Microfluidic reactors for the synthesis of nanocrystals

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2007.Vita.Includes bibliographical references.Several microfluidic reactors were designed and applied to the synthesis of colloidal semiconductor nanocrystals (NCs). Initially, a simple single-phase capillary reactor was used for the synthesis of CdSe NCs. Precursors were delivered into a section of the capillary maintained at high temperature where they decomposed and reacted to form NCs. Monodisperse, bright CdSe NC samples were prepared over a significant range of average sizes. The excellent stability and reproducibility of the continuous flow system was also demonstrated. However, a limitation of the single-phase flow approach was that slow mixing and large residence time distributions can be detrimental to the overall quality (eg. size distribution) of the NC samples produced. These limitations were overcome by designing and fabricating in silicon a gas-liquid segmented flow microreactor. In contrast to the single-phase flow, recirculation within the liquid segments provides a mechanism to exchange fluid elements located near the channel walls with those in the center. This recirculation has the dual of effect of reducing axial dispersion and greatly improving the mixing efficiency - factors which have a strong influence on the ultimate size and size distribution of NCs produced.(cont.) Compared to single-phase operation, preparation of CdSe NCs in segmented flow resulted in superior reactor throughput and narrower size distributions. Finally, the segmented flow method was extended in a microreactor designed for the synthesis of more complicated NC architectures. The design incorporated multiple inlet channels, which allowed for continuous injection of multiple precursor streams. This reactor was used to synthesize several core/shell NC structures - CdSe/ZnS, CdSe/ZnSe, and CdSe/CdxZnl-xSe.by Brian K.H. Yen.Ph.D

Integrated barcode chips for rapid, multiplexed analysis of proteins in microliter quantities of blood

As the tissue that contains the largest representation of the human proteome [1], blood is the most important fluid for clinical diagnostics [2, 3, 4]. However, although changes of plasma protein profiles reflect physiological or pathological conditions associated with many human diseases, only a handful of plasma proteins are routinely used in clinical tests. Reasons for this include the intrinsic complexity of the plasma proteome [1], the heterogeneity of human diseases and the rapid degradation of proteins in sampled blood [5]. We report an integrated microfluidic system, the integrated blood barcode chip that can sensitively sample a large panel of protein biomarkers over broad concentration ranges and within 10 min of sample collection. It enables on-chip blood separation and rapid measurement of a panel of plasma proteins from quantities of whole blood as small as those obtained by a finger prick. Our device holds potential for inexpensive, noninvasive and informative clinical diagnoses, particularly in point-of-care settings

Influence of Market Type and Time of Purchase on Bacterial Counts and Salmonella and Listeria Prevalence in Whole Chickens in Vietnam

The objective of the current study was to determine the influence of market type and sampling time on Salmonella and Listeria prevalence and bacterial counts of 180 whole chicken carcasses collected from 6 supermarkets (SM), 6 indoor markets (IM), and 6 open markets (OM) in Vietnam, at opening (T0) and 4 h after the opening (T4). Salmonella and Listeria prevalence was at least 25.6% and 42.7%, respectively. Whole birds in IM had greater Salmonella prevalence than birds from both SM and OM by 28.4% and 23.0% (P = 0.006 and 0.022, respectively). Listeria prevalence was lower in whole chickens from SM, at 56.6%, than those in IM and OM (78.6% and 73.2%, P = 0.024 and 0.089, respectively). Whole chicken carcasses had more than 10.1, 7.5, and 9.4 log colony-forming units (CFU)/g of aerobic bacteria, Escherichia coli (E. coli), and coliforms, respectively. Both E. coli and coliform counts were greater in IM than in SM (P = 0.002 and 0.006). However, only E. coli counts differed between SM (7.7 log CFU/g) and OM (8.3 log CFU/g; P = 0.024). These results highlighted high levels of bacteria and high prevalence of Salmonella and Listeria in whole chickens in retail establishments in Vietnam, posing potential food safety and public health risks

Hyperactive Neuroendocrine Secretion Causes Size, Feeding, and Metabolic Defects of C. elegans Bardet-Biedl Syndrome Mutants

Bardet-Biedl syndrome, BBS, is a rare autosomal recessive disorder with clinical presentations including polydactyly, retinopathy, hyperphagia, obesity, short stature, cognitive impairment, and developmental delays. Disruptions of BBS proteins in a variety of organisms impair cilia formation and function and the multi-organ defects of BBS have been attributed to deficiencies in various cilia-associated signaling pathways. In C. elegans, bbs genes are expressed exclusively in the sixty ciliated sensory neurons of these animals and bbs mutants exhibit sensory defects as well as body size, feeding, and metabolic abnormalities. Here we show that in contrast to many other cilia-defective mutants, C. elegans bbs mutants exhibit increased release of dense-core vesicles and organism-wide phenotypes associated with enhanced activities of insulin, neuropeptide, and biogenic amine signaling pathways. We show that the altered body size, feeding, and metabolic abnormalities of bbs mutants can be corrected to wild-type levels by abrogating the enhanced secretion of dense-core vesicles without concomitant correction of ciliary defects. These findings expand the role of BBS proteins to the regulation of dense-core-vesicle exocytosis and suggest that some features of Bardet-Biedl Syndrome may be caused by excessive neuroendocrine secretion

Features of home and neighbourhood and the liveability of older South Africans

While older people live in developing countries, little is known about the relative importance of features of their communities in influencing their liveability. We examinecomponents of home and neighbourhood among older South Africans. Linear regression analyses revealed that features of home (basic amenities, household composition, financial status and safety) and neighbourhood (ability to shop for groceries, participate in organizations and feel safe from crime) are significantly associated with life satisfaction. Approaches to liveability that are person-centred and also set within contexts beyond home and neighbourhood are needed to addressboundaries between home and neighbourhood; incorporate personal resources into liveability models and import broader environmental contexts such as health and social policy

SOD2 polymorphisms: unmasking the effect of polymorphism on splicing

BACKGROUND: The SOD2 gene encodes an antioxidant enzyme, mitochondrial superoxide dismutase. SOD2 polymorphisms are of interest because of their potential roles in the modulation of free radical-mediated macromolecular damage during aging. RESULTS: We identified a new splice variant of SOD2 in human lymphoblastoid cell lines (LCLs). The alternatively spliced product was originally detected by exon trapping of a minigene in order to examine the consequences of an intronic polymorphism found upstream of exon 4 (nucleotide 8136, 10T vs 9T). Examination of the transcripts derived from the endogenous loci in five LCLs with or without the intron 3 polymorphism revealed low levels of an in-frame deletion of exon 4 that were different from those detected by the exon trap assay. This suggested that exon trapping of the minigene unmasked the effect of the 10T vs 9T polymorphism on the splicing of the adjacent exon. We also determined the frequencies of single nucleotide polymorphisms in a sample of US African-Americans and non-African-Americans ages 65 years and older who participated in the 1999 wave of the National Long Term Care Survey (NLTCS). Particularly striking differences between African-Americans and non-African-Americans were found for the frequencies of genotypes at the 10T/9T intron 3 polymorphism. CONCLUSION: Exon trapping can unmask in vitro splicing differences caused by a 10T/9T intron 3 polymorphism. Given the recent evidence that SOD2 is in a region on chromosome 6 linked to susceptibility to hypertension, it will be of interest to investigate possible associations of this polymorphism with cardiovascular disorders

The Eighth Data Release of the Sloan Digital Sky Survey: First Data from SDSS-III

The Sloan Digital Sky Survey (SDSS) started a new phase in August 2008, with new instrumentation and new surveys focused on Galactic structure and chemical evolution, measurements of the baryon oscillation feature in the clustering of galaxies and the quasar Ly alpha forest, and a radial velocity search for planets around ~8000 stars. This paper describes the first data release of SDSS-III (and the eighth counting from the beginning of the SDSS). The release includes five-band imaging of roughly 5200 deg^2 in the Southern Galactic Cap, bringing the total footprint of the SDSS imaging to 14,555 deg^2, or over a third of the Celestial Sphere. All the imaging data have been reprocessed with an improved sky-subtraction algorithm and a final, self-consistent photometric recalibration and flat-field determination. This release also includes all data from the second phase of the Sloan Extension for Galactic Understanding and Evolution (SEGUE-2), consisting of spectroscopy of approximately 118,000 stars at both high and low Galactic latitudes. All the more than half a million stellar spectra obtained with the SDSS spectrograph have been reprocessed through an improved stellar parameters pipeline, which has better determination of metallicity for high metallicity stars.Comment: Astrophysical Journal Supplements, in press (minor updates from submitted version

A Stress Induced Source of Phonon Bursts and Quasiparticle Poisoning

The performance of superconducting qubits is degraded by a poorly characterized set of energy sources breaking the Cooper pairs responsible for superconductivity, creating a condition often called "quasiparticle poisoning." Recently, a superconductor with one of the lowest average quasiparticle densities ever measured exhibited quasiparticles primarily produced in bursts which decreased in rate with time after cooldown. Similarly, several cryogenic calorimeters used to search for dark matter have also observed an unknown source of low-energy phonon bursts that decrease in rate with time after cooldown. Here, we show that a silicon crystal glued to its holder exhibits a rate of low-energy phonon events that is more than two orders of magnitude larger than in a functionally identical crystal suspended from its holder in a low-stress state. The excess phonon event rate in the glued crystal decreases with time since cooldown, consistent with a source of phonon bursts which contributes to quasiparticle poisoning in quantum circuits and the low-energy events observed in cryogenic calorimeters. We argue that relaxation of thermally induced stress between the glue and crystal is the source of these events, and conclude that stress relaxation contributes to quasiparticle poisoning in superconducting qubits and the athermal phonon background in a broad class of rare-event searches.Comment: 13 pages, 6 figures. W. A. Page and R. K. Romani contributed equally to this work. Correspondence should be addressed to R. K. Roman

Genetic determinants of telomere length from 109,122 ancestrally diverse whole-genome sequences in TOPMed

Genetic studies on telomere length are important for understanding age-related diseases. Prior GWAS for leukocyte TL have been limited to European and Asian populations. Here, we report the first sequencing-based association study for TL across ancestrally-diverse individuals (European, African, Asian and Hispanic/Latino) from the NHLBI Trans-Omics for Precision Medicine (TOPMed) program. We used whole genome sequencing (WGS) of whole blood for variant genotype calling and the bioinformatic estimation of telomere length in n=109,122 individuals. We identified 59 sentinel variants (p-value OBFC1indicated the independent signals colocalized with cell-type specific eQTLs for OBFC1 (STN1). Using a multi-variant gene-based approach, we identified two genes newly implicated in telomere length, DCLRE1B (SNM1B) and PARN. In PheWAS, we demonstrated our TL polygenic trait scores (PTS) were associated with increased risk of cancer-related phenotypes

Polymorphisms in a Putative Enhancer at the 10q21.2 Breast Cancer Risk Locus Regulate NRBF2 Expression.

Genome-wide association studies have identified SNPs near ZNF365 at 10q21.2 that are associated with both breast cancer risk and mammographic density. To identify the most likely causal SNPs, we fine mapped the association signal by genotyping 428 SNPs across the region in 89,050 European and 12,893 Asian case and control subjects from the Breast Cancer Association Consortium. We identified four independent sets of correlated, highly trait-associated variants (iCHAVs), three of which were located within ZNF365. The most strongly risk-associated SNP, rs10995201 in iCHAV1, showed clear evidence of association with both estrogen receptor (ER)-positive (OR = 0.85 [0.82-0.88]) and ER-negative (OR = 0.87 [0.82-0.91]) disease, and was also the SNP most strongly associated with percent mammographic density. iCHAV2 (lead SNP, chr10: 64,258,684:D) and iCHAV3 (lead SNP, rs7922449) were also associated with ER-positive (OR = 0.93 [0.91-0.95] and OR = 1.06 [1.03-1.09]) and ER-negative (OR = 0.95 [0.91-0.98] and OR = 1.08 [1.04-1.13]) disease. There was weaker evidence for iCHAV4, located 5' of ADO, associated only with ER-positive breast cancer (OR = 0.93 [0.90-0.96]). We found 12, 17, 18, and 2 candidate causal SNPs for breast cancer in iCHAVs 1-4, respectively. Chromosome conformation capture analysis showed that iCHAV2 interacts with the ZNF365 and NRBF2 (more than 600 kb away) promoters in normal and cancerous breast epithelial cells. Luciferase assays did not identify SNPs that affect transactivation of ZNF365, but identified a protective haplotype in iCHAV2, associated with silencing of the NRBF2 promoter, implicating this gene in the etiology of breast cancer.This is the author accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1016/j.ajhg.2015.05.002