bluuebunny/crossref_metadata_2025 huggingface dataset:
Getting from A to IRB: Developing an Institutional Review Board at a Historically Black University
Authors: Howard Daniel L. , Boyd Carlton L. , Nelson Daniel K. , Godley Paul
Published: March 2010

Shaw university, the oldest historically black college or university in the southern USA, recently partnered with the University of North Carolina at Chapel Hill, a major research institution in North Carolina, to further develop Shaw's research infrastructure. One aim of the partnership involved establishing a human research ethics committee and an accompanying administrative structure and research ethics education program. This paper describes the process of developing an entire human research protection program de novo through collaboration with and mentoring by the members of the human research protection program at a nearby major research institution. This paper provides a detailed description of the aims, procedures, accomplishments, and challenges involved in such a project, which may serve as a useful model for other primarily teaching institutions wishing to develop research infrastructure and ethical capacity.
Cyclophilin B as a co-regulator of prolactin-induced gene expression and function in breast cancer cells
Authors: Fang Feng , Zheng Jiamao , Galbaugh Traci L , Fiorillo Alyson A , Hjort Elizabeth E , Zeng Xianke , Clevenger Charles V
Published: March 2010

The effects of prolactin (PRL) during the pathogenesis of breast cancer are mediated in part though Stat5 activity enhanced by its interaction with its transcriptional inducer, the prolyl isomerase cyclophilin B (CypB). We have demonstrated that knockdown of CypB decreases cell growth, proliferation, and migration, and CypB expression is associated with malignant progression of breast cancer. In this study, we examined the effect of CypB knockdown on PRL signaling in breast cancer cells. CypB knockdown with two independent siRNAs was shown to impair PRL-induced reporter expression in breast cancer cell line. cDNA microarray analysis was performed on these cells to assess the effect of CypB reduction, and revealed a significant decrease in PRL-induced endogenous gene expression in two breast cancer cell lines. Parallel functional assays revealed corresponding alterations of both anchorage-independent cell growth and cell motility of breast cancer cells. Our results demonstrate that CypB expression levels significantly modulate PRL-induced function in breast cancer cells ultimately resulting in enhanced levels of PRL-responsive gene expression, cell growth, and migration. Given the increasingly appreciated role of PRL in the pathogenesis of breast cancer, the actions of CypB detailed here are of biological significance.
Estradiol and Metabolic Syndrome in Older Italian Men: The InCHIANTI Study
Authors: Maggio Marcello , Lauretani Fulvio , Ceda Gian Paolo , Bandinelli Stefania , Basaria Shehzad , Paolisso Giuseppe , Giumelli Claudio , Luci Michele , Najjar Samer S. , Metter E. Jeffrey , Valenti Giorgio , Guralnik Jack , Ferrucci Luigi
Published: March 2010

ABSTRACT: The increasing prevalence of metabolic syndrome (MS) with age in older men has been linked with decreasing testosterone levels. Interestingly, while testosterone levels decline with age, estradiol (E2) levels remain relatively stable, resulting in a decreased testosterone: E2 ratio. Because E2 levels tend to be elevated in morbid obesity, insulin resistance, and diabetes, it is reasonable to hypothesize that high E2 levels are associated with MS in older men. We studied the relationship of total and free E2 with MS after adjustment for multiple confounders, including age, BMI, smoking, alcohol consumption, physical activity, interleukin‐6 (IL‐6), fasting insulin, and testosterone. Men 65 years or older (age range, 65–96; n = 452) had complete data on E2, testosterone, fasting insulin, sex hormone–binding globulin, IL‐6, and albumin. Concentrations of free E2 and free testosterone were calculated using the mass action equations. MS was defined according to Adult Treatment Panel III (ATP‐III). Participants with MS had significantly higher serum free and total E2 (P < .001) (P = .003). After adjusting for confounders, including age, smoking, alcohol consumption, physical activity, log(IL‐6), and log(insulin), participants with higher log(total E2) (odds ratio [OR], 2.31; 95% confidence interval [95% CI], 1.39–4.70; P = .02) and higher log(free E2) (OR, 2.69; 1.38–5.24; P < .001) had an increased risk of having MS. Log(free E2) (P = .04) maintained significant correlation with MS, even after further adjustment for BMI. In older men, high E2 is independently associated with MS. Whether confirmed in other studies, assessment of E2 should be also considered in older men. Whether changes in this hormonal pattern play a role in the development of MS should be further tested in longitudinal studies.
The Mechanistic Basis for Sexual Dysfunction in Male Transforming Growth Factor β1 Null Mutant Mice
Authors: Ingman W. V. , McGrath L. M. , Breed W. G. , Musgrave I. F. , Robker R. L. , Robertson S. A.
Published: March 2010

ABSTRACT:The cytokine transforming growth factor β1 (TGFB1) is implicated in male sexual function. Previous behavioral studies show thatTgfb1null mutant mice mount and display limited intromission behavior with receptive females but are unable to complete successful copulation. The studies presented here explore the physiologic basis for sexual dysfunction inTgfb1null mutant males. Scanning electron microscopy revealed that the surface of the penis inTgfb1null mutant males was abnormally coated in superficial keratinized epithelial cells. There was a significant reduction in protrusion of penile spines through the superficial tissue inTgfb1null mutant mice; in some mice, the spines were almost completely embedded. Histologic analysis revealed reduced skin thickness in the penis ofTgfb1null mutant males. Nerve fibers, endothelial cells, smooth muscle actin, macrophages, and neuronal and inducible nitric oxide synthase were present in similar abundance and location inTgfb1null mutant mice compared with wild‐type controls; however, an increase in collagen I deposition was detected. Behavioral studies revealed thatTgfb1null mutant males undergo spontaneous noncontact erections, albeit at a reduced rate compared with control mice, and engage in less frequent genital grooming activity. These studies suggest thatTgfb1null mutation may adversely influence copulatory behavior through effects on both altered structural integrity of the penile skin and impaired tissue compliance leading to erectile dysfunction.
Identification of Acrosomal Matrix–Specific Hydrolases Binding Proteins of Bovine Cauda Epididymal Spermatozoa
Authors: Nagdas Subir K. , Hamilton Shatasha L. , Raychoudhury Samirsubas
Published: March 2010

ABSTRACT: Previously, we described the isolation of a detergent‐stable complex from bovine sperm acrosome, termed the outer acrosomal membrane–associated matrix complex (OMC). This stable matrix assembly is associated with the luminal surface of the outer acrosomal membrane and exhibits specific binding activity for acrosin. The present study was undertaken to identify the matrix proteins that specifically interact with acrosomal hydrolases. The OMC fraction exhibited polypeptides of 54, 50, and 45 kd and a major polypeptide family between 38 and 19 kd by sodium dodecyl sulfate polyacrylamide gel electrophoresis. In this study, we purified 45‐kd polypeptide, termed OMC45, from the high–pH insoluble fraction of OMC, and the polyclonal antibody was raised against 45‐kd polypeptide. Anti‐OMC45 polyclonal antibody reacts strongly on immunoblots with the OMC45 band. Using immunofluorescence anti‐OMC45 localizes specifically to the acrosomal cap. Two‐dimensional polyacrylamide gel electrophoresis and immunoblot analysis of OMC identified a set of approximately 5–6 isoelectric variants of 45 kd in the pH range of 5.5–7.2. To identify matrix‐specific hydrolase‐binding proteins, OMC32 (32‐kd polypeptide isolated from high‐pH soluble fraction of OMC) and OMC45 polypeptides were coupled to AminoLink Plus resin separately and incubated with soluble acrosomal hydrolases. Acrosin and N‐acetylglucosaminidase bound the OMC32 polypeptide in a concentration‐dependent fashion. In contrast, OMC45 polypeptide exhibited stronger affinity to acrosin than N‐acetylglucosaminidase. The binding specificity of acrosomal matrix proteins to hydrolases strongly suggests that the matrix polypeptides play an important role in the regulation of hydrolase release during the acrosome reaction and could also function during acrosome assembly to target and/or segregate hydrolases within the acrosome interior.
Seminal Plasma Proteins as Potential Markers of Relative Fertility in Boars
Authors: Novak Susan , Ruiz‐Sánchez Ana , Dixon Walter T. , Foxcroft George R. , Dyck Michael K.
Published: March 2010

ABSTRACT: This study investigated whether specific proteins from distinct seminal plasma fractions of boars could be related to in vivo fertility. Nine boars with acceptable sperm motility and morphology for use in artificial insemination demonstrated major differences in total number born and pregnancy rate when low sperm doses (1.5 billion sperm) were used to breed a minimum of 50 gilts per boar. The 2 lowest‐fertility and 2 highest‐fertility boars were chosen for evaluation of specific seminal plasma proteins. On 4 occasions, semen was collected and separated into 3 fractions based on sperm concentration (Sperm‐Peak, Sperm‐Rich, and Sperm‐Free), and the fractions were analyzed for total protein concentration and abundance of major seminal plasma glycoprotein (PSP‐I), AWN‐1, and osteopontin protein using Western blotting techniques. The concentrations of these seminal plasma proteins were lower in the Sperm‐Peak fractions compared with the Sperm‐Free fractions (P < .05). Seminal plasma from the pooled Sperm‐Rich fraction used for artificial insemination was also subjected to two‐dimensional gel electrophoresis to investigate novel protein markers related to in vivo fertility. Total piglets born (r = −0.76, P = .01) and sperm motility at day 7 (r = −0.74, P = .037) were again negatively correlated with a 22‐kDa protein identified by mass spectrometry as PSP‐I. However, fertility index and farrowing rate tended to be positively correlated (P < .10) with a 25‐kDa protein, identified as glutathione peroxidase (GPX5), an antioxidant enzyme that may protect sperm membranes from oxidative damage. These candidate proteins merit further investigation as markers of fertility in boars.
Nanobacteria May Be Linked to Testicular Microlithiasis in Infertility
Authors: Zhang Qing‐Hua , Lu Gen‐Sheng , Shen Xue‐Cheng , Zhou Zhan‐Song , Fang Qiang , Zhang Xin , Li Long‐Kun , Jin Xi‐Yu , Song Bo
Published: March 2010

ABSTRACT: Testicular microlithiasis (TM) in infertility is an uncommon pathologic condition of unclear etiology that is characterized by calcium deposits within the seminiferous tubules. Nanobacteria (NB), as novel microorganisms mediating tissue calcification, have been discovered in some diseases. In this study, we hypothesized that NB may participate in the pathogenesis of TM, particularly in infertility. Seventeen infertility patients with TM detected by scrotal color Doppler ultrasonography and 17 infertility patients without TM as controls were enrolled in the study. The NB were isolated and cultured from semen samples and urine samples. After 3 to 6 weeks of culture, 10 of 17 (58.8%) semen samples and 2 urine samples from infertile patients with TM showed the growth of white granular microbes that firmly attached to the bottom of the culture flask and were visible to the naked eye. In the control group, only 1 of 17 (5.9%) semen samples from infertile patients without TM showed the growth of white granular microbes. The cultured microbes were identified by indirect immunofluorescent staining (IIFS), transmission electron microscopy (TEM), and 16s rRNA gene expression. IIFS and TEM revealed NB to be coccoid and 100 to 500 nm in diameter. The BLAST result revealed that the 16s rRNA gene sequence from the cultured microbes was 97% the same as that of the known NB. Our results showed that NB may be linked to the development of TM, which may provide a potential target for the diagnosis and treatment of infertility with TM.
Late Delayed Repair of Fractured Penis
Authors: Naraynsingh Vijay , Hariharan Seetharaman , Goetz Lester , Dan Dilip
Published: March 2010

ABSTRACT: Early surgery has been recommended by most authors for fractured penis. Because of gross swelling of the penis, early surgery might have to be performed with an extensive degloving incision of the penis to enable better exposure. We report a case in which the man presented late with deformity and pain. Simple repair at that stage provided a good result in this patient; hence, it might be possible to repair a fractured penis at a later stage without degloving the penis. Additionally, this presentation could probably explain the pathogenesis of the “rolling sign” described by us earlier.
The Association of Serum Prolidase Activity and Erectile Dysfunction
Authors: Savas M. , Yeni E. , Celik H. , Ciftci H. , Utangac M. , Oncel H. , Altunkol A. , Verit A.
Published: March 2010

ABSTRACT: Prolidase is a cytosolic exopeptidase that cleaves iminodipeptides with carboxy‐terminal proline or hydroxyproline and plays a major role in collagen turnover. Collagen is the essential content in atherosclerotic plaque, playing a key role in the stability/instability and progression of endothelial dysfunction in the pathogenesis of erectile dysfunction (ED). Consequently, in this study we sought to determine serum prolidase activity and markers of oxidative stress, such as lipid hydroperoxide and total free sulfhydryl, in vasculogenic ED. We evaluated 92 patients with vasculogenic ED and 50 control subjects by clinical and laboratory investigations. We measured serum prolidase activity and serum total free sulfhydryl levels spectrophotometrically. Serum lipid hydroperoxide levels were determined with ferrous ion oxidation‐xylenol orange method. We assessed the association of serum prolidase activity with the presence and severity of vasculogenic ED and clinical characteristics, as well as laboratory parameters. We also assessed the association of serum prolidase activity with the variables according to the vascular status of patients with vasculogenic ED. The comparison included 92 vasculogenic ED patients grouped into 3 categories according to the vascular status of patients with ED—arterial insufficiency (n = 26), veno‐occlusive dysfunction (n = 37), and mixed‐type impotence (n = 29)—and 50 controls. Receiver‐operator characteristics (ROCs) were analyzed to find a cutoff value with the best sensitivity and lowest false‐positive rate. Serum prolidase activity (53.5 ± 5.5 U/L vs 45.7 ± 4.9 U/L, respectively; P < .001) and serum lipid hydroperoxide levels were significantly increased in patients with vasculogenic ED compared with controls, whereas serum total free sulfhydryl levels were significantly decreased in patients with vasculogenic ED compared with controls (P < .001). The lowest and highest mean serum prolidase activities were detected in control participants and in patients with arterial insufficiency, respectively (analysis of variance P < .001). The overall findings of this study support the predictive accuracy of the serum prolidase activity in our cohort, with a statistically significant ROC value of 0.78. Findings of this study have shown that serum prolidase activity is significantly associated with the presence and severity of vasculogenic ED, and elevated serum prolidase activity might be an independent predictor of ED.
Some natural decision problems in automatic graphs
Authors: Kuske Dietrich , Lohrey Markus
Published: March 2010

For automatic and recursive graphs, we investigate the following problems:

(A) existence of a Hamiltonian path and existence of an infinite path in a tree

(B) existence of an Euler path, bounding the number of ends, and bounding the number of infinite branches in a tree

(C) existence of an infinite clique and an infinite version of set cover

The complexity of these problems is determined for automatic graphs and. supplementing results from the literature, for recursive graphs. Our results show that these problems

(A) are equally complex for automatic and for recursive graphs (-complete).

(B) are moderately less complex for automatic than for recursive graphs (complete for different levels of the arithmetic hierarchy),

(C) are much simpler for automatic than for recursive graphs (decidable and -complete, resp.).
A computable ℵ0-categorical structure whose theory computes true arithmetic
Authors: Khoussainov Bakhadyr , Montalbán Antonio
Published: March 2010

We construct a computable ℵ0-categorical structure whose first order theory is computably equivalent to the true first order theory of arithmetic.
Employment Relations and Global Health: A Typological Study of World Labor Markets
Authors: Chung Haejoo , Muntaner Carles , Benach Joan ,   EMCONET Network
Published: March 2010

In this study, the authors investigate the global labor market and employment relations, which are central building blocks of the welfare state; the aim is to propose a global typology of labor markets to explain global inequalities in population health. Countries are categorized into core (21), semi-peripheral (42), and peripheral (71) countries, based on gross national product per capita (Atlas method). Labor market–related variables and factors are then used to generate clusters of countries with principal components and cluster analysis methods. The authors then examine the relationship between the resulting clusters and health outcomes. The clusters of countries are largely geographically defined, each cluster with similar historical background and developmental strategy. However, there are interesting exceptions, which warrant further elaboration. The relationship between health outcomes and clusters largely follows the authors' expectations (except for communicable diseases): more egalitarian labor institutions have better health outcomes. The world system, then, can be divided according to different types of labor markets that are predictive of population health outcomes at each level of economic development. As is the case for health and social policies, variability in labor market characteristics is likely to reflect, in part, the relative strength of a country's political actors.
Unemployment, Informal Work, Precarious Employment, Child Labor, Slavery, and Health Inequalities: Pathways and Mechanisms
Authors: Muntaner Carles , Solar Orielle , Vanroelen Christophe , Martínez José Miguel , Vergara Montserrat , Santana Vilma , Castedo Antía , Kim Il-Ho , Benach Joan ,   EMCONET Network
Published: March 2010

The study explores the pathways and mechanisms of the relation between employment conditions and health inequalities. A significant amount of published research has proved that workers in several risky types of labor—precarious employment, unemployment, informal labor, child and bonded labor—are exposed to behavioral, psychosocial, and physio-pathological pathways leading to physical and mental health problems. Other pathways, linking employment to health inequalities, are closely connected to hazardous working conditions (material and social deprivation, lack of social protection, and job insecurity), excessive demands, and unattainable work effort, with little power and few rewards (in salaries, fringe benefits, or job stability). Differences across countries in the social contexts and types of jobs result in varying pathways, but the general conceptual model suggests that formal and informal power relations between employees and employers can determine health conditions. In addition, welfare state regimes (unionization and employment protection) can increase or decrease the risk of mortality, morbidity, and occupational injury. In a multilevel context, however, these micro- and macro-level pathways have yet to be fully studied, especially in middle- and low-income countries. The authors recommend some future areas of study on the pathways leading to employment-related health inequalities, using worldwide standard definitions of the different forms of labor, authentic data, and a theoretical framework.
Titrimetric and spectrophotometric determination of doxycycline hyclate using bromate-bromide, methyl orange and indigo carmine
Authors: Ramesh Jagannathamurthy , Basavaiah Kanakapura , Divya Ranganath , Rajendraprasad Nagaraju , Vinay Basavaiah
Published: March 2010

One titrimetric and two indirect spectrophotometric methods are described for the determination of doxycycline hyclate (DCH) in bulk drug and in its formulations. The methods use bromate-bromide, methyl orange and indigo carmine as reagents. In titrimetry (method A), DCH is treated with a known excess of bromate-bromide mixture in acid medium and the residual bromine is back titrated iodometrically after the reaction between DCH and in situ bromine is ensured to be complete. In spectrophotometric methods, the excess of bromine is estimated by treating with a fixed amount of either methyl orange (method B) or indigo carmine (method C) and measuring the change in absorbance either at 520 or 610 nm. Titrimetric method is applicable over 1-8 mg range and the calculations are based on a 1:2 (DCH:bromate) stoichiometric ratio. In spectrophotometry, the calibration graphs were found to be linear over 0.25-1.25 and 1-5 ?g mL-1 for method B and method C, respectively, with corresponding molar absorptivity values of 2.62 ?105 and 6.97 ? 104 L mol-1 cm-1. Accuracy and precision of the assays were determined by computing the intra-day and inter-day variations at three different levels of DCH.
Drying of immobilized yeast cells in spouted bed dryer with a moving draft tube
Authors: Povrenovic Dragan , Nedovic Viktor
Published: March 2010

Brewery yeast cells immobilized in Ca-alginate were dried in a laboratory scale spouted bed with a draft tube The experiment was conducted under variable temperatures and air flow rates. Temperature and air velocity at the bottom of the column has been varied in the range from 30 to 60 oC and from 6 to 10 m/s in a duration of 60 minutes. The moisture of dryied particles was in the interval of 10.00 to 21.00 g/g , while the water activity was in the range of 0.40 to 0.45, what ensures preservation of immobilized yeast as a starter and provides the biological activity of dried particles. Rehidration process of dryied particles, proved that dried particles could restore completely their original shape and starting volume, while the mechanical resistance is somewhat reduced. The cells preserved in this way after rehidration completely restore their catalytical activity.
Asleep at the Wheel: Pharmacy Practice Research Advocacy and Knowledge Translation by Canadian Pharmacy Organizations
Authors: Truong Kalena , Rosenthal Meagen , Tsuyuki Ross T.
Published: March 2010

Background:

The Blueprint for Pharmacy clearly articulates the need and imperative for pharmacy practice to move toward patient-centred care. Pharmacy professional organizations have a crucial role to play in this change, through leadership, communication and advocacy. This survey aimed to determine what knowledge translation (KT) activities were performed by Canadian pharmacy professional organizations in relation to a major pharmacy practice study.

Methods:

We sent a letter summarizing the findings and implications of the recently published hypertension trial, SCRIP- HTN, to the leaders of each pharmacy regulatory and advocacy body in Canada. Six months later, we followed up with these groups to inquire about KT activities that had been performed around the study findings.

Results:

Of the 22 organizations, 3 performed some type of KT activity. The major barrier to KT cited by the regulatory bodies was that it was not their job. The most common reason given by the advocacy bodies was that the study or its implications were not a priority. Other barriers included lack of time, lack of resources and political issues.

Conclusion:

KT and advocacy by our pharmacy professional organizations was practically nonexistent. This must change if we are to put into effect the vision of the Blueprint for Pharmacy for pharmacy practice change and optimal patient care.
Être entrepreneur de soi-même après la loi du 4 août 2008 : les impasses d'un modèle productif individuel
Authors: Levratto Nadine , Serverin Évelyne
Published: March 2010

La loi de modernisation de l’économie du 4 août 2008 a voulu introduire un nouveau statut d’entrepreneur individuel, l’auto-entrepreneur, avec l’objectif déclaré de soutenir une politique économique conjuguant lutte contre le chômage, recherche de points de croissance et amélioration du pouvoir d’achat. Le propos de cet article est de mettre en discussion le modèle de l’auto-entrepreneur qui sous-tend ce texte, en adoptant un double point de vue : juridique sur le modèle du travail, économique sur le modèle de l’entreprise. La première section discute la proclamation d’indépendance de l’auto-entrepreneur, en mettant en évidence l’existence de multiples dépendances juridiques, dans le cadre du cumul d’activités d’une part, dans l’exercice même de l’activité productive d’autre part ; la seconde section s’attache aux tensions existant entre la structure de l’auto-entreprise et, d’une part les objectifs de croissance des entreprises, d’autre part les théories de l’entreprise et de l’entrepreneur.
L'« activité économique », un critère d'applicabilité du droit de la concurrence rebelle à la conceptualisation
Authors: Bernard Elsa
Published: March 2010

Parce qu’elle poursuit une finalité précise – en l’occurrence délimiter le champ d’application du droit de la concurrence –, la notion fonctionnelle d’activité économique ne peut être que contingente. Sa conceptualisation étant illusoire, elle sert, en droit, de « prétexte juridiquement correct » pour identifier les activités soumises aux règles de la concurrence et celles qui leur échappent. Le recours au critère de l’activité économique peut s’expliquer par la nécessité de poser des limites juridiques à un domaine par essence économique : le marché. S’il est en effet souhaitable que le droit de la concurrence soit appliqué à divers types d’échanges sociaux, il est indispensable que d’autres échanges échappent, compte tenu de leur nature, aux règles du marché. Il s’agit alors de circonscrire l’applicabilité du droit de la concurrence à un ordre et d’en préserver les autres, afin que la logique du marché ne s’étende pas au-delà des limites souhaitées par le pouvoir politique. C’est donc la nécessité de soumettre certaines situations aux lois du marché ou, au contraire, de les en protéger qui conditionne, implicitement, la conception que les autorités de la concurrence et le juge retiennent de l’activité économique. Cette démarche finaliste explique que la notion reste rebelle à toute conceptualisation.
Propriété intellectuelle, concurrence et régulation – limites de protection et limites de contrôle
Authors: Ullrich Hanns
Published: March 2010

Dans l’Union européenne, la politique de concurrence relative aux pratiques restrictives liées à l’exercice des droits de propriété intellectuelle a considérablement changé d’orientation. Alors que dans le domaine des pratiques contractuelles et concertées (Art. 81 Traité CE), les accords de licence, dits de « transfert de technologie » bénéficient d’une généreuse exemption par catégorie, et que les communautés de brevets sont évaluées de façon bienveillante, les pratiques unilatérales (Art. 82 Traité CE), notamment les refus de licence et même les stratégies de prise de brevets, sont considérées d’un œil vigilant. Il en résulte non seulement des contradictions, mais aussi un potentiel accru de conflits entre l’autonomie d’acquisition et d’exploitation des droits exclusifs et les règles de concurrence, lequel demande un réexamen des rapports entre le système de protection de la propriété intellectuelle, notamment le système de la protection par brevets, et le droit de la concurrence. Contrairement à l’idée reçue sur l’existence de rapports de complémentarité entre les finalités du système de la propriété intellectuelle et les règles de concurrence, l’auteur considère l’octroi et la protection de droits exclusifs comme constituant un sous-système de l’ordre concurrentiel, dont le but est de permettre et de promouvoir une concurrence inter-technologies, que le droit de la concurrence est censé protéger contre toute pratique anticoncurrentielle. En tant que tel, le but du droit contre les restrictions à la concurrence n’est ni de corriger le système de protection en général ou au cas par cas, ni d’en compenser les déficits éventuels. Plus exactement, une telle « régulation » de la protection ne peut être accomplie que par la bonne configuration et la judicieuse mise en œuvre du système de propriété, de ses limites et de ses « exceptions » internes. C’est à cette fin que l’auteur développe en matière de protection de la propriété intellectuelle l’idée d’une approche fonctionnaliste et contextuelle de l’interprétation de la portée et de la réalisation de la finalité de cette protection. Cette approche permettrait de mieux comprendre et de cerner avec plus de précision l’autonomie d’acquisition et d’exploitation des droits exclusifs. Cette thèse est illustrée par une nouvelle approche des conflits entre le droit des brevets et la normalisation technique dite « ouverte ».
Lessons from Europe for China? New Urban Sub-Centres for a Polycentric Network City
Authors: Lehmann Steffen
Published: March 2010

This paper compares two cases: It relates to the development of new urban sub-centres in China, and the relationship of these sub-centres to ‘Network City’ theory. As cities move towards more polycentric systems, the case of Potsdamer Platz Berlin, compared to Zhenru Sub-Centre in Shanghai, is discussed. Both are transport-oriented developments promoting mixed-use density and transport-oriented development. According to the documentation by Shanghai municipality, this new urban centre, which is currently in its planning phase, is supposed to become a ‘sustainable sub-centre for a growing metropolis.’ The author, who has intimate knowledge of the Berlin case, was asked to advice on the Chinese project, based on the Potsdamer Platz experience. After some hesitation, a series of careful recommendations were formulated for the design and development of the Zhenru Sub-Centre, knowing that it is rather difficult to translate from one case to the other. The conclusion includes five recommendations for the urban design of such sub-centres, to ensure a delivery of economical, social and environmental sustainable outcomes.
Lck Mediates Th2 Differentiation through Effects on T-bet and GATA-3
Authors: Kemp Kyeorda L. , Levin Steven D. , Bryce Paul J. , Stein Paul L.
Published: March 2010

The Src family kinase Lck has been shown to be crucial in T cell signaling and development. However, its role in Th effector functions is not well understood. Lck has previously been shown to play a role in the cytokine expression of Th2 cells, but the mechanism by which Lck influences Th2 effector functions is unknown. Using a mouse model, we report that Lck is important in regulating the expression of IL-4 in Th2 skewed cells but is not as necessary for the expression of Th2 cytokines IL-5, IL-10, and IL-13. Furthermore, in the absence of Lck, T-bet and GATA-3 expression is aberrant. Moreover, this atypical expression pattern of T-bet and GATA-3 correlates with increased histone 3 acetylation at the Ifng locus and production of the Th1 cytokine IFN-γ. We find overexpression of GATA-3 restores IL-4 expression in lck−/− Th2 cells; this indicates that the decreased IL-4 expression is due in part to reduced amounts of GATA-3. Taken together, these data imply that Lck mediates Th2 differentiation through effects on T-bet and GATA-3.
Chemokine Receptor 4 Plays a Key Role in T Cell Recruitment into the Airways of Asthmatic Patients
Authors: Vijayanand Pandurangan , Durkin Kesta , Hartmann Guido , Morjaria Jaymin , Seumois Gregory , Staples Karl J. , Hall David , Bessant Christina , Bartholomew Michelle , Howarth Peter H. , Friedmann Peter S. , Djukanović Ratko
Published: March 2010

T lymphocytes of the Th2 type are central orchestrators of airway inflammation in asthma. The mechanisms that regulate their accumulation in the asthmatic airways remains poorly understood. We tested the hypothesis that CCR4, preferentially expressed on T lymphocytes of the Th2 type, plays a critical role in this process. We enumerated by flow cytometry the CCR4-expressing T cells from blood, induced sputum, and biopsy samples of patients with asthma and control subjects. We showed a positive correlation between the numbers of peripheral blood CCR4+ T cells and asthma severity, provided evidence of preferential accumulation of CCR4+ T cells in asthmatic airways, and demonstrated that CCR4+ but not CCR4− cells from patients with asthma produce Th2 cytokines. Explanted airway mucosal biopsy specimens, acquired by bronchoscopy from subjects with asthma, were challenged with allergen and the explant supernatants assayed for T cell chemotactic activity. Allergen-induced ex vivo production of the CCR4 ligand, CCL17 was raised in explants from patients with asthma when compared with healthy controls. Using chemotaxis assays, we showed that the T cell chemotactic activity generated by bronchial explants can be blocked with a selective CCR4 antagonist or by depleting CCR4+ cells from responder cells. These results provide evidence that CCR4 might play a role in allergen-driven Th2 cell accumulation in asthmatic airways. Targeting this chemokine receptor in patients with asthma might reduce Th2 cell-driven airway inflammation; therefore, CCR4 antagonists could be an effective new therapy for asthma. This study also provides wider proof of concept for using tissue explants to study immunomodulatory drugs for asthma.
Disrupting the Intermolecular Self-Association of Itk Enhances T Cell Signaling
Authors: Min Lie , Wu Wenfang , Joseph Raji E. , Fulton D. Bruce , Berg Leslie , Andreotti Amy H.
Published: March 2010

The Tec family tyrosine kinase (Itk), is a key component of the TCR signaling pathway. Biochemical studies have shown that Itk activation requires recruitment of Itk to the membrane via its pleckstrin homology domain, phosphorylation of Itk by the Src kinase, Lck, and binding of Itk to the SLP-76/LAT adapter complex. However, the regulation of Itk enzymatic activity by Itk domain interactions is not yet well understood. In this study, we show that full-length Itk self-associates in an intermolecular fashion. Using this information, we have designed an Itk variant that exhibits reduced self-association but maintains normal binding to exogenous ligands via each of its regulatory domains. When expressed in insect cells, the Itk substrate phospholipase Cγ1 is phosphorylated more efficiently by the Itk variant than by wild-type Itk. Furthermore, expression of the Itk variant in primary murine T cells induced higher ERK activation and increased calcium flux following TCR stimulation compared with that of wild-type Itk. Our results indicate that the Tec kinase Itk is negatively regulated by intermolecular clustering and that disruption of this clustering leads to increased Itk kinase activity following TCR stimulation.
Access to the Spleen Microenvironment through Lymph Shows Local Cytokine Production, Increased Cell Flux, and Altered Signaling of Immune Cells during Lipopolysaccharide-Induced Acute Inflammation
Authors: Semaeva Elvira , Tenstad Olav , Skavland Jørn , Enger Marianne , Iversen Per Ole , Gjertsen Bjørn Tore , Wiig Helge
Published: March 2010

The spleen is involved in fluid volume regulation, immune responses, and hematopoiesis. Yet, the composition of the fluid phase within the spleen microenviroment, the migratory routes of lymphocytes as well as the splenic response to bacterial endotoxin is incomplete. To address these issues, we isolated postnodal lymph in rats by cannulating an efferent lymphatic draining the spleen, and assessed the secretion of signaling substances during a septic response induced by LPS. Spleen lymph flow increased 8-fold after LPS exposure. The spleen exhibited a permeable microvasculature with low sieving of macromolecules that was absent after exposure to LPS. Furthermore, after LPS exposure the spleen contributed significantly to the production of pro- and anti-inflammatory cytokines, and experiments in splenectomized rats suggested it may induce a protracted inflammation because of a dominant role in IL-6 production. A significant amount of lymphocytes exited via lymphatics draining the spleen in control rats. LPS-induced inflammation resulted in increased T cell and reduced B cell subset fractions, and gave a significant increase in CD4+ and CD8+ subset T cell efflux and a reduced B cell efflux in spleen lymph. Exposure of leukocytes to the spleen microenvironment affected their signaling status, and by phosphorylation specific flow cytometry we could identify STAT3 and CREB as important mediators in the cellular signaling occurring during endotoxemia. We conclude that analysis of spleen lymph may unravel immune cell migration patterns and local signaling, and immune cells exit via lymph having acquired specific activation signatures after exposure to the spleen microenvironment.
Lysophosphatidylcholine Increases Neutrophil Bactericidal Activity by Enhancement of Azurophil Granule-Phagosome Fusion via Glycine·GlyRα2/TRPM2/p38 MAPK Signaling
Authors: Hong Chang-Won , Kim Taek-Keun , Ham Hwa-Yong , Nam Ju-Suk , Kim Yong Ho , Zheng Haifeng , Pang Bo , Min Tae-Kwon , Jung Jun-Sub , Lee Si-Nae , Cho Hyun-Jeong , Kim Ee-Jin , Hong In-Hwan , Kang Tae-Cheon , Lee Jongho , Oh Seog Bae , Jung Sung Jun , Kim Sung Joon , Song Dong-Keun
Published: March 2010

Neutrophils are the first-line defense against microbes. Enhancing the microbicidal activity of neutrophils could complement direct antimicrobial therapy for controlling intractable microbial infections. Previously, we reported that lysophosphatidylcholine (LPC), an endogenous lipid, enhances neutrophil bactericidal activity (Yan et al. 2004. Nat. Med. 10: 161–167). In this study we show that LPC enhancement of neutrophil bactericidal activity is dependent on glycine, and is mediated by translocation of intracellularly located glycine receptor (GlyR) α2 to the plasma membrane, and subsequent increase in azurophil granule-phagosome fusion/elastase release. LPC induced GlyRα2-mediated [Cl−]i increase, leading to transient receptor potential melastatin (TRPM)2-mediated Ca2+ influx. Studies using human embryonic kidney 293 cells heterologously expressing TRPM2 and neutrophils showed that TRPM2 channel activity is sensitive to [Cl−]i. Finally, LPC induced p38 MAPK phosphorylation in an extracellular calcium/glycine dependent manner. SB203580, a p38 MAPK inhibitor, blocked LPC-induced enhancement in Lucifer yellow uptake, azurophil granule-phagosome fusion, and bactericidal activity. These results propose that enhancement of azurophil granule-phagosome fusion via GlyRα2/TRPM2/p38 MAPK signaling is a novel target for enhancement of neutrophil bactericidal activity.
Polycomb Group Gene Product Ring1B Regulates Th2-Driven Airway Inflammation through the Inhibition of Bim-Mediated Apoptosis of Effector Th2 Cells in the Lung
Authors: Suzuki Akane , Iwamura Chiaki , Shinoda Kenta , Tumes Damon J. , Y. Kimura Motoko , Hosokawa Hiroyuki , Endo Yusuke , Horiuchi Shu , Tokoyoda Koji , Koseki Haruhiko , Yamashita Masakatsu , Nakayama Toshinori
Published: March 2010

Polycomb group (PcG) gene products regulate the maintenance of homeobox gene expression in Drosophila and vertebrates. In the immune system, PcG molecules control cell cycle progression of thymocytes, Th2 cell differentiation, and the generation of memory CD4 T cells. In this paper, we extended the study of PcG molecules to the regulation of in vivo Th2 responses, especially allergic airway inflammation, by using conditional Ring1B-deficient mice with a CD4 T cell-specific deletion of the Ring1B gene (Ring1B−/− mice). In Ring1B−/− mice, CD4 T cell development appeared to be normal, whereas the differentiation of Th2 cells but not Th1 cells was moderately impaired. In an Ag-induced Th2-driven allergic airway inflammation model, eosinophilic inflammation was attenuated in Ring1B−/− mice. Interestingly, Ring1B−/− effector Th2 cells were highly susceptible to apoptosis in comparison with wild-type effector Th2 cells in vivo and in vitro. The in vitro experiments revealed that the expression of Bim was increased at both the transcriptional and protein levels in Ring1B−/− effector Th2 cells, and the enhanced apoptosis in Ring1B−/− Th2 cells was rescued by the knockdown of Bim but not the other proapoptotic genes, such as Perp, Noxa, or Bax. The enhanced apoptosis detected in the transferred Ring1B−/− Th2 cells in the lung of the recipient mice was also rescued by knockdown of Bim. Therefore, these results indicate that Ring1B plays an important role in Th2-driven allergic airway inflammation through the control of Bim-dependent apoptosis of effector Th2 cells in vivo.
Evaluation of Sub-lethal Toxicity of Cyanobacteria on the Swimming Activity of Aquatic Organisms by Image Analysis
Authors: Ferrão-Filho Aloysio da S. , Cunha R. , Magalhães V. F. , Soares M. C. S. , Baptista D. F.
Published: March 2010

This study evaluated the sub-lethal toxicity of cyanobacteria, especially Cylindrospermosis raciborskii, on Daphnia pulex (water-flea) and Danio rerio (fish), through automated image processing, with the aim to develop a Real-Time Biomonitoring System (RTBS) for detection of toxic cyanobacteria in water supplies. A system composed of a video camera coupled to an image analyzer (Videomex-V®) and to a computer was used to evaluate the swimming activities of D. rerio and D. pulex. The parameters ‘mean distance performed’ and ‘mean velocity’ were used as endpoints to evaluate the effect of samples of cyanobacteria cultures or to raw water from the eutrophic Funil Reservoir. Results showed that both cyanobacteria cultures and water samples from the reservoir altered the swimming activities of D. rerio, elevating the values of mean distance performed and mean velocity. For D. pulex, the cyanobacteria cells caused the opposite effect, decreasing the swimming activity parameters, which can be related to the mechanism of action of saxitoxins. It was concluded that this system can be efficiently used in the detection of toxic blooms of saxitoxin producing cyanobacteria in water supplies.
Comparative Studies of Delthametrin Acute Toxicity in Exotic and Brazilian Fish
Authors: Osti S. C. , Varoli F. M. F. , Matushima E. R. , Bernardi Maria Martha
Published: March 2010

Deltamethrin (2,2-dimetil-3-(2,2-dibromovinil)-ciclopropilcarboxilate alpha-cianofenoxibenzilo), a type II pyrethroid, is used in agricultural applications such as fruits and vegetables plantations, and as maidservants in the combat to fleas, ticks and mange on pets. In the present study, tests of acute toxicity were performed with this pesticide in commercial formulation for the species Danio rerio, Hyphessobricon bifasciatus, Geophagus brasiliensis and Oreochromis niloticus with the objective of determining the values of lethal concentration 50% (LC50), 48h. The tests demonstrated similar toxicity to the pesticide for D. rerio and H. bifasciatus. The values of LC50;48h is 0.078 μg L–1 to D. rerio and 0.082 μg L–1 for H. bifasciatus with 95% confidence limits 0.05-0.11 μL–1 for both. The tests performed with the species G. brasiliensis presented values of LC50;48h of 0.594 μg L–1 with 95% confidence limits 0.33-0.94 μg L–1. The species O. niloticus presented in the tests the largest values of LC50;48h among the used species, 0.954 μg L–1 with 95% confidence limits 0.71-1.22 μg L–1. The tests demonstrated a great toxicity of the pesticide for all tested species of the fishes, demonstrating that the contamination of aquatic environmental can cause great fish slaughter in a short period of time, indicating the require of special attention in relation to its use.
Water Toxicity Assessment of the Ceará River Estuary (Brazil)
Authors: Nilin Jeamylle , Castro C. B. de , Pimentel M. F. , Franklin Júnior W. , Matos R. F. G. de , Lotufo T. M. C. , Costa-Lotufo L. V.
Published: March 2010

The Ceará River Basin is one of the three major water sources of the Metropolitan Region of Fortaleza, Ceará State, Brazil. As an urban river, it receives domestic and industrial effluents, but the impacts of such discharges were not properly investigated. This research focused on the evaluation of the quality of the Ceará river estuary using the sea urchin Lytechinus variegatus embryo-larval toxicity test. Four sampling stations were distributed along the estuary, and the water samples were collected monthly from March 2004 through February 2005. The physical-chemical analyses showed a gradient of salinity and pH from the inner part of the estuary towards the river mouth, while dissolved oxygen (DO) and temperature values were very similar among the stations. Toxicity occurred in three of four surveyed stations, especially at S1 and S2, where the effects were more evident. The higher toxicity at these stations may be related to the proximity to the confluence between Ceará River and Maranguapinho River, which carries effluents from Maracanaú’s Industrial District.
Can the Biomonitor Tillandsia usneoides Be Used to Estimate Occupational and Environmental Mercury Levels in the Air?
Authors: Fonseca Márlon de Freitas , Bastos W. R. , Pinto F. N. , Rebelo M. de F. , Torres J. P. M. , Guimarães J. R. D. , Pfeiffer W. C. , Marques R. G. , Malm O.
Published: March 2010

Spanish moss, the epiphyte bromeliad Tillandsia usneoides (in Brazil, “Barba-de-velho”), has been used as biomonitor to evaluate air pollutants. In this article, total Hg concentrations were determined in bromeliads exposed at different areas of a Brazilian chlor-alkali plant while a calibration curve was built under controlled conditions in order to estimate atmospheric Hg concentrations. Hg determinations were performed by atomic absorption spectrometry. In the laboratory, the bromeliad exhibited linear Hg retention (r = 0.99; p < 0.05) when exposed to different Hg concentrations for 15 days under controlled conditions. While Tillandsia usneoides allows simultaneous and continuous monitoring of several workplaces inside a factory, identifying critical areas where workers can be overexposed, we conclude that bromeliad biomonitoring does not appear to be a trustworthy procedure to estimate Hg concentration in the air. However, this just can be a useful method for identifying and monitoring critical sites in continuous occupational and environmental control risk programs.
Selection of Relevant Effect Levels for Using Bioequivalence Hypothesis Testing
Authors: Bertoletti Eduardo , Buratini S. V. , Prósperi Valéria Aparecida , Araújo R. P. A. , Werner L. I.
Published: March 2010

The use of classic hypotheses tests based on a null hypothesis of equal means frequently promote the occurrence of false positives and false negatives in ecotoxicological assays results. The use of criteria or appropriate statistical analyses is recommended to prevent these occurences and to guarantee the quality of the results from the biological as well statistical point of view. Therefore, the relevant effect levels were established for ecotoxicological assays with Daphnia similis, Ceriodaphnia dubia, Danio rerio, Hyalella azteca, H. meinerti, Lytechinus variegatus and Mysidopsis juniae. Such effect levels were estimated on the basis of the 75th percentile of the Minimum Significant Difference (MSD) of a historical series of analytical results. The estimated values were used to evaluate the allowable variability of the analytical results. It was demonstrated that the integration between the relevant effect levels and the bioequivalence hypothesis testing minimizes the occurrence of false positive results relative to those observed using traditional hypothesis testing.