bluuebunny/crossref_metadata_2025 huggingface dataset:
Highly Selective Biphasic Telomerization of Butadiene with Glycols: Scope and Limitations
Authors: Behr Arno , Urschey Michael
Published: November 2003

Highly selective telomerization reactions of a number of short‐chain glycol nucleophiles with 1,3‐butadiene have been achieved in aqueous biphasic systems employing the water‐soluble catalyst system Pd(acac)2/TPPTS. For all substrates the selectivity for the obtained monotelomers 5–7 reached ≥95% whereas butadiene dimers 3, octadienols 4 and ditelomers like 2 were produced only in trace amounts. The order of reactivity is ethylene glycol>>1,3‐propylene glycol ≈ glycerol>1,4‐butylene glycol, which is in agreement with generally observed trends. The scope and limitations of these reactions are discussed in terms of obtained yields and achievable catalyst productivities (total turnover numbers).
Simple, Mild, and Practical Esterification, Thioesterification, and Amide Formation Utilizing p‐Toluenesulfonyl Chloride and N‐Methylimidazole
Authors: Wakasugi Kazunori , Iida Akira , Misaki Tomonori , Nishii Yoshinori , Tanabe Yoo
Published: November 2003

We have developed an efficient method for the esterification or thioesterification of equimolar amounts of carboxylic acids and alcohols or thiols using a novel reagent, p‐toluenesulfonyl chloride (TsCl) together with N‐methylimidazole. The present method is simple, mild, and reactive, uses readily available and economical reagents. The choice of amine is critical for the present method. The amine, N‐methylimidazole, has two roles: (i) as an HCl scavenger for the initial smooth generation of mixed anhydrides between carboxylic acids and TsCl and (ii) successive formation of highly reactive ammonium intermediates from mixed anhydrides. This method could be applied to various types of carboxylic acids, alcohols, and thiols: a) several functionalities were tolerated; b) two N‐Cbz amino acids were smoothly esterified without racemization; and c) the labile 1β‐methylcarbapenem key intermediate and a pyrethroid insecticide, prallethrin, were successfully prepared. The related amide formation between carboxylic acids and primary or secondary amines was also performed. The proposed reaction mechanism involves a novel method for producing the reactive acylammonium intermediates. The production of these intermediates was rationally supported by a careful 1H NMR monitoring study.
Efficient Asymmetric Synthesis of 2,6‐Disubstituted 2H‐Dihydropyrans via a Catalytic Hetero‐Diels–Alder/Allylboration Sequence
Authors: Deligny Michael , Carreaux François , Toupet Loïc , Carboni Bertrand
Published: November 2003

[4+2] Cycloaddition of (E)‐3‐borylacrolein 1 with ethyl vinyl ether, catalysed by chromium complex (1R,2S) or (1S,2R) 2, led to the corresponding cycloadducts with high diastereo‐ and enantioselectivities. Further reaction with aldehydes offers an attractive asymmetric route to synthetically useful substituted 3,4‐dihydro‐2H‐pyrans.
Chemie der Atomlagenabscheidung (Atomic Layer Deposition): jüngste Entwicklungen
Authors: Leskelä Markku , Ritala Mikko
Published: November 2003

Neue Materialien, z. B. High‐k‐Dielektrika als Ersatz für SiO2 , Cu als Ersatz für Al und Sperrschichtmaterialien für Cu, revolutionieren die Fertigung moderner integrierter Schaltungen. Entscheidend dabei ist, dass diese Materialien als sehr dünne Filme auf strukturierten Oberflächen abgeschieden werden müssen. Der selbstkontrollierende Wachstumsmechanismus bei der Atomlagenabscheidung (Atomic Layer Deposition, ALD) erleichtert die Steuerung der Filmdicke auf atomarer Ebene und ermöglicht eine Abscheidung auf großen und komplexen Oberflächen. Diese Eigenschaften machen die ALD zu einem vielversprechenden Verfahren zur Fertigung von integrierten Schaltungen, optischen Bauelementen, magnetischen Schreibköpfen und mikroelektromechanischen Systemen. Eine Schlüsselrolle, insbesondere bei der Auswahl der geeigneten Materialvorstufen, spielt die Chemie.
Identification of biochemical markers linked to neonicotinoid cross resistance in Bemisia tabaci (Hemiptera: Aleyrodidae)
Authors: Rauch Natascha , Nauen Ralf
Published: November 2003

The whitefly, Bemisia tabaci (Hemiptera: Aleyrodidae), is a serious pest in many cropping systems world‐wide and occurs in different biotypes. The most widespread one is the B‐type, whereas the Q‐biotype is nowadays still mostly restricted to Southern Spain. Neonicotinoid cross‐resistance is known at a high level in Q‐types from Spain and individual samples collected in Italy and Germany. Now we detected for the first time high neonicotinoid cross‐resistance in a B‐type from Israel. Target site resistance to imidacloprid using [3H]imidacloprid in nicotinic acetylcholine receptor (nAChR) binding assays could not be detected in any of these highly resistant strains. The impact of metabolizing enzymes such as esterases, glutathione S‐transferases, and cytochrome P450‐dependent monooxygenases in neonicotinoid resistance was studied biochemically with artificial substrates. Monooxygenase activity was increased 2–3‐fold in moderately resistant strains (RF ∼30) and even 5–6‐fold in highly resistant strains (RF ∼1,000). Only monooxygenase activity correlated with imidacloprid, thiamethoxam and acetamiprid resistance and, therefore, monooxygenases seem to be the only enzyme system responsible for neonicotinoid resistance in B. tabaci Q‐ and B‐types. The oxidative degradation of imidacloprid in resistant Q‐type strains could be confirmed by metabolism studies of [14C]imidacloprid in vivo. Five‐hydroxy‐imidacloprid could be detected as the only main metabolite. The insecticidal activity and binding affinity to nAChR of this compound was 10 times lower than imidacloprid itself in B. tabaci. Arch. Insect Biochem. Physiol. 54:165–176, 2003. © 2003 Wiley‐Liss, Inc.
Inheritance of pyriproxyfen resistance in the whitefly, Bemisia tabaci (Q biotype)
Authors: Horowitz, A. Rami , Gorman Kevin , Ross Gavin , Denholm Ian
Published: November 2003

The inheritance of resistance to pyriproxyfen, an insect growth regulator (a juvenoid, with ovicidal and larvicidal activities), was studied in the whitefly Bemisia tabaci (Gennadius). Two parental strains, both belonging to Q biotype, were assayed with pyriproxyfen; a susceptible strain (ALM‐1) originating from Spain and a pyriproxyfen‐resistant one (Pyri‐R) from Israel. The resistance ratio between the two parental strains was approximately 7,000‐fold. Concentration‐mortality lines for F1 heterozygous females from reciprocal crosses (SS♀ X R♂ and RR♀ X S♂) were derived by statistical modelling and proved intermediate to those of the parents. The pooled degree of dominance from both reciprocal crosses was +0.26, indicating that resistance was incompletely or partially dominant. Mortality curves for F2 males produced by virgin F1 heterozygous females displayed a broad plateau at 50% mortality, indicating that resistance to pyriproxyfen in B. tabaci is conferred primarily by a mutant allele at a single locus. The role of arrhenotoky in influencing the mode of inheritance of resistance, and its selection in field populations, is discussed. Arch. Insect Biochem. Physiol. 54:177–186, 2003. © 2003 Wiley‐Liss, Inc.
Tryptophan as a probe for acid–base equilibria in peptides
Authors: Marquezin Cássia Alessandra , Hirata Izaura Yoshico , Juliano Luiz , Ito Amando Siuiti
Published: November 2003

We present results of time resolved fluorescence measurements performed in Tryptophan (Trp) derivatives and Trp‐containing peptides in the pH range 3.0–11.0. For each compound a set of decay profiles measured in a given range of pH values was examined as a whole, using the global analysis technique. The data were fitted to two or three lifetime components and the analysis allowed the monitoring of the changes in the concentration of the different species contributing to the total fluorescence in that pH interval. The decay components were sensitive to the ionization state of groups neighboring the indol ring, and pK values for the equilibrium between protonated and deprotonated species were obtained from the preexponential factor of the lifetime components. In Trp, protonation of the amino terminal of the rotamer having electron transfer rate comparable to fluorescence decay rates was responsible for the interconvertion of a long lifetime component, to the 2.9 ns component usually observed in neutral pH. TrpX peptides also have a single rotamer dominating the decay that is quenched by NH. X–Trp peptides seem to be conformationally less restricted, and it is possible that rotamers interconvertion occur in high pH, increasing the population of nonquenched rotamers. Interconvertion between rotameric conformations of Trp are also present in the titration of ionizable groups in the side chain of peptides like His–Trp and Glu–Trp and control of pH is essential to the correct interpretation of fluorescence data in the study of peptides having such groups near to the Trp residue. © 2003 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 71: 569–576, 2003
Molecular dynamics simulations of Trp side‐chain conformational flexibility in the gramicidin A channel
Authors: Bingham Nathan C. , Smith Natasha E. C. , Cross Timothy A. , Busath David D.
Published: November 2003

Gramicidin A (gA) is prototypical peptide antibiotic and a model ion channel former. Configured in the solid‐state NMR β6.5‐helix channel conformation, gA was subjected to 1‐ns molecular dynamics (MD) gas phase simulations using the all‐atom charmm22 force field to ascertain the conformational stability of the Trp side chains as governed by backbone and neighboring side‐chain contacts. Three microcanonical trajectories were computed using different initial atomic velocities for each of twenty different initial structures. For each set, one of the four Trp side chains in each monomer was initially positioned in one of the five non‐native conformations (A. E. Dorigo et al., Biophysical Journal, 1999, Vol. 76, 1897–1908), the other Trps being positioned in the native state, o1. In three additional control simulations, all Trps were initiated in the native conformation. After equilibration, constraints were removed and subsequent conformational changes of the initially constrained Trp were measured. The χ1 was more flexible than χ2.1. The energetically optimal orientation, o1 (Dorigo et al., 1999), was the most stable in all four Trp positions (9, 11, 13, 15) and remained unchanged for the entire 1 ns simulation in 19 of 24 trials. Changes in χ1 from each of the 5 suboptimal states occur readily. Two of the non‐native conformations reverted readily to o1, whereas the other three converted to an intermediate state, i2. There were frequent interconversions between i2 and o1. We speculate that experimentally observed Trp stability is caused by interactions with the lipid–water interface, and that stabilization of one of the suboptimal conformations in gA, such as i2, by lipid headgroups could produce a secondary, metastable conformational state. This could explain recent experimental studies of differences in the channel conductance dispersity between gA and a Trp‐to‐Phe gA analog, gramicidin M (gM, J. C. Markham et al., Biochimica et Biophysica Acta, 2001, Vol. 1513, 185–192). © 2003 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 71: 593–600, 2003
Design of a New Mimochrome with Unique Topology
Authors: Lombardi Angela , Nastri Flavia , Marasco Daniela , Maglio Ornella , De Sanctis Giampiero , Sinibaldi Federica , Santucci Roberto , Coletta Massimo , Pavone Vincenzo
Published: November 2003

Peptide‐based metalloprotein models represent useful systems to help understand how metalloproteins can support different functions, by the use of similar metal ion cofactors. In order to shed light on the role of the protein matrix in modulating the heme properties, we developed new models: mimochromes. They are pseudo‐C2 symmetric systems, composed of two helical peptides covalently linked to the deuteroporphyrin. The use of C2 symmetry is particularly advantageous, because it simplifies the design, synthesis and characterization. However, it leaves the problem of possible diastereomeric forms. In the cobalt complex of the first derivative, mimochrome I, Λ and Δ isomers were indeed experimentally observed. All the insights derived from the CoIII–mimochrome I structure were used to obtain a re‐designed molecule, mimochrome IV. The spectroscopic characterization of the iron and cobalt derivatives suggested the presence of the Λ isomer as unique species. The NMR solution structure of the diamagnetic CoIII–mimochrome IV confirmed the ability of the molecule to adopt a unique topology, and revealed the peptide chains to be in helical conformation, as designed. The insertion of intramolecular, inter‐chain interactions was successful in favoring the formation of one of the two possible diastereomers. The stereochemically stable structure of mimochrome IV provides an attractive model for modulating the redox potential of the heme, by simple changing the peptide chain composition around the heme.
Mechanochemical Preparation of Hydrogen‐Bonded Adducts Between the Diamine 1,4‐Diazabicyclo[2.2.2]octane and Dicarboxylic Acids of Variable Chain Length: An X‐ray Diffraction and Solid‐State NMR Study
Authors: Braga Dario , Maini Lucia , de Sanctis Giorgiana , Rubini Katia , Grepioni Fabrizia , Chierotti Michele R. , Gobetto Roberto
Published: November 2003

Mechanical mixing of solid dicarboxylic acids of variable chain length HOOC(CH2)nCOOH (n = 1–7) with solid 1,4‐diazabicyclo[2.2.2]octane generates the corresponding salts or co‐crystals of the formula [N(CH2CH2)3N]‐H‐[OOC(CH2)nCOOH] (n=1–7). Preparation of the same systems from solution has been instrumental for a full characterization of the mechanochemical products by means of single‐crystal and powder‐diffraction X‐ray analyses, as well as by solid‐state NMR. The acid–base adducts, whether involving proton transfer from the COOH group to the N‐acceptor, that is having (−)O⋅⋅⋅HN(+) interactions, or the formation of neutral OH⋅⋅⋅N hydrogen bonds, show a melting point alternation phenomenon analogous to that shown by the neutral carboxylic acids. The carbon chemical shift tensors of the COOH group obtained from the sideband intensity of low speed spinning NMR spectra provide a reliable criterion for assigning the protonation state of the adducts.
Stereoselectivity of Nitrile Oxide Cycloadditions to Chiral Allylic Fluorides: Experiment and Theory
Authors: Prakesch Michael , Grée Danielle , Grée René , Carter Jennifer , Washington Ilyas , Houk K. N.
Published: November 2003

The cycloadditions of nitrile oxides with new and previously studied allylic fluorides were examined. The 1,3‐dipolar cycloaddition reactions were also investigated theoretically with density functional theory (B3LYP) based transition‐state modelling. The predictions provided reasonable agreement with experiment, indicating that both steric and electronic effects have important influences on the stereoselectivities of these reactions.
Towards Binuclear Polyaminocarboxylate MRI Contrast Agents? Spectroscopic and MD Study of the Peculiar Aqueous Behavior of the LnIII Chelates of OHEC (Ln=Eu, Gd, and Tb): Implications for Relaxivity
Authors: Nicolle Gaëlle M. , Yerly Fabrice , Imbert Daniel , Böttger Ulrike , Bünzli Jean‐Claude , Merbach André E.
Published: November 2003

We report the study of binuclear LnIII chelates of OHEC (OHEC=octaazacyclohexacosane‐1,4,7,10,14,17,20,23‐octaacetate). The interconversion between two isomeric forms, which occurs in aqueous solution, has been studied by NMR, UV/Vis, EPR, and luminescence spectroscopy, as well as by classical molecular dynamics (MD) simulations. For the first time we have characterized an isomerization equilibrium for a LnIII polyaminocarboxylate complex (LnIII=Y, Eu, Gd and Tb) in which the metal centre changes its coordination number from nine to eight, such that: [Ln2(ohec)(H2O)2]2−⇄[Ln2(ohec)]2−+2 H2O. The variable temperature and pressure NMR measurements conducted on this isomerization reaction give the following thermodynamic parameters for EuIII: K298=0.42±0.01, ΔH0=+4.0±0.2 kJ mol−1, ΔS0=+6.1±0.5 J K−1 mol−1 and ΔV0=+3.2±0.2 cm3 mol−1. The isomerization is slow and the corresponding kinetic parameters obtained by NMR spectroscopy are: k${{298\hfill \atop {\rm is}\hfill}}$=73.0±0.5 s−1, ΔH${{{\ne}\hfill \atop {\rm is}\hfill}}$=75.3±1.9 kJ mol−1, ΔS${{{\ne}\hfill \atop {\rm is}\hfill}}$=+43.1±5.8 J K−1 mol−1 and ΔV${{{\ne}\hfill \atop {\rm is}\hfill}}$=+7.9±0.7 cm3 mol−1. Variable temperature and pressure 17O NMR studies have shown that water exchange in [Gd2(ohec)(H2O)2]2− is slow, k${{298\hfill \atop {\rm ex}\hfill}}$=(0.40±0.02)×106 s−1, and that it proceeds through a dissociative interchange Id mechanism, ΔV≠=+7.3±0.3 cm3 mol−1. The anisotropy of this oblong binuclear complex has been highlighted by MD simulation calculations of different rotational correlation times. The rotational correlation time directed on the Gd–Gd axis is 24 % longer than those based on the axes orthogonal to the Gd–Gd axis. The relaxivity of this binuclear complex has been found to be low, since 1) only [Gd2(ohec)(H2O)2]2−, which constitutes 70 % of the binuclear complex, contributes to the inner‐sphere relaxivity and 2) the anisotropy of the complex prevents water molecules from having complete access to both GdIII cages; this decreases the outer‐sphere relaxivity. Moreover, EPR measurements for the GdIII and for the mixed GdIII/YIII binuclear complexes have clearly shown that the two GdIII centres interact intramolecularly; this enhances the electronic relaxation of the GdIII electron spins.
Symmetrical Electron‐Deficient Materials Incorporating Azaheterocycles
Authors: Pieterse Koen , Lauritsen Anne , Schenning Albertus P. H. J. , Vekemans Jef A. J. M. , Meijer E. W.
Published: November 2003

To investigate the potential of di‐ and tri‐azaheterocycles as building blocks for π‐conjugated materials with high electron affinity, linear oligomers incorporating pyrazine and a C3‐symmetric discotic molecule based on triazine were synthesized. The tridodecyloxyphenyl end‐capped ethynylene pyrazinylene oligomers showed remarkable solvatochroism in absorption and emission in solution. The oligomers containing one and two pyrazine rings displayed liquid crystallinity in the solid state. The largest ethynylene pyrazinylene oligomer containing three pyrazine rings had the lowest first reduction potential at −1.08 V. The triazine‐derived discotic molecule exhibited UV/Vis and fluorescence behavior comparable to that of the linear oligomers and featured a first reduction potential at −1.49 V, somewhat lower than expected.
Azolylpentazoles as High‐Energy Materials: A Computational Study
Authors: Hammerl Anton , Klapötke Thomas M. , Schwerdtfeger Peter
Published: November 2003

The structures of highly energetic substituted pentazole compounds and their decomposition to give dinitrogen and the corresponding azide were investigated by ab initio quantum chemical methods. The substituents include azolyl groups (five‐membered aromatic rings with different numbers of nitrogen atoms), CH3, CN, and F. The decomposition pathway was followed for several substituted azolyl‐ and phenylpentazoles and compared to the known experimental and theoretical results. The NMR parameters of most of the as‐yet unknown pentazole compounds were predicted. The activation energy for the decomposition increases, while the decomposition energy of the substituted pentazole decreases with greater electron‐donating character of the substituent of the pentazole. Thus, anionic pentazoles are more stable than neutral pentazoles. Methylpentazole is predicted to be among the most stable pentazoles, even though it does not contain an aromatic system.
Studies towards Simalikalactone D and Quassimarin: Construction of an Advanced Pentacyclic Intermediate
Authors: Shing Tony K. M. , Zhu Xue Y. , Yeung Yeung Y.
Published: November 2003

An advanced pentacyclic intermediate, amenable to further elaboration into the target molecules simalikalactone D and quassimarin, has been synthesized from (S)‐(+)‐carvone in 21 steps and with an overall yield of 12 %. The synthesis is efficient, stereocontrolled, enantiospecific, and chirality productive, creating eight new chiral centres in pentacycle, and should provide opportunities for rapid access to simalikalactone D analogues and other bioactive quassinoids. The reaction sequence involves a regioselective bishydroxylmethylation, a stereocontrolled epoxidation, an epoxymethano‐bridge formation, a 1,3‐sigmatropic rearrangement and an intramolecular Diels–Alder reaction as the key steps.
MD Simulations of Acyclic and Macrocyclic Gd3+‐Based MRI Contrast Agents: Influence of the Internal Mobility on Water Proton Relaxivity
Authors: Yerly Fabrice , Borel Alain , Helm Lothar , Merbach André E.
Published: November 2003

Classical molecular dynamics simulations with a force field adapted to the family of Gd3+ polyaminocarboxylate complexes have been successfully applied on two macrocyclic ([Gd(DOTA)(H2O)]− and [Gd(DO3A)(H2O)2]) and two acyclic ([Gd(DTPA)(H2O)]2− and [Gd(EGTA)(H2O)]−) complexes in aqueous solution (DOTA=1,4,7,10‐tetrakis(carboxymethyl)‐1,4,7,10‐tetraazacyclododecane, DO3A=1,4,6‐tris(carboxymethyl)‐1,4,7,10‐tetraazacyclododecane, DTPA=1,1,4,7,7‐pentakis(carboxymethyl)‐1,4,7‐triazaheptane, EGTA=1,1,10,10‐tetrakis(carboxymethyl)‐1,10‐diaza‐4,7‐dioxadecane). In both macrocylic complexes the Gd3+ coordination polyhedron remains close to a monocapped square antiprism (MSA) during the entire simulation time. For the stereolabile acyclic complexes different interconverting sets of geometries are observed: three sets close to tricapped trigonal prisms (TTP) for [Gd(EGTA)(H2O)]− and three sets intermediate between MSA and TTP (distorted C2v symmetry) for [Gd(DTPA)(H2O)]2−. The fast conformational changes observed in the acyclic complexes might weaken the hydration of the second water shell and therefore disfavour the outer‐sphere relaxivity. Moreover, the motions of the chelate observed in both acyclic complexes involve the reorientation of the symmetry elements over time. This reorientation, occurring on a picosecond timescale, can be associated with the correlation time for modulation of the zero field splitting and might participate in the electron spin relaxation mechanisms of the Gd3+ ion. The internal motion of the inner‐sphere water molecule can be quantified by the ratio τR(GDHW)/τR(GDOW) which increases slightly from 0.7 for the acyclic to 0.8 for the macrocyclic complexes. This increase for the macrocylic chelates is favourable for a higher relaxivity and can be related to their rigidity. The water exchange rate on the four complexes has been related to the steric constraint of the ligand on the inner‐sphere water molecule(s), which is inversely proportional to a geometrical descriptor, the solid angle ψ. A range of ψ values is given (2≪ψ<3.3) where the exchange should be optimal. The observations made on the picosecond timescale give general directions for the design of more efficient magnetic resonance imaging contrast agents.
Vinblastine, bleomycin, and methotrexate chemotherapy plus irradiation for patients with early‐stage, favorable Hodgkin lymphoma
Authors: Gobbi Paolo G. , Broglia Chiara , Merli Francesco , Dell'Olio Matteo , Stelitano Caterina , Iannitto Emilio , Federico Massimo , Bertè Raffaella , Luisi Dimitri , Molica Stefano , Cavalli Carla , Dezza Laura , Ascari Edoardo
Published: November 2003

BACKGROUND

The acknowledged effectiveness of vinblastine, bleomycin, and methotrexate (VBM) chemotherapy in patients with early‐stage Hodgkin lymphoma has been associated with conflicting toxicity reports.

METHODS

One hundred forty‐three patients were evaluated clinically and had favorable Stage IA or IIA Hodgkin lymphoma. Ninety‐three patients were treated with the standard VBM schedule combined with extended‐field radiotherapy (EF‐RT), leaving the choice of the therapeutic sequence free. Fifty subsequent patients were treated with a slightly modified VBM schedule (VbMp) combined with RT limited to involved fields (IF‐RT) and delivered only after the end of chemotherapy. In the VbMp schedule, intervals between cycles were 21 days instead of 28 days, bleomycin doses were reduced, small doses of prednisone were given orally, and the interval before RT was prolonged.

RESULTS

Clinical response was complete in 96% of patients who were treated with VBM plus EF‐RT and in 94% of patients who were treated with VbMp plus IF‐RT. Recurrence rates were nearly identical (12% and 11%, respectively) over necessarily different follow‐up (91 months and 33 months, respectively). Hematologic toxicity was tolerable in both trials, and pulmonary side effects were moderate in the first trial and negligible in the second. On the whole, treatment was tolerated better when RT followed chemotherapy.

CONCLUSIONS

The VBM regimen was confirmed to be effective in patients with early‐stage Hodgkin lymphoma. Administration of all cycles before RT improved tolerance; pulmonary toxicity probably is mitigated further by reduced bleomycin doses, mild prednisone therapy, and a more prolonged resting interval before RT. A slightly higher recurrence rate was expectable in the VBM plus IF‐RT trial despite the actual intensification of vinblastine and methotrexate. Cancer 2003. © 2003 American Cancer Society.
Change in smoking status after spiral chest computed tomography scan screening
Authors: Cox Lisa Sanderson , Clark Matthew M. , Jett James R. , Patten Christi A. , Schroeder Darrell R. , Nirelli Liza M. , Swensen Stephen J. , Hurt Richard D.
Published: November 2003

BACKGROUND

Cancer screening may provide a “teachable moment” for the reduction of high‐risk behaviors. The current study evaluated smoking behavior changes in current and former smokers after low‐dose, fast spiral chest computed tomography scan (CT) screening for lung carcinoma.

METHODS

The study was comprised of 901 current smokers and 574 former smokers who participated in a low‐dose, fast spiral chest CT scan screening study for lung carcinoma. Demographic, pulmonary function, screening recommendations, and smoking history variables were evaluated as predictors of self‐reported point prevalence smoking abstinence 1 year after screening.

RESULTS

Of the current smokers at baseline, 14% reported smoking abstinence at follow‐up. Older age and poorer lung function were associated with smoking abstinence. Ninety percent of former smokers reported smoking abstinence at a 1‐year of follow‐up. A longer duration of smoking abstinence at baseline was found to be predictive of abstinence in this group.

CONCLUSIONS

The 14% smoking abstinence rate was higher than would be expected for spontaneous rates of smoking cessation. Therefore, screening may provide a teachable moment for smokers. Low‐dose, fast spiral chest CT scan screening recommendations were not found to be associated with smoking behavior change in either group. Further research is needed to evaluate the potential avenues through which lung carcinoma screening can be used as an opportunity for providing effective nicotine interventions. Cancer 2003. © 2003 American Cancer Society.
Parathyroid carcinoma: Is there a role for adjuvant radiation therapy?
Authors: Munson Nathan D. , Foote Robert L. , Northcutt Robert C. , Tiegs Robert D. , Fitzpatrick Lorraine A. , Grant Clive S. , van Heerden Jonathan A. , Thompson Geoffrey B. , Lloyd Ricardo V.
Published: November 2003

BACKGROUND

The authors proposed to determine risk factors associated with postoperative progression of parathyroid carcinoma within the neck (locoregional) and to assess the efficacy of postoperative adjuvant radiation therapy in preventing disease progression within the neck.

METHODS

A retrospective review of patients with pathologically confirmed parathyroid carcinoma who underwent surgical resection was performed. Risk factors identified on univariate analysis were applied in a proportional hazards analysis to identify significant independent predictors of locoregional disease progression and cause‐specific survival after surgical resection. Fifty‐seven patients were treated with surgery alone (no adjuvant radiation therapy [RT]) and were determined to have sufficient follow‐up and pathologically confirmed features to be included in the current analysis. Four patients were treated with surgery and adjuvant RT. Four patients received RT to the neck and mediastinum for unresectable locoregional disease progression. Patients were followed for a median of 75.6 months (range, 8.4–358 months).

RESULTS

Twenty‐five patients (44%) developed locoregional disease progression at a median of 27.1 months after surgery (range, 6.2–138.3 months). The univariate analysis revealed that surgical margin status and the institution at which the initial surgery was performed were predictive of locoregional progression‐free survival. The institution at which the initial surgery was performed was found to be an independent predictor of cause‐specific survival. Of the four patients treated with surgery and adjuvant RT, all were alive and without disease at the time of last follow‐up. All four patients who received RT for locoregional disease progression after initial surgery achieved locoregional disease control.

CONCLUSIONS

Patients with parathyroid carcinoma are reported to have a significant risk of locoregional disease progression after surgery alone. The results of the current study demonstrated that the risk of postoperative disease progression can be predicted by surgical margin status and the institution at which the initial surgery is performed. Patients treated with surgery and postoperative RT may have a lower risk of locoregional disease progression and improved cause‐specific survival. RT can be used to provide locoregional control of recurrent disease. Cancer 2003. © 2003 American Cancer Society.
Clinical features of patients who present with metastatic prostate carcinoma and serum prostate‐specific antigen (PSA) levels < 10 ng/mL
Authors: Birtle Alison J. , Freeman Alex , Masters John R. W. , Payne Heather A. , Harland Stephen J. ,   Contributors to the BAUS Section of Oncology Cancer Registry
Published: November 2003

BACKGROUND

Although < 1% of men present with prostate‐specific antigen (PSA)‐negative prostate carcinoma, in that they have serum PSA levels much lower than the tumor burden would suggest, such patients represent a management dilemma. To the authors' knowledge, little information exists in the literature regarding patterns of disease and response to treatment. The authors wished to define the clinical features of this patient group.

METHODS

The British Association of Urological Surgeons Cancer Registry 2000 and 2001 data bases were used to identify the clinical features and outcome of 33 men with metastatic prostate carcinoma who presented with serum PSA levels < 10 ng/mL. Clinical notes and histopathology were reviewed for each patient.

RESULTS

Seventeen patients (51%) presented with urinary symptoms and/or pelvic pain, 6% with cachexia and 21% with bone pain. Characteristic bone metastases were present in 81% of patients, similar to the presentation of men with high serum PSA levels. Hypercalcemia was a feature in 9% of patients. Visceral metastases were present in two patients. The median response duration to first‐line hormone manipulation was 7 months. No responses were seen in 11 of 13 patients who received second‐line hormones or to any third‐line treatment. Three of 5 patients who received chemotherapy responded but developed recurrent disease within 8 weeks of treatment cessation. The median overall survival was 12 months.

CONCLUSIONS

The presentation of patients with treatment‐naïve PSA‐negative metastatic prostate carcinoma is similar to that of patients with high serum PSA levels, but their median survival and response duration to first‐line hormone therapy are of much shorter duration. Second‐line hormone therapy is ineffective, but early chemotherapy may be beneficial. Hypercalcemia is a particular feature in this group of patients. Cancer 2003. © 2003 American Cancer Society.
Is endometrial carcinoma intrinsically more aggressive in elderly patients?
Authors: Alektiar Kaled M. , Venkatraman Ennapadam , Abu‐Rustum Nadeem , Barakat Richard R.
Published: November 2003

BACKGROUND

The current study was conducted to determine the influence of old age (age ≥ 70 years) on outcome in a group of patients with endometrial carcinoma who were treated with simple hysterectomy followed by adjuvant radiation therapy (RT).

METHODS

Between November 1987 and May 2000, 405 patients with International Federation of Gynecology and Obstetrics (FIGO) Stage IB‐II endometrial carcinoma were treated with postoperative RT. Intravaginal RT alone was given to 77% of patients (median dose, 21grays [Gy] given in 3 fractions). Additional postoperative external beam radiation therapy (EBRT) was given to 23% of patients (median dose, 45 Gy). Eighty‐four patients were age ≥ 70 years and 321 patients were age < 70 years. The two groups were well balanced with regard to race, comprehensive surgical staging, aggressive histology, lymphovascular invasion, lower uterine segment involvement, cervical involvement, and the use of postoperative EBRT. Significantly more patients in the age ≥ 70 years group had other comorbidities such as obesity, diabetes mellitus, or hypertension (P= 0.02) and were found to have deep (> 50%) myometrial invasion (P= 0.008).

RESULTS

With a median follow‐up time of 48 months, the 5‐year locoregional control (LRC), disease‐free survival (DFS), and overall survival (OS) rates were 95%, 91%, and 90% respectively. On multivariate analysis, poor LRC was found to be correlated with age ≥ 70 years (P= 0.019) and lymphovascular invasion (P= 0.001). Poor DFS was found to be correlated with age ≥ 70 years (P= 0.03), lymphovascular invasion (P= 0.01), and aggressive histology (P= 0.001). Similarly, poor OS was found to correlate with age ≥ 70 years (P= 0.001), lymphovascular invasion (P= 0.01), aggressive histology (P= 0.01), and cervical involvement (P= 0.02). The same factors that were found to correlate with OS (age ≥ 70 years, lymphovascular involvement, aggressive histology, and cervical involvement) also appeared to correlate with disease‐specific survival (P= 0.03,P= 0.008,P= 0.001, andP= 0.04, respectively). The 5‐year actuarial rates of Radiation Therapy Oncology Group late complications that were ≥ Grade 3 (gastrointestinal tract, genitourinary tract, or vagina) were 3% in both groups.

CONCLUSIONS

Even when treated in a similar fashion, endometrial carcinoma patients age ≥ 70 years appear to fare worse than younger patients independent of other poor prognostic factors. The rate of complications from adjuvant RT, despite a higher rate of comorbidity in elderly patients, was found to be similar in both age groups. Endometrial carcinoma appears to be intrinsically more aggressive in older patients, thus mandating further improvement in their treatment strategies. Cancer 2003. © 2003 American Cancer Society.
A linearized implicit pseudo‐spectral method for some model equations: the regularized long wave equations
Authors: Djidjeli K. , Price W. G. , Twizell E. H. , Cao Q.
Published: November 2003

An efficient numerical method is developed for the numerical solution of non‐linear wave equations typified by the regularized long wave equation (RLW) and its generalization (GRLW). The method developed uses a pseudo‐spectral (Fourier transform) treatment of the space dependence together with a linearized implicit scheme in time. =10pt An important advantage to be gained from the use of this method, is the ability to vary the mesh length, thereby reducing the computational time. Using a linearized stability analysis, it is shown that the proposed method is unconditionally stable. The method is second order in time and all‐order in space. The method presented here is for the RLW equation and its generalized form, but it can be implemented to a broad class of non‐linear long wave equations (Equation (2)), with obvious changes in the various formulae. Test problems, including the simulation of a single soliton and interaction of solitary waves, are used to validate the method, which is found to be accurate and efficient. The three invariants of the motion are evaluated to determine the conservation properties of the algorithm. Copyright © 2003 John Wiley & Sons, Ltd.
Can the principle of the ecological footprint be applied to measure the environmental sustainability of business?
Authors: Holland Leigh
Published: November 2003

Ecological footprinting is an accounting tool that seeks to quantify the biological capacity that is required to support human activity. It has been used at the city or country level, but as yet it has not been applied at the lowest level of economic activity – the business enterprise. In order to assess its usefulness the technique is reviewed alongside other management tools for assessing the environmental performance of commercial organizations. This will then enable the business to develop environmental management systems and strategies to improve environmental performance and eco‐efficiency. Copyright © 2003 John Wiley & Sons, Ltd and ERP Environment.
Optimizing the QoS of high speed moving terminals in cellular networks
Authors: Ioannou K. , Kotsopoulos S. , Stavroulakis P.
Published: November 2003

This paper presents a dynamic guard channel assignment technique based on a two‐layer cellular architecture which optimizes the blocking probability performance of high‐speed moving terminals (HSMT) and handoff calls of low‐speed moving terminals (LSMT), in a congested urban area. The lower layer of the proposed architecture is based on a microcellular solution, for absorbing the traffic loads of LSMT. The higher layer is based on a macro‐cell umbrella solution, for absorbing the traffic load of the HSMT. The results show that using the optimum number of channels and adjusting dynamically the number of guard channels in each layer, the blocking probability of the HSMT and the handoff blocking probability of LSMT is optimized having the minimum bad effect on the new call blocking probability of LSMT. Copyright © 2003 John Wiley & Sons, Ltd.
Differential role of IL‐18 and IL‐12 in the host defense against disseminated Candida albicans infection
Authors: Netea Mihai G. , Vonk Alieke G. , van den Hoven Mabel , Verschueren Ineke , Joosten Leo A. , van Krieken Johan H. , van den Berg Wim B. , Van der Meer Jos W. M. , Kullberg Bart Jan
Published: November 2003

IFN‐γ plays a crucial role in the defense against infection with Candida albicans. Since IL‐18 and IL‐12 are strong stimuli of IFN‐γ production, we investigated whether endogenous IL‐18 and IL‐12 are involved in the host defense during disseminated candidiasis. IL‐18 knockout (IL‐18‐/‐) mice, but not IL‐12‐/‐ mice, displayed an increased mortality due to C. albicans infection, accompanied by a decreased clearance of the yeasts from the kidneys late during the course of infection. Histopathology of the organs, combined with phagocyte recruitment experiments, showed a decreased influx of monocytes at the sites of Candida infection, mainly in the IL‐18‐/‐ mice. Whereas production of the chemokine KC was decreased in both IL‐18‐/‐ and IL‐12‐/‐ mice, MIP‐2 production was deficient only in IL‐18‐/‐ animals, which may explain the differences in phagocyte recruitment. In addition, although IFN‐γ production capacity, as a parameter of the Th1‐protective immunity, was reduced by 65 to 80% in the IL‐12‐/‐ mice, this defect was even more pronounced in the IL‐18‐/‐ mice (85 to 95% downmodulation). In conclusion, the anticandidal effects of endogenous IL‐18 are mediated late during the infection by assuring a proper IFN‐γ response and promoting the infiltration of the site of infection by monocytes.
O‐Linked glycans control glycoprotein processing by antigen‐presenting cells: a biochemical approach to the molecular aspects of MUC1 processing by dendritic cells
Authors: Hanisch Franz‐Georg , Schwientek Tilo , Von Bergwelt‐Baildon Michael S. , Schultze Joachim L. , Finn Olivera
Published: November 2003

MUC1 is a glycoprotein overexpressed in breast cancer and other adenocarcinomas, and is known to elicit cellular and humoral immunity directed against unglycosylated peptide epitopes in the repeat domain. Based on immunological evidence that O‐linked glycans on repeat peptides remain intact during processing by dendritic cells (DC), we used MUC1 as a model to address the question which role O‐linked glycans play in this process. We were able to identify the sites of proteolysis in MUC1 repeats and the enzyme(s) involved, and elucidated the site‐specific effects of O‐glycosylation on MUC1 processing by human and mouse DC. Peptides generated by the cellular processing machinery from native mucin or (glyco)peptides suggest specific cleavage at Gly13‐Ser14, His20‐Gly1 and Thr3‐Ser4 peptide bonds in the tandem repeat GVTSAPDTRPAPGSTAPPAH resulting in the initial formation of STA27 or GVT20 and SAP17 as the final product with intact O‐glycosylation. Human cathepsin L and the corresponding mouse enzyme in low‐density endosomes were identified in vitro to catalyze this site‐specific MUC1 proteolysis. O‐Glycosylation controls the processing by preventing proteolysis of the Thr3‐Ser4 peptide bond if either amino acid is glycosylated, and is responsible for the inertness of tumor‐associated MUC1 glycoforms to effective DC processing by masking this cleavage site.
Regulation of peptide presentation by major histocompatibility complex class II molecules at the surface of macrophages
Authors: von Delwig Alexei , Musson Julie A. , McKie Norman , Gray Joe , Robinson John H.
Published: November 2003

We studied major histocompatibility complex class II‐dependent presentation of two T cell epitopes delivered as synthetic peptides by fixed macrophages. Treatment of bone marrow macrophages with inhibitors of proteinases of the metallo‐, aspartic and serine proteinase families enhanced presentation of peptides, indicating that several enzyme families participate in destructive antigen processing of exogenous peptides. High performance liquid chromatography and mass spectrometry analysis demonstrated the presence of peptide fragments in macrophage supernatants, and permitted identification of the cleavage sites which confirmed the enzyme families involved. Peptide fragments were shown to be competitive inhibitors of presentation of the full‐length peptide to CD4 T cells by fixed and live macrophages. The results indicate that several classes of proteinases can modulate antigen presentation by at least two mechanisms: (1) degradation of extracellular oligopeptides and (2) generation of natural peptide ligands that block antigen presentation to CD4 T cells. The generation of inhibitory natural peptide ligands is a new mechanism of immunoregulation which could operate during the induction of T cell responses in a variety of situations.
Comparative analysis of NK‐ or NK‐CTL‐mediated lysis of immature or mature autologous dendritic cells
Authors: Pietra Gabriella , Romagnani Chiara , Mazzarino Paola , Millo Enrico , Moretta Lorenzo , Mingari Maria Cristina
Published: November 2003

Natural killer (NK) cells have been shown to kill efficiently autologous immature dendritic cells (iDC), while sparing those undergone maturation. In this study we investigated the effect of the interaction between autologous DC and NK‐cytolytic T lymphocytes (NK‐CTL), a subset of HLA‐E‐restricted CD8+ T cells that express HLA class I‐specific inhibitory NK receptors. Although these cells share with NK cells various phenotypic and functional features (such as the capacity to lyse most allogeneic, NK‐susceptible tumor cell lines), different from NK cells, NK‐CTL failed to lyse autologous DC. However, after pulsing DC with a cytomegalovirus‐derived, HLA‐E‐binding peptide recognized by NK‐CTL, both iDC and mature DC became highly susceptible to lysis. On the other hand,the addition of the peptide resulted in the down‐regulation of the NK‐mediated lysis of the same autologous iDC. The capability of killing autologous DC, presenting a non‐self, HLA‐E‐binding peptide, may represent a feedback mechanism by which NK‐CTL down‐regulate HLA‐E‐restricted responses to certain pathogens.
Contrasting roles of DAP10 and KARAP/DAP12 signaling adaptors in activation of the RBL‐2H3 leukemic mast cell line
Authors: Anfossi Nicolas , Lucas Mathias , Diefenbach Andreas , Bühring Hans‐Jörg , Raulet David , Tomasello Elena , Vivier Eric
Published: November 2003

A common feature of hematopoietic activating immunoreceptors resides in their association at the cell surface with transmembrane signaling adaptors. Several adaptors, such as the CD3 molecules, FcRγ and KARAP/DAP12, harbor intracytoplasmic immunoreceptor tyrosine‐based activation motifs (ITAM) that activate Syk‐family protein tyrosine kinases. In contrast, another transmembrane adaptor, DAP10, bears a YxxM motif that delivers signals by activation of lipid kinase pathways. We show here that the human signal‐regulatory protein SIRPβ1 can associate with both DAP10 and KARAP/DAP12 in a model of RBL‐2H3 cell transfectants. In association with KARAP/DAP12, SIRPβ1 complexes are capable of inducing serotonin release and tumor necrosis factor (TNF) secretion. By contrast,in the absence of KARAP/DAP12, engagement of SIRPβ1:DAP10 complexes does not lead to detectable serotonin release or TNF secretion by RBL‐2H3 transfectants. However, triggering of SIRPβ1:DAP10 complexes co‐stimulates RBL‐2H3 effector function induced by sub‐optimal stimulation of the endogenous FcϵRI complex. Therefore, we report here a cellular model in which the association of a cell surface receptor with various signaling adaptors dictates the co‐stimulatory or the direct stimulatory properties of the complex.
Efficient Synthesis of Doubly Connected Primary Face‐to‐Face Cyclodextrin Homo‐Dimers
Authors: Lecourt Thomas , Mallet Jean‐Maurice , Sinaÿ Pierre
Published: November 2003

“Head‐to‐head” type α‐ and β‐cyclodextrin homo‐dimers in which the two primary rims are doubly ligated through alkyl chains have been synthesised in high yield by acyclic diene metathesis (ADM), followed by ring‐closing metathesis (RCM). (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Buttressing Effects Rerouting the Deprotonation and Functionalization of 1,3‐Dichloro‐ and 1,3‐Dibromobenzene
Authors: Heiss Christophe , Marzi Elena , Schlosser Manfred
Published: November 2003

A systematic comparison between 1,3‐difluorobenzene, 1,3‐dichlorobenzene, and 1,3‐dibromobenzene did not reveal major differences in their behavior towards strong bases such as lithium diisopropylamide or lithium 2,2,6,6‐tetramethylpiperidide. Thus, all 2,6‐dihalobenzoic acids 1 are directly accessible by consecutive treatment with a suitable base and dry ice. In contrast, (2,6‐dichlorophenyl)‐ and (2,6‐bromophenyl)triethylsilane (2a and 2b) were found to undergo deprotonation at the 5‐position (affording acids 3 and, after deprotection, 4), whereas the 1,3‐difluoro analog is known to react at the 4‐position. The 2,4‐dihalobenzoic acids 7 were selectively prepared from either the silanes 2 (by bromination at the 4‐position, metalation and carboxylation of the neighboring position, followed by desilylation and debromination) or the 1,3‐dihalo‐2‐iodobenzenes 8 (by base‐promoted migration of iodine to the 4‐position followed by iodine/magnesium permutation and subsequent carboxylation). (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)