bluuebunny/crossref_metadata_2025 huggingface dataset:
Louviers - Le Vaudreuil : l'impact spatial d'un pôle d'emploi comme moyen d'évaluation du changement social.
Authors: Guermond Yves
Published: September 2010

Louviers-Le Vaudreuil : spatial impact of an employment centre as a means of evaluation of social change.

The agglomeration of LLV has been favoured till 75 by a regular increase of employment, because of the proximity of Paris. Nevertheless the type of the new industries has been responsible for an increase of unskilled workers and for a poor classification of female employment. More than one worker out of four has arrived in the empolyment centre since 68. These immigrants often have high qualifications, such as the commuters living far from the centre, whereas the recruitment of workmen from the rural milieu remains important in the immediate outskirts.
Socialisation éclatée et conflits dans les grands ensembles Rennais
Authors: Kaufmann Jean-Claude
Published: September 2010

L'article traite des modes d'habiter dans les logements sociaux collectifs. Y sont notamment analysées l'extrême diversité des modèles culturels et les conditions qui expliquent comment cette diversité produit soit l'éclatements de conflits (les principaux motifs de conflits sont répertoriés), soit une socialisation réelle subordonnée à la domination d'une fraction des locataires.
Equipements collectifs et grands ensembles : le cas des centres sociaux
Authors: Laigneau Monique
Published: September 2010

Opérant un classement des familles populaires habitant les grands ensembles en trois groupes, familles précarisées, familles relativement stabilisées, familles appartenant à la nouvelle petite bourgeoisie instruite et salariée, l'article montre la diversité de leurs représentations et de leurs modes d'usage à l'égard des centres sociaux. A partir d'un exemple, celui de la fréquentation des haltes garderies, il essaie de mettre à jour les changements sociaux qui traversent les modèles culturels de ces familles.
Les interruptions volontaires de grossesse en Bretagne : bilan 1976-1979
Authors: Lariviere Jean-Pierre
Published: September 2010

FRE : Démographie, Avortement, Bretagne.
Problèmes climato-océanographiques du désert côtier d'Angola particulièrement la baie des Tigres (16° 35'S)
Authors: Guilcher André
Published: September 2010

A discussion leads to the conclusion that the coastal desert of Southern Angola is really due, as thought before, to a coastal upwelling of cold water, although Portuguese and Russian hydrological surveys off the coast have shown the (occasional ?) presence of a North-South, warm current (the so-called Angola current) and brought complications in the traditional model. It may be that the heavy rains observed sometimes in March at Baia dos Tigres and Mossamedes would be due to a meandering of the warm current, reaching temporarily the coast and suppressing the upwelling.
Les compagnies maritimes européennes face à la crise.
Authors: Marcadon Jacques
Published: September 2010

La crise a précipité la disparition de certains armements européens qui n'ont pas su, à temps, suivre l'évolution technologique ; d'autres, en revanche, en modernisant leur flotte, en l'internationalisant, continuent de prospérer mais cela ne va pas dans les deux cas sans problèmes humains, sans réduction d'effectifs. Tous les types de compagnies sont touchés, les compagnies privées comme les armements où l'Etat est majoritaire, dans les pays d'économie libérale comme dans les pays socialistes.
Eléments pour une étude comparée du climat au nord et au sud de la presqu'île de Brögger (Spitsberg nord-occidental)
Authors: Joly Daniel , Kergomard Claude
Published: September 2010

Durant une période de 27 jours (du 21 Juillet - 16 Août 1981), des observations météorologiques simultanées ont été effectuées dans deux stations situées en versant nord et sud-ouest de la presqu'île de Brögger {Spitsberg nord-occidental) . La station exposée au sud-ouest présente des caractères « océaniques » plus marqués que l'on peut expliquer par les effets de foehn sur les montagnes {600 à 900 m) qui constituent la presqu'île.
Les ports de commerce de l'estuaire de la Charente
Authors: Guillaume Jacques
Published: September 2010

FRE : Région Poitou-Charentes, Transports maritimes, Ports de commerce secondaires
Une traînée fluviatile éocène à galets de chailles et de quartz dans le Perche sarthois ?
Authors: Ward J.-C.
Published: September 2010

FRE : Eocène inférieur, Epandage fluviatile, Géomorphologie
Les conditions d’émergence de la route de l’encens à la fin du IIe millénaire avant notre ère
Authors: Jasmin M.
Published: September 2010

On s’accorde généralement à penser que les relations commerciales entre l’Arabie et le Levant se sont développées à partir du Fer II avec la mise en place d’une route caravanière, dite «route de l’encens». Une série d’indices concordants m’ont conduit à m’interroger sur la date et les modalités de la mise en place de cette route. Les indications actuellement disponibles suggèrent que les origines du commerce caravanier transarabique sont à rechercher à partir des XIIIe-XIIe siècles dans le contexte de la présence égyptienne au sud de la Palestine tandis que l’approvisionnement en encens de l’Égypte avec le pays de Pount cessent subitement et définitivement vers le XIIe siècle. Par ailleurs, les premières utilisations du dromadaire comme animal de bât au Levant remontent, semble-t-il, à la fin du IIe millénaire. Il est tenu pour acquis que l’émergence de la route de l’encens est intimement liée à la domestication du dromadaire. Il a pu cependant s’agir de deux processus distincts pas nécessairement contemporains, ayant connu des trajectoires de développement au départ séparées.
Notes d'Archéologie et d'Architecture Orientales. 11 - Un pont enjambant un canal à Tello ?
Authors: Margueron Jean-Claude
Published: September 2010

A reappraisal of the “enigmatic structure” found at Tello ninety years ago by Henri de Genouillac and André Parrot leads to a new interpretation. Nothing allowed the previous conclusions of a hypogeus, of a temple, of a dam for a storage basin or of a water regulator. Investigating field observations, drawings and photographs (some unpublished until now) give clearly the solution: this structure is a bridge over a channel. Another conclusion is that the ancient situation of this building on the site was erroneous: a slight translation allowed to put this bridge at a topographic convenient place over a wadi (the ancient channel) crossing the site.
Leucothea as Mater Matuta at Colonia Berytus. A note on local mythology in the Levant and the Hellenisation of a Phoenician city
Authors: Kaizer Ted
Published: September 2010

Cet article défend l’idée que Mater Matuta qui, selon une inscription latine de Deir el-Qal’a, reçut un culte sur le territoire de Berytus n’était pas une importation romaine, étrangère dans l’univers religieux de la colonie, mais l’interpretatio romana de Leucothéa, la déesse avec laquelle elle est identifiée dans le monde gréco-romain et qui reçut souvent un culte au Proche-Orient, en particulier en Phénicie à l’époque romaine. Suivant la thèse que la mythologie doit être considérée comme un élément essentiel de la renégociation continuelle de la culture religieuse gréco-romaine, des inscriptions de la ville sont replacées dans le contexte de l’histoire de Leucothéa. Cet exemple peut encourager d’autres chercheurs à observer davantage l’hellénisation de Bérytus au-delà de l’habillage romain.
Identité culturelle et paysage urbain : remarques sur les processus de transformation des rues à portiques dans l’Antiquité tardive
Authors: Saliou Catherine
Published: September 2010

Dans le second tiers du XXe siècle, des observations réalisées à Alep et Lattaquié ont permis à Jean Sauvaget de proposer un schéma d’évolution des rues à portiques des villes antiques du Proche-Orient aboutissant, au terme d’empiétements multiples, à leur métamorphose en souks. La validité de cette séquence descriptive a été mise en évidence par les travaux archéologiques plus récents. Cette évolution est ordinairement traitée comme le symptôme d’une mutation culturelle profonde aboutissant à la désagrégation des cadres spatiaux de la cité hellénistico-romaine. Pourtant, la lecture des sources littéraires et juridiques conduit à voir dans une partie au moins des phénomènes affectant les portiques de rues dans l’Antiquité tardive l’expression de dynamiques internes, à l’oeuvre dans le droit et les représentations normatives du monde romain. Sont ici présentés trois dossiers concernant respectivement Antioche de Syrie au IVe siècle, Constantinople au Ve siècle et l’empire de Justinien. L’utilisation de l’espace du portique fait partie, dès le début de l’Antiquité tardive, des usages normaux de l’espace urbain, régulés et contrôlés par le pouvoir. Une telle possibilité d’occupation de l’espace public a des précédents au Haut Empire et se trouve prise en compte par le droit romain classique. Ces observations conduisent à nuancer les interprétations de la transformation des rues à portiques en termes de rupture. La documentation textuelle met aussi en évidence la diversité des aménagements des portiques et des situations locales. Le détour par les textes montre enfin la nécessité d’une synthèse archéologique précise, qui devrait porter sur l’ensemble du monde romain.
Extramammary Paget Disease: Review of Patients Seen in a Non-Melanoma Skin Cancer Clinic
Authors: Pang J. , Assaad D. , Breen D. , Fialkov J. , Antonyshyn O. , Balogh J. , Tsao M. , Kamra J. , Czarnota G. , Barnes E.A.
Published: September 2010

Extramammary Paget disease (EMPD) is a rare skin disease commonly found in the anogenital region. In this study, we aimed to identify EMPD patients seen in the non-melanoma skin cancer clinic at Odette Cancer Centre and to describe the treatments delivered and outcomes achieved. From 2000 to 2009, 14 patients were seen. Initial treatment recommendations included imiquimod and surgical excision, although half the patients required more than one treatment modality, highlighting the difficulty of achieving complete eradication of this disease.
Hypofractionated Radiotherapy and Adjuvant Chemotherapy Do Not Increase Radiation-Induced Dermatitis in Breast Cancer Patients
Authors: Hijal T. , Al Hamad A.A. , Niazi T. , Sultanem K. , Bahoric B. , Vuong T. , Muanza T.
Published: September 2010

Purpose: Radiation-induced dermatitis is a common side effect of breast irradiation, with hypofractionation being a well-known risk factor. In the context of the widespread adoption of hypofractionated breast radiotherapy, we evaluated the effect of hypofractionated radiotherapy on the incidence of skin toxicity in patients receiving adjuvant chemotherapy. Patients and Methods: We retrospectively reviewed the records of patients with breast cancer treated from 2004 to 2006 at a single institution. Patients undergoing lumpectomy with or without adjuvant chemotherapy followed by hypofractionated radiotherapy consisting of 42.4 Gy in 16 fractions were included in the study. Using cosmetic and skin toxicity scales, all patients were evaluated weekly during treatment and at scheduled follow-up visits with the radiation oncologist. Results: During the study period, 162 patients underwent radiotherapy, and 30% of those (n = 48) received chemotherapy. Radiotherapy boost to the tumour bed was more common in the chemotherapy group [n = 20 (42%)] than in the radiotherapy-alone group [n = 30 (26%)]. We observed no statistically significant difference between the groups with regard to acute skin toxicity of grade 3 or higher (2.1% in the chemotherapy group vs. 4.4% in the radiation-alone group, p = 0.67) or of grades 1–2 toxicity (62.5% vs. 51.7% respectively, p = 0.23). There was also no significant difference in late grade 3 or higher skin toxicity between the groups (2.1% vs. 0% respectively, p = 0.30) or in grades 1–2 toxicity (20.8% vs. 25.5% respectively, p = 0.69). Similarly, excellent or good cosmetic result scores were similar in both groups (p = 0.80). Conclusions: In our single-institution review, we observed no adverse effects of chemotherapy in combination with hypofractionated whole-breast irradiation. Further investigations are necessary to better elucidate the effects of chemotherapy on skin toxicity in the context of hypofractionated irradiation.
Complete Response of Hepatocellular Carcinoma with Sorafenib and 90y Radioembolization
Authors: Chaudhury P.K. , Hassanain M. , Bouteaud J.M. , Alcindor T. , Nudo C.G. , Valenti D. , Cabrera T. , Kavan P. , Feteih I. , Metrakos P.
Published: September 2010

Advanced hepatocellular carcinoma has a dismal prognosis, with a median overall survival of 7.9 months if untreated and of 10.7 months if treated with sorafenib. We present a case of advanced previously unresectable hepatocellular carcinoma in a 49-year-old man that achieved a pathologic complete response and was made amenable to surgery with sorafenib in combination with 90Y radioembolization. The patient’s survival was more than double the median for patients treated with sorafenib alone.
NON-EQUILIBRIUM SELF‐ORGANIZATION OF STEEL‐BRONZE TRIBOSYSTEM ON THE BASIS OF THE ACOUSTIC EMISSION METHOD
Authors: Filonenko Sergay , Stadnichenko Viacheslav
Published: September 2010

Directed copper to steel mass transfer caused by tribochemical activation and heat flow optimisation is researched in this article. It allows the application of selective transfer effect for contact surfaces of tribosystems without clad metal alloy injection into the lubricant environment. Santrauka Darbe pateiktas kryptiniu vario mases mainu tyrimas, kai varis perne šamas link plieno ne tik del tribocheminio aktyvinimo, bet ir del šilumos srauto oprtimizavimo. Tai leidžia pritaikyti “rinktiniu mainu” efekta nepanardinant tribosistemos kontakto paviršiaus medžiagos i aliejiniu mišiniu, skirtu metalo padengimui, terpe.
Effectiveness of Ketorolac Tromethamine in Prevention of Severe Retinopathy of Prematurity
Authors: Giannantonio Carmen , Papacci Patrizia , Purcaro Velia , Cota Francesco , Tesfagabir Mikael Ghennet , Molle Fernando , Lepore Domenico , Baldascino Antonio , Romagnoli Costantino
Published: September 2010

Purpose:

This study assessed the effectiveness of the use of ketorolac tromethamine to reduce retinopathy of prematurity (ROP) incidence and its progression to more severe forms.

Methods:

Forty-seven preterm newborn infants with a birth weight (BW) of 1,000 grams or less and/or a gestational age (GA) of 29 weeks or less were enrolled in the study when avascular retina zone I or ROP any stage were diagnosed at screening. Studied infants were randomized to receive ketorolac tromethamine ophthalmic solution in one eye and a drop of placebo in the other eye, until ROP requiring treatment or full retinal vascularization was diagnosed.

Results:

Only 2 newborn infants did not develop ROP. Among 45 newborn infants who developed ROP, 6 showed different ROP staging between the two eyes, 4 of which had a better outcome in the eye receiving ketorolac tromethamine. The differences between ROP stagings were not significant even when analyzed by GA and BW subgroups. No significant treatment-related side effects occurred.

Conclusion:

This report suggests that ketorolac tromethamine ophthalmic solution cannot reduce the risk of developing severe ROP in preterm infants.
Clinical Characteristics and Early Postoperative Outcomes of Pediatric Cataract Surgery With IOL Implantation From Lahan, Nepal
Authors: Wilson M. Edward , Hennig Albrecht , Trivedi Rupal H. , Thomas Benjamin J. , Singh Sanjay Kumar
Published: September 2010

Purpose:

To report clinical characteristics and early postoperative outcomes of pediatric cataract surgery with intraocular lens (IOL) implantation from Lahan, Nepal.

Methods:

Demographics and surgical, preoperative, and postoperative clinical characteristics data were collected and analyzed.

Results:

Of 2,633 eyes with primary IOL implantation, 2,003 eyes were in the non-traumatic group, whereas 630 eyes were from trauma. Median age at surgery was 7 and 9 years in the non-traumatic and traumatic groups, respectively. Boys comprised 74.2% of the non-traumatic and 85.4% of the traumatic cataract patients. Unilateral cataracts accounted for only 7.7% (154 of 2,003) of the non-traumatic group. Average follow-up was 35 days with greater than 6 months follow-up in 134 of 2,633 (5.1%) eyes. Most (68.5% [1,804 of 2,633]) of the lens opacities were described as total cataract. Although early postoperative best-corrected visual acuity improved from the preoperative recording in 95.0% (2,495 of 2,626) of eyes, 78.1% (2,050 of 2,626) remained in the poor (20/100 or worse) category. Median preoperative and early postoperative best-corrected visual acuity was hand motions and 20/200, respectively.

Conclusion:

A high-volume cataract surgical center in Lahan, Nepal, is able to provide cost-effective and high-quality pediatric surgery. Most of the patients in this series were noted to have complete cataracts and were boys. Visual improvement was achieved, but excellent visual outcomes were rarely documented due to late referral and inadequate follow-up. Educating families and primary caregivers with regard to the importance of earlier referral and postoperative optical correction and tracking will improve outcomes.
Bilateral Massive Posterior Embryotoxon
Authors: Manusow Joshua S. , Brownstein Seymour , Belliveau Michel J.
Published: September 2010

A 10-week-old infant died suddenly and unexpectedly. Histopathologic examination of the globes showed no signs of trauma but did disclose incidental bilateral, extremely prominent Schwalbe's rings (posterior embryotoxon). The authors believe this case is the largest example of posterior embryotoxon ever published and present a brief review of its associated syndromes.
[J Pediatr Ophthalmol Strabismus 2010;47:e1–e3.]
The Use of the QuantiFERON-Tuberculosis Gold Test in the Diagnosis of Ocular Tuberculosis
Authors: Ozdamar Yasemin , Ozkan Seyhan S. , Beyazyildiz Emrullah , Ozdal Pinar Cakar , Teberik Kuddusi , Altintas Aysegul Kocak
Published: September 2010

Ocular tuberculosis without systemic manifestations may rarely occur. The diagnosis of ocular tuberculosis is important because it has a wide spectrum of presentations and requires a multidisciplinary approach. The QuantiFERON-tuberculosis gold test is a new diagnostic test that may be useful in making a suitable diagnosis.
[J Pediatr Ophthalmol Strabismus 2010;47:e1–e3.]
The Importance of Exercise for Individuals with Chronic Mental Illness
Authors: Weber Mary
Published: September 2010

This article reviews the use of exercise as a therapeutic and adjunctive intervention in the prevention of weight gain, obesity, and metabolic consequences in multiple populations with psychiatric illnesses. The purpose was to identify the current state of the science for the use of exercise as a psychiatric nursing intervention, as well as the gaps and methodological issues in current studies. To do this, research and review articles published between 1998 and 2010 were reviewed. It was found that psychiatric nurses are taking the first steps in incorporating exercise into their recommendations and interventions in populations with psychiatric illnesses, but a long journey remains to make a significant difference in clients’ lives.
Use of Animal-Assisted Therapy with Psychiatric Patients
Authors: Rossetti Jeanette , King Camille
Published: September 2010

The use of animal-assisted therapy (AAT) as an adjunct treatment approach in psychiatric settings has received much attention in the literature. This article explores the use of AAT with psychiatric patients. The authors performed a literature review and found that AAT can have a significant effect on the improvement of psychiatric patients’ socialization and provides a variety of psychological benefits. Nurses can benefit from learning about the potential benefits of AAT for psychiatric patients.
Serendipity and Psychopharmacology
Authors: Howland Robert H.
Published: September 2010

This article describes several examples where the development of drugs and devices for use in psychiatry followed from initial serendipitous observations. The potential psychotropic properties of chlorpromazine (Thorazine
®
) were first noted in surgical patients when the drug was being investigated as a potentiator of anesthesia. Similar findings were noted with iproniazid (Marsilid
®
), developed for the treatment of tuberculosis, and the drug was later released for clinical use as an antidepressant agent. The development of meprobamate (Miltown
®
), an approved treatment for anxiety, evolved from initial efforts to find a chemical that would inhibit the enzymatic destruction of the antibiotic drug penicillin. The psychiatric uses of lamotrigine (Lamictal
®
) and vagus nerve stimulation were prompted by initial observations that epilepsy patients receiving these treatments had positive mood effects. Nurses should be familiar with the concept of serendipity, as they often are in the best position to observe, record, and report on unexpected clinical effects in patients taking any kind of prescription or nonprescription medication.
Behavioral Symptoms of Dementia: A Dyadic Effect of Caregivers’ Stress Process?
Authors: Campbell Judy L.M. , Rowe Meredeth A. , Marsiske Michael
Published: September 2010

This study used multilevel modeling to evaluate a newly revised model in which dementia caregivers’ stress process variables—perceived stress and emotional-behavioral responses—were posited as predictors of behavioral symptoms of dementia (BSD) within community-based dyads. Secondary analyses were conducted on data from a primary two-group (experimental and control) trial, in which experimental participants received a home monitoring system for managing nighttime activity in individuals with dementia. Models indicated that caregivers’ trajectories did not differ significantly between groups over time; however, the time-by-group interaction of BSD approached significance. Because BSD were not targeted, this indicated that the system may have indirectly lowered BSD. In addition, caregivers’ perceived stress and emotional-behavioral responses predicted BSD, on average (across all occasions) and from occasion to occasion, with higher levels associated with worse BSD. These limited results provide support for further research to investigate the nature of these relationships.
Culturally Determined Preferences
Authors: Stewart Osamuyimen , Chakraborty Joyram
Published: September 2010

Theoretical models for the study of cross cultural variables in communication abound. However, there are very few empirical studies to validate any of these models in the Human-Computer Interaction (HCI) literature involving Automatic Speech Recognition (ASR). This is the gap this chapter seeks to fill by addressing the broad and foundational question of whether a framework for cross cultural dimensions can be used to investigate how people use (or are likely to use) ASR systems versus Live (human) help. In particular, the authors focus on one of Hofstede’s (1991) five factors: individualism-collectivism. They show that using Hofstede’s questionnaire does not yield expected results in the HCI domain involving ASR. Consequently, the authors propose a new set of questions derived from cultural and psycholinguistic factors surrounding how people might tackle some common problems. This new questionnaire proves to be effective in deriving the cross-cultural distinctions congruent with benchmarked predictions, while also providing empirical evidence for culturally determined preferences for the use of ASR systems. Furthermore, the authors explore one implication from this study based on the discussion of the cross-cultural correlation between the nature of a task (simple or complex) and the evolution or adoption of ASR systems for self help.
Developing Enculturated Agents
Authors: Rehm Matthias
Published: September 2010

Embodied Conversational Agents (ECAs) are complex multimodal systems with rich verbal and nonverbal repertoires. There human-like appearance raises severe expectations regarding natural communicative behaviors on the side of the user. But what is regarded as “natural” is to a large degree dependent on our cultural profiles that provide us with heuristics of behavior and interpretation. Thus, integrating cultural aspects of communicative behaviors in virtual agents and thus enculturating such systems seems to be inevitable. But culture is a multi-defined domain and thus a number of pitfalls arise that have to be avoided in the endeavor. This chapter presents some of the pitfalls for enculturating interactive systems and presents strategies on how to avoid these pitfalls in relation to the standard development process of Embodied Conversational Agents.
Blending Educational Models to Design Blended Activities
Authors: Ligorio M. Beatrice , Loperfido F. Feldia , Sansone Nadia , Spadaro Paola F.
Published: September 2010

The authors claim that the potentialities of the socio-constructivist framework can be fully exploited when a blended approach is introduced. Our blended model does not only mix offline and online contexts but it also combines several pedagogical theories and techniques (Progressive Inquiry Model, Jigsaw, Reciprocal Teaching, Collaborative Communities, and Dialogical Knowledge). The particular mix the authors propose generates a specific pedagogy through which a set of blended activities is designed. Some analyses conducted on blended courses for higher education and professional development where blended activities were tested are briefly discussed. These analyses concern: (a) the students’ participation in blended context, (b) their expectations about the blended course and their perception about the processes of collaborative knowledge building, (c) the impact on students of role-taking, which is one of the blended activities included into the blended course. Results show that our blended approach has an impact on how students interact and talk in groups. At the end of the course, students display a collaborative discourse strategy mainly based on: (a) completing each other’s sentence, (b) complex trajectories of participation, (c) changes of the perception of the self and of the group and (d) the effects of role-playing.
Considerations for Effective Collaborative Practice
Authors: McGhie-Richmond Donna , Winter Eileen
Published: September 2010

This chapter provides a retrospective review of the utility and effectiveness of case study analyses to engage and support students in online collaborative learning within teacher education coursework. Specifically, the interrelationship among factors related to the instructor, the student, the tasks, and the on-line learning environments are examined resulting in suggestions for designing, implementing, and researching case study learning activities that foster and enhance collaboration in online teacher education course work.
Using Role Play and Team Teaching as Strategies to Add Depth to Online Discussion
Authors: Lombard Ron , Biglan Barbara
Published: September 2010

This is a review of an action research project dealing with the impact of a role playing activity in an online course. Two instructors of an online graduate course collected observable data based on response and participation levels of students in an online discussion setting. Subsequently, utilizing the same discussion topic, the instructors combined for a course delivery team teaching and role playing approach to the discussion. In the second course the instructors assumed the roles of John Dewey, Mao Tse-Tung, and Aristotle and exchanged responses and comments with each other and with students. A comparison of the levels of responses between the two approaches utilizing the same rubric allowed to measure the impact of role play and team teaching. A review of research related to team teaching and role playing as approaches to enhance discussions provides background to decision to utilize these two approaches to enhance the discussion process.
Heparan Sulfate, Including That in Bruch’s Membrane, Inhibits the Complement Alternative Pathway: Implications for Age-Related Macular Degeneration
Authors: Kelly Una , Yu Ling , Kumar Pallavi , Ding Jin-Dong , Jiang Haixiang , Hageman Gregory S. , Arshavsky Vadim Y. , Frank Michael M. , Hauser Michael A. , Bowes Rickman Catherine
Published: September 2010

An imbalance between activation and inhibition of the complement system has been implicated in the etiologies of numerous common diseases. Allotypic variants of a key complement fluid-phase regulatory protein, complement factor H (CFH), are strongly associated with age-related macular degeneration (AMD), a leading cause of worldwide visual dysfunction, although its specific role in AMD pathogenesis is still not clear. CFH was isolated from individuals carrying combinations of two of the nonsynonymous coding variants most strongly associated with AMD risk, V62/H402 (risk haplotype variants), I62/Y402 (nonrisk haplotype variants), and V62/Y402. These proteins were used in two functional assays (cell surface- and fluid-phase–based) measuring cofactor activity of CFH in the factor I-mediated cleavage of C3b. Although no variant-specific differences in the cofactor activity were detected, when heparan sulfate (HS) was added to these assays, it accelerated the rate of C3b cleavage, and this effect could be modulated by degree of HS sulfation. Bruch’s membrane/choroid, a site of tissue damage in AMD, contains high concentrations of glycosaminoglycans, including HS. Addition of human Bruch’s membrane/choroid to the fluid-phase assay accelerated the C3b cleavage, and this effect was lost posttreatment of the tissue with heparinase III. Binding of CFH variants to Bruch’s membrane/choroid isolated from elderly, non-AMD donor eyes, was similar, as was the functional activity of bound CFH. These findings refine our understanding of interactions of HS and complement and support the hypothesis that these interactions play a role in the transition between normal aging and AMD in Bruch’s membrane/choroid.
Adjuvant Immunotherapy Increases β Cell Regenerative Factor Reg2 in the Pancreas of Diabetic Mice
Authors: Huszarik Katrina , Wright Benjamin , Keller Christina , Nikoopour Enayat , Krougly Olga , Lee-Chan Edwin , Qin Hui-Yu , Cameron Mark J. , Gurr Werner K. , Hill David J. , Sherwin Robert S. , Kelvin David J. , Singh Bhagirath
Published: September 2010

Insulin-producing β cells can partially regenerate in adult pancreatic tissues, both in human and animal models of type 1 diabetes (T1D). Previous studies have shown that treatment with mycobacterial adjuvants such as CFA and bacillus Calmette-Guérin prevents induction and recurrence of T1D in NOD mice with partial recovery of β cell mass. In this study, we investigated factors involved in the regeneration of β cells in the pancreas of NOD mice during diabetes development and after treatment with adjuvants. The Regeneration (Reg) gene family is known to be involved in regeneration of various tissues including β cells. Reg2 expression was found to be upregulated in pancreatic islets both during diabetes development and as a result of adjuvant treatment in diabetic NOD mice and in C57BL/6 mice made diabetic by streptozotocin treatment. The upregulation of Reg2 by adjuvant treatment was independent of signaling through MyD88 and IL-6 because it was not altered in MyD88 or IL-6 knockout mice. We also observed upregulation of Reg2 in the pancreas of diabetic mice undergoing β cell regenerative therapy with exendin-4 or with islet neogenesis-associated protein. Reg2 expression following adjuvant treatment correlated with a reduction in insulitis, an increase in insulin secretion, and an increase in the number of small islets in the pancreas of diabetic NOD mice and with improved glucose tolerance tests in streptozotocin-treated diabetic C57BL/6 mice. In conclusion, adjuvant immunotherapy regulates T1D in diabetic mice and induces Reg2-mediated regeneration of β cells.
Enhanced Antiviral T Cell Function in the Absence of B7-H1 Is Insufficient To Prevent Persistence but Exacerbates Axonal Bystander Damage during Viral Encephalomyelitis
Authors: Phares Timothy W. , Stohlman Stephen A. , Hinton David R. , Atkinson Roscoe , Bergmann Cornelia C.
Published: September 2010

The T cell inhibitory ligand B7-H1 hinders T cell-mediated virus control, but also ameliorates clinical disease during autoimmune and virus-induced CNS disease. In mice infected with gliatropic demyelinating coronavirus, B7-H1 expression on oligodendroglia delays virus control, but also dampens clinical disease. To define the mechanisms by which B7-H1 alters pathogenic outcome, virus-infected B7-H1–deficient (B7-H1−/−) mice were analyzed for altered peripheral and CNS immune responses. B7-H1 deficiency did not affect peripheral T or B cell activation or alter the magnitude or composition of CNS-infiltrating cells. However, higher levels of IFN-γ mRNA in CNS-infiltrating virus-specific CD8 T cells as well as CD4 T cells contributed to elevated IFN-γ protein in the B7-H1−/− CNS. Increased effector function at the single-cell level was also evident by elevated granzyme B expression specifically in virus-specific CNS CD8 T cells. Although enhanced T cell activity accelerated virus control, 50% of mice succumbed to infection. Despite enhanced clinical recovery, surviving B7-H1−/− mice still harbored persisting viral mRNA, albeit at reduced levels compared with wild-type mice. B7-H1−/− mice exhibited extensive loss of axonal integrity, although demyelination, a hallmark of virus-induced tissue damage, was not increased. The results suggest that B7-H1 hinders viral control in B7-H1 expressing glia cells, but does not mediate resistance to CD8 T cell-mediated cytolysis. These data are the first, to our knowledge, to demonstrate that B7-H1–mediated protection from viral-induced immune pathology associated with encephalomyelitis resides in limiting T cell-mediated axonal bystander damage rather than direct elimination of infected myelinating cells.
Effects of SR141716A on Cognitive and Depression-Related Behavior in an Animal Model of Premotor Parkinson's Disease
Authors: Tadaiesky M. T. , Dombrowski P. A. , Da Cunha C. , Takahashi R. N.
Published: September 2010

A previous study from our laboratory revealed that moderate nigral dopaminergic degeneration caused emotional and cognitive deficits in rats, paralleling early signs of Parkinson's disease. Recent evidence suggests that the blockade of cannabinoid CB1receptors might be beneficial to alleviate motor inhibition typical of Parkinson's disease. Here, we investigated whether antagonism of CB1receptors would improve emotional and cognitive deficits in a rat model of premotor Parkinson's disease. Depression-like behavior and cognition were assessed with the forced swim test and the social recognition test, respectively. Confirming our previous study, rats injected with 6-hydroxydopamine in striatum presented emotional and cognitive alterations which were improved by acute injection of SR141716A. HPLC analysis of monoamine levels demonstrated alterations in the striatum and prefrontal cortex after SR141716A injection. These findings suggest a role for CB1receptors in the early symptoms caused by degeneration of dopaminergic neurons in the striatum, as observed in Parkinson's disease.
Patent Medicine Sellers: How Can They Help Control Childhood Malaria?
Authors: Akuse Rosamund M. , Eseigbe Edwin E. , Ahmed Abubakar , Brieger William R.
Published: September 2010

Roll Back Malaria Initiative encourages participation of private health providers in malaria control because mothers seek care for sick children from them. This study investigated Patent Medicine Sellers (PMS) management of presumptive malaria in children in order to identify how they can assist malaria control. A cross-sectional survey of 491 PMS in Kaduna, Nigeria, was done using interviews and observation of shop activities. Most (80%) customers bought drugs without prescriptions. Only 29.5% were given instructions about doses. Between 40–100% doses of recommended antimalarials were incorrect. Some (22%) PMS did not ask questions about illness for which they were consulted. Most children treated in shops received injections. PMS facilitate homecare but have deficiencies in knowledge and practice. Interventions must focus on training them to accurately determine doses, give advice about drug administration, use oral medication, and ask about illness. Training should be made a prerequisite for registering and reregistering shops.
Error‐Prone Translesion DNA Synthesis byEscherichia coli DNA Polymerase IV (DinB) on Templates Containing 1,2‐dihydro‐2‐oxoadenine
Authors: Hori Masaki , Yonekura Shin-Ichiro , Nohmi Takehiko , Gruz Petr , Sugiyama Hiroshi , Yonei Shuji , Zhang-Akiyama Qiu-Mei
Published: September 2010

Escherichia coli DNA polymerase IV (Pol IV) is involved in bypass replication of damaged bases in DNA. Reactive oxygen species (ROS) are generated continuously during normal metabolism and as a result of exogenous stress such as ionizing radiation. ROS induce various kinds of base damage in DNA. It is important to examine whether Pol IV is able to bypass oxidatively damaged bases. In this study, recombinant Pol IV was incubated with oligonucleotides containing thymine glycol (dTg), 5‐formyluracil (5‐fodU), 5‐hydroxymethyluracil (5‐hmdU), 7,8‐dihydro‐8‐oxoguanine (8‐oxodG) and 1,2‐dihydro‐2‐oxoadenine (2‐oxodA). Primer extension assays revealed that Pol IV preferred to insert dATP opposite 5‐fodU and 5‐hmdU, while it inefficiently inserted nucleotides opposite dTg. Pol IV inserted dCTP and dATP opposite 8‐oxodG, while the ability was low. It inserted dCTP more effectively than dTTP opposite 2‐oxodA. Pol IV′s ability to bypass these lesions decreased in the order: 2‐oxodA > 5‐fodU~5‐hmdU > 8‐oxodG > dTg. The fact that Pol IV preferred to insert dCTP opposite 2‐oxodA suggests the mutagenic potential of 2‐oxodA leading to A:T→G:C transitions. Hydrogen peroxide caused an ~2‐fold increase in A:T→G:C mutations in E. coli, while the increase was significantly greater in E. coli overexpressing Pol IV. These results indicate that Pol IV may be involved in ROS‐enhanced A:T→G:C mutations.
Mechanistic Studies with DNA Polymerases Reveal Complex Outcomes following Bypass of DNA Damage
Authors: Eoff Robert L. , Choi Jeong-Yun , Guengerich F. Peter
Published: September 2010

DNA is a chemically reactive molecule that is subject to many different covalent modifications from sources that are both endogenous and exogenous in origin. The inherent instability of DNA is a major obstacle to genomic maintenance and contributes in varying degrees to cellular dysfunction and disease in multi‐cellular organisms. Investigations into the chemical and biological aspects of DNA damage have identified multi‐tiered and overlapping cellular systems that have evolved as a means of stabilizing the genome. One of these pathways supports DNA replication events by in a sense adopting the mantra that one must “make the best of a bad situation” and tolerating covalent modification to DNA through less accurate copying of the damaged region. Part of this so‐called DNA damage tolerance pathway involves the recruitment of specialized DNA polymerases to sites of stalled or collapsed replication forks. These enzymes have unique structural and functional attributes that often allow bypass of adducted template DNA and successful completion of genomic replication. What follows is a selective description of the salient structural features and bypass properties of specialized DNA polymerases with an emphasis on Y‐family members.
Elevated Levels of DNA Strand Breaks Induced by a Base Analog in the Human Cell Line with the P32T ITPA Variant
Authors: Waisertreiger Irina S.-R. , Menezes Miriam R. , Randazzo James , Pavlov Youri I.
Published: September 2010

Base analogs are powerful antimetabolites and dangerous mutagens generated endogenously by oxidative stress, inflammation, and aberrant nucleotide biosynthesis. Human inosine triphosphate pyrophosphatase (ITPA) hydrolyzes triphosphates of noncanonical purine bases (i.e., ITP, dITP, XTP, dXTP, or their mimic: 6‐hydroxyaminopurine (HAP) deoxynucleoside triphosphate) and thus regulates nucleotide pools and protects cells from DNA damage. We demonstrate that the model purine base analog HAP induces DNA breaks in human cells and leads to elevation of levels of ITPA. A human polymorphic allele of the ITPA, 94C‐>A encodes for the enzyme with a P32T amino‐acid change and leads to accumulation of nonhydrolyzed ITP. The polymorphism has been associated with adverse reaction to purine base‐analog drugs. The level of both spontaneous and HAP‐induced DNA breaks is elevated in the cell line with the ITPA P32T variant. The results suggested that human ITPA plays a pivotal role in the protection of DNA from noncanonical purine base analogs.
The Use of Endophytes to Obtain Bioactive Compounds and Their Application in Biotransformation Process
Authors: Pimentel Mariana Recco , Molina Gustavo , Dionísio Ana Paula , Maróstica Junior Mário Roberto , Pastore Gláucia Maria
Published: September 2010

Endophytes are microorganisms that reside asymptomatically in the tissues of higher plants and are a promising source of novel organic natural metabolites exhibiting a variety of biological activities. The laboratory of Bioaromas (Unicamp, Brazil) develops research in biotransformation processes and functional evaluation of natural products. With the intent to provide subsidies for studies on endophytic microbes related to areas cited before, this paper focuses particularly on the role of endophytes on the production of anticancer, antimicrobial, and antioxidant compounds and includes examples that illustrate their potential for human use. It also describes biotransformation as an auspicious method to obtain novel bioactive compounds from microbes. Biotransformation allows the production of regio- and stereoselective compounds under mild conditions that can be labeled as “natural,” as discussed in this paper.
Hoofstuk 5 - Politieke spanning en ekumeniese druk 1954–1960
Authors: Oberholzer J.P.
Published: September 2010

Die vak Bybelkunde maak sy verskyning. Die emeritaat van Gemser, S.P. Engelbrecht en H.P. Wolmarans en die toetrede van E.S. Mulder, A.D. Pont en F.J. van Zyl tot Afdeling A bring ‘n radikale verandering. Ekumeniese druk begin oplaai rondom die landspolitiek. Die Cottesloe-konferensie bring beroering. Die houding van A.S. Geyser en A. van Selms wek weerstand.
Hoofstuk 9 - Rasionalisasie en Optimalisering 1988–1997
Authors: Oberholzer J.P.
Published: September 2010

Ontwikkelings op onderwysgebied en finansiële druk bring streng eise en lei tot ‘n intensiewe herstruktureing oor die hele spektrum. Personeelvermindering, hervorming van onderrigmetodes en die eis van uitnemendheid intensifiseer die akademiese bedryf.
Micelle Enhanced Fluorimetric and Thin Layer Chromatography Densitometric Methods for the Determination of (±) Citalopram and its S - Enantiomer Escitalopram
Authors: Taha Elham A. , Salama Nahla N. , Wang Shudong
Published: September 2010

Two sensitive and validated methods were developed for determination of a racemic mixture citalopram and its enantiomer s-(+)escitalopram. The first method was based on direct measurement of the intrinsic fluorescence of escitalopram using sodium dodecyl sulfate as micelle enhancer. This was further applied to determine escitalopram in spiked human plasma, as well as in the presence of common and co-administerated drugs. The second method was TLC densitometric based on various chiral selectors was investigated. The optimum TLC conditions were found to be sensitive and selective for identification and quantitative determination of enantiomeric purity of escitalopram in drug substance and drug products. The method can be useful to investigate adulteration of pure isomer with the cheap racemic form.
Quantitative Mass Spectrometric Analysis of Ropivacaine and Bupivacaine in Authentic, Pharmaceutical and Spiked Human Plasma without Chromatographic Separation
Authors: Salama Nahla N. , Wang Shudong
Published: September 2010

The present study employs time of flight mass spectrometry for quantitative analysis of the local anesthetic drugs ropivacaine and bupivacaine in authentic, pharmaceutical and spiked human plasma as well as in the presence of their impurities 2,6-dimethylaniline and alkaline degradation product. The method is based on time of flight electron spray ionization mass spectrometry technique without preliminary chromatographic separation and makes use of bupivacaine as internal standard for ropivacaine, which is used as internal standard for bupivacaine. A linear relationship between drug concentrations and the peak intensity ratio of ions of the analyzed substances is established. The method is linear from 23.8 to 2380.0 ng mL−1for both drugs. The correlation coefficient was ≥0.996 in authentic and spiked human plasma. The average percentage recoveries in the ranges of 95.39%-102.75% was obtained. The method is accurate (% RE <; 5%) and reproducible with intra- and inter-assay precision (RSD% <; 8.0%). The quantification limit is 23.8 ng mL−1for both drugs. The method is not only highly sensitive and selective, but also simple and effective for determination or identification of both drugs in authentic and biological fluids. The method can be applied in purity testing, quality control and stability monitoring for the studied drugs.
Liquid Chromatography with Post-Column Reagent Addition of Ammonia in Methanol Coupled to Negative Ion Electrospray Ionization Tandem Mass Spectrometry for Determination of Phenoxyacid Herbicides and their Degradation Products in Surface Water
Authors: Raina Renata , Etter Michele L.
Published: September 2010

A new liquid chromatography (LC)-negative ion electrospray ionization (ESI−)–tandem mass spectrometry (MS/MS) method with post-column addition of ammonia in methanol has been developed for the analysis of acid herbicides: 2,4-dichlorophenoxy acetic acid, 4-chloro-o-tolyloxyacetic acid, 2-(2-methyl-4-chlorophenoxy)butyric acid, mecoprop, dichlorprop, 4-(2,4-dichlorophenoxy) butyric acid, 2,4,5-trichlorophenoxy propionic acid, dicamba and bromoxynil, along with their degradation products: 4-chloro-2-methylphenol, 2,4-dichlorophenol, 2,4,5-trichlorophenol and 3,5-dibromo-4-hydroxybenzoic acid. The samples were extracted from the surface water matrix using solid-phase extraction (SPE) with a polymeric sorbent and analyzed with LC ESI−with selected reaction monitoring (SRM) using a three-point confirmation approach. Chromatography was performed on a Zorbax Eclipse XDB-C18 (50 × 4.6 mm i.d., 1.8 μm) with a gradient elution using water-methanol with 2 mM ammonium acetate mobile phase at a flow rate of 0.15 mL/min. Ammonia in methanol (0.8 M) was added post-column at a flow rate of 0.05 mL/min to enhance ionization of the degradation products in the MS source. One SRM transition was used for quantitative analysis while the second SRM along with the ratio of SRM1/SRM2 within the relative standard deviation determined by standards for each individual pesticide and retention time match were used for confirmation. The standard deviation of ratio of SRM1/SRM2 obtained from standards run on the day of analysis for different phenoxyacid herbicides ranged from 3.9 to 18.5%. Limits of detection (LOD) were between 1 and 15 ng L−1and method detection limits (MDL) with strict criteria requiring <25% deviation of peak area from best-fit line for both SRM1 and SRM2 ranged from 5 to 10 ng L−1for acid ingredients (except dicamba at 30 ng L−1) and from 2 to 30 ng L−1for degradation products. The SPE-LC-ESI−MS/MS method permitted low nanogram-per-liter determination of pesticides and degradation products for surface water samples.