Neosphincter surgery for fecal incontinence: a critical and unbiased review of the relevant literature.

PubMed

Belyaev, Orlin; Müller, Christophe; Uhl, Waldemar

2006-01-01

Up until about 15 years ago the only realistic option for end-stage fecal incontinence was the creation of a permanent stoma. There have since been several developments. Dynamic graciloplasty (DGP) and artificial bowel sphincter (ABS) are well-established surgical techniques, which offer the patient a chance for continence restoration and improved quality of life; however, they are unfortunately associated with high morbidity and low success rates. Several trials have been done in an attempt to clarify the advantages and disadvantages of these methods and define their place in the second-line treatment of severe, refractory fecal incontinence. This review presents a critical and unbiased overview of the current status of neosphincter surgery according to the available data in the world literature.

Joint modelling compared with two stage methods for analysing longitudinal data and prospective outcomes: A simulation study of childhood growth and BP.

PubMed

Sayers, A; Heron, J; Smith, Adac; Macdonald-Wallis, C; Gilthorpe, M S; Steele, F; Tilling, K

2017-02-01

There is a growing debate with regards to the appropriate methods of analysis of growth trajectories and their association with prospective dependent outcomes. Using the example of childhood growth and adult BP, we conducted an extensive simulation study to explore four two-stage and two joint modelling methods, and compared their bias and coverage in estimation of the (unconditional) association between birth length and later BP, and the association between growth rate and later BP (conditional on birth length). We show that the two-stage method of using multilevel models to estimate growth parameters and relating these to outcome gives unbiased estimates of the conditional associations between growth and outcome. Using simulations, we demonstrate that the simple methods resulted in bias in the presence of measurement error, as did the two-stage multilevel method when looking at the total (unconditional) association of birth length with outcome. The two joint modelling methods gave unbiased results, but using the re-inflated residuals led to undercoverage of the confidence intervals. We conclude that either joint modelling or the simpler two-stage multilevel approach can be used to estimate conditional associations between growth and later outcomes, but that only joint modelling is unbiased with nominal coverage for unconditional associations.

Effects of the specific α4β2 nAChR antagonist, 2-fluoro-3-(4-nitrophenyl) deschloroepibatidine, on nicotine reward-related behaviors in rats and mice.

PubMed

Tobey, K M; Walentiny, D M; Wiley, J L; Carroll, F I; Damaj, M I; Azar, M R; Koob, G F; George, O; Harris, L S; Vann, R E

2012-09-01

Alleviating addiction to tobacco products could prevent millions of deaths. Investigating novel compounds selectively targeting α4β2 nAChRs hypothesized to have a key role in the rewarding effects of nicotine may be a useful approach for future treatment. The present study was designed to evaluate 2-fluoro-3-(4-nitrophenyl) deschloroepibatidine (4-nitro-PFEB), a potent competitive antagonist of neuronal α4β2 nAChRs, in several animal models related to nicotine reward: drug discrimination, intracranial self-stimulation (ICSS), conditioned place preference, and limited access to self-administration. Long Evans rats were trained in a two-lever discrimination procedure to discriminate 0.4 mg/kg nicotine (s.c.) from saline. Male Sprague-Dawley rats were stereotaxically implanted with electrodes and trained to respond for direct electrical stimulation of the medial forebrain bundle. ICR mice were evaluated using an unbiased place preference paradigm, and finally, male Wistar rats were implanted with intrajugular catheters and tested for nicotine self-administration under limited access (1 h/day). 4-Nitro-PFEB attenuated the discriminative stimulus effects of nicotine, but alone did not produce nicotine-like discriminative stimulus effects. Nicotine-induced facilitation of ICSS reward thresholds was reversed by 4-nitro-PFEB, which alone had no effect on thresholds. 4-Nitro-PFEB also blocked the conditioned place preference produced by nicotine, but alone had no effect on conditioned place preference. Finally, 4-nitro-PFEB dose-dependently decreased nicotine self-administration. These results support the hypothesis that neuronal α4β2 nAChRs play a key role in mediating the rewarding effects of nicotine and further suggest that targeting α4β2 nAChRs may yield a potential candidate for the treatment of nicotine dependence.

Implementation of a Comprehensive Curriculum in Personal Finance for Medical Fellows

PubMed Central

Bar-Or, Yuval D; Fessler, Henry E; Desai, Dipan A

2018-01-01

Introduction: Many residents and fellows complete graduate medical education having received minimal unbiased financial planning guidance. This places them at risk of making ill-informed financial decisions, which may lead to significant harm to them and their families. Therefore, we sought to provide fellows with comprehensive unbiased financial education and empower them to make timely, constructive financial decisions. Methods: A self-selected cohort of cardiovascular disease, pulmonary and critical care, and infectious disease fellows (n = 18) at a single institution attended a live, eight-hour interactive course on personal finance. The course consisted of four two-hour sessions delivered over four weeks, facilitated by an unbiased business school faculty member with expertise in personal finance. Prior to the course, all participants completed a demographic survey. After course completion, participants were offered an exit survey evaluating the course, which also asked respondents for any tangible financial decisions made as a result of the course learning.  Results: Participants included 12 women and six men, with a mean age of 33 and varying amounts of debt and financial assets. Twelve respondents completed the exit survey, and all “Strongly Agreed” that courses on financial literacy are important for trainees. In addition, 11 reported that the course helped them make important financial decisions, providing 21 examples. Conclusions: Fellows derive a significant benefit from objective financial literacy education. Graduate medical education programs should offer comprehensive financial literacy education to all graduating trainees, and that education should be provided by an unbiased expert who has no incentive to sell financial products and services. PMID:29515942

Implementation of a Comprehensive Curriculum in Personal Finance for Medical Fellows.

PubMed

Bar-Or, Yuval D; Fessler, Henry E; Desai, Dipan A; Zakaria, Sammy

2018-01-01

Many residents and fellows complete graduate medical education having received minimal unbiased financial planning guidance. This places them at risk of making ill-informed financial decisions, which may lead to significant harm to them and their families. Therefore, we sought to provide fellows with comprehensive unbiased financial education and empower them to make timely, constructive financial decisions. A self-selected cohort of cardiovascular disease, pulmonary and critical care, and infectious disease fellows (n = 18) at a single institution attended a live, eight-hour interactive course on personal finance. The course consisted of four two-hour sessions delivered over four weeks, facilitated by an unbiased business school faculty member with expertise in personal finance. Prior to the course, all participants completed a demographic survey. After course completion, participants were offered an exit survey evaluating the course, which also asked respondents for any tangible financial decisions made as a result of the course learning.  Results: Participants included 12 women and six men, with a mean age of 33 and varying amounts of debt and financial assets. Twelve respondents completed the exit survey, and all "Strongly Agreed" that courses on financial literacy are important for trainees. In addition, 11 reported that the course helped them make important financial decisions, providing 21 examples. Fellows derive a significant benefit from objective financial literacy education. Graduate medical education programs should offer comprehensive financial literacy education to all graduating trainees, and that education should be provided by an unbiased expert who has no incentive to sell financial products and services.

Unbiased split variable selection for random survival forests using maximally selected rank statistics.

PubMed

Wright, Marvin N; Dankowski, Theresa; Ziegler, Andreas

2017-04-15

The most popular approach for analyzing survival data is the Cox regression model. The Cox model may, however, be misspecified, and its proportionality assumption may not always be fulfilled. An alternative approach for survival prediction is random forests for survival outcomes. The standard split criterion for random survival forests is the log-rank test statistic, which favors splitting variables with many possible split points. Conditional inference forests avoid this split variable selection bias. However, linear rank statistics are utilized by default in conditional inference forests to select the optimal splitting variable, which cannot detect non-linear effects in the independent variables. An alternative is to use maximally selected rank statistics for the split point selection. As in conditional inference forests, splitting variables are compared on the p-value scale. However, instead of the conditional Monte-Carlo approach used in conditional inference forests, p-value approximations are employed. We describe several p-value approximations and the implementation of the proposed random forest approach. A simulation study demonstrates that unbiased split variable selection is possible. However, there is a trade-off between unbiased split variable selection and runtime. In benchmark studies of prediction performance on simulated and real datasets, the new method performs better than random survival forests if informative dichotomous variables are combined with uninformative variables with more categories and better than conditional inference forests if non-linear covariate effects are included. In a runtime comparison, the method proves to be computationally faster than both alternatives, if a simple p-value approximation is used. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Using water quality to assess ecological condition in the St. Marys River and Huron-Erie Corridor

EPA Science Inventory

The St. Marys River and Huron-Erie-Corridor were assessed by EPA for the first time in 2014-2016 as part of the National Coastal Condition Assessment (NCCA). NCCA uses a probabilistic survey design to allow unbiased assessment of ecological condition across the entire Great Lakes...

Unbiased multi-fidelity estimate of failure probability of a free plane jet

NASA Astrophysics Data System (ADS)

Marques, Alexandre; Kramer, Boris; Willcox, Karen; Peherstorfer, Benjamin

2017-11-01

Estimating failure probability related to fluid flows is a challenge because it requires a large number of evaluations of expensive models. We address this challenge by leveraging multiple low fidelity models of the flow dynamics to create an optimal unbiased estimator. In particular, we investigate the effects of uncertain inlet conditions in the width of a free plane jet. We classify a condition as failure when the corresponding jet width is below a small threshold, such that failure is a rare event (failure probability is smaller than 0.001). We estimate failure probability by combining the frameworks of multi-fidelity importance sampling and optimal fusion of estimators. Multi-fidelity importance sampling uses a low fidelity model to explore the parameter space and create a biasing distribution. An unbiased estimate is then computed with a relatively small number of evaluations of the high fidelity model. In the presence of multiple low fidelity models, this framework offers multiple competing estimators. Optimal fusion combines all competing estimators into a single estimator with minimal variance. We show that this combined framework can significantly reduce the cost of estimating failure probabilities, and thus can have a large impact in fluid flow applications. This work was funded by DARPA.

AD620SQ/883B Total Ionizing Dose Radiation Lot Acceptance Report for RESTORE-LEO

NASA Technical Reports Server (NTRS)

Burton, Noah; Campola, Michael

2017-01-01

A Radiation Lot Acceptance Test was performed on the AD620SQ/883B, Lot 1708D, in accordance with MIL-STD-883, Method 1019, Condition D. Using a Co-60 source 4 biased parts and 4 unbiased parts were irradiated at 10 mrad/s (0.036 krad/hr) in intervals of approximately 1 krad from 3-10 krads, and ones of 5 krads from 10-25 krads, where it was annealed while unbiased at 25 degrees Celsius, for 2 days, and then, subsequently, annealed while biased at 25 degrees celsius, for another 7 days.

Obseving Nurse Interaction With Infusion Pump Technologies

DTIC Science & Technology

2005-01-01

24 Observations of the medication administration process , as described below, were performed to provide data to the FMEA team on nursing practice...involves an FMEA of the medication administration process using the observation data as input into the assessment process .29 One use of the...invaluable to the FMEA team in many ways. First, it allowed for an unbiased and nonjudgmental look at the actual nursing processes in place, as

The effects of exogenous CCK-8 on the acquisition and expression of morphine-induced CPP.

PubMed

Wen, Di; Cong, Bin; Ma, Chunling; Yang, Shengchang; Yu, Hailei; Ni, Zhiyu; Li, Shujin

2012-02-21

Cholecystokinin octapeptide (CCK-8) is the most potent endogenous anti-opioid peptide and regulates a variety of physiological processes. In our previous study, we found that exogenous CCK-8 attenuated naloxone-induced withdrawal symptoms, but the possible regulative effects of CCK-8 on the rewarding effects of morphine were not examined. In the present study, we aimed to determine the exact effects of exogenous CCK-8 at various doses on the rewarding action of morphine by utilizing the unbiased conditioned place preference (CPP) paradigm. We therefore examined the effects of CCK-8 on the acquisition, expression and extinction of morphine-induced CPP and on locomotor activity. The results showed that CCK-8 (0.01-1μg, i.c.v.), administered alone, induced neither CPP nor place aversion, but blocked the acquisition of CPP when administered with 10mg/kg morphine. The highest dose of CCK-8 (1μg) administered before CPP testing increased CPP and, along with lower doses (0.1μg), reduced its extinction. In addition, the highest dose (1μg) of CCK-8 suppressed locomotor activity. Our study provides the first behavioral evidence for the inhibitory effects of exogenous CCK-8 on rewarding activity and reveals significant effects of exogenous CCK-8 on various stages of place preference and the development of opioid dependence. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

On the Bias-Amplifying Effect of Near Instruments in Observational Studies

ERIC Educational Resources Information Center

Steiner, Peter M.; Kim, Yongnam

2014-01-01

In contrast to randomized experiments, the estimation of unbiased treatment effects from observational data requires an analysis that conditions on all confounding covariates. Conditioning on covariates can be done via standard parametric regression techniques or nonparametric matching like propensity score (PS) matching. The regression or…

Effects of Acute Withdrawal on Ethanol-Induced Conditioned Place Preference in DBA/2J mice

PubMed Central

Dreumont, Sarah E.; Cunningham, Christopher L.

2013-01-01

Rationale Re-exposure to ethanol during acute withdrawal might facilitate the transition to alcoholism by enhancing the rewarding effect of ethanol. Objective The conditioned place preference (CPP) procedure was used to test whether ethanol reward is enhanced during acute withdrawal. Methods DBA/2J mice were exposed to an unbiased one-compartment CPP procedure. Ethanol (0.75, 1.0 or 1.5 g/kg IP) was paired with a distinctive floor cue (CS+), whereas saline was paired with a different floor cue (CS−). The Withdrawal (W) group received CS+ trials during acute withdrawal produced by a large dose of ethanol (4 g/kg) given 8 h before each trial. The No Withdrawal (NW) group did not experience acute withdrawal during conditioning trials, but was matched for acute withdrawal experience. Floor preference was tested in the absence of ethanol or acute withdrawal. Results All groups eventually showed a dose-dependent preference for the ethanol-paired cue, but development of CPP was generally more rapid and stable in the W groups than in the NW groups. Acute withdrawal suppressed the normal activating effect of ethanol during CS+ trials, but there were no group differences in test activity. Conclusions Acute withdrawal enhanced ethanol’s rewarding effect as indexed by CPP. Since this effect depended on ethanol exposure during acute withdrawal, the enhancement of ethanol reward was likely mediated by the alleviation of acute withdrawal, i.e., negative reinforcement. Enhancement of ethanol reward during acute withdrawal may be a key component in the shift from episodic to chronic ethanol consumption that characterizes alcoholism. PMID:24096534

Estimation After a Group Sequential Trial.

PubMed

Milanzi, Elasma; Molenberghs, Geert; Alonso, Ariel; Kenward, Michael G; Tsiatis, Anastasios A; Davidian, Marie; Verbeke, Geert

2015-10-01

Group sequential trials are one important instance of studies for which the sample size is not fixed a priori but rather takes one of a finite set of pre-specified values, dependent on the observed data. Much work has been devoted to the inferential consequences of this design feature. Molenberghs et al (2012) and Milanzi et al (2012) reviewed and extended the existing literature, focusing on a collection of seemingly disparate, but related, settings, namely completely random sample sizes, group sequential studies with deterministic and random stopping rules, incomplete data, and random cluster sizes. They showed that the ordinary sample average is a viable option for estimation following a group sequential trial, for a wide class of stopping rules and for random outcomes with a distribution in the exponential family. Their results are somewhat surprising in the sense that the sample average is not optimal, and further, there does not exist an optimal, or even, unbiased linear estimator. However, the sample average is asymptotically unbiased, both conditionally upon the observed sample size as well as marginalized over it. By exploiting ignorability they showed that the sample average is the conventional maximum likelihood estimator. They also showed that a conditional maximum likelihood estimator is finite sample unbiased, but is less efficient than the sample average and has the larger mean squared error. Asymptotically, the sample average and the conditional maximum likelihood estimator are equivalent. This previous work is restricted, however, to the situation in which the the random sample size can take only two values, N = n or N = 2 n . In this paper, we consider the more practically useful setting of sample sizes in a the finite set { n 1 , n 2 , …, n L }. It is shown that the sample average is then a justifiable estimator , in the sense that it follows from joint likelihood estimation, and it is consistent and asymptotically unbiased. We also show why simulations can give the false impression of bias in the sample average when considered conditional upon the sample size. The consequence is that no corrections need to be made to estimators following sequential trials. When small-sample bias is of concern, the conditional likelihood estimator provides a relatively straightforward modification to the sample average. Finally, it is shown that classical likelihood-based standard errors and confidence intervals can be applied, obviating the need for technical corrections.

Autocorrelation analysis for the unbiased determination of power-law exponents in single-quantum-dot blinking.

PubMed

Houel, Julien; Doan, Quang T; Cajgfinger, Thomas; Ledoux, Gilles; Amans, David; Aubret, Antoine; Dominjon, Agnès; Ferriol, Sylvain; Barbier, Rémi; Nasilowski, Michel; Lhuillier, Emmanuel; Dubertret, Benoît; Dujardin, Christophe; Kulzer, Florian

2015-01-27

We present an unbiased and robust analysis method for power-law blinking statistics in the photoluminescence of single nanoemitters, allowing us to extract both the bright- and dark-state power-law exponents from the emitters' intensity autocorrelation functions. As opposed to the widely used threshold method, our technique therefore does not require discriminating the emission levels of bright and dark states in the experimental intensity timetraces. We rely on the simultaneous recording of 450 emission timetraces of single CdSe/CdS core/shell quantum dots at a frame rate of 250 Hz with single photon sensitivity. Under these conditions, our approach can determine ON and OFF power-law exponents with a precision of 3% from a comparison to numerical simulations, even for shot-noise-dominated emission signals with an average intensity below 1 photon per frame and per quantum dot. These capabilities pave the way for the unbiased, threshold-free determination of blinking power-law exponents at the microsecond time scale.

Behavioral and Molecular Analysis of Nicotine-Conditioned Place Preference in Zebrafish

PubMed Central

Kedikian, Ximena; Faillace, Maria Paula; Bernabeu, Ramón

2013-01-01

Studies using mice and rats have demonstrated that nicotine induces a conditioned place preference (CPP), with more effective results obtained by using biased procedures. Zebrafish have also been used as a model system to identify factors influencing nicotine-associated reward by using an unbiased design. Here, we report that zebrafish exhibited putative nicotine biased CPP to an initially aversive compartment (nicotine-paired group). A counterbalanced nicotine-exposed control group did not show a significant preference shift, providing evidence that the preference shift in the nicotine-paired group was not due to a reduction of aversion for this compartment. Zebrafish preference was corroborated by behavioral analysis of several indicators of drug preference, such as time spent in the drug-paired side, number of entries to the drug-paired side, and distance traveled. These results provided strong evidence that zebrafish may actually develop a preference for nicotine, although the drug was administrated in an aversive place for the fish, which was further supported by molecular studies. Reverse transcription-quantitative real-time PCR analysis depicted a significant increase in the expression of α7 and α6 but not α4 and β2 subunits of the nicotinic receptor in nicotine-paired zebrafish brains. In contrast, zebrafish brains from the counterbalanced nicotine group showed no significant changes. Moreover, CREB phosphorylation, an indicator of neural activity, accompanied the acquisition of nicotine-CPP. Our studies offered an incremental value to the drug addiction field, because they further describe behavioral features of CPP to nicotine in zebrafish. The results suggested that zebrafish exposed to nicotine in an unfriendly environment can develop a preference for that initially aversive place, which is likely due to the rewarding effect of nicotine. Therefore, this model can be used to screen exogenous and endogenous molecules involved in nicotine-associated reward in vertebrates. PMID:23894483

Mutually unbiased product bases for multiple qudits

DOE Office of Scientific and Technical Information (OSTI.GOV)

McNulty, Daniel; Pammer, Bogdan; Weigert, Stefan

We investigate the interplay between mutual unbiasedness and product bases for multiple qudits of possibly different dimensions. A product state of such a system is shown to be mutually unbiased to a product basis only if each of its factors is mutually unbiased to all the states which occur in the corresponding factors of the product basis. This result implies both a tight limit on the number of mutually unbiased product bases which the system can support and a complete classification of mutually unbiased product bases for multiple qubits or qutrits. In addition, only maximally entangled states can be mutuallymore » unbiased to a maximal set of mutually unbiased product bases.« less

Influence of cholinesterase inhibitors, donepezil and rivastigmine on the acquisition, expression, and reinstatement of morphine-induced conditioned place preference in rats.

PubMed

Gawel, Kinga; Labuz, Krzysztof; Jenda, Malgorzata; Silberring, Jerzy; Kotlinska, Jolanta H

2014-07-15

The influence of systemic administration of cholinesterase inhibitors, donepezil and rivastigmine on the acquisition, expression, and reinstatement of morphine-induced conditioned place preference (CPP) was examined in rats. Additionally, this study aimed to compare the effects of donepezil, which selectively inhibits acetylcholinesterase, and rivastigmine, which inhibits both acetylcholinesterase and butyrylcholinesterase on morphine reward. Morphine-induced CPP (unbiased method) was induced by four injections of morphine (5 mg/kg, i.p.). Donepezil (0.5, 1, and 3 mg/kg, i.p.) or rivastigmine (0.03, 0.5, and 1 mg/kg, i.p.) were given 20 min before morphine during conditioning phase and 20 min before the expression or reinstatement of morphine-induced CPP. Our results indicated that both inhibitors of cholinesterase attenuated the acquisition and expression of morphine CPP. The results were more significant after rivastigmine due to a broader inhibitory spectrum of this drug. Moreover, donepezil (1 mg/kg) and rivastigmine (0.5 mg/kg) attenuated the morphine CPP reinstated by priming injection of 5mg/kg morphine. These properties of both cholinesterase inhibitors were reversed by mecamylamine (3 mg/kg, i.p.), a nicotinic acetylcholine receptor antagonist but not scopolamine (0.5 mg/kg, i.p.), a muscarinic acetylcholine receptor antagonist. All effects of cholinesterase inhibitors were observed at the doses that had no effects on locomotor activity of animals. Our results suggest beneficial role of cholinesterase inhibitors in reduction of morphine reward and morphine-induced seeking behavior. Finally, we found that the efficacy of cholinesterase inhibitors in attenuating reinstatement of morphine CPP provoked by priming injection may be due to stimulation of nicotinic acetylcholine receptors. Copyright © 2014 Elsevier B.V. All rights reserved.

Constructing a Time-Invariant Measure of the Socio-economic Status of U.S. Census Tracts.

PubMed

Miles, Jeremy N; Weden, Margaret M; Lavery, Diana; Escarce, José J; Cagney, Kathleen A; Shih, Regina A

2016-02-01

Contextual research on time and place requires a consistent measurement instrument for neighborhood conditions in order to make unbiased inferences about neighborhood change. We develop such a time-invariant measure of neighborhood socio-economic status (NSES) using exploratory and confirmatory factor analyses fit to census data at the tract level from the 1990 and 2000 U.S. Censuses and the 2008-2012 American Community Survey. A single factor model fit the data well at all three time periods, and factor loadings--but not indicator intercepts--could be constrained to equality over time without decrement to fit. After addressing remaining longitudinal measurement bias, we found that NSES increased from 1990 to 2000, and then--consistent with the timing of the "Great Recession"--declined in 2008-2012 to a level approaching that of 1990. Our approach for evaluating and adjusting for time-invariance is not only instructive for studies of NSES but also more generally for longitudinal studies in which the variable of interest is a latent construct.

Mutually unbiased projectors and duality between lines and bases in finite quantum systems

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shalaby, M.; Vourdas, A., E-mail: a.vourdas@bradford.ac.uk

2013-10-15

Quantum systems with variables in the ring Z(d) are considered, and the concepts of weak mutually unbiased bases and mutually unbiased projectors are discussed. The lines through the origin in the Z(d)×Z(d) phase space, are classified into maximal lines (sets of d points), and sublines (sets of d{sub i} points where d{sub i}|d). The sublines are intersections of maximal lines. It is shown that there exists a duality between the properties of lines (resp., sublines), and the properties of weak mutually unbiased bases (resp., mutually unbiased projectors). -- Highlights: •Lines in discrete phase space. •Bases in finite quantum systems. •Dualitymore » between bases and lines. •Weak mutually unbiased bases.« less

A Bayesian Approach to Identifying Structural Nonlinearity using Free-Decay Response: Application to Damage Detection in Composites

DTIC Science & Technology

2010-03-03

obtainable while for the free-decay problem we simply have to include the initial conditions as random variables to be predicted. A different approach that...important and useful properties of MLEs is that, under regularity conditions , they are asymptotically unbiased and possess the minimum possible...becomes pLðzjh;s2G;MiÞ (i.e. the likelihood is conditional on the specified model). However, in this work we will only consider a single model and drop the

Detection of sea otters in boat-based surveys of Prince William Sound, Alaska

USGS Publications Warehouse

Udevitz, Mark S.; Bodkin, James L.; Costa, Daniel P.

1995-01-01

Boat-based surveys have been commonly used to monitor sea otter populations, but there has been little quantitative work to evaluate detection biases that may affect these surveys. We used ground-based observers to investigate sea otter detection probabilities in a boat-based survey of Prince William Sound, Alaska. We estimated that 30% of the otters present on surveyed transects were not detected by boat crews. Approximately half (53%) of the undetected otters were missed because the otters left the transects, apparently in response to the approaching boat. Unbiased estimates of detection probabilities will be required for obtaining unbiased population estimates from boat-based surveys of sea otters. Therefore, boat-based surveys should include methods to estimate sea otter detection probabilities under the conditions specific to each survey. Unbiased estimation of detection probabilities with ground-based observers requires either that the ground crews detect all of the otters in observed subunits, or that there are no errors in determining which crews saw each detected otter. Ground-based observer methods may be appropriate in areas where nearly all of the sea otter habitat is potentially visible from ground-based vantage points.

Power Generation from a Radiative Thermal Source Using a Large-Area Infrared Rectenna

NASA Astrophysics Data System (ADS)

Shank, Joshua; Kadlec, Emil A.; Jarecki, Robert L.; Starbuck, Andrew; Howell, Stephen; Peters, David W.; Davids, Paul S.

2018-05-01

Electrical power generation from a moderate-temperature thermal source by means of direct conversion of infrared radiation is important and highly desirable for energy harvesting from waste heat and micropower applications. Here, we demonstrate direct rectified power generation from an unbiased large-area nanoantenna-coupled tunnel diode rectifier called a rectenna. Using a vacuum radiometric measurement technique with irradiation from a temperature-stabilized thermal source, a generated power density of 8 nW /cm2 is observed at a source temperature of 450 °C for the unbiased rectenna across an optimized load resistance. The optimized load resistance for the peak power generation for each temperature coincides with the tunnel diode resistance at zero bias and corresponds to the impedance matching condition for a rectifying antenna. Current-voltage measurements of a thermally illuminated large-area rectenna show current zero crossing shifts into the second quadrant indicating rectification. Photon-assisted tunneling in the unbiased rectenna is modeled as the mechanism for the large short-circuit photocurrents observed where the photon energy serves as an effective bias across the tunnel junction. The measured current and voltage across the load resistor as a function of the thermal source temperature represents direct current electrical power generation.

Automated systematic random sampling and Cavalieri stereology of histologic sections demonstrating acute tubular necrosis after cardiac arrest and cardiopulmonary resuscitation in the mouse.

PubMed

Wakasaki, Rumie; Eiwaz, Mahaba; McClellan, Nicholas; Matsushita, Katsuyuki; Golgotiu, Kirsti; Hutchens, Michael P

2018-06-14

A technical challenge in translational models of kidney injury is determination of the extent of cell death. Histologic sections are commonly analyzed by area morphometry or unbiased stereology, but stereology requires specialized equipment. Therefore, a challenge to rigorous quantification would be addressed by an unbiased stereology tool with reduced equipment dependence. We hypothesized that it would be feasible to build a novel software component which would facilitate unbiased stereologic quantification on scanned slides, and that unbiased stereology would demonstrate greater precision and decreased bias compared with 2D morphometry. We developed a macro for the widely used image analysis program, Image J, and performed cardiac arrest with cardiopulmonary resuscitation (CA/CPR, a model of acute cardiorenal syndrome) in mice. Fluorojade-B stained kidney sections were analyzed using three methods to quantify cell death: gold standard stereology using a controlled stage and commercially-available software, unbiased stereology using the novel ImageJ macro, and quantitative 2D morphometry also using the novel macro. There was strong agreement between both methods of unbiased stereology (bias -0.004±0.006 with 95% limits of agreement -0.015 to 0.007). 2D morphometry demonstrated poor agreement and significant bias compared to either method of unbiased stereology. Unbiased stereology is facilitated by a novel macro for ImageJ and results agree with those obtained using gold-standard methods. Automated 2D morphometry overestimated tubular epithelial cell death and correlated modestly with values obtained from unbiased stereology. These results support widespread use of unbiased stereology for analysis of histologic outcomes of injury models.

APPLICATION OF A MULTIPURPOSE UNEQUAL-PROBABILITY STREAM SURVEY IN THE MID-ATLANTIC COASTAL PLAIN

EPA Science Inventory

A stratified random sample with unequal-probability selection was used to design a multipurpose survey of headwater streams in the Mid-Atlantic Coastal Plain. Objectives for data from the survey include unbiased estimates of regional stream conditions, and adequate coverage of un...

Entropic uncertainty relations and locking: Tight bounds for mutually unbiased bases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ballester, Manuel A.; Wehner, Stephanie

We prove tight entropic uncertainty relations for a large number of mutually unbiased measurements. In particular, we show that a bound derived from the result by Maassen and Uffink [Phys. Rev. Lett. 60, 1103 (1988)] for two such measurements can in fact be tight for up to {radical}(d) measurements in mutually unbiased bases. We then show that using more mutually unbiased bases does not always lead to a better locking effect. We prove that the optimal bound for the accessible information using up to {radical}(d) specific mutually unbiased bases is log d/2, which is the same as can be achievedmore » by using only two bases. Our result indicates that merely using mutually unbiased bases is not sufficient to achieve a strong locking effect and we need to look for additional properties.« less

The effect of memory and context changes on color matches to real objects.

PubMed

Allred, Sarah R; Olkkonen, Maria

2015-07-01

Real-world color identification tasks often require matching the color of objects between contexts and after a temporal delay, thus placing demands on both perceptual and memory processes. Although the mechanisms of matching colors between different contexts have been widely studied under the rubric of color constancy, little research has investigated the role of long-term memory in such tasks or how memory interacts with color constancy. To investigate this relationship, observers made color matches to real study objects that spanned color space, and we independently manipulated the illumination impinging on the objects, the surfaces in which objects were embedded, and the delay between seeing the study object and selecting its color match. Adding a 10-min delay increased both the bias and variability of color matches compared to a baseline condition. These memory errors were well accounted for by modeling memory as a noisy but unbiased version of perception constrained by the matching methods. Surprisingly, we did not observe significant increases in errors when illumination and surround changes were added to the 10-minute delay, although the context changes alone did elicit significant errors.

NMDA receptor blockade in the prelimbic cortex activates the mesolimbic system and dopamine-dependent opiate reward signaling.

PubMed

Tan, Huibing; Rosen, Laura G; Ng, Garye A; Rushlow, Walter J; Laviolette, Steven R

2014-12-01

N-Methyl-D-aspartate (NMDA) receptors in the medial prefrontal cortex (mPFC) are involved in opiate reward processing and modulate sub-cortical dopamine (DA) activity. NMDA receptor blockade in the prelimbic (PLC) division of the mPFC strongly potentiates the rewarding behavioural properties of normally sub-reward threshold doses of opiates. However, the possible functional interactions between cortical NMDA and sub-cortical DAergic motivational neural pathways underlying these effects are not understood. This study examines how NMDA receptor modulation in the PLC influences opiate reward processing via interactions with sub-cortical DAergic transmission. We further examined whether direct intra-PLC NMDA receptor modulation may activate DA-dependent opiate reward signaling via interactions with the ventral tegmental area (VTA). Using an unbiased place conditioning procedure (CPP) in rats, we performed bilateral intra-PLC microinfusions of the competitive NMDA receptor antagonist, (2R)-amino-5-phosphonovaleric acid (AP-5), prior to behavioural morphine place conditioning and challenged the rewarding effects of morphine with DA receptor blockade. We next examined the effects of intra-PLC NMDA receptor blockade on the spontaneous activity patterns of presumptive VTA DA or GABAergic neurons, using single-unit, extracellular in vivo neuronal recordings. We show that intra-PLC NMDA receptor blockade strongly activates sub-cortical DA neurons within the VTA while inhibiting presumptive non-DA GABAergic neurons. Behaviourally, NMDA receptor blockade activates a DA-dependent opiate reward system, as pharmacological blockade of DA transmission blocked morphine reward only in the presence of intra-PLC NMDA receptor antagonism. These findings demonstrate a cortical NMDA-mediated mechanism controlling mesolimbic DAergic modulation of opiate reward processing.

Regression sampling: some results for resource managers and researchers

Treesearch

William G. O' Regan; Robert W. Boyd

1974-01-01

Regression sampling is widely used in natural resources management and research to estimate quantities of resources per unit area. This note brings together results found in the statistical literature in the application of this sampling technique. Conditional and unconditional estimators are listed and for each estimator, exact variances and unbiased estimators for the...

Characterization of Radiation Hardened Bipolar Linear Devices for High Total Dose Missions

NASA Technical Reports Server (NTRS)

McClure, Steven S.; Harris, Richard D.; Rax, Bernard G.; Thorbourn, Dennis O.

2012-01-01

Radiation hardened linear devices are characterized for performance in combined total dose and displacement damage environments for a mission scenario with a high radiation level. Performance at low and high dose rate for both biased and unbiased conditions is compared and the impact to hardness assurance methodology is discussed.

Meaner king uses biased bases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Reimpell, Michael; Werner, Reinhard F.

2007-06-15

The mean king problem is a quantum mechanical retrodiction problem, in which Alice has to name the outcome of an ideal measurement made in one of several different orthonormal bases. Alice is allowed to prepare the state of the system and to do a final measurement, possibly including an entangled copy. However, Alice gains knowledge about which basis was measured only after she no longer has access to the quantum system or its copy. We give a necessary and sufficient condition on the bases, for Alice to have a strategy to solve this problem, without assuming that the bases aremore » mutually unbiased. The condition requires the existence of an overall joint probability distribution for random variables, whose marginal pair distributions are fixed as the transition probability matrices of the given bases. In particular, in the qubit case the problem is decided by Bell's original three variable inequality. In the standard setting of mutually unbiased bases, when they do exist, Alice can always succeed. However, for randomly chosen bases her success probability rapidly goes to zero with increasing dimension.« less

Meaner king uses biased bases

NASA Astrophysics Data System (ADS)

Reimpell, Michael; Werner, Reinhard F.

2007-06-01

The mean king problem is a quantum mechanical retrodiction problem, in which Alice has to name the outcome of an ideal measurement made in one of several different orthonormal bases. Alice is allowed to prepare the state of the system and to do a final measurement, possibly including an entangled copy. However, Alice gains knowledge about which basis was measured only after she no longer has access to the quantum system or its copy. We give a necessary and sufficient condition on the bases, for Alice to have a strategy to solve this problem, without assuming that the bases are mutually unbiased. The condition requires the existence of an overall joint probability distribution for random variables, whose marginal pair distributions are fixed as the transition probability matrices of the given bases. In particular, in the qubit case the problem is decided by Bell’s original three variable inequality. In the standard setting of mutually unbiased bases, when they do exist, Alice can always succeed. However, for randomly chosen bases her success probability rapidly goes to zero with increasing dimension.

The novel non-imidazole histamine H3 receptor antagonist DL77 reduces voluntary alcohol intake and ethanol-induced conditioned place preference in mice.

PubMed

Bahi, Amine; Sadek, Bassem; Nurulain, Syed M; Łażewska, Dorota; Kieć-Kononowicz, Katarzyna

2015-11-01

It has become clear that histamine H3 receptors (H3R) have been implicated in modulating ethanol intake and preference in laboratory animals. The novel non-imidazole H3R antagonist DL77 with excellent selectivity profile shows high in-vivo potency as well as in-vitro antagonist affinity with ED50 of 2.1 ± 0.2 mg/kg and pKi=8.08, respectively. In the present study, and applying an unlimited access two-bottle choice procedure, the anti-alcohol effects of the H3R antagonist, DL77 (0, 3, 10 and 30 mg/kg; i.p.), were investigated in adult mice. In this C57BL/6 line, effects of DL77 on voluntary alcohol intake and preference, as well as on total fluid intake were evaluated. Results have shown that DL77, dose-dependently, reduced both ethanol intake and preference. These effects were very selective as both saccharin and quinine, used to control for taste sensitivity, and intakes were not affected following DL77 pre-application. More importantly, systemic administration of DL77 (10 mg/kg) during acquisition inhibited ethanol-induced conditioned-place preference (EtOH-CPP) as measured using an unbiased protocol. The anti-alcohol activity observed for DL77 was abrogated when mice were pretreated with the selective H3R agonist R-(α)-methyl-histamine (RAMH) (10 mg/kg), or with the CNS penetrant H1R antagonist pyrilamine (PYR) (10mg/kg). These results suggest that DL77 has a predominant role in two in vivo effects of ethanol. Therefore, signaling via H3R is essential for ethanol-related consumption and conditioned reward and may represent a novel therapeutic pharmacological target to tackle ethanol abuse and alcoholism. Copyright © 2015 Elsevier Inc. All rights reserved.

Maximum likelihood: Extracting unbiased information from complex networks

NASA Astrophysics Data System (ADS)

Garlaschelli, Diego; Loffredo, Maria I.

2008-07-01

The choice of free parameters in network models is subjective, since it depends on what topological properties are being monitored. However, we show that the maximum likelihood (ML) principle indicates a unique, statistically rigorous parameter choice, associated with a well-defined topological feature. We then find that, if the ML condition is incompatible with the built-in parameter choice, network models turn out to be intrinsically ill defined or biased. To overcome this problem, we construct a class of safely unbiased models. We also propose an extension of these results that leads to the fascinating possibility to extract, only from topological data, the “hidden variables” underlying network organization, making them “no longer hidden.” We test our method on World Trade Web data, where we recover the empirical gross domestic product using only topological information.

Statistical Properties of Maximum Likelihood Estimators of Power Law Spectra Information

NASA Technical Reports Server (NTRS)

Howell, L. W., Jr.

2003-01-01

A simple power law model consisting of a single spectral index, sigma(sub 2), is believed to be an adequate description of the galactic cosmic-ray (GCR) proton flux at energies below 10(exp 13) eV, with a transition at the knee energy, E(sub k), to a steeper spectral index sigma(sub 2) greater than sigma(sub 1) above E(sub k). The maximum likelihood (ML) procedure was developed for estimating the single parameter sigma(sub 1) of a simple power law energy spectrum and generalized to estimate the three spectral parameters of the broken power law energy spectrum from simulated detector responses and real cosmic-ray data. The statistical properties of the ML estimator were investigated and shown to have the three desirable properties: (Pl) consistency (asymptotically unbiased), (P2) efficiency (asymptotically attains the Cramer-Rao minimum variance bound), and (P3) asymptotically normally distributed, under a wide range of potential detector response functions. Attainment of these properties necessarily implies that the ML estimation procedure provides the best unbiased estimator possible. While simulation studies can easily determine if a given estimation procedure provides an unbiased estimate of the spectra information, and whether or not the estimator is approximately normally distributed, attainment of the Cramer-Rao bound (CRB) can only be ascertained by calculating the CRB for an assumed energy spectrum- detector response function combination, which can be quite formidable in practice. However, the effort in calculating the CRB is very worthwhile because it provides the necessary means to compare the efficiency of competing estimation techniques and, furthermore, provides a stopping rule in the search for the best unbiased estimator. Consequently, the CRB for both the simple and broken power law energy spectra are derived herein and the conditions under which they are stained in practice are investigated.

Towards a sampling strategy for the assessment of forest condition at European level: combining country estimates.

PubMed

Travaglini, Davide; Fattorini, Lorenzo; Barbati, Anna; Bottalico, Francesca; Corona, Piermaria; Ferretti, Marco; Chirici, Gherardo

2013-04-01

A correct characterization of the status and trend of forest condition is essential to support reporting processes at national and international level. An international forest condition monitoring has been implemented in Europe since 1987 under the auspices of the International Co-operative Programme on Assessment and Monitoring of Air Pollution Effects on Forests (ICP Forests). The monitoring is based on harmonized methodologies, with individual countries being responsible for its implementation. Due to inconsistencies and problems in sampling design, however, the ICP Forests network is not able to produce reliable quantitative estimates of forest condition at European and sometimes at country level. This paper proposes (1) a set of requirements for status and change assessment and (2) a harmonized sampling strategy able to provide unbiased and consistent estimators of forest condition parameters and of their changes at both country and European level. Under the assumption that a common definition of forest holds among European countries, monitoring objectives, parameters of concern and accuracy indexes are stated. On the basis of fixed-area plot sampling performed independently in each country, an unbiased and consistent estimator of forest defoliation indexes is obtained at both country and European level, together with conservative estimators of their sampling variance and power in the detection of changes. The strategy adopts a probabilistic sampling scheme based on fixed-area plots selected by means of systematic or stratified schemes. Operative guidelines for its application are provided.

Empirical Likelihood in Nonignorable Covariate-Missing Data Problems.

PubMed

Xie, Yanmei; Zhang, Biao

2017-04-20

Missing covariate data occurs often in regression analysis, which frequently arises in the health and social sciences as well as in survey sampling. We study methods for the analysis of a nonignorable covariate-missing data problem in an assumed conditional mean function when some covariates are completely observed but other covariates are missing for some subjects. We adopt the semiparametric perspective of Bartlett et al. (Improving upon the efficiency of complete case analysis when covariates are MNAR. Biostatistics 2014;15:719-30) on regression analyses with nonignorable missing covariates, in which they have introduced the use of two working models, the working probability model of missingness and the working conditional score model. In this paper, we study an empirical likelihood approach to nonignorable covariate-missing data problems with the objective of effectively utilizing the two working models in the analysis of covariate-missing data. We propose a unified approach to constructing a system of unbiased estimating equations, where there are more equations than unknown parameters of interest. One useful feature of these unbiased estimating equations is that they naturally incorporate the incomplete data into the data analysis, making it possible to seek efficient estimation of the parameter of interest even when the working regression function is not specified to be the optimal regression function. We apply the general methodology of empirical likelihood to optimally combine these unbiased estimating equations. We propose three maximum empirical likelihood estimators of the underlying regression parameters and compare their efficiencies with other existing competitors. We present a simulation study to compare the finite-sample performance of various methods with respect to bias, efficiency, and robustness to model misspecification. The proposed empirical likelihood method is also illustrated by an analysis of a data set from the US National Health and Nutrition Examination Survey (NHANES).

Ethnic Group Bias in Intelligence Test Items.

ERIC Educational Resources Information Center

Scheuneman, Janice

In previous studies of ethnic group bias in intelligence test items, the question of bias has been confounded with ability differences between the ethnic group samples compared. The present study is based on a conditional probability model in which an unbiased item is defined as one where the probability of a correct response to an item is the…

Variation in isotopologues of atmospheric nitric acid in passively collected samples along an air pollution gradient in southern California

Treesearch

Michael D. Bell; James O. Sickman; Andrzej Bytnerowicz; Pamela E. Padgett; Edith B. Allen

2014-01-01

The sources and oxidation pathways of atmospheric nitric acid (HNO3) can be evaluated using the isotopic signatures of oxygen (O) and nitrogen (N). This study evaluated the ability of Nylasorb nylon filters to passively collect unbiased isotopologues of atmospheric HNO3 under controlled and field conditions. Filters...

A statistical test of unbiased evolution of body size in birds.

PubMed

Bokma, Folmer

2002-12-01

Of the approximately 9500 bird species, the vast majority is small-bodied. That is a general feature of evolutionary lineages, also observed for instance in mammals and plants. The avian interspecific body size distribution is right-skewed even on a logarithmic scale. That has previously been interpreted as evidence that body size evolution has been biased. However, a procedure to test for unbiased evolution from the shape of body size distributions was lacking. In the present paper unbiased body size evolution is defined precisely, and a statistical test is developed based on Monte Carlo simulation of unbiased evolution. Application of the test to birds suggests that it is highly unlikely that avian body size evolution has been unbiased as defined. Several possible explanations for this result are discussed. A plausible explanation is that the general model of unbiased evolution assumes that population size and generation time do not affect the evolutionary variability of body size; that is, that micro- and macroevolution are decoupled, which theory suggests is not likely to be the case.

Mutually unbiased bases and semi-definite programming

NASA Astrophysics Data System (ADS)

Brierley, Stephen; Weigert, Stefan

2010-11-01

A complex Hilbert space of dimension six supports at least three but not more than seven mutually unbiased bases. Two computer-aided analytical methods to tighten these bounds are reviewed, based on a discretization of parameter space and on Gröbner bases. A third algorithmic approach is presented: the non-existence of more than three mutually unbiased bases in composite dimensions can be decided by a global optimization method known as semidefinite programming. The method is used to confirm that the spectral matrix cannot be part of a complete set of seven mutually unbiased bases in dimension six.

Fault Tolerant Characteristics of Artificial Neural Network Electronic Hardware

NASA Technical Reports Server (NTRS)

Zee, Frank

1995-01-01

The fault tolerant characteristics of analog-VLSI artificial neural network (with 32 neurons and 532 synapses) chips are studied by exposing them to high energy electrons, high energy protons, and gamma ionizing radiations under biased and unbiased conditions. The biased chips became nonfunctional after receiving a cumulative dose of less than 20 krads, while the unbiased chips only started to show degradation with a cumulative dose of over 100 krads. As the total radiation dose increased, all the components demonstrated graceful degradation. The analog sigmoidal function of the neuron became steeper (increase in gain), current leakage from the synapses progressively shifted the sigmoidal curve, and the digital memory of the synapses and the memory addressing circuits began to gradually fail. From these radiation experiments, we can learn how to modify certain designs of the neural network electronic hardware without using radiation-hardening techniques to increase its reliability and fault tolerance.

A comparison of selection at list time and time-stratified sampling for estimating suspended sediment loads

Treesearch

Robert B. Thomas; Jack Lewis

1993-01-01

Time-stratified sampling of sediment for estimating suspended load is introduced and compared to selection at list time (SALT) sampling. Both methods provide unbiased estimates of load and variance. The magnitude of the variance of the two methods is compared using five storm populations of suspended sediment flux derived from turbidity data. Under like conditions,...

Empirical Benchmarks of Hidden Bias in Educational Research: Implication for Assessing How well Propensity Score Methods Approximate Experiments and Conducting Sensitivity Analysis

ERIC Educational Resources Information Center

Dong, Nianbo; Lipsey, Mark

2014-01-01

When randomized control trials (RCT) are not feasible, researchers seek other methods to make causal inference, e.g., propensity score methods. One of the underlined assumptions for the propensity score methods to obtain unbiased treatment effect estimates is the ignorability assumption, that is, conditional on the propensity score, treatment…

Grade of Membership Response Time Model for Detecting Guessing Behaviors

ERIC Educational Resources Information Center

Pokropek, Artur

2016-01-01

A response model that is able to detect guessing behaviors and produce unbiased estimates in low-stake conditions using timing information is proposed. The model is a special case of the grade of membership model in which responses are modeled as partial members of a class that is affected by motivation and a class that responds only according to…

Can We Spin Straw Into Gold? An Evaluation of Immigrant Legal Status Imputation Approaches

PubMed Central

Van Hook, Jennifer; Bachmeier, James D.; Coffman, Donna; Harel, Ofer

2014-01-01

Researchers have developed logical, demographic, and statistical strategies for imputing immigrants’ legal status, but these methods have never been empirically assessed. We used Monte Carlo simulations to test whether, and under what conditions, legal status imputation approaches yield unbiased estimates of the association of unauthorized status with health insurance coverage. We tested five methods under a range of missing data scenarios. Logical and demographic imputation methods yielded biased estimates across all missing data scenarios. Statistical imputation approaches yielded unbiased estimates only when unauthorized status was jointly observed with insurance coverage; when this condition was not met, these methods overestimated insurance coverage for unauthorized relative to legal immigrants. We next showed how bias can be reduced by incorporating prior information about unauthorized immigrants. Finally, we demonstrated the utility of the best-performing statistical method for increasing power. We used it to produce state/regional estimates of insurance coverage among unauthorized immigrants in the Current Population Survey, a data source that contains no direct measures of immigrants’ legal status. We conclude that commonly employed legal status imputation approaches are likely to produce biased estimates, but data and statistical methods exist that could substantially reduce these biases. PMID:25511332

Unbiased Metabolite Profiling of Schizophrenia Fibroblasts under Stressful Perturbations Reveals Dysregulation of Plasmalogens and Phosphatidylcholines.

PubMed

Huang, Joanne H; Park, Hyoungjun; Iaconelli, Jonathan; Berkovitch, Shaunna S; Watmuff, Bradley; McPhie, Donna; Öngür, Dost; Cohen, Bruce M; Clish, Clary B; Karmacharya, Rakesh

2017-02-03

We undertook an unbiased metabolite profiling of fibroblasts from schizophrenia patients and healthy controls to identify metabolites and pathways that are dysregulated in disease, seeking to gain new insights into the disease biology of schizophrenia and to discover potential disease-related biomarkers. We measured polar and nonpolar metabolites in the fibroblasts under normal conditions and under two stressful physiological perturbations: growth in low-glucose media and exposure to the steroid hormone dexamethasone. We found that metabolites that were significantly different between schizophrenia and control subjects showed separation of the two groups by partial least-squares discriminant analysis methods. This separation between schizophrenia and healthy controls was more robust with metabolites identified under the perturbation conditions. The most significant individual metabolite differences were also found in the perturbation experiments. Metabolites that were significantly different between schizophrenia and healthy controls included a number of plasmalogens and phosphatidylcholines. We present these results in the context of previous reports of metabolic profiling of brain tissue and plasma in schizophrenia. These results show the applicability of metabolite profiling under stressful perturbations to reveal cellular pathways that may be involved in disease biology.

Unbiasedness

USGS Publications Warehouse

Link, W.A.; Armitage, Peter; Colton, Theodore

1998-01-01

Unbiasedness is probably the best known criterion for evaluating the performance of estimators. This note describes unbiasedness, demonstrating various failings of the criterion. It is shown that unbiased estimators might not exist, or might not be unique; an example of a unique but clearly unacceptable unbiased estimator is given. It is shown that unbiased estimators are not translation invariant. Various alternative criteria are described, and are illustrated through examples.

FAST TRACK COMMUNICATION: Affine constellations without mutually unbiased counterparts

NASA Astrophysics Data System (ADS)

Weigert, Stefan; Durt, Thomas

2010-10-01

It has been conjectured that a complete set of mutually unbiased bases in a space of dimension d exists if and only if there is an affine plane of order d. We introduce affine constellations and compare their existence properties with those of mutually unbiased constellations. The observed discrepancies make a deeper relation between the two existence problems unlikely.

Suitability of the line intersect method for sampling hardwood logging residues

Treesearch

A. Jeff Martin

1976-01-01

The line intersect method of sampling logging residues was tested in Appalachian hardwoods and was found to provide unbiased estimates of the volume of residue in cubic feet per acre. Thirty-two chains of sample line were established on each of sixteen 1-acre plots on cutover areas in a variety of conditions. Estimates from these samples were then compared to actual...

A validation of 11 body-condition indices in a giant snake species that exhibits positive allometry.

PubMed

Falk, Bryan G; Snow, Ray W; Reed, Robert N

2017-01-01

Body condition is a gauge of the energy stores of an animal, and though it has important implications for fitness, survival, competition, and disease, it is difficult to measure directly. Instead, body condition is frequently estimated as a body condition index (BCI) using length and mass measurements. A desirable BCI should accurately reflect true body condition and be unbiased with respect to size (i.e., mean BCI estimates should not change across different length or mass ranges), and choosing the most-appropriate BCI is not straightforward. We evaluated 11 different BCIs in 248 Burmese pythons (Python bivittatus), organisms that, like other snakes, exhibit simple body plans well characterized by length and mass. We found that the length-mass relationship in Burmese pythons is positively allometric, where mass increases rapidly with respect to length, and this allowed us to explore the effects of allometry on BCI verification. We employed three alternative measures of 'true' body condition: percent fat, scaled fat, and residual fat. The latter two measures mostly accommodated allometry in true body condition, but percent fat did not. Our inferences of the best-performing BCIs depended heavily on our measure of true body condition, with most BCIs falling into one of two groups. The first group contained most BCIs based on ratios, and these were associated with percent fat and body length (i.e., were biased). The second group contained the scaled mass index and most of the BCIs based on linear regressions, and these were associated with both scaled and residual fat but not body length (i.e., were unbiased). Our results show that potential differences in measures of true body condition should be explored in BCI verification studies, particularly in organisms undergoing allometric growth. Furthermore, the caveats of each BCI and similarities to other BCIs are important to consider when determining which BCI is appropriate for any particular taxon.

A validation of 11 body-condition indices in a giant snake species that exhibits positive allometry

USGS Publications Warehouse

Falk, Bryan; Snow, Ray W.; Reed, Robert N.

2017-01-01

Body condition is a gauge of the energy stores of an animal, and though it has important implications for fitness, survival, competition, and disease, it is difficult to measure directly. Instead, body condition is frequently estimated as a body condition index (BCI) using length and mass measurements. A desirable BCI should accurately reflect true body condition and be unbiased with respect to size (i.e., mean BCI estimates should not change across different length or mass ranges), and choosing the most-appropriate BCI is not straightforward. We evaluated 11 different BCIs in 248 Burmese pythons (Python bivittatus), organisms that, like other snakes, exhibit simple body plans well characterized by length and mass. We found that the length-mass relationship in Burmese pythons is positively allometric, where mass increases rapidly with respect to length, and this allowed us to explore the effects of allometry on BCI verification. We employed three alternative measures of ‘true’ body condition: percent fat, scaled fat, and residual fat. The latter two measures mostly accommodated allometry in true body condition, but percent fat did not. Our inferences of the best-performing BCIs depended heavily on our measure of true body condition, with most BCIs falling into one of two groups. The first group contained most BCIs based on ratios, and these were associated with percent fat and body length (i.e., were biased). The second group contained the scaled mass index and most of the BCIs based on linear regressions, and these were associated with both scaled and residual fat but not body length (i.e., were unbiased). Our results show that potential differences in measures of true body condition should be explored in BCI verification studies, particularly in organisms undergoing allometric growth. Furthermore, the caveats of each BCI and similarities to other BCIs are important to consider when determining which BCI is appropriate for any particular taxon.

Aspects of mutually unbiased bases in odd-prime-power dimensions

NASA Astrophysics Data System (ADS)

Chaturvedi, S.

2002-04-01

We rephrase the Wootters-Fields construction [W. K. Wootters and B. C. Fields, Ann. Phys. 191, 363 (1989)] of a full set of mutually unbiased bases in a complex vector space of dimensions N=pr, where p is an odd prime, in terms of the character vectors of the cyclic group G of order p. This form may be useful in explicitly writing down mutually unbiased bases for N=pr.

Unbiased estimation in seamless phase II/III trials with unequal treatment effect variances and hypothesis-driven selection rules.

PubMed

Robertson, David S; Prevost, A Toby; Bowden, Jack

2016-09-30

Seamless phase II/III clinical trials offer an efficient way to select an experimental treatment and perform confirmatory analysis within a single trial. However, combining the data from both stages in the final analysis can induce bias into the estimates of treatment effects. Methods for bias adjustment developed thus far have made restrictive assumptions about the design and selection rules followed. In order to address these shortcomings, we apply recent methodological advances to derive the uniformly minimum variance conditionally unbiased estimator for two-stage seamless phase II/III trials. Our framework allows for the precision of the treatment arm estimates to take arbitrary values, can be utilised for all treatments that are taken forward to phase III and is applicable when the decision to select or drop treatment arms is driven by a multiplicity-adjusted hypothesis testing procedure. © 2016 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd. © 2016 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd.

Efficient Determination of Free Energy Landscapes in Multiple Dimensions from Biased Umbrella Sampling Simulations Using Linear Regression.

PubMed

Meng, Yilin; Roux, Benoît

2015-08-11

The weighted histogram analysis method (WHAM) is a standard protocol for postprocessing the information from biased umbrella sampling simulations to construct the potential of mean force with respect to a set of order parameters. By virtue of the WHAM equations, the unbiased density of state is determined by satisfying a self-consistent condition through an iterative procedure. While the method works very effectively when the number of order parameters is small, its computational cost grows rapidly in higher dimension. Here, we present a simple and efficient alternative strategy, which avoids solving the self-consistent WHAM equations iteratively. An efficient multivariate linear regression framework is utilized to link the biased probability densities of individual umbrella windows and yield an unbiased global free energy landscape in the space of order parameters. It is demonstrated with practical examples that free energy landscapes that are comparable in accuracy to WHAM can be generated at a small fraction of the cost.

Efficient Determination of Free Energy Landscapes in Multiple Dimensions from Biased Umbrella Sampling Simulations Using Linear Regression

PubMed Central

2015-01-01

The weighted histogram analysis method (WHAM) is a standard protocol for postprocessing the information from biased umbrella sampling simulations to construct the potential of mean force with respect to a set of order parameters. By virtue of the WHAM equations, the unbiased density of state is determined by satisfying a self-consistent condition through an iterative procedure. While the method works very effectively when the number of order parameters is small, its computational cost grows rapidly in higher dimension. Here, we present a simple and efficient alternative strategy, which avoids solving the self-consistent WHAM equations iteratively. An efficient multivariate linear regression framework is utilized to link the biased probability densities of individual umbrella windows and yield an unbiased global free energy landscape in the space of order parameters. It is demonstrated with practical examples that free energy landscapes that are comparable in accuracy to WHAM can be generated at a small fraction of the cost. PMID:26574437

Dynamic properties of molecular motors in burnt-bridge models

NASA Astrophysics Data System (ADS)

Artyomov, Maxim N.; Morozov, Alexander Yu; Pronina, Ekaterina; Kolomeisky, Anatoly B.

2007-08-01

Dynamic properties of molecular motors that fuel their motion by actively interacting with underlying molecular tracks are studied theoretically via discrete-state stochastic 'burnt-bridge' models. The transport of the particles is viewed as an effective diffusion along one-dimensional lattices with periodically distributed weak links. When an unbiased random walker passes the weak link it can be destroyed ('burned') with probability p, providing a bias in the motion of the molecular motor. We present a theoretical approach that allows one to calculate exactly all dynamic properties of motor proteins, such as velocity and dispersion, under general conditions. It is found that dispersion is a decreasing function of the concentration of bridges, while the dependence of dispersion on the burning probability is more complex. Our calculations also show a gap in dispersion for very low concentrations of weak links or for very low burning probabilities which indicates a dynamic phase transition between unbiased and biased diffusion regimes. Theoretical findings are supported by Monte Carlo computer simulations.

Comparative modeling and benchmarking data sets for human histone deacetylases and sirtuin families.

PubMed

Xia, Jie; Tilahun, Ermias Lemma; Kebede, Eyob Hailu; Reid, Terry-Elinor; Zhang, Liangren; Wang, Xiang Simon

2015-02-23

Histone deacetylases (HDACs) are an important class of drug targets for the treatment of cancers, neurodegenerative diseases, and other types of diseases. Virtual screening (VS) has become fairly effective approaches for drug discovery of novel and highly selective histone deacetylase inhibitors (HDACIs). To facilitate the process, we constructed maximal unbiased benchmarking data sets for HDACs (MUBD-HDACs) using our recently published methods that were originally developed for building unbiased benchmarking sets for ligand-based virtual screening (LBVS). The MUBD-HDACs cover all four classes including Class III (Sirtuins family) and 14 HDAC isoforms, composed of 631 inhibitors and 24609 unbiased decoys. Its ligand sets have been validated extensively as chemically diverse, while the decoy sets were shown to be property-matching with ligands and maximal unbiased in terms of "artificial enrichment" and "analogue bias". We also conducted comparative studies with DUD-E and DEKOIS 2.0 sets against HDAC2 and HDAC8 targets and demonstrate that our MUBD-HDACs are unique in that they can be applied unbiasedly to both LBVS and SBVS approaches. In addition, we defined a novel metric, i.e. NLBScore, to detect the "2D bias" and "LBVS favorable" effect within the benchmarking sets. In summary, MUBD-HDACs are the only comprehensive and maximal-unbiased benchmark data sets for HDACs (including Sirtuins) that are available so far. MUBD-HDACs are freely available at http://www.xswlab.org/ .

The behaviour of random forest permutation-based variable importance measures under predictor correlation.

PubMed

Nicodemus, Kristin K; Malley, James D; Strobl, Carolin; Ziegler, Andreas

2010-02-27

Random forests (RF) have been increasingly used in applications such as genome-wide association and microarray studies where predictor correlation is frequently observed. Recent works on permutation-based variable importance measures (VIMs) used in RF have come to apparently contradictory conclusions. We present an extended simulation study to synthesize results. In the case when both predictor correlation was present and predictors were associated with the outcome (HA), the unconditional RF VIM attributed a higher share of importance to correlated predictors, while under the null hypothesis that no predictors are associated with the outcome (H0) the unconditional RF VIM was unbiased. Conditional VIMs showed a decrease in VIM values for correlated predictors versus the unconditional VIMs under HA and was unbiased under H0. Scaled VIMs were clearly biased under HA and H0. Unconditional unscaled VIMs are a computationally tractable choice for large datasets and are unbiased under the null hypothesis. Whether the observed increased VIMs for correlated predictors may be considered a "bias" - because they do not directly reflect the coefficients in the generating model - or if it is a beneficial attribute of these VIMs is dependent on the application. For example, in genetic association studies, where correlation between markers may help to localize the functionally relevant variant, the increased importance of correlated predictors may be an advantage. On the other hand, we show examples where this increased importance may result in spurious signals.

Quantitative Assessment of In-solution Digestion Efficiency Identifies Optimal Protocols for Unbiased Protein Analysis*

PubMed Central

León, Ileana R.; Schwämmle, Veit; Jensen, Ole N.; Sprenger, Richard R.

2013-01-01

The majority of mass spectrometry-based protein quantification studies uses peptide-centric analytical methods and thus strongly relies on efficient and unbiased protein digestion protocols for sample preparation. We present a novel objective approach to assess protein digestion efficiency using a combination of qualitative and quantitative liquid chromatography-tandem MS methods and statistical data analysis. In contrast to previous studies we employed both standard qualitative as well as data-independent quantitative workflows to systematically assess trypsin digestion efficiency and bias using mitochondrial protein fractions. We evaluated nine trypsin-based digestion protocols, based on standard in-solution or on spin filter-aided digestion, including new optimized protocols. We investigated various reagents for protein solubilization and denaturation (dodecyl sulfate, deoxycholate, urea), several trypsin digestion conditions (buffer, RapiGest, deoxycholate, urea), and two methods for removal of detergents before analysis of peptides (acid precipitation or phase separation with ethyl acetate). Our data-independent quantitative liquid chromatography-tandem MS workflow quantified over 3700 distinct peptides with 96% completeness between all protocols and replicates, with an average 40% protein sequence coverage and an average of 11 peptides identified per protein. Systematic quantitative and statistical analysis of physicochemical parameters demonstrated that deoxycholate-assisted in-solution digestion combined with phase transfer allows for efficient, unbiased generation and recovery of peptides from all protein classes, including membrane proteins. This deoxycholate-assisted protocol was also optimal for spin filter-aided digestions as compared with existing methods. PMID:23792921

Impact of using scatterometer and altimeter data on storm surge forecasting

NASA Astrophysics Data System (ADS)

Bajo, Marco; De Biasio, Francesco; Umgiesser, Georg; Vignudelli, Stefano; Zecchetto, Stefano

2017-05-01

Satellite data are rarely used in storm surge models because of the lack of established methodologies. Nevertheless, they can provide useful information on surface wind and sea level, which can potentially improve the forecast. In this paper satellite wind data are used to correct the bias of wind originating from a global atmospheric model, while satellite sea level data are used to improve the initial conditions of the model simulations. In a first step, the capability of global winds (biased and unbiased) to adequately force a storm surge model are assessed against that of a high resolution local wind. Then, the added value of direct assimilation of satellite altimeter data in the storm surge model is tested. Eleven storm surge events, recorded in Venice from 2008 to 2012, are simulated using different configurations of wind forcing and altimeter data assimilation. Focusing on the maximum surge peak, results show that the relative error, averaged over the eleven cases considered, decreases from 13% to 7%, using both the unbiased wind and assimilating the altimeter data, while, if the high resolution local wind is used to force the hydrodynamic model, the altimeter data assimilation reduces the error from 9% to 6%. Yet, the overall capabilities in reproducing the surge in the first day of forecast, measured by the correlation and by the rms error, improve only with the use of the unbiased global wind and not with the use of high resolution local wind and altimeter data assimilation.

The influence of cooperation and defection on social decision making in depression: A study of the iterated Prisoner's Dilemma Game.

PubMed

Sorgi, Kristen M; van 't Wout, Mascha

2016-12-30

This study evaluated the influence of self-reported levels of depression on interpersonal strategic decision making when interacting with partners who differed in their predetermined tendency to cooperate in three separate computerized iterated Prisoner's Dilemma Games (iPDGs). Across 29 participants, cooperation was lowest when interacting with a predominantly defecting partner and highest when interacting with a predominantly cooperating partner. Greater depression severity was related to steadier and continued cooperation over trials with the cooperating partner, seeming to reflect a prosocial response tendency when interacting with this partner. With the unbiased partner, depression severity was associated with a more volatile response pattern in reaction to cooperation and defection by this partner. Severity of depression did not influence cooperation with a defecting partner or expectations about partner cooperation reported before the task began. Taken together, these data appear to show that in predominately positive interactions, as in the cooperating partner condition, depression is associated with less volatile, more consistent cooperation. When such clear feedback is absent, as in the unbiased partner condition, depression is associated with more volatile behavior. Nonetheless, participants were generally able to adapt their behavior accordingly in this dynamic interpersonal decision making context. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Hierarchical thinking in network biology: the unbiased modularization of biochemical networks.

PubMed

Papin, Jason A; Reed, Jennifer L; Palsson, Bernhard O

2004-12-01

As reconstructed biochemical reaction networks continue to grow in size and scope, there is a growing need to describe the functional modules within them. Such modules facilitate the study of biological processes by deconstructing complex biological networks into conceptually simple entities. The definition of network modules is often based on intuitive reasoning. As an alternative, methods are being developed for defining biochemical network modules in an unbiased fashion. These unbiased network modules are mathematically derived from the structure of the whole network under consideration.

Rényi and Tsallis formulations of separability conditions in finite dimensions

NASA Astrophysics Data System (ADS)

Rastegin, Alexey E.

2017-12-01

Separability conditions for a bipartite quantum system of finite-dimensional subsystems are formulated in terms of Rényi and Tsallis entropies. Entropic uncertainty relations often lead to entanglement criteria. We propose new approach based on the convolution of discrete probability distributions. Measurements on a total system are constructed of local ones according to the convolution scheme. Separability conditions are derived on the base of uncertainty relations of the Maassen-Uffink type as well as majorization relations. On each of subsystems, we use a pair of sets of subnormalized vectors that form rank-one POVMs. We also obtain entropic separability conditions for local measurements with a special structure, such as mutually unbiased bases and symmetric informationally complete measurements. The relevance of the derived separability conditions is demonstrated with several examples.

Comparative Modeling and Benchmarking Data Sets for Human Histone Deacetylases and Sirtuin Families

PubMed Central

Xia, Jie; Tilahun, Ermias Lemma; Kebede, Eyob Hailu; Reid, Terry-Elinor; Zhang, Liangren; Wang, Xiang Simon

2015-01-01

Histone Deacetylases (HDACs) are an important class of drug targets for the treatment of cancers, neurodegenerative diseases and other types of diseases. Virtual screening (VS) has become fairly effective approaches for drug discovery of novel and highly selective Histone Deacetylases Inhibitors (HDACIs). To facilitate the process, we constructed the Maximal Unbiased Benchmarking Data Sets for HDACs (MUBD-HDACs) using our recently published methods that were originally developed for building unbiased benchmarking sets for ligand-based virtual screening (LBVS). The MUBD-HDACs covers all 4 Classes including Class III (Sirtuins family) and 14 HDACs isoforms, composed of 631 inhibitors and 24,609 unbiased decoys. Its ligand sets have been validated extensively as chemically diverse, while the decoy sets were shown to be property-matching with ligands and maximal unbiased in terms of “artificial enrichment” and “analogue bias”. We also conducted comparative studies with DUD-E and DEKOIS 2.0 sets against HDAC2 and HDAC8 targets, and demonstrate that our MUBD-HDACs is unique in that it can be applied unbiasedly to both LBVS and SBVS approaches. In addition, we defined a novel metric, i.e. NLBScore, to detect the “2D bias” and “LBVS favorable” effect within the benchmarking sets. In summary, MUBD-HDACs is the only comprehensive and maximal-unbiased benchmark data sets for HDACs (including Sirtuins) that is available so far. MUBD-HDACs is freely available at http://www.xswlab.org/. PMID:25633490

An Unbiased Estimator of Gene Diversity with Improved Variance for Samples Containing Related and Inbred Individuals of any Ploidy

PubMed Central

Harris, Alexandre M.; DeGiorgio, Michael

2016-01-01

Gene diversity, or expected heterozygosity (H), is a common statistic for assessing genetic variation within populations. Estimation of this statistic decreases in accuracy and precision when individuals are related or inbred, due to increased dependence among allele copies in the sample. The original unbiased estimator of expected heterozygosity underestimates true population diversity in samples containing relatives, as it only accounts for sample size. More recently, a general unbiased estimator of expected heterozygosity was developed that explicitly accounts for related and inbred individuals in samples. Though unbiased, this estimator’s variance is greater than that of the original estimator. To address this issue, we introduce a general unbiased estimator of gene diversity for samples containing related or inbred individuals, which employs the best linear unbiased estimator of allele frequencies, rather than the commonly used sample proportion. We examine the properties of this estimator, H∼BLUE, relative to alternative estimators using simulations and theoretical predictions, and show that it predominantly has the smallest mean squared error relative to others. Further, we empirically assess the performance of H∼BLUE on a global human microsatellite dataset of 5795 individuals, from 267 populations, genotyped at 645 loci. Additionally, we show that the improved variance of H∼BLUE leads to improved estimates of the population differentiation statistic, FST, which employs measures of gene diversity within its calculation. Finally, we provide an R script, BestHet, to compute this estimator from genomic and pedigree data. PMID:28040781

Quantification of Cysteinyl-S-Nitrosylation by Fluorescence in Unbiased Proteomic Studies*

PubMed Central

Wiktorowicz, John E.; Stafford, Susan; Rea, Harriet; Urvil, Petri; Soman, Kizhake; Kurosky, Alexander; Perez-Polo, J. Regino; Savidge, Tor C.

2011-01-01

Cysteinyl-S-nitrosylation has emerged as an important post-translational modification affecting protein function in health and disease. Great emphasis has been placed on global, unbiased quantification of S-nitrosylated proteins due to physiologic and oxidative stimuli. However, current strategies have been hampered by sample loss and altered protein electrophoretic mobility. Here, we describe a novel quantitative approach that combines accurate, sensitive fluorescence modification of cysteine S-nitrosylation that leaves electrophoretic mobility unaffected (SNOFlo), and introduce unique concepts for measuring changes in S-nitrosylation status relative to protein abundance. Its efficacy in defining the functional S-nitrosoproteome is demonstrated in two diverse biological applications: an in vivo rat hypoxia-ischemia reperfusion model, and antimicrobial S-nitrosoglutathione-driven transnitrosylation of an enteric microbial pathogen. The suitability of this approach for investigating endogenous S-nitrosylation is further demonstrated using Ingenuity Pathways analysis that identified nervous system and cellular development networks as the top two networks. Functional analysis of differentially S-nitrosylated proteins indicated their involvement in apoptosis, branching morphogenesis of axons, cortical neurons, and sympathetic neurites, neurogenesis, and calcium signaling. Major abundance changes were also observed for fibrillar proteins known to be stress-responsive in neurons and glia. Thus, both examples demonstrate the technique’s power in confirming the widespread involvement of S-nitrosylation in hypoxia-ischemia/reperfusion injury and in antimicrobial host responses. PMID:21615140

An examination of effect estimation in factorial and standardly-tailored designs

PubMed Central

Allore, Heather G; Murphy, Terrence E

2012-01-01

Background Many clinical trials are designed to test an intervention arm against a control arm wherein all subjects are equally eligible for all interventional components. Factorial designs have extended this to test multiple intervention components and their interactions. A newer design referred to as a ‘standardly-tailored’ design, is a multicomponent interventional trial that applies individual interventional components to modify risk factors identified a priori and tests whether health outcomes differ between treatment arms. Standardly-tailored designs do not require that all subjects be eligible for every interventional component. Although standardly-tailored designs yield an estimate for the net effect of the multicomponent intervention, it has not yet been shown if they permit separate, unbiased estimation of individual component effects. The ability to estimate the most potent interventional components has direct bearing on conducting second stage translational research. Purpose We present statistical issues related to the estimation of individual component effects in trials of geriatric conditions using factorial and standardly-tailored designs. The medical community is interested in second stage translational research involving the transfer of results from a randomized clinical trial to a community setting. Before such research is undertaken, main effects and synergistic and or antagonistic interactions between them should be identified. Knowledge of the relative strength and direction of the effects of the individual components and their interactions facilitates the successful transfer of clinically significant findings and may potentially reduce the number of interventional components needed. Therefore the current inability of the standardly-tailored design to provide unbiased estimates of individual interventional components is a serious limitation in their applicability to second stage translational research. Methods We discuss estimation of individual component effects from the family of factorial designs and this limitation for standardly-tailored designs. We use the phrase ‘factorial designs’ to describe full-factorial designs and their derivatives including the fractional factorial, partial factorial, incomplete factorial and modified reciprocal designs. We suggest two potential directions for designing multicomponent interventions to facilitate unbiased estimates of individual interventional components. Results Full factorial designs and their variants are the most common multicomponent trial design described in the literature and differ meaningfully from standardly-tailored designs. Factorial and standardly-tailored designs result in similar estimates of net effect with different levels of precision. Unbiased estimation of individual component effects from a standardly-tailored design will require new methodology. Limitations Although clinically relevant in geriatrics, previous applications of standardly-tailored designs have not provided unbiased estimates of the effects of individual interventional components. Discussion Future directions to estimate individual component effects from standardly-tailored designs include applying D-optimal designs and creating independent linear combinations of risk factors analogous to factor analysis. Conclusion Methods are needed to extract unbiased estimates of the effects of individual interventional components from standardly-tailored designs. PMID:18375650

The effects of AMPA receptor blockade in the prelimbic cortex on systemic and ventral tegmental area opiate reward sensitivity.

PubMed

De Jaeger, Xavier; Bishop, Stephanie F; Ahmad, Tasha; Lyons, Danika; Ng, Garye Ami; Laviolette, Steven R

2013-02-01

The medial prefrontal cortex (mPFC) is a key neural region involved in opiate-related reward memory processing. AMPA receptor transmission in the mPFC modulates opiate-related reward memory processing, and chronic opiate exposure is associated with alterations in intra-mPFC AMPA receptor function. The objectives of this study were to examine how pharmacological blockade of AMPA receptor transmission in the prelimbic (PLC) division of the mPFC may modulate opiate reward memory acquisition and whether opiate exposure state may modulate the functional role of intra-PLC AMPA receptor transmission during opiate reward learning. Using an unbiased conditioned place preference (CPP) procedure in rats, we performed discrete, bilateral intra-PLC microinfusions of the AMPA receptor antagonist, 6,7-dinitroquinoxaline-2,3-dione, prior to behavioral morphine CPP conditioning, using sub-reward threshold conditioning doses of either systemic (0.05 mg/kg; i.p.) or intra-ventral tegmental area (VTA) morphine (250 ng/0.5 μl). We show that, in both opiate-naïve and opiate-dependent states, intra-PLC blockade of AMPA receptor transmission, but not the infralimbic cortex, increases the behavioral reward magnitude of systemic or intra-VTA morphine. This effect is dependent on dopamine (DA)ergic signaling because pre-administration of cis-(Z)-flupenthixol-dihydrochloride (α-flu), a broad-spectrum dopamine receptor antagonist, blocked the morphine-reward potentiating effects of AMPA receptor blockade. These findings suggest a critical role for intra-PLC AMPA receptor transmission in the processing of opiate reward signaling. Furthermore, blockade of AMPA transmission specifically within the PLC is capable of switching opiate reward processing to a DA-dependent reward system, independently of previous opiate exposure history.

Shrinkage covariance matrix approach based on robust trimmed mean in gene sets detection

NASA Astrophysics Data System (ADS)

Karjanto, Suryaefiza; Ramli, Norazan Mohamed; Ghani, Nor Azura Md; Aripin, Rasimah; Yusop, Noorezatty Mohd

2015-02-01

Microarray involves of placing an orderly arrangement of thousands of gene sequences in a grid on a suitable surface. The technology has made a novelty discovery since its development and obtained an increasing attention among researchers. The widespread of microarray technology is largely due to its ability to perform simultaneous analysis of thousands of genes in a massively parallel manner in one experiment. Hence, it provides valuable knowledge on gene interaction and function. The microarray data set typically consists of tens of thousands of genes (variables) from just dozens of samples due to various constraints. Therefore, the sample covariance matrix in Hotelling's T2 statistic is not positive definite and become singular, thus it cannot be inverted. In this research, the Hotelling's T2 statistic is combined with a shrinkage approach as an alternative estimation to estimate the covariance matrix to detect significant gene sets. The use of shrinkage covariance matrix overcomes the singularity problem by converting an unbiased to an improved biased estimator of covariance matrix. Robust trimmed mean is integrated into the shrinkage matrix to reduce the influence of outliers and consequently increases its efficiency. The performance of the proposed method is measured using several simulation designs. The results are expected to outperform existing techniques in many tested conditions.

Spectroscopic observation of SN2017gkk by NUTS (NOT Un-biased Transient Survey)

NASA Astrophysics Data System (ADS)

Onori, F.; Benetti, S.; Cappellaro, E.; Losada, Illa R.; Gafton, E.; NUTS Collaboration

2017-09-01

The Nordic Optical Telescope (NOT) Unbiased Transient Survey (NUTS; ATel #8992) reports the spectroscopic classification of supernova SN2017gkk (=MASTER OT J091344.71762842.5) in host galaxy NGC 2748.

Spectroscopic observation of ASASSN-17he by NUTS (NOT Un-biased Transient Survey)

NASA Astrophysics Data System (ADS)

Kostrzewa-Rutkowska, Z.; Benetti, S.; Dong, S.; Stritzinger, M.; Stanek, K.; Brimacombe, J.; Sagues, A.; Galindo, P.; Losada, I. Rivero

2017-10-01

The Nordic Optical Telescope (NOT) Unbiased Transient Survey (NUTS; ATel #8992) reports the spectroscopic classification of ASASSN-17he. The candidate was discovered by by the All-Sky Automated Survey for Supernovae.

Convergence of Free Energy Profile of Coumarin in Lipid Bilayer

PubMed Central

2012-01-01

Atomistic molecular dynamics (MD) simulations of druglike molecules embedded in lipid bilayers are of considerable interest as models for drug penetration and positioning in biological membranes. Here we analyze partitioning of coumarin in dioleoylphosphatidylcholine (DOPC) bilayer, based on both multiple, unbiased 3 μs MD simulations (total length) and free energy profiles along the bilayer normal calculated by biased MD simulations (∼7 μs in total). The convergences in time of free energy profiles calculated by both umbrella sampling and z-constraint techniques are thoroughly analyzed. Two sets of starting structures are also considered, one from unbiased MD simulation and the other from “pulling” coumarin along the bilayer normal. The structures obtained by pulling simulation contain water defects on the lipid bilayer surface, while those acquired from unbiased simulation have no membrane defects. The free energy profiles converge more rapidly when starting frames from unbiased simulations are used. In addition, z-constraint simulation leads to more rapid convergence than umbrella sampling, due to quicker relaxation of membrane defects. Furthermore, we show that the choice of RESP, PRODRG, or Mulliken charges considerably affects the resulting free energy profile of our model drug along the bilayer normal. We recommend using z-constraint biased MD simulations based on starting geometries acquired from unbiased MD simulations for efficient calculation of convergent free energy profiles of druglike molecules along bilayer normals. The calculation of free energy profile should start with an unbiased simulation, though the polar molecules might need a slow pulling afterward. Results obtained with the recommended simulation protocol agree well with available experimental data for two coumarin derivatives. PMID:22545027

Convergence of Free Energy Profile of Coumarin in Lipid Bilayer.

PubMed

Paloncýová, Markéta; Berka, Karel; Otyepka, Michal

2012-04-10

Atomistic molecular dynamics (MD) simulations of druglike molecules embedded in lipid bilayers are of considerable interest as models for drug penetration and positioning in biological membranes. Here we analyze partitioning of coumarin in dioleoylphosphatidylcholine (DOPC) bilayer, based on both multiple, unbiased 3 μs MD simulations (total length) and free energy profiles along the bilayer normal calculated by biased MD simulations (∼7 μs in total). The convergences in time of free energy profiles calculated by both umbrella sampling and z-constraint techniques are thoroughly analyzed. Two sets of starting structures are also considered, one from unbiased MD simulation and the other from "pulling" coumarin along the bilayer normal. The structures obtained by pulling simulation contain water defects on the lipid bilayer surface, while those acquired from unbiased simulation have no membrane defects. The free energy profiles converge more rapidly when starting frames from unbiased simulations are used. In addition, z-constraint simulation leads to more rapid convergence than umbrella sampling, due to quicker relaxation of membrane defects. Furthermore, we show that the choice of RESP, PRODRG, or Mulliken charges considerably affects the resulting free energy profile of our model drug along the bilayer normal. We recommend using z-constraint biased MD simulations based on starting geometries acquired from unbiased MD simulations for efficient calculation of convergent free energy profiles of druglike molecules along bilayer normals. The calculation of free energy profile should start with an unbiased simulation, though the polar molecules might need a slow pulling afterward. Results obtained with the recommended simulation protocol agree well with available experimental data for two coumarin derivatives.

The cannabinoid receptor 2 agonist, β-caryophyllene, reduced voluntary alcohol intake and attenuated ethanol-induced place preference and sensitivity in mice.

PubMed

Al Mansouri, Shamma; Ojha, Shreesh; Al Maamari, Elyazia; Al Ameri, Mouza; Nurulain, Syed M; Bahi, Amine

2014-09-01

Several recent studies have suggested that brain CB2 cannabinoid receptors play a major role in alcohol reward. In fact, the implication of cannabinoid neurotransmission in the reinforcing effects of ethanol (EtOH) is becoming increasingly evident. The CB2 receptor agonist, β-caryophyllene (BCP) was used to investigate the role of the CB2 receptors in mediating alcohol intake and ethanol-induced conditioned place preference (EtOH-CPP) and sensitivity in mice. The effect of BCP on alcohol intake was evaluated using the standard two-bottle choice drinking method. The mice were presented with increasing EtOH concentrations and its consumption was measured daily. Consumption of saccharin and quinine solutions was measured following the EtOH preference tests. Finally, the effect of BCP on alcohol reward and sensitivity was tested using an unbiased EtOH-CPP and loss of righting-reflex (LORR) procedures, respectively. BCP dose-dependently decreased alcohol consumption and preference. Additionally, BCP-injected mice did not show any difference from vehicle mice in total fluid intake in a 24-hour paradigm nor in their intake of graded concentrations of saccharin or quinine, suggesting that the CB2 receptor activation did not alter taste function. More importantly, BCP inhibited EtOH-CPP acquisition and exacerbated LORR duration. Interestingly, these effects were abrogated when mice were pre-injected with a selective CB2 receptor antagonist, AM630. Overall, the CB2 receptor system appears to be involved in alcohol dependence and sensitivity and may represent a potential pharmacological target for the treatment of alcoholism. Copyright © 2014 Elsevier Inc. All rights reserved.

Spectroscopic classification of Gaia18adv by NUTS (NOT Un-biased Transient Survey)

NASA Astrophysics Data System (ADS)

Gall, C.; Benetti, S.; Wyrzykowski, L.; Stritzinger, M.; Holmbo, S.; Dong, S.; Siltala, Lauri; NUTS Collaboration

2018-01-01

The Nordic Optical Telescope (NOT) Unbiased Transient Survey (NUTS; ATel #8992) collaboration reports the spectroscopic classification of Gaia18adv (SN2018hh) near the host galaxy SDSS J121341.37+282640.0.

Statistical Properties of Maximum Likelihood Estimators of Power Law Spectra Information

NASA Technical Reports Server (NTRS)

Howell, L. W.

2002-01-01

A simple power law model consisting of a single spectral index, a is believed to be an adequate description of the galactic cosmic-ray (GCR) proton flux at energies below 10(exp 13) eV, with a transition at the knee energy, E(sub k), to a steeper spectral index alpha(sub 2) greater than alpha(sub 1) above E(sub k). The Maximum likelihood (ML) procedure was developed for estimating the single parameter alpha(sub 1) of a simple power law energy spectrum and generalized to estimate the three spectral parameters of the broken power law energy spectrum from simulated detector responses and real cosmic-ray data. The statistical properties of the ML estimator were investigated and shown to have the three desirable properties: (P1) consistency (asymptotically unbiased). (P2) efficiency asymptotically attains the Cramer-Rao minimum variance bound), and (P3) asymptotically normally distributed, under a wide range of potential detector response functions. Attainment of these properties necessarily implies that the ML estimation procedure provides the best unbiased estimator possible. While simulation studies can easily determine if a given estimation procedure provides an unbiased estimate of the spectra information, and whether or not the estimator is approximately normally distributed, attainment of the Cramer-Rao bound (CRB) can only he ascertained by calculating the CRB for an assumed energy spectrum-detector response function combination, which can be quite formidable in practice. However. the effort in calculating the CRB is very worthwhile because it provides the necessary means to compare the efficiency of competing estimation techniques and, furthermore, provides a stopping rule in the search for the best unbiased estimator. Consequently, the CRB for both the simple and broken power law energy spectra are derived herein and the conditions under which they are attained in practice are investigated. The ML technique is then extended to estimate spectra information from an arbitrary number of astrophysics data sets produced by vastly different science instruments. This theory and its successful implementation will facilitate the interpretation of spectral information from multiple astrophysics missions and thereby permit the derivation of superior spectral parameter estimates based on the combination of data sets.

Birth Origin Differentially Affects Depressive-Like Behaviours: Are Captive-Born Cynomolgus Monkeys More Vulnerable to Depression than Their Wild-Born Counterparts?

PubMed Central

Camus, Sandrine MJ.; Rochais, Céline; Blois-Heulin, Catherine; Li, Qin; Hausberger, Martine; Bezard, Erwan

2013-01-01

Background Adverse early-life experience might lead to the expression of abnormal behaviours in animals and the predisposition to psychiatric disorder (e.g. major depressive disorder) in Humans. Common breeding processes employ weaning and housing conditions different from what happens in the wild. Methods The present study, therefore, investigated whether birth origin impacts the possible existence of spontaneous atypical/abnormal behaviours displayed by 40 captive-born and 40 wild-born socially-housed cynomolgus macaques in farming conditions using an unbiased ethological scan-sampling analysis followed by multifactorial correspondence and hierarchical clustering analyses. Results We identified 10 distinct profiles (groups A to J) that significantly differed on several behaviours, body postures, body orientations, distances between individuals and locations in the cage. Data suggest that 4 captive-born and 1 wild-born animals (groups G and J) present depressive-like symptoms, unnatural early life events thereby increasing the risk of developing pathological symptoms. General differences were also highlighted between the captive- and wild-born populations, implying the expression of differential coping mechanisms in response to the same captive environment. Conclusions Birth origin thus impacts the development of atypical ethologically-defined behavioural profiles, reminiscent of certain depressive-like symptoms. The use of unbiased behavioural observations might allow the identification of animal models of human mental/behavioural disorders and their most appropriate control groups. PMID:23861787

Spectroscopic classification of supernovae SN 2018aei and SN 2018aej by NUTS (NOT Un-biased Transient Survey)

NASA Astrophysics Data System (ADS)

Cannizzaro, G.; Kuncarayakti, H.; Fraser, M.; Hamanowicz, A.; Jonker, P.; Kankare, E.; Kostrzewa-Rutkowska, Z.; Onori, F.; Wevers, T.; Wyrzykowski, L.; Galbany, L.

2018-03-01

The NOT Unbiased Transient Survey (NUTS; ATel #8992) collaboration reports the spectroscopic classification of supernovae SN 2018aei and SN 2018aej, discovered by PanSTARSS Survey for Transients (ATel #11408).

Reconfigurable generation and measurement of mutually unbiased bases for time-bin qudits

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lukens, Joseph M.; Islam, Nurul T.; Lim, Charles Ci Wen

Here, we propose a method for implementing mutually unbiased generation and measurement of time-bin qudits using a cascade of electro-optic phase modulator–coded fiber Bragg grating pairs. Our approach requires only a single spatial mode and can switch rapidly between basis choices. We obtain explicit solutions for dimensions d = 2, 3, and 4 that realize all d + 1 possible mutually unbiased bases and analyze the performance of our approach in quantum key distribution. Given its practicality and compatibility with current technology, our approach provides a promising springboard for scalable processing of high-dimensional time-bin states.

Reconfigurable generation and measurement of mutually unbiased bases for time-bin qudits

DOE PAGES

Lukens, Joseph M.; Islam, Nurul T.; Lim, Charles Ci Wen; ...

2018-03-12

Here, we propose a method for implementing mutually unbiased generation and measurement of time-bin qudits using a cascade of electro-optic phase modulator–coded fiber Bragg grating pairs. Our approach requires only a single spatial mode and can switch rapidly between basis choices. We obtain explicit solutions for dimensions d = 2, 3, and 4 that realize all d + 1 possible mutually unbiased bases and analyze the performance of our approach in quantum key distribution. Given its practicality and compatibility with current technology, our approach provides a promising springboard for scalable processing of high-dimensional time-bin states.

Reconfigurable generation and measurement of mutually unbiased bases for time-bin qudits

NASA Astrophysics Data System (ADS)

Lukens, Joseph M.; Islam, Nurul T.; Lim, Charles Ci Wen; Gauthier, Daniel J.

2018-03-01

We propose a method for implementing mutually unbiased generation and measurement of time-bin qudits using a cascade of electro-optic phase modulator-coded fiber Bragg grating pairs. Our approach requires only a single spatial mode and can switch rapidly between basis choices. We obtain explicit solutions for dimensions d = 2, 3, and 4 that realize all d + 1 possible mutually unbiased bases and analyze the performance of our approach in quantum key distribution. Given its practicality and compatibility with current technology, our approach provides a promising springboard for scalable processing of high-dimensional time-bin states.

Examinations of tRNA Range of Motion Using Simulations of Cryo-EM Microscopy and X-Ray Data.

PubMed

Caulfield, Thomas R; Devkota, Batsal; Rollins, Geoffrey C

2011-01-01

We examined tRNA flexibility using a combination of steered and unbiased molecular dynamics simulations. Using Maxwell's demon algorithm, molecular dynamics was used to steer X-ray structure data toward that from an alternative state obtained from cryogenic-electron microscopy density maps. Thus, we were able to fit X-ray structures of tRNA onto cryogenic-electron microscopy density maps for hybrid states of tRNA. Additionally, we employed both Maxwell's demon molecular dynamics simulations and unbiased simulation methods to identify possible ribosome-tRNA contact areas where the ribosome may discriminate tRNAs during translation. Herein, we collected >500 ns of simulation data to assess the global range of motion for tRNAs. Biased simulations can be used to steer between known conformational stop points, while unbiased simulations allow for a general testing of conformational space previously unexplored. The unbiased molecular dynamics data describes the global conformational changes of tRNA on a sub-microsecond time scale for comparison with steered data. Additionally, the unbiased molecular dynamics data was used to identify putative contacts between tRNA and the ribosome during the accommodation step of translation. We found that the primary contact regions were H71 and H92 of the 50S subunit and ribosomal proteins L14 and L16.

Spectroscopic observation of SN 2017jzp and SN 2018bf by NUTS (NOT Un-biased Transient Survey)

NASA Astrophysics Data System (ADS)

Kuncarayakti, H.; Mattila, S.; Kotak, R.; Harmanen, J.; Reynolds, T.; Wyrzykowski, L.; Stritzinger, M.; Onori, F.; Somero, A.; Kangas, T.; Lundqvist, P.; Taddia, F.; Ergon, M.

2018-01-01

The Nordic Optical Telescope (NOT) Unbiased Transient Survey (NUTS; ATel #8992) reports the spectroscopic classification of SNe 2017jzp and 2018bf in host galaxies KUG 1326+679 and SDSS J225746.53+253833.5, respectively.

Spectroscopic observation of ASASSN-17nb and CSS170922:172546+342249 by NUTS (NOT Un-biased Transient Survey)

NASA Astrophysics Data System (ADS)

Harmanen, J.; Mattila, S.; Kuncarayakti, H.; Reynolds, T.; Somero, A.; Kangas, T.; Lundqvist, P.; Taddia, F.; Ergon, M.; Dong, S.; Pastorello, A.; Pursimo, T.; NUTS Collaboration

2017-10-01

The Nordic Optical Telescope (NOT) Unbiased Transient Survey (NUTS; ATel #8992) reports the spectroscopic classification of ASASSN-17nb in MCG+06-17-007 and CSS170922:172546+342249 in an unknown host galaxy.

Losing the rose tinted glasses: neural substrates of unbiased belief updating in depression

PubMed Central

Garrett, Neil; Sharot, Tali; Faulkner, Paul; Korn, Christoph W.; Roiser, Jonathan P.; Dolan, Raymond J.

2014-01-01

Recent evidence suggests that a state of good mental health is associated with biased processing of information that supports a positively skewed view of the future. Depression, on the other hand, is associated with unbiased processing of such information. Here, we use brain imaging in conjunction with a belief update task administered to clinically depressed patients and healthy controls to characterize brain activity that supports unbiased belief updating in clinically depressed individuals. Our results reveal that unbiased belief updating in depression is mediated by strong neural coding of estimation errors in response to both good news (in left inferior frontal gyrus and bilateral superior frontal gyrus) and bad news (in right inferior parietal lobule and right inferior frontal gyrus) regarding the future. In contrast, intact mental health was linked to a relatively attenuated neural coding of bad news about the future. These findings identify a neural substrate mediating the breakdown of biased updating in major depression disorder, which may be essential for mental health. PMID:25221492

Allowable SEM noise for unbiased LER measurement

NASA Astrophysics Data System (ADS)

Papavieros, George; Constantoudis, Vassilios; Gogolides, Evangelos

2018-03-01

Recently, a novel method for the calculation of unbiased Line Edge Roughness based on Power Spectral Density analysis has been proposed. In this paper first an alternative method is discussed and investigated, utilizing the Height-Height Correlation Function (HHCF) of edges. The HHCF-based method enables the unbiased determination of the whole triplet of LER parameters including besides rms the correlation length and roughness exponent. The key of both methods is the sensitivity of PSD and HHCF on noise at high frequencies and short distance respectively. Secondly, we elaborate a testbed of synthesized SEM images with controlled LER and noise to justify the effectiveness of the proposed unbiased methods. Our main objective is to find out the boundaries of the method in respect to noise levels and roughness characteristics, for which the method remains reliable, i.e the maximum amount of noise allowed, for which the output results cope with the controllable known inputs. At the same time, we will also set the extremes of roughness parameters for which the methods hold their accuracy.

Tomographic quantum cryptography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liang, Yeong Cherng; Kaszlikowski, Dagomir; Englert, Berthold-Georg

2003-08-01

We present a protocol for quantum cryptography in which the data obtained for mismatched bases are used in full for the purpose of quantum state tomography. Eavesdropping on the quantum channel is seriously impeded by requiring that the outcome of the tomography is consistent with unbiased noise in the channel. We study the incoherent eavesdropping attacks that are still permissible and establish under which conditions a secure cryptographic key can be generated. The whole analysis is carried out for channels that transmit quantum systems of any finite dimension.

Fast genomic predictions via Bayesian G-BLUP and multilocus models of threshold traits including censored Gaussian data.

PubMed

Kärkkäinen, Hanni P; Sillanpää, Mikko J

2013-09-04

Because of the increased availability of genome-wide sets of molecular markers along with reduced cost of genotyping large samples of individuals, genomic estimated breeding values have become an essential resource in plant and animal breeding. Bayesian methods for breeding value estimation have proven to be accurate and efficient; however, the ever-increasing data sets are placing heavy demands on the parameter estimation algorithms. Although a commendable number of fast estimation algorithms are available for Bayesian models of continuous Gaussian traits, there is a shortage for corresponding models of discrete or censored phenotypes. In this work, we consider a threshold approach of binary, ordinal, and censored Gaussian observations for Bayesian multilocus association models and Bayesian genomic best linear unbiased prediction and present a high-speed generalized expectation maximization algorithm for parameter estimation under these models. We demonstrate our method with simulated and real data. Our example analyses suggest that the use of the extra information present in an ordered categorical or censored Gaussian data set, instead of dichotomizing the data into case-control observations, increases the accuracy of genomic breeding values predicted by Bayesian multilocus association models or by Bayesian genomic best linear unbiased prediction. Furthermore, the example analyses indicate that the correct threshold model is more accurate than the directly used Gaussian model with a censored Gaussian data, while with a binary or an ordinal data the superiority of the threshold model could not be confirmed.

Fast Genomic Predictions via Bayesian G-BLUP and Multilocus Models of Threshold Traits Including Censored Gaussian Data

PubMed Central

Kärkkäinen, Hanni P.; Sillanpää, Mikko J.

2013-01-01

Because of the increased availability of genome-wide sets of molecular markers along with reduced cost of genotyping large samples of individuals, genomic estimated breeding values have become an essential resource in plant and animal breeding. Bayesian methods for breeding value estimation have proven to be accurate and efficient; however, the ever-increasing data sets are placing heavy demands on the parameter estimation algorithms. Although a commendable number of fast estimation algorithms are available for Bayesian models of continuous Gaussian traits, there is a shortage for corresponding models of discrete or censored phenotypes. In this work, we consider a threshold approach of binary, ordinal, and censored Gaussian observations for Bayesian multilocus association models and Bayesian genomic best linear unbiased prediction and present a high-speed generalized expectation maximization algorithm for parameter estimation under these models. We demonstrate our method with simulated and real data. Our example analyses suggest that the use of the extra information present in an ordered categorical or censored Gaussian data set, instead of dichotomizing the data into case-control observations, increases the accuracy of genomic breeding values predicted by Bayesian multilocus association models or by Bayesian genomic best linear unbiased prediction. Furthermore, the example analyses indicate that the correct threshold model is more accurate than the directly used Gaussian model with a censored Gaussian data, while with a binary or an ordinal data the superiority of the threshold model could not be confirmed. PMID:23821618

Unbiased total electron content (UTEC), their fluctuations, and correlation with seismic activity over Japan

NASA Astrophysics Data System (ADS)

Cornely, Pierre-Richard; Hughes, John

2018-02-01

Earthquakes are among the most dangerous events that occur on earth and many scientists have been investigating the underlying processes that take place before earthquakes occur. These investigations are fueling efforts towards developing both single and multiple parameter earthquake forecasting methods based on earthquake precursors. One potential earthquake precursor parameter that has received significant attention within the last few years is the ionospheric total electron content (TEC). Despite its growing popularity as an earthquake precursor, TEC has been under great scrutiny because of the underlying biases associated with the process of acquiring and processing TEC data. Future work in the field will need to demonstrate our ability to acquire TEC data with the least amount of biases possible thereby preserving the integrity of the data. This paper describes a process for removing biases using raw TEC data from the standard Rinex files obtained from any global positioning satellites system. The process is based on developing an unbiased TEC (UTEC) data and model that can be more adaptable to serving as a precursor signal for earthquake forecasting. The model was used during the days and hours leading to the earthquake off the coast of Tohoku, Japan on March 11, 2011 with interesting results. The model takes advantage of the large amount of data available from the GPS Earth Observation Network of Japan to display near real-time UTEC data as the earthquake approaches and for a period of time after the earthquake occurred.

Block-circulant matrices with circulant blocks, Weil sums, and mutually unbiased bases. II. The prime power case

DOE Office of Scientific and Technical Information (OSTI.GOV)

Combescure, Monique

2009-03-15

In our previous paper [Combescure, M., 'Circulant matrices, Gauss sums and the mutually unbiased bases. I. The prime number case', Cubo A Mathematical Journal (unpublished)] we have shown that the theory of circulant matrices allows to recover the result that there exists p+1 mutually unbiased bases in dimension p, p being an arbitrary prime number. Two orthonormal bases B, B{sup '} of C{sup d} are said mutually unbiased if for all b(set-membership sign)B, for all b{sup '}(set-membership sign)B{sup '} one has that |b{center_dot}b{sup '}|=1/{radical}(d) (b{center_dot}b{sup '} Hermitian scalar product in C{sup d}). In this paper we show that the theorymore » of block-circulant matrices with circulant blocks allows to show very simply the known result that if d=p{sup n} (p a prime number and n any integer) there exists d+1 mutually unbiased bases in C{sup d}. Our result relies heavily on an idea of Klimov et al. [''Geometrical approach to the discrete Wigner function,'' J. Phys. A 39, 14471 (2006)]. As a subproduct we recover properties of quadratic Weil sums for p{>=}3, which generalizes the fact that in the prime case the quadratic Gauss sum properties follow from our results.« less

Examinations of tRNA Range of Motion Using Simulations of Cryo-EM Microscopy and X-Ray Data

PubMed Central

Caulfield, Thomas R.; Devkota, Batsal; Rollins, Geoffrey C.

2011-01-01

We examined tRNA flexibility using a combination of steered and unbiased molecular dynamics simulations. Using Maxwell's demon algorithm, molecular dynamics was used to steer X-ray structure data toward that from an alternative state obtained from cryogenic-electron microscopy density maps. Thus, we were able to fit X-ray structures of tRNA onto cryogenic-electron microscopy density maps for hybrid states of tRNA. Additionally, we employed both Maxwell's demon molecular dynamics simulations and unbiased simulation methods to identify possible ribosome-tRNA contact areas where the ribosome may discriminate tRNAs during translation. Herein, we collected >500 ns of simulation data to assess the global range of motion for tRNAs. Biased simulations can be used to steer between known conformational stop points, while unbiased simulations allow for a general testing of conformational space previously unexplored. The unbiased molecular dynamics data describes the global conformational changes of tRNA on a sub-microsecond time scale for comparison with steered data. Additionally, the unbiased molecular dynamics data was used to identify putative contacts between tRNA and the ribosome during the accommodation step of translation. We found that the primary contact regions were H71 and H92 of the 50S subunit and ribosomal proteins L14 and L16. PMID:21716650

Unbiased Estimates of Variance Components with Bootstrap Procedures

ERIC Educational Resources Information Center

Brennan, Robert L.

2007-01-01

This article provides general procedures for obtaining unbiased estimates of variance components for any random-model balanced design under any bootstrap sampling plan, with the focus on designs of the type typically used in generalizability theory. The results reported here are particularly helpful when the bootstrap is used to estimate standard…

Spectroscopic observation of Gaia17dht and Gaia17diu by NUTS (NOT Un-biased Transient Survey)

NASA Astrophysics Data System (ADS)

Fraser, M.; Dyrbye, S.; Cappella, E.

2017-12-01

The Nordic Optical Telescope (NOT) Unbiased Transient Survey (NUTS; ATel #8992) reports the spectroscopic classification of Gaia17dht/SN2017izz and Gaia17diu/SN2017jdb (in host galaxies SDSS J145121.24+283521.6 and LEDA 2753585 respectively).

Statistics as Unbiased Estimators: Exploring the Teaching of Standard Deviation

ERIC Educational Resources Information Center

Wasserman, Nicholas H.; Casey, Stephanie; Champion, Joe; Huey, Maryann

2017-01-01

This manuscript presents findings from a study about the knowledge for and planned teaching of standard deviation. We investigate how understanding variance as an unbiased (inferential) estimator--not just a descriptive statistic for the variation (spread) in data--is related to teachers' instruction regarding standard deviation, particularly…

Generalized approach for using unbiased symmetric metrics with negative values: normalized mean bias factor and normalized mean absolute error factor

EPA Science Inventory

Unbiased symmetric metrics provide a useful measure to quickly compare two datasets, with similar interpretations for both under and overestimations. Two examples include the normalized mean bias factor and normalized mean absolute error factor. However, the original formulations...

Using Imaging Methods to Interrogate Radiation-Induced Cell Signaling

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shankaran, Harish; Weber, Thomas J.; Freiin von Neubeck, Claere H.

2012-04-01

There is increasing emphasis on the use of systems biology approaches to define radiation induced responses in cells and tissues. Such approaches frequently rely on global screening using various high throughput 'omics' platforms. Although these methods are ideal for obtaining an unbiased overview of cellular responses, they often cannot reflect the inherent heterogeneity of the system or provide detailed spatial information. Additionally, performing such studies with multiple sampling time points can be prohibitively expensive. Imaging provides a complementary method with high spatial and temporal resolution capable of following the dynamics of signaling processes. In this review, we utilize specific examplesmore » to illustrate how imaging approaches have furthered our understanding of radiation induced cellular signaling. Particular emphasis is placed on protein co-localization, and oscillatory and transient signaling dynamics.« less

Describing the silent human virome with an emphasis on giant viruses.

PubMed

Popgeorgiev, Nikolay; Temmam, Sarah; Raoult, Didier; Desnues, Christelle

2013-01-01

Viruses are the most abundant obligate intracellular entities in our body. Until recently, they were only considered to be pathogens that caused a broad array of pathologies, ranging from mild disease to deaths in the most severe cases. However, recent advances in unbiased mass sequencing techniques as well as increasing epidemiological evidence have indicated that the human body is home to diverse viral species under non-pathological conditions. Despite these studies, the description of the presumably healthy viral flora, i.e. the normal human virome, is still in its infancy regarding viral composition and dynamics. This review summarizes our current knowledge of the human virome under non-pathological conditions.

Mutually unbiased bases in six dimensions: The four most distant bases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Raynal, Philippe; Lue Xin; Englert, Berthold-Georg

2011-06-15

We consider the average distance between four bases in six dimensions. The distance between two orthonormal bases vanishes when the bases are the same, and the distance reaches its maximal value of unity when the bases are unbiased. We perform a numerical search for the maximum average distance and find it to be strictly smaller than unity. This is strong evidence that no four mutually unbiased bases exist in six dimensions. We also provide a two-parameter family of three bases which, together with the canonical basis, reach the numerically found maximum of the average distance, and we conduct a detailedmore » study of the structure of the extremal set of bases.« less

Extreme Mean and Its Applications

NASA Technical Reports Server (NTRS)

Swaroop, R.; Brownlow, J. D.

1979-01-01

Extreme value statistics obtained from normally distributed data are considered. An extreme mean is defined as the mean of p-th probability truncated normal distribution. An unbiased estimate of this extreme mean and its large sample distribution are derived. The distribution of this estimate even for very large samples is found to be nonnormal. Further, as the sample size increases, the variance of the unbiased estimate converges to the Cramer-Rao lower bound. The computer program used to obtain the density and distribution functions of the standardized unbiased estimate, and the confidence intervals of the extreme mean for any data are included for ready application. An example is included to demonstrate the usefulness of extreme mean application.

Estimating Unbiased Treatment Effects in Education Using a Regression Discontinuity Design

ERIC Educational Resources Information Center

Smith, William C.

2014-01-01

The ability of regression discontinuity (RD) designs to provide an unbiased treatment effect while overcoming the ethical concerns plagued by Random Control Trials (RCTs) make it a valuable and useful approach in education evaluation. RD is the only explicitly recognized quasi-experimental approach identified by the Institute of Education…

Spectroscopic observations of ATLAS17lcs (SN 2017guv) and ASASSN-17mq (AT 2017gvo) by NUTS (NOT Un-biased Transient Survey)

NASA Astrophysics Data System (ADS)

Dong, Subo; Bose, Subhash; Stritzinger, M.; Holmbo, S.; Fraser, M.; Fedorets, G.

2017-10-01

The Nordic Optical Telescope (NOT) Unbiased Transient Survey (NUTS; ATel #8992) reports the spectroscopic classification of ATLAS17lcs (SN 2017guv) and ASASSN-17mq (AT 2017gvo) in host galaxies 2MASX J19132225-1648031 and CGCG 225-050, respectively.

Spectroscopic observations of ASASSN-17io and ATLAS17hpt (SN 2017faf) by NUTS (NOT Un-biased Transient Survey)

NASA Astrophysics Data System (ADS)

Pastorello, Andrea; Benetti, Stefano; Cappellaro, Enrico; Terreran, Giacomo; Tomasella, Lina; Fedorets, Grigori; NUTS Collaboration

2017-07-01

The Nordic Optical Telescope (NOT) Unbiased Transient Survey (NUTS; ATel #8992) reports the spectroscopic classification of ASASSN-17io in the galaxy CGCG 316-010, along with the re classification of ATLAS17hpt (SN 2017faf), which was previously classified as a SLSN-I (ATel #10549).

Contextual classification of multispectral image data: An unbiased estimator for the context distribution

NASA Technical Reports Server (NTRS)

Tilton, J. C.; Swain, P. H. (Principal Investigator); Vardeman, S. B.

1981-01-01

A key input to a statistical classification algorithm, which exploits the tendency of certain ground cover classes to occur more frequently in some spatial context than in others, is a statistical characterization of the context: the context distribution. An unbiased estimator of the context distribution is discussed which, besides having the advantage of statistical unbiasedness, has the additional advantage over other estimation techniques of being amenable to an adaptive implementation in which the context distribution estimate varies according to local contextual information. Results from applying the unbiased estimator to the contextual classification of three real LANDSAT data sets are presented and contrasted with results from non-contextual classifications and from contextual classifications utilizing other context distribution estimation techniques.

Estimation of the simple correlation coefficient.

PubMed

Shieh, Gwowen

2010-11-01

This article investigates some unfamiliar properties of the Pearson product-moment correlation coefficient for the estimation of simple correlation coefficient. Although Pearson's r is biased, except for limited situations, and the minimum variance unbiased estimator has been proposed in the literature, researchers routinely employ the sample correlation coefficient in their practical applications, because of its simplicity and popularity. In order to support such practice, this study examines the mean squared errors of r and several prominent formulas. The results reveal specific situations in which the sample correlation coefficient performs better than the unbiased and nearly unbiased estimators, facilitating recommendation of r as an effect size index for the strength of linear association between two variables. In addition, related issues of estimating the squared simple correlation coefficient are also considered.

Optimization of oligonucleotide arrays and RNA amplification protocols for analysis of transcript structure and alternative splicing.

PubMed

Castle, John; Garrett-Engele, Phil; Armour, Christopher D; Duenwald, Sven J; Loerch, Patrick M; Meyer, Michael R; Schadt, Eric E; Stoughton, Roland; Parrish, Mark L; Shoemaker, Daniel D; Johnson, Jason M

2003-01-01

Microarrays offer a high-resolution means for monitoring pre-mRNA splicing on a genomic scale. We have developed a novel, unbiased amplification protocol that permits labeling of entire transcripts. Also, hybridization conditions, probe characteristics, and analysis algorithms were optimized for detection of exons, exon-intron edges, and exon junctions. These optimized protocols can be used to detect small variations and isoform mixtures, map the tissue specificity of known human alternative isoforms, and provide a robust, scalable platform for high-throughput discovery of alternative splicing.

Optimization of oligonucleotide arrays and RNA amplification protocols for analysis of transcript structure and alternative splicing

PubMed Central

Castle, John; Garrett-Engele, Phil; Armour, Christopher D; Duenwald, Sven J; Loerch, Patrick M; Meyer, Michael R; Schadt, Eric E; Stoughton, Roland; Parrish, Mark L; Shoemaker, Daniel D; Johnson, Jason M

2003-01-01

Microarrays offer a high-resolution means for monitoring pre-mRNA splicing on a genomic scale. We have developed a novel, unbiased amplification protocol that permits labeling of entire transcripts. Also, hybridization conditions, probe characteristics, and analysis algorithms were optimized for detection of exons, exon-intron edges, and exon junctions. These optimized protocols can be used to detect small variations and isoform mixtures, map the tissue specificity of known human alternative isoforms, and provide a robust, scalable platform for high-throughput discovery of alternative splicing. PMID:14519201

Cannabinoid transmission in the prelimbic cortex bidirectionally controls opiate reward and aversion signaling through dissociable kappa versus μ-opiate receptor dependent mechanisms.

PubMed

Ahmad, Tasha; Lauzon, Nicole M; de Jaeger, Xavier; Laviolette, Steven R

2013-09-25

Cannabinoid, dopamine (DA), and opiate receptor pathways play integrative roles in emotional learning, associative memory, and sensory perception. Modulation of cannabinoid CB1 receptor transmission within the medial prefrontal cortex (mPFC) regulates the emotional valence of both rewarding and aversive experiences. Furthermore, CB1 receptor substrates functionally interact with opiate-related motivational processing circuits, particularly in the context of reward-related learning and memory. Considerable evidence demonstrates functional interactions between CB1 and DA signaling pathways during the processing of motivationally salient information. However, the role of mPFC CB1 receptor transmission in the modulation of behavioral opiate-reward processing is not currently known. Using an unbiased conditioned place preference paradigm with rats, we examined the role of intra-mPFC CB1 transmission during opiate reward learning. We report that activation or inhibition of CB1 transmission within the prelimbic cortical (PLC) division of the mPFC bidirectionally regulates the motivational valence of opiates; whereas CB1 activation switched morphine reward signaling into an aversive stimulus, blockade of CB1 transmission potentiated the rewarding properties of normally sub-reward threshold conditioning doses of morphine. Both of these effects were dependent upon DA transmission as systemic blockade of DAergic transmission prevented CB1-dependent modulation of morphine reward and aversion behaviors. We further report that CB1-mediated intra-PLC opiate motivational signaling is mediated through a μ-opiate receptor-dependent reward pathway, or a κ-opiate receptor-dependent aversion pathway, directly within the ventral tegmental area. Our results provide evidence for a novel CB1-mediated motivational valence switching mechanism within the PLC, controlling dissociable subcortical reward and aversion pathways.

Identification of a dopamine receptor-mediated opiate reward memory switch in the basolateral amygdala-nucleus accumbens circuit.

PubMed

Lintas, Alessandra; Chi, Ning; Lauzon, Nicole M; Bishop, Stephanie F; Gholizadeh, Shervin; Sun, Ninglei; Tan, Huibing; Laviolette, Steven R

2011-08-03

The basolateral amygdala (BLA), ventral tegmental area (VTA), and nucleus accumbens (NAc) play central roles in the processing of opiate-related associative reward learning and memory. The BLA receives innervation from dopaminergic fibers originating in the VTA, and both dopamine (DA) D1 and D2 receptors are expressed in this region. Using a combination of in vivo single-unit extracellular recording in the NAc combined with behavioral pharmacology studies, we have identified a double dissociation in the functional roles of DA D1 versus D2 receptor transmission in the BLA, which depends on opiate exposure state; thus, in previously opiate-naive rats, blockade of intra-BLA D1, but not D2, receptor transmission blocked the acquisition of associative opiate reward memory, measured in an unbiased conditioned place preference procedure. In direct contrast, in rats made opiate dependent and conditioned in a state of withdrawal, intra-BLA D2, but not D1, receptor blockade blocked opiate reward encoding. This functional switch was dependent on cAMP signaling as comodulation of intra-BLA cAMP levels reversed or replicated the functional effects of intra-BLA D1 or D2 transmission during opiate reward processing. Single-unit in vivo extracellular recordings performed in neurons of the NAc confirmed an opiate-state-dependent role for BLA D1/D2 transmission in NAc neuronal response patterns to morphine. Our results characterize and identify a novel opiate addiction switching mechanism directly in the BLA that can control the processing of opiate reward information as a direct function of opiate exposure state via D1 or D2 receptor signaling substrates.

Maximal Unbiased Benchmarking Data Sets for Human Chemokine Receptors and Comparative Analysis.

PubMed

Xia, Jie; Reid, Terry-Elinor; Wu, Song; Zhang, Liangren; Wang, Xiang Simon

2018-05-29

Chemokine receptors (CRs) have long been druggable targets for the treatment of inflammatory diseases and HIV-1 infection. As a powerful technique, virtual screening (VS) has been widely applied to identifying small molecule leads for modern drug targets including CRs. For rational selection of a wide variety of VS approaches, ligand enrichment assessment based on a benchmarking data set has become an indispensable practice. However, the lack of versatile benchmarking sets for the whole CRs family that are able to unbiasedly evaluate every single approach including both structure- and ligand-based VS somewhat hinders modern drug discovery efforts. To address this issue, we constructed Maximal Unbiased Benchmarking Data sets for human Chemokine Receptors (MUBD-hCRs) using our recently developed tools of MUBD-DecoyMaker. The MUBD-hCRs encompasses 13 subtypes out of 20 chemokine receptors, composed of 404 ligands and 15756 decoys so far and is readily expandable in the future. It had been thoroughly validated that MUBD-hCRs ligands are chemically diverse while its decoys are maximal unbiased in terms of "artificial enrichment", "analogue bias". In addition, we studied the performance of MUBD-hCRs, in particular CXCR4 and CCR5 data sets, in ligand enrichment assessments of both structure- and ligand-based VS approaches in comparison with other benchmarking data sets available in the public domain and demonstrated that MUBD-hCRs is very capable of designating the optimal VS approach. MUBD-hCRs is a unique and maximal unbiased benchmarking set that covers major CRs subtypes so far.

Oxyfunctionalization of the Remote C-H Bonds of Aliphatic Amines by Decatungstate Photocatalysis.

PubMed

Schultz, Danielle M; Lévesque, François; DiRocco, Daniel A; Reibarkh, Mikhail; Ji, Yining; Joyce, Leo A; Dropinski, James F; Sheng, Huaming; Sherry, Benjamin D; Davies, Ian W

2017-11-27

Aliphatic amines, oxygenated at remote positions within the molecule, represent an important class of synthetic building blocks to which there are currently no direct means of access. Reported herein is an efficient and scalable solution that relies upon decatungstate photocatalysis under acidic conditions using either H 2 O 2 or O 2 as the terminal oxidant. By using these reaction conditions a series of simple and unbiased aliphatic amine starting materials can be oxidized to value-added ketone products. Lastly, NMR spectroscopy using in situ LED-irradiated samples was utilized to monitor the kinetics of the reaction, thus enabling direct translation of the reaction into flow. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Critical point relascope sampling for unbiased volume estimation of downed coarse woody debris

Treesearch

Jeffrey H. Gove; Michael S. Williams; Mark J. Ducey; Mark J. Ducey

2005-01-01

Critical point relascope sampling is developed and shown to be design-unbiased for the estimation of log volume when used with point relascope sampling for downed coarse woody debris. The method is closely related to critical height sampling for standing trees when trees are first sampled with a wedge prism. Three alternative protocols for determining the critical...

Retransformation bias in a stem profile model

Treesearch

Raymond L. Czaplewski; David Bruce

1990-01-01

An unbiased profile model, fit to diameter divided by diameter at breast height, overestimated volume of 5.3-m log sections by 0.5 to 3.5%. Another unbiased profile model, fit to squared diameter divided by squared diameter at breast height, underestimated bole diameters by 0.2 to 2.1%. These biases are caused by retransformation of the predicted dependent variable;...

Unbiased nonorthogonal bases for tomographic reconstruction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sainz, Isabel; Klimov, Andrei B.; Roa, Luis

2010-05-15

We have developed a general method for constructing a set of nonorthogonal bases with equal separations between all different basis states in prime dimensions. The results are that the corresponding biorthogonal counterparts are pairwise unbiased with the components of the original bases. Using these bases, we derive an explicit expression for the optimal tomography in nonorthogonal bases. A special two-dimensional case is analyzed separately.

Simultaneous unbiased estimates of multiple downed wood attributes in perpendicular distance sampling

Treesearch

Mark J. Ducey; Jeffrey H. Gove; Harry T. Valentine

2008-01-01

Perpendicular distance sampling (PDS) is a fast probability-proportional-to-size method for inventory of downed wood. However, previous development of PDS had limited the method to estimating only one variable (such as volume per hectare, or surface area per hectare) at a time. Here, we develop a general design-unbiased estimator for PDS. We then show how that...

The dependability of medical students' performance ratings as documented on in-training evaluations.

PubMed

van Barneveld, Christina

2005-03-01

To demonstrate an approach to obtain an unbiased estimate of the dependability of students' performance ratings during training, when the data-collection design includes nesting of student in rater, unbalanced nest sizes, and dependent observations. In 2003, two variance components analyses of in-training evaluation (ITE) report data were conducted using urGENOVA software. In the first analysis, the dependability for the nested and unbalanced data-collection design was calculated. In the second analysis, an approach using multiple generalizability studies was used to obtain an unbiased estimate of the student variance component, resulting in an unbiased estimate of dependability. Results suggested that there is bias in estimates of the dependability of students' performance on ITEs that are attributable to the data-collection design. When the bias was corrected, the results indicated that the dependability of ratings of student performance was almost zero. The combination of the multiple generalizability studies method and the use of specialized software provides an unbiased estimate of the dependability of ratings of student performance on ITE scores for data-collection designs that include nesting of student in rater, unbalanced nest sizes, and dependent observations.

Self-balanced real-time photonic scheme for ultrafast random number generation

NASA Astrophysics Data System (ADS)

Li, Pu; Guo, Ya; Guo, Yanqiang; Fan, Yuanlong; Guo, Xiaomin; Liu, Xianglian; Shore, K. Alan; Dubrova, Elena; Xu, Bingjie; Wang, Yuncai; Wang, Anbang

2018-06-01

We propose a real-time self-balanced photonic method for extracting ultrafast random numbers from broadband randomness sources. In place of electronic analog-to-digital converters (ADCs), the balanced photo-detection technology is used to directly quantize optically sampled chaotic pulses into a continuous random number stream. Benefitting from ultrafast photo-detection, our method can efficiently eliminate the generation rate bottleneck from electronic ADCs which are required in nearly all the available fast physical random number generators. A proof-of-principle experiment demonstrates that using our approach 10 Gb/s real-time and statistically unbiased random numbers are successfully extracted from a bandwidth-enhanced chaotic source. The generation rate achieved experimentally here is being limited by the bandwidth of the chaotic source. The method described has the potential to attain a real-time rate of 100 Gb/s.

Reply to ''Comment on 'Mutually unbiased bases, orthogonal Latin squares, and hidden-variable models'''

DOE Office of Scientific and Technical Information (OSTI.GOV)

Paterek, Tomasz; Dakic, Borivoje; Brukner, Caslav

In this Reply to the preceding Comment by Hall and Rao [Phys. Rev. A 83, 036101 (2011)], we motivate terminology of our original paper and point out that further research is needed in order to (dis)prove the claimed link between every orthogonal Latin square of order being a power of a prime and a mutually unbiased basis.

Generation and evaluation of an ultra-high-field atlas with applications in DBS planning

NASA Astrophysics Data System (ADS)

Wang, Brian T.; Poirier, Stefan; Guo, Ting; Parrent, Andrew G.; Peters, Terry M.; Khan, Ali R.

2016-03-01

Purpose Deep brain stimulation (DBS) is a common treatment for Parkinson's disease (PD) and involves the use of brain atlases or intrinsic landmarks to estimate the location of target deep brain structures, such as the subthalamic nucleus (STN) and the globus pallidus pars interna (GPi). However, these structures can be difficult to localize with conventional clinical magnetic resonance imaging (MRI), and thus targeting can be prone to error. Ultra-high-field imaging at 7T has the ability to clearly resolve these structures and thus atlases built with these data have the potential to improve targeting accuracy. Methods T1 and T2-weighted images of 12 healthy control subjects were acquired using a 7T MR scanner. These images were then used with groupwise registration to generate an unbiased average template with T1w and T2w contrast. Deep brain structures were manually labelled in each subject by two raters and rater reliability was assessed. We compared the use of this unbiased atlas with two other methods of atlas-based segmentation (single-template and multi-template) for subthalamic nucleus (STN) segmentation on 7T MRI data. We also applied this atlas to clinical DBS data acquired at 1.5T to evaluate its efficacy for DBS target localization as compared to using a standard atlas. Results The unbiased templates provide superb detail of subcortical structures. Through one-way ANOVA tests, the unbiased template is significantly (p <0.05) more accurate than a single-template in atlas-based segmentation and DBS target localization tasks. Conclusion The generated unbiased averaged templates provide better visualization of deep brain nuclei and an increase in accuracy over single-template and lower field strength atlases.

Extending unbiased stereology of brain ultrastructure to three-dimensional volumes

NASA Technical Reports Server (NTRS)

Fiala, J. C.; Harris, K. M.; Koslow, S. H. (Principal Investigator)

2001-01-01

OBJECTIVE: Analysis of brain ultrastructure is needed to reveal how neurons communicate with one another via synapses and how disease processes alter this communication. In the past, such analyses have usually been based on single or paired sections obtained by electron microscopy. Reconstruction from multiple serial sections provides a much needed, richer representation of the three-dimensional organization of the brain. This paper introduces a new reconstruction system and new methods for analyzing in three dimensions the location and ultrastructure of neuronal components, such as synapses, which are distributed non-randomly throughout the brain. DESIGN AND MEASUREMENTS: Volumes are reconstructed by defining transformations that align the entire area of adjacent sections. Whole-field alignment requires rotation, translation, skew, scaling, and second-order nonlinear deformations. Such transformations are implemented by a linear combination of bivariate polynomials. Computer software for generating transformations based on user input is described. Stereological techniques for assessing structural distributions in reconstructed volumes are the unbiased bricking, disector, unbiased ratio, and per-length counting techniques. A new general method, the fractional counter, is also described. This unbiased technique relies on the counting of fractions of objects contained in a test volume. A volume of brain tissue from stratum radiatum of hippocampal area CA1 is reconstructed and analyzed for synaptic density to demonstrate and compare the techniques. RESULTS AND CONCLUSIONS: Reconstruction makes practicable volume-oriented analysis of ultrastructure using such techniques as the unbiased bricking and fractional counter methods. These analysis methods are less sensitive to the section-to-section variations in counts and section thickness, factors that contribute to the inaccuracy of other stereological methods. In addition, volume reconstruction facilitates visualization and modeling of structures and analysis of three-dimensional relationships such as synaptic connectivity.

Current and efficiency of Brownian particles under oscillating forces in entropic barriers

NASA Astrophysics Data System (ADS)

Nutku, Ferhat; Aydιner, Ekrem

2015-04-01

In this study, considering the temporarily unbiased force and different forms of oscillating forces, we investigate the current and efficiency of Brownian particles in an entropic tube structure and present the numerically obtained results. We show that different force forms give rise to different current and efficiency profiles in different optimized parameter intervals. We find that an unbiased oscillating force and an unbiased temporal force lead to the current and efficiency, which are dependent on these parameters. We also observe that the current and efficiency caused by temporal and different oscillating forces have maximum and minimum values in different parameter intervals. We conclude that the current or efficiency can be controlled dynamically by adjusting the parameters of entropic barriers and applied force. Project supported by the Funds from Istanbul University (Grant No. 45662).

An Example of an Improvable Rao-Blackwell Improvement, Inefficient Maximum Likelihood Estimator, and Unbiased Generalized Bayes Estimator.

PubMed

Galili, Tal; Meilijson, Isaac

2016-01-02

The Rao-Blackwell theorem offers a procedure for converting a crude unbiased estimator of a parameter θ into a "better" one, in fact unique and optimal if the improvement is based on a minimal sufficient statistic that is complete. In contrast, behind every minimal sufficient statistic that is not complete, there is an improvable Rao-Blackwell improvement. This is illustrated via a simple example based on the uniform distribution, in which a rather natural Rao-Blackwell improvement is uniformly improvable. Furthermore, in this example the maximum likelihood estimator is inefficient, and an unbiased generalized Bayes estimator performs exceptionally well. Counterexamples of this sort can be useful didactic tools for explaining the true nature of a methodology and possible consequences when some of the assumptions are violated. [Received December 2014. Revised September 2015.].

Quantum key distribution for composite dimensional finite systems

NASA Astrophysics Data System (ADS)

Shalaby, Mohamed; Kamal, Yasser

2017-06-01

The application of quantum mechanics contributes to the field of cryptography with very important advantage as it offers a mechanism for detecting the eavesdropper. The pioneering work of quantum key distribution uses mutually unbiased bases (MUBs) to prepare and measure qubits (or qudits). Weak mutually unbiased bases (WMUBs) have weaker properties than MUBs properties, however, unlike MUBs, a complete set of WMUBs can be constructed for systems with composite dimensions. In this paper, we study the use of weak mutually unbiased bases (WMUBs) in quantum key distribution for composite dimensional finite systems. We prove that the security analysis of using a complete set of WMUBs to prepare and measure the quantum states in the generalized BB84 protocol, gives better results than using the maximum number of MUBs that can be constructed, when they are analyzed against the intercept and resend attack.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cullen, David A; Koestner, Roland; Kukreja, Ratan

Improved conditions for imaging and spectroscopic mapping of thin perfluorosulfonic acid (PFSA) ionomer layers in fuel cell electrodes by scanning transmission electron microscopy (STEM) have been investigated. These conditions are first identified on model systems of Nafion ionomer-coated nanostructured thin films and nanoporous Si. The optimized conditions are then applied in a quantitative study of the ionomer through-layer loading for two typical electrode catalyst coatings using electron energy loss and energy dispersive X-ray spectroscopy in the transmission electron microscope. The e-beam induced damage to the perfluorosulfonic acid (PFSA) ionomer is quantified by following the fluorine mass loss with electron exposuremore » and is then mitigated by a few orders of magnitude using cryogenic specimen cooling and a higher incident electron voltage. Multivariate statistical analysis is also applied to the analysis of spectrum images for data denoising and unbiased separation of independent components related to the catalyst, ionomer, and support.« less

Lies, Damned Lies, and Survey Self-Reports? Identity as a Cause of Measurement Bias.

PubMed

Brenner, Philip S; DeLamater, John

2016-12-01

Explanations of error in survey self-reports have focused on social desirability: that respondents answer questions about normative behavior to appear prosocial to interviewers. However, this paradigm fails to explain why bias occurs even in self-administered modes like mail and web surveys. We offer an alternative explanation rooted in identity theory that focuses on measurement directiveness as a cause of bias. After completing questions about physical exercise on a web survey, respondents completed a text message-based reporting procedure, sending updates on their major activities for five days. Random assignment was then made to one of two conditions: instructions mentioned the focus of the study, physical exercise, or not. Survey responses, text updates, and records from recreation facilities were compared. Direct measures generated bias-overreporting in survey measures and reactivity in the directive text condition-but the nondirective text condition generated unbiased measures. Findings are discussed in terms of identity.

Unbiased Estimation of Refractive State of Aberrated Eyes

PubMed Central

Martin, Jesson; Vasudevan, Balamurali; Himebaugh, Nikole; Bradley, Arthur; Thibos, Larry

2011-01-01

To identify unbiased methods for estimating the target vergence required to maximize visual acuity based on wavefront aberration measurements. Experiments were designed to minimize the impact of confounding factors that have hampered previous research. Objective wavefront refractions and subjective acuity refractions were obtained for the same monochromatic wavelength. Accommodation and pupil fluctuations were eliminated by cycloplegia. Unbiased subjective refractions that maximize visual acuity for high contrast letters were performed with a computer controlled forced choice staircase procedure, using 0.125 diopter steps of defocus. All experiments were performed for two pupil diameters (3mm and 6mm). As reported in the literature, subjective refractive error does not change appreciably when the pupil dilates. For 3 mm pupils most metrics yielded objective refractions that were about 0.1D more hyperopic than subjective acuity refractions. When pupil diameter increased to 6 mm, this bias changed in the myopic direction and the variability between metrics also increased. These inaccuracies were small compared to the precision of the measurements, which implies that most metrics provided unbiased estimates of refractive state for medium and large pupils. A variety of image quality metrics may be used to determine ocular refractive state for monochromatic (635nm) light, thereby achieving accurate results without the need for empirical correction factors. PMID:21777601

Circulating tumor cell detection: A direct comparison between negative and unbiased enrichment in lung cancer.

PubMed

Xu, Yan; Liu, Biao; Ding, Fengan; Zhou, Xiaodie; Tu, Pin; Yu, Bo; He, Yan; Huang, Peilin

2017-06-01

Circulating tumor cells (CTCs), isolated as a 'liquid biopsy', may provide important diagnostic and prognostic information. Therefore, rapid, reliable and unbiased detection of CTCs are required for routine clinical analyses. It was demonstrated that negative enrichment, an epithelial marker-independent technique for isolating CTCs, exhibits a better efficiency in the detection of CTCs compared with positive enrichment techniques that only use specific anti-epithelial cell adhesion molecules. However, negative enrichment techniques incur significant cell loss during the isolation procedure, and as it is a method that uses only one type of antibody, it is inherently biased. The detection procedure and identification of cell types also relies on skilled and experienced technicians. In the present study, the detection sensitivity of using negative enrichment and a previously described unbiased detection method was compared. The results revealed that unbiased detection methods may efficiently detect >90% of cancer cells in blood samples containing CTCs. By contrast, only 40-60% of CTCs were detected by negative enrichment. Additionally, CTCs were identified in >65% of patients with stage I/II lung cancer. This simple yet efficient approach may achieve a high level of sensitivity. It demonstrates a potential for the large-scale clinical implementation of CTC-based diagnostic and prognostic strategies.

Building unbiased estimators from non-gaussian likelihoods with application to shear estimation

DOE PAGES

Madhavacheril, Mathew S.; McDonald, Patrick; Sehgal, Neelima; ...

2015-01-15

We develop a general framework for generating estimators of a given quantity which are unbiased to a given order in the difference between the true value of the underlying quantity and the fiducial position in theory space around which we expand the likelihood. We apply this formalism to rederive the optimal quadratic estimator and show how the replacement of the second derivative matrix with the Fisher matrix is a generic way of creating an unbiased estimator (assuming choice of the fiducial model is independent of data). Next we apply the approach to estimation of shear lensing, closely following the workmore » of Bernstein and Armstrong (2014). Our first order estimator reduces to their estimator in the limit of zero shear, but it also naturally allows for the case of non-constant shear and the easy calculation of correlation functions or power spectra using standard methods. Both our first-order estimator and Bernstein and Armstrong’s estimator exhibit a bias which is quadratic in true shear. Our third-order estimator is, at least in the realm of the toy problem of Bernstein and Armstrong, unbiased to 0.1% in relative shear errors Δg/g for shears up to |g| = 0.2.« less

Building unbiased estimators from non-Gaussian likelihoods with application to shear estimation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Madhavacheril, Mathew S.; Sehgal, Neelima; McDonald, Patrick

2015-01-01

We develop a general framework for generating estimators of a given quantity which are unbiased to a given order in the difference between the true value of the underlying quantity and the fiducial position in theory space around which we expand the likelihood. We apply this formalism to rederive the optimal quadratic estimator and show how the replacement of the second derivative matrix with the Fisher matrix is a generic way of creating an unbiased estimator (assuming choice of the fiducial model is independent of data). Next we apply the approach to estimation of shear lensing, closely following the workmore » of Bernstein and Armstrong (2014). Our first order estimator reduces to their estimator in the limit of zero shear, but it also naturally allows for the case of non-constant shear and the easy calculation of correlation functions or power spectra using standard methods. Both our first-order estimator and Bernstein and Armstrong's estimator exhibit a bias which is quadratic in true shear. Our third-order estimator is, at least in the realm of the toy problem of Bernstein and Armstrong, unbiased to 0.1% in relative shear errors Δg/g for shears up to |g|=0.2.« less

Predicting longitudinal trajectories of health probabilities with random-effects multinomial logit regression.

PubMed

Liu, Xian; Engel, Charles C

2012-12-20

Researchers often encounter longitudinal health data characterized with three or more ordinal or nominal categories. Random-effects multinomial logit models are generally applied to account for potential lack of independence inherent in such clustered data. When parameter estimates are used to describe longitudinal processes, however, random effects, both between and within individuals, need to be retransformed for correctly predicting outcome probabilities. This study attempts to go beyond existing work by developing a retransformation method that derives longitudinal growth trajectories of unbiased health probabilities. We estimated variances of the predicted probabilities by using the delta method. Additionally, we transformed the covariates' regression coefficients on the multinomial logit function, not substantively meaningful, to the conditional effects on the predicted probabilities. The empirical illustration uses the longitudinal data from the Asset and Health Dynamics among the Oldest Old. Our analysis compared three sets of the predicted probabilities of three health states at six time points, obtained from, respectively, the retransformation method, the best linear unbiased prediction, and the fixed-effects approach. The results demonstrate that neglect of retransforming random errors in the random-effects multinomial logit model results in severely biased longitudinal trajectories of health probabilities as well as overestimated effects of covariates on the probabilities. Copyright © 2012 John Wiley & Sons, Ltd.

An approach to checking case-crossover analyses based on equivalence with time-series methods.

PubMed

Lu, Yun; Symons, James Morel; Geyh, Alison S; Zeger, Scott L

2008-03-01

The case-crossover design has been increasingly applied to epidemiologic investigations of acute adverse health effects associated with ambient air pollution. The correspondence of the design to that of matched case-control studies makes it inferentially appealing for epidemiologic studies. Case-crossover analyses generally use conditional logistic regression modeling. This technique is equivalent to time-series log-linear regression models when there is a common exposure across individuals, as in air pollution studies. Previous methods for obtaining unbiased estimates for case-crossover analyses have assumed that time-varying risk factors are constant within reference windows. In this paper, we rely on the connection between case-crossover and time-series methods to illustrate model-checking procedures from log-linear model diagnostics for time-stratified case-crossover analyses. Additionally, we compare the relative performance of the time-stratified case-crossover approach to time-series methods under 3 simulated scenarios representing different temporal patterns of daily mortality associated with air pollution in Chicago, Illinois, during 1995 and 1996. Whenever a model-be it time-series or case-crossover-fails to account appropriately for fluctuations in time that confound the exposure, the effect estimate will be biased. It is therefore important to perform model-checking in time-stratified case-crossover analyses rather than assume the estimator is unbiased.

Comparison of photo detectors and operating conditions for decay time determination in phosphor thermometry

NASA Astrophysics Data System (ADS)

Knappe, C.; Nada, F. Abou; Richter, M.; Aldén, M.

2012-09-01

This work compares the extent of linear response regions from standard time-resolving optical detectors for phosphor thermometry. Different types of photomultipliers (ordinary and time-gated) as well as an avalanche photodiode were tested and compared using the phosphorescence decay time of cadmium tungstate (CdWO4). Effects originating from incipient detector saturation are revealed as a change in evaluated phosphorescence decay time, which was found to be a more sensitive measure for saturation than the conventional signal strength comparison between in- and output. Since the decay time of thermographic phosphors is used for temperature determination systematic temperature errors in the order of several tens of Kelvins may be introduced. Saturation from the initial intensity is isolated from temporally developed saturation by varying the CdWO4 decay time over the microsecond to nanosecond range, resultant of varying the temperature from 290 to 580 K. A detector mapping procedure is developed in order to identify linear response regions where the decay-to-temperature evaluations are unbiased. In addition, this mapping procedure generates a library of the degree of distortion for operating points outside of linear response regions. Signals collected in the partly saturated regime can thus be corrected to their unbiased value using this library, extending the usable detector operating range significantly.

Conditionally Unbiased Bounded Influence Robust Regression with Applications to Generalized Linear Models.

DTIC Science & Technology

1987-03-01

some general results and definitions from robust statistics (see Hampel et. al.. 1986). The influence function of an M-Lstimator is IC (y.x.0) = D_...estimator is (4,T T T (\\cond(YXGB) . Yx(x,O.B) ) . where X~xO.) =x T T8 xT-lx 1/2 = x x v(x . b/(x B x) ) - B. The influence function of this...the influence function for (3.7) and (3.8) is equal to -. Eo[\\Pcond(y.X.,B)] -1 cond(Yx. ,B). (4.3) On the other hand, the influence function for the

Effects of Simulated Surface Effect Ship Motions on Crew Habitability. Phase II. Volume 1. Summary Report and Comments

DTIC Science & Technology

1981-04-01

one 24-hour exposure to that condition may be regarded as the most complete and unbiased for determining some effects of a type of simulated SES...eliminated entirely. The ability to predict in advance the resultant effects of motion exposure thus seems to depend on the existance of a given...F• 198OF1L-0/I- =•RAI. )81 -• i . _j EFFECT OF.SIMULATED 1 S URFACE EFFECT SHIP J•OTIONS_2 ON CREW HABITABILITY 1PHASE 1J_ "I ,,OLUME 1 iI SUMMARY

Resonant tunneling in graphene pseudomagnetic quantum dots.

PubMed

Qi, Zenan; Bahamon, D A; Pereira, Vitor M; Park, Harold S; Campbell, D K; Neto, A H Castro

2013-06-12

Realistic relaxed configurations of triaxially strained graphene quantum dots are obtained from unbiased atomistic mechanical simulations. The local electronic structure and quantum transport characteristics of y-junctions based on such dots are studied, revealing that the quasi-uniform pseudomagnetic field induced by strain restricts transport to Landau level- and edge state-assisted resonant tunneling. Valley degeneracy is broken in the presence of an external field, allowing the selective filtering of the valley and chirality of the states assisting in the resonant tunneling. Asymmetric strain conditions can be explored to select the exit channel of the y-junction.

Ventral tegmental area GABA neurons and opiate motivation

PubMed Central

Vargas-Perez, Hector; Mabey, Jennifer K.; Shin, Samuel I.; Steffensen, Scott C.; van der Kooy, Derek

2013-01-01

Rational Past research has demonstrated that when an animal changes from a previously drug-naive to an opiate-dependent and withdrawn state, morphine’s motivational effects are switched from a tegmental pedunculopontine nucleus (TPP)-dependent to a dopamine-dependent pathway. Interestingly, a corresponding change is observed in ventral tegmental area (VTA) GABAA receptors, which change from mediating hyperpolarization of VTA GABA neurons to mediating depolarization. Objectives The present study investigated whether pharmacological manipulation of VTA GABAA receptor activity could directly influence the mechanisms underlying opiate motivation. Results Using an unbiased place conditioning procedure, we demonstrated that in Wistar rats, intra-VTA administration of furosemide, a Cl− cotransporter inhibitor, was able to promote a switch in the mechanisms underlying morphine’s motivational properties, one which is normally observed only after chronic opiate exposure. This behavioral switch was prevented by intra-VTA administration of acetazolamide, an inhibitor of the bicarbonate ion-producing carbonic anhydrase enzyme. Electrophysiological recordings of mouse VTA showed that furosemide reduced the sensitivity of VTA GABA neurons to inhibition by the GABAA receptor agonist muscimol, instead increasing the firing rate of a significant subset of these GABA neurons. Conclusion Our results suggest that the carbonic anhydrase enzyme may constitute part of a common VTA GABA neuron-based biological pathway responsible for controlling the mechanisms underlying opiate motivation, supporting the hypothesis that VTA GABAA receptor hyperpolarization or depolarization is responsible for selecting TPP- or dopamine-dependent motivational outputs, respectively. PMID:23392354

Angular dependence models for radiance to flux conversion

NASA Technical Reports Server (NTRS)

Green, Richard N.; Suttles, John T.; Wielicki, Bruce A.

1990-01-01

Angular dependence models (ADM) used for converting the measured radiance to flux at the top of the atmosphere are reviewed, and emphasis is placed on the measure of their effectiveness and the implications of requiring the ADMs to satisfy reciprocity. The overall significance of the ADMs is figured out by analyzing the same satellite data with a single Lambertian model, single mean model, and the 12 Earth Radiation Budget Experiment (ERBE) ADMs. It is shown that the Lambertian ADM is inadequate, while the mean ADM results in nearly unbiased fluxes but creates substantial differences for individual pixel fluxes. The standard ERBE ADM works well except for a 10-pct to 15-pct albedo growth across the scan; a modified ADM based on the standard ERBE ADM but forced to satisfy the principle of reciprocity increases the limb brightening and reduces the albedo growth but does not improve the scanner and nonscanner intercomparison.

Defining the human deubiquitinating enzyme interaction landscape.

PubMed

Sowa, Mathew E; Bennett, Eric J; Gygi, Steven P; Harper, J Wade

2009-07-23

Deubiquitinating enzymes (Dubs) function to remove covalently attached ubiquitin from proteins, thereby controlling substrate activity and/or abundance. For most Dubs, their functions, targets, and regulation are poorly understood. To systematically investigate Dub function, we initiated a global proteomic analysis of Dubs and their associated protein complexes. This was accomplished through the development of a software platform called CompPASS, which uses unbiased metrics to assign confidence measurements to interactions from parallel nonreciprocal proteomic data sets. We identified 774 candidate interacting proteins associated with 75 Dubs. Using Gene Ontology, interactome topology classification, subcellular localization, and functional studies, we link Dubs to diverse processes, including protein turnover, transcription, RNA processing, DNA damage, and endoplasmic reticulum-associated degradation. This work provides the first glimpse into the Dub interaction landscape, places previously unstudied Dubs within putative biological pathways, and identifies previously unknown interactions and protein complexes involved in this increasingly important arm of the ubiquitin-proteasome pathway.

Defining the Human Deubiquitinating Enzyme Interaction Landscape

PubMed Central

Sowa, Mathew E.; Bennett, Eric J.; Gygi, Steven P.; Harper, J. Wade

2009-01-01

Summary Deubiquitinating enzymes (Dubs) function to remove covalently attached ubiquitin from proteins, thereby controlling substrate activity and/or abundance. For most Dubs, their functions, targets, and regulation are poorly understood. To systematically investigate Dub function, we initiated a global proteomic analysis of Dubs and their associated protein complexes. This was accomplished through the development of a software platform, called CompPASS, which uses unbiased metrics to assign confidence measurements to interactions from parallel non-reciprocal proteomic datasets. We identified 774 candidate interacting proteins associated with 75 Dubs. Using Gene Ontology, interactome topology classification, sub-cellular localization and functional studies, we link Dubs to diverse processes, including protein turnover, transcription, RNA processing, DNA damage, and endoplasmic reticulum-associated degradation. This work provides the first glimpse into the Dub interaction landscape, places previously unstudied Dubs within putative biological pathways, and identifies previously unknown interactions and protein complexes involved in this increasingly important arm of the ubiquitin-proteasome pathway. PMID:19615732

Systematic versus random sampling in stereological studies.

PubMed

West, Mark J

2012-12-01

The sampling that takes place at all levels of an experimental design must be random if the estimate is to be unbiased in a statistical sense. There are two fundamental ways by which one can make a random sample of the sections and positions to be probed on the sections. Using a card-sampling analogy, one can pick any card at all out of a deck of cards. This is referred to as independent random sampling because the sampling of any one card is made without reference to the position of the other cards. The other approach to obtaining a random sample would be to pick a card within a set number of cards and others at equal intervals within the deck. Systematic sampling along one axis of many biological structures is more efficient than random sampling, because most biological structures are not randomly organized. This article discusses the merits of systematic versus random sampling in stereological studies.

Motion-induced phase error estimation and correction in 3D diffusion tensor imaging.

PubMed

Van, Anh T; Hernando, Diego; Sutton, Bradley P

2011-11-01

A multishot data acquisition strategy is one way to mitigate B0 distortion and T2∗ blurring for high-resolution diffusion-weighted magnetic resonance imaging experiments. However, different object motions that take place during different shots cause phase inconsistencies in the data, leading to significant image artifacts. This work proposes a maximum likelihood estimation and k-space correction of motion-induced phase errors in 3D multishot diffusion tensor imaging. The proposed error estimation is robust, unbiased, and approaches the Cramer-Rao lower bound. For rigid body motion, the proposed correction effectively removes motion-induced phase errors regardless of the k-space trajectory used and gives comparable performance to the more computationally expensive 3D iterative nonlinear phase error correction method. The method has been extended to handle multichannel data collected using phased-array coils. Simulation and in vivo data are shown to demonstrate the performance of the method.

Quantum Spin Ice under a [111] Magnetic Field: From Pyrochlore to Kagome

NASA Astrophysics Data System (ADS)

Bojesen, Troels Arnfred; Onoda, Shigeki

2017-12-01

Quantum spin ice, modeled for magnetic rare-earth pyrochlores, has attracted great interest for hosting a U(1) quantum spin liquid, which involves spin-ice monopoles as gapped deconfined spinons, as well as gapless excitations analogous to photons. However, the global phase diagram under a [111] magnetic field remains open. Here we uncover by means of unbiased quantum Monte Carlo simulations that a supersolid of monopoles, showing both a superfluidity and a partial ionization, intervenes the kagome spin ice and a fully ionized monopole insulator, in contrast to classical spin ice where a direct discontinuous phase transition takes place. We also show that on cooling, kagome spin ice evolves towards a valence-bond solid similar to what appears in the associated kagome lattice model [S. V. Isakov et al., Phys. Rev. Lett. 97, 147202 (2006), 10.1103/PhysRevLett.97.147202]. Possible relevance to experiments is discussed.

Developing Novel Therapeutics Targeting Undifferentiated and Castration-Resistant Prostate Cancer Stem Cells

DTIC Science & Technology

2016-10-01

identify PCSC- specific homing peptides ; and 2) To perform unbiased drug library screening to identify novel PCSC-targeting chemicals. In the past...display library (PDL) screening in PSA-/lo PCa cells to identify PCSC- specific homing peptides ; and 2) To perform unbiased drug library screening to...Goals of the Project (SOW): Aim 1: To perform phage display library (PDL) screening in PSA-/lo PCa cells to identify PCSC- specific homing peptides

What Do We Know about Using Value-Added to Compare Teachers Who Work in Different Schools? What We Know Series: Value-Added Methods and Applications. Knowledge Brief 10

ERIC Educational Resources Information Center

Raudenbush, Stephen

2013-01-01

This brief considers the problem of using value-added scores to compare teachers who work in different schools. The author focuses on whether such comparisons can be regarded as fair, or, in statistical language, "unbiased." An unbiased measure does not systematically favor teachers because of the backgrounds of the students they are…

Long Term Follow up of the Delayed Effects of Acute Radiation Exposure in Primates

DTIC Science & Technology

2017-10-01

66 of 94 We will then use shRNAs and/or CRISPR constructs targeting the gene of interest to knock down its expression in stem cells prior to...DLBCLs Mutational profiling identifies 150 driver genes Gene expression identifies sub- groups including cell of origin Unbiased CRISPR screen...Exome sequencing in 1,001 DLBCL patients comprehensively identifies 150 driver genes d Unbiased CRISPR screen in DLBCL cell lines identifies essential

Four photon parametric amplification. [in unbiased Josephson junction

NASA Technical Reports Server (NTRS)

Parrish, P. T.; Feldman, M. J.; Ohta, H.; Chiao, R. Y.

1974-01-01

An analysis is presented describing four-photon parametric amplification in an unbiased Josephson junction. Central to the theory is the model of the Josephson effect as a nonlinear inductance. Linear, small signal analysis is applied to the two-fluid model of the Josephson junction. The gain, gain-bandwidth product, high frequency limit, and effective noise temperature are calculated for a cavity reflection amplifier. The analysis is extended to multiple (series-connected) junctions and subharmonic pumping.

A Simple Joint Estimation Method of Residual Frequency Offset and Sampling Frequency Offset for DVB Systems

NASA Astrophysics Data System (ADS)

Kwon, Ki-Won; Cho, Yongsoo

This letter presents a simple joint estimation method for residual frequency offset (RFO) and sampling frequency offset (STO) in OFDM-based digital video broadcasting (DVB) systems. The proposed method selects a continual pilot (CP) subset from an unsymmetrically and non-uniformly distributed CP set to obtain an unbiased estimator. Simulation results show that the proposed method using a properly selected CP subset is unbiased and performs robustly.

Seismic random noise removal by delay-compensation time-frequency peak filtering

NASA Astrophysics Data System (ADS)

Yu, Pengjun; Li, Yue; Lin, Hongbo; Wu, Ning

2017-06-01

Over the past decade, there has been an increasing awareness of time-frequency peak filtering (TFPF) due to its outstanding performance in suppressing non-stationary and strong seismic random noise. The traditional approach based on time-windowing achieves local linearity and meets the unbiased estimation. However, the traditional TFPF (including the improved algorithms with alterable window lengths) could hardly relieve the contradiction between removing noise and recovering the seismic signal, and this situation is more obvious in wave crests and troughs, even for alterable window lengths (WL). To improve the efficiency of the algorithm, the following TFPF in the time-space domain is applied, such as in the Radon domain and radial trace domain. The time-space transforms obtain a reduced-frequency input to reduce the TFPF error and stretch the desired signal along a certain direction, therefore the time-space development brings an improvement by both enhancing reflection events and attenuating noise. It still proves limited in application because the direction should be matched as a straight line or quadratic curve. As a result, waveform distortion and false seismic events may appear when processing the complex stratum record. The main emphasis in this article is placed on the time-space TFPF applicable expansion. The reconstructed signal in delay-compensation TFPF, which is generated according to the similarity among the reflection events, overcomes the limitation of the direction curve fitting. Moreover, the reconstructed signal just meets the TFPF linearity unbiased estimation and integrates signal reservation with noise attenuation. Experiments on both the synthetic model and field data indicate that delay-compensation TFPF has a better performance over the conventional filtering algorithms.

Test of mutually unbiased bases for six-dimensional photonic quantum systems

PubMed Central

D'Ambrosio, Vincenzo; Cardano, Filippo; Karimi, Ebrahim; Nagali, Eleonora; Santamato, Enrico; Marrucci, Lorenzo; Sciarrino, Fabio

2013-01-01

In quantum information, complementarity of quantum mechanical observables plays a key role. The eigenstates of two complementary observables form a pair of mutually unbiased bases (MUBs). More generally, a set of MUBs consists of bases that are all pairwise unbiased. Except for specific dimensions of the Hilbert space, the maximal sets of MUBs are unknown in general. Even for a dimension as low as six, the identification of a maximal set of MUBs remains an open problem, although there is strong numerical evidence that no more than three simultaneous MUBs do exist. Here, by exploiting a newly developed holographic technique, we implement and test different sets of three MUBs for a single photon six-dimensional quantum state (a “qusix”), encoded exploiting polarization and orbital angular momentum of photons. A close agreement is observed between theory and experiments. Our results can find applications in state tomography, quantitative wave-particle duality, quantum key distribution. PMID:24067548

Test of mutually unbiased bases for six-dimensional photonic quantum systems.

PubMed

D'Ambrosio, Vincenzo; Cardano, Filippo; Karimi, Ebrahim; Nagali, Eleonora; Santamato, Enrico; Marrucci, Lorenzo; Sciarrino, Fabio

2013-09-25

In quantum information, complementarity of quantum mechanical observables plays a key role. The eigenstates of two complementary observables form a pair of mutually unbiased bases (MUBs). More generally, a set of MUBs consists of bases that are all pairwise unbiased. Except for specific dimensions of the Hilbert space, the maximal sets of MUBs are unknown in general. Even for a dimension as low as six, the identification of a maximal set of MUBs remains an open problem, although there is strong numerical evidence that no more than three simultaneous MUBs do exist. Here, by exploiting a newly developed holographic technique, we implement and test different sets of three MUBs for a single photon six-dimensional quantum state (a "qusix"), encoded exploiting polarization and orbital angular momentum of photons. A close agreement is observed between theory and experiments. Our results can find applications in state tomography, quantitative wave-particle duality, quantum key distribution.

Graph-state formalism for mutually unbiased bases

NASA Astrophysics Data System (ADS)

Spengler, Christoph; Kraus, Barbara

2013-11-01

A pair of orthonormal bases is called mutually unbiased if all mutual overlaps between any element of one basis and an arbitrary element of the other basis coincide. In case the dimension, d, of the considered Hilbert space is a power of a prime number, complete sets of d+1 mutually unbiased bases (MUBs) exist. Here we present a method based on the graph-state formalism to construct such sets of MUBs. We show that for n p-level systems, with p being prime, one particular graph suffices to easily construct a set of pn+1 MUBs. In fact, we show that a single n-dimensional vector, which is associated with this graph, can be used to generate a complete set of MUBs and demonstrate that this vector can be easily determined. Finally, we discuss some advantages of our formalism regarding the analysis of entanglement structures in MUBs, as well as experimental realizations.

Diallel analysis for sex-linked and maternal effects.

PubMed

Zhu, J; Weir, B S

1996-01-01

Genetic models including sex-linked and maternal effects as well as autosomal gene effects are described. Monte Carlo simulations were conducted to compare efficiencies of estimation by minimum norm quadratic unbiased estimation (MINQUE) and restricted maximum likelihood (REML) methods. MINQUE(1), which has 1 for all prior values, has a similar efficiency to MINQUE(θ), which requires prior estimates of parameter values. MINQUE(1) has the advantage over REML of unbiased estimation and convenient computation. An adjusted unbiased prediction (AUP) method is developed for predicting random genetic effects. AUP is desirable for its easy computation and unbiasedness of both mean and variance of predictors. The jackknife procedure is appropriate for estimating the sampling variances of estimated variances (or covariances) and of predicted genetic effects. A t-test based on jackknife variances is applicable for detecting significance of variation. Worked examples from mice and silkworm data are given in order to demonstrate variance and covariance estimation and genetic effect prediction.

Mutually unbiased coarse-grained measurements of two or more phase-space variables

NASA Astrophysics Data System (ADS)

Paul, E. C.; Walborn, S. P.; Tasca, D. S.; Rudnicki, Łukasz

2018-05-01

Mutual unbiasedness of the eigenstates of phase-space operators—such as position and momentum, or their standard coarse-grained versions—exists only in the limiting case of infinite squeezing. In Phys. Rev. Lett. 120, 040403 (2018), 10.1103/PhysRevLett.120.040403, it was shown that mutual unbiasedness can be recovered for periodic coarse graining of these two operators. Here we investigate mutual unbiasedness of coarse-grained measurements for more than two phase-space variables. We show that mutual unbiasedness can be recovered between periodic coarse graining of any two nonparallel phase-space operators. We illustrate these results through optics experiments, using the fractional Fourier transform to prepare and measure mutually unbiased phase-space variables. The differences between two and three mutually unbiased measurements is discussed. Our results contribute to bridging the gap between continuous and discrete quantum mechanics, and they could be useful in quantum-information protocols.

Modeling Particle Exposure in US Trucking Terminals

PubMed Central

Davis, ME; Smith, TJ; Laden, F; Hart, JE; Ryan, LM; Garshick, E

2007-01-01

Multi-tiered sampling approaches are common in environmental and occupational exposure assessment, where exposures for a given individual are often modeled based on simultaneous measurements taken at multiple indoor and outdoor sites. The monitoring data from such studies is hierarchical by design, imposing a complex covariance structure that must be accounted for in order to obtain unbiased estimates of exposure. Statistical methods such as structural equation modeling (SEM) represent a useful alternative to simple linear regression in these cases, providing simultaneous and unbiased predictions of each level of exposure based on a set of covariates specific to the exposure setting. We test the SEM approach using data from a large exposure assessment of diesel and combustion particles in the US trucking industry. The exposure assessment includes data from 36 different trucking terminals across the United States sampled between 2001 and 2005, measuring PM2.5 and its elemental carbon (EC), organic carbon (OC) components, by personal monitoring, and sampling at two indoor work locations and an outdoor “background” location. Using the SEM method, we predict: 1) personal exposures as a function of work related exposure and smoking status; 2) work related exposure as a function of terminal characteristics, indoor ventilation, job location, and background exposure conditions; and 3) background exposure conditions as a function of weather, nearby source pollution, and other regional differences across terminal sites. The primary advantage of SEMs in this setting is the ability to simultaneously predict exposures at each of the sampling locations, while accounting for the complex covariance structure among the measurements and descriptive variables. The statistically significant results and high R2 values observed from the trucking industry application supports the broader use of this approach in exposure assessment modeling. PMID:16856739

Cross-Layer Resource Allocation for Wireless Visual Sensor Networks and Mobile Ad Hoc Networks

DTIC Science & Technology

2014-10-01

MMD), minimizes the maximum dis- tortion among all nodes of the network, promoting a rather unbiased treatment of the nodes. We employed the Particle...achieve the ideal tradeoff between the transmitted video quality and energy consumption. Each sensor node has a bit rate that can be used for both...Distortion (MMD), minimizes the maximum distortion among all nodes of the network, promoting a rather unbiased treatment of the nodes. For both criteria

Unbiased estimators for spatial distribution functions of classical fluids

NASA Astrophysics Data System (ADS)

Adib, Artur B.; Jarzynski, Christopher

2005-01-01

We use a statistical-mechanical identity closely related to the familiar virial theorem, to derive unbiased estimators for spatial distribution functions of classical fluids. In particular, we obtain estimators for both the fluid density ρ(r) in the vicinity of a fixed solute and the pair correlation g(r) of a homogeneous classical fluid. We illustrate the utility of our estimators with numerical examples, which reveal advantages over traditional histogram-based methods of computing such distributions.

Transient photocurrent in molecular junctions: singlet switching on and triplet blocking.

PubMed

Petrov, E G; Leonov, V O; Snitsarev, V

2013-05-14

The kinetic approach adapted to describe charge transmission in molecular junctions, is used for the analysis of the photocurrent under conditions of moderate light intensity of the photochromic molecule. In the framework of the HOMO-LUMO model for the single electron molecular states, the analytic expressions describing the temporary behavior of the transient and steady state sequential (hopping) as well as direct (tunnel) current components have been derived. The conditions at which the current components achieve their maximal values are indicated. It is shown that if the rates of charge transmission in the unbiased molecular diode are much lower than the intramolecular singlet-singlet excitation/de-excitation rate, and the threefold degenerated triplet excited state of the molecule behaves like a trap blocking the charge transmission, a possibility of a large peak-like transient switch-on photocurrent arises.

Biological Bases of Space Radiation Risk

NASA Technical Reports Server (NTRS)

1997-01-01

In this session, Session JP4, the discussion focuses on the following topics: Hematopoiesis Dynamics in Irradiated Mammals, Mathematical Modeling; Estimating Health Risks in Space from Galactic Cosmic Rays; Failure of Heavy Ions to Affect Physiological Integrity of the Corneal Endothelial Monolayer; Application of an Unbiased Two-Gel CDNA Library Screening Method to Expression Monitoring of Genes in Irradiated Versus Control Cells; Detection of Radiation-Induced DNA Strand Breaks in Mammalian Cells By Enzymatic Post-Labeling; Evaluation of Bleomycin-Induced Chromosome Aberrations Under Microgravity Conditions in Human Lymphocytes, Using "Fish" Techniques; Technical Description of the Space Exposure Biology Assembly Seba on ISS; and Cytogenetic Research in Biological Dosimetry.

Stretchy binary classification.

PubMed

Toh, Kar-Ann; Lin, Zhiping; Sun, Lei; Li, Zhengguo

2018-01-01

In this article, we introduce an analytic formulation for compressive binary classification. The formulation seeks to solve the least ℓ p -norm of the parameter vector subject to a classification error constraint. An analytic and stretchable estimation is conjectured where the estimation can be viewed as an extension of the pseudoinverse with left and right constructions. Our variance analysis indicates that the estimation based on the left pseudoinverse is unbiased and the estimation based on the right pseudoinverse is biased. Sparseness can be obtained for the biased estimation under certain mild conditions. The proposed estimation is investigated numerically using both synthetic and real-world data. Copyright © 2017 Elsevier Ltd. All rights reserved.

Noncommuting observables in quantum detection and estimation theory

NASA Technical Reports Server (NTRS)

Helstrom, C. W.

1972-01-01

Basing decisions and estimates on simultaneous approximate measurements of noncommuting observables in a quantum receiver is shown to be equivalent to measuring commuting projection operators on a larger Hilbert space than that of the receiver itself. The quantum-mechanical Cramer-Rao inequalities derived from right logarithmic derivatives and symmetrized logarithmic derivatives of the density operator are compared, and it is shown that the latter give superior lower bounds on the error variances of individual unbiased estimates of arrival time and carrier frequency of a coherent signal. For a suitably weighted sum of the error variances of simultaneous estimates of these, the former yield the superior lower bound under some conditions.

Two-stage sequential sampling: A neighborhood-free adaptive sampling procedure

USGS Publications Warehouse

Salehi, M.; Smith, D.R.

2005-01-01

Designing an efficient sampling scheme for a rare and clustered population is a challenging area of research. Adaptive cluster sampling, which has been shown to be viable for such a population, is based on sampling a neighborhood of units around a unit that meets a specified condition. However, the edge units produced by sampling neighborhoods have proven to limit the efficiency and applicability of adaptive cluster sampling. We propose a sampling design that is adaptive in the sense that the final sample depends on observed values, but it avoids the use of neighborhoods and the sampling of edge units. Unbiased estimators of population total and its variance are derived using Murthy's estimator. The modified two-stage sampling design is easy to implement and can be applied to a wider range of populations than adaptive cluster sampling. We evaluate the proposed sampling design by simulating sampling of two real biological populations and an artificial population for which the variable of interest took the value either 0 or 1 (e.g., indicating presence and absence of a rare event). We show that the proposed sampling design is more efficient than conventional sampling in nearly all cases. The approach used to derive estimators (Murthy's estimator) opens the door for unbiased estimators to be found for similar sequential sampling designs. ?? 2005 American Statistical Association and the International Biometric Society.

Absorption and folding of melittin onto lipid bilayer membranes via unbiased atomic detail microsecond molecular dynamics simulation.

PubMed

Chen, Charles H; Wiedman, Gregory; Khan, Ayesha; Ulmschneider, Martin B

2014-09-01

Unbiased molecular simulation is a powerful tool to study the atomic details driving functional structural changes or folding pathways of highly fluid systems, which present great challenges experimentally. Here we apply unbiased long-timescale molecular dynamics simulation to study the ab initio folding and partitioning of melittin, a template amphiphilic membrane active peptide. The simulations reveal that the peptide binds strongly to the lipid bilayer in an unstructured configuration. Interfacial folding results in a localized bilayer deformation. Akin to purely hydrophobic transmembrane segments the surface bound native helical conformer is highly resistant against thermal denaturation. Circular dichroism spectroscopy experiments confirm the strong binding and thermostability of the peptide. The study highlights the utility of molecular dynamics simulations for studying transient mechanisms in fluid lipid bilayer systems. This article is part of a Special Issue entitled: Interfacially Active Peptides and Proteins. Guest Editors: William C. Wimley and Kalina Hristova. Copyright © 2014. Published by Elsevier B.V.

Mixed model approaches for diallel analysis based on a bio-model.

PubMed

Zhu, J; Weir, B S

1996-12-01

A MINQUE(1) procedure, which is minimum norm quadratic unbiased estimation (MINQUE) method with 1 for all the prior values, is suggested for estimating variance and covariance components in a bio-model for diallel crosses. Unbiasedness and efficiency of estimation were compared for MINQUE(1), restricted maximum likelihood (REML) and MINQUE theta which has parameter values for the prior values. MINQUE(1) is almost as efficient as MINQUE theta for unbiased estimation of genetic variance and covariance components. The bio-model is efficient and robust for estimating variance and covariance components for maternal and paternal effects as well as for nuclear effects. A procedure of adjusted unbiased prediction (AUP) is proposed for predicting random genetic effects in the bio-model. The jack-knife procedure is suggested for estimation of sampling variances of estimated variance and covariance components and of predicted genetic effects. Worked examples are given for estimation of variance and covariance components and for prediction of genetic merits.

Uncertainty relation based on unbiased parameter estimations

NASA Astrophysics Data System (ADS)

Sun, Liang-Liang; Song, Yong-Shun; Qiao, Cong-Feng; Yu, Sixia; Chen, Zeng-Bing

2017-02-01

Heisenberg's uncertainty relation has been extensively studied in spirit of its well-known original form, in which the inaccuracy measures used exhibit some controversial properties and don't conform with quantum metrology, where the measurement precision is well defined in terms of estimation theory. In this paper, we treat the joint measurement of incompatible observables as a parameter estimation problem, i.e., estimating the parameters characterizing the statistics of the incompatible observables. Our crucial observation is that, in a sequential measurement scenario, the bias induced by the first unbiased measurement in the subsequent measurement can be eradicated by the information acquired, allowing one to extract unbiased information of the second measurement of an incompatible observable. In terms of Fisher information we propose a kind of information comparison measure and explore various types of trade-offs between the information gains and measurement precisions, which interpret the uncertainty relation as surplus variance trade-off over individual perfect measurements instead of a constraint on extracting complete information of incompatible observables.

Maximum unbiased validation (MUV) data sets for virtual screening based on PubChem bioactivity data.

PubMed

Rohrer, Sebastian G; Baumann, Knut

2009-02-01

Refined nearest neighbor analysis was recently introduced for the analysis of virtual screening benchmark data sets. It constitutes a technique from the field of spatial statistics and provides a mathematical framework for the nonparametric analysis of mapped point patterns. Here, refined nearest neighbor analysis is used to design benchmark data sets for virtual screening based on PubChem bioactivity data. A workflow is devised that purges data sets of compounds active against pharmaceutically relevant targets from unselective hits. Topological optimization using experimental design strategies monitored by refined nearest neighbor analysis functions is applied to generate corresponding data sets of actives and decoys that are unbiased with regard to analogue bias and artificial enrichment. These data sets provide a tool for Maximum Unbiased Validation (MUV) of virtual screening methods. The data sets and a software package implementing the MUV design workflow are freely available at http://www.pharmchem.tu-bs.de/lehre/baumann/MUV.html.

Computational tools for exact conditional logistic regression.

PubMed

Corcoran, C; Mehta, C; Patel, N; Senchaudhuri, P

Logistic regression analyses are often challenged by the inability of unconditional likelihood-based approximations to yield consistent, valid estimates and p-values for model parameters. This can be due to sparseness or separability in the data. Conditional logistic regression, though useful in such situations, can also be computationally unfeasible when the sample size or number of explanatory covariates is large. We review recent developments that allow efficient approximate conditional inference, including Monte Carlo sampling and saddlepoint approximations. We demonstrate through real examples that these methods enable the analysis of significantly larger and more complex data sets. We find in this investigation that for these moderately large data sets Monte Carlo seems a better alternative, as it provides unbiased estimates of the exact results and can be executed in less CPU time than can the single saddlepoint approximation. Moreover, the double saddlepoint approximation, while computationally the easiest to obtain, offers little practical advantage. It produces unreliable results and cannot be computed when a maximum likelihood solution does not exist. Copyright 2001 John Wiley & Sons, Ltd.

29 CFR 32.15 - Preemployment inquiries.

Code of Federal Regulations, 2012 CFR

2012-07-01

... recipient states clearly on any written questionnaire used for this purpose or makes clear orally, if no... was conditionally placed in a job pool or conditionally placed on an eligibility list prior to the... conditionally in a job pool or conditionally placed on an eligibility list; that is the medical results were the...

29 CFR 32.15 - Preemployment inquiries.

Code of Federal Regulations, 2013 CFR

2013-07-01

... recipient states clearly on any written questionnaire used for this purpose or makes clear orally, if no... was conditionally placed in a job pool or conditionally placed on an eligibility list prior to the... conditionally in a job pool or conditionally placed on an eligibility list; that is the medical results were the...

29 CFR 32.15 - Preemployment inquiries.

Code of Federal Regulations, 2011 CFR

2011-07-01

... recipient states clearly on any written questionnaire used for this purpose or makes clear orally, if no... was conditionally placed in a job pool or conditionally placed on an eligibility list prior to the... conditionally in a job pool or conditionally placed on an eligibility list; that is the medical results were the...

29 CFR 32.15 - Preemployment inquiries.

Code of Federal Regulations, 2014 CFR

2014-07-01

... on any written questionnaire used for this purpose or makes clear orally, if no written questionnaire... was conditionally placed in a job pool or conditionally placed on an eligibility list prior to the... conditionally in a job pool or conditionally placed on an eligibility list; that is the medical results were the...

3D two-fluid simulations of turbulence in LAPD

NASA Astrophysics Data System (ADS)

Fisher, Dustin M.

The Large Plasma Device (LAPD) is modeled using a modified version of the 3D Global Braginskii Solver code (GBS) for a nominal Helium plasma. The unbiased low-flow regime is explored in simulations where there is an intrinsic E x B rotation of the plasma. In the simulations this rotation is caused primarily by sheath effects with the Reynolds stress and J x B torque due to a cross-field Pederson conductivity having little effect. Explicit biasing simulations are also explored for the first time where the intrinsic rotation of the plasma is modified through boundary conditions that mimic the biasable limiter used in LAPD. Comparisons to experimental measurements in the unbiased case show strong qualitative agreement with the data, particularly the radial dependence of the density fluctuations, cross-correlation lengths, radial flux dependence outside of the cathode edge, and camera imagery. Kelvin Helmholtz (KH) turbulence at relatively large scales is the dominant driver of cross-field transport in these simulations with smaller-scale drift waves and sheath modes playing a secondary role. Plasma holes and blobs arising from KH vortices are consistent with the scale sizes and overall appearance of those in LAPD camera images. The addition of ion-neutral collisions in the unbiased simulations at previously theorized values reduces the radial particle flux due to a modest stabilizing contribution of the collisions on the KH-modes driving the turbulent transport. In the biased runs the ion-neutral collisions have a much smaller effect due to the modification of the potential from sheath terms. In biasing the plasma to increase the intrinsic rotation, simulations show the emergence of a nonlinearly saturated coherent mode of order m = 6. In addition, the plasma inside of the cathode edge becomes quiescent due to the strong influence of the wall bias in setting up the equilibrium plasma potential. Biasing in the direction opposite to the intrinsic flow reduces the effective shear and leads to a stronger presence of drift modes that are seen to saturate when the KH drive has been suppressed. Both biasing cases show a moderate density confinement similarly seen in the experiment.

30 CFR 206.362 - What are my responsibilities to place production into marketable condition and to market production?

Code of Federal Regulations, 2010 CFR

2010-07-01

... production into marketable condition and to market production? 206.362 Section 206.362 Mineral Resources... Geothermal Resources § 206.362 What are my responsibilities to place production into marketable condition and to market production? You must place geothermal resources and byproducts in marketable condition and...

Flood-conditioned place aversion as a novel non-pharmacological aversive learning procedure in mice.

PubMed

Goltseker, Koral; Barak, Segev

2018-05-08

The place conditioning paradigm is an efficient, widely-used method to study mechanisms that underlie appetitive or aversive learning and memory processes. However, pharmacological agents used to induce conditioned place preference (CPP) or aversion (CPA) can per se interfere with learning and memory processing, hence confounding the results. Therefore, non-pharmacological place conditioning procedures are of high importance. Here, we introduce a novel procedure for induction of CPA in mice, by water flooding. We found that pairing a context with immersion in moderately cold shallow water resulted in aversion and avoidance of that context during a place preference test. Importantly, place aversion emerged only when mice experienced the onset of flood during conditioning training, but not when mice were placed in a compartment pre-filled with water. We also found that warm water was not sufficiently aversive to induce CPA. Moreover, CPA was observed after two or three context-flood pairings but not after one or four pairings, suggesting that moderate conditioning intensity produces optimal CPA expression. Thus, flood-induced CPA is a simple, cheap, and efficient procedure to form and measure place aversion memories in mice, using an ethologically-relevant threat.

Lies, Damned Lies, and Survey Self-Reports? Identity as a Cause of Measurement Bias

PubMed Central

Brenner, Philip S.; DeLamater, John

2017-01-01

Explanations of error in survey self-reports have focused on social desirability: that respondents answer questions about normative behavior to appear prosocial to interviewers. However, this paradigm fails to explain why bias occurs even in self-administered modes like mail and web surveys. We offer an alternative explanation rooted in identity theory that focuses on measurement directiveness as a cause of bias. After completing questions about physical exercise on a web survey, respondents completed a text message–based reporting procedure, sending updates on their major activities for five days. Random assignment was then made to one of two conditions: instructions mentioned the focus of the study, physical exercise, or not. Survey responses, text updates, and records from recreation facilities were compared. Direct measures generated bias—overreporting in survey measures and reactivity in the directive text condition—but the nondirective text condition generated unbiased measures. Findings are discussed in terms of identity. PMID:29038609

Decision Processes in Discrimination: Fundamental Misrepresentations of Signal Detection Theory

NASA Technical Reports Server (NTRS)

Balakrishnan, J. D.

1998-01-01

In the first part of this article, I describe a new approach to studying decision making in discrimination tasks that does not depend on the technical assumptions of signal detection theory (e.g., normality of the encoding distributions). Applying these new distribution-free tests to data from three experiments, I show that base rate and payoff manipulations had substantial effects on the participants' encoding distributions but no effect on their decision rules, which were uniformly unbiased in equal and unequal base rate conditions and in symmetric and asymmetric payoff conditions. In the second part of the article, I show that this seemingly paradoxical result is readily explained by the sequential sampling models of discrimination. I then propose a new, "model-free" test for response bias that seems to more properly identify both the nature and direction of the biases induced by the classical bias manipulations.

Drug-induced conditioned place preference and aversion in mice.

PubMed

Cunningham, Christopher L; Gremel, Christina M; Groblewski, Peter A

2006-01-01

This protocol describes the equipment and methods used to establish conditioned place preference (CPP) or aversion (CPA). Place conditioning is a form of Pavlovian conditioning routinely used to measure the rewarding or aversive motivational effects of objects or experiences (e.g., abused drugs). Here, we present a place conditioning procedure that has been used extensively to study the motivational effects of ethanol and other abused drugs in mice. This protocol involves three phases: (i) habituation (or a pretest), (ii) conditioning of an association between the drug and a tactile or visual stimulus and (iii) a test that offers a choice between the drug-associated cue and a neutral cue. If the drug has motivational significance, mice will spend significantly more time (CPP) or less time (CPA) in proximity to the drug-associated cue. Potential problems in the design and interpretation of place conditioning studies are discussed. A typical experiment lasts 2 weeks.

Common Variable Immunodeficiency Non-Infectious Disease Endotypes Redefined Using Unbiased Network Clustering in Large Electronic Datasets.

PubMed

Farmer, Jocelyn R; Ong, Mei-Sing; Barmettler, Sara; Yonker, Lael M; Fuleihan, Ramsay; Sullivan, Kathleen E; Cunningham-Rundles, Charlotte; Walter, Jolan E

2017-01-01

Common variable immunodeficiency (CVID) is increasingly recognized for its association with autoimmune and inflammatory complications. Despite recent advances in immunophenotypic and genetic discovery, clinical care of CVID remains limited by our inability to accurately model risk for non-infectious disease development. Herein, we demonstrate the utility of unbiased network clustering as a novel method to analyze inter-relationships between non-infectious disease outcomes in CVID using databases at the United States Immunodeficiency Network (USIDNET), the centralized immunodeficiency registry of the United States, and Partners, a tertiary care network in Boston, MA, USA, with a shared electronic medical record amenable to natural language processing. Immunophenotypes were comparable in terms of native antibody deficiencies, low titer response to pneumococcus, and B cell maturation arrest. However, recorded non-infectious disease outcomes were more substantial in the Partners cohort across the spectrum of lymphoproliferation, cytopenias, autoimmunity, atopy, and malignancy. Using unbiased network clustering to analyze 34 non-infectious disease outcomes in the Partners cohort, we further identified unique patterns of lymphoproliferative (two clusters), autoimmune (two clusters), and atopic (one cluster) disease that were defined as CVID non-infectious endotypes according to discrete and non-overlapping immunophenotypes. Markers were both previously described {high serum IgE in the atopic cluster [odds ratio (OR) 6.5] and low class-switched memory B cells in the total lymphoproliferative cluster (OR 9.2)} and novel [low serum C3 in the total lymphoproliferative cluster (OR 5.1)]. Mortality risk in the Partners cohort was significantly associated with individual non-infectious disease outcomes as well as lymphoproliferative cluster 2, specifically (OR 5.9). In contrast, unbiased network clustering failed to associate known comorbidities in the adult USIDNET cohort. Together, these data suggest that unbiased network clustering can be used in CVID to redefine non-infectious disease inter-relationships; however, applicability may be limited to datasets well annotated through mechanisms such as natural language processing. The lymphoproliferative, autoimmune, and atopic Partners CVID endotypes herein described can be used moving forward to streamline genetic and biomarker discovery and to facilitate early screening and intervention in CVID patients at highest risk for autoimmune and inflammatory progression.

30 CFR 206.106 - What are my responsibilities to place production into marketable condition and to market production?

Code of Federal Regulations, 2010 CFR

2010-07-01

... production into marketable condition and to market production? 206.106 Section 206.106 Mineral Resources... Federal Oil § 206.106 What are my responsibilities to place production into marketable condition and to market production? You must place oil in marketable condition and market the oil for the mutual benefit...

Mothers adjust offspring sex to match the quality of the rearing environment

PubMed Central

Pryke, Sarah R.; Rollins, Lee A.

2012-01-01

Theory predicts that mothers should adjust offspring sex ratios when the expected fitness gains or rearing costs differ between sons and daughters. Recent empirical work has linked biased offspring sex ratios to environmental quality via changes in relative maternal condition. It is unclear, however, whether females can manipulate offspring sex ratios in response to environmental quality alone (i.e. independent of maternal condition). We used a balanced within-female experimental design (i.e. females bred on both low- and high-quality diets) to show that female parrot finches (Erythrura trichroa) manipulate primary offspring sex ratios to the quality of the rearing environment, and not to their own body condition and health. Individual females produced an unbiased sex ratio on high-quality diets, but over-produced sons in poor dietary conditions, even though they maintained similar condition between diet treatments. Despite the lack of sexual size dimorphism, such sex ratio adjustment is in line with predictions from sex allocation theory because nutritionally stressed foster sons were healthier, grew faster and were more likely to survive than daughters. These findings suggest that mothers may adaptively adjust offspring sex ratios to optimally match their offspring to the expected quality of the rearing environment. PMID:22859597

Mothers adjust offspring sex to match the quality of the rearing environment.

PubMed

Pryke, Sarah R; Rollins, Lee A

2012-10-07

Theory predicts that mothers should adjust offspring sex ratios when the expected fitness gains or rearing costs differ between sons and daughters. Recent empirical work has linked biased offspring sex ratios to environmental quality via changes in relative maternal condition. It is unclear, however, whether females can manipulate offspring sex ratios in response to environmental quality alone (i.e. independent of maternal condition). We used a balanced within-female experimental design (i.e. females bred on both low- and high-quality diets) to show that female parrot finches (Erythrura trichroa) manipulate primary offspring sex ratios to the quality of the rearing environment, and not to their own body condition and health. Individual females produced an unbiased sex ratio on high-quality diets, but over-produced sons in poor dietary conditions, even though they maintained similar condition between diet treatments. Despite the lack of sexual size dimorphism, such sex ratio adjustment is in line with predictions from sex allocation theory because nutritionally stressed foster sons were healthier, grew faster and were more likely to survive than daughters. These findings suggest that mothers may adaptively adjust offspring sex ratios to optimally match their offspring to the expected quality of the rearing environment.

Threat of shock increases excitability and connectivity of the intraparietal sulcus

PubMed Central

Balderston, Nicholas L; Hale, Elizabeth; Hsiung, Abigail; Torrisi, Salvatore; Holroyd, Tom; Carver, Frederick W; Coppola, Richard; Ernst, Monique; Grillon, Christian

2017-01-01

Anxiety disorders affect approximately 1 in 5 (18%) Americans within a given 1 year period, placing a substantial burden on the national health care system. Therefore, there is a critical need to understand the neural mechanisms mediating anxiety symptoms. We used unbiased, multimodal, data-driven, whole-brain measures of neural activity (magnetoencephalography) and connectivity (fMRI) to identify the regions of the brain that contribute most prominently to sustained anxiety. We report that a single brain region, the intraparietal sulcus (IPS), shows both elevated neural activity and global brain connectivity during threat. The IPS plays a key role in attention orienting and may contribute to the hypervigilance that is a common symptom of pathological anxiety. Hyperactivation of this region during elevated state anxiety may account for the paradoxical facilitation of performance on tasks that require an external focus of attention, and impairment of performance on tasks that require an internal focus of attention. DOI: http://dx.doi.org/10.7554/eLife.23608.001 PMID:28555565

Myths and memes about single-payer health insurance in the United States: a rebuttal to conservative claims.

PubMed

Geyman, John P

2005-01-01

Recent years have seen the rapid growth of private think tanks within the neoconservative movement that conduct "policy research" biased to their own agenda. This article provides an evidence-based rebuttal to a 2002 report by one such think tank, the Dallas-based National Center for Policy Analysis (NCPA), which was intended to discredit 20 alleged myths about single-payer national health insurance as a policy option for the United States. Eleven "myths" are rebutted under eight categories: access, cost containment, quality, efficiency, single-payer as solution, control of drug prices, ability to compete abroad (the "business case"), and public support for a single-payer system. Six memes (self-replicating ideas that are promulgated without regard to their merits) are identified in the NCPA report. Myths and memes should have no place in the national debate now underway over the future of a failing health care system, and need to be recognized as such and countered by experience and unbiased evidence.

Detection of seizures from small samples using nonlinear dynamic system theory.

PubMed

Yaylali, I; Koçak, H; Jayakar, P

1996-07-01

The electroencephalogram (EEG), like many other biological phenomena, is quite likely governed by nonlinear dynamics. Certain characteristics of the underlying dynamics have recently been quantified by computing the correlation dimensions (D2) of EEG time series data. In this paper, D2 of the unbiased autocovariance function of the scalp EEG data was used to detect electrographic seizure activity. Digital EEG data were acquired at a sampling rate of 200 Hz per channel and organized in continuous frames (duration 2.56 s, 512 data points). To increase the reliability of D2 computations with short duration data, raw EEG data were initially simplified using unbiased autocovariance analysis to highlight the periodic activity that is present during seizures. The D2 computation was then performed from the unbiased autocovariance function of each channel using the Grassberger-Procaccia method with Theiler's box-assisted correlation algorithm. Even with short duration data, this preprocessing proved to be computationally robust and displayed no significant sensitivity to implementation details such as the choices of embedding dimension and box size. The system successfully identified various types of seizures in clinical studies.

Biased and unbiased perceptual decision-making on vocal emotions.

PubMed

Dricu, Mihai; Ceravolo, Leonardo; Grandjean, Didier; Frühholz, Sascha

2017-11-24

Perceptual decision-making on emotions involves gathering sensory information about the affective state of another person and forming a decision on the likelihood of a particular state. These perceptual decisions can be of varying complexity as determined by different contexts. We used functional magnetic resonance imaging and a region of interest approach to investigate the brain activation and functional connectivity behind two forms of perceptual decision-making. More complex unbiased decisions on affective voices recruited an extended bilateral network consisting of the posterior inferior frontal cortex, the orbitofrontal cortex, the amygdala, and voice-sensitive areas in the auditory cortex. Less complex biased decisions on affective voices distinctly recruited the right mid inferior frontal cortex, pointing to a functional distinction in this region following decisional requirements. Furthermore, task-induced neural connectivity revealed stronger connections between these frontal, auditory, and limbic regions during unbiased relative to biased decision-making on affective voices. Together, the data shows that different types of perceptual decision-making on auditory emotions have distinct patterns of activations and functional coupling that follow the decisional strategies and cognitive mechanisms involved during these perceptual decisions.

Minimum mean squared error (MSE) adjustment and the optimal Tykhonov-Phillips regularization parameter via reproducing best invariant quadratic uniformly unbiased estimates (repro-BIQUUE)

NASA Astrophysics Data System (ADS)

Schaffrin, Burkhard

2008-02-01

In a linear Gauss-Markov model, the parameter estimates from BLUUE (Best Linear Uniformly Unbiased Estimate) are not robust against possible outliers in the observations. Moreover, by giving up the unbiasedness constraint, the mean squared error (MSE) risk may be further reduced, in particular when the problem is ill-posed. In this paper, the α-weighted S-homBLE (Best homogeneously Linear Estimate) is derived via formulas originally used for variance component estimation on the basis of the repro-BIQUUE (reproducing Best Invariant Quadratic Uniformly Unbiased Estimate) principle in a model with stochastic prior information. In the present model, however, such prior information is not included, which allows the comparison of the stochastic approach (α-weighted S-homBLE) with the well-established algebraic approach of Tykhonov-Phillips regularization, also known as R-HAPS (Hybrid APproximation Solution), whenever the inverse of the “substitute matrix” S exists and is chosen as the R matrix that defines the relative impact of the regularizing term on the final result.

Comprehensive Mechanistic Analysis of Hits from High-Throughput and Docking Screens against β-Lactamase

PubMed Central

Babaoglu, Kerim; Simeonov, Anton; Irwin, John J.; Nelson, Michael E.; Feng, Brian; Thomas, Craig J.; Cancian, Laura; Costi, M. Paola; Maltby, David A.; Jadhav, Ajit; Inglese, James; Austin, Christopher P.; Shoichet, Brian K.

2009-01-01

High-throughput screening (HTS) is widely used in drug discovery. Especially for screens of unbiased libraries, false positives can dominate “hit lists”; their origins are much debated. Here we determine the mechanism of every active hit from a screen of 70,563 unbiased molecules against β-lactamase using quantitative HTS (qHTS). Of the 1274 initial inhibitors, 95% were detergent-sensitive and were classified as aggregators. Among the 70 remaining were 25 potent, covalent-acting β-lactams. Mass spectra, counter-screens, and crystallography identified 12 as promiscuous covalent inhibitors. The remaining 33 were either aggregators or irreproducible. No specific reversible inhibitors were found. We turned to molecular docking to prioritize molecules from the same library for testing at higher concentrations. Of 16 tested, 2 were modest inhibitors. Subsequent X-ray structures corresponded to the docking prediction. Analog synthesis improved affinity to 8 µM. These results suggest that it may be the physical behavior of organic molecules, not their reactivity, that accounts for most screening artifacts. Structure-based methods may prioritize weak-but-novel chemotypes in unbiased library screens. PMID:18333608

Construction of mutually unbiased bases with cyclic symmetry for qubit systems

DOE Office of Scientific and Technical Information (OSTI.GOV)

Seyfarth, Ulrich; Ranade, Kedar S.

2011-10-15

For the complete estimation of arbitrary unknown quantum states by measurements, the use of mutually unbiased bases has been well established in theory and experiment for the past 20 years. However, most constructions of these bases make heavy use of abstract algebra and the mathematical theory of finite rings and fields, and no simple and generally accessible construction is available. This is particularly true in the case of a system composed of several qubits, which is arguably the most important case in quantum information science and quantum computation. In this paper, we close this gap by providing a simple andmore » straightforward method for the construction of mutually unbiased bases in the case of a qubit register. We show that our construction is also accessible to experiments, since only Hadamard and controlled-phase gates are needed, which are available in most practical realizations of a quantum computer. Moreover, our scheme possesses the optimal scaling possible, i.e., the number of gates scales only linearly in the number of qubits.« less

Efficiency optimization in a correlation ratchet with asymmetric unbiased fluctuations

NASA Astrophysics Data System (ADS)

Ai, Bao-Quan; Wang, Xian-Ju; Liu, Guo-Tao; Wen, De-Hua; Xie, Hui-Zhang; Chen, Wei; Liu, Liang-Gang

2003-12-01

The efficiency of a Brownian particle moving in a periodic potential in the presence of asymmetric unbiased fluctuations is investigated. We found that even on the quasistatic limit there is a regime where the efficiency can be a peaked function of temperature, which proves that thermal fluctuations facilitate the efficiency of energy transformation, contradicting the earlier findings [H. Kamegawa et al., Phys. Rev. Lett. 80, 5251 (1998)]. It is also found that the mutual interplay between temporal asymmetry and spatial asymmetry may induce optimized efficiency at finite temperatures. The ratchet is not most efficient when it gives maximum current.

Quasi interpolation with Voronoi splines.

PubMed

Mirzargar, Mahsa; Entezari, Alireza

2011-12-01

We present a quasi interpolation framework that attains the optimal approximation-order of Voronoi splines for reconstruction of volumetric data sampled on general lattices. The quasi interpolation framework of Voronoi splines provides an unbiased reconstruction method across various lattices. Therefore this framework allows us to analyze and contrast the sampling-theoretic performance of general lattices, using signal reconstruction, in an unbiased manner. Our quasi interpolation methodology is implemented as an efficient FIR filter that can be applied online or as a preprocessing step. We present visual and numerical experiments that demonstrate the improved accuracy of reconstruction across lattices, using the quasi interpolation framework. © 2011 IEEE

Precision medicine in the age of big data: The present and future role of large-scale unbiased sequencing in drug discovery and development.

PubMed

Vicini, P; Fields, O; Lai, E; Litwack, E D; Martin, A-M; Morgan, T M; Pacanowski, M A; Papaluca, M; Perez, O D; Ringel, M S; Robson, M; Sakul, H; Vockley, J; Zaks, T; Dolsten, M; Søgaard, M

2016-02-01

High throughput molecular and functional profiling of patients is a key driver of precision medicine. DNA and RNA characterization has been enabled at unprecedented cost and scale through rapid, disruptive progress in sequencing technology, but challenges persist in data management and interpretation. We analyze the state-of-the-art of large-scale unbiased sequencing in drug discovery and development, including technology, application, ethical, regulatory, policy and commercial considerations, and discuss issues of LUS implementation in clinical and regulatory practice. © 2015 American Society for Clinical Pharmacology and Therapeutics.

Unbiased and robust quantification of synchronization between spikes and local field potential.

PubMed

Li, Zhaohui; Cui, Dong; Li, Xiaoli

2016-08-30

In neuroscience, relating the spiking activity of individual neurons to the local field potential (LFP) of neural ensembles is an increasingly useful approach for studying rhythmic neuronal synchronization. Many methods have been proposed to measure the strength of the association between spikes and rhythms in the LFP recordings, and most existing measures are dependent upon the total number of spikes. In the present work, we introduce a robust approach for quantifying spike-LFP synchronization which performs reliably for limited samples of data. The measure is termed as spike-triggered correlation matrix synchronization (SCMS), which takes LFP segments centered on each spike as multi-channel signals and calculates the index of spike-LFP synchronization by constructing a correlation matrix. The simulation based on artificial data shows that the SCMS output almost does not change with the sample size. This property is of crucial importance when making comparisons between different experimental conditions. When applied to actual neuronal data recorded from the monkey primary visual cortex, it is found that the spike-LFP synchronization strength shows orientation selectivity to drifting gratings. In comparison to another unbiased method, pairwise phase consistency (PPC), the proposed SCMS behaves better for noisy spike trains by means of numerical simulations. This study demonstrates the basic idea and calculating process of the SCMS method. Considering its unbiasedness and robustness, the measure is of great advantage to characterize the synchronization between spike trains and rhythms present in LFP. Copyright © 2016 Elsevier B.V. All rights reserved.

Kolmogorov-Smirnov test for spatially correlated data

USGS Publications Warehouse

Olea, R.A.; Pawlowsky-Glahn, V.

2009-01-01

The Kolmogorov-Smirnov test is a convenient method for investigating whether two underlying univariate probability distributions can be regarded as undistinguishable from each other or whether an underlying probability distribution differs from a hypothesized distribution. Application of the test requires that the sample be unbiased and the outcomes be independent and identically distributed, conditions that are violated in several degrees by spatially continuous attributes, such as topographical elevation. A generalized form of the bootstrap method is used here for the purpose of modeling the distribution of the statistic D of the Kolmogorov-Smirnov test. The innovation is in the resampling, which in the traditional formulation of bootstrap is done by drawing from the empirical sample with replacement presuming independence. The generalization consists of preparing resamplings with the same spatial correlation as the empirical sample. This is accomplished by reading the value of unconditional stochastic realizations at the sampling locations, realizations that are generated by simulated annealing. The new approach was tested by two empirical samples taken from an exhaustive sample closely following a lognormal distribution. One sample was a regular, unbiased sample while the other one was a clustered, preferential sample that had to be preprocessed. Our results show that the p-value for the spatially correlated case is always larger that the p-value of the statistic in the absence of spatial correlation, which is in agreement with the fact that the information content of an uncorrelated sample is larger than the one for a spatially correlated sample of the same size. ?? Springer-Verlag 2008.

Express path analysis identifies a tyrosine kinase Src-centric network regulating divergent host responses to Mycobacterium tuberculosis infection.

PubMed

Karim, Ahmad Faisal; Chandra, Pallavi; Chopra, Aanchal; Siddiqui, Zaved; Bhaskar, Ashima; Singh, Amit; Kumar, Dhiraj

2011-11-18

Global gene expression profiling has emerged as a major tool in understanding complex response patterns of biological systems to perturbations. However, a lack of unbiased analytical approaches has restricted the utility of complex microarray data to gain novel system level insights. Here we report a strategy, express path analysis (EPA), that helps to establish various pathways differentially recruited to achieve specific cellular responses under contrasting environmental conditions in an unbiased manner. The analysis superimposes differentially regulated genes between contrasting environments onto the network of functional protein associations followed by a series of iterative enrichments and network analysis. To test the utility of the approach, we infected THP1 macrophage cells with a virulent Mycobacterium tuberculosis strain (H37Rv) or the attenuated non-virulent strain H37Ra as contrasting perturbations and generated the temporal global expression profiles. EPA of the results provided details of response-specific and time-dependent host molecular network perturbations. Further analysis identified tyrosine kinase Src as the major regulatory hub discriminating the responses between wild-type and attenuated Mtb infection. We were then able to verify this novel role of Src experimentally and show that Src executes its role through regulating two vital antimicrobial processes of the host cells (i.e. autophagy and acidification of phagolysosome). These results bear significant potential for developing novel anti-tuberculosis therapy. We propose that EPA could prove extremely useful in understanding complex cellular responses for a variety of perturbations, including pathogenic infections.

On using scatterometer and altimeter data to improve storm surge forecasting in the Adriatic Sea

NASA Astrophysics Data System (ADS)

Bajo, Marco; Umgiesser, Georg; De Biasio, Francesco; Vignudelli, Stefano; Zecchetto, Stefano

2017-04-01

Satellite data are seldom used in storm surge forecasting. Among the most important issues related to the storm surge forecasting are the quality of the model wind forcing and the initial condition of the sea surface elevation. In this work, focused on storm surge forecasting in the Adriatic Sea, satellite scatterometer wind data are used to correct the wind speed and direction biases of the ECMWF global atmospheric model by tuning the spatial fields, as an alternative to data assimilation. The capability of such an unbiased wind is tested against that of a high resolution wind, produced by a regional non-hydrostatic model. On the other hand, altimeter Total Water Level Envelope (TWLE) data, which provide the sea level elevation, are used to improve the accuracy of the initial state of the model simulations. This is done by assimilating into a storm surge model the TWLE obtained by the altimeter observations along ground tracks, after subtraction of the tidal components. In order to test the methodology, eleven storm surge events recorded in Venice, from 2008 to 2012, have been simulated using different configurations of forcing wind and altimeter data assimilation. Results show that the relative error on the estimation of the maximum surge peak, averaged over the cases considered, decreases from 13% to 7% using both the unbiased wind and the altimeter data assimilation, while forcing the hydrodynamic model with the high resolution wind (no tuning), the altimeter data assimilation reduces the error from 9% to 6%.

Beyond total treatment effects in randomised controlled trials: Baseline measurement of intermediate outcomes needed to reduce confounding in mediation investigations.

PubMed

Landau, Sabine; Emsley, Richard; Dunn, Graham

2018-06-01

Random allocation avoids confounding bias when estimating the average treatment effect. For continuous outcomes measured at post-treatment as well as prior to randomisation (baseline), analyses based on (A) post-treatment outcome alone, (B) change scores over the treatment phase or (C) conditioning on baseline values (analysis of covariance) provide unbiased estimators of the average treatment effect. The decision to include baseline values of the clinical outcome in the analysis is based on precision arguments, with analysis of covariance known to be most precise. Investigators increasingly carry out explanatory analyses to decompose total treatment effects into components that are mediated by an intermediate continuous outcome and a non-mediated part. Traditional mediation analysis might be performed based on (A) post-treatment values of the intermediate and clinical outcomes alone, (B) respective change scores or (C) conditioning on baseline measures of both intermediate and clinical outcomes. Using causal diagrams and Monte Carlo simulation, we investigated the performance of the three competing mediation approaches. We considered a data generating model that included three possible confounding processes involving baseline variables: The first two processes modelled baseline measures of the clinical variable or the intermediate variable as common causes of post-treatment measures of these two variables. The third process allowed the two baseline variables themselves to be correlated due to past common causes. We compared the analysis models implied by the competing mediation approaches with this data generating model to hypothesise likely biases in estimators, and tested these in a simulation study. We applied the methods to a randomised trial of pragmatic rehabilitation in patients with chronic fatigue syndrome, which examined the role of limiting activities as a mediator. Estimates of causal mediation effects derived by approach (A) will be biased if one of the three processes involving baseline measures of intermediate or clinical outcomes is operating. Necessary assumptions for the change score approach (B) to provide unbiased estimates under either process include the independence of baseline measures and change scores of the intermediate variable. Finally, estimates provided by the analysis of covariance approach (C) were found to be unbiased under all the three processes considered here. When applied to the example, there was evidence of mediation under all methods but the estimate of the indirect effect depended on the approach used with the proportion mediated varying from 57% to 86%. Trialists planning mediation analyses should measure baseline values of putative mediators as well as of continuous clinical outcomes. An analysis of covariance approach is recommended to avoid potential biases due to confounding processes involving baseline measures of intermediate or clinical outcomes, and not simply for increased precision.

A spatially explicit capture-recapture estimator for single-catch traps.

PubMed

Distiller, Greg; Borchers, David L

2015-11-01

Single-catch traps are frequently used in live-trapping studies of small mammals. Thus far, a likelihood for single-catch traps has proven elusive and usually the likelihood for multicatch traps is used for spatially explicit capture-recapture (SECR) analyses of such data. Previous work found the multicatch likelihood to provide a robust estimator of average density. We build on a recently developed continuous-time model for SECR to derive a likelihood for single-catch traps. We use this to develop an estimator based on observed capture times and compare its performance by simulation to that of the multicatch estimator for various scenarios with nonconstant density surfaces. While the multicatch estimator is found to be a surprisingly robust estimator of average density, its performance deteriorates with high trap saturation and increasing density gradients. Moreover, it is found to be a poor estimator of the height of the detection function. By contrast, the single-catch estimators of density, distribution, and detection function parameters are found to be unbiased or nearly unbiased in all scenarios considered. This gain comes at the cost of higher variance. If there is no interest in interpreting the detection function parameters themselves, and if density is expected to be fairly constant over the survey region, then the multicatch estimator performs well with single-catch traps. However if accurate estimation of the detection function is of interest, or if density is expected to vary substantially in space, then there is merit in using the single-catch estimator when trap saturation is above about 60%. The estimator's performance is improved if care is taken to place traps so as to span the range of variables that affect animal distribution. As a single-catch likelihood with unknown capture times remains intractable for now, researchers using single-catch traps should aim to incorporate timing devices with their traps.

77 FR 16910 - Special Conditions: Boeing Model 787 Series Airplanes; Single-place Side-facing Seats With...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-23

...-0311; Special Conditions No. 25-458-SC] Special Conditions: Boeing Model 787 Series Airplanes; Single... associated with single-place side-facing seats with inflatable lapbelts. The applicable airworthiness... have a novel or unusual design feature associated with single-place side-facing seats with inflatable...

Determinants of Hospital Death for Taiwanese Pediatric Cancer Decedents, 2001-2010.

PubMed

Hung, Yen-Ni; Liu, Tsang-Wu; Tang, Siew Tzuh

2015-11-01

Factors influencing pediatric cancer patients' place of death may have evolved with advances in medical and hospice care since earlier studies were done. To comprehensively analyze factors associated with hospital death in an unbiased population of pediatric cancer patients in Taiwan. This was a retrospective cohort study using administrative data for 1603 Taiwanese pediatric cancer patients who died in 2001-2010. Place of death was hypothesized to be associated with 1) patient sociodemographics and disease characteristics, 2) primary physician's specialty, 3) characteristics and health care resources at both the hospital and regional levels, and 4) historical trends. Most Taiwanese pediatric cancer patients (87.4%) died in an acute care hospital. The probability of dying in hospital increased slightly over time, reaching significance only in 2009 (adjusted odds ratio [AOR], 95% CI: 2.84 [1.32-6.11]). Children were more likely to die in an acute care hospital if they resided in the most urbanized area, were diagnosed with leukemia or lymphoma (2.32 [1.39-3.87]), and received care from a pediatrician (1.58 [1.01-2.47]) in a nonprofit proprietary hospital (1.50 [1.01-2.24]) or large hospital, reaching significance for the third quartile (2.57 [1.28-5.18]) of acute care hospital beds. Taiwanese pediatric cancer patients predominantly died in an acute care hospital with a slightly increasing trend of shifting place of death from home to hospital. Propensity for hospital death was determined by residential urbanization level, diagnosis, primary physician's specialty, and the primary hospital's characteristics and health care resources. Clinical interventions and health policies should ensure that resources are allocated to allow pediatric cancer patients to die in the place they and their parents prefer to achieve a good death and promote their parents' bereavement adjustment. Copyright © 2015 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

Buprenorphine and a CRF1 antagonist block the acquisition of opiate withdrawal-induced conditioned place aversion in rats.

PubMed

Stinus, Luis; Cador, Martine; Zorrilla, Eric P; Koob, George F

2005-01-01

Conditioned place aversion in rats has face validity as a measure of the aversive stimulus effects of opiate withdrawal that reflects an important motivational component of opiate dependence. The purpose of the present study was to validate conditioned place aversion as sensitive to medications that will alleviate the aversive stimulus effects of opiate withdrawal in humans, and to extend this model to the exploration of the neuropharmacological basis of the motivational effects of opiate withdrawal. Male Sprague-Dawley rats were implanted with two subcutaneous morphine pellets and 5 days later began place conditioning training following subcutaneous administration of a low dose of naloxone. Animals were subjected to three pairings of a low dose of naloxone (15 microg/kg, s.c.) to one arm of a three-chambered place conditioning apparatus. Buprenorphine administered prior to each pairing dose-dependently blocked the place aversion produced by precipitated opiate withdrawal. A corticotropin-releasing factor-1 (CRF1) receptor antagonist (antalarmin) also reversed the place aversion produced by precipitated opiate withdrawal. Antalarmin did not produce a place preference or place aversion by itself in morphine-dependent rats. No effect was observed with pretreatment of the dopamine partial agonist terguride or the selective serotonin reuptake inhibitor fluoxetine. Also, chronic pretreatment with acamprosate (a glutamate receptor modulator used to prevent relapse in alcohol dependence) did not alter naloxone-induced place aversion. Buprenorphine by itself in dependent rats produced a mild place preference at low doses and a mild place aversion at higher doses. These results suggest that buprenorphine blocks the aversive stimulus effects of precipitated opiate withdrawal in rats and provides some validity for the use of place conditioning as a measure that is sensitive to potential opiate-dependence medications. In addition, these results suggest that CRF1 antagonists can block the aversive stimulus effects of opiate withdrawal and may be potential therapeutic targets for opiate dependence.

Epidemiologic research using probabilistic outcome definitions.

PubMed

Cai, Bing; Hennessy, Sean; Lo Re, Vincent; Small, Dylan S

2015-01-01

Epidemiologic studies using electronic healthcare data often define the presence or absence of binary clinical outcomes by using algorithms with imperfect specificity, sensitivity, and positive predictive value. This results in misclassification and bias in study results. We describe and evaluate a new method called probabilistic outcome definition (POD) that uses logistic regression to estimate the probability of a clinical outcome using multiple potential algorithms and then uses multiple imputation to make valid inferences about the risk ratio or other epidemiologic parameters of interest. We conducted a simulation to evaluate the performance of the POD method with two variables that can predict the true outcome and compared the POD method with the conventional method. The simulation results showed that when the true risk ratio is equal to 1.0 (null), the conventional method based on a binary outcome provides unbiased estimates. However, when the risk ratio is not equal to 1.0, the traditional method, either using one predictive variable or both predictive variables to define the outcome, is biased when the positive predictive value is <100%, and the bias is very severe when the sensitivity or positive predictive value is poor (less than 0.75 in our simulation). In contrast, the POD method provides unbiased estimates of the risk ratio both when this measure of effect is equal to 1.0 and not equal to 1.0. Even when the sensitivity and positive predictive value are low, the POD method continues to provide unbiased estimates of the risk ratio. The POD method provides an improved way to define outcomes in database research. This method has a major advantage over the conventional method in that it provided unbiased estimates of risk ratios and it is easy to use. Copyright © 2014 John Wiley & Sons, Ltd.

Estimating Unbiased Land Cover Change Areas In The Colombian Amazon Using Landsat Time Series And Statistical Inference Methods

NASA Astrophysics Data System (ADS)

Arevalo, P. A.; Olofsson, P.; Woodcock, C. E.

2017-12-01

Unbiased estimation of the areas of conversion between land categories ("activity data") and their uncertainty is crucial for providing more robust calculations of carbon emissions to the atmosphere, as well as their removals. This is particularly important for the REDD+ mechanism of UNFCCC where an economic compensation is tied to the magnitude and direction of such fluxes. Dense time series of Landsat data and statistical protocols are becoming an integral part of forest monitoring efforts, but there are relatively few studies in the tropics focused on using these methods to advance operational MRV systems (Monitoring, Reporting and Verification). We present the results of a prototype methodology for continuous monitoring and unbiased estimation of activity data that is compliant with the IPCC Approach 3 for representation of land. We used a break detection algorithm (Continuous Change Detection and Classification, CCDC) to fit pixel-level temporal segments to time series of Landsat data in the Colombian Amazon. The segments were classified using a Random Forest classifier to obtain annual maps of land categories between 2001 and 2016. Using these maps, a biannual stratified sampling approach was implemented and unbiased stratified estimators constructed to calculate area estimates with confidence intervals for each of the stable and change classes. Our results provide evidence of a decrease in primary forest as a result of conversion to pastures, as well as increase in secondary forest as pastures are abandoned and the forest allowed to regenerate. Estimating areas of other land transitions proved challenging because of their very small mapped areas compared to stable classes like forest, which corresponds to almost 90% of the study area. Implications on remote sensing data processing, sample allocation and uncertainty reduction are also discussed.

Constructing statistically unbiased cortical surface templates using feature-space covariance

NASA Astrophysics Data System (ADS)

Parvathaneni, Prasanna; Lyu, Ilwoo; Huo, Yuankai; Blaber, Justin; Hainline, Allison E.; Kang, Hakmook; Woodward, Neil D.; Landman, Bennett A.

2018-03-01

The choice of surface template plays an important role in cross-sectional subject analyses involving cortical brain surfaces because there is a tendency toward registration bias given variations in inter-individual and inter-group sulcal and gyral patterns. In order to account for the bias and spatial smoothing, we propose a feature-based unbiased average template surface. In contrast to prior approaches, we factor in the sample population covariance and assign weights based on feature information to minimize the influence of covariance in the sampled population. The mean surface is computed by applying the weights obtained from an inverse covariance matrix, which guarantees that multiple representations from similar groups (e.g., involving imaging, demographic, diagnosis information) are down-weighted to yield an unbiased mean in feature space. Results are validated by applying this approach in two different applications. For evaluation, the proposed unbiased weighted surface mean is compared with un-weighted means both qualitatively and quantitatively (mean squared error and absolute relative distance of both the means with baseline). In first application, we validated the stability of the proposed optimal mean on a scan-rescan reproducibility dataset by incrementally adding duplicate subjects. In the second application, we used clinical research data to evaluate the difference between the weighted and unweighted mean when different number of subjects were included in control versus schizophrenia groups. In both cases, the proposed method achieved greater stability that indicated reduced impacts of sampling bias. The weighted mean is built based on covariance information in feature space as opposed to spatial location, thus making this a generic approach to be applicable to any feature of interest.

Toward high-throughput phenotyping: unbiased automated feature extraction and selection from knowledge sources.

PubMed

Yu, Sheng; Liao, Katherine P; Shaw, Stanley Y; Gainer, Vivian S; Churchill, Susanne E; Szolovits, Peter; Murphy, Shawn N; Kohane, Isaac S; Cai, Tianxi

2015-09-01

Analysis of narrative (text) data from electronic health records (EHRs) can improve population-scale phenotyping for clinical and genetic research. Currently, selection of text features for phenotyping algorithms is slow and laborious, requiring extensive and iterative involvement by domain experts. This paper introduces a method to develop phenotyping algorithms in an unbiased manner by automatically extracting and selecting informative features, which can be comparable to expert-curated ones in classification accuracy. Comprehensive medical concepts were collected from publicly available knowledge sources in an automated, unbiased fashion. Natural language processing (NLP) revealed the occurrence patterns of these concepts in EHR narrative notes, which enabled selection of informative features for phenotype classification. When combined with additional codified features, a penalized logistic regression model was trained to classify the target phenotype. The authors applied our method to develop algorithms to identify patients with rheumatoid arthritis and coronary artery disease cases among those with rheumatoid arthritis from a large multi-institutional EHR. The area under the receiver operating characteristic curves (AUC) for classifying RA and CAD using models trained with automated features were 0.951 and 0.929, respectively, compared to the AUCs of 0.938 and 0.929 by models trained with expert-curated features. Models trained with NLP text features selected through an unbiased, automated procedure achieved comparable or slightly higher accuracy than those trained with expert-curated features. The majority of the selected model features were interpretable. The proposed automated feature extraction method, generating highly accurate phenotyping algorithms with improved efficiency, is a significant step toward high-throughput phenotyping. © The Author 2015. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Estimating genetic effects and quantifying missing heritability explained by identified rare-variant associations.

PubMed

Liu, Dajiang J; Leal, Suzanne M

2012-10-05

Next-generation sequencing has led to many complex-trait rare-variant (RV) association studies. Although single-variant association analysis can be performed, it is grossly underpowered. Therefore, researchers have developed many RV association tests that aggregate multiple variant sites across a genetic region (e.g., gene), and test for the association between the trait and the aggregated genotype. After these aggregate tests detect an association, it is only possible to estimate the average genetic effect for a group of RVs. As a result of the "winner's curse," such an estimate can be biased. Although for common variants one can obtain unbiased estimates of genetic parameters by analyzing a replication sample, for RVs it is desirable to obtain unbiased genetic estimates for the study where the association is identified. This is because there can be substantial heterogeneity of RV sites and frequencies even among closely related populations. In order to obtain an unbiased estimate for aggregated RV analysis, we developed bootstrap-sample-split algorithms to reduce the bias of the winner's curse. The unbiased estimates are greatly important for understanding the population-specific contribution of RVs to the heritability of complex traits. We also demonstrate both theoretically and via simulations that for aggregate RV analysis the genetic variance for a gene or region will always be underestimated, sometimes substantially, because of the presence of noncausal variants or because of the presence of causal variants with effects of different magnitudes or directions. Therefore, even if RVs play a major role in the complex-trait etiologies, a portion of the heritability will remain missing, and the contribution of RVs to the complex-trait etiologies will be underestimated. Copyright © 2012 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Independent technical review and analysis of hydraulic modeling and hydrology under low-flow conditions of the Des Plaines River near Riverside, Illinois

USGS Publications Warehouse

Over, Thomas M.; Straub, Timothy D.; Hortness, Jon E.; Murphy, Elizabeth A.

2012-01-01

The U.S. Geological Survey (USGS) has operated a streamgage and published daily flows for the Des Plaines River at Riverside since Oct. 1, 1943. A HEC-RAS model has been developed to estimate the effect of the removal of Hofmann Dam near the gage on low-flow elevations in the reach approximately 3 miles upstream from the dam. The Village of Riverside, the Illinois Department of Natural Resources-Office of Water Resources (IDNR-OWR), and the U. S. Army Corps of Engineers-Chicago District (USACE-Chicago) are interested in verifying the performance of the HEC-RAS model for specific low-flow conditions, and obtaining an estimate of selected daily flow quantiles and other low-flow statistics for a selected period of record that best represents current hydrologic conditions. Because the USGS publishes streamflow records for the Des Plaines River system and provides unbiased analyses of flows and stream hydraulic characteristics, the USGS served as an Independent Technical Reviewer (ITR) for this study.

Lineup administrator influences on eyewitness identification decisions.

PubMed

Clark, Steven E; Marshall, Tanya E; Rosenthal, Robert

2009-03-01

The present research examines how a lineup administrator may influence eyewitness identification decisions through different forms of influence, after providing the witness with standard, unbiased instructions. Participant-witnesses viewed a staged crime and were later shown a target-present or target-absent lineup. The lineup administrators either remained silent while the witness examined the lineup, made ostensibly cautionary statements to the witness, or prompted the witness to identify the person in the lineup who seemed most similar to the perpetrator. These two forms of influence, denoted as subtle-influence and similarity-influence conditions, led to different patterns of identification results. Results for the similarity-influence condition were generally consistent with criterion shift and relative judgment models of eyewitness decision making. Results for the subtle-influence condition, however, cannot be explained by alterations in the decision rule. A weighted matching model is outlined to explain results from the subtle-influence condition. Witnesses seemed generally unaware of the attempts by the lineup administrator to influence their decision, although some noted it, and the probative value of suspect identifications was lower for those who did note it. Implications for theory and policy are discussed. (PsycINFO Database Record (c) 2009 APA, all rights reserved).

Taking one’s time in feeling other-race pain: an event-related potential investigation on the time-course of cross-racial empathy

PubMed Central

Meconi, Federica; Castelli, Luigi; Dell’Acqua, Roberto

2014-01-01

Using the event-related potential (ERP) approach, we tracked the time-course of white participants’ empathic reactions to white (own-race) and black (other-race) faces displayed in a painful condition (i.e. with a needle penetrating the skin) and in a nonpainful condition (i.e. with Q-tip touching the skin). In a 280–340 ms time-window, neural responses to the pain of own-race individuals under needle penetration conditions were amplified relative to neural responses to the pain of other-race individuals displayed under analogous conditions. This ERP reaction to pain, whose source was localized in the inferior frontal gyrus, correlated with the empathic concern ratings of the Interpersonal Reactivity Index questionnaire. In a 400–750 ms time-window, the difference between neural reactions to the pain of own-race individuals, localized in the middle frontal gyrus and other-race individuals, localized in the temporoparietal junction was reduced to nil. These findings support a functional, neural and temporal distinction between two sequential processing stages underlying empathy, namely, a race-biased stage of pain sharing/mirroring followed by a race-unbiased stage of cognitive evaluation of pain. PMID:23314008

Pavlovian conditioning of multiple opioid-like responses in mice.

PubMed

Bryant, Camron D; Roberts, Kristofer W; Culbertson, Christopher S; Le, Alan; Evans, Christopher J; Fanselow, Michael S

2009-07-01

Conditional responses in rodents such as locomotion have been reported for drugs of abuse and similar to the placebo response in humans, may be associated with the expectation of reward. We examined several conditional opioid-like responses and the influence of drug expectation on conditioned place preference and concomitant conditional locomotion. Male C57BL/6J mice were conditioned with the selective mu opioid receptor agonist fentanyl (0.2mg/kg, i.p.) in a novel context and subsequently given a vehicle injection. In separate experiments, locomotor activity, Straub tail, hot plate sensitivity, and conditioned place preference (CPP) were measured. Mice exhibited multiple conditional opioid-like responses including conditional hyperlocomotion, a conditional pattern of opioid-like locomotion, Straub tail, analgesia, and place preference. Modulating drug expectation via administration of fentanyl to "demonstrator" mice in the home cage did not affect the expression of conditioned place preference or the concomitant locomotor activity in "observer" mice. In summary, Pavlovian conditioning of an opioid in a novel context induced multiple conditional opioid-like behaviors and provides a model for studying the neurobiological mechanisms of the placebo response in mice.

Differential effects of 5-HT2C receptor activation by WAY 161503 on nicotine-induced place conditioning and locomotor activity in rats.

PubMed

Hayes, Dave J; Mosher, Tera M; Greenshaw, Andrew J

2009-02-11

Numerous studies indicate a role for both the serotonin 2C receptor (5-HT(2C)) and the nicotinic acetylcholine receptor in locomotion, reinforcement and motivated behaviours. Nicotine, a potent nicotinic acetylcholine receptor agonist, interacts with the dopaminergic and serotonergic systems and is known to positively affect reward-related behaviours. The current study examined the effects of 5-HT(2C) receptor activation on nicotine-induced (0.6 mg/kg) place conditioning and spontaneous locomotion. Using Sprague-Dawley rats, the effects of the selective 5-HT(2C) receptor agonist WAY 161503 (0-1.0 mg/kg) and the selective 5-HT(2C) receptor antagonist SB 242084 (1.0 mg/kg) alone, in combination, and on nicotine-induced (0.6 mg/kg) spontaneous locomotor activity were assessed. The effects of WAY 161503 (1.0, 3.0 mg/kg) were also investigated in nicotine-induced place conditioning using a two-compartment biased design; amphetamine (1.0 mg/kg) served as a positive control. As differential effects were observed between place conditioning and locomotor activity, the subjects used in the place conditioning experiments were also tested for effects on locomotor activity. WAY 161503 decreased baseline and nicotine-induced locomotor activity at the highest dose tested (1.0mg/kg) and these effects were attenuated by SB 242084. Amphetamine and nicotine both induced robust place preferences and WAY 161503 did not have any effects in the context of place conditioning. In contrast, WAY 161503 (1.0 mg/kg) blocked nicotine-induced locomotor activity. These results suggest that 5-HT(2C) receptors may play an inhibitory role in nicotine-induced locomotor activity, but do not appear to influence place conditioning under the current conditions.

Place and contingency differential responses of monkey septal neurons during conditional place-object discrimination.

PubMed

Kita, T; Nishijo, H; Eifuku, S; Terasawa, K; Ono, T

1995-03-01

To elucidate spatial and cognitive function of the septal nuclei, neural activity was recorded from alert monkeys during performance of a place-dependent go/no-go (PGN) task. Response/reinforcement contingencies of given objects were conditional upon the location of a motorized, movable device (cab) containing a monkey in one of four places. The task was initiated by presentation of the outside view (place phase) followed by presentation of an object (object phase) selected from a total of four. A lever press was reinforced only if the correct object was seen in its corresponding place, and the same object was never reinforced in any of the other three places. Of 430 septal neurons recorded, the responses during the place phase in the four places were significantly different in 58 neurons. Responses of eight of these neurons were also place-differential during the object phase as well as the place phase. Furthermore, when the outside view was not presented before the object phase, differential responses in the object phase disappeared. Responses of 91 neurons in the object phase were differential in terms of go/no-go responses and reward availability. Of these 91 neurons, 72 were further tested on a place-independent asymmetrical go/no-go (AGN) task, which required no conditional discrimination. Forty-three neurons responded differentially only in the PGN task. It is thus concluded that this PGN-specific activity reflected conditional place-object relations. Of the remaining 29 neurons that responded differentially in both tasks, 21 were further tested by a place-independent symmetrical go/no-go task (no-go responses were also rewarded). Responses of 19 of these 21 neurons were related to the reward/nonreward contingency but not to the response contingency. The results suggest that septal nuclei are involved in integrating spatial information, conditional place-object relations, and reward/nonreward contingency.

Differential Estimates of Southern Flying Squirrel (Glaucomys volans) Population Structure Based on Capture Method.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Laves, Kevin S.; Loeb, Susan C.

2006-01-01

ABSTRACT.—It is commonly assumed that population estimates derived from trapping small mammals are accurate and unbiased or that estimates derived from different capture methods are comparable. We captured southern flying squirrels (Glaucomys volans) using two methods to study their effect on red-cockaded woodpecker (Picoides borealis) reproductive success. Southern flying squirrels were captured at and removed from 30 red-cockaded woodpecker cluster sites during March to July 1994 and 1995 using Sherman traps placed in a grid encompassing a red-cockaded woodpecker nest tree and by hand from red-cockaded woodpecker cavities. Totals of 195 (1994) and 190 (1995) red-cockaded woodpecker cavities were examinedmore » at least three times each year. Trappability of southern flying squirrels in Sherman traps was significantly greater in 1995 (1.18%; 22,384 trap nights) than in 1994 (0.42%; 20,384 trap nights), and capture rate of southern flying squirrels in cavities was significantly greater in 1994 (22.7%; 502 cavity inspections) than in 1995 (10.8%; 555 cavity inspections). However, more southern flying squirrels were captured per cavity inspection than per Sherman trap night in both years. Male southern flying squirrels were more likely to be captured from cavities than in Sherman traps in 1994, but not in 1995. Both male and female juveniles were more likely to be captured in cavities than in traps in both years. In 1994 males in reproductive condition were more likely to be captured in cavities than in traps and in 1995 we captured significantly more reproductive females in cavities than in traps. Our data suggest that population estimates based solely on one trapping method may not represent true population size or structure of southern flying squirrels.« less

In vivo interactions between α7 nicotinic acetylcholine receptor and nuclear peroxisome proliferator-activated receptor-α: Implication for nicotine dependence.

PubMed

Jackson, Asti; Bagdas, Deniz; Muldoon, Pretal P; Lichtman, Aron H; Carroll, F Ivy; Greenwald, Mark; Miles, Michael F; Damaj, M Imad

2017-05-15

Chronic tobacco use dramatically increases health burdens and financial costs. Limitations of current smoking cessation therapies indicate the need for improved molecular targets. The main addictive component of tobacco, nicotine, exerts its dependency effects via nicotinic acetylcholine receptors (nAChRs). Activation of the homomeric α7 nAChR reduces nicotine's rewarding properties in conditioned place preference (CPP) test and i.v. self-administration models, but the mechanism underlying these effects is unknown. Recently, the nuclear receptor peroxisome proliferator-activated receptor type-α (PPARα) has been implicated as a downstream signaling target of the α7 nAChR in ventral tegmental area dopamine cells. The present study investigated PPARα as a possible mediator of the effect of α7 nAChR activation in nicotine dependence. Our results demonstrate the PPARα antagonist GW6471 blocks actions of the α7 nAChR agonist PNU282987 on nicotine reward in an unbiased CPP test in male ICR adult mice. These findings suggests that α7 nAChR activation attenuates nicotine CPP in a PPARα-dependent manner. To evaluate PPARα activation in nicotine dependence we used the selective and potent PPARα agonist, WY-14643 and the clinically used PPARα activator, fenofibrate, in nicotine CPP and we observed attenuation of nicotine preference, but fenofibrate was less potent. We also studied PPARα in nicotine dependence by evaluating its activation in nicotine withdrawal. WY-14643 reversed nicotine withdrawal signs whereas fenofibrate had modest efficacy. This suggests that PPARα plays a role in nicotine reward and withdrawal and that further studies are warranted to elucidate its function in mediating the effects of α7 nAChRs in nicotine dependence. Copyright © 2017 Elsevier Ltd. All rights reserved.

In vivo Interactions between α7 Nicotinic Acetylcholine Receptor and Nuclear Peroxisome Proliferator-Activated Receptor-α: Implication for Nicotine Dependence

PubMed Central

Jackson, Asti; Bagdas, Deniz; Muldoon, Pretal P.; Lichtman, Aron H.; Carroll, F. Ivy; Greenwald, Mark; Miles, Michael F.; Damaj, M. Imad

2017-01-01

Chronic tobacco use dramatically increases health burdens and financial costs. Limitations of current smoking cessation therapies indicate the need for improved molecular targets. The main addictive component of tobacco, nicotine, exerts its dependency effects via nicotinic acetylcholine receptors (nAChRs). Activation of the homomeric α7 nAChR reduces nicotine's rewarding properties in conditioned place preference (CPP) test and i.v. self-administration models, but the mechanism underlying these effects is unknown. Recently, the nuclear receptor peroxisome proliferator-activated receptor type-α (PPARα) has been implicated as a downstream signaling target of the α7 nAChR in ventral tegmental area dopamine cells. The present study investigated PPARα as a possible mediator of the effect of α7 nAChR activation in nicotine dependence. Our results demonstrate the PPARα antagonist GW6471 blocks actions of the α7 nAChR agonist PNU282987 on nicotine reward in an unbiased CPP test in male ICR adult mice. These findings suggests that α7 nAChR activation attenuates nicotine CPP in a PPARα-dependent manner. To evaluate PPARα activation in nicotine dependence we used the selective and potent PPARα agonist, WY-14643 and the clinically used PPARα activator, fenofibrate, in nicotine CPP and we observed attenuation of nicotine preference, but fenofibrate was less potent. We also studied PPARα in nicotine dependence by evaluating its activation in nicotine withdrawal. WY-14643 reversed nicotine withdrawal signs whereas fenofibrate had modest efficacy. This suggests that PPARα plays a role in nicotine reward and withdrawal and that further studies are warranted to elucidate its function in mediating the effects of α7 nAChRs in nicotine dependence. PMID:28279662

Spectroscopic classification of supernova SN 2018Z by NUTS (NOT Un-biased Transient Survey)

NASA Astrophysics Data System (ADS)

Kuncarayakti, H.; Mattila, S.; Kotak, R.; Harmanen, J.; Reynolds, T.; Pastorello, A.; Benetti, S.; Stritzinger, M.; Onori, F.; Somero, A.; Kangas, T.; Lundqvist, P.; Taddia, F.; Ergon, M.

2018-01-01

The NOT Unbiased Transient Survey (NUTS; ATel #8992) collaboration reports the spectroscopic classification of supernova SN 2018Z in host galaxy SDSS J231809.76+212553.5 The observations were performed with the 2.56 m Nordic Optical Telescope equipped with ALFOSC (range 350-950 nm; resolution 1.6 nm) on 2018-01-09.9 UT. Survey Name | IAU Name | Discovery (UT) | Discovery mag | Observation (UT) | Redshift | Type | Phase | Notes PS18ao | SN 2018Z | 2018-01-01.2 | 19.96 | 2018-01-09.9 | 0.102 | Ia | post-maximum? | (1) (1) Redshift was derived from the SN and host absorption features.

On the mathematical foundations of mutually unbiased bases

NASA Astrophysics Data System (ADS)

Thas, Koen

2018-02-01

In order to describe a setting to handle Zauner's conjecture on mutually unbiased bases (MUBs) (stating that in C^d, a set of MUBs of the theoretical maximal size d + 1 exists only if d is a prime power), we pose some fundamental questions which naturally arise. Some of these questions have important consequences for the construction theory of (new) sets of maximal MUBs. Partial answers will be provided in particular cases; more specifically, we will analyze MUBs with associated operator groups that have nilpotence class 2, and consider MUBs of height 1. We will also confirm Zauner's conjecture for MUBs with associated finite nilpotent operator groups.

Rasch scaling paranormal belief and experience: structure and semantics of Thalbourne's Australian Sheep-Goat Scale.

PubMed

Lange, Rense; Thalbourne, Michael A

2002-12-01

Research on the relation between demographic variables and paranormal belief remains controversial given the possible semantic distortions introduced by item and test level biases. We illustrate how Rasch scaling can be used to detect such biases and to quantify their effects, using the Australian Sheep-Goal Scale as a substantive example. Based on data from 1.822 respondents, this test was Rasch scalable, reliable, and unbiased at the test level. Consistent with other research in which unbiased measures of paranormal belief were used, extremely weak age and sex effects were found (partial eta2 = .005 and .012, respectively).

Large deviations in the presence of cooperativity and slow dynamics

NASA Astrophysics Data System (ADS)

Whitelam, Stephen

2018-06-01

We study simple models of intermittency, involving switching between two states, within the dynamical large-deviation formalism. Singularities appear in the formalism when switching is cooperative or when its basic time scale diverges. In the first case the unbiased trajectory distribution undergoes a symmetry breaking, leading to a change in shape of the large-deviation rate function for a particular dynamical observable. In the second case the symmetry of the unbiased trajectory distribution remains unbroken. Comparison of these models suggests that singularities of the dynamical large-deviation formalism can signal the dynamical equivalent of an equilibrium phase transition but do not necessarily do so.

Unbiased classification of spatial strategies in the Barnes maze.

PubMed

Illouz, Tomer; Madar, Ravit; Clague, Charlotte; Griffioen, Kathleen J; Louzoun, Yoram; Okun, Eitan

2016-11-01

Spatial learning is one of the most widely studied cognitive domains in neuroscience. The Morris water maze and the Barnes maze are the most commonly used techniques to assess spatial learning and memory in rodents. Despite the fact that these tasks are well-validated paradigms for testing spatial learning abilities, manual categorization of performance into behavioral strategies is subject to individual interpretation, and thus to bias. We have previously described an unbiased machine-learning algorithm to classify spatial strategies in the Morris water maze. Here, we offer a support vector machine-based, automated, Barnes-maze unbiased strategy (BUNS) classification algorithm, as well as a cognitive score scale that can be used for memory acquisition, reversal training and probe trials. The BUNS algorithm can greatly benefit Barnes maze users as it provides a standardized method of strategy classification and cognitive scoring scale, which cannot be derived from typical Barnes maze data analysis. Freely available on the web at http://okunlab.wix.com/okunlab as a MATLAB application. eitan.okun@biu.ac.ilSupplementary information: Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Unbiased Strain-Typing of Arbovirus Directly from Mosquitoes Using Nanopore Sequencing: A Field-forward Biosurveillance Protocol.

PubMed

Russell, Joseph A; Campos, Brittany; Stone, Jennifer; Blosser, Erik M; Burkett-Cadena, Nathan; Jacobs, Jonathan L

2018-04-03

The future of infectious disease surveillance and outbreak response is trending towards smaller hand-held solutions for point-of-need pathogen detection. Here, samples of Culex cedecei mosquitoes collected in Southern Florida, USA were tested for Venezuelan Equine Encephalitis Virus (VEEV), a previously-weaponized arthropod-borne RNA-virus capable of causing acute and fatal encephalitis in animal and human hosts. A single 20-mosquito pool tested positive for VEEV by quantitative reverse transcription polymerase chain reaction (RT-qPCR) on the Biomeme two3. The virus-positive sample was subjected to unbiased metatranscriptome sequencing on the Oxford Nanopore MinION and shown to contain Everglades Virus (EVEV), an alphavirus in the VEEV serocomplex. Our results demonstrate, for the first time, the use of unbiased sequence-based detection and subtyping of a high-consequence biothreat pathogen directly from an environmental sample using field-forward protocols. The development and validation of methods designed for field-based diagnostic metagenomics and pathogen discovery, such as those suitable for use in mobile "pocket laboratories", will address a growing demand for public health teams to carry out their mission where it is most urgent: at the point-of-need.

Using Maximum Entropy to Find Patterns in Genomes

NASA Astrophysics Data System (ADS)

Liu, Sophia; Hockenberry, Adam; Lancichinetti, Andrea; Jewett, Michael; Amaral, Luis

The existence of over- and under-represented sequence motifs in genomes provides evidence of selective evolutionary pressures on biological mechanisms such as transcription, translation, ligand-substrate binding, and host immunity. To accurately identify motifs and other genome-scale patterns of interest, it is essential to be able to generate accurate null models that are appropriate for the sequences under study. There are currently no tools available that allow users to create random coding sequences with specified amino acid composition and GC content. Using the principle of maximum entropy, we developed a method that generates unbiased random sequences with pre-specified amino acid and GC content. Our method is the simplest way to obtain maximally unbiased random sequences that are subject to GC usage and primary amino acid sequence constraints. This approach can also be easily be expanded to create unbiased random sequences that incorporate more complicated constraints such as individual nucleotide usage or even di-nucleotide frequencies. The ability to generate correctly specified null models will allow researchers to accurately identify sequence motifs which will lead to a better understanding of biological processes. National Institute of General Medical Science, Northwestern University Presidential Fellowship, National Science Foundation, David and Lucile Packard Foundation, Camille Dreyfus Teacher Scholar Award.

Smoothed Biasing Forces Yield Unbiased Free Energies with the Extended-System Adaptive Biasing Force Method

PubMed Central

2016-01-01

We report a theoretical description and numerical tests of the extended-system adaptive biasing force method (eABF), together with an unbiased estimator of the free energy surface from eABF dynamics. Whereas the original ABF approach uses its running estimate of the free energy gradient as the adaptive biasing force, eABF is built on the idea that the exact free energy gradient is not necessary for efficient exploration, and that it is still possible to recover the exact free energy separately with an appropriate estimator. eABF does not directly bias the collective coordinates of interest, but rather fictitious variables that are harmonically coupled to them; therefore is does not require second derivative estimates, making it easily applicable to a wider range of problems than ABF. Furthermore, the extended variables present a smoother, coarse-grain-like sampling problem on a mollified free energy surface, leading to faster exploration and convergence. We also introduce CZAR, a simple, unbiased free energy estimator from eABF trajectories. eABF/CZAR converges to the physical free energy surface faster than standard ABF for a wide range of parameters. PMID:27959559

Prioritizing causal disease genes using unbiased genomic features.

PubMed

Deo, Rahul C; Musso, Gabriel; Tasan, Murat; Tang, Paul; Poon, Annie; Yuan, Christiana; Felix, Janine F; Vasan, Ramachandran S; Beroukhim, Rameen; De Marco, Teresa; Kwok, Pui-Yan; MacRae, Calum A; Roth, Frederick P

2014-12-03

Cardiovascular disease (CVD) is the leading cause of death in the developed world. Human genetic studies, including genome-wide sequencing and SNP-array approaches, promise to reveal disease genes and mechanisms representing new therapeutic targets. In practice, however, identification of the actual genes contributing to disease pathogenesis has lagged behind identification of associated loci, thus limiting the clinical benefits. To aid in localizing causal genes, we develop a machine learning approach, Objective Prioritization for Enhanced Novelty (OPEN), which quantitatively prioritizes gene-disease associations based on a diverse group of genomic features. This approach uses only unbiased predictive features and thus is not hampered by a preference towards previously well-characterized genes. We demonstrate success in identifying genetic determinants for CVD-related traits, including cholesterol levels, blood pressure, and conduction system and cardiomyopathy phenotypes. Using OPEN, we prioritize genes, including FLNC, for association with increased left ventricular diameter, which is a defining feature of a prevalent cardiovascular disorder, dilated cardiomyopathy or DCM. Using a zebrafish model, we experimentally validate FLNC and identify a novel FLNC splice-site mutation in a patient with severe DCM. Our approach stands to assist interpretation of large-scale genetic studies without compromising their fundamentally unbiased nature.

An Automatic Method for Generating an Unbiased Intensity Normalizing Factor in Positron Emission Tomography Image Analysis After Stroke.

PubMed

Nie, Binbin; Liang, Shengxiang; Jiang, Xiaofeng; Duan, Shaofeng; Huang, Qi; Zhang, Tianhao; Li, Panlong; Liu, Hua; Shan, Baoci

2018-06-07

Positron emission tomography (PET) imaging of functional metabolism has been widely used to investigate functional recovery and to evaluate therapeutic efficacy after stroke. The voxel intensity of a PET image is the most important indicator of cellular activity, but is affected by other factors such as the basal metabolic ratio of each subject. In order to locate dysfunctional regions accurately, intensity normalization by a scale factor is a prerequisite in the data analysis, for which the global mean value is most widely used. However, this is unsuitable for stroke studies. Alternatively, a specified scale factor calculated from a reference region is also used, comprising neither hyper- nor hypo-metabolic voxels. But there is no such recognized reference region for stroke studies. Therefore, we proposed a totally data-driven automatic method for unbiased scale factor generation. This factor was generated iteratively until the residual deviation of two adjacent scale factors was reduced by < 5%. Moreover, both simulated and real stroke data were used for evaluation, and these suggested that our proposed unbiased scale factor has better sensitivity and accuracy for stroke studies.

Nanoslit cavity plasmonic modes and built-in fields enhance the CW THz radiation in an unbiased antennaless photomixers array.

PubMed

Mohammad-Zamani, Mohammad Javad; Neshat, Mohammad; Moravvej-Farshi, Mohammad Kazem

2016-01-15

A new generation unbiased antennaless CW terahertz (THz) photomixer emitters array made of asymmetric metal-semiconductor-metal (MSM) gratings with a subwavelength pitch, operating in the optical near-field regime, is proposed. We take advantage of size effects in near-field optics and electrostatics to demonstrate the possibility of enhancing the THz power by 4 orders of magnitude, compared to a similar unbiased antennaless array of the same size that operates in the far-field regime. We show that, with the appropriate choice of grating parameters in such THz sources, the first plasmonic resonant cavity mode in the nanoslit between two adjacent MSMs can enhance the optical near-field absorption and, hence, the generation of photocarriers under the slit in the active medium. These photocarriers, on the other hand, are accelerated by the large built-in electric field sustained under the nanoslits by two dissimilar Schottky barriers to create the desired large THz power that is mainly radiated downward. The proposed structure can be tuned in a broadband frequency range of 0.1-3 THz, with output power increasing with frequency.

Probability Theory Plus Noise: Descriptive Estimation and Inferential Judgment.

PubMed

Costello, Fintan; Watts, Paul

2018-01-01

We describe a computational model of two central aspects of people's probabilistic reasoning: descriptive probability estimation and inferential probability judgment. This model assumes that people's reasoning follows standard frequentist probability theory, but it is subject to random noise. This random noise has a regressive effect in descriptive probability estimation, moving probability estimates away from normative probabilities and toward the center of the probability scale. This random noise has an anti-regressive effect in inferential judgement, however. These regressive and anti-regressive effects explain various reliable and systematic biases seen in people's descriptive probability estimation and inferential probability judgment. This model predicts that these contrary effects will tend to cancel out in tasks that involve both descriptive estimation and inferential judgement, leading to unbiased responses in those tasks. We test this model by applying it to one such task, described by Gallistel et al. ). Participants' median responses in this task were unbiased, agreeing with normative probability theory over the full range of responses. Our model captures the pattern of unbiased responses in this task, while simultaneously explaining systematic biases away from normatively correct probabilities seen in other tasks. Copyright © 2018 Cognitive Science Society, Inc.

Comparison of estimators of standard deviation for hydrologic time series

USGS Publications Warehouse

Tasker, Gary D.; Gilroy, Edward J.

1982-01-01

Unbiasing factors as a function of serial correlation, ρ, and sample size, n for the sample standard deviation of a lag one autoregressive model were generated by random number simulation. Monte Carlo experiments were used to compare the performance of several alternative methods for estimating the standard deviation σ of a lag one autoregressive model in terms of bias, root mean square error, probability of underestimation, and expected opportunity design loss. Three methods provided estimates of σ which were much less biased but had greater mean square errors than the usual estimate of σ: s = (1/(n - 1) ∑ (xi −x¯)2)½. The three methods may be briefly characterized as (1) a method using a maximum likelihood estimate of the unbiasing factor, (2) a method using an empirical Bayes estimate of the unbiasing factor, and (3) a robust nonparametric estimate of σ suggested by Quenouille. Because s tends to underestimate σ, its use as an estimate of a model parameter results in a tendency to underdesign. If underdesign losses are considered more serious than overdesign losses, then the choice of one of the less biased methods may be wise.

Reheating-volume measure for random-walk inflation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Winitzki, Sergei; Yukawa Institute of Theoretical Physics, Kyoto University, Kyoto

2008-09-15

The recently proposed 'reheating-volume' (RV) measure promises to solve the long-standing problem of extracting probabilistic predictions from cosmological multiverse scenarios involving eternal inflation. I give a detailed description of the new measure and its applications to generic models of eternal inflation of random-walk type. For those models I derive a general formula for RV-regulated probability distributions that is suitable for numerical computations. I show that the results of the RV cutoff in random-walk type models are always gauge invariant and independent of the initial conditions at the beginning of inflation. In a toy model where equal-time cutoffs lead to themore » 'youngness paradox', the RV cutoff yields unbiased results that are distinct from previously proposed measures.« less

Charge Yield at Low Electric Fields: Considerations for Bipolar Integrated Circuits

NASA Technical Reports Server (NTRS)

Johnston, A. H.; Swimm, R. T.; Thorbourn, D. O.

2013-01-01

A significant reduction in total dose damage is observed when bipolar integrated circuits are irradiated at low temperature. This can be partially explained by the Onsager theory of recombination, which predicts a strong temperature dependence for charge yield under low-field conditions. Reduced damage occurs for biased as well as unbiased devices because the weak fringing field in thick bipolar oxides only affects charge yield near the Si/SiO2 interface, a relatively small fraction of the total oxide thickness. Lowering the temperature of bipolar ICs - either continuously, or for time periods when they are exposed to high radiation levels - provides an additional degree of freedom to improve total dose performance of bipolar circuits, particularly in space applications.

Gender disparities in health care.

PubMed

Kent, Jennifer A; Patel, Vinisha; Varela, Natalie A

2012-01-01

The existence of disparities in delivery of health care has been the subject of increased empirical study in recent years. Some studies have suggested that disparities between men and women exist in the diagnoses and treatment of health conditions, and as a result measures have been taken to identify these differences. This article uses several examples to illustrate health care gender bias in medicine. These examples include surgery, peripheral artery disease, cardiovascular disease, critical care, and cardiovascular risk factors. Additionally, we discuss reasons why these issues still occur, trends in health care that may address these issues, and the need for acknowledgement of the current system's inequities in order to provide unbiased care for women in the future. © 2012 Mount Sinai School of Medicine.

Cemento-osseous dysplasia in an elderly Asian male: a case report.

PubMed

Komabayashi, Takashi; Zhu, Qiang

2011-03-01

Cemento-osseous dysplasia is a disorder typically found in middle-aged black women. However, the present report describes a case in a 61-year-old Vietnamese male. Without proper pulp testing and diagnosis, the radiographic presentation can easily be misdiagnosed as periapical periodontitis. On the basis of pulp vitality, lack of clinical symptoms and radiographic features, the diagnosis in this case was periapical cemento-osseous dysplasia at the mixed stage, which generally requires no treatment. At the 18-month follow-up, the patient was still asymptomatic and none of the clinical signs had changed. This case highlights the importance of careful clinical examination, including a pulp vitality test, and of having an unbiased view of age, gender, and ethnicity when diagnosing this condition.

Eigenstate Thermalization for Degenerate Observables

NASA Astrophysics Data System (ADS)

Anza, Fabio; Gogolin, Christian; Huber, Marcus

2018-04-01

Under unitary time evolution, expectation values of physically reasonable observables often evolve towards the predictions of equilibrium statistical mechanics. The eigenstate thermalization hypothesis (ETH) states that this is also true already for individual energy eigenstates. Here we aim at elucidating the emergence of the ETH for observables that can realistically be measured due to their high degeneracy, such as local, extensive, or macroscopic observables. We bisect this problem into two parts, a condition on the relative overlaps and one on the relative phases between the eigenbases of the observable and Hamiltonian. We show that the relative overlaps are unbiased for highly degenerate observables and demonstrate that unless relative phases conspire to cumulative effects, this makes such observables verify the ETH. Through this we elucidate potential pathways towards proofs of thermalization.

Detection of human disease conditions by single-cell morpho-rheological phenotyping of blood.

PubMed

Toepfner, Nicole; Herold, Christoph; Otto, Oliver; Rosendahl, Philipp; Jacobi, Angela; Kräter, Martin; Stächele, Julia; Menschner, Leonhard; Herbig, Maik; Ciuffreda, Laura; Ranford-Cartwright, Lisa; Grzybek, Michal; Coskun, Ünal; Reithuber, Elisabeth; Garriss, Geneviève; Mellroth, Peter; Henriques-Normark, Birgitta; Tregay, Nicola; Suttorp, Meinolf; Bornhäuser, Martin; Chilvers, Edwin R; Berner, Reinhard; Guck, Jochen

2018-01-13

Blood is arguably the most important bodily fluid and its analysis provides crucial health status information. A first routine measure to narrow down diagnosis in clinical practice is the differential blood count, determining the frequency of all major blood cells. What is lacking to advance initial blood diagnostics is an unbiased and quick functional assessment of blood that can narrow down the diagnosis and generate specific hypotheses. To address this need, we introduce the continuous, cell-by-cell morpho-rheological (MORE) analysis of diluted whole blood, without labeling, enrichment or separation, at rates of 1000 cells/sec. In a drop of blood we can identify all major blood cells and characterize their pathological changes in several disease conditions in vitro and in patient samples. This approach takes previous results of mechanical studies on specifically isolated blood cells to the level of application directly in blood and adds a functional dimension to conventional blood analysis. © 2018, Toepfner et al.

Detection of human disease conditions by single-cell morpho-rheological phenotyping of blood

PubMed Central

Toepfner, Nicole; Herold, Christoph; Otto, Oliver; Rosendahl, Philipp; Jacobi, Angela; Kräter, Martin; Stächele, Julia; Menschner, Leonhard; Herbig, Maik; Ciuffreda, Laura; Ranford-Cartwright, Lisa; Grzybek, Michal; Coskun, Ünal; Reithuber, Elisabeth; Garriss, Geneviève; Mellroth, Peter; Henriques-Normark, Birgitta; Tregay, Nicola; Suttorp, Meinolf; Bornhäuser, Martin; Chilvers, Edwin R; Berner, Reinhard

2018-01-01

Blood is arguably the most important bodily fluid and its analysis provides crucial health status information. A first routine measure to narrow down diagnosis in clinical practice is the differential blood count, determining the frequency of all major blood cells. What is lacking to advance initial blood diagnostics is an unbiased and quick functional assessment of blood that can narrow down the diagnosis and generate specific hypotheses. To address this need, we introduce the continuous, cell-by-cell morpho-rheological (MORE) analysis of diluted whole blood, without labeling, enrichment or separation, at rates of 1000 cells/sec. In a drop of blood we can identify all major blood cells and characterize their pathological changes in several disease conditions in vitro and in patient samples. This approach takes previous results of mechanical studies on specifically isolated blood cells to the level of application directly in blood and adds a functional dimension to conventional blood analysis. PMID:29331015

Unbiased and unnoticed verbal conditioning: the double agent robot procedure1

PubMed Central

Rosenfeld, Howard M.; Baer, Donald M.

1970-01-01

Subjects who were told they were “experimenters” attempted to reinforce fluent speech in a supposed subject with whom they spoke via intercom. The supposed subject was to say nouns, one at a time, on request by the “experimenter”, who reinforced fluent pronunciation with points. Actually, the “experimenter” was talking to a multi-track tape recording, one track of which contained fluently spoken nouns, the other track containing disfluently spoken nouns. If the “experimenter's” request for the next noun was in a specified form a word from the fluent track was played to him as reinforcement; requests in any other form produced the word from the disfluent track. Repeated conditioning of specific forms of requests was accomplished with two subject-“experimenters,” who were unable to describe changes in their own behavior, or the contingencies applied. This technique improved upon an earlier method that had yielded similar results, but was less thoroughly controlled against possible human bias. PMID:16811461

Doubly robust estimation of generalized partial linear models for longitudinal data with dropouts.

PubMed

Lin, Huiming; Fu, Bo; Qin, Guoyou; Zhu, Zhongyi

2017-12-01

We develop a doubly robust estimation of generalized partial linear models for longitudinal data with dropouts. Our method extends the highly efficient aggregate unbiased estimating function approach proposed in Qu et al. (2010) to a doubly robust one in the sense that under missing at random (MAR), our estimator is consistent when either the linear conditional mean condition is satisfied or a model for the dropout process is correctly specified. We begin with a generalized linear model for the marginal mean, and then move forward to a generalized partial linear model, allowing for nonparametric covariate effect by using the regression spline smoothing approximation. We establish the asymptotic theory for the proposed method and use simulation studies to compare its finite sample performance with that of Qu's method, the complete-case generalized estimating equation (GEE) and the inverse-probability weighted GEE. The proposed method is finally illustrated using data from a longitudinal cohort study. © 2017, The International Biometric Society.

The case test-negative design for studies of the effectiveness of influenza vaccine in inpatient settings.

PubMed

Foppa, Ivo M; Ferdinands, Jill M; Chaves, Sandra S; Haber, Michael J; Reynolds, Sue B; Flannery, Brendan; Fry, Alicia M

2016-12-01

The test-negative design (TND) to evaluate influenza vaccine effectiveness is based on patients seeking care for acute respiratory infection, with those who test positive for influenza as cases and the test-negatives serving as controls. This design has not been validated for the inpatient setting where selection bias might be different from an outpatient setting. We derived mathematical expressions for vaccine effectiveness (VE) against laboratory-confirmed influenza hospitalizations and used numerical simulations to verify theoretical results exploring expected biases under various scenarios. We explored meaningful interpretations of VE estimates from inpatient TND studies. VE estimates from inpatient TND studies capture the vaccine-mediated protection of the source population against laboratory-confirmed influenza hospitalizations. If vaccination does not modify disease severity, these estimates are equivalent to VE against influenza virus infection. If chronic cardiopulmonary individuals are enrolled because of non-infectious exacerbation, biased VE estimates (too high) will result. If chronic cardiopulmonary disease status is adjusted for accurately, the VE estimates will be unbiased. If chronic cardiopulmonary illness cannot be adequately be characterized, excluding these individuals may provide unbiased VE estimates. The inpatient TND offers logistic advantages and can provide valid estimates of influenza VE. If highly vaccinated patients with respiratory exacerbation of chronic cardiopulmonary conditions are eligible for study inclusion, biased VE estimates will result unless this group is well characterized and the analysis can adequately adjust for it. Otherwise, such groups of subjects should be excluded from the analysis. © The Author 2016. Published by Oxford University Press on behalf of the International Epidemiological Association.

Measuring reward with the conditioned place preference (CPP) paradigm: update of the last decade.

PubMed

Tzschentke, Thomas M

2007-09-01

Conditioned place preference (CPP) continues to be one of the most popular models to study the motivational effects of drugs and non-drug treatments in experimental animals. This is obvious from a steady year-to-year increase in the number of publications reporting the use this model. Since the compilation of the preceding review in 1998, more than 1000 new studies using place conditioning have been published, and the aim of the present review is to provide an overview of these recent publications. There are a number of trends and developments that are obvious in the literature of the last decade. First, as more and more knockout and transgenic animals become available, place conditioning is increasingly used to assess the motivational effects of drugs or non-drug rewards in genetically modified animals. Second, there is a still small but growing literature on the use of place conditioning to study the motivational aspects of pain, a field of pre-clinical research that has so far received little attention, because of the lack of appropriate animal models. Third, place conditioning continues to be widely used to study tolerance and sensitization to the rewarding effects of drugs induced by pre-treatment regimens. Fourth, extinction/reinstatement procedures in place conditioning are becoming increasingly popular. This interesting approach is thought to model certain aspects of relapse to addictive behavior and has previously almost exclusively been studied in drug self-administration paradigms. It has now also become established in the place conditioning literature and provides an additional and technically easy approach to this important phenomenon. The enormous number of studies to be covered in this review prevented in-depth discussion of many methodological, pharmacological or neurobiological aspects; to a large extent, the presentation of data had to be limited to a short and condensed summary of the most relevant findings.

Solution to the mean king's problem with mutually unbiased bases for arbitrary levels

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kimura, Gen; Tanaka, Hajime; Ozawa, Masanao

2006-05-15

The mean king's problem with mutually unbiased bases is reconsidered for arbitrary d-level systems. Hayashi et al. [Phys. Rev. A 71, 052331 (2005)] related the problem to the existence of a maximal set of d-1 mutually orthogonal Latin squares, in their restricted setting that allows only measurements of projection-valued measures. However, we then cannot find a solution to the problem when, e.g., d=6 or d=10. In contrast to their result, we show that the king's problem always has a solution for arbitrary levels if we also allow positive operator-valued measures. In constructing the solution, we use orthogonal arrays in combinatorialmore » design theory.« less

Human systems immunology: hypothesis-based modeling and unbiased data-driven approaches.

PubMed

Arazi, Arnon; Pendergraft, William F; Ribeiro, Ruy M; Perelson, Alan S; Hacohen, Nir

2013-10-31

Systems immunology is an emerging paradigm that aims at a more systematic and quantitative understanding of the immune system. Two major approaches have been utilized to date in this field: unbiased data-driven modeling to comprehensively identify molecular and cellular components of a system and their interactions; and hypothesis-based quantitative modeling to understand the operating principles of a system by extracting a minimal set of variables and rules underlying them. In this review, we describe applications of the two approaches to the study of viral infections and autoimmune diseases in humans, and discuss possible ways by which these two approaches can synergize when applied to human immunology. Copyright © 2012 Elsevier Ltd. All rights reserved.

A cross-correlation-based estimate of the galaxy luminosity function

NASA Astrophysics Data System (ADS)

van Daalen, Marcel P.; White, Martin

2018-06-01

We extend existing methods for using cross-correlations to derive redshift distributions for photometric galaxies, without using photometric redshifts. The model presented in this paper simultaneously yields highly accurate and unbiased redshift distributions and, for the first time, redshift-dependent luminosity functions, using only clustering information and the apparent magnitudes of the galaxies as input. In contrast to many existing techniques for recovering unbiased redshift distributions, the output of our method is not degenerate with the galaxy bias b(z), which is achieved by modelling the shape of the luminosity bias. We successfully apply our method to a mock galaxy survey and discuss improvements to be made before applying our model to real data.

Unbiased Sampling of Globular Lattice Proteins in Three Dimensions

NASA Astrophysics Data System (ADS)

Jacobsen, Jesper Lykke

2008-03-01

We present a Monte Carlo method that allows efficient and unbiased sampling of Hamiltonian walks on a cubic lattice. Such walks are self-avoiding and visit each lattice site exactly once. They are often used as simple models of globular proteins, upon adding suitable local interactions. Our algorithm can easily be equipped with such interactions, but we study here mainly the flexible homopolymer case where each conformation is generated with uniform probability. We argue that the algorithm is ergodic and has dynamical exponent z=0. We then use it to study polymers of size up to 643=262144 monomers. Results are presented for the effective interaction between end points, and the interaction with the boundaries of the system.

Attenuation of Cocaine-Induced Conditioned Place Preference and Motor Activity via Cannabinoid CB2 Receptor Agonism and CB1 Receptor Antagonism in Rats

PubMed Central

Delis, Foteini; Polissidis, Alexia; Poulia, Nafsika; Justinova, Zuzana; Nomikos, George G.; Goldberg, Steven R.

2017-01-01

Abstract Background: Studies have shown the involvement of cannabinoid (CB) receptors in the behavioral and neurobiological effects of psychostimulants. Most of these studies have focused on the role of CB1 receptors in the psychostimulant effects of cocaine, while very few have investigated the respective role of CB2 receptors. Further studies are warranted to elucidate the extent of CB receptor involvement in the expression of cocaine-induced effects. Methods: The role of CB1 and CB2 receptors in the rewarding and motor properties of cocaine was assessed in conditioned place preference, conditioned motor activity, and open field activity in rats. Results: The CB1 receptor antagonist rimonabant (3 mg/kg) decreased the acquisition and the expression of conditioned place preference induced by cocaine (20 mg/kg). Rimonabant inhibited cocaine-elicited conditioned motor activity when administered during the expression of cocaine-induced conditioned place preference. Rimonabant decreased ambulatory and vertical activity induced by cocaine. The CB2 receptor agonist JWH-133 (10 mg/kg) decreased the acquisition and the expression of cocaine-induced conditioned place preference. JWH-133 inhibited cocaine-elicited conditioned motor activity when administered during the acquisition and the expression of cocaine-induced conditioned place preference. JWH-133 decreased ambulatory activity and abolished vertical activity induced by cocaine. The effects of JWH-133 on cocaine conditioned and stimulated responses were abolished when the CB2 receptor antagonist/inverse agonist AM630 (5 mg/kg) was preadministered. Conclusions: Cannabinoid CB1 and CB2 receptors modulate cocaine-induced rewarding behavior and appear to have opposite roles in the regulation of cocaine’s reinforcing and psychomotor effects. PMID:27994006

A Rapid and Efficient Method for Evaluation of Suspect Testimony: Palynological Scanning.

PubMed

Wiltshire, Patricia E J; Hawksworth, David L; Edwards, Kevin J

2015-11-01

A rapid method for evaluating suspect testimony is valuable at any stage in an inquiry and can result in a change of direction in an investigation. Rape cases, in particular, can present problems where a defendant renders DNA analysis redundant by claiming that the claimant consented to have sexual relations. Forensic palynology is valuable in confirming or eliminating locations as being crime scenes, thus checking the testimony of both parties. In contrast to some forensic disciplines, forensic palynology can provide critical information without time-consuming full analysis. Two cases are described where the palynological assemblages from comparator samples of pertinent places were compared with those obtained from clothing of claimants and defendants. The results of rapid microscopical scanning of relevant preparations led to early confessions, thus obviating the need for costly analyses and protracted court proceedings. A third case demonstrates the unbiased nature of this technique where a man, although innocent of any offense, lied about having visited the crime scene for fear of prosecution. This highlights the need for sensitive policing in claims of rape. © 2015 American Academy of Forensic Sciences.

An siRNA-based functional genomics screen for the identification of regulators of ciliogenesis and ciliopathy genes

PubMed Central

Racher, Hilary; Phelps, Ian G.; Toedt, Grischa; Kennedy, Julie; Wunderlich, Kirsten A.; Sorusch, Nasrin; Abdelhamed, Zakia A.; Natarajan, Subaashini; Herridge, Warren; van Reeuwijk, Jeroen; Horn, Nicola; Boldt, Karsten; Parry, David A.; Letteboer, Stef J.F.; Roosing, Susanne; Adams, Matthew; Bell, Sandra M.; Bond, Jacquelyn; Higgins, Julie; Morrison, Ewan E.; Tomlinson, Darren C.; Slaats, Gisela G.; van Dam, Teunis J. P.; Huang, Lijia; Kessler, Kristin; Giessl, Andreas; Logan, Clare V.; Boyle, Evan A.; Shendure, Jay; Anazi, Shamsa; Aldahmesh, Mohammed; Al Hazzaa, Selwa; Hegele, Robert A.; Ober, Carole; Frosk, Patrick; Mhanni, Aizeddin A.; Chodirker, Bernard N.; Chudley, Albert E.; Lamont, Ryan; Bernier, Francois P.; Beaulieu, Chandree L.; Gordon, Paul; Pon, Richard T.; Donahue, Clem; Barkovich, A. James; Wolf, Louis; Toomes, Carmel; Thiel, Christian T.; Boycott, Kym M.; McKibbin, Martin; Inglehearn, Chris F.; Stewart, Fiona; Omran, Heymut; Huynen, Martijn A.; Sergouniotis, Panagiotis I.; Alkuraya, Fowzan S.; Parboosingh, Jillian S.; Innes, A Micheil; Willoughby, Colin E.; Giles, Rachel H.; Webster, Andrew R.; Ueffing, Marius; Blacque, Oliver; Gleeson, Joseph G.; Wolfrum, Uwe; Beales, Philip L.; Gibson, Toby

2015-01-01

Defects in primary cilium biogenesis underlie the ciliopathies, a growing group of genetic disorders. We describe a whole genome siRNA-based reverse genetics screen for defects in biogenesis and/or maintenance of the primary cilium, obtaining a global resource. We identify 112 candidate ciliogenesis and ciliopathy genes, including 44 components of the ubiquitin-proteasome system, 12 G-protein-coupled receptors, and three pre-mRNA processing factors (PRPF6, PRPF8 and PRPF31) mutated in autosomal dominant retinitis pigmentosa. The PRPFs localise to the connecting cilium, and PRPF8- and PRPF31-mutated cells have ciliary defects. Combining the screen with exome sequencing data identified recessive mutations in PIBF1/CEP90 and C21orf2/LRRC76 as causes of the ciliopathies Joubert and Jeune syndromes. Biochemical approaches place C21orf2 within key ciliopathy-associated protein modules, offering an explanation for the skeletal and retinal involvement observed in individuals with C21orf2-variants. Our global, unbiased approaches provide insights into ciliogenesis complexity and identify roles for unanticipated pathways in human genetic disease. PMID:26167768

Software engineering the mixed model for genome-wide association studies on large samples.

PubMed

Zhang, Zhiwu; Buckler, Edward S; Casstevens, Terry M; Bradbury, Peter J

2009-11-01

Mixed models improve the ability to detect phenotype-genotype associations in the presence of population stratification and multiple levels of relatedness in genome-wide association studies (GWAS), but for large data sets the resource consumption becomes impractical. At the same time, the sample size and number of markers used for GWAS is increasing dramatically, resulting in greater statistical power to detect those associations. The use of mixed models with increasingly large data sets depends on the availability of software for analyzing those models. While multiple software packages implement the mixed model method, no single package provides the best combination of fast computation, ability to handle large samples, flexible modeling and ease of use. Key elements of association analysis with mixed models are reviewed, including modeling phenotype-genotype associations using mixed models, population stratification, kinship and its estimation, variance component estimation, use of best linear unbiased predictors or residuals in place of raw phenotype, improving efficiency and software-user interaction. The available software packages are evaluated, and suggestions made for future software development.

Evaluation of unconfined-aquifer parameters from pumping test data by nonlinear least squares

NASA Astrophysics Data System (ADS)

Heidari, Manoutchehr; Wench, Allen

1997-05-01

Nonlinear least squares (NLS) with automatic differentiation was used to estimate aquifer parameters from drawdown data obtained from published pumping tests conducted in homogeneous, water-table aquifers. The method is based on a technique that seeks to minimize the squares of residuals between observed and calculated drawdown subject to bounds that are placed on the parameter of interest. The analytical model developed by Neuman for flow to a partially penetrating well of infinitesimal diameter situated in an infinite, homogeneous and anisotropic aquifer was used to obtain calculated drawdown. NLS was first applied to synthetic drawdown data from a hypothetical but realistic aquifer to demonstrate that the relevant hydraulic parameters (storativity, specific yield, and horizontal and vertical hydraulic conductivity) can be evaluated accurately. Next the method was used to estimate the parameters at three field sites with widely varying hydraulic properties. NLS produced unbiased estimates of the aquifer parameters that are close to the estimates obtained with the same data using a visual curve-matching approach. Small differences in the estimates are a consequence of subjective interpretation introduced in the visual approach.

Evaluation of unconfined-aquifer parameters from pumping test data by nonlinear least squares

USGS Publications Warehouse

Heidari, M.; Moench, A.

1997-01-01

Nonlinear least squares (NLS) with automatic differentiation was used to estimate aquifer parameters from drawdown data obtained from published pumping tests conducted in homogeneous, water-table aquifers. The method is based on a technique that seeks to minimize the squares of residuals between observed and calculated drawdown subject to bounds that are placed on the parameter of interest. The analytical model developed by Neuman for flow to a partially penetrating well of infinitesimal diameter situated in an infinite, homogeneous and anisotropic aquifer was used to obtain calculated drawdown. NLS was first applied to synthetic drawdown data from a hypothetical but realistic aquifer to demonstrate that the relevant hydraulic parameters (storativity, specific yield, and horizontal and vertical hydraulic conductivity) can be evaluated accurately. Next the method was used to estimate the parameters at three field sites with widely varying hydraulic properties. NLS produced unbiased estimates of the aquifer parameters that are close to the estimates obtained with the same data using a visual curve-matching approach. Small differences in the estimates are a consequence of subjective interpretation introduced in the visual approach.

Unbiased clustering estimation in the presence of missing observations

NASA Astrophysics Data System (ADS)

Bianchi, Davide; Percival, Will J.

2017-11-01

In order to be efficient, spectroscopic galaxy redshift surveys do not obtain redshifts for all galaxies in the population targeted. The missing galaxies are often clustered, commonly leading to a lower proportion of successful observations in dense regions. One example is the close-pair issue for SDSS spectroscopic galaxy surveys, which have a deficit of pairs of observed galaxies with angular separation closer than the hardware limit on placing neighbouring fibres. Spatially clustered missing observations will exist in the next generations of surveys. Various schemes have previously been suggested to mitigate these effects, but none works for all situations. We argue that the solution is to link the missing galaxies to those observed with statistically equivalent clustering properties, and that the best way to do this is to rerun the targeting algorithm, varying the angular position of the observations. Provided that every pair has a non-zero probability of being observed in one realization of the algorithm, then a pair-upweighting scheme linking targets to successful observations, can correct these issues. We present such a scheme, and demonstrate its validity using realizations of an idealized simple survey strategy.

Constraints on Planetary Companions in the Magnification A=256 Microlensing Event OGLE-2003-BLG-423

NASA Astrophysics Data System (ADS)

Yoo, Jaiyul; DePoy, D. L.; Gal-Yam, A.; Gaudi, B. S.; Gould, A.; Han, C.; Lipkin, Y.; Maoz, D.; Ofek, E. O.; Park, B.-G.; Pogge, R. W.; Mu Fun Collaboration; Szymański, M. K.; Udalski, A.; Szewczyk, O.; Kubiak, M.; Żebruń, K.; Pietrzyński, G.; Soszyński, I.; Wyrzykowski, Ł.; OGLE Collaboration

2004-12-01

We develop a new method of modeling microlensing events based on a Monte Carlo simulation that incorporates both a Galactic model and the constraints imposed by the observed characteristics of the event. The method provides an unbiased way to analyze the event, especially when parameters are poorly constrained by the observed light curve. We apply this method to search for planetary companions of the lens in OGLE-2003-BLG-423, whose maximum magnification Amax=256+/-43 (or Amax=400+/-115 from the light-curve data alone) is the highest among single-lens events ever recorded. The method permits us for the first time to place constraints directly in the planet mass-projected physical separation plane rather than in the mass ratio-Einstein radius plane as was done previously. For example, Jovian-mass companions of main-sequence stars at 2.5 AU are excluded with 80% efficiency. Based in part on observations obtained with the 1.3 m Warsaw Telescope at the Las Campanas Observatory of the Carnegie Institution of Washington.

15 CFR 285.1 - Purpose.

Code of Federal Regulations, 2010 CFR

2010-01-01

... AND TECHNOLOGY, DEPARTMENT OF COMMERCE ACCREDITATION AND ASSESSMENT PROGRAMS NATIONAL VOLUNTARY... as an unbiased third party to accredit both testing and calibration laboratories. Supplementary...

15 CFR 285.1 - Purpose.

Code of Federal Regulations, 2014 CFR

2014-01-01

... AND TECHNOLOGY, DEPARTMENT OF COMMERCE ACCREDITATION AND ASSESSMENT PROGRAMS NATIONAL VOLUNTARY... as an unbiased third party to accredit both testing and calibration laboratories. Supplementary...

15 CFR 285.1 - Purpose.

Code of Federal Regulations, 2013 CFR

2013-01-01

... AND TECHNOLOGY, DEPARTMENT OF COMMERCE ACCREDITATION AND ASSESSMENT PROGRAMS NATIONAL VOLUNTARY... as an unbiased third party to accredit both testing and calibration laboratories. Supplementary...

15 CFR 285.1 - Purpose.

Code of Federal Regulations, 2011 CFR

2011-01-01

... AND TECHNOLOGY, DEPARTMENT OF COMMERCE ACCREDITATION AND ASSESSMENT PROGRAMS NATIONAL VOLUNTARY... as an unbiased third party to accredit both testing and calibration laboratories. Supplementary...

15 CFR 285.1 - Purpose.

Code of Federal Regulations, 2012 CFR

2012-01-01

... AND TECHNOLOGY, DEPARTMENT OF COMMERCE ACCREDITATION AND ASSESSMENT PROGRAMS NATIONAL VOLUNTARY... as an unbiased third party to accredit both testing and calibration laboratories. Supplementary...

Unbiased and targeted mass spectrometry for the HDL proteome.

PubMed

Singh, Sasha A; Aikawa, Masanori

2017-02-01

Mass spectrometry is an ever evolving technology that is equipped with a variety of tools for protein research. Some lipoprotein studies, especially those pertaining to HDL biology, have been exploiting the versatility of mass spectrometry to understand HDL function through its proteome. Despite the role of mass spectrometry in advancing research as a whole, however, the technology remains obscure to those without hands on experience, but still wishing to understand it. In this review, we walk the reader through the coevolution of common mass spectrometry workflows and HDL research, starting from the basic unbiased mass spectrometry methods used to profile the HDL proteome to the most recent targeted methods that have enabled an unprecedented view of HDL metabolism. Unbiased global proteomics have demonstrated that the HDL proteome is organized into subgroups across the HDL size fractions providing further evidence that HDL functional heterogeneity is in part governed by its varying protein constituents. Parallel reaction monitoring, a novel targeted mass spectrometry method, was used to monitor the metabolism of HDL apolipoproteins in humans and revealed that apolipoproteins contained within the same HDL size fraction exhibit diverse metabolic properties. Mass spectrometry provides a variety of tools and strategies to facilitate understanding, through its proteins, the complex biology of HDL.

Sampling for Patient Exit Interviews: Assessment of Methods Using Mathematical Derivation and Computer Simulations.

PubMed

Geldsetzer, Pascal; Fink, Günther; Vaikath, Maria; Bärnighausen, Till

2018-02-01

(1) To evaluate the operational efficiency of various sampling methods for patient exit interviews; (2) to discuss under what circumstances each method yields an unbiased sample; and (3) to propose a new, operationally efficient, and unbiased sampling method. Literature review, mathematical derivation, and Monte Carlo simulations. Our simulations show that in patient exit interviews it is most operationally efficient if the interviewer, after completing an interview, selects the next patient exiting the clinical consultation. We demonstrate mathematically that this method yields a biased sample: patients who spend a longer time with the clinician are overrepresented. This bias can be removed by selecting the next patient who enters, rather than exits, the consultation room. We show that this sampling method is operationally more efficient than alternative methods (systematic and simple random sampling) in most primary health care settings. Under the assumption that the order in which patients enter the consultation room is unrelated to the length of time spent with the clinician and the interviewer, selecting the next patient entering the consultation room tends to be the operationally most efficient unbiased sampling method for patient exit interviews. © 2016 The Authors. Health Services Research published by Wiley Periodicals, Inc. on behalf of Health Research and Educational Trust.

Transfer of location-specific control to untrained locations.

PubMed

Weidler, Blaire J; Bugg, Julie M

2016-11-01

Recent research highlights a seemingly flexible and automatic form of cognitive control that is triggered by potent contextual cues, as exemplified by the location-specific proportion congruence effect--reduced compatibility effects in locations associated with a high as compared to low likelihood of conflict. We investigated just how flexible location-specific control is by examining whether novel locations effectively cue control for congruency-unbiased stimuli. In two experiments, biased (mostly compatible or mostly incompatible) training stimuli appeared in distinct locations. During a final block, unbiased (50% compatible) stimuli appeared in novel untrained locations spatially linked to biased locations. The flanker compatibly effect was reduced for unbiased stimuli in novel locations linked to a mostly incompatible compared to a mostly compatible location, indicating transfer. Transfer was observed when stimuli appeared along a linear function (Experiment 1) or in rings of a bullseye (Experiment 2). The novel transfer effects imply that location-specific control is more flexible than previously reported and further counter the complex stimulus-response learning account of location-specific proportion congruence effects. We propose that the representation and retrieval of control settings in untrained locations may depend on environmental support and the presentation of stimuli in novel locations that fall within the same categories of space as trained locations.

Unbiased compound screening with a reporter gene assay highlights the role of p13 in the cardiac cellular stress response.

PubMed

Inoue, Naoki; Hirouchi, Taisei; Kasai, Atsushi; Higashi, Shintaro; Hiraki, Natsumi; Tanaka, Shota; Nakazawa, Takanobu; Nunomura, Kazuto; Lin, Bangzhong; Omori, Akiko; Hayata-Takano, Atsuko; Kim, Yoon-Jeong; Doi, Takefumi; Baba, Akemichi; Hashimoto, Hitoshi; Shintani, Norihito

2018-01-08

We recently showed that a 13-kDa protein (p13), the homolog protein of formation of mitochondrial complex V assembly factor 1 in yeast, acts as a potential protective factor in pancreatic islets under diabetes. Here, we aimed to identify known compounds regulating p13 mRNA expression to obtain therapeutic insight into the cellular stress response. A luciferase reporter system was developed using the putative promoter region of the human p13 gene. Overexpression of peroxisome proliferator-activated receptor gamma coactivator 1α, a master player regulating mitochondrial metabolism, increased both reporter activity and p13 expression. Following unbiased screening with 2320 known compounds in HeLa cells, 12 pharmacological agents (including 8 cardiotonics and 2 anthracyclines) that elicited >2-fold changes in p13 mRNA expression were identified. Among them, four cardiac glycosides decreased p13 expression and concomitantly elevated cellular oxidative stress. Additional database analyses showed highest p13 expression in heart, with typically decreased expression in cardiac disease. Accordingly, our results illustrate the usefulness of unbiased compound screening as a method for identifying novel functional roles of unfamiliar genes. Our findings also highlight the importance of p13 in the cellular stress response in heart. Copyright © 2017. Published by Elsevier Inc.

State estimation of spatio-temporal phenomena

NASA Astrophysics Data System (ADS)

Yu, Dan

This dissertation addresses the state estimation problem of spatio-temporal phenomena which can be modeled by partial differential equations (PDEs), such as pollutant dispersion in the atmosphere. After discretizing the PDE, the dynamical system has a large number of degrees of freedom (DOF). State estimation using Kalman Filter (KF) is computationally intractable, and hence, a reduced order model (ROM) needs to be constructed first. Moreover, the nonlinear terms, external disturbances or unknown boundary conditions can be modeled as unknown inputs, which leads to an unknown input filtering problem. Furthermore, the performance of KF could be improved by placing sensors at feasible locations. Therefore, the sensor scheduling problem to place multiple mobile sensors is of interest. The first part of the dissertation focuses on model reduction for large scale systems with a large number of inputs/outputs. A commonly used model reduction algorithm, the balanced proper orthogonal decomposition (BPOD) algorithm, is not computationally tractable for large systems with a large number of inputs/outputs. Inspired by the BPOD and randomized algorithms, we propose a randomized proper orthogonal decomposition (RPOD) algorithm and a computationally optimal RPOD (RPOD*) algorithm, which construct an ROM to capture the input-output behaviour of the full order model, while reducing the computational cost of BPOD by orders of magnitude. It is demonstrated that the proposed RPOD* algorithm could construct the ROM in real-time, and the performance of the proposed algorithms on different advection-diffusion equations. Next, we consider the state estimation problem of linear discrete-time systems with unknown inputs which can be treated as a wide-sense stationary process with rational power spectral density, while no other prior information needs to be known. We propose an autoregressive (AR) model based unknown input realization technique which allows us to recover the input statistics from the output data by solving an appropriate least squares problem, then fit an AR model to the recovered input statistics and construct an innovations model of the unknown inputs using the eigensystem realization algorithm. The proposed algorithm outperforms the augmented two-stage Kalman Filter (ASKF) and the unbiased minimum-variance (UMV) algorithm are shown in several examples. Finally, we propose a framework to place multiple mobile sensors to optimize the long-term performance of KF in the estimation of the state of a PDE. The major challenges are that placing multiple sensors is an NP-hard problem, and the optimization problem is non-convex in general. In this dissertation, first, we construct an ROM using RPOD* algorithm, and then reduce the feasible sensor locations into a subset using the ROM. The Information Space Receding Horizon Control (I-RHC) approach and a modified Monte Carlo Tree Search (MCTS) approach are applied to solve the sensor scheduling problem using the subset. Various applications have been provided to demonstrate the performance of the proposed approach.

Key results of battery performance and life tests at Argonne National Laboratory

NASA Astrophysics Data System (ADS)

Deluca, W. H.; Gillie, K. R.; Kulaga, J. E.; Smaga, J. A.; Tummillo, A. F.; Webster, C. E.

1991-12-01

Advanced battery technology evaluations are performed under simulated electric vehicle operating conditions at Argonne National Laboratory's & Diagnostic Laboratory (ADL). The ADL provide a common basis for both performance characterization and life evaluation with unbiased application of tests and analyses. This paper summarizes the performance characterizations and life evaluations conducted in 1991 on twelve single cells and eight 3- to 360-cell modules that encompass six battery technologies (Na/S, Li/MS, Ni/MH, Zn/Br, Ni/Fe, and Pb-Acid). These evaluations were performed for the Department of Energy, Office of Transportation Technologies, Electric and Hybrid Propulsion Division. The results measure progress in battery R & D programs, compare battery technologies, and provide basic data for modeling and continuing R & D to battery users, developers, and program managers.

Criteria for the use of regression analysis for remote sensing of sediment and pollutants

NASA Technical Reports Server (NTRS)

Whitlock, C. H.; Kuo, C. Y.; Lecroy, S. R.

1982-01-01

An examination of limitations, requirements, and precision of the linear multiple-regression technique for quantification of marine environmental parameters is conducted. Both environmental and optical physics conditions have been defined for which an exact solution to the signal response equations is of the same form as the multiple regression equation. Various statistical parameters are examined to define a criteria for selection of an unbiased fit when upwelled radiance values contain error and are correlated with each other. Field experimental data are examined to define data smoothing requirements in order to satisfy the criteria of Daniel and Wood (1971). Recommendations are made concerning improved selection of ground-truth locations to maximize variance and to minimize physical errors associated with the remote sensing experiment.

Evaluation of low wind modeling approaches for two tall-stack databases.

PubMed

Paine, Robert; Samani, Olga; Kaplan, Mary; Knipping, Eladio; Kumar, Naresh

2015-11-01

The performance of the AERMOD air dispersion model under low wind speed conditions, especially for applications with only one level of meteorological data and no direct turbulence measurements or vertical temperature gradient observations, is the focus of this study. The analysis documented in this paper addresses evaluations for low wind conditions involving tall stack releases for which multiple years of concurrent emissions, meteorological data, and monitoring data are available. AERMOD was tested on two field-study databases involving several SO2 monitors and hourly emissions data that had sub-hourly meteorological data (e.g., 10-min averages) available using several technical options: default mode, with various low wind speed beta options, and using the available sub-hourly meteorological data. These field study databases included (1) Mercer County, a North Dakota database featuring five SO2 monitors within 10 km of the Dakota Gasification Company's plant and the Antelope Valley Station power plant in an area of both flat and elevated terrain, and (2) a flat-terrain setting database with four SO2 monitors within 6 km of the Gibson Generating Station in southwest Indiana. Both sites featured regionally representative 10-m meteorological databases, with no significant terrain obstacles between the meteorological site and the emission sources. The low wind beta options show improvement in model performance helping to reduce some of the over-prediction biases currently present in AERMOD when run with regulatory default options. The overall findings with the low wind speed testing on these tall stack field-study databases indicate that AERMOD low wind speed options have a minor effect for flat terrain locations, but can have a significant effect for elevated terrain locations. The performance of AERMOD using low wind speed options leads to improved consistency of meteorological conditions associated with the highest observed and predicted concentration events. The available sub-hourly modeling results using the Sub-Hourly AERMOD Run Procedure (SHARP) are relatively unbiased and show that this alternative approach should be seriously considered to address situations dominated by low-wind meander conditions. AERMOD was evaluated with two tall stack databases (in North Dakota and Indiana) in areas of both flat and elevated terrain. AERMOD cases included the regulatory default mode, low wind speed beta options, and use of the Sub-Hourly AERMOD Run Procedure (SHARP). The low wind beta options show improvement in model performance (especially in higher terrain areas), helping to reduce some of the over-prediction biases currently present in regulatory default AERMOD. The SHARP results are relatively unbiased and show that this approach should be seriously considered to address situations dominated by low-wind meander conditions.

Effect of short-term room temperature storage on the microbial community in infant fecal samples.

PubMed

Guo, Yong; Li, Sheng-Hui; Kuang, Ya-Shu; He, Jian-Rong; Lu, Jin-Hua; Luo, Bei-Jun; Jiang, Feng-Ju; Liu, Yao-Zhong; Papasian, Christopher J; Xia, Hui-Min; Deng, Hong-Wen; Qiu, Xiu

2016-05-26

Sample storage conditions are important for unbiased analysis of microbial communities in metagenomic studies. Specifically, for infant gut microbiota studies, stool specimens are often exposed to room temperature (RT) conditions prior to analysis. This could lead to variations in structural and quantitative assessment of bacterial communities. To estimate such effects of RT storage, we collected feces from 29 healthy infants (0-3 months) and partitioned each sample into 5 portions to be stored for different lengths of time at RT before freezing at -80 °C. Alpha diversity did not differ between samples with storage time from 0 to 2 hours. The UniFrac distances and microbial composition analysis showed significant differences by testing among individuals, but not by testing between different time points at RT. Changes in the relative abundance of some specific (less common, minor) taxa were still found during storage at room temperature. Our results support previous studies in children and adults, and provided useful information for accurate characterization of infant gut microbiomes. In particular, our study furnished a solid foundation and justification for using fecal samples exposed to RT for less than 2 hours for comparative analyses between various medical conditions.

The influence of accuracy as a function of leader's bias: the role of trustworthiness in the psychology of procedural justice.

PubMed

De Cremer, David

2004-03-01

The present research examined the combined effect of accuracy of procedures and leader's bias on fairness judgments and the experience of positive emotions. The results of two studies showed that the strongest positive effects on both types of reactions were found when procedures were accurate and the leader was unbiased. In addition, accuracy of procedures only revealed an impact when the leader was perceived as unbiased rather than biased. Moreover, this interactive effect was found to be mediated, at least partly, by perceptions of trustworthiness. These findings show that more research is needed on examining different types of procedural fairness, both as single and combined predictors of people's reactions.

The effects of rehabilitative voir dire on juror bias and decision making.

PubMed

Crocker, Caroline B; Kovera, Margaret Bull

2010-06-01

During voir dire, judges frequently attempt to "rehabilitate" venirepersons who express an inability to be impartial. Venirepersons who agree to ignore their biases and base their verdict on the evidence and the law are eligible for jury service. In Experiment 1, biased and unbiased mock jurors participated in either a standard or rehabilitative voir dire conducted by a judge and watched a trial video. Rehabilitation influenced insanity defense attitudes and perceptions of the defendant's mental state, and decreased scaled guilt judgments compared to standard questioning. Although rehabilitation is intended to correct for partiality among biased jurors, rehabilitation similarly influenced biased and unbiased jurors. Experiment 2 found that watching rehabilitation did not influence jurors' perceptions of the judge's personal beliefs about the case.

Prediction and measurement results of radiation damage to CMOS devices on board spacecraft

NASA Technical Reports Server (NTRS)

Stassinopoulos, E. G.; Danchenko, V.; Cliff, R. A.; Sing, M.; Brucker, G. J.; Ohanian, R. S.

1977-01-01

Final results from the CMOS Radiation Effects Measurement (CREM) experiment flown on Explorer 55 are presented and discussed, based on about 15 months of observations and measurements. Conclusions are given relating to long-range annealing, effects of operating temperature on semiconductor performance in space, biased and unbiased P-MOS device degradation, unbiased n-channel device performance, changes in device transconductance, and the difference in ionization efficiency between Co-60 gamma rays and 1-Mev Van de Graaff electrons. The performance of devices in a heavily shielded electronic subsystem box within the spacecraft is evaluated and compared. Environment models and computational methods and their impact on device-degradation estimates are being reviewed to determine whether they permit cost-effective design of spacecraft.

Bases for qudits from a nonstandard approach to SU(2)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kibler, M. R., E-mail: kibler@ipnl.in2p3.fr

2011-06-15

Bases of finite-dimensional Hilbert spaces (in dimension d) of relevance for quantum information and quantum computation are constructed from angular momentum theory and su(2) Lie algebraic methods. We report on a formula for deriving in one step the (1 + p)p qupits (i.e., qudits with d = p a prime integer) of a complete set of 1 + p mutually unbiased bases in C{sup p}. Repeated application of the formula can be used for generating mutually unbiased bases in C{sup d} with d = p{sup e} (e {>=} 2) a power of a prime integer. A connection between mutually unbiasedmore » bases and the unitary group SU(d) is briefly discussed in the case d = p{sup e}.« less

Temporal steering and security of quantum key distribution with mutually unbiased bases against individual attacks

NASA Astrophysics Data System (ADS)

Bartkiewicz, Karol; Černoch, Antonín; Lemr, Karel; Miranowicz, Adam; Nori, Franco

2016-06-01

Temporal steering, which is a temporal analog of Einstein-Podolsky-Rosen steering, refers to temporal quantum correlations between the initial and final state of a quantum system. Our analysis of temporal steering inequalities in relation to the average quantum bit error rates reveals the interplay between temporal steering and quantum cloning, which guarantees the security of quantum key distribution based on mutually unbiased bases against individual attacks. The key distributions analyzed here include the Bennett-Brassard 1984 protocol and the six-state 1998 protocol by Bruss. Moreover, we define a temporal steerable weight, which enables us to identify a kind of monogamy of temporal correlation that is essential to quantum cryptography and useful for analyzing various scenarios of quantum causality.

[Studies of marker screening efficiency and corresponding influencing factors in QTL composite interval mapping].

PubMed

Gao, Yong-Ming; Wan, Ping

2002-06-01

Screening markers efficiently is the foundation of mapping QTLs by composite interval mapping. Main and interaction markers distinguished, besides using background control for genetic variation, could also be used to construct intervals of two-way searching for mapping QTLs with epistasis, which can save a lot of calculation time. Therefore, the efficiency of marker screening would affect power and precision of QTL mapping. A doubled haploid population with 200 individuals and 5 chromosomes was constructed, with 50 markers evenly distributed at 10 cM space. Among a total of 6 QTLs, one was placed on chromosome I, two linked on chromosome II, and the other three linked on chromosome IV. QTL setting included additive effects and epistatic effects of additive x additive, the corresponding QTL interaction effects were set if data were collected under multiple environments. The heritability was assumed to be 0.5 if no special declaration. The power of marker screening by stepwise regression, forward regression, and three methods for random effect prediction, e.g. best linear unbiased prediction (BLUP), linear unbiased prediction (LUP) and adjusted unbiased prediction (AUP), was studied and compared through 100 Monte Carlo simulations. The results indicated that the marker screening power by stepwise regression at 0.1, 0.05 and 0.01 significant level changed from 2% to 68%, the power changed from 2% to 72% by forward regression. The larger the QTL effects, the higher the marker screening power. While the power of marker screening by three random effect prediction was very low, the maximum was only 13%. That suggested that regression methods were much better than those by using the approaches of random effect prediction to identify efficient markers flanking QTLs, and forward selection method was more simple and efficient. The results of simulation study on heritability showed that heightening of both general heritability and interaction heritability of genotype x environments could enhance marker screening power, the former had a greater influence on QTLs with larger main and/or epistatic effects, while the later on QTLs with small main and/or epistatic effects. The simulation of 100 times was also conducted to study the influence of different marker number and density on marker screening power. It is indicated that the marker screening power would decrease if there were too many markers, especially with high density in a mapping population, which suggested that a mapping population with definite individuals could only hold limited markers. According to the simulation study, the reasonable number of markers should not be more than individuals. The simulation study of marker screening under multiple environments showed high total power of marker screening. In order to relieve the problem that marker screening power restricted the efficiency of QTL mapping, markers identified in multiple environments could be used to construct two search intervals.

Unified method to integrate and blend several, potentially related, sources of information for genetic evaluation.

PubMed

Vandenplas, Jérémie; Colinet, Frederic G; Gengler, Nicolas

2014-09-30

A condition to predict unbiased estimated breeding values by best linear unbiased prediction is to use simultaneously all available data. However, this condition is not often fully met. For example, in dairy cattle, internal (i.e. local) populations lead to evaluations based only on internal records while widely used foreign sires have been selected using internally unavailable external records. In such cases, internal genetic evaluations may be less accurate and biased. Because external records are unavailable, methods were developed to combine external information that summarizes these records, i.e. external estimated breeding values and associated reliabilities, with internal records to improve accuracy of internal genetic evaluations. Two issues of these methods concern double-counting of contributions due to relationships and due to records. These issues could be worse if external information came from several evaluations, at least partially based on the same records, and combined into a single internal evaluation. Based on a Bayesian approach, the aim of this research was to develop a unified method to integrate and blend simultaneously several sources of information into an internal genetic evaluation by avoiding double-counting of contributions due to relationships and due to records. This research resulted in equations that integrate and blend simultaneously several sources of information and avoid double-counting of contributions due to relationships and due to records. The performance of the developed equations was evaluated using simulated and real datasets. The results showed that the developed equations integrated and blended several sources of information well into a genetic evaluation. The developed equations also avoided double-counting of contributions due to relationships and due to records. Furthermore, because all available external sources of information were correctly propagated, relatives of external animals benefited from the integrated information and, therefore, more reliable estimated breeding values were obtained. The proposed unified method integrated and blended several sources of information well into a genetic evaluation by avoiding double-counting of contributions due to relationships and due to records. The unified method can also be extended to other types of situations such as single-step genomic or multi-trait evaluations, combining information across different traits.

The alarming problems of confounding equivalence using logistic regression models in the perspective of causal diagrams.

PubMed

Yu, Yuanyuan; Li, Hongkai; Sun, Xiaoru; Su, Ping; Wang, Tingting; Liu, Yi; Yuan, Zhongshang; Liu, Yanxun; Xue, Fuzhong

2017-12-28

Confounders can produce spurious associations between exposure and outcome in observational studies. For majority of epidemiologists, adjusting for confounders using logistic regression model is their habitual method, though it has some problems in accuracy and precision. It is, therefore, important to highlight the problems of logistic regression and search the alternative method. Four causal diagram models were defined to summarize confounding equivalence. Both theoretical proofs and simulation studies were performed to verify whether conditioning on different confounding equivalence sets had the same bias-reducing potential and then to select the optimum adjusting strategy, in which logistic regression model and inverse probability weighting based marginal structural model (IPW-based-MSM) were compared. The "do-calculus" was used to calculate the true causal effect of exposure on outcome, then the bias and standard error were used to evaluate the performances of different strategies. Adjusting for different sets of confounding equivalence, as judged by identical Markov boundaries, produced different bias-reducing potential in the logistic regression model. For the sets satisfied G-admissibility, adjusting for the set including all the confounders reduced the equivalent bias to the one containing the parent nodes of the outcome, while the bias after adjusting for the parent nodes of exposure was not equivalent to them. In addition, all causal effect estimations through logistic regression were biased, although the estimation after adjusting for the parent nodes of exposure was nearest to the true causal effect. However, conditioning on different confounding equivalence sets had the same bias-reducing potential under IPW-based-MSM. Compared with logistic regression, the IPW-based-MSM could obtain unbiased causal effect estimation when the adjusted confounders satisfied G-admissibility and the optimal strategy was to adjust for the parent nodes of outcome, which obtained the highest precision. All adjustment strategies through logistic regression were biased for causal effect estimation, while IPW-based-MSM could always obtain unbiased estimation when the adjusted set satisfied G-admissibility. Thus, IPW-based-MSM was recommended to adjust for confounders set.

Dynamic Histogram Analysis To Determine Free Energies and Rates from Biased Simulations.

PubMed

Stelzl, Lukas S; Kells, Adam; Rosta, Edina; Hummer, Gerhard

2017-12-12

We present an algorithm to calculate free energies and rates from molecular simulations on biased potential energy surfaces. As input, it uses the accumulated times spent in each state or bin of a histogram and counts of transitions between them. Optimal unbiased equilibrium free energies for each of the states/bins are then obtained by maximizing the likelihood of a master equation (i.e., first-order kinetic rate model). The resulting free energies also determine the optimal rate coefficients for transitions between the states or bins on the biased potentials. Unbiased rates can be estimated, e.g., by imposing a linear free energy condition in the likelihood maximization. The resulting "dynamic histogram analysis method extended to detailed balance" (DHAMed) builds on the DHAM method. It is also closely related to the transition-based reweighting analysis method (TRAM) and the discrete TRAM (dTRAM). However, in the continuous-time formulation of DHAMed, the detailed balance constraints are more easily accounted for, resulting in compact expressions amenable to efficient numerical treatment. DHAMed produces accurate free energies in cases where the common weighted-histogram analysis method (WHAM) for umbrella sampling fails because of slow dynamics within the windows. Even in the limit of completely uncorrelated data, where WHAM is optimal in the maximum-likelihood sense, DHAMed results are nearly indistinguishable. We illustrate DHAMed with applications to ion channel conduction, RNA duplex formation, α-helix folding, and rate calculations from accelerated molecular dynamics. DHAMed can also be used to construct Markov state models from biased or replica-exchange molecular dynamics simulations. By using binless WHAM formulated as a numerical minimization problem, the bias factors for the individual states can be determined efficiently in a preprocessing step and, if needed, optimized globally afterward.

Host Genome Influence on Gut Microbial Composition and Microbial Prediction of Complex Traits in Pigs.

PubMed

Camarinha-Silva, Amelia; Maushammer, Maria; Wellmann, Robin; Vital, Marius; Preuss, Siegfried; Bennewitz, Jörn

2017-07-01

The aim of the present study was to analyze the interplay between gastrointestinal tract (GIT) microbiota, host genetics, and complex traits in pigs using extended quantitative-genetic methods. The study design consisted of 207 pigs that were housed and slaughtered under standardized conditions, and phenotyped for daily gain, feed intake, and feed conversion rate. The pigs were genotyped with a standard 60 K SNP chip. The GIT microbiota composition was analyzed by 16S rRNA gene amplicon sequencing technology. Eight from 49 investigated bacteria genera showed a significant narrow sense host heritability, ranging from 0.32 to 0.57. Microbial mixed linear models were applied to estimate the microbiota variance for each complex trait. The fraction of phenotypic variance explained by the microbial variance was 0.28, 0.21, and 0.16 for daily gain, feed conversion, and feed intake, respectively. The SNP data and the microbiota composition were used to predict the complex traits using genomic best linear unbiased prediction (G-BLUP) and microbial best linear unbiased prediction (M-BLUP) methods, respectively. The prediction accuracies of G-BLUP were 0.35, 0.23, and 0.20 for daily gain, feed conversion, and feed intake, respectively. The corresponding prediction accuracies of M-BLUP were 0.41, 0.33, and 0.33. Thus, in addition to SNP data, microbiota abundances are an informative source of complex trait predictions. Since the pig is a well-suited animal for modeling the human digestive tract, M-BLUP, in addition to G-BLUP, might be beneficial for predicting human predispositions to some diseases, and, consequently, for preventative and personalized medicine. Copyright © 2017 by the Genetics Society of America.

Untargeted Metabolomics Reveals Predominant Alterations in Lipid Metabolism Following Light Exposure in Broccoli Sprouts

PubMed Central

Maldini, Mariateresa; Natella, Fausta; Baima, Simona; Morelli, Giorgio; Scaccini, Cristina; Langridge, James; Astarita, Giuseppe

2015-01-01

The consumption of vegetables belonging to the family Brassicaceae (e.g., broccoli and cauliflower) is linked to a reduced incidence of cancer and cardiovascular diseases. The molecular composition of such plants is strongly affected by growing conditions. Here we developed an unbiased metabolomics approach to investigate the effect of light and dark exposure on the metabolome of broccoli sprouts and we applied such an approach to provide a bird’s-eye view of the overall metabolic response after light exposure. Broccoli seeds were germinated and grown hydroponically for five days in total darkness or with a light/dark photoperiod (16 h light/8 h dark cycle). We used an ultra-performance liquid-chromatography system coupled to an ion-mobility, time-of-flight mass spectrometer to profile the large array of metabolites present in the sprouts. Differences at the metabolite level between groups were analyzed using multivariate statistical analyses, including principal component analysis and correlation analysis. Altered metabolites were identified by searching publicly available and in-house databases. Metabolite pathway analyses were used to support the identification of subtle but significant changes among groups of related metabolites that may have gone unnoticed with conventional approaches. Besides the chlorophyll pathway, light exposure activated the biosynthesis and metabolism of sterol lipids, prenol lipids, and polyunsaturated lipids, which are essential for the photosynthetic machinery. Our results also revealed that light exposure increased the levels of polyketides, including flavonoids, and oxylipins, which play essential roles in the plant’s developmental processes and defense mechanism against herbivores. This study highlights the significant contribution of light exposure to the ultimate metabolic phenotype, which might affect the cellular physiology and nutritional value of broccoli sprouts. Furthermore, this study highlights the potential of an unbiased omics approach for the comprehensive study of the metabolism. PMID:26084047

MODIS observations of cyanobacterial risks in a eutrophic lake: Implications for long-term safety evaluation in drinking-water source.

PubMed

Duan, Hongtao; Tao, Min; Loiselle, Steven Arthur; Zhao, Wei; Cao, Zhigang; Ma, Ronghua; Tang, Xiaoxian

2017-10-01

The occurrence and related risks from cyanobacterial blooms have increased world-wide over the past 40 years. Information on the abundance and distribution of cyanobacteria is fundamental to support risk assessment and management activities. In the present study, an approach based on Empirical Orthogonal Function (EOF) analysis was used to estimate the concentrations of chlorophyll a (Chla) and the cyanobacterial biomarker pigment phycocyanin (PC) using data from the MODerate resolution Imaging Spectroradiometer (MODIS) in Lake Chaohu (China's fifth largest freshwater lake). The approach was developed and tested using fourteen years (2000-2014) of MODIS images, which showed significant spatial and temporal variability of the PC:Chla ratio, an indicator of cyanobacterial dominance. The results had unbiased RMS uncertainties of <60% for Chla ranging between 10 and 300 μg/L, and unbiased RMS uncertainties of <65% for PC between 10 and 500 μg/L. Further analysis showed the importance of nutrient and climate conditions for this dominance. Low TN:TP ratios (<29:1) and elevated temperatures were found to influence the seasonal shift of phytoplankton community. The resultant MODIS Chla and PC products were then used for cyanobacterial risk mapping with a decision tree classification model. The resulting Water Quality Decision Matrix (WQDM) was designed to assist authorities in the identification of possible intake areas, as well as specific months when higher frequency monitoring and more intense water treatment would be required if the location of the present intake area remained the same. Remote sensing cyanobacterial risk mapping provides a new tool for reservoir and lake management programs. Copyright © 2017 Elsevier Ltd. All rights reserved.

Class Enumeration and Parameter Recovery of Growth Mixture Modeling and Second-Order Growth Mixture Modeling in the Presence of Measurement Noninvariance between Latent Classes

PubMed Central

Kim, Eun Sook; Wang, Yan

2017-01-01

Population heterogeneity in growth trajectories can be detected with growth mixture modeling (GMM). It is common that researchers compute composite scores of repeated measures and use them as multiple indicators of growth factors (baseline performance and growth) assuming measurement invariance between latent classes. Considering that the assumption of measurement invariance does not always hold, we investigate the impact of measurement noninvariance on class enumeration and parameter recovery in GMM through a Monte Carlo simulation study (Study 1). In Study 2, we examine the class enumeration and parameter recovery of the second-order growth mixture modeling (SOGMM) that incorporates measurement models at the first order level. Thus, SOGMM estimates growth trajectory parameters with reliable sources of variance, that is, common factor variance of repeated measures and allows heterogeneity in measurement parameters between latent classes. The class enumeration rates are examined with information criteria such as AIC, BIC, sample-size adjusted BIC, and hierarchical BIC under various simulation conditions. The results of Study 1 showed that the parameter estimates of baseline performance and growth factor means were biased to the degree of measurement noninvariance even when the correct number of latent classes was extracted. In Study 2, the class enumeration accuracy of SOGMM depended on information criteria, class separation, and sample size. The estimates of baseline performance and growth factor mean differences between classes were generally unbiased but the size of measurement noninvariance was underestimated. Overall, SOGMM is advantageous in that it yields unbiased estimates of growth trajectory parameters and more accurate class enumeration compared to GMM by incorporating measurement models. PMID:28928691

An Appraisal of Some Energy Films.

ERIC Educational Resources Information Center

Dowling, John

1979-01-01

Discusses problems of achieving balance and objectivity in dealing with the energy crisis, and describes ten instructional films that might be useful in achieving objective, unbiased instruction. (CMV)

Act on Numbers: Numerical Magnitude Influences Selection and Kinematics of Finger Movement

PubMed Central

Rugani, Rosa; Betti, Sonia; Ceccarini, Francesco; Sartori, Luisa

2017-01-01

In the past decade hand kinematics has been reliably adopted for investigating cognitive processes and disentangling debated topics. One of the most controversial issues in numerical cognition literature regards the origin – cultural vs. genetically driven – of the mental number line (MNL), oriented from left (small numbers) to right (large numbers). To date, the majority of studies have investigated this effect by means of response times, whereas studies considering more culturally unbiased measures such as kinematic parameters are rare. Here, we present a new paradigm that combines a “free response” task with the kinematic analysis of movement. Participants were seated in front of two little soccer goals placed on a table, one on the left and one on the right side. They were presented with left- or right-directed arrows and they were instructed to kick a small ball with their right index toward the goal indicated by the arrow. In a few test trials participants were presented also with a small (2) or a large (8) number, and they were allowed to choose the kicking direction. Participants performed more left responses with the small number and more right responses with the large number. The whole kicking movement was segmented in two temporal phases in order to make a hand kinematics’ fine-grained analysis. The Kick Preparation and Kick Finalization phases were selected on the basis of peak trajectory deviation from the virtual midline between the two goals. Results show an effect of both small and large numbers on action execution timing. Participants were faster to finalize the action when responding to small numbers toward the left and to large number toward the right. Here, we provide the first experimental demonstration which highlights how numerical processing affects action execution in a new and not-overlearned context. The employment of this innovative and unbiased paradigm will permit to disentangle the role of nature and culture in shaping the direction of MNL and the role of finger in the acquisition of numerical skills. Last but not least, similar paradigms will allow to determine how cognition can influence action execution. PMID:28912743

Emergence of dormant conditioned incentive approach by conditioned withdrawal in nicotine addiction.

PubMed

Scott, Daniel; Hiroi, Noboru

2010-10-15

Nicotine is one of the determinants for the development of persistent smoking, and this maladaptive behavior is characterized by many symptoms, including withdrawal and nicotine seeking. The process by which withdrawal affects nicotine seeking is poorly understood. The impact of a withdrawal-associated cue on nicotine (.2 mg/kg)-conditioned place preference was assessed in male C57BL/6J mice (n = 8-17/group). To establish a cue selectively associated with withdrawal distinct from those associated with nicotine, a tone was paired with withdrawal in their home cages; mice were chronically exposed to nicotine (200 μg/mL for 15 days) from drinking water in their home cages and received the nicotinic acetylcholine receptor antagonist mecamylamine (2.5 mg/kg) to precipitate withdrawal in the presence of a tone. The effect of the withdrawal-associated tone on nicotine-conditioned place preference was then evaluated in the place-conditioning apparatus after a delay, when nicotine-conditioned place preference spontaneously disappeared. A cue associated with precipitated withdrawal reactivated the dormant effect of nicotine-associated cues on conditioned place preference. This effect occurred during continuous exposure to nicotine but not during abstinence. A conditioned withdrawal cue could directly amplify the incentive properties of cues associated with nicotine. This observation extends the contemporary incentive account of the role of withdrawal in addiction to cue-cue interaction. Copyright © 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Treatment effects model for assessing disease management: measuring outcomes and strengthening program management.

PubMed

Wendel, Jeanne; Dumitras, Diana

2005-06-01

This paper describes an analytical methodology for obtaining statistically unbiased outcomes estimates for programs in which participation decisions may be correlated with variables that impact outcomes. This methodology is particularly useful for intraorganizational program evaluations conducted for business purposes. In this situation, data is likely to be available for a population of managed care members who are eligible to participate in a disease management (DM) program, with some electing to participate while others eschew the opportunity. The most pragmatic analytical strategy for in-house evaluation of such programs is likely to be the pre-intervention/post-intervention design in which the control group consists of people who were invited to participate in the DM program, but declined the invitation. Regression estimates of program impacts may be statistically biased if factors that impact participation decisions are correlated with outcomes measures. This paper describes an econometric procedure, the Treatment Effects model, developed to produce statistically unbiased estimates of program impacts in this type of situation. Two equations are estimated to (a) estimate the impacts of patient characteristics on decisions to participate in the program, and then (b) use this information to produce a statistically unbiased estimate of the impact of program participation on outcomes. This methodology is well-established in economics and econometrics, but has not been widely applied in the DM outcomes measurement literature; hence, this paper focuses on one illustrative application.

Species richness in soil bacterial communities: a proposed approach to overcome sample size bias.

PubMed

Youssef, Noha H; Elshahed, Mostafa S

2008-09-01

Estimates of species richness based on 16S rRNA gene clone libraries are increasingly utilized to gauge the level of bacterial diversity within various ecosystems. However, previous studies have indicated that regardless of the utilized approach, species richness estimates obtained are dependent on the size of the analyzed clone libraries. We here propose an approach to overcome sample size bias in species richness estimates in complex microbial communities. Parametric (Maximum likelihood-based and rarefaction curve-based) and non-parametric approaches were used to estimate species richness in a library of 13,001 near full-length 16S rRNA clones derived from soil, as well as in multiple subsets of the original library. Species richness estimates obtained increased with the increase in library size. To obtain a sample size-unbiased estimate of species richness, we calculated the theoretical clone library sizes required to encounter the estimated species richness at various clone library sizes, used curve fitting to determine the theoretical clone library size required to encounter the "true" species richness, and subsequently determined the corresponding sample size-unbiased species richness value. Using this approach, sample size-unbiased estimates of 17,230, 15,571, and 33,912 were obtained for the ML-based, rarefaction curve-based, and ACE-1 estimators, respectively, compared to bias-uncorrected values of 15,009, 11,913, and 20,909.

Identification of Rare Lewis Oligosaccharide Conformers in Aqueous Solution Using Enhanced Sampling Molecular Dynamics.

PubMed

Alibay, Irfan; Burusco, Kepa K; Bruce, Neil J; Bryce, Richard A

2018-03-08

Determining the conformations accessible to carbohydrate ligands in aqueous solution is important for understanding their biological action. In this work, we evaluate the conformational free-energy surfaces of Lewis oligosaccharides in explicit aqueous solvent using a multidimensional variant of the swarm-enhanced sampling molecular dynamics (msesMD) method; we compare with multi-microsecond unbiased MD simulations, umbrella sampling, and accelerated MD approaches. For the sialyl Lewis A tetrasaccharide, msesMD simulations in aqueous solution predict conformer landscapes in general agreement with the other biased methods and with triplicate unbiased 10 μs trajectories; these simulations find a predominance of closed conformer and a range of low-occupancy open forms. The msesMD simulations also suggest closed-to-open transitions in the tetrasaccharide are facilitated by changes in ring puckering of its GlcNAc residue away from the 4 C 1 form, in line with previous work. For sialyl Lewis X tetrasaccharide, msesMD simulations predict a minor population of an open form in solution corresponding to a rare lectin-bound pose observed crystallographically. Overall, from comparison with biased MD calculations, we find that triplicate 10 μs unbiased MD simulations may not be enough to fully sample glycan conformations in aqueous solution. However, the computational efficiency and intuitive approach of the msesMD method suggest potential for its application in glycomics as a tool for analysis of oligosaccharide conformation.

Identification and characterization of Highlands J virus from a Mississippi sandhill crane using unbiased next-generation sequencing

USGS Publications Warehouse

Ip, Hon S.; Wiley, Michael R.; Long, Renee; Gustavo, Palacios; Shearn-Bochsler, Valerie; Whitehouse, Chris A.

2014-01-01

Advances in massively parallel DNA sequencing platforms, commonly termed next-generation sequencing (NGS) technologies, have greatly reduced time, labor, and cost associated with DNA sequencing. Thus, NGS has become a routine tool for new viral pathogen discovery and will likely become the standard for routine laboratory diagnostics of infectious diseases in the near future. This study demonstrated the application of NGS for the rapid identification and characterization of a virus isolated from the brain of an endangered Mississippi sandhill crane. This bird was part of a population restoration effort and was found in an emaciated state several days after Hurricane Isaac passed over the refuge in Mississippi in 2012. Post-mortem examination had identified trichostrongyliasis as the possible cause of death, but because a virus with morphology consistent with a togavirus was isolated from the brain of the bird, an arboviral etiology was strongly suspected. Because individual molecular assays for several known arboviruses were negative, unbiased NGS by Illumina MiSeq was used to definitively identify and characterize the causative viral agent. Whole genome sequencing and phylogenetic analysis revealed the viral isolate to be the Highlands J virus, a known avian pathogen. This study demonstrates the use of unbiased NGS for the rapid detection and characterization of an unidentified viral pathogen and the application of this technology to wildlife disease diagnostics and conservation medicine.

Sodium Binding Sites and Permeation Mechanism in the NaChBac Channel: A Molecular Dynamics Study.

PubMed

Guardiani, Carlo; Rodger, P Mark; Fedorenko, Olena A; Roberts, Stephen K; Khovanov, Igor A

2017-03-14

NaChBac was the first discovered bacterial sodium voltage-dependent channel, yet computational studies are still limited due to the lack of a crystal structure. In this work, a pore-only construct built using the NavMs template was investigated using unbiased molecular dynamics and metadynamics. The potential of mean force (PMF) from the unbiased run features four minima, three of which correspond to sites IN, CEN, and HFS discovered in NavAb. During the run, the selectivity filter (SF) is spontaneously occupied by two ions, and frequent access of a third one is often observed. In the innermost sites IN and CEN, Na + is fully hydrated by six water molecules and occupies an on-axis position. In site HFS sodium interacts with a glutamate and a serine from the same subunit and is forced to adopt an off-axis placement. Metadynamics simulations biasing one and two ions show an energy barrier in the SF that prevents single-ion permeation. An analysis of the permeation mechanism was performed both computing minimum energy paths in the axial-axial PMF and through a combination of Markov state modeling and transition path theory. Both approaches reveal a knock-on mechanism involving at least two but possibly three ions. The currents predicted from the unbiased simulation using linear response theory are in excellent agreement with single-channel patch-clamp recordings.

On the context dependency of implicit self-esteem in social anxiety disorder.

PubMed

Hiller, Thomas S; Steffens, Melanie C; Ritter, Viktoria; Stangier, Ulrich

2017-12-01

Cognitive models assume that negative self-evaluations are automatically activated in individuals with Social Anxiety Disorder (SAD) during social situations, increasing their individual level of anxiety. This study examined automatic self-evaluations (i.e., implicit self-esteem) and state anxiety in a group of individuals with SAD (n = 45) and a non-clinical comparison group (NC; n = 46). Participants were randomly assigned to either a speech condition with social threat induction (giving an impromptu speech) or to a no-speech condition without social threat induction. We measured implicit self-esteem with an Implicit Association Test (IAT). Implicit self-esteem differed significantly between SAD and NC groups under the speech condition but not under the no-speech condition. The SAD group showed lower implicit self-esteem than the NC group under the speech-condition. State anxiety was significantly higher under the speech condition than under the no-speech condition in the SAD group but not in the NC group. Mediation analyses supported the idea that for the SAD group, the effect of experimental condition on state anxiety was mediated by implicit self-esteem. The causal relation between implicit self-esteem and state anxiety could not be determined. The findings corroborate hypotheses derived from cognitive models of SAD: Automatic self-evaluations were negatively biased in individuals with SAD facing social threat and showed an inverse relationship to levels of state anxiety. However, automatic self-evaluations in individuals with SAD can be unbiased (similar to NC) in situations without social threat. Copyright © 2017 Elsevier Ltd. All rights reserved.

ETHANOL-INDUCED LOCOMOTOR ACTIVITY IN ADOLESCENT RATS AND THE RELATIONSHIP WITH ETHANOL-INDUCED CONDITIONED PLACE PREFERENCE AND CONDITIONED TASTE AVERSION

PubMed Central

Acevedo, María Belén; Nizhnikov, Michael E.; Spear, Norman E.; Molina, Juan C.; Pautassi, Ricardo Marcos

2012-01-01

Adolescent rats exhibit ethanol-induced locomotor activity (LMA), which is considered an index of ethanol’s motivational properties likely to predict ethanol self-administration, but few studies have reported or correlated ethanol-induced LMA with conditioned place preference by ethanol at this age. The present study assessed age-related differences in ethanol’s motor stimulating effects and analysed the association between ethanol-induced LMA and conventional measures of ethanol-induced reinforcement. Experiment 1 compared ethanol-induced LMA in adolescent and adult rats. Subsequent experiments analyzed ethanol-induced conditioned place preference and conditioned taste aversion in adolescent rats evaluated for ethanol-induced LMA. Adolescent rats exhibit a robust LMA after high-dose ethanol. Ethanol-induced LMA was fairly similar across adolescents and adults. As expected, adolescents were sensitive to ethanol’s aversive reinforcement, but they also exhibited conditioned place preference. These measures of ethanol reinforcement, however, were not related to ethanol-induced LMA. Spontaneous LMA in an open field was, however, negatively associated with ethanol-induced CTA. PMID:22592597

Power and On-Board Propulsion System Benefit Studies at NASA GRC

NASA Technical Reports Server (NTRS)

Hoffman, David J.

2000-01-01

This paper discusses the value of systems studies that provide unbiased 'honest broker' assessments of the quantified benefits afforded by advanced technologies for specific missions. The organization, format, and approach used by the NASA Glenn Research Center (GRC) Systems Assessment Team (SAT) to perform system studies for the GRC advanced power and on-board propulsion technology development program is described. Three levels of assessments and a sensitivity analysis are explained and example results are presented. The impact of system studies results and some of the main challenges associated with systems studies are identified. A call for collaboration is made where system studies of all types from all organizations can be reviewed, providing a forum for the widest peer review to ensure accurate and unbiased technical content, and to avoid needless duplication.

Separate spatial Holographic-Hamiltonian soliton pairs and solitons interaction in an unbiased series photorefractive crystal circuit.

PubMed

Cai, Xin; Liu, Jinsong; Wang, Shenglie

2009-02-16

This paper presents calculations for an idea in photorefractive spatial soliton, namely, a dissipative holographic soliton and a Hamiltonian soliton in one dimension form in an unbiased series photorefractive crystal circuit consisting of two photorefractive crystals of which at least one must be photovoltaic. The two solitons are known collectively as a separate Holographic-Hamiltonian spatial soliton pair and there are two types: dark-dark and bright-dark if only one crystal of the circuit is photovoltaic. The numerical results show that the Hamiltonian soliton in a soliton pair can affect the holographic one by the light-induced current whereas the effect of the holographic soliton on the Hamiltonian soliton is too weak to be ignored, i.e., the holographic soliton cannot affect the Hamiltonian one.

Host Galaxy Properties of SWIFT Hard X-ray Selected AGN

NASA Astrophysics Data System (ADS)

Koss, Michael; Mushotzky, R.; Veilleux, S.; Winter, L.

2010-01-01

Surveys of AGN taken in the optical, UV, and soft X-rays miss an important population of obscured AGN only visible in the hard X-rays and mid-IR wavelengths. The SWIFT BAT survey in the hard X-ray range (14-195 keV) has provided a uniquely unbiased sample of 258 AGN unaffected by galactic or circumnuclear absorption. Optical imaging of this unbiased sample provides a new opportunity to understand how the environments of the host galaxies are linked to AGN. In 2008, we observed 110 of these targets at Kitt Peak with the 2.1m in the SDSS ugriz bands over 17 nights. Using these observations and SDSS data we review the relationships between color, morphology, merger activity, star formation, and AGN luminosity.

Communication: Improved ab initio molecular dynamics by minimally biasing with experimental data

NASA Astrophysics Data System (ADS)

White, Andrew D.; Knight, Chris; Hocky, Glen M.; Voth, Gregory A.

2017-01-01

Accounting for electrons and nuclei simultaneously is a powerful capability of ab initio molecular dynamics (AIMD). However, AIMD is often unable to accurately reproduce properties of systems such as water due to inaccuracies in the underlying electronic density functionals. This shortcoming is often addressed by added empirical corrections and/or increasing the simulation temperature. We present here a maximum-entropy approach to directly incorporate limited experimental data via a minimal bias. Biased AIMD simulations of water and an excess proton in water are shown to give significantly improved properties both for observables which were biased to match experimental data and for unbiased observables. This approach also yields new physical insight into inaccuracies in the underlying density functional theory as utilized in the unbiased AIMD.

Communication: Improved ab initio molecular dynamics by minimally biasing with experimental data.

PubMed

White, Andrew D; Knight, Chris; Hocky, Glen M; Voth, Gregory A

2017-01-28

Accounting for electrons and nuclei simultaneously is a powerful capability of ab initio molecular dynamics (AIMD). However, AIMD is often unable to accurately reproduce properties of systems such as water due to inaccuracies in the underlying electronic density functionals. This shortcoming is often addressed by added empirical corrections and/or increasing the simulation temperature. We present here a maximum-entropy approach to directly incorporate limited experimental data via a minimal bias. Biased AIMD simulations of water and an excess proton in water are shown to give significantly improved properties both for observables which were biased to match experimental data and for unbiased observables. This approach also yields new physical insight into inaccuracies in the underlying density functional theory as utilized in the unbiased AIMD.

Bipartite entangled stabilizer mutually unbiased bases as maximum cliques of Cayley graphs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dam, Wim van; Howard, Mark; Department of Physics, University of California, Santa Barbara, California 93106

2011-07-15

We examine the existence and structure of particular sets of mutually unbiased bases (MUBs) in bipartite qudit systems. In contrast to well-known power-of-prime MUB constructions, we restrict ourselves to using maximally entangled stabilizer states as MUB vectors. Consequently, these bipartite entangled stabilizer MUBs (BES MUBs) provide no local information, but are sufficient and minimal for decomposing a wide variety of interesting operators including (mixtures of) Jamiolkowski states, entanglement witnesses, and more. The problem of finding such BES MUBs can be mapped, in a natural way, to that of finding maximum cliques in a family of Cayley graphs. Some relationships withmore » known power-of-prime MUB constructions are discussed, and observables for BES MUBs are given explicitly in terms of Pauli operators.« less

Intrinsic Atomic Orbitals: An Unbiased Bridge between Quantum Theory and Chemical Concepts.

PubMed

Knizia, Gerald

2013-11-12

Modern quantum chemistry can make quantitative predictions on an immense array of chemical systems. However, the interpretation of those predictions is often complicated by the complex wave function expansions used. Here we show that an exceptionally simple algebraic construction allows for defining atomic core and valence orbitals, polarized by the molecular environment, which can exactly represent self-consistent field wave functions. This construction provides an unbiased and direct connection between quantum chemistry and empirical chemical concepts, and can be used, for example, to calculate the nature of bonding in molecules, in chemical terms, from first principles. In particular, we find consistency with electronegativities (χ), C 1s core-level shifts, resonance substituent parameters (σR), Lewis structures, and oxidation states of transition-metal complexes.

Demonstration of an all-optical feed-forward delay line buffer using the quadratic Stark effect and two-photon absorption in an SOA.

PubMed

Soto, Horacio; Tong, Miriam A; Domínguez, Juan C; Muraoka, Ramón

2017-09-04

We have inserted into an unbiased semiconductor optical amplifier (SOA) a powerful control beam, with photon energy slightly smaller than that of the band-gap of its active region, for exciting two-photon absorption and the quadratic Stark effect. For the available SOA, we estimated these phenomena generated a nonlinear absorption coefficient β= -865 cm/GW and induced an appreciable birefringence inside the amplifier waveguide, which significantly modified the polarization-state of a probe beam. Based on these effects, we have experimentally demonstrated the operation of an all-optical buffer, using an 80 Gb/s optical pulse comb, as well as an unbiased SOA, which was therefore, devoid of amplified spontaneous emission and pattern effects.

Unbiased phosphoproteomic method identifies the initial effects of a methacrylic acid copolymer on macrophages

PubMed Central

Chamberlain, Michael Dean; Wells, Laura A.; Lisovsky, Alexandra; Guo, Hongbo; Isserlin, Ruth; Talior-Volodarsky, Ilana; Mahou, Redouan; Emili, Andrew; Sefton, Michael V.

2015-01-01

An unbiased phosphoproteomic method was used to identify biomaterial-associated changes in the phosphorylation patterns of macrophage-like cells. The phosphorylation differences between differentiated THP1 (dTHP1) cells treated for 10, 20, or 30 min with a vascular regenerative methacrylic acid (MAA) copolymer or a control methyl methacrylate (MM) copolymer were determined by MS. There were 1,470 peptides (corresponding to 729 proteins) that were differentially phosphorylated in dTHP1 cells treated with the two materials with a greater cellular response to MAA treatment. In addition to identifying pathways (such as integrin signaling and cytoskeletal arrangement) that are well known to change with cell–material interaction, previously unidentified pathways, such as apoptosis and mRNA splicing, were also discovered. PMID:26261332

Bipartite entangled stabilizer mutually unbiased bases as maximum cliques of Cayley graphs

NASA Astrophysics Data System (ADS)

van Dam, Wim; Howard, Mark

2011-07-01

We examine the existence and structure of particular sets of mutually unbiased bases (MUBs) in bipartite qudit systems. In contrast to well-known power-of-prime MUB constructions, we restrict ourselves to using maximally entangled stabilizer states as MUB vectors. Consequently, these bipartite entangled stabilizer MUBs (BES MUBs) provide no local information, but are sufficient and minimal for decomposing a wide variety of interesting operators including (mixtures of) Jamiołkowski states, entanglement witnesses, and more. The problem of finding such BES MUBs can be mapped, in a natural way, to that of finding maximum cliques in a family of Cayley graphs. Some relationships with known power-of-prime MUB constructions are discussed, and observables for BES MUBs are given explicitly in terms of Pauli operators.

Zero-bias microwave detectors based on array of nanorectifiers coupled with a dipole antenna

NASA Astrophysics Data System (ADS)

Kasjoo, Shahrir R.; Singh, Arun K.; Mat Isa, Siti S.; Ramli, Muhammad M.; Mohamad Isa, Muammar; Ahmad, Norhawati; Mohd Nor, Nurul I.; Khalid, Nazuhusna; Song, Ai Min

2016-04-01

We report on zero-bias microwave detection using a large array of unipolar nanodevices, known as the self-switching diodes (SSDs). The large array was realized in a single lithography step without the need of interconnection layers, hence allowing for a simple and low-cost fabrication process. The SSD array was coupled with a narrowband dipole antenna with a resonant frequency of 890 MHz, to form a simple rectenna (rectifying antenna). The extrinsic voltage responsivity and noise-equivalent-power (NEP) of the rectenna were ∼70 V/W and ∼0.18 nW/Hz1/2, respectively, measured in the far-field region at unbiased condition. Nevertheless, the estimated intrinsic voltage responsivity can achieve up to ∼5 kV/W with NEP of ∼2.6 pW/Hz1/2.

[The application of stereology in radiology imaging and cell biology fields].

PubMed

Hu, Na; Wang, Yan; Feng, Yuanming; Lin, Wang

2012-08-01

Stereology is an interdisciplinary method for 3D morphological study developed from mathematics and morphology. It is widely used in medical image analysis and cell biology studies. Because of its unbiased, simple, fast, reliable and non-invasive characteristics, stereology has been widely used in biomedical areas for quantitative analysis and statistics, such as histology, pathology and medical imaging. Because the stereological parameters show distinct differences in different pathology, many scholars use stereological methods to do quantitative analysis in their studies in recent years, for example, in the areas of the condition of cancer cells, tumor grade, disease development and the patient's prognosis, etc. This paper describes the stereological concept and estimation methods, also illustrates the applications of stereology in the fields of CT images, MRI images and cell biology, and finally reflects the universality, the superiority and reliability of stereology.

Public information, dissemination, and behavior analysis

PubMed Central

Morris, Edward K.

1985-01-01

Behavior analysts have become increasingly concerned about inaccuracies and misconceptions in the public, educational, and professional information portraying their activities, but have done little to correct these views. The present paper has two purposes in this regard. First, the paper describes some of the conditions that have given rise to these concerns. Second, and more important, the paper surveys various procedures and programs for the dissemination of public information that may correct inaccuracies and misconceptions. Special consideration is also given to issues involving (a) the assessment of the problem, (b) the content and means of dissemination, (c) the possible contributions of behavior analysts to current misunderstandings, and (d) relationships between behavior analysts and the media. The dissemination of accurate and unbiased information constitutes an important new undertaking for behavior analysis. The future of the field may depend in part on such activity. PMID:22478623

Performance and life evaluation of advanced battery technologies for electric vehicle applications

NASA Astrophysics Data System (ADS)

Deluca, W. H.; Gillie, K. R.; Kulaga, J. E.; Smaga, J. A.; Tummillo, A. F.; Webster, C. E.

Advanced battery technology evaluations are performed under simulated electric vehicle (EV) operating conditions at the Argonne Analysis and Diagnostic Laboratory (ADL). The ADL provides a common basis for both performance characterization and life evaluation with unbiased application of tests and analyses. This paper summarizes the performance characterizations and life evaluations conducted in 1990 on nine single cells and fifteen 3- to 360-cell modules that encompass six technologies: (Na/S, Zn/Br, Ni/Fe, Ni/Cd, Ni-metal hydride, and lead-acid). These evaluations were performed for the Department of Energy and Electric Power Research Institute. The results provide battery users, developers, and program managers an interim measure of the progress being made in battery R and D programs, a comparison of battery technologies, and a source of basic data for modelling and continuing R and D.

SIC-POVMS and MUBS: Geometrical Relationships in Prime Dimension

NASA Astrophysics Data System (ADS)

Appleby, D. M.

2009-03-01

The paper concerns Weyl-Heisenberg covariant SIC-POVMs (symmetric informationally complete positive operator valued measures) and full sets of MUBs (mutually unbiased bases) in prime dimension. When represented as vectors in generalized Bloch space a SIC-POVM forms a d2-1 dimensional regular simplex (d being the Hilbert space dimension). By contrast, the generalized Bloch vectors representing a full set of MUBs form d+1 mutually orthogonal d-1 dimensional regular simplices. In this paper we show that, in the Weyl-Heisenberg case, there are some simple geometrical relationships between the single SIC-POVM simplex and the d+1 MUB simplices. We go on to give geometrical interpretations of the minimum uncertainty states introduced by Wootters and Sussman, and by Appleby, Dang and Fuchs, and of the fiduciality condition given by Appleby, Dang and Fuchs.

Fast Charge Battery Electric Transit Bus In-Use Fleet Evaluation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Prohaska, Robert; Kelly, Kenneth; Eudy, Leslie

2016-07-25

The focus of this interim fleet evaluation is to characterize and evaluate the operating behavior of Foothill Transit's fast charge battery electric buses (BEBs). Future research will compare the BEBs' performance to conventional vehicles. In an effort to better understand the impacts of drive cycle characteristics on advanced vehicle technologies, researchers at the National Renewable Energy Laboratory analyzed over 148,000 km of in-use operational data, including driving and charging events. This analysis provides an unbiased evaluation of advanced vehicle technologies in real-world operation demonstrating the importance of understanding the effects of road grade and heating, ventilating and air conditioning requirementsmore » when deploying electric vehicles. The results of this analysis show that the Proterra BE35 demonstrated an operating energy efficiency of 1.34 kWh/km over the data reporting period.« less

Fast Charge Battery Electric Transit Bus In-Use Fleet Evaluation: Preprint

DOE Office of Scientific and Technical Information (OSTI.GOV)

Prohaska, Robert; Eudy, Leslie; Kelly, Kenneth

2016-05-06

The focus of this interim fleet evaluation is to characterize and evaluate the operating behavior of Foothill Transit's fast charge battery electric buses (BEBs). Future research will compare the BEBs' performance to conventional vehicles. In an effort to better understand the impacts of drive cycle characteristics on advanced vehicle technologies, researchers at the National Renewable Energy Laboratory analyzed over 148,000 km of in-use operational data, including driving and charging events. This analysis provides an unbiased evaluation of advanced vehicle technologies in real-world operation demonstrating the importance of understanding the effects of road grade and heating, ventilating and air conditioning requirementsmore » when deploying electric vehicles. The results of this analysis show that the Proterra BE35 demonstrated an operating energy efficiency of 1.34 kWh/km over the data reporting period.« less

A robust classic.

PubMed

Kutzner, Florian; Vogel, Tobias; Freytag, Peter; Fiedler, Klaus

2011-01-01

In the present research, we argue for the robustness of illusory correlations (ICs, Hamilton & Gifford, 1976) regarding two boundary conditions suggested in previous research. First, we argue that ICs are maintained under extended experience. Using simulations, we derive conflicting predictions. Whereas noise-based accounts predict ICs to be maintained (Fielder, 2000; Smith, 1991), a prominent account based on discrepancy-reducing feedback learning predicts ICs to disappear (Van Rooy et al., 2003). An experiment involving 320 observations with majority and minority members supports the claim that ICs are maintained. Second, we show that actively using the stereotype to make predictions that are met with reward and punishment does not eliminate the bias. In addition, participants' operant reactions afford a novel online measure of ICs. In sum, our findings highlight the robustness of ICs that can be explained as a result of unbiased but noisy learning.

A transgenic resource for conditional competitive inhibition of conserved Drosophila microRNAs

PubMed Central

Fulga, Tudor A.; McNeill, Elizabeth M.; Binari, Richard; Yelick, Julia; Blanche, Alexandra; Booker, Matthew; Steinkraus, Bruno R.; Schnall-Levin, Michael; Zhao, Yong; DeLuca, Todd; Bejarano, Fernando; Han, Zhe; Lai, Eric C.; Wall, Dennis P.; Perrimon, Norbert; Van Vactor, David

2015-01-01

Although the impact of microRNAs (miRNAs) in development and disease is well established, understanding the function of individual miRNAs remains challenging. Development of competitive inhibitor molecules such as miRNA sponges has allowed the community to address individual miRNA function in vivo. However, the application of these loss-of-function strategies has been limited. Here we offer a comprehensive library of 141 conditional miRNA sponges targeting well-conserved miRNAs in Drosophila. Ubiquitous miRNA sponge delivery and consequent systemic miRNA inhibition uncovers a relatively small number of miRNA families underlying viability and gross morphogenesis, with false discovery rates in the 4–8% range. In contrast, tissue-specific silencing of muscle-enriched miRNAs reveals a surprisingly large number of novel miRNA contributions to the maintenance of adult indirect flight muscle structure and function. A strong correlation between miRNA abundance and physiological relevance is not observed, underscoring the importance of unbiased screens when assessing the contributions of miRNAs to complex biological processes. PMID:26081261

Metadynamics convergence law in a multidimensional system

NASA Astrophysics Data System (ADS)

Crespo, Yanier; Marinelli, Fabrizio; Pietrucci, Fabio; Laio, Alessandro

2010-05-01

Metadynamics is a powerful sampling technique that uses a nonequilibrium history-dependent process to reconstruct the free-energy surface as a function of the relevant collective variables s . In Bussi [Phys. Rev. Lett. 96, 090601 (2006)] it is proved that, in a Langevin process, metadynamics provides an unbiased estimate of the free energy F(s) . We here study the convergence properties of this approach in a multidimensional system, with a Hamiltonian depending on several variables. Specifically, we show that in a Monte Carlo metadynamics simulation of an Ising model the time average of the history-dependent potential converge to F(s) with the same law of an umbrella sampling performed in optimal conditions (i.e., with a bias exactly equal to the negative of the free energy). Remarkably, after a short transient, the error becomes approximately independent on the filling speed, showing that even in out-of-equilibrium conditions metadynamics allows recovering an accurate estimate of F(s) . These results have been obtained introducing a functional form of the history-dependent potential that avoids the onset of systematic errors near the boundaries of the free-energy landscape.

Metadynamics convergence law in a multidimensional system.

PubMed

Crespo, Yanier; Marinelli, Fabrizio; Pietrucci, Fabio; Laio, Alessandro

2010-05-01

Metadynamics is a powerful sampling technique that uses a nonequilibrium history-dependent process to reconstruct the free-energy surface as a function of the relevant collective variables s . In Bussi [Phys. Rev. Lett. 96, 090601 (2006)] it is proved that, in a Langevin process, metadynamics provides an unbiased estimate of the free energy F(s) . We here study the convergence properties of this approach in a multidimensional system, with a Hamiltonian depending on several variables. Specifically, we show that in a Monte Carlo metadynamics simulation of an Ising model the time average of the history-dependent potential converge to F(s) with the same law of an umbrella sampling performed in optimal conditions (i.e., with a bias exactly equal to the negative of the free energy). Remarkably, after a short transient, the error becomes approximately independent on the filling speed, showing that even in out-of-equilibrium conditions metadynamics allows recovering an accurate estimate of F(s) . These results have been obtained introducing a functional form of the history-dependent potential that avoids the onset of systematic errors near the boundaries of the free-energy landscape.

Comparison of algorithms to generate event times conditional on time-dependent covariates.

PubMed

Sylvestre, Marie-Pierre; Abrahamowicz, Michal

2008-06-30

The Cox proportional hazards model with time-dependent covariates (TDC) is now a part of the standard statistical analysis toolbox in medical research. As new methods involving more complex modeling of time-dependent variables are developed, simulations could often be used to systematically assess the performance of these models. Yet, generating event times conditional on TDC requires well-designed and efficient algorithms. We compare two classes of such algorithms: permutational algorithms (PAs) and algorithms based on a binomial model. We also propose a modification of the PA to incorporate a rejection sampler. We performed a simulation study to assess the accuracy, stability, and speed of these algorithms in several scenarios. Both classes of algorithms generated data sets that, once analyzed, provided virtually unbiased estimates with comparable variances. In terms of computational efficiency, the PA with the rejection sampler reduced the time necessary to generate data by more than 50 per cent relative to alternative methods. The PAs also allowed more flexibility in the specification of the marginal distributions of event times and required less calibration.

A multifaceted independent performance analysis of facial subspace recognition algorithms.

PubMed

Bajwa, Usama Ijaz; Taj, Imtiaz Ahmad; Anwar, Muhammad Waqas; Wang, Xuan

2013-01-01

Face recognition has emerged as the fastest growing biometric technology and has expanded a lot in the last few years. Many new algorithms and commercial systems have been proposed and developed. Most of them use Principal Component Analysis (PCA) as a base for their techniques. Different and even conflicting results have been reported by researchers comparing these algorithms. The purpose of this study is to have an independent comparative analysis considering both performance and computational complexity of six appearance based face recognition algorithms namely PCA, 2DPCA, A2DPCA, (2D)(2)PCA, LPP and 2DLPP under equal working conditions. This study was motivated due to the lack of unbiased comprehensive comparative analysis of some recent subspace methods with diverse distance metric combinations. For comparison with other studies, FERET, ORL and YALE databases have been used with evaluation criteria as of FERET evaluations which closely simulate real life scenarios. A comparison of results with previous studies is performed and anomalies are reported. An important contribution of this study is that it presents the suitable performance conditions for each of the algorithms under consideration.

Whole-Genome Sequencing Uncovers the Genetic Basis of Chronic Mountain Sickness in Andean Highlanders

PubMed Central

Zhou, Dan; Udpa, Nitin; Ronen, Roy; Stobdan, Tsering; Liang, Junbin; Appenzeller, Otto; Zhao, Huiwen W.; Yin, Yi; Du, Yuanping; Guo, Lixia; Cao, Rui; Wang, Yu; Jin, Xin; Huang, Chen; Jia, Wenlong; Cao, Dandan; Guo, Guangwu; Gamboa, Jorge L.; Villafuerte, Francisco; Callacondo, David; Xue, Jin; Liu, Siqi; Frazer, Kelly A.; Li, Yingrui; Bafna, Vineet; Haddad, Gabriel G.

2013-01-01

The hypoxic conditions at high altitudes present a challenge for survival, causing pressure for adaptation. Interestingly, many high-altitude denizens (particularly in the Andes) are maladapted, with a condition known as chronic mountain sickness (CMS) or Monge disease. To decode the genetic basis of this disease, we sequenced and compared the whole genomes of 20 Andean subjects (10 with CMS and 10 without). We discovered 11 regions genome-wide with significant differences in haplotype frequencies consistent with selective sweeps. In these regions, two genes (an erythropoiesis regulator, SENP1, and an oncogene, ANP32D) had a higher transcriptional response to hypoxia in individuals with CMS relative to those without. We further found that downregulating the orthologs of these genes in flies dramatically enhanced survival rates under hypoxia, demonstrating that suppression of SENP1 and ANP32D plays an essential role in hypoxia tolerance. Our study provides an unbiased framework to identify and validate the genetic basis of adaptation to high altitudes and identifies potentially targetable mechanisms for CMS treatment. PMID:23954164

Olfactory priming reinstates extinguished chocolate-induced conditioned place preference.

PubMed

La Mela, Immacolata; Latagliata, Emanuele Claudio; Patrono, Enrico; Puglisi-Allegra, Stefano; Ventura, Rossella

2010-02-01

A major problem in the dietary treatment of disorders associated with excessive eating, such as obesity, is the high rate of relapse into maladaptive eating habits after withdrawal from consumption of palatable, energy-dense food. As olfaction has a major role in appetite and eating behavior, in this study we used a reinstatement model based on conditioned place preference to investigate the ability of olfactory priming to reinstate extinguished chocolate-induced conditioned place preference in sated mice. We found that olfactory priming, which was ineffective in inducing conditioned place preference in the control group, reactivated place preference following the extinction procedure in the experimental group. These results extend previous reports of the reinstatement of food seeking induced by pellet priming and, for the first time, show the possibility of using olfactory priming in an animal model of relapse. In light of the major role of olfactory inputs in appetite and of cues in relapse, the present results indicate that smell is an important factor to consider in the treatment of eating disorders. 2009 Elsevier Ltd. All rights reserved.

Termite testing continues

Treesearch

Terence L. Wagner; Joe Mulrooney; Chris Petereson

2002-01-01

The United States Department of Agriculture Forest Service's termiticide testing program provides unbiased efficacy data for product registration using standardized tests, sites and evaluation procedures. Virtually all termiticides undergo Forest Service tests prior to registration.

Engagement of the medical-technology sector with society.

PubMed

Williams, David; Edelman, Elazer R; Radisic, Milica; Laurencin, Cato; Untereker, Darrel

2017-04-12

The medical-technology sector must educate society in an unbiased rational way about the successes and benefits of biotechnology innovation. Copyright © 2017, American Association for the Advancement of Science.

Unbiased water and methanol maser surveys of NGC 1333

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lyo, A-Ran; Kim, Jongsoo; Byun, Do-Young

2014-11-01

We present the results of unbiased 22 GHz H{sub 2}O water and 44 GHz class I CH{sub 3}OH methanol maser surveys in the central 7' × 10' area of NGC 1333 and two additional mapping observations of a 22 GHz water maser in a ∼3' × 3' area of the IRAS4A region. In the 22 GHz water maser survey of NGC 1333 with a sensitivity of σ ∼ 0.3 Jy, we confirmed the detection of masers toward H{sub 2}O(B) in the region of HH 7-11 and IRAS4B. We also detected new water masers located ∼20'' away in the western directionmore » of IRAS4B or ∼25'' away in the southern direction of IRAS4A. We could not, however, find young stellar objects or molecular outflows associated with them. They showed two different velocity components of ∼0 and ∼16 km s{sup –1}, which are blue- and redshifted relative to the adopted systemic velocity of ∼7 km s{sup –1} for NGC 1333. They also showed time variabilities in both intensity and velocity from multi-epoch observations and an anti-correlation between the intensities of the blue- and redshifted velocity components. We suggest that the unidentified power source of these masers might be found in the earliest evolutionary stage of star formation, before the onset of molecular outflows. Finding this kind of water maser is only possible through an unbiased blind survey. In the 44 GHz methanol maser survey with a sensitivity of σ ∼ 0.5 Jy, we confirmed masers toward IRAS4A2 and the eastern shock region of IRAS2A. Both sources are also detected in 95 and 132 GHz methanol maser lines. In addition, we had new detections of methanol masers at 95 and 132 GHz toward IRAS4B. In terms of the isotropic luminosity, we detected methanol maser sources brighter than ∼5 × 10{sup 25} erg s{sup –1} from our unbiased survey.« less

Agmatine attenuates methamphetamine-induced conditioned place preference in rats.

PubMed

Thorn, David A; Winter, Jerrold C; Li, Jun-Xu

2012-04-05

The polyamine agmatine modulates a variety of behavioral effects including the abuse-related effects of opioids and has been proposed as a potential medication candidate for the treatment of opioid abuse. However, little is known of the effects of agmatine on the abuse-related effects of other drugs of abuse. This study examined the effects of agmatine on the rewarding effects of methamphetamine in rats using a conditioned place preference paradigm. Methamphetamine (0.1-1.0mg/kg) dose-dependently increased the time spent in methamphetamine-paired side (place preference). Agmatine, at doses that did not produce place preference or aversion (10-32mg/kg), significantly decreased the development of methamphetamine-induced place preference when agmatine was administered in combination with methamphetamine during place conditioning. Agmatine also significantly decreased the expression of methamphetamine-induced place preference when an acute injection of agmatine was given immediately before test session. These doses of agmatine do not alter the motor activity in rats, suggesting that the observed attenuation of methamphetamine-induced place preference was not due to general behavioral disruption. Together, these data suggests that agmatine attenuates the rewarding effects of methamphetamine and may be able to modulate the abuse liability of methamphetamine. Copyright © 2012 Elsevier B.V. All rights reserved.

Addressing the social determinants of health through the Alameda County, California, place matters policy initiative.

PubMed

Schaff, Katherine; Desautels, Alexandra; Flournoy, Rebecca; Carson, Keith; Drenick, Teresa; Fujii, Darlene; Lee, Anna; Luginbuhl, Jessica; Mena, Mona; Shrago, Amy; Siegel, Anita; Stahl, Robert; Watkins-Tartt, Kimi; Willow, Pam; Witt, Sandra; Woloshin, Diane; Yamashita, Brenda

2013-11-01

In Alameda County, California, significant health inequities by race/ethnicity, income, and place persist. Many of the county's low-income residents and residents of color live in communities that have faced historical and current disinvestment through public policies. This disinvestment affects community conditions such as access to economic opportunities, well-maintained and affordable housing, high-quality schools, healthy food, safe parks, and clean water and air. These community conditions greatly affect health. At the invitation of the Joint Center for Political and Economic Studies' national Place Matters initiative, Alameda County Supervisor Keith Carson's Office and the Alameda County Public Health Department launched Alameda County Place Matters, an initiative that addresses community conditions through local policy change. We describe the initiative's creation, activities, policy successes, and best practices.

A Novel Hepadnavirus Identified in an Immunocompromised Domestic Cat in Australia.

PubMed

Aghazadeh, Mahdis; Shi, Mang; Barrs, Vanessa R; McLuckie, Alicia J; Lindsay, Scott A; Jameson, Barbara; Hampson, Bronte; Holmes, Edward C; Beatty, Julia A

2018-05-17

High-throughput transcriptome sequencing allows for the unbiased detection of viruses in host tissues. The application of this technique to immunosuppressed animals facilitates the detection of viruses that might otherwise be excluded or contained in immunocompetent individuals. To identify potential viral pathogens infecting domestic cats we performed high-throughput transcriptome sequencing of tissues from cats infected with feline immunodeficiency virus (FIV). A novel member of the Hepadnaviridae , tentatively named domestic cat hepadnavirus, was discovered in a lymphoma sample and its complete 3187 bp genome characterized. Phylogenetic analysis placed the domestic cat hepadnavirus as a divergent member of mammalian orthohepadnaviruses that exhibits no close relationship to any other virus. DNA extracted from whole blood from pet cats was positive for the novel hepadnavirus by PCR in 6 of 60 (10%) FIV-infected cats and 2 of 63 (3.2%) FIV-uninfected cats. The higher prevalence of hepadnavirus viraemia detected in FIV-infected cats mirrors that seen in human immunodeficiency virus-infected humans coinfected with hepatitis B virus. In summary, we report the first hepadnavirus infection in a carnivore and the first in a companion animal. The natural history, epidemiology and pathogenic potential of domestic cat hepadnavirus merits additional investigation.

Quantum Inference on Bayesian Networks

NASA Astrophysics Data System (ADS)

Yoder, Theodore; Low, Guang Hao; Chuang, Isaac

2014-03-01

Because quantum physics is naturally probabilistic, it seems reasonable to expect physical systems to describe probabilities and their evolution in a natural fashion. Here, we use quantum computation to speedup sampling from a graphical probability model, the Bayesian network. A specialization of this sampling problem is approximate Bayesian inference, where the distribution on query variables is sampled given the values e of evidence variables. Inference is a key part of modern machine learning and artificial intelligence tasks, but is known to be NP-hard. Classically, a single unbiased sample is obtained from a Bayesian network on n variables with at most m parents per node in time (nmP(e) - 1 / 2) , depending critically on P(e) , the probability the evidence might occur in the first place. However, by implementing a quantum version of rejection sampling, we obtain a square-root speedup, taking (n2m P(e) -1/2) time per sample. The speedup is the result of amplitude amplification, which is proving to be broadly applicable in sampling and machine learning tasks. In particular, we provide an explicit and efficient circuit construction that implements the algorithm without the need for oracle access.

FALCON: fast and unbiased reconstruction of high-density super-resolution microscopy data

NASA Astrophysics Data System (ADS)

Min, Junhong; Vonesch, Cédric; Kirshner, Hagai; Carlini, Lina; Olivier, Nicolas; Holden, Seamus; Manley, Suliana; Ye, Jong Chul; Unser, Michael

2014-04-01

Super resolution microscopy such as STORM and (F)PALM is now a well known method for biological studies at the nanometer scale. However, conventional imaging schemes based on sparse activation of photo-switchable fluorescent probes have inherently slow temporal resolution which is a serious limitation when investigating live-cell dynamics. Here, we present an algorithm for high-density super-resolution microscopy which combines a sparsity-promoting formulation with a Taylor series approximation of the PSF. Our algorithm is designed to provide unbiased localization on continuous space and high recall rates for high-density imaging, and to have orders-of-magnitude shorter run times compared to previous high-density algorithms. We validated our algorithm on both simulated and experimental data, and demonstrated live-cell imaging with temporal resolution of 2.5 seconds by recovering fast ER dynamics.

FALCON: fast and unbiased reconstruction of high-density super-resolution microscopy data

PubMed Central

Min, Junhong; Vonesch, Cédric; Kirshner, Hagai; Carlini, Lina; Olivier, Nicolas; Holden, Seamus; Manley, Suliana; Ye, Jong Chul; Unser, Michael

2014-01-01

Super resolution microscopy such as STORM and (F)PALM is now a well known method for biological studies at the nanometer scale. However, conventional imaging schemes based on sparse activation of photo-switchable fluorescent probes have inherently slow temporal resolution which is a serious limitation when investigating live-cell dynamics. Here, we present an algorithm for high-density super-resolution microscopy which combines a sparsity-promoting formulation with a Taylor series approximation of the PSF. Our algorithm is designed to provide unbiased localization on continuous space and high recall rates for high-density imaging, and to have orders-of-magnitude shorter run times compared to previous high-density algorithms. We validated our algorithm on both simulated and experimental data, and demonstrated live-cell imaging with temporal resolution of 2.5 seconds by recovering fast ER dynamics. PMID:24694686

Personalized recommendation based on unbiased consistence

NASA Astrophysics Data System (ADS)

Zhu, Xuzhen; Tian, Hui; Zhang, Ping; Hu, Zheng; Zhou, Tao

2015-08-01

Recently, in physical dynamics, mass-diffusion-based recommendation algorithms on bipartite network provide an efficient solution by automatically pushing possible relevant items to users according to their past preferences. However, traditional mass-diffusion-based algorithms just focus on unidirectional mass diffusion from objects having been collected to those which should be recommended, resulting in a biased causal similarity estimation and not-so-good performance. In this letter, we argue that in many cases, a user's interests are stable, and thus bidirectional mass diffusion abilities, no matter originated from objects having been collected or from those which should be recommended, should be consistently powerful, showing unbiased consistence. We further propose a consistence-based mass diffusion algorithm via bidirectional diffusion against biased causality, outperforming the state-of-the-art recommendation algorithms in disparate real data sets, including Netflix, MovieLens, Amazon and Rate Your Music.

A Fine Line: Ethical Issues Facing Childbirth Educators Negotiating Evidence, Beliefs, and Experience

PubMed Central

Morton, Christine H

2009-01-01

The trend toward evidence-based information in childbirth education has been ongoing for some time. Lamaze educators are encouraged to present evidence for the Six Care Practices That Support Normal Birth to pregnant women in their childbirth classes. In a previous article published in The Journal of Perinatal Education, my colleague and I provided an overview of the dilemmas facing American childbirth educators. Childbirth education is a domain in which many types of authoritative knowledge are used: evidence, beliefs, and experience. In our study, educators told us their goal is to provide class participants with unbiased information that allows women to choose what is best for them. In this article, I further analyze educators’ dilemmas and challenges in presenting unbiased information, and I discuss some ethical considerations in educators’ practices. PMID:19436597

Host Galaxy Properties Of The Swift Bat Hard X-ray Survey Of Agn

NASA Astrophysics Data System (ADS)

Koss, Michael; Mushotzky, R.; Veilleux, S.; Winter, L.

2010-03-01

Surveys of AGN taken in the optical, UV, and soft X-rays miss an important population of obscured AGN only visible in the hard X-rays and mid-IR wavelengths. The SWIFT BAT survey in the hard X-ray range (14-195 keV) has provided a uniquely unbiased sample of AGN unaffected by galactic or circumnuclear absorption. Optical imaging of this unbiased sample provides a new opportunity to understand how the environments of the host galaxies are linked to AGN. In 2008, we observed 90 of these targets at Kitt Peak with the 2.1m in the SDSS ugriz bands over 17 nights. Using these observations and SDSS data we review the relationships between color, morphology, merger activity, stellar mass, star formation, and AGN luminosity for a sample of 145 AGN Hard X-ray Selected AGN.

An unbiased X-ray sampling of stars within 25 parsecs of the Sun

NASA Technical Reports Server (NTRS)

Johnson, H. M.

1985-01-01

A search of all of the Einstein Observatory IPC and HRI fields for untargeted stars in the Woolley, et al., Catalogue of the nearby stars is reported. Optical data and IPC coordinates, flux density F sub x, and luminosity L sub x, or upper limits, are tabulated for 126 single or blended systems, and HRI results for a few of them. IPC luminosity functions are derived for the systems, for 193 individual stars in the systems (with L sub x shared equally among blended components), and for 63 individual M dwarfs. These stars have relatively large X-ray flux densities that are free of interstellar extinction, because they are nearby, but they are otherwise unbiased with respect to the X-ray properties that are found in a defined small space around the Sun.

Biased and unbiased strategies to identify biologically active small molecules.

PubMed

Abet, Valentina; Mariani, Angelica; Truscott, Fiona R; Britton, Sébastien; Rodriguez, Raphaël

2014-08-15

Small molecules are central players in chemical biology studies. They promote the perturbation of cellular processes underlying diseases and enable the identification of biological targets that can be validated for therapeutic intervention. Small molecules have been shown to accurately tune a single function of pluripotent proteins in a reversible manner with exceptional temporal resolution. The identification of molecular probes and drugs remains a worthy challenge that can be addressed by the use of biased and unbiased strategies. Hypothesis-driven methodologies employs a known biological target to synthesize complementary hits while discovery-driven strategies offer the additional means of identifying previously unanticipated biological targets. This review article provides a general overview of recent synthetic frameworks that gave rise to an impressive arsenal of biologically active small molecules with unprecedented cellular mechanisms. Copyright © 2014. Published by Elsevier Ltd.

Epidemiologic Evaluation of Measurement Data in the Presence of Detection Limits

PubMed Central

Lubin, Jay H.; Colt, Joanne S.; Camann, David; Davis, Scott; Cerhan, James R.; Severson, Richard K.; Bernstein, Leslie; Hartge, Patricia

2004-01-01

Quantitative measurements of environmental factors greatly improve the quality of epidemiologic studies but can pose challenges because of the presence of upper or lower detection limits or interfering compounds, which do not allow for precise measured values. We consider the regression of an environmental measurement (dependent variable) on several covariates (independent variables). Various strategies are commonly employed to impute values for interval-measured data, including assignment of one-half the detection limit to nondetected values or of “fill-in” values randomly selected from an appropriate distribution. On the basis of a limited simulation study, we found that the former approach can be biased unless the percentage of measurements below detection limits is small (5–10%). The fill-in approach generally produces unbiased parameter estimates but may produce biased variance estimates and thereby distort inference when 30% or more of the data are below detection limits. Truncated data methods (e.g., Tobit regression) and multiple imputation offer two unbiased approaches for analyzing measurement data with detection limits. If interest resides solely on regression parameters, then Tobit regression can be used. If individualized values for measurements below detection limits are needed for additional analysis, such as relative risk regression or graphical display, then multiple imputation produces unbiased estimates and nominal confidence intervals unless the proportion of missing data is extreme. We illustrate various approaches using measurements of pesticide residues in carpet dust in control subjects from a case–control study of non-Hodgkin lymphoma. PMID:15579415

Missing continuous outcomes under covariate dependent missingness in cluster randomised trials

PubMed Central

Diaz-Ordaz, Karla; Bartlett, Jonathan W

2016-01-01

Attrition is a common occurrence in cluster randomised trials which leads to missing outcome data. Two approaches for analysing such trials are cluster-level analysis and individual-level analysis. This paper compares the performance of unadjusted cluster-level analysis, baseline covariate adjusted cluster-level analysis and linear mixed model analysis, under baseline covariate dependent missingness in continuous outcomes, in terms of bias, average estimated standard error and coverage probability. The methods of complete records analysis and multiple imputation are used to handle the missing outcome data. We considered four scenarios, with the missingness mechanism and baseline covariate effect on outcome either the same or different between intervention groups. We show that both unadjusted cluster-level analysis and baseline covariate adjusted cluster-level analysis give unbiased estimates of the intervention effect only if both intervention groups have the same missingness mechanisms and there is no interaction between baseline covariate and intervention group. Linear mixed model and multiple imputation give unbiased estimates under all four considered scenarios, provided that an interaction of intervention and baseline covariate is included in the model when appropriate. Cluster mean imputation has been proposed as a valid approach for handling missing outcomes in cluster randomised trials. We show that cluster mean imputation only gives unbiased estimates when missingness mechanism is the same between the intervention groups and there is no interaction between baseline covariate and intervention group. Multiple imputation shows overcoverage for small number of clusters in each intervention group. PMID:27177885

NullSeq: A Tool for Generating Random Coding Sequences with Desired Amino Acid and GC Contents.

PubMed

Liu, Sophia S; Hockenberry, Adam J; Lancichinetti, Andrea; Jewett, Michael C; Amaral, Luís A N

2016-11-01

The existence of over- and under-represented sequence motifs in genomes provides evidence of selective evolutionary pressures on biological mechanisms such as transcription, translation, ligand-substrate binding, and host immunity. In order to accurately identify motifs and other genome-scale patterns of interest, it is essential to be able to generate accurate null models that are appropriate for the sequences under study. While many tools have been developed to create random nucleotide sequences, protein coding sequences are subject to a unique set of constraints that complicates the process of generating appropriate null models. There are currently no tools available that allow users to create random coding sequences with specified amino acid composition and GC content for the purpose of hypothesis testing. Using the principle of maximum entropy, we developed a method that generates unbiased random sequences with pre-specified amino acid and GC content, which we have developed into a python package. Our method is the simplest way to obtain maximally unbiased random sequences that are subject to GC usage and primary amino acid sequence constraints. Furthermore, this approach can easily be expanded to create unbiased random sequences that incorporate more complicated constraints such as individual nucleotide usage or even di-nucleotide frequencies. The ability to generate correctly specified null models will allow researchers to accurately identify sequence motifs which will lead to a better understanding of biological processes as well as more effective engineering of biological systems.

Self-aligned blocking integration demonstration for critical sub-30nm pitch Mx level patterning with EUV self-aligned double patterning

NASA Astrophysics Data System (ADS)

Raley, Angélique; Lee, Joe; Smith, Jeffrey T.; Sun, Xinghua; Farrell, Richard A.; Shearer, Jeffrey; Xu, Yongan; Ko, Akiteru; Metz, Andrew W.; Biolsi, Peter; Devilliers, Anton; Arnold, John; Felix, Nelson

2018-04-01

We report a sub-30nm pitch self-aligned double patterning (SADP) integration scheme with EUV lithography coupled with self-aligned block technology (SAB) targeting the back end of line (BEOL) metal line patterning applications for logic nodes beyond 5nm. The integration demonstration is a validation of the scalability of a previously reported flow, which used 193nm immersion SADP targeting a 40nm pitch with the same material sets (Si3N4 mandrel, SiO2 spacer, Spin on carbon, spin on glass). The multi-color integration approach is successfully demonstrated and provides a valuable method to address overlay concerns and more generally edge placement error (EPE) as a whole for advanced process nodes. Unbiased LER/LWR analysis comparison between EUV SADP and 193nm immersion SADP shows that both integrations follow the same trend throughout the process steps. While EUV SADP shows increased LER after mandrel pull, metal hardmask open and dielectric etch compared to 193nm immersion SADP, the final process performance is matched in terms of LWR (1.08nm 3 sigma unbiased) and is only 6% higher than 193nm immersion SADP for average unbiased LER. Using EUV SADP enables almost doubling the line density while keeping most of the remaining processes and films unchanged, and provides a compelling alternative to other multipatterning integrations, which present their own sets of challenges.

Missing continuous outcomes under covariate dependent missingness in cluster randomised trials.

PubMed

Hossain, Anower; Diaz-Ordaz, Karla; Bartlett, Jonathan W

2017-06-01

Attrition is a common occurrence in cluster randomised trials which leads to missing outcome data. Two approaches for analysing such trials are cluster-level analysis and individual-level analysis. This paper compares the performance of unadjusted cluster-level analysis, baseline covariate adjusted cluster-level analysis and linear mixed model analysis, under baseline covariate dependent missingness in continuous outcomes, in terms of bias, average estimated standard error and coverage probability. The methods of complete records analysis and multiple imputation are used to handle the missing outcome data. We considered four scenarios, with the missingness mechanism and baseline covariate effect on outcome either the same or different between intervention groups. We show that both unadjusted cluster-level analysis and baseline covariate adjusted cluster-level analysis give unbiased estimates of the intervention effect only if both intervention groups have the same missingness mechanisms and there is no interaction between baseline covariate and intervention group. Linear mixed model and multiple imputation give unbiased estimates under all four considered scenarios, provided that an interaction of intervention and baseline covariate is included in the model when appropriate. Cluster mean imputation has been proposed as a valid approach for handling missing outcomes in cluster randomised trials. We show that cluster mean imputation only gives unbiased estimates when missingness mechanism is the same between the intervention groups and there is no interaction between baseline covariate and intervention group. Multiple imputation shows overcoverage for small number of clusters in each intervention group.

Testing assumptions for unbiased estimation of survival of radiomarked harlequin ducks

USGS Publications Warehouse

Esler, Daniel N.; Mulcahy, Daniel M.; Jarvis, Robert L.

2000-01-01

Unbiased estimates of survival based on individuals outfitted with radiotransmitters require meeting the assumptions that radios do not affect survival, and animals for which the radio signal is lost have the same survival probability as those for which fate is known. In most survival studies, researchers have made these assumptions without testing their validity. We tested these assumptions by comparing interannual recapture rates (and, by inference, survival) between radioed and unradioed adult female harlequin ducks (Histrionicus histrionicus), and for radioed females, between right-censored birds (i.e., those for which the radio signal was lost during the telemetry monitoring period) and birds with known fates. We found that recapture rates of birds equipped with implanted radiotransmitters (21.6 ± 3.0%; x̄ ± SE) were similar to unradioed birds (21.7 ± 8.6%), suggesting that radios did not affect survival. Recapture rates also were similar between right-censored (20.6 ± 5.1%) and known-fate individuals (22.1 ± 3.8%), suggesting that missing birds were not subject to differential mortality. We also determined that capture and handling resulted in short-term loss of body mass for both radioed and unradioed females and that this effect was more pronounced for radioed birds (the difference between groups was 15.4 ± 7.1 g). However, no difference existed in body mass after recapture 1 year later. Our study suggests that implanted radios are an unbiased method for estimating survival of harlequin ducks and likely other species under similar circumstances.

Evaluation and construction of diagnostic criteria for inclusion body myositis

PubMed Central

Mammen, Andrew L.; Amato, Anthony A.; Weiss, Michael D.; Needham, Merrilee

2014-01-01

Objective: To use patient data to evaluate and construct diagnostic criteria for inclusion body myositis (IBM), a progressive disease of skeletal muscle. Methods: The literature was reviewed to identify all previously proposed IBM diagnostic criteria. These criteria were applied through medical records review to 200 patients diagnosed as having IBM and 171 patients diagnosed as having a muscle disease other than IBM by neuromuscular specialists at 2 institutions, and to a validating set of 66 additional patients with IBM from 2 other institutions. Machine learning techniques were used for unbiased construction of diagnostic criteria. Results: Twenty-four previously proposed IBM diagnostic categories were identified. Twelve categories all performed with high (≥97%) specificity but varied substantially in their sensitivities (11%–84%). The best performing category was European Neuromuscular Centre 2013 probable (sensitivity of 84%). Specialized pathologic features and newly introduced strength criteria (comparative knee extension/hip flexion strength) performed poorly. Unbiased data-directed analysis of 20 features in 371 patients resulted in construction of higher-performing data-derived diagnostic criteria (90% sensitivity and 96% specificity). Conclusions: Published expert consensus–derived IBM diagnostic categories have uniformly high specificity but wide-ranging sensitivities. High-performing IBM diagnostic category criteria can be developed directly from principled unbiased analysis of patient data. Classification of evidence: This study provides Class II evidence that published expert consensus–derived IBM diagnostic categories accurately distinguish IBM from other muscle disease with high specificity but wide-ranging sensitivities. PMID:24975859

AN UNBIASED 1.3 mm EMISSION LINE SURVEY OF THE PROTOPLANETARY DISK ORBITING LkCa 15

DOE Office of Scientific and Technical Information (OSTI.GOV)

Punzi, K. M.; Kastner, J. H.; Hily-Blant, P.

2015-06-01

The outer (>30 AU) regions of the dusty circumstellar disk orbiting the ∼2–5 Myr old, actively accreting solar analog LkCa 15 are known to be chemically rich, and the inner disk may host a young protoplanet within its central cavity. To obtain a complete census of the brightest molecular line emission emanating from the LkCa 15 disk over the 210–270 GHz (1.4–1.1 mm) range, we have conducted an unbiased radio spectroscopic survey with the Institute de Radioastronomie Millimétrique (IRAM) 30 m telescope. The survey demonstrates that in this spectral region, the most readily detectable lines are those of CO andmore » its isotopologues {sup 13}CO and C{sup 18}O, as well as HCO{sup +}, HCN, CN, C{sub 2}H, CS, and H{sub 2}CO. All of these species had been previously detected in the LkCa 15 disk; however, the present survey includes the first complete coverage of the CN (2–1) and C{sub 2}H (3–2) hyperfine complexes. Modeling of these emission complexes indicates that the CN and C{sub 2}H either reside in the coldest regions of the disk or are subthermally excited, and that their abundances are enhanced relative to molecular clouds and young stellar object environments. These results highlight the value of unbiased single-dish line surveys in guiding future high-resolution interferometric imaging of disks.« less

Prolyl-4-hydroxylase domain 3 (PHD3) is a critical terminator for cell survival of macrophages under stress conditions.

PubMed

Swain, Lija; Wottawa, Marieke; Hillemann, Annette; Beneke, Angelika; Odagiri, Haruki; Terada, Kazutoyo; Endo, Motoyoshi; Oike, Yuichi; Farhat, Katja; Katschinski, Dörthe M

2014-09-01

On a molecular level, cells sense changes in oxygen availability through the PHDs, which regulate the protein stability of the α-subunit of the transcription factor HIF. Especially, PHD3 has been additionally associated with apoptotic cell death. We hypothesized that PHD3 plays a role in cell-fate decisions in macrophages. Therefore, myeloid-specific PHD3(-/-) mice were created and analyzed. PHD3(-/-) BMDM showed no altered HIF-1α or HIF-2α stabilization or increased HIF target gene expression in normoxia or hypoxia. Macrophage M1 and M2 polarization was unchanged likewise. Compared with macrophages from WT littermates, PHD3(-/-) BMDM exhibited a significant reduction in TUNEL-positive cells after serum withdrawal or treatment with stauro and SNAP. Under the same conditions, PHD3(-/-) BMDM also showed less Annexin V staining, which is representative for membrane disruption, and indicated a reduced early apoptosis. In an unbiased transcriptome screen, we found that Angptl2 expression was reduced in PHD3(-/-) BMDM under stress conditions. Addition of rAngptl2 rescued the antiapoptotic phenotype, demonstrating that it is involved in the PHD3-mediated response toward apoptotic stimuli in macrophages. © 2014 Society for Leukocyte Biology.

Altered methamphetamine place conditioning in mice vaccinated with a succinyl-methamphetamine-tetanus-toxoid vaccine.

PubMed

Haile, Colin N; Kosten, Therese A; Shen, Xiaoyun Y; O'Malley, Patrick W; Winoske, Kevin J; Kinsey, Berma M; Wu, Yan; Huang, Zhen; Lykissa, Ernest D; Naidu, Naga; Cox, Joseph A; Arora, Reetakshi; Kosten, Thomas R; Orson, Frank M

2015-12-01

We previously reported that an anti-methamphetamine (MA) vaccine attenuated drug-conditioned effects in mice, but it used a carrier protein and adjuvant not available for clinical use. Here we produced a vaccine with the same hapten (succinyl-methamphetamine, SMA) but attached to tetanus toxoid (SMA-TT) and adsorbed to aluminum hydroxide, components approved for use in humans. We then assessed the vaccine's ability to generate anti-MA antibodies, alter acquisition and reinstatement of MA place conditioning, and prevent MA brain penetration. Mice were administered SMA-TT at weeks 0 and 3 and non-vaccinated mice received saline. Anti-MA antibody concentrations were determined at 8 and 12 weeks. Place conditioning began during week 9 in which vaccinated and non-vaccinated mice were divided into groups and conditioned with .5, or 2.0 mg/kg MA. Following acquisition training, mice were extinguished and then a reinstatement test was performed in which mice were administered their original training dose of MA. Separate groups of non-vaccinated and vaccinated mice were administered .5 and 2.0 mg/kg MA and brain MA levels determined. Anti-MA antibody levels were elevated at week 8 and remained so through week 12. The SMA-TT vaccine attenuated acquisition and reinstatement of MA place conditioning. Significantly greater proportions of vaccinated mice during acquisition and reinstatement tests showed conditioned place aversion. Moreover, MA brain levels were decreased in vaccinated mice following administration of both doses of MA. Results support further development of anti-MA vaccines using components approved for use in humans. © American Academy of Addiction Psychiatry.

[Central Work Camp in Jaworzno (1945-1949) -- epidemiological aspects -- attempt of evaluation].

PubMed

Smolik, Przemysław

2013-01-01

Publication presents the short history of camp hospital which was organised in 1943 Nazi concentration camp Neu-Dachs in Jaworzno. The camp was a branch of Oświecim concentration camp. Atfer the war damage of the camp, the restoration was begun in 1945. Already in Febraury 1945, in place of German concentration camp, rises Central Work Camp. Several thousands of prisoners of war were placed there. The prisoners of war: Germans, Volksdeutches, Silesians were forced emlpoyed in nearby coal mines. Since 1947 the camp was a place of staying for several thousands Ukrainians who were displaced from eastern part of Poland in "Vistula Operation". Based on available written materials, publication is an attempt to analyse and evaluate: sanitary conditions, prison illnesses, mortality reasons among prisoners, hospital equipment, personel work conditions. The publication gives opportunity to compare conditions of prison hospital under nazi occupation and conditions in the camp which was organised in the same place under Stalin system of terror.

The influence of place attachment and experience use history on perceived depreciative visitor behavior and crowding in an urban national park.

PubMed

Eder, Renate; Arnberger, Arne

2012-10-01

Research on recreational place attachment suggests that place identity, or the emotional/symbolic ties people have to places, and place dependence, which describes a functional attachment to a specific place, influence the perception of social and environmental site conditions. Recent research, however, has found that place attachment is not always a predictor of such perceptions. This study investigated the influence of place attachment and experience use history on the perception of depreciative visitor behavior, recreation impacts and crowding in an urban national park. In 2006, 605 on-site visitors to the heavily-used Viennese part of the Danube Floodplains National Park were asked about past experience, place attachment, perceptions of depreciative visitor behavior, crowding, changes in visitor numbers during the past ten years, and recreation impacts on wildlife. Confirmatory factor analysis confirmed the two dimensions of place attachment. Linear regression analyses found that place identity and place dependence were related to some perceived depreciative visitor behaviors and visitor number changes but not to crowding, while experience use history additionally related to perceived crowding. Visitors with higher place attachment and past experience were more sensitive to social and environmental site conditions. Management implications of the findings are discussed.

Addressing the Social Determinants of Health through the Alameda County, California, Place Matters Policy Initiative

PubMed Central

Schaff, Katherine; Flournoy, Rebecca; Carson, Keith; Drenick, Teresa; Fujii, Darlene; Lee, Anna; Luginbuhl, Jessica; Mena, Mona; Shrago, Amy; Siegel, Anita; Stahl, Robert; Watkins-Tartt, Kimi; Willow, Pam; Witt, Sandra; Woloshin, Diane; Yamashita, Brenda

2013-01-01

In Alameda County, California, significant health inequities by race/ethnicity, income, and place persist. Many of the county's low-income residents and residents of color live in communities that have faced historical and current disinvestment through public policies. This disinvestment affects community conditions such as access to economic opportunities, well-maintained and affordable housing, high-quality schools, healthy food, safe parks, and clean water and air. These community conditions greatly affect health. At the invitation of the Joint Center for Political and Economic Studies' national Place Matters initiative, Alameda County Supervisor Keith Carson's Office and the Alameda County Public Health Department launched Alameda County Place Matters, an initiative that addresses community conditions through local policy change. We describe the initiative's creation, activities, policy successes, and best practices. PMID:24179279

48 CFR 31.201-6 - Accounting for unallowable costs.

Code of Federal Regulations, 2012 CFR

2012-10-01

... unbiased sample that is a reasonable representation of the sampling universe. (ii) Any large dollar value... universe from that sampled cost is also subject to the same penalty provisions. (4) Use of statistical...

48 CFR 31.201-6 - Accounting for unallowable costs.

Code of Federal Regulations, 2013 CFR

2013-10-01

... unbiased sample that is a reasonable representation of the sampling universe. (ii) Any large dollar value... universe from that sampled cost is also subject to the same penalty provisions. (4) Use of statistical...

48 CFR 31.201-6 - Accounting for unallowable costs.

Code of Federal Regulations, 2014 CFR

2014-10-01

... unbiased sample that is a reasonable representation of the sampling universe. (ii) Any large dollar value... universe from that sampled cost is also subject to the same penalty provisions. (4) Use of statistical...

48 CFR 31.201-6 - Accounting for unallowable costs.

Code of Federal Regulations, 2011 CFR

2011-10-01

... unbiased sample that is a reasonable representation of the sampling universe. (ii) Any large dollar value... universe from that sampled cost is also subject to the same penalty provisions. (4) Use of statistical...

78 FR 65974 - Atlantic Highly Migratory Species; Advisory Panel for Atlantic Highly Migratory Species Southeast...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-04

... HMS stock assessment. In order to ensure that the peer review is unbiased, individuals who... fisheries, related industries, research, teaching, writing, conservation, or management of marine organisms...

48 CFR 25.703-1 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-10-01

... that is to be used specifically— (i) To restrict the free flow of unbiased information in Iran; or (ii) To disrupt, monitor, or otherwise restrict speech of the people of Iran; and (2) Does not include...

Is Science Biased Toward Natural?

EPA Science Inventory

Having widely available, accurate, understandable, and unbiased scientific information is central to the successful resolution of the typically contentious, divisive, and litigious natural resource policy issue. Three examples are offered to illustrate how science is often misus...

Jensen's Last Stand.

ERIC Educational Resources Information Center

Gould, Stephen Jay

1980-01-01

Challenges Jensen's arguments (set forth in the book "Bias in Mental Testing") that intelligence tests are scientifically unbiased and that IQ and other mental tests measure something called "intelligence" by refuting Jensen's reading of the psychometric research literature. (EF)

Unexpected Ground-State Structure and Mechanical Properties of Ir₂Zr Intermetallic Compound.

PubMed

Zhang, Meiguang; Cao, Rui; Zhao, Meijie; Du, Juan; Cheng, Ke

2018-01-10

Using an unbiased structure searching method, a new orthorhombic Cmmm structure consisting of ZrIr 12 polyhedron building blocks is predicted to be the thermodynamic ground-state of stoichiometric intermetallic Ir₂Zr in Ir-Zr systems. The formation enthalpy of the Cmmm structure is considerably lower than that of the previously synthesized Cu₂Mg-type phase, by ~107 meV/atom, as demonstrated by the calculation of formation enthalpy. Meanwhile, the phonon dispersion calculations further confirmed the dynamical stability of Cmmm phase under ambient conditions. The mechanical properties, including elastic stability, rigidity, and incompressibility, as well as the elastic anisotropy of Cmmm -Ir₂Zr intermetallic, have thus been fully determined. It is found that the predicted Cmmm phase exhibits nearly elastic isotropic and great resistance to shear deformations within the (100) crystal plane. Evidence of atomic bonding related to the structural stability for Ir₂Zr were manifested by calculations of the electronic structures.

Priming in implicit memory tasks: prior study causes enhanced discriminability, not only bias.

PubMed

Zeelenberg, René; Wagenmakers, Eric-Jan M; Raaijmakers, Jeroen G W

2002-03-01

R. Ratcliff and G. McKoon (1995, 1996, 1997; R. Ratcliff, D. Allbritton, & G. McKoon, 1997) have argued that repetition priming effects are solely due to bias. They showed that prior study of the target resulted in a benefit in a later implicit memory task. However, prior study of a stimulus similar to the target resulted in a cost. The present study, using a 2-alternative forced-choice procedure, investigated the effect of prior study in an unbiased condition: Both alternatives were studied prior to their presentation in an implicit memory task. Contrary to a pure bias interpretation of priming, consistent evidence was obtained in 3 implicit memory tasks (word fragment completion, auditory word identification, and picture identification) that performance was better when both alternatives were studied than when neither alternative was studied. These results show that prior study results in enhanced discriminability, not only bias.

Carbon storage in US wetlands

PubMed Central

Nahlik, A. M.; Fennessy, M. S.

2016-01-01

Wetland soils contain some of the highest stores of soil carbon in the biosphere. However, there is little understanding of the quantity and distribution of carbon stored in our remaining wetlands or of the potential effects of human disturbance on these stocks. Here we use field data from the 2011 National Wetland Condition Assessment to provide unbiased estimates of soil carbon stocks for wetlands at regional and national scales. We find that wetlands in the conterminous United States store a total of 11.52 PgC, much of which is within soils deeper than 30 cm. Freshwater inland wetlands, in part due to their substantial areal extent, hold nearly ten-fold more carbon than tidal saltwater sites—indicating their importance in regional carbon storage. Our data suggest a possible relationship between carbon stocks and anthropogenic disturbance. These data highlight the need to protect wetlands to mitigate the risk of avoidable contributions to climate change. PMID:27958272

Battery testing at Argonne National Laboratory

NASA Astrophysics Data System (ADS)

Deluca, W. H.; Gillie, K. R.; Kulaga, J. E.; Smaga, J. A.; Tummillo, A. F.; Webster, C. E.

1993-03-01

Argonne National Laboratory's Analysis & Diagnostic Laboratory (ADL) tests advanced batteries under simulated electric and hybrid vehicle operating conditions. The ADL facilities also include a post-test analysis laboratory to determine, in a protected atmosphere if needed, component compositional changes and failure mechanisms. The ADL provides a common basis for battery performance characterization and life evaluations with unbiased application of tests and analyses. The battery evaluations and post-test examinations help identify factors that limit system performance and life and the most-promising R&D approaches for overcoming these limitations. Since 1991, performance characterizations and/or life evaluations have been conducted on eight battery technologies: Na/S, Li/S, Zn/Br, Ni/MH, Ni/Zn, Ni/Cd, Ni/Fe, and lead-acid. These evaluations were performed for the Department of Energy's. Office of Transportation Technologies, Electric and Hybrid Propulsion Division (DOE/OTT/EHP), and Electric Power Research Institute (EPRI) Transportation Program. The results obtained are discussed.

Nine-channel wavelength tunable single mode laser array based on slots.

PubMed

Guo, Wei-Hua; Lu, Qiaoyin; Nawrocka, Marta; Abdullaev, Azat; O'Callaghan, James; Donegan, John F

2013-04-22

A 9-channel wavelength tunable single-mode laser array based on slots is presented. The fabricated laser array demonstrated a threshold current in a range of 19~21 mA with the SOA unbiased at 20°C under continuous wave condition. Stable single mode performances have been observed with side-mode suppression-ratio (SMSR) > 50 dB. The output power higher than 37 mW was obtained at the SOA injected current of 70 mA for all the 9 channels within the laser array. A wavelength quasi-continuous tuning range of about 27 nm has been achieved for the laser array with the temperature variations from 10°C to 45°C. This array platform is of a single growth and monolithically integrable. It can be easily fabricated by standard photolithography. In addition, it potentially removes the yield problem due to the uncertainty of the facet cleaving.

Multivariate normal maximum likelihood with both ordinal and continuous variables, and data missing at random.

PubMed

Pritikin, Joshua N; Brick, Timothy R; Neale, Michael C

2018-04-01

A novel method for the maximum likelihood estimation of structural equation models (SEM) with both ordinal and continuous indicators is introduced using a flexible multivariate probit model for the ordinal indicators. A full information approach ensures unbiased estimates for data missing at random. Exceeding the capability of prior methods, up to 13 ordinal variables can be included before integration time increases beyond 1 s per row. The method relies on the axiom of conditional probability to split apart the distribution of continuous and ordinal variables. Due to the symmetry of the axiom, two similar methods are available. A simulation study provides evidence that the two similar approaches offer equal accuracy. A further simulation is used to develop a heuristic to automatically select the most computationally efficient approach. Joint ordinal continuous SEM is implemented in OpenMx, free and open-source software.

Shield evaluation and performance testing at the USMB`s Strategic Structures Testing Laboratory

DOE Office of Scientific and Technical Information (OSTI.GOV)

Barczak, T.M.; Gearhart, D.F.

1996-12-31

Historically, shield performance testing is conducted by the support manufacturers at European facilities. The U.S. Bureau of Mines (USBM) has conducted extensive research in shield Mechanics and is now opening its Strategic Structures Testing (SST) Laboratory to the mining industry for shield performance testing. The SST Laboratory provides unique shield testing capabilities using the Mine Roof Simulator (MRS) load frame. The MRS provides realistic and cost-effective shield evaluation by combining both vertical and horizontal loading into a single load cycle; whereas, several load cycles would be required to obtain this loading in a static frame. In addition to these advantages,more » the USBM acts as an independent research organization to provide an unbiased assessment of shield performance. This paper describes the USBM`s shield testing program that is designed specifically to simulate in-service mining conditions using the unique the capabilities of the SST Laboratory.« less

Carbon storage in US wetlands

NASA Astrophysics Data System (ADS)

Nahlik, A. M.; Fennessy, M. S.

2016-12-01

Wetland soils contain some of the highest stores of soil carbon in the biosphere. However, there is little understanding of the quantity and distribution of carbon stored in our remaining wetlands or of the potential effects of human disturbance on these stocks. Here we use field data from the 2011 National Wetland Condition Assessment to provide unbiased estimates of soil carbon stocks for wetlands at regional and national scales. We find that wetlands in the conterminous United States store a total of 11.52 PgC, much of which is within soils deeper than 30 cm. Freshwater inland wetlands, in part due to their substantial areal extent, hold nearly ten-fold more carbon than tidal saltwater sites--indicating their importance in regional carbon storage. Our data suggest a possible relationship between carbon stocks and anthropogenic disturbance. These data highlight the need to protect wetlands to mitigate the risk of avoidable contributions to climate change.

Identification of a parametric, discrete-time model of ankle stiffness.

PubMed

Guarin, Diego L; Jalaleddini, Kian; Kearney, Robert E

2013-01-01

Dynamic ankle joint stiffness defines the relationship between the position of the ankle and the torque acting about it and can be separated into intrinsic and reflex components. Under stationary conditions, intrinsic stiffness can described by a linear second order system while reflex stiffness is described by Hammerstein system whose input is delayed velocity. Given that reflex and intrinsic torque cannot be measured separately, there has been much interest in the development of system identification techniques to separate them analytically. To date, most methods have been nonparametric and as a result there is no direct link between the estimated parameters and those of the stiffness model. This paper presents a novel algorithm for identification of a discrete-time model of ankle stiffness. Through simulations we show that the algorithm gives unbiased results even in the presence of large, non-white noise. Application of the method to experimental data demonstrates that it produces results consistent with previous findings.

Intersubject synchronization of cortical activity during natural vision.

PubMed

Hasson, Uri; Nir, Yuval; Levy, Ifat; Fuhrmann, Galit; Malach, Rafael

2004-03-12

To what extent do all brains work alike during natural conditions? We explored this question by letting five subjects freely view half an hour of a popular movie while undergoing functional brain imaging. Applying an unbiased analysis in which spatiotemporal activity patterns in one brain were used to "model" activity in another brain, we found a striking level of voxel-by-voxel synchronization between individuals, not only in primary and secondary visual and auditory areas but also in association cortices. The results reveal a surprising tendency of individual brains to "tick collectively" during natural vision. The intersubject synchronization consisted of a widespread cortical activation pattern correlated with emotionally arousing scenes and regionally selective components. The characteristics of these activations were revealed with the use of an open-ended "reverse-correlation" approach, which inverts the conventional analysis by letting the brain signals themselves "pick up" the optimal stimuli for each specialized cortical area.

Correlated Coulomb Drag in Capacitively Coupled Quantum-Dot Structures.

PubMed

Kaasbjerg, Kristen; Jauho, Antti-Pekka

2016-05-13

We study theoretically Coulomb drag in capacitively coupled quantum dots (CQDs)-a bias-driven dot coupled to an unbiased dot where transport is due to Coulomb mediated energy transfer drag. To this end, we introduce a master-equation approach that accounts for higher-order tunneling (cotunneling) processes as well as energy-dependent lead couplings, and identify a mesoscopic Coulomb drag mechanism driven by nonlocal multielectron cotunneling processes. Our theory establishes the conditions for a nonzero drag as well as the direction of the drag current in terms of microscopic system parameters. Interestingly, the direction of the drag current is not determined by the drive current, but by an interplay between the energy-dependent lead couplings. Studying the drag mechanism in a graphene-based CQD heterostructure, we show that the predictions of our theory are consistent with recent experiments on Coulomb drag in CQD systems.

Boundary Conditions for the Paleoenvironment: Chemical and Physical Processes in the Pre-Solar Nebula

NASA Technical Reports Server (NTRS)

Irvine, William M.; Schloerb, F. Peter

1997-01-01

The basic theme of this program is the study of molecular complexity and evolution in interstellar clouds and in primitive solar system objects. Research has included the detection and study of a number of new interstellar molecules and investigation of reaction pathways for astrochemistry from a comparison of theory and observed molecular abundances. The latter includes studies of cold, dark clouds in which ion-molecule chemistry should predominate, searches for the effects of interchange of material between the gas and solid phases in interstellar clouds, unbiased spectral surveys of particular sources, and systematic investigation of the interlinked chemistry and physics of dense interstellar clouds. In addition, the study of comets has allowed a comparison between the chemistry of such minimally thermally processed objects and that of interstellar clouds, shedding light on the evolution of the biogenic elements during the process of solar system formation.

Metabolomic approach for determination of key volatile compounds related to beef flavor in glutathione-Maillard reaction products.

PubMed

Lee, Sang Mi; Kwon, Goo Young; Kim, Kwang-Ok; Kim, Young-Suk

2011-10-10

The non-targeted analysis, combining gas chromatography coupled with time-of-flight mass spectrometry (GC-TOF/MS) and sensory evaluation, was applied to investigate the relationship between volatile compounds and the sensory attributes of glutathione-Maillard reaction products (GSH-MRPs) prepared under different reaction conditions. Volatile compounds in GSH-MRPs correlating to the sensory attributes were determined using partial least-squares (PLS) regression. Volatile compounds such as 2-methylfuran-3-thiol, 3-sulfanylpentan-2-one, furan-2-ylmethanethiol, 2-propylpyrazine, 1-furan-2-ylpropan-2-one, 1H-pyrrole, 2-methylthiophene, and 2-(furan-2-ylmethyldisulfanylmethyl)furan could be identified as possible key contributors to the beef-related attributes of GSH-MRPs. In this study, we demonstrated that the unbiased non-targeted analysis based on metabolomic approach allows the identification of key volatile compounds related to beef flavor in GSH-MRPs. Copyright © 2011 Elsevier B.V. All rights reserved.

Identification of internal properties of fibres and micro-swimmers

NASA Astrophysics Data System (ADS)

Plouraboué, Franck; Thiam, E. Ibrahima; Delmotte, Blaise; Climent, Eric

2017-01-01

In this paper, we address the identifiability of constitutive parameters of passive or active micro-swimmers. We first present a general framework for describing fibres or micro-swimmers using a bead-model description. Using a kinematic constraint formulation to describe fibres, flagellum or cilia, we find explicit linear relationship between elastic constitutive parameters and generalized velocities from computing contact forces. This linear formulation then permits one to address explicitly identifiability conditions and solve for parameter identification. We show that both active forcing and passive parameters are both identifiable independently but not simultaneously. We also provide unbiased estimators for generalized elastic parameters in the presence of Langevin-like forcing with Gaussian noise using a Bayesian approach. These theoretical results are illustrated in various configurations showing the efficiency of the proposed approach for direct parameter identification. The convergence of the proposed estimators is successfully tested numerically.

Identification, Collection, and Preservation of Veterinary Forensic Evidence: On Scene and During the Postmortem Examination.

PubMed

Touroo, R; Fitch, A

2016-09-01

Although it is the obligation of the veterinary forensic pathologist to be competent in identifying, collecting, and preserving evidence from the body, it is also necessary for them to understand the relevance of conditions on the crime scene. The body is just one piece of the puzzle that needs to be considered when determining the cause of death. The information required for a complete postmortem analysis should also include details of the animal's environment and items of evidence present on the crime scene. These factors will assist the veterinary forensic pathologist in the interpretation of necropsy findings. Therefore, the veterinary forensic pathologist needs to have a basic understanding of how the crime scene is processed, as well as the role of the forensic veterinarian on scene. In addition, the veterinary forensic pathologist must remain unbiased, necessitating an understanding of evidence maintenance and authentication. © The Author(s) 2016.

Conditioned flavor aversion and location avoidance in hamsters from toxic extract of tall larkspur (Delphinium barbeyi)

USDA-ARS?s Scientific Manuscript database

Studies were conducted to address conditioned flavour aversion (CFA) and place avoidance learning in hamsters given injections of alkaloid extracts from tall larkspur (Delphinium barbeyi), to determine if larkspur had reinforcing or negative properties sufficient to cause place avoidance or preferen...

Deletion of the δ opioid receptor gene impairs place conditioning but preserves morphine reinforcement.

PubMed

Le Merrer, Julie; Plaza-Zabala, Ainhoa; Del Boca, Carolina; Matifas, Audrey; Maldonado, Rafael; Kieffer, Brigitte L

2011-04-01

Converging experimental data indicate that δ opioid receptors contribute to mediate drug reinforcement processes. Whether their contribution reflects a role in the modulation of drug reward or an implication in conditioned learning, however, has not been explored. In the present study, we investigated the impact of δ receptor gene knockout on reinforced conditioned learning under several experimental paradigms. We assessed the ability of δ receptor knockout mice to form drug-context associations with either morphine (appetitive)- or lithium (aversive)-induced Pavlovian place conditioning. We also examined the efficiency of morphine to serve as a positive reinforcer in these mice and their motivation to gain drug injections, with operant intravenous self-administration under fixed and progressive ratio schedules and at two different doses. Mutant mice showed impaired place conditioning in both appetitive and aversive conditions, indicating disrupted context-drug association. In contrast, mutant animals displayed intact acquisition of morphine self-administration and reached breaking-points comparable to control subjects. Thus, reinforcing effects of morphine and motivation to obtain the drug were maintained. Collectively, the data suggest that δ receptor activity is not involved in morphine reinforcement but facilitates place conditioning. This study reveals a novel aspect of δ opioid receptor function in addiction-related behaviors. Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Extinction of conditioned opiate withdrawal in rats in a two-chambered place conditioning apparatus

PubMed Central

Myers, Karyn M.; Bechtholt-Gompf, Anita J.; Coleman, Brian R.; Carlezon, William A.

2016-01-01

Conditioned opiate withdrawal contributes to relapse in addicts and can be studied in rats using the opiate withdrawal-induced conditioned place aversion (OW-CPA) paradigm. Attenuation of conditioned withdrawal through extinction may be beneficial in the treatment of addiction. Here we describe a protocol for studying OW-CPA extinction using a two-chambered place conditioning apparatus. Rats are made dependent on morphine through subcutaneous implantation of morphine pellets and then trained to acquire OW-CPA through pairings of one chamber with naloxone-precipitated withdrawal and the other chamber with saline. Extinction training consists of re-exposures to both chambers in the absence of precipitated withdrawal. Rats tested following the completion of training show a decline in avoidance of the formerly naloxone-paired chamber with increasing numbers of extinction training sessions. The protocol takes a minimum of seven days; the exact duration varies with the amount of extinction training, which is determined by the goals of the experiment. PMID:22362157

Forward conditioning with wheel running causes place aversion in rats.

PubMed

Masaki, Takahisa; Nakajima, Sadahiko

2008-09-01

Backward pairings of a distinctive chamber as a conditioned stimulus and wheel running as an unconditioned stimulus (i.e., running-then-chamber) can produce a conditioned place preference in rats. The present study explored whether a forward conditioning procedure with these stimuli (i.e., chamber-then-running) would yield place preference or aversion. Confinement of a rat in one of two distinctive chambers was followed by a 20- or 60-min running opportunity, but confinement in the other was not. After four repetitions of this treatment (i.e., differential conditioning), a choice preference test was given in which the rat had free access to both chambers. This choice test showed that the rats given 60-min running opportunities spent less time in the running-paired chamber than in the unpaired chamber. Namely, a 60-min running opportunity after confinement in a distinctive chamber caused conditioned aversion to that chamber after four paired trials. This result was discussed with regard to the opponent-process theory of motivation.

Solar Economics for Policymakers | State, Local, and Tribal Governments |

Science.gov Websites

NREL Economics for Policymakers Solar Economics for Policymakers The Solar Technical Assistance regions to give policymakers up-to-date, accurate, and unbiased information on solar economics and likely

Best practices for traffic impact studies : final report.

DOT National Transportation Integrated Search

2006-06-01

For many years there have been concerns that some traffic engineers may approach traffic impact studies with an eye : toward assisting developers expedite their development approval rather than delivering an unbiased evaluation of the : impact of the...

Alternative Fuel Transit Bus Evaluation Program Results

DOT National Transportation Integrated Search

1996-05-06

The objective of this program, which is supported by the U.S. Department of : Energy (DOE) through the National Renewable Energy Laboratory (NREL), is to : provide an unbiased and comprehensive comparison of transit buses operating on : alternative f...

Motor activity as an unbiased variable to assess anaphylaxis in allergic rats

PubMed Central

Abril-Gil, Mar; Garcia-Just, Alba; Cambras, Trinitat; Pérez-Cano, Francisco J; Castellote, Cristina; Franch, Àngels

2015-01-01

The release of mediators by mast cells triggers allergic symptoms involving various physiological systems and, in the most severe cases, the development of anaphylactic shock compromising mainly the nervous and cardiovascular systems. We aimed to establish variables to objectively study the anaphylactic response (AR) after an oral challenge in an allergy model. Brown Norway rats were immunized by intraperitoneal injection of ovalbumin with alum and toxin from Bordetella pertussis. Specific immunoglobulin (Ig) E antibodies were developed in immunized animals. Forty days after immunization, the rats were orally challenged with the allergen, and motor activity, body temperature and serum mast cell protease concentration were determined. The anaphylaxis induced a reduction in body temperature and a decrease in the number of animal movements, which was inversely correlated with serum mast cell protease release. In summary, motor activity is a reliable tool for assessing AR and also an unbiased method for screening new anti-allergic drugs. PMID:25716015

Nonlinear unbiased minimum-variance filter for Mars entry autonomous navigation under large uncertainties and unknown measurement bias.

PubMed

Xiao, Mengli; Zhang, Yongbo; Fu, Huimin; Wang, Zhihua

2018-05-01

High-precision navigation algorithm is essential for the future Mars pinpoint landing mission. The unknown inputs caused by large uncertainties of atmospheric density and aerodynamic coefficients as well as unknown measurement biases may cause large estimation errors of conventional Kalman filters. This paper proposes a derivative-free version of nonlinear unbiased minimum variance filter for Mars entry navigation. This filter has been designed to solve this problem by estimating the state and unknown measurement biases simultaneously with derivative-free character, leading to a high-precision algorithm for the Mars entry navigation. IMU/radio beacons integrated navigation is introduced in the simulation, and the result shows that with or without radio blackout, our proposed filter could achieve an accurate state estimation, much better than the conventional unscented Kalman filter, showing the ability of high-precision Mars entry navigation algorithm. Copyright © 2018 ISA. Published by Elsevier Ltd. All rights reserved.

Unbiased screen for interactors of leucine-rich repeat kinase 2 supports a common pathway for sporadic and familial Parkinson disease

PubMed Central

Beilina, Alexandria; Rudenko, Iakov N.; Kaganovich, Alice; Civiero, Laura; Chau, Hien; Kalia, Suneil K.; Kalia, Lorraine V.; Lobbestael, Evy; Chia, Ruth; Ndukwe, Kelechi; Ding, Jinhui; Nalls, Mike A.; Olszewski, Maciej; Hauser, David N.; Kumaran, Ravindran; Lozano, Andres M.; Baekelandt, Veerle; Greene, Lois E.; Taymans, Jean-Marc; Greggio, Elisa; Cookson, Mark R.; Nalls, Mike A.; Plagnol, Vincent; Martinez, Maria; Hernandez, Dena G; Sharma, Manu; Sheerin, Una-Marie; Saad, Mohamad; Simón-Sánchez, Javier; Schulte, Claudia; Lesage, Suzanne; Sveinbjörnsdóttir, Sigurlaug; Arepalli, Sampath; Barker, Roger; Ben-Shlomo, Yoav; Berendse, Henk W; Berg, Daniela; Bhatia, Kailash; de Bie, Rob M A; Biffi, Alessandro; Bloem, Bas; Bochdanovits, Zoltan; Bonin, Michael; Bras, Jose M; Brockmann, Kathrin; Brooks, Janet; Burn, David J; Charlesworth, Gavin; Chen, Honglei; Chong, Sean; Clarke, Carl E; Cookson, Mark R; Cooper, J Mark; Corvol, Jean Christophe; Counsell, Carl; Damier, Philippe; Dartigues, Jean-François; Deloukas, Panos; Deuschl, Günther; Dexter, David T; van Dijk, Karin D; Dillman, Allissa; Durif, Frank; Dürr, Alexandra; Edkins, Sarah; Evans, Jonathan R; Foltynie, Thomas; Gao, Jianjun; Gardner, Michelle; Gibbs, J Raphael; Goate, Alison; Gray, Emma; Guerreiro, Rita; Gústafsson, Ómar; Harris, Clare; van Hilten, Jacobus J; Hofman, Albert; Hollenbeck, Albert; Holton, Janice; Hu, Michele; Huang, Xuemei; Huber, Heiko; Hudson, Gavin; Hunt, Sarah E; Huttenlocher, Johanna; Illig, Thomas; München, Helmholtz Zentrum; Jónsson, Pálmi V; Lambert, Jean-Charles; Langford, Cordelia; Lees, Andrew; Lichtner, Peter; München, Helmholtz Zentrum; Limousin, Patricia; Lopez, Grisel; Lorenz, Delia; McNeill, Alisdair; Moorby, Catriona; Moore, Matthew; Morris, Huw R; Morrison, Karen E; Mudanohwo, Ese; O’Sullivan, Sean S; Pearson, Justin; Perlmutter, Joel S; Pétursson, Hjörvar; Pollak, Pierre; Post, Bart; Potter, Simon; Ravina, Bernard; Revesz, Tamas; Riess, Olaf; Rivadeneira, Fernando; Rizzu, Patrizia; Ryten, Mina; Sawcer, Stephen; Schapira, Anthony; Scheffer, Hans; Shaw, Karen; Shoulson, Ira; Sidransky, Ellen; Smith, Colin; Spencer, Chris C A; Stefánsson, Hreinn; Steinberg, Stacy; Stockton, Joanna D; Strange, Amy; Talbot, Kevin; Tanner, Carlie M; Tashakkori-Ghanbaria, Avazeh; Tison, François; Trabzuni, Daniah; Traynor, Bryan J; Uitterlinden, André G; Velseboer, Daan; Vidailhet, Marie; Walker, Robert; van de Warrenburg, Bart; Wickremaratchi, Mirdhu; Williams, Nigel; Williams-Gray, Caroline H; Winder-Rhodes, Sophie; Stefánsson, Kári; Hardy, John; Heutink, Peter; Brice, Alexis; Gasser, Thomas; Singleton, Andrew B; Wood, Nicholas W; Chinnery, Patrick F; Arepalli, Sampath; Cookson, Mark R; Dillman, Allissa; Ferrucci, Luigi; Gibbs, J Raphael; Hernandez, Dena G; Johnson, Robert; Longo, Dan L; Majounie, Elisa; Nalls, Michael A; O’Brien, Richard; Singleton, Andrew B; Traynor, Bryan J; Troncoso, Juan; van der Brug, Marcel; Zielke, H Ronald; Zonderman, Alan B

2014-01-01

Mutations in leucine-rich repeat kinase 2 (LRRK2) cause inherited Parkinson disease (PD), and common variants around LRRK2 are a risk factor for sporadic PD. Using protein–protein interaction arrays, we identified BCL2-associated athanogene 5, Rab7L1 (RAB7, member RAS oncogene family-like 1), and Cyclin-G–associated kinase as binding partners of LRRK2. The latter two genes are candidate genes for risk for sporadic PD identified by genome-wide association studies. These proteins form a complex that promotes clearance of Golgi-derived vesicles through the autophagy–lysosome system both in vitro and in vivo. We propose that three different genes for PD have a common biological function. More generally, data integration from multiple unbiased screens can provide insight into human disease mechanisms. PMID:24510904

On the degrees of freedom of reduced-rank estimators in multivariate regression

PubMed Central

Mukherjee, A.; Chen, K.; Wang, N.; Zhu, J.

2015-01-01

Summary We study the effective degrees of freedom of a general class of reduced-rank estimators for multivariate regression in the framework of Stein's unbiased risk estimation. A finite-sample exact unbiased estimator is derived that admits a closed-form expression in terms of the thresholded singular values of the least-squares solution and hence is readily computable. The results continue to hold in the high-dimensional setting where both the predictor and the response dimensions may be larger than the sample size. The derived analytical form facilitates the investigation of theoretical properties and provides new insights into the empirical behaviour of the degrees of freedom. In particular, we examine the differences and connections between the proposed estimator and a commonly-used naive estimator. The use of the proposed estimator leads to efficient and accurate prediction risk estimation and model selection, as demonstrated by simulation studies and a data example. PMID:26702155

GTARG - The TOPEX/Poseidon ground track maintenance maneuver targeting program

NASA Technical Reports Server (NTRS)

Shapiro, Bruce E.; Bhat, Ramachandra S.

1993-01-01

GTARG is a computer program used to design orbit maintenance maneuvers for the TOPEX/Poseidon satellite. These maneuvers ensure that the ground track is kept within +/-1 km with of an = 9.9 day exact repeat pattern. Maneuver parameters are determined using either of two targeting strategies: longitude targeting, which maximizes the time between maneuvers, and time targeting, in which maneuvers are targeted to occur at specific intervals. The GTARG algorithm propagates nonsingular mean elements, taking into account anticipated error sigma's in orbit determination, Delta v execution, drag prediction and Delta v quantization. A satellite unique drag model is used which incorporates an approximate mean orbital Jacchia-Roberts atmosphere and a variable mean area model. Maneuver Delta v magnitudes are targeted to precisely maintain either the unbiased ground track itself, or a comfortable (3 sigma) error envelope about the unbiased ground track.

The New Peabody Picture Vocabulary Test-III: An Illusion of Unbiased Assessment?

PubMed

Stockman, Ida J

2000-10-01

This article examines whether changes in the ethnic minority composition of the standardization sample for the latest edition of the Peabody Picture Vocabulary Test (PPVT-III, Dunn & Dunn, 1997) can be used as the sole explanation for children's better test scores when compared to an earlier edition, the Peabody Picture Vocabulary Test-Revised (PPVT-R, Dunn & Dunn, 1981). Results from a comparative analysis of these two test editions suggest that other factors may explain improved performances. Among these factors are the number of words and age levels sampled, the types of words and pictures used, and characteristics of the standardization sample other than its ethnic minority composition. This analysis also raises questions regarding the usefulness of converting scores from one edition to the other and the type of criteria that could be used to evaluate whether the PPVT-III is an unbiased test of vocabulary for children from diverse cultural and linguistic backgrounds.

Image denoising in mixed Poisson-Gaussian noise.

PubMed

Luisier, Florian; Blu, Thierry; Unser, Michael

2011-03-01

We propose a general methodology (PURE-LET) to design and optimize a wide class of transform-domain thresholding algorithms for denoising images corrupted by mixed Poisson-Gaussian noise. We express the denoising process as a linear expansion of thresholds (LET) that we optimize by relying on a purely data-adaptive unbiased estimate of the mean-squared error (MSE), derived in a non-Bayesian framework (PURE: Poisson-Gaussian unbiased risk estimate). We provide a practical approximation of this theoretical MSE estimate for the tractable optimization of arbitrary transform-domain thresholding. We then propose a pointwise estimator for undecimated filterbank transforms, which consists of subband-adaptive thresholding functions with signal-dependent thresholds that are globally optimized in the image domain. We finally demonstrate the potential of the proposed approach through extensive comparisons with state-of-the-art techniques that are specifically tailored to the estimation of Poisson intensities. We also present denoising results obtained on real images of low-count fluorescence microscopy.

Host Galaxy Morphologies Of Hard X-ray Selected AGN From The Swift BAT Survey

NASA Astrophysics Data System (ADS)

Koss, Michael; Mushotzky, R.; Veilleux, S.

2009-01-01

Surveys of AGN taken in the optical, UV, and soft X-rays miss an important population of obscured AGN only visible in the hard X-rays and mid-IR wavelengths. The SWIFT BAT survey in the hard X-ray range (14-195 keV) has provided a uniquely unbiased sample of 258 AGN unaffected by galactic or circumnuclear absorption. Optical imaging of this unbiased sample provides a new opportunity to understand how the environments of the host galaxies are linked to AGN. For these host galaxies, only a fraction, 29%, have high quality optical images, predominately from the SDSS. In addition, about 33% show peculiar morphologies and interaction. In 2008, we observed 110 of these targets at Kitt Peak with the 2.1m in the SDSS bands over 17 nights. Using these observations and SDSS data we review the relationships between color, morphology, merger activity, star formation, and AGN luminosity.

SIRAH: a structurally unbiased coarse-grained force field for proteins with aqueous solvation and long-range electrostatics.

PubMed

Darré, Leonardo; Machado, Matías Rodrigo; Brandner, Astrid Febe; González, Humberto Carlos; Ferreira, Sebastián; Pantano, Sergio

2015-02-10

Modeling of macromolecular structures and interactions represents an important challenge for computational biology, involving different time and length scales. However, this task can be facilitated through the use of coarse-grained (CG) models, which reduce the number of degrees of freedom and allow efficient exploration of complex conformational spaces. This article presents a new CG protein model named SIRAH, developed to work with explicit solvent and to capture sequence, temperature, and ionic strength effects in a topologically unbiased manner. SIRAH is implemented in GROMACS, and interactions are calculated using a standard pairwise Hamiltonian for classical molecular dynamics simulations. We present a set of simulations that test the capability of SIRAH to produce a qualitatively correct solvation on different amino acids, hydrophilic/hydrophobic interactions, and long-range electrostatic recognition leading to spontaneous association of unstructured peptides and stable structures of single polypeptides and protein-protein complexes.

Biased lineup instructions and face identification from video images.

PubMed

Thompson, W Burt; Johnson, Jaime

2008-01-01

Previous eyewitness memory research has shown that biased lineup instructions reduce identification accuracy, primarily by increasing false-positive identifications in target-absent lineups. Because some attempts at identification do not rely on a witness's memory of the perpetrator but instead involve matching photos to images on surveillance video, the authors investigated the effects of biased instructions on identification accuracy in a matching task. In Experiment 1, biased instructions did not affect the overall accuracy of participants who used video images as an identification aid, but nearly all correct decisions occurred with target-present photo spreads. Both biased and unbiased instructions resulted in high false-positive rates. In Experiment 2, which focused on video-photo matching accuracy with target-absent photo spreads, unbiased instructions led to more correct responses (i.e., fewer false positives). These findings suggest that investigators should not relax precautions against biased instructions when people attempt to match photos to an unfamiliar person recorded on video.

Unbiased approaches to biomarker discovery in neurodegenerative diseases

PubMed Central

Chen-Plotkin, Alice S.

2014-01-01

Neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and frontotemporal dementia have several important features in common. They are progressive, they affect a relatively inaccessible organ, and we have no disease-modifying therapies for them. For these brain-based diseases, current diagnosis and evaluation of disease severity rely almost entirely on clinical examination, which may only be a rough approximation of disease state. Thus, the development of biomarkers – objective, relatively easily measured and precise indicators of pathogenic processes – could improve patient care and accelerate therapeutic discovery. Yet existing, rigorously tested neurodegenerative disease biomarkers are few, and even fewer biomarkers have translated into clinical use. To find new biomarkers for these diseases, an unbiased, high-throughput screening approach may be needed. In this review, I will describe the potential utility of such an approach to biomarker discovery, using Parkinson’s disease as a case example. PMID:25442938

The Swift GRB Host Galaxy Legacy Survey

NASA Astrophysics Data System (ADS)

Perley, Daniel A.

2015-01-01

I introduce the Swift Host Galaxy Legacy Survey (SHOALS), a comprehensive multiwavelength program to characterize the demographics of the GRB host population across its entire redshift range. Using unbiased selection criteria we have designated a subset of 130 Swift gamma-ray bursts which are now being targeted with intensive observational follow-up. Deep Spitzer imaging of every field has already been obtained and analyzed, with major programs ongoing at Keck, GTC, and Gemini to obtain complementary optical/NIR photometry to enable full SED modeling and derivation of fundamental physical parameters such as mass, extinction, and star-formation rate. Using these data I will present an unbiased measurement of the GRB host-galaxy luminosity and mass functions and their evolution with redshift between z=0 and z=5, compare GRB hosts to other star-forming galaxy populations, and discuss implications for the nature of the GRB progenitor and the ability of GRBs to probe cosmic star-formation.

High Efficient THz Emission From Unbiased and Biased Semiconductor Nanowires Fabricated Using Electron Beam Lithography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Balci, Soner; Czaplewski, David A.; Jung, Il Woong

Besides having perfect control on structural features, such as vertical alignment and uniform distribution by fabricating the wires via e-beam lithography and etching process, we also investigated the THz emission from these fabricated nanowires when they are applied DC bias voltage. To be able to apply a voltage bias, an interdigitated gold (Au) electrode was patterned on the high-quality InGaAs epilayer grown on InP substrate bymolecular beam epitaxy. Afterwards, perfect vertically aligned and uniformly distributed nanowires were fabricated in between the electrodes of this interdigitated pattern so that we could apply voltage bias to improve the THz emission. As amore » result, we achieved enhancement in the emitted THz radiation by ~four times, about 12 dB increase in power ratio at 0.25 THz with a DC biased electric field compared with unbiased NWs.« less

Conformational free energy modeling of druglike molecules by metadynamics in the WHIM space.

PubMed

Spiwok, Vojtěch; Hlat-Glembová, Katarína; Tvaroška, Igor; Králová, Blanka

2012-03-26

Protein-ligand affinities can be significantly influenced not only by the interaction itself but also by conformational equilibrium of both binding partners, free ligand and free protein. Identification of important conformational families of a ligand and prediction of their thermodynamics is important for efficient ligand design. Here we report conformational free energy modeling of nine small-molecule drugs in explicitly modeled water by metadynamics with a bias potential applied in the space of weighted holistic invariant molecular (WHIM) descriptors. Application of metadynamics enhances conformational sampling compared to unbiased molecular dynamics simulation and allows to predict relative free energies of key conformations. Selected free energy minima and one example of transition state were tested by a series of unbiased molecular dynamics simulation. Comparison of free energy surfaces of free and target-bound Imatinib provides an estimate of free energy penalty of conformational change induced by its binding to the target. © 2012 American Chemical Society

Unbiased free energy estimates in fast nonequilibrium transformations using Gaussian mixtures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Procacci, Piero

2015-04-21

In this paper, we present an improved method for obtaining unbiased estimates of the free energy difference between two thermodynamic states using the work distribution measured in nonequilibrium driven experiments connecting these states. The method is based on the assumption that any observed work distribution is given by a mixture of Gaussian distributions, whose normal components are identical in either direction of the nonequilibrium process, with weights regulated by the Crooks theorem. Using the prototypical example for the driven unfolding/folding of deca-alanine, we show that the predicted behavior of the forward and reverse work distributions, assuming a combination of onlymore » two Gaussian components with Crooks derived weights, explains surprisingly well the striking asymmetry in the observed distributions at fast pulling speeds. The proposed methodology opens the way for a perfectly parallel implementation of Jarzynski-based free energy calculations in complex systems.« less

Functional annotation of chemical libraries across diverse biological processes.

PubMed

Piotrowski, Jeff S; Li, Sheena C; Deshpande, Raamesh; Simpkins, Scott W; Nelson, Justin; Yashiroda, Yoko; Barber, Jacqueline M; Safizadeh, Hamid; Wilson, Erin; Okada, Hiroki; Gebre, Abraham A; Kubo, Karen; Torres, Nikko P; LeBlanc, Marissa A; Andrusiak, Kerry; Okamoto, Reika; Yoshimura, Mami; DeRango-Adem, Eva; van Leeuwen, Jolanda; Shirahige, Katsuhiko; Baryshnikova, Anastasia; Brown, Grant W; Hirano, Hiroyuki; Costanzo, Michael; Andrews, Brenda; Ohya, Yoshikazu; Osada, Hiroyuki; Yoshida, Minoru; Myers, Chad L; Boone, Charles

2017-09-01

Chemical-genetic approaches offer the potential for unbiased functional annotation of chemical libraries. Mutations can alter the response of cells in the presence of a compound, revealing chemical-genetic interactions that can elucidate a compound's mode of action. We developed a highly parallel, unbiased yeast chemical-genetic screening system involving three key components. First, in a drug-sensitive genetic background, we constructed an optimized diagnostic mutant collection that is predictive for all major yeast biological processes. Second, we implemented a multiplexed (768-plex) barcode-sequencing protocol, enabling the assembly of thousands of chemical-genetic profiles. Finally, based on comparison of the chemical-genetic profiles with a compendium of genome-wide genetic interaction profiles, we predicted compound functionality. Applying this high-throughput approach, we screened seven different compound libraries and annotated their functional diversity. We further validated biological process predictions, prioritized a diverse set of compounds, and identified compounds that appear to have dual modes of action.

Best Linear Unbiased Prediction (BLUP) for regional yield trials: a comparison to additive main effects and multiplicative interaction (AMMI) analysis.

PubMed

Piepho, H P

1994-11-01

Multilocation trials are often used to analyse the adaptability of genotypes in different environments and to find for each environment the genotype that is best adapted; i.e. that is highest yielding in that environment. For this purpose, it is of interest to obtain a reliable estimate of the mean yield of a cultivar in a given environment. This article compares two different statistical estimation procedures for this task: the Additive Main Effects and Multiplicative Interaction (AMMI) analysis and Best Linear Unbiased Prediction (BLUP). A modification of a cross validation procedure commonly used with AMMI is suggested for trials that are laid out as a randomized complete block design. The use of these procedure is exemplified using five faba bean datasets from German registration trails. BLUP was found to outperform AMMI in four of five faba bean datasets.

Modeling long period swell in Southern California: Practical boundary conditions from buoy observations and global wave model predictions

NASA Astrophysics Data System (ADS)

Crosby, S. C.; O'Reilly, W. C.; Guza, R. T.

2016-02-01

Accurate, unbiased, high-resolution (in space and time) nearshore wave predictions are needed to drive models of beach erosion, coastal flooding, and alongshore transport of sediment, biota and pollutants. On highly sheltered shorelines, wave predictions are sensitive to the directions of onshore propagating waves, and nearshore model prediction error is often dominated by uncertainty in offshore boundary conditions. Offshore islands and shoals, and coastline curvature, create complex sheltering patterns over the 250km span of southern California (SC) shoreline. Here, regional wave model skill in SC was compared for different offshore boundary conditions created using offshore buoy observations and global wave model hindcasts (National Oceanographic and Atmospheric Administration Wave Watch 3, WW3). Spectral ray-tracing methods were used to transform incident offshore swell (0.04-0.09Hz) energy at high directional resolution (1-deg). Model skill is assessed for predictions (wave height, direction, and alongshore radiation stress) at 16 nearshore buoy sites between 2000 and 2009. Model skill using buoy-derived boundary conditions is higher than with WW3-derived boundary conditions. Buoy-driven nearshore model results are similar with various assumptions about the true offshore directional distribution (maximum entropy, Bayesian direct, and 2nd derivative smoothness). Two methods combining offshore buoy observations with WW3 predictions in the offshore boundary condition did not improve nearshore skill above buoy-only methods. A case example at Oceanside harbor shows strong sensitivity of alongshore sediment transport predictions to different offshore boundary conditions. Despite this uncertainty in alongshore transport magnitude, alongshore gradients in transport (e.g. the location of model accretion and erosion zones) are determined by the local bathymetry, and are similar for all predictions.

Short Course Introduction to Quantitative Mineral Resource Assessments

USGS Publications Warehouse

Singer, Donald A.

2007-01-01

This is an abbreviated text supplementing the content of three sets of slides used in a short course that has been presented by the author at several workshops. The slides should be viewed in the order of (1) Introduction and models, (2) Delineation and estimation, and (3) Combining estimates and summary. References cited in the slides are listed at the end of this text. The purpose of the three-part form of mineral resource assessments discussed in the accompanying slides is to make unbiased quantitative assessments in a format needed in decision-support systems so that consequences of alternative courses of action can be examined. The three-part form of mineral resource assessments was developed to assist policy makers evaluate the consequences of alternative courses of action with respect to land use and mineral-resource development. The audience for three-part assessments is a governmental or industrial policy maker, a manager of exploration, a planner of regional development, or similar decision-maker. Some of the tools and models presented here will be useful for selection of exploration sites, but that is a side benefit, not the goal. To provide unbiased information, we recommend the three-part form of mineral resource assessments where general locations of undiscovered deposits are delineated from a deposit type's geologic setting, frequency distributions of tonnages and grades of well-explored deposits serve as models of grades and tonnages of undiscovered deposits, and number of undiscovered deposits are estimated probabilistically by type. The internally consistent descriptive, grade and tonnage, deposit density, and economic models used in the design of the three-part form of assessments reduce the chances of biased estimates of the undiscovered resources. What and why quantitative resource assessments: The kind of assessment recommended here is founded in decision analysis in order to provide a framework for making decisions concerning mineral resources under conditions of uncertainty. What this means is that we start with the question of what kinds of questions is the decision maker trying to resolve and what forms of information would aid in resolving these questions. Some applications of mineral resource assessments: To plan and guide exploration programs, to assist in land use planning, to plan the location of infrastructure, to estimate mineral endowment, and to identify deposits that present special environmental challenges. Why not just rank prospects / areas? Need for financial analysis, need for comparison with other land uses, need for comparison with distant tracts of land, need to know how uncertain the estimates are, need for consideration of economic and environmental consequences of possible development. Our goal is to provide unbiased information useful to decision-makers.

Quantifying the accretion of hyperphosphorylated tau in the locus coeruleus and dorsal raphe nucleus: the pathological building blocks of early Alzheimer's disease.

PubMed

Ehrenberg, A J; Nguy, A K; Theofilas, P; Dunlop, S; Suemoto, C K; Di Lorenzo Alho, A T; Leite, R P; Diehl Rodriguez, R; Mejia, M B; Rüb, U; Farfel, J M; de Lucena Ferretti-Rebustini, R E; Nascimento, C F; Nitrini, R; Pasquallucci, C A; Jacob-Filho, W; Miller, B; Seeley, W W; Heinsen, H; Grinberg, L T

2017-08-01

Hyperphosphorylated tau neuronal cytoplasmic inclusions (ht-NCI) are the best protein correlate of clinical decline in Alzheimer's disease (AD). Qualitative evidence identifies ht-NCI accumulating in the isodendritic core before the entorhinal cortex. Here, we used unbiased stereology to quantify ht-NCI burden in the locus coeruleus (LC) and dorsal raphe nucleus (DRN), aiming to characterize the impact of AD pathology in these nuclei with a focus on early stages. We utilized unbiased stereology in a sample of 48 well-characterized subjects enriched for controls and early AD stages. ht-NCI counts were estimated in 60-μm-thick sections immunostained for p-tau throughout LC and DRN. Data were integrated with unbiased estimates of LC and DRN neuronal population for a subset of cases. In Braak stage 0, 7.9% and 2.6% of neurons in LC and DRN, respectively, harbour ht-NCIs. Although the number of ht-NCI+ neurons significantly increased by about 1.9× between Braak stages 0 to I in LC (P = 0.02), we failed to detect any significant difference between Braak stage I and II. Also, the number of ht-NCI+ neurons remained stable in DRN between all stages 0 and II. Finally, the differential susceptibility to tau inclusions among nuclear subdivisions was more notable in LC than in DRN. LC and DRN neurons exhibited ht-NCI during AD precortical stages. The ht-NCI increases along AD progression on both nuclei, but quantitative changes in LC precede DRN changes. © 2017 British Neuropathological Society.

A Stereological Method for the Quantitative Evaluation of Cartilage Repair Tissue

PubMed Central

Nyengaard, Jens Randel; Lind, Martin; Spector, Myron

2015-01-01

Objective To implement stereological principles to develop an easy applicable algorithm for unbiased and quantitative evaluation of cartilage repair. Design Design-unbiased sampling was performed by systematically sectioning the defect perpendicular to the joint surface in parallel planes providing 7 to 10 hematoxylin–eosin stained histological sections. Counting windows were systematically selected and converted into image files (40-50 per defect). The quantification was performed by two-step point counting: (1) calculation of defect volume and (2) quantitative analysis of tissue composition. Step 2 was performed by assigning each point to one of the following categories based on validated and easy distinguishable morphological characteristics: (1) hyaline cartilage (rounded cells in lacunae in hyaline matrix), (2) fibrocartilage (rounded cells in lacunae in fibrous matrix), (3) fibrous tissue (elongated cells in fibrous tissue), (4) bone, (5) scaffold material, and (6) others. The ability to discriminate between the tissue types was determined using conventional or polarized light microscopy, and the interobserver variability was evaluated. Results We describe the application of the stereological method. In the example, we assessed the defect repair tissue volume to be 4.4 mm3 (CE = 0.01). The tissue fractions were subsequently evaluated. Polarized light illumination of the slides improved discrimination between hyaline cartilage and fibrocartilage and increased the interobserver agreement compared with conventional transmitted light. Conclusion We have applied a design-unbiased method for quantitative evaluation of cartilage repair, and we propose this algorithm as a natural supplement to existing descriptive semiquantitative scoring systems. We also propose that polarized light is effective for discrimination between hyaline cartilage and fibrocartilage. PMID:26069715

Reconsidering Cluster Bias in Multilevel Data: A Monte Carlo Comparison of Free and Constrained Baseline Approaches.

PubMed

Guenole, Nigel

2018-01-01

The test for item level cluster bias examines the improvement in model fit that results from freeing an item's between level residual variance from a baseline model with equal within and between level factor loadings and between level residual variances fixed at zero. A potential problem is that this approach may include a misspecified unrestricted model if any non-invariance is present, but the log-likelihood difference test requires that the unrestricted model is correctly specified. A free baseline approach where the unrestricted model includes only the restrictions needed for model identification should lead to better decision accuracy, but no studies have examined this yet. We ran a Monte Carlo study to investigate this issue. When the referent item is unbiased, compared to the free baseline approach, the constrained baseline approach led to similar true positive (power) rates but much higher false positive (Type I error) rates. The free baseline approach should be preferred when the referent indicator is unbiased. When the referent assumption is violated, the false positive rate was unacceptably high for both free and constrained baseline approaches, and the true positive rate was poor regardless of whether the free or constrained baseline approach was used. Neither the free or constrained baseline approach can be recommended when the referent indicator is biased. We recommend paying close attention to ensuring the referent indicator is unbiased in tests of cluster bias. All Mplus input and output files, R, and short Python scripts used to execute this simulation study are uploaded to an open access repository.

Unbiased in-depth characterization of CEX fractions from a stressed monoclonal antibody by mass spectrometry.

PubMed

Griaud, François; Denefeld, Blandine; Lang, Manuel; Hensinger, Héloïse; Haberl, Peter; Berg, Matthias

2017-07-01

Characterization of charge-based variants by mass spectrometry (MS) is required for the analytical development of a new biologic entity and its marketing approval by health authorities. However, standard peak-based data analysis approaches are time-consuming and biased toward the detection, identification, and quantification of main variants only. The aim of this study was to characterize in-depth acidic and basic species of a stressed IgG1 monoclonal antibody using comprehensive and unbiased MS data evaluation tools. Fractions collected from cation ion exchange (CEX) chromatography were analyzed as intact, after reduction of disulfide bridges, and after proteolytic cleavage using Lys-C. Data of both intact and reduced samples were evaluated consistently using a time-resolved deconvolution algorithm. Peptide mapping data were processed simultaneously, quantified and compared in a systematic manner for all MS signals and fractions. Differences observed between the fractions were then further characterized and assigned. Time-resolved deconvolution enhanced pattern visualization and data interpretation of main and minor modifications in 3-dimensional maps across CEX fractions. Relative quantification of all MS signals across CEX fractions before peptide assignment enabled the detection of fraction-specific chemical modifications at abundances below 1%. Acidic fractions were shown to be heterogeneous, containing antibody fragments, glycated as well as deamidated forms of the heavy and light chains. In contrast, the basic fractions contained mainly modifications of the C-terminus and pyroglutamate formation at the N-terminus of the heavy chain. Systematic data evaluation was performed to investigate multiple data sets and comprehensively extract main and minor differences between each CEX fraction in an unbiased manner.

Unbiased metabolite profiling by liquid chromatography-quadrupole time-of-flight mass spectrometry and multivariate data analysis for herbal authentication: classification of seven Lonicera species flower buds.

PubMed

Gao, Wen; Yang, Hua; Qi, Lian-Wen; Liu, E-Hu; Ren, Mei-Ting; Yan, Yu-Ting; Chen, Jun; Li, Ping

2012-07-06

Plant-based medicines become increasingly popular over the world. Authentication of herbal raw materials is important to ensure their safety and efficacy. Some herbs belonging to closely related species but differing in medicinal properties are difficult to be identified because of similar morphological and microscopic characteristics. Chromatographic fingerprinting is an alternative method to distinguish them. Existing approaches do not allow a comprehensive analysis for herbal authentication. We have now developed a strategy consisting of (1) full metabolic profiling of herbal medicines by rapid resolution liquid chromatography (RRLC) combined with quadrupole time-of-flight mass spectrometry (QTOF MS), (2) global analysis of non-targeted compounds by molecular feature extraction algorithm, (3) multivariate statistical analysis for classification and prediction, and (4) marker compounds characterization. This approach has provided a fast and unbiased comparative multivariate analysis of the metabolite composition of 33-batch samples covering seven Lonicera species. Individual metabolic profiles are performed at the level of molecular fragments without prior structural assignment. In the entire set, the obtained classifier for seven Lonicera species flower buds showed good prediction performance and a total of 82 statistically different components were rapidly obtained by the strategy. The elemental compositions of discriminative metabolites were characterized by the accurate mass measurement of the pseudomolecular ions and their chemical types were assigned by the MS/MS spectra. The high-resolution, comprehensive and unbiased strategy for metabolite data analysis presented here is powerful and opens the new direction of authentication in herbal analysis. Copyright © 2012 Elsevier B.V. All rights reserved.

Estimating unbiased economies of scale of HIV prevention projects: a case study of Avahan.

PubMed

Lépine, Aurélia; Vassall, Anna; Chandrashekar, Sudha; Blanc, Elodie; Le Nestour, Alexis

2015-04-01

Governments and donors are investing considerable resources on HIV prevention in order to scale up these services rapidly. Given the current economic climate, providers of HIV prevention services increasingly need to demonstrate that these investments offer good 'value for money'. One of the primary routes to achieve efficiency is to take advantage of economies of scale (a reduction in the average cost of a health service as provision scales-up), yet empirical evidence on economies of scale is scarce. Methodologically, the estimation of economies of scale is hampered by several statistical issues preventing causal inference and thus making the estimation of economies of scale complex. In order to estimate unbiased economies of scale when scaling up HIV prevention services, we apply our analysis to one of the few HIV prevention programmes globally delivered at a large scale: the Indian Avahan initiative. We costed the project by collecting data from the 138 Avahan NGOs and the supporting partners in the first four years of its scale-up, between 2004 and 2007. We develop a parsimonious empirical model and apply a system Generalized Method of Moments (GMM) and fixed-effects Instrumental Variable (IV) estimators to estimate unbiased economies of scale. At the programme level, we find that, after controlling for the endogeneity of scale, the scale-up of Avahan has generated high economies of scale. Our findings suggest that average cost reductions per person reached are achievable when scaling-up HIV prevention in low and middle income countries. Copyright © 2015 Elsevier Ltd. All rights reserved.

Reconsidering Cluster Bias in Multilevel Data: A Monte Carlo Comparison of Free and Constrained Baseline Approaches

PubMed Central

Guenole, Nigel

2018-01-01

The test for item level cluster bias examines the improvement in model fit that results from freeing an item's between level residual variance from a baseline model with equal within and between level factor loadings and between level residual variances fixed at zero. A potential problem is that this approach may include a misspecified unrestricted model if any non-invariance is present, but the log-likelihood difference test requires that the unrestricted model is correctly specified. A free baseline approach where the unrestricted model includes only the restrictions needed for model identification should lead to better decision accuracy, but no studies have examined this yet. We ran a Monte Carlo study to investigate this issue. When the referent item is unbiased, compared to the free baseline approach, the constrained baseline approach led to similar true positive (power) rates but much higher false positive (Type I error) rates. The free baseline approach should be preferred when the referent indicator is unbiased. When the referent assumption is violated, the false positive rate was unacceptably high for both free and constrained baseline approaches, and the true positive rate was poor regardless of whether the free or constrained baseline approach was used. Neither the free or constrained baseline approach can be recommended when the referent indicator is biased. We recommend paying close attention to ensuring the referent indicator is unbiased in tests of cluster bias. All Mplus input and output files, R, and short Python scripts used to execute this simulation study are uploaded to an open access repository. PMID:29551985

Regression calibration for models with two predictor variables measured with error and their interaction, using instrumental variables and longitudinal data.

PubMed

Strand, Matthew; Sillau, Stefan; Grunwald, Gary K; Rabinovitch, Nathan

2014-02-10

Regression calibration provides a way to obtain unbiased estimators of fixed effects in regression models when one or more predictors are measured with error. Recent development of measurement error methods has focused on models that include interaction terms between measured-with-error predictors, and separately, methods for estimation in models that account for correlated data. In this work, we derive explicit and novel forms of regression calibration estimators and associated asymptotic variances for longitudinal models that include interaction terms, when data from instrumental and unbiased surrogate variables are available but not the actual predictors of interest. The longitudinal data are fit using linear mixed models that contain random intercepts and account for serial correlation and unequally spaced observations. The motivating application involves a longitudinal study of exposure to two pollutants (predictors) - outdoor fine particulate matter and cigarette smoke - and their association in interactive form with levels of a biomarker of inflammation, leukotriene E4 (LTE 4 , outcome) in asthmatic children. Because the exposure concentrations could not be directly observed, we used measurements from a fixed outdoor monitor and urinary cotinine concentrations as instrumental variables, and we used concentrations of fine ambient particulate matter and cigarette smoke measured with error by personal monitors as unbiased surrogate variables. We applied the derived regression calibration methods to estimate coefficients of the unobserved predictors and their interaction, allowing for direct comparison of toxicity of the different pollutants. We used simulations to verify accuracy of inferential methods based on asymptotic theory. Copyright © 2013 John Wiley & Sons, Ltd.

A Stereological Method for the Quantitative Evaluation of Cartilage Repair Tissue.

PubMed

Foldager, Casper Bindzus; Nyengaard, Jens Randel; Lind, Martin; Spector, Myron

2015-04-01

To implement stereological principles to develop an easy applicable algorithm for unbiased and quantitative evaluation of cartilage repair. Design-unbiased sampling was performed by systematically sectioning the defect perpendicular to the joint surface in parallel planes providing 7 to 10 hematoxylin-eosin stained histological sections. Counting windows were systematically selected and converted into image files (40-50 per defect). The quantification was performed by two-step point counting: (1) calculation of defect volume and (2) quantitative analysis of tissue composition. Step 2 was performed by assigning each point to one of the following categories based on validated and easy distinguishable morphological characteristics: (1) hyaline cartilage (rounded cells in lacunae in hyaline matrix), (2) fibrocartilage (rounded cells in lacunae in fibrous matrix), (3) fibrous tissue (elongated cells in fibrous tissue), (4) bone, (5) scaffold material, and (6) others. The ability to discriminate between the tissue types was determined using conventional or polarized light microscopy, and the interobserver variability was evaluated. We describe the application of the stereological method. In the example, we assessed the defect repair tissue volume to be 4.4 mm(3) (CE = 0.01). The tissue fractions were subsequently evaluated. Polarized light illumination of the slides improved discrimination between hyaline cartilage and fibrocartilage and increased the interobserver agreement compared with conventional transmitted light. We have applied a design-unbiased method for quantitative evaluation of cartilage repair, and we propose this algorithm as a natural supplement to existing descriptive semiquantitative scoring systems. We also propose that polarized light is effective for discrimination between hyaline cartilage and fibrocartilage.

The effects of inhaled acetone on place conditioning in adolescent rats

PubMed Central

Lee, Dianne E.; Pai, Jennifer; Mullapudui, Uma; Alexoff, David L.; Ferrieri, Richard; Dewey, Stephen L.

2009-01-01

Introduction Acetone is a ubiquitous ingredient in many household products (e.g., glue solvents, air fresheners, adhesives, nail polish, and paint) that is putatively abused; however, there is little empirical evidence to suggest that acetone alone has any abuse liability. Therefore, we systematically investigated the conditioned response to inhaled acetone in a place conditioning apparatus. Method Three groups of male, Sprague-Dawley rats were exposed to acetone concentrations of 5,000, 10,000 or 20,000 ppm for 1 hour in a conditioned place preference apparatus alternating with air for 6 pairing sessions. A place preference test ensued in an acetone-free environment. To test the preference of acetone as a function of pairings sessions, the 10,000 ppm group received an additional 6 pairings and an additional group received 3 pairings. The control group received air in both compartments. Locomotor activity was recorded by infrared photocells during each pairing session. Results We noted a dose response relationship to acetone at levels 5,000-20,000 ppm. However, there was no correlation of place preference as a function of pairing sessions at the 10,000 ppm level. Locomotor activity was markedly decreased in animals on acetone-paired days as compared to air-paired days. Conclusion The acetone concentrations we tested for these experiments produced a markedly decreased locomotor activity profile that resemble CNS depressants. Furthermore, a dose response relationship was observed at these pharmacologically active concentrations, however, animals did not exhibit a positive place preference. PMID:18096214

Conditioned place preferences in humans using virtual reality.

PubMed

Astur, Robert S; Carew, Andrew W; Deaton, Bonnie E

2014-07-01

To extend a standard paradigm of conditioning in nonhumans to humans, we created a virtual reality (VR) conditioned place preference task, with real-life food rewards. Undergraduates were placed into a VR environment consisting of 2 visually distinct rooms. On Day 1, participants underwent 6 pairing sessions in which they were confined into one of the two rooms and explored the VR environment. Room A was paired with real-life M&Ms for 3 sessions, and Room B was paired with no food for 3 sessions. Day 2 was the test day, administered the next day, and participants were given free access to the entire VR environment for 5min. In experiment 1, participants were food restricted, and we observed that on the test day, participants display a significant conditioned place preference for the VR room previously paired with food (p<0.001). Additionally, they display a significant explicit preference for the M&M-paired room in a forced-choice of "Which room do you like best?". In experiment 2, when participants were not food restricted, there was no evidence of a place preference, either implicitly (e.g. dwell time) or explicitly. Hence, we show that we can reliably establish a place preference in humans, but that the preference is contingent on the participants' hunger state. Future research will examine the extent to which these preferences can be blocked or extinguished as well as whether these preferences are evident using other reinforcers. Copyright © 2014 Elsevier B.V. All rights reserved.

7 CFR 1980.454 - Conditions precedent to issuance of the Loan Note Guarantee.

Code of Federal Regulations, 2010 CFR

2010-01-01

... new eligible lender in place of a former lender who holds an outstanding Conditional Commitment for... to the scope of the project, overall facility concept, project purpose, use of proceeds or terms and... financial statements of the borrower to assure that no adverse change has taken place. The District Director...

30 CFR 1206.362 - What are my responsibilities to place production into marketable condition and to market production?

Code of Federal Regulations, 2013 CFR

2013-07-01

... 30 Mineral Resources 3 2013-07-01 2013-07-01 false What are my responsibilities to place production into marketable condition and to market production? 1206.362 Section 1206.362 Mineral Resources OFFICE OF NATURAL RESOURCES REVENUE, DEPARTMENT OF THE INTERIOR NATURAL RESOURCES REVENUE PRODUCT...

30 CFR 1206.106 - What are my responsibilities to place production into marketable condition and to market production?

Code of Federal Regulations, 2012 CFR

2012-07-01

... 30 Mineral Resources 3 2012-07-01 2012-07-01 false What are my responsibilities to place production into marketable condition and to market production? 1206.106 Section 1206.106 Mineral Resources OFFICE OF NATURAL RESOURCES REVENUE, DEPARTMENT OF THE INTERIOR NATURAL RESOURCES REVENUE PRODUCT...

30 CFR 1206.362 - What are my responsibilities to place production into marketable condition and to market production?

Code of Federal Regulations, 2012 CFR

2012-07-01

... 30 Mineral Resources 3 2012-07-01 2012-07-01 false What are my responsibilities to place production into marketable condition and to market production? 1206.362 Section 1206.362 Mineral Resources OFFICE OF NATURAL RESOURCES REVENUE, DEPARTMENT OF THE INTERIOR NATURAL RESOURCES REVENUE PRODUCT...

30 CFR 1206.106 - What are my responsibilities to place production into marketable condition and to market production?

Code of Federal Regulations, 2014 CFR

2014-07-01

... 30 Mineral Resources 3 2014-07-01 2014-07-01 false What are my responsibilities to place production into marketable condition and to market production? 1206.106 Section 1206.106 Mineral Resources OFFICE OF NATURAL RESOURCES REVENUE, DEPARTMENT OF THE INTERIOR NATURAL RESOURCES REVENUE PRODUCT...

30 CFR 1206.362 - What are my responsibilities to place production into marketable condition and to market production?

Code of Federal Regulations, 2014 CFR

2014-07-01

... 30 Mineral Resources 3 2014-07-01 2014-07-01 false What are my responsibilities to place production into marketable condition and to market production? 1206.362 Section 1206.362 Mineral Resources OFFICE OF NATURAL RESOURCES REVENUE, DEPARTMENT OF THE INTERIOR NATURAL RESOURCES REVENUE PRODUCT...

30 CFR 1206.106 - What are my responsibilities to place production into marketable condition and to market production?

Code of Federal Regulations, 2013 CFR

2013-07-01

... 30 Mineral Resources 3 2013-07-01 2013-07-01 false What are my responsibilities to place production into marketable condition and to market production? 1206.106 Section 1206.106 Mineral Resources OFFICE OF NATURAL RESOURCES REVENUE, DEPARTMENT OF THE INTERIOR NATURAL RESOURCES REVENUE PRODUCT...

Anxiety status affects nicotine- and baclofen-induced locomotor activity, anxiety, and single-trial conditioned place preference in male adolescent rats.

PubMed

Falco, Adriana M; McDonald, Craig G; Smith, Robert F

2014-09-01

Adolescents have an increased vulnerability to nicotine and anxiety may play a role in the development of nicotine abuse. One possible treatment for anxiety disorders and substance abuse is the GABAB agonist, baclofen. The aim of the present study was to determine the effect of anxiety-like behavior on single-trial nicotine conditioned place preference in adolescent rats, and to assess the action of baclofen. Baclofen was shown to have effects on locomotor and anxiety-like behavior in rats divided into high-anxiety and low-anxiety groups. Baclofen decreased locomotor behavior in high-anxiety rats. Baclofen alone failed to produce differences in anxiety-like behavior, but nicotine and baclofen + nicotine administration were anxiolytic. High- and low-anxiety groups also showed differences in single-trial nicotine-induced place preference. Only high-anxiety rats formed place preference to nicotine, while rats in the low-anxiety group formed no conditioned place preference. These results suggest that among adolescents, high-anxiety individuals are more likely to show preference for nicotine than low-anxiety individuals. © 2014 Wiley Periodicals, Inc.

Can we accelerate medicinal chemistry by augmenting the chemist with Big Data and artificial intelligence?

PubMed

Griffen, Edward J; Dossetter, Alexander G; Leach, Andrew G; Montague, Shane

2018-03-22

AI comes to lead optimization: medicinal chemistry in all disease areas can be accelerated by exploiting our pre-competitive knowledge in an unbiased way. Copyright © 2018 Elsevier Ltd. All rights reserved.

Fuel Cell Transit Bus Coordination and Evaluation Plan California Fuel Cell Transit Evaluation Team, DRAFT

DOT National Transportation Integrated Search

2003-10-29

The objective of the DOE/NREL evaluation program is to provide comprehensive, unbiased evaluation results of advanced technology vehicle development and operations, evaluation of hydrogen infrastructure development and operation, and descriptions of ...

Battery testing at Argonne National Laboratory

NASA Astrophysics Data System (ADS)

Deluca, W. H.; Gillie, K. R.; Kulaga, J. E.; Smaga, J. A.; Tummillo, A. F.; Webster, C. E.

Advanced battery technology evaluations are performed under simulated electric-vehicle operating conditions at the Analysis & Diagnostic Laboratory (ADL) of Argonne National Laboratory. The ADL results provide insight into those factors that limit battery performance and life. The ADL facilities include a test laboratory to conduct battery experimental evaluations under simulated application conditions and a post-test analysis laboratory to determine, in a protected atmosphere if needed, component compositional changes and failure mechanisms. This paper summarizes the performance characterizations and life evaluations conducted during FY-92 on both single cells and multi-cell modules that encompass six battery technologies (Na/S, Li/FeS, Ni/Metal-Hydride, Ni/Zn, Ni/Cd, Ni/Fe). These evaluations were performed for the Department of Energy, Office of Transportation Technologies, Electric and Hybrid Propulsion Division, and the Electric Power Research Institute. The ADL provides a common basis for battery performance characterization and life evaluations with unbiased application of tests and analyses. The results help identify the most promising R&D approaches for overcoming battery limitations, and provide battery users, developers, and program managers with a measure of the progress being made in battery R&D programs, a comparison of battery technologies, and basic data for modeling.

Provision of fertility services for women at increased risk of complications during fertility treatment or pregnancy: an Ethics Committee opinion.

PubMed

2016-11-01

This opinion addresses the ethics of providing fertility treatment to women at elevated risk from fertility treatment or pregnancy. Providers ethically may treat women at elevated risk provided that they are carefully assessed; that specialists in their medical condition are consulted as appropriate; and that patients are fully informed about risks, benefits, and alternatives, including oocyte and embryo donation, use of a gestational surrogate, not undergoing fertility care, and adoption. Providers also may conclude that the risks are too high for them to treat particular patients ethically; such determinations must be made in a medically objective and unbiased manner and patients must be fully informed of the decision. Counseling of women who wish to initiate fertility treatment with underlying medical conditions that confer increased risk during treatment or pregnancy should incorporate the most current knowledge available, being cognizant of the woman's personal determinants in relation to her reproductive desires. In such a way, both physician and patient will optimize decision making in an ethically sound, patient-supportive context. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Reinstatement of cocaine place-conditioning prevented by the peptide kappa-opioid receptor antagonist arodyn.

PubMed

Carey, A N; Borozny, K; Aldrich, J V; McLaughlin, J P

2007-08-13

Stress contributes to the reinstatement of cocaine-seeking behavior in abstinent subjects. Kappa-opioid receptor antagonists attenuate the behavioral effects of stress, potentially providing therapeutic value in treating cocaine abuse. Presently, the peptide arodyn produced long-lasting kappa-opioid receptor antagonism, suppressing kappa-opioid receptor agonist-induced antinociception at least 3 days after intracerebroventricular administration of 0.3 nmol. C57Bl/6J mice demonstrated cocaine-conditioned place preference, extinction over 3 weeks, and a subsequent reinstatement of place preference. Arodyn pretreatment suppressed stress-induced, but not cocaine-exposed, reinstatement of cocaine place preference. These results verify that arodyn and other kappa-opioid receptor antagonists may be useful therapeutics for cocaine abuse.

Cerebellar Structure and Function in Male Wistar-Kyoto Hyperactive Rats

PubMed Central

Thanellou, Alexandra; Green, John T.

2014-01-01

Previous research has suggested that the Wistar-Kyoto Hyperactive (WKHA) rat strain may model some of the behavioral features associated with attention-deficit/hyperactivity disorder (ADHD). We have shown that, in cerebellar-dependent eyeblink conditioning, WKHA emit eyeblink CRs with shortened onset latencies. To further characterize the shortened CR onset latencies seen in WKHA rats, we examined 750-ms delay conditioning with either a tone CS or a light CS, we extended acquisition training, and we included Wistar rats as an additional, outbred control strain. Our results indicated that WKHAs learned more quickly and showed a shortened CR onset latency to a tone CS compared to both Wistar-Kyoto Hypertensive (WKHT) and Wistars. WKHAs and Wistars show a lengthening of CR onset latency over conditioning with a tone CS and an increasing confinement of CRs to the later part of the tone CS (inhibition of delay). WKHAs learned more quickly to a light CS only in comparison to WKHTs and showed a shortened CR onset latency only in comparison to Wistars. Wistars showed an increasing confinement of CRs to the late part of the light CS over conditioning. We used unbiased stereology to estimate the number of Purkinje and granule cells in the cerebellar cortex of the three strains. Our results indicated that WKHAs have more granule cells than Wistars and WKHTs and more Purkinje cells than Wistars. Results are discussed in terms of CS processing and cerebellar cortical contributions to EBC. PMID:23398437

Impact of suggestion on the human experimental model of cold hyperalgesia after topical application of high-concentration menthol [40%].

PubMed

Helfert, S; Reimer, M; Barnscheid, L; Hüllemann, P; Rengelshausen, J; Keller, T; Baron, R; Binder, A

2018-05-14

Human experimental pain models in healthy subjects offer unique possibilities to study mechanisms of pain within a defined setting of expected pain symptoms, signs and mechanisms. Previous trials in healthy subjects demonstrated that topical application of 40% menthol is suitable to induce cold hyperalgesia. The objective of this study was to evaluate the impact of suggestion on this experimental human pain model. The study was performed within a single-centre, randomized, placebo-controlled, double-blind, two-period crossover trial in a cohort of 16 healthy subjects. Subjects were tested twice after topical menthol application (40% dissolved in ethanol) and twice after ethanol (as placebo) application. In the style of a balanced placebo trial design, the subjects received during half of the testing the correct information about the applied substance (topical menthol or ethanol) and during half of the testing the incorrect information, leading to four tested conditions (treatment conditions: menthol-told-menthol and menthol-told-ethanol; placebo conditions: ethanol-told-menthol and ethanol-told-ethanol). Cold but not mechanical hyperalgesia was reliably induced by the model. The cold pain threshold decreased in both treatment conditions regardless whether true or false information was given. Minor suggestion effects were found in subjects with prior ethanol application. The menthol model is a reliable, nonsuggestible model to induce cold hyperalgesia. Mechanical hyperalgesia is not as reliable to induce. Cold hyperalgesia may be investigated under unbiased and suggestion-free conditions using the menthol model of pain. © 2018 European Pain Federation - EFIC®.

In-place burning of crude oil in broken ice: 1985 testing at OHMSETT (Oil and Hazardous Materials Simulated Environmental Test Tank)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smith, N.K.; Diaz, A.

1985-08-01

In January and March of 1985, in-place oil burning tests were conducted at the U.S. Environmental Protection Agency's Oil and Hazardous Materials Simulated Environmental Test Tank. (OHMSETT) facility in Leonardo, New Jersey. In-place combustion of Prudhoe Bay and Amauligak crude oil slicks was attempted in varying ice coverages, oil conditions, and ambient conditions. An emulsion of Amauligak crude oil and water was also ignited three times and burned in 80% ice cover, removing nearly 50% of the emulsion.

Virtual reality conditioned place preference using monetary reward

PubMed Central

Childs, Emma; Astur, Robert S.; de Wit, Harriet

2017-01-01

Computerized tasks based on conditioned place preference (CPP) methodology offer the opportunity to study learning mechanisms involved in conditioned reward in humans. In this study, we examined acquisition and extinction of a CPP for virtual environments associated with monetary reward ($). Healthy men and women (N=57) completed a computerized CPP task in which they controlled an avatar within a virtual environment. On day 1, subjects completed 6 conditioning trials in which one room was paired with high $ and another with low $. Acquisition of place conditioning was assessed by measuring the time spent in each room during an exploration test of the virtual environments and using self-reported ratings of room liking and preference. Twenty-four hours later, retention and extinction of CPP were assessed during 4 successive exploration tests of the virtual environments. Participants exhibited a place preference for (spent significantly more time in) the virtual room paired with high $ over the one paired with low $ (p=0.015). They also reported that they preferred the high $ room (p<0.001) and liked it significantly more than the low $ room (p<0.001). However, these preferences were short-lived: 24h later subjects did not exhibit a behavioral or subjective preference for the high $ room. These findings show that individuals exhibit transient behavioral and subjective preferences for a virtual environment paired with monetary reward. Variations on this task may be useful to study mechanisms and brain substrates involved in conditioned reward and to examine the influence of drugs upon appetitive conditioning. PMID:28108321

Long-chain fatty acid combustion rate is associated with unique metabolite profiles in skeletal muscle mitochondria.

PubMed

Seifert, Erin L; Fiehn, Oliver; Bezaire, Véronic; Bickel, David R; Wohlgemuth, Gert; Adams, Sean H; Harper, Mary-Ellen

2010-03-24

Incomplete or limited long-chain fatty acid (LCFA) combustion in skeletal muscle has been associated with insulin resistance. Signals that are responsive to shifts in LCFA beta-oxidation rate or degree of intramitochondrial catabolism are hypothesized to regulate second messenger systems downstream of the insulin receptor. Recent evidence supports a causal link between mitochondrial LCFA combustion in skeletal muscle and insulin resistance. We have used unbiased metabolite profiling of mouse muscle mitochondria with the aim of identifying candidate metabolites within or effluxed from mitochondria and that are shifted with LCFA combustion rate. Large-scale unbiased metabolomics analysis was performed using GC/TOF-MS on buffer and mitochondrial matrix fractions obtained prior to and after 20 min of palmitate catabolism (n = 7 mice/condition). Three palmitate concentrations (2, 9 and 19 microM; corresponding to low, intermediate and high oxidation rates) and 9 microM palmitate plus tricarboxylic acid (TCA) cycle and electron transport chain inhibitors were each tested and compared to zero palmitate control incubations. Paired comparisons of the 0 and 20 min samples were made by Student's t-test. False discovery rate were estimated and Type I error rates assigned. Major metabolite groups were organic acids, amines and amino acids, free fatty acids and sugar phosphates. Palmitate oxidation was associated with unique profiles of metabolites, a subset of which correlated to palmitate oxidation rate. In particular, palmitate oxidation rate was associated with distinct changes in the levels of TCA cycle intermediates within and effluxed from mitochondria. This proof-of-principle study establishes that large-scale metabolomics methods can be applied to organelle-level models to discover metabolite patterns reflective of LCFA combustion, which may lead to identification of molecules linking muscle fat metabolism and insulin signaling. Our results suggest that future studies should focus on the fate of effluxed TCA cycle intermediates and on mechanisms ensuring their replenishment during LCFA metabolism in skeletal muscle.

Long-Chain Fatty Acid Combustion Rate Is Associated with Unique Metabolite Profiles in Skeletal Muscle Mitochondria

PubMed Central

Seifert, Erin L.; Fiehn, Oliver; Bezaire, Véronic; Bickel, David R.; Wohlgemuth, Gert; Adams, Sean H.; Harper, Mary-Ellen

2010-01-01

Background/Aim Incomplete or limited long-chain fatty acid (LCFA) combustion in skeletal muscle has been associated with insulin resistance. Signals that are responsive to shifts in LCFA β-oxidation rate or degree of intramitochondrial catabolism are hypothesized to regulate second messenger systems downstream of the insulin receptor. Recent evidence supports a causal link between mitochondrial LCFA combustion in skeletal muscle and insulin resistance. We have used unbiased metabolite profiling of mouse muscle mitochondria with the aim of identifying candidate metabolites within or effluxed from mitochondria and that are shifted with LCFA combustion rate. Methodology/Principal Findings Large-scale unbiased metabolomics analysis was performed using GC/TOF-MS on buffer and mitochondrial matrix fractions obtained prior to and after 20 min of palmitate catabolism (n = 7 mice/condition). Three palmitate concentrations (2, 9 and 19 µM; corresponding to low, intermediate and high oxidation rates) and 9 µM palmitate plus tricarboxylic acid (TCA) cycle and electron transport chain inhibitors were each tested and compared to zero palmitate control incubations. Paired comparisons of the 0 and 20 min samples were made by Student's t-test. False discovery rate were estimated and Type I error rates assigned. Major metabolite groups were organic acids, amines and amino acids, free fatty acids and sugar phosphates. Palmitate oxidation was associated with unique profiles of metabolites, a subset of which correlated to palmitate oxidation rate. In particular, palmitate oxidation rate was associated with distinct changes in the levels of TCA cycle intermediates within and effluxed from mitochondria. Conclusions/Significance This proof-of-principle study establishes that large-scale metabolomics methods can be applied to organelle-level models to discover metabolite patterns reflective of LCFA combustion, which may lead to identification of molecules linking muscle fat metabolism and insulin signaling. Our results suggest that future studies should focus on the fate of effluxed TCA cycle intermediates and on mechanisms ensuring their replenishment during LCFA metabolism in skeletal muscle. PMID:20352092

Cell shape characterization and classification with discrete Fourier transforms and self-organizing maps.

PubMed

Kriegel, Fabian L; Köhler, Ralf; Bayat-Sarmadi, Jannike; Bayerl, Simon; Hauser, Anja E; Niesner, Raluca; Luch, Andreas; Cseresnyes, Zoltan

2018-03-01

Cells in their natural environment often exhibit complex kinetic behavior and radical adjustments of their shapes. This enables them to accommodate to short- and long-term changes in their surroundings under physiological and pathological conditions. Intravital multi-photon microscopy is a powerful tool to record this complex behavior. Traditionally, cell behavior is characterized by tracking the cells' movements, which yields numerous parameters describing the spatiotemporal characteristics of cells. Cells can be classified according to their tracking behavior using all or a subset of these kinetic parameters. This categorization can be supported by the a priori knowledge of experts. While such an approach provides an excellent starting point for analyzing complex intravital imaging data, faster methods are required for automated and unbiased characterization. In addition to their kinetic behavior, the 3D shape of these cells also provide essential clues about the cells' status and functionality. New approaches that include the study of cell shapes as well may also allow the discovery of correlations amongst the track- and shape-describing parameters. In the current study, we examine the applicability of a set of Fourier components produced by Discrete Fourier Transform (DFT) as a tool for more efficient and less biased classification of complex cell shapes. By carrying out a number of 3D-to-2D projections of surface-rendered cells, the applied method reduces the more complex 3D shape characterization to a series of 2D DFTs. The resulting shape factors are used to train a Self-Organizing Map (SOM), which provides an unbiased estimate for the best clustering of the data, thereby characterizing groups of cells according to their shape. We propose and demonstrate that such shape characterization is a powerful addition to, or a replacement for kinetic analysis. This would make it especially useful in situations where live kinetic imaging is less practical or not possible at all. © 2017 International Society for Advancement of Cytometry. © 2017 International Society for Advancement of Cytometry.

Bias due to differential participation in case-control studies and review of available approaches for adjustment.

PubMed

Aigner, Annette; Grittner, Ulrike; Becher, Heiko

2018-01-01

Low response rates in epidemiologic research potentially lead to the recruitment of a non-representative sample of controls in case-control studies. Problems in the unbiased estimation of odds ratios arise when characteristics causing the probability of participation are associated with exposure and outcome. This is a specific setting of selection bias and a realistic hazard in many case-control studies. This paper formally describes the problem and shows its potential extent, reviews existing approaches for bias adjustment applicable under certain conditions, compares and applies them. We focus on two scenarios: a characteristic C causing differential participation of controls is linked to the outcome through its association with risk factor E (scenario I), and C is additionally a genuine risk factor itself (scenario II). We further assume external data sources are available which provide an unbiased estimate of C in the underlying population. Given these scenarios, we (i) review available approaches and their performance in the setting of bias due to differential participation; (ii) describe two existing approaches to correct for the bias in both scenarios in more detail; (iii) present the magnitude of the resulting bias by simulation if the selection of a non-representative sample is ignored; and (iv) demonstrate the approaches' application via data from a case-control study on stroke. The bias of the effect measure for variable E in scenario I and C in scenario II can be large and should therefore be adjusted for in any analysis. It is positively associated with the difference in response rates between groups of the characteristic causing differential participation, and inversely associated with the total response rate in the controls. Adjustment in a standard logistic regression framework is possible in both scenarios if the population distribution of the characteristic causing differential participation is known or can be approximated well.

Study protocol of the internet user Cohort for Unbiased Recognition of gaming disorder in Early adolescence (iCURE), Korea, 2015–2019

PubMed Central

Jeong, Hyunsuk; Jo, Sun-Jin; Lee, Seung-Yup; Kim, Eunjin; Son, Hye Jung; Han, Hyun-ho; Lee, Hae Kook; Kweon, Yong-Sil; Bhang, Soo-young; Choi, Jung-Seok; Kim, Bung-Nyun; Gentile, Douglas A; Potenza, Marc N

2017-01-01

Introduction In 2013, the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) proposed nine internet gaming disorder (IGD) diagnostic criteria as a condition warranting further empirical and clinical research. The aim of this study is to clarify the natural and clinical courses of IGD proposed DSM-5 in adolescents and to evaluate its risk and protective factors. Methods and analysis The Internet user Cohort for Unbiased Recognition of gaming disorder in Early Adolescence (iCURE) study is an ongoing multidisciplinary, prospective, longitudinal cohort study conducted in 21 schools in Korea. Participant recruitment commenced in March 2015 with the goal of registering 3000 adolescents. The baseline assessment included surveys on emotional, social and environmental characteristics. A parent or guardian completed questionnaires and a structured psychiatric comorbidity diagnostic interview regarding their children. Adolescents with the Internet Game Use-Elicited Symptom Screen total scores of 6 or higher were asked to participate in the clinical diagnostic interview. Two subcohorts of adolescents were constructed: a representative subcohort and a clinical evaluation subcohort. The representative subcohort comprises a randomly selected 10% of the iCURE to investigate the clinical course of IGD based on clinical diagnosis and to estimate the false negative rate. The clinical evaluation subcohort comprised participants meeting three or more of the nine IGD criteria, determined by clinical diagnostic interview, to show the clinical course of IGD. Follow-up data will be collected annually for the 3 years following the baseline assessments. The primary endpoint is 2-year incidence, remission and recurrence rates of IGD. Cross-sectional and longitudinal associations between exposures and outcomes as well as mediation factors will be evaluated. Ethics and dissemination This study is approved by the Institutional Review Board of the Catholic University of Korea. Results will be published in peer-reviewed journals. Trial registration number ClinicalTrials.gov (identifier: NCT02415322). PMID:28982839

Role of Medial Prefrontal Cortex Narp in the Extinction of Morphine Conditioned Place Preference

ERIC Educational Resources Information Center

Blouin, Ashley M.; Han, Sungho; Pearce, Anne M.; Cheng, KaiLun; Lee, JongAh J.; Johnson, Alexander W.; Wang, Chuansong; During, Matthew J.; Holland, Peter C.; Shaham, Yavin; Baraban, Jay M.; Reti, Irving M.

2013-01-01

Narp knockout (KO) mice demonstrate an impaired extinction of morphine conditioned place preference (CPP). Because the medial prefrontal cortex (mPFC) has been implicated in extinction learning, we tested whether Narp cells in this region play a role in the extinction of morphine CPP. We found that intracranial injections of adenoassociated virus…

30 CFR 1206.55 - What are my responsibilities to place production into marketable condition and to market the...

Code of Federal Regulations, 2012 CFR

2012-07-01

... 30 Mineral Resources 3 2012-07-01 2012-07-01 false What are my responsibilities to place production into marketable condition and to market the production? 1206.55 Section 1206.55 Mineral Resources OFFICE OF NATURAL RESOURCES REVENUE, DEPARTMENT OF THE INTERIOR NATURAL RESOURCES REVENUE PRODUCT...

30 CFR 1206.55 - What are my responsibilities to place production into marketable condition and to market the...

Code of Federal Regulations, 2013 CFR

2013-07-01

... 30 Mineral Resources 3 2013-07-01 2013-07-01 false What are my responsibilities to place production into marketable condition and to market the production? 1206.55 Section 1206.55 Mineral Resources OFFICE OF NATURAL RESOURCES REVENUE, DEPARTMENT OF THE INTERIOR NATURAL RESOURCES REVENUE PRODUCT...

30 CFR 1206.55 - What are my responsibilities to place production into marketable condition and to market the...

Code of Federal Regulations, 2014 CFR

2014-07-01

... 30 Mineral Resources 3 2014-07-01 2014-07-01 false What are my responsibilities to place production into marketable condition and to market the production? 1206.55 Section 1206.55 Mineral Resources OFFICE OF NATURAL RESOURCES REVENUE, DEPARTMENT OF THE INTERIOR NATURAL RESOURCES REVENUE PRODUCT...

News Sources on Rhodesia: A Comparative Analysis.

ERIC Educational Resources Information Center

McCoy, Jennifer; Cholawsky, Elizabeth

1982-01-01

Concludes that the "London Times" and the Foreign Broadcast Information Service of the United States government provide both comprehensive and unbiased coverage of events in Rhodesia, while the "New York Times" is less complete and the "Christian Science Monitor" is selective. (FL)

The Battle for Legitimacy: "Jazz" Versus Academia

ERIC Educational Resources Information Center

Baker, David

1973-01-01

Jazz is black music; black man gave this music to the world, and every advancement and major innovation of this music has come from him. This is perhaps the reason that has hindered the unbiased acceptance of jazz into academia. (Author/RJ)

Adolescent delta-9-tetrahydrocannabinol (THC) exposure fails to affect THC-induced place and taste conditioning in adult male rats.

PubMed

Wakeford, Alison G P; Flax, Shaun M; Pomfrey, Rebecca L; Riley, Anthony L

2016-01-01

Adolescent initiation of drug use has been linked to problematic drug taking later in life and may represent an important variable that changes the balance of the rewarding and/or aversive effects of abused drugs which may contribute to abuse vulnerability. The current study examined the effects of adolescent THC exposure on THC-induced place preference (rewarding effects) and taste avoidance (aversive effects) conditioning in adulthood. Forty-six male Sprague-Dawley adolescent rats received eight injections of an intermediate dose of THC (3.2mg/kg) or vehicle. After these injections, animals were allowed to mature and then trained in a combined CTA/CPP procedure in adulthood (PND ~90). Animals were given four trials of conditioning with intervening water-recovery days, a final CPP test and then a one-bottle taste avoidance test. THC induced dose-dependent taste avoidance but did not produce place conditioning. None of these effects was impacted by adolescent THC exposure. Adolescent exposure to THC had no effect on THC taste and place conditioning in adulthood. The failure to see an effect of adolescent exposure was addressed in the context of other research that has assessed exposure of drugs of abuse during adolescence on drug reactivity in adulthood. Copyright © 2015 Elsevier Inc. All rights reserved.

THE EFFECT OF EARLY ENVIRONMENTAL MANIPULATION ON LOCOMOTOR SENSITIVITY AND METHAMPHETAMINE CONDITIONED PLACE PREFERENCE REWARD

PubMed Central

Hensleigh, E.; Pritchard, L. M.

2014-01-01

Early life stress leads to several effects on neurological development, affecting health and well-being later in life. Instances of child abuse and neglect are associated with higher rates of depression, risk taking behavior, and an increased risk of drug abuse later in life. This study used repeated neonatal separation of rat pups as a model of early life stress. Rat pups were either handled and weighed as controls or separated for 180 minutes per day during postnatal days 2-8. In adulthood, male and female rats were tested for methamphetamine conditioned place preference reward and methamphetamine induced locomotor activity. Tissue samples were collected and mRNA was quantified for the norepinephrine transporter in the prefrontal cortex and the dopamine transporter in the nucleus accumbens. Results indicated rats given methamphetamine formed a conditioned place preference, but there was no effect of early separation or sex. Separated males showed heightened methamphetamine-induced locomotor activity, but there was no effect of early separation for females. Overall females were more active than males in response to both saline and methamphetamine. No differences in mRNA levels were observed across any conditions. These results suggest early neonatal separation affects methamphetamine-induced locomotor activity in a sex-dependent manner but has no effects on methamphetamine conditioned place preference. PMID:24713150

Guess LOD approach: sufficient conditions for robustness.

PubMed

Williamson, J A; Amos, C I

1995-01-01

Analysis of genetic linkage between a disease and a marker locus requires specifying a genetic model describing both the inheritance pattern and the gene frequencies of the marker and trait loci. Misspecification of the genetic model is likely for etiologically complex diseases. In previous work we have shown through analytic studies that misspecifying the genetic model for disease inheritance does not lead to excess false-positive evidence for genetic linkage provided the genetic marker alleles of all pedigree members are known, or can be inferred without bias from the data. Here, under various selection or ascertainment schemes we extend these previous results to situations in which the genetic model for the marker locus may be incorrect. We provide sufficient conditions for the asymptotic unbiased estimation of the recombination fraction under the null hypothesis of no linkage, and also conditions for the limiting distribution of the likelihood ratio test for no linkage to be chi-squared. Through simulation studies we document some situations under which asymptotic bias can result when the genetic model is misspecified. Among those situations under which an excess of false-positive evidence for genetic linkage can be generated, the most common is failure to provide accurate estimates of the marker allele frequencies. We show that in most cases false-positive evidence for genetic linkage is unlikely to result solely from the misspecification of the genetic model for disease or trait inheritance.

Doxycycline Inhibits Polarization of Macrophages to the Proangiogenic M2-type and Subsequent Neovascularization*

PubMed Central

He, Lizhi; Marneros, Alexander G.

2014-01-01

Macrophages occur along a continuum of functional states between M1-type polarized macrophages with antiangiogenic and antitumor activity and M2-type polarized macrophages, which have been implicated to promote angiogenesis and tumor growth. Proangiogenic M2-type macrophages promote various pathologic conditions, including choroidal neovascularization in models of neovascular age-related macular degeneration, or certain cancers, such as glioblastoma multiforme. Thus, a potential novel therapeutic approach to target pathological angiogenesis in these conditions would be to inhibit the polarization of macrophages toward the proangiogenic M2-type. However, no pharmacological inhibitors of M2-type macrophage polarization have been identified yet. Here we performed an unbiased pharmacological and small chemical screen to identify drugs that inhibit proangiogenic M2-type macrophage polarization and block pathologic macrophage-driven neovascularization. We identified the well tolerated and commonly used antibiotic doxycycline as a potent inhibitor of M2-type polarization of macrophages. Doxycycline inhibited, in a dose-dependent manner, M2-type polarization of human and bone marrow-derived mouse macrophages without affecting cell viability. Furthermore, doxycycline inhibited M2-type macrophage polarization and subsequent neovascularization in vivo in a laser injury model of choroidal neovascularization. Thus, doxycycline could be used to enhance current antiangiogenic treatment approaches in various conditions that are promoted by proangiogenic M2-type macrophages, including neovascular age-related macular degeneration and certain cancers. PMID:24505138

Mineral Nutritional Yield and Nutrient Density of Locally Adapted Wheat Genotypes under Organic Production

PubMed Central

Moreira-Ascarrunz, Sergio Daniel; Larsson, Hans; Prieto-Linde, Maria Luisa; Johansson, Eva

2016-01-01

The aim of the present investigation was to investigate the nutritional yield, nutrient density, stability, and adaptability of organically produced wheat for sustainable and nutritional high value food production. This study evaluated the nutritional yield of four minerals (Fe, Zn, Cu, and Mg) in 19 wheat genotypes, selected as being locally adapted under organic agriculture conditions. The new metric of nutritional yield was calculated for each genotype and they were evaluated for stability using the Additive Main effects and Multiplicative Interaction (AMMI) stability analysis and for genotypic value, stability, and adaptability using the Best Linear Unbiased Prediction (BLUP procedure). The results indicated that there were genotypes suitable for production under organic agriculture conditions with satisfactory yields (>4000 kg·ha−1). Furthermore, these genotypes showed high nutritional yield and nutrient density for the four minerals studied. Additionally, since these genotypes were stable and adaptable over three environmentally different years, they were designated “balanced genotypes” for the four minerals and for the aforementioned characteristics. Selection and breeding of such “balanced genotypes” may offer an alternative to producing nutritious food under low-input agriculture conditions. Furthermore, the type of evaluation presented here may also be of interest for implementation in research conducted in developing countries, following the objectives of producing enough nutrients for a growing population. PMID:28231184

Amphetamine-induced place preference in humans

PubMed Central

Childs, Emma L.; de Wit, Harriet

2009-01-01

Background The conditioned place preference procedure is a widely used animal model of rewarding drug effects that, to date, has not been tested in humans. In this study, we sought to demonstrate that humans, like non-humans, would exhibit a preference for a place previously associated with amphetamine. Further, we investigated the relationship between conditioned place preference and the mood-altering effects of the drug. Methods Thirty-one healthy individuals participated in a five-session procedure during which they experienced the effects of d-amphetamine (20mg) or placebo on two occasions in two distinctive environments (sessions 1 to 4). One group of subjects (paired group, N=19) received amphetamine consistently in one room and placebo in another room, while a second group (unpaired group, N=12) received amphetamine and placebo without regard to the rooms. During the sessions, participants completed questionnaires to rate their mood. On the fifth session, they rated their preference for the two rooms. Results Individuals in the paired group rated their liking of the amphetamine-paired room significantly higher than the placebo-associated room, while there was no difference between ratings of the two rooms for individuals in the unpaired group. In the paired group, drug liking ratings during the conditioning sessions positively predicted preference for the drug-associated room, whereas reports of amphetamine-induced anxiety and dysphoria negatively predicted room liking scores. Conclusions This study demonstrates that humans, like non-humans, prefer a place associated with amphetamine administration. These findings support the idea that subjective responses to a drug contribute to its ability to establish place conditioning. PMID:19111278

The effects of cocaine, alcohol and cocaine/alcohol combinations in conditioned taste aversion learning.

PubMed

Busse, Gregory D; Verendeev, Andrey; Jones, Jermaine; Riley, Anthony L

2005-09-01

We have recently reported that alcohol attenuates cocaine place preferences. Although the basis for this effect is unknown, alcohol may attenuate cocaine reward by potentiating its aversive effects. To examine this possibility, these experiments assessed the effects of alcohol on cocaine-induced taste aversions under conditions similar to those that resulted in attenuated place preferences. Specifically, Experiments 1 and 2 assessed the effects of alcohol (0.5 g/kg) on taste aversions induced by 20, 30 and 40 mg/kg cocaine. Experiment 3 examined the role of intertrial interval in the effects of alcohol (0.5 g/kg) on cocaine (30 mg/kg) taste aversions. In Experiments 1 and 2, cocaine was effective at conditioning aversions. Alcohol produced no measurable effect. Combining cocaine and alcohol produced no greater aversion than cocaine alone (and, in fact, weakened aversions at the lowest dose of cocaine). In Experiment 3, varying the intertrial interval from 3 days (as in the case of Experiments 1 and 2) to 1 day (a procedure identical to that in which alcohol attenuated cocaine place preferences) resulted in significant alcohol- and cocaine-induced taste aversions. Nonetheless, alcohol remained ineffective in potentiating cocaine aversions. Thus, under these conditions alcohol does not potentiate cocaine's aversiveness. These results were discussed in terms of their implication for the effects of alcohol on cocaine-induced place preferences. Further, the effects of alcohol on place preferences conditioned by cocaine were discussed in relation to other assessments of the effects of alcohol on the affective properties of cocaine and the implications of these interactions for alcohol and cocaine co-use.

NTP-CERHR EXPERT PANEL UPDATE ON THE REPRODUCTIVE AND DEVELOPMENTAL TOXICITY OF DI(2-ETHYLHEXYL) PHTHALATE.

EPA Science Inventory

The purpose of the Center is to provide timely, unbiased, scientifically sound evaluations of human and experimental evidence for adverse effects on reproduction and development caused by agents to which humans may be exposed.

Some Unintended Consequences of "Top Down" Organization Development

ERIC Educational Resources Information Center

White, Bernard J.; Ramsey, V. Jean

1978-01-01

An organizational development consultant is expected to perform a thorough and unbiased diagnosis of the organization's functioning. This is an account of a case study of the effect of top management influence on the consultant's awareness and definition of problems. (Author/MLF)

Minimum variance geographic sampling

NASA Technical Reports Server (NTRS)

Terrell, G. R. (Principal Investigator)

1980-01-01

Resource inventories require samples with geographical scatter, sometimes not as widely spaced as would be hoped. A simple model of correlation over distances is used to create a minimum variance unbiased estimate population means. The fitting procedure is illustrated from data used to estimate Missouri corn acreage.

Nurse Practitioners, Certified Nurse Midwives, and Physician Assistants in Physician Offices

MedlinePlus

... on Vital and Health Statistics Annual Reports Health Survey Research Methods Conference Reports from the National Medical Care ... each sample visit that takes all stages of design into account. The survey data are inflated or weighted to produce unbiased ...

Extending DFT-based genetic algorithms by atom-to-place re-assignment via perturbation theory: A systematic and unbiased approach to structures of mixed-metallic clusters

DOE Office of Scientific and Technical Information (OSTI.GOV)

Weigend, Florian, E-mail: florian.weigend@kit.edu

2014-10-07

Energy surfaces of metal clusters usually show a large variety of local minima. For homo-metallic species the energetically lowest can be found reliably with genetic algorithms, in combination with density functional theory without system-specific parameters. For mixed-metallic clusters this is much more difficult, as for a given arrangement of nuclei one has to find additionally the best of many possibilities of assigning different metal types to the individual positions. In the framework of electronic structure methods this second issue is treatable at comparably low cost at least for elements with similar atomic number by means of first-order perturbation theory, asmore » shown previously [F. Weigend, C. Schrodt, and R. Ahlrichs, J. Chem. Phys. 121, 10380 (2004)]. In the present contribution the extension of a genetic algorithm with the re-assignment of atom types to atom sites is proposed and tested for the search of the global minima of PtHf{sub 12} and [LaPb{sub 7}Bi{sub 7}]{sup 4−}. For both cases the (putative) global minimum is reliably found with the extended technique, which is not the case for the “pure” genetic algorithm.« less

Deterrent effects of demerit points and license sanctions on drivers' traffic law violations using a proportional hazard model.

PubMed

Lee, Jaeyeong; Park, Byung-Jung; Lee, Chungwon

2018-04-01

Current traffic law enforcement places an emphasis on reducing accident risk from human factors such as drunk driving and speeding. Among the various strategies implemented, demerit points and license sanction systems have been widely used as punitive and educational measures. Limitations, however, exist in previous studies in terms of estimating the interaction effects of demerit points and license sanctions. To overcome such limitations, this work focused on identifying the interaction effects of demerit points and license sanctions on driver traffic violation behavior. The interaction deterrent effects were assessed by using a Cox's proportional hazard model to provide a more accurate and unbiased estimation. For this purpose, five years of driver conviction data was obtained from the Korea National Police Agency (KNPA). This data included personal characteristics, demerit point accumulation and license sanction status. The analysis showed that accumulated demerit points had specific deterrent effects. Additionally, license revocation showed consistent and significant deterrent effects, greater than those for suspension. Male drivers under their 30s holding a motorcycle license were identified as the most violation-prone driver group, suggesting that stricter testing for the acquisition of a motorcycle driver's license is needed. Copyright © 2018 Elsevier Ltd. All rights reserved.

Integrating High-Dimensional Transcriptomics and Image Analysis Tools into Early Safety Screening: Proof of Concept for a New Early Drug Development Strategy.

PubMed

Verbist, Bie M P; Verheyen, Geert R; Vervoort, Liesbet; Crabbe, Marjolein; Beerens, Dominiek; Bosmans, Cindy; Jaensch, Steffen; Osselaer, Steven; Talloen, Willem; Van den Wyngaert, Ilse; Van Hecke, Geert; Wuyts, Dirk; Van Goethem, Freddy; Göhlmann, Hinrich W H

2015-10-19

During drug discovery and development, the early identification of adverse effects is expected to reduce costly late-stage failures of candidate drugs. As risk/safety assessment takes place rather late during the development process and due to the limited ability of animal models to predict the human situation, modern unbiased high-dimensional biology readouts are sought, such as molecular signatures predictive for in vivo response using high-throughput cell-based assays. In this theoretical proof of concept, we provide findings of an in-depth exploration of a single chemical core structure. Via transcriptional profiling, we identified a subset of close analogues that commonly downregulate multiple tubulin genes across cellular contexts, suggesting possible spindle poison effects. Confirmation via a qualified toxicity assay (in vitro micronucleus test) and the identification of a characteristic aggregate-formation phenotype via exploratory high-content imaging validated the initial findings. SAR analysis triggered the synthesis of a new set of compounds and allowed us to extend the series showing the genotoxic effect. We demonstrate the potential to flag toxicity issues by utilizing data from exploratory experiments that are typically generated for target evaluation purposes during early drug discovery. We share our thoughts on how this approach may be incorporated into drug development strategies.

Identifying currents in the gene pool for bacterial populations using an integrative approach.

PubMed

Tang, Jing; Hanage, William P; Fraser, Christophe; Corander, Jukka

2009-08-01

The evolution of bacterial populations has recently become considerably better understood due to large-scale sequencing of population samples. It has become clear that DNA sequences from a multitude of genes, as well as a broad sample coverage of a target population, are needed to obtain a relatively unbiased view of its genetic structure and the patterns of ancestry connected to the strains. However, the traditional statistical methods for evolutionary inference, such as phylogenetic analysis, are associated with several difficulties under such an extensive sampling scenario, in particular when a considerable amount of recombination is anticipated to have taken place. To meet the needs of large-scale analyses of population structure for bacteria, we introduce here several statistical tools for the detection and representation of recombination between populations. Also, we introduce a model-based description of the shape of a population in sequence space, in terms of its molecular variability and affinity towards other populations. Extensive real data from the genus Neisseria are utilized to demonstrate the potential of an approach where these population genetic tools are combined with an phylogenetic analysis. The statistical tools introduced here are freely available in BAPS 5.2 software, which can be downloaded from http://web.abo.fi/fak/mnf/mate/jc/software/baps.html.

Perceptual distance and the moon illusion.

PubMed

Kaufman, Lloyd; Vassiliades, Vassias; Noble, Richard; Alexander, Robert; Kaufman, James; Edlund, Stefan

2007-01-01

The elevated moon usually appears smaller than the horizon moon of equal angular size. This is the moon illusion. Distance cues may enable the perceptual system to place the horizon moon at an effectively greater distance than the elevated moon, thus making it appear as larger. This explanation is related to the size-distance invariance hypothesis. However, the larger horizon moon is usually judged as closer than the smaller zenith moon. A bias to expect an apparently large object to be closer than a smaller object may account for this conflict. We designed experiments to determine if unbiased sensitivity to illusory differences in the size and distance of the moon (as measured by d') is consistent with SDIH. A moon above a 'terrain' was compared in both distance and size to an infinitely distant moon in empty space (the reduction moon). At a short distance the terrain moon was adjudged as both closer and smaller than the reduction moon. But these differences could not be detected at somewhat greater distances. At still greater distances the terrain moon was perceived as both more distant and larger than the reduction moon. The distances at which these transitions occurred were essentially the same for both distance and size discrimination tasks, thus supporting SDIH.

Chartbook of Major Indicators: Conditions Placing Children in the South at Risk.

ERIC Educational Resources Information Center

Southern Inst. on Children and Families, Columbia, SC.

Noting that the southern region of the United States is challenged by some of the most difficult and entrenched economic, health, and social problems that place children at risk, this chartbook presents information on indicators of the current status of children and families in the South and contrasts conditions in the South with those in other…

Naloxone attenuates the conditioned place preference induced by wheel running in rats.

PubMed

Lett, B T; Grant, V L; Koh, M T

2001-02-01

Pairings, during which an episode of wheel running is followed by confinement in a distinctive place, produce conditioned place preference (CPP) in rats. This finding indicates that wheel running has a rewarding effect that outlasts the activity itself. In two similar experiments, we tested the hypothesis that this rewarding effect of wheel running is mediated by endogenous opioids. During a paired trial, the rats in the naloxone group were first allowed to wheel run for 2 h, then injected with naloxone (0.5 or 0.1 mg/kg in Experiments 1 and 2, respectively), and 10 min later placed in a distinctive chamber. During an unpaired trial, these rats were confined in an adjoining chamber without wheel running. Naloxone was injected before placement in both chambers, so that if naloxone-induced conditioned place aversion occurred, it would have counteracting effects on performance during the preference test. The rats in the saline group were similarly treated, except that saline was injected instead of naloxone. CPP occurred in the saline group, but not in the naloxone group. Thus, naloxone attenuated the CPP induced by wheel running. This finding supports the hypothesis that the rewarding effect of wheel running is mediated by endogenous opioids.

Unbiased Quantitative Models of Protein Translation Derived from Ribosome Profiling Data

PubMed Central

Gritsenko, Alexey A.; Hulsman, Marc; Reinders, Marcel J. T.; de Ridder, Dick

2015-01-01

Translation of RNA to protein is a core process for any living organism. While for some steps of this process the effect on protein production is understood, a holistic understanding of translation still remains elusive. In silico modelling is a promising approach for elucidating the process of protein synthesis. Although a number of computational models of the process have been proposed, their application is limited by the assumptions they make. Ribosome profiling (RP), a relatively new sequencing-based technique capable of recording snapshots of the locations of actively translating ribosomes, is a promising source of information for deriving unbiased data-driven translation models. However, quantitative analysis of RP data is challenging due to high measurement variance and the inability to discriminate between the number of ribosomes measured on a gene and their speed of translation. We propose a solution in the form of a novel multi-scale interpretation of RP data that allows for deriving models with translation dynamics extracted from the snapshots. We demonstrate the usefulness of this approach by simultaneously determining for the first time per-codon translation elongation and per-gene translation initiation rates of Saccharomyces cerevisiae from RP data for two versions of the Totally Asymmetric Exclusion Process (TASEP) model of translation. We do this in an unbiased fashion, by fitting the models using only RP data with a novel optimization scheme based on Monte Carlo simulation to keep the problem tractable. The fitted models match the data significantly better than existing models and their predictions show better agreement with several independent protein abundance datasets than existing models. Results additionally indicate that the tRNA pool adaptation hypothesis is incomplete, with evidence suggesting that tRNA post-transcriptional modifications and codon context may play a role in determining codon elongation rates. PMID:26275099

Unbiased Quantitative Models of Protein Translation Derived from Ribosome Profiling Data.

PubMed

Gritsenko, Alexey A; Hulsman, Marc; Reinders, Marcel J T; de Ridder, Dick

2015-08-01

Translation of RNA to protein is a core process for any living organism. While for some steps of this process the effect on protein production is understood, a holistic understanding of translation still remains elusive. In silico modelling is a promising approach for elucidating the process of protein synthesis. Although a number of computational models of the process have been proposed, their application is limited by the assumptions they make. Ribosome profiling (RP), a relatively new sequencing-based technique capable of recording snapshots of the locations of actively translating ribosomes, is a promising source of information for deriving unbiased data-driven translation models. However, quantitative analysis of RP data is challenging due to high measurement variance and the inability to discriminate between the number of ribosomes measured on a gene and their speed of translation. We propose a solution in the form of a novel multi-scale interpretation of RP data that allows for deriving models with translation dynamics extracted from the snapshots. We demonstrate the usefulness of this approach by simultaneously determining for the first time per-codon translation elongation and per-gene translation initiation rates of Saccharomyces cerevisiae from RP data for two versions of the Totally Asymmetric Exclusion Process (TASEP) model of translation. We do this in an unbiased fashion, by fitting the models using only RP data with a novel optimization scheme based on Monte Carlo simulation to keep the problem tractable. The fitted models match the data significantly better than existing models and their predictions show better agreement with several independent protein abundance datasets than existing models. Results additionally indicate that the tRNA pool adaptation hypothesis is incomplete, with evidence suggesting that tRNA post-transcriptional modifications and codon context may play a role in determining codon elongation rates.

Unbiased in-depth characterization of CEX fractions from a stressed monoclonal antibody by mass spectrometry

PubMed Central

Griaud, François; Denefeld, Blandine; Lang, Manuel; Hensinger, Héloïse; Haberl, Peter; Berg, Matthias

2017-01-01

ABSTRACT Characterization of charge-based variants by mass spectrometry (MS) is required for the analytical development of a new biologic entity and its marketing approval by health authorities. However, standard peak-based data analysis approaches are time-consuming and biased toward the detection, identification, and quantification of main variants only. The aim of this study was to characterize in-depth acidic and basic species of a stressed IgG1 monoclonal antibody using comprehensive and unbiased MS data evaluation tools. Fractions collected from cation ion exchange (CEX) chromatography were analyzed as intact, after reduction of disulfide bridges, and after proteolytic cleavage using Lys-C. Data of both intact and reduced samples were evaluated consistently using a time-resolved deconvolution algorithm. Peptide mapping data were processed simultaneously, quantified and compared in a systematic manner for all MS signals and fractions. Differences observed between the fractions were then further characterized and assigned. Time-resolved deconvolution enhanced pattern visualization and data interpretation of main and minor modifications in 3-dimensional maps across CEX fractions. Relative quantification of all MS signals across CEX fractions before peptide assignment enabled the detection of fraction-specific chemical modifications at abundances below 1%. Acidic fractions were shown to be heterogeneous, containing antibody fragments, glycated as well as deamidated forms of the heavy and light chains. In contrast, the basic fractions contained mainly modifications of the C-terminus and pyroglutamate formation at the N-terminus of the heavy chain. Systematic data evaluation was performed to investigate multiple data sets and comprehensively extract main and minor differences between each CEX fraction in an unbiased manner. PMID:28379786

Markov state models from short non-equilibrium simulations—Analysis and correction of estimation bias

NASA Astrophysics Data System (ADS)

Nüske, Feliks; Wu, Hao; Prinz, Jan-Hendrik; Wehmeyer, Christoph; Clementi, Cecilia; Noé, Frank

2017-03-01

Many state-of-the-art methods for the thermodynamic and kinetic characterization of large and complex biomolecular systems by simulation rely on ensemble approaches, where data from large numbers of relatively short trajectories are integrated. In this context, Markov state models (MSMs) are extremely popular because they can be used to compute stationary quantities and long-time kinetics from ensembles of short simulations, provided that these short simulations are in "local equilibrium" within the MSM states. However, over the last 15 years since the inception of MSMs, it has been controversially discussed and not yet been answered how deviations from local equilibrium can be detected, whether these deviations induce a practical bias in MSM estimation, and how to correct for them. In this paper, we address these issues: We systematically analyze the estimation of MSMs from short non-equilibrium simulations, and we provide an expression for the error between unbiased transition probabilities and the expected estimate from many short simulations. We show that the unbiased MSM estimate can be obtained even from relatively short non-equilibrium simulations in the limit of long lag times and good discretization. Further, we exploit observable operator model (OOM) theory to derive an unbiased estimator for the MSM transition matrix that corrects for the effect of starting out of equilibrium, even when short lag times are used. Finally, we show how the OOM framework can be used to estimate the exact eigenvalues or relaxation time scales of the system without estimating an MSM transition matrix, which allows us to practically assess the discretization quality of the MSM. Applications to model systems and molecular dynamics simulation data of alanine dipeptide are included for illustration. The improved MSM estimator is implemented in PyEMMA of version 2.3.

Rapid Evolution of Ovarian-Biased Genes in the Yellow Fever Mosquito (Aedes aegypti).

PubMed

Whittle, Carrie A; Extavour, Cassandra G

2017-08-01

Males and females exhibit highly dimorphic phenotypes, particularly in their gonads, which is believed to be driven largely by differential gene expression. Typically, the protein sequences of genes upregulated in males, or male-biased genes, evolve rapidly as compared to female-biased and unbiased genes. To date, the specific study of gonad-biased genes remains uncommon in metazoans. Here, we identified and studied a total of 2927, 2013, and 4449 coding sequences (CDS) with ovary-biased, testis-biased, and unbiased expression, respectively, in the yellow fever mosquito Aedes aegypti The results showed that ovary-biased and unbiased CDS had higher nonsynonymous to synonymous substitution rates (dN/dS) and lower optimal codon usage (those codons that promote efficient translation) than testis-biased genes. Further, we observed higher dN/dS in ovary-biased genes than in testis-biased genes, even for genes coexpressed in nonsexual (embryo) tissues. Ovary-specific genes evolved exceptionally fast, as compared to testis- or embryo-specific genes, and exhibited higher frequency of positive selection. Genes with ovary expression were preferentially involved in olfactory binding and reception. We hypothesize that at least two potential mechanisms could explain rapid evolution of ovary-biased genes in this mosquito: (1) the evolutionary rate of ovary-biased genes may be accelerated by sexual selection (including female-female competition or male-mate choice) affecting olfactory genes during female swarming by males, and/or by adaptive evolution of olfactory signaling within the female reproductive system ( e.g. , sperm-ovary signaling); and/or (2) testis-biased genes may exhibit decelerated evolutionary rates due to the formation of mating plugs in the female after copulation, which limits male-male sperm competition. Copyright © 2017 by the Genetics Society of America.

Validation of abundance estimates from mark–recapture and removal techniques for rainbow trout captured by electrofishing in small streams

USGS Publications Warehouse

Rosenberger, Amanda E.; Dunham, Jason B.

2005-01-01

Estimation of fish abundance in streams using the removal model or the Lincoln - Peterson mark - recapture model is a common practice in fisheries. These models produce misleading results if their assumptions are violated. We evaluated the assumptions of these two models via electrofishing of rainbow trout Oncorhynchus mykiss in central Idaho streams. For one-, two-, three-, and four-pass sampling effort in closed sites, we evaluated the influences of fish size and habitat characteristics on sampling efficiency and the accuracy of removal abundance estimates. We also examined the use of models to generate unbiased estimates of fish abundance through adjustment of total catch or biased removal estimates. Our results suggested that the assumptions of the mark - recapture model were satisfied and that abundance estimates based on this approach were unbiased. In contrast, the removal model assumptions were not met. Decreasing sampling efficiencies over removal passes resulted in underestimated population sizes and overestimates of sampling efficiency. This bias decreased, but was not eliminated, with increased sampling effort. Biased removal estimates based on different levels of effort were highly correlated with each other but were less correlated with unbiased mark - recapture estimates. Stream size decreased sampling efficiency, and stream size and instream wood increased the negative bias of removal estimates. We found that reliable estimates of population abundance could be obtained from models of sampling efficiency for different levels of effort. Validation of abundance estimates requires extra attention to routine sampling considerations but can help fisheries biologists avoid pitfalls associated with biased data and facilitate standardized comparisons among studies that employ different sampling methods.

Unbiased Scanning Method and Data Banking Approach Using Ultra-High Performance Liquid Chromatography Coupled with High-Resolution Mass Spectrometry for Quantitative Comparison of Metabolite Exposure in Plasma across Species Analyzed at Different Dates.

PubMed

Gao, Hongying; Deng, Shibing; Obach, R Scott

2015-12-01

An unbiased scanning methodology using ultra high-performance liquid chromatography coupled with high-resolution mass spectrometry was used to bank data and plasma samples for comparing the data generated at different dates. This method was applied to bank the data generated earlier in animal samples and then to compare the exposure to metabolites in animal versus human for safety assessment. With neither authentic standards nor prior knowledge of the identities and structures of metabolites, full scans for precursor ions and all ion fragments (AIF) were employed with a generic gradient LC method to analyze plasma samples at positive and negative polarity, respectively. In a total of 22 tested drugs and metabolites, 21 analytes were detected using this unbiased scanning method except that naproxen was not detected due to low sensitivity at negative polarity and interference at positive polarity; and 4'- or 5-hydroxy diclofenac was not separated by a generic UPLC method. Statistical analysis of the peak area ratios of the analytes versus the internal standard in five repetitive analyses over approximately 1 year demonstrated that the analysis variation was significantly different from sample instability. The confidence limits for comparing the exposure using peak area ratio of metabolites in animal plasma versus human plasma measured over approximately 1 year apart were comparable to the analysis undertaken side by side on the same days. These statistical analysis results showed it was feasible to compare data generated at different dates with neither authentic standards nor prior knowledge of the analytes.

Density estimation in wildlife surveys

USGS Publications Warehouse

Bart, Jonathan; Droege, Sam; Geissler, Paul E.; Peterjohn, Bruce G.; Ralph, C. John

2004-01-01

Several authors have recently discussed the problems with using index methods to estimate trends in population size. Some have expressed the view that index methods should virtually never be used. Others have responded by defending index methods and questioning whether better alternatives exist. We suggest that index methods are often a cost-effective component of valid wildlife monitoring but that double-sampling or another procedure that corrects for bias or establishes bounds on bias is essential. The common assertion that index methods require constant detection rates for trend estimation is mathematically incorrect; the requirement is no long-term trend in detection "ratios" (index result/parameter of interest), a requirement that is probably approximately met by many well-designed index surveys. We urge that more attention be given to defining bird density rigorously and in ways useful to managers. Once this is done, 4 sources of bias in density estimates may be distinguished: coverage, closure, surplus birds, and detection rates. Distance, double-observer, and removal methods do not reduce bias due to coverage, closure, or surplus birds. These methods may yield unbiased estimates of the number of birds present at the time of the survey, but only if their required assumptions are met, which we doubt occurs very often in practice. Double-sampling, in contrast, produces unbiased density estimates if the plots are randomly selected and estimates on the intensive surveys are unbiased. More work is needed, however, to determine the feasibility of double-sampling in different populations and habitats. We believe the tension that has developed over appropriate survey methods can best be resolved through increased appreciation of the mathematical aspects of indices, especially the effects of bias, and through studies in which candidate methods are evaluated against known numbers determined through intensive surveys.

Fatal Powassan Encephalitis (Deer Tick Virus, Lineage II) in a Patient With Fever and Orchitis Receiving Rituximab.

PubMed

Solomon, Isaac H; Spera, Kristyn M; Ryan, Sophia L; Helgager, Jeffrey; Andrici, Juliana; Zaki, Sherif R; Vaitkevicius, Henrikas; Leon, Kristoffer E; Wilson, Michael R; DeRisi, Joseph L; Koo, Sophia; Smirnakis, Stelios M; De Girolami, Umberto

2018-06-01

Powassan virus is a rare but increasingly recognized cause of severe neurological disease. To highlight the diagnostic challenges and neuropathological findings in a fatal case of Powassan encephalitis caused by deer tick virus (lineage II) in a patient with follicular lymphoma receiving rituximab, with nonspecific anti-GAD65 antibodies, who was initially seen with fever and orchiepididymitis. Comparison of clinical, radiological, histological, and laboratory findings, including immunohistochemistry, real-time polymerase chain reaction, antibody detection, and unbiased sequencing assays, in a single case report (first seen in December 2016) at an academic medical center. Infection with Powassan virus. Results of individual assays compared retrospectively. In a 63-year-old man with fatal Powassan encephalitis, serum and cerebrospinal fluid IgM antibodies were not detected via standard methods, likely because of rituximab exposure. Neuropathological findings were extensive, including diffuse leptomeningeal and parenchymal lymphohistiocytic infiltration, microglial proliferation, marked neuronal loss, and white matter microinfarctions most severely involving the cerebellum, thalamus, and basal ganglia. Diagnosis was made after death by 3 independent methods, including demonstration of Powassan virus antigen in brain biopsy and autopsy tissue, detection of viral RNA in serum and cerebrospinal fluid by targeted real-time polymerase chain reaction, and detection of viral RNA in cerebrospinal fluid by unbiased sequencing. Extensive testing for other etiologies yielded negative results, including mumps virus owing to prodromal orchiepididymitis. Low-titer anti-GAD65 antibodies identified in serum, suggestive of limbic encephalitis, were not detected in cerebrospinal fluid. Owing to the rarity of Powassan encephalitis, a high degree of suspicion is required to make the diagnosis, particularly in an immunocompromised patient, in whom antibody-based assays may be falsely negative. Unbiased sequencing assays have the potential to detect uncommon infectious agents and may prove useful in similar scenarios.

Effects of psilocybin on hippocampal neurogenesis and extinction of trace fear conditioning.

PubMed

Catlow, Briony J; Song, Shijie; Paredes, Daniel A; Kirstein, Cheryl L; Sanchez-Ramos, Juan

2013-08-01

Drugs that modulate serotonin (5-HT) synaptic concentrations impact neurogenesis and hippocampal (HPC)-dependent learning. The primary objective is to determine the extent to which psilocybin (PSOP) modulates neurogenesis and thereby affects acquisition and extinction of HPC-dependent trace fear conditioning. PSOP, the 5-HT2A agonist 25I-NBMeO and the 5-HT2A/C antagonist ketanserin were administered via an acute intraperitoneal injection to mice. Trace fear conditioning was measured as the amount of time spent immobile in the presence of the conditioned stimulus (CS, auditory tone), trace (silent interval) and post-trace interval over 10 trials. Extinction was determined by the number of trials required to resume mobility during CS, trace and post-trace when the shock was not delivered. Neurogenesis was determined by unbiased counts of cells in the dentate gyrus of the HPC birth-dated with BrdU co-expressing a neuronal marker. Mice treated with a range of doses of PSOP acquired a robust conditioned fear response. Mice injected with low doses of PSOP extinguished cued fear conditioning significantly more rapidly than high-dose PSOP or saline-treated mice. Injection of PSOP, 25I-NBMeO or ketanserin resulted in significant dose-dependent decreases in number of newborn neurons in hippocampus. At the low doses of PSOP that enhanced extinction, neurogenesis was not decreased, but rather tended toward an increase. Extinction of "fear conditioning" may be mediated by actions of the drugs at sites other than hippocampus such as the amygdala, which is known to mediate the perception of fear. Another caveat is that PSOP is not purely selective for 5-HT2A receptors. PSOP facilitates extinction of the classically conditioned fear response, and this, and similar agents, should be explored as potential treatments for post-traumatic stress disorder and related conditions.

Virtual reality conditioned place preference using monetary reward.

PubMed

Childs, Emma; Astur, Robert S; de Wit, Harriet

2017-03-30

Computerized tasks based on conditioned place preference (CPP) methodology offer the opportunity to study learning mechanisms involved in conditioned reward in humans. In this study, we examined acquisition and extinction of a CPP for virtual environments associated with monetary reward ($). Healthy men and women (N=57) completed a computerized CPP task in which they controlled an avatar within a virtual environment. On day 1, subjects completed 6 conditioning trials in which one room was paired with high $ and another with low $. Acquisition of place conditioning was assessed by measuring the time spent in each room during an exploration test of the virtual environments and using self-reported ratings of room liking and preference. Twenty-four hours later, retention and extinction of CPP were assessed during 4 successive exploration tests of the virtual environments. Participants exhibited a place preference for (spent significantly more time in) the virtual room paired with high $ over the one paired with low $ (p=0.015). They also reported that they preferred the high $ room (p<0.001) and liked it significantly more than the low $ room (p<0.001). However, these preferences were short-lived: 24h later subjects did not exhibit a behavioral or subjective preference for the high $ room. These findings show that individuals exhibit transient behavioral and subjective preferences for a virtual environment paired with monetary reward. Variations on this task may be useful to study mechanisms and brain substrates involved in conditioned reward and to examine the influence of drugs upon appetitive conditioning. Copyright © 2017 Elsevier B.V. All rights reserved.

May Exercise Prevent Addiction?

PubMed Central

Fontes-Ribeiro, C. A; Marques, E; Pereira, F. C; Silva, A. P; Macedo, T. R. A

2011-01-01

Amphetamines exert their persistent addictive effects by activating brain's reward pathways, perhaps through the release of dopamine in the nucleus accumbens (and/or in other places). On the other hand, there is a relationship between dopamine and all behavioural aspects that involve motor activity and it has been demonstrated that exercise leads to an increase in the synthesis and release of dopamine, stimulates neuroplasticity and promotes feelings of well-being. Moreover, exercise and drugs of abuse activate overlapping neural systems. Thus, our aim was to study the influence of chronic exercise in the mechanism of addiction using an amphetamine-induced conditioned-place-preference in rats. Adult male Sprague-Dawley rats were randomly separated in groups with and without chronic exercise. Chronic exercise consisted in a 8 week treadmill running program, with increasing intensity. The conditioned place preference test was performed in both groups using a procedure and apparatus previously established. A 2 mg.kg-1 amphetamine or saline solution was administered intraperitonially according to the schedule of the conditioned place preference. Before conditioning none of the animals showed preference for a specific compartment of the apparatus. The used amphetamine dose in the conditioning phase was able to produce a marked preference towards the drug-associated compartment in the group without exercise. In the animals with exercise a significant preference by the compartment associated with saline was observed. These results lead us to conclude that a previous practice of regular physical activity may help preventing amphetamine addiction in the conditions used in this test. PMID:21886560

Brain nicotinic acetylcholine receptors are involved in stress-induced potentiation of nicotine reward in rats.

PubMed

Javadi, Parastoo; Rezayof, Ameneh; Sardari, Maryam; Ghasemzadeh, Zahra

2017-07-01

The aim of the present study was to examine the possible role of nicotinic acetylcholine receptors of the dorsal hippocampus (CA1 regions), the medial prefrontal cortex or the basolateral amygdala in the effect of acute or sub-chronic stress on nicotine-induced conditioned place preference. Our results indicated that subcutaneous administration of nicotine (0.2 mg/kg) induced significant conditioned place preference. Exposure to acute or sub-chronic elevated platform stress potentiated the response of an ineffective dose of nicotine. Pre-conditioning intra-CA1 (0.5-4 µg/rat) or intra-medial prefrontal cortex (0.2-0.3 µg/rat) microinjection of mecamylamine (a non-selective nicotinic acetylcholine receptor antagonist) reversed acute stress-induced potentiation of nicotine reward as measured in the conditioned place preference paradigm. By contrast, pre-conditioning intra-basolateral amygdala microinjection of mecamylamine (4 µg/rat) potentiated the effects of acute stress on nicotine reward. Our findings also showed that intra-CA1 or intra-medial prefrontal cortex, but not intra-basolateral amygdala, microinjection of mecamylamine (4 µg/rat) prevented the effect of sub-chronic stress on nicotine reward. These findings suggest that exposure to elevated platform stress potentiates the rewarding effect of nicotine which may be associated with the involvement of nicotinic acetylcholine receptors. It seems that there is a different contribution of the basolateral amygdala, the medial prefrontal cortex or the CA1 nicotinic acetylcholine receptors in stress-induced potentiation of nicotine-induced conditioned place preference.

Stay or Migrate? An Empirical Study of the Relationship between Place of Work, Place of Study and Birthplace

ERIC Educational Resources Information Center

Liping, Ma; Kunfeng, Pan

2014-01-01

Based on a 2009 national survey on college graduate employment in China, this article analyzes the relationship of college graduates' place of work to their birthplace and where they attend college, using a conditional logit model. The findings indicate that graduates tend to stay to work in their birthplaces or places of study, controlling for…

30 CFR 56.18002 - Examination of working places.

Code of Federal Regulations, 2010 CFR

2010-07-01

... examine each working place at least once each shift for conditions which may adversely affect safety or... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Examination of working places. 56.18002 Section 56.18002 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND...

30 CFR 57.18002 - Examination of working places.

Code of Federal Regulations, 2010 CFR

2010-07-01

... designated by the operator shall examine each working place at least once each shift for conditions which may... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Examination of working places. 57.18002 Section 57.18002 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND...

Evaluation of the installation and initial condition of hydraulic cement concrete overlays placed on three pavements in Virginia.

DOT National Transportation Integrated Search

1999-04-01

Hydraulic cement concrete pavement overlays were placed in the summer of 1995 at the following locations in Virginia: : 1-295 near Richmond : 1-85 near Petersburg : Rt. 29 near Charlottesville. : Overlays were placed on 1-295 SBL (near mi...

Drinking Water

MedlinePlus

... safest water supplies in the world, but drinking water quality can vary from place to place. It depends on the condition of the source water and the treatment it receives. Treatment may include ...

Lineup Administrator Influences on Eyewitness Identification Decisions

ERIC Educational Resources Information Center

Clark, Steven E.; Marshall, Tanya E.; Rosenthal, Robert

2009-01-01

The present research examines how a lineup administrator may influence eyewitness identification decisions through different forms of influence, after providing the witness with standard, unbiased instructions. Participant-witnesses viewed a staged crime and were later shown a target-present or target-absent lineup. The lineup administrators…

The Problem of Biased Data and Potential Solutions for Environmental Assessments

EPA Science Inventory

The utility and credibility of environmental assessments depend on the use of unbiased data. However, it is increasingly clear that, despite peer review, much of the scientific literature is biased. Sources of bias include fraud, publication bias, research designs, funding bias...

How to Hire Fund-Raising Counsel.

ERIC Educational Resources Information Center

Hayes, Joanne

1991-01-01

As objective outsiders, consultants can bring a fresh and unbiased view to institutional needs and perspectives. However, careful preliminary screening of consulting firms by colleges and universities considering their use is important, addressing a variety of cost considerations; prospective firms' experience and success record; and the specific…

A sampling strategy to estimate the area and perimeter of irregularly shaped planar regions

Treesearch

Timothy G. Gregoire; Harry T. Valentine

1995-01-01

The length of a randomly oriented ray emanating from an interior point of a planar region can be used to unbiasedly estimate the region's area and perimeter. Estimators and corresponding variance estimators under various selection strategies are presented.

47 CFR 52.13 - North American Numbering Plan Administrator.

Code of Federal Regulations, 2012 CFR

2012-10-01

... North American Numbering Plan Administrator (NANPA) shall be an independent and impartial non-government... section. It shall assign and administer NANP resources in an efficient, effective, fair, unbiased, and non... additional functions, including but not limited to: (1) Ensuring the efficient and effective administration...

47 CFR 52.13 - North American Numbering Plan Administrator.

Code of Federal Regulations, 2011 CFR

2011-10-01

... North American Numbering Plan Administrator (NANPA) shall be an independent and impartial non-government... section. It shall assign and administer NANP resources in an efficient, effective, fair, unbiased, and non... additional functions, including but not limited to: (1) Ensuring the efficient and effective administration...

47 CFR 52.13 - North American Numbering Plan Administrator.

Code of Federal Regulations, 2014 CFR

2014-10-01

... North American Numbering Plan Administrator (NANPA) shall be an independent and impartial non-government... section. It shall assign and administer NANP resources in an efficient, effective, fair, unbiased, and non... additional functions, including but not limited to: (1) Ensuring the efficient and effective administration...

47 CFR 52.13 - North American Numbering Plan Administrator.

Code of Federal Regulations, 2013 CFR

2013-10-01

... North American Numbering Plan Administrator (NANPA) shall be an independent and impartial non-government... section. It shall assign and administer NANP resources in an efficient, effective, fair, unbiased, and non... additional functions, including but not limited to: (1) Ensuring the efficient and effective administration...

Roofing: Don't Let What's Over Head Kill Your Bottom Line.

ERIC Educational Resources Information Center

Shannon, James W., Jr.

1983-01-01

A Colorado school district employs a professional consulting firm to give an unbiased opinion on the district's roofing needs. Built-up, single-ply, and modified asphalt roofing systems have all been utilized. Preventive maintenance keeps roofing bills to a minimum. (MLF)

Iowa crop variety yield testing: A history and annotated bibliography

USDA-ARS?s Scientific Manuscript database

Variety testing by U.S. agricultural universities, often in cooperation with experiment stations, and professional crop associations is recognized as an independent, unbiased validation of the viability of commercial crop varieties. In Iowa, variety testing has also been conducted by many private ag...

Unbiased reduced density matrices and electronic properties from full configuration interaction quantum Monte Carlo.

PubMed

Overy, Catherine; Booth, George H; Blunt, N S; Shepherd, James J; Cleland, Deidre; Alavi, Ali

2014-12-28

Properties that are necessarily formulated within pure (symmetric) expectation values are difficult to calculate for projector quantum Monte Carlo approaches, but are critical in order to compute many of the important observable properties of electronic systems. Here, we investigate an approach for the sampling of unbiased reduced density matrices within the full configuration interaction quantum Monte Carlo dynamic, which requires only small computational overheads. This is achieved via an independent replica population of walkers in the dynamic, sampled alongside the original population. The resulting reduced density matrices are free from systematic error (beyond those present via constraints on the dynamic itself) and can be used to compute a variety of expectation values and properties, with rapid convergence to an exact limit. A quasi-variational energy estimate derived from these density matrices is proposed as an accurate alternative to the projected estimator for multiconfigurational wavefunctions, while its variational property could potentially lend itself to accurate extrapolation approaches in larger systems.

Unbiased Rare Event Sampling in Spatial Stochastic Systems Biology Models Using a Weighted Ensemble of Trajectories

PubMed Central

Donovan, Rory M.; Tapia, Jose-Juan; Sullivan, Devin P.; Faeder, James R.; Murphy, Robert F.; Dittrich, Markus; Zuckerman, Daniel M.

2016-01-01

The long-term goal of connecting scales in biological simulation can be facilitated by scale-agnostic methods. We demonstrate that the weighted ensemble (WE) strategy, initially developed for molecular simulations, applies effectively to spatially resolved cell-scale simulations. The WE approach runs an ensemble of parallel trajectories with assigned weights and uses a statistical resampling strategy of replicating and pruning trajectories to focus computational effort on difficult-to-sample regions. The method can also generate unbiased estimates of non-equilibrium and equilibrium observables, sometimes with significantly less aggregate computing time than would be possible using standard parallelization. Here, we use WE to orchestrate particle-based kinetic Monte Carlo simulations, which include spatial geometry (e.g., of organelles, plasma membrane) and biochemical interactions among mobile molecular species. We study a series of models exhibiting spatial, temporal and biochemical complexity and show that although WE has important limitations, it can achieve performance significantly exceeding standard parallel simulation—by orders of magnitude for some observables. PMID:26845334

Hetero-type dual photoanodes for unbiased solar water splitting with extended light harvesting

PubMed Central

Kim, Jin Hyun; Jang, Ji-Wook; Jo, Yim Hyun; Abdi, Fatwa F.; Lee, Young Hye; van de Krol, Roel; Lee, Jae Sung

2016-01-01

Metal oxide semiconductors are promising photoelectrode materials for solar water splitting due to their robustness in aqueous solutions and low cost. Yet, their solar-to-hydrogen conversion efficiencies are still not high enough for practical applications. Here we present a strategy to enhance the efficiency of metal oxides, hetero-type dual photoelectrodes, in which two photoanodes of different bandgaps are connected in parallel for extended light harvesting. Thus, a photoelectrochemical device made of modified BiVO4 and α-Fe2O3 as dual photoanodes utilizes visible light up to 610 nm for water splitting, and shows stable photocurrents of 7.0±0.2 mA cm−2 at 1.23 VRHE under 1 sun irradiation. A tandem cell composed with the dual photoanodes–silicon solar cell demonstrates unbiased water splitting efficiency of 7.7%. These results and concept represent a significant step forward en route to the goal of >10% efficiency required for practical solar hydrogen production. PMID:27966548

Geophysical Interpretation of Venus Gravity Data

NASA Technical Reports Server (NTRS)

Reasenberg, R. D.

1985-01-01

The subsurface distribution of Venus was investigated through the analysis of the data from Pioneer Venus Orbiter (PVO). In particular, the Doppler tracking data were used to map the gravitational potential. These were compared to the topographic data from the PVO radar (ORAD). In order to obtain an unbiased comparison, the topography data obtained from the PVO-ORAD were filtered to introduce distortions which are the same as those of the gravity models. Both the gravity and filtered topography maps are derived by two stage processes with a common second stage. In the first stage, the topography was used to calculate a corresponding spacecraft acceleration under the assumptions that the topography has a uniform given density and no compensation. In the second stage, the acceleration measures found in the first stage were passed through a linear inverter to yield maps of gravity and topography. Because these maps are the result of the same inversion process, they contain the same distortion; a comparison between them is unbiased to first order.

Grand canonical validation of the bipartite international trade network.

PubMed

Straka, Mika J; Caldarelli, Guido; Saracco, Fabio

2017-08-01

Devising strategies for economic development in a globally competitive landscape requires a solid and unbiased understanding of countries' technological advancements and similarities among export products. Both can be addressed through the bipartite representation of the International Trade Network. In this paper, we apply the recently proposed grand canonical projection algorithm to uncover country and product communities. Contrary to past endeavors, our methodology, based on information theory, creates monopartite projections in an unbiased and analytically tractable way. Single links between countries or products represent statistically significant signals, which are not accounted for by null models such as the bipartite configuration model. We find stable country communities reflecting the socioeconomic distinction in developed, newly industrialized, and developing countries. Furthermore, we observe product clusters based on the aforementioned country groups. Our analysis reveals the existence of a complicated structure in the bipartite International Trade Network: apart from the diversification of export baskets from the most basic to the most exclusive products, we observe a statistically significant signal of an export specialization mechanism towards more sophisticated products.

Grand canonical validation of the bipartite international trade network

NASA Astrophysics Data System (ADS)

Straka, Mika J.; Caldarelli, Guido; Saracco, Fabio

2017-08-01

Devising strategies for economic development in a globally competitive landscape requires a solid and unbiased understanding of countries' technological advancements and similarities among export products. Both can be addressed through the bipartite representation of the International Trade Network. In this paper, we apply the recently proposed grand canonical projection algorithm to uncover country and product communities. Contrary to past endeavors, our methodology, based on information theory, creates monopartite projections in an unbiased and analytically tractable way. Single links between countries or products represent statistically significant signals, which are not accounted for by null models such as the bipartite configuration model. We find stable country communities reflecting the socioeconomic distinction in developed, newly industrialized, and developing countries. Furthermore, we observe product clusters based on the aforementioned country groups. Our analysis reveals the existence of a complicated structure in the bipartite International Trade Network: apart from the diversification of export baskets from the most basic to the most exclusive products, we observe a statistically significant signal of an export specialization mechanism towards more sophisticated products.

An unbiased risk estimator for image denoising in the presence of mixed poisson-gaussian noise.

PubMed

Le Montagner, Yoann; Angelini, Elsa D; Olivo-Marin, Jean-Christophe

2014-03-01

The behavior and performance of denoising algorithms are governed by one or several parameters, whose optimal settings depend on the content of the processed image and the characteristics of the noise, and are generally designed to minimize the mean squared error (MSE) between the denoised image returned by the algorithm and a virtual ground truth. In this paper, we introduce a new Poisson-Gaussian unbiased risk estimator (PG-URE) of the MSE applicable to a mixed Poisson-Gaussian noise model that unifies the widely used Gaussian and Poisson noise models in fluorescence bioimaging applications. We propose a stochastic methodology to evaluate this estimator in the case when little is known about the internal machinery of the considered denoising algorithm, and we analyze both theoretically and empirically the characteristics of the PG-URE estimator. Finally, we evaluate the PG-URE-driven parametrization for three standard denoising algorithms, with and without variance stabilizing transforms, and different characteristics of the Poisson-Gaussian noise mixture.