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  • 1
    Online Resource
    Online Resource
    TTR variants in patients with dilated cardiomyopathy: An investigation of the DCM Precision Medicine Study
    Elsevier BV ; 2022
    In:  Genetics in Medicine Vol. 24, No. 7 ( 2022-07), p. 1495-1502
    Details
    In: Genetics in Medicine, Elsevier BV, Vol. 24, No. 7 ( 2022-07), p. 1495-1502
    Type of Medium: Online Resource
    ISSN: 1098-3600
    URL: Article
    DOI: 10.1016/j.gim.2022.03.011
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2022
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  • 2
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    Comprehensive Molecular Characterization of Pheochromocytoma and Paraganglioma
    Elsevier BV ; 2017
    In:  Cancer Cell Vol. 31, No. 2 ( 2017-02), p. 181-193
    Details
    In: Cancer Cell, Elsevier BV, Vol. 31, No. 2 ( 2017-02), p. 181-193
    Type of Medium: Online Resource
    ISSN: 1535-6108
    URL: Article
    DOI: 10.1016/j.ccell.2017.01.001
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2017
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    SSG: 12
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  • 3
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    Evaluation of Radiative Transfer Models With Clouds
    American Geophysical Union (AGU) ; 2018
    In:  Journal of Geophysical Research: Atmospheres Vol. 123, No. 11 ( 2018-06-16), p. 6142-6157
    Details
    In: Journal of Geophysical Research: Atmospheres, American Geophysical Union (AGU), Vol. 123, No. 11 ( 2018-06-16), p. 6142-6157
    Abstract: In the 900‐cm −1 atmospheric window channel several Radiative Transfer Models have a better than 0.95 correlation between the histogram derived from the observations and those derived from the calculations Differences in the bias between observations and calculations for the 2,616‐cm −1 atmospheric window channel are not inconsistent with results at 900 cm −1 if the daytime calculations use full scattering Differences in the cloud physics and cloud overlap assumptions between Radiative Transfer Models result in a standard deviation of the pairwise difference of between 6 and 12 K; differences due to the cloud overlap assumption alone result in a 3‐K standard deviation
    Type of Medium: Online Resource
    ISSN: 2169-897X , 2169-8996
    URL: Article
    DOI: 10.1029/2017JD028063
    Language: English
    Publisher: American Geophysical Union (AGU)
    Publication Date: 2018
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  • 4
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    Error-weighted maximum likelihood (EWML): a new statistically based method to cluster quantitative micropaleontological data
    Cambridge University Press (CUP) ; 1993
    In:  Journal of Paleontology Vol. 67, No. 3 ( 1993-05), p. 475-486
    Details
    In: Journal of Paleontology, Cambridge University Press (CUP), Vol. 67, No. 3 ( 1993-05), p. 475-486
    Abstract: The advent of readily available computer-based clustering packages has created some controversy in the micropaleontological community concerning the use and interpretation of computer-based biofacies discrimination. This is because dramatically different results can be obtained depending on methodology. The analysis of various clustering techniques reveals that, in most instances, no statistical hypothesis is contained in the clustering model and no basis exists for accepting one biofacies partitioning over another. Furthermore, most techniques do not consider standard error in species abundances and generate results that are not statistically relevant. When many rare species are present, statistically insignificant differences in rare species can accumulate and overshadow the significant differences in the major species, leading to biofacies containing members having little in common. A statistically based “error-weighted maximum likelihood” (EWML) clustering method is described that determines biofacies by assuming that samples from a common biofacies are normally distributed. Species variability is weighted to be inversely proportional to measurement uncertainty. The method has been applied to samples collected from the Fraser River Delta marsh and shows that five distinct biofacies can be resolved in the data. Similar results were obtained from readily available packages when the data set was preprocessed to reduce the number of degrees of freedom. Based on the sample results from the new algorithm, and on tests using a representative micropaleontological data set, a more conventional iterative processing method is recommended. This method, although not statistical in nature, produces similar results to EWML (not commercially available yet) with readily available analysis packages. Finally, some of the more common clustering techniques are discussed and strategies for their proper utilization are recommended.
    Type of Medium: Online Resource
    ISSN: 0022-3360 , 1937-2337
    URL: Article
    DOI: 10.1017/S0022336000036921
    Language: English
    Publisher: Cambridge University Press (CUP)
    Publication Date: 1993
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  • 5
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    Heightening Energetic Stress Selectively Targets LKB1-Deficient Non–Small Cell Lung Cancers
    American Association for Cancer Research (AACR) ; 2015
    In:  Cancer Research Vol. 75, No. 22 ( 2015-11-15), p. 4910-4922
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 75, No. 22 ( 2015-11-15), p. 4910-4922
    Abstract: Inactivation of the LKB1 tumor suppressor is a frequent event in non–small cell lung carcinoma (NSCLC) leading to the activation of mTOR complex 1 (mTORC1) and sensitivity to the metabolic stress inducer phenformin. In this study, we explored the combinatorial use of phenformin with the mTOR catalytic kinase inhibitor MLN0128 as a treatment strategy for NSCLC bearing comutations in the LKB1 and KRAS genes. NSCLC is a genetically and pathologically heterogeneous disease, giving rise to lung tumors of varying histologies that include adenocarcinomas and squamous cell carcinomas (SCC). We demonstrate that phenformin in combination with MLN0128 induced a significant therapeutic response in KRAS/LKB1–mutant human cell lines and genetically engineered mouse models of NSCLC that develop both adenocarcinomas and SCCs. Specifically, we found that KRAS/LKB1–mutant lung adenocarcinomas responded strongly to phenformin + MLN0128 treatment, but the response of SCCs to single or combined treatment with MLN0128 was more attenuated due to acquired resistance to mTOR inhibition through modulation of the AKT-GSK signaling axis. Combinatorial use of the mTOR inhibitor and AKT inhibitor MK2206 robustly inhibited the growth and viability of squamous lung tumors, thus providing an effective strategy to overcome resistance. Taken together, our findings define new personalized therapeutic strategies that may be rapidly translated into clinical use for the treatment of KRAS/LKB1–mutant adenocarcinomas and squamous cell tumors. Cancer Res; 75(22); 4910–22. ©2015 AACR.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/0008-5472.CAN-15-0797
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2015
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  • 6
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    Abstract 2449: Identifying therapy responsive and resistant LKB1 mutant non-small cell lung tumor populations
    American Association for Cancer Research (AACR) ; 2014
    In:  Cancer Research Vol. 74, No. 19_Supplement ( 2014-10-01), p. 2449-2449
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 74, No. 19_Supplement ( 2014-10-01), p. 2449-2449
    Abstract: The LKB1/STK11 tumor suppressor is mutationally inactivated in ∼30% of sporadic non-small cell lung cancers (NSCLC), and to date there are no agents targeting loss of LKB1 in lung cancer. LKB1 is the major upstream kinase activating the energy sensing kinase AMPK under conditions of low intracellular ATP. In cells defective for LKB1, metabolic stress is not appropriately sensed and energy homeostasis is not efficiently restored, providing an Achilles heel to target in tumors with this genetic lesion. Importantly, LKB1-deficient (LKB1-/-) NSCLC cells are unable to restore energy homeostasis in response to biguanide-induced energy stress and preferentially undergo apoptosis. As targeted therapy for LKB1 mutant tumors are needed, we explored the use of the metabolic stress agent phenformin as an anti- cancer drug to target the LKB1-/- NSCLC. Phenformin is a biguanide that has historically used to treat metabolic disease and we demonstrated that it potently induced apoptosis in LKB1-/- lung tumors and significantly prolonged survival in genetically engineered mouse models (GEMMs) of lung cancer in mice bearing tumors with mutated Kras and Lkb1 genes but not mice with compound mutations in Kras and p53. Our pre-clinical studies suggest phenformin may be used as a cancer metabolism-based prevention agent or therapeutic to selectively target LKB1-/- pulmonary epithelial cells and tumors. However, phenformin as a single agent therapy was not curative, highlighting the need to find additional therapies to prevent or target LKB1-/- lung tumors in combination with phenformin. We have previously shown LKB1 loss leads to mTORC1 hyperactivation therefore we explored the combinatorial use of phenformin with the mTOR kinase inhibitor MLN128. We tested phenformin and MLN128 together on our human and mouse models of lung cancer and demonstrated the two drugs cooperated together to enhance apoptosis and reduce proliferation. KrasG12D driven, Lkb1-/- mice develop both adenocarcinoma (ADC) and squamous cell carcinomas (SQCC). We performed 18FDG-PET and CT guided pre-clinical studies assessing phenformin + MLN128 as a combinatorial therapy in vivo using our Lkb1-/- GEMMs of NSCLC. We discovered that lung ADC were highly responsive to the combination therapy while the SQCC lung tumor populations appear highly resistant. These findings carry important clincal relevance as currently there are limited options for patients with LKB1-mutant tumors. Here we define the hypersensitivity of LKB1-/- lung ADC tumors to metabolic stress and mTOR inhibition while in parallel identifying a therapy resistant SQCC lung tumor population. These results suggest phenformin in combination with mTOR kinase inhibitors may find clinical utility to treat LKB1 mutant lung ADC. Citation Format: Evan Abt, Milica Momcilovic, Atsuko Seki, Robert McMickle, David Stout, Michael C. Fishbein, David B. Shackelford. Identifying therapy responsive and resistant LKB1 mutant non-small cell lung tumor populations. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2449. doi:10.1158/1538-7445.AM2014-2449
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2014-2449
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2014
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  • 7
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    Aerosol source plume physical characteristics from space-based multiangle imaging
    American Geophysical Union (AGU) ; 2007
    In:  Journal of Geophysical Research Vol. 112, No. D11 ( 2007-06-07)
    Details
    In: Journal of Geophysical Research, American Geophysical Union (AGU), Vol. 112, No. D11 ( 2007-06-07)
    Type of Medium: Online Resource
    ISSN: 0148-0227
    URL: Article
    DOI: 10.1029/2006JD007647
    Language: English
    Publisher: American Geophysical Union (AGU)
    Publication Date: 2007
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    SSG: 16,13
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  • 8
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    Validation studies using multiwavelength Cryogenic Limb Array Etalon Spectrometer (CLAES) observations of stratospheric aerosol
    American Geophysical Union (AGU) ; 1996
    In:  Journal of Geophysical Research: Atmospheres Vol. 101, No. D6 ( 1996-04-30), p. 9757-9773
    Details
    In: Journal of Geophysical Research: Atmospheres, American Geophysical Union (AGU), Vol. 101, No. D6 ( 1996-04-30), p. 9757-9773
    Abstract: Validation studies of multiwavelength Cryogenic Limb Array Etalon Spectrometer (CLAES) observations of stratospheric aerosol are discussed. An error analysis of the CLAES aerosol extinction data is presented. Aerosol extinction precision values are estimated at latitudes and times at which consecutive Upper Atmosphere Research Satellite (UARS) orbits overlap. Comparisons of CLAES aerosol data with theoretical Mie calculations, based upon in situ particle size measurements at Laramie, Wyoming, are presented. CLAES aerosol data are also compared to scaled aerosol extinction measured by the Stratospheric Aerosol and Gas Experiment (SAGE II) and Atmospheric Trace Molecule Spectroscopy (ATMOS) experiments. Observed and calculated extinction spectra, from CLAES, Improved Stratospheric and Mesospheric Sounder (ISAMS), and Halogen Occultation Experiment (HALOE) data, are compared. CLAES extinction data have precisions between 10 and 25%, instrumental biases near 30%, and accuracies between 33 and 43%.
    Type of Medium: Online Resource
    ISSN: 0148-0227
    URL: Article
    DOI: 10.1029/95JD03225
    Language: English
    Publisher: American Geophysical Union (AGU)
    Publication Date: 1996
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    detail.hit.zdb_id: 2016810-X
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    detail.hit.zdb_id: 3094268-8
    detail.hit.zdb_id: 710256-2
    detail.hit.zdb_id: 2016804-4
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    SSG: 16,13
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  • 9
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    Equatorial Kelvin wave variability during 1992 and 1993
    American Geophysical Union (AGU) ; 1995
    In:  Journal of Geophysical Research: Atmospheres Vol. 100, No. D3 ( 1995-03-20), p. 5193-5202
    Details
    In: Journal of Geophysical Research: Atmospheres, American Geophysical Union (AGU), Vol. 100, No. D3 ( 1995-03-20), p. 5193-5202
    Abstract: Temperature and ozone data from the Microwave Limb Sounder (MLS) instrument on UARS are used to analyze the variability of Kelvin wave activity during the first two years of the UARS mission. The analysis is carried out using the asynoptic mapping technique. Time frequency plots for zonal wavenumbers 1 and 2, at two heights representing the middle stratosphere and the stratopause, respectively, are used to analyze the temporal variability of the waves, and its possible relationship to the equatorial quasi‐biennial oscillation (QBO) and semiannual oscillation (SAO). Kelvin wave activity reaches a maximum during the solstice seasons and almost disappears during the equinoxes, in agreement with previous studies. Eastward propagating variance is estimated for wave periods from 4 to 20 days, at all UARS pressure surfaces currently available for MLS. The semiannual modulation of variance is observed to extend down to the lower limits of the height ranges of the temperature and ozone retrievals. Furthermore, a superposed QBO modulation is detected up to the stratopause. Comparison between the variance in eastward propagating waves and the mean zonal wind shows a possible participation of kelvin waves in the forcing of the QBO. At the stratopause the role of Kelvin waves in forcing the SAO appears to be limited, in agreement with previous results. Between the 21‐hPa and 4.6‐hPa surfaces there appears to be a transition zone where there is no clear relationship between Kelvin wave activity and mean zonal flow acceleration.
    Type of Medium: Online Resource
    ISSN: 0148-0227
    URL: Article
    DOI: 10.1029/94JD02330
    Language: English
    Publisher: American Geophysical Union (AGU)
    Publication Date: 1995
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    detail.hit.zdb_id: 2220777-6
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    SSG: 16,13
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  • 10
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    The radiative consistency of Atmospheric Infrared Sounder and Moderate Resolution Imaging Spectroradiometer cloud retrievals
    American Geophysical Union (AGU) ; 2007
    In:  Journal of Geophysical Research Vol. 112, No. D9 ( 2007-05-01)
    Details
    In: Journal of Geophysical Research, American Geophysical Union (AGU), Vol. 112, No. D9 ( 2007-05-01)
    Type of Medium: Online Resource
    ISSN: 0148-0227
    URL: Article
    DOI: 10.1029/2006JD007486
    Language: English
    Publisher: American Geophysical Union (AGU)
    Publication Date: 2007
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    detail.hit.zdb_id: 3094181-7
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    detail.hit.zdb_id: 2220777-6
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    SSG: 16,13
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