Microfluidic Device Architecture for Electrochemical Patterning and Detection of Multiple DNA Sequences

Electrochemical biosensors pose an attractive solution for point-of-care diagnostics because they require minimal instrumentation and they are scalable and readily integrated with microelectronics. The integration of electrochemical biosensors with microscale devices has, however, proven to be challenging due to significant incompatibilities among biomolecular stability, operation conditions of electrochemical sensors, and microfabrication techniques. Toward a solution to this problem, we have demonstrated here an electrochemical array architecture that supports the following processes in situ, within a self-enclosed microfluidic device: (a) electrode cleaning and preparation, (b) electrochemical addressing, patterning, and immobilization of sensing biomolecules at selected sensor pixels, (c) sequence-specific electrochemical detection from multiple pixels, and (d) regeneration of the sensing pixels. The architecture we have developed is general, and it should be applicable to a wide range of biosensing schemes that utilize gold–thiol self-assembled monolayer chemistry. As a proof-of-principle, we demonstrate the detection and differentiation of polymerase chain reaction (PCR) amplicons diagnostic of human (H1N1) and avian (H5N1) influenza

HPA axis reactivity to pharmacologic and psychological stressors in euthymic women with histories of postpartum versus major depression

It is unclear whether women with a history of postpartum depression (PPD) have residual, abnormal hypothalamic-pituitary-adrenal (HPA) axis reactivity, as has been reported in major depression (MDD). Further unclear is whether the abnormalities in HPA axis reactivity associated with MDD represent a stable, underlying predisposition or a state-dependent phenomenon. This study sought the following: (1) to determine if euthymic postpartum women with a history of depression have an abnormal HPA axis reactivity to pharmacologic and psychological challenges and (2) to compare HPA reactivity in women with histories of PPD versus MDD. As a secondary objective, we wanted to determine the influence of trauma history on HPA axis function. Forty-five parous (12–24 months postpartum), euthymic women with history of MDD (n = 15), PPD (n = 15), and controls (n = 15) completed pharmacologic (dexamethasone/corticotropin-releasing hormone (CRH) test [DEX/CRH]) and psychological (Trier social stress test [TSST]) challenges during the luteal phase. Outcome measures were cortisol and adrenocorticotropic hormone (ACTH) response after DEX/CRH, and blood pressure, heart rate, epinephrine, norepinephrine, and cortisol response during the TSST. All groups had robust cortisol and ACTH response to DEX/CRH and cortisol response to TSST. Groups did not differ significantly in cortisol or ACTH response to DEX/CRH or in blood pressure, heart rate, epinephrine, norepinephrine, or cortisol response to TSST. Cortisol/ACTH ratio did not differ significantly between groups. Trauma history was associated with decreased cortisol response to DEX/CRH in women with histories of MDD, which was not significant after correction (F8,125, p = 0.02, Greenhouse-Geisser corrected p = 0.11). Currently euthymic women with histories of MDD or PPD did not demonstrate residual abnormal stress responsivity following administration of either a pharmacologic or psychological stressor

Microfluidic Device Architecture for Electrochemical Patterning and Detection of Multiple DNA Sequences

Electrochemical biosensors pose an attractive solution for point-of-care diagnostics because they require minimal instrumentation and they are scalable and readily integrated with microelectronics. The integration of electrochemical biosensors with microscale devices has, however, proven to be challenging due to significant incompatibilities among biomolecular stability, operation conditions of electrochemical sensors, and microfabrication techniques. Toward a solution to this problem, we have demonstrated here an electrochemical array architecture that supports the following processes in situ, within a self-enclosed microfluidic device: (a) electrode cleaning and preparation, (b) electrochemical addressing, patterning, and immobilization of sensing biomolecules at selected sensor pixels, (c) sequence-specific electrochemical detection from multiple pixels, and (d) regeneration of the sensing pixels. The architecture we have developed is general, and it should be applicable to a wide range of biosensing schemes that utilize gold–thiol self-assembled monolayer chemistry. As a proof-of-principle, we demonstrate the detection and differentiation of polymerase chain reaction (PCR) amplicons diagnostic of human (H1N1) and avian (H5N1) influenza

The Hubble Deep Field South Flanking Fields

As part of the Hubble Deep Field South program, a set of shorter 2-orbit observations were obtained of the area adjacent to the deep fields. The WFPC2 flanking fields cover a contiguous solid angle of 48 square arcminutes. Parallel observations with the STIS and NICMOS instruments produce a patchwork of additional fields with optical and near-infrared (1.6 micron) response. Deeper parallel exposures with WFPC2 and NICMOS were obtained when STIS observed the NICMOS deep field. These deeper fields are offset from the rest, and an extended low surface brightness object is visible in the deeper WFPC2 flanking field. In this data paper, which serves as an archival record of the project, we discuss the observations and data reduction, and present SExtractor source catalogs and number counts derived from the data. Number counts are broadly consistent with previous surveys from both ground and space. Among other things, these flanking field observations are useful for defining slit masks for spectroscopic follow-up over a wider area around the deep fields, for studying large-scale structure that extends beyond the deep fields, for future supernova searches, and for number counts and morphological studies, but their ultimate utility will be defined by the astronomical community.Comment: 46 pages, 15 figures. Images and full catalogs available via the HDF-S at http://www.stsci.edu/ftp/science/hdfsouth/hdfs.html at present. The paper is accepted for the February 2003 Astronomical Journal. Full versions of the catalogs will also be available on-line from AJ after publicatio

CANDELS Observations of the Environmental Dependence of the Color-Mass-Morphology Relation at z = 1.6

We study the environmental dependence of color, stellar mass, and morphology by comparing galaxies in a forming cluster to those in the field at z = 1:6 with Hubble Space Telescope near-infrared imaging in the CANDELS/UDS field. We quantify the morphology of the galaxies using the effective radius, reff, and S\'ersic index, n. In both the cluster and field, approximately half of the bulge-dominated galaxies (n > 2) reside on the red sequence of the color-magnitude diagram, and most disk-dominated galaxies (n < 2) have colors expected for star-forming galaxies. There is weak evidence that cluster galaxies have redder rest-frame U - B colors and higher stellar masses compared to the field. Star-forming galaxies in both the cluster and field show no significant differences in their morphologies. In contrast, there is evidence that quiescent galaxies in the cluster have larger median effective radii and smaller S\'ersic indices compared to the field with a significance of 2?. These differences are most pronounced for galaxies at clustercentric distances 1 Mpc < Rproj < 1.5 Mpc, which have low S\'ersic indices and possibly larger effective radii, more consistent with star-forming galaxies at this epoch and in contrast to other quiescent galaxies. We argue that star-forming galaxies are processed under the influence of the cluster environment at distances greater than the cluster-halo virial radius. Our results are consistent with models where gas accretion onto these galaxies is suppressed from processes associated with the cluster environment.Comment: ApJ accepted, 19 pages, 10 figure

Comparative Field Evaluation of Combinations of Long-Lasting Insecticide Treated Nets and Indoor Residual Spraying, Relative to Either Method Alone, for Malaria Prevention in an Area where the main Vector is Anopheles Arabiensis.

Long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) are commonly used together in the same households to improve malaria control despite inconsistent evidence on whether such combinations actually offer better protection than nets alone or IRS alone. Comparative tests were conducted using experimental huts fitted with LLINs, untreated nets, IRS plus untreated nets, or combinations of LLINs and IRS, in an area where Anopheles arabiensis is the predominant malaria vector species. Three LLIN types, Olyset®, PermaNet 2.0® and Icon Life® nets and three IRS treatments, pirimiphos-methyl, DDT, and lambda cyhalothrin, were used singly or in combinations. We compared, number of mosquitoes entering huts, proportion and number killed, proportions prevented from blood-feeding, time when mosquitoes exited the huts, and proportions caught exiting. The tests were done for four months in dry season and another six months in wet season, each time using new intact nets. All the net types, used with or without IRS, prevented >99% of indoor mosquito bites. Adding PermaNet 2.0® and Icon Life®, but not Olyset® nets into huts with any IRS increased mortality of malaria vectors relative to IRS alone. However, of all IRS treatments, only pirimiphos-methyl significantly increased vector mortality relative to LLINs alone, though this increase was modest. Overall, median mortality of An. arabiensis caught in huts with any of the treatments did not exceed 29%. No treatment reduced entry of the vectors into huts, except for marginal reductions due to PermaNet 2.0® nets and DDT. More than 95% of all mosquitoes were caught in exit traps rather than inside huts. Where the main malaria vector is An. arabiensis, adding IRS into houses with intact pyrethroid LLINs does not enhance house-hold level protection except where the IRS employs non-pyrethroid insecticides such as pirimiphos-methyl, which can confer modest enhancements. In contrast, adding intact bednets onto IRS enhances protection by preventing mosquito blood-feeding (even if the nets are non-insecticidal) and by slightly increasing mosquito mortality (in case of LLINs). The primary mode of action of intact LLINs against An. arabiensis is clearly bite prevention rather than insecticidal activity. Therefore, where resources are limited, priority should be to ensure that everyone at risk consistently uses LLINs and that the nets are regularly replaced before being excessively torn. Measures that maximize bite prevention (e.g. proper net sizes to effectively cover sleeping spaces, stronger net fibres that resist tears and burns and net use practices that preserve net longevity), should be emphasized

Can selenium deficiency in Malawi be alleviated through consumption of agro-biofortified maize flour? Study protocol for a randomised, double-blind, controlled trial

Micronutrient deficiencies including selenium (Se) are widespread in Malawi and potentially underlie a substantial disease burden, particularly among poorer and marginalised populations. Concentrations of Se in staple cereal crops can be increased through application of Se fertilisers – a process known as agronomic biofortification (agro-biofortification) – and this may contribute to alleviating deficiencies. The Addressing Hidden Hunger with Agronomy (AHHA) trial aims to establish the efficacy of this approach for improving Se status in rural Malawi

A point-of-care clinical trial comparing insulin administered using a sliding scale versus a weight-based regimen

Background Clinical trials are widely considered the gold standard in comparative effectiveness research (CER) but the high cost and complexity of traditional trials and concerns about generalizability to broad patient populations and general clinical practice limit their appeal. Unsuccessful implementation of CER results limits the value of even the highest quality trials. Planning for a trial comparing two standard strategies of insulin administration for hospitalized patients led us to develop a new method for a clinical trial designed to be embedded directly into the clinical care setting thereby lowering the cost, increasing the pragmatic nature of the overall trial, strengthening implementation, and creating an integrated environment of research-based care

What turns galaxies off? The different morphologies of star-forming and quiescent galaxies since z~2 from CANDELS

We use HST/WFC3 imaging from the CANDELS Multicycle Treasury Survey, in conjunction with the Sloan Digital Sky Survey, to explore the evolution of galactic structure for galaxies with stellar masses >3e10M_sun from z=2.2 to the present epoch, a time span of 10Gyr. We explore the relationship between rest-frame optical color, stellar mass, star formation activity and galaxy structure. We confirm the dramatic increase from z=2.2 to the present day in the number density of non-star-forming galaxies above 3e10M_sun reported by others. We further find that the vast majority of these quiescent systems have concentrated light profiles, as parametrized by the Sersic index, and the population of concentrated galaxies grows similarly rapidly. We examine the joint distribution of star formation activity, Sersic index, stellar mass, inferred velocity dispersion, and stellar surface density. Quiescence correlates poorly with stellar mass at all z<2.2. Quiescence correlates well with Sersic index at all redshifts. Quiescence correlates well with `velocity dispersion' and stellar surface density at z>1.3, and somewhat less well at lower redshifts. Yet, there is significant scatter between quiescence and galaxy structure: while the vast majority of quiescent galaxies have prominent bulges, many of them have significant disks, and a number of bulge-dominated galaxies have significant star formation. Noting the rarity of quiescent galaxies without prominent bulges, we argue that a prominent bulge (and perhaps, by association, a supermassive black hole) is an important condition for quenching star formation on galactic scales over the last 10Gyr, in qualitative agreement with the AGN feedback paradigm.Comment: The Astrophysical Journal, in press; 20 pages with 13 figure