Firm relocation decisions in The Netherlands: An ordered logit approach

This article explores the determinants of firm migration in The Netherlands. First, based on the existing literature a theoretical framework is developed. Second, based on aggregate data firm relocation processes in The Netherlands are discussed in terms of numbers, sectoral composition, origins and destinations (regions), distance moved and employments effects. In the third part a formal model will be tested using individual data of firms. The relocation decisions of individual firms will be related to firm and location characteristics by means of an ordered logit model. The results indicate that the decision to relocate is mainly determined by firm internal factors and to a lesser extent by site related factors. Received 1 July 1999 / Accepted 28 November 1999     

Structure Determination of the Top‐Loop of the Conserved 3′‐Terminal Secondary Structure in the Genome of Flaviviruses

To what extent small differences in RNA sequences (mutations) can have a profound impact on biology remains an intriguing question. This effect can be studied by using untranslated RNA regions as a model. We have studied the influence of mutations on the structure of an RNA hairpin that occurs in the 3′‐untranslated region (UTR) of Flaviviridae, and is known to have a large impact on the vector dependency of flaviviruses. Three related RNA sequences were studied by NMR spectroscopy. The selected sequences represent each one of the three clusters in the flavivirus genes (mosquito‐borne, tick‐borne, and no‐known‐vector viruses). A new strategy was used to obtain chemical shift signatures of carbonyl atoms in unlabeled uridine nucleobases to characterize their involvement in hydrogen bonding. Clear differences occur in the structures and stacking pattern of the three RNA hairpins. The observed differences cannot be predicted based on sequence analysis. A different biology can be correlated with a different RNA tertiary structure. The underlying biological mechanism, however, remains to be studied.     

Film Thickness of Mechanically Worked Lubricating Grease at Very Low Speeds

Several different types of commercially available greases, aged in a roll stability tester, have been tested in a ball-on-disc machine where the film thickness was measured using the interferometry method. The grease film thickness at very low speed is thicker than the base oil film thickness due to the contribution of the thickener in this regime, which practically vanishes at higher speeds. The (mechanical) aging process reduces the thickener material, decreasing the grease film thickness at very low speeds (entrainment speed less than 0.01 m/s) with aging time, whereas no significant difference was found at higher speeds where the grease film thickness still approached the calculated base oil film thickness.     

Discovery of an Acyclic Nucleoside Phosphonate that Inhibits Mycobacterium tuberculosis ThyX Based on the Binding Mode of a 5‐Alkynyl Substrate Analogue

The urgent need for new antibiotics poses a challenge to target un(der)exploited vital cellular processes. Thymidylate biosynthesis is one such process due to its crucial role in DNA replication and repair. Thymidylate synthases (TS) catalyze a crucial step in the biosynthesis of thymidine 5‐triphosphate (TTP), an elementary building block required for DNA synthesis and repair. To date, TS inhibitors have only been successfully applied in anticancer therapy due to their lack of specificity for antimicrobial versus human enzymes. However, the discovery of a new family of TS enzymes (ThyX) in a range of pathogenic bacteria that is structurally and biochemically different from the “classic” TS (ThyA) has opened the possibility to develop selective ThyX inhibitors as potent antimicrobial drugs. Here, the interaction of the known inhibitor 5‐(3‐octanamidoprop‐1yn‐1yl)‐2′‐deoxyuridine‐5′‐monophosphate ( 1 ) with Mycobacterium tuberculosis ThyX enzyme is explored using molecular modeling starting from published crystal structures, with further confirmation through NMR experiments. While the deoxyuridylate (dUMP) moiety of compound 1 occupies the cavity of the natural substrate in ThyX, the rest of the ligand (the “5‐alkynyl tail”) extends to the outside of the enzyme between two of its four subunits. The hydrophobic pocket that accommodates the alkyl part of the tail is formed by displacement of Tyr 44.C, Tyr 108.A and Lys 165.A. Changes to the resonance of the Lys 165 NH₃ group upon ligand binding were monitored in a titration experiment by 2D HISQC NMR. Guided by the results of the modeling and NMR studies, and inspired by the success of acyclic antiviral nucleosides, compounds where a 5‐alkynyl uracyl moiety is coupled to an acyclic nucleoside phosphonate (ANP) were synthesized and evaluated. Of the compounds evaluated, sodium (6‐(5‐(3‐octanamidoprop‐1‐yn‐1‐yl)‐2,4‐dioxo‐3,4‐dihydropyrimidin‐1(2H)‐yl)hexyl)phosphonate ( 3 e ) exhibited 43 % of inhibitory effect on ThyX at 50 μM . While only modest activity was achieved, this is the first example of an ANP inhibiting ThyX, and these results can be used to further guide structural modifications to this class to develop more potent compounds with potential application as antibacterial agents acting through a novel mechanism of action.     

On the relationship between travel time and travel distance of commuters

This paper gives a detailed empirical analysis of the relationships between different indicators of costs of commuting trips by car: difference as the crow flies, shortest travel time according to route planner, corresponding travel distance, and reported travel time. Reported travel times are usually rounded in multiples of five minutes. This calls for special statistical techniques. Ignoring the phenomenon of rounding leads to biased estimation results for shorter distances. Rather surprisingly, the distance as the crow flies and the network distance appear to be slightly better proxies of the reported travel time compared with the shortest network travel time as indicated by the route planner. We conclude that where actual driving times are missing in commuting research the other three indicators mentioned may be used as proxies, but that the following problems may emerge: actual travel times may be considerably higher than network times generated by route planners, and the average speed of trips increases considerably with distance, implying an overestimate of travel time for long distance commuters. The only personal feature that contributes significantly to variations in reported travel times is gender: women appear to drive at lower average speeds according to our data. As indicated in the paper this may be explained by the differences in the car types of male and female drivers (females drive older and smaller cars) as well as higher numbers of stops/trip chaining among women. A concise analysis is carried out for carpoolers. Car-pooling leads to an increase in travel time of some 17% compared with solo drivers covering the same distance. In the case of car poolers, the above mentioned measures appear to be very poor proxies for the actual commuting times. Received: November 1996/Accepted: January 1998     

Real-Time Fetal ECG Recording

We present a real-time abdominal recording method for the FECG based on a minimization procedure for the MECG interference, by weighted addition of four abdominal leads containing FECG with a large amount of MECG. The minimization of the MECG does not influence the FECG recording adversely. FECG complexes coinciding with MECG complexes are also recorded. Use is made of programmable amplifiers that multiply analog abdominal leads by digital coefficients. These coefficients are calculated at the beginning of the recording by a microcomputer system. Experimental results are shown that clarify the advantages of the measurement principle. The real-time recorded FECG is wide-banded, so that all generally known ECG signal processing techniques, such as complex averaging, can be performed.     

STABLE ALGORITHMS FOR THE STATE SPACE MODEL

Abstract. Numerically stable algorithms are developed for filtering, likelihood evaluation, generalized least squares computation and smoothing where data are generated by a state space model. The algorithms handle diffuse initial states in a numerically safe way. Singular innovation covariance matrices, such as those which arise in series with missing values, are dealt with. The algorithms generalize stable algorithms for ordinary least-squares computations.     

Influence of the molecular weight of ionenes on the cobaltphthalocyanine-catalysed autoxidation of mercaptoethanol

In order to study the promoting effect of polycations on the cobalt(II)phthalocyanine-tetrasodiumsulphonate (CoPc(NaSO₃)₄)-catalysed autoxidation of thiols, it is imperative to know the molecular weight dependence of the polymer. Monodisperse oligomers can often supply a lot of information. To elecidate the mechanism of the promoting effect of 2,4-ionene, a poly(quaternary ammonium)salt, on the CoPc(NaSO₃)₄-catalysed autoxidation of 2-mercaptoethanol, a series of monodisperse 2,4-ionene oligomers were prepared. Trimeric 2,4-ionenes, containing two quaternary ammonium groups separated by four methylene groups, showed a high co-catalytic activity, and active Co-aggregates were detected with visible light spectroscopy. The spectroscopic behaviour was in close agreement with that of high molecular 2,4-ionene/CoPc(NaSO₃)₄ complexes. In order to achieve this aggregation several oligomeric ionenes have to act concertedly. If the distance between the ionic sites is short the trimer acts as a simple salt in stablizing the aggregates. With respect to the catalytic activity the optimum polycation/catalyst ratio, expressed as the N⁺/Co ratio, decreased with increasing chain lenght and reached a constant level of 50 at a 2,4-ionene nonamer. For the trimers and pentamers this ratio is affected by the type of end-group. All synthesized 2,4-ionene oligomers exhibited excellent co-catalytic properties at the optimum N⁺/Co ratio, with maximum turnover frequencies of 4600 mol thiol/(mol Co s), i.e. 50 times higher than those obtained for the polymer-free system. In the case of monodisperse 2,4-ionene pentamer with bromo end-groups, double Michaelis–Menten kinetics were observed, as also was exhibited by high molecular weight ionene.     

Probing Ambiguous Base‐Pairs by Genetic Transformation with XNA Templates

The templating potential of anhydrohexitol oligonucleotides bearing ambiguous bases was studied in vivo, by using a selection screen for mosaic heteroduplex plasmids in Escherichia coli. 1,5‐Anhydro‐2,3‐dideoxy‐2‐(5‐nitroindazol‐1‐yl)‐D ‐arabino‐hexitol showed the greatest ambiguity among the three nucleosides tested. At most two successive ambiguous bases could be tolerated on hexitol templates read in bacterial cells. Hexitol nucleosides bearing simplified heterocycles thus stand as promising monomers for generating random DNA sequences in vivo from defined synthetic oligonucleotides.