The viscosity of silica fibres

The viscosity of an optical fibre over 1000 to 1150 {\deg}C is studied by inscribing an optical fibre Bragg grating that can withstand temperatures up to 1200 {\deg}C and monitoring fibre elongation under load through the Bragg wavelength shift. This optical interrogation offers high accuracy and reliability compared to direct measurements of elongation, particularly at lower temperatures, thus avoiding significant experimental error. An excellent Arrhenius fit is obtained from which an activation energy for viscous flow of Ea = 450 kJ/mol is extracted; addition of an additional temperature dependent pre-exponential does not change this value. This value is less than that idealised by some literature but consistent with other literature. The log plot of viscosity is overall found to be consistent with that reported in the literature for silica measurements on rod and beams, but substantially higher to past work reported for optical fibres. The discrepancy from an idealised activation energy Ea ~ 700 kJ/mol may be explained by noting the higher fictive temperature of the fibre. On the other hand, past optical fibre results obtained by beam bending with much lower values leave questions regarding the method of viscosity measurement and the time taken for structural equilibration. We note that because regenerated gratings already involve post-annealing to stabilise their operation at higher temperature, the structures are much more relaxed compared to normal fibres. This work highlights the need to stabilize components for operation in harsh environments before their application, despite some mechanical compromise. Given the increasing expectation of all-optical waveguide technologies operating above 1000 {\deg}C, the need to study the behaviour of glass over the long term brings added significance to the basic understanding of glass in this regime.Comment: Submitted to Acta Material

Revised Annotations, Sex-Biased Expression, and Lineage-Specific Genes in the Drosophila melanogaster group

Here, we provide revised gene models for D. ananassae, D. yakuba, and D. simulans, which include UTRs and empirically verified intron-exon boundaries, as well as ortholog groups identified using a fuzzy reciprocal-best-hit blast comparison. Using these revised annotations, we perform differential expression testing using the cufflinks suite to provide a broad overview of differential expression between reproductive tissues and the carcass. We identify thousands of genes that are differentially expressed across tissues in D. yakuba and D. simulans, with roughly 60% agreement in expression patterns of orthologs in D. yakuba and D. simulans. We identify several cases of putative polycistronic transcripts, pointing to a combination of transcriptional read-through in the genome as well as putative gene fusion and fission events across taxa. We furthermore identify hundreds of lineage specific genes in each species with no blast hits among transcripts of any other Drosophila species, which are candidates for neofunctionalized proteins and a potential source of genetic novelty.Comment: Revised manuscript, also available online preprint at G3: Genes, Genomes, Genetics. Gene models, ortholog calls, and tissue specific expression results are available at http://github.com/ThorntonLab/GFF or the UCSC browser on the Thornton Lab public track hub at http://genome.ucsc.ed

Landscape of standing variation for tandem duplications in Drosophila yakuba and Drosophila simulans

We have used whole genome paired-end Illumina sequence data to identify tandem duplications in 20 isofemale lines of D. yakuba, and 20 isofemale lines of D. simulans and performed genome wide validation with PacBio long molecule sequencing. We identify 1,415 tandem duplications that are segregating in D. yakuba as well as 975 duplications in D. simulans, indicating greater variation in D. yakuba. Additionally, we observe high rates of secondary deletions at duplicated sites, with 8% of duplicated sites in D. simulans and 17% of sites in D. yakuba modified with deletions. These secondary deletions are consistent with the action of the large loop mismatch repair system acting to remove polymorphic tandem duplication, resulting in rapid dynamics of gain and loss in duplicated alleles and a richer substrate of genetic novelty than has been previously reported. Most duplications are present in only single strains, suggesting deleterious impacts are common. D. simulans shows larger numbers of whole gene duplications in comparison to larger proportions of gene fragments in D. yakuba. D. simulans displays an excess of high frequency variants on the X chromosome, consistent with adaptive evolution through duplications on the D. simulans X or demographic forces driving duplicates to high frequency. We identify 78 chimeric genes in D. yakuba and 38 chimeric genes in D. simulans, as well as 143 cases of recruited non-coding sequence in D. yakuba and 96 in D. simulans, in agreement with rates of chimeric gene origination in D. melanogaster. Together, these results suggest that tandem duplications often result in complex variation beyond whole gene duplications that offers a rich substrate of standing variation that is likely to contribute both to detrimental phenotypes and disease, as well as to adaptive evolutionary change.Comment: Revised Version- Accepted at Molecular Biology and Evolutio

Dexamethasone Attenuates Hyperexcitability Provoked by Experimental Febrile Status Epilepticus.

The role of neuroinflammation in the mechanisms of epilepsy development is important because inflammatory mediators provide tractable targets for intervention. Inflammation is intrinsically involved in the generation of childhood febrile seizures (FSs), and prolonged FS [febrile status epilepticus (FSE)] precedes a large proportion of adult cases of temporal lobe epilepsy (TLE). As TLE is often refractory to therapy and is associated with serious cognitive and emotional problems, we investigated whether its development can be prevented using anti-inflammatory strategies. Using an immature rat model of FSE [experimental FSE (eFSE)], we administered dexamethasone (DEX), a broad anti-inflammatory agent, over 3 d following eFSE. We assessed eFSE-provoked hippocampal network hyperexcitability by quantifying the presence, frequency, and duration of hippocampal spike series, as these precede and herald the development of TLE-like epilepsy. We tested whether eFSE provoked hippocampal microgliosis, astrocytosis, and proinflammatory cytokine production in male and female rats and investigated blood-brain barrier (BBB) breaches as a potential contributor. We then evaluated whether DEX attenuated these eFSE sequelae. Spike series were not observed in control rats given vehicle or DEX, but occurred in 41.6% of eFSE-vehicle rats, associated with BBB leakage and elevated hippocampal cytokines. eFSE did not induce astrocytosis or microgliosis but provoked BBB disruption in 60% of animals. DEX significantly reduced spike series prevalence (to 7.6%) and frequency, and abrogated eFSE-induced cytokine production and BBB leakage (to 20%). These findings suggest that a short, postinsult intervention with a clinically available anti-inflammatory agent potently attenuates epilepsy-predicting hippocampal hyperexcitability, potentially by minimizing BBB disruption and related neuroinflammation

Effect of Auction Design on Bidder Entry: Evidence from An Online Labor Market

We propose that auction duration and auction description are two important auction design parameters that could serve as screening mechanisms for quality in online auctions. Using data from an online labor matching platform that connects buyers with IT service vendors, we examine the effects of auction duration and auction descriptions on auction outcomes (i.e., number of bids, bidder quality, bidding price) and project outcomes (i.e., project being contracted and being completed). Our empirical analyses show that, in buyer-determined reverse auctions of online labor matching, auctions with a longer duration and a longer description attract more bids, but they also attract more low quality bidders with less experience and lower completion rate, and hence result in a lower probability of successful contracting and completion of software service projects. Our research provides empirical evidence highlighting the strategic roles of auction design parameters like auction duration and descriptions as a potential screening mechanism for online labor matching platforms

CryoEM structure of the human SLC4A4 sodium-coupled acid-base transporter NBCe1.

Na+-coupled acid-base transporters play essential roles in human biology. Their dysfunction has been linked to cancer, heart, and brain disease. High-resolution structures of mammalian Na+-coupled acid-base transporters are not available. The sodium-bicarbonate cotransporter NBCe1 functions in multiple organs and its mutations cause blindness, abnormal growth and blood chemistry, migraines, and impaired cognitive function. Here, we have determined the structure of the membrane domain dimer of human NBCe1 at 3.9 Å resolution by cryo electron microscopy. Our atomic model and functional mutagenesis revealed the ion accessibility pathway and the ion coordination site, the latter containing residues involved in human disease-causing mutations. We identified a small number of residues within the ion coordination site whose modification transformed NBCe1 into an anion exchanger. Our data suggest that symporters and exchangers utilize comparable transport machinery and that subtle differences in their substrate-binding regions have very significant effects on their transport mode

Microscale controlled continuous cell culture

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2011.Cataloged from PDF version of thesis.Includes bibliographical references (p. 489-500).Measurements of metabolic and cellular activity through substrate and product interactions are highly dependent on environmental conditions and cellular metabolic state. For such experiments to be feasible, continuous cultures are utilized to ensure consistent conditions. However, since medium must be replenished every cell doubling time, costs can be prohibitive in large reactors. An integrated microscale bioreactor with built-in fluid metering and environmental control will enable programmed experiments capable of generating reproducible data routinely. This work develops an instrument capable of supporting automated microscale continuous culture experiments. The instrument consists of a plastic-PDMS device capable of continuous flow reactions without volume drift. A novel bonding process is invented to fabricate devices with chemically stable interfaces against water, acids, and bases. We introduce a direct CNC machining and chemical bonding fabrication process for production of fluidic devices with a 1 mL working volume, high oxygen transfer rate (kLa ~ 0.025 s-1), fast mixing (2 s), accurate flow control (± 18 nL), and closed loop control over temperature, cell density, oxygen, and pH. Providing control over environmental parameters allows the system to perform different types of cell culture on a single device, such as batch, fed-batch, chemostat, and turbidostat continuous culture. Validation experiments demonstrate that cells can be grown to high optical densities (OD = 50) and production of commercially relevant chemicals such as DNA vaccines are comparable to large scale bench fermentations. Continuous cultures are also demonstrated without contamination for 3 weeks in a single device and both steady state and dynamically controlled conditions are possible, allowing observations of cell metabolic dynamics.by Kevin Shao-Kwan Lee.Ph.D