bluuebunny/crossref_metadata_2025 huggingface dataset:
Adipocyte-Derived Soluble Factor(s) Inhibits Early Stages of B Lymphopoiesis
Authors: Bilwani Fareena A. , Knight Katherine L.
Published: September 2012

B lymphopoiesis declines with age, and in rabbits this occurs by 8 wk of age. We found that CFU fibroblasts (CFU-Fs) in the bone marrow (BM) decrease 10-fold by a few weeks of age and that the CFU-Fs preferentially differentiate into adipocytes instead of osteoblasts. BM becomes filled with fat spaces during this time, making rabbit a unique model to study the effects of accelerated fat accumulation on B lymphopoiesis. We show that adipocytes of both rabbit and human secrete a soluble factor(s) that inhibits B lymphopoiesis, and we tested if this inhibition was due to effects on the BM stroma or hematopoietic progenitors. Pretreatment of BM mononuclear cells with adipocyte conditioned medium dramatically inhibited their differentiation into proB cells in cocultures with OP9 stromal cells. In contrast, pretreatment of OP9 stromal cells with adipocyte conditioned medium had no effect on B lymphopoiesis. Using human hematopoietic stem cells, we show that inhibition by the adipocyte-derived factor occurred at the common lymphoid progenitor to preproB cell stage. We propose that the age-related decline in B lymphopoiesis is due to a decrease in CFU-Fs, an increase in adipocytes, and an adipocyte-derived factor that blocks B lymphopoiesis at the common lymphoid progenitor to preproB cell stage.
Exposure to Ionizing Radiation Induces the Migration of Cutaneous Dendritic Cells by a CCR7-Dependent Mechanism
Authors: Cummings Ryan J. , Gerber Scott A. , Judge Jennifer L. , Ryan Julie L. , Pentland Alice P. , Lord Edith M.
Published: September 2012

In the event of a deliberate or accidental radiological emergency, the skin would likely receive substantial ionizing radiation (IR) poisoning, which could negatively impact cellular proliferation, communication, and immune regulation within the cutaneous microenvironment. Indeed, as we have previously shown, local IR exposure to the murine ear causes a reduction of two types of cutaneous dendritic cells (cDC), including interstitial dendritic cells of the dermis and Langerhans cells of the epidermis, in a dose- and time-dependent manner. These APCs are critical regulators of skin homeostasis, immunosurveillance, and the induction of T and B cell-mediated immunity, as previously demonstrated using conditional cDC knockout mice. To mimic a radiological emergency, we developed a murine model of sublethal total body irradiation (TBI). Our data would suggest that TBI results in the reduction of cDC from the murine ear that was not due to a systemic response to IR, as a loss was not observed in shielded ears. We further determined that this reduction was due, in part, to the upregulation of the chemoattractant CCL21 on lymphatic vessels as well as CCR7 expressed on cDC. Migration as a potential mechanism was confirmed using CCR7−/− mice in which cDC were not depleted following TBI. Finally, we demonstrated that the loss of cDC following TBI results in an impaired contact hypersensitivity response to hapten by using a modified contact hypersensitivity protocol. Taken together, these data suggest that IR exposure may result in diminished immunosurveillance in the skin, which could render the host more susceptible to pathogens.
Genetic Depletion of Complement Receptors CD21/35 Prevents Terminal Prion Disease in a Mouse Model of Chronic Wasting Disease
Authors: Michel Brady , Ferguson Adam , Johnson Theodore , Bender Heather , Meyerett-Reid Crystal , Pulford Bruce , von Teichman Adriana , Seelig Davis , Weis John H. , Telling Glenn C. , Aguzzi Adriano , Zabel Mark D.
Published: September 2012

The complement system has been shown to facilitate peripheral prion pathogenesis. Mice lacking complement receptors CD21/35 partially resist terminal prion disease when infected i.p. with mouse-adapted scrapie prions. Chronic wasting disease (CWD) is an emerging prion disease of captive and free-ranging cervid populations that, similar to scrapie, has been shown to involve the immune system, which probably contributes to their relatively facile horizontal and environmental transmission. In this study, we show that mice overexpressing the cervid prion protein and susceptible to CWD (Tg(cerPrP)5037 mice) but lack CD21/35 expression completely resist clinical CWD upon peripheral infection. CD21/35-deficient Tg5037 mice exhibit greatly impaired splenic prion accumulation and replication throughout disease, similar to CD21/35-deficient murine prion protein mice infected with mouse scrapie. TgA5037;CD21/35−/− mice exhibited little or no neuropathology and deposition of misfolded, protease-resistant prion protein associated with CWD. CD21/35 translocate to lipid rafts and mediates a strong germinal center response to prion infection that we propose provides the optimal environment for prion accumulation and replication. We further propose a potential role for CD21/35 in selecting prion quasi-species present in prion strains that may exhibit differential zoonotic potential compared with the parental strains.
CD40/CD154 Blockade Inhibits Dendritic Cell Expression of Inflammatory Cytokines but Not Costimulatory Molecules
Authors: Ferrer Ivana R. , Liu Danya , Pinelli David F. , Koehn Brent H. , Stempora Linda L. , Ford Mandy L.
Published: September 2012

Blockade of the CD40/CD154 pathway remains one of the most effective means of promoting graft survival following transplantation. However, the effects of CD40/CD154 antagonism on dendritic cell (DC) phenotype and functionality following transplantation remain incompletely understood. To dissect the effects of CD154/CD40 blockade on DC activation in vivo, we generated hematopoietic chimeras in mice that expressed a surrogate minor Ag (OVA). Adoptive transfer of OVA-specific CD4+ and CD8+ T cells led to chimerism rejection, which was inhibited by treatment with CD154 blockade. Surprisingly, CD154 antagonism did not alter the expression of MHC and costimulatory molecules on CD11c+ DCs compared with untreated controls. However, DCs isolated from anti-CD154–treated animals exhibited a significant reduction in inflammatory cytokine secretion. Combined blockade of inflammatory cytokines IL-6 and IL-12p40 attenuated the expansion of Ag-specific CD4+ and CD8+ T cells and transiently inhibited the rejection of OVA-expressing cells. These results suggest that a major effect of CD154 antagonism in vivo is an impairment in the provision of signal three during donor-reactive T cell programming, as opposed to an impact on the provision of signal two. We conclude that therapies designed to target inflammatory cytokines during donor-reactive T cell activation may be beneficial in attenuating these responses and prolonging graft survival.
Cysteinyl Leukotriene 2 Receptor on Dendritic Cells Negatively Regulates Ligand-Dependent Allergic Pulmonary Inflammation
Authors: Barrett Nora A. , Fernandez James M. , Maekawa Akiko , Xing Wei , Li Li , Parsons Matthew W. , Austen K. Frank , Kanaoka Yoshihide
Published: September 2012

Cysteinyl leukotrienes (cys-LTs) can mediate Th2 immunity to the house dust mite, Dermatophagoides farinae, via the type 1 receptor CysLT1R on dendritic cells (DCs). However, the role of the homologous type 2 receptor CysLT2R in Th2 immunity is unknown. D. farinae sensitization and challenge of CysLT2R-deficient mice showed a marked augmentation of eosinophilic pulmonary inflammation, serum IgE, and Th2 cytokines. Wild-type (WT) mice sensitized by adoptive transfer of D. farinae-pulsed CysLT2R-deficient bone marrow-derived DCs (BMDCs) also had a marked increase in D. farinae-elicited eosinophilic lung inflammation and Th2 cytokines in restimulated hilar nodes. This response was absent in mice sensitized with D. farinae-pulsed BMDCs lacking leukotriene C4 synthase (LTC4S), CysLT1R, or both CysLT2R/LTC4S, suggesting that CysLT2R negatively regulates LTC4S- and CysLT1R-dependent DC-mediated sensitization. CysLT2R-deficient BMDCs had increased CysLT1R-dependent LTD4-induced ERK phosphorylation, whereas N-methyl LTC4 activation of CysLT2R on WT BMDCs reduced such signaling. Activation of endogenously expressed CysLT1R and CysLT2R occurred over an equimolar range of LTD4 and N-methyl LTC4, respectively. Although the baseline expression of cell surface CysLT1R was not increased on CysLT2R-deficient BMDCs, it was upregulated at 24 h by a pulse of D. farinae, compared with WT or CysLT2R/LTC4S-deficient BMDCs. Importantly, treatment with N-methyl LTC4 reduced D. farinae-induced CysLT1R expression on WT BMDCs. Thus, CysLT2R negatively regulates the development of cys-LT–dependent Th2 pulmonary inflammation by inhibiting both CysLT1R signaling and D. farinae-induced LTC4S-dependent cell surface expression of CysLT1R on DCs. Furthermore, these studies highlight how the biologic activity of cys-LTs can be tightly regulated by competition between these endogenously expressed receptors.
Coupling a groundwater model with a land surface model to improve water and energy cycle simulation
Authors: Tian W. , Li X. , Cheng G.-D. , Wang X.-S. , Hu B. X.
Published: September 2012

Abstract. Water and energy cycles interact, making these two processes closely related. Land surface models (LSMs) can describe the water and energy cycles on the land surface, but their description of the subsurface water processes is oversimplified, and lateral groundwater flow is ignored. Groundwater models (GWMs) describe the dynamic movement of the subsurface water well, but they cannot depict the physical mechanisms of the evapotranspiration (ET) process in detail. In this study, a coupled model of groundwater flow with a simple biosphere (GWSiB) is developed based on the full coupling of a typical land surface model (SiB2) and a three-dimensional variably saturated groundwater model (AquiferFlow). In this coupled model, the infiltration, ET and energy transfer are simulated by SiB2 using the soil moisture results from the groundwater flow model. The infiltration and ET results are applied iteratively to drive the groundwater flow model. After the coupled model is built, a sensitivity test is first performed, and the effect of the groundwater depth and the hydraulic conductivity parameters on the ET are analyzed. The coupled model is then validated using measurements from two stations located in shallow and deep groundwater depth zones. Finally, the coupled model is applied to data from the middle reaches of the Heihe River basin in the northwest of China to test the regional simulation capabilities of the model.
The link between great earthquakes and the subduction of oceanic fracture zones
Authors: Müller R. D. , Landgrebe T. C. W.
Published: September 2012

Abstract. Giant subduction earthquakes are known to occur in areas not previously identified as prone to high seismic risk. This highlights the need to better identify subduction zone segments potentially dominated by relatively long (up to 1000 yr and more) recurrence times of giant earthquakes. We construct a model for the geometry of subduction coupling zones and combine it with global geophysical data sets to demonstrate that the occurrence of great (magnitude ≥ 8) subduction earthquakes is strongly biased towards regions associated with intersections of oceanic fracture zones and subduction zones. We use a computational recommendation technology, a type of information filtering system technique widely used in searching, sorting, classifying, and filtering very large, statistically skewed data sets on the internet, to demonstrate a robust association and rule out a random effect. Fracture zone-subduction zone intersection regions, representing only 25% of the global subduction coupling zone, are linked with 13 of the 15 largest (magnitude (Mw ≥ 8.6) and half of the 50 largest, magnitude ≥ 8.4) earthquakes. In contrast, subducting volcanic ridges and chains are only biased towards smaller earthquakes (magnitude < 8). The associations captured by our statistical analysis can be conceptually related to physical differences between subducting fracture zones and volcanic chains/ridges. Fracture zones are characterized by laterally continuous, uplifted ridges that represent normal ocean crust with a high degree of structural integrity, causing strong, persistent coupling in the subduction interface. Smaller volcanic ridges and chains, not have a relatively fragile heterogeneous internal structure and are separated from the underlying ocean crust by a detachment interface, resulting in weak coupling and relatively small earthquakes, explaining the observed dichotomy.
Phytochemical Screening, Cytotoxicity, Antioxidant and Antimicrobial Activities of Stem and Leave Extracts of Euphorbia Heterophylla.
Authors: S.O. Okeniyi , B. J Adedoyin , S Garba
Published: September 2012

Phytochemical screening carried out on the stem and leave extracts of Euphorbia heterophylla (Euphorbieacea) confirmed the presence of Carbohydrates, gycosides, reducing sugar, saponins, taninns, phlobatanins, cardiac glycosides, steroids, triterpenes, and flavonoid. cytotoxicity test using brine shrimp lethality assay gave the LC50 value (µg/cm3 ) are 20.67, 25.07, 158.56,and 176.55 for n-Hexane fraction, Ethyl Acetate fraction, Butanol fraction and Aqueous fraction of the stem while 23.50, 30.20, 164.10 and 179.80 for n-hexane fraction, Ethyl Acetate fraction, Butanol fraction and Aqueous fraction of the leave extracts. The results of antioxidant properties of the stem and leaves extracts showed that the extracts exhibited strong activity as a radical scavenger in the experiment using 2, 2-diphenyl-1-picryhydrazyl radical (DPPH) indicating that the plant has strong ability to donate hydrogen when compared with the standard butyrate hydroxyl anisole (BHA). The antimicrobial activity of the extracts was carried out against Staphylococcus aureus, E.coli , Pseudomonas aeruginosa, Streptococcus pneumonia, and Candida albicans, the results showed moderate to low activity for the test organisms.
We still have a Long Way to go to Effectively Deliver Genes!
Authors: Pezzoli Daniele , Chiesa Roberto , De Nardo Luigi , Candiani Gabriele
Published: September 2012

Gene therapy is emerging as a revolutionary alternative to conventional therapeutic approaches. However, its clinical application is still hampered by the lack of safe and effective gene delivery techniques. Among the plethora of diverse approaches used to ferry nucleic acids into target cells, non-viral vectors represent promising and safer alternatives to viruses and physical techniques. Both cationic lipids and polymers spontaneously wrap and shrink the genetic material in complexes named lipoplexes and polyplexes, respectively, thereby protecting it and shielding its negative charges. The development of non-viral vectors commenced more than two decades ago. Since then, some major classes of interesting molecules have been identified and modified to optimize their properties. However, the way towards the final goal of gene delivery, i.e. protein expression or gene silencing, is filled with obstacles and current non-viral carriers still have concerns about their overall efficiency. We strongly believe that the future of non-viral gene delivery relies on the development of multifunctional vectors specifically tailored with diverse functionalities that act more like viruses. Although these vectors are still a long way from clinical practice they are the ideal platform to effectively shuttle the genetic material to target cells in a safe and controlled way. In this review, after briefly introducing the basis of gene delivery and therapeutic applications we discuss the main polymeric and lipidic vectors utilized for gene delivery, focusing on the strategies adopted to overcome the major weaknesses inherent to their still limited activity, on the way towards ideal multifunctional vectors.
Pullulan Production by Aureobasidium pullulans ATCC 201253 Cells Adsorbed onto Cellulose Anion and Cation Exchangers
Authors: West Thomas P.
Published: September 2012

The anion exchanger phosphocellulose and the cation exchanger triethylaminoethyl cellulose were used to immobilize cells of the fungus Aureobasidium pullulans ATCC 201253 and the adsorbed cells were subsequently investigated for their ability to produce the polysaccharide pullulan using batch fermentation. The cells adsorbed on the triethylaminoethyl cellulose at pH 7.5 produced higher pullulan levels than those cells immobilized on phosphocellulose at pH 4.0 for 2 cycles of 168 h at 30 °C. Relative to the initial cycle of 168 h, pullulan production by the cells immobilized on the triethylaminoethyl cellulose decreased slightly after 168 h of the second production cycle while pullulan production by the phosphocellulose-immobilized cells remained about the same after 168 h of the second production cycle.
Effect of Ethanol Content on Thermal Efficiency of a Spark-Ignition Light-Duty Engine
Authors: De Simio Luigi , Gambino Michele , Iannaccone Sabato
Published: September 2012

The use of bioethanol in the transport sector can contribute to mitigate the greenhouse gas emissions of the vehicles. To achieve this goal, together with a positive energy balance in global productive process of ethanol (well to tank), it is important that adding ethanol to gasoline does not cause a worsening of the efficiency of the internal combustion engine (tank to wheel). In this paper, a research activity on a commercial spark-ignition light-duty engine at the test bench is reported. The aim of the work was to characterize the effect of different bioethanol/gasoline blends on engine behaviour. Blends until 85% of ethanol were tested. Comparative studies of combustion development of gasoline and gasoline/ethanol blends at different concentrations have been made through the analysis of pressure cycles in combustion chamber. Moreover, emissions were collected and analyzed. Emissions downstream of the catalyst, measured with the blends, resulted quite similarly to the gasoline case. Instead, upstream the catalyst a reduction of emissions, proportional to oxygenated content was noted. Moreover, a general carbon dioxide reduction with ethanol blends was achieved due in particular to better engine thermal efficiency.
Diagnosing Arthrogryposis Multiplex Congenita: A Review
Authors: Kalampokas Emmanouil , Kalampokas Theodoros , Sofoudis Chrisostomos , Deligeoroglou Efthymios , Botsis Dimitrios
Published: September 2012

Arthrogryposis multiplex congenita (AMC) refers either to a syndromic or to a nonsyndromic group of conditions with varied etiology and complex clinical features, including multiple congenital contractures in different body areas. Its etiology still remains unclear but generally any cause that leads to reduced fetal movement may lead to congenital contractures and in severe cases to fetal akinesia deformation sequence (FADS).
It affects approximately 1 in 2-3000 live births with an approximately equal gender ratio. There are many known subgroups of AMC differing in signs, symptoms, and causes. The primary diagnosis is made when a lack of mobility and an abnormal position is noted in routine ultrasound scanning. Early diagnosis, prenatal evaluation, and further surveillance via image scanning (ultrasound and MRI) give the opportunity for family counseling concerning neonatal morbidity and mortality and labor or delivery planning. Better understanding of the ultrasound findings and the etiology of this clinical situation offers the opportunity for careful prenatal assessment.
Numerical Simulation of Viscous Flow over a Square Cylinder Using Lattice Boltzmann Method
Authors: Perumal D. Arumuga , Kumar Gundavarapu V. S. , Dass Anoop K.
Published: September 2012

This work is concerned with the lattice Boltzmann computation of two-dimensional incompressible viscous flow past a square cylinder confined in a channel. It is known that the nature of the flow past cylindrical obstacles is very complex. In the present work, computations are carried out both for steady and unsteady flows using lattice Boltzmann method. Effects of Reynolds number, blockage ratio, and channel length are studied in detail. As good care has been taken to include appropriate measures in the computational method, these results enjoy good credibility. To sum up, the present study reveals many interesting features of square cylinder problem and demonstrates the capability of the lattice Boltzmann method to capture these features.
Constrained Peptides as Miniature Protein Structures
Authors: Yin Hang
Published: September 2012

This paper discusses the recent developments of protein engineering using both covalent and noncovalent bonds to constrain peptides, forcing them into designed protein secondary structures. These constrained peptides subsequently can be used as peptidomimetics for biological functions such as regulations of protein-protein interactions.
Strong Law of Large Numbers for Hidden Markov Chains Indexed by Cayley Trees
Authors: Huang Huilin
Published: September 2012

We extend the idea of hidden Markov chains on lines to the situation of hidden Markov chains indexed by Cayley trees. Then, we study the strong law of large numbers for hidden Markov chains indexed by Cayley trees. As a corollary, we get the strong limit law of the conditional sample entropy rate.
Integration of Digital Dental Casts in Cone-Beam Computed Tomography Scans
Authors: Rangel Frits A. , Maal Thomas J. J. , Bergé Stefaan J. , Kuijpers-Jagtman Anne Marie
Published: September 2012

Cone-beam computed tomography (CBCT) is widely used in maxillofacial surgery. The CBCT image of the dental arches, however, is of insufficient quality to use in digital planning of orthognathic surgery. Several authors have described methods to integrate digital dental casts into CBCT scans, but all reported methods have drawbacks. The aim of this feasibility study is to present a new simplified method to integrate digital dental casts into CBCT scans. In a patient scheduled for orthognathic surgery, titanium markers were glued to the gingiva. Next, a CBCT scan and dental impressions were made. During the impression-taking procedure, the titanium markers were transferred to the impression. The impressions were scanned, and all CBCT datasets were exported in DICOM format. The two datasets were matched, and the dentition derived from the scanned impressions was transferred to the CBCT of the patient. After matching the two datasets, the average distance between the corresponding markers was 0.1 mm. This novel method allows for the integration of digital dental casts into CBCT scans, overcoming problems such as unwanted extra radiation exposure, distortion of soft tissues due to the use of bite jigs, and time-consuming digital data handling.
Longitudinal Observation of Japanese Lancelet,Branchiostoma japonicum, Metamorphosis
Authors: Kaji Takao , Hoshino Yoichi , Henmi Yasuhisa , Yasui Kinya
Published: September 2012

The lancelet (amphioxus) performs metamorphosis and produces minute and ciliate pelagic larvae commonly found in other metamorphic marine invertebrates. During larval life and metamorphosis, however, the animal displays interesting combination of features not found in other animals such as long coexistence of ciliate and muscular locomotion and no change in feeding behavior. The uniqueness of lancelet metamorphosis can provide important data to understand the evolutionary history of this animal as well as the metamorphosis broadly appeared in metazoans. Although lancelet metamorphosis has been studied, all previous studies depended on cross-sectional observations. To get serial data on metamorphic events, we performed longitudinal observations on the Japanese lancelet under the culture condition and confirmed the following: (1) there were individual variations of the duration of metamorphosis from 15 to 27 days; (2) growth was arrested for a month and the maximum reduction of the body length (2.2%–3.2%) occurred when gill slits became paired; (3) during rather long duration of metamorphosis, the oral transformation and the division of the gill pores by tongue bar were completed within two to four days. Our observations suggest that the duration and mode of lancelet metamorphosis depend mainly on intrinsic requirements rather than on extrinsic selective pressures.
Detailed Food Web Networks of Three Greater Antillean Coral Reef Systems: The Cayman Islands, Cuba, and Jamaica
Authors: Roopnarine Peter D. , Hertog Rachel
Published: September 2012

Food webs represent one of the most complex aspects of community biotic interactions. Complex food webs are represented as networks of interspecific interactions, where nodes represent species or groups of species, and links are predator-prey interactions. This paper presents reconstructions of coral reef food webs in three Greater Antillean regions of the Caribbean: the Cayman Islands, Cuba, and Jamaica. Though not taxonomically comprehensive, each food web nevertheless comprises producers and consumers, single-celled and multicellular organisms, and species foraging on reefs and adjacent seagrass beds. Species are grouped into trophic guilds if their prey and predator links are indistinguishable. The data list guilds, taxonomic composition, prey guilds/species, and predators. Primary producer and invertebrate richness are regionally uniform, but vertebrate richness varies on the basis of more detailed occurrence data. Each region comprises 169 primary producers, 513 protistan and invertebrate consumer species, and 159, 178, and 170 vertebrate species in the Cayman Islands, Cuba, and Jamaica, respectively. Caribbean coral reefs are among the world's most endangered by anthropogenic activities. The datasets presented here will facilitate comparisons of historical and regional variation, the assessment of impacts of species loss and invasion, and the application of food webs to ecosystem analyses.
Ancient Manioc Agriculture South of the Ceren Village, El Salvador
Authors: Sheets Payson , Lentz David , Piperno Dolores , Jones John , Dixon Christine , Maloof George , Hood Angela
Published: September 2012

The role of seed crops in the Maya diet is well understood. The role of root crops in the ancient Maya diet has been controversial, with some scholars suggesting they were staples, and others arguing they were not cultivated at all. Research in the 1990s found occasional manioc plants in kitchen gardens within the Classic period Cerén village, leading to the interpretation that manioc did contribute to the diet, but was not a staple. Recent research outside the village encountered sophisticated raised-bed monocropping of manioc over an extensive area. This area was harvested essentially all at once, about a week prior to the eruption. An estimated ten tons of tubers were harvested. The various uses of manioc include consumption as food, exchange with other settlements, fermentation, drying and storage as a powder, and as an adhesive. It is possible that many or all these alternatives were being followed. At Cerén manioc was a staple, not just an occasional adjunct to the diet. Because Cerén is toward the wet end of the ideal range for manioc cultivation, other areas of the Neotropics that receive less than 1,700 mm of precipitation may be more suitable for manioc cultivation than Cerén.
Un profil tiraillé entre des compétences bureaucratiques versus managériales pour les gestionnaires publics tunisiens1
Authors: Ben Hassine Anissa , Zeribi Olfa , Baouab Salma
Published: September 2012

L’objet de cette recherche est d’établir un profil des compétences des gestionnaires dans un secteur, l’administration publique, généralement peu porté sur les approches centrées sur les compétences. Pourtant, ces dernières pourraient largement, d’une part, favoriser la modernisation des pratiques publiques de gestion des ressources humaines et, d’autre part, les inscrire dans une perspective stratégique par rapport au modèle de l’administration publique recherché. Les résultats de cette étude, effectuée sur le terrain tunisien, montrent une tension entre des compétences que nous pouvons qualifier de bureaucratiques, avec une tendance à la verticalité des relations et au respect des procédures administratives, et d’autres que nous pouvons qualifier de managériales avec la recherche d’un meilleur partage des informations, une emphase sur l’éthique et sur le développement des capacités de gestion, de vision et de pilotage des politiques publiques. Des résultats qui indiqueraient qu’une certaine forme de New Weberian State serait en train de chercher à se mettre en place dans une administration publique tunisienne qui semble vouloir trouver en son sein les moyens de réinventer les solutions bureaucratiques tout en les adaptant aux défis du nouveau management public (Fabian, 2010).
La déviance comme mauvaise pratique : cas du système des marchés publics au Cameroun
Authors: Moungou Mbenda Sabine Patricia , Bekono Emmanuel Rémy
Published: September 2012

Des mauvaises pratiques apparaissent dans la gestion des marchés publics par les organisations publiques. L’objectif de cet article est d’esquisser des solutions pour les prévenir et les gérer, en appuyant leur compréhension sur le cas camerounais. Les données d’enquête auprès de 39 acteurs-clés montrent que certaines de ces pratiques contribuent à la performance organisationnelle et nourrissent un conflit entre les logiques administrative et managériale, sous l’arbitrage d’une logique politique porteuse de la légitimité du système. Les solutions esquissées portent sur les systèmes de management de risques, l’entente de gestion et la négociation des encadrements de gestion.
Development and Validation of a New Disease Activity Index as a Numerical Sum of Four Variables in Patients With Early Arthritis
Authors: Castrejón Isabel , Carmona Loreto , Ortiz Ana M. , Belmonte Miguel A. , Martínez‐López Juan A. , González‐Álvaro Isidoro
Published: September 2012

Objective

To describe the development and validation of a disease activity index in early arthritis that can be easily applied in daily practice and clinical research.

Methods

The Hospital Universitario La Princesa Index (HUPI) was developed after analysis of data from an early arthritis cohort (202 patients with 756 visits). It is the sum of 4 variables (graded 0–3): tender joint count, swollen joint count, patient global assessment, and acute‐phase reactants (erythrocyte sedimentation rate [ESR] and/or C‐reactive protein [CRP] level, depending on availability at the moment of evaluation). The score for each variable was based on its quartile distribution in the cohort. The HUPI was validated using the following properties: feasibility, internal consistency (Cronbach's alpha), convergent validity (Pearson's r coefficients with other activity measures), criterion validity (area under the receiver operating characteristic curve [AUC ROC] to detect minimal disease activity [MDA]), and sensitivity to change (AUC ROC) to detect change with the physician's and patient's assessment of disease activity.

Results

Internal consistency is reasonable (α = 0.63). The HUPI correlates well with activity measures such as the Disease Activity Score in 28 joints (DAS28; r = 0.89) and the Simplified Disease Activity Index (SDAI; r = 0.70), and correlates slightly worse with the functional index of the Health Assessment Questionnaire (r = 0.69). It discriminates MDA correctly (AUC 0.95), and its sensitivity to change is slightly superior (AUC 0.902) to that of the DAS28‐ESR (AUC 0.864), the DAS28‐CRP (AUC 0.889), and the SDAI (AUC 0.791).

Conclusion

The HUPI has face validity, is easy to calculate, is sensitive, and is a valid composite index for the assessment of disease activity in patients with early arthritis, both in clinical research and in routine care.
Interleukin‐13–producing CD8+ T cells mediate dermal fibrosis in patients with systemic sclerosis
Authors: Fuschiotti Patrizia , Larregina Adriana T. , Ho Johnan , Feghali‐Bostwick Carol , Medsger Thomas A.
Published: September 2012

Objective

Fibrosis is a major contributor to morbidity and mortality in systemic sclerosis (SSc). T cells are the predominant inflammatory infiltrate in affected tissue and are thought to produce cytokines that drive the synthesis of extracellular matrix (ECM) proteins by fibroblasts, resulting in excessive fibrosis. We have previously shown that aberrant interleukin‐13 (IL‐13) production by peripheral blood effector CD8+ T cells from SSc patients correlates with the extent of skin fibrosis. The present study was undertaken to investigate the role of IL‐13 production by CD8+ T cells in dermal fibrosis, an early and specific manifestation of SSc.

Methods

ECM protein production by normal dermal fibroblasts cocultured with SSc CD8+ T cell supernatants was determined by quantitative polymerase chain reaction and Western blotting. Skin‐homing receptor expression and IL‐13 production by CD8+ T cells in the peripheral blood of SSc patients were measured by flow cytometry. IL‐13+ and CD8+ cells in sclerotic skin were identified by immunohistochemistry.

Results

IL‐13–producing circulating CD8+ T cells from patients with SSc expressed skin‐homing receptors and induced a profibrotic phenotype in normal dermal fibroblasts, which was inhibited by an anti–IL‐13 antibody. High numbers of CD8+ T cells and IL‐13+ cells were found in the skin lesions of SSc patients, particularly during the early inflammatory phase of the disease.

Conclusion

These findings show that IL‐13–producing CD8+ T cells are directly involved in modulating dermal fibrosis in SSc. The demonstration that CD8+ T cells homing to the skin early in the course of SSc are associated with accumulation of IL‐13 is an important mechanistic contribution to the understanding of the pathogenesis of dermal fibrosis in SSc and may represent a potential target for therapeutic intervention.
The TTTT B lymphocyte stimulator promoter haplotype is associated with good response to rituximab therapy in seropositive rheumatoid arthritis resistant to tumor necrosis factor blockers
Authors: Fabris Martina , Quartuccio Luca , Vital Ed , Pontarini Elena , Salvin Sara , Fabro Cinzia , Zabotti Alen , Benucci Maurizio , Manfredi Mariangela , Ravagnani Viviana , Biasi Domenico , Atzeni Fabiola , Sarzi‐Puttini Piercarlo , Morassi Pia , Fischetti Fabio , Bazzicchi Laura , Saracco Marta , Pellerito Raffaele , Cimmino Marco , Carraro Valeria , Semeraro Angelo , Schiavon Franco , Caporali Roberto , Bortolotti Roberto , Govoni Marcello , Fogolari Federico , Tonutti Elio , Bombardieri Stefano , Emery Paul , De Vita Salvatore
Published: September 2012

Objective

To investigate the polymorphisms in the promoter region of the B lymphocyte stimulator (BLyS) gene as markers of response to rituximab (RTX) in rheumatoid arthritis (RA).

Methods

The study was first conducted in 152 Italian RA patients and then replicated in an additional 117 RA patients (73 Italian, 44 British). The European League Against Rheumatism response criteria were used to evaluate the response rate at months 4 and 6 after the first cycle of RTX, by means of the Disease Activity Score in 28 joints using the erythrocyte sedimentation rate; patients were classified according to the best response shown between months 4 and 6. BLyS promoter polymorphisms were analyzed by polymerase chain reaction followed by the analysis of the restriction fragments, BLyS promoter haplotypes were analyzed using the expectation‐maximization algorithm, and BLyS serum levels were analyzed using enzyme‐linked immunosorbent assay. Odds ratios (ORs) were calculated with 95% confidence intervals (95% CIs).

Results

The TTTT BLyS promoter haplotype appeared to be significantly associated with response to RTX only in the subset of seropositive patients (those positive for rheumatoid factor and/or anti–cyclic citrullinated peptide). The replication study confirmed that this association was limited to seropositive RA patients in whom treatment with anti–tumor necrosis factor (anti‐TNF) agents had previously failed. In the whole series of seropositive patients in whom anti‐TNF agents had previously failed, patients carrying the TTTT BLyS promoter haplotype were more prevalent in good responders (18 of 43 [41.9%]) than in moderate responders (20 of 83 [24.1%]) or in nonresponders (1 of 21 [4.8%]) (for good responders versus nonresponders, OR 14.4 [95% CI 1.77–117.39], P = 0.0028). Furthermore, multivariate analysis selected the TTTT BLyS promoter haplotype as an independent marker of good response to RTX (for good responders versus nonresponders, OR 16.2 [95% CI 1.7–152.5], P = 0.01; for good responders versus moderate responders and nonresponders combined, OR 3.1 [95% CI 1.2–7.8], P = 0.02). The relationship between BLyS polymorphisms and BLyS serum levels remained unclear.

Conclusion

BLyS promoter genotyping may be suitable for identifying seropositive RA patients who may have a good response to RTX after anti‐TNF agents have failed.
Identification of a susceptibility locus in STAT4 for Behçet's disease in Han Chinese in a genome‐wide association study
Authors: Hou Shengping , Yang Zhenglin , Du Liping , Jiang Zhengxuan , Shu Qinmeng , Chen Yuanyuan , Li Fuzhen , Zhou Qingyun , Ohno Shigeaki , Chen Rui , Kijlstra Aize , Rosenbaum James T. , Yang Peizeng
Published: September 2012

Objective

To identify susceptibility loci for Behçet's disease (BD) and elucidate their functional role.

Methods

A genome‐wide association study (GWAS) and functional studies were conducted. A total of 149 patients and 951 controls were enrolled in the initial GWAS, and 554 patients and 1,159 controls were enrolled in the replication study. Real‐time polymerase chain reaction, luciferase reporter assay, and enzyme‐linked immunosorbent assay were performed.

Results

Our GWAS and replication studies identified a susceptibility locus around STAT4 (single‐nucleotide polymorphisms [SNPs] rs7574070, rs7572482, and rs897200; P = 3.36 × 10−7 to 6.20 × 10−9). Increased expression of STAT4 was observed in individuals carrying the rs897200 risk genotype AA. Consistent with the idea that STAT4 regulates the production of interleukin‐17 (IL‐17) and interferon‐γ, IL17 messenger RNA and protein levels were increased in individuals carrying the rs897200 risk genotype AA. Interestingly, the risk allele A of rs897200 creates a putative transcription factor binding site. To test whether it directly affects STAT4 transcription, an in vitro luciferase reporter gene assay was performed. Higher transcription activity was observed in individuals carrying the risk allele A, suggesting that rs897200 is likely to directly affect STAT4 expression. Additionally, 2 SNPs, rs7574070 and rs7572482, which are tightly linked with rs897200, were cis‐expression quantitative trait loci (eQTL) SNPs, suggesting that SNP rs897200 is an eQTL SNP. Most importantly, the clinical disease severity score was higher in individuals with the rs897200 risk genotype AA.

Conclusion

These findings strongly suggest that STAT4 is a novel locus underlying BD. We propose a model in which up‐regulation of STAT4 expression and subsequent STAT4‐driven production of inflammatory cytokines, such as IL‐17, constitute a potential pathway leading to BD.
Efficacy of B cell depletion therapy for murine joint arthritis flare is associated with increased lymphatic flow
Authors: Li Jie , Ju Yawen , Bouta Echoe M. , Xing Lianping , Wood Ronald W. , Kuzin Igor , Bottaro Andrea , Ritchlin Christopher T. , Schwarz Edward M.
Published: September 2012

Objective

B cell depletion therapy ameliorates rheumatoid arthritis by mechanisms that are incompletely understood. Arthritis flare in tumor necrosis factor (TNF)–transgenic mice is associated with efferent lymph node (LN) “collapse,” triggered by B cell translocation into lymphatic spaces and decreased lymphatic drainage. The aim of this study was to examine whether the efficacy of B cell depletion therapy is associated with restoration of lymphatic drainage due to removal of obstructing nodal B cells.

Methods

We used contrast‐enhanced magnetic resonance imaging, indocyanine green near‐infrared imaging, and intravital immunofluorescence imaging to longitudinally assess synovitis, lymphatic flow, and cell migration in lymphatic vessels in TNF‐transgenic mice. We conducted tests to determine whether the efficacy of B cell depletion therapy is associated with restoration of lymphatic draining and cell egress from arthritic joints.

Results

Unlike active lymphatics to normal and prearthritic knees, afferent lymphatic vessels to collapsed LNs in inflamed knees do not pulse. Intravital immunofluorescence imaging demonstrated that CD11b+ monocyte/macrophages in lymphatic vessels afferent to expanding LNs travel at high velocity (mean ± SD 186 ± 37 μm/second), while these cells are stationary in lymphatic vessels afferent to collapsed popliteal LNs. B cell depletion therapy for arthritis flares in TNF‐transgenic mice significantly decreased knee synovium volume (by 50% from the baseline level) and significantly increased lymphatic clearance compared with placebo (P < 0.05). This increased lymphatic drainage restored macrophage egress from inflamed joints without recovery of the lymphatic pulse.

Conclusion

These results support a novel mechanism in which B cell depletion therapy for joint arthritis flares lessens inflammation by increasing lymphatic drainage and subsequent migration of cells and cytokines from the synovial space.
Differential expression of junctional adhesion molecules in different stages of systemic sclerosis
Authors: Manetti Mirko , Guiducci Serena , Romano Eloisa , Rosa Irene , Ceccarelli Claudia , Mello Tommaso , Milia Anna Franca , Conforti Maria Letizia , Ibba‐Manneschi Lidia , Matucci‐Cerinic Marco
Published: September 2012

Objective

Systemic sclerosis (SSc) is characterized by early perivascular inflammation, microvascular endothelial cell (MVEC) activation/damage, and defective angiogenesis. Junctional adhesion molecules (JAMs) regulate leukocyte recruitment to sites of inflammation and ischemia‐reperfusion injury, vascular permeability, and angiogenesis. This study was undertaken to investigate the possible role of JAMs in SSc pathogenesis.

Methods

JAM‐A and JAM‐C expression levels in skin biopsy samples from 25 SSc patients and 15 healthy subjects were investigated by immunohistochemistry and Western blotting. Subcellular localization of JAMs in cultured healthy dermal MVECs and SSc MVECs was assessed by confocal microscopy. Serum levels of soluble JAM‐A (sJAM‐A) and sJAM‐C in 64 SSc patients and 32 healthy subjects were examined by enzyme‐linked immunosorbent assay.

Results

In control skin, constitutive JAM‐A expression was observed in MVECs and fibroblasts. In early‐stage SSc skin, JAM‐A expression was strongly increased in MVECs, fibroblasts, and perivascular inflammatory cells. In late‐stage SSc, JAM‐A expression was decreased compared with controls. JAM‐C was weakly expressed in control and late‐stage SSc skin, while it was strongly expressed in MVECs, fibroblasts, and inflammatory cells in early‐stage SSc. Surface expression of JAM‐A was higher in early‐stage SSc MVECs and increased in healthy MVECs stimulated with early‐stage SSc sera. JAM‐C was cytoplasmic in resting healthy MVECs, while it was recruited to the cell surface upon challenge with early‐stage SSc sera. Early‐stage SSc MVECs exhibited constitutive surface JAM‐C expression. In SSc, increased levels of sJAM‐A and sJAM‐C correlated with early disease and measures of vascular damage.

Conclusion

Our findings indicate that JAMs may participate in MVEC activation, inflammatory processes, and impaired angiogenesis in different stages of SSc.
Perylene Bisimide Dimer Aggregates: Fundamental Insights into Self‐Assembly by NMR and UV/Vis Spectroscopy
Authors: Shao Changzhun , Grüne Matthias , Stolte Matthias , Würthner Frank
Published: September 2012

A novel perylene bisimide (PBI) dye bearing one solubilizing dialkoxybenzyl and one bulky 2,5‐di‐tert‐butylphenyl substituent was synthesized and its aggregation behavior was analyzed by NMR and UV/Vis spectroscopy in various chloroform/methylcyclohexane (MCH) solvent mixtures. In the presence of no less than 10 vol % chloroform, exclusive self‐assembly of this PBI dye into π‐stacked dimers was unambiguously confirmed by means of both concentration‐dependent 1H NMR and UV/Vis spectroscopic experiments. Based on ROESY NMR, a well‐defined π‐stacked dimer structure was determined and further corroborated by molecular modeling studies. By varying the solvent composition of chloroform and MCH, the solvent effects on the Gibbs free energy of PBI dimerization were elucidated and showed a pronounced nonlinearity between lower and higher MCH contents. This observation could be related to a further growth process of dimers into larger aggregates that occurs in the absence of chloroform, which is required to solvate the aromatic π surfaces. With the help of a single‐crystal structure analysis for a related PBI dye, a structural model could be derived for the extended aggregates that are still composed of defined π–π‐stacked PBI dimer entities.
A New Mussel‐Inspired Polydopamine Sensitizer for Dye‐Sensitized Solar Cells: Controlled Synthesis and Charge Transfer
Authors: Nam Hye Jin , Kim Boeun , Ko Min Jae , Jin Mingshi , Kim Ji Man , Jung Duk‐Young
Published: September 2012

The efficient electron injection by direct dye‐to‐TiO2 charge transfer and strong adhesion of mussel‐inspired synthetic polydopamine (PDA) dyes with TiO2 electrode is demonstrated. Spontaneous self‐polymerization of dopamine using dip‐coating (DC) and cyclic voltammetry (CV) in basic buffer solution were applied to TiO2 layers under a nitrogen atmosphere, which offers a facile and reliable synthetic pathway to make the PDA dyes, PDA‐DC and PDA‐CV, with conformal surface and perform an efficient dye‐to‐TiO2 charge transfer. Both synthetic methods led to excellent photovoltaic results and the PDA‐DC dye exhibited larger current density and efficiency values than those in the PDA‐CV dye. Under simulated AM 1.5 G solar light (100 mW cm−2), a PDA‐DC dye exhibited a short circuit current density of 5.50 mW cm−2, corresponding to an overall power conversion efficiency of 1.2 %, which is almost 10 times that of the dopamine dye‐sensitized solar cell. The PDA dyes showed strong adhesion with the nanocrystalline TiO2 electrodes and the interface engineering of a dye‐adsorbed TiO2 surface through the control of the coating methods, reaction times and solution concentration maximized the overall conversion efficiency, resulting in a remarkably high efficiency.
Analogue portable electrooculogram real‐time signal processor
Authors: Fricke Kyle , Sobot Robert , Dounavis Anestis
Published: September 2012

We present an analogue signal‐processing circuit suitable for applications in a portable, wearable, non‐invasive electrooculogram‐based human–computer interface. Behavioural model and preliminary experimental results confirm that the proposed circuit, while operating in real time, correctly detects and decodes signals generated by the subject's eye movements. The total power consumption is measured at 145 mW (excluding the RF link) with a 3 V power supply voltage, and the unit size is approximately 5 cm × 3 cm printed circuit board. Copyright © 2012 John Wiley & Sons, Ltd.
Mouse models of DNA polymerases
Authors: Menezes Miriam R. , Sweasy Joann B.
Published: September 2012

In 1956, Arthur Kornberg discovered the mechanism of the biological synthesis of DNA and was awarded the Nobel Prize in Physiology or Medicine in 1959 for this contribution, which included the isolation and characterization of Escherichia coli DNA polymerase I. Now there are 15 known DNA polymerases in mammalian cells that belong to four different families. These DNA polymerases function in many different cellular processes including DNA replication, DNA repair, and damage tolerance. Several biochemical and cell biological studies have provoked a further investigation of DNA polymerase function using mouse models in which polymerase genes have been altered using gene‐targeting techniques. The phenotypes of mice harboring mutant alleles reveal the prominent role of DNA polymerases in embryogenesis, prevention of premature aging, and cancer suppression.