Quantitative screening of an extended oxidative coupling of methane catalyst library

A comprehensive microkinetic model, including catalyst descriptors, that accounts for the homogeneous as well as heterogeneously catalyzed reaction steps in Oxidative Coupling of Methane (OCM) was used in the assessment of large kinetic datasets acquired on five different catalytic materials. The applicability of the model was extended from alkali magnesia catalysts represented by Li/MgO and Sn-Li/MgO and alkaline earth lanthana catalysts represented by Sr/La2O3 to rare earth-promoted alkaline earth calcium oxide catalysts, represented by LaSr/CaO, and to a Na-Mn-W/SiO2 catalyst. The model succeeded in adequately simulating the performance of all five investigated catalysts in terms of reactant conversion and product selectivities in the entire range of experimental conditions. It was found that the activity of Sr/La2O3, in terms of methane conversion, is approximately 2, 5, 30 and 33 times higher than over the La-Sr/CaO, Sn-Li/MgO, Na-Mn-W/SiO2 and Li/MgO catalysts, respectively, under identical operating conditions. This was attributed mainly to the high stability of adsorbed hydroxyls, the high stability of adsorbed oxygen and the high concentration of active sites of Sr/La2O3. The selectivity towards C2 products was found to depend on the methyl radical sticking coefficient and the stability of the adsorbed oxygen and was the highest on the Na-W-Mn/SiO2 catalyst, that is 75% at about 1% methane conversion and 1023 K, 190 kPa and inlet molar CH4/O2 ratio of 4

TLR3 expression induces apoptosis in human non‐small‐cell lung cancer

The prognostic value of Toll\u2010like receptor 3 (TLR3) is debated in cancer, differing between tumor types, methods, and cell types. We recently showed for the first time that TLR3 expression on early stage non\u2010small\u2010cell lung cancer (NSCLC) results associated with a good prognosis. Here, we provide experimental evidences explaining the molecular reason behind TLR3\u2019s favorable prognostic role. We demonstrated that TLR3 activation in vitro induces apoptosis in lung cancer cell lines and, accordingly, that TLR3 expression is associated with caspase\u20103 activation in adenocarcinoma NSCLC specimens, both evaluated by immunohistochemistry. Moreover, we showed that TLR3 expression on cancer cells contributes to activate the CD103+ lung dendritic cell subset, that is specifically associated with processing of antigens derived from apoptotic cells and their presentation to CD8+ T lymphocytes. These findings point to the relevant role of TLR3 expression on lung cancer cells and support the use of TLR3 agonists in NSCLC patients to re\u2010activate local innate immune response

Ekspresija i obrada somatostatina u gušterači u razvoju i u duktalnom adenokarcinomu gušterače

Somatostatin is a gastrointestinal peptide hormone that inhibits growth of pancreatic cancer as reported by an increasing body of evidence. Yet this is not always the case. To clarify the controversy we aimed to identify the expression of somatostatin in developing human embryonic pancreatic tissue and pancreatic adenocarcinoma given that somatostatin positive cells were shown either into primitive pancreatic ductal epithelium or into pancreatic carcinoma. Tissue sections representing pancreatic fetal specimens (n=15) and ductal pancreatic adenocarcinoma specimens (n=15) were assessed using immunohistochemical methods for somatostatin expression. Normal primitive exocrine ductal epithelium and endocrine epithelium showed a definite, statistically significant, higher expression of somatostatin over neoplastic pancreatic tissue of mixed (ductal-endocrine) and pure ductal type (p1=0.021, p2=0.001, p3<0.0001and p4=0.003 respectively) during the 8th to the 10th week. No statistically significantly different expression of somatostatin in the mantle zone of the islets over neoplastic tissue of mixed (p5=0.16) and pureductal type (p6=0.65), from the 13th to the 24th week was demonstrated. Pancreatic cancer cells can express somatostatin in a model that reproduces the normal expression of the peptide by d-cells during embryonal organogenesis. Therapy aimed at pancreatic cancer must be targeted to somatostatin and analogues as a potential adjuvant novel option.Somatostatin je probavni peptidni hormon koji suzbija rast raka gušterače, za što postoji sve više dokaza. No to se ne događa uvijek. Cilj studije bio je utvrditi ekspresiju somatostatina u ljudskom embrijskom tkivu gušterače u razvoju i u adenokarcinomu gušterače, s tim da su na somatostatin pozitivne stanice dokazane ili u primitivnom duktalnom epitelu gušterače ili u karcinomu gušterače. Tkivni isječci koji su predstavljali uzorke fetalne gušterače (n=15) i uzorke adenokarcinoma gušterače (n=15) ispitani su pomoću imunohistokemijskih metoda za ekspresiju somatostatina. Normalan primitivni egzokrini duktalni epitel i endokrini epitel pokazao je konačnu, statistički značajno višu ekspresiju somatostatina iznad neoplastičnog tkiva gušterače miješanog (duktalno-endokrinog) i čistog duktalnog tipa (p1=0,021, P2=0,001, p3<0,0001 odnosno p4=0,003) tijekom 8. do 10. tjedna. Nije dokazana statistički značajno različita ekspresija somatostatina u ovojnom sloju (mantle zone, mantle layer) otočića iznadneoplastičnog tkiva miješanog (p5=0,16) i čistog duktalnog tipa (p6=0,65) od 13. do 24. tjedna. Dakle, stanice raka gušterače mogu izražavati somatostatin na naein koji ponavlja normalnu d-staničnu ekspresiju peptida za vrijeme embrijske organogeneze. Liječenje zbog raka gušterače usmjereno na somatostatin i njegove analoge moglo bi predstavljati novu mogućnosti adjuvantne terapije

Toll-like receptor 3 as a new marker to detect high risk early stage Non-Small-Cell Lung Cancer patients

Immune and epithelial cells express TLR3, a receptor deputed to respond to microbial signals activating the immune response. The prognostic value of TLR3 in cancer is debated and no data are currently available in NSCLC, for which therapeutic approaches that target the immune system are providing encouraging results. Dissecting the lung immune microenvironment could provide new prognostic markers, especially for early stage NSCLC for which surgery is the only treatment option. In this study we investigated the expression and the prognostic value of TLR3 on both tumor and immune compartments of stage I NSCLCs. In a cohort of 194 NSCLC stage I, TLR3 immunohistochemistry expression on tumor cells predicted a favorable outcome of early stage NSCLC, whereas on the immune cells infiltrating the tumor stroma, TLR3 expression associated with a poor overall survival. Patients with TLR3-positive immune infiltrating cells, but not tumor cells showed a worse prognosis compared with all other patients. The majority of TLR3-expressing immune cells resulted to be macrophages and TLR3 expression associates with PD-1 expression. TLR3 has an opposite prognostic significance when expressed on tumor or immune cells in early stage NCSCL. Analysis of TLR3 in tumor and immune cells can help in identifying high risk stage I patients for which adjuvant treatment would be beneficial

Diffuse large B-cell lymphoma arising from a multicentric mixed variant of Castleman's disease

This case report describes a patient with multicentric mixed type Castleman\u2032s disease and concomitant non-Hodgkin\u2032s lymphoma of diffuse large B cell type in the neck. Multicentric CD is a systemic illness with disseminated lymphadenopathy; its aggressive and usually fatal course is associated with infectious complications and risk for malignant tumors, such as lymphoma or Kaposi sarcoma

Reduction of nucleosome assembly during new DNA synthesis impairs both major pathways of double-strand break repair

Assembly of new chromatin during S phase requires the histone chaperone complexes CAF-1 (Cac2p, Msi1p and Rlf2p) and RCAF (Asf1p plus acetylated histones H3 and H4). Cells lacking CAF-1 and RCAF are hypersensitive to DNA-damaging agents, such as methyl methanesulfonate and camptothecin, suggesting a possible defect in double-strand break (DSB) repair. Assays developed to quantitate repair of defined, cohesive-ended break structures revealed that DSB-induced plasmid:chromosome recombination was reduced ∼10-fold in RCAF/CAF-1 double mutants. Recombination defects were similar with both chromosomal and plasmid targets in vivo, suggesting that inhibitory chromatin structures were not involved. Consistent with these observations, ionizing radiation-induced loss of heterozygosity was abolished in the mutants. Nonhomologous end-joining (NHEJ) repair proficiency and accuracy were intermediate between wild-type levels and those of NHEJ-deficient yku70 and rad50 mutants. The defects in NHEJ, but not homologous recombination, could be rescued by deletion of HMR-a1, a component of the a1/alpha2 transcriptional repressor complex. The findings are consistent with the observation that silent mating loci are partially derepressed. These results demonstrate that defective assembly of nucleosomes during new DNA synthesis compromises each of the known pathways of DSB repair and that the effects can be indirect consequences of changes in silenced chromatin structure

Modeling on fluid flow and inclusion motion in centrifugal continuous casting strands

During the centrifugal continuous casting process, unreasonable casting parameters can cause violent level fluctuation, serious gas entrainment, and formation of frozen shell pieces at the meniscus. Thus, in the current study, a three-dimensional multiphase turbulent model was established to study the transport phenomena during centrifugal continuous casting process. The effects of nozzle position, casting and rotational speed on the flow pattern, centrifugal force acting on the molten steel, level fluctuation, gas entrainment, shear stress on mold wall, and motion of inclusions during centrifugal continuous casting process were investigated. Volume of Fluid model was used to simulate the molten steel-air two-phase. The level fluctuation and the gas entrainment during casting were calculated by user-developed subroutines. The trajectory of inclusions in the rotating system was calculated using the Lagrangian approach. The results show that during centrifugal continuous casting, a large amount of gas was entrained into the molten steel, and broken into bubbles of various sizes. The greater the distance to the mold wall, the smaller the centrifugal force. Rotation speed had the most important influence on the centrifugal force distribution at the side region. Angular moving angle of the nozzle with 8° and keeping the rotation speed with 60 revolutions per minute can somehow stabilize the level fluctuation. The increase of angular angle of nozzle from 8 to 18 deg and rotation speed from 40 to 80 revolutions per minute favored to decrease the total volume of entrained bubbles, while the increase of distance of nozzle moving left and casting speed had reverse effects. The trajectories of inclusions in the mold were irregular, and then rotated along the strand length. After penetrating a certain distance, the inclusions gradually moved to the center of billet and gathered there. More work, such as the heat transfer, the solidification, and the inclusions entrapment during centrifugal continuous casting, will be performed

Remodeling of the chromatin structure of the facioscapulohumeral muscular dystrophy (FSHD) locus and upregulation of FSHD-related gene 1 (FRG1) expression during human myogenic differentiation

<p>Abstract</p> <p>Background</p> <p>Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant neuromuscular disorder associated with the partial deletion of integral numbers of 3.3 kb D4Z4 DNA repeats within the subtelomere of chromosome 4q. A number of candidate FSHD genes, adenine nucleotide translocator 1 gene (<it>ANT1</it>), FSHD-related gene 1 (<it>FRG1</it>), <it>FRG2 </it>and <it>DUX4c</it>, upstream of the D4Z4 array (FSHD locus), and double homeobox chromosome 4 (<it>DUX4</it>) within the repeat itself, are upregulated in some patients, thus suggesting an underlying perturbation of the chromatin structure. Furthermore, a mouse model overexpressing <it>FRG1 </it>has been generated, displaying skeletal muscle defects.</p> <p>Results</p> <p>In the context of myogenic differentiation, we compared the chromatin structure and tridimensional interaction of the D4Z4 array and <it>FRG1 </it>gene promoter, and <it>FRG1 </it>expression, in control and FSHD cells. The <it>FRG1 </it>gene was prematurely expressed during FSHD myoblast differentiation, thus suggesting that the number of D4Z4 repeats in the array may affect the correct timing of <it>FRG1 </it>expression. Using chromosome conformation capture (3C) technology, we revealed that the <it>FRG1 </it>promoter and D4Z4 array physically interacted. Furthermore, this chromatin structure underwent dynamic changes during myogenic differentiation that led to the loosening of the <it>FRG1</it>/4q-D4Z4 array loop in myotubes. The <it>FRG1 </it>promoter in both normal and FSHD myoblasts was characterized by H3K27 trimethylation and Polycomb repressor complex binding, but these repression signs were replaced by H3K4 trimethylation during differentiation. The D4Z4 sequences behaved similarly, with H3K27 trimethylation and Polycomb binding being lost upon myogenic differentiation.</p> <p>Conclusion</p> <p>We propose a model in which the D4Z4 array may play a critical chromatin function as an orchestrator of <it>in cis </it>chromatin loops, thus suggesting that this repeat may play a role in coordinating gene expression.</p