Doctor of Philosophy

dissertationThis work is a study of the optical properties of single-wall carbon nanotubes (SWNTs) using continuous wave (CW) modulation spectroscopy and resonant Raman scattering. SWNTs comprise a nanoscale, quasi-1D system in which the electrons are strongly interacting, resulting in the photo-generation of excitons. Our optical studies have revealed the behavior of these excitons under a number of di fferent perturbations to the system. We have used absorption, reflectance, electro-absorption (EA), photo-induced absorption (PA), charge-induced absorption (CIA), and resonant Raman scattering (RRS) on films of SWNTs. Our EA results provide strong evidence for the dominance of excitons in the optical absorption spectra of SWNT films. The absence of Franz-Keldysh oscillations and the presence of a derivative-like structure of the EA spectra indicate that the oscillator strength goes to the generation of excitons and not to interband electronic transitions. Furthermore, some of the photo-generated excitons are long-lived due to charge trapping in individual tubes within bundles, and this leads to a PA spectrum that is extraordinarily similar to the EA signal. When SWNTs are electrochemically doped we see that the exciton absorption is bleached due to k-space fi lling and screening of the excitons by the modi ed local dielectric, while there is very little shift in the exciton transition energies due to band-gap renormalization. Simultaneously the infrared absorption, which is due to Drude free-carriers absorption, is enhanced. A similar behavior is observed in the case of direct charge injection. The RRS of doped SWNT samples shows a frequency shift of many of the Raman-active modes that is commensurate with the macroscopic actuation observed in nanotube-based electrochemical devices. This indicates that doping-induced changes in the lattice are connected with softening and sti ening of the vibrational modes. Our results impact many proposed technologies that exploit the unique prop-erties of SWNTs. Displays, batteries, and even photovoltaics that incorporate nanotubes are already in development. The performance and robustness of these devices could be improved when our results are taken into account

The effects of charge injection in single-wall carbon nanotubes studied by charge-induced absorption

Journal ArticleWe studied direct charge injection in a heterogeneous film of single-wall carbon nanotubes using the technique of charge-induced absorption. We found that the injected charges screen the excitons in the semiconducting tubes, reducing their binding energy and transferring oscillator strength from the exciton transitions to free carriers. These effects parallel those of the electrochemical doping in the same samples

Genomic surveillance of SARS-CoV-2 using long-range PCR primers

IntroductionWhole Genome Sequencing (WGS) of the SARS-CoV-2 virus is crucial in the surveillance of the COVID-19 pandemic. Several primer schemes have been developed to sequence nearly all of the ~30,000 nucleotide SARS-CoV-2 genome, using a multiplex PCR approach to amplify cDNA copies of the viral genomic RNA. Midnight primers and ARTIC V4.1 primers are the most popular primer schemes that can amplify segments of SARS-CoV-2 (400 bp and 1200 bp, respectively) tiled across the viral RNA genome. Mutations within primer binding sites and primer-primer interactions can result in amplicon dropouts and coverage bias, yielding low-quality genomes with ‘Ns’ inserted in the missing amplicon regions, causing inaccurate lineage assignments, and making it challenging to monitor lineage-specific mutations in Variants of Concern (VoCs).MethodsIn this study we used a set of seven long-range PCR primer pairs to sequence clinical isolates of SARS-CoV-2 on Oxford Nanopore sequencer. These long-range primers generate seven amplicons approximately 4500 bp that covered whole genome of SARS-CoV-2. One of these regions includes the full-length S-gene by using a set of flanking primers. We also evaluated the performance of these long-range primers with Midnight primers by sequencing 94 clinical isolates in a Nanopore flow cell.Results and discussionUsing a small set of long-range primers to sequence SARS-CoV-2 genomes reduces the possibility of amplicon dropout and coverage bias. The key finding of this study is that long range primers can be used in single-molecule sequencing of RNA viruses in surveillance of emerging variants. We also show that by designing primers flanking the S-gene, we can obtain reliable identification of SARS-CoV-2 variants

Accurate Crystal Structure Prediction of New 2D Hybrid Organic Inorganic Perovskites

Low dimensional hybrid organic-inorganic perovskites (HOIPs) represent a promising class of electronically active materials for both light absorption and emission. The design space of HOIPs is extremely large, since a diverse space of organic cations can be combined with different inorganic frameworks. This immense design space allows for tunable electronic and mechanical properties, but also necessitates the development of new tools for in silico high throughput analysis of candidate structures. In this work, we present an accurate, efficient, transferable and widely applicable machine learning interatomic potential (MLIP) for predicting the structure of new 2D HOIPs. Using the MACE architecture, an MLIP is trained on 86 diverse experimentally reported HOIP structures. The model is tested on 73 unseen perovskite compositions, and achieves chemical accuracy with respect to the reference electronic structure method. Our model is then combined with a simple random structure search algorithm to predict the structure of hypothetical HOIPs given only the proposed composition. Success is demonstrated by correctly and reliably recovering the crystal structure of a set of experimentally known 2D perovskites. Such a random structure search is impossible with ab initio methods due to the associated computational cost, but is relatively inexpensive with the MACE potential. Finally, the procedure is used to predict the structure formed by a new organic cation with no previously known corresponding perovskite. Laboratory synthesis of the new hybrid perovskite confirms the accuracy of our prediction. This capability, applied at scale, enables efficient screening of thousands of combinations of organic cations and inorganic layers.Comment: 14 pages and 9 figures in the main text. Supplementary included in pd

Recombination and its impact on the genome of the haplodiploid parasitoid wasp Nasonia

Homologous meiotic recombination occurs in most sexually reproducing organisms, yet its evolutionary advantages are elusive. Previous research explored recombination in the honeybee, a eusocial hymenopteran with an exceptionally high genome-wide recombination rate. A comparable study in a non-social member of the Hymenoptera that would disentangle the impact of sociality from Hymenoptera-specific features such as haplodiploidy on the evolution of the high genome-wide recombination rate in social Hymenoptera is missing. Utilizing single-nucleotide polymorphisms (SNPs) between two Nasonia parasitoid wasp genomes, we developed a SNP genotyping microarray to infer a high-density linkage map for Nasonia. The map comprises 1,255 markers with an average distance of 0.3 cM. The mapped markers enabled us to arrange 265 scaffolds of the Nasonia genome assembly 1.0 on the linkage map, representing 63.6% of the assembled N. vitripennis genome. We estimated a genome-wide recombination rate of 1.4-1.5 cM/Mb for Nasonia, which is less than one tenth of the rate reported for the honeybee. The local recombination rate in Nasonia is positively correlated with the distance to the center of the linkage groups, GC content, and the proportion of simple repeats. In contrast to the honeybee genome, gene density in the parasitoid wasp genome is positively associated with the recombination rate; regions of low recombination are characterized by fewer genes with larger introns and by a greater distance between genes. Finally, we found that genes in regions of the genome with a low recombination frequency tend to have a higher ratio of non-synonymous to synonymous substitutions, likely due to the accumulation of slightly deleterious non-synonymous substitutions. These findings are consistent with the hypothesis that recombination reduces interference between linked sites and thereby facilitates adaptive evolution and the purging of deleterious mutations. Our results imply that the genomes of haplodiploid and of diploid higher eukaryotes do not differ systematically in their recombination rates and associated parameters.Publisher PDFPeer reviewe

On Machine-Learned Classification of Variable Stars with Sparse and Noisy Time-Series Data

With the coming data deluge from synoptic surveys, there is a growing need for frameworks that can quickly and automatically produce calibrated classification probabilities for newly-observed variables based on a small number of time-series measurements. In this paper, we introduce a methodology for variable-star classification, drawing from modern machine-learning techniques. We describe how to homogenize the information gleaned from light curves by selection and computation of real-numbered metrics ("feature"), detail methods to robustly estimate periodic light-curve features, introduce tree-ensemble methods for accurate variable star classification, and show how to rigorously evaluate the classification results using cross validation. On a 25-class data set of 1542 well-studied variable stars, we achieve a 22.8% overall classification error using the random forest classifier; this represents a 24% improvement over the best previous classifier on these data. This methodology is effective for identifying samples of specific science classes: for pulsational variables used in Milky Way tomography we obtain a discovery efficiency of 98.2% and for eclipsing systems we find an efficiency of 99.1%, both at 95% purity. We show that the random forest (RF) classifier is superior to other machine-learned methods in terms of accuracy, speed, and relative immunity to features with no useful class information; the RF classifier can also be used to estimate the importance of each feature in classification. Additionally, we present the first astronomical use of hierarchical classification methods to incorporate a known class taxonomy in the classifier, which further reduces the catastrophic error rate to 7.8%. Excluding low-amplitude sources, our overall error rate improves to 14%, with a catastrophic error rate of 3.5%.Comment: 23 pages, 9 figure

Thrombolytic removal of intraventricular haemorrhage in treatment of severe stroke: results of the randomised, multicentre, multiregion, placebo-controlled CLEAR III trial

Background: Intraventricular haemorrhage is a subtype of intracerebral haemorrhage, with 50% mortality and serious disability for survivors. We aimed to test whether attempting to remove intraventricular haemorrhage with alteplase versus saline irrigation improved functional outcome. Methods: In this randomised, double-blinded, placebo-controlled, multiregional trial (CLEAR III), participants with a routinely placed extraventricular drain, in the intensive care unit with stable, non-traumatic intracerebral haemorrhage volume less than 30 mL, intraventricular haemorrhage obstructing the 3rd or 4th ventricles, and no underlying pathology were adaptively randomly assigned (1:1), via a web-based system to receive up to 12 doses, 8 h apart of 1 mg of alteplase or 0·9% saline via the extraventricular drain. The treating physician, clinical research staff, and participants were masked to treatment assignment. CT scans were obtained every 24 h throughout dosing. The primary efficacy outcome was good functional outcome, defined as a modified Rankin Scale score (mRS) of 3 or less at 180 days per central adjudication by blinded evaluators. This study is registered with ClinicalTrials.gov, NCT00784134. Findings: Between Sept 18, 2009, and Jan 13, 2015, 500 patients were randomised: 249 to the alteplase group and 251 to the saline group. 180-day follow-up data were available for analysis from 246 of 249 participants in the alteplase group and 245 of 251 participants in the placebo group. The primary efficacy outcome was similar in each group (good outcome in alteplase group 48% vs saline 45%; risk ratio [RR] 1·06 [95% CI 0·88–1·28; p=0·554]). A difference of 3·5% (RR 1·08 [95% CI 0·90–1·29], p=0·420) was found after adjustment for intraventricular haemorrhage size and thalamic intracerebral haemorrhage. At 180 days, the treatment group had lower case fatality (46 [18%] vs saline 73 [29%], hazard ratio 0·60 [95% CI 0·41–0·86], p=0·006), but a greater proportion with mRS 5 (42 [17%] vs 21 [9%]; RR 1·99 [95% CI 1·22–3·26], p=0·007). Ventriculitis (17 [7%] alteplase vs 31 [12%] saline; RR 0·55 [95% CI 0·31–0·97], p=0·048) and serious adverse events (114 [46%] alteplase vs 151 [60%] saline; RR 0·76 [95% CI 0·64–0·90], p=0·002) were less frequent with alteplase treatment. Symptomatic bleeding (six [2%] in the alteplase group vs five [2%] in the saline group; RR 1·21 [95% CI 0·37–3·91], p=0·771) was similar. Interpretation: In patients with intraventricular haemorrhage and a routine extraventricular drain, irrigation with alteplase did not substantially improve functional outcomes at the mRS 3 cutoff compared with irrigation with saline. Protocol-based use of alteplase with extraventricular drain seems safe. Future investigation is needed to determine whether a greater frequency of complete intraventricular haemorrhage removal via alteplase produces gains in functional status

Differences in code status practice patterns among emergency clinicians working in Japan and the United States

ObjectiveThis study aimed to examine self-reported code-status practice patterns among emergency clinicians from Japan and the U.S.MethodsA cross-sectional questionnaire was distributed to emergency clinicians from one academic medical center and four general hospitals in Japan and two academic medical centers in the U.S. The questionnaire was based on a hypothetical case involving a critically ill patient with end-stage lung cancer. The questionnaire items assessed whether respondent clinicians would be likely to pose questions to patients about their preferences for medical procedures and their values and goals.ResultsA total of 176 emergency clinicians from Japan and the U.S participated. After adjusting for participants' backgrounds, emergency clinicians in Japan were less likely to pose procedure-based questions than those in the U.S. Conversely, emergency clinicians in Japan showed a statistically higher likelihood of asking 10 out of 12 value-based questions.ConclusionSignificant differences were found between emergency clinicians in Japan and the U.S. in their reported practices on posing procedure-based and patient value-based questions.Practice implicationsSerious illness communication training based in the U.S. must be adapted to the Japanese context, considering the cultural characteristics and practical responsibilities of Japanese emergency clinicians

Heterochromatic sequences in a Drosophila whole-genome shotgun assembly

BACKGROUND: Most eukaryotic genomes include a substantial repeat-rich fraction termed heterochromatin, which is concentrated in centric and telomeric regions. The repetitive nature of heterochromatic sequence makes it difficult to assemble and analyze. To better understand the heterochromatic component of the Drosophila melanogaster genome, we characterized and annotated portions of a whole-genome shotgun sequence assembly. RESULTS: WGS3, an improved whole-genome shotgun assembly, includes 20.7 Mb of draft-quality sequence not represented in the Release 3 sequence spanning the euchromatin. We annotated this sequence using the methods employed in the re-annotation of the Release 3 euchromatic sequence. This analysis predicted 297 protein-coding genes and six non-protein-coding genes, including known heterochromatic genes, and regions of similarity to known transposable elements. Bacterial artificial chromosome (BAC)-based fluorescence in situ hybridization analysis was used to correlate the genomic sequence with the cytogenetic map in order to refine the genomic definition of the centric heterochromatin; on the basis of our cytological definition, the annotated Release 3 euchromatic sequence extends into the centric heterochromatin on each chromosome arm. CONCLUSIONS: Whole-genome shotgun assembly produced a reliable draft-quality sequence of a significant part of the Drosophila heterochromatin. Annotation of this sequence defined the intron-exon structures of 30 known protein-coding genes and 267 protein-coding gene models. The cytogenetic mapping suggests that an additional 150 predicted genes are located in heterochromatin at the base of the Release 3 euchromatic sequence. Our analysis suggests strategies for improving the sequence and annotation of the heterochromatic portions of the Drosophila and other complex genomes

Scalable and Stable Ferroelectric Non-Volatile Memory at > 500 ∘^\circC

Non-volatile memory (NVM) devices that reliably operate at temperatures above 300 $^\circ$C are currently non-existent and remains a critically unmet challenge in the development of high-temperature (T) resilient electronics, necessary for many emerging, complex computing and sensing in harsh environments. Ferroelectric Al$_x$Sc$_{1-x}$N exhibits strong potential for utilization in NVM devices operating at very high temperatures (> 500 $^\circ$C) given its stable and high remnant polarization (PR) above 100 $\mu$C/cm$^2$ with demonstrated ferroelectric transition temperature (TC) > 1000 $^\circ$C. Here, we demonstrate an Al$_{0.68}$Sc$_{0.32}$N ferroelectric diode based NVM device that can reliably operate with clear ferroelectric switching up to 600 $^\circ$C with distinguishable On and Off states. The coercive field (EC) from the Pulsed I-V measurements is found to be -5.84 (EC-) and +5.98 (EC+) (+/- 0.1) MV/cm at room temperature (RT) and found to decrease with increasing temperature up to 600 $^\circ$C. The devices exhibit high remnant polarizations (> 100 $\mu$C/cm$^2$) which are stable at high temperatures. At 500 $^\circ$C, our devices show 1 million read cycles and stable On-Off ratio above 1 for > 6 hours. Finally, the operating voltages of our AlScN ferrodiodes are < 15 V at 600 $^\circ$C which is well matched and compatible with Silicon Carbide (SiC) based high temperature logic technology, thereby making our demonstration a major step towards commercialization of NVM integrated high-T computers.Comment: MS and S