9,367 research outputs found
Avatars of Eurocentrism in the critique of the liberal peace
Recent scholarly critiques of the so-called liberal peace raise important political and ethical challenges to practices of postwar intervention in the global South. However, their conceptual and analytic approaches have tended to reproduce rather than challenge the intellectual Eurocentrism underpinning the liberal peace. Eurocentric features of the critiques include the methodological bypassing of target subjects in research, the analytic bypassing of subjects through frameworks of governmentality, the assumed ontological split between the ‘liberal’ and the ‘local’, and a nostalgia for the liberal subject and the liberal social contract as alternative bases for politics. These collectively produce a ‘paradox of liberalism’ that sees the liberal peace as oppressive but also the only true source of emancipation. However, the article suggests that a repoliticization of colonial difference offers an alternative ‘decolonizing’ approach to critical analysis through repositioning the analytic gaze. Three alternative research strategies for critical analysis are briefly developed
Modulation of Global Low-Frequency Motions Underlies Allosteric Regulation: Demonstration in CRP/FNR Family Transcription Factors
Allostery is a fundamental process by which ligand binding to a protein alters its activity at a distinct site. There is growing evidence that allosteric cooperativity can be communicated by modulation of protein dynamics without conformational change. The mechanisms, however, for communicating dynamic fluctuations between sites are debated. We provide a foundational theory for how allostery can occur as a function of low-frequency dynamics without a change in structure. We have generated coarse-grained models that describe the protein backbone motions of the CRP/FNR family transcription factors, CAP of Escherichia coli and GlxR of Corynebacterium glutamicum. The latter we demonstrate as a new exemplar for allostery without conformation change. We observe that binding the first molecule of cAMP ligand is correlated with modulation of the global normal modes and negative cooperativity for binding the second cAMP ligand without a change in mean structure. The theory makes key experimental predictions that are tested through an analysis of variant proteins by structural biology and isothermal calorimetry. Quantifying allostery as a free energy landscape revealed a protein ‘‘design space’’ that identified the inter- and intramolecular regulatory parameters that frame CRP/FNR family allostery. Furthermore, through analyzing CAP variants from diverse species, we demonstrate an evolutionary selection pressure to conserve residues crucial for allosteric control. This finding provides a link between the position of CRP/FNR transcription factors within the allosteric free energy landscapes and evolutionary selection pressures. Our study therefore reveals significant features of the mechanistic basis for allostery. Changes in low-frequency dynamics correlate with allosteric effects on ligand binding without the requirement for a defined spatial pathway. In addition to evolving suitable three-dimensional structures, CRP/FNR family transcription factors have been selected to occupy a dynamic space that fine-tunes biological activity and thus establishes the means to engineer allosteric mechanisms driven by low-frequency dynamics
Predictors of 25(OH)D half-life and plasma 25(OH)D concentration in The Gambia and the UK
Summary: Predictors of 25(OH)D3 half-life were factors associated with vitamin D metabolism, but were different between people in The Gambia and the UK. Country was the strongest predictor of plasma 25(OH)D concentration, probably as a marker of UVB exposure. 25(OH)D3 half-life may be applied as a tool to investigate vitamin D expenditure. Introduction: The aim of this study was to investigate predictors of 25(OH)D3 half-life and plasma 25(OH)D concentration. Methods: Plasma half-life of an oral tracer dose of deuterated-25(OH)D3 was measured in healthy men aged 24–39 years, resident in The Gambia, West Africa (n = 18) and in the UK during the winter (n = 18), countries that differ in calcium intake and vitamin D status. Plasma and urinary markers of vitamin D, calcium, phosphate and bone metabolism, nutrient intakes and anthropometry were measured. Results: Normally distributed data are presented as mean (SD) and non-normal data as geometric mean (95 % CI). Gambian compared to UK men had higher plasma concentrations of 25(OH)D (69 (13) vs. 29 (11) nmol/L; P < 0.0001); 1,25(OH)2D (181 (165, 197) vs. 120 (109, 132) pmol/L; P < 0.01); and parathyroid hormone (PTH) (50 (42, 60) vs. 33 (27, 39); P < 0.0001). There was no difference in 25(OH)D3 half-life (14.7 (3.5) days vs. 15.6 (2.5) days) between countries (P = 0.2). In multivariate analyses, 25(OH)D, 1,25(OH)2D, vitamin D binding protein and albumin-adjusted calcium (Caalb) explained 79 % of variance in 25(OH)D3 half-life in Gambians, but no significant predictors were found in UK participants. For the countries combined, Caalb, PTH and plasma phosphate explained 39 % of half-life variability. 1,25(OH)2D, weight, PTH and country explained 81 % of variability in 25(OH)D concentration; however, country alone explained 74 %. Conclusion: Factors known to affect 25(OH)D metabolism predict 25(OH)D3 half-life, but these differed between countries. Country predicted 25(OH)D, probably as a proxy measure for UVB exposure and vitamin D supply. This study supports the use of 25(OH)D half-life to investigate vitamin D metabolism
Inspiratory muscle warm-up does not improve cycling time-trial performance
Purpose: This study examined the effects of an active cycling warm-up, with and without the addition of an inspiratory muscle warm-up (IMW), on 10-km cycling time-trial performance
Indigenous knowledges and development: a postcolonial caution
As a result of the failure of formal top-down development, there has recently been increased interest in the possibilities of drawing upon the indigenous knowledges of those in the communities involved, in an attempt to produce more effective development strategies. The concept of indigenous knowledge calls for the inclusion of local voices and priorities, and promises empowerment through ownership of the process. However, there has been little critical examination of the ways in which indigenous knowledges have been included in the development process. Drawing upon postcolonial theory, this article suggests that indigenous knowledges are often drawn into development by both theorists and development institutions in a very limited way, failing to engage with other ways of perceiving development, and thus missing the possibility of devising more challenging alternatives
P5CS expression study in a new family with ALDH18A1-associated hereditary spastic paraplegia SPG9
In 2015\u20132016, we and others reported ALDH18A1 mutations causing dominant (SPG9A) or recessive (SPG9B) spastic paraplegia. In vitro production of the ALDH18A1 product, \u3941-pyrroline-5-carboxylate synthetase (P5CS), appeared necessary for cracking SPG9 disease-causing mechanisms. We now describe a baculovirus\u2013insect cell system that yields mgs of pure human P5CS and that has proven highly valuable with two novel P5CS mutations reported here in new SPG9B patients. We conclude that both mutations are disease-causing, that SPG9B associates with partial P5CS deficiency and that it is clinically more severe than SPG9A, as reflected in onset age, disability, cognitive status, growth, and dysmorphic traits
Strained graphene structures: from valleytronics to pressure sensing
Due to its strong bonds graphene can stretch up to 25% of its original size
without breaking. Furthermore, mechanical deformations lead to the generation
of pseudo-magnetic fields (PMF) that can exceed 300 T. The generated PMF has
opposite direction for electrons originating from different valleys. We show
that valley-polarized currents can be generated by local straining of
multi-terminal graphene devices. The pseudo-magnetic field created by a
Gaussian-like deformation allows electrons from only one valley to transmit and
a current of electrons from a single valley is generated at the opposite side
of the locally strained region. Furthermore, applying a pressure difference
between the two sides of a graphene membrane causes it to bend/bulge resulting
in a resistance change. We find that the resistance changes linearly with
pressure for bubbles of small radius while the response becomes non-linear for
bubbles that stretch almost to the edges of the sample. This is explained as
due to the strong interference of propagating electronic modes inside the
bubble. Our calculations show that high gauge factors can be obtained in this
way which makes graphene a good candidate for pressure sensing.Comment: to appear in proceedings of the NATO Advanced Research Worksho
Physical Activity Characteristics across GOLD Quadrants Depend on the Questionnaire Used
BACKGROUND:The GOLD multidimensional classification of COPD severity combines the exacerbation risk with the symptom experience, for which 3 different questionnaires are permitted. This study investigated differences in physical activity (PA) in the different GOLD quadrants and patient's distribution in relation to the questionnaire used. METHODS:136 COPD patients (58±21% FEV1 predicted, 34F/102M) completed COPD assessment test (CAT), clinical COPD questionnaire (CCQ) and modified Medical Research Council (mMRC) questionnaire. Exacerbation history, spirometry and 6MWD were collected. PA was objectively measured for 2 periods of 1 week, 6 months apart, in 5 European centres; to minimise seasonal and clinical variation the average of these two periods was used for analysis. RESULTS:GOLD quadrants C+D had reduced PA compared with A+B (3824 [2976] vs. 5508 [4671] steps.d-1, p<0.0001). The choice of questionnaire yielded different patient distributions (agreement mMRC-CAT κ = 0.57; CCQ-mMRC κ = 0.71; CCQ-CAT κ = 0.72) with different clinical characteristics. PA was notably lower in patients with an mMRC score ≥2 (3430 [2537] vs. 5443 [3776] steps.d-1, p <0.001) in both the low and high risk quadrants. CONCLUSIONS:Using different questionnaires changes the patient distribution and results in different clinical characteristics. Therefore, standardization of the questionnaire used for classification is critical to allow comparison of different studies using this as an entry criterion. CLINICAL TRIAL REGISTRATION:ClinicalTrials.gov NCT01388218
Learning Interpretable Rules for Multi-label Classification
Multi-label classification (MLC) is a supervised learning problem in which,
contrary to standard multiclass classification, an instance can be associated
with several class labels simultaneously. In this chapter, we advocate a
rule-based approach to multi-label classification. Rule learning algorithms are
often employed when one is not only interested in accurate predictions, but
also requires an interpretable theory that can be understood, analyzed, and
qualitatively evaluated by domain experts. Ideally, by revealing patterns and
regularities contained in the data, a rule-based theory yields new insights in
the application domain. Recently, several authors have started to investigate
how rule-based models can be used for modeling multi-label data. Discussing
this task in detail, we highlight some of the problems that make rule learning
considerably more challenging for MLC than for conventional classification.
While mainly focusing on our own previous work, we also provide a short
overview of related work in this area.Comment: Preprint version. To appear in: Explainable and Interpretable Models
in Computer Vision and Machine Learning. The Springer Series on Challenges in
Machine Learning. Springer (2018). See
http://www.ke.tu-darmstadt.de/bibtex/publications/show/3077 for further
informatio
Effects of growth rate, size, and light availability on tree survival across life stages: a demographic analysis accounting for missing values and small sample sizes.
The data set supporting the results of this article is available in the Dryad repository, http://dx.doi.org/10.5061/dryad.6f4qs. Moustakas, A. and Evans, M. R. (2015) Effects of
growth rate, size, and light availability on tree survival across life stages: a demographic analysis accounting for missing values.Plant survival is a key factor in forest dynamics and survival probabilities often vary across life stages. Studies specifically aimed at assessing tree survival are unusual and so data initially designed for other purposes often need to be used; such data are more likely to contain errors than data collected for this specific purpose
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