bluuebunny/crossref_metadata_2025 huggingface dataset:
Mozart's Don Giovanni and the Invitation to Full Freedom
Authors: Casey Thomas G.
Published: April 2007

Mozart's operatic masterpiece Don Giovanni
raises pivotal questions about freedom and society: should freedom be
without constraints? Is absolute freedom possible? In certain key ways these
concerns of Mozart's culture resonate with issues that preoccupy us today.
Composed in 1787, during the final years of the liberal regime introduced by
the Habsburg emperor Joseph II, the opera reflects the shadow side of his
“enlightened” reforms. The serial seducer Don Giovanni represents a liberty
that has degenerated into libertinism. The freedom that Don Giovanni wants
to retain at all costs is merely freedom as the absence of physical
constraint. In the contemporary world many people aspire to a similarly
riven freedom: they reject the dictates of external authority, and docilely
submit to the promptings of instinctual drives. Christianity invites human
beings to reach beyond themselves in love. Marriage exemplifies the
self-giving of permanent commitment, and contrasts starkly with Don
Giovanni's egoistic consumption and hasty disposal of women. Although the
lyrics and plot of Mozart's opera never evoke the Trinity, the musical
perfection of his work dances on the threshold of Revelation, and opens its
hearers up to the liberating mystery of the freedom of Trinitarian
love.
Sacramental Ontology: Nature and the Supernatural in the Ecclesiology of
Henri de Lubac
Authors: Boersma Hans
Published: April 2007

This essay argues that for Henri de Lubac, a sacramental ontology
provides the link between a Eucharistically based ecclesiology and the issue
of the relationship between nature and the supernatural. For de Lubac it is
the sacramental order of reality that draws humanity to a deeper
participation in the divine life. Maurice Blondel's substitution of
Tradition for the dilemma between extrinsicism and historicism shapes de
Lubac's sacramental ontology. The latter's concern for the social character
of the Church and his opposition to an individualist ecclesiology are key to
his understanding of the relationship between the supernatural and the
Eucharistic character of the Church. Arguing that Eucharist and Church are
mutually constituting, de Lubac wants to counter both extrinsicist and
historicist approaches to the Church. For de Lubac, the Eucharist provides
an avenue for the mutual interpenetration of nature and the supernatural,
thereby overcoming the dualism between extrinsicism and historicism. It is
through the sacramental means of Christ, the Church, and the Eucharist, that
God is present in the world. This presence means for de Lubac neither an
acceptance of the State on its own terms nor an exaggerated spiritualist
critique of Constantinianism.
Gender Equality or Primacy of the Mother? Ambivalent Descriptions of Good Parents
Authors: Perälä‐Littunen Satu
Published: April 2007

The ideology of gender equality is accepted as the norm in the Nordic countries. When asked to describe what they thought was required to be a good mother and a good father, Finnish informants (N= 387) showed uneasiness in describing good parents separately, however, often describing only a good mother. This article aims to explore the ambivalent stance toward gender equality reflected in these descriptions. The mother is seen as the model against which the father is compared. Moreover, the ambivalence noted could indicate a contradiction between how things are and how they should be. Ambivalence here is located between structural, sociological, and psychological levels, reflects the ambivalent rhetoric of welfare officials, and is possibly the result of social change.
Women’s Employment Status, Coercive Control, and Intimate Partner Violence in Mexico
Authors: Villarreal Andrés
Published: April 2007

Findings from previous studies examining the relation between women’s employment and the risk of intimate partner violence have been mixed. Some studies find greater violence toward women who are employed, whereas others find the opposite relation or no relation at all. I propose a new framework in which a woman’s employment status and her risk of violent victimization are both influenced by the level of control exercised by her partner. Controlling men will actively prevent women from working and are also more likely to physically harm their partners. Using a statistical model in which the effect of omitted characteristics on women’s employment and their risk of violence are allowed to be correlated reverses the estimated association between employment and violence. The final results show that employment reduces women’s risk of violence. Data for the study are drawn from a sample of over 30,000 Mexican women in intimate relationships. The findings have broad implications given the increase in female labor force participation in many parts of the world.
The Influence of Grandparents in Single‐Mother Families
Authors: Dunifon Rachel , Kowaleski‐Jones Lori
Published: April 2007

This article examines whether children living with single mothers benefit when they also live with a grandparent, using data from the 1979 to 2002 waves of the National Longitudinal Survey of Youth merged mother‐child file (N = 6,501). Results indicate that for White children, living with a single mother and a grandparent is associated with increased cognitive stimulation and higher reading recognition scores, compared to living with a single mother alone. For Black children, grandparent coresidence is associated with less cognitive stimulation. Thus, in some instances, living with a grandparent can benefit children, but the pattern of results differs by race.
Income and Life Satisfaction After Marital Disruption in Germany
Authors: Andreß Hans‐Jürgen , Bröckel Miriam
Published: April 2007

Divorce in Germany and in many other countries is often instigated by the wife, even though marital disruption has much more negative economic consequences for women than for men. Both observations, however, are not necessarily a contradiction. Women may gain something that makes up for the economic loss. On the one hand, using data on income and (general) life satisfaction from the German Socio‐Economic Panel Study, this article shows that negative economic changes, as measured by data on household income, are real in the sense that they are reflected in subjective assessments of economic well‐being. On the other hand, these changes are relative because other aspects of life improve after marriage dissolution, and this is especially true for women.
Household Structure and Living Conditions in Nigeria
Authors: Mberu Blessing Uchenna
Published: April 2007

Data on 7,632 households from the 1999 Nigeria Demographic and Health Survey are used to examine household structure and living conditions in Nigeria. The study finds significant disadvantage in living conditions of single‐adult, female‐ and single‐adult, male‐headed households relative to two‐parent households. Extended households show no significant advantage in living conditions over two‐parent households if headed by women but are consistently advantaged if headed by men. Although extended households do not entirely wipe out the disadvantage of female headship on household living conditions, they show a significant mitigating potential. Efforts to understand and alleviate poverty in Nigeria may need to address simultaneously gender imbalances in access to livelihood opportunities and factors that foster nucleation of family structure into single‐adult households.
Family Structure and Child Mortality in Sub‐Saharan Africa: Cross‐National Effects of Polygyny
Authors: Omariba D. Walter Rasugu , Boyle Michael H.
Published: April 2007

This study applies multilevel logistic regression to Demographic and Health Survey data from 22 sub‐Saharan African countries to examine whether the relationship between child mortality and family structure, with a specific emphasis on polygyny, varies cross‐nationally and over time. Hypotheses were developed on the basis of competing theories on the relationship between child health and family structure. Although children of mothers in polygynous marriages are more likely to die than those of mothers in monogamous unions, the relationship is constant across time. Familial factors including education, socioeconomic status (SES), and urban residence accounted for most of the observed cross‐national variation associated with polygyny. Consequently, improving maternal education and household SES would greatly benefit child health in sub‐Saharan Africa.
The Literary Representation of Women Doctors in the United States, 1860–1920
Authors: Wegener Frederick
Published: April 2007

Literary representations of women doctors in the United States between 1860 and 1920 – the period in which women first entered the American medical profession – have become the focus of extensive critical study over the past thirty years. Much as the initial rise of American women doctors has recently attracted the attention of historians, so many of the images of women physicians that circulated in the United States during the same period have come to be examined by literary scholars and critics. This ongoing scholarly consideration of literary representations of American women as physicians has evolved along a path that corresponds to important phases in literary studies generally since the 1970s: the emergence of second‐wave feminist criticism, a return to historically oriented modes of critical analysis, and the growth of interdisciplinary approaches, among other influential developments. Many such approaches to early imaginative representations of American women doctors have been flawed, however, in their use either of documentary evidence or of analytical paradigms drawn from the history of medicine, the history of science, and related fields. Moreover, critical discussion continues to focus primarily on a small fraction of the number of literary images of women doctors that proliferated in the United States between 1860 and 1920 – further illustrating how far this area of inquiry has yet to develop and expand in order to do justice to such a pervasive, conspicuous phenomenon in American literary history.
Sensor of phospholipids in Streptomyces phospholipase D
Authors: Uesugi Yoshiko , Arima Jiro , Iwabuchi Masaki , Hatanaka Tadashi
Published: April 2007

Recently, we identified Ala426 and Lys438 of phospholipase D from Streptomyces septatus TH‐2 (TH‐2PLD) as important residues for activity, stability and selectivity in transphosphatidylation. These residues are located in a C‐terminal flexible loop separate from two catalytic HxKxxxxD motifs. To study the role of these residues in substrate recognition, we evaluated the affinities of inactive mutants, in which these residues were substituted with Phe and His, toward several phospholipids by SPR analysis. By substituting Ala426 and Lys438 with Phe and His, respectively, the inactive mutant showed a much stronger interaction with phosphatidylcholine and a weaker interaction with phosphatidylglycerol than the inactive TH‐2PLD mutant. We demonstrated that Ala426 and Lys438 of TH‐2PLD play a role in sensing the head group of phospholipids.
Enzymatic properties of the lactate dehydrogenase enzyme from Plasmodium falciparum
Authors: Shoemark Deborah K. , Cliff Matthew J. , Sessions Richard B. , Clarke Anthony R.
Published: April 2007

The lactate dehydrogenase enzyme from Plasmodium falciparum (PfLDH) is a target for antimalarial compounds owing to structural and functional differences from the human isozymes. The plasmodial enzyme possesses a five‐residue insertion in the substrate‐specificity loop and exhibits less marked substrate inhibition than its mammalian counterparts. Here we provide a comprehensive kinetic analysis of the enzyme by steady‐state and transient kinetic methods. The mechanism deduced by product inhibition studies proves that PfLDH shares a common mechanism with the human LDHs, that of an ordered sequential bireactant system with coenzyme binding first. Transient kinetic analysis reveals that the major rate‐limiting step is the closure of the substrate‐specificity loop prior to hydride transfer, in line with other LDHs. The five‐residue insertion in this loop markedly increases substrate specificity compared with the human muscle and heart isoforms.
Identification of substrates for transglutaminase in Physarum polycephalum, an acellular slime mold, upon cellular mechanical damage
Authors: Wada Fumitaka , Hasegawa Hiroki , Nakamura Akio , Sugimura Yoshiaki , Kawai Yoshiki , Sasaki Narie , Shibata Hideki , Maki Masatoshi , Hitomi Kiyotaka
Published: April 2007

Transglutaminases are Ca2+‐dependent enzymes that post‐translationally modify proteins by crosslinking or polyamination at specific polypeptide‐bound glutamine residues. Physarum polycephalum, an acellular slime mold, is the evolutionarily lowest organism expressing a transglutimase whose primary structure is similar to that of mammalian transglutimases. We observed transglutimase reaction products at injured sites in Physarum macroplasmodia upon mechanical damage. With use of a biotin‐labeled primary amine, three major proteins constituting possible transglutimase substrates were affinity‐purified from the damaged slime mold. The purified proteins were Physarum actin, a 40 kDa Ca2+‐binding protein with four EF‐hand motifs (CBP40), and a novel 33 kDa protein highly homologous to the eukaryotic adenine nucleotide translocator, which is expressed in mitochondria. Immunochemical analysis of extracts from the damaged macroplasmodia indicated that CBP40 is partly dimerized, whereas the other proteins migrated as monomers on SDS/PAGE. Of the three proteins, CBP40 accumulated most significantly around injured areas, as observed by immunofluoresence. These results suggested that transglutimase reactions function in the response to mechanical injury.
Subunit S5a of the 26S proteasome is regulated by antiapoptotic signals
Authors: Gus Yael , Karni Rotem , Levitzki Alexander
Published: April 2007

We performed a functional genetic screen to find novel antiapoptotic genes that are under the regulation of the oncoprotein c‐Src. Several clones were identified, including subunit S5a of the 26S proteasome. We found that S5a rescued Saos‐2 cells from apoptosis induced by Src inhibitor 4‐amino‐5‐(4‐methylphenyl)‐7‐(t‐butyl)pyrazolo[3,4‐d]pyrimidine (PP1). S5a mRNA and protein levels were downregulated as a result of Src inhibition, either by siRNA or PP1. In cell lines that possess high activity of Src S5a levels were elevated. Cloning of the S5a promoter region showed that S5a transcription responds to several stimuli. Analysis of the promoter sequence revealed a binding site for Tcf/Lef‐1 transcription factor. Indeed, β‐catenin significantly induced transcription from the S5a promoter, whereas EMSA studies showed that Lef‐1 binds the S5a promoter‐binding site. Furthermore, we also found that PP1 and LY294002, but not PD98059 inhibit the S5a promoter activity. These results suggest that S5a is regulated during apoptosis at the transcriptional level and that S5a upregulation by antiapoptotic signals can contribute to cell survival.
A Family Systems‐Based Model of Organizational Intervention
Authors: Shumway Sterling T. , Kimball Thomas G. , Korinek Alan W. , Arredondo Rudy
Published: April 2007

Employee assistance professionals are expected to be proficient at intervening in organizations and creating meaningful behavioral change in interpersonal functioning. Because of their training in family systems theories and concepts, marriage and family therapists (MFTs) are well suited to serve organizations as “systems consultants.” Unfortunately, the authors were unable to identify any family systems‐based models for organizational intervention that have been empirically tested and supported. In this article, the authors present a family systems‐based model of intervention that they developed while working in an employee assistance program (EAP). They also present research that was used to refine the model and to provide initial support for its effectiveness.
Attachment‐Based Family Therapy: Adherence and Differentiation
Authors: Diamond Gary M. , Diamond Guy S. , Hogue Aaron
Published: April 2007

This study examined the fidelity of attachment‐based family therapy (ABFT) for depressed adolescents. Trained observers used the therapist behavior rating scale (3rd version) to code therapist behaviors in 45 sessions of ABFT and 45 sessions each from two empirically based treatments for adolescent substance abusers: multidimensional family therapy (MDFT) and cognitive‐behavioral therapy (CBT). Results indicate that ABFT therapists employed essential ABFT interventions, such as focusing on vulnerable affect, highlighting attachment‐related themes, and promoting adolescent–parent reattachment through in‐session enactments. In accordance with the sequential nature of the treatment, these interventions were used more extensively during the early stage of treatment, when there is a greater focus on reattachment. ABFT was perfectly discriminable from CBT, with ABFT therapists using more restructuring and reattachment interventions and CBT therapists using more signature CBT interventions, such as cognitive monitoring and homework. ABFT was also discriminable from MDFT, with ABFT therapists placing a greater emphasis on reattachment. These results suggest that ABFT is a viable and differentiated treatment. Together with prior findings supporting its efficacy, ABFT should be considered a promising new approach for working with depressed adolescents and their families.
Relationship Violence Among Couples Seeking Therapy: Common Couple Violence or Battering?
Authors: Simpson Lorelei E. , Doss Brian D. , Wheeler Jennifer , Christensen Andrew
Published: April 2007

Relationship violence is highly prevalent among couples seeking therapy (Ehrensaft & Vivian, 1996; Jouriles & O’Leary, 1985), yet few couple therapists regularly assess for violence (Dimidjian, Berns, & Jacobson, 1999), and there is limited research on the type of violence most characteristic of couples in this population. The current study uses latent class analysis to examine types of violence in a sample of 273 therapy‐seeking couples. The results support a three‐class typology, with the groups labeled no violence, low‐level violence, and moderate‐to‐severe violence. Comparisons between the classes support hypothesized differences between groups in degree of marital satisfaction and difficulties in communication, providing further validation of the typology among couples seeking treatment. Clinical and research implications are discussed.
Ultrasonic Cavitation-Based Nanomanufacturing of Bulk Aluminum Matrix Nanocomposites
Authors: Yang Yong , Li Xiaochun
Published: April 2007

Lightweight metal matrix nanocomposites (MMNCs) (metal matrix with nanosized ceramic particles) can be of significance for automobile, aerospace, and numerous other applications. It would be advantageous to develop effective nanomanufacturing methods for fabrication of bulk components of aluminum-based MMNCs through solidification processing. However, it is extremely difficult to disperse nanosized ceramic particles uniformly in molten aluminum. In this paper, a high power ultrasonic probe is used to disperse nanosized SiC particles into molten aluminum alloy A356. Experimental results show that the ultrasonic cavitation based dispersion of nanoparticles in molten aluminum alloy is effective. The uniform nanoparticle dispersion in the Al alloy matrix resulted in significantly improved mechanical properties. To enhance the nanomanufacturing efficiency, various nanoparticle feeding techniques were explored and experimental results are presented.
Numerical Analysis of Wall Slip Effects on Flow of Newtonian and Non-Newtonian Fluids in Macro and Micro Contraction Channels
Authors: Sunarso Alfeus , Yamamoto Takehiro , Mori Noriyasu
Published: April 2007

We performed numerical simulation to investigate the effects of wall slip on flow behaviors of Newtonian and non-Newtonian fluids in macro and micro contraction channels. The results show that the wall slip introduces different vortex growth for the flow in micro channel as compared to that in macro channel, which are qualitatively in agreement with experimental results. The effects of slip on bulk flow behaviors depend on rheological property of the fluid. For Newtonian fluid, the wall slip always reduces the vortex length, while for non-Newtonian fluid, the strength of the slip determines whether the vortex length is reduced or increased. Analyses on the velocity and stress fields confirm the channel size dependent phenomena, such as the reduction of wall shear stress with the decrease in channel size. With the increase in average shear rate, the Newtonian fluid shows the reduction of wall shear stress that increases in the same trend with slip velocity-wall shear stress function, while for non-Newtonian fluid, the effect of the slip is suppressed by shear thinning effect and, therefore, the reduction of wall shear stress is less sensitive to the change in average shear rate and slip velocity-wall shear stress function.
Modeling of Surface Roughness and the Role of Debris in Micro-EDM
Authors: Krishna Kiran M. P. S. , Joshi Suhas S.
Published: April 2007

Surface roughness is one of the important quality characteristic of a micromachined component. This paper presents a model to predict surface roughness of micro-EDmachined surfaces. The model is based on the configuration of a single-spark cavity formed as a function of process parameters. Assuming the normal distribution of surface heights, the μ and σ(Rq) of the surface profile are evaluated after every spark. The model was further extended to capture the role of debris in micro-EDM in changing electric potential at the micropeaks on the cathode surfaces. The chemical kinetics approach was used to evaluate the change in plasma enthalpy and composition as a result of debris inclusion in the dielectric. The corresponding energy distribution between the electrodes was used to predict configuration of the single-spark cavity and the consequent surface roughness using the earlier surface roughness model. The modeling results were found to agree well with the micro-EDM validation experiments performed without and with the inclusion of artificial debris (iron particles) in the dielectric.
Numerical Investigation of Opposing Dual Sided Microscale Laser Shock Peening
Authors: Fan Yajun , Wang Youneng , Vukelic Sinisa , Yao Y. Lawrence
Published: April 2007

Laser shock peening (LSP) is an innovative process which imparts compressive residual stresses in the processed surface of metallic parts to significantly improve fatigue life and fatigue strength of this part. In opposing dual sided LSP, the workpiece can be simultaneously irradiated or irradiated with different time lags to create different surface residual stress patterns by virtue of the interaction between the opposing shock waves. In this work, a finite element model, in which the hydrodynamic behavior of the material and the deviatoric behavior including work hardening and strain rate effects were considered, was applied to predict residual stress distributions in the processed surface induced under various conditions of the opposing dual sided microscale laser shock peening. Thus the shock waves from each surface will interact in different ways through the thickness resulting in more complex residual stress profiles. Additionally, when treating a thin section, opposing dual sided peening is expected to avoid harmful effects such as spalling and fracture because the pressures on the opposite surfaces of the target balance one another and prohibit excessive deformation of the target. In order to better understand the wave–wave interactions under different conditions, the residual stress profiles corresponding to various workpiece thicknesses and various irradiation times were evaluated.
Effects of Ploughing Forces and Friction Coefficient in Microscale Machining
Authors: Venkatachalam Siva , Liang Steven Y.
Published: April 2007

This paper discusses the effects of ploughing and friction in microscale machining. The friction coefficient has previously been shown to be sensitive to the geometry of the abrasive particle and the depth of indentation. From a micromachining standpoint, the friction coefficient is modeled to be a function of the tool edge radius and the undeformed chip thickness, wherein the tool edge is modeled as a sliding cylinder on a flat workpiece. The contributions of ploughing force, which assumes significance in microscale machining, are better modeled using an integration approach over the edge of the tool. Two force models for the estimation of ploughing forces are compared, wherein one model uses a slip-line field analysis and the other uses a method of force balance on the deformation boundary. Basic microcutting (shaping) experimental data are presented and compared to the prediction results. The results show that a nonuniform friction coefficient improves the predictability of the force model.
Study of the Mechanism of Groove Wear of the Diamond Tool in Nanoscale Ductile Mode Cutting of Monocrystalline Silicon
Authors: Cai M. B. , Li X. P. , Rahman M.
Published: April 2007

In nanoscale ductile mode cutting of the monocrystalline silicon wafer, micro-, or nanogrooves on the diamond cutting tool flank face are often observed, which is beyond the understanding based on conventional cutting processes because the silicon workpiece material is monocrystalline and the hardness is lower than that of the diamond cutting tool at room temperature. In this study, the mechanism of the groove wear in nanoscale ductile mode cutting of monocrystalline silicon by diamond is investigated by molecular dynamics simulation of the cutting process. The results show that the temperature rise in the chip formation zone could soften the material at the flank face of the diamond cutting tool. Also, the high hydrostatic pressure in the chip formation region could result in the workpiece material phase transformation from monocrystalline to amorphous, in which the material interatomic bond length varies, yielding atom groups of much shorter bond lengths. Such atom groups could be many times harder than that of the original monocrystalline silicon and could act as “dynamic hard particles” in the material. Having the dynamic hard particles ploughing on the softened flank face of the diamond tool, the micro-/nanogrooves could be formed, yielding the micro-/nanogroove wear as observed.
Impaired adaptation to repeated restraint and decreased response to cold in urocortin 1 knockout mice
Authors: Zalutskaya Alena A. , Arai Maya , Bounoutas George S. , Abou-Samra Abdul B.
Published: April 2007

Urocortin 1 (UCN1) is a corticotropin-releasing factor (CRF)-like peptide whose role in stress is not well characterized. To study the physiological role of UCN1 in the response of the hypothalamic-pituitary-adrenal (HPA) axis to stress, we generated UCN1-knockout (KO) mice and examined their adaptation to repeated restraint and to cold environment. Wild-type (WT) and UCN1-KO animals were restrained hourly for 15 min from 9 AM to 2 PM, and blood samples were obtained for corticosterone measurement. WT animals adapted to repeated restraint with a decreased corticosterone response; the restraint-stimulated corticosterone levels fell from 215 ± 31 ng/ml in naïve animals to 142 ± 50 ng/ml in mice subjected to repeated restraint ( P < 0.01) and from 552 ± 98 to 314 ± 58 ng/ml ( P < 0.001) in males and females, respectively. Male UCN1-KO mice did not show any adaptation to repeated restraint; instead, restraint-stimulated corticosterone levels were increased from 274 ± 80 ng/ml in naïve animals to 480 ± 75 ng/ml in mice subjected to repeated restraint ( P < 0.001). Female UCN1-KO mice showed only a partial adaptation to repeated restraint, with a decrease in the restraint-stimulated corticosterone response from 631 ± 102 ng/ml in naïve animals to 467 ± 78 ng/ml in mice subjected to repeated restraint ( P < 0.01). In addition, UCN1-KO mice showed no corticosterone response to 2-h cold environment. These data demonstrate an important role for UCN1 in the HPA axis adaptation to repeated restraint and in the corticosterone response to a cold environment.
Insulin granule trafficking in β-cells: mathematical model of glucose-induced insulin secretion
Authors: Bertuzzi Alessandro , Salinari Serenella , Mingrone Geltrude
Published: April 2007

A mathematical model that represents the dynamics of intracellular insulin granules in β-cells is proposed. Granule translocation and exocytosis are controlled by signals assumed to be essentially related to ATP-to-ADP ratio and cytosolic Ca2+ concentration. The model provides an interpretation of the roles of the triggering and amplifying pathways of glucose-stimulated insulin secretion. Values of most of the model parameters were inferred from available experimental data. The numerical simulations represent a variety of experimental conditions, such as the stimulation by high K+ and by different time courses of extracellular glucose, and the predicted responses agree with published experimental data. Model capacity to represent data measured in a hyperglycemic clamp was also tested. Model parameter changes that may reflect alterations of β-cell function present in type 2 diabetes are investigated, and the action of pharmacological agents that bind to sulfonylurea receptors is simulated.
Expression changes in mouse brains following nicotine-induced seizures: the modulation of transcription factor networks
Authors: Kedmi Merav , Orr-Urtreger Avi
Published: April 2007

Nicotine, acting through the neuronal nicotinic acetylcholine receptors (nAChRs), can induce seizures in mice. We aimed to study brain transcriptional response to seizure and to identify genes whose expression is altered after nicotine-induced seizures. Whole brains of untreated mice were compared with brains 1 h after seizure activity, using Affymetrix U74Av2 microarrays. Experimental groups included wild-type mice and both nicotine-induced seizure-sensitive and -resistant nAChR mutant mice. Each genotype group received different nicotine doses to generate seizures. This approach allowed the identification of significantly changed genes whose expression was dependent on seizure activity, nicotine administration, or both but not on the type of nAChR subunit mutation or the amount of nicotine injected. Significant expression changes were detected in 62 genes ( P < 0.05, false discovery rate correction). Among them, gene ontology functional annotation analysis determined that the most significantly overrepresented categories were of genes encoding MAP kinase phosphatases, regulators of transcription and nucleosome assembly proteins. In silico bioinformatic analysis of the promoter regions of the 62 changed genes detected significant enrichments of 16 transcription regulatory elements (TREs), creating a network of transcriptional regulatory responses to seizures. The TREs for activating transcription factor and serum response factor were most significantly enriched, supporting their association with seizure activity. Our data suggest that nicotine-induced seizure in mice is a useful model to study seizure activity and its global brain transcriptional response. The differentially expressed genes detected here can help us to understand the molecular mechanisms underlying seizures in animal models and may also serve as candidate genes to study epilepsy in humans.
LOXL1 and LOXL4 Are Epigenetically Silenced and Can Inhibit Ras/Extracellular Signal-Regulated Kinase Signaling Pathway in Human Bladder Cancer
Authors: Wu Guojun , Guo Zhongmin , Chang Xiaofei , Kim Myoung Sook , Nagpal Jatin K. , Liu Junwei , Maki Joni M. , Kivirikko Kari I. , Ethier Stephen P. , Trink Barry , Sidransky David
Published: April 2007

Promoter hypermethylation is one of the common mechanisms leading to gene silencing in various human cancers. Using a combination of pharmacologic unmasking and microarray techniques, we identified 59 candidate hypermethylated genes, including LOXL1, a lysyl oxidase-like gene, in human bladder cancer cells. We further showed that LOXL1 and LOXL4 are commonly silenced genes in human bladder cancer cells, and this silence is predominantly related to promoter methylation. We also found LOXL1 and LOXL4 gene methylation and loss of expression in primary bladder tumors. In addition, somatic mutations were identified in LOXL4, but not in LOXL1 in bladder cancer. Moreover, reintroduction of LOXL1 and LOXL4 genes into human bladder cancer cells leads to a decrease of colony formation ability. Further studies indicated that the overexpression of LOXL1 and LOXL4 could antagonize Ras in activating the extracellular signal-regulated kinase (ERK) signaling pathway. Thus, our current study suggests for the first time that lysyl oxidase-like genes can act as tumor suppressor genes and exert their functions through the inhibition of the Ras/ERK signaling pathway in human bladder cancer. [Cancer Res 2007;67(9):4123–9]
The SIL Gene Is Essential for Mitotic Entry and Survival of Cancer Cells
Authors: Erez Ayelet , Castiel Asher , Trakhtenbrot Luba , Perelman Marina , Rosenthal Esther , Goldstein Itamar , Stettner Noa , Harmelin Alon , Eldar-Finkelman Hagit , Campaner Stefano , Kirsch Ilan , Izraeli Shai
Published: April 2007

Although mitosis is a general physiologic process, cancer cells are unusually sensitive to mitotic inhibitors. Therefore, there is an interest in the identification of novel mitotic inhibitors. Here, we report the novel discovery of the SIL gene as a regulator of mitotic entry and cell survival. The SIL gene was cloned from leukemia-associated chromosomal translocation. It encodes a cytosolic protein with an unknown function and no homology to known proteins. Previously, we observed an increased expression of SIL in multiple cancers that correlated with the expression of mitotic spindle checkpoint genes and with increased metastatic potential. Here, we show that SIL is important for the transition from the G2 to the M phases of the cell cycle. Inducible knockdown of SIL in cancer cells in vitro delayed entrance into mitosis, decreased activation of the CDK1 (CDC2)-cyclin B complex, and induced apoptosis in a p53-independent manner. SIL is also essential for the growth of tumor explants in mice. Thus, SIL is required for mitotic entry and cancer cell survival. Because increased expression of SIL has been noted in multiple types of cancers and correlates with metastatic spread, it may be a suitable target for novel anticancer therapy. [Cancer Res 2007;67(9):4022–7]
Treatment of Refractory Pemphigus with the Anti-CD20 Monoclonal Antibody (Rituximab)
Authors: Marzano Angelo V. , Fanoni Daniele , Venegoni Luigia , Berti Emilio , Caputo Ruggero
Published: April 2007

Background: Pemphigus is a severe blistering disorder caused by autoantibodies to desmogleins 1 and 3. Because some patients with pemphigus never enter into remission, new immunosuppressants are warranted. Rituximab is a chimeric monoclonal antibody binding to the CD20 antigen on B cells, which proved to be effective in recalcitrant pemphigus. Objectives: To evaluate the efficacy and safety of rituximab in refractory pemphigus and to investigate its effects on the autoantibody profile. Patients and Methods: Six patients with recalcitrant pemphigus were treated. Rituximab was administered intravenously at a dosage of 375 mg/m2 body surface once weekly for 4 weeks. Results: Three pemphigus foliaceus patients and 1 with mucocutaneous pemphigus vulgaris (PV) showed complete response over a follow-up period of up to 18 months. In one oral PV, control of the disease was achieved using pulse therapy with cyclophosphamide following rituximab withdrawal. In one PV with vegetating features, good improvement was obtained after 6 rituximab infusions. All patients tolerated the treatment well. Anti-desmoglein autoantibodies significantly decreased only in pemphigus foliaceus. Conclusions: This study highlights that rituximab is a valuable drug for refractory pemphigus, although the response of mucous membranes and cutaneous folds may be delayed.
Increased Number of Cytotoxic CD3+CD28– γδ T Cells in Peripheral Blood of Patients with Cutaneous Malignant Melanoma
Authors: Campillo José A. , Martínez-Escribano Jorge A. , Minguela Alfredo , López-Álvarez Rocío , Marín Luis A. , García-Alonso Ana M. , Bensussan Armand , Álvarez-López María Rocío
Published: April 2007

Background: A rise of CD3+TCRγδ+CD28– T cells has previously been observed after anin vitro long-lasting activation or even during viral infection. Objective: The aim of this study was to investigate the expression of CD28 on lymphocytes bearing CD3/TCRγδ receptors in cancer, i.e. cutaneous melanoma. Methods: TCRγδ lymphocytes were analysed in 41 Caucasian melanoma patients and 39 healthy individuals by flow cytometry. Patients were stratified according to the American Joint Committee on Cancer (AJCC) clinical stage. Results: The number of circulating CD3+TCRγδ+ T cells was significantly increased in both AJCC stages I–II and AJCC stage III patients compared with healthy individuals. This increase was mediated by an accumulation of the CD3+TCRγδ+CD28– T-cell subset, which expressed a high amount of perforin both in normal individuals and melanoma patients. Conclusion: This work shows, for the first time, a rise of the cytotoxic CD3+TCRγδ+CD28– T-cell population in melanoma patients, which may be important in anticancer surveillance.
Lack of Association between Exposure to Topical Calcineurin Inhibitors and Skin Cancer in Adults
Authors: Margolis David J. , Hoffstad Ole , Bilker Warren
Published: April 2007

Background: Two topical calcineurin inhibitors (TCI) are available for the treatment of atopic dermatitis and there has been concern that their use could be associated with an increased risk of nonmelanoma skin cancer (NMSC). Objective: To determine if TCI exposure is associated with an increased risk of NMSC in adults. Methods: A case-control study using a questionnaire mailed to 5,000 adults with dermatitis. Results: We received responses from 70.7% of those surveyed by mail. Overall, 25.7% reported exposure to TCI. TCI exposure was 14.4% for the cases and 30.7% for the controls. Our primary analysis was a comparison between those with NMSC and those without. The unadjusted odds ratio was 0.38 (0.31–0.47) and the adjusted (age, gender, previous NMSC, history of atopic dermatitis) was 0.54 (0.41–0.69). The odds ratio of association for NMSC decreased as the number of tubes used and the potency of the agent increased. Conclusion: This early study shows that TCI use is not associated with an increased risk of NMSC in adults.
Serum Levels of the Th1 Promoter IL-12 and the Th2 Chemokine TARC Are Elevated in Erythema Multiforme and Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis and Correlate with Soluble Fas Ligand Expression
Authors: Quaglino Pietro , Caproni Marzia , Antiga Emiliano , Del Bianco Elena , Osella-Abate Simona , Savoia Paola , Frezzolini Alessandra , Schena Donatella , Marzano Angelo , Volpi Walter , De Simone Clara , Parodi Aurora , Fabbri Paolo , Bernengo Maria Grazia
Published: April 2007

Background: No data exist as to Th2 chemokines in erythema multiforme (EM) and Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN). Objective: To evaluate thymus- and activation-regulated chemokine (TARC), macrophage-derived chemokine (MDC) and regulated upon activation, normal T-lymphocyte-expressed and secreted chemokine (RANTES) expression in EM and SJS/TEN and to correlate with the serum levels of the Th1 promoter interleukin (IL)-12 and soluble Fas ligand (sFasL). Materials and Methods: IL-12, sFasL, TARC, MDC and RANTES expression were analyzed by ELISA techniques in 31 untreated EM (n = 24) or SJS/TEN (n = 7) patients and in 28 healthy donors (HD). Results: EM and SJS/TEN exhibited significantly higher levels of TARC, IL-12 and sFasL with respect to HD. TARC upregulation paralleled both the IL-12 (p = 0.0225) and sFasL increase (p = 0.0194). Conclusions: Our results support a role of TARC in the pathophysiology of EM/SJS/TEN and confirm the coexistence of a Th2 response in addition to the predominant Th1 profile.
Dialyzable Uremic Solutes Contribute to Enhanced Oxidation of Serum Albumin in Regular Hemodialysis Patients
Authors: Terawaki Hiroyuki , Nakayama Keisuke , Matsuyama Yukie , Nakayama Masaaki , Sato Toshinobu , Hosoya Tatsuo , Era Seiichi , Ito Sadayoshi
Published: April 2007

Background: Oxidative stress (OS) is reportedly enhanced in patients receiving regular hemodialysis (HD). However, the in vivo redox state of HD patients, particularly after HD sessions, remains unclear. This study aimed to clarify the influence of HD on OS using the albumin redox state as a marker. Method: Blood samples of 8 regular HD patients were obtained during the course of study. The redox state of albumin was determined using high-performance liquid chromatography. Results: The mean fraction of reversibly oxidized albumin [f(HNA-1)] declined significantly over the course of the session and reached a minimum 4 h after the session had ended (pre-HD, 36.16 ± 7.50%; 4 h after HD, 25.71 ± 6.41%), then gradually rose to predialytic levels. The proportion of irreversibly oxidized albumin did not change significantly over time. Positive correlations were demonstrated between f(HNA-1) and uremic small solutes in each case. Conclusion: Accumulation of dialyzable uremic solutes may contribute to OS in HD patients.
Endothelin-1 Induces NF-κB via Two Independent Pathways in Human Renal Tubular Epithelial Cells
Authors: Gerstung Melanie , Roth Tanja , Dienes Hans-Peter , Licht Christoph , Fries Jochen W.U.
Published: April 2007

Background: Endothelin-1 (ET-1) is a major transcriptional activator of renal proximal tubule cells acting in an autocrine and paracrine manner. In animal studies, ET-1 has been implicated in progressive renal interstitial fibrosis by promoting gene expression, possibly via the inflammatory NF-ĸB signal pathway. While ET-1-dependent mechanisms of signal transduction have been studied mainly in tumor cell lines, we analyzed the mechanism of ET-1-induced, NF-ĸB-mediated target gene activation in proximal tubule cells. Methods: Human renal proximal tubule cells were stimulated with ET-1 and gene expression analyzed by protein microarray, Western blot, non-radioactive electromobility shift assay, and quantitative real-time polymerase chain reaction. Results: Activation of NF-ĸB occurs only via an ET-1-specific type A receptor (not type B as in animals). Induction can be blocked by bosentan, and endothelin-A but not endothelin-B receptor-specific antagonists. Protein microarray screening shows activation of two independent cascades (via the endothelin-A receptor, or via diacylglycerol) leading to NF-ĸB induction. The independent induction is also reflected by target gene expression such as the vascular cell adhesion molecule-1, interleukin-6, and fractalkine at different time points. Conclusion: Thus prohibiting ET-1-mediated gene transcription necessitates blocking of NF-ĸB and diacylglycerol signal transduction in proximal tubule cells.
The Effect of Civil War on Education, 1980—97
Authors: Lai Brian , Thyne Clayton
Published: April 2007

This study examines the negative effects of civil wars and the post-civil war environment on educational expenditures and enrollment. Two causal mechanisms are considered. First, civil wars are likely to destroy a state's system of education through the loss of infrastructure and personnel. Second, a less deleterious cause may be the drawing away of funds for increased military expenditures to fight the civil war. Using UNESCO education data, the authors examine the percent change in educational expenditures and primary, secondary, and tertiary enrollment for all states from 1980 through 1997. The authors use a measure of when a state is in a civil war, a dynamic post-civil war measure, an interaction with military spending, and relevant control variables. The results indicate strong support for the notion that civil war is devastating for a system of education, as both expenditures and enrollment decline during periods of civil war. No support was found for the reallocation of education funds towards military spending during a civil war. These results highlight the importance of addressing the social costs of a civil war. Civil wars do not simply impose social costs because of increased funding to the military; rather, they severely disrupt a state's ability to provide even basic social services.
Governments Against States
Authors: Englehart Neil A.
Published: April 2007

Although state failure has assumed considerable importance in the post-cold-war world, attempts to predict its occurrence statistically have not been very successful. Such attempts rely on off-the-shelf data collected for other purposes. To predict state failure, we need data more specific to the problem. A better body of theory is required to identify causal patterns, and case studies are a promising way to proceed. Case studies of paradigmatic state failures in Somalia and Afghanistan suggest a pattern: rulers attack the state apparatus in order to prevent opposition by the bureaucracy and military, precipitating the collapse of the state.
The Three Sources of Legitimacy for European Fiscal Policy
Authors: Collignon Stefan
Published: April 2007

Fiscal policy has remained under the authority of national governments in “Euroland,” while monetary policy is unified in the hands of the European Central Bank. This arrangement does not produce optimal results. This article looks at the normative foundations of fiscal policy in the European Union, by mapping the allocative function, stabilization, and redistribution policies onto three models of legitimacy: the problem-solving European Union, the communitarian model, and the European Republic.
Informational Ideas
Authors: Arnoldi Jakob
Published: April 2007

Based on an empirical study of the British think tank Demos, the article deliberates on the nature of current political ideas. The key argument is that such a deliberation must take into account not only ideas of production but also ideas of mediation. The article argues that the ability to disseminate, brand, and market political ideas in the public sphere through the mass media is a crucial part of the activities of modern idea producers such as think tanks. Ideas are normally conceptualized as statements. As an analytical tool, the article makes a distinction between the two components of a statement. The two components are utterance (or impartation) and proposition (or semantic unit more generally). By so doing, it is possible to focus on (1) the necessity for think tanks to be an `impartational node' in communicative networks and (2) the importance of attributing certain meanings and values to the political ideas (to brand ideas). From this theoretical outset, the article then describes the logic or nature of the mediation, marketing and branding of political ideas.
Adult Learning in New Social Movements: Environmental Protest and the Struggle for the Clayoquot Sound Rainforest
Authors: Walter Pierre
Published: April 2007

During the summer of 1993, some 10,000 people, young and old, joined logging road blockades to protest the clear-cutting of old-growth temperate rainforest in Clayoquot Sound, British Columbia, Canada. By the end of the summer, more than 900 protestors had been arrested for acts of civil disobedience in refusing to leave the road. In subsequent mass trials, many were then convicted of criminal contempt of court and sentenced to jail terms and steep fines for their activism. Led primarily by women and espousing feminist principles of nonviolence and consensus decision making, the 1993 protests and Clayoquot Peace Camp became the focal point of an environmental movement that eventually spread far beyond the Sound. Framed by the field of adult learning in new social movements and environmental adult education, this article examines the history of Clayoquot Sound protest, its philosophy and practices of learning, education and activism, and its outcomes and significance to adult education.