bluuebunny/crossref_metadata_2025 huggingface dataset:
Selective Toxicity
Authors: Block John H.
Published: November 2003

Most drugs can be considered toxic in that they replace the natural ligand for a receptor. A goal in drug design is to develop a molecule that is selective for a particular receptor located on a specific target organ or tissue. The molecule also will show selectivity for the target organism whether it is a mammal, bacterium, fungus, virus, parasite, or insect. Therefore, an ideal biologically active molecule will produce a specific pharmacological response without causing adverse reactions. There are at least four ways to improve a drug's selectivity. These methodologies are based on the biochemistry of the disease or the biochemistry of the drug's receptor, unequal distribution of the drug, differences in the target cell's structure, and the drug's stereochemical properties. Pharmacological classes differs in their ability to show selectivity. Cancer chemotherapeutic agents generally show poor selectivity, whereas phosphodiesterase inhibitors can be selective for a specific enzyme isoform. Most bacterial antibiotics show excellent selective toxicity for bacteria with minimal serious adverse reactions experienced by the patient. In contrast, antiviral and antifungal drugs can produce untoward reactions in patients. To improve patient acceptance, an important goal is to design the drug such that it be transported to the desired receptor and “ignore” other sites. This chapter reviews methods used to improve drug selectivity.
Antiviral Agents, DNA
Authors: Middleton Tim , Rockway Todd
Published: November 2003

The seven families of DNA viruses that cause disease in humans show tremendous variety in the relationships that they have with their hosts. This variety is reflected both in the disease states that they cause and the approaches used to develop antiviral drugs to treat them. The most successful antiviral tools have been nucleoside analogs, particularly those targeting the polymerases of herpesviruses and hepatitis virus B. The list of nucleoside analog drugs continues to expand as compounds are developed with greater potency or range, better bioavailability, or improved side effect profiles. Other viral targets have started to receive more attention, including helicases, proteases, and enzymes required for virion assembly. These targets should gain in importance as resistance to currently available drugs becomes more prevalent. In addition, expanding the list of viable viral targets is particularly important with regard to members of the parvovirus, papillomavirus, and polyomavirus families, which do not encode a viral polymerase. Some effective antiviral treatments have not targeted the virus but rather the immune response to the viral infection. An optimal immune response is critical to elimination of some classes of viruses, and exploiting this aspect of the host‐virus interaction provides another approach to antiviral drug development.
Rationale of Design of Anti‐HIVDrugs
Authors: Mehanna Ahmed S.
Published: November 2003

The acquired immunodeficiency syndrome disease, abbreviated AIDS, is caused by the retrovirus, human immunodeficiency virus subtype1 (HIV‐1). Infection with the virus leads to severe suppression of the immune system and potential exposure to the so‐called opportunistic infections such as pneumonia, which could be fatal. Most of the currently available anti‐AIDS medications are inhibitors for the reverse transcriptase and protease enzymes. The growing resistance to the currently available drugs requires developing new agents that act by different mechanisms beyond transcriptase and protease inhibition. Treatment of AIDS and development of anti‐HIV agents to stop the virus replication requires acquaintance with various steps of the virus life cycle and the mechanism of how it reproduces itself. The present chapter describes the molecular aspects of the AIDS virus including its structure, molecular biology, and life cycle. Approaches to design anti‐HIV drugs are presented with update on the status of anti‐HIV therapeutic agents in the light of the continuous growing viral mutation.
Anthelmintics
Authors: Griffith Robert K.
Published: November 2003

This chapter discusses the agents currently available for the treatment of helmintic infections in humans. Current therapy for helmintic infections is dominated by praziquantel, benzimidazoles, and ivermectin. Praziquantel is the drug of choice for trematode infections including all types of schistosomiasis and various flukes. Ivermectin is the drug of choice for onchocerciasis and most other forms of filariasis, often used in combination with albendazole. Benzimidazoles are drugs of choice for most infections caused by nematodes. Unfortunately, no significant new classes of anthelmintic drugs have been introduced in nearly 20 years.
Adrenergics and Adrenergic‐Blocking Agents
Authors: Griffith Robert K.
Published: November 2003

This chapter reviews the drugs currently available in the United States that exert their therapeutic effects through actions on α‐ and β‐adrenoceptors and biosynthesis, release, and processing of the neurotransmitter norepinephrine. Included in the review are drugs acting as selective and nonselective agonists and antagonists at both α‐ and β‐adrenoceptors, as well as drugs that interfere with norepinephrine biosynthesis and release. Therapeutic categories include antihypertensives, bronchodilators, antiglaucoma agents, vasopressors, and nasal decongestants. Structure‐activity relationships are reviewed as are the structure and function of various adrenoceptors. Briefly covered is the metabolism of representative drugs in each structural class as well as recent developments in approaches to new drugs in the areas of selective α
1A
‐antagonists for treatment of prostatic hypertrophy and selective β
3
‐agonists for treatment of obesity and diabetes.
Cholinergics
Authors: Cannon Joseph G.
Published: November 2003

The transmission of impulses throughout the cholinergic nervous system is mediated by acetylcholine, and compounds that produce their pharmacologic effects by mimicking or substituting for acetylcholine are called cholinergics or parasympathomimetics. Compounds that inhibit or inactivate the body's normal hydrolysis of acetylcholine by acetylcholinesterase in nervous tissue and/or by butyrylcholinesterase (pseudocholinesterase, cholinesterase) in the plasma are called anticholinesterases. The gross observable pharmacological effects of both types of compounds are quite similar. More recently, compounds have been found that enhance the release of acetylcholine from cholinergic nerve terminals, thus (like the anticholinesterases) producing cholinergic effects by an indirect mechanism. These concepts are discussed in this chapter.
Narcotic Analgesics
Authors: Aldrich Jane V. , Vigil‐Cruz Sandra C.
Published: November 2003

Narcotic analgesics such as morphine have been the mainstay for the treatment of severe pain, although these drugs are associated with serious adverse effects, most notably addiction liability and respiratory depression. Therefore there has been an intensive effort to find new therapeutic agents that retain the effectiveness of morphine, but do not have its undesired side effects. Compounds have been identified from a wide variety of chemical classes, from the rigid morphinan alkaloids to the flexible phenylpiperidines and the opioid peptides, which have affinity for opioid receptors. In recent years considerable effort has focused on identifying ligands, both agonists and antagonists, with affinity for delta (δ) and kappa (κ) opioid receptors as pharmacological tools and as potential therapeutic agents that would not have the side‐effect profile of morphine and other agonists that interact with mu (μ) opioid receptors. After the identification of the closely related opioid receptor‐like (ORL1) receptor and its endogenous ligand orphanin FQ/nociceptin, there has been considerable effort directed toward identifying agonists and antagonists for this receptor as well. This review discusses the structure‐activity relationships for each of the major classes of compounds that interact with the opioid receptors, along with ligands for the ORL1 receptors.
Cognition Enhancers
Authors: Eid Clark N. , Wu Yong‐Jin , Kinney Gene G.
Published: November 2003

Very little can be done to abate or control the progression of dementia, a clinical syndrome most commonly encountered later in life and manifested by impairments in cognition, language, and memory. The percentage of the world's elderly population is increasing, and so too is the need for effective pharmaceutical interventions for dementias such as Alzheimer's disease (AD), age‐associated memory impairment (AAMI), multi‐infarct dementia (MID), vascular dementia, and Parkinsonian dementia. Advances have been made in understanding the etiology of these diseases, but much remains to be discovered. In this chapter we have focused on the development of several therapeutic approaches that have in common the ability to modulate gated ion channels, and as such, have the potential to affect multiple neurotransmitter systems. Specifically, we discuss the structure‐activity relationship (SAR) and behavioral outcome for ligands interacting with the (1) γ‐aminobutyric acid subtype A benzodiazepine receptor (GABAA/BzR); (2) nicotinic acetylcholine receptor (nAChR); (3) serotonin subtype 3 receptor (5‐HT3R); and (4) the potassium M‐channel.
Familial cryptic translocation (2;17) ascertained through recurrent spontaneous abortions
Authors: Bruyere Helene , Rajcan‐Separovic Evica , Doyle J. , Pantzar Tapio , Langlois Sylvie
Published: November 2003

We report a young woman who presented with a reproductive history of three recurrent spontaneous abortions (RSA) and two neonatal deaths. Comparative genomic hybridization (CGH) was used to determine the chromosomal composition of the patient's last miscarriage. It showed the presence of monosomy for the distal end of chromosome 2 long arm (segment 2q37.2 to qter) and trisomy for the distal end of chromosome 17 long arm (segment 17q25 to qter). The mother was found to be a carrier for a cryptic translocation between chromosomes 2 and 17 long arms by fluorescence in situ hybridization using a subtelomeric probe for 17q. Retrospective CGH analysis on one baby who died neonatally showed that he had inherited the maternal translocation in the same unbalanced state as the last pregnancy loss. His detailed postmortem examination is reported. © 2003 Wiley‐Liss, Inc.
Clinical and molecular delineation of the Greig cephalopolysyndactyly contiguous gene deletion syndrome and its distinction from acrocallosal syndrome
Authors: Johnston Jennifer J. , Olivos‐Glander Isabelle , Turner Joyce , Aleck Kyrieckos , Bird Lynne M. , Mehta Lakshmi , Schimke R. Neil , Heilstedt Heidi , Spence J. Edward , Blancato Jan , Biesecker Leslie G.
Published: November 2003

Greig cephalopolysyndactyly syndrome (GCPS) is caused by haploinsufficiency of GLI3 on 7p13. Features of GCPS include polydactyly, macrocephaly, and hypertelorism, and may be associated with cognitive deficits and abnormalities of the corpus callosum. GLI3 mutations in GCPS patients include point, frameshift, translocation, and gross deletion mutations. FISH and STRP analyses were applied to 34 patients with characteristics of GCPS. Deletions were identified in 11 patients and the extent of their deletion was determined. Nine patients with deletions had mental retardation (MR) or developmental delay (DD) and were classified as severe GCPS. These severe GCPS patients have manifestations that overlap with the acrocallosal syndrome (ACLS). The deletion breakpoints were analyzed in six patients whose deletions ranged in size from 151 kb to 10.6 Mb. Junction fragments were found to be distinct with no common sequences flanking the breakpoints. We conclude that patients with GCPS caused by large deletions that include GLI3 are likely to have cognitive deficits, and we hypothesize that this severe GCPS phenotype is caused by deletion of contiguous genes. © 2003 Wiley‐Liss, Inc.
Expression of class μ glutathione‐S‐transferase in human liver and its association with hepatopathies
Authors: Engracia V. , Leite M.M.B.S. , Pagotto R.C. , Zucoloto S. , Barbosa C.A.A. , Mestriner M.A.
Published: November 2003

We studied the distribution of GSTM1 phenotypes in 611 individuals from an ethnically mixed sample of the Brazilian population who died from various causes. No influence of age, gender, or ethnicity was detected on the phenotypic distribution. In a sub‐sample of 66 alcoholic individuals compared with 399 non‐alcoholics there was almost a doubling of the odds ratio for GSTM1(0) individuals in the alcoholic category. The incidence of hepatopathies was higher in this group as well, and we observed a significant association of the null phenotype with cirrhosis. An excess of null phenotypes (374/611) was observed, and the allelic distribution was: GSTM1*A = 0.168, *B = 0.089, and *0 (null) = 0.743. © 2003 Wiley‐Liss, Inc.
Neuroarchitecture of the color and polarization vision system of the Stomatopod haptosquilla
Authors: Kleinlogel Sonja , Marshall N. Justin , Horwood Julia M. , Land Mike F.
Published: November 2003

The apposition compound eyes of stomatopod crustaceans contain a morphologically distinct eye region specialized for color and polarization vision, called the mid‐band. In two stomatopod superfamilies, the mid‐band is constructed from six rows of enlarged ommatidia containing multiple photoreceptor classes for spectral and polarization vision. The aim of this study was to begin to analyze the underlying neuroarchitecture, the design of which might reveal clues how the visual system interprets and communicates to deeper levels of the brain the multiple channels of information supplied by the retina. Reduced silver methods were used to investigate the axon pathways from different retinal regions to the lamina ganglionaris and from there to the medulla externa, the medulla interna, and the medulla terminalis. A swollen band of neuropil—here termed the accessory lobe—projects across the equator of the lamina ganglionaris, the medulla externa, and the medulla interna and represents, structurally, the retina's mid‐band. Serial semithin and ultrathin resin sections were used to reconstruct the projection of photoreceptor axons from the retina to the lamina ganglionaris. The eight axons originating from one ommatidium project to the same lamina cartridge. Seven short visual fibers end at two distinct levels in each lamina cartridge, thus geometrically separating the two channels of polarization and spectral information. The eighth visual fiber runs axially through the cartridge and terminates in the medulla externa. We conclude that spatial, color, and polarization information is divided into three parallel data streams from the retina to the central nervous system. J. Comp. Neurol. 467:326–342, 2003. © 2003 Wiley‐Liss, Inc.
Distribution and colocalization of cholecystokinin with the prohormone convertase enzymes PC1, PC2, and PC5 in rat brain
Authors: Cain Brian M. , Connolly Kelly , Blum Alissa , Vishnuvardham Daesety , Marchand James E. , Beinfeld Margery C.
Published: November 2003

During posttranslational processing to generate CCK 8, pro‐cholecystokinin (CCK) undergoes endoproteolytic cleavage at three sites. Several studies using endocrine and neuronal tumor cells in culture and recombinant enzymes and synthetic substrates in vitro have pointed to the subtilisin/kexin‐like enzymes prohormone convertase (PC) 1, PC2, and PC5 as potential candidates for these endoproteolytic cleavages. In these experimental models, they all appear to be able to cleave pro‐CCK to make the correct products. One rodent model has provided information about the role of PC2. PC2 knockout mouse brains had less CCK 8 than wild‐type, although a substantial amount of CCK was still present. The degree to which CCK levels were reduced in these mice was regionally specific. These data indicated that PC2 is important for normal production of CCK but that it is not the only endoprotease that is involved in CCK processing. To evaluate whether PC1 and PC5 are possible candidates for the other enzymes involved in CCK processing, the distribution of PC1, PC2, and PC5 mRNA was studied in rat brain. Their colocalization with CCK mRNA was examined using double‐label in situ hybridization. PC2 was the most abundant of these enzymes in terms of the intensity and number of cells labeled. It was widely colocalized with CCK. PC1 and PC5 mRNA‐positive cells were less abundant, but they were also widely distributed and strongly colocalized with CCK in the cerebral cortex, hippocampus, amygdala, ventral tegmental area, and substantia nigra zona compacta. The degree of colocalization of the enzymes with CCK was regionally specific. It is clear that PC1 and PC5 are extensively colocalized with CCK and could be participating in CCK processing in the rat brain and may be able to substitute for PC2 in its absence. These three enzymes may represent a redundant system to ensure production of biologically active CCK. J. Comp. Neurol. 467:307–325, 2003. © 2003 Wiley‐Liss, Inc.
Expression of L1 decreases during postnatal development of rat spinal cord
Authors: Akopians Alin , Runyan Steve A. , Phelps Patricia E.
Published: November 2003

L1 is a cell adhesion molecule that is highly expressed on developing axons and is associated with neurite outgrowth, guidance, and fasciculation. In this study we systematically examined L1 expression at all spinal levels across eight postnatal ages to detect regional and developmental differences. We observed striking changes in the developmental pattern of L1 expression between birth (P0) and adult ages, with intense L1‐immunopositive axons prevalent throughout the funiculi at P0 compared with predominantly L1‐immunonegative funicular axons in adults. At all ages and spinal levels examined, some L1‐positive dorsal root afferents entered the spinal cord, coursed in Lissauer's tract, and projected into the superficial dorsal horn and the dorsal columns, as well as across the dorsal commissure. Additional L1‐positive axons were detected consistently around the perimeter of the spinal cord, in the dorsolateral funiculus, and adjacent to the central canal. While specific L1‐labeled axons were detected at all ages, a pattern of segmental variation was observed within animals, with the highest levels of L1 expression detected in lumbar and sacral segments and the lowest in cervical spinal cord. The pattern of L1 immunoreactivity was compared to that of the growth‐associated protein GAP‐43 and the results indicated colabeling of most axons. These observations demonstrate that L1 is expressed on immature axons well into postnatal development, possibly until they have completed their differentiation. Furthermore, the L1‐positive axons that continue to be detected in adults are likely to be either unmyelinated or sprouting axons. J. Comp. Neurol. 467:375–388, 2003. © 2003 Wiley‐Liss, Inc.
Cytotoxicity of normal and activated rat monocytes analyzed by flow cytometry
Authors: Stehling Oliver , Grau Veronika , Steiniger Birte
Published: November 2003

Background

The cytotoxic potential of activated monocytes might play an important role during severe systemic immune reactions and thus needs further elucidation. As established cytotoxicity tests are not suitable for this purpose, we developed a flow cytometry–based method.

Methods

During acute renal allograft rejection in the rat, monocytes were harvested by vascular perfusion and then purified by Percoll density gradient centrifugation and subsequent immunomagnetic negative selection. For comparison, natural killer (NK) cells were similarly isolated from spleen homogenates. Cytotoxicity was determined by flow cytometry using the fluorescein isothiocyanate–labeled NK‐sensitive lymphoma Yac‐1 as target. Necrotic cells were identified by propidium iodide, and apoptotic cells were identified by MC 540. Cytotoxicity was determined by the calculation of a cytotoxicity coefficient, ζ. The ζ coefficient describes the interrelation between the reciprocal proportion of target cells in a sample and the specific cytotoxicity, simultaneously allowing estimation of the contribution of contaminating NK cells.

Results

The method showed a substantial cytotoxicity of activated monocytes and indicated different or additional cytotoxic mechanisms compared with NK cells. Our assay permitted a detailed study of effector and target cells and took cytotoxicity of contaminating cells into account.

Conclusions

The method is nonradioactive, easy to perform, and thus helpful in investigating the role of monocytes in several diseases. Cytometry Part A 56A:81–88, 2003. © 2003 Wiley‐Liss, Inc.
Dithizone‐14C labelling and characterization
Authors: D'Urso Antonino , Filer Crist N. , Suryan Mahendra , Peng C. T.
Published: November 2003

[Thiocarbonyl‐14C] Dithizone was prepared and characterized spectroscopically. Copyright © 2003 John Wiley & Sons, Ltd.
Inclined load capacity of suction caissons
Authors: Aubeny C. P. , Han S. W. , Murff J. D.
Published: November 2003

A simplified method of analysis for estimating lateral load capacity of suction caisson anchors based on an upper bound plasticity formulation is presented. The simplification restricts the analysis to caissons in uniform and linearly varying undrained strength profiles; nevertheless, its computational efficiency permits quick evaluation of a number of parameters affecting load capacity. The validity and limitations of the simplified formulation are demonstrated through comparisons to more rigorous finite element solutions. A series of sensitivity studies demonstrate the effects of various soil conditions and loading parameters. Copyright © 2003 John Wiley & Sons, Ltd.
Two zebrafish mutants, ebony and ivory, uncover benefits of neighborhood on photoreceptor survival
Authors: Goldsmith Paul , Baier Herwig , Harris William A.
Published: November 2003

Zebrafish offer a tractable system for the study of retinal development and degeneration, to provide insights into human retinal degeneration. We have begun to dissect the question of neighborhood effects on photoreceptor differentiation and survival through the isolation and characterization of mutants with retinal degeneration. We describe two mutants, ebony and ivory, isolated through a behavioral screen for blind mutants induced by ethyl nitrosourea mutagenesis. Chimeric analysis was conducted to attempt to rescue the photoreceptor degeneration. In ebony, the photoreceptor cell death was both cell autonomous and nonautonomous in nature, whilst the photoreceptor cell death was strikingly nonautonomous in ivory. The rescue at a distance is in keeping with a putative diffusible survival factor. We propose a density‐dependent nonautonomous neighborhood effect to explain these findings. © 2003 Wiley Periodicals, Inc. J Neurobiol 57: 235–245, 2003
Finite element analysis and evaluation of design limits for structural materials in a cyclic state of creep
Authors: Boulbibane M. , Ponter A. R. S.
Published: November 2003

In this paper a direct non‐time stepping method derived from the minimum theorems given by the authors (European Journal of Mechanics – A/Solids 2002; 21:915–925) is outlined. This method can be used in the prediction of the deformation and life assessment of structures subjected to cyclic mechanical and thermal loadings. It produces accurate predictions of failure modes based on material behaviour incorporated into constitutive equations. It also can be used to define limit loads related to certain design criteria.

Generally, for complex geometries and load histories, the identification of load histories that correspond to predefined design conditions, in the form of time or number of cycles to failure, can only be achieved by extensive and repeated calculations. For the Linear Matching Method, however, the representation of materially non‐linear stress and strain fields by linear behaviour with spatially varying moduli, indicates the possibility that direct evaluation of loads and temperature ranges that correspond to a design restriction may be evaluated directly through the construction of the exact cyclic state and via sequence of approximations. The technique employs the finite element method combined with the cyclic state solution. The description of the material behaviour is given by a non‐linear viscous model (Norton's law). It can also apply to any class of material behaviour that includes internal state variables. This technique has been applied successfully to a set of characteristics problems (Bree problem and plate containing a circular hole and subjected to radial temperature gradient). Copyright © 2003 John Wiley & Sons, Ltd.
On the numerical implications of multiplicative inelasticity with an anisotropic elastic constitutive law
Authors: Sansour Carlo , Bocko Jozef
Published: November 2003

The statement that theories of inelasticity at finite strains have arrived at a high level of development is only true in conjunction with isotropic material behaviour. From both points of view (theoretical and computational), the extension to anisotropic material behaviour seems to be a complicated task. The statement is especially true when the multiplicative decomposition of the deformation gradient is considered a basis for the formulation. Of special interest are questions related to the mathematical form of the stored energy function or, equivalently, of the constitutive relation for the material stress tensor as the thermodynamical force. This paper deals with the above issues. The anisotropic formulation is accomplished using the notion of structural tensors. Here we suggest that the privileged directions of the material should be transformed in a specific way under the action of the inelastic part of the deformation gradient. The inelastic behaviour is assumed to be governed by evolution equations of the unified type.

Numerically, we deal with the full multiplicative structure of the theory. The numerical treatment is developed in full detail. Expressions concerning the local iteration as well as the tangent operator are derived. Various numerical examples with applications to shells are presented which demonstrate the influence of anisotropy and the applicability of the theory. Copyright © 2003 John Wiley & Sons, Ltd.
Extending the functionality of the general‐purpose finite element package SEPRAN by automatic differentiation
Authors: Bischof C. H. , Bücker H. M. , Lang B. , Rasch A. , Risch J. W.
Published: November 2003

From an abstract point of view, a numerical simulation implements a mathematical function that produces some output from some given input. Derivatives (or sensitivities) of the function's output with respect to its input can be obtained—free from truncation error—by using a technique called automatic differentiation. Given a computer code in a high‐level programming language like Fortran, C, or C++, automatic differentiation generates another code capable of computing not only the original function but also its derivatives. Thus, the application of automatic differentiation significantly extends the functionality of a simulation package. For instance, automatic differentiation enables, in a completely mechanical fashion, the usage of derivative‐based optimization algorithms where the evaluation of the objective function comprises some given large‐scale engineering simulation. In this paper, the automatic differentiation tool ADIFOR is used to transform the general‐purpose finite element package SEPRAN. In doing so, we automatically transform the given 400000 lines of Fortran 77 into a new program consisting of 600000 lines of Fortran 77. We compare our approach with a traditional approach based on numerical differentiation and quantify its advantages in terms of accuracy and computational efficiency for a standard fluid flow problem. Copyright © 2003 John Wiley & Sons, Ltd.
SIMS: from research to production control
Authors: Werner Helmut W.
Published: November 2003

In 1958, when I joined the Philips Research Laboratories, there were a number of technological problems related to the analysis of solids within Philips that needed analytical support. Because the available (bulk) techniques did not give sufficient results, a new technique, later called secondary ion mass spectrometry (SIMS), was launched that involved the bombardment of a solid target with (primary) energetic ions, followed by mass analysis and ion detection of the sputtered (secondary) target ions.

The restrictions of the available infrastructure for such an analytical technique were many: there was no PC for data handling, no internet or database for literature search, the photocopying machine was not yet invented, communication with other scientists had to be done by mail (there was no fax, no E‐mail, no mobile phones) and, what was worse, SIMS was not considered to be a useful analytical technique compared with established techniques!

In the years that followed there were many advances:

The SIMS instrumentation was improved by better ion optics, advanced electronic equipment and was extended from sector type to quadrupole and finally to time‐of‐flight (TOF) mass spectrometers.

The methodology of SIMS was developed step by step (parameters such as lateral and depth resolution, detection limit and quantitative analysis were all optimized in turn).

The SIMS technique then made its entrance to solve problems in technology development.

In the last two decades SIMS has become an indispensable, reliable, quantitative analytical technique for production control in integrated circuit technology and the after‐sales care of integrated circuits. The philosophy of the provision of an analytical service at the Philips Research Laboratory (hereinafter referred to as ‘our laboratory’) is discussed. After the initial period, where every method (SIMS, AES, ESCA, RBS, etc.) was claimed to be ‘the only one’ (the panacea), we learned how to organize analytical service cost efficiently and for the optimum benefit of the ‘customer’. The core analytical techniques were concentrated in one department and the customer would profit from synergy by using several appropriate analytical techniques for the same problem.

Today, the latest developments in SIMS instrumentation keep pace with the latest challenges of the ultra‐large‐scale integration (ULSI) roadmap for integrated circuits, which indicates the dimensions of the circuits that are predicted for the years to come. Copyright © 2003 John Wiley & Sons, Ltd.
Time‐of‐flight SIMS characterization of hydrolysed organofunctional and non‐organofunctional silanes deposited on Al, Zn and Al–43.4Zn–1.6Si alloy‐coated steel
Authors: Bexell Ulf , Olsson Mikael
Published: November 2003

In this paper Al, Zn and Al–43.4Zn–1.6Si (AlZn) alloy‐coated steel have been treated with the organofunctional silane γ‐mercaptopropyltrimethoxysilane (γ‐MPS) and the non‐organofunctional silane 1,2‐bis(triethoxysilyl)ethane (BTSE). Also, a two‐step treatment of metal substrates was performed: the metal substrates were treated with the BTSE silane followed by a γ‐MPS treatment. The influence of metal substrate and the pH value of the silane film properties were investigated using time‐of‐flight secondary ion mass spectrometry (ToF‐SIMS).

The results show that the BTSE silane is fully hydrolysed but the γ‐MPS silane is not. The presence of negative ions of the type HSixOy− indicates that both types of silane films are highly cross‐linked via Si–O–Si bonds. The two‐step treatment gave a γ‐MPS silane layer on top of the BTSE silane layer but the thickness of the total silane film become thinner than for a single BTSE film, indicating that some of the BTSE is dissolved during the γ‐MPS deposition step. Furthermore, the ToF‐SIMS results show that the thiol group of the γ‐MPS silane is oxidized. Finally, no major influence, either in the positive or the negative mass spectra, from the different metal substrates could be detected for the silane films investigated. Copyright © 2003 John Wiley & Sons, Ltd.
Quantification issues in ToF‐SSIMS and AFM co‐analysis in two‐phase systems, exampled by a polymer blend
Authors: Gilmore I. S. , Seah M. P. , Johnstone J. E.
Published: November 2003

This study concerns the measurement of the surface properties of sensitive materials, exampled by a polymer blend of polyvinyl chloride (PVC) and polycarbonate (PC), by static secondary ion mass spectrometry (SSIMS) and atomic force microscopy (AFM) operated in force modulation microscopy mode. It is shown that SSIMS, although damaging the surface little, causes significant subsurface damage. This changes the material behaviour in the irradiated region and leads to changes in the AFM measurements of both the topography and nanomechanical parameters such as the elastic moduli. Alternatively, if AFM is conducted first, contact with the tip may lead to modification of the surface. In order to minimize damage, soft cantilevers (spring constant ∼0.1 N m−1) are used. It is recommended that analyses be conducted on identifiably equivalent or partially overlapping regions, where any damage effects may be separated. Because, in SSIMS, a flood gun neutralizer must be used that irradiates the whole sample, it is recommended that AFM analysis is conducted prior to SSIMS even if different areas of the same sample are to be studied. The fractional areas identified by atomic species in SSIMS and separately by AFM are both the same and give the consistent ratio PVC/PC = 44 : 56. Both of these analyses are characteristic of the substrate below the top monolayer. The fractional areas determined using molecular species in SSIMS and by G‐SIMS both give PVC/PC = 20 : 80, which is interpreted to show that more than half of the PVC surface is covered by a monolayer of PC. Copyright © 2003 John Wiley & Sons, Ltd.
Physicochemical properties, surface morphology and particle size distribution of precipitated silicas
Authors: Żurawska Jolanta , Krysztafkiewicz Andrzej , Jesionowski Teofil
Published: November 2003

The results presented are from a study on the production of highly dispersed silicas by their precipitation from solutions of sodium metasilicate and ammonium salts. The applied ammonium salts were NH4HCO3 and (NH4)2CO3. The precipitation process was conducted in the absence or presence of 1 wt.% non‐ionic surfactant (Rokanol K‐7, Rokafenol N‐6 or Rokafenol N‐9).

The highly dispersed silicas obtained were subjected to a physicochemical analysis typical for fillers. The analysis included estimation of the bulk density and the capacities to absorb water, dibutyl phthalate and paraffin oil. Particle size and morphology were evaluated using scanning electron microscopy. In addition, particle size distribution for the precipitated silicas was examined by dynamic light scattering.

Silicas with the best physicochemical properties were obtained by precipitation using ammonium hydrogen carbonate. In particular, the silica precipitated in the presence of 1 wt.% Rokafenol N‐9 demonstrated a magnificent capacity to absorb paraffin oil. Copyright © 2003 John Wiley & Sons, Ltd.
Threshold Al KLL Auger spectra of oxidized aluminium foils
Authors: Buckley A. N. , Hartmann A. J. , Lamb R. N. , Stampfl A. P. J. , Freeland J. W. , Coulthard I.
Published: November 2003

Threshold Al KLL Auger electron spectroscopy and K‐edge x‐ray absorption fine structure spectroscopy have been used to examine technical purity (99.5%) aluminium foil before and after chemical treatment that altered the thickness and degree of hydroxylation of the oxidized layer. Comprehensive surface chemical characterization was effected by means of monochromatized Al Kα‐excited photoelectron spectroscopy. Threshold Al KL2, 3L2, 3 spectra were obtained for three of the foils investigated and these spectra were in broad agreement with those observed previously for pure Al foil. The relative intensities of the spectral components for two of the foils were clearly consistent with the previously proposed assignment of the resonantly enhanced Auger component, situated between those arising from the metal and Al(III) oxide, to a thin interfacial layer. The threshold Auger spectra from the aluminium foil bearing the thickest and most hydroxylated oxidized layer were not obviously consistent with the interfacial layer model but O K‐edge spectra revealed that this surface layer was fundamentally different from the others and could have had a greater interfacial surface area. Copyright © 2003 John Wiley & Sons, Ltd.
Changes in cyanoprokaryote populations, Microcystis morphology, and microcystin concentrations in Lake Elphinstone (Central Queensland, Australia)
Authors: White Susan H. , Fabbro Larelle D. , Duivenvoorden Leo J.
Published: November 2003

Lake Elphinstone is a tropical inland water body in the far north of the Fitzroy Catchment in Central Queensland, Australia, and has experienced recurrent toxic cyanoprokaryote blooms since 1997. This article reports on an examination of the environmental conditions of the lake and the concurrent cyanoprokaryote species together with their toxicity. The lake was sampled three times during periods of high cyanoprokaryote cell concentrations. Successive changes in the dominant Microcystis species were accompanied by variation in the concentration of the hepatotoxin microcystin. Environmental parameters recorded during dominance by both the highly toxic species Microcystis panniformis and the nontoxic M. botrys are provided. Nutrient status, temperature, and light conditions were associated with species change within the blooms. Variation of microcystin concentrations coincided with speciation change (i.e., morphological variation) within the blooms. Also discussed is the environmental impact of toxin production by M. panniformis with respect to influence on cell division, energy states, and toxin photodegradation. Lake Elphinstone is the first Australian location reported to have M. panniformis. © 2003 Wiley Periodicals, Inc. Environ Toxicol 18: 403–412, 2003.
Polarised secretion of cytokines in primary human microvascular endothelial cells is not dependent on N‐linked glycosylation
Authors: Jurczyluk Julie , Brown David , Stanley Keith K
Published: November 2003

Human microvascular endothelial cells (HMVEC) grow in monolayers on Transwell filters and restrict permeability between the apical and basolateral media. We show that these cell monolayers are capable of sorting labelled endogenous proteins, including chemokines, growth factors and cytokines, to either the apical or basolateral media. IL‐8 and GMCSF were secreted predominantly into the apical medium, whereas MIC‐1 was secreted into the basolateral medium. This polarity did not correlate with glycosylation, as IL‐8 and MIC‐1 are both N‐glycosylated, but were sorted to opposite sides of the cell. IL‐6 is not glycosylated and did not display significant polarity in secretion. Similarly, the polarity of secretion of endogenous glycoproteins was not related to their glycosylation.
Ernährungsverhalten aus handlungsorientierter Sicht
Authors: Lippke Sonia , Sniehotta Falko F.
Published: November 2003

Zusammenfassung. In diesem Beitrag wird das Multistadienmodell der Gesundheitsverhaltensänderung (MSM) vorgestellt und auf Ernährung angewandt. Das MSM beschreibt Änderungsprozesse von Gesundheitsverhalten als sequentiellen Ablauf über die Stadien Präkontemplation, Kontemplation, Disposition, Präaktion, Implementierung, Fluktuation und Habituation. Zur Erfassung dieser Stadien wird ein interaktiver diagnostischer Algorithmus vorgeschlagen. Um Grundannahmen des Modells zu testen, wird untersucht inwiefern verschiedene sozialkognitive und behaviorale Kontrollvariablen dazu beitragen, zwischen den Stadien des MSMs zu differenzieren. Anhand einer querschnittlichen Online-Studie (N = 812) werden Unterschiede zwischen den untersuchten Kontrollvariablen über die Stufen des MSMs unter Anwendung von Varianzanalysen mit einfachen und polynomialen Kontrasten auf diskontinuierliche Muster hin überprüft. Im Ergebnis zeigen sich diskontinuierliche Muster für die Mehrzahl der untersuchten Variablen. Anhand dieser Unterschiedsmuster lassen sich die im Modell vorgesehenen Stadien begründen. Vor allem die explizite Integration der Planungskognitionen im MSM bewährt sich dabei empirisch. Es zeigt sich, dass für die Bestimmung aktionaler Phasen zeitliche Kriterien nicht sinnvoll sind.
Modeling the evolution of a fresh sea surface anomaly produced by tropical rainfall
Authors: Wijesekera Hemantha W. , Paulson Clayton A. , Skyllingstad Eric D.
Published: November 2003

The evolution of a rain‐produced, fresh surface anomaly observed in the western equatorial Pacific warm pool was modeled by use of the Princeton Ocean Model with Mellor‐Yamada turbulent closure. The simulation was forced by a wind stress of 0.12 N m−2 and surface cooling of 225 W m−2. Following spin‐up, 34‐mm average rainfall was applied over a small portion of the domain. When rainfall ceased, momentum was trapped in a 1‐m, fresh surface layer, and turbulent mixing was inhibited below the layer. Seven hours later, the surface density anomaly was reduced by an order of magnitude, and the surface velocity anomaly in the direction of the wind was 0.15 m s−1. The simulations show upwelling at the upwind edge of the anomaly and downwelling at the downwind edge with maxima of 15 and 35 m d−1, respectively. The momentum balance for the velocity component in the direction of the wind indicated that local acceleration, horizontal advection, and vertical diffusion were in approximate balance except at the downwind edge of the anomaly, where pressure gradient terms were also important. The budget of turbulent kinetic energy showed that shear production plus buoyancy production (or destruction) was approximately balanced by dissipation in much of the anomaly; advection and vertical turbulent transport terms were significant at some depths at the edges. The strength of the surface density front at the downwind edge of the anomaly tended to increase with time relative to the front at the upwind edge.
Momentum and heat fluxes via the eddy correlation method on the R/V L'Atalante and an ASIS buoy
Authors: Pedreros R. , Dardier G. , Dupuis H. , Graber H. C. , Drennan W. M. , Weill A. , Guérin C. , Nacass P.
Published: November 2003

In this paper, we present the results obtained with the eddy correlation method applied to data acquired during the Flux, Etat de mer et Télédetection en Condition de Fetch variable experiment onboard the R/V L'Atalante. We discuss the corrections made to account for platform motion and for the effects of mean airflow distortion. The data are compared to those obtained from a moored Air‐Sea Interaction Spar (ASIS) buoy and from the L'Atalante using the inertial dissipation method (IDM). The main results from eddy correlation method on L'Atalante are that the momentum flux in‐line with the mean wind, −〈u′w′〉, is overestimated by 18%, likely due to turbulent flow distortion around the ship. In contrast, the results for heat flux do not appear to be contaminated by turbulent flow distortion. Indeed, heat fluxes obtained using the sonic temperature on the L'Atalante and the ASIS buoy are very similar. The eddy correlation latent heat fluxes obtained on the L'Atalante using a refractometer are significantly higher than those obtained from the same sensor using the IDM.
Modeling the residual circulation of a coastal embayment affected by wind‐driven upwelling: Circulation of the Ría de Vigo (NW Spain)
Authors: Souto C. , Gilcoto M. , Fariña‐Busto L. , Pérez Fiz. F.
Published: November 2003

The barotropic and baroclinic nontidal circulations of the Ría de Vigo (NW Spain) are studied using the three‐dimensional finite difference model HAMSOM (Hamburg Shelf Ocean Model). The external forcing acting on the system includes winds, freshwater inflow in the inner part of the ria and all over its surface, and heat exchange with the atmosphere. Modeled velocity is compared with data from an AANDERAA DCM12 acoustic Doppler current meter at one site of the ria, and predicted salinity and temperature fields contrasted with SEABIRD conductivity‐temperature‐depth data along the main channel of the ria. All predicted current, salinity, and temperature fields are in good agreement with experimental data. A new residual circulation pattern of the Ría de Vigo and its dependence on coastal winds is described. According to this pattern the typical estuarine two‐layer circulation overlays in the outer part of the ria with a lateral circulation, resulting in a three‐dimensional dynamics. The lateral circulation is induced by interaction between the southward (northward) alongshore coastal jet associated with upwelling (downwelling) winds and the topographic configuration of the ria.
Global monitoring of air pollution over land from the Earth Observing System‐Terra Moderate Resolution Imaging Spectroradiometer (MODIS)
Authors: Chu D. A. , Kaufman Y. J. , Zibordi G. , Chern J. D. , Mao Jietai , Li Chengcai , Holben B. N.
Published: November 2003

Moderate Resolution Imaging Spectroradiometer (MODIS) measurements (7 channels: 0.47–2.1 μm, 250–500 m resolutions) provide us with new insights into the characteristics of global aerosols. MODIS retrieves not only aerosol loading but also the fraction of fine mode particle. In this paper we demonstrate MODIS capability for use in monitoring global, regional, and local air pollution. Three case studies in northern Italy, Los Angeles, and Beijing showed the conclusive results of applying MODIS‐derived aerosol optical depths (τa) to regional and local air pollution in terms of accuracy (Δτa = ±0.05 ± 0.2τa) and spatial sensitivity of the retrievals. Under stagnant condition, accumulated aerosol abundance can reach τa > 1 (at 0.55 μm) before being removed by wind or precipitation. The correlation found between Aerosol Robotic Network (AERONET) daily averaged τa and 24‐hour PM10 (particulate matter with diameter <10 μm) concentration (μg/m3) in northern Italy is encouraging with correlation coefficient ∼0.82. The derivation of PM concentration from satellite measurements may be possible once we know the detailed aerosol vertical distribution. To compare aerosol loading in different regions of the globe, we choose the two most populated regions (eastern China and India) and the two most industrialized regions (the eastern United States/Canada and western Europe). The time series of MODIS monthly mean τa from July 2000 to May 2001 depicts a strong seasonal variation with maxima in the spring/summer and minima in the winter. The clear separation between (1) the eastern United States/Canada and western Europe and (2) eastern China and India shows that the τa values in (2) are 50% to 2–3 times higher compared to those in (1). The enhancements of aerosol loading were due to smoke as originated from Montana/Idaho forest fires transported to the eastern United States in late August 2000 and dust outbreaks from Taklimakan and Gobi Deserts to eastern China as well as smoke from Southeast Asia to southern China in February–April 2001.
Hydrothermal plumes trapped by thermal stratification
Authors: Colomer Jordi , Serra Teresa , Soler Marianna , Casamitjana Xavier
Published: November 2003

Hydrothermal plume penetration through density interfaces has been widely studied in laboratory experiments. It has been found that competition between plume buoyancy and background stratification (parameterised as the Richardson number) is crucial in determining whether or not the plume will penetrate through a density interface. In this paper, we present the analysis of field data concerning two hydrothermal sediment‐laden plumes in a stratified lake. Measurements of the particle concentration within these plumes have been used to determine their vertical, spatial and temporal development in the water column. The results show that neither of the plumes penetrate the lake thermoclines for large Richardson numbers, which is in accordance with the results found in laboratory experiments.