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PurposeTo assess the safety and efficacy of the third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor osimertinib as neoadjuvant therapy in patients with surgically resectable stage I-IIIA EGFR-mutated non-small cell lung cancer (NSCLC).Patients and methodsThis was a multi-institutional phase II trial of neoadjuvant osimertinib for patients with surgically resectable stage I-IIIA (American Joint Committee on Cancer [AJCC] V7) EGFR-mutated (L858R or exon 19 deletion) NSCLC (ClinicalTrials.gov identifier: NCT03433469). Patients received osimertinib 80 mg orally once daily for up to two 28-day cycles before surgical resection. The primary end point was major pathological response (MPR) rate. Secondary safety and efficacy end points were also assessed. Exploratory end points included pretreatment and post-treatment tumor mutation profiling.ResultsA total of 27 patients were enrolled and treated with neoadjuvant osimertinib for a median 56 days before surgical resection. Twenty-four (89%) patients underwent subsequent surgery; three (11%) patients were converted to definitive chemoradiotherapy. The MPR rate was 14.8% (95% CI, 4.2 to 33.7). No pathological complete responses were observed. The ORR was 52%, and the median DFS was 40.9 months. One treatment-related serious adverse event (AE) occurred (3.7%). No patients were unable to undergo surgical resection or had surgery delayed because of an AE. The most common co-occurring tumor genomic alterations were in TP53 (42%) and RBM10 (21%).ConclusionTreatment with neoadjuvant osimertinib in surgically resectable (stage IA-IIIA, AJCC V7) EGFR-mutated NSCLC did not meet its primary end point for MPR rate. However, neoadjuvant osimertinib did not lead to unanticipated AEs, surgical delays, nor result in a significant unresectability rate.

Chimeric antigen receptor (CAR) T cells are ineffective against solid tumors with immunosuppressive microenvironments. To overcome suppression, we engineered circuits in which tumor-specific synNotch receptors locally induce production of the cytokine IL-2. These circuits potently enhance CAR T cell infiltration and clearance of immune-excluded tumors, without systemic toxicity. The most effective IL-2 induction circuit acts in an autocrine and T cell receptor (TCR)- or CAR-independent manner, bypassing suppression mechanisms including consumption of IL-2 or inhibition of TCR signaling. These engineered cells establish a foothold in the target tumors, with synthetic Notch-induced IL-2 production enabling initiation of CAR-mediated T cell expansion and cell killing. Thus, it is possible to reconstitute synthetic T cell circuits that activate the outputs ultimately required for an antitumor response, but in a manner that evades key points of tumor suppression.

Immunological targeting of pathological cells has been successful in oncology and is expanding to other pathobiological contexts. Here, we present a flexible platform that allows labeling cells of interest with the surface-expressed model antigen ovalbumin (OVA), which can be eliminated via either antigen-specific T cells or newly developed OVA antibodies. We demonstrate that hepatocytes can be effectively targeted by either modality. In contrast, pro-fibrotic fibroblasts associated with pulmonary fibrosis are only eliminated by T cells in initial experiments, which reduced collagen deposition in a fibrosis model. This new experimental platform will facilitate development of immune-based approaches to clear potential pathological cell types in vivo.

Living cells often identify their correct partner or target cells by integrating information from multiple receptors, achieving levels of recognition that are difficult to obtain with individual molecular interactions. In this study, we engineered a diverse library of multireceptor cell-cell recognition circuits by using synthetic Notch receptors to transcriptionally interconnect multiple molecular recognition events. These synthetic circuits allow engineered T cells to integrate extra- and intracellular antigen recognition, are robust to heterogeneity, and achieve precise recognition by integrating up to three different antigens with positive or negative logic. A three-antigen AND gate composed of three sequentially linked receptors shows selectivity in vivo, clearing three-antigen tumors while ignoring related two-antigen tumors. Daisy-chaining multiple molecular recognition events together in synthetic circuits provides a powerful way to engineer cellular-level recognition.

UnlabelledRegionally distinct wine characteristics (terroir) are an important aspect of wine production and consumer appreciation. Microbial activity is an integral part of wine production, and grape and wine microbiota present regionally defined patterns associated with vineyard and climatic conditions, but the degree to which these microbial patterns associate with the chemical composition of wine is unclear. Through a longitudinal survey of over 200 commercial wine fermentations, we demonstrate that both grape microbiota and wine metabolite profiles distinguish viticultural area designations and individual vineyards within Napa and Sonoma Counties, California. Associations among wine microbiota and fermentation characteristics suggest new links between microbiota, fermentation performance, and wine properties. The bacterial and fungal consortia of wine fermentations, composed from vineyard and winery sources, correlate with the chemical composition of the finished wines and predict metabolite abundances in finished wines using machine learning models. The use of postharvest microbiota as an early predictor of wine chemical composition is unprecedented and potentially poses a new paradigm for quality control of agricultural products. These findings add further evidence that microbial activity is associated with wine terroirImportanceWine production is a multi-billion-dollar global industry for which microbial control and wine chemical composition are crucial aspects of quality. Terroir is an important feature of consumer appreciation and wine culture, but the many factors that contribute to terroir are nebulous. We show that grape and wine microbiota exhibit regional patterns that correlate with wine chemical composition, suggesting that the grape microbiome may influence terroir In addition to enriching our understanding of how growing region and wine properties interact, this may provide further economic incentive for agricultural and enological practices that m

UnlabelledRegionally distinct wine characteristics (terroir) are an important aspect of wine production and consumer appreciation. Microbial activity is an integral part of wine production, and grape and wine microbiota present regionally defined patterns associated with vineyard and climatic conditions, but the degree to which these microbial patterns associate with the chemical composition of wine is unclear. Through a longitudinal survey of over 200 commercial wine fermentations, we demonstrate that both grape microbiota and wine metabolite profiles distinguish viticultural area designations and individual vineyards within Napa and Sonoma Counties, California. Associations among wine microbiota and fermentation characteristics suggest new links between microbiota, fermentation performance, and wine properties. The bacterial and fungal consortia of wine fermentations, composed from vineyard and winery sources, correlate with the chemical composition of the finished wines and predict metabolite abundances in finished wines using machine learning models. The use of postharvest microbiota as an early predictor of wine chemical composition is unprecedented and potentially poses a new paradigm for quality control of agricultural products. These findings add further evidence that microbial activity is associated with wine terroirImportanceWine production is a multi-billion-dollar global industry for which microbial control and wine chemical composition are crucial aspects of quality. Terroir is an important feature of consumer appreciation and wine culture, but the many factors that contribute to terroir are nebulous. We show that grape and wine microbiota exhibit regional patterns that correlate with wine chemical composition, suggesting that the grape microbiome may influence terroir In addition to enriching our understanding of how growing region and wine properties interact, this may provide further economic incentive for agricultural and enological practices that m

Regionally distinct wine characteristics (terroir) are an important aspect of wine production and consumer appreciation. Microbial activity is an integral part of wine production, and grape and wine microbiota present regionally defined patterns associated with vineyard and climatic conditions, but the degree to which these microbial patterns associate with the chemical composition of wine is unclear. Through a longitudinal survey of over 200 commercial wine fermentations, we demonstrate that both grape microbiota and wine metabolite profiles distinguish viticultural area designations and individual vineyards within Napa and Sonoma Counties, California. Associations among wine microbiota and fermentation characteristics suggest new links between microbiota, fermentation performance, and wine properties. The bacterial and fungal consortia of wine fermentations, composed from vineyard and winery sources, correlate with the chemical composition of the finished wines and predict metabolite abundances in finished wines using machine learning models. The use of postharvest microbiota as an early predictor of wine chemical composition is unprecedented and potentially poses a new paradigm for quality control of agricultural products. These findings add further evidence that microbial activity is associated with wine terroir Wine production is a multi-billion-dollar global industry for which microbial control and wine chemical composition are crucial aspects of quality. Terroir is an important feature of consumer appreciation and wine culture, but the many factors that contribute to terroir are nebulous. We show that grape and wine microbiota exhibit regional patterns that correlate with wine chemical composition, suggesting that the grape microbiome may influence terroir In addition to enriching our understanding of how growing region and wine properties interact, this may provide further economic incentive for agricultural and enological practices that maintain regional mi

Noble rot results from exceptional infections of ripe grape (Vitis vinifera) berries by Botrytis cinerea. Unlike bunch rot, noble rot promotes favorable changes in grape berries and the accumulation of secondary metabolites that enhance wine grape composition. Noble rot-infected berries of cv Sémillon, a white-skinned variety, were collected over 3 years from a commercial vineyard at the same time that fruit were harvested for botrytized wine production. Using an integrated transcriptomics and metabolomics approach, we demonstrate that noble rot alters the metabolism of cv Sémillon berries by inducing biotic and abiotic stress responses as well as ripening processes. During noble rot, B. cinerea induced the expression of key regulators of ripening-associated pathways, some of which are distinctive to the normal ripening of red-skinned cultivars. Enhancement of phenylpropanoid metabolism, characterized by a restricted flux in white-skinned berries, was a common outcome of noble rot and red-skinned berry ripening. Transcript and metabolite analyses together with enzymatic assays determined that the biosynthesis of anthocyanins is a consistent hallmark of noble rot in cv Sémillon berries. The biosynthesis of terpenes and fatty acid aroma precursors also increased during noble rot. We finally characterized the impact of noble rot in botrytized wines. Altogether, the results of this work demonstrated that noble rot causes a major reprogramming of berry development and metabolism. This desirable interaction between a fruit and a fungus stimulates pathways otherwise inactive in white-skinned berries, leading to a greater accumulation of compounds involved in the unique flavor and aroma of botrytized wines.

Noble rot results from exceptional infections of ripe grape (Vitis vinifera) berries by Botrytis cinerea. Unlike bunch rot, noble rot promotes favorable changes in grape berries and the accumulation of secondary metabolites that enhance wine grape composition. Noble rot-infected berries of cv Sémillon, a white-skinned variety, were collected over 3 years from a commercial vineyard at the same time that fruit were harvested for botrytized wine production. Using an integrated transcriptomics and metabolomics approach, we demonstrate that noble rot alters the metabolism of cv Sémillon berries by inducing biotic and abiotic stress responses as well as ripening processes. During noble rot, B. cinerea induced the expression of key regulators of ripening-associated pathways, some of which are distinctive to the normal ripening of red-skinned cultivars. Enhancement of phenylpropanoid metabolism, characterized by a restricted flux in white-skinned berries, was a common outcome of noble rot and red-skinned berry ripening. Transcript and metabolite analyses together with enzymatic assays determined that the biosynthesis of anthocyanins is a consistent hallmark of noble rot in cv Sémillon berries. The biosynthesis of terpenes and fatty acid aroma precursors also increased during noble rot. We finally characterized the impact of noble rot in botrytized wines. Altogether, the results of this work demonstrated that noble rot causes a major reprogramming of berry development and metabolism. This desirable interaction between a fruit and a fungus stimulates pathways otherwise inactive in white-skinned berries, leading to a greater accumulation of compounds involved in the unique flavor and aroma of botrytized wines.

Noble rot results from exceptional infections of ripe grape (Vitis vinifera) berries by Botrytis cinerea. Unlike bunch rot, noble rot promotes favorable changes in grape berries and the accumulation of secondary metabolites that enhance wine grape composition. Noble rot-infected berries of cv Sémillon, a white-skinned variety, were collected over 3 years from a commercial vineyard at the same time that fruit were harvested for botrytized wine production. Using an integrated transcriptomics and metabolomics approach, we demonstrate that noble rot alters the metabolism of cv Sémillon berries by inducing biotic and abiotic stress responses as well as ripening processes. During noble rot, B. cinerea induced the expression of key regulators of ripening-associated pathways, some of which are distinctive to the normal ripening of red-skinned cultivars. Enhancement of phenylpropanoid metabolism, characterized by a restricted flux in white-skinned berries, was a common outcome of noble rot and red-skinned berry ripening. Transcript and metabolite analyses together with enzymatic assays determined that the biosynthesis of anthocyanins is a consistent hallmark of noble rot in cv Sémillon berries. The biosynthesis of terpenes and fatty acid aroma precursors also increased during noble rot. We finally characterized the impact of noble rot in botrytized wines. Altogether, the results of this work demonstrated that noble rot causes a major reprogramming of berry development and metabolism. This desirable interaction between a fruit and a fungus stimulates pathways otherwise inactive in white-skinned berries, leading to a greater accumulation of compounds involved in the unique flavor and aroma of botrytized wines.

Botrytized wines are produced from grape berries infected by Botrytis cinerea under specific environmental conditions. Here, we report the draft genome sequence of B. cinerea BcDW1, a strain isolated from Sémillon grapes in Napa Valley in 1992 that is used with the intent to induce noble rot for botrytized wine production.

Botrytized wines are produced from grape berries infected by Botrytis cinerea under specific environmental conditions. Here, we report the draft genome sequence of B. cinerea BcDW1, a strain isolated from Sémillon grapes in Napa Valley in 1992 that is used with the intent to induce noble rot for botrytized wine production.

While wine fermentation has long been known to involve complex microbial communities, the composition and role of bacteria other than a select set of lactic acid bacteria (LAB) has often been assumed either negligible or detrimental. This study served as a pilot study for using barcoded amplicon next-generation sequencing to profile bacterial community structure in wines and grape musts, comparing the taxonomic depth achieved by sequencing two different domains of prokaryotic 16S rDNA (V4 and V5). This study was designed to serve two goals: 1) to empirically determine the most taxonomically informative 16S rDNA target region for barcoded amplicon sequencing of wine, comparing V4 and V5 domains of bacterial 16S rDNA to terminal restriction fragment length polymorphism (TRFLP) of LAB communities; and 2) to explore the bacterial communities of wine fermentation to better understand the biodiversity of wine at a depth previously unattainable using other techniques. Analysis of amplicons from the V4 and V5 provided similar views of the bacterial communities of botrytized wine fermentations, revealing a broad diversity of low-abundance taxa not traditionally associated with wine, as well as atypical LAB communities initially detected by TRFLP. The V4 domain was determined as the more suitable read for wine ecology studies, as it provided greater taxonomic depth for profiling LAB communities. In addition, targeted enrichment was used to isolate two species of Alphaproteobacteria from a finished fermentation. Significant differences in diversity between inoculated and uninoculated samples suggest that Saccharomyces inoculation exerts selective pressure on bacterial diversity in these fermentations, most notably suppressing abundance of acetic acid bacteria. These results determine the bacterial diversity of botrytized wines to be far higher than previously realized, providing further insight into the fermentation dynamics of these wines, and demonstrate the utility of next

While wine fermentation has long been known to involve complex microbial communities, the composition and role of bacteria other than a select set of lactic acid bacteria (LAB) has often been assumed either negligible or detrimental. This study served as a pilot study for using barcoded amplicon next-generation sequencing to profile bacterial community structure in wines and grape musts, comparing the taxonomic depth achieved by sequencing two different domains of prokaryotic 16S rDNA (V4 and V5). This study was designed to serve two goals: 1) to empirically determine the most taxonomically informative 16S rDNA target region for barcoded amplicon sequencing of wine, comparing V4 and V5 domains of bacterial 16S rDNA to terminal restriction fragment length polymorphism (TRFLP) of LAB communities; and 2) to explore the bacterial communities of wine fermentation to better understand the biodiversity of wine at a depth previously unattainable using other techniques. Analysis of amplicons from the V4 and V5 provided similar views of the bacterial communities of botrytized wine fermentations, revealing a broad diversity of low-abundance taxa not traditionally associated with wine, as well as atypical LAB communities initially detected by TRFLP. The V4 domain was determined as the more suitable read for wine ecology studies, as it provided greater taxonomic depth for profiling LAB communities. In addition, targeted enrichment was used to isolate two species of Alphaproteobacteria from a finished fermentation. Significant differences in diversity between inoculated and uninoculated samples suggest that Saccharomyces inoculation exerts selective pressure on bacterial diversity in these fermentations, most notably suppressing abundance of acetic acid bacteria. These results determine the bacterial diversity of botrytized wines to be far higher than previously realized, providing further insight into the fermentation dynamics of these wines, and demonstrate the utility of next

Joan Flasch Artists' Book Collection

Joan Flasch Artists' Book Collection

We report on the design, fabrication, and on-sky performance of the Florida Image Slicer for Infrared Cosmology and Astrophysics (FISICA)- a fully-cryogenic all-reflective image-slicing integral field unit for the FLAMINGOS near-infrared spectrograph. Designed to accept input beams near f/15, FISICA with FLAMINGOS provides R \sim 1300 spectra over a 16x33-arcsec field-of-view on the Cassegrain f/15 focus of the KPNO 4-meter telescope, or a 6x12-arcsec field-of-view on the Nasmyth or Bent Cassegrain foci of the Gran Telescopio Canarias 10.4-meter telescope. FISICA accomplishes this using three sets of "monolithic" powered mirror arrays, each with 22 mirrored surfaces cut into a single piece of aluminum. We review the optical and opto-mechanical design and fabrication of FISICA, as well as laboratory test results for FISICA integrated with the FLAMINGOS instrument. Finally, we present performance results from observations with FISICA at the KPNO 4-m telescope and comparisons of FISICA performance to other available IFUs on 4-m to 8-m-class telescopes., Comment: Submitted to SPIE Astronomical Telescopes and Instrumentation; 8 pages, incl. color figures

We report on the design, fabrication, and on-sky performance of the Florida Image Slicer for Infrared Cosmology and Astrophysics (FISICA)- a fully-cryogenic all-reflective image-slicing integral field unit for the FLAMINGOS near-infrared spectrograph. Designed to accept input beams near f/15, FISICA with FLAMINGOS provides R \sim 1300 spectra over a 16x33-arcsec field-of-view on the Cassegrain f/15 focus of the KPNO 4-meter telescope, or a 6x12-arcsec field-of-view on the Nasmyth or Bent Cassegrain foci of the Gran Telescopio Canarias 10.4-meter telescope. FISICA accomplishes this using three sets of "monolithic" powered mirror arrays, each with 22 mirrored surfaces cut into a single piece of aluminum. We review the optical and opto-mechanical design and fabrication of FISICA, as well as laboratory test results for FISICA integrated with the FLAMINGOS instrument. Finally, we present performance results from observations with FISICA at the KPNO 4-m telescope and comparisons of FISICA performance to other available IFUs on 4-m to 8-m-class telescopes., Comment: Submitted to SPIE Astronomical Telescopes and Instrumentation; 8 pages, incl. color figures

The Parallel Evaluation and Experimentation Platform (PEEP) is the result of an effort at Rome Laboratory to identify the most promising general- purpose software development tools, techniques and approaches from industry and academia for programming high performance parallel computers to meet the needs of Command and Control (C2) applications. The PEEP is a prototype platform for evaluating the applicability of results from parallel programming research efforts to improve the productivity of designers and developers. Intermetrics conducted a study of available innovative tools and techniques beginning in early 1990. From the survey, Intermetrics chose candidates for inclusion on a prototype platform, and began to install and evaluate the chosen components. With the prototype PEEP, a number of case studies were conducted to develop small parallel programs using the selected tools. The purpose of these case studies was not to advance the state of the art in parallel algorithms, but to exercise the tools collected for the prototype PEEP. This work identified requirements on architectures, life cycle activities and technologies to support parallel development and developed a long range plan for the PEEP. The conclusions from these case studies also suggest useful methodologies for developing parallel software, and have led to recommendations based on the performance of the current tools and on the projected needs of parallel software development.

Electrical guardband testing of microcircuits in lieu of 100% testing at the device temperature extremes has long been championed by device manufacturers as a cost effective means of guaranteeing reliable device performance in military systems. This report describes a detailed study of the validity of the guardbanding concept and the effects of manufacturer, datecode, and reliability grade upon these devices. Through the utilization of intensive testing techniques in conjunction with the development of a series of linear, log-linear, and exponential mathematical models a high degree of guardband test limit validity was established. Further analysis of the data utilizing advanced statistical techniques resulted in the development of a method for accurately setting guardband test limits on most parameters. Additional correlation analysis was performed on the test samples resulting in the establishment of the interchangeabiliy of JAN, 883B processed, and commerical devices. (Author)

Color; 41 minutes, 39 seconds. Summary: Greg Allen discusses recent University initiatives to increase security and safety on campus, and what the University is going to continue to do in the future to maintain the University's high standard of safety and staff awareness.

8 p., ill., Vol. 2 No. 1, August 2006; The Sculpture of Les Bruning; Technology Professor of the Year; Publications; Leadership; Conference Presentations; New Book; Speaking Engagements; Conference Workshops; BU Art Faculty Exhibit; Promotions; Conferences; Review Boards; Community Ties; Research in Progress; Book Reviews; Heard in the News....; Did You Know That....?; A Big Welcome to Our New Faculty Members!; Organizations; Certifications; Writing Project Workshop; First Two Faculty Forums 2006: September Film Forum: Paths of Glory, October Book Forum

10 p., ill., Vol. 8 No. 1, March 2013; Sally Bitzinger: Beloved Faculty Devotee; Mary Hawkins Selected 2011-2012 Business Leader of the Year; Publications; Conference Presentations; Conferences; Carolyn Youssef awarded Ada and James Redding, Jr. Chair of Business; Advisory Boards; Speaking Engagements; Matt Crosston awarded the Miller Chair for Industrial and International Security; Did You Know That...?; And the winners are...; Rod Hewlett awarded the Grewcock Chair for American Vision and Values; Review Boards; Certifications; Community Ties; Welcome to Our New Faculty Members!

12 p., ill., Vol. 5 No. 1, February 2010; Award for Excellence; Publications; New Book; Conference Presentations; New Editor of JBAM; Workshops; Leadership; Conferences; Poetry Reading; Community Ties; Organizations; Review Boards; Research in Progress; Welcome to our New Faculty Members!; Speaking Engagements; Curriculum Development; Did You Know That...?; Welcome to our New Administrators!: Congratulations to President Mary Hawkins, Welcome Martha Munoz, Congratulations Vice President Donna McDaniel, Welcome Rod Hewlett, Congratulations Mary Dobransky, Congratulations Carole Patrick, Welcome Cathy Heffernan

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8 p., ill., Vol. 3 No. 1, February 2008; Pinnacle Award Academic Achievement; Publications; Conference Presentations; Speaking Engagements; Conferences; Leadership; Review Boards; China-USA Forum on Distance Education; Faculty Focus; Education in Progress; Community Ties; Did you Know That...?; Curriculum Development; Professional Organizations; Heard in the News...; Welcome to our New Faculty Members!

16 p., ill., Vol. 9 No. 1, March 2014; How Worms, Pride, and Politics Lead to Simple Science: John Kyndt; Carolyn Youssef-Morgan Delivers Keynote Address in Aland, Finland; Publications; Outstanding Instructor Award; Faculty Mentor Award; Conference Presentations; Workshops; Leadership; Exhibitions; Speaking Engagements; Conferences; Student Affairs; Did You Know That...?; Congratulations Clif Mason; Review Boards; Del Stites Remembers When Bellevue College Was 4-Years-Old; In Memoriam; Community Ties; Welcome to Our New Faculty Members!

8 p., ill., Vol. 7 No. 1, June 2012; Teaching in Croatia; Omaha AMA Pinnacle Award for Marketing Research; Publications; Conference Presentations; New Books; Conferences; Review Boards; In Memoriam; New Editor of JEBE; Leadership; Did You Know That...?; Speaking Engagements; Adrian4Nebraska; Certifications; Advisory Boards; Community Ties; Welcome to our New Faculty Members!