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Three pilot-scale experiments have been conducted at SINTEF/NTNU in a 440 kVA AC electric furnace to demonstrate the process operation, energy requirements and CO2 emissions in the production of high carbon ferromanganese alloys. Comilog, UMK and Nchwaning (Assmang) ores blended with other materials, such as sinter and flux, thus achieving different charge mixtures have been utilized in the experiments. In the prereduction zone, higher manganese oxides in the ore are reduced to MnO through solid-gas exothermic reactions and at a temperature around 800oC, the unwanted endothermic Boudouard reaction is also active. As such, the total coke and energy consumption is highly dependent on if the prereduction occurs by CO gas or solid C. The pilot furnace has been excavated after each experiment and the extent of prereduction of the ore has been investigated by collecting samples from specific regions in the prereduction zone. In addition, material, and energy balance calculations for the three pilot experiments have been calculated using HSC Chemistry software. The HSC material and energy balance calculations have shown that the slag/alloy ratios, metal analyses, carbon consumption and the overall energy consumption are mainly affected by the composition of the charge mixtures. The relationship between the specific carbon consumption, the off-gas CO2/(CO2+CO) ratio and energy consumption to produce 1 tonne of HCFeMn alloy is discussed for the three different pilot-scale scenarios.

Pretreatment of manganese ores with sustainable energy sources has a potential for reducing energy consumption and CO2 emissions in manganese alloy production. Technologies to obtain this are currently being developed in EU H2020 project PreMa. Pretreatment of industrial manganese ores with different gas composition have been investigated experimentally in 1 kg scale with ore sizes used in industry. Degree of prereduction and fines formation varied with ore sources as well as with gas atmosphere and temperature. By heating in Argon, air, or CO2 gas the Mn-oxides were reduced to Mn2O3. Further reduction towards and down to MnO was only obtained when CO-containing gas was used. On-set temperatures for the different reactions are discussed

Recent excavations of Norwegian medium size SiMn furnaces have revealed spectacular amounts of carbide-rich materials accumulating on the sidewalls. In an excavated furnace from Eramet Kvinesdal, producing a 19%Si silicomanganese alloy prior shutdown, the sidewall materials contained silicon carbide in addition to SiMn alloy, slag and carbon. This contrasts with the large amounts of titanium carbides found in a furnace from Ferroglobe (Glencore then) which was producing 16%Si silicomanganese. The significant volume occupied by the carbides is likely to affect the flow of materials as well as furnace operation. It is therefore meaningful to understand how and when those carbides can form, especially concerning titanium carbide given the low content of titanium (about 0.3%) in the raw materials. The present study investigates the conditions under which TiC and SiC can appear in the furnace. Slag, alloy, and gas compositions were chosen to mimic industrial charges and were reacted between 1450 and 1650 °C. The reacted samples were further analysed by electron probe microanalysis with wavelength-dispersive X-ray spectroscopy (EPMA/WDS). Thermodynamic calculations were conducted using FactSage 8.0 and used for further reflection. The results indicate that TiC was formed by both precipitation and chemical reaction.

Dopamine D2 receptors (D2-R) in extrastriatal brain regions are of high interest for research in a wide range of psychiatric and neurologic disorders. Pharmacological competition studies and test-retest experiments have shown high validity and reliability of the positron emission tomography (PET) radioligand [11C]FLB 457 for D2-R quantification in extrastriatal brain regions. However, this radioligand is not available at most research centres. Instead, the medium affinity radioligand [11C]raclopride, which has been extensively validated for quantification of D2-R in the high-density region striatum, has been applied also in studies on extrastriatal D2-R. Recently, the validity of this approach has been questioned by observations of low occupancy of [11C]raclopride in extrastriatal regions in a pharmacological competition study with quetiapine. Here, we utilise a data set of 16 healthy control subjects examined with both [11C]raclopride and [11C]FLB 457 to assess the correlation in binding potential (BPND) in extrastriatal brain regions. BPND was quantified using the simplified reference tissue model with cerebellum as reference region. The rank order of mean regional BPND values were similar for both radioligands, and corresponded to previously reported data, both post-mortem and using PET. Nevertheless, weak to moderate within-subject correlations were observed between [11C]raclopride and [11C]FLB 457 BPND extrastriatally (Pearson's R: 0.30 - 0.56), in contrast to very strong correlations between repeated [11C]FLB 457 measurements (Pearson's R: 0.82 - 0.98). In comparison, correlations between repeated [11C]raclopride measurements were low to moderate (Pearson's R: 0.28 - 0.75). These results are likely related to low signal to noise ratio of [11C]raclopride in extrastriatal brain regions, and further strengthen the recommendation that extrastriatal D2-R measures obtained with [11C]raclopride should be interpreted with caution.

Background Survival in recurrent ependymomas in children and adolescents mainly depends on the extent of resection. Studies on repeated radiotherapy and chemotherapy at relapse have shown conflicting results. Methods Using data from the German multi-center E-HIT-REZ-2005 study, we examined the role of local therapy and the efficacy of chemotherapy with blockwise temozolomide (TMZ) in children and adolescents with recurrent ependymomas. Results Fifty-three patients with a median age of 6.9 years (1.25–25.4) at first recurrence and a median follow-up time of 36 months (2–115) were recruited. Gross- and near-total resection (GTR/NTR) were achieved in 34 (64.2%) patients and associated with a markedly improved 5-year overall survival (OS) of 48.7% vs. 5.3% in less than GTR/NTR. Radiotherapy showed no improvement in OS following complete resection (OS: 70 (CI: 19.9–120.1) vs. 95 (CI: 20.7–169.4) months), but an advantage was found in less than GTR/NTR (OS: 22 (CI: 12.7–31.3) vs. 7 (CI: 0–15.8) months). Following the application of TMZ, disease progression was observed in most evaluable cases (18/21). A subsequent change to oral etoposide and trofosfamide showed no improved response. PF-A EPN were most abundant in relapses (n = 27). RELA-positive EPN (n = 5) had a 5-year OS of 0%. Conclusion The extent of resection is the most important predictor of survival at relapse. Focal re-irradiation is a useful approach if complete resection cannot be achieved, but no additional benefit was seen after GTR/NTR. Longer-term disease stabilization (>6 months) mediated by TMZ occurred in a small number of cases (14.3%).

APETx2 is a peptide isolated from the sea anemone Anthopleura elegantissima. It is the most potent and selective inhibitor of acid-sensing ion channel 3 (ASIC3) and it is currently in preclinical studies as a novel analgesic for the treatment of chronic inflammatory pain. As a peptide it faces many challenges in the drug development process, including the potential lack of stability often associated with therapeutic peptides. In this study we determined the susceptibility of wild-type APETx2 to trypsin and pepsin and tested the applicability of backbone cyclisation as a strategy to improve its resistance to enzymatic degradation. Cyclisation with either a six-, seven- or eight-residue linker vastly improved the protease resistance of APETx2 but substantially decreased its potency against ASIC3. This suggests that either the N- or C-terminus of APETx2 is involved in its interaction with the channel, which we confirmed by making N- and C-terminal truncations. Truncation of either terminus, but especially the N-terminus, has detrimental effects on the ability of APETx2 to inhibit ASIC3. The current work indicates that cyclisation is unlikely to be a suitable strategy for stabilising APETx2, unless linkers can be engineered that do not interfere with binding to ASIC3.

Acid sensing ion channels (ASICs) are pH-sensitive channels that are distributed in the central and peripheral nervous system and which are believed to play a key role in pain perception. APETx2, a 42-residue peptide toxin isolated from the sea anemone Anthopleura elegantissima, is the only known selective inhibitor of ASIC3 channels. Here we describe the total chemical synthesis of APETx2 by solid-phase peptide synthesis and native chemical ligation. The folded synthetic toxin had an IC(50) of 57 nM for inhibition of rat ASIC3 channels expressed in Xenopus oocytes, in agreement with the IC(50) reported for the native toxin (63 nM). The native chemical ligation approach should provide an efficient route for synthesis of other pharmacologically useful disulfide-rich toxins from venomous animals.

The sea anemone peptide APETx2 is a potent and selective blocker of acid-sensing ion channel 3 (ASIC3). APETx2 is analgesic in a variety of rodent pain models, but the lack of knowledge of its pharmacophore and binding site on ASIC3 has impeded development of improved analogues. Here we present a detailed structure-activity relationship study of APETx2. Determination of a high-resolution structure of APETx2 combined with scanning mutagenesis revealed a cluster of aromatic and basic residues that mediate its interaction with ASIC3. We show that APETx2 also inhibits the off-target hERG channel by reducing the maximal current amplitude and shifting the voltage dependence of activation to more positive potentials. Electrophysiological screening of selected APETx2 mutants revealed partial overlap between the surfaces on APETx2 that mediate its interaction with ASIC3 and hERG. Characterization of the molecular basis of these interactions is an important first step toward the rational design of more selective APETx2 analogues.

When power electronic systems are connected to the medium-voltage grid, often multilevel topologies consisting of a number of cascaded converter cells are considered. For a given grid voltage level, either few cells featuring semiconductors with high blocking voltage capability or many cells using low-voltage semiconductors can be employed. This paper proposes efficiency/power density (η-ρ) Pareto analysis to comprehensively identify the optimum number of cascaded cells. Recent advances in silicon carbide (SiC) semiconductor technology point towards devices with blocking voltages exceeding 15kV. The switching characteristics that hypothetical SiC devices would have to provide in order to realize a simple single-stage full-bridge converter competitive to a multilevel solution are derived and found to be impracticably fast. Furthermore, it is shown that reliability concerns arising with increasing number of cascaded cells can be mitigated by means of redundancy.

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Nanoscale chemical patterning of different chemical species (amine, thiol, aldehyde, and biotin) in independent nanopatterns is achieved by the iterative application of thermochemical nanolithography (TCN L) to inscribe amine patterns followed by their chemical conversion to other functional groups. Due to the unique chemical stability of the patterns, the resultant substrates can be stored for weeks and subsequently be used for covalent and molecular-recognition-based attachment of nano-objects using standard chemical protocols. In particular, the ability of this method to attach proteins and DNA to the chemical nanopatterns and to create co-patterns of two distinctive bioactive proteins is demonstrated.

Vc1.1 is a disulfide-rich peptide inhibitor of nicotinic acetylcholine receptors that has stimulated considerable interest in these receptors as potential therapeutic targets for the treatment of neuropathic pain. Here we present an extensive series of mutational studies in which all residues except the conserved cysteines were mutated separately to Ala, Asp, or Lys. The effect on acetylcholine (ACh)-evoked membrane currents at the alpha9alpha10 nicotinic acetylcholine receptor (nAChR), which has been implicated as a target in the alleviation of neuropathic pain, was then observed. The analogs were characterized by NMR spectroscopy to determine the effects of mutations on structure. The structural fold was found to be preserved in all peptides except where Pro was substituted. Electrophysiological studies showed that the key residues for functional activity are Asp(5)-Arg(7) and Asp(11)-Ile(15), because changes at these positions resulted in the loss of activity at the alpha9alpha10 nAChR. Interestingly, the S4K and N9A analogs were more potent than Vc1.1 itself. A second generation of mutants was synthesized, namely N9G, N9I, N9L, S4R, and S4K+N9A, all of which were more potent than Vc1.1 at both the rat alpha9alpha10 and the human alpha9/rat alpha10 hybrid receptor, providing a mechanistic insight into the key residues involved in eliciting the biological function of Vc1.1. The most potent analogs were also tested at the alpha3beta2, alpha3beta4, and alpha7 nAChR subtypes to determine their selectivity. All mutants tested were most selective for the alpha9alpha10 nAChR. These findings provide valuable insight into the interaction of Vc1.1 with the alpha9alpha10 nAChR subtype and will help in the further development of analogs of Vc1.1 as analgesic drugs.

Scanning probe-based chemical nanolithography has been recognized as an essential part of future nanofabrication processes. However, most of the present strategies still have significant limitations in terms of throughput, resolution and substrate variety. Recently, we have developed a new chemical nanolithography technique called thermo-chemical nanolithography (TCNL). TCNL utilizes a resistively-heated atomic force microscope tip to thermally activate a chemical reaction on an arbitrary organic or inorganic substrate surface. TCNL can write well-defined chemical features at a rate of mm/s, with sub-15 nm resolution [1]. In particular, we have demonstrated that carboxylic ester groups on a polymer surface can be deprotected by TCNL to give carboxylic acids and further modified to form anhydrides [2]. Therefore, TCNL can tune surface wettability with in situ write-read-overwrite capability. In addition, nanoarrays of TCNL-activated amine groups have been used as anchor sites to immobilize a variety of biological ligands [3]. This proves TCNL to be a powerful tool to control the physical placement of biomolecules and cells. It can be applied to a range of molecular cell biology studies such as ligand-receptor recognition and cell signaling.1. R. Szoszkiewicz, T. Okada, S. C. Jones, T.-D. Li, W. P. King, S. R. Marder, and E. Riedo, Nano Lett. 7, 1064 (2007).2. D. B. Wang, R. Szoszkiewicz, T. Okada, S. C. Jones, M. Lucas, J. Lee, W. P. King, S. R. Marder, and E. Riedo, Appl. Phys. Lett. 91, 243104 (2007).3. D. Wang, V. Kodali, W. D. Underwood, J. E. Jarvholm, T. Odaka, S. J. Jones, C. Rumi, W. P. King, S. R. Marder, J.E. Curtis and E. Riedo, (2008) in preparation.

Use of graphitic (hexabenzocoronene-derived) molecules produces cholesteric ribbons which serve as molecular resists in a fluorine plasma. This procedure allows the shape of the molecular assemblies to be etched into the underlying silicon, validating the concept of “molecular resists”.

In this study dynamic 99 Tc m -HIDA single photon emission tomography (SPET) was performed in patients with primary sclerosing cholangitis and normal test subjects. The method offers the possibility of functional analysis of individual liver segments. After injection of 120 MBq of 99 Tc m -HIDA, 12 consecutive SPET examinations were performed at 6-min intervals. The segmental borders of liver segments as seen on computed tomography or magnetic resonance examinations were superimposed on the scintigraphic images allowing placement of regions of interest (ROIs) in specific liver segments. Sampling from the same ROIs in consecutive SPET images enabled creation of time-activity curves for individual liver segments. A range of normal values was created by quantitative analysis of normal volunteer studies. Results of the studies in patients correlated well with cholangiographic extent of disease, liver function tests and histological stage. The technique may have particular value in diseases that affect the liver in a non-homogenous or segmental fashion. Giving an indication of bile clearance from individual liver segments, it can quantify the functional importance of radiologically detected strictures. Percutaneous liver biopsy can be directed to the worst affected parts of the liver, making biopsy more representative. Sequential studies may allow monitoring of disease progression, aiding in selection and timing of therapeutic procedures.

Eight new C5-substituted derivatives of the potential atypical antipsychotic agent 5-methoxy-2-[N-(2-benzamidoethyl)-N-n-propylamino]tetralin (5-OMe-BPAT, 1) have been prepared by chemical conversion of the 5-trifluoromethylsulfonyloxy (triflate) analogue 4 via various Stille-type cross-couplings, a Heck reaction, and an amidation in moderate to good yields. The 5-acetyl, 5-cyano, 5-methyl, 5-(2-furyl), 5-phenyl, methyl 5-carboxylate, and the 5-carboxamido analogues 5-11 thus obtained, the previously disclosed 5-methoxy, 5-hydroxy, and 5-unsubstituted analogues 1-3, and the 5-triflate analogue 4 were evaluated for their ability to compete for [3H]-spiperone binding to rat striatal membranes containing dopamine D2 receptors, and their ability to compete for [3H]-8-OH-DPAT binding to rat frontal cortex membranes containing serotonin 5-HT1A receptors in vitro. Compounds 1-11 displayed weak to high affinities for dopamine D2 receptors, with Ki-values ranging from 550 nM for the 5-carboxamido analogue to 4.9 nM for the 5-hydroxy analogue. The relative affinities of the 5-methoxy, 5-hydroxy, and 5-unsubstituted analogues suggested that these compounds may bind to the same site and in a similar way as the 5-oxygenated DPATs, with the 5-methoxy substituent of 1 functioning as a hydrogen bond acceptor. The serotonin 5-HT1A receptor tolerated more structural diversity at the C5-position of 1, as revealed by the higher Ki-values of 1-11, which ranged from 60 nM for the 5-carboxamido analogue to 1.0 nM for the 5-unsubstituted analogue. Partial least-squares (PLS) analysis of a set of 24 molecular descriptors, generated for each analogue, revealed no significant correlation between the dopamine D2 receptor affinities of 1-11 and their molecular properties, supporting the view that they may have different binding modes at this receptor subtype. A PLS model with moderate predictability (Q2 = 0.49) could be derived for the serotonin 5-HT1A receptor affinities of 1-11. According to the model, a relatively lipophilic, nonpolar C5-substituent should be optimal for a high affinity at this receptor subtype.

1. 1. Conjugation of Tetrahymena enhanced the incorporation of glycine into the nuclear fraction by 500%. 2. 2. Incorporation of glycine into the microsomal supernatant was augmented by almost 500% by conjugation. 3. 3. Mitochondrial incorporation was stimulated nearly 3-fold in the conjugating strains while the incorporation of glycine into the microsomes was enhanced approximately 2.5 times. 4. 4. In the whole cell, glycine incorporation was increased nearly 2-fold by conjugation. 5. 5. Strong nuclear involvement was indicated by elevated metabolic activity and incorporation of glycine into RNA and DNA. 6. 6. Stimulation of the metabolism of Tetrahymena by cell communication suggests that the contents of a cell can have a synergistic effect on another cell. 7. 7. Augmentation of the biosynthetic capacities of cells by fusion is a demonstration of the dominant role of the cell membrane in the regulation and control of cells. 8. 8. Enhancement of biosynthesis of nuclear proteins in conjugating strains of cells indicates that fusion gives rise to the synthesis of new protein from previously existing protein or protein procursors. 9. 9. The specific activities of the subcellular fractions after the incorporation of glycine into 2 separated starved strains of Tetrahymena followed the usual pattern of nucleus less than whole cells, whole cells less than mitochondria, mitochondria less than microsomes, but with the microsomal supernatant being much greater than that of the microsomes.

1. 1. A membrane glycoprotein was isolated from Tetrahymena surface membrane with properties similar to mammalian erythrocyte glycoprotein. 2. 2. This membrane glycoprotein had a specific acitivity less than whole membrane at various time intervals up to 40 hr. 3. 3. In double labelling experiments, glucosamine contributed a greater degree of the labelling of this glycoprotein than did amino acids. 4. 4. Greater incremental increases in the glucosamine radioactivity over amino acids at the longer time intervals suggests that the carbohydrate and protein moieties may have independent metabolic pathways. 5. 5. When Tetrahymena was grown in proteose peptone-tryptone in the presence of labelled amino acid, the specific activity of the surface membrane was less than one-tenth of the specific activity obtained in defined growth media. Under these same conditions, there were only slight changes in the specific activities of glucosamine in the membrane. 6. 6. Data is presented suggesting independent synthesis of the protein and oligosaccharide from different pools.

The purpose of the present communication is to summarize certain of a series of experiments on the partial purification of influenza virus using calcium phosphate as the adsorbing agent. The procedure is simple and the amount of material that can be handled is limited only by the volume of infected lung suspension or chick embryonic tissue suspension available.The procedure herein employed is a modification of a previously reported method1, † for the removal of bacteria from large quantities of broth culture. By the addition of calcium chloride and phosphate buffer, at pH 7.5, a precipitate of calcium phosphate is formed in the broth culture. The precipitate adsorbs the bacteria, settles quickly, and can readily be separated from the supernatant fluid. The bacteria are then “eluted’ from the calcium phosphate by adjusting the hydrogen ion concentration of the resuspended precipitate to about pH 4.5. This causes the calcium phosphate to go into solution, leaving the bacteria suspended in a small volume of ...

1. 1. It has been shown that lysine-ϵ-C 14 , led to a dog, contributes significantly to the biosynthesis of the protoporphyrin IX in erythrocyte hemoglobin. 2. 2. The C 14 -activity of such hemoglobin protoporphyrin was found to be localized largely in carbon atoms C -10 and D -10 as ascertained by isolation of the two carbon atoms in question by means of the Schmidt reaction. 3. 3. A comparison of the specific millimolar C 14 -activities of protoporphyrin IX, and of glutamic and aspartic acids isolated from erythrocyte globin, suggests that the conversion of the carbon skeleton of lysine to the afore-mentioned metabolites occurs without preceding fragmentation through a five carbon intermediary metabolite which may be identical with α-ketoglutarate.

Distribution of added glycine-1-C14 in the perfused dog liver was studied. Concentrations and specific activities of glycine in liver and plasma were measured as a function of time. Calculated values for glycine fluxes between plasma and liver were for influx, 10 to 150, efflux, 10 to 90, and for net influx into liver, –10 to 80 µmole/min/kg liver. Administration of an amino acid mixture containing unlabeled glycine increased the rates of influx, efflux and net flux of glycine into the liver, as well as the concentration of glycine in plasma. The turnover rate of glycine in liver was found to be of the order of 400 µmole/min/kg liver. The specific activities of other amino acids, glucose, and glycogen were measured.

Soy bean nodule homogenates are able to incorporate the carbon atoms of acetate and glycine into hemin. Acids of the Krebs cycle, malonate and sodium azide inhibited the incorporation of the a-carbon atom of glycine into hemin. CoA and substances containing sulfhydryl groups also inhibited the above reaction. Magnesium, acetate, glycine, hydrosulfite and fluoride stimulated. The effects of various combinations of these substances were also investigated. Some implications of the results obtained are discussed.

1. 1. Neural retinas from 7-day chick embryos were dissociated by use of trypsin and oxygen uptake of these dissociated cells was determined micropolarographically. 2. 2. Oxygen consumption was measured from preparations of embryo cells obtained from eggs produced at various times during the year. 3. 3. A value of 4·85 ±0·08 μ 1/min per 10 9 cells was obtained.