516 research outputs found

    A harmony not foreseen. A study of the prevalence of conflict in NGO - local government relations in Uganda

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    The ambition of the study is to explore the area of tension between the local government and non-governmental organizations engaged in service provision in Uganda. By applying the method of most different systems design, the study aims at determining if conflict is more frequent in a high-risk environment compared to a low-risk ditto, as specified by the theory of Michael Bratton?s. Lira District has been chosen to represent the first setting on account of its high level of internal violence and militarization in combination with a significant NGO sector and weak administrative capacity. In contrast, Kabale District has been singled out on the basis of its stability and comparably smaller NGO community. Despite the favourable conditions provided, the outcome does not diverge sufficiently to render the theory explanatory power. This reality is connected to the fact that conventional theory disregards the impact of NGO behaviour on the quality of the relationship. The particular strategies selected in dealing with local government reflect the NGO's normative orientation, which needs to be taken into consideration in order to produce reliable results

    Fiction as a Means to Understanding the Dynamics of Empathy

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    The current study investigated whether the reflective reading of fiction can provide an experiential definition of empathy to supplement more traditional concept analyses. A secondary aim was to look at the rates of absorption (loss of time and space) relative to the rate of reported empathic engagement. Based on earlier studies on reading fiction as an engagement in a social simulation, it was predicted that because fiction is a controlled experience, reading and talking about fiction could provide a forum in which to examine actual experiences of empathy elicitation in relation to an evolving situation. A survey was conducted with 210 student participants over a three-year period. The results show that the empathetic response to narrative is affected in a variety of ways by the presence or absence of an initial sense of affinity and by cognitive input over time, that is, the changing perception of characters and the situations with which they are confronted. Adept readers are more likely to experience absorption, and those who experience absorption are more likely to be empathetically responsive to input and changes in a situation. Empathetic emotions and cognitive empathy can be experienced for multiple objects simultaneously in one situation and relate to past events and potential futures, but they also shift from object to object

    Alternative mechanisms of p53 action during the unfolded protein response

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    The tumor suppressor protein p53 orchestrates cellular responses to a vast number of stresses, with DNA damage and oncogenic activation being some of the best described. The capacity of p53 to control cellular events such as cell cycle progression, DNA repair, and apoptosis, to mention some, has been mostly linked to its role as a transcription factor. However, how p53 integrates different signaling cascades to promote a particular pathway remains an open question. One way to broaden its capacity to respond to different stimuli is by the expression of isoforms that can modulate the activities of the full-length protein. One of these isoforms is p47 (p53/47, Δ40p53, p53ΔN40), an alternative translation initiation variant whose expression is specifically induced by the PERK kinase during the Unfolded Protein Response (UPR) following Endoplasmic Reticulum stress. Despite the increasing knowledge on the p53 pathway, its activity when the translation machinery is globally suppressed during the UPR remains poorly understood. Here, we focus on the expression of p47 and we propose that the alternative initiation of p53 mRNA translation offers a unique condition-dependent mechanism to differentiate p53 activity to control cell homeostasis during the UPR. We also discuss how the manipulation of these processes may influence cancer cell physiology in light of therapeutic approaches

    Kinetic models for dilute solutions of dumbbells in non-homogeneous flows revisited

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    We propose a two fluid theory to model a dilute polymer solution assuming that it consists of two phases, polymer and solvent, with two distinct macroscopic velocities. The solvent phase velocity is governed by the macroscopic Navier-Stokes equations with the addition of a force term describing the interaction between the two phases. The polymer phase is described on the mesoscopic level using a dumbbell model and its macroscopic velocity is obtained through averaging. We start by writing down the full phase-space distribution function for the dumbbells and then obtain the inertialess limits for the Fokker-Planck equation and for the averaged friction force acting between the phases from a rigorous asymptotic analysis. The resulting equations are relevant to the modelling of strongly non-homogeneous flows, while the standard kinetic model is recovered in the locally homogeneous case

    Particulate blood analogues reproducing the erythrocytes cell-free layer in a microfluidic device containing a hyperbolic contraction

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    The interest in the development of blood analogues has been increasing recently as a consequence of the increment in the number of experimental hemodynamic studies and the difficulties associated with the manipulation of real blood in vitro because of ethical, economical or hazardous issues. Although one-phase Newtonian and non-Newtonian blood analogues can be found in the literature, there are very few studies related to the use of particulate solutions in which the particles mimic the behaviour of the red blood cells (RBCs) or erythrocytes. One of the most relevant effects related with the behaviour of the erythrocytes is a cell-free layer (CFL) formation, which consists in the migration of the RBCs towards the center of the vessel forming a cell depleted plasma region near the vessel walls, which is known to happen in in vitro microcirculatory environments. Recent studies have shown that the CFL enhancement is possible with an insertion of contraction and expansion region in a straight microchannel. These effects are useful for cell manipulation or sorting in lab-on-chip studies. In this experimental study we present particulate Newtonian and non-Newtonian solutions which resulted in a rheological blood analogue able to form a CFL, downstream of a microfluidic hyperbolic contraction, in a similar way of the one formed by healthy RBCs.The authors acknowledge the financial support provided by Fundação para a Ciência e a Tecnologia (FCT), COMPETE and FEDER through projects PTDC/SAU-BEB/105650/2008, PTDC/SAU-ENB/116929/2010, PTDC/EQU-FTT/118716/2010, EXPL/EMS-SIS/2215/2013, EXPL/EMS-TRA/2306/2013, fellowships SFRH/BD/89077/2012, SFRH/BPD/69663/2010 and SFRH/BPD/69664/2010 and grants IF/00148/2013 and IF/00190/2013.info:eu-repo/semantics/publishedVersio

    Bacterial genospecies that are not ecologically coherent : population genomics of Rhizobium leguminosarum

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    Biological species may remain distinct because of genetic isolation or ecological adaptation, but these two aspects do not always coincide. To establish the nature of the species boundary within a local bacterial population, we characterized a sympatric population of the bacterium Rhizobium leguminosarum by genomic sequencing of 72 isolates. Although all strains have 16S rRNA typical of R. leguminosarum, they fall into five genospecies by the criterion of average nucleotide identity (ANI). Many genes, on plasmids as well as the chromosome, support this division: recombination of core genes has been largely within genospecies. Nevertheless, variation in ecological properties, including symbiotic host range and carbon-source utilization, cuts across these genospecies, so that none of these phenotypes is diagnostic of genospecies. This phenotypic variation is conferred by mobile genes. The genospecies meet the Mayr criteria for biological species in respect of their core genes, but do not correspond to coherent ecological groups, so periodic selection may not be effective in purging variation within them. The population structure is incompatible with traditional 'polyphasic taxonomy' that requires bacterial species to have both phylogenetic coherence and distinctive phenotypes. More generally, genomics has revealed that many bacterial species share adaptive modules by horizontal gene transfer, and we envisage a more consistent taxonomic framework that explicitly recognizes this. Significant phenotypes should be recognized as 'biovars' within species that are defined by core gene phylogeny

    The Elephant Evolved p53 Isoforms that Escape MDM2-Mediated Repression and Cancer

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    The p53 tumor suppressor is a transcription factor with roles in cell development, apoptosis, oncogenesis, aging, and homeostasis in response to stresses and infections. p53 is tightly regulated by the MDM2 E3 ubiquitin ligase. The p53-MDM2 pathway has coevolved, with MDM2 remaining largely conserved, whereas the TP53 gene morphed into various isoforms. Studies on prevertebrate ancestral homologs revealed the transition from an environmentally induced mechanism activating p53 to a tightly regulated system involving cell signaling. The evolution of this mechanism depends on structural changes in the interacting protein motifs. Elephants such as Loxodonta africana constitute ideal models to investigate this coevolution as they are large and long-living as well as having 20 copies of TP53 isoformic sequences expressing a variety of BOX-I MDM2-binding motifs. Collectively, these isoforms would enhance sensitivity to cellular stresses, such as DNA damage, presumably accounting for strong cancer defenses and other adaptations favoring healthy aging. Here we investigate the molecular evolution of the p53-MDM2 system by combining in silico modeling and in vitro assays to explore structural and functional aspects of p53 isoforms retaining the MDM2 interaction, whereas forming distinct pools of cell signaling. The methodology used demonstrates, for the first time that in silico docking simulations can be used to explore functional aspects of elephant p53 isoforms. Our observations elucidate structural and mechanistic aspects of p53 regulation, facilitate understanding of complex cell signaling, and suggest testable hypotheses of p53 evolution referencing Peto's Paradox

    1-(10,11-Di­hydro­dibenz­[b,f]­azepin-5-yl)­ethano­ne

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    The asymmetric unit of the title compound, Csb 16Hsb 15NO, comprises two independent mol-ecules (it A and it B), both adopting a half-boat conformation, or butterfly shape. The intramolecular dihedral angles between the benzene rings in it A and it B are 64.40(4) and 65.24(5)circ, respectively

    Predisposing factors for bacterial vaginosis, treatment efficacy and pregnancy outcome among term deliveries; results from a preterm delivery study

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    <p>Abstract</p> <p>Background</p> <p>Bacterial vaginosis (BV) during pregnancy is associated with an increased risk of preterm delivery but little is known about factors that could predict BV. We have analyzed if it is possible to identify a category of pregnant women that should be screened for BV, and if BV would alter the pregnancy outcome at term; we have also studied the treatment efficacy of clindamycin.</p> <p>Methods</p> <p>Prospective BV screening and treatment study of 9025 women in a geographically defined region in southeast Sweden. BV was defined as a modified Nugent score of 6 and above. Data was collected from the Swedish Medical Birth Register. Women allocated to treatment were supplied with vaginal clindamycin cream. The main outcome goals were to identify factors that could predict BV.</p> <p>Results</p> <p>Vaginal smears were consistent with BV criteria in 9.3%. Logistic regression indicates a significant correlation between smoking and BV (p < 0.001) and a greater prevalence of BV in the lower age groups (p < 0.001). We found no correlation between BV and history of preterm deliveries, previous miscarriages, extra-uterine pregnancies, infertility problems or reported history of urinary tract infections–factors that earlier have been associated with BV. Treatment with clindamycin cream showed a cure rate of 77%. Less than 1% of women with a normal vaginal smear in early pregnancy will develop BV during the pregnancy. There was no association between BV and the obstetric outcome among women who delivered at term. Women with BV, both treated patients and nontreated, had the same obstetric outcome at term as women with normal vaginal flora.</p> <p>Conclusion</p> <p>BV is more than twice as common among smokers, and there is a higher prevalence in the younger age group. However these two markers for BV do not suffice as a tool for screening, and considering the lack of other risk factors associated with BV, screening of all pregnant women might be a strategy to follow in a program intended to reduce the number of preterm births.</p
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