bluuebunny/crossref_metadata_2025 huggingface dataset:
Essential oil composition of Prasium majus L. from Greece
Authors: Basta A. , Tzakou O. , Couladis M. , Yannitsaros A.
Published: May 2007

The essential oils from the aerial parts of Prasium majus (Labiatae), collected in two phenological stages in Greece, were analysed by GC–MS. Thirty‐two compounds were identified, representing 99.8–99.9% of the total oils. The major constituents in sample A were 1‐octen‐3‐ol (20.7%), α‐pinene (14.7%) and linalool (13.8%), while those of sample B were dehydro‐aromadendrene (31.8%), caryophyllene oxide (13.7%) and 1‐octen‐3‐ol (12.4%). Copyright © 2007 John Wiley & Sons, Ltd.
Composition of essential oil, concrete, absolute, wax and headspace volatiles of Murrarya paniculata (Linn.) Jack flowers
Authors: Rout P. K. , Rao Y. R. , Sree A. , Naik S. N.
Published: May 2007

Murraya paniculata (Linn) Jack, syn. M. exotica Linn., commonly known as orange jessamine, is grown in gardens for its large clusters of fragrant flowers. Distillation of the fresh flowers in water furnished the essential oil in 0.027% yield. Extraction of the fresh flowers with pentane afforded the concrete (0.78%). Precipitating the waxes from the concrete with methanol gave absolute (0.62%). The chemical composition of essential oil, concrete, absolute and wax were analysed by GC and GC–MS. The components of essential oil in significant amounts were δ‐elemene (1.4%), (E)‐caryophyllene (3.6%), germacrene D (2.7%), (E)‐nerolidol (25.7%), benzyl benzoate (8.1%), phenyl ethyl benzoate (8.0%) and manool (18.7%). The major components in the concrete and absolute, respectively, were phenyl ethyl alcohol (2.9%, 3.0%), indole (0.8%, 1.0%), (E)‐nerolidol (6.5%, 7.0%), benzyl benzoate (5.0%, 6.5%), phenyl ethyl benzoate (8.0%, 8.6%) and manool (25.2%, 27.9%). The methanol‐insoluble wax contained (E)‐nerolidol (2.6%), manool (9.4%) and most of the fatty acids/esters. The composition of the volatile components in the headspace emitted by flowers still on the branch (live flowers) and also by the picked flowers was determined by HS–SPME on a PDMS fibre and these results are also presented. The major components found in the headspace were linalool, indole, (E)‐caryophyllene, germacrene D, bicyclogermacrene and (E,E)‐α‐farnesene. Copyright © 2007 John Wiley & Sons, Ltd.
Determination of flavour profile in Iranian fragrant rice samples using cold‐fibre SPME–GC–TOF–MS
Authors: Ghiasvand Ali Reza , Setkova Lucie , Pawliszyn Janusz
Published: May 2007

A newly developed cold‐fibre solid‐phase microextraction (CF–SPME) device, as a powerful system for collection and concentration of volatile compounds, coupled to a gas chromatography time‐of‐flight mass spectrometer (GC–TOF–MS) system, equipped with a multi‐channel ion detector and a deconvolution software, was investigated for the analysis of volatile flavour compounds in the headspace of rice samples. The proposed combination provided a powerful system for easy and rapid screening of a wide range of flavours in fragrant rice samples. Based on four target analytes, including 2‐acetyl‐1‐pyrroline as a key odorant compound, different experimental parameters were optimized. The effect of the fibre composition, moisture present in the matrix, extraction temperature and time and desorption time were investigated. Nine Iranian and two Indian fragrant rice varieties were analysed using CF–SPME and the results were compared with commercial SPME fibres. The results revealed that uncooked rice samples can be successfully analysed even as dry kernels, without adding water, utilizing the fully automated CF–SPME–GC–TOF–MS. When using PDMS fibre, a clearly distinguishable peak was seen for 2‐acetyl‐1‐pyrroline by simultaneous cooling of the fibre and heating of rice matrices as dry whole grains. Copyright © 2007 John Wiley & Sons, Ltd.
Aroma volatile constituents of Colombian varieties of mango (Mangifera indica L.)
Authors: Quijano Clara E. , Salamanca Guillermo , Pino Jorge A.
Published: May 2007

The volatile components of nine Colombian mango varieties were investigated by means of simultaneous distillation–extraction, GC and GC–MS. One hundred and forty‐five compounds were identified, of which eight were found for the first time in mango fruit. The total concentration of volatiles was ca. 17–75 mg/kg fresh fruit. Terpene hydrocarbons were the major volatiles of all varieties, the dominant terpenes being δ‐3‐carene (Haden, Irwin, Manila and Tommy Atkins), α‐pinene (Hilacha and Vallenato), α‐phellandrene (Van Dyke) and terpinolene (Yulima), while no dominant terpene was found in the Springfield variety. Other qualitative and quantitative differences between the varieties were demonstrated. Copyright © 2007 John Wiley & Sons, Ltd.
Influence of temperature and pH on the kinetics of the Sharon nitritation process
Authors: Van Hulle Stijn WH , Volcke Eveline IP , Teruel Josefa López , Donckels Brecht , van Loosdrecht Mark CM , Vanrolleghem Peter A
Published: May 2007

The SHARON (Single reactor High activity Ammonia Removal Over Nitrite) process is an innovative process that improves the sustainability of wastewater treatment, especially when combined with an Anammox process. It aims at ammonium oxidation to nitrite only, while preventing further nitrate formation. In order to optimize this process by means of modelling and simulation, parameters of the biological processes have to be assessed. Batch tests with SHARON sludge clearly showed that ammonia rather than ammonium is the actual substrate and nitrous acid rather than nitrite is the actual inhibitor of the ammonium oxidation in the SHARON process. From these batch tests the ammonia affinity constant, the nitrous acid inhibition constant and the oxygen affinity constant were determined to be 0.75 mgNH3‐N L−1, 2.04 mgHNO2‐N L−1 and 0.94 mgO2 L−1. The influence of pH and temperature on the oxygen uptake rate of SHARON biomass was determined, indicating the existence of a pH interval between 6.5 and 8 and a temperature interval from 35 to 45 °C where the biomass activity is maximal. The kinetic parameters of the SHARON process were determined based on batch experiments. These parameters can now be implemented in a simulation model for further optimization of the SHARON process. Copyright © 2007 Society of Chemical Industry
Osteointegration of titanium and hydroxyapatite rough surfaces in healthy and compromised cortical and trabecular bone: in vivo comparative study on young, aged, and estrogen‐deficient sheep
Authors: Borsari Veronica , Fini Milena , Giavaresi Gianluca , Rimondini Lia , Consolo Ugo , Chiusoli Loris , Salito Armando , Volpert Andreas , Chiesa Roberto , Giardino Roberto
Published: May 2007

The osteointegration rate of titanium (Ti; TI01) and duplex Ti plus HA (HT01) coating systems with high surface roughness was investigated in healthy, aged, and oestrogen‐deficient sheep. After having evaluated the bone quality, TI01 and HT01 rods were implanted in the tibial diaphyses (two implants for each tibia) and epiphyses (1 implant for each tibia) of five young (YOUNG), five aged (AGED), and five aged and ovariectomized (OVX) sheep. The iliac crest trabecular bone volume (BV/TV) and number (Tb.N) in OVX sheep were respectively 33.5% and 28.5% lower than in YOUNG sheep (p < 0.005) and lower than in the AGED group (BV/TV, −17%; Tb.N, −13.5%; not significant); in the OVX group the trabecular separation was 77.9% higher than in YOUNG (p < 0.05) and 30.9% higher than in AGED animals. Lumbar vertebrae L5 bone mineral density was significantly lower in AGED (8.9%, p < 0.05) and OVX sheep (19.3%, p < 0.0005) when compared with YOUNG animals. Five samples of five sheep from each group were analyzed for each observation. At 3 months, in cortical bone both affinity index and pushout test results showed no significant differences between the two materials in each group of animals. In trabecular bone, the affinity index of HT01 was significantly higher than that of TI01 in each group of animals (YOUNG, 90.7%; AGED, 76.9%; OVX, 49.9%) with no significant differences between groups. In conclusion, the performance of TI01 and HT01 surfaces was high not only in YOUNG, but also in OVX animals and, therefore, they might be useful for aged and osteoporotic patients. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 25:1250–1260, 2007
Characterization of sulphate transporters in isolated bovine articular chondrocytes
Authors: Meredith David , Gehl Katharina A. , Seymour John , Ellory J. Clive , Wilkins Robert J.
Published: May 2007

Uptake of SO by articular chondrocytes is an essential step in the pathway for sulphation of glycosaminoglycans (GAGs), with mutations in SO transport proteins resulting in abnormalities of skeletal growth. In the present study, the transporters mediating SO transport in bovine articular chondrocytes have been characterized. Expression of candidate transporters was determined using RT‐PCR, while SO transport was measured in radioisotope flux experiments. RT‐PCR experiments showed that bovine articular chondrocytes express three transporters known to transport SO: AE2 (SLC4a2), DTDST (SLC26a2), and SLC26a11. Other transporters—NaS‐1 (SLC13a1), SAT‐1 (SLC26a1), DRA (SLC26a3), SLC26a6 (PAT1), SLC26a7, SLC26a8 (Tat‐1), and SLC26a9—were, however, not detected. In functional experiments, SO uptake was temperature‐sensitive, inhibited by 60% by DIDS (50 µM) and exhibited saturation kinetics, with a Km value of 16 mM. Uptake was also inhibited at alkaline extracellular pH. In further experiments, a Ki value for DIDS inhibition of SO efflux of 5 µM was recorded. A DIDS‐sensitive component of SO efflux persisted in solutions lacking Cl− ions. These data are interpreted as evidence for the preferential operation of carrier‐mediated exchange of SO for Cl−, while an alternative SO–OH− exchange mode is also possible. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res
Definitizability of Certain Functions and the Existence of Eigenvectors of Unitary Operators in Pontrjagin Spaces
Authors: Sasvári Zoltán
Published: May 2007

LetPkc(G) denote the set of continuous functions withknegative squares on a locally compact commutative groupG.Every functionfϵPkc(G) is definitizable in the sense thatmagnified imageis positive definite for certain complex measures ω onGwith finite support [9]. The proof of this fact was base on a result of M. A. Naimark about common nonpositive eigenvectors of commuting unitary operators in a Pontrjagin space. It is the aim of this note to prove without any use of the theory of Pontrjagin spaces the definitizability of functionsfϵPkc(G) which are of polynomial growth. In Section 3 we show, how the definitizability of functionsfϵPkc(G) can be used to prove the existence of common non‐positive eigenvectors of commuting unitary operators in a Pontrjagin space.
On the Almost Sure Convergence of Floating‐Point Mantissas and Benford's Law
Authors: Schatte Peter
Published: May 2007

Let Y1, Y2,… be a sequence of random variables and let Mn be the floating‐point mantissa of Yn. Further let 11,x)(·) denote the indicator of the interval (1,x). If Yn/n→Z a.s., where Z ≠ 0 is a further random variable, then the sequence 1(1,x)(Mn) converges a.s. to log x in the sense of 𝒳 ∞‐means and logarithmic means, respectively. The speed of convergence in this relations is estimated. As a conclusion, a further argument for Benford's law is provided.
Critical behavior of some measure‐valued processes
Authors: Fleischmann Klaus
Published: May 2007

The so‐called weighted occupation time process Y associated with some critical measur‐evalued branching process is considered. Y has absolutely continuous states provided that the dimension of the phase space is small enough. The corresponding density functions form a random process η. In some cases there exists a critical dimension such that η. considered in the space‐time diagram, is a self‐similar random non‐negative field. This self‐similar field is infinitely divisible but not stable.
Symmetries on Riemannian Manifolds
Authors: Ledger A. J. , Vanhecke L.
Published: May 2007

Locally symmetric KÄHLER manifolds may be characterized as almost HERMITian manifolds with symplectic or holomorphic local geodesic symmetries. We extend the notion of a local geodesic symmetry and in particular, give a similar characterization of all RIEMANNian locally s‐regular manifolds with an s‐structure of odd order.
Asymptotic Behaviour of an Empirical Nearest‐Neighbour Distance Function for Stationary Poisson Cluster Processes
Authors: Heinrich Lothar
Published: May 2007

Summary. For stationary POISSONcluster processes (PCP's) Ø onRthe limit behaviour, asv(D)→ ∞, of the quantity\documentclass{article}\pagestyle{empty}\begin{document}$ \left({v\left(D \right)} \right)^{ - 1} \sum\limits_{x\varepsilon D:\phi \left({\left\{ x \right\}} \right) = 1} {\chi \left({x,r} \right)} $\end{document}, where χ(x, r) = 1, if Ø(b(x, r)) = 1, and χ(x, r) = 0 otherwise, is studied. A central limit theorem for fixedr> 0 and the weak convergence of the normalized and centred empirical process on [0,R] to a continuous GAUSSian process are proved. Lower and upper bounds for the nearest neighbour distance functionP1({φ:Y(b(0,r))≧1}) of a stationary PCP are given. Moreover, a representation of higher order Palm distributions of PCP's and a central limit theorem form‐dependent random fields with unboundedmare obtained. Both these auxiliary results seems to be of own interest.
Spectral Radius and Degree Sequence
Authors: Hofmeister M.
Published: May 2007

For a nonregular graph there is exactly one value of p such that the p‐mean of its degree sequence is equal to the spectral radius. We try to investigate the structural content of this so‐called spectral mean characteristic; in particular, we characterize the connected graphs of spectral mean characteristic 2.
Gender‐related and age‐related urinalysis of healthy subjects by NMR‐based metabonomics
Authors: Psihogios Nikolaos G. , Gazi Irene F. , Elisaf Moses S. , Seferiadis Konstantin I. , Bairaktari Eleni T.
Published: May 2007

NMR‐based metabonomic analysis is a well‐established approach to characterizing healthy and diseased states. The aim of this study was to investigate inter‐individual variability in the metabolic urinary profile of a healthy Greek population, not subjected to strict dietary limitations, by NMR‐based metabonomics. The overall metabonomic urinalysis showed a homogeneous distribution among the population. The metabolic profile was examined in relation to gender and age, and reference intervals of major metabolites were determined. Multivariate data analysis led to the construction of two robust models that were able to predict the class membership of the subjects studied according to their gender and age. The most influential low molecular weight metabolites responsible for the differences in gender groups were citrate, creatinine, trimethylamine N‐oxide, glycine, creatine and taurine, and for the differences in age groups they were citrate, creatinine, trimethylamine N‐oxide and an unidentified metabolite (δ 3.78). Copyright © 2007 John Wiley & Sons, Ltd.
Identification of antioxidant phenolic compounds in feverfew (Tanacetum parthenium) by HPLC‐ESI‐MS/MS and NMR
Authors: Wu Changqing , Chen Feng , Wang Xi , Wu Yonnie , Dong Meidui , He Guoqing , Galyean Ronald D. , He Lilin , Huang Guohui
Published: May 2007

Antioxidant polyphenolic acids in the medicinal herb feverfew (Tanacetum parthenium) were isolated through in vitro bioassay‐orientated antioxidant tests in response to 1,1‐diphenyl‐2‐picrylhydrazyl (DPPH•) free radical scavenging and Fe2+‐chelating activities. Purification of the active compounds and their structural elucidation involved a variety of techniques including open‐column chromatography, HPLC, GC‐MS, LC‐MS and NMR. Major compounds with potent DPPH• scavenging activities were characterised as 3,5‐, 4,5‐ and 3,4‐di‐O‐caffeoylquinic acids (DCQAs). This is the first report of DCQAs found in feverfew. Copyright © 2007 John Wiley & Sons, Ltd.
Determination of pseudojujubogenin glycosides from Brahmi based on immunoassay using a monoclonal antibody against bacopaside I
Authors: Phrompittayarat Watoo , Putalun Waraporn , Tanaka Hiroyuki , Jetiyanon Kanchalee , Wittaya‐Areekul Sakchai , Ingkaninan Kornkanok
Published: May 2007

Bacopa monnieri (L.) Wettst. (Brahmi) is an Ayurvedic medicinal plant used for centuries as a memory enhancer. Dammarane‐type triterpenoid saponins classified as pseudojujubogenin and jujubogenin glycosides are reported as the active components in this plant. In this study, the monoclonal antibody (MAb) against bacopaside I, a major pseudojujubogenin glycoside found in Brahmi, was produced and characterised. Bacopaside I was conjugated with bovine albumin serum to prepare an immunogen. Hybridomas secreting a monoclonal antibody against bacopaside I was produced by fusing splenocytes from an immunised mouse and SP2/0‐Ag14 myeloma cells. The results showed that the antibodies were raised specifically against pseudojujubonin glycosides. An enzyme‐linked immunosorbant assay (ELISA) using anti‐bacopaside I MAb was performed in the range of 1.95–62.5 ng/mL of bacopaside I, with a limit of detection of 0.5 ng/mL. The method was validated and the practical use of the ELISA for analysing saponin glycosides from Brahmi was demonstrated. Copyright © 2007 John Wiley & Sons, Ltd.
Moleküle in “Slow Motion”: Abbremsen und Speichern kalter Moleküle
Authors: van de Meerakker Bas , Meijer Gerard
Published: May 2007

Langsame und damit sehr kalte Moleküle bieten eine ähnlich aufregende Perspektive wie ultrakalte Atome. Doch ihre Herstellung ist schwieriger, denn meist versagt die bei Atomen erfolgreiche Laserkühlung. Eine Möglichkeit bietet der Stark‐Verzögerer. Er arbeitet wie ein inverser Linearbeschleuniger und bremst über den Stark‐Effekt sogar elektrisch neutrale Moleküle ab. Diese langsamen Moleküle kann dann ein Speicherring aufnehmen oder eine elektrostatische Quadrupol‐Falle fast zum Stillstand bringen. Kollisionsexperimente zwischen langsamen OH‐Molekülen und Xe‐Atomen haben jüngst erste interessante Einblicke in diese Streuprozesse geliefert. Bei ihnen kann die Energie gerade noch ausreichen, um die quantisierten Rotationszustände der beteiligten Moleküle zu ändern.
Spiel, Satz und Sieg: Physik und Mathematik des Tennisspiels
Authors: Thaller Sigrid , Mathelitsch Leopold
Published: May 2007

Die Energieübertragung zwischen Schläger und Ball hängt von den Schwingungseigenschaften beider ab, wichtig ist zudem der Auftreffpunkt des Balles auf der Schlägerfläche. Die Rotation des Balles in der Luft ermöglicht unterschiedliche Flugbahnen. Selbststabilisierende Schlagbewegungen können kleine Ungenauigkeiten des Spielers ausgleichen. Der Zufall beeinflusst die Gewinnchancen weniger als im Fußball. Die Phase der Spielerbewegungen relativ zueinander gibt Auskunft über den Spielverlauf.
Laser kühlen mechanische Oszillatoren
Authors: Kippenberg Tobias
Published: May 2007

Kürzlich ist es drei Forschungsgruppen erstmalig gelungen, mechanische Oszillatoren mit Hilfe von Laserlicht zu kühlen. Damit konnten sie die mehr als drei Jahrzehnte alten Vorhersagen des russischen Theoretikers Vladimir Braginsky bestätigen. Die neuartige Methode könnte es in Zukunft erlauben, mikroskopische Objekte in den quantenmechanischen Grundzustand zu kühlen.
Wenn Funken Wellen schlagen: Zum 150. Geburtstag von Heinrich Hertz
Authors: Wegener Martin
Published: May 2007

Mit seinen Karlsruher Experimenten zu elektromagnetischen Wellen hat Heinrich Hertz 1887 die Maxwellsche Theorie der Elektrodynamik bestätigt und zugleich den Grundstein für die heutige Informationsgesellschaft gelegt. Mit seinen Experimenten zum Photoeffekt aus dem gleichen Jahr hat er – ohne dass ihm dies klar sein konnte – auch die Grenzen der Maxwellschen Theorie aufgezeigt und eine Tür zum Photon sowie zur Photonik geöffnet. Und dabei hat das “Jahrhundert des Photons”, wie manche das 21. Jahrhundert nennen, mit Heinrich Hertz‘ 150. Geburtstag gerade erst begonnen.
Rinderpapier und andere Cellulosefolien
Authors: Vilgis Thomas
Published: May 2007

Bei klassischen Spionagefilmen, zu Zeiten als geheime Nachrichten noch über Papier vermittelt wurden, konnte immer wieder gelacht werden, sobald der gejagte Agent den Zettel rasch in den Mund schob, mühsam kaute und schluckte. Empfindliche Zuschauer beschlich ein ungutes Gefühl im Hals. Heutzutage spielt leichtes, knuspriges Esspapier eine gewichtige Rolle in der Molekularküche und führt uns in die physikalische Welt der Cellulosen.
Quantitative proteomic comparison of mouse peroxisomes from liver and kidney
Authors: Mi Jia , Kirchner Eva , Cristobal Susana
Published: May 2007

The peroxisome plays a central role in the catabolic and anabolic pathways that contribute to the lipid homeostasis. Besides this main function, this organelle has gained functional diversity. Although several approaches have been used for peroxisomal proteome analysis, a quantitative protein expression analysis of peroxisomes from different tissues has not been elucidated yet. Here, we applied a 2‐DE‐based method on mouse liver and kidney peroxisomal enriched fractions to study the tissue‐dependent protein expression. Ninety‐one spots were identified from the 2‐DE maps from pH 3.0–10.0 and 51 spots from the basic range corresponding to 31 peroxisomal proteins, 10 putative peroxisomal, 6 cytosolic, 17 mitochondrial and 1 protein from endoplasmic reticulum. Based on the identification and on the equivalent quality of both tissue preparations, the differences emerging from the comparison could be quantified. In liver, proteins involved in pathways such as α‐ and β‐oxidation, isoprenoid biosynthesis, amino acid metabolism and purine and pirimidine metabolism were more abundant whereas in kidney, proteins from the straight‐chain fatty acid β‐oxidation were highly expressed. These results indicate that tissue‐specific functional classes of peroxisomal proteins could be relevant to study peroxisomal cellular responses or pathologies. Finally, a web‐based peroxisomal proteomic database was built.
Antibody microarray‐based profiling of complex specimens: systematic evaluation of labeling strategies
Authors: Kusnezow Wlad , Banzon Virryan , Schröder Christoph , Schaal René , Hoheisel Jörg D. , Rüffer Sven , Luft Petra , Duschl Albert , Syagailo Yana V.
Published: May 2007

Antibody microarrays have often had limited success in detection of low abundant proteins in complex specimens. Signal amplification systems improve this situation, but still are quite laborious and expensive. However, the issue of sensitivity is more likely a matter of kinetically appropriate microarray design as demonstrated previously. Hence, we re‐examined in this study the suitability of simple and inexpensive detection approaches for highly sensitive antibody microarray analysis. N‐hydroxysuccinimidyl ester (NHS)‐ and Universal Linkage System (ULS)‐based fluorescein and biotin labels used as tags for subsequent detection with anti‐fluorescein and extravidin, respectively, as well as fluorescent dyes were applied for analysis of blood plasma. Parameters modifying strongly the performance of microarray detection such as labeling conditions, incubation time, concentrations of anti‐fluorescein and extravidin and extent of protein labeling were analyzed and optimized in this study. Indirect detection strategies whether based on NHS‐ or ULS‐chemistries strongly outperformed direct fluorescent labeling and enabled detection of low abundant cytokines with many dozen‐fold signal‐to‐noise ratios. Finally, particularly sensitive detection chemistry was applied to monitoring cytokine production of stimulated peripheral T cells. Microarray data were in accord with quantitative cytokine levels measured by ELISA and Luminex, demonstrating comparable reliability and femtomolar range sensitivity of the established microarray approach.
A proteomic approach to studying the differentiation of neural stem cells
Authors: Skalnikova Helena , Halada Petr , Vodicka Petr , Motlik Jan , Rehulka Pavel , Hørning Ole , Chmelik Josef , Nørregaard Jensen Ole , Kovarova Hana
Published: May 2007

The mechanisms that regulate the maintenance of stem cell self‐renewal versus differentiation are complex and remain mostly unknown. Understanding neurogenesis and neural cell differentiation presents a unique challenge for the treatment of nervous system disorders. To gain more insight into molecular mechanisms of the differentiation of neural cells, we combined the advantage of porcine fetal neural stem cells (NSCs) in vitro differentiation model and proteomic analysis. Using 2‐DE followed by MS, we profiled constituent proteins of NSCs and their differentiated progenies at first and then indicated protein species that were significantly up‐ or down‐regulated during the differentiation. The largest identified group of constituent proteins was related to RNA and protein metabolism and processing, including chaperones, and the second largest consisted of proteins involved in cell organization (cytoskeleton and annexins). Differentiation of neural cells was found to be accompanied by changes in the expression of proteins involved in DNA and RNA binding, mRNA processing and transport, stress responses, iron storage, and redox regulation. Additional immunoblot analysis verified the induction of α‐B crystallin and heterogenous nuclear ribonucleoproteins (hnRNPs) A1 and A2/B1. Furthermore, immunocytochemistry demonstrated specific localization of α‐B crystallin in the cytoplasm or nucleus of glial cells and confirmed cellular expression patterns of hnRNPs A1 and A2/B1. These findings represent a significant step towards understanding neural cell differentiation and identification of the regulatory proteins associated with this process.
Evaluation of the substrate envelope hypothesis for inhibitors of HIV‐1 protease
Authors: Chellappan Sripriya , Kairys Visvaldas , Fernandes Miguel X. , Schiffer Celia , Gilson Michael K.
Published: May 2007

Crystallographic data show that various substrates of HIV protease occupy a remarkably uniform region within the binding site; this region has been termed the substrate envelope. It has been suggested that an inhibitor that fits within the substrate envelope should tend to evade viral resistance because a protease mutation that reduces the affinity of the inhibitor will also tend to reduce the affinity of substrate, and will hence decrease the activity of the enzyme. Accordingly, inhibitors that fit the substrate envelope better should be less susceptible to clinically observed resistant mutations, since these must also allow substrates to bind. The present study describes a quantitative measure of the volume of a bound inhibitor falling outside the substrate envelope, and observes that this quantity correlates with the inhibitor's losses in affinity to clinically relevant mutants. This measure may thus be useful as a penalty function in the design of robust HIV protease inhibitors. Proteins 2007. © 2007 Wiley‐Liss, Inc.
A brief review of Phase 1 and Clinical Pharmacology statistics in clinical drug development
Authors: Patterson Scott D. , Jones Byron
Published: May 2007

Following a brief description of historical Phase 1 research, Clinical Pharmacology studies, and the role of statistics in this setting, Phase 1 study design and statistical analysis are reviewed. A description of design and analysis for Clinical Pharmacology studies is also provided, and the role of statistics in this area of drug development in the future is discussed. While challenging, this area of statistics in drug development is likely to have an active and engaging future. Copyright © 2007 John Wiley & Sons, Ltd.
Stabilization of single‐input nonlinear systems using higher‐order term compensating sliding mode control
Authors: Voytsekhovsky Dmitry , Hirschorn Ronald M.
Published: May 2007

In this work we investigate a new approach for stabilizing nonlinear systems using sliding mode control. The idea behind this method is the following: given an approximately feedback linearizable system, we define a local coordinate transformation and then find a sliding mode controller, in the new coordinates, which steers the state to the origin. Our results are compared to those obtained using approximate feedback linearization‐based sliding mode control. Copyright © 2007 John Wiley & Sons, Ltd.
Model selection for multi‐component frailty models
Authors: Ha Il Do , Lee Youngjo , MacKenzie Gilbert
Published: May 2007

Various frailty models have been developed and are now widely used for analysing multivariate survival data. It is therefore important to develop an information criterion for model selection. However, in frailty models there are several alternative ways of forming a criterion and the particular criterion chosen may not be uniformly best. In this paper, we study an Akaike information criterion (AIC) on selecting a frailty structure from a set of (possibly) non‐nested frailty models. We propose two new AIC criteria, based on a conditional likelihood and an extended restricted likelihood (ERL) given by Lee and Nelder (J. R. Statist. Soc. B1996;58:619–678). We compare their performance using well‐known practical examples and demonstrate that the two criteria may yield rather different results. A simulation study shows that the AIC based on the ERL is recommended, when attention is focussed on selecting the frailty structure rather than the fixed effects. Copyright © 2007 John Wiley & Sons, Ltd.
Performance of the trim and fill method in the presence of publication bias and between‐study heterogeneity
Authors: Peters Jaime L. , Sutton Alex J. , Jones David R. , Abrams Keith R. , Rushton Lesley
Published: May 2007

The trim and fill method allows estimation of an adjusted meta‐analysis estimate in the presence of publication bias. To date, the performance of the trim and fill method has had little assessment. In this paper, we provide a more comprehensive examination of different versions of the trim and fill method in a number of simulated meta‐analysis scenarios, comparing results with those from usual unadjusted meta‐analysis models and two simple alternatives, namely use of the estimate from: (i) the largest; or (ii) the most precise study in the meta‐analysis. Findings suggest a great deal of variability in the performance of the different approaches. When there is large between‐study heterogeneity the trim and fill method can underestimate the true positive effect when there is no
publication bias. However, when publication bias is present the trim and fill method can give estimates that are less biased than the usual meta‐analysis models. Although results suggest that the use of the estimate from the largest or most precise study seems a reasonable approach in the presence of publication bias, when between‐study heterogeneity exists our simulations show that these estimates are quite biased. We conclude that in the presence of publication bias use of the trim and fill method can help to reduce the bias in pooled estimates, even though the performance of this method is not ideal. However, because we do not know whether funnel plot asymmetry is truly caused by publication bias, and because there is great variability in the performance of different trim and fill estimators and models in various meta‐analysis scenarios, we recommend use of the trim and fill method as a form of sensitivity analysis as intended by the authors of the method. Copyright © 2007 John Wiley & Sons, Ltd.
Constructing multiple test procedures for partially ordered hypothesis sets
Authors: Edwards David , Madsen Jesper
Published: May 2007

A popular method to control multiplicity in confirmatory clinical trials is to use a so‐called hierarchical, or fixed sequence, test procedure. This requires that the null hypotheses are ordered a priori, for example, in order of clinical importance. The procedure tests the hypotheses in this order using α‐level tests until one is not rejected. It then stops, so that no subsequent hypotheses are eligible for rejection. This procedure strongly controls the familywise error rate (FWE), that is to say, the probability that any true hypotheses are rejected.

This paper describes a simple generalization of this approach in which the null hypotheses are partially ordered. It is convenient to display the partial ordering in a directed acyclic graph (DAG). We consider sequentially rejective procedures based on the partial ordering, in which a hypothesis is tested only when all preceding hypotheses have been tested and rejected. In general such procedures do not control the FWE, but it is shown that when certain intersection hypotheses are added, strong control of the FWE is obtained. The purpose of the method is to construct inference strategies for confirmatory clinical trials that better reflect the trial objectives. Copyright © 2007 John Wiley &
Sons, Ltd.
Inferences on the mean response in a log‐regression model: The generalized variable approach
Authors: Tian Lili , Wu Jianrong
Published: May 2007

This paper proposes a novel approach for the confidence interval estimation and hypothesis testing of the mean response in a log‐regression model using the concept of generalized variable. Simulation studies demonstrate that the proposed confidence intervals have satisfying coverage probabilities. The proposed approach can be simply carried out by a few simulation steps. Therefore, it is an ideal candidate for making inferences about the mean response in a log‐regression model. Copyright © 2007 John Wiley & Sons, Ltd.
Analysis, synthesis, systems thinking and the scientific method: rediscovering the importance of open systems
Authors: Barton John , Haslett Tim
Published: May 2007

This paper reconsiders the role of systems thinking in science and addresses an issue raised by Peter Checkland some 25 years ago, that of the relationship between systems thinking, analysis and the scientific method. The paper argues that the scientific method is most usefully interpreted as a dialectic between analysis and synthesis supported by the triadic logic of C.S. Peirce, and that the role of systems thinking is to frame this dialectic. Three generic forms of the system concept are identified—closed systems, input‐output systems and open systems. Consequently, systems thinking is shown to play a central role in mainstream science. The paper concludes that a system is best defined as a cognitive construct for making sense of complexity and the organization of knowledge and that contemporary system thinking is best identified as the ethical, scientific pursuit of knowledge using the socio‐ecological (open) systems frame. Copyright © 2007 John Wiley & Sons, Ltd.
Verification of clock synchronization algorithms: experiments on a combination of deductive tools
Authors: Barsotti Damián , Nieto Leonor Prensa , Tiu Alwen
Published: May 2007

We report on an experiment in combining the theorem prover Isabelle with automatic first-order arithmetic provers to increase automation on the verification of distributed protocols. As a case study for the experiment we verify several averaging clock synchronization algorithms. We present a formalization of Schneider’s generalized clock synchronization protocol [Sch87] in Isabelle/HOL. Then, we verify that the convergence functions used in two clock synchronization algorithms, namely, the Interactive Convergence Algorithm (ICA) of Lamport and Melliar-Smith [LMS85] and the Fault-tolerant Midpoint algorithm of Lundelius–Lynch [LL84], satisfy Schneider’s general conditions for correctness. The proofs are completely formalized in Isabelle/HOL. We identify parts of the proofs which are not fully automatically proven by Isabelle built-in tactics and show that these proofs can be handled by automatic first-order provers with support for arithmetics.
Estimates of biomass and primary productivity in a high‐altitude maple forest of the west central Himalayas
Authors: Garkoti S. C.
Published: May 2007

The paper describes the biomass and productivity of maple (Acer cappadocicum) forest occurring at an altitude of 2,750 m in the west central Himalayas. Total vegetation biomass was 308.3 t ha−1, of which the tree layer contributed the most, followed by herbs and shrubs. The seasonal forest‐floor litter mass varied between 5.4 t ha−1(in rainy season) and 6.6 t ha−1(in winter season). The annual litter fall was 6.2 t ha−1, of which leaf litter contributed the largest part (59% of the total litter fall). Net primary productivity of total vegetation was 19.5 t ha−1year−1. The production efficiency of leaves (net primary productivity/leaf mass) was markedly higher (2.9 g g−1foliage mass year−1) than those of the low‐altitude forests of the region.
Prevacuolar compartment morphology in vps mutants of Saccharomyces cerevisiae
Authors: Hedman Jamie M. , Eggleston Matthew D. , Attryde Amanda L. , Marshall Pamela A.
Published: May 2007

Over 60 genes have been identified that affect protein sorting to the lysosome‐like vacuole in Saccharomyces cerevisiae. Cells with mutations in these vacuolar protein sorting (vps) genes fall into seven general classes based upon their vacuolar morpholology. Class A mutants have a morphologically wild type vacuole, while Class B mutants have a fragmented vacuole. There is no discernable vacuolar structure in Class C mutants. Class D mutants have a slightly enlarged vacuole, but Class E mutants have a normal looking vacuole with an enlarged prevacuolar compartment (PVC), which is analogous to the mammalian late endosome. Class F mutants have a wild type appearing vacuole as well as fragmented vacuolar structures. vps mutants have also been found with a tubulo‐vesicular vacuole structure. vps mutant morphology is pertinent, as mutants of the same class may work together and/or have a block in the same general step in the vacuolar protein sorting pathway. We probed PVC morphology and location microscopically in live cells of several null vps mutants using a GFP fusion protein of Nhx1p, an Na+/H+ exchanger normally localized to the PVC. We show that cell strains deleted for VPS proteins that have been previously shown to work together, regardless of VPS Class, have the same PVC morphology. Cell strains lacking VPS genes that have not been implicated in the same pathway show different PVC morphologies, even if the mutant strains are in the same VPS Class. These new studies indicate that PVC morphology is another tier of classification that may more accurately identify proteins that function together in vacuolar protein sorting than the original vps mutation classes.
The Objective Burden in Partners of Heart Failure Patients; Development and Initial Validation of the Dutch Objective Burden Inventory
Authors: Luttik Marie Louise , Jaarsma Tiny , Tijssen Jan G.P. , van Veldhuisen Dirk J. , Sanderman Robbert
Published: May 2007

Background: Measures on objective caregiver burden in partners of Heart Failure patients are hardly available and never include HF specific aspects.

Aim: The main objective of our study was to develop an inventory that assesses the objective caregiver burden of partners of HF patients, including the full range of potential care giving demands.

Methods: To develop the inventory, six domains of caregiving demands were identified. Items for the domains were generated from the literature, expert opinion and existing scales. The original 50-items self-report inventory was administered to 321 partners of HF patients. Demographic data of HF partners were collected by questionnaire. Clinical data of the HF patients were collected by chart review.

Results: Component analysis led to exclusion of 12 original items and to a meaningful four-factor solution with a total explained variance of 43%. The components reflected four different kinds of care giving tasks; personal care, emotional, motivational and practical (treatment related) support. They demonstrated good internal consistency and initial validity was supported by a pattern of meaningful associations with external variables.

Conclusion: The Objective Burden Inventory is a promising inventory to assess objective care giving tasks performed by HF partners, including emotional and motivational support. It provides information on the caregiver situation that may help to develop effective interventions.
Exercise training reduces sympathetic nerve activity in heart failure patients treated with carvedilol
Authors: Fraga Raffael , Franco Fábio G. , Roveda Fabiana , de Matos Luciana N.J. , Braga Ana M.F.W. , Rondon Maria U.P.B. , Rotta Daniel R. , Brum Patricia C. , Barretto Antonio C.P. , Middlekauff Holly R. , Negrão Carlos E.
Published: May 2007

Background:

Evidence suggests that carvedilol decreases muscle sympathetic nerve activity (MSNA) in patients with heart failure (HF) but carvedilol fails to improve forearm vascular resistance and overall functional capacity. Exercise training in HF reduces MSNA and improves forearm vascular resistance and functional capacity.

Aims:

To investigate whether the beneficial effects exercise training on MSNA are maintained in the presence of carvedilol.

Methods and results:

Twenty seven HF patients, NYHA Class II–III, EF <35%, peak VO2 <20 ml/kg/min, treated with carvedilol were randomly divided into two groups: exercise training (n=15) and untrained (n=12). MSNA was recorded by microneurography. Forearm blood flow (FBF) was measured by venous occlusion plethysmography. The four‐month training program consisted of three 60‐min exercise/week on a cycloergometer. Baseline parameters were similar between groups. Exercise training reduced MSNA (–14±3.3 bursts/100 HB, p=0.001) and increased forearm blood flow (0.6±0.1 mL/min/100 g.p p>0.001) in HF patients on carvedilol. In addition, exercise training improved peak VO2 in HF patients (20±6%, p=0.002). MSNA, FBF and peak VO2 were unchanged in untrained HF patients on carvedilol.

Conclusion:

Exercise training reduces MSNA in heart failure patients treated with carvedilol. In addition, the beneficial effects of exercise training on muscle blood flow and functional capacity are still realized in patients on carvedilol.
Spongiform neurodegenerative disease in a Persian kitten
Authors: Salvadori Claudia , Lossi Laura , Arispici Mario , Cantile Carlo
Published: May 2007

A congenital encephalopathy with spongiform degeneration and prominent neuronal apoptosis was observed in a 4-month-old Persian male cat with a history of depressed mental status and ataxia. On clinical examination, signs included right head tilt, ventroflexion of the head and neck, and tetraparesis. Histological examination of the central nervous system revealed multifocal, bilateral and symmetrical vacuolar degeneration of the neuropil, mainly involving the cerebellar and vestibular nuclei area, the caudal colliculi, the mesencephalic nuclei, the tegmental area and the deeper layer of the cerebral cortex. Accumulation of phosphorylated neurofilaments was detected in neuronal perikarya of the deep cortical layers, hippocampus and thalamus. Numerous pyknotic and apoptotic neurons were also observed in the cerebral cortex. These neuropathological changes differ from those observed in previous reports of spongiform degeneration of the grey matter in cats and were suggestive of a congenital neurodegenerative disease.
Constant differences: Friedrich Wilhelm Bessel, the concept of the observer in early nineteenth-century practical astronomy and the history of the personal equation
Authors: HOFFMANN CHRISTOPH
Published: May 2007

In 1823 the astronomer Friedrich Wilhelm Bessel gave notice of an observational error which is now known as the personal equation. Bessel, however, never used this phrase to characterize the finding that when noting the time of a certain event observers show a considerable ‘involuntary constant difference’. From this starting point the paper develops two arguments. First, these involuntary differences subverted the concept of the ‘observing observer’. What had previously been defined as a reference point of trust and precision turned into a source of an error that resisted any wilful intervention. Second, and contrary to later suggestions, Bessel's findings did not initially lead to discussions and measures of permanent control. In everyday astronomical work the influence of such differences could be avoided by comparatively simple means. Taking this into account offers a new perspective both on the history of the personal equation and on the significance of Bessel's findings. Whereas the former has to be read as the history of a rather particular reaction to the phenomenon of constant differences, the latter is connected with a rather fundamental transition in the epistemology of the observer.
Stability properties of forced wakes
Authors: THIRIA B. , WESFREID J. E.
Published: May 2007

Thiria, Goujon-Durand & Wesfreid (J. Fluid Mech. vol. 560, 2006, p. 123), it was shown that vortex shedding from a rotationally oscillating cylinder at moderate Reynolds number can be characterized by the spatial coexistence of two distinct patterns, one of which is related to the forcing frequency in the near wake and the other to a frequency close to the natural one for the unforced case downstream of this locked region. The existence and the modification of these wake characteristics were found to be strongly affected by the frequency and the amplitude of the cylinder oscillation. In this paper, a linear stability analysis of these forced regimes is performed, and shows that the stability characteristics of such flows are governed by a strong mean flow correction which is a function of the oscillation parameters. We also present experiments on the spatial properties of the global mode and on the selection of the vortex shedding frequency as a function of the forcing conditions for Re = 150. Finally, we elucidate a diagram of locked and non-locked states, for a large range of frequencies and amplitudes of the oscillation.
Feedback control of subsonic cavity flows using reduced-order models
Authors: SAMIMY M. , DEBIASI M. , CARABALLO E. , SERRANI A. , YUAN X. , LITTLE J. , MYATT J. H.
Published: May 2007

Development, experimental implementation, and the results of reduced-order model based feedback control of subsonic shallow cavity flows are presented and discussed. Particle image velocimetry (PIV) data and the proper orthogonal decomposition (POD) technique are used to extract the most energetic flow features or POD eigenmodes. The Galerkin projection of the Navier–Stokes equations onto these modes is used to derive a set of nonlinear ordinary differential equations, which govern the time evolution of the eigenmodes, for the controller design. Stochastic estimation is used to correlate surface pressure data with flow-field data and dynamic surface pressure measurements are used to estimate the state of the flow. Five sets of PIV snapshots of a Mach 0.3 cavity flow with a Reynolds number of 105 based on the cavity depth are used to derive five different reduced-order models for the controller design. One model uses only the snapshots from the baseline (unforced) flow while the other four models each use snapshots from the baseline flow combined with snapshots from an open-loop sinusoidal forcing case. Linear-quadratic optimal controllers based on these models are designed to reduce cavity flow resonance and are evaluated experimentally. The results obtained with feedback control show a significant attenuation of the resonant tone and a redistribution of the energy into other modes with smaller energy levels in both the flow and surface pressure spectra. This constitutes a significant improvement in comparison with the results obtained using open-loop forcing. These results affirm that reduced-order model based feedback control represents a formidable alternative to open-loop strategies in cavity flow control problems even in its current state of infancy.