Search

Single and multilayer films of La0.67Sr0.33MnO3 and CoFe2O4 were deposited by spin-coating. The all-alkoxide precursors allowed inorganic gel films of extreme homogeneity to be formed and converted to phase pure complex oxides at low temperatures. La0.67Sr0.33MnO3 films were made with La- and Ca-methoxy-ethoxides and Mn19O12(moe)14(moeH)10 as precursors at 800 °C. The CoFe2O4 films were obtained at extremely low 275 °C, using a new CoFe2-methoxyethoxide precursor. The decomposition and microstructural development on heating was described by TG, TEM, XRD and IR spectroscopy. XRD showed no spurious phases and the unit-cell dimensions coincided quite well with literature values of the targeted phases. The structural, magnetic and electronic properties of these films established their phase purity and high quality with physical properties comparable to films deposited by physical deposition methods. The magnetic and magneto transport results are presented for single, bi- and tri- layer structures. The magnetically soft La0.67Sr0.33MnO3 layer was exchange coupled to the magnetically hard CoFe2O4 layer, giving rise to interesting switching behaviour in magnetism and magneto-transport properties. © 2021 The Authors. European Journal of Inorganic Chemistry published by Wiley-VCH GmbH

A carbothermal nitridation route to nanophase ZrN1-xCx powder using nitrogen gas and a highly homogeneous solution derived carbon-ZrO2 nanocomposite is described. Composites with 2-4 nm sized ZrO2 ...

Carbothermal reduction of Zr-sucrose gels powders into nano-phase ZrC, or ZrC-Zr(C,O) core-shell powders, via a composite of 2–4 nm sized ZrO2 and amorphous carbon, is described. Samples with 1.7–20 sucrose-carbon:Zr ratio gels heated to 1495 °C at 10 °Cmin−1, with 3 and 30 min hold time were studied in detail using; TG, XRD, SEM, TEM, STEM-EDX, and XPS with Ar+-ion etching. After 1495 °C, 3 min, the samples with 12-20C:Zr ratios yielded weakly agglomerated 30 to 40 nm sized ZrC particles, surrounded by a dense 5 nm thick shell of Zr(C,O). With 5C:Zr significant amounts of ZrO2 was present after heating at 1495 °C for 3 min, while after 30 min annealing, ZrC particles without residual amorphous carbon was obtained. Minor amounts of zirconia was found in most samples, which in similarity with the 5 nm Zr(C,O) shell, is believed to stem from post synthesis oxidation.

A low-cost template-free solution chemical route to highly porous nanocrystalline sponges of ZnO-EuO1.5 with 0-5 mol % Eu is presented. The process uses Zn- and Eu-acetate-nitrate and triethanolamine as precursors in methanol. After evaporation of the solvent and heating at 200 °C for 3 min, crystalline ZnO:Eu sponges with minor amounts of organic residues were obtained. Heating to 400 °C replaced the organics with carbonate, which in its turn was decomposed at temperatures below 600 °C, forming ZnO:Eu sponges. Samples heated to 200-1000 °C for 3 min were studied with XRD, SEM, TEM, TG, XPS, and IR spectroscopy. The ZnO:Eu crystallite sizes could be tuned from below 10 nm for sponges prepared at 200-500 °C, to over 100 nm range at 900 °C, without sintering of the overall microstructure. XRD showed the presence of hexagonal ZnO:Eu (or at 700-1000 °C, ZnO:Eu and cubic Eu2O3) as the only phases present. The ZnO:Eu had slightly larger unit cell dimensions than the literature value of ZnO for samples obtained at 200-600 °C, while the unit cells of samples obtained at higher temperatures were quite close to the value of undoped ZnO. XPS showed that Eu was mainly in its 3+ state and well-distributed within the sponges but segregated at the ZnO sponge surface upon heating at 700-1000 °C, in accordance with XRD studies showing Eu2O3 formation.

The detailed structure of ZnO doped with 5 at.% (metal) of the large aliovalent Eu3+-ions was investigated using EXAFS to describe the local Eu and Zn coordination. The microstructure, crystalline phases, contents and ZnO unit-cell parameters for the ZnO:5%Eu sponges synthesised at 200 to 900 oC were obtained by XRD, SEM, and TEM analysis. XRD showed peaks solely of h-ZnO for the 600 oC sample, while heating at 700 oC and higher caused phase separation into h-ZnO:Eu and c-Eu2O3. XRD showed a close to zero increase in ZnO unit cell-volume of ca. 0.4 vol%, compared to un-doped ZnO for the non-phase separated, clean oxide made at 600 oC. The Zn EXAFS data showed an almost intact local ZnO structure. The Eu EXAFS showed an unusually low coordination number (CN) of ca. 5 for the 200-600 oC samples, while the CN increased for higher temperatures, in concert with the formation of c-Eu2O3. 23 DFT-generated theoretical ZnO structures containing Eu-clusters built from 1 to 4 Eu3+-Zn2+-vacancy- Eu3+ pairs were compared with the experimental data. The lowest formation energies and ZnO unit-cell volume increase versus un-doped ZnO (0.6-0.7 vol%), were obtained when combining two or four Eu3+-Zn2+-vacancy- Eu3+ pairs into Eu4 and Eu8 clusters showing an average Eu CN of ca. 5. These theoretically determined lowest energy structures were all in good agreement with the experimental results obtained by EXAFS and XRD. Photoluminescence excitation and emission spectra performed on the ZnO:5at%Eu sponges obtained at various temperatures, showed strong quenching of the characteristic Eu3+ transitions for samples obtained at 600 and 800 °C, most likely due to changes in the ZnO defect states, which are crucial for Eu3+ excitation, and due to self-quenching upon Eu clustering and c- Eu2O3 phase separation. Thus, the optical data further supported Eu clustering found by EXAFS, DFT and XRD techniques, corroborating structure-property relationships in these materials. Overall, as far as we can find, the findings reported herein point to a doping structure very different from those previously proposed in the literature. It demonstrates that the semiconductor ZnO can host molecular-sized clusters of metal-oxides, very dissimilar to ZnO.

Nanocrystalline ZnO sponges doped with 5 mol% EuO1.5 are obtained by heating metal–salt complex based precursor pastes at 200–900 °C for 3 min. X-ray diffraction, transmission electron microscopy, and extended X-ray absorption fine structure (EXAFS) show that phase separation into ZnO:Eu and c-Eu2O3 takes place upon heating at 700 °C or higher. The unit cell of the clean oxide made at 600 °C shows only ≈0.4% volume increase versus undoped ZnO, and EXAFS shows a ZnO local structure that is little affected by the Eu-doping and an average Eu3+ ion coordination number of ≈5.2. Comparisons of 23 density functional theory-generated structures having differently sized Eu-oxide clusters embedded in ZnO identify three structures with four or eight Eu atoms as the most energetically favorable. These clusters exhibit the smallest volume increase compared to undoped ZnO and Eu coordination numbers of 5.2–5.5, all in excellent agreement with experimental data. ZnO defect states are crucial for efficient Eu3+ excitation, while c-Eu2O3 phase separation results in loss of the characteristic Eu3+ photoluminescence. The formation of molecule-like Eu-oxide clusters, entrapped in ZnO, proposed here, may help in understanding the nature of the unexpected high doping levels of lanthanide ions in ZnO that occur virtually without significant change in ZnO unit cell dimensions.

Small intestinal neuroendocrine tumors (SI-NETs) are small, slow growing neoplasms with loss of one copy of chromosome 18 as a common event. Frequently mutated genes on chromosome 18 or elsewhere have not been found so far. The aim of this study was to investigate a possible tumor suppressor role of the transmembrane receptor type tyrosine phosphatase PTPµ (PTPRM at 18p11) in SI-NETs. Immunohistochemistry, quantitative RT-PCR, colony formation assay and quantitative CpG methylation analysis by pyrosequencing were performed. Undetectable/very low levels of PTPRM or aberrant pattern of immunostaining, with both negative and positive areas, were detected in the majority of tumors (33/40), and a significantly reduced mRNA expression in metastases compared to primary tumors was observed. Both the DNA methylation inhibitor 5-aza-2′-deoxycytidine and the S-adenosylhomocysteine hydrolase inhibitor 3-deazaneplanocin A (DZNep) induced PTPRM expression in CNDT2.5 and KRJ-I SI-NET cells. CpG methylation of upstream regulatory regions, the promoter region and the exon 1/intron 1 boundary was detected by pyrosequencing analysis of the two cell lines and not in the analyzed SI-NETs. Overexpression of PTPRM in the SI-NET cell lines reduced cell growth and cell proliferation and induced apoptosis. The tyrosine phosphatase activity of PTPRM was not involved in cell growth inhibition. The results support a role for PTPRM as a dysregulated candidate tumor suppressor gene in SI-NETs and further analyses of the involved mechanisms are warranted.

The optical features and photocatalytic activity of porous undoped and Eu3+-doped zinc oxide (ZnO) sponge-like structures, annealed at various temperatures, were assessed to establish the relations ...

Small intestinal neuroendocrine tumors (SI-NETs) are slow-growing tumors that seem genetically quite stable without highly recurrent mutations, but are epigenetically dysregulated. In contrast to the undetectable expression of the enhancer of zeste homolog 2 (EZH2) histone methyltransferase in the enterochromaffin cells of the small intestine, we found high and differential expression of EZH2 in primary SI-NETs and corresponding metastases. Silencing EZH2 in the SI-NET cell line CNDT2.5 reduced cell proliferation and induced apoptosis. Furthermore, EZH2 knockout inhibited tumor progression in a CNDT2.5 SI-NET xenograft mouse model, and treatment of SI-NET cell lines CNDT2.5 and GOT1 with the EZH2-specific inhibitor CPI-1205 decreased cell viability and promoted apoptosis. Moreover, CPI-1205 treatment reduced migration capacity of CNDT2.5 cells. The EZH2 inhibitor GSK126 also repressed proliferation of CNDT2.5 cells. Recently, metformin has received wide attention as a therapeutic option in diverse cancers. In CNDT2.5 and GOT1 cells, metformin suppressed EZH2 expression, and inhibited cell proliferation. Exposure of GOT1 three-dimensional cell spheroids to CPI-1205 or metformin arrested cell proliferation and decreased spheroid size. These novel findings support a possible role of EZH2 as a candidate oncogene in SI-NETs, and suggest that CPI-1205 and metformin should be further evaluated as therapeutic options for patients with SI-NETs.

Herein, a catalytic reductive fractionation of lignocellulose is presented using a heterogeneous cobalt catalyst and formic acid or formate as a hydrogen donor. The catalytic reductive fractionation of untreated birch wood yields monophenolic compounds in up to 34 wt % yield of total lignin, which corresponds to 76 % of the theoretical maximum yield. Model compound studies revealed that the main role of the cobalt catalyst is to stabilize the reactive intermediates formed during the organosolv pulping by transfer hydrogenation and hydrogenolysis reactions. Additionally, the cobalt catalyst is responsible for depolymerization reactions of lignin fragments through transfer hydrogenolysis reactions, which target the β-O-4' bond. The catalyst could be recycled three times with only negligible decrease in efficiency, showing the robustness of the system.

According to recent literature in the field of sustainability, the circular economy (CE) appears to be a thriving opportunity for creating new businesses, although less attention has been paid to the form in which its principles fit into a comprehensive framework that enables companies to design it in a practical way. This paper presents the methodology that has been adopted to pave the way to a coherent reference framework for circular business model innovation and its outstanding design and implementation, taking into consideration the entire value and supply chain. A unique analysis of recent innovations in circular economy models is provided herein, together with an exhaustive analysis of those elements that enable or hinder their implementation. The main interactions among all those critical elements influencing how organisations innovate and operate cooperatively within a CE ecosystem are also evaluated. In addition, a study of five industrial cases in the pulp and paper industry allowed searching for industrial insights and empirical evidence of the relevance of those elements, including observation, document analysis, and interviews. Lastly, the main outcomes of this research are illustrated using the CE reference framework designed when applied to the aforementioned industrial cases, and relevant insights into future improvements are also provided. This research was funded by European Union, grant number 730305, a collaborative research project entitled “New market niches for the pulp and paper industry waste based on circular economy approaches (paperChain)” from the European Union’s Horizon 2020 research and innovation programme.

An efficient, template-free solution-chemical route to nanostructured ZnO sponges is presented: A mixture of Zn(NO3)2·6H2O, Zn(OAc)2·2H2O, and triethanolamine in methanol was evaporated to a highly viscous liquid and rapidly heated to >200 °C for 1–3 min to achieve highly porous, nanocrystalline sponges of ZnO. The viscous precursor concentrate obtained on evaporation in air was characterized by TG, DSC, and IR spectroscopy, and the product ZnO sponges by XRD, SEM, TEM, and IR spectroscopy. The fast reaction forming ZnO started at 140 °C and finished within a few seconds. Scherrer analysis of the XRD peak broadening showed average crystallite sizes of 8 to 11 nm for ZnO prepared by annealing at 200–450 °C (3 min), while grain growth to 134 nm was observed from 500 to 900 °C (3 min). The ZnO powders obtained at 200–900 °C had cell dimensions of a = 3.25 A and b = 5.21 A, matching the ZnO literature data well. SEM and TEM analyses showed highly porous, bread-like 3D nanostructures built by ca. 30–70 nm thic...

Primary hyperparathyroidism (pHPT) is rarely caused by parathyroid carcinoma (PC, TET1andTET2play important roles in various cancers. Recently, we found that 5hmC was severely reduced in all of the analyzed PCs and with deranged expression of TET1 for the majority of PCs. Here, we have examined the expression of the TET2 protein in 15 5hmC-negative PCs from patients who had local invasion or metastases. Cell growth and cell migratory roles for TET2 as well as epigenetic deregulated expression were addressed. Immunohistochemistry revealed very low/undetectable expression of TET2 in all PCs and verified for two PCs that were available for western blotting analysis. Knockdown of TET2 in the parathyroid cell line sHPT-1 resulted in increased cell growth and increased cell migration. DNA sequencing ofTET2in PCs revealed two common variants and no obvious inactivating mutations. Quantitative bisulfite pyrosequencing analysis of theTET2promoter CpG island revealed higher CpG methylation level in the PCs compared to that in normal tissues and treatment of a PC primary cell culture with the DNA methylation inhibitor 5-aza-2′-deoxycytidine caused increased expression of the methylatedTET2gene. Hence, the data suggest that deregulated expression ofTET2by DNA hypermethylation may contribute to the aberrantly low level of 5hmC in PCs and further that TET2 plays a cell growth and cell migratory regulatory role and may constitute a parathyroid tumor suppressor gene.

For an integrated steel plant, the blast furnace (BF) is the most energy intensive process unit in which coke and pulverized coal (PC) are used as reducing agents and energy carriers, leading to hu ...

The sintering of a 14 ​wt% nickel nano-dot coated NbC powder was investigated using dilatometry in combination with XRD, ToF-ERDA, PIXE, SEM-EDS/EBSD/TKD, and TEM-HAADF/EDS/EELS for analysis of samples heated to 1375, 1405 and 1500 ​°C, with a 30 ​min annealing. The main sintering step at 1110–1375 ​°C, was succeeded by a slower step, centred at 1405 ​°C, before the final smaller densification step to 1500 ​°C. NbC grain-growth took place on heating at 1500 ​°C for 30 ​min; from ca. 0.5–5 ​μm (average 1 ​μm) at 1375 and 1405 ​°C to ca. 5–30 ​μm (average 10 ​μm) 1500 ​°C for 30 ​min. The NbC0.91-0.94 phase showed a micro-hardness of 1700–2300 HV0.05. The binder phase consisted of the unprecedented textured c-Nb0.15Ni0.85 and h-Nb0.2Ni0.8 phases. The Nb–Ni binder phase yielded micro-hardness values of 1150–1250 (1375–1405 ​°C) to 810 HV0.05 (1500 ​°C, 30 ​min), which greatly exceeds nickel and is higher than Fe3Al.

Small intestinal neuroendocrine tumors (SI-NETs) are amine- and peptide-producing neoplasms. Most patients display metastases at the time of diagnosis; they have an unpredictable individual disease course and the tumors are often therapy resistant. Chromogranin A and 5-hydroxyindoleacetic acid are the biomarkers clinically used most often today, but there is a great need for novel diagnostic and prognostic biomarkers and new therapeutic targets. Sixty-nine biomarkers were screened in serum from 23 SI-NET patients and 23 healthy controls using the multiplex proximity ligation assay (PLA). A refined method, the proximity extension assay (PEA), was used to analyze 76 additional biomarkers. Statistical testing and multivariate classification were performed. Immunohistochemistry and ELISA were performed in an extended cohort. Using PLA, 19 biomarkers showed a significant difference in serum concentrations between patients and controls, and PEA revealed a difference in the concentrations of 17 proteins. Multivariate classification analysis revealed decoy receptor 3 (DcR3), trefoil factor 3 (TFF3), and midkine to be good biomarkers for the disease, which was confirmed by ELISA analysis. All 3 biomarkers were expressed in tumor tissue. DcR3 concentrations were elevated in patients with stage IV disease. High concentrations of DcR3 and TFF3 were correlated to poor survival. DcR3, TFF3, and midkine exhibited elevated serum concentrations in SI-NET patients compared to healthy controls, and DcR3 and TFF3 were associated with poor survival. DcR3 seems to be a marker for liver metastases, while TFF3 and midkine may be new diagnostic biomarkers for SI-NETs.

Neuroendocrine tumour of the small intestine (SI-NET), formerly known as midgut carcinoid tumour, is the most common small intestinal malignancy. The incidence is rising, with recent reports of 0.67 per 100 000 in the USA and 1.12 per 100 000 in Sweden. SI-NETs often present a challenge in terms of diagnosis and treatment, as patients often have widespread disease and are beyond cure by surgery. Somatostatin analogues provide the mainstay of medical treatment to control hormonal excess and increase the time to progression. Despite overall favourable prognosis (5-year overall survival of 65%), there is a need to find markers to identify both patients with worse outcome and new targets for therapy. Loss on chromosome 18 has been reported in 60-90% of SI-NETs, but mutated genes on this chromosome have failed detection. Recently, a putative tumour suppressor role has been suggested for TCEB3C occurring at 18q21 (encoding elongin A3), which may undergo epigenetic repression. CDKN1B has recently been revealed as the only recurrently mutated gene in SI-NETs but, with a frequency as low as 8%, its role as a driver in SI-NET development may be questioned. Integrated genomewide analysis including exome and whole-genome sequencing, gene expression, DNA methylation and copy number analysis has identified three novel molecular subtypes of SI-NET with differing clinical outcome. DNA methylation analysis has demonstrated that SI-NETs have significant epigenetic dysregulation in 70-80% of tumours. In this review, we focus on understanding of the genetic, epigenetic and molecular events that lead to development and progression of SI-NETs.

Primary hyperparathyroidism (pHPT) is a common endocrine disease characterized by excessive secretion of parathyroid hormone and an increased level of serum calcium. Overall, 80–85% of pHPT cases are due to a benign, single parathyroid adenoma (PA), and 15% to multiglandular disease (multiple adenomas/hyperplasia). Parathyroid carcinoma (PC) is rare, accounting for

A fast, low cost solution route to nickel dot coated NbC powder using Ni(NO3)26H2O, Ni(OAc)24H2O and triethanolamine (TEA) as precursors in methanol solvent was developed. After mixing the precursor solution with 50–300 ​nm sized NbC powder and evaporation of the solvent, heating to 150 ​°C, or higher, yielded NbC powder evenly covered with well-dispersed nickel metal dots, 6–25 ​nm in size, depending on the nickel loading and temperature. Coatings yielding 4 to 14 ​wt% nickel loading were studied at temperatures from 200 to 700 ​°C, using TG-DTA, XRD, SEM, XPS with Ar+-ion etching, TEM/DF, and STEM/HAADF/EDS.

European Neuroendocrine Tumor Society staging, together with the Ki67 grading system, has appeared as superior for classification of neuroendocrine tumors (NET). The management of small intestinal NET (SI-NET) has been overall controversial. Mesenteric metastases occur also with the smallest SI-NET, and the majority of patients risk to ultimately progress with liver metastases. 68Gallium (somatostatin receptor)/PET/CT has appeared as most sensitive for imaging, and fluorodeoxyglucose-PET is recommended to identify lesions with high proliferation. Our treatment policy for SI-NET is to initiate somatostatin analog treatment, and in order to prevent abdominal complications we recommend early intestinal resection for removal of primary tumors and clearance of lymph node metastases. Liver metastases are liberally treated by resection (or ablation), as this can efficiently palliate carcinoid syndrome-associated symptoms.

Until recently, the genetic landscape of small intestinal neuroendocrine tumors (SI-NETs) was limited to recurrent copy number alterations, most commonly a loss on chromosome 18. Intertumor heterogeneity with nonconcordant genotype in paired primary and metastatic lesions also is described, further contributing to the difficulty of unraveling the genetic enigma of SI-NETs. A recent study analyzing 55 SI-NET exomes nominated CDKN1B (p27) as a haploinsufficient tumor suppressor gene.This study aimed to determine the frequency of CDKN1B inactivation and to investigate genotype-phenotype correlations. It investigated 362 tumors from 200 patients. All samples were resequenced for mutations in CDKN1B using automated Sanger sequencing. The expression of p27 was investigated in 12 CDKN1B mutant and nine wild type tumors.Some 8.5 % (17/200) of patients had tumors with pathogenic mutations in CDKN1B including 13 insertion deletions, four nonsense variants, and one stop-loss variant. All variants with available nontumoral DNA were classified as somatic. Inter- and intratumor heterogeneity at the CDKN1B locus was detected respectively in six of ten and two of ten patients. Patients with CDKN1B mutated tumors had both heterogeneous disease presentation and diverse prognosis. Expression of the p27 protein did not correlate with CDKN1B mutation status, and no differences in the clinical characteristics between CDKN1B mutated and CDKN1B wild type tumor carriers were found.This study corroborates the finding of CDKN1B as a potential haplo-insufficient tumor suppressor gene characterized by inter- and intratumor heterogeneity in SI-NETs.

Primary hyperparathyroidism (pHPT) is rarely caused by parathyroid carcinoma (PC,1-5% of pHPT cases). The TET proteins oxidize the epigenetic mark 5-methylcytosine to 5-hydroxymethylcytosine (5hmC) and inactivation by mutation or epigenetic deregulation of

Background One-fifth of all patients with small-intestinal neuroendocrine tumors (SI-NETs) present with or develop peritoneal carcinomatosis (PC). Our aim was to determine the prognosis and genetic profiles of tumors in patients with PC compared with tumors in patients without PC. Methods We included SI-NET patients (cases with PC, n = 73, and controls without PC, n = 468) who underwent operation between 1985 and 2012. The Lyon prognostic index was used to correlate the amount of PC to survival. DNA samples from patients with ( n = 8) and without ( n = 7) PC were analyzed with a single-nucleotide polymorphism array (HumanOmni2.5 BeadChip, Illumina) to investigate genetic disparities between groups. Results Patients with PC had poorer survival (median 5.1 years) than controls (11.1 years). An advanced postoperative Lyon prognostic index was a negative prognostic marker for survival by multivariable analysis ( P = .042). Patients with and without PC clustered differently based on loss of heterozygosity and copy number variation data from single-nucleotide polymorphism array of the primary tumors ( P = .042). Conclusion SI-NET patients with PC have poor survival, which diminishes with increasing PC load after surgery. Clustering based on copy number variation and loss of heterozygosity data suggests different genotypes in primary tumors comparing patients with and without PC.

The genetic background in small intestinal neuroendocrine tumors is poorly understood, but several studies have revealed numerical imbalances. Loss of one copy of chromosome 18 is the most frequent genetic aberration in this tumor type, which indirectly suggests that a driver mutation may be present in the remaining allele. The aim of this study was to evaluate the mutation status on chromosome 18 in small intestinal neuroendocrine tumors. DNAs from 7 small intestinal neuroendocrine tumors were subjected to whole exome capture, followed by next generation sequencing and high resolution SNP array followed by copy number variation analysis. Exome capture sequencing generated an average coverage of 50.6-138.2. Only 19 genes were covered less than 8X. No tumor-specific somatic mutation was identified. Genomic profiling revealed loss of chromosome 18 in 5 out of 7 small intestinal neuroendocrine tumors and a number of other aberrancies. Loss of chromosome 18 is the most frequent genetic aberration in small intestinal neuroendocrine tumors, but no evidence for eventual mutations in the remaining allele. This suggests involvement of other mechanisms than point mutations in small intestinal neuroendocrine tumors tumorigenesis.

Background Primary hyperparathyroidism is characterized by enlarged parathyroid glands due to an adenoma (80–85 %) or multiglandular disease (~15 %) causing hypersecretion of parathyroid hormone (PTH) and generally hypercalcemia. Parathyroid cancer is rare (

Background Small intestinal neuroendocrine tumors (SI-NETs) originate from the enterochromaffin cells in the ileum and jejunum. The knowledge about genetic and epigenetic abnormalities is limited. Low mRNA expression levels of actin gamma smooth muscle 2 (ACTG2) have been demonstrated in metastases relative to primary SI-NETs. ACTG2 and microRNA-145 (miR-145) are aberrantly expressed in other cancers and ACTG2 can be induced by miR-145. The aim of this study was to investigate the role of ACTG2 in small intestinal neuroendocrine tumorigenesis. Methods Protein expression was analyzed in SI-NETs (n = 24) and in enterochromaffin cells by immunohistochemistry. The cell line CNDT2.5 was treated with the histone methyltransferase inhibitor 3-deazaneplanocin A (DZNep), the selective EZH2 inhibitor EPZ-6438, or 5-aza-2’-deoxycytidine, a DNA hypomethylating agent. Cells were transfected with ACTG2 expression plasmid or miR-145. Western blotting analysis, quantitative RT-PCR, colony formation- and viability assays were performed. miR-145 expression levels were measured in tumors. Results Eight primary tumors and two lymph node metastases displayed variable levels of positive staining. Fourteen SI-NETs and normal enterochromaffin cells stained negatively. Overexpression of ACTG2 significantly inhibited CNDT2.5 cell growth. Treatment with DZNep or transfection with miR-145 induced ACTG2 expression (>10-fold), but no effects were detected after treatment with EPZ-6438 or 5-aza-2’-deoxycytidine. DZNep also induced miR-145 expression. SI-NETs expressed relatively low levels of miR-145, with reduced expression in metastases compared to primary tumors. Conclusions ACTG2 is expressed in a fraction of SI-NETs, can inhibit cell growth in vitro, and is positively regulated by miR-145. Theoretical therapeutic strategies based on these results are discussed. Electronic supplementary material The online version of this article (doi:10.1186/s12902-016-0100-3) contains supplementary material, which is available to authorized users.

The synthesis, structure and properties of two pentanuclear oxo-alkoxides are described. A combination of metathesis of LnCl(3) and 3KOPr(i) and stoichiometric hydrolysis resulted in the solvated o ...

Adsorption of trimethyl phosphate (TMP) on well-characterized hematite, maghemite and goethite nanopartides was studied by in situ DRIFT spectroscopy as a model system for adsorption of organophosphorous (OP) compounds on iron minerals. The iron minerals were characterized by X-ray diffraction (XRD), Raman spectroscopy, transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), specific surface area, and pore size distribution. The minerals were found to consist of stoichimetrically and morphologically well-defined maghemite, hematite, and goethite nanoparticles. Analysis of in situ diffuse reflectance Fourier transform (DRIFT) spectroscopy shows that TMP bonds mainly to Lewis acid Fe sites through the O phosphoryl atom (-P=O-Fe) on hematite and maghemite. On goethite most TMP molecules bond to Bronstedt acid surface OH groups and form hydrogen bonded surface complexes. The vibrational mode analysis and uptake kinetics suggest two main reasons for the observed trend of reactivity toward TMP (hematite > maghemite > goethite): (i) larger number of accessible Lewis acid adsorption sites on hematite; (ii) stronger interaction between the Lewis acid Fe sites and the phosphoryl O atom on TAP for hematite and maghemite compared to goethite with concomitant formation of surface coordinated TMP and dimethyl phosphate intermediates. As a result, on the oxides a surface oxidation pathway dominates during the initial adsorption, which results in the formation of surface methoxy and formate. In contrast, on goethite a slower hydrolysis pathway is identified, which eventually yields phosphoric acid. The observed trends of the reactivity and analysis of the corresponding surface structure and particle morphology suggest an intimate relation between the surface chemistry of exposed crystal facets on the iron minerals. These results are important to understand OP surface chemistry on iron minerals.

Primary hyperparathyroidism (pHPT) is a pathology associated with one or multiple hyperfunctioning parathyroid glands. The disease prevalence occurs in roughly 1-2% of the population primarily post-menopausal women. The molecular pathology of the disease is poorly understood. Elevated serum calcium levels in the setting of an inappropriately elevated parathyroid hormone level are indicative of the disease process. The ultimate treatment of the disease is to remove the hyperfunctioning gland.The aim of this thesis was to examine potential genetic and epigenetic aberrations that are potentially disease causing.The methylation signature of normal and pathological parathyroid tissue has yet to be investigated. DNA was bisulphite modified and analyzed using the Infinium HumanMethylation27 BeadChip. Distinct hierarchical clustering of genes with altered DNA methylation profiles in normal and pathologic parathyroid tissue was evident. DNA hypermethylation of CDKN2B, CDKN2A, WT1, SFRP1, SFRP2, and SFRP4 known to be important in the development of parathyroid tumors were associated with reduced gene expression in both benign and malignant parathyroid tumors.Familial primary hyperparathyroidism (FPHPT) may occur due to an underlying germ-line mutation in the MEN1, CASR, or HRPT2/CDC73 genes. Eighty-six young (≤45 years of age) patients with clinically non-syndromic PHPT underwent genetic analysis. Eight of 86 (9.3%) young patients with clinically non-familial PHPT displayed deleterious germ-line mutations in the susceptibility genes (4 MEN1, 3 CASR, and 1 HRPT2/ CDC73).Accumulation of non-phosphorylated active β -catenin has been reported to commonly occur in parathyroid adenomas from patients with primary hyperparathyroidism (pHPT). We assessed possible β-catenin stabilizing mutations in a large series of parathyroid adenomas. A total of one hundred and eighty sporadic parathyroid adenomas were examined for mutations in exon 3 of the CTNNB1gene. The mutation S33C (TCT >TGT) was detected by direct-DNA sequencing of PCR fragments in 1 out of 180 sporadic parathyroid adenomas (0.68 %).Eight matched tumor-constitutional DNA pairs from patients with sporadic parathyroid adenomas underwent whole-exome capture and high-throughput sequencing. Four of eight tumors displayed a frame shift deletion or nonsense mutations within the MEN1 gene, which was accompanied by loss of heterozygosity of the remaining wild-type allele. One tumor harbored a Y641N mutation of the histone methyltransferase EZH2 gene, previously linked to myeloid and lymphoid malignancy formation. Targeted sequencing in the additional 185 parathyroid adenomas revealed a high rate of MEN1 mutations (35%).

The genetic events leading the progression of midgut carcinoid tumors are largely unknown. The disease course varies from patient to patient, and there is a lack of reliable prognostic markers. In order to identify genes involved in tumor progression, gene expression profiling was performed on tumor specimens. Samples comprised 18 primary tumors, 17 lymph node (LN) metastases, and seven liver metastases from a total of 19 patients. Patients were grouped according to clinical data and histopathology into indolent or progressive course. RNA was subjected to a spotted oligo microarray and B-statistics were performed. Differentially expressed genes were verified using quantitative real-time PCR. Self-organizing maps demonstrated three clusters: 11 primary tumors separated in one cluster, five LN metastases in another cluster, whereas all seven liver metastases, seven primary, and 12 LN metastases formed a third cluster. There was no correlation between indolent and progressive behavior. The primary tumors with Ki67 >5%, with low frequency of the carcinoid syndrome, and a tendency toward shorter survival grouped together. Primary tumors differed in expression profile from their associated LN metastases; thus, there is evidence for genetic changes from primary tumors to metastases.ACTG2, GREM2, REG3A, TUSC2, RUNX1, TPH1, TGFBR2, andCDH6were differentially expressed between clusters and subgroups of tumors. The expression profile that assembles tumors as being genetically similar on the RNA expression level may not be concordant with the clinical disease course. This study reveals differences in gene expression profiles and novel genes that may be of importance in midgut carcinoid tumor progression.

Nickel-alumina/silica thin film materials for the use in solar thermal absorbers have been investigated using Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM) and Elastic Recoil Detection Analysis (ERDA). The TEM images revealed that all layers have a very small thickness variation and that the layers are completely homogenous. High resolution images showed 5–10 nm (poly) crystalline nickel nano-particles. ERDA showed that both the silica and alumina compositions contain more oxygen than 2:1 and 3:2 respectively. SEM showed the surface morphology and characteristics of the top silica anti-reflection layer. Hybrid-silica has showed to generate a smoother surface with less cracking compared to pure silica. The final curing temperature revealed to be of importance for the formation of cracks and the surface morphology.

Current studies suggest that short-term exposure of parathyroid glands to fibroblast growth factor 23 (FGF23) reduces parathyroid hormone secretion. However, patients with chronic kidney disease (CKD) develop secondary hyperparathyroidism despite high levels of serum FGF23, indicating a parathyroid FGF23 ‘resistance'. Here we analyzed the expression of the FGF23 receptors Klotho and FGF receptor 1 (FGFR1) in 88 hyperplastic parathyroid glands from 31 patients with CKD (including 21 renal allograft recipients), and their regulation in isolated bovine and human hyperplastic parathyroid cells. Glandular expression was variable, yet the Klotho and FGFR1 mRNA levels declined in parallel with the decreasing glomerular filtration rate, significantly decreasing over CKD stages. We found no association between the expression of Klotho, FGFR1, and the proliferation marker Ki67. In vitro treatment of bovine cells with FGF23 or calcium reduced the Klotho level, whereas active vitamin D 3 compounds increased its expression. Phosphate and parathyroid hormone had no effect. Treatment had less impact on Klotho in cultured human cells than in the bovine healthy cell model, whereas FGFR1 expression was induced in the hyperplastic cells. Thus parathyroid Klotho and FGFR1 decrease with declining renal function, possibly because of alterations in mineral metabolism related to the failing kidney. This could explain the observed parathyroid resistance to FGF23 in late CKD.

The mechanism behind Ca2+ entry into the parathyroid cells has been widely debated, and the molecular identities of the responsible ion channels have not been established yet. In this study, we show that the parathyroid cells lack voltage-operated Ca2+ channels. Passive store depletion by thapsigargin, on the other hand, induces a large non-voltage-activated non-selective cation current. The increase in intracellular Ca2+ caused by thapsigargin is attenuated by 2-aminoethoxydiphenyl borate, a blocker of store-operated Ca2+ entry (SOCE). Candidate molecules for non-voltage-operated Ca2+ signaling were investigated. These included members of the transient receptor potential canonical (TRPC) ion channel family, as well as Ca2+ release-activated Ca2+ modulator 1 (Orai1) and stromal interaction molecule 1 (STIM1) that are key proteins in the SOCE pathway. Using RT-PCR screening, quantitative real-time PCR, and western blot, we showed expression of TRPC1, TRPC4, and TRPC6; Orai1; and STIM1 genes and proteins in normal and adenomatous human parathyroid tissues. Furthermore, co-immunoprecipitation experiments demonstrated a ternary complex of TRPC1–Orai1–STIM1, supporting a physical interaction between these molecules in human parathyroid.

Pheochromocytomas of the adrenal medulla may be life-threatening catecholamine-producing tumors which are malignant in about 10% of cases. Differential diagnosis between malignant and benign tumors is dependent on the development of metastasis or extensive local invasion. A number of genetic aberrations have been described in pheochromocytomas, but no marker associated to malignancy has been reported. We applied an expression microarray containing 7770 cDNA clones and analysed the expression profiles in eleven tumors compared to normal adrenal medulla. Stathmin (STMN1, Op18) was most conspiciously overexpressed among the differentially expressed genes. RT-PCR analysis further confirmed mRNA overexpression, 6 to 8-fold for benign and malignant tumors, and 16-fold for metastases. Stathmin protein overexpression was observed by immunohistochemistry, and distinct differential protein expression between benign and malignant/metastasis specimens was confirmed by Western blot analysis. The results introduce stathmin as a possible diagnostic marker for malignant pheochromocytomas, and further evaluations are warranted.

Primary hyperparathyroidism (HPT) is often caused by a benign parathyroid tumor, adenoma; less commonly by multiglandular parathyroid disease/hyperplasia; and rarely by parathyroid carcinoma. Patients with multiple tumors require wider exploration to avoid recurrence and have increased risk for hereditary disease. Secondary HPT is a common complication of renal failure. Improved knowledge of the molecular background of parathyroid tumor development may help select patients for appropriate surgical treatment and can eventually provide new means of treatment. The present contribution summarizes more recent knowledge of parathyroid molecular genetics.A literature search and review was made to evaluate the level of evidence concerning molecular biology and genetics of primary, secondary, and familial HPT according to criteria proposed by Sackett, with recommendation grading by Heinrich et al.Most parathyroid adenomas and hyperplastic glands are monoclonal lesions. Cyclin D1 gene (CCND1) translocation and oncogene action occur in 8% of adenomas; cyclin D1 overexpression is seen in 20% to 40% of parathyroid adenomas and in 31% of secondary hyperplastic glands. Somatic loss of one MEN1 allele is seen in 25% to 40% of sporadic parathyroid adenomas, half of which have inactivating mutation of the remaining allele. Inactivating somatic HRPT2 mutations are common in parathyroid carcinoma, often causing decreased expression of the protein parafibromin involved in cyclin D1 regulation. Aberrant regulation of Wnt/beta-catenin signaling may be important for parathyroid tumor development.Molecular genetic studies of parathyroid tumors are well designed basic experimental studies providing strong level III evidence, with data frequently confirmed by subsequent studies.

We report on the photoinduced decomposition of acetone on Zr- and Nb-doped anatase TiO2 nanoparticles prepared by the sol−gel method in oxygen-free environment (N2) and synthetic air, respectively. Physical properties of the nanoparticles were determined by TEM, SEM, AFM, XRD, and UV−vis spectroscopy. Photoinduced surface reactions were monitored by in situ Fourier transform infrared (FTIR) spectroscopy. Acetone photo-oxidation occurs in the absence of O2 in the reaction gas and is proposed to be due to reactions with photoactivated surface oxygen. In N2 atmosphere a new parallel reaction pathway is found that stimulates surface carbonate formation. A coupled diffusion-reaction model was developed to quantitatively determine the role of O diffusion. The results yield quantitative support to an oxygen surface diffusion mechanism, which depletes the surface from oxygen and gradually deactivates the particles in the absence of external oxygen supply. The diffusion reaction pathway is significant on the doped...

Context: The type I membrane protein Klotho was recently shown to mediate PTH secretion in parathyroid cells in response to low extracellular calcium. In contrast, Klotho inhibits PTH secretion indirectly through the action of fibroblast growth factor-23. Abnormal Klotho expression in parathyroid disorders remains to be elucidated. Objective: The aim of the study was to determine: 1) Klotho expression in parathyroid adenomas from patients with primary hyperparathyroidism (pHPT) compared to normal tissue; and 2) its relation to the serum calcium and PTH levels. Design: Surgically removed parathyroid glands (n = 40) and four normal parathyroid tissue specimens were analyzed for Klotho mRNA and protein levels by quantitative real-time PCR and immunohistochemistry. In vitro effects of calcium on Klotho mRNA expression were studied in bovine parathyroid cells. Results: Klotho mRNA levels were significantly decreased (n = 23) or undetectable (n = 17) in parathyroid adenomas compared to normal tissues (P < 0.001). Reduced Klotho protein expression was confirmed by immunohistochemistry. Klotho mRNA levels were inversely correlated to serum calcium (r = −0.97; P < 0.0001), and calcium dose-dependently decreased Klotho mRNA expression in normal parathyroid cells in vitro (P < 0.01). Serum calcium was the only significant marker of Klotho expression in multivariate analysis with calcium, phosphate, PTH, and adenoma weight as independent variables. Conclusions: Parathyroid Klotho expression is decreased or undetectable in pHPT. We provide evidence that 1) serum calcium is strongly associated with parathyroid Klotho expression in pHPT; and 2) abnormal PTH secretion in hypercalcemic pHPT subjects is mediated by Klotho-independent mechanisms.

Thin film materials for the use in solar thermal absorbers have been investigated using time-of-flight energy elastic recoil detection analysis (ERDA). The ERDA measurements proved to be very effic ...