Untersuchungen zum DTG-Prozess an pelletierten Zeolithkatalysatoren

Hierarchische H-ZSM-5-Zeolithe sind eine aussichtsreiche Klasse heterogener Katalysatoren, welche bereits vielversprechende Ergebnisse in Literaturstudien gezeigt haben. Ein Beispiel ist die Herstellung von Benzinkomponenten aus biomassestämmigem Synthesegas über Dimethylether (DTG-Prozess). Durch die Herstellung von Benzin auf Basis nicht essbarer Biomasse kann dieser Ansatz zur Erreichung der Nachhaltigkeitsziele und zur Emissionsminderung im Transportsektor beitragen. Jedoch sind bei der Verwendung hierarchischer Zeolithe in Form technischer Katalysatorextrudate für diesen Prozess einige Aspekte nicht abschließend geklärt. Dazu zählen die Einflüsse der Bildung einer zusätzlichen mesoporösen Struktur und der Formgebung auf Eigenschaften und Wirksamkeit der Katalysatoren. In der vorliegenden Arbeit wurde eine Reihe von H-ZSM-5-Zeolithen mit hierarchischem Porensystem durch die Behandlung kommerziell verfügbarer Zeolithpulver mit alkalischen Lösungen hergestellt. Außerdem wurden die pulverförmigen Zeolithe mittels Extrusion zu technischen Katalysatoren geformt, wobei Silika- sowie Aluminabinder verwendet wurden. Die pulverförmigen und extrudierten Materialien wurden durch Anwendung folgender Methoden ausführlich charakterisiert: XRD, REM, TEM, WD-RFA, 29Si und 27Al MAS NMR, Pyridin-DRIFTS, NH3-TPD sowie hochauflösende Ar-Physisorption bei 87 K. Auf Basis dieser Untersuchungen wurde ein graphisch basiertes Modell für die Prozesse, die bei der alkalischen Behandlung beteiligt sind, entwickelt. Dieses Modell erweitert bereits publizierte Mechanismen aus der Literatur. Das Modell erklärt die Änderungen der Zeolithmorphologie, -porosität, -zusammensetzung und -azidität, welche durch die Behandlung hervorgerufen werden. Obwohl die Eigenschaften der pulverförmigen Zeolithe größtenteils in entsprechenden Extrudaten erhalten bleiben, werden die Einflüsse der jeweiligen keramischen Binder auf die katalytischen Charakteristika ebenfalls diskutiert. Insbesondere wurde festgestellt, dass sowohl der Silika- als auch der Aluminabinder den Gehalt an starken Säurezentren erhöhen, verursacht durch unterschiedliche Zeolith-Binder-Interaktion. Aktivität, Selektivität und Deaktivierungsneigung der extrudierten hierarchischen Zeolithkatalysatoren in der DTG-Reaktion wurde bei variabler und bei konstanter Verweilzeit bzw. Katalysatorbelastung untersucht. Beide Methoden führten im Wesentlichen zu übereinstimmenden Resultaten. Dies beweist die Eignung der Testung bei variabler Katalysatorbelastung als Methode zur Beurteilung der Katalysatorleistung mit verkürzter Versuchsdauer. Die Ergebnisse lassen darauf schließen, dass insbesondere eine moderate Azidität der Zeolithkomponente vorteilhaft hinsichtlich einer langsamen Katalysatordeaktivierung ist. Zwar haben weniger azide Katalysatoren geringere Aktivität, erreichen aber wesentlich höhere Umsatzkapazitäten. Darüber hinaus wird gezeigt, dass durch die bei der alkalischen Behandlung generierten Mesoporen ein effektiverer Abtransport der Koksvorläufer aus den Zeolithmikroporen erreicht wird. Gleiches gilt für die Verwendung eines mesoporösen Aluminabinders. Im Vergleich dazu führt ein Silikabinder mit breiter Meso- und Makroporosität zu einer schnelleren Deaktivierung. Hierbei spielt außerdem die unterschiedliche Aziditätsmodifikation der beiden Binder eine Rolle. Der Silikabinder bewirkt vermutlich die Heilung von Defekten im Zeolithgitter und den Abbau von Al-Spezies außerhalb des Gitters. Dies führt zu signifikant erhöhten Anteilen starker Säurezentren. Der Aluminabinder besitzt selbst eine mittelstarke Azidität. Auch er verursacht die Bildung zusätzlicher stark saurer Zentren, dies jedoch in geringerem Maße. Mögliche Ursache ist hier eine Migration von Al aus dem Binder in das Zeolithgitter. Die Analyse der gebrauchten Extrudate nach der Reaktion weist darauf hin, dass bei den untersuchten Reaktionsbedingungen die interne Verkokung den Hauptgrund für die Deaktivierung darstellt, obwohl sich der überwiegende Teil des Koks auf der externen Oberfläche bildet. Entsprechend erzielt ein mild alkalisch behandelter H-ZSM-5 mit relativ niedriger Azidität und Aluminabinder die höchste Lebenszeitausbeute an Benzinkomponenten. Eine stärkere alkalische Behandlung desselben Ausgangszeolithen führt zwar zur Bildung gesteigerter Mesoporosität, welche aber keine erhöhte Umsatzkapazität zur Folge hat. Stattdessen verschiebt sich die Selektivität in diesem Fall von Benzinkomponenten vor allem zu den kurzkettigen Olefinen Ethen und Propen. Mögliche Gründe sind eine gesteigerte Diffusivität dieser leichten Produkte und eine verminderte Wasserstofftransfer-Aktivität des stärker behandelten hierarchischen Zeolithen

Mesoporous H‐ZSM‐5 for the Conversion of Dimethyl Ether to Hydrocarbons

The potential of hierarchical H‐ZSM‐5 zeolites was studied for the conversion of DME to fuel‐compatible hydrocarbons. For this purpose, hierarchical H‐ZSM‐5 zeolites have been prepared from commercial H‐ZSM‐5 by desilication and organosilane‐directed hydrothermal synthesis. The zeolites were characterized by X‐ray diffraction, NH3‐TPD, DRIFTS, and N2 physisorption measurements. The catalysts have been tested in a tube reactor (1 bar, 648 K). The results indicate important structural changes in framework and acidic sites, which are significant for the synthesis of gasoline‐range hydrocarbons

Genome-wide association study identifies inversion in the CTRB1-CTRB2 locus to modify risk for alcoholic and non-alcoholic chronic pancreatitis

OBJECTIVE: Alcohol-related pancreatitis is associated with a disproportionately large number of hospitalisations among GI disorders. Despite its clinical importance, genetic susceptibility to alcoholic chronic pancreatitis (CP) is poorly characterised. To identify risk genes for alcoholic CP and to evaluate their relevance in non-alcoholic CP, we performed a genome-wide association study and functional characterisation of a new pancreatitis locus. DESIGN: 1959 European alcoholic CP patients and population-based controls from the KORA, LIFE and INCIPE studies (n=4708) as well as chronic alcoholics from the GESGA consortium (n=1332) were screened with Illumina technology. For replication, three European cohorts comprising 1650 patients with non-alcoholic CP and 6695 controls originating from the same countries were used. RESULTS: We replicated previously reported risk loci CLDN2-MORC4, CTRC, PRSS1-PRSS2 and SPINK1 in alcoholic CP patients. We identified CTRB1-CTRB2 (chymotrypsin B1 and B2) as a new risk locus with lead single-nucleotide polymorphism (SNP) rs8055167 (OR 1.35, 95% CI 1.23 to 1.6). We found that a 16.6 kb inversion in the CTRB1-CTRB2 locus was in linkage disequilibrium with the CP-associated SNPs and was best tagged by rs8048956. The association was replicated in three independent European non-alcoholic CP cohorts of 1650 patients and 6695 controls (OR 1.62, 95% CI 1.42 to 1.86). The inversion changes the expression ratio of the CTRB1 and CTRB2 isoforms and thereby affects protective trypsinogen degradation and ultimately pancreatitis risk. CONCLUSION: An inversion in the CTRB1-CTRB2 locus modifies risk for alcoholic and non-alcoholic CP indicating that common pathomechanisms are involved in these inflammatory disorders

A Concerted Action of Engrailed and Gooseberry-Neuro in Neuroblast 6-4 Is Triggering the Formation of Embryonic Posterior Commissure Bundles

One challenging question in neurogenesis concerns the identification of cues that trigger axonal growth and pathfinding to form stereotypic neuronal networks during the construction of a nervous system. Here, we show that in Drosophila, Engrailed (EN) and Gooseberry-Neuro (GsbN) act together as cofactors to build the posterior commissures (PCs), which shapes the ventral nerve cord. Indeed, we show that these two proteins are acting together in axon growth and midline crossing, and that this concerted action occurs at early development, in neuroblasts. More precisely, we identified that their expressions in NB 6-4 are necessary and sufficient to trigger the formation of the PCs, demonstrating that segmentation genes such as EN and GsbN play a crucial role in the determination of NB 6-4 in a way that will later influence growth and guidance of all the axons that form the PCs. We also demonstrate a more specific function of GsbN in differentiated neurons, leading to fasciculations between axons, which might be required to obtain PC mature axon bundles

dp53 Restrains Ectopic Neural Stem Cell Formation in the Drosophila Brain in a Non-Apoptotic Mechanism Involving Archipelago and Cyclin E

Accumulating evidence suggests that tumor-initiating stem cells or cancer stem cells (CSCs) possibly originating from normal stem cells may be the root cause of certain malignancies. How stem cell homeostasis is impaired in tumor tissues is not well understood, although certain tumor suppressors have been implicated. In this study, we use the Drosophila neural stem cells (NSCs) called neuroblasts as a model to study this process. Loss-of-function of Numb, a key cell fate determinant with well-conserved mammalian counterparts, leads to the formation of ectopic neuroblasts and a tumor phenotype in the larval brain. Overexpression of the Drosophila tumor suppressor p53 (dp53) was able to suppress ectopic neuroblast formation caused by numb loss-of-function. This occurred in a non-apoptotic manner and was independent of Dacapo, the fly counterpart of the well-characterized mammalian p53 target p21 involved in cellular senescence. The observation that dp53 affected Edu incorporation into neuroblasts led us to test the hypothesis that dp53 acts through regulation of factors involved in cell cycle progression. Our results show that the inhibitory effect of dp53 on ectopic neuroblast formation was mediated largely through its regulation of Cyclin E (Cyc E). Overexpression of Cyc E was able to abrogate dp53′s ability to rescue numb loss-of-function phenotypes. Increasing Cyc E levels by attenuating Archipelago (Ago), a recently identified transcriptional target of dp53 and a negative regulator of Cyc E, had similar effects. Conversely, reducing Cyc E activity by overexpressing Ago blocked ectopic neuroblast formation in numb mutant. Our results reveal an intimate connection between cell cycle progression and NSC self-renewal vs. differentiation control, and indicate that p53-mediated regulation of ectopic NSC self-renewal through the Ago/Cyc E axis becomes particularly important when NSC homeostasis is perturbed as in numb loss-of-function condition. This has important clinical implications

Wnt, Hedgehog and Junctional Armadillo/β-Catenin Establish Planar Polarity in the Drosophila Embryo

To generate specialized structures, cells must obtain positional and directional information. In multi-cellular organisms, cells use the non-canonical Wnt or planar cell polarity (PCP) signaling pathway to establish directionality within a cell. In vertebrates, several Wnt molecules have been proposed as permissible polarity signals, but none has been shown to provide a directional cue. While PCP signaling components are conserved from human to fly, no PCP ligands have been reported in Drosophila. Here we report that in the epidermis of the Drosophila embryo two signaling molecules, Hedgehog (Hh) and Wingless (Wg or Wnt1), provide directional cues that induce the proper orientation of Actin-rich structures in the larval cuticle. We further find that proper polarity in the late embryo also involves the asymmetric distribution and phosphorylation of Armadillo (Arm or β-catenin) at the membrane and that interference with this Arm phosphorylation leads to polarity defects. Our results suggest new roles for Hh and Wg as instructive polarizing cues that help establish directionality within a cell sheet, and a new polarity-signaling role for the membrane fraction of the oncoprotein Arm

Multi-Scale Modeling of HIV Infection in vitro and APOBEC3G-Based Anti-Retroviral Therapy

The human APOBEC3G is an innate restriction factor that, in the absence of Vif, restricts HIV-1 replication by inducing excessive deamination of cytidine residues in nascent reverse transcripts and inhibiting reverse transcription and integration. To shed light on impact of A3G-Vif interactions on HIV replication, we developed a multi-scale computational system consisting of intracellular (single-cell), cellular and extracellular (multicellular) events by using ordinary differential equations. The single-cell model describes molecular-level events within individual cells (such as production and degradation of host and viral proteins, and assembly and release of new virions), whereas the multicellular model describes the viral dynamics and multiple cycles of infection within a population of cells. We estimated the model parameters either directly from previously published experimental data or by running simulations to find the optimum values. We validated our integrated model by reproducing the results of in vitro T cell culture experiments. Crucially, both downstream effects of A3G (hypermutation and reduction of viral burst size) were necessary to replicate the experimental results in silico. We also used the model to study anti-HIV capability of several possible therapeutic strategies including: an antibody to Vif; upregulation of A3G; and mutated forms of A3G. According to our simulations, A3G with a mutated Vif binding site is predicted to be significantly more effective than other molecules at the same dose. Ultimately, we performed sensitivity analysis to identify important model parameters. The results showed that the timing of particle formation and virus release had the highest impacts on HIV replication. The model also predicted that the degradation of A3G by Vif is not a crucial step in HIV pathogenesis

Cancer Genomics Identifies Regulatory Gene Networks Associated with the Transition from Dysplasia to Advanced Lung Adenocarcinomas Induced by c-Raf-1

Background: Lung cancer is a leading cause of cancer morbidity. To improve an understanding of molecular causes of disease a transgenic mouse model was investigated where targeted expression of the serine threonine kinase c-Raf to respiratory epithelium induced initialy dysplasia and subsequently adenocarcinomas. This enables dissection of genetic events associated with precancerous and cancerous lesions. Methodology/Principal Findings: By laser microdissection cancer cell populations were harvested and subjected to whole genome expression analyses. Overall 473 and 541 genes were significantly regulated, when cancer versus transgenic and non-transgenic cells were compared, giving rise to three distinct and one common regulatory gene network. At advanced stages of tumor growth predominately repression of gene expression was observed, but genes previously shown to be upregulated in dysplasia were also up-regulated in solid tumors. Regulation of developmental programs as well as epithelial mesenchymal and mesenchymal endothelial transition was a hall mark of adenocarcinomas. Additionaly, genes coding for cell adhesion, i.e. the integrins and the tight and gap junction proteins were repressed, whereas ligands for receptor tyrosine kinase such as epi- and amphiregulin were up-regulated. Notably, Vegfr- 2 and its ligand Vegfd, as well as Notch and Wnt signalling cascades were regulated as were glycosylases that influence cellular recognition. Other regulated signalling molecules included guanine exchange factors that play a role in an activation of the MAP kinases while several tumor suppressors i.e. Mcc, Hey1, Fat3, Armcx1 and Reck were significantly repressed. Finally, probable molecular switches forcing dysplastic cells into malignantly transformed cells could be identified. Conclusions/Significance: This study provides insight into molecular pertubations allowing dysplasia to progress further to adenocarcinoma induced by exaggerted c-Raf kinase activity

G-protein signaling: back to the future

Heterotrimeric G-proteins are intracellular partners of G-protein-coupled receptors (GPCRs). GPCRs act on inactive Gα·GDP/Gβγ heterotrimers to promote GDP release and GTP binding, resulting in liberation of Gα from Gβγ. Gα·GTP and Gβγ target effectors including adenylyl cyclases, phospholipases and ion channels. Signaling is terminated by intrinsic GTPase activity of Gα and heterotrimer reformation — a cycle accelerated by ‘regulators of G-protein signaling’ (RGS proteins). Recent studies have identified several unconventional G-protein signaling pathways that diverge from this standard model. Whereas phospholipase C (PLC) β is activated by Gαq and Gβγ, novel PLC isoforms are regulated by both heterotrimeric and Ras-superfamily G-proteins. An Arabidopsis protein has been discovered containing both GPCR and RGS domains within the same protein. Most surprisingly, a receptor-independent Gα nucleotide cycle that regulates cell division has been delineated in both Caenorhabditis elegans and Drosophila melanogaster. Here, we revisit classical heterotrimeric G-protein signaling and explore these new, non-canonical G-protein signaling pathways

APOBEC3G-Augmented Stem Cell Therapy to Modulate HIV Replication: A Computational Study

PMC3661658The interplay between the innate immune system restriction factor APOBEC3G and the HIV protein Vif is a key host-retrovirus interaction. APOBEC3G can counteract HIV infection in at least two ways: by inducing lethal mutations on the viral cDNA; and by blocking steps in reverse transcription and viral integration into the host genome. HIV-Vif blocks these antiviral functions of APOBEC3G by impeding its encapsulation. Nonetheless, it has been shown that overexpression of APOBEC3G, or interfering with APOBEC3G-Vif binding, can efficiently block in vitro HIV replication. Some clinical studies have also suggested that high levels of APOBEC3G expression in HIV patients are correlated with increased CD4+ T cell count and low levels of viral load; however, other studies have reported contradictory results and challenged this observation. Stem cell therapy to replace a patient's immune cells with cells that are more HIV-resistant is a promising approach. Pre-implantation gene transfection of these stem cells can augment the HIV-resistance of progeny CD4+ T cells. As a protein, APOBEC3G has the advantage that it can be genetically encoded, while small molecules cannot. We have developed a mathematical model to quantitatively study the effects on in vivo HIV replication of therapeutic delivery of CD34+ stem cells transfected to overexpress APOBEC3G. Our model suggests that stem cell therapy resulting in a high fraction of APOBEC3G-overexpressing CD4+ T cells can effectively inhibit in vivo HIV replication. We extended our model to simulate the combination of APOBEC3G therapy with other biological activities, to estimate the likelihood of improved outcomes.JH Libraries Open Access Fun