Cosmic-ray electrons and positrons are a unique probe of the propagation of cosmic rays as well as of the nature and distribution of particle sources in our Galaxy. Recent measurements of these ...particles are challenging our basic understanding of the mechanisms of production, acceleration, and propagation of cosmic rays. Particularly striking are the differences between the low energy results collected by the space-borne PAMELA and AMS-02 experiments and older measurements pointing to sign-charge dependence of the solar modulation of cosmic-ray spectra. The PAMELA experiment has been measuring the time variation of the positron and electron intensity at Earth from July 2006 to December 2015 covering the period for the minimum of solar cycle 23 (2006-2009) until the middle of the maximum of solar cycle 24, through the polarity reversal of the heliospheric magnetic field which took place between 2013 and 2014. The positron to electron ratio measured in this time period clearly shows a sign-charge dependence of the solar modulation introduced by particle drifts. These results provide the first clear and continuous observation of how drift effects on solar modulation have unfolded with time from solar minimum to solar maximum and their dependence on the particle rigidity and the cyclic polarity of the solar magnetic field.
We report here on the spatial distribution of C4, C6, and C8 perfluoroalkyl sulfonates, C6–C14 perfluoroalkyl carboxylates, and perfluorooctanesulfonamide in the Atlantic and Arctic Oceans, including ...previously unstudied coastal waters of North and South America, and the Canadian Arctic Archipelago. Perfluorooctanoate (PFOA) and perfluorooctanesulfonate (PFOS) were typically the dominant perfluoroalkyl acids (PFAAs) in Atlantic water. In the midnorthwest Atlantic/Gulf Stream, sum PFAA concentrations (∑PFAAs) were low (77–190 pg/L) but increased rapidly upon crossing into U.S. coastal water (up to 5800 pg/L near Rhode Island). ∑PFAAs in the northeast Atlantic were highest north of the Canary Islands (280–980 pg/L) and decreased with latitude. In the South Atlantic, concentrations increased near Rio de la Plata (Argentina/Uruguay; 350–540 pg/L ∑PFAAs), possibly attributable to insecticides containing N-ethyl perfluorooctanesulfonamide, or proximity to Montevideo and Buenos Aires. In all other southern hemisphere locations, ∑PFAAs were <210 pg/L. PFOA/PFOS ratios were typically ≥1 in the northern hemisphere, ∼1 near the equator, and ≤1 in the southern hemisphere. In the Canadian Arctic, ∑PFAAs ranged from 40 to 250 pg/L, with perfluoroheptanoate, PFOA, and PFOS among the PFAAs detected at the highest concentrations. PFOA/PFOS ratios (typically ≫1) decreased from Baffin Bay to the Amundsen Gulf, possibly attributable to increased atmospheric inputs. These data help validate global emissions models and contribute to understanding of long-range transport pathways and sources of PFAAs to remote regions.
Current duodenoscope reprocessing protocols are insufficient to prevent contamination and require adaptations to prevent endoscopy-associated infections (EAIs). This study aimed to investigate the ...effect of a new endoscope cleaning brush on the contamination rate of ready-to-use duodenoscopes.
This retrospective before-and-after intervention study collected duodenoscope surveillance culture results from March 2018 to June 2022. Contamination was defined as ≥1 colony-forming unit of a microorganism of gut or oral origin (MGO). In December 2020, an endoscope cleaning brush with a sweeper design was introduced as an intervention in the manual cleaning of duodenoscopes. A logistic mixed-effects model was used to study the effects of this intervention.
Data were collected from 176 culture sets before the new brush's introduction and 81 culture sets afterwards. Pre-introduction, culture sets positive with an MGO comprised 45.5% (95%CI 38.3%-52.8%; 80/176), decreasing to 17.3% (95%CI 10.6%-26.9%; 14/81) after implementation of the new brush. Compared with the former brush, duodenoscopes cleaned with the new brush had lower odds of contamination with MGOs (adjusted odds ratio 0.25, 95%CI 0.11-0.58;
=0.001) CONCLUSIONS: Use of the new brush in manual cleaning reduced contamination with MGOs and is expected to prevent EAIs. These findings should be confirmed in future prospective randomized studies.
Schistosomiasis is a neglected tropical disease that affects millions of people worldwide. Thioredoxin glutathione reductase of Schistosoma mansoni (SmTGR) is a validated drug target that plays a ...crucial role in the redox homeostasis of the parasite. We report the discovery of new chemical scaffolds against S. mansoni using a combi-QSAR approach followed by virtual screening of a commercial database and confirmation of top ranking compounds by in vitro experimental evaluation with automated imaging of schistosomula and adult worms. We constructed 2D and 3D quantitative structure–activity relationship (QSAR) models using a series of oxadiazoles-2-oxides reported in the literature as SmTGR inhibitors and combined the best models in a consensus QSAR model. This model was used for a virtual screening of Hit2Lead set of ChemBridge database and allowed the identification of ten new potential SmTGR inhibitors. Further experimental testing on both shistosomula and adult worms showed that 4-nitro-3,5-bis(1-nitro-1H-pyrazol-4-yl)-1H-pyrazole (LabMol-17) and 3-nitro-4-{(4-nitro-1,2,5-oxadiazol-3-yl)oxymethyl}-1,2,5-oxadiazole (LabMol-19), two compounds representing new chemical scaffolds, have high activity in both systems. These compounds will be the subjects for additional testing and, if necessary, modification to serve as new schistosomicidal agents.
Before their exocytotic release during stimulation of nerve terminals, nonpeptide neurotransmitters are loaded into synaptic vesicles by specific transporters. Recently, a protein initially ...identified as brain-specific Na(+)-dependent inorganic phosphate transporter I (BNPI) has been shown to represent a vesicular glutamate transporter (VGLUT1). In this study, we investigated whether a highly homologous "differentiation-associated Na(+)-dependent inorganic phosphate transporter" (DNPI) is involved in glutamatergic transmission. Vesicles isolated from BON cells expressing recombinant DNPI accumulated l-glutamate with bioenergetical and pharmacological characteristics identical to those displayed by VGLUT1 and by brain synaptic vesicles. Moreover, DNPI localized to synaptic vesicles, at synapses exhibiting classical excitatory features. DNPI thus represents a novel vesicular glutamate transporter (VGLUT2). The distributions of each VGLUT transcript in brain were highly complementary, with only a partial regional and cellular overlap. At the protein level, we could only detect either VGLUT1- or VGLUT2-expressing presynaptic boutons. The existence of two VGLUTs thus defines distinct subsets of glutamatergic neurons.
The energy spectra of galactic cosmic rays carry fundamental information regarding their origin and propagation. These spectra, when measured near Earth, are significantly affected by the solar ...magnetic field. A comprehensive description of the cosmic radiation must therefore include the transport and modulation of cosmic rays inside the heliosphere. During the end of the last decade, the Sun underwent a peculiarly long quiet phase well suited to study modulation processes. In this paper we present proton spectra measured from 2006 July to 2009 December by PAMEFA. The large collected statistics of protons allowed the time variation to be followed on a nearly monthly basis down to 400 MV. Data are compared with a state-of-the-art three-dimensional model of solar modulation.
ABSTRACT The cosmic-ray hydrogen and helium (1H, 2H, 3He, 4He) isotopic composition has been measured with the satellite-borne experiment PAMELA, which was launched into low-Earth orbit on board the ...Resurs-DK1 satellite on 2006 June 15. The rare isotopes 2H and 3He in cosmic rays are believed to originate mainly from the interaction of high-energy protons and helium with the galactic interstellar medium. The isotopic composition was measured between 100 and 1100 MeV/n for hydrogen and between 100 and 1400 MeV/n for helium isotopes using two different detector systems over the 23rd solar minimum from 2006 July to 2007 December.
Analog computing is based upon using physical processes to solve formal mathematical problems. In the past, it was the predominant instrument of scientific calculations. Now, as the physical limits ...imposed on digital devices compel research into alternate computing paradigms, a reexamination of the potentialities of analog computing is warranted. This work studies the application of analog CMOS cells toward the simulation of dynamical systems, and, more generally, solving sets of coupled time-dependent ordinary differential equations. Following a brief review of the fundamentals of systems theory and analog computing, the main set of computing elements is introduced, each comprising analog cells designed in a 130 nm process. These are subsequently applied to the realization of practical, special-purpose analog computing modules. Illustrative systems from various fields are selected for simulation. Though by no means comprehensive, these case studies highlight the capabilities of contemporary analog computing, especially in solving nonlinear problems. Circuit simulations show good agreement with solutions obtained from high-order numerical methods, at least over a limited range of system parameters. The article concludes with a brief discussion of broader analog computing applications, offering future prospects toward further exploration of its potentialities and limitations in a wide range of domains.
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