The Enduring State: An analysis of governance making in three mining conflicts

This is the author accepted manuscript. The final version is available from SAGE Publications via the DOI in this record.This article investigates the profound ambiguity of the state in the organization of contemporary business-society relations. On the one hand, there has been a decisive shift from government to governance, encouraging private actors, such as corporations, communities and NGOs, to address social and environmental concerns themselves, i.e. without the state’s involvement. On the other hand, however, the continued importance and relevance of the organized state is difficult to ignore. In this article we examine the role of the state in three cases of mining conflicts in Chile, one of the most important mining countries in the world. Through longitudinal, qualitative research of conflictive mining governance relations between state organizations, large corporations and local communities, we show that the modes of influence conducted by the Chilean state oscillate between direct, central steering (‘cathedral’) and indirect, dispersed vouching (‘bazaar’). Elaborating on Foucault’s concept of governmentality, we offer a hybrid theory of state organization, where the dematerialization of the state’s responsibility is seen not as the norm but rather as a particular mode of governance that sits alongside the underestimated, yet enduring, material involvement of the state

Towards a pluralist labor geography: Constrained grassroots agency and the socio-spatial fix in Dȇrsim, Turkey

This is the author accepted manuscript. The final version is available from SAGE Publications via the DOI in this record.This paper explores the interplay between capital, socio-spatial structure and grassroots agency in the context of the recent trajectories of labor geography. Based on field research conducted in Dȇrsim, Turkey, our analysis unfolds the constraining role of socio-spatial structure in the agency and praxis of grassroots movements and their geography-making and crisis-displacement from below. Through the case study, we propound a concept of socio-spatial fix to explain how this praxis conjoins with and assists capital in both staving off its recurrent crises and reproducing its own logic of accumulation. Our analysis reveals that the socio-spatial fix in Dȇrsim, which is constituted by the grassroots struggle against hydroelectric power plant projects, performs three functions. First, it facilitates the production of capitalist social relations and spaces; second, it strengthens and maintains the existing social order through temporally moderating the province’s chronic problems; and third, it provides legitimacy for the capitalist exploitation of nature, culture and histories. Our research contributes to the emerging pluralist school of labor geography, providing an empirically substantiated insight into how capital reproduces itself via socio-spatial fixes produced by constrained grassroots agency.University of Exeter Business Schoo

Non-universal minimal Z' models: present bounds and early LHC reach

We consider non-universal 'minimal' Z' models, whose additional U(1) charge is a non-anomalous linear combination of the weak hypercharge Y, the baryon number B and the partial lepton numbers (L_e, L_mu, L_tau), with no exotic fermions beyond three standard families with right-handed neutrinos. We show that the observed pattern of neutrino masses and mixing can be fully reproduced by a gauge-invariant renormalizable Lagrangian, and flavor-changing neutral currents in the charged lepton sector are suppressed by a GIM mechanism. We then discuss the phenomenology of some benchmark models. The electrophilic B-3L_e model is significantly constrained by electroweak precision tests, but still allows to fit the hint of an excess observed by CDF in dielectrons but not in dimuons. The muonphilic B-3L_mu model is very mildly constrained by electroweak precision tests, so that even the very early phase of the LHC can explore significant areas of parameter space. We also discuss the hadrophobic L_mu-L_tau model, which has recently attracted interest in connection with some puzzling features of cosmic ray spectra.Comment: 29 pages, 13 figure

Tear fluid biomarkers in ocular and systemic disease: potential use for predictive, preventive and personalised medicine

In the field of predictive, preventive and personalised medicine, researchers are keen to identify novel and reliable ways to predict and diagnose disease, as well as to monitor patient response to therapeutic agents. In the last decade alone, the sensitivity of profiling technologies has undergone huge improvements in detection sensitivity, thus allowing quantification of minute samples, for example body fluids that were previously difficult to assay. As a consequence, there has been a huge increase in tear fluid investigation, predominantly in the field of ocular surface disease. As tears are a more accessible and less complex body fluid (than serum or plasma) and sampling is much less invasive, research is starting to focus on how disease processes affect the proteomic, lipidomic and metabolomic composition of the tear film. By determining compositional changes to tear profiles, crucial pathways in disease progression may be identified, allowing for more predictive and personalised therapy of the individual. This article will provide an overview of the various putative tear fluid biomarkers that have been identified to date, ranging from ocular surface disease and retinopathies to cancer and multiple sclerosis. Putative tear fluid biomarkers of ocular disorders, as well as the more recent field of systemic disease biomarkers, will be shown

Identification of Type 1 Diabetes-Associated DNA Methylation Variable Positions That Precede Disease Diagnosis

Monozygotic (MZ) twin pair discordance for childhood-onset Type 1 Diabetes (T1D) is similar to 50%, implicating roles for genetic and non-genetic factors in the aetiology of this complex autoimmune disease. Although significant progress has been made in elucidating the genetics of T1D in recent years, the non-genetic component has remained poorly defined. We hypothesized that epigenetic variation could underlie some of the non-genetic component of T1D aetiology and, thus, performed an epigenome-wide association study (EWAS) for this disease. We generated genome-wide DNA methylation profiles of purified CD14(+) monocytes (an immune effector cell type relevant to T1D pathogenesis) from 15 T1D-discordant MZ twin pairs. This identified 132 different CpG sites at which the direction of the intra-MZ pair DNA methylation difference significantly correlated with the diabetic state, i.e. T1D-associated methylation variable positions (T1D-MVPs). We confirmed these T1D-MVPs display statistically significant intra-MZ pair DNA methylation differences in the expected direction in an independent set of T1D-discordant MZ pairs (P = 0.035). Then, to establish the temporal origins of the T1D-MVPs, we generated two further genome-wide datasets and established that, when compared with controls, T1D-MVPs are enriched in singletons both before (P = 0.001) and at (P = 0.015) disease diagnosis, and also in singletons positive for diabetes-associated autoantibodies but disease-free even after 12 years follow-up (P = 0.0023). Combined, these results suggest that T1D-MVPs arise very early in the etiological process that leads to overt T1D. Our EWAS of T1D represents an important contribution toward understanding the etiological role of epigenetic variation in type 1 diabetes, and it is also the first systematic analysis of the temporal origins of disease-associated epigenetic variation for any human complex disease

Comparison of (semi-)automatic and manually adjusted measurements of left ventricular function in dual source computed tomography using three different software tools

To assess the accuracy of (semi-)automatic measurements of left ventricular (LV) functional parameters in cardiac dual-source computed tomography (DSCT) compared to manually adjusted measurements in three different workstations. Forty patients, who underwent cardiac DSCT, were included (31 men, mean age 58 ± 14 years). Multiphase reconstructions were made with ten series at every 10% of the RR-interval. LV function analysis was performed on three different, commercially available workstations. On all three workstations, end-systolic volume (ESV), end-diastolic volume (EDV), LV ejection fraction (LVEF) and myocardial mass (MM) were calculated as automatically as possible. With the same DSCT datasets, LV functional parameters were also calculated with as many manual adjustments as needed for accurate assessment for all three software tools. For both semi-automatic as well as manual methods, time needed for evaluation was recorded. Paired t-tests were employed to calculate differences in LV functional parameters. Repeated measurements were performed to determine intra-observer and inter-observer variability. (Semi-)automatic measurements revealed a good correlation with manually adjusted measurements for Vitrea (LVEF r = 0.93, EDV r = 0.94, ESV r = 0.98 and MM r = 0.94) and Aquarius (LVEF r = 0.96, EDV r = 0.94, ESV r = 0.98 and MM r = 0.96). Also, good correlation was obtained for Circulation, except for LVEF (LVEF r = 0.45, EDV r = 0.93, ESV r = 0.92 and MM r = 0.86). However, statistically significant differences were found between (semi-)automatically and manually adjusted measurements for LVEF (P < 0.05) and ESV (P < 0.001) in Vitrea, all LV functional parameters in Circulation (P < 0.001) and EDV, ESV and MM (<0.001) in Aquarius Workstation. (Semi-)automatic measurement of LV functional parameters is feasible, but significant differences were found for at least two different functional parameters in all three workstations. Therefore, expert manual correction is recommended at all times

First observations of separated atmospheric nu_mu and bar{nu-mu} events in the MINOS detector

The complete 5.4 kton MINOS far detector has been taking data since the beginning of August 2003 at a depth of 2070 meters water-equivalent in the Soudan mine, Minnesota. This paper presents the first MINOS observations of nuµ and [overline nu ]µ charged-current atmospheric neutrino interactions based on an exposure of 418 days. The ratio of upward- to downward-going events in the data is compared to the Monte Carlo expectation in the absence of neutrino oscillations, giving Rup/downdata/Rup/downMC=0.62-0.14+0.19(stat.)±0.02(sys.). An extended maximum likelihood analysis of the observed L/E distributions excludes the null hypothesis of no neutrino oscillations at the 98% confidence level. Using the curvature of the observed muons in the 1.3 T MINOS magnetic field nuµ and [overline nu ]µ interactions are separated. The ratio of [overline nu ]µ to nuµ events in the data is compared to the Monte Carlo expectation assuming neutrinos and antineutrinos oscillate in the same manner, giving R[overline nu ][sub mu]/nu[sub mu]data/R[overline nu ][sub mu]/nu[sub mu]MC=0.96-0.27+0.38(stat.)±0.15(sys.), where the errors are the statistical and systematic uncertainties. Although the statistics are limited, this is the first direct observation of atmospheric neutrino interactions separately for nuµ and [overline nu ]µ

Sensitization of spinal cord nociceptive neurons with a conjugate of substance P and cholera toxin

<p>Abstract</p> <p>Background</p> <p>Several investigators have coupled toxins to neuropeptides for the purpose of lesioning specific neurons in the central nervous system. By producing deficits in function these toxin conjugates have yielded valuable information about the role of these cells. In an effort to specifically stimulate cells rather than kill them we have conjugated the neuropeptide substance P to the catalytic subunit of cholera toxin (SP-CTA). This conjugate should be taken up selectively by neurokinin receptor expressing neurons resulting in enhanced adenylate cyclase activity and neuronal firing.</p> <p>Results</p> <p>The conjugate SP-CTA stimulates adenylate cyclase in cultured cells that are transfected with either the NK1 or NK2 receptor, but not the NK3 receptor. We further demonstrate that intrathecal injection of SP-CTA in rats induces the phosphorylation of the transcription factor cyclic AMP response element binding protein (CREB) and also enhances the expression of the immediate early gene c-Fos. Behaviorally, low doses of SP-CTA (1 μg) injected intrathecally produce thermal hyperalgesia. At higher doses (10 μg) peripheral sensitivity is suppressed suggesting that descending inhibitory pathways may be activated by the SP-CTA induced sensitization of spinal cord neurons.</p> <p>Conclusion</p> <p>The finding that stimulation of adenylate cyclase in neurokinin receptor expressing neurons in the spinal cord produces thermal hyperalgesia is consistent with the known actions of these neurons. These data demonstrate that cholera toxin can be targeted to specific cell types by coupling the catalytic subunit to a peptide agonist for a g-protein coupled receptor. Furthermore, these results demonstrate that SP-CTA can be used as a tool to study sensitization of central neurons in vivo in the absence of an injury.</p

Impaired Chromatin Remodelling at STAT1-Regulated Promoters Leads to Global Unresponsiveness of Toxoplasma gondii-Infected Macrophages to IFN-γ

Intracellular pathogens including the apicomplexan and opportunistic parasite Toxoplasma gondii profoundly modify their host cells in order to establish infection. We have shown previously that intracellular T. gondii inhibit up-regulation of regulatory and effector functions in murine macrophages (MΦ) stimulated with interferon (IFN)-γ, which is the cytokine crucial for controlling the parasites' replication. Using genome-wide transcriptome analysis we show herein that infection with T. gondii leads to global unresponsiveness of murine macrophages to IFN-γ. More than 61% and 89% of the transcripts, which were induced or repressed by IFN-γ in non-infected MΦ, respectively, were not altered after stimulation of T. gondii-infected cells with IFN-γ. These genes are involved in a variety of biological processes, which are mostly but not exclusively related to immune responses. Analyses of the underlying mechanisms revealed that IFN-γ-triggered nuclear translocation of STAT1 still occurred in Toxoplasma-infected MΦ. However, STAT1 bound aberrantly to oligonucleotides containing the IFN-γ-responsive gamma-activated site (GAS) consensus sequence. Conversely, IFN-γ did not induce formation of active GAS-STAT1 complexes in nuclear extracts from infected MΦ. Mass spectrometry of protein complexes bound to GAS oligonucleotides showed that T. gondii-infected MΦ are unable to recruit non-muscle actin to IFN-γ-responsive DNA sequences, which appeared to be independent of stimulation with IFN-γ and of STAT1 binding. IFN-γ-induced recruitment of BRG-1 and acetylation of core histones at the IFN-γ-regulated CIITA promoter IV, but not β-actin was diminished by >90% in Toxoplasma-infected MΦ as compared to non-infected control cells. Remarkably, treatment with histone deacetylase inhibitors restored the ability of infected macrophages to express the IFN-γ regulated genes H2-A/E and CIITA. Taken together, these results indicate that Toxoplasma-infected MΦ are unable to respond to IFN-γ due to disturbed chromatin remodelling, but can be rescued using histone deacetylase inhibitors