Heterostructure Engineering of a Reverse Water Gas Shift Photocatalyst.

To achieve substantial reductions in CO2 emissions, catalysts for the photoreduction of CO2 into value-added chemicals and fuels will most likely be at the heart of key renewable-energy technologies. Despite tremendous efforts, developing highly active and selective CO2 reduction photocatalysts remains a great challenge. Herein, a metal oxide heterostructure engineering strategy that enables the gas-phase, photocatalytic, heterogeneous hydrogenation of CO2 to CO with high performance metrics (i.e., the conversion rate of CO2 to CO reached as high as 1400 µmol g cat-1 h-1) is reported. The catalyst is comprised of indium oxide nanocrystals, In2O3- x (OH) y , nucleated and grown on the surface of niobium pentoxide (Nb2O5) nanorods. The heterostructure between In2O3- x (OH) y nanocrystals and the Nb2O5 nanorod support increases the concentration of oxygen vacancies and prolongs excited state (electron and hole) lifetimes. Together, these effects result in a dramatically improved photocatalytic performance compared to the isolated In2O3- x (OH) y material. The defect optimized heterostructure exhibits a 44-fold higher conversion rate than pristine In2O3- x (OH) y . It also exhibits selective conversion of CO2 to CO as well as long-term operational stability.

A computational investigation of nickel (silicides) as potential contact layers for silicon photovoltaic cells.

Nickel has been proposed as a low-cost alternative to silver for contacting in high-performance solar cells. Nickel at a crystalline silicon surface can form a number of silicide phases, depending on fabrication conditions. Using density functional theory calculations we calculate the Schottky barrier height (SBH) at the different possible interfaces. Depending on the silicide phase, crystallographic orientation and doping the SBH at the interface with Si can range from 0.39 to 0.70 eV. These calculations demonstrate which of the nickel (silicide) phases have potential use as contacting materials for silicon based solar cells. Furthermore, we explain the origin of the SBH tuning effect of P dopant atoms as being due to a dipole formed at the interface, demonstrating the linear relationship between the charge transfer at the interface upon doping and the concomitant modulation of the SBH.

Comprehensive gene expression profiling of rat lung reveals distinct acute and chronic responses to cigarette smoke inhalation.

Chronic obstructive pulmonary disease (COPD) is a smoking-related disease that lacks effective therapies due partly to the poor understanding of disease pathogenesis. The aim of this study was to identify molecular pathways that could be responsible for the damaging consequences of smoking. To do this, we employed Gene Set Enrichment Analysis to analyze differences in global gene expression, which we then related to the pathological changes induced by cigarette smoke (CS). Sprague-Dawley rats were exposed to whole body CS for 1 day and for various periods up to 8 mo. Gene Set Enrichment Analysis of microarray data identified that metabolic processes were most significantly increased early in the response to CS. Gene sets involved in stress response and inflammation were also upregulated. CS exposure increased neutrophil chemokines, cytokines, and proteases (MMP-12) linked to the pathogenesis of COPD. After a transient acute response, the CS-exposed rats developed a distinct molecular signature after 2 wk, which was followed by the chronic phase of the response. During this phase, gene sets related to immunity and defense progressively increased and predominated at the later time points in smoke-exposed rats. Chronic CS inhalation recapitulated many of the phenotypic changes observed in COPD patients including oxidative damage to macrophages, a slowly resolving inflammation, epithelial damage, mucus hypersecretion, airway fibrosis, and emphysema. As such, it appears that metabolic pathways are central to dealing with the stress of CS exposure; however, over time, inflammation and stress response gene sets become the most significantly affected in the chronic response to CS.

Cigarette smoke disrupts VEGF165-VEGFR-2 receptor signaling complex in rat lungs and patients with COPD: morphological impact of VEGFR-2 inhibition.

VEGF is fundamental in the development and maintenance of the vasculature. VEGF(165) signaling through VEGF receptor (VEGFR)-2/kinase insert domain receptor (KDR) is a highly regulated process involving the formation of a tertiary complex with glypican (GYP)-1 and neuropilin (NRP)-1. Both VEGF and VEGFR-2 expression are reduced in emphysematous lungs; however, the mechanism of regulation of VEGF(165) signaling through the VEGFR-2 complex in response to cigarette smoke exposure in vivo, and in smokers with and without chronic obstructive pulmonary disease (COPD), is still unknown. We hypothesized that cigarette smoke exposure disrupts the VEGF(165)-VEGFR-2 complex, a potential mechanism in the pathogenesis of emphysema. We show that cigarette smoke exposure reduces NRP-1 and GYP-1 as well as VEGF and VEGFR-2 levels in rat lungs and that VEGF, VEGFR-2, GYP-1, and NRP-1 expression in the lungs of both smokers and patients with COPD are also reduced compared with nonsmokers. Moreover, our data suggest that specific inhibition of VEGFR-2 alone with NVP-AAD777 would appear not to result in emphysema in the adult rat lung. As both VEGF(165) and VEGFR-2 expression are reduced in emphysematous lungs, decreased GYP-1 and NRP-1 expression may yet further disrupt VEGF(165)-VEGFR-2 signaling. Whether or not this by itself is critical for inducing endothelial cell apoptosis and decreased vascularization of the lung seen in emphysema patients is still unclear at present. However, targeted therapies to restore VEGF(165)-VEGFR-2 complex may promote endothelial cell survival and help to ameliorate emphysema.

Characterization of cigarette smoke-induced inflammatory and mucus hypersecretory changes in rat lung and the role of CXCR2 ligands in mediating this effect.

Repetitive, acute inflammatory insults elicited by cigarette smoke (CS) contribute to the development of chronic obstructive pulmonary disease (COPD), a disorder associated with lung inflammation and mucus hypersecretion. Presently, there is a poor understanding of the acute inflammatory mechanisms involved in this process. The aims of this study were to develop an acute model to investigate temporal inflammatory changes occurring after CS exposure. Rats were exposed to whole body CS (once daily) generated from filtered research cigarettes. Initial studies indicated the generation of a neutrophilic/mucus hypersecreting lung phenotype in <4 days. Subsequent studies demonstrated that just two exposures to CS (15 h apart) elicited a robust inflammatory/mucus hypersecretory phenotype that was used to investigate mechanisms driving this response. Cytokine-induced neutrophil chemoattractants (CINCs) 1-3, the rat growth-related oncogene-alpha family homologs, and IL-1beta demonstrated time-dependent increases in lung tissue or lavage fluid over the 24-h period following CS exposure. The temporal changes in the neutrophil chemokines, CINCs 1-3, mirrored increases in neutrophil infiltration, indicative of a role in neutrophil migration. In addition, a specific CXCR2 antagonist, SB-332235, effectively inhibited CS-induced neutrophilia in a dose-dependent manner, supporting this conclusion. This modeling of the response of the rat airways to acute CS exposure indicates 1) as few as two exposures to CS will induce a phenotype with similarities to COPD and 2) a novel role for CINCs in the generation of this response. These observations represent a paradigm for the study of acute, repetitive lung insults that contribute to the development of chronic disease.

Synthesis and biological properties of novel glucocorticoid androstene C-17 furoate esters.

A series of novel corticosteroid derivatives featuring C-17 furoate ester functionality have been synthesised. Profiling in vitro and in vivo has resulted in the identification of a compound with a longer duration of action and a lower oral side effect profile in rodents compared to budesonide.

Cigarette smoke alters chromatin remodeling and induces proinflammatory genes in rat lungs.

Cigarette smoke-triggered inflammation is considered to play a central role in the development of chronic obstructive pulmonary disease by a mechanism that may involve enhanced proinflammatory gene transcription. Histone acetylation and deacetylation is a key regulator of the specificity and duration of gene transcription. Disruption in the nuclear histone acetylation:deacetylation balance (chromatin remodeling) may result in excessive transcription of specific proinflammatory genes in the lungs. In this study we show that cigarette smoke exposure results in an influx of inflammatory cells and chromatin modifications in rat lungs. This was associated with an increase in the active phosphorylated form of p38 mitogen-activated protein kinase concomitant with increased histone 3 phospho-acetylation, histone 4 acetylation, and increased DNA binding of the redox-sensitive transcription factor nuclear factor-kappaB, independent of inhibitory protein-kappaB degradation, and activator protein 1. We also observed decreased histone deacetylase 2 activity, which is due to protein modification by aldehydes and nitric oxide products present in cigarette smoke. Furthermore, we show that corticosteroid treatment has no effect on smoke-induced proinflammatory mediator release. These findings suggest a possible molecular mechanism by which cigarette smoke drives proinflammatory gene transcription and an inflammatory response in the lungs.

Uso de fósforo 31 ressonância nuclear magnética para avaliaçäo da proteçäo do miocárdio utilizando cardioplegia sanguínea contínua e normotérmica / Use of phosphorus 31 nuclear magnetic ressonance for evaluation of the myocardial protection using blood continuous and normothermic cardioplegia

Um modelo isolado de coraçao de porco perfundido com sangue foi adaptado para o uso de fósforo 31 ressonância nuclear magnética (31 pRNM) em estudos de espectroscopia do metabolismo cardíaco durante cardioplegia sangüínea contínua e normotérmica (CSCN). O experimento foi dividido em dois grupos: Grupo I (n=5): os coraçoes foram submetidos a l hora de CSCN. Grupo II (n=5): um período de 20 minutos de isquemia normotérmica durante o período de 1 hora de CSCN 17. A funçao do ventrículo esquerdo (VE) foi avaliada, com o coraçao batendo, utilizando um balao intraventricular, antes do período de parada cardioplégica e a seguir, quando o coraçao foi novamente perfundido com sangue normokalêmico. Durante todo o protocolo, análise espectroscópica do metabolismo cardíaco foi obtida utilizando-se 4.7 T/3Ocm Bruker TM Biospec 31 p RNM com uma resoluçao de 2 minutos para cada resultado. Ao final dos experimentos biopsias miocárdicas foram obtidas para anáiise de ATP e fosfocreatina (PCr) utilizando cromatografia liqüída de alta "performance" (HPLC). Nao houve perda significante de ATP e PCr durante o período de parada cardioplégica com CSCN (Grupo I). Contudo, no Grupo II, a análise espectroscópica demonstrou perda completa de PCr após 14 ñ 2 minutos durante a isquemia normotérmica acompanhada de aumento de fosfato inorgânico (Pi) e diminuiçao do pH intracelular. Quando reperfundido com CSCN, PCr, pH e Pi retomaram aos valores normais em 3 minutos. A funçao do VE avaliada através da elastância sistólica final foi mantida em l00 ñ 10 por cento dos valores obtidos antes da parada cardioplégica no Grupo I. No Grupo II, a funçao do VE foi de 88 ñ 7 por cento (p