106 research outputs found
Mesoscale Modeling and Analysis Pertinent to Electrode Processing
Fabricating devices consisting of nanoparticles is a manufacturing challenge for novel small scale devices, e.g., ultrathin porous electrodes. Techniques that can have exquisite control over the shape, size and surface properties of nanoparticles have been developed. The efficient utilization of these highly functionalized nanomaterials is dependent on the assembly behavior and resultant microstructures. Evaporation-influenced nanoparticle assembly is a promising scheme to fabricate predefined microstructures.
In the present study, a morphologically detailed mesoscale model is developed to investigate microstructure variation produced by evaporation-influenced nanoparticle aggregation. Three dynamic processes, namely solvent evaporation, nanoparticle diffusion and rotation, are incorporated in the model. Fundamentally, system dynamics is dictated by the Hamiltonian, which is the function of interparticle, particle-solvent and solvent-surroundings interactions. Irregularity in particle shape is simulated by using hexagonal particles.
Aggregation characteristics like cluster size, film thickness and nanoparticle distribution are found to be a strong function of relative strengths of interaction energies. For evaporation-induced aggregation, an appropriate evaporation rate can facilitate nanoparticle aggregation. However, very high evaporation rates lead to a highly porous structure due to fast bubble growth.
Though the usage of nanoparticles for the electrodes has become the center of research, most of the batteries are still prepared using the micro-sized active particles. A Stratification model is used to predict the distribution of micro-sized active particles and KMC method is used to predict the distribution of secondary nanoparticles like conductive additives and binders on the active particles. The stratification model predicts that at lower Peclet number, a uniform film is formed. Also at higher Sedimentation number, particles deposit at a higher rate leading to uniform film formation on the substrate.
The KMC model predictions qualitatively explain morphological properties of a nanometer sized film of particulate slurry processed at different drying temperatures. The present simulations demonstrate that the higher drying temperatures and lower chemical potentials produce more compact film with less structural and surface inhomogeneities.
This work provides guidelines for the design of efficient microstructure manufacturing strategies. In addition, the developed framework can be easily extended to study realistic slurry behaviors, e.g., polydispersed solution and morphological variations of particles
The Role of Similarity in Sound Change: Variation and Change in Diné Affricates
Studies have often documented an increase in variation and frequency of change in communities undergoing language shift. Segments that are similar across languages appear particularly vulnerable to change through phonemic transfer or subphonemic convergence with a socially-dominant language. However, phonetic documentation of specific changes in minority languages is limited, and what constitutes similarity remains vague. This paper presents a study of incipient sound changes in the Diné bizaad (Navajo) laterally-released alveolar affricates. Variation among proficient speakers points to the relevance of phonetic similarity in these changes, confirmed through acoustic analysis, while the strong correlation with age suggests external pressure, as younger speakers have less exposure to the Diné language and are more likely to substitute English clusters for Diné affricates. Overall, this study shows how multiple motivators can be identified for changes in a threatened language that otherwise appear to be straightforward substitutions from a dominant language
Mesoscale Modeling and Analysis Pertinent to Electrode Processing
Fabricating devices consisting of nanoparticles is a manufacturing challenge for novel small scale devices, e.g., ultrathin porous electrodes. Techniques that can have exquisite control over the shape, size and surface properties of nanoparticles have been developed. The efficient utilization of these highly functionalized nanomaterials is dependent on the assembly behavior and resultant microstructures. Evaporation-influenced nanoparticle assembly is a promising scheme to fabricate predefined microstructures.
In the present study, a morphologically detailed mesoscale model is developed to investigate microstructure variation produced by evaporation-influenced nanoparticle aggregation. Three dynamic processes, namely solvent evaporation, nanoparticle diffusion and rotation, are incorporated in the model. Fundamentally, system dynamics is dictated by the Hamiltonian, which is the function of interparticle, particle-solvent and solvent-surroundings interactions. Irregularity in particle shape is simulated by using hexagonal particles.
Aggregation characteristics like cluster size, film thickness and nanoparticle distribution are found to be a strong function of relative strengths of interaction energies. For evaporation-induced aggregation, an appropriate evaporation rate can facilitate nanoparticle aggregation. However, very high evaporation rates lead to a highly porous structure due to fast bubble growth.
Though the usage of nanoparticles for the electrodes has become the center of research, most of the batteries are still prepared using the micro-sized active particles. A Stratification model is used to predict the distribution of micro-sized active particles and KMC method is used to predict the distribution of secondary nanoparticles like conductive additives and binders on the active particles. The stratification model predicts that at lower Peclet number, a uniform film is formed. Also at higher Sedimentation number, particles deposit at a higher rate leading to uniform film formation on the substrate.
The KMC model predictions qualitatively explain morphological properties of a nanometer sized film of particulate slurry processed at different drying temperatures. The present simulations demonstrate that the higher drying temperatures and lower chemical potentials produce more compact film with less structural and surface inhomogeneities.
This work provides guidelines for the design of efficient microstructure manufacturing strategies. In addition, the developed framework can be easily extended to study realistic slurry behaviors, e.g., polydispersed solution and morphological variations of particles
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Many Ways to Sound Diné: Linguistic Variation in Navajo
Linguistic variation is a fundamental component of human language, and the study of how speakers and listeners ascribe subtle social meaning to linguistic variants has revealed important insights for linguistic theory. Variants also constitute the seeds of potential linguistic changes within a speech community, and patterns of the linguistic and social factors that condition contemporary variation inform what we know about the actuation and diffusion of linguistic changes. However, while sociolinguistic variation has been extensively studied in many monolingual communities speaking large global languages, it is less often studied at the same level of depth in minority languages in multilingual contexts, and relatively few studies have focused on variation and change in Native American languages. Based on interviews with participants aged 18–75, this dissertation presents an investigation of variation in contemporary Diné bizaad (Navajo), a Southern Dene (Athabaskan) language spoken by over 100,000 speakers dispersed throughout a large area in the present-day American Southwest. Through an analysis of three variable features in the speech of the fifty-one bilingual Diné bizaad-English participants, this project quantitatively analyzes the linguistic and social factors that condition variation and evaluates evidence for incipient or ongoing changes in these features. Alongside the quantitative analysis, I present a qualitative description of language attitudes and usage among these bilingual speakers. Chapters 1, 2, and 3 provide the theoretical, sociocultural, and methodological context for this study. Chapter 1 puts forth my approach to analyzing variation and change and describes how I draw on work from the fields of variationist sociolinguistics, language contact, and language documentation. Chapter 1 also includes sociohistorical background on the Diné language and people. Chapter 2 presents an overview of Diné grammar, and chapter 3 an overview of the documentation methods. Chapter 4 examines the aspiration of /th/ and /kh/, famous for their exceptionally long and variably fricated releases. Phonetic analysis indicates that the releases of /kh/ have shortened, while releases of /th/ remain long. I argue that the changes in /kh/ are motivated by phonological similarity to English [kh], while the salience of the stronger affrication of /th/, represented in some earlier descriptions as /tx/, inhibits a similar conflation, and results in a different trajectory of change. Chapter 5 presents an analysis of variation and change in the laterally-released affricates: unaspirated /t͡l ~ /kl/ and ejective /t͡ɬ’/ ~ /k͡ɬ’/. Results show evidence for two changes-in-progress, of which unaspirated /kl/ is a more recent innovation, propagated by younger speakers. In contrast, the ejective variant /k͡ɬ’/ is produced by speakers of all generations including some older speakers, even those who primarily speak Diné bizaad. These changes are motivated both by phonetic similarity and a high degree of bilingualism in the speech community. Chapter 6 investigates variation and change in the usage of the multi-functional particle nít’ę́ę́’ in discourse. The particle functions primarily as a temporal discourse sequencer, often introducing sudden or new events, and as a marker of habitual past. Overall the functions and syntactic distribution of nít’ę́ę́’ found in these stories are very similar to those recorded in earlier texts, suggesting that the development of these functions is not a new phenomenon. I discuss how an analysis of polygrammaticalization can account for the synchronic functions. Chapter 7 presents an analysis of prominent contemporary language usage, attitudes, and ideologies that emerge from discussions about linguistic variation and language practices. The results show a more advanced stage of language shift than was observed in earlier studies: Diné bizaad continues to be widely associated with Elders, family, ceremonial practices, and the Navajo Nation government, while speakers of all ages report using English as their primary communicative code. At the same time, Diné bizaad continues to be valued for its expressive and complex nature, its function as a link to Diné identity, and connection to family, especially grandparents. These results are in line with earlier studies foretelling ongoing shift, but the continuity of ideological value may prove useful in ongoing maintenance and revitalization efforts. Finally, chapter 8 summarizes the results and discusses implications for these findings
Oncogenic RAS directs silencing of tumor suppressor genes through ordered recruitment of transcriptional repressors
We previously identified 28 cofactors through which a RAS oncoprotein directs transcriptional silencing of Fas and other tumor suppressor genes (TSGs). Here we performed RNAi-based epistasis experiments and found that RAS-directed silencing occurs through a highly ordered pathway that is initiated by binding of ZFP354B, a sequence-specific DNA-binding protein, and culminates in recruitment of the DNA methyltransferase DNMT1. RNAi and pharmacological inhibition experiments reveal that silencing requires continuous function of RAS and its cofactors and can be rapidly reversed, which may have therapeutic implications for reactivation of silenced TSGs in RAS-positive cancers
Strand-specific miR-28-5p and miR-28-3p have distinct effects in colorectal cancer cells
The authors thank Sue Moreau from the Department of Scientific Publications at The University of Texas MD Anderson Cancer Center for English language editing of the manuscript. Author contributions: Study concept and design: M.I.A., P.A.Z,
G.A.C. Acquisition of data: M.I.A., L.Z., X.Z. Drafting of the manuscript: M.I.A., M.N., R.S., M.F., R.M.R., P.A.Z, G.A.C. Analysis and
interpretation of data: M.I.A., M.N., R.S., R.M., P.A.Z, G.A.C. Critical revision of the manuscript for important intellectual content: M.I.A., M.N., R.S., M.F., R.M.R., P.A.Z, G.A.C. Statistical analysis: M.I.A., C.I., L.X. Obtained funding: G.A.C. Administrative, technical, or material support: R.G., I.V., F.F., M.F., G.L. Study supervision: G.A.C. Drs Nicoloso and Spizzo are currently at the Division of
Experimental Oncology, CRO, National Cancer Institute, Aviano, ItalyBackground & Aims
MicroRNAs (miRNAs) can promote or inhibit tumor growth and are therefore being developed as targets for cancer therapies. They are diverse not only in the messenger RNAs (mRNA) they target, but in their production; the same hairpin RNA structure can generate mature products from each strand, termed 5p and 3p, that can bind different mRNAs. We analyzed the expression, functions, and mechanisms of miR-28-5p and miR-28-3p in colorectal cancer (CRC) cells.
Methods
We measured levels of miR-28-5p and miR-28-3p expression in 108 CRC and 49 normal colorectal samples (47 paired) by reverse transcription, quantitative real-time polymerase chain reaction. The roles of miR-28 in CRC development were studied using cultured HCT116, RKO, and SW480 cells and tumor xenograft analyses in immunodeficient mice; their mRNA targets were also investigated.
Results
miR-28-5p and miR-28-3p were down-regulated in CRC samples compared with normal colon samples. Overexpression of miRNAs in CRC cells had different effects and the miRNAs interacted with different mRNAs: miR-28-5p altered expression of CCND1 and HOXB3, whereas miR-28-3p bound NM23-H1. Overexpression of miR-28-5p reduced CRC cell proliferation, migration, and invasion in vitro, whereas miR-28-3p increased CRC cell migration and invasion in vitro. CRC cells overexpressing miR-28 developed tumors more slowly in mice compared with control cells, but miR-28 promoted tumor metastasis in mice.
Conclusion
miR-28-5p and miR-28-3p are transcribed from the same RNA hairpin and are down-regulated in CRC cells. Overexpression of each has different effects on CRC cell proliferation and migration. Such information has a direct application for the design of miRNA gene therapy trials.M.I.A. is supported by a PhD fellowship (SFRH/BD/47031/2008) from Fundação para a Ciência e Tecnologia, Portugal. G.A.C. is
supported as a fellow by The University of Texas MD Anderson Cancer Center Research Trust, The University of Texas System
Regents Research Scholar, and the Chronic Lymphocytic Leukemia Global Research Foundation. Work in Dr Calin’s laboratory is
supported in part by grants from the National Institutes of Health (CA135444), the US Department of Defense, the Pancreatic Cancer
Action Network (2009 Seena Magowitz AACR Pilot Grant), and the US-European Alliance for the Therapy of Chronic Lymphoid Leukemia. STR DNA fingerprinting was done by the Cancer Center Support grant
funded Characterized Cell Line core, NCI # CA16672
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Many Ways to Sound Diné: Linguistic Variation in Navajo
Linguistic variation is a fundamental component of human language, and the study of how speakers and listeners ascribe subtle social meaning to linguistic variants has revealed important insights for linguistic theory. Variants also constitute the seeds of potential linguistic changes within a speech community, and patterns of the linguistic and social factors that condition contemporary variation inform what we know about the actuation and diffusion of linguistic changes. However, while sociolinguistic variation has been extensively studied in many monolingual communities speaking large global languages, it is less often studied at the same level of depth in minority languages in multilingual contexts, and relatively few studies have focused on variation and change in Native American languages. Based on interviews with participants aged 18–75, this dissertation presents an investigation of variation in contemporary Diné bizaad (Navajo), a Southern Dene (Athabaskan) language spoken by over 100,000 speakers dispersed throughout a large area in the present-day American Southwest. Through an analysis of three variable features in the speech of the fifty-one bilingual Diné bizaad-English participants, this project quantitatively analyzes the linguistic and social factors that condition variation and evaluates evidence for incipient or ongoing changes in these features. Alongside the quantitative analysis, I present a qualitative description of language attitudes and usage among these bilingual speakers. Chapters 1, 2, and 3 provide the theoretical, sociocultural, and methodological context for this study. Chapter 1 puts forth my approach to analyzing variation and change and describes how I draw on work from the fields of variationist sociolinguistics, language contact, and language documentation. Chapter 1 also includes sociohistorical background on the Diné language and people. Chapter 2 presents an overview of Diné grammar, and chapter 3 an overview of the documentation methods. Chapter 4 examines the aspiration of /th/ and /kh/, famous for their exceptionally long and variably fricated releases. Phonetic analysis indicates that the releases of /kh/ have shortened, while releases of /th/ remain long. I argue that the changes in /kh/ are motivated by phonological similarity to English [kh], while the salience of the stronger affrication of /th/, represented in some earlier descriptions as /tx/, inhibits a similar conflation, and results in a different trajectory of change. Chapter 5 presents an analysis of variation and change in the laterally-released affricates: unaspirated /t͡l ~ /kl/ and ejective /t͡ɬ’/ ~ /k͡ɬ’/. Results show evidence for two changes-in-progress, of which unaspirated /kl/ is a more recent innovation, propagated by younger speakers. In contrast, the ejective variant /k͡ɬ’/ is produced by speakers of all generations including some older speakers, even those who primarily speak Diné bizaad. These changes are motivated both by phonetic similarity and a high degree of bilingualism in the speech community. Chapter 6 investigates variation and change in the usage of the multi-functional particle nít’ę́ę́’ in discourse. The particle functions primarily as a temporal discourse sequencer, often introducing sudden or new events, and as a marker of habitual past. Overall the functions and syntactic distribution of nít’ę́ę́’ found in these stories are very similar to those recorded in earlier texts, suggesting that the development of these functions is not a new phenomenon. I discuss how an analysis of polygrammaticalization can account for the synchronic functions. Chapter 7 presents an analysis of prominent contemporary language usage, attitudes, and ideologies that emerge from discussions about linguistic variation and language practices. The results show a more advanced stage of language shift than was observed in earlier studies: Diné bizaad continues to be widely associated with Elders, family, ceremonial practices, and the Navajo Nation government, while speakers of all ages report using English as their primary communicative code. At the same time, Diné bizaad continues to be valued for its expressive and complex nature, its function as a link to Diné identity, and connection to family, especially grandparents. These results are in line with earlier studies foretelling ongoing shift, but the continuity of ideological value may prove useful in ongoing maintenance and revitalization efforts. Finally, chapter 8 summarizes the results and discusses implications for these findings
The Changing Sounds of Exceptionally Aspirated Diné Stops
This paper presents a phonetic analysis of variation and change in the production of voiceless aspirated stops in Diné bizaad, or Navajo, a Southern Dené language spoken in the American Southwest. Diné aspirated stops are typologically famous for having exceptionally long release periods (Cho and Ladefoged 1999), and earlier studies report that the variable aspiration carries social meaning (Reichard 1945). This study revisits phonetic measures of aspiration given increasing levels of English bilingualism in the Diné speech community. Voice onset time (VOT) and spectral center of gravity (CoG) were measured in tokens of aspirated velar and alveolar stops, elicited during interviews with 51 bilingual Diné bizaad-English speakers of different ages, genders, regions, and linguistic backgrounds. Results indicate that the releases of aspirated /kh/ have shortened when compared with earlier studies, while releases of aspirated /th/ have not, likely due to the salience of their affrication rendering them perceptibly distinct from English /t/. Mixed-effects linear regression models show that region, age, and gender are significant predictors of variation and that there are ongoing changes led by women, a frequent pattern in sociolinguistics, but notable here due to its relevance in an indigenous minority language community, a rare site for variationist sociolinguistic research. Overall these findings suggest that despite encroaching language shift, Diné bizaad is not simply converging with English, and results underscore the importance of perceptual awareness in analyses of subphonemic linguistic change
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