bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractGramicidin 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

AbstractPeptide‐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

AbstractMechanical 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

AbstractThe 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

AbstractWe 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

AbstractTo 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

AbstractThe 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

AbstractAn 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

AbstractClassical 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

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

AbstractBACKGROUNDCancer 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.METHODSThe 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.RESULTSOf 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.CONCLUSIONSThe 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

AbstractBACKGROUNDThe 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.METHODSA 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).RESULTSTwenty‐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.CONCLUSIONSPatients 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

AbstractBACKGROUNDAlthough < 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.METHODSThe 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.RESULTSSeventeen 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.CONCLUSIONSThe 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.