Discovery of α‐Substituted Imidazole‐4‐acetic Acid Analogues as a Novel Class of ρ1 γ‐Aminobutyric Acid Type A Receptor Antagonists with Effect on Retinal Vascular Tone

The ρ‐containing γ‐aminobutyric acid type A receptors (GABA_ARs) play an important role in controlling visual signaling. Therefore, ligands that selectively target these GABA_ARs are of interest. In this study, we demonstrate that the partial GABA_AR agonist imidazole‐4‐acetic acid (IAA) is able to penetrate the blood–brain barrier in vivo; we prepared a series of α‐ and N‐alkylated, as well as bicyclic analogues of IAA to explore the structure–activity relationship of this scaffold focusing on the acetic acid side chain of IAA. The compounds were prepared via IAA from l ‐histidine by an efficient minimal‐step synthesis, and their pharmacological properties were characterized at native rat GABA_ARs in a [³H]muscimol binding assay and at recombinant human α₁β₂γ_2S and ρ₁ GABA_ARs using the FLIPR? membrane potential assay. The (+)‐α‐methyl‐ and α‐cyclopropyl‐substituted IAA analogues ((+)‐ 6 a and 6 c , respectively) were identified as fairly potent antagonists of the ρ₁ GABA_AR that also displayed significant selectivity for this receptor over the α₁β₂γ_2S GABA_AR. Both 6 a and 6 c were shown to inhibit GABA‐induced relaxation of retinal arterioles from porcine eyes.     

Safety against formation of through cracks of profiled fibre-reinforced cement sheets for roofing

Loads due to wind, snow or traffic on a roof determine the requirements to the strength and stiffness properties of profiled sheets for roofing. Apart from these loads, locked-in stresses can occur due to differences in temperature and moisture strains in the profiled sheets and the wooden laths supporting the sheets. These tensile and compressive stresses are induced in the sheets if they are firmly fastened to the laths with fastening screws.The purpose of this investigation was to analyse the safety of the profiled sheets in transmitting these loads without the formation of through cracks.The analysis is based on an experimental and a theoretical investigation of the strength and stiffness properties of unexposed profiled fibre-reinforced cement sheets and of sheets that had been exposed on a roof in three years.     

Test-retest reliability and concurrent validity of a web-based questionnaire measuring workstation and individual correlates of work postures during computer work

INTRODUCTION: "Ergonomic" questionnaires are widely used in epidemiological field studies to study the association between workstation characteristics, work posture and musculoskeletal disorders among office workers. Findings have been inconsistent regarding the putative adverse effect of work postures. Underestimation of the true association might be present in studies due to misclassification of subjects to risk (i.e. exposed to non-neutral working postures) and no-risk categories (i.e. not exposed to non-neutral working postures) based on questionnaire responses. The objective of this study was to estimate the amount of misclassification resulting from the use of questionnaires. METHODS: Test-retest reliability and concurrent validity of a newly developed questionnaire was assessed. This questionnaire collects data on workstation characteristics and on individual characteristics during computer work (i.e. work postures, movements and habits). Pictures were added where possible to provide visual guidance. The study population consisted of 84 office workers of a research department. They filled out the questionnaire on the Internet twice, with an in-between period of 2 weeks. For a subgroup of workers (n=38), additional on-site observations and multiple manual goniometer measurements were performed. RESULTS: Percentage agreement ranged between 71% and 100% for the test-retest analysis, between 31% and 100% for the comparison between questionnaire and on-site observation, and between 26% and 71% for the comparison between questionnaire and manual goniometer measurements. For 9 out of 12 tested items, the percentage agreement between questionnaire and manual goniometer measurements was below 50%. CONCLUSIONS: The questionnaire collects reliable data on workstation characteristics and some individual characteristics during computer work (i.e. work movements and habits), but does not seem to be useful to collect data on work postures during computer work in epidemiological field studies among office workers.     

Does musculoskeletal discomfort at work predict future musculoskeletal pain?

The objective of this prospective cohort study was to evaluate if peak or cumulative musculoskeletal discomfort may predict future low-back, neck or shoulder pain among symptom-free workers. At baseline, discomfort per body region was rated on a 10-point scale six times during a working day. Questionnaires on pain were sent out three times during follow-up. Peak discomfort was defined as a discomfort level of 2 at least once during a day; cumulative discomfort was defined as the sum of discomfort during the day. Reference workers reported a rating of zero at each measurement. Peak discomfort was a predictor of low-back pain (relative risk (RR) 1.79), neck pain (RR 2.56), right or left shoulder pain (RR 1.91 and 1.90). Cumulative discomfort predicted neck pain (RR 2.35), right or left shoulder pain (RR 2.45 and 1.64). These results suggest that both peak and cumulative discomfort could predict future musculoskeletal pain.     

A method of measuring oil consumption by labelling with radioactive bromine

A method of determining the oil consumption rate of combustion engines is presented. It is based on labelling the individual oil fractions of engine oil with radioactive bromine isotope⁸² Br and on the quantitative absorption of radioactive bromine compounds in the exhaust gas in an aqueous solution of nitric acid and silver nitrate. The advantages of this method are that the oil that is consumed in the exhaust gas can be directly measured, without the fluctuating amounts of oil in the sump influencing the result, and the behaviour of the individual components of the oil in the consumption process can be determined. The test is quick, only twenty minutes being required to detect oil consumption at one operating point; and with a single labelling, the oil consumption at a great number of working engine points can be measured ⁸² Br has a short half‐life of only 36 h, so that compliance with radiation protection measures is inexpensive and investigations can be carried out using a conventional testing device. As part of the research project, a study was made of the influence of different base oil types, with and without polymer additives, on consumption. Results showed that Noack evaporation loss correlated with oil consumption only with boiling fractions of exactly the same base oil, and not with different, in particular synthetic, base oils; that polymer additives (VI improvers) significantly reduced the rate of oil consumption; and that the polymer additive and the type of base oil both had more influence on oil consumption than viscosity.     

Formation of white spots in the shell of raw shrimps during frozen storage. Seasonal variation and effects of some production factors

During frozen storage of raw pink shrimps, Pandalus borealis, calcium carbonate tends to precipitate in the exoskeleton, giving the shrimps a spotted appearance. Seasonal variations in the formation of white spots and the influence of shrimp size, production time, chemical treatment, and storage temperature on white spot formation was determined. A significant effect (P=0·003) of day of catch was observed and shrimps caught in the summer period showed a greater tendency of white spot formation than shrimps caught during the rest of the year. Treatment in a sulphite, a phosphate or a phthalate solution prior to freezing retards calcium carbonate crystallisation (P<0·05) while treatment in a borax solution promotes crystallisation (P<0·05). Prolonged time from catch to chemical treatment and increased storage time increase the risk of white spot formation. Storage temperature has a significant effect on white spot formation for which process the rate at different temperatures was described by the Arrhenius equation with a high energy of activation of 90 kJ mol⁻¹. The size (age) of the shrimps did not influence white spot formation (P=0·69). From these findings it is concluded that calcium carbonate precipitation resulting in white spots in shrimp shell can be retarded or possibly prevented by short production time, appropriate chemical treatment and very low storage temperature. ©1997 SCI     

Site of alkylation in pyrimidine derivatives: Studies on the structure of 1-Alkyl-4-amino-6-methylpyrimidinium Iodides

The alkylation of 4-amino-6-methylpyrimidines ( 1a-f ) in DMSO or nitrobenzene at room temperature affords the ¹N-alkylated products 2a-h . Treatment of 1a-c with an excess of methyl iodide in the presence of powdered alkali metal hydroxides/DMSO gives the pyrimidinium salts 2g , i , j. Carbon-13 n.m.r. and X-ray studies have shown that in the case of compounds 2 the polymethine structure B is preferred.     

Detection of seven virulence and toxin genes of Campylobacter jejuni isolates from Danish turkeys by PCR and cytolethal distending toxin production of the isolates

A total of 117 Campylobacter jejuni isolates from Danish turkeys were tested for the presence of seven virulence and toxin genes by PCR. One hundred seventeen (100%) isolates were positive for flaA, cadF, and ceuE gene primers. One hundred three (88%) isolates were positive for cdt gene cluster PCR detection (cdt gene cluster-PCR), whereas 101 (86.3%), 102 (87.2%), and 110 (94%) isolates were positive for cdtA-, cdtB-, and cdtC-PCR, respectively. Only 39 (33.3%) isolates were positive for virB11. Of 117 isolates, 114 (97.4%) produced cytolethal distending toxin (CDT) in Vero cell assays, 105 (89.7%) in Colon 205 assays, and 109 (93.2%) in chicken embryo cell assays. The CDT titers were determined in Vero cell assays. Of 117 isolates, 50 (42.7%) produced a CDT titer of 1:100, 29 (24.8%) of 1:50, and 27 (23%) of 1:5 to 1:10; 8 (6.8%) produced a CDT titer at undiluted supernatants and 3 (2.6%) produced no toxin. Twenty-nine C. jejuni isolates that were PCR negative for one or more individual cdt toxin genes also produced low or no CDT toxin. The high prevalence of the seven virulence and toxin genes demonstrates that these putative pathogenic determinants are widespread among Campylobacter isolates from turkeys and calls for further investigation for the elimination of Campylobacter infection in industrial turkey production and in industrial food chains.     

A fuzzy logic pitch angle controller for power system stabilization

In this article the design of a fuzzy logic pitch angle controller for a fixed speed, active‐stall wind turbine, which is used for power system stabilization, is presented. The system to be controlled, which is the wind turbine and the power system to which the turbine is connected, is described. The advantages of fuzzy logic control when applied to large‐signal control of active‐stall wind turbines are outlined. The general steps of the design process for a fuzzy logic controller, including definition of the controller inputs, set‐up of the fuzzy rules and the method of defuzzification, are described. The performance of the controller is assessed by simulation, where the wind turbine's task is to dampen power system oscillations. In the scenario simulated for this work, the wind turbine has to ride through a transient short‐circuit fault and subsequently contribute to the damping of the grid frequency oscillations that are caused by the transient fault. It is concluded that the fuzzy logic controller enables the wind turbine to dampen power system oscillations. It is also concluded that, owing to the inherent non‐linearities in a wind turbine and the unpredictability of the whole system, the fuzzy logic controller is very suitable for this application. Copyright © 2006 John Wiley &Sons, Ltd.