Dynamic programming based algorithms for the discounted {0-1} knapsack problem

The discounted {0-1} knapsack problem (DKP) is an extension of the classical {0-1} knapsack problem (KP) that consists of selecting a set of item groups where each group includes three items and at most one of the three items can be selected. The DKP is more challenging than the KP because four choices of items in an item group diversify the selection of the items. Consequently, it is not possible to solve the DKP based on a classical definition of a core consisting of a small number of relevant variables. This paper partitions the DKP into several easier sub-problems to achieve problem reductions by imitating the core concept of the KP to derive an alternative core for the DKP. Numerical experiments with DP-based algorithms are conducted to evaluate the effectiveness of the problem partition by solving the partitioned problem and the original problem based on different types of DKP instances.     

Genetic Encoding of bicyclononynes and trans-cyclooctenes for site-specific protein labeling in vitro and in live mammalian cells via rapid fluorogenic Diels-Alder reactions

Rapid, site-specific labeling of proteins with diverse probes remains an outstanding challenge for chemical biologists. Enzyme-mediated labeling approaches may be rapid but use protein or peptide fusions that introduce perturbations into the protein under study and may limit the sites that can be labeled, while many "bioorthogonal" reactions for which a component can be genetically encoded are too slow to effect quantitative site-specific labeling of proteins on a time scale that is useful for studying many biological processes. We report a fluorogenic reaction between bicyclo[6.1.0]non-4-yn-9-ylmethanol (BCN) and tetrazines that is 3-7 orders of magnitude faster than many bioorthogonal reactions. Unlike the reactions of strained alkenes, including trans-cyclooctenes and norbornenes, with tetrazines, the BCN-tetrazine reaction gives a single product of defined stereochemistry. We have discovered aminoacyl-tRNA synthetase/tRNA pairs for the efficient site-specific incorporation of a BCN-containing amino acid, 1, and a trans-cyclooctene-containing amino acid 2 (which also reacts extremely rapidly with tetrazines) into proteins expressed in Escherichia coli and mammalian cells. We demonstrate the rapid fluorogenic labeling of proteins containing 1 and 2 in vitro, in E. coli , and in live mammalian cells. These approaches may be extended to site-specific protein labeling in animals, and we anticipate that they will have a broad impact on labeling and imaging studies.     

Site-specific traceless coupling of potent cytotoxic drugs to recombinant antibodies for pharmacodelivery

Aldehyde drugs are gaining increasing research interest, considering that aldehyde dehydrogenases overexpression is characteristic of cancer stem cells. Here, we describe the traceless site-specific coupling of a novel potent drug, containing an aldehyde moiety, to recombinant antibodies, which were engineered to display a cysteine residue at their N-terminus, or a 1,2-aminothiol at their C-terminus. The resulting chemically defined antibody-drug conjugates represent the first example in which a thiazolidine linkage is used for the targeted delivery and release of cytotoxic agents.     

Localization and tensorization properties of the curvature-dimension condition for metric measure spaces

This paper is devoted to the analysis of metric measure spaces satisfying locally the curvature-dimension condition CD(K,N) introduced by the second author and also studied by Lott & Villani. We prove that the local version of CD(K,N) is equivalent to a global condition CD^∗(K,N), slightly weaker than the (usual, global) curvature-dimension condition. This so-called reduced curvature-dimension condition CD^∗(K,N) has the local-to-global property. We also prove the tensorization property for CD^∗(K,N). As an application we conclude that the fundamental group π₁(M,x₀) of a metric measure space (M,d,m) is finite whenever it satisfies locally the curvature-dimension condition CD(K,N) with positive K and finite N.     

Photoelectron emission spectroscopy of liquid water

The threshold energy E_t = 10.06 eV (0.002 eV standard deviation) is determined for photoelectron emission by liquid water and is correlated with E_t = 8.45 eV for OH^? (aq). Free energy changes and standard reduction potentials are calculated for both emission processes. Reorganization free energies are correlated to solvation free energies for H₂O⁺(aq) and OH^?(aq).     

Bioaerosol analysis based on a label-free microarray readout method using surface-enhanced Raman scattering

Bacterial contamination of indoor air is a serious threat to human health. Pathogenic germs can be transferred from the liquid to the aerosol phase, for instance, when water is sprayed in the air, such as in shower rooms, air conditioners, or fountains. Existing analytical methods for biological indoor air-quality assessment and contamination monitoring are mostly time consuming as they generally require a cultivation step. The need for a rapid, sensitive, and selective detection method for bioaerosols is evident. Our approach is based on the combination of a commercial wet particle sampler (Coriolis μ, Bertin Technologies, France) and a label-free microarray readout based on surface-enhanced Raman scattering (SERS) for detection, which was established in our laboratories. Heat-inactivated Escherichia coli bacteria were used as test microorganisms. An E. coli suspension was sprayed into the chamber by a jet air nebulizer. The resulting bioaerosol was dried, neutralized, and then collected by a Coriolis μ sampler. The bacteria collected were detected by a recently developed microarray readout system, based on label-free SERS detection. A special data evaluation procedure was applied in order to fully exploit the selectivity of the detection scheme, resulting in a detection limit of 144 particles per cubic centimeter.     

Catalytic mechanism of limonene epoxide hydrolase, a theoretical study

The catalytic mechanism of limonene epoxide hydrolase (LEH) was investigated theoretically using the density functional theory method B3LYP. LEH is part of a novel limonene degradation pathway found in Rhodococcus erythropolis DCL14, where it catalyzes the hydrolysis of limonene-1,2-epoxide to give limonene-1,2-diol. The recent crystal structure of LEH was used to build a model of the LEH active site composed of five amino acids and a crystallographically observed water molecule. With this model, hydrolysis of different substrates was investigated. It is concluded that LEH employs a concerted general acid/general base-catalyzed reaction mechanism involving protonation of the substrate by Asp101, nucleophilic attack by water on the epoxide, and abstraction of a proton from water by Asp132. Furthermore, we provide an explanation for the experimentally observed regioselective hydrolysis of the four stereoisomers of limonene-1,2-epoxide.     

Analytical evidence of amorphous microdomains within nitridosilicate and nitridoaluminosilicate single crystals

Single crystals of new nitridosilicates and nitridoaluminosilicates with excellent R values in X-ray investigations were analysed quantitatively using 30 to 60 μm single-spot LA-ICP-MS. Significant discrepancies between expected and measured chemical composition could not be explained by the crystallographic data. High spatial resolution analysis using electron probe microanalysis (EPMA, 10 μm) leads to the discovery of inhomogeneities in the crystalline material. The application of standard single-spot LA-ICP-MS with a spatial resolution of 30 to 60 μm is not suitable for the analysis of these crystals as the existing inhomogeneities dominate and alter the determined concentrations. However, owing to the better detection capabilities, a scanning LA-ICP-MS procedure enables a more representative analysis of single crystals of Ca₅Si₂Al₂N₈ than single-spot LA-ICP-MS as a result of a larger sampling volume. It is highly likely that these impurities consist of amorphous, vitreous phases as powder diffraction X-ray data indicates the existence of a significant fraction of an X-ray amorphous material besides crystalline silicates. These microdomains contain less aluminium, silicon and calcium or are nearly free of aluminium, which explains the detected discrepancies in the chemical composition.     

Validation of standardized high-performance thin-layer chromatographic methods for quality control and stability testing of herbals

In herbal medicinal products the entire herbal drug or an herbal drug preparation is regarded as the active pharmaceutical ingredient, regardless of whether constituents with defined therapeutic activity are known. In quality control and stability testing of herbal medicinal products, fingerprint chromatograms are used as powerful tools to evaluate and compare the composition of compounds in such products. To fulfill the International Conference on Harmonization and Good Manufacturing Practice-based regulatory requirements in pharmaceutical quality control, chromatographic fingerprint analysis needs to be validated. Based on a standardized methodology, this paper provides a comprehensive concept for evaluating validation parameters for planar chromatographic fingerprinting by considering the stationary phase, sample application, developing solvent, chromatogram development, plate labeling, derivatization, documentation, and chromatographic equipment. Validation parameters addressed include stability of the analyte, selectivity, robustness testing, and method reproducibility.     

Oxydation von14C-kernmarkiertem Bikreosol in wäßrig-alkalischer Lösung mit Sauerstoff

Bicreosol, labelled in different ring positions (2.2′ or 3.3′ or 6.6′) with¹⁴C, was oxygenated in 0.25m-NaOH at 70°. A number of low molecular fragments was isolated and their specific activities were determined. It was possible to show, that most of the isolated acetone, formed by ring splitting, originates from ring-C-atoms 4 and 5 and the methyl group; the largest part of the isolated oxalic acid (formed in relatively small amounts) derives from ring-C-atoms 2 and 3, which are mainly split off as CO₂.