Structural, mechanical and biocompatibility studies of hydroxyapatite-derived composites toughened by zirconia addition

Hydroxyapatite(OHAp)-based ceramic composites with added ZrO2 have been prepared both by sintering at 1400 °C and by hot isostatic pressing (HIP) at 1450 °C and 140 MPa pressure (argon atmosphere). The development of the crystalline phases and the microstructure of the composites have been examined using X-ray diffraction, electron microscopy, infrared and magic-angle spinning nuclear magnetic resonance (MASNMR) spectroscopic techniques. The fracture toughness and biocompatibility of the composites have also been studied. The effect of the addition of CeO2- and Y2O3-stabilized ZrO2 and of simple monoclinic ZrO2 to the initial physical mixture, on the structure and properties of the resulting composites has been investigated. In most of the sintered or HIP samples, the OHAp decomposes into tricalcium phosphate (β-TCP). CaO, which forms as a product of decomposition, dissolves completely in ZrO2 and stabilizes the latter in its cubic/tetragonal phase. Presence of the β-TCP phase in the product seems to be the result of a structural synergistic effect of hexagonal OHAp. Two structurally distinct orthophosphate groups have been identified in the composites by MASNMR of 31P and attributed to decomposition products of OHAp at higher temperatures. The composites possess high KIC values (2–3 times higher than that of pure OHAp). Decomposition of hydroxyapatite gives rise to differences in microstructure between HIP and simply sintered composites although fracture toughness values are similar in magnitude indicating the presence of several toughening mechanisms. The in vitro SP2-O cell test suggests that these composites possess good biocompatibility. The combination of good biocompatibility, desirable microstructure and easy availability of initial reactants indicates that the simply sintered composite of OHAp and monoclinic ZrO2(ZAP-30) appears to be the most suitable for prosthetic applications.

恒河猴大脑前额叶cDNA 文库的构建

为筛选出与认知、记忆相关的脑部表达基因及基因家族,利用TRIzol试剂从恒河猴大脑前额叶组织抽提总RNA,再用纯化试剂盒从总RNA中成功纯化出mRNA。按照Stratagene公司的cDNASynthesisKit(200401)、ZAP-cDNASynthesisKit(200400)和ZAP-cDNAGigapackⅢGoldCloningKit(200450)三个试剂盒的操作说明,构建了恒河猴大脑前额叶组织的cDNA文库。文库总库容为2·0×106克隆;绝大多数的cDNA插入片段≥0·5kb,平均长度≈1·0kb;cDNA片段与噬菌体载体重组率为97·3%。文库各项指标均达要求,为克隆大脑PFC区表达基因、测定基因编码区序列、揭示具有多种剪切组合模式等提供了可靠资源,也为相关基因表达调控的研究提供了方便。

实例依赖的可验证随机函数的高效构造

实例依赖的可验证随机函数是由文献[1]提出的一个新的密码学概念,它也是构造高安全性的零知识协议(如可重置零知识论证系统)的一个强有力的工具,而这些高安全性的零知识协议在智能卡和电子商务中有着重要的潜在价值。基于非交互ZAP证明系统和random oracle模型中∑OR-协议,给出了实例依赖的可验证伪随机函数的两个高效的实现和相应的安全性证明,提升了这一工具的应用价值。

The Novel Tubulin-Targeting Agent Pyrrolo-1,5-Benzoxazepine-15 Induces Apoptosis in Poor Prognostic Subgroups of Chronic Lymphocytic Leukemia

Pyrrolo-1,5-benzoxazepine-15 (PBOX-15) is a novel microtubule depolymerization agent that induces cell cycle arrest and subsequent apoptosis in a number of cancer cell lines. Chronic lymphocytic leukemia (CLL) is characterized by clonal expansion of predominately nonproliferating mature B cells. Here, we present data suggesting PBOX-15 is a potential therapeutic agent for CLL. We show activity of PBOX-15 in samples taken from a cohort of CLL patients (n = 55) representing both high-risk and low-risk disease. PBOX-15 exhibited cytotoxicity in CLL cells (n = 19) in a dose-dependent manner, with mean IC(50) of 0.55 mu mol/L. PBOX-15 significantly induced apoptosis in CLL cells (n = 46) including cells with poor prognostic markers: unmutated IgV(II) genes, CD38 and zeta-associated protein 70 (ZAP-70) expression, and fludarabine-resistant cells with chromosomal deletions in 17p. In addition, PBOX-15 was more potent than fludarabine in inducing apoptosis in fludarabine-sensitive cells. Pharmacologic inhibition and small interfering RNA knockdown of caspase-8 significantly inhibited PBOX-15-induced apoptosis. Pharmacologic inhibition of c-jun NH(2)-terminal kinase inhibited PBOX-15-induced apoptosis in mutated IgV(II) and ZAP-70(-) CLL cells but not in unmutated IgV(II) and ZAP-70(+) cells. PBOX-15 exhibited selective cytotoxicity in CLL cells compared with normal hematopoietic cells. Our data suggest that PBOX-15 represents a novel class of agents that are toxic toward both high-risk and low-risk CLL cells. The need for novel treatments is acute in CLL, especially for the subgroup of patients with poor clinical outcome and drug-resistant disease. This study identifies a novel agent with significant clinical potential.

CD38 expression level and pattern of expression remains a reliable and robust marker of progressive disease in chronic lymphocytic leukemia

Chronic lymphocytic leukemia (CLL) follows a variable clinical course which is difficult to predict at diagnosis. We assessed somatic mutation (SHM) status, CD38 and ZAP-70 expression in 87 patients (49 male, 38 female) with stage A CLL and known cytogenetic profile to compare their role in predicting disease progression, which was assessed by the treatment free interval (TFI) from diagnosis. Sixty (69%) patients were SHM+, 24 (28%) were CD38+ and ten (12%) were ZAP-70+. The median TFI for: (i) SHM + versus SHM- patients was 124 versus 26 months; hazard ratio (HR) = 3.6 [95% confidence interval (CI) = 1.8 - 7.3; P = 0.001]: (ii) CD38- versus CD38+ patients was 120 versus 34 months; HR = 2.4 (95% CI = 1.4 - 5.3; P = 0.02); and (iii) ZAP70- versus ZAP70+ was 120 versus 16 months; HR = 3.4 (95% CI = 1.4 - 8.7; P = 0.01). SHM status and CD38 retained prognostic significance on multivariate analysis whereas ZAP-70 did not. We conclude that ZAP-70 analysis does not provide additional prognostic information in this group of patients.

La protéine Nef du VIH-1 altère la fonction de Lck dans les thymocytes de souris transgéniques

La protéine Nef du VIH-1 joue un rôle important dans la pathogenèse du VIH-1 en modulant les voies de signalisation de la cellule hôte. La signalisation par le TcR est essentielle à la sélection positive pour générer les cellules simples positives (SP) CD4+ et simples positives (SP) CD8+, processus largement dépendant de l’activité de la Src kinase Lck et de son habileté à lier la queue cytoplasmique des corécepteurs CD4 et CD8. Nous avons précédemment trouvé que l’expression de Nef dans le VIH ou VIS peut induire une sévère déplétion des thymocytes et une baisse d’expression du corécepteur CD4 à la membrane. Nous avons également montré que Nef bloque la génération des thymocytes doubles positifs (DP) CD4+ CD8+ en plus d’altérer la transition des cellules DP vers CD4+ SP. Par contre, ce phénotype est récupérable par plusieurs approches dont le croisement d’une souris transgéniques exprimant Nef avec une souris exprimant la forme constitutivement active de Lck Y505F. Les résultats indiquent que la maturation des cellules CD4+ est altérée par le dysfonctionnement de la signalisation CD4-Lck. Toutefois, les mécanismes moléculaires par lesquels Nef contribue au bloc de la génération des cellules CD4+ dans le thymus demeurent très imprécis. Dans cette étude, en utilisant des approches biochimiques et de microscopie confocale, nous avons trouvé que les thymocytes transgéniques Nef+ expriment plus de Lck que les thymocytes Nef-. Malgré cette augmentation, une partie significative de Lck est incapable d’atteindre la membrane plasmique. Cette fraction était significativement accumulée dans un compartiment intracellulaire des thymocytes transgéniques exprimant Nef. Également, en utilisant la technique d’essai kinase in vitro, nous avons trouvé que l’activité kinase de Lck est significativement augmentée dans les thymocytes transgéniques mais demeure stable suite à une stimulation par un α-CD3ε + α-CD4. Également, comparativement aux thymocytes Nef-, la kinase Lck dans les thymocytes transgéniques était résistante à la dégradation suite à une stimulation. En examinant le statut de c-Cbl, le principal régulateur négatif de Lck, nous avons montré que c-Cbl colocalise faiblement avec Lck, malgré son hyperphosphorylation constitutive. Ceci pourrait expliquer l’échec de la dégradation de Lck. En plus, nous avons trouvé que suite à une stimulation par un α-CD3ε + α-CD4, la phosphorylation de Zap-70 en tyrosine 493 par Lck est diminuée, résultant d’une importante baisse de l’activité kinase de Zap-70 et d’un bloc des premiers évènements de la voie de signalisation par le TcR. Ces données indiquent que la signalisation CD4-Lck est interrompue par la présence de Nef.

Między językiem a światem. O poezji Krystyny Miłobędzkiej

Wydział Filologii Polskiej i Klasycznej: Instytut Filologii Polskiej

Critical role for an acidic amino acid region in platelet signaling by the HemITAM (hemi-immunoreceptor tyrosine-based activation motif) containing receptor CLEC-2 (C-type lectin receptor-2)

CLEC-2 is a member of new family of C-type lectin receptors characterized by a cytosolic YXXL downstream of three acidic amino acids in a sequence known as a hemITAM (hemi-immunoreceptor tyrosine-based activation motif). Dimerization of two phosphorylated CLEC-2 molecules leads to recruitment of the tyrosine kinase Syk via its tandem SH2 domains and initiation of a downstream signaling cascade. Using Syk-deficient and Zap-70-deficient cell lines we show that hemITAM signaling is restricted to Syk and that the upstream triacidic amino acid sequence is required for signaling. Using surface plasmon resonance and phosphorylation studies, we demonstrate that the triacidic amino acids are required for phosphorylation of the YXXL. These results further emphasize the distinct nature of the proximal events in signaling by hemITAM relative to ITAM receptors.

Comparative analysis of type III interferon receptor and interferon-stimulated genes

The role of a new type of interferon, known as interferon lambda, involved in anti-viral immunity was investigated. The identification of this interferon and its receptor, and their associated stimulation of the antiviral genes, Viperin and ZAP, has important implications for preventing viral infections, such as avian influenza.

Opções reais, operações urbanas e o mercado imobiliário na cidade de São Paulo

Introdução – Destaca o problema da escolha do tempo e da densidade ótimos para construir um imóvel, dadas as restrições das leis de zoneamento. Objetivo – Verificar se há um prêmio pela opção de se esperar para construir um imóvel, analisar a influência dos CEPACs no custo de construção. Métodos – O modelo amplia as inferências de Quigg (1993) e testa o modelo de Williams (1991). Os dados utilizados são da Embraesp, com 3.207 lançamentos imobiliários; da Prefeitura de São Paulo, com 259.021 imóveis; do ZAP, com 22.073 imóveis; no período de 2005 a 2011. Resultados – O valor do terreno vago baseado no modelo de opções reais excedeu o valor observado em todos os cenários, variando entre 16,6% e 61%. O maior prêmio obtido foi para imóveis comerciais (37,9%), seguido pelo prêmio para apartamentos (34,5%) e para casas (23,9%). Conclusões – Há um prêmio para se esperar para construir um imóvel. Ao se utilizar os CEPACs como instrumento para aumentar a densidade de construção, amplia-se o custo de construção do imóvel. Entretanto, a ampliação da densidade é limitada pelo aumento do custo adicional de construção.

Leucemia linfóide crônica: análise clínico-morfológica e imuno-histoquímica e correlação com fatores prognósticos clínicos

Pós-graduação em Pesquisa e Desenvolvimento (Biotecnologia Médica) - FMB

Estudo do annealing de traços de fissão em epídoto

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

O banco mundial e a política educacional brasileira: um olhar sobre o FUNDESCOLA e seu plano de desenvolvimento da escola (PDE)

Pós-graduação em Educação Escolar - FCLAR

Aprimoramento da sistemática U-Pb através do método de traços de fissão e técnicas de caracterização: termocronologia da faixa Brasília e sua correlação com a bacia do Paraná

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

β-glucan triggers spondylarthritis and Crohn's disease-like ileitis in SKG mice

The spondylarthritides (SpA), including ankylosing spondylitis (AS), psoriatic arthritis (PsA), reactive arthritis, and arthritis associated with inflammatory bowel disease, cause chronic inflammation of the large peripheral and axial joints, eyes, skin, ileum, and colon. Genetic studies reveal common candidate genes for AS, PsA, and Crohn's disease, including IL23R, IL12B, STAT3, and CARD9, all of which are associated with interleukin-23 (IL-23) signaling downstream of the dectin 1 β-glucan receptor. In autoimmune-prone SKG mice with mutated ZAP-70, which attenuates T cell receptor signaling and increases the autoreactivity of T cells in the peripheral repertoire, IL-17-dependent inflammatory arthritis developed after dectin 1-mediated fungal infection. This study was undertaken to determine whether SKG mice injected with 1,3-β-glucan (curdlan) develop evidence of SpA, and the relationship of innate and adaptive autoimmunity to this process.