Space, state-building and the hydraulic mission: crafting the Mozambican State

This article explores the role of large-scale water infrastructure in the formation of states in sub-Saharan Africa. We examine this through a focus on government agents and their shifting hydro-developmental visions of the state in colonial and post-colonial Mozambique. Over time, the focus, underlying principles, and goals of the hydraulic mission shifted, triggered by contextual factors and historical developments within and outside the country. We identify the making of three hydraulic paradigms, fostering different imaginaries of ‘the state’ and social and spatial engineering of the territory: the ‘Estado Novo’ (1930 - 1974), the socialist post-independence state-space (1974 - 1987) and the neoliberal state (1987 - present). We then conclude by discussing how the shifting discursive justifications for infrastructure projects consolidate different state projects and link these to material re-patterning of hydrosocial territories, showing that whilst promoted as a rupture with the past, emerging projects tend to reaffirm, rather than redistribute, power and water within the country

Immune-Mobilizing Monoclonal T Cell Receptors Mediate Specific and Rapid Elimination of Hepatitis B-Infected Cells

Background and Aims: Therapies for chronic hepatitis B virus (HBV) infection are urgently needed because of viral integration, persistence of viral antigen expression, inadequate HBV‐specific immune responses, and treatment regimens that require lifelong adherence to suppress the virus. Immune mobilizing monoclonal T Cell receptors against virus (ImmTAV) molecules represent a therapeutic strategy combining an affinity‐enhanced T Cell receptor with an anti‐CD3 T Cell‐activating moiety. This bispecific fusion protein redirects T cells to specifically lyse infected cells expressing the target virus‐derived peptides presented by human leukocyte antigen (HLA). Approach and Results: ImmTAV molecules specific for HLA‐A*02:01‐restricted epitopes from HBV envelope, polymerase, and core antigens were engineered. The ability of ImmTAV‐Env to activate and redirect polyclonal T cells toward cells containing integrated HBV and cells infected with HBV was assessed using cytokine secretion assays and imaging‐based killing assays. Elimination of infected cells was further quantified using a modified fluorescent hybridization of viral RNA assay. Here, we demonstrate that picomolar concentrations of ImmTAV‐Env can redirect T cells from healthy and HBV‐infected donors toward hepatocellular carcinoma (HCC) cells containing integrated HBV DNA resulting in cytokine release, which could be suppressed by the addition of a corticosteroid in vitro. Importantly, ImmTAV‐Env redirection of T cells induced cytolysis of antigen‐positive HCC cells and cells infected with HBV in vitro, causing a reduction of hepatitis B e antigen and specific loss of cells expressing viral RNA. Conclusions: The ImmTAV platform has the potential to enable the elimination of infected cells by redirecting endogenous non‐HBV‐specific T cells, bypassing exhausted HBV‐specific T cells. This represents a promising therapeutic option in the treatment of chronic hepatitis B, with our lead candidate now entering trials

Diagnosis of Hepatozoon canis in young dogs by cytology and PCR

<p>Abstract</p> <p>Background</p> <p><it>Hepatozoon canis </it>is a widespread tick-borne protozoan affecting dogs. The diagnosis of <it>H. canis </it>infection is usually performed by cytology of blood or buffy coat smears, but this method may not be sensitive. Our study aimed to evaluate the best method to achieve a parasitological diagnosis of <it>H. canis </it>infection in a population of receptive young dogs, previously negative by cytology and exposed to tick infestation for one summer season.</p> <p>Results</p> <p>A total of 73 mongrel dogs and ten beagles younger than 18 months of age, living in an animal shelter in southern Italy where dogs are highly infested by <it>Rhipicephalus sanguineus</it>, were included in this study. In March-April 2009 and in October 2009, blood and bone marrow were sampled from each dog. Blood, buffy coat and bone marrow were examined by cytology only (at the first sampling) and also by PCR for <it>H. canis </it>(second sampling). In March-April 2009, only one dog was positive for <it>H. canis </it>by cytological examination, whereas in October 2009 (after the summer season), the overall incidence of <it>H. canis </it>infection by cytological examinations was 43.9%. Molecular tests carried out on samples taken in October 2009 showed a considerably higher number of dogs positive by PCR (from 27.7% up to 51.2% on skin and buffy coat tissues, respectively), with an overall positivity of 57.8%. All animals, but one, which were positive by cytology were also PCR-positive. PCR on blood or buffy coat detected the highest number of <it>H. canis</it>-positive dogs displaying a sensitivity of 85.7% for both tissues that increased up to 98% when used in parallel. Twenty-six (74.8%) out of the 28 <it>H. canis</it>-positive dogs presented hematological abnormalities, eosinophilia being the commonest alteration observed.</p> <p>Conclusions</p> <p>The results suggest that PCR on buffy coat and blood is the best diagnostic assay for detecting <it>H. canis </it>infection in dogs, although when PCR is not available, cytology on buffy coat should be preferred to blood smear evaluation. This study has also demonstrated that <it>H. canis </it>infection can spread among young dogs infested by <it>R. sanguineus </it>and be present in the majority of the exposed population within 6 months.</p

Molecular Dynamics Simulation of Phosphorylated KID Post-Translational Modification

BACKGROUND:Kinase-inducible domain (KID) as transcriptional activator can stimulate target gene expression in signal transduction by associating with KID interacting domain (KIX). NMR spectra suggest that apo-KID is an unstructured protein. After post-translational modification by phosphorylation, KID undergoes a transition from disordered to well folded protein upon binding to KIX. However, the mechanism of folding coupled to binding is poorly understood. METHODOLOGY:To get an insight into the mechanism, we have performed ten trajectories of explicit-solvent molecular dynamics (MD) for both bound and apo phosphorylated KID (pKID). Ten MD simulations are sufficient to capture the average properties in the protein folding and unfolding. CONCLUSIONS:Room-temperature MD simulations suggest that pKID becomes more rigid and stable upon the KIX-binding. Kinetic analysis of high-temperature MD simulations shows that bound pKID and apo-pKID unfold via a three-state and a two-state process, respectively. Both kinetics and free energy landscape analyses indicate that bound pKID folds in the order of KIX access, initiation of pKID tertiary folding, folding of helix alpha(B), folding of helix alpha(A), completion of pKID tertiary folding, and finalization of pKID-KIX binding. Our data show that the folding pathways of apo-pKID are different from the bound state: the foldings of helices alpha(A) and alpha(B) are swapped. Here we also show that Asn139, Asp140 and Leu141 with large Phi-values are key residues in the folding of bound pKID. Our results are in good agreement with NMR experimental observations and provide significant insight into the general mechanisms of binding induced protein folding and other conformational adjustment in post-translational modification

The Early Discovery of SN 2017ahn: Signatures of Persistent Interaction in a Fast-declining Type II Supernova

We present high-cadence, comprehensive data on the nearby (D 33 Mpc) Type II supernova (SN II) 2017ahn, discovered within about one day of the explosion, from the very early phases after explosion to the nebular phase. The observables of SN 2017ahn show a significant evolution over the 470 days of our follow-up campaign, first showing prominent, narrow Balmer lines and other high-ionization features purely in emission (i.e., flash spectroscopy features), which progressively fade and lead to a spectroscopic evolution similar to that of more canonical SNe II. Over the same period, the decline of the light curves in all bands is fast, resembling the photometric evolution of linearly declining H-rich core-collapse SNe. The modeling of the light curves and early flash spectra suggests that a complex circumstellar medium surrounds the progenitor star at the time of explosion, with a first dense shell produced during the very late stages of its evolution that is swept up by the rapidly expanding ejecta within the first similar to 6 days of the SN evolution, while signatures of interaction are observed also at later phases. Hydrodynamical models support the scenario in which linearly declining SNe II are predicted to arise from massive yellow super- or hypergiants depleted of most of their hydrogen layers

Use of vitamin supplements and risk of total cancer and cardiovascular disease among the Japanese general population: A population-based survey

<p>Abstract</p> <p>Background</p> <p>Despite the popular use of vitamin supplements and several prospective cohort studies investigating their effect on cancer incidence and cardiovascular disease (CVD), scientific data supporting their benefits remain controversial. Inconsistent results may be partly explained by the fact that use of supplements is an inconsistent behavior in individuals. We examined whether vitamin supplement use patterns affect cancer and CVD risk in a population-based cohort study in Japan.</p> <p>Methods</p> <p>A total of 28,903 men and 33,726 women in the Japan Public Health Center-based Prospective Study cohort, who answered questions about vitamin supplement use in the first survey from 1990-1994 and the second survey from 1995-1998, were categorized into four groups (never use, past use, recent use, and consistent use) and followed to the end of 2006 for cancer and 2005 for CVD. Sex-specific hazard ratios (HRs) and 95% confidence intervals (95% CIs) were used to describe the relative risks of cancer and CVD associated with vitamin supplement use.</p> <p>Results</p> <p>During follow-up, 4501 cancer and 1858 CVD cases were identified. Multivariate adjusted analysis revealed no association of any pattern of vitamin supplement use with the risk of cancer and CVD in men. In women, consistent use was associated with lower risk of CVD (HR 0.60, 95% CI 0.41-0.89), whereas past (HR 1.17, 95% CI 1.02-1.33) and recent use (HR 1.24, 95% CI 1.01-1.52) were associated with higher risk of cancer.</p> <p>Conclusions</p> <p>To our knowledge, this is the first prospective cohort study to examine simultaneously the associations between vitamin supplement use patterns and risk of cancer and CVD. This prospective cohort study demonstrated that vitamin supplement use has little effect on the risk of cancer or CVD in men. In women, however, consistent vitamin supplement use might reduce the risk of CVD. Elevated risk of cancer associated with past and recent use of vitamin supplements in women may be partly explained by preexisting diseases or unhealthy background, but we could not totally control for this in our study.</p

SN 2018gjx reveals that some SNe Ibn are SNe IIb exploding in dense circumstellar material

We present the data and analysis of SN 2018gjx, an unusual low-luminosity transient with three distinct spectroscopic phases. Phase I shows a hot blue spectrum with signatures of ionized circumstellar material (CSM), Phase II has the appearance of broad SN features, consistent with those seen in a Type IIb supernova at maximum light, and Phase III is that of a supernova interacting with helium-rich CSM, similar to a Type Ibn supernova. This event provides an apparently rare opportunity to view the inner workings of an interacting supernova. The observed properties can be explained by the explosion of a star in an aspherical CSM. The initial light is emitted from an extended CSM (∼4000 R⊙), which ionizes the exterior unshocked material. Some days after, the SN photosphere envelops this region, leading to the appearance of a SN IIb. Over time, the photosphere recedes in velocity space, revealing interaction between the supernova ejecta and the CSM that partially obscures the supernova nebular phase. Modelling of the initial spectrum reveals a surface composition consistent with compact H-deficient Wolf–Rayet and Luminous Blue Variable (LBV) stars. Such configurations may not be unusual, with SNe IIb being known to have signs of interaction so at least some SNe IIb and SNe Ibn may be the same phenomena viewed from different angles, or possibly with differing CSM configurations

SN 2018gjx reveals that some SNe Ibn are SNe IIb exploding in dense circumstellar material

We present the data and analysis of SN 2018gjx, an unusual low-luminosity transient with three distinct spectroscopic phases. Phase I shows a hot blue spectrum with signatures of ionized circumstellar material (CSM), Phase II has the appearance of broad SN features, consistent with those seen in a Type IIb supernova at maximum light, and Phase III is that of a supernova interacting with helium-rich CSM, similar to a Type Ibn supernova. This event provides an apparently rare opportunity to view the inner workings of an interacting supernova. The observed properties can be explained by the explosion of a star in an aspherical CSM. The initial light is emitted from an extended CSM (similar to 4000 R-circle dot), which ionizes the exterior unshocked material. Some days after, the SN photosphere envelops this region, leading to the appearance of a SN IIb. Over time, the photosphere recedes in velocity space, revealing interaction between the supernova ejecta and the CSM that partially obscures the supernova nebular phase. Modelling of the initial spectrum reveals a surface composition consistent with compact H-deficient Wolf-Rayet and Luminous Blue Variable (LBV) stars. Such configurations may not be unusual, with SNe IIb being known to have signs of interaction so at least some SNe IIb and SNe Ibn may be the same phenomena viewed from different angles, or possibly with differing CSM configurations

Supernova 2018cuf: A Type IIP Supernova with a Slow Fall from Plateau

We present multiband photometry and spectroscopy of SN 2018cuf, a Type IIP ("P" for plateau) supernova (SN) discovered by the Distance Less Than 40 Mpc Survey within 24 hr of explosion. SN 2018cuf appears to be a typical SN IIP, with an absolute V-band magnitude of -16.73 0.32 at maximum and a decline rate of 0.21 0.05 mag/50 days during the plateau phase. The distance of the object was constrained to be 41.8 5.7 Mpc by using the expanding photosphere method. We used spectroscopic and photometric observations from the first year after the explosion to constrain the progenitor of SN 2018cuf using both hydrodynamic light-curve modeling and late-time spectroscopic modeling. The progenitor of SN 2018cuf was most likely a red supergiant of about 14.5 M that produced 0.04 0.01 M Ni-56 during the explosion. We also found similar to 0.07 M of circumstellar material (CSM) around the progenitor is needed to fit the early light curves, where the CSM may originate from presupernova outbursts. During the plateau phase, high-velocity features at similar to 11,000 km s(-1) were detected in both the optical and near-infrared spectra, supporting the possibility that the ejecta were interacting with some CSM. A very shallow slope during the postplateau phase was also observed, and it is likely due to a low degree of nickel mixing or the relatively high nickel mass in the SN

Guidelines for diagnosis and management of the cobalamin-related remethylation disorders cblC, cblD, cblE, cblF, cblG, cblJ and MTHFR deficiency

BACKGROUND: Remethylation defects are rare inherited disorders in which impaired remethylation of homocysteine to methionine leads to accumulation of homocysteine and perturbation of numerous methylation reactions. OBJECTIVE: To summarise clinical and biochemical characteristics of these severe disorders and to provide guidelines on diagnosis and management. DATA SOURCES: Review, evaluation and discussion of the medical literature (Medline, Cochrane databases) by a panel of experts on these rare diseases following the GRADE approach. KEY RECOMMENDATIONS: We strongly recommend measuring plasma total homocysteine in any patient presenting with the combination of neurological and/or visual and/or haematological symptoms, subacute spinal cord degeneration, atypical haemolytic uraemic syndrome or unexplained vascular thrombosis. We strongly recommend to initiate treatment with parenteral hydroxocobalamin without delay in any suspected remethylation disorder; it significantly improves survival and incidence of severe complications. We strongly recommend betaine treatment in individuals with MTHFR deficiency; it improves the outcome and prevents disease when given early