3D simulation of conductive nanofilaments in multilayer h-BN memristors via a circuit breaker approach.

A 3D simulation of conductive nanofilaments (CNFs) in multilayer hexagonal-BN memristors is performed. To do so, a simulation tool based on circuit breakers is developed including for the first time a 3D resistive network. The circuit breakers employed can be modeled with two, three and four resistance states; in addition, a series resistance and a module to account for quantum effects, by means of the quantum point contact model, are also included. Finally, to describe real dielectric situations, regions with a high defect density are modeled with a great variety of geometrical shapes to consider their influence in the resistive switching (RS) process. The simulator has been tuned with measurements of h-BN memristive devices, fabricated with chemical-vapour-deposition grown h-BN layers, which were electrically and physically characterized. We show the formation of CNFs that produce filamentary charge conduction in our devices. Moreover, the simulation tool is employed to describe partial filament rupture in reset processes and show the low dependence of the set voltage on the device area, which is seen experimentally.

PD1/PD-L1 immune checkpoint as a potential target for preventing brain tumor progression.

Programmed death-1 (PD-1) is a cell surface receptor that functions as a T cell checkpoint and plays a central role in regulating T cell collapse. The binding of PD-1 to its ligand programmed death-ligand 1 (PD-L1) activates downstream signaling pathways and inhibits T cell activation in the perspective of immune system mechanism and regulation in tumor progression. It is well reported that tumors adopt certain immune-checkpoint pathways as a mechanism of resistance against immune cells such as T cells that are specific for tumor antigens. Indeed, the PD-1/PD-L1 pathway controls the induction and maintenance of immune tolerance within the tumor microenvironment. Thus, the PD-1/PD-L1 checkpoint regulation appears to be of extreme importance as well as the immunotherapy targeting that via and the using of PD-1/PD-L1 inhibitors that have changed the scenario of brain cancer treatment and survival. Here, we review the mechanism of action of PD-1 and PD-L1, the PD/PDL-1 signaling pathway involved in the progression of brain tumors, and its application as cancer immunotherapy counteracting tumor escape in central nervous system.

Protective effect of sodium propionate in Aß1-42 -induced neurotoxicity and spinal cord trauma.

Sodium propionate (SP) is one of the main short chain fatty acids (SCFA) that can be produced naturally through host metabolic pathways. SP have been documented and include the reduction of pro-inflammatory mediators in an in vivo model of colitis. The aim of this study is to evaluate the neuroprotective effects of SP in reducing inflammatory process associated to neurological disorders. We performed both in vitro model of Alzheimer's disease, induced by oligomeric Aß1-42 stimulation, and in in vivo model of spinal cord injury (SCI) in which neuroinflammation plays a crucial role. For in vitro model, the human neuroblastoma SH-SY5Y cell line was first differentiated with retinoic acid (100 µM) for 24 h and then stimulated by oligomeric Aß1-42 (1 µg/ml) and treated with SP at 0.1- 1-10 µM concentrations for another 24 h. Instead, the in vivo model of SCI was induced by extradural compression of the spinal cord at T6-T8 levels, and animals were treated with SP (10-30-100 mg/kg o.s) 1 and 6 h after SCI. Our results demonstrated that both in in vitro neuroinflammatory model and in vivo model of SCI the treatment with SP significantly reduced NF-κB nuclear translocation and IκBα degradation, as well as decreases COX-2 and iNOS expressions evaluated by Western blot analysis. Moreover, we showed that SP treatment significantly ameliorated histopathology changes and improved motor recovery in a dose-dependent manner. In conclusion, our results demonstrated that SP possesses neuroprotective effects, suggesting it could represent a target for therapeutic intervention in neuroinflammatory disorders.

Assessment of prevalence and load of torquetenovirus viraemia in a large cohort of healthy blood donors.

OBJECTIVES: Torquetenovirus (TTV) is an emerging marker of functional immune competence with the potential to predict transplant-related adverse events. A large-scale epidemiological study was performed to understand how basal values vary in healthy individuals according to age and gender. METHODS: We tested plasma from 1017 healthy blood donors aged 18-69 years. The presence and load of TTV were determined by a real-time PCR assay. A sub-cohort of 384 donors was tested for anti-cytomegalovirus IgG antibodies, and 100 participants were also tested for TTV viraemia on a paired whole blood sample. RESULTS: The overall prevalence of TTV was 65% (657/1017) with a mean (±SD) growth of 5 ± 4% every 10 years of age increase, but stably higher in males (465/690, 67%) than in females (192/327, 59%). Mean (±SD) TTV load was 2.3 ± 0.7 Log copies/mL with no sex difference. TTV viraemia showed modest increases along 10-year age intervals (mean ± SD: 0.3 ± 0.1). TTV viraemia in donors sampled 2 years later remained stable (mean ± SD: 2.3 ± 0.8 versus 2.2 ± 0.7 Log copies between samples). Twenty-six per cent (9/34) of blood donors with TTV-negative plasma scored positive when whole blood was tested, and the donors with positive plasma showed a mean (±SD) 1.4 ± 0.5 Log increase in copy numbers when whole blood was tested. CONCLUSIONS: This study establishes the mean value of TTV viraemia in plasma in healthy blood donors and suggests that ageing causes only minimal increases in TTV viraemia.

Peak of neuromuscular activation and angle where it occurs during bench press exercise performed with different repetition number and duration in resistance trained individuals.

The present study compared neuromuscular activation, measured by surface electromyography (EMG) amplitude [measure by EMG peak (EMGPEAK)] and range of motion (ROM) where EMGPEAK occurred between two training protocols, matched by time under tension, but with a different number and duration of repetitions. Sixteen recreationally trained males performed 2 training protocols with 3 sets, 180 s of rest with 60% of one-repetition maximum(1RM) on the bench press performed in a Smith machine. Protocol A consisted of 6 repetitions with a repetition duration of 6 s and protocol B consisted of 12 repetitions with a repetition duration of 3 s. EMG activity of anterior deltoid, pectoralis major and triceps brachii muscles were recorded. The results showed a general higher EMG amplitude (regardless of the muscle) in protocol B (p = 0.010), and pectoral and triceps brachii consistently presented higher neuromuscular activation than anterior deltoid at both protocols (p = 0.007). Additionally, the ROM where EMGPEAK occurred in triceps brachii was in the middle of the concentric action (~50% of ROM), this occurred in the first half of the same action (~24% of ROM) in the other muscles. In conclusion, protocol B demonstrated an increased EMG amplitude over protocol A, although both protocols responded similarly by achieving the highest EMG amplitude at same ROM among the muscles analysed.

Effect of different dietary tannin extracts on lamb growth performances and meat oxidative stability: comparison between mimosa, chestnut and tara.

Little information is available on the effects of different sources of tannins on ruminant product quality. Nowadays several tannin-rich extracts, produced from different plants, are available and contain tannins belonging to different chemical groups, but most of these have not been used so far as feed supplements. The present study aimed at comparing the effects of feeding three tannin extracts (one containing condensed tannins and two containing hydrolysable tannins) to lambs on growth performances and meat oxidative stability. Comisana male lambs were divided into four groups (n=9 each) and were fed for 75 days: a concentrate-based diet (CON), or CON supplemented with 4% tannin extracts from either mimosa ( MI; Acacia mearnsii, De Wild; condensed tannins), chestnut (CH; Castanea sativa, Mill; hydrolysable ellagitannins) or tara (TA; Cesalpinia spinosa, (Molina) Kuntze; hydrolysable gallotannins). Only CH reduced growth rate, final weight, carcass weight and feed intake (P0.05). The TA diet increased (P<0.001) the concentration of γ-tocopherol in muscle and tended to increase that of α-tocopherol (P=0.058). Oxidative stability of raw and cooked meat, or of meat homogenates incubated with pro-oxidants, was not affected by the extracts. These results, compared with those reported in the literature, highlight that some effects of tannins cannot be easily generalized, but may strictly depend on their specific characteristics and on conditions inherent to the basal diet and the metabolic status of the animals.

Sodium Butyrate Exerts Neuroprotective Effects in Spinal Cord Injury.

Sodium butyrate (SB) is a dietary microbial fermentation product and serves as an important neuromodulator in the central nervous system. Recent experimental evidence has suggested potential therapeutic applications for butyrate, including its utility in treating metabolic and inflammatory diseases. The aim of the present study was to evaluate the potential beneficial effects of SB in a mouse model of spinal cord injury (SCI) and its possible mechanism of action. SCI was induced by extradural compression for 1 min of the spinal cord at the T6-7 level using an aneurysm clip, and SB (10-30-100 mg/kg) was administered by oral gavage 1 and 6 h after SCI. For locomotor activity, study mice were treated with SB once daily for 10 days. Morphological examination was performed by light microscopy through hematoxylin-eosin (H&E) staining. In addition, NF-κB, IκB-α, COX-2, and iNOS expressions were assayed by western blot analysis and IL-1ß and TNF-α levels by immunohistochemistry analysis. The results showed that SB treatment significantly ameliorated histopathology changes and improved recovery of motor function changes in spinal cord injury in a dose-dependent manner. Moreover, we demonstrated that SB modulated the NF-κB pathway showing a significant reduction in cytokine expression. Thus, this study showed that SB exerts neuroprotective effects anti-inflammatory properties following spinal cord injury suggesting that SB may serve as a potential candidate for future treatment of spinal cord injury.

Electrochemical dewatering for the removal of hazardous species from sludge.

This work focuses on the evaluation of the electrochemical dewatering of sludge polluted with model hazardous species. To do this, two sludge samples taken from the outlet of the anaerobic digesters of the municipal Wastewater Treatment Facility of Ciudad Real were polluted with herbicide clopyralid (CP) and with antibiotics amoxicillin (AMX) and ampicillin (AMP), respectively. These sludge samples underwent first dewatering by press filtration and then, the dewatering continued by the application of an electrochemically assisted driven process with increasing electric fields (1.0, 2.0 and 3.0 V cm-1). Results demonstrate that the electrochemically-assisted process can help to exhaust the pollutant adsorbed onto the sludge and attain a supplemental removal (up to 15%) of water in both cases. This is a highly important result, because it can help to develop technologies for sludge treatment that avoid the diffusion of hazardous pollution during the land application of the sludge. No reactivity of the pollutants was observed during the tests.

Application and stability of cathodes with manganese dioxide nanoflowers supported on Vulcan by Fenton systems for the degradation of RB5 azo dye.

This work describes the electrochemical degradation of Reactive Black 5 (RB5) by two methods: electrochemical and photo-assisted electrochemical degradation with and without a Fenton reagent. Two anodes were used, Pt and boron-doped diamond (BDD, 2500 ppm), and the cathode was 3% MnO2 nanoflowers (NFMnO2) on a carbon gas diffusion electrode (GDE). An electrochemical cell without a divider with a GDE with 3% w/w NFMnO2/C supported on carbon Vulcan XC72 was used. The decolorization efficiency was monitored by UV-vis spectroscopy, and the degradation was monitored by Total Organic Carbon (TOC) analysis. For dissolution monitoring, aliquots (1 mL) were collected during the degradation. After 6 h of H2O2 electrogeneration, the manganese concentration in the RB5 solution was only 23.1 ±â€¯1.2 µg L-1. It was estimated that approximately 60 µg L-1 (<0.2%) of manganese migrated from the GDE to the solution after 12 h of electrolysis, which indicated the good stability of the GDE. The photoelectro-Fenton-BDD (PEF-BDD) processes showed both the best color removal percentage (∼93%) and 91% of mineralization. The 3% NFMnO2/C GDE is promising for RB5 degradation.

Repeated roll-to-roll transfer of two-dimensional materials by electrochemical delamination.

Two-dimensional (2D) materials such as graphene (Gr), molybdenum disulfide and hexagonal boron nitride (hBN) hold great promise for low-cost and ubiquitous electronics for flexible displays, solar cells or smart sensors. To implement this vision, scalable production, transfer and patterning technologies of 2D materials are needed. Recently, roll-to-roll (R2R) processing, a technique that is widely used in industry and known to be cost-effective and scalable, was applied to continuously grow and transfer graphene. However, more work is needed to understand the possibilities and limitations of this technology to make R2R processing of 2D materials feasible. In this work, we fabricated a custom R2R transferring system that allows the accurate control of the process parameters. We employ continuous electrochemical delamination, known as "bubble transfer", to eliminate chemical etchant waste and enable the continuous transfer of 2D materials from metal foils. This also makes our transfer method a renewable and environmentally friendly process. We investigate the surface topology as well as the electrical parameters of roll-to-roll transferred graphene on polyethylene terephthalate (PET) coated with ethylene-vinyl acetate (EVA). Furthermore, we demonstrate for the first time the stacking of two layers of graphene or graphene on hBN by repeated lamination and delamination onto EVA/PET. These results are an important contribution to creating low-cost, large scale and flexible electronics based on 2D materials.

Reaching a Vapor Sensitivity of 0.01 Parts Per Quadrillion in the Screening of Large Volume Freight.

The feasibility of detecting explosives in the atmosphere at concentrations as low as 0.01 ppq hinges on the poorly known question of what interfering species exist at these or higher concentrations. To clarify the issue, hundreds of samples of ambient air, either clean or loaded with explosives (from lightly contaminated environments) have been collected in fiberglass/stainless steel filters coated with Tenax-GR, thermally desorbed at variable temperature, and ionized with Cl- via secondary electrospray (SESI). They are analyzed with a narrow-band mobility filter (SEADM's P5 DMA) and a triple quadrupole mass spectrometer (Sciex's 5500), configured in series to transmit precursor and fragment ions of the explosives Nitroglycerin, PETN, RDX, and TNT. Blanks were sampled outdoors at a rural site (Boecillo, Valladolid, Spain), and loads were sampled at diverse locations. For RDX and TNT, atmospheric background inhibits detection below 1 part/trillion (ppt) without mobility filtering. This interference was drastically reduced by the DMA, allowing detection up to 1 part/quadrillion (ppq). Further sensitivity increase was achieved by scanning over a mobility region several percent around that of the target explosive, to separate various isobaric compounds by Gaussian deconvolution. (i) All four MS/MS channels analyzed exhibit several background peaks within the narrow mobility intervals investigated. At least one of these interferents is much stronger than the instrument background at the explosive's mobility, making DMA separation most helpful. (ii) For Nitroglycerin and PETN the combined filtering techniques have not lowered ambient chemical noise down to 0.01 ppq. (iii) Interferents are greatly reduced for TNT and RDX, resulting in minimal chemical noise: 322 blank tests for RDX yielded mean signal of 0.0012 ppq and standard deviation σ = 0.0035 ppq (mean + 3σ detection limit of 0.01 ppq).

Vitamin E is the major contributor to the antioxidant capacity in lambs fed whole dried citrus pulp.

The aim of this study was to investigate the effect of dietary whole dried citrus pulp (DCP) on the antioxidant status of lamb tissues. In total, 17 lambs were divided into two groups and fed for 56 days: a barley-based concentrate diet (CON - eight animals), or a concentrate-based diet including 35% DCP to partially replace barley (CIT - nine animals). The CIT diet contained a double concentration of phenolic compounds than the CON diet (7.9 v. 4.0 g/kg dry matter (DM), respectively), but had no effect (P>0.05) on the overall antioxidant capacity of the hydrophilic fraction of blood plasma, liver and muscle. The CIT diet contained clearly more α-tocopherol than the CON diet (45.7 v. 10.3 mg/kg DM), which could explain the higher concentration of α-tocopherol in liver, plasma and muscle (P<0.05). The dietary treatment had no effect on the extent of lipid peroxidation, measured as thiobarbituric acid and reactive substances assay (TBARS values) in the faeces, small intestine, liver, plasma and muscle. Nevertheless, when muscle homogenates were incubated in the presence of Fe3+/ascorbate to induce lipid peroxidation, the muscle from lambs fed DCP displayed lower TBARS values (P<0.01), which negatively correlated with the concentration of α-tocopherol in muscle. These results showed that feeding whole DCP to ruminants increases the antioxidant status of muscle through an increase in the deposition of α-tocopherol.

Near fatal asthma: treatment and prevention.

Near-fatal asthma (NFA) is described as acute asthma associated with a respiratory arrest or arterial carbon dioxide tension greater than 50 mmHg, with or without altered consciousness, requiring mechanical ventilation. Risk factors for near fatal asthma have not been fully elucidated. In 80-85% of all fatal events, a phenotype, characterized by eosinophilic inflammation associated with gradual deterioration occurring in patients with severe and poorly controlled asthma, has been identified. Regarding to the management, acute severe asthma remains a significant clinical problem, which needs to be identified to facilitate early and appropriate therapeutic interventions. The assessment relies on clinical signs, but additional information might be obtained from chest radiography or blood gas analysis. No investigation should delay the initiation of appropriate therapy. The goals of therapy are the maintenance of oxygenation, relief of airflow obstruction, reduction of airways edema and mucus plugging (with Increased use of medications such as beta-agonists via metered dose inhalers and nebulizers, oral and/or intravenous (other than by inhalation) corticosteroids and oral or intravenous theophylline) whereas supporting ventilation as clinically indicated. Of course, the emergency physician needs to consider the wide range of potential complications, as attention to these problems when managing severe acute asthma might significantly improve outcome. An understanding of the available agents and potential pitfalls in the management of NFA is mandatory for the emergency physician.

Application of electrokinetic soil flushing to four herbicides: A comparison.

In this work, four bench-scale plants containing soil spiked with four herbicides (2,4-Dichlorophenoxyacetic acid (2,4-D), oxyfluorfen, chlorsulfuron and atrazine) undergo treatment consisting of an electrokinetic soil flushing (EKSF). Results clearly demonstrate that efficiency of EKSF depends on the chemical characteristic of the pesticide used. The amount of pesticide collected in the anode well is more significant than that collected in the cathode wells, indicating that the electromigration is much more important than drainage by electro-osmotic flux for this application. After 15 d of treatment, the 2,4-D is the pesticide most efficiently removed (95% of removal), while chlorsulfuron is the pesticide more resilient to the treatment. Additionally, volatilization was found to be a process of the major significance in the application of electrokinetic techniques to soil polluted with herbicides and because of that it should always be taken into account in the future design of full-scale processes.

Performance of wind-powered soil electroremediation process for the removal of 2,4-D from soil.

In this work, it is studied a wind-powered electrokinetic soil flushing process for the removal of pesticides from soil. This approach aims to develop an eco-friendly electrochemical soil treatment technique and to face the in-situ treatment of polluted soils at remote locations. Herbicide 2,4 dichlorophenoxyacetic acid (2,4-D) is selected as a model pollutant for the soil treatment tests. The performance of the wind-powered process throughout a 15 days experiment is compared to the same remediation process powered by a conventional DC power supply. The wind-powered test covered many different wind conditions (from calm to near gale), being performed 20.7% under calm conditions and 17% under moderate or gentle breeze. According to the results obtained, the wind-powered soil treatment is feasible, obtaining a 53.9% removal of 2,4-D after 15 days treatment. Nevertheless, the remediation is more efficient if it is fed by a constant electric input (conventional DC power supply), reaching a 90.2% removal of 2,4-D with a much lower amount of charge supplied (49.2 A h kg(-1) and 4.33 A h kg(-1) for wind-powered and conventional) within the same operation time.

Vivax malaria in a blood donor in Spain, relapse or a new infection in a malaria non-endemic country?

Malaria is a vectorborne disease caused by protozoan of the genus Plasmodium, which can also be transmitted by the transfusion of infected red blood cells. One year after return from a travel to Honduras, a Spanish traveller developed vivax malaria. Prior to the onset of symptoms, the donor made a donation that tested non-reactive using an immunological test for malaria. Samples from the donor taken before donation and tested by serological and molecular methods were negative but positive at the time of hospital admission. The possible sources of the donors' infection, imported versus locally acquired, are discussed.

Immunohistochemical study and mRNA cytokine profile of the local immune response in cattle naturally infected with Calicophoron daubneyi.

In order to recognize the local immune response of the definitive host to Calicophoron daubneyi natural infection, an immunohistochemical study was carried out in the reticulum and rumen in 49 naturally infected cattle. The role of cytokines (IL-4 and IL-10 interleukins and IFN-γ) in the activation of specific defence mechanisms was evaluated by reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) assays to study cytokine mRNA expression. In all infected animals, CD3+ T lymphocytes seemed to be the main element of the inflammatory infiltrate in the reticular and ruminal lamina propria at the point of the parasite adhesion. Intraepithelial globule leukocytes also showed immunolabelling for CD3. Most CD3+ cells also expressed CD4 (T cell helper) antigen although sporadic CD8+-cytotoxic lymphocytes were observed. Local expression of IFN-γ was observed in damaged papillae at the site of parasite attachment and in scattered cells in the lamina propria. B cells (CD79αcy+, CD45+ and IgG+) were found constantly in relation to lymphoid aggregates. MAC387 was expressed in squamous epithelium and in macrophages of the lamina propria of affected papillae. Macrophages in this location also stained positively for CD163 and CD68. Intraepithelial Langerhans cells and macrophages located in the lamina propria showed immunopositivity for MHCII in the affected areas. RT-qPCR analysis confirmed a statistical significant increase of IFN-γ, and IL-10 expression (p<0.01) in the rumen associated with the presence of flukes. These findings suggest a predominant Th1 polarized local immune response with the probable involvement of Th regulatory cells in cattle C. daubneyi natural infection.

Fatty acid metabolism in lambs fed citrus pulp.

In the present study, we have hypothesized that replacing barley with high proportions of dried citrus pulp in a concentrate-based diet for lambs could increase the intake of unsaturated fatty acids and could reduce the rate of the ruminal biohydrogenation of PUFA, with a consequent improvement of the intramuscular fatty acid composition. To test this hypothesis, 26 Comisana lambs were divided into 3 groups and for 56 d were fed a barley-based concentrate diet (CON; 8 lambs) or 2 diets in which barley was replaced with 24% (CIT24; 9 lambs) or 35% (CIT35; 9 lambs) dried citrus pulp. An overall improvement of the fatty acid composition of LM from lambs fed citrus pulp-containing diets was found. The PUFA/SFA ratio was lower (P < 0.05) in the LM from lambs in the CON group compared with both the CIT24 and CIT35 groups. The thrombogenic index was lower (P < 0.05) in meat from lambs fed the CIT35 diet compared with those fed the CON diet. The CIT35 diet increased the proportion of C20:5 n-3 in the LM (P < 0.05), whereas the CIT24 diet enhanced that of C22:6 -3 (P < 0.05) compared with the CON diet. Some of these results might be explained considering that feeding the CIT24 and CIT35 diets increased the intake of total fatty acids (P < 0.05) and of C18:3 n-3 (P < 0.01) compared with feeding the CON treatment. On the other hand, phenolic compounds present in citrus pulp could have inhibited the ruminal biohydrogenation of PUFA. This is supported by the fact that regardless of the level of inclusion in the diet, citrus pulp increased the proportion of rumenic acid (P < 0.001) in LM compared with the CON diet. The plasma from lambs fed both CIT24 and CIT35 diets had a greater percentage of vaccenic acid (VA; < 0.001) compared with that from lambs fed the CON diet, and the CIT35 diet increased the proportion of rumenic acid in plasma compared with the CON treatment (P < 0.05). In the ruminal fluid, stearic acid (SA) tended to decrease, and the sum of CLA tended to increase (P = 0.09) with increasing level of citrus pulp in the diets. Furthermore, the SA/(SA + VA) ratio tended to be lower (P = 0.10) in the ruminal fluid from lambs fed the CIT35 diet compared with that of the CON group. In conclusion, our results support the hypothesis that replacing barley with citrus pulp in the diet of growing lambs improves intramuscular fatty acid composition and underline the need for specific studies to clarify the mechanisms by which feeding citrus pulp affects the fatty acid metabolism in ruminants.

A wind-powered BDD electrochemical oxidation process for the removal of herbicides.

In the search for greener treatment technologies, this work studies the coupling of a wind turbine energy supply with an electrolytic cell (CWTEC device) for the remediation of wastewater polluted with pesticide 2,4-dichlorophenoxyacetic acid (2,4-D). The discontinuous and unforeseeable supply of energy is the main challenge inspiring this new proposal, which aims at reducing the environmental impact of electrolytic treatment by using a green energy supply. The results obtained using the coupled technologies are compared with those obtained by powering the electrolyser with a traditional power supply with a similar current intensity. The mineralisation of wastewater can be accomplished independently of how the electrolytic cell is powered, although differences in performance are clearly observed in the total organic carbon (TOC) and 2,4-D decays. These changes can be explained in terms of the changing profile of the current intensity, which influences the concentrations of the oxidants produced and thereby the mediated electrolytic process.