13 research outputs found
Empirical Model for the Variarion in Concentration of Metal Ions During a Precipitation Event
The concentration of a pollutant in an air mass and the concentration of that pollutant in a series of rain water samples from a single event within that air mass, fluctuate during the course of the event. This the result of scavenging, diffusion, and advection processes. A simple mathematical model, containing only a scavenging term has had limited success in describing changes of concentration in rain water. To date, no attempt has been made to include diffusion or advection terms in the model. In this study, a two factor model was developed after determining that (1) the exponential scavenging term is dependent upon the amount of precipitation that has fallen rather than time elapsed and (2) that the magnitude of the diffusion/advection term is inversely proportional to the precipitation rate. Coefficients for the variables in the two terms [Psiav and (bCf), respectively] were determined by the best fit of concentration curve derived from the model equation to experimental points. Time series from 24 rain events samples collected during 1987-88 and during the spring of 1998 were analyzed. The values of Psiav were remarkably constant during both periods, but the two groups of Psiav were different. The values of (bCf) correlated moderately well with the concentrations of ions in the samples
Guide to Cataloging DVD and Blu-ray Discs Using AACR2r and MARC 21 2008 Update
This guide is intended as an update to the 2002 Guide to Cataloging DVDs UsingAACR2r Chapters 7 and 9 created by the DVD Cataloging Task Force of OLAC. The update incorporates rule changes and interpretations that resulted from the 2004 Amendments for Chapters 7 and 9 of Anglo-American Cataloguing Rules (AACR2) and expands the discussion of formats to include Blu-ray Discs, DualDiscs, and DVD-Audio Discs. The information and cataloging examples presented should help clarify principles and rules used in cataloging DVD formats and digital video disc formats. There is also information to help the cataloging process for the Blu-ray Discs and DVD-Audio, newer formats that libraries will begin and continue to purchase as producers market and develop them for consumer use
Best Practices for Cataloging DVD-Video and Blu-ray Discs Using RDA and MARC21
Best Practices for Cataloging DVD-video and Blu-ray Discs Using RDA and MARC21 builds upon the work of the 2008 Guide to Cataloging DVD and Blu-ray Discs Using AACR2r and MARC21, which in turn updated the 2002 Guide to Cataloging DVDs Using AACR2r Chapters 7 and 9 created by the DVD Cataloging Task Force of OLAC.
The focus of this new document is to provide a set of “best practice” recommendations rather than a step-by-step instruction manual for cataloging DVD-video and Blu-ray Discs. One reason for this shift is that RDA cataloging practice is far from settled, particularly in regard to special format materials. Best practice recommendations will likely be easier to manage as RDA instructions evolve.
This document is intended for use with Resource Description and Access (RDA) and the MARC21 Format for Bibliographic Data. It should not be considered a substitute for the RDA Toolkit. The best practice recommendations and cataloging examples presented in the document are intended only to clarify RDA principles and instructions used in cataloging DVD-video and Blu- ray Disc formats
Best Practices for Cataloging DVD-Video and Blu-ray Discs Using RDA and MARC21 Version 1.1
Purpose
Best Practices for Cataloging DVD-video and Blu-ray Discs Using RDA and MARC21 builds upon the work of the 2008 Guide to Cataloging DVD and Blu-ray Discs Using AACR2r and MARC21, which in turn updated the 2002 Guide to Cataloging DVDs Using AACR2r Chapters 7 and 9 created by the DVD Cataloging Task Force of OLAC.
The focus of this new document is to provide a set of “best practice” recommendations rather than a step-by-step instruction manual for cataloging DVD-video and Blu-ray Discs. One reason for this shift is that RDA cataloging practice is far from settled, particularly in regard to special format materials. Best practice recommendations will likely be easier to manage as RDA instructions evolve.
This document is intended for use with Resource Description and Access (RDA) and the MARC21 Format for Bibliographic Data. It should not be considered a substitute for the RDA Toolkit. The best practice recommendations and cataloging examples presented in the document are intended only to clarify RDA principles and instructions used in cataloging DVD-video and Blu- ray Disc formats.
The opening section provides a general overview of DVD and Blu-ray technology, disc characteristics, plus a comparison with compact disc (CD) technology. A brief introduction to RDA follows, to provide a basic frame of reference for the document. Since most libraries are still encoding data in MARC21, the main part of the document is generally arranged by RDA element in the order they are encountered in a MARC21 record. Each section includes examples that reflect the principles outlined in the document. Examples use ISBD as the presentation format. A table outlining recommended description and encoding of DVD-Video and Blu-ray Disc attributes is given in the appendix. A list of resources and a selection of full MARC21 record examples illustrating common situations encountered in DVD-Video and Blu-ray Disc cataloging completes the document
Gene Expression Signature in Peripheral Blood Detects Thoracic Aortic Aneurysm
BACKGROUND: Thoracic aortic aneurysm (TAA) is usually asymptomatic and associated with high mortality. Adverse clinical outcome of TAA is preventable by elective surgical repair; however, identifying at-risk individuals is difficult. We hypothesized that gene expression patterns in peripheral blood cells may correlate with TAA disease status. Our goal was to identify a distinct gene expression signature in peripheral blood that may identify individuals at risk for TAA. METHODS AND FINDINGS: Whole genome gene expression profiles from 94 peripheral blood samples (collected from 58 individuals with TAA and 36 controls) were analyzed. Significance Analysis of Microarray (SAM) identified potential signature genes characterizing TAA vs. normal, ascending vs. descending TAA, and sporadic vs. familial TAA. Using a training set containing 36 TAA patients and 25 controls, a 41-gene classification model was constructed for detecting TAA status and an overall accuracy of 78+/-6% was achieved. Testing this classifier on an independent validation set containing 22 TAA samples and 11 controls yielded an overall classification accuracy of 78%. These 41 classifier genes were further validated by TaqMan real-time PCR assays. Classification based on the TaqMan data replicated the microarray results and achieved 80% classification accuracy on the testing set. CONCLUSIONS: This study identified informative gene expression signatures in peripheral blood cells that can characterize TAA status and subtypes of TAA. Moreover, a 41-gene classifier based on expression signature can identify TAA patients with high accuracy. The transcriptional programs in peripheral blood leading to the identification of these markers also provide insights into the mechanism of development of aortic aneurysms and highlight potential targets for therapeutic intervention. The classifier genes identified in this study, and validated by TaqMan real-time PCR, define a set of promising potential diagnostic markers, setting the stage for a blood-based gene expression test to facilitate early detection of TAA
31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two
Background
The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd.
Methods
We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background.
Results
First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001).
Conclusions
In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival
Initial On-Orbit Engineering Results from the O/OREOS Nanosatellite
The Organism/Organics Exposure to Orbital Stresses (O/OREOS) nanosatellite mission successfully launched on November 19, 2010 from Kodiak, AK aboard a Minotaur IV launch vehicle. The principal goals for this 5.5 kg spacecraft include conducting astrobiologically-relevant experiments in two separate payloads within the 3U cubesat form factor and demonstrating in-situ measurement technology in a small satellite. Developed by the Small Spacecraft Payloads and Technology Team at NASA Ames Research Center, O/OREOS builds upon heritage gained from its two predecessors, GeneSat-1 and PharmaSat. Mission operations are conducted by students at Santa Clara University using several 3-meter S-Band antennas and supporting stations, an OSCAR-class dual-Yagi UHF station, and an automated network of receive-only UHF stations located throughout the United States. This paper presents an overview of the O/OREOS mission objectives, a description of the system design, and initial results for the onorbit performance of the spacecraft and its ground segment
O/OREOS Nanosatellite: A Multi-Payload Technology Demonstration
The Organism/Organic Exposure to Orbital Stresses (O/OREOS) nanosatellite follows in the footsteps of the successful GeneSat-1 and PharmaSat missions to validate key technologies developed to conduct compelling science experiments in space for a small price tag. Developed by the Small Spacecraft Division at NASA Ames Research Center, the 5.5-kg 3U satellite contains two completely independent payloads and a novel drag-enhancing device which shortens the spacecraft’s orbital lifetime, thereby mitigating orbital debris. This paper provides an overview of the mission as well as an in-depth discussion of each payload and the de-orbit mechanism (DOM) while highlighting lessons learned from the spacecraft’s development
Identification of driver genes for critical forms of COVID-19 in a deeply phenotyped young patient cohort
International audienceThe etiopathogenesis of critical COVID-19 remains unknown. Indeed given major confounding factors (age and comorbidities), true drivers of this condition have remained elusive. Here, we employ an unprecedented multi-omics analysis, combined with artificial intelligence, in a young patient cohort where major comorbidities have been excluded at the onset. Here, we established a three-tier cohort of individuals younger than 50 years without major comorbidities. These included 47 “critical” (in the ICU under mechanical ventilation) and 25 “non-critical” (in a non-critical care ward) COVID-19 patients as well as 22 healthy individuals. The analyses included whole-genome sequencing, whole-blood RNA sequencing, plasma and blood mononuclear cells proteomics, cytokine profiling and high-throughput immunophenotyping. An ensemble of machine learning, deep learning, quantum annealing and structural causal modeling led to key findings. Critical patients were characterized by exacerbated inflammation, perturbed lymphoid/myeloid compartments, coagulation and viral cell biology. Within a unique gene signature that differentiated critical from non-critical patients, several driver genes promoted critical COVID-19 among which the upregulated metalloprotease ADAM9 was key. This gene signature was supported in a second independent cohort of 81 critical and 73 recovered COVID-19 patients, as were ADAM9 transcripts, soluble form and proteolytic activity. Ex vivo ADAM9 inhibition affected SARS-CoV-2 uptake and replication in human lung epithelial cells. In conclusion, within a young, otherwise healthy, COVID-19 cohort, we provide the landscape of biological perturbations in vivo where a unique gene signature differentiated critical from non-critical patients. The key driver, ADAM9, interfered with SARS-CoV-2 biology. A repositioning strategy for anti-ADAM9 therapeutic is feasible