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1.
Heliyon ; 10(7): e28604, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38586417

RESUMO

The announcement of the UN Sustainable Development Goals (SDGs) provided a fresh direction to sustainability research that spans different disciplines. Consequently, scholarly databases made available the mapping of research publications to different SDGs, unleashing many opportunities for analysis. In this work, the top 100 Highly Cited Sustainability Researchers (HCSRs) and information related to them, such as the institutions they belong to, the type of these institutions, the geographical diversity of these researchers, and gender representation patterns, are analyzed. Also, from their publications, their publication pattern, including (i) the least and most researched SDGs, (ii) their Open Access publishing pattern, (iii) their collaboration pattern (iv) the pattern of their research impact, are analyzed. The most sought thematic areas of their research, top journals in which they publish, important research categories handled by these journals, etc., are also investigated. The most significant contribution of these researchers and their recent contributions are also discussed. The data indicates a significant disparity in research focus among the top 100 HCSRs, with most concentrating on "Good Health and Well Being," "Zero Hunger," and "Quality Education," while notably fewer researchers focus on "Decent Work and Economic Growth" and "No Poverty," underscoring the need for a more balanced research agenda across all SDGs. The study reveals that the United States, China, and the United Kingdom are the leading contributors to the top 100 HCSRs, suggesting that these countries are predominant in global sustainability research output, while nations like Iran and Saudi Arabia also make notable, albeit smaller, contributions. The institutional affiliations of HCSRs show a significant imbalance, with only 16 from private institutions compared to 84 from public ones. Specifically, it shows that out of the top 100 researchers, 93 are men, while only 7 are women. The analysis of authorship in publications by HCSRs reveals a tendency towards middle and last author positions, underscoring their collaborative and leadership roles within the research community. All these analyses can inform academia, industry, and policymakers about the most significant developments in research regarding SDGs.

2.
Environ Syst Decis ; 42(4): 547-555, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35646511

RESUMO

Mitigating greenhouse gas emissions is necessary to reduce the overall negative climate change impacts on crop yields and agricultural production. However, certain mitigation measures may generate unintended consequences to food availability and food access due to both land use competition and economic burden of mitigation. Integrated assessment models (IAM) are generally used to evaluate these policies; however, currently these models may not capture the importance of income and food prices for hunger and overall economic wellbeing. Here, we implement a measure of food security that captures the nutritional and economic aspects as the total expenditures on staple foods divided by income and weighted by total caloric consumption in an IAM, the global change analysis model (GCAM4.0). We then project consumer prices and our measure of food security along the shared socioeconomic pathways. Sustained economic growth underpins increases in caloric consumption and lowering expenditures on staple foods. Strict conservation policies affect food accessibility in a larger number of developing countries, whereas the negative effects of pricing terrestrial emissions are more concentrated on the poor in Sub-Saharan Africa, by substantially replacing their cropland with forests and affecting the production of key staples. Supplementary Information: The online version contains supplementary material available at 10.1007/s10669-022-09860-4.

3.
iScience ; 25(6): 104352, 2022 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-35601916

RESUMO

This study provides an empirical assessment of how adopting battery storage units can change the electricity consumption patterns of PV consumers using individual-consumer-level hourly smart meter data in Arizona, United States. We find that on average after adding batteries, PV consumers use more solar electricity to power their houses and send less solar electricity back to the grid. In addition, adding battery storage reduces electricity needed from the grid during system peak hours, helping utilities better flatten the load curves. Most importantly, we find a large degree of heterogeneity in the changes in electricity consumption patterns due to adopting battery storage that are not consistent with engineering or economic principles such as those not maximizing consumers' economic benefits. Such heterogeneous changes imply that utilities and policymakers need to further study the underlying behavioral reasons in order to maximize the social benefits of battery storage and PV co-adoption.

4.
Proc Natl Acad Sci U S A ; 118(49)2021 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-34873055

RESUMO

Endothelial dysfunction is associated with vascular disease and results in disruption of endothelial barrier function and increased sensitivity to apoptosis. Currently, there are limited treatments for improving endothelial dysfunction. Activated protein C (aPC), a promising therapeutic, signals via protease-activated receptor-1 (PAR1) and mediates several cytoprotective responses, including endothelial barrier stabilization and anti-apoptotic responses. We showed that aPC-activated PAR1 signals preferentially via ß-arrestin-2 (ß-arr2) and dishevelled-2 (Dvl2) scaffolds rather than G proteins to promote Rac1 activation and barrier protection. However, the signaling pathways utilized by aPC/PAR1 to mediate anti-apoptotic activities are not known. aPC/PAR1 cytoprotective responses also require coreceptors; however, it is not clear how coreceptors impact different aPC/PAR1 signaling pathways to drive distinct cytoprotective responses. Here, we define a ß-arr2-mediated sphingosine kinase-1 (SphK1)-sphingosine-1-phosphate receptor-1 (S1PR1)-Akt signaling axis that confers aPC/PAR1-mediated protection against cell death. Using human cultured endothelial cells, we found that endogenous PAR1 and S1PR1 coexist in caveolin-1 (Cav1)-rich microdomains and that S1PR1 coassociation with Cav1 is increased by aPC activation of PAR1. Our study further shows that aPC stimulates ß-arr2-dependent SphK1 activation independent of Dvl2 and is required for transactivation of S1PR1-Akt signaling and protection against cell death. While aPC/PAR1-induced, extracellular signal-regulated kinase 1/2 (ERK1/2) activation is also dependent on ß-arr2, neither SphK1 nor S1PR1 are integrated into the ERK1/2 pathway. Finally, aPC activation of PAR1-ß-arr2-mediated protection against apoptosis is dependent on Cav1, the principal structural protein of endothelial caveolae. These studies reveal that different aPC/PAR1 cytoprotective responses are mediated by discrete, ß-arr2-driven signaling pathways in caveolae.


Assuntos
Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo , Proteína C/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptor PAR-1/metabolismo , Receptores de Esfingosina-1-Fosfato/metabolismo , beta-Arrestina 2/metabolismo , Anilidas/farmacologia , Apoptose/fisiologia , Células Endoteliais/fisiologia , Inibidores Enzimáticos/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Compostos Heterocíclicos com 3 Anéis/farmacologia , Humanos , Lactonas/farmacologia , Metanol/farmacologia , Organofosfonatos/farmacologia , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Inibidores da Agregação Plaquetária/farmacologia , Proteína C/genética , Proteínas Proto-Oncogênicas c-akt/genética , Piridinas/farmacologia , Pirrolidinas/farmacologia , Receptor PAR-1/genética , Receptores de Esfingosina-1-Fosfato/genética , Sulfonas/farmacologia , beta-Arrestina 2/genética
5.
Mol Neurodegener ; 16(1): 51, 2021 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-34344440

RESUMO

BACKGROUND: Progranulin loss-of-function mutations are linked to frontotemporal lobar degeneration with TDP-43 positive inclusions (FTLD-TDP-Pgrn). Progranulin (PGRN) is an intracellular and secreted pro-protein that is proteolytically cleaved into individual granulin peptides, which are increasingly thought to contribute to FTLD-TDP-Pgrn disease pathophysiology. Intracellular PGRN is processed into granulins in the endo-lysosomal compartments. Therefore, to better understand the conversion of intracellular PGRN into granulins, we systematically tested the ability of different classes of endo-lysosomal proteases to process PGRN at a range of pH setpoints. RESULTS: In vitro cleavage assays identified multiple enzymes that can process human PGRN into multi- and single-granulin fragments in a pH-dependent manner. We confirmed the role of cathepsin B and cathepsin L in PGRN processing and showed that these and several previously unidentified lysosomal proteases (cathepsins E, G, K, S and V) are able to process PGRN in distinctive, pH-dependent manners. In addition, we have demonstrated a new role for asparagine endopeptidase (AEP) in processing PGRN, with AEP having the unique ability to liberate granulin F from the pro-protein. Brain tissue from individuals with FTLD-TDP-Pgrn showed increased PGRN processing to granulin F and increased AEP activity in degenerating brain regions but not in regions unaffected by disease. CONCLUSIONS: This study demonstrates that multiple lysosomal proteases may work in concert to liberate multi-granulin fragments and granulins. It also implicates both AEP and granulin F in the neurobiology of FTLD-TDP-Pgrn. Modulating progranulin cleavage and granulin production may represent therapeutic strategies for FTLD-Pgrn and other progranulin-related diseases.


Assuntos
Degeneração Lobar Frontotemporal/enzimologia , Granulinas/metabolismo , Lisossomos/enzimologia , Peptídeo Hidrolases/metabolismo , Progranulinas/metabolismo , Linhagem Celular , Humanos , Neurônios/enzimologia
6.
ACS Sens ; 6(6): 2168-2180, 2021 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-34102054

RESUMO

Lysosomes are important sites for macromolecular degradation, defined by an acidic lumenal pH of ∼4.5. To better understand lysosomal pH, we designed a novel, genetically encoded, fluorescent protein (FP)-based pH biosensor called Fluorescence Indicator REporting pH in Lysosomes (FIRE-pHLy). This biosensor was targeted to lysosomes with lysosomal-associated membrane protein 1 (LAMP1) and reported lumenal pH between 3.5 and 6.0 with monomeric teal fluorescent protein 1 (mTFP1), a bright cyan pH-sensitive FP variant with a pKa of 4.3. Ratiometric quantification was enabled with cytosolically oriented mCherry using high-content quantitative imaging. We expressed FIRE-pHLy in several cellular models and quantified the alkalinizing response to bafilomycin A1, a specific V-ATPase inhibitor. In summary, we have engineered FIRE-pHLy, a specific, robust, and versatile lysosomal pH biosensor, that has broad applications for investigating pH dynamics in aging- and lysosome-related diseases, as well as in lysosome-based drug discovery.


Assuntos
Técnicas Biossensoriais , Lisossomos , Proteínas de Fluorescência Verde , Concentração de Íons de Hidrogênio
7.
Pharmacol Rev ; 73(1): 120-151, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33268549

RESUMO

G protein-coupled receptors (GPCRs) are a large family comprising >800 signaling receptors that regulate numerous cellular and physiologic responses. GPCRs have been implicated in numerous diseases and represent the largest class of drug targets. Although advances in GPCR structure and pharmacology have improved drug discovery, the regulation of GPCR function by diverse post-translational modifications (PTMs) has received minimal attention. Over 200 PTMs are known to exist in mammalian cells, yet only a few have been reported for GPCRs. Early studies revealed phosphorylation as a major regulator of GPCR signaling, whereas later reports implicated a function for ubiquitination, glycosylation, and palmitoylation in GPCR biology. Although our knowledge of GPCR phosphorylation is extensive, our knowledge of the modifying enzymes, regulation, and function of other GPCR PTMs is limited. In this review we provide a comprehensive overview of GPCR post-translational modifications with a greater focus on new discoveries. We discuss the subcellular location and regulatory mechanisms that control post-translational modifications of GPCRs. The functional implications of newly discovered GPCR PTMs on receptor folding, biosynthesis, endocytic trafficking, dimerization, compartmentalized signaling, and biased signaling are also provided. Methods to detect and study GPCR PTMs as well as PTM crosstalk are further highlighted. Finally, we conclude with a discussion of the implications of GPCR PTMs in human disease and their importance for drug discovery. SIGNIFICANCE STATEMENT: Post-translational modification of G protein-coupled receptors (GPCRs) controls all aspects of receptor function; however, the detection and study of diverse types of GPCR modifications are limited. A thorough understanding of the role and mechanisms by which diverse post-translational modifications regulate GPCR signaling and trafficking is essential for understanding dysregulated mechanisms in disease and for improving and refining drug development for GPCRs.


Assuntos
Processamento de Proteína Pós-Traducional , Receptores Acoplados a Proteínas G , Animais , Humanos , Fosforilação , Receptores Acoplados a Proteínas G/metabolismo , Transdução de Sinais , Ubiquitinação
8.
Proc Natl Acad Sci U S A ; 117(9): 5039-5048, 2020 03 03.
Artigo em Inglês | MEDLINE | ID: mdl-32071217

RESUMO

Thrombin, a procoagulant protease, cleaves and activates protease-activated receptor-1 (PAR1) to promote inflammatory responses and endothelial dysfunction. In contrast, activated protein C (APC), an anticoagulant protease, activates PAR1 through a distinct cleavage site and promotes anti-inflammatory responses, prosurvival, and endothelial barrier stabilization. The distinct tethered ligands formed through cleavage of PAR1 by thrombin versus APC result in unique active receptor conformations that bias PAR1 signaling. Despite progress in understanding PAR1 biased signaling, the proteins and pathways utilized by thrombin versus APC signaling to induce opposing cellular functions are largely unknown. Here, we report the global phosphoproteome induced by thrombin and APC signaling in endothelial cells with the quantification of 11,266 unique phosphopeptides using multiplexed quantitative mass spectrometry. Our results reveal unique dynamic phosphoproteome profiles of thrombin and APC signaling, an enrichment of associated biological functions, including key modulators of endothelial barrier function, regulators of gene transcription, and specific kinases predicted to mediate PAR1 biased signaling. Using small interfering RNA to deplete a subset of phosphorylated proteins not previously linked to thrombin or APC signaling, a function for afadin and adducin-1 actin binding proteins in thrombin-induced endothelial barrier disruption is unveiled. Afadin depletion resulted in enhanced thrombin-promoted barrier permeability, whereas adducin-1 depletion completely ablated thrombin-induced barrier disruption without compromising p38 signaling. However, loss of adducin-1 blocked APC-induced Akt signaling. These studies define distinct thrombin and APC dynamic signaling profiles and a rich array of proteins and biological pathways that engender PAR1 biased signaling in endothelial cells.


Assuntos
Proteômica , Receptor PAR-1/metabolismo , Transdução de Sinais , Trombina/metabolismo , Proteínas de Ligação a Calmodulina , Proteínas de Transporte , Células Endoteliais/metabolismo , Humanos , Proteínas dos Microfilamentos , Fosforilação , Inibidor da Proteína C/metabolismo
9.
Ultrason Sonochem ; 62: 104891, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31796332

RESUMO

Cleaning of the flat sheet nanofiltration membranes, using backflushing, chemical cleaning, and ultrasonication operated individually as well as in combination with chemicals, has been studied in the present work. Identical hydrophilic polyamide membranes were fouled individually using an aqueous solution containing a single dye, an aqueous solution containing a mixture of dyes, and a synthetically prepared petroleum refinery effluent. Effect of different parameters such as the concentration of cleaning solution, contact time, frequency, and power of ultrasound on the efficacy of membrane cleaning has been studied. Optimal cleaning was achieved under sonication conditions of frequency of 24 kHz and power dissipation of 135 W. It was demonstrated that application of sonication under optimum conditions without chemical agents, gave about 85% water flux recovery. In the case of combined chemical and ultrasonic treatment, it was clearly observed that the use of chemical agent increased the efficacy of ultrasonic cleaning. The hybrid method recovered the initial water flux to almost 90% based on the use of 1.0 M aqueous NaOH and 4 min of sonication. Overall, the use of aqueous NaOH in combination with sonication showed a better efficiency for cleaning than the individual processes thus demonstrating a new avenue for membrane cleaning.


Assuntos
Membranas Artificiais , Nanotecnologia , Polímeros , Sonicação , Ultrafiltração/métodos , Interações Hidrofóbicas e Hidrofílicas , Microscopia Eletrônica de Varredura , Água
10.
Sci Total Environ ; 637-638: 758-770, 2018 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-29758431

RESUMO

Traditional fishing livelihoods need to adapt to changing fish catch/populations, led by numerous anthropogenic, environmental and climatic stressors. The decision to adapt can be influenced by a variety of socio-economic and perceptual factors. However, adaptation decision-making in fishing communities has rarely been studied. Based on previous literature and focus group discussions with community, this study identifies few prominent adaptation responses in marine fishing and proposes credible factors driving decisions to adopt them. Further, a household survey is conducted, and the association of these drivers with various adaptation strategies is examined among fisherfolk of Maharashtra (India). This statistical analysis is based on 601 responses collected across three regional fishing groups: urban, semi-urban and rural. Regional segregation is done to understand variability in decision-making among groups which might be having different socio-economic and perceptual attributes. The survey reveals that only few urban fishing households have been able to diversify into other livelihoods. While having economic capital increases the likelihood of adaptation among urban and semi-urban communities, rural fishermen are significantly driven by social capital. Perception of climate change affecting fish catch drives adoption of mechanized boats solely in urban region. But increasing number of extreme events affects decisions of semi-urban and rural fishermen. Further, rising pollution and trade competition is associated with adaptation responses in the urban and semi-urban community. Higher education might help fishermen choose convenient forms of adaptation. Also, cooperative membership and subsidies are critical in adaptation decisions. The framework and insights of the study suggest the importance of acknowledging differential decision-making of individuals and communities, for designing effective adaptation and capacity-building policies.


Assuntos
Pesqueiros/estatística & dados numéricos , Animais , Mudança Climática , Tomada de Decisões , Pesqueiros/economia , Pesqueiros/tendências , Humanos , Índia , População Rural
11.
Ultrason Sonochem ; 40(Pt A): 912-920, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28946503

RESUMO

The present work reports the use of ultrasonic irradiation for enhancing lipase catalyzed epoxidation of soybean oil. Higher degree of unsaturated fatty acids, present in the soybean oil was converted to epoxidized soybean oil by using an immobilized lipase, Candida antarctica (Novozym 435). The effects of various parameters on the relative percentage conversion of the double bond to oxirane oxygen were investigated and the optimum conditions were established. The parameters studied were temperature, hydrogen peroxide to ethylenic unsaturation mole ratio, stirring speed, solvent ratio, catalyst loading, ultrasound frequency, ultrasound input power and duty cycle. The main objective of this work was to intensify chemoenzymatic epoxidation of the soybean oil by using ultrasound, to reduce the time required for epoxidation. Epoxidation of the soybean oil was achieved under mild reaction conditions by indirect ultrasonic irradiations (using ultrasonic bath). The relative percentage conversion to oxirane oxygen of 91.22% was achieved within 5h. The lipase was remarkably stable under optimized reaction conditions, later was recovered and reused six times to produce epoxidized soybean oil (ESO).


Assuntos
Enzimas , Compostos de Epóxi/química , Lipase/metabolismo , Óleo de Soja/química , Ondas Ultrassônicas , Etilenos/química , Peróxido de Hidrogênio/química , Solventes/química , Temperatura
12.
Nat Commun ; 8(1): 912, 2017 10 24.
Artigo em Inglês | MEDLINE | ID: mdl-29066777

RESUMO

The UN Framework Convention on Climate Change aims to keep warming below 2 °C while recognizing developing countries' right to eradicate extreme poverty. Poverty eradication is also the first of the Sustainable Development Goals. This paper investigates potential consequences for climate targets of achieving poverty eradication. We find that eradicating extreme poverty, i.e., moving people to an income above $1.9 purchasing power parity (PPP) a day, does not jeopardize the climate target even in the absence of climate policies and with current technologies. On the other hand, bringing everybody to a still modest expenditure level of at least $2.97 PPP would have long-term consequences on achieving emission targets. Compared to the reference mitigation pathway, eradicating extreme poverty increases the effort by 2.8% whereas bringing everybody to at least $2.97 PPP would increase the required mitigation rate by 27%. Given that the top 10% global income earners are responsible for 36% of the current carbon footprint of households; the discourse should address income distribution and the carbon intensity of lifestyles.

13.
Nat Commun ; 8: 15835, 2017 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-28607494

RESUMO

Exocytic carriers convey neo-synthesized components from the Golgi apparatus to the cell surface. While the release and anterograde movement of Golgi-derived vesicles require the small GTPase RAB6, its effector ELKS promotes the targeting and docking of secretory vesicles to particular areas of the plasma membrane. Here, we show that specialized cell types exploit and divert the secretory pathway towards lysosome related organelles. In cultured melanocytes, the secretory route relies on RAB6 and ELKS to directly transport and dock Golgi-derived carriers to melanosomes. By delivering specific cargos, such as MART-1 and TYRP2/ DCT, the RAB6/ELKS-dependent secretory pathway controls the formation and maturation of melanosomes but also pigment synthesis. In addition, pigmentation defects are observed in RAB6 KO mice. Our data together reveal for the first time that the secretory pathway can be directed towards intracellular organelles of endosomal origin to ensure their biogenesis and function.


Assuntos
Lisossomos/metabolismo , Melanócitos/metabolismo , Proteínas rab de Ligação ao GTP/metabolismo , Animais , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Membrana Celular/genética , Membrana Celular/metabolismo , Endossomos/genética , Endossomos/metabolismo , Feminino , Complexo de Golgi/genética , Complexo de Golgi/metabolismo , Lisossomos/genética , Masculino , Melanossomas/genética , Melanossomas/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Transporte Proteico , Via Secretória , Proteínas rab de Ligação ao GTP/genética
15.
Proc Natl Acad Sci U S A ; 112(29): 9034-9, 2015 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-26150484

RESUMO

"Café-au-lait" macules (CALMs) and overall skin hyperpigmentation are early hallmarks of neurofibromatosis type 1 (NF1). One of the most frequent monogenic diseases, NF1 has subsequently been characterized with numerous benign Schwann cell-derived tumors. It is well established that neurofibromin, the NF1 gene product, is an antioncogene that down-regulates the RAS oncogene. In contrast, the molecular mechanisms associated with alteration of skin pigmentation have remained elusive. We have reassessed this issue by differentiating human embryonic stem cells into melanocytes. In the present study, we demonstrate that NF1 melanocytes reproduce the hyperpigmentation phenotype in vitro, and further characterize the link between loss of heterozygosity and the typical CALMs that appear over the general hyperpigmentation. Molecular mechanisms associated with these pathological phenotypes correlate with an increased activity of cAMP-mediated PKA and ERK1/2 signaling pathways, leading to overexpression of the transcription factor MITF and of the melanogenic enzymes tyrosinase and dopachrome tautomerase, all major players in melanogenesis. Finally, the hyperpigmentation phenotype can be rescued using specific inhibitors of these signaling pathways. These results open avenues for deciphering the pathological mechanisms involved in pigmentation diseases, and provide a robust assay for the development of new strategies for treating these diseases.


Assuntos
Células-Tronco Embrionárias/citologia , Hiperpigmentação/patologia , Melanócitos/patologia , Modelos Biológicos , Neurofibromatose 1/patologia , Proliferação de Células , AMP Cíclico/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Humanos , Melaninas/metabolismo , Melanócitos/enzimologia , Melanócitos/metabolismo , Melanócitos/ultraestrutura , Mutação/genética , Neurofibromina 1/genética , Fenótipo , RNA Interferente Pequeno/metabolismo , Transdução de Sinais
16.
RNA ; 18(5): 1014-28, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22450760

RESUMO

MicroRNAs control gene expression either by RNA transcript degradation or translational repression. Expressions of miRNAs are highly regulated in tissues, disruption of which leads to disease. How this regulation is achieved and maintained is still largely unknown. MiRNAs that reside on clustered or polycistronic transcripts represent a more complex case where individual miRNAs from a cluster are processed with different efficiencies despite being cotranscribed. To shed light on the regulatory mechanisms that might be operating in these cases, we considered the long polycistronic primary miRNA transcript pri-miR-17-92a that contains six miRNAs with diverse functions. The six miRNA domains on this cluster are differentially processed to produce varying amounts of resultant mature miRNAs in different tissues. How this is achieved is not known. We show, using various biochemical and biophysical methods coupled with mutational studies, that pri-miR-17-92a adopts a specific three-dimensional architecture that poses a kinetic barrier to its own processing. This tertiary structure could create suboptimal protein recognition sites on the pri-miRNA cluster due to higher-order structure formation.


Assuntos
MicroRNAs/química , MicroRNAs/metabolismo , Processamento Pós-Transcricional do RNA , Pareamento Incorreto de Bases , Sequência de Bases , Linhagem Celular , Humanos , Magnésio/química , Conformação de Ácido Nucleico , Análise de Sequência de RNA , Sequências de Repetição em Tandem
17.
J Hazard Mater ; 182(1-3): 603-10, 2010 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-20643504

RESUMO

The present study is concerned with the technique of producing a relatively small quantity of ammonia which can be used safely in a coal-fired thermal power plant to improve the efficiency of electrostatic precipitator by removing the suspended particulate material mostly fly ash, from the flue gas. In this work hydrolysis of urea has been conducted in a batch reactor at atmospheric pressure to study the different reaction variables such as reaction temperature, initial concentration and stirring speed on the conversion by using design expert software. A 2(3) full factorial central composite design (CCD) has been employed and a quadratic model equation has been developed. The study reveals that conversion increases exponentially with an increase in temperature, stirring speed and feed concentration. However the stirring speed has the greatest effect on the conversion with concentration and temperature exerting least and moderate effect respectively. The values of equilibrium conversion obtained through the developed models are found to agree well with their corresponding experimental counterparts with a satisfactory correlation coefficient of 93%. The developed quadratic model was optimized using quadratic programming to maximize conversion of urea within experimental range studied. The optimum production condition has been found to be at the temperature of 130 degrees C, feed concentration of 4.16 mol/l and stirring speed of 400 rpm and the corresponding conversion, 63.242%.


Assuntos
Amônia/química , Gases/química , Modelos Estatísticos , Ureia/química , Hidrólise , Temperatura
18.
J Hazard Mater ; 175(1-3): 629-37, 2010 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-19914776

RESUMO

With growing industrialization in power sector, air is being polluted with a host of substances-most conspicuously with suspended particulate matter emanating from coal-fired thermal power plants. Flue gas conditioning, especially in such power plants, requires in situ generation of ammonia. In the present paper, experiments for kinetic study of hydrolysis of urea have been conducted using a borosil glass reactor, first without stirring followed by with stirring. The study reveals that conversion increases exponentially with an increase in temperature and feed concentration. Furthermore, the effect of stirring speed, temperature and concentration on conversion has been studied. Using collision theory, temperature dependency of forward rate constant has been developed from which activation energy of the reaction and the frequency factors have been calculated. It has been observed that the forward rate constant increases with an increase in temperature. The activation energy and frequency factor with stirring has been found to be 59.85 kJ/mol and 3.9 x 10(6)min(-1) respectively with correlation co-efficient and standard deviation being 0.98% and +/-0.1% in that order.


Assuntos
Poluentes Atmosféricos , Amônia/química , Reatores Biológicos , Hidrólise , Ureia/química , Carvão Mineral , Desenho de Equipamento , Gases , Vidro , Cinética , Material Particulado , Centrais Elétricas , Pressão , Temperatura
19.
Proc Natl Acad Sci U S A ; 106(11): 4133-7, 2009 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-19251662

RESUMO

Article 2 of the United Nations Framework Convention on Climate Change [United Nations (1992) http://unfccc.int/resource/docs/convkp/conveng.pdf. Accessed February 9, 2009] commits signatory nations to stabilizing greenhouse gas concentrations in the atmosphere at a level that "would prevent dangerous anthropogenic interference (DAI) with the climate system." In an effort to provide some insight into impacts of climate change that might be considered DAI, authors of the Third Assessment Report (TAR) of the Intergovernmental Panel on Climate Change (IPCC) identified 5 "reasons for concern" (RFCs). Relationships between various impacts reflected in each RFC and increases in global mean temperature (GMT) were portrayed in what has come to be called the "burning embers diagram." In presenting the "embers" in the TAR, IPCC authors did not assess whether any single RFC was more important than any other; nor did they conclude what level of impacts or what atmospheric concentrations of greenhouse gases would constitute DAI, a value judgment that would be policy prescriptive. Here, we describe revisions of the sensitivities of the RFCs to increases in GMT and a more thorough understanding of the concept of vulnerability that has evolved over the past 8 years. This is based on our expert judgment about new findings in the growing literature since the publication of the TAR in 2001, including literature that was assessed in the IPCC Fourth Assessment Report (AR4), as well as additional research published since AR4. Compared with results reported in the TAR, smaller increases in GMT are now estimated to lead to significant or substantial consequences in the framework of the 5 "reasons for concern."


Assuntos
Poluição do Ar/prevenção & controle , Efeito Estufa , Cooperação Internacional , Poluição do Ar/legislação & jurisprudência , Atmosfera , Clima , Comportamento Perigoso , Previsões , Humanos , Nações Unidas
20.
Philos Trans A Math Phys Eng Sci ; 366(1881): 3769-80, 2008 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-18672450

RESUMO

Ubiquitous environments comprise resource-constrained mobile and wearable devices and computational elements embedded in everyday artefacts. These are connected to each other using both infrastructure-based as well as short-range ad hoc networks. Limited Internet connectivity limits the use of conventional security mechanisms such as public key infrastructures and other forms of server-centric authentication. Under these circumstances, peer-to-peer interactions are well suited for not just information interchange, but also managing security and privacy. However, practical solutions for protecting mobile devices, preserving privacy, evaluating trust and determining the reliability and accuracy of peer-provided data in such interactions are still in their infancy. Our research is directed towards providing stronger assurances of the reliability and trustworthiness of information and services, and the use of declarative policy-driven approaches to handle the open and dynamic nature of such systems. This paper provides an overview of some of the challenges and issues, and points out directions for progress.


Assuntos
Segurança Computacional/tendências , Internet/tendências , Privacidade , Política Pública , Software , Confiança , Estados Unidos
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