Healthcare-associated infections due to multidrug-resistant Gram-negative bacteria (MDR-GNB) are a leading cause of morbidity and mortality worldwide. These evidence-based guidelines have been ...produced after a systematic review of published studies on infection prevention and control interventions aimed at reducing the transmission of MDR-GNB. The recommendations are stratified by type of infection prevention and control intervention and species of MDR-GNB and are presented in the form of ‘basic’ practices, recommended for all acute care facilities, and ‘additional special approaches’ to be considered when there is still clinical and/or epidemiological and/or molecular evidence of ongoing transmission, despite the application of the basic measures. The level of evidence for and strength of each recommendation, were defined according to the GRADE approach.
H.E.S.S. has recently completed the first systematic survey of the Galactic plane in the TeV energy domain. We analyze the flux, latitude, and longitude distributions of γ-ray sources observed by ...H.E.S.S. in order to infer the properties of the Galactic TeV source population. We show that the total Milky Way luminosity in the 1-100 TeV energy range is . Evaluating the cumulative flux expected at Earth by the considered population, we show that H.E.S.S. unresolved sources provide a relevant contribution to the diffuse Galactic emission. Finally, in the hypothesis that the majority of bright sources detected by H.E.S.S. are powered by pulsar activity, like, e.g., pulsar wind nebulae or TeV halos, we estimate the main properties of the pulsar population.
A context effect is a change in preference that occurs when alternatives are added to a choice set. Models of preferential choice that account for context effects largely assume a within-dimension ...comparison process. It has been shown, however, that the format in which a choice set is presented can influence comparison strategies. That is, a by-alternative or by-dimension grouping of the dimension values encourage within-alternative or within-dimension comparisons, respectively. For example, one classic context effect, the compromise effect, is strengthened by a by-dimension presentation format. Extrapolation from this result suggests that a second context effect, the similarity effect, will actually reverse when stimuli are presented in a by-dimension format. In the current study, we presented participants with a series of apartment choice sets designed to elicit the similarity effect, with either a by-alternative or by-dimension presentation format. Participants in the by-alternative condition demonstrated a standard similarity effect; however, participants in the by-dimension condition demonstrated a strong reverse similarity effect. The present data can be accounted for by Multialternative Decision Field Theory (MDFT) and the Multiattribute Linear Ballistic Accumulator (MLBA), but not Elimination by Aspects (EBA). Indeed, when some weak assumptions of within-dimension processes are met, MDFT and the MLBA predict the reverse similarity effect. These modeling results suggest that the similarity effect is governed by either forgetting and inhibition (MDFT), or attention to positive or negative differences (MLBA). These results demonstrate that flexibility in the comparison process needs to be incorporated into theories of preferential choice.
This article studies the mechanisms of electrochemical production of ferrate (VI) using a boron-doped diamond (BDD) electrode. Ferrate was synthesized using different current densities, electrolysis ...time and concentrations of Fe(NO3)3, FeSO4, FeCl3 and FeCl2. The ferrate generation rate was highly affected by the initial concentration and the type of iron salt. The results suggest that diffusion is the controlling mechanism at the BDD electrode. However, for iron salts with oxidation state +2, electron charge also takes place. Cyclic voltammetries showed that the oxidation peak that correlated with ferrate generation is close to the potential where •OH radicals occur. This indicates that a direct electron transfer from the BDD and an indirect oxidation through •OH radicals influenced the generation of ferrate. Although Fe(NO3)3 and FeSO4 oxidation does not perform as well as iron chloride salts in the generation of ferrate, they do not form chlorate and perchlorate. This study demonstrates that it is possible to produce a powerful oxidant that could be used for water treatment purposes without generating toxic by-products.
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•The concentration of the iron salts plays a major role in ferrate production.•Diffusion and electron charge-controlling mechanisms influence ferrate generation.•Chloride radicals have a strong impact in the concentration of ferrate.•Sulfate radicals do not contribute with the electro-generation of ferrate.
An additional copy of the β-amyloid precursor protein (APP) gene causes early-onset Alzheimer's disease (AD) in trisomy 21 (DS). Endosome dysfunction develops very early in DS and AD and has been ...implicated in the mechanism of neurodegeneration. Here, we show that morphological and functional endocytic abnormalities in fibroblasts from individuals with DS are reversed by lowering the expression of APP or β-APP-cleaving enzyme 1 (BACE-1) using short hairpin RNA constructs. By contrast, endosomal pathology can be induced in normal disomic (2N) fibroblasts by overexpressing APP or the C-terminal APP fragment generated by BACE-1 (βCTF), all of which elevate the levels of βCTFs. Expression of a mutant form of APP that cannot undergo β-cleavage had no effect on endosomes. Pharmacological inhibition of APP γ-secretase, which markedly reduced Aβ production but raised βCTF levels, also induced AD-like endosome dysfunction in 2N fibroblasts and worsened this pathology in DS fibroblasts. These findings strongly implicate APP and the βCTF of APP, and exclude Aβ and the αCTF, as the cause of endocytic pathway dysfunction in DS and AD, underscoring the potential multifaceted value of BACE-1 inhibition in AD therapeutics.
•Electrochemical removal of anionic surfactant using a graphite-felt cathode was studied.•We examine the influence of the main operating parameters affecting the treatment.•Kinetic of surfactant ...oxidation was monitored.
The degradation of sodium dodecyl benzene sulfonate (LAS), a common industrial and household anionic surfactant, has been investigated by electro-Fenton process at constant current. The electrolyses have been performed using an undivided cell equipped with a Ti/RuO2 anode and a commercial graphite-felt to electrogenerate in situ hydrogen peroxide and regenerate ferrous ions as catalyst. The effect of operating conditions such as applied current, catalyst concentration, initial surfactant concentration and initial pH has been studied. Surfactant decay kinetic was monitored during the electrolysis by UV–vis measurements.
The experimental results showed that LAS was completely removed by the reaction with OH radicals generated from electrochemically assisted Fenton’s reaction, and the decay kinetics always follow a pseudo-first-order reaction. With our cell design, the higher oxidation rate has been obtained applying a current of 200mA, at pH 3 and in the presence of 0.3mM Fe2+ as catalyst. In these conditions, after 180min of electrolysis almost complete oxidation of 50mgdm−3 of LAS has been obtained with a specific energy consumption of 9.53±0.5kWhm−3.
Background Endocytic dysfunction and neurotrophin signaling deficits may underlie the selective vulnerability of hippocampal neurons during the progression of Alzheimer's disease (AD), although there ...is little direct in vivo and biochemical evidence to support this hypothesis. Methods Microarray analysis of hippocampal CA1 pyramidal neurons acquired via laser capture microdissection was performed using postmortem brain tissue. Validation was achieved using real-time quantitative polymerase chain reaction and immunoblot analysis. Mechanistic studies were performed using human fibroblasts subjected to overexpression with viral vectors or knockdown via small interference RNA. Results Expression levels of genes regulating early endosomes ( rab5 ) and late endosomes ( rab7 ) are selectively upregulated in homogeneous populations of CA1 neurons from individuals with mild cognitive impairment and AD. The levels of these genes are selectively increased as antemortem measures of cognition decline during AD progression. Hippocampal quantitative polymerase chain reaction and immunoblot analyses confirmed increased levels of these transcripts and their respective protein products. Elevation of select rab GTPases regulating endocytosis paralleled the downregulation of genes encoding the neurotrophin receptors TrkB and TrkC. Overexpression of rab5 in cells suppressed TrkB expression, whereas knockdown of TrkB expression did not alter rab5 levels, suggesting that TrkB downregulation is a consequence of endosomal dysfunction associated with elevated rab5 levels in early AD. Conclusions These data support the hypothesis that neuronal endosomal dysfunction is associated with preclinical AD. Increased endocytic pathway activity, driven by elevated rab GTPase expression, may result in long-term deficits in hippocampal neurotrophic signaling and represent a key pathogenic mechanism underlying AD progression.
The cellular protein-protein interaction network that governs cellular proliferation (cell cycle) is highly complex. Here, we have developed a novel computational model of human mitotic cell cycle, ...integrating diverse cellular mechanisms, for the purpose of generating new hypotheses and predicting new experiments designed to help understand complex diseases. The pathogenic state investigated is infection by a human herpesvirus. The model starts at mitotic entry initiated by the activities of Cyclin-dependent kinase 1 (CDK1) and Polo-like kinase 1 (PLK1), transitions through Anaphase-promoting complex (APC/C) bound to Cell division cycle protein 20 (CDC20), and ends upon mitotic exit mediated by APC/C bound to CDC20 homolog 1 (CDH1). It includes syntheses and multiple mechanisms of degradations of the mitotic proteins. Prior to this work, no such comprehensive model of the human mitotic cell cycle existed. The new model is based on a hybrid framework combining Michaelis-Menten and mass action kinetics for the mitotic interacting reactions. It simulates temporal changes in 12 different mitotic proteins and associated protein complexes in multiple states using 15 interacting reactions and 26 ordinary differential equations. We have defined model parameter values using both quantitative and qualitative data and using parameter values from relevant published models, and we have tested the model to reproduce the cardinal features of human mitosis determined experimentally by numerous laboratories. Like cancer, viruses create dysfunction to support infection. By simulating infection of the human herpesvirus, cytomegalovirus, we hypothesize that virus-mediated disruption of APC/C is necessary to establish a unique mitotic collapse with sustained CDK1 activity, consistent with known mechanisms of virus egress. With the rapid discovery of cellular protein-protein interaction networks and regulatory mechanisms, we anticipate that this model will be highly valuable in helping us to understand the network dynamics and identify potential points of therapeutic interventions.
In the present paper, the electrocatalytic abatement of urea in aqueous solutions has been studied by means of cyclic voltammetry and galvanostatic electrolysis, using different anodes such as Pt, ...Ti–Ru oxide, boron-doped diamond (BDD) and antimony-doped tin oxide. HPLC analysis, total organic carbon (TOC) and ionic chromatography have been used to evaluate the oxidation and the mineralization of the treated aqueous solutions. The results of the cyclic voltammetries have shown that, in the case of Pt and Ti–Ru oxides a decrease in current density in the oxygen evolution region can be observed in the presence of urea, due to the blockage of the electrode active oxygen evolution sites as a consequence of the reversible adsorption of urea. Instead, a notable increase in the current density has been observed in the region of the oxygen evolution for the BDD and antimony-doped tin oxide electrodes, in the presence of urea, indicating that the oxidation of urea involves hydroxyl radicals.
The bulk electrolysis tests have shown that the complete removal of urea and TOC can only be achieved using a boron-doped diamond and that Pt, the Ti–Ru oxide and antimony-doped tin oxide only permit a partial oxidation of urea. On the basis of the TOC evolution and the identification of the organic intermediates and inorganic ions released during the treatment, a total mineralization has been proposed. Finally, electrolysis has been performed in the presence of chloride ions, which act as oxidation mediator, and a comparison has been done between direct and mediated electro-oxidation.
•The electrochemical oxidation of urea has been studied on different anode materials.•Complete removal of urea and TOC using a boron-doped diamond electrode•Differences in N2 formation proved from a comparison at different current densities
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