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Notes: Abstract A broad array of biological responses, including cell polarization, movement, immune and inflammatory responses, and prevention of HIV-1 infection, are triggered by the chemokines, a family of structurally related chemoattractant proteins that bind to specific seven-transmembrane receptors linked to G proteins. Here we discuss one of the early signaling pathways activated by chemokines, the JAK/STAT pathway. Through this pathway, and possibly in conjunction with other signaling pathways, the chemokines promote changes in cellular morphology, collectively known as polarization, required for chemotactic responses. The polarized cell expresses the chemokine receptors at the leading cell edge, to which they are conveyed by rafts, a cholesterol-enriched membrane fraction fundamental to the lateral organization of the plasma membrane. Finally, the mechanisms through which the chemokines promote their effect are discussed in the context of the prevention of HIV-1 infection.

Notes: Abstract The T cell compartment of adaptive immunity provides vertebrates with the potential to survey for and respond specifically to an incredible diversity of antigens. The T cell repertoire must be carefully regulated to prevent unwanted responses to self. In the periphery, one important level of regulation is the action of costimulatory signals in concert with T cell antigen-receptor (TCR) signals to promote full T cell activation. The past few years have revealed that costimulation is quite complex, involving an integration of activating signals and inhibitory signals from CD28 and CTLA-4 molecules, respectively, with TCR signals to determine the outcome of a T cell's encounter with antigen. Newly emerging data suggest that inhibitory signals mediated by CTLA-4 not only can determine whether T cells become activated, but also can play a role in regulating the clonal representation in a polyclonal response. This review primarily focuses on the cellular and molecular mechanisms of regulation by CTLA-4 and its manipulation as a strategy for tumor immunotherapy.

Notes: Abstract Interleukin-10 (IL-10), first recognized for its ability to inhibit activation and effector function of T cells, monocytes, and macrophages, is a multifunctional cytokine with diverse effects on most hemopoietic cell types. The principal routine function of IL-10 appears to be to limit and ultimately terminate inflammatory responses. In addition to these activities, IL-10 regulates growth and/or differentiation of B cells, NK cells, cytotoxic and helper T cells, mast cells, granulocytes, dendritic cells, keratinocytes, and endothelial cells. IL-10 plays a key role in differentiation and function of a newly appreciated type of T cell, the T regulatory cell, which may figure prominently in control of immune responses and tolerance in vivo. Uniquely among hemopoietic cytokines, IL-10 has closely related homologs in several virus genomes, which testify to its crucial role in regulating immune and inflammatory responses. This review highlights findings that have advanced our understanding of IL-10 and its receptor, as well as its in vivo function in health and disease.

Notes: Abstract This review describes the contribution of noncytolytic mechanisms to the control of viral infections with a particular emphasis on the role of cytokines in these processes. It has long been known that most cell types in the body respond to an incoming viral infection by rapidly secreting antiviral cytokines such as interferon alpha/beta (IFN-alpha/beta). After binding to specific receptors on the surface of infected cells, IFN-alpha/beta has the potential to trigger the activation of multiple noncytolytic intracellular antiviral pathways that can target many steps in the viral life cycle, thereby limiting the amplification and spread of the virus and attenuating the infection. Clearance of established viral infections, however, requires additional functions of the immune response. The accepted dogma is that complete clearance of intracellular viruses by the immune response depends on the destruction of infected cells by the effector cells of the innate and adaptive immune system [natural killer (NK) cells and cytotoxic T cells (CTLs)]. This notion, however, has been recently challenged by experimental evidence showing that much of the antiviral potential of these cells reflects their ability to produce antiviral cytokines such as IFN-gamma and tumor necrosis factor (TNF)-alpha at the site of the infection. Indeed, these cytokines can purge viruses from infected cells noncytopathically as long as the cell is able to activate antiviral mechanisms and the virus is sensitive to them. Importantly, the same cytokines also control viral infections indirectly, by modulating the induction, amplification, recruitment, and effector functions of the immune response and by upregulating antigen processing and display of viral epitopes at the surface of infected cells. In keeping with these concepts, it is not surprising that a number of viruses encode proteins that have the potential to inhibit the antiviral activity of cytokines.

Notes: Abstract Recent advances in the understanding of T cell activation have led to new therapeutic approaches in the treatment of immunological disorders. One attractive target of intervention has been the blockade of T cell costimulatory pathways, which result in more selective effects on only those T cells that have encountered specific antigen. In fact, in some instances, costimulatory pathway antagonists can induce antigen-specific tolerance that prevents the progression of autoimmune diseases and organ graft rejection. In this review, we summarize the current understanding of these complex costimulatory pathways including the individual roles of the CD28, CTLA-4, B7-1 (CD80), and B7-2 (CD86) molecules. We present evidence that suggests that multiple mechanisms contribute to CD28/B7-mediated T cell costimulation in disease settings that include expansion of activated pathogenic T cells, differentiation of Th1/Th2 cells, and the migration of T cells into target tissues. Additionally, the negative regulatory role of CTLA-4 in autoimmune diseases and graft rejection supports a dynamic but complex process of immune regulation that is prominent in the control of self-reactivity. This is most apparent in regulation of the CD4+CD25+CTLA-4+ immunoregulatory T cells that control multiple autoimmune diseases. The implications of these complexities and the potential for use of these therapies in clinical immune intervention are discussed.

Notes: Abstract The bare lymphocyte syndrome (BLS) is a hereditary immunodeficiency resulting from the absence of major istocompatibility complex class II (MHCII) expression. Considering the central role of MHCII molecules in the development and activation of CD4+ T cells, it is not surprising that the immune system of the patients is severely impaired. BLS is the prototype of a "disease of gene regulation." The affected genes encode RFXANK, RFX5, RFXAP, and CIITA, four regulatory factors that are highly specific and essential for MHCII genes. The first three are subunits of RFX, a trimeric complex that binds to all MHCII promoters. CIITA is a non-DNA-binding coactivator that functions as the master control factor for MHCII expression. The study of RFX and CIITA has made major contributions to our comprehension of the molecular mechanisms controlling MHCII genes and has made this system into a textbook model for the regulation of gene expression.

Notes: Abstract The human T cell leukemia virus-1 (HTLV-1) is a retrovirus that causes adult T cell leukemia (ATL) and neurological disorder, the tropical spastic paraparesis (HAM/TSP). The pathogenesis apparently results from the pleiotropic function of Tax protein, which is a key regulator of viral replication. Tax exerts (a) trans-activation and -repression of transcription of different sets of cellular genes through binding to groups of transcription factors and coactivators, (b) dysregulation of cell cycle through binding to inhibitors of CDK4/6, and (c) inhibition of some tumor suppressor proteins. These effects on a wide variety of cellular targets seem to cooperate in promoting cell proliferation. This is an effective viral strategy to amplify its proviral genome through replication of infected cells; ultimately it results in cell transformation and leukemogenesis.

Notes: Abstract Helicobacter pylori is a gram negative, spiral, microaerophylic bacterium that infects the stomach of more than 50% of the human population worldwide. It is mostly acquired during childhood and, if not treated, persists chronically, causing chronic gastritis, peptic ulcer disease, and in some individuals, gastric adenocarcinoma and gastric B cell lymphoma. The current therapy, based on the use of a proton-pump inhibitor and antibiotics, is efficacious but faces problems such as patient compliance, antibiotic resistance, and possible recurrence of infection. The development of an efficacious vaccine against H. pylori would thus offer several advantages. Various approaches have been followed in the development of vaccines against H. pylori, most of which have been based on the use of selected antigens known to be involved in the pathogenesis of the infection, such as urease, the vacuolating cytotoxin (VacA), the cytotoxin-associated antigen (CagA), the neutrophil-activating protein (NAP), and others, and intended to confer protection prophylactically and/or therapeutically in animal models of infection. However, very little is known of the natural history of H. pylori infection and of the kinetics of the induced immune responses. Several lines of evidence suggest that H. pylori infection is accompanied by a pronounced Th1-type CD4+ T cell response. It appears, however, that after immunization, the antigen-specific response is predominantly polarized toward a Th2-type response, with production of cytokines that can inhibit the activation of Th1 cells and of macrophages, and the production of proinflammatory cytokines. The exact effector mechanisms of protection induced after immunization are still poorly understood. The next couple of years will be crucial for the development of vaccines against H. pylori. Several trials are foreseen in humans, and expectations are that most of the questions being asked now on the host-microbe interactions will be answered.

Notes: Abstract Our understanding of the X-linked lymphoproliferative syndrome (XLP) has advanced significantly in the last two years. The gene that is altered in the condition (SAP/SH2D1A) has been cloned and its protein crystal structure solved. At least two sets of target molecules for this small SH2 domain-containing protein have been identified: A family of hematopoietic cell surface receptors, i.e. the SLAM family, and a second molecule, which is a phosphorylated adapter. A SAP-like protein, EAT-2, has also been found to interact with this family of surface receptors. Several lines of evidence, including structural studies and analyses of missense mutations in XLP patients, support the notion that SAP/SH2D1A is a natural inhibitor of SH2-domain-dependent interactions with members of the SLAM family. However, details of its role in signaling mechanisms are yet to be unravelled. Further analyses of the SAP/SH2D1A gene in XLP patients have made it clear that the development of dys-gammaglobulinemia and B cell lymphoma can occur without evidence of prior EBV infection. Moreover, preliminary results of virus infections of a mouse in which the SAP/SH2D1A gene has been disrupted suggest that EBV infection is not per se critical for the development of XLP phenotypes. It appears therefore that the SAP/SH2D1A gene controls signaling via the SLAM family of surface receptors and thus may play a fundamental role in T cell and APC interactions during viral infections.

Notes: Abstract There is great heterogeneity in the way humans respond to medications, often requiring empirical strategies to find the appropriate drug therapy for each patient (the "art" of medicine). Over the past 50 years, there has been great progress in understanding the molecular basis of drug action and in elucidating genetic determinants of disease pathogenesis and drug response. Pharmacogenomics is the burgeoning field of investigation that aims to further elucidate the inherited nature of interindividual differences in drug disposition and effects, with the ultimate goal of providing a stronger scientific basis for selecting the optimal drug therapy and dosages for each patient. These genetic insights should also lead to mechanism-based approaches to the discovery and development of new medications. This review highlights the current status of work in this field and addresses strategies that hold promise for future advances in pharmacogenomics.

Notes: Abstract Phenobarbital (PB) response elements are composed of various nuclear receptor (NR)-binding sites. A 51-bp distal element PB-responsive enhancer module (PBREM) conserved in the PB-inducible CYP2B genes contains two NR-binding direct repeat (DR)-4 motifs. Responding to PB exposure in liver, the NR constitutive active receptor (CAR) translocates to the nucleus, forms a dimer with the retinoid X receptor (RXR), and activates PBREM via binding to DR-4 motifs. For CYP3A genes, a common NR site [DR-3 or everted repeat (ER)-6] is present in proximal promoter regions. In addition, the distal element called the xenobiotic responsive module (XREM) is found in human CYP3A4 genes, which contain both DR-3 and ER-6 motifs. Pregnane X receptor (PXR) could bind to all of these sites and, upon PB induction, a PXR:RXR heterodimer could transactivate XREM. These response elements and NRs are functionally versatile, and capable of responding to distinct but overlapping groups of xenochemicals.

Notes: Abstract Nitric oxide (NO), a simple free radical gas, elicits a surprisingly wide range of physiological and pathophysiological effects. NO interacts with soluble guanylate cyclase to evoke many of these effects. However, NO can also interact with molecular oxygen and superoxide radicals to produce reactive nitrogen species that can modify a number of macromolecules including proteins, lipids, and nucleic acids. NO can also interact directly with transition metals. Here, we have reviewed the non-3',5'-cyclic-guanosine-monophosphate-mediated effects of NO including modifications of proteins, lipids, and nucleic acids.

Notes: Abstract L-Arginine (2-amino-5-guanidinovaleric acid) is the precursor of nitric oxide, an endogenous messenger molecule involved in a variety of endothelium-mediated physiological effects in the vascular system. Acute and chronic administration of L-arginine has been shown to improve endothelial function in animal models of hypercholesterolemia and atherosclerosis. L-Arginine also improves endothelium-dependent vasodilation in humans with hypercholesterolemia and atherosclerosis. The responsiveness to L-arginine depends on the specific cardiovascular disease studied, the vessel segment, and morphology of the artery. The pharmacokinetics of L-arginine have recently been investigated. Side effects are rare and mostly mild and dose dependent. The mechanism of action of L-arginine may involve nitric oxide synthase substrate provision, especially in patients with elevated levels of the endogenous NO synthase inhibitor asymmetric dimethylarginine. Endocrine effects and unspecific reactions may contribute to L-arginine-induced vasodilation after higher doses. Several long-term studies have been performed that show that chronic oral administration of L-arginine or intermittent infusion therapy with L-arginine can improve clinical symptoms of cardiovascular disease in man.

Notes: Abstract Cells are constantly under threat from the cytotoxic and mutagenic effects of DNA damaging agents. These agents can either be exogenous or formed within cells. Environmental DNA-damaging agents include UV light and ionizing radiation, as well as a variety of chemicals encountered in foodstuffs, or as air- and water-borne agents. Endogenous damaging agents include methylating species and the reactive oxygen species that arise during respiration. Although diverse responses are elicited in cells following DNA damage, this review focuses on three aspects: DNA repair mechanisms, cell cycle checkpoints, and apoptosis. Because the areas of nucleotide excision repair and mismatch repair have been covered extensively in recent reviews (1, 2, 3, 4, 5, 6), we restrict our coverage of the DNA repair field to base excision repair and DNA double-strand break repair.

Notes: Abstract Cytochrome P450 CYP1B1 is a relatively recently identified member of the CYP1 gene family. The purpose of this commentary is to review the regulatory mechanisms, metabolic specificity, and tissue-specific expression of this cytochrome P450 and to highlight its unique properties. The regulation of CYP1B1 involves a variety of both transcriptional and post-transcriptional mechanisms. CYP1B1 can metabolize a range of toxic and carcinogenic chemicals in vitro but in some cases with a unique stereoselectivity. Estradiol 4-hydroxylation appears to be a characteristic reaction catalyzed by human CYP1B1. However, there are considerable species differences regarding the regulation, metabolic specificity, and tissue-specific expression of this P450. In humans CYP1B1 is overexpressed in tumor cells, and this has important implications for tumor development and progression and the development of anticancer drugs specifically activated by CYP1B1.

Notes: Abstract This article reviews current knowledge of the metabolism of drugs that contain fluorine. The strategic value of fluorine substitution in drug design is discussed in terms of chemical structure and basic concepts in drug metabolism and drug toxicity.

Notes: Abstract Substantial epidemiologic data support a role for vitamin D in cancer prevention. However, dose-limiting hypercalcemic effects have proved a major obstacle to the development of natural vitamin D as a cancer chemopreventive. Structure-activity studies have sought to disassociate the toxicities and chemopreventive activities of vitamin D, and a number of synthetic deltanoids (vitamin D analogs) have shown considerable promise in this regard. Several such compounds have chemopreventive efficacy in preclinical studies, as does natural vitamin D. Data supporting further development of agents of this class include in vitro and in vivo evidence of antiproliferative, proapoptotic, prodifferentiating and antiangiogenic activities. Ongoing studies are aimed at further defining the molecular mechanisms through which vitamin D and synthetic deltanoids affect gene expression and cellular fate. Additional efforts are focused on establishing the chemopreventive index (efficacy vs toxicity) of each synthetic deltanoid.

Notes: Abstract Calmodulin (CaM) is an essential protein that serves as a ubiquitous intracellular receptor for Ca2+. The Ca2+/CaM complex initiates a plethora of signaling cascades that culminate in alteration of cellular functions. Among the many Ca2+/CaM-binding proteins to be discovered, the multifunctional protein kinases CaMKI, II, and IV play pivotal roles. Our review focuses on this class of CaM kinases to illustrate the structural and biochemical basis for Ca2+/CaM interaction with and regulation of its target enzymes. Gene transcription has been chosen as the functional endpoint to illustrate the recent advances in Ca2+/CaM-mediated signal transduction mechanisms.

Notes: Abstract Originally known for its regulation of reproductive functions, estradiol, a lipophilic hormone that can easily cross plasma membranes as well as the blood-brain barrier, maintains brain systems subserving arousal, attention, mood, and cognition. In addition, both synthetic and natural estrogens exert neurotrophic and neuroprotective effects. There is increasing evidence that estrogen actions are mediated by nongenomic as well as direct and indirect genomic pathways. Although in vitro models have provided the most extensive evidence for neurotrophic and neuroprotective actions to date, there are also in vivo studies that support these actions.

Notes: Abstract Drug interactions have always been a major concern in medicine for clinicians and patients. Inhibition and induction of cytochrome P450 (CYP) enzymes are probably the most common causes for documented drug interactions. Today, many pharmaceutical companies are predicting potential interactions of new drug candidates. Can in vivo drug interactions be predicted accurately from in vitro metabolic studies? Should the prediction be qualitative or quantitative? Although some scientists believe that quantitative prediction of drug interactions is possible, others are less optimistic and believe that quantitative prediction would be very difficult. There are many factors that contribute to our inability to quantitatively predict drug interactions. One of the major complicating factors is the large interindividual variability in response to enzyme inhibition and induction. This review examines the sources that are responsible for the interindividual variability in inhibition and induction of cytochrome P450 enzymes.

Notes: Abstract G protein-coupled receptors (GPCRs) represent a major class of proteins in the genome of many species, including humans. In addition to the mapping of a number of human disorders to regions of the genome containing GPCRs, a growing body of literature has documented frequently occurring variations (i.e. polymorphisms) in GPCR loci. In this article, we use a domain-based approach to systematically examine examples of genetic variation in the coding and noncoding regions of GPCR loci. Data to date indicate that residues in GPCRs are involved in ligand binding and coupling to G proteins and that regulation can be altered by polymorphisms. Studies of GPCR polymorphisms have also uncovered the functional importance of residues not previously implicated from other approaches that are involved in the function of GPCRs. We predict that studies of GPCR polymorphisms will have a significant impact on medicine and pharmacology, in particular, by providing new means to subclassify patients in terms of both diagnosis and treatment.

Notes: Abstract The resurgence of tuberculosis worldwide has intensified research efforts directed at examining the host defense and pathogenic mechanisms operative in Mycobacterium tuberculosis infection. This review summarizes our current understanding of the host immune response, with emphasis on the roles of macrophages, T cells, and the cytokine/chemokine network in engendering protective immunity. Specifically, we summarize studies addressing the ability of the organism to survive within macrophages by controlling phagolysosome fusion. The recent studies on Toll-like receptors and the impact on the innate response to M. tuberculosis are discussed. We also focus on the induction, specificity, and effector functions of CD4+ and CD8+ T cells, and the roles of cytokines and chemokines in the induction and effector functions of the immune response. Presentation of mycobacterial antigens by MHC class I, class II, and CD1 as well as the implications of these molecules sampling various compartments of the cell for presentation to T cells are discussed. Increased attention to this disease and the integration of animal models and human studies have afforded us a greater understanding of tuberculosis and the steps necessary to combat this infection. The pace of this research must be maintained if we are to realize an effective vaccine in the next decades.

Notes: Abstract Although interleukin-18 is structurally homologous to IL-1 and its receptor belongs to the IL-1R/Toll-like receptor (TLR) superfamily, its function is quite different from that of IL-1. IL-18 is produced not only by types of immune cells but also by non-immune cells. In collaboration with IL-12, IL-18 stimulates Th1-mediated immune responses, which play a critical role in the host defense against infection with intracellular microbes through the induction of IFN-gamma. However, the overproduction of IL-12 and IL-18 induces severe inflammatory disorders, suggesting that IL-18 is a potent proinflammatory cytokine that has pathophysiological roles in several inflammatory conditions. IL-18 mRNA is expressed in a wide range of cells including Kupffer cells, macrophages, T cells, B cells, dendritic cells, osteoblasts, keratinocytes, astrocytes, and microglias. Thus, the pathophysiological role of IL-18 has been extensively tested in the organs that contain these cells. Somewhat surprisingly, IL-18 alone can stimulate Th2 cytokine production as well as allergic inflammation. Therefore, the functions of IL-18 in vivo are very heterogeneous and complicated. In principle, IL-18 enhances the IL-12-driven Th1 immune responses, but it can also stimulate Th2 immune responses in the absence of IL-12.

Notes: Abstract Interferon regulatory factors (IRFs) constitute a family of transcription factors that commonly possess a novel helix-turn-helix DNA-binding motif. Following the initial identification of two structurally related members, IRF-1 and IRF-2, seven additional members have now been reported. In addition, virally encoded IRFs, which may interfere with cellular IRFs, have also been identified. Thus far, intensive functional analyses have been done on IRF-1, revealing a remarkable functional diversity of this transcription factor in the regulation of cellular response in host defense. Indeed, IRF-1 selectively modulates different sets of genes, depending on the cell type and/or the nature of cellular stimuli, in order to evoke appropriate responses in each. More recently, much attention has also been focused on other IRF family members. Their functional roles, through interactions with their own or other members of the family of transcription factors, are becoming clearer in the regulation of host defense, such as innate and adaptive immune responses and oncogenesis.

Notes: Abstract At least nine closely related isoforms of adenylyl cyclases (ACs), the enzymes responsible for the synthesis of cyclic AMP (cAMP) from ATP, have been cloned and characterized in mammals. Depending on the properties and the relative levels of the isoforms expressed in a tissue or a cell type at a specific time, extracellular signals received through the G-protein-coupled receptors can be differentially integrated. The present review deals with various aspects of such regulations, emphasizing the role of calcium/calmodulin in activating AC1 and AC8 in the central nervous system, the potential inhibitory effect of calcium on AC5 and AC6, and the changes in the expression pattern of the isoforms during development. A particular emphasis is given to the role of cAMP during drug and ethanol dependency and to some experimental limitations (pitfalls in the interpretation of cellular transfection, scarcity of the invalidation models, existence of complex macromolecular structures, etc).

Notes: Abstract The neurohypophysial hormone arginine vasopressin (AVP) is a cyclic nonpeptide whose actions are mediated by the stimulation of specific G protein-coupled membrane receptors pharmacologically classified into V1-vascular (V1R), V2-renal (V2R) and V3-pituitary (V3R) AVP receptor subtypes. The random screening of chemical compounds and optimization of lead compounds recently resulted in the development of orally active nonpeptide AVP receptor antagonists. Potential therapeutic uses of AVP receptor antagonists include (a) the blockade of V1-vascular AVP receptors in arterial hypertension, congestive heart failure, and peripheral vascular disease; (b) the blockade of V2-renal AVP receptors in the syndrome of inappropriate vasopressin secretion, congestive heart failure, liver cirrhosis, nephrotic syndrome and any state of excessive retention of free water and subsequent dilutional hyponatremia; (c) the blockade of V3-pituitary AVP receptors in adrenocorticotropin-secreting tumors. The pharmacological and clinical profile of orally active nonpeptide vasopressin receptor antagonists is reviewed here.

Notes: Abstract In spite of its proven heuristic value, the dopamine hypothesis of schizophrenia is now yielding to a multifactorial view, in which the other monoamines as well as glutamate and GABA are included, with a focus on neurotransmitter interactions in complex neurocircuits. The primary lesion(s) in schizophrenia does not necessarily involve any of these neurotransmitters directly but could deal with a more general defect, such as a faulty connectivity of developmental origin. Nevertheless, a precise identification of neurotransmitter aberrations in schizophrenia will probably provide clues for a better understanding of the disease and for the development of new treatment and prevention strategies.

Notes: Abstract The mammalian thioredoxins are a family of small (approximately 12 kDa) redox proteins that undergo NADPH-dependent reduction by thioredoxin reductase and in turn reduce oxidized cysteine groups on proteins. The two main thioredoxins are thioredoxin-1, a cytosolic and nuclear form, and thioredoxin-2, a mitochondrial form. Thioredoxin-1 has been studied more. It performs many biological actions including the supply of reducing equivalents to thioredoxin peroxidases and ribonucleotide reductase, the regulation of transcription factor activity, and the regulation of enzyme activity by heterodimer formation. Thioredoxin-1 stimulates cell growth and is an inhibitor of apoptosis. Thioredoxins may play a role in a variety of human diseases including cancer. An increased level of thioredoxin-1 is found in many human tumors, where it is associated with aggressive tumor growth. Drugs are being developed that inhibit thioredoxin and that have antitumor activity.

Notes: Abstract Cyclic ADP-ribose (cADPR) and nicotinic acid adenine dinucleotide phosphate (NAADP) are two Ca2+ messengers derived from NAD and NADP, respectively. Although NAADP is a linear molecule, structurally distinct from the cyclic cADPR, it is synthesized by similar enzymes, ADP-ribosyl cyclase and its homolog, CD38. The crystal structure of the cyclase has been solved and its active site identified. These two novel nucleotides have now been shown to be involved in a wide range of cellular functions including: cell cycle regulation in Euglena, a protist; gene expression in plants; and in animal systems, from fertilization to neurotransmitter release and long-term depression in brain. A battery of pharmacological reagents have been developed, providing valuable tools for elucidating the physiological functions of these two novel Ca2+ messengers. This article reviews these recent results and explores the implications of the existence of multiple Ca2+ messengers and Ca2+ stores in cells.

Notes: Abstract Antisense oligonucleotides have been used for more than a decade to downregulate gene expression. Phosphodiester oligonucleotides are nuclease sensitive, and the more nuclease-resistant phosphorothioate oligonucleotides are now in common use in the laboratory and have entered clinical trials. However, these molecules are highly bioactive and may inhibit gene expression by more than one mechanism. Although some dramatic successes have been demonstrated, it can still be difficult to properly interpret experimental data derived from the use of this class of oligonucleotide. This review discusses some of these issues with particular reference to a major area of current interest-inhibition of bcl-2 expression in tumor cells.

Notes: Abstract Natural killer cells express inhibitory receptors specific for MHC class I proteins and stimulatory receptors with diverse specificities. The MHC-specific receptors discriminate among different MHC class I alleles and are expressed in a variegated, overlapping fashion, such that each NK cell expresses several inhibitory and stimulatory receptors. Evidence suggests that individual developing NK cells initiate expression of inhibitory receptor genes in a sequential, cumulative, and stochastic fashion. Superimposed on the receptor acquisition process are multiple education mechanisms, which act to coordinate the stimulatory and inhibitory specificities of developing NK cells. One process influences the complement of receptors expressed by individual NK cells. Other mechanisms may prevent NK cell autoaggression even when the developing NK cell fails to express self-MHC-specific inhibitory receptors. Together, these mechanisms ensure a self-tolerant and maximally discriminating NK cell population. Like NK cells, a fraction of memory phenotype CD8+ T cells, as well as other T cell subsets, express inhibitory class I-specific receptors in a variegated, overlapping fashion. The characteristics of these cells suggest that inhibitory receptor expression may be a response to prior antigenic stimulation as well as to poorly defined additional signals. A unifying hypothesis is that both NK cells and certain T cell subsets initiate expression of inhibitory receptors in response to stimulation.

Notes: Abstract This paper contains recollections of some of the people and events that influenced the development of toxicology as an academic discipline. It also describes my experiences in pharmacology at the University of Chicago and the University of Kansas Medical Center and concludes with speculation concerning the future of toxicology. Moderation in all things/Ne quid nimis. -Terence in Andria

Notes: Abstract The mechanisms of general anesthesia in the central nervous system are finally yielding to molecular examination. As a result of research during the past several decades, a group of ligand-gated ion channels have emerged as plausible targets for general anesthetics. Molecular biology techniques have greatly accelerated attempts to classify ligand-gated ion channel sensitivity to general anesthetics, and have identified the sites of receptor subunits critical for anesthetic modulation using chimeric and mutated receptors. The experimental data have facilitated the construction of tenable molecular models for anesthetic binding sites, which in turn allows structural predictions to be tested. In vivo significance of a putative anesthetic target can now be examined by targeted gene manipulations in mice. In this review, we summarize from a molecular perspective recent advances in our understanding of mechanisms of action of general anesthetics on ligand-gated ion channels.

Notes: Abstract DNA topoisomerases are double-edged swords. They are essential for many vital functions of DNA during normal cell growth. However, they are also highly vulnerable under various physiological and nonphysiological stresses because of their delicate act on breaking and rejoining DNA. These stresses (e.g. exposure to topoisomerase poisons, acidic pH, and oxidative stresses) can convert DNA topoisomerases into DNA-breaking nucleases, resulting in cell death and/or genomic instability. The importance of topoisomerase-mediated DNA cleavage in tumor cell death and carcinogenesis has been recognized. This review focuses on recent findings concerning the molecular mechanisms of the stress responses to topoisomerase-mediated DNA damage. The involvement of ubiquitin/26S proteasome and SUMO/UBC9 in these processes, as well as the role of topoisomerase cleavable complexes in apoptotic cell death are discussed.

Notes: Abstract In the future, biomarkers will play an increasingly important role in all phases of drug development, including regulatory review. However, only a few of these biomarkers will become established well enough to serve in regulatory decision making as surrogate endpoints, thereby substituting for traditional clinical endpoints. Even generally accepted surrogate endpoints are unlikely to capture all the therapeutic benefits and potential adverse effects a drug will have in a diverse patient population. Accordingly, combinations of biomarkers probably will be needed to provide a more complete characterization of the spectrum of pharmacologic response. In the future, pharmacogenomic approaches, including those based on differential expression of gene arrays, will provide panels of relevant biomarkers that can be expected to transform the drug development process.

Notes: Historical analysis of the topic of women and smoking has concentrated on the early part of the twentieth century and on the challenge which smoking by ‘new women’ or ‘flappers’ offered to dominant notions of womanly behaviour. This paper considers, rather, the dominant constructions of women and smoking in the UK offered through the prism of changing versions of public health in the last fifty years. The construction of women and smoking, it is argued, has been emblematic of those policy agendas within public health and has borne a reciprocal relationship to them. The traditional view of women as mothers has been renegotiated and redefined through the new scientific alliances of late twentieth-century public health. These constructions have helped to set the parameters of discussion within which policy has been made.

Notes: Books reviewed in this article:Karen Dubinsky, The Second Greatest Disappointment: Honeymooning and Tourism at Niagara FallsKathleen Anne McHugh, American Domesticity: From How-to Manual to Hollywood MelodramaLeila J. Rupp, A Desired Past: A Short History of Same-Sex Love in AmericaJohn C. Spurlock and Cynthia A. Magistro, New and Improved: The Transformation of American Women's Emotional CultureJessica Weiss, To Have and To Hold: Marriage, the Baby Boom and Social Change

Notes: Books reviewed in this article:Paul Goodman, Of One Blood: Abolitionism and the Origins of Racial EqualityLeslie A. Schwalm, A Hard Fight for We: Women's Transition from Slavery to Freedom in South CarolinaAmy Dru Stanley, From Bondage to Contract: Wage Labor, Marriage and the Market in the Age of Slave EmancipationMarli Weiner, Mistresses and Slaves: Plantation Women in South Carolina, 1830–1880

Notes: Books reviewed:Ulinka Rublack, The Crimes of Women in Early Modern GermanyMargaret L. Arnot and Cornelie Usborne (eds), Gender and Crime in Modern EuropeMichael B. Young, James VI and I and the History of HomosexualityDavid Cressy, Travesties and Transgressions in Tudor and Stuart England: Tales of Discord and DissensionIsobel Grundy, Lady Mary Wortley Montagu: Comet of the Enlightenment Mary Waldron, Jane Austen and the Fiction of her TimeRadhika Singha, A Despotism of Law: Crime & Justice in Early Colonial IndiaAfsaneh Najmabadi, The Story of the Daughters of Quchan: Gender and National Memory in Iranian History

Notes: This paper examines return migrants and new migrants to Montana: Who are they? Why do they move? Do return migrants move for different reasons than new migrants? Data from the 1994–1997 Montana Poll, a representative survey of Montana households, are used. A comparison of socio-economic differences of return and new migrants shows that the two migrant types are very similar in terms of education, income, and age. This stands in contrast to the findings of others who maintain that return migrants are negatively selected with respect to education. Logistic regressions were employed to identify the effect of age and place ties on reasons for moving. Return migrants and new migrants move to Montana for very similar reasons, with family being the most important primary reason for moving. Moving for lifestyle reasons, such as environmental quality and urban amenities, were found to systematically change with age. This could explain why people return to a place they left earlier in life. While other research on return migration compared return migrants and other migrants who left the same place of origin, this paper offers a comparison of return migrants and other migrants who seek out the same destination. Results from the Montana Poll suggest that the same destination attracts return migrants and new migrants with similar socio-economic characteristics who move there for very similar reasons.

Notes: This research explores the role of place in corporate location strategy by following the global footsteps of pharmaceutical giant Eli Lilly and Company. Examining a life science company model whose acquisitions strongly affected industry strategy provides examples of place characteristics modifying high tech corporate strategy in four very different metropolitan areas: Indianapolis, Research Triangle, San Diego and Shanghai. Targeted interviews explore institutional, human, and place features. This case study illustrates why choosing the best learning location—where both structured and informal information exchange networks can nurture companies—is key to achieving competitive advantage through site selection.

Notes: This paper departs from the existing growth literature in not assuming a priori a specific production technology and offering instead a theory of production technology that captures the effects of changes in the level, composition, and forces of accumulation of capital on the productivity of an economy. The theory of production technology shows that an affluent knowledge-rich economy violates the Inada second condition because of its high level of knowledge, human, and social capital. Substitution of knowledge capital for physical capital and the self-reinforcing nature of the process of accumulation of knowledge, human, and social capital are the engines of growth in such economies. Poor economies, on the other hand, may exhibit neoclassical production technology of diminishing returns to capital and get trapped into a low-level steady state owing to their ever-growing need for physical capital and also to unfavorable supply conditions for knowledge capital, lower levels of knowledge, human, and social capital in these economies being inadequate to trigger the self-reinforcing dynamics. The mechanics of endogenous growth are essentially different in rich and poor economies because the production possibility surface is non-convex in the former, and this difference explains the sustained divergence of their growth rates.

Notes: The aim of this paper is to challenge the characterization of paid informal work as a form of employment based on exploitative relations that should be eradicated. Using empirical evidence gathered through structured interviews with 511 households in deprived and affluent neighborhoods in British cities, this paper reveals that paid informal work in deprived areas is mostly conducted for kin, neighbors, and friends for co-operative reasons and is thus more like unpaid community exchange in the private sphere than exploitative employment. In consequence, the challenge for social and labor market policy is argued to be not to try to eradicate such work but to harness it in these deprived urban neighborhoods.

Notes: The effectiveness of intra-regional job search is influenced by how far people are willing to travel to new employment. While much has been written on the commuting patterns of those in work, relatively little research has been carried out on how far unemployed job seekers are prepared to commute. This paper presents and tests a model of factors influencing the maximum time unemployed job seekers would be willing to travel to a potential new job. Significant effects are found for a range of personal and demographic characteristics, including gender, years of education, type of job, and location. The evidence suggests support for the spatial mismatch hypothesis and shows differing accessibility to employment opportunities for certain types of unemployed people. The findings also suggest that models of the trade-off between leisure and work time should fully include travel-to-work time as part of this trade-off.

Notes: Recent studies have identified factors statistically related to differences in state economic growth. These findings relate to regional policy because they appear to identify political options that could then be justified as improving growth. This paper evaluates the reliability of these studies as policy guides. It finds that most statistical conclusions are fragile and are ttherefore risky policy guides Economic base theory performs well, and provides the most reliable state level policy options. These policies, however, have to be crafted carefully to avoid pitfalls associated with traditional (and perhaps unpopular) basic industries.

Notes: Books reviewed:Aura Reggiani, (ed.) Spatial Economic Science. New Frontiers in Theory And MethodologyFrans Boekema, Kevin Morgan, Silvia Bakers, and Roel Rutten, (eds.) Knowledge, Innovation and Economic Growth–The Theory and Practice of Learning RegionsGary E.Machlis and Donald R. Field, (eds.)National Parks and Rural Development: Practice And Policy in the United StatesJohn Kromer, Neighborhood Recovery: Reinvestment Policy for the New Hometown

Notes: One of the debates around new firm formation across sub-national territories focuses on whether regional differences in industrial structure are more important influences than regional differences in individual industry performance. The present research, using Value Added Tax (VAT) registration data, attempts to make a contribution to this debate in the United Kingdom (UK) context using a shift-share covariance model. Firm de-registrations and, as a consequence, net changes in firm stocks are also analyzed with similar questions in mind. The findings show that although the effects of industrial mix are significant across most regions, in several key regional contexts the industrial competitive effect dominates. The issue of the role of regional industrial concentration forms a second major theme of this paper. This basically involves a questioning as to whether concentration is a positive or negative force for new firm formation. The results of this research indicate that industrial concentration, measured through localization, is more important for firm deaths than for firm births (although significant for both), but not particularly relevant to the understanding of the net outcome of entry and exit processes. In the UK, regions with higher levels of industry concentration seem to be associated overall with relatively lower levels of both firm births and deaths.

Notes: Books reviewed: Hong Kong as a Global Metropolis, by David R. Meyer. Globalization and Networked Societies: Urban-Regional Change in Pacific Asia, by Yue-man Yeung. Regional Cohesion and Competition in the Age of Globalization, edited by Hirotada Kohno, Peter Nijkamp and Jacques Poot. Employee Benefits and Labor Markets in Canada and the United States, edited by William T. Alpert and Stephen A. Woodbury. The Atlanta Paradox, edited by David L. Sjoquist. The Economics of Sports, edited by William S. Kern. Environmentally Sustainable Economic Development, by Asayehgn Desta.

Notes: The effect of immigration on state and local budgets is a frequent topic of both political and academic conversations. A controversial issue among scholars is whether or not immigration induces outmigration of low income native born residents, a population movement which would potentially have implications for the jurisdictional distribution of immigration's fiscal impact. It is hypothesized here that if interstate poverty migration occurred, it should cause fiscal spillovers by distributing some of the public sector burden of immigration from immigrant “host” states to neighboring states. This paper uses cross-sectional state data from 1988–1995 to explore the relationship between immigration in neighbor states and state redistributive expenditures. The results suggest that there is a positive relationship between immigration to neighboring states and redistributive expenditures. While most discussion of the fiscal impact of immigration has focused on the effects on host states and localities, the implications of these findings are that there are fiscal spillovers to neighboring states, suggesting that fiscal impacts on host states have been over-estimated and effects on neighboring states have been underestimated. Additionally, the implications of recent welfare reform, which gives states the opportunity to use citizenship as a criterion for program eligibility, are discussed.

Notes: Measuring nonuse values is one of the most controversial topics facing environmental economists today. One important issue that has received little attention is determining who has economic standing with respect to nonuse losses from natural resource injuries. In this paper, a conceptual model for determining compensable nonuse losses is developed that is consistent with the Kaldor-Hicks principle of potential Pareto improvement, and then that model is applied to the results of a telephone survey on industrial water pollution in the lower Passaic River in northern New Jersey. One proposition from this model indicates that only people who have knowledge of the injured resource (i.e., 10 to 44 percent of respondents) can incur a compensable nonuse loss. A second proposition from the model indicates that demand for information about an injury to a familiar resource is a necessary condition for compensable nonuse losses. It was found that 81 percent of the respondents who were familiar with the lower Passaic River were likely to read, listen to, or watch a news story about the river. However, far fewer respondents familiar with the lower Passaic River were willing to engage in more active, and costly, information-acquisition activities (such as conducting research at the library and attending public meetings). Finally, the model suggests that geographic proximity to nondescript resources may affect nonuse values, information costs, or both, helping define the potentially affected population. The empirical results for the lower Passaic River support this third proposition. The overall conclusion is that only a small fraction of the population in New Jersey and New York might reasonably experience a nonuse loss as a result of industrial water pollution in the lower Passaic River.

Notes: Sustainable development has become the dominant concept in the study of interactions between the economy and the biophysical environment, as well as a generally accepted goal of environmental policy. So far, economists have predominantly applied standard or neo-classical theory to environmental economic problems. In this article it will be argued that to fully understand a transformation of the economic system towards sustainability, standard environmental economics needs to be complemented by an evolutionary approach, that focuses the attention on irreversible, path-dependent change and long-run mutual selection of environmental and economic processes and systems. The article provides an overview of the main existing evolutionary contributions to environmental economics. Furthermore, a number of research directions of an evolutionary approach in environmental economics are discussed. It is suggested that such an approach should go beyond evolutionary theories of technical change, which dominate evolutionary economics so far, by including co-evolution of economy and environment, sustainable consumption, endogenous preference change, and climate change modeling.

Notes: Nicholas Wolterstorff's Divine Discourse attempts to give philosophical warrant to the claim that ‘God speaks’. While Wolterstorff's argument depends largely on his appropriation of J.L. Austin's speech act theory, he also uses two narratives that for him demonstrate how ‘God speaks’. The first is the story of Augustine's conversion in the Confessions and the second is a story that Wolterstorff recounts about a certain ‘Virginia’. This study argues that what Wolterstorff claims to derive from Augustine's narrative for his view of divine discourse is not fully supported by the Confessions, and that Augustine's interpretation of the words ‘tolle lege, tolle lege’, can be construed as a useful interpretation of an ambiguous sign. This is consistent with Augustine's understanding of the interpretation of texts in both the De doctrina christiana and the Confessions. In short, Augustine is far more open to the ambiguity of signs than Wolterstorffs's account suggests.

Notes: ‘The Place of Geometry’ discusses the excursus on mathematics from Heidegger's 1924–25 lecture course on Platonic dialogues, which has been published as Volume 19 of the Gesamtausgabe as Plato's Sophist, as a starting point for an examination of geometry in Euclid, Aristotle and Descartes. One of the crucial points Heidegger makes is that in Aristotle there is a fundamental difference between arithmetic and geometry, because the mode of their connection is different. The units of geometry are positioned, the units of arithmetic unpositioned. Following Heidegger's claim that the Greeks had no word for space, and David Lachterman's assertion that there is no term corresponding to or translatable as ‘space’ in Euclid's Elements, I examine when the term ‘space’ was introduced into Western thought. Descartes is central to understanding this shift, because his understanding of extension based in terms of mathematical co-ordinates is a radical break with Greek thought. Not only does this introduce this word ‘space’ but, by conceiving of geometrical lines and shapes in terms of numerical co-ordinates, which can be divided, it turns something that is positioned into unpositioned. Geometric problems can be reduced to equations, the length (i.e, quantity) of lines: a problem of number. The continuum of geometry is transformed into a form of arithmetic. Geometry loses position just as the Greek notion of ‘place’ is transformed into the modern notion of space.

Notes: There is risk of intellectual dishonesty in the act of modernizing traditional doctrines. One reason theologians reform traditional doctrines is that the original formulations have become incredible to them. This is seldom honestly admitted. It is further dishonestly claimed that new formulations have a direct conceptual link to the old as if the new were the old retold. However, many times the connection between the new theology and the old is in name only, with radically new understanding for an old term. Can we honestly say so? Theology should resuscitate questions of intellectual honesty that were present at the Liberal theology's origins in the interest of maximizing honest theological inquiry. Can theology construct an ethics of belief for itself?

Notes: Books reviewed:Patrick H. Alexander, et al(ed), The SBL Handbook of Style for Ancient Near Eastern, Biblical and Early Christian StudiesC. E. B. Cranfield, On Romans and Other New Testament Essays The Christ and the Spirit: Collected Essays of James D. G. Dunn. Paul Heelas (ed), Religion, Modernity and PostmodernityJohn P. Newport, The New Age Movement and the Biblical Worldview: Conflict and DialogueJanet Hamilton and Bernard Hamilton, Christian Dualist Heresies in the Byzantine World, c. 650–1405: Selected SourcesLotte Kéry, Canonical Collections of the Early Middle Ages (c. 400–1140): A Bibliographical Guide to the Manuscripts and LiteratureGilbert Dahan, The Christian Polemic against the Jews in the Middle AgesGary Macy, Treasures from the Storeroom: Medieval Religion and the EucharistEric Cahm, The Dreyfus Affair in French Society and PoliticsAlistair Kee, Nietzsche Against the CrucifiedMary Jo Iozzio, Self-Determination and the Moral Act: A Study of the Contributions of Odon Lottin, O.S.B.Peter Glasner and Harry Rothman (eds), Genetic Imaginations: Ethical, Legal and Social Issues in Human Genome ResearchFrank J. Coppa (ed), Encyclopedia of the Vatican and Papacy

Notes: Data collected in seven separate samples in three countries (the USA, Canada and Israel) were used to examine the relationships between perceptions of one’s organization (climate, commitment), beliefs about appraisal systems (self-efficacy, uses of appraisal) and raters’ orientations to appraisal systems (confidence and comfort) and specific rating behaviors. We obtained good fits for structural models suggesting that attitudes and beliefs accounted for substantial variance in raters’ likelihood of giving high or low ratings, willingness to discriminate good from poor performers, and willingness to discriminate among various aspects of job performance when completing actual performance ratings. Proximal attitudes and beliefs (i.e., those directly related to the performance appraisal system) appear to have stronger links to rating behavior than do more distal attitudes (i.e., attitudes toward the organization in general).

Notes: In this article the relationship between higher level employees’ age and assessments of professional expertise is described. Hypotheses have been tested with original survey data from 417 higher level employees and 224 direct supervisors. Concerning the analyses of the effects of age, our hypotheses have for the greater part been confirmed. In our study, we have found that age-related stereotyping is an important phenomenon where assessments concerning professional expertise are made by supervisors. As regards the self-ratings, there is no relationship between age and professional expertise. Further research is needed to understand the pattern of differences between the two types of ratings. Some speculations concerning improvements of the measurements are discussed.

Notes: To demonstrate the multidimensionality of test fairness, we examined the reactions of 246 police applicants to two consecutive selection tests (written and video-based) in terms of eight dimensions of fairness. As hypothesized, each test was seen as more fair in terms of certain dimensions. Furthermore, test fairness measured immediately after each test predicted perceptions of overall selection system fairness measured after candidates received their test results and after controlling for applicants’ selection outcomes (i.e., whether they were eligible for further consideration in the selection process). Job-relatedness/content for the video-based test interacted with test score to affect test-taking self-efficacy. Our discussion focuses on the multidimensionality of test fairness, the contribution of these dimensions to overall selection system fairness, and the consideration of these dimensions in selection system design.

Notes: Books reviewed:Daniel R. Ilgen and Elaine D. Pulakos (eds) The Changing Nature of Performance: Implications for Staffing, Motivation, and DevelopmentD. Doverspike and R. Yuel The Difficult Hire: Seven Recruitment and Selection Principles for Hard to Fill Positions. Impact PublicationsFritz Drasgow and Julie B. Olson-Buchanan Innovations in Computerized Assessment

Notes: This article concerns leadership effectiveness studied from the reverse angle. We review the literature on managerial derailment and propose a taxonomy of derailment factors. We then describe an inventory designed to assess these factors, provide some evidence regarding the psychometric features of the inventory, and some evidence regarding its validity. We suggest that the base rate for managerial incompetence in any organization is quite high, and we propose our inventory is a useful device for management development – because it focuses on dysfunctional dispositions known to be associated with failure as a manager.

Notes: This article focuses on personality measures constructed for prediction of individual differences in particular work behaviors of interest (e.g., violence at work, employee theft, customer service). These scales can generically be referred to as criterion-focused occupational personality scales (COPS). Examples include integrity tests (which aim to predict dishonest behaviors at work), violence scales (which aim to predict violent behaviors at work), drug and alcohol avoidance scales (which aim to predict substance abuse at work), stress tolerance scales (which aim to predict handling work pressures well) and customer service scales (which aim to predict serving customers well). We first review the criterion-related validity, construct validity and incremental validity evidence for integrity tests, violence scales, stress tolerance scales, and customer service scales. Specifically, validities for counterproductive work behaviors and overall job performance are summarized as well as relations with the Big Five personality scales (conscientiousness, emotional stability, openness to experience, agreeableness and extraversion). Second, we compare the usefulness of COPS with traditional, general purpose, adult personality scales. We also highlight the theoretical and practical implications of these comparisons and suggest a research agenda in this area.

Notes: Books Reviewed:Peter Auer, Employment revival in Europe. Labour market success in Austria, Denmark, Ireland and the NetherlandsFranz Traxler, Sabine Blaschke and Bernhard Kittel, National Labour Relations in Internationalised Markets: A Comparative Study of Institutions, Change, and PerformanceRichard Whittington and Michael Mayer, The European Corporation: Strategy, Structure, and Social ScienceBernard Casey and Michael Gold, Social Partnership and Economic Performance: The Case of EuropeDüsseldorf: Hans-Böckler Foundation, The South East Europe Review for Labour and Social Affairs

Notes: This article considers the impact of European integration on industrial relations. An industrial relations regime can be understood as a tension between employment structured by market dynamics and broader social regulation, between the principles of contract and status. Economic Europeanisation threatens this relationship. Its survival may depend on new forms of supranational regulation, but not necessarily as the ‘social dimension’ of Europeanisation is customarily conceived.

Notes: The literature on Eastern Europe usually points to the desperate economic situation and hostile employers as explanations for post-communist union weakness. This paper examines an alternative explanation based on mobilisation theory. It argues that a major reason for labour quiescence is the incapability of unions to mobilise their membership which is partly hindered by unions' failure to modernise their communist role identity.

Notes: The article examines how non-union forms of employee representation impact on employee attitudes to unionisation. Through an analysis of union derecognition and the introduction of an employee council in an aerospace plant, it explores a number of factors that may be important in both sustaining and undermining support for trade unions.

Notes: Mean subgroup (gender, ethnic/cultural, and age) differences are summarized across studies for several predictor domains – cognitive ability, personality and physical ability – at both broadly and more narrowly defined construct levels, with some surprising results. Research clearly indicates that the setting, the sample, the construct and the level of construct specificity can all, either individually or in combination, moderate the magnitude of differences between groups. Employers using tests in employment settings need to assess accurately the requirements of work. When the exact nature of the work is specified, the appropriate predictors may or may not have adverse impact against some groups. The possible causes and remedies for adverse impact (measurement method, culture, test coaching, test-taker perceptions, stereotype threat and criterion conceptualization) are also summarized. Each of these factors can contribute to subgroup differences, and some appear to contribute significantly to subgroup differences on cognitive ability tests, where Black–White mean differences are most pronounced. Statistical methods for detecting differential prediction, test fairness and construct equivalence are described and evaluated, as are statistical/mathematical strategies for reducing adverse impact (test-score banding and predictor/criterion weighting strategies).

Notes: This article examines the evolution of Indian industrial relations in an historical and structural context. In India, the evolution of industrial relations has been ‘incremental’ and ‘adaptive’ and not ‘discontinuous’ and ‘revolutionary’. The relationship between changing industrialisation strategies and industrial relations institutions and practices in India is considerably more subtle than is often supposed in comparative industrial relations narratives, especially when detailed endogenous political economy considerations are taken into account.

Notes: Books reviewed: Social Change in Western Europe Colin Crouch Confronting Change: Auto Labor and Lean Production in North America Huberto Juárez Nuñez and Steve Babson (Editors)

Notes: The purpose of this paper is to provide a critical analysis of the impact of the privatisation of social security on Chile's economy and society. The paper also includes a brief discussion of Chile's current economic problems, and suggestions for integrating the social security system into the future development of the country. Its central argument is that social security should be able to provide adequate benefits not only to a privileged group of people, but to the entire society. In the case of Chile, the privatised system has created new sources of inequities, reduced the population coverage, and it has had a limited impact on economic development.

Notes: This article uses Sweden as an example to describe and analyse municipal variation in services and care for elderly people. Responsibility for these services lies with the municipalities. National statistical data on municipalities are analysed to map out the variations in old-age care; to study compensating factors in the care system; and to explore the connection with municipal structural and political conditions. The overall finding of the bivariate analyses was that most relations with structure and policy were weak or non-existent. The final multivariate model explained only 15% of the variance. The large differences between municipalities makes it more appropriate to talk about a multitude of ‘welfare municipalities’ rather than one single welfare state. The article concludes that this municipal disparity constitutes a greater threat to the principle of equality in care of the elderly than gender and socio-economic differences.

Notes: This paper investigates job-related distress and satisfaction with the work--family interface in various combinations of professional work and family responsibilities in Sweden. The study is based on the self-reports of 1,764 male and female university graduates in paid employment and with children at home. For both women and men, conditions at work seem to be most important. However, the division of responsibilities between partners was also found to have an impact, but in different ways for women and men. Only in families where both partners are gainfully employed and share the domestic work and financial responsibilities, was the psychological well-being and the work--family interface satisfactory for both women and men. In other families, negative effects for either women or men are noticed. The conclusion is that multiple roles and shared responsibilities and demands in the private sphere promote health among both women and men.

Notes: By statistical analysis of client data it is shown how past or current network information together with other knowledge assesses treatment needs. The main findings are as follows. The client’s previous exposure to addicts in the family has almost no influence on his or her present contacts with addicts in daily life. About 30% of the clients have experienced addicts both in family and among friends, about 30% have only family exposure, about 20% have neither kind of exposure, and about 20% have no family exposure but have current exposure to addicts. Exposure to addicts in family implies a higher risk of severe need for professional intervention than no such exposure. For the clients with no family exposure but with current exposure to addicts there is, somewhat surprisingly, a lower risk than for the other three categories of clients. This effect seems to be mainly because the psychiatric status of these clients is somewhat better than for those in the other three categories. The effect disappears if we look solely for drug addiction intervention needs; then there is a clear increase in relative treatment needs for the categories with previous or present addiction exposure compared to those without.

Notes: Book reviewed:Katherine A. Kendall Social work education. Its origins in Europe

Notes: The economic crisis that broke out in Korea in December 1997 has had a chilling impact on social development in the country. Today unemployment is the highest that Korea has experienced in the past thirty years. This paper aims to examine the impact of the economic crisis on social development and the role of public policy to mitigate the problems caused by the crisis. The economic crisis has hit vulnerable groups harder, increased the proportion of part-time and daily workers, and reversed the trend of steady improvement of income distribution. The economic crisis along with the trend of aging population, globalization, and competition calls for an expanded role of social policy, which the Korean government has neglected for a long time. The main targets of social policy reform in Korea include the expansion of government programs and safety nets for the unemployed and redesigning the national pension and health insurance scheme to provide adequate income security as well as to improve the system sustainability.

Notes: A mini-symposium series of papers presenting the results of the European Commission-supported Biomed II project is introduced. The project accomplished a cross-border scientific networking engaging 31 European residential treatment programmes. The results showed that scientific development is best served by a flexible bureaucratic approach. ‘Old’ science and the ‘new’ science ways of working were balanced. ‘History’ and ‘social networks’ are the key concepts signalling the project knowledge gains. A treatment sample (N=723) was extracted from a database of 1028 current European cases. Non-drug-specific characteristics are as important as drug-specific characteristics in distinguishing emerging dependence groups. The project networking created a process that increased the level of involvement of science and the service communities. To sustain the gains of the project, a reaching out of existing European treatment services to extended family and friendship networks with a history of dependence-related problems will be required.

Notes: This article describes the different phases of the development and implementation of the Videotaped Addiction Challenge Tool (VACT, initially termed the Video Addiction Challenge Test). This instrument employs a video depicting the `average life-story' of a resident of a Therapeutic Community for substance abusers. The video film is used as a clinical method for assessment and individual treatment planning, and as a research instrument that gives care-givers a deeper insight into the residents' personal characteristics and treatment requirements at any given moment in the Therapeutic Community.The article reports the results of administering the VACT to 38 residents (31 male and 7 female) at the De Kiem Therapeutic Community in Belgium. Detailed description of the procedure and its principles assures reliability and makes accurate reproduction possible. The validity of the instrument was tested by comparing, characteristic by characteristic, the results of the VACT, life-story and social anamnesis. The correspondence between the VACT and the life-story was 94% and between the VACT and the social anamnesis, 98%. The VACT has also contributed new information not measured by other instruments. Content analysis of this information shows that TC residents are characterised by negative communication between parents, negative communication with father, an unhappy childhood, child maltreatment or abuse, and relational problems due to drug abuse. Residents reported feelings of inferiority and suicidal thoughts and/or suicide attempts. Many new residents also reported sexually related problems such as abortion, sexual abuse, prostitution and shyness. There were no specific female problems; men reported sexual abuse as often as women. The implementation of this new instrument leads to a more methodical approach. It is, however, also more time-consuming and can be a problem for staff who tend to give priority to immediate action and direct problem-solving.

Notes: The purpose of this paper is to determine which theory best explains the development of social insurance programs. The survival analyses of 4 social insurance programs in 18 OECD countries present mixed results. The adoption of each social insurance program is developed and related to a combination of industrialism, modernization, left-wing participation, state autonomy, and international environment. Based on these findings, it is concluded that no single paradigm adequately explains the adoption of each of the social insurance programs. However, the combination of two society-centered approaches – namely, logic of industrialism and political conflict explanation – and a state-centered approach better explains the origin and development of modern social policy than does the international diffusion theory.

Notes: We have investigated in vivo the change with age of various parameters that describe the physical properties of skin. The parameters were derived from pressure/displacement curves obtained by applying reduced pressure to a small area of skin and measuring the resulting displacement by 20 MHz scan echography. By fitting the pressure/displacement curves to a theoretical model, the following skin parameters were obtained: E, Young's modulus or stiffness (in Pascals); σ0, the initial stress (in Pascals); and the unrestored energy ratio (UER), an index related to cutaneous non-elasticity. These parameters, which are used in mechanics to define the intrinsic physical characteristics of materials, were measured for the first time on volar forearm skin of 206 male and female subjects, aged between 6 months and 90 years.The results showed that skin thickness increases until maturity and decreases for women over 50–60 years old, Young's modulus E increases linearly with age, and ageing is divided into two phases for natural stress, σ0 and the non-elasticity index UER. Natural stress σ0 increases until maturity and then rapidly decreases. The non-elasticity index decreases until puberty and steadily increases after puberty.This new procedure provides a simple quantitative assessment of the physical properties of the skin, revealing that the skin becomes thinner, stiffer, less tense and elastic with ageing.

Notes: La méthode décrit le dosage de l′octyl dimethyl PABA (2-ethylhexyl 4-(dimethylamino)benzoate) (CAS RN 21245-02-3), de l′homo-salate (3,3,5-trimethylcyclohexyl salicylate) (CAS RN 118-56-9) et de l′octyl salicylate (2-ethylhexyl salicylate) (CAS RN 118-60-5) dans les produits cosmétiques de protection solaire.L′échantillon est mis en suspension dans le méthanol et après traitement approprié, le dosage est effectué par HPLC/UV. La précision, le rendement et la fiabilité de la méthode ont été déterminés.

Notes: Gas chromatography coupled with mass spectrometry and protonic nuclear magnetic resonance used directly or on fractions obtained by preparative thin layer chromatography, allow identification of the main molecule in commercial samples of PABA (Cas RN 150-13-0), PEG-25 PABA (Cas RN 116242-27-4), glyceryl PABA (Cas RN136-44-7), ethyl dihydroxypropyl PABA (Cas RN 58882-17-0) or octyl dimethyl PABA (Cas RN 21245-02-3).

Notes: Synopsis The effect of reaction conditions on the yield of enzymatic hydrolysis of short cattle tendons was examined using statistical scheme of factorial experiments 24. The duration of enzymatic purification of the starting material and of purified material denaturation processes, the protease concentration in reaction mixture and hydrolysis time were considered to be the main sources of reaction yield variation. An attempt was made to find the conditions leading to maximal yield of collagen hydrolysate.

Notes: After testing several chromatographic systems described in the literature, the optimal operating conditions were retained to develop a simple and rapid method grouping TLC and HPLC/UV for separation, identification and dosage of kojic acid (CAS RN 501-30-4) or arbutine (CAS RN 497-76-7) in skin-whitening cosmetic products. The screening is carried out by TLC on cellulose plate and by TLC on silicagel plate with UV indicator and polar mobile solvent. Regarding identification and quantitative determination by HPLC/UV, the best results were obtained by direct phase chromatography, using a polar stationary phase greffed with diol groups and a polar buffered mobile phase at PH 2,5.Intralaboratory prevalidation tests were carried out on the HPLC method: detection limit, linearity and intralaboratory repeatability of standard curves and repeatability of samples quantitative determination.

Notes: Synopsis Solid lipid nanoparticles (SLN) have been introduced as a novel carrier system for drugs and cosmetics. It has been found that SLN possess characteristics of physical UV-blockers on their own, thus offering the possibility of developing a more effective sunscreen system with reduced side-effects. Incorporation of the chemical sunscreen tocopherol acetate into SLN prevents chemical degradation and increases the UV-blocking capacity. Aqueous SLN dispersions were produced and incorporated into gels, followed by particle size examination, stability testing upon storage and thermoanalytical examination. Investigation of the UV-blocking capacity using different in vitro techniques revealed that the SLN dispersions produced in this study are at least twice as effective as their reference emulsions (conventional emulsions with identical lipid content). Placebo SLN even show greater UV-blocking efficacy than emulsions containing tocopherol acetate as the molecular sunscreen. Incorporation of tocopherol acetate into SLN leads to an overadditive UV-blocking effect. Furthermore, film formation of SLN on the skin and occlusivity were examined. The obtained data show that incorporation of tocopherol acetate into SLN leads to an improved sunscreen and skin care formulation.

Notes: Synopsis The scanning electron microscope (SEM) was successfully used to study the effects of toiletry treatment with shampoo on the microstructure of hair. This paper describes the use of SEM for comparing the conditioning effects of herbal shampoos.Commercially available herbal shampoos are not completely natural, but contain herbal extracts in a synthetic detergent base, along with other chemical additives. Completely natural shampoos were formulated in the laboratory and their conditioning effects were evaluated by comparing with a commercially available herbal shampoo. The micrographs were studied quantitatively using ‘Image Analyser Software’ and the extent to which the hair scales were uplifted was measured. The results obtained from the quantitative comparison were in agreement with those obtained from other tests, such as protein loss determination.The damage caused to the hair due to sodium lauryl sulphate was visible in the micrographs. The laboratory formulations were found to be better than the commercially available product. Thus, quantitative measurements from SEM micrographs are a valuable tool to compare the conditioning effects of hair care products. Résumé Le microscope electronique balayant (SEM) est appliqué avec succès a étudier les effets de traitments hygiéniques par shampooing sur le microstucture de cheveux. L’éxposé présent signale l’emploi de SEM a comparer l’effet conditionant des shampoing naturelle (herbacé).Les shampooing herbal de commerce ne sont pas totalement naturelle mais contient extrait de herbe medicinale melangés avec une base de détergent synthetique et d’autres produits chimiques; donc shampooing totalement naturelle a eté formulés dans laboratoire et leurs effets conditionant evalués en comparant avec shampooing herbal (naturelle) de commerce. Les micrographs étaient étudiés quantitativement utilisant ‘Image Analyser Software’ en mesurant le degré de relèvement de écailes des cheveux. Les résultats obtenues par comparison quantitative sont en accord avec ceux obtenues par d’autres éprevues comme perte de protéine.Le dommage causé aux cheveux par SLS est visible dans les micrographs. Les formulations de laboratoire étaient trouvés meilleurs en comparant avec les produits de commerce. Donc le measure quantitative des micrographs SEM est un outil valable a comparer les effets conditionant de produits hygienique pour cheveux.

Notes: Surface structure and surface mechanical properties of human hair have been characterized by atomic force microscopy in the imaging mode and by force vs. distance, F-d, analysis. The effects of treatment by commercial conditioner/shampoo or by aqueous exposure have been investigated. The cuticular structure has been imaged at medium resolution; longitudinal striations with lateral spacings of 150–350 nm and vertical corrugations in the range 2–8 nm were observed at higher resolution. The features are similar to those observed for untreated wool fibre. Both adventitious debris/contamination and residues from cosmetic treatment can be imaged with resolution in the low-nanometre range. Removal of the cuticular surface layer from treatment with alkali solution, and subsequent imaging, revealed a fibrous substructure. F-d analysis of the surface is a rich source of spatially resolved mechanical and chemical information. Surface stiffness, and an equivalent Young's Modulus, E, can be inferred from the shape of the ‘approach’ tip-to-surface contact curve. A value of E of ≈ 10 MPa was obtained for untreated hair. During aqueous exposure for 1 h the stiffness and modulus decreased by approximately a factor of 10. The discontinuity seen at ‘lift-off’ during the retract half-cycle of F-d analysis represents a measure of tip-to-surface adhesion. Adhesion decreased during aqueous exposure and was below the level of detectability after 1 h. Likewise, treatment by conditioner had the effect of lowering adhesion. High resolution F-d data revealed features that are consistent with the presence of a thin and readily compressible surface layer, probably analogous to the surface lipid layer on untreated wool fibre.

Notes: Synopsis The dry skin appearance of the legs is a common complaint in winter. We studied such a condition using a multi-pronged approach combining video recording under ultraviolet light, cyanoacrylate skin surface stripping and squamometry X. Two main distinct patterns of alteration of the skin surface were identified. Flexural xerosis corresponded to cracking in parallel primary lines of the stratum corneum. Accretive xerosis referred to hyperkeratosis of the plateaux delineated by the criss-cross pattern of the skin surface creases. Two distinct commercially available formulations aiming to treat dry skin yielded almost similar efficacy. For both products, flexural xerosis responded more rapidly than accretive xerosis. Résumé L’aspect de peau sèche des jambes est une situation fréquente en hiver. Nous l’avons étudiée par une approche diversifiée combinant l’examen par video en lumière ultraviolette, la biopsie de surface au cyanoacrylate et la squamométrie X. Deux types principaux et distincts d’altérations de la couche cornée ont été identifiés. La xérose flexurale correspond à la fracture de la couche cornée dans des lignes primaires orientées parallèlement les unes aux autres. La xérose par accumulation désigne l’hyperkératose des plateaux délimités par le réseau des lignes primaires. Deux formulations pour peaux sèches disponibles sur le marché ont apporté des résultats bénéfiques comparables. Pour les deux produits, la xérose flexurale a répondu plus rapidement que la xérose d’accumulation.

Notes: Synopsis Temperature, fragrance concentration on the skin and power of ventilation have been determined as crucial parameters in fragrance diffusion from skin. A tool has been developed to simulate perfume diffusion from skin over time, allowing headspace analysis and fragrance profile assessments in a highly reproducible way. Résumé La température, la concentration du parfum sur la peau et la puissance de ventilation ont été déterminées comme étant des paramètres primordiaux de la diffusion du parfum à partir de la peau. Un outil a été développé pour simuler la diffusion du parfum à partir de la peau dans le temps, permettant l’analyse headspace et des évaluations de profil de parfum de façon tout à fait reproductible.