Efficient validation and construction of border arrays

In this article we present an on-line linear time and space algorithm to check if an integer array f is the border array of at least one string w built on a bounded or unbounded size alphabet Σ. We first show some relations between the border array of some string w and the skeleton of the DFA recognizing Σ ∗ · w, independently of the explicit knowledge of w. This enables us to design algorithms for validating and generating border arrays that outperform existing ones [4, 3]. The validating algorithm lowers the delay (time spent on one element of the array) from O(|w|) to O(min{|Σ|, |w|}) comparing to algorithms in [4, 3]. Finally we give some results on the numbers of distinct border arrays on some alphabet sizes.

Etude de facteurs conditionnant l'efficacité de deux composés régulateurs de croissance, OMS 3010 (phénoxycarb) et OMS 3019 (ethoxypiridine), sur les larves du complexe Simulium damnosum (Diptera : Simuliidae)

Un criblage intensif d'insecticides régulateurs de croissance réalisé en Côte d'Ivoire sur les larves du complexe #S. Damnosum$ a permis de sélectionner deux composés agissant comme des analogues synthétiques de l'hormone juvénile : l'OMS 3010 (phénoxycarb) et l'OMS 3019 (ethoxypiridine). Toutefois leurs performances restent en dessous de celles des insecticides chimiques classiques habituellement utilisés par le programme OMS de lutte contre l'onchocercose en Afrique de l'Ouest. Outre la concentration, deux facteurs qui conditionnent leur efficacité sur les larves de simulies, ont été étudiés : le stade larvaire et le temps de contact larve/insecticide. Les résultats de cette étude ont montré que ces composés sont plus actifs sur les derniers stades larvaires (stades 6 et 7). Cependant, le temps de contact semble déterminant. Les simulies étant des espèces rhéophiles, il est difficile d'obtenir dans les conditions naturelles une exposition prolongée des larves aux produits. Les doses efficaces trop élevées, le manque d'activité suffisante pour les premiers stades larvaires et le temps de contact larve/insecticide constituent des facteurs limitants de l'utilisation opérationnelle de ce type d'insecticide dans la lutte contre les larves de simulies en Afrique de l'Ouest. (Résumé d'auteur

Activation of proteinase-activated receptor 2 in human osteoarthritic cartilage upregulates catabolic and proinflammatory pathways capable of inducing cartilage degradation: a basic science study

Proteinase-activated receptors (PARs) belong to a family of G protein-coupled receptors. PARs are activated by a serine-dependent cleavage generating a tethered activating ligand. PAR-2 was shown to be involved in inflammatory pathways. We investigated the in situ levels and modulation of PAR-2 in human normal and osteoarthritis (OA) cartilage/chondrocytes. Furthermore, we evaluated the role of PAR-2 on the synthesis of the major catabolic factors in OA cartilage, including metalloproteinase (MMP)-1 and MMP-13 and the inflammatory mediator cyclooxygenase 2 (COX-2), as well as the PAR-2-activated signalling pathways in OA chondrocytes. PAR-2 expression was determined using real-time reverse transcription-polymerase chain reaction and protein levels by immunohistochemistry in normal and OA cartilage. Protein modulation was investigated in OA cartilage explants treated with a specific PAR-2-activating peptide (PAR-2-AP), SLIGKV-NH2 (1 to 400 μM), interleukin 1 beta (IL-1β) (100 pg/mL), tumor necrosis factor-alpha (TNF-α) (5 ng/mL), transforming growth factor-beta-1 (TGF-β1) (10 ng/mL), or the signalling pathway inhibitors of p38 (SB202190), MEK1/2 (mitogen-activated protein kinase kinase) (PD98059), and nuclear factor-kappa B (NF-κB) (SN50), and PAR-2 levels were determined by immunohistochemistry. Signalling pathways were analyzed on OA chondrocytes by Western blot using specific phospho-antibodies against extracellular signal-regulated kinase 1/2 (Erk1/2), p38, JNK (c-jun N-terminal kinase), and NF-κB in the presence or absence of the PAR-2-AP and/or IL-1β. PAR-2-induced MMP and COX-2 levels in cartilage were determined by immunohistochemistry. PAR-2 is produced by human chondrocytes and is significantly upregulated in OA compared with normal chondrocytes (p < 0.04 and p < 0.03, respectively). The receptor levels were significantly upregulated by IL-1β (p < 0.006) and TNF-α (p < 0.002) as well as by the PAR-2-AP at 10, 100, and 400 μM (p < 0.02) and were downregulated by the inhibition of p38. After 48 hours of incubation, PAR-2 activation significantly induced MMP-1 and COX-2 starting at 10 μM (both p < 0.005) and MMP-13 at 100 μM (p < 0.02) as well as the phosphorylation of Erk1/2 and p38 within 5 minutes of incubation (p < 0.03). Though not statistically significant, IL-1β produced an additional effect on the activation of Erk1/2 and p38. This study documents, for the first time, functional consequences of PAR-2 activation in human OA cartilage, identifies p38 as the major signalling pathway regulating its synthesis, and demonstrates that specific PAR-2 activation induces Erk1/2 and p38 in OA chondrocytes. These results suggest PAR-2 as a potential new therapeutic target for the treatment of OA

Redbook: 1995

Advice compiled by Boston University School of Medicine students for incoming first year students and third or fourth year students preparing for clinical rotations

The shunt from the cyclooxygenase to lipoxygenase pathway in human osteoarthritic subchondral osteoblasts is linked with a variable expression of the 5-lipoxygenase-activating protein

Osteoarthritis (OA) is characterized by articular cartilage degradation and hypertrophic bone changes with osteophyte formation and abnormal bone remodeling. Two groups of OA patients were identified via the production of variable and opposite levels of prostaglandin E(2 )(PGE(2)) or leukotriene B(4 )(LTB(4)) by subchondral osteoblasts, PGE(2 )levels discriminating between low and high subgroups. We studied whether the expression of 5-lipoxygenase (5-LO) or 5-LO-activating protein (FLAP) is responsible for the shunt from prostaglandins to leukotrienes. FLAP mRNA levels varied in low and high OA groups compared with normal, whereas mRNA levels of 5-LO were similar in all osteoblasts. Selective inhibition of cyclooxygenase-2 (COX-2) with NS-398-stimulated FLAP expression in the high OA osteoblasts subgroup, whereas it was without effect in the low OA osteoblasts subgroup. The addition of PGE(2 )to the low OA osteoblasts subgroup decreased FLAP expression but failed to affect it in the high OA osteoblasts subgroup. LTB(4 )levels in OA osteoblasts were stimulated about twofold by 1,25-dihydroxyvitamin D(3 )(1,25(OH)(2)D(3)) plus transforming growth factor-β (TGF-β), a situation corresponding to their effect on FLAP mRNA levels. Treatments with 1,25(OH)(2)D(3 )and TGF-β also modulated PGE(2 )production. TGF-β stimulated PGE(2 )production in both OA osteoblast groups, whereas 1,25(OH)(2)D(3 )alone had a limited effect but decreased the effect of TGF-β in the low OA osteoblasts subgroup. This modulation of PGE(2 )production was mirrored by the synthesis of COX-2. IL-18 levels were only slightly increased in a subgroup of OA osteoblasts compared with normal; however, no relationship was observed overall between IL-18 and PGE(2 )levels in normal and OA osteoblasts. These results suggest that the shunt from the production of PGE(2 )to LTB(4 )is through regulation of the expression of FLAP, not 5-LO, in OA osteoblasts. The expression of FLAP in OA osteoblasts is also modulated differently by 1,25(OH)(2)D(3 )and TGF-β depending on their endogenous low and high PGE(2 )levels