90 research outputs found

    An Analysis of Upwork Profiles: Visualizing Characteristics of Gig Workers using Digital Platform

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    In the transitional period of manual and algorithmic hiring, there has been an explosion of new employment opportunities. As a result of the ubiquity of mobile communication technologies, a gig economy has emerged which champions digital platforms as a solution to meet the burgeoning demand for on-demand workers, frequently called independent contractors or freelancers, by hiring organizations. Visualizations and linear regression are used to study information-rich Upwork profiles to determine variables that could predict how users maneuver in the gig economy. A typology of existing gig workers’ motivations is combined with visualizations to better understand the situation of the typical gig economy worker.Master of Science in Information Scienc

    Antenna Group Delay Variation Bias Effect on Advanced RAIM

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    This paper investigates the impact of the range error caused by the antenna group delay variations (noted as AGDV) on the advanced receiver autonomous integrity monitoring (ARAIM). The new multipath and AGDV error models for aviation use of new GPS and Galileo signals developed within the Dual Frequency Multipath Model for Aviation (DUFMAN) project and relevant AGDV measurements analyzed in DUFMAN [1], [2] are applied for the assessment of the impact. In this work, several approaches are taken to address the contribution of the AGDV error in the current ARAIM airborne algorithm: consideration of the user antenna bias error as a measurement bias term or as a random process sigma term. We performed ARAIM service volume simulations for Localizer Performance with Vertical guidance (LPV)-200 by applying the proposed error modeling methodologies and integrity support message (ISM) parameters in line with the current ARAIM framework. We compared availability performances as well as protection levels between the methods. It was found that 99.5% LPV-200 availability increased by approximately 5% when the newly derivedDUFMAN multipath and AGDV error models were applied. On the other hand, despite the maximum improvement of roughly one meter in the vertical protection level, the AGDV effect considered as the bias term in the worst-case sense appears to be marginal to the ARAIM availability performance

    Heterodimerization of Glycosylated Insulin-Like Growth Factor-1 Receptors and Insulin Receptors in Cancer Cells Sensitive to Anti-IGF1R Antibody

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    Identification of predictive biomarkers is essential for the successful development of targeted therapy. Insulin-like growth factor 1 receptor (IGF1R) has been examined as a potential therapeutic target for various cancers. However, recent clinical trials showed that anti-IGF1R antibody and chemotherapy are not effective for treating lung cancer.In order to define biomarkers for predicting successful IGF1R targeted therapy, we evaluated the anti-proliferation effect of figitumumab (CP-751,871), a humanized anti-IGF1R antibody, against nine gastric and eight hepatocellular cancer cell lines. Out of 17 cancer cell lines, figitumumab effectively inhibited the growth of three cell lines (SNU719, HepG2, and SNU368), decreased p-AKT and p-STAT3 levels, and induced G 1 arrest in a dose-dependent manner. Interestingly, these cells showed co-overexpression and altered mobility of the IGF1R and insulin receptor (IR). Immunoprecipitaion (IP) assays and ELISA confirmed the presence of IGF1R/IR heterodimeric receptors in figitumumab-sensitive cells. Treatment with figitumumab led to the dissociation of IGF1-dependent heterodimeric receptors and inhibited tumor growth with decreased levels of heterodimeric receptors in a mouse xenograft model. We next found that both IGF1R and IR were N-linked glyosylated in figitumumab-sensitive cells. In particular, mass spectrometry showed that IGF1R had N-linked glycans at N913 in three figitumumab-sensitive cell lines. We observed that an absence of N-linked glycosylation at N913 led to a lack of membranous localization of IGF1R and figitumumab insensitivity.The data suggest that the level of N-linked glycosylated IGF1R/IR heterodimeric receptor is highly associated with sensitivity to anti-IGF1R antibody in cancer cells

    A Scalable System for Production of Functional Pancreatic Progenitors from Human Embryonic Stem Cells

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    Development of a human embryonic stem cell (hESC)-based therapy for type 1 diabetes will require the translation of proof-of-principle concepts into a scalable, controlled, and regulated cell manufacturing process. We have previously demonstrated that hESC can be directed to differentiate into pancreatic progenitors that mature into functional glucose-responsive, insulin-secreting cells in vivo. In this study we describe hESC expansion and banking methods and a suspension-based differentiation system, which together underpin an integrated scalable manufacturing process for producing pancreatic progenitors. This system has been optimized for the CyT49 cell line. Accordingly, qualified large-scale single-cell master and working cGMP cell banks of CyT49 have been generated to provide a virtually unlimited starting resource for manufacturing. Upon thaw from these banks, we expanded CyT49 for two weeks in an adherent culture format that achieves 50–100 fold expansion per week. Undifferentiated CyT49 were then aggregated into clusters in dynamic rotational suspension culture, followed by differentiation en masse for two weeks with a four-stage protocol. Numerous scaled differentiation runs generated reproducible and defined population compositions highly enriched for pancreatic cell lineages, as shown by examining mRNA expression at each stage of differentiation and flow cytometry of the final population. Islet-like tissue containing glucose-responsive, insulin-secreting cells was generated upon implantation into mice. By four- to five-months post-engraftment, mature neo-pancreatic tissue was sufficient to protect against streptozotocin (STZ)-induced hyperglycemia. In summary, we have developed a tractable manufacturing process for the generation of functional pancreatic progenitors from hESC on a scale amenable to clinical entry

    Software for the frontiers of quantum chemistry:An overview of developments in the Q-Chem 5 package

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    This article summarizes technical advances contained in the fifth major release of the Q-Chem quantum chemistry program package, covering developments since 2015. A comprehensive library of exchange–correlation functionals, along with a suite of correlated many-body methods, continues to be a hallmark of the Q-Chem software. The many-body methods include novel variants of both coupled-cluster and configuration-interaction approaches along with methods based on the algebraic diagrammatic construction and variational reduced density-matrix methods. Methods highlighted in Q-Chem 5 include a suite of tools for modeling core-level spectroscopy, methods for describing metastable resonances, methods for computing vibronic spectra, the nuclear–electronic orbital method, and several different energy decomposition analysis techniques. High-performance capabilities including multithreaded parallelism and support for calculations on graphics processing units are described. Q-Chem boasts a community of well over 100 active academic developers, and the continuing evolution of the software is supported by an “open teamware” model and an increasingly modular design

    Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

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    Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

    31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

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    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

    Integrity Risk under Temporal Correlation for Horizontal ARAIM (H-ARAIM)

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    Integrity requirements for safety-critical Global Navigation Satellite System (GNSS) applications, such as in civil aviation for the non-precision approach through precision approach, are defined in a per hour or per approach (i.e., 150s) basis by the International Civil Aviation Organization (ICAO). This paper presents a novel methodology for mapping of such operational requirements to the specific risk at an algorithmic level for advanced receiver autonomous integrity monitoring (ARAIM), in particular horizontal ARAIM (H-ARAIM). We thoroughly evaluated the actual risk over time by performing extensive first-order Gauss Markov Process Monte Carlo runs for the propagation of time-correlated position errors and test statistics over one hour exposure time and accounting for multiple events of loss of integrity over the time interval. A comparison of the risk over time and the risk for a single epoch leads to the number of effectively independent samples. The current integrity equation was modified using the number such that specific risk requirement is allocated to a single sample for the determination of the protection level (PL). This study also examined the impact of the modified risk allocation on the existing fault detection and exclusion (FDE) algorithm by conducting H-ARAIM availability simulations and by comparing the results based on the newly proposed method with that obtained using the existing single sample-based risk allocation. In our preliminary assessment, little impact on the global availability (availability loss of approximately up to 1%) of the inflated terms of the integrity equation due to the number of valid samples was found

    The Effect of Alimentary Hyperlipemia on Thrombolysis in vivo

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    Preliminary Integrity Assessment for GPS/GLONASS RAIM with Multiple Faults

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    International audienceWith the full deployment of the Russian Global Orbiting Navigation Satellite System (GLONASS), an increased number of redundant Global Navigation Satellite System (GNSS) measurements are available, which has recently drawn interest in the feasibility of GPS/GLONASS Receiver Autonomous Integrity Monitoring (RAIM). Accordingly, the design of a rigorous integrity test methodology for GPS/GLONASS receiver has been needed in developing the GPS/GLONASS Minimum Operational Performance Standards (MOPS) for GPS/GLONASS L1-only airborne equipment [1]. These standards and test procedures must be validated in order to show that they protect the user with respect to the higher level requirements of integrity and continuity relating to safety. Thus a preliminary integrity performance assessment should be taken by applying key test procedures under relevant standards and assumptions. The resulting performance could be then used as a baseline to design the appropriate integrity test methodology. If the baseline performance does not meet the integrity requirements, new test procedures for the system with multiple faults must be developed.In this paper, we propose a multiple hypothesis-based approach to test the performance of the conventional RAIM fault detection and the corresponding integrity bound against multiple failures. In particular, we investigate the resistance of GPS/GLONASS RAIM against multiple faults based on the proposed method [1-2]. We examine several failure modes: GPS dual faults, GLONASS double faults, a single GPS fault and a single GLONASS fault, GPS constellation failure and GLONASS constellation fault, and some combinations of those fault modes. For this purpose, we first determine the worst case fault, which is the most difficult to detect whilst leading to a potential positioning failure. This corresponds, for each failure, to identifying both the worst fault direction and magnitude. Next, we evaluate the maximum probability of missed detection (PMD) under each fault by finding the worst orientation of the position error distribution under the relevant worst case fault. In this step, two types of horizontal protection bound are accounted for: one based on the previously proposed multi-bias RAIM protection method [2] and the other one based on the preliminary FDE algorithm for GPS/GLONASS MOPS [1]. We compare the resulting PMD to the requirement for a single failure, as in lines with the proposed GPS/GLONASS MOPS test procedures [1]. This is to check if the protection bounds based on the current RAIM could protect the users against multiple failures. Also, we compute total probability of hazardous misleading information (PHMI) by accounting for all possible fault hypothesis and compare it with the integrity risk requirement of 10-7. In this work, all the evaluations are based on a single day and eight days which correspond to a multiple of the periods of GPS and GLONASS constellation.Based on the PMD and PHMI analysis performed, this work proposes some essential considerations on the fault detection and exclusion (FDE) algorithm such as protection bound formulation, and the integrity test procedures and assumptions for GPS/GLONASS RAIM. Furthermore, we discuss the potential of the newly proposed test method in identifying the integrity test methodology for Advance RAIM (ARAIM) receiver.This paper presents an integrity test method for GPS/GLONASS RAIM receiver and carries out integrity risk evaluations with several failure modes based on the newly proposed method. It is shown that the PMD ranges from approximately 10-6 to 10-1 throughout the world and the maximum PMD of roughly 10-1 occurs under constellation fault conditions. It indicates that the fault detection performance of the current residual based RAIM method for a pair of failures would not meet the PMD requirement of 10-4, especially under constellation faults. We also show that the current RAIM fault detection could provide worse performance for multiple correlated failures than for a single failure. In the same way, PHMI analysis for the proposed multiple failure modes is conducted. In particular, it is shown that GPS/GLONASS protection outlined in this work appears to be safe even for multiple failures when the multi-hypothesis approach is applied. This study would help to design new integrity monitoring test procedures for GPS/GLONASS L1-only airborne equipment, and may eventually lead to the identification of standards and integrity test procedures for ARAIM
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