495 research outputs found
Disaggregating political authority: what's wrong with Rawlsian civil disobedience?
Contemporary philosophical and theoretical discussions of civil disobedience hope to contribute to significant political debates around when and in which forms political dissent, protest and resistance is appropriate. In doing so, they often focus on and criticize John Rawls' work on civil disobedience. However, ignoring the frame in which Rawls discusses civil disobedience has led critics to wrongly attack his theory for being too restrictive when it is more likely to be too permissive. That permissiveness depends on treating any political order which does not come close to fulfilling his theory of justice as absolutely illegitimate. In this sense, Rawls’ theory of political authority is binary and demanding. The problems his theory shares with most others, including his critics’, show that political authority needs to be disaggregated to make sense of the conditions under which different forms of protest and resistance are appropriate
Can Modus Vivendi Save Liberalism from Moralism? A Critical Assessment of John Gray’s Political Realism
This chapter assesses John Gray’s modus vivendi-based justification for liberalism. I argue that his approach is preferable to the more orthodox deontological or teleological justificatory strategies, at least because of the way it can deal with the problem of diversity. But then I show how that is not good news for liberalism, for grounding liberal political authority in a modus vivendi undermines liberalism’s aspiration to occupy a privileged normative position vis-à -vis other kinds of regimes. So modus vivendi can save liberalism from moralism, but at cost many liberals will not be prepared to pay
The Impact of Exploring Computer Science in Wisconsin: Where Disadvantage is an Advantage
Assessing the impact of regional or statewide interventions in primary and secondary school (K-12) computer science (CS) education is difficult for a variety of reasons. Qualitative survey data provide only a limited view of impacts, but quantitative data can be notoriously difficult to acquire at scale from large numbers of classrooms, schools, or local educational authorities. In this paper, we use several publicly available data sources to glean insights into public high school CS enrollments across an entire U.S. state. Course enrollments with NCES course codes and local descriptors, school-level demographic data, and school geographic attendance boundaries can be combined to highlight where CS offerings persist and thrive, how CS enrollments change over time, and the ultimate quantitative impact of a statewide intervention. We propose a more appropriate level of data aggregation for these types of quantitative studies than has been undertaken in previous work while demonstrating the importance of a contextual aggregation process. The results of our disparate impact analysis for the first time quantify the impact of a statewide Exploring Computer Science (ECS) program rollout on economic groups across the region. Our blueprint for this analysis can serve as a template to guide and assess large-scale K-12 CS interventions wherever detailed project evaluation methods cannot scale to encompass the entire study area, especially in cases where attribute heterogeneity is a significant issue
Hypoxia regulates FGFR3 expression via HIF-1α and miR-100 and contributes to cell survival in non-muscle invasive bladder cancer
Background: Non-muscle invasive (NMI) bladder cancer is characterised by increased expression and activating mutations of FGFR3. We have previously investigated the role of microRNAs in bladder cancer and have shown that FGFR3 is a target of miR-100. In this study, we investigated the effects of hypoxia on miR-100 and FGFR3 expression, and the link between miR-100 and FGFR3 in hypoxia.
Methods: Bladder cancer cell lines were exposed to normoxic or hypoxic conditions and examined for the expression of FGFR3
by quantitative PCR (qPCR) and western blotting, and miR-100 by qPCR. The effect of FGFR3 and miR-100 on cell viability in twodimensional (2-D) and three-dimensional (3-D) was examined by transfecting siRNA or mimic-100, respectively.
Results: In NMI bladder cancer cell lines, FGFR3 expression was induced by hypoxia in a transcriptional and HIF-1a-dependent
manner. Increased FGFR3 was also in part dependent on miR-100 levels, which decreased in hypoxia. Knockdown of FGFR3 led to a decrease in phosphorylation of the downstream kinases mitogen-activated protein kinase (MAPK) and protein kinase B (PKB), which was more pronounced under hypoxic conditions. Furthermore, transfection of mimic-100 also decreased phosphorylation of MAPK and PKB. Finally, knocking down FGFR3 profoundly decreased 2-D and 3-D cell growth, whereas introduction of mimic-100 decreased 3-D growth of cells.
Conclusion: Hypoxia, in part via suppression of miR-100, induces FGFR3 expression in bladder cancer, both of which have an
important role in maintaining cell viability under conditions of stress
Catchment-wide interactive effects of anthropogenic structures and river levels on fish spawning migrations
Worldwide, rivers are extensively fragmented by anthropogenic structures, reducing longitudinal connectivity, inhibiting migration and leading to severe declines in many fish populations, especially for diadromous species. However, few studies have determined the effects of annual differences in hydrology on catchment penetration past barriers to spawning habitats. We investigated the upstream spawning migration of 120 (n = 61 & 59) acoustic tagged river lamprey (Lampetra fluviatilis) across two contrasting (dry and wet) years in the River Yorkshire Ouse, England. Overall, significantly more lamprey reached spawning habitat (76% vs 39%) and penetrated significantly further upstream (median [km] from release, 53.9 vs 16.8) in the wet year than the dry year. Passage at weirs was almost exclusively during elevated river levels, which directly and collectively influenced catchment-wide distribution, especially in the dry year. Indeed, higher proportions entered two upper tributaries in the wet year (9.8% vs 27.1% and 9.8% vs 30.5%), due to increased passage efficiencies at the two main river weirs (60.5–87.5% and 54.5–83.8%), and reached assumed spawning locations 66.5% and 10.9% quicker. By contrast, there was no difference in numbers of lamprey entering, or time taken to arrive at assumed spawning location, in the two lower river tributaries between years. Our study supports the landscape-scale paradigm for ecosystem restoration because of the observed catchment-level effects of hydrology and barrier distribution on fish migration. Connectivity restoration for migratory fish should be implemented at a catchment scale, with planning incorporating spatial information regarding accessibility to key habitats to reap the largest gains
1,2-Dichlorohexafluoro-Cyclobutane (1,2-c-C4F6Cl2, R-316c) a Potent Ozone Depleting Substance and Greenhouse Gas: Atmospheric Loss Processes, Lifetimes, and Ozone Depletion and Global Warming Potentials for the (E) and (Z) stereoisomers
The atmospheric processing of (E)- and (Z)-1,2-dichlorohexafluorocyclobutane (1,2-c-C4F6Cl2, R-316c) was examined in this work as the ozone depleting (ODP) and global warming (GWP) potentials of this proposed replacement compound are presently unknown. The predominant atmospheric loss processes and infrared absorption spectra of the R-316c isomers were measured to provide a basis to evaluate their atmospheric lifetimes and, thus, ODPs and GWPs. UV absorption spectra were measured between 184.95 to 230 nm at temperatures between 214 and 296 K and a parametrization for use in atmospheric modeling is presented. The Cl atom quantum yield in the 193 nm photolysis of R- 316c was measured to be 1.90 +/- 0.27. Hexafluorocyclobutene (c-C4F6) was determined to be a photolysis co-product with molar yields of 0.7 and 1.0 (+/-10%) for (E)- and (Z)-R-316c, respectively. The 296 K total rate coefficient for the O(1D) + R-316c reaction, i.e., O(1D) loss, was measured to be (1.56 +/- 0.11) 10(exp 10)cu cm/ molecule/s and the reactive rate coefficient, i.e., R-316c loss, was measured to be (1.36 +/- 0.20) 10(exp 10)cu cm/molecule/s corresponding to a approx. 88% reactive yield. Rate coefficient upper-limits for the OH and O3 reaction with R-316c were determined to be <2.3 10(exp 17) and <2.0 10(exp 22)cu cm/molecule/s, respectively, at 296 K. The quoted uncertainty limits are 2(sigma) and include estimated systematic errors. Local and global annually averaged lifetimes for the (E)- and (Z)-R-316c isomers were calculated using a 2-D atmospheric model to be 74.6 +/- 3 and 114.1 +/-10 years, respectively, where the estimated uncertainties are due solely to the uncertainty in the UV absorption spectra. Stratospheric photolysis is the predominant atmospheric loss process for both isomers with the O(1D) reaction making a minor, approx. 2% for the (E) isomer and 7% for the (Z) isomer, contribution to the total atmospheric loss. Ozone depletion potentials for (E)- and (Z)-R-316c were calculated using the 2-D model to be 0.46 and 0.54, respectively. Infrared absorption spectra for (E)- and (Z)-R-316c were measured at 296 K and used to estimate their radiative efficiencies (REs) and GWPs; 100-year time-horizon GWPs of 4160 and 5400 were obtained for (E)- and (Z)-R-316c, respectively. Both isomers of R-316c are shown in this work to be long-lived ozone depleting substances and potent greenhouse gases
How to do realistic political theory (and why you might want to)
In recent years, a number of realist thinkers have charged much contemporary political theory with being idealistic and moralistic. While the basic features of the realist counter-movement are reasonably well understood, realism is still considered a critical, primarily negative creed which fails to offer a positive, alternative way of thinking normatively about politics. Aiming to counteract this general perception, in this article I draw on Bernard Williams’s claims about how to construct a politically coherent conception of liberty from the non-political value of freedom. I do this because Williams’s argument provides an illuminating example of the distinctive nature of realist political thinking and its attractions. I argue that Williams’s account of realist political thinking challenges the orthodox moralist claim that normative political arguments must be guided by an ideal ethical theory. I then spell out the repercussions Williams’s claims about the significance of political opposition and non-moralised accounts of motivation have for our understanding of the role and purpose of political theory. I conclude by defending the realist claim that action-guiding political theory should accordingly take certain features of our politics as given, most centrally the reality of political opposition and the passions and experiences that motivate them. On this reading political realism offers a viable way of thinking about political values which cannot be understood in terms of the categories of intellectual separation – ideal/nonideal or fact-insensitive/fact-sensitive – that have marked political theory in recent years
Facts, Principles, and (Real) Politics
Should our factual understanding of the world influence our normative theorising about it? G.A. Cohen has argued that our ultimate normative principles should not be constrained by facts. Many others have defended or are committed to various versions or subsets of that claim. In this paper I dispute those positions by arguing that, in order to resist the conclusion that ultimate normative principles rest on facts about possibility or conceivability, one has to embrace an unsatisfactory account of how principles generate normative political judgments. So political theorists have to choose between principles ostensibly unbiased by our current understanding of human motivation and political reality, or principles capable of reliably generating political judgments. I conclude with wider methodological observations in defence of the latter option, and so of a return to political philosophy’s traditional blend of normative and descriptive elements
Identification of serum angiopoietin-2 as a biomarker for clinical outcome of colorectal cancer patients treated with bevacizumab-containing therapy
BACKGROUND: The combination of chemotherapy with the vascular endothelial growth factor (VEGF) antibody bevacizumab is a standard of care in advanced colorectal cancer (CRC). However, biomarkers predicting outcome of bevacizumab-containing treatment are lacking. As angiopoietin-2 (Ang-2) is a key regulator of vascular remodelling in concert with VEGF, we investigated its role as a biomarker in metastatic CRC. METHODS: Serum Ang-2 levels were measured in 33 healthy volunteers and 90 patients with CRC. Of these, 34 had metastatic disease and received bevacizumab-containing therapy. To determine the tissue of origin of Ang-2, quantitative real-time PCR was performed on microdissected cryosections of human CRC and in a murine xenograft model of CRC using species-specific amplification. RESULTS: Ang-2 originated from the stromal compartment of CRC tissues. Serum Ang-2 levels were significantly elevated in patients with metastatic CRC compared with healthy controls. Amongst patients receiving bevacizumab-containing treatment, low pre-therapeutic serum Ang-2 levels were associated with a significant better response rate (82 vs 31%; P<0.01), a prolonged median progression-free survival (14.1 vs 8.5 months; P<0.01) and a reduction of 91% in the hazard of death (P<0.05). CONCLUSION: Serum Ang-2 is a candidate biomarker for outcome of patients with metastatic CRC treated with bevacizumab-containing therapy, and it should be further validated to customise combined chemotherapeutic and anti-angiogenic treatment. British Journal of Cancer (2010) 103, 1407-1414. doi: 10.1038/sj.bjc.6605925 www.bjcancer.com Published online 5 October 2010 (C) 2010 Cancer Research U
Thermal conductivity of refractory glass fibres
In the present study, the current international
standards and corresponding apparatus for measuring the
thermal conductivity of refractory glass fibre products have
been reviewed. Refractory glass fibres are normally produced
in the form of low-density needled mats. A major
issue with thermal conductivity measurements of these
materials is lack of reproducibility in the test results due to
transformation of the test material during the test. Also
needled mats are inherently inhomogeneous, and this poses
additional problems. To be able to compare the various
methods of thermal conductivity measurement, a refractory
reference material was designed which is capable of
withstanding maximum test temperatures (1673 K) with
minimum transformation. The thermal conductivity of this
reference material was then measured using various
methods according to the different standards surveyed. In
order to compare different materials, samples have been
acquired from major refractory glass fibre manufacturers
and the results have been compared against the newly
introduced reference material. Materials manufactured by
melt spinning, melt blowing and sol–gel have been studied,
and results compared with literature values
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