A germaaluminocene

The reactions of dipotassium germacyclopentadienediide with two Group 13 dichlorides, Cp*BCl₂ and Cp*AlCl₂, yield two structurally different products. In the case of boron a borole complex of germanium(ii) is obtained. The aluminium halide gives an unprecedented neutral germaaluminocene. Both compounds were fully characterised by multinuclear NMR spectroscopy supported by DFT computations. The molecular structure of the germaaluminocene was determined by XRD.

Boron vs. aluminum: the synthesis of a borole complex of Ge(ii) is reported. Changing just the element from boron to aluminum unexpectedly yields an unprecedented neutral germaaluminocene.     

Anodic growth of self-ordered magnesium oxy-fluoride nanoporous/tubular layers on Mg alloy (WE43)

In the present work we show that self-ordered nanotubular and nanoporous magnesium oxy-fluoride structures can be grown on a magnesium-based alloy when anodized in a non-aqueous (ethylene glycol) HF electrolyte. The morphology of the surface structures varies with applied potential and anodisation time. Tubular and porous structures with different sizes and orientation can be grown.     

Inventory problems with perishable items: Fixed lifetimes and backlogging

Our model deals with a single-product and a single-stock location with Poisson demand. The replenishment leadtime from the external supplier is fixed. The lifetime of the product is also fixed, and aging is assumed to begin when the order is placed. When the age of a unit has reached its lifetime, the unit is useless and thus discarded from the system. The replenishment policy is assumed to be an order-up-to S-policy. Demand that cannot be met immediately is backordered. We consider three different cases where the service requirements are represented by: (1) backorder costs per unit, (2) a service level constraint, (3) backorder costs per unit and time unit. Cases 1 and 2 are solved exactly, while an approximation is developed for case 3. We show how the results from an earlier paper assuming lost sales can be used to solve the considered problems. Our results are compared to the results in a related paper considering (Q, r)-policies.     

Site-Specific Radioiodination of HER2-Targeting Affibody Molecules using 4-Iodophenethylmaleimide Decreases Renal Uptake of Radioactivity

Affibody molecules are small scaffold-based affinity proteins with promising properties as probes for radionuclide-based molecular imaging. However, a high reabsorption of radiolabeled Affibody molecules in kidneys is an issue. We have shown that the use of ¹²⁵I-3-iodo-((4-hydroxyphenyl)ethyl)maleimide (IHPEM) for site-specific labeling of cysteine-containing Affibody molecules provides high tumor uptake but low radioactivity retention in kidneys. We hypothesized that the use of 4-iodophenethylmaleimide (IPEM) would further reduce renal retention of radioactivity because of higher lipophilicity of radiometabolites. An anti-human epidermal growth factor receptor type 2 (HER2) Affibody molecule (Z_HER2:2395) was labeled using ¹²⁵I-IPEM with an overall yield of 45±3 %. ¹²⁵I-IPEM-Z_HER2:2395 bound specifically to HER2-expressing human ovarian carcinoma cells (SKOV-3 cell line). In NMRI mice, the renal uptake of ¹²⁵I-IPEM-Z_HER2:2395 (24±2 and 5.7±0.3 % IA g⁻¹at 1 and 4 h after injection, respectively) was significantly lower than uptake of ¹²⁵I-IHPEM-Z_HER2:2395 (50±8 and 12±2 % IA g⁻¹at 1 and 4 h after injection, respectively). In conclusion, the use of a more lipophilic linker for the radioiodination of Affibody molecules reduces renal radioactivity.     

A component tracking algorithm for accelerated and improved liquid chromatography-mass spectrometry method development

A method for tracking of sample components during liquid chromatography-mass spectrometry (LC-MS) method development has been proposed. The method manages to, fully automatically and without user intervention, find the chromatographic peaks in the data sets, discriminate them to sample components and track them when the separation conditions have been changed. The algorithm utilises the resolution obtained from all considered data sets and has the ability to discriminate the non informative parts. The technique has a great sensitivity even in cases where a majority of the tracked components cannot easily be spotted by means of traditional total ion chromatogram (TIC) or base peak chromatogram (BPC) representations. The method was tested on an experimental sample using six different columns and an average of 79% of the suggested sample components could be successfully tracked at a minimum area of 0.05% of the main component in the sample. 66 components with 79-92% of the total suggested component area were able to be tracked between all data sets. The method could be used to rapidly investigate selectivity during different types of separation conditions.     

Electrospray ionization mass spectrometry from discrete nanoliter‐sized sample volumes

We describe a method for nanoelectrospray ionization mass spectrometry (nESI‐MS) of very small sample volumes. Nanoliter‐sized sample droplets were taken up by suction into a nanoelectrospray needle from a silicon microchip prior to ESI. To avoid a rapid evaporation of the small sample volumes, all manipulation steps were performed under a cover of fluorocarbon liquid. Sample volumes down to 1.5 nL were successfully analyzed, and an absolute limit of detection of 105 attomole of insulin (chain B, oxidized) was obtained. The open access to the sample droplets on the silicon chip provides the possibility to add reagents to the sample droplets and perform chemical reactions under an extended period of time. This was demonstrated in an example where we performed a tryptic digestion of cytochrome C in a nanoliter‐sized sample volume for 2.5 h, followed by monitoring the outcome of the reaction with nESI‐MS. The technology was also utilized for tandem mass spectrometry (MS/MS) sequencing analysis of a 2 nL solution of angiotensin I. Copyright © 2010 John Wiley & Sons, Ltd.     

Separation and characterization of aggregated species of amyloid-beta peptides

We have investigated the use of isoelectric focusing and immunodetection for the separation of low molecular weight species of amyloid-beta (Aβ) peptides from their aggregates. From solutions of Aβ_1–40 or Aβ_1–42 monomeric peptides, low molecular weight material appeared at a pI value of ca. 5, while the presence of aggregates was detected as bands, observed at a pI of 6–6.5. The formation of Aβ aggregates (protofibrils) was verified by a sandwich ELISA, employing the protofibril conformation-selective antibody mAb158. In order to study the aggregation behavior when using a mixture of the monomers, we utilized the IEF separation combined with Western blot using two polyclonal antisera, selective for Aβ_1–40 and Aβ_1–42, respectively. We conclude that both monomers were incorporated in the aggregates. In a further study of the mixed aggregates, we used the protofibril conformation-selective antibody mAb158 for immunoprecipitation, followed by nanoelectrospray mass spectrometry (IP-MS). This showed that the Aβ_1–42 peptide is incorporated in the aggregate in a significantly larger proportion than its relative presence in the original monomer composition. IP-MS with mAb158 was also performed, and compared to IP-MS with the Aβ-selective antibody mAb1C3, where a monomeric Aβ_1–16 peptide was added to the protofibril preparation. Aβ_1–16 is known for its poor aggregation propensity, and acted therefore as a selectivity marker. The results obtained confirmed the protofibril conformation selectivity of mAb158.     

Influence of weakly bound adduct ions on breath trace gas analysis by selected ion flow tube mass spectrometry (SIFT-MS)

This paper describes how weakly bound adduct ions form when the precursor ions used in selected ion flow mass spectrometry, SIFT-MS, analyses, viz. H₃O⁺, NO⁺ and O₂⁺, associate with the major components of air and exhaled breath, N₂, O₂ and CO₂. These adduct ions, which include H₃O⁺N₂, H₃O⁺CO₂, NO⁺CO₂, O₂⁺O₂ and O₂⁺CO₂, are clearly seen when dry air containing 5% CO₂ (typical of that in exhaled breath) is analysed using SIFT-MS. These adduct ions must not be misinterpreted as characteristic product ions of trace gases; if so, serious analytical errors can result. However, when exhaled breath is analysed these adduct ions are partly removed by ligand switching reactions with the abundant water molecules and the problems they represent are alleviated. But the small fractions of the adduct ions that remain in the SIFT-MS spectra, and especially when they are isobaric with genuine characteristic product ion of breath trace gases, can result in erroneous quantifications; such is the case for H₃O⁺N₂ interfering with breath ethanol analysis and H₃O⁺CO₂ with breath acetaldehyde analysis. However, these difficulties can be overcome when the isobaric adduct ions are properly recognised and excluded from the analyses; then these two important compounds can be properly quantified in breath. The presence of O₂⁺CO₂ in the product ion spectra interferes with the analysis of CS₂ present at low levels in exhaled breath. It is likely that similar problems will occur as other trace compounds are detected in exhaled breath when consideration will have to be given to the possibility of overlapping between their characteristic product ions and ions produced by hitherto unknown reactions. Similar problems are evident in other systems; for example, H₃O⁺CH₄ adduct ions are observed in both SIFT-MS analyses of methane rich mixtures like biologically generated waste gases and in model planetary atmospheres.