansy) aerial parts exhibited the highest cytotoxicity for all cell lines tested; their IC50 values, obtained from multidose testing, ranged from 0.1 to 6.2 microg/mL (X. strumarium) and from 2.4 to 9.1 microg/mL (T. vulgare). Further purification of the chloroform fraction of X. strumarium yielded xanthatin and xanthinosin in high yields. This is the first time that these compounds have been reported in the burs of X. strumarium. Their IC50 values are also reported herein.

Cytotoxic steroids from the leaves of Dysoxylum binectariferum.

PubMed

Yan, Hui-Jiao; Wang, Jun-Song; Kong, Ling-Yi

2014-08-01

Four new cholestane-type (1-4) and two new ergostane-type (5, 6) steroids were isolated from the leaves of Dysoxylum binectariferum. Their structures were elucidated on the basis of spectroscopic analysis, including 1D and 2D NMR techniques. The absolute configurations were established by comparison with the literature and Mo2(OAc)4-induced electronic circular dichroism (ECD) data. All the isolates were evaluated for cytotoxicity against A549 (lung carcinoma), MCF-7 (breast adenocarcinoma), and HepG2 (hepatocellular carcinoma) human cancer cell lines. Three of the new cholestane-type steroids displayed potent antiproliferative effects on the tumor cells with IC50 values ranging from 1.5 to 9.6μM, whereas the two new ergostane-type (5, 6) steroids were deemed inactive. Copyright © 2014 Elsevier Inc. All rights reserved.

Dual sensitivity of inferior colliculus neurons to ITD in the envelopes of high-frequency sounds: experimental and modeling study

PubMed Central

Wang, Le; Devore, Sasha; Delgutte, Bertrand

2013-01-01

Human listeners are sensitive to interaural time differences (ITDs) in the envelopes of sounds, which can serve as a cue for sound localization. Many high-frequency neurons in the mammalian inferior colliculus (IC) are sensitive to envelope-ITDs of sinusoidally amplitude-modulated (SAM) sounds. Typically, envelope-ITD-sensitive IC neurons exhibit either peak-type sensitivity, discharging maximally at the same delay across frequencies, or trough-type sensitivity, discharging minimally at the same delay across frequencies, consistent with responses observed at the primary site of binaural interaction in the medial and lateral superior olives (MSO and LSO), respectively. However, some high-frequency IC neurons exhibit dual types of envelope-ITD sensitivity in their responses to SAM tones, that is, they exhibit peak-type sensitivity at some modulation frequencies and trough-type sensitivity at other frequencies. Here we show that high-frequency IC neurons in the unanesthetized rabbit can also exhibit dual types of envelope-ITD sensitivity in their responses to SAM noise. Such complex responses to SAM stimuli could be achieved by convergent inputs from MSO and LSO onto single IC neurons. We test this hypothesis by implementing a physiologically explicit, computational model of the binaural pathway. Specifically, we examined envelope-ITD sensitivity of a simple model IC neuron that receives convergent inputs from MSO and LSO model neurons. We show that dual envelope-ITD sensitivity emerges in the IC when convergent MSO and LSO inputs are differentially tuned for modulation frequency. PMID:24155013

Naphthoquinones from the leaves of Rhinacanthus nasutus having acetylcholinesterase inhibitory and cytotoxic activities.

PubMed

Boonyaketgoson, Sirada; Rukachaisirikul, Vatcharin; Phongpaichit, Souwalak; Trisuwan, Kongkiat

2018-01-01

Four new naphthoquinones (1-4), named rhinacanthins S (1), T (2), U (3) and V (4), together with 13 known naphthoquinones were isolated from the leaf extract of Rhinacanthus nasutus. The structures of isolated compounds were elucidated by spectroscopic methods, especially 1D and 2D NMR spectroscopy and mass spectrometry. Rhinacanthin S (1) exhibited acetylcholinesterase inhibition activity with a % inhibition value of 48.04±3.25. The known rhinacanthin A (5) showed cytotoxicity against a MCF-7 cell line with an IC 50 value of 8.79μM, while rhinacanthin N (15) was active against the NCI-H187 cell line with an IC 50 =2.24μM and Vero cells (IC 50 =3.00μM). Copyright © 2017 Elsevier B.V. All rights reserved.

Synthesis and Characterization of New Palladium(II) Thiosemicarbazone Complexes and Their Cytotoxic Activity against Various Human Tumor Cell Lines

PubMed Central

Hernández, Wilfredo; Paz, Juan; Carrasco, Fernando; Spodine, Evgenia; Manzur, Jorge; Sieler, Joachim; Blaurock, Steffen; Beyer, Lothar

2013-01-01

The palladium(II) bis-chelate complexes of the type [Pd(TSC1-5)2] (6–10), with their corresponding ligands 4-phenyl-1-(acetone)-thiosemicarbazone, HTSC1 (1), 4-phenyl-1-(2′-chloro-benzaldehyde)-thiosemicarbazone, HTSC2 (2), 4-phenyl-1-(3′-hydroxy-benzaldehyde)-thiosemicarbazone, HTSC3 (3), 4-phenyl-1-(2′-naphthaldehyde)-thiosemicarbazone, HTSC4 (4), and 4-phenyl-1-(1′-nitro-2′-naphthaldehyde)-thiosemicarbazone, HTSC5 (5), were synthesized and characterized by elemental analysis and spectroscopic techniques (IR and 1H- and 13C-NMR). The molecular structure of HTSC3, HTSC4, and [Pd(TSC1)2] (6) have been determined by single crystal X-ray crystallography. Complex 6 shows a square planar geometry with two deprotonated ligands coordinated to PdII through the azomethine nitrogen and thione sulfur atoms in a cis arrangement. The in vitro cytotoxic activity measurements indicate that the palladium(II) complexes (IC50 = 0.01–9.87 μM) exhibited higher antiproliferative activity than their free ligands (IC50 = 23.48–70.86 and >250 μM) against different types of human tumor cell lines. Among all the studied palladium(II) complexes, the [Pd(TSC3)2] (8) complex exhibited high antitumor activity on the DU145 prostate carcinoma and K562 chronic myelogenous leukemia cells, with low values of the inhibitory concentration (0.01 and 0.02 μM, resp.). PMID:24391528

Physical Properties of the Very Young PN Hen3-1357 (Stingray Nebula) Based on Multiwavelength Observations

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

Otsuka, Masaaki; Parthasarathy, M.; Tajitsu, A.

We carried out a detailed analysis of the interesting and important very young planetary nebula (PN) Hen3-1357 (Stingray Nebula) based on a unique data set of optical to far-IR spectra and photometric images. We calculated the abundances of nine elements using collisionally excited lines (CELs) and recombination lines (RLs). The RL C/O ratio indicates that this PN is O-rich, which is also supported by the detection of the broad 9/18 μ m bands from amorphous silicate grains. The observed elemental abundances can be explained by asymptotic giant branch (AGB) nucleosynthesis models for initially 1–1.5 M {sub ⊙} stars with Zmore » = 0.008. The Ne overabundance might be due to the enhancement of {sup 22}Ne isotope in the He-rich intershell. Using the spectrum of the central star synthesized by Tlusty as the ionization/heating source of the PN, we constructed the self-consistent photoionization model with Cloudy to the observed quantities and derived the gas and dust masses, dust-to-gas mass ratio, and core mass of the central star. About 80% of the total dust mass is from warm–cold dust component beyond ionization front. Comparison with other Galactic PNe indicates that Hen3-1357 is an ordinary amorphous silicate-rich and O-rich gas PN. Among other studied PNe, IC4846 shows many similarities in properties of the PN to Hen3-1357, although their post-AGB evolution is quite different from each other. Further monitoring of observations and comparisons with other PNe such as IC4846 are necessary to understand the evolution of Hen3-1357.« less

Emission Line Properties of Seyfert Galaxies in the 12 μm Sample

NASA Astrophysics Data System (ADS)

Malkan, Matthew A.; Jensen, Lisbeth D.; Rodriguez, David R.; Spinoglio, Luigi; Rush, Brian

2017-09-01

We present optical and ultraviolet spectroscopic measurements of the emission lines of 81 Seyfert 1 and 104 Seyfert 2 galaxies that comprise nearly all of the IRAS 12 μm AGN sample. We have analyzed the emission-line luminosity functions, reddening, and other diagnostics. For example, the narrow-line regions (NLR) of Seyfert 1 and 2 galaxies do not significantly differ from each other in most of these diagnostics. Combining the Hα/Hβ ratio with a new reddening indicator—the [S II]6720/[O II]3727 ratio—we find the average E(B-V) is 0.49 ± 0.35 for type 1 and 0.52 ± 0.26 for type 2 Seyferts. The NLR of Sy 1s has an ionization level insignificantly higher than that of Sy 2s. For the broad-line region (BLR), we find that the C IV equivalent width correlates more strongly with [O III]/Hβ than with UV luminosity. Our bright sample of local active galaxies includes 22 Seyfert nuclei with extremely weak broad wings in Hα, known as Seyfert 1.9s and 1.8s, depending on whether or not broad Hβ wings are detected. Aside from these weak broad lines, our low-luminosity Seyferts are more similar to the Sy 2s than to Sy 1s. In a BPT diagram, we find that Sy 1.8s and 1.9s overlap the region occupied by Sy 2s. We compare our results on optical emission lines with those obtained by previous investigators, using AGN subsamples from the Sloan Digital Sky Survey. The luminosity functions of forbidden emission lines [O II]λ3727 Å, [O III]λ5007 Å, and [S II]λ6720 Å in Sy 1s and Sy 2s are indistinguishable. They all show strong downward curvature. Unlike the LFs of Seyfert galaxies measured by the Sloan Digital Sky Survey, ours are nearly flat at low luminosities. The larger number of faint Sloan “AGN” is attributable to their inclusion of weakly emitting LINERs and H II+AGN “composite” nuclei, which do not meet our spectral classification criteria for Seyferts. In an Appendix, we have investigated which emission line luminosities can provide the most reliable measures of the total non-stellar luminosity, estimated from our extensive multi-wavelength database. The hard X-ray or near-ultraviolet continuum luminosity can be crudely predicted from either the [O III]λ5007 Å luminosity or the combinations of [O III]+Hβ or [N II]+Hα lines, with a scatter of +/- 4 times for Sy 1s and +/- 10 times for Sy 2s. Although these uncertainties are large, the latter two hybrid (NLR+BLR) indicators have the advantage of predicting the same HX luminosity independent of Seyfert type.

Different regions of line formation in the envelope of the early emission line star HD 190073

NASA Technical Reports Server (NTRS)

Ringuelet, A. E.; Rovira, M.; Cidale, L.; Sahade, J.

1987-01-01

A description is presented of the spectral features that characterize the spectrum of HD 190073 both in the photographic region (360-660 nm), and in the IUE UV (115-320 nm). A number of different types of profiles can be distinguished, and this seems to imply that many different 'broad' regions of line formation coexist in the extended envelope of the star, including regions with densities differing in several orders of magnitude.

The effects of tumor treating fields and temozolomide in MGMT expressing and non-expressing patient-derived glioblastoma cells.

PubMed

Clark, Paul A; Gaal, Jordan T; Strebe, Joslyn K; Pasch, Cheri A; Deming, Dustin A; Kuo, John S; Robins, H Ian

2017-02-01

A recent Phase 3 study of newly diagnosed glioblastoma (GBM) demonstrated the addition of tumor treating fields (TTFields) to temozolomide (TMZ) after combined radiation/TMZ significantly increased survival and progression free survival. Preliminary data suggested benefit with both methylated and unmethylated O-6-methylguanine-DNA methyl-transferase (MGMT) promoter status. To date, however, there have been no studies to address the potential interactions of TTFields and TMZ. Thus, the effects of TTFields and TMZ were studied in vitro using patient-derived GBM stem-like cells (GSCs) including MGMT expressing (TMZ resistant: 12.1 and 22GSC) and non-MGMT expressing (TMZ sensitive: 33 and 114GSC) lines. Dose-response curves were constructed using cell proliferation and sphere-forming assays. Results demonstrated a ⩾10-fold increase in TMZ resistance of MGMT-expressing (12.1GSCs: IC 50 =160μM; 22GSCs: IC 50 =44μM) compared to MGMT non-expressing (33GSCs: IC 50 =1.5μM; 114GSCs: IC 50 =5.2μM) lines. TTFields inhibited 12.1 GSC proliferation at all tested doses (50-500kHz) with an optimal frequency of 200kHz. At 200kHz, TTFields inhibited proliferation and tumor sphere formation of both MGMT GSC subtypes at comparable levels (12.1GSC: 74±2.9% and 38±3.2%, respectively; 22GSC: 61±11% and 38±2.6%, respectively; 33GSC: 56±9.5% and 60±7.1%, respectively; 114 GSC: 79±3.5% and 41±4.3%, respectively). In combination, TTFields (200kHz) and TMZ showed an additive anti-neoplastic effect with equal efficacy for TTFields in both cell types (i.e., ± MGMT expression) with no effect on TMZ resistance. This is the first demonstration of the effects of TTFields on cancer stem cells. The expansion of such studies may have clinical implications. Copyright © 2016 Elsevier Ltd. All rights reserved.

The Effects of Tumor Treating Fields and Temozolomide in MGMT Expressing and Non-Expressing Patient-Derived Glioblastoma Cells

PubMed Central

Clark, Paul A.; Gaal, Jordan T; Strebe, Joslyn K.; Pasch, Cheri A; Deming, Dustin A; Kuo, John S.; Robins, H. Ian

2016-01-01

A recent Phase 3 study of newly diagnosed glioblastoma (GBM) demonstrated the addition of Tumor Treating Fields (TTFields) to temozolomide (TMZ) after combined radiation/TMZ significantly increased survival and progression free survival. Preliminary data suggested benefit with both methylated and unmethylated O-6-methylguanine-DNA methyl-transferase (MGMT) promoter status. To date, however, there have been no studies to address the potential interactions of TTFields and TMZ. Thus, the effects of TTFields and TMZ were studied in vitro using patient-derived GBM stem-like cells (GSCs) including MGMT expressing (TMZ resistant:12.1 and 22 GSC) and non-MGMT expressing (TMZ sensitive:33 and 114 GSC) lines. Dose-response curves were constructed using cell proliferation and sphere-forming assays. Results demonstrated a ≥10-fold increase in TMZ resistance of MGMT-expressing (12.1 GSCs: IC50=160 μM; 22 GSCs: IC50=44 μM) compared to MGMT non-expressing (33 GSCs: IC50=1.5 μM; 114 GSCs: IC50=5.2 μM) lines. TTFields inhibited 12.1 GSC proliferation at all tested doses (50-500 kHz) with an optimal frequency of 200 kHz. At 200 kHz, TTFields inhibited proliferation and tumor sphere formation of both MGMT GSC subtypes at comparable levels (12.1 GSC: 74±2.9% and 38±3.2%, respectively; 22 GSC: 61±11% and 38±2.6%, respectively; 33 GSC: 56±9.5% and 60±7.1%, respectively; 114 GSC: 79± 3.5% and 41±4.3%, respectively). In combination, TTFields (200 kHz) and TMZ showed an additive anti-neoplastic effect with equal efficacy for TTFields in both cell types (i.e., +/- MGMT expression) with no effect on TMZ resistance. This is the first demonstration of the effects of TTFields on cancer stem cells. The expansion of such studies may have clinical implications. PMID:27865821

Two distinct HLA-A0201-presented epitopes of the Wilms tumor antigen 1 can function as targets for leukemia-reactive CTL.

PubMed

Bellantuono, Ilaria; Gao, Liquan; Parry, Suzanne; Marley, Steve; Dazzi, Francesco; Apperley, Jane; Goldman, John M; Stauss, Hans J

2002-11-15

Using the allo-restricted T-cell approach to circumvent tolerance, we have previously identified a cytotoxic T-lymphocyte (CTL) epitope in the transcription factor Wilms tumor antigen 1 (WT1) presented by HLA-A0201 (A2) class I molecules. Here we describe an additional A2-presented epitope and show that CTLs against both epitopes kill WT1-expressing leukemia cell lines. Colony-forming assays demonstrated that both types of CTL killed CD34(+) progenitor cells from A2(+) leukemia patients, but not from A2(+) healthy individuals. The long-term culture-initiating cell (LTC-IC) assay was used to analyze the killing activity of WT1-specific CTLs against the more immature fraction of CD34(+) cells. The CTLs killed LTC-ICs of patients with chronic myelogenous leukemia (CML), whereas the function of normal CD34(+) progenitor/stem cells was not inhibited. Together, the data show that CTLs specific for 2 distinct peptide epitopes of WT1 can discriminate between normal and leukemia LTC-ICs, suggesting that such CTLs have the potential to selectively kill CML progenitor/stem cells.

Influence of in vivo growth on human glioma cell line gene expression: Convergent profiles under orthotopic conditions

PubMed Central

Camphausen, Kevin; Purow, Benjamin; Sproull, Mary; Scott, Tamalee; Ozawa, Tomoko; Deen, Dennis F.; Tofilon, Philip J.

2005-01-01

Defining the molecules that regulate tumor cell survival is an essential prerequisite for the development of targeted approaches to cancer treatment. Whereas many studies aimed at identifying such targets use human tumor cells grown in vitro or as s.c. xenografts, it is unclear whether such experimental models replicate the phenotype of the in situ tumor cell. To begin addressing this issue, we have used microarray analysis to define the gene expression profile of two human glioma cell lines (U251 and U87) when grown in vitro and in vivo as s.c. or as intracerebral (i.c.) xenografts. For each cell line, the gene expression profile generated from tissue culture was significantly different from that generated from the s.c. tumor, which was significantly different from those grown i.c. The disparity between the i.c gene expression profiles and those generated from s.c. xenografts suggests that whereas an in vivo growth environment modulates gene expression, orthotopic growth conditions induce a different set of modifications. In this study the U251 and U87 gene expression profiles generated under the three growth conditions were also compared. As expected, the profiles of the two glioma cell lines were significantly different when grown as monolayer cultures. However, the glioma cell lines had similar gene expression profiles when grown i.c. These results suggest that tumor cell gene expression, and thus phenotype, as defined in vitro is affected not only by in vivo growth but also by orthotopic growth, which may have implications regarding the identification of relevant targets for cancer therapy. PMID:15928080

The Interstellar 7Li/6Li Ratio in the Diffuse Gas Near IC 443

NASA Astrophysics Data System (ADS)

Ritchey, A. M.; Taylor, C. J.; Federman, S. R.; Lambert, D. L.

2010-11-01

Supernova remnants are believed to be the primary acceleration sites of Galactic cosmic rays (GCR), which are essential to gas-phase interstellar chemistry since they are a major source of ionization in both diffuse and dense environments. The interaction of accelerated particles with interstellar gas will also synthesize isotopes of the light elements Li, Be, and B through the spallation of CNO nuclei (producing all stable LiBeB isotopes) and through α+α fusion (yielding 6Li and 7Li, only). Type II supernovae may provide an additional source of 7Li and 11B during core collapse through neutrino-induced spallation in the He and C shells of the progenitor star (the ν-process). However, direct observational evidence for light element synthesis resulting from cosmic-ray or neutrino-induced spallation is rare. Here, we examine 7Li/6Li isotope ratios along four lines of sight through the supernova remnant IC 443 using observations of the Li I λ6707 doublet made with the Hobby-Eberly Telescope (HET) at McDonald Observatory. The 7Li/6Li ratio in the general interstellar medium is expected to be similar to the ratio of ~12 that characterizes solar system material. A local enhancement in the cosmic-ray flux will act to lower 7Li/6Li, yielding a ratio of ~2 when cosmic rays dominate Li synthesis. Gamma-ray emission from IC 443 provides strong evidence for the interaction of cosmic rays accelerated by the remnant with the ambient atomic and molecular gas. Yet this material has also been contaminated by the ejecta of a Type II supernova, which should be enriched in 7Li. We are seeking 7Li/6Li ratios that are either higher than the solar system ratio as a result of the ν-process or lower due to cosmic-ray spallation. Since the fine structure separation of the Li I doublet is comparable to the isotope shift (~7 km s-1) and each fine structure line is further split into hyperfine components, the velocity structure along the line of sight must be carefully constrained if meaningful 7Li/6Li ratios are to be determined. In our analysis, the strongest components seen in K I and CH are used to synthesize the complex Li I profiles. We will discuss the implications of our results on 7Li/6Li (and Li/K) ratios in the context of Li production by Type II supernovae.

High-resolution spectroscopy of the extended narrow-line region of IC 5063 and NGC 7212

NASA Astrophysics Data System (ADS)

Congiu, E.; Contini, M.; Ciroi, S.; Cracco, V.; Berton, M.; Di Mille, F.; Frezzato, M.; La Mura, G.; Rafanelli, P.

2017-10-01

We studied the properties of the gas of the extended narrow-line region (ENLR) of two Seyfert 2 galaxies: IC 5063 and NGC 7212. We analysed high-resolution spectra to investigate how the main properties of this region depend on the gas velocity. We divided the emission lines in velocity bins and we calculated several line ratios. Diagnostic diagrams and suma composite models (photoionization + shocks) show that in both galaxies there might be evidence of shocks significantly contributing in the gas ionization at high |V|, even though photoionization from the active nucleus remains the main ionization mechanism. In IC 5063, the ionization parameter depends on V and its trend might be explained assuming an hollow bi-conical shape for the ENLR, with one of the edges aligned with the galaxy disc. On the other hand, NGC 7212 does not show any kind of dependence. The models show that solar O/H relative abundances reproduce the observed spectra in all the analysed regions. They also revealed an high fragmentation of the gas clouds, suggesting that the complex kinematics observed in these two objects might be caused by interaction between the interstellar medium and high-velocity components, such as jets.

Cyclopentenone derivatives and polyhydroxylated steroids from the soft coral Sinularia acuta.

PubMed

Zhang, Nai-Xia; Tang, Xu-Li; van Ofwegen, Leen; Xue, Lei; Song, Wen-Juan; Li, Ping-Lin; Li, Guo-Qiang

2015-02-01

Four new polyhydroxylated steroids, 1-4, and the racemic form of cyclopentenone 9, together with four known steroids, 5-8, one known cyclopentenone derivative, 10, and one known butenolide derivative, 11, were isolated from the soft coral Sinularia acuta collected from Weizhou Island of Guangxi Province, P. R. China. Their structures were elucidated on the basis of spectroscopic analyses and by comparison of the corresponding data with those previously reported. The cytotoxicities of the isolates 1-11 in vitro against the selected tumor cell lines HL-60, HeLa, and K562 were evaluated. Compounds 2 and 5 showed potent cytotoxicities against HL-60 cell lines with IC50 values of 7.3 and 9.9 μM, respectively. Compounds 5 and 6 showed moderate activities against K562 cell lines with IC50 values of 10.9 and 11.7 μM, respectively, while compounds 1, 2, and 6 showed weak activities against HeLa cell lines with respective IC50 values of 44.8, 27.1, and 18.2 μM. This is the first report on chemical and bioactivity research of S. acuta. Copyright © 2015 Verlag Helvetica Chimica Acta AG, Zürich.

Space Density Of Optically-Selected Type II Quasars From The SDSS

NASA Astrophysics Data System (ADS)

Reyes, Reinabelle; Zakamska, N. L.; Strauss, M. A.; Green, J.; Krolik, J. H.; Shen, Y.; Richards, G. T.

2007-12-01

Type II quasars are luminous Active Galactic Nuclei (AGN) whose central regions are obscured by large amounts of gas and dust. In this poster, we present a catalog of 887 type II quasars with redshifts z<0.83 from the Sloan Digital Sky Survey (SDSS), selected based on their emission lines, and derive the 1/Vmax [OIII] 5007 luminosity function from this sample. Since some objects may not be included in the sample because they lack strong emission lines, the derived luminosity function is only a lower limit. We also derive the [OIII] 5007 luminosity function for a sample of type I (broad-line) quasars in the same redshift range. Taking [OIII] 5007 luminosity as a tracer of intrinsic luminosity in both type I and type II quasars, we obtain lower limits to the type II quasar fraction as a function of [OIII] 5007 luminosity, from L[OIII] = 108.3 to 1010 Lsun, which roughly correspond to bolometric luminosities of 1044 to 1046 erg/s.

The Distribution of Wolf-Rayet Stars in NGC 6744

NASA Astrophysics Data System (ADS)

Sandford, Emily; Bibby, J. L.; Zurek, D.; Crowther, P.

2013-01-01

We undertake a survey of the Wolf-Rayet population of NGC 6744, a spiral galaxy located at an estimated distance of 11.6 Mpc, in order to determine whether the distribution of this population is consistent with the distributions of various ccSNe subtypes. 242 Wolf-Rayet candidate sources are identified, 40% of which are only detected in narrow-band helium II imaging, not in broad-band imaging. The spatial distribution of WR candidates is compared to the distributions of ccSNe subtype populations in the broad-band B filter and the narrow-band Hα filter. WR stars appear to follow the Type Ic distribution in the faintest 30% of the galaxy in the B image, but follow the Ib or II distribution in the brightest regions, possibly due to the difficulty of detecting WR stars in the brightest regions. WR candidates are found to be closely associated with HII regions; however, the treatment of the residual background strongly affects the distribution, and this result must be investigated further.

78 FR 23633 - Union Pacific Railroad Company-Trackage Rights Exemption-Illinois Central Railroad Company

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-19

... Railroad Company--Trackage Rights Exemption-- Illinois Central Railroad Company Illinois Central Railroad... trackage rights to Union Pacific Railroad Company (UP) over IC's Chicago Subdivision between milepost 21.0... predecessor railroads, it currently maintains trackage rights over approximately 60 miles of IC's rail line...

Novel microtubule-targeted agent 6-chloro-4-(methoxyphenyl) coumarin induces G2-M arrest and apoptosis in HeLa cells

PubMed Central

Ma, Yi-ming; Zhou, Yu-bo; Xie, Chuan-ming; Chen, Dong-mei; Li, Jia

2012-01-01

Aim: To identify a novel coumarin analogue with the highest anticancer activity and to further investigate its anticancer mechanisms. Methods: The viability of cancer cells was investigated using the MTT assay. The cell cycle progression was evaluated using both flow cytometric and Western blotting analysis. Microtubule depolymerization was observed with immunocytochemistry in vivo and a tubulin depolymerization assay in vitro. Apoptosis was demonstrated using Annexin V/Propidium Iodide (PI) double-staining and sub-G1 analysis. Results: Among 36 analogues of coumarin, 6-chloro-4-(methoxyphenyl) coumarin showed the best anticancer activity (IC50 value about 200 nmol/L) in HCT116 cells. The compound had a broad spectrum of anticancer activity against 9 cancer cell lines derived from colon cancer, breast cancer, liver cancer, cervical cancer, leukemia, epidermoid cancer with IC50 value of 75 nmol/L–1.57 μmol/L but with low cytotocitity against WI-38 human lung fibroblasts (IC50 value of 12.128 μmol/L). The compound (0.04–10 μmol/L) induced G2-M phase arrest in HeLa cells in a dose-dependent manner, which was reversible after the compound was removed. The compound (10–300 μmol/L) induced the depolymerization of purified porcine tubulin in vitro. Finally, the compound (0.04–2.5 μmol/L) induced apoptosis of HeLa cells in dose- and time-dependent manners. Conclusion: 6-Chloro-4-(methoxyphenyl) coumarin is a novel microtubule-targeting agent that induces G2–M arrest and apoptosis in HeLa cells. PMID:22266726

High-redshift Blazars through NuSTAR eyes

DOE PAGES

Marcotulli, L.; Paliya, V. S.; Ajello, M.; ...

2017-04-20

The most powerful sources among the blazar family are MeV blazars. Often detected at z > 2, they usually display high X- and γ-ray luminosities, larger-than-average jet powers, and black hole masses ≳10 9 M ⊙. In the present work, we perform a multiwavelength study of three high-redshift blazars: 3FGL J0325.5+2223 (z = 2.06), 3FGL J0449.0+1121 (z = 2.15), and 3FGL J0453.2–2808 (z = 2.56), analyzing quasi-simultaneous data from GROND, Swift-UVOT and XRT, Nuclear Spectroscopic Telescope Array (NuSTAR), and Fermi-LAT. Our main focus is on the hard X-ray band recently unveiled by NuSTAR (3–79 keV) where these objects show amore » hard spectrum that enables us to constrain the inverse Compton (IC) peak and the jet power. We found that all three targets resemble the most powerful blazars, with the synchrotron peak located in the submillimeter range and the IC peak in the MeV range, and therefore belong to the MeV blazar class. Using a simple one-zone leptonic emission model to reproduce the spectral energy distributions, we conclude that a simple combination of synchrotron and accretion disk emission reproduces the infrared–optical spectra, while the X-ray to γ-ray part is well reproduced by the IC scattering of low-energy photons supplied by the broad-line region. The black hole masses for each of the three sources are calculated to be ≳4 × 10 8 M ⊙. Finally, the three studied sources have jet power at the level of, or beyond, the accretion luminosity.« less

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

Marcotulli, L.; Paliya, V. S.; Ajello, M.

The most powerful sources among the blazar family are MeV blazars. Often detected at z > 2, they usually display high X- and γ -ray luminosities, larger-than-average jet powers, and black hole masses ≳10{sup 9} M {sub ☉}. In the present work, we perform a multiwavelength study of three high-redshift blazars: 3FGL J0325.5+2223 ( z = 2.06), 3FGL J0449.0+1121 ( z = 2.15), and 3FGL J0453.2−2808 ( z = 2.56), analyzing quasi-simultaneous data from GROND, Swift -UVOT and XRT, Nuclear Spectroscopic Telescope Array ( NuSTAR ), and Fermi -LAT. Our main focus is on the hard X-ray band recently unveiledmore » by NuSTAR (3–79 keV) where these objects show a hard spectrum that enables us to constrain the inverse Compton (IC) peak and the jet power. We found that all three targets resemble the most powerful blazars, with the synchrotron peak located in the submillimeter range and the IC peak in the MeV range, and therefore belong to the MeV blazar class. Using a simple one-zone leptonic emission model to reproduce the spectral energy distributions, we conclude that a simple combination of synchrotron and accretion disk emission reproduces the infrared–optical spectra, while the X-ray to γ -ray part is well reproduced by the IC scattering of low-energy photons supplied by the broad-line region. The black hole masses for each of the three sources are calculated to be ≳4 × 10{sup 8} M {sub ☉}. The three studied sources have jet power at the level of, or beyond, the accretion luminosity.« less

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

Marcotulli, L.; Paliya, V. S.; Ajello, M.

The most powerful sources among the blazar family are MeV blazars. Often detected at z > 2, they usually display high X- and γ-ray luminosities, larger-than-average jet powers, and black hole masses ≳10 9 M ⊙. In the present work, we perform a multiwavelength study of three high-redshift blazars: 3FGL J0325.5+2223 (z = 2.06), 3FGL J0449.0+1121 (z = 2.15), and 3FGL J0453.2–2808 (z = 2.56), analyzing quasi-simultaneous data from GROND, Swift-UVOT and XRT, Nuclear Spectroscopic Telescope Array (NuSTAR), and Fermi-LAT. Our main focus is on the hard X-ray band recently unveiled by NuSTAR (3–79 keV) where these objects show amore » hard spectrum that enables us to constrain the inverse Compton (IC) peak and the jet power. We found that all three targets resemble the most powerful blazars, with the synchrotron peak located in the submillimeter range and the IC peak in the MeV range, and therefore belong to the MeV blazar class. Using a simple one-zone leptonic emission model to reproduce the spectral energy distributions, we conclude that a simple combination of synchrotron and accretion disk emission reproduces the infrared–optical spectra, while the X-ray to γ-ray part is well reproduced by the IC scattering of low-energy photons supplied by the broad-line region. The black hole masses for each of the three sources are calculated to be ≳4 × 10 8 M ⊙. Finally, the three studied sources have jet power at the level of, or beyond, the accretion luminosity.« less

Pharmacologically significant complexes of Mn(II), Co(II), Ni(II), Cu(II) and Zn(II) of novel Schiff base ligand, (E)-N-(furan-2-yl methylene) quinolin-8-amine: Synthesis, spectral, XRD, SEM, antimicrobial, antioxidant and in vitro cytotoxic studies

NASA Astrophysics Data System (ADS)

Shakir, M.; Hanif, Summaiya; Sherwani, Mohd. Asif; Mohammad, Owais; Al-Resayes, Saud I.

2015-07-01

A novel series of metal complexes of the types, [ML2(H2O)2]Cl2 and [ML2]Cl2 [M = Mn(II), 1; Co(II), 2; Ni(II), 3; Cu(II), 4; and Zn(II), 5] were synthesized by the interaction of ligand, L (E)-N-(furan-2-yl methylene) quinolin-8-amine, derived from the condensation of 2-furaldehyde and 8-aminoquinoline. The synthesized ligand and its metal complexes were characterized on the basis of results obtained from elemental analysis, ESI-MS, XRD, SEM, TGA/DTA, FT-IR, UV-Vis, magnetic moment and 1H and 13C NMR spectroscopic studies. EPR parameters were recorded in case of complex 4. The comparative in-vitro antimicrobial activities against various pathogens with reference to known antibiotics and antioxidant activity against standard control at variable concentrations revealed that the metal complexes show enhanced antimicrobial and free radical scavenging activities in general as compared to free ligand. However, the complexes 1 and 5 have shown best antioxidant activity among all the metal complexes. Furthermore, comparative in-vitro antiproliferative activity on ligand and its metal chelates performed on MDA-MB-231 (breast carcinoma), KCL22 (blood lymphoid carcinoma), HeLa (cervical carcinoma) cell lines and normal cells (PBMC) revealed that metal chelates show moderate to good activity as compared to ligand where as complex 1 seems to be the most promising one possessing a broad spectrum of activity against all the selected cancer cell lines with IC50 < 2.10 μM.

EVIDENCE THAT GAMMA-RAY BURST 130702A EXPLODED IN A DWARF SATELLITE OF A MASSIVE GALAXY

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

Kelly, Patrick L.; Filippenko, Alexei V.; Fox, Ori D.

2013-09-20

GRB 130702A is a nearby long-duration gamma-ray burst (LGRB) discovered by the Fermi satellite whose associated afterglow was detected by the Palomar Transient Factory. Subsequent photometric and spectroscopic monitoring has identified a coincident broad-lined Type Ic supernova (SN), and nebular emission detected near the explosion site is consistent with a redshift of z = 0.145. The SN-GRB exploded at an offset of {approx}7.''6 from the center of an inclined r = 18.1 mag red disk-dominated galaxy, and {approx}0.''6 from the center of a much fainter r = 23 mag object. We obtained Keck-II DEIMOS spectra of the two objects andmore » find a 2{sigma} upper limit on their line-of-sight velocity offset of {approx}<60 km s{sup -1}. If we calculate the inclination angle of the massive red galaxy from its axis ratio and assume that its light is dominated by a very thin disk, the explosion would have a {approx}60 kpc central offset, or {approx}9 times the galaxy's half-light radius. A significant bulge or a thicker disk would imply a higher inclination angle and greater central offset. The substantial offset suggests that the faint source is a separate dwarf galaxy. The star-formation rate of the dwarf galaxy is {approx}0.05 M{sub Sun} yr{sup -1}, and we place an upper limit on its oxygen abundance of 12 + log(O/H) < 8.16 dex. The identification of an LGRB in a dwarf satellite of a massive, metal-rich primary galaxy suggests that recent detections of LGRBs spatially coincident with metal-rich galaxies may be, in some cases, superpositions.« less

A cationic amphiphilic peptide ABP-CM4 exhibits selective cytotoxicity against leukemia cells.

PubMed

Chen, Yu Qing; Min, Cui; Sang, Ming; Han, Yang Yang; Ma, Xiao; Xue, Xiao Qing; Zhang, Shuang Quan

2010-08-01

Some cationic antibacterial peptides exhibit a broad spectrum of cytotoxic activity against cancer cells, which could provide a new class of anticancer drugs. In the present study, the anticancer activity of ABP-CM4, an antibacterial peptide from Bombyx mori, against leukemic cell lines THP-1, K562 and U937 was evaluated, and the cytotoxicity compared with the effects on non-cancerous mammalian cells, including peripheral blood mononuclear cells (PBMCs), HEK-293 and erythrocytes. ABP-CM4 reduced the number of viable cells of the leukemic cell lines after exposure for 24h. The reduction was concentration dependent, and the IC50 values ranged from 14 to 18 microM. Conversely, ABP-CM4, even at 120 microM, exhibited no cytotoxicity toward HEK-293 or PBMCs, indicating that there was no significant effect on these two types of non-cancer cells. ABP-CM4 at a concentration of 200 microM had no hemolytic activity on mammalian erythrocytes. Together, these results suggested a selective cytotoxicity in leukemia cells. Flow cytometry demonstrated that the binding activity of ABP-CM4 to leukemia cells was much higher than that to HEK-293 or PBMCs, and there was almost no binding to erythrocytes. FITC-labeled ABP-CM4 molecules were examined under a confocal microscope and found to be concentrated at the surface of leukemia cells and changes of the cell membrane were determined by a cell permeability assay, which led us to the conclusion that ABP-CM4 could act at the cell membrane for its anticancer activity on leukemia cells. Collectively, our results indicated that ABP-CM4 has the potential for development as a novel antileukemic agent. Copyright 2010 Elsevier Inc. All rights reserved.

Monoalkylated barbiturate derivatives: X-ray crystal structure, theoretical studies, and biological activities

NASA Astrophysics Data System (ADS)

Barakat, Assem; Al-Majid, Abdullah Mohammed; Soliman, Saied M.; Islam, Mohammad Shahidul; Ghawas, Hussain Mansur; Yousuf, Sammer; Choudhary, M. Iqbal; Wadood, Abdul

2017-08-01

Barbiturate derivatives are privileged structures with a broad range of pharmaceutical applications. We prepared a series of 5-monoalkylated barbiturate derivatives (3a-l) and evaluated, in vitro, their antioxidant (DPPH assay), and α-glucosidase inhibitory activities. Compounds 3a-l were synthesized via Michael addition. The structure of compound 3k was determined using X-ray single-crystal diffraction, and geometric parameters were calculated using density functional theory at the B3LYP/6-311G(d,p) level of theory. Further, the structural analysis of 3k were also investigated. Biological studies revealed that compounds 3b (IC50 = 133.1 ± 3.2 μM), 3d (IC50 = 305 ± 7.7 μM), and 3e (IC50 = 184 ± 2.3 μM) have potent α-glucosidase enzyme inhibitors and showed greater activity than the standard drug acarbose (IC50 = 841 ± 1.73 μM). Compounds 3a-3i were found to show weak antioxidant activity against 1,1-diphenyl-2-picryl-hydrazyl (DPPH) radicals (IC50 = 91 ± 0.75 to 122 ± 1.0 μM) when tested against a standard antioxidant, gallic acid (IC50 = 23 ± 0.43 μM).

The nature of 50 Palermo Swift-BAT hard X-ray objects through optical spectroscopy

NASA Astrophysics Data System (ADS)

Rojas, A. F.; Masetti, N.; Minniti, D.; Jiménez-Bailón, E.; Chavushyan, V.; Hau, G.; McBride, V. A.; Bassani, L.; Bazzano, A.; Bird, A. J.; Galaz, G.; Gavignaud, I.; Landi, R.; Malizia, A.; Morelli, L.; Palazzi, E.; Patiño-Álvarez, V.; Stephen, J. B.; Ubertini, P.

2017-06-01

We present the nature of 50 hard X-ray emitting objects unveiled through an optical spectroscopy campaign performed at seven telescopes in the northern and southern hemispheres. These objects were detected with the Burst Alert Telescope (BAT) instrument onboard the Swift satellite and listed as of unidentified nature in the 54-month Palermo BAT catalogue. In detail, 45 sources in our sample are identified as active galactic nuclei of which, 27 are classified as type 1 (with broad and narrow emission lines) and 18 are classified as type 2 (with only narrow emission lines). Among the broad-line emission objects, one is a type 1 high-redshift quasi-stellar object, and among the narrow-line emission objects, one is a starburst galaxy, one is a X-ray bright optically normal galaxy, and one is a low ionization nuclear emission line region. We report 30 new redshift measurements, 13 confirmations and 2 more accurate redshift values. The remaining five objects are galactic sources: three are Cataclismic Variables, one is a X-ray Binary probably with a low mass secondary star, and one is an active star. Based on observations obtained from the following observatories: Cerro Tololo Interamerican Observatory (Chile); Astronomical Observatory of Bologna in Loiano (Italy); Observatorio Astronómico Nacional (San Pedro Mártir, Mexico); Radcliffe telescope of the South African Astronomical Observatory (Sutherland, South Africa); Sloan Digital Sky Survey; Observatorio del Roque de los Muchachos of the Instituto de Astrofísica de Canarias (Canary Islands, Spain) and New Technology Telescope (NTT) of La Silla Observatory, Chile.

Mechanisms of spectral and temporal integration in the mustached bat inferior colliculus

PubMed Central

Wenstrup, Jeffrey James; Nataraj, Kiran; Sanchez, Jason Tait

2012-01-01

This review describes mechanisms and circuitry underlying combination-sensitive response properties in the auditory brainstem and midbrain. Combination-sensitive neurons, performing a type of auditory spectro-temporal integration, respond to specific, properly timed combinations of spectral elements in vocal signals and other acoustic stimuli. While these neurons are known to occur in the auditory forebrain of many vertebrate species, the work described here establishes their origin in the auditory brainstem and midbrain. Focusing on the mustached bat, we review several major findings: (1) Combination-sensitive responses involve facilitatory interactions, inhibitory interactions, or both when activated by distinct spectral elements in complex sounds. (2) Combination-sensitive responses are created in distinct stages: inhibition arises mainly in lateral lemniscal nuclei of the auditory brainstem, while facilitation arises in the inferior colliculus (IC) of the midbrain. (3) Spectral integration underlying combination-sensitive responses requires a low-frequency input tuned well below a neuron's characteristic frequency (ChF). Low-ChF neurons in the auditory brainstem project to high-ChF regions in brainstem or IC to create combination sensitivity. (4) At their sites of origin, both facilitatory and inhibitory combination-sensitive interactions depend on glycinergic inputs and are eliminated by glycine receptor blockade. Surprisingly, facilitatory interactions in IC depend almost exclusively on glycinergic inputs and are largely independent of glutamatergic and GABAergic inputs. (5) The medial nucleus of the trapezoid body (MNTB), the lateral lemniscal nuclei, and the IC play critical roles in creating combination-sensitive responses. We propose that these mechanisms, based on work in the mustached bat, apply to a broad range of mammals and other vertebrates that depend on temporally sensitive integration of information across the audible spectrum. PMID:23109917

Discovery of 4-Methyl-N-(4-((4-methylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl)-3-((1-nicotinoylpiperidin-4-yl)oxy)benzamide (CHMFL-ABL/KIT-155) as a Novel Highly Potent Type II ABL/KIT Dual Kinase Inhibitor with a Distinct Hinge Binding.

PubMed

Wang, Qiang; Liu, Feiyang; Wang, Beilei; Zou, Fengming; Qi, Ziping; Chen, Cheng; Yu, Kailin; Hu, Chen; Qi, Shuang; Wang, Wenchao; Hu, Zhenquan; Liu, Juan; Wang, Wei; Wang, Li; Liang, Qianmao; Zhang, Shanchun; Ren, Tao; Liu, Qingsong; Liu, Jing

2017-01-12

The discovery of a novel potent type II ABL/c-KIT dual kinase inhibitor compound 34 (CHMFL-ABL/KIT-155), which utilized a hydrogen bond formed by NH on the kinase backbone and carbonyl oxygen of 34 as a unique hinge binding, is described. 34 potently inhibited purified ABL (IC 50 : 46 nM) and c-KIT kinase (IC 50 : 75 nM) in the biochemical assays and displayed high selectivity (S Score (1) = 0.03) at the concentration of 1 μM among 468 kinases/mutants in KINOMEscan assay. It exhibited strong antiproliferative activities against BCR-ABL/c-KIT driven CML/GISTs cancer cell lines through blockage of the BCR-ABL/c-KIT mediated signaling pathways, arresting cell cycle progression and induction of apoptosis. 34 possessed a good oral PK property and effectively suppressed the tumor progression in the K562 (CML) and GIST-T1 (GISTs) cells mediated xenograft mouse model. The distinct hinge-binding mode of 34 provided a novel pharmacophore for expanding the chemical structure diversity for the type II kinase inhibitors discovery.

Rotational Periods and Starspot Activity of Young Solar-Type Dwarfs in the Open Cluster IC 4665

NASA Technical Reports Server (NTRS)

Allain, S.; Bouvier, J.; Prosser, C.; Marschall, L. A.; Laaksonen, B. D.

1995-01-01

We present the results of a V-band photometric monitoring survey of 15 late-type dwarfs in the young open cluster IC 4665. Low-amplitude periodic light variations are found for 8 stars and ascribed to the modulation by starspots that cover typically a few percent of the stellar disk. Periods range from 0.6 to 3.7 d, translating to equatorial velocities between 13 and 93 km/s. That no period longer than 4 d was detected suggests a relative paucity of extremely slow rotators (V(sub eq) much less than 10 km/s) among late-type dwarfs in IC 4665. The fractional number of slow rotators in IC 4665 is similar to that of Alpha Per cluster, suggesting that IC 4665 is close in age to Alpha Per (approx. 50 Myr).

High-resolution radio study of SNR IC 443 at low radio frequencies

NASA Astrophysics Data System (ADS)

Castelletti, G.; Dubner, G.; Clarke, T.; Kassim, N. E.

2011-10-01

Aims: We investigate the morphology at low radio frequencies of the supernova remnant (SNR) IC 443 in detail and accurately establish its radio continuum spectral properties. Methods: We used the VLA in multiple configurations to produce high-resolution radio images of IC 443 at 74 and 330 MHz. From these data we produced the first sensitive, spatially resolved spectral analysis of the radio emission at long wavelengths. The changes with position in the radio spectral index were correlated with data in near infrared (NIR) from 2MASS, in gamma-rays from VERITAS, and with the molecular 12CO (J = 1 - 0) line emission. Results: The new image at 74 MHz has HPBW = 35'' and rms = 30 mJy beam-1 and at 330 MHz HPBW = 17'' and rms = 1.7 mJy beam-1. The integrated flux densities for the whole SNR are S74 MHzSNR=470±51 Jy and S330 MHzSNR=248±15 Jy. Improved estimates of the integrated spectrum were derived taking a turnover into account to fit the lowest frequency measurements in the literature. Combining our measurements with existing data, we derive an integrated spectral index α10 MHz10700 MHz=-0.39±0.01 with a free-free continuum optical depth at 330 MHz τ330 ~ 7 × 10-4 (τ10 = 1.07); all measurements above ~ 10 MHz are equally consistent with a power law spectrum. For the pulsar wind nebula associated with the compact source CXOU J061705.3+222127, we calculated S330 MHzPWN=0.23±0.05 Jy, S1420 MHzPWN=0.20±0.04 Jy, and α330 MHz8460 MHz˜ 0.0. Substantial variations are observed in spectral index between 74 and 330 MHz across IC 443. The flattest spectral components ( - 0.25 ≤ α ≤ - 0.05) coincide with the brightest parts of the SNR along the eastern border, with an impressive agreement with ionic lines as observed in the 2MASS J and H bands. The diffuse interior of IC 443 has a spectrum steeper than found anywhere in the SNR ( - 0.85 ≤ α ≤ - 0.6), while the southern ridge again has a flatter spectrum (α ~ -0.4). With the available statistics the VERITAS γ-ray emission strikingly matches the CO distribution, but no clear evidence is found for a morphological correlation between the TeV distribution and radio emission. Conclusions: The excellent correspondence between the eastern radio flattest spectrum region and NIR ionic lines strongly suggests that the passage of a fast, dissociating J-type shock across the interacting molecular cloud dissociated the molecules and ionized the gas. We therefore conclude that thermal absorption at 74 MHz (τ74 up to ~0.3) is responsible for the localized spectral index flattening observed along the eastern border of IC 443. Towards the interior of IC 443, the spectrum is consistent with those expected from linear diffusive shock acceleration, while the flatter spectrum in the southern ridge is a consequence of the strong shock/molecular cloud interaction.

Synthesis, molecular structure, spectral analysis, and biological activity of new malonamide derivatives as α-glucosidase inhibitors

NASA Astrophysics Data System (ADS)

Barakat, Assem; Islam, Mohammad Shahidul; Al-Majid, Abdullah Mohammed; Soliman, Saied M.; Ghabbour, Hazem A.; Yousuf, Sammer; Choudhary, M. Iqbal; Ul-Haq, Zaheer

2017-04-01

Two new malonamide derivatives were synthesized via the Michael addition of N1,N3-di(pyridin-2-yl)malonamide to α,β-unsaturated ketones using a 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) catalyst at room temperature. All reactions efficiently furnished the desired malonamide derivatives, which differed only in their substitution on one phenyl group, with one derivative bearing a bromine substituent and the other bearing a methyl group. The structures of newly synthesized compounds were then elucidated by single-crystal X-ray diffraction, infrared spectroscopy, NMR spectroscopy, mass spectrometry, and elemental analysis. In addition, the synthesized compounds were evaluated for their in vitro cytotoxicity against cancer cell lines and for α-glucosidase inhibition. The target compounds exhibited enhanced α-glucosidase inhibition activity (i.e., IC50 = 12.8 ± 0.1 and 28.4 ± 0.2 μM) compared to the common drug acarbose (IC50 = 840 ± 1.73 μM). Both compounds were found to be non-cytotoxic against H460 (lung carcinoma) and T3T (normal fibroblast) cell lines. In addition, the bromo-substituted derivative exhibited weak cytotoxic against cervical cancer HeLa (IC50 = 13.8 ± 0.4 μM) and breast cancer MCF-7 (IC50 = 21.11 ± 0.88 μM) cell lines, while the methyl-substituted derivative showed weak cytotoxicity against the MCF-7 cell line (IC50 = 47.9 ± 0.7 μM). Density functional theory (DFT) B3LYP/6-311G(d,p) calculations were employed to examine the molecular structures and electronic properties of the prepared compounds. As expected, the bromo-derivative (2.2377 D) exhibited a higher polarity than the methyl-derivative (1.9160 D). Furthermore, the HOMO and LUMO diagrams were constructed and the electronic spectra of both compounds were assigned using time-dependent (TD)-DFT calculations. Finally, the calculated NMR chemical shifts correlated well with the experimental data.

Cytotoxicity of fucosterol containing fraction of marine algae against breast and colon carcinoma cell line

PubMed Central

Khanavi, Mahnaz; Gheidarloo, Razieh; Sadati, Nargess; Ardekani, Mohammad Reza Shams; Nabavi, Seyed Mohammad Bagher; Tavajohi, Shohreh; Ostad, Seyed Nasser

2012-01-01

Context: Marine algae produce different secondary metabolites with a wide range of biological activities. Many studies have been achieved on the screening of biological effects of marine organisms and a lot of active compounds were isolated and characterized. Aims: In an attempt to find cytotoxic compound of hexane fraction, isolation, identification, and cytotoxicity of active compound of this fraction were performed. Materials and Methods: In this study, total methanolic (70%) extract and partition fractions of hexane, chloroform (CHCl3), ethyl acetate (EtOAc), and MeOH–H2O of Sargassum angustifolium, Chondria dasyphylla, and Ulva flexuosa, collected from coastlines of the Persian Gulf in south of Iran, were studied against colon carcinoma (HT-29), colorectal adenocarcinoma (Caco-2), breast ductal carcinoma (T47D), and Swiss mouse embryo fibroblast (NIH 3T3) cell lines by MTT assay. Statistical Analysis Used: IC50 (median growth inhibitory concentration) values were calculated by Sigmaplot (10) software. Results: Hexane fraction of Chondria dasyphylla (IC50 82.26 ± 4.09 μg/ml) and MeOH-H2O fraction of Ulva flexuosa (IC50 116.92 ± 8.58 μg/ml) showed cytotoxic activity against proliferation of T47D cells. Hexane fraction of Sargassum angustifolium was also observed for cytotoxicity against T47D and HT-29 cell lines (IC50 166.42 ± 26.7 and 190.24 ± 52.8 μg/ml), respectively. An investigation of a component from the hexane fraction of Sargassum angustifolium yielded a steroidal metabolite, fucosterol, with cytotoxicity in T47D and HT29 (IC50 27.94 ± 9.3 and 70.41 ± 7.5 μg/ml). Conclusions: These results indicated that fucosterol, the most abundant phytosterol in brown algae, is responsible for cytotoxic effect of this extract against breast and colon carcinoma cell lines. PMID:22438665

Development of a walleye spleen stromal cell line sensitive to viral hemorrhagic septicemia virus (VHSV IVb) and to protection by synthetic dsRNA.

PubMed

Vo, Nguyen T K; Bender, Aaron W; Ammendolia, Dustin A; Lumsden, John S; Dixon, Brian; Bols, Niels C

2015-07-01

A cell line, WE-spleen6, has been developed from the stromal layer of primary spleen cell cultures. On conventional plastic, WE-spleen6 cells had a spindle-shaped morphology at low cell density but grew to become epithelial-like at confluency. On the commercial extracellular matrix (ECM), Matrigel, the cells remained spindle-shaped and formed lumen-like structures. WE-spleen6 cells had intermediate filament protein, vimentin and the ECM protein, collagen I, but not smooth muscle α-actin (SMA) and von Willebrand factor (vWF) and lacked alkaline phosphatase and phagocytic activities. WE-spleen6 was more susceptible to infection with VHSV IVb than a fibroblast and epithelial cell lines from the walleye caudal fin, WE-cfin11f and WE-cfin11e, respectively. Viral transcripts and proteins appeared earlier in WE-spleen6 cultures as did cytopathic effect (CPE) and significant virus production. The synthetic double-stranded RNA (dsRNA), polyinosinic: polycytidylic acid (pIC), induced the antiviral protein Mx in both cell lines. Treating WE-spleen6 cultures with pIC prior to infection with VHSV IVb inhibited the early accumulation of viral transcripts and proteins and delayed the appearance of CPE and significant viral production. Of particular note, pIC caused the disappearance of viral P protein 2 days post infection. WE-spleen6 should be useful for investigating the impact of VHSV IVb on hematopoietic organs and the actions of pIC on the rhabdovirus life cycle. Copyright © 2015 Elsevier Ltd. All rights reserved.

Induction of antiviral genes, Mx and vig-1, by dsRNA and Chum salmon reovirus in rainbow trout monocyte/macrophage and fibroblast cell lines.

PubMed

DeWitte-Orr, Stephanie J; Leong, Jo-Ann C; Bols, Niels C

2007-09-01

The expression of potential antiviral genes, Mx1, Mx2, Mx3 and vig-1, was studied in two rainbow trout cell lines: monocyte/macrophage RTS11 and fibroblast-like RTG-2. Transcripts were monitored by RT-PCR; Mx protein by Western blotting. In unstimulated cultures Mx1 and vig-1 transcripts were seen occasionally in RTS11 but rarely in RTG-2. A low level of Mx protein was seen in unstimulated RTS11 but not in RTG-2. In both cell lines, Mx and vig-1 transcripts were induced by a dsRNA, poly inosinic: poly cytidylic acid (poly IC), and by Chum salmon reovirus (CSV). Medium conditioned by cells previously exposed to poly IC or CSV and assumed to contain interferon (IFN) induced the antiviral genes in RTS11. However, RTG-2 responded only to medium conditioned by RTG-2 exposed previously to CSV. In both cell lines, poly IC and CSV induced Mx transcripts in the presence of cycloheximide, suggesting a direct induction mechanism, independent of IFN, was also possible. For CSV, ribavirin blocked induction in RTS11 but not in RTG-2, suggesting viral RNA synthesis was required for induction only in RTS11. In both RTS11 and RTG-2 cultures, Mx protein showed enhanced accumulation by 24h after exposure to poly IC and CSV, but subsequently Mx protein levels declined back to control levels in RTS11 but not in RTG-2. These results suggest that Mx can be regulated differently in macrophages and fibroblasts.

Determination of the appropriate catheter length and place for needle thoracostomy by using computed tomography scans of pneumothorax patients.

PubMed

Akoglu, Haldun; Akoglu, Ebru Unal; Evman, Serdar; Akoglu, Tayfun; Altinok, Arzu Denizbasi; Guneysel, Ozlem; Onur, Ozge Ecmel; Eroglu, Serkan Emre

2013-09-01

The primary goal of this study was to compare the chest wall thicknesses (CWT) at the 2nd intercostal space (ICS) at the mid-clavicular line (MCL) and 5th ICS at the mid-axillary line (MAL) in a population of patients with a CT confirmed pneumothorax (PTX). This result will help physicians to determine the optimum needle thoracostomy (NT) puncture site in patients with a PTX. All trauma patients who presented consecutively to A&E over a 12-month period were included. Among all the trauma patients with a chest CT (4204 patients), 160 were included in the final analysis. CWTs were measured at both sides and were compared in all subgroup of patients. The average CWT for men on the 2nd ICS-MCL was 38mm and for women was 52mm; on the other hand, on the 5th ICS-MAL was 33mm for men and 38mm for women. On the 2nd ICS-MCL 17% of men and 48% of women; on the 5th ICS-MAL 13% of men and 33% of women would be inaccessible with a routine 5-cm catheter. Patients with trauma, subcutaneous emphysema and multiple rib fractures would have thicker CWT on the 2nd ICS-MCL. Patients with trauma, lung contusion, sternum fracture, subcutaneous emphysema and multiple rib fractures would have thicker CWT on the 5th ICS-MAL. This study confirms that a 5.0-cm catheter would be unlikely to access the pleural space in at least 1/3 of female and 1/10 of male Turkish trauma patients, regardless of the puncture site. If NT is needed, the 5th ICS-MAL is a better option for a puncture site with thinner CWT. Copyright © 2012 Elsevier Ltd. All rights reserved.

Cytotoxic and Antimicrobial Activity of Dehydrozingerone based Cyclopropyl Derivatives.

PubMed

Burmudžija, Adrijana Z; Muškinja, Jovana M; Kosanić, Marijana M; Ranković, Branislav R; Novaković, Slađana B; Đorđević, Snežana B; Stanojković, Tatjana P; Baskić, Dejan D; Ratković, Zoran R

2017-08-01

A small series of 1-acetyl-2-(4-alkoxy-3-methoxyphenyl)cyclopropanes was prepared, starting from dehydrozingerone (4-(4-hydroxy-3-methoxyphenyl)-3-buten-2-one) and its O-alkyl derivatives. Their microbiological activities toward some strains of bacteria and fungi were tested, as well as their in vitro cytotoxic activity against some cancer cell lines (HeLa, LS174 and A549). All synthesized compounds showed significant antimicrobial activity and expressed cytotoxic activity against tested carcinoma cell lines, but they showed no significant influence on normal cell line (MRC5). Butyl derivative is the most active on HeLa cells (IC 50 = 8.63 μm), while benzyl one is active against LS174 and A549 cell lines (IC 50 = 10.17 and 12.15 μm, respectively). © 2017 Wiley-VHCA AG, Zurich, Switzerland.

An analog integrated circuit beamformer for high-frequency medical ultrasound imaging.

PubMed

Gurun, Gokce; Zahorian, Jaime S; Sisman, Alper; Karaman, Mustafa; Hasler, Paul E; Degertekin, F Levent

2012-10-01

We designed and fabricated a dynamic receive beamformer integrated circuit (IC) in 0.35-μm CMOS technology. This beamformer IC is suitable for integration with an annular array transducer for high-frequency (30-50 MHz) intravascular ultrasound (IVUS) imaging. The beamformer IC consists of receive preamplifiers, an analog dynamic delay-and-sum beamformer, and buffers for 8 receive channels. To form an analog dynamic delay line we designed an analog delay cell based on the current-mode first-order all-pass filter topology, as the basic building block. To increase the bandwidth of the delay cell, we explored an enhancement technique on the current mirrors. This technique improved the overall bandwidth of the delay line by a factor of 6. Each delay cell consumes 2.1-mW of power and is capable of generating a tunable time delay between 1.75 ns to 2.5 ns. We successfully integrated the fabricated beamformer IC with an 8-element annular array. Experimental test results demonstrated the desired buffering, preamplification and delaying capabilities of the beamformer.

Chemical composition and in vitro antitrypanosomal activity of fractions of essential oil from Cymbopogon nardus L.

PubMed

Muhd Haffiz, J; Norhayati, I; Getha, K; Nor Azah, M A; Mohd Ilham, A; Lili Sahira, H; Roshan Jahn, M S; Muhd Syamil, A

2013-03-01

Essential oil from Cymbopogon nardus was evaluated for activity against Trypanosoma brucei brucei BS221 (IC50 = 0.31 ± 0.03 μg/mL) and cytotoxic effect on normal kidney (Vero) cells (IC50 = >100 μg/mL). The crude essential oil was subjected to various chromatography techniques afforded active sub fractions with antitrypanosomal activity; F4 (IC50 = 0.61 ± 0.06 μg/mL), F6 (IC50= 0.73 ± 0.33 μg/mL), F7 (IC50 = 1.15 ± 0 μg/mL) and F8 (IC50 = 1.11 ± 0.01 μg/mL). These active fractions did not exhibit any toxic effects against Vero cell lines and the chemical profiles investigation indicated presence of α-and γ-eudesmol, elemol, α-cadinol and eugenol by GC/MS analysis.

Mechanisms of activation of the paternally expressed genes by the Prader-Willi imprinting center in the Prader-Willi/Angelman syndromes domains

PubMed Central

Rabinovitz, Shiri; Kaufman, Yotam; Ludwig, Guy; Razin, Aharon; Shemer, Ruth

2012-01-01

The Prader-Willi syndrome/Angelman syndrome (PWS/AS) imprinted domain is regulated by a bipartite imprinting control center (IC) composed of a sequence around the SNRPN promoter (PWS-IC) and a 880-bp sequence located 35 kb upstream (AS-IC). The AS-IC imprint is established during gametogenesis and confers repression upon PWS-IC on the maternal allele. Mutation at PWS-IC on the paternal allele leads to gene silencing across the entire PWS/AS domain. This silencing implies that PWS-IC functions on the paternal allele as a bidirectional activator. Here we examine the mechanism by which PWS-IC activates the paternally expressed genes (PEGs) using transgenes that include the PWS-IC sequence in the presence or absence of AS-IC and NDN, an upstream PEG, as an experimental model. We demonstrate that PWS-IC is in fact an activator of NDN. This activation requires an unmethylated PWS-IC in the gametes and during early embryogenesis. PWS-IC is dispensable later in development. Interestingly, a similar activation of a nonimprinted gene (APOA1) was observed, implying that PWS-IC is a universal activator. To decipher the mechanism by which PWS-IC confers activation of remote genes, we performed methylated DNA immunoprecipitation (MeDIP) array analysis on lymphoblast cell lines that revealed dispersed, rather than continued differential methylation. However, chromatin conformation capture (3c) experiments revealed a physical interaction between PWS-IC and the PEGs, suggesting that activation of PEGs may require their proximity to PWS-IC. PMID:22529396

Classification of PSN J12015272-1852183 as a young type Ic SN

NASA Astrophysics Data System (ADS)

Harutyunyan, A.; Benetti, S.; Pastorello, A.; Cappellaro, E.; Tomasella, L.; Ochner, P.; Turatto, M.

2013-06-01

We report the spectroscopic classification (range 335-785 nm; resolution 1.5 nm) of PSN J12015272-1852183 discovered by the CHASE project on June 22.12 UT. The spectrogram obtained on June 23.88 UT with the TNG Telescope (+Dolores), shows that this is a type-Ic supernova. A good match is found with the type-Ic supernova 1994I (Millard et al 1999, ApJ 527, 746) at about six days before maximum light.

Extended Narrow-Line Region in Seyfert Galaxies

NASA Astrophysics Data System (ADS)

Congiu, Enrico; Contini, Marcella.; Ciroi, Stefano; Cracco, Valentina; Di Mille, Francesco; Berton, Marco; Frezzato, Michele; La Mura, Giovanni; Rafanelli, Piero

2017-10-01

We present our recent results about the extended narrow-line region (ENLR) of two nearby Seyfert 2 galaxies (IC 5063 and NGC 7212) obtained by modelling the observed line profiles and spectra with composite models (photoionization+shocks) in the different regions surrounding the AGN. Then, we compare the Seyfert 2 ENLRs with the very extended one recently discovered in the narrow-line Seyfert 1 (NLS1) galaxy Mrk 783. We have found several evidences of interaction between the ISM of the galaxies and their radio jets, such as a) the contribution of shocks in ionizing the high velocity gas, b) the complex kinematics showed by the profile of the emission lines, c) the high fragmentation of matter, etc. The results suggest that the ENLR of IC 5063 have a hollow bi-conical shape, with one edge aligned to the galaxy disk, which may cause some kind of dependence on velocity of the ionization parameter. Regarding the Mrk 783 properties, it is found that the extension of the optical emission is almost twice the size of the radio one and it seems due to the AGN activity, although there is contamination by star formation around 12 arcsec from the nucleus. Diagnostic diagrams excluded the contribution of star formation in IC 5063 and NGC 7212, while the shock contribution was used to explain the spectra emitted by their high velocity gas.

Synthesis and anti-tumor evaluation of panaxadiol halogen-derivatives.

PubMed

Xiao, Shengnan; Chen, Shuai; Sun, Yuanyuan; Zhou, Wuxi; Piao, Huri; Zhao, Yuqing

2017-09-01

In the current work, 13 novel panaxadiol (PD) derivatives were synthesized by reacting with chloroacetyl chloride and bromoacetyl bromide. Their in vitro antitumor activities were evaluated on three human tumor cell lines (HCT-116, BGC-823, SW-480) and three normal cells (human gastric epithelial cell line-GES-1, hair follicle dermal papilla cell line-HHDPC and rat myocardial cell line-H9C2) by MTT assay. Compared with PD, the results demonstrated that compound 1e, 2d, 2e showed significant anti-tumor activity against three tumor cell lines, the IC50 value of compound 2d against HCT-116 was the lowest (3.836μM). The anti-tumor activity of open-ring compounds are significantly better than the compounds of C-25 cyclization. Compound 1f, 2f, 2g showed the strong anti-tumor activity. The IC50 value of compound 2g against BGC-823 and SW-480 were the lowest (0.6μM and 0.1μM, respectively). Combined with cytotoxicity test, the IC50 value of compound 1e, 2d, 2e are greater than 100. the open-ring compounds (1f, 2f, 2g) showed a strong toxicity. The toxicity of 1f is lower than 2f and 2g. These compounds may be useful for the development of novel antiproliferative agents. Copyright © 2017. Published by Elsevier Ltd.

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

Knauth, D. C.; Taylor, C. J.; Federman, S. R.

Measurements of the lithium isotopic ratio in the diffuse interstellar medium from high-resolution spectra of the Li i λ 6708 resonance doublet have now been reported for a number of lines of sight. The majority of the results for the {sup 7}Li/{sup 6}Li ratio are similar to the solar system ratio of 12.2, but the line of sight toward o Per, a star near the star-forming region IC 348, gave a ratio of about two, the expected value for gas exposed to spallation and fusion reactions driven by cosmic rays. To examine the association of IC 348 with cosmic raysmore » more closely, we measured the lithium isotopic ratio for lines of sight to three stars within a few parsecs of o Per. One star, HD 281159, has {sup 7}Li/{sup 6}Li ≃ 2 confirming production by cosmic rays. The lithium isotopic ratio toward o Per and HD 281159 together with published analyses of the chemistry of interstellar diatomic molecules suggest that the superbubble surrounding IC 348 is the source of the cosmic rays.« less

Chemistry of Renieramycins. 17. A New Generation of Renieramycins: Hydroquinone 5-O-Monoester Analogues of Renieramycin M as Potential Cytotoxic Agents against Non-Small-Cell Lung Cancer Cells.

PubMed

Chamni, Supakarn; Sirimangkalakitti, Natchanun; Chanvorachote, Pithi; Saito, Naoki; Suwanborirux, Khanit

2017-05-26

A series of hydroquinone 5-O-monoester analogues of renieramycin M were semisynthesized via bishydroquinonerenieramycin M (5) prepared from renieramycin M (1), a major cytotoxic bistetrahydroisoquinolinequinone alkaloid isolated from the Thai blue sponge Xestospongia sp. All 20 hydroquinone 5-O-monoester analogues possessed cytotoxicity with IC 50 values in nanomolar concentrations against the H292 and H460 human non-small-cell lung cancer (NSCLC) cell lines. The improved cytotoxicity toward the NSCLC cell lines was observed from the 5-O-monoester analogues such as 5-O-acetyl ester 6a and 5-O-propanoyl ester 7e, which exhibited 8- and 10-fold increased cytotoxicity toward the H292 NSCLC cell line (IC 50 3.0 and 2.3 nM, respectively), relative to 1 (IC 50 24 nM). Thus, the hydroquinone 5-O-monoester analogues are a new generation of the renieramycins to be further developed as potential marine-derived drug candidates for lung cancer treatment.

Anticancer potential and mechanism of action of mango ginger (Curcuma amada Roxb.) supercritical CO₂ extract in human glioblastoma cells.

PubMed

Ramachandran, Cheppail; Lollett, Ivonne V; Escalon, Enrique; Quirin, Karl-Werner; Melnick, Steven J

2015-04-01

Mango ginger (Curcuma amada Roxb.) is among the less-investigated species of Curcuma for anticancer properties. We have investigated the anticancer potential and the mechanism of action of a supercritical CO2 extract of mango ginger (CA) in the U-87MG human glioblastoma cell line. CA demonstrated higher cytotoxicity than temozolomide, etoposide, curcumin, and turmeric force with IC50, IC75, and IC90 values of 4.92 μg/mL, 12.87 μg/mL, and 21.30 μg/mL, respectively. Inhibitory concentration values of CA for normal embryonic mouse hypothalamus cell line (mHypoE-N1) is significantly higher than glioblastoma cell line, indicating the specificity of CA against brain tumor cells. CompuSyn analysis indicates that CA acts synergistically with temozolomide and etoposide for the cytotoxicity with combination index values of <1. CA treatment also induces apoptosis in glioblastoma cells in a dose-dependent manner and downregulates genes associated with apoptosis, cell proliferation, telomerase activity, oncogenesis, and drug resistance in glioblastoma cells. © The Author(s) 2014.

Parsec-scale Variations in the 7Li I/6Li I Isotope Ratio Toward IC 348 and the Perseus OB 2 Association

NASA Astrophysics Data System (ADS)

Knauth, D. C.; Taylor, C. J.; Ritchey, A. M.; Federman, S. R.; Lambert, D. L.

2017-01-01

Measurements of the lithium isotopic ratio in the diffuse interstellar medium from high-resolution spectra of the Li I λ6708 resonance doublet have now been reported for a number of lines of sight. The majority of the results for the 7Li/6Li ratio are similar to the solar system ratio of 12.2, but the line of sight toward o Per, a star near the star-forming region IC 348, gave a ratio of about two, the expected value for gas exposed to spallation and fusion reactions driven by cosmic rays. To examine the association of IC 348 with cosmic rays more closely, we measured the lithium isotopic ratio for lines of sight to three stars within a few parsecs of o Per. One star, HD 281159, has 7Li/6Li ≃ 2 confirming production by cosmic rays. The lithium isotopic ratio toward o Per and HD 281159 together with published analyses of the chemistry of interstellar diatomic molecules suggest that the superbubble surrounding IC 348 is the source of the cosmic rays. Based on observations obtained with the Hobby-Eberly Telescope, which is a joint project of the University of Texas at Austin, the Pennsylvania State University, Ludwig-Maximilians-Universität München, and Georg-August-Universität Göttingen.

Tomato ( Lycopersicon esculentum ) seeds: new flavonols and cytotoxic effect.

PubMed

Ferreres, Federico; Taveira, Marcos; Pereira, David M; Valentão, Patrícia; Andrade, Paula B

2010-03-10

In this study, seeds of Lycopersicon esculentum Mill. were analyzed by HPLC/UV-PAD/MS(n)-ESI. Fourteen flavonoids were identified, including quercetin, kaempferol, and isorhamnetin derivatives, with 13 of them being reported for the first time in tomato seeds. The major identified compounds were quercetin-3-O-sophoroside, kaempferol-3-O-sophoroside, and isorhamnetin-3-O-sophoroside. A significant cell proliferation inhibition (>80%), against rat basophile leukemia (RBL-2H3) cell line, was observed with this extract (IC(50) = 5980 microg/mL). For acetylcholinesterase inhibitory activity, a concentration-dependent effect was verified (IC(20) = 2400 microg/mL). The same behavior was noted regarding antioxidant capacity, evaluated against DPPH (IC(10) = 284 microg/mL), nitric oxide (IC(25) = 396 microg/L), and superoxide radicals (IC(25) = 3 microg/mL).

Isoindolinone inhibitors of the murine double minute 2 (MDM2)-p53 protein-protein interaction: structure-activity studies leading to improved potency.

PubMed

Hardcastle, Ian R; Liu, Junfeng; Valeur, Eric; Watson, Anna; Ahmed, Shafiq U; Blackburn, Timothy J; Bennaceur, Karim; Clegg, William; Drummond, Catherine; Endicott, Jane A; Golding, Bernard T; Griffin, Roger J; Gruber, Jan; Haggerty, Karen; Harrington, Ross W; Hutton, Claire; Kemp, Stuart; Lu, Xiaohong; McDonnell, James M; Newell, David R; Noble, Martin E M; Payne, Sara L; Revill, Charlotte H; Riedinger, Christiane; Xu, Qing; Lunec, John

2011-03-10

Inhibition of the MDM2-p53 interaction has been shown to produce an antitumor effect, especially in MDM2 amplified tumors. The isoindolinone scaffold has proved to be versatile for the discovery of MDM2-p53 antagonists. Optimization of previously reported inhibitors, for example, NU8231 (7) and NU8165 (49), was guided by MDM2 NMR titrations, which indicated key areas of the binding interaction to be explored. Variation of the 2-N-benzyl and 3-alkoxy substituents resulted in the identification of 3-(4-chlorophenyl)-3-((1-(hydroxymethyl)cyclopropyl)methoxy)-2-(4-nitrobenzyl)isoindolin-1-one (74) as a potent MDM2-p53 inhibitor (IC(50) = 0.23 ± 0.01 μM). Resolution of the enantiomers of 74 showed that potent MDM2-p53 activity primarily resided with the (+)-R-enantiomer (74a; IC(50) = 0.17 ± 0.02 μM). The cellular activity of key compounds has been examined in cell lines with defined p53 and MDM2 status. Compound 74a activates p53, MDM2, and p21 transcription in MDM2 amplified cells and shows moderate selectivity for wild-type p53 cell lines in growth inhibition assays.

Cytotoxic Effects of Sarcophyton sp. Soft Corals—Is There a Correlation to Their NMR Fingerprints?

PubMed Central

Farag, Mohamed A.; Fekry, Mostafa I.; Al-Hammady, Montasser A.; Khalil, Mohamed N.; El-Seedi, Hesham R.; Meyer, Achim; Westphal, Hildegard; Wessjohann, Ludger A.

2017-01-01

Sarcophyton sp. soft corals are rich in cembranoid diterpenes, which represent the main chemical defense of corals against their natural predators in addition to their myriad biological effects in humans. Quantitative NMR (qNMR) was applied for assessing the diterpene variation in 16 soft coral specimens in the context of their genotype, origin, and growing habitat. qNMR revealed high diterpene levels in Sarcophyton sp. compared to Sinularia and Lobophyton, with (ent)sarcophines as major components (17–100 µg/mg) of the coral tissues. Multivariate data analysis was employed to classify samples based on the quantified level of diterpenes, and compared to the untargeted NMR approach. Results revealed that qNMR provided a stronger classification model of Sarcophyton sp. than untargeted NMR fingerprinting. Additionally, cytotoxicity of soft coral crude extracts was assessed against androgen-dependent prostate cancer cell lines (PC3) and androgen-independent colon cancer cell lines (HT-29), with IC50 values ranging from 10–60 µg/mL. No obvious correlation between the extracts’ IC50 values and their diterpene levels was found using either Spearman or Pearson correlations. This suggests that this type of bioactivity may not be easily predicted by NMR metabolomics in soft corals, or is not strongly correlated to measured diterpene levels. PMID:28677625

Cytotoxic Effects of Sarcophyton sp. Soft Corals-Is There a Correlation to Their NMR Fingerprints?

PubMed

Farag, Mohamed A; Fekry, Mostafa I; Al-Hammady, Montasser A; Khalil, Mohamed N; El-Seedi, Hesham R; Meyer, Achim; Porzel, Andrea; Westphal, Hildegard; Wessjohann, Ludger A

2017-07-04

Sarcophyton sp. soft corals are rich in cembranoid diterpenes, which represent the main chemical defense of corals against their natural predators in addition to their myriad biological effects in humans. Quantitative NMR (qNMR) was applied for assessing the diterpene variation in 16 soft coral specimens in the context of their genotype, origin, and growing habitat. qNMR revealed high diterpene levels in Sarcophyton sp. compared to Sinularia and Lobophyton , with (ent)sarcophines as major components (17-100 µg/mg) of the coral tissues. Multivariate data analysis was employed to classify samples based on the quantified level of diterpenes, and compared to the untargeted NMR approach. Results revealed that qNMR provided a stronger classification model of Sarcophyton sp. than untargeted NMR fingerprinting. Additionally, cytotoxicity of soft coral crude extracts was assessed against androgen-dependent prostate cancer cell lines (PC3) and androgen-independent colon cancer cell lines (HT-29), with IC 50 values ranging from 10-60 µg/mL. No obvious correlation between the extracts' IC 50 values and their diterpene levels was found using either Spearman or Pearson correlations. This suggests that this type of bioactivity may not be easily predicted by NMR metabolomics in soft corals, or is not strongly correlated to measured diterpene levels.

Accretion Rate: An Axis Of Agn Unification

NASA Astrophysics Data System (ADS)

Trump, Jonathan R.; Impey, C. D.; Kelly, B. C.

2011-01-01

We show how accretion rate governs the physical properties of broad-line, narrow-line, and lineless active galactic nuclei (AGNs). We avoid the systematic errors plaguing previous studies of AGN accretion rate by using accurate accretion luminosities from well-sampled multiwavelength SEDs from the Cosmic Evolution Survey (COSMOS), and accurate black hole masses derived from virial scaling relations (for broad-line AGNs) or host-AGN relations (for narrow-line and lineless AGNs). In general, broad emission lines are present only at the highest accretion rates (L/L_Edd>0.01), and these rapidly accreting AGNs are observed as broad-line AGNs or possibly as obscured narrow-line AGNs. Narrow-line and lineless AGNs at lower specific accretion rates (L/L_Edd<0.01) are unobscured and yet lack a broad line region. The disappearance of the broad emission lines is caused by an expanding radiatively inefficient accretion flow (RIAF) at the inner radius of the accretion disk. The presence of the RIAF also drives L/L_Edd<0.01 narrow-line and lineless AGNs to be 10-100 times more radio-luminous than broad-line AGNs, since the unbound nature of the RIAF means it is easier to form a radio outflow. The IR torus signature also tends to become weaker or disappear from L/L_Edd<0.01 AGNs, although there may be additional mid-IR synchrotron emission associated with the RIAF. Together these results suggest that specific accretion rate is an important physical "axis" of AGN unification, described by a simple model.

Broad-band emission properties of central engine powered supernova ejecta interacting with a circumstellar medium

NASA Astrophysics Data System (ADS)

Suzuki, Akihiro; Maeda, Keiichi

2018-04-01

We investigate broad-band emission from supernova ejecta powered by a relativistic wind from a central compact object. A recent two-dimensional hydrodynamic simulation studying the dynamical evolution of supernova ejecta with a central energy source has revealed that outermost layers of the ejecta are accelerated to mildly relativistic velocities because of the breakout of a hot bubble driven by the energy injection. The outermost layers decelerate as they sweep a circumstellar medium surrounding the ejecta, leading to the formation of the forward and reverse shocks propagating in the circumstellar medium and the ejecta. While the ejecta continue to release the internal energy as thermal emission from the photosphere, the energy dissipation at the forward and reverse shock fronts gives rise to non-thermal emission. We calculate light curves and spectral energy distributions of thermal and non-thermal emission from central engine powered supernova ejecta embedded in a steady stellar wind with typical mass loss rates for massive stars. The light curves are compared with currently available radio and X-ray observations of hydrogen-poor superluminous supernovae, as well as the two well-studied broad-lined Ic supernovae, 1998bw and 2009bb, which exhibit bright radio emission indicating central engine activities. We point out that upper limits on radio luminosities of nearby superluminous supernovae may indicate the injected energy is mainly converted to thermal radiation rather than creating mildly relativistic flows owing to photon diffusion time scales comparable to the injection time scale.

Kinetic properties of Streptomyces canarius L- Glutaminase and its anticancer efficiency.

PubMed

Reda, Fifi M

2015-01-01

L-glutaminase was produced by Streptomyces canarius FR (KC460654) with an apparent molecular mass of 44 kDa. It has 17.9 purification fold with a final specific activity 132.2 U/mg proteins and 28% yield recovery. The purified L-glutaminase showed a maximal activity against L-glutamine when incubated at pH 8.0 at 40 °C for 30 min. It maintained its stability at wide range of pH from 5.0 11.0 and thermal stable up to 60 °C with Tm value 57.5 °C. It has high affinity and catalytic activity for L-glutamine (Km 0.129 mM, Vmax 2.02 U/mg/min), followed by L-asparagine and L-aspartic acid. In vivo, L-glutaminase showed no observed changes in liver; kidney functions; hematological parameters and slight effect on RBCs and level of platelets after 10 days of rabbit's injection. The anticancer activity of L-glutaminase was also tested against five types of human cancer cell lines using MTT assay in vitro. L-glutaminase has a significant efficiency against Hep-G2 cell (IC50, 6.8 μg/mL) and HeLa cells (IC50, 8.3 μg/mL), while the growth of MCF-7 cells was not affected. L-glutaminase has a moderate cytotoxic effect against HCT-116 cell (IC50, 64.7 μg/mL) and RAW 264.7 cell (IC50, 59.3 μg/mL).

OBSERVATIONAL LIMITS ON TYPE 1 ACTIVE GALACTIC NUCLEUS ACCRETION RATE IN COSMOS

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

Trump, Jonathan R.; Impey, Chris D.; Gabor, Jared

2009-07-20

We present black hole masses and accretion rates for 182 Type 1 active galactic nuclei (AGNs) in COSMOS. We estimate masses using the scaling relations for the broad H {beta}, Mg II, and C IV emission lines in the redshift ranges 0.16 < z < 0.88, 1 < z < 2.4, and 2.7 < z < 4.9. We estimate the accretion rate using an Eddington ratio L{sub I}/L{sub Edd} estimated from optical and X-ray data. We find that very few Type 1 AGNs accrete below L{sub I} /L{sub Edd} {approx} 0.01, despite simulations of synthetic spectra which show that themore » survey is sensitive to such Type 1 AGNs. At lower accretion rates the broad-line region may become obscured, diluted, or nonexistent. We find evidence that Type 1 AGNs at higher accretion rates have higher optical luminosities, as more of their emission comes from the cool (optical) accretion disk with respect to shorter wavelengths. We measure a larger range in accretion rate than previous works, suggesting that COSMOS is more efficient at finding low accretion rate Type 1 AGNs. However, the measured range in accretion rate is still comparable to the intrinsic scatter from the scaling relations, suggesting that Type 1 AGNs accrete at a narrow range of Eddington ratio, with L{sub I} /L{sub Edd} {approx} 0.1.« less

Hints of correlation between broad-line and radio variations for 3C 120

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

Liu, H. T.; Bai, J. M.; Li, S. K.

2014-01-01

In this paper, we investigate the correlation between broad-line and radio variations for the broad-line radio galaxy 3C 120. By the z-transformed discrete correlation function method and the model-independent flux randomization/random subset selection (FR/RSS) Monte Carlo method, we find that broad Hβ line variations lead the 15 GHz variations. The FR/RSS method shows that the Hβ line variations lead the radio variations by a factor of τ{sub ob} = 0.34 ± 0.01 yr. This time lag can be used to locate the position of the emitting region of radio outbursts in the jet, on the order of ∼5 lt-yr frommore » the central engine. This distance is much larger than the size of the broad-line region. The large separation of the radio outburst emitting region from the broad-line region will observably influence the gamma-ray emission in 3C 120.« less

Seyfert Galaxies in the Infrared

NASA Astrophysics Data System (ADS)

Ruiz-Nishiky, Milagros

1997-10-01

This thesis contains complementary aspects of the Seyfert phenomenon, each of which is analysed to bring a better understanding of present unification theories. Observations of the nuclear regions of various types of Seyfert galaxies were mostly made at infrared wavelengths which allow the study of dusty environments and provide new information on the physical conditions of these objects. For example, near infrared spectroscopy of Seyfert 2 galaxies revealed that there is a subclass of type 2 Seyferts with hot IR excess at ~3μm with broad IR emission lines suggesting that some Seyfert 2s do in fact contain a hidden Seyfert 1 nucleus. Additional spectropolarimetry showed that the scattering screens, postulated in the standard model, are not always present in Seyfert 2s. At mid infrared wavelengths, it was found that the 10 μm nuclear emission of Seyferts with broad emission lines is intrinsically brighter than that of Seyferts with no broad lines. The extended 10μm emission shows that Seyfert 2 galaxies present enhanced star-formation when compared to Seyfert 1s. Both results pose obstacles for present unification ideas and I discuss possible interpretations to these observations. Seyfert galaxies were also observed at radio wavelengths to study their large scale emission of 1-0 CO. Surprisingly, this emission usually related with star formation activity was found to be similar in both types of Seyfert galaxies and therefore does not explain why Seyfert 2 galaxies have enhanced star formation as concluded in the 10μm study. A study of galaxy morphology and companions in this set of Seyferts shows at a significant statistical level that Seyfert 2s present a higher incidence of asymmetric morphologies compared to Seyfert 1s and field galaxies, and therefore are undergoing gravitational perturbations which may induce star formation. Near infrared spectroscopy of a large sample of Seyfert galaxies is analysed to study the excitation mechanisms of (FeII) and H2 lines in the NLR of Seyfert galaxies, a subject which is in great debate at present. Here I present some results indicating that shock excitation is likely, but not always, the dominant mechanism that excites these IR lines.

32 CFR 260.3 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-07-01

...-controlled property. Cafeteria. A food dispensing facility capable of providing a broad variety of prepared foods and beverages (including hot meals) primarily through the use of a line where the customer serves... facilities are always provided. The DoD Component food dispensing facilities that conduct cafeteria-type...

Cytotoxicity evaluation of a new set of 2-aminobenzo[de]iso-quinoline-1,3-diones.

PubMed

Al-Salahi, Rashad; Alswaidan, Ibrahim; Marzouk, Mohamed

2014-12-04

A new series of 2-amino-benzo[de]isoquinoline-1,3-diones was synthesized and fully characterized in our previous paper. Here, their cytotoxic effects have been evaluated in vitro in relation to colon HCT-116, hepatocellular Hep-G2 and breast MCF-7 cancer cell lines, using a crystal violet viability assay. The IC50-values of the target compounds are reported in µg/mL, using doxorubicin as a reference drug. The findings revealed that compounds 14, 15, 16, 21 and 22 had significant cytotoxic effects against HCT-116, MCF-7 and Hep-G2 cell lines. Their IC50 values ranged between 1.3 and 8.3 μg/mL in relation to doxorubicin (IC50 ≈ 0.45-0.89 μg/mL). Therefore, these compounds could be used as templates for furthering the development and design of more potent antitumor agents through structural modification.

PIG (partially ionized globule) anatomy - Density and temperature structure of the bright-rimmed globule IC 1396E

NASA Technical Reports Server (NTRS)

Serabyn, E.; Guesten, R.; Mundy, L.

1993-01-01

The density and temperature structure of the bright-rimmed cometary globule IC 1396E is estimated, and the possibility that recent internal star formation was triggered by the ionization front in its southern surface is assessed. On the basis of NH3 data, gas temperatures in the globule are found to increase outward from the center, from a minimum of 17 K in its tail to a maximum of 26 K on the surface most directly facing the stars ionizing IC 1396. On the basis of a microturbulent radiative transfer code to model the radial dependence of the CS line intensities, and also the intensities of the optically thin 2-1 and 5-4 lines toward the cloud center, a radial density dependence of r exp -1.55 to r exp -1.75 is found.

Purification and characterization of a novel type i ribosome inactivating protein, pachyerosin, from Pachyrhizus erosus seeds, and preparation of its immunotoxin against human hepatoma cells.

PubMed

Guo, Jin-Lin; Cheng, Yuan-Liu; Qiu, Yi; Shen, Cai-Hong; Yi, Bin; Peng, Cheng

2014-07-01

Pachyrhizus erosus seeds have a high protein content and are used in China due to their cytotoxic effect. Here we report the biological and pharmacological activity of the protein extracts from P. erosus seeds. A novel ribosome-inactivating protein, pachyerosin, from P. erosus seeds was successively purified to homogeneity using ammonium sulfate precipitation, DEAE-sepharose FF, and Sephacryl S-200. Pachyerosin showed to be a type I ribosome-inactivating protein with a molecular mass of 29 kDa and an isoelectric point of 9.19. It strongly inhibited protein synthesis of rabbit reticulocyte lysate with an IC50 of 0.37 ng/mL and showed N-glycosidase activity on rat liver ribosomes with an EC50 of 85.9 pM. The N-terminal 27 amino acids of pachyerosin revealed a 60.71% sequence identity with abrin A from the seeds of Abrus precatorius. With the aim of targeting the delivery of pachyerosin, immunotoxin was prepared by conjugating pachyerosin with anti-human AFP monoclonal antibodies SM0736. The immunotoxin pachyerosin-SM0736 efficiently inhibited the growth of the human hepatoma cell line HuH-7 with an IC50 of 0.050 ± 0.004 nM, 2360 times lower than that of pachyerosin and 430 times lower than that of the immunotoxin against human gastric cancer cell line SGC7901. These results imply that pachyerosin may be used as a new promising anticancer agent. Georg Thieme Verlag KG Stuttgart · New York.

Live Cell Imaging Reveals Differential Modifications to Cytoplasmic Dynein Properties by Phospho- and Dephospho-mimic Mutations of the Intermediate Chain 2C S84

PubMed Central

Blasier, Kiev R.; Humsi, Michael K.; Ha, Junghoon; Ross, Mitchell W.; Smiley, W. Russell; Inamdar, Nirja A.; Mitchell, David J.; Lo, Kevin W.-H.; Pfister, K. Kevin

2014-01-01

Cytoplasmic dynein is a multi-subunit motor protein responsible for intracellular cargo transport toward microtubule minus ends. There are multiple isoforms of the dynein intermediate chain (DYNC1I, IC) which is encoded by two genes. One way to regulate cytoplasmic dynein is by IC phosphorylation. The IC-2C isoform is expressed in all cells and the functional significance of phosphorylation on IC-2C serine 84 was investigated using live cell imaging of fluorescent protein-tagged wild type IC-2C (WT) and phospho- and dephospho-mimic mutant isoforms in axonal transport model systems. Both mutations modulated dynein functional properties. The dephospho-mimic mutant IC-2C S84A had greater co-localization with mitochondria than IC-2C wild-type (WT) or the phospho-mimic mutant IC-2C S84D. The dephospho-mimic mutant IC-2C S84A was also more likely to be motile than the phospho-mimic mutant IC-2C S84D or IC-2C WT. In contrast, the phospho-mimic mutant IC-2C S84D mutant was more likely to move in the retrograde direction than was the IC-2C S84A mutant. The phospho-mimic IC-2C S84D was also as likely as IC-2C WT to co-localize with mitochondria. Both the S84D phospho- and S84A, dephospho-mimic mutants were found to be capable of microtubule minus end directed (retrograde) movement in axons. They were also observed to be passively transported in the anterograde direction. These data suggest that the IC-2C S84 has a role in modulating dynein properties. PMID:24798412

Average chest wall thickness at two anatomic locations in trauma patients.

PubMed

Schroeder, Elizabeth; Valdez, Carrie; Krauthamer, Andres; Khati, Nadia; Rasmus, Jessica; Amdur, Richard; Brindle, Kathleen; Sarani, Babak

2013-09-01

Needle thoracostomy is the emergent treatment for tension pneumothorax. This procedure is commonly done using a 4.5cm catheter, and the optimal site for chest wall puncture is controversial. We hypothesize that needle thoracostomy cannot be performed using this catheter length irrespective of the site chosen in either gender. A retrospective review of all chest computed tomography (CT) scans obtained on trauma patients from January 1, 2011 to December 31, 2011 was performed. Patients aged 18 and 80 years were included and patients whose chest wall thickness exceeded the boundary of the images acquired were excluded. Chest wall thickness was measured at the 2nd intercostal (ICS), midclavicular line (MCL) and the 5th ICS, anterior axillary line (AAL). Injury severity score (ISS), chest wall thickness, and body mass index (BMI) were analyzed. 201 patients were included, 54% male. Average (SD) BMI was 26 (7)kg/m(2). The average chest wall thickness in the overall cohort was 4.08 (1.4)cm at the 2nd ICS/MCL and 4.55 (1.7)cm at the 5th ICS/AAL. 29% of the overall cohort (27 male and 32 female) had a chest wall thickness greater than 4.5cm at the 2nd ICS/MCL and 45% (54 male and 36 female) had a chest wall thickness greater than 4.5cm at the 5th ICS/AAL. There was no significant interaction between gender and chest wall thickness at either site. BMI was positively associated with chest wall thickness at both the 2nd and 5th ICS/AAL. A 4.5cm catheter is inadequate for needle thoracostomy in most patients regardless of puncture site or gender. Copyright © 2013 Elsevier Ltd. All rights reserved.

Sensitivity recovery for the AX-PET prototype using inter-crystal scattering events

NASA Astrophysics Data System (ADS)

Gillam, John E.; Solevi, Paola; Oliver, Josep F.; Casella, Chiara; Heller, Matthieu; Joram, Christian; Rafecas, Magdalena

2014-08-01

The development of novel detection devices and systems such as the AX-positron emission tomography (PET) demonstrator often introduce or increase the measurement of atypical coincidence events such as inter-crystal scattering (ICS). In more standard systems, ICS events often go undetected and the small measured fraction may be ignored. As the measured quantity of such events in the data increases, so too does the importance of considering them during image reconstruction. Generally, treatment of ICS events will attempt to determine which of the possible candidate lines of response (LoRs) correctly determine the annihilation photon trajectory. However, methods of assessment often have low success rates or are computationally demanding. In this investigation alternative approaches are considered. Experimental data was taken using the AX-PET prototype and a NEMA phantom. Three methods of ICS treatment were assessed—each of which considered all possible candidate LoRs during image reconstruction. Maximum likelihood expectation maximization was used in conjunction with both standard (line-like) and novel (V-like in this investigation) detection responses modeled within the system matrix. The investigation assumed that no information other than interaction locations was available to distinguish between candidates, yet the methods assessed all provided means by which such information could be included. In all cases it was shown that the signal to noise ratio is increased using ICS events. However, only one method, which used full modeling of the ICS response in the system matrix—the V-like model—provided enhancement in all figures of merit assessed in this investigation. Finally, the optimal method of ICS incorporation was demonstrated using data from two small animals measured using the AX-PET demonstrator.

A study of H-alpha velocities in NGC 1499, NGC 7000, and IC 1318B/C

NASA Technical Reports Server (NTRS)

Fountain, W. F.; Gary, G. A.; Odell, C. R.

1983-01-01

Multiple slit echelle spectrograph observations of the H-alpha emission line are used to map the radial velocities of the California Nebula (NGC 1499), the North American Nebula complex (NGC 7000 and IC 5070), and IC 1318B/C. The California Nebula is singularly constant in velocity, considering its geometry. The North American Nebula complex reflects a very simple, classical dynamical picture. The expansion discovered earlier in IC 1318B/C is confirmed, detailed, and the model refined. The new data, along with that in earlier papers of this series, show that stellar wind acceleration and champagne flow mechanisms both play important roles in determining the evolution of H II regions.

Synthesis and in vitro anti-proliferative effects of 3-(hetero)aryl substituted 3-[(prop-2-ynyloxy)(thiophen-2-yl)methyl]pyridine derivatives on various cancer cell lines.

PubMed

Reddy Chamakura, Upendar; Sailaja, E; Dulla, Balakrishna; Kalle, Arunasree M; Bhavani, S; Rambabu, D; Kapavarapu, Ravikumar; Rao, M V Basaveswara; Pal, Manojit

2014-03-01

A series of 3-(hetero)aryl substituted 3-[(prop-2-ynyloxy)(thiophen-2-yl)methyl]pyridine derivatives were designed as potential anticancer agents. These compounds were conveniently prepared by using Pd/C-Cu mediated Sonogashira type coupling as a key step. Many of these compounds were found to be promising when tested for their in vitro anti-proliferative properties against six cancer cell lines. All these compounds were found to be selective towards the growth inhibition of cancer cells with IC50 values in the range of 0.9-1.7 μM (against MDA-MB 231 and MCF7 cells), comparable to the known anticancer drug doxorubicin. Copyright © 2014 Elsevier Ltd. All rights reserved.

Targeted Induction of Interferon-λ in Humanized Chimeric Mouse Liver Abrogates Hepatotropic Virus Infection

PubMed Central

Kameyama, Takeshi; Tokunaga, Yuko; Nishito, Yasumasa; Hirabayashi, Kazuko; Yano, Junichi; Ochiya, Takahiro; Tateno, Chise; Tanaka, Yasuhito; Mizokami, Masashi; Tsukiyama-Kohara, Kyoko; Inoue, Kazuaki; Yoshiba, Makoto; Takaoka, Akinori; Kohara, Michinori

2013-01-01

Background & Aims The interferon (IFN) system plays a critical role in innate antiviral response. We presume that targeted induction of IFN in human liver shows robust antiviral effects on hepatitis C virus (HCV) and hepatitis B virus (HBV). Methods This study used chimeric mice harboring humanized livers and infected with HCV or HBV. This mouse model permitted simultaneous analysis of immune responses by human and mouse hepatocytes in the same liver and exploration of the mechanism of antiviral effect against these viruses. Targeted expression of IFN was induced by treating the animals with a complex comprising a hepatotropic cationic liposome and a synthetic double-stranded RNA analog, pIC (LIC-pIC). Viral replication, IFN gene expression, IFN protein production, and IFN antiviral activity were analyzed (for type I, II and III IFNs) in the livers and sera of these humanized chimeric mice. Results Following treatment with LIC-pIC, the humanized livers of chimeric mice exhibited increased expression (at the mRNA and protein level) of human IFN-λs, resulting in strong antiviral effect on HBV and HCV. Similar increases were not seen for human IFN-α or IFN-β in these animals. Strong induction of IFN-λs by LIC-pIC occurred only in human hepatocytes, and not in mouse hepatocytes nor in human cell lines derived from other (non-hepatic) tissues. LIC-pIC-induced IFN-λ production was mediated by the immune sensor adaptor molecules mitochondrial antiviral signaling protein (MAVS) and Toll/IL-1R domain-containing adaptor molecule-1 (TICAM-1), suggesting dual recognition of LIC-pIC by both sensor adaptor pathways. Conclusions These findings demonstrate that the expression and function of various IFNs differ depending on the animal species and tissues under investigation. Chimeric mice harboring humanized livers demonstrate that IFN-λs play an important role in the defense against human hepatic virus infection. PMID:23555725

Targeted induction of interferon-λ in humanized chimeric mouse liver abrogates hepatotropic virus infection.

PubMed

Nakagawa, Shin-ichiro; Hirata, Yuichi; Kameyama, Takeshi; Tokunaga, Yuko; Nishito, Yasumasa; Hirabayashi, Kazuko; Yano, Junichi; Ochiya, Takahiro; Tateno, Chise; Tanaka, Yasuhito; Mizokami, Masashi; Tsukiyama-Kohara, Kyoko; Inoue, Kazuaki; Yoshiba, Makoto; Takaoka, Akinori; Kohara, Michinori

2013-01-01

The interferon (IFN) system plays a critical role in innate antiviral response. We presume that targeted induction of IFN in human liver shows robust antiviral effects on hepatitis C virus (HCV) and hepatitis B virus (HBV). This study used chimeric mice harboring humanized livers and infected with HCV or HBV. This mouse model permitted simultaneous analysis of immune responses by human and mouse hepatocytes in the same liver and exploration of the mechanism of antiviral effect against these viruses. Targeted expression of IFN was induced by treating the animals with a complex comprising a hepatotropic cationic liposome and a synthetic double-stranded RNA analog, pIC (LIC-pIC). Viral replication, IFN gene expression, IFN protein production, and IFN antiviral activity were analyzed (for type I, II and III IFNs) in the livers and sera of these humanized chimeric mice. Following treatment with LIC-pIC, the humanized livers of chimeric mice exhibited increased expression (at the mRNA and protein level) of human IFN-λs, resulting in strong antiviral effect on HBV and HCV. Similar increases were not seen for human IFN-α or IFN-β in these animals. Strong induction of IFN-λs by LIC-pIC occurred only in human hepatocytes, and not in mouse hepatocytes nor in human cell lines derived from other (non-hepatic) tissues. LIC-pIC-induced IFN-λ production was mediated by the immune sensor adaptor molecules mitochondrial antiviral signaling protein (MAVS) and Toll/IL-1R domain-containing adaptor molecule-1 (TICAM-1), suggesting dual recognition of LIC-pIC by both sensor adaptor pathways. These findings demonstrate that the expression and function of various IFNs differ depending on the animal species and tissues under investigation. Chimeric mice harboring humanized livers demonstrate that IFN-λs play an important role in the defense against human hepatic virus infection.

Dihydroartemisinin increases temozolomide efficacy in glioma cells by inducing autophagy

PubMed Central

ZHANG, ZE-SHUN; WANG, JING; SHEN, YOU-BI; GUO, CHENG-CHENG; SAI, KE; CHEN, FU-RONG; MEI, XIN; HAN, FU; CHEN, ZHONG-PING

2015-01-01

Artemisinin, a powerful antimalarial medicine, is extracted from the Chinese herb, Artemisia annua L., and has the ability to inhibit the proliferation of cancer cells. Dihydroartemisinin (DHA), the major active metabolite of artemisinin, is able to inhibit the growth of a variety of types of human cancer. However, the effect of DHA on human glioma cells remains unclear. The aim of the present study was to investigate the effect of DHA on the proliferation of glioma cells, and whether DHA was able to enhance temozolomide (TMZ) sensitivity in vitro and in vivo. In total, 10 human glioma cell lines were used to analyze the growth inhibition ability of DHA by MTT assay. The typical autophagic vacuoles were monitored by the application of the autofluorescent agent, monodansylcadaverine. Western blotting was used to detect markers of apoptosis and autophagy, namely Caspase-3, Beclin-1 and LC3-B. The combination efficiency of DHA and TMZ was assessed in vitro and in vivo. The half maximal inhibitory concentration (IC50) of DHA differed among the ten human glioma cell lines. The number of autophagic vacuoles was higher in DHA-treated SKMG-4 cells; this was highest of all cell lines analyzed. The expression of autophagy molecular markers, Beclin-1 and LC3-B, was increased following DHA treatment, while no significant alteration was detected in the expression of apoptotic marker Caspase-3. When combined with DHA, the IC50 of TMZ decreased significantly in the four glioma cell lines analyzed. Furthermore, DHA enhanced the tumor inhibition ability of TMZ in tumor-burdened mice. The results of the present study demonstrated that DHA inhibited the proliferation of glioma cells and enhanced the tumor inhibition efficacy of TMZ in vitro and in vivo through the induction of autophagy. PMID:26171034

Broad and potent HIV-1 neutralization by a human antibody that binds the gp41-120 interface

PubMed Central

Huang, Jinghe; Kang, Byong H.; Pancera, Marie; Lee, Jeong Hyun; Tong, Tommy; Feng, Yu; Georgiev, Ivelin S.; Chuang, Gwo-Yu; Druz, Aliaksandr; Doria-Rose, Nicole A.; Laub, Leo; Sliepen, Kwinten; van Gils, Marit J.; de la Peña, Alba Torrents; Derking, Ronald; Klasse, Per-Johan; Migueles, Stephen A.; Bailer, Robert T.; Alam, Munir; Pugach, Pavel; Haynes, Barton F.; Wyatt, Richard T.; Sanders, Rogier W.; Binley, James M.; Ward, Andrew B.; Mascola, John R.; Kwong, Peter D.; Connors, Mark

2014-01-01

The isolation of human monoclonal antibodies (mAbs) is providing important insights regarding the specificities that underlie broad neutralization of HIV-1 (reviewed in1). Here we report a broad and extremely potent HIV-specific mAb, termed 35O22, which binds novel HIV-1 envelope glycoprotein (Env) epitope. 35O22 neutralized 62% of 181 pseudoviruses with an IC50<50 μg/ml. The median IC50 of neutralized viruses was 0.033 μg/ml, among the most potent thus far described. 35O22 did not bind monomeric forms of Env tested, but did bind the trimeric BG505 SOSIP.664. Mutagenesis and a reconstruction by negative-stain electron microscopy of the Fab in complex with trimer revealed it to bind a conserved epitope, which stretched across gp120 and gp41. The specificity of 35O22 represents a novel site of vulnerability on HIV Env, which serum analysis indicates to be commonly elicited by natural infection. Binding to this new site of vulnerability may thus be an important complement to current mAb-based approaches to immunotherapies, prophylaxis, and vaccine design. PMID:25186731

In vitro antiproliferative/cytotoxic activity on cancer cell lines of a cardanol and a cardol enriched from Thai Apis mellifera propolis

PubMed Central

2012-01-01

Background Propolis is a complex resinous honeybee product. It is reported to display diverse bioactivities, such as antimicrobial, anti-inflammatory and anti-tumor properties, which are mainly due to phenolic compounds, and especially flavonoids. The diversity of bioactive compounds depends on the geography and climate, since these factors affect the floral diversity. Here, Apis mellifera propolis from Nan province, Thailand, was evaluated for potential anti-cancer activity. Methods Propolis was sequentially extracted with methanol, dichloromethane and hexane and the cytotoxic activity of each crude extract was assayed for antiproliferative/cytotoxic activity in vitro against five human cell lines derived from duet carcinoma (BT474), undifferentiated lung (Chaco), liver hepatoblastoma (Hep-G2), gastric carcinoma (KATO-III) and colon adenocarcinoma (SW620) cancers. The human foreskin fibroblast cell line (Hs27) was used as a non-transformed control. Those crude extracts that displayed antiproliferative/cytotoxic activity were then further fractionated by column chromatography using TLC-pattern and MTT-cytotoxicity bioassay guided selection of the fractions. The chemical structure of each enriched bioactive compound was analyzed by nuclear magnetic resonance and mass spectroscopy. Results The crude hexane and dichloromethane extracts of propolis displayed antiproliferative/cytotoxic activities with IC50 values across the five cancer cell lines ranging from 41.3 to 52.4 μg/ml and from 43.8 to 53.5 μg/ml, respectively. Two main bioactive components were isolated, one cardanol and one cardol, with broadly similar in vitro antiproliferation/cytotoxicity IC50 values across the five cancer cell lines and the control Hs27 cell line, ranging from 10.8 to 29.3 μg/ml for the cardanol and < 3.13 to 5.97 μg/ml (6.82 - 13.0 μM) for the cardol. Moreover, both compounds induced cytotoxicity and cell death without DNA fragmentation in the cancer cells, but only an antiproliferation response in the control Hs27 cells However, these two compounds did not account for the net antiproliferation/cytotoxic activity of the crude extracts suggesting the existence of other potent compounds or synergistic interactions in the propolis extracts. Conclusion This is the first report that Thai A. mellifera propolis contains at least two potentially new compounds (a cardanol and a cardol) with potential anti-cancer bioactivity. Both could be alternative antiproliferative agents for future development as anti-cancer drugs. PMID:22458642

Three new labdane-type diterpene glycosides from fruits of Rubus chingii and their cytotoxic activities against five humor cell lines.

PubMed

Zhong, Ruijian; Guo, Qing; Zhou, Guoping; Fu, Huizheng; Wan, Kaihua

2015-04-01

Three new labdane-type diterpene glycosides, 15,18-di-O-β-d-glucopyranosyl-13(E)-ent-labda-7(8),13(14)-diene-3β,15,18-triol (1), 15,18-di-O-β-d-glucopyranosyl-13(E)-ent-labda-8(9),13(14)-diene-3β,15,18-triol (2), and 15-O-β-d-apiofuranosyl-(1→2)-β-d-glucopyranosyl-18-O-β-d-glucopyranosyl-13(E)-ent-labda-8(9),13(14)-diene-3β,15,18-triol (3), were isolated from the fruits of Rubus chingii. Their structures were elucidated on the basis of spectroscopic data and chemical methods. The cytotoxic activities of compounds 1-3 were evaluated against five human tumor cell lines (HCT-8, BGC-823, A549, and A2780). Compounds 3 showed cytotoxic activity against A549 with an IC50 value of 2.32μM. Crown Copyright © 2015. Published by Elsevier B.V. All rights reserved.

Multivalent dendrimeric compounds containing carbohydrates expressed on immune cells inhibit infection by primary isolates of HIV-1

PubMed Central

Borges, Andrew Rosa; Wieczorek, Lindsay; Johnson, Benitra; Benesi, Alan J.; Brown, Bruce K.; Kensinger, Richard D.; Krebs, Fred C.; Wigdahl, Brian; Blumenthal, Robert; Puri, Anu; McCutchan, Francine E.; Birx, Deborah L.; Polonis, Victoria R.; Schengrund, Cara-Lynne

2010-01-01

Specific glycosphingolipids (GSL), found on the surface of target immune cells, are recognized as alternate cell surface receptors by the human immunodeficiency virus type 1 (HIV-1) external envelope glycoprotein. In this study, the globotriose and 3’-sialyllactose carbohydrate head groups found on two GSL were covalently attached to a dendrimer core to produce two types of unique multivalent carbohydrates (MVC). These MVC inhibited HIV-1 infection of T cell lines and primary peripheral blood mononuclear cells (PBMC) by T cell line-adapted viruses or primary isolates, with IC50s ranging from 0.1 – 7.4 µg/ml. Inhibition of Env-mediated membrane fusion by MVC was also observed using a dye-transfer assay. These carbohydrate compounds warrant further investigation as a potential new class of HIV-1 entry inhibitors. The data presented also shed light on the role of carbohydrate moieties in HIV-1 virus-host cell interactions. PMID:20880566

Correlation of the ionisation response at selected points of IC sensitive regions with SEE sensitivity parameters under pulsed laser irradiation

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

Gordienko, A V; Mavritskii, O B; Egorov, A N

2014-12-31

The statistics of the ionisation response amplitude measured at selected points and their surroundings within sensitive regions of integrated circuits (ICs) under focused femtosecond laser irradiation is obtained for samples chosen from large batches of two types of ICs. A correlation between these data and the results of full-chip scanning is found for each type. The criteria for express validation of IC single-event effect (SEE) hardness based on ionisation response measurements at selected points are discussed. (laser applications and other topics in quantum electronics)

BLACK HOLE MASS AND EDDINGTON RATIO DISTRIBUTION FUNCTIONS OF X-RAY-SELECTED BROAD-LINE AGNs AT z {approx} 1.4 IN THE SUBARU XMM-NEWTON DEEP FIELD

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

Nobuta, K.; Akiyama, M.; Ueda, Y.

2012-12-20

In order to investigate the growth of supermassive black holes (SMBHs), we construct the black hole mass function (BHMF) and Eddington ratio distribution function (ERDF) of X-ray-selected broad-line active galactic nuclei (AGNs) at z {approx} 1.4 in the Subaru XMM-Newton Deep Survey (SXDS) field. A significant part of the accretion growth of SMBHs is thought to take place in this redshift range. Black hole masses of X-ray-selected broad-line AGNs are estimated using the width of the broad Mg II line and 3000 A monochromatic luminosity. We supplement the Mg II FWHM values with the H{alpha} FWHM obtained from our NIRmore » spectroscopic survey. Using the black hole masses of broad-line AGNs at redshifts between 1.18 and 1.68, the binned broad-line AGN BHMFs and ERDFs are calculated using the V{sub max} method. To properly account for selection effects that impact the binned estimates, we derive the corrected broad-line AGN BHMFs and ERDFs by applying the maximum likelihood method, assuming that the ERDF is constant regardless of the black hole mass. We do not correct for the non-negligible uncertainties in virial BH mass estimates. If we compare the corrected broad-line AGN BHMF with that in the local universe, then the corrected BHMF at z = 1.4 has a higher number density above 10{sup 8} M{sub Sun} but a lower number density below that mass range. The evolution may be indicative of a downsizing trend of accretion activity among the SMBH population. The evolution of broad-line AGN ERDFs from z = 1.4 to 0 indicates that the fraction of broad-line AGNs with accretion rates close to the Eddington limit is higher at higher redshifts.« less

Stellar Photometric Structures of the Host Galaxies of Nearby Type 1 Active Galactic Nuclei

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

Kim, Minjin; Ho, Luis C.; Peng, Chien Y.

2017-10-01

We present detailed image analysis of rest-frame optical images of 235 low-redshift ( z ≲ 0.35) Type 1 active galactic nuclei (AGNs) observed with the Hubble Space Telescope . The high-resolution images enable us to perform rigorous two-dimensional image modeling to decouple the luminous central point source from the host galaxy, which, when warranted, is further decomposed into its principal structural components (bulge, bar, and disk). In many cases, care must be taken to account for structural complexities such as spiral arms, tidal features, and overlapping or interacting companion galaxies. We employ Fourier modes to characterize the degree of asymmetrymore » of the light distribution of the stars as a quantitative measure of morphological distortion due to interactions or mergers. We examine the dependence of the physical parameters of the host galaxies on the properties of the AGNs, namely, radio-loudness and the width of the broad emission lines. In accordance with previous studies, narrow-line (H β FWHM ≤ 2000 km s{sup −1}) Type 1 AGNs, in contrast to their broad-line (H β FWHM > 2000 km s{sup −1}) counterparts, are preferentially hosted in later-type, lower-luminosity galaxies, which have a higher incidence of pseudo-bulges, are more frequently barred, and are less morphologically disturbed. This suggests that narrow-line Type 1 AGNs experienced a more quiescent evolutionary history driven primarily by internal secular evolution instead of external dynamical perturbations. The fraction of AGN hosts showing merger signatures is larger for more luminous sources. Radio-loud AGNs generally preferentially live in earlier-type (bulge-dominated), more massive hosts, although a minority of them appear to contain a significant disk component. We do not find convincing evidence for enhanced merger signatures in the radio-loud population.« less

MICROLENSING OF QUASAR BROAD EMISSION LINES: CONSTRAINTS ON BROAD LINE REGION SIZE

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

Guerras, E.; Mediavilla, E.; Jimenez-Vicente, J.

2013-02-20

We measure the differential microlensing of the broad emission lines between 18 quasar image pairs in 16 gravitational lenses. We find that the broad emission lines are in general weakly microlensed. The results show, at a modest level of confidence (1.8{sigma}), that high ionization lines such as C IV are more strongly microlensed than low ionization lines such as H{beta}, indicating that the high ionization line emission regions are more compact. If we statistically model the distribution of microlensing magnifications, we obtain estimates for the broad line region size of r{sub s} = 24{sup +22} {sub -15} and r{sub s}more » = 55{sup +150} {sub -35} lt-day (90% confidence) for the high and low ionization lines, respectively. When the samples are divided into higher and lower luminosity quasars, we find that the line emission regions of more luminous quasars are larger, with a slope consistent with the expected scaling from photoionization models. Our estimates also agree well with the results from local reveberation mapping studies.« less

Evaluation of Cytarabine Against Ewing Sarcoma Xenografts by the Pediatric Preclinical Testing Program

PubMed Central

Houghton, Peter J.; Morton, Christopher L.; Kang, Min; Reynolds, C. Patrick; Billups, Catherine A.; Favours, Edward; Payne-Turner, Debbie; Tucker, Chandra; Smith, Malcolm A.

2015-01-01

Treatment with the nucleoside analog cytarabine has been shown to mimic changes in gene expression associated with down-regulation of the EWS-FLI1 oncogene in Ewing sarcoma cell lines, selectively inhibit their growth in vitro, and cause tumor regression in athymic nude mice. For this report cytarabine was studied in vitro against a panel of 23 pediatric cancer cell lines and in vivo against 6 Ewing sarcoma xenografts. Acute lymphoblastic leukemia cell lines were the most sensitive to cytarabine in vitro (median IC50 9 nM), while Ewing sarcoma cell lines showed intermediate sensitivity (median IC50 232 nM). Cytarabine at a dose of 150 mg/kg administered daily 5× failed to significantly inhibit growth of five xenograft models, but reduced growth rate of the A673 xenograft by 50%. Cytarabine shows no differential in vitro activity against Ewing sarcoma cell lines and is ineffective in vivo against Ewing sarcoma xenografts at the dose and schedule studied. PMID:20979180

Cytotoxic activity screening of Bangladeshi medicinal plant extracts.

PubMed

Akter, Raushanara; Uddin, Shaikh J; Grice, I Darren; Tiralongo, Evelin

2014-01-01

The cytotoxic activity of 23 crude methanol extracts from 19 Bangladeshi medicinal plants was investigated against healthy mouse fibroblasts (NIH3T3), healthy monkey kidney (VERO) and four human cancer cell lines (gastric, AGS; colon, HT-29; and breast, MCF-7 and MDA-MB-231) using MTT assay. High cytotoxicity across all cell lines tested was exhibited by Aegiceras corniculatum (fruit) and Hymenodictyon excelsum (bark) extracts (IC50 values ranging from 0.0005 to 0.9980 and 0.08 to 0.44 mg/mL, respectively). Fourteen extracts from 11 plant species, namely Clitoria ternatea (flower and leaf), Dillenia indica (leaf), Diospyros peregrina (leaf), Dipterocarpus turbinatus (bark and leaf), Ecbolium viride (leaf), Glinus oppositifolius (whole plant), Gnaphalium luteoalbum (leaf), Jasminum sambac (leaf), Lannea coromandelica (bark and leaf), Mussaenda glabrata (leaf) and Saraca asoca (leaf), were also significantly cytotoxic (IC50 < 1.0 mg/mL) against at least one of the cancer cell lines tested. More selectively, Avicennia alba (leaf), C. ternatea (flower and leaf), Caesalpinia pulcherrima (leaf), E. viride (leaf) and G. oppositifolius (whole plant) showed cytotoxicity only against both of the breast cancer cell lines (MCF-7 and MDA-MB-231). In contrast, C. ternatea (flower and leaf) exhibited high cytotoxic activity against MDA-MB-231 (IC50 values of 0.11 and 0.49 mg/mL, respectively), whereas E. viride and G. oppositifolius whole plant extracts exhibited high activity against MCF-7 cells (IC50 values of 0.06 and 0.15 mg/mL, respectively). The cytotoxic activity test results for 9 of the plant species correlate with their traditional use as anticancer agents, thus making them interesting sources for further drug development.

Photoionization Modelling of the Giant Broad-Line Region in NGC 3998.

NASA Astrophysics Data System (ADS)

Devereux, Nicholas

2018-01-01

Prior high angular resolution spectroscopic observations of the low-ionization nuclear emission-line region in NGC 3998 obtained with the Space Telescope Imaging Spectrograph aboard the Hubble Space Telescope revealed a rich UV-visible spectrum consisting of broad permitted and broad forbidden emission lines. The photoionization code XSTAR is employed together with reddening-insensitive emission line diagnostics to constrain a dynamical model for the broad-line region (BLR) in NGC 3998. The BLR is modelled as a large H+ region ~ 7 pc in radius consisting of dust-free, low density ~ 104 cm-3, low metallicity ~ 0.01 Z/Z⊙ gas. Modelling the shape of the broad Hα emission line significantly discriminates between two independent measures of the black hole mass, favouring the estimate of de Francesco (2006). Interpreting the broad Hα emission line in terms of a steady-state spherically symmetric inflow leads to a mass inflow rate of 1.4 x 10-2 M⊙/yr, well within the present uncertainty of calculations that attempt to explain the observed X-ray emission in terms of an advection-dominated accretion flow (ADAF). Collectively, the model provides an explanation for the shape of the Hα emission line, the relative intensities and luminosities for the H Balmer, [OIII], and potentially several of the broad UV emission lines, as well as refining the initial conditions needed for future modelling of the ADAF.

From COX-2 inhibitor nimesulide to potent anti-cancer agent: synthesis, in vitro, in vivo and pharmacokinetic evaluation

PubMed Central

Chennamaneni, Snigdha; Yi, Xin; Liu, lili; Pink, John J.; Dowlati, Afshin; Xu, Yan; Zhou, Aimin; Su, Bin

2014-01-01

Cyclooxygenase-2 (COX-2) inhibitor nimesulide inhibits the proliferation of various types of cancer cells mainly via COX-2 independent mechanisms, which makes it a good lead compound for anti-cancer drug development. In the presented study, a series of new nimesulide analogs were synthesized based on the structure–function analysis generated previously. Some of them displayed very potent anti-cancer activity with IC50s around 100nM to 200nM to inhibit SKBR-3 breast cancer cell growth. CSUOH0901 (NSC751382) from the compound library also inhibits the growth of the 60 cancer cell lines used at National Cancer Institute Developmental therapeutics Program (NCIDTP) with IC50s around 100nM to 500nM. Intraperitoneal injection with a dosage of 5mg/kg/d of CSUOH0901 to nude mice suppresses HT29 colorectal xenograft growth. Pharmacokinetic studies demonstrate the good bioavailability of the compound. PMID:22119125

Design, synthesis and anti-tumor activity study of novel histone deacetylase inhibitors containing isatin-based caps and o-phenylenediamine-based zinc binding groups.

PubMed

Gao, Shuai; Zang, Jie; Gao, Qianwen; Liang, Xuewu; Ding, Qinge; Li, Xiaoyang; Xu, Wenfang; Chou, C James; Zhang, Yingjie

2017-06-15

As a hot topic of epigenetic studies, histone deacetylases (HDACs) are related to lots of diseases, especially cancer. Further researches indicated that different HDAC isoforms played various roles in a wide range of tumor types. Herein a novel series of HDAC inhibitors with isatin-based caps and o-phenylenediamine-based zinc binding groups have been designed and synthesized through scaffold hopping strategy. Among these compounds, the most potent compound 9n exhibited similar if not better HDAC inhibition and antiproliferative activities against multiple tumor cell lines compared with the positive control entinostat (MS-275). Additionally, compared with MS-275 (IC 50 values for HDAC1, 2 and 3 were 0.163, 0.396 and 0.605µM, respectively), compound 9n with IC 50 values of 0.032, 0.256 and 0.311µM for HDAC1, 2 and 3 respectively, showed a moderate HDAC1 selectivity. Copyright © 2017. Published by Elsevier Ltd.

Why Flash Type Matters: A Statistical Analysis

NASA Astrophysics Data System (ADS)

Mecikalski, Retha M.; Bitzer, Phillip M.; Carey, Lawrence D.

2017-09-01

While the majority of research only differentiates between intracloud (IC) and cloud-to-ground (CG) flashes, there exists a third flash type, known as hybrid flashes. These flashes have extensive IC components as well as return strokes to ground but are misclassified as CG flashes in current flash type analyses due to the presence of a return stroke. In an effort to show that IC, CG, and hybrid flashes should be separately classified, the two-sample Kolmogorov-Smirnov (KS) test was applied to the flash sizes, flash initiation, and flash propagation altitudes for each of the three flash types. The KS test statistically showed that IC, CG, and hybrid flashes do not have the same parent distributions and thus should be separately classified. Separate classification of hybrid flashes will lead to improved lightning-related research, because unambiguously classified hybrid flashes occur on the same order of magnitude as CG flashes for multicellular storms.

The BAT AGN Spectroscopic Survey (BASS)

NASA Astrophysics Data System (ADS)

Koss, Michael; Trakhtenbrot, Benny; Ricci, Claudio; Lamperti, Isabella; Oh, Kyuseok; Berney, Simon; Schawinski, Kevin; Balokovic, Mislav; Baronchelli, Linda; Gehrels, Neil; Stern, Daniel; Mushotzky, Richard; Veilleux, Sylvain; Ueda, Yoshihiro; Crenshaw, D. Michael; Harrison, Fiona; Fischer, Travis C.; Treister, Ezequiel; BASS Team; Swift BAT Team

2017-01-01

We present the Swift BAT AGN Spectroscopic Survey (BASS) and discus the first four papers. The catalog represents an unprecedented census of hard-X-ray selected AGN in the local universe, with ~90% of sources at z<0.2. Starting from an all-sky catalog of AGN detected based on their 14-195 keV flux from the 70-month Swift/BAT catalog, we analyze a total of 1279 optical spectra, taken from twelve dierent telescopes, for a total of 642 spectra of unique AGN. We present the absorption and emission line measurements as well as black hole masses and accretion rates for the majority of obscured and un-obscured AGN (473), representing more than a factor of 10 increase from past studies. Consistent with previous surveys, we find an increase in the fraction of un-obscured (type 1) AGN, as measured from broad Hbeta and Halpha, with increasing 14-195 keV and 2-10 keV luminosity. We find the FWHM of the emission lines to show broad agreement with the X-ray obscuration measurements. Compared to narrow line AGN in the SDSS, the X-ray selected AGN in our sample with emission lines have a larger fraction of dustier galaxies suggesting these types of galaxies are missed in optical AGN surveys using emission line diagnostics. Additionally, we discuss follow-on efforts to study the variation of [OIII] to Xray measurements, a new method to measure accretion rates from using line ratios, a sample of 100 AGN observed with NIR spectroscopy, and an effort to measure the accretion rates and obscuration with merger stage in a subsample of mergers.

Correlation between the line width and the line flux of the double-peaked broad Hα of 3C390.3

NASA Astrophysics Data System (ADS)

Zhang, Xue-Guang

2013-03-01

In this paper, we carefully check the correlation between the line width (second moment) and the line flux of the double-peaked broad Hα of the well-known mapped active galactic nucleus (AGN) 3C390.3 in order to show some further distinctions between double-peaked emitters and normal broad-line AGN. Based on the virialization assumption MBH ∝ RBLR × V2(BLR) and the empirical relation RBLR ∝ L˜0.5, one strong negative correlation between the line width and the line flux of the double-peaked broad lines should be expected for 3C390.3, such as the negative correlation confirmed for the mapped broad-line object NGC 5548, RBLR × V2(BLR) ∝ L˜0.5 × σ2 = constant. Moreover, based on the public spectra around 1995 from the AGN WATCH project for 3C390.3, one reliable positive correlation is found between the line width and the line flux of the double-peaked broad Hα. In the context of the proposed theoretical accretion disc model for double-peaked emitters, the unexpected positive correlation can be naturally explained, due to different time delays for the inner and outer parts of the disc-like broad-line region (BLR) of 3C390.3. Moreover, the virialization assumption is checked and found to be still available for 3C390.3. However, the time-varying size of the BLR of 3C390.3 cannot be expected by the empirical relation RBLR ∝ L˜0.5. In other words, the mean size of the BLR of 3C390.3 can be estimated by the continuum luminosity (line luminosity), while the continuum emission strengthening leads to the size of BLR decreasing (not increasing) in different moments for 3C390.3. Then, we compared our results of 3C390.3 with the previous results reported in the literature for the other double-peaked emitters, and found that before to clearly correct the effects from disc physical parameters varying (such as the effects of disc precession) for long-term observed line spectra, it is not so meaningful to discuss the correlation of the line parameters of double-peaked broad lines. Furthermore, due to the probable `external' ionizing source with so far unclear structures, it is hard to give one conclusion that the positive correlation between the line width and the line flux can be found for all double-peaked emitters, even after the considerations of disc physical parameters varying. However, once one positive correlation of broad-line parameters is found, the accretion disc origination of the broad line should be considered first.

[Establishment of Z-HL16C cell line.].

PubMed

Chen, J P; Li, J; Zhao, S L; Tian, J Y; Ye, F

2006-09-01

To establish and study the nature and the application of Z-HL16C cell line. The cell line was continuously passed, frozen stored and recovered. Its application was expanded and the cell type was identified. The cell line had an epithelial-cell-like shape, the size appeared uniform, the cell boundary was distinct. It has been continuously passed, frozen stored and recovered for ten years. Its recovery rate was about 90%. It has been proved to be sensitive to the tested viruses which were enteroviruses (Polio, Cox, Echo), influenza viruses, parainfluenzaviruses, adenoviruses, measles virus. This cell line has been identified as a cancerization cell. The cell line Z-HL16C has been stably established, it has a broad spectrum in sensitivity for culturing viruses.

A novel vaccine against Porcine circovirus type 2 (PCV2) and Streptococcus equi ssp. zooepidemicus (SEZ) co-infection.

PubMed

Lin, Hui-xing; Ma, Zhe; Yang, Xu-qiu; Fan, Hong-jie; Lu, Cheng-ping

2014-06-25

To develop a vaccine against Porcine circovirus type 2 (PCV2) and Streptococcus equi ssp. zooepidemicus (SEZ) co-infection, the genes of porcine IL-18, capsid protein (Cap) of PCV2 and M-like protein (SzP) of SEZ were inserted into the swinepox virus (SPV) genome by homologous recombination. The recombinant swinepox virus rSPV-ICS was verified by PCR and indirect immunofluorescence assays. To evaluate the immunogenicity of rSPV-ICS, 28 PCV2 and SEZ seronegative Bama minipigs were immunized with rSPV-ICS (n=8), commercial PCV2 vaccine and SEZ vaccine (n=8) or wild type SPV (n=8). The results showed that SzP-specific antibody and PCV2 neutralizing antibody of the rSPV-ICS immunized group increased significantly compared to the wild type SPV treated group after vaccination and increased continuously over time. The levels of IL-4 and IFN-γ in the rSPV-ICS immunized group were significantly higher than the other three groups, respectively. After been co-challenged with PCV2 and SEZ, 87.5% piglets in rSPV-ICS immunized group were survived. Significant reductions in gross lung lesion score, histopathological lung lesion score, and lymph node lesion score were noticed in the rSPV-ICS immunized group compared with the wtSPV treated group. The results suggested that the recombinant rSPV-ICS provided piglets with significant protection against PCV2-SEZ co-infection; thus, it offers proof-of-principle for the development of a vaccine for the prevention of these swine diseases. Copyright © 2014 Elsevier B.V. All rights reserved.

Chromatin interaction networks revealed unique connectivity patterns of broad H3K4me3 domains and super enhancers in 3D chromatin.

PubMed

Thibodeau, Asa; Márquez, Eladio J; Shin, Dong-Guk; Vera-Licona, Paola; Ucar, Duygu

2017-10-31

Broad domain promoters and super enhancers are regulatory elements that govern cell-specific functions and harbor disease-associated sequence variants. These elements are characterized by distinct epigenomic profiles, such as expanded deposition of histone marks H3K27ac for super enhancers and H3K4me3 for broad domains, however little is known about how they interact with each other and the rest of the genome in three-dimensional chromatin space. Using network theory methods, we studied chromatin interactions between broad domains and super enhancers in three ENCODE cell lines (K562, MCF7, GM12878) obtained via ChIA-PET, Hi-C, and Hi-CHIP assays. In these networks, broad domains and super enhancers interact more frequently with each other compared to their typical counterparts. Network measures and graphlets revealed distinct connectivity patterns associated with these regulatory elements that are robust across cell types and alternative assays. Machine learning models showed that these connectivity patterns could effectively discriminate broad domains from typical promoters and super enhancers from typical enhancers. Finally, targets of broad domains in these networks were enriched in disease-causing SNPs of cognate cell types. Taken together these results suggest a robust and unique organization of the chromatin around broad domains and super enhancers: loci critical for pathologies and cell-specific functions.

Chromospheres of Coronal Stars

NASA Technical Reports Server (NTRS)

Linsky, Jeffrey L.; Wood, Brian E.

1996-01-01

We summarize the main results obtained from the analysis of ultraviolet emission line profiles of coronal late-type stars observed with the Goddard High Resolution Spectrograph (GHRS) on the Hubble Space Telescope. The excellent GHRS spectra provide new information on magnetohydrodynamic phenomena in the chromospheres and transition regions of these stars. One exciting new result is the discovery of broad components in the transition region lines of active stars that we believe provide evidence for microflare heating in these stars.

DNA-dependent protein kinase is a molecular target for the development of noncytotoxic radiation-sensitizing drugs.

PubMed

Shinohara, Eric T; Geng, Ling; Tan, Jiahui; Chen, Heidi; Shir, Yu; Edwards, Eric; Halbrook, James; Kesicki, Edward A; Kashishian, Adam; Hallahan, Dennis E

2005-06-15

DNA-dependent protein kinase (DNA-PK)-defective severe combined immunodeficient (SCID) mice have a greater sensitivity to ionizing radiation compared with wild-type mice due to deficient repair of DNA double-strand break. SCID cells were therefore studied to determine whether radiosensitization by the specific inhibitor of DNA-PK, IC87361, is eliminated in the absence of functional DNA-PK. IC87361 enhanced radiation sensitivity in wild-type C57BL6 endothelial cells but not in SCID cells. The tumor vascular window model was used to assess IC87361-induced radiosensitization of SCID and wild-type tumor microvasculature. Vascular density was 5% in irradiated SCID host compared with 50% in C57BL6 mice (P < 0.05). IC87361 induced radiosensitization of tumor microvasculature in wild-type mice that resembled the radiosensitive phenotype of tumor vessels in SCID mice. Radiosensitization by IC87361 was eliminated in SCID tumor vasculature, which lack functional DNA-PK. Irradiated LLC and B16F0 tumors implanted into SCID mice showed greater tumor growth delay compared with tumors implanted into either wild-type C57BL6 or nude mice. Furthermore, LLC tumors treated with radiation and IC87361 showed tumor growth delay that was significantly greater than tumors treated with radiation alone (P < 0.01 for 3 Gy alone versus 3 Gy + IC87361). DNA-PK inhibitors induced no cytotoxicity and no toxicity in mouse normal tissues. Mouse models deficient in enzyme activity are useful to assess the specificity of novel kinase inhibitors. DNA-PK is an important target for the development of novel radiation-sensitizing drugs that have little intrinsic cytotoxicity.

Selectivity of Pinus sylvestris extract and essential oil to estrogen-insensitive breast cancer cells Pinus sylvestris against cancer cells.

PubMed

Hoai, Nguyen Thi; Duc, Ho Viet; Thao, Do Thi; Orav, Anne; Raal, Ain

2015-10-01

So far, the anticancer action of pine tree extracts has mainly been shown for the species distributed widely around the Asian countries. Therefore, this study was performed to examine the potential cytotoxicity of Scots pine (Pinus sylvestris L.) native also to the European region and growing widely in Estonia. The cytotoxic activity of methanol extract and essential oil of Scots pine needles was determined by sulforhodamine B assay in different human cancer cell lines. This needle extract was found to suppress the viability of several human cancer cell lines showing some selectivity to estrogen receptor negative breast cancer cells, MDA-MB-231(half maximal inhibitory concentration [IC50] 35 μg/ml) in comparison with estrogen receptor-positive breast cancer cells, MCF-7 (IC50 86 μg/ml). It is the strongest cytotoxic effect at all measured, thus far for the needles and leaves extracts derived from various pine species, and is also the first study comparing the anticancer effects of pine tree extracts on molecularly different human breast cancer cells. The essential oil showed the stronger cytotoxic effect to both negative and positive breast cancer cell lines (both IC50 29 μg/ml) than pine extract (IC50 42 and 80 μg/ml, respectively). The data from this report indicate that Scots pine needles extract and essential oil exhibits some potential as chemopreventive or chemotherapeutic agent for mammary tumors unresponsive to endocrine treatment.

Triterpenoid saponins from the roots of Clematis argentilucida.

PubMed

Zhao, Mei; Ma, Ning; Qiu, Feng; Tian, Xiangrong; Zhang, Yan; Tang, Haifeng; Liu, Xinyou

2014-09-01

Reinvestigation of the n-BuOH extract of the roots of Clematis argentilucida led to the isolation of a new ursane-type triterpenoid saponin 1 and a new taraxerane-type saponin 2, four known saponins 3-6 first isolated from the species, together with seven saponins 7-13 reported in the previous papers. The structures of saponins 1-6 were elucidated by extensive spectroscopic analysis and chemical evidences. The ursane-type and taraxerane-type triterpenoid saponins were obtained from genus Clematis for the first time, and the aglycone of saponin 1, 3β,28-dihydroxy-18αH-ursan-20-en was first encountered. The cytotoxicity of all the saponins was evaluated against human glioblastoma U251MG cell lines. The monodesmosidic saponins 1, 2 and 4-8 exhibited cytotoxic activity against the cells with IC50 values ranging from 6.95 to 38.51 μM. Copyright © 2014 Elsevier B.V. All rights reserved.

CYT387, a selective JAK1/JAK2 inhibitor: in vitro assessment of kinase selectivity and preclinical studies using cell lines and primary cells from polycythemia vera patients.

PubMed

Pardanani, A; Lasho, T; Smith, G; Burns, C J; Fantino, E; Tefferi, A

2009-08-01

Somatic mutations in Janus kinase 2 (JAK2), including JAK2V617F, result in dysregulated JAK-signal transducer and activator transcription (STAT) signaling, which is implicated in myeloproliferative neoplasm (MPN) pathogenesis. CYT387 is an ATP-competitive small molecule that potently inhibits JAK1/JAK2 kinases (IC(50)=11 and 18 nM, respectively), with significantly less activity against other kinases, including JAK3 (IC(50)=155 nM). CYT387 inhibits growth of Ba/F3-JAK2V617F and human erythroleukemia (HEL) cells (IC(50) approximately 1500 nM) or Ba/F3-MPLW515L cells (IC(50)=200 nM), but has considerably less activity against BCR-ABL harboring K562 cells (IC=58 000 nM). Cell lines harboring mutated JAK2 alleles (CHRF-288-11 or Ba/F3-TEL-JAK2) were inhibited more potently than the corresponding pair harboring mutated JAK3 alleles (CMK or Ba/F3-TEL-JAK3), and STAT-5 phosphorylation was inhibited in HEL cells with an IC(50)=400 nM. Furthermore, CYT387 selectively suppressed the in vitro growth of erythroid colonies harboring JAK2V617F from polycythemia vera (PV) patients, an effect that was attenuated by exogenous erythropoietin. Overall, our data indicate that the JAK1/JAK2 selective inhibitor CYT387 has potential for efficacious treatment of MPN harboring mutated JAK2 and MPL alleles.

On Local Ionization Equilibrium and Disk Winds in QSOs

NASA Astrophysics Data System (ADS)

Pereyra, Nicolas A.

2014-11-01

We present theoretical C IV λλ1548,1550 absorption line profiles for QSOs calculated assuming the accretion disk wind (ADW) scenario. The results suggest that the multiple absorption troughs seen in many QSOs may be due to the discontinuities in the ion balance of the wind (caused by X-rays), rather than discontinuities in the density/velocity structure. The profiles are calculated from a 2.5-dimensional time-dependent hydrodynamic simulation of a line-driven disk wind for a typical QSO black hole mass, a typical QSO luminosity, and for a standard Shakura-Sunyaev disk. We include the effects of ionizing X-rays originating from within the inner disk radius by assuming that the wind is shielded from the X-rays from a certain viewing angle up to 90° ("edge on"). In the shielded region, we assume constant ionization equilibrium, and thus constant line-force parameters. In the non-shielded region, we assume that both the line-force and the C IV populations are nonexistent. The model can account for P-Cygni absorption troughs (produced at edge on viewing angles), multiple absorption troughs (produced at viewing angles close to the angle that separates the shielded region and the non-shielded region), and for detached absorption troughs (produced at an angle in between the first two absorption line types); that is, the model can account for the general types of broad absorption lines seen in QSOs as a viewing angle effect. The steady nature of ADWs, in turn, may account for the steady nature of the absorption structure observed in multiple-trough broad absorption line QSOs. The model parameters are M bh = 109 M ⊙ and L disk = 1047 erg s-1.

Two-Wire to Four-Wire Audio Converter

NASA Technical Reports Server (NTRS)

Talley, G. L., Jr; Seale, B. L.

1983-01-01

Simple circuit provides interface between normally incompatible voicecommunication lines. Circuit maintains 40 dB of isolation between input and output halves of four-wire line permitting two-wire line to be connected. Balancing potentiometer, Rg, adjusts gain of IC2 to null feed through from input to output. Adjustment is done on workbench just after assembly.

Multivalent dendrimeric compounds containing carbohydrates expressed on immune cells inhibit infection by primary isolates of HIV-1

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

Rosa Borges, Andrew; Wieczorek, Lindsay; Johnson, Benitra

2010-12-05

Specific glycosphingolipids (GSL), found on the surface of target immune cells, are recognized as alternate cell surface receptors by the human immunodeficiency virus type 1 (HIV-1) external envelope glycoprotein. In this study, the globotriose and 3'-sialyllactose carbohydrate head groups found on two GSL were covalently attached to a dendrimer core to produce two types of unique multivalent carbohydrates (MVC). These MVC inhibited HIV-1 infection of T cell lines and primary peripheral blood mononuclear cells (PBMC) by T cell line-adapted viruses or primary isolates, with IC{sub 50}s ranging from 0.1 to 7.4 {mu}g/ml. Inhibition of Env-mediated membrane fusion by MVC wasmore » also observed using a dye-transfer assay. These carbohydrate compounds warrant further investigation as a potential new class of HIV-1 entry inhibitors. The data presented also shed light on the role of carbohydrate moieties in HIV-1 virus-host cell interactions. -- Research Highlights: {yields}Multivalent carbohydrates (MVCs) inhibited infection of PBMCs by HIV-1. {yields}MVCs inhibited infection by T cell line-adapted viruses. {yields}MVCs inhibited infection by primary isolates of HIV-1. {yields}MVCs inhibited Env-mediated membrane fusion.« less

Global structure of mantle isotopic heterogeneity and its implications for mantle differentiation and convection

NASA Astrophysics Data System (ADS)

Iwamori, Hikaru; Albaréde, Francis; Nakamura, Hitomi

2010-11-01

In order to further our understanding of the global geochemical structure and mantle dynamics, a global isotopic data set of oceanic basalts was analyzed by Independent Component Analysis (ICA), a relatively new method of multivariate analysis. The data set consists of 2773 mid-ocean ridge basalts (MORB) and 1515 ocean island basalts (OIB) with five isotopic ratios of Pb, Nd and Sr. The data set spatially covers the major oceans and enables us to compare the results with global geophysical observations. Three independent components (ICs) have been found, two of which are essentially identical to those previously found for basalts from the Atlantic and Indian Oceans. The two ICs (IC1 and IC2) span a compositional plane that accounts for 95.7% of the sample variance, while the third IC (IC3) accounts for 3.7%. Based on the geochemical nature of ICs and a forward model concerning trace elemental and isotopic compositions, the origin of the ICs is discussed. IC1 discriminates OIB from MORB, and may be related to elemental fractionation associated with melting and the subsequent radiogenic in growth with an average recycling time of 0.8 to 2.4 Ga. IC2 tracks the regional provenance of both MORB and OIB and may be related to aqueous fluid-rock interaction and the subsequent radiogenic ingrowth with an average recycling time of 0.3 to 0.9 Ga. IC3 fingerprints upper continental crustal material and its high value appears in limited geographical and tectonic settings. Variations in the melt component (IC1) and in the aqueous fluid component (IC2) inherited in the mantle most likely reflect mid-ocean ridge and subduction zone processes, respectively. Long-term accumulation of dense materials rich in the IC1 melt component at the base of the convective mantle accounts for its longer recycling time with respect to that for less dense materials rich in the aqueous fluid component (IC2). IC2 broadly correlates with the seismic velocity structures of the lowermost mantle and electric conductivity around the mantle transition zones. We propose that IC2 reflects hydrogen distribution within the mantle and that several global domains enriched in hydrogen could exist as vertical sectors extending all the way down to the core-mantle boundary.

A review on high-resolution CMOS delay lines: towards sub-picosecond jitter performance.

PubMed

Abdulrazzaq, Bilal I; Abdul Halin, Izhal; Kawahito, Shoji; Sidek, Roslina M; Shafie, Suhaidi; Yunus, Nurul Amziah Md

2016-01-01

A review on CMOS delay lines with a focus on the most frequently used techniques for high-resolution delay step is presented. The primary types, specifications, delay circuits, and operating principles are presented. The delay circuits reported in this paper are used for delaying digital inputs and clock signals. The most common analog and digitally-controlled delay elements topologies are presented, focusing on the main delay-tuning strategies. IC variables, namely, process, supply voltage, temperature, and noise sources that affect delay resolution through timing jitter are discussed. The design specifications of these delay elements are also discussed and compared for the common delay line circuits. As a result, the main findings of this paper are highlighting and discussing the followings: the most efficient high-resolution delay line techniques, the trade-off challenge found between CMOS delay lines designed using either analog or digitally-controlled delay elements, the trade-off challenge between delay resolution and delay range and the proposed solutions for this challenge, and how CMOS technology scaling can affect the performance of CMOS delay lines. Moreover, the current trends and efforts used in order to generate output delayed signal with low jitter in the sub-picosecond range are presented.

Arabidopsis serotonin N-acetyltransferase knockout mutant plants exhibit decreased melatonin and salicylic acid levels resulting in susceptibility to an avirulent pathogen.

PubMed

Lee, Hyoung Yool; Byeon, Yeong; Tan, Dun-Xian; Reiter, Russel J; Back, Kyoungwhan

2015-04-01

Serotonin N-acetyltransferase (SNAT) is the penultimate enzyme in the melatonin biosynthesis pathway in plants. We examined the effects of SNAT gene inactivation in two Arabidopsis T-DNA insertion mutant lines. After inoculation with the avirulent pathogen Pseudomonas syringe pv. tomato DC3000 harboring the elicitor avrRpt2 (Pst-avrRpt2), melatonin levels in the snat knockout mutant lines were 50% less than in wild-type Arabidopsis Col-0 plants. The snat knockout mutant lines exhibited susceptibility to pathogen infection that coincided with decreased induction of defense genes including PR1, ICS1, and PDF1.2. Because melatonin acts upstream of salicylic acid (SA) synthesis, the reduced melatonin levels in the snat mutant lines led to decreased SA levels compared to wild-type, suggesting that the increased pathogen susceptibility of the snat mutant lines could be attributed to decreased SA levels and subsequent attenuation of defense gene induction. Exogenous melatonin treatment failed to induce defense gene expression in nahG Arabidopsis plants, but restored the induction of defense gene expression in the snat mutant lines. In addition, melatonin caused translocation of NPR1 (nonexpressor of PR1) protein from the cytoplasm into the nucleus indicating that melatonin-elicited pathogen resistance in response to avirulent pathogen attack is SA-dependent in Arabidopsis. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Solid-phase total synthesis of cherimolacyclopeptide E and discovery of more potent analogues by alanine screening.

PubMed

Shaheen, Farzana; Rizvi, Tania S; Musharraf, Syed G; Ganesan, A; Xiao, Kai; Townsend, Jared B; Lam, Kit S; Choudhary, M Iqbal

2012-11-26

Cherimolacyclopeptide E (1) is a cyclic hexapeptide obtained from Annona cherimola, reported to be cytotoxic against the KB (human nasopharyngeal carcinoma) cell line. The solid-phase total syntheses of this cyclic peptide and its analogues were accomplished by employing FMOC/tert-butyl-protected amino acids and the Kenner sulfonamide safety-catch linker. The synthetic peptide 1 was found to be weakly cytotoxic against four cell lines (MOLT-4, Jurkat T lymphoma, MDA-MB-231, and KB). Analogues 3 and 7, where glycine at positions 2 and 6 of the parent compound was replaced by Ala, exhibited enhanced cytotoxicity against KB (3, IC50 6.3 μM; 7, IC50 7.8 μM) and MDA-MB-231 breast cancer cells (3, IC50 10.2 μM; 7, IC50 7.7 μM), thereby suggesting possible selective targeting of these cancer cells by these peptides. The spectral data of synthetic peptide 1 was found to be similar to that reported for the natural product. However, a striking difference in biological activity was noted, which warrants the re-evaluation of the original natural product for purity and the existence of conformational differences.

Synthesis and biological evaluation of tricyclic guanidine analogues of batzelladine K for antimalarial, antileishmanial, antibacterial, antifungal, and anti-HIV activities.

PubMed

Ahmed, Nafees; Brahmbhatt, Keyur G; Khan, Shabana I; Jacob, Melissa; Tekwani, Babu L; Sabde, Sudeep; Mitra, Debashis; Singh, Inder P; Khan, Ikhlas A; Bhutani, Kamlesh K

2013-04-01

Fifty analogues of batzelladine K were synthesized and evaluated for in vitro antimalarial (Plasmodium falciparum), antileishmanial (Leishmania donovani), antimicrobial (panel of bacteria and fungi), antiviral (HIV-1) activities. Analogues 14h and 20l exhibited potential antimalarial activity against chloroquine-sensitive D6 strain with IC(50) 1.25 and 0.88 μM and chloroquine-resistant W2 strain with IC(50) 1.64 and 1.07 μM, respectively. Analogues 12c and 14c having nonyl substitution showed the most potent antileishmanial activity with IC(50) 2.39 and 2.78 μM and IC(90) 11.27 and 12.76 μM, respectively. Three analogues 12c, 14c, and 14i were the most active against various pathogenic bacteria and fungi with IC(50) < 3.02 μM and MIC/MBC/MFC <6 μM. Analogue 20l having pentyl and methyl substituents on tricycle showed promising activities against all pathogens. However, none was found active against HIV-1. Our study demonstrated that the tricyclic guanidine compounds provide new structural class for broad spectrum activity. © 2012 John Wiley & Sons A/S.

Synthesis and biological evaluation of tricyclic guanidine analogues of batzelladine K for antimalarial, antileishmanial, antibacterial, antifungal and anti-HIV activities.

PubMed

Ahmed, Nafees; Brahmbhatt, Keyur G; Khan, Shabana I; Jacob, Melissa; Tekwani, Babu L; Sabde, Sudeep; Mitra, Debashis; Singh, Inder Pal; Khan, Ikhlas A; Bhutani, Kamlesh K

2012-06-15

Fifty analogues of batzelladine K were synthesized and evaluated for in vitro antimalarial (Plasmodium falciparum), antileishmanial (Leishmania donovani), antimicrobial (panel of bacteria and fungi), antiviral (HIV-1) activities. Analogues 14h and 20l exhibited potential antimalarial activity against chloroquine-sensitive D6 strain with IC 50 1.25 and 0.88 μM and chloroquine-resistant W2 strain with IC 50 1.64 and 1.07 μM, respectively. Analogues 12c and 14c having nonyl substitution showed the most potent antileishmanial activity with IC 50 2.39 and 2.78 μM and IC 90 11.27 and 12.76 μM respectively. Three analogues 12c, 14c and 14i were the most active against various pathogenic bacteria and fungi with IC 50 <3.02 μM and MIC/MBC/MFC <6 μM. Analogue 20l having pentyl and methyl substituents on tricycle showed promising activities against all pathogens. However, none was found active against HIV-1. Our study demonstrated that the tricyclic guanidine compounds provide new structral class for broad spectrum activity. © 2012 John Wiley & Sons A/S. © 2012 John Wiley & Sons A/S.

"Negotiorum Gestio" in Family Medicine, Informed Consent Obtainment, and Disciplinary Responsibility.

PubMed

Birkeland, Søren

2016-01-01

Introduction. Negotiorum gestio (NG) denotes an action where a person well intendedly acts on behalf of another without obtaining the latter's prior consent. In broad terms, NG-like actions have played a considerable role in health care provision. In some settings, health care delivery with only little or presumed patients' consent has been the rule rather than the exception. However, bioethical principles regarding patient autonomy and obtainment of the patient's informed consent (IC) before intervention are now increasingly materialized in the law of many countries. Aim. To study legal consequences of NG in family medicine and IC handling options. Methods. Case law examination. Results. A disciplinary board case is described concerning a family doctor conducting unlawful NG by not coming up to legal IC requirements. Discussion and Conclusion. The practical and legal implications of IC and possible role of novel Shared Decision-Making approaches in coming up to regulation and bioethical demands are discussed. It is concluded that a doctor may run an unnecessary legal risk when conducting NG in decision-competent patients and furthermore it is suggested that novel Shared Decision-Making approaches could help in obtaining a rightful and practicable IC.

Inter-computer communication architecture for a mixed redundancy distributed system

NASA Technical Reports Server (NTRS)

Lala, Jaynarayan H.; Adams, Stuart J.

1987-01-01

The triply redundant intercomputer network for the Advanced Information Processing System (AIPS), an architecture developed to serve as the core avionics system for a broad range of aerospace vehicles, is discussed. The AIPS intercomputer network provides a high-speed, Byzantine-fault-resilient communication service between processing sites, even in the presence of arbitrary failures of simplex and duplex processing sites on the IC network. The IC network contention poll has evolved from the Laning Poll. An analysis of the failure modes and effects and a simulation of the AIPS contention poll, demonstrate the robustness of the system.

The Carnegie Supernova Project I. Analysis of stripped-envelope supernova light curves

NASA Astrophysics Data System (ADS)

Taddia, F.; Stritzinger, M. D.; Bersten, M.; Baron, E.; Burns, C.; Contreras, C.; Holmbo, S.; Hsiao, E. Y.; Morrell, N.; Phillips, M. M.; Sollerman, J.; Suntzeff, N. B.

2018-02-01

Stripped-envelope (SE) supernovae (SNe) include H-poor (Type IIb), H-free (Type Ib), and He-free (Type Ic) events thought to be associated with the deaths of massive stars. The exact nature of their progenitors is a matter of debate with several lines of evidence pointing towards intermediate mass (Minit< 20 M⊙) stars in binary systems, while in other cases they may be linked to single massive Wolf-Rayet stars. Here we present the analysis of the light curves of 34 SE SNe published by the Carnegie Supernova Project (CSP-I) that are unparalleled in terms of photometric accuracy and wavelength range. Light-curve parameters are estimated through the fits of an analytical function and trends are searched for among the resulting fit parameters. Detailed inspection of the dataset suggests a tentative correlation between the peak absolute B-band magnitude and Δm15(B), while the post maximum light curves reveals a correlation between the late-time linear slope and Δm15. Making use of the full set of optical and near-IR photometry, combined with robust host-galaxy extinction corrections, comprehensive bolometric light curves are constructed and compared to both analytic and hydrodynamical models. This analysis finds consistent results among the two different modeling techniques and from the hydrodynamical models we obtained ejecta masses of 1.1-6.2M⊙, 56Ni masses of 0.03-0.35M⊙, and explosion energies (excluding two SNe Ic-BL) of 0.25-3.0 × 1051 erg. Our analysis indicates that adopting κ = 0.07 cm2 g-1 as the mean opacity serves to be a suitable assumption when comparing Arnett-model results to those obtained from hydrodynamical calculations. We also find that adopting He I and O I line velocities to infer the expansion velocity in He-rich and He-poor SNe, respectively, provides ejecta masses relatively similar to those obtained by using the Fe II line velocities, although the use of Fe II as a diagnostic does imply higher explosion energies. The inferred range of ejecta masses are compatible with intermediate mass (MZAMS ≤ 20M⊙) progenitor stars in binary systems for the majority of SE SNe. Furthermore, our hydrodynamical modeling of the bolometric light curves suggests a significant fraction of the sample may have experienced significant mixing of 56Ni, particularly in the case of SNe Ic. Based on observations collected at Las Campanas Observatory.Bolometric light curve tables are only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (http://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/609/A136

77 FR 11186 - Request for Comments on a New Information Collection

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-24

... of Transportation's aviation economic, consumer protection, and civil rights requirements. Among... Consumer Protection Division Web page On-Line Aviation Complaint Form. Type of Request: Request for an OMB... broad authority under 49 U.S.C., Subtitle VII, to investigate and enforce consumer protection and civil...

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

Jencson, Jacob E.; Kasliwal, Mansi M.; Cao, Yi

SPitzer InfraRed Intensive Transients Survey—SPIRITS—is an ongoing survey of nearby galaxies searching for infrared (IR) transients with Spitzer /IRAC. We present the discovery and follow-up observations of one of our most luminous ( M {sub [4.5]} = −17.1 ± 0.4 mag, Vega) and reddest ([3.6] − [4.5] = 3.0 ± 0.2 mag) transients, SPIRITS 15c. The transient was detected in a dusty spiral arm of IC 2163 ( D ≈ 35.5 Mpc). Pre-discovery ground-based imaging revealed an associated, shorter-duration transient in the optical and near-IR (NIR). NIR spectroscopy showed a broad (≈8400 km s{sup −1}), double-peaked emission line of Hemore » i at 1.083 μ m, indicating an explosive origin. The NIR spectrum of SPIRITS 15c is similar to that of the Type IIb SN 2011dh at a phase of ≈200 days. Assuming an A {sub V} = 2.2 mag of extinction in SPIRITS 15c provides a good match between their optical light curves. The NIR light curves, however, show some minor discrepancies when compared with SN 2011dh, and the extreme [3.6]–[4.5] color has not been previously observed for any SN IIb. Another luminous ( M {sub 4.5} = −16.1 ± 0.4 mag) event, SPIRITS 14buu, was serendipitously discovered in the same galaxy. The source displays an optical plateau lasting ≳80 days, and we suggest a scenario similar to the low-luminosity Type IIP SN 2005cs obscured by A{sub V} ≈ 1.5 mag. Other classes of IR-luminous transients can likely be ruled out in both cases. If both events are indeed SNe, this may suggest that ≳18% of nearby core-collapse SNe are missed by currently operating optical surveys.« less

Hitomi observation of radio galaxy NGC 1275: The first X-ray microcalorimeter spectroscopy of Fe-Kα line emission from an active galactic nucleus

NASA Astrophysics Data System (ADS)

Hitomi Collaboration; Aharonian, Felix; Akamatsu, Hiroki; Akimoto, Fumie; Allen, Steven W.; Angelini, Lorella; Audard, Marc; Awaki, Hisamitsu; Axelsson, Magnus; Bamba, Aya; Bautz, Marshall W.; Blandford, Roger; Brenneman, Laura W.; Brown, Gregory V.; Bulbul, Esra; Cackett, Edward M.; Chernyakova, Maria; Chiao, Meng P.; Coppi, Paolo S.; Costantini, Elisa; de Plaa, Jelle; de Vries, Cor P.; den Herder, Jan-Willem; Done, Chris; Dotani, Tadayasu; Ebisawa, Ken; Eckart, Megan E.; Enoto, Teruaki; Ezoe, Yuichiro; Fabian, Andrew C.; Ferrigno, Carlo; Foster, Adam R.; Fujimoto, Ryuichi; Fukazawa, Yasushi; Furuzawa, Akihiro; Galeazzi, Massimiliano; Gallo, Luigi C.; Gandhi, Poshak; Giustini, Margherita; Goldwurm, Andrea; Gu, Liyi; Guainazzi, Matteo; Haba, Yoshito; Hagino, Kouichi; Hamaguchi, Kenji; Harrus, Ilana M.; Hatsukade, Isamu; Hayashi, Katsuhiro; Hayashi, Takayuki; Hayashida, Kiyoshi; Hiraga, Junko S.; Hornschemeier, Ann; Hoshino, Akio; Hughes, John P.; Ichinohe, Yuto; Iizuka, Ryo; Inoue, Hajime; Inoue, Yoshiyuki; Ishida, Manabu; Ishikawa, Kumi; Ishisaki, Yoshitaka; Iwai, Masachika; Kaastra, Jelle; Kallman, Tim; Kamae, Tsuneyoshi; Kataoka, Jun; Katsuda, Satoru; Kawai, Nobuyuki; Kelley, Richard L.; Kilbourne, Caroline A.; Kitaguchi, Takao; Kitamoto, Shunji; Kitayama, Tetsu; Kohmura, Takayoshi; Kokubun, Motohide; Koyama, Katsuji; Koyama, Shu; Kretschmar, Peter; Krimm, Hans A.; Kubota, Aya; Kunieda, Hideyo; Laurent, Philippe; Lee, Shiu-Hang; Leutenegger, Maurice A.; Limousin, Olivier O.; Loewenstein, Michael; Long, Knox S.; Lumb, David; Madejski, Greg; Maeda, Yoshitomo; Maier, Daniel; Makishima, Kazuo; Markevitch, Maxim; Matsumoto, Hironori; Matsushita, Kyoko; McCammon, Dan; McNamara, Brian R.; Mehdipour, Missagh; Miller, Eric D.; Miller, Jon M.; Mineshige, Shin; Mitsuda, Kazuhisa; Mitsuishi, Ikuyuki; Miyazawa, Takuya; Mizuno, Tsunefumi; Mori, Hideyuki; Mori, Koji; Mukai, Koji; Murakami, Hiroshi; Mushotzky, Richard F.; Nakagawa, Takao; Nakajima, Hiroshi; Nakamori, Takeshi; Nakashima, Shinya; Nakazawa, Kazuhiro; Nobukawa, Kumiko K.; Nobukawa, Masayoshi; Noda, Hirofumi; Odaka, Hirokazu; Ohashi, Takaya; Ohno, Masanori; Okajima, Takashi; Ota, Naomi; Ozaki, Masanobu; Paerels, Frits; Paltani, Stéphane; Petre, Robert; Pinto, Ciro; Porter, Frederick S.; Pottschmidt, Katja; Reynolds, Christopher S.; Safi-Harb, Samar; Saito, Shinya; Sakai, Kazuhiro; Sasaki, Toru; Sato, Goro; Sato, Kosuke; Sato, Rie; Sawada, Makoto; Schartel, Norbert; Serlemitsos, Peter J.; Seta, Hiromi; Shidatsu, Megumi; Simionescu, Aurora; Smith, Randall K.; Soong, Yang; Stawarz, Łukasz; Sugawara, Yasuharu; Sugita, Satoshi; Szymkowiak, Andrew; Tajima, Hiroyasu; Takahashi, Hiromitsu; Takahashi, Tadayuki; Takeda, Shin'ichiro; Takei, Yoh; Tamagawa, Toru; Tamura, Takayuki; Tanaka, Takaaki; Tanaka, Yasuo; Tanaka, Yasuyuki T.; Tashiro, Makoto S.; Tawara, Yuzuru; Terada, Yukikatsu; Terashima, Yuichi; Tombesi, Francesco; Tomida, Hiroshi; Tsuboi, Yohko; Tsujimoto, Masahiro; Tsunemi, Hiroshi; Tsuru, Takeshi Go; Uchida, Hiroyuki; Uchiyama, Hideki; Uchiyama, Yasunobu; Ueda, Shutaro; Ueda, Yoshihiro; Uno, Shin'ichiro; Urry, C. Megan; Ursino, Eugenio; Watanabe, Shin; Werner, Norbert; Wilkins, Dan R.; Williams, Brian J.; Yamada, Shinya; Yamaguchi, Hiroya; Yamaoka, Kazutaka; Yamasaki, Noriko Y.; Yamauchi, Makoto; Yamauchi, Shigeo; Yaqoob, Tahir; Yatsu, Yoichi; Yonetoku, Daisuke; Zhuravleva, Irina; Zoghbi, Abderahmen; Kawamuro, Taiki

2018-03-01

The origin of the narrow Fe-Kα fluorescence line at 6.4 keV from active galactic nuclei has long been under debate; some of the possible sites are the outer accretion disk, the broad line region, a molecular torus, or interstellar/intracluster media. In 2016 February-March, we performed the first X-ray microcalorimeter spectroscopy with the Soft X-ray Spectrometer (SXS) on board the Hitomi satellite of the Fanaroff-Riley type I radio galaxy NGC 1275 at the center of the Perseus cluster of galaxies. With the high-energy resolution of ˜5 eV at 6 keV achieved by Hitomi/SXS, we detected the Fe-Kα line with ˜5.4 σ significance. The velocity width is constrained to be 500-1600 km s-1 (FWHM for Gaussian models) at 90% confidence. The SXS also constrains the continuum level from the NGC 1275 nucleus up to ˜20 keV, giving an equivalent width of ˜20 eV for the 6.4 keV line. Because the velocity width is narrower than that of the broad Hα line of ˜2750 km s-1, we can exclude a large contribution to the line flux from the accretion disk and the broad line region. Furthermore, we performed pixel map analyses on the Hitomi/SXS data and image analyses on the Chandra archival data, and revealed that the Fe-Kα line comes from a region within ˜1.6 kpc of the NGC 1275 core, where an active galactic nucleus emission dominates, rather than that from intracluster media. Therefore, we suggest that the source of the Fe-Kα line from NGC 1275 is likely a low-covering-fraction molecular torus or a rotating molecular disk which probably extends from a parsec to hundreds of parsecs scale in the active galactic nucleus system.

The Search for Wolf-Rayet Stars in IC10

NASA Astrophysics Data System (ADS)

Tehrani, Katie; Crowther, Paul; Archer, Isabelle

2017-11-01

We present a deep imaging and spectroscopic survey of the Local Group starburst galaxy IC10 using Gemini North/GMOS to unveil the global Wolf-Rayet population. It has previously been suggested that for IC10 to follow the WC/WN versus metallicity dependence seen in other Local Group galaxies, a large WN population must remain undiscovered. Our search revealed 3 new WN stars, and 5 candidates awaiting confirmation, providing little evidence to support this claim. We also compute an updated nebular derived metallicity of log(O/H)+12=8.40 +/- 0.04 for the galaxy using the direct method. Inspection of IC10 WR average line luminosities show these stars are more similar to their LMC, rather than SMC counterparts.

The Fast Evolution of SN 2010bh Associated with XRF 100316D

NASA Technical Reports Server (NTRS)

Olivares E., F.; Greiner, J.; Schady, P.; Rau, A.; Klose, S.; Kruhler, T.; Afonso, P. M. J.; Updike, A. C.; Nardini, M.; Filgas, R.;

Consequences of hot gas in the broad line region of active galactic nuclei

NASA Technical Reports Server (NTRS)

Kallman, T.; Mushotzky, R.

1985-01-01

Models for hot gas in the broad line region of active galactic nuclei are discussed. The results of the two phase equilibrium models for confinement of broad line clouds by Compton heated gas are used to show that high luminosity quasars are expected to show Fe XXVI L alpha line absorption which will be observed with spectrometers such as those planned for the future X-ray spectroscopy experiments. Two phase equilibrium models also predict that the gas in the broad line clouds and the confining medium may be Compton thick. It is shown that the combined effects of Comptonization and photoabsorption can suppress both the broad emission lines and X-rays in the Einstein and HEAO-1 energy bands. The observed properties of such Compton thick active galaxies are expected to be similar to those of Seyfert 2 nuclei. The implications for polarization and variability are also discussed.

The Hubble Space Telescope Quasar Absorption Line Key Project: The Unusual Absorption-Line System in the Spectrum of PG 2302+029--Ejected or Intervening?

NASA Technical Reports Server (NTRS)

Jannuzi, B. T.; Hartig, G. F.; Kirhakos, S.; Sargent, W. L. W.; Turnshek, D. A.; Weymann, R. J.; Bahcall, J. N.; Bergeron, J.; Boksenberg, A.; Savage, B. D.;

Photoionization modelling of the giant broad-line region in NGC 3998

NASA Astrophysics Data System (ADS)

Devereux, Nick

2018-01-01

Prior high angular resolution spectroscopic observations of the Low-ionization nuclear emission-line region (Liner) in NGC 3998 obtained with the Space Telescope Imaging Spectrograph (STIS) aboard the Hubble Space Telescope (HST) revealed a rich UV-visible spectrum consisting of broad permitted and broad forbidden emission lines. The photoionization code XSTAR is employed together with reddening-insensitive emission line diagnostics to constrain a dynamical model for the broad-line region (BLR) in NGC 3998. The BLR is modelled as a large H+ region ∼ 7 pc in radius consisting of dust-free, low-density ∼ 104 cm-3, low-metallicity ∼ 0.01 Z/Z⊙ gas. Modelling the shape of the broad H α emission line significantly discriminates between two independent measures of the black hole (BH) mass, favouring the estimate of de Francesco, Capetti & Marconi (2006). Interpreting the broad H α emission line in terms of a steady-state spherically symmetric inflow leads to a mass inflow rate of 1.4 × 10-2 M⊙ yr-1, well within the present uncertainty of calculations that attempt to explain the observed X-ray emission in terms of an advection-dominated accretion flow (ADAF). Collectively, the model provides an explanation for the shape of the H α emission line, the relative intensities and luminosities for the H Balmer, [O III], and potentially several of the broad UV emission lines, as well as refining the initial conditions needed for future modelling of the ADAF.

Goddard High-Resolution Spectrograph Observations of Procyon and HR1099

NASA Technical Reports Server (NTRS)

Wood, Brian E.; Harper, Graham M.; Linsky, Jeffrey L.; Dempsey, Robert C.

1996-01-01

Goddard High Resolution Spectrograph (GHRS) observations have revealed the presence of broad wings in the transition-region lines of AU Mic and Capella. It has been proposed that these wings are signatures of microflares in the transition regions of these stars and that the solar analog for this phenomenon might be the 'transition region explosive events' discussed by Dere, Bartoe, & Brueckner. We have analyzed GHRS observations of Procyon (F5 IV-V) and HR 1099 (K1 IV + G5 IV) to search for broad wings in the UV emission lines of these stars. We find that the transition-region lines of HR 1099, which are emitted almost entirely by the K1 star, do indeed have broad wings that are even more prominent than those of AU Mic and Capella. This is consistent with the association of the broad wings with microflaring since HR 1099 is a very active binary system. In contrast, the transition-region lines of Procyon, a relatively inactive star, do not show evidence for broad wings, with the possible exception of N v lambda1239. However, Procyon's lines do appear to have excess emission in their blue wings. Linsky et al. found no evidence for broad wings in Capella's chromospheric lines, but we find that the Mg II resonance lines of HR 1099 do have broad wings. The striking resemblance between HR 1099's Mg II and C iv lines suggests that the Mg II line profiles may be regulated by turbulent processes similar to those that control the transition-region line profiles. If this is the case, microflaring may be occurring in the K1 star's chromosphere as well as in its transition region. However, radiative transfer calculations suggest that the broad wings of the Mg II lines can also result from normal chromospheric opacity effects rather than pure turbulence. The prominence of broad wings in the transition region and perhaps even chromospheric lines of active stars suggests that microflaring is very prevalent in the outer atmospheres of active stars.

Relativistic redshifts in quasar broad lines

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

Tremaine, Scott; Shen, Yue; Liu, Xin

2014-10-10

The broad emission lines commonly seen in quasar spectra have velocity widths of a few percent of the speed of light, so special- and general-relativistic effects have a significant influence on the line profile. We have determined the redshift of the broad Hβ line in the quasar rest frame (determined from the core component of the [O III] line) for over 20,000 quasars from the Sloan Digital Sky Survey Data Release 7 quasar catalog. The mean redshift as a function of line width is approximately consistent with the relativistic redshift that is expected if the line originates in a randomlymore » oriented Keplerian disk that is obscured when the inclination of the disk to the line of sight exceeds ∼30°-45°, consistent with simple active galactic nucleus unification schemes. This result also implies that the net line-of-sight inflow/outflow velocities in the broad-line region are much less than the Keplerian velocity when averaged over a large sample of quasars with a given line width.« less

No Compton Reflection In a Chandra/RXTE Observation of Mkn 509: Implications for the Fe-K Line Emission From Accreting X-Ray Sources

NASA Technical Reports Server (NTRS)

Yaqoob, Tahir; Padmanabhan, Urmila; Kraemer, Steven B.; Crenshaw, D. Michael; Mckernan, Barry; George, Ian M.; Turner, T. Jane; White, Nicholas E. (Technical Monitor)

2002-01-01

We report the results of simultaneous Chandra and RXTE observations of the Seyfert 1 galaxy Mkn 509. We deconvolve the broad and narrow Fe-K emission-line components for which we measure rest-frame equivalent widths of 119+/-18 eV and 57+/-13 eV respectively. The broad line has a FWHM of 57,600((sup 14,400)(sub -21,000)) km/s and the narrow line is unresolved, with an upper limit on the FWHM of 4,940 km/s. Both components must originate in cool matter since we measure rest-frame center energies of 6.36((sup +0.13)(sub -0.12)) keV and 6.42+/-0.01 keV for the broad and narrow line respectively. This rules out He-like and H-like Fe for the origin of both the broad and narrow lines. If, as is widely accepted, the broad Fe-K line originates in Thomson-thick matter (such as an accretion disk), then one expects to observe spectral curvature above approximately 10 keV, (commensurate with the observed broad line), characteristic of the Compton-reflection continuum. However our data sets very stringent limits on deviations of the observed continuum from a power law. Light travel-time delays cannot be invoked to explain anomalies in the relative strengths of the broad Ferry line and Compton-reflection continuum since they are supposed to originate in the same physical location. We are forced to conclude that both the broad and narrow Fe-K lines had to originate in Thomson-thin matter during our observation. This result, for a single observation of just one source, means that our understanding of Fe K line emission and Compton reflection from accreting X-ray sources in general needs to be re-examined. For example, if an irradiated accretion disk existed in Mkn 509 at the time of the observations, the lack of spectral curvature above approximately 10 keV suggests two possibilities. Either the disk was Thomson-thick and highly ionized, having negligible Fe-K line emission and photoelectric absorption or the disk was Thomson-thin producing some or all of the broad Fe-K line emission. In the former case, the broad Fe-K line had to have produced in a Thomson-thin region elsewhere. In both cases the predicted spectral curvature above approximately 10 keV is negligible. An additional implication of our results is that any putative obscuring torus in the system, required by unification models of active galaxies, must also be Thomson-thin. The same applies to the optical broad line region (BLR) if it has a substantial covering factor.

Abundances of Neutral and Ionized PAH Along The Lines-of-Sight of Diffuse and Translucent Interstellar Clouds

NASA Technical Reports Server (NTRS)

Salama, Farid; Galazutdinov, Gazinur; Krewloski, Jacek; Biennier, Ludovic; Beletsky, Yuri; Song, In-Ok

2013-01-01

The spectra of neutral and ionized PAHs isolated in the gas phase at low temperature have been measured in the laboratory under conditions that mimic interstellar conditions and are compared with a set of astronomical spectra of reddened, early type stars. The comparisons of astronomical and laboratory data provide upper limits for the abundances of neutral PAH molecules and ions along specific lines-of-sight. Something that is not attainable from infrared observations. We present the characteristics of the laboratory facility (COSmIC) that was developed for this study and discuss the findings resulting from the comparison of the laboratory data with high resolution, high S/N ratio astronomical observations. COSmIC combines a supersonic jet expansion with discharge plasma and cavity ringdown spectroscopy and provides experimental conditions that closely mimic the interstellar conditions. The column densities of the individual PAH molecules and ions probed in these surveys are derived from the comparison of the laboratory data with high resolution, high S/N ratio astronomical observations. The comparisons of astronomical and laboratory data lead to clear conclusions regarding the expected abundances for PAHs in the interstellar environments probed in the surveys. Band profile comparisons between laboratory and astronomical spectra lead to information regarding the molecular structures and characteristics associated with the DIB carriers in the corresponding lines-of-sight. These quantitative surveys of neutral and ionized PAHs in the optical range open the way for quantitative searches of PAHs and complex organics in a variety of interstellar and circumstellar environments.

VizieR Online Data Catalog: X-Ray source properties for NGC 2207/IC 2163 (Mineo+, 2014)

NASA Astrophysics Data System (ADS)

Mineo, S.; Rappaport, S.; Levine, A.; Pooley, D.; Steinhorn, B.; Homan, J.

2017-08-01

We analyzed four Chandra ACIS-S observations of the galaxy pair NGC 2207/IC 2163. The data reduction was done following the standard CIAO threads (CIAO version 4.6, CALDB version 4.5.9) for soft (0.5-2 keV), hard (2-8 keV), and broad (0.5-8.0 keV) energy bands. All Chandra data sets were reprocessed using chandra_repro, a script that automates the recommended data-processing steps presented in the CIAO analysis threads. Using the script fluximage, we computed a monochromatic exposure map for the mean photon energy of each band: 1.25 keV, 5.0 keV, and 4.25 keV for the soft, hard, and broad band, respectively. fluximage outputs both the instrument map for the center of each energy band using the tool mkinstmap and the exposure maps in sky coordinates for each energy band using mkexpmap. (5 data files).

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

Cottaar, Michiel; Meyer, Michael R.; Covey, Kevin R.

Most field stars will have encountered the highest stellar density and hence the largest number of interactions in their birth environment. Yet the stellar dynamics during this crucial phase are poorly understood. Here we analyze the radial velocities measured for 152 out of 380 observed stars in the 2–6 Myr old star cluster IC 348 as part of the SDSS-III APOGEE. The radial velocity distribution of these stars is fitted with one or two Gaussians, convolved with the measurement uncertainties including binary orbital motions. Including a second Gaussian improves the fit; the high-velocity outliers that are best fit by thismore » second component may either (1) be contaminants from the nearby Perseus OB2 association, (2) be a halo of ejected or dispersing stars from IC 348, or (3) reflect that IC 348 has not relaxed to a Gaussian velocity distribution. We measure a velocity dispersion for IC 348 of 0.72 ± 0.07 km s{sup −1} (or 0.64 ± 0.08 km s{sup −1} if two Gaussians are fitted), which implies a supervirial state, unless the gas contributes more to the gravitational potential than expected. No evidence is found for a dependence of this velocity dispersion on distance from the cluster center or stellar mass. We also find that stars with lower extinction (in the front of the cloud) tend to be redshifted compared with stars with somewhat higher extinction (toward the back of the cloud). This data suggest that the stars in IC 348 are converging along the line of sight. We show that this correlation between radial velocity and extinction is unlikely to be spuriously caused by the small cluster rotation of 0.024 ± 0.013 km s{sup −1} arcmin{sup −1} or by correlations between the radial velocities of neighboring stars. This signature, if confirmed, will be the first detection of line of sight convergence in a star cluster. Possible scenarios for reconciling this convergence with IC 348's observed supervirial state include: (a) the cluster is fluctuating around a new virial equilibrium after a recent disruption due to gas expulsion or a merger event, or (b) the population we identify as IC 348 results from the chance alignment of two sub-clusters converging along the line of sight. Additional measurements of tangential and radial velocities in IC 348 will be important for clarifying the dynamics of this region and informing models of the formation and evolution of star clusters. The radial velocities analyzed in this paper have been made available online.« less

Long interspersed element-1 protein expression is a hallmark of many human cancers.

PubMed

Rodić, Nemanja; Sharma, Reema; Sharma, Rajni; Zampella, John; Dai, Lixin; Taylor, Martin S; Hruban, Ralph H; Iacobuzio-Donahue, Christine A; Maitra, Anirban; Torbenson, Michael S; Goggins, Michael; Shih, Ie-Ming; Duffield, Amy S; Montgomery, Elizabeth A; Gabrielson, Edward; Netto, George J; Lotan, Tamara L; De Marzo, Angelo M; Westra, William; Binder, Zev A; Orr, Brent A; Gallia, Gary L; Eberhart, Charles G; Boeke, Jef D; Harris, Chris R; Burns, Kathleen H

2014-05-01

Cancers comprise a heterogeneous group of human diseases. Unifying characteristics include unchecked abilities of tumor cells to proliferate and spread anatomically, and the presence of clonal advantageous genetic changes. However, universal and highly specific tumor markers are unknown. Herein, we report widespread long interspersed element-1 (LINE-1) repeat expression in human cancers. We show that nearly half of all human cancers are immunoreactive for a LINE-1-encoded protein. LINE-1 protein expression is a common feature of many types of high-grade malignant cancers, is rarely detected in early stages of tumorigenesis, and is absent from normal somatic tissues. Studies have shown that LINE-1 contributes to genetic changes in cancers, with somatic LINE-1 insertions seen in selected types of human cancers, particularly colon cancer. We sought to correlate this observation with expression of the LINE-1-encoded protein, open reading frame 1 protein, and found that LINE-1 open reading frame 1 protein is a surprisingly broad, yet highly tumor-specific, antigen. Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

IN-SYNC. III. The Dynamical State of IC 348 - A Super-virial Velocity Dispersion and a Puzzling Sign of Convergence

NASA Astrophysics Data System (ADS)

Cottaar, Michiel; Covey, Kevin R.; Foster, Jonathan B.; Meyer, Michael R.; Tan, Jonathan C.; Nidever, David L.; Chojnowski, S. Drew; da Rio, Nicola; Flaherty, Kevin M.; Frinchaboy, Peter M.; Majewski, Steve; Skrutskie, Michael F.; Wilson, John C.; Zasowski, Gail

2015-07-01

Most field stars will have encountered the highest stellar density and hence the largest number of interactions in their birth environment. Yet the stellar dynamics during this crucial phase are poorly understood. Here we analyze the radial velocities measured for 152 out of 380 observed stars in the 2-6 Myr old star cluster IC 348 as part of the SDSS-III APOGEE. The radial velocity distribution of these stars is fitted with one or two Gaussians, convolved with the measurement uncertainties including binary orbital motions. Including a second Gaussian improves the fit; the high-velocity outliers that are best fit by this second component may either (1) be contaminants from the nearby Perseus OB2 association, (2) be a halo of ejected or dispersing stars from IC 348, or (3) reflect that IC 348 has not relaxed to a Gaussian velocity distribution. We measure a velocity dispersion for IC 348 of 0.72 ± 0.07 km s-1 (or 0.64 ± 0.08 km s-1 if two Gaussians are fitted), which implies a supervirial state, unless the gas contributes more to the gravitational potential than expected. No evidence is found for a dependence of this velocity dispersion on distance from the cluster center or stellar mass. We also find that stars with lower extinction (in the front of the cloud) tend to be redshifted compared with stars with somewhat higher extinction (toward the back of the cloud). This data suggest that the stars in IC 348 are converging along the line of sight. We show that this correlation between radial velocity and extinction is unlikely to be spuriously caused by the small cluster rotation of 0.024 ± 0.013 km s-1 arcmin-1 or by correlations between the radial velocities of neighboring stars. This signature, if confirmed, will be the first detection of line of sight convergence in a star cluster. Possible scenarios for reconciling this convergence with IC 348's observed supervirial state include: (a) the cluster is fluctuating around a new virial equilibrium after a recent disruption due to gas expulsion or a merger event, or (b) the population we identify as IC 348 results from the chance alignment of two sub-clusters converging along the line of sight. Additional measurements of tangential and radial velocities in IC 348 will be important for clarifying the dynamics of this region and informing models of the formation and evolution of star clusters. The radial velocities analyzed in this paper have been made available online.

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

Ge Junqiang; Hu Chen; Wang Jianmin

Recently, much attention has been paid to double-peaked narrow emission-line (NEL) galaxies, some of which are suggested to be related to merging galaxies. We make a systematic search to build the largest sample of these sources from Data Release 7 of the Sloan Digital Sky Survey (SDSS). With reasonable criteria for fluxes, FWHMs of the emission lines, and separations of the peaks, we select 3030 double-peaked NEL galaxies. In light of the existence of broad Balmer lines and the locations of the two components of double-peaked NELs distinguished by the Kauffmann et al. criteria in the Baldwin-Phillips-Terlevich diagram, we findmore » that there are 81 Type I active galactic nuclei (AGNs), 837 double Type II AGNs (2-Type II), 708 galaxies with double star-forming components (2-SF), 400 with mixed star-forming and Type II AGN components (Type II + SF), and 1004 unknown-type objects. As a by-product, a sample of galaxies (12,582) with asymmetric or top-flat profiles of emission lines is established. After visually inspecting the SDSS images of the two samples, we find 54 galaxies with dual cores. The present samples can be used to study the dynamics of merging galaxies, the triggering mechanism of black hole activity, the hierarchical growth of galaxies, and the dynamics of narrow line regions driven by outflows and a rotating disk.« less

FLARE-LIKE VARIABILITY OF THE Mg II {lambda}2800 EMISSION LINE IN THE {gamma}-RAY BLAZAR 3C 454.3

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

Leon-Tavares, J.; Chavushyan, V.; Patino-Alvarez, V.

2013-02-01

We report the detection of a statistically significant flare-like event in the Mg II {lambda}2800 emission line of 3C 454.3 during the outburst of autumn 2010. The highest levels of emission line flux recorded over the monitoring period (2008-2011) coincide with a superluminal jet component traversing through the radio core. This finding crucially links the broad emission line fluctuations to the non-thermal continuum emission produced by relativistically moving material in the jet and hence to the presence of broad-line region clouds surrounding the radio core. If the radio core were located at several parsecs from the central black hole, thenmore » our results would suggest the presence of broad-line region material outside the inner parsec where the canonical broad-line region is envisaged to be located. We briefly discuss the implications of broad emission line material ionized by non-thermal continuum in the context of virial black hole mass estimates and gamma-ray production mechanisms.« less

A Census of Broad-line Active Galactic Nuclei in Nearby Galaxies: Coeval Star Formation and Rapid Black Hole Growth

NASA Astrophysics Data System (ADS)

Trump, Jonathan R.; Hsu, Alexander D.; Fang, Jerome J.; Faber, S. M.; Koo, David C.; Kocevski, Dale D.

2013-02-01

We present the first quantified, statistical map of broad-line active galactic nucleus (AGN) frequency with host galaxy color and stellar mass in nearby (0.01 < z < 0.11) galaxies. Aperture photometry and z-band concentration measurements from the Sloan Digital Sky Survey are used to disentangle AGN and galaxy emission, resulting in estimates of uncontaminated galaxy rest-frame color, luminosity, and stellar mass. Broad-line AGNs are distributed throughout the blue cloud and green valley at a given stellar mass, and are much rarer in quiescent (red sequence) galaxies. This is in contrast to the published host galaxy properties of weaker narrow-line AGNs, indicating that broad-line AGNs occur during a different phase in galaxy evolution. More luminous broad-line AGNs have bluer host galaxies, even at fixed mass, suggesting that the same processes that fuel nuclear activity also efficiently form stars. The data favor processes that simultaneously fuel both star formation activity and rapid supermassive black hole accretion. If AGNs cause feedback on their host galaxies in the nearby universe, the evidence of galaxy-wide quenching must be delayed until after the broad-line AGN phase.

Lucidumol C, a new cytotoxic lanostanoid triterpene from Ganoderma lingzhi against human cancer cells.

PubMed

Amen, Yhiya M; Zhu, Qinchang; Tran, Hai-Bang; Afifi, Mohamed S; Halim, Ahmed F; Ashour, Ahmed; Mira, Amira; Shimizu, Kuniyoshi

2016-07-01

A new oxygenated lanostane-type triterpene, named lucidumol C, together with six known compounds, was isolated from the chloroform extract of the fruiting bodies of Ganoderma lingzhi. Structures were established based on extensive spectroscopic and chemical studies. Potential cytotoxic activities of the isolated compounds were evaluated against human colorectal carcinoma (HCT-116, Caco-2), human liver carcinoma (HepG2), and human cervical carcinoma (HeLa) cell lines using WST-1 reagent. Selectivity was evaluated using normal human fibroblast cells (TIG-1 and HF19). Among the compounds, lucidumol C showed potent selective cytotoxicity against HCT-116 cells with an IC50 value of 7.86 ± 4.56 µM and selectivity index (SI) >10 with remarkable cytotoxic activities against Caco-2, HepG2 and HeLa cell lines.

Rearranged diterpenoids from the biotransformation of ent-trachyloban-18-oic acid by Rhizopus arrhizus.

PubMed

Leverrier, Aurélie; Martin, Marie-Thérèse; Servy, Claudine; Ouazzani, Jamal; Retailleau, Pascal; Awang, Khalijah; Mukhtar, Mat Ropi; Guéritte, Françoise; Litaudon, Marc

2010-06-25

In our search for inhibitors of the antiapoptotic protein Bcl-xL, investigation of Xylopia caudata afforded a new diterpenoid, ent-trachyloban-4beta-ol (2), and five known ent-trachylobane or ent-atisane compounds. Only ent-trachyloban-18-oic acid (1) exhibited weak binding activity to Bcl-xL. These compounds exhibited cytotoxicity against KB and HCT-116 cell lines with IC(50) values between 10 and 30 microM. Bioconversion of compound 1 by Rhizopus arrhizus afforded new hydroxylated metabolites (3-7) of the ent-trachylobane and ent-kaurene type and compound 8, with a rearranged pentacyclic carbon framework that was named rhizopene. Compounds 3-8 were noncytotoxic to the two cancer cell lines, and compounds 3 and 5 exhibited only weak binding affinity for Bcl-xL.

Six New neo-Clerodane Diterpenoids from Aerial Parts of Scutellaria barbata and Their Cytotoxic Activities.

PubMed

Yang, Guo-Chun; Hu, Jia-Hui; Li, Bing-Long; Liu, Huan; Wang, Jia-Yue; Sun, Li-Xin

2018-06-20

Six new neo-clerodane diterpenoids (1: -6: ), scutebatas X - Z, A 1 -C 1 , along with twelve known ones (7: -18: ) were obtained via the phytochemical investigation of the aerial parts of Scutellaria barbata . Their structures were established by detailed spectroscopic analysis. The absolute configurations of 1: and 2: , as the representative members of this type, were identified based on a circular dichroic exciton chirality method. Moreover, in vitro cytotoxicity of compounds 1: -6: were evaluated against three human cancer cell lines (SGC-7901, MCF-7, and A-549) using the MTT method. Compound 6: showed cytotoxic activities against all the three cell lines with IC 50 values of 17.9, 29.9, and 35.7 µM, respectively. Georg Thieme Verlag KG Stuttgart · New York.

Fucoidan cytotoxicity against human breast cancer T47D cell line increases with higher level of sulfate ester group

NASA Astrophysics Data System (ADS)

Saepudin, Endang; Alfita Qosthalani, Fildzah; Sinurat, Ellya

2018-01-01

The anticancer activity of different sulfate ester group content in different molecular weight was examined. The anticancer activity was achieved in vitro on human breast cancer T47D cell line. Fucoidan with lower molecular weight (5.79 kDa) tends to have lower sulfate ester group content (8.69%) and resulted in higher IC50 value (184.22 μg/mL). While fucoidan with higher molecular weight (785.12 kDa) tends to have higher sulfate level (18.63%) and achieved lower IC50 value (75.69 μg/mL). The result showed that in order to maintain fucoidan cytotoxic activity against human breast cancer T47D cell line, the sulfate content should be remain high. Keywords: fucoidan, sulfate ester group, human breast cancer

The Needle in the 100 deg2 Haystack: Uncovering Afterglows of Fermi GRBs with the Palomar Transient Factory

NASA Astrophysics Data System (ADS)

Singer, Leo P.; Kasliwal, Mansi M.; Cenko, S. Bradley; Perley, Daniel A.; Anderson, Gemma E.; Anupama, G. C.; Arcavi, Iair; Bhalerao, Varun; Bue, Brian D.; Cao, Yi; Connaughton, Valerie; Corsi, Alessandra; Cucchiara, Antonino; Fender, Rob P.; Fox, Derek B.; Gehrels, Neil; Goldstein, Adam; Gorosabel, J.; Horesh, Assaf; Hurley, Kevin; Johansson, Joel; Kann, D. A.; Kouveliotou, Chryssa; Huang, Kuiyun; Kulkarni, S. R.; Masci, Frank; Nugent, Peter; Rau, Arne; Rebbapragada, Umaa D.; Staley, Tim D.; Svinkin, Dmitry; Thöne, C. C.; de Ugarte Postigo, A.; Urata, Yuji; Weinstein, Alan

2015-06-01

The Fermi Gamma-ray Space Telescope has greatly expanded the number and energy window of observations of gamma-ray bursts (GRBs). However, the coarse localizations of tens to a hundred square degrees provided by the Fermi GRB Monitor instrument have posed a formidable obstacle to locating the bursts’ host galaxies, measuring their redshifts, and tracking their panchromatic afterglows. We have built a target-of-opportunity mode for the intermediate Palomar Transient Factory in order to perform targeted searches for Fermi afterglows. Here, we present the results of one year of this program: 8 afterglow discoveries out of 35 searches. Two of the bursts with detected afterglows (GRBs 130702A and 140606B) were at low redshift (z = 0.145 and 0.384, respectively) and had spectroscopically confirmed broad-line Type Ic supernovae. We present our broadband follow-up including spectroscopy as well as X-ray, UV, optical, millimeter, and radio observations. We study possible selection effects in the context of the total Fermi and Swift GRB samples. We identify one new outlier on the Amati relation. We find that two bursts are consistent with a mildly relativistic shock breaking out from the progenitor star rather than the ultra-relativistic internal shock mechanism that powers standard cosmological bursts. Finally, in the context of the Zwicky Transient Facility, we discuss how we will continue to expand this effort to find optical counterparts of binary neutron star mergers that may soon be detected by Advanced LIGO and Virgo.

The nature of the late B-type stars HD 67044 and HD 42035

NASA Astrophysics Data System (ADS)

Monier, R.; Gebran, M.; Royer, F.

2016-04-01

While monitoring a sample of apparently slowly rotating superficially normal bright late B and early A stars in the northern hemisphere, we have discovered that HD 67044 and HD 42035, hitherto classified as normal late B-type stars, are actually respectively a new chemically peculiar star and a new spectroscopic binary containing a very slow rotator HD 42035 S with ultra-sharp lines (v_{{e}}sin i= 3.7 km s^{-1}) and a fast rotator HD 42035 B with broad lines. The lines of Ti ii, Cr ii, Mn ii, Sr ii, Y ii, Zr ii and Ba ii are conspicuous features in the high resolution SOPHIE spectrum (R=75000) of HD 67044. The Hg ii line at 3983.93 Å is also present as a weak feature. The composite spectrum of HD 42035 is characterised by very sharp lines formed in HD 42035 S superimposed onto the shallow and broad lines of HD 42035 B. These very sharp lines are mostly due to light elements from C to Ni, the only heavy species definitely present are strontium and barium. Selected lines of 21 chemical elements from He up to Hg have been synthesized using model atmospheres computed with ATLAS9 and the spectrum synthesis code SYNSPEC48 including hyperfine structure of various isotopes when relevant. These synthetic spectra have been adjusted to high resolution high signal-to-noise spectra of HD 67044 and HD 42035 S in order to derive abundances of these key elements. HD 67044 is found to have distinct enhancements of Ti, Cr, Mn, Sr, Y, Zr, Ba and Hg and underabundances in He, C, O, Ca and Sc which shows that this star is not a superficially normal late B-type star, but actually is a new CP star most likely of the HgMn type. HD 42035 S has provisional underabundances of the light elements from C to Ti and overabundances of heavier elements (except for Fe and Sr which are also underabundant) up to barium. These values are lower limits to the actual abundances as we cannot currently place properly the continuum of HD 42035 S. More accurate fundamental parameters and abundances for HD 42035 S and HD 42035 B will be derived if we manage to disentangle their spectra. They will help clarify the status of the two components in this interesting new spectroscopic binary.

Constraints on the outer radius of the broad emission line region of active galactic nuclei

NASA Astrophysics Data System (ADS)

Landt, Hermine; Ward, Martin J.; Elvis, Martin; Karovska, Margarita

2014-03-01

Here we present observational evidence that the broad emission line region (BELR) of active galactic nuclei (AGN) generally has an outer boundary. This was already clear for sources with an obvious transition between the broad and narrow components of their emission lines. We show that the narrow component of the higher-order Paschen lines is absent in all sources, revealing a broad emission line profile with a broad, flat top. This indicates that the BELR is kinematically separate from the narrow emission line region. We use the virial theorem to estimate the BELR outer radius from the flat top width of the unblended profiles of the strongest Paschen lines, Paα and Paβ, and find that it scales with the ionizing continuum luminosity roughly as expected from photoionization theory. The value of the incident continuum photon flux resulting from this relationship corresponds to that required for dust sublimation. A flat-topped broad emission line profile is produced by both a spherical gas distribution in orbital motion and an accretion disc wind if the ratio between the BELR outer and inner radius is assumed to be less than ˜100-200. On the other hand, a pure Keplerian disc can be largely excluded, since for most orientations and radial extents of the disc the emission line profile is double-horned.

Cytotoxic and HIV-1 enzyme inhibitory activities of Red Sea marine organisms.

PubMed

Ellithey, Mona S; Lall, Namrita; Hussein, Ahmed A; Meyer, Debra

2014-02-25

Cancer and HIV/AIDS are two of the greatest public health and humanitarian challenges facing the world today. Infection with HIV not only weakens the immune system leading to AIDS and increasing the risk of opportunistic infections, but also increases the risk of several types of cancer. The enormous biodiversity of marine habitats is mirrored by the molecular diversity of secondary metabolites found in marine animals, plants and microbes which is why this work was designed to assess the anti-HIV and cytotoxic activities of some marine organisms of the Red Sea. The lipophilic fractions of methanolic extracts of thirteen marine organisms collected from the Red Sea (Egypt) were screened for cytotoxicity against two human cancer cell lines; leukaemia (U937) and cervical cancer (HeLa) cells. African green monkey kidney cells (Vero) were used as normal non-malignant control cells. The extracts were also tested for their inhibitory activity against HIV-1 enzymes, reverse transcriptase (RT) and protease (PR). Cytotoxicity results showed strong activity of the Cnidarian Litophyton arboreum against U-937 (IC50; 6.5 μg/ml ±2.3) with a selectivity index (SI) of 6.45, while the Cnidarian Sarcophyton trochliophorum showed strong activity against HeLa cells (IC50; 5.2 μg/ml ±1.2) with an SI of 2.09. Other species showed moderate to weak cytotoxicity against both cell lines. Two extracts showed potent inhibitory activity against HIV-1 protease; these were the Cnidarian jelly fish Cassiopia andromeda (IC50; 0.84 μg/ml ±0.05) and the red algae Galaxura filamentosa (2.6 μg/ml ±1.29). It is interesting to note that the most active extracts against HIV-1 PR, C. andromeda and G. filamentosa showed no cytotoxicity in the three cell lines at the highest concentration tested (100 μg/ml). The strong cytotoxicity of the soft corals L. arboreum and S. trochliophorum as well as the anti-PR activity of the jelly fish C. andromeda and the red algae G. filamentosa suggests the medicinal potential of crude extracts of these marine organisms.

Cytotoxic and HIV-1 enzyme inhibitory activities of Red Sea marine organisms

PubMed Central

2014-01-01

Background Cancer and HIV/AIDS are two of the greatest public health and humanitarian challenges facing the world today. Infection with HIV not only weakens the immune system leading to AIDS and increasing the risk of opportunistic infections, but also increases the risk of several types of cancer. The enormous biodiversity of marine habitats is mirrored by the molecular diversity of secondary metabolites found in marine animals, plants and microbes which is why this work was designed to assess the anti-HIV and cytotoxic activities of some marine organisms of the Red Sea. Methods The lipophilic fractions of methanolic extracts of thirteen marine organisms collected from the Red Sea (Egypt) were screened for cytotoxicity against two human cancer cell lines; leukaemia (U937) and cervical cancer (HeLa) cells. African green monkey kidney cells (Vero) were used as normal non-malignant control cells. The extracts were also tested for their inhibitory activity against HIV-1 enzymes, reverse transcriptase (RT) and protease (PR). Results Cytotoxicity results showed strong activity of the Cnidarian Litophyton arboreum against U-937 (IC50; 6.5 μg/ml ±2.3) with a selectivity index (SI) of 6.45, while the Cnidarian Sarcophyton trochliophorum showed strong activity against HeLa cells (IC50; 5.2 μg/ml ±1.2) with an SI of 2.09. Other species showed moderate to weak cytotoxicity against both cell lines. Two extracts showed potent inhibitory activity against HIV-1 protease; these were the Cnidarian jelly fish Cassiopia andromeda (IC50; 0.84 μg/ml ±0.05) and the red algae Galaxura filamentosa (2.6 μg/ml ±1.29). It is interesting to note that the most active extracts against HIV-1 PR, C. andromeda and G. filamentosa showed no cytotoxicity in the three cell lines at the highest concentration tested (100 μg/ml). Conclusion The strong cytotoxicity of the soft corals L. arboreum and S. trochliophorum as well as the anti-PR activity of the jelly fish C. andromeda and the red algae G. filamentosa suggests the medicinal potential of crude extracts of these marine organisms. PMID:24568567

Cytotoxicity and genotoxicity of coronaridine from Tabernaemontana catharinensis A.DC in a human laryngeal epithelial carcinoma cell line (Hep-2)

PubMed Central

Rizo, Walace Fraga; Ferreira, Luis Eduardo; Colnaghi, Vanessa; Martins, Juliana Simões; Franchi, Leonardo Pereira; Takahashi, Catarina Satie; Beleboni, Rene Oliveira; Marins, Mozart; Pereira, Paulo Sérgio; Fachin, Ana Lúcia

2013-01-01

Cancer has become a major public health problem worldwide and the number of deaths due to this disease is increasing almost exponentially. In the constant search for new treatments, natural products of plant origin have provided a variety of new compounds to be explored as antitumor agents. Tabernaemontana catharinensis is a medicinal plant that produces alkaloids with expressive antitumor activity, such as heyneanine, coronaridine and voacangine. The aim of present study was firstly to screen the cytotoxic activity of the indole alkaloids heyneanine, coronaridine and voacangine against HeLa (human cervix tumor), 3T3 (normal mouse embryo fibroblasts), Hep-2 (human laryngeal epithelial carcinoma) and B-16 (murine skin) cell lines by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide); and secondly to analyze the apoptotic activity, cell membrane damage and genotoxicity of the compound that showed the best cytotoxic activity against the tumor cell lines tested. Coronaridine was the one that exhibited greater cytotoxic activity in the laryngeal carcinoma cell line Hep-2 (IC50 = 54.47 μg/mL) than the other alkaloids tested (voacangine IC50 = 159.33 g/mL, and heyneanine IC50 = 689.45 μg/mL). Coronaridine induced apoptosis in cell lines 3T3 and Hep-2, even at high concentrations. The evaluation of genotoxicity by comet assay showed further that coronaridine caused minimal DNA damage in the Hep-2 tumor cell line, and the LDH test showed that it did not affect the plasma membrane. These results suggest that further investigation of coronaridine as an antitumor agent has merit. PMID:23569415

Synthesis of Scutellarein Derivatives with a Long Aliphatic Chain and Their Biological Evaluation against Human Cancer Cells.

PubMed

Ni, Guanghui; Tang, Yanling; Li, Minxin; He, Yuefeng; Rao, Gaoxiong

2018-02-01

Scutellarin is the major active flavonoid extracted from the traditional Chinese herbal medicine Erigeron breviscapus (Vant.) Hand-Mazz., which is widely used in China. Recently, accumulating evidence has highlighted the potential role of scutellarin and its main metabolite scutellarein in the treatment of cancer. To explore novel anticancer agents with high efficiency, a series of new scutellarein derivatives with a long aliphatic chain were synthesized, and the antiproliferative activities against Jurkat, HCT-116 and MDA-MB-231 cancer cell lines were assessed. Among them, compound 6a exhibited the strongest antiproliferative effects on Jurkat (IC 50 = 1.80 μM), HCT-116 (IC 50 = 11.50 μM) and MDA-MB-231 (IC 50 = 53.91 μM). In particular, 6a even showed stronger antiproliferative effects than the positive control NaAsO₂ on Jurkat and HCT-116 cell lines. The results showed that a proper long aliphatic chain enhanced the antiproliferative activity of scutellarein.

PREFACE: International Conference on Quantum Optics and Quantum Information (icQoQi) 2013

NASA Astrophysics Data System (ADS)

2014-11-01

Quantum Information can be understood as being naturally derived from a new understanding of information theory when quantum systems become information carriers and quantum effects become non negligible. Experiments and the realization of various interesting phenomena in quantum information within the established field of quantum optics have been reported, which has provided a very convenient framework for the former. Together, quantum optics and quantum information are among the most exciting areas of interdisciplinary research in modern day science which cover a broad spectrum of topics, from the foundations of quantum mechanics and quantum information science to the introduction of new types of quantum technologies and metrology. The International Conference on Quantum Optics and Quantum Information (icQoQi) 2013 was organized by the Faculty of Science, International Islamic University Malaysia with the objective of bringing together leading academic scientists, researchers and scholars in the domain of interest from around the world to share their experiences and research results about all aspects of quantum optics and quantum information. While the event was organized on a somewhat modest scale, it was in fact a rather fruitful meeting for established researchers and students as well, especially for the local scene where the field is relatively new. We would therefore, like to thank the organizing committee, our advisors and all parties for having made this event successful and last but not least would extend our sincerest gratitude to IOP for publishing these selected papers from icQoQi2013 in Journal of Physics: Conference Series.

Informed Consent for Whole Genome Sequencing: A Qualitative Analysis of Participant Expectations and Perceptions of Risks, Benefits, and Harms

PubMed Central

Tabor, Holly K.; Stock, Jacquie; Brazg., Tracy; McMillin, Margaret J.; Dent., Karin M.; Yu, Joon-Ho; Shendure, Jay; Bamshad, Michael J.

2012-01-01

Scientific evidence on the extent to which ethical concerns about privacy, confidentiality, and return of results for whole genome sequencing (WGS) are effectively conveyed by informed consent (IC) is lacking. The aim of this study was to learn, via qualitative interviews, about participant expectations and perceptions of risks, benefits, and harms of WGS. Participants in two families with Miller syndrome consented for WGS were interviewed about their experiences of the IC process and their perceptions of risks, benefits, and harms of WGS. Interviews were transcribed and analyzed for common themes. IC documents are included in the supplementary materials. Participants expressed minimal concerns about privacy and confidentiality with regard to both their participation and sharing of their WGS data in restricted access databases. Participants expressed strong preferences about how results should be returned, requesting both flexibility of the results return process and options for the types of results to be returned. Participant concerns about risks to privacy and confidentiality from broad sharing of WGS data are likely to be strongly influenced by social and medical context. In these families with a rare Mendelian syndrome, the perceived benefits of participation strongly trumped concerns about risks. Individual preferences, for results return, even within a family, varied widely. This underscores the need to develop a framework for results return that allows explicitly for participant preferences and enables modifications to preferences over time. Web-based tools that facilitate participant management of their individual research results could accommodate such a framework. PMID:22532433

Effectiveness of Six Improved Cookstoves in Reducing Household Air Pollution and Their Acceptability in Rural Western Kenya

PubMed Central

Pilishvili, Tamara; Loo, Jennifer D.; Schrag, Stephanie; Stanistreet, Debbi; Christensen, Bryan; Yip, Fuyuen; Nyagol, Ronald; Quick, Robert; Sage, Mike; Bruce, Nigel

2016-01-01

Background Household air pollution (HAP) from biomass fuel burning is linked to poor health outcomes. Improved biomass cookstoves (ICS) have the potential to improve HAP. Objectives A pre-/post- intervention study assessed the impact of six ICS on indoor air quality and acceptability of ICS to local users in rural Western Kenya. Methods We measured mean personal and kitchen level concentrations of particulate matter <2.5μm in diameter (PM2.5, μg/m3) and carbon monoxide (CO, ppm) during the 48-hour period of each ICS use in 45 households. We compared these levels to those observed with traditional 3-stone fire (TSF) use. We assessed ICS acceptability through interviews and focus groups. We evaluated association of stove type, fuel use, and factors related to cooking practices with mean kitchen PM2.5 and CO using multivariable regression. Results Stove type, exclusive ICS use (vs. concurrent TSF use), and the amount of fuel used were independently associated with kitchen PM2.5 and CO levels. Reductions (95%CI) in mean PM2.5 compared to TSF, ranged by ICS from 11.9% (-2.8–24.5) to 42.3% (32.3–50.8). Reductions in kitchen CO compared to TSF, ranged by ICS from -5.8% (-21.9–8.2) to 34.5% (23.2–44.1). Mean kitchen PM2.5 ranged from 319μg/m3 to 518μg/m3 by ICS. Women thought ICS were easy to use, more efficient, produced less smoke, and cooked faster, compared to TSF. Women also reported limitations for each ICS. Conclusions We documented reductions in HAP from ICS compared to TSF. The PM2.5 levels with ICS use were still considerably higher than WHO indoor air quality guidelines. Achieving maximal potential of ICS requires adherence to more exclusive use and addressing user reported ICS limitations. PMID:27846224

Effectiveness of Six Improved Cookstoves in Reducing Household Air Pollution and Their Acceptability in Rural Western Kenya.

PubMed

Pilishvili, Tamara; Loo, Jennifer D; Schrag, Stephanie; Stanistreet, Debbi; Christensen, Bryan; Yip, Fuyuen; Nyagol, Ronald; Quick, Robert; Sage, Mike; Bruce, Nigel

2016-01-01

Household air pollution (HAP) from biomass fuel burning is linked to poor health outcomes. Improved biomass cookstoves (ICS) have the potential to improve HAP. A pre-/post- intervention study assessed the impact of six ICS on indoor air quality and acceptability of ICS to local users in rural Western Kenya. We measured mean personal and kitchen level concentrations of particulate matter <2.5μm in diameter (PM2.5, μg/m3) and carbon monoxide (CO, ppm) during the 48-hour period of each ICS use in 45 households. We compared these levels to those observed with traditional 3-stone fire (TSF) use. We assessed ICS acceptability through interviews and focus groups. We evaluated association of stove type, fuel use, and factors related to cooking practices with mean kitchen PM2.5 and CO using multivariable regression. Stove type, exclusive ICS use (vs. concurrent TSF use), and the amount of fuel used were independently associated with kitchen PM2.5 and CO levels. Reductions (95%CI) in mean PM2.5 compared to TSF, ranged by ICS from 11.9% (-2.8-24.5) to 42.3% (32.3-50.8). Reductions in kitchen CO compared to TSF, ranged by ICS from -5.8% (-21.9-8.2) to 34.5% (23.2-44.1). Mean kitchen PM2.5 ranged from 319μg/m3 to 518μg/m3 by ICS. Women thought ICS were easy to use, more efficient, produced less smoke, and cooked faster, compared to TSF. Women also reported limitations for each ICS. We documented reductions in HAP from ICS compared to TSF. The PM2.5 levels with ICS use were still considerably higher than WHO indoor air quality guidelines. Achieving maximal potential of ICS requires adherence to more exclusive use and addressing user reported ICS limitations.

The photoionization mechanism of LINERs - Stellar and nonstellar

NASA Technical Reports Server (NTRS)

Ho, Luis C.; Filippenko, Alexei V.

1993-01-01

We present high quality spectroscopic observations of a sample of 14 LINERs. Starlight removal is achieved by the subtraction of a suitable absorption-line 'template' galaxy, allowing accurate measurements of emission lines. We use these line fluxes to examine the possible excitation mechanisms of LINERs. We suggest that LINERs with weak forbidden O I 6300-A emission may be H II regions photoionized by unusually hot O-type stars. LINERs with forbidden O I/H-alpha approximately greater than 1/6 may be powered by photoionization from a nonstellar continuum. This is supported by the detection of broad H-alpha emission, a correlation between line width and critical density, and pointlike X-ray emission in several of these objects.

Cytotoxic, Antiproliferative and Apoptotic Effects of Perillyl Alcohol and Its Biotransformation Metabolite on A549 and HepG2 Cancer Cell Lines.

PubMed

Oturanel, Ceren E; Kıran, İsmail; Özşen, Özge; Çiftçi, Gülşen A; Atlı, Özlem

2017-01-01

A monoterpene, perillyl alcohol, has attracted attention in medicinal chemistry since it exhibited chemo-preventive and therapeutic properties against a variety of cancers. In the present work, it was aimed to obtain derivatives of perillyl alcohol through microbial biotransformation and investigate their anticancer activities against A549 and HepG2 cancer cell lines. Biotransformation studies were carried out in a α-medium for 7 days at 25oC. XTT assay was performed to investigate the anticancer activities of perillyl alcohol and its biotransformation metabolite, dehydroperillic acid, against A549 and HepG2 cell lines and their selectivity using healthy cell line, NIH/3T3. Cell proliferation ELISA, BRDU (colorimetric) assay was used for measurement of proliferation in replicative cells in which DNA synthesis occurs. Flow cytometric analyses were also carried out for measuring apoptotic cell percentages, caspase 3 activation and mitochondrial membrane potential. Biotransformation of perillyl alcohol with Fusarium culmorum yielded dehydroperillic acid in a yield of 20.4 %. In in vitro anticancer studies, perillyl alcohol was found to exert cytotoxicity against HepG2 cell line with an IC50 value of 409.2 μg/mL. However, this effect was not found to be selective because of its higher IC50 (250 μg/mL) value against NIH/3T3 cell line. On the other hand, dehydroperillic acid was found to be effective and also selective against A549 cell line with an IC50 value of 125 μg/mL and a selectivity index (SI) value of 400. Apoptosis inducing effects of dehydroperillic acid was better in A549 cell line. Dehydroperillic acid may be a good candidate for therapy of lung adenocarcinoma and may show this anticancer activity by inducing apoptosis. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Broad and potent HIV-1 neutralization by a human antibody that binds the gp41-gp120 interface

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

Huang, Jinghe; Kang, Byong H.; Pancera, Marie

The isolation of human monoclonal antibodies is providing important insights into the specificities that underlie broad neutralization of HIV-1 (reviewed in ref. 1). Here we report a broad and extremely potent HIV-specific monoclonal antibody, termed 35O22, which binds a novel HIV-1 envelope glycoprotein (Env) epitope. 35O22 neutralized 62% of 181 pseudoviruses with a half-maximum inhibitory concentration (IC 50) <50 μg ml -1. The median IC 50 of neutralized viruses was 0.033 μg ml -1, among the most potent thus far described. 35O22 did not bind monomeric forms of Env tested, but did bind the trimeric BG505 SOSIP.664. Mutagenesis and amore » reconstruction by negative-stain electron microscopy of the Fab in complex with trimer revealed that it bound to a conserved epitope, which stretched across gp120 and gp41. The specificity of 35O22 represents a novel site of vulnerability on HIV Env, which serum analysis indicates to be commonly elicited by natural infection. Binding to this new site of vulnerability may thus be an important complement to current monoclonal-antibody-based approaches to immunotherapies, prophylaxis and vaccine design.« less

A very luminous magnetar-powered supernova associated with an ultra-long γ-ray burst.

PubMed

Greiner, Jochen; Mazzali, Paolo A; Kann, D Alexander; Krühler, Thomas; Pian, Elena; Prentice, Simon; Olivares E, Felipe; Rossi, Andrea; Klose, Sylvio; Taubenberger, Stefan; Knust, Fabian; Afonso, Paulo M J; Ashall, Chris; Bolmer, Jan; Delvaux, Corentin; Diehl, Roland; Elliott, Jonathan; Filgas, Robert; Fynbo, Johan P U; Graham, John F; Guelbenzu, Ana Nicuesa; Kobayashi, Shiho; Leloudas, Giorgos; Savaglio, Sandra; Schady, Patricia; Schmidl, Sebastian; Schweyer, Tassilo; Sudilovsky, Vladimir; Tanga, Mohit; Updike, Adria C; van Eerten, Hendrik; Varela, Karla

2015-07-09

A new class of ultra-long-duration (more than 10,000 seconds) γ-ray bursts has recently been suggested. They may originate in the explosion of stars with much larger radii than those producing normal long-duration γ-ray bursts or in the tidal disruption of a star. No clear supernova has yet been associated with an ultra-long-duration γ-ray burst. Here we report that a supernova (SN 2011kl) was associated with the ultra-long-duration γ-ray burst GRB 111209A, at a redshift z of 0.677. This supernova is more than three times more luminous than type Ic supernovae associated with long-duration γ-ray bursts, and its spectrum is distinctly different. The slope of the continuum resembles those of super-luminous supernovae, but extends further down into the rest-frame ultraviolet implying a low metal content. The light curve evolves much more rapidly than those of super-luminous supernovae. This combination of high luminosity and low metal-line opacity cannot be reconciled with typical type Ic supernovae, but can be reproduced by a model where extra energy is injected by a strongly magnetized neutron star (a magnetar), which has also been proposed as the explanation for super-luminous supernovae.

Assimilative and non-assimilative color spreading in the watercolor configuration.

PubMed

Kimura, Eiji; Kuroki, Mikako

2014-01-01

A colored line flanking a darker contour will appear to spread its color onto an area enclosed by the line (watercolor effect). The watercolor effect has been characterized as an assimilative effect, but non-assimilative color spreading has also been demonstrated in the same spatial configuration; e.g., when a black inner contour (IC) is paired with a blue outer contour (OC), yellow color spreading can be observed. To elucidate visual mechanisms underlying these different color spreading effects, this study investigated the effects of luminance ratio between the double contours on the induced color by systematically manipulating the IC and the OC luminance (Experiment 1) as well as the background luminance (Experiment 2). The results showed that the luminance conditions suitable for assimilative and non-assimilative color spreading were nearly opposite. When the Weber contrast of the IC to the background luminance (IC contrast) was smaller in size than that of the OC (OC contrast), the induced color became similar to the IC color (assimilative spreading). In contrast, when the OC contrast was smaller than or equal to the IC contrast, the induced color became yellow (non-assimilative spreading). Extending these findings, Experiment 3 showed that bilateral color spreading, i.e., assimilative spreading on one side and non-assimilative spreading on the other side, can also be observed in the watercolor configuration. These results suggest that the assimilative and the non-assimilative spreading were mediated by different visual mechanisms. The properties of the assimilative spreading are consistent with the model proposed to account for neon color spreading (Grossberg and Mingolla, 1985) and extended for the watercolor effect (Pinna and Grossberg, 2005). However, the present results suggest that additional mechanisms are needed to account for the non-assimilative color spreading.

1990 MTT-S International Microwave Symposium and Exhibition and Microwave and Millimeter-Wave Monolithic IC Symposium, Dallas, TX, May 7-10, 1990, Proceedings

NASA Astrophysics Data System (ADS)

McQuiddy, David N., Jr.; Sokolov, Vladimir

1990-12-01

The present conference discusses microwave filters, lightwave technology for microwave antennas, planar and quasi-planar guides, mixers and VCOs, cavity filters, discontinuity and coupling effects, control circuits, power dividers and phase shifters, microwave ICs, biological effects and medical applications, CAD and modeling for MMICs, directional couplers, MMIC design trends, microwave packaging and manufacturing, monolithic ICs, and solid-state devices and circuits. Also discussed are microwave and mm-wave superconducting technology, MICs for communication systems, the merging of optical and microwave technologies, microwave power transistors, ferrite devices, network measurements, advanced transmission-line structures, FET devices and circuits, field theory of IC discontinuities, active quasi-optical techniques, phased-array techniques and circuits, nonlinear CAD, sub-mm wave devices, and high power devices.

Copper (II) complexes of bidentate ligands exhibit potent anti-cancer activity regardless of platinum sensitivity status.

PubMed

Wehbe, Mohamed; Lo, Cody; Leung, Ada W Y; Dragowska, Wieslawa H; Ryan, Gemma M; Bally, Marcel B

2017-12-01

Insensitivity to platinum, either through inherent or acquired resistance, is a major clinical problem in the treatment of many solid tumors. Here, we explored the therapeutic potential of diethyldithiocarbamate (DDC), pyrithione (Pyr), plumbagin (Plum), 8-hydroxyquinoline (8-HQ), clioquinol (CQ) copper complexes in a panel of cancer cell lines that differ in their sensitivity to platins (cisplatin/carboplatin) using a high-content imaging system. Our data suggest that the copper complexes were effective against both platinum sensitive (IC 50  ~ 1 μM platinum) and insensitive (IC 50  > 5 μM platinum) cell lines. Furthermore, copper complexes of DDC, Pyr and 8-HQ had greater therapeutic activity compared to the copper-free ligands in all cell lines; whereas the copper-dependent activities of Plum and CQ were cell-line specific. Four of the copper complexes (Cu(DDC) 2 , Cu(Pyr) 2 , Cu(Plum) 2 and Cu(8-HQ) 2 ) showed IC 50 values less than that of cisplatin in all tested cell lines. The complex copper DDC (Cu(DDC) 2 ) was selected for in vivo evaluation due to its low nano-molar range activity in vitro and the availability of an injectable liposomal formulation. Liposomal (Cu(DDC) 2 ) was tested in a fast-growing platinum-resistant A2780-CP ovarian xenograft model and was found to achieve a statistically significant reduction (50%; p < 0.05) in tumour size. This work supports the potential use of copper-based therapeutics to treat cancers that are insensitive to platinum drugs.

Synthesis of novel forskolin isoxazole derivatives with potent anti-cancer activity against breast cancer cell lines.

PubMed

Burra, Srinivas; Voora, Vani; Rao, Ch Prasad; Vijay Kumar, P; Kancha, Rama Krishna; David Krupadanam, G L

2017-09-15

Forskolin C 1 -isoxazole derivatives (3,5-regioisomers) (11a-e, 14, 15a-h and 15, 16a-g) were synthesized regioselectively by adopting 1,3-dipolar cycloadditions. These derivatives were tested using estrogen receptor positive breast cancer cell lines MCF-7 and BT-474. Majority of the compounds exhibited activity against the p53-positive MCF-7 breast cancer cells but not against the p53-negative BT-474 breast cancer cells. Among forskolin derivatives, compounds 11a, 11c, 14a, 14f, 14g, 14h, 15b, 16g and 17b exhibited higher anti-cancer activity against MCF-7 cell line with an IC 50 ≤1µM. The derivative 14f exhibited highest activity in both p53-positive (MCF-7) and p53-negative (BT-474) breast cancer cell lines with an IC 50 of 0.5µM. Copyright © 2017. Published by Elsevier Ltd.

DISCOVERY OF THE TRANSITION OF A MINI-BROAD ABSORPTION LINE INTO A BROAD ABSORPTION LINE IN THE SDSS QUASAR J115122.14+020426.3

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

Hidalgo, Paola Rodriguez; Eracleous, Michael; Charlton, Jane

We present the detection of a rare case of dramatic strengthening in the UV absorption profiles in the spectrum of the quasar J115122.14+020426.3 between observations {approx}2.86 yr apart in the quasar rest frame. A spectrum obtained in 2001 by the Sloan Digital Sky Survey shows a C IV ''mini-broad'' absorption line (FWHM = 1220 km s{sup -1}) with a maximum blueshift velocity of {approx}9520 km s{sup -1}, while a later spectrum from the Very Large Telescope shows a significantly broader and stronger absorption line, with a maximum blueshift velocity of {approx}12, 240 km s{sup -1} that qualifies as a broadmore » absorption line. A similar variability pattern is observed in two additional systems at lower blueshifted velocities and in the Ly{alpha} and N V transitions as well. One of the absorption systems appears to be resolved and shows evidence for partial covering of the quasar continuum source (C{sub f} {approx} 0.65), indicating a transverse absorber size of, at least, {approx}6 Multiplication-Sign 10{sup 16} cm. In contrast, a cluster of narrower C IV lines appears to originate in gas that fully covers the continuum and broad emission line sources. There is no evidence for changes in the centroid velocity of the absorption troughs. This case suggests that at least some of the absorbers that produce ''mini-broad'' and broad absorption lines in quasar spectra do not belong to intrinsically separate classes. Here, the ''mini-broad'' absorption line is most likely interpreted as an intermediate phase before the appearance of a broad absorption line due to their similar velocities. While the current observations do not provide enough constraints to discern among the possible causes for this variability, future monitoring of multiple transitions at high resolution will help achieve this goal.« less

Super-massive binary black holes and emission lines in active galactic nuclei

NASA Astrophysics Data System (ADS)

Popović, Luka Č.

2012-02-01

It is now agreed that mergers play an essential role in the evolution of galaxies and therefore that mergers of supermassive black holes (SMBHs) must have been common. We see the consequences of past supermassive binary black holes (SMBs) in the light profiles of so-called 'core ellipticals' and a small number of SMBs have been detected. However, the evolution of SMBs is poorly understood. Theory predicts that SMBs should spend a substantial amount of time orbiting at velocities of a few thousand kilometers per second. If the SMBs are surrounded by gas observational effects might be expected from accretion onto one or both of the SMBHs. This could result in a binary Active Galactic Nucleus (AGN) system. Like a single AGN, such a system would emit a broad band electromagnetic spectrum and broad and narrow emission lines. The broad emission spectral lines emitted from AGNs are our main probe of the geometry and physics of the broad line region (BLR) close to the SMBH. There is a group of AGNs that emit very broad and complex line profiles, showing two displaced peaks, one blueshifted and one redshifted from the systemic velocity defined by the narrow lines, or a single such peak. It has been proposed that such line shapes could indicate an SMB system. We discuss here how the presence of an SMB will affect the BLRs of AGNs and what the observational consequences might be. We review previous claims of SMBs based on broad line profiles and find that they may have non-SMB explanations as a consequence of a complex BLR structure. Because of these effects it is very hard to put limits on the number of SMBs from broad line profiles. It is still possible, however, that unusual broad line profiles in combination with other observational effects (line ratios, quasi-periodical oscillations, spectropolarimetry, etc.) could be used for SMBs detection. Some narrow lines (e.g., [O III]) in some AGNs show a double-peaked profile. Such profiles can be caused by streams in the Narrow Line Region (NLR), but may also indicate the presence of a kilo-parsec scale mergers. A few objects indicated as double-peaked narrow line emitters are confirmed as kpc-scale margers, but double-peaked narrow line profiles are mostly caused by the complex NLR geometry. We briefly discuss the expected line profile of broad Fe Kα that probably originated in the accretion disk(s) around SMBs. This line may also be very complex and indicate the complex disk geometry or/and an SMB presence. Finally we consider rare configurations where a SMB system might be gravitationally lensed by a foreground galaxy, and discuss the expected line profiles in these systems.

Selectivity of Pinus sylvestris extract and essential oil to estrogen-insensitive breast cancer cells Pinus sylvestris against cancer cells

PubMed Central

Hoai, Nguyen Thi; Duc, Ho Viet; Thao, Do Thi; Orav, Anne; Raal, Ain

2015-01-01

Background: So far, the anticancer action of pine tree extracts has mainly been shown for the species distributed widely around the Asian countries. Objective: Therefore, this study was performed to examine the potential cytotoxicity of Scots pine (Pinus sylvestris L.) native also to the European region and growing widely in Estonia. Materials and Methods: The cytotoxic activity of methanol extract and essential oil of Scots pine needles was determined by sulforhodamine B assay in different human cancer cell lines. Results: This needle extract was found to suppress the viability of several human cancer cell lines showing some selectivity to estrogen receptor negative breast cancer cells, MDA-MB-231(half maximal inhibitory concentration [IC50] 35 μg/ml) in comparison with estrogen receptor-positive breast cancer cells, MCF-7 (IC50 86 μg/ml). It is the strongest cytotoxic effect at all measured, thus far for the needles and leaves extracts derived from various pine species, and is also the first study comparing the anticancer effects of pine tree extracts on molecularly different human breast cancer cells. The essential oil showed the stronger cytotoxic effect to both negative and positive breast cancer cell lines (both IC50 29 μg/ml) than pine extract (IC50 42 and 80 μg/ml, respectively). Conclusion: The data from this report indicate that Scots pine needles extract and essential oil exhibits some potential as chemopreventive or chemotherapeutic agent for mammary tumors unresponsive to endocrine treatment. PMID:26664017

Studies on the secondary metabolites of a Pseudoalteromonas sp. isolated from sediments collected at the northeastern coast of Brazil.

PubMed

Arthaud, Isabelle D B; Rodrigues, Felipe A R; Jimenez, Paula C; Montenegro, Raquel C; Angelim, Alysson L; Maciel, Vânia M M; Silveira, Edilberto R; Freitas, Hozana P S; Sousa, Thiciana S; Pessoa, Otília D L; Lotufo, Tito M C; Costa-Lotufo, Letícia V

2012-02-01

Continuing search for anticancer compounds from the marine environment, we have studied microorganisms that inhabit intertidal sediments of the northeastern Brazilian coast. Of the 32 strains isolated, 13 were selected for biological evaluation of their crude extracts. The acetate extract obtained from a Gram-negative bacterium was strongly active against cancer cell lines with IC(50) values that ranged from 0.04 (HL60 leukemia cells) to 0.26 μg/ml (MDA MB-435 melanoma cells). The bacterium was identified as a Pseudoalteromonas sp. based on 16S rRNA gene sequencing. A bioassay-guided fractionation of the active extract led to the isolation of prodigiosin, a well-known tripyrrole red pigment with immunosuppressive and anticancer activities. Further experiments with ErbB-2 overexpressing cell lines, including HB4a-C3.6 (moderate overexpression), HB4a-C5.2 (high overexpression), and the parental HB4a cell line, were performed. Prodigiosin was moderately active toward HB4a cells with an IC(50) of 4.6 μg/ml, while it was 115 and 18 times more active toward HB4a-C3.6 cells (IC(50) of 0.04 μg/ml) and HB4a-C5.2 (IC(50) of 0.26 μg/ml) cells, respectively. These data suggest that, in spite of its previously described apoptosis-inducing properties, prodigiosin can selectively recognize cells overexpressing ErbB-2, which could be highly appealing in human breast cancer therapy. Copyright © 2012 Verlag Helvetica Chimica Acta AG, Zürich.

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

Laycock, Silas; Cappallo, Rigel; Oram, Kathleen

We report the discovery of a large amplitude (factor of ∼100) X-ray transient (IC 10 X-2, CXOU J002020.99+591758.6) in the nearby dwarf starburst galaxy IC 10 during our Chandra monitoring project. Based on the X-ray timing and spectral properties, and an optical counterpart observed with Gemini, the system is a high-mass X-ray binary consisting of a luminous blue supergiant and a neutron star. The highest measured luminosity of the source was 1.8 × 10{sup 37} erg s{sup –1}during an outburst in 2003. Observations before, during, and after a second outburst in 2010 constrain the outburst duration to be less thanmore » 3 months (with no lower limit). The X-ray spectrum is a hard power law (Γ = 0.3) with fitted column density (N{sub H} = 6.3 × 10{sup 21} atom cm{sup –2}), consistent with the established absorption to sources in IC 10. The optical spectrum shows hydrogen Balmer lines strongly in emission at the correct blueshift (-340 km s{sup –1}) for IC 10. The N III triplet emission feature is seen, accompanied by He II [4686] weakly in emission. Together these features classify the star as a luminous blue supergiant of the OBN subclass, characterized by enhanced nitrogen abundance. Emission lines of He I are seen, at similar strength to Hβ. A complex of Fe II permitted and forbidden emission lines are seen, as in B[e] stars. The system closely resembles galactic supergiant fast X-ray transients, in terms of its hard spectrum, variability amplitude, and blue supergiant primary.« less

Hidden Broad-Line Seyfert 2 Galaxies in the CFA and 12 μM Samples

NASA Astrophysics Data System (ADS)

Tran, Hien D.

2001-06-01

We report the results of a spectropolarimetric survey of the CfA and 12 μm samples of Seyfert 2 (S2) galaxies. Polarized (hidden) broad-line regions (HBLRs) are confirmed in a number of galaxies, and several new cases (F02581-1136, MCG -3-58-7, NGC 5995, NGC 6552, NGC 7682) are reported. The 12 μm S2 galaxy sample shows a significantly higher incidence of HBLRs (50%) than its CfA counterpart (30%), suggesting that the latter may be incomplete in hidden active galactic nuclei. Compared to the non-HBLR S2 galaxies, the HBLR S2 galaxies display distinctly higher radio power relative to their far-infrared output and hotter dust temperature as indicated by the f25/f60 color. However, the level of obscuration is indistinguishable between the two types of S2 galaxies. These results strongly support the existence of two intrinsically different populations of S2 galaxies: one harboring an energetic, hidden S1 nucleus with a broad-line region and the other a ``pure'' S2 galaxy, with a weak or absent S1 nucleus and a strong, perhaps dominating starburst component. Thus, the simple purely orientation-based unification model is not applicable to all Seyfert galaxies.

ORFEUS spectroscopy of the O BT VI lines in symbiotic stars and the Raman scattering process

NASA Astrophysics Data System (ADS)

Schmid, H. M.; Krautter, J.; Appenzeller, I.; Barnstedt, J.; Dumm, T.; Fromm, A.; Gölz, M.; Grewing, M.; Gringel, W.; Haas, C.; Hopfensitz, W.; Kappelmann, N.; Krämer, G.; Lindenberger, A.; Mandel, H.; Mürset, U.; Schild, H.; Schmutz, W.; Widmann, H.

1999-08-01

We present orfeus spectra of the O vi lambda lambda 1032,1038 emission lines in the symbiotic stars AG Dra, V1016 Cyg, RR Tel, CD-43(deg) 14304, AG Peg and Z And. The O vi emission lines can convert into broad and highly polarized emission lines at lambda 6825 and lambda 7082 in a Raman scattering process by neutral hydrogen. From a comparison of direct and Raman scattered radiation we extract new information on the scattering geometry in symbiotic systems. The nebular O vi emission lines are in all objects redshifted by about +40 km s(-1) . This can be explained as a radiative line transfer effect in a slowly expanding emission region. A comparable redshift is measured in the Raman scattered O vi lines. In AG Peg the O vi emissions show beside a narrow nebular line a broad component from a fast stellar wind outflow. Many interstellar absorption lines of molecular hydrogen are detected, particularly near the O vi lambda 1038 component. With model calculations we investigate their impact on the O vi lines. From the dereddened line fluxes of the direct and Raman scattered O vi lines we derive the scattering efficiency, which is defined as photon flux ratio N_Raman/N_O VI. The efficiencies derived for RR Tel, V1016 Cyg and Z And indicate that about 30% of the released O vi lambda 1032 photons interact with the neutral scattering region. The efficiencies for AG Dra and CD-43(deg14304) are much higher, which may suggest that the O vi nebulosity is embedded in a H(0) -region. The D-type system RR Tel shows strong line profile differences between the direct O vi emission, which is single-peaked, and the Raman scattered emission, which is double-peaked. This indicates that the neutral scattering region in RR Tel ``sees'' different O vi line profiles, implying that the O vi nebulosity is far from spherically symmetric. In a tentative model we suggest for RR Tel an O vi flow pattern where material streams from the cool giant towards the hot component, which further accelerates the gas radially. For the S-type systems AG Dra, CD-43(deg14304) and Z And the line profile differences between the direct and the Raman scattered O vi emissions are less pronounced. This may suggest that the O vi profiles depend less on the emission direction than in the D-type system RR Tel. For AG Peg we detect for the first time the Raman scattered emission at lambda 6825. The Raman line shows a narrow, nebular component as the O vi line, but no equivalent emission to the broad O vi wind component. The higher conversion efficiency for the narrow component indicates that the nebular O vi emission is significantly closer to the cool giant than the hot, mass losing component, and strongly supports previous colliding wind models for this object. Based on observations taken during the orfeus-spas i and orfeus-spas ii space shuttle missions, and ground based data collected at the ESO 2.2m and 3.6m telescopes at La Silla, Chile, and the 4.2m William Herschel Telescope at La Palma, Canary Islands. ESO observations were granted for the programs 52.7-040 and 58.D-0866.

Development of tuberculosis infection control guidelines in a pediatric HIV clinic in sub-Saharan Africa.

PubMed

Carlucci, J G; Jin, L; Sanders, J E; Mohapi, E Q; Mandalakas, A M

2015-03-21

A well-established pediatric human immunodeficiency virus (HIV) clinic in Lesotho with initial infection control (IC) measures prioritizing blood-borne disease. In line with international recommendations, services have been expanded to include the management of patients with tuberculosis (TB). The creation of comprehensive IC guidelines with an emphasis on TB has become a priority. To provide a model for developing and implementing IC guidelines in ambulatory care facilities in limited-resource settings with high HIV and TB prevalence. Activities: An IC plan that includes guidance covering both general IC measures and TB-specific guidelines was created by integrating local and international recommendations and emphasizing the importance of administrative measures, environmental controls, and disease-specific precautions. An interdisciplinary committee was established to oversee its implementation, monitoring, and evaluation. Development and implementation of IC guidelines in resource-limited settings are feasible and should be a priority in high HIV and TB prevalence areas. Education should be the cornerstone of such endeavors. Many interventions can be implemented with minimal expertise and material resources. Administrative support and institutional investment are essential to the sustainability of an effective IC program.

Highly potent artemisinin-derived dimers and trimers: Synthesis and evaluation of their antimalarial, antileukemia and antiviral activities.

PubMed

Reiter, Christoph; Fröhlich, Tony; Gruber, Lisa; Hutterer, Corina; Marschall, Manfred; Voigtländer, Cornelia; Friedrich, Oliver; Kappes, Barbara; Efferth, Thomas; Tsogoeva, Svetlana B

2015-09-01

New pharmaceutically active compounds can be obtained by modification of existing drugs to access more effective agents in the wake of drug resistance amongst others. To achieve this goal the concept of hybridization was established during the last decade. We employed this concept by coupling two artemisinin-derived precursors to obtain dimers or trimers with increased in vitro activity against Plasmodiumfalciparum 3D7 strain, leukemia cells (CCRF-CEM and multidrug-resistant subline CEM/ADR5000) and human cytomegalovirus (HCMV). Dimer 4 (IC50 of 2.6 nM) possess superior antimalarial activity compared with its parent compound artesunic acid(3) (IC50 of 9.0 nM). Dimer5 and trimers6 and 7 display superior potency against both leukemia cell lines (IC50 up to 0.002 μM for CCRF-CEM and IC50 up to 0.20 μM for CEM/ADR5000) and are even more active than clinically used doxorubicin (IC50 1.61 μM for CEM/ADR5000). With respect to anti-HCMV activity, trimer6 is the most efficient hybrid (IC50 0.04 μM) outperforming ganciclovir (IC50 2.6 μM), dihydroartemisinin(IC50 >10 μM) and artesunic acid (IC50 3.8 μM). Copyright © 2015 Elsevier Ltd. All rights reserved.

Developing a Decision Support System for Flood Response: NIMS/ICS Fundamentals

NASA Astrophysics Data System (ADS)

Gutenson, J. L.; Zhang, X.; Ernest, A. N. S.; Oubeidillah, A.; Zhu, L.

2015-12-01

Effective response to regional disasters such as floods requires a multipronged, non-linear approach to reduce loss of life, property and harm to the environment. These coordinated response actions are typically undertaken by multiple jurisdictions, levels of government, functional agencies and other responsible entities. A successful response is highly dependent on the effectiveness and efficiency of each coordinated response action undertaken across a broad spectrum of organizations and activities. In order to provide a unified framework for those responding to incidents or planned events, FEMA provides a common and flexible approach for managing incidents, regardless of cause, size, location or complexity, referred to as the National Incident Management System (NIMS). Integral to NIMS is the Incident Command System (ICS), which establishes a common, pre-defined organizational structure to ensure coordination and management of procedures, resources and communications, for efficient incident management. While being both efficient and rigorous, NIMS, and ICS to a lesser extent, is an inherently complex framework that requires significant amount of training for planners, responders and managers to master, especially considering the wide array of incident types that Local Emergency Planning Committees (LEPCs) must be prepared to respond to. The existing Water-Wizard Decision Support System (DSS), developed to support water distribution system recovery operations for Decontamination (Decon), Operational Optimization (WDS), and Economic Consequence Assessment (Econ), is being evolved to integrate incident response functions. Water-Wizard runs on both mobile and desktop devices, and is being extended to utilize smartphone and mobile device specific data streams (e.g GPS location) to augment its fact-base in real-time for situational-aware DSS recommendations. In addition, the structured NIMS and ICS frameworks for incident management and response are being incorporated into the Water-Wizard knowledgebase, with a mid-term goal of integrating flood-specific emergency response domain knowledge to provide a real-time flood responder decision support.

IC(B,T,STRAIN) Characterisation of a Nb3Sn Internal Tin Strand with Enhanced Specification for Use in Fusion Conductors

NASA Astrophysics Data System (ADS)

Pasztor, G.; Bruzzone, P.

2004-06-01

The dc performance of a recently produced internal tin route Nb3Sn strand with enhanced specification is studied extensively and compared with predecessor wires manufactured by the suppliers for the ITER Model Coils in 1996. The wire has been selected for use in a full size, developmental cable-in-conduit conductor sample, which is being tested in the SULTAN Test Facility. The critical current, Ic, and the index of the current/voltage characteristic, n, are measured over a broad range of field and temperature, using ITER standard sample holders, made of TiAlV grooved cylinders. The behavior of Ic versus applied tensile strain is also investigated at 4.2 K and 12 T, on straight specimens. Scaling law parameters are drawn from the fit of the experimental results. The implications of the test results to the design of the fusion conductors are discussed.

Differential sensitivity of melanoma cell lines with BRAFV600E mutation to the specific Raf inhibitor PLX4032

PubMed Central

2010-01-01

Blocking oncogenic signaling induced by the BRAFV600E mutation is a promising approach for melanoma treatment. We tested the anti-tumor effects of a specific inhibitor of Raf protein kinases, PLX4032/RG7204, in melanoma cell lines. PLX4032 decreased signaling through the MAPK pathway only in cell lines with the BRAFV600E mutation. Seven out of 10 BRAFV600E mutant cell lines displayed sensitivity based on cell viability assays and three were resistant at concentrations up to 10 μM. Among the sensitive cell lines, four were highly sensitive with IC50 values below 1 μM, and three were moderately sensitive with IC50 values between 1 and 10 μM. There was evidence of MAPK pathway inhibition and cell cycle arrest in both sensitive and resistant cell lines. Genomic analysis by sequencing, genotyping of close to 400 oncogeninc mutations by mass spectrometry, and SNP arrays demonstrated no major differences in BRAF locus amplification or in other oncogenic events between sensitive and resistant cell lines. However, metabolic tracer uptake studies demonstrated that sensitive cell lines had a more profound inhibition of FDG uptake upon exposure to PLX4032 than resistant cell lines. In conclusion, BRAFV600E mutant melanoma cell lines displayed a range of sensitivities to PLX4032 and metabolic imaging using PET probes can be used to assess sensitivity. PMID:20406486

Relations between broad-band linear polarization and Ca II H and K emission in late-type dwarf stars

NASA Technical Reports Server (NTRS)

Huovelin, Juhani; Saar, Steven H.; Tuominen, Ilkka

1988-01-01

Broadband UBV linear polarization data acquired for a sample of late-type dwarfs are compared with contemporaneous measurements of Ca II H and K line core emission. A weighted average of the largest values of the polarization degree is shown to be the best parameter for chromospheric activity diagnosis. The average maximum polarization in the UV is found to increase from late-F to late-G stars. It is noted that polarization in the U band is considerably more sensitive to activity variations than that in the B or V bands. The results indicate that stellar magnetic fields and the resulting saturation in the Zeeman-sensitive absorption lines are the most probably source of linear polarization in late-type main-sequence stars.

Toxicological evaluation of the natural products and some semisynthetic derivatives of Heterotheca inuloides Cass (Asteraceae).

PubMed

Rodríguez-Chávez, José Luis; Coballase-Urrutia, Elvia; Sicilia-Argumedo, Gloria; Ramírez-Apan, Teresa; Delgado, Guillermo

2015-12-04

Heterotheca ineuloides Cass (Asteraceae), popularly known as árnica mexicana, is widely used in Mexican traditional medicine to treat bruises, dermatological problems, rheumatic pains, and other disorders as cancer. The major constituents in H. inuloides are cadinane type sesquiterpenes, flavonoids and phytosterols. Compounds with a cadinane skeleton have been proved to possess cytotoxic activity against human-tumor cell lines and brine shrimp, and display toxic effects in different animal species. Although this plant has been widely used, there is little available information on the safety and toxicity especially of pure compounds. Evaluate the potential toxicity of the natural products isolated from H. inuloides and some semisynthetic derivatives. The toxic aspects of the following natural products isolated from dried flowers of H. inuloides: 7-hydroxy-3,4-dihydrocadalene (1), 7-hydroxycadalene (2), 3,7-dihydroxy-3(4H)-isocadalen-4-one (3), (1R,4R)-1-hydroxy-4H-1,2,3,4- tetrahydrocadalen-15-oic acid (4), D-chiro-inositol (5), quercetin (6), quercetin-3,7,3'-trimethyl ether (7), quercetin-3,7,3',4'-tetramethyl ether (8), eriodictyol-7,4'-dimethyl ether (9), α-spinasterol (10), caryolan-1,9β-diol (11) and 7-(3,3-dimethylallyloxy)-coumarin (12) as well as the toxic aspects of the semisynthetic compounds 7-acetoxy-3,4-dihydrocadalene (13), 7-benzoxy-3,4-dihydrocadalene (14), 7-acetoxycadalene (15), 7-benzoxycadalene (16), quercetin pentaacetate (17), 7-hydroxycalamenene (18), 3,8-dimethyl-5-(1-methylethyl)-1,2-naphthoquinone (19), and 4-isopropyl-1,6-dimethylbenzo[c]oxepine-7,9-dione (20). Toxic activities of compounds were determined by sulforhodamine B (SRB) assay, Artemia salina assay, RAW264.7 macrophage cells. Additionally, the acute toxicity in mouse of compound 1, the major natural sesquiterpene isolated from the acetone extract, was evaluated. The best cytotoxicity activity was observed for mansonone C (19) on K562 cell line with IC50 1.45 ± 0.14 μM, for 7-hydroxycadalene (2) on HCT-15 cell line with IC50 18.89 ± 1.2 μM, and for quercetin pentaacetate (17) on MCF-7 cell line with IC50 22.57 ± 2.4 μM. Sesquiterpenes mansonone C (19) and 7-hydroxy-3,4-dihydrocadalene (1) caused the strongest deleterious effects against A. salina with IC50 39.4 ± 1.07, and 45.47 ± 1.74 μM, respectively. The number of viable RAW 264.7 cells was reduced with sesquiterpenes 1 and 2 by more than 90%. In addition, the acute study of 1 revealed no lethal effects at 300 mg/kg body weight, however, a reduction in the body weight of mice, morphological changes in the tissues of the liver and kidney and toxic signs were observed at very high doses (2000 mg/kg). The results provided evidence for the cytotoxicity of Mexican arnica (H. inuloides) metabolites and may be correlated with one of the popular uses of this plant, in traditional Mexican medicine, as anticancer remedy. Among the active compounds contained in the acetone extract, the cytotoxic activity is mainly ascribable to cadinene type sesquiterpenes. In addition, evidence of acute toxicity suggests that 7-hydroxy-3,4-dihydrocadalene (1) may lead to toxicity at very high doses. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Lectin histochemistry of the rat lymph node: visualisation of stroma, blood vessels, sinuses, and macrophages. A contribution to the concept of an immune accessory role of sinus-lining endothelia.

PubMed

Düllmann, Jochen; Van Damme, Els J M; Peumans, Willy J; Ziesenitz, Maike; Schumacher, Udo

2002-01-01

The lectin Chelidonium majus agglutinin (CMA) was previously shown to visualise endothelia of all blood vessels and those lining sinuses of red pulp, stromal reticular meshwok (RM) and dendritic cells of lymphatic follicles in white pulp of the spleen in rats. The aim of the present study was the analysis of CMA and some other lectins in labelling RM, vascular structures and macrophages in lymph nodes of rats. It appeared that CMA stained the entire RM, dendritic cells, lining cells of sinuses and all types of blood vessels. Sinus-lining cells of lymph nodes were labelled with CMA and mannose-, GalNac-, and sialic acid-specific lectins. Moreover, lymph node macrophages were labelled above all by mannose specific lectins. The broad lectin-binding pattern of sinuses--not observed in rat spleen- and CMA-reactivity of both sinus-lining and dendritic cells corroborates the hypothesis that lymph node sinus-lining endothelia are precursors or a special type of immune accessory cells.

CRISPR/Cas9 mutagenesis invalidates a putative cancer dependency targeted in on-going clinical trials.

PubMed

Lin, Ann; Giuliano, Christopher J; Sayles, Nicole M; Sheltzer, Jason M

2017-03-24

The Maternal Embryonic Leucine Zipper Kinase (MELK) has been reported to be a genetic dependency in several cancer types. MELK RNAi and small-molecule inhibitors of MELK block the proliferation of various cancer cell lines, and MELK knockdown has been described as particularly effective against the highly-aggressive basal/triple-negative subtype of breast cancer. Based on these preclinical results, the MELK inhibitor OTS167 is currently being tested as a novel chemotherapy agent in several clinical trials. Here, we report that mutagenizing MELK with CRISPR/Cas9 has no effect on the fitness of basal breast cancer cell lines or cell lines from six other cancer types. Cells that harbor null mutations in MELK exhibit wild-type doubling times, cytokinesis, and anchorage-independent growth. Furthermore, MELK-knockout lines remain sensitive to OTS167, suggesting that this drug blocks cell division through an off-target mechanism. In total, our results undermine the rationale for a series of current clinical trials and provide an experimental approach for the use of CRISPR/Cas9 in preclinical target validation that can be broadly applied.

Emission-line galaxies in the third list of the Case Low-Dispersion Northern Sky Survey

NASA Technical Reports Server (NTRS)

Weistrop, Donna; Downes, Ronald A.

1991-01-01

Observations of 47 galaxies in the third Case list are reported. Thirty-five of the galaxies in the sample were selected for the presence of emission lines on the objective prism plates. At the higher spectral dispersion of the data, significant line emission was found in 46 of the 47 galaxies. Twenty-six galaxies are found to be undergoing significant bursts of star formation. Ten additional galaxies may be starburst galaxies with low-excitation spectra. Two galaxies are probably type Seyfert 2. The most distant object, CG 200, at a redshift of 0.144, has a strong broad H-alpha emission line, and is probably a Seyfert 1. Seventeen of the galaxies have been detected by IRAS. Eight of the IRAS galaxies have H-II-region-type spectra and eight have low-ionization starburst spectra. The galaxies represent a mixture of types, ranging from intrinsically faint dwarf galaxies with Mb equalling -16 mag, to powerful galaxies with MB equalling -23 mag. Galaxies CG 234 and CG 235 are interacting, as are galaxies CG 269 and CG 270.

Sensitivity booster for DOI-PET scanner by utilizing Compton scattering events between detector blocks

NASA Astrophysics Data System (ADS)

Yoshida, Eiji; Tashima, Hideaki; Yamaya, Taiga

2014-11-01

In a conventional PET scanner, coincidence events are measured with a limited energy window for detection of photoelectric events in order to reject Compton scatter events that occur in a patient, but Compton scatter events caused in detector crystals are also rejected. Scatter events within the patient causes scatter coincidences, but inter crystal scattering (ICS) events have useful information for determining an activity distribution. Some researchers have reported the feasibility of PET scanners based on a Compton camera for tracing ICS into the detector. However, these scanners require expensive semiconductor detectors for high-energy resolution. In the Anger-type block detector, single photons interacting with multiple detectors can be obtained for each interacting position and complete information can be gotten just as for photoelectric events in the single detector. ICS events in the single detector have been used to get coincidence, but single photons interacting with multiple detectors have not been used to get coincidence. In this work, we evaluated effect of sensitivity improvement using Compton kinetics in several types of DOI-PET scanners. The proposed method promises to improve the sensitivity using coincidence events of single photons interacting with multiple detectors, which are identified as the first interaction (FI). FI estimation accuracy can be improved to determine FI validity from the correlation between Compton scatter angles calculated on the coincidence line-of-response. We simulated an animal PET scanner consisting of 42 detectors. Each detector block consists of three types of scintillator crystals (LSO, GSO and GAGG). After the simulation, coincidence events are added as information for several depth-of-interaction (DOI) resolutions. From the simulation results, we concluded the proposed method promises to improve the sensitivity considerably when effective atomic number of a scintillator is low. Also, we showed that FI estimate accuracy is improved, as DOI resolution is high.

In vitro cytotoxic screening of selected Saudi medicinal plants.

PubMed

Almehdar, Hussein; Abdallah, Hossam M; Osman, Abdel-Moneim M; Abdel-Sattar, Essam A

2012-04-01

Many natural products from plants have been identified to exert anticancer activity. It might be expected to be a challenge to look at the Saudi plants in order to discover new sources for new molecules which may have anticancer activity. The methanolic extracts of forty species of plants traditionally used in Saudi Arabia for the treatment of a variety of diseases were tested in vitro for their potential anticancer activity on different human cancer cell lines. The cytotoxic activity of the methanolic extracts of the tested plants were determined using three human cancer cell lines, namely, breast cancer (MCF7), hepatocellular carcinoma (HEPG2), and cervix cancer (HELA) cells. In addition, human normal melanocyte (HFB4) was used as normal nonmalignant cells. Sulforhodamine B colorimetric assay was used to evaluate the in vitro cytotoxic activity of the different extracts. The growth inhibition of 50% (IC(50)) for each extract was calculated from the optical density of treated and untreated cells. Doxorubicin, a broad-spectrum anticancer drug, was used as the positive control. Nine plant extracts were chosen for further fractionation based on their activity and availability. Interesting cytotoxic activity was observed for Hypoestes forskaolii, Withania somnifera, Solanum glabratum, Adenium obesum, Pistacia vera oleoresin, Caralluma quadrangula, Eulophia petersii, Phragmanthera austroarabica, and Asparagus officinalis. Other extracts showed poor activity.

Effects of the novel anthelmintic emodepside on the locomotion, egg-laying behaviour and development of Caenorhabditis elegans.

PubMed

Bull, Kathryn; Cook, Alan; Hopper, Neil A; Harder, Achim; Holden-Dye, Lindy; Walker, Robert J

2007-05-01

Emodepside, a cyclooctadepsipeptide, is a broad-spectrum anthelmintic previously shown to paralyse body wall muscle and pharyngeal muscle in the model nematode Caenorhabditis elegans. We demonstrate that wild-type C. elegans L4 are less sensitive than adults to emodepside in two independent assays of locomotor behaviour: body bend generation on agar (adult IC(50) 3.7 nM, L4 IC(50) 13.4 nM) and thrashing behaviour in liquid (thrashing behaviour as a % of controls after 1h in 10 microM emodepside: adults 16%, L4 worms 48%). We also show that continuous exposure of wild-type C. elegans to emodepside throughout the life-cycle from egg onwards, slows worm development, an effect that is emodepside concentration-dependent. The rate of worm-hatching from eggs on agar plates containing emodepside was not significantly different from controls, suggesting that it is development post-hatching rather than hatching itself that is affected by the drug. Emodepside also inhibits wild-type C. elegans egg-laying, with acute exposure to the drug at 500 nM resulting in an almost total inhibition within the first hour. However, the rate of egg production was not inhibited and therefore emodepside-treated worms became bloated with eggs, eventually rupturing. This suggests that the effect of emodepside on reproduction is not due to an inhibition of egg production but rather a paralytic effect on the egg-laying muscles. These results, when coupled with previous research, suggest that emodepside interferes with signalling at the neuromuscular junction on the body-wall muscles (Willson et al., 2003), pharynx (Willson et al., 2004) and egg-laying muscles and thus inhibits three important physiological functions: locomotion, feeding and reproduction.

Elastic anomaly and aging of new type of incommensurate phase transition in ferroelectric barium sodium niobate

NASA Astrophysics Data System (ADS)

Christy, Yohanes; Matsumoto, Kazuya; Kojima, Seiji

2015-07-01

The lattice instability of the incommensurate (IC) phase transition of uniaxial ferroelectric Ba2NaNb5O15 (BNN) was investigated by micro-Brillouin scattering. Spectra of the longitudinal acoustic (LA) mode were observed from room temperature to 750 K. In the vicinity of the IC phase transition temperature TIC = 573 K, elastic anomalies in the form of a sharp peak in the sound velocity and thermal hysteresis during the heating and cooling cycle were observed. During this transition, the crystal point group changed from tetragonal 4mm to orthorhombic 2mm along with the IC modulation. In order to deepen our understanding of the thermal hysteresis, aging experiment in the IC phase was conducted. We can conclude that the appearance of thermal hysteresis related to the relaxation of ferroelastic strain is related to the feature of the new type III IC phase transition mechanism of BNN.

THE LICK AGN MONITORING PROJECT 2011: SPECTROSCOPIC CAMPAIGN AND EMISSION-LINE LIGHT CURVES

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

Barth, Aaron J.; Bennert, Vardha N.; Canalizo, Gabriela

2015-04-15

In the Spring of 2011 we carried out a 2.5 month reverberation mapping campaign using the 3 m Shane telescope at Lick Observatory, monitoring 15 low-redshift Seyfert 1 galaxies. This paper describes the observations, reductions and measurements, and data products from the spectroscopic campaign. The reduced spectra were fitted with a multicomponent model in order to isolate the contributions of various continuum and emission-line components. We present light curves of broad emission lines and the active galactic nucleus (AGN) continuum, and measurements of the broad Hβ line widths in mean and rms spectra. For the most highly variable AGNs wemore » also measured broad Hβ line widths and velocity centroids from the nightly spectra. In four AGNs exhibiting the highest variability amplitudes, we detect anticorrelations between broad Hβ width and luminosity, demonstrating that the broad-line region “breathes” on short timescales of days to weeks in response to continuum variations. We also find that broad Hβ velocity centroids can undergo substantial changes in response to continuum variations; in NGC 4593, the broad Hβ velocity shifted by ∼250 km s{sup −1} over a 1 month period. This reverberation-induced velocity shift effect is likely to contribute a significant source of confusion noise to binary black hole searches that use multi-epoch quasar spectroscopy to detect binary orbital motion. We also present results from simulations that examine biases that can occur in measurement of broad-line widths from rms spectra due to the contributions of continuum variations and photon-counting noise.« less

The Lick AGN Monitoring Project 2011: Spectroscopic Campaign and Emission-line Light Curves

NASA Technical Reports Server (NTRS)

Barth, Aaron J.; Bennert, Vardha N.; Canalizo, Gabriela; Filippenko, Alexei V.; Gates, Elinor L.; Greene, Jenny E..; Li, Weidong; Malkan, Matthew A.; Pancoast, Anna; Sand, David J.;

The planetary nebula IC 4776 and its post-common-envelope binary central star

NASA Astrophysics Data System (ADS)

Sowicka, Paulina; Jones, David; Corradi, Romano L. M.; Wesson, Roger; García-Rojas, Jorge; Santander-García, Miguel; Boffin, Henri M. J.; Rodríguez-Gil, Pablo

2017-11-01

We present a detailed analysis of IC 4776, a planetary nebula displaying a morphology believed to be typical of central star binarity. The nebula is shown to comprise a compact hourglass-shaped central region and a pair of precessing jet-like structures. Time-resolved spectroscopy of its central star reveals a periodic radial velocity variability consistent with a binary system. Whilst the data are insufficient to accurately determine the parameters of the binary, the most likely solutions indicate that the secondary is probably a low-mass main-sequence star. An empirical analysis of the chemical abundances in IC 4776 indicates that the common-envelope phase may have cut short the asymptotic giant branch evolution of the progenitor. Abundances calculated from recombination lines are found to be discrepant by a factor of approximately 2 relative to those calculated using collisionally excited lines, suggesting a possible correlation between low-abundance discrepancy factors and intermediate-period post-common-envelope central stars and/or Wolf-Rayet central stars. The detection of a radial velocity variability associated with the binarity of the central star of IC 4776 may be indicative of a significant population of (intermediate-period) post-common-envelope binary central stars that would be undetected by classic photometric monitoring techniques.

78 FR 54955 - Mississippi Central Railroad Co.-Lease and Change in Operators Exemption-Line of Mississippi...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-06

... Central Railroad Co.--Lease and Change in Operators Exemption--Line of Mississippi-Alabama Railroad Authority Mississippi Central Railroad Co. (MSCI), a Class III rail carrier, has filed a verified notice of exemption under 49 CFR 1150.41 to lease and operate a 41.5-mile line of railroad between milepost IC-529.5...

Selecting superluminous supernovae in faint galaxies from the first year of the Pan-STARRS1 Medium Deep Survey

NASA Astrophysics Data System (ADS)

McCrum, M.; Smartt, S. J.; Rest, A.; Smith, K.; Kotak, R.; Rodney, S. A.; Young, D. R.; Chornock, R.; Berger, E.; Foley, R. J.; Fraser, M.; Wright, D.; Scolnic, D.; Tonry, J. L.; Urata, Y.; Huang, K.; Pastorello, A.; Botticella, M. T.; Valenti, S.; Mattila, S.; Kankare, E.; Farrow, D. J.; Huber, M. E.; Stubbs, C. W.; Kirshner, R. P.; Bresolin, F.; Burgett, W. S.; Chambers, K. C.; Draper, P. W.; Flewelling, H.; Jedicke, R.; Kaiser, N.; Magnier, E. A.; Metcalfe, N.; Morgan, J. S.; Price, P. A.; Sweeney, W.; Wainscoat, R. J.; Waters, C.

2015-04-01

The Pan-STARRS1 (PS1) survey has obtained imaging in five bands (griz yP1) over 10 Medium Deep Survey (MDS) fields covering a total of 70 square degrees. This paper describes the search for apparently hostless supernovae (SNe) within the first year of PS1 MDS data with an aim of discovering superluminous supernovae (SLSNe). A total of 249 hostless transients were discovered down to a limiting magnitude of MAB ˜ 23.5, of which 76 were classified as Type Ia supernovae (SNe Ia). There were 57 SNe with complete light curves that are likely core-collapse SNe (CCSNe) or type Ic SLSNe and 12 of these have had spectra taken. Of these 12 hostless, non-Type Ia SNe, 7 were SLSNe of type Ic at redshifts between 0.5 and 1.4. This illustrates that the discovery rate of type Ic SLSNe can be maximized by concentrating on hostless transients and removing normal SNe Ia. We present data for two possible SLSNe; PS1-10pm (z = 1.206) and PS1-10ahf (z = 1.1), and estimate the rate of type Ic SLSNe to be between 3^{+3}_{-2}× 10^{-5} and 8^{+2}_{-1}× 10^{-5} that of the CCSN rate within 0.3 ≤ z ≤ 1.4 by applying a Monte Carlo technique. The rate of slowly evolving, type Ic SLSNe (such as SN2007bi) is estimated as a factor of 10 lower than this range.

The nebular spectra of the transitional Type Ia Supernovae 2007on and 2011iv: broad, multiple components indicate aspherical explosion cores

NASA Astrophysics Data System (ADS)

Mazzali, P. A.; Ashall, C.; Pian, E.; Stritzinger, M. D.; Gall, C.; Phillips, M. M.; Höflich, P.; Hsiao, E.

2018-05-01

The nebular-epoch spectrum of the rapidly declining, `transitional' Type Ia supernova (SN) 2007on showed double emission peaks, which have been interpreted as indicating that the SN was the result of the direct collision of two white dwarfs. The spectrum can be reproduced using two distinct emission components, one redshifted and one blueshifted. These components are similar in mass but have slightly different degrees of ionization. They recede from one another at a line-of-sight speed larger than the sum of the combined expansion velocities of their emitting cores, thereby acting as two independent nebulae. While this configuration appears to be consistent with the scenario of two white dwarfs colliding, it may also indicate an off-centre delayed detonation explosion of a near-Chandrasekhar-mass white dwarf. In either case, broad emission line widths and a rapidly evolving light curve can be expected for the bolometric luminosity of the SN. This is the case for both SNe 2007on and 2011iv, also a transitional SN Ia that exploded in the same elliptical galaxy, NGC 1404. Although SN 2011iv does not show double-peaked emission line profiles, the width of its emission lines is such that a two-component model yields somewhat better results than a single-component model. Most of the mass ejected is in one component, however, which suggests that SN 2011iv was the result of the off-centre ignition of a Chandrasekhar-mass white dwarf.

Identification and characterisation of mutations associated with von Willebrand disease in a Turkish patient cohort

PubMed Central

Hampshire, Daniel J.; Abuzenadah, Adel M.; Cartwright, Ashley; Al-Shammari, Nawal S.; Coyle, Rachael E.; Eckert, Michaela; Al-Buhairan, Ahlam M.; Messenger, Sarah L.; Budde, Ulrich; Gürsel, Türkiz; Ingerslev, Jørgen; Peake, Ian R.; Goodeve, Anne C.

2014-01-01

Summary Several cohort studies have investigated the molecular basis of von Willebrand disease (VWD); however these have mostly focused on European and North American populations. This study aimed to investigate mutation spectrum in 26 index cases (IC) from Turkey diagnosed with all three VWD types, the majority (73%) with parents who were knowingly related. IC were screened for mutations using multiplex ligation-dependent probe amplification and analysis of all von Willebrand factor gene (VWF) exons and exon/intron boundaries. Selected missense mutations were expressed in vitro. Candidate VWF mutations were identified in 25 of 26 IC and included propeptide missense mutations in four IC (two resulting in type 1 and two in recessive 2A), all influencing VWF expression in vitro. Four missense mutations, a nonsense mutation and a small in-frame insertion resulting in type 2A were also identified. Of 15 type 3 VWD IC, 13 were homozygous and two compound heterozygous for 14 candidate mutations predicted to result in lack of expression and two propeptide missense changes. Identification of intronic breakpoints of an exon 17–18 deletion suggested that the mutation resulted from non-homologous end joining. This study provides further insight into the pathogenesis of VWD in a population with a high degree of consanguineous partnerships. PMID:23702511

Interpretive computer simulator for the NASA Standard Spacecraft Computer-2 (NSSC-2)

NASA Technical Reports Server (NTRS)

Smith, R. S.; Noland, M. S.

1979-01-01

An Interpretive Computer Simulator (ICS) for the NASA Standard Spacecraft Computer-II (NSSC-II) was developed as a code verification and testing tool for the Annular Suspension and Pointing System (ASPS) project. The simulator is written in the higher level language PASCAL and implented on the CDC CYBER series computer system. It is supported by a metal assembler, a linkage loader for the NSSC-II, and a utility library to meet the application requirements. The architectural design of the NSSC-II is that of an IBM System/360 (S/360) and supports all but four instructions of the S/360 standard instruction set. The structural design of the ICS is described with emphasis on the design differences between it and the NSSC-II hardware. The program flow is diagrammed, with the function of each procedure being defined; the instruction implementation is discussed in broad terms; and the instruction timings used in the ICS are listed. An example of the steps required to process an assembly level language program on the ICS is included. The example illustrates the control cards necessary to assemble, load, and execute assembly language code; the sample program to to be executed; the executable load module produced by the loader; and the resulting output produced by the ICS.

Understanding drugs in breast cancer through drug sensitivity screening.

PubMed

Uhr, Katharina; Prager-van der Smissen, Wendy J C; Heine, Anouk A J; Ozturk, Bahar; Smid, Marcel; Göhlmann, Hinrich W H; Jager, Agnes; Foekens, John A; Martens, John W M

2015-01-01

With substantial numbers of breast tumors showing or acquiring treatment resistance, it is of utmost importance to develop new agents for the treatment of the disease, to know their effectiveness against breast cancer and to understand their relationships with other drugs to best assign the right drug to the right patient. To achieve this goal drug screenings on breast cancer cell lines are a promising approach. In this study a large-scale drug screening of 37 compounds was performed on a panel of 42 breast cancer cell lines representing the main breast cancer subtypes. Clustering, correlation and pathway analyses were used for data analysis. We found that compounds with a related mechanism of action had correlated IC50 values and thus grouped together when the cell lines were hierarchically clustered based on IC50 values. In total we found six clusters of drugs of which five consisted of drugs with related mode of action and one cluster with two drugs not previously connected. In total, 25 correlated and four anti-correlated drug sensitivities were revealed of which only one drug, Sirolimus, showed significantly lower IC50 values in the luminal/ERBB2 breast cancer subtype. We found expected interactions but also discovered new relationships between drugs which might have implications for cancer treatment regimens.

Phytochemical and biological evaluation of some Sargassum species from Persian Gulf

PubMed Central

Mehdinezhad, Negin; Ghannadi, Alireza; Yegdaneh, Afsaneh

2016-01-01

Sea algae are widely consumed in the world. There are several seaweeds including brown algae which are authorized for human consumption. These plants contain important phytochemical constituents and have various potential biological activities. The present study investigated the presence of phytochemical constituents and total phenolic quantity of the seaweeds Sargassum angustifolium, Sargassum oligocystum and Sargassum boveanum. Cytotoxicity of seaweeds was tested against HT-29, HeLa and MCF-7 cell lines. Antioxidant potential of these 3 Sargassum species was also analyzed. Cytotoxicity was characterized by IC50 of human cancer cell lines using sulforhodamine assay. Antioxidant activities were evaluated using 2,2-diphenyl-1- picrylhydrazil. The analysis revealed that tannins, saponins, sterols and triterpenes were the most abundant compounds in these Sargassum species while cyanogenic and cardiac glycosides were the least ones. Sargassum angustifolium had the highest content of total phenolics (0.061 mg/g) and showed the highest antioxidant activity (IC50 = 0.231). Cytotoxic results showed that all species could inhibit cell growth effectively, especially MCF-7 cell line (IC50 = 67.3, 56.9, 60.4 for S. oligocystum, S. angustifolium and S. boveanum respectively). Considerable phytochemicals and moderate cytotoxic activity of S. angustifolium, S. oligocystum and S. boveanum make them appropriate candidate for further studies and identification of their bioactive principles. PMID:27499794

Phytochemical and biological evaluation of some Sargassum species from Persian Gulf.

PubMed

Mehdinezhad, Negin; Ghannadi, Alireza; Yegdaneh, Afsaneh

2016-01-01

Sea algae are widely consumed in the world. There are several seaweeds including brown algae which are authorized for human consumption. These plants contain important phytochemical constituents and have various potential biological activities. The present study investigated the presence of phytochemical constituents and total phenolic quantity of the seaweeds Sargassum angustifolium, Sargassum oligocystum and Sargassum boveanum. Cytotoxicity of seaweeds was tested against HT-29, HeLa and MCF-7 cell lines. Antioxidant potential of these 3 Sargassum species was also analyzed. Cytotoxicity was characterized by IC50 of human cancer cell lines using sulforhodamine assay. Antioxidant activities were evaluated using 2,2-diphenyl-1- picrylhydrazil. The analysis revealed that tannins, saponins, sterols and triterpenes were the most abundant compounds in these Sargassum species while cyanogenic and cardiac glycosides were the least ones. Sargassum angustifolium had the highest content of total phenolics (0.061 mg/g) and showed the highest antioxidant activity (IC50 = 0.231). Cytotoxic results showed that all species could inhibit cell growth effectively, especially MCF-7 cell line (IC50 = 67.3, 56.9, 60.4 for S. oligocystum, S. angustifolium and S. boveanum respectively). Considerable phytochemicals and moderate cytotoxic activity of S. angustifolium, S. oligocystum and S. boveanum make them appropriate candidate for further studies and identification of their bioactive principles.

Unusual broad-line Mg II emitters among luminous galaxies in the baryon oscillation spectroscopic survey

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

Roig, Benjamin; Blanton, Michael R.; Ross, Nicholas P.

2014-02-01

Many classes of active galactic nuclei (AGNs) have been observed and recorded since the discovery of Seyfert galaxies. In this paper, we examine the sample of luminous galaxies in the Baryon Oscillation Spectroscopic Survey. We find a potentially new observational class of AGNs, one with strong and broad Mg II λ2799 line emission, but very weak emission in other normal indicators of AGN activity, such as the broad-line Hα, Hβ, and the near-ultraviolet AGN continuum, leading to an extreme ratio of broad Hα/Mg II flux relative to normal quasars. Meanwhile, these objects' narrow-line flux ratios reveal AGN narrow-line regions withmore » levels of activity consistent with the Mg II fluxes and in agreement with that of normal quasars. These AGN may represent an extreme case of the Baldwin effect, with very low continuum and high equivalent width relative to typical quasars, but their ratio of broad Mg II to broad Balmer emission remains very unusual. They may also be representative of a class of AGN where the central engine is observed indirectly with scattered light. These galaxies represent a small fraction of the total population of luminous galaxies (≅ 0.1%), but are more likely (about 3.5 times) to have AGN-like nuclear line emission properties than other luminous galaxies. Because Mg II is usually inaccessible for the population of nearby galaxies, there may exist a related population of broad-line Mg II emitters in the local universe which is currently classified as narrow-line emitters (Seyfert 2 galaxies) or low ionization nuclear emission-line regions.« less

Efficient synthesis of novel dialkyl-3-cyanopropylphosphate derivatives and evaluation of their anticholinesterase activity.

PubMed

Aouani, Iyadh; Sellami, Badreddine; Lahbib, Karima; Cavalier, Jean-François; Touil, Soufiane

2017-06-01

Based on the broad spectrum of biological activities associated with organophosphates, a novel type of this class of compounds was synthesized, bearing a nitrile group, from the sodium alkoxide-catalyzed reaction of dialkylphosphites with γ-ketonitriles at 80°C under solvent-free conditions. A reaction mechanism involving a phospha-Brook type rearrangement is proposed. Eight title compounds were investigated for their in vitro inhibitory potency and selectivity against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) using Ellman's spectrophotometric method. The synthesized derivatives exhibited mostly a moderate activity against both cholinesterases. The IC 50 values for BChE were in a smaller concentration range (5.96-23.35µM) compared to those for AChE inhibition (9.61-53.74µM). The diethyl-3-cyano-1-p-tolylpropylphosphate which displayed the higher dual inhibitory potency towards both cholinesterases could be considered as a potential candidate for developing new drugs to treat Alzheimer's disease. Copyright © 2017 Elsevier Inc. All rights reserved.

Synthesis, kinetic studies and molecular modeling of novel tacrine dimers as cholinesterase inhibitors.

PubMed

de Aquino, Roney Anderson Nascimento; Modolo, Luzia Valentina; Alves, Rosemeire Brondi; de Fátima, Ângelo

2013-12-28

This study presents the synthesis of 15 new tacrine dimers as well as the Ki and IC50 results, studies of the kinetic mechanism, and molecular docking analysis of the dimers in relation to the cholinesterases hAChE, hBChE, EeAChE and eqBChE. In addition to spectroscopic characterization, X-ray structure determination was performed for two of the new compounds. These new dimers were found to be mixed nanomolar inhibitors of the evaluated targets with a broad and significant selectivity profile, and these properties are dependent on both the type of the linker and the volume of the hydroacridine alicyclic ring. The results indicate that the aromatic linkers play a significant role in generating specific interactions with the half-gorge region of the catalytic center. Thus, these types of linkers can positively modulate the electronic properties of the tacrine dimers studied with an improvement of their cholinesterase inhibition activity.

Cancer stem cells CD133 inhibition and cytotoxicity of certain 3-phenylthiazolo[3,2-a]benzimidazoles: design, direct synthesis, crystal study and in vitro biological evaluation.

PubMed

Al-Ansary, Ghada H; Eldehna, Wagdy M; Ghabbour, Hazem A; Al-Rashood, Sara T A; Al-Rashood, Khalid A; Eladwy, Radwa A; Al-Dhfyan, Abdullah; Kabil, Maha M; Abdel-Aziz, Hatem A

2017-12-01

Cancer stem cells (CSCs) have been objects of intensive study since their identification in 1994. Adopting a structural rigidification approach, a novel series of 3-phenylthiazolo[3,2-a]benzimidazoles 4a-d was designed and synthesised, in an attempt to develop potent anticancer agent that can target the bulk of tumour cells and CSCs. The anti-proliferative activity of the synthesised compounds was evaluated against two cell lines, namely; colon cancer HT-29 and triple negative breast cancer MDA-MB-468 cell lines. Also, their inhibitory activity against the cell surface expression of CD133 was examined. In particular, compound 4b emerged as a promising hit molecule as it manifested good antineoplastic potency against both tested cell lines (IC 50  = 9 and 12 μM, respectively), beside its ability to inhibit the cell surface expression of CD133 by 50% suggesting a promising potential of effectively controlling the tumour by eradicating the tumour bulk and inhibiting the proliferation of the CSCs. Moreover, compounds 4a and 4c showed moderate activity against HT-29 (IC 50  = 21 and 29 μM, respectively) and MDA-MB-468 (IC 50  = 23 and 24 μM, respectively) cell lines, while they inhibited the CD133 expression by 14% and 48%, respectively. Finally, a single crystal X-ray diffraction was recorded for compound 4d.

Synthesis and antiproliferative activity of two diastereomeric lignan amides serving as dimeric caffeic acid-l-DOPA hybrids.

PubMed

Magoulas, George E; Rigopoulos, Andreas; Piperigkou, Zoi; Gialeli, Chrysostomi; Karamanos, Nikos K; Takis, Panteleimon G; Troganis, Anastassios N; Chrissanthopoulos, Athanassios; Maroulis, George; Papaioannou, Dionissios

2016-06-01

Two new diastereomeric lignan amides (4 and 5) serving as dimeric caffeic acid-l-DOPA hybrids were synthesized. The synthesis involved the FeCl3-mediated phenol oxidative coupling of methyl caffeate to afford trans-diester 1a as a mixture of enantiomers, protection of the catechol units, regioselective saponification, coupling with a suitably protected l-DOPA derivative, separation of the two diastereomers thus obtained by flash column chromatography and finally global chemoselective deprotection of the catechol units. The effect of hybrids 4 and 5 and related compounds on the proliferation of two breast cancer cell lines with different metastatic potential and estrogen receptor status (MDA-MB-231 and MCF-7) and of one epithelial lung cancer cell line, namely A-549, was evaluated for concentrations ranging from 1 to 256μM and periods of treatment of 24, 48 and 72h. Both hybrids showed interesting and almost equipotent antiproliferative activities (IC50 64-70μM) for the MDA-MB-231 cell line after 24-48h of treatment, but they were more selective and much more potent (IC50 4-16μM) for the MCF-7 cells after 48h of treatment. The highest activity for both hybrids and both breast cancer lines was observed after 72h of treatment (IC50 1-2μM), probably as the result of slow hydrolysis of their methyl ester functions. Copyright © 2016 Elsevier Inc. All rights reserved.

Spatial variation of the physical conditions of molecular gas in galaxies

NASA Technical Reports Server (NTRS)

Jackson, James M.; Eckart, Andreas; Wild, Wolfgang; Genzel, Reinhard; Harris, Andrew I.; Downes, Dennis; Jaffe, D. T.; Ho, Paul T. P.

1990-01-01

Multi-line studies of CO-12, CO-13, C-18O, HCN, and HCO(+) at 3 mm, 1.3 mm, and 0.8 mm using the Institute for Radio Astronomy in the Millimeter range (IRAM) 30 m telescope, with the IRAM superconductor insulator superconductor (SIS) receivers and the Max Planck Institute for External Physics (MPE) 350 GHz SIS receiver, show that the densities and temperatures of molecular gas in external galaxies change significantly with position. CO-12 measures the densities and temperature of diffuse interclump molecular gas, but not the bulk of the molecular gas. Simple one-component models, with or without external heating, cannot account for the weakness of the CO-12 J = 3 to 2 line relative to J = 2 to 1 and J = 1 to 0. CO-12 does not trace the bulk of the molecular gas, and optical depth effects obviate a straightforward interpretation of CO-12 data. Instead, researchers turned to the optically thin CO isotopes and other molecular species. Isotopic CO lines measure the bulk of the molecular gas, and HCN and HCO(+) pick out denser regions. Researchers find a warm ridge of gas in IC 342 (Eckart et al. 1989), denser gas in the starburst nucleus of IC 342, and a possible hot-spot in NGC 2903. In IC 342, NGC 2146, and NGC 6764, the CO-13 J = 2 to 1 line is subthermally populated, implying gas densities less than or equal to 10(exp 4) cm(-3).

Modulation of Induced Cytotoxicity of Doxorubicin by Using Apoferritin and Liposomal Cages

PubMed Central

Gumulec, Jaromir; Fojtu, Michaela; Raudenska, Martina; Sztalmachova, Marketa; Skotakova, Anna; Vlachova, Jana; Skalickova, Sylvie; Nejdl, Lukas; Kopel, Pavel; Knopfova, Lucia; Adam, Vojtech; Kizek, Rene; Stiborova, Marie; Babula, Petr; Masarik, Michal

2014-01-01

Doxorubicin is an effective chemotherapeutic drug, however, its toxicity is a significant limitation in therapy. Encapsulation of doxorubicin inside liposomes or ferritin cages decreases cardiotoxicity while maintaining anticancer potency. We synthesized novel apoferritin- and liposome-encapsulated forms of doxorubicin (“Apodox” and “lip-8-dox”) and compared its toxicity with doxorubicin and Myocet on prostate cell lines. Three different prostatic cell lines PNT1A, 22Rv1, and LNCaP were chosen. The toxicity of the modified doxorubicin forms was compared to conventional doxorubicin using the MTT assay, real-time cell impedance-based cell growth method (RTCA), and flow cytometry. The efficiency of doxorubicin entrapment was 56% in apoferritin cages and 42% in the liposome carrier. The accuracy of the RTCA system was verified by flow-cytometric analysis of cell viability. The doxorubicin half maximal inhibition concentrations (IC50) were determined as 170.5, 234.0, and 169.0 nM for PNT1A, 22Rv1, and LNCaP, respectively by RTCA. Lip8-dox is less toxic on the non-tumor cell line PNT1A compared to doxorubicin, while still maintaining the toxicity to tumorous cell lines similar to doxorubicin or epirubicin (IC50 = 2076.7 nM for PNT1A vs. 935.3 and 729.0 nM for 22Rv1 and LNCaP). Apodox IC50 was determined as follows: 603.1, 1344.2, and 931.2 nM for PNT1A, 22Rv1, and LNCaP. PMID:25514405

Essential Oil Content of the Rhizome of Curcuma purpurascens Bl. (Temu Tis) and Its Antiproliferative Effect on Selected Human Carcinoma Cell Lines

PubMed Central

Hong, Sok-Lai; Lee, Guan-Serm; Ahmed Hamdi, Omer Abdalla; Awang, Khalijah; Aznam Nugroho, Nurfina

2014-01-01

Curcuma purpurascens Bl., belonging to the Zingiberaceae family, is known as temu tis in Yogyakarta, Indonesia. In this study, the hydrodistilled dried ground rhizome oil was investigated for its chemical content and antiproliferative activity against selected human carcinoma cell lines (MCF7, Ca Ski, A549, HT29, and HCT116) and a normal human lung fibroblast cell line (MRC5). Results from GC-MS and GC-FID analysis of the rhizome oil of temu tis showed turmerone as the major component, followed by germacrone, ar-turmerone, germacrene-B, and curlone. The rhizome oil of temu tis exhibited strong cytotoxicity against HT29 cells (IC50 value of 4.9 ± 0.4 μg/mL), weak cytotoxicity against A549, Ca Ski, and HCT116 cells (with IC50 values of 46.3 ± 0.7, 32.5 ± 1.1, and 35.0 ± 0.3 μg/mL, resp.), and no inhibitory effect against MCF7 cells. It exhibited mild cytotoxicity against a noncancerous human lung fibroblast cell line (MRC5), with an IC50 value of 25.2 ± 2.7 μg/mL. This is the first report on the chemical composition of this rhizome's oil and its selective antiproliferative effect on HT29. The obtained data provided a basis for further investigation of the mode of cell death. PMID:25177723

Bioactive oleanane-type saponins from the rhizomes of Anemone taipaiensis.

PubMed

Wang, Xiao-Yang; Gao, Hui; Zhang, Wei; Li, Yuan; Cheng, Guang; Sun, Xiao-Li; Tang, Hai-Feng

2013-10-15

Investigation of the n-BuOH extract of the rhizomes of Anemone taipaiensis led to the isolation of five new oleanane-type triterpenoid saponins (1-5), together with seven known saponins (6-12). Their structures were determined by the extensive use of (1)D and (2)D NMR experiments along with ESIMS analyses and acid hydrolysis. The aglycone of 1, 2 and 4 was determined as siaresinolic acid, which was reported in this genus for the first time. The cytotoxicities of the saponins 1-12, prosapogenins 4a, 5a, 10a-12a and sapogenins siaresinolic acid (SA), oleanolic acid (OA), hederagenin (HE) were evaluated against five human cancer cell lines, including HepG2, HL-60, A549, HeLa and U87MG. The monodesmosidic saponins 6-8, 5a, 10a-12a and sapogenins SA, OA, HE exhibited cytotoxic activity toward all cancer cell lines, with IC50 values ranging from 2.25 to 57.28 μM. Remarkably, the bisdesmosidic saponins 1-4 and 9 showed selective cytotoxicity against the U87MG cells. Copyright © 2013 Elsevier Ltd. All rights reserved.

ASCA Observations of LMC SNRS

NASA Technical Reports Server (NTRS)

Hughes, John P.

1999-01-01

We present our first results from a study of the supernova remnants (SNRs) in the Large Magellanic Cloud (LMC) using data from ASCA. The three remnants we have analyzed to date, 0509-67.5, 0519-69.0, and N103B, are among the smallest, and presumably also the youngest, in the Cloud. The X-ray spectra of these SNRs show strong K(alpha) emission lines of silicon, sulfur, argon, and calcium with no evidence for corresponding lines of oxygen, neon, or magnesium. The dominant feature in the spectra is a broad blend of emission lines around 1 keV which we attribute to L-shell emission lines of iron. Model calculations (Nomoto, Thielemann, & Yokoi 1984) show that the major products of nucleosynthesis in Type Ia supernovae (SNs) are the elements from silicon to iron, as observed here. The calculated nucleosynthetic yields from Type Ib and II SNs are shown to be qualitatively inconsistent with the data. We conclude that the SNs which produced these remnants were of Type Ia. This finding also confirms earlier suggestions that the class of Balmer-dominated remnants arise from Type Ia SN explosions. Based an these early results from the LMC SNR sample, we find that roughly one-half of the SNRs produced in the LMC within the last approximately 1500 yr came from Type Ia SNs.

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

Huang, Z; Jiang, W; Stuart, B

Purpose: Since electrons are easily scattered, the virtual source position for electrons is expected to locate below the x-ray target of Medical Linacs. However, the effective SSD method yields the electron virtual position above the x-ray target for some applicators for some energy in Siemens Linacs. In this study, we propose to use IC Profiler (Sun Nuclear) for evaluating the electron virtual source position for the standard electron applicators for various electron energies. Methods: The profile measurements for various nominal source-to-detector distances (SDDs) of 100–115 cm were carried out for electron beam energies of 6–18 MeV. Two methods were used:more » one was to use a 0.125 cc ion chamber (PTW, Type 31010) with buildup mounted in a PTW water tank without water filled; and the other was to use IC Profiler with a buildup to achieve charge particle equilibrium. The full width at half-maximum (FWHM) method was used to determine the field sizes for the measured profiles. Backprojecting (by a straight line) the distance between the 50% points on the beam profiles for the various SDDs, yielded the virtual source position for each applicator. Results: The profiles were obtained and the field sizes were determined by FWHM. The virtual source positions were determined through backprojection of profiles for applicators (5, 10, 15, 20, 25). For instance, they were 96.415 cm (IC Profiler) vs 95.844 cm (scanning ion chamber) for 9 MeV electrons with 10×10 cm applicator and 97.160 cm vs 97.161 cm for 12 MeV electrons with 10×10 cm applicator. The differences in the virtual source positions between IC profiler and scanning ion chamber were within 1.5%. Conclusion: IC Profiler provides a practical method for determining the electron virtual source position and its results are consistent with those obtained by profiles of scanning ion chamber with buildup.« less

FIR: Efficacy, Safety, and Biomarker Analysis of a Phase II Open-Label Study of Atezolizumab in PD-L1-Selected Patients with Non-Small-Cell Lung Cancer.

PubMed

Spigel, David R; Chaft, Jamie E; Gettinger, Scott; Chao, Bo H; Dirix, Luc; Schmid, Peter; Chow, Laura Q M; Hicks, Rodney J; Leon, Larry; Fredrickson, Jill; Kowanetz, Marcin; Sandler, Alan; Funke, Roel; Rizvi, Naiyer A

2018-05-15

The FIR phase II study (NCT01846416) evaluated the efficacy and safety of anti-programmed death-ligand 1 (PD-L1) atezolizumab in advanced non-small-cell lung cancer (NSCLC) selected by tumor cell (TC) or tumor-infiltrating immune cell (IC) PD-L1 expression. Patients with PD-L1 TC2/3 (PD-L1 staining on ≥5% of TC) or IC2/3 tumors (PD-L1 staining on ≥5% of IC; determined by SP142 PD-L1 immunohistochemistry assay) with paired fresh and archival histology samples were recruited into Cohort 1 (chemotherapy-naïve/>6 months between adjuvant chemotherapy and recurrence), Cohort 2 (≥ second-line without brain metastases), or Cohort 3 (≥ second-line with treated brain metastases). Patients received 1200 mg atezolizumab, Day 1 (21-day cycles). Primary endpoint: investigator-assessed modified Response Evaluation Criteria in Solid Tumors (mRECIST), objective response rate (ORR; RECIST v1.1). Secondary endpoints: overall survival, progression-free survival, duration of response, safety. Patients (n=138) were enrolled (137 evaluable for response: Cohort 1, n=31; Cohort 2, n=93; Cohort 3, n=13). Investigator-assessed ORR was 32%, 21%, and 23% for Cohorts 1, 2, and 3, respectively. Treatment-related adverse events (TRAEs) were reported in 81%, 67%, and 69% of patients, respectively, including grade 3-4 TRAEs in 16%, 19%, and 15%. Moreover, 88.6% (n=86/97) paired baseline tumor samples had <5% change in TC/IC PD-L1 expression over time. Atezolizumab monotherapy showed clinical activity in patients with NSCLC, including those with brain metastases; safety was consistent with previous trials. Atezolizumab has completed phase III monotherapy studies in second-line; front-line trials are ongoing, confirming these favorable results. Copyright © 2018. Published by Elsevier Inc.

Lanostane-type triterpenoids from the fruiting body of Ganoderma calidophilum.

PubMed

Huang, Sheng-Zhuo; Ma, Qing-Yun; Kong, Fan-Dong; Guo, Zhi-Kai; Cai, Cai-Hong; Hu, Li-Li; Zhou, Li-Man; Wang, Qi; Dai, Hao-Fu; Mei, Wen-Li; Zhao, You-Xing

2017-11-01

To search for active anti-cancer constituents in the fruiting body of Ganoderma calidophilum, we have successfully isolated four previously undescribed spiro-lactone lanostane triterpenoids (spiroganocalitones A-D), two previously undescribed lanostanoids (ganodecalones A and B) together with twenty-three known ones. The structures of the six previously undescribed compounds were elucidated based on 1D, 2D-NMR, and HRMS analyses. Ganoderone A showed moderate cytotoxic activity against K562, BEL7402, and SGC790 cell lines with IC 50 values of 7.62, 6.28, and 3.55 μM, respectively. Copyright © 2017 Elsevier Ltd. All rights reserved.

[Value of immunologic phenotyping of acute leukemias in children].

PubMed

Vannier, J P; Bene, M C

1989-10-01

Immunologic typing has demonstrated considerable heterogeneity among the acute leukemias. The most significant recent advance has been development of monoclonal antibody techniques. Some markers identified using these techniques seem to be specific for a given stage of maturation of one lymphoid or myeloid cell line. Most acute lymphoblastic leukemias (ALLs) are malignant proliferations whose differentiation appears to have become 'stuck' at one stage of maturation. Results of immunologic typing correlate well with the other clinical and biological data. For prognostic purposes, several patterns can be identified. Among B line ALLs, four varieties have been differentiated, i.e., CD10 negative ALLs, common ALLs, pre-B ALLs, and B ALLs. T ALLs include a broad spectrum of heterogeneous proliferations whose immunologic classification is made difficult by the large number of phenotypes encountered. Among acute myeloblastic leukemias (AMLs), some highly undifferentiated forms have been recognized, by means of immunologic typing, as originating in one of the myeloid cell lines. However, the nosologic and prognostic significance of these studies is less obvious than in ALLs.

Stellar Photometric Structures of the Host Galaxies of Nearby Type 1 Active Galactic Nuclei

NASA Astrophysics Data System (ADS)

Kim, Minjin; Ho, Luis C.; Peng, Chien Y.; Barth, Aaron J.; Im, Myungshin

2017-10-01

We present detailed image analysis of rest-frame optical images of 235 low-redshift (z ≲ 0.35) Type 1 active galactic nuclei (AGNs) observed with the Hubble Space Telescope. The high-resolution images enable us to perform rigorous two-dimensional image modeling to decouple the luminous central point source from the host galaxy, which, when warranted, is further decomposed into its principal structural components (bulge, bar, and disk). In many cases, care must be taken to account for structural complexities such as spiral arms, tidal features, and overlapping or interacting companion galaxies. We employ Fourier modes to characterize the degree of asymmetry of the light distribution of the stars as a quantitative measure of morphological distortion due to interactions or mergers. We examine the dependence of the physical parameters of the host galaxies on the properties of the AGNs, namely, radio-loudness and the width of the broad emission lines. In accordance with previous studies, narrow-line (Hβ FWHM ≤ 2000 km s-1) Type 1 AGNs, in contrast to their broad-line (Hβ FWHM > 2000 km s-1) counterparts, are preferentially hosted in later-type, lower-luminosity galaxies, which have a higher incidence of pseudo-bulges, are more frequently barred, and are less morphologically disturbed. This suggests that narrow-line Type 1 AGNs experienced a more quiescent evolutionary history driven primarily by internal secular evolution instead of external dynamical perturbations. The fraction of AGN hosts showing merger signatures is larger for more luminous sources. Radio-loud AGNs generally preferentially live in earlier-type (bulge-dominated), more massive hosts, although a minority of them appear to contain a significant disk component. We do not find convincing evidence for enhanced merger signatures in the radio-loud population. Based on observations made with the NASA/ESA Hubble Space Telescope, obtained from the Data Archive at the Space Telescope Science Institute, which is operated by the Association of Universities for Research in Astronomy (AURA), Inc., under NASA contract NAS5-26555. These data are associated with program AR-12133 and AR-12818.

Human inferior colliculus activity relates to individual differences in spoken language learning.

PubMed

Chandrasekaran, Bharath; Kraus, Nina; Wong, Patrick C M

2012-03-01

A challenge to learning words of a foreign language is encoding nonnative phonemes, a process typically attributed to cortical circuitry. Using multimodal imaging methods [functional magnetic resonance imaging-adaptation (fMRI-A) and auditory brain stem responses (ABR)], we examined the extent to which pretraining pitch encoding in the inferior colliculus (IC), a primary midbrain structure, related to individual variability in learning to successfully use nonnative pitch patterns to distinguish words in American English-speaking adults. fMRI-A indexed the efficiency of pitch representation localized to the IC, whereas ABR quantified midbrain pitch-related activity with millisecond precision. In line with neural "sharpening" models, we found that efficient IC pitch pattern representation (indexed by fMRI) related to superior neural representation of pitch patterns (indexed by ABR), and consequently more successful word learning following sound-to-meaning training. Our results establish a critical role for the IC in speech-sound representation, consistent with the established role for the IC in the representation of communication signals in other animal models.

On the variations of O III forbidden line intensities in the spectrum of the planetary nebula IC 4997

NASA Astrophysics Data System (ADS)

Egikyan, A. G.

1997-10-01

The causes of asynchronous variations in the intensities of forbidden O III lines in the spectrum of the planetary nebula IC 4997 are considered. It is shown that the strengthening of the 4363-A line with a simultaneous weakening of the N1 and N2 lines can be explained by a severalfold increase of the mass-loss rate from the nucleus, up to 1-2 x 10 exp -7 solar mass/yr, over several years. The ionization model of the nebula under the combined effect of nucleus emission and the emission from a variable hot stellar wind with electron temperature of 500,000 K is used to calculate the theoretical line intensities. The calculations included 12 levels of O III. In the region of O III line formation, the electron density of 10 exp 6/cu cm and Te, which varies from 12,000 to 15,000 K, yield theoretical line intensities that are in best agreement with observations. The X-ray luminosity of the stellar wind from the nucleus at energies not less than 0.2 keV is on the order of 10 exp 35 erg/s, but the interstellar extinction rules out the possibility of observing this object.

IC 5181: An S0 Galaxy with Ionized Gas on Polar Orbits

NASA Astrophysics Data System (ADS)

Pizzella, A.; Morelli, L.; Corsini, E. M.; Dalla Bontá, E.; Cesetti, M.

2014-05-01

The nearby S0 galaxy IC 5181 is studied to address the origin of the ionized gas component that orbits the galaxy on polar orbit. We perform detailed photometric and spectroscopic observations measuring the surface brightness distribution of the stars (I band), ionized gas of IC 5181 (Hα narrow band), the ionized-gas and stellar kinematics along both the major and minor axis, and the corresponding line strengths of the Lick indices. We conclude that the galaxy hosts a geometrically and kinematically decoupled component of ionized gas. It is elongated along the galaxy minor axis and in orthogonal rotation with respect to the galaxy disk. The result is suggesting that the gas component is not related to the stars having an external origin. The gas was accreted by IC 5181 on polar orbits from the surrounding environment.

Benzo[g]quinazolin-based scaffold derivatives as dual EGFR/HER2 inhibitors.

PubMed

Ghorab, Mostafa M; Alsaid, Mansour S; Soliman, Aiten M; Al-Mishari, Abdullah A

2018-12-01

Targeting EGFR has proven to be beneficial in the treatment of several types of solid tumours. So, a series of novel 2-(4-oxo-3-(4-sulfamoylphenyl)-3,4-dihydrobenzo[g]quinazolin-2-ylthio)-N-substituted acetamide 5-19 were synthesised from the starting material 4-(2-mercapto-4-oxobenzo[g]quinazolin-3(4H)-yl) benzenesulfonamide 4, to be evaluated as dual EGFR/HER2 inhibitors. The target compounds 5-19, were screened for their cytotoxic activity against A549 lung cancer cell line. The percentage inhibition of EGFR enzyme was measured and compared with erlotinib as the reference drug. Compounds 6, 8, 10, and 16 showed excellent EGFR inhibitory activity and were further selected for screening as dual EGFR/HER2 inhibitors. The four selected compounds showed IC 50 ranging from 0.009 to 0.026 µM for EGFR and 0.021 to 0.069 µM for the HER2 enzyme. Compound 8 was found to be the most potent in this study with IC 50 0.009 and 0.021 µM for EGFR and HER2, respectively.

Crystallographic Orientation Effect on Electromigration in Ni-Sn Microbump

NASA Astrophysics Data System (ADS)

Huang, Yi-Ting; Chen, Chih-Hao; Chakroborty, Subhendu; Wu, Albert T.

2017-09-01

This article addresses the reliability challenges regarding electromigration in developing three-dimensional integrated circuits (3D-ICs). The line-type sandwich structure of Ni/Sn3.5Ag(15 μm)/Ni was used to simulate microbumps to examine the reliability of electromigration in 3D-IC technology. The solder strip of Ni/Sn3.5Ag(15 μm)/Ni was stressed with a current density of 1.0 × 104 A/cm2 at 150°C. The current stressing enhanced the reaction between the solder and Ni to form Ni3Sn4, which occupied the entire joint and transformed into a Ni/Ni3Sn4/Ni structure when the solder was completely consumed. Electron backscatter diffraction was used to analyze the crystallographic characteristics of Sn and Ni3Sn4 as related to the electromigration effect. The results indicated that the crystallographic orientation of Sn plays a significant role in the Ni/Sn3.5Ag/Ni, whereas the orientation of Ni3Sn4 is the dominant factor of diffusion behavior in the Ni/Ni3Sn4/Ni.

High prevalence of human papillomavirus type 58 in Mexican colposcopy patients.

PubMed

González-Losa, Maria del Refugio; Rosado-Lopez, Iván; Valdez-González, Nina; Puerto-Solís, Marylín

2004-03-01

Cervical cancer is the second most common cancer of the women worldwide. Infection with some genotypes of human papillomavirus is the most important risk factor associated to cervical cancer. To determine the prevalence and genotypes of papillomavirus in biopsies of women with squamous intraepithelial lesion and cervical cancer. Two hundred sequential patients of colposcopy clinic were studied. HPV diagnosis was done by polymerase chain reaction using MY09/MY11 primers, for genotyping line blot hybridization was used. A total of 186 women were beta globin positive; 104 (55.9%) had histology diagnosis of low-grade squamous intraepitelial lesions (LSIL), 67 (36.0%) high-grade squamous intraepitelial lesions (HSIL) and 15 (8.1%) invasive cervical cancer (IC). The prevalence of HPV was 56.4% (104/185); HPV 58 was founded in 28.5% of all positive women, HPV 16 in 25.7%, HPV 18 in 13.3%, HPV 33 in 11.4% and 31 in 8.5%. In all grades of the lesions HPV 58 was the most frequently. The high prevalence of HPV 58 among Mexican women with HSIL and IC, has important implications in prophylaxis.

Highly ionized gas absorption in the disk and halo toward HD 167756 at 3.5 kilometers per second resolution

NASA Technical Reports Server (NTRS)

Savage, Blair D.; Sembach, Kenneth R.; Cardelli, Jason A.

1994-01-01

High-resolution spectra of interstellar Si IV, C IV, and N V absorption lines along the 4 kpc path to the inner Galaxy star HD 167756 at z = -0.85 kpc are presented. The spectra were obtained with the echelle mode of Goddard High Resolution Spectrograph (GHRS) aboard the Hubble Space Telescope (HST) and have signal-to-noise ratios ranging from 23 to 38. The high resolution of the measurements full width at half maximum (FWHM = 3.5 km/s) results in fully resolved line profiles for the highly ionized gas absorption. The measurements provide information on the column density per unit velocity, N(v), as a function of velocity for Si IV, C IV, and N V. The C IV and N V profiles extend from -70 to +70 km/s, while the Si IV profiles extend from -40 to +70 km/s. The integrated logarithmic column densities are long N(Si IV) = 13.09 +/- 0.02, log N(C IV) = 13.83 +/- 0.02, and log N(N V) = 13.56 +/- 0.03. The N V profile is broad, asymmetric, and featureless, while the Si IV profile contains narrow absorption components near V(sub LSR) = -19, 0, +20, and +52 km/s with Doppler spread parameters, b about = 10-12 km/s. The C IV profile contains both broad and narrow structure. The high ion feature near +52 km/s is also detected in the low-ionization lines of Ca II, O I, Si II, and Fe II. The other narrow Si IV and C IV components occur within several km/s of components seen in low-ionization species. The sight line contains at least two types of highly ionized gas. One type gives rise to a broad N V profile, and the other results in the more structured Si IV profile. The C IV profile contains contributions from both types of highly ionized gas. The broad but asymmetric N V profile is well represented by a large Galactic scale height gas which is participating in Galactic rotation and has a combination of thermal and turbulent broadening with b(sub tot) about = 42 km/s. The C IV to N V abundance ratio of 1.0 +/- 0.3 for the gas implies T about 1.6 x 10(exp 5) K or about 8 x 10(exp 5) K if the gas is in collisional ionization equilibrium and has a solar carbon to nitrogen abundance ratio. This absorption may be associated with cooling hot gas situated in Galactic shells and supershells along the sight line. The gas producing the narrow Si IV and C IV absorption components has line widths that are compatible with origins in conductive interfaces between the warm and hot interstellar medium. Kinematic flows associated with the photoionized edges of clouds might also produce Si IV and C IV lines with Doppler spread parameters similar to those observed, but the C IV to Si IV ratio in this gas is 3.5, which leads us to favor the conductive interface interpretation.

The Suzaku Observation of NGC 3516: Complex Absorption and the Broad and Narrow Fe K Lines

NASA Technical Reports Server (NTRS)

Markowitz, Alex; Reeves, James N.; Miniutti, Giovanni; Serlemitsos, Peter; Kunieda, Hideyo; Taqoob, Tahir; Fabian, Andrew C.; Fukazawa, Yasushi; Mushotzky, Richard; Okajima, Takashi;

Methods of the pharmacological imaging of the cannabinoid system (PhICS) study: towards understanding the role of the brain endocannabinoid system in human cognition.

PubMed

van Hell, Hendrika H; Bossong, Matthijs G; Jager, Gerry; Kahn, René S; Ramsey, Nick F

2011-03-01

Various lines of (pre)clinical research indicate that cannabinoid agents carry the potential for therapeutic application to reduce symptoms in several psychiatric disorders. However, direct testing of the involvement of cannabinoid brain systems in psychiatric syndromes is essential for further development. In the Pharmacological Imaging of the Cannabinoid System (PhICS) study, the involvement of the endocannabinoid system in cognitive brain function is assessed by comparing acute effects of the cannabinoid agonist Δ9-tetrahydrocannabinol (THC) on brain function between healthy controls and groups of psychiatric patients showing cognitive dysfunction. This article describes the objectives and methods of the PhICS study and presents preliminary results of the administration procedure on subjective and neurophysiological parameters. Core elements in the methodology of PhICS are the administration method (THC is administered by inhalation using a vaporizing device) and a comprehensive use of pharmacological magnetic resonance imaging (phMRI) combining several types of MRI scans including functional MRI (fMRI), Arterial Spin Labeling (ASL) to measure brain perfusion, and resting-state fMRI. Additional methods like neuropsychological testing further specify the exact role of the endocannabinoid system in regulating cognition. Preliminary results presented in this paper indicate robust behavioral and subjective effects of THC. In addition, fMRI paradigms demonstrate activation of expected networks of brain regions in the cognitive domains of interest. The presented administration and assessment protocol provides a basis for further research on the involvement of the endocannabionoid systems in behavior and in psychopathology, which in turn may lead to development of therapeutic opportunities of cannabinoid ligands. Copyright © 2011 John Wiley & Sons, Ltd.

Acetonic Extract of Buxus sempervirens Induces Cell Cycle Arrest, Apoptosis and Autophagy in Breast Cancer Cells

PubMed Central

Ait-Mohamed, Ouardia; Battisti, Valentine; Joliot, Véronique; Fritsch, Lauriane; Pontis, Julien; Medjkane, Souhila; Redeuilh, Catherine; Lamouri, Aazdine; Fahy, Christine; Rholam, Mohamed; Atmani, Djebbar; Ait-Si-Ali, Slimane

2011-01-01

Plants are an invaluable source of potential new anti-cancer drugs. Here, we investigated the cytotoxic activity of the acetonic extract of Buxus sempervirens on five breast cancer cell lines, MCF7, MCF10CA1a and T47D, three aggressive triple positive breast cancer cell lines, and BT-20 and MDA-MB-435, which are triple negative breast cancer cell lines. As a control, MCF10A, a spontaneously immortalized but non-tumoral cell line has been used. The acetonic extract of Buxus sempervirens showed cytotoxic activity towards all the five studied breast cancer cell lines with an IC50 ranging from 7.74 µg/ml to 12.5 µg/ml. Most importantly, the plant extract was less toxic towards MCF10A with an IC50 of 19.24 µg/ml. Fluorescence-activated cell sorting (FACS) analysis showed that the plant extract induced cell death and cell cycle arrest in G0/G1 phase in MCF7, T47D, MCF10CA1a and BT-20 cell lines, concomitant to cyclin D1 downregulation. Application of MCF7 and MCF10CA1a respective IC50 did not show such effects on the control cell line MCF10A. Propidium iodide/Annexin V double staining revealed a pre-apoptotic cell population with extract-treated MCF10CA1a, T47D and BT-20 cells. Transmission electron microscopy analyses indicated the occurrence of autophagy in MCF7 and MCF10CA1a cell lines. Immunofluorescence and Western blot assays confirmed the processing of microtubule-associated protein LC3 in the treated cancer cells. Moreover, we have demonstrated the upregulation of Beclin-1 in these cell lines and downregulation of Survivin and p21. Also, Caspase-3 detection in treated BT-20 and T47D confirmed the occurrence of apoptosis in these cells. Our findings indicate that Buxus sempervirens extract exhibit promising anti-cancer activity by triggering both autophagic cell death and apoptosis, suggesting that this plant may contain potential anti-cancer agents for single or combinatory cancer therapy against breast cancer. PMID:21935420

Measuring the ISM Content of Optically Luminous Type 2 Quasars

NASA Astrophysics Data System (ADS)

Marshall, Jameeka; Petric, Andreea; Flagey, Nicolas; Lacy, Mark; Omont, Alain

2018-01-01

There is a connection between black holes (BH) and the surrounding bulge stars. Measuring the cold interstellar medium (ISM) content of host galaxies is essential to understand the coevolution of galaxies and BHs. The ISM measurement is important because gas constitutes the raw material from which BHs grow and stars form. Quasars are extremely luminous active galaxies fueled by accreting supermassive black holes. Type 2 quasars have narrow spectral lines whereas type 1 quasars have broad spectral lines. Not only can the ISM measurements provide empirical data to help further clarify quasar models but it is also crucial in distinguishing the physical differences between type 1 and type 2 quasars. Observations of twenty type 2 quasars were made using IRAM, a single dish 30 meter radio telescope, to measure 12CO (1-0) and 12CO (2-1) emission. We used line widths to constrain the dynamical mass and gravitational potential of the host galaxy. Star formation rate (SFR) measured in the infrared (IR) and SFR derived from optical spectra were used to estimate star formation efficiency and gas depletion time scale (M H2/star formation rate). Preliminary analysis suggests that star formation efficiency in type 2 quasars is slightly higher than in type 1 quasars.

Bank Vole Prion Protein As an Apparently Universal Substrate for RT-QuIC-Based Detection and Discrimination of Prion Strains.

PubMed

Orrú, Christina D; Groveman, Bradley R; Raymond, Lynne D; Hughson, Andrew G; Nonno, Romolo; Zou, Wenquan; Ghetti, Bernardino; Gambetti, Pierluigi; Caughey, Byron

2015-06-01

Prions propagate as multiple strains in a wide variety of mammalian species. The detection of all such strains by a single ultrasensitive assay such as Real Time Quaking-induced Conversion (RT-QuIC) would facilitate prion disease diagnosis, surveillance and research. Previous studies have shown that bank voles, and transgenic mice expressing bank vole prion protein, are susceptible to most, if not all, types of prions. Here we show that bacterially expressed recombinant bank vole prion protein (residues 23-230) is an effective substrate for the sensitive RT-QuIC detection of all of the different prion types that we have tested so far--a total of 28 from humans, cattle, sheep, cervids and rodents, including several that have previously been undetectable by RT-QuIC or Protein Misfolding Cyclic Amplification. Furthermore, comparison of the relative abilities of different prions to seed positive RT-QuIC reactions with bank vole and not other recombinant prion proteins allowed discrimination of prion strains such as classical and atypical L-type bovine spongiform encephalopathy, classical and atypical Nor98 scrapie in sheep, and sporadic and variant Creutzfeldt-Jakob disease in humans. Comparison of protease-resistant RT-QuIC conversion products also aided strain discrimination and suggested the existence of several distinct classes of prion templates among the many strains tested.

IC 4663: The First Unambiguous [WN] Wolf-Rayet Central Star of a Planetary Nebula

NASA Astrophysics Data System (ADS)

Miszalski, B.; Crowther, P. A.; De Marco, O.; Köppen, J.; Moffat, A. F. J.; Acker, A.; Hillwig, T. C.

2013-01-01

Several [WC]-type central stars of planetary nebulae (PNe) are known to mimic the spectroscopic appearance of massive carbon-rich or WC-type Wolf-Rayet stars. In stark contrast, no [WN]-type central stars have yet been identified as clear-cut analogues of the common nitrogen-rich or WN-type Wolf-Rayet stars. We have identified the [WN3] central star of IC 4663 to be the first unambiguous example in PNe. The low luminosity nucleus and an asymptotic giant branch (AGB) halo surrounding the main nebula prove the bona-fide PN nature of IC 4663. Model atmosphere analysis reveals the [WN3] star to have an exotic chemical composition of helium (95%), hydrogen (<2%), nitrogen (0.8%), neon (0.2%) and oxygen (0.05%) by mass. Such an extreme helium-dominated composition cannot be predicted by current evolutionary scenarios for hydrogen deficient [WC]-type central stars. Only with the discovery of IC 4663 and its unusual composition can we now connect [WN] central stars to the O(He) central stars in a second H-deficient and He-rich evolutionary sequence, [WN]→O(He), that exists in parallel to the carbon-rich [WC]→PG1159 sequence. This suggests a simpler mechanism, perhaps a binary merger, can better explain H-deficiency in PNe and potentially other H-deficient/He-rich stars. In this respect IC 4663 is the best supported case for a possible merged binary central star of a PN.

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

Horesh, Assaf; Kulkarni, Shrinivas R.; Corsi, Alessandra

Only a few cases of Type Ic supernovae (SNe) with high-velocity ejecta (≥0.2 c) have been discovered and studied. Here, we present our analysis of radio and X-ray observations of the Type Ic SN PTF 12gzk. The radio emission declined less than 10 days after explosion, suggesting SN ejecta expanding at high velocity (∼0.3 c). The radio data also indicate that the density of the circumstellar material (CSM) around the supernova is lower by a factor of ∼10 than the CSM around normal Type Ic SNe. PTF 12gzk may therefore be an intermediate event between a 'normal' SN Ic andmore » a gamma-ray-burst-SN-like event. Our observations of this rapidly declining radio SN at a distance of 58 Mpc demonstrates the potential to detect many additional radio SNe, given the new capabilities of the Very Large Array (improved sensitivity and dynamic scheduling), which are currently missed, leading to a biased view of radio SNe Ic. Early optical discovery followed by rapid radio observations would provide a full description of the ejecta velocity distribution and CSM densities around stripped massive star explosions as well as strong clues about the nature of their progenitor stars.« less

Repair of DNA double-strand breaks and cell killing by charged particles

NASA Astrophysics Data System (ADS)

Eguchi-Kasai, K.; Murakami, M.; Itsukaichi, H.; Fukutsu, K.; Yatagai, F.; Kanai, T.; Ohara, H.; Sato, K.

It has been suggested that it is not simple double-strand breaks (dsb) but the non-reparable breaks which correlate well with the high biological effectiveness of high LET radiations for cell killing. We have compared the effects of charged particles on cell death in 3 pairs of cell lines which are normal or defective in the repair of DNA dsbs. For the cell lines SL3-147, M10, and SX10 which are deficient in DNA dsb repair, RBE values were close to unity for cell killing induced by charged particles with linear energy transfer (LET) up to 200 keV/mum and were even smaller than unity for the LET region greater than 300 keV/mum. The inactivation cross section (ICS) increased with LET for all 3 pairs. The ICS of dsb repair deficient mutants was always larger than that of their parents for all the LET ranges, but with increasing LET the difference in ICS between the mutant and its parent became smaller. Since a small difference in ICS remained at LET of about 300 keV/mum, dsb repair may still take place at this high LET, even if its role is apparently small. These results suggest that the DNA repair system does not play a major role in protection against the attack of high LET radiations and that a main cause of cell death is non-reparable dsb which are produced at a higher yield compared with low LET radiations. No correlation was observed between DNA content or nuclear area and ICS.

Evaluation of antioxidant, in vitro cytotoxicity of micropropagated and naturally grown plants of Leptadenia reticulata (Retz.) Wight & Arn.-an endangered medicinal plant.

PubMed

Mohanty, Sudipta Kumar; Malappa, Kumaraswamy; Godavarthi, Ashok; Subbanarasiman, Balasubramanya; Maniyam, Anuradha

2014-09-01

To evaluate the antioxidant and anti proliferative potential of different solvent extract of micropropagated and naturally grown plants of Leptadenia reticulata against various cancer cell lines. In this study different extract were tested for cytotoxicity against human breast adenocarcinoma cell line MCF-7, human colon adenocarcinoma grade II cell line HT-29 and non cancer skeletal muscle cell line L6 through 3-(4, 5-dimethyl thiazol-2-yl)-5-diphenyl tetrazolium bromide assay. The total antioxidant potential was estimated by three different antioxidant model diphenylpicrylhydrazyl free radical scavenging activity, H2O2 scavenging activity and FeCl3 reducing activity. The ethyl acetate extract of both naturally grown plant and tissue cultured plant exhibited significant cytotoxicity with IC50 values of 21 µg/mL, 26 µg/mL and 22 µg/mL; 20 µg/mL, 30 µg/mL and 18 µg/mL respectively against three cell lines. The diphenylpicrylhydrazyl free radical scavenging activity was found to be highest with IC50 value of 267.13 µg/mL in ethyl acetate extract. The methanolic extract exhibited moderate antioxidant activity with IC50 value of 510.15 µg/mL. A highly positive correlation was observed between the antioxidant potential and cytotoxic activity of the plant. The strong cytotoxicity of ethyl acetate extract revealed anti carcinogenic potential of the plant which supports its traditional use as medicine. The present investigation is new to literature till date and will provide better scientific basis for future pharmacological, in vivo studies and novel source of pure bioactive compounds having anti cancer properties in this plant. Copyright © 2014 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

Synthesis and Anticancer Activity of Epipolythiodiketopiperazine Alkaloids

PubMed Central

Boyer, Nicolas; Morrison, Karen C.; Kim, Justin; Hergenrother, Paul J.; Movassaghi, Mohammad

2013-01-01

The epipolythiodiketopiperazine (ETP) alkaloids are a highly complex class of natural products with potent anticancer activity. Herein, we report the application of a flexible and scalable synthesis, allowing the construction of dozens of ETP derivatives. The evaluation of these compounds against cancer cell lines in culture allows for the first expansive structure–activity relationship (SAR) to be defined for monomeric and dimeric ETP-containing natural products and their synthetic cognates. Many ETP derivatives demonstrate potent anticancer activity across a broad range of cancer cell lines, and kill cancer cellsviainduction of apoptosis. Several traits thatbode well for the translational potential of the ETP class of natural products includeconcise and efficient synthetic access, potent induction of apoptotic cell death, activity against a wide range of cancer types, and a broad tolerance for modifications at multiple sitesthat should facilitate small-molecule drug development, mechanistic studies, and evaluation in vivo. PMID:23914293

CheckMate 141: 1-Year Update and Subgroup Analysis of Nivolumab as First-Line Therapy in Patients with Recurrent/Metastatic Head and Neck Cancer.

PubMed

Gillison, Maura L; Blumenschein, George; Fayette, Jerome; Guigay, Joel; Colevas, A Dimitrios; Licitra, Lisa; Harrington, Kevin J; Kasper, Stefan; Vokes, Everett E; Even, Caroline; Worden, Francis; Saba, Nabil F; Iglesias Docampo, Lara Carmen; Haddad, Robert; Rordorf, Tamara; Kiyota, Naomi; Tahara, Makoto; Monga, Manish; Lynch, Mark; Li, Li; Ferris, Robert L

2018-06-04

Nivolumab significantly improved overall survival (OS) vs investigator's choice (IC) of chemotherapy at the primary analysis of randomized, open-label, phase 3 CheckMate 141 in patients with recurrent or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN). Here, we report that OS benefit with nivolumab was maintained at a minimum follow-up of 11.4 months. Further, OS benefit with nivolumab vs IC was also noted among patients who received first-line treatment for R/M SCCHN after progressing on platinum therapy for locally advanced disease in the adjuvant or primary (i.e., with radiation) setting. The Oncologist 2018. © AlphaMed Press 2018.

Block of high-threshold calcium channels by the synthetic polyamines sFTX-3.3 and FTX-3.3.

PubMed

Norris, T M; Moya, E; Blagbrough, I S; Adams, M E

1996-10-01

A polyamine component of Agelenopsis aperta spider venom designated FTX is reported to be a selective antagonist of P-type calcium channels in the mammalian brain. Consequently, this component has frequently been used as a pharmacological tool to determine the presence, distribution, and function of P-type channels in physiological systems. We describe antagonism of calcium channels by the synthesized polyamine FTX-3.3, which has the proposed structure of natural FTX. We also examined a corresponding polyamine amide, sFTX-3.3. These polyamines are critically evaluated for antagonism of three high-threshold calcium channel subtypes in rat neurons through the use of the whole-cell patch-clamp technique. FTX-3.3 (IC50 = approximately 0.13 mM) is approximately twice as potent as sFTX-3.3 (IC50 = approximately 0.24 mM) against P-type channels and approximately 3-fold more potent against N-type channels (FTX-3.3, IC50 = approximately 0.24 mM; sFTX-3.3, IC50 = approximately 0.70 mM). Both polyamines also block L-type calcium channels with similar potencies. sFTX-3.3 (1 mM) and FTX-3.3 (0.5 mM) typically block 50% and 65% of Bay K8644-enhanced L-type current, respectively. Antagonism of each calcium channel subtype is voltage dependent, with less inhibition of Ba2+ currents at more-positive potentials. These data show that both sFTX-3.3 and FTX-3.3 antagonize P-, N-, and L-type calcium channels in mammalian Purkinje and superior cervical ganglia neurons with similar IC50 values.

ASCA observations of the Large Magellanic Cloud supernova remnant sample: Typing supernovae from their remnants

NASA Technical Reports Server (NTRS)

Hughes, John P.; Hayashi, Ichizo; Helfand, David; Hwang, Una; Itoh, Masayuki; Kirshner, Robert; Koyama, Katsuji; Markert, Thomas; Tsunemi, Hiroshi; Woo, Jonathan

1995-01-01

We present our first results from a study of the supernova remnants (SNRs) in the Large Magellanic Cloud (LMC) using data from ASCA. The three remnants we have analyzed to date, 0509-67.5, 0519-69.0, and N103B, are among the smallest, and presumably also the youngest, in the Cloud. The X-ray spectra of these SNRs show strong K alpha emission lines of silicon, sulfur, argon, and calcium with no evidence for corresponding lines of oxygen, neon, or magnesium. The dominant feature in the spectra is a broad blend of emission lines around 1 keV which we attribute to L-shell emission lines of iron. Model calculations (Nomoto, Thielemann, & Yokoi 1984) show that the major products of nucleosynthesis in Type Ia supernovae (SNs) are the elements from silicon to iron, as observed here. The calculated nucleosynthetic yields from Type Ib and II SNs are shown to be qualitatively inconsistent with the data. We conclude that the SNs which produced these remnants were of Type Ia. This finding also confirms earlier suggestions that the class of Balmer-dominated remnants arise from Type Ia SN explosions. Based on these early results from the LMC SNR sample, we find that roughly one-half of the SNRs produced in the LMC within the last approximately 1500 yr came from Type Ia SNs.

Multiple applications of ion chromatography oligosaccharide fingerprint profiles to solve a variety of sugar and sugar-biofuel industry problems

USDA-ARS?s Scientific Manuscript database

Sugar crops contain a broad variety of carbohydrates used for human consumption and the production of biofuels and bioproducts. Ion chromatography with integrated pulsed amperometric detection (IC-IPAD), also known as high performance anion exchange chromatography (HPAEC), can be used to simultaneo...

Synthesis and evaluation of new benzodioxole-based dithiocarbamate derivatives as potential anticancer agents and hCA-I and hCA-II inhibitors.

PubMed

Altıntop, Mehlika Dilek; Sever, Belgin; Akalın Çiftçi, Gülşen; Kucukoglu, Kaan; Özdemir, Ahmet; Soleimani, Seyedeh Sara; Nadaroglu, Hayrunnisa; Kaplancıklı, Zafer Asım

2017-01-05

In the current work, new benzodioxole-based dithiocarbamate derivatives were synthesized via the reaction of N-(1,3-benzodioxol-5-ylmethyl)-2-chloroacetamide with appropriate sodium salts of N,N-disubstituted dithiocarbamic acids. These derivatives were evaluated for their cytotoxic effects on A549 human lung adenocarcinoma and C6 rat glioma cell lines. N-(1,3-Benzodioxol-5-ylmethyl)-2-[4-(4-nitrophenyl)-1-piperazinylthiocarbamoylthio]acetamide (10) can be identified as the most promising anticancer agent against C6 cell line due to its notable inhibitory effect on C6 cells with an IC 50 value of 23.33 ± 7.63 μg/mL when compared with cisplatin (IC 50  = 19.00 ± 5.29 μg/mL). On the other hand, compound 10 did not show any significant cytotoxic activity against A549 cell line. The compounds were also tested for their in vitro inhibitory effects on hCA-I and hCA-II. Generally, the tested compounds were more effective on CAs than acetazolamide, the reference agent. Among these compounds, N-(1,3-benzodioxol-5-ylmethyl)-2-[(morpholinyl)thiocarbamoylthio]acetamide (3) and N-(1,3-benzodioxol-5-ylmethyl)-2-[(thiomorpholinyl)thiocarbamoylthio]acetamide (4) were found to be the most effective compounds on hCA-I with IC 50 values of 0.346 nM and 0.288 nM, and hCA-II with IC 50 values of 0.287 nM and 0.338 nM, respectively. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Production of a broad-specificity monoclonal antibody and application as a receptor to detection amatoxins in mushroom.

PubMed

He, Kuo; Mao, Qingwen; Zang, Xiuyuan; Zhang, Yanyu; Li, Hui; Zhang, Donghao

2017-09-01

In this study, we report the production of a monoclonal broad-specificity monoclonal antibody (mAb) specific for amatoxins and development of an indirect competitive immunoassay for detection of amatoxins in mushroom samples. In the assay, the complete antigen (α-amanitin-OVA) was used as coating antigen, and amatoxins as competitor competes with coating antigen to bind with mAb. Using this approach, The half-maximum inhibition concentrations (IC 50 ) of α-amanitin, β-amanitin and γ-amanitin, and limits of detection (LODs, IC 15 ) were 66.3, 97.4, 163.1 ng/mL and 0.91, 0.98, 0.89 ng/mL, respectively. The LODs for α-amanitin, β-amanitin and γ-amanitin in mushroom samples were 4.55, 4.9, and 4.45 ng/mL. The spiked results were also confirmed by HPLC, which showed a good correlation (R 2  = 0.996) between the two methods. The results indicated that the developed assay was reliable and suitable for the detection of amatoxins in mushroom samples. Copyright © 2017. Published by Elsevier Ltd.

Towards a better understanding of the evolution of Wolf-Rayet stars and Type Ib/Ic supernova progenitors

NASA Astrophysics Data System (ADS)

Yoon, Sung-Chul

2017-10-01

Hydrogen-deficient Wolf-Rayet (WR) stars are potential candidates of Type Ib/Ic supernova (SN Ib/Ic) progenitors and their evolution is governed by mass-loss. Stellar evolution models with the most popular prescription for WR mass-loss rates given by Nugis & Lamers have difficulties in explaining the luminosity distribution of WR stars of WC and WO types and the SN Ic progenitor properties. Here, we suggest some improvements in the WR mass-loss rate prescription and discuss its implications for the evolution of WR stars and SN Ib/Ic progenitors. Recent studies on Galactic WR stars clearly indicate that the mass-loss rates of WC stars are systematically higher than those of WNE stars for a given luminosity. The luminosity and initial metallicity dependences of WNE mass-loss rates are also significantly different from those of WC stars. These factors have not been adequately considered together in previous stellar evolution models. We also find that an overall increase of WR mass-loss rates by about 60 per cent compared to the empirical values obtained with a clumping factor of 10 is needed to explain the most faint WC/WO stars. This moderate increase with our new WR mass-loss rate prescription results in SN Ib/Ic progenitor models more consistent with observations than those given by the Nugis & Lamers prescription. In particular, our new models predict that the properties of SN Ib and SN Ic progenitors are distinctively different, rather than they form a continuous sequence.

Novel Bacterial Topoisomerase Inhibitors with Potent Broad-Spectrum Activity against Drug-Resistant Bacteria.

PubMed

Charrier, Cédric; Salisbury, Anne-Marie; Savage, Victoria J; Duffy, Thomas; Moyo, Emmanuel; Chaffer-Malam, Nathan; Ooi, Nicola; Newman, Rebecca; Cheung, Jonathan; Metzger, Richard; McGarry, David; Pichowicz, Mark; Sigerson, Ralph; Cooper, Ian R; Nelson, Gary; Butler, Hayley S; Craighead, Mark; Ratcliffe, Andrew J; Best, Stuart A; Stokes, Neil R

2017-05-01

The novel bacterial topoisomerase inhibitor class is an investigational type of antibacterial inhibitor of DNA gyrase and topoisomerase IV that does not have cross-resistance with the quinolones. Here, we report the evaluation of the in vitro properties of a new series of this type of small molecule. Exemplar compounds selectively and potently inhibited the catalytic activities of Escherichia coli DNA gyrase and topoisomerase IV but did not block the DNA breakage-reunion step. Compounds showed broad-spectrum inhibitory activity against a wide range of Gram-positive and Gram-negative pathogens, including biodefence microorganisms and Mycobacterium tuberculosis No cross-resistance with fluoroquinolone-resistant Staphylococcus aureus and E. coli isolates was observed. Measured MIC 90 values were 4 and 8 μg/ml against a panel of contemporary multidrug-resistant isolates of Acinetobacter baumannii and E. coli , respectively. In addition, representative compounds exhibited greater antibacterial potency than the quinolones against obligate anaerobic species. Spontaneous mutation rates were low, with frequencies of resistance typically <10 -8 against E. coli and A. baumannii at concentrations equivalent to 4-fold the MIC. Compound-resistant E. coli mutants that were isolated following serial passage were characterized by whole-genome sequencing and carried a single Arg38Leu amino acid substitution in the GyrA subunit of DNA gyrase. Preliminary in vitro safety data indicate that the series shows a promising therapeutic index and potential for low human ether-a-go-go-related gene (hERG) inhibition (50% inhibitory concentration [IC 50 ], >100 μM). In summary, the compounds' distinct mechanism of action relative to the fluoroquinolones, whole-cell potency, low potential for resistance development, and favorable in vitro safety profile warrant their continued investigation as potential broad-spectrum antibacterial agents. Copyright © 2017 American Society for Microbiology.

Combined antitumor effects of bee venom and cisplatin on human cervical and laryngeal carcinoma cells and their drug resistant sublines.

PubMed

Gajski, Goran; Čimbora-Zovko, Tamara; Rak, Sanjica; Rožman, Marko; Osmak, Maja; Garaj-Vrhovac, Vera

2014-12-01

In the present study, we investigated the possible combined anticancer ability of bee venom (BV) and cisplatin towards two pairs of tumour cell lines: parental cervical carcinoma HeLa cells and their cisplatin-resistant HeLa CK subline,as well as laryngeal carcinoma HEp-2 cells and their cisplatin-resistant CK2 subline. Additionally, we identified several peptides of BV in the BV sample used in the course of the study and determined the exact concentration of MEL. BV applied alone in concentrations of 30 to 60 μg ml(–1) displayed dose-dependent cytotoxicity against all cell lines tested. Cisplatin-resistant cervical carcinoma cells were more sensitive to BV than their parental cell lines (IC(50) values were 52.50 μg ml(–1) for HeLa vs.47.64 μg ml(–1) for HeLa CK cells), whereas opposite results were obtained for cisplatin-resistant laryngeal carcinoma cells (IC(50) values were 51.98 μg ml(–1) for HEp-2 vs. > 60.00 μg ml(–1) for CK2 cells). Treatment with BV alone induced a necrotic type of cell death, as shown by characteristic morphological features, fast staining with ethidium-bromide and a lack of cleavage of apoptotic marker poly (ADP-ribose) polymerase (PARP) on Western blot. Combined treatment of BV and cisplatin induced an additive and/or weak synergistic effect towards tested cell lines, suggesting that BV could enhance the killing effect of selected cells when combined with cisplatin. Therefore, a greater anticancer effect could be triggered if BV was used in the course of chemotherapy. Our results suggest that combined treatment with BV could be useful from the point of minimizing the cisplatin concentration during chemotherapy, consequently reducing and/or postponing the development of cisplatin resistance.

Hydrogen-deficient Central Stars of Planetary Nebulae

NASA Astrophysics Data System (ADS)

Todt, H.; Kniazev, A. Y.; Gvaramadze, V. V.; Hamann, W.-R.; Pena, M.; Graefener, G.; Buckley, D.; Crause, L.; Crawford, S. M.; Gulbis, A. A. S.; Hettlage, C.; Hooper, E.; Husser, T.-O.; Kotze, P.; Loaring, N.; Nordsieck, K. H.; O'Donoghue, D.; Pickering, T.; Potter, S.; Romero-Colmenero, E.; Vaisanen, P.; Williams, T.; Wolf, M.

2015-06-01

A significant number of the central stars of planetary nebulae (CSPNe) are hydrogen-deficient and are considered as the progenitors of H-deficient white dwarfs. Almost all of these H-deficient CSPNe show a chemical composition of helium, carbon, and oxygen. Most of them exhibit Wolf-Rayet-like emission line spectra and are therefore classified as of spectral type [WC]. In the last years, CSPNe of other Wolf-Rayet spectral subtypes have been identified, namely PB 8 (spectral type [WN/WC]), IC 4663 and Abell 48 (spectral type [WN]). We performed spectral analyses for a number of Wolf-Rayet type central stars of different evolutionary stages with the help of our Potsdam Wolf-Rayet (PoWR) model code for expanding atmospheres to determine relevant stellar parameters. The results of our recent analyses will be presented in the context of stellar evolution and white dwarf formation. Especially the problems of a uniform evolutionary channel for [WC] stars as well as constraints to the formation of [WN] or [WN/WC] subtype stars will be addressed.

The Time-domain Spectroscopic Survey: Target Selection for Repeat Spectroscopy

NASA Astrophysics Data System (ADS)

MacLeod, Chelsea L.; Green, Paul J.; Anderson, Scott F.; Eracleous, Michael; Ruan, John J.; Runnoe, Jessie; Nielsen Brandt, William; Badenes, Carles; Greene, Jenny; Morganson, Eric; Schmidt, Sarah J.; Schwope, Axel; Shen, Yue; Amaro, Rachael; Lebleu, Amy; Filiz Ak, Nurten; Grier, Catherine J.; Hoover, Daniel; McGraw, Sean M.; Dawson, Kyle; Hall, Patrick B.; Hawley, Suzanne L.; Mariappan, Vivek; Myers, Adam D.; Pâris, Isabelle; Schneider, Donald P.; Stassun, Keivan G.; Bershady, Matthew A.; Blanton, Michael R.; Seo, Hee-Jong; Tinker, Jeremy; Fernández-Trincado, J. G.; Chambers, Kenneth; Kaiser, Nick; Kudritzki, R.-P.; Magnier, Eugene; Metcalfe, Nigel; Waters, Chris Z.

2018-01-01

As astronomers increasingly exploit the information available in the time domain, spectroscopic variability in particular opens broad new channels of investigation. Here we describe the selection algorithms for all targets intended for repeat spectroscopy in the Time Domain Spectroscopic Survey (TDSS), part of the extended Baryon Oscillation Spectroscopic Survey within the Sloan Digital Sky Survey (SDSS)-IV. Also discussed are the scientific rationale and technical constraints leading to these target selections. The TDSS includes a large “repeat quasar spectroscopy” (RQS) program delivering ∼13,000 repeat spectra of confirmed SDSS quasars, and several smaller “few-epoch spectroscopy” (FES) programs targeting specific classes of quasars as well as stars. The RQS program aims to provide a large and diverse quasar data set for studying variations in quasar spectra on timescales of years, a comparison sample for the FES quasar programs, and an opportunity for discovering rare, serendipitous events. The FES programs cover a wide variety of phenomena in both quasars and stars. Quasar FES programs target broad absorption line quasars, high signal-to-noise ratio normal broad line quasars, quasars with double-peaked or very asymmetric broad emission line profiles, binary supermassive black hole candidates, and the most photometrically variable quasars. Strongly variable stars are also targeted for repeat spectroscopy, encompassing many types of eclipsing binary systems, and classical pulsators like RR Lyrae. Other stellar FES programs allow spectroscopic variability studies of active ultracool dwarf stars, dwarf carbon stars, and white dwarf/M dwarf spectroscopic binaries. We present example TDSS spectra and describe anticipated sample sizes and results.

The antioxidant activity test by using DPPH method from the white tea using different solvents

NASA Astrophysics Data System (ADS)

Darmajana, Doddy A.; Hadiansyah, Firman; Desnilasari, Dewi

2017-11-01

The solvents used in this study are: aquades, ethanol and glacial acetic acid. The raw material as the source of antioxidants is white tea. Pure Quercetin is used as a comparing antioxidant. The treatment design was the solvent type for extraction, while the antioxidant activity was tested using DPPH method, with IC50 as the reference of antioxidant activity value. The results of antioxidant activity tests with three different solvent types are IC50 of 22,499 µg/mL for aquades, IC50 of 13,317 µg/mL for Ethanol and IC50 of 60,555 µg/mL for Glacial Acetic Acid. As a control of the standard antioxidant activity value of Quercetin is 4,313 µg/mL.

The helium 10830 A line in early-type stars - An atlas of Fabry-Perot scans

NASA Technical Reports Server (NTRS)

Meisel, D. D.; Frank, Z. A.; Packard, M. L.; Saunders, B. A.

1982-01-01

Representative profiles of He I 10830 A in 65 early-type (O6-A1) stars over a wide range of luminosity are presented. The atlas scans were obtained using the Vaughan Fabry-Perot interferometer on the C. E. K. Mees 0.6 m and KPNO 0.9 m telescopes and usually cover a range of plus or minus 15 A at 1 A resolution with sampling distances between 0.5 A and 2 A depending on the photometer integration time required to reach reasonable Poisson counting statistics. The majority of the scans show very shallow, broad features which do not agree with plane-parallel NLTE model atmosphere calculations of the 10830 line by Auer and Mihalas (1972). Difficulties connected with previous theoretical studies of this line are briefly discussed, and suggestions for possible future modifications to the theory are made.

An infrared view of AGN feedback in a type-2 quasar: the case of the Teacup galaxy

NASA Astrophysics Data System (ADS)

Ramos Almeida, C.; Piqueras López, J.; Villar-Martín, M.; Bessiere, P. S.

2017-09-01

We present near-infrared integral field spectroscopy data obtained with Very Large Telescope/Spectrograph for INtegral Field Observations in the Near Infrared (SINFONI) of 'the Teacup galaxy'. The nuclear K-band (1.95-2.45 μm) spectrum of this radio-quiet type-2 quasar reveals a blueshifted broad component of FWHM ˜ 1600-1800 km s-1 in the hydrogen recombination lines (Pa α, Br δ and Br γ) and also in the coronal line [Si VI] λ1.963 μm. Thus, the data confirm the presence of the nuclear ionized outflow previously detected in the optical range and reveal its coronal counterpart. Both the ionized and coronal nuclear outflows are resolved, with seeing-deconvolved full widths at half-maximum of 1.1 ± 0.1 and 0.9 ± 0.1 kpc along position angle (PA) ˜ 72°-74°. This orientation is almost coincident with the radio axis (PA = 77°), suggesting that the radio jet could have triggered the nuclear outflow. In the case of the H2 lines, we do not require a broad component to reproduce the profiles, but the narrow lines are blueshifted by ˜50 km s-1 on average from the galaxy systemic velocity. This could be an indication of the presence of a nuclear molecular outflow, although the bulk of the H2 emission in the inner ˜2 arcsec (˜3 kpc) of the galaxy follows a rotation pattern. We find evidence for kinematically disrupted gas (FWHM > 250 km s-1) at up to 5.6 kpc from the AGN, which can be naturally explained by the action of the outflow. The narrow component of [Si VI] is redshifted with respect to the systemic velocity, unlike any other emission line in the K-band spectrum. This indicates that the region where the coronal lines are produced is not cospatial with the narrow-line region.

NGC 5506 unmasked as a Narrow Line Seyfert 1:. A direct view of the broad line region using near-IR spectroscopy

NASA Astrophysics Data System (ADS)

Nagar, N. M.; Oliva, E.; Marconi, A.; Maiolino, R.

2002-08-01

This letter presents incontrovertible evidence that NGC 5506 is a Narrow Line Seyfert 1 (NLSy1). Our new 0.9-1.4 mu m spectrum of its nucleus clearly shows the permitted O I lambda 1.1287 mu m line (with full width at half maximum <2000 km s-1) and the ``1 micron Fe II lines''. These lines can only originate in the optically-thick broad line region (BLR) and, among Seyfert nuclei the latter series of lines are seen only in NLSy1s. The obscuration to the BLR, derived from a rough estimate of the O I lambda 1.1287 mu m/O I lambda 8446 ratio and from the reddening of the near-IR Paschen lines, is AV > 5. Together, these results make NGC 5506 the first identified case of an optically-obscured NLSy1. This new classification helps explain its radio to X-ray properties, which until now were considered highly anomalous. However, interesting new concerns are raised: e.g., NGC 5506 is unusual in hosting both a ``type 1'' AGN and a nuclear water vapor megamaser. As the brightest known NLSy1, NGC 5506 is highly suitable for study at wavebands less affected by obscuration. Based on observations made with the Italian Telescopio Nazionale Galileo (TNG) operated on the island of La Palma by the Centro Galileo Galilei of the INAF (Istituto Nazionale di Astrofisica) at the Spanish Observatorio del Roque de los Muchachos of the Instituto de Astrofisica de Canarias.

Effects of lactoferrin on the production of interferon-λ by the human intestinal epithelial cell line HT-29.

PubMed

Shin, Kouichirou; Oda, Hirotsugu; Wakabayashi, Hiroyuki; Yamauchi, Koji; Abe, Fumiaki

2017-02-01

We examined the in-vitro effects of bovine lactoferrin (LF) on the production of interferon-λ (IFN-λ), an antiviral cytokine important for the defense of enterocytes, using the human intestinal epithelial cell line HT-29. HT-29 cell cultures were treated with LF for 1 h, and the cultures were stimulated with polyinosinic-polycytidylic acid (poly I:C). LF increased the concentration of IFN-λ in the culture supernatant after stimulation in a dose-dependent manner. A similar increase in the concentration of IFN-λ was observed in the supernatant of cells washed between treatment with LF and stimulation with poly I:C. At 6 and 24 h after stimulation with poly I:C (early and late phases, respectively) treated cultures contained significantly higher concentrations of IFN-λ1 in the culture supernatant, and significantly higher IFN-λ1 and IFN-λ2 mRNA levels, than controls. These results suggest that LF activates the innate cellular immunity of the enterocytes to double-stranded RNA and increases the production of IFN-λ.

MASTER OT J014638.27+041324.4 is a Young Type IIP Supernova

NASA Astrophysics Data System (ADS)

Zheng, W.; Kelly, P. L.; Clubb, K. I.; Filippenko, A. V.

2013-12-01

We report that a CCD spectrum (range 350-1000 nm) of MASTER OT J014638.27+041324.4 (Shurpakov et al., ATel #5630) was obtained on Dec 6.5 UT with the Shane 3-m reflector (+Kast spectrograph) at Lick Observatory. The spectrum shows a blue continuum and weak, broad hydrogen Balmer lines having P-Cyg profiles, indicating that the object is a young Type IIP supernova. Weak He I 587.6 nm is also present.

Comparative Efficacy of Intracoronary Allogeneic Mesenchymal Stem Cells and Cardiosphere-Derived Cells in Swine with Hibernating Myocardium

PubMed Central

Weil, Brian R.; Suzuki, Gen; Leiker, Merced M.; Fallavollita, James A.; Canty, John M.

2015-01-01

Rationale Allogeneic bone marrow-derived mesenchymal stem cells (MSCs) and cardiosphere-derived cells (CDCs) have each entered clinical trials but a direct comparison of these cell types has not been performed in a large animal model of hibernating myocardium. Objective Using completely blinded methodology, compare the efficacy of global intracoronary allogeneic MSCs (icMSCs, ~35×106) and CDCs (icCDCs, ~35×106) vs. vehicle in cyclosporine-immunosuppressed swine with a chronic LAD stenosis (n=26). Methods and Results Studies began 3-months after instrumentation when wall-thickening (%WT) was reduced (LAD%WT 38±11% (mean ± SD) vs. 83±26% in remote, p<0.01) and similar among groups. Four-weeks after treatment, LAD%WT increased similarly following icCDCs and icMSCs, while it remained depressed in vehicle-treated controls (icMSCs: 51±13%; icCDCs: 51±17%; vehicle: 34±3%, treatments p<0.05 vs. vehicle). There was no change in myocardial perfusion. Both icMSCs and icCDCs increased LAD myocyte nuclear density (icMSCs: 1601±279 nuclei/mm2, icCDCs: 1569±294 nuclei/mm2, vehicle: 973±181 nuclei/mm2, treatments p<0.05 vs. vehicle) and reduced myocyte diameter (icMSCs: 16.4±1.5 μm, icCDCs: 16.8±1.2 μm, vehicle: 20.2±3.7 μm, treatments p<0.05 vs. vehicle) to the same extent. Similar changes in myocyte nuclear density and diameter were observed in the remote region of cell-treated animals. Cell fate analysis using Y-FISH demonstrated rare cells from sex-mismatched donors. Conclusions Allogeneic icMSCs and icCDCs exhibit comparable therapeutic efficacy in a large animal model of hibernating myocardium. Both cell types produced equivalent increases in regional function and stimulated myocyte regeneration in ischemic and remote myocardium. The activation of endogenous myocyte proliferation and regression of myocyte cellular hypertrophy support a common mechanism of cardiac repair. PMID:26271689

Traditional medicines used by Q'eqchi' Maya to treat diabetic symptoms and their antiglycation potential.

PubMed

Ferrier, J; Saleem, A; Carter Ramirez, A; Liu, R; Chen, Eric; Pesek, T; Cal, V; Balick, M; Arnason, J T

2018-06-21

Because of the recent increase in type 2 diabetes and the need for complementary treatments in remote communities in many parts of the world, we undertook a study of treatments for diabetic symptoms used by traditional Q'eqchi' Maya healers of Belize. We used quantitative ethnobotany to rank culturally important taxa and subsequent pharmacological and phytochemical studies to assess bioactivity. Antidiabetic plants identified in field interviews with traditional healers were ranked by syndromic importance value (SIV) based on 15 symptoms of diabetes.. Species ranked with high SIV were tested in an assay relevant to many diabetes complications, the advanced glycation endproduct (AGE) inhibition assay. Active principles were identified by phytochemical analysis and bioassay. We collected over 70 plant species having a promising SIV score. The plants represented a broad range of neotropical taxa. Selected Q'eqchi' antidiabetic plants with high SIV were collected in bulk and tested in the advanced glycation endproduct (AGE) inhibition assay. All plant extracts showed AGE inhibition and the half maximal inhibitory concentration (IC 50 ) ranged from 40.8 to 733µg/mL, while the most active species was Tynanthus guatemalensis Donn (Bignoniaceae). A linear regression showed a significant relationship between 1/ IC 50 and SIV. Phytochemical analysis revealed the presence of verbascoside, as a major component and active principle of the T guatemalensis which had an IC 50 = 5.1µg/mL, comparable to the positive control quercetin. The results reveal a rich botanical tradition of antidiabetic symptom treatments among the Q'eqchi'. Study of highly ranked plants revealed their activity in AGE inhibition correlated with SIV. T. guatemalensis was identified as a promising species for further evaluation and local use. Copyright © 2018. Published by Elsevier B.V.

Lithium Abundances in the Young Open Cluster IC 2602

NASA Technical Reports Server (NTRS)

Randich, S.; Aharpour, N.; Pallavicini, R.; Prosser, C. F.; Stauffer, J. R.

1997-01-01

We have obtained high-resolution spectra for 28 candidate late-type stars in the 30 Myr old cluster IC 2602. NLTE Li abundances have been derived from measured equivalent widths. The log n(Li) - T(sub eff) and log n(Li) - mass distributions for our sample stars have been compared with those of the Pleiades and alpha Persei. Our data show that F stars in the three clusters have the same lithium content, which corresponds to the initial content for Pop. I stars. G and early-K IC 2602 stars are, on average, somewhat more Li-rich than their counterparts in the two slightly older clusters. Finally, the latest-type IC 2602 stars are heavily Li depleted, with their Li content being as low as the lowest measured among the Pleiades. As in the Pleiades and alpha Per, a star-to-star scatter in lithium is observed among 30 Myr old late-K/early-K dwarfs in IC 2602, indicating that this spread develops in the pre-main sequence phases.

Iterative categorization (IC): a systematic technique for analysing qualitative data

PubMed Central

2016-01-01

Abstract The processes of analysing qualitative data, particularly the stage between coding and publication, are often vague and/or poorly explained within addiction science and research more broadly. A simple but rigorous and transparent technique for analysing qualitative textual data, developed within the field of addiction, is described. The technique, iterative categorization (IC), is suitable for use with inductive and deductive codes and can support a range of common analytical approaches, e.g. thematic analysis, Framework, constant comparison, analytical induction, content analysis, conversational analysis, discourse analysis, interpretative phenomenological analysis and narrative analysis. Once the data have been coded, the only software required is a standard word processing package. Worked examples are provided. PMID:26806155

Application of Receiver Operating Characteristic Analysis to Refine the Prediction of Potential Digoxin Drug Interactions

PubMed Central

Ellens, Harma; Deng, Shibing; Coleman, JoAnn; Bentz, Joe; Taub, Mitchell E.; Ragueneau-Majlessi, Isabelle; Chung, Sophie P.; Herédi-Szabó, Krisztina; Neuhoff, Sibylle; Palm, Johan; Balimane, Praveen; Zhang, Lei; Jamei, Masoud; Hanna, Imad; O’Connor, Michael; Bednarczyk, Dallas; Forsgard, Malin; Chu, Xiaoyan; Funk, Christoph; Guo, Ailan; Hillgren, Kathleen M.; Li, LiBin; Pak, Anne Y.; Perloff, Elke S.; Rajaraman, Ganesh; Salphati, Laurent; Taur, Jan-Shiang; Weitz, Dietmar; Wortelboer, Heleen M.; Xia, Cindy Q.; Xiao, Guangqing; Yamagata, Tetsuo

2013-01-01

In the 2012 Food and Drug Administration (FDA) draft guidance on drug-drug interactions (DDIs), a new molecular entity that inhibits P-glycoprotein (P-gp) may need a clinical DDI study with a P-gp substrate such as digoxin when the maximum concentration of inhibitor at steady state divided by IC50 ([I1]/IC50) is ≥0.1 or concentration of inhibitor based on highest approved dose dissolved in 250 ml divide by IC50 ([I2]/IC50) is ≥10. In this article, refined criteria are presented, determined by receiver operating characteristic analysis, using IC50 values generated by 23 laboratories. P-gp probe substrates were digoxin for polarized cell-lines and N-methyl quinidine or vinblastine for P-gp overexpressed vesicles. Inhibition of probe substrate transport was evaluated using 15 known P-gp inhibitors. Importantly, the criteria derived in this article take into account variability in IC50 values. Moreover, they are statistically derived based on the highest degree of accuracy in predicting true positive and true negative digoxin DDI results. The refined criteria of [I1]/IC50 ≥ 0.03 and [I2]/IC50 ≥ 45 and FDA criteria were applied to a test set of 101 in vitro-in vivo digoxin DDI pairs collated from the literature. The number of false negatives (none predicted but DDI observed) were similar, 10 and 12%, whereas the number of false positives (DDI predicted but not observed) substantially decreased from 51 to 40%, relative to the FDA criteria. On the basis of estimated overall variability in IC50 values, a theoretical 95% confidence interval calculation was developed for single laboratory IC50 values, translating into a range of [I1]/IC50 and [I2]/IC50 values. The extent by which this range falls above the criteria is a measure of risk associated with the decision, attributable to variability in IC50 values. PMID:23620486

Genome expression analysis in yeast reveals novel transcriptional regulation by inositol and choline and new regulatory functions for Opi1p, Ino2p, and Ino4p.

PubMed

Santiago, Teresa C; Mamoun, Choukri Ben

2003-10-03

In Saccharomyces cerevisiae, genes encoding phospholipid-synthesizing enzymes are regulated by inositol and choline (IC). The current model suggests that when these precursors become limiting, the transcriptional complex Ino2p-Ino4p activates the expression of these genes, whereas repression requires Opi1p and occurs when IC are available. In this study, microarray-based expression analysis was performed to assess the global transcriptional response to IC in a wild-type strain and in the opi1delta, ino2delta, and ino4delta null mutant strains. Fifty genes were either activated or repressed by IC in the wild-type strain, including three already known IC-repressed genes. We demonstrated that the IC response was not limited to genes involved in membrane biogenesis, but encompassed various metabolic pathways such as biotin synthesis, one-carbon compound metabolism, nitrogen-containing compound transport and degradation, cell wall organization and biogenesis, and acetyl-CoA metabolism. The expression of a large number of IC-regulated genes did not change in the opi1delta, ino2delta, and ino4delta strains, thus implicating new regulatory elements in the IC response. Our studies revealed that Opi1p, Ino2p, and Ino4p have dual regulatory activities, acting in both positive and negative transcriptional regulation of a large number of genes, most of which are not regulated by IC and only a subset of which is involved in membrane biogenesis. These data provide the first global response profile of yeast to IC and reveal novel regulatory mechanisms by these precursors.

Migration of Older to New Digital Control Systems in Nuclear Power Plant Main Control Rooms

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

Kovesdi, Casey Robert; Joe, Jeffrey Clark

The United States (U.S.) Department of Energy (DOE) Office of Nuclear Energy (NE) has the primary mission to advance nuclear power by resolving socio-technical issues through research and development (R&D). One DOE-NE activity supporting this mission is the Light Water Reactor Sustainability (LWRS) program. LWRS has the overall objective to sustain the operation of existing commercial nuclear power plants (NPPs) through conducting R&D across multiple “pathways,” or R&D focus areas. The Advanced Instrumentation, Information, and Control (II&C) Systems Technologies pathway conducts targeted R&D to address aging and reliability concerns with the legacy instrumentation and control (I&C) and related information systemsmore » in operating U.S. NPPs. This work involves (1) ensuring that legacy analog II&C systems are not life-limiting issues for the LWR fleet, and (2) implementing digital II&C technology in a manner that enables broad innovation and business improvement in the NPP operating model. Under the LWRS Advanced II&C pathway, Human Factors experts at Idaho National Laboratory (INL) have been conducting R&D in support of NPP main control room (MCR) modernization activities. Work in prior years has focused on migrating analog I&C systems to new digital I&C systems (). In fiscal year 2016 (FY16), one new focus area for this research is migrating older digital I&C systems to new and advanced digital I&C systems. This report summarizes a plan for conducting a digital-to-digital migration of a legacy digital I&C system to a new digital I&C system in support of control room modernization activities.« less

Use of optical technique for inspection of warpage of IC packages

NASA Astrophysics Data System (ADS)

Toh, Siew-Lok; Chau, Fook S.; Ong, Sim Heng

2001-06-01

The packaging of IC packages has changed over the years, form dual-in-line, wire-bond, and pin-through-hole in printed wiring board technologies in the 1970s to ball grid array, chip scale and surface mount technologies in the 1990s. Reliability has been a big problem for manufacturers for some moisture-sensitive packages. One of the potential problems in plastic IC packages is moisture-induced popcorn effect which can arise during the reflow process. Shearography is a non-destructive inspection technique that may be used to detect the delamination and warpage of IC packages. It is non-contacting and permits a full-field observation of surface displacement derivatives. Another advantage of this technique is that it is able to give the real-time formation of the fringes which indicate flaws in the IC package under real-time simulation condition of Surface Mount Technology (SMT) IR reflow profile. It is extremely fast and convenient to study the true behavior of the packaging deformation during the SMT process. It can be concluded that shearography has the potential for the real- time detection, in situ and non-destructive inspection of IC packages during the surface mount process.

A C3(H20) recycling pathway is a component of the intracellular complement system

PubMed Central

Elvington, Michelle; Bertram, Paula; Atkinson, John P.

2017-01-01

An intracellular complement system (ICS) has recently been described in immune and nonimmune human cells. This system can be activated in a convertase-independent manner from intracellular stores of the complement component C3. The source of these stores has not been rigorously investigated. In the present study, Western blotting identified a band corresponding to C3 in freshly isolated human peripheral blood cells that was absent in corresponding cell lines. One difference between native cells and cell lines was the time absent from a fluid-phase complement source; therefore, we hypothesized that loading C3 from plasma was a route of establishing intracellular C3 stores. We found that many types of human cells specifically internalized C3(H2O), the hydrolytic product of C3, and not native C3, from the extracellular milieu. Uptake was rapid, saturable, and sensitive to competition with unlabeled C3(H2O), indicating a specific mechanism of loading. Under steady-state conditions, approximately 80% of incorporated C3(H2O) was returned to the extracellular space. These studies identify an ICS recycling pathway for C3(H2O). The loaded C3(H2O) represents a source of C3a, and its uptake altered the cytokine profile of activated CD4+ T cells. Importantly, these results indicate that the impact of soluble plasma factors should be considered when performing in vitro studies assessing cellular immune function. PMID:28192370

In vitro growth inhibition and cytotoxicity of Euphorbia caducifolia against four human cancer cell lines and its phytochemical characterisation.

PubMed

Bano, Shaista; Siddiqui, Bina Shaheen; Farooq, Ahsana Dar; Begum, Sabira; Siddiqui, Faheema; Kashif, Muhammad; Azhar, Mudassar

2017-12-01

Several Euphorbia species have been used in folklore as cancer remedies, however, scientific studies on the cytotoxicity (in vitro studies) of Euphorbia caducifolia are lacking. In present study, anticancer potential of E. caducifolia aerial parts ethanol extract and its fractions were evaluated against human lung (NCI-H460), breast (MCF-7), prostate (PC-3) and cervical (HeLa) cancer cell lines, using sulphorhodamine-B in vitro cytotoxicity (in vitro studies) assay. The ethanol extract demonstrated growth inhibitory effect against all aforementioned cancer cell lines with IC 50 , 19-135 μg/mL and LC 50 , ~220 μg/mL, and its petroleum ether fraction obtained on bioactivity guided fraction showed highest activity with IC 50 , 28-70 μg/mL and LC 50 , 71 μg/mL against NCI-H460 and MCF-7 cell lines. Its phytochemicals were analysed by gas chromatography-mass spectrometry (GC-MS). The present study provides scientific justification for its traditional use against cancer.

New 15-membered tetraaza (N4) macrocyclic ligand and its transition metal complexes: Spectral, magnetic, thermal and anticancer activity

NASA Astrophysics Data System (ADS)

El-Boraey, Hanaa A.; EL-Gammal, Ohyla A.

2015-03-01

Novel tetraamidemacrocyclic 15-membered ligand [L] i.e. naphthyl-dibenzo[1,5,9,12]tetraazacyclopentadecine-6,10,11,15-tetraoneand its transition metal complexes with Fe(II), Co(II), Ni(II), Cu(II), Ru(III) and Pd(II) have been synthesized and characterized by elemental analysis, spectral, thermal as well as magnetic and molar conductivity measurements. On the basis of analytical, spectral (IR, MS, UV-Vis, 1H NMR and EPR) and thermal studies distorted octahedral or square planar geometry has been proposed for the complexes. The antitumor activity of the synthesized ligand and some complexes against human breast cancer cell lines (MCF-7) and human hepatocarcinoma cell lines (HepG2) has been studied. The complexes (IC50 = 2.27-2.7, 8.33-31.1 μg/mL, respectively) showed potent antitumor activity, towards the former cell lines comparable with their ligand (IC50 = 13, 26 μg/mL, respectively). The results show that the activity of the ligand towards breast cancer cell line becomes more pronounced and significant when coordinated to the metal ion.