The development of rainfall/runoff models involves extensive computation and the availability of different coexisting platforms, including numerical flow models and GIS for their physiographical ...characterization. In this paper we present a data-driven approach which avoids the use of GIS, but is based on a combination of Principal Component Analysis (PCA) and an Adaptive Neuro Fuzzy Inference System (ANFIS) to produce a simple and effective output flow prediction based on previous rainfall/runoff data in the catchment. The emphasis of the paper is on how to set-up an efficient data structure that produces a good output flow estimation. The PCA approach is compared to the Thiessen polygons method, requiring GIS, and we demonstrate that the former can produce a better ANFIS model, with less algorithmic complexity and improved accuracy. The combined PCA + ANFIS procedure is applied to two minor river basins in Tuscany, Italy, to demonstrate its effectiveness.
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•This paper presents a data-driven approach to flow-routing.•The rainfall/runoff relationship is modelled by a neuro-fuzzy network.•Principal components analysis is used to reduce the data dimensionality.•The resulting algorithm enhances the modelling flexibility and has good generalization capability.
In a series of water-rock reaction simulations, we assess the processes of serpentinization of harzburgite and related calcium metasomatism resulting in rodingite-type alteration, and seafloor ...carbonate chimney precipitation. At temperatures from 25 to 300°C (P = 10 to 100 bar), using either fresh water or seawater, serpentinization simulations produce an assemblage commonly observed in natural systems, dominated by serpentine, magnetite, and brucite. The reacted waters in the simulations show similar trends in composition with decreasing water-rock ratios, becoming hyper-alkaline and strongly reducing, with increased dissolved calcium. At 25°C and w/r less than ∼32, conditions are sufficiently reducing to yield H
2 gas, nickel-iron alloy and native copper. Hyperalkalinity results from OH
− production by olivine and pyroxene dissolution in the absence of counterbalancing OH
− consumption by alteration mineral precipitation except at very high pH; at moderate pH there are no stable calcium minerals and only a small amount of chlorite forms, limited by aluminum, thus allowing Mg
2+ and Ca
2+ to accumulate in the aqueous phase in exchange for H
+. The reducing conditions result from oxidation of ferrous iron in olivine and pyroxene to ferric iron in magnetite. Trace metals are computed to be nearly insoluble below 300°C, except for mercury, for which high pH stabilizes aqueous and gaseous Hg°. In serpentinization by seawater at 300°C, Ag, Au, Pd, and Pt may approach ore-forming concentrations in sulfide complexes. Simulated mixing of the fluid derived from serpentinization with cold seawater produces a mineral assemblage dominated by calcite, similar to recently discovered submarine, ultramafic rock-hosted, carbonate mineral deposits precipitating at hydrothermal vents. Simulated reaction of gabbroic or basaltic rocks with the hyperalkaline calcium- and aluminum-rich fluid produced during serpentinization at 300°C yields rodingite-type mineral assemblages, including grossular, clinozoisite, vesuvianite, prehnite, chlorite, and diopside.
Long-acting nanoformulated antiretroviral therapy (nanoART) induces a range of innate immune migratory, phagocytic and secretory cell functions that perpetuate drug depots. While recycling endosomes ...serve as the macrophage subcellular depots, little is known of the dynamics of nanoART-cell interactions. To this end, we assessed temporal leukocyte responses, drug uptake and distribution following both intraperitoneal and intramuscular injection of nanoformulated atazanavir (nanoATV). Local inflammatory responses heralded drug distribution to peritoneal cell populations, regional lymph nodes, spleen and liver. This proceeded for three days in male Balb/c mice. NanoATV-induced changes in myeloid populations were assessed by fluorescence-activated cell sorting (FACS) with CD45, CD3, CD11b, F4/80, and GR-1 antibodies. The localization of nanoATV within leukocyte cell subsets was determined by confocal microscopy. Combined FACS and ultra-performance liquid chromatography tandem mass-spectrometry assays determined nanoATV carriages by cell-based vehicles. A robust granulocyte, but not peritoneal macrophage nanoATV response paralleled zymosan A treatment. ATV levels were highest at sites of injection in peritoneal or muscle macrophages, dependent on the injection site. The spleen and liver served as nanoATV tissue depots while drug levels in lymph nodes were higher than those recorded in plasma. Dual polymer and cell labeling demonstrated a nearly exclusive drug reservoir in macrophages within the liver and spleen. Overall, nanoART induces innate immune responses coincident with rapid tissue macrophage distribution. Taken together, these works provide avenues for therapeutic development designed towards chemical eradication of human immunodeficiency viral infection.
Objectives
Vertical transmission of HIV can be effectively controlled through antenatal screening, antiretroviral treatment and the services provided during and after childbirth for mother and ...newborn. In Italy, the National Health Service guarantees universal access to prenatal care for all women, including women with HIV infection. Despite this, children are diagnosed with HIV infection every year. The aim of the study was to identify missed opportunities for prevention of mother‐to‐child transmission of HIV.
Methods
The Italian Register for HIV Infection in Children, which was started in 1985 and involves 106 hospitals throughout the country, collects data on all new cases of HIV infection in children. For this analysis, we reviewed the database for the period 2005 to 2015.
Results
We found 79 HIV‐1‐infected children newly diagnosed after birth in Italy. Thirty‐two of the mothers were Italian. During the pregnancy, only 15 of 19 women with a known HIV diagnosis were treated with antiretroviral treatment, while, of 34 women who had received an HIV diagnosis before labour began, only 23 delivered by caesarean section and 17 received intrapartum prophylaxis. In 25 mothers, HIV infection was diagnosed during pregnancy or in the peripartum period. Thirty‐one newborns received antiretroviral prophylaxis and 39 received infant formula.
Conclusions
We found an unacceptable number of missed opportunities to prevent mother‐to‐child transmission (MCTC). Eliminating HIV MTCT is a universal World Health Organization goal. Elucidating organization failures in Italy over the past decade should help to improve early diagnosis and to reach the zero transmission target in newborns.
Long-acting anti-HIV products can substantively change the standard of care for patients with HIV/AIDS. To this end, hydrophobic antiretroviral drugs (ARVs) were recently developed for parenteral ...administration at monthly or longer intervals. While shorter-acting hydrophilic drugs can be made into nanocarrier-encased prodrugs, the nanocarrier encasement must be boosted to establish long-acting ARV depots. The mixed-lineage kinase 3 (MLK-3) inhibitor URMC-099 provides this function by affecting autophagy. Here, we have shown that URMC-099 facilitates ARV sequestration and its antiretroviral responses by promoting the nuclear translocation of the transcription factor EB (TFEB). In monocyte-derived macrophages, URMC-099 induction of autophagy led to retention of nanoparticles containing the antiretroviral protease inhibitor atazanavir. These nanoparticles were localized within macrophage autophagosomes, leading to a 4-fold enhancement of mitochondrial and cell vitality. In rodents, URMC-099 activation of autophagy led to 50-fold increases in the plasma drug concentration of the viral integrase inhibitor dolutegravir. These data paralleled URMC-099-mediated induction of autophagy and the previously reported antiretroviral responses in HIV-1-infected humanized mice. We conclude that pharmacologic induction of autophagy provides a means to extend the action of a long-acting, slow, effective release of antiretroviral therapy.
Chemical equilibrium calculations on sedimentary formation waters show that the waters, as analyzed, cannot be in equilibrium with diagenetic minerals in their host rocks at the formation ...temperature. However, if alkalinity is corrected to account for organic acid anions, and if the pH and bicarbonate are corrected for CO
2 loss from the sample, chemical equilibrium between formation waters and host rock diagenetic minerals can be clearly shown for systems in the temperature range of 75 to 160°C.
Compositional reconstruction of some formation waters from published analyses is complicated by lack of analytical data for aluminum, silica, and organic acid anions. Missing aluminum and silica can be estimated by assuming equilibrium with an aluminum silicate (K-feldspar, muscovite) and quartz or chalcedony. pH, CO
2, and organic acid anions can be reconstructed by fixing CO
2 to exactly saturate calcite at the formation temperature because the fast kinetics of calcite precipitation makes it almost certain that calcite saturation is more likely than the strong supersaturation that is otherwise observed. Results from the equilibrium calculations are evaluated by using graphs of the saturation states of diagenetic minerals vs. temperature, for each of many sedimentary brines. If the diagenetic minerals selected as diagnostic of equilibrium (from qz, chalcedony, mus, paragonite, k-sp, alb, kaol, ca, and dol) are not saturated at or near a single temperature, the missing or erroneous quantities of components are adjusted to obtain agreement in the saturation temperature. Composition data for fluids from four locations are used in the calculations: Kettleman North Dome, California, offshore Norway, the Texas Gulf Coast, and offshore Texas.
The calculations suggest that in most cases, control of silica concentration shifts from chalcedony to quartz with increasing temperature near 100°C. In some fluids, silica concentration may approach chalcedony saturation to temperatures exceeding 150°C, where there are shale units containing smectite undergoing the smectite to illite reaction. Deviation in silica activity from equilibrium with chalcedony or quartz is small for most of the fluids, and may result from precipitation of silica as polymers or amorphous solids upon cooling, and either removal of precipitates upon filtering before analysis, or nonreactivity of the precipitates in the analytical method used. Four fluids containing significant iron and having apparently degassed significant CO
2 also show substantial apparent silica loss, and therefore, silica loss most probably results from the precipitation of amorphous Fe-silicate caused by pH increase due to degassing, and by cooling. The methods used here can be applied as a geothermometer to predict formation temperatures, and, when applied to Kettleman North Dome, yield a thermal gradient of 37.1°C/km. Formation temperature data for the Texas waters are in agreement with equilibrium temperatures predicted by the calculations.
Thermodynamic simulations of reactions among SO2-bearing CO2-dominated gas, water and mineral phases predict that FeIII in sediments should be converted almost entirely to dissolved FeII and siderite ...(FeCO3), and that SO2 should simultaneously be oxidized to dissolved sulfate. The reactions are however, subject to kinetic constraints which may result in deviation from equilibrium and the precipitation of other metastable mineral phases. To test the prediction, a laboratory experiment was carried out in a well stirred hydrothermal reactor at 150 degree C and 300bar with hematite, 1.0m NaCl, 0.5m NaOH, SO2 in quantity sufficient to reduce much of the iron, and excess CO2. The experiment produced stable siderite and metastable pyrite and elemental S. Changes in total dissolved Fe are consistent with nucleation of pyrite at 17h, and nucleation of siderite at 600h. Dissolution features present on elemental S at the conclusion of the experiment suggest nucleation early in the experiment. The experiment did not reach equilibrium after 1400h, as indicated by coexistence of hematite with metastable pyrite and elemental sulfur. However, the results confirm that FeIII can be used to trap CO2 in siderite if partly oxidized S, as SO2, is present to reduce the Fe with CO2 in the gas phase.
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