bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis and fluorescence properties of aromatic‐aliphatic copolyamides
Authors: Ren Hongxia , Wang Yunpu , Lei Ziqiang
Published: July 2005

The aromatic‐aliphatic copolyamides were synthesized by condensation polymerization of aromatic diamine PPD (or APS, where PPD is p‐phenylene diamine and APS is aminophenyl sulfone), aliphatic diamine HDA (or EDA, where HDA is hexanediamine and EDA is ethylenediamine), and TPC (where TPC is terephthalyl chloride) with different molar ratios of aromatic diamine to aliphatic diamine. The steady‐state fluorescence of these condensed copolymers was investigated. These copolyamides exhibit strong blue‐to‐green fluorescence. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 98: 315–321, 2005
Synthesis and characterization of N‐vinyl pyrrolidone and cellulosics based functional graft copolymers for use as metal ions and iodine sorbents
Authors: Chauhan Ghanshyam S. , Singh Baljit , Kumar Suresh
Published: July 2005

To develop cost effective and eco friendly polymeric materials for enrichment and separation technologies, 1‐vinyl‐2‐pyrrolidone (N‐VP) was graft copolymerized onto cellulose, extracted from pine needles. Optimum conditions have been evaluated for the grafting of N‐VP onto cellulose and at these conditions it was also grafted onto cellulose phosphate, hydroxypropyl cellulose, cyanoethyl cellulose, and deoxyhydrazino cellulose. At the optimum grafting conditions for N‐VP, it was also cografted with maleic anhydride. Kinetics of radiochemical graft copolymerization has been studied and evaluation of the polymerization and grafting parameters as percent grafting, percent grafting efficiency, rate of polymerization, homopolymerization, and graft copolymerization have been evaluated. Graft copolymers have been characterized by elemental analysis, FTIR, and swelling studies. An attempt has been made to study sorption of some metal ions such as Fe2+ and Cu2+ and iodine on select graft copolymers to investigate selectivity in metal ion sorption and iodine sorption as a function of structural aspects of the functionalized graft copolymers to find their end uses in separation and enrichment technologies. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 98: 373–382, 2005
Anti‐bacterial and swelling properties of acrylic acid grafted and collagen/chitosan immobilized polypropylene non‐woven fabrics
Authors: Wang Chyung‐Chyung , Chen Cheng‐Chi
Published: July 2005

The various weight ratios of collagen/chitosan were used to immobilize the various grafted amounts of acrylic acid (AA) grafted polypropylene nonwoven fabric. For a given value of grafting percentage of AA and the immobilizing time period, the values of the immobilizing percentage of collagen/chitosan are increased with the increasing of chitosan contained in the mixtures of collagen/chitosan. The antibacterial properties are also increased with the increasing of chitosan in the mixtures of collagen/chitosan and the immobilizing percentage of collagen/chitosan. The crosslinking reaction between the AA‐grafted PP nonwoven fabrics and collagen/chitosan with glutaraldehyde are clearly sustained by examination from the spectra of the surface reflection infrared spectroscopy (IR). The values of water uptake and water diffusion coefficients are decreased with the increasing of chitosan in the mixtures of collagen/chitosan and the immobilizing percentages of collagen/chitosan at the same pH value of buffering water. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 98: 391–400, 2005
Complete and rapid switch from light microscopy to virtual microscopy for teaching medical histology
Authors: Krippendorf Beth B. , Lough John
Published: July 2005

During the interim between the 2003 and 2004 academic years, the cell and tissue biology and integrated medical neuroscience courses at the Medical College of Wisconsin made a complete and rapid switch from light microscopy‐ to virtual microscopy‐based histology laboratories. This switch was prompted by the difficulties in maintaining and the cost of replacing the college's microscopes and microscope slides, and primarily by the desire to promote and streamline learning for our large classes (n > 200) of first‐year medical students. A group of students who used the virtual microscope, another group of students who used the light microscope, and faculty with experience using both tools rated the effectiveness of the virtual microscope for learning and teaching. Also, to determine whether virtual microscopy affected student learning, laboratory examination scores for the 2004 class (n = 209) were compared with those of four previous classes that used light microscopes exclusively (n = 811). The switch from light microscopy to virtual microscopy was very favorably received by both students and faculty. More importantly, data from examination scores and course evaluation surveys indicated that use of the virtual microscope may significantly improve student performance and learning efficiency. Procedures for successfully implementing this change are described. Anat Rec (Part B: New Anat) 285B:19–25, 2005. © 2005 Wiley‐Liss, Inc.
The case for prepatterning in the mouse
Authors: Gardner Richard L.
Published: July 2005

In studies from several laboratories using a variety of different techniques, features of the zygote and two‐cell conceptus have been found to map nonrandomly on the blastocyst with respect to both its axis of polarity and bilateral plane. This is not what would be expected if, as is widely believed, early patterning depends entirely on positional relationships and interactions among the progeny of blastomeres that are equipotential until at least the eight‐cell stage. Rather, the implication of these findings is that prepatterning is a normal facet of development in mammals, just as it is in most other metazoa. Nevertheless, there is still no general consensus regarding the extent to which such prepatterning depends on intrinsic organization of the oocyte, as opposed to events that are contingent on fertilization. Birth Defects Research (Part C) 75:142–150, 2005. © 2005 Wiley‐Liss, Inc.
5,5′‐Diamino‐2,2′‐bipyridine: A Versatile Building Block for the Synthesis of Bipyridine/Catechol Ligands That Form Homo‐ and Heteronuclear Helicates
Authors: Albrecht Markus , Janser Ingo , Lützen Arne , Hapke Marko , Fröhlich Roland , Weis Patrick
Published: July 2005

Herein we present an improved synthesis of 5,5′‐diamino‐2,2′‐bipyridine (1) starting from the pyrrole‐protected aminopyridine 4. By standard reactions 1 can easily be transformed into the imine‐ or amide‐bridged dicatechol–bipyridine ligands L1‐H4 and L2‐H4. Whereas ligand L1 readily forms homodinuclear helicates [(L1)3Ti2]4−, the attempted formation of mono‐, tri‐, or even oligonuclear coordination compounds from this ligand did not work. However, the amide‐connected ligand L2 affords mononuclear ([(L2‐H4)PdCl2], [(L2‐H4)3Zn]2+), dinuclear ([(L2)3Ti2]4−), and heterotrinuclear coordination compounds ([(L2)3Ti2Zn]2−).
Laser Flash Photolysis Generation and Kinetic Studies of Corrole–Manganese(v)‐Oxo Intermediates
Authors: Zhang Rui , Harischandra Dilusha N. , Newcomb Martin
Published: July 2005

Corrole–manganese(v)‐oxo intermediates were produced by laser flash photolysis of the corresponding corrole‐manganese(IV) chlorate complexes, and the kinetics of their decay reactions in CH2Cl2 and their reactions with organic reductants were studied. The corrole ligands studied were 5,10,15‐tris(pentafluorophenyl)corrole (H3TPFC), 5,10,15‐triphenylcorrole (H3TPC), and 5,15‐bis(pentafluorophenyl)‐10‐(p‐methoxyphenyl)corrole (H3BPFMC). In self‐decay reactions and in reactions with substrates, the order of reactivity of (Cor)MnV(O) was TPC > BPFMC > TPFC, which is inverted from that expected based on the electron‐demand of the ligands. The rates of reactions of (Cor)MnV(O) were dependent on the concentration of the oxidant and other manganese species, with increasing concentrations of various manganese species resulting in decreasing rates of reactions, and the apparent rate constant for reaction of (TPFC)MnV(O) with triphenylamine was found to display fractional order with respect to the manganese‐oxo species. The kinetic results are consistent in part with a reaction model involving disproportionation of (Cor)MnV(O) to give (Cor)MnIV and (Cor)MnVI(O) species, the latter of which is the active oxidant. Alternatively, the results are consistent with oxidation by (Cor)MnV(O) which is reversibly sequestered in non‐reactive complexes by various manganese species.
The Dutch Resolution Variant of the Classical Resolution of Racemates by Formation of Diastereomeric Salts: Family Behaviour in Nucleation Inhibition
Authors: Dalmolen Jan , Tiemersma‐Wegman Theodora D. , Nieuwenhuijzen José W. , van der Sluis Marcel , van Echten Erik , Vries Ton R. , Kaptein Bernard , Broxterman Quirinius B. , Kellogg Richard M.
Published: July 2005

The resolution of racemates through their diastereomeric salts can be positively affected by the addition of small amounts of suitable nucleation inhibitors. This discovery is a logical extension of “Dutch Resolution”, in which equimolar amounts of resolving agents that are members of the same family (i.e., structurally related) are used. We conducted a systematic search for nucleation inhibitors of the resolving agent 1‐phenylethylamine. A wide range of amines that bear possible family resemblances to 1‐phenylethylamine was investigated. It was found that (R)‐1‐phenylbutylamine is a good inhibitor of (R)‐1‐phenylethylamine. Results of turbidity measurements showed that, for the model case of mandelic acid resolution, the chief effect of this inhibitor was to widen the metastable zone for the more soluble diastereomer. This observation is in accordance with previous experience. Further scouting for possible family members revealed a wide variation in the effectiveness of inhibitors, dependent on their structure. By far the most effective inhibitors are bifunctional 1‐phenylethylamine and/or 1‐phenylbutylamine analogues. The effect of racemic inhibitors was found to approach that of enantiomerically pure inhibitors of the same absolute configuration of the 1‐phenylethylamine used for resolution. The most effective inhibitors were tested for the resolution of a structural variety of racemates, and were shown to be broadly applicable.
Novel Enantioselective Receptors for N‐Protected Glutamate and Aspartate
Authors: Ragusa Andrea , Rossi Sara , Hayes Joseph M. , Stein Matthias , Kilburn Jeremy D.
Published: July 2005

A series of chiral bisthiourea macrocycles 1–4 have been prepared and their binding properties with various dicarboxylate salts have been examined by using NMR titration and isothermal calorimetry experiments. Macrocycle 1, in particular, favours the 1:1 binding of N‐protected L‐glutamate and aspartate, but favours 1:2 binding of the corresponding D‐amino acids in polar solvents (dimethyl sulfoxide and acetonitrile). The macrocycles, however, do not bind carboxylates at all in the less competitive solvent chloroform. The binding properties of these macrocyles are sensitive to small structural changes as demonstrated by the altered binding properties of macrocycles 2–4 compared with 1.
Dipyrrolyldiketone Difluoroboron Complexes: Novel Anion Sensors With C‐H⋅⋅⋅X− Interactions
Authors: Maeda Hiromitsu , Kusunose Yukio
Published: July 2005

1,3‐Dipyrrolyl‐1,3‐propanediones, synthesized from pyrroles and malonyl chloride, form BF2 complexes, which represent a new class of naked‐eye sensors for halide and oxoanions. The association mode for the interactions of both the pyrrolyl NH and bridging CH protons with anions was confirmed by 1H NMR chemical shifts in CD2Cl2 and supported by theoretical studies. The binding constants (Ka) were estimated as 8.1×104, 2.0×103, 3.3×102, 1.3×104, and 80 m−1 for F−, Cl−, Br−, H2PO4−, and HSO4− by UV/Vis absorption spectral changes in CH2Cl2. Augmentation of Ka compared with dipyrrolylquinoxaline for H2PO4− is much larger than those for other anions. Contrary to other anions, F− quenches the emission almost completely, which was detected by the fluorescence spectrum as well as the naked‐eye. In the case of the chloride anion complex, the formation of Cl−‐bridged 1D networks, in which anion is associated with two BF2 complexes, is observed in the solid state.
Identification of Two Isomers from an Organic Mixture by Double‐Stimulated‐Echo NMR and Construction of the DOSY Spectra by the Regularized Resolvent Transform Method
Authors: Thureau Pierre , Thévand André , Ancian Bernard , Escavabaja Philippe , Armstrong Geoffrey S. , Mandelshtam Vladimir A.
Published: July 2005

DOSY‐NMR experiments were used to characterize two structural isomers that have different shapes, but identical mass fragmentation patterns, from an organic mixture. It is shown that the spherical molecule diffuses faster than the ellipsoidal one. This distinct behaviour is tentatively explained in terms of microfriction effects from the solvent. Finally, to increase the resolution and efficiency of the 2D DOSY map construction, the data were treated with the regularized resolvent transform method. This method provides good separation for mildly overlapped peaks and requires fewer points than other classical DOSY processing methods.
Fluoroalkylation of Porphyrins: A Facile Synthesis of Trifluoromethylated Porphyrins by a Palladium‐Catalyzed Cross‐Coupling Reaction
Authors: Liu Chao , Chen Qing‐Yun
Published: July 2005

Various trifluoromethylated porphyrins can be conveniently synthesized in high yields by the reaction of brominated porphyrins with FSO2CF2COOMe/CuI in the presence of catalytic amounts of Pd2(dba)3·CHCl3/AsPh3. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Synthesis of Aliphatic [carbonyl‐11C]Esters Using [11C]Carbon Monoxide
Authors: Itsenko Oleksiy , Kihlberg Tor , Långström Bengt
Published: July 2005

Aliphatic esters were labelled with a short‐lived radionuclide, 11C with t½ = 20.3 min, at the carbonyl position using [11C]carbon monoxide via rapid (6 min) photoinduced radical‐mediated carbonylation reactions. The esters were prepared from primary, secondary, and tertiary alkyl iodides, and various alcohols, including tert‐butyl alcohol and phenol. The use of strong bases was necessary to achieve good radiochemical yields in short reaction times. Isolated decay‐corrected radiochemical yields were in the range of 40–68 %. For example, methyl hydrogen dodecanoate was labelled at the ester carbonyl in 61 % isolated decay‐corrected radiochemical yield with a specific radioactivity of 158 GBq/μmol within approximately 25 min of the production of [11C]carbon monoxide. Two (13C)substituted esters were synthesised using this method to verify the labelling position. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Differential expression of proteoglycans at central and peripheral nodes of Ranvier
Authors: Melendez‐Vasquez Carmen , Carey David J. , Zanazzi George , Reizes Ofer , Maurel Patrice , Salzer James L.
Published: July 2005

The nodes of Ranvier are regularly spaced gaps between myelin sheaths that are markedly enriched in voltage‐gated sodium channels and associated proteins. Myelinating glia play a key role in promoting node formation, although the requisite glial signals remain poorly understood. In this study, we have examined the expression of glial proteoglycans in the peripheral and central nodes. We report that the heparan sulfate proteoglycan, syndecan‐3, becomes highly enriched with PNS node formation; its ligand, collagen V, is also concentrated at the PNS nodes and at lower levels along the abaxonal membrane. The V1 isoform of versican, a chondroitin sulfate proteoglycan, is also present in the nodal gap. By contrast, CNS nodes are enriched in versican isoform V2, but not syndecan‐3. We have examined the molecular composition of the PNS nodes in syndecan‐3 knockout mice. Nodal components are normally expressed in mice deficient in syndecan‐3, suggesting that it has a nonessential role in the organization of nodes in the adult. These results indicate that the molecular composition and extracellular environment of the PNS and CNS nodes of Ranvier are significantly distinct. © 2005 Wiley‐Liss, Inc.
Simplified intersubject averaging on the cortical surface using SUMA
Authors: Argall Brenna D. , Saad Ziad S. , Beauchamp Michael S.
Published: July 2005

Task and group comparisons in functional magnetic resonance imaging (fMRI) studies are often accomplished through the creation of intersubject average activation maps. Compared with traditional volume‐based intersubject averages, averages made using computational models of the cortical surface have the potential to increase statistical power because they reduce intersubject variability in cortical folding patterns. We describe a two‐step method for creating intersubject surface averages. In the first step cortical surface models are created for each subject and the locations of the anterior and posterior commissures (AC and PC) are aligned. In the second step each surface is standardized to contain the same number of nodes with identical indexing. An anatomical average from 28 subjects created using the AC–PC technique showed greater sulcal and gyral definition than the corresponding volume‐based average. When applied to an fMRI dataset, the AC–PC method produced greater maximum, median, and mean t‐statistics in the average activation map than did the volume average and gave a better approximation to the theoretical‐ideal average calculated from individual subjects. The AC–PC method produced average activation maps equivalent to those produced with surface‐averaging methods that use high‐dimensional morphing. In comparison with morphing methods, the AC–PC technique does not require selection of a template brain and does not introduce deformations of sulcal and gyral patterns, allowing for group analysis within the original folded topology of each individual subject. The tools for performing AC–PC surface averaging are implemented and freely available in the SUMA software package. Hum Brain Mapp, 2005. © 2005 Wiley‐Liss, Inc.
Hypothesis testing in distributed source models for EEG and MEG data
Authors: Waldorp Lourens J. , Huizenga Hilde M. , Grasman Raoul P.P.P. , Böcker Koen B.E. , Molenaar Peter C.M.
Published: July 2005

Hypothesis testing in distributed source models for the electro‐ or magnetoencephalogram is generally performed for each voxel separately. Derived from the analysis of functional magnetic resonance imaging data, such a statistical parametric map (SPM) ignores the spatial smoothing in hypothesis testing with distributed source models. For example, when intending to test a single voxel, actually an entire region of voxels is tested simultaneously. Because there are more parameters than observations, typically constraints are employed to arrive at a solution which spatially smooths the solution. If ignored, it can be concluded from the hypothesis test that there is activity at some location where there is none. In addition, an SPM on distributed source models gives the illusion of very high resolution. As an alternative, a multivariate approach is suggested in which a region of interest is tested that is spatially smooth. In simulations with MEG and EEG it is shown that clear hypothesis testing in distributed source models is possible, provided that there is high correspondence between what is intended to be tested and what is actually tested. The approach is also illustrated by an application to data from an experiment measuring visual evoked fields when presenting checkerboard patterns. Hum Brain Mapp, 2005. © 2005 Wiley‐Liss, Inc.
Resting anterior cingulate activity and abnormal responses to errors in subjects with elevated depressive symptoms: A 128‐channel EEG study
Authors: Pizzagalli Diego A. , Peccoralo Lauren A. , Davidson Richard J. , Cohen Jonathan D.
Published: July 2005

Depression has been associated with dysfunctional executive functions and abnormal activity within the anterior cingulate cortex (ACC), a region critically involved in action regulation. Prior research invites the possibility that executive deficits in depression may arise from abnormal responses to negative feedback or errors, but the underlying neural substrates remain unknown. We hypothesized that abnormal reactions to error would be associated with dysfunctional rostral ACC activity, a region previously implicated in error detection and evaluation of the emotional significance of events. To test this hypothesis, subjects with low and high Beck Depression Inventory (BDI) scores performed an Eriksen Flanker task. To assess whether tonic activity within the rostral ACC predicted post‐error adjustments, 128‐channel resting EEG data were collected before the task and analyzed with low‐resolution electromagnetic tomography (LORETA) using a region‐of‐interest approach. High BDI subjects were uniquely characterized by significantly lower accuracy after incorrect than correct trials. Mirroring the behavioral findings, high BDI subjects had significantly reduced pretask gamma (36.5–44 Hz) current density within the affective (rostral; BA24, BA25, BA32) but not cognitive (dorsal; BA24′, BA32′) ACC subdivision. For low, but not high, BDI subjects pretask gamma within the affective ACC subdivision predicted post‐error adjustments even after controlling for activity within the cognitive ACC subdivision. Abnormal responses to errors may thus arise due to lower activity within regions subserving affective and/or motivational responses to salient cues. Because rostral ACC regions have been implicated in treatment response in depression, our findings provide initial insight into putative mechanisms fostering treatment response. Hum Brain Mapp, 2005. © 2005 Wiley‐Liss, Inc.
Word and nonword repetition in bilingual subjects: A PET study
Authors: Klein Denise , Watkins Kate E. , Zatorre Robert J. , Milner Brenda
Published: July 2005

Learning a specific skill during childhood may partly determine the functional organization of the adult brain. This hypothesis led us to study brain activation patterns using positron emission tomography (PET), in which we compared word and nonword repetition in 10 right‐handed native English‐speakers (L1) who were proficient in their second language, French (L2), which was learned after the age of 5 years. Regional cerebral blood flow (rCBF) was measured by the H215O intravenous bolus method with intersubject averaging and coregistration of magnetic resonance and PET images. A comparison of CBF changes when repeating words in L2 with those seen when repeating words in (L1) demonstrated that the pattern of CBF was similar across the two conditions, with several significant CBF differences in the vicinity of the left insular cortex, ventral premotor region, and in the striatum. We hypothesize that these regions are activated when subjects are required to repeat known words, showing increased activity when there are increased articulatory demands imposed by speaking L2. Comparisons of nonword repetition in L1 and L2 revealed increased activity for L2 in the left ventral premotor region and in the cerebellum; rCBF increases were also observed in these regions in both L1 and L2 with increased number of syllables and increased articulatory complexity, suggesting a role for these regions in the complex motor control needed for the production of novel sequences. Hum Brain Mapp, 2005. © 2005 Wiley‐Liss, Inc.
Activation of the left planum temporale in pitch processing is shaped by language experience
Authors: Xu Yisheng , Gandour Jackson , Talavage Thomas , Wong Donald , Dzemidzic Mario , Tong Yunxia , Li Xiaojian , Lowe Mark
Published: July 2005

Implicit, abstract knowledge acquired through language experience can alter cortical processing of complex auditory signals. To isolate prelexical processing of linguistic tones (i.e., pitch variations that convey part of word meaning), a novel design was used in which hybrid stimuli were created by superimposing Thai tones onto Chinese syllables (tonal chimeras) and Chinese tones onto the same syllables (Chinese words). Native speakers of tone languages (Chinese, Thai) underwent fMRI scans as they judged tones from both stimulus sets. In a comparison of native vs. non‐native tones, overlapping activity was identified in the left planum temporale (PT). In this area a double dissociation between language experience and neural representation of pitch occurred such that stronger activity was elicited in response to native as compared to non‐native tones. This finding suggests that cortical processing of pitch information can be shaped by language experience and, moreover, that lateralized PT activation can be driven by top‐down cognitive processing. Hum Brain Mapp, 2005. © 2005 Wiley‐Liss, Inc.
Water and the Huisgen Cycloaddition Reaction: A Focus on Polar Contributions to the Transition State in the Reactions of Dicyano(phthalazinium)methanide with Substituted Styrenes and Benzylidene Acetones
Authors: Butler Richard N. , Coyne Anthony G. , Cunningham William J. , Moloney Eamon M. , Burke Luke A.
Published: July 2005

Synthetic and kinetic studies on the 1,3‐dipolar cycloaddition reactions of dicyano(phthalazin‐2‐ium‐2‐yl)methanide (1) with some substituted styrenes and ‘benzylidene acetones’ in MeCN and H2O containing 10 mol‐% of MeCN are reported. The kinetic data were supported by theoretical calculations. The major products from styrenes were exo‐2‐aryl‐1,2,3,10b‐tetrahydropyrrolo[2,1‐a]phthalazine‐3,3‐dicarbonitriles 3, and, from ‘benzylidene acetones’, 1‐endo,2‐exo‐2‐acetyl‐1‐aryl‐1,2,3,10b‐tetrahydropyrrolo[2,1‐a]phthalazine‐3,3‐dicarbonitriles 7. There was no indication that the cycloadditon transition states were more polar in the aqueous environment than in MeCN.
Novel Sulfonamide Derivatives as Inhibitors of Histone Deacetylase
Authors: Finn Paul W. , Bandara Morwena , Butcher Chris , Finn Angela , Hollinshead Ruth , Khan Nagma , Law Norman , Murthy Sreenivasa , Romero Rosario , Watkins Clare , Andrianov Victor , Bokaldere Rasma M. , Dikovska Klara , Gailite Vija , Loza Einars , Piskunova Irina , Starchenkov Igor , Vorona Maxim , Kalvinsh Ivars
Published: July 2005

Inhibition of the enzyme histone deacetylase (HDAC) is emerging as a novel approach to the treatment of cancer. A series of novel sulfonamide derivatives were synthesized and evaluated for their ability to inhibit human HDAC. Compounds were identified which are potent enzyme inhibitors, with IC50 values in the low nanomolar range against enzyme obtained from HeLa cell extracts, and with antiproliferative effects in cell culture. Extensive characterization of the structure–activity relationships of this series identified key requirements for activity. These include the direction of the sulfonamide bond and substitution patterns on the central phenyl ring. The alkyl spacer between the aromatic head group and the sulfonamide functionality also influenced the HDAC inhibitory activity. One of these compounds, m11.1, also designated PXD101, has entered clinical trials for solid tumors and haematological malignancies.
Stereoselective Cyclopropanation of 2‐[(S)‐(4‐Methylphenyl)sulfinyl]cyclopent‐2‐en‐1‐one with Sulfur Ylides and α‐Halo Carbanions. Preliminary Communication
Authors: Mikołajczyk Marian , Midura Wanda H. , Michedkina Elena , Filipczak Agnieszka D. , Wieczorek Michał W.
Published: July 2005

The cyclopropanation of the title compound (S)‐2 with various sulfur ylides has been examined. The reaction with methylenesulfonium ylides gave the corresponding cyclopropanes 4 with low diastereoselectivity. The formation of the second product 5 arising from the subsequent methylenation of the CO group was also observed. A clean cyclopropanation of (S)‐2 took place with ethyl (dimethylsulfanylidene)acetate affording the cyclopropanes 6, with high π‐facial selectivity, but low endo/exo ratio. A high endo/exo selectivity, but low π‐facial selectivity was observed in the reaction of (S)‐2 with (2‐ethoxy‐2‐oxoethyl)(diphenyl)sulfonium tetrafluoroborate. The use of α‐bromoacetate carbanion as the cyclopropanation reagent resulted in the formation of 6 with very high facial and endo/exo‐selectivity. In a proposed explanation of the stereochemical outcome of the cyclopropanations investigated, the ground‐state conformation of the sulfoxide 2 and the transition‐state structure of the initial addition step were taken into account.
A Novel Coupling 1,3‐Dipolar Cycloaddition Sequence as a Three‐Component Approach to Highly Fluorescent Indolizines
Authors: Rotaru Alexandru V. , Druta Ioan D. , Oeser Thomas , Müller Thomas J. J.
Published: July 2005

Indolizines 4 and biindolizines 6 can be synthesized in moderate yields in a consecutive one‐pot three‐component process by a coupling/1,3‐dipolar cycloaddition sequence of a (hetero)arenecarbonyl chloride 1, a terminal alkyne 2, and a suitable 1‐(2‐oxoethyl) pyridinium bromide 3 or 5, respectively (Schemes 1 and 2). After the Sonogashira coupling, a [2+3] cycloaddition of the in situ formed pyridinium ylide, an allyl‐type 1,3‐dipole, furnishes a cycloadduct that is instantaneously oxidatively aromatized to give the highly fluorescent indolizine derivatives that were unambiguously characterized by an X‐ray‐structure analysis of compound 4d (Fig. 1). Additionally, fluorescence studies with pyridinyl‐substituted representatives reveal not only that indolizines and biindolizines are highly interesting fluorescence dyes but that their fluorescence color can also be reversibly switched upon altering the pH of the medium.
1,3‐Dipolar Cycloaddition Reactions of Organic Azides with Morpholinobuta‐1,3‐dienes and with an α‐Ethynyl‐enamine
Authors: Brunner Martina , Maas Gerhard , Klärner Frank‐Gerrit
Published: July 2005

The cycloaddition of organic azides with some conjugated enamines of the 2‐amino‐1,3‐diene, 1‐amino‐1,3‐diene, and 2‐aminobut‐1‐en‐3‐yne type is investigated. The 2‐morpholinobuta‐1,3‐diene 1 undergoes regioselective [3+2] cycloaddition with several electrophilic azides RN3 2 (a, R=4‐nitrophenyl; b, R=ethoxycarbonyl; c, R=tosyl; d, R=phenyl) to form 5‐alkenyl‐4,5‐dihydro‐5‐morpholino‐1H‐1,2,3‐triazoles 3 which are transformed into 1,5‐disubstituted 1H‐triazoles 4a,d or α,β‐unsaturated carboximidamide 5 (Scheme 1). The cycloaddition reaction of 4‐[(1E,3Z)‐3‐morpholino‐4‐phenylbuta‐1,3‐dienyl]morpholine (7) with azide 2a occurs at the less‐substituted enamine function and yields the 4‐(1‐morpholino‐2‐phenylethenyl)‐1H‐1,2,3‐triazole 8 (Scheme 2). The 1,3‐dipolar cycloaddition reaction of azides 2a–d with 4‐(1‐methylene‐3‐phenylprop‐2‐ynyl)morpholine (9) is accelerated at high pressure (ca. 7–10 kbar) and gives 1,5‐disubstituted dihydro‐1H‐triazoles 10a,b and 1‐phenyl‐5‐(phenylethynyl)‐1H‐1,2,3‐triazole (11d) in significantly improved yields (Schemes 3 and 4). The formation of 11d is also facilitated in the presence of an equimolar quantity of tBuOH. The three‐component reaction between enamine 9, phenyl azide, and phenol affords the 5‐(2‐phenoxy‐2‐phenylethenyl)‐1H‐1,2,3‐triazole 14d.
Palladium‐Catalyzed Amination of 3,5‐Dihalopyridines – a Convenient Route to New Polyazamacrocycles
Authors: Averin Alexei D. , Ulanovskaya Olesya A. , Fedotenko Ilya A. , Borisenko Anatolii A. , Serebryakova Marina V. , Beletskaya Irina P.
Published: July 2005

Pd‐Catalyzed amination of 3,5‐dibromo‐ and 3,5‐dichloropyridine (1a and 1b, resp.) with linear polyamines 2 leads to the formation of a new family of pyridine‐containing macrocycles 3 with an ‘exo’‐oriented pyridine N‐atom (Schemes 1 and 2). The dependence of the macrocycle yield on the nature of the halogen atom, the length of the polyamine chain and C/N atom ratio, and the composition of the catalytic system is studied. The synthesis of mono‐ and bis(5‐halopyridin‐3‐yl)‐substituted polyamines 4, 5, 8, 9, and of 3,5‐bis(polyamino)‐substituted pyridines 6 is described (Schemes 3 and 4), and the use of these compounds as intermediates on the way to the macrocycles 7, 16, and 18 with larger cavity (‘cyclodimers’ and ‘cyclotrimers’) is demonstrated (Schemes 5–10).
A novel star PEG–derived surface coating for specific cell adhesion
Authors: Groll Juergen , Fiedler Joerg , Engelhard Erika , Ameringer Thomas , Tugulu Stefano , Klok Harm‐Anton , Brenner Rolf E. , Moeller Martin
Published: July 2005

In this study a novel approach for the coating and functionalization of substrates for cell culture and tissue engineering is presented. Glass, silicon, and titanium panes were coated with an ultrathin film (30 ± 5 nm) of reactive star‐shaped poly(ethylene glycol) prepolymers (Star PEG). Homogeneity of the films was checked by optical microscopy and scanning force microscopy. These coatings prevent unspecific protein adsorption as monitored by fluorescence microscopy and ellipsometry. In order to allow specific cell adhesion the films were modified with linear RGD peptides (gRGDsc) in different concentrations. After sterilization, fibroblast, SaOS, and human mesenchymal stem cells (hMSC) were seeded on these substrates. Cell adhesion, spreading, and survival was observed for up to 30 days on linear RGD peptide (gRGDsc)‐modified coatings, whereas no cell adhesion could be detected on unmodified Star PEG layers. By variation of the RGD concentration within the film the amount of cells that became adhesive could be controlled. When differentiation conditions are used for cultivation of hMSCs the cells show the expression of osteogenic marker genes after 14 days which is comparable to cultivation on cell culture plastic. Thus, the Star PEG/RGD film did not negatively influence the differentiation process. The high flexibility of the system considering the incorporation of biologically active compounds opens a broad field of future experiments. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res, 2005
Complement inhibition reduces material‐induced leukocyte activation with PEG modified polystyrene beads (Tentagel™) but not polystyrene beads
Authors: Gorbet M. B. , Sefton M. V.
Published: July 2005

With isolated leukocytes, inhibiting complement reduced material‐induced leukocyte activation (CD11b) with polyethylene glycol modified polystyrene beads (PS‐PEG), but not with polystyrene beads (PS). The PS‐PEG beads (TentaGel™) were complement activating as measured by SC5b‐9 levels consistent with the sensitivity of these beads to leukocyte inhibition with complement inhibitors. Following contact with PS and PS‐PEG beads, isolated leukocytes in plasma and in the absence in platelets were found to significantly upregulate CD11b, while TF expression and exposure of phosphatidylserine remained at background levels. Complement inhibition by means of sCR1 partially reduced CD11b upregulation on PS‐PEG beads, but had no effect with PS beads. Pyridoxal‐5‐phosphate (P5P) was able to significantly reduce both CD11b upregulation and exposure of phosphatidylserine with PS‐PEG beads, although it did not appear to inhibit SC5b‐9 production. Pentamidine and NAAGA inhibited complement and were effective in reducing CD11b upregulation with both PS and PS‐PEG. However, they also had an inhibitory effect on leukocyte signaling mechanisms, precluding their utility for further study in this context. Leukocyte adhesion occurred to similar extents on both PS and PS‐PEG beads. While sCR1 and P5P blocked adhesion and activation (for adherent leukocytes) on PS‐PEG beads, they had no effect on leukocytes adherent to PS beads. The role of complement in leukocyte activation and adhesion was found to be material‐dependent. Thus, leukocyte‐material compatibility may be resolved by complement inhibition in some but not all cases. For these other materials (example here was PS), other mechanisms, such as fibrinogen adsorption and direct leukocyte release, may need exploitation to minimize leukocyte activation and adhesion. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res, 2005
Increased osteoblast function on PLGA composites containing nanophase titania
Authors: Webster Thomas J. , Smith Tyler A.
Published: July 2005

Nanotechnology creates materials that potentially outperform, at several boundaries, existing materials in terms of mechanical, electrical, catalytic, and optical properties. However, despite their promise to mimic the surface roughness cells experience in vivo, the use of nanophase materials in biological applications remains to date largely unexplored. The objective of the present in vitro study was, therefore, to determine whether when added to a polymer scaffold, nanophase compared to conventional ceramics enhance functions of osteoblasts (or bone‐forming cells). Results from this study provided the first evidence that functions (specifically, adhesion, synthesis of alkaline phosphatase, and deposition of calcium‐containing mineral) of osteoblasts increased on poly‐lactic‐co‐glycolic acid (PLGA) scaffolds containing nanophase compared to conventional grain size titania with greater weight percentage (from 10–30 wt %). Because the chemistry, material phase, porosity (%), and pore size of the composites were similar, this study implies that the surface features created by adding nanophase compared to conventional titania was a key parameter that enhanced functions of osteoblasts. In this manner, the study adds another novel property of nanophase ceramics: their ability to promote osteoblast functions in vitro when added to a polymer scaffold. For this reason, nanophase ceramics (and nanomaterials in general) deserve further attention as orthopedic tissue engineering materials. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res, 2005
Mineralization of SaOS‐2 cells on enzymatically (silicatein) modified bioactive osteoblast‐stimulating surfaces
Authors: Schröder Heinz C. , Boreiko Oleksandra , Krasko Anatoli , Reiber Andreas , Schwertner Heiko , Müller Werner E. G.
Published: July 2005

There is a demand for novel bioactive supports in surgery, orthopedics, and tissue engineering. The availability of recombinant silica‐synthesizing enzyme (silicatein) opens new possibilities for the synthesis of silica‐containing bioactive surfaces under ambient conditions that do not damage biomolecules like proteins. Here it is shown that growth of human osteosarcoma SaOS‐2 cells on cluster plates precoated with Type 1 collagen is not affected by additional coating of the plates with the recombinant silicatein and incubation with its enzymatic substrate, tetraethoxysilane (TEOS). However, the enzymatic modification of the plates by biosilica deposition on the protein‐coated surface caused a marked increase in calcium phosphate formation of SaOS‐2 cells as revealed by alizarin red‐S staining to quantify calcium mineral content. The increased occurrence of calcium‐phosphate nodules on the modified surface was also observed by scanning electron microscopy. These results suggest that by supporting calcium‐phosphate deposition in vitro, biosilica (silicatein)‐modified surfaces are potentially bioactive in vivo, by stimulating osteoblast mineralization function. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2005
Biological properties of photocrosslinked alginate microcapsules
Authors: Shen Feng , Li Anna Aihua , Cornelius Rena M. , Cirone Pasquale , Childs Ronald F , Brash John L. , Chang Patricia L.
Published: July 2005

An alternative form of gene therapy using recombinant cell lines delivering therapeutic products encapsulated in alginate hydrogel has proven effective in treating many murine models. The lack of long‐term capsule stability has led to a new strategy to reinforce the microcapsules with a photopolymerized interpenetrating covalent network of N‐vinylpyrrolidone (NVP) and sodium acrylate. Here the properties for potential application in gene therapy are reported. In assessing potential toxicity of the unpolymerized residues, HPLC showed that even after 1 week of washing, no toxic monomers could be detected. Their ability to sustain cell growth was monitored with growth of the encapsulated cells in vitro and in vivo. Although the initial photopolymerization caused significant cell damage, the cells were able to recover normal growth rates thereafter. After implanting into mice, the NVP‐modified capsules showed a high level of biocompatibility as measured by hematological and biochemical functional tests. There was also no difference in the amount and type of plasma proteins adsorbing to the NVP‐modified and the classical alginate capsules, thus indicating their similar biological compatibility. Both in vitro and in vivo tests confirmed that the NVP‐modified capsules were more resistant to osmotic stress than the alginate microcapsules. Furthermore, when applied to the treatment of a murine model of human cancer by delivering encapsulated cells secreting angiostatin, the NVP‐modified microcapsules suppressed tumor growth as successfully as the regular alginate microcapsules. In conclusion, the covalently modified microcapsules have shown a high level of biocompatibility, safety, increase in stability, and clinical efficacy for use as immunoisolation devices in gene therapy. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2005
Matrix physicochemical properties affect activity of entrapped chlorophyllase
Authors: Yi Yunyu , Kermasha Selim , Neufeld Ronald
Published: July 2005

Chlorophyllase, a membrane glycoprotein, was entrapped in various matrices, including alginate, alginate–silicate mixed gel, TMOS‐based sol–gel, and their hydrophobically‐modified counterparts. Chlorophyllase activity was affected by the physicochemical properties of the matrix, demonstrating lower activity in organically‐modified matrices compared with the corresponding hydrophilic matrices. The advantage of adopting organically‐modified matrices to facilitate the transfer of hydrophobic substrate is likely compromised by detrimental interaction between chlorophyllase and the hydrophobic components. This hypothesis is at least partly substantiated by the negligible activity demonstrated by free chlorophyllase in hydrophobic micellar media. Even though activity yields exceeded 50% in alginate beads, the release profile reveals that alginate matrix is too porous to retain chlorophyllase. Although alginate–silicate mixed gel more effectively confined chlorophyllase in the matrix, only 16% of the activity was recovered. In contrast, inorganic sol–gel yielded a chlorophyllase preparation with mass yield above 90%, and activity yield above 50%. Doping additives did not improve activity yield, which could be explained by the lower specific surface area and pore volume, and hence possible restricted accessibility of chlorophyllase by its substrate. Water/silane ratio was found to affect the sol–gel‐entrapped chlorophyllase activity by influencing the gelation time and physical properties of the gel. Copyright © 2005 Society of Chemical Industry
Electrochemical removal of ammonia, chemical oxygen demand and energy consumption from aquaculture waters containing different marine algal species
Authors: Wijesekara RG Saman , Nomura Nakao , Matsumura Masatoshi
Published: July 2005

Phytoplankton over‐blooming and consequent die‐off is one of the major contributory factors for ammonia and chemical oxygen demand (COD) loadings. In this work, electrolysis technology was applied to determine its ability to remove ammonia and total chemical oxygen demand (TCOD) in both laboratory‐scale batch and continuous systems. Under an initially set voltage of 5 V, a constant current of 0.1 A was applied and different retention times were used for ammonia‐removal experiments. Results showed that these conditions are not satisfactory in removing TCOD loadings contributed by algal cells. However, a retention time of 35.7 min was sufficient to remove 100% ammonia from algal‐uncontaminated waters. Ammonia removals in waters containing Chlorella spp and Isochrysis spp were 87 and 68%, respectively, after 140 min of electrolysis. Energy consumption for ammonia removal in algal‐free water was 50 W mg−1 of ammonia. For waters containing Chlorella spp and Isochrysis spp energy consumptions were 67 and 85 W mg−1 of ammonia, respectively. Interestingly, the applied mild electrolysis condition was just sufficient to control excess algal blooming and ammonia without increasing the dissolved COD and chlorine in shrimp grow‐out ponds. This minimizes operating costs due the process requiring less energy. Furthermore, it was also found that electrolysis does not lower alkalinity. Copyright © 2005 Society of Chemical Industry
Developmental neurotoxicology
Authors: Bondy Stephen C. , Campbell Arezoo
Published: July 2005

The developing brain has a distinctive set of characteristics that make it unusually sensitive to damage by toxic agents. Mechanistic understanding of the vulnerability of the immature nervous system to various chemicals is important from a preventive perspective but has also frequently given us new insights into maturation of neural circuitry. This review examines some of the developmental consequences of contact with various exogenous agents, including metals, solvents, pharmaceuticals, and natural products. This review emphasizes how subtle suboptimal brain function rather than acute toxicity can be a consequence of chemical exposures occurring during ontogenesis. The rate of brain aging may be influenced by events taking place in embryogenesis, following a prolonged asymptomatic period. The potential for appearance of adverse effects after prolonged latent periods is underscored. © 2005 Wiley‐Liss, Inc.
Direct profiling of the cerebellum by matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry: A methodological study in postnatal and adult mouse
Authors: Laurent Claudine , Levinson Douglas F. , Schwartz Sarah A. , Harrington Peter B. , Markey Sanford P. , Caprioli Richard M. , Levitt Pat
Published: July 2005

Matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry (MALDI MS) can detect substantial changes in expression of proteins in tissues, such as cancer cells. A more challenging problem is detecting the smaller changes expected in normal development or complex diseases. Here we address methodological issues regarding the acquisition and analysis of MALDI MS data from tissue sections, in a study of mouse cerebellum at different stages of development. Sections of the cerebellar cortex were analyzed at the peak of granule neuron production [postnatal day (P) 7], during synapse formation (P14), and in adults. Data were acquired (Voyager‐DE™ STR Biospectrometry Workstation; seven acquisitions of 50 shots per section, 3.5–50 kDa), preprocessed (Data Explorer 4.3), and averaged. Among 846 peaks detected, in at least 50% of at least one group, 122 showed significant group differences (Kruskal‐Wallis ANOVA) after Bonferroni correction. Factor analyses revealed two age‐related factors, possibly reflecting gradients of expression during development. Predictive analysis of microarrays generated a model from half of the sample that correctly predicted developmental groups for the second half. Intraclass correlation coefficients, measuring within‐mouse consistency of peak heights from three tissue sections, were acceptable at lower m/z and for larger peaks at higher m/z. Low mass was the best predictor of significant group differences. The analysis demonstrates that MALDI MS of normal tissue sections at different ages can detect consistent, significant group differences. Further work is needed to increase the sensitivity of the methods and to apply them reliably to brain regions and to subproteomes with relevance to diverse brain functions and diseases. © 2005 Wiley‐Liss, Inc.