bluuebunny/crossref_metadata_2025 huggingface dataset:
A new rule for MESFET gate charge division based on the energy conservation principle
Authors: Kallio Antti I. , Valtonen Martti E.
Published: May 2004

The energy conservation problem in the MESFET gate charge model is presented. The energy conservation requirement leads to symmetrical transcapacitances in contradiction to the commonly accepted approaches. The transcapacitance symmetry is completely independent of device symmetry. The resulting small‐signal capacitances are reciprocal. Reciprocal capacitances are often considered charge non‐conservative because they do not contain transcapacitances, but in this approach reciprocity is the result of transcapacitance symmetry and the charge conservation problem is avoided since the charge‐based model includes the transcapacitances. A method for dividing the MESFET gate charge into gate‐drain and gate‐source portions based on the energy conservation rule is developed, and the method is applied to the well‐known Statz gate charge as an example. Copyright © 2004 John Wiley & Sons, Ltd.
CD8+ T cells regulate immune responses in a murine model of allergen‐induced sensitization and airway inflammation
Authors: Stock Philippe , Kallinich Tilmann , Akbari Omid , Quarcoo David , Gerhold Kerstin , Wahn Ulrich , Umetsu Dale T. , Hamelmann Eckard
Published: May 2004

The role of CD8+ T cells in the development of allergic airway disease is controversial. On the one hand, CD8+ T cells are known to inhibit the development of airway hyperreactivity (AHR) in murine models of asthma. In humans, IL‐10‐producing CD8+ T cells were shown to act as regulatory cells, inhibiting both proliferation and cytokine secretion of T cells. On the other hand, CD8+ T cells can promote IL‐5‐mediated eosinophilic airway inflammation and the development of AHR in animal models. To examine this, we investigated the role of CD8+ T cells during the induction of allergen‐induced AHR and demonstrated a protective effect of CD8+ T cells. Depletion of CD8+ T cells prior to the immunization led to increased Th2 responses and increased allergic airway disease. However, after development of AHR, CD8+ T cells that infiltrated the lungs secreted high levels of IL‐4, IL‐5 and IL‐10, but little IFN‐γ, whereas CD8+ T cells in the peribronchial lymph nodes or spleen produced high levels of IFN‐γ, but little or no Th2 cytokines. These data demonstrate protective effects of CD8+T cells against the induction of immune responses and show a functional diversity of CD8+ T cells in different compartments of sensitized mice.
CD95 death‐inducing signaling complex formation and internalization occur in lipid rafts of type I and type II cells
Authors: Eramo Adriana , Sargiacomo Massimo , Ricci‐Vitiani Lucia , Todaro Matilde , Stassi Giorgio , Messina Carlo G. M. , Parolini Isabella , Lotti Fiorenza , Sette Giovanni , Peschle Cesare , De Maria Ruggero
Published: May 2004

We investigated the membrane localization of CD95 in type I and type II cells, which differ in their ability to recruit and activate caspase‐8. We found that CD95 was preferentially located inlipid rafts of type I cells, while it was present both in raft and non‐raft plasma membrane sub‐domains of type II cells. After stimulation, CD95 located in phospholipid‐rich plasma membrane was recruited to lipid rafts in both types of cells. Similarly, CD95 cross‐linking resulted in caspase‐independent translocation of FADD/MORT1 and caspase‐8 to the lipid rafts, which was prevented by a death domain‐defective receptor. CD95 internalization was then rapid in type I and delayed in type II cells and showed a substantial correlation with the kinetics of Fas‐associated death domain (FADD)and caspase‐8 recruitment to lipid rafts. Finally, electron microscopy analysis showed that after CD95 stimulation lipid rafts aggregated in large clusters that were internalized in endosomal vesicles, where caspase‐8 underwent massive processing. Taken together, our data demonstrate that CD95 death‐inducing signaling complex formation and internalization in type I and type II cells occur in lipidrafts, which are a major site of caspase‐8 activation.
CREB function is required for normal thymic cellularity and post‐irradiation recovery
Authors: Baumann Sven , Kyewski Bruno , Bleckmann Susanne C. , Greiner Erich , Rudolph Dorothea , Schmid Wolfgang , Ramsay Robert G. , Krammer Peter H. , Schütz Günther , Mantamadiotis Theo
Published: May 2004

Recent generation of genetically modified Creb1 mutant mice has revealed an important role for CREB (cAMP responsive element binding protein) and the related proteins CREM (cAMP responsive element modulator) and ATF1 (activating transcription factor 1) in cell survival, in agreement with previous studies using overexpression of dominant‐negative CREB (dnCREB). CREB and ATF1 are abundantly expressed in T cells and are rapidly activated by phosphorylation when T cells are stimulated through the T cell antigen receptor. We show that T cell‐specific loss of CREB in mice, in combination with the loss of ATF1, results in reduced thymic cellularity and delayed thymic recovery following sublethal irradiation but no changes in T cell development or activation. These data show that loss of CREB function has specific effects on thymic T lymphocyte proliferation and homeostasis in vivo.
A Theoretical Investigation of the Donor Ability of [M(R,R′timdt)2] Dithiolene Complexes towards Molecular Diiodine (M = Ni, Pd, Pt; R,R′timdt = Formally Monoreduced Disubstituted Imidazolidine‐2,4,5‐trithione)
Authors: Aragoni M. Carla , Arca Massimiliano , Demartin Francesco , Devillanova Francesco A. , Lelj Francesco , Isaia Francesco , Lippolis Vito , Mancini Annalisa , Pala Luca , Verani Gaetano
Published: May 2004

The σ‐type charge‐transfer (CT) interaction between [M(R,R′timdt)2] donors (M = Ni, Pd, Pt; R,R′timdt = formally monoreduced disubstituted imidazolidine‐2,4,5‐trithione) and diiodine has been thoroughly investigated by a large set of theoretical calculations at different levels of theory (HF, pure and hybrid‐DFT with different functionals and basis sets) on I2 (and for the sake of comparison on IBr and Br2), on the model donor dithiolene complexes [M(H2timdt)2], and on the adducts [M(H2timdt)2]·I2 (M = Ni, Pd, Pt). The computations have accounted for the ability of adducts to assume different stoichiometries and to make up polymeric networks based on sulfur−iodine contacts, as in the case of [Ni(Me,iPr‐timdt)2]·I2, which was also characterised by single‐crystal X‐ray diffraction. In addition, the strength of the donor−acceptor interaction has been evaluated through the calculated vibrational features of the model adducts, compared with the experimental FT‐Raman spectra recorded on the adducts between [M(Et2timdt)2] and [M(Me,iPr‐timdt)2] (M = Ni, Pd, Pt) and diiodine. The frontier‐orbital composition, the NBO‐charge distribution and bond orders indicate a medium‐weak donor ability for the dithiolene donors, which depends only slightly on the nature of the central metal ion, and decreases on passing from M = Ni to M = Pd and Pt, in agreement with the values of the experimental frequencies of the FT‐Raman‐active I−I stretching vibrations in the adducts [M(Et2timdt)2]·2I2 (M = Ni, Pd, Pt). The ZPE‐ and CP BSSE‐corrected binding energy for [Ni(H2timdt)2]·I2 has been evaluated as −11 kcal/mol. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Intermolecular Interactions between Chelate Rings and Phenyl Rings in Square‐Planar Copper(II) Complexes
Authors: Tomić Zoran D. , Novaković Sladjana B. , Zarić Snežana D.
Published: May 2004

Analysis of the geometrical parameters in crystal structures of square‐planar copper(II) complexes from the CSD shows that the short noncovalent copper(II)−phenyl carbon distances are a consequence of the interaction between the phenyl ring and the chelate ring with delocalized π‐bonds. The data show a correlation between the distances between the centers of the chelate and phenyl rings and the copper(II)−carbon distances, as well as a mutual slipped‐parallel orientation of the phenyl and chelate rings. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
An Ni4 Single‐Molecule Magnet: Synthesis, Structure and Low‐Temperature Magnetic Behavior
Authors: Moragues‐Cánovas María , Helliwell Madeleine , Ricard Louis , Rivière Éric , Wernsdorfer Wolfgang , Brechin Euan , Mallah Talal
Published: May 2004

The reaction of Ni(NO3)2·6H2O with H3thme (trihydroxymethylethane) in the presence of NaOMe leads to a tetranuclear Ni4 complex with a cubane‐like structure. Intramolecular ferromagnetic interactions [J = 10 cm−1 based on H = −J(S1·S2 + S1·S3 + S1·S4 + S2·S3 + S2·S4 + S3·S4)] lead to an S = 4 ground state stabilized by 40 cm−1 from the first S = 3 excited state. Magnetization vs. field studies at different temperatures above 2 K suggest the presence of an axial magnetic anisotropy. Single‐crystal magnetization measurements show a single‐molecule‐magnetic behavior below T = 0.5 K with fast relaxation of the magnetization due to resonant quantum tunneling. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Analysis of cellular interference for MC‐CDMA and its impact on channel estimation
Authors: Auer Gunther , Sand Stephan , Dammann Armin , Kaiser Stefan
Published: May 2004

We address the downlink of a cellular multi‐carrier CDMA (MC‐CDMA) system taking into account channel estimation. The system performance in presence of a synchronization mismatch between two interfering base stations (BS) is analyzed in the way that a mobile terminal receives the perfectly synchronized signal from the desired BS as well as the signal from one interfering BS with a synchronization offset. It is demonstrated through simulations that spreading and cell specific random subcarrier interleaving effectively decorrelates the interfering signal, independent of the synchronization offset. Furthermore, the robustness of the channel estimator to cellular interference is examined. Copyright © 2004 AEI
Efficient synchronization and power control processes for up‐link multicarrier systems based on MC‐CDMA technique
Authors: Legouable Rodolphe , Callonnec Denis , Hélard Maryline
Published: May 2004

In this paper, a new synchronization and power control process for up‐link (UL) multicarrier systems based on MC‐CDMA technique is presented. The main challenge for multicarrier systems is the time synchronization of several users who transmit data on the same OFDM symbol by using OFDMA or MC‐CDMA techniques. The aim of the UL synchronization process is to apply a global and unique fast fourier transform (FFT) to determine the data information of all users at the base station (BS). In order to allow this unique operation, estimation and correction of all the propagation delays between each user and the BS are required. This paper presents the principles of this ranging method based on the MC‐CDMA technique and the new algorithm processed at the reception side. This new algorithm is based on the differential demodulation technique and is compared to classical correlation methods applied either in the frequency or in the temporal domain in terms of performance and complexity. Copyright © 2004 AEI
Plasmid‐based short‐hairpin RNA interference in the chicken embryo
Authors: Chesnutt Catherine , Niswander Lee
Published: May 2004

Summary: The chicken neural tube serves as an ideal model for new techniques to alter gene expression. We show that short‐hairpin RNA delivered by a plasmid vector can effectively knock down expression of both exogenous and endogenous genes in the chicken neural tube. We also assay the effects of short‐hairpin RNA on the interferon response and find no difference between electroporation of a control plasmid and a short‐hairpin RNA plasmid. genesis 39:73–78, 2004. © 2004 Wiley‐Liss, Inc.
Ectopic activation of Dpp signalling in the male Drosophila germline inhibits germ cell differentiation
Authors: Bunt Stephanie M. , Hime Gary R.
Published: May 2004

The mechanisms that control differentiation of stem cells to specialised cell types probably include factors intrinsic to stem cells as well as extrinsic factors produced by the microenvironment of the stem cell niche. The Drosophila male germline is renewed from a population of stem cells located in the apical tip of the adult testis. The morphological relationship between germline stem cells and their surrounding somatic cells is well understood but the factors that regulate stem cell proliferation and differentiation are still being uncovered. This study examined the effect of stimulating Dpp signalling directly in male germ cells. Ectopic Dpp or Activin signalling resulted in overproliferation of both stem cell‐like and spermatogonial‐like cells in the apical region of the testis. A third cell population that expressed stem cell markers was seen to proliferate in the distal testis when Dpp signalling was either stimulated or repressed in germline stem cells. genesis 39:84–93, 2004. © 2004 Wiley‐Liss, Inc.
Improved generation of C57BL/6J mouse embryonic stem cells in a defined serum‐free media
Authors: Cheng Jun , Dutra Amalia , Takesono Aya , Garrett‐Beal Lisa , Schwartzberg Pamela L.
Published: May 2004

Summary: C57BL/6 is a well‐characterized mouse strain that is used extensively for immunological and neurological research. The establishment of C57BL/6 ES cell lines has facilitated the study of gene‐altered mice in a pure genetic background—however, relatively few such lines exist. Using a defined media supplement, knockout serum replacement (KSR) with knockout DMEM (KSR‐KDMEM), we find that we can readily establish ES cell lines from blastocysts of C57BL/6J mice. Six lines were established, all of which were karyotypically normal and could be maintained in the undifferentiated state on mouse embryonic fibroblast (MEF) feeders. One line was further tested and found to be karyotypically stable and germline competent, both prior to manipulation and after gene targeting. For this cell line, efficiencies of cell cloning and chimera generation were greater when maintained in KSR‐KDMEM. Our work suggests that the use of defined serum‐free media may facilitate the generation of ES cells from inbred mouse strains. genesis 39:100–104, 2004. Published 2004 Wiley‐Liss, Inc.
Lentivirally generated eGFP‐transgenic rats allow efficient cell tracking in vivo
Authors: van den Brandt Jens , Wang Dapeng , Kwon Soon‐Hwan , Heinkelein Martin , Reichardt Holger M.
Published: May 2004

Here we describe the efficient generation of eGFP‐transgenic rats using a lentiviral approach. Analysis of the founder generation demonstrated that 46% of the offspring had stably integrated the provirus into the genome and of those 92% expressed eGFP in all blood‐derived leukocytes. In contrast to their offspring, all founder rats were mosaic with regard to eGFP‐expression, suggesting delayed viral transduction after injection. The expression level of eGFP in the F1 generation is influenced by and segregates with the site of proviral integration. Interestingly, a single copy of the transgene is sufficient for reliable detection by flow cytometry, irrespective of the leukocyte subtype analyzed. Adoptive transfer of purified CD4+ T‐lymphocytes from transgenic rats and subsequent reisolation from various organs further demonstrated that expression of the lentiviral transgene is maintained in a foreign host and therefore allows for efficient tracking of transferred cells. Taken together, lentivirally generated eGFP‐transgenic rats are a powerful tool for various applications in immunology and presumably also many other fields. genesis 39:94–99, 2004. © 2004 Wiley‐Liss, Inc.
New Nonhydrolyzable Mimetics of Sialyl Lewis X and Their Binding Affinity to P‐Selectin
Authors: Carrel Frédéric , Giraud Sylvain , Spertini Olivier , Vogel Pierre
Published: May 2004

Wittig olefination of (2S,3R,5S,6R)‐5‐(acetyloxy)‐tetrahydro‐6‐[(methoxymethoxy)methyl]‐3‐(phenylthio)‐ 2H‐pyran‐2‐acetaldehyde ((+)‐10) with {2‐[(2S,3R,4R,5R,6S)‐tetrahydro‐3,4,5‐tris(methoxymethoxy)‐6‐methyl‐ 2H‐pyran‐2‐yl]ethyl}triphenylphosphonium iodide ((−)‐11) gave a (Z)‐alkene derivative (+)‐12 that was converted into (αR,2R,3S,4R,5R,6S)‐tetrahydro‐α,3‐dihydroxy‐2‐(hydroxymethyl)‐5‐(phenylthio)‐6‐{(2Z)‐4‐[(2S,3S,4R,5S,6S)‐tetrahydro‐3,4,5‐trihydroxy‐6‐methyl‐2H‐pyran‐2‐yl]but‐2‐enyl}2H‐pyran‐4‐acetic acid (8), (αR,2R,3S,4R,6S)‐tetrahydro‐α,3‐dihydroxy‐2‐(hydroxymethyl)‐6‐{4‐[(2S,3S,4R,5S,6S)‐tetrahydro‐3,4,5‐trihydroxy‐6‐methyl‐2H‐pyran‐2‐yl]butyl}‐2H‐pyran‐4‐acetic acid (9), and simpler analogues without the hydroxyacetic side chain such as (2S,3S,4R,5S,6S)‐tetrahydro‐6‐methyl‐2‐{(2Z)‐4‐[(2S,3R,5S,6R)‐tetrahydro‐5‐hydroxy‐6‐(hydroxymethyl)‐3‐(phenylthio)‐2H‐pyran‐2‐yl]but‐2‐enyl}‐2H‐pyran‐3,4,5‐triol (30), (2S,3S,4R,5S,6S)‐tetrahydro‐6‐methyl‐2‐{[(2S,5S,6R)‐tetrahydro‐5‐hydroxy‐6‐(hydroxymethyl)‐2H‐pyran‐2‐yl]butyl}‐2H‐pyran‐3,4,5‐ triol ((−)‐41) and (2S,3S,4R,5S,6S)‐tetrahydro‐6‐methyl‐2‐{(2Z/E))‐4‐[(2R,5S,6R)‐tetrahydro‐5‐hydroxy‐6‐(hydroxymethyl)‐2H‐pyran‐2‐yl]but‐2‐enyl}‐2H‐pyran‐3,4,5‐triol (43). The key intermediates (+)‐10 and (−)‐11 were derived from isolevoglucosenone and from L‐fucose, respectively. The following IC50 values were measured in a ELISA test for the affinities of sialyl Lewis x tetrasaccharide, 8, 9, 30, (−)‐41, and 43 toward P‐selectin: 0.7, 2.5–2.8, 7.3–8.0, 5.3–5.9, 5.0–5.2, and 3.4–4.1 mM, respectively.
NIR Absorbing Squaraines by Extension of the Conjugation with (Aminothiazolyl)ethenyl Groups
Authors: Meier Herbert , Petermann Ralf
Published: May 2004

The bis{4‐{2‐[2‐(dialkylamino)thiazol‐5‐yl]ethenyl}‐2,6‐dihydroxyphenyl}squaraines 12a,b were synthesized from ethyl carbonochloridate (1) in six steps (Scheme). The donor–acceptor–donor systems 12a,b are dark blue dyes with absorption maxima in the NIR region, unless the measurements are performed in the presence of EtOH. In the latter case, the long‐wavelength band disappears, and the absorption in the UV region is strongly enhanced. The λmax values in CHCl3 and CHCl3/EtOH differ by more than 450 nm. The completely reversible effect can be rationalized by the reversible degradation of intramolecular H‐bonds and a consequent torsion between the acceptor and the donor moieties.
Rubescensins S and T: Seco‐ent‐Kaurane Diterpenoids from Isodon rubescens var. taihangensis
Authors: Han Quan‐Bin , Li Rong‐Tao , Zhang Ji‐Xia , Sun Han‐Dong
Published: May 2004

Two new diterpenoids, rubescensin S (=(1α,6β,14β)‐7α,20‐epoxy‐1,7,14‐trihydroxy‐16‐oxo‐15,16‐seco‐ent‐kauran‐6,15‐olide; 1) and rubescensin T (=(1α,6β,11β,20S)‐7α,20‐epoxy‐1,6,7‐trihydroxy‐20‐methoxy‐8,15‐seco‐ent‐kaur‐16‐en‐11,15‐olide; 2) were isolated from the Chinese medicinal herb Isodon rubescens var. taihangensis. Compound 1 possesses a unique, unprecedented 15,16‐seco‐ent‐kaurane skeleton. Both compounds exhibited cytotoxic activities against K562 human leukemia cells.
Four Novel Eremophilanolides from Ligularia sagitta
Authors: Li Lyi , Xu Li‐Wen , Wang Han‐Qing
Published: May 2004

Four new eremophilanolides, isolated from Ligularia sagitta, were identified as (1β,3β,6β,8β,10β)‐6‐acetoxy‐3‐(angeloyloxy)‐1,10‐epoxy‐8‐hydroxyeremophil‐7(11)‐en‐8,12α‐olide (1), (1β,3β,6β,8β,10β)‐3‐(angeloyloxy)‐1,10‐epoxy‐6,8‐dihydroxyeremophil‐7(11)‐en‐8,12α‐olide (2), (1β,3β,6β,8β,10β)‐3‐(angeloyloxy)‐1,10‐epoxy‐8‐ethoxy‐6‐hydroxyeremophil‐7(11)‐en‐8,12α‐olide (3), and (1β,3β,8β,10β)‐3‐(angeloyloxy)‐1,10‐epoxy‐8‐hydroxyeremophil‐7(11)‐en‐8,12α‐olide (4). Their structures were elucidated by spectroscopic methods, including 2D‐NMR techniques and chemical transformations.
Iridoid and Phenylethyl Glycosides from Globularia sintenisii
Authors: Kırmızıbekmez Hasan , Çalış İhsan , Piacente Sonia , Pizza Cosimo
Published: May 2004

A new iridoid glycoside, sintenoside (1) and two new phenylethyl glycosides, globusintenoside (=2‐(3,4‐dihydroxyphenyl)ethyl‐O‐6‐O‐feruloyl‐β‐D‐glucopyranosyl‐(1→4)‐α‐L‐rhamnopyranosyl‐(1→3)‐4‐O‐caffeoyl‐β‐D‐glucopyranoside; 2) and 3′′′‐O‐methylcrenatoside (=1,2‐O‐[2‐(3,4‐dihydroxyphenyl)ethan‐1,2‐diyl]‐3‐O‐α‐L‐4‐O‐feruloyl‐rhamnopyranosyl‐β‐D‐glucopyranose; 3) were isolated from the underground parts of Globularia sintenisii, along with three known iridoid glycosides, lytanthosalin, globularin, catalpol, and six known phenylethyl glycosides, verbascoside, isoverbascoside, leucoscepthoside A, plantainoside C, martynoside, and isocrenatoside. The structure elucidation of the isolated compounds was performed by spectroscopic methods (MS and 1D and 2D NMR).
Model Studies towards the Synthesis of the Right‐Hand Part of Pederin
Authors: Rölle Thomas , Hoffmann Reinhard W.
Published: May 2004

Bicyclic acetal derivatives of the type 3 were prepared based either on a dihydroxyaldehyde 5 or an oxiranebutanal 6 (cf. Scheme 2). Lewis acid catalyzed reaction of the bicyclic acetal with allyltrimethylsilane introduces the side chain (as yet unfunctionalized) and sets the stereogenic centers at the tetrahydro‐2H‐pyran ring of the pederin moiety.
New Triterpenoidal Saponins Acylated with Monoterpenic Acid from Albizia adianthifolia
Authors: Haddad Mohamed , Miyamoto Tomofumi , Lacaille‐Dubois Marie‐Aleth
Published: May 2004

Four new triterpenoidal saponins acylated with monoterpenic acid, i.e., adianthifoliosides C, D, E, and F (1–4), besides the two known julibroside III and the monodesmonoterpenyl elliptoside A, were isolated from the roots of Albizia adianthifolia. Their structures were elucidated on the basis of extensive 1D‐ and 2D‐NMR studies and mass spectrometry as 3‐O‐{O‐α‐L‐arabinopyranosyl‐(1→2)‐O‐β‐d‐fucopyranosyl‐(1→6)‐O‐[β‐d‐glucopyranosyl‐(1→2)]‐β‐d‐glucopyranosyl}‐21‐O‐{(2E,6S)‐6‐{{4‐O‐[(2E,6S)‐2,6‐dimethyl‐6‐(β‐D‐quinovopyranosyloxy)octa‐2,7‐dienoyl]‐β‐d‐quinovopyranosyl}oxy}‐2‐(hydroxymethyl)‐6‐methylocta‐2,7‐dienoyl}acacic acid 28‐{O‐α‐L‐arabinofuranosyl‐(1→4)‐O‐[β‐d‐glucopyranosyl‐(1→3)]‐O‐α‐L‐rhamnopyranosyl‐(1→2)‐β‐d‐glucopyranosyl} ester (1), 21‐O‐{(2E,6S)‐6‐{{4‐O‐[(2E,6S)‐2,6‐dimethyl‐6‐(β‐d‐quinovopyranosyloxy)octa‐2,7‐dienoyl]‐β‐d‐quinovopyranosyl}oxy}‐2‐(hydroxymethyl)‐6‐methylocta‐2,7‐dienoyl}‐3‐O‐{O‐β‐D‐xylopyranosyl‐(1→2)‐O‐β‐d‐fucopyranosyl‐(1→6)‐2‐(acetylamino)‐2‐deoxy‐β‐d‐glucopyranosyl}acacic acid 28‐{O‐α‐L‐arabinofuranosyl‐(1→4)‐O‐[β‐d‐glucopyranosyl‐(1→3)]‐O‐α‐L‐rhamnopyranosyl‐(1→2)‐β‐d‐glucopyranosyl} ester (2), 21‐O‐{(2E,6S)‐6‐{{3‐O‐[(2E,6S)‐2,6‐dimethyl‐6‐(β‐d‐quinovopyranosyloxy)octa‐2,7‐dienoyl]‐β‐d‐quinovopyranosyl}oxy}‐2,6‐dimethylocta‐2,7‐dienoyl}‐3‐O‐{O‐β‐D‐xylopyranosyl‐(1→2)‐O‐β‐d‐fucopyranosyl‐(1→6)‐2‐(acetylamino)‐2‐deoxy‐β‐d‐glucopyranosyl}acacic acid 28‐{O‐α‐L‐arabinofuranosyl‐(1→4)‐O‐[β‐d‐glucopyranosyl‐(1→3)]‐O‐α‐L‐rhamnopyranosyl‐(1→2)‐β‐d‐glucopyranosyl} ester (3), and 3‐O‐{O‐α‐L‐arabinopyranosyl‐(1→2)‐O‐β‐d‐fucopyranosyl‐(1→6)‐O‐[β‐d‐glucopyranosyl‐(1→2)]‐β‐d‐glucopyranosyl}‐21‐O‐{(2E,6S)‐2,6‐dimethyl‐6‐(β‐d‐quinovopyranosyloxy)octa‐2,7‐dienoyl}acacic acid 28‐{O‐α‐L‐arabinofuranosyl‐(1→4)‐O‐[β‐d‐glucopyranosyl‐(1→3)]‐O‐α‐L‐rhamnopyranosyl‐(1→2)‐β‐d‐glucopyranosyl} ester (4).
Hydrolytic Reaction of Plant Extracts to Generate Molecular Diversity: New Dammarane Glycosides from the Mild Acid Hydrolysate of Root Saponins of Panax notoginseng
Authors: Teng Rong‐Wei , Li Hai‐Zhou , Wang De‐Zu , Yang Chong‐Ren
Published: May 2004

Molecular diversity was generated by hydrolyzing the crude root saponins of Panax notoginseng (Burk.) F. H. Chen under mild acidic condition (AcOH/EtOH 1 : 1). From the acid hydrolysate, five new dammarane glycosides, named notoginsenoside T1 (=(3β,6α,12β,20E,23RS)‐24,25‐epoxy‐6‐[(β‐D‐glucopyranosyl)oxy]‐dammar‐20(22)‐ene‐3,12,23‐triol; 1), notoginsenoside T2 (=(3β,6α,12β,20E,23RS)‐24,25‐epoxy‐6‐[(β‐D‐glucopyranosyl)oxy]‐23‐methoxydammar‐20(22)‐ene‐3,12‐diol; 2), notoginsenoside T3 (=(3β,6α,12β,20S)‐6‐[(β‐D‐glucopyranosyl)oxy]‐20‐ethoxydammar‐24‐ene‐3,12‐diol; 3), notoginsenoside T4 (=(3β,6α,12β,20S,22E,24RS)‐6‐[(β‐D‐glucopyranosyl)oxy]dammar‐22‐ene‐3,12,20,24,25‐pentol; 4), and notoginsenoside T5 (=(3β,6α,12β, 24E)‐6‐[(β‐D‐xylopyranosyl‐(1→2)‐β‐D‐glucopyranosyl)oxy]dammara‐20(21),24‐diene‐3,12‐diol; 5), were isolated, together with 15 known dammarane glycosides, and their structures were elucidated on the basis of spectroscopic evidence. Among the known compounds, ginsenosides Rg3 and Rh1 were isolated as major constituents, in addition to ginsenosides Rg5, Rh4, and a mixture of (20R)‐ and (20S)‐25‐hydroxyginsenoside Rh1, all of which were obtained from P. notoginseng for the first time.
SPARC and tumor growth: Where the seed meets the soil?
Authors: Framson Paul E. , Sage E. Helene
Published: May 2004

Matricellular proteins mediate interactions between cells and their extracellular environment. This functional protein family includes several structurally unrelated members, such as SPARC, thrombospondin 1, tenascin C, and osteopontin, as well as some homologs of these proteins, such as thrombospondin 2 and tensascin X. SPARC, a prototypic matricellular protein, and its homolog hevin, have deadhesive effects on cultured cells and have been characterized as antiproliferative factors in some cellular contexts. Both proteins are produced at high levels in many types of cancers, especially by cells associated with tumor stroma and vasculature. In this Prospect article we summarize evidence for SPARC and hevin in the regulation of tumor cell growth, differentiation, and metastasis, and we propose that matricellular proteins such as these perform critical functions in desmoplastic responses of tumors that culminate in their dissemination and eventual colonization of other sites. © 2004 Wiley‐Liss, Inc.
Application of mass spectrometry to the identification and quantification of histone post‐translational modifications
Authors: Freitas Michael A. , Sklenar Amy R. , Parthun Mark R.
Published: May 2004

The core histones are the primary protein component of chromatin, which is responsible for the packaging of eukaryotic DNA. The NH2‐terminal tail domains of the core histones are the sites of numerous post‐translational modifications that have been shown to play an important role in the regulation of chromatin structure. In this study, we discuss the recent application of modern analytical techniques to the study of histone modifications. Through the use of mass spectrometry, a large number of new sites of histone modification have been identified, many of which reside outside of the NH2‐terminal tail domains. In addition, techniques have been developed that allow mass spectrometry to be effective for the quantitation of histone post‐translational modifications. Hence, the use of mass spectrometry promises to dramatically alter our view of histone post‐translational modifications. © 2004 Wiley‐Liss, Inc.
Antennal sensilla of two parasitoid wasps: A comparative scanning electron microscopy study
Authors: Bleeker Maartje A.K. , Smid Hans M. , Van Aelst Adriaan C. , Van Loon Joop J.A. , Vet Louise E.M.
Published: May 2004

Two closely related parasitoid wasp species, Cotesia glomerata (L.) and Cotesia rubecula (Marshall) (Hymenoptera:Braconidae), are different in their associative learning of plant odors. To provide a solid basis for our research on the mechanisms that underlie this difference, we described the morphology of the antennal sensilla of these two species using scanning electron microscopy complemented with transmission electron microscopy. Female and male antennae of both species have the same six types of sensilla. We classified these sensilla as sensilla trichodea without pores, sensilla trichodea with a tip pore, sensilla trichodea with wall pores, sensilla coeloconica type I, sensilla coeloconica type II, and sensilla placodea. We conclude that the morphology, numbers, and distribution of the sensory receptors are highly similar in these two closely related wasp species. Differences between species and sexes occurred only in sensilla placodea numbers. C. rubecula has more sensilla placodea than C. glomerata and males of both species have a larger number and a higher density of sensilla placodea compared to females of the same species. Microsc. Res. Tech. 63:266–273, 2004. © 2004 Wiley‐Liss, Inc.
Fluorescence shell: A novel view of sclereid morphology with the Confocal Laser Scanning Microscope
Authors: Angeles Guillermo , Owens Shirley A. , Ewers Frank W.
Published: May 2004

Confocal Laser Scanning Microscopy (CLSM) was used to observe sclereids from stems of Avicennia germinans and from fruits of two species of pear (Pyrus calleryana “Bradford” and P. communis “Red Bartlett”). The images obtained from thick (25 to 100 μm) free‐hand sections were, in certain respects, far superior to those obtained by other, more invasive and time‐consuming microscopic techniques upon which previous reports of sclereid morphology were based. The cell wall surfaces, including the “internal” surfaces of the branched pit canals and cell lumens, were much accentuated with the techniques we describe, resulting in a “fluorescence shell” image, meaning the cell wall did not stain all the way through but instead only at the inner and outer wall surfaces, including the edges of ramiform pits. By controlling the time of staining with 1% aqueous Safranin O, or by changing the number of optical sections used in extended focus images, it was possible to get either a conventional view of the cell wall structure or a unique, three‐dimensional view of the elaborate cell interconnections. Similar fluorescence shell images of sclereids were also obtained using a periodic‐Schiff (PAS) staining system, but the stain was not as specific to sclereid cell walls as was the Safranin O stain. Particularly with the use of a narrow range band pass emission filter of 505–530 nm, the Safranin O staining may be more specific to lignin than reported in the literature. Microsc. Res. Tech. 63:282–288, 2004. © 2004 Wiley‐Liss, Inc.
The risk of hyponatremia in older adults using desmopressin for nocturia: A systematic review and meta‐analysis
Authors: Weatherall Mark
Published: May 2004

Aims

To estimate the incidence of hyponatremia in older adults who use nasal or oral desmopressin to treat nocturia.

Materials and Methods

A systematic review and meta‐analysis of cohort studies and randomised controlled trials of the use of nasal or oral desmopressin for older adults with nocturia. The incidence of hyponatremia was estimated by a random effects model for binomial data.

Results

Seventy‐five papers were identified by the literature review of which 14 were reports of randomised trials or cohort studies. Seven studies reported the incidence of hyponatremia. The pooled estimate for the incidence of hyponatremia was 7.6% (95% CI 3.7–15.1).

Conclusions

Hyponatremia is a relatively common adverse effect of the use of desmopressin for the treatment of nocturia and caution and regular monitoring should be part of the use of this management option for nocturia in older adults. © 2004 Wiley‐Liss, Inc.
The reproducibility of urodynamic findings in healthy female volunteers: Results of repeated studies in the same setting and after short‐term follow‐up
Authors: Gupta Amit , Defreitas Gina , Lemack Gary E.
Published: May 2004

Aim

To assess the immediate (same testing period) and short‐term (within 6 months) repeatability of urodynamic (UD) testing in asymptomatic healthy female volunteers.

Materials and Methods

Twenty asymptomatic women with a mean age of 41.8 years (30–55) agreed to undergo a UD assessment which consisted of noninvasive uroflowmetry, post‐void residual (PVR) measurement, medium‐fill cystometry, and pressure flow study with perineal surface electromyographic (EMG) electrodes. The UDS evaluation was repeated immediately without removing the catheters (a two‐fill and void study). Sixteen women returned for an identical UD assessment 1–5 months later. Immediate and short‐term repeatability of UD parameters was assessed by calculating the coefficient of repeatability (COR).

Results

The repeatability of certain parameters of immediate UD testing could not be calculated since there was an apparent influence of the first test on the second (i.e., an apparent accommodation noted in bladder filling volumes). Other immediate UD values (maximum flow, detrusor pressure at maximum flow, voided volume) had high COR values, as did all UD values on short‐term testing, indicating relatively poor repeatability. Picking the ‘best’ pressure flow value (highest flow rate with accompanying detrusor pressure) did not consistently improve the COR values.

Conclusions

The lack of repeatability of UD studies likely stems from a combination of the true physiological fluctuations in bladder function and the inherent relative insensitivity of our instruments in conducting these testing. Knowledge of the limitations of current technology is essential in allowing us to better utilize these studies in evaluating our patients and further improving diagnostic strategies. © 2004 Wiley‐Liss, Inc.
ICIQ: A brief and robust measure for evaluating the symptoms and impact of urinary incontinence
Authors: Avery Kerry , Donovan Jenny , Peters Tim J. , Shaw Christine , Gotoh Momokazu , Abrams Paul
Published: May 2004

Aims

To develop and evaluate the International Consultation on Incontinence Questionnaire (ICIQ), a new questionnaire to assess urinary incontinence and its impact on quality of life (QoL).

Methods

A developmental version of the questionnaire was produced following systematic literature review and views of an expert committee and patients. Several studies were undertaken to evaluate the psychometric properties of the questionnaire, including content, construct and convergent validity, reliability and sensitivity to change.

Results

The ICIQ was easily completed, with low levels of missing data (mean 1.6%). It was able to discriminate among different groups of individuals, indicating good construct validity. Convergent validity was acceptable, with most items demonstrating ‘moderate’ to ‘strong’ agreement with other questionnaires. Reliability was good, with ‘moderate’ to ‘very good’ stability in test‐retest analysis and a Cronbach's alpha of 0.95. Items identified statistically significant reductions in symptoms from baseline following surgical and conservative treatment. Item reduction techniques were used to determine the final version and scoring scheme, which also demonstrated good psychometric properties.

Conclusions

The final ICIQ comprises three scored items and an unscored self‐diagnostic item. It allows the assessment of the prevalence, frequency, and perceived cause of urinary incontinence, and its impact on everyday life. The ICIQ is a brief and robust questionnaire that will be of use in outcomes and epidemiological research as well as routine clinical practice. © 2004 Wiley‐Liss, Inc.
How reliable are bladder perceptions during cystometry?
Authors: Erdem Erim , Akbay Erdem , Doruk Erdal , Çayan Selahittin , Acar Deniz , Ulusoy Ercüment
Published: May 2004

Aims

Sensory input is important for bladder control in daily life. It has been reported that perceptions during cystometry are subjective. To help refine this subjectivity, objective and semi‐objective tests (e.g., sensory thresholds of electrical stimulation) have been recommended by The International Continence Society. However, the reliability of such studies has not been established. This study was designed to evaluate the reliability of bladder perceptions during cystometry.

Methods

The study included 59 patients with urologic complaints. The average age of 40 male and 19 female patients was 58.1 years (range: 14–83). After insertion of an 8F double lumen catheter, patients were blinded to the pump and screen process. During Phase I nothing was infused. In Phase II, filling cystometry was performed with 50 ml/min pump speed and then the bladder was emptied. Phase III was performed with the same method used in Phase I. The time that each sensation was perceived, in seconds, was used to compare sensations. The bladder volume, at which sensations were perceived, was recorded at Phase II.

Results

Except for strong desire, there were no statistically significant differences between the mean times in seconds elapsed till sensations in Phases I and III, but they were different from those in Phase II. The time elapsed until strong desire was not different in each of the three phases. However, there was strong a correlation in the ratios of sensations to strong desire between Phase I and II (r = 1, P = 0.01), Phase I and III (r = 0.99, P = 0.01), and Phase II and III (r = 0.98, P = 0.01).

Conclusions

Proprioception of the bladder filling during cystometry is subjective. This data shows that sensations noticed by the patient during filling cystometry may be related to stimuli other than bladder filling. © 2004 Wiley‐Liss, Inc.
A stochastic integer programming approach to solving a synchronous optical network ring design problem
Authors: Smith J. Cole , Schaefer Andrew J. , Yen Joyce W.
Published: May 2004

We develop stochastic integer programming techniques tailored toward solving a Synchronous Optical Network (SONET) ring design problem with uncertain demands. Our approach is based on an L‐shaped algorithm, whose (integer) master program prescribes a candidate network design, and whose (continuous) subproblems relay information regarding potential shortage penalty costs to the ring design decisions. This naive implementation performs very poorly due to two major problems: (1) the weakness of the master problem relaxations, and (2) the limited information passed to the master problem by the optimality cuts. Accordingly, we enforce certain necessary conditions regarding shortage penalty contributions to the objective function within the master problem, along with a corresponding set of valid inequalities that improves the solvability of the master problem. We also show how a nonlinear reformulation of the model can be used to capture an exponential number of optimality cuts generated by the linear model. We augment these techniques with a powerful upper‐bounding heuristic to further accelerate the convergence of the algorithm, and demonstrate the effectiveness of our methodologies on a test bed of randomly generated stochastic SONET instances. © 2004 Wiley Periodicals, Inc. NETWORKS, Vol. 44(1), 12–26 2004
Management‐capacity building in the Pittsburgh region
Authors: Kearns Kevin P.
Published: May 2004

This article describes the strategy for management‐capacity building employed by The Forbes Funds in Pittsburgh, Pennsylvania. Like many other cities, Pittsburgh's capacity‐building industry has grown dramatically in recent years and is somewhat fragmented. But The Forbes Funds, along with other philanthropic organizations, have played an important role in developing a coherent system of management support services for nonprofit organizations in the Pittsburgh area. The article concludes with lessons that can be applied in other regions of the country.
A comparison of red blood cell thiopurine metabolites in children with acute lymphoblastic leukemia who received oral mercaptopurine twice daily or once daily: A Pediatric Oncology Group study (now The Children's Oncology Group)
Authors: Bell B.A. , Brockway G.N. , Shuster J.J. , Erdmann G. , Sterikoff S. , Bostrom B. , Camitta B.M.
Published: May 2004

Introduction

Mercaptopurine is an important antimetabolite for treatment of childhood acute lymphoblastic leukemia (ALL). It has been prescribed to be given daily without therapeutic monitoring of drug levels. After first‐pass metabolism by hepatic xanthine oxidase (XO), mercaptopurine is converted into two major intracellular metabolites, thioguanine nucleotide (TGN) and methylated mercaptopurine metabolites (including methylated thioinosine nucleotides), which are cytotoxic in vitro. Its short plasma half‐life and S‐phase‐dependent pharmacokinetics suggest that biologically active concentration and exposure duration may be critical to cell kill.

Methods

Pediatric Oncology Group (POG) 9605, a randomized, open label phase III study of standard‐risk ALL, was designed to compare daily with twice‐daily mercaptopurine during continuation therapy. Red blood cell (RBC) TGN and methylated mercaptopurine metabolite levels were measured as surrogates of leukemic cell levels in a randomly selected subset of patients. TGN and methylated mercaptopurine metabolites were analyzed quantitatively by high‐performance liquid chromatography (HPLC) and reported in ng/8 × 10.8 RBC. Statistical inferences utilized multiple linear regression.

Results

One hundred eighteen patients received mercaptopurine 75 mg/m2 daily and 108 received 37.5 mg/m2/dose twice daily. Descriptive statistics for the daily group showed the median TGN was 42 ng (mean and standard deviation [SD] = 48 ± 35, quartiles 29–64). For the twice daily group, it was 40 ng (mean and SD = 40 ± 27, quartiles 26–53). For methylated mercaptopurine metabolites, the daily group median was 2,020 ng (mean and SD = 2,278 ± 1,559, quartiles 1,247–3,162); the twice daily group median was 1,275 ng (mean and SD = 1,580 ± 1,240, quartiles 599–2,369). When adjusted for the covariables: actual dosage, days on study, age at diagnosis, white blood cell count, gender, Black race compared with not, and Hispanic compared with not, daily dosing resulted in significantly higher average methylated mercaptopurine metabolites by 668 (standard error [SE] = 179, P = 0.001) and a trend toward higher average TGNs by 6.2 (SE = 4.2, P = 0.14).

Conclusions

Daily dosing of mercaptopurine resulted in higher mean red cell methylated mercaptopurine metabolites when compared to split (twice a day dosing). The data were inconclusive with respect to TGNs. The relationships of methylated mercaptopurine metabolites and TGNs to clinical outcomes will be elucidated as part of the maturing 9605 data. © 2004 Wiley‐Liss, Inc.
Quality‐adjusted survival: A rigorous assessment of cure after cancer during childhood and adolescence
Authors: Barr Ronald D. , Sala Alessandra
Published: May 2004

Survivors of cancer in childhood and adolescence, while increasing gratifyingly in number with ever more effective therapy, have a life expectancy that is compromised all‐too‐often in both duration and value as a result of adverse treatment‐related sequelae. Accounting for this burden of morbidity and mortality is essential for a proper appreciation of cure. Adjusting estimates of survival by measures of its quality affords a means of accomodating this requirement. It can be accomplished by “weighting” the length of survival according to preference‐based assessments of health‐related quality of life (HRQL), which allow the calculation of quality‐adjusted life years. Inclusion of measures of HRQL in clinical trials is imperative as we reach to the ultimate objective; the truly cured child restored to normal health. © 2004 Wiley‐Liss, Inc.
Prospective audit of the introduction of insulin glargine (Lantus) into clinical practice in type 1 diabetes
Authors: Gallen I , Carter C
Published: May 2004

The aim of this study was to test whether the reported therapeutic benefits of insulin glargine over older basal insulins are also observed in routine clinical practice.

Eighty‐five people with type 1 diabetes were transferred from isophane insulin to insulin glargine between August and December 2002. Selection indications included nocturnal hypoglycaemia, fasting hyperglycaemia, the need for two isophane injections, unusual patterns of receiving insulin therapy or a personal desire to receive insulin glargine. Subject details, including glycaemic control (glucose concentrations and HbA1c levels), were recorded. Questionnaires on the frequency of all hypoglycaemic and severe hypoglycaemic episodes (requiring assistance from a third party) were recorded. Assessments on treatment satisfaction (Diabetes Treatment Satisfaction Questionnaire [DTSQ]), quality of life and well‐being (Well‐being Questionnaire 28 [W‐BQ28]) were also performed. Subjects were re‐assessed after receiving insulin glargine for six months.

Morning blood glucose concentrations and HbA1c levels fell significantly, from 9.87±0.39 to 7.93±0.29 mM (p<0.001) and from 8.24±0.12 to 7.89±0.11 (p=0.001), respectively. Total hypoglycaemic episodes remained unchanged after transferral to insulin glargine, but the number of severe hypoglycaemic episodes fell from 18 to two (p=0.002). Aggregate DTSQ scores improved from 23.7±0.85 to 28.1±0.87 (p<0.001). Perceived energy levels, diabetes specific well‐being and total well‐being each improved significantly (p<0.001, p=0.006 and p=0.032, respectively).

This study indicates that the therapeutic benefits of insulin glargine reported in clinical trials in type 1 diabetes are also observed in routine clinical practice. Copyright ©2004 John Wiley & Sons, Ltd.
Thiol‐catalysed hydrolysis of cephalosporins and possible rate‐limiting amine anion expulsion
Authors: Llinás Antonio , Vilanova Bartolomé , Page Michael I.
Published: May 2004

The rates of thiolysis of cephalosporins were investigated by high‐performance liquid chromatography and1H NMR spectroscopy. Thiols catalyse the hydrolysis through the formation of a thioester intermediate and the catalytically reactive form of the thiol is the thiolate anion. Variation of nucleophilic reactivity by changing the basicity of the thiolate anion generates a Brønsted βnucvalue of 1.22 with cephaloridine, indicating that the breakdown of the tetrahedral intermediate is the rate‐limiting step. The effect of C3′ substituents on the rate of thiolysis of cephalosporins generates a large Hammett ρ of ca 12, which is compatible with C—N bond fission occurring without protonation of the β‐lactam nitrogen. Solvent kinetic isotope effectsk/kof ca 1.1 also indicate that solvent water probably does not act as a general acid catalyst facilitating breakdown of the tetrahedral intermediate by protonating the departing amine. Copyright © 2004 John Wiley & Sons, Ltd.
The path to the transition state in enzyme reactions: a survey of catalytic efficiencies
Authors: Snider Mark G. , Temple Brenda S. , Wolfenden Richard
Published: May 2004

A survey of kcat/Km values supports the view that most enzymes combine with substrates at rates that approach the limits imposed by diffusional encounter. The closeness of that approach precludes the obligate participation of any rare species of the substrate, or any rare species of the enzyme, in productive binding. Proceeding from the ground state through the transition state, the enzyme–substrate complex is assumed to remain in a state of quasi‐equilibrium with the free enzyme and the unbound substrate in solution. Because the forces of attraction between an enzyme and substrate approach a maximum in the transition state for substrate transformation, the enzyme and substrate are also likely to approach a maximal state of distortion from their native ground‐state structures at that stage in the reaction, furnishing a natural explanation of induced fit. There is now abundant evidence, from mutations of enzymes and substrates, that interactions between the enzyme and substrate, using ordinary chemical forces of attraction, are so strongly synergistic that they may suffice to explain the very high affinities that are achieved in the transition state. Copyright © 2004 John Wiley & Sons, Ltd.