bluuebunny/crossref_metadata_2025 huggingface dataset:
Engaging Suffering: Towards A Mindful Re‐Visioning of Family Therapy Practice
Authors: Gehart Diane R. , McCollum Eric E.
Published: April 2007

The myth of problem‐free living is easily identifiable in Western culture through its childhood fairy tales and modern love stories. Even if inadvertently, the field of mental health perpetuates this myth with the very concept of “mental health,” which implies a state without suffering. Using mindfulness, Buddhists assume an alternative stance towards suffering: rather than eliminate it, they compassionately engage it. This article explores the potentials of mindfulness as an alternative approach to suffering within the context of marriage and family therapy. Family therapists can integrate mindfulness principles into their work to help clients shift how they relate to the unique forms of suffering that one encounters in intimate relationships, such as abuse, divorce, rejection, and loss.
Therapists’ Prototypical Assessment of Domestic Violence Situations
Authors: Blasko Kelly A. , Winek Jon L. , Bieschke Kathleen J.
Published: April 2007

Prototypical perceptions by therapists have the potential to influence the therapeutic process of assessment. The purpose of this study is to begin to develop an understanding of how prototypes might affect marriage and family therapists’ assessments of domestic violence situations. Participants evaluated one of three domestic violence scenarios that were identical in dynamics but different in terms of sexual orientation of the couple (i.e., heterosexual, gay, or lesbian). The most significant finding was that initial assessments of victim and perpetrator identification and power attribution differed depending on the sexual orientation of the couple. The “man as perpetrator, woman as victim” prototypical paradigm for heterosexual domestic violence emerged. In the same‐sex scenarios, often “both” partners were perceived to be indicated both as victim and perpetrator.
On the Mechanisms Affecting Fluidic Vectoring Using Suction
Authors: Gillgrist R. D. , Forliti D. J. , Strykowski P. J.
Published: April 2007

Suction was applied asymmetrically to the exhaust of a rectangular subsonic jet creating a pressure field capable of vectoring the primary flow at angles up to 15deg. The suction simultaneously creates low pressures near the jet exhaust and conditions capable of drawing a secondary flow along the jet shear layer in the direction opposite to the primary jet. This countercurrent shear layer is affected both by the magnitude of the suction source as well as the proximity of an adjacent surface onto which the pressure forces act to achieve vectoring. This confined countercurrent flow gives rise to elevated turbulence levels in the jet shear layer as well as considerable increases in the gradients of the turbulent stresses. The turbulent stresses are responsible for producing a pressure field conducive for vectoring the jet at considerably reduced levels of secondary mass flow than would be possible in their absence.
Thermal and Flow Fields Modeling of Fast Spark Discharges in Air
Authors: Ekici O. , Ezekoye O. A. , Hall M. J. , Matthews R. D.
Published: April 2007

In this study, a two-dimensional axisymmetric computational model of spark discharge in air is presented to provide a better understanding of the dynamics of the process. Better understanding of the modeling issues in spark discharge processes is an important issue for the automotive spark plug community. In this work we investigate the evolution of the shock front, temperature, pressure, density, geometry, and flow history of a plasma kernel using various assumptions that are typically used in spark discharge simulations. A continuum, inviscid, heat conducting, single fluid description of the flow is considered with radiative losses. Assuming local thermal equilibrium, the energy input due to resistive heating is determined using a specified current profile and temperature-dependent gas electrical conductivity in the gap. The spark discharge model focuses on the early time flow physics, the relative importance of conduction and radiation losses, the influence of thermodynamic model choice and ambient pressure effects.
On the Stability of Two Superposed Viscous-Viscoelastic (Walters B′) Fluids
Authors: Kumar Pardeep , Lal Roshan
Published: April 2007

The Rayleigh-Taylor instability of a Newtonian viscous fluid overlying Walters B′ viscoelastic fluid is considered. For the stable configuration, the system is found to be stable or unstable under certain conditions. However, the system is found to be unstable for the potentially unstable configuration. Further it is found numerically that kinematic viscosity has a destabilizing effect, whereas kinematic viscoelasticity has a stabilizing effect on the system.
An Experimental Investigation on Semi-Solid Forming of Micro/Meso-Scale Features
Authors: Kim Gap-Yong , Ni Jun , Mayor Rhett , Kim Heesool
Published: April 2007

The potentials of semi-solid forming technology have generated much interest regarding its application in micromanufacturing. This study investigates the feasibility of using semi-solid forming technology to produce parts with micro/meso features. An experimental setup has been developed to study the effects of die/punch temperature, initial solid fraction, punch speed, and workpiece shape on the semi-solid forming process. A part has been produced for a microreactor application and has been analyzed with an optical measurement system for feature formation. The results indicated complex interaction among the process parameters and the material flow, which affected the final pin formation. The punch temperature and velocity had a significant effect on the overall die filling. The initial workpiece shape and solidification of the semi-solid material during forming influenced the micro/meso-feature formation sequence, affecting the final pin formation. Furthermore, grain deformation and distribution of the formed parts were investigated. The grains became larger due to induction heating and the forming process. Severely distorted grains were observed at the corner regions of the pins and the punch-workpiece interface.
Modeling of the Semi-Solid Material Behavior and Analysis of Micro-/Mesoscale Feature Forming
Authors: Kim Gap-Yong , Koç Muammer , Mayor Rhet , Ni Jun
Published: April 2007

One of the major challenges in simulation of semi-solid forming is characterizing the complex behavior of a material that consists of both solid and liquid phases. In this study, a material model for an A356 alloy in a semi-solid state has been developed for high solid fractions (>0.6) and implemented into a finite element simulation tool to investigate the micro-/mesoscale feature formation during the forming process. Compared to previous stress models, which are limited to expressing the stress dependency on only the strain rate and the temperature (or the solid fraction), the proposed stress model adds the capability of describing the semi-solid material behavior in terms of strain and structural evolution. The proposed stress model was able to explain the strain-softening behavior of the semi-solid material. Furthermore, a simulation model that includes the yield function, the flow rule, and the stress model has been developed and utilized to investigate the effects of various process parameters, including analysis type (isothermal vs nonisothermal), punch velocity, initial solid fraction, and workpiece shape (“flat” versus “tall”) on the micro-/mesofeature formation process.
Toxicity of ligand-dependent Cre recombinases and generation of a conditional Cre deleter mouse allowing mosaic recombination in peripheral tissues
Authors: Hameyer Dorothe , Loonstra Ate , Eshkind Leonid , Schmitt Steffen , Antunes Cecilia , Groen Annemiek , Bindels Eric , Jonkers Jos , Krimpenfort Paul , Meuwissen Ralph , Rijswijk Loes , Bex Axel , Berns Anton , Bockamp Ernesto
Published: April 2007

Ligand-activated Cre recombinases are widely used for studying gene function in vitro and in conditional mouse models. To compare ligand-dependent Cre recombinases, different Cre estrogen receptor fusions were introduced into the ROSA26 locus of embryonic stem (ES) cells and assayed for genotoxicity and recombination efficiency. Of the tested recombinases, the CreERT2 variant showed no toxicity and was highly responsive to ligand induction. To constitutively express CreERT2 in mice and also to clarify whether the CreERT2 system displays background activity, we generated a knock-in mouse line harboring the CreERT2 coding region under the control of the ROSA26 locus. Analysis of this ROSA26-CreERT2 deleter mouse with different reporter strains revealed ubiquitous recombination in the embryo and partial recombination in peripheral and hematopoietic tissues but no effective CreERT2 expression in the brain. Furthermore, using flow cytometry, we found low-level background recombination in noninduced bitransgenic ROSA26-CreERT2/EGFP reporter mice. To determine whether background activity poses a general problem for conducting conditional in vivo experiments with the ROSA26-CreERT2 deleter, we used a sensitive conditional skin cancer model. In this assay, cancer induction was completely restricted to induced bitransgenic CreERT2/K-RasV12 mice, whereas noninduced control animals did not show any sign of cancer, indicating the usefulness of the ROSA-CreERT2 system for regulating conditional gene expression in vivo. The ROSA26-CreERT2 deleter strain will be a convenient experimental tool for studying gene function under circumstances requiring partial induction of recombination in peripheral tissues and will be useful for uncovering previously unknown or unsuspected phenotypes.
Are Itch and Chronic Pain Associated in Adults? Results of a Large Population Survey in Norway
Authors: Dalgard Florence , Dawn Aerlyn G. , Yosipovitch Gil
Published: April 2007

Background: Few large-scale epidemiological studies have been performed on the prevalence of itch. Itch and pain are common and complex symptoms which contribute to the burden of disease. Although there is antagonistic interaction between itch and pain, there are also many similarities in their pathophysiology. Objective: To investigate possible associations between chronic itch and chronic pain in a large population. Methods: The design was cross-sectional. 18,770 adults completed a self-administered questionnaire addressing sociodemographic factors, psychosocial factors and self-reported health including chronic itch and chronic pain. Results: Individuals reporting pain and itch were more likely to be women (80 and 60%, respectively, compared to 55% in the total sample), had a lower income (49 and 37% compared to 32%), were more likely to be depressed (36 and 20% compared to 11%) and reported poorer well-being (74 and 34% compared to 25%). In an adjusted logistic regression, chronic pain was strongly associated with chronic itch (OR = 1.79, 95% CI = 1.43–2.24). Conclusion: This study demonstrates the association of chronic itch and chronic pain and points out the need of further studies that focus on both symptoms in dermatological diseases.
Hidradenitis Suppurativa and Zinc: A New Therapeutic Approach
Authors: Brocard Anabelle , Knol Anne-Chantal , Khammari Amir , Dréno Brigitte
Published: April 2007

Background: Hidradenitis suppurativa (Verneuil’s disease) is a chronic suppurative dermatosis involving apocrine glands with a severe impact on the quality of life, which is enhanced by the fact that the drugs usually prescribed are poorly effective. Objective: We discuss a new therapeutic approach based on zinc salts. Methods: We performed a pilot study on 22 patients, mainly from grade I or II in Hurley’s classification. All included patients had previously been prescribed a treatment (antibiotic, isotretinoin, surgery or anti-androgens), which was inefficient. They were then treated with 90 mg of zinc gluconate per day (15 mg zinc per Rubozinc® capsule). Results: We observed a clinical response in all patients, with 8 complete remissions (CR) and 14 partial remissions (PR). When CR was obtained, the treatment was progressively decreased (average of 3.5 capsules/day); 4/22 patients experienced side-effects, mainly gastro-intestinal. Conclusion: Zinc salts could provide a new therapeutic alternative for the treatment of hidradenitis suppurativa.
Characteristics and Pathomechanisms of Endogenously Aged Skin
Authors: Makrantonaki Evgenia , Zouboulis Christos C.
Published: April 2007

The skin, being in direct contact with several environmental factors (e.g. UV irradiation), does not only undergo endogenous aging, which has to do with the ‘biological clock’ of the skin cells per se, but also exogenous aging. While exogenous skin aging has been extensively studied, the pathomechanisms of endogenous skin aging remain far less clear. Endogenous skin aging reflects reduction processes, which are common in internal organs. These processes include cellular senescence and decreased proliferative capacity, decrease in cellular DNA repair capacity and chromosomal abnormalities, loss of telomeres, point mutations of extranuclear mtDNA, oxidative stress and gene mutations. As a consequence, aged skin in nonexposed areas shows typical characteristics including fine wrinkles, dryness, sallowness and loss of elasticity. Recent data have illustrated that lack of hormones occurring with age may also contribute to the aging phenotype. Improvement of epidermal skin moisture, elasticity and skin thickness, enhanced production of surface lipids, reduction of wrinkle depth, restoration of collagen fibers and increase of the collagen III/I ratio have been reported after hormone replacement therapy or local estrogen treatment in postmenopausal women. Furthermore, an in vitro model of endogenous skin aging consisting of human SZ95 sebocytes which were incubated under a hormone-substituted environment illustrated that hormones at age- and sex-specific levels were able to alter the development of cells by regulating their transcriptome. In conclusion, among other factors the hormone environment plays a distinct role in the generation of aged skin.
Sigma Receptor Type 1 Gene Variation in a Group of Polish Patients with Alzheimer’s Disease and Mild Cognitive Impairment
Authors: Maruszak Aleksandra , Safranow Krzysztof , Gacia Magdalena , Gabryelewicz Tomasz , Słowik Agnieszka , Styczyńska Maria , Pepłońska Beata , Golan Maciej P. , Żekanowski Cezary , Barcikowska Maria
Published: April 2007

The sigma-1 receptor (SIGMAR1) is a subtype of a nonopioid sigma receptor family and is implicated in numerous functions connected with Alzheimer’s disease (AD). Two common genetic variants were identified in SIGMAR1: GC–241 –240TT and Q2P (A61C). It was suggested that the TT-C haplotype is a protective factor for AD. We decided to investigate a putative link between the variants of SIGMAR1 and AD in a group of Polish patients with late-onset AD, in patients with mild cognitive impairment, and in a control group. We observed no significant differences for the SIGMAR1 allele, genotype, haplotype, and diplotype distributions between the studied groups. Multivariate logistic regression analysis showed no interaction between the APOE4 and SIGMAR1 polymorphisms. Further studies using data from different populations are required to elucidate the effect of SIGMAR1 polymorphisms on AD.
β1 Integrins Mediate Tubule Formation Induced by Supernatants Derived from KSHV-Infected Cells
Authors: Dyson Ossie F. , Bryan Benjaman A. , Lambert Phelps J. , Ford Patrick W. , Akula Shaw M.
Published: April 2007

Objective: Angiogenesis is defined as the formation of new blood vessels. In a recently concluded study, we identified Kaposi’s sarcoma-associated herpesvirus (KSHV)-infected cells derived from primary effusion lymphoma (PEL) to overexpress vascular endothelial growth factor (VEGF) that had the propensity to mediate tubule formation on a Matrigel, an indicator of angiogenesis. The objective of this study was to determine the receptor molecules that mediate the tubule formation induced by the supernatant derived from KSHV-infected PEL cells. Methods: The identity of receptor(s) that play a role in mediating tubule formation driven by PEL supernatant was determined by the classical in vitro angiogenesis assay conducted on a Matrigel. Results: RGD peptides, antibodies, and siRNA specific to β1 integrins significantly lowered the ability of the PEL supernatants to induce tubule formation by endothelial cells. β1 Integrins mediated tubule formation to comparable levels in endothelial cells that were incubated with supernatants derived from uninduced or TPA-induced PEL cells. Interestingly, the β1 integrins did not seem to have a major role in cellular attachment. Conclusion: We report for the first time a critical role for β1 integrins in angiogenesis supported by the supernatant from KSHV-infected PEL cells.
Prepare Cells to Repair the Heart: Mesenchymal Stem Cells for the Treatment of Heart Failure
Authors: Ohnishi Shunsuke , Nagaya Noritoshi
Published: April 2007

Heart failure is one of the most important cardiovascular diseases, with high mortality, and invasive treatment such as mechanical circulatory support and cardiac transplantation is sometimes required for severe heart failure. Therefore, the development of less invasive and more effective therapeutic strategies is desired. Cell therapy is attracting growing interest as a new approach for the treatment of heart failure. As a cell source, various kinds of stem/progenitor cells such as bone marrow cells, endothelial progenitor cells, mesenchymal stem cells (MSC) and cardiac stem cells have been investigated for their efficacy and safety. Especially, bone marrow-derived MSC possess multipotency and can be easily expanded in culture, and are thus an attractive therapeutic tool for heart failure. Recent studies have revealed the underlying mechanisms of MSC in cardiac repair: MSC not only differentiate into specific cell types such as cardiomyocytes and vascular endothelial cells, but also secrete a variety of paracrine angiogenic and cytoprotective factors. It has also been suggested that endogenous MSC as well as exogenously transplanted MSC migrate and participate in cardiac repair. Based on these findings, several clinical trials have just been started to evaluate the safety and efficacy of MSC for the treatment of heart failure.
Moderators of Priming Effects: A Theory and Preliminary Evidence from an Experiment on Swiss European Policy
Authors: Marquis Lionel
Published: April 2007

This article proposes an extended model of how “media priming effects” come about, distinguishing between several mediators and moderators of priming. The model is tested using data from an experiment on Swiss foreign policy in which undergraduate students were provided with different types of biased information about the relationships between Switzerland and the European Union. The empirical analysis suggests that cross-sectional and cross-temporal effects are facilitated by quite different moderators, and that very few variables moderate priming according to both perspectives. In that respect, political knowledge, the level of recall of the experimental message, and awareness of the persuasive intent of the message appear central to the priming mechanism.
Word and Image: Framing Philology
Authors: Fliethmann Axel
Published: April 2007

This text focuses from a philological perspective on media theories and their impact on traditional text-based disciplines. Therefore it looks at the problems that have emerged for Media Studies as well as for traditional studies in philology when reflecting on the concept of self-reference, since their subjects can seemingly no longer rely on the purity of the written word. If research work in the field of humanities is still mainly documented by texts, how does the advance of images as a challenging research subject affect the text that is referring to that subject? Speaking in media terms: how is the medium `text', which still remains text when it is concerned with the medium `image', affected by the `other' medium? This question deals with the problem of self-reference, hence the construction of disciplinary limitations in various academic fields. Beginning with this question, I try to find out how the difference between self-reference (text) and reference (image) has been and still is being organized in texts. How can we compare different types of theorizing images in texts? These abstract problems will be exemplified by situating the word—image bias in a wider historical context. The text concludes by developing some possibilities for future research within this area of visual culture and academic writing.
Cultural Competence of International Humanitarian Workers
Authors: Chang Wei-Wen
Published: April 2007

As global interaction and cultural diversity become prominent, cultural competence has received more attention. To understand nonprofit organizations' (NPO's) international workers' learning process in terms of cultural competence, this study used a cultural competence attainment model as a theoretical framework, enlisted 10 Taiwanese international humanitarian workers, and explored how their expatriate experiences of local service influenced their cultural competence. This study identified three levels of influence, namely, the peripheral, cognitive, and reflective levels. Based on these findings, this study suggests the practice of designing related developmental activities in accordance with the three levels and more future research focusing on the process of acquiring cultural competence.
The effect of tobacco consumption on blood cholinesterase levels among workers exposed to organophosphorus pesticides
Authors: Mishra Gauravi A
Published: April 2007

This is a cross-sectional study of workers in the pesticide industry, engaged in the formulation and packaging of organophosphorus compounds. A detailed history was taken of all study participants. Investigations carried out were the measurement of haemoglobin levels and estimation of whole blood cholinesterase levels.

The prevalence of tobacco consumption in the industry is 76.09%. The mean age of employees was 42.8 years and the mean duration of service was 16.6 years. The study concludes that tobacco consumption increases the risk of toxicity due to organophosphorus pesticides, as indicated by a decrease in the blood cholinesterase levels. In this study, the age of employees and duration of service in the pesticide industry played no role in increasing the risk of toxic effects when exposed to organophosphorus pesticides. Toxicology and Industrial Health 2006; 22: 399-403.
Classifying radiographic progression status in early rheumatoid arthritis patients using propensity scores to adjust for baseline differences
Authors: Park Grace S. , Weng Kee Wong  , Oh MyungShin , Khanna Dinesh , Gold Richard H. , Sharp John T. , Paulus Harold E.
Published: April 2007

Various methods are used to measure radiographic joint damage in patients with rheumatoid arthritis (RA), but determining proportions of responsive patients is difficult. A key problem in observational studies when assessing damage outcomes is incorporating time to treatment initialization and adjusting for observed baseline differences. We examined five different definitions to select an appropriate index to classify radiographic damage in RA patients as progressive or nonprogressive. In addition, we compared different times from symptom onset to treatment and their effects on patient radiographic categorization. Propensity scores to adjust for baseline differences, including time since symptom onset, were used to match those treated early with those treated later using the stratification, radius, nearest neighbor and kernel methods. The mean effect of treatment on the treated was computed for each matching method. Observational data were analyzed for 185 early RA patients from the Western Consortium study followed six to sixty months (mean thirty-one months). For the selected index, 75 patients were categorized as nonprogressors; they had significantly lower disease activity, more clinical improvement and were treated earlier than the progressors. Of those treated within three months of symptom onset, 57% were classified as radiographically progressive versus 35% of those treated later ( P = 0.0058). However, after propensity score adjustment for baseline differences, we noticed nonsignificant ( P > 0.05) nonprogression in patients given earlier treatment. We conclude that propensity score analysis reduced but did not remove all bias.
Women's Ways of Knowing: It is All About Love!
Authors: Locatelli Carla
Published: April 2007

Love of knowledge is at the core of women's ways of knowing. The sustaining meditation of this article is the need to define in gynocentric terms what knowledge is, and how it can be formed, represented, and transmitted. The goal is to make this knowledge equally recognizable, just as the patriarchial knowledge secured by cultural memory is recognized and honoured. The relational ambivalence of love captures well both women's valorization of the relational quality of knowledge and the politics of desire that informs a feminist epistemology.
Weblog-Technology as a Trigger to Elicit Passion for Knowledge
Authors: Kaiser Stephan , Müller-Seitz Gordon , Pereira Lopes Miguel , Pina e Cunha Miguel
Published: April 2007

The practice of Weblogging as a new social and technological phenomenon in society and business is gaining a growing number of supporters. In short, a Weblog is a website where individual thoughts are publicly displayed in the form of a diary. In this paper, we seek to illustrate the impact of Weblog technology on people's passion for knowledge. We start from the assumption that successful knowledge management requires the engagement of people in knowledge-related practices. We introduce a famous agglomeration of Weblogs that deal with the development of a commercial software. Based on an exploratory study, we suggest that the specific features and character of this novel technology have an impact upon the passion for voluntary knowledge work, which is triggered by experiences of flow states, as well as extrinsic stimuli.
The Troubadours of Knowledge: Passion and Invention in Management Education
Authors: Dey Pascal , Steyaert Chris
Published: April 2007

This paper argues that current management education works primarily with an instrumental, reified and fragmented conception of knowledge that ignores the connection between knowing and passion. To propose a learning process that is less dispassionate and disembodied and that conceives of knowledge as invention, we first exemplify the current crises of (management) education and reflect on its implied concepts of knowledge and learning along Lyotard's principle of `performativity'. We further probe the relationship between passion and knowledge through Derrida's idea of the `unconditional university' and illustrate its merit for both critical reflection and affirmative invention. Instead of a nostalgic re-evocation of ancient pedagogies, we reflect critically upon the possibilities of a deconstruction-based pedagogy in contemporary management education and propose Serres' figure of the `troubadour of knowledge' as a conceptual persona that can guide us in developing learning practices that incorporate and combine the value of critique and invention.
Kinetics of mobilization and differentiation of lymphohematopoietic cells during experimental murine schistosomiasis in galectin-3−/− mice
Authors: Oliveira F L , Frazão P , Chammas R , Hsu D K , Liu F T , Borojevic R , Takiya C M , El-Cheikh M C
Published: April 2007

Galectin-3 (gal-3), a β-galactoside-binding animal lectin, plays a role in cell-cell and cell-extracellular matrix interactions. Extracellular gal-3 modulates cell migration and adhesion in several physiological and pathological processes. Gal-3 is highly expressed in activated macrophages. Schistosoma mansoni eggs display a large amount of gal-3 ligands on their surface and elicit a well-characterized, macrophage-dependent, granulomatous, inflammatory reaction. Here, we have investigated the acute and chronic phases of S. mansoni infection in wild-type and gal-3−/− mice. In the absence of gal-3, chronic-phase granulomas were smaller in diameter, displaying thinner collagen fibers with a loose orientation. Schistosoma-infected gal-3−/− mice had remarkable changes in the monocyte/macrophage, eosinophil, and B lymphocyte subpopulations as compared with the infected wild-type mice. We observed a reduction of macrophage number, an increase in eosinophil absolute number, and a decrease in B lymphocyte subpopulation (B220+/high cells) in the periphery during the evolution of the disease in gal-3−/− mice. B lymphopenia was followed by an increase of plasma cell number in bone marrow, spleen, and mesenteric lymph nodes of the infected gal-3−/− mice. The plasma IgG and IgE levels also increased in these mice. Gal-3 plays a role in the organization, collagen distribution, and mobilization of inflammatory cells to chronic-phase granulomas, niches for extramedullary myelopoiesis, besides interfering with monocyte-to-macrophage and B cell-to-plasma cell differentiation.
Postponement of Postmenopausal Mortality Acceleration in Low‐Mortality Populations
Authors: MILNE EUGENE M. G.
Published: April 2007

Abstract:  Mortality analyses commonly disregard postmenopausal acceleration. This study examined period log mortality in World Health Organization (WHO) data for 34 low‐mortality countries in 2000, demonstrating significant gradient increases for women (33/34 countries) and men (22/34), from a later age than previously reported, dividing the postmenopausal period into phases. “Break points” were identified as intersects of lines of best fit to these and the same approach was used in analysis of Human Mortality Database data for 19 countries. There has been an upward migration of about 10 years in female age at break point since 1850. Male data flipped from mortality acceleration to deceleration and back in the late 20th century with no apparent shift in break point. Altered age at mortality acceleration appears genuine, gender‐specific, and internationally consistent. Its timing prompts the hypothesis that it may relate to falling fertility.
Regulation of Human Life Histories
Authors: VAN BODEGOM DAVID , MAY LINDA , MEIJ HANS J. , WESTENDORP RUDI G. J.
Published: April 2007

Abstract:  Most species with a long life span have few offspring while species with a short life span have many offspring. This evolutionary trade‐off between fertility and body maintenance, based on the theory of r/K‐selection, is a central theme in the theory of life history regulation. This trade‐off is not only found between various species but also between individuals within one species. There is accumulating evidence for this trade‐off in humans. We hypothesize that the innate immune system is a critical factor skewing an individual into the direction of either a high fertility or better maintenance strategy. As over thousands of years human survival has been highly dependent on resistance to infectious diseases, genetic adaptations resulting in inflammatory responses were favored. An inflammatory host response is critical to fight infection necessary to survive up to reproductive age. An inflammatory host response is also negatively associated with fertility and can explain for the trade‐off between fertility and body maintenance. After human reproductive age, these inflammatory responses contribute also to development of chronic degenerative diseases. These will especially become apparent in affluent societies where the majority of individuals reach old age. Identifying the inflammatory host response as a critical factor both in the regulation of human life histories and in the occurrence of chronic diseases at old age implies means for intervention allowing individuals to live healthier for longer.
Do Membrane Rafts Contribute to Human Immunosenescence?
Authors: TOMOIU ANDRU , LARBI ANIS , FORTIN CARL , DUPUIS GILLES , FULOP TAMAS
Published: April 2007

Abstract:  Aging is associated with an alteration of the immune response called immunosenescence. It is now well accepted that all parts of the immune system, the adaptive as well as the innate, undergo immunosenescence. However, the adaptive immune response and especially T cell functions are the most affected by aging. Aging is associated with profound changes in lymphocytes subpopulations, however, the functional changes within these subsets are more important to elucidate. Indeed, T cells present functional modifications resulting in a decreased clonal expansion and interleukin‐2 (IL‐2) production. So there should be an alteration in the activation process of T cells with aging involving the T cell receptor (TCR) and CD28 receptor signaling cascades. The alterations in membrane rafts composition and function can underline this altered activation of T cells with aging and then contribute to human immunosenescence. The experimental data in favor of this hypothesis will be reviewed.
Chitotriosidase Levels in Healthy Elderly Subjects
Authors: KURT ISMAIL , ABASLI DILEK , CIHAN MURAT , SERDAR MUHITTIN A. , OLGUN ABDULLAH , SARUHAN ERCAN , ERBIL M. KEMAL
Published: April 2007

Abstract:  Chitotriosidase (CHIT) belongs to the family of glycosylhydrolases and is highly homologous to chitinases from lower organisms. The enzyme CHIT is of interest for clinical reasons, because it is selectively expressed in chronically activated tissue macrophages. In most ethnic groups, ∼6% of all individuals are homozygous for CHIT deficiency. Pathological tissue macrophages in several disease conditions massively express CHIT. A shared feature of such cells in the different conditions is the accumulation of lipid material in the lysosomal apparatus. Serum CHIT activity is significantly increased in individuals suffering from atherosclerosis disease and is related to the severity of the atherosclerotic lesion, suggesting a possible role as atherosclerotic extent marker. Our objective is to determine the levels of serum CHIT activity in healthy elderly subjects. Healthy 90 (between 65–94 years old) elderly people and 69 (between 20–44 years old) young people were chosen. Serum CHIT enzymatic activity was determined with the flurometric enzyme activity assay using artificial 4‐MU substrate. We found CHIT activity 270 ± 21 (nmol/mL/h) (values are mean ± SD) in elderly people and 136 ± 17 in young people. There are statistical differences between elderly and young subjects.
Genetic Variation in the Interleukin‐10 Gene Promoter and Risk of Coronary and Cerebrovascular Events
Authors: TROMPET S. , PONS D. , DE CRAEN A. J. M. , SLAGBOOM P. , SHEPHERD J. , BLAUW G. J. , MURPHY M. B. , COBBE S. M. , BOLLEN E.L.E.M. , BUCKLEY B. M. , FORD I. , HYLAND M. , GAW A. , MACFARLANE P. W. , PACKARD C. J. , NORRIE J. , PERRY I. J. , STOTT D. J. , SWEENEY B. J. , TWOMEY C. , WESTENDORP R. G. J. , JUKEMA J. W. ,   ON BEHALF OF THE PROSPER GROUP
Published: April 2007

Abstract:  Proinflammatory cytokines, like interleukin‐6 (IL‐6) and tumor necrosis factor‐alpha (TNF‐α), are implicated in the development of atherosclerosis. The role of anti‐inflammatory cytokines, like IL‐10, is largely unknown. We investigated the association of four single nucleotide polymorphisms (SNPs) in the promoter region of the IL‐10 gene (4259AG, −1082GA, −592CA, and −2849GA), with coronary and cerebrovascular disease in participants of the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) trial. All associations were assessed with Cox proportional hazards models adjusted for sex, age, pravastatin use, and country. Haplotype analysis of the four SNPs showed a significant association between haplotype 4 (containing the −592A variant allele) and risk of coronary events (P= 0.019). Moreover, analysis of separate SNPs found a significant association between −2849AA carriers with incident stroke (HR (95%CI) 1.50 (1.04–2.17), P value = 0.02). Our study suggests that not only proinflammatory processes contribute to atherosclerosis, but that also anti‐inflammatory cytokines may play an important role.
Antioxidant Enzymes and Diabetic Retinopathy
Authors: YILDIRIM ZUHAL , UÇGUN N. IREM , KILIÇ NEDRET , GÜRSEL E. , SEPICI‐DINÇEL AYLIN
Published: April 2007

Abstract:  The aim of this study was to discuss the serum copper (Cu), zinc (Zn), nitric oxide (NO), glutathione (GSH), advanced oxidation protein products (AOPP) levels, and superoxide dismutase (SOD) activities with diabetic retinopathy severity. Twenty‐five patients with proliferative diabetic retinopathy (PDR group 1), 25 patients with nonproliferative diabetic retinopathy (NPDR group 2), and 25 nondiabetic controls (control group) were included in the study. Patients who had macrovascular complications of diabetes (coronary arterial disease, periferic vascular disease) were excluded. The major finding of our study was that we did not observe any differences between group 1 and 2, which we aimed to discuss the severity of diabetic retinopathy. As the levels of SOD and Zn were not different between the groups, statistically significant differences were observed for GSH, NO, and Cu levels when compared to control group. AOPP levels were statistically increased in group 1 compared to control group. It can be suggested that hyperglycemia in DM is associated with accelerated nonenzymatic glycation and oxidative stress.
Evaluation of Measurement Uncertainty of Glucose in Clinical Chemistry
Authors: BERÇIK İNAL B. , KOLDAŞ M. , İNAL H. , COŞKUN C. , GÜMÜŞ A. , DÖVENTAŞ Y.
Published: April 2007

Abstract:  The definition of the uncertainty of measurement used in the International Vocabulary of Basic and General Terms in Metrology (VIM) is a parameter associated with the result of a measurement, which characterizes the dispersion of the values that could reasonably be attributed to the measurand. Uncertainty of measurement comprises many components. In addition to every parameter, the measurement uncertainty is that a value should be given by all institutions that have been accredited. This value shows reliability of the measurement. GUM, published by NIST, contains uncertainty directions. Eurachem/CITAC Guide CG4 was also published by Eurachem/CITAC Working Group in the year 2000. Both of them offer a mathematical model, for uncertainty can be calculated. There are two types of uncertainty in measurement. Type A is the evaluation of uncertainty through the statistical analysis and type B is the evaluation of uncertainty through other means, for example, certificate reference material. Eurachem Guide uses four types of distribution functions: (1) rectangular distribution that gives limits without specifying a level of confidence (u(x)=a/√3) to a certificate; (2) triangular distribution that values near to the same point (u(x)=a/√6); (3) normal distribution in which an uncertainty is given in the form of a standard deviation s, a relative standard deviation s/√n, or a coefficient of variance CV% without specifying the distribution (a = certificate value, u = standard uncertainty); and (4) confidence interval.
Mitochondrial DNA Mutations and Aging
Authors: KRISHNAN KIM J. , GREAVES LAURA C. , REEVE AMY K. , TURNBULL DOUGLASS M.
Published: April 2007

Abstract:  Mitochondria have been hypothesized to play a role in both aging and neurodegenerative diseases, such as Parkinson's disease (PD) and Alzheimer's disease. Many studies have shown the accumulation of mitochondrial DNA (mtDNA) mutations in post‐mitotic tissues and more recent data have shown this also to be a feature of aging mitotic tissues. Much of this data has been correlative, until recently with the development of polymerase gamma deficient mice which accumulate high levels of mtDNA mutations and show a premature aging phenotype, that a more causative role has been proposed. This article focuses on recent developments in aging research into the role that mtDNA mutations play in the aging process.
Mitochondrial DNA‐Deficient Models and Aging
Authors: OLGUN ABDULLAH , AKMAN SERIF
Published: April 2007

Abstract:  Human mitochondrial DNA (mtDNA) encodes 13 subunits of oxidative phosphorylation (OXPHOS) enzyme complexes I, III, IV, and V except complex II. MtDNA is more sensitive to oxidative damage than nuclear DNA. MtDNA defects are involved in many pathologies including aging. Several mtDNA‐deficient cell culture, yeast, and animal models were generated to study the role of mtDNA in many physiological processes. Ethidium bromide (EB), an agent that is known to inhibit mtDNA replication with a negligible effect on nuclear DNA, is generally used to generate mtDNA‐deficient models. The antibiotics chloramphenicol and doxycycline, which were known to inhibit mitochondrial translation, were also used to generate the same phenotype. Cultured mtDNA‐deficient cells need uridine and pyruvate to survive. At the organismal level, uridine can be supplemented, but pyruvate supplementation can cause a worser phenotype because of lactic acidosis. In C. elegans, EB, when used during larval development, increases life span, but decreases, when used after the beginning of adult stage. This should be kept in mind since mitochondria‐related genes are generally detected in genome‐wide screening studies for longevity. We believe that conditional knockout studies need to be carried out for these genes after reaching adulthood. MtDNA mutator mouse did not show an increase of free radical production. Therefore, the downstream phenomena to mtDNA defects are likely ineffective pyrimidine synthesis (dihydroorotate dehydrogenase, DHODH, needs a functional respiratory chain) and excess NADH (decreased NAD pool) in addition to free radicals.
Alterations to Nuclear Architecture and Genome Behavior in Senescent Cells
Authors: MEHTA ISHITA S. , FIGGITT MARTIN , CLEMENTS CRAIG S. , KILL IAN R. , BRIDGER JOANNA M.
Published: April 2007

Abstract:  The organization of the genome within interphase nuclei, and how it interacts with nuclear structures is important for the regulation of nuclear functions. Many of the studies researching the importance of genome organization and nuclear structure are performed in young, proliferating, and often transformed cells. These studies do not reveal anything about the nucleus or genome in nonproliferating cells, which may be relevant for the regulation of both proliferation and replicative senescence. Here, we provide an overview of what is known about the genome and nuclear structure in senescent cells. We review the evidence that nuclear structures, such as the nuclear lamina, nucleoli, the nuclear matrix, nuclear bodies (such as promyelocytic leukemia bodies), and nuclear morphology all become altered within growth‐arrested or senescent cells. Specific alterations to the genome in senescent cells, as compared to young proliferating cells, are described, including aneuploidy, chromatin modifications, chromosome positioning, relocation of heterochromatin, and changes to telomeres.
Proteasome and Photoaging
Authors: BULTEAU ANNE‐LAURE , MOREAU MARIELLE , NIZARD CARINE , FRIGUET BERTRAND
Published: April 2007

Abstract:  Cellular aging is characterized by the accumulation of oxidatively modified proteins that result, at least in part, from impaired degradation of abnormal proteins. The proteasome is the major intracellular proteolytic system implicated in the removal of abnormal and oxidized proteins. In human epidermal cells, previous studies have evidenced that proteasome function is decreased during aging as well as upon UV irradiation, which is the main component of photoaging. The age‐related decline of proteasome activity has been reported to be due to either or both decreased proteasome subunits expression and content, inactivation upon alteration of proteasome subunits, and accumulation of endogenous inhibitors, such as highly oxidized and cross‐linked proteins. To gain further insight in the mechanisms that might be implicated in the decreased activity of the proteasome upon photoaging, purified 20S human proteasome has been exposed to UVA‐ and UVB‐irradiation. The effect of such an irradiation on proteasome peptidase activities has been monitored and shown to promote a stimulation or an inhibition of the peptidase activities depending on whether the proteasome is under its latent or a nonphysiological active form. Analysis of the patterns of proteasome subunits by 2D gel electrophoresis has revealed modification for several subunits for UV‐irradiated proteasome only in its irreversibly activated form, compared with nonirradiated and irradiated latent forms, indicating that the 20S proteasome is rather resistant to UV irradiation.
Methionine Sulfoxide Reduction and the Aging Process
Authors: KOC AHMET , GLADYSHEV VADIM N.
Published: April 2007

Abstract:  Aging has been described for multicellular and asymmetrically dividing organisms, but the mechanisms are poorly understood. Oxidation of proteins is considered to be one of the major factors that leads to aging. Oxidative damage to proteins results in the oxidation of certain amino acid residues, among which oxidation of sulfur‐containing amino acids, methionine and cysteine, is notable because of the susceptibility of these residues to damage, and occurrence of repair mechanisms. Methionine sulfoxide reductases, MsrA and MsrB, are thioredoxin‐dependent oxidoreductases that reduce oxidized forms of methionine, methionine sulfoxides, in a stereospecific manner. These enzymes are present in all cell types and have shown to be regulating life spans in mammals, insects, and yeast. Here, their roles in modulating yeast life span are discussed.
Activation of Pericentromeric and Telomeric Heterochromatin in Cultured Lymphocytes from Old Individuals
Authors: LEZHAVA TEIMURAZ , JOKHADZE TINA
Published: April 2007

Abstract:  The functional characteristics of chromosomes (level of total heterochromatin, chromosome instability, and sister chromatid exchanges [SCEs]) were studied in cultured lymphocytes derived from 80‐ to 91‐year‐old and 18‐ to 30‐year‐old (control group) individuals under the single and combined effect of CoCl2 and bioregulator Livagen. The results obtained showed that chromosome heterochromatinization (condensation of eu‐ and heterochromatin regions) had progressively increased with aging and led to inactivation of a number of once functioning “active genes.” The peptide bioregulator Livagen could induce reactivation (deheterochromatinization) of chromatin to modify heterochromatinized chromosomal regions in cultured lymphocytes of aged individuals. Our results indicated that metal ions (CoCl2) caused a significant increase in the level of chromosomal aberrations in old donors in comparison with the control group (P < 0.05). The peptide bioregulator Livagen was effective in decreasing the number of changes induced by the CoCl2 3.4 ± 0.6% (control group 4.2 ± 0.7%). Co2+ ions single and Co2+ ions in combination with the Livagen changed the distribution of SCE over chromosomes: pericentromeric heterochromatin was more sensitive to the effect of CoCl2 (15.4 ± 1.8% SCE), while SCE were mostly registered in telomeric heterochromatin under the combined effect of CoCl2 and Livagen 12.0 ± 1.2% SCE (control group 4.5 ± 0.6% and 2.8 ± 0.5% SCE, respectively). Thus, we have first demonstrated that Co2+ ions separately and in combination with the bioregulator Livagen have different chromosomal target regions as demonstrated by SCE induction, deheterochromatinization of precentromeric and telomeric heterochromatin in lymphocytes from old individuals.