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•Electrically activated thermal storage system can be used for peak shaving of a residential building.•A validated model was used to investigate various system configurations and control strategies.•Design guidelines for the integration of the system both in terms of its construction and its control have proposed.

•Integration of heat extraction system with EHF is proposed for peak shifting/shaving.•The influence of inter-zonal airflow on model accuracy is studied.•The proposed system augments the peak shifting potential of EHF by 19%.•Also, potential in reduction of heating cost by 24% is explored.•The proposed system will be a benefit for both the supplier and consumer.

Évaluer l’effet antalgique d’une prise orale de paracétamol versus placebo chez l’adulte, en soins primaires.

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ABSTRACTThe presence of HIV-1 non-B subtypes in Western Europe is commonly attributed to migration of individuals from non-European countries, but the possible role of domestic infections with non-B subtypes is not well investigated. The French mandatory anonymous reporting system for HIV is linked to a virological surveillance using assays for recent infection (<6 months) and serotyping. During the first semester of years 2007 to 2010, any sample corresponding to a non-B recent infection was analyzed by sequencing a 415-bp envregion, followed by phylogenetic analysis and search for transmission clusters. Two hundred thirty-three recent HIV-1 infections with non-B variants were identified. They involved 5 subtypes and 7 circulating recombinant forms (CRFs). Ninety-two cases (39.5%) were due to heterosexual transmissions, of which 39 occurred in patients born in France. Eighty-five cases (36.5%) were identified in men having sex with men (MSM). Forty-three recent non-B infections (18.5%) segregated into 14 clusters, MSM being involved in 11 of them. Clustered transmission events included 2 to 7 cases per cluster. The largest cluster involved MSM infected by a CRF02_AG variant. In conclusion, we found that the spread of non-B subtypes in France occurs in individuals of French origin and that MSM are particularly involved in this dynamic.

ABSTRACTAmong 61 and 35 patients who were infected in France by viruses of the rare clades D and CRF01_AE, respectively, approximately half of them originated from areas where HIV-1 is endemic, but the data showed that both clades have spread in the French indigenous population, particularly in men having sex with men (MSM).

La scoliose est la déformation la plus fréquente en orthopédie pédiatrique. Elle survient principalement à l’adolescence affectant les filles en plus grand nombre et avec le plus de sévérité. Nos travaux ont mis en évidence un défaut dans la transmission du signal de l’hormone mélatonine chez des patients gravement atteints de scoliose idiopathique de l’adolescent (SIA). Cette anomalie est causée par la phosphorylation de résidus sérine au niveau des protéines G inhibitrices (Gi) couplées aux récepteurs à mélatonine. Nous avons observé chez les patients SIA trois types de réponses anormales en présence de mélatonine ce qui suggère que ce défaut est attribuable à des gènes distincts en cause dans cette voie de signalisation. Cette découverte nous a permis de mettre au point un premier test de dépistage précoce à partir d’une simple prise de sang. Actuellement en cours de validation clinique au Canada, ce test devrait permettre l’identification des enfants porteurs du risque de développer une SIA

In the present study, we have investigated the effect of (i) ET-1 (endothelin-1) and its precursor, big ET-1, on MMP (matrix metalloproteinase)-2 and MMP-9 synthesis and activity in osteosarcoma tissue, and (ii) ET-1 receptor antagonists on cell invasion. Using Western blotting, zymography, RT-PCR (reverse transcription–PCR), immunohistochemistry, immunofluorescence and Northern blotting, we have shown that ET-1 and ET-1 receptors (ETA and ETB) were expressed in these cells. Additionally, we have demonstrated that ET-1 markedly induced the synthesis and activity of MMP-2, which was significantly increased when compared with MMP-9. Furthermore, inhibition of NF-κB (nuclear factor κB) activation blocked MMP-2 production and activity, indicating the involvement of NF-κB, a ubiquitous transcription factor playing a central role in the differentiation, proliferation and malignant transformation. Since ET-1 acts as an autocrine mediator through gelatinase induction and because inhibition of ETA receptor is beneficial for reducing both basal and ET-1-induced osteosarcoma cell invasion, targeting this receptor could be an attractive therapeutic alternative for the successful treatment of osteosarcoma.

Avec l’utilisation du placebo au sein des essais cliniques contrôlés depuis 50 ans, il semble qu’on puisse objectiver et mesurer les effets psychophysiologiques liés à la thérapeutique regroupés sous le terme « effet placebo ». Depuis l’article de référence de Beecher en 1955, il est admis et mentionné dans de nombreux articles médicaux que son efficacité est de 35 % en moyenne dans la plupart des symptômes. Or, il apparaît que la signification de cette mesure est erronée. Elle ne prend pas en compte par exemple l’évolution spontanée des symptômes et des maladies. En fait, l’effet placebo n’est pas l’effet mesuré dans le groupe traité par le placebo. L’essai clinique contrôlé médicament contre placebo ne permet pas de mesurer ce qu’on appelle donc à tort « l’effet placebo ». Peut-on alors mesurer et objectiver ce qu’on appelle « l’effet placebo » ? Si cela est possible, de quelle manière ? Cet article remet en question l’ampleur de l’effet placebo évaluée au moyen des essais cliniques contrôlés sans pour autant nier son importance en pratique soignante. Il soulève d’une part, le problème épistémologique de la possibilité réelle d’objectiver les effets psychologiques de la thérapeutique, via l’expérimentation et d’autre part, il pose la question de l’intérêt pour la pratique soignante, à l’heure de la médecine fondée sur les preuves et de les objectiver.

ABSTRACTWe report a case of human immunodeficiency virus type 1 group O infection not detected by two highly sensitive immunoassays. The sera were strongly reactive to the V3 peptide of group O but not to the gp41 immunodominant epitope. Gp41 was sequenced, confirming that this virus belonged to group O.

We report a case of human immunodeficiency virus type 1 group O infection not detected by two highly sensitive immunoassays. The sera were strongly reactive to the V3 peptide of group O but not to the gp41 immunodominant epitope. Gp41 was sequenced, confirming that this virus belonged to group O.

Many studies have demonstrated the utility of the dried blood spot (DBS) or dried plasma/serum spot (DSS) method for serological and molecular diagnosis of HIV infection. Here, we report on the description of a serotyping assay performed on DSS, and its application to a national surveillance program of HIV variants. We combined serotyping assays that we developed previously to discriminate between HIV‐1 and HIV‐2, between HIV‐1 group O and HIV‐1 group M, and between B and non‐B subtypes of HIV‐1 group M. The assays are based on antibody binding to either the immunodominant epitope of gp41 or the V3 domain of gp120 of these various types, groups and subtypes. Therefore, a unique enzyme‐linked immunosorbent assay (ELISA) format applied to serum eluted from DSS allowed the simultaneous discrimination between infections caused by HIV‐1 B, HIV‐1 non‐B, HIV‐1 group O, and HIV‐2. Together, this serotyping assay and an immunoassay for recent infection were used for a virological surveillance linked to the anonymous mandatory notification of HIV infection in France. The preliminary results of this virological surveillance allowed us to obtain estimates of the prevalence of the rare variants HIV‐2 and HIV‐1 group O. It also allowed identification of the two first cases of M/O dual infections reported outside the endemic group O region of the western part of equatorial Africa, and showed that non‐B subtypes circulate widely in France, almost 50% of new HIV diagnoses in 2003 being due to these variants. J. Med. Virol. 78:S13–S18, 2006. © 2006 Wiley‐Liss, Inc.

ABSTRACTThe hepatitis C virus (HCV) envelope protein 2 (E2) interacts in vitro with the interferon alpha (IFN-a)-inducible double-stranded RNA-activated protein kinase, suggesting a possible mechanism by which HCV may evade the antiviral effects of IFN-a. Variability in the part of the HCV E2 gene encoding the carboxy-terminal part of the protein, which includes the interaction domain (E2-PePHD), was explored in 25 patients infected with HCV genotype 1b and receiving IFN-a therapy. PCR products were generated and sequenced for 15 patients with a sustained response and for 10 patients with no virological response after treatment with IFN-a and ribavirin. PePHD amino acid sequences were obtained for isolates from serum collected before and during treatment, after 2 months in responders, and after 6 months in nonresponders. Quasispecies analysis of the pretreatment PePHD region was performed for isolates from patients displaying amino acid substitutions in this domain on direct sequencing. The E2-PePHD sequence was highly conserved in both resistant and susceptible genotype 1b strains and was identical to the prototype HCV type J sequence. No significant emergence of PePHD mutants during therapy was observed in our clonal analysis, and sporadic mutations and treatment outcomes were not found to be correlated. The PePHD sequence before or during treatment cannot be used to predict reliably the outcome of treatment in HCV type 1b-infected patients.

ABSTRACTThe heterogeneity of hypervariable region 1 (HVR1), located at the amino terminus of the E2 envelope, may be involved in resistance to alpha interferon (IFN-a) treatment. We investigated whether peculiar HVR1 domain profiles before treatment were associated with the maintenance of sensitivity or the appearance of resistance to treatment. Fifteen patients infected with hepatitis C virus genotype 1b and treated with IFN with or without ribavirin were selected. Ten responded to treatment (groups R1 and R2) and five did not (group NR). The amino acid sequences of 150 naturally occurring HVR1 variants present in the serum before therapy were compared in relation to treatment outcome. HVR1 variants from the NR group contained a constant nonantigenic amino acid segment that was not found in HVR1 variants from the R groups.

In 94 patients with chronic hepatitis C, the pattern of integrin expression was correlated with firstly, the histological activity index, necro‐inflammatory grade, and stage of fibrosis; secondly, the expression of inflammatory markers including ICAM‐1; and thirdly, the extent and intensity of laminin deposition in the perisinusoidal matrix. Immunohistochemical results were evaluated according to a semi‐quantitative scoring system or by image analysis. Increased β1 expression was observed in 88.2% of cases. The expression of α1 and α5 was increased in 55% and 58.5% of cases, respectively. α6 chain was detected in 78.7% of cases. There were no statistically significant differences in integrin expression level according to Knodell's score, inflammatory grade, or stage of fibrosis. ICAM‐1 expression was higher in patients with high scores for β1 expression, but the differences were not statistically significant. There were significantly more patients with high scores for β1 expression among those with continuous perisinusoidal deposition of laminin. Moreover, a close statistical correlation was observed between α6 induction and perisinusoidal laminin deposition (p<0.001). The results suggest that integrin up‐regulation in chronic hepatitis C is more closely related to the fibrotic process than to the inflammatory lesions. This reinforces the idea that integrin induction in chronic liver disease is part of a coordinated process involved in the progression of liver fibrosis. Copyright © 2001 John Wiley & Sons, Ltd.

Originellement le périple des Argonautes se situe dans un pays du bout du monde, un pays de nulle part. Mais à partir du VIe siècle la colonisation grecque joue un rôle fondamental dans l’extension du voyage d’Argo : comme un nouveau riche qui se dote d’une particule, les nouvelles cités veulent se donner le prestige de l’ancienneté. C’est pourquoi leurs historiensgéographes inventent sans cesse de nouvelles étapes argonautiques qui conduisent les héros de plus en plus loin vers l’ouest et le nord au fur et à mesure des découvertes des navigateurs grecs.

The restricted expression of the Ptx1 (Pitx1) gene in the posterior half of the lateral plate mesoderm has suggested that it may play a role in specification of posterior structures, in particular, specification of hindlimb identity. Ptx1 is also expressed in the most anterior ectoderm, the stomodeum, and in the first branchial arch. Ptx1 expression overlaps with that of Ptx2 in stomodeum and in posterior left lateral plate mesoderm. We now show that targeted inactivation of the mouse Ptx1 gene severely impairs hindlimb development: the ilium and knee cartilage are absent and the long bones are underdeveloped. Greater reduction of the right femur size in Ptx1 null mice suggests partial compensation by Ptx2 on the left side. The similarly sized tibia and fibula of mutant hindlimbs may be taken to resemble forelimb bones: however, the mutant limb buds appear to have retained their molecular identity as assessed by forelimb expression of Tbx5 and by hindlimb expression of Tbx4, even though Tbx4 expression is decreased in Ptx1 null mice. The hindlimb defects appear to be, at least partly, due to abnormal chondrogenesis. Since the most affected structures derive from the dorsal side of hindlimb buds, the data suggest that Ptx1 is responsible for patterning of these dorsal structures and that as such it may control development of hindlimb-specific features. Ptx1 inactivation also leads to loss of bones derived from the proximal part of the mandibular mesenchyme. The dual role of Ptx1 revealed by the gene knockout may reflect features of the mammalian jaw and hindlimbs that were acquired at a similar time during tetrapod evolution.

Background/Aims:Somatic cells are protected against complement-mediated injury by specialized membrane proteins, known as complement-regulatory proteins (CRP). The knowledge of the pattern of CRP expression in the liver is important to evaluate the role of complement-mediated injury in graft rejection. Methods:We determined the distribution of four main CRP: membrane cofactor protein (MCP), decay accelerating factor (DAF), protectin, and complement receptor 1 (CR1) in 30 histologically normal livers, 13 samples from University of Wisconsin cold-storage solution (UW)-preserved tissue and 17 postoperative biopsies of UW-preserved allografts. Results:In normal liver, hepatocytes expressed only MCP. Bile duct cells were reactive for MCP and protectin. Sinusoidal endothelial cells expressed MCP and protectin but displayed no or faint expression of DAF. Endothelial cells of portal vessels and centrilobular veins expressed high levels of DAF, MCP, and protectin. No expression of CR1 was observed. No change in CRP expression was usually detected after UW preservation, except for protectin, induced on hepatocytes in 9 samples of UW-preserved liver tissue and in 9 allografts. Conclusions:Hepatocytes and sinusoidal endothelial cells, which have a defective expression of CRP, might be at risk for complement-mediated injury. However, this risk is not aggravated after UW preservation.

The coexpression of normally periportal and perivenous markers has been described in heterotopically transplanted hepatocytes. To determine whether such a coexpression might also occur in hepatocytes retaining their original intrahepatic location, we compared in bileduct-ligated livers and intrasplenically transplanted hepatocytes, the expression and distribution of the predominantly periportal glucose-6-phosphatase, succinate dehydrogenase, and lactate dehydrogenase, the predominantly perivenous glutamate dehydrogenase, NADPH-dehydrogenase, and ß-hydroxybutyrate dehydrogenase, and the strictly perivenous glutamine synthetase. The coexpression of high levels of the two periportal markers glucose-6-phosphatase and lactate dehydrogenase and of the perivenous marker NADPH dehydrogenase was observed in two situations: in clusters of hepatocytes isolated within the ductular proliferation in bile-duct-ligated livers and the majority of intrasplenically transplanted hepatocytes. The expression of glutamine synthetase was different according to the site. The protein was observed in certain intrasplenically transplanted hepatocytes bordering the splenic vessels but was never detected in hepatocyte clusters found in bile-duct-ligated livers. Our study therefore suggests that the coexpression of periportal and perivenous markers in the same hepatocytes is likely to be a non-specific consequence of the loss of the normal connections of hepatocytes with the normal liver microcirculation.

Quatorze cas de décapitation projetée ou réalisée recensés dans l'Illiade sont presque toujours expliqués par Homère au moyen d’une motivation psychologique : on veut faire payer à l’adversaire la mort d’un frère ou d ’un ami cher. L'acte est donc présente comme exceptionnel, et non comme intégré dans les rites d’une société. Et pourtant la comparaison avec les pratiques d ’autres peuples (Scythes, Celtes, Germains) conduit à penser que chez les Grecs comme chez ceux qu'ils appellent Barbares le rite de la décapitation s'inscrit dans le cadre d’épreuves initiatiques, et notamment celles qui se déroulent au moment de l’adolescence. Cette constatation est confirmée par l’examen de plusieurs mythes grecs ou l’on trouve des décapitations.

AbstractThe alignment of the promoter region of several Streptomycesxylanases shows three conserved sequences which could be involved in gene regulation. By electromobility shift assays these specific sequences, present only in Streptomycesxylanolytic strains, were identified as protein‐binding sites. The sequence required for efficient recognition by the retarding protein appeared to be a 4‐bp inverted repeat: 5′‐CTTT‐Nx‐AAAG‐3′. The DNA‐protein affinity was influenced by the culture conditions.

ABSTRACTThe alpha chain of the nascent polypeptide-associated complex (α-NAC) coactivator was shown to potentiate the activity of the homodimeric c-Jun activator, while transcription mediated by the c-Fos/c-Jun heterodimer was unaffected. The use of deletion mutants in pull-down assays revealed that α-NAC interacted with amino acids 1 to 89 of the c-Jun protein and that the coactivator could interact with both the unphosphorylated and the serine 73-phosphorylated form of c-Jun. N-terminal-deleted c-Jun protein failed to interact with α-NAC in mammalian two-hybrid assays, while mutant c-Jun proteins lacking the leucine zipper or the basic domain retained interaction with α-NAC in vivo. Kinetics studies with purified c-Jun homodimer and recombinant α-NAC proteins allowed determination of the mechanism of coactivation by α-NAC: the coactivator stabilized the AP-1 complex formed by the c-Jun homodimer on its DNA recognition sequence through an eightfold reduction in the dissociation constant (kd) of the complex. This effect of α-NAC was specific, because α-NAC could not stabilize the interactions of JunB or Sp1 with their cognate binding sites. Interestingly, the expression of α-NAC was first detected at 14.5 to 15 days postconception, concomitantly with the onset of ossification during embryogenesis. The α-NAC protein was specifically expressed in differentiated osteoblasts at the centers of ossification. Thus, the α-NAC gene product exhibits the properties of a developmentally regulated, bone-specific transcriptional coactivator.

ABSTRACTWe report the characterization of clone 1.9.2, a gene expressed in mineralizing osteoblasts. Remarkably, clone 1.9.2 is the murine homolog of the alpha chain of the nascent polypeptide-associated complex (α-NAC). Based on sequence similarities between α-NAC/1.9.2 and transcriptional regulatory proteins and the fact that the heterodimerization partner of α-NAC was identified as the transcription factor BTF3b (B. Wiedmann, H. Sakai, T. A. Davis, and M. Wiedmann, Nature 370:434–440, 1994), we investigated a putative role for α-NAC/1.9.2 in transcriptional control. The α-NAC/1.9.2 protein potentiated by 10-fold the activity of the chimeric activator GAL4/VP-16 in vivo. The potentiation was shown to be mediated at the level of gene transcription, because α-NAC/1.9.2 increased GAL4/VP-16-mediated mRNA synthesis without affecting the half-life of the GAL4/VP-16 fusion protein. Moreover, the interaction of α-NAC/1.9.2 with a transcriptionally defective mutant of GAL4/VP-16 was severely compromised. Specific protein-protein interactions between α-NAC/1.9.2 and GAL4/VP-16 were demonstrated by gel retardation, affinity chromatography, and protein blotting assays, while interactions with TATA box-binding protein (TBP) were detected by immunoprecipitation, affinity chromatography, and protein blotting assays. Based on these interactions that define the coactivator class of proteins, we conclude that the α-NAC/1.9.2 gene product functions as a transcriptional coactivator.

ABSTRACTWe report the characterization of clone 1.9.2, a gene expressed in mineralizing osteoblasts. Remarkably, clone 1.9.2 is the murine homolog of the alpha chain of the nascent polypeptide-associated complex (a-NAC). Based on sequence similarities between a-NAC/1.9.2 and transcriptional regulatory proteins and the fact that the heterodimerization partner of a-NAC was identified as the transcription factor BTF3b (B. Wiedmann, H. Sakai, T. A. Davis, and M. Wiedmann, Nature 370:434–440, 1994), we investigated a putative role for a-NAC/1.9.2 in transcriptional control. The a-NAC/1.9.2 protein potentiated by 10-fold the activity of the chimeric activator GAL4/VP-16 in vivo. The potentiation was shown to be mediated at the level of gene transcription, because a-NAC/1.9.2 increased GAL4/VP-16-mediated mRNA synthesis without affecting the half-life of the GAL4/VP-16 fusion protein. Moreover, the interaction of a-NAC/1.9.2 with a transcriptionally defective mutant of GAL4/VP-16 was severely compromised. Specific protein-protein interactions between a-NAC/1.9.2 and GAL4/VP-16 were demonstrated by gel retardation, affinity chromatography, and protein blotting assays, while interactions with TATA box-binding protein (TBP) were detected by immunoprecipitation, affinity chromatography, and protein blotting assays. Based on these interactions that define the coactivator class of proteins, we conclude that the a-NAC/1.9.2 gene product functions as a transcriptional coactivator.

ABSTRACTThe alpha chain of the nascent polypeptide-associated complex (a-NAC) coactivator was shown to potentiate the activity of the homodimeric c-Jun activator, while transcription mediated by the c-Fos/c-Jun heterodimer was unaffected. The use of deletion mutants in pull-down assays revealed that a-NAC interacted with amino acids 1 to 89 of the c-Jun protein and that the coactivator could interact with both the unphosphorylated and the serine 73-phosphorylated form of c-Jun. N-terminal-deleted c-Jun protein failed to interact with a-NAC in mammalian two-hybrid assays, while mutant c-Jun proteins lacking the leucine zipper or the basic domain retained interaction with a-NAC in vivo. Kinetics studies with purified c-Jun homodimer and recombinant a-NAC proteins allowed determination of the mechanism of coactivation by a-NAC: the coactivator stabilized the AP-1 complex formed by the c-Jun homodimer on its DNA recognition sequence through an eightfold reduction in the dissociation constant (kd) of the complex. This effect of a-NAC was specific, because a-NAC could not stabilize the interactions of JunB or Sp1 with their cognate binding sites. Interestingly, the expression of a-NAC was first detected at 14.5 to 15 days postconception, concomitantly with the onset of ossification during embryogenesis. The a-NAC protein was specifically expressed in differentiated osteoblasts at the centers of ossification. Thus, the a-NAC gene product exhibits the properties of a developmentally regulated, bone-specific transcriptional coactivator.

•Conducted a parametric study on an electrically heated floor operated by a self-learning control system.•Considered concrete/insulation thickness, floor/air limit temperature, and fan speed as the parameters.•Proposed a trade-off Taguchi-ANOVA approach for multi-objectives: peak shifting, thermal comfort and cost saving potential.•Among all the factors, insulation thickness was found to have the highest significance.

ABSTRACTWe report a case of human immunodeficiency virus (HIV) type 1 infection not detected by a highly sensitive combined antigen-antibody assay. The virus was a subtype B strain harboring a unique sequence within the immunodominant epitope of the transmembrane glycoprotein. Immunochemical analysis indicated that this sequence was probably responsible for the failure to detect HIV antibodies.

The French Amended Finance law for 2011 provides for new rules on the taxation of trusts, mainly consisting in:

The alignment of the promoter region of several Streptomyces xylanases shows three conserved sequences which could be involved in gene regulation. By electromobility shift assays these specific sequences, present only in Streptomyces xylanolytic strains, were identified as protein-binding sites. The sequence required for efficient recognition by the retarding protein appeared to be a 4-bp inverted repeat: 5′-CTTT-Nx-AAAG-3′. The DNA-protein affinity was influenced by the culture conditions.