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[EN] For producing second-generation ethanol (cellulosic ethanol) and other value-added bioproducts, magnetic graphene oxide (GO-MNP) was synthesized in this work and used as the immobilization support for an industrial cellulase-and xylanase-containing preparation. GO-MNP characterization by TEM, SEM and ATR-FTIR spectroscopy showed that the magnetic nanoparticles are homogeneously distributed onto the GO sheets surface. The enzymatic preparation was immobilized by means of carbodiimide cross-linking chemistry using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide and N-hydroxysuccinimide (NHS). The supported final biocatalyst (GO-MNP-Enz) showed high activity for the hydrolysis of pretreated sugarcane bagasse (PSB) and presented relative endoglucanase, xylanase, beta-glucosidase, and beta-xylosidase activities of 70%, 66%, 88%, and 70%, respectively, after 10 cycles of hydrolysis of their respective substrates. The biocatalyst also maintained approximately 50% and 80% of its efficiency for cellulose and xylan hydrolysis, respectively, being the TOF (g.g(-1).h(-1)) the highest observed when compared with previous results reported in literature. These findings suggest that GO-MNP-Enz may be a prospective candidate for industrial applications such as second-generation ethanol production. (C) 2020 Elsevier Ltd. All rights reserved., Sao Paulo State Research Support Foundation (FAPESP) contract number 2018/06241e3 funding this work. Coordination of Improvement of Higher Education Personnel (CAPES) funding the doctoral scholarship of Fernando Roberto Paz-Cedeno in Brazil and in the Universitat Politecnica de Valencia (UPV), Institute of Chemical Technology (ITQ), Valencia, Spain. Authors acknowledge financial support from PGC2018-097277-B-100 (MCIU/AEI/FEDER,UE) project and Severo Ochoa Program (SEV-2016-0683).

The first enantioselective alkylation of 5‐aminopyrazoles is described with good results. The organocatalytic alkylation of 5‐aminopyrazoles have been accomplished using benzoxathiazine 2,2‐dioxides as electrophiles and a bifunctional squaramide organocatalyst.

Noninvasive early indicators of treatment response are crucial to the successful delivery of precision medicine in children with cancer. Neuroblastoma is a common solid tumor of young children that arises from anomalies in neural crest development. Therapeutic approaches aiming to destabilize MYCN protein, such as small-molecule inhibitors of Aurora A and mTOR, are currently being evaluated in early phase clinical trials in children with high-risk MYCN-driven disease, with limited ability to evaluate conventional pharmacodynamic biomarkers of response. T1 mapping is an MRI scan that measures the proton spin-lattice relaxation time T1. Using a multiparametric MRI-pathologic cross-correlative approach and computational pathology methodologies including a machine learning–based algorithm for the automatic detection and classification of neuroblasts, we show here that T1 mapping is sensitive to the rich histopathologic heterogeneity of neuroblastoma in the Th-MYCN transgenic model. Regions with high native T1 corresponded to regions dense in proliferative undifferentiated neuroblasts, whereas regions characterized by low T1 were rich in apoptotic or differentiating neuroblasts. Reductions in tumor-native T1 represented a sensitive biomarker of response to treatment-induced apoptosis with two MYCN-targeted small-molecule inhibitors, Aurora A kinase inhibitor alisertib (MLN8237) and mTOR inhibitor vistusertib (AZD2014). Overall, we demonstrate the potential of T1 mapping, a scan readily available on most clinical MRI scanners, to assess response to therapy and guide clinical trials for children with neuroblastoma. The study reinforces the potential role of MRI-based functional imaging in delivering precision medicine to children with neuroblastoma. Significance: This study shows that MRI-based functional imaging can detect apoptotic responses to MYCN-targeted small-molecule inhibitors in a genetically engineered murine model of MYCN-driven neuroblastoma.

Parvalbumin-expressing (PV+) interneurons play a key role in the maturation and synchronization of cortical circuitry and alterations in these inhibitory neurons, especially in the medial prefrontal cortex (mPFC), have been found in different psychiatric disorders. The formation of perineuronal nets (PNNs) around many of these interneurons at the end of the critical periods reduces their plasticity and sets their connectivity. Consequently, the presence of PNNs must have an important impact on the synaptic input and the physiology of PV+ cells. In the present study, we have found that in adult male mice, prefrontocortical PV+ cells surrounded by PNNs show higher density of perisomatic excitatory and inhibitory puncta, longer axonal initial segments (AISs), and higher PV expression when compared with PV+ cells lacking PNNs. In order to better understand the impact of PNNs on the connectivity and physiology of PV+ interneurons in the mPFC, we have digested enzymatically these structures and have found a decrease in the density of inhibitory puncta on their perisomatic region but not on the PV+ perisomatic puncta on pyramidal neurons. Moreover, extracellular recordings show that the digestion of PNNs induces a decrease in γ activity, an oscillation dependent on PV+ cells, in the mPFC of anesthetized mice. Our results suggest that the presence of PNNs enwrapping PV+ cells regulates their inhibitory input and has a potent influence on their activity. These results may be relevant for psychiatric research, given the alterations in PNNs, PV+ interneurons and their physiology described in different mental disorders. SIGNIFICANCE STATEMENT Parvalbumin-expressing (PV+) interneurons are surrounded by specializations of the extracellular matrix, the perineuronal nets (PNNs). PNNs regulate the development and plasticity of PV+ cells and, consequently, their presence must influence their synaptic input and physiology. We have found, in the adult prefrontal cortex (PFC), substantial differences in the structure and connectivity of PV+ interneurons depending on the presence of PNNs. The depletion of PNNs from the PFC has also a potent effect on the connectivity of PV+ cells and on neural oscillations that depend on these cells. These findings are relevant to understand the role of PNNs in the adult brain and in certain psychiatric disorders in which alterations in PNNs and PV+ interneurons have been described.

Herein, an efficient asymmetric aminoalkylation of pyrazolones with α-amido sulfones catalyzed by a quinine-derived squaramide in dichloromethane/aqueous media has been established. A variety of chiral amines were obtained with high yields (up to 98%) and excellent enantioselectivities (up to 99% ee). The corresponding products are transformed into optically active acetylated pyrazoles after treatment with Ac2O/Et3N, because of the instability of some adducts. The reaction tolerates a wide range of α-amido sulfones and different pyrazolones.

Periodic quantum dot solids are new materials in which quantum dots are periodically distributed in space. The properties of these materials are explored to find applications in new photovoltaic devices. In order to shed light on these future applications, investigating carrier transport and light absorption are of paramount importance. The first step to investigate these systems is to compute their electronic structures. In this work we present the electronic structure of one- (1D), two- (2D) and three-dimensional (3D) quantum dot solids made of 12 A radius InAs quantum dots. Two different stoichiometries are studied. In the first case (system A) the quantum dot has an In atom in its center and the interdot contact surfaces along the (111) directions in the arrays are mainly arsenic atoms. In the second case (system B) the atomic positions are inverted, and therefore the contact surfaces between neighbours are mainly indium atoms. The influence of dimensionality and stoichiometry in these quantum dot solids are discussed.

International audience; Aldosterone, the main mineralocorticoid hormone in humans, plays a pivotal role in the control of water and salt reabsorption via activation of the mineralocorticoid receptor (MR). Alterations in MR signaling pathway lead to renal dysfunction, including chronic kidney disease and renal fibrosis, that can be prevented or treated with mineralocorticoid receptor antagonists (MRAs). Here, we used RNA-Sequencing to analyze effects of two MRAs, spironolactone and finerenone, on the aldosterone-induced transcriptome of a human renal cell line stably expressing the MR. Bioinformatics analysis of the data set reveals the identity of hundreds of genes induced or repressed by aldosterone. Their regulation is modulated in a time-dependent manner and, for the induced genes, depends on the aldosterone-driven direct binding of the MR onto its genomic targets that we have previously characterized. Although both MRAs block aldosterone-induced as well as aldosterone-repressed genes qualitatively similarly, finerenone has a quantitatively more efficient antagonism on some aldosterone-induced genes. Our data provide the first complete transcriptome for aldosterone on a human renal cell line and identifies pro-inflammatory markers (IL6, IL11, CCL7, and CXCL8) as aldosterone-repressed genes.

A valuable organocatalytic vinylogous Mannich reaction between alkylidenepyrazolones and isatin-derived ketimines has been successfully established. Squaramide organocatalyst, prepared from quinine, catalyzed the diastereo- and enantioselective vinylogous Mannich addition, affording a range of aminooxindole-pyrazolone adducts (24 examples) with excellent outcomes: up to 98% yield with complete diastereoselectivity and excellent enantioselectivity (up to 99% ee). Additionally, different synthetic transformations were performed with the chiral pyrazolone-oxindole adducts.

Este artículo se encuentra disponible en la siguiente URL: https://www.mdpi.com/1422-0067/22/3/1375 Este artículo pertenece al número especial "The Role of Mesenchymal Stem Cells on Inflammatory and Fibrotic Diseases". Adipose tissue represents an abundant source of mesenchymal stem cells (MSC) for therapeutic purposes. Previous studies have demonstrated the anti-inflammatory potential of adipose tissue-derived MSC (ASC). Extracellular vesicles (EV) present in the conditioned medium (CM) have been shown to mediate the cytoprotective effects of human ASC secretome. Nevertheless, the role of EV in the anti-inflammatory effects of mouse-derived ASC is not known. The current study has investigated the influence of mouse-derived ASC CM and its fractions on the response of mouse-derived peritoneal macrophages against lipopolysaccharide (LPS). CM and its soluble fraction reduced the release of pro-inflammatory cytokines, adenosine triphosphate and nitric oxide in stimulated cells. They also enhanced the migration of neutrophils or monocytes, in the absence or presence of LPS, respectively, which is likely related to the presence of chemokines, and reduced the phagocytic response. The anti-inflammatory effect of CM may be dependent on the regulation of toll-like receptor 4 expression and nuclear factor- B activation. Our results demonstrate the antiinflammatory effects of mouse-derived ASC secretome in mouse-derived peritoneal macrophages stimulated with LPS and show that they are not mediated by EV.

Pyrazolone [2,4-dihydro-3H-pyrazol-4-one] represents one of the most important five-membered nitrogen heterocycles which is present in numerous pharmaceutical drugs and molecules with biological activity. Recently, many catalytic methodologies for the asymmetric synthesis of chiral pyrazolones have been established with great success, specially, for the synthesis of pyrazolones bearing a tetrasubstituted stereocenter at C-4. This review summarizes these excellent research studies since 2018, including representative examples and some mechanistic pathways explaining the observed stereochemistry.1 Introduction2 Catalytic Enantioselective Synthesis of Chiral Pyrazolones with a Full Carbon Tetrasubstituted Stereocenter at C-43 Catalytic Enantioselective Synthesis of Chiral Pyrazolones with a Quaternary Carbon Stereocenter at C-4 bearing a Heteroatom4 Catalytic Enantioselective Synthesis of Chiral Spiropyrazolones5 Conclusion

[EN] Biobased plasticizers, as substitutes for phthalates, have been synthesized from 5-hydroxymethylfurfural (HMF) and carboxylic acids (or esters) through a chemoenzymatic cascade process that involves as its first step the reduction of 5-hydroxymethylfurfural into 2,5-bis(hydroxymethyl)furan (BHMF), followed by the esterification of BHMF with carboxylic acids (or esters) by using a supported lipase (Novozym 435). The reduction of HMF into BHMF is performed by using monodisperse metallic Co nanoparticles with a thin carbon shell (Co@C) with high activity and selectivity. After optimization of reaction conditions (temperature, hydrogen pressure, and solvent), it is possible to achieve 97% conversion of HMF with 99% selectivity to BHMF after 2 h reaction time. The reduction of HMF and esterification of BHMF using carboxylic acids or vinyl esters as acyl donors by lipase are optimized separately in batch and in fixed-bed continuous reactors. The coupling of two flow reactors (for reduction and subsequent esterification) working under optimized reaction conditions affords the diesters of BHMF in roughly 90% yield with no loss of activity during 60 h of operation., The research leading to these results has received funding from the Spanish Ministry of Science, Innovation and Universities through "Severo Ochoa" Excellence Programme (SEV-2016-0683) and the PGC2018-097277-B-100 (MCIU/AEI/FEDER, UE) project. The authors also thank the Microscopy Service of UPV for kind help with measurements. JMC thanks UPV for a predoctoral fellowship.

A bifunctional squaramide catalyzed the enantioselective Michael addition of pyrazol-3- ones to ortho-quinone methides, generated in situ from 2-(1-tosylalkyl)phenols is presented. The corresponding chiral pyrazolones are obtained with good to excellent yields (27-98%) and enantiomeric excess (14-99% ee).

The crude naringinase from Penicillium decumbens and a purified naringinase with high α-L-rhamnosidase activity could be covalently immobilized on two-dimensional zeolite ITQ-2 after surface modification with glutaraldehyde. The influence of pH and temperature on the enzyme activity (in free and immobilized forms) as well as the thermal stability were determined using the specific substrate: p-nitrophenyl-alpha-L-rhamnopyranoside (Rha-pNP). The crude and purified naringinase supported on ITQ-2 were applied in the hydrolysis of naringin, giving the flavonoids naringenin and prunin respectively with a conversion '90 % and excellent selectivity. The supported enzymes showed long term stability, being possible to perform up to 25 consecutive cycles without loss of activity, showing its high potential to produce the valuable citrus flavonoids prunin and naringenin. We have also succeeded in the application of the immobilized crude naringinase on ITQ-2 for debittering grapefruit juices in a continuous process that was maintained operating for 300 h, with excellent results., The authors acknowledge financial support from PGC2018‐097277‐B‐100 (MCIU/AEI/FEDER,UE) project and Program Severo Ochoa (SEV‐2016‐0683). Jilin agreement 111 Project (Grant No. B17020). JMC thanks to Universitat Politècnica de València for predoctoral fellowships.

Valuable chiral alcohols have been obtained from racemic mixtures with an integrated heterogeneous chemoenzymatic catalyst in a two consecutive fixed catalytic bed continuous reactor system. In the first bed the racemic mixture of alcohols is oxidized to the prochiral ketone with a Zr-Beta zeolite and using acetone as the hydrogen acceptor. In the second catalytic bed the prochiral ketone is stereoselectively reduced with an alcohol dehydrogenase (ADH) immobilized on a two dimensional (2D) zeolite. In this process, the alcohol (isopropanol) formed by the reduction of acetone in the first step reduces the cofactor in the second step, and the full reaction cycle is in this way internally closed with 100% atom economy. A conversion of about 95% with ∼100% selectivity to either the (R) or the (S) alcohol has been obtained for a variety of racemic mixtures of alcohols., The research leading to these results has received funding from the Spanish Ministry of Science, Innovation and Universities through “Severo Ochoa” Excellence Programme (SEV-2016-0683) and the PGC2018-097277-B-100(MCIU/AEI/FEDER, UE) project. J. M. C. thanks to Universitat Politécnica de Valencia for a predoctoral fellowship.

In this work we analyzed the photo-production of hydrogen using titania-based systems able to profit from UV and visible light photons. For this purpose, we prepared Niobium-doped titania and a titania reference by a microemulsion method, subjected these oxide precursors to calcination and subsequently introduced Pt as co-catalyst by a chemical reduction method. These materials were characterized in terms of the structural and morphological properties of the oxide and metal phases. Using these materials, we measured the reaction rate and quantum efficiency of the hydrogen photo-production using methanol, ethanol, and 2-propanol as sacrificial agents. Significant activity enhancement was observed in the Niobium-doped material with respect to the titania reference material. The study focuses on interpreting the differences presented (between the two samples) among the three alcohols in the hydrogen yield and provides a physico-chemical study to understand the roots of the activity. Such study was mainly based on the analysis of the reaction mechanism using in-situ infrared spectroscopy together with the analysis of the energetics of the reaction taking into account the fate of the sacrificial alcohol during reaction.

Nb-doped titania nanopowders active under UV and visible light were used as supports of platinum and tested in the photo-production of hydrogen using methanol as sacrificial agent in liquid phase. Samples were characterized using X-ray diffraction and photoelectron spectroscopy, UV–vis and photoluminescence spectroscopies, electron paramagnetic resonance, and transmission electron microscopy. The catalytic performance was evaluated taking into account the measurement of the corresponding reaction rates and the computation of the quantum efficiency values. Optimization of the catalytic output upon UV and visible excitation was carried out as a function of the Nb content of the material and using an experimental design taking as factors the methanol:water ratio, and catalyst concentration at liquid phase. The performance of the materials and the optimum for a catalyst containing a 2.5 mol% of Nb upon UV, visible light and sunlight was examined. The characterization results concerning both the charge carrier species recombination and the fate of such species at the catalytic surface were used to elucidate the physico-chemical roots for maximizing activity.

A relatively low surface area graphitic carbon nitride produced by a standard melamine calcination procedure was subjected to an exfoliation process and/or surface deposition of Mn-containing species. The resulting catalysts were characterized using X-ray diffraction and photoelectron spectroscopies, transmission electron microscopy, UV–vis and infrared spectroscopies, and porosimetry. The photocatalytic properties of the materials were tested in the gas-phase degradation of toluene under UV, visible and Sunlight-type illumination and their performance assessed through the measurement of the materials optical properties and subsequent calculation of the true quantum efficiency. The numerical analysis of the efficiency parameter evolution throughout the above mentioned carbon nitride samples provides quantitative estimation of the catalytic effect resulting from the exfoliation process and/or the surface deposition of Mn-containing species. Such analysis allows thus to compare the activity significance of each one of the carbon nitride modifications explored as well as the synergistic effect originated by the combined action of such modifications.

A series of samples where platinum is deposited onto titania P25 using a chemical deposition method was tested in the photo-production of hydrogen using methanol as a sacrificial agent. The optimization of the platinum titania contact was analyzed as a function of the synthesis conditions. The catalysts’ structural and electronic properties were measured using a combination of porosimetry, X-ray diffraction, X-ray photoelectron, photoluminescence, and UV–visible spectroscopies, together with a microscopy study of the noble metal particle size distribution and an in situ infrared study of the catalysts under reaction conditions. The measurement of the optical properties of the catalyst suspensions and the subsequent calculation of the true quantum efficiency were used to show that a significant enhancement of ca. 250% can be achieved through the series of Pt-containing catalysts. The study provides solid evidence concerning the physical roots of the photoactivity behavior. For catalysts having equal Pt properties in terms of primary particle size and electron handling capability, a synergy between the noble metal and the oxide support at interface sites is shown to promote the conversion of carboxylate-type surface species into carbon dioxide and maximize the hydrogen yield of the reaction.

Despite safety concerns raised by the European Medicines Agency (EMA), evidence supporting QT-lengthening effects of escitalopram is far to be conclusive. We aimed to evaluate the relationship between escitalopram plasma levels (Escit-PL) and corrected QT-interval length (QTc-length) in 91 outpatients recruited from a hospital setting. Fifteen patients had an abnormally prolonged QTc-interval, and 3 had QTc-intervals >= 500 ms. No correlation between Escit-PL and QTc-length was found (r = 0.08; p = 0.45). Linear/logistic regression analyses were also conducted taking into account potential confounders such as age, gender, personal history of heart disease, medication load and concomitant use of antipsychotic/tricyclic antidepressants. Escit-PL did not predict either QTc-length or abnormally prolonged QTc-interval. Only antipsychotics/tricyclics use (adjusted beta = 0.26, SE = 9.1; p = 0.01) was an independent predictor of QTc-length (R (2) = 0.096, F = 4.68, df = 2,88; p = 0.01). Only antipsychotics/tricyclics use (OR 3.56 [95% CI 1.01-12.52]; p < 0.05) and medication load (OR 1.32 [95% CI 1.06-1.64]; p < 0.01) were significantly associated with an increased risk of abnormally prolonged QTc-interval (Omnibus test chi (2) = 9.5, df = 2; p < 0.01). Our study did not find a significant relationship between Escit-PL and QTc-length even when recognized modulating factors of the QT-interval were controlled for. Concomitant use of other potentially arrhythmogenic agents may help to explain the apparent link between escitalopram and QT prolongation previously suggested. The advisability of maintaining the EMA warning is once again called into question.

Biogenic amine contents and microbial contamination (wild yeasts and lactic acid bacteria) were followed during beer fermentation in both industrial and pilot plants. No significant change in the amine contents was observed, except for tryptamine and tyramine. Tyramine formation showed a great variability (from 8 to almost 30 mg/l), while tryptamine formation was always much lower than tyramine (

Screening of cellular activity for inhibitors of histone lysine modifiers is most frequently performed indirectly by analyzing changes in the total levels of histone marks targeted by lysine methylases/demethylases. However, inhibition of histone lysine modifiers often leads to local rather than total changes in histone marks. Also, because histone modifications can be modulated by more than one cellular enzyme, it is not always clear whether changes in histone marks are a direct or indirect consequence of the inhibitor treatment applied. Direct assessment of target occupation can provide a useful tool to quantify the fraction of an epigenetic modifier that is bound to a pharmacological inhibitor (target engagement). Here, we developed and used a novel chemoprobe-based immunoassay to quantify target engagement in cells. Quantification of the fraction of free KDM1A was made possible, in an immune-based assay, by coupling a biotinylated chemoprobe to a warhead capable of selectively and irreversibly binding to the free active form of KDM1A. The results obtained confirmed that this approach is able to determine the degree of target engagement in a dose-dependent manner. Furthermore, the assay can be also used on tissue extracts to analyze the in vivo pharmacokinetics and pharmacodynamics relationship of KDM1A inhibitors, as has been exemplified with ORY-1001 (iadademstat), a potent and irreversible inhibitor of KDM1A. The principle of this assay may be applied to other targets, and the KDM1A probe may be employed in chemoproteomic analyses.

[EN] Production of citrus flavonoids prunin and naringenin was performed selectively through the enzyme hydrolysis of naringin, a flavonoid glycoside abundant in grapefruit wastes. To produce the monoglycoside flavonoid, prunin, crude naringinase from Penicillium decumbens was purified by a single purification step resulting in an enzyme with high -rhamnosidase activity. Both crude and purified enzymes were covalently immobilized on graphene oxide. The activity of the immobilized enzymes at different pH levels and temperatures, and the thermal stability were determined and compared with those exhibited by the free naringinases using specific substrates: p-nitrophenyl--d-glucoside (Glc-pNP) and p-nitrophenyl-alpha-l-rhamnopyranoside (Rha-pNP). The crude and purified naringinase supported on GO were tested in the hydrolysis of naringin, giving naringenin and prunin, respectively, in excellent yields. The supported enzymes can be reused many times without loss of activity. The naringinase stabilized on GO has high potential to produce the valuable citrus flavonoids prunin and naringenin., Authors acknowledge the financial support from MICINN Project CTQ-2015-67592-P and Program Severo Ochoa (SEV-2016-0683). JVC thanks Universitat Politecnica de Valencia for predoctoral fellowships. JY and AC thank the support from the National Natural Science Foundation of China (Grant No. 21320102001) and the 111 Project (Grant No. B17020).

Pyruvate decarboxylase (PDC) is responsible for the decarboxylation of pyruvate, producing acetaldehyde and carbon dioxide and is of high interest for industrial applications. PDC is a very powerful tool in the enzymatic synthesis of chiral amines by combining it with transaminases when alanine is used as amine donor. However, one of the main drawback that hampers its use in biocatalysis is its production and the downstream processing on scale. In this paper, a production process of PDC from Zymobacter palmae has been developed. The enzyme has been cloned and overexpressed in Escherichia coli. It is presented, for the first time, the evaluation of the production of recombinant PDC in a bench‐scale bioreactor, applying a substrate‐limiting fed‐batch strategy which led to a volumetric productivity and a final PDC specific activity of 6942 U L(−1)h(−1) and 3677 U gDCW(−1) (dry cell weight). Finally, PDC was purified in fast protein liquid chromatography equipment by ion exchange chromatography. The developed purification process resulted in 100% purification yield and a purification factor of 3.8.

14 páginas, 6 figuras. Material suplementario en https://doi.org/10.1038/s41419-018-0673-z., Endogenous and synthetic glucocorticoids (GCs) regulate epidermal development and combat skin inflammatory diseases. GC actions can be mediated through the GC receptor (GR) and/or the mineralocorticoid receptor (MR), highly homologous ligand-activated transcription factors. While the role of GR as a potent anti-inflammatory mediator is well known, that of MR is not as clear, nor is whether these receptors cooperate or antagonize each other in the epidermis. To address this, we generated mice with epidermal-specific loss of both receptors (double knockout, DKO), and analyzed the phenotypical and functional consequences relative to single KOs or controls (CO). At birth, DKO epidermis displayed a phenotype of defective differentiation and inflammation, which was more severe than in either single KO, featuring neutrophil-containing infiltrates, and gene dysregulation characteristic of human psoriatic lesions. This phenotype resolved spontaneously. However, in adulthood, single or combined loss of GC receptors increased susceptibility to inflammation and hyperproliferation triggered by phorbol ester which, different to CO, was not effectively counteracted by GC treatment. Also, DKOs were more susceptible to imiquimod-induced psoriasis than CO showing severe defective epidermal differentiation and microabcesses while single KOs showed an intermediate response. Immortalized DKO keratinocytes featured increased proliferation kinetics and reduced cell size, a unique phenotype relative to single KO cells. The lack of GR and MR in keratinocytes, individual or combined, caused constitutive increases in p38 and ERK activities, which were partially reversed upon reinsertion of receptors into DKO cells. DKO keratinocytes also displayed significant increases in AP-1 and NF-κB transcriptional activities, which were partially rescued by ERK and p38 inhibition, respectively. Reinsertion of GR and MR in DKO keratinocytes resulted in physical and cooperative functional interactions that restored the transcriptional response to GCs. In conclusion, our data have revealed that epidermal GR and MR act cooperatively to regulate epidermal development and counteract skin inflammation., This work was supported by grants SAF2014-59474-R and SAF2017-88046-R (MINECO, Spanish Government). J.B. is recipient of FPI fellowship from MINECO (BES2015-072722). We thank COST ADMIRE BM-1301 and NURCAMEIN (SAF2015-71878-REDT and SAF2017-90604-REDT) for support for dissemination.

Previous studies have demonstrated the efficiency of commercial polyaluminum–polyamine coagulants for high silica removal from industrial effluents without pH adjustment. This paper studies the efficiency of newly developed tailor-made hybrid coagulants for silica removal, based on the combination of a commercial polyaluminum nitrate sulfate (PANS) and three polyamines (PAs) of different molecular weights. Four hybrids for each polymer, with different proportions of PANS and polyamine (5, 10, 15, and 20%) were tested at two initial pHs (8.4 and 10.5) and five dosages (in the range 500–2,500 mg/L). Results showed that without pH regulation (pH 8.4), all the hybrids were more efficient than PANS on silica removal, 5% of polyamine being the optimum content (>50 vs. 30% silica removal obtained by PANS). For the same level of efficiency (30% silica removal), the required dosages of hybrids are considerably lower than for PANS: 500 vs. 2,500 mg/L. At initial pH of 10.5, higher silica removal rates are o...

Background aims Excessive or unresolved inflammation leads to tissue lesions. Adipose tissue–derived mesenchymal stromal cells (AMSCs) have shown protective effects that may be dependent on the modulation of inflammation by secreted factors. Methods We used the zymosan-induced mouse air pouch model at two time points (4 h and 18 h) to evaluate the in vivo effects of AMSCs and their conditioned medium (CM) on key steps of the early inflammatory response. We assessed the effects of AMSCs and CM on leukocyte migration and myeloperoxidase activity. The levels of chemokines, cytokines and eicosanoids in exudates were measured by use of enzyme-linked immunoassay or radio-immunoassay. In addition, the expression of cyclooxygenase-2 and microsomal prostaglandin E synthase-1 (mPGES-1) was studied by use of Western blotting and the phosphorylation of p65 nuclear factor-κB (NF-κB) by immunofluorescence. Results All inflammatory parameters were significantly reduced by CM and AMSCs to a similar extent at 4 h after zymosan injection with lower effects at 18 h. The observed inhibition of leukocyte migration was associated with reduced levels of chemokines and leukotriene B 4 . Interleukin-1β, interleukin-6, tumor necrosis factor-α and tumor necrosis factor–stimulated gene 6 levels were significantly decreased. The downregulation of mPGES-1 was associated with inhibition of prostaglandin E 2 production. Our results suggest that these anti-inflammatory effects are related, in part, to the inhibition of NF-κB activation. Conclusions AMSCs dampen the early process of inflammation in the zymosan-induced mouse air pouch model through paracrine mechanisms. These results support the potential utility of these cells as a source of novel treatment approaches for inflammatory pathologies.

Hydrogen sulfide and partially carbon dioxide can be absorbed into alkaline washing liquid with nitrates for upgrading a quality of biogas. Sulfides captured into the washing liquid are consequently biologically oxidized in an anoxic bioreactor by autotrophic denitrifying bacteria. Nitrates in the washing liquid serve as electron acceptors for sulfide bio-oxidation. Washing of hydrogen sulfide from biogas was examined in a lab-scale countercurrent scrubber that was packed with plastic carriers and operated at different biogas and washing liquid flows. The hydrogen sulfide concentration in treated biogas was investigated in the range from 3 to 12.3 g m–3. The influence of the hydrogen sulfide volumetric loading rate on required scrubber wetting Sw was determined. The anoxic bioreactor packed with the same plastic carriers for immobilization of bacteria was operated long term at the sulfide loading rate in the range from 21 g m–3 day–1 during the start-up period to 400 g m–3 day–1 at the end of the operatio...

We have previously shown that the selective sigma-1 receptor (σ1 R) antagonist S1RA (E-52862) inhibits neuropathic pain and activity-induced spinal sensitization in various pre-clinical pain models. In this study we characterized both the behavioral and the spinal neurochemical effects of S1RA in the rat formalin test. Systemic administration of S1RA produced a dose-related attenuation of flinching and lifting/licking behaviors in the formalin test. Neurochemical studies using concentric microdialysis in the ipsilateral dorsal horn of awake, freely moving rats revealed that the systemic S1RA-induced antinociceptive effect occurs concomitantly with an enhancement of noradrenaline levels and an attenuation of formalin-evoked glutamate release in the spinal dorsal horn. Intrathecal pre-treatment with idazoxan prevented the systemic S1RA antinociceptive effect, suggesting that the S1RA antinociception depends on the activation of spinal α2 -adrenoceptors which, in turn, could induce an inhibition of formalin-evoked glutamate release. When administered locally, intrathecal S1RA inhibited only the flinching behavior, whereas intracerebroventricularly or intraplantarly injected also attenuated the lifting/licking behavior. These results suggest that S1RA supraspinally activates the descending noradrenergic pain inhibitory system, which may explain part of its antinociceptive properties in the formalin test; however, effects at other central and peripheral sites also account for the overall effect. Formalin-induced nociceptive effect occurs concomitantly with an enhancement of glutamate (Glu) level in the dorsal horn spinal cord. The selective σ1 receptor antagonist S1RA results in inhibition of formalin-evoked Glu release, no modification of GABA levels, and enhancement of noradrenaline (NA) levels. This increased spinal NA activates spinal α2-adrenoceptors producing the attenuation of the formalin-induced pain behaviour.

Paediatric high grade glioma (pHGG) are defined by recurrent mutations in H3 histones, as well as frequent alterations in the SWI/SNF chromatin remodelling gene ATRX (α-thalassemia mental retardation X-linked), although the precise role of ATRX in tumorigenesis remains unclear. We sought to explore this using genomic analysis of patient samples, CRISPR-Cas9 engineered isogenic ATRX knockout (KO) cell lines and primary-patient-derived cultures. In combined retrospective and prospective cohorts of pHGG samples, we found ATRX mutations in 95/510 (18.6%) cases (27% hemispheric glioblastoma, 13% diffuse midline glioma), with the majority of truncating mutations found in the ADD domain, and missense mutations almost exclusively in the helicase domain. ATRX mutations commonly co-segregate with H3.3G34 and TP53 mutations, and define a subgroup of patients with a longer overall survival, though with a greater number of somatic mutations and copy number alterations than wild-type cases. CRISPR/Cas9-mediated ATRX KO targeting the ADD domain in TP53 mutant paediatric glioblastoma cells lead to loss of imprinting at the H19 locus in concert with upregulation of a pro-invasive transcriptional programme, though a slower rate of orthotopic tumour growth in vivo. ATRX deficient cells showed an abrogated DNA damage response, with prolonged accumulation of gH2AX foci after irradiation, and an increased dependency on PARP1 through persistent parylation and stalled replication forks. Screening ATRX-deficient isogenics and patient-derived cells against a library of >400 chemotherapeutics and small molecules identified a specific dependency for ATRX loss and sensitivity to distinct PARP inhibitor chemotypes, including catalytic inhibitors (olaparib, rucaparib), and PARP trappers (talazoparib). ATRX deficiency further conferred an enhanced radiosensitization of olaparib in vitro and a prolonged survival of mice treated with combined PARP inhibition and radiotherapy in vivo. These data suggest a synthetic lethality for PARP inhibitors in ATRX-deficient pHGG, and may represent a novel therapeutic strategy for these highly aggressive tumours.

The temperature dependent contribution to the R 1 ( 2 E ← 4 A 2 ) linewidth in emerald, Be 3 Al 2 Si 6 O 18 :Cr 3 , has been measured by employing spectral hole-burning, fluorescence line narrowing and conventional luminescence experiments. The contribution varies from 0.6 MHz at 6.5 K to ∼420 GHz at 240 K and the line red-shifts by ∼570 GHz. Above 60 K, the dependence is well described by a non-perturbative formalism for two-phonon Raman scattering. Below this temperature the direct one-phonon process between the levels of the split 2 E excited state dominates. However, it appears that a localized low-energy phonon leads to a deviation from the standard pattern at lowest temperatures.

Background: Primary ciliary dyskinesia (PCD) is a rare disorder characterized by dysfunction of respiratory cilia and impaired mucociliary clearance leading to recurrent airway infection and chronic inflammation appearing in childhood. Rationale and aims: Chronic inflammation has been associated to oxidative stress (OS). Moreover, evidence of increased OS in the airways of stable children with PCD has been shown (Zihlif, N. et al . Pediatr Pulmonol 2006; 41:509-14). We hypothesize that OS would be increased in ciliated nasal epithelial cells (CNEC) from patients with PCD. This study was aimed to assess the OS profile in CNEC isolated from children with PCD. Methods: CNEC were obtained from ten children diagnosed with PCD, ten PCD- like patients and ten control individuals. OS parameters were prospectively measured by flow cytometry. Results: PCD patients showed significantly higher reduced glutathione (GSH) (p=0.01) and total superoxide anion (O 2 - ) (p=0.03) but lower nitric oxide (NO) levels (p=0.05) than the control and PCD- like patients. PCD patients and PCD-like patients show higher oxidized/reduced lipid ratio (p=0.30), carbonylated proteins (CP) (p=0.14) and mitochondrial O 2 - (mO 2 - ) (p=0.16) than the control group although the results did not reach statistical significance. No significant differences were observed in mitochondrial parameters and H 2 O 2 between groups. Conclusions: PCD patients exhibit a pro-oxidant oxidative profile. PCD-like patients show a similar behaviour as PCD patients in levels of mO 2 - , NO, and CP, whereas a comparable behaviour to controls in total O 2 - and GSH levels. Our results suggest an implication of OS in the pathophysiology of PCD.

Introduction: Nasal nitric oxide (nNO) has been proposed as a screening tool for primary ciliary dyskinesia (PCD). However, there are no reference values by age in consensus guidelines. Objectives: 1) To analyze differences in nNO among a group of patients with PCD and healthy controls. 2) To determine the proportion of pediatric PCD patients with nNO values similar to healthy population. Methods: Determination of nNO by electrochemical system (NIOX Vario®) in patients with DCP (diagnosis confirmed by digital high speed videomicroscopy) and healthy controls (without asthma, rhinitis or atopic dermatitis), aged between 7 and 60 years. Results: 32 patients (17 children, 53.1%) and 32 controls (18 children, 56.2%) were included. nNO differences were globally significant in both groups (161.4 ppb in PCD vs 2338.8 ppb in controls, p Conclusions: nNO may be normal in a high percentage of PCD children, so its role as a screening method in this group of age should be considered with caution. Definitive diagnostic tests should be performed in case of high clinical suspicion of the desease.

[EN] Context: The efficacy of the combination chondroitin sulfate-glucosamine (CS-GlcN) in the treatment of knee osteoarthritis (OA) has been suggested in recent clinical studies. In vitro reports have also suggested anti-inflammatory and anti-resorptive effects of this combination. Objective: The aim of this study was to characterize the effects of CS-GlcN on joint degradation in vivo including the assessment of inflammation and bone metabolism in a model of OA. Materials and methods: We have used the OA model induced by anterior cruciate ligament transection (ACLT) in ovariectomised rats. CS-GlcN was administered daily (oral gavage) from week 0 until week 12 after ovariectomy at the dose of 140 (CS) + 175 (GlcN)(HCl) mg/kg. Histochemical analyses were performed, the levels of biomarkers and inflammatory mediators were measured by luminex or ELISA and bone microstructure was determined by mCT. Results: CS-GlcN protected against cartilage degradation and reduced the levels of inflammatory mediators such as interleukin-1b and tumor necrosis factor-a in the affected knee. In addition, serum biomarkers of inflammation and cartilage and bone degradation including matrix metalloproteinase-3, C-telopeptide of type II collagen and the ratio receptor activator of nuclear factor kB ligand/ osteoprotegerin were significantly decreased by CS-GlcN. This treatment also tended to improve some bone microstructural parameters without reaching statistical significance. Discussion and conclusions: These results demonstrate the chondroprotective effects of CS-GlcN in vivo, in the experimental model of ACLT in ovariectomised rats, and suggest that this combination may be useful to control the joint catabolic effects of inflammatory stress. These findings could have clinical relevance related to the prevention of joint degradation by CS-GlcN and support the potential development of OA treatments based on this combination., The authors thank Ms. Anna Blanco for her technical assistance. The present study was supported by grants from Bioiberica S.A. and Spanish Ministerio de Economia y Competitividad, ISCIII, FEDER (RETICEF RD12/0043/0013). The funding sources had no role in the conduct of the study; collection, management, analysis, interpretation of the data; and preparation of the manuscript. A.T., P.D., R.R., E.M. and J.V. are employed by Bioiberica S.A.

The enhancement of active triggered by surface deposition of Cu, Bi, and Ce containing oxidic species onto a high surface area anatase is analyzed through the calculation of the quantum efficiency for toluene photodegradation under UV and Sunlight-type illumination. To this end, series of Cu, Bi, and Ce containing oxides supported on anatase were synthesized having a growing content of the Cu, Bi, and Ce surface species and characterized with X-ray diffraction and photoelectron, UV-visible, and photoluminescence spectroscopies as well as transmission electron microscopy. Utilizing the surface concentration of Cu, Bi, and Ce species as a tool, we analyzed the influence of the system physicochemical properties affecting quantum efficiency in anatase-based materials. First, employing small surface concentrations of the Cu, Bi, and Ce species deposited onto (the unperturbed) anatase, we provided evidence that all steps of the photocatalytic event, including light absorption, charge recombination, as well as surface interaction with the pollutant and chemical output as to activity and selectivity have significance in the quantitative assessment of the enhancement of the efficiency parameter. Second, we analyzed samples rendering maximum quantum efficiency within all these series of materials. The study indicates that maximum enhancement over anatase displays a magnitude strongly dependent on the efficiency level of calculation and would thus require the use of the most accurate one, and that it occurs through a balance between optoelectronic and chemical properties of the composite materials. The (Cu, Bi, Ce) oxide-anatase interface plays a major role modulating the optoelectronic properties of the solids and thus the efficiency observable, Financial support by MINECO (ENE2013-46624-C4-1-R) is gratefully acknowledged

3 páginas, 2 figuras. Contiene material suplemenario, Glucocorticoid (GC) hormones can bind two structurally and functionally related steroid receptors: the GC Receptor (GR or Nr3c1) and the mineralocorticoid receptor (MR or Nr3c2), which recognize the same DNA response elements and act as ligand-dependent transcription factors. While the crucial role of GR for skin homeostasis has been widely characterized, the exact role of MR in this tissue deserves further study. We assessed NR3C2 expression in developing and adult WT mouse skin and found a transient peak at embryonic day (E)16.5, which along with low levels of HSD11B2, the enzyme inactivating GCs, supports a role for GC-MR complexes in epidermal maturation. Consistent with this observation, MR-/- embryonic skin showed alterations in early epidermal differentiation that resolved postnatally. The lack of a more severe skin phenotype of MR-/- mice suggests functional compensation by GR in this tissue in the perinatal period., This work was supported by JSPS KAKENHI grant numbers 25870545 and 15K09772. Spanish Ministerio de Ciencia e Innovación. Grant Numbers: SAF2011-28115, SAF2014-59474-R

Measurement of neurotransmitters in the spinal dorsal horn in conscious animals remains a technical challenge. Here we applied concentric microdialysis to measure formalin-induced glutamate (Glu) release in the ipsilateral dorsal horn in conscious, freely-moving rats. Hind paw formalin injection induced flinching nociceptive behaviors accompanied by increased Glu in the dorsal horn (maximum = 294%). Both flinching and Glu increase were prevented by morphine (3 mg/kg, s.c.). Accordingly, concentric microdialysis is a sensitive technique for studying neurochemical modulation induced by pain and analgesics in the spinal dorsal horn of awake rats. Measurement of Glu provides information on modulation of excitatory signals. Keywords:: concentric microdialysis, glutamate, dorsal horn

Histone Lysine demethylases (KDMs) are emerging clinical targets in cancer. However, a characterization of the mechanism of action of KDMs small molecule inhibitors is limited by the fact that these targets act at multiple levels, having several substrates, different scaffolding roles and regulating gene expression in a cell-specific manner. We developed biotinylated chemoprobes capable of binding to the active site of different KDMs and demonstrated their versatility in target engagement and chemoproteomics analysis. First, we synthetized a biotinylated chemoprobe capable of binding selectively and irreversibly to the active form of KDM1A. By coupling the chemoprobe to an immune-based assay, we can quantify the levels of free KDM1A relative to total levels of KDM1A in a dose-dependent manner in vitro and in vivo. Using this assay, we measured the KDM1A target engagement in models for AML and SCLC. These data were used to perform quantitative pharmacological modeling of SCLC xenograft models treated with ORY-1001 (see Medhi et al, AACR 2018 submitted abstract). The technique can be readily applied to clinical samples and has been used to characterize the pharmacokinetic / pharmacodynamic relationship of KDM1A inhibitors in Phase I trials. In addition, we show that the proteomic profile of the chemoprobe pulldown mirrors the binding partners of inhibited KDM1A. Our proteomic analysis using the KDM1A specific chemoprobe in AML cells identified several ZNF transcription factors but SNAG domain proteins, known to bind to the inhibitor binding site, were not retrieved, providing insight in the interaction changes induced by a KDM1A inhibitor. The strategy was also applied to other targets such as Jumonji C (JmjC) domain-containing proteins like the KDM5 demethylase family, reported to play a role in the emergence of drug tolerance. Overall, this study offers important insights and tools for investigating the role of KDM inhibitors in cancer and their further development into the clinical setting. Citation Format: Serena Lunardi, Filippo Ciceri, Cristina Mascaró Crusat, Raquel Ruiz, Elena Carceller, Alberto Ortega, Natalia Sacilotto, Paola Dessanti, Jordi Salas, Michele Lufino, Tamara Maes. Novel multi-functional chemoprobes for the characterization of the mechanism of action of histone lysine demethylases inhibitors in cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr LB-003.

Metallic silver (ranging from 1 to 10 wt %) was deposited onto a graphite-like carbon nitride photocatalyst through a microemultion method. Surface, morphological, and structural properties of the resulting materials were characterized using BET and porosity measurements, X-ray diffraction, X-ray photoelectron spectroscopy, transmission electron microscopy, and UV-vis and photoluminescence spectroscopy. The activity of the composite samples under sunlight-type and visible illumination was measured for toluene photodegradation and was analyzed by means of the reaction rate and the quantum efficiency parameter. To obtain the latter observable, the lamp emission properties as well as the radiation field interaction with the catalyst inside the reactor were modeled and numerically calculated. The stability of the samples under both illumination conditions was also studied. The results evidence that the composite samples containing 1-10 silver wt % outperform carbon nitride for sunlight-type and visible illumination, but the optimal use of the charge generated after light absorption is obtained for the sample with 1 wt % of silver acording to the quantum efficiency calculation. The study shows that the optimum silver-g-C3N4 contact is able to outperform TiO2 reference systems (nano-TiO2 and P25) under sunlight illumination and points out that this occurs as a direct consequence of the charge handling through the interface between catalyst components. This indicates that composite systems based on g-C3N4 can be competitive in sunlight-triggered photodegradation processes to eliminate tough polluctants such as toluene, rendering active and stable systems.

Ten patients with craniopharyngioma treated for the first time when younger than 18 were included. This study reviews the visual outcomes and provides information on visual field (VF) and optical coherence tomography (OCT) examination of craniopharyngioma. The best kappa concordance coefficients between VF and OCT parameters of atrophy were obtained for the ganglion cell (GC) thickness and the mean retinal nerve fibre layer (RNFL) thickness. The agreement between GC colour maps and VF defects was good. Optic nerve compression may be detected by RNFL measurement and GC analysis, and this may be valuable to predict visual recovery and in uncooperative patients to evaluate visual damage.

An equation that includes the effects of non-parabolicity on the conduction band of a semiconductor is applied to different nanosystems. This allows us to obtain analytical expressions in systems with simple geometries and reveals significant differences in relation to those obtained in parabolic cases. For quantum wells, we propose an empirical energy–wave vector dispersion relationship that can be used in electron transport simulation. In the case of quantum dots, by choosing suitable parameter values, the results obtained using the non-parabolic model are adjusted to those produced by tight binding. The introduction of non-parabolicity corrections is shown to greatly modify the energy spectrum. To illustrate this fact, we use as an example a system useful in a quantum dot laser.

The nuclear transcription factor kappaB (NF-kappaB) is a cytoplasmic dimer that, as the family of mitogen-activated protein kinase (MAPK), can directly regulate the expression of early genes and genes involved in the stress response, following a variety of physiological or pathological stimuli. Both of them stimulate the transcription of many proteins, which are considered important during inflammation. A crucial role has been assigned to these factors in cellular proliferation and in neointimal hyperplasia secondary to the endothelial lesion of arterial vessels. On the other hand, it has been described that neomycin can have an inhibitory function on tumor cell proliferation, through the inhibition of different intracellular pathways of signaling, among them the NF-kappaB and MAPK pathways. Rat common carotid artery was subjected to balloon angioplasty. Neomycin sulfate (18 mg) was applied using pluronic acid gel on the adventitial surface of the injured vessel. MAPK and NF-kappaB activation was quantified after 24 hours with immunohistochemical staining. Neointimal formation was quantified after 14 days with morphometry. Immunohistochemistry results demonstrating MAPK and NF-kappaB activation reveal that both transcription factors are activated in the media of the control vessel wall. In contrast, the immunoreactivity for MAPK and NF-kappaB in the sections obtained from arteries treated with neomycin over 24 hours was insufficient or nonexistent. Treatment with neomycin on adventitia over 14 days in arteries on which angioplasty was performed shows a neointimal index (intimal area/medial area) decrease of 71% in comparison with arteries that were not treated. The adventitial neomycin treatment over 14 days produces a very significant increase (287.5%; p0.0001) in the arterial luminal circumference in comparison with arteries treated with vehicle. These results support the theory that neomycin plays an important role against neointimal hyperplasia through the inhibition of MAPK and NF-kappaB activation.

Electron transport properties in double-gate-silicon-on-insulator (DGSOI) transistors are comprehensively studied. Quantum effects are analyzed by self-consistently solving the 1 D Poisson and Schroedinger equations. Once the electron distribution is known, the Bolztmann transport equation is solved by the Monte Carlo method, and the role of volume inversion is analyzed both at room and at lower temperatures. A comparison between symmetrical-gate and asymmetrical-gate configurations is also provided, showing the superior performance of symmetric devices. Finally, velocity overshoot is also studied. Monte Carlo simulations were performed to clarify the dependence of velocity overshoot effects on the low-field mobility, channel inversion charge and silicon layer thickness. We show that electron mobility is mainly determined by the increase in the phonon scattering rate as the silicon thickness is reduced, i.e., the lower the silicon thickness the lower the electron mobility, while velocity overshoot effects for ultrathin DGSOI inversion layers are dominated by the reduction of the average conduction effective mass, i.e., the lower the silicon thickness the higher the velocity overshoot peak.

We have studied the influence of the image and exchange-correlation effects in double-gate silicon on insulator (DGSOI) devices, in the calculation of both charge distribution and of electron mobility. We find that the image and exchange correlation potentials produce a greater confinement of the carriers and, according to the uncertainty principle, a greater phonon scattering rate, which produces a decrease in electron mobility. We have also observed that the influence of image and exchange-correlation potentials on electron mobility, while almost negligible for bulk silicon inversion layers, becomes increasingly important as the silicon thickness decreases, due to the effect of volume inversion in DGSOI reversion layers. It is thus essential to take these effects into account in order to correctly evaluate the inversion charge distribution and the electron mobility in DGSOI inversion layers.

This study examines the electrical and temperature behavior of two of the levels in Czochralski-grown silicon that are most detected by different authors. A comparison between an analytical expression of the generation recombination noise in p−n junctions with experimental data taken from other authors was used as a tool for determining capture cross sections and densities of oxygen related traps in silicon. The parameters found in the literature for a deep level located at EC−0.43 eV are verified in this work. Parameters for a shallower level, a Coulomb trap with an activation energy of 0.17 eV, are also obtained. To correlate our theoretical results, obtained by noise analysis, with those of other authors, obtained with different techniques, thermally activated and field enhanced transitions between the latter center and the conduction band are considered. A thorough theoretical study of a silicon p−n junction with these levels shows a mutable electrical operation of the shallower center, acting as an e...

We have studied electron mobility behavior in asymmetric double-gate silicon on insulator (DGSOI) inversion layers, and compared it to the mobility in symmetric double-gate silicon on insulator devices, where volume inversion has previously been shown to play a very important role, being responsible for the enhancement of the electron mobility. Poisson’s and Schroedinger’s equations have been self-consistently solved in these structures to study and compare the distribution of the electrons. We show that the lack of symmetry in the asymmetric DGSOI structure produces the loss of the volume inversion effect. In addition, we show that as the silicon thickness is reduced the conduction effective mass of electrons in asymmetric devices is lower than that in the symmetric case, but that the greater confinement of electrons in the former case produces a stronger increase in the phonon scattering rate, and in the surface roughness scattering rate. We have solved the Boltzmann transport equation by the Monte Carl...

Lolium multiflorum (Italian ryegrass), an annual weed invading wheat and barley cropping systems, has evolved resistance to diclofop-methyl (DM) herbicide. Earlier studies on the mode of action of DM in susceptible L. multiflorum and L. rigidum populations have shown that herbicide promotes oxidative stress leading to senescence, a process reversible through the action of auxins. The disruption of cell membrane potential (E m ) appears to be correlated with DM phytotoxicity in susceptible populations, suggesting that the continuous H extrusion from plasmalemma to extracellular space is inhibited. L. multiflorum usually establishes a symbiotic relationship with fungal endophytes of the Neotyphodium genus. This fungus confers to host plants higher survival at sublethal dosages of DM, probably due to the production of auxinic compounds. Our goal was to characterize DM-resistant and DM-susceptible L. multiflorum populations infected (E +) and non-infected (E-) with endophytes, by studying the capacity of H + bumping of plasmalemma of intact roots under DM selection. We correlated the effects of DM on H + disruption with plant survival. DM inhibited acidification markedly more in susceptible than in resistant populations. Continued extrusion of H by DM-resistant cell membranes was positively related to plant survival and growth. There was no detectable difference in the capacity of bumping H + between DM-susceptible E+ and E- seedlings, even though survival was higher in E+ plants. The basis for the differential response in H + extrusion between resistant and susceptible populations of L. multiflorum is discussed.

We studied the effect of the depletion charge in the polysilicon gate on electron mobility in ultrathin oxide MOSFETs. An improved theory for remote-charge-scattering-limited mobility in silicon inversion layers is developed. The model takes into account the effects of image charges, screening, inversion layer quantization, the contribution of different subbands, oxide thickness, the actual distribution of charged centres inside the structure, the actual distribution of carriers in the inversion layer, the correlation of charged centres and the charged centre sign. It is shown that if the oxide is thin enough the remote Coulomb scattering due to the depletion charge in the poly-gate becomes an effective scattering mechanism, whose effect is comparable to those of the main scattering mechanisms that control the movement of the carriers in the MOSFET channel. As a consequence, this scattering mechanism must be taken into account in order to satisfactorily explain the experimental results obtained in ultrathin oxide MOSFETs. The model is implemented in a Monte Carlo simulator, where the effects of the ionized impurity charge in the substrate, the interface trapped charge and the contribution of other scattering mechanisms are taken into account simultaneously. Our results show that RCS cannot be neglected for oxide thicknesses below 2 nm, but that its effects for tox > 5 nm are negligible. Good agreement with experimental results was obtained.