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Constraints on Asian and European sources of methane from Ch 4-C2H6-CO correlations in Asian outflow
Aircraft observations of Asian outflow from the Transport and Chemical Evolution Over the Pacific (TRACE-P) aircraft mission over the NW Pacific (March and April 2001) show large CH4 enhancements relative to background, as well as strong CH4-C2H 6-CO correlations that provide signatures of regional sources. We apply a global chemical transport model simulation of the CH4-C2H6-CO system for the TRACE-P period to interpret these observations in terms of CH4 sources and to explore in particular the unique constraints from the CH 4-C2H6-CO correlations. We use as a priori a global CH4 source inventory constrained with National Oceanic and Atmospheric Administration (NOAA) Climate Monitoring and Diagnostics Laboratory (CMDL) surface observations [Wang et al., 2004]. We find that the observed CH4 concentration enhancements and CH4-C2H6-CO correlations in Asian outflow in TRACE-P are deterinined mainly by anthropogenic emissions from China and Eurasia (defined here as Europe and eastern Russia), with only little contribution from tropical sources (wetlands and biomass burning). The a priori inventory overestimates the observed CH4 enhancements and shows regionally variable biases for the CH4/C2H6 slope. The CH 4/CO slopes are simulated without significant bias. Matching both the observed CH4 enhancements and the CH 4-C2H6-CO slopes in Asian outflow requires increasing the east Asian anthropogenic source of CH 4, and decreasing the Eurasian anthropogenic source, by at least 30% for both. The need to increase the east Asian source is driven by the underestimate of the CH4/C2H 6 slope in boundary layer Chinese outflow. The Streets et al. [2003] anthropogenic emission inventory for east Asia fits this constraint by increasing CH4 emissions from that region by 40% relative to the a priori, largely because of higher livestock and landfill source estimates. Eurasian sources (mostly European) then need to be reduced by 30-50% from the a priori value of 68 Tg yr -1. The decrease of European sources could result in part from recent mitigation of emissions from coal mining and landfills. Copyright 2004 by the American Geophysical Union
Experimental Investigation of Ultracapacitor Impedance Characteristics
© 2015 The Authors. Published by Elsevier Ltd. Ultracapacitors (UCs) are being increasingly studied and deployed as a short-term energy storage device in various energy systems including uninterruptible power supplies, electrified vehicles, renewable energy systems, and wireless communication. They exhibit excellent power density and energy efficiency. The dynamic behavior of a UC, however, strongly depends on its impedance characteristics. In this paper, the impedance characteristics of a commercial UC are experimentally investigated through the well-adopted Electrochemical Impedance Spectroscopy (EIS) technique. The implications of the UC operating conditions (i.e., state of charge (SOC) and temperature) to the impedance are systematically examined. The results show that the impedance is highly sensitive to temperature and SOC; and the temperature effect is more significant. The experimental design and multi-condition impedance analysis provides prudent insights into UC system integration, dimensioning, and energy management strategy synthesis in advanced energy systems
Inductive Charging Coupler with Assistive Coils
© 2016 IEEE. A wireless charging system contains a high-frequency power source, a wireless transformer/coupler, a rectifier, and the load. The wireless transformer/coupler is the key element of the wireless charging system, and the power source and the rectifier design are all dependent on its design. For a two coil type wireless transformer, the maximum efficiency is limited by the coupling coefficient, which rapidly decreases with increasing distance between the primary and secondary coils. The four coil system is widely used in low-power applications, where the maximum power transfer operating point is away from the maximum efficiency point. This paper proposes an inductive charging coupler with small assistive coils, where the high power and maximum efficiency regions overlap
Collaborative research and development (R&D) for climate technology transfer and uptake in developing countries: Towards a needs driven approach
While international cooperation to facilitate the transfer and uptake of climate technologies in developing countries is an ongoing part of climate policy conversations, international collaborative R&D has received comparatively little attention. Collaborative R&D, however, could be a potentially important contributor to facilitating the transfer and uptake of climate technologies in developing countries. But the complexities of international collaborative R&D options and their distributional consequences have been given little attention to date. This paper develops a systematic approach to informing future empirical research and policy analysis on this topic. Building on insights from relevant literature and analysis of empirical data based on a sample of existing international climate technology R&D initiatives, three contributions are made. First, the paper analyses the coverage of existing collaborative R&D efforts in relation to climate technologies, highlighting some important concerns, such as a lack of coverage of lower-income countries or adaptation technologies. Second, it provides a starting point for further systematic research and policy thinking via the development of a taxonomic approach for analysing collaborative designs. Finally, it matches characteristics of R&D collaborations against developing countries’ climate technology needs to provide policymakers with guidance on how to Configure R&D collaborations to meet these needs
Fast-dissolving core-shell composite microparticles of quercetin fabricated using a coaxial electrospray process
This study reports on novel fast-dissolving core-shell composite microparticles of quercetin fabricated using coaxial electrospraying. A PVC-coated concentric spinneret was developed to conduct the electrospray process. A series of analyses were undertaken to characterize the resultant particles in terms of their morphology, the physical form of their components, and their functional performance. Scanning and transmission electron microscopies revealed that the microparticles had spherical morphologies with clear core-shell structure visible. Differential scanning calorimetry and X-ray diffraction verified that the quercetin active ingredient in the core and sucralose and sodium dodecyl sulfate (SDS) excipients in the shell existed in the amorphous state. This is believed to be a result of second-order interactions between the components; these could be observed by Fourier transform infrared spectroscopy. In vitro dissolution and permeation studies showed that the microparticles rapidly released the incorporated quercetin within one minute, and had permeation rates across the sublingual mucosa around 10 times faster than raw quercetin
Designing crossing and selection strategies to combine diagnostic markers and quantitative traits
Designing crossing and selection strategies to combine diagnostic markers and quantitative traits
Tese de doutoramento em Biociências, ramo de especialização em Toxicologia, apresentada à Faculdade de Ciências e Tecnologia da Universidade de CoimbraDoxorubicin (DOX) is one of the most potent antineoplastic drugs. Although
possessing a superior anti-‐‑cancer activity, a broader clinical use of DOX is limited by
a dose-‐‑dependent, constant and cumulative cardiomyopathy involving deterioration
of mitochondrial function.
Although acute effects of DOX treatment often disappear when treatment finishes,
chronic effects often result in a persistent cardiotoxicity, including a progressive
deterioration of mitochondrial metabolism, the development of cardiomyopathy and
ultimately congestive heart failure. Important in the context of DOX-‐‑induced
cardiotoxicity, mitochondrial disruption has been observed in different models. This
alteration of mitochondrial function is often sub-‐‑clinical and is only manifested as
cardiomyopathy when other factors are combined, including age or different types of
cardiovascular stress. Also, metabolic alterations in the cardiac cell occur, which
contribute to the ability of the heart to withstand increased workloads. Although
mitochondrial disruption is an early and sensitive marker of DOX cardiotoxicity,
how metabolic stress contributes to the development of cardiomyopathy remains to
be determined. Because of this gap in knowledge, the objective of this work was to
use of model of metabolic inhibition in perfused hearts from saline (SAL) and DOX-‐‑
treated rats in order to identify metabolic alterations caused by an acute and sub-‐‑
chronic treatment.
Our assumption for this strategy is that a lower susceptibility to a determined
inhibitor during perfusion, would be a sign of a more robust (i.e. more capacity) of
the targeted pathway(s).
XV
For the acute treatment protocol, sixteen week-‐‑old male Wistar rats were i.p. injected
with 20mg/Kg DOX or 1mg/Kg 0.9%NaCl and sacrificed 24 hours later. For sub-‐‑
chronic protocol, eight weeks-‐‑old male Wistar rats received seven weekly s.c.
injections with DOX(2mg/Kg) or equivalent SAL solution and sacrificed one week
after the last injection. Following the protocol treatments, animals were sacrificed
and hearts were removed and perfused using a Langendorff apparatus with distinct
cardiac substrates (glucose, galactose plus glutamine -‐‑ GG or octanoate plus malate –
OM). Glycolytic (iodoacetate) and oxidative phosphorylation (rotenone-‐‑ Rot or
cyanide-‐‑ KCN) inhibitors were separately added to the different metabolic
perfusates, aiming to detect undercover mitochondrial defects in the DOX-‐‑treated
group. In non-‐‑perfused hearts, or hearts perfused in the absence (time controls, TC)
or presence of inhibitors, selected metabolic and mitochondrial proteins were semi-‐‑
quantified by Western blotting, and mRNA levels were quantified by RT-‐‑PCR.
In the acute DOX treatment model, hearts perfused with glucose as substrate
suffered a decline in the number of heart beat and rate pressure product (RPP) when
iodoacetate was added, contrarily to Rot or KCN which had no effect. With GG,
inhibitor titration decreased the heart rate, despite that the decrease in the RPP was
more evident in SAL vs. DOX group with iodoacetate and KCN. Perfusion with OM
resulted in decreased heart rate an RPP in the presence of the inhibitors, showing
equal response between treatments. When glycolytic and mitochondrial proteins
were semi-‐‑quantified by Western blotting, alterations in proteins involved in
mitochondrial biogenesis and autophagy were observed in DOX hearts perfused
with inhibitors. The data from the acute protocol study, appears to suggest that
hearts from DOX-‐‑treated animals have improved function in the presence of
XVI
metabolic inhibitors, thus indicating that DOX triggers adaptations that allow the
hearts to be less susceptible to mitochondrial and glycolytic inhibition.
In the sub-‐‑chronic model and using glucose as substrate, the DOX-‐‑treated group
showed again a better tolerability to inhibitors than SAL. With GG, titration with
iodoacetate caused a decrease in heart beat and on RPP in DOX group, when rot or
KCN was added the number of heart beat and RPP remains identical between the
two groups. Glycolytic and mitochondrial proteins semi-‐‑quantification suggested an
impairment of autophagy in DOX perfused hearts perfused, more evident during GG
perfusion. The presence of inhibitors in the perfusion also generally decreased the
total amount of proteins detected by Western Blotting, although glycolytic proteins
were increased when hearts were perfused with glucose, contrarily to GG perfusion.
The results suggest that sub-‐‑chronic DOX-‐‑treated rats suffered a metabolic
remodeling which is based on stronger glycolytic fluxes to maintain contractility,
although no overt mitochondrial defect was uncovered.
A surprising result is that regardless of the perfusion buffer used, no striking
differences between SAL and DOX hearts in terms of hemodynamic parameters were
found.
The present work suggests that metabolic remodeling during DOX acute and sub-‐‑
chronic treatment maintains cardiac function in the treated animals. This remodeling
is apparently based in a stronger contribution of glycolysis to overall metabolism.
Data from protein amount analyzed suggest that DOX treatment in both models
affect important regulators of autophagy, mitochondrial biogenesis as well as the
adenine nucleotide translocator. The results also suggest that a longer treatment
XVII
protocol or resting period should also be tested in order to uncover more profound
differences.A doxorrubicina (DOX) é um dos fármacos antineoplásicos mais potentes. Apesar de
possuir uma actividade anti-‐‑cancro superior, uma mais ampla utilização clínica da
DOX é limitada por uma dose-‐‑dependente, constante e cumulativa cardiomiopatia
que envolve a deterioração da função mitocondrial.
Embora os efeitos agudos do tratamento DOX normalmente desaparece quando se
conclui o tratamento, os efeitos crónicos resultam muitas vezes numa
cardiotoxicidade persistente, incluindo a deterioração progressiva do metabolismo
mitocondrial, o desenvolvimento de cardiomiopatia e por fim insuficiência cardíaca
congestiva. Importante no contexto da cardiotoxicidade induzida pela DOX,
perturbação mitocondrial foi observada em diferentes modelos. Esta alteração da
função mitocondrial é muitas vezes sub-‐‑clínica e só se manifesta como
cardiomiopatia quando outros factores são combinados, incluindo a idade ou
diferentes tipos de estresse cardiovascular. Além disso, ocorrem alterações
metabólicas na célula cardíaca, o que contribui para a capacidade do coração resistir
a maior demanda. Embora a perturbação mitocondrial seja um marcador precoce e
sensível de DOX cardiotoxicidade, como o stress metabólico contribui para o
desenvolvimento de cardiomiopatia permanece por determinar. Devido a essa
lacuna no conhecimento, o objetivo deste trabalho foi a utilização de um modelo de
inibição metabólica em corações perfundidos de ratos tratados com uma solução
salina (SAL) e ratos tratados com DOX, a fim de identificar alterações metabólicas
causadas por um tratamento agudo e sub-‐‑crônico.
XIX
O nosso pressuposto para esta estratégia é que uma menor susceptibilidade a um
determinado inibidor durante a perfusão, seria um sinal de uma forma mais robusta
(ou seja, mais de capacidade) da via-‐‑alvo (s).
Para o protocolo de tratamento agudo, ratos machos Wistar de 16 semanas de idade
foram injectados i.p. com 20 mg / kg de DOX ou de 1 mg / kg a 0,9% de NaCl e
sacrificados 24 horas mais tarde. Para o protocolo sub-‐‑crônico, ratos machos Wistar
de oito semanas de idade, receberam sete injecções s.c. semanais com DOX (2 mg /
kg) ou uma equivalente da solução SAL sendo sacrificados uma semana após a
última injecção. Após o protocolo de tratamentos, os animais foram sacrificados e os
corações foram perfundidos com um aparelho de Langendorff com substratos
cardíacos distintos (glucose, galactose mais glutamina -‐‑ GG ou octanoato mais
malato -‐‑ OM). Inibidores glicolíticos (iodoacetato) e inibidores da fosforilação
oxidativa (Rot-‐‑ rotenona ou KCN-‐‑ cianeto) foram adicionados separadamente nos
diferentes substratos metabólicos, com o objetivo de detectar defeitos mitocondriais
no grupo tratado com DOX. Em corações não perfundidos, ou corações perfundidos
na ausência (controlos de tempo, TC) ou na presença de inibidores, algumas
proteínas metabólicas e proteínas mitocondriais foram semi-‐‑quantificadas por
Western blotting, e os níveis de mRNA foram quantificados por RT-‐‑PCR.
No modelo de tratamento agudo DOX, corações perfundidos com glucose como
substrato sofreram um declínio no número de batimentos cardíacos e produto da
taxa de pressão (RPP), quando iodoacetato foi adicionado, ao contrário da Rot ou
KCN, que não teve nenhum efeito. Com GG, a titulação com o inibidor diminuiu a
frequência cardíaca, apesar de que a diminuição da RPP foi mais evidente no grupo
SAL vs. DOX com iodoacetato e KCN. Perfusão com OM resultou em diminuição da
XX
frequência cardíaca e do RPP na presença dos inibidores, mostrando uma resposta
igual entre os tratamentos. Quando proteínas glicolíticas e mitocondriais foram semi-‐‑
quantificadas por Western blotting, alterações de proteínas envolvidas na biogênese
mitocondrial e autofagia foram observados em corações DOX perfundidos com
inibidores. Os dados do protocolo de estudo agudo, parecem sugerir que os corações
provenientes de animais tratados com DOX na presença de inibidores, têm a função
metabólica melhorada, indicando assim que a DOX desencadeia adaptações que
permitem que os corações sejam menos susceptíveis à inibição mitocondrial e
glicolítica.
No modelo sub-‐‑crónica e utilizando glucose como substrato, o grupo tratado com
DOX mostrou novamente um melhor tolerabilidade para inibidores que SAL. Com
GG, a titulação com iodoacetato causou uma diminuição no batimento cardíaco e no
RPP em grupo DOX, quando rot ou KCN foi adicionado o número de batimentos
cardíacos e RPP permaneceram idênticos entre os dois grupos. A semi-‐‑quantificação
de proteínas glicolíticas e mitocondriais sugerem uma deficiência da autofagia em
corações DOX perfundidos, mais evidente durante a perfusão com GG. A presença
de inibidores da perfusão geralmente também reduziu a quantidade total de
proteínas detectadas através de Western Blot, embora proteínas glicolíticas
aumentaram quando os corações foram perfundidos com glucose, ao contrário da
perfusão com GG.
Os resultados sugerem que ratos tratados sub-‐‑cronicamente com DOX sofreram uma
remodelação metabólica, que é baseado em fluxos glicolíticos mais fortes para
manter a contratilidade, embora nenhum defeito mitocondrial ostensivo foi
descoberto.
XXI
Um resultado surpreendente é que, independentemente do tampão de perfusão
utilizado, não foram encontradas diferenças marcantes entre SAL e DOX corações em
termos de parâmetros hemodinâmicos.
O presente trabalho sugere que o remodelação metabólica durante o tratamento
agudo e sub-‐‑crônico com DOX, mantém a função cardíaca nos animais tratados. Esta
remodelação é, aparentemente, baseado numa contribuição mais forte da glicólise ao
metabolismo geral. Os resultados de quantidade de proteína analisados sugerem que
o tratamento com DOX em ambos os modelos afectam importantes reguladores da
autofagia e biogénese mitocondrial, bem como o translocador de nucleótidos de
adenina. Os resultados também sugerem que um protocolo de tratamento mais longo
ou com um período de repouso também devem ser testados a fim de descobrir
diferenças mais profundas
TIFA, an inflammatory signaling adaptor, is tumor suppressive for liver cancer.
TIFA (TNF receptor associated factor (TRAF)-interacting protein with a Forkhead-associated (FHA) domain), also called T2BP, was first identified using a yeast two-hybrid screening. TIFA contains a FHA domain, which directly binds phosphothreonine and phosphoserine, and a consensus TRAF6-binding motif. TIFA-mediated oligomerization and poly-ubiquitinylation of TRAF6 mediates signaling downstream of the Tumor necrosis factor alpha receptor 1 (TNFaR-I) and interleukin-1/Toll-like receptor 4 (TLR4) pathways. Examining TIFA expression in hepatocellular carcinoma (HCC) tissues microarrays, we noted marked decreases TIFA reactivity in tumor versus control samples. In agreement, we found that HCC cell lines show reduced TIFA expression levels versus normal liver controls. Reconstituting TIFA expression in HCC cell lines promoted two independent apoptosis signaling pathways: the induction of p53 and cell cycle arrest, and the activation of caspase-8 and caspase-3. In contrast, the expression of a non-oligomerizing mutant of TIFA impacted cells minimally, and suppression of TIFA expression protected cells from apoptosis. Mice bearing TIFA overexpression hepatocellular xenografts develop smaller tumors versus TIFA mutant tumors; terminal deoxynucleotidyl transferase dUTP nick end labeling staining demonstrates increased cell apoptosis, and decreased proliferation, reflecting cell cycle arrest. Interestingly, p53 has a greater role in decreased proliferation than cell death, as it appeared dispensable for TIFA-induced cell killing. The findings demonstrate a novel suppressive role of TIFA in HCC progression via promotion of cell death independent of p53
Relationships of trace gases and aerosols and the emission characteristics at Lin'an, a rural site in eastern China, during spring 2001
We present measurements of trace gases and fine aerosols obtained from a rural site in eastern China during 18 February to 30 April 2001. The field program aimed to characterize the variations in aerosol and gaseous pollutant concentrations and the emission signatures from the inland region of eastern China in the spring season. The data included O3, CO, NO, NOy*, SO2, methane, C2-C8 nonmethane hydrocarbons (NMHCs), C 1-C2 halocarbons, and the chemical composition of PM2.5. The average hourly mixing ratios (±standard deviation) of CO, SO2, and NOy* were 677 (±315) ppbv, 15.9 (±14.6) ppbv, and 13.8 (±7.2) ppbv, respectively. The mean daytime ozone mixing ratio was 41 (± 19) ppbv. The most abundant NMHC was ethane (3189 ± 717 pptv), followed by ethyne (2475 ± 1395 pptv), ethene (1679 ± 1455 pptv), and toluene (1529 ± 1608 pptv). Methyl chloride was the most abundant halocarbon (1108 ± 653 pptv). The average concentrations of particulate organic matter (POM, as organic carbon, OC, times 1.4) and elemental carbon (EC) in PM2.5 were 21.5 (±7) μg/m3 and 2.5 (±0.7) μg/m3, respectively, and sulfate and nitrate levels were 17.3 (±6.6) and 6.5 (±4) μg/m3, respectively. CO showed moderate to good correlation with NOy* (r2 = 0.59), OC (r2 = 0.65), CH3Cl (r2 = 0.59), soluble potassium (r2 = 0.53), and many NMHCs, indicating contributions from the burning of biofuel/biomass. CO also correlated with an industrial tracer, C2Cl4, indicative of some influence from industrial sources. SO2, on the other hand, correlated well with EC (r2 = 0.56), reflecting the contribution from the burning of coal. Ammonium was sufficiently abundant to fully neutralize sulfate and nitrate, indicating that there were strong emissions of ammonia from agricultural activities. Silicon and calcium had poor correlations with iron and aluminum, revealing the presence of source(s) for Si and Ca other than from soil. Examination of C2H2/CO, C3H8/C 2H6, nitrate/(nitrate + NOy* , and sulfate/(SO2 + sulfate) suggested that relatively fresh air masses had been sampled at the study site in the spring season. Comparison of the observed ratios/slopes with those derived from emission inventories showed that while the observed SO2/NO y* ratio (1.29 ppbv/ppbv) in March was comparable (within 20%) to the inventory-derived ratio for the study region, the measured CO/NOy* slope (37 ppbv/ppbv) was about 200% larger. The observed slope of CO relative to NMHC (including ethane, propane, butanes, ethene, and ethyne) also indicated the presence of excess CO, compared to the ratios from the inventories. These results strongly suggest that emissions of CO in eastern China have been underrepresented. The findings of this study highlight the importance of characterizing trace gases and aerosols within source regions of the Asian continent. The springtime results were also compared with data previously collected at the site in 1999-2000 and with those obtained on the Transport and Chemical Evolution over the Pacific (TRACE-P) aircraft and from a coastal site in South China for the same study period. Copyright 2004 by the American Geophysical Union
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