Recent trends and open issues in reverse engineering

This paper discusses recent trends in the field of reverse engineering, particularly those highlighted at the Second Working Conference on Reverse Engineering, held in July 1995. The trends observed include increased orientation toward tasks, grounding in complex real-world applications, guidance from empirical study, analysis of non-code sources, and increased formalization. The paper also summarizes open research issues and provides pointers to future events and sources of information in this area.     

Finite sphere packing and sphere covering

A basic problem of finite packing and covering is to determine, for a given number ofk unit balls in Euclideand-spaceE ^d , (1) the minimal volume of all convex bodies into which thek balls can be packed and (2) the maximal volume of all convex bodies which can be covered by thek balls. In the sausage conjectures by L. Fejes Tóth and J. M. Wills it is conjectured that, for alld5, linear arrangements of thek balls are best possible. In the paper several partial results are given to support both conjectures. Furthermore, some relations between finite and infinite (space) packing and covering are investigated.This paper was written while the first named author was visiting the Forschungsinstitut für Geistes- und Sozialwissenschaften at the University of Siegen.     

Automatic absolute determination of total sulfur by combustion and coulometric titration

An automatic method for the absolute determination of total sulfur, which overcomes the tendency of previous methods to give low sulfur recoveries on samples with high oxygen demand, is described. The technique combusts the sample in oxygen and sweeps the combustion gases through a hydrogen peroxide trap to remove the sulfur oxides from the gas stream. The trap contents are volatilized and swept with nitrogen through reduced copper heated to 890 °C. Sulfur oxides are quantitatively converted to sulfur dioxide and titrated coulometrically with iodine. Halogens are held by the copper and do not interfere with the sulfur determination. Analysis time is 12 min and automation of the method allows unattended operation. Sample size is 0.5 to 20 mg. Sulfur levels of 0.05 to 100% can be determined.     

The practical synthesis of a novel and highly potent analogue of bryostatin

Macrocycle 1 is a new highly potent analogue of bryostatin 1, a promising anti-cancer agent currently in human clinical trials. In vitro, 1 displays picomolar affinity for PKC and exhibits over 100-fold greater potency than bryostatin 1 when tested against various human cancer cell lines. Macrocycle 1 can be generated in clinically required amounts by chemical synthesis in only 19 steps (LLS) and represents a new clinical lead for the treatment of cancer.     

Asymmetric hydrogenation of ketones using a ruthenium(II) catalyst containing BINOL-derived monodonor phosphorus-donor ligands

[structure: see text] A series of ruthenium(II) complexes containing BINOL-based monodonor phosphorus ligands have been prepared and applied to the asymmetric catalysis of the hydrogenation of aryl/alkyl ketones. The best ligands for this application are those which contain an aromatic groups with either a methoxide or bromide on the ortho position. Using these ligands, alcohols with ee's of up to 99% are formed.     

In vivo monitoring of skeletal aluminum burden in patients with renal failure

In vivo neutron activation analysis was used to examine the total body and partial body (hand) aluminum levels in patients with end-stage renal failure. Patients maintained on chronic hemodialysis had higher mean body burdens of aluminum than, did those clinically managed without dialysis. Approximately 70% of the patients examined indicated elevated levels of body or skeletal aluminum. A significant correlation was observed between the in vivo aluminum/calcium ratio obtained for the hand measurement and the increase in serum aluminum levels following a disferroxamine infusion test. The direct in vivo monitoring of hand Al/Ca values in patients may provide an alternate choice to bone biopsy for the detection of aluminum intoxication.     

Mass spectrometric study to characterize thioisoindole derivatives of aminoglycoside antibiotics

Aminoglycoside antibiotics are widely used to treat serious Gram-negative and Gram-positive bacterial infections. The lack of a UV chromophore presents a problem in the analysis of aminoglycosides. Derivatization with 1,2-phthalic dicarboxaldehyde (OPA) in the presence of a thiol made it possible to introduce a UV chromophoric thioisoindole moiety. A qualitative mass spectrometry study was carried out to confirm the molecular identity of the products formed. The conditions described earlier to derivatize gentamicin and kanamycin yielded products in which all primary amino groups are fully derivatized. On the other hand, with tobramycin and amikacin, there was also formation of incompletely derivatized products that contained one thioisoindole group less than the fully derivatized product. This study has therefore brought an additional insight into the nature of the OPA-aminoglycoside derivatives studied.     

Toward the molecular flashlight: preparation,properties, and photophysics of a hypericin-luciferin tethered molecule

The synthesis of a molecule containing hypericin and luciferin moieties joined by a tether is reported. The light-induced (in vitro) antiviral activity as well as the photophysical properties of this new compound are measured and compared with those of the parent compounds, hypericin and pseudohypericin. This tethered molecule exhibits excited-state behavior that is very similar to that of its parent compounds and antiviral activity that is identical, within experimental error, to that of its more closely related parent compound, pseudohypericin. The implications for a photodynamic therapy that is independent of external light sources are discussed.