bluuebunny/crossref_metadata_2025 huggingface dataset:
Solid‐Phase Synthesis of a β3‐Icosapeptide Containing the Homologs of the Twenty Common Proteinaceous Amino Acids. Preliminary Communication
Authors: Kimmerlin Thierry , Seebach Dieter
Published: July 2003

An icosapeptide, 1, containing the β3‐amino acid residues with the 20 proteinogenic side chains has been assembled by manual solid‐phase synthesis, according to the Fmoc strategy. The sequence was chosen in such a way that a possible 314‐helical conformation (secondary structure) would be stabilized by salt bridges and have an amphipathic character (Fig. 1,a), and the N‐terminal β3hCys would lend itself to thioligations and disulfide formation (2 and 3, in Figs. 1 and 2). The products 1–3 were pure according to RP‐HPLC, NMR, and MS analysis (Fig. 1,b and c, Fig. 2,c and d, and Fig. 3). With due caution, the CD spectra in aqueous solution (pH 7) and in MeOH (Fig. 4), with normalized Cotton effects θ =−14000 to −16000 [deg⋅cm2⋅dmol−1] between 209 and 210 nm, might be taken as an evidence for the presence of 314‐helical conformations. An evaluation of the data from a 700‐MHz 2D‐NMR measurement of the disulfide 2 in CD3OH is in progress.
Three Novel Triterpenoids from the Aerial Part of Helwingia chinensis
Authors: Lai Guo‐Fang , Wang Yi‐Fen , Lu Chun‐Hua , Cao Jian‐Xin , Xu Yun‐Long , Luo Shi‐De
Published: July 2003

Three novel triterpenoids named chinenols A–C (1–3), together with two known compounds, glutin‐5‐en‐3β‐ol (4) and daucosterol (5), were isolated from the aerial part of Helwingia chinensis Batal. The structures of 1–3 were determined on the basis of their HR‐EI‐MS, IR, 1H‐ and 13C‐NMR (DEPT), and 2D (HMQC, HMBC, NOESY) data. Compounds 1–3 and 5 showed inhibition activity in an antibacterial assay.
Synthesis and Conformational Switching of Partially and Differentially Bridged Resorcin[4]arenes Bearing Fluorescent Dye Labels. Preliminary Communication
Authors: Azov Vladimir A. , Diederich François , Lill Yoriko , Hecht Bert
Published: July 2003

We report the synthesis of modified Cram‐type cavitands bearing one or two fluorescent labels for single‐molecule spectroscopic studies of vasekite conformational switching (Scheme 3). Syntheses were performed by stepwise bridging of the four couples of neighboring H‐bonded OH groups of resorcin[4]arene bowls (Schemes 2 and 3). The new substitution patterns enable the construction of a large variety of future functional architectures. 1H‐NMR Investigations showed that the new partially and differentially bridged cavitands feature temperature‐ and pH‐triggered vasekite conformational isomerism similar to symmetrical cavitands with four identical quinoxaline bridges (Table). It was discovered that vasekite switching of cavitands is strongly solvent‐dependent.
Two New and a Known Compound from Lawsonia inermis
Authors: Siddiqui Bina S. , Kardar M. Nadeem , Ali S. Tariq , Khan Shazia
Published: July 2003

A new obtusafuran derivative, lawsonicin (1), and a new naphthaquinone, lawsonadeem (2), along with a known constituent, vomifoliol (3), were isolated from the aerial parts of Lawsonia alba and characterized by chemical transformation and spectroscopic experiments, including 2D‐NMR techniques.
Development of a New Class of Inhibitors for the Malarial Aspartic Protease Plasmepsin II Based on a Central 7‐Azabicyclo[2.2.1]heptane Scaffold
Authors: Carcache David A. , Hörtner Simone R. , Seiler Paul , Diederich François , Dorn Arnulf , Märki Hans Peter , Binkert Christoph , Bur Daniel
Published: July 2003

Plasmepsin II (PMII), a malarial aspartic protease involved in the catabolism of hemoglobin in parasites of the genus Plasmodium, and renin, a human aspartic protease, share 35% sequence identity in their mature chains. Structures of 4‐arylpiperidine inhibitors complexed to human renin were reported by Roche recently. The major conformational changes, compared to a structure of renin, with a peptidomimetic inhibitor were identified and subsequently modeled in a structure of PMII (Fig. 1). This distorted structure of PMII served as active‐site model for a novel class of PMII inhibitors, according to a structure‐based de novo design approach (Fig. 2). These newly designed inhibitors feature a rigid 7‐azabicyclo[2.2.1]heptane scaffold, which, in its protonated form, is assumed to undergo ionic H‐bonding with the two catalytic Asp residues at the active site of PMII. Two substituents depart from the scaffold for occupancy of either the S1/S3 or S2′‐pocket and the hydrophobic flap pocket, newly created by the conformational changes in PMII. The inhibitors synthesized starting from N‐Boc‐protected 7‐azabicyclo[2.2.1]hept‐2‐ene (6; Schemes 1–5) displayed up to single‐digit micromolar activity (IC50 values) toward PMII and good selectivity towards renin. The clear structureactivity relationship (SAR; Table) provides strong validation of the proposed conformational changes in PMII and the occupancy of the resulting hydrophobic flap pocket by our new inhibitors.
A New Class of Inhibitors for the Malarial Aspartic Protease Plasmepsin II Based on a Central 11‐Azatricyclo[6.2.1.02,7]undeca‐2,4,6‐triene Scaffold
Authors: Carcache David A. , Hörtner Simone R. , Bertogg Andreas , Diederich François , Dorn Arnulf , Märki Hans Peter , Binkert Christoph , Bur Daniel
Published: July 2003

A new class of nonpeptidic inhibitors of the malarial aspartic protease plasmepsin II (PMII) with up to single‐digit micromolar activities (IC50 values) was developed by structure‐based de novo design. The active‐site matrix used in the design was based on an X‐ray crystal structure of PMII, onto which the major conformational changes seen in the structure of renin upon complexation of 4‐arylpiperidines – including the unlocking of a new hydrophobic (flap) pocket – were modeled. The sequence identity of 35% between mature renin and PMII had prompted us to hypothesize that an induced‐fit adaptation around the active site as observed in renin might also be effective in PMII. The new inhibitors contain a central 11‐azatricyclo[6.2.1.02,7]undeca‐2(7),3,5‐triene core, which, in protonated form, undergoes ionic H‐bonding with the two catalytic Asp residues at the active site of PMII (Figs. 1 and 2). This tricyclic scaffold is readily prepared by a DielsAlder reaction between an activated pyrrole and a benzyne species generated in situ (Scheme 1). Two substituents with naphthyl or 1,3‐benzothiazole moieties are attached to the central core (Schemes 1–4) for accommodation in the hydrophobic flap and S1/S3 (or S2′, depending on the optical antipode of the inhibitor) pockets at the active site of the enzyme. The most‐potent inhibitors (±)‐19a–19c (IC50 3–5 μM) and (±)‐23b (2 μM) (Table) bear an additional Cl‐atom on the 1,3‐benzothiazole moiety to fully fill the rear of the flap pocket. Optimization of the linker between the tricyclic scaffold and the 1,3‐benzothiazole moiety, based on detailed conformational analysis (Figs. 3 and 4), led to a further small increase in inhibitory strength. The new compounds were also tested against other aspartic proteases. They were found to be quite selective against renin, while the selectivity against cathepsin D and E, two other human aspartic proteases, is rather poor (Table). The detailed SARs established in this investigation provide a valuable basis for the design of the next generations of more‐potent and ‐selective PMII inhibitors with potential application in a new antimalarial therapy.
Synthesis and Evaluation as Glycosidase Inhibitors of Carbasugar‐Derived Spirodiaziridines, Spirodiazirines, and Spiroaziridines
Authors: Kapferer Peter , Birault Véronique , Poisson Jean‐François , Vasella Andrea
Published: July 2003

The spirodiaziridines 6 and 9, potential inhibitors of α‐ and β‐glucosidases, were prepared from the validoxylamine A‐derived cyclohexanone 5. The trimethylsilyl protecting groups of 5 are crucial for the formation of 6 in good yields. Oxidation of 6 gave 7. The diaziridine 6 (pKHA=2.6) and the diazirine 7 did not inhibit the β‐glucosidases from almonds, the β‐glucosidase from Caldocellum saccharolyticum, and the α‐glucosidase from yeast. The N‐benzyl diaziridine 9 is a very weak inhibitor of the α‐glucosidase, but did not inhibit the β‐glucosidases. To see whether the weak inhibition is due to the low basicity of the diaziridines or to geometric factors, we prepared the spiro‐aziridines 21 and 25 and 1‐epivalidamine (32). The known cyclohexanone 10 was methylenated and epoxidised to 16 and 17. Azide opening of 16 and 17, mesylation, LiAlH4 reduction, and deprotection gave the aziridines 21 and 25 respectively. 1‐Epivalidamine (32) was prepared from the known carba‐glucose 29. The aziridine 25 (pKHA=6.8) is a weak irreversible inhibitor of the β‐glucosidase from Caldocellum saccharolyticum and a weak reversible inhibitor of the α‐glucosidase from yeast, but did not inhibit the β‐glucosidases from almonds. The poorly stable aziridine 21 weakly inhibited the three enzymes. Similarly, 1‐epivalidamine (pKHA=8.4) proved only a weak inhibitor. The known cyclopentylamine 34 (pKHA=7.9), however, is a micromolar inhibitor of these enzymes. The much stronger inhibition by 34 is related to the pseudoaxial orientation of its amino group.
Hydrogel Formation Using New L‐Lysine‐Based Low‐Molecular‐Weight Compounds with Positively Charged Pendant Chains
Authors: Suzuki Masahiro , Yumoto Mariko , Kimura Mutsumi , Shirai Hirofusa , Hanabusa Kenji
Published: July 2003

Low‐molecular‐weight compounds based on L‐lysine with alkylpyridinium or ‐imidazolium groups have been synthesized and studied for their gelation behavior in H2O. Most compounds formed gels below a concentration of 2.5 weight‐%, the pyridinium bromide 2a and the 1‐methyl‐1H‐imidazolium bromide 3 even at 0.1 weight‐%. The minimum gel concentration (MGC) necessary for hydrogelation increased with increasing length of the Lys Nα‐alkanoyl chain, but the gelation ability concomitantly decreased. Electron‐microscopic images demonstrated that these hydrogelators create a three‐dimensional network in H2O by entanglement of self‐assembled nanofibers. A fluorescence study with 8‐anilinonaphthalene‐1‐sulfonic acid (ANS) proved that some hydrophobic aggregates are formed at hydrogelator concentrations below an MGC of less than 50 μM (0.004%). FT‐IR, 1H‐NMR, and Fluorescence studies indicated that the driving forces for the self‐assembly into nanofibers are mainly hydrophobic interactions and H‐bonding between amide groups.
Convenient Entry to α‐Amino‐β‐hydroxy‐γ‐methyl Carboxylic Acids. Diastereoselective Formation and Directed Homogeneous Hydrogenation of 3‐(3‐Aryl‐1‐hydroxy‐2‐methylprop‐2‐enyl)‐1,4‐benzodiazepin‐2‐ones
Authors: Hameršak Zdenko , Gašo Dajana , Kovač Spomenka , Hergold‐Brundić Antonija , Vicković Ivan , Šunjić Vitomir
Published: July 2003

Aldol reaction of 7‐chloro‐1,3‐dihydro‐1‐methyl‐5‐phenyl‐2H‐1,4‐benzodiazepin‐2‐one (1) with 4‐substituted α‐methylcinnamaldehydes 2–5 afforded a mixture of threo‐ and erythro‐3‐(3‐aryl‐1‐hydroxy‐2‐methylprop‐2‐enyl)‐7‐chloro‐1,3‐dihydro‐1‐methyl‐5‐phenyl‐2H‐1,4‐benzodiazepin‐2‐ones 6–13. The chromatographically separated threo diastereoisomers 6, 8, 10, and 12 and erythro diastereoisomers 7, 9, 11, and 13 were submitted to ‘directed' homogeneous hydrogenation catalyzed by [RhI(cod)(diphos‐4)]ClO4 (cod=cycloocta‐1,5‐diene, diphos‐4=butane‐1,4‐diylbis[diphenylphosphine]. From the erythro‐racemates 9, 11, and 13, the erythro,erythro/erythro,threo‐diastereoisomer mixtures 16/17, 20/21, and 24/25 were obtained in ratios of 20 : 80 to 28 : 72 (HPLC), which were separated by chromatography. From the threo racemates 8, 10, and 12, the threo,threo/threo,erythro‐diastereoisomer mixtures were obtained in a ratio of ca. 25 : 75 (1H‐NMR). The relative configurations were assigned by means of 1H‐NMR data and X‐ray crystal‐structure determination of 21. Hydrolysis of 21 afforded the diastereoisomerically pure N‐(benzyloxy)carbonyl derivative 27 of α‐amino‐β‐hydroxy‐γ‐methylpentanoic acid 26, representative of the novel group of polysubstituted α‐amino‐β‐hydroxycarboxylic acids.
Regio‐ and Stereoselectivity of the SiO2‐Catalyzed Reaction of Thiocamphor (=1,7,7‐Trimethylbicyclo[2.2.1]heptane‐2‐thione) with Optically Active Monosubstituted Oxiranes
Authors: Fu Changchun , Linden Anthony , Heimgartner Heinz
Published: July 2003

The reactions of the enolizable thioketone (1R,4R)‐thiocamphor (=(1R,4R)‐1,7,7‐trimethylbicyclo[2.2.1]heptane‐2‐thione; 1) with (S)‐2‐methyloxirane (2) in the presence of a Lewis acid such as SnCl4 or SiO2 in anhydrous CH2Cl2 led to two diastereoisomeric spirocyclic 1,3‐oxathiolanes 3 and 4 with the Me group at C(5′), as well as the isomeric β‐hydroxy thioether 5 (Scheme 2). The analogous reactions of 1 with (RS)‐, (R)‐, and (S)‐2‐phenyloxirane (7) yielded two isomeric spirocyclic 1,3‐oxathiolanes 8 and 9 with Ph at C(4′), an additional isomer 13 bearing the Ph group at C(5′), and three isomeric β‐hydroxy thioethers 10, 11, and 12 (Scheme 4). In the presence of HCl, the β‐hydroxy thioethers 5, 10, 11, and 12 isomerized to the corresponding 1,3‐oxathiolanes 3 and 4 (Scheme 3), and 8, 9, and 13, respectively (Scheme 5). Under similar conditions, an epimerization of 3, 8, and 9 occurred to yield the corresponding diastereoisomers 4, 14, and 15, respectively (Schemes 3 and 6). The structures of 9 and 15 were confirmed by X‐ray crystallography (Figs. 1 and 2). These results show that the Lewis acid‐catalyzed addition of oxiranes to enolizable thioketones proceeds with high regio‐ and stereoselectivity via an Sn2‐type mechanism.
Reactions of Stable α‐Chlorosulfanyl Chlorides with CS‐Functionalized Compounds
Authors: Majchrzak Agnieszka , Janczak Aleksandra , Mlostoń Grzegorz , Linden Anthony , Heimgartner Heinz
Published: July 2003

The smooth reaction of 3‐chloro‐3‐(chlorosulfanyl)‐2,2,4,4‐tetramethylcyclobutanone (3) with 3,4,5‐trisubstituted 2,3‐dihydro‐1H‐imidazole‐2‐thiones 8 and 2‐thiouracil (10) in CH2Cl2/Et3N at room temperature yielded the corresponding disulfanes 9 and 11 (Scheme 2), respectively, via a nucleophilic substitution of Cl− of the sulfanyl chloride by the S‐atom of the heterocyclic thione. The analogous reaction of 3‐cyclohexyl‐2,3‐dihydro‐4,5‐diphenyl‐1H‐imidazole‐2‐thione (8b) and 10 with the chlorodisulfanyl derivative 16 led to the corresponding trisulfanes 17 and 18 (Scheme 4), respectively. On the other hand, the reaction of 3 and 4,4‐dimethyl‐2‐phenyl‐1,3‐thiazole‐5(4H)‐thione (12) in CH2Cl2 gave only 4,4‐dimethyl‐2‐phenyl‐1,3‐thiazol‐5(4H)‐one (13) and the trithioorthoester derivative 14, a bis‐disulfane, in low yield (Scheme 3). At −78°, only bis(1‐chloro‐2,2,4,4‐tetramethyl‐3‐oxocyclobutyl)polysulfanes 15 were formed. Even at −78°, a 1 : 2 mixture of 12 and 16 in CH2Cl2 reacted to give 13 and the symmetrical pentasulfane 19 in good yield (Scheme 5). The structures of 11, 14, 17, and 18 have been established by X‐ray crystallography.
Habitat Structure and Trichoptera Diversity in Two Headwater Flood Plains, N.E. Italy
Authors: Arscott Dave B. , Keller Barbara , Tockner Klement , Ward J. V.
Published: July 2003

Two headwater flood plains in tributaries of the Tagliamento catchment (N.E. Italy) were investigated to compare and contrast floodplain morphology, aquatic habitat structure, physico‐chemical characteristics, and Trichoptera community relationships. The two flood plains (one stable and forested, the other dynamic and open) were similar with respect to position along the longitudinal continuum, elevation, stream order, and geological material. However, the two flood plains differed greatly in aquatic habitat structure, physico‐chemical character, and Trichoptera abundance, distribution, and richness. The forested reach had lower slope, finer sediment, more standing waterbodies, significantly higher benthic organic matter standing stocks, and a closed canopy of predominantly Alnus incana. Trichoptera abundance in the forested flood plain was higher, as was taxa richness (27 taxa), than in the open flood plain (16 taxa). Differences in Trichoptera composition and richness were due to the presence of several species of Limnephilidae, which were correlated with benthic organic matter. These findings are discussed in the context of species‐abundance relationships, environmental factors, and reach‐specific morphological characters. Results illustrate the dependence of habitat type and invertebrate community response to reach scale factors (i.e., geomorphology and hydrology) that may be uncoupled from position along the longitudinal continuum.
Processes of Surface‐Subsurface Water Exchange in a Low Energy Sand‐Bed Stream
Authors: Mutz Michael , Rohde Anja
Published: July 2003

The surface‐subsurface water exchange at base‐flow conditions was assessed in a natural sand‐bed stream. The aim was to examine the relative contribution of sediment turnover and vertical hyporheic flow in a natural environment. Sediment turnover was determined using coloured sand columns implanted into the stream bed. Direction and velocity of hyporheic flow was recorded with a fluid tracer injected into the stream bed. Large amounts of wood caused a heterogeneous stream bed relief. Grain size distribution of sediments was homogenous with a porosity of 37%. The hydraulic conductivity ranged from 3 · 10−6 m s−1 to 1 · 10−4 m s−1 with a mean of 7 · 10−5 m s−1. Groundwater upwelling was a major process (0.39 l m−2 h−1) and stream water was passing through the hyporheic zone at a rate of 0.12 l m−2 h−1. Since hyporheic velocity was high in comparison to flume studies, the transfer of stream water through bed sediments might have been induced by the wood in addition to local topography in the sand‐bed. Sediment displacement at base‐flow was found in 79% of the stream bed. Release and trapping of pore water by sediment turnover contributed greatly to the surface‐subsurface water exchange. Pumping and sediment turnover were significant processes of the vertical connectivity in the natural sand‐bed stream.
Dietary and Stable Isotope (δ 13C, δ 15N) Analyses in Alpine Stream Insects
Authors: Füreder Leopold , Welter Camille , Jackson John K.
Published: July 2003

Alpine stream systems are known to be affected by the prevailing water sources (glacial, non‐glacial), regional climate and the vegetation of the watershed. Especially at higher altitudes, these conditions influence and shape abiotic factors and the biology of stream reaches, there usually resulting in harsh environmental settings for the biota. Little is known about nutrients, food availability and food utilization in these systems. We investigated the physico‐chemical conditions, food resources (DOM, CPOM, FPOM, seston, Aufwuchs) and the bottom fauna in nine reaches of different stream types (glacial, non‐glacial systems) above and below the treeline in two seasons. Gut content and stable isotope (δ 15N, δ 13C) analysis were used to estimate food consumption and assimilation for dominant species. Although most of the taxa were detritivores, some species showed a preference for specific food items. Both, the principal dietary component as well as stable isotope analyses confirmed the placement of taxa into functional feeding guilds. In addition the results of stable isotope analysis suggested opportunistic feeding of several species. Autochthony appeared to play an important role even in glacial streams, where long snow cover, frequent flooding and high turbidity limit Aufwuchs development for most months of the year.
Structure and Functional Organization of Benthic Invertebrates in a Regulated Stream
Authors: Fleituch Tadeusz
Published: July 2003

This paper examines modifications of benthic structure and species/traits organization of macroinvertebrate communities affected by various hydro‐technical structures in the regulated mountain Trzemesnia stream (southern Poland). The samples of aquatic invertebrates were collected seasonally (6 times) at: (1) one control site with natural substrate and at (2) five sites altered by sills, weirs, and canals during 1999.

The stream canals, covered by Cladophora glomerata, were clearly distinguished from the other sites by: highest fauna density (mean of 8.5 103 ind. m−2), lowest taxa richness (mean number of 4.7 taxa), and lowest diversity (H′ = 1.1). The benthic communities consisted mainly of collector‐gatherers with the highest contribution in the stream canals (range 87–96%). These results suggest that most types of stream regulations (i.e. stream bed formed by concrete bricks) negatively affect the functional organization of benthic invertebrates (collector‐gatherers, predators, and scrapers).
A Study of Biofilm in a Second Order Tropical Stream, Njoro River, Kenya: First Results
Authors: Muia Wairimu A. , Bretschko Gernot , Herndl Gerhard J.
Published: July 2003

Between January and December 1999 the extent of biofilm development has been studied at two sites (muddy sediment site [A] and sandy sediment site [B]) in Njoro River, Kenya. Grain size, organic matter and bacterial abundance were determined at different depth layers of the sediment. Particulate carbohydrate concentrations were measured as an indicator of biofilm development in the sediment. Additionally, the development of the biofilm was investigated by placing glass slides at rock and sediment surfaces and in different sediment depth layers. Our first results for sediment samples collected in January 1999 and growth on slides exposed for 28 days in March 1999 is presented. Grain size analysis revealed that sediment particles <1 mm contributed between 82 to 91% at site A and 45 to 67% at site B depending on the sediment layer. At site A, total organic matter (% weight loss on ignition) and total organic carbon (TOC) were more or less constant with depth while both parameters significantly decreased with depth at site B. Total organic nitrogen (TON) was detectable at all depth layers at site A but only in the top 40 mm layer at site B. Bacterial numbers were highest in the top 40 mm layer at both sites. Bacterial abundance of 3.95 ± 5.96 × 108 and 4.10 ± 3.88 × 108 cells g−1 dry sediment were recorded at site A and B, respectively. For both sites, highest concentrations of colloidal carbohydrates occurred in the top 40 mm layer, but concentrations were more or less constant below. Bacterial abundance on glass slides was higher on slides placed on rock surfaces than on fine sediment surfaces or within fine sediments.
Effect of sphered particles on the firing contraction of porcelain inlay processed by cold isostatic pressing
Authors: Konishi Junko , Watari Fumio , Kawamoto Chiharu , Sano Hidehiko
Published: July 2003

The effect of the sphered particles on the contraction ratio of porcelain inlay processed by the cold isostatic pressure (CIP) method was investigated. The conventional lathe‐cut porcelain powder was crushed to finer particles and the secondary particles with spherical shape by adding binders of acrylic resin, wax, and polyvinyl alcohol, respectively. Porcelain powder was molded as a disc‐shaped green body in a refractory model and compressed at 200 MPa by CIP. From this green compact, the sintered porcelain was obtained by only one step of firing. The porcelain discs were then used for the measurements of contraction ratio, scanning microscopic observation, biaxial flexure strength, Vickers hardness, and density. Firing contraction was decreased to about 1% in the sphered particle groups, compared with 7% of the lathe‐cut porcelain powder. Although biaxial flexure strength was about 85 MPa, which is lower than the 120 MPa of the control group, and the density was significantly decreased by about 10% from the 2.4 g/cm3 of the control substance, Vickers hardness, which ranged from 531 to 537, showed no significant differences among all of the groups. The CIP method could save labor in the process of making porcelain inlays, and sphered powders could contribute significantly to a decrease in the contraction ratio in the sintering process. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 66B: 553–558, 2003
Long‐term study of high‐strength hydroxyapatite/poly(L‐lactide) composite rods for the internal fixation of bone fractures: A 2–4‐year follow‐up study in rabbits
Authors: Ishii Shinsuke , Tamura Jiro , Furukawa Taizo , Nakamura Takashi , Matsusue Yoshitaka , Shikinami Yasuo , Okuno Masaki
Published: July 2003

Biodegradation of hydroxyapatite (HA)/poly(L‐lactide)(PLLA) composite bone implant rods was studied with the use of two types of HA particles as reinforcing fillers: uncalcined HA (u‐HA) or calcined HA (c‐HA). Composite rods of u‐HA/PLLA and c‐HA/PLLA containing 30 or 40% (w/w) HA were implanted in the distal femur of 21 rabbits, and specimens were examined by light microscopy, scanning‐electron microscopy (SEM), and transmission‐electron microscopy (TEM) 2–4 years later. For u‐HA/PLLA, trabecular bone bonding directly onto the rod was maintained for up to 2 years. By 3 years, surface collapse had begun, and the implants were shrinking. By 4 years, they had shrunk further, with complete bone encapsulation. The u‐HA particles were small and needle shaped in the peripheries, and TEM confirmed their resorption. The cross‐sectional area after 4 years decreased by 23.3 ± 8.4%. The mean ratio of bony ingrowth to the initial cross‐sectional area around the shrunken rods was 6.7 ± 1.3 %. The viscosity molecular weight of PLLA reduced from 2 × 105 to less than 1 × 103. Thus, most of the PLLA had released from the rods. The c‐HA/PLLA implants also showed good osteoconductivity, but shrinkage and infiltration of histiocytes were less. No osteolytic or osteoarthritic changes were found. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 66B: 539–547, 2003
Residual ethylene oxide in medical devices and device material
Authors: Lucas Anne D. , Merritt Katharine , Hitchins Victoria M. , Woods Terry O. , McNamee Scott G. , Lyle Dan B. , Brown Stanley A.
Published: July 2003

Ethylene oxide (EO) gas is commonly used to sterilize medical devices. The amount of residual EO remaining in a device depends partly on the type and size of polymeric material. A major concern is the amount of residue that may be available in the body. With the use of the method described by AAMI for headspace analysis of EO residues, different polymers and medical devices subjected to different numbers of sterilization cycles were examined. Next, the effect of various extraction conditions and extraction solutions on these polymers and medical devices was evaluated. The results showed different polymers desorb EO differently. One polyurethane (PU 75D) had much higher EO residue than a different polyurethane (PU 80A). Repeated extraction of the PU 75D was necessary to quantify total EO residue levels. Different extraction solutions influence the amount and reproducibility of EO detected, whereas multiple resterilizations showed no difference in amount of residual EO. Bioavailability of EO was estimated by extracting the devices and polymers in water. Comparison of total EO residues to EO that was bioavailable showed no difference for some polymers and devices, while others had an almost eightfold difference. Some standard biocompatibility tests were run on extracts and devices, but no significant effects were observed. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 66B: 548–552, 2003
In vivo efficacy of bone‐marrow‐coated polycaprolactone scaffolds for the reconstruction of orbital defects in the pig
Authors: Rohner Dennis , Hutmacher Dietmar W. , Cheng Tan Kim , Oberholzer Martin , Hammer Beat
Published: July 2003

Alloplastic materials offer a number of advantages over bone autografts in the reconstruction of craniofacial defects. These include: lack of donor site morbidity, unlimited quantities of available material, and the possibility to conform exactly to the defect. An ideal bioresorbable material would degrade slowly, and have osteoconductive properties to allow replacement and remodeling by osseous tissue. This is seldom observed, the materials instead being replaced by fibrous tissue. Polycaprolactone (PCL), an FDA‐approved bioresorbable polymer, has several properties that might make it suitable for reconstruction of craniofacial defects. The technique of fused deposition modeling (FDM) allows for the fabrication of highly reproducible bioresorbable 3D scaffolds. The nature of the fully interconnected pore network might enhance vascular ingrowth and osteoconductive properties. It was hypothesized that coating the scaffolds in bone marrow might enhance bone formation due to the osteoinductive nature of the bone‐marrow mesenchymal cells. This study aimed to test these hypotheses in the pig model. Defects measuring 2 × 2 cm were surgically created in each orbit of eight Yorkshire pigs. The orbits were divided into three groups: Group 1 (n = 4), no reconstruction (control); Group 2 (n = 6), reconstruction with no coated PCL scaffolds; and Group 3 (n = 6) reconstruction with bone‐marrow‐coated PCL scaffolds. The results were evaluated at 3 months by histological and histomorphometric analyses. The defects in Group 1 were covered with fibrous scar tissue. The shape of the reconstructed area was insufficient. The defects in Groups 2 and 3 were reconstructed correctly. In Group 2 the noncoated scaffolds showed 4.5% of new bone formation compared with 14.1% in Group 3, which is statistically significant (p < 0.05). The entirely interconnected 3D polycaprolactone scaffold seems to be a promising material. It induces the bone ingrowth required for reconstructing craniofacial and orbital defects. Further long‐term evaluations of these PCL scaffolds must be made in order to confirm these conclusions. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 66B: 574–580, 2003
Evaluation of a new CPC‐to‐gauge bonding technique with the use of in vitro fluid flow
Authors: Fernandez Mark M. , Szivek John A. , Margolis David S.
Published: July 2003

Strain gauging enables the measurement of bone deformation during physical activity, leading to a better understanding of the physiological effects of loading on bone growth and remodeling. Development of a technology that will withstand long‐term in vivo exposure and bond securely to bone is imperative for accurate, consistent measurement collection. Polysulfone is currently used to attach calcium‐phosphate ceramic (CPC) particles, which promote bone‐to‐gauge bonding, to polyimide‐backed strain gauges. This study evaluated the use of an implant‐grade epoxy as an alternative CPC–polyimide adhesive. Polyimide–epoxy–CPC interfaces were loaded to failure and shear strengths calculated. In vitro studies providing a constant flow of medium over test specimens were designed, and long‐term in vitro fluid exposure studies of the epoxy's shear strength were conducted. Average shear strength of polysulfone‐polyimide interfaces were reported to be 7 MPa.11 The average shear strength of the epoxy‐polyimide interface before long‐term in vitro exposure was 17 MPa, which is stronger than the shear strength of the bone–CPC interface.12 The strength of the epoxy–polyimide interface decreased to 6.8 MPa after 24 weeks in vitro and 3 MPa after 24 weeks in vivo. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 66B: 514–519, 2003
Adsorption of catechol and comparative solutes on hydroxyapatite
Authors: Chirdon William M. , O'Brien William J. , Robertson Richard E.
Published: July 2003

Contemporary medical and dental adhesives often have difficulty sticking to wet surfaces or weaken with long‐term exposure to water. Substantial research has been dedicated to finding a means of achieving adhesion in an aqueous environment. A study evaluates the adsorption of catechol relative to other chemical groups as means of gauging how effective they may be as adsorptive groups in adhesives. Contact angle and surface‐tension measurements of solutions of catechols and other chemical groups were used to determine their works of adhesion. Adsorption isotherms were also constructed to ascertain Langmuir constants. Solutes containing catechol groups were compared to solutes containing other polar groups to see how well catechol adsorbs to hydroxyapatite, the mineral component of bones and teeth, relative to other chemical groups found in adhesives. The results of this study show that catechol and molecules containing catechol groups have higher rates and energies of adsorption to hydroxyapatite than do groups such as alcohols, amines, and carboxylic acids. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 66B: 532–538, 2003
In vivo histological response to anodized and anodized/hydrothermally treated titanium implants
Authors: Son Won‐woo , Zhu Xiaolong , Shin Hong‐in , Ong Joo L. , Kim Kyo‐han
Published: July 2003

In the study, characterization of the anodized titanium surface was performed. In addition, histological evaluation and interfacial strength at the bone–implant interface of the characterized surfaces were then evaluated with the use of a rabbit model at 6 and 12 weeks after implantation. Surface treatments consisted of either anodization or anodization followed by hydrothermal treatments. Nontreated titanium surfaces were used as controls in this study. Using scanning‐electron microscopy, porous oxide layers were observed on surfaces of anodized titanium implants, whereas porous oxide layers and HA needles were observed on anodized titanium implants following hydrothermal treatments. X‐ray diffraction analysis showed the oxide layers were consisted mainly of anatase and a little of rutile. By the hydrothermal treatment on the anodizing surface, HA peaks, as well as the peaks of anatase and trace amounts of rutile peaks were observed. In EPMA analysis, the Ca/P ratio for the anodic oxide was 1.54 for anodized surfaces, whereas the Ca/P ratios for HA needles and the anodic oxide were 1.64 and 0.57, respectively, for anodized surfaces following hydrothermal treatments. Although no significant difference was observed for the percent bone contact on all implants evaluated in the in vivo study, the removal torque strength was significantly higher for anodized implants (48.02 ± 5.92 N/cm) than the untreated implants (controls) (27.83 ± 1.78 N/cm) at 6 weeks after implantation. As such, it was concluded that the surface anodized implants resulted in a high interfacial strength at an early implantation period as compared to the nontreated titanium implants. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 66B: 520–525, 2003
Use of isothermal heat‐conduction microcalorimetry (IHCMC) for the evaluation of synthetic biomaterials
Authors: Lewis Gladius , (Dan) Daniels A. U.
Published: July 2003

Isothermal heat‐conduction microcalorimetry (IHCMC) allows measurement of extremely small rates of heat flow—on the order of 0.1 microwatt. This provides, for example, the ability to directly observe—and quantitate in a few days—rates of degradation as low as 1% per year at body temperature, in solid material samples of a few grams. Also, one method of IHCMC data analysis allows direct determination of the reaction‐rate constant at the temperature of interest, thereby avoiding possible errors due to rate mechanism changes with temperature, an issue that needs to be considered when the Arrhenius method is used. IHCMC can also be used to measure transient phenomena, such as heat of adsorption, and initial metabolic responses of cellular entities to biomaterials. The purposes of this review article are to (a) explain the basic principles, attractive features, limitations, and methods of IHCMC; (b) describe biomaterials applications to date—including studies of the stability of ultra‐high‐molecular‐weight polyethylene and implant‐grade calcium sulfate, setting reactions of dental adhesives, and macrophage response to biomaterial particles; (c) provide a discussion of issues and concerns that should be addressed in order to maximize the utility of IHCMC in biomaterials studies; and (d) suggest a number of possible future biomaterials applications for this technique. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 66B: 487–501, 2003
The preparation of monodisperse biodegradable polyester nanoparticles with a controlled size
Authors: Zweers Miechel L.T. , Grijpma Dirk W. , Engbers Gerard H.M. , Feijen Jan
Published: July 2003

In local drug delivery, nanoparticles based on biodegradable polymers can function as vehicles with controlled drug‐release properties. To achieve a well‐controlled drug‐release profile, control over the particle size is of great importance. Therefore, biodegradable polyester nanoparticles were prepared by the salting‐out method. Process variables were varied to study the effect on the particle size. The monodisperse particles obtained were between 100 and 400 nm in size and spherical in shape. It was found that the particle size could be adjusted by varying the preparation conditions upon which the polymer concentration had the most pronounced effect. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 66B: 559–566, 2003
Synthesis of 4‐[18F]fluoroiodobenzene and its application in sonogashira cross‐coupling reactions
Authors: Wüst Frank R. , Kniess Torsten
Published: July 2003

The first application of a Sonogashira cross‐coupling reaction in 18F chemistry has been developed. The reaction was exemplified by the cross‐coupling of terminal alkynes (ethynylcyclopentyl carbinol 6, 17α‐ethynyl‐3,17β‐estradiol 7 and 17α‐ethynyl‐3‐methoxy‐3,17β‐estradiol 8) with 4‐[18F]fluoroiodobenzene. 4,4′‐Diiododiaryliodonium salts were used as precursors for the synthesis of 4‐[18F]fluoroiodobenzene, enabling the convenient access to 4‐[18F]fluoroiodobenzene in 13–70% yield using conventional heating or microwave activation. The Sonogashira cross‐coupling of 4‐[18F]fluoroiodobenzene with terminal alkynes gave the corresponding 4‐[18F]fluorophenylethynyl‐substituted compounds [18F]‐9, [18F]‐10 and [18F]‐13 in yields up to 88% within 20 min of starting from 4‐[18F]fluoroiodobenzene. Copyright © 2003 John Wiley & Sons, Ltd.
125I‐Labeled 2‐O‐ and 3‐O‐m‐iodobenzyl, and 6‐O‐m‐iodophenyl derivatives of L‐ascorbic acid: synthesis and preliminary tissue distribution
Authors: Yamamoto Fumihiko , Kuwano Eri , Kaneshiro Tetsuo , Sasaki Shigeki , Maeda Minoru
Published: July 2003

Three 125I‐labeled 2‐O‐ and 3‐O‐m‐iodobenzyl, and 6‐O‐m‐iodophenyl derivatives of L‐ascorbic acid were prepared by melt exchange procedures in isolated radiochemical yields of 12–60% after HPLC purification. Biodistribution studies in tumor‐bearing mice showed very different in vivo tissue uptake properties from previous results obtained with 14C‐labeled ascorbic acid and 6‐deoxy‐6‐[18F]fluoro‐L‐ascorbic acid. None of these seems to be suitable radioiodinated analogs of L‐ascorbic acid for imaging study of its in vivo biochemistry. Copyright © 2003 John Wiley & Sons, Ltd.
Preparation and biological evaluation of 99mTc‐stannous fluoride colloid‐labelled‐leucocytes in rats 99mTc‐stannous fluoride‐labelled‐leucocytes in rats
Authors: Tsopelas C. , Smith E. , Drew P.A. , Bartholomeusz F.D.L.
Published: July 2003

High splenic activity is always visible in 99mTc‐stannous fluoride (SnF2)‐labelled‐leucocytes scans. In an attempt to reduce this activity, this study investigated the effect of pre‐injected SnF2 colloid on the distribution of 99mTc‐SnF2 colloid, 99mTc‐SnF2‐labelled‐leucocytes, and opsonized 99mTc‐SnF2 colloid in rats. The radiopharmaceuticals 99mTc‐SnF2 colloid and 99mTc‐SnF2‐leucocytes were each found to exhibit identical biodistributions in separate experiments. SnF2 colloid pre‐injection (26 μg) resulted in reduced splenic uptake of 99mTc‐SnF2 colloid (38%) and 99mTc‐SnF2‐labelled‐leucocytes (30%), but not for opsonized 99mTc‐SnF2 colloid. This indicates that the level of opsonization of radiocolloid is rate limiting rather than the phagocytic capacity of liver and spleen macrophages. There is a low level of 99mTc‐SnF2‐labelled‐leucocytes dominated by unopsonized radiocolloid in the ex vivo whole blood dose. Following administration of this dose, free radiocolloid is present in vivo that predominantly localizes in the liver and spleen. This uptake can be challenged with non‐radioactive stannous fluoride colloid pre‐injection, where splenic activity can be significantly reduced by up to 52%. Copyright © 2003 John Wiley & Sons, Ltd.
Redefining the climate zones of Turkey using cluster analysis
Authors: Unal Yurdanur , Kindap Tayfun , Karaca Mehmet
Published: July 2003

Climate zones of Turkey are redefined by using the mathematical methodology of cluster analysis. Data from 113 climate stations for temperatures (mean, maximum and minimum) and total precipitation from 1951 to 1998 are used after standardizing with zero mean and unit variance, to confirm that all variables are weighted equally in the cluster analysis. Hierarchical cluster analysis is chosen to perform the regionalization. Five different techniques were applied initially to decide the most suitable method for the region. Stability of the clusters is also tested. It is decided that Ward's method is the most likely to yield acceptable results in this particular case, as is often the case in climatological research. Seven different climate zones are found, as in conventional climate zones, but with considerable differences at the boundaries. Copyright © 2003 Royal Meteorological Society
Comparison of techniques for detection of discontinuities in temperature series
Authors: Ducré‐Robitaille Jean‐François , Vincent Lucie A. , Boulet Gilles
Published: July 2003

Several techniques for the detection of discontinuities in temperature series are evaluated. Eight homogenization techniques were compared using simulated datasets reproducing a vast range of possible situations. The simulated data represent homogeneous series and series having one or more steps. Although the majority of the techniques considered in this study perform very well, two methods seem to work slightly better than the others: the standard normal homogeneity test without trend, and the multiple linear regression technique. Both methods are distinctive because of their sensitivity concerning homogeneous series and their ability to detect one or several steps properly within an inhomogeneous series. Copyright © 2003 Environment Canada. Published by John Wiley & Sons, Ltd.
Frequency of Bay of Bengal cyclonic storms and depressions crossing different coastal zones
Authors: Alam Md. Mahbub , Hossain Md. Arif , Shafee Sultana
Published: July 2003

All the storms and depressions that formed in the Bay of Bengal during 1974–99 have been analysed. The number of occurrences in July is not in harmony with that of other months of the monsoon. Regions stricken are taken into account on a monthly, seasonal and annual basis. The Indian coast faces almost an equal number of storms and depressions that are formed from June to November. The most vulnerable months for storms are May, October and November for Bangladesh; May for Myanmar; June, August and September for Kolkata–Vishakhapatnam in India and October and November for Vishakhapatnam–Tamilnadu in India. Most of the monsoon depressions cross the Kolkata–Vishakhapatnam coast of India. The frequency of formation has been observed to decrease during the period of analysis. It is also observed that the frequency distribution of the Bay of Bengal storms has two peaks: one in the month of May and the other in the month of November. Copyright © 2003 Royal Meteorological Society
The influence of natural conditions on the spatial variation of climate in Lapland, northern Finland
Authors: Vajda Andrea , Venäläinen Ari
Published: July 2003

At high latitudes in Lapland, near the climatological timberline, forestry and other environmental research require detailed information about the spatial variation of climate. In this study, the influence of local geographical factors on the climate in northern Finland (Lapland), as well as the applicability of the kriging interpolation method in the case of detailed spatial resolution, were examined. The spatial analysis of mean, maximum, minimum temperatures, length of the frost‐free season, degree‐days and daily range was made using a 1 km × 1 km resolution. The time period used was 1971–2000. We studied whether taking account of external forcing, such as lake coverage and altitude, would improve the accuracy of spatial interpolation of climatological parameters. The geographical factors of coordinates, elevation, lakes and sea influence on the regional features of the climate were examined. According to the results of this study, only geographical position and local relief have a significant influence on regional climate in Lapland. The effect of lakes and sea seems to be secondary. Copyright © 2003 Royal Meteorological Society
Variability of extreme temperature events in south–central Europe during the 20th century and its relationship with large‐scale circulation
Authors: Domonkos Peter , Kyselý Jan , Piotrowicz Katarzyna , Petrovic Predrag , Likso Tanja
Published: July 2003

The variability of winter extreme low‐temperature events and summer extreme high‐temperature events was investigated using daily temperature series (1901–98) from 11 sites in central and southern Europe. An extreme temperature event (EXTE) is defined by various threshold values of daily temperature or daily temperature anomaly. Systematic changes in the frequencies of EXTEs are investigated by the Mann–Kendall test and a method based on the Wilcoxon test. The catalogue of macrocirculation types over central Europe (the Hess–Brezowsky classification) is applied to investigate the connections between EXTEs and large‐scale circulation. Circulation classes (HBC) are defined, and mostly spatial averages of EXTEs are examined.

There were large long‐term fluctuations in the frequencies of both winter extreme cold events (EXCEs) and summer extreme warm events (EXWEs) during the 20th century. The systematic changes referring to the entire period indicate a slight warming tendency, but only a few of the changes, mostly in the northernmost sites, are statistically significant. Strong connections are present between the frequencies of EXTEs and the large‐scale circulation on various time scales, particularly for EXCEs. The spatial differences of EXTE fluctuations and EXTE–HBC connections are small within the study area. Northerlies and easterlies, as well as meridional and anticyclonic situations, are favourable for EXCEs, whereas southerlies and persistent anticyclonic situations are favourable for EXWE occurrences. In the latest decades, a decline in the frequency of EXCEs and a sharp increase in the frequency of EXWEs happened, and the residence times of the circulation patterns over central Europe became longer both in winter and summer. Copyright © 2003 Royal Meteorological Society