Evaluation of Geostationary Lightning Mapper (GLM) Navigation Performance with the INR Performance Assessment Toolset (IPATS)

The GOES-R flight project has developed the Image Navigation and Registration (INR) Performance Assessment Tool Set (IPATS) to perform independent INR evaluations of the optical instruments on the GOES-R series spacecraft. In this presentation, we document the development of navigation (NAV) evaluation capabilities within IPATS for the Geostationary Lightning Mapper (GLM). We also discuss the post-processing quality filtering developed for GLM NAV, and present example results for several GLM background image datasets. Initial results suggest that GOES-16 GLM is compliant with navigation requirements

New age constraints for the Salamanca Formation and lower Río Chico Group in the western San Jorge Basin, Patagonia, Argentina: Implications for Cretaceous-Paleogene extinction recovery and land mammal age correlations

The Salamanca Formation of the San Jorge Basin (Patagonia, Argentina) preserves critical records of Southern Hemisphere Paleocene biotas, but its age remains poorly resolved, with estimates ranging from Late Cretaceous to middle Paleocene. We report a multi-disciplinary geochronologic study of the Salamanca Formation and overlying Rio Chico Group in the western part of the basin. New constraints include (1) an 40Ar/39Ar age determination of 67.31 ± 0.55 Ma from a basalt flow underlying the Salamanca Formation, (2) micropaleontological results indicating an early Danian age for the base of the Salamanca Formation, (3) laser ablation HR-MC-ICP-MS (high resolution-multi collector-inductively coupled plasma-mass spectrometry) U-Pb ages and a high-resolution TIMS (thermal ionization mass spectrometry) age of 61.984 ± 0.041(0.074)[0.100] Ma for zircons from volcanic ash beds in the Penas Coloradas Formation (Rio Chico Group), and (4) paleomagnetic results indicating that the Salamanca Formation in this area is entirely of normal polarity, with reversals occurring in the Rio Chico Group. Placing these new age constraints in the context of a sequence stratigraphic model for the basin, we correlate the Salamanca Formation in the study area to Chrons C29n and C28n, with the Banco Negro Inferior (BNI), a mature widespread fossiliferous paleosol unit at the top of the Salamanca Formation, corresponding to the top of Chron C28n. The diverse paleobotanical assemblages from this area are here assigned to C28n (64.67–63.49 Ma), ∼2–3 million years older than previously thought, adding to growing evidence for rapid Southern Hemisphere floral recovery after the Cretaceous-Paleogene extinction. Important Peligran and “Carodnia” zone vertebrate fossil assemblages from coastal BNI and Penas Coloradas exposures are likely older than previously thought and correlate to the early Torrejonian and early Tiffanian North American Land Mammal Ages, respectively.Centro de Investigaciones Geográfica

New age constraints for the Salamanca Formation and lower Río Chico Group in the western San Jorge Basin, Patagonia, Argentina: Implications for cretaceous-paleogene extinction recovery and land mammal age correlations

The Salamanca Formation of the San Jorge Basin (Patagonia, Argentina) preserves critical records of Southern Hemisphere Paleocene biotas, but its age remains poorly resolved, with estimates ranging from Late Cretaceous to middle Paleocene. We report a multi-disciplinary geochronologic study of the Salamanca Formation and overlying Río Chico Group in the western part of the basin. New constraints include (1) an 40Ar/39Ar age determination of 67.31 ± 0.55 Ma from a basalt flow underlying the Salamanca Formation, (2) micropaleontological results indicating an early Danian age for the base of the Salamanca Formation, (3) laser ablation HR-MC-ICP-MS (high resolutionmulti collector-inductively coupled plasmamass spectrometry) U-Pb ages and a highresolution TIMS (thermal ionization mass spectrometry) age of 61.984 ± 0.041(0.074) [0.100] Ma for zircons from volcanic ash beds in the Peñas Coloradas Formation (Río Chico Group), and (4) paleomagnetic results indicating that the Salamanca Formation in this area is entirely of normal polarity, with reversals occurring in the Río Chico Group. Placing these new age constraints in the context of a sequence stratigraphic model for the basin, we correlate the Salamanca Formation in the study area to Chrons C29n and C28n, with the Banco Negro Inferior (BNI), a mature widespread fossiliferous paleosol unit at the top of the Salamanca Formation, corresponding to the top of Chron C28n. The diverse paleo botanical assemblages from this area are here assigned to C28n (64.67- 63.49 Ma), ̃2-3 million years older than previously thought, adding to growing evidence for rapid Southern Hemisphere floral recovery after the Cretaceous-Paleogene extinction. Important Peligran and "Carodnia" zone vertebrate fossil assemblages from coastal BNI and Peñas Coloradas exposures are likely older than previously thought and correlate to the early Torrejonian and early Tiffanian North American Land Mammal Ages, respectively.Fil: Clyde, William C.. University of New Hampshire; Estados UnidosFil: Wilf, Peter. State University of Pennsylvania; Estados UnidosFil: Iglesias, Ari. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigaciones en Biodiversidad y Medioambiente. Universidad Nacional del Comahue. Centro Regional Universidad Bariloche. Instituto de Investigaciones en Biodiversidad y Medioambiente; ArgentinaFil: Slingerland, Rudy L.. University of Pennsylvania; Estados UnidosFil: Barnum, Timothy. University of New Hampshire; Estados UnidosFil: Bijl, Peter K.. University of Utrecht; Países BajosFil: Bralower, Timothy J.. State University of Pennsylvania; Estados UnidosFil: Brinkhuis, Henk. University of Utrecht; Países BajosFil: Comer, Emily E.. State University of Pennsylvania; Estados UnidosFil: Huber, Brian T.. Smithsonian Institution; Estados UnidosFil: Ibañez Mejia, Mauricio. University of Arizona; Estados UnidosFil: Jicha, Brian R.. University of Wisconsin; Estados UnidosFil: Krause, Javier Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte; Argentina. Museo Paleontológico Egidio Feruglio; ArgentinaFil: Schuet, Jonathan D.. State University of Pennsylvania; Estados UnidosFil: Singer, Bradley S.. University of Wisconsin; Estados UnidosFil: Raigemborn, María Sol. Universidad Nacional de La Plata; ArgentinaFil: Schmitz, Mark D.. University of Idaho; Estados UnidosFil: Sluijs, Appy. University of Utrecht; Países BajosFil: Zamaloa, María del Carmen. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Ecología, Genética y Evolución; Argentin

Initiation and Characterization of Small Cell Lung Cancer Patient-Derived Xenografts from Ultrasound-Guided Transbronchial Needle Aspirates

<div><p>Small cell lung cancer (SCLC) is a devastating disease with limited treatment options. Due to its early metastatic nature and rapid growth, surgical resection is rare. Standard of care treatment regimens remain largely unchanged since the 1980’s, and five-year survival lingers near 5%. Patient-derived xenograft (PDX) models have been established for other tumor types, amplifying material for research and serving as models for preclinical experimentation; however, limited availability of primary tissue has curtailed development of these models for SCLC. The objective of this study was to establish PDX models from commonly collected fine needle aspirate biopsies of primary SCLC tumors, and to assess their utility as research models of primary SCLC tumors. These transbronchial needle aspirates efficiently engrafted as xenografts, and tumor histomorphology was similar to primary tumors. Resulting tumors were further characterized by H&E and immunohistochemistry, cryopreserved, and used to propagate tumor-bearing mice for the evaluation of standard of care chemotherapy regimens, to assess their utility as models for tumors in SCLC patients. When treated with Cisplatin and Etoposide, tumor-bearing mice responded similarly to patients from whom the tumors originated. Here, we demonstrate that PDX tumor models can be efficiently established from primary SCLC transbronchial needle aspirates, even after overnight shipping, and that resulting xenograft tumors are similar to matched primary tumors in cancer patients by both histology and chemo-sensitivity. This method enables physicians at non-research institutions to collaboratively contribute to the rapid establishment of extensive PDX collections of SCLC, enabling experimentation with clinically relevant tissues and development of improved therapies for SCLC patients.</p></div

PDX response to P/E <i>in vivo</i> generally reflects clinical response.

<p>Upon reaching a mean tumor volume of 150–200 mm³, mice bearing A) LU073p2 or B) LU086p3 PDX tumors were randomized, administered either vehicle (closed triangles) or P/E (open circles; 5 mg/kg Cisplatin on day 1 and 8 mg/kg Etoposide on days 1, 2 & 3 of treatment), and tumors were measured weekly. The bracket indicates the time to progression (TTP). C) The mean TTP of PDX tumors following one course of P/E treatment was plotted versus observed clinical TTP. Data is represented as Mean ± SEM and reflects cohorts of n = 5 mice per group.</p

Immunohistochemical Staining of Diagnostic Lung Cancer Markers.

<p>Immunohistochemical Staining of Diagnostic Lung Cancer Markers.</p

PDX Growth & P/E Responsiveness.

<p>PDX Growth & P/E Responsiveness.</p

Expression of SCLC antigens is maintained in PDX tumor models.

<p>FFPE sections were prepared from PDX tumors (LU086p1 is represented). (A) Tissue sections were stained by IHC for diagnostic SCLC markers Chromagranin A (CHGA), Synaptophysin (SYP), or CD56. Scale bars represent 10um. (B) Tissue sections were stained by IHC for diagnostic non-SCLC markers Keratin 5 (KRT5), Keratin 6 (KRT6A), Keratin 7 (KRT7), Keratin 14 (KRT14), Keratin 20 (KRT20), Napsin A (NAPSA), TP63, or TTF1. Scale bars represent 10um. (C) PDX tumor cells were dissociated into single-cell suspensions and analyzed by flow cytometry for expression of EpCAM (CD326) and NCAM1 (CD56). Histograms displaying expression levels are shown (dark black line), whereas background signal was determined using a matched isotype control antibody (filled gray).</p

Activation of the Jak3 pathway is associated with granulocytic differentiation of myeloid precursor cells

Jak3, a member of the Janus kinase family of cytoplasmic tyrosine kinases, is expressed at low levels in immature hematopoietic cells and its expression is dramatically up-regulated during the terminal differentiation of these cells. To better understand the role of Jak3 in myeloid cell development, we have investigated the role of Jak3 in myeloid cell differentiation using the 32Dcl3 cell system. Our studies show that Jak3 is a primary response gene for granulocyte colony-stimulating factor (G-CSF) and the accumulation of tyrosine phosphorylated Jak3 correlated with cell growth inhibition and terminal granulocytic differentiation in response to G-CSF. Ectopic overexpression of Jak3 in 32Dcl3 cells resulted in an acceleration of the G-CSF-induced differentiation program that was preceded by G1 cell cycle arrest, which was associated with the up-regulation of the cyclin-dependent kinase inhibitor p27Kip1 and down-regulation of Cdk2, Cdk4, Cdk6, and Cyclin E. In addition, ectopic over-expression of Jak3 appears to result in the inactivation of PKB/Akt and Stat3- mediated proliferative pathways in the presence of G-CSF. Similarly, overexpression of Jak3 in primary bone marrow cells resulted in an acceleration of granulocytic differentiation in the presence of granulocyte-macrophage colony-stimulating factor, which was associated with their growth arrest in the G1 phase of the cell cycle. Taken together, these results indicate that Jak3-mediated signals play an important role in myeloid cell differentiation. © 2002 by The American Society of Hematology.link_to_OA_fulltex