Effect of pooling samples on the efficiency of comparative studies using microarrays

Many biomedical experiments are carried out by pooling individual biological samples. However, pooling samples can potentially hide biological variance and give false confidence concerning the data significance. In the context of microarray experiments for detecting differentially expressed genes, recent publications have addressed the problem of the efficiency of sample-pooling, and some approximate formulas were provided for the power and sample size calculations. It is desirable to have exact formulas for these calculations and have the approximate results checked against the exact ones. We show that the difference between the approximate and exact results can be large. In this study, we have characterized quantitatively the effect of pooling samples on the efficiency of microarray experiments for the detection of differential gene expression between two classes. We present exact formulas for calculating the power of microarray experimental designs involving sample pooling and technical replications. The formulas can be used to determine the total numbers of arrays and biological subjects required in an experiment to achieve the desired power at a given significance level. The conditions under which pooled design becomes preferable to non-pooled design can then be derived given the unit cost associated with a microarray and that with a biological subject. This paper thus serves to provide guidance on sample pooling and cost effectiveness. The formulation in this paper is outlined in the context of performing microarray comparative studies, but its applicability is not limited to microarray experiments. It is also applicable to a wide range of biomedical comparative studies where sample pooling may be involved.Comment: 8 pages, 1 figure, 2 tables; to appear in Bioinformatic

H-alpha Imaging with HST+NICMOS of An Elusive Damped Ly-alpha Cloud at z=0.6

Despite previous intensive ground-based imaging and spectroscopic campaigns and wide-band HST imaging of the z=0.927 QSO 3C336 field, the galaxy that hosts the damped Ly-alpha system along this line-of-sight has eluded detection. We present a deep narrow-band H-alpha image of the field of this z=0.656 damped Ly-alpha absorber, obtained through the F108N filter of NICMOS 1 onboard the Hubble Space Telescope. The goal of this project was to detect any H-alpha emission 10 times closer than previous studies to unveil the damped absorber. We do not detect H-alpha emission between 0.05'' and 6'' (0.24 and 30 $h^{-1}$ kpc) from the QSO, with a 3-sigma flux limit of $3.70 \times 10^{-17} h^{-2}$ erg/s/cm^2 for an unresolved source, corresponding to a star formation rate (SFR) of $0.3 h^{-2}$ M_sun/yr. This leads to a 3-sigma upper limit of 0.15 M_sun/yr/kpc^2 on the SFR density, or a maximum SFR of 1.87 M_sun/yr assuming a disk of 4 kpc in diameter. This result adds to the number of low redshift damped Ly-alpha absorbers that are not associated with the central regions of Milky-Way-like disks. Damped Ly-alpha absorption can arise from high density concentrations in a variety of galactic environments including some that, despite their high local HI densities, are not conducive to widespread star formation.Comment: 18 pages, 3 figures. Replaced to match published version in ApJ, 550, 585 (Apr 1 2001

ISOLATION OF POSTSYNAPTIC DENSITIES FROM RAT BRAIN

Most synapses in the central nervous system exhibit a prominent electron-opaque specialization of the postsynaptic plasma membrane called the postsynaptic density (PSD). We have developed a procedure for the isolation of PSDs which is based on their buoyant density and their insolubility in N-lauroyl sarcosinate. Treatment of synaptic membranes with this detergent solubilizes most plasma membranes and detaches PSDs from the plasma membrane so that they can be purified on a density gradient. Isolated PSDs appear structurally intact and exhibit those properties which characterize them in tissue. The isolated PSDs are of the size, shape, and electron opacity of those seen in tissue; they stain with both ethanolic phosphotungstic acid and bismuth iodide-uranyl lead and the fraction contains cyclic 3',5'-phosphodiesterase activity. Quantitative electron microscope analysis of the PSD fraction gives an estimated purity of better than 85%. Inasmuch as the PSD is associated primarily with dendritic excitatory synapses, our PSD fraction represents the distinctive plasma membrane specialization of this specific synaptic type in isolation

Connectivity of the bay scallop (Argopecten irradians) in Buzzards Bay, Massachusetts, U.S.A.

Author Posting. © The Author(s), 2015. This is the author's version of the work. It is posted here by permission of John Wiley & Sons for personal use, not for redistribution. The definitive version was published in Fisheries Oceanography 24 (2015): 364-382, doi:10.1111/fog.12114.The harvest of bay scallops (Argopecten irradians) from Buzzards Bay, Massachusetts, USA undergoes large interannual fluctuations, varying by more than an order of magnitude in successive years. To investigate the extent to which these fluctuations may be due to yearly variations in the transport of scallop larvae from spawning areas to suitable juvenile habitat (settlement zones), a high-resolution hydrodynamic model was used to drive an individual-based model of scallop larval transport. Model results revealed that scallop spawning in Buzzards Bay occurs during a time when nearshore bay currents were principally directed up-bay in response to a persistent southwesterly sea breeze. This nearshore flow results in substantial transport of larvae from lower-bay spawning areas to settlement zones further up-bay. Averaged over the entire bay, the spawning-to-settlement zone connectivity exhibits little interannual variation. However, connectivities between individual spawning and settlement zones vary by up to an order of magnitude. The model results identified spawning areas that have the greatest probability of transporting larvae to juvenile habitat. Because managers may aim to increase scallop populations either locally or broadly, the high-connectivity spawning areas were divided into: 1) high larval retention and relatively little larval transport to adjoining settlement areas, 2) both significant larval retention and transport to more distant settlement areas, and 3) little larval retention but significant transport to distant settlement areas.This project was supported by the Woods Hole Sea Grant through award NA10OAR4170083. All modeling computations were made on the University of Massachusetts at Dartmouth’s (UMD’s) GPGPU cluster, which was acquired with support from NSF award CNS-0959382 and AFOSR DURIP award FA9550-10-1-0354.2016-07-1

A Search for Time Variation of the Fine Structure Constant

A method offering an order of magnitude sensitivity gain is described for using quasar spectra to investigate possible time or space variation in the fine structure constant, alpha. Applying the technique to a sample of 30 absorption systems, spanning redshifts 0.5 < z< 1.6, obtained with the Keck I telescope, we derive limits on variations in alpha over a wide range of epochs. For the whole sample Delta(alpha)/alpha = -1.1 +/- 0.4 x 10^{-5}. This deviation is dominated by measurements at z > 1, where Delta(alpha)/alpha = -1.9 +/- 0.5 x 10^{-5}. For z < 1, Delta(alpha)/alpha = -0.2 +/- 0.4 x 10^{-5}, consistent with other known constraints. Whilst these results are consistent with a time-varying alpha, further work is required to explore possible systematic errors in the data, although careful searches have so far not revealed any.Comment: 4 pages, 1 figure, accepted for publication in Physical Review Letter

Resoundings of the flesh: Caring for others by way of “second person” perspectivity

In bringing ourselves to the encounter with the experience of others, we bring our bodies with us—and, in doing so, we are able to resonate not only intellectually but also empathically with the other's experiences and expressions (which are given to us both verbally and nonverbally). In remaining faithful to our foundations in phenomenology (Husserl, Heidegger, Merleau-Ponty, and Levinas), we shall talk about taking notice of others from within the relational “exchange” and reflect upon what, precisely, are the experientially given “affairs” to which Husserl invited us to return. Our interest begins with the other's “first person” experience, but since we cannot access this directly, we must rely on the resonance we find within ourselves, within our own lived bodies, when we are addressed by the other, whether in word or in gesture. I am wondering what the other is experiencing and all my powers of perception are driven toward this other, whose first person experience remains just out of reach and accessible only insofar as I have this capacity for a deeper “bodily felt” awareness in which the other's experience takes possession of me. Merleau-Ponty's notion of bearing “witness” to behavior is useful in illuminating this “second person” perspective, which takes its point of departure from Husserl's (1910–1911) intersubjective reduction, by means of which we “participate in the other's positing” (1952/1989, emphasis added) and thereby grasp the meaning of the other's expression. Ultimately, the intuitive talent of the caring professional will be shown to reside in his or her being able to move beyond what the other is able to say to a more deeply felt attunement to what is being revealed to us in the other's presence. Applications to patient care are discussed

Charge Exchange and Chemical Reactions with Trapped Th3+^{3+}

We have measured the reaction rates of trapped, buffer gas cooled Th$^{3+}$ and various gases and have analyzed the reaction products using trapped ion mass spectrometry techniques. Ion trap lifetimes are usually limited by reactions with background molecules, and the high electron affinity of multiply charged ions such as Th$^{3+}$ make them more prone to loss. Our results show that reactions of Th$^{3+}$ with carbon dioxide, methane, and oxygen all occur near the classical Langevin rate, while reaction rates with argon, hydrogen, and nitrogen are orders of magnitude lower. Reactions of Th$^{3+}$ with oxygen and methane proceed primarily via charge exchange, while simultaneous charge exchange and chemical reaction occurs between Th$^{3+}$ and carbon dioxide. Loss rates of Th$^{3+}$ in helium are consistent with reaction with impurities in the gas. Reaction rates of Th$^{3+}$ with nitrogen and argon depend on the internal electronic configuration of the Th$^{3+}$.Comment: 9 pages, 10 figures, 4 tables. Submitted to PR

A systematic review of the clinical effectiveness and cost-effectiveness of pharmacological and psychological interventions for the management of obsessive-compulsive disorder in children/adolescents and adults

BACKGROUND: Obsessive-compulsive disorder (OCD) is a relatively common and disabling condition. OBJECTIVES: To determine the clinical effectiveness, acceptability and cost-effectiveness of pharmacological and psychological interventions for the treatment of OCD in children, adolescents and adults. DATA SOURCES: We searched the Cochrane Collaboration Depression, Anxiety and Neurosis Trials Registers, which includes trials from routine searches of all the major databases. Searches were conducted from inception to 31 December 2014. REVIEW METHODS: We undertook a systematic review and network meta-analysis (NMA) of the clinical effectiveness and acceptability of available treatments. Outcomes for effectiveness included mean differences in the total scores of the Yale-Brown Obsessive-Compulsive Scale or its children's version and total dropouts for acceptability. For the cost-effectiveness analysis, we developed a probabilistic model informed by the results of the NMA. All analyses were performed using OpenBUGS version 3.2.3 (members of OpenBUGS Project Management Group; see www.openbugs.net ). RESULTS: We included 86 randomised controlled trials (RCTs) in our systematic review. In the NMA we included 71 RCTs (54 in adults and 17 in children and adolescents) for effectiveness and 71 for acceptability (53 in adults and 18 in children and adolescents), comprising 7643 and 7942 randomised patients available for analysis, respectively. In general, the studies were of medium quality. The results of the NMA showed that in adults all selective serotonin reuptake inhibitors (SSRIs) and clomipramine had greater effects than drug placebo. There were no differences between SSRIs, and a trend for clomipramine to be more effective did not reach statistical significance. All active psychological therapies had greater effects than drug placebo. Behavioural therapy (BT) and cognitive therapy (CT) had greater effects than psychological placebo, but cognitive-behavioural therapy (CBT) did not. BT and CT, but not CBT, had greater effects than medications, but there are considerable uncertainty and methodological limitations that should be taken into account. In children and adolescents, CBT and BT had greater effects than drug placebo, but differences compared with psychological placebo did not reach statistical significance. SSRIs as a class showed a trend for superiority over drug placebo, but the difference did not reach statistical significance. However, the superiority of some individual drugs (fluoxetine, sertraline) was marginally statistically significant. Regarding acceptability, all interventions except clomipramine had good tolerability. In adults, CT and BT had the highest probability of being most cost-effective at conventional National Institute for Health and Care Excellence thresholds. In children and adolescents, CBT or CBT combined with a SSRI were more likely to be cost-effective. The results are uncertain and sensitive to assumptions about treatment effect and the exclusion of trials at high risk of bias. LIMITATIONS: The majority of psychological trials included patients who were taking medications. There were few studies in children and adolescents. CONCLUSIONS: In adults, psychological interventions, clomipramine, SSRIs or combinations of these are all effective, whereas in children and adolescents, psychological interventions, either as monotherapy or combined with specific SSRIs, were more likely to be effective. Future RCTs should improve their design, in particular for psychotherapy or combined interventions. STUDY REGISTRATION: The study is registered as PROSPERO CRD42012002441. FUNDING DETAILS: The National Institute for Health Research Health Technology Assessment programme

Numerical Model of a Variable-Combined-Cycle Engine for Dual Subsonic and Supersonic Cruise

Efficient high speed propulsion requires exploiting the cooling capability of the cryogenic fuel in the propulsion cycle. This paper presents the numerical model of a combined cycle engine while in air turbo-rocket configuration. Specific models of the various heat exchanger modules and the turbomachinery elements were developed to represent the physical behavior at off-design operation. The dynamic nature of the model allows the introduction of the engine control logic that limits the operation of certain subcomponents and extends the overall engine operational envelope. The specific impulse and uninstalled thrust are detailed while flying a determined trajectory between Mach 2.5 and 5 for varying throttling levels throughout the operational envelope