bluuebunny/crossref_metadata_2025 huggingface dataset:
A hybrid approach combining energy density analysis with the interaction energy decomposition method
Authors: Kawamura Yoshiumi , Nakai Hiromi
Published: September 2004

We propose a new analysis technique for characterizing molecular interactions that combines an energy decomposition scheme, such as the Kitaura–Morokuma decomposition method, with energy density analysis, which partitions the total energy of the system into atomic contributions. The combined scheme, termed Interaction‐EDA, enables us to estimate the local contribution of interaction energy components, such as electrostatic, exchange, polarization, and charge transfer. The evaluation of the local interaction energy is rather important in large systems. For a numerical assessment, the Interaction‐EDA method is applied to the process of CO adsorption on Si(100) − (2 × 1) surface. © 2004 Wiley Periodicals, Inc. J Comput Chem 25: 1882–1887, 2004
Calculation of the vibration frequencies of α‐quartz: The effect of Hamiltonian and basis set
Authors: Zicovich‐Wilson C. M. , Pascale F. , Roetti C. , Saunders V. R. , Orlando R. , Dovesi R.
Published: September 2004

The central‐zone vibrational spectrum of α‐quartz (SiO2) is calculated by building the Hessian matrix numerically from the analytical gradients of the energy with respect to the atomic coordinates. The nonanalytical part is obtained with a finite field supercell approach for the high‐frequency dielectric constant and a Wannier function scheme for the evaluation of Born charges. The results obtained with four different Hamiltonians, namely Hartree–Fock, DFT in its local (LDA) and nonlocal gradient corrected (PBE) approximation, and hybrid B3LYP, are discussed, showing that B3LYP performs far better than LDA and PBE, which in turn provide better results than HF, as the mean absolute difference from experimental frequencies is 6, 18, 21, and 44 cm−1, respectively, when a split valence basis set containing two sets of polarization functions is used. For the LDA results, comparison is possible with previous calculations based on the Density Functional Perturbation Theory and usage of a plane‐wave basis set. The effects associated with the use of basis sets of increasing size are also investigated. It turns out that a split valence plus a single set of d polarization functions provides frequencies that differ from the ones obtained with a double set of d functions and a set of f functions on all atoms by on average less than 5 cm−1. © 2004 Wiley Periodicals, Inc. J Comput Chem 25: 1873–1881, 2004
The psychology of thinking, animal psychology, and the young Karl Popper
Authors: ter Hark Michel
Published: September 2004

In the 1920s, Karl Popper wrote two large manuscripts on psychology that he never published. In his autobiography, Unended Quest, he attempts to reduce the importance of his work in psychology as much as possible, and in his philosophical work he is an antipsychologist. However, in this article, it is argued that Popper's early psychology has been pivotally important for the development of his philosophy. In particular, it is shown that Popper's views on psychology underwent a radical shift, one that paved the way for his characteristic deductive stance in philosophy. Popper's views shifted from an inductive and associationistic psychology toward a noninductive psychology of problem solving. Tracing the historical background of Popper's early work reveals how he integrated various parts of the psychology of Karl Groos into his analysis of the childish phenomenon of dogmatic thinking and how he shortly after appropriated various elements of the animal psychology of Hans Volkelt and Herbert Jennings in his biological approach to (dogmatic) thinking. In the monumental works of Otto Selz, however, Popper finally found the roots of a noninductive and biological approach to the growth of individual and scientific knowledge. © 2004 Wiley Periodicals, Inc.
Mental tests and fossils
Authors: Littman Richard A.
Published: September 2004

This article investigates the origins of the intelligence test item known as the Ball and Field in Lewis M. Terman's Stanford Revision of the Binet‐Simon Intelligence Scale. The question was initially raised by the resemblance of paleontological ocean bed floor tracings left by ancient creatures to the responses produced by children given the Ball and Field Test. A version of the Ball and Field Test was invented by Clifton F. Hodge, one of Terman's graduate school instructors who devised it as a result of his observations about how birds and other animals navigated and found their way. He then tested how humans and children located hidden objects and found that, in many ways, animals and humans used similar strategies for getting home or finding objects. © 2004 Wiley Periodicals, Inc.
A kit formulation for the labelling of lipiodol with generator‐produced 188Re
Authors: Lepareur Nicolas , Garin Etienne , Noiret Nicolas , Herry J. Y.
Published: September 2004

A lyophilised kit formulation for the efficient labelling of lipiodol with generator‐produced 188Re is described. This method involves the reaction of [188ReVIIO4]− (37–370 MBq) with SnCl2 as a reducing agent, potassium oxalate as a reduction promoter, ascorbic acid as antioxidant and sodium gluconate as a weak chelate. The intermediate compound Na[188ReVO(gluc)2] reacts with the sodium salt of a dithiobenzoate ligand to give the neutral complex [188ReIII(PhCS3)2(PhCS2)]. This complex is then quantitatively extracted with lipiodol to afford a stable solution. Radiochemical purity (RCP) was greater than 90% and the yield of extraction was about 88%. The role of the different kit components has been studied in detail to find the most efficient formulation (amount of reducing agent, antioxidant). The use of 0.8 mg of stannous chloride, with 40 mg of potassium oxalate and 30 mg of ascorbic acid, was found necessary. The stability of the 188Re‐radiolabelled lipiodol has been investigated, in the presence of plasma. The radiolabelled lipiodol (188Re‐SSS lipiodol) is stable at least 48 h (RCP=91.0±4.0%). Copyright © 2004 John Wiley & Sons, Ltd.
Isotope labeled ‘HEA Moiety’ in the synthesis of labeled HIV‐protease inhibitors – Part 1
Authors: Ekhato I. Victor , Liao Yuan , Plesescu Mihaela
Published: September 2004

[(S)‐1′‐((N‐tert‐Butyloxycarbonyl)amino)‐2S‐[2H5]phenyl‐ethyl]oxirane 11, made from [2H5]‐bromobenzene, was transformed into the HIV‐protease inhibitors [2H5]‐DPH 153893 and [2H5]‐DPH 140662. Both compounds are members of the hydroxyethylamine class of protease inhibitors (HIV‐PIs). The method of synthesis is applicable to members of this class and the HEE group of HIV‐PIs. Copyright © 2004 John Wiley & Sons, Ltd.
The syntheses of [14C] and [13C2,15N3]aprepitant
Authors: Elmore Charles S. , Dean Dennis C. , Zhang Yong , Mellilo David G.
Published: September 2004

In support of a program to develop a treatment for chemotherapy‐induced nausea and vomiting, two isotopically labeled forms of neurokinin‐1 receptor antagonist aprepitant have been synthesized. A [l4C]‐labeled version was synthesized for use in metabolism studies, while a [13C2,15N3]‐labeled version was synthesized for use in a study to determine the bioavailability of the final market image. Both syntheses utilized labeled chloroacetonitrile which was synthesized in two steps from labeled potassium cyanide. Copyright © 2004 John Wiley & Sons, Ltd.
Synthesis of deuterium, tritium, and carbon‐14 labeled BIRB 796, a p38 MAP kinase inhibitor
Authors: Latli Bachir
Published: September 2004

1‐(5‐tert‐Butyl‐2‐p‐tolyl‐2H‐pyrazol‐3‐yl)‐3‐[4‐(2‐morpholin‐4‐yl‐ethoxy)naphthalen‐1‐yl]urea (BIRB 796), currently in clinical trials for the treatment of inflammatory diseases, is a potent inhibitor of p38 MAP kinase. Labeled BIRB 796 with stable and radioactive isotopes was required for metabolism, distribution, and absorption studies. We first report the synthesis of carbon‐14 labeled BIRB 796 with a specific activity of 2 GBq/mmol (54.2 mCi/mmol), using [14C]‐phosgene under modified Schotten–Baumann conditions; second the preparation of tritium‐labeled BIRB 796 with a specific activity of 659 GBq/mmol (17.81 Ci/mmol) by reductive dehalogenation of iodo‐BIRB 796 with tritium gas; and finally, the synthesis of 2H8‐BIRB 796 using morpholine‐2,2,3,3,5,5,6,6‐2H8 with isotopic enrichment of 98.9 at% 2H. Copyright © 2004 John Wiley & Sons, Ltd.
Synthesis of [13C7]3,5‐dichlorobenzylamine hydrochloride
Authors: Harwood Simon J.
Published: September 2004

Commercially available [13C6]aniline (2) was readily converted into [13C6]1‐bromo‐3,5‐dichlorobenzene (5). A further stable label was introduced by cyanation of aryl bromide (5), using K13CN and cuprous iodide. Borane reduction of benzonitrile (6), followed by an acid work up, furnished [13C7]3,5‐dichlorobenzylamine hydrochloride (1), which was further elaborated to provide an internal standard for use in LC‐MS assays. Copyright © 2004 John Wiley & Sons, Ltd.
Collision courses: When social identity leads to conflict
Authors: Ohlott Patricia J. , Chrobot‐Mason Donna , Dalton Maxine A.
Published: September 2004

As people with far different social identities increasingly find themselves working together, clashes, differences of opinion, and even serious conflicts are bound to occur. These can have acute consequences for organizations. The challenge for leaders is to effectively manage and resolve such conflicts or, better yet, anticipate and prevent them from happening at all.
Luminescent Monomer and Poly(methacrylate) Containing 1,3,4‐Oxadiazole and Stilbene Units: Synthesis and Optical Properties
Authors: Mikroyannidis John A.
Published: September 2004

Summary: A monomer M as well as a poly(methacrylate) P carrying the same chromophore, that consists of 1,3,4‐oxadiazole and stilbene units, were efficiently synthesized. They dissolved in common organic solvents such as THF, chloroform, dichloromethane, 1,1,2,2‐tetrachloroethane and chlorobenzene. P showed a Tg value of 145 °C. Both M and P were stable up to approximately 300 °C and afforded anaerobic char yield of about 40% at 800 °C. Their optical properties were comparable. They emitted intense violet‐blue light in THF solution with a PL maximum at 413 nm and a PL quantum yield of 0.29 for M and 0.73 for P. Thin films of them displayed optical band gap of 3.03 eV and blue‐light emission with a PL maximum around 440 nm. The PL curves of both samples were progressively red‐shifted with increasing the solvent polarity. The influence of the annealing on the PL emission spectrum of M and P thin films was investigated.

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Measurement of in situ Monomer Sorption in Poly(propylene)
Authors: Pater Jochem T. M. , Weickert Günter , Fait Anna , Mei Gabriele
Published: September 2004

Summary: An experimental method has been developed to compare the amount of monomer absorbed in freshly produced poly(propylene) with the amount of monomer absorbed in the same material after degassing. It has been found that propylene sorption in freshly produced poly(propylene) is significantly higher than the sorption in the same but degassed polymer. The difference depends on the degree of drying and is time‐dependent. This fact can be an explanation for reduced activity often observed in the transition from liquid‐ to gas‐phase polymerization.

Pressure profile during the pressure‐swing part of the experiment.

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Pressure profile during the pressure‐swing part of the experiment.
Ischemia/reperfusion injury: A review in relation to free tissue transfers
Authors: Siemionow Maria , Arslan Emrah
Published: September 2004

Events during ischemia/reperfusion (I/R) injury include: neutrophil‐mediated endothelial cytotoxicity and activation, generation of free radicals, triggering of cytokines and chemokines, and activation of adhesion molecules and complement system. This article briefly reviews events occurring during tissue ischemia and reperfusion in relation to free tissue transfers. The consequences of tissue damage at the microcirculatory level are presented. Preventive measures of I/R injury are outlined. © 2004 Wiley‐Liss, Inc. Microsurgery 24:468–475, 2004.
Use of muscle‐vein‐combined Y‐chambers for repair of multiple nerve lesions: Experimental results
Authors: Tos Pierluigi , Calcagni Maurizio , Gigo‐Benato Davilene , Boux Elena , Geuna Stefano , Battiston Bruno
Published: September 2004

Y‐shaped vein conduits enriched with fresh skeletal muscle fibers were used to bridge a concomitant ulnar and median nerve transection with substance loss in rats. The proximal limb of the Y‐chamber was sutured to the proximal ulnar nerve, while the two distal limbs were sutured to ulnar and median distal nerve stumps. Eight months after surgery, median nerve functional recovery was evaluated by means of the grasping test, and nerve fiber regeneration in both repaired nerves was assessed by means of design‐based histomorphometry. Results showed that nerve fibers regenerated along both severed nerve trunks, and in the median nerve led to a recovery corresponding to 58% of normal nerve function. Quantitative analysis showed no significant morphological differences between myelinated nerve fibers regenerated along the two distal nerves except for the number of fibers, which was higher in the median nerve. Notably, the total number of regenerated nerve fibers in the two distal nerves was 4‐fold the normal fiber number in the ulnar nerve. Besides their interest in relation to the long‐lasting debate about the topographic specificity of nerve regeneration, the results of this study show an effective way to repair, in the rat experimental model, two transected nerve trunks innervating agonistic muscles in the case that the proximal stump of only one nerve is preserved. © 2004 Wiley‐Liss, Inc. Microsurgery 24:459–464 2004.
Technique for retransplanting heterotopic heart grafts in mice
Authors: Li Qi , Wang Yinong , Yi Tai , Chalasani Geetha , Dai Zhenhua , Lorber Marc I. , Tellides George , Lakkis Fadi G.
Published: September 2004

Removal of a transplanted organ from its original recipient and retransplanting it into a new host is an important method to study the role of the graft in the rejection process. Here we describe a novel technique of heart retransplantation in the mouse. In this technique, a primarily vascularized heart graft is anastomosed to the abdominal aorta and inferior vena cava of a syngeneic or immunodeficient allogeneic mouse, using standard techniques. Either 10 or 70 days later, the same graft is retransplanted into the abdomen of a second mouse by end‐to‐side anastomosis of the donor (first recipient) aortic and inferior vena cava's cuffs to the second recipient's abdominal aorta and inferior vena cava, respectively. A greater than 90% success rate was achieved by using this microsurgical technique. This method should be useful for studying intragraft factors, such as ischemia‐reperfusion injury and donor antigen‐presenting cells, on the outcomes of transplantations. © 2004 Wiley‐Liss, Inc. Microsurgery 24:465–467, 2004.
Reconstruction of large posttraumatic skeletal defects of the forearm by vascularized free fibular graft
Authors: Adani Roberto , Delcroix Luca , Innocenti Marco , Marcoccio Ignazio , Tarallo Luigi , Celli Andrea , Ceruso Massimo
Published: September 2004

Vascularized bone graft is most commonly applied for reconstruction of the lower extremity; indications for its use in the reconstruction of the upper extremity have expanded in recent years. Between 1993–2000, 12 patients with segmental bone defects following forearm trauma were managed with vascularized fibular grafts: 6 males and 6 females, aged 39 years on average (range, 16–65 years). The reconstructed site was the radius in 8 patients and the ulna in 4. The length of bone defect ranged from 6–13 cm. In 4 cases, the fibular graft was harvested and used as a vascularized fibula osteoseptocutaneous flap. To achieve fixation of the grafted fibula, plates were used in 10 cases, and screws and Kirschner wires in 2. In the latter 2 cases, an external skeletal fixator was applied to ensure immobilization of the extremity. The follow‐up period ranged from 10–93 months. Eleven grafts were successful. The mean period to obtain radiographic bone union was 4.8 months (range, 2.5–8 months). Fibular grafts allow the use of a segment of diaphyseal bone which is structurally similar to the radius and ulna and of sufficient length to reconstruct most skeletal defects of the forearm. The vascularized fibular graft is indicated in patients with intractable nonunions where conventional bone grafting has failed or large bone defects, exceeding 6 cm, are observed in the radius or ulna. © 2004 Wiley‐Liss, Inc. Microsurgery 24:423–429, 2004.
Modified distally based peroneal artery perforator flap for reconstruction of foot and ankle
Authors: Chang Shi‐Min , Zhang Feng , Yu Guang‐Rong , Hou Chun‐Lin , Gu Yu‐Dong
Published: September 2004

The distally based sural fasciocutaneous flap has been used widely for reconstruction of foot and ankle soft‐tissue defects. Here we report on a series of cases of foot and ankle reconstruction with a modified distally based sural flap. The vascular pedicle of the flap includes an axial perforator branch of the peroneal artery and two concomitant veins. This modified distally based perforator flap, measuring around 17 × 6 cm to 30 × 10 cm in size, was transferred for coverage of foot and ankle soft‐tissue defects in 7 cases. All flaps survived completely. Neither arterial ischemia nor venous congestion was noted. As compared to other distally based sural flaps with neuro‐veno‐adipo‐fascial pedicles, this modified sural flap with a thin perforator pedicle is easily rotated. The flap can obtain abundant blood supply through both axial perforator and longitudinal chain‐linked vascular plexuses, and does not have the venous reflow problem. In conclusion, the invention of this perforator fasciocutaneous flap provides a valuable tool for repair of foot and ankle soft‐tissue defects. © 2004 Wiley‐Liss, Inc. Microsurgery 24:430–436, 2004.
Effects of high pressure on Friedel–Crafts benzoylation
Authors: Mugnier Florence , Harrison‐Marchand Anne , Igersheim Françoise , Maddaluno Jacques
Published: September 2004

A study of Friedel‐Crafts benzoylation under high pressure is reported. Activated (toluene) to non‐activated (benzene) and deactivated (fluorobenzene) aromatic substrates were acylated (benzoyl chloride) at 34 °C for 3 h 50 min in the presence of the usual Lewis acid AlCl3, raising the pressure from atmospheric pressure (1 bar) to 10 kbar. Non‐activated and deactivated aromatic substrates were found to be more sensitive to the effect of the high pressure. Indeed, fluorobenzene led to the expected aromatic ketone with a 56% yield under the conditions mentioned above (5 kbar), whereas the yields constantly decreased for toluene when the pressure increased. Hyperbaric activation has the advantage of being able to conduct such a transformation on deactivated substrates, avoiding very acidic catalysts such as trifluoromethanesulfonic acid or expensive activators such as gallium nonaflate. Copyright © 2004 John Wiley & Sons, Ltd.
Assessment of the metabolic stability of the methyl groups in heterocyclic compounds using CH bond dissociation energies: Effects of diverse aromatic groups on the stability of methyl radicals
Authors: Zhao Su‐Wen , Liu Lei , Fu Yao , Guo Qing‐Xiang
Published: September 2004

The CH bond dissociation energies (BDEs) of the methyl groups attached to a large number of heterocyclic compounds are calculated using a carefully calibrated B3LYP method. These CH bond dissociation energies are important for evaluating the metabolic stability of the methyl groups in heterocyclic compounds that may be used as drug candidates. It is found that the CH BDEs of the methyl groups attached to diverse heterocycles can dramatically vary from ca 80 to ca 100 kcal mol−1 (1 kcal = 4.184 kJ). Therefore, the benzylic positions of different heterocycles may have remarkably different metabolic stabilities varying by ∼1012‐fold. The heteroatoms in the aromatic rings vary the benzylic BDEs either by delocalizing the spin or by changing the charge carried by the radical center. N‐Methyl groups have systematically higher CH BDEs than C‐methyl groups. NH, O and S groups have similar effects on the benzylic CH BDEs. A methyl group at the α‐position relative to the NH, O and S groups usually has a lower BDE than that at the β‐position. On the other hand, the N group has a different effect on the benzylic CH BDEs. A methyl group at the β‐position relative to N has a lower CH BDE than that at the α‐position. There is a special aromatization effect associated with 1‐methyl‐2H‐isoindole, 1‐methylisobenzofuran, 1‐methylbenzo[c]thiophene and related compounds. This aromatization effect dramatically decreases the benzylic CH BDEs. Finally, an interesting QSAR model has been developed. This model not only can successfully predict the benzylic CH BDEs of diverse heterocyclic compounds, but also can clearly and quantitatively reveal the mechanisms for the variation of the CH BDEs. Copyright © 2004 John Wiley & Sons, Ltd.
Relationship between calculated core‐electron binding energy shifts and Hammett substituent (sigma) constants: I
Authors: Takahata Yuji
Published: September 2004

For monosubstituted benzenes (Ph‐Z), Linderberg et al. demonstrated the validity of the equation ΔCEBE ≈ κσ, where ΔCEBE is the difference between the core‐electron binding energies (CEBE) of a specific carbon in monosubstituted benzene derivatives (Ph‐Z) and that of unsubstituted benzene (Ph‐H), κ is related to the reaction constant and σ is the experimental Hammett sigma constant. CEBEs of carbon atoms for a series of Ph‐Z were calculated using density functional theory (DFT) with the scheme ΔEKS(PW86‐PW91)/TZP+Crel//HF/6‐31G*. An average absolute deviation of 0.15 eV was obtained with respect to observed values. A linear regression analysis of the form Y = A+BX of a plot of, for instance, Hammett σp‐constants against calculated ΔCEBEs (in eV) at para‐carbon for n = 11 produced a value of A = −0.1310 and B = 1.056 with a correlation coefficient R = 0.983, a standard deviation of 0.099 and a p‐value  < 0.0001. Copyright © 2004 John Wiley & Sons, Ltd.
Molecular targets of doxazosin in human prostatic stromal cells
Authors: Zhao Hongjuan , Lai Frank , Nonn Larisa , Brooks James D. , Peehl Donna M.
Published: September 2004

BACKGROUND

We used cDNA microarray analysis to obtain insights into the mechanisms of action of doxazosin, an α1‐adrenergic receptor antagonist used to treat benign prostatic hyperplasia (BPH).

METHODS

Hierarchical clustering analysis and significance analysis of microarray (SAM) were performed to identify genes differentially expressed between untreated stromal cells cultured from normal tissue and BPH, and changes in gene expression induced by doxazosin. Transcript levels of selected genes were validated by real‐time reverse‐transcription polymerase chain reaction (RT‐PCR).

RESULTS

Hierarchical clustering analyses separated untreated normal and BPH cells. Sixty‐seven genes whose expression varied at least twofold after doxazosin treatment in both normal and BPH cells were identified, as were 93 genes differentially regulated in normal versus BPH cells. Molecular targets consistent with tumor necrosis factor (TNF)‐α‐related activity were identified.

CONCLUSIONS

Normal versus BPH stromal cells differ in global gene transcription. Doxazosin induced gene expression changes relevant to proliferation/apoptosis, immune defense, cell–cell signaling/signal transduction, and transcriptional regulation. © 2004 Wiley‐Liss, Inc.
Ambiguities in the calculation of dislocation self energies
Authors: LeSar R.
Published: September 2004

Various forms for the interactions between dislocations have been given in the literature. While arising from the same basic expression, they differ in terms that vanish when integrating over an entire dis‐location loop and thus yield the same value for the interaction energy between distinct dislocations. In this paper, however, we show that when applied to dislocation self energies, which because of a core cutoff do not involve integrations over the entire loop, these expressions may not yield equivalent results. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
11th International Conference on High‐Pressure Semiconductor Physics (HPSP‐11), Berkeley, USA, 2–5 August 2004
Authors: Cardona M.
Published: September 2004

Conference Reports are meant to offer an authoritative view on a recently held scientific meeting rather than a comprehensive list of the conference presentations. Authors are invited to describe what they feel were the most interesting contributions.

The Proceedings of the 11th International Conference on High‐Pressure Semiconductor Physics (HPSP‐11) will be published in phys. stat. sol. (b) in November 2004.
Quantitative evaluation of the atomic structure of defects and composition fluctuations at the nanometer scale inside InGaN/GaN heterostructures
Authors: Ruterana P. , Singh P. , Kret S. , Jurczak G. , Maciejewski G. , Dluzewski P. , Cho H. K. , Choi R. J. , Lee H. J. , Suh E. K.
Published: September 2004

The cover picture of this issue depicts indium composition fluctuations in InGaN/GaN multi quantum wells. The coded color strain distribution (left) was derived from finite element method calculations of the strain relaxation process and high‐resolution transmission electron microscopy (HRTEM) image simulations, superimposed on the HRTEM image of the quantum wells. The possible corresponding shape and εxx strain profiles in the indium rich clusters (right) hint at a concentration close to pure InN in their core. The paper by Pierre Ruterana et al. [1] was presented at the 5th International Symposium on Blue Laser and Light Emitting Diodes (ISBLLED‐2004), held in Gyeongju, Korea, 15–19 March 2004.

Further papers from ISBLLED‐2004 are published in phys. stat. sol. (a) 201, No. 12 (2004) and phys. stat. sol. (c) 1, No. 10 (2004).
Synthesis, Screening and Evaluation of a Combined Library of Tweezer‐ and Tripodal Synthetic Receptors
Authors: Monnee Menno C. F. , Brouwer Arwin J. , Liskamp Rob M. J.
Published: September 2004

The split‐mix synthesis of a 6912‐member combined library of tweezer‐ and tripodal synthetic receptors is described. This library was prepared by solid phase attachment of a tweezer hinge, a “locked” tweezer hinge and two triazacyclophane (“TAC”) tripodal scaffold, followed by three split‐mix cycles using twelve α‐amino acid (Gly, Ala, Val, Leu, Pro, Phe, Tyr, Lys, Ser, Asp, Gln, His) derivatives. Using fluorescence microscopy and image analysis, the resulting library was screened in aqueous phosphate buffer with fluorescent fragments of the cell wall of Gram‐positive Staphylococcus aureus i.e. Ds‐Gly‐D‐Ala‐D‐Ala‐OH and Ds‐Gly‐D‐Ala‐D‐Lac‐OH as well as FITC‐labeled peptidoglycan fragments. Decoding of selected beads by Edman degradation gave the structures of the possible synthetic receptors, of which thirteen were resynthesized on the solid phase, including one using a cleavable linker containing resin for confirmation of the quality of the resynthesized receptor. Remarkable binding selectivities were observed, for example the presence of Lys (AA3) in almost half of the sequenced receptors arms binding to Ds‐Gly‐D‐Ala‐D‐Ala‐OH, which is less the case in the receptors binding Ds‐Gly‐D‐Ala‐D‐Lac‐OH. Especially prominent was the presence of a Pro residue as AA3 in more than half of the arms of the sequenced receptors. The observed selectivities were not reflected in the binding constants of representative resynthesized synthetic receptors attached to beads, which were all in the range of 500 M−1 in phosphate buffer. Moreover, this showed that, in contrast to an non‐aqueous system, the third arm of the tripod did not contribute to the binding of Ds‐Gly‐D‐Ala‐D‐Lac‐OH, since in chloroform binding constants ‐also determined on the beads‐ were observed of 11,700 M−1 and 5,400 M−1 for a tripod and tweezer receptor, respectively.
Application of QSARs: Correlation of Acute Toxicity in the Rat Following Oral or Inhalation Exposure
Authors: de Wolf Watze , Lieder Paul H. , Walker John D.
Published: September 2004

Quantitative Structure‐Activity Relationships (QSARs) based upon a lethal narcosis mechanism represent baseline or minimum toxicity, i.e. unless a chemical acts by a more specific mechanism, its toxicity will be predicted by such models. Baseline toxicity should be independent of exposure route. A toxicity ratio (TR) is defined as the ratio of the calculated baseline toxicity over the experimentally determined value. A TR‐value of approx. 1 indicates baseline toxicity. A TR‐value greater than 1 indicates excess toxicity due to the existence of a more specific mechanism of action. We investigated the possibility of extrapolation from the inhalation route to the oral route by applying the above concepts.
Strain Energies as a Steric Descriptor in QSAR Calculations
Authors: Williford Catherine J. , Stevens Erland P.
Published: September 2004

The difference between the calculated heats of formation of gauche and anti conformers of monosubstituted propanes was determined and used as a new steric parameter (AG60 value) in QSAR calculations. The dihedral angle of the gauche conformation was fixed at 60° during the calculation to force interaction of the gauche groups. AG60 values are a thermodynamically determined steric measure in contrast to the Taft steric parameter, which is based upon kinetic measurements of ester hydrolyses. In comparisons to published QSAR studies, AG60 values correlated steric effects and biological activities very similarly to the Taft parameter. The average of r2 values from five QSAR studies for the Taft parameter was 0.887, while AG60 values averaged 0.883. Direct comparison of the Taft parameter and AG60 values showed a poor correlation (r2=0.300), indicating the two parameters are fundamentally different methods of measuring steric bulk.
Molecular Dynamics of Complexes of Atosiban with Neurohypophyseal Receptors in the Fully Hydrated Phospholipid Bilayer
Authors: Ślusarz Magdalena J. , Ślusarz Rafał , Meadows Robert , Trojnar Jerzy , Ciarkowski Jerzy
Published: September 2004

The aim of our research was to get insight into the molecular mechanism of binding atosiban, a strong selective oxytocin (OT) antagonist by OT receptor (OTR) versus vasopressin V1a and V2 receptors (V1aR and V2R, respectively). The docking of ligand and interaction with receptor are dynamic events and Molecular Dynamics (MD) seems to be a proper tool for studying the mentioned processes. Therefore we describe MD of three pairs of atosiban‐receptor complexes, two complexes per each receptor, conducted in the fully hydrated 1‐palmitoyl‐2‐oleoyl‐sn‐glycero‐3‐phosphatidylcholine lipid bilayer, simulating G protein‐coupled receptors environment. We confirmed strong and specific binding of atosiban in OTR and a weaker binding of it in V1aR, on the contrary to its less specific binding in V2R, in the agreement with our preliminary results [Ślusarz et al. 2003].
QSTR with Extended Topochemical Atom Indices. 4. Modeling of the Acute Toxicity of Phenylsulfonyl Carboxylates toVibrio fischeriusing Principal Component Factor Analysis and Principal Component Regression Analysis
Authors: Roy Kunal , Ghosh Gopinath
Published: September 2004

The present paper deals with modeling of the acute toxicity of 56 phenylsulfonyl carboxylates toVibrio fischeri.Principal component factor analysis has been used as the data‐preprocessing step for the selection of independent variables for the subsequent multiple regression analysis. The statistical quality of the best model using ETA descriptors is as follows:n=56,Q2=0.726,Ra2=0.837,R=0.923,F=57.4 (df5, 50),s=0.186, AVRES=0.136. Attempt has also been made to model the data set with different non‐ETA parameters (topological indices including Wiener, HosoyaZ, molecular connectivity, kappa shape, BalabanJand E‐State parameters apart from physicochemical parameters like AlogP98, MolRef and H‐bond‐acceptor) and the best model shows the following quality:n=56,Q2=0.763,Ra2=0.798,R=0.903,F=44.3 (df 5, 50),s=0.207, AVRES=0.139. An attempt to use both ETA and non‐ETA parameters has lead to an equation which is somewhat better in statistical quality than the best ETA model:n=56,Q2=0.779,Ra2=0.861,R=0.935,F=69.4 (df5, 50),s=0.172, AVRES=0.127. Use of the ETA indices has suggested that negative contributions of steric bulk, branching, functionality of C10, functionality of chloro substituent at X1position and presence of unsaturation at the substituent(s) on C10, and positive contributions of functionality of O13and presence of substituents with electronegative atoms at R2and R3positions. Using factor scores as independent variables, principal component regression analysis has been performed and the derived relations are of excellent statistical qualities (Q2values being 0.816, 0.828 and 0.848 whileR2values being 0.894, 0.871 and 0.905 for factor scores derived from ETA, non‐ETA and combined matrices respectively) which are comparable to that (Q2andR2values being 0.790 and 0.920 respectively) of the relation generated from comparative molecular field analysis on the same data set.
Negative ion graphitised carbon nano‐liquid chromatography/mass spectrometry increases sensitivity for glycoprotein oligosaccharide analysis
Authors: Karlsson Niclas G. , Wilson Nicole L. , Wirth Hans‐Jürgen , Dawes Peter , Joshi Hiren , Packer Nicolle H.
Published: September 2004

Negative ion nano‐liquid chromatography/mass spectrometry (nano‐LC/MS) and tandem mass spectrometry (nano‐LC/MS2), using graphitised carbon as separating medium, were explored for analysing neutral and acidic O‐linked and N‐linked oligosaccharide alditols. Compared to the sensitivity of capillary LC/MS (flow rate of 6 μL/min) coupled with a conventional electrospray ionisation source, the nano‐LC/MS (flow rate of 0.6 μL/min) with a nanoflow ion source was shown to increase the sensitivity ten‐fold with a detection limit in the low‐femtomole range. The absolute signals for the [MnH]n− ions of the oligosaccharides were increased 100‐fold, enabling accumulation of high‐quality fragmentation data in MS2 mode, in which detection of low abundant sequence ions is necessary for characterisation of highly sialylated N‐linked oligosaccharides. Oligosaccharides with high numbers of sialic acid residues gave dominant fragments arising from the loss of sialic acid, and less abundant fragments from cleavage of other glycosidic bonds. Enzymatic off‐line desialylation of oligosaccharides in the low‐femtomole range prior to MS2 analysis was shown to increase the quality of the spectra. Automated glycofragment mass fingerprinting using the GlycosidIQ software confirmed the oligosaccharide sequence for both neutral desialylated as well as sialylated structures. Furthermore, the use of graphitised carbon nano‐LC/MS enabled the detection of four sialylated O‐linked oligosaccharides on membrane proteins from ovarian tissue (5 μg of total amount of protein). Copyright © 2004 John Wiley & Sons, Ltd.
Ultra‐performance liquid chromatography coupled to quadrupole‐orthogonal time‐of‐flight mass spectrometry
Authors: Plumb Robert , Castro‐Perez Jose , Granger Jennifer , Beattie Iain , Joncour Karine , Wright Andrew
Published: September 2004

Ultra‐performance liquid chromatography (UPLC) utilizes sub‐2 μm particles with high linear solvent velocities to effect dramatic increases in resolution, sensitivity and speed of analysis. The reduction in particle size to below 2 μm requires instrumentation that can operate at pressures in the 6000–15 000 psi range. The typical peak widths generated by the UPLC system are in the order of 1–2 s for a 10‐min separation. In the present work this technology has been applied to the study of in vivo drug metabolism, in particular the analysis of drug metabolites in bile. The reduction in peak width significantly increases analytical sensitivity by three‐ to five‐fold, and the reduction in peak width, and concomitant increase in peak capacity, significantly reduces spectral overlap resulting in superior spectral quality in both MS and MS/MS modes. The application of UPLC/MS resulted in the detection of additional drug metabolites, superior separation and improved spectral quality. Copyright © 2004 John Wiley & Sons, Ltd.
A20 is a potent inhibitor of TLR3‐ and Sendai virus‐induced activation of NF‐κB and ISRE and IFN‐β promoter
Authors: Wang Yan-Yi , Li Lianyun , Han Ke-Jun , Zhai Zhonghe , Shu Hong-Bing
Published: September 2004

Toll‐like receptor 3 (TLR3) recognizes dsRNA generated during viral infection and activation of TLR3 results in induction of type I interferons (IFNs) and cellular anti‐viral response. TLR3 is associated with a TIR domain‐containing adapter protein TRIF, which activates distinct downstream pathways leading to activation of NF‐κB and ISRE sites in the promoters of type I IFNs. We show here that A20, a NF‐κB‐inducible zinc finger protein that has been demonstrated to be an inhibitor of TNF‐induced NF‐κB activation and a physiological suppressor of inflammatory response, potently inhibited TLR3‐ and Sendai virus‐mediated activation of ISRE and NF‐κB and IFN‐β promoter in reporter gene assays. A20 also inhibited TRIF‐, but not its downstream signaling components TBK1‐, IKKβ‐, and IKKε‐mediated activation of ISRE and NF‐κB and IFN‐β promoter. Moreover, A20 interacted with TRIF in co‐immunoprecipitation experiments. Finally, expression of A20 could be induced at protein level by Sendai virus infection. These data suggest that A20 targets TRIF to inhibit TLR3‐mediated induction of IFN‐β transcription and functions as a feedback negative regulator for TLR3 signaling and cellular anti‐viral response.
Maintenance of bone mass and architecture in denning black bears (Ursus americanus)
Authors: Pardy Connor K. , Wohl Gregory R. , Ukrainetz Philip J. , Sawers Andrew , Boyd Steven K. , Zernicke Ronald F.
Published: September 2004

Bone mass is dramatically compromised during periods of weightlessness, inactivity, or bed rest. Animals that hibernate reduce their body temperature, heart rate and metabolic activity, and likewise lower bone turnover activity during their immobile state. Black bears Ursus americanus, however, do not hibernate, but rather overwinter by denning during which they maintain a nearly normal functional heart rate, cardiac output and temperature. Furthermore, markers of bone turnover in black bears are maintained during denning periods. Thus, the purpose of this work was to determine if the denning state of relative immobility in black bears results in changes in bone mass and bone architectural structure. Harvested forelimbs (ulna and radius) were compared between pre‐ and post‐denning black bears using X‐ray imaging, dual energy X‐ray absorptiometry, and micro‐computed tomography to quantify total distal forelimb bone mineral density, cancellous bone mineral density, bone mineral content, bone volume fraction, degree of anisotropy, structure model index, and trabecular thickness. No significant differences in any of the measured parameters were found in comparing radius and ulna from autumn and spring bears in this cross‐sectional sample, suggesting that black bears did not experience a significant change in bone mass or architecture during denning. The statistical power for detecting a significant difference (P≤ 0.05) for this sample was 0.8. The specific mechanism by which the preservation of bone was attained may be related to skeletal muscle interaction or circulating systemic hormones.
Okhotsk Sea Kashevarov Bank polynya: Its dependence on diurnal and fortnightly tides and its initial formation
Authors: Martin Seelye , Polyakov Igor , Markus Thorsten , Drucker Robert
Published: September 2004

A powerful resonance in the O1 and K1 diurnal tides occurs over the Kashevarov Bank in the Okhotsk Sea. Model studies show that this resonance creates tidal mixing and an associated vertical heat flux, both with diurnal and fortnightly components. In midwinter this flux controls the behavior of the resultant polynya; in early winter it affects the polynya formation. For the midwinter case, examination of numerical results and of imagery derived from the Special Sensor Microwave Imager (SSM/I), the advanced very high resolution radiometer (AVHRR), and the RADARSAT ScanSAR shows that the polynya area varies diurnally and fortnightly. Specifically, for the 2000 and 2001 winters, daily averaged passive microwave images clearly show a fortnightly cycle in the polynya area. At the diurnal period the model shows that the location of the maximum heat flux oscillates between the northwestern and southwestern edge of the bank and that the polynya oscillates between the western edge of the bank and being elongated in the east‐west direction over the southern edge. Passive microwave swath and AVHRR imagery show a similar polynya behavior. For the early winter case and during a period of northerly winds, synthetic aperture radar imagery shows that the polynya consists of two parts, an upwelling polynya over the bank and a secondary polynya downwind of the bank with properties similar to coastal polynyas. In the case of the secondary polynya the region of upwelled warm water over the bank serves as its northern boundary.
Improved quantification of Chinese carbon fluxes using CO2/CO correlations in Asian outflow
Authors: Suntharalingam Parvadha , Jacob Daniel J. , Palmer Paul I. , Logan Jennifer A. , Yantosca Robert M. , Xiao Yaping , Evans Mathew J. , Streets David G. , Vay Stephanie L. , Sachse Glen W.
Published: September 2004

We use observed CO2:CO correlations in Asian outflow from the TRACE‐P aircraft campaign (February–April 2001), together with a three‐dimensional global chemical transport model (GEOS‐CHEM), to constrain specific components of the east Asian CO2 budget including, in particular, Chinese emissions. The CO2/CO emission ratio varies with the source of CO2 (different combustion types versus the terrestrial biosphere) and provides a characteristic signature of source regions and source type. Observed CO2/CO correlation slopes in east Asian boundary layer outflow display distinct regional signatures ranging from 10–20 mol/mol (outflow from northeast China) to 80 mol/mol (over Japan). Model simulations using best a priori estimates of regional CO2 and CO sources from Streets et al. [2003] (anthropogenic), the CASA model (biospheric), and Duncan et al. [2003] (biomass burning) overestimate CO2 concentrations and CO2/CO slopes in the boundary layer outflow. Constraints from the CO2/CO slopes indicate that this must arise from an overestimate of the modeled regional net biospheric CO2 flux. Our corrected best estimate of the net biospheric source of CO2 from China for March–April 2001 is 3200 Gg C/d, which represents a 45% reduction of the net flux from the CASA model. Previous analyses of the TRACE‐P data had found that anthropogenic Chinese CO emissions must be ∼50% higher than in Streets et al.'s [2003] inventory. We find that such an adjustment improves the simulation of the CO2/CO slopes and that it likely represents both an underreporting of sector activity (domestic and industrial combustion) and an underestimate of CO emission factors. Increases in sector activity would imply increases in Chinese anthropogenic CO2 emissions and would also imply a further reduction of the Chinese biospheric CO2 source to reconcile simulated and observed CO2 concentrations.
Paleogene tropical Pacific: Clues to circulation, productivity, and plate motion
Authors: Moore T. C. , Backman Jan , Raffi Isabella , Nigrini Catherine , Sanfilippo Annika , Pälike Heiko , Lyle Mitchell
Published: September 2004

Stratigraphic data from 63 Deep Sea Drilling Project and Ocean Drilling Program (ODP) sites that sample the lower Neogene and Paleogene sediments of the tropical Pacific have been compiled and put on the biostratigraphic and paleomagnetic timescale refined by ODP Leg 199 scientists. Sediment accumulation rates have been calculated for ten intervals ranging in age from 10 to 56 Ma and have been plotted for the midpoint of each interval at the associated paleoposition for each site used. A fixed hot spot model was used for reconstruction of the Pacific lithospheric plate. All such reconstructed intervals show the development of a tongue of high accumulation rates associated with the oceanographic divergence at the geographic equator. The development of this equatorial band is weakest between 46 and 56 Ma, the time of the peak warmth in Paleogene climate. Possible motion of the Hawaiian hot spot or true polar wander between 46 and 56 Ma appears to have had little effect on the plate rotation estimate of the position of the equator. In addition to temporal changes in the calcite compensation depth and in productivity, the biggest change in the patterns of sediment accumulation rates in the eastern tropical Pacific was the development of a relatively strong divergence between 6° and 10°N, near the region of divergence between the modern North Equatorial Current and the North Equatorial Counter Current. Changes in the equatorial circulation appear to be associated in time with the opening and closing of oceanic gateways, particularly the complex closing of the Caribbean‐Pacific gateway.
Metrics to assess the mitigation of global warming by carbon capture and storage in the ocean and in geological reservoirs
Authors: Haugan Peter M. , Joos Fortunat
Published: September 2004

Different metrics to assess mitigation of global warming by carbon capture and storage are discussed. The climatic impact of capturing 30% of the anthropogenic carbon emission and its storage in the ocean or in geological reservoir are evaluated for different stabilization scenarios using a reduced‐form carbon cycle‐climate model. The accumulated Global Warming Avoided (GWA) remains, after a ramp‐up during the first ∼50 years, in the range of 15 to 30% over the next millennium for deep ocean injection and for geological storage with annual leakage rates of up to about 0.001. For longer time scales, the GWA may approach zero or become negative for storage in a reservoir with even small leakage rates, accounting for the CO2 associated with the energy penalty for carbon capture. For an annual leakage rate of 0.01, surface air temperature becomes higher than in the absence of storage after three centuries only.
High‐precision locations of the microseismicity preceding the 2002–2003 Mt. Etna eruption
Authors: Gambino S. , Mostaccio A. , Patanè D. , Scarfì L. , Ursino A.
Published: September 2004

To recognize possible signals of intrusive processes leading to the last 2002–2003 flank eruption at Mt. Etna, we analyzed the spatial pattern of microseismicity between August 2001 and October 2002 and calculated 23 fault plane solutions (FPSs) for shocks with magnitude greater than 2.5. By applying the double‐difference approach of Waldhauser and Ellsworth [2000] on 3D locations, we found that most of the scattered epicentral locations further collapse in roughly linear features. High‐precision locations evidenced a distribution of earthquakes along two main alignments, oriented NE‐SW to ENE‐WSW and NW‐SE, matching well both with the known tectonic and volcanic lineaments of Etna and FPSs results. Moreover, microseismicity and swarms located along the NNW‐SSE volcano‐genetic trend suggest, together with geodetic data and volcanological evidence that progressive magma refilling has occurred since February 2002.