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The photophysical, photochemical and electrochemical properties of two newly synthesized ruthenium complexes, [Ru(phen)2(TAPHAT)]2+ and [Ru(phen)2(TAPHAT)Ru(phen)2]4+, are reported. We have developed a novel synthetic methodology that involves the metal-free oxidative coupling of diamino compounds to form a desired "pyrazine-type" core. This methodology is employed both on the free diamino ligand as well as on the different ruthenium complexes, therefore illustrating the applicability of this reaction. The TAPHAT ligand, which possesses 7 aromatic rings and 10 nitrogen atoms for 20 carbon atoms, gives rise to ruthenium complexes that can undergo up to three consecutive reductions centered on said ligand, a critical parameter for electron storage applications. A temperature-dependent study has confirmed the presence of a 4th MLCT state. Excited-state quenching in the presence of guanine or hydroquinone allows to foresee biomedical applications.
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A plasma-enhanced chemical vapor deposition (PECVD) process was adapted to alter the growth of multiwall carbon nanotubes (MWCNTs) so that graphene sheets grow out of their tips. Gold nanoparticle (Au-NP) decoration of graphenated MWCNTs (g-MWCNTs) was obtained by subsequent decoration by a pulsed laser deposition (PLD) process. By varying the number of laser ablation pulses (N(Lp)) in the PLD process, we were able to control the size of the gold nanoparticles and the surface coverage of the decorated g-MWCNTs. The presence of Au-NPs, preferentially located at the tip of the g-MWCNTs emitters, is shown to significantly improve the field electron emission (FEE) properties of the global g-MWCNT/Au-NP nanohybrid films. Indeed, the electric field needed to extract a current density of 0.1 µA cm(-)(2) from the g-MWCNT/Au-NP films was decreased from 2.68 V µm(-1) to a value as low as 0.96 V µm(-1). On the other hand, UV photoelectron spectroscopy (UPS) characterization revealed a decrease in the global work function of the Au-decorated g-MWCNT nanohybrids compared to that of bare g-MWCNT emitters. Surprisingly, the work function of g-MWCNT was found to decrease from 4.9 to 4.7 eV with the addition of Au-NPs-a value lower than the work function of both materials worth 5.2 and 4.9 eV for gold and g-MWCNT, respectively. Our results show that the N(Lp) dependence of the FEE characteristics of the g-MWCNT/Au-NP emitters correlates well with their work function changes. Fowler-Nordheim-theory-based calculations suggest that the significant FEE enhancement of the emitters is also caused by the Au-NPs acting as nanoscale electric field enhancers.
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Childhood acute lymphoblastic leukemia survival approaches 90%. New strategies are needed to identify the 10-15% who evade cure. We applied targeted, sequencing-based genotyping of 25 000 to 34 000 preselected potentially clinically relevant single-nucleotide polymorphisms (SNPs) to identify host genome profiles associated with relapse risk in 352 patients from the Nordic ALL92/2000 protocols and 426 patients from the German Berlin-Frankfurt-Munster (BFM) ALL2000 protocol. Patients were enrolled between 1992 and 2008 (median follow-up: 7.6 years). Eleven cross-validated SNPs were significantly associated with risk of relapse across protocols. SNP and biologic pathway level analyses associated relapse risk with leukemia aggressiveness, glucocorticosteroid pharmacology/response and drug transport/metabolism pathways. Classification and regression tree analysis identified three distinct risk groups defined by end of induction residual leukemia, white blood cell count and variants in myeloperoxidase (MPO), estrogen receptor 1 (ESR1), lamin B1 (LMNB1) and matrix metalloproteinase-7 (MMP7) genes, ATP-binding cassette transporters and glucocorticosteroid transcription regulation pathways. Relapse rates ranged from 4% (95% confidence interval (CI): 1.6-6.3%) for the best group (72% of patients) to 76% (95% CI: 41-90%) for the worst group (5% of patients, P<0.001). Validation of these findings and similar approaches to identify SNPs associated with toxicities may allow future individualized relapse and toxicity risk-based treatments adaptation.
Assuntos
Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/genética , Polimorfismo Genético , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Adolescente , Criança , Pré-Escolar , Dinamarca , Feminino , Genoma Humano , Genômica , Genótipo , Alemanha , Humanos , Lactente , Masculino , Neoplasia Residual/genética , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Resultado do TratamentoRESUMO
This work is the first detailed study concerning the multiscale electronic transport and its temperature dependence in the LiNi1/3Co1/3Mn1/3O2 (NMC) family, high-capacity electrode materials for lithium ion batteries. Powders with two different mean cluster sizes (3 µm and 10 µm) but the same particle sizes (0.4 to 1.3 µm) were measured. The detailed formula of the studied compound is Li1.04Ni(2+)0.235Ni(3+)0.09Mn(4+)0.315Co(3+)0.32O2. Different electrical relaxations are evidenced, resulting from the polarizations at the different scales of the powder architecture. When the frequency increases, three dielectric relaxations are detected in the following order due to: (a) space-charge polarization (low-frequency range) owing to the interface between the sample and the conductive metallic layer deposited on it; (b) polarization of NMC clusters (micronic scale) induced by the existence of resistive junctions between them; and (c) polarization of NMC particles (at sub-micronic scale) induced by resistive junctions between them. High interatomic level conductivity of about 20 S m(-1) was evidenced and attributed to the contribution of the extended states and to a Brownian motion of the charge carriers with mean free path similar to the lattice constant. The ratio between sample and local conductivity is more than 10(5). The large conductivity drop of 3 to 4 orders of magnitude is observed from the particle to the cluster scale. A very large number of charge carriers are blocked by the interparticle junctions within the clusters. The conductivity drop from the cluster to the sample scale is comparatively very small, owing to the dense architecture of the NMC sample in which the spherical clusters are very piled up on each other.
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We report on the KrF-laser ablation synthesis, purification and photocurrent generation properties of single-wall carbon nanotubes (SWCNTs). The thermally purified SWCNTs are integrated into hybrid photovoltaic (PV) devices by spin-coating them onto n-Si substrates. These novel SWCNTs/n-Si hybrid devices are shown to generate significant photocurrent (PC) over the entire 250-1050 nm light spectrum with external quantum efficiencies (EQE) reaching up to ~23%. Our SWCNTs/n-Si hybrid devices are not only photoactive in the traditional spectral range of Si solar cells, but generate also significant PC in the UV domain (below 400 nm). This wider spectral response is believed to be the result of PC generation from both the SWCNTs themselves and the tremendous number of local p-n junctions created at the nanotubes/Si interface. To assess the prevalence of these two contributions, the EQE spectra and J-V characteristics of these hybrid devices were investigated in both planar and top-down configurations, as a function of SWCNTs' film thickness. A sizable increase in EQE in the near UV with respect to the silicon is observed in both configurations, with a more pronounced UV photoresponse in the planar mode, confirming thereby the role of SWCNTs in the photogeneration process. The PC generation is found to reach its maximum for an optimal the SWCNT film thickness, which is shown to correspond to the best trade-off between lowest electrical resistance and highest optical transparency. Finally, by analyzing the J-V characteristics of our SWCNTs/n-Si devices with an equivalent circuit model, we were able to point out the contribution of the various electrical components involved in the photogeneration process. The SWCNTs-based devices demonstrated here open up the prospect for their use in highly effective photovoltaics and/or UV-light sensors.
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Fontes de Energia Elétrica , Lasers , Nanotubos de Carbono/química , Nanotubos de Carbono/ultraestrutura , Silício/química , Desenho de Equipamento , Análise de Falha de Equipamento , Nanotubos de Carbono/efeitos da radiação , Tamanho da Partícula , Silício/efeitos da radiação , Raios UltravioletaRESUMO
Genetic variants, including single-nucleotide polymorphisms (SNPs), are key determiners of interindividual differences in treatment efficacy and toxicity in childhood acute lymphoblastic leukemia (ALL). Although up to 13 chemotherapeutic agents are used in the treatment of this cancer, it remains a model disease for exploring the impact of genetic variation due to well-characterized cytogenetics, drug response pathways and precise monitoring of minimal residual disease. Here, we have selected clinically relevant genes and SNPs through literature screening, and on the basis of associations with key pathways, protein-protein interactions or downstream partners that have a role in drug disposition and treatment efficacy in childhood ALL. This allows exploration of pathways, where one of several genetic variants may lead to similar clinical phenotypes through related molecular mechanisms. We have designed a cost-effective, high-throughput capture assay of â¼25,000 clinically relevant SNPs, and demonstrated that multiple samples can be tagged and pooled before genome capture in targeted enrichment with a sufficient sequencing depth for genotyping. This multiplexed, targeted sequencing method allows exploration of the impact of pharmacogenetics on efficacy and toxicity in childhood ALL treatment, which will be of importance for personalized chemotherapy.
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Sequenciamento de Nucleotídeos em Larga Escala/métodos , Polimorfismo de Nucleotídeo Único , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Adolescente , Pré-Escolar , Análise Custo-Benefício , Genótipo , Sequenciamento de Nucleotídeos em Larga Escala/economia , Humanos , Lactente , Recém-Nascido , Farmacogenética , Fenótipo , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiologia , Resultado do TratamentoRESUMO
Acute type A aortic dissection is a surgical emergency. Treatment is based on dissected ascending aortic replacement and correction of an associated aortic insufficiency. Catheterization of the axillary artery, open distal anastomosis and systematic resection of the intimal tear are the main surgical evolutions of the last years. They allowed to significantly reduce intraoperative mortality rate particularly due to bleeding. Thirty days mortality rate of operated aortic dissection is about 20 to 30%. Visceral malperfusion syndromes induced by aortic dissection represent an important cause of postoperative death. An early diagnosis and treatment appears necessary. Thoracoabdominal CT scan allows understanding mechanisms inducing malperfusion. Aortography and an emergency endovascular procedure allow restoring arterial blood flow before renal or mesenteric irreversible ischemia. Collaboration between radiologist, anesthesiologist and surgeon is necessary to optimize survival of acute type A aortic dissection.
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Aneurisma da Aorta Torácica/cirurgia , Dissecção Aórtica/cirurgia , Isquemia/cirurgia , Rim/irrigação sanguínea , Mesentério/irrigação sanguínea , Reperfusão/métodos , Doença Aguda , Anastomose Cirúrgica , Dissecção Aórtica/complicações , Dissecção Aórtica/diagnóstico por imagem , Dissecção Aórtica/mortalidade , Aneurisma da Aorta Torácica/complicações , Aneurisma da Aorta Torácica/diagnóstico por imagem , Aneurisma da Aorta Torácica/mortalidade , Artéria Axilar/cirurgia , Cateterismo Periférico , Humanos , Isquemia/etiologia , Artéria Mesentérica Superior/diagnóstico por imagem , Radiografia , Análise de Sobrevida , Síndrome , Procedimentos Cirúrgicos Vasculares/métodosRESUMO
Listeria monocytogenes is a food-borne pathogen with a high mortality rate that has also emerged as a paradigm for intracellular parasitism. We present and compare the genome sequences of L. monocytogenes (2,944,528 base pairs) and a nonpathogenic species, L. innocua (3,011,209 base pairs). We found a large number of predicted genes encoding surface and secreted proteins, transporters, and transcriptional regulators, consistent with the ability of both species to adapt to diverse environments. The presence of 270 L. monocytogenes and 149 L. innocua strain-specific genes (clustered in 100 and 63 islets, respectively) suggests that virulence in Listeria results from multiple gene acquisition and deletion events.
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Proteínas de Bactérias/genética , Genoma Bacteriano , Listeria monocytogenes/genética , Listeria/genética , Adaptação Fisiológica , Motivos de Aminoácidos , Bacillus subtilis/genética , Proteínas de Bactérias/química , Proteínas de Bactérias/fisiologia , Composição de Bases , Proteínas de Transporte/química , Proteínas de Transporte/genética , Cromossomos Bacterianos/genética , DNA Bacteriano/química , DNA Bacteriano/genética , Transferência Genética Horizontal , Genes Bacterianos , Genômica , Listeria/química , Listeria/fisiologia , Listeria monocytogenes/química , Listeria monocytogenes/patogenicidade , Listeria monocytogenes/fisiologia , Proteínas de Membrana/química , Proteínas de Membrana/genética , Análise de Sequência de DNA , Staphylococcus aureus/genética , Fatores de Transcrição/química , Fatores de Transcrição/genética , Virulência/genéticaRESUMO
The aim of this study was to evaluate the prevalence rate and the risk factors for the carriage of hepatitis B markers in pregnant women in Bobo Dioulasso, Burkina Faso. Out of 917 pregnant women recruited during antenatal care, 98 (10.7%) were HBs antigen positive. Among these ones, 18.2% carded HBe antigen, 66.7% antiHBe antibodies and 95.6% antiHBc antibodies. Two risk factors were identified: maternal age of 23 and 28 (RR = 2.33, chi2 =12.21, p = 0.005) and widowage (Fisher test RR = 6.43, p = 0.0016). This high prevalence of HBs antigen calls for systematic screening for hepatitis B during antenatal care along with an immunization policy toward women of reproductive age and newborns.
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Portador Sadio/epidemiologia , Antígenos E da Hepatite B/sangue , Hepatite B/epidemiologia , Complicações Infecciosas na Gravidez/epidemiologia , Saúde da População Urbana/estatística & dados numéricos , Adolescente , Adulto , Distribuição por Idade , Biomarcadores/sangue , Burkina Faso/epidemiologia , Portador Sadio/sangue , Portador Sadio/diagnóstico , Portador Sadio/imunologia , Feminino , Necessidades e Demandas de Serviços de Saúde , Hepatite B/sangue , Hepatite B/diagnóstico , Hepatite B/imunologia , Anticorpos Anti-Hepatite B/sangue , Humanos , Programas de Rastreamento , Idade Materna , Pessoa de Meia-Idade , Vigilância da População , Gravidez , Complicações Infecciosas na Gravidez/sangue , Complicações Infecciosas na Gravidez/diagnóstico , Complicações Infecciosas na Gravidez/imunologia , Cuidado Pré-Natal , Fatores de Risco , Estudos Soroepidemiológicos , Viuvez/estatística & dados numéricosRESUMO
This study aimed to demonstrate that sufficient Ph-negative blood progenitors could be collected following administration of glycosylated rhG-CSF (lenograstim) to patients with Philadelphia chromosome (Ph)-positive chronic myeloid leukaemia (CML) who responded to recombinant alpha-interferon (alpha-IFN) (Ph-positive marrow metaphases < 35%). 23 patients received lenograstim (150 microg/m2) once daily for a median of 9 d. Peak circulating numbers of white blood cells (36.4 x 10(9)/l), CD34+ cells (24/ microl) and colony-forming unit-granulocyte-macrophage (CFU-GM; 1346.5/ml) occurred at a median of day 8, day 8 and day 7, respectively. Two to six (median three) leukaphereses (LK) were performed from days 5 to 12. The median number of mononuclear cells (MNC), CD34+ cells and CFU-GM collected per patient was 7.35 x 10(8/)kg, 2.72 x 10(6)/kg and 10.23 x 10(4)/kg, respectively. 22/23 patients had LK which contained either 10(4) CFU-GM/kg and/or 10(6) CD34+ cells/kg; 47LK (from 20/22 patients) were evaluable for cytogenetics. The median percentage of Ph-positive cells was 0, and 43/47 LK (91%) contained <35% Ph-positive cells; 25 (53%) were entirely negative. Sixteen of 20 evaluable patients had one or more LK with <35% Ph-positive cells, and 12 had at least one 100% Ph-negative LK. Mobilization and collection of Ph-negative cells were not influenced by the dose or duration of alpha-IFN administration before (or during) lenograstim administration or by the quality of cytogenetic response (complete v major) during lenograstim administration. No significant side-effects were observed. Thus, lenograstim administration can result in satisfactory Ph-negative blood progenitor cell collection. Autologous transplantation of such cells may be used when indicated.
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Adjuvantes Imunológicos/uso terapêutico , Antineoplásicos/uso terapêutico , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Interferon-alfa/uso terapêutico , Leucemia Mieloide Crônica Atípica BCR-ABL Negativa/terapia , Adulto , Feminino , Mobilização de Células-Tronco Hematopoéticas/métodos , Humanos , Lenograstim , Leucaférese/métodos , Leucemia Mieloide Crônica Atípica BCR-ABL Negativa/patologia , Masculino , Metáfase , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Proteínas Recombinantes/uso terapêuticoRESUMO
The purpose of this cooperative study was to evaluate the quantity and quality of Ph1-negative progenitor cells mobilized in the peripheral blood of patients with chronic myelogenous leukaemia soon after aplasia induced by chemotherapy. 32 patients ineligible for allografting who were cytogenetically refractory to interferon-alpha (IFN-alpha) were entered into this study. The chronic phase varied widely, with a median duration of 17 months (range 3-90 months). All patients were treated with intensive conventional chemotherapy regimens and recombinant human granulocyte colony-stimulating factor (rhuG-CSF, lenograstim). Peripheral blood progenitor cells (PBPC) were harvested by leukaphereses during early recovery from chemotherapy-induced aplasia. A total of 119 leukaphereses were performed. Median numbers of CD34+ cells and CFU-GM collected were 2.04 x 10(6)/kg and 2 9 x 10(4)/kg, respectively. There was a significant correlation between white cell count and number of CD34+ cells in the leukaphereses (P = 0.0001, r2 = 0.41, n = 104). A strict correlation between the number of CD34+ cells and CFU-GM in the leukapheretic product (P = 0.0001, r2 = 0.39, n = 110) was observed. 21% of evaluable patients (6/29) achieved a complete cytogenetic remission in the leukapheretic product and the other four patients achieved a major cytogenetic response for an overall response of 35% (10/22 patients). To date, 16 patients have been autografted and are alive. Five of them are Ph1-negative (three patients) or partially Ph1-negative (two patients). In conclusion, despite the high-risk characteristics of this study population, Ph1-negative PBPC were successfully mobilized in more than one-quarter of patients using a chemotherapy plus rhuG-CSF regimen. The importance of this achievement is increased by the current lack of other practical methods of rescuing Ph-negative cells in such patients.
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Adjuvantes Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Mobilização de Células-Tronco Hematopoéticas/métodos , Interferon-alfa/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Adolescente , Adulto , Bussulfano/administração & dosagem , Ciclofosfamida/administração & dosagem , Citarabina/administração & dosagem , Daunorrubicina/administração & dosagem , Etoposídeo/administração & dosagem , Feminino , Sobrevivência de Enxerto , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Idarubicina/administração & dosagem , Lenograstim , Leucaférese , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes/uso terapêutico , Resultado do TratamentoRESUMO
Coronary angioscopy evaluates the composition of the atherosclerotic plaque by direct examination of the arterial wall. The angioscope is fitted with a balloon which prevents assessment of the proximal segment of the vessels. The fibre optic system provides and excellent view of the mid and distal segments of the coronary arteries. The coronary arteries appear smooth and white on angioscopy. The atherosclerotic plaque is a white or yellowish incursion. Unstable plaques are characterised by the presence of thrombus. In unstable angina, thrombus is observed in 64% of cases and in 75% of cases during the first month after myocardial infarction. The colour of the plaque seems to be related to its fragility: the yellow plaque is much more common during myocardial infarction than in unstable angina (75% versus 47% of cases). Finally, after coronary angioplasty restenosis is more commonly white, covered by neo-intimal proliferation. Angioscopy has been shown to be feasible and safe and it is a better method of identifying thrombus. At present, it is a tool for clinical research in coronary thrombosis and interventional cardiology.
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Angioscopia , Doença das Coronárias/diagnóstico , Vasos Coronários , Angioplastia Coronária com Balão , Calcinose/diagnóstico , Calcinose/patologia , Angiografia Coronária , Doença das Coronárias/diagnóstico por imagem , Doença das Coronárias/terapia , Trombose Coronária/diagnóstico por imagem , Trombose Coronária/etiologia , Trombose Coronária/terapia , Humanos , Radiologia IntervencionistaRESUMO
Adrenocorticotrophin (ACTH) effects on lung development were studied in sheep. ACTH was infused into 10 fetal lambs at 129 days of gestation at a rate of 29, 110 or 250 micrograms/day for 72 h, a time course which was independent of the mechanical and hormonal forces associated with labor. Lungs were compared with those of normal fetuses at term (day 147). ACTH accelerates maturation of components of lung structure toward term values. Different components of cytodifferentiation of the type II alveolar cell showed different levels of sensitivity. The degree of acceleration, not the nature of the changes, was influenced by dose.
Assuntos
Hormônio Adrenocorticotrópico/farmacologia , Pulmão/embriologia , Glândulas Suprarrenais/anatomia & histologia , Animais , Peso Corporal/efeitos dos fármacos , Dióxido de Carbono/sangue , Relação Dose-Resposta a Droga , Feminino , Sangue Fetal/química , Hidrocortisona/análise , Concentração de Íons de Hidrogênio , Pulmão/efeitos dos fármacos , Pulmão/ultraestrutura , Medidas de Volume Pulmonar , Masculino , Troca Materno-Fetal , Microscopia Eletrônica , Tamanho do Órgão/efeitos dos fármacos , Oxigênio/sangue , Gravidez , Progesterona/sangue , Radioimunoensaio , OvinosRESUMO
The effect of fetal nephrectomy on lung development was studied in sheep. Fetal kidneys were removed early in the canalicular stage of lung development (95 to 99 days of pregnancy) and lung structure examined during the alveolar stage (125 to 134 days of gestation). Progesterone and estradiol 17 beta concentrations in maternal and fetal plasma were normal for gestational age, thus indicating that the ewes were not close to labour at the time the fetuses were removed. Mean body weight was significantly reduced in nephrectomized fetuses (P less than 0.05). Overall growth of the fetal lung was not markedly affected by fetal nephrectomy. However, compared to controls, alveolar airspaces were smaller in the cranial lobes of nephrectomized fetuses (P less than 0.05) and made up a smaller percentage of the parenchyma for the whole lung. There were fewer lamellar bodies per type 2 alveolar cell in nephrectomized fetuses (P less than 0.05), and more cells were without lamellar bodies (P less than 0.01). Umbilical venous thyroxin (T4) concentrations were lower in nephrectomized fetuses compared to control values (P less than 0.005). Plasma thyroxin concentration in nephrectomized fetuses correlated directly with thyroid weight (P less than 0.02). There was no significant difference in cortisol concentrations in maternal or fetal plasma or fetal tracheal fluid between the two groups. It is thus possible that the delayed lung development observed in nephrectomized fetuses was related to reduced thyroid activity.