804 research outputs found

    Ontology as Transcendental Philosophy

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    How does the critical Kant view ontology? There is no shared scholarly answer to this question. Norbert Hinske sees in the Critique of Pure Reason a “farewell to ontology,” albeit one that took Kant long to bid (Hinske 2009). Karl Ameriks has found evidence in Kant’s metaphysics lectures from the critical period that he “was unwilling to break away fully from traditional ontology” (Ameriks 1992: 272). Gualtiero Lorini argues that a decisive break with the tradition of ontology is essential to Kant’s critical reform of metaphysics, as is reflected in his shift from “ontology” to “transcendental philosophy,” two notions that Lorini takes to be related by mere “analogy” (Lorini 2015). I agree with Lorini that a thorough reform of ontology is a pivotal part of Kant’s critical plan for metaphysics and that ontology somehow “survives within the critical philosophy” (Lorini 2015: 76). To make this case, however, I deem it important to identify “ontology” and “transcendental philosophy” in the sense of extensional equivalence. While we can detect this identification in Kant’s writings, only from his metaphysics lectures can we get a full sense of its historical and philosophical significance. In this chapter I focus on how it represents a definitive turn from as well as notable continuity with traditional treatments of ontology, particularly the Wolffian one

    A Guide to Ground in Kant's Lectures on Metaphysics

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    While scholars have extensively discussed Kant’s treatment of the Principle of Sufficient Ground in the Antinomies chapter of the Critique of Pure Reason, and, more recently, his relation to German rationalist debates about it, relatively little has been said about the exact notion of ground that figures in the PSG. My aim in this chapter is to explain Kant’s discussion of ground in the lectures and to relate it, where appropriate, to his published discussions of ground

    What Sets the Initial Rotation Rates of Massive Stars?

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    The physical mechanisms that set the initial rotation rates in massive stars are a crucial unknown in current star formation theory. Observations of young, massive stars provide evidence that they form in a similar fashion to their low-mass counterparts. The magnetic coupling between a star and its accretion disk may be sufficient to spin down low-mass pre-main sequence (PMS) stars to well below breakup at the end stage of their formation when the accretion rate is low. However, we show that these magnetic torques are insufficient to spin down massive PMS stars due to their short formation times and high accretion rates. We develop a model for the angular momentum evolution of stars over a wide range in mass, considering both magnetic and gravitational torques. We find that magnetic torques are unable to spin down either low or high mass stars during the main accretion phase, and that massive stars cannot be spun down significantly by magnetic torques during the end stage of their formation either. Spin-down occurs only if massive stars' disk lifetimes are substantially longer or their magnetic fields are much stronger than current observations suggest.Comment: 12 pages, 10 figures, Accepted for publication in Ap

    Quantifying morbidities by Adjusted Clinical Group system for a Taiwan population: A nationwide analysis

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    <p>Abstract</p> <p>Background</p> <p>The Adjusted Clinical Group (ACG) system has been used in measuring an individual's and a population's morbidities. Although all required inputs for running the ACG system are readily available, patients' morbidities and their associations to health care utilizations have been rarely studied in Taiwan. Therefore, the objective of this study was using the ACG system to quantify morbidities for Taiwanese population and to examine their relationship to ambulatory utilizations and costs.</p> <p>Methods</p> <p>This secondary analysis examined claims data for ambulatory services provided to 2.71 million representative Taiwanese in 2002 and 2003. People were grouped by the ACG system according to age, gender, and all ambulatory diagnosis codes in a given year. The software collapses the full set of ACGs into six morbidity categories (Non-users, Healthy, Low-morbidity, Moderate-, High- and Very-high) termed Resource Utilization Bands (RUBs). Each ACG was assigned a relative weight (RW), which was calculated as the ratio of mean ambulatory cost for each ACG to that for the overall. The distribution of morbidities was compared between years 2002 and 2003. The consistency of the distributions of visits, costs, and RWs of each ACG were examined for a two-year period. The relationship between people's morbidities and their ambulatory utilizations and costs was assessed.</p> <p>Results</p> <p>Ninety-eight percent of the subjects were correctly assigned to ACGs. Except for non-users (7.9 ~ 8.3%), most subjects were assigned to ACGs of acute and minor diseases and ACGs of moderate-to-high-morbid chronic diseases. The distributions of ACG-based morbidities were highly consistent (r = 0.949, <it>p < 0.001</it>) between 2002 and 2003. The ACG-specific visits (r = 0.955, <it>p < 0.001</it>), costs (r = 0.966, <it>p < 0.001</it>) and RWs (r = 0.991, <it>p < 0.001</it>) were correlated across two years. People grouped to the high-morbid ACGs had more visits and costs than those grouped to the low-morbid ACGs. Forty-six percent of the total ambulatory costs were spent by eighteen percent of the population, who were grouped to the High- and Very-high-morbidity RUBs.</p> <p>Conclusion</p> <p>This study demonstrated the feasibility, validity, and reliability of using the ACG system to measure morbidities in a Taiwan population and to explain their associations with ambulatory utilizations and costs for the whole country.</p

    CARD15 genotype and phenotype analysis in 55 pediatric patients with Crohn disease from Saxony, Germany

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    Objectives: Crohn disease is a chronic inflammatory bowel disorder that is caused by environmental and genetic factors. Mutations in the CARD15 gene have been recently identified to be associated with the disease. Until now no genetic study has focused directly on a pediatric population. Methods: The authors sequenced all 12 exons of the CARD15 gene in 55 pediatric patients with Crohn disease from Saxony. Their average age at onset was 11.2 years (1-17.5 years). The authors also evaluated the genotype-phenotype relationship in the patients. Results: Fourteen different polymorphic and/or disease-related nucleotide alterations have been identified in the patients. Sixty-five percent of their genomic DNA samples harbored at least one of six mutations within the CARD15 gene, which previously has been identified as being associated with Crohn disease. The authors found that the cytosine insertion mutation 3020insC was significantly more common in their pediatric population than in patients with Crohn disease (26% versus 11 % of the alleles) whose results were reported in the literature. The genotype-phenotype analysis showed that the authors' patients with at least one of the six CARD15 disease-associated mutations had a high risk of inflammation located in the terminal ileum and ascending colon. In 10 of 19 patients with two mutations, intestinal resection surgery was necessary because of stricturing. Conclusions: In the authors' pediatric patients, the genetic influence on Crohn disease was more pronounced than that reported in any other study, and it strongly affected the clinical phenotype. (C) 2003 Lippincott Williams Wilkins, Inc

    Intratumoral Heterogeneity in a Trp53-Null Mouse Model of Human Breast Cancer

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    Intratumoral heterogeneity correlates with clinical outcome and reflects the cellular complexity and dynamics within a tumor. Such heterogeneity is thought to contribute to radio- and chemoresistance since many treatments may only target certain tumor cell subpopulations. A better understanding of the functional interactions between various subpopulations of cells, therefore, may help in the development of effective cancer treatments. We identified a unique subpopulation of tumor cells expressing mesenchymal-like markers in a p53 null mouse model of basal-like breast cancer using fluorescence-activated cell sorting and microarray analysis. Both in vitro and in vivo experiments revealed the existence of crosstalk between these “mesenchymal-like” cells and tumor-initiating cells. Knockdown of genes encoding ligands upregulated in the mesenchymal cells and their corresponding receptors in the tumor-initiating cells resulted in reduced tumorigenicity and increased tumor latency. These studies illustrate the non-cell autonomous properties and importance of cooperativity between tumor subpopulations

    Real-time, in situ measurements of atmospheric optical absorption in the visible via photoacoustic spectroscopy--IV. Visibility degradation and aerosol optical properties in Los Angeles

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    Aerosol light absorption (babs) has been measured in real-time in Los Angeles with a validated photoacoustic technique, and its impact on visibility degradation has been examined. These measurements were collected during ten days in the summer of 1987 for the Southern California Air Quality Study (SCAQS). Aerosol babs ([lambda] = 514.5 nm) varied from an hourly average value of 7 x 10-6 m-1 in the 3-4 and 4-5 a.m. periods of 13 July to 9 x 10-5 m-1 in the 7-8 a.m. period of both 28 August and 3 September. This babs, which is due solely to elemental carbon (EC) showed a distinct diurnal pattern with low values at night, increasing around sunrise to higher values through mid-afternoon. Comparison of these data with aerosol light scattering data clearly illustrates that the contribution of aerosol light absorption to visibility degradation increases in importance under less polluted conditions. Other urban and rural studies show similar results.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/28906/1/0000743.pd

    Microservice Transition and its Granularity Problem: A Systematic Mapping Study

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    Microservices have gained wide recognition and acceptance in software industries as an emerging architectural style for autonomic, scalable, and more reliable computing. The transition to microservices has been highly motivated by the need for better alignment of technical design decisions with improving value potentials of architectures. Despite microservices' popularity, research still lacks disciplined understanding of transition and consensus on the principles and activities underlying "micro-ing" architectures. In this paper, we report on a systematic mapping study that consolidates various views, approaches and activities that commonly assist in the transition to microservices. The study aims to provide a better understanding of the transition; it also contributes a working definition of the transition and technical activities underlying it. We term the transition and technical activities leading to microservice architectures as microservitization. We then shed light on a fundamental problem of microservitization: microservice granularity and reasoning about its adaptation as first-class entities. This study reviews state-of-the-art and -practice related to reasoning about microservice granularity; it reviews modelling approaches, aspects considered, guidelines and processes used to reason about microservice granularity. This study identifies opportunities for future research and development related to reasoning about microservice granularity.Comment: 36 pages including references, 6 figures, and 3 table

    Novel STAT1 Alleles in Otherwise Healthy Patients with Mycobacterial Disease

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    The transcription factor signal transducer and activator of transcription-1 (STAT1) plays a key role in immunity against mycobacterial and viral infections. Here, we characterize three human STAT1 germline alleles from otherwise healthy patients with mycobacterial disease. The previously reported L706S, like the novel Q463H and E320Q alleles, are intrinsically deleterious for both interferon gamma (IFNG)–induced gamma-activating factor–mediated immunity and interferon alpha (IFNA)–induced interferon-stimulated genes factor 3–mediated immunity, as shown in STAT1-deficient cells transfected with the corresponding alleles. Their phenotypic effects are however mediated by different molecular mechanisms, L706S affecting STAT1 phosphorylation and Q463H and E320Q affecting STAT1 DNA-binding activity. Heterozygous patients display specifically impaired IFNG-induced gamma-activating factor–mediated immunity, resulting in susceptibility to mycobacteria. Indeed, IFNA-induced interferon-stimulated genes factor 3–mediated immunity is not affected, and these patients are not particularly susceptible to viral disease, unlike patients homozygous for other, equally deleterious STAT1 mutations recessive for both phenotypes. The three STAT1 alleles are therefore dominant for IFNG-mediated antimycobacterial immunity but recessive for IFNA-mediated antiviral immunity at the cellular and clinical levels. These STAT1 alleles define two forms of dominant STAT1 deficiency, depending on whether the mutations impair STAT1 phosphorylation or DNA binding

    P67-phox (NCF2) Lacking Exons 11 and 12 Is Functionally Active and Leads to an Extremely Late Diagnosis of Chronic Granulomatous Disease (CGD)

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    Two brothers in their fifties presented with a medical history of suspected fungal allergy, allergic bronchopulmonary aspergillosis, alveolitis, and invasive aspergillosis and pulmonary fistula, respectively. Eventually, after a delay of 50 years, chronic granulomatous disease (CGD) was diagnosed in the index patient. We found a new splice mutation in the NCF2 (p67-phox) gene, c.1000+2T→G, that led to several splice products one of which lacked exons 11 and 12. This deletion was in frame and allowed for remarkable residual NADPH oxidase activity as determined by transduction experiments using a retroviral vector. We conclude that p67-phox which lacks the 34 amino acids encoded by the two exons can still exert considerable functional activity. This activity can partially explain the long-term survival of the patients without adequate diagnosis and treatment, but could not prevent progressing lung damage
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