Log-scale dose response of inhibitors on a chip

We demonstrate the accommodation of log-scale concentration gradients of inhibitors on a single microfluidic chip with a semidirect dilution capability of reagents for the determination of the half-inhibitory concentration or IC(50). The chip provides a unique tool for hosting a wide-range of concentration gradient for studies that require an equal distribution of measuring points on a logarithmic scale. Using Matrix metalloproteinase IX and three of its inhibitors, marimastat, batimastat, and CP471474, we evaluated the IC(50) of each inhibitor with a single experiment. The present work could be applied to the systematic study of biochemical binding and inhibition processes particularly in the field of mechanistic enzymology and the pharmaceutical industry.     

Searching? Or actually trying to find something? – The comforts of searching versus the challenges of finding

Every information professional has a unique way of conducting searches depending on his or her mindset. At one end of the spectrum there are those professionals that focus on the process of searching; At the other end there are those that focus on the objective of finding. This may seem to be a trivial distinction, as the process of searching should naturally be directed at finding relevant documents. However, this article illustrates that these different mindsets are in fact real and that they have a significant effect on the way searches are being conducted.Information professionals focussing on the process of searching enjoy the relative comfort of structure provided by the use of guidelines and checklists whereas professionals focussing on the objective of finding are willing to treat each search as a unique puzzle that requires a unique solution not bounded by guidelines or instructions.In this article the merits of both mindsets are discussed.The article is based on the author’s experience in the engineering field. Therefore some of the arguments set forth may be less relevant in for instance the chemical or biotechnology fields.     

Effect of dietary forage:grain ratio on blood constituents in dairy cows

Forty-nine primiparous and 44 multiparous lactating Holstein cows were used to study the effect of five dietary forage: grain ratios on blood constituents. Blood samples were collected in wk 2, 3, 4, 6, 8, 12, and 16 of lactation and were analyzed for glucose, urea, beta-hydroxybutyrate, and FFA. Increasing the percentage of forage in the diet decreased blood glucose concentration. Glucose levels were low at the beginning of lactation and increased as DMI increased. Increasing percentage of forage in the diet did not affect blood urea concentration. Increasing forage in the diet from 38.2 to 98.2% increased beta-hydroxybutyrate concentrations threefold during the first 4 wk of lactation in both primiparous and multiparous cows. The concentration of plasma FFA was higher in all the treatments at the beginning of lactation and decreased as lactation advanced. Dietary forage:grain ratio did not affect plasma FFA.     

Symmetrical four-bar coupler curves,containing three cusps

Symmetrical coupler curves are easier to analyse than non-symmetrical ones. This is particular true if one diseres to find the double points or the cuspidal points of such curves. It appears that symmetrical coupler curves containing three cusps are governed by one parameter only, which happens to be the coupler-angle. The dimensions of the generating four-bar then meet very simple formulas, enabling the designer of these linkages to face other requirements as well; such as the requirement of a straight-stretch in the coupler curve.      

∇-Und 8-förmige Koppelkurven der Kurbelschwinge

Zusammenfassung Die vorliegende Abhandlung untersucht symmetrische ∇-f?rmige und 8-f?rmige Koppelkurven, die wenigstens zwei Wendepunkte enthalten. Dabei werden auch die Sonderf?lle berücksichtigt. Au?er Hinweisen auf konstruktive Ma?nahmen finden sich ausführliche Berechnungsanleitungen für die Gelenkvierecke, die solche Kurven erzeugen. Als besonders praktische erweist es sich, da? man in allen F?llen mit zwei voneinander unabh?ngigen Parametern auskommt, welche auch die natürlichen Vorgaben für eine solche Konstruktion sind. Es handelt sich hierbei zum einen um den Winkel 2τ, der von den beiden n?herungsweise geraden Bahnabschnitten eingeschlossen wird, zum anderen um α₀/π, den auf einen ganzen Zyklus bezogenen Kurbelwinkel zwischen den zwei symmetrisch zueinander, liegenden Wendepunktslagen. Die besten (d.h. die übertragungsgünstigsten) Gelenkvierecke mit ∇-und 8-f?rmigen Koppelkurven k?nnen aus Diagrammen entnommen werden. Zus?tzlich erleichtern Tabellen das Auffinden besonders guter Geradführungen. Mit diesen Hilfsmitteln ist es für den Konstrukteur einfach geworden, ein seinen Anforderungen genügendes Getriebe auszuw?hlen. Die vorgestellten Getriebe sind u.a. sehr gut zum Antrieb eines Malteserkreuzes geeignet. Weitere Anwendungen findet man in der Richtlinie VDI 2728. Herrn It.A.T.J.M. Smals, Dozent für Automatisierung der Fertigung an der Fakult?t des Maschinenwesens der Technische Universit?t Eindhoven, Niederlande, ist der Autor sehr verbunden für das von ihm weiterentwickelte Computerprogramm, dessen Ergebnisse in diesem Aufsatz benutzt worden sind. Herrn Dipl.-Math.P. Tolle, im Fachgebiet Maschinenelemente und Getriebetechnik der Universit?t der Bundeswehr Hamburg, Bundesrepublik Deutschland, dankt der Autor für die von ihm vorgeschlagenen Verbesserungen des Textes der vorliegenden Abhandlung. Schlie?lich dankt der Autor seiner Ehefrau,M. Dijksman-Margarit, für die sch?nen Ausarbeitungen der Zeichnungen.     

Structural characterization of U(VI) in apatite by X-ray absorption spectroscopy

X-ray absorption spectroscopy was used to determine the local structure of U(VI) within synthetic fluorapatite at a concentration of 2.3 wt %. Extended X-ray absorption fine structure indicates that U(VI) substitutes into the Ca1 site. To accommodate this substitution the apatite structure significantly distorts such that the Ca1 site approximates octahedral coordination, with six uniform U-0 distances of 2.06A. An X-ray adsorption edge structure, with two inflection points, and optical emission spectra are consistent with 6d orbital crystal field splitting. These results indicate that significant amounts of U(VI) can be accommodated in the apatite structure but with an unexpected coordination, which may bear on the ultimate development of apatite-hosted nuclear-waste forms.     

Effects of prophylactic vitamin administration of physical fitness of schoolchildren in the Arctic Regions]

The effectiveness of prophylactic vitamin administration to schoolchildren in the Arctic region was evaluated in the biochemical investigation of schoolchildren by the assay of vitamins C, A, E, B1, B2, B6, B12 and folic acid in their blood serum before and after "Undevitum" intake. Deficiency of a number of vitamins was detected. It was shown that regular consumption of multivitamin "Undevitum" produced a positive effect on the parameters of their physical activity, the highest effect was observed in children with the normotensive reaction to loading, and it was less expressed in those with pathological hemodynamic reactions to the loading.