Fast enzymatic synthesis of n.c.a. 6-[18 F]fluorodopamine (FDA) from n.c.a. 6-[18 F]FDOPA and the fate of 6-FDOPA and 6-FDA in neuroblastoma and Caki-1 cells after their uptake.

The catecholamine analogue [123 I]mIBG has been used for scintigraphic imaging of neuroblastoma since 1984. It is taken up by the noradrenaline transporter (NAT), which is present in most neuroblastoma cells. An alternative imaging method could be PET with 6-[18 F]fluorodopamine, which is also taken up by NAT, but-in contrast to mIBG-also by dopamine transporter (DAT), present in neuroblastoma cells (NAT > DAT). An enzymatic method was established allowing a rapid, quantitative transformation of FDOPA to FDA by DOPA decarboxylase within 25 minutes. This strategy was applied to [18 F]FDOPA, which was produced via nucleophilic synthesis (RCY 15%, 10 GBq, 50 GBq/µmol) and subsequently converted to [18 F]FDA (RCY 35%-50%, n = 5). Uptake and metabolism of FDOPA and FDA were analyzed in human Kelly and SK-N-SH neuroblastoma cell lines and in human Caki-1 kidney cells that can take up catecholamines and mIBG via an organic cation transporter (OCT). FDOPA and FDA were taken up by all three cells, but FDOPA could only be converted to FDA in neuroblastoma cells. As today, [18 F]FDOPA is well available in high yields, efficient enzymatic conversion to [18 F]FDA to be used for NAT/DAT PET imaging in neuroendocrine tumors is an attractive, alternative synthesis route.

Supported Intermetallic PdZn Nanoparticles as Bifunctional Catalysts for the Direct Synthesis of Dimethyl Ether from CO-Rich Synthesis Gas.

The single-step syngas-to-dimethyl ether (STD) process entails economic and technical advantages over the current industrial two-step process. Pd/ZnO-based catalysts have recently emerged as interesting alternatives to currently used Cu/ZnO/Al2 O3 catalysts, but the nature of the active site(s), the reaction mechanism, and the role of Pd and ZnO in the solid catalyst are not well established. Now, Zn-stabilized Pd colloids with a size of 2 nm served as the key building blocks for the methanol active component in bifunctional Pd/ZnO-γ-Al2 O3 catalysts. The catalysts were characterized by combining high-pressure operando X-ray absorption spectroscopy and DFT calculations. The enhanced stability, longevity, and high dimethyl ether selectivity observed makes Pd/ZnO-γ-Al2 O3 an effective alternative system for the STD process compared to Cu/ZnO/γ-Al2 O3 .

Kinetics of the direct DME synthesis from CO2 rich syngas under variation of the CZA-to-γ-Al2O3 ratio of a mixed catalyst bed.

The one-step synthesis of dimethyl ether over mechanical mixtures of Cu/ZnO/Al2O3 (CZA) and γ-Al2O3 was studied in a wide range of process conditions. Experiments were performed at an industrially relevant pressure of 50 bar varying the carbon oxide ratio in the feed (CO2 in CO x from 20 to 80%), temperature (503-533 K), space-time (240-400 kgcat s mgas -3), and the CZA-to-γ-Al2O3 weight ratio (from 1 to 5). Factors favoring the DME production in the investigated range of conditions are an elevated temperature, a low CO2 content in the feed, and a CZA-to-γ-Al2O3 weight ratio of 2. A lumped kinetic model was parameterized to fit the experimental data, resulting in one of the predictive models with the broadest range of validity in the open literature for the CZA/γ-Al2O3 system.

Direct DME synthesis on CZZ/H-FER from variable CO2/CO syngas feeds.

Catalyst systems for the conversion of synthesis gas, which are tolerant to fluctuating CO/CO2 gas compositions, have great potential for process-technical applications, related to the expected changes in the supply of synthesis gas. Copper-based catalysts usually used in the synthesis of methanol play an important role in this context. We investigated the productivity characteristics for their application in direct dimethyl ether (DME) synthesis as a function of the CO2/CO x ratio over the complete range from 0 to 1. For this purpose, we compared an industrial Cu/ZnO/Al2O3 methanol catalyst with a self-developed Cu/ZnO/ZrO2 catalyst prepared by a continuous coprecipitation approach. For DME synthesis, catalysts were combined with two commercial dehydration catalysts, H-FER 20 and γ-Al2O3, respectively. Using a standard testing procedure, we determined the productivity characteristics in a temperature range between 483 K and 523 K in a fixed bed reactor. The combination of Cu/ZnO/ZrO2 and H-FER 20 provided the highest DME productivity with up to 1017 gDME (kgCu h)-1 at 523 K, 50 bar and 36 000 mlN (g h)-1 and achieved DME productivities higher than 689 gDME (kgCu h)-1 at all investigated CO2/CO x ratios under the mentioned conditions. With the use of Cu/ZnO/ZrO2//H-FER 20 a promising operating range between CO2/CO x 0.47 and 0.8 was found where CO as well as CO2 can be converted with high DME selectivity. First results on the long-term stability of the system Cu/ZnO/ZrO2//H-FER 20 showed an overall reduction of 27.0% over 545 h time on stream and 14.6% between 200 h and 545 h under variable feed conditions with a consistently high DME selectivity.

Formic Acid Formation by Clostridium ljungdahlii at Elevated Pressures of Carbon Dioxide and Hydrogen.

Low productivities of bioprocesses using gaseous carbon and energy sources are usually caused by the low solubility of those gases (e.g., H2 and CO). It has been suggested that increasing the partial pressure of those gases will result in higher dissolved concentrations and should, therefore, be helpful to overcome this obstacle. Investigations of the late 1980s with mixtures of hydrogen and carbon monoxide showed inhibitory effects of carbon monoxide partial pressures above 0.8 bar. Avoiding any effects of carbon monoxide, we investigate growth and product formation of Clostridium ljungdahlii at absolute process pressures of 1, 4, and 7 bar in batch stirred tank reactor cultivations with carbon dioxide and hydrogen as sole gaseous carbon and energy source. With increasing process pressure, the product spectrum shifts from mainly acetic acid and ethanol to almost only formic acid at a total system pressure of 7 bar. On the other hand, no significant changes in overall product yield can be observed. By keeping the amount of substance flow rate constant instead of the volumetric gas feed rate when increasing the process pressure, we increased the overall product yield of 7.5 times of what has been previously reported in the literature. After 90 h of cultivation at a total pressure of 7 bar a total of 4 g L-1 of products is produced consisting of 82.7 % formic acid, 15.6 % acetic acid, and 1.7 % ethanol.

Fast Pyrolysis of Biomass Residues in a Twin-screw Mixing Reactor.

Fast pyrolysis is being increasingly applied in commercial plants worldwide. They run exclusively on woody biomass, which has favorable properties for conversion with fast pyrolysis. In order to increase the synergies of food production and the energetic and/or material use of biomass, it is desirable to utilize residues from agricultural production, e.g., straw. The presented method is suitable for converting such a material on an industrial scale. The main features are presented and an example of mass balances from the conversion of several biomass residues is given. After conversion, fractionated condensation is applied in order to retrieve two condensates - an organic-rich and an aqueous-rich one. This design prevents the production of fast pyrolysis bio-oil that exhibits phase separation. A two phase bio-oil is to be expected because of the typically high ash content of straw biomass, which promotes the production of water of reaction during conversion. Both fractionated condensation and the use of biomass with high ash content demand a careful approach for establishing balances. Not all kind of balances are both meaningful and comparable to other results from the literature. Different balancing methods are presented, and the information that can be derived from them is discussed.

Splenic metastases--not a frequent problem, but an underestimate location of metastases: epidemiology and course.

OBJECTIVE: In the literature the frequency of splenic metastasis is documented very inconsistently. Only metastases of ovarial cancer are recommended for a surgical therapy. We examined the frequency of splenic metastasis in our hospital. METHOD: The data of the Tumorboard Schwerin has been analyzed for splenic metastases. Based on hospital documents and contact via telephone the clinical course of the patients was also examined. RESULTS: A total of 6,137 of 29,364 patients with malignant tumors developed metastases (20.9%). We found 59 of these patients with splenic metastases (0.96%; 0.002% of all patients with malignant tumors). Men were more frequently concerned then women. The median age of the patients was 62 (26-88) years. There are only a few primary tumors metastasized in more than 1% into the spleen. A total of 47% of these metastases were synchronous, 53% metachronous. Only three patients had isolated splenic metastasis. Two further patients also had lymph node metastasis in the splenic hilus. Two other patients developed liver metastases after splenectomy. We performed four splenectomies because of splenic metastasis. The survival of splenic metastasis was median 3 (0-61) months. DISCUSSION: The published studies of the frequency of the splenic metastasis are autopsy studies, which are not usable for epidemiological statements because of selection bias. We show that splenic metastases arise in less than 1% of all metastases. A splenectomy in case of splenic metastases makes sense, if the metastases are isolated. It is also meaningful as a debulking procedure that would be followed by a chemotherapy, e.g. in case of an ovarial carcinoma. As a result the survival is increased for patients undergoing splenectomy (median survival 19.5 vs. 3 months).

Identification and confirmation of increased fibrinopeptide a serum protein levels in gastric cancer sera by magnet bead assisted MALDI-TOF mass spectrometry.

Gastric cancer is the second most common malignancy and prognosis remains dismal. The reasons for the poor prognosis are the lack of sensitive serum markers for early detection and screening of high-risk individuals as well as the limited treatment options in advanced cancer stages. Using MALDI-TOF mass spectrometry after prefractionation of sera with magnet hydrophobic C8 coated beads sera from 14 patients with gastric cancer and 14 healthy controls mass spectra were generated. A peptide fragment was found to be highly elevated in cancer sera and was identified as fibrinopeptide A. To confirm proteome analysis of gastric cancer sera, we then screened a larger series of patients with gastric cancer (n = 99), high-risk individuals (n = 13) and normal controls (n = 111) for fibrinopeptide A serum levels. Interestingly, the mean logarithmic concentrations of serum fibrinopeptide A levels were significantly higher in cancer patients (mean 3.636 +/- 0.3738; p < 0.0001) and high-risk individuals (mean 3.569 +/- 0.4722; p < 0.05) compared to normal controls (mean 3.303 +/- 0.4012). In contrast, we observed no association of fibrinopeptide A levels with tumor stage, tumor location, presence of regional or distant metastasis, and Lauren type of gastric cancer. In conclusion, MALDI-TOF mass spectrometry of prefractionated gastric cancer sera allows the identification of potential biomarkers that may lead to the development of serum based tests for screening of high-risk individuals.

Nitrogen-starvation-induced chlorosis in Synechococcus PCC 7942: adaptation to long-term survival.

When deprived of essential nutrients, the non-diazotrophic cyanobacterium Synechococcus sp. strain PCC 7942 undergoes a proteolytic degradation of the phycobiliproteins, its major light-harvesting pigments. This process is known as chlorosis. This paper presents evidence that the degradation of phycobiliproteins is part of an acclimation process in which growing cells differentiate into non-pigmented cells able to endure long periods of starvation. The time course of degradation processes differs for various photosynthetic pigments, for photosystem I and photosystem II activities and is strongly influenced by the illumination and by the experimental conditions of nutrient deprivation. Under standard experimental conditions of combined nitrogen deprivation, three phases of the differentiation process can be defined. The first phase corresponds to the well-known phycobiliprotein degradation, in phase 2 the cells lose chlorophyll a prior to entering phase 3, the fully differentiated state, in which the cells are still able to regenerate pigmentation after the addition of nitrate to the culture. An analysis of the protein synthesis patterns by two-dimensional gel electrophoresis during nitrogen starvation indicates extensive differential gene expression, suggesting the operation of tight regulatory mechanisms.

Signal transduction protein P(II) is required for NtcA-regulated gene expression during nitrogen deprivation in the cyanobacterium Synechococcus elongatus strain PCC 7942.

The transcription factor of the cyclic AMP receptor protein/FNR family, NtcA, and the P(II) signaling protein play central roles in global nitrogen control in cyanobacteria. A dependence on P(II) for NtcA-regulated transcription, however, has not been observed. In the present investigation, we examined alterations in gene expression following nitrogen deprivation in Synechococcus elongatus strain PCC 7942 and specifically the roles of NtcA and P(II). Global changes in de novo protein synthesis following combined-nitrogen deprivation were visualized by in vivo [(35)S]methionine labeling and two-dimensional polyacrylamide gel electrophoresis analysis. Nearly all proteins whose synthesis responded specifically to combined-nitrogen deprivation in wild-type cells of S. elongatus failed to respond in P(II)- and NtcA-deficient mutants. One of the proteins whose synthesis was down-regulated in a P(II)- and NtcA-dependent manner was RbcS, the small subunit of RubisCO. Quantification of its mRNA revealed that the abundance of the rbcLS transcript following combined-nitrogen deprivation rapidly declined in wild-type cells but not in P(II) and NtcA mutant cells. To investigate further the relationship between P(II) and NtcA, fusions of the promotorless luxAB reporter genes to the NtcA-regulated glnB gene were constructed and these constructs were used to transform wild-type cells and P(II)(-) and NtcA(-) mutants. Determination of bioluminescence under different growth conditions showed that NtcA represses gene expression in the presence of ammonium in a P(II)-independent manner. By contrast, NtcA-dependent activation of glnB expression following combined-nitrogen deprivation was impaired in the absence of P(II). Together, these results suggest that under conditions of combined-nitrogen deprivation, the regulation of NtcA-dependent gene expression requires the P(II) signal transduction protein.