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There is significant environmental concern about chlorinated organic compounds (COCs) in wastewater, surface water, and groundwater due to their low biodegradability and high persistence. In this work, 1,2,4-trichlorobenzene (124-TCB) was selected as a model compound to study its abatement using wet peroxide oxidation at neutral pH with goethite as a heterogeneous catalyst, which was enhanced with visible monochromatic light-emitting diode (LED) light (470 nm). A systematic study of the main operating variables (oxidant and catalyst concentration and irradiance) was accomplished to investigate their influence in the abatement of 124-TCB in water. The reaction was carried out in a well-mixed reactor of glass irradiated by a visible LED light. The hydrogen peroxide concentration was tested from 0 to 18 mM, the goethite concentration within the range 0.1–1.0 g·L−1 and the irradiance from 0.10 to 0.24 W·cm−2 at neutral pH. It was found that this oxidation method is a very efficient technique to abate 124-TCB, reaching a pollutant conversion of 0.9 when using 0.1 g·L−1 of goethite, 18 mM of H2O2, and 0.24 of W·cm−2 . Moreover, the system performance was evaluated using the photonic efficiency (ratio of the moles of 124-TCB abated and the moles of photons arriving at the reactor window). The maximum photonic efficiencies were obtained using the lowest lamp powers and moderate to high catalyst loads. Fil: Lorenzo, David. Universidad Complutense de Madrid; España Fil: Santos, Aurora. Universidad Complutense de Madrid; España Fil: Sánchez-Yepes, Andrés. Universidad Complutense de Madrid; España Fil: Conte, Leandro Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina Fil: Domínguez, Carmen María. Universidad Complutense de Madrid; España

Introduction: Increased oxidative stress is associated with vascular calcification in patients with chronic kidney disease (CKD). We have previously demonstrated that cellular-derived matrix vesicles (MV), but not media-derived MV, are endocytosed in the presence of phosphorus by recipient normal rat vascular smooth muscle cells (VSMC) and induce calcification through ERK1/2 and [Ca2+]i signaling. We hypothesized that these changes were mediated by increased reactive oxygen species (ROS) production. Methods: MV were co-cultured with recipient VSMC in the presence of high phosphorus and ROS production and cell signaling assessed. Results: The results demonstrated MV endocytosis led to increased ROS production in recipient VSMC with no increase in mitochondrial oxygen consumption or oxidative phosphorylation (OXPHOS), indicating the ROS was not from the mitochondria. The use of inhibitors demonstrated that endocytosis of these MV by VSMC led to a signaling cascade in the cytoplasm beginning with ERK1/2 signaling, then increased [Ca2+]i and stimulation of ROS production, mediated by nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX)1/4. Media-derived MV did not induce this cascade, indicating endocytosis itself was not a factor. Furthermore, inhibition of either ERK1/2 activation or [Ca2+]i reduced vascular calcification. Conclusion: We conclude that endocytosis of pro-mineralizing MV can induce a series of signaling events in normal VSMC that culminate in generation of ROS via activation of NOX1/4. Understanding these pathways will allow the development of future targeted therapeutics.

Blood vessel formation generates unique vascular patterns in each individual. The principles governing the apparent stochasticity of this process remain to be elucidated. Using mathematical methods, we find that the transition between two fundamental vascular morphogenetic programs – sprouting angiogenesis and vascular remodeling – is established by a shift on collective front-rear polarity of endothelial cells. We demonstrate that the competition between biochemical (VEGFA) and mechanical (blood flow-induced shear stress) cues controls this collective polarity shift. Shear stress increases tension at focal adhesions overriding VEGFA-driven collective polarization, which relies on tension at adherens junctions. We propose that vascular morphogenetic cues compete to regulate individual cell polarity and migration through tension shifts that translates into tissue-level emergent behaviors, ultimately leading to uniquely organized vascular patterns.

The mitochondrial enzyme dihydroorotate dehydrogenase (DHODH) catalyzes one of the rate-limiting steps in de novo pyrimidine biosynthesis, a pathway that provides essential metabolic precursors for nucleic acids, glycoproteins and phospholipids. DHODH inhibitors (DHODHi) are clinically used for autoimmune diseases and are emerging as a novel class of anti-cancer agents, especially in acute myeloid leukemia (AML) where pyrimidine starvation was recently shown to reverse the characteristic differentiation block in AML cells. Herein we show that DHODH blockade rapidly shuts down protein translation in leukemic stem cells (LSCs) by down-regulation of the multi-functional transcription factor YY1, has potent activity against AML in vivo and is well tolerated with minimal impact on normal blood development. Moreover, we find that ablation of CDK5, a gene that is recurrently deleted in AML and related disorders, increases the sensitivity of AML cells to DHODHi. Our studies provide important molecular insights and identify a potential biomarker for an emerging strategy to target AML.

The use of monoclonal antibodies in cancer therapy is limited by their cross-reactivity to healthy tissue. Tumor targeting has been improved by generating masked antibodies that are selectively activated in the tumor microenvironment, but each such antibody necessitates a custom design. Here, we present a generalizable approach for masking the binding domains of antibodies with a heterodimeric coiled-coil domain that sterically occludes the complementarity-determining regions. On exposure to tumor-associated proteases, such as matrix metalloproteinases 2 and 9, the coiled-coil peptides are cleaved and antigen binding is restored. We test multiple coiled-coil formats and show that the optimized masking domain is broadly applicable to antibodies of interest. Our approach prevents anti-CD3-associated cytokine release in mice and substantially improves circulation half-life by protecting the antibody from an antigen sink. When applied to antibody–drug conjugates, our masked antibodies are preferentially unmasked at the tumor site and have increased anti-tumor efficacy compared with unmasked antibodies in mouse models of cancer. A general approach to mask antibodies using coiled-coil domains improves anti-tumor therapeutic efficacy.

In situ chemical reduction using commercial zero valent iron microparticles (ZVIm) resulted to be an efficient technique for the removal of recalcitrant and toxic chlorinated organic compounds (COCs) dissolved in groundwater. Groundwater was obtained from Bailin’s landfill (Sabinanigo, Spain), where liquid and solid wastes of an old lindane factory were uncontrollably dumped during decades. 28 COCs were identified and quantified by gas chromatographic analysis: five isomers of hexachlorocyclohexane (α, β, e, γ, δ-HCH), benzene, 10 chlorobenzenes and 12 cyclic non-aromatic organochlorine compounds (ΣCOCs = 93 mg L−1). Batch-wise and column experiments were carried out using soil and groundwater from the polluted landfill. It was found that the dechlorination rate increases with the chlorine content of the organic molecule. Non-aromatic COCs with high chlorine content (from 5 to 7 atoms), as well as HCHs, were very rapidly eliminated in the presence of ZVIm via dechloroelimination, while conversions from 60% to 80% were obtained for chlorobenzenes at the end of the treatment, the last ones, dechlorinated via hydrogenolysis. It has been proved that ZVIm appears as an efficient, stable and cost-effective treatment for COCs reduction and the results obtained in the laboratory can be used at full scale. Therefore it was concluded that ZVIm can be used for the on site treatment of the pumped groundwater and also, for the in situ treatment (as permeable reactive barriers (PRBs)) of the groundwater, leading to the complete degradation of the most toxic COCs, those with higher chlorine content, less aromaticity and lower vapor pressure.

Purpose: In this article, we describe a combination chimeric antigen receptor (CAR) T-cell therapy that eradicated the majority of tumors in two immunocompetent murine pancreatic cancer models and a human pancreatic cancer xenograft model. Experimental Design: We used a dual-specific murine CAR T cell that expresses a CAR against the Her2 tumor antigen, and a T-cell receptor (TCR) specific for gp100. As gp100 is also known as pMEL, the dual-specific CAR T cells are thus denoted as CARaMEL cells. A vaccine containing live vaccinia virus coding a gp100 minigene (VV-gp100) was administered to the recipient mice to stimulate CARaMEL cells. The treatment also included the histone deacetylase inhibitor panobinostat (Pano). Results: The combination treatment enabled significant suppression of Her2+ pancreatic cancers leading to the eradication of the majority of the tumors. Besides inducing cancer cell apoptosis, Pano enhanced CAR T-cell gene accessibility and promoted CAR T-cell differentiation into central memory cells. To test the translational potential of this approach, we established a method to transduce human T cells with an anti-Her2 CAR and a gp100-TCR. The exposure of the human T cells to Pano promoted a T-cell central memory phenotype and the combination treatment of human CARaMEL cells and Pano eradicated human pancreatic cancer xenografts in mice. Conclusions: We propose that patients with pancreatic cancer could be treated using a scheme that contains dual-specific CAR T cells, a vaccine that activates the dual-specific CAR T cells through their TCR, and the administration of Pano.

The use of persulfate for the abatement of a wide variety of organic pollutants in soil and groundwater has proved to be an efficient technology in the last 10 years, mainly for in situ application. Persulfate shows higher stability in soil and groundwater than hydrogen peroxide, has moderate cost and benign by-products. Moreover, it can be applied to a wide range of pH and show less affinity for natural organic matter than does the permanganate ion. Persulfate can be activated in different ways to generate free radicals able to react with organic pollutants at higher rates than the persulfate anion. Heat, iron and base are the main activators used, although dual oxidant systems hydrogen peroxide–persulfate has been also investigated. The radical species formed in persulfate activation can be sulfate, hydroxyl or superoxide, depending mainly on pH and the activator used. These radicals can attack the organic matter in an oxidative mechanism, as sulfate and hydroxyl radicals do, or in a reductive pathway, as does the superoxide radical. Therefore, by choosing the proper activator and conditions, activated persulfate system can be used to eliminate a wide range of organic contaminants. Moreover, the stability of the activators in the subsurface is critical to assess the feasibility for an in situ application and must be taken into account to choose the optimal method for each particular case.

Pharmacological inhibition of epigenetic enzymes can have therapeutic benefit, particularly against hematological malignancies. While these agents can affect tumor cell growth and proliferation, recent studies have demonstrated that pharmacological de-regulation of epigenetic modifiers may additionally mediate anti-tumor immune responses. Here we discovered a novel mechanism of immune regulation through the inhibition of histone deacetylases (HDACs). In a genetically engineered model of t(8;21) AML, leukemia cell differentiation and therapeutic benefit mediated by the HDAC inhibitor panobinostat required activation of the type I interferon (IFN) signaling pathway. Plasmacytoid dendritic cells (pDCs) were identified as the cells producing type I IFN in response to panobinostat, through transcriptional activation of IFN genes concomitant with increased H3K27 acetylation at these loci. Depletion of pDCs abrogated panobinostat-mediated activation of type I IFN signaling in leukemia cells and impaired therapeutic efficacy, while combined treatment of panobinostat and recombinant IFNα improved therapeutic outcomes. These discoveries offer a new therapeutic approach for t(8;21) AML and demonstrate that epigenetic rewiring of pDCs enhances anti-tumor immunity, opening the possibility of exploiting this cell type as a new target for immunotherapy.

The intensive use of organochlorine pesticides, such as lindane (γ-HCH), and the inadequate management of their wastes, is a huge environmental problem. The lindane production during the last century has generated huge volumes of solid wastes of other HCH isomers, causing hot points of soil and groundwater contamination. The soil treated in this work was obtained from a landfill located in the nearby of an old lindane factory, containing α-HCH and β-HCH as main contaminants. This study addresses for the first time the application of different chemical oxidation treatments, viz. Fenton process (H2O2 + Fe), persulfate (PS) activated by temperature (20 and 40 °C), by alkali (NaOH) and by the combination of alkali and temperature (NaOH, 40 °C) for the remediation of HCH-polluted soils (CHCHs = 155 mg kg−1). The intrinsic characteristics of the soil (high carbonate content) led to high consumption of H2O2 (XH2O2 ≈ 100% at 24 h) and complete iron precipitation, making unappropriated the application of the Fenton process. The efficiency of thermal PS was limited by the low solubility of HCH isomers in the aqueous phase, the high refractoriness of these compounds towards oxidation, and the presence of the contaminants in the form of particulate matter. After 25 days of treatment, a conversion of chlorinated organic compounds (COCs) of 50% was achieved (VL/Wsoil = 2, CPS = 40 g L−1, 40 °C), whereas the application of PS activated by alkali and temperature (40 °C) led to promising results. At pH above 12, HCHs were dehydrochlorinated to trichlorobenzenes, which were further oxidized by hydroxyl radicals. The hydrolysis rate of β-HCH was the limiting step of the process, and it was favored by increasing the reaction temperature. At 40 °C, a conversion of COCs above 95% was achieved (VL/Wsoil = 2, CPS = 40 g L−1, CNaOH = 13.5 g L−1, 14 days) with low oxidant consumption (XPS = 30%).

Background and importance According to the PARAMOUNT trial, induction chemotherapy with a platin/pemetrexed combination and pemetrexed maintenance therapy reduced the risk of progression free survival (PFS) and overall survival (OS) in patients with non-cell lung cancer (NSCLC). Aim and objectives The aim of the study was to assess the effectiveness and safety of this drug combination in NSCLC and to evaluate the degree of agreement with the PARAMOUNT results. Material and methods A descriptive retrospective study was conducted. All patients that initiated treatment with platin/pemetrexed from January 2018 to September 2019 were included. Clinical data were obtained from digital clinical history and the prescription software Farmis Oncofarm: sex, age, stage, performance status (PS), periodicity of chemotherapy, dose received and number of cycles. PFS and OS were used as efficacy end points, and were obtained by the Kaplan–Meier method (SPSS Statistics programme). In terms of safety, adverse events (AE) of any grade were recorded for assessment of the safety profile. Effectiveness data and safety were compared with the PARAMOUNT results. Results Forty-two patients were enrolled, 36 men and 6 women, with an average age of 67 years (range 42–80). Cancer stage was as follows: stage IV (90%), stage IIB (7%) and stage IIIA (3%). Baseline PS was 0–1 in 60% of cases and in the remainder, 2–3. All patients received as induction therapy on day 1, 21 day cycles of pemetrexed (500 mg/m2) in combination with cisplatin 75 mg/m2 (n=16) or carboplatin AUC=5 (n=26). Pemetrexed maintenance therapy (500 mg/m2) was administrated until progression or death. The median number of cycles was 4 (1–16). Median PFS was 4 months (95% CI 3 to 5) and median OS was 17 months (95% CI 11 to 21). In the PARAMOUNT study, median PFS was 4 months and median OS was 14 months. Sixty per cent of patients (n=25) had AE. The most common AE were mucositis (n=7), asthenia (n=6), diarrhoea (n=3), dermatitis (n=3), vomiting (n=3), anaemia (n=2) and neutropenia (n=2). In the clinical trial, the most common AE of any grade were anaemia, neutropenia, fatigue and nausea. Conclusion and relevance PFS and OS showed a clinical benefit. The safety profile for the use of this combination showed it was tolerated. The effectiveness and AE were similar compared with the published clinical trial. References and/or acknowledgements No conflict of interest.

Background and importance Regorafenib, ramucirumab and cabozantinib are used as secondline therapy in patients with hepatocarcinoma and alfa-fetoprotein value ≥400 ng/mL (HCC-AP ≥400). There are no direct comparisons among them. Aim and objectives To establish whether regorafenib, ramucirumab and cabozantinib are equivalent therapeutic alternatives (ATE) in the secondline treatment of HCC-AP ≥400 through an indirect treatment comparison (ITC) using a common comparator. Material and methods A search was conducted to identify phase III clinical trials with similar populations (secondline treatment of HCC-AP ≥400), duration and endpoints. If more than one study of the same drug was found, the results were combined in a meta-analysis (Joaquim Primo calculator). ITC was made according to Bucher’s method. The variable selected to determine clinical equivalence was overall survival (OS). Delta value (Δ), maximum acceptable difference as a clinical criterion of non-inferiority, was set at 0.750 (and its inverse, 1.33), the value used in trials to calculate sample size. To establish positioning, the criteria of the ATE guide were applied. If 95% CI deviated from the delta margin, this probability was calculated using the Shakespeare method. Results Four clinical trials were found, ramucirumab (n=2), regorafenib (n=1) and cabozantinib (n=1). Limitations found: included population (only patients with alpha-fetoprotein ≥400 ng/mL versus all patients, then subgroup data were used for ITC) and previous therapy as firstline (only sorafenib vs other treatments allowed, in small percentages). Ramucirumab trials were pooled, resulting in HR 0.71 (95% CI 0.58 to 0.86). The results of the ITC are shown in table 1. According to the ATE guide, there was a likely clinical equivalence. The probability that the result exceeded the delta margin above and below was, respectively, 12.45% and 5.76% for cabozantinib–regorafenib, 9.57% and 3.71% for ramucirumab–regorafenib, and 5% and 4.86% for ramucirumab–cabozantinib. Conclusion and relevance The ITC showed no statistically significant differences in OS among the drugs. The 95% CI showed a certain grade of uncertainty, exceeding the equivalence margin. According to the ATE guide, there was clinical equivalence among the drugs due to the small percentage of 95% CI outside the equivalence margin. References and/or acknowledgements No conflict of interest.

In this work, we evaluate the feasibility of carbide-derived carbons (CDCs) as reliable and highly efficient adsorbents for the removal of pharmaceuticals from water. CDCs were produced from titanium carbide at temperatures within the range of 800–1400 °C employing chlorine as extraction agent. The materials were physicochemically characterized and tested in the adsorption of two relevant pharmaceuticals (diclofenac (DCF) and metronidazole (MNZ)) in aqueous solutions. We found that the specific surface area in combination with a low functionalized surface plays a key role on the adsorption capacity of the material while the average pore size determines the kinetics of the process. Notably, the CDCs showed an outstanding adsorptive behaviour compared to different conventional carbon materials under the same operating conditions, which was attributed not only to their high surface areas but mainly to their strong hydrophobic properties. The optimum material (specific surface area of 1676 m2 g−1) showed extremely high adsorption capacity values (551 and 410 mg g−1 for DCF and MNZ, respectively). Remarkably, the process was very fast (10 min of equilibrium time) even using low doses of adsorbent (0.3 mg mL−1). The performance of the optimum CDC was also demonstrated in bi-component systems while its versatility was demonstrated in a real wastewater treatment plant (WWTP) effluent, obtaining a good performance in terms of adsorption capacity (up to ∼400 mgDCF g−1) and kinetics (equilibrium time of 10 min). These results demonstrate the promise of CDCs for reliable, effective and fast flow-through tertiary water treatment.

Summary Vocal fold polyp (VFP) is an exophytic gelatinous lesion with an atrophic epithelium. After behavioral and conservative management, phonomicrosurgery is the treatment of choice for VFPs with excellent outcomes in terms of lesion resolution and postoperative vocal function. Office-based potassium titanyl phosphate (KTP) laser ablation is a new treatment modality for VFPs but its efficacy for professional singers has yet to be validated. Reported is a consecutive series of six professional singers (with seven episodes of VFP) who, based on patient and provider preference, underwent in-office KTP laser ablation of VFP. Two polyps required two ablation procedures; otherwise, a single treatment was successful in resolution of VFP at a mean resolution time of 44 days. Singing voice handicap index 10 improved from a mean of 30.8 (range 4–40) to 6.0 (range 0–22). All patients resumed their professional singing careers without vocal limitations. Posttreatment videos were reviewed by three blinded fellowship trained laryngologists, who were not able to accurately predict the laterality of the polyp (52% correct, p = 0.99).

This study is focused on the effective removal of recalcitrant pollutants hexaclorocyclohexanes (HCHs, isomers α, β, γ, and δ) and chlorobenzenes (CBs) present in a real groundwater coming from a landfill of an old lindane factory. Groundwater is characterized by a total organic carbon (TOC) content of 9 mg L−1, pH0 = 7, conductivity = 3.7 mS cm−1, high salt concentration (SO42−, HCO3−, Cl−), and ferrous iron in solution. The experiments were performed using a BDD anode and a carbon felt (CF) cathode at the natural groundwater pH and without addition of supporting electrolyte. The complete depletion of the four HCH isomers and a mineralization degree of 90% were reached at 4-h electrolysis with a current intensity of 400 mA, the residual TOC (0.8 mg L−1) corresponding mainly to formic acid. A parallel series reaction pathway was proposed: HCHs and CBs are transformed into chlorinated and hydroxylated intermediates that are rapidly oxidized to non-toxic carboxylic acids and/or mineralized, leading to a rapid decrease in solution pH.

In this work, in situ chemical oxidation (ISCO) with alkali activated persulfate has been tested for the elimination of HCH isomers and other chlorinated compounds in groundwater from Sabinanigo (Sardas landfill), which was contaminated by solid and liquid wastes illegally dumped in the area by a company producing lindane. Due to the site lithology and the type of pollutants found in groundwater (HCHs and chlorobenzenes) alkali (NaOH) activated persulfate (PS) was selected as oxidant. The influence of variables such as PS concentration (42–200 mM) and NaOH:PS molar ratio (2:1 to 4:1) on chlorinated compound abatement has been studied and a kinetic model to predict the composition of all chlorinated organic compounds (COCs) in the aqueous phase with time was obtained. It was found that a fast initial hydrodechlorination reaction took place in which HCH isomers reacted to trichlorobenzenes (mainly 1,2,4 TCB) at pH ≥ 12. Mono-, di-, tri and tetrachlorobenzenes remaining were oxidized without producing aromatic intermediates. At the condition tested a first order kinetic model for COCs and PS concentration was obtained. Zero order alkali concentration was obtained while pH was being kept at 12 for the whole reaction time.

Epigenetic heterogeneity is emerging as a feature of tumors. In diffuse large B-cell lymphoma (DLBCL), increased cytosine methylation heterogeneity is associated with poor clinical outcome, yet the underlying mechanisms remain unclear. Activation-induced cytidine deaminase (AICDA), an enzyme that mediates affinity maturation and facilitates DNA demethylation in germinal center (GC) B cells, is required for DLBCL pathogenesis and linked to inferior outcome. Here we show that AICDA overexpression causes more aggressive disease in BCL2-driven murine lymphomas. This phenotype is associated with increased cytosine methylation heterogeneity, but not with increased AICDA-mediated somatic mutation burden. Reciprocally, the cytosine methylation heterogeneity characteristic of normal GC B cells is lost upon AICDA depletion. These observations are relevant to human patients, since DLBCLs with high AICDA expression manifest increased methylation heterogeneity vs. AICDA-low DLBCLs. Our results identify AICDA as a driver of epigenetic heterogeneity in B-cell lymphomas with potential significance for other tumors with aberrant expression of cytidine deaminases., In diffuse large B-cell lymphoma (DLBCL) increased epigenetic heterogeneity in the form of cytosine methylation is known to link to a poor clinical outcome. Here, the authors show that AICDA, an enzyme required for DLBCL pathogenesis, increases cytosine methylation heterogeneity.

Water and soil pollution are among the most critical global problems due to population growth, industrial development, and associated resource consumption [...]

Persistent organic contaminants affecting soil and groundwater pose a significant threat to ecosystems and human health. Fenton oxidation is an efficient treatment for removing these pollutants in the aqueous phase at acidic pH. However, the in-situ application of this technology for soil remediation (where pHs around neutrality are required) presents important limitations, such as catalyst (iron) availability and oxidant (H2O2) stability. The addition of chelating agents (CAs), forming complexes with Fe and enabling Fenton reactions under these conditions, so-called chelate-modified Fenton process (MF), tries to overcome the challenges identified in conventional Fenton. Despite the growing interest in this technology, there is not yet a critical review compiling the information needed for its real application. The advantages and drawbacks of MF must be clarified, and the recent achievements should be shared with the scientific community. This review provides a general overview of the application of CAs to enhance the Fenton process for the remediation of soils polluted with the most common organic contaminants, especially for a deep understanding of the activation mechanisms and influential factors. The existing shortcomings and research needs have been highlighted. Finally, future research perspectives on the use of CAs in MF and recommendations have been provided.

The brain and muscle aryl hydrocarbon receptor nuclear translocator–like protein (BMAL)-1 constitutes a major transcriptional regulator of the circadian clock. Here, we explored the impact of conditional deletion of Bmal1 in endothelium and hematopoietic cells in murine models of microvascular and macrovascular injury. We used two models of Bmal1 fx/fx ; Tek-Cre mice, a retinal ischemia/reperfusion model and a neointimal hyperplasia model of the femoral artery. Eyes were enumerated for acellular capillaries and were stained for oxidative damage markers using nitrotyrosine immunohistochemistry. LSK (lineage-negative, stem cell antigen-1–positive, c- Kit –positive) cells were quantified and proliferation assessed. Hematopoiesis is influenced by innervation to the bone marrow, which we assessed using IHC analysis. The number of acellular capillaries increased threefold, and nitrotyrosine staining increased 1.5-fold, in the retinas of Bmal1 fx/fx ; Tek-Cre mice. The number of LSK cells from the Bmal1 fx/fx ; Tek-Cre mice decreased by 1.5-fold and was accompanied by a profound decrease in proliferative potential. Bmal1 fx/fx ; Tek-Cre mice also exhibited evidence of bone marrow denervation, demonstrating a loss of neurofilament-200 staining. Injured femoral arteries showed a 20% increase in neointimal hyperplasia compared with similarly injured wild-type controls. Our study highlights the importance of the circadian clock in maintaining vascular homeostasis and demonstrates that specific deletion of BMAL1 in endothelial and hematopoietic cells results in phenotypic features similar to those of diabetes.

Purpose We investigated whether subthreshold retinal phototherapy (SRPT) was associated with recruitment of bone marrow (BM)-derived cells to the neurosensory retina (NSR) and RPE layer. Methods GFP chimeric mice and wild-type (WT) mice were subjected to SRPT using a slit-lamp infrared laser. Duty cycles of 5%, 10%, 15%, and 20% (0.1 seconds, 250 mW, spot size 50 μm) with 30 applications were placed 50 to 100 μm from the optic disc. In adoptive transfer studies, GFP+ cells were given intravenously immediately after WT mice received SRPT. Immunohistochemistry was done for ionized calcium-binding adapter molecule-1 (IBA-1+), CD45, Griffonia simplicifolia lectin isolectin B4, GFP or cytokeratin). Expression of Ccl2, Il1b, Il6, Hspa1a, Hsp90aa1, Cryab, Hif1a, Cxcl12, and Cxcr4 mRNA and flow cytometry of the NSR and RPE-choroid were performed. Results Within 12 to 24 hours of SRPT, monocytes were detected in the NSR and RPE-choroid. Detection of reparative progenitors in the RPE occurred at 2 weeks using flow cytometry. Recruitment of GFP+ cells to the RPE layer occurred in a duty cycle-dependent manner in chimeric mice and in mice undergoing adoptive transfer. Hspa1a, Hsp90aa1, and Cryab mRNAs increased in the NSR at 2 hours post laser; Hif1a, Cxcl12, Hspa1a increased at 4 hours in the RPE-choroid; and Ccl2, Il1b, Ifng, and Il6 increased at 12 to 24 hours in the RPE-choroid. Conclusions SRPT induces monocyte recruitment to the RPE followed by hematopoietic progenitor cell homing at 2 weeks. Recruitment occurs in a duty cycle-dependent manner and potentially could contribute to the therapeutic efficacy of SRPT.

This report is focused on the dechlorination of lindane, a recalcitrant and refractory pollutant, by zerovalent iron microparticles (ZVIM) in batch and continuous mode. Experimental variables such as initial lindane concentration, ZVIM dosage, and temperature were studied. Batch experiments indicate that the lindane dechlorination is enhanced with the increase of ZVIM dosage and reaction temperature, and is maintained with increasing initial pollutant concentration. Kinetic analyses elucidated that lindane degradation followed a first order reaction for both pollutant and ZVIM concentration. The kinetic model can also accurately predict the results in continuous mode (more realistic conditions), where the high stability of ZVIM has been thoroughly demonstrated. Further studies indicated that coexistence of common ions can (i) not affect (SO42–, Na+, Ca2+, Mg+) or (ii) promote (HCO3–, Cl–) the lindane dechlorination process. The results implied that the use of ZVIM is a potential approach for in situ remed...

In this work, the abatement of several chlorobenzenes commonly found as pollutants in the aqueous phase has been carried out by catalytic wet peroxide oxidation using goethite as the catalyst and hydroxylamine as the promotor. Spiked water with monochlorobenzene and different positional isomers of dichlorobenzene, trichlorobenzene, and tetrachlorobenzene, at concentrations ranging from 0.4 to 16.9 mg L&minus, 1 was treated. Runs were carried out batch-way, at room conditions, without headspace. The heterogeneous catalyst was commercial goethite, with a specific surface area (SBET) of 10.24 m2 g&minus, 1 and a total iron content of 57.3 wt%. Iron acts as a catalyst of hydrogen peroxide decomposition to hydroxyl radicals. Hydroxylamine (in a range from 0 to 4.9 mM) was added to enhance the iron redox cycle from Fe (III) to Fe (II), remarkably increasing the radical production rate and therefore, the conversion of chlorobenzenes. Iron was stable (not leached to the aqueous phase) even at the lowest pH tested (pH = 1). The effect of pH (from 2 to 7), hydrogen peroxide (from 1 to 10 times the stoichiometric dosage), hydroxylamine, and catalyst concentration (from 0.25 to 1 g/L) was studied. Pollutant removal increased with hydroxylamine and hydrogen peroxide concentration. An operating conditions study demonstrated that the higher the hydroxylamine and hydrogen peroxide concentrations, the higher the removal of pollutants. The optimal pH value and catalyst concentration was 3 and 0.5 g L&minus, 1, respectively. Operating with 2.4 mM of hydroxylamine and 10 times the stoichiometric H2O2 amount, a chlorobenzenes conversion of 90% was achieved in 2.5 h. Additionally, no toxic byproducts were obtained.

Carbon tetrachloride (CT), a chlorinated organic compound widely used in the chemical industry during the 20th century, is nowadays a ubiquitous contaminant in groundwater and in situ technologies for its destruction are required. In this work, the degradation of CT by the alkaline activation of persulfate (PS) has been studied. Among the pool of radical species generated (hydroxyl radicals, sulfate radicals and superoxide radicals), O2∙− resulted to be the only species responsible for CT abatement. It has been found that the presence of other solvents less polar than water (hydrogen peroxide, acetone, propanol and methanol) improves CT degradation. Among them, methanol was selected as the most adequate co-solvent, leading to the complete elimination of CT (100 mg L−1, 24 h) with a moderate unproductive consumption of the oxidant. The degradation of CT increased proportionally with the concentration of this solvent (from 0.1 to 10 g L−1). The ratio NaOH:PS (from 1 to 8) did not affect the degradation of CT when working with a constant concentration of PS and highly alkaline conditions were maintained. The removal rate of CT increased as the concentration of PS increased (from 20 to 60 g L−1), while the conversion of this pollutant did not depend on its initial concentration (from 10 to 100 mg L−1). A kinetic model that considers the concentration of PS, MeOH and CT and can predict the concentration of CT with reaction time at different operating conditions, has been developed from the experimental data.

This study aimed to develop and characterize biodegradable films containing mucilage, chitosan and polyvinyl alcohol (PVA) in different concentrations. The films were prepared by casting on glass plates using glycerol as plasticizer. Mechanical properties, water vapor and oxygen barrier, as well as the interaction with water, were measured. The compatibility of the film-forming components and the uniformity of the films were determined by zeta potential and SEM, respectively. The glycerol and mucilage allowed obtaining more hydrophilic films. The barrier properties of the films made from 100 % chitosan were similar to composed films containing PVA up to 40 %. The results of this study suggest that the interaction between chitosan and mucilage could increase water vapor permeability. The films prepared from either 100 % chitosan or PVA showed a more hydrophobic behavior as compared to the composed films. The films were homogenous since no boundary or separation of components was observed, indicating a good compatibility of the components in the films.

Diffuse large B-cell lymphomas (DLBCLs) are aggressive tumors derived from germinal center (GC) B cells. Despite progress in the treatment of DLBCL, approximately 40% of patients relapse or are refractory to the treatment, which usually leads to fatality. DLBCLs are characterized by aberrant DNA methylation and this feature correlates with poor clinical outcome. We and others have shown that deregulated epigenetic mechanisms contribute to lymphoma formation. Particularly, we have demonstrated that TET2, an enzyme that converts methylcytosine (mC) into hydroxymethylcytosine (hmC) and is mutated in ~10% of DLBCLs, is a B-cell tumor suppressor. GC-specific deletion of TET2 (Cg1Cre/Tet2-/-) resulted in accelerated lymphomagenesis in DLBCL mouse models driven by BCL6 overexpression, with 100% Cg1Cre/Tet2-/-;ImBcl6 mice developing lymphoma at 7 months compared to only 50% in ImBcl6 control mice. In addition, TET2 deletion in hematopoietic stem cells (VavCre/Tet2-/-) induced GC B-cell hyperplasia (B220+GL7+CD95+ cells; 10% VavCre/Tet2-/- vs 5% VavCre/Tet2+/+), promoting malignant transformation. Further analysis of the GC reaction revealed that TET2-deficient GC B cells displayed anomalous patterns of DNA methylation. GC B cells from VavCre/Tet2-/- mice presented 1) focal loss of hmC—using hMeDIPseq—with 25,000 differentially hydroxymethylated regions (DHMR) lost compared to VavCre/Tet2+/+ GC B cells and 2) increased mC—using RRBS—with almost 11,000 differentially methylated cytosines (DMCs), 84% hypermethylated, compared to VavCre/Tet2+/+ GC B cells. TET2-mediated reduction of hmC and hypermethylation affected enhancers and promoters, respectively, of genes mediating GC exit and terminal differentiation of GC B cells, especially those regulated at enhancers by the opposing functions of CREBBP and HDAC3. We are currently investigating the potential cooperative role between TET2-mediated hmC and CREBBP-mediated H3K27Ac, supported by reduced H3K27Ac at enhancers activated by CREBBP in VavCre/Tet2-/- GC B cells and mutual exclusion between TET2-mutant and CREBBP-mutant primary DLBCL. RNA sequencing analysis revealed that the genes epigenetically regulated by TET2 were aberrantly repressed in VavCre/Tet2+/+ GC B cells, explaining the observed GC hyperplasia in TET2-deficient GC B cells since these genes control the differentiation of GC B cells into plasma cells. Importantly, TET2-mutant DLBCL primary samples display a similar repressive transcriptional signature associated with GC B-cell terminal differentiation. Our data show how TET2-induced epigenetic changes contribute to lymphoma development and highlight the multilayered nature of the epigenome, which can be therapeutically exploited. We are evaluating the therapeutic potential in TET2-mutant DLBCL of a combinatorial therapy consisting of DNA methylation inhibitors (DNMTi), to revert hypermethylation at promoters, plus specific HDAC3 inhibitors, to compensate for the loss of hmC at enhancers. Citation Format: Pilar M. Dominguez, Wojciech Rosikiewicz, Xiaowen Chen, Hussein Ghamlouch, Said Aoufouchi, Olivier A. Bernard, Ari M. Melnick, Sheng Li, Ricky W. Johnstone. TET2 deficiency alters the epigenome of germinal center B cells, contributing to lymphoma formation [abstract]. In: Proceedings of the AACR Virtual Meeting: Advances in Malignant Lymphoma; 2020 Aug 17-19. Philadelphia (PA): AACR; Blood Cancer Discov 2020;1(3_Suppl):Abstract nr PO-05.

The alkaline activation of persulfate (PS) has been tested in this study as in situ oxidation technology for the abatement of dichloromethane (DCM), a chlorinated volatile organic pollutant commonly found in groundwater due to its wide use as solvent in the chemical industry during the last decades. The addition of an alkali (NaOH) as persulfate activator generates hydroxyl and superoxide radicals, achieving the total degradation of the pollutant (XDCM = 99%, 96 h, CDCM = 1.2 mmol L−1, CPS = 42 mmol L−1, CNAOH = 169 mmol L−1). From the results obtained in the presence of a hydroxyl radical-scavenger (methanol, CMeOH = 313 mmol L−1), it has been concluded that only hydroxyl radicals are responsible of DCM abatement. Trichloroethylene was identified as intermediate compound and formic acid and chloride as degradation products. The conversion of DCM increased as the initial concentration of the pollutant decreased (from 1.2 mmol L−1 to 0.1 mmol L−1), whereas an increase in the oxidant concentration (from 8 to 168 mmol L−1) led to an increase in the degradation rate of the pollutant. Finally, the molar ratio NaOH:PS (in the range 1–4) did not affect the degradation of the pollutant when a pH high enough (>12) was maintained. A kinetic model, able to predict adequately the experimental DCM concentration profiles as a function of the concentration of DCM, PS and NaOH, has been developed. The kinetic model discriminated was zero order, first order and hyperbolic order for NaOH, PS and DCM concentration, respectively.

Chlorinated pesticides were extensively produced in the XX century, generating high amounts of toxic wastes often dumped in the surroundings of the production sites, resulting in hot points of soil and groundwater pollution worldwide. This is the case of Bailin landfill, located in Sabinanigo (Spain), where groundwater is highly polluted with chlorobenzenes (mono, di, tri and tetra) and hexachlorocyclohexanes. This study addresses the abatement of chlorinated organic compounds (COCs) present in the groundwater coming from the Bailin landfill by thermally activated persulfate, PS (TAP). The influence of temperature (30–50 °C) and oxidant concentration (2–40 g L−1) on the efficiency of COCs (initial concentration of COCs = 57.53 mg L−1, determined by the solubility of the pollutants in water) degradation has been investigated. Raising the reaction temperature and PS concentration the degradation of COCs significantly accelerates, as a result of higher production of sulfate radicals. The thermal activation of PS implies side reactions, involving the unproductive decomposition of this oxidant. The activation energy calculated for this reaction (128.48 kJ mol−1) reveals that is slightly more favored by temperature than the oxidation of COCs by sulfate radicals (102.4–115.72 kJ mol−1). At the selected operating conditions (PS = 10 g L−1, 40 °C), the almost complete conversion of COCs and a dechlorination and mineralization degree above 80% were obtained at 168 h reaction time. A kinetic model, able to adequately predict the experimental concentration of COCs when operating at different temperatures and initial concentration of PS has been proposed.

A combined study for understanding the molecular interactions of asphaltenes with molecular species such as ionic liquids (ILs) comprised experimental measurements and computational numerical simulation calculations, using density-functional theory (DFT) with dispersion corrections, molecular dynamics (MD) calculations, and experimental rheological characterization of the heavy crude oils (HCOs), before and after doping with ILs, respectively. The main results show that ILs influence the asphaltenic dimer association by forming supramolecular complexes that modify the properties of crude oils such as viscosity and interfacial tension. The IL–cation and asphaltene−π ligand molecular interactions seem to dominate the interactions between ionic liquids and asphaltenes, where ILs’ high aromaticity index induces a strong interaction with the aromatic hard core of asphaltenes.

Decomposition of N-tosyl-1,2,3-triazoles with rhodium(II) acetate dimer in the presence of alcohols forms synthetically versatile N-(2-alkoxyvinyl)sulfonamides, which react under a variety of conditions to afford useful N- and O-containing compounds. Acid-catalyzed addition of alcohols or thiols to N-(2-alkoxyvinyl)sulfonamide-containing phthalans provides access to ketals and thioketals, respectively. Selective reduction of the vinyl group in N-(2-alkoxyvinyl)sulfonamide-containing phthalans via hydrogenation yields the corresponding phthalan in good yield, whereas reduction with sodium bis(2-methoxyethoxy)aluminumhydride generates a ring-opened phenethylamine analogue. Because the N-(2-alkoxyvinyl)sulfonamide functional group is synthetically versatile, but often hydrolytically unstable, this protocol emphasizes key techniques in preparing, handling, and reacting these pivotal substrates in several useful transformations.

Decomposition of N-tosyl-1,2,3-triazoles with rhodium(II) acetate dimer in the presence of alcohols forms synthetically versatile N-(2-alkoxyvinyl)sulfonamides, which react under a variety of conditions to afford useful N- and O-containing compounds. Acid-catalyzed addition of alcohols or thiols to N-(2-alkoxyvinyl)sulfonamide-containing phthalans provides access to ketals and thioketals, respectively. Selective reduction of the vinyl group in N-(2-alkoxyvinyl)sulfonamide-containing phthalans via hydrogenation yields the corresponding phthalan in good yield, whereas reduction with sodium bis(2-methoxyethoxy)aluminumhydride generates a ring-opened phenethylamine analogue. Because the N-(2-alkoxyvinyl)sulfonamide functional group is synthetically versatile, but often hydrolytically unstable, this protocol emphasizes key techniques in preparing, handling, and reacting these pivotal substrates in several useful transformations.

International audience; Lindane is an organochlorine pesticide broadly used in the last decades. It is persistent and recalcitrant in aquatic environments and difficult to biodegrade. This study is focused on the complete degradation of lindane by an electrochemical advanced oxidation process, the electro-Fenton (EF) process, using a BDD anode and carbon felt (CF) cathode. The influence of the main operating parameters, i.e., applied current intensity (50–1000 mA), catalyst concentration (0.0–0.5 mM) and initial pollutant concentration (5.0–10.0 mg L−1) has been investigated and optimized. The applied current plays a determinant role both in oxidation of lindane and mineralization of its aqueous solution. Taking into account the mineralization current efficiency (MCE) and the specific energy consumption (EC), the applied current of 400 mA was found to be the most convenient value. Catalyst (Fe2+) concentration as low as 0.05 mM, promotes efficiently H2O2 decomposition into hydroxyl radicals improving the efficiency of the process and minimizing the involvement of parasitic reactions. The initial pollutant concentration does not affect the performance of the process. At the optimum operating conditions, the complete degradation of 10 mg L−1 lindane solution and 80% of TOC removal were achieved at 15 min and 4 h, respectively.

The effective removal of recalcitrant organochlorine pesticides including hexachlorocyclohexane (HCH) present in a real groundwater coming from a landfill of an old lindane (γ-HCH) factory was performed by electrochemical oxidation using a BDD anode and a carbon felt cathode. Groundwater (ΣHCHs = 0.42 mg L−1, TOC0 = 9 mg L−1, pH0 = 7, conductivity = 3.7 mS cm−1) was treated as received, achieving the complete depletion of the HCH isomers and a mineralization degree of 90% at 4 h electrolysis at constant current of 400 mA. Initial groundwater contains high chloride concentration (Cl0− = 630 mg L−1) that is progressively decreased due to its oxidation to different oxychlorine species: Cl2, HClO, ClO−, ClO2− ClO3− and ClO4− some of them (Cl2, HClO, ClO−) playing an important role in the oxidation of organic pollutants. The oxidation rate of chloride (and its oxidized intermediates) depends on the applied current value. Although some of the species generated from them are active oxidants, the presence of inorganic salts is detrimental to the efficiency of the electrochemical process when working at current densities above 100 mA due to the high consumption of hydroxyl radicals in wasting reactions. The initial organic carbon content is not crucial for the extension of the process but high organic loads are more profitable for cost effectiveness. The addition of a supporting electrolyte to the solution could be interesting since it increases the conductivity, reducing the cell potential and therefore, decreasing the energy consumption.

This study focuses on the effect of electrode materials on abatement of lindane (an organochlorine pesticide) by electrooxidation process. Comparative performances of different anodic (platinum (Pt), dimensionally stable anode (DSA) and boron-doped diamond (BDD)) and cathodic (carbon sponge (CS), carbon felt (CF) and stainless steel (SS)) materials on lindane electrooxidation and mineralization were investigated. Special attention was paid to determine the role of chlorine active species during the electrooxidation process. The results showed that better performances were obtained when using a BDD anode and CF cathode cell. The influence of the current density was assessed to optimize the oxidation of lindane and the mineralization of its aqueous solution. A quick (10 min) and complete oxidation of 10 mg L−1 lindane solution and relatively high mineralization degree (80% TOC removal) at 4 h electrolysis were achieved at 8.33 mA cm−2 current density. Lindane was quickly oxidized by in-situ generated hydroxyl radicals, (M(•OH)), formed from oxidation of water on the anode (M) surface following pseudo first-order reaction kinetics. Formation of chlorinated and hydroxylated intermediates and carboxylic acids during the treatment were identified and a plausible mineralization pathway of lindane by hydroxyl radicals was proposed.

In the last few years, several works dealing with Fenton oxidation of ionic liquids (ILs) have proved the capability of this technology for their degradation, achieving complete ILs removal and non-toxic effluents. Nevertheless, very little is known about the kinetics of this process, crucial for its potential application. In this work, the effect of several operating conditions, including reaction temperature (50–90 °C), catalyst load (10–50 mg L−1 Fe3+), initial IL concentration (100–2000 mg L−1), and hydrogen peroxide dose (10–200% of the stoichiometric amount for the complete IL mineralization) on 1-butyl-3-methylimidazolium chloride ([C4mim]Cl) oxidation has been investigated. Under the optimum operating conditions (T = 90 °C; [Fe3+]0 = 50 mg L−1; [H2O2]0 = 100% of the stoichiometric amount), the complete removal of [C4mim]Cl (1000 mg L−1) was achieved at 1.5-min reaction time. From the experimental results, a potential kinetic model capable to describe the removal of imidazolium-based ILs by Fenton oxidation has been developed. By fitting the proposed model to the experimental data, the orders of the reaction with respect to IL initial concentration, Fe3+ amount and H2O2 dose were found to be close to 1, with an apparent activation energy of 43.3 kJ mol−1. The model resulted in a reasonable fit within the wide range of operating conditions tested in this work.

Contrary to the common notion that tumor necrotic regions are non-enhancing after contrast administration, recent evidence has shown that necrotic regions exhibit delayed and slow uptake of gadolinium tracer on dynamic contrast-enhanced MRI (DCE MRI). The purpose of this study is to explore whether the mapping of tumor voxels with delayed and slow enhancement on DCE MRI can be used to derive estimates of tumor necrotic fraction. Patient-derived tumor xenograft lines of seven human cancers were implanted in 26 mice which were subjected to DCE MRI performed using a spoiled gradient recalled sequence. Gadolinium tracer concentration was estimated using the variable flip angle technique. To identify tumor voxels exhibiting delayed and slow uptake of contrast medium, clustering analysis was performed using a k-means clustering algorithm that classified tumor voxels according to their contrast enhancement patterns. Comparison of the percentage of tumor voxels exhibiting delayed and slow enhancement with the tumor necrotic fraction estimated on histology showed a strong correlation (r = 0.962, p

Pathophysiological responses to peripheral nerve injury include alterations in the activity, intrinsic membrane properties and excitability of spinal neurons. The intrinsic excitability of α-motoneurons is controlled in part by the expression, regulation, and distribution of membrane-bound ion channels. Ion channels, such as Kv2.1 and SK, which underlie delayed rectifier potassium currents and afterhyperpolarization respectively, are localized in high-density clusters at specific postsynaptic sites ( Deardorff et al., 2013 , Muennich and Fyffe, 2004 ). Previous work has indicated that Kv2.1 channel clustering and kinetics are regulated by a variety of stimuli including ischemia, hypoxia, neuromodulator action and increased activity. Regulation occurs via channel dephosphorylation leading to both declustering and alterations in channel kinetics, thus normalizing activity ( Misonou et al., 2004 , Misonou et al., 2005 , Misonou et al., 2008 , Mohapatra et al., 2009 , Park et al., 2006 ). Here we demonstrate using immunohistochemistry that peripheral nerve injury is also sufficient to alter the surface distribution of Kv2.1 channels on motoneurons. The dynamic changes in channel localization include a rapid progressive decline in cluster size, beginning immediately after axotomy, and reaching maximum within one week. With reinnervation, the organization and size of Kv2.1 clusters do not fully recover. However, in the absence of reinnervation Kv2.1 cluster sizes fully recover. Moreover, unilateral peripheral nerve injury evokes parallel, but smaller effects bilaterally. These results suggest that homeostatic regulation of motoneuron Kv2.1 membrane distribution after axon injury is largely independent of axon reinnervation.

The extensive use of the organochlorine pesticide lindane in the second half of the 20th century generated large volumes of wastes over the world. Among these wastes, a dense non-aqueous phase liquid (DNAPL), mainly composed of chlorobenzenes, hexachlorocyclohexanes and heptachlorocyclohexanes, was dumped in insecure landfills remaining in the subsurface and contaminating the groundwater. A coupled process, combining soil flushing (with a nonionic surfactant) and Fenton oxidation, was proposed to deal with this problem. A commercial surfactant (E-Mulse 3 ®) was used to extract most of the residual DNAPL in soil at column conditions. The resulting surfactant flushing solution (SFS) presented high concentration of chlorinated organic compounds (COCs = 3693 mg L−1). In order to recover the surfactant and abate the COCs, the SFS was treated by Fenton process using three doses of hydrogen peroxide (200%, 100% and 50% of the theoretical stoichiometric amount for the complete mineralization of COCs; maintaining a molar ratio of H2O2:Fe = 32). Conversions of COCs above 80% were obtained when H2O2 doses of 100% and 200% of the stoichiometric amount were used at 144 h and 48 h, respectively. Non-aromatic compounds resulted to be less prone to oxidation by hydroxyl radicals than chlorobenzenes. The oxidation of the surfactant was significantly lower than that of the pollutants; therefore the surfactant capacity was maintained after the oxidation treatment and it could be reused in further flushing steps, improving the economy of the process.

Sites contaminated by Dense Non-Aqueous Liquid Phases (DNAPLs) containing chlorinated compounds are a ubiquitous problem caused by spills or the dumping of wastes with no concern for the environment. Their migration by gravity through the subsurface and their accumulation far below ground level make in-situ treatments the most appropriate remediation technologies. In this work, an aqueous solution containing a non-ionic and biodegradable surfactant was injected in the Sardas alluvial layer contaminated at some points with DNAPL (formed by a mixture of more than 28 chlorinated compounds) from lindane production. A volume of 5.28 m3 of an aqueous surfactant emulsion (13 g L−1) was injected at 14.5 m b g.l in the permeable layer (gravel-sand), at a flow rate of 0.6 m3 h−1 and the groundwater was monitored within a test cell (3.5 m radius) built ad hoc. The flow of the injected fluids in the subsurface was also evaluated using a conservative tracer, bromide (130 mg L−1), added to the surfactant solution. Concentration of contaminants, chloride, bromide and surfactant, surface tension and conductivity were measured at the injection point and at three monitoring points over time. High radial dispersion was noticed resulting in high dilution of the injected fluids. The surfactant was not adsorbed in the soil during the injection time, the adsorption of the surfactant took place in the meantime (15 h) between its injection and the groundwater (GW) extraction. The concentration of chlorinated compounds dissolved from the soil in the surfactant aqueous phase when equilibrium was reached (about 850 mg L−1) is related to the moderate average contamination of the soil in the test cell (about 1230 mg kg−1). In contrast, the extraction of the free DNAPL in the altered marls layer was highly enhanced due to the addition of the surfactant. Finally, it was found that the surfactant and the contamination did not migrate from the capture zone., Chemical engineering; Environmental chemical engineering; Soil pollution; Environmental pollution; Contaminant transport; Lindane wastes; DNAPL; Surfactant; Alluvium; Tracer; Landfill

The etherification of glycerol with tert-butyl alcohol in the presence of acid catalysts gives rise to the production of ethers (monoethers, diethers and triethers) of high added-value, which can be used as oxygenated additives in fuels. This reaction is limited by the thermodynamic equilibrium, which can be modified by the addition of solvents that selectively solubilize the products of interest along with tert-butyl alcohol, leading to the progress of the reaction. In this work, it has been demonstrated that the addition of dibutyl ether allows shifting the reaction equilibrium, increasing the production of diethers. From the study of the main operating conditions, it was determined that an increase in the concentration of the solvent has a positive effect on the selectivity towards the production of diethers, the concentration of the catalyst (a commercial ion exchange resin, Amberlyst 15, named A-15) and the reaction temperature were also determining variables. Working with concentrations of tert-butyl alcohol above the stoichiometric one did not report great advantages. The optimal operating conditions to maximize the conversion of glycerol and the selectivity towards diethers were: 70 &deg, C, 20% catalyst (referred to the total starting mass of the system), the stoichiometric ratio of glycerol:tert-butyl alcohol (G:TB = 1:3) and 1:2 molar ratio of dibutyl ether:tert-butyl alcohol. A study of three consecutive reaction cycles showed the high stability of the catalyst, obtaining identical results.

Silage corn is a fodder with high starch content, organic matter and digestible fibre, and low nitrogen. From an environmental perspective, its use helps to reduce the volume of manure and N (Salcedo, 2011), emissions of NH3 (Merino et al., 2008), N2O (Arriaga et al., 2010), enteric CH4 (Vellinga and Hovingy, 2010), carbon footprint (Nguyen et al., 2013) and increases nitrogen recovered in milk with respect to intake (Arriaga et al., 2009; Dewhurst, 2013). The aim of this study was to estimate whether the partial substitution of pasture (surface) and grass (feed) by forages with known production and nutritive potential (maize or maize and Lolium multiflorum) and higher input needs (seeds, fertilizers, etc.) can contribute to reducing emissions of CO2-eq/kg of milk, using the simulation model DairyCant 1.0 (Salcedo and Perez, 2014).

During the production of lindane (γ-HCH) large volumes of wastes containing α-, β-, and δ-HCH isomers were generated. Hexachlorocyclohexanes (HCHs) are carcinogens and teratogen compounds. Although their production and use are currently banned in most countries, many landfills and sites remain polluted by these compounds. This paper studies a promising and novel alternative for the HCH abatement: dechlorination by zero valent iron microparticles. Synthetic wastewater (0.5 mg/L of α-, β-, γ-, and δ-HCH or 6 mg/L of γ-HCH) and five types of commercial iron microparticles (here named mFe-1, mFe-2, mFe-3, mFe-4, and mFe-5) were used in batch (5 g/L) and continuous (W mFe/Q L = 167 g · h/L) operation mode at room temperature. Iron microparticles were characterized (before and after reaction) by N2 adsorption/desorption isotherms and X-ray diffraction. HCH isomers showed different behavior vs. dechlorination (γ > α > δ > β) according to the axial/equatorial position of the chlorines. The most active iron source among those tested was mFe-1, presenting small particle diameter (70 μm), moderate BET area (35 m2/kg), low oxygen content, and traces of manganese. mFe-1 exhibited high activity and stability both in continuous (X γ-HCH = 70%, W mFe/Q L = 167 g · h/L) and discontinuous (X γ-HCH = 100%, 48 h) operation. Contribution of HCH adsorption over iron microparticles was found negligible being benzene and Cl− the final dechlorination products.

Polymer tantalum capacitor technology was developed in response to demands from the market to lower the ESR of tantalum capacitors while preserving their small case size and high reliability. The technology is promising in several aspects. The higher quality interface between the dielectric and the polymer cathode increases the breakdown voltage of the device, as well as reducing its DC leakage current, even at extreme radiation exposure conditions.

Cellular polymers films have a too soft mechanical characteristic, like elastic compliance due of the internal porosity structure and their high electric insulation that gives the ability of hosting internal electrical dipoles. If a corona discharge is applied to the surface, the high electrical field induces internal discharges which leave a permanent static charge in the polymer cells. A macro dipole of cell dimension is generated producing a quasi-piezoelectric response. The d 33 piezoelectric constant can reach values of about many hundreds of pC/N. Thermally stimulated discharge currents (TSDC) are widely used to characterize charge density and stability of dielectric materials. In our work the relationship between TSDC and d 33 piezoelectric constant of two cellular polymers based on polyethylene and polypropylene films is investigated. Samples were thermally stretched, charged by corona discharge and metallized on both sides. The d 33 piezoelectric constant by quasi-static method was measured and then TSDC were registered. A strong relation between d 33 constants and TSDC curves on both cellular polymers was obtained.

cAMP generated in response to β-adrenoceptor stimulation modulates excitation-contraction coupling via activation of PKA. It is now widely accepted that cAMP signalling is compartmentalised in the heart and that PDEs, the only cAMP degrading enzyme, play a central role in spatial control of signal propagation. We have previously demonstrated that PKA-I and PKA-II isoforms are selectively activated by spatially confined pools of cAMP leading to phosphorylation of specific downstream targets. It has been suggested that selective deregulation of cAMP/PKA signals in specific subcellular compartment may lead to cardiac pathology. Here we investigate cAMP signalling in an in vitro model of cardiomyocyte hypertrophy and explore the role of different PDE families in the control of the local cAMP response to β-adrenoceptor stimulation. We used a real-time FRET-based imaging approach to monitor cAMP dynamics in adult myocytes. Adenoviral vectors carrying RI or RII Epac were generated by fusing the N-terminus of the cAMP FRET reporter Epac-1 and the dimerisation-docking (DD) domain of the regulatory subunit of PKA-I or PKA-II. Adult rat cardiac myocytes expressing the cAMP reporters were treated overnight with 1μM norepinephrine (NE) as a model of in vitro cardiomyocyte hypertrophy. In control cells, upon stimulation with 100nM isoproterenol, we detected a significantly higher cAMP response in the PKA-II compartment compared to the PKA-I compartment. In NE-treated myocytes, the differences between these compartments were abolished. To investigate which PDE family may be responsible for these changes in cAMP compartmentalisation, experiments were performed in the presence of selective PDEs inhibitors. We found that when PDE2 was inhibited with BAY60-7550 in control cells the resulting increase in cAMP was significantly greater in the PKA-I than in the PKA-II compartment. In hypertrophic myocytes, PDE2 inhibition resulted in a much greater increase in cAMP in the PKA-II compartment compared to control cells. Similar results were found with selective PDE4 inhibition with rolipram. Selective inhibition of PDE3 with cilostamide showed a small but significant rise in cAMP response in the PKA-I compartment in control cells. This was not replicated in hypertrophic myocytes. Our findings indicate that spatial control of cAMP/PKA signalling is altered in this in vitro model of hypertrophy, suggesting that in hypertrophic myocytes mechanisms may be activated resulting in altered localisation and/or activity of PDEs. Further studies will be necessary to fully determine the mechanism responsible for the observed changes.

The gas-phase thermal elimination of 2,2-diethoxypropane was found to give ethanol, acetone, and ethylene, while 1,1-diethoxycyclohexane yielded 1-ethoxycyclohexene and ethanol. The kinetics determinations were carried out, with the reaction vessels deactivated with allyl bromide, and the presence of the free radical suppressor cyclohexene and toluene. Temperature and pressure ranges were 240.1-358.3 °C and 38-102 Torr. The elimination reactions are homogeneous, unimolecular, and follow a first-order rate law. The rate coefficients are given by the following Arrhenius equations: for 2,2-diethoxypropane, log k(1) (s(-1)) = (13.04 ± 0.07) - (186.6 ± 0.8) kJ mol(-1) (2.303RT)(-1); for the intermediate 2-ethoxypropene, log k(1) (s(-1)) = (13.36 ± 0.33) - (188.8 ± 3.4) kJ mol(-1) (2.303RT)(-1); and for 1,1-diethoxycyclohexane, log k = (14.02 ± 0.11) - (176.6 ± 1.1) kJ mol(-1) (2.303RT)(-1). Theoretical calculations of these reactions using DFT methods B3LYP, MPW1PW91, and PBEPBE, with 6-31G(d,p) and 6-31++G(d,p) basis set, demonstrated that the elimination of 2,2-diethoxypropane and 1,1-diethoxycyclohexane proceeds through a concerted nonsynchronous four-membered cyclic transition state type of mechanism. The rate-determining factor in these reactions is the elongation of the C-O bond. The intermediate product of 2,2-diethoxypropane elimination, that is, 2-ethoxypropene, further decomposes through a concerted cyclic six-membered cyclic transition state mechanism.

We present the design, fabrication, and characterization of a resonant magnetic field sensor based on Microelectromechanical systems (MEMS). This sensor exploits the Lorentz force principle and uses a Wheatstone bridge of p-type piezoresistors. Its resonant structure is integrated with silicon beams (15 μm wide and 5 μm thick) and an aluminum loop (9 μm wide and 1 μm thick). The sensor operates in its first flexural resonant frequency (22.99 kHz) and has a linear response, a high resolution (43 nT), a sensitivity of 1.94 V·T−1, a quality factor of 96.6 at atmospheric pressure, and power consumption close to 16 mW.

The products formed in 2-methoxytetrahydropyran elimination reaction in the gas phase are 3, 4-dihydro-2H-pyran and methanol. The kinetic study was carried out in a static system, with the vessels deactivated with allyl bromide, and the presence of the free radical suppressor toluene. Temperature and pressure ranges were 400–450 °C and 25–83 Torr, respectively. The process is homogeneous, unimolecular, and follows a first-order rate law. The observed rate coefficient is represented by the following equation: log k (s−1) = (13.95 ± 0.15) − (223.1 ± 2.1) (kJ mol−1) (2.303RT)−1. The reactant exists mainly in two low energy chair-like conformations, with the 2-methoxy group in axial or equatorial position. However, the transition state (TS) for the elimination of the two conformers is the same. Theoretical calculations of this reaction were carried for two possible mechanisms from these conformations by using DFT functionals B3LYP, MPW1PW91, and PBE with the basis set 6-31G(d,p) and 6-31G++(d,p). The calculation results demonstrate that 2-methoxytetrahydropyran exists mainly in two conformations, with the 2-methoy group in axial or equatorial position, that are thermal in equilibrium. The average thermodynamic and kinetic parameters, taking into account the populations of the conformers in the equilibrium, are in good agreement with experimental values at B3LYP/6-31++(d,p) level of theory. Copyright © 2010 John Wiley & Sons, Ltd.