82 research outputs found

    The Refugee Camp as Warscape: Violent Cosmologies, “Rebelization,” and Humanitarian Governance in Kakuma, Kenya

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    This paper approaches Kakuma refugee camp in Kenya as a “warscape” and explores the role that multiple understandings and experiences with violence play in the everyday organization of the camp. The dynamics of war-related imageries and various forms of past, present and symbolic violence translate into power processes and forms of spatial and social ordering that are explored as processes of place making. Rather than seeing violence as something exceptional, this paper explores how over the years of its existence since 1992 the camp was shaped by the narratives, experiences and understandings of violence and rebel histories, and the associations between refugees and armed movements. <br/

    ICES coordinated acoustic survey of ICES divisions IIIa, IVa, IVb AND Via (North) 2002 Results and long term trends

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    Six surveys were carried out during late June and July covering most of the continental shelf north of 54oN in the North Sea and to the west of Scotland to a northern limit of 62oN. The eastern edge of the survey area was bounded by the Norwegian and Danish, Swedish and German coasts, and to the west by the shelf edge between 200 and 400 m depth. The surveys are reported individually in the report of the planning group for herring surveys, and a combined report has been prepared from the data from all surveys. The combined survey results provide spatial distributions of herring abundance by number and biomass at age by statistical rectangle; and distributions of mean weight and fraction mature at age. The estimates of North Sea autumn spawning herring are consistent with previous years at 2.9 million tonnes and 17,200 million herring. The survey also shows two exceptional year classes of herring (the 1998 and 2000 year classes) in the North Sea, which is consistent with the observation of exceptionally large year classes observed in the MIK and IBTS surveys. The estimates of Western Baltic spring spawning herring SSB are 255,000 tonnes and 2.9 millions (Table 2) and show a large increase compared with the previous year. The Western Baltic survey produces a rather noisy signal but the indications are of a stock that is higher now than between 1996 to 2000. The West of Scotland survey estimates of 548,000 tonnes and 2,900 million and shows the high 1995 year class again this year. The 1998 year class now (3 ring) is also a large one. Total adult mortality shows much lower mortality than last year (0.1 compared to 0.5 ) but the mean mortality over the last 4 years has been 0.3: this is consistent with the 2002 assessment that the stock is lightly exploited. The overall time series of abundance by age from 1989 to 2002 are summarised by simple models describing the spatial distribution over time. The changes over time with latitude, longitude and area occupied are compared with changes in abundance

    ICES coordinated acoustic survey of ICES divisions IIIa, IVa, IVb AND Via (North) 2002 Results and long term trends

    Get PDF
    Six surveys were carried out during late June and July covering most of the continental shelf north of 54oN in the North Sea and to the west of Scotland to a northern limit of 62oN. The eastern edge of the survey area was bounded by the Norwegian and Danish, Swedish and German coasts, and to the west by the shelf edge between 200 and 400 m depth. The surveys are reported individually in the report of the planning group for herring surveys, and a combined report has been prepared from the data from all surveys. The combined survey results provide spatial distributions of herring abundance by number and biomass at age by statistical rectangle; and distributions of mean weight and fraction mature at age. The estimates of North Sea autumn spawning herring are consistent with previous years at 2.9 million tonnes and 17,200 million herring. The survey also shows two exceptional year classes of herring (the 1998 and 2000 year classes) in the North Sea, which is consistent with the observation of exceptionally large year classes observed in the MIK and IBTS surveys. The estimates of Western Baltic spring spawning herring SSB are 255,000 tonnes and 2.9 millions (Table 2) and show a large increase compared with the previous year. The Western Baltic survey produces a rather noisy signal but the indications are of a stock that is higher now than between 1996 to 2000. The West of Scotland survey estimates of 548,000 tonnes and 2,900 million and shows the high 1995 year class again this year. The 1998 year class now (3 ring) is also a large one. Total adult mortality shows much lower mortality than last year (0.1 compared to 0.5 ) but the mean mortality over the last 4 years has been 0.3: this is consistent with the 2002 assessment that the stock is lightly exploited. The overall time series of abundance by age from 1989 to 2002 are summarised by simple models describing the spatial distribution over time. The changes over time with latitude, longitude and area occupied are compared with changes in abundance

    The effect of a high-fat diet on brain plasticity, inflammation and cognition in female ApoE4-knockin and ApoE-knockout mice

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    Apolipoprotein E4 (ApoE4), one of three common isoforms of ApoE, is a major risk factor for late-onset Alzheimer disease (AD). ApoE-deficient mice, as well as mice expressing human ApoE4, display impaired learning and memory functions and signs of neurodegeneration. Moreover, ApoE protects against high-fat (HF) diet induced neurodegeneration by its role in the maintenance of the integrity of the blood-brain barrier. The influence of a HF diet on the progression of AD-like cognitive and neuropathological changes was assessed in wild-type (WT), human ApoE4 and ApoE-knockout (ApoE-/-) mice to evaluate the modulatory role of ApoE in this process. From 12 months of age, female WT, ApoE4, and ApoE-/- mice were fed either a standard or a HF diet (19% butter, 0.5% cholate, 1.25% cholesterol) throughout life. At 15 months of age mice performed the Morris water maze, evaluating spatial learning and memory. ApoE-/- showed increased spatial learning compared to WT mice (p = 0.009). HF diet improved spatial learning in WT mice (p = 0.045), but did not affect ApoE4 and ApoE-/- mice. Immunohistochemical analyses of the hippocampus demonstrated increased neuroinflammation (CD68) in the cornu ammonis 1 (CA1) region in ApoE4 (p = 0.001) and in ApoE-/- (p = 0.032) mice on standard diet. HF diet tended to increase CD68 in the CA1 in WT mice (p = 0.052), while it decreased in ApoE4 (p = 0.009), but ApoE-/- remained unaffected. A trend towards increased neurogenesis (DCX) was found in both ApoE4 (p = 0.052) and ApoE-/- mice (p = 0.068). In conclusion, these data suggest that HF intake induces different effects in WT mice compared to ApoE4 and ApoE-/- with respect to markers for cognition and neurodegeneration. We propose that HF intake inhibits the compensatory mechanisms of neuroinflammation and neurogenesis in aged female ApoE4 and ApoE-/- mice

    De toekomst van werk. Over ecologische, technologische en politieke ontwikkelingen en het belang van strategische keuzes en politieke strijd

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    n dit artikel wordt een aantal factoren besproken die naar onze mening mondiaal van invloed zullen zijn op de toekomst van arbeid. We lichten er drie belangrijke factoren uit, namelijk ecologische, technologische en politieke invloedfactoren. Uit onze beschouwing komt een gemengd beeld over de toekomst van werk naar voren. We zien groei van vakmanschap en decent work, bijvoorbeeld gekoppeld aan de energietransitie en in de micro-elektronica, maar ook het voortduren van werk dat niet voldoet aan de (ILO-)standaarden van decent work zoals nachtwerk in distributiecentra en platformarbeid. Het voortdurende proces waarin de toekomst van arbeid zich ontwikkelt is onderhevig aan strategische keuzen en politieke strijd van verschillende stakeholders in de context van ecologie, technologie en politiek. De vorm (loonarbeid, zelfstandige arbeid) en inhoud van werk, de beroepenstructuur en de arbeidsverhoudingen veranderen door onder andere AI en overheidsbeleid. De Europese politiek kiest een actievere opstelling. Voor de Europese Commissie staat beleid gericht op regulering van bijvoorbeeld kunstmatige intelligente (artifical intelligence; AI) niet op zichzelf, maar wordt ook geleid door het streven naar bescherming van het Europese type open society met democratische vrijheden voor burgers, onafhankelijke rechtspraak en vrije media. Stakeholders die, net als wij, decent work en de open society als referentiepunt hebben voor de gewenste toekomst van werk zullen zich daarvoor in het politieke speelveld hard moeten maken

    Imidazoacridinone-dependent lysosomal photodestruction: a pharmacological Trojan horse approach to eradicate multidrug-resistant cancers

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    Multidrug resistance (MDR) remains a primary hindrance to curative cancer therapy. Thus, introduction of novel strategies to overcome MDR is of paramount therapeutic significance. Sequestration of chemotherapeutics in lysosomes is an established mechanism of drug resistance. Here, we show that MDR cells display a marked increase in lysosome number. We further demonstrate that imidazoacridinones (IAs), which are cytotoxic fluorochromes, undergo a dramatic compartmentalization in lysosomes because of their hydrophobic weak base nature. We hence developed a novel photoactivation-based pharmacological Trojan horse approach to target and eradicate MDR cancer cells based on photo-rupture of IA-loaded lysosomes and tumor cell lysis via formation of reactive oxygen species. Illumination of IA-loaded cells resulted in lysosomal photodestruction and restoration of parental cell drug sensitivity. Lysosomal photodestruction of MDR cells overexpressing the key MDR efflux transporters ABCG2, ABCB1 or ABCC1 resulted in 10- to 52-fold lower IC(50) values of various IAs, thereby restoring parental cell sensitivity. Finally, in vivo application of this photodynamic therapy strategy after i.v. injection of IAs in human ovarian tumor xenografts in the chorioallantoic membrane model revealed selective destruction of tumors and their associated vasculature. These findings identify lysosomal sequestration of IAs as an Achilles heel of MDR cells that can be harnessed to eradicate MDR tumor cells via lysosomal photodestruction

    The luminosity function of Ly-alpha emitters at 2.3 < z < 4.6 from integral-field spectroscopy

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    We have used VIsible MultiObject Spectrograph Integral-Field Unit (VIMOS-IFU) observations centred on a radio galaxy at z=2.9 to search for Ly-alpha emitters within a comoving volume of ~ 10^4 Mpc^3. We find 14 Ly-alpha emitters with flux > 1.4 x 10^-20 Wm^-2, yielding a comoving space density of 0.0018 +/- 0.0006 Mpc^-3. We fit a Schechter luminosity function which agrees well with previous studies both at similar redshift (z ~ 3.4) and higher redshift (z ~ 5.7). We therefore find no evidence for evolution in the properties of Ly-alpha emitters between 3 < z < 6, although our sample is small. By summing the star-formation rates of the individual Ly-alpha emitters we find a total cosmic star-formation rate density of rho_SFR = 6.7 +/- 0.5 x 10^-3 M_solar yr^-1 Mpc^-3. Integrating over the luminosity function for the combined Ly-alpha surveys at z ~ 3.4 and accounting for the difference in obscuration between the Ly-alpha line and the UV-continuum yields an estimate of rho_SFR ~ 2.2 x 10^-2 M_solar yr^-1 Mpc^-3, in line with previous multi-colour and narrow-band surveys of high-redshift star-forming galaxies. The detection of high-redshift emission-line galaxies in our volumetric search shows that the unique capabilities of wide-field integral-field spectroscopy are well suited in searching for high-redshift galaxies in a relatively unbiased manner.Comment: 12 pages, 6 figures, accepted for publication in MNRA

    Occupational exposure to gases/fumes and mineral dust affect DNA methylation levels of genes regulating expression

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    Many workers are daily exposed to occupational agents like gases/fumes, mineral dust or biological dust, which could induce adverse health effects. Epigenetic mechanisms, such as DNA methylation, have been suggested to play a role. We therefore aimed to identify differentially methylated regions (DMRs) upon occupational exposures in never-smokers and investigated if these DMRs associated with gene expression levels. To determine the effects of occupational exposures independent of smoking, 903 never-smokers of the LifeLines cohort study were included. We performed three genome-wide methylation analyses (Illumina 450 K), one per occupational exposure being gases/fumes, mineral dust and biological dust, using robust linear regression adjusted for appropriate confounders. DMRs were identified using comb-p in Python. Results were validated in the Rotterdam Study (233 never-smokers) and methylation-expression associations were assessed using Biobank-based Integrative Omics Study data (n = 2802). Of the total 21 significant DMRs, 14 DMRs were associated with gases/fumes and 7 with mineral dust. Three of these DMRs were associated with both exposures (RPLP1 and LINC02169 (2x)) and 11 DMRs were located within transcript start sites of gene expression regulating genes. We replicated two DMRs with gases/fumes (VTRNA2-1 and GNAS) and one with mineral dust (CCDC144NL). In addition, nine gases/fumes DMRs and six mineral dust DMRs significantly associated with gene expression levels. Our data suggest that occupational exposures may induce differential methylation of gene expression regulating genes and thereby may induce adverse health effects. Given the millions of workers that are exposed daily to occupational exposures, further studies on this epigenetic mechanism and health outcomes are warranted

    Resolving sepsis-induced immunoparalysis via trained immunity by targeting interleukin-4 to myeloid cells.

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    Immunoparalysis is a compensatory and persistent anti-inflammatory response to trauma, sepsis or another serious insult, which increases the risk of opportunistic infections, morbidity and mortality. Here, we show that in cultured primary human monocytes, interleukin-4 (IL4) inhibits acute inflammation, while simultaneously inducing a long-lasting innate immune memory named trained immunity. To take advantage of this paradoxical IL4 feature in vivo, we developed a fusion protein of apolipoprotein A1 (apoA1) and IL4, which integrates into a lipid nanoparticle. In mice and non-human primates, an intravenously injected apoA1-IL4-embedding nanoparticle targets myeloid-cell-rich haematopoietic organs, in particular, the spleen and bone marrow. We subsequently demonstrate that IL4 nanotherapy resolved immunoparalysis in mice with lipopolysaccharide-induced hyperinflammation, as well as in ex vivo human sepsis models and in experimental endotoxemia. Our findings support the translational development of nanoparticle formulations of apoA1-IL4 for the treatment of patients with sepsis at risk of immunoparalysis-induced complications.We thank M. Jaeger (Radboudumc) for kindly providing flourescein isothiocyanate-labelled Candida albicans. D. Williams (East Tennessee State University) provided the β-glucan we used in our initial experiments. H. Lemmers (Radboudumc) kindly prepared the purified lipopolysaccharide used for stimulation of primary human monocytes and macrophages. Part of the figures were prepared using (among other software) Biorender.com. B.N. is supported by a National Health and Medical Research Council (Australia) Investigator Grant (APP1173314). This work was supported by National Institutes of Health grants R01 HL144072, R01 CA220234 and P01 HL131478, as well as a Vici grant from the Dutch Research Council NWO and an ERC Advanced Grant (all to W.J.M.M.). M.G.N. was supported by a Spinoza grant from Dutch Research Council NWO and an ERC Advanced Grant (#833247).S

    Validation, comparison, and combination of algorithms for automatic detection of pulmonary nodules in computed tomography images: The LUNA16 challenge

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    Automatic detection of pulmonary nodules in thoracic computed tomography (CT) scans has been an active area of research for the last two decades. However, there have only been few studies that provide a comparative performance evaluation of different systems on a common database. We have therefore set up the LUNA16 challenge, an objective evaluation framework for automatic nodule detection algorithms using the largest publicly available reference database of chest CT scans, the LIDC-IDRI data set. In LUNA16, participants develop their algorithm and upload their predictions on 888 CT scans in one of the two tracks: 1) the complete nodule detection track where a complete CAD system should be developed, or 2) the false positive reduction track where a provided set of nodule candidates should be classified. This paper describes the setup of LUNA16 and presents the results of the challenge so far. Moreover, the impact of combining individual systems on the detection performance was also investigated. It was observed that the leading solutions employed convolutional networks and used the provided set of nodule candidates. The combination of these solutions achieved an excellent sensitivity of over 95% at fewer than 1.0 false positives per scan. This highlights the potential of combining algorithms to improve the detection performance. Our observer study with four expert readers has shown that the best system detects nodules that were missed by expert readers who originally annotated the LIDC-IDRI data. We released this set of additional nodules for further development of CAD systems
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