Planar channeling in bent crystals has been observed in LHC with multi-TeV proton beam in 2015. Two crystals, mounted on novel high-accuracy goniometers (one in the horizontal and one in the vertical ...plane), are integrated in the LHC collimation system, for studying the feasibility of the crystal-based collimation scheme. Using this experimental setup, tests with fully-stripped lead ion beams at both 450 Z and 6500 Z GeV were carried during dedicated LHC beam time. Planar channeling was observed for the first time with lead ions at these unprecedented energies surpassing by more than 1 order of magnitude the previous state-of-the-art for lead heavy ions and providing an important experimental basis for future applications of bent crystals in beam manipulations. The set of measurements performed to confirm this observation, as the local loss reduction in presence of channeling and the evidence of a deflected beam downstream of the crystal, are presented.
Among other potential applications, mesoporous titania with high surface area and crystalline framework is attractive in photocatalytic hydrogen production. The mesoporous structure with pore walls ...formed by nanocrystals of anatase would provide a shorter distance of the electron-hole pairs to reach the photocatalyst surface and a higher surface area to deposit modifiers of its photocatalytic activity. In this work, we have successfully applied a hard-templating pathway to obtain ordered mesoporous titania (m-TiO sub(2)) with high surface area and anatase as main crystalline phase. Subsequently, various amounts of metallic Pt have been deposited using different impregnation methods. All reactions performed exhibit, at short times, a rapid increase in the hydrogen production rate until a point in which a nearly constant value is achieved. The material prepared by the "citrate method", based on reduction and encapsulation with sodium citrate of Pt nanoparticles before the photocatalytic reaction, leads to the highest hydrogen production rates with the shortest time to reach the change on the trend of the activity curve. The reason of this result is that citrate method provides very good dispersion and, specially, because the Pt nanoparticles are deposited and reduced preferentially within the pores of m-TiO sub(2), leading to stronger interactions than the other two explored dispersion routes (wetness impregnation and photodeposition). Thus, despite introducing less than half of the theoretical amount of Pt, citrate method produces close to twice the amount of hydrogen obtained by the other dispersion routes. This production capacity is even higher when the amount of Pt loaded is increased, with the optimal concentration being determined as 2% (w/w).
Decomposition of CH
4 (natural gas) is one of the alternatives under study to achieve the sustainable production of hydrogen. No CO
2 or other greenhouse gases emissions are produced in this route ...and carbon is obtained as a solid co-product at the end of the reaction (
CH
4
⇆
C
+
2
H
2
). This process can be thermally or catalytically conducted and recent studies have demonstrated that the carbon obtained in the reaction can also show catalytic activity.
In this work, thermal and autocatalytic decomposition of methane were studied and compared with the steam reforming with and without CO
2 capture and storage from an environmental point of view, using life cycle assessment (LCA) tools. As well, different energetic scenarios were included in the study.
The selected functional unit was 1
Nm
3 of hydrogen and the LCA was focused on material and raw materials acquisition and manufacturing stages. The assessment was carried out with SimaPro 7.1 software by using Eco-indicator 95 method. Results showed that autocatalytic decomposition is the most environmental-friendly process for hydrogen production since presented the lowest total environmental impact and CO
2 emissions. Also, steam reforming with CO
2 capture and storage led to lower CO
2 emissions but higher total environmental impact than conventional steam reforming.
Conquering obesity has become a major socioeconomic challenge. Here, we show that reduced expression of the miR-25-93-106b cluster, or miR-93 alone, increases fat mass and, subsequently, insulin ...resistance. Mechanistically, we discovered an intricate interplay between enhanced adipocyte precursor turnover and increased adipogenesis. First, miR-93 controls Tbx3, thereby limiting self-renewal in early adipocyte precursors. Second, miR-93 inhibits the metabolic target Sirt7, which we identified as a major driver of in vivo adipogenesis via induction of differentiation and maturation of early adipocyte precursors. Using mouse parabiosis, obesity in mir-25-93-106b–/– mice could be rescued by restoring levels of circulating miRNA and subsequent inhibition of Tbx3 and Sirt7. Downregulation of miR-93 also occurred in obese ob/ob mice, and this phenocopy of mir-25-93-106b–/– was partially reversible with injection of miR-93 mimics. Our data establish miR-93 as a negative regulator of adipogenesis and a potential therapeutic option for obesity and the metabolic syndrome.
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•Knockout of the miR-25-93-106b cluster increased fat mass and insulin resistance•MiR-93 controls Tbx3 and thereby limits self-renewal of early adipocyte precursors•MiR-93 further inhibits the metabolic target Sirt7 and thus in vivo adipogenesis•(Circulating) miR-93 reduced obesity in miR-25-93-106b KO and ob/ob mice
Cioffi et al. provide evidence that miRNA-93 suppresses Tbx3 and Sirt7, thereby controlling expansion of adipocyte precursors and inhibiting adipogenesis, respectively.
New processes under development for producing hydrogen have been assessed using a life cycle methodology and compared to conventional ones. The aim of this paper is to determine the main obstacles to ...be beaten or the critical aspects to be addressed to ensure the feasibility of these processes. Water photosplitting, solar two-step thermochemical cycles and automaintained methane decomposition with different lay-outs were studied. They have been compared to methane steam reforming with CCS and electrolysis with different electricity sources.
The results show the good behaviour of the automaintained methane decomposition. This process is one of the best options when the greenhouse effect emissions are evaluated. Nevertheless, the consumption of a great amount of a non-renewable resource, i.e., natural gas, as reagent can be negative. The two-step thermochemical cycles based on NiFe2O4 is also an interesting option, but its behaviour depends largely on the infrastructure materials employed on the installations. The most promising option is photosplitting with CdS as catalysts. This process shows the best performance.
► New hydrogen production processes compared to conventional ones. ► Life cycle assessment, energy and exergy cumulative demands were estimated. ► Photosplitting: environmental high potential, but its efficiency is low. ► Methane decomposition: clean process, but not sustainable due to methane’s fossil origin. ► Thermochemical cycles: good performance to be improved with higher reaction conversion.
Methane decomposition to yield hydrogen and carbon (CH
4
⇆
2H
2
+
C) is one of the cleanest alternatives, free of CO
2 emissions, for producing hydrogen from fossil fuels. This reaction can be ...catalyzed by metals, although they suffer a fast deactivation process, or by carbonaceous materials, which present the advantage of producing the catalyst from the carbon obtained in the reaction. In this work, the environmental performance of methane decomposition catalyzed by carbonaceous catalysts has been evaluated through Life Cycle Assessment tools, comparing it to other decomposition processes and steam methane reforming coupled to carbon capture systems. The results obtained showed that the decomposition using the autogenerated carbonaceous as catalyst is the best option when reaction conversions higher than 65% are attained. These were confirmed by 2015 and 2030 forecastings. Moreover, its environmental performance is highly increased when the produced carbon is used in other commercial applications. Thus, for a methane conversion of 70%, the application of 50% of the produced carbon would lead to a virtually zero-emissions process.
Obesity is a metabolic chronic disease with important associated morbidities and mortality. Bariatric surgery is the most effective treatment for maintaining long-term weight loss in severe obesity ...and, consequently, for decreasing obesity-related complications, including chronic inflammation.
To explore changes in components of the inflammasome machinery after bariatric surgery and their relation with clinical/biochemical parameters at baseline and 6 months after bariatric surgery.
Twenty-two patients with morbid-obesity that underwent bariatric surgery (sleeve gastrectomy and Roux-en-Y gastric bypass) were included. Epidemiological/clinical/anthropometric/biochemical evaluation was performed at baseline and 6 months after bariatric surgery. Inflammasome components and inflammatory-associated factors nucleotide-binding oligomerization domain-like receptors (NLRs), inflammasome activation components, cytokines and inflammation/apoptosis-related components, and cell-cycle and DNA-damage regulators) were evaluated in peripheral blood mononuclear cells (PBMCs) at baseline and 6 months after bariatric surgery. Clinical molecular correlations/associations were analyzed. Functional parameters (lipid accumulation/viability/apoptosis) were analyzed in response to specific inflammasome components silencing in liver HepG2 cells).
A profound dysregulation of inflammasome components after bariatric surgery was found, especially in NLRs and cell-cycle and DNA damage regulators. Several components were associated with baseline metabolic comorbidities including type 2 diabetes (C-C motif chemokine ligand 2/C-X-C motif chemokine receptor 1/sirtuin 1), hypertension (absent in melanoma 2/ASC/purinergic receptor P2X 7), and dyslipidemia C-X-C motif chemokine ligand 3 (CXCL3)/NLR family pyrin domain containing (NLRP) 7) and displayed changes in their molecular profile 6 months after bariatric surgery. The gene expression fingerprint of certain factors NLR family CARD domain containing 4 (NLRC4)/NLRP12/CXCL3)/C-C motif chemokine ligand 8/toll-like receptor 4) accurately differentiated pre- and postoperative PBMCs. Most changes were independent of the performed surgical technique. Silencing of NLRC4/NLRP12 resulted in altered lipid accumulation, apoptosis rate, and cell viability in HepG2 cells.
Bariatric surgery induces a profound alteration in the gene expression pattern of components of the inflammasome machinery in PBMCs. Expression and changes of certain inflammasome components are associated to baseline metabolic comorbidities, including type 2 diabetes, and may be related to the improvement and reversion of some obesity-related comorbidities after bariatric surgery.
Although inhibitors of the renin-angiotensin-aldosterone system can slow the progression of diabetic kidney disease, the residual risk is high. Whether nuclear 1 factor (erythroid-derived 2)-related ...factor 2 activators further reduce this risk is unknown.
We randomly assigned 2185 patients with type 2 diabetes mellitus and stage 4 chronic kidney disease (estimated glomerular filtration rate GFR, 15 to <30 ml per minute per 1.73 m(2) of body-surface area) to bardoxolone methyl, at a daily dose of 20 mg, or placebo. The primary composite outcome was end-stage renal disease (ESRD) or death from cardiovascular causes.
The sponsor and the steering committee terminated the trial on the recommendation of the independent data and safety monitoring committee; the median follow-up was 9 months. A total of 69 of 1088 patients (6%) randomly assigned to bardoxolone methyl and 69 of 1097 (6%) randomly assigned to placebo had a primary composite outcome (hazard ratio in the bardoxolone methyl group vs. the placebo group, 0.98; 95% confidence interval CI, 0.70 to 1.37; P=0.92). In the bardoxolone methyl group, ESRD developed in 43 patients, and 27 patients died from cardiovascular causes; in the placebo group, ESRD developed in 51 patients, and 19 patients died from cardiovascular causes. A total of 96 patients in the bardoxolone methyl group were hospitalized for heart failure or died from heart failure, as compared with 55 in the placebo group (hazard ratio, 1.83; 95% CI, 1.32 to 2.55; P<0.001). Estimated GFR, blood pressure, and the urinary albumin-to-creatinine ratio increased significantly and body weight decreased significantly in the bardoxolone methyl group, as compared with the placebo group.
Among patients with type 2 diabetes mellitus and stage 4 chronic kidney disease, bardoxolone methyl did not reduce the risk of ESRD or death from cardiovascular causes. A higher rate of cardiovascular events with bardoxolone methyl than with placebo prompted termination of the trial. (Funded by Reata Pharmaceuticals; BEACON ClinicalTrials.gov number, NCT01351675.).
Pancreatic neuroendocrine tumors (PanNETs) comprise a heterogeneous group of tumors with growing incidence. Recent molecular analyses provided a precise picture of their genomic and epigenomic ...landscape. Splicing dysregulation is increasingly regarded as a novel cancer hallmark influencing key tumor features. We have previously demonstrated that splicing machinery is markedly dysregulated in PanNETs. Here, we aimed to elucidate the molecular and functional implications of CUGBP ELAV-like family member 4 (CELF4), one of the most altered splicing factors in PanNETs. CELF4 expression was determined in 20 PanNETs, comparing tumor and non-tumoral adjacent tissue. An RNA sequencing (RNA-seq) dataset was analyzed to explore CELF4-linked interrelations among clinical features, gene expression, and splicing events. Two PanNET cell lines were employed to assess CELF4 function in vitro and in vivo. PanNETs display markedly upregulated CELF4 expression, which is closely associated with malignancy features, altered expression of key tumor players, and distinct splicing event profiles. Modulation of CELF4 influenced proliferation in vitro and reduced in vivo xenograft tumor growth. Interestingly, functional assays and RNA-seq analysis revealed that CELF4 silencing altered mTOR signaling pathway, enhancing the effect of everolimus. We demonstrate that CELF4 is dysregulated in PanNETs, where it influences tumor development and aggressiveness, likely by modulating the mTOR pathway, suggesting its potential as therapeutic target.
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Castaño and colleagues show that CELF4, a splicing factor, is significantly upregulated in pancreatic neuroendocrine tumors (PanNETs) and is associated with malignancy. Modulating CELF4 in PanNET models strongly changed transcriptomics and affected proliferation and everolimus response, potentially by influencing the mTOR signaling pathway. These findings suggest CELF4 as a potential therapeutic target.
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