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Synthetic drugs for recreational purposes are in constant evolution, and their consumption promotes a significant increase in intoxication cases, resulting in damaging public health. The development of analytical methodologies to confirm the consumption of illicit drugs in biological matrices is required for the control of these substances. This work exploited the development of an extraction method based on homogenous liquid–liquid microextraction with switchable hydrophilicity solvent (SHS) as extraction phase for the determination of the synthetic drugs 3,4-methylenedioxymethamphetamine, 3,4-methylenedioxyamphetamine and N-methoxybenzyl-methoxyphenylethylamine derivates (25B, 25C and 25I) in postmortem blood, followed by liquid chromatography coupled to mass spectrometry in tandem. The optimized sample preparation conditions consisted of using 250 µL of ZnSO4 10% and 50 µL of NaOH 1 mol/L in the protein precipitation step; N,N-dimethylcyclohexylamine was used as SHS, 650 μL of a mixture of SHS:HCl 6 mol/L (1:1 v/v), 500 μL of whole blood, 500 μL of NaOH 10 mol/L and 1 min of extraction time. The proposed method was validated, providing determination coefficients higher than 0.99 for all analytes; limit of detection and limit of quantitation ranged from 0.1 to 10 ng/mL; intra-run precision from 2.16% to 9.19%; inter-run precision from 2.39% to 9.59%; bias from 93.57% to 115.71% and matrix effects from 28.94% to 51.54%. The developed method was successfully applied to four authentic postmortem blood samples from synthetic drugs users, and it was found to be reliable with good selectivity.

Objectives To evaluate the safety and efficacy of cidofovir for the treatment of double-stranded DNA (dsDNA) viral infections following allogeneic haematopoietic cell transplant (HCT). Methods This was a retrospective multicentre cohort study including adult HCT recipients who received ≥1 dose of IV-administered cidofovir for any dsDNA viral infection from 2006 to 2019. The objectives were to describe the rate of and risk factors for nephrotoxicity and virological response by the end of treatment (EOT). Results We included 165 patients from nine centres. Cidofovir was administered at 5 mg/kg/week (N = 115; 69.7%), 1 mg/kg/week (18; 10.9%), 3 mg/kg/week (12; 7.3%) or 1 mg/kg three times/week (11; 6.7%). Cidofovir was administered for adenovirus, cytomegalovirus (CMV) and BK virus infection in 75 (45.5%), 64 (38.8%) and 51 (30.9%) patients, respectively. Among 158 patients with renal function data at baseline and EOT, 40 (25.3%) developed nephrotoxicity. In multivariable analyses, age (OR 1.04; P = 0.05), weight (OR 1.05; P = 0.01), CMV infection (OR 3.6; P = 0.02), liposomal amphotericin B (OR 8.06; P = 0.05) and IV voriconazole/posaconazole (OR 13.0; P = 0.003) were predictors of nephrotoxicity. Creatinine concentration was significantly higher at EOT (1.16 ± 0.95 mg/dL) compared with baseline (0.91 ± 0.39 mg/dL; P Conclusions One in four HCT recipients treated with IV cidofovir developed largely reversible nephrotoxicity. Careful selection of patients and close follow-up of renal function may minimize toxicity.

In this article, a new and simple way of producing sparklers is presented as a school experiment. These sparklers are more environmentally friendly and less health threatening than sparklers produced with existing preparation methods. The problem of conventional sparklers is the toxicity of barium nitrate, which is used as the oxidizer. The substitution of this oxidizer with strontium nitrate and also the reduction of the weight proportion makes the new mixture less dangerous and less toxic. Various tests for the categorization of high-energetic materials show that the newly developed sparklers are not classified as explosives. Furthermore, the tests demonstrate that the newly developed sparklers are not as dangerous as commercial sparklers. Due to their lower health risk, these new sparklers are well suited for use in school education. In addition, expenditure for this experiment is low and integrating it into the upper secondary level curriculum is easy. Sparklers are an impressive example of redox reactions from everyday life. The experiment is a best-practice application for chemistry education, incorporating current results of chemistry research.

Objectives Emerging treatments for relapsed or refractory multiple myeloma (rrMM) have led to increasing options for many patients. This study aimed to assess changes in utilization of these options in Germany with a focus on modern triplet regimens including new agents, such as carfilzomib, ixazomib, elotuzumab and daratumumab, and to evaluate whether this had an impact on rrMM‐related outcomes over time. Methods The study population consisted of 1255 rrMM patients who were assigned to one of the following 6 treatment groups: immunomodulatory drug (IMiD)‐based doublets, proteasome inhibitor (PI)‐based doublets, daratumumab monotherapy, PI‐IMiD‐based triplets, monoclonal antibodies (mAbs)‐based triplets, or other treatment. Results Use of triplet‐based therapy regimens increased from 5.9% in 2014 to 31.4% in 2017. In parallel, use of IMiD‐based doublets decreased from 74.3% in 2014 to 37.6% in 2017. Over the same time period, the risk of death decreased by 32% and the risk of hospitalization which was reduced by 30%. The risk for serious adverse events remained unchanged. Conclusions Between 2014 and 2017, the use of triplet‐based therapy regimens for rrMM in Germany has significantly increased and this was associated with a significant decline in deaths and hospitalizations without an increased incidence of serious adverse events.

Drilling fluids perform several functions such as lubrication and cooling of the drill bit, carrying the cuttings to the surface and also maintaining the stability of the well. The physicochemical characteristics of solid particles affect the drilling fluid properties, such as density, chemical composition, and surface charge. In this research, the effects of concentration, surface charge, and adsorption of different solid additives (Barite, Calcite, and Glass spheres) in carboxymethylcellulose (CMC) aqueous solutions were evaluated to quantify its influence on the apparent viscosity of drilling fluids. A study of the polymer hydration time was also carried out. The suspensions were characterized and analyzed by the rheological parameters, the morphology, the surface charge, and the chemical composition. The results showed that suspensions with solids concentration higher than 25% (m/v) presented an increase of the frictional effect of solids, leading to a significant increase in the apparent viscosity of the suspensions. The morphology of the glass spheres facilitated the fluid flow, leading to the lowest apparent viscosity among the suspensions. Ca2+ ions from calcite solids reduced the energy barrier against flocculation, making the apparent viscosity of calcite suspensions the highest. The barite suspensions showed the highest zeta potential value (in modulus) among all suspensions. The appearance of two bands related to the carbonyl in the FTIR spectrum of barite suspensions proves chemical adsorption with the CMC polymer, justifying its lower apparent viscosity compared to calcite suspensions.

We previously found that argon exerts its neuroprotective effect in part by inhibition of the toll-like receptors (TLR) 2 and 4. The downstream transcription factors signal transducer and activator of transcription 3 (STAT3) and nuclear factor kappa B (NF-κB) are also affected by argon and may play a role in neuroprotection. It also has been demonstrated that argon treatment could mitigate brain damage, reduce excessive microglial activation, and subsequently attenuate brain inflammation. Despite intensive research, the further exact mechanism remains unclear. In this study, human neuroblastoma cells were damaged in vitro with rotenone over a period of 4 hours (to mimic cerebral ischemia and reperfusion damage), followed by a 2-hour post-conditioning with argon (75%). In a separate in vivo experiment, retinal ischemia/reperfusion injury was induced in rats by increasing intraocular pressure for 1 hour. Upon reperfusion, argon was administered by inhalation for 2 hours. Argon reduced the binding of the transcription factors signal transducer and activator of transcription 3, nuclear factor kappa B, activator protein 1, and nuclear factor erythroid 2-related factor 2, which are involved in regulation of neuronal damage. Flow cytometry analysis showed that argon downregulated the Fas ligand. Some transcription factors were regulated by toll-like receptors; therefore, their effects could be eliminated, at least in part, by the TLR2 and TLR4 inhibitor oxidized phospholipid 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (OxPAPC). Argon treatment reduced microglial activation after retinal ischemia/reperfusion injury. Subsequent quantitative polymerase chain reaction analysis revealed a reduction in the pro-inflammatory cytokines interleukin (IL-1α), IL-1β, IL-6, tumor necrosis factor α, and inducible nitric oxide synthase. Our results suggest that argon reduced the extent of inflammation in retinal neurons after ischemia/reperfusion injury by suppression of transcription factors crucial for microglial activation. Argon has no known side effects or narcotic properties; therefore, therapeutic use of this noble gas appears ideal for treatment of patients with neuronal damage in retinal ischemia/reperfusion injury. The animal experiments were approved by the Commission for Animal Care of the University of Freiburg (approval No. 35-9185.81/G14-122) on October 19, 2012.

Contains fulltext : 220662.pdf (Publisher’s version ) (Closed access) The purpose of our study is to provide information on safety and efficacy of ibrutinib as salvage treatment after allo-HSCT for CLL. A total of 56 patients were included, 36 (64%) males; median age at transplantation was 48 years (range: 35-64) and the median number of treatment lines prior to transplantation was 3 (1-10). The median time between allo-HSCT and Ibrutinib was 30 months (range: 1-140). Overall, 40 (71%) patients responded to Ibrutinib; 23 (41%) PR, and 17 (30%) CR. At time of ibrutinib initiation, ten patients had active chronic GVHD that resolved under Ibrutinib, whilst a single patient developed limited de novo chronic GVHD on Ibrutinib. Fourteen patients discontinued ibrutinib, four because of toxicity and ten because of disease progression. Overall, 14 patients progressed (median PFS = 24 months) among them 10 died. Two-year OS and PFS probabilities were 72% (95% CI: 52-84) and 50% (95% CI: 32-66), respectively. Patients with late relapse after allo-HSCT (>/=24 months) had a better PFS after ibrutinib. Our study shows that ibrutinib can be safely administered for CLL relapse after allo-HSCT, with comparable efficacy to non-transplanted patients with high-risk disease.

Remarkable progress has been achieved in the application of magnetic ionic liquids in microextraction-based procedures. These materials exhibit unique physicochemical properties of ionic liquids featuring additional responses to magnetic fields by incorporating a paramagnetic component within the chemical structure. This intriguing property can open new horizons in analytical extractions because the solvent manipulation is facilitated. Moreover, the tunable chemical structures of magnetic ionic liquids also allow for task-specific extractions that can significantly increase the method selectivity. This review aimed at providing an up-to-date overview of articles involving synthesis, physicochemical properties, and applications of magnetic ionic liquids highlighting recent developments and configurations. Moreover, a section containing critical evaluation and future trends in magnetic ionic liquid-based extractions is included.

International audience; The dielectric properties of aluminium oxide (Al2O3) thin films obtained by plasma-enhanced atomic layer deposition (PEALD) from Al(CH3)3/O2 precursors were investigated while focusing on the influences of thermal annealing under a dioxygen (O2) ambient. PEALD-Al2O3-based metalinsulator-silicon structures/capacitors and pH-sensitive chemical field effect transistors were fabricated to deal respectively with microelectronic applications and measurement in liquid phase. Antagonist results were thus evidenced. On the one hand, dealing with high-k gate materials, optimized dielectric properties, i.e. low fixed charge density (4 × 10 12 cm-2), high dielectric constant (r = 10.2), Fowler-Nordheim conduction and high breakdown electric fields (Ebd = 8.75 MV/cm) were obtained for polycrystalline PEALD Al2O3 films annealed at high temperature (T > 750°C). On the other hand, pH detection properties, i.e. quasi-Nernstian sensitivity (59 mV/pH), low drift (< 1 mV/day) and long lifetime (> 180 days), were optimized for unannealed amorphous PEALD Al2O3 films. These phenomena were associated germination/crystallization phenomena in the deposited amorphous alumina structure as well as to related charge trapping and leakage currents in water-based solutions related to the final Al2O3 polycrystalline structure.

Lactose can fuel GVHD Allogeneic hematopoietic cell transplantation (allo-HCT) is used to treat certain hematopoietic malignancies, but patients have a risk of developing graft-versus-host disease (GVHD). Stein-Thoeringer et al. performed a large-scale analysis of more than 1300 patients treated with allo-HCT across four clinical centers (see the Perspective by Zitvogel and Kroemer). High levels of bacteria from the Enterococcus genus were associated with greater incidence of GVHD and mortality. Lactose appears to provide a substrate for Enterococcus growth, and patients with a lactose-malabsorption genotype had a greater abundance of Enterococcus. A lactose-free diet limited Enterococcus growth, reduced the severity of GVHD, and improved survival in gnotobiotic mouse models. Science , this issue p. 1143 ; see also p. 1077

CO2 is the most important greenhouse gas in terms of emitted quantities and its emission has increased significantly due to the action of anthropogenic sources. Among the alternatives for mitigation of this gas is the direct synthesis of propylene carbonate (PC), which requires efficient and selective catalysts. In this scenario the titanate nanotubes (TNT) are promising catalysts because they can be modified to become selective for the PC synthesis. The present work has the objective to develop titanate nanotubes with different metals (Na, Sn and Zn) as well as protonated titanate nanotubes (HTNT) and to test their efficiency in the direct synthesis of PC. The synthesized nanostructures were characterized by TEM, EDS, XRD and N2 adsorption-desorption. The results showed that the synthesized TNT have a specific surface area of 155, 232, 56 and 140 m2/g (NaTNT, HTNT, SnTNT and ZnTNT, respectively). Besides, the ion exchange of [Na+] by [Sn+2] and [Zn+2] decreased the crystallinity of nanostructure. On the catalytic tests, the system NaTNT/ZnBr2 showed the best results with a yield of 61% and a selectivity of 81% in PC. The catalytic system SnTNT/DMF and ZnTNT/DMF are promising to this reaction showing interesting yields and catalytic activity (59 and 53%; 295 and 265 mmol/g) for PC synthesis.

Utilizing a mixed Mg/Al oxide derivate from hydrotalcites as catalyst for the ethanol conversation to 1-butanol, catalytic tests were performed using a tubular quartz reactor at different reaction ...

In contrast to the light requirement for Arabidopsis seed germination, the germination of several Aethionema arabicum accessions is inhibited by light, due to antipodal transcriptional regulation of hormone balance., The timing of seed germination is crucial for seed plants and is coordinated by internal and external cues, reflecting adaptations to different habitats. Physiological and molecular studies with lettuce and Arabidopsis thaliana have documented a strict requirement for light to initiate germination and identified many receptors, signaling cascades, and hormonal control elements. In contrast, seed germination in several other plants is inhibited by light, but the molecular basis of this alternative response is unknown. We describe Aethionema arabicum (Brassicaceae) as a suitable model plant to investigate the mechanism of germination inhibition by light, as this species has accessions with natural variation between light-sensitive and light-neutral responses. Inhibition of germination occurs in red, blue, or far-red light and increases with light intensity and duration. Gibberellins and abscisic acid are involved in the control of germination, as in Arabidopsis, but transcriptome comparisons of light- and dark-exposed A. arabicum seeds revealed that, upon light exposure, the expression of genes for key regulators undergo converse changes, resulting in antipodal hormone regulation. These findings illustrate that similar modular components of a pathway in light-inhibited, light-neutral, and light-requiring germination among the Brassicaceae have been assembled in the course of evolution to produce divergent pathways, likely as adaptive traits.

The high PET consume, mainly as bottles, associated with rapid disposal and high resistance to ambient conditions and biological degradation lead to accumulation in the enviromental, constituting a worrying scenario in world level. Chemical recycle PET by glycolysis is an important alternative, once bis(hydroxiethyl)terephthalate (BHET), high added value monomer, can be obtained. In this context, this study approaches the use of titanate nanotubes (i.e. sodium/protonated titanate nanotubes) as catalyst for PET glycolysis. Reactional conditions, the origin and granulometry of PET flakes were evaluated (at 196 °C). Best results (BHET yield > 80%) were obtained for both catalyst in 3 h of reaction. The protonated titanate nanotubes catalyst were more efficient than sodium titanate nanotubes due to greater concentration of Brönsted and Lewis acid sites, indicated by TPD analyzes.

[Background]: Maintenance therapy following autologous stem cell transplantation (ASCT) can delay disease progression and prolong survival in patients with multiple myeloma. Ixazomib is ideally suited for maintenance therapy given its convenient once-weekly oral dosing and low toxicity profile. In this study, we aimed to determine the safety and efficacy of ixazomib as maintenance therapy following ASCT. [Methods]: The phase 3, double-blind, placebo-controlled TOURMALINE-MM3 study took place in 167 clinical or hospital sites in 30 countries in Europe, the Middle East, Africa, Asia, and North and South America. Eligible participants were adults with a confirmed diagnosis of symptomatic multiple myeloma according to International Myeloma Working Group criteria who had achieved at least a partial response after undergoing standard-of-care induction therapy followed by high-dose melphalan (200 mg/m²) conditioning and single ASCT within 12 months of diagnosis. Patients were randomly assigned in a 3:2 ratio to oral ixazomib or matching placebo on days 1, 8, and 15 in 28-day cycles for 2 years following induction, high-dose therapy, and transplantation. The initial 3 mg dose was increased to 4 mg from cycle 5 if tolerated during cycles 1–4. Randomisation was stratified by induction regimen, pre-induction disease stage, and response post-transplantation. The primary endpoint was progression-free survival (PFS) by intention-to-treat analysis. Safety was assessed in all patients who received at least one dose of ixazomib or placebo, according to treatment actually received. This trial is registered with ClinicalTrials.gov, number NCT02181413, and follow-up is ongoing. [Findings]: Between July 31, 2014, and March 14, 2016, 656 patients were enrolled and randomly assigned to receive ixazomib maintenance therapy (n=395) or placebo (n=261). With a median follow-up of 31 months (IQR 27·3–35·7), we observed a 28% reduction in the risk of progression or death with ixazomib versus placebo (median PFS 26·5 months [95% CI 23·7–33·8] vs 21·3 months [18·0–24·7]; hazard ratio 0·72, 95% CI 0·58–0·89; p=0·0023). No increase in second malignancies was noted with ixazomib therapy (12 [3%] patients) compared with placebo (eight [3%] patients) at the time of this analysis. 108 (27%) of 394 patients in the ixazomib group and 51 (20%) of 259 patients in the placebo group experienced serious adverse events. During the treatment period, one patient died in the ixazomib group and none died in the placebo group. [Interpretation]: Ixazomib maintenance prolongs PFS and represents an additional option for post-transplant maintenance therapy in patients with newly diagnosed multiple myeloma, This study was sponsored by Millennium Pharmaceuticals, a wholly owned subsidiary of Takeda Pharmaceutical Company.

Circadian rhythm synchronizes each body function with the environment and regulates physiology. Disruption of normal circadian rhythm alters organismal physiology and increases disease risk. Recent epidemiological data and studies in model organisms have shown that maternal circadian disruption is important for offspring health and adult phenotypes. Less is known about the role of paternal circadian rhythm for offspring health. Here, we disrupted circadian rhythm in male mice by night-restricted feeding and showed that paternal circadian disruption at conception is important for offspring feeding behavior, metabolic health, and oscillatory transcription. Mechanistically, our data suggest that the effect of paternal circadian disruption is not transferred to the offspring via the germ cells but initiated by corticosterone-based parental communication at conception and programmed during in utero development through a state of fetal growth restriction. These findings indicate paternal circadian health at conception as a newly identified determinant of offspring phenotypes. CA Extern

Summary Broadly neutralizing antibodies (bNAbs) represent a promising approach to prevent and treat HIV-1 infection. However, viral escape through mutation of the HIV-1 envelope glycoprotein (Env) limits clinical applications. Here we describe 1-18, a new VH1-46-encoded CD4 binding site (CD4bs) bNAb with outstanding breadth (97%) and potency (GeoMean IC50 = 0.048 μg/mL). Notably, 1-18 is not susceptible to typical CD4bs escape mutations and effectively overcomes HIV-1 resistance to other CD4bs bNAbs. Moreover, mutational antigenic profiling uncovered restricted pathways of HIV-1 escape. Of most promise for therapeutic use, even 1-18 alone fully suppressed viremia in HIV-1-infected humanized mice without selecting for resistant viral variants. A 2.5-Å cryo-EM structure of a 1-18-BG505SOSIP.664 Env complex revealed that these characteristics are likely facilitated by a heavy-chain insertion and increased inter-protomer contacts. The ability of 1-18 to effectively restrict HIV-1 escape pathways provides a new option to successfully prevent and treat HIV-1 infection., Graphical Abstract, Highlights • Identification of 1-18, a highly broad and potent VH1-46-derived CD4bs antibody • 2.5-Å cryo-EM structure of 1-18-Env complex reveals inter-protomer contacts • 1-18 overcomes VRC01-class resistance and restricts development of HIV-1 escape • Monotherapy with 1-18 maintains viral suppression in HIV-1YU2-infected humanized mice, Broadly neutralizing antibodies targeting the HIV-1 envelope protein are a promising option for prevention and treatment of HIV-1 infection. However, development of viral resistance can limit clinical efficacy. Schommers et al. identify a highly broad and potent antibody that targets the CD4 binding site of HIV-1. Compared with other potent CD4 binding site antibodies, it restricts the development of viral escape and effectively suppresses HIV-1 in vivo.

In this study, a novel and straightforward analytical methodology was proposed for the determination of cocaine (COC) and its main metabolites benzoylecgonine (BZE) cocaethylene (CE) and hydroxy‑cocaine (COC OH) in urine samples. This approach consisted of a high-throughput and semiautomated configuration based on hollow-fiber renewal liquid membrane extraction (HFRLM) coupled to a 96-well plate system, which was proposed for the first time to analyze complex biological samples such as urine. The analytical determinations were performed using ultra-high performance liquid chromatography coupled to quadrupole time-of-flight-mass spectrometry (LC–ESI–QTOF–MS). The analytical methodology was fully optimized through Doehlert and simplex-centroid designs, and univariate approaches. Polypropylene membranes of 1 cm length were inserted in the pins of an extraction blade combined with a 96-well plate system and its pores were filled with hexane:dichloromethane:ethyl acetate (1:1:1 v/v/v) for 180 s; moreover, 20 µL of this mixture was added to the sample to allow for a renewable liquid membrane. The extraction step was carried out by keeping the blades immersed in vials containing 1.5 mL of diluted urine adjusted at pH 10 with 10% (w/v) of Na2CO3 during 20 min, followed by liquid desorption with 100 µL of acetonitrile. Finally, the extract was dried under N2 stream and resuspended with 20 µL of ultrapure water. Satisfactory analytical performance was obtained with coefficients of determination ranging from 0.9875 for BZE to 0.9986 for CE; intra-day precision ranged from 1.6 to 13.5%, and inter-day precision varied from 2.2 to 17.5%. Limits of detection ranged from 1.5 to 15.1 ng mL−1, and limits of quantification varied from 5 to 50 ng mL−1, with relative recoveries varied from 70.7 to 124.1%.

p38 and Akt plays an important role in neuropathic pain. p38 appears to regulate the SVCT-2 expression, a specific transporter for ascorbic acid (an important antioxidant and neuromodulator). Vitamins C and E induce antinociception and appear to affect p38, Akt, and SVCT-2, but it is unknown their effect on these molecules in spinal cord of rats with chronic constriction injury (CCI) of the sciatic nerve, a model of neuropathic pain. So, we investigated the effect of vitamins C + E on the expression of p38, Akt, and transporter SVCT-2 and ascorbic acid content in the lumbosacral spinal cord of rats with CCI. TNF-α mRNA level was also determined. Placement of four loose chromic thread ligatures around the sciatic nerve produced CCI. Ascorbic acid (vitamin C 30 mg/kg/day) + α-tocopherol (vitamin E 15 mg/kg/day) or vehicle (saline containing 1% Tween 80) were administrated (intraperitoneally) daily after CCI for 3 or 10 days. At the end of these periods, lumbosacral spinal cord was dissected out and used for assays. The vitamins prevented the increase in phosphorylated p38 and phosphorylated Akt and the decrease in SVCT-2 expressions, which were found in vehicle-treated CCI rats at days 3 and 10. Akt expression was reduced only at day 10. Vitamins also prevented the increase in ascorbic acid content and TNF-α level, which was found in vehicle-treated CCI rats. The changes in p-p38, p-Akt, ascorbic acid, SVCT-2, and TNF-α may be contributing to antinociception induced by vitamins C + E in rats with CCI.

Introduction Ayahuasca is a beverage composed by a mixture of herbs which contain the compound N,N-dimethyltriptamine (DMT) and the β-carbolines. Although its use is legalized in Brazil only for religious and spiritual ceremonies, there is a growing black market specialized in the distribution of these compounds in form of herbal material through internet and mail. The purpose of this work was the development of an ultra-high-performance liquid chromatography-tandem mass spectrometry method for the determination of ayahuasca alkaloids and its application in seized ayahuasca products. Methods An aliquot of seized products was weighted and diluted with methanol. An aliquot of this solution was added with internal standard (DMT-d6), followed by injection in the analytical system. Results The limit of quantitation was 10 ng/mL for DMT and 25 ng/mL for harmine, harmaline and tetrahydroharmine. The concentration ranges used were 10–100 ng/mL for DMT, harmine and harmaline and all analytes presented a coefficient of determination (r2) ≥ 0,99. Analysis of four seized samples presented concentrations of DMT ranging between 31.5 and 46.5 mg/g. Presence of β-carbolines was not detected in the products. The variability of DMT concentrations can be correlated with the potential intoxications described in the literature. Conclusion This work successfully established a determination method for ayahuasca alkaloids in herbal material. In addition, the workflow proved to be simple, rapid and useful to estimate the concentration of psychoactive compounds in seized materials, leading to further investigation of ayahuasca ritualistic or recreational exposure.

The application of fluorescent tags to generate cell type-specific translational and transcriptional reporter lines is routine in plants, but separation of different cell types for downstream analyses is hampered by the presence of cell walls and tight connections between cells. Enzymatic removal of cell walls induces a wound response, dedifferentiation, or reprogramming of the resulting protoplasts. Their osmotic and mechanical instability and their large size range are challenging for FACS, a flow -sorting procedure based on differential expression of fluorescent tags. In contrast, plant nuclei are relatively robust and easy to isolate. Here, we describe a protocol for fluorescence-activated nuclear sorting (FANS) that allows efficient purification of very few fluorescence-tagged nuclei from a large background of non-labeled tissue. Purified nuclei are suitable for genome, epigenome, transcriptome, or proteome analyses. We describe in detail how to analyze nuclear RNA and DNA methylation from sorted nuclei representing the limited number of stem cells in the shoot apical meristem of Arabidopsis.

Flexible risers are critical equipment for the production of oil and gas in offshore fields around the world. The annulus region may condense acidic water containing H2S exposing the tensile armour steel wires to a sour environment, which may promote sulphide stress cracking (SSC) and/or hydrogen-induced cracking (HIC). This work aims to evaluate through electrochemical and constant displacement tests the effectiveness of thermal spray aluminium (TSA) coating to mitigate SSC and HIC in high strength steel used to manufacture the tensile armour of a flexible riser. Electrochemical tests confirmed the anodic behaviour of the coating against the steel and estimated a service life of 2.5 years. The constant displacement test indicated that the non-coated samples failed by SSC although some cracks were also found in the samples mid-section due to HIC. For Al-coated samples, no signs of SSC and HIC were observed. The TSA coating showed a dual barrier effect, hindering either corrosion of steel or hydrogen up-taking, and neither SSC nor HIC was observed. Samples with a coating defect were cathodically protected and no HIC was observed.

International audience; Aluminium oxide (Al 2 O 3) films were deposited on silicon substrates using plasma-enhanced atomic layer de-position (PE-ALD) technique with tri-methyl-aluminium TMA (Al(CH 3) 3) and dioxygen (O 2) as precursors. PE-ALD experiments were performed in order to (i) investigate the interfacial properties between the silicon sub-strate and the alumina layer, and (ii) understand the impact of growth and crystallization phenomena on the Al 2 O 3 films properties (structural, optical, mechanical, dielectric and etch). The formation of oxide-based transition layers, either silicon oxide SiO 2 and/or aluminosilicate Al x Si y O, was evidenced for the TMA/O 2 PE-ALD process. Based on these results, it appears that no substrate-enhanced growth occurs at the early stages of the growth process, as assumed in previous reports. Thus, constant growth rate (0.08 nm per cycle) and re-fractive index (1.64 at a 450 nm wavelength) were obtained for the Al 2 O 3 layer deposited at 300 °C. Finally, thermal annealing experiments were performed on these films, evidencing the influences of atomic structural rearrangement and crystallization on the Al 2 O 3 film main characteristics: interface steepness, atomic structure, refractive index, residual stress, dielectric constant and etch rate.

O zinco é um elemento essencial às plantas, mas quando presente em altas concentrações no solo pode se tornar tóxico ao metabolismo vegetal. O trabalho objetivou determinar o crescimento e tolerância de mudas de Enterolobium contortisiliquum Vell. cultivadas em solo contaminado com zinco. O experimento foi conduzido em casa de vegetação, em solo com 81% de argila, no delineamento inteiramente casualizado, com sete tratamentos, constituídos de doses de zinco (0, 100, 200, 300, 400, 500 e 600 mg kg-1) e oito repetições. Avaliou-se a altura de planta, diâmetro de colo, massa seca aérea, massa seca radicular, comprimento da raiz principal, área superficial específica, teor de Zn na parte aérea e radicular, coeficiente do impacto do teor relativo de zinco, índice de translocação e de tolerância. O coeficiente do impacto do teor relativo de zinco indicou tendência de menor translocação de Zn à parte aérea da muda até a dose de 300 mg de Zn kg-1 de solo. Os resultados evidenciaram que doses próximas a 200 mg de zinco kg-1 de solo argiloso estimulam a altura de planta, diâmetro do colo, a massa seca aérea e radicular das mudas de timbaúva. A timbaúva apresenta elevada tolerância ao zinco e por ser uma arbórea nativa adaptada às condições ambientais do Brasil pode ser indicada para revegetação de áreas contaminadas com a aplicação de até 600 mg de zinco kg-1 de solo argiloso.

The functions of drilling fluids depend directly on the fluid’s physical, chemical, and rheological properties. The selection and control of fluid composition is crucial to obtain the best performance in the process of drilling oil. The presence of solid particulate material and viscosifying agents contributes to the maintenance of the rheological behavior of these fluids. The pH variation during the drilling may affect rheological properties leading to poor well cleaning and drill string imprisonment. This work aims to evaluate the influence of solid concentration and pH variation in the rheological behavior of carboxymethyl cellulose and natural clay dispersions. Results indicated that solid concentration increased the apparent viscosity of dispersions due to chemical interactions between the polymer and the particles of natural clay. Dispersions at a pH lower than five presented lower values of yield stress and apparent viscosity than dispersions with higher pH values. The protonation of the carboxylic groups of the NaCMC resulted in a hydrophobicity increase of NaCMC and in a subsequent reduction of natural clay wettability. The formation of natural clay aggregates caused a decrease in dispersion viscosity.

In this paper, the results of a pilot study on the profiling of the synthetic cannabinoid receptor agonist 5F-PB-22 (5F-QUPIC, pentylfluoro-1H-indole-3-carboxylic acid-8-quinolinyl ester) via isotope ratio mass spectrometry are presented. It focuses on δ13 C, δ15 N and δ2 H isotope ratios, which are determined using elemental analyser (EA) and high temperature elemental analyser (TC/EA) coupled to an isotope ratio mass spectrometer (IRMS). By means of a sample of pure material of 5F-PB-22, it is shown that the extraction of 5F-PB-22 from herbal material, a rapid clean-up procedure, or preparative column chromatography had no influence on the isotope ratios. Furthermore, 5F-PB-22 was extracted from 14 different herbal blend samples ("Spice products" from police seizures) and analysed via IRMS, yielding 3 clusters containing 7, 5, and 2 samples, distinguishable through their isotopic composition, respectively. It is assumed that herbal blends in each cluster have been manufactured from individual batches of 5F-PB-22.

We report on the optimisation of precursor gas composition for the repeatable preparation of large area highly conductive boron doped nano-crystalline diamond layers with low sp 2 content using microwave plasma enhanced linear antenna chemical vapour deposition apparatus. The precursor gas composition parameter space was probed by varying the boron, oxygen and carbon atomic ratios whilst fixing all other parameters constant. By radically increasing the B content and careful consideration of the B and O content in the gas phase, thin B-NCD layers (∼300 nm) were prepared over large areas, repeatable, with high boron concentrations (∼2 × 10 21 at/cm 3 ) and electrical conductivity levels akin to B-NCD layers prepared in conventional MW PECVD systems (>35 S cm −1 ) with electrochemical properties suitable for industrial applications.

Introduction The presence of anabolic-androgenic steroids (AAS) in illegal commercial products has been pointed as a global threat for public health. Due the correlation with adverse toxicological effects, there is a growing interest in the implementation of straightforward methods for the determination of AAS in seized products. This work exploited the development of a mass spectrometry approach to characterize the illegal oil formulations containing AAS. Methods The optimization of sample preparation was performed through a simplex-centroid design and the best condition was described as follow: an aliquot of 5 μL of sample were added with 995 μL of acetonitrile and water (75:25, v/v). The solution was vortexed and centrifuged. After that, 10 μL of supernatant were added with 35 μL of acetonitrile and water and internal standard (testosterone-d3, 1.25 ng). An aliquot of 5 μL was injected into the analytical system. Results The method developed was validated and successfully applied in 115 seized samples. Testosterone and its esters had the highest incidence, found in more than 50% of the samples. Besides that, drugs such as boldenone, methandienone, and trenbolone have also been found, where the low quality of the samples was evidenced by the wide variation in the concentration of the drugs, always quantified in sub-doses. Finally, at least one AAS was detected in each sample analyzed. The statistical results were grouped by principal components analysis, to better understand the profile of the seized samples. Conclusion This work successfully established a fast and simple method for determination of AAS and can be applied to verify the profile of seized samples.

Super duplex stainless steels (SDSS) have emerged in the last decade or so as a candidate material to withstand harsh oil and gas production environments. However, documented cases of failure due to hydrogen induced stress cracking (HISC) have raised some concerns. The aim of this investigation is to evaluate the effect of the cathodic protection potential and K-rate on the susceptibility of SDSS to HISC. The results indicated that although the susceptibility to HISC might appear unequivocal, the tests parameters should be carefully considered since they influence dramatically on the results produced. Indeed, for more cathodic electrode potentials stronger is the detrimental effect on fracture toughness while the influence of K-rate is rather weak. However, the influence of this latter parameter becomes more relevant when the applied electrode potential is less negative.

The main objective of this work was to study the dissolution of salt (NaCl) particles in water and in non-Newtonian fluids that contain xanthan gum. In an agitated tank, experimental profiles of salt concentration as a function of time in the liquid phase were obtained. The experimental data were used to evaluate the mass transfer coefficient in different operational conditions and to validate the mathematical model. It was found that the dissolution kinetics of the salt particles was affected by both the fluid's xanthan gum concentration and initial salt concentration. Adding xanthan gum to the fluid decreased the salt dissolution kinetics. The mass transfer coefficient for a system with xanthan gum was smaller than the one for pure water. The values of the mass transfer coefficient for pure water base fluids varied from (0.836 ± 0.003) × 10−4 to (1.110 ± 0.003) × 10−4 m/s, and for xanthan gum solutions from (0.526 ± 0.003) × 10−4 to (0.865 ± 0.003) × 10−4 m/s. The mathematical model based on the mass conservation equations for the liquid and solid phases predicts the salt concentration profiles simulating the dissolution process. In addition, it was proposed an equation to model the decrease in the diameter of the particles due to dissolution. The mathematical model fitted the experimental data with an average relative error of 2.2%.

The molecular design of smart polymer surfaces and control over functionality in a way that the properties can be changed by external triggers garnered a great deal of attention of polymer chemists in the last decade. Here, we introduce the formation of a dual-responsive, i.e. reduction- and oxidation-responsive, cobalt-containing polymer core-shell particle system, displaying a reversibly switchable behavior by means of chemical oxidation reagents as well as electrochemistry experiments. The responsiveness is based on a cobalt(I)-containing shell material, which is obtained by a surface-initiated atom transfer radical polymerization (SI-ATRP) protocol for (η 5 -cyclopentadienyl-4-hydroxybutan-1-on)cobalt(η 4 -tetraphenyl-cyclobutadiene) methacrylate (CpCoCbMA). The novel metallopolymer particles featuring a cobalt-containing shell are investigated by transmission electron microscopy (TEM), scanning electron microscopy (SEM) with energy dispersive X-ray spectroscopy (EDX), while control over the ATRP approach is shown by characterizing freely formed poly(CpCoCbMA) chains by size-exclusion chromatography (SEC). The responsive behavior of the poly(CpCoCbMA)-containing shell is investigated by dynamic light scattering (DLS) and cyclic voltammetry (CV) measurements indicating a tremendous change of the particle hydrodynamic radii and dispersion capability in organic polar and non-polar solvents. Transformation of these preceramic cobalt-grafted core-shell particles to cobalt oxide-based materials is investigated after convenient thermal treatment. Overall, the herein reported redox-mediated core-shell cobalt-containing polymer architectures open a variety of applications for switchable and electrochemical devices.

This work presents the modeling of a vertical falling film expanding or shrinking from the inlet manifold. Considering a stationary approach, the film shape, the flow field and the absorption rate of an ambient gas are computed. For the flow field, one dimensional (1-D) second-order weighted integral boundary layer (WIBL) model is shown to accurately reproduce the film deformations. The gas transfer is then solved in a 2-D predeformed domain to investigate the impact of the film deformations on the gas absorption rate. It is found that a significant mass transfer enhancement, as compared to a flat film, is obtained when the film is expanding due to the concomitant increase of the concentration gradient perpendicular to the interface. On the contrary, a slight hindrance of the mass transfer is observed when the film is shrinking, although it remains in this case very close to the flat film analytical solution. © 2017 American Institute of Chemical Engineers AIChE J, 63: 4370–4378, 2017

The synthesis and characterization of a lipidlike electrostatic spin probe, (S)-2,3-bis(palmitoyloxy)propyl 2-((4-(4-(dimethylamino)-2-ethyl-1-oxyl-5,5-dimethyl-2,5-dihydro-1H-imidazol-2-yl)benzyl)disulfanyl)ethyl phosphate (IKMTSL-PTE), are being reported. The intrinsic pKa0 of IKMTSL-PTE was determined by X-band (9.5 GHz) electron paramagnetic resonance (EPR) titration of a water-soluble model compound, 4-(dimethylamino)-2-ethyl-2-(4-(((2-hydroxyethyl)disulfanyl)methyl)phenyl)-5,5-dimethyl-2,5-dihydro-1H-imidazol-1-oxyl (IKMTSL-ME), an adduct of methanethiosulfonate spin label IKMTSL and 2-mercaptoethanol. The pKa0 of IKMTSL-ME in bulk aqueous solutions was found to be significantly higher than that of 4-(((2-hydroxyethyl)disulfanyl)methyl)-2,2,3,5,5-pentamethylimidazolidin-1-oxyl (IMTSL-ME), an adduct of the corresponding methanethiosulfonate spin label IMTSL and 2-mercaptoethanol (17 °C, pKa0 = 6.16 ± 0.03 vs 20 °C, pKa0 = 3.33 ± 0.03, respectively). A series of EPR titration experiments with IKMTSL-ME in aqueous solutions containing 0-60% v/v isopropanol have been carried out at 17 and 48 °C to determine the effects of temperature and bulk dielectric permittivity constant, e, on the probe pKa. A linear relationship between the probe pKa and e has been established and found to be essentially the same at 17 and 48 °C. The polarity term contributing to the pKa of IKMTSL-PTE at an uncharged lipidlike interface was determined by incorporating the probe into electrically neutral micelles formed from nonionic detergent Triton X-100, and it was found, similar to IMTSL-PTE, to be negative. In negatively charged DMPG lipid bilayers, IKMTSL-PTE exhibits ionization transitions with significantly higher pKa values than those previously reported for IMTSL-PTE (e.g., at 17 °C, pKai = 7.80 ± 0.03 vs pKa0 = 5.70 ± 0.05). The surface electrostatic potentials of DMPG lipid bilayers calculated using IKMTSL-PTE titration data were found to be somewhat lower than those calculated using IMTSL-PTE. The lower values measured by IKMTSL-PTE are the likely consequences of the structure of the linker that positions the reporter nitroxide further away from the bilayer plane into aqueous phase. Overall, the ionization transitions of IKMTSL-PTE with pKa values close to the neutral pH range make this lipidlike molecule a valuable spectroscopic EPR probe for studying the electrostatic phenomena at biological interfaces, including lipid bilayer/membrane protein systems, that could be unstable in the acidic pH range accessible by the previously available probes.

Soil contamination with zinc occurs in mining and agricultural areas through successive applications of pig slurry. Essential to the selection and adaptation of plants to contaminated soil, is the study of species showing not only tolerance but also bioaccumulation or bioconcentration of zinc associated with amelioration. In this context, this study aimed to evaluate the influence of peat addition on the tolerance, bioconcentration and bioaccumulation of Zn in Eucalyptus grandis seedlings. A completely randomized experimental design was used, in a factorial arrangement (2 x 6), with and without the addition of peat (200 mL L-1 soil) and six doses of Zn (zero, 200, 400, 600, 800 and 1000 mg kg-1) with 15 replications, conducted for 120 days. The height, stem diameter, root and shoot dry weight, concentration and Zn content in the root system and aerial parts, indices of tolerance and translocation, and bioaccumulation factors and bioconcentration were evaluated. The addition of 200 mL L-1 of peat provided increased tolerance and a stimulating effect on morphological parameters of E. grandis seedlings. This species, however, did not concentrate zinc to the extent that it could be considered a bioaccumulating plant. Key words: Contaminated soil, phytoremediation, zinc contamination, amelioration.

Introduction: The treatment of patients (pts) with rrMM remains challenging and response is often limited in depth and duration. In contrast to many other malignant diseases, targeted therapy in MM is hampered by the limited number of actionable targets. Activating mutations of BRAF have been found in 2-4% of newly diagnosed MM and in up to 8% of rrMM. Several case reports have reported clinical efficacy of downstream pathway inhibition in MM. This phase II trial is evaluating the safety and efficacy of combined BRAF/MEK inhibition in rrMM pts with BRAF V600E mutation. Aims: The primary objective of this study was to demonstrate the therapeutic efficacy of encorafenib in combination with binimetinib. The primary endpoint was the overall response rate (ORR), defined as best response within 1 year of treatment. Main secondary endpoints included progression-free survival (PFS) and duration of response. Safety analyses included all adverse events (AEs) with those of grade 1/2 only being assessed further if considered to be related to study medications by the investigator. Methods: A total of 15 pts with rrMM who have failed at least 2 prior lines of therapy, including a proteasome inhibitor (PI) and an immunomodulatory drug (IMID), were planned to be enrolled in this open-label phase II multicenter trial. Key inclusion criteria were presence of a BRAF V600E/K mutation confirmed by both mutation-specific immunohistochemistry (IHC) and next-generation sequencing in more than 50% of MM cells. Exclusion criteria included plasma cell leukemia, CNS involvement, cardiac dysfunction, or a history of retinal vein occlusion. Pts received encorafenib 450mg p.o. daily and binimetinib 45mg p.o. twice daily. Responses were assessed using IMWG 2016 criteria. The primary endpoint was analyzed by testing the one-sided null hypothesis of ORR Results: As of July 2020, 12 pts have been enrolled and were evaluable for safety and 11 pts were evaluable for response as 1 pt had just completed cycle 1 with confirmation of response pending at the time of data lock. Subtypes of MM were IgG in 6 pts, IgA in 2 pts, and Bence Jones in 4 pts. Pts had received a median of 5 prior lines of therapy (range 2-14). All pts had failed previous treatment with both a PI and an IMID and in addition carfilzomib, pomalidomid, and/or anti-CD38 antibodies in 8/4/6 pts, respectively. The study already reached its primary endpoint. The ORR was 82% (lower limit of the 95% CI 56.4%, one-sided exact binomial test, p Adverse events of all grades, assessed to be at least possibly related to a study drug, occurred in 9/12 pts and included blurred vision, macula edema, cramps, arthralgia, diarrhea, skin rash, and decreased left ventricular function. Grade 3 or 4 AEs irrespective of causality occurring in more than 1 pt were reported in 8 pts with anemia, hypertension and thrombocytopenia (3/ 3/ 2 pts, respectively). SAEs were reported in 2 pts, respiratory tract infection in both pts and tooth decay in 1 pt that was not related to the study medication. No deaths occurred while on treatment or within 30 days of the end of treatment. Preliminary results of biomarker assessments reveal new RAS mutations and amplification of the BRAF locus at the time of relapse while on study treatment as potential markers of resistance. Analysis of pharmacodynamic markers by phospho-IHC reveals suppression of BRAF/MEK signaling at cycle 1 / day 28 and restoration of expression at the time of relapse. Conclusion: Targeting activating BRAF mutations in rrMM by combining the BRAF inhibitor, encorafenib, and the MEK inhibitor, binimetinib, induces rapid and deep responses in the majority of pts. No new safety signal has been observed when compared to prior reports on these compounds. The study reached its primary endpoint with fewer pts than expected. The primary efficacy and safety analysis will be presented at the conference. Disclosures Raab: Janssen: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Heidelberg Pharma: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees. Scheid:BMS: Honoraria; Amgen: Honoraria; Novartis: Honoraria, Research Funding; Takeda: Honoraria, Research Funding; Janssen: Honoraria, Research Funding. Besemer:GSK: Honoraria; Janssen: Honoraria. Metzler:Janssen: Consultancy; Amgen: Consultancy; Takeda: Consultancy; GSK: Consultancy; BMS: Consultancy. Khandanpour:Astra Zeneca: Research Funding; Sanofi: Consultancy; Janssen: Consultancy; Amgen: Consultancy; Celgene: Consultancy. Trautmann-Grill:Janssen: Consultancy; Celgene: Consultancy; Sanofi: Consultancy; Takeda: Consultancy, Honoraria; GSK: Consultancy; BMS: Honoraria. Goldschmidt:Mundipharma GmbH: Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck Sharp and Dohme (MSD): Research Funding; Chugai: Honoraria, Other: Grants and/or provision of Investigational Medicinal Product:, Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Grants and/or provision of Investigational Medicinal Product:, Research Funding; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Grants and/or provision of Investigational Medicinal Product:, Research Funding; University Hospital Heidelberg, Internal Medicine V and National Center for Tumor Diseases (NCT), Heidelberg, Germany: Current Employment; GlaxoSmithKline (GSK): Honoraria; Adaptive Biotechnology: Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Grants and/or provision of Investigational Medicinal Product, Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Grants and/or provision of Investigational Medicinal Product:, Research Funding; Novartis: Honoraria, Research Funding; Molecular Partners: Research Funding; Incyte: Research Funding; Johns Hopkins University: Other: Grants and/or provision of Investigational Medicinal Product; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other, Research Funding; Dietmar-Hopp-Foundation: Other: Grants and/or provision of Investigational Medicinal Product:. Weisel:Abbvie: Consultancy, Honoraria; Adaptive: Consultancy, Honoraria; GlaxoSmithKline: Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Roche: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Karyopharm: Consultancy, Honoraria; Takeda: Consultancy, Honoraria. OffLabel Disclosure: Encorafenib and Binimetinib in BRAF V600E mutant multiple myeloma

Background: Perioperative damage of neuronal tissue due to insufficient cerebral circulation as a result of hypotension or stroke, lead to permanent destruction and functional impairment via apoptotic and inflammatory pathways. Recently, the noble gas argon has been shown to exert neuroprotective effects. Despite intensive research, the exact mechanism remains unclear. Methods: In-vitro, after injury of human neuroblastoma cells with rotenone over a period of four hours, postconditioning with argon 75 Vol% was performed for 2. In-vivo, retinal ischemia reperfusion injury in the rat was induced by increasing intraocular pressure for 1 hour (h). Upon reperfusion, argon was administered by inhalation for 2 h. Results: In summary, argon reduced binding activity of transcription factors involved in regulation of neuronal damage such as STAT3 (Signal transducer and activator of transcription 3), NF-kB (Nuclear factor `kappa-light-chain-enhancer´ of activated B-cells), AP-1 (Activator protein 1) and Nrf-2 (Nuclear factor erythroid 2-related factor 2). Flow cytometry analysis showed that argon down-regulated the Fas-Ligand. Since some of these transcription factors were regulated via toll-like receptors (TLR), their effects could be eliminated - at least in part - by OxPAPC (TLR2 and -4 inhibitor). Argon was able to reduce the quantity and the activity of neuronal microglia after ischemia-reperfusion injury. Consecutively, qPCR (quantitative Polymerase chain reaction) showed a reduction of the pro-inflammatory cytokines IL-1α (Interleukin-1α), IL-1ß (Interleukin-1ß), IL-6 (Interleukin 6), TNFα (Tumor necrosis factor alpha) and iNOS (inducible Nitric oxide synthase). Conclusion: Argon reduced the extent of inflammation after neuronal injury by suppression of transcription factors crucial for microglia activation. The therapeutic use of the noble gas would be ideal for treating in the context of neuronal damage due to the lack of known side effects and narcotic properties with preservation of neurological assessability. Although preclinical studies are promising, further investigations are required before argon can be approved for use in patients.

International audience; During the first stages of Atomic Layer Deposition (ALD) of Al 2 O 3 on silicon (Si), the substrate nature affects the surface chemistry, leading to an initial island growth mode. Furthermore, an interfacial zone develops between the Si surface and the dielectric, thus damaging the physical properties of the deposited structure. In this work, these two main shortcomings are investigated for the ALD of Al 2 O 3 films on Si from TMA and H 2 O. The film and the interfacial zone are characterized by a complete range of techniques, including XRR, TEM, XPS, EDX and ToF-SIMS. In parallel, a computational model is developed to study the initial nucleation and growth steps of the film. An induction period is experimentally evidenced and numerically reproduced, together with the island growth and coalescence phenomena. The chemical composition of the (Al, O, Si) interfacial layer is precisely analyzed to get insight in the mechanisms of its formation. We show that Si oxidation occurs during the island growth, catalyzed by the presence of Al, while it is also fed by species interdiffusion through the ALD film.

International audience; The initial substrate inhibiting island growth and the formation of an interfacial layer with uncontrollable characteristics are the two main drawbacks of the Atomic Layer Deposition (ALD) of high-k metal-oxide gate dielectrics on silicon (Si). In this paper, we investigate the ALD of Al2O3 films from trimethyl aluminum and H2O, on fluorhydric acid (HF) cleaned, as well as on HF-cleaned and in situ N2-NH3 plasma pretreated Si between 0 and 75 cycles. The films and their interface were characterized via Scanning Transmission Electron Microscopy coupled to Energy-Dispersive X-ray spectroscopy. The initial deposition is clearly increased on the pretreated surfaces, obtaining a linear ALD regime even after 5 ALD cycles, compared to several tens of cycles needed on HF-cleaned Si. Furthermore, a SixNy layer is formed by the N2-NH3 plasma pretreatment, which acts as a barrier layer, reducing the oxidation of the Si substrate beneath it. This analysis provides a general framework for the understanding and determination of adequate surface pretreatments, able to combat the substrate inhibited initial growth and the Si oxidation during metal-oxide ALD on Si.ACKNOWLEDGMENTS

Particle production at LHC energies involves the interplay of hard (perturbative) and soft (non-perturbative) QCD processes. Global observables, such as the charged-particle multiplicity, are related to the initial geometry and the energy density produced in the collision. They are important to characterise relativistic heavy-ion collisions and to constrain model calculations. The LHC produced Xenon-Xenon collisions for the first time in October 2017. New results on the primary charged-particle pseudorapidity density, and its pseudorapidity and centrality dependence are presented for this lighter and deformed nucleus, and compared to measurements obtained for lead ions. New results will also be presented for p-Pb collisions at the highest energy of 8.16 TeV, as part of an overview of all the measurements at LHC Run 1 and 2 energies. These studies allow us to investigate the evolution of particle production with energy and system size and to compare models based on various particle production mechanisms and different initial conditions., Comment: 4 pages, 5 figures

Nitrocarburizing is considered one of the most important thermochemical treatments for surface modification of metallic materials and involves the simultaneous diffusion of nitrogen and carbon onto the surface. Understanding and controlling the formation of the nitrocarburized layer have considerable industrial interest due to the improvements regarding wear, fatigue, and corrosion resistances. DIN 100Cr6 steel samples were treated by plasma nitrocarburizing for two hours, with two treatment temperatures (550 and 600°C) and four methane concentrations in the gas mixture composition (0, 1.0, 1.5, and 2.0%). SEM and XRD analyses, and wear resistance tests were used to characterize the samples. Results showed that the treatment temperature and atmosphere composition had considerable influence on the compound layer morphology. For nitrided samples the compound layer consists of γ'-Fe4N phase, and the presence of carbon in the gas mixture helps stabilize the ɛ-Fe2-3N phase. Higher CH4 concentration in the treatment atmosphere improve the sample superficial wear resistance.