Journal articles: 'DMDA' – Grafiati (2024)

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Abstract Abstract 2437 Background: Acute myeloid leukemia (AML) remains a devastating disease. This is mainly due to limited treatment options for patients with relapsed or refractory disease and those with FMS-like tyrosine kinase 3 (FLT3) internal tandem duplication (ITD) mutations. FLT3-ITD occurs in approximately a quarter of patients with AML and confers poor prognosis due to high propensity for relapse after remission. The discovery of novel therapies is necessary for cure of AML. Pateamine A (Pat A) is a natural protein translation inhibitor that targets the eukaryotic initiation factor 4A (eIF4A) and inhibits 5'CAP dependent translation. A previous study by Galina Kuznetsov revealed that des-methyl, des-amino Pateamine A (DMDA-Pat A), a synthetic analogue of Pat A, had potent anti-proliferative activity against several human cancer cell lines, including melanoma, colon cancer, non-small cell lung cancer and pre-B acute lymphoid leukemia (Molecular Cancer Therapeutics 2009). The effectiveness of Pat A on AML cells has yet to be elucidated. The primary objective of this study was to determine if Pat A decreased AML FLT3-ITD cell proliferation and caused cell death. The secondary objective was to determine if Pat A decreased AML FLT3-ITD cell protein translation. Lastly, the tertiary objectives were to compare Pat A to AML therapies currently under investigation and in clinical practice and to examine the effects of combination treatments with Pat A on AML FLT3-ITD cells. Methods: Human acute myeloid leukemia MV411 (FLT3-ITD) cells were seeded in the presence of increasing concentrations of DMDA-Pat A. After 48 hours cell proliferation was assessed using MTS assay. To determine if MV411 cells underwent cell death, western blot analysis for PARP-cleavage and fluorometric caspase activation analysis were performed on cell lysates after DMDA -Pat A treatment for 24 hours. Western blot analysis for cell survival regulatory proteins, XIAP, MCL-1, BCL2 and BCL-XL, were performed on treated cell lysates as well. To determine if DMDA-Pat A decreased MV411 protein translation, cells were treated for 3 hours with DMDA-Pat A and labeled with 35S-methionine during last 15 minutes of experiment. Radiolabeled proteins were trichloroacetic acid (TCA) precipitated and measured by scintillation counting. In order to compare DMDA-Pat A to compounds currently in clinical practice, MTS cell proliferation assays were performed on MV411 cells with increasing concentrations of Idarubicin, Cytarabine and Midostaurin (PKC 412; FLT3 inhibitor). Also DMDA-Pat A was compared to Torin, a mammalian target of rapamycin complex (mTORC1/2) inhibitor, which is currently under investigation for treatment of AML. Lastly, MV411 cells were treated with DMDA-Pat A in combination with the above compounds in order to possibly produce synergistic inhibition of cell growth. Results: DMDA-Pat A decreased MV411 cell proliferation with an IC50 of approximately 20 nM. The maximum inhibition of cell growth was achieved at 100nM of DMDA-Pat A. Western blot analyses revealed that MV411 cells underwent cell death as determined by PARP cleavage with 20nM and 100nM of DMDA-Pat A. Fluorometric caspase activation assay revealed an increase in caspase activation with 20nM DMDA-Pat A treatment. Cell survival regulatory proteins XIAP, MCL-1 and BCL-XL were all decreased whereas BCL-2 was unchanged. In comparison to control, MV411 protein translation was decreased by 50% after 20 nM DMDA-Pat A treatment. Idarubicin, Cytarabine, Midostaurin and Torin were all able to decrease MV411 cell proliferation, but the half maximal inhibitory concentrations (IC50) of all four compounds were greater than DMDA-Pat A (Idarubicin IC50 100nm, Cytarabine IC50 30nm, Midostaurin IC50 125nm and Torin IC50 60 nm). Lastly, there was no synergistic inhibition of cell growth with DMDA-Pat A and any of the above four compounds, but DMDA-Pat A in combination with Idarubicin produced additive inhibition of cell growth. Conclusion: DMDA-Pat A decreases proliferation of FLT3-ITD MV411 cells by reducing cell survival proteins and inducing apoptosis at low concentrations. DMDA-Pat A was determined to be effective at concentrations lower than another protein synthesis inhibitor (Torin) or other cytotoxic agents (Idarubicin, Cytarabine, Midostaurin). In combination with other cytotoxic drugs, DMDA-Pat A could be a potential treatment option for AML patients with FLT3-ITD mutations. Disclosures: No relevant conflicts of interest to declare.

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Dimethylsulfoniopropionate (DMSP), an osmolyte produced by oceanic phytoplankton and bacteria, is primarily degraded by bacteria belonging to the Roseobacter lineage and other marine Alphaproteobacteria via DMSP-dependent demethylase A protein (DmdA). To date, the evolutionary history of DmdA gene family is unclear. Some studies indicate a common ancestry between DmdA and GcvT gene families and a co-evolution between Roseobacter and the DMSP-producing-phytoplankton around 250 million years ago (Mya). In this work, we analyzed the evolution of DmdA under three possible evolutionary scenarios: (1) a recent common ancestor of DmdA and GcvT, (2) a coevolution between Roseobacter and the DMSP-producing-phytoplankton, and (3) an enzymatic adaptation for utilizing DMSP in marine bacteria prior to Roseobacter origin. Our analyses indicate that DmdA is a new gene family originated from GcvT genes by duplication and functional divergence driven by positive selection before a coevolution between Roseobacter and phytoplankton. Our data suggest that Roseobacter acquired dmdA by horizontal gene transfer prior to an environment with higher DMSP. Here, we propose that the ancestor that carried the DMSP demethylation pathway genes evolved in the Archean, and was exposed to a higher concentration of DMSP in a sulfur-rich atmosphere and anoxic ocean, compared to recent Roseobacter eco-orthologs (orthologs performing the same function under different conditions), which should be adapted to lower concentrations of DMSP.

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ABSTRACT In silico design and testing of environmental primer pairs with metagenomic data are beneficial for capturing a greater proportion of the natural sequence heterogeneity in microbial functional genes, as well as for understanding limitations of existing primer sets that were designed from more restricted sequence data. PCR primer pairs targeting 10 environmental clades and subclades of the dimethylsulfoniopropionate (DMSP) demethylase protein, DmdA, were designed using an iterative bioinformatic approach that took advantage of thousands of dmdA sequences captured in marine metagenomic data sets. Using the bioinformatically optimized primers, dmdA genes were amplified from composite free-living coastal bacterioplankton DNA (from 38 samples over 5 years and two locations) and sequenced using 454 technology. An average of 6,400 amplicons per primer pair represented more than 700 clusters of environmental dmdA sequences across all primers, with clusters defined conservatively at >90% nucleotide sequence identity (∼95% amino acid identity). Degenerate and inosine-based primers did not perform better than specific primer pairs in determining dmdA richness and sometimes captured a lower degree of richness of sequences from the same DNA sample. A comparison of dmdA sequences in free-living versus particle-associated bacteria in southeastern U.S. coastal waters showed that sequence richness in some dmdA subgroups differed significantly between size fractions, though most gene clusters were shared (52 to 91%) and most sequences were affiliated with the shared clusters (∼90%). The availability of metagenomic sequence data has significantly enhanced the design of quantitative PCR primer pairs for this key functional gene, providing robust access to the capabilities and activities of DMSP demethylating bacteria in situ.

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Environmental context Corals produce copious amounts of dimethylsulfoniopropionate (DMSP), a sulfur compound implicated in climate regulation. We studied DMSP concentrations inside corals and unveiled the linkage between DMSP availability and the abundance of DMSP-degrading bacterial groups inhabiting the corals’ surface. Our findings suggest that DMSP mediates the interplay between corals and microbes, highlighting the importance of sulfur compounds for microbial processes in corals and for the resilience of coral reef ecosystems. Abstract Corals produce copious amounts of dimethylsulfoniopropionate (DMSP), a sulfur compound thought to play a role in structuring coral-associated bacterial communities. We tested the hypothesis that a linkage exists between DMSP availability in coral tissues and the community dynamics of bacteria in coral surface mucus. We determined DMSP concentrations in three coral species (Meandrina meandrites, Porites astreoides and Siderastrea siderea) at two sampling depths (5 and 25m) and times of day (dawn and noon) at Curaçao, Southern Caribbean. DMSP concentration (4–409nmolcm–2 coral surface) varied with host species-specific traits such as Symbiodinium cell abundance, but not with depth or time of sampling. Exposure of corals to air caused a doubling of their DMSP concentration. The phylogenetic affiliation of mucus-associated bacteria was examined by clone libraries targeting three main subclades of the bacterial DMSP demethylase gene (dmdA). dmdA gene abundance was determined by quantitative Polymerase Chain Reaction (qPCR) against a reference housekeeping gene (recA). Overall, a higher availability of DMSP corresponded to a lower relative abundance of the dmdA gene, but this pattern was not uniform across all host species or bacterial dmdA subclades, suggesting the existence of distinct DMSP microbial niches or varying dmdA DMSP affinities. This is the first study quantifying dmdA gene abundance in corals and linking related changes in the community dynamics of DMSP-degrading bacteria to DMSP availability. Our study suggests that DMSP mediates the regulation of microbes by the coral host and highlights the significance of sulfur compounds for microbial processes in coral reefs.

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Green concrete is a concrete that supports the content of CO2 emissions reductions by using waste industries as cement replacement. The waste industries that commonly can be used in green concrete mixture design are fly ash, blast furnace slag, silica fume, and rice husk ash. The present of supplementary cementitous material in green concrete mixture can increase both compressive strength and cement efficiency. The higher of cement efficiency, the higher compressive strength and the lower cement content will be. Densified Mixture Design Algorithm (DMDA) is a method that has been widely applied to concrete constructions in Taiwan. DMDA method can support the higher of cement efficiency in green concrete design. By using DMDA to create green concrete with supplementary cementitous material can increase the life of concrete and hence reduce life-cycle cost.

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This study is mainly to investigate the early age cracking due to the addition of silica fume (SF) into concrete and to propose Densified Mixture Design Algorithm (DMDA) method as a trouble-shooting strategy. Specimens with different water-to-binder ratio (W/B) and silica fume content were prepared with ACI concrete (W/B = 0.23, 0.35 and 0.47; SF content = 0%, 10%, 20% and 30%) and DMDA concrete (W/B = 0.23, 0.35 and 0.47; coating paste thickness t = 5, 15 and 25 μm). Adding silica fume to the concrete system to replace part of cement may increase the crack intensity, and the rate of water absorption; but reduce the heat of hydration. DMDA method as a problem-shooting technique shows to have a better performance in reducing the crack intensities up to 41% with W/B = 0.23 and the better durability index than that of ACI method.

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The present study evaluates the mechanical-microstructural characteristics of the densified high-performance concrete (HPC) incorporating high volume fly ash (FA). The densified mixture design algorithm (DMDA) technology was applied to design the concrete proportions. The effects of various FA contents on both fresh and hardened concrete were investigated. A scanning electron microscope (SEM) was used to observe the microstructure of the concrete samples. The effectiveness of using DMDA in mix deign was also discussed in this study. As the experimental results, the FA content was found to affect the concrete properties significantly. The maximum compressive strength value of 65.1 MPa was obtained at the concrete samples containing 40% FA. Additionally, the 40% FA samples exhibited a denser microstructure as compared to the others. Generally, all of the tested concrete samples exhibited good performance in terms of workability, strength development, water absorption, and porosity. The results of this study further show the effectiveness of using DMDA technology in proportioning of the concrete mixture.

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ABSTRACT The ubiquitous algal metabolite dimethylsulfoniopropionate (DMSP) is a major source of carbon and reduced sulfur for marine bacteria. Recently, the enzyme responsible for the demethylation of DMSP, designated DmdA, was identified, and homologs were found to be common in marine bacterioplankton cells. The recombinant DmdA proteins from the cultured marine bacteria Pelagibacter ubique HTCC1062 and Silicibacter pomeroyi DSS-3 were purified with a three-step procedure using anion-exchange, hydrophobic interaction, and hydroxyapatite chromatographies. The P. ubique enzyme possessed an M r on sodium dodecyl sulfate-polyacrylamide gel electrophoresis of 38,500. Under nondenaturing conditions, the M r was 68,000, suggesting that the enzyme was likely to be a dimer. The purified enzyme exhibited strict substrate specificity for DMSP, as DmdA from both S. pomeroyi and P. ubique possessed no detectable demethylase activity with glycine betaine, dimethyl glycine, methylmercaptopropionate, methionine, or dimethylsulfonioacetate. Less than 1% activity was found with dimethylsulfoniobutanoate and dimethylsulfoniopentanoate. The apparent Km s for DMSP were 13.2 ± 2.0 and 5.4 ± 2.3 mM for the P. ubique and S. pomeroyi enzymes, respectively. In cell extracts of S. pomeroyi DSS-3, the apparent Km for DMSP was 8.6 ± 1.2 mM, similar to that of purified recombinant DmdA. The intracellular concentration of DMSP in chemostat-grown S. pomeroyi DSS-3 was 70 mM. These results suggest that marine bacterioplankton may actively accumulate DMSP to osmotically significant concentrations that favor near-maximal rates of DMSP demethylation activity.

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Waste materials are defined as all unwanted substances from manufacturing processes, including mining, industry, agriculture and others. One of the most commonly used waste product in concrete manufacturing is Fly Ash (FA). Studies have shown that the content of Fly Ash increases the workability of concrete, being useful in production of Self-Consolidating Concretes (SCC). One of the designing methods involving high amounts of fly ash is based on the Densified Mixture Design Algorithm (DMDA). This article attempts to work out HWSCC manufacturing method using the DMDA method with the use of barite and magnetite aggregates. The study integrates six concrete mixes. Concrete strength was tested on 10x10x10 cm samples after 3,7 and 28 days. The rheological properties were tested with Slump Test to find out if the mixes exhibit self-consolidating properties. Concretes with magnetite aggregate exhibit higher strength than concretes with barite aggregate. The study has shown that the DMDA method, designed to produce durable, low-cement concrete may not be applicable in the case of crushed aggregates. The study has shown that the method allows to decrease the cement amount and re-place it with pozzolan waste product to acquire concretes with similar properties to the ones acquired using different methods.

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Background:Isocyanates are mainly considered respiratory allergens but can also cause contact allergy. Diphenylmethane-4,4′-diamine (4,4′-MDA) has been considered a marker for diphenylmethane-4,4′-diisocyanate (4,4′-MDI) contact allergy. Furthermore, overrepresentation of positive patch-test reactions top-phenylenediamine (PPD) in 4,4′-MDA positive patients have been reported.Objectives:To investigate the sensitizing capacities of toluene-2,4-diisocyanate (2,4-TDI) and PPD and the cross-reactivity of 4,4′-MDA, 2,4-TDI, dicyclohexylmethane-4,4′-diamine (4,4′-DMDA), dicyclohexylmethane-4,4′-diisocyanate (4,4′-DMDI), 4,4′-MDI and PPD.Methods:The Guinea Pig Maximization Test (GPMT) was used.Results:PPD was shown to be a strong sensitizer (p<0.001). Animals sensitized to PPD showed cross-reactivity to 4,4′-MDA (p<0.001). Animals sensitized to 4,4′-MDA did not show cross-reactivity to PPD. 8 animals sensitized to 2,4-TDI were sacrificed due to toxic reactions at the induction site and could thus not be fully evaluated.Conclusion:PPD was shown to be a strong sensitizer. However, it cannot be used as a marker for isocyanate contact allergy. On the other hand, positive reactions to 4,4′-MDA could indicate a PPD allergy. The intradermal induction concentration of 2,4-TDI (0.70% w/v) can induce strong local toxic reactions in guinea-pigs and should be lowered.

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It is not difficult to prepare self-compacting concrete (SCC) in laboratory now. The problem researchers faced is how SCC can be popularized in civil engineering. A modified densification mixture design algorithm (DMDA) is used in this study to prepare the control mixture. And on the basis of the system analysis for exist studies, 6 factors are chosen as experimental factor and 25 experiments are designed by orthogonal design experiment method. The results analysis indicates that only 3 factors are significant on SCC and their recommend value is obtained respectively. It may shed light on the application of SCC.

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SummaryProliferation of fibroblasts is vital for adequate wound healing but is probably also involved in different hyperproliferative disorders such as atherosclerosis and cancer. The regeneration of tissue usually starts with coagulation, involving release of mitogenic and inflammatory factors from activated platelets. This study focuses on the role of eicosanoids in the proliferative effects of platelets on human fibroblasts. We show that the phospholipase A2 inhibitor 7,7-dimethyl-5,8-eicosadienoic acid (DMDA), the combined cyclooxygenase (COX) and lipoxygenase (LOX) inhibitor 5,8,11,14-eicosatetraynoic acid (ETYA) and the LOX inhibitor 5,8,11-eicosatriynoic acid (ETI) block the platelet-induced proliferation of serum starved subconfluent human fibroblasts. Anti-proliferative effects were also obtained by specific inhibition of 5-LOX with 5,6-dehydro arachidonic acid (5,6-dAA), whereas the 12-LOX inhibitor cinnamyl-3,4-dihydroxy-α-cyanocinnamate (CDC) did not affect the platelet-stimulated growth of fibroblasts. The expression of 5-LOX was analyzed by reverse-transcriptase-mediated PCR (RT-PCR), Western blotting and HPLC. 5-LOX message and protein was detected in fibroblasts but not in platelets. Incubation with platelets markedly increased, already after one hour, the expression of 5-LOX in the fibroblast culture. The increased 5-LOX activity was associated with an elevated level of the 5-LOX metabolite 5-hydroxyeicosatetraenoic acid (5-HETE) reaching its maximum after 1–2 hours of co-incubation of fibroblasts and platelets. The 5-HETE production was reduced by the inhibitors DMDA, ETYA and ETI. In conclusion, this study suggests that platelet-stimulated proliferation of fibroblasts is mediated by an increased 5-LOX activity, which supports recent findings indicating a crucial role for this enzyme in proliferative disorders such as atherosclerosis.

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New pyrimidine deoxyribonucleoside analogues, 2′-deoxy-2′-methylideneuridine (DMDU), 2′-deoxy-2′-methylidenecytidine (DMDC), and their 5-substituted derivatives were tested for the anti-herpesvirus activities and anti-proliferative activity. E-5-(2-Bromovinyl)uracil derivative (BV-DMDU) and its cytosine congener were synthesized from 1-β-D-arabinofuranosyl- E-5-(2-bromovinyl)uracil (BV-araU). 5-Bromo, 5-iodo, 5-methyl, and 5-ethyl derivatives of DMDU and BV-DMDU showed activities against herpes simplex virus type 1 (HSV-1) and varicella-zoster virus (VZV). The corresponding DMDC derivatives had no or only weak antiviral activity. Among the 2′-deoxy-2′-methylidene pyrimidine nucleosides, BV-DMDU showed the most potent and selective anti-VZV activity. BV-DMDU was more potent than acyclovir, but less active than BV-araU. BV-DMDU was inactive against human diploid and tumour cells. DMDC and F-DMDC (5-fluoro derivative) were potent inhibitors of HSV-1, herpes simplex virus type 2, VZV, and human cytomegalovirus (HCMV) and also had significant anti-proliferative activity. Their potency against HCMV was better than that of ganciclovir and araC. Some DMDU derivatives also showed anti-HCMV activity, but they had anti-proliferative activity. The anti-HCMV activity of these DMDC and DMDU compounds was generally more potent than those against HSV-1 and VZV thereof, suggesting the participation of cellular kinase in their antiviral action.

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Abstract A normal coordinate approach was used to generate ciystallographic packing candidates of a multitorsional polyimide synthesized from 3,3′,4,4′-benzophenonetetracarboxylic acid (BTDA) and 2,2-dimethyl-l,3-(4-aminophenoxy)propane (DMDA) (PI-2). Candidates were obtained under conditions of fixed axial advance of 24.6 Å per monomer, and imposed 2/1 helical or 1/0 transiational symmetry, consistent with the observed WAXD meridional layer line spacing [1]. The ability of comb in atori ally generated torsional states to adopt the desired geometry was examined. Necessary corrections to die conformational parameter equations originally derived by Kusanagi, et al. [2|, have been made. The procedure described allowed crystallographic conformations satisfying explicit geometric and MM3 intramolecular energy criteria to be generated for a linear multitorsional polyimide prior to the application of crystallographic screening or refinement procedures.

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Introduction: Dysregulated C-MYC signaling is associated with the pathogenesis and poor survival in aggressive lymphomas such as diffuse large B cell lymphoma (DLBCL). Despite intense investigation, direct inhibitors of C-MYC have not yet advanced to the clinic. Various structural elements, such as TOP (terminal oligopyrimidine tract) motif, guanine quartet (CGG) 4 motif, and polypurine sequences (AGAGAG), have been shown to impart high level of dependence on eukaryotic initiation factor 4F (eIF4F). The eIF4F is comprised of 3 subunits, including the mRNA 5ʹ-cap-binding subunit eIF4E, the large scaffolding subunit eIF4G, and the RNA helicase subunit eIF4A. In the current project, we have investigated targeting eIF4A as a novel therapeutic strategy in lymphoma. Pateamine A (PatA) is a natural product originally isolated from a New Zealand marine sponge, Mycale sp. DMDA-PatA, a first generation PatA analogue, has demonstrated in vivo activity in xenograft cancer models. DMDA-PatA acts by decreasing the interaction between eIF4A and eIF4G that specifically inhibits cap dependent translation. MZ-735 is a recently developed PatA analogue that is more potent than DMDA-PatA and less protein bound. Materials and Methods: MZ-735 was synthesized at the CPRIT Synthesis and Drug-Lead Discovery Laboratory at Baylor University. Cytotoxicity was evaluated in diffuse large B cell and Mantle cell lymphoma cell lines using CellTiter-Glo (Promega®). Western blot analysis was performed for the expressions of oncogenes. Global translation was determined using surface sensing of translation (SUnSET) assay and Polysome profile followed by Western blotting and qPCR. RNA sequencing (RNA-seq) was carried out on drug versus dimethyl sulfoxide (DMSO)-treated cells in DLBCL and MCL. An unbiased proteomics analysis was performed using TMT mass spectrometry. Omics data were analyzed by gene set enrichment analysis (GSEA) and Virtual Inference of Protein-activity by Enriched Regulon (VIPER) analysis. Results: MZ-735 were studied in 13 lymphoma cell lines. MZ-735 exhibited concentration- and time-dependent cytotoxicity in lymphoma cell lines at low nanomolar concentrations and showed minimal toxicity in normal PBMC cells. MZ-735 potently inhibits polysome formation, global protein synthesis and inhibits oncogene such as C-Myc and Cyclin D1 in DLBCL and MCL cells. An unbiased quantitative proteomics analysis was carried out to identify the immediate consequence of MZ-735 during a short exposure time of 3 hours. More than 5000 proteins were detected, of which 132 proteins were upregualated and 119 proteins were down regulated by more than twofold after MZ-735 treatment (P < 0.05; fold change, >2). Enrichment analysis suggested that Cancer hallmark proteins such as E2F target proteins, G2/M check point proteins and mitotic spindle proteins were highly enriched among these depleted proteins and the most affected downregulated pathways are cell cycle, cell division and chromosome segregation pathway. We are currently conducting RNAseq to determine whether the mRNA level change in the same or opposite direction as the protein level for any given gene across the genome. Furthermore, we will conduct proteomics and RNAseq in samples treated for longer time points, as the short exposure (3h) favors discovery of depleted proteins with very short half-lives. Conclusion: These results demonstrate that the PatA analogue MZ-735 can potently inhibit the translational apparatus in lymphoma. MZ-735 inhibits metabolic pathways required for cancer progression, leading to growth arrest and apoptosis in the lymphoma cells. MZ-735 and other eIF4A inhibitors represent a promising new class of anti-neoplastic agents, which may be particularly useful for silencing undruggable oncogenes such as C-MYC. Deep insights into the translational responses to eIF4A inhibitors at the single gene level will inform future development of this class of anti-neoplastic agents. Disclosures O'Connor: Allos Therapeutics: Consultancy; Acetylon Pharma: Other: Travel expenses, Research Funding; Celgene: Research Funding; Millenium: Consultancy, Honoraria, Other: Travel expenses, Research Funding; Mundipharma: Consultancy, Honoraria, Other: Travel expenses, Research Funding; Novartis: Consultancy, Honoraria; Roche: Research Funding; Seattle Genetics, Inc.: Consultancy, Other: Travel expenses, Research Funding; Spectrum Pharma: Consultancy, Other: Travel expenses, Research Funding.

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This work investigates the possibility of using fly ash (FA) and Vietnam residual rice husk ash (RHA) in producing unfired building bricks with applying densified mixture design algorithm (DMDA) method. In this research, little amount of cement was added into the mixtures as binder substitution. Unground rice husk ash (URHA), an agricultural by-product, was used as partial fine aggregate replacement (10% and 30%) in the mixtures. The solid bricks of 220×105×60 mm in size were prepared in this study. The hardened properties of the bricks were investigated including compressive strength, flexural strength and water absorption according to corresponding Vietnamese standards. Forming pressure of 35 MPa was applied to form the solid bricks in the mold. The test results show that all brick specimens obtained good mechanical properties, which were well conformed to Vietnamese standard. Compressive strength and flexural strength of the bricks were respectively in range of 13.81–22.06 MPa and 2.25–3.47 MPa. It was definitely proved many potential applications of FA and RHA in the production of unfired building bricks.

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This paper presents the results of the experimental works to investigate the use of waste limestone from water treatment industry as fine aggregate in green concrete. Two concrete mixtures with a constant water-to-binder ratio of 0.3 were prepared for this investigation, in which, the normal concrete mixture was designed following the guidelines of ACI 211 standard, while the green concrete mixture was designed using densified mixture design algorithm (DMDA) technology. For comparison, both types of concrete samples were subjected to the same test program, including fresh properties, compressive strength, strength efficiency of cement, drying shrinkage, electrical surface resistivity, ultrasonic pulse velocity, and thermal conductivity. Test results indicate that both concrete mixtures showed the excellent workability due to the round-shape of waste limestone aggregate and the use of superplasticizer. In addition, the green concrete mixture exhibited a better performance in terms of engineering properties and durability in comparison with the normal concrete mixture. The results of the present study further support the recycling and reuse of waste limestone as fine aggregate in the production of green concrete.

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This paper reports on the potential use of fly ash (FA) and residual rice husk ash (RHA) in producing unfired building bricks (UBB) with the application of densified mixture design algorithm (DMDA) method. In this study, little amount of cement (10–15%) was added into the mixtures as binder substitution. Whereas, unground rice husk ash (URHA), an agricultural by-product, was used as partial aggregate replacement (10–20%) in the mixtures. The UBB of 220×105×60 mm in size were prepared and the hardened properties of the bricks were tested including compressive strength, flexural strength, water absorption and bulk density according to Vietnamese standard. Forming pressure of 35 MPa was applied to form the solid bricks in the mold. The test results show that all brick specimens achieved very good mechanical properties. The compressive strength, flexural strength and water absorption of brick specimens were respectively in range of 16.1–22.1 MPa, 2.8–3.5 MPa and 9.5–14.8% and the other properties of the bricks were well conformed to related Vietnamese standard. It was definitely proved many potential applications of FA and RHA in the production of UBB.

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The General Curvilinear Coastal Ocean Model (GCCOM) is a 3D curvilinear, structured-mesh, non-hydrostatic, large-eddy simulation model that is capable of running oceanic simulations. GCCOM is an inherently computationally expensive model: it uses an elliptic solver for the dynamic pressure; meter-scale simulations requiring memory footprints on the order of 10 12 cells and terabytes of output data. As a solution for parallel optimization, the Fortran-interfaced Portable–Extensible Toolkit for Scientific Computation (PETSc) library was chosen as a framework to help reduce the complexity of managing the 3D geometry, to improve parallel algorithm design, and to provide a parallelized linear system solver and preconditioner. GCCOM discretizations are based on an Arakawa-C staggered grid, and PETSc DMDA (Data Management for Distributed Arrays) objects were used to provide communication and domain ownership management of the resultant multi-dimensional arrays, while the fully curvilinear Laplacian system for pressure is solved by the PETSc linear solver routines. In this paper, the framework design and architecture are described in detail, and results are presented that demonstrate the multiscale capabilities of the model and the parallel framework to 240 cores over domains of order 10 7 total cells per variable, and the correctness and performance of the multiphysics aspects of the model for a baseline experiment stratified seamount.

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ABSTRACT For most imprinted genes, a difference in expression between the maternal and paternal alleles is associated with a corresponding difference in DNA methylation that is localized to a differentially methylated domain (DMD). Removal of a gene's DMD leads to a loss of imprinting. These observations suggest that DMDs have a determinative role in genomic imprinting. To examine this possibility, we introduced sequences from the DMDs of the imprinted Igf2r, H19, and Snrpn genes into a nonimprinted derivative of the normally imprinted RSVIgmyc transgene, created by excising its own DMD. Hybrid transgenes with sequences from the Igf2r DMD2 were consistently imprinted, with the maternal allele being more methylated than the paternal allele. Only the repeated sequences within DMD2 were required for imprinting these transgenes. Hybrid transgenes containing H19 and Snrpn DMD sequences and ones containing sequences from the long terminal repeat of a murine intracisternal A particle retrotransposon were not imprinted. The Igf2r hybrid transgenes are comprised entirely of mouse genomic DNA and behave as endogenous imprinted genes in inbred wild-type and mutant mouse strains. These types of hybrid transgenes can be used to elucidate the functions of DMD sequences in genomic imprinting.

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ABSTRACTDimethylsulfoniopropionate (DMSP) is an organic sulfur compound that is rapidly metabolized by marine bacteria either by cleavage to dimethylsulfide (DMS) or demethylation to 3-methiolpropionate. The abundance and diversity of genes encoding bacterial DMS production (dddP) and demethylation (dmdA) were measured in the North Pacific subtropical gyre (NPSG) between May 2008 and February 2009 at Station ALOHA (22°45′N, 158°00′W) at two depths: 25 m and the deep chlorophyll maximum (DCM; ∼100 m). The highest abundance ofdmdAgenes was in May 2008 at 25 m, with ∼16.5% of cells harboring a gene in one of the eight subclades surveyed, while the highest abundance ofdddPgenes was in July 2008 at 25 m, with ∼2% of cells harboring a gene. ThedmdAgene pool was consistently dominated by homologs from SAR11 subclades, which was supported by findings in metagenomic data sets derived from Station ALOHA. Expression of the SAR11dmdAgenes was low, with typical transcript:gene ratios between 1:350 and 1:1,400. The abundance of DMSP genes was statistically different between 25 m and the DCM and correlated with a number of environmental variables, including primary production, photosynthetically active radiation, particulate DMSP, and DMS concentrations. At 25 m,dddPabundance was positively correlated with pigments that are diagnostic of diatoms; at the DCM,dmdAabundance was positively correlated with temperature. Based on gene abundance, we hypothesize that SAR11 bacterioplankton dominate DMSP cycling in the oligotrophic NPSG, with lesser but consistent involvement of other members of the bacterioplankton community.

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SummaryMicroinjection of anti-α-tubulin (Dm1A) inhibited progesterone-induced meiotic maturation in large follicle-enclosed oocytes of the frog, Rana pipiens. DM1A (46nl; 10mg/ml) injection significantly increased the ED50 value for progesterone as determined by germinal vesicle dissolution (GVD) bioassay. By contrast, low doses of microinjected DM1A (46nl; 2.5mg/ml), anti-actin (clone KJ43A), anti-cytokeratin (C-11), anti-intermediate filament antibody (IFA), generic IgG (46 nl; 20 mg/ml) or sodium azide (46 nl; 1 mg/ml), an antibody preservative, were without inhibitory effect in this bioassay. Microinjected, affinity-purified DM1A (46n1; 7.5mg/ml) was also inhibitory, but preabsorption with pure tubulin prior to injection significantly reduced the inhibitory effect. DM1A injection had no effect on centrifugation-induced germinal vesicle migration (GVM). Previous work indicated that drugs (e.g. demecolcine and nocodazole), which destabilise microtubules, enhance both centrifugation-induced GVM and progesterone-induced GVD in Rana oocytes. Taking these results together, it is suggested that DM1A injection may have differential effects on microtubules in this cell. Thus, while the majority of microtubules were apparentl depolymerised by DM1A (46nl; 10mg/ml) injection, a small subpopulation appeared to be stabilised as bundles. Confocal immunofluorescence microscopy of follicle-enclosed oocytes after DM1A injection revealed a major loss of microtubules throughout the cell however, apparent sparse bundles of nucrotubules arranged in an approximately 600 μm shell were associated with the injectate region 24h post-injection. By contrast, control follicle-enclosed oocytes topically labelled with DM1A post-fixation had extensive microtubule arrays similar to those previously reported in Xenopus oocytes. Intracellular recording after DM1A injection and progesterone treatment yielded an intermediate membrane potential (Vm= −31.8mV) compared with control (immature) DMIA-injected cells (Vm= −44.7 mV) or potassium balanced salt solution (KBS)-injected cells matured with progesterone (Vm= −13.9mV). These results suggest that DM1A injection does not completely inhibit electrophysiological changes initiated by progesterone. Working hypotheses are proposed that suggest a role for microtubules in the action of progesterone which normally lifts the prophase I block in the Rana follicle-enclosed oocyte.

Abstract:

ABSTRACTDimethylsulfoniopropionate (DMSP) is mainly produced by marine phytoplankton but is released into the microbial food web and degraded by marine bacteria to dimethyl sulfide (DMS) and other products. To reveal the abundance and distribution of bacterial DMSP degradation genes and the corresponding bacterial communities in relation to DMS and DMSP concentrations in seawater, we collected surface seawater samples from DMS hot spot sites during a cruise across the Pacific Ocean. We analyzed the genes encoding DMSP lyase (dddP) and DMSP demethylase (dmdA), which are responsible for the transformation of DMSP to DMS and DMSP assimilation, respectively. The averaged abundance (±standard deviation) of these DMSP degradation genes relative to that of the 16S rRNA genes was 33% ± 12%. The abundances of these genes showed large spatial variations.dddPgenes showed more variation in abundances thandmdAgenes. Multidimensional analysis based on the abundances of DMSP degradation genes and environmental factors revealed that the distribution pattern of these genes was influenced by chlorophyllaconcentrations and temperatures.dddPgenes,dmdAsubclade C/2 genes, anddmdAsubclade D genes exhibited significant correlations with the marineRoseobacterclade, SAR11 subgroup Ib, and SAR11 subgroup Ia, respectively. SAR11 subgroups Ia and Ib, which possesseddmdAgenes, were suggested to be the main potential DMSP consumers. TheRoseobacterclade members possessingdddPgenes in oligotrophic subtropical regions were possible DMS producers. These results suggest that DMSP degradation genes are abundant and widely distributed in the surface seawater and that the marine bacteria possessing these genes influence the degradation of DMSP and regulate the emissions of DMS in subtropical gyres of the Pacific Ocean.

Abstract:

U–Pb geochronology was applied to a combination of magmatic and hydrothermal minerals to help constrain the timing of emplacement of three units in the Mount Douglas Granite (MDG) and reveal their association with a complex mineralized hydrothermal system containing endogranitic Sn–W–Mo–Zn–Bi–U-bearing greisen/sheeted veins within the pluton. Magmatic monazite and zircon U–Pb ages obtained by LA–ICP–MS overlap at 368 Ma, recording a Late Devonian crystallization age for the MDG. Although discrimination, outside analytical error, of sequential pulses of magmatism is beyond the resolution of LA–ICP–MS U–Pb geochronology, geochemical variations of monazite accompanied by previous whole-rock geochemical analyses support a progressive fractional crystallization process starting from a parental magma (Dmd1), leading to the generation of Dmd2, and finally Dmd3 as the most fractionated unit. Hydrothermal uraninite, cassiterite, and monazite, collected from endogranitic greisen/sheeted veins, reveal evidence for syn-magmatic-related mineralization and a longer-lived post-magmatic hydrothermal system. The first stage is recorded by concordant uraninite dates at 367 ± 3 Ma and by an inverse isochron lower intercept of 362 ± 8 Ma for cassiterite. In contrast, hydrothermal monazite crystallized over a wider range of ages from 368 to 344 Ma, demonstrating post-magmatic hydrothermal activity within the MDG. These magmatic and hydrothermal ages combined with the geochemical signature of the MDG are similar to those documented for the nearby Mount Pleasant Sn–W–Mo–Bi–In granite-related deposit, which suggests that the two mineralizing systems occur at different levels of the same magmatic system.

Abstract:

Most of the phase change materials (PCMs) have been limited to use as functional additions or sealed in containers, and extra auxiliary equipment or supporting matrix is needed. The emergence of 3D printing technique has dramatically advanced the developments of materials and simplified production processes. This study focuses on a novel strategy to model thermal energy storage crystalline gels with three-dimensional architecture directly from liquid resin without supporting materials through light-induced polymerization 3D printing technique. A mask-projection stereolithography printer was used to measure the 3D printing test, and the printable characters of crystalline thermal energy storage P(SA-DMAA) gels with different molar ratios were evaluated. For the P(SA-DMMA) gels with a small fraction of SA, the 3D fabrication was realized with higher printing precision both on milli- and micro- meter scales. As a comparison of 3D printed samples, P(SA-DMAA) gels made by other two methods, post-UV curing treatment after 3D printing and UV curing using conventional mold, were prepared. The 3D printed P(SA-DMAA) gels shown high crystallinity. Post-UV curing treatment was beneficial to full curing of 3D printed gels, but did not lead to the further improvement of the crystal structure to get higher crystallinity. The P(SA-DMAA) crystalline gel having the highest energy storage enthalpy was developed, which reached 69.6 J·g−1. Its good thermoregulation property in the temperature range from 25 to 40 °C was proved. The P(SA-DMAA) gels are feasible for practical applications as one kind of 3D printing material with thermal energy storage and thermoregulation functionality.

Abstract:

Background: The objective of this study was to compare angular measurements in the evaluation of hallux valgus deformities using a goniometer and a computerized program to assess degree of concordance between the two methods and determine the reliability of manual measurements. Methods: Angles measured included the hallux valgus angle (HVA), the intermetatarsal angle (IMA), the distal metatarsal articular angle (DMAA), and the proximal phalangeal articular angle (PPAA), also called the hallux valgus interphalangeus angle or interphalangeal angle. Measurements were made on preoperative weightbearing radiographs in 176 patients with symptomatic hallux valgus. Manual measurements were made with a goniometer by an orthopaedic surgeon. An independent experienced technician used digitized images to perform angular measurements with the Autocad® software program (Autodesk Inc., San Rafael, CA). Results: HVA values obtained with the two techniques were similar. However, significantly higher mean values were obtained with the Autocad® for the IMA and PPAA measurements, and higher mean values were obtained for the DMAA measurement with the manual technique. Whereas differences were more or less randomly distributed for the HVA, in the remaining patients, measurements were clearly related to the measurement technique, i.e., for the DMAA, the manual technique had a tendency to show higher values, and for the IMA and PPAA the manual technique showed lower values than the computer. Correlations between both techniques for the different angular measurements were as follows: HVA, −0.179 ( p = 0.018); DMMA, −0.294 ( p >0.001); PPAA, −0.876 ( p >0.001); and IMA, −0.661 ( p >0.001). The intraclass correlation coefficient (ICC) showed that the concordance between manual and Autocad® angular measurements was excellent for the HVA ( ICC = 0.89) and DMAA ( ICC = 0.80) and very poor for the PPAA ( ICC = 0.11) and IMA ( ICC = 0.42). Conclusions: Angular measurements made on weightbearing radiographs with the Autocad® in patients with hallux valgus deformities were more reliable than those made with a goniometer. Although for large angles, such as HVA and DMAA, results obtained with both measurement techniques were similar. Manual measurements, however, may underestimate the true values of the smaller IMA and PPAA angles.

Abstract:

Hallux valgus is characterized by the appearance and growth of a painful “lump” in the region of the first metatarsophalangeal joint, the development of forefoot corns, and inability to choose the right shoes, which leads to a significant decrease in the quality of life of these patients. Corrective osteotomies that preserve the metatarsophalangeal joint, for example Austin (Chevron) osteotomy, are usually used for hallux valgus deformity of the I, II degrees. Radiography with the study of the hallux valgus angle (HVA), the intermetatarsal angle (IMA), the distal metatarsal articular angle (DMAA) is a research method that shows the true correlation between bone structures. The correlation between the radiological and functional indicators of osteotomy allows us to determine possible recommendations for indications for surgical treatment of Hallux valgus. Correlation shows that the largest correction of hallux valgus in older patients occurs due to a small adjustment of the angle of DMMA and HVA. IMA had the best correction after Austin osteotomy among patients of a younger age, then the HVA, and the DMMA had minimum correction according to the AOFAS rating scale (Kitaoka). The revealed correlations allow us to determine the correct tactics for the treatment of hallux valgus by identifying the benefits of Austin osteotomy.

Abstract:

Previous study reported that Nigella sativa has in vitro and in vivo cancer activity.This study was conducted to observe the effect of chloroform extract of Nigella sativa seed (NCE) on 7,12-Dimethylbenz[a]anthracene (DMBA)-induced female rats’ splenocyte. The experiment consisted of five groups, corn oil solvent control group, DMBA group, DMBA+250 mg/kgBW NCE, DMBA+500 mg/kgBW NCE and DMBA+750 mg/kgBW NCE. Extract was dissolved in corn oil and oral administered daily for 2 weeks before and during the DMBA induction. Observation of cell proliferation was performed using haematoxylin and eosin (H&E) and AgNOR stainings. H&E staining showed decreased necrocis activity extract groups compared to DMBA group. From AgNOR staining results, mean AgNOR (mAgNOR) of extract groups was less in number compared to DMBA group. The mAgNOR in corn oil solvent control group, DMBA group, DMBA+250 mg/kgBW NCE, DMBA+500 mg/kgBW NCE and DMBA+750 mg/kgBW NCE were 1.22, 1.91, 1.29, 1.36 and 1.33, respectively. Our current results showed that NCE reduces the proliferation of DMBA-induced rat spleenocytes Thus, NCE has potency to be developed as a chemopreventive agent.Keywords: Nigella sativa, spleen, DMBA, anti-proliferative

Abstract:

Category: Bunion Introduction/Purpose: Distal metatarsal articular angle (DMAA) is important for the treatment of hallux valgus deformity, because high DMAA is a cause of recurrence and stiffness after surgery. However, the DMAA is not commonly measured on plain radiograph, because of its low reliability. The reliability would be increased, if we clearly understand anatomical structure of the DMAA in hallux valgus deformity. In the WBCT, we found that the DMAA was different between dorsal side and plantar side. The purposes of this study were to compare the degree of the DMAA between dorsal side and plantar side in hallux valgus deformity, to identify which side of the DMAA is more correlated with the hallux valgus deformity, and to define standards for the DMAA measurement on plain radiograph. Methods: We retrospectively evaluated patients who underwent surgery for hallux valgus deformity in our clinic from April, 2017 to July, 2017. All patients underwent WBCT and plain weight-bearing radiograph preoperatively. The WBCT was performed using a cone-beam CT scanner (Planmed, Verity). For measuring the DMAA on axial plane image of the WBCT, we set axial plain parallel to sagittal axis of the 1st metatarsal bone. We determined dorsal and plantar axial WBCT images that located immediately below dorsal cortex and immediately over plantar cortex in the 1st metatarsal bone respectively. (Fig.1-A) We measured the DMAA on these dorsal and plantar axial WBCT images. (Fig.1-B) On the plain weight-bearing foot anteroposterior radiograph, we measured hallux valgus angle (HVA) and the DMAA. For measuring the DMAA on the plain radiograph, we defined the distal articular surface from sagittal groove at medial side to sharp edge at lateral side. (Fig. 1-C) Results: Thirty feet from 30 patients were included in this study. The mean age of patients was 55.6 years (range: 21-77). The mean of HVA was 34.9° (range: 22-52). The mean of the DMAA on the dorsal and the plantar axial WBCT images were 12.5°(0.7- 24.1) and 39.0°(16.7 – 57.6), respectively. Paired t test resulted that the DMAA on the plantar axial image was significantly higher than the DMAA on the dorsal axial image (P=0.000). Correlation analysis resulted that only the DMAA on the plantar coronal image was significantly correlated with the HVA (Pearson correlation coefficient:0.380, P=0.038). The intraclass coefficient indicated that the DMAA on the plain radiograph which defined in this study was highly reliable with the DMAA on the plantar coronal WBCT image.(ICC = 0.811) Conclusion: The present study showed that the plantar side DMAA is 27° higher than the dorsal side DMAA. We believed that this difference made confusion to define the DMAA on plain radiograph and decreased reliability for the measurement of the DMAA on the plain radiograph. Because the plantar side DMAA is more correlated with the HVA than the dorsal side DMAA, it is important to measure the plantar side DMAA on the plain radiograph. The present study proved that our definition of the DMAA on plain radiograph was appropriate for measuring the plantar side DMAA.

Abstract:

In the present work, the effectiveness of switchable hydrophobicity solvents (SHSs) as extraction solvent (N,N-Dimethylcyclohexylamine (DMCA), N,N-Diethylethanamine (TEA), and N,N-Benzyldimethylamine (DMBA)) for a variety of emerging pollutants was evaluated. Different pharmaceutical products (nonsteroidal anti-inflammatory drugs (NSAIDs), hormones, and triclosan) were selected as target analytes, covering a range of hydrophobicity (LogP) of 3.1 to 5.2. The optimized procedure was used for the determination of the target pharmaceutical analytes in wastewater samples as model analytical problem. Absolute extraction recoveries were in the range of 51% to 103%. The presented method permits the determination of the target analytes at the low ng mL−1 level, ranging from 0.8 to 5.9 (except for Triclosan, 106 ng mL−1) with good precision (relative standard deviation lower than 6%) using high-pressure liquid chromatography (HPLC) combined with ultraviolet (DAD) and fluorescence (FLR) detection. The microextraction alternative resulted in a fast, simple, and green method for a wide variety of analytes in environmental water sample. The results suggest that this type of solvent turns out to be a great alternative for the determination of different analytes in relatively complex water samples.

Abstract:

To test the effect of insulin treatment on the pharmacokinetics of metformin in rats with diabetes mellitus induced by alloxan (DMIA rats). The following results were reported from other studies. Metformin was metabolized via hepatic CYP2C11, 2D1, and 3A1/2 in rats. In DMIA rats, the protein expression and mRNA levels of hepatic CYP2C11 and 3A1/2 decreased and increased, respectively. In rat model of diabetes mellitus induced by streptozotocin, the protein expression of hepatic CYP2D1 was not changed. The increase in hepatic CYP1A2, 2B1, and 2E1, and decrease in hepatic CYP2C11 in DMIA rats was returned to the controls by insulin treatment. METHODS. Metformin (100 mg/kg) was administered intravenously and orally to the control rats, DMIA rats, and DMIA rats with insulin treatment for 3 weeks (DMIA rats with insulin). RESULTS. After intravenous administration of metformin to the DMIA rats, the CLR and CLNR of the drug were significantly slower than the controls. After oral administration of metformin to the DMIA rats, the AUC of the drug was also significantly greater than the controls. After intravenous administration of metformin to the DMIA rats with insulin, the significantly slower CLNR of the drug in the DMIA rats was returned to the controls. The altered pharmacokinetic indices observed following intravenous and oral administration of metformin to DMIA rats returned to the control values in the DMIA rats with insulin. CONCLUSIONS. The significantly slower CLNR of metformin in the DMIA rats could be due to the decrease in hepatic CYP2C11 than the controls. The comparable CLNR of metformin between the DMIA rats with insulin and the control rats could be due to restoration of hepatic CYP enzyme changes in DMIA rats to the controls.

Abstract:

Investigou-se o comportamento eletroquímico dos dímeros ciclopaladados [Pd(dmba)(mi-X)]2 [X = Cl (1), NCO (2), NCS (3), CN (4)] (dmba = N,N-dimetilbenzilamina) e do monômero [Pd(dmba)(MeCN)2][NO3] (MeCN = acetonitrila). Os resultados experimentais mostraram redução de Pd(II) para Pd(I) para os compostos 1-3, enquanto que somente para 1 observou-se a redução de Pd(I) para Pd(0) em uma única etapa. O complexo 5 mostrou redução de Pd(II) para Pd(0). Observou-se que a estabilidade eletroquímica destes compostos diminuem na seguinte ordem: [Pd(dmba)(mi-CN)]2 (4) > [Pd(dmba)(mi-NCO)]2 (2) > [Pd(dmba)(mi-SCN)]2 (3) > [Pd(dmba)(MeCN)2][NO3] (5) > [Pd(dmba)(mi-Cl)]2 (1).

Abstract:

Objective: Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM-5) disruptive mood dysregulation disorder (DMDD) is a controversial new diagnosis. No studies have investigated DMDD symptoms (irritable-angry mood and temper outbursts) and demographics in general population and psychiatric samples. Method: Maternal ratings of DMDD symptoms and diagnoses, age, gender, IQ, race, and parent occupation were analyzed in general population ( n = 665, 6-12 years) and psychiatric samples ( n = 2,256, 2-16 years). Results: Percentage of school-age children with DMDD symptoms were 9% general population, 12% ADHD-I, 39% ADHD-C, and 43% autism. Male, nonprofessional parent, and autism with IQ > 80 were associated with increasing DMDD symptoms, but demographics together explained only 2% to 3% of the DMDD score variance. Conclusion: Demographics contributed little to the presence of DMDD symptoms in all groups, whereas oppositional defiant disorder (ODD) explained most of the variance. Almost all children with DMDD symptoms had ODD suggesting that DMDD may not be distinct from ODD.

Abstract:

Abstract. Objective: According to DSM-5, Disruptive Mood Dysregulation Disorder (DMDD) is characterized by chronic temper outbursts and irritable moods. So far, little is known about its prevalence rate, course and influence on individual well-being. We assessed the prevalence rates of DMDD symptoms during adulthood and primary school age – the latter retrospectively – and studied their relationship with psychiatric disorders and socioeconomic variables. Methods: A total of 2,413 subjects, aged 18–94 years, participated in this population-based, representative study based on self-reports. Results: 12 (0.50 %) subjects reported elevated DMDD symptoms during adulthood, and 19 (0.79 %) reported elevated DMDD symptoms during primary school age. DMDD symptoms were associated with higher rates of depression and anxiety symptoms. Those reporting elevated DMDD symptoms during adulthood were more often single or divorced, and those reporting elevated DMDD symptoms during primary school age were more often childless and unemployed during adulthood compared to subjects without DMDD symptoms. Conclusions: DMDD symptoms seem to show a chronic course and go hand in hand with elevated psychiatric symptoms and impaired socioeconomic and demographic status.

Abstract:

1,3-Dimethylamylamine (1,3-DMAA) is a stimulant commercially sold in a variety of dietary supplements as a chemical species derived from geranium plants (Pelargonium graveolens). Whether 1,3-DMAA naturally occurs in geranium plants or other dietary ingredients, it has important regulatory and commercial ramifications. However, the analysis of 1,3-DMAA in geranium plants is not trivial due to low concentrations and a complex environmental matrix, requiring high selectivity and sensitivity. An extraction method combined with high performance liquid chromatography and tandem mass spectrometry is used to determine 1,3-DMAA and 1,4-dimethylamylamine (1,4-DMAA) concentrations in geranium plants with both external calibration and standard addition method. Samples from the Changzhou, Kunming, and Guiyang regions of China during both winter and summer were analyzed for 1,3-DMAA and 1,4-DMAA. The diastereomer ratios of the 1,3-DMAA stereoisomers of a racemic standard and the extracted plant were also quantified.

Abstract:

The role of dietary factors in inhibiting or delaying the development of non-melanoma skin cancer (NMSC) has been investigated for many years. Cardamom, which is a dietary phytoproduct, has been commonly used in cuisines for flavour and has numerous health benefits, such as improving digestion and stimulating metabolism and having antitumorigenic effects. We have investigated the efficacy of dietary cardamom against 7,12-dimethylbenz[a]anthracene (DMBA)-induced skin papillomatogenesis in Swiss albino mice that closely resembles human NMSC. Mice were grouped into normal wild type (untreated), vehicle-treated (acetone), carcinogen-treated (DMBA), and DMBA and cardamom-treated (DMBA+CARD) to delineate the role of cardamom against DMBA-induced papillomatogenesis. Oral administration of cardamom to DMBA-treated mice up-regulated the phase II detoxification enzymes, such as glutathione-S-transferase and glutathione peroxidase, probably via activation of nuclear factor erythroid-2-related factor 2 transcription factor in ‘DMBA+CARD’ mice. Furthermore, reduced glutathione, glutathione reductase, superoxide dismutase and catalase were also up-regulated by cardamom in the same ‘DMBA+CARD’ group of mice compared with DMBA-treated mice. Cardamom ingestion in DMBA-treated mice blocked NF-κB activation and down-regulated cyclo-oxygenase-2 expression. As a consequence, both the size and the number of skin papillomas generated on the skin due to the DMBA treatment were reduced in the ‘DMBA+CARD’ group. Thus, the results from the present study suggest that cardamom has a potential to become a pivotal chemopreventive agent to prevent papillomagenesis on the skin.

Abstract:

A proposta deste trabalho resultou da necessidade de se avaliar o potencial carcinogênico da uretana, em concentragoes mais baixas, a partir do modelo experimental de carcinogenese bucal DMBA-induzida. Cem hamsters sírios dourados foram separados em cinco grupos experimentais. 0 grupo 1 recebeu aplicações topicas de uretana 0.5% na borda lateral da língua; grupo 2, uretana 6%; grupo 3 uretana 0.5% + DMBA; grupo 4, uretana 6% + DMBA, e o grupo 5 — DMBA (controle positivo). Os dados obtidos mostraram que a uretana a 0.5% e 6% não induziu alterações histolOgicas nos grupos 1 e 2. A formação de carcinomas nos animais tratados com uretana e DMBA ocorreu em proporções menores quando comparada com o grupo controle positivo (DMBA). A uretana a 0.5% e 6% reduziu a carcinogenicidade do DMBA, e não apresentou potencial carcinogenic° de iniciação, promoção e/ou progressão.

Abstract:

Polyaromatic hydrocarbons (PAHs) are prevalent, potent carcinogens, and 7,12-dimethylbenz[a]anthracene (DMBA) is a model PAH widely used to study tumorigenesis. Mice lacking Langerhans cells (LCs), a signatory epidermal dendritic cell (DC), are protected from cutaneous chemical carcinogenesis, independent of T cell immunity. Investigation of the underlying mechanism revealed that LC-deficient skin was relatively resistant to DMBA-induced DNA damage. LCs efficiently metabolized DMBA to DMBA-trans-3,4-diol, an intermediate proximal to oncogenic Hras mutation, and DMBA-treated LC-deficient skin contained significantly fewer Hras mutations. Moreover, DMBA-trans-3,4-diol application bypassed tumor resistance in LC-deficient mice. Additionally, the genotoxic impact of DMBA on human keratinocytes was significantly increased by prior incubation with human-derived LC. Thus, tissue-associated DC can enhance chemical carcinogenesis via PAH metabolism, highlighting the complex relation between immune cells and carcinogenesis.

Abstract:

Kanker payudara dapat terjadi karena paparan dari senyawa 7,12-dimethylbenz (a) antrasene (DMBA) yang bersifat mutagenik dan karsinogenik. Drug of choice untuk kanker payudara adalah Doxorubicin, namun menimbulkan efek samping dan toksik pada sel normal maka diperlukan penelitian ko-kemoterapi dalam hal ini digunakan fraksi etil asetat akar pasak bumi yang dapat bersifat sebagai antiproliferasi. penelitian ini adalah untuk menelusuri mekanisme ko-kemoterapi akar pasak bumi dan Doxorubicin terhadap aktivitas proliferasi protein Ki-67 pada Tikus SD yang diinduksi DMBA. Akar pasak bumi (Eurycoma longifolia Jack) diekstraksi menggunakan pelarut etanol 70 % dan difraksinasi menggunakan etil asetat. Fraksi etil asetat akar pasak bumi diuji mekanisme molekulernya secara in vivo terhadap 5 Kelompok tikus galur Sprague Dawley terdiri atas Kelompok 1 hanya diberi pakan dan minum, Kelompok 2 diberikan DMBA dosis 20 mg/kgBB, Kelompok 3 diberikan DMBA 20 mg/kgBB + Doxorubicin 1,17 mg/kgBB, Kelompok 4 diberikan DMBA 20 mg/kgBB + fraksi etil asetat akar pasak bumi 100 mg/kgBB, Kelompok 5 diberikan DMBA 20 mg/kgBB + Doxorubicin 1,17 mg/kgBB + fraksi etil asetat akar pasak bumi 100 mg/kgBB kemudian dilakukan pembedahan dan uji imunohistokimia analisis data Kolmogorof Smirnof, uji Levene dan uji Kruskal Wallis. Hasil nilai rata-rata % ekspresi protein Ki-67 juga terjadi penurunan pada kelompok ko-kemoterapi DMBA + Doxorubicin + APB (8,89±3,20)% dibandingkan kelompok DMBA+Doxorubicin (12,73±3,37)% dan kelompok DMBA+APB (11,37±5,16)%, dan terdapat perbedaan yang bermakna dengan kelompok DMBA+Doxorubicin dengan nilai signifikansi 0,020 (p<0,05) namun tidak berdeda bermakna dengan DMBA+APB dengan nilai signifikansi 0,114 (p<0,05). Kesimpulan dari penelitian ini adalah pemberian ko-kemoterapi fraksi etil asetat akar pasak bumi dapat menurunkan ekpresi protein Ki-67 pada tikus model kanker payudara yang diinduksi DMBA