bluuebunny/crossref_metadata_2025 huggingface dataset:
Electrophilic Bromination of N‐Acylated Cyclohex‐3‐en‐1‐amines: Synthesis of 7‐Azanorbornanes
Authors: Kapferer Peter , Vasella Andrea
Published: November 2004

The intramolecular bromo‐amidation and the dibromination‐cyclisation of the N‐acylcyclohex‐3‐en‐1‐amines 4, 8, 9, 11, 13, 14, and 16 was studied in view of the synthesis of bicyclic amines that are of interest as building blocks and potential glycosidase inhibitors. The trifluoroacetamides 4, 9, and 14 reacted with N‐bromosuccinimide (NBS) in AcOH to give dihydro‐1,3‐oxazines in good yields. The stereoselectivity of the dibromination of the alkenes 8 and 9 depends on the nature of the protecting group, the reagent, and the reaction conditions. Br2 in CH2Cl2 transformed the alkenes 8 and 9 predominantly into diaxial trans,trans‐dibromides. Bromination of 9 with PhMe3NBr3 or with Br2 in the presence of Et4NBr gave predominantly the diequatorial trans,cis‐27 besides some trans,trans‐28. A similar bromination of the C(5)‐substituted N‐acyl‐4‐aminocyclohexenes 11, 13, 14, and 16 with PhMe3NBr3 was accompanied by intramolecular side reactions that were suppressed by the addition of excess Et4NBr. Under these conditions, 11 gave diastereoselectively trans‐dibromides, while its reaction with Br2 gave trans‐dibromides along with the dihydrooxazinone 31. Also the carbamate 13 reacted with PhMe3NBr3/Et4NBr selectively to the trans‐dibromide 32 and with Br2 to the trans‐dibromides 32 and 33, the dihydrooxazinone 34, and the bicyclic ether 35. Similarly, the trifluoroacetamide 14 provided the dibromide 36 (89%), while its reaction with Br2 led to the dihydrooxazine 22, and the dibromides 36 and 37. The N‐benzyl‐N‐Boc derivative 16 did not yield any dibromide; it reacted with PhMe3NBr3/Et4NBr to the dihydrooxazinone 38, and with Br2 to the oxazinone 38 and the bicyclic ether 39. The high stereoselectivity of the bromination with PhMe3NBr3/Et4NBr suggests an anchimeric assistance of the NHR substituent. Deprotection, cyclisation, and carbamoylation transformed the dibromides 27, 29, and 32 into the 7‐azanorbornanes 42, 49, and 53. The diols 45 and 57 were obtained from 42 and 53 via HBr elimination and stereoselective dihydroxylation; they proved weak inhibitors of several glycosidases. In no case could the formation of a bicyclic azetidine (6‐azabicyclo[3.1.1]heptane) from the dibromides 26 and 30 be observed.
Nonnucleosidic Base Surrogates: The Effect of 1,2‐Disubstituted Phenanthrenes on DNA Duplex Stability
Authors: Ackermann Damian , Häner Robert
Published: November 2004

Phenanthrene‐1,2‐dimethanol was incorporated into oligodeoxynucleotides via formation of phosphodiester bonds (cf. Scheme 1). If placed at internal positions in a DNA duplex, a strong reduction of duplex stability is observed (Table 1). Terminal attachment of stretches of phenanthrene residues, however, leads to a substantial increase in stability. The stabilization is attributed to a cooperative interaction of the phenanthrene residues of the two strands rather than to dangling end effects. Chimeric oligomers containing a stretch of six phenanthrene residues show two separate transitions (Table 2): one arising from the denaturation of the DNA stem (observable by a hyperchromic effect at 260 nm) and a second one from the denaturation of the phenanthrene part (observable by temperature‐dependant gel mobility assays). Based on these findings, a model of the chimeric hybrids is proposed, in which the phenanthrene residues stack in a zipper‐like manner on top of the DNA base pairs without disrupting the B‐form of the DNA stem (see Fig. 7).
Efficient Solid Phase Synthesis of Cleavable Oligodeoxynucleotides Based on a Novel Strategy for the Synthesis of 5′‐S‐(4,4′‐Dimethoxytrityl)‐2′‐deoxy‐5′‐thionucleoside Phosphoramidites
Authors: Jahn‐Hofmann Kerstin , Engels Joachim W.
Published: November 2004

The incorporation of a specific cleavage site into an oligodeoxynucleotide can be achieved by utilizing the four 5′‐S‐(4,4′‐dimethoxytrityl)‐2′‐deoxy‐5′‐thionucleoside 3′‐(2‐cyanoethyl diisopropylphosphoramidites) 5 and 15a–c (Fig. 1). Based on the silver ion assisted cleavage of PS and CS bonds, we synthesized oligodeoxynucleotides with an achiral 5′‐phosphorothioate linkage 3′–O–P–S–5′ by the solid‐phase phosphoramidite procedure. The efficient cleavage of these modified oligodeoxynucleotides can be detected by HPLC, PAGE, and surface plasmon resonance (SPR) spectrometry. The liberated 5′‐thiol moiety can be used directly for post‐reaction labeling with appropriately functionalized reporter groups.
Novel Bleomycin Analogues: Synthesis, Antitumor Activity, and Interaction with DNA
Authors: Xu Zhi‐Dong , Wang Min , Xiao Su‐Long , Zhang Yan‐Juan , Yang Ming
Published: November 2004

The novel analogues 11–16 of bleomycin A6 (3) were obtained by selective protection of the primary‐amine function of the β‐aminoalaninamide moiety of 3 by means of coordination with CuII ions, condensation with an aliphatic or aromatic acid R′COOH in the presence of dicyclohexylcarbodiimide, and demetalization (Scheme). The antitumor activity against HeLa and BGC‐823 in vitro, binding property with CT‐DNA, and cleavage potency towards pBR322 DNA were also studied (Tables 1–3). All the compounds 11–16 displayed significant antitumor activity, which was enhanced as the hydrophobicity of the C‐terminus substituent R′ increased, but decreased as the DNA‐binding affinity increased. There was a negative relationship between DNA‐cleavage potency and binding affinity to DNA in this series of compounds.
Rubriflorin A and B, Two Novel Partially Saturated Dibenzocyclooctene Lignans from Schisandra rubriflora
Authors: Li Liang , Ren Hai‐Ying , Yang Xiao‐Dong , Zhao Jing‐Feng , Li Gan‐Peng , Zhang Hong‐Bin
Published: November 2004

From the stems of Schisandra rubriflora, two novel partially saturated dibenzocyclooctene lignans, named rubriflorin A (1) and B (6), as well as the seven known partially saturated dibenzocyclooctene lignans kadsumarin A (2), kadsurin (3), heteroclitin B (4), heteroclitin C (5), heteroclitin D (7), interiorin (8), and interiorin B (9) were isolated. The structures of the new compounds 1 and 6 were established on the basis of spectral analysis as (5R,6S,7R,8R,13aS)‐8‐(acetyloxy)‐5,6,7,8‐tetrahydro‐1,2,3,13‐tetramethoxy‐6,7‐dimethylbenz([3,4]cycloocta[1,2‐f][1,3]benzodioxol‐5‐yl (2Z)‐2‐methylbut‐2‐enoate and (6R,7R,12aS)‐7,8‐dihydro‐12‐hydroxy‐1,2,3,10,11‐pentamethoxy‐6,7‐dimethyl‐6H‐dibenzo[a,c]cycloocten‐5‐one, respectively.
Medical errors: The perspective of the insurer
Authors: James Thomas
Published: November 2004

Errors in medicine have a significant impact upon the cost of health insurance in the United States. These errors may reflect a range of errors ranging from ineffective or futile care to inappropriate medical judgments to coding errors. These may be unintentional, but underlying all of these error‐types is a failure of process stemming back to physician training. The commercial industries that pay for health insurance may be demanding a process approach and accountability structures in return for continued funding of health care services. J. Surg. Oncol. 2004;88:195–199. © 2004 Wiley‐Liss, Inc.
Is the chronologic age a contra‐indication for surgical palliation of unresectable periampullary neoplasms?
Authors: Nuzzo G. , Clemente G. , Greco F. , Ionta R. , Cadeddu F.
Published: November 2004

Methods

Early and late results of surgical palliation for unresectable periampullary neoplasms were evaluated in 24 patients older than 70 years and compared with the same results obtained from 33 younger patients. The two groups of patients were comparable, except for age. Biliary bypass associated to gastric bypass was the most common performed procedure.

Results

No significant differences in the results (morbidity, mortality, and outcome) were found in the two groups of patients. In addition, the results of palliative surgery in the elderly were compared with those obtained from a comparable group of 35 patients palliated with endoscopic stent insertion: surgical palliation resulted in better long‐term results.

Conclusions

This study provides evidence that the chronologic age is not a contra‐indication for surgical palliation of periampullary neoplasms and that surgery provides a better quality of residual life. J. Surg. Oncol. 2004;88:206–209. © 2004 Wiley‐Liss, Inc.
Neuropeptide Y alters stress‐induced changes in trace element concentrations of brain in chronically immobilized rats
Authors: Karakoc Yunus , Turhan Sibel , Yildirim Ejder Akgun , Mengi Murat , Yurdakos Ertan , Barutcu U. Bora
Published: November 2004

Central administration of neuropeptide Y (NPY) produces anxiolytic‐like behavioral responses in the conflict test, elevated plus maze, fear‐potentiated startle paradigm, and in the chronic immobilization stress. Exogenously administrated NPY also protects against the anxiogenic effects of corticotropin‐releasing factor. In the present study, we aimed to determine the effects of centrally administered NPY on the trace element disturbances in brain tissues (frontal and temporal lobes and brain stem) and the other major organs including liver, spleen (zinc [Zn]‐, copper [Cu]‐, and iron‐rich tissues), kidney, and stomach in chronically immobilized rats. The immobilization stress was performed in special cages in which the animals were not able to move. The rats in chronic stress and chronic stress + NPY groups were kept in the cages daily for 7 min for 15 consecutive days. Intracerebroventricular (ICV) cannulas were placed to the right lateral ventricles of the rats by using stereotaxic method. In the control and chronic stress groups, 5 μL of saline (NaCl 0.9%), and in the chronic stress + NPY group, 8 μg NPY/5 μL saline solutions, were administered into the brain via ICV cannula, respectively. Controls and immobilized rats were decapitated 30 min after the injections were over and samples of tissue were taken. Zn, Cu, and iron levels of the frontal lobe, temporal lobe, brain stem, liver, spleen, kidney, and stomach were determined by flame atomic absorption spectrophotometer. Zn and Cu levels were significantly increased in the frontal lobe, temporal lobe, and brain stem in response to chronic immobilization stress daily for 7 min for 15 consecutive days. The administration of NPY inhibited the elevation of Zn in these three parts of brain but did not affect the elevation of Cu in the frontal lobe and brain stem. Increases in Zn and Cu levels of frontal, temporal lobes, and brain stem may be related to induction of MT‐I mRNA expression by chronic immobilization stress, and NPY may affect this induction of MT‐I, altering corticotropin‐releasing factor release in the stress conditions. J. Trace Elem. Exp. Med. 17:283–290, 2004. © 2004 Wiley‐Liss, Inc.
Parameter Estimation of the Disk in a Floating Caliper Disk Brake Model with respect to Squeal
Authors: Jearsiripongkul Thira , Hagedorn Peter
Published: November 2004

Noise from a vehicle is always a concern for any automotive industry looking for passenger comfort. This also holds for the different types of brake noise, in particular for squeal, which is a source of discomfort both to passengers and passers‐by. Intensive research on low frequency squeal (noise between 1‐5 kHz) has been carried out. A model of the floating caliper disk brake has been recently proposed by the authors with the aim to predict the onset of squeal. A flutter type instability resulting from nonconservative restoring forces is assumed to be the reason behind squeal in this model. The problem of validating the model against experimental observation lies in the fact that all the system parameters included in the model, especially the disk, are to be carefully chosen. In this work some parameters of the disk are estimated and a method is suggested to estimate these parameters in a systematic way. For that purpose, the values are to be accurately selected by experiments and modal updating technique. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Hysteretic Friction of a Sliding Rubber Element
Authors: Lindner Markus , Sextro Walter , Popp Karl
Published: November 2004

Friction, especially friction of elastomers, can cause acoustic problems like noise, squeal and comfort drawbacks like vibrations and wear. Therefore, rubber friction affects the function of many products in technical applications, e.g. seals, belts and tires. It can be classified according to different physical phenomena like adhesion, hysteresis, cohesion and viscous friction, see [3]. The topic of this paper is hysteresis friction of rubber that is caused by the energy dissipation due to internal material damping during the process of deformation. The deformation itself occurs during the sliding of a rubber element across the micro‐scaled asperities of a rough surface. In this paper, the sliding process of a rubber element over real surfaces is simulated in time domain and compared to experiments. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Nichtlineare Schwingungs‐ und Stabilitätsanalysen für Seile
Authors: Thalheim J.‐U. , Heinen A. H.
Published: November 2004

Zur wirklichkeitsnahen Erfassung räumlicher Seilschwingungen ist es häufig notwendig, numerische Analysen auf der Basis nichtlinearer Bewegungsgleichungen durchzuführen. Insbesondere ist diese Vorgehensweise notwendig zur richtigen Erfassung von Instabilitätserscheinungen bei Seilkonstruktionen. Solche Instabilitätsphänomene sind z.B. bei Schrägseilbrücken infolge von Bewegungen der Pylone und des Fahrbahnträgers beobachtet worden (vgl. [5]). Ziel dieser Abhandlung ist es, mit nichtlinearen Seil‐ und Stabilitätsgleichungen, die im Vergleich zu Formulierungen in der Literatur [3]eine einfachere Struktur aufweisen, Schwingungs‐ und Stabilitätsuntersuchungen durchzuführen und die Ergebnisse ‐ soweit möglich ‐ mit Versuchsergebnissen zu vergleichen. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Stoßsimulation mittels einseitiger Feder‐Dämpfer Kontakte
Authors: Waltersberger Bernd , Keppler Rainer , Wauer Jörg
Published: November 2004

Die Verwendung von Feder‐Dämpfer Kontaktmodellen bei der Stoßsimulation ist häufig kontinuumsmechanisch begründet oder beispielsweise motiviert durch die Verwendung von Penalty Verfahren zur rechentechnischen Behandlung der Kontaktnebenbedingung. In dieser Arbeit wird untersucht, wie sich die Wahl der Kontaktbedingung aus den Alternativen Orts‐ bzw. Kraftbedingung (d.h. Kontakt wird angenommen, solange Eindringen vorliegt bzw. die Kontaktkraft eine Druckkraft ist) auf das Haftverhalten des Kontaktes auswirkt. Die Problematik wird anhand eines geradlinigen Stoßes eines Massepunktes auf ein Feder‐Dämpfer System untersucht, nachdem einführend ein einfaches kontinuumsmechanisches Modell eines axialen Stoßes eines Massepunktes auf einen Stab behandelt wird. Bei beiden Untersuchungen wird eine den Massepunkt belastende, konstante Kraft berücksichtigt, die besonders bei kleinen Stoßgeschwindigkeiten nicht mehr vernachlässigt werden darf. Für das Feder‐Dämpfer Kontaktmodell können die maßgeblichen Parameter und mit diesen die Bereiche unterschiedlichen Haftverhaltens angegeben werden. Abschließend wird gezeigt, wie die Überlegung zum einfachen geradlinigen Stoßvorgang auf Einfachstöße in der Mehrkörperdynamik nutzbringend angewandt werden kann. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Oscillations of Carbon Brushes in Hand‐held Electrical Tools
Authors: Yan Shuiping , Eiber Albrecht , Schiehlen Werner
Published: November 2004

A series‐universal motor is usually used in hand‐held electrical tools, such as cutting or grinding machines. The corresponding two carbon brushes are preloaded by springs to maintain a proper contact necessary to reduce their wear and erosion.

The oscillations of carbon brushes are coupled with the rotor motion. A model including carbon brushes and the main parts of tool rotor is described. By using the method of multibody systems the equations of motion are derived. The one‐sided contact forces and the electrical forces between commutator and brushes are mainly responsible for the nonlinear oscillations of brushes. The contour of contact surface is one of the major parameters of contact force.

There exist periods where the brushes are separated from the commutator, i.e. a free flight motion of carbon brush occurs. The measured and simulated results show that a large spring preload and a small brush mass improve the contact and result in reduced free flight periods. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Motion planning for a circular elastic plate
Authors: Woittennek Frank , Rudolph Joachim
Published: November 2004

Motion planning for finite time rest‐to‐rest transitions of a symmetric boundary controlled elastic plate is shown to be possible using operational calculus and series expansions. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Macroscopic Modelling of Vibration and Stability Problems in Prestressed Microperiodic Elastic Solids
Authors: Woźniak Czeslaw , Woźniak Margaret
Published: November 2004

The aim of this contribution is to propose and apply a certain averaged (macroscopic) mathematical model for the analysis of vibration and stability problems of prestressed microperiodic elastic solids. In contrast to the known homogenized model [2], [3] the proposed model describes the effect of the period length on the macroscopic solid behaviour. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
FE Modelling of NiTi‐Composed Structures
Authors: Christ Daniel , Reese Stefanie
Published: November 2004

The present contribution focuses on the finite element modelling of NiTi‐based shape memory alloys. For this purpose, the concept of Helm [1] has been further developed and implemented into a finite element formulation. The model is able to describe the multiaxial behaviour of SMA and therefore useful for the simulation of complex problems. Additional emphasis is put on the modelling of the shape memory effect in composites where the interaction between the alloy and other materials like e.g. polymers plays an important role. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Berechnung von Kohlenstoffnanoröhren mit Finiten Elementen
Authors: Ernst Gerald , Nasdala Lutz , Rothert Heinrich
Published: November 2004

Kraftfeldansätze für die Berechnung atomarer Strukturen können in die Finite Elemente Methode eingebettet werden. Standard‐Elemente sind jedoch nicht in der Lage, die Atomphysik adäquat wiederzugeben. Anhand von Berechnungen von Kohlenstoffnanoröhren wird gezeigt, dass ein neues 4‐Knoten‐Element geeignet ist, atomare Strukturen zuverlässig zu berechnen. Auch Defekte in der Struktur der Kohlenstoffnanoröhren können damit berücksichtigt werden. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
An Approximation for Electrically Semipermeable Edge Cracks and its Application to Fracture Analysis of PZT
Authors: Kessler H. , Balke H. , Jelitto H. , Schneider G. A.
Published: November 2004

Approximate intensity factors are calculated in four point bending by combination of the nonlinear piezoelectric Griffith crack solution with linear finite element solutions for the impermeable and completely permeable edge crack problem. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Prenatal diagnosis of DMD in a female foetus affected by Turner syndrome
Authors: Satre V. , Monnier N. , Devillard F. , Amblard F. , Lunardi Pr J.
Published: November 2004

Objectives

We report on a prenatal diagnosis of DMD complicated by a 45,X karyotype that was revealed only in the chorionic villus long‐term culture.

Methods

Cytogenetic investigations were performed on both short‐term (STC) and long‐term cultures (LTC) of the chorionic villus sample. Familial segregation was performed using a panel of intragenic polymorphic markers, and multiplex PCR was used to characterize exonic deletion.

Results

Investigations performed for sex determination after STC of the chorionic villus sample showed a normal karyotype 46,XX, while the karyotype performed after LTC revealed a homogeneous monosomy X. Cytogenetic analysis performed on amniotic fluid cells showed 45,X/46,XX mosaicism. Familial segregation analysis for DMD showed loss of heterozygosity for the STR49 marker in the DNA of the proband, her mother and the foetus. Dystrophin gene analysis on the 45,X cells led to the identification of a deletion of exon 50.

Conclusions

The report described a rare situation of monosomy X associated with a DMD genotype. The data confirmed the DMD carrier status of the proband and her mother and indicated that the foetus had a high risk to combine a Turner phenotype and DMD. This study illustrated the potential risk of using short‐term culture of villi as the only source of biological material for prenatal diagnosis. Copyright © 2004 John Wiley & Sons, Ltd.
Ultrasound diagnosis of fetal anomalies: an analysis of perinatal management of 318 consecutive pregnancies in a multidisciplinary setting
Authors: Bijma Hilmar H. , Schoonderwaldt Ernst M. , van der Heide Agnes , Wildschut Hajo I. J. , van der Maas Paul J. , Wladimiroff Juriy W.
Published: November 2004

Objectives

The objectives of this study are to analyse the perinatal management decisions made in a multidisciplinary setting following the prenatal diagnosis of fetal anomalies and to evaluate to what extent, in clinical practice, decisions about obstetric management are attuned to those about neonatal management.

Methods

Data on perinatal management of 318 consecutive singleton pregnancies presented to a multidisciplinary perinatal team in a tertiary centre were collected retrospectively.

Results

The multidisciplinary perinatal team decided upon non‐aggressive obstetric management in 20% of the cases and consented to termination of pregnancy in 10% of the cases. The multidisciplinary perinatal team decided upon neonatal management in 112(36%) of all fetuses. In 100(89%) of these fetuses, standard neonatal management, and in 12(11%), no neonatal life‐sustaining treatment was decided upon. Implementation of the decisions of the multidisciplinary perinatal team on the various management modalities ranged from 88 to 100%.

Conclusion

The multidisciplinary perinatal team worked well in making decisions about obstetric management. In 30% of the cases, this concerned end‐of‐life decisions. However, for the majority of cases, the perinatal team did not plan neonatal management before birth and thereby did not attune obstetric and neonatal management to each other. This probably reflects the different attitudes towards end‐of‐life decisions between obstetricians and neonatologists. However, to ensure a consistent perinatal management, a multidisciplinary perinatal team has to make prenatal decisions about both obstetric and neonatal management. Copyright © 2004 John Wiley & Sons, Ltd.
Age‐standardisation when target setting and auditing performance of Down syndrome screening programmes
Authors: Cuckle Howard , Aitken David , Goodburn Sandra , Senior Brian , Spencer Kevin , Standing Sue ,   on behalf of the UK National Down's Syndrome Screening Programme, Laboratory Advisory Group
Published: November 2004

Objective

To describe and illustrate a method of setting Down syndrome screening targets and auditing performance that allows for differences in the maternal age distribution.

Methods

A reference population was determined from a Gaussian model of maternal age. Target detection and false‐positive rates were determined by standard statistical modelling techniques, except that the reference population rather than an observed population was used. Second‐trimester marker parameters were obtained for Down syndrome from a large meta‐analysis, and for unaffected pregnancies from the combined results of more than 600 000 screens in five centres. Audited detection and false‐positive rates were the weighted average of the rates in five broad age groups corrected for viability bias. Weights were based on the age distributions in the reference population.

Results

Maternal age was found to approximate reasonably well to a Gaussian distribution with mean 27 years and standard deviation 5.5 years. Depending on marker combination, the target detection rates were 59 to 64% and false‐positive rate 4.2 to 5.4% for a 1 in 250 term cut‐off; 65 to 68% and 6.1 to 7.3% for 1 in 270 at mid‐trimester. Among the five centres, the audited detection rate ranged from 7% below target to 10% above target, with audited false‐positive rates better than the target by 0.3 to 1.5%.

Conclusion

Age‐standardisation should help to improve screening quality by allowing for intrinsic differences between programmes, so that valid comparisons can be made. Copyright © 2004 John Wiley & Sons, Ltd.
Mathematical modeling and numerical simulation of cell growth in injection molding of microcellular plastics
Authors: Osorio Andres , Turng Lih‐Sheng
Published: November 2004

A mathematical formulation and numerical simulation for non‐isothermal cell growth during the post‐filling stage of microcellular injection molding have been developed. The numerical implementation solves the energy equation, the continuity equation, and a group of equations that describe the mass diffusion of dissolved gas and growth of micro‐cells in a microcellular injection molded part. The “unit‐cell” model employed in this study takes into account the effects of injection and packing pressures, melt and mold temperatures, and super‐critical fluid content on the material properties of the polymer‐gas solution and the cell growth. The material system studied is a microcellular injection molded polyamide 6 (PA‐6) resin. Two Arrhenius‐type equations are used to estimate the coefficients of mass diffusion and solubility for the polymer‐gas solution as functions of temperature. The dependence of the surface tension on the temperature is also included in this study. The numerical results in terms of cell size across the sprue diameter agree fairly well with the experimental observation. The predicted pressure profile at the sprue location has also been found to be in good agreement with the dynamics of the cell growth. Whereas for conventional injection molding the pressure of the system tends to decay monotonously, the pressure profile in microcellular injection molding exhibits an initial decay resulting from cooling and the absence of packing followed by an increase due to cell growth that expands the polymer‐gas solution and helps to pack out the mold uniformly. Polym. Eng. Sci. 44:2274–2287, 2004. © 2004 Society of Plastics Engineers.
Electron ionization mass spectrometric study of 1,4‐dihydro‐4‐substituted 2,6‐dimethyl‐3,5‐bis(alkoxycarbonyl)pyridines
Authors: Salehi Hojatollah , Li Qianrong , Yin Hao , Ding Yi , Guo Qingxiang
Published: November 2004

Using the accurate masses obtained from a time‐of‐flight instrument and the tandem mass spectrometric (MS/MS) data from an ion trap instrument, electron ionization mass spectra of a series of 1,4‐dihydro‐4‐substituted 2,6‐dimethyl‐3,5‐bis(alkoxycarbonyl)pyridines are reported and rationalized. Two sets of fragmentation pathways are proposed. One involves the formation of fragment ions containing the 1,4‐dihydropyridine structure, and the other of ions containing a pyridine ring. Copyright © 2004 John Wiley & Sons, Ltd.
Coupling of fully automated chip electrospray to Fourier transform ion cyclotron resonance mass spectrometry for high‐performance glycoscreening and sequencing
Authors: Froesch Martin , Bindila Laura M. , Baykut Gökhan , Allen Mark , Peter‐Katalinić Jasna , Zamfir Alina D.
Published: November 2004

The NanoMate robot has been coupled to a Fourier transform ion cyclotron resonance (FTICR) mass spectrometer at 9.4 T and implemented for the first time for complex carbohydrate analysis. It was optimized in the negative ion mode to achieve automated sample delivery on the chip along with increased sensitivity, ultra‐high resolution and accurate mass determination. A novel bracket has been designed to allow a reliable mounting of the NanoMate to the Apollo electrospray ionization (ESI) source of an APEX II instrument. The notably higher efficiency of ionization for compositional mapping of complex mixtures and feasibility for fragmentation analysis of components by sustained off‐resonance irradiation collision‐induced tandem mass spectrometry (SORI‐CID MS2) has been demonstrated on a glycoconjugate mixture containing O‐glycosylated sialylated peptides from urine of a patient suffering from a hereditary N‐acetylhexosaminidase deficiency (Schindler's disease), previously analyzed by capillary‐based nanoESI‐FTICRMS, and of a healthy control person. Due to its potential to generate highly charged ionic species, reduce the in‐source fragmentation, increase sensitivity, reproducibility and ionization efficiency, along with the ability to generate a sustained and constant electrospray, this method can be considered as a new platform for advanced glycomics. Copyright © 2004 John Wiley & Sons, Ltd.
Characterization of limonin glucoside metabolites from human prostate cell culture medium using high‐performance liquid chromatography/electrospray ionization mass spectrometry and tandem mass spectrometry
Authors: Tian Qingguo , Kent Kyle D. , Bomser Joshua A. , Schwartz Steven J.
Published: November 2004

The metabolism of limonin 17‐β‐D‐glucopyranoside (LG) by non‐cancerous (RWPE‐1) and cancerous (PC‐3) human prostate epithelial cells was investigated using high‐performance liquid chromatography/electrospray ionization mass spectrometry (LC/ESI‐MS) with in‐source fragmentation and tandem mass spectrometry (MS/MS). During positive ion LC/ESI‐MS, LG formed an abundant sodiated species ([M+Na]+) while the protonated molecule was barely observable. [M+Na]+ further fragmented into the less abundant [LARL+H]+ and a predominantly protonated aglycone molecule (limonin) due to in‐source fragmentation. The major metabolite, limonin A‐ring lactone (LARL), formed an abundant protonated molecule that was fragmented into a protonated molecule of limonin by loss of one molecule of water. In MS/MS by collisionally activated dissociation (CAD), LG produced the sodiated aglycone, [aglycone+Na]+, while LARL fragmented into [M+H]+ of limonin and fragment ions resulted by further loss of water, carbon monoxide and carbon dioxide, indicating the presence of oxygenated‐ring structures. The limits of detection of LG were 0.4 and 20 fmol in selected‐ion monitoring (SIM) and selected‐reaction monitoring (SRM) detection, respectively. Copyright © 2004 John Wiley & Sons, Ltd.
GUD1 (YDL238c) encodes Saccharomyces cerevisiae guanine deaminase, an enzyme expressed during post‐diauxic growth
Authors: Saint‐Marc Christelle , Daignan‐Fornier Bertrand
Published: November 2004

Purine salvage is a complex pathway allowing a correct balance between adenylic and guanylic derivatives. In this paper, we show that GUD1 (YDL238c) encodes guanine deaminase, a catabolic enzyme producing xanthine and ammonia from guanine. Importantly, Gud1p activity was higher during post‐diauxic growth, suggesting that a decrease of the guanylic nucleotide pool could be required when cells shift from proliferation to quiescence. Copyright © 2004 John Wiley & Sons, Ltd.
Health status and mortality in Holocaust survivors living in Jerusalem 40–50 years later
Authors: Collins Chen , Burazeri Genc , Gofin Jaime , Kark Jeremy D.
Published: November 2004

The long‐term health sequelae of the Holocaust were assessed 40–50 years later in the framework of a Jerusalem community health study. Holocaust survivors (N = 288, mean age = 67.6 years) and European‐born Jews, not exposed to the Holocaust (N = 486, mean age = 68.9 years), were studied in 1985–87. Our objective was to compare psychobehavioral factors, clinical variables, and mortality outcomes. The comparisons revealed higher emotional distress scores in female Holocaust survivors than in unexposed women and poorer self‐appraised health status in male Holocaust survivors than unexposed men. A 10‐year mortality follow‐up that terminated in April 1996 showed no significant association with Holocaust exposure. Long‐term Holocaust survivors may represent a selective resilient group.
Vocational function among persons with schizophrenia with and without history of childhood sexual trauma
Authors: Lysaker Paul H. , Nees Michael A. , Lancaster Rebecca S. , Davis Louanne W.
Published: November 2004

This study examined whether history of childhood sexual abuse in schizophrenia is linked with severity of vocational deficits. Work performance was measured using the Work Behavior Inventory and hours of work performed in a vocational rehabilitation program and then compared for 12 participants with schizophrenia or schizoaffective disorder reporting abuse and 18 with schizophrenia with no abuse history. ANOVAs indicated that the sexual abuse group worked fewer hours during the first 4 weeks of the program and demonstrated poorer work performance overall. An interaction was found suggesting that the sexually abused group's performance declined as the nonsexually abused group improved overtime. Childhood sexual abuse may be associated with greater vocational deficits in adults with schizophrenia.
Dust deposition pulses to the eastern subtropical North Atlantic gyre: Does ocean's biogeochemistry respond?
Authors: Neuer Susanne , Torres‐Padrón M. E. , Gelado‐Caballero M. D. , Rueda M. J. , Hernández‐Brito J. , Davenport Robert , Wefer Gerold
Published: November 2004

Enhancement of primary and export production following dust deposition pulses is well established for High Nutrient Low Chlorophyll regions, but the effect of atmospheric dust on the biogeochemistry of oligotrophic gyre regions remains unclear. Here we report atmospheric dust concentrations measured on Gran Canaria, Canary Islands, concomitantly with upper water biogeochemistry at the oligotrophic time series station ESTOC (European Station for Time series in the Ocean, Canary Islands) during a 2‐year period from winter 1997 to 1999. ESTOC is located in the eastern subtropical Atlantic gyre about 100 km north of Gran Canaria and 500 km west of the Sahara, and receives aeolian dust episodically mainly in winter and summer. We found a close correlation of the magnitude of atmospheric dust concentration in winter with the magnitude of downward particle flux at ESTOC, mainly due to a relative increase in lithogenic matter and carbonate sedimentation. Higher aerosol concentration was not accompanied by higher primary or export production, however, indicating that phytoplankton production remained unaffected by atmospheric nitrogen supply on a seasonal or yearly timescale. However, by estimating bioavailable iron input and the need of the phytoplankton population, we found that the highly episodic dust pulses might exert a feast and famine effect on the phytoplankton. Despite the high lithogenic matter input, carbonate, mainly stemming from coccolithophorids, exceeded in importance the role of lithogenic matter as ballasting agent of sinking organic matter.
Comparison of five soil organic matter decomposition models using data from a 14C and 15N labeling field experiment
Authors: Pansu Marc , Bottner Pierre , Sarmiento Lina , Metselaar Klaas
Published: November 2004

Five alternatives of the previously published MOMOS model (MOMOS‐2 to ‐6) are tested to predict the dynamics of carbon (C) and nitrogen (N) in soil during the decomposition of plant necromass. 14C and 15N labeled wheat straw was incubated over 2 years in fallow soils of the high Andean Paramo of Venezuela. The following data were collected: soil moisture, total 14C and 15N and microbial biomass (MB)‐14C and ‐15N, daily rainfall, air temperature and total radiation. Daily soil moisture was predicted using the SAHEL model. MOMOS‐2 to ‐4 (type 1 models) use kinetic constants and flow partitioning parameters. MOMOS‐2 can be simplified to MOMOS‐3 and further to MOMOS‐4, with no significant changes in the prediction accuracy and robustness for total‐14C and ‐15N as well as for MB‐14C and ‐15N. MOMOS‐5 (type 2 models) uses only kinetic constants: three MB‐inputs (from labile and stable plant material and from humified compounds) and two MB‐outputs (mortality and respiration constants). MOMOS‐5 did not significantly change the total‐14C and ‐15N predictions but markedly improved the predictive quality and robustness of MB‐14C and ‐15N predictions (with a dynamic different from the predictions by other models). Thus MOMOS‐5 is proposed as an accurate and ecologically consistent description of decomposition processes. MOMOS‐6 extends MOMOS‐5 by including a stable humus compartment for long‐term simulations of soil native C and N. The improvement of the predictions is not significant for this 2‐year experiment, but MOMOS‐6 enables prediction of a sequestration in the stable humus compartment of 2% of the initially added 14C and 5.4% of the added 15N.
Seasonal variation of CO2 saturation in the Gulf of Bothnia: Indications of marine net heterotrophy
Authors: Algesten Grete , Wikner Johan , Sobek Sebastian , Tranvik Lars J. , Jansson Mats
Published: November 2004

Seasonal variation of pCO2 and primary and bacterioplankton production were measured in the Gulf of Bothnia during an annual cycle. Surface water was supersaturated with CO2 on an annual basis, indicating net heterotrophy and a source of CO2 to the atmosphere. However, the Gulf of Bothnia oscillated between being a sink and a source of CO2 over the studied period, largely decided by temporal variation in bacterial respiration (BR) and primary production (PP) in the water column above the pycnocline. The calculated annual respiration‐production balance (BR‐PP) was very similar to the estimated CO2 emission from the Gulf of Bothnia, which indicates that these processes were major determinants of the exchange of CO2 between water and atmosphere. The southern basin (the Bothnian Sea) had a lower net release of CO2 to the atmosphere than the northern Bothnian Bay (7.1 and 9.7 mmol C m−2 d−1, respectively), due to higher primary production, which to a larger extent balanced respiration in this basin.
A nested grid formulation for chemical transport over Asia: Applications to CO
Authors: Wang Yuxuan X. , McElroy Michael B. , Jacob Daniel J. , Yantosca Robert M.
Published: November 2004

A global three‐dimensional chemical transport model (GEOS‐CHEM) was modified to permit treatment of a limited spatial regime with resolution higher than that adopted for the global background. Identified as a one‐way nested grid formulation, the model was applied to a simulation of CO over Asia during spring 2001. Differences between results obtained using the nested grid (resolution 1° × 1°), the coarse global model (resolution 4° × 5°), and the intermediate global model (resolution 2° × 2.5°) are discussed. The higher‐resolution model allows for more efficient, advection‐related, ventilation of the lower atmosphere, reflecting the significance of localized regions of intense upward motion not resolved in a coarser‐resolution simulation. Budget analysis suggests that upward transfer to higher altitudes through large‐scale advection provides the major sink for CO below 4 km. Horizontal advection, mainly through the north boundary, contributes a net source of CO to the window domain despite the polluted nature of the study region. The nested‐grid model is shown to provide good agreement with measurements made during the Transport and Chemical Evolution over the Pacific (TRACE‐P) campaign in spring 2001, notably better than the low‐resolution model in simulating frontal lifting process and differences across the boundary separating the regions of cyclonic and anticyclonic flow. The high‐resolution window approach also allows us to differentiate transport mechanisms for individual subregions of China on a much finer scale than was possible previously. Suggestions are made as to how to allow for subgrid vertical advective motions in the low‐resolution model through a carefully designed and broadly tested eddy diffusion treatment.
Support vectors–based groundwater head observation networks design
Authors: Asefa Tirusew , Kemblowski Mariush W. , Urroz Gilberto , McKee Mac , Khalil Abedalrazq
Published: November 2004

This study presents a methodology for designing long‐term groundwater head monitoring networks in order to reduce spatial redundancy. A spatially redundant well does not change the potentiometric surface estimation error appreciably, if not sampled. This methodology, based on Support Vector Machines, makes use of a uniquely solvable quadratic optimization problem that minimizes the bound on generalized risk, rather than just the mean square error of differences between measured and “predicted” groundwater head values. The nature of the optimization problem results in sparse approximation of the function defining the potentiometric surface that was utilized to select the number and locations of long‐term monitoring wells and guide future data collection efforts, which is a prerequisite in building and calibrating regional flow and transport models. The methodology is applied to the design of regional groundwater monitoring networks in the Water Resources Inventory Area (WRIA) 1, Whatcom County, northern Washington State, USA.
Integrin specificity of the cyclic Arg‐Gly‐Asp motif and its role in integrin‐targeted gene transfer
Authors: Wittekindt Carsten , Böttger Michael , Höltje Hans‐Dieter , Schäfer‐Korting Monika , Cartier Régis , Haberland Annekathrin
Published: November 2004

Targeted gene transfer, addressing the αvβ3 integrin by coupling the appropriate ligand, cRGD (S2‐bridged cyclic Arg‐Gly‐Asp containing peptide) motif, on to a DNA condensing sequence was described as early as 1995 by Hart, Harbottle, Cooper, Miller, Williamson and Coutelle [(1995) Gene Ther. 2, 552–554]. Their work was followed by a series of publications, introducing the cRGD motif in polycationic DNA carriers, such as peptides, proteins and liposomes. Polyethylenimine and even adenoviruses were additionally ligated using the cRGD motif. ‘Integrin specificity’ has been determined from the significantly improved transfection efficiency compared with the DNA carriers with control ligands, mainly the cRGE (S2‐bridged cyclic‐Arg‐Gly‐Glu‐containing peptide) motif. However, by observing the physicochemical appearance of the resulting complexes and their controls such as the poly(l‐lysine)–DNA complexes carrying the cRGD and the cRGE motifs, we doubted the integrin‐mediated specificity of the increased transfection efficiency. To clarify this contradiction, we investigated the suitability of the cRGD motif for targeted gene transfer. We proved the specificity of the RGD motif and its controls using computational docking procedures and molecular modelling methods. Since we were confident of the motifs used, we improved our transfection method. Since aggregation of the RGD‐ligated poly(l‐lysine)–DNA complexes under physiological conditions caused an enormous amount of unspecific cell uptake and transfection, a method had to be designed to exclude aggregation processes of the motif‐polycation–DNA complexes. Small complex sizes are necessary for receptor‐specific uptake. The complexes were therefore recharged using poly(vinyl sulphate). Inhibited aggregation of the targeted DNA carriers under physiological conditions is a necessary prerequisite for successful in vivo gene transfer.
Structural studies of duck δ2 crystallin mutants provide insight into the role of Thr161 and the 280s loop in catalysis
Authors: SAMPALEANU Liliana M. , CODDING Penelope W. , LOBSANOV Yuri D. , TSAI May , SMITH G. David , HORVATIN Cathy , HOWELL P. Lynne
Published: November 2004

δ Crystallin, a taxon-specific crystallin present in avian eye lenses, is homologous to the urea cycle enzyme ASL (argininosuccinate lyase). Although there are two δ crystallin isoforms in duck lenses, dδc1 (duck δ1 crystallin) and dδc2 (duck δ2 crystallin), only dδc2 is catalytically active. Previous structural studies have suggested that residues Ser283 and His162 in the multi-subunit active site of dδc2/ASL are the putative catalytic acid/base, while the highly conserved, positively charged Lys289 is thought to help stabilize the carbanion intermediate. The strict conservation of a small hydroxy-containing residue (Thr or Ser) at position 161 adjacent to the putative catalytic base, as well as its proximity to the substrate in the S283A dδc2 enzyme–substrate complex, prompted us to investigate further the role this residue. Structures of the active T161S and inactive T161D dδc2 mutants, as well as T161D complexed with argininosuccinate, have been determined to 2.0 Å resolution. The structures suggest that a hydroxy group is required at position 161 to help correctly position the side chain of Lys289 and the fumarate moiety of the substrate. Threonine is probably favoured over serine, because the interaction of its methyl group with Leu206 would restrict its conformational flexibility. Residues larger than Thr or Ser interfere with substrate binding, supporting previous suggestions that correct positioning of the substrate's fumarate moiety is essential for catalysis to occur. The presence of the 280s loop (i.e. a loop formed by residues 270–290) in the ‘open’ conformation suggests that loop closure, thought to be essential for sequestration of the substrate, may be triggered by the formation of the carbanion or aci-carboxylate intermediates, whose charge distribution more closely mimics that of the sulphate ion found in the active-site region of the inactive dδc1. The 280s loop in dδc1 is in the closed conformation.
NALP1 is a transcriptional target for cAMP-response-element-binding protein (CREB) in myeloid leukaemia cells
Authors: SANZ Cristina , CALASANZ Maria J. , ANDREU Enrique , RICHARD Carlos , PROSPER Felipe , FERNANDEZ-LUNA Jose L.
Published: November 2004

NALP1 (also called DEFCAP, NAC, CARD7) has been shown to play a central role in the activation of inflammatory caspases and processing of pro-IL1β (pro-interleukin-1β). Previous studies showed that NALP1 is highly expressed in peripheral blood mononuclear cells. In the present study, we report that expression of NALP1 is absent from CD34+ haematopoietic blast cells, and its levels are upregulated upon differentiation of CD34+ cells into granulocytes and to a lesser extent into monocytes. In peripheral blood cells, the highest levels of NALP1 were observed in CD3+ (T-lymphocytes), CD15+ (granulocytes) and CD14+ (monocytes) cell populations. Notably, the expression of NALP1 was significantly increased in the bone marrow blast cell population of some patients with acute leukaemia, but not among tissue samples from thyroid and renal cancer. A search for consensus sites within the NALP1 promoter revealed a sequence for CREB (cAMP-response-element-binding protein) that was required for transcriptional activity. Moreover, treatment of TF1 myeloid leukaemia cells with protein kinase C and protein kinase A activators induced CREB phosphorylation and upregulated the mRNA and protein levels of NALP1. Conversely, ectopic expression of a dominant negative form of CREB in TF1 cells blocked the transcriptional activity of the NALP1 promoter and significantly reduced the expression of NALP1. Thus NALP1 is transcriptionally regulated by CREB in myeloid cells, a mechanism that may contribute to modulate the response of these cells to pro-inflammatory stimuli.