bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of the reactive cysteine residues in oligopeptidase B from Trypanosoma brucei
Authors: Morty Rory E. , Shih Angela Y. , Fülöp Vilmos , Andrews Norma W.
Published: March 2005

Oligopeptidase B (OpdB) from Trypanosoma brucei is a candidate therapeutic target in African trypanosomiasis. OpdB is an atypical serine peptidase, since activity is inhibited by thiol‐blocking reagents and enhanced by reducing agents. We have identified C256 as the reactive cysteine residue that mediates OpdB inhibition by N‐ethylmaleimide and iodoacetic acid. Modeling studies suggest that C256 adducts occlude the P1 substrate‐binding site, preventing substrate binding. We further demonstrate that C559 and C597 are responsible for the thiol‐enhancement of OpdB activity. These studies may facilitate the development of specific OpdB inhibitors with therapeutic potential, by exploiting these unique properties of this enzyme.
An initial strategy for the systematic identification of functional elements in the human genome by low-redundancy comparative sequencing
Authors: Margulies Elliott H. , Vinson Jade P. ,   NISC Comparative Sequencing Program¶, Miller Webb , Jaffe David B. , Lindblad-Toh Kerstin , Chang Jean L. , Green Eric D. , Lander Eric S. , Mullikin James C. , Clamp Michele
Published: March 2005

With the recent completion of a high-quality sequence of the human genome, the challenge is now to understand the functional elements that it encodes. Comparative genomic analysis offers a powerful approach for finding such elements by identifying sequences that have been highly conserved during evolution. Here, we propose an initial strategy for detecting such regions by generating low-redundancy sequence from a collection of 16 eutherian mammals, beyond the 7 for which genome sequence data are already available. We show that such sequence can be accurately aligned to the human genome and used to identify most of the highly conserved regions. Although not a long-term substitute for generating high-quality genomic sequences from many mammalian species, this strategy represents a practical initial approach for rapidly annotating the most evolutionarily conserved sequences in the human genome, providing a key resource for the systematic study of human genome function.
Population
Authors: Lane Jan‐Erik , McKay David , Newton Kenneth
Published: March 2005

This section presents population data on OECD countries. It features tables on mid-year estimates, population growth, population density, age structure, birth rate, life expectancy, infant mortality rates, and urban concentration.
Employment
Authors: Lane Jan‐Erik , McKay David , Newton Kenneth
Published: March 2005

This section presents employment statistics on OECD countries. It features tables on labour force, employment by sectors, armed forces, producers of government services, government employment, unemployment, and industrial disputes.
Political Parties and Elections
Authors: Lane Jan‐Erik , McKay David , Newton Kenneth
Published: March 2005

This section presents statistics on political parties and elections in OECD countries. It features tables on national election participation, political parties, electoral strength of parties, number of parties in parliament, and electoral volatility in national elections.
Electoral Choice and the 2001 Campaign
Authors: Clarke Harold D. , Sanders David , Stewart Marianne C. , Whiteley Paul
Published: March 2005

Considers the impact of the 2001 election campaign. Contrary to what is commonly assumed about the function of election campaigns, data from the 2001 BES rolling campaign panel survey show that the 2001 campaign did little to mobilize political interest or partisanship. However, the local campaigns, conducted by party activists, contributed significantly to turnout and party choice. Analyses also indicate that tactical voting typically did not occur spontaneously but, rather, was driven by Liberal Democrat grassroots campaigning. More generally, campaigning by all of the major parties affected the vote shares that they received.
The Economy of Esteem
Authors: Brennan Geoffrey , Pettit Philip
Published: March 2005

However much people want esteem, it is an untradeable commodity: there is no way that I can buy the good opinion of another or sell to others my good opinion of them. But though it is a non-tradable good, esteem is allocated in society according to systematic determinants; people’s performance, publicity and presentation relative to others will help fix how much esteem they enjoy and how much disesteem they avoid. The fact that it is subject to such determinants means in turn that rational individuals are bound to compete with one another, however tacitly, in the attempt to control those influences, increasing their chances of winning esteem and avoiding disesteem. And the fact that they all compete for esteem in this way shapes the environment in which they each pursue the good, setting relevant comparators and benchmarks, and determining the cost that a person must bear–the price that they must pay–for obtaining a given level of esteem in any domain of activity.

Hidden in the multifarious interactions and exchanges of social life, then, there is a quiet force at work–a force as silent and powerful as gravity–which moulds the basic form of people’s relationships and associations. This force was more or less routinely invoked in the writings of classical theorists like Aristotle and Plato, Locke and Montesquieu, Mandeville and Hume and Madison. Sometimes it was invoked to explain why people behaved as they did, sometimes to identify initiatives whereby they might be persuaded to behave better. Although Adam Smith himself gave it great credence, however, the rise of economics proper coincided with a sudden decline in the attention devoted to the economy of esteem. What had been a topic of compelling interest for earlier authors fell into relative neglect throughout the nineteenth and twentieth centuries. This book is designed to reverse the trend. It begins by outlining the psychology of esteem and the way the working of that psychology can give rise to an economy. It then shows how a variety of social patterns that are otherwise anomalous come to make a lot of sense within an economics of esteem. And it looks, finally, at the ways in which the economy of esteem may be reshaped so as to make for an improvement–by reference to received criteria–in overall social outcomes. While making connections with older patterns of social theorizing, it offers a novel orientation for contemporary thought about how society works and how it may be made to work. It puts the economy of esteem firmly on the agenda of economic and social science and of moral and political theory.
9 Publicity and Accepted Standards
Authors: Brennan Geoffrey , Pettit Philip
Published: March 2005

One possible effect of increased publicity for performance is on public perceptions of prevailing standards–and this effect will intensify or moderate esteem incentives. As a result, providers of information who wish to preserve high performance may have incentives to withhold certain kinds of information or to distort the information they do provide–and sometimes such withholding/distortion has desirable consequences. This complication may give rise to a certain kind of legitimate public hypocrisy. The normative implications of information provision are explored under the rubric of the ‘whistle-blower’s dilemma’.
11 Voluntary Associations
Authors: Brennan Geoffrey , Pettit Philip
Published: March 2005

Although esteem cannot readily be the object of direct exchange, something rather like exchange can be secured in the economy of esteem via associations. By being ‘associated’ with B, A can earn ‘borrowed glory’ from B–and vice versa. The associations that so form may be very loose: all that is required is for the individuals to be associated in some esteem relevant way. The set of all Nobel Laureates is an association in this sense. An important feature of the advantages of association here is the presence of ‘economies of scale’ in publicity. One such scale effect relates to the ‘teleological paradox’: blowing the trumpet of a group of which I am a member is much less disestimable than blowing one’s own trumpet! But stronger forms of association–what we call ‘groups’–can serve the additional function of creating superior audiences for members. If the esteem of those highly esteemed is worth more, then high esteem individuals will tend to coalesce in ‘mutual admiration societies’. We discuss the optimal size and composition of groups and associations–emphasizing the hierarchical tendencies of the structure, that is, the most esteemed will tend to band together; then the next most esteemed; and so on. We suggest reasons why esteem groups and associations may be especially good at solving natural free-rider problems.
Conclusion: Co‐ordinating National Action in Brussels—a Comparative Perspective
Authors: Kassim Hussein , Peters B. Guy
Published: March 2005

This concluding chapter addresses the main issues raised in the Introduction and presents the general findings that emerge from the country studies. It has three main aims. First, it puts forward three arguments on the basis of the national investigations of policy co-ordination at the European level, and comparisons of permanent representations: the first argument is that that all the member states have responded to the co-ordination need that arises from EU policy-making and most aspire to a careful crafting of policy, but that the nature of their response varies according to the prevailing national attitude to European integration, features of the national political and administrative opportunity structures, policy style, and available resources; the second argument is that, although there are some similarities between national arrangements with respect to some aspects of organization and core functions, there are also several very substantial differences—neither the ‘convergence hypothesis’ nor the ‘continuing divergence hypothesis’ outlined in the Introduction is confirmed by the case studies, but there is evidence that many of the factors identified by each are at work; the third argument is related to effectiveness—each set of national arrangements has its own particular strengths and weaknesses, but one common factor affecting performance is the efficiency of domestic co-ordination procedures. The second aim of the Conclusion is to consider the wider implications of the findings both for the functioning of the European Union as a system and for theorizing about the EU; with respect to the former, national arrangements in Brussels do little to overcome the problem of segmentation that characterizes the EU, but concerning the latter, the case studies suggest that the intergovernmentalist image is at odds with how national policy preferences are actually formed and the nature of the role played by the permanent representations; the alternative image approach outlined above, and described in the Introduction, offers a better guide on both counts. The third and final aim of the chapter is to compare national co-ordination practices at the domestic level with those found at the European level; the contention put forward is that the domestic co-ordination of EU policy is more effective than processes at the European level.
Paradoxical Emotion: OnSui GenerisEmotional Irrationality
Authors: de Sousa Ronald
Published: March 2005

Weakness of will violates practical rationality; but may also be viewed as an epistemic failing. Conflicts between strategic and epistemic rationality suggest that we need a superordinate standard to arbitrate between them. Contends that such a standard is to be found at the axiological level, apprehended by emotions. Axiological rationality is sui generis, reducible to neither the strategic nor the epistemic. But, emotions are themselves capable of raising paradoxes and antinomies, particularly when the principles they embody involve temporality. They constitute an ultimate court of appeal, yet their biological origin allows little hope that these antinomies can be resolved.
Changes in Intergenerational Class Mobility in Hungary, 1973–2000
Authors: Róbert Péter , Bukodi Erzsébet
Published: March 2005

Investigates temporal changes in Hungarian mobility patterns. Large-scale data sets of the Hungarian Central Statistical Office, collected between 1973 and 2000 are used for this purpose. In addition to descriptive statistics, log-linear and log-multiplicative models are fitted to the data in order to investigate trends of temporal changes. Descriptive results indicate that the restructuring of the class distribution slowed down in the 1980s in comparison to the 1970s but it increased again in the 1990s. Observed mobility rates turned out to be relatively high but data does not indicate an increase in the openness of the Hungarian society. For relative mobility rates, the hypothesis of constant social fluidity cannot be rejected for Hungary. Though an increase in social fluidity did occur between 1973 and 1983, it levelled off between 1983 and 1992, and it reversed between 1992 and 2000.
Recent Trends in Intergenerational Occupational Class Reproduction in the Netherlands 1970–99
Authors: Ganzeboom Harry B. G. , Luijkx Ruud
Published: March 2005

The Netherlands has moved from being a comparatively closed society in the 1950s towards a relatively open one around 2000. Analysing occupational class mobility for men and for women in the labour force between 1970 and 1999 on the basis of 35 surveys, a clear downward trend in total social reproduction is found for men (–1.6% per year) and for women (–1.1%). No convincing evidence of a trend reversal has been found. This general trend towards more social fluidity is also replicated in the partial analysis, where the trends towards more openness do not only apply to the ascriptive parts of the status attainment patterns (fathers promoting their children’s educational and occupational outcomes directly), but also to the achievement part (the partial association between education and occupation). The last finding contradicts common theories. A possible explanation is that, over time, educational credentials have lost some of their discriminatory power.
Modern Challenges to the Welfare State and the Antecedents of the Third Way
Authors: Surender Rebecca
Published: March 2005

There has been considerable rethinking on the part of governments when it comes to social policy, in particular, about the relationships between the labour market, the family, and the state, and about the role of the state and the nature of governance. Very little of the post-war welfare settlement remains unquestioned, whether the nature of the risk addressed; the nature of entitlements and the form of conditionality to be applied; or the best means of making provision. This chapter outlines these welfare state changes and discusses possible explanations for them including political pragmatism, rapid structural change and the role of political ideas. It argues that whether referred to as ‘Third Way’ or not, many similarities in the welfare reforms adopted by industrialized welfare states can be identified. The chapter offers an examination of the US, the UK, and Australian cases to argue that in order to understand why an explicit discourse of policy reconfiguration and reform was actively embraced in some countries but avoided in others, an analysis of the impact of both the political history and constraints of institutional structures is necessary.
Welfare Philosophy and the Third Way
Authors: White Stuart
Published: March 2005

Critics of the Third Way in welfare argue that it represents a break with the philosophy of the welfare state characteristic of mainstream social democracy. They argue that the Third Way is not genuinely egalitarian. They argue that it embodies ideas about personal responsibility and social duty that are incompatible with a social democratic commitment to a welfare state founded on ‘social rights’. This paper considers these claims. It argues that central Third Way claims about the balancing of rights and responsibilities do in fact fit with the mainstream traditions of social democratic welfare philosophy. However, Third Way thinkers do indeed aspire to a much less ambitious kind of egalitarianism than was aspired to by past generations of social democratic thinkers.
A Race to the Bottom?
Authors: Castles Francis G.
Published: March 2005

This chapter focuses on the argument that recent years have seen a ‘race to the bottom’ in social spending. Using comparative data from 21 OECD countries, it shows that social spending has been increasing rather than decreasing in recent decades and that the welfare state has become a more prominent aspect of public policy in most OECD countries. The chapter also shows that adjustments to take account of standards of provision and real spending per capita do not fundamentally alter this picture.
Risk/Benefit Assessments of Human Diseases: Optimum Dose for Intervention
Authors: Gaylor David W.
Published: March 2005

A simple procedure is proposed in order to quantify the tradeoff between a loss suffered from an illness due to exposure to a microbial pathogen and a loss due to a toxic effect, perhaps a different illness, induced by a disinfectant employed to reduce the microbial exposure. Estimates of these two types of risk as a function of disinfectant dose and their associated relative losses provide information for the estimation of the optimum dose of disinfectant that minimizes the total expected loss. The estimates of the optimum dose and expected relative total loss were similar regardless of whether the beta‐Poisson, log‐logistic, or extreme value function was used to model the risk of illness due to exposure to a microbial pathogen. This is because the optimum dose of the disinfectant and resultant expected minimum loss depend upon the estimated slope (first derivative) of the models at low levels of risk, which appear to be similar for these three models at low levels of risk. Similarly, the choice among these three models does not appear critical for estimating the slope at low levels of risk for the toxic effect induced by the use of a disinfectant. For the proposed procedure to estimate the optimum disinfectant dose, it is not necessary to have absolute values for the losses due to microbial‐induced or disinfectant‐induced illness, but only relative losses are required. All aspects of the problem are amenable to sensitivity analyses. The issue of risk/benefit tradeoffs, more appropriately called risk/risk tradeoffs, does not appear to be an insurmountable problem.
A New Look at the Psychometric Paradigm of Perception of Hazards
Authors: Siegrist Michael , Keller Carmen , Kiers Henk A. L.
Published: March 2005

The psychometric paradigm has been the most influential model in the field of risk analysis. The “cognitive maps” of hazards produced by the paradigm seem to explain how laypeople perceive the various risks they face. Because most of the studies used aggregated data, analyzed using principal component analysis, it is not known whether the model neglects individual differences in risk perception. There has been much criticism on the fact that few studies have examined individual differences in the cognitive representation of hazards. In order to detect and describe the internal structure of the three‐way data, we conducted a three‐way component analysis (3MPCA). Data for the present analysis were derived from a mail survey conducted in Switzerland. Participants were asked to judge 9 attributes for 26 hazards. Individual differences in the cognitive representation of hazards were correlated with external variables (e.g., general trust). The results suggest that methods permitting individual differences should be used more frequently and that utilizing different methods could provide greater insight into the cognitive representation of risks.
Mommy and Me
Authors: Bortfeld Heather , Morgan James L. , Golinkoff Roberta Michnick , Rathbun Karen
Published: March 2005

How do infants find the words in the tangle of speech that confronts them? The present study shows that by as early as 6 months of age, infants can already exploit highly familiar words—including, but not limited to, their own names—to segment and recognize adjoining, previously unfamiliar words from fluent speech. The head-turn preference procedure was used to familiarize babies with short passages in which a novel word was preceded by a familiar or a novel name. At test, babies recognized the word that followed the familiar name, but not the word that followed the novel name. This is the youngest age at which infants have been shown capable of segmenting fluent speech. Young infants have a powerful aid available to them for cracking the speech code. Their emerging familiarity with particular words, such as their own and other people's names, can provide initial anchors in the speech stream.
Measuring EGJ opening patterns using high resolution intraluminal impedance
Authors: Pandolfino J. E. , Shi G. , Zhang Q. , Ghosh S. , Brasseur J. G. , Kahrilas P. J.
Published: March 2005

Abstract  The aim of this study was to adapt impedance methodology to study esophagogastric junction (EGJ) sphincter opening and compare opening patterns of the EGJ during deglutitive LES relaxation (dLESR) and transient LES relaxation (tLESR). We studied eight healthy subjects with a novel 12‐lumen combined impedance/manometry catheter, the main element of which was a 6 cm sleeve sensor with six side hole sensors and six impedance rings spaced at 1 cm increments along its length. Subjects underwent an air infusion protocol after standard assessment and data tracings and isocontour plots were analysed to assess opening characteristics of the EGJ during dLESRs and tLESRs. Our results revealed that during dLESR the opening pattern was top to bottom, occurred in 0–2.7 s and in 29 of 35 (83%) cases the leading edge of the bolus was liquid. Opening during tLESR began between −7.8 and +8.6 s relative to the onset of nadir LES relaxation. The opening pattern during tLESR was bottom to top, occurred in 0–7.7 s, and in 22 of 29 (76%) the leading edge was liquid. These results support that impedance monitoring can be adapted to identify sphincter opening, to distinguish sphincter opening from sphincter relaxation, and to determine luminal contents during the opening period.
Targeting cerebral arteries for gene therapy
Authors: Watanabe Yoshimasa , Heistad Donald D.
Published: March 2005

After the steady progress towards application of gene therapy to cerebral arterial diseases, several applications, including modification of gene expression in cerebral arteries, are now feasible. There are several possible targets for cerebrovascular gene therapy, and numerous studies have tested gene therapy strategies in animal models of cerebrovascular disorders. However, some major obstacles, especially issues of safety, must be overcome before clinical use in humans. Gene therapy for cerebral arterial diseases is still in its infancy, and many basic and preclinical studies are yet to be done in order to develop effective and safe techniques.
Low pressure ultraviolet inactivation of pathogenic enteric viruses and bacteriophages
Authors: Shin Gwy-Am , Linden Karl G , Sobsey Mark D
Published: March 2005

To elucidate the roles of physical and chemical properties of viruses and their sensitivity to UV radiation, the kinetics and extent of inactivation of several waterborne pathogenic viruses and bacteriophages with different virion sizes and genomic composition by monochromatic, low-pressure (LP) UV was determined in phosphate buffered saline or a filtered drinking water. The inactivation rates of the small RNA viruses, poliovirus 1 and Coxsackievirus B4, by LP UV were very rapid and reached ~4 log10 and >5 log10, respectively, within a UV dose of 30 mJ/cm2. In contrast, the inactivation of the small RNA bacteriophage, MS2, was much slower and only 2 log10 inactivation was achieved at a UV dose of 30 mJ/cm2. The inactivation of the large DNA virus, adenovirus 2, was relatively slow and only 2 log10 inactivation was achieved with a UV dose of 60 mJ/cm2. In contrast, the inactivation rates of the three large DNA bacteriophages were very rapid and reached >5 log10 with a UV dose of 10 mJ/cm2. Therefore, the results of this study indicate that inactivation of human enteric viruses and bacteriophages by UV irradiation is not simply predictable by the type and size of the virus or its nucleic acid genome and there is no strong correlation between virion size and genetic composition of enteric viruses and their response to LP UV irradiation. Key words: low pressure ultraviolet (LP UV), poliovirus 1, Coxsackievirus B4, bacteriophage MS2, bacteriophage PRD1, adenovirus 2, UV disinfection.
Combined electrochemical degradation and activated carbon adsorption treatments for wastewater containing mixed phenolic compounds
Authors: Rajkumar D , Palanivelu K , Balasubramanian N
Published: March 2005

Electrochemical degradation of mixed phenolic compounds present in coal conversion wastewater was investigated in the presence of chloride as supporting electrolyte. Initially, the degradation experiments were conducted separately with 300 mg/L of individual phenolic compound in the presence of 2500 mg/L chloride using Ti/TiO2RuO2IrO2 anode at 5.4 A/dm2 current density. Comparison of the experimental results of the chemical oxygen demand (COD) removal versus charge indicated that the order of decreasing COD removal for various phenolic compounds as catechol > resorcinol > m-cresol > o-cresol > phenol > p-cresol. Degradation of the mixture of phenolic compounds and high-pressure liquid chromatography (HPLC) determinations at various stages of electrolysis showed that phenolic compounds were initially converted into benzoquinone and then to lower molecular weight aliphatic compounds. The COD and the total organic carbon (TOC) removal were 83 and 58.9% after passing 32 Ah/L with energy consumption of 191.6 kWh/kg of COD removal. Experiments were also conducted to remove adsorbable organic halogens (AOX) content in the treated solution using granular activated carbon. The optimum conditions for the removal of AOX was at pH 3.0, 5 mL/min flow rate and 31.2 cm bed height. Based on the investigation, a general scheme of treatment of mixed phenolic compounds by combined electrochemical and activated carbon adsorption treatment is proposed.Key words: electrochemical degradation, phenolic compounds, chemical oxygen demand, total organic carbon, adsorbable organic halides, activated carbon adsorption.
The Catastrophic Flash-Flood Event of 8–9 September 2002 in the Gard Region, France: A First Case Study for the Cévennes–Vivarais Mediterranean Hydrometeorological Observatory
Authors: Delrieu Guy , Nicol John , Yates Eddy , Kirstetter Pierre-Emmanuel , Creutin Jean-Dominique , Anquetin Sandrine , Obled Charles , Saulnier Georges-Marie , Ducrocq Véronique , Gaume Eric , Payrastre Olivier , Andrieu Hervé , Ayral Pierre-Alain , Bouvier Christophe , Neppel Luc , Livet Marc , Lang Michel , du-Châtelet Jacques Parent , Walpersdorf Andrea , Wobrock Wolfram
Published: March 2005

The Cévennes–Vivarais Mediterranean Hydrometeorological Observatory (OHM-CV) is a research initiative aimed at improving the understanding and modeling of the Mediterranean intense rain events that frequently result in devastating flash floods in southern France. A primary objective is to bring together the skills of meteorologists and hydrologists, modelers and instrumentalists, researchers and practitioners, to cope with these rather unpredictable events. In line with previously published flash-flood monographs, the present paper aims at documenting the 8–9 September 2002 catastrophic event, which resulted in 24 casualties and an economic damage evaluated at 1.2 billion euros (i.e., about 1 billion U.S. dollars) in the Gard region, France. A description of the synoptic meteorological situation is first given and shows that no particular precursor indicated the imminence of such an extreme event. Then, radar and rain gauge analyses are used to assess the magnitude of the rain event, which was particularly remarkable for its spatial extent with rain amounts greater than 200 mm in 24 h over 5500 km2. The maximum values of 600–700 mm observed locally are among the highest daily records in the region. The preliminary results of the postevent hydrological investigation show that the hydrologic response of the upstream watersheds of the Gard and Vidourle Rivers is consistent with the marked space–time structure of the rain event. It is noteworthy that peak specific discharges were very high over most of the affected areas (5–10 m3 s−1 km−2) and reached locally extraordinary values of more than 20 m3 s−1 km−2. A preliminary analysis indicates contrasting hydrological behaviors that seem to be related to geomorphological factors, notably the influence of karst in part of the region. An overview of the ongoing meteorological and hydrological research projects devoted to this case study within the OHM-CV is finally presented.
Effect of the MDR1 C3435T Variant and P‐Glycoprotein Induction on Dicloxacillin Pharmacokinetics
Authors: Putnam Wendy S. , Woo Jonathan M. , Huang Yong , Benet Leslie Z.
Published: March 2005

This study investigated 2 hypotheses about genotype‐phenotype relationships for the efflux transporter, P‐glycoprotein: (1) the presence of a synonymous C3435T variant in exon 26 of the MDR1 gene correlates to higher plasma concentrations of a P‐glycoprotein substrate, dicloxacillin, and (2) the effects of genotypic differences decrease under conditions of P‐glycoprotein induction by rifampin. Eighteen healthy volunteers received two 1‐g doses of dicloxacillin, one on the 1st study day and the other on the 11th day of rifampin dosing (600 mg daily). Dicloxacillin and its 5‐hydroxymethyl metabolite were analyzed using liquid chromatography/tandem mass spectrometry. Mean dicloxacillin Cmax measurements were 30.5 ± 13.5, 33.3 ± 4.7, and 31.1 ± 12.8 μg/mL in individuals with the CC, CT, and TT genotype at position 3435 in exon 26 of the MDR1 gene. Following rifampin dosing, the mean dicloxacillin Cmax across genotypes decreased from 31.4 ± 10.8 to 22.9 ± 7.0 μg/mL (P < .05), whereas the mean oral clearance increased from 235 ± 82 to 297 ± 71 mL/min (P < .001), and the mean absorption time increased from 0.71 ± 0.55 to 1.34 ± 0.77 h (P 7< .05). Rifampin treatment increased the formation clearance, Cmax, and AUC of the 5‐hydroxymethyl metabolite by 135%, 119%, and 59%, respectively. The C3435T variant had no effect on dicloxacillin pharmacokinetics. The data suggested that rifampin induced intestinal P‐glycoprotein and increased dicloxacillin metabolism.
Creating a Confluence: An Interview With Susan Johnson and John Gottman
Authors: Young Mark A.
Published: March 2005

In 2003, The Family Journal interviewed Dr. Susan Johnson (Jencius, 2003) and Dr. John Gottman (Jencius & Duba, 2003) in individual interviews. This interview is with Drs. Johnson and Gottman together in an attempt to capture the confluence of their mutual influence. Sue Johnson is a professor of psychology and psychiatry at Ottawa University and director of the Ottawa Couple and Family Institute. She is one of the originators and the main proponent of emotionally focused couples therapy (EFT). John Gottman is co-founder of the Gottman Institute, director of the Relationship Research Institute, and emeritus professor of psychology at the University of Washington. Both have done extensive research in the areas of couple relationships, and each maintains an active research and training schedule. This interview took place in November 2003 in Seattle, Washington. For more information about the works of Johnson and Gottman, visit their Web sites at www.eft.ca and www.gottman.com.
Developmental Characteristics of Home-Based Counselors: A Key to Serving At-Risk Families
Authors: Lawson Gerard , Foster Victoria A.
Published: March 2005

Home-based counseling is an incredibly demanding intervention, yet little is known about the counselors providing this important service. This study sought to profile ego development, conceptual complexity, and supervision satisfaction for 120 home-based counselors. Counselors scored at moderate levels on measures of both ego development and conceptual level. Most counselors (74.2%) reported dissatisfaction with supervision because they are “undersupervised.” Implications for using a cognitive developmental framework for training and supervising home-based counselors are discussed.
Encore Parenting: When Grandparents Fill the Role of Primary Caregiver
Authors: Lever Karla , Wilson Jennifer J.
Published: March 2005

This literature review explores the issues of grief and the interruption of developmental stages often experienced by grandparents who raise their grandchildren and presents a case study to illustrate that structural family therapy can address and combat these issues. An evaluation of the use of structural family therapy in relation to grief and loss issues is offered.
SANCTUS Marriage Enrichment
Authors: Sager Denise E. , Sager Wilfred G.
Published: March 2005

SANCTUS is a faith-based marriage enrichment program in conference setting, with post-weekend gatherings, daily couple meditations, and exercises for individuals. Theological, educational, and psychological insights from SANCTUS originator Wilfred G. Sager, Ed.D., are presented to couples who journal and share their responses with spouses. Data gathered from SANCTUS participants in pre- and post-weekend surveys showed an average 40% improvement in relationships with God, self, and spouse.
Major Moves
Authors: Golden Larry , Duffey Thelma , Haberstroh Shane , Juhnke Gerald , Trepal Heather
Published: March 2005

When professors move to accept academic positions, there is an effect on their marriages and families. Once established in the new locations, these same professors pass through predictable stages that set them up for still further moves. Each move raises expectations of the perfect job in the perfect place. Each move also becomes more complicated. This article describes the personal experience of professors and their families.
Co-morbidity leads to altered treatment and worse survival of elderly patients with colorectal cancer
Authors: Lemmens V E P P , Janssen-Heijnen M L G , Verheij C D G W , Houterman S , Repelaer van Driel O J , Coebergh J W W
Published: March 2005

Background

The aim of this study was to evaluate the effects of co-morbidity on the treatment and prognosis of elderly patients with colorectal cancer.

Methods

The independent influence of age and co-morbidity on treatment and survival was analysed for 6931 patients with colorectal cancer aged 50 years or more diagnosed between 1995 and 2001 in the southern part of the Netherlands.

Results

Co-morbidity had no influence on resection rate. The use of adjuvant chemotherapy in patients with stage III colonic cancer was influenced by co-morbidity, especially a previous malignancy (odds ratio (OR) 0·2 (95 per cent confidence interval (c.i.) 0·1 to 0·6); P = 0·002) or chronic obstructive pulmonary disease (COPD) (OR 0·3 (95 per cent c.i. 0·1 to 0·9); P = 0·043). Co-morbidity also influenced use of adjuvant radiotherapy in patients with rectal cancer, especially the presence of hypertension in combination with diabetes (OR 0·5 (95 per cent c.i. 0·2 to 0·9); P = 0·031). Co-morbidity influenced survival (hazard ratio up to 1·6), when adjusted for age, sex, tumour stage and treatment. The greatest influence on survival of patients with colonic cancer was previous malignancy, cardiovascular disease and COPD, and that of patients with rectal cancer was COPD, hypertension, and hypertension in combination with diabetes.

Conclusion

Elderly patients with co-morbidity were treated less aggressively and had a worse survival than those with no concomitant disease.
A cohort study of cancer risk in relation to family histories of cancer in the Utah population database
Authors: Kerber Richard A. , O'Brien Elizabeth
Published: March 2005

BACKGROUND

It is well known that genetic variability affects the risk of many cancers, but details of the patterning of inherited cancer risk across different sites and age groups still are not well quantified.

METHODS

The authors conducted a nested case–control study of the familial risk of 40 cancers based on a cohort of 662,515 individuals from the Utah Population Database. From 1 to 10 controls selected from the cohort were matched individually on gender, birth year, and birthplace to each cancer case; and familial standardized incidence ratios (FSIR) were calculated for both cases and controls. Conditional logistic regression was used to estimate relative risks and population‐attributable risks (PARs) of cancer in relation to FSIR. Relative risks of cancer in first‐degree through fifth‐degree relatives of cases, compared with controls, were calculated using the proportional hazards methods. All analyses were adjusted for spouse affection status and Latter Day Saints church affiliation.

RESULTS

Thirty‐five of 40 cancers exhibited positive associations between risk and FSIR, and 21 of those associations were statistically significant. PAR estimates were strikingly high for prostate carcinoma (57%), breast carcinoma (39%), colon carcinoma (32%), lip carcinoma (31%), chronic lymphocytic leukemia (35%), and melanoma (32%). Both the proportion and the number of all cancers attributable to family history peaked at 32% in the group ages 65–84 years and remained high in the group age ≥ 85 years.

CONCLUSIONS

A substantial portion of cancer risk was attributable to familial factors. The patterns of familial cancer recurrence among distant relatives suggested that simple genetic mechanisms may explain much of the familiality of cancer. Cancer 2005. © 2005 American Cancer Society.
Flow cytometric characterization of viable meiotic and postmeiotic cells by Hoechst 33342 in mouse spermatogenesis
Authors: Bastos Henri , Lassalle Bruno , Chicheportiche Alexandra , Riou Lydia , Testart Jacques , Allemand Isabelle , Fouchet Pierre
Published: March 2005

Background

Spermatogenesis in adult is a complex stepwise process leading to terminally differentiated spermatozoa. The cellular heterogeneity of testis renders complex the studies on molecular aspects of this differentiation process. Analysis of the regulation of adult spermatogenesis would undoubtedly benefit from the development of techniques to characterize each germinal differentiation step.

Methods

Hoechst 33342 staining of mouse testicular cells allows characterization of an enriched population in germinal stem cell and spermatogonia, called side population. In this study, we examined the definition of the various germinal populations stained by Hoechst 33342, notably meiotic and postmeiotic cells.

Results

Preleptotene spermatocytes, spermatocyte I, spermatocyte II, and round and elongated spermatids were discriminated by Hoechst 33342 staining. In addition, we associated differentiation of spermatocyte I through leptotene to diplotene with changes in Hoechst 33342 red fluorescence pattern.

Conclusions

Hoechst 33342 staining of viable germinal cells constitutes a valuable tool to study normal and impaired mouse adult spermatogenesis or to isolate viable cells from various differentiation stages for studies of molecular mechanisms regulating spermatogenesis. © 2005 Wiley‐Liss, Inc.
Emerging patterns of cardiac conduction in the chick embryo: Waveform analysis with photodiode array‐based optical imaging
Authors: Rothenberg Florence , Watanabe Michiko , Eloff Benjamin , Rosenbaum David
Published: March 2005

Major difficulties investigating the developing cardiac conduction system stem from that the embryonic heart is extremely small (< 2 mm) and cardiac activation is relatively rapid (< 8 msec). The objective of this study was to investigate the electrophysiology of the embryonic chick cardiac conduction system at periseptation stages with a photodiode array‐based detection method of optical mapping capable of high spatial and temporal resolution. Previous work indicated that, in chicken embryos, a switch occurs in ventricular activation pattern from immature base‐to‐apex to mature apex‐to‐base pattern at the time of ventricular septation. It was our aim to map activation in more detail to identify the active pathway or pathways of atrioventricular conduction at these particular stages. Analysis of preseptated hearts (n = 10) showed that the latest atrial activation took place just above the site of the earliest ventricular activation at the ventral left ventricular base. Analysis of postseptated hearts (n = 11) showed apex‐to‐base conduction consistent with activation through the maturing His–Purkinje system. Evaluation of hearts during septation revealed a gradual transition of ventricular activation patterns rather than an abrupt “switch.” External pacing of preseptated hearts revealed significant slowing of interventricular conduction compared with spontaneous beats (spontaneous, 61.7 cm/sec ± 9 cm/sec vs. paced, 36.5 cm/sec ± 10 cm/sec). The more detailed mapping revealed that, before septation, the pattern of activation of the ventricular myocardium is consistent with direct atrial–ventricular myocardial connections at the left lateral atrioventricular junction; however, functional evidence for a preferential conduction pathway within the ventricles was present before septation. Developmental Dynamics 233:456–465, 2005. © 2005 Wiley‐Liss, Inc.
Downregulation of GFAP, TSP‐1, and p53 in human glioblastoma cell line, U373MG, by IE1 protein from human cytomegalovirus
Authors: Lee Karim , Jeon Kipyoung , Kim Jong‐Mook , Kim Vic Narry , Choi Dong Hee , Kim Seung U. , Kim Sunyoung
Published: March 2005

Human cytomegalovirus (HCMV) is a member of the β‐herpesvirus family, which has tropism for glial cells. It was recently reported that HCMV might play important roles in the pathogenesis of malignant glioma. In this study, we investigated the effects of the HCMV IE1 protein on the gene expression profile in the human glioblastoma cell line, U373MG by employing cDNA microarray technology. Using DNA chips containing approximately 1,000 human cDNAs, RNA samples from U373MG cells stably expressing IE1 were compared with those from the control cells lacking IE1 cDNA. Fluorescence intensities of 13 genes were significantly decreased in IE1‐expressing cells, while one gene was found to be upregulated. Among these 14 genes, we chose to work further on glial fibrillary acidic protein (GFAP), thrombospondin‐1 (TSP‐1), and p53, because of their previously known involvement in tumorigenesis. The mRNA levels of all these genes were found to be decreased in IE1‐expressing glioblastoma cells by real‐time quantitative reverse transcription‐polymerase chain reaction (RT‐PCR) as well as Northern blot analysis. The decreased expression of these genes was also observed at protein levels as measured by immunocytochemistry or fluorescence‐activated cell sorting (FACS) analysis. Our data strongly suggested that HCMV IE1 could modulate the expression of cellular genes that might play important roles in the pathogenesis of glial tumors. © 2005 Wiley‐Liss, Inc.
Very low intensity alternating current decreases cell proliferation
Authors: Cucullo Luca , Dini Gabriele , Hallene Kerri L. , Fazio Vincent , Ilkanich Erin V. , Igboechi Chiazor , Kight Kelly M. , Agarwal Mukesh K. , Garrity‐Moses Mary , Janigro Damir
Published: March 2005

Electric fields impact cellular functions by activation of ion channels or by interfering with cell membrane integrity. Ion channels can regulate cell cycle and play a role in tumorigenesis. While the cell cycle may be directly altered by ion fluxes, exposure to direct electric current of sufficient intensity may decrease tumor burden by generating chemical products, including cytotoxic molecules or heat. We report that in the absence of thermal influences, low‐frequency, low‐intensity, alternating current (AC) directly affects cell proliferation without a significant deleterious contribution to cell survival. These effects were observed in normal human cells and in brain and prostate neoplasms, but not in lung cancer. The effects of AC stimulation required a permissive role for GIRK2 (or KIR3.2) potassium channels and were mimicked by raising extracellular potassium concentrations. Cell death could be achieved at higher AC frequencies (>75 Hz) or intensities (>8.5 μA); at lower frequencies/intensities, AC stimulation did not cause apoptotic cellular changes. Our findings implicate a role for transmembrane potassium fluxes via inward rectifier channels in the regulation of cell cycle. Brain stimulators currently used for the treatment of neurological disorders may thus also be used for the treatment of brain (or other) tumors. © 2005 Wiley‐Liss, Inc.
Positive and negative depression coping in low‐income African American women
Authors: Oakley Linda Denise , Song Mi‐Kyung , DeBose‐McQuirter Michelle
Published: March 2005

The purpose of the study was to examine positive and negative depression coping (DC) in low‐income African American women. Because low‐income African American women have been shown to be vulnerable to depression symptom onset yet less accepting of treatment, DC in this population is of interest to researchers. Depression symptom severity, defense mechanisms, difficult life circumstances (DLC), and social support were examined as possible determinants of DC. In 244 mildly or moderately to severely depressed women, mature defense mechanisms predicted positive DC, and DLC predicted negative DC. Social support had no effect on positive or negative DC. Findings are discussed in terms of individual and community tailored rehabilitative psychotherapy to promote positive DC. © 2005 Wiley Periodicals, Inc. Res Nurs Health 28:106–116, 2005
Linking tumor cell cytotoxicity to mechanism of drug action: An integrated analysis of gene expression, small‐molecule screening and structural databases
Authors: Covell David G. , Wallqvist Anders , Huang Ruili , Thanki Narmada , Rabow Alfred A. , Lu Xiang‐Jun
Published: March 2005

An integrated, bioinformatic analysis of three databases comprising tumor‐cell‐based small molecule screening data, gene expression measurements, and PDB (Protein Data Bank) ligand–target structures has been developed for probing mechanism of drug action (MOA). Clustering analysis of GI50 profiles for the NCI's database of compounds screened across a panel of tumor cells (NCI60) was used to select a subset of unique cytotoxic responses for about 4000 small molecules. Drug–gene–PDB relationships for this test set were examined by correlative analysis of cytotoxic response and differential gene expression profiles within the NCI60 and structural comparisons with known ligand–target crystallographic complexes. A survey of molecular features within these compounds finds thirteen conserved Compound Classes, each class exhibiting chemical features important for interactions with a variety of biological targets. Protein targets for an additional twelve Compound Classes could be directly assigned using drug‐protein interactions observed in the crystallographic database. Results from the analysis of constitutive gene expressions established a clear connection between chemo‐resistance and overexpression of gene families associated with the extracellular matrix, cytoskeletal organization, and xenobiotic metabolism. Conversely, chemo‐sensitivity implicated overexpression of gene families involved in homeostatic functions of nucleic acid repair, aryl hydrocarbon metabolism, heat shock response, proteasome degradation and apoptosis. Correlations between chemo‐responsiveness and differential gene expressions identified chemotypes with nonselective (i.e., many) molecular targets from those likely to have selective (i.e., few) molecular targets. Applications of data mining strategies that jointly utilize tumor cell screening, genomic, and structural data are presented for hypotheses generation and identifying novel anticancer candidates. Proteins 2005. Published 2005 Wiley‐Liss, Inc.