XMRV Discovery and Prostate Cancer-Related Research

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David E. Kang

2011-01-01

Full Text Available Xenotropic murine leukemia virus-related virus (XMRV was first reported in 2006 in a study of human prostate cancer patients with genetic variants of the antiviral enzyme, RNase L. Subsequent investigations in North America, Europe, Asia, and Africa have either observed or failed to detect XMRV in patients (prostate cancer, chronic fatigue syndrome-myalgic encephalomyelitis (CFS-ME, and immunosuppressed with respiratory tract infections or normal, healthy, control individuals. The principal confounding factors are the near ubiquitous presence of mouse-derived reagents, antibodies and cells, and often XMRV itself, in laboratories. XMRV infects and replicates well in many human cell lines, but especially in certain prostate cancer cell lines. XMRV also traffics to prostate in a nonhuman primate model of infection. Here, we will review the discovery of XMRV and then focus on prostate cancer-related research involving this intriguing virus.

Toward a clinic of temporality?

Science.gov (United States)

Rivasseau Jonveaux, Thérèse; Batt, Martine; Trognon, Alain

2017-12-01

The discovery of time cells has expanded our knowledge in the field of spatial and temporal information coding and the key role of the hippocampus. The internal clock model complemented with the attentional gate model allows a more in-depth understanding of the perception of time. The motor representation of duration is ensured by the basal ganglia, while the cerebellum synchronizes short duration for the movement. The right prefrontal cortex seemingly intervenes in the handling of temporal information in working memory. The temporal lobe ensures the comparison of durations, especially the right lobe for the reference durations and the medial lobe for the reproduction of durations in episodic memory. During normal aging, the hypothesis of slowing of the temporal processor is evoked when noting the perception of the acceleration of the passage of time that seemingly occurs with advancing age. The various studies pertaining specifically to time cognition, albeit heterogeneous in terms of methodology, attest to the wide-ranging disturbances of this cognitive field during the course of numerous disorders, whether psychiatric - depression and schizophrenia notably - or neurological. Hence, perturbations in temporality are observed in focal brain lesions and in subcortical disorders, such as Parkinson's disease or Huntington's chorea. Alzheimer's disease represents a particularly fertile field of exploration with regard to time cognition and temporality. The objectified deconstruction of temporal experience provides insights into the very processes of temporality and their nature: episodic, semantic and procedural. In addition to exploration based on elementary stimuli, one should also consider the time lived, i.e. that of the subject, to better understand cognition as it relates to time. While the temporal dimension permeates the whole cognitive field, it remains largely neglected: integration of a genuine time cognition and temporality clinic in daily practice remains

Discovery Mondays - “Relativity Theory... strange! Did you say strange?”

CERN Multimedia

2005-01-01

We all know that famous equation E=mc2, but do you know its true significance? Relativity theory: what is the meaning of this strange concept which plunged the physics world into turmoil 100 years ago? What effects can be observed today? Did you know that the GPS system would not work if relativity was not taken into account? The next Discovery Monday will take you on a journey into a strange world. You will be able to witness for yourselves the consequences of Einstein's theories. How, for example, can relativity theory be tested by eclipses? What consequences does it have for the accelerators at CERN? How can it be used to measure the mass of enormous black holes? And finally, how is it linked to the puzzle surrounding the missing mass of the Universe? As part of the World Year of Physics, the next Discovery Monday will be dedicated to one of the theories that Einstein published in 1905, his “annus mirabilis”. Join us at the Microcosm (Reception Building 33, Meyrin site), on Monday 5th September ...

Discovery Mondays - “Relativity Theory... strange! Did you say strange?”

CERN Multimedia

2005-01-01

We all know that famous equation E=mc2, but do you know its true significance? Relativity theory: what is the meaning of this strange concept which plunged the physics world into turmoil 100 years ago? What effects can be observed today? Did you know that the GPS system would not work if relativity was not taken into account? The next Discovery Monday will take you on a journey into a strange world. You will be able to witness for yourselves the consequences of Einstein's theories. How, for example, can relativity theory be tested by eclipses? What consequences does it have for the accelerators at CERN? How can it be used to measure the mass of enormous black holes? And finally, how is it linked to the puzzle surrounding the missing mass of the Universe? As part of the World Year of Physics, the next Discovery Monday will be dedicated to one of the theories that Einstein published in 1905, his “annus mirabilis”. Join us at the Microcosm (Reception Building 33, Meyrin site), on Monday 5th Septemb...

Automatic temporal expectancy: a high-density event-related potential study.

Directory of Open Access Journals (Sweden)

Giovanni Mento

Full Text Available How we compute time is not fully understood. Questions include whether an automatic brain mechanism is engaged in temporally regular environmental structure in order to anticipate events, and whether this can be dissociated from task-related processes, including response preparation, selection and execution. To investigate these issues, a passive temporal oddball task requiring neither time-based motor response nor explicit decision was specifically designed and delivered to participants during high-density, event-related potentials recording. Participants were presented with pairs of audiovisual stimuli (S1 and S2 interspersed with an Inter-Stimulus Interval (ISI that was manipulated according to an oddball probabilistic distribution. In the standard condition (70% of trials, the ISI lasted 1,500 ms, while in the two alternative, deviant conditions (15% each, it lasted 2,500 and 3,000 ms. The passive over-exposition to the standard ISI drove participants to automatically and progressively create an implicit temporal expectation of S2 onset, reflected by the time course of the Contingent Negative Variation response, which always peaked in correspondence to the point of S2 maximum expectation and afterwards inverted in polarity towards the baseline. Brain source analysis of S1- and ISI-related ERP activity revealed activation of sensorial cortical areas and the supplementary motor area (SMA, respectively. In particular, since the SMA time course synchronised with standard ISI, we suggest that this area is the major cortical generator of the temporal CNV reflecting an automatic, action-independent mechanism underlying temporal expectancy.

Discovery of spatio-temporal patterns from location-based social networks

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Béjar, J.; Álvarez, S.; García, D.; Gómez, I.; Oliva, L.; Tejeda, A.; Vázquez-Salceda, J.

2016-03-01

Location-based social networks (LBSNs) such as Twitter or Instagram are a good source for user spatio-temporal behaviour. These networks collect data from users in such a way that they can be seen as a set of collective and distributed sensors of a geographical area. A low rate sampling of user's location information can be obtained during large intervals of time that can be used to discover complex patterns, including mobility profiles, points of interest or unusual events. These patterns can be used as the elements of a knowledge base for different applications in different domains such as mobility route planning, touristic recommendation systems or city planning. The aim of this paper is twofold, first to analyse the frequent spatio-temporal patterns that users share when living and visiting a city. This behaviour is studied by means of frequent itemsets algorithms in order to establish some associations among visits that can be interpreted as interesting routes or spatio-temporal connections. Second, to analyse how the spatio-temporal behaviour of a large number of users can be segmented in different profiles. These behavioural profiles are obtained by means of clustering algorithms that show the different patterns of behaviour of visitors and citizens. The data analysed were obtained from the public data feeds of Twitter and Instagram within an area surrounding the cities of Barcelona and Milan for a period of several months. The analysis of these data shows that these kinds of algorithms can be successfully applied to data from any city (or general area) to discover useful patterns that can be interpreted on terms of singular places and areas and their temporal relationships.

Temporal lobe structures and facial emotion recognition in schizophrenia patients and nonpsychotic relatives.

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Goghari, Vina M; Macdonald, Angus W; Sponheim, Scott R

2011-11-01

Temporal lobe abnormalities and emotion recognition deficits are prominent features of schizophrenia and appear related to the diathesis of the disorder. This study investigated whether temporal lobe structural abnormalities were associated with facial emotion recognition deficits in schizophrenia and related to genetic liability for the disorder. Twenty-seven schizophrenia patients, 23 biological family members, and 36 controls participated. Several temporal lobe regions (fusiform, superior temporal, middle temporal, amygdala, and hippocampus) previously associated with face recognition in normative samples and found to be abnormal in schizophrenia were evaluated using volumetric analyses. Participants completed a facial emotion recognition task and an age recognition control task under time-limited and self-paced conditions. Temporal lobe volumes were tested for associations with task performance. Group status explained 23% of the variance in temporal lobe volume. Left fusiform gray matter volume was decreased by 11% in patients and 7% in relatives compared with controls. Schizophrenia patients additionally exhibited smaller hippocampal and middle temporal volumes. Patients were unable to improve facial emotion recognition performance with unlimited time to make a judgment but were able to improve age recognition performance. Patients additionally showed a relationship between reduced temporal lobe gray matter and poor facial emotion recognition. For the middle temporal lobe region, the relationship between greater volume and better task performance was specific to facial emotion recognition and not age recognition. Because schizophrenia patients exhibited a specific deficit in emotion recognition not attributable to a generalized impairment in face perception, impaired emotion recognition may serve as a target for interventions.

Relative Binding Free Energy Calculations in Drug Discovery: Recent Advances and Practical Considerations.

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Cournia, Zoe; Allen, Bryce; Sherman, Woody

2017-12-26

Accurate in silico prediction of protein-ligand binding affinities has been a primary objective of structure-based drug design for decades due to the putative value it would bring to the drug discovery process. However, computational methods have historically failed to deliver value in real-world drug discovery applications due to a variety of scientific, technical, and practical challenges. Recently, a family of approaches commonly referred to as relative binding free energy (RBFE) calculations, which rely on physics-based molecular simulations and statistical mechanics, have shown promise in reliably generating accurate predictions in the context of drug discovery projects. This advance arises from accumulating developments in the underlying scientific methods (decades of research on force fields and sampling algorithms) coupled with vast increases in computational resources (graphics processing units and cloud infrastructures). Mounting evidence from retrospective validation studies, blind challenge predictions, and prospective applications suggests that RBFE simulations can now predict the affinity differences for congeneric ligands with sufficient accuracy and throughput to deliver considerable value in hit-to-lead and lead optimization efforts. Here, we present an overview of current RBFE implementations, highlighting recent advances and remaining challenges, along with examples that emphasize practical considerations for obtaining reliable RBFE results. We focus specifically on relative binding free energies because the calculations are less computationally intensive than absolute binding free energy (ABFE) calculations and map directly onto the hit-to-lead and lead optimization processes, where the prediction of relative binding energies between a reference molecule and new ideas (virtual molecules) can be used to prioritize molecules for synthesis. We describe the critical aspects of running RBFE calculations, from both theoretical and applied perspectives

Audiovisual Temporal Perception in Aging: The Role of Multisensory Integration and Age-Related Sensory Loss.

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Brooks, Cassandra J; Chan, Yu Man; Anderson, Andrew J; McKendrick, Allison M

2018-01-01

Within each sensory modality, age-related deficits in temporal perception contribute to the difficulties older adults experience when performing everyday tasks. Since perceptual experience is inherently multisensory, older adults also face the added challenge of appropriately integrating or segregating the auditory and visual cues present in our dynamic environment into coherent representations of distinct objects. As such, many studies have investigated how older adults perform when integrating temporal information across audition and vision. This review covers both direct judgments about temporal information (the sound-induced flash illusion, temporal order, perceived synchrony, and temporal rate discrimination) and judgments regarding stimuli containing temporal information (the audiovisual bounce effect and speech perception). Although an age-related increase in integration has been demonstrated on a variety of tasks, research specifically investigating the ability of older adults to integrate temporal auditory and visual cues has produced disparate results. In this short review, we explore what factors could underlie these divergent findings. We conclude that both task-specific differences and age-related sensory loss play a role in the reported disparity in age-related effects on the integration of auditory and visual temporal information.

Audiovisual Temporal Perception in Aging: The Role of Multisensory Integration and Age-Related Sensory Loss

Science.gov (United States)

Brooks, Cassandra J.; Chan, Yu Man; Anderson, Andrew J.; McKendrick, Allison M.

2018-01-01

Within each sensory modality, age-related deficits in temporal perception contribute to the difficulties older adults experience when performing everyday tasks. Since perceptual experience is inherently multisensory, older adults also face the added challenge of appropriately integrating or segregating the auditory and visual cues present in our dynamic environment into coherent representations of distinct objects. As such, many studies have investigated how older adults perform when integrating temporal information across audition and vision. This review covers both direct judgments about temporal information (the sound-induced flash illusion, temporal order, perceived synchrony, and temporal rate discrimination) and judgments regarding stimuli containing temporal information (the audiovisual bounce effect and speech perception). Although an age-related increase in integration has been demonstrated on a variety of tasks, research specifically investigating the ability of older adults to integrate temporal auditory and visual cues has produced disparate results. In this short review, we explore what factors could underlie these divergent findings. We conclude that both task-specific differences and age-related sensory loss play a role in the reported disparity in age-related effects on the integration of auditory and visual temporal information. PMID:29867415

The Relative Importance of Spatial Versus Temporal Structure in the Perception of Biological Motion: An Event-Related Potential Study

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Hirai, Masahiro; Hiraki, Kazuo

2006-01-01

We investigated how the spatiotemporal structure of animations of biological motion (BM) affects brain activity. We measured event-related potentials (ERPs) during the perception of BM under four conditions: normal spatial and temporal structure; scrambled spatial and normal temporal structure; normal spatial and scrambled temporal structure; and…

Temporal, geomagnetic and related attributes of kimberlite magmatism at Ekati, Northwest Territories, Canada

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Lockhart, Grant; Grütter, Herman; Carlson, Jon

2004-09-01

This paper outlines the development of a multi-disciplinary strategy to focus exploration for economic kimberlites on the Ekati property. High-resolution aeromagnetic data provide an over-arching spatial and magnetostratigraphic framework for exploration and kimberlite discovery at Ekati, and hence also for this investigation. The temporal, geomagnetic, spatial and related attributes of kimberlites with variable diamond content have been constrained by judiciously augmenting the information gathered during routine exploration with detailed, laboratory-based or field-based investigations. The natural remanent magnetisation of 36 Ekati kimberlites has been correlated with their age as determined by isotopic dating techniques, and placed in the context of a well-constrained geomagnetic polarity timescale. Kimberlite magmatism occurred over the period 75 to 45 Ma, in at least five temporally discrete intrusive episodes. Based on current evidence, the older kimberlites (75 to 59 Ma) have low diamond contents and are distributed throughout the property. Younger kimberlites (56 to 45 Ma) have moderate to high diamond contents and occur in three distinct intrusive corridors with NNE to NE orientations. Economic kimberlite pipes erupted at 55.4±0.4 Ma along the A154-Lynx intrusive corridor, which is 7 km wide and oriented at 015°, and at 53.2±0.3 Ma along the Panda intrusive corridor, which is 1 km wide and oriented at 038°. The intrusion ages straddle a paleopole reversal at Chron C24n, consistent with the observation that the older economic kimberlites present as aeromagnetic "low" anomalies while the younger economic pipes are characterised as aeromagnetic "highs". The aeromagnetic responses for these kimberlites are generally muted because they contain volcaniclastic rock types with low magnetic susceptibility. Kimberlites throughout the Ekati property carry a primary natural magnetic remanence (NRM) vector in Ti-bearing groundmass magnetite, and it dominates over

ASPECTUAL INFLUENCE ON TEMPORAL RELATIONS: A CASE STUDY OF THE EXPERIENTIAL GUO IN MANDARINE

Directory of Open Access Journals (Sweden)

Jiun-Shiung Wu

2009-12-01

Full Text Available This paper examines how the temporal relation between a clause containing the experiential guo and an adjacent clause is determined. Mandarin is a language not morphologically marked for tenses (e.g., Lin 2006, and therefore, tenses cannot help in determining temporal relations in Mandarin. However, Mandarin has a rich aspectual system. This paper argues that the experiential guo indirectly influences temporal relations via rhetorical relations by either specifying a default rhetorical relation, or by constraining the circumstances under which a certain rhetorical relation can connect a clause with guo to an adjacent clause. This paper also argues that the default rhetorical relation and the constraints are determined by the aspectual properties of the experiential marker. Other information, such as discourse connectors, lexical information, etc., can override the default rhetorical relation indicated by guo and specifies a rhetorical relation. Therefore, this paper concludes that in Mandarin aspect markers can indirectly affect temporal relations by means of rhetorical relations, a result consistent with Wu’s (2005b paper on the perfective marker le in Mandarin, and Wu’s (2007b, 2004 work on the progressive marker zai and the durative marker zhe.

Correlation between memory, proton magnetic resonance spectroscopy, and interictal epileptiform discharges in temporal lobe epilepsy related to mesial temporal sclerosis.

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Mantoan, Marcele Araújo Silva; Caboclo, Luís Otávio Sales Ferreira; de Figueiredo Ferreira Guilhoto, Laura Maria; Lin, Katia; da Silva Noffs, Maria Helena; de Souza Silva Tudesco, Ivanda; Belzunces, Erich; Carrete, Henrique; Bussoletti, Renato Tavares; Centeno, Ricardo Silva; Sakamoto, Américo Ceiki; Yacubian, Elza Márcia Targas

2009-11-01

The aim of the study described here was to examine the relationship between memory function, proton magnetic resonance spectroscopy ((1)H-MRS) abnormalities, and interictal epileptiform discharge (IED) lateralization in patients with temporal lobe epilepsy (TLE) related to unilateral mesial temporal sclerosis. We assessed performance on tests of memory function and intelligence quotient (IQ) in 29 right-handed outpatients and 24 controls. IEDs were assessed on 30-minute-awake and 30-minute-sleep EEG samples. Patients had (1)H-MRS at 1.5 T. There was a negative correlation between IQ (P=0.031) and Rey Auditory Verbal Learning Test results (P=0.022) and epilepsy duration; between(1)H-MRS findings and epilepsy duration (P=0.027); and between N-acetylaspartate (NAA) levels and IEDs (P=0.006) in contralateral mesial temporal structures in the left MTS group. (1)H-MRS findings, IEDs, and verbal function were correlated. These findings suggest that IEDs and NAA/(Cho+Cr) ratios reflecting neural metabolism are closely related to verbal memory function in mesial temporal sclerosis. Higher interictal activity on the EEG was associated with a decline in total NAA in contralateral mesial temporal structures.

22 CFR 35.21 - Discovery.

Science.gov (United States)

2010-04-01

... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Discovery. 35.21 Section 35.21 Foreign Relations DEPARTMENT OF STATE CLAIMS AND STOLEN PROPERTY PROGRAM FRAUD CIVIL REMEDIES § 35.21 Discovery. (a) The following types of discovery are authorized: (1) Requests for production of documents for...

Embodiment, Virtual Space, Temporality and Interpersonal Relations in Online Writing

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Adams, Catherine; van Manen, Max

2006-01-01

In this paper we discuss how online seminar participants experience dimensions of embodiment, virtual space, interpersonal relations, and temporality; and how interacting through reading-writing, by means of online technologies, creates conditions, situations, and actions of pedagogical influence and relational affectivities. We investigate what…

22 CFR 224.21 - Discovery.

Science.gov (United States)

2010-04-01

... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Discovery. 224.21 Section 224.21 Foreign....21 Discovery. (a) The following types of discovery are authorized: (1) Requests for production of... parties, discovery is available only as ordered by the ALJ. The ALJ shall regulate the timing of discovery...

IgG4-Related Disease of Bilateral Temporal Bones.

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Li, Lilun; Ward, Bryan; Cocks, Margaret; Kheradmand, Amir; Francis, Howard W

2017-03-01

IgG4-related disease (IgG4-RD) is an idiopathic inflammatory condition that causes pseudotumor formation in single or multiple organs, including those of the head and neck. Temporal bone involvement is rare, with only 3 cases of unilateral temporal bone IgG4-RD described in the literature. We report the first known case of IgG4-RD of bilateral temporal bones and describe its clinical presentation, diagnosis, and treatment. The patient was a 52-year-old man with latent tuberculosis (TB) who presented with a 10-year history of bilateral profound hearing loss and vestibular dysfunction. Computed tomography and magnetic resonance imaging demonstrated bilateral labyrinthine destruction with invasion of the posterior fossa. Immunoglobulin level testing showed elevated total serum IgG levels with normal IgG4 levels. Bilateral mastoidectomies were performed, with biopsy samples demonstrating IgG4 staining with IgG4-positive plasma cells up to 40/HPF (high power field) on the right and 20/HPF on the left, consistent with bilateral IgG4-RD. IgG4-RD of bilateral temporal bones presents with chronic and progressive bilateral hearing loss and vestibular dysfunction. Clinical presentation and radiologic findings are nonspecific, and definitive diagnosis must be made with histopathology and immunostaining. Corticosteroids are therapeutic, but surgical resection may be necessary for temporal bone IgG4-RD to improve long-term remission.

Normalization of relative and incomplete temporal expressions in clinical narratives.

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Sun, Weiyi; Rumshisky, Anna; Uzuner, Ozlem

2015-09-01

To improve the normalization of relative and incomplete temporal expressions (RI-TIMEXes) in clinical narratives. We analyzed the RI-TIMEXes in temporally annotated corpora and propose two hypotheses regarding the normalization of RI-TIMEXes in the clinical narrative domain: the anchor point hypothesis and the anchor relation hypothesis. We annotated the RI-TIMEXes in three corpora to study the characteristics of RI-TMEXes in different domains. This informed the design of our RI-TIMEX normalization system for the clinical domain, which consists of an anchor point classifier, an anchor relation classifier, and a rule-based RI-TIMEX text span parser. We experimented with different feature sets and performed an error analysis for each system component. The annotation confirmed the hypotheses that we can simplify the RI-TIMEXes normalization task using two multi-label classifiers. Our system achieves anchor point classification, anchor relation classification, and rule-based parsing accuracy of 74.68%, 87.71%, and 57.2% (82.09% under relaxed matching criteria), respectively, on the held-out test set of the 2012 i2b2 temporal relation challenge. Experiments with feature sets reveal some interesting findings, such as: the verbal tense feature does not inform the anchor relation classification in clinical narratives as much as the tokens near the RI-TIMEX. Error analysis showed that underrepresented anchor point and anchor relation classes are difficult to detect. We formulate the RI-TIMEX normalization problem as a pair of multi-label classification problems. Considering only RI-TIMEX extraction and normalization, the system achieves statistically significant improvement over the RI-TIMEX results of the best systems in the 2012 i2b2 challenge. © 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.

15 CFR 719.10 - Discovery.

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2010-01-01

... 15 Commerce and Foreign Trade 2 2010-01-01 2010-01-01 false Discovery. 719.10 Section 719.10... Discovery. (a) General. The parties are encouraged to engage in voluntary discovery regarding any matter... the Federal Rules of Civil Procedure relating to discovery apply to the extent consistent with this...

22 CFR 128.6 - Discovery.

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2010-04-01

... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Discovery. 128.6 Section 128.6 Foreign... Discovery. (a) Discovery by the respondent. The respondent, through the Administrative Law Judge, may... discovery if the interests of national security or foreign policy so require, or if necessary to comply with...

22 CFR 521.21 - Discovery.

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2010-04-01

... 22 Foreign Relations 2 2010-04-01 2010-04-01 true Discovery. 521.21 Section 521.21 Foreign... Discovery. (a) The following types of discovery are authorized: (1) Requests for production of documents for... interpreted to require the creation of a document. (c) Unless mutually agreed to by the parties, discovery is...

15 CFR 766.9 - Discovery.

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2010-01-01

... 15 Commerce and Foreign Trade 2 2010-01-01 2010-01-01 false Discovery. 766.9 Section 766.9... PROCEEDINGS § 766.9 Discovery. (a) General. The parties are encouraged to engage in voluntary discovery... provisions of the Federal Rules of Civil Procedure relating to discovery apply to the extent consistent with...

Spatial-temporal data model and fractal analysis of transportation network in GIS environment

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Feng, Yongjiu; Tong, Xiaohua; Li, Yangdong

2008-10-01

How to organize transportation data characterized by multi-time, multi-scale, multi-resolution and multi-source is one of the fundamental problems of GIS-T development. A spatial-temporal data model for GIS-T is proposed based on Spatial-temporal- Object Model. Transportation network data is systemically managed using dynamic segmentation technologies. And then a spatial-temporal database is built to integrally store geographical data of multi-time for transportation. Based on the spatial-temporal database, functions of spatial analysis of GIS-T are substantively extended. Fractal module is developed to improve the analyzing in intensity, density, structure and connectivity of transportation network based on the validation and evaluation of topologic relation. Integrated fractal with GIS-T strengthens the functions of spatial analysis and enriches the approaches of data mining and knowledge discovery of transportation network. Finally, the feasibility of the model and methods are tested thorough Guangdong Geographical Information Platform for Highway Project.

Temporal discounting rates and their relation to exercise behavior in older adults.

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Tate, Linda M; Tsai, Pao-Feng; Landes, Reid D; Rettiganti, Mallikarjuna; Lefler, Leanne L

2015-12-01

As our nation's population ages, the rates of chronic illness and disability are expected to increase significantly. Despite the knowledge that exercise may prevent chronic disease and promote health among older adults, many still are inactive. Factors related to exercise behaviors have been explored in recent years. However, temporal discounting is a motivational concept that has not been explored in regard to exercise in older adults. Temporal discounting is a decision making process by which an individual chooses a smaller more immediate reward over a larger delayed reward. The aim of this study was to determine if temporal discounting rates vary between exercising and non-exercising older adults. This study used cross-sectional survey of 137 older adults living in the community. Older adults were recruited from 11 rural Arkansas churches. The Kirby delay-discounting Monetary Choice Questionnaire was used to collect discounting rates and then bivariate analysis was performed to compare temporal discounting rate between the exercisers and non-exercisers. Finally, multivariate analysis was used to compare discounting rate controlling for other covariates. The results indicated that exercising older adults display lower temporal discounting rates than non-exercising older adults. After controlling for education, exercisers still have lower temporal discounting rates than non-exercisers (phealth conditions relate to lack of exercise especially in older adults. This research suggests that if we can find appropriate incentives for discounting individuals, some type of immediate reward, then potentially we can design programs to engage and retain older adults in exercise. Copyright © 2015 Elsevier Inc. All rights reserved.

Temporal profile of body temperature in acute ischemic stroke: Relation to infarct size and outcome

NARCIS (Netherlands)

M. Geurts (Marjolein); Scheijmans, F.E.V. (Féline E.V.); T. van Seeters (Tom); G.J. Biessels; L.J. Kappelle (Jaap); B.K. Velthuis (Birgitta K.); H.B. van der Worp (Bart); C.B. Majoie (Charles); Y.B.W.E.M. Roos (Yvo); L.E.M. Duijm (Lucien); K. Keizer (Koos); A. van der Lugt (Aad); D.W.J. Dippel (Diederik); Greve, D. (Droogh-de); H.P. Bienfait (Henri); M.A.A. van Walderveen (Marianne); M.J.H. Wermer (Marieke); G.J. Lycklama à Nijeholt (Geert); J. Boiten (Jelis); A. Duyndam (Anita); V.I.H. Kwa; F.J. Meijer (F.); E.J. van Dijk (Ewoud); A.M. Kesselring (Anouk); J. Hofmeijer; J.A. Vos (Jan Albert); W.J. Schonewille (Wouter); W.J. van Rooij (W.); P.L.M. de Kort (Paul); C.C. Pleiter (C.); S.L.M. Bakker (Stef); Bot, J.; M.C. Visser (Marieke); B.K. Velthuis (Birgitta); I.C. van der Schaaf (Irene); J.W. Dankbaar (Jan); W.P. Mali (Willem); van Seeters, T.; A.D. Horsch (Alexander D.); J.M. Niesten (Joris); G.J. Biessels (Geert Jan); L.J. Kappelle (Jaap); J.S.K. Luitse; Y. van der Graaf (Yolanda)

2016-01-01

textabstractBackground: High body temperatures after ischemic stroke have been associated with larger infarct size, but the temporal profile of this relation is unknown. We assess the relation between temporal profile of body temperature and infarct size and functional outcome in patients with acute

Sad facial cues inhibit temporal attention: evidence from an event-related potential study.

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Kong, Xianxian; Chen, Xiaoqiang; Tan, Bo; Zhao, Dandan; Jin, Zhenlan; Li, Ling

2013-06-19

We examined the influence of different emotional cues (happy or sad) on temporal attention (short or long interval) using behavioral as well as event-related potential recordings during a Stroop task. Emotional stimuli cued short and long time intervals, inducing 'sad-short', 'sad-long', 'happy-short', and 'happy-long' conditions. Following the intervals, participants performed a numeric Stroop task. Behavioral results showed the temporal attention effects in the sad-long, happy-long, and happy-short conditions, in which valid cues quickened the reaction times, but not in the sad-short condition. N2 event-related potential components showed sad cues to have decreased activity for short intervals compared with long intervals, whereas happy cues did not. Taken together, these findings provide evidence for different modulation of sad and happy facial cues on temporal attention. Furthermore, sad cues inhibit temporal attention, resulting in longer reaction time and decreased neural activity in the short interval by diverting more attentional resources.

29 CFR 2200.208 - Discovery.

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2010-07-01

... 29 Labor 9 2010-07-01 2010-07-01 false Discovery. 2200.208 Section 2200.208 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH REVIEW COMMISSION RULES OF PROCEDURE Simplified Proceedings § 2200.208 Discovery. Discovery, including requests for admissions, will only be...

Bayesian spatio-temporal modelling of tobacco-related cancer mortality in Switzerland

Directory of Open Access Journals (Sweden)

Verena Jürgens

2013-05-01

Full Text Available Tobacco smoking is a main cause of disease in Switzerland; lung cancer being the most common cancer mortality in men and the second most common in women. Although disease-specific mortality is decreasing in men, it is steadily increasing in women. The four language regions in this country might play a role in this context as they are influenced in different ways by the cultural and social behaviour of neighbouring countries. Bayesian hierarchical spatio-temporal, negative binomial models were fitted on subgroup-specific death rates indirectly standardized by national references to explore age- and gender-specific spatio-temporal patterns of mortality due to lung cancer and other tobacco-related cancers in Switzerland for the time period 1969-2002. Differences influenced by linguistic region and life in rural or urban areas were also accounted for. Male lung cancer mortality was found to be rather homogeneous in space, whereas women were confirmed to be more affected in urban regions. Compared to the German-speaking part, female mortality was higher in the French-speaking part of the country, a result contradicting other reports of similar comparisons between France and Germany. The spatio-temporal patterns of mortality were similar for lung cancer and other tobacco-related cancers. The estimated mortality maps can support the planning in health care services and evaluation of a national tobacco control programme. Better understanding of spatial and temporal variation of cancer of the lung and other tobacco-related cancers may help in allocating resources for more effective screening, diagnosis and therapy. The methodology can be applied to similar studies in other settings.

The relation between prior knowledge and students' collaborative discovery learning processes.

NARCIS (Netherlands)

Gijlers, Aaltje H.; de Jong, Anthonius J.M.

2005-01-01

In this study we investigate how prior knowledge influences knowledge development during collaborative discovery learning. Fifteen dyads of students (pre-university education, 15-16 years old) worked on a discovery learning task in the physics field of kinematics. The (face-to-face) communication

Discovery of the earliest-known tetrapod stapes.

Science.gov (United States)

Clack, J A

1989-11-23

The evolution of the middle ear is central to the discussion of how the first tetrapods adapted to life on land as well as their phylogeny. Here I report the discovery of the stapes of Acanthostega gunnari, from the Upper Devonian of east Greenland. This is the earliest tetrapod stapes so far described, and it throws new light on both these aspects of early tetrapod biology. It has been assumed that the common inheritance of all early tetrapods was a light, rod-like stapes associated with a temporal notch in the otic region that was thought to have supported a tympanum, or eardrum. The stapes would have conducted vibrations from the tympanum to the otic capsule. By contrast, the stapes of Acanthostega was stout with a broad distal ramus associated with the temporal notch. I suggest that the temporal notch of Acanthostega and other early tetrapods supported a spiracular opening rather than a tympanum, and that the stapes controlled palatal and spiracular movements in ventilation.

Get Involved in Planetary Discoveries through New Worlds, New Discoveries

Science.gov (United States)

Shupla, Christine; Shipp, S. S.; Halligan, E.; Dalton, H.; Boonstra, D.; Buxner, S.; SMD Planetary Forum, NASA

2013-01-01

"New Worlds, New Discoveries" is a synthesis of NASA’s 50-year exploration history which provides an integrated picture of our new understanding of our solar system. As NASA spacecraft head to and arrive at key locations in our solar system, "New Worlds, New Discoveries" provides an integrated picture of our new understanding of the solar system to educators and the general public! The site combines the amazing discoveries of past NASA planetary missions with the most recent findings of ongoing missions, and connects them to the related planetary science topics. "New Worlds, New Discoveries," which includes the "Year of the Solar System" and the ongoing celebration of the "50 Years of Exploration," includes 20 topics that share thematic solar system educational resources and activities, tied to the national science standards. This online site and ongoing event offers numerous opportunities for the science community - including researchers and education and public outreach professionals - to raise awareness, build excitement, and make connections with educators, students, and the public about planetary science. Visitors to the site will find valuable hands-on science activities, resources and educational materials, as well as the latest news, to engage audiences in planetary science topics and their related mission discoveries. The topics are tied to the big questions of planetary science: how did the Sun’s family of planets and bodies originate and how have they evolved? How did life begin and evolve on Earth, and has it evolved elsewhere in our solar system? Scientists and educators are encouraged to get involved either directly or by sharing "New Worlds, New Discoveries" and its resources with educators, by conducting presentations and events, sharing their resources and events to add to the site, and adding their own public events to the site’s event calendar! Visit to find quality resources and ideas. Connect with educators, students and the public to

Applications of Temporal Reasoning to Intensive Care Units

Directory of Open Access Journals (Sweden)

J. M. Juarez

2010-01-01

Full Text Available Intensive Care Units (ICUs are hospital departments that focus on the evolution of patients. In this scenario, the temporal dimension plays an essential role in understanding the state of the patients from their temporal information. The development of methods for the acquisition, modelling, reasoning and knowledge discovery of temporal information is, therefore, useful to exploit the large amount of temporal data recorded daily in the ICU. During the past decades, some subfields of Artificial Intelligence have been devoted to the study of temporal models and techniques to solve generic problems and towards their practical applications in the medical domain. The main goal of this paper is to present our view of some aspects of practical problems of temporal reasoning in the ICU field, and to describe our practical experience in the field in the last decade. This paper provides a non-exhaustive review of some of the efforts made in the field and our particular contributions in the development of temporal reasoning methods to partially solve some of these problems. The results are a set of software tools that help physicians to better understand the patient's temporal evolution.

Precipitation-runoff relations and water-quality characteristics at edge-of-field stations, Discovery Farms and Pioneer Farm, Wisconsin, 2003-8

Science.gov (United States)

Stuntebeck, Todd D.; Komiskey, Matthew J.; Peppler, Marie C.; Owens, David W.; Frame, Dennis R.

2011-01-01

A cooperative study between the U.S. Geological Survey, the University of Wisconsin (UW)-Madison Discovery Farms program (Discovery Farms), and the UW-Platteville Pioneer Farm program (Pioneer Farm) was developed to identify typical ranges and magnitudes, temporal distributions, and principal factors affecting concentrations and yields of sediment, nutrients, and other selected constituents in runoff from agricultural fields. Hydrologic and water-quality data were collected year-round at 23 edge-of-field monitoring stations on 5 privately owned Discovery Farms and on Pioneer Farm during water years 2003-8. The studied farms represented landscapes, soils, and farming systems typical of livestock farms throughout southern Wisconsin. Each farm employed a variety of soil, nutrient, and water-conservation practices to help minimize sediment and nutrient losses from fields and to improve crop productivity. This report summarizes the precipitation-runoff relations and water-quality characteristics measured in edge-of-field runoff for 26 "farm years" (aggregate years of averaged station data from all 6 farms for varying monitoring periods). A relatively wide range of constituents typically found in agricultural runoff were measured: suspended sediment, phosphorus (total, particulate, dissolved reactive, and total dissolved), and nitrogen (total, nitrate plus nitrite, organic, ammonium, total Kjeldahl and total Kjeldahl-dissolved), chloride, total solids, total suspended solids, total volatile suspended solids, and total dissolved solids. Mean annual precipitation was 32.8 inches for the study period, about 3 percent less than the 30-year mean. Overall mean annual runoff was 2.55 inches per year (about 8 percent of precipitation) and the distribution was nearly equal between periods of frozen ground (54 percent) and unfrozen ground (46 percent). Mean monthly runoff was highest during two periods: February to March and May to June. Ninety percent of annual runoff occurred

Mediator of moderators: temporal stability of intention and the intention-behavior relation.

Science.gov (United States)

Sheeran, Paschal; Abraham, Charles

2003-02-01

Intention certainty, past behavior, self-schema, anticipated regret, and attitudinal versus normative control all have been found to moderate intention-behavior relations. It is argued that moderation occurs because these variables produce "strong" intentions. Stability of intention over time is a key index of intention strength. Consequently, it was hypothesized that temporal stability of intention would mediate moderation by these other moderators. Participants (N = 185) completed questionnaire measures of theory of planned behavior constructs and moderator variables at two time points and subsequently reported their exercise behavior. Findings showed that all of the moderators, including temporal stability, were associated with significant improvements in consistency between intention and behavior. Temporal stability also mediated the effects of the other moderators, supporting the study hypothesis. Copyright 2003 Society for Personality and Social Psychology, Inc.

Visual Temporal Acuity Is Related to Auditory Speech Perception Abilities in Cochlear Implant Users.

Science.gov (United States)

Jahn, Kelly N; Stevenson, Ryan A; Wallace, Mark T

Despite significant improvements in speech perception abilities following cochlear implantation, many prelingually deafened cochlear implant (CI) recipients continue to rely heavily on visual information to develop speech and language. Increased reliance on visual cues for understanding spoken language could lead to the development of unique audiovisual integration and visual-only processing abilities in these individuals. Brain imaging studies have demonstrated that good CI performers, as indexed by auditory-only speech perception abilities, have different patterns of visual cortex activation in response to visual and auditory stimuli as compared with poor CI performers. However, no studies have examined whether speech perception performance is related to any type of visual processing abilities following cochlear implantation. The purpose of the present study was to provide a preliminary examination of the relationship between clinical, auditory-only speech perception tests, and visual temporal acuity in prelingually deafened adult CI users. It was hypothesized that prelingually deafened CI users, who exhibit better (i.e., more acute) visual temporal processing abilities would demonstrate better auditory-only speech perception performance than those with poorer visual temporal acuity. Ten prelingually deafened adult CI users were recruited for this study. Participants completed a visual temporal order judgment task to quantify visual temporal acuity. To assess auditory-only speech perception abilities, participants completed the consonant-nucleus-consonant word recognition test and the AzBio sentence recognition test. Results were analyzed using two-tailed partial Pearson correlations, Spearman's rho correlations, and independent samples t tests. Visual temporal acuity was significantly correlated with auditory-only word and sentence recognition abilities. In addition, proficient CI users, as assessed via auditory-only speech perception performance, demonstrated

Understanding Basic Temporal Relations in Primary School Pupils with Hearing Impairments.

Science.gov (United States)

Dulcić, Adinda; Bakota, Koraljka; Saler, Zrinka

2015-09-01

Time can be observed as a subjective, as well as an objective phenomenon which is a component of our life, and due to its communicational needs, it is standardized by temporal signs and symbols. The aim of this study was to determine the understanding of basic temporal relations of pupils with hearing impairments. We assumed that the knowledge of basic time relations is a precondition for the acquisition of knowledge that is connected with the understanding of the syllabus in regular school programs. Three groups of pupils have been examined: pupils with hearing impairments who attend the primary school of SUVAG Polyclinic under special condition, integrated hearing impaired pupils with minor additional difficulties who attend regular primary schools in Zagreb with a prolonged expert procedure and pupils of the control group. The subjects have been examined with a measuring instrument constructed by the expert team of the Polyclinic Suvag. Twenty nine subjects have been questioned, chronologically aged between 10 and 12.

Semantic and episodic memory in children with temporal lobe epilepsy: do they relate to literacy skills?

Science.gov (United States)

Lah, Suncica; Smith, Mary Lou

2014-01-01

Children with temporal lobe epilepsy are at risk for deficits in new learning (episodic memory) and literacy skills. Semantic memory deficits and double dissociations between episodic and semantic memory have recently been found in this patient population. In the current study we investigate whether impairments of these 2 distinct memory systems relate to literacy skills. 57 children with unilateral temporal lobe epilepsy completed tests of verbal memory (episodic and semantic) and literacy skills (reading and spelling accuracy, and reading comprehension). For the entire group, semantic memory explained over 30% of variance in each of the literacy domains. Episodic memory explained a significant, but rather small proportion (memory impairments (intact semantic/impaired episodic, intact episodic/impaired semantic) were compared, significant reductions in literacy skills were evident only in children with semantic memory impairments, but not in children with episodic memory impairments relative to the norms and to children with temporal lobe epilepsy who had intact memory. Our study provides the first evidence for differential relations between episodic and semantic memory impairments and literacy skills in children with temporal lobe epilepsy. As such, it highlights the urgent need to consider semantic memory deficits in management of children with temporal lobe epilepsy and undertake further research into the nature of reading difficulties of children with semantic memory impairments.

Identifying significant temporal variation in time course microarray data without replicates

Directory of Open Access Journals (Sweden)

Porter Weston

2009-03-01

Full Text Available Abstract Background An important component of time course microarray studies is the identification of genes that demonstrate significant time-dependent variation in their expression levels. Until recently, available methods for performing such significance tests required replicates of individual time points. This paper describes a replicate-free method that was developed as part of a study of the estrous cycle in the rat mammary gland in which no replicate data was collected. Results A temporal test statistic is proposed that is based on the degree to which data are smoothed when fit by a spline function. An algorithm is presented that uses this test statistic together with a false discovery rate method to identify genes whose expression profiles exhibit significant temporal variation. The algorithm is tested on simulated data, and is compared with another recently published replicate-free method. The simulated data consists both of genes with known temporal dependencies, and genes from a null distribution. The proposed algorithm identifies a larger percentage of the time-dependent genes for a given false discovery rate. Use of the algorithm in a study of the estrous cycle in the rat mammary gland resulted in the identification of genes exhibiting distinct circadian variation. These results were confirmed in follow-up laboratory experiments. Conclusion The proposed algorithm provides a new approach for identifying expression profiles with significant temporal variation without relying on replicates. When compared with a recently published algorithm on simulated data, the proposed algorithm appears to identify a larger percentage of time-dependent genes for a given false discovery rate. The development of the algorithm was instrumental in revealing the presence of circadian variation in the virgin rat mammary gland during the estrous cycle.

Dissociating the Representation of Action- and Sound-Related Concepts in Middle Temporal Cortex

Science.gov (United States)

Kiefer, Markus; Trumpp, Natalie; Herrnberger, Barbel; Sim, Eun-Jin; Hoenig, Klaus; Pulvermuller, Friedemann

2012-01-01

Modality-specific models of conceptual memory propose close links between concepts and the sensory-motor systems. Neuroimaging studies found, in different subject groups, that action-related and sound-related concepts activated different parts of posterior middle temporal gyrus (pMTG), suggesting a modality-specific representation of conceptual…

PKDE4J: Entity and relation extraction for public knowledge discovery.

Science.gov (United States)

Song, Min; Kim, Won Chul; Lee, Dahee; Heo, Go Eun; Kang, Keun Young

2015-10-01

Due to an enormous number of scientific publications that cannot be handled manually, there is a rising interest in text-mining techniques for automated information extraction, especially in the biomedical field. Such techniques provide effective means of information search, knowledge discovery, and hypothesis generation. Most previous studies have primarily focused on the design and performance improvement of either named entity recognition or relation extraction. In this paper, we present PKDE4J, a comprehensive text-mining system that integrates dictionary-based entity extraction and rule-based relation extraction in a highly flexible and extensible framework. Starting with the Stanford CoreNLP, we developed the system to cope with multiple types of entities and relations. The system also has fairly good performance in terms of accuracy as well as the ability to configure text-processing components. We demonstrate its competitive performance by evaluating it on many corpora and found that it surpasses existing systems with average F-measures of 85% for entity extraction and 81% for relation extraction. Copyright © 2015 Elsevier Inc. All rights reserved.

Temporal evolution of event-related desynchronization in acute stroke: A pilot study

NARCIS (Netherlands)

Tangwiriyasakul, Chayanin; Verhagen, Rens; Rutten, Wim; van Putten, Michel Johannes Antonius Maria

2014-01-01

Objective Assessment of event-related desynchronization (ERD) may assist in predicting recovery from stroke and rehabilitation, for instance in BCI applications. Here, we explore the temporal evolution of ERD during stroke recovery. Methods Ten stroke patients and eleven healthy controls were

Facilitating NCAR Data Discovery by Connecting Related Resources

Science.gov (United States)

Rosati, A.

2012-12-01

Linking datasets, creators, and users by employing the proper standards helps to increase the impact of funded research. In order for users to find a dataset, it must first be named. Data citations play the important role of giving datasets a persistent presence by assigning a formal "name" and location. This project focuses on the next step of the "name-find-use" sequence: enhancing discoverability of NCAR data by connecting related resources on the web. By examining metadata schemas that document datasets, I examined how Semantic Web approaches can help to ensure the widest possible range of data users. The focus was to move from search engine optimization (SEO) to information connectivity. Two main markup types are very visible in the Semantic Web and applicable to scientific dataset discovery: The Open Archives Initiative-Object Reuse and Exchange (OAI-ORE - www.openarchives.org) and Microdata (HTML5 and www.schema.org). My project creates pilot aggregations of related resources using both markup types for three case studies: The North American Regional Climate Change Assessment Program (NARCCAP) dataset and related publications, the Palmer Drought Severity Index (PSDI) animation and image files from NCAR's Visualization Lab (VisLab), and the multidisciplinary data types and formats from the Advanced Cooperative Arctic Data and Information Service (ACADIS). This project documents the differences between these markups and how each creates connectedness on the web. My recommendations point toward the most efficient and effective markup schema for aggregating resources within the three case studies based on the following assessment criteria: ease of use, current state of support and adoption of technology, integration with typical web tools, available vocabularies and geoinformatic standards, interoperability with current repositories and access portals (e.g. ESG, Java), and relation to data citation tools and methods.

Discovery of temporal and disease association patterns in condition-specific hospital utilization rates.

Directory of Open Access Journals (Sweden)

Julian S Haimovich

Full Text Available Identifying temporal variation in hospitalization rates may provide insights about disease patterns and thereby inform research, policy, and clinical care. However, the majority of medical conditions have not been studied for their potential seasonal variation. The objective of this study was to apply a data-driven approach to characterize temporal variation in condition-specific hospitalizations. Using a dataset of 34 million inpatient discharges gathered from hospitals in New York State from 2008-2011, we grouped all discharges into 263 clinical conditions based on the principal discharge diagnosis using Clinical Classification Software in order to mitigate the limitation that administrative claims data reflect clinical conditions to varying specificity. After applying Seasonal-Trend Decomposition by LOESS, we estimated the periodicity of the seasonal component using spectral analysis and applied harmonic regression to calculate the amplitude and phase of the condition's seasonal utilization pattern. We also introduced four new indices of temporal variation: mean oscillation width, seasonal coefficient, trend coefficient, and linearity of the trend. Finally, K-means clustering was used to group conditions across these four indices to identify common temporal variation patterns. Of all 263 clinical conditions considered, 164 demonstrated statistically significant seasonality. Notably, we identified conditions for which seasonal variation has not been previously described such as ovarian cancer, tuberculosis, and schizophrenia. Clustering analysis yielded three distinct groups of conditions based on multiple measures of seasonal variation. Our study was limited to New York State and results may not directly apply to other regions with distinct climates and health burden. A substantial proportion of medical conditions, larger than previously described, exhibit seasonal variation in hospital utilization. Moreover, the application of clustering

Temporal shifts in reef lagoon sediment composition, Discovery Bay, Jamaica

Science.gov (United States)

Perry, Christopher T.; Taylor, Kevin G.; Machent, Philip G.

2006-03-01

Discovery Bay, north Jamaica, forms a large (1.5 km wide), deep (up to 56 m) embayment that acts as a sink for reef-derived and lagoonal carbonate sediments. Since the mid-1960s, the bay has also provided a sink for inputs of bauxite sediment that are spilled during loading at a boat terminal constructed within Discovery Bay. Bauxite has accumulated across much of the southern section of the bay with surficial sediments presently composed of up to 35 weight% non-carbonate. Cores recovered from sites on the western side of the bay provide a stratigraphic record of this history of bauxite contamination across water depths from 5 to 25 m. The bauxite-influenced upper sediment horizons are clearly visible in each core from the distinctive red-brown colouration of the sediment. These sediments are composed of approximately 10% non-carbonate (bauxite) and have Fe contents of around 2-3000 μg/g (up to 7000 μg/g). The thickness of this upper bauxite-contaminated sequence increases down transect (approximately 18 cm in the shallowest core, to around 47 cm in the deepest core), and in each core overlies a sequence of 'clean' lagoon carbonates. These typically are poorly sorted carbonate sands with variable amounts of coral rubble. Down-core data on CaCO 3 and Fe content provide a chemical record of decreasing sediment contamination with depth, with the lower 'clean' carbonates composed of only around 2% non-carbonate and coral, mollusc, Amphiroa and Halimeda in the clean lagoon sands, to assemblages dominated by Halimeda and Amphiroa within the surficial sediments. At the deeper sites, no major down-core shifts in sediment constituents occur. These sites thus record a rather complex history of changes in sediment composition and chemistry. Clear shifts in chemistry and stratigraphy occur in all the cores and reflect progressive bauxite contamination in the near-surface horizons. These inputs, however, do not appear to have directly affected carbonate production, since the

Coupling Visualization and Data Analysis for Knowledge Discovery from Multi-dimensional Scientific Data

International Nuclear Information System (INIS)

Rubel, Oliver; Ahern, Sean; Bethel, E. Wes; Biggin, Mark D.; Childs, Hank; Cormier-Michel, Estelle; DePace, Angela; Eisen, Michael B.; Fowlkes, Charless C.; Geddes, Cameron G.R.; Hagen, Hans; Hamann, Bernd; Huang, Min-Yu; Keranen, Soile V.E.; Knowles, David W.; Hendriks, Chris L. Luengo; Malik, Jitendra; Meredith, Jeremy; Messmer, Peter; Prabhat; Ushizima, Daniela; Weber, Gunther H.; Wu, Kesheng

2010-01-01

Knowledge discovery from large and complex scientific data is a challenging task. With the ability to measure and simulate more processes at increasingly finer spatial and temporal scales, the growing number of data dimensions and data objects presents tremendous challenges for effective data analysis and data exploration methods and tools. The combination and close integration of methods from scientific visualization, information visualization, automated data analysis, and other enabling technologies 'such as efficient data management' supports knowledge discovery from multi-dimensional scientific data. This paper surveys two distinct applications in developmental biology and accelerator physics, illustrating the effectiveness of the described approach.

Age-Related Differences in Motor Coordination during Simultaneous Leg Flexion and Finger Extension: Influence of Temporal Pressure

OpenAIRE

Hussein, Tarek; Yiou, Eric; Larue, Jacques

2013-01-01

Although the effect of temporal pressure on spatio-temporal aspects of motor coordination and posture is well established in young adults, there is a clear lack of data on elderly subjects. This work examined the aging-related effects of temporal pressure on movement synchronization and dynamic stability. Sixteen young and eleven elderly subjects performed series of simultaneous rapid leg flexions in an erect posture paired with ipsilateral index-finger extensions, minimizing the difference b...

Role of inferior temporal neurons in visual memory. II. Multiplying temporal waveforms related to vision and memory.

Science.gov (United States)

Eskandar, E N; Optican, L M; Richmond, B J

1992-10-01

1. In the companion paper we reported on the activity of neurons in the inferior temporal (IT) cortex during a sequential pattern matching task. In this task a sample stimulus was followed by a test stimulus that was either a match or a nonmatch. Many of the neurons encoded information about the patterns of both current and previous stimuli in the temporal modulation of their responses. 2. A simple information processing model of visual memory can be formed with just four steps: 1) encode the current stimulus; 2) recall the code of a remembered stimulus; 3) compare the two codes; 4) and decide whether they are similar or different. The analysis presented in the first paper suggested that some IT neurons were performing the comparison step of visual memory. 3. We propose that IT neurons participate in the comparison of temporal waveforms related to vision and memory by multiplying them together. This product could form the basis of a crosscorrelation-based comparison. 4. We tested our hypothesis by fitting a simple multiplicative model to data from IT neurons. The model generated waveforms in separate memory and visual channels. The waveforms arising from the two channels were then multiplied on a point by point basis to yield the output waveform. The model was fitted to the actual neuronal data by a gradient descent method to find the best fit waveforms that also had the lowest total energy. 5. The multiplicative model fit the neuronal responses quite well. The multiplicative model made consistently better predictions of the actual response waveforms than did an additive model. Furthermore, the fit was better when the actual relationship between the responses and the sample and test stimuli were preserved than when that relationship was randomized. 6. We infer from the superior fit of the multiplicative model that IT neurons are multiplying temporally modulated waveforms arising from separate visual and memory systems in the comparison step of visual memory.

Altered medial temporal activation related to local glutamate levels in subjects with prodromal signs of psychosis.

Science.gov (United States)

Valli, Isabel; Stone, James; Mechelli, Andrea; Bhattacharyya, Sagnik; Raffin, Marie; Allen, Paul; Fusar-Poli, Paolo; Lythgoe, David; O'Gorman, Ruth; Seal, Marc; McGuire, Philip

2011-01-01

Both medial temporal cortical dysfunction and perturbed glutamatergic neurotransmission are regarded as fundamental pathophysiological features of psychosis. However, although animal models of psychosis suggest that these two abnormalities are interrelated, their relationship in humans has yet to be investigated. We used a combination of functional magnetic resonance imaging and magnetic resonance spectroscopy to investigate the relationship between medial temporal activation during an episodic memory task and local glutamate levels in 22 individuals with an at-risk mental state for psychosis and 14 healthy volunteers. We observed a significant between-group difference in the coupling of medial temporal activation with local glutamate levels. In control subjects, medial temporal activation during episodic encoding was positively associated with medial temporal glutamate. However, in the clinical population, medial temporal activation was reduced, and the relationship with glutamate was absent. In individuals at high risk of psychosis, medial temporal dysfunction seemed related to a loss of the normal relationship with local glutamate levels. This study provides the first evidence that links medial temporal dysfunction with the central glutamate system in humans and is consistent with evidence that drugs that modulate glutamatergic transmission might be useful in the treatment of psychosis. Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Altered medial temporal activation related to local glutamate levels in subjects with prodromal signs of psychosis.

OpenAIRE

Valli, I; Stone, J; Mechelli, A; Bhattacharyya, S; Raffin, M; Allen, P; Fusar-Poli, P; Lythgoe, D; O'Gorman, R; Seal, M; McGuire, P

2011-01-01

In individuals at high risk of psychosis, medial temporal dysfunction seemed related to a loss of the normal relationship with local glutamate levels. This study provides the first evidence that links medial temporal dysfunction with the central glutamate system in humans and is consistent with evidence that drugs that modulate glutamatergic transmission might be useful in the treatment of psychosis.

Occurrences of yawn and swallow are temporally related.

Science.gov (United States)

Abe, Kimiko; Weisz, Sarah E M; Dunn, Rachelle L; DiGioacchino, Martina C; Nyentap, Jennifer A; Stanbouly, Seta; Theurer, Julie A; Bureau, Yves; Affoo, Rebecca H; Martin, Ruth E

2015-02-01

Yawning is a stereotyped motor behavior characterized by deep inhalation and associated dilation of the respiratory tract, pronounced jaw opening, and facial grimacing. The frequency of spontaneous yawning varies over the diurnal cycle, peaking after waking and before sleep. Yawning can also be elicited by seeing or hearing another yawn, or by thinking about yawning, a phenomenon known as "contagious yawning". Yawning is mediated by a distributed network of brainstem and supratentorial brain regions, the components of which are shared with other airway behaviors including respiration, swallowing, and mastication. Nevertheless, the possibility of behavioral coordination between yawning and other brainstem-mediated functions has not been examined. Here we show, with a double-blind methodology, a greater-than-fivefold increase in rest (saliva) swallowing rate during the 10-s period immediately following contagious yawning elicited in 14 adult humans through the viewing of videotaped yawn stimuli. Sixty-five percent of yawns were followed by a swallow within 10 s and swallows accounted for 26 % of all behaviors produced during this post-yawn period. This novel finding of a tight temporal coupling between yawning and swallowing provides preliminary evidence that yawning and swallowing are physiologically related, thus extending current models of upper airway physiology and neurophysiology. Moreover, our finding suggests the possibility that yawning plays a role in eliciting rest swallowing, a view not considered in previous theories of yawning. As such, the present demonstration of a temporal association between yawning and swallowing motivates a re-examination of the longstanding question, "Why do we yawn?".

Some matters relating to the documentary evidence of the discovery of Neptune

Science.gov (United States)

Foster, N.

2014-04-01

The discovery of the planet Neptune was regarded as one of the greatest discoveries of the nineteenth century. Its existence was first detected, not by eye or with telescope, but by the mathematical analysis of the orbit of the planet Uranus. The perturbations of Uranus were under investigation by John Couch Adams (1819-92) in Cambridge, and Urban Le Verrier (1811-77) in Paris. Both these astronomers believed that the irregularities in the motion of Uranus could only be attributed to the action of an unknown planet of the Solar System. However, the circumstances of the discovery have once again become a matter of dispute and contention by some recent historians. My aim is to review the essential facts and the interpretation placed on them and to examine the conspiracy theories that have arisen from an examination of the documentary evidence. These conspiracy theories have detracted from Adams, the true merit of his early researches and his place in the history of the discovery. There has also been speculative allegations made of the character of Adams based on selected documentary evidence, which I believe is not necessarily a true representation of the facts. In presenting a fair portrayal of Adams's researches, I have reconstructed his 1845 October solution in a way that has not been done before.

A Similarity-Based Approach for Audiovisual Document Classification Using Temporal Relation Analysis

Directory of Open Access Journals (Sweden)

Ferrane Isabelle

2011-01-01

Full Text Available Abstract We propose a novel approach for video classification that bases on the analysis of the temporal relationships between the basic events in audiovisual documents. Starting from basic segmentation results, we define a new representation method that is called Temporal Relation Matrix (TRM. Each document is then described by a set of TRMs, the analysis of which makes events of a higher level stand out. This representation has been first designed to analyze any audiovisual document in order to find events that may well characterize its content and its structure. The aim of this work is to use this representation to compute a similarity measure between two documents. Approaches for audiovisual documents classification are presented and discussed. Experimentations are done on a set of 242 video documents and the results show the efficiency of our proposals.

Volatility Discovery

DEFF Research Database (Denmark)

Dias, Gustavo Fruet; Scherrer, Cristina; Papailias, Fotis

The price discovery literature investigates how homogenous securities traded on different markets incorporate information into prices. We take this literature one step further and investigate how these markets contribute to stochastic volatility (volatility discovery). We formally show...... that the realized measures from homogenous securities share a fractional stochastic trend, which is a combination of the price and volatility discovery measures. Furthermore, we show that volatility discovery is associated with the way that market participants process information arrival (market sensitivity......). Finally, we compute volatility discovery for 30 actively traded stocks in the U.S. and report that Nyse and Arca dominate Nasdaq....

Parotid radiosensitivity changes: a temporal relation to glandular circadian rhythms

International Nuclear Information System (INIS)

El-Mofty, S.K.; Hovenga, T.L.; Russell, J.E.; Simmons, D.J.

1982-01-01

The radiosensitivity of the rat parotid gland to X-radiation increased considerably towards the end of the daily light span (0800-2000 hours) and to a lesser extent before the onset of that period. The major sensitivity peak occurred at 1600 hours and coincides with a diurnal nadir in the rates of protein and RNA synthesis. The minor peak occurred at 0400 hours and was temporally related to a daily period of maximal secretory activity. It is suggested that suboptimal repair and secretion-linked cellular perturbations might contribute to the pathogenesis of the circadian increases in radiosensitivity of parotid cells. (author)

The Role of Medial Temporal Lobe Regions in Incidental and Intentional Retrieval of Item and Relational Information in Aging.

Science.gov (United States)

Wang, Wei-Chun; Giovanello, Kelly S

2016-06-01

Considerable neuropsychological and neuroimaging work indicates that the medial temporal lobes are critical for both item and relational memory retrieval. However, there remain outstanding issues in the literature, namely the extent to which medial temporal lobe regions are differentially recruited during incidental and intentional retrieval of item and relational information, and the extent to which aging may affect these neural substrates. The current fMRI study sought to address these questions; participants incidentally encoded word pairs embedded in sentences and incidental item and relational retrieval were assessed through speeded reading of intact, rearranged, and new word-pair sentences, while intentional item and relational retrieval were assessed through old/new associative recognition of a separate set of intact, rearranged, and new word pairs. Results indicated that, in both younger and older adults, anterior hippocampus and perirhinal cortex indexed incidental and intentional item retrieval in the same manner. In contrast, posterior hippocampus supported incidental and intentional relational retrieval in both age groups and an adjacent cluster in posterior hippocampus was recruited during both forms of relational retrieval for older, but not younger, adults. Our findings suggest that while medial temporal lobe regions do not differentiate between incidental and intentional forms of retrieval, there are distinct roles for anterior and posterior medial temporal lobe regions during retrieval of item and relational information, respectively, and further indicate that posterior regions may, under certain conditions, be over-recruited in healthy aging. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Temporal and extra-temporal hypoperfusion in medial temporal lobe epilepsy evaluated by arterial-spin-labeling based MRI

International Nuclear Information System (INIS)

Shen Lianfang; Zhang Zhiqiang; Lu Guangming; Yuan Cuiping; Wang Zhengge; Wang Haoxue; Huang Wei; Wei Fangyuan; Chen Guanghui; Tan Qifu

2012-01-01

Objective: To evaluate the feasibility of the lateralization of unilateral medial temporal lobe epilepsy (mTLE) by using arterial-spin-labeling (ASL) based perfusion MR imaging and investigate the changes of perfusion in the regions related to mTLE network and the relationship between the perfusion and the clinical status. Methods: Twenty-five patients with left-sided and 23 with right-sided mTLE were enrolled, and 30 healthy volunteers were recruited. The cerebral blood flow (CBF) of related region was measured based on pulsed-ASL sequence on Siemens 3 T scanner. The CBF of the mTLE group were compared with that in the controls by using ANOVA analysis. The asymmetric indices of CBF in the medial temporal lobe were calculated as the lesion side compared with the normal side in matched region in mTLE group. Results: Compared with the volunteers, the patients with mTLE showed the decrease of CBF in the bilateral medial and lateral temporal, the frontal and parietal regions relating to the default-mode network and more serious in lesion side. The CBF values of the medial temporal lobe were negatively correlated with the epilepsy duration (r=-0.51, P<0.01). The asymmetric index of CBF as-0.01 has a 76.0% (19/25) sensitivity and a 78.3% (18/23) specificity to distinguish the lesion side. Conclusions: The decrease of CBF in the temporal and extra-temporal region by ASL-based MRI suggests the functional abnormalities in the network involved by mTLE. The ASL technique is a useful tool for lateralizing the unilateral mTLE. (authors)

Spatial and temporal relations in conditioned reinforcement and observing behavior.

Science.gov (United States)

Bowe, C A; Dinsmoor, J A

1983-03-01

In Experiment 1, depressing one perch produced stimuli indicating which of two keys, if pecked, could produce food (spatial information) and depressing the other perch produced stimuli indicating whether a variable-interval or an extinction schedule was operating (temporal information). The pigeons increased the time they spent depressing the perch that produced the temporal information but did not increase the time they spent depressing the perch that produced the spatial information. In Experiment 2, pigeons that were allowed to produce combined spatial and temporal information did not acquire the perch pressing any faster or maintain it at a higher level than pigeons allowed to produce only temporal information. Later, when perching produced only spatial information, the time spent depressing the perch eventually declined. The results are not those implied by the statement that information concerning biologically important events is reinforcing but are consistent with an interpretation in terms of the acquisition of reinforcing properties by a stimulus associated with a higher density of primary reinforcement.

Join Operations in Temporal Databases

DEFF Research Database (Denmark)

Gao, D.; Jensen, Christian Søndergaard; Snodgrass, R.T.

2005-01-01

Joins are arguably the most important relational operators. Poor implementations are tantamount to computing the Cartesian product of the input relations. In a temporal database, the problem is more acute for two reasons. First, conventional techniques are designed for the evaluation of joins...... with equality predicates rather than the inequality predicates prevalent in valid-time queries. Second, the presence of temporally varying data dramatically increases the size of a database. These factors indicate that specialized techniques are needed to efficiently evaluate temporal joins. We address...... this need for efficient join evaluation in temporal databases. Our purpose is twofold. We first survey all previously proposed temporal join operators. While many temporal join operators have been defined in previous work, this work has been done largely in isolation from competing proposals, with little...

SNPServer: a real-time SNP discovery tool.

Science.gov (United States)

Savage, David; Batley, Jacqueline; Erwin, Tim; Logan, Erica; Love, Christopher G; Lim, Geraldine A C; Mongin, Emmanuel; Barker, Gary; Spangenberg, German C; Edwards, David

2005-07-01

SNPServer is a real-time flexible tool for the discovery of SNPs (single nucleotide polymorphisms) within DNA sequence data. The program uses BLAST, to identify related sequences, and CAP3, to cluster and align these sequences. The alignments are parsed to the SNP discovery software autoSNP, a program that detects SNPs and insertion/deletion polymorphisms (indels). Alternatively, lists of related sequences or pre-assembled sequences may be entered for SNP discovery. SNPServer and autoSNP use redundancy to differentiate between candidate SNPs and sequence errors. For each candidate SNP, two measures of confidence are calculated, the redundancy of the polymorphism at a SNP locus and the co-segregation of the candidate SNP with other SNPs in the alignment. SNPServer is available at http://hornbill.cspp.latrobe.edu.au/snpdiscovery.html.

Importance of individual events in temporal networks

International Nuclear Information System (INIS)

Takaguchi, Taro; Masuda, Naoki; Sato, Nobuo; Yano, Kazuo

2012-01-01

Records of time-stamped social interactions between pairs of individuals (e.g. face-to-face conversations, e-mail exchanges and phone calls) constitute a so-called temporal network. A remarkable difference between temporal networks and conventional static networks is that time-stamped events rather than links are the unit elements generating the collective behavior of nodes. We propose an importance measure for single interaction events. By generalizing the concept of the advance of events proposed by Kossinets et al (2008 Proc. 14th ACM SIGKDD Int. Conf. on Knowledge Discovery and Data Mining p 435), we propose that an event is central when it carries new information about others to the two nodes involved in the event. We find that the proposed measure properly quantifies the importance of events in connecting nodes along time-ordered paths. Because of strong heterogeneity in the importance of events present in real data, a small fraction of highly important events is necessary and sufficient to sustain the connectivity of temporal networks. Nevertheless, in contrast to the behavior of scale-free networks against link removal, this property mainly results from bursty activity patterns and not heterogeneous degree distributions. (paper)

Discovery radiomics via evolutionary deep radiomic sequencer discovery for pathologically proven lung cancer detection.

Science.gov (United States)

Shafiee, Mohammad Javad; Chung, Audrey G; Khalvati, Farzad; Haider, Masoom A; Wong, Alexander

2017-10-01

While lung cancer is the second most diagnosed form of cancer in men and women, a sufficiently early diagnosis can be pivotal in patient survival rates. Imaging-based, or radiomics-driven, detection methods have been developed to aid diagnosticians, but largely rely on hand-crafted features that may not fully encapsulate the differences between cancerous and healthy tissue. Recently, the concept of discovery radiomics was introduced, where custom abstract features are discovered from readily available imaging data. We propose an evolutionary deep radiomic sequencer discovery approach based on evolutionary deep intelligence. Motivated by patient privacy concerns and the idea of operational artificial intelligence, the evolutionary deep radiomic sequencer discovery approach organically evolves increasingly more efficient deep radiomic sequencers that produce significantly more compact yet similarly descriptive radiomic sequences over multiple generations. As a result, this framework improves operational efficiency and enables diagnosis to be run locally at the radiologist's computer while maintaining detection accuracy. We evaluated the evolved deep radiomic sequencer (EDRS) discovered via the proposed evolutionary deep radiomic sequencer discovery framework against state-of-the-art radiomics-driven and discovery radiomics methods using clinical lung CT data with pathologically proven diagnostic data from the LIDC-IDRI dataset. The EDRS shows improved sensitivity (93.42%), specificity (82.39%), and diagnostic accuracy (88.78%) relative to previous radiomics approaches.

Cassini’s Discoveries at Saturn and the Proposed Cassini Solstice Mission

Science.gov (United States)

Pappalardo, R. T.; Spilker, L. J.; Mitchell, R. T.; Cuzzi, J.; Gombosi, T. I.; Ingersoll, A. P.; Lunine, J. I.

2009-12-01

Understanding of the Saturn system has been greatly enhanced by the Cassini-Huygens mission. Fundamental discoveries have altered our views of Saturn, Titan and the other icy satellites, the rings, and magnetosphere of the system. Key discoveries include: water-rich plumes emanating from the south pole of Enceladus; hints of possible activity on Dione and of rings around Rhea; a methane hydrological cycle on Titan complete with fluvial erosion, lakes, and seas of liquid methane and ethane; non-axisymmetric ring microstructure in all moderate optical depth rings; south polar vortices on Saturn; and a unique magnetosphere that shares characteristics with both Earth’s and Jupiter’s magnetospheres. These new discoveries are directly relevant to current Solar System science goals including: planet and satellite formation processes, formation of gas giants, the nature of organic material, the history of volatiles, habitable zones and processes for life, processes that shape planetary bodies, and evolution of exoplanets. The proposed 7-year Cassini Solstice Mission would address new questions that have arisen during the Cassini Prime and Equinox Missions, and would observe seasonal and temporal change in the Saturn system to prepare for future missions to Saturn, Titan, and Enceladus. The proposed Cassini Solstice Mission would provide new science in three ways. First, it would observe seasonally and temporally dependent processes on Saturn, Titan and other icy satellites, and within the rings and magnetosphere, in a hitherto unobserved seasonal phase from equinox to solstice. Second, it would address new questions that have arisen during the mission thus far, providing qualitatively new measurements (e.g. of Enceladus and Titan) which could not be accommodated in the earlier mission phases. Tthird, it would conduct a close-in mission phase at Saturn that would provide unique science including comparison to the Juno observations at Jupiter.

Identifying food deserts and swamps based on relative healthy food access: a spatio-temporal Bayesian approach.

Science.gov (United States)

Luan, Hui; Law, Jane; Quick, Matthew

2015-12-30

Obesity and other adverse health outcomes are influenced by individual- and neighbourhood-scale risk factors, including the food environment. At the small-area scale, past research has analysed spatial patterns of food environments for one time period, overlooking how food environments change over time. Further, past research has infrequently analysed relative healthy food access (RHFA), a measure that is more representative of food purchasing and consumption behaviours than absolute outlet density. This research applies a Bayesian hierarchical model to analyse the spatio-temporal patterns of RHFA in the Region of Waterloo, Canada, from 2011 to 2014 at the small-area level. RHFA is calculated as the proportion of healthy food outlets (healthy outlets/healthy + unhealthy outlets) within 4-km from each small-area. This model measures spatial autocorrelation of RHFA, temporal trend of RHFA for the study region, and spatio-temporal trends of RHFA for small-areas. For the study region, a significant decreasing trend in RHFA is observed (-0.024), suggesting that food swamps have become more prevalent during the study period. For small-areas, significant decreasing temporal trends in RHFA were observed for all small-areas. Specific small-areas located in south Waterloo, north Kitchener, and southeast Cambridge exhibited the steepest decreasing spatio-temporal trends and are classified as spatio-temporal food swamps. This research demonstrates a Bayesian spatio-temporal modelling approach to analyse RHFA at the small-area scale. Results suggest that food swamps are more prevalent than food deserts in the Region of Waterloo. Analysing spatio-temporal trends of RHFA improves understanding of local food environment, highlighting specific small-areas where policies should be targeted to increase RHFA and reduce risk factors of adverse health outcomes such as obesity.

Temporal dominance of emotions: Measuring dynamics of food-related emotions during consumption

NARCIS (Netherlands)

Jager, G.; Schlich, P.; Tijssen, I.O.J.M.; Yao, Y.J.; Visalli, M.; Graaf, de C.; Stieger, M.A.

2014-01-01

Mapping food-evoked emotions in addition to sensory profiling is topical. In sensory profiling, the Temporal Dominance of Sensation (TDS) method focuses on the assessment of the temporal evolution of dominant sensory attributes over time. We hypothesize that food-evoked emotions also show temporal

UTP and Temporal Logic Model Checking

Science.gov (United States)

Anderson, Hugh; Ciobanu, Gabriel; Freitas, Leo

In this paper we give an additional perspective to the formal verification of programs through temporal logic model checking, which uses Hoare and He Unifying Theories of Programming (UTP). Our perspective emphasizes the use of UTP designs, an alphabetised relational calculus expressed as a pre/post condition pair of relations, to verify state or temporal assertions about programs. The temporal model checking relation is derived from a satisfaction relation between the model and its properties. The contribution of this paper is that it shows a UTP perspective to temporal logic model checking. The approach includes the notion of efficiency found in traditional model checkers, which reduced a state explosion problem through the use of efficient data structures

Scientific Prediction and Prophetic Patenting in Drug Discovery.

Science.gov (United States)

Curry, Stephen H; Schneiderman, Anne M

2015-01-01

Pharmaceutical patenting involves writing claims based on both discoveries already made, and on prophesy of future developments in an ongoing project. This is necessitated by the very different timelines involved in the drug discovery and product development process on the one hand, and successful patenting on the other. If patents are sought too early there is a risk that patent examiners will disallow claims because of lack of enablement. If patenting is delayed, claims are at risk of being denied on the basis of existence of prior art, because the body of relevant known science will have developed significantly while the project was being pursued. This review examines the role of prophetic patenting in relation to the essential predictability of many aspects of drug discovery science, promoting the concepts of discipline-related and project-related prediction. This is especially directed towards patenting activities supporting commercialization of academia-based discoveries, where long project timelines occur, and where experience, and resources to pay for patenting, are limited. The need for improved collaborative understanding among project scientists, technology transfer professionals in, for example, universities, patent attorneys, and patent examiners is emphasized.

Discovery simulations and the assessment of intuitive knowledge

NARCIS (Netherlands)

Swaak, Janine; de Jong, Anthonius J.M.

2001-01-01

The objective of the present work is to have a closer look at the relations between the features of discovery simulations, the learning processes elicited, the knowledge that results, and the methods used to measure this acquired knowledge. It is argued that discovery simulations are ‘rich’, have a

Indeterministic Temporal Logic

Directory of Open Access Journals (Sweden)

Trzęsicki Kazimierz

2015-09-01

Full Text Available The questions od determinism, causality, and freedom have been the main philosophical problems debated since the beginning of temporal logic. The issue of the logical value of sentences about the future was stated by Aristotle in the famous tomorrow sea-battle passage. The question has inspired Łukasiewicz’s idea of many-valued logics and was a motive of A. N. Prior’s considerations about the logic of tenses. In the scheme of temporal logic there are different solutions to the problem. In the paper we consider indeterministic temporal logic based on the idea of temporal worlds and the relation of accessibility between them.

DISCOVERY 2010: Spatial and temporal variability in a dynamic polar ecosystem

Science.gov (United States)

Tarling, G. A.; Ward, P.; Atkinson, A.; Collins, M. A.; Murphy, E. J.

2012-01-01

The Scotia Sea has been a focus of biological- and physical oceanographic study since the Discovery expeditions in the early 1900s. It is a physically energetic region with some of the highest levels of productivity in the Southern Ocean. It is also a region within which there have been greater than average levels of change in upper water column temperature. We describe the results of three cruises transecting the central Scotia Sea from south to north in consecutive years and covering spring, summer and autumn periods. We also report on some community level syntheses using both current-day and historical data from this region. A wide range of parameters were measured during the field campaigns, covering the physical oceanography of the region, air-sea CO 2 fluxes, macro- and micronutrient concentrations, the composition and biomass of the nano-, micro- and mesoplankton communities, and the distribution and biomass of Antarctic krill and mesopelagic fish. Process studies examined the effect of iron-stress on the physiology of primary producers, reproduction and egestion in Antarctic krill and the transfer of stable isotopes between trophic layers, from primary consumers up to birds and seals. Community level syntheses included an examination of the biomass-spectra, food-web modelling, spatial analysis of multiple trophic layers and historical species distributions. The spatial analyses in particular identified two distinct community types: a northern warmer water community and a southern cold community, their boundary being broadly consistent with the position of the Southern Antarctic Circumpolar Current Front (SACCF). Temperature and ice cover appeared to be the dominant, over-riding factors in driving this pattern. Extensive phytoplankton blooms were a major feature of the surveys, and were persistent in areas such as South Georgia. In situ and bioassay measurements emphasised the important role of iron inputs as facilitators of these blooms. Based on seasonal

The medial temporal lobes distinguish between within-item and item-context relations during autobiographical memory retrieval.

Science.gov (United States)

Sheldon, Signy; Levine, Brian

2015-12-01

During autobiographical memory retrieval, the medial temporal lobes (MTL) relate together multiple event elements, including object (within-item relations) and context (item-context relations) information, to create a cohesive memory. There is consistent support for a functional specialization within the MTL according to these relational processes, much of which comes from recognition memory experiments. In this study, we compared brain activation patterns associated with retrieving within-item relations (i.e., associating conceptual and sensory-perceptual object features) and item-context relations (i.e., spatial relations among objects) with respect to naturalistic autobiographical retrieval. We developed a novel paradigm that cued participants to retrieve information about past autobiographical events, non-episodic within-item relations, and non-episodic item-context relations with the perceptuomotor aspects of retrieval equated across these conditions. We used multivariate analysis techniques to extract common and distinct patterns of activity among these conditions within the MTL and across the whole brain, both in terms of spatial and temporal patterns of activity. The anterior MTL (perirhinal cortex and anterior hippocampus) was preferentially recruited for generating within-item relations later in retrieval whereas the posterior MTL (posterior parahippocampal cortex and posterior hippocampus) was preferentially recruited for generating item-context relations across the retrieval phase. These findings provide novel evidence for functional specialization within the MTL with respect to naturalistic memory retrieval. © 2015 Wiley Periodicals, Inc.

Tweet for health: using an online social network to examine temporal trends in weight loss-related posts.

Science.gov (United States)

Turner-McGrievy, Gabrielle M; Beets, Michael W

2015-06-01

Few studies have used social networking sites to track temporal trends in health-related posts, particularly around weight loss. To examine the temporal relationship of Twitter messages about weight loss over 1 year (2012). Temporal trends in #weightloss mentions and #fitness, #diet, and #health tweets which also had the word "weight" in them were examined using three a priori time periods: (1) holidays: pre-winter holidays, holidays, and post-holidays; (2) Season: winter and summer; and (3) New Year's: pre-New Year's and post-New Year's. Regarding #weightloss, there were 145 (95 % CI 79, 211) more posts/day during holidays and 143 (95 % CI 76, 209) more posts/day after holidays as compared to 480 pre-holiday posts/day; 232 (95 % CI 178, 286) more posts/day during the winter versus summer (441 posts/day); there was no difference in posts around New Year's. Examining social networks for trends in health-related posts may aid in timing interventions when individuals are more likely to be discussing weight loss.

Temporal networks

Science.gov (United States)

Holme, Petter; Saramäki, Jari

2012-10-01

A great variety of systems in nature, society and technology-from the web of sexual contacts to the Internet, from the nervous system to power grids-can be modeled as graphs of vertices coupled by edges. The network structure, describing how the graph is wired, helps us understand, predict and optimize the behavior of dynamical systems. In many cases, however, the edges are not continuously active. As an example, in networks of communication via e-mail, text messages, or phone calls, edges represent sequences of instantaneous or practically instantaneous contacts. In some cases, edges are active for non-negligible periods of time: e.g., the proximity patterns of inpatients at hospitals can be represented by a graph where an edge between two individuals is on throughout the time they are at the same ward. Like network topology, the temporal structure of edge activations can affect dynamics of systems interacting through the network, from disease contagion on the network of patients to information diffusion over an e-mail network. In this review, we present the emergent field of temporal networks, and discuss methods for analyzing topological and temporal structure and models for elucidating their relation to the behavior of dynamical systems. In the light of traditional network theory, one can see this framework as moving the information of when things happen from the dynamical system on the network, to the network itself. Since fundamental properties, such as the transitivity of edges, do not necessarily hold in temporal networks, many of these methods need to be quite different from those for static networks. The study of temporal networks is very interdisciplinary in nature. Reflecting this, even the object of study has many names-temporal graphs, evolving graphs, time-varying graphs, time-aggregated graphs, time-stamped graphs, dynamic networks, dynamic graphs, dynamical graphs, and so on. This review covers different fields where temporal graphs are considered

Distinct age-related differences in temporal discounting and risk taking in adolescents and young adults

NARCIS (Netherlands)

Water, E. de; Cillessen, A.H.N.; Scheres, A.P.J.

2014-01-01

Age-related differences in temporal discounting (TD) and risk taking, and their association, were examined in adolescents and young adults (n=337) aged 12-27years. Since monetary rewards are typically used in TD and risk-taking tasks, the association between monetary reward valuation and age and

A novel biological 'twin-father' temporal paradox of General Relativity in a Gödel universe - Where reproductive biology meets theoretical physics.

Science.gov (United States)

Ashrafian, Hutan

2018-03-01

Several temporal paradoxes exist in physics. These include General Relativity's grandfather and ontological paradoxes and Special Relativity's Langevin-Einstein twin-paradox. General relativity paradoxes can exist due to a Gödel universe that follows Gödel's closed timelike curves solution to Einstein's field equations. A novel biological temporal paradox of General Relativity is proposed based on reproductive biology's phenomenon of heteropaternal fecundation. Herein, dizygotic twins from two different fathers are the result of concomitant fertilization during one menstrual cycle. In this case an Oedipus-like individual exposed to a Gödel closed timelike curve would sire a child during his maternal fertilization cycle. As a consequence of heteropaternal superfecundation, he would father his own dizygotic twin and would therefore generate a new class of autofraternal superfecundation, and by doing so creating a 'twin-father' temporal paradox. Copyright © 2017 Elsevier Ltd. All rights reserved.

Topology Discovery Using Cisco Discovery Protocol

OpenAIRE

Rodriguez, Sergio R.

2009-01-01

In this paper we address the problem of discovering network topology in proprietary networks. Namely, we investigate topology discovery in Cisco-based networks. Cisco devices run Cisco Discovery Protocol (CDP) which holds information about these devices. We first compare properties of topologies that can be obtained from networks deploying CDP versus Spanning Tree Protocol (STP) and Management Information Base (MIB) Forwarding Database (FDB). Then we describe a method of discovering topology ...

Non-verbal auditory cognition in patients with temporal epilepsy before and after anterior temporal lobectomy

Directory of Open Access Journals (Sweden)

Aurélie Bidet-Caulet

2009-11-01

Full Text Available For patients with pharmaco-resistant temporal epilepsy, unilateral anterior temporal lobectomy (ATL - i.e. the surgical resection of the hippocampus, the amygdala, the temporal pole and the most anterior part of the temporal gyri - is an efficient treatment. There is growing evidence that anterior regions of the temporal lobe are involved in the integration and short-term memorization of object-related sound properties. However, non-verbal auditory processing in patients with temporal lobe epilepsy (TLE has raised little attention. To assess non-verbal auditory cognition in patients with temporal epilepsy both before and after unilateral ATL, we developed a set of non-verbal auditory tests, including environmental sounds. We could evaluate auditory semantic identification, acoustic and object-related short-term memory, and sound extraction from a sound mixture. The performances of 26 TLE patients before and/or after ATL were compared to those of 18 healthy subjects. Patients before and after ATL were found to present with similar deficits in pitch retention, and in identification and short-term memorisation of environmental sounds, whereas not being impaired in basic acoustic processing compared to healthy subjects. It is most likely that the deficits observed before and after ATL are related to epileptic neuropathological processes. Therefore, in patients with drug-resistant TLE, ATL seems to significantly improve seizure control without producing additional auditory deficits.

Spatial and temporal relations in conditioned reinforcement and observing behavior

OpenAIRE

Bowe, Craig A.; Dinsmoor, James A.

1983-01-01

In Experiment 1, depressing one perch produced stimuli indicating which of two keys, if pecked, could produce food (spatial information) and depressing the other perch produced stimuli indicating whether a variable-interval or an extinction schedule was operating (temporal information). The pigeons increased the time they spent depressing the perch that produced the temporal information but did not increase the time they spent depressing the perch that produced the spatial information. In Exp...

Non human primate models for Alzheimer's disease-related research and drug discovery

NARCIS (Netherlands)

Van Dam, Debby; De Deyn, Peter Paul

2017-01-01

Introduction: Pathophysiological mechanisms underlying Alzheimer's disease (AD) remain insufficiently documented for the identification of accurate diagnostic markers and purposeful target discovery and development. Nonhuman primates (NHPs) have important translational value given their close

DISCOVERY OF A NEW SOFT GAMMA REPEATER: SGR J0418 + 5729

International Nuclear Information System (INIS)

Van der Horst, A. J.; Connaughton, V.; Briggs, M. S.; Kouveliotou, C.; Goegues, E.; Kaneko, Y.; Wachter, S.; Granot, J.; Ramirez-Ruiz, E.; Woods, P. M.; Aptekar, R. L.; Frederiks, D. D.; Golenetskii, S.; Barthelmy, S. D.; Cummings, J. R.; Gehrels, N.; Finger, M. H.; Gelino, C. R.; Gelino, D. M.; Hurley, K.

2010-01-01

On 2009 June 5, the Gamma-ray Burst Monitor (GBM) onboard the Fermi Gamma-ray Space Telescope triggered on two short and relatively dim bursts with spectral properties similar to soft gamma repeater (SGR) bursts. Independent localizations of the bursts by triangulation with the Konus-RF and with the Swift satellite confirmed their origin from the same, previously unknown, source. The subsequent discovery of X-ray pulsations with the Rossi X-ray Timing Explorer confirmed the magnetar nature of the new source, SGR J0418 + 5729. We describe here the Fermi/GBM observations, the discovery and the localization of this new SGR, and our infrared and Chandra X-ray observations. We also present a detailed temporal and spectral study of the two GBM bursts. SGR J0418 + 5729 is the second source discovered in the same region of the sky in the last year, the other one being SGR J0501 + 4516. Both sources lie in the direction of the galactic anti-center and presumably at the nearby distance of ∼2 kpc (assuming they reside in the Perseus arm of our Galaxy). The near-threshold GBM detection of bursts from SGR J0418 + 5729 suggests that there may be more such 'dim' SGRs throughout our Galaxy, possibly exceeding the population of 'bright' SGRs. Finally, using sample statistics, we conclude that the number of observable active magnetars in our Galaxy at any given time is ∼<10, in agreement with our earlier estimates.

Bioinformatics for discovery of microbiome variation

DEFF Research Database (Denmark)

Brejnrod, Asker Daniel

of various molecular methods to build hypotheses about the impact of a copper contaminated soil. The introduction is a broad introduction to the field of microbiome research with a focus on the technologies that enable these discoveries and how some of the broader issues have related to this thesis......Sequencing based tools have revolutionized microbiology in recent years. Highthroughput DNA sequencing have allowed high-resolution studies on microbial life in many different environments and at unprecedented low cost. These culture-independent methods have helped discovery of novel bacteria...... 1 ,“Large-scale benchmarking reveals false discoveries and count transformation sensitivity in 16S rRNA gene amplicon data analysis methods used in microbiome studies”, benchmarked the performance of a variety of popular statistical methods for discovering differentially abundant bacteria . between...

Embodiment of intersubjective time: relational dynamics as attractors in the temporal coordination of interpersonal behaviors and experiences.

Science.gov (United States)

Laroche, Julien; Berardi, Anna Maria; Brangier, Eric

2014-01-01

This paper addresses the issue of "being together," and more specifically the issue of "being together in time." We provide with an integrative framework that is inspired by phenomenology, the enactive approach and dynamical systems theories. To do so, we first define embodiment as a living and lived phenomenon that emerges from agent-world coupling. We then show that embodiment is essentially dynamical and therefore we describe experiential, behavioral and brain dynamics. Both lived temporality and the temporality of the living appear to be complex, multiscale phenomena. Next we discuss embodied dynamics in the context of interpersonal interactions, and briefly review the empirical literature on between-persons temporal coordination. Overall, we propose that being together in time emerges from the relational dynamics of embodied interactions and their flexible co-regulation.

Estimating the temporal distribution of exposure-related cancers

International Nuclear Information System (INIS)

Carter, R.L.; Sposto, R.; Preston, D.L.

1993-09-01

The temporal distribution of exposure-related cancers is relevant to the study of carcinogenic mechanisms. Statistical methods for extracting pertinent information from time-to-tumor data, however, are not well developed. Separation of incidence from 'latency' and the contamination of background cases are two problems. In this paper, we present methods for estimating both the conditional distribution given exposure-related cancers observed during the study period and the unconditional distribution. The methods adjust for confounding influences of background cases and the relationship between time to tumor and incidence. Two alternative methods are proposed. The first is based on a structured, theoretically derived model and produces direct inferences concerning the distribution of interest but often requires more-specialized software. The second relies on conventional modeling of incidence and is implemented through readily available, easily used computer software. Inferences concerning the effects of radiation dose and other covariates, however, are not always obtainable directly. We present three examples to illustrate the use of these two methods and suggest criteria for choosing between them. The first approach was used, with a log-logistic specification of the distribution of interest, to analyze times to bone sarcoma among a group of German patients injected with 224 Ra. Similarly, a log-logistic specification was used in the analysis of time to chronic myelogenous leukemias among male atomic-bomb survivors. We used the alternative approach, involving conventional modeling, to estimate the conditional distribution of exposure-related acute myelogenous leukemias among male atomic-bomb survivors, given occurrence between 1 October 1950 and 31 December 1985. All analyses were performed using Poisson regression methods for analyzing grouped survival data. (J.P.N.)

Age-Related Differences in Motor Coordination during Simultaneous Leg Flexion and Finger Extension: Influence of Temporal Pressure

Science.gov (United States)

Hussein, Tarek; Yiou, Eric; Larue, Jacques

2013-01-01

Although the effect of temporal pressure on spatio-temporal aspects of motor coordination and posture is well established in young adults, there is a clear lack of data on elderly subjects. This work examined the aging-related effects of temporal pressure on movement synchronization and dynamic stability. Sixteen young and eleven elderly subjects performed series of simultaneous rapid leg flexions in an erect posture paired with ipsilateral index-finger extensions, minimizing the difference between heel and finger movement onsets. This task was repeated ten times under two temporal conditions (self-initiated [SI] vs. reaction-time [RT]). Results showed that, first, temporal pressure modified movement synchronization; the finger extension preceded swing heel-off in RT, and inversely in SI. Synchronization error and associated standard deviation were significantly greater in elderly than in young adults in SI only, i.e. in the condition where proprioception is thought to be crucial for temporal coordination. Secondly, both groups developed a significantly shorter mediolateral (ML) anticipatory postural adjustment duration in RT (high temporal pressure) than in SI. In both groups, this shortening was compensated by an increase in the anticipatory peak of centre-of-gravity (CoG) acceleration towards the stance-leg so that ML dynamic stability at foot-off, quantified with the “extrapolated centre-of-mass”, remained unchanged across temporal conditions. This increased CoG acceleration was associated with an increased anticipatory peak of ML centre-of-pressure shift towards the swing-leg in young adults only. This suggested that the ability to accelerate the CoG with the centre-of-pressure shift was degraded in elderly, probably due to weakness in the lower limb muscles. Dynamic stability at foot-off was also degraded in elderly, with a consequent increased risk of ML imbalance and falling. The present study provides new insights into the ability of elderly adults to

Age-related differences in motor coordination during simultaneous leg flexion and finger extension: influence of temporal pressure.

Directory of Open Access Journals (Sweden)

Tarek Hussein

Full Text Available Although the effect of temporal pressure on spatio-temporal aspects of motor coordination and posture is well established in young adults, there is a clear lack of data on elderly subjects. This work examined the aging-related effects of temporal pressure on movement synchronization and dynamic stability. Sixteen young and eleven elderly subjects performed series of simultaneous rapid leg flexions in an erect posture paired with ipsilateral index-finger extensions, minimizing the difference between heel and finger movement onsets. This task was repeated ten times under two temporal conditions (self-initiated [SI] vs. reaction-time [RT]. Results showed that, first, temporal pressure modified movement synchronization; the finger extension preceded swing heel-off in RT, and inversely in SI. Synchronization error and associated standard deviation were significantly greater in elderly than in young adults in SI only, i.e. in the condition where proprioception is thought to be crucial for temporal coordination. Secondly, both groups developed a significantly shorter mediolateral (ML anticipatory postural adjustment duration in RT (high temporal pressure than in SI. In both groups, this shortening was compensated by an increase in the anticipatory peak of centre-of-gravity (CoG acceleration towards the stance-leg so that ML dynamic stability at foot-off, quantified with the "extrapolated centre-of-mass", remained unchanged across temporal conditions. This increased CoG acceleration was associated with an increased anticipatory peak of ML centre-of-pressure shift towards the swing-leg in young adults only. This suggested that the ability to accelerate the CoG with the centre-of-pressure shift was degraded in elderly, probably due to weakness in the lower limb muscles. Dynamic stability at foot-off was also degraded in elderly, with a consequent increased risk of ML imbalance and falling. The present study provides new insights into the ability of

Age-related differences in motor coordination during simultaneous leg flexion and finger extension: influence of temporal pressure.

Science.gov (United States)

Hussein, Tarek; Yiou, Eric; Larue, Jacques

2013-01-01

Although the effect of temporal pressure on spatio-temporal aspects of motor coordination and posture is well established in young adults, there is a clear lack of data on elderly subjects. This work examined the aging-related effects of temporal pressure on movement synchronization and dynamic stability. Sixteen young and eleven elderly subjects performed series of simultaneous rapid leg flexions in an erect posture paired with ipsilateral index-finger extensions, minimizing the difference between heel and finger movement onsets. This task was repeated ten times under two temporal conditions (self-initiated [SI] vs. reaction-time [RT]). Results showed that, first, temporal pressure modified movement synchronization; the finger extension preceded swing heel-off in RT, and inversely in SI. Synchronization error and associated standard deviation were significantly greater in elderly than in young adults in SI only, i.e. in the condition where proprioception is thought to be crucial for temporal coordination. Secondly, both groups developed a significantly shorter mediolateral (ML) anticipatory postural adjustment duration in RT (high temporal pressure) than in SI. In both groups, this shortening was compensated by an increase in the anticipatory peak of centre-of-gravity (CoG) acceleration towards the stance-leg so that ML dynamic stability at foot-off, quantified with the "extrapolated centre-of-mass", remained unchanged across temporal conditions. This increased CoG acceleration was associated with an increased anticipatory peak of ML centre-of-pressure shift towards the swing-leg in young adults only. This suggested that the ability to accelerate the CoG with the centre-of-pressure shift was degraded in elderly, probably due to weakness in the lower limb muscles. Dynamic stability at foot-off was also degraded in elderly, with a consequent increased risk of ML imbalance and falling. The present study provides new insights into the ability of elderly adults to deal

Abnormalities of Early “Memory-Scanning” Event-Related Potentials in Patients with Temporal Lobe Epilepsy

Directory of Open Access Journals (Sweden)

A. Grippo

1994-01-01

Full Text Available We have recorded auditory event-related potentials (ERPs evoked by the “memory-scanning” (digit-probe identification/matching paradigm that was originally described by Sternberg (1966, in 17 patients with complex partial seizures (temporal lobe epilepsy and in 17 matched healthy control subjects. The patients, who had all complained spontaneously of memory difficulties, had significantly reduced scores on psychological tests of memory with relatively intact digit span and cognition. Their performance of the memory-scanning task was characterized by a higher error rate, longer reaction times and an increased slope of the reaction time/set size relationship. The associated ERPs in both patients and controls showed there were significant effects of memory load on several major components, but only a reduced amplitude of the N170 and a prolonged latency of the N290 waves distinguished the patients. In addition, the N170 wave in the patients decreased further as memory load increased. The prolonged N290 latency in the patients appeared to reflect the slowed processing time. This study has shown that ERPs generated by a short-term memory task are abnormal in patients with temporal lobe epilepsy who have neuropsychologically documented cognitive and memory deficits. Some of the significant waveform alterations occur earlier than those reported in previous ERP studies and provide electrophysiological support for the hypothesis that abnormalities of the early stages of short-term memory processing may contribute to the memory difficulties experienced by patients with temporal lobe epilepsy.

Relative light yield and temporal response of a stilbene-doped bibenzyl organic scintillator for neutron detection

Energy Technology Data Exchange (ETDEWEB)

Brown, J. A.; Goldblum, B. L., E-mail: bethany@nuc.berkeley.edu; Brickner, N. M.; Daub, B. H.; Kaufman, G. S.; Bibber, K. van; Vujic, J. [Department of Nuclear Engineering, University of California, Berkeley, California 94720 (United States); Bernstein, L. A.; Bleuel, D. L.; Caggiano, J. A.; Hatarik, R.; Phillips, T. W.; Zaitseva, N. P. [Lawrence Livermore National Laboratory, Livermore, California 94551 (United States); Wender, S. A. [Los Alamos National Laboratory, Los Alamos, New Mexico 87545 (United States)

2014-05-21

The neutron time-of-flight (nTOF) diagnostics used to characterize implosions at the National Ignition Facility (NIF) has necessitated the development of novel scintillators that exhibit a rapid temporal response and high light yield. One such material, a bibenzyl-stilbene mixed single-crystal organic scintillator grown in a 99.5:0.5 ratio in solution, has become the standard scintillator used for nTOF diagnostics at NIF. The prompt fluorescence lifetime and relative light yield as a function of proton energy were determined to calibrate this material as a neutron detector. The temporal evolution of the intensity of the prompt fluorescent response was modeled using first-order reaction kinetics and the prompt fluorescence decay constant was determined to be 2.46 ± 0.01 (fit) ± 0.13 (systematic) ns. The relative response of the bibenzyl-stilbene mixed crystal generated by recoiling protons was measured, and results were analyzed using Birks' relation to quantify the non-radiative quenching of excitation energy in the scintillator.

Beyond discovery: A review of the critique of the discovery view of opportunities

DEFF Research Database (Denmark)

Korsgaard, Steffen T.

This paper systematically reviews and synthesises the critique since 2000 of the discovery view's interpretation of entrepreneurial opportunities. The review shows that the framing of the debate as polarised between two oppositions, the discovery view versus the creation view, is oversimplified....... The issue of whether opportunities are discovered or created is simply one of several key issues in play in the debate. These key issues include questions concerning agency, process, and the role of subjectivity, creativity and interpretation. Propositions for future research are developed from the critique......, emphasising distributed agency, non-linear processes, opportunities as formed, and the role of creativity. However, the paper also points to unresolved issues in relation to all four propositions that require further empirical and conceptual work....

14 CFR 406.143 - Discovery.

Science.gov (United States)

2010-01-01

... 14 Aeronautics and Space 4 2010-01-01 2010-01-01 false Discovery. 406.143 Section 406.143... Transportation Adjudications § 406.143 Discovery. (a) Initiation of discovery. Any party may initiate discovery... after a complaint has been filed. (b) Methods of discovery. The following methods of discovery are...

Scientific Discovery through Citizen Science via Popular Amateur Astrophotography

Science.gov (United States)

Nemiroff, Robert J.; Bonnell, Jerry T.; Allen, Alice

2015-01-01

Can popular astrophotography stimulate real astronomical discovery? Perhaps surprisingly, in some cases, the answer is yes. Several examples are given using the Astronomy Picture of the Day (APOD) site as an example venue. One reason is angular -- popular wide and deep images sometimes complement professional images which typically span a more narrow field. Another reason is temporal -- an amateur is at the right place and time to take a unique and illuminating image. Additionally, popular venues can be informational -- alerting professionals to cutting-edge amateur astrophotography about which they might not have known previously. Methods of further encouraging this unusual brand of citizen science are considered.

Higgs Discovery

DEFF Research Database (Denmark)

Sannino, Francesco

2013-01-01

has been challenged by the discovery of a not-so-heavy Higgs-like state. I will therefore review the recent discovery \\cite{Foadi:2012bb} that the standard model top-induced radiative corrections naturally reduce the intrinsic non-perturbative mass of the composite Higgs state towards the desired...... via first principle lattice simulations with encouraging results. The new findings show that the recent naive claims made about new strong dynamics at the electroweak scale being disfavoured by the discovery of a not-so-heavy composite Higgs are unwarranted. I will then introduce the more speculative......I discuss the impact of the discovery of a Higgs-like state on composite dynamics starting by critically examining the reasons in favour of either an elementary or composite nature of this state. Accepting the standard model interpretation I re-address the standard model vacuum stability within...

Scientometrics of drug discovery efforts: pain-related molecular targets

Directory of Open Access Journals (Sweden)

Kissin I

2015-07-01

Full Text Available Igor KissinDepartment of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USAAbstract: The aim of this study was to make a scientometric assessment of drug discovery efforts centered on pain-related molecular targets. The following scientometric indices were used: the popularity index, representing the share of articles (or patents on a specific topic among all articles (or patents on pain over the same 5-year period; the index of change, representing the change in the number of articles (or patents on a topic from one 5-year period to the next; the index of expectations, representing the ratio of the number of all types of articles on a topic in the top 20 journals relative to the number of articles in all (>5,000 biomedical journals covered by PubMed over a 5-year period; the total number of articles representing Phase I–III trials of investigational drugs over a 5-year period; and the trial balance index, a ratio of Phase I–II publications to Phase III publications. Articles (PubMed database and patents (US Patent and Trademark Office database on 17 topics related to pain mechanisms were assessed during six 5-year periods from 1984 to 2013. During the most recent 5-year period (2009–2013, seven of 17 topics have demonstrated high research activity (purinergic receptors, serotonin, transient receptor potential channels, cytokines, gamma aminobutyric acid, glutamate, and protein kinases. However, even with these seven topics, the index of expectations decreased or did not change compared with the 2004–2008 period. In addition, publications representing Phase I–III trials of investigational drugs (2009–2013 did not indicate great enthusiasm on the part of the pharmaceutical industry regarding drugs specifically designed for treatment of pain. A promising development related to the new tool of molecular targeting, ie, monoclonal antibodies, for pain treatment has not

Characterization and correction of the false-discovery rates in resting state connectivity using functional near-infrared spectroscopy

Science.gov (United States)

Santosa, Hendrik; Aarabi, Ardalan; Perlman, Susan B.; Huppert, Theodore J.

2017-05-01

Functional near-infrared spectroscopy (fNIRS) is a noninvasive neuroimaging technique that uses low levels of red to near-infrared light to measure changes in cerebral blood oxygenation. Spontaneous (resting state) functional connectivity (sFC) has become a critical tool for cognitive neuroscience for understanding task-independent neural networks, revealing pertinent details differentiating healthy from disordered brain function, and discovering fluctuations in the synchronization of interacting individuals during hyperscanning paradigms. Two of the main challenges to sFC-NIRS analysis are (i) the slow temporal structure of both systemic physiology and the response of blood vessels, which introduces false spurious correlations, and (ii) motion-related artifacts that result from movement of the fNIRS sensors on the participants' head and can introduce non-normal and heavy-tailed noise structures. In this work, we systematically examine the false-discovery rates of several time- and frequency-domain metrics of functional connectivity for characterizing sFC-NIRS. Specifically, we detail the modifications to the statistical models of these methods needed to avoid high levels of false-discovery related to these two sources of noise in fNIRS. We compare these analysis procedures using both simulated and experimental resting-state fNIRS data. Our proposed robust correlation method has better performance in terms of being more reliable to the noise outliers due to the motion artifacts.

A quantum causal discovery algorithm

Science.gov (United States)

Giarmatzi, Christina; Costa, Fabio

2018-03-01

Finding a causal model for a set of classical variables is now a well-established task—but what about the quantum equivalent? Even the notion of a quantum causal model is controversial. Here, we present a causal discovery algorithm for quantum systems. The input to the algorithm is a process matrix describing correlations between quantum events. Its output consists of different levels of information about the underlying causal model. Our algorithm determines whether the process is causally ordered by grouping the events into causally ordered non-signaling sets. It detects if all relevant common causes are included in the process, which we label Markovian, or alternatively if some causal relations are mediated through some external memory. For a Markovian process, it outputs a causal model, namely the causal relations and the corresponding mechanisms, represented as quantum states and channels. Our algorithm opens the route to more general quantum causal discovery methods.

The discovery of the periodic table as a case of simultaneous discovery.

Science.gov (United States)

Scerri, Eric

2015-03-13

The article examines the question of priority and simultaneous discovery in the context of the discovery of the periodic system. It is argued that rather than being anomalous, simultaneous discovery is the rule. Moreover, I argue that the discovery of the periodic system by at least six authors in over a period of 7 years represents one of the best examples of a multiple discovery. This notion is supported by a new view of the evolutionary development of science through a mechanism that is dubbed Sci-Gaia by analogy with Lovelock's Gaia hypothesis. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

Beyond Discovery

DEFF Research Database (Denmark)

Korsgaard, Steffen; Sassmannshausen, Sean Patrick

2017-01-01

In this chapter we explore four alternatives to the dominant discovery view of entrepreneurship; the development view, the construction view, the evolutionary view, and the Neo-Austrian view. We outline the main critique points of the discovery presented in these four alternatives, as well...

"Eureka, Eureka!" Discoveries in Science

Science.gov (United States)

Agarwal, Pankaj

2011-01-01

Accidental discoveries have been of significant value in the progress of science. Although accidental discoveries are more common in pharmacology and chemistry, other branches of science have also benefited from such discoveries. While most discoveries are the result of persistent research, famous accidental discoveries provide a fascinating…

30 CFR 44.24 - Discovery.

Science.gov (United States)

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Discovery. 44.24 Section 44.24 Mineral... Discovery. Parties shall be governed in their conduct of discovery by appropriate provisions of the Federal... discovery. Alternative periods of time for discovery may be prescribed by the presiding administrative law...

19 CFR 356.20 - Discovery.

Science.gov (United States)

2010-04-01

... 19 Customs Duties 3 2010-04-01 2010-04-01 false Discovery. 356.20 Section 356.20 Customs Duties... § 356.20 Discovery. (a) Voluntary discovery. All parties are encouraged to engage in voluntary discovery... sanctions proceeding. (b) Limitations on discovery. The administrative law judge shall place such limits...

Chemical Discovery

Science.gov (United States)

Brown, Herbert C.

1974-01-01

The role of discovery in the advance of the science of chemistry and the factors that are currently operating to handicap that function are considered. Examples are drawn from the author's work with boranes. The thesis that exploratory research and discovery should be encouraged is stressed. (DT)

A temporal interestingness measure for drug interaction signal detection in post-marketing surveillance.

Science.gov (United States)

Ji, Yanqing; Ying, Hao; Tran, John; Dews, Peter; Mansour, Ayman; Massanari, R Michael

2014-01-01

Drug-drug interactions (DDIs) can result in serious consequences, including death. Existing methods for identifying potential DDIs in post-marketing surveillance primarily rely on the FDA's (Food and Drug Administration) spontaneous reporting system. However, this system suffers from severe underreporting, which makes it difficult to timely collect enough valid cases for statistical analysis. In this paper, we study how to signal potential DDIs using patient electronic health data. Specifically, we focus on discovery of potential DDIs by analyzing the temporal relationships between the concurrent use of two drugs of interest and the occurrences of various symptoms using novel temporal association mining techniques we developed. A new interestingness measure called functional temporal interest was proposed to assess the degrees of temporal association between two drugs of interest and each symptom. The measure was employed to screen potential DDIs from 21,405 electronic patient cases retrieved from the Veterans Affairs Medical Center in Detroit, Michigan. The preliminary results indicate the usefulness of our method in finding potential DDIs for further analysis (e.g., epidemiology study) and investigation (e.g., case review) by drug safety professionals.

24 CFR 180.500 - Discovery.

Science.gov (United States)

2010-04-01

... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Discovery. 180.500 Section 180.500... OPPORTUNITY CONSOLIDATED HUD HEARING PROCEDURES FOR CIVIL RIGHTS MATTERS Discovery § 180.500 Discovery. (a) In general. This subpart governs discovery in aid of administrative proceedings under this part. Discovery in...

Metagenomics as a Tool for Enzyme Discovery: Hydrolytic Enzymes from Marine-Related Metagenomes.

Science.gov (United States)

Popovic, Ana; Tchigvintsev, Anatoly; Tran, Hai; Chernikova, Tatyana N; Golyshina, Olga V; Yakimov, Michail M; Golyshin, Peter N; Yakunin, Alexander F

2015-01-01

This chapter discusses metagenomics and its application for enzyme discovery, with a focus on hydrolytic enzymes from marine metagenomic libraries. With less than one percent of culturable microorganisms in the environment, metagenomics, or the collective study of community genetics, has opened up a rich pool of uncharacterized metabolic pathways, enzymes, and adaptations. This great untapped pool of genes provides the particularly exciting potential to mine for new biochemical activities or novel enzymes with activities tailored to peculiar sets of environmental conditions. Metagenomes also represent a huge reservoir of novel enzymes for applications in biocatalysis, biofuels, and bioremediation. Here we present the results of enzyme discovery for four enzyme activities, of particular industrial or environmental interest, including esterase/lipase, glycosyl hydrolase, protease and dehalogenase.

Henri Becquerel: the discovery of radioactivity

International Nuclear Information System (INIS)

Allisy, A.

1996-01-01

This paper recalls the history of the Becquerel family, the fascinating time of the discovery of radioactivity as well as some important related research published before the radium age. Henri Becquerel was the third in the line of a family of scientists which extended over more than a hundred years. Following in the footsteps of his father and grandfather gave him a thorough grounding in scientific research methods. Science at the turn of the century was very exciting, the discovery of X rays had just been announced and scientists everywhere were hoping to discover new phenomena. (author)

Right mesial temporal lobe epilepsy impairs empathy-related brain responses to dynamic fearful faces.

Science.gov (United States)

Toller, Gianina; Adhimoolam, Babu; Grunwald, Thomas; Huppertz, Hans-Jürgen; Kurthen, Martin; Rankin, Katherine P; Jokeit, Hennric

2015-03-01

Unilateral mesial temporal lobe epilepsy (MTLE) has been associated with reduced amygdala responsiveness to fearful faces. However, the effect of unilateral MTLE on empathy-related brain responses in extra-amygdalar regions has not been investigated. Using functional magnetic resonance imaging, we measured empathy-related brain responses to dynamic fearful faces in 34 patients with unilateral MTLE (18 right sided), in an epilepsy (extra-MTLE; n = 16) and in a healthy control group (n = 30). The primary finding was that right MTLE (RMTLE) was associated with decreased activity predominantly in the right amygdala and also in bilateral periaqueductal gray (PAG) but normal activity in the right anterior insula. The results of the extra-MTLE group demonstrate that these reduced amygdala and PAG responses go beyond the attenuation caused by antiepileptic and antidepressant medication. These findings clearly indicate that RMTLE affects the function of mesial temporal and midbrain structures that mediate basic interoceptive input necessary for the emotional awareness of empathic experiences of fear. Together with the decreased empathic concern found in the RMTLE group, this study provides neurobehavioral evidence that patients with RMTLE are at increased risk for reduced empathy towards others' internal states and sheds new light on the nature of social-cognitive impairments frequently accompanying MTLE.

19 CFR 207.109 - Discovery.

Science.gov (United States)

2010-04-01

... 19 Customs Duties 3 2010-04-01 2010-04-01 false Discovery. 207.109 Section 207.109 Customs Duties... and Committee Proceedings § 207.109 Discovery. (a) Discovery methods. All parties may obtain discovery under such terms and limitations as the administrative law judge may order. Discovery may be by one or...

15 CFR 25.21 - Discovery.

Science.gov (United States)

2010-01-01

... 15 Commerce and Foreign Trade 1 2010-01-01 2010-01-01 false Discovery. 25.21 Section 25.21... Discovery. (a) The following types of discovery are authorized: (1) Requests for production of documents for..., discovery is available only as ordered by the ALJ. The ALJ shall regulate the timing of discovery. (d...

The Temporality of Power and the Power of Temporality

DEFF Research Database (Denmark)

Costas, Jana; Grey, Christopher

2014-01-01

This paper extends existing understandings of power, resistance and subjectivity in professional service organizations by developing an analysis of how these relate to temporality. Drawing in particular on Hoy’s reading of the Foucauldian account of temporality, we conceive of disciplinary power...... regimes and resistance as inherently future-oriented, or, to use Ybema’s term, postalgic. In moving beyond the extant research focus on self-disciplined and/or counter-resistant professional selves, we draw attention to the imaginary future self as an employee response to disciplinary power. In contrast...

Predictors of timing of pregnancy discovery.

Science.gov (United States)

McCarthy, Molly; Upadhyay, Ushma; Biggs, M Antonia; Anthony, Renaisa; Holl, Jennifer; Roberts, Sarah Cm

2018-04-01

Earlier pregnancy discovery is important in the context of prenatal and abortion care. We evaluated characteristics associated with later pregnancy discovery among women seeking abortion care. Data come from a survey of women seeking abortion care at four family planning facilities in Utah. The participants completed a survey during the state-mandated abortion information visit they are required to complete prior to having an abortion. The outcome in this study was pregnancy discovery before versus after 6 weeks since respondents' last menstrual period (LMP). We used logistic regression to estimate the relationship between sociodemographic and health-related independent variables of interest and pregnancy discovery before versus after 6 weeks. Among the 458 women in the sample, 28% discovered their pregnancy later than 6 weeks since LMP. Most (n=366, 80%) knew the exact date of their LMP and a significant minority estimated it (n=92, 20%). Those who estimated the date of their LMP had higher odds of later pregnancy discovery than those who knew the exact date (adjusted odds ratio (aOR)=1.81[1.07-3.07]). Those who used illicit drugs weekly, daily, or almost daily had higher odds of later pregnancy discovery (aOR=6.33[2.44, 16.40]). Women who did not track their menstrual periods and those who frequently used drugs had higher odds of discovering their pregnancies later. Women who estimated the date of their LMP and who frequently used drugs may benefit from strategies to help them recognize their pregnancies earlier and link them to care when they discover their pregnancies later. Copyright © 2017 Elsevier Inc. All rights reserved.

Discovery of time-delayed gene regulatory networks based on temporal gene expression profiling

Directory of Open Access Journals (Sweden)

Guo Zheng

2006-01-01

Full Text Available Abstract Background It is one of the ultimate goals for modern biological research to fully elucidate the intricate interplays and the regulations of the molecular determinants that propel and characterize the progression of versatile life phenomena, to name a few, cell cycling, developmental biology, aging, and the progressive and recurrent pathogenesis of complex diseases. The vast amount of large-scale and genome-wide time-resolved data is becoming increasing available, which provides the golden opportunity to unravel the challenging reverse-engineering problem of time-delayed gene regulatory networks. Results In particular, this methodological paper aims to reconstruct regulatory networks from temporal gene expression data by using delayed correlations between genes, i.e., pairwise overlaps of expression levels shifted in time relative each other. We have thus developed a novel model-free computational toolbox termed TdGRN (Time-delayed Gene Regulatory Network to address the underlying regulations of genes that can span any unit(s of time intervals. This bioinformatics toolbox has provided a unified approach to uncovering time trends of gene regulations through decision analysis of the newly designed time-delayed gene expression matrix. We have applied the proposed method to yeast cell cycling and human HeLa cell cycling and have discovered most of the underlying time-delayed regulations that are supported by multiple lines of experimental evidence and that are remarkably consistent with the current knowledge on phase characteristics for the cell cyclings. Conclusion We established a usable and powerful model-free approach to dissecting high-order dynamic trends of gene-gene interactions. We have carefully validated the proposed algorithm by applying it to two publicly available cell cycling datasets. In addition to uncovering the time trends of gene regulations for cell cycling, this unified approach can also be used to study the complex

Temporally Adrift and Permanently Liminal: Relations, Dystalgia and a U.S. University as Site of Transition and Frontier

Directory of Open Access Journals (Sweden)

Frank G. Karioris

2016-04-01

Full Text Available This article seeks to explore temporal reconceptualizations and forms of nostalgia that first-year university men are experiencing and creating. It will explore the ways that time can be conceived of in relation to the present and a future that is not-yet-existent. The article takes as its starting point ethnographic fieldwork in the 21st century at a private, Catholic university in the U.S. and, in particular, men in an all-male residence hall. In focusing on this hall, it means to locate and localize the thinking in the context of the 21st century as well as within the U.S., including ne-oliberalism as a social and economic method of relating. Through the exploration of these men's envisioning of themselves as their future selves and the way they review the self that is now, this article makes a claim that they are - through both their actions, ways of relating, and the societal positioning - multiply liminal. Further, it will explore the way that through this temporal representation they are endowing themselves as permanently liminal both currently and in the future. The article situates these men amidst the university as an institution, as well as seeking to elucidate the importance of this temporal creation as a building of forms of transition and frontier.

39 CFR 963.14 - Discovery.

Science.gov (United States)

2010-07-01

... 39 Postal Service 1 2010-07-01 2010-07-01 false Discovery. 963.14 Section 963.14 Postal Service... PANDERING ADVERTISEMENTS STATUTE, 39 U.S.C. 3008 § 963.14 Discovery. Discovery is to be conducted on a... such discovery as he or she deems reasonable and necessary. Discovery may include one or more of the...

Simultaneity and Temporal Order Judgments Are Coded Differently and Change With Age: An Event-Related Potential Study

Directory of Open Access Journals (Sweden)

Aysha Basharat

2018-04-01

Full Text Available Multisensory integration is required for a number of daily living tasks where the inability to accurately identify simultaneity and temporality of multisensory events results in errors in judgment leading to poor decision-making and dangerous behavior. Previously, our lab discovered that older adults exhibited impaired timing of audiovisual events, particularly when making temporal order judgments (TOJs. Simultaneity judgments (SJs, however, were preserved across the lifespan. Here, we investigate the difference between the TOJ and SJ tasks in younger and older adults to assess neural processing differences between these two tasks and across the lifespan. Event-related potentials (ERPs were studied to determine between-task and between-age differences. Results revealed task specific differences in perceiving simultaneity and temporal order, suggesting that each task may be subserved via different neural mechanisms. Here, auditory N1 and visual P1 ERP amplitudes confirmed that unisensory processing of audiovisual stimuli did not differ between the two tasks within both younger and older groups, indicating that performance differences between tasks arise either from multisensory integration or higher-level decision-making. Compared to younger adults, older adults showed a sustained higher auditory N1 ERP amplitude response across SOAs, suggestive of broader response properties from an extended temporal binding window. Our work provides compelling evidence that different neural mechanisms subserve the SJ and TOJ tasks and that simultaneity and temporal order perception are coded differently and change with age.

Temporal dynamics of disgust and morality: an event-related potential study.

Directory of Open Access Journals (Sweden)

Qun Yang

Full Text Available Disgust is argued to be an emotion that motivates the avoidance of disease-causing entities in the physical domain and unacceptable behaviors in the social-moral domain. Empirical work from behavioral, physiological and brain imaging studies suggests moral judgments are strongly modulated by disgust feelings. Yet, it remains unclear how they are related in the time course of neural processing. Examining the temporal order of disgust emotion and morality could help to clarify the role of disgust in moral judgments. In the present research, a Go/No-Go paradigm was employed to evoke lateralized readiness potentials (LRPs to investigate the temporal order of physical disgust and moral information processing. Participants were asked to give a "yes" or "no" response regarding the physical disgust and moral wrongness of a social act. The results showed that the evaluation of moral information was processed prior to that of physical disgust information. This suggests that moral information is available earlier than physical disgust, and provides more data on the biological heterogeneity between disgust and morality in terms of the time course of neural activity. The findings implicate that physical disgust emotion may not be necessary for people to make moral judgments. They also suggest that some of our moral experience may be more fundamental (than physical disgust experience to our survival and development, as humans spend a considerable amount of time engaging in social interaction.

Integration of distributed computing into the drug discovery process.

Science.gov (United States)

von Korff, Modest; Rufener, Christian; Stritt, Manuel; Freyss, Joel; Bär, Roman; Sander, Thomas

2011-02-01

Grid computing offers an opportunity to gain massive computing power at low costs. We give a short introduction into the drug discovery process and exemplify the use of grid computing for image processing, docking and 3D pharmacophore descriptor calculations. The principle of a grid and its architecture are briefly explained. More emphasis is laid on the issues related to a company-wide grid installation and embedding the grid into the research process. The future of grid computing in drug discovery is discussed in the expert opinion section. Most needed, besides reliable algorithms to predict compound properties, is embedding the grid seamlessly into the discovery process. User friendly access to powerful algorithms without any restrictions, that is, by a limited number of licenses, has to be the goal of grid computing in drug discovery.

Relations between perceptual measures of temporal processing, auditory-evoked brainstem responses and speech intelligibility in noise

DEFF Research Database (Denmark)

Papakonstantinou, Alexandra; Strelcyk, Olaf; Dau, Torsten

2011-01-01

This study investigates behavioural and objective measures of temporal auditory processing and their relation to the ability to understand speech in noise. The experiments were carried out on a homogeneous group of seven hearing-impaired listeners with normal sensitivity at low frequencies (up to 1...... kHz) and steeply sloping hearing losses above 1 kHz. For comparison, data were also collected for five normalhearing listeners. Temporal processing was addressed at low frequencies by means of psychoacoustical frequency discrimination, binaural masked detection and amplitude modulation (AM......) detection. In addition, auditory brainstem responses (ABRs) to clicks and broadband rising chirps were recorded. Furthermore, speech reception thresholds (SRTs) were determined for Danish sentences in speechshaped noise. The main findings were: (1) SRTs were neither correlated with hearing sensitivity...

Usability of Discovery Portals

OpenAIRE

Bulens, J.D.; Vullings, L.A.E.; Houtkamp, J.M.; Vanmeulebrouk, B.

2013-01-01

As INSPIRE progresses to be implemented in the EU, many new discovery portals are built to facilitate finding spatial data. Currently the structure of the discovery portals is determined by the way spatial data experts like to work. However, we argue that the main target group for discovery portals are not spatial data experts but professionals with limited spatial knowledge, and a focus outside the spatial domain. An exploratory usability experiment was carried out in which three discovery p...

Effects of Level of Retrieval Success on Recall-Related Frontal and Medial Temporal Lobe Activations

Directory of Open Access Journals (Sweden)

Daniela Montaldi

2002-01-01

Full Text Available Brain dedicated single photon emission computed tomography (SPECT was used to compare the neuroactivation produced by the cued recall of response words in a set of studied word pairs with that produced by the cued retrieval of words semantically related to unstudied stimulus words. Six of the 12 subjects scanned were extensively trained so as to have good memory of the studied pairs and the remaining six were minimally trained so as to have poor memory. When comparing episodic with semantic retrieval, the well-trained subjects showed significant left medial temporal lobe activation, which was also significantly greater than that shown by the poorly trained subjects, who failed to show significant medial temporal lobe activation. In contrast, the poorly trained subjects showed significant bilateral frontal lobe activation, which was significantly greater than that shown by the well-trained subjects who failed to show significant frontal lobe activation. The frontal activations occurred mainly in the dorsolateral region, but extended into the ventrolateral and, to a lesser extent, the frontal polar regions. It is argued that whereas the medial temporal lobe activation increased as the proportion of response words successfully recalled increased, the bilateral frontal lobe activation increased in proportion to retrieval effort, which was greater when learning had been less good.

Temporal association between the isolation of Sabin-related poliovirus vaccine strains and the Guillain-Barré syndrome

OpenAIRE

Friedrich, F.; Filippis, A. M. B.; Schatzmayr, H. G.

1996-01-01

Thirty eight paralysis cases classified as Guillain-Barré syndrome (GBS) in Brazil were analysed. In all these cases Sabin-related poliovirus vaccine strains were isolated. In most of the cases the last vaccine dose was given months or years before the onset of GBS, suggesting a persistent infection or the transmission of the Sabin-related strains to the patients. The isolation of Sabin-related strains from GBS cases some days or weeks after the onset of the disease, demonstrated a temporal a...

Detection of whole-brain abnormalities in temporal lobe epilepsy using tensor-based morphometry with DARTEL

Science.gov (United States)

Li, Wenjing; He, Huiguang; Lu, Jingjing; Lv, Bin; Li, Meng; Jin, Zhengyu

2009-10-01

Tensor-based morphometry (TBM) is an automated technique for detecting the anatomical differences between populations by examining the gradients of the deformation fields used to nonlinearly warp MR images. The purpose of this study was to investigate the whole-brain volume changes between the patients with unilateral temporal lobe epilepsy (TLE) and the controls using TBM with DARTEL, which could achieve more accurate inter-subject registration of brain images. T1-weighted images were acquired from 21 left-TLE patients, 21 right-TLE patients and 21 healthy controls, which were matched in age and gender. The determinants of the gradient of deformation fields at voxel level were obtained to quantify the expansion or contraction for individual images relative to the template, and then logarithmical transformation was applied on it. A whole brain analysis was performed using general lineal model (GLM), and the multiple comparison was corrected by false discovery rate (FDR) with pleft-TLE patients, significant volume reductions were found in hippocampus, cingulate gyrus, precentral gyrus, right temporal lobe and cerebellum. These results potentially support the utility of TBM with DARTEL to study the structural changes between groups.

19 CFR 354.10 - Discovery.

Science.gov (United States)

2010-04-01

... 19 Customs Duties 3 2010-04-01 2010-04-01 false Discovery. 354.10 Section 354.10 Customs Duties... ANTIDUMPING OR COUNTERVAILING DUTY ADMINISTRATIVE PROTECTIVE ORDER § 354.10 Discovery. (a) Voluntary discovery. All parties are encouraged to engage in voluntary discovery procedures regarding any matter, not...

36 CFR 1150.63 - Discovery.

Science.gov (United States)

2010-07-01

... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Discovery. 1150.63 Section... PRACTICE AND PROCEDURES FOR COMPLIANCE HEARINGS Prehearing Conferences and Discovery § 1150.63 Discovery. (a) Parties are encouraged to engage in voluntary discovery procedures. For good cause shown under...

37 CFR 11.52 - Discovery.

Science.gov (United States)

2010-07-01

... 37 Patents, Trademarks, and Copyrights 1 2010-07-01 2010-07-01 false Discovery. 11.52 Section 11... Disciplinary Proceedings; Jurisdiction, Sanctions, Investigations, and Proceedings § 11.52 Discovery. Discovery... establishes that discovery is reasonable and relevant, the hearing officer, under such conditions as he or she...

Temporal focus, temporal distance, and mind-wandering valence: Results from an experience sampling and an experimental study.

Science.gov (United States)

Spronken, Maitta; Holland, Rob W; Figner, Bernd; Dijksterhuis, Ap

2016-04-01

When mind-wandering, people may think about events that happened in the past, or events that may happen in the future. Using experience sampling, we first aimed to replicate the finding that future-oriented thoughts show a greater positivity bias than past-oriented thoughts. Furthermore, we investigated whether there is a relation between the temporal distance of past- and future-oriented thoughts and the frequency of positive thoughts, a factor that has received little attention in previous work. Second, we experimentally investigated the relation between temporal focus, temporal distance, and thought valence. Both studies showed that future-oriented thoughts were more positive compared to past-oriented thoughts. Regarding temporal distance, thoughts about the distant past and future were more positive than thoughts about the near past and future in the experiment. However, the experience sampling study did not provide clear insight into this relation. Potential theoretical and methodological explanations for these findings are discussed. Copyright © 2016 Elsevier Inc. All rights reserved.

Usability of Discovery Portals

NARCIS (Netherlands)

Bulens, J.D.; Vullings, L.A.E.; Houtkamp, J.M.; Vanmeulebrouk, B.

2013-01-01

As INSPIRE progresses to be implemented in the EU, many new discovery portals are built to facilitate finding spatial data. Currently the structure of the discovery portals is determined by the way spatial data experts like to work. However, we argue that the main target group for discovery portals

14 CFR 16.213 - Discovery.

Science.gov (United States)

2010-01-01

... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Discovery. 16.213 Section 16.213... PRACTICE FOR FEDERALLY-ASSISTED AIRPORT ENFORCEMENT PROCEEDINGS Hearings § 16.213 Discovery. (a) Discovery... discovery permitted by this section if a party shows that— (1) The information requested is cumulative or...

28 CFR 76.21 - Discovery.

Science.gov (United States)

2010-07-01

... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Discovery. 76.21 Section 76.21 Judicial... POSSESSION OF CERTAIN CONTROLLED SUBSTANCES § 76.21 Discovery. (a) Scope. Discovery under this part covers... as a general guide for discovery practices in proceedings before the Judge. However, unless otherwise...

Detailed immunohistochemical characterization of temporal and spatial progression of Alzheimer's disease-related pathologies in male triple-transgenic mice

Directory of Open Access Journals (Sweden)

Bowers William J

2008-08-01

Full Text Available Abstract Background Several transgenic animal models genetically predisposed to develop Alzheimer's disease (AD-like pathology have been engineered to facilitate the study of disease pathophysiology and the vetting of potential disease-modifying therapeutics. The triple transgenic mouse model of AD (3xTg-AD harbors three AD-related genetic loci: human PS1M146V, human APPswe, and human tauP301L. These mice develop both amyloid plaques and neurofibrillary tangle-like pathology in a progressive and age-dependent manner, while these pathological hallmarks are predominantly restricted to the hippocampus, amygdala, and the cerebral cortex the main foci of AD neuropathology in humans. This model represents, at present, one of the most advanced preclinical tools available and is being employed ever increasingly in the study of mechanisms underlying AD, yet a detailed regional and temporal assessment of the subtleties of disease-related pathologies has not been reported. Methods and results In this study, we immunohistochemically documented the evolution of AD-related transgene expression, amyloid deposition, tau phosphorylation, astrogliosis, and microglial activation throughout the hippocampus, entorhinal cortex, primary motor cortex, and amygdala over a 26-month period in male 3xTg-AD mice. Intracellular amyloid-beta accumulation is detectable the earliest of AD-related pathologies, followed temporally by phospho-tau, extracellular amyloid-beta, and finally paired helical filament pathology. Pathology appears to be most severe in medial and caudal hippocampus. While astrocytic staining remains relatively constant at all ages and regions assessed, microglial activation appears to progressively increase temporally, especially within the hippocampal formation. Conclusion These data fulfill an unmet need in the ever-widening community of investigators studying 3xTg-AD mice and provide a foundation upon which to design future experiments that seek to

Applying Hierarchical Task Analysis Method to Discovery Layer Evaluation

Directory of Open Access Journals (Sweden)

Marlen Promann

2015-03-01

Full Text Available Libraries are implementing discovery layers to offer better user experiences. While usability tests have been helpful in evaluating the success or failure of implementing discovery layers in the library context, the focus has remained on its relative interface benefits over the traditional federated search. The informal site- and context specific usability tests have offered little to test the rigor of the discovery layers against the user goals, motivations and workflow they have been designed to support. This study proposes hierarchical task analysis (HTA as an important complementary evaluation method to usability testing of discovery layers. Relevant literature is reviewed for the discovery layers and the HTA method. As no previous application of HTA to the evaluation of discovery layers was found, this paper presents the application of HTA as an expert based and workflow centered (e.g. retrieving a relevant book or a journal article method to evaluating discovery layers. Purdue University’s Primo by Ex Libris was used to map eleven use cases as HTA charts. Nielsen’s Goal Composition theory was used as an analytical framework to evaluate the goal carts from two perspectives: a users’ physical interactions (i.e. clicks, and b user’s cognitive steps (i.e. decision points for what to do next. A brief comparison of HTA and usability test findings is offered as a way of conclusion.

40 CFR 27.21 - Discovery.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Discovery. 27.21 Section 27.21... Discovery. (a) The following types of discovery are authorized: (1) Requests for production of documents for..., discovery is available only as ordered by the presiding officer. The presiding officer shall regulate the...

37 CFR 41.150 - Discovery.

Science.gov (United States)

2010-07-01

... 37 Patents, Trademarks, and Copyrights 1 2010-07-01 2010-07-01 false Discovery. 41.150 Section 41... COMMERCE PRACTICE BEFORE THE BOARD OF PATENT APPEALS AND INTERFERENCES Contested Cases § 41.150 Discovery. (a) Limited discovery. A party is not entitled to discovery except as authorized in this subpart. The...

14 CFR 13.220 - Discovery.

Science.gov (United States)

2010-01-01

... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Discovery. 13.220 Section 13.220... INVESTIGATIVE AND ENFORCEMENT PROCEDURES Rules of Practice in FAA Civil Penalty Actions § 13.220 Discovery. (a) Initiation of discovery. Any party may initiate discovery described in this section, without the consent or...

49 CFR 604.38 - Discovery.

Science.gov (United States)

2010-10-01

... 49 Transportation 7 2010-10-01 2010-10-01 false Discovery. 604.38 Section 604.38 Transportation... TRANSPORTATION CHARTER SERVICE Hearings. § 604.38 Discovery. (a) Permissible forms of discovery shall be within the discretion of the PO. (b) The PO shall limit the frequency and extent of discovery permitted by...

24 CFR 26.18 - Discovery.

Science.gov (United States)

2010-04-01

... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Discovery. 26.18 Section 26.18... PROCEDURES Hearings Before Hearing Officers Discovery § 26.18 Discovery. (a) General. The parties are encouraged to engage in voluntary discovery procedures, which may commence at any time after an answer has...

42 CFR 426.532 - Discovery.

Science.gov (United States)

2010-10-01

... 42 Public Health 3 2010-10-01 2010-10-01 false Discovery. 426.532 Section 426.532 Public Health... § 426.532 Discovery. (a) General rule. If the Board orders discovery, the Board must establish a reasonable timeframe for discovery. (b) Protective order—(1) Request for a protective order. Any party...

49 CFR 1503.633 - Discovery.

Science.gov (United States)

2010-10-01

... 49 Transportation 9 2010-10-01 2010-10-01 false Discovery. 1503.633 Section 1503.633... Rules of Practice in TSA Civil Penalty Actions § 1503.633 Discovery. (a) Initiation of discovery. Any party may initiate discovery described in this section, without the consent or approval of the ALJ, at...

14 CFR 1264.120 - Discovery.

Science.gov (United States)

2010-01-01

... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Discovery. 1264.120 Section 1264.120... PENALTIES ACT OF 1986 § 1264.120 Discovery. (a) The following types of discovery are authorized: (1..., discovery is available only as ordered by the presiding officer. The presiding officer shall regulate the...

24 CFR 26.42 - Discovery.

Science.gov (United States)

2010-04-01

... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Discovery. 26.42 Section 26.42... PROCEDURES Hearings Pursuant to the Administrative Procedure Act Discovery § 26.42 Discovery. (a) General. The parties are encouraged to engage in voluntary discovery procedures, which may commence at any time...

49 CFR 386.37 - Discovery.

Science.gov (United States)

2010-10-01

... 49 Transportation 5 2010-10-01 2010-10-01 false Discovery. 386.37 Section 386.37 Transportation... and Hearings § 386.37 Discovery. (a) Parties may obtain discovery by one or more of the following...; and requests for admission. (b) Discovery may not commence until the matter is pending before the...

29 CFR 1955.32 - Discovery.

Science.gov (United States)

2010-07-01

... 29 Labor 9 2010-07-01 2010-07-01 false Discovery. 1955.32 Section 1955.32 Labor Regulations...) PROCEDURES FOR WITHDRAWAL OF APPROVAL OF STATE PLANS Preliminary Conference and Discovery § 1955.32 Discovery... allow discovery by any other appropriate procedure, such as by interrogatories upon a party or request...

Optimizing Temporal Queries: Efficient Handling of Duplicates

DEFF Research Database (Denmark)

Toman, David; Bowman, Ivan Thomas

2001-01-01

, these query languages are implemented by translating temporal queries into standard relational queries. However, the compiled queries are often quite cumbersome and expensive to execute even using state-of-the- art relational products. This paper presents an optimization technique that produces more efficient...... translated SQL queries by taking into account the properties of the encoding used for temporal attributes. For concreteness, this translation technique is presented in the context of SQL/TP; however, these techniques are also applicable to other temporal query languages....

Comparing the temporal dynamics of thematic and taxonomic processing using event-related potentials.

Directory of Open Access Journals (Sweden)

Olivera Savic

Full Text Available We report the results of a study comparing the temporal dynamics of thematic and taxonomic knowledge activation in a picture-word priming paradigm using event-related potentials. Although we found no behavioral differences between thematic and taxonomic processing, ERP data revealed distinct patterns of N400 and P600 amplitude modulation for thematic and taxonomic priming. Thematically related target stimuli elicited less negativity than taxonomic targets between 280-460 ms after stimulus onset, suggesting easier semantic processing of thematic than taxonomic relationships. Moreover, P600 mean amplitude was significantly increased for taxonomic targets between 520-600 ms, consistent with a greater need for stimulus reevaluation in that condition. These results offer novel evidence in favor of a dissociation between thematic and taxonomic thinking in the early phases of conceptual evaluation.

Comparing the temporal dynamics of thematic and taxonomic processing using event-related potentials.

Science.gov (United States)

Savic, Olivera; Savic, Andrej M; Kovic, Vanja

2017-01-01

We report the results of a study comparing the temporal dynamics of thematic and taxonomic knowledge activation in a picture-word priming paradigm using event-related potentials. Although we found no behavioral differences between thematic and taxonomic processing, ERP data revealed distinct patterns of N400 and P600 amplitude modulation for thematic and taxonomic priming. Thematically related target stimuli elicited less negativity than taxonomic targets between 280-460 ms after stimulus onset, suggesting easier semantic processing of thematic than taxonomic relationships. Moreover, P600 mean amplitude was significantly increased for taxonomic targets between 520-600 ms, consistent with a greater need for stimulus reevaluation in that condition. These results offer novel evidence in favor of a dissociation between thematic and taxonomic thinking in the early phases of conceptual evaluation.

Optimization of temporal networks under uncertainty

CERN Document Server

Wiesemann, Wolfram

2012-01-01

Many decision problems in Operations Research are defined on temporal networks, that is, workflows of time-consuming tasks whose processing order is constrained by precedence relations. For example, temporal networks are used to model projects, computer applications, digital circuits and production processes. Optimization problems arise in temporal networks when a decision maker wishes to determine a temporal arrangement of the tasks and/or a resource assignment that optimizes some network characteristic (e.g. the time required to complete all tasks). The parameters of these optimization probl

42 CFR 426.432 - Discovery.

Science.gov (United States)

2010-10-01

... 42 Public Health 3 2010-10-01 2010-10-01 false Discovery. 426.432 Section 426.432 Public Health... § 426.432 Discovery. (a) General rule. If the ALJ orders discovery, the ALJ must establish a reasonable timeframe for discovery. (b) Protective order—(1) Request for a protective order. Any party receiving a...

10 CFR 13.21 - Discovery.

Science.gov (United States)

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false Discovery. 13.21 Section 13.21 Energy NUCLEAR REGULATORY COMMISSION PROGRAM FRAUD CIVIL REMEDIES § 13.21 Discovery. (a) The following types of discovery are...) Unless mutually agreed to by the parties, discovery is available only as ordered by the ALJ. The ALJ...

49 CFR 1121.2 - Discovery.

Science.gov (United States)

2010-10-01

... 49 Transportation 8 2010-10-01 2010-10-01 false Discovery. 1121.2 Section 1121.2 Transportation... TRANSPORTATION RULES OF PRACTICE RAIL EXEMPTION PROCEDURES § 1121.2 Discovery. Discovery shall follow the procedures set forth at 49 CFR part 1114, subpart B. Discovery may begin upon the filing of the petition for...

38 CFR 42.21 - Discovery.

Science.gov (United States)

2010-07-01

... 38 Pensions, Bonuses, and Veterans' Relief 2 2010-07-01 2010-07-01 false Discovery. 42.21 Section... IMPLEMENTING THE PROGRAM FRAUD CIVIL REMEDIES ACT § 42.21 Discovery. (a) The following types of discovery are... creation of a document. (c) Unless mutually agreed to by the parties, discovery is available only as...

31 CFR 10.71 - Discovery.

Science.gov (United States)

2010-07-01

... 31 Money and Finance: Treasury 1 2010-07-01 2010-07-01 false Discovery. 10.71 Section 10.71 Money... SERVICE Rules Applicable to Disciplinary Proceedings § 10.71 Discovery. (a) In general. Discovery may be... relevance, materiality and reasonableness of the requested discovery and subject to the requirements of § 10...

39 CFR 955.15 - Discovery.

Science.gov (United States)

2010-07-01

... 39 Postal Service 1 2010-07-01 2010-07-01 false Discovery. 955.15 Section 955.15 Postal Service... APPEALS § 955.15 Discovery. (a) The parties are encouraged to engage in voluntary discovery procedures. In connection with any deposition or other discovery procedure, the Board may issue any order which justice...

43 CFR 35.21 - Discovery.

Science.gov (United States)

2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Discovery. 35.21 Section 35.21 Public... AND STATEMENTS § 35.21 Discovery. (a) The following types of discovery are authorized: (1) Requests...) Unless mutually agreed to by the parties, discovery is available only as ordered by the ALJ. The ALJ...

Temporal and spatial variability in the aviation NOx-related O3 impact

International Nuclear Information System (INIS)

Gilmore, Christopher K; Barrett, Steven R H; Koo, Jamin; Wang, Qiqi

2013-01-01

Aviation NO x emissions promote tropospheric ozone formation, which is linked to climate warming and adverse health effects. Modeling studies have quantified the relative impact of aviation NO x on O 3 in large geographic regions. As these studies have applied forward modeling techniques, it has not been possible to attribute O 3 formation to individual flights. Here we apply the adjoint of the global chemistry–transport model GEOS-Chem to assess the temporal and spatial variability in O 3 production due to aviation NO x emissions, which is the first application of an adjoint to this problem. We find that total aviation NO x emitted in October causes 40% more O 3 than in April and that Pacific aviation emissions could cause 4–5 times more tropospheric O 3 per unit NO x than European or North American emissions. Using this sensitivity approach, the O 3 burden attributable to 83 000 unique scheduled civil flights is computed individually. We find that the ten highest total O 3 -producing flights have origins or destinations in New Zealand or Australia. The top ranked O 3 -producing flights normalized by fuel burn cause 157 times more normalized O 3 formation than the bottom ranked ones. These results show significant spatial and temporal heterogeneity in environmental impacts of aviation NO x emissions. (letter)

An Ontology for Description of Drug Discovery Investigations

Directory of Open Access Journals (Sweden)

Qi Da

2010-12-01

Full Text Available The paper presents an ontology for the description of Drug Discovery Investigation (DDI. This has been developed through the use of a Robot Scientist “Eve”, and in consultation with industry. DDI aims to define the principle entities and the relations in the research and development phase of the drug discovery pipeline. DDI is highly transferable and extendable due to its adherence to accepted standards, and compliance with existing ontology resources. This enables DDI to be integrated with such related ontologies as the Vaccine Ontology, the Advancing Clinico-Genomic Trials on Cancer Master Ontology, etc. DDI is available at http://purl.org/ddi/wikipedia or http://purl.org/ddi/home

13 CFR 134.213 - Discovery.

Science.gov (United States)

2010-01-01

... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Discovery. 134.213 Section 134.213... OFFICE OF HEARINGS AND APPEALS Rules of Practice for Most Cases § 134.213 Discovery. (a) Motion. A party may obtain discovery only upon motion, and for good cause shown. (b) Forms. The forms of discovery...

31 CFR 16.21 - Discovery.

Science.gov (United States)

2010-07-01

... 31 Money and Finance: Treasury 1 2010-07-01 2010-07-01 false Discovery. 16.21 Section 16.21 Money... FRAUD CIVIL REMEDIES ACT OF 1986 § 16.21 Discovery. (a) The following types of discovery are authorized... to require the creation of a document. (c) Unless mutually agreed to by the parties, discovery is...

Annotating temporal information in clinical narratives.

Science.gov (United States)

Sun, Weiyi; Rumshisky, Anna; Uzuner, Ozlem

2013-12-01

Temporal information in clinical narratives plays an important role in patients' diagnosis, treatment and prognosis. In order to represent narrative information accurately, medical natural language processing (MLP) systems need to correctly identify and interpret temporal information. To promote research in this area, the Informatics for Integrating Biology and the Bedside (i2b2) project developed a temporally annotated corpus of clinical narratives. This corpus contains 310 de-identified discharge summaries, with annotations of clinical events, temporal expressions and temporal relations. This paper describes the process followed for the development of this corpus and discusses annotation guideline development, annotation methodology, and corpus quality. Copyright © 2013 Elsevier Inc. All rights reserved.

A search for temporal changes on Pluto and Charon

Science.gov (United States)

Hofgartner, J. D.; Buratti, B. J.; Devins, S. L.; Beyer, R. A.; Schenk, P.; Stern, S. A.; Weaver, H. A.; Olkin, C. B.; Cheng, A.; Ennico, K.; Lauer, T. R.; McKinnon, W. B.; Spencer, J.; Young, L. A.; New Horizons Science Team

2018-03-01

A search for temporal changes on Pluto and Charon was motivated by (1) the discovery of young surfaces in the Pluto system that imply ongoing or recent geologic activity, (2) the detection of active plumes on Triton during the Voyager 2 flyby, and (3) the abundant and detailed information that observing geologic processes in action provides about the processes. A thorough search for temporal changes using New Horizons images was completed. Images that covered the same region were blinked and manually inspected for any differences in appearance. The search included full-disk images such that all illuminated regions of both bodies were investigated and higher resolution images such that parts of the encounter hemispheres were investigated at finer spatial scales. Changes of appearance between different images were observed but in all cases were attributed to variability of the imaging parameters (especially geometry) or artifacts. No differences of appearance that are strongly indicative of a temporal change were found on the surface or in the atmosphere of either Pluto or Charon. Limits on temporal changes as a function of spatial scale and temporal interval during the New Horizons encounter are determined. The longest time interval constraint is one Pluto/Charon rotation period (∼6.4 Earth days). Contrast reversal and high-phase bright features that change in appearance with solar phase angle are identified. The change of appearance of these features is most likely due to the change in phase angle rather than a temporal change. Had active plumes analogous to the plumes discovered on Triton been present on the encounter hemispheres of either Pluto or Charon, they would have been detected. The absence of active plumes may be due to temporal variability (i.e., plumes do occur but none were active on the encounter hemispheres during the epoch of the New Horizons encounter) or because plumes do not occur. Several dark streak features that may be deposits from past

Citation Discovery Tools for Conducting Adaptive Meta-analyses to Update Systematic Reviews.

Science.gov (United States)

Bae, Jong-Myon; Kim, Eun Hee

2016-03-01

The systematic review (SR) is a research methodology that aims to synthesize related evidence. Updating previously conducted SRs is necessary when new evidence has been produced, but no consensus has yet emerged on the appropriate update methodology. The authors have developed a new SR update method called 'adaptive meta-analysis' (AMA) using the 'cited by', 'similar articles', and 'related articles' citation discovery tools in the PubMed and Scopus databases. This study evaluates the usefulness of these citation discovery tools for updating SRs. Lists were constructed by applying the citation discovery tools in the two databases to the articles analyzed by a published SR. The degree of overlap between the lists and distribution of excluded results were evaluated. The articles ultimately selected for the SR update meta-analysis were found in the lists obtained from the 'cited by' and 'similar' tools in PubMed. Most of the selected articles appeared in both the 'cited by' lists in Scopus and PubMed. The Scopus 'related' tool did not identify the appropriate articles. The AMA, which involves using both citation discovery tools in PubMed, and optionally, the 'related' tool in Scopus, was found to be useful for updating an SR.

Temporal maps and informativeness in associative learning.

Science.gov (United States)

Balsam, Peter D; Gallistel, C Randy

2009-02-01

Neurobiological research on learning assumes that temporal contiguity is essential for association formation, but what constitutes temporal contiguity has never been specified. We review evidence that learning depends, instead, on learning a temporal map. Temporal relations between events are encoded even from single experiences. The speed with which an anticipatory response emerges is proportional to the informativeness of the encoded relation between a predictive stimulus or event and the event it predicts. This principle yields a quantitative account of the heretofore undefined, but theoretically crucial, concept of temporal pairing, an account in quantitative accord with surprising experimental findings. The same principle explains the basic results in the cue competition literature, which motivated the Rescorla-Wagner model and most other contemporary models of associative learning. The essential feature of a memory mechanism in this account is its ability to encode quantitative information.

Full-fledged temporal processing: bridging the gap between deep linguistic processing and temporal extraction

Directory of Open Access Journals (Sweden)

Francisco Costa

2013-07-01

Full Text Available The full-fledged processing of temporal information presents specific challenges. These difficulties largely stem from the fact that the temporal meaning conveyed by grammatical means interacts with many extra-linguistic factors (world knowledge, causality, calendar systems, reasoning. This article proposes a novel approach to this problem, based on a hybrid strategy that explores the complementarity of the symbolic and probabilistic methods. A specialized temporal extraction system is combined with a deep linguistic processing grammar. The temporal extraction system extracts eventualities, times and dates mentioned in text, and also temporal relations between them, in line with the tasks of the recent TempEval challenges; and uses machine learning techniques to draw from different sources of information (grammatical and extra-grammatical even if it is not explicitly known how these combine to produce the final temporal meaning being expressed. In turn, the deep computational grammar delivers richer truth-conditional meaning representations of input sentences, which include a principled representation of temporal information, on which higher level tasks, including reasoning, can be based. These deep semantic representations are extended and improved according to the output of the aforementioned temporal extraction module. The prototype implemented shows performance results that increase the quality of the temporal meaning representations and are better than the performance of each of the two components in isolation.

Mass spectrometry-driven drug discovery for development of herbal medicine.

Science.gov (United States)

Zhang, Aihua; Sun, Hui; Wang, Xijun

2018-05-01

Herbal medicine (HM) has made a major contribution to the drug discovery process with regard to identifying products compounds. Currently, more attention has been focused on drug discovery from natural compounds of HM. Despite the rapid advancement of modern analytical techniques, drug discovery is still a difficult and lengthy process. Fortunately, mass spectrometry (MS) can provide us with useful structural information for drug discovery, has been recognized as a sensitive, rapid, and high-throughput technology for advancing drug discovery from HM in the post-genomic era. It is essential to develop an efficient, high-quality, high-throughput screening method integrated with an MS platform for early screening of candidate drug molecules from natural products. We have developed a new chinmedomics strategy reliant on MS that is capable of capturing the candidate molecules, facilitating their identification of novel chemical structures in the early phase; chinmedomics-guided natural product discovery based on MS may provide an effective tool that addresses challenges in early screening of effective constituents of herbs against disease. This critical review covers the use of MS with related techniques and methodologies for natural product discovery, biomarker identification, and determination of mechanisms of action. It also highlights high-throughput chinmedomics screening methods suitable for lead compound discovery illustrated by recent successes. © 2016 Wiley Periodicals, Inc.

A KNOWLEDGE DISCOVERY STRATEGY FOR RELATING SEA SURFACE TEMPERATURES TO FREQUENCIES OF TROPICAL STORMS AND GENERATING PREDICTIONS OF HURRICANES UNDER 21ST-CENTURY GLOBAL WARMING SCENARIOS

Data.gov (United States)

National Aeronautics and Space Administration — A KNOWLEDGE DISCOVERY STRATEGY FOR RELATING SEA SURFACE TEMPERATURES TO FREQUENCIES OF TROPICAL STORMS AND GENERATING PREDICTIONS OF HURRICANES UNDER 21ST-CENTURY...

Temporal network epidemiology

CERN Document Server

Holme, Petter

2017-01-01

This book covers recent developments in epidemic process models and related data on temporally varying networks. It is widely recognized that contact networks are indispensable for describing, understanding, and intervening to stop the spread of infectious diseases in human and animal populations; “network epidemiology” is an umbrella term to describe this research field. More recently, contact networks have been recognized as being highly dynamic. This observation, also supported by an increasing amount of new data, has led to research on temporal networks, a rapidly growing area. Changes in network structure are often informed by epidemic (or other) dynamics, in which case they are referred to as adaptive networks. This volume gathers contributions by prominent authors working in temporal and adaptive network epidemiology, a field essential to understanding infectious diseases in real society.

Cyber-Enabled Scientific Discovery

International Nuclear Information System (INIS)

Chan, Tony; Jameson, Leland

2007-01-01

It is often said that numerical simulation is third in the group of three ways to explore modern science: theory, experiment and simulation. Carefully executed modern numerical simulations can, however, be considered at least as relevant as experiment and theory. In comparison to physical experimentation, with numerical simulation one has the numerically simulated values of every field variable at every grid point in space and time. In comparison to theory, with numerical simulation one can explore sets of very complex non-linear equations such as the Einstein equations that are very difficult to investigate theoretically. Cyber-enabled scientific discovery is not just about numerical simulation but about every possible issue related to scientific discovery by utilizing cyberinfrastructure such as the analysis and storage of large data sets, the creation of tools that can be used by broad classes of researchers and, above all, the education and training of a cyber-literate workforce

Vertical, horizontal, and temporal changes in temperature in the Atlantis II and Discovery hot brine pools, Red Sea

KAUST Repository

Swift, Stephen A.

2012-06-01

In October 2008, we measured temperature and salinity in hot, hypersaline brine filling the Atlantis II and Discovery Deeps on the Red Sea spreading center west of Jeddah, Saudi Arabia. In agreement with previous observations in the Atlantis II Deep, we found a stack of four convective layers with vertically uniform temperature profiles separated by thin interfaces with high vertical temperature gradients. Temperature in the thick lower convective layer in the Atlantis II Deep continued to slowly increase at 0.1 °C/year since the last observations in 1997. Previously published data show that the temperature of all four convective layers increased since the 1960s at the same rate, from which we infer that diffusive vertical heat flux between convective layers is rapid on time scales of 3-5 years and, thus, heat is lost from the brine pools to overlying Red Sea Deep Water. Heat budgets suggest that the heat flux from hydrothermal venting has decreased from 0.54. GW to 0.18. GW since 1966. A tow-yo survey found that temperature in the upper convective layers changes about 0.2 °C over 5-6. km but the temperature in the lower brine layer remains constant. Temperature in the lower convective layer in the Discovery Deep remains unchanged at 48 °C. To explain these results, we hypothesize that heat flux from a hydrothermal vent in the floor of the Discovery Deep has been stable for 40 years, whereas temperature of the brine in the Atlantis II Deep is adjusting to the change in hydrothermal heat flux from the vent in the Southwest Basin. We found no changes in the upper transition layer at 1900-1990. m depth that appeared between 1976 and 1992 and suggest that this layer originated from the seafloor elsewhere in the rift. © 2012 Elsevier Ltd.

Genome-Wide Temporal Expression Profiling in Caenorhabditis elegans Identifies a Core Gene Set Related to Long-Term Memory.

Science.gov (United States)

Freytag, Virginie; Probst, Sabine; Hadziselimovic, Nils; Boglari, Csaba; Hauser, Yannick; Peter, Fabian; Gabor Fenyves, Bank; Milnik, Annette; Demougin, Philippe; Vukojevic, Vanja; de Quervain, Dominique J-F; Papassotiropoulos, Andreas; Stetak, Attila

2017-07-12

The identification of genes related to encoding, storage, and retrieval of memories is a major interest in neuroscience. In the current study, we analyzed the temporal gene expression changes in a neuronal mRNA pool during an olfactory long-term associative memory (LTAM) in Caenorhabditis elegans hermaphrodites. Here, we identified a core set of 712 (538 upregulated and 174 downregulated) genes that follows three distinct temporal peaks demonstrating multiple gene regulation waves in LTAM. Compared with the previously published positive LTAM gene set (Lakhina et al., 2015), 50% of the identified upregulated genes here overlap with the previous dataset, possibly representing stimulus-independent memory-related genes. On the other hand, the remaining genes were not previously identified in positive associative memory and may specifically regulate aversive LTAM. Our results suggest a multistep gene activation process during the formation and retrieval of long-term memory and define general memory-implicated genes as well as conditioning-type-dependent gene sets. SIGNIFICANCE STATEMENT The identification of genes regulating different steps of memory is of major interest in neuroscience. Identification of common memory genes across different learning paradigms and the temporal activation of the genes are poorly studied. Here, we investigated the temporal aspects of Caenorhabditis elegans gene expression changes using aversive olfactory associative long-term memory (LTAM) and identified three major gene activation waves. Like in previous studies, aversive LTAM is also CREB dependent, and CREB activity is necessary immediately after training. Finally, we define a list of memory paradigm-independent core gene sets as well as conditioning-dependent genes. Copyright © 2017 the authors 0270-6474/17/376661-12$15.00/0.

The relation of learners' motivation with the process of collaborative scientific discovery learning

NARCIS (Netherlands)

Saab, N.; van Joolingen, W.R.; van Hout-Wolters, B.H.A.M.

2009-01-01

In this study, we investigated the influence of individual learners' motivation on the collaborative discovery learning process. In this we distinguished the motivation of the individual learners and had eye for the composition of groups, which could be homogeneous or heterogeneous in terms of

Temporal dynamics of conflict monitoring and the effects of one or two conflict sources on error-(related) negativity.

Science.gov (United States)

Armbrecht, Anne-Simone; Wöhrmann, Anne; Gibbons, Henning; Stahl, Jutta

2010-09-01

The present electrophysiological study investigated the temporal development of response conflict and the effects of diverging conflict sources on error(-related) negativity (Ne). Eighteen participants performed a combined stop-signal flanker task, which was comprised of two different conflict sources: a left-right and a go-stop response conflict. It is assumed that the Ne reflects the activity of a conflict monitoring system and thus increases according to (i) the number of conflict sources and (ii) the temporal development of the conflict activity. No increase of the Ne amplitude after double errors (comprising two conflict sources) as compared to hand- and stop-errors (comprising one conflict source) was found, whereas a higher Ne amplitude was observed after a delayed stop-signal onset. The results suggest that the Ne is not sensitive to an increase in the number of conflict sources, but to the temporal dynamics of a go-stop response conflict. Copyright (c) 2010 Elsevier B.V. All rights reserved.

The Emergence of Visual Awareness: Temporal Dynamics in Relation to Task and Mask Type

Science.gov (United States)

Kiefer, Markus; Kammer, Thomas

2017-01-01

One aspect of consciousness phenomena, the temporal emergence of visual awareness, has been subject of a controversial debate. How can visual awareness, that is the experiential quality of visual stimuli, be characterized best? Is there a sharp discontinuous or dichotomous transition between unaware and fully aware states, or does awareness emerge gradually encompassing intermediate states? Previous studies yielded conflicting results and supported both dichotomous and gradual views. It is well conceivable that these conflicting results are more than noise, but reflect the dynamic nature of the temporal emergence of visual awareness. Using a psychophysical approach, the present research tested whether the emergence of visual awareness is context-dependent with a temporal two-alternative forced choice task. During backward masking of word targets, it was assessed whether the relative temporal sequence of stimulus thresholds is modulated by the task (stimulus presence, letter case, lexical decision, and semantic category) and by mask type. Four masks with different similarity to the target features were created. Psychophysical functions were then fitted to the accuracy data in the different task conditions as a function of the stimulus mask SOA in order to determine the inflection point (conscious threshold of each feature) and slope of the psychophysical function (transition from unaware to aware within each feature). Depending on feature-mask similarity, thresholds in the different tasks were highly dispersed suggesting a graded transition from unawareness to awareness or had less differentiated thresholds indicating that clusters of features probed by the tasks quite simultaneously contribute to the percept. The latter observation, although not compatible with the notion of a sharp all-or-none transition between unaware and aware states, suggests a less gradual or more discontinuous emergence of awareness. Analyses of slopes of the fitted psychophysical functions

Decades of Discovery

Science.gov (United States)

2011-06-01

For the past two-and-a-half decades, the Office of Science at the U.S. Department of Energy has been at the forefront of scientific discovery. Over 100 important discoveries supported by the Office of Science are represented in this document.

Discovery and the atom

International Nuclear Information System (INIS)

1989-01-01

''Discovery and the Atom'' tells the story of the founding of nuclear physics. This programme looks at nuclear physics up to the discovery of the neutron in 1932. Animation explains the science of the classic experiments, such as the scattering of alpha particles by Rutherford and the discovery of the nucleus. Archive film shows the people: Lord Rutherford, James Chadwick, Marie Curie. (author)

Inseparability of science history and discovery

Directory of Open Access Journals (Sweden)

J. M. Herndon

2010-04-01

Full Text Available Science is very much a logical progression through time. Progressing along a logical path of discovery is rather like following a path through the wilderness. Occasionally the path splits, presenting a choice; the correct logical interpretation leads to further progress, the wrong choice leads to confusion. By considering deeply the relevant science history, one might begin to recognize past faltering in the logical progression of observations and ideas and, perhaps then, to discover new, more precise understanding. The following specific examples of science faltering are described from a historical perspective: (1 Composition of the Earth's inner core; (2 Giant planet internal energy production; (3 Physical impossibility of Earth-core convection and Earth-mantle convection, and; (4 Thermonuclear ignition of stars. For each example, a revised logical progression is described, leading, respectively, to: (1 Understanding the endo-Earth's composition; (2 The concept of nuclear georeactor origin of geo- and planetary magnetic fields; (3 The invalidation and replacement of plate tectonics; and, (4 Understanding the basis for the observed distribution of luminous stars in galaxies. These revised logical progressions clearly show the inseparability of science history and discovery. A different and more fundamental approach to making scientific discoveries than the frequently discussed variants of the scientific method is this: An individual ponders and through tedious efforts arranges seemingly unrelated observations into a logical sequence in the mind so that causal relationships become evident and new understanding emerges, showing the path for new observations, for new experiments, for new theoretical considerations, and for new discoveries. Science history is rich in "seemingly unrelated observations" just waiting to be logically and causally related to reveal new discoveries.

Perceiving temporal regularity in music: The role of auditory event-related potentials (ERPs) in probing beat perception

NARCIS (Netherlands)

Honing, H.; Bouwer, F.L.; Háden, G.P.; Merchant, H.; de Lafuente, V.

2014-01-01

The aim of this chapter is to give an overview of how the perception of a regular beat in music can be studied in humans adults, human newborns, and nonhuman primates using event-related brain potentials (ERPs). Next to a review of the recent literature on the perception of temporal regularity in

Pathways to new drug discovery in neuropsychiatry

Directory of Open Access Journals (Sweden)

Berk Michael

2012-11-01

Full Text Available Abstract There is currently a crisis in drug discovery for neuropsychiatric disorders, with a profound, yet unexpected drought in new drug development across the spectrum. In this commentary, the sources of this dilemma and potential avenues to redress the issue are explored. These include a critical review of diagnostic issues and of selection of participants for clinical trials, and the mechanisms for identifying new drugs and new drug targets. Historically, the vast majority of agents have been discovered serendipitously or have been modifications of existing agents. Serendipitous discoveries, based on astute clinical observation or data mining, remain a valid option, as is illustrated by the suggestion in the paper by Wahlqvist and colleagues that treatment with sulfonylurea and metformin reduces the risk of affective disorder. However, the identification of agents targeting disorder-related biomarkers is currently proving particularly fruitful. There is considerable hope for genetics as a purist, pathophysiologically valid pathway to drug discovery; however, it is unclear whether the science is ready to meet this promise. Fruitful paradigms will require a break from the orthodoxy, and creativity and risk may well be the fingerprints of success. See related article http://www.biomedcentral.com/1741-7015/10/150

Temporal profile of body temperature in acute ischemic stroke: relation to infarct size and outcome.

Science.gov (United States)

Geurts, Marjolein; Scheijmans, Féline E V; van Seeters, Tom; Biessels, Geert J; Kappelle, L Jaap; Velthuis, Birgitta K; van der Worp, H Bart

2016-11-21

High body temperatures after ischemic stroke have been associated with larger infarct size, but the temporal profile of this relation is unknown. We assess the relation between temporal profile of body temperature and infarct size and functional outcome in patients with acute ischemic stroke. In 419 patients with acute ischemic stroke we assessed the relation between body temperature on admission and during the first 3 days with both infarct size and functional outcome. Infarct size was measured in milliliters on CT or MRI after 3 days. Poor functional outcome was defined as a modified Rankin Scale score ≥3 at 3 months. Body temperature on admission was not associated with infarct size or poor outcome in adjusted analyses. By contrast, each additional 1.0 °C in body temperature on day 1 was associated with 0.31 ml larger infarct size (95% confidence interval (CI) 0.04-0.59), on day 2 with 1.13 ml larger infarct size(95% CI, 0.83-1.43), and on day 3 with 0.80 ml larger infarct size (95% CI, 0.48-1.12), in adjusted linear regression analyses. Higher peak body temperatures on days two and three were also associated with poor outcome (adjusted relative risks per additional 1.0 °C in body temperature, 1.52 (95% CI, 1.17-1.99) and 1.47 (95% CI, 1.22-1.77), respectively). Higher peak body temperatures during the first days after ischemic stroke, rather than on admission, are associated with larger infarct size and poor functional outcome. This suggests that prevention of high temperatures may improve outcome if continued for at least 3 days.

29 CFR 2700.56 - Discovery; general.

Science.gov (United States)

2010-07-01

...(c) or 111 of the Act has been filed. 30 U.S.C. 815(c) and 821. (e) Completion of discovery... 29 Labor 9 2010-07-01 2010-07-01 false Discovery; general. 2700.56 Section 2700.56 Labor... Hearings § 2700.56 Discovery; general. (a) Discovery methods. Parties may obtain discovery by one or more...

Social Relationship Discovery Via Call Records

Directory of Open Access Journals (Sweden)

Zhao Wen-Zhe

2017-01-01

Full Text Available Telecom users constitute a huge, but relatively sparse social network. Community discovery has been a research topic of data mining. Traditional algorithms are greatly influenced by outliers. This paper presents a new algorithm based on social triangle theory. Experiments show that the new algorithm is effective.

Persistent Interictal Musical Hallucination in a Patient With Mesial Temporal Sclerosis-Related Epilepsy: First Case Report and Etiopathological Hypothesis.

Science.gov (United States)

Borelli, Paolo; Vedovello, Marcella; Braga, Massimiliano; Pederzoli, Massimo; Beretta, Sandro

2016-12-01

Musical hallucination is a disorder of complex sound processing of instrumental music, songs, choirs, chants, etc. The underlying pathologies include moderate to severe acquired hearing loss (the auditory equivalent of Charles Bonnet syndrome), psychiatric illnesses (depression, schizophrenia), drug intoxication (benzodiazepines, salicylate, pentoxifylline, propranolol), traumatic lesions along the acoustic pathways, and epilepsy. The hallucinations are most likely to begin late in life; 70% of patients are women. Musical hallucination has no known specific therapy. Treating the underlying cause is the most effective approach; neuroleptic and antidepressant medications have only rarely succeeded.Musical hallucination in epilepsy typically presents as simple partial seizures originating in the lateral temporal cortex. To our knowledge, no formal report of musical hallucination in the interictal state has been published before. In contrast, other interictal psychotic features are a relatively common complication, especially in patients with long-standing drug-resistant epilepsy.We describe a 62-year-old woman with a long history of mesial temporal lobe epilepsy whose musical hallucination was solely interictal. We speculate on the possible link between temporal epilepsy and her hallucination. We hypothesize that, as a result of her epileptic activity-induced damage, an imbalance developed between the excitatory and inhibitory projections connecting the mesial temporal cortex to the other auditory structures. These structures may have generated hyperactivity in the lateral temporal cortex through a "release" mechanism that eventually resulted in musical hallucination.

Representing and querying now-relative relational medical data.

Science.gov (United States)

Anselma, Luca; Piovesan, Luca; Stantic, Bela; Terenziani, Paolo

2018-03-01

Temporal information plays a crucial role in medicine. Patients' clinical records are intrinsically temporal. Thus, in Medical Informatics there is an increasing need to store, support and query temporal data (particularly in relational databases), in order, for instance, to supplement decision-support systems. In this paper, we show that current approaches to relational data have remarkable limitations in the treatment of "now-relative" data (i.e., data holding true at the current time). This can severely compromise their applicability in general, and specifically in the medical context, where "now-relative" data are essential to assess the current status of the patients. We propose a theoretically grounded and application-independent relational approach to cope with now-relative data (which can be paired, e.g., with different decision support systems) overcoming such limitations. We propose a new temporal relational representation, which is the first relational model coping with the temporal indeterminacy intrinsic in now-relative data. We also propose new temporal algebraic operators to query them, supporting the distinction between possible and necessary time, and Allen's temporal relations between data. We exemplify the impact of our approach, and study the theoretical and computational properties of the new representation and algebra. Copyright © 2018 Elsevier B.V. All rights reserved.

Temporal discrimination, a cervical dystonia endophenotype: penetrance and functional correlates.

Science.gov (United States)

Kimmich, Okka; Molloy, Anna; Whelan, Robert; Williams, Laura; Bradley, David; Balsters, Joshua; Molloy, Fiona; Lynch, Tim; Healy, Daniel G; Walsh, Cathal; O'Riordan, Seán; Reilly, Richard B; Hutchinson, Michael

2014-05-01

The pathogenesis of adult-onset primary dystonia remains poorly understood. There is variable age-related and gender-related expression of the phenotype, the commonest of which is cervical dystonia. Endophenotypes may provide insight into underlying genetic and pathophysiological mechanisms of dystonia. The temporal discrimination threshold (TDT)-the shortest time interval at which two separate stimuli can be detected as being asynchronous-is abnormal both in patients with cervical dystonia and in their unaffected first-degree relatives. Functional magnetic resonance imaging (fMRI) studies have shown that putaminal activation positively correlates with the ease of temporal discrimination between two stimuli in healthy individuals. We hypothesized that abnormal temporal discrimination would exhibit similar age-related and gender-related penetrance as cervical dystonia and that unaffected relatives with an abnormal TDT would have reduced putaminal activation during a temporal discrimination task. TDTs were examined in a group of 192 healthy controls and in 158 unaffected first-degree relatives of 84 patients with cervical dystonia. In 24 unaffected first-degree relatives, fMRI scanning was performed during a temporal discrimination task. The prevalence of abnormal TDTs in unaffected female relatives reached 50% after age 48 years; whereas, in male relatives, penetrance of the endophenotype was reduced. By fMRI, relatives who had abnormal TDTs, compared with relatives who had normal TDTs, had significantly less activation in the putamina and in the middle frontal and precentral gyri. Only the degree of reduction of putaminal activity correlated significantly with worsening of temporal discrimination. These findings further support abnormal temporal discrimination as an endophenotype of cervical dystonia involving disordered basal ganglia circuits. © 2014 International Parkinson and Movement Disorder Society.

Price Discovery from Cross-Currency and FX Swaps: A Structural Analysis

OpenAIRE

Yasuaki Amatatsu; Naohiko Baba

2007-01-01

This paper investigates the relative role of price discovery between two long-term swap contracts that exchange between the U.S. dollar and the Japanese yen: cross-currency basis swap and FX (foreign exchange) swap. First, we show that these two swaps should be in a no-arbitrage relationship by allowing for differential risk premiums. Second, we empirically investigate the relative role of price discovery using the structural-form approach based on the state space models. Main finding are as ...

Selective Activation Around the Left Occipito-Temporal Sulcus for Words Relative to Pictures: Individual Variability or False Positives?

OpenAIRE

Wright, Nicholas D; Mechelli, Andrea; Noppeney, Uta; Veltman, Dick J; Rombouts, Serge ARB; Glensman, Janice; Haynes, John-Dylan; Price, Cathy J

2007-01-01

We used high-resolution fMRI to investigate claims that learning to read results in greater left occipito-temporal (OT) activation for written words relative to pictures of objects. In the first experiment, 9/16 subjects performing a one-back task showed activation in ?1 left OT voxel for words relative to pictures (P < 0.05 uncorrected). In a second experiment, another 9/15 subjects performing a semantic decision task activated ?1 left OT voxel for words relative to pictures. However, at thi...

Temporal bone trauma and imaging

International Nuclear Information System (INIS)

Turetschek, K.; Czerny, C.; Wunderbaldinger, P.; Steiner, E.

1997-01-01

Fractures of the temporal bone result from direct trauma to the temporal bone or occur as one component of a severe craniocerebral injury. Complications of temporal trauma are hemotympanon, facial nerve paralysis, conductive or sensorineur hearing loss, and leakage of cerebrospinal fluid. Erly recognition and an appropiate therapy may improve or prevent permanent deficits related to such complications. Only 20-30% of temporal bone fractures can be visualized by plain films. CT has displaced plain radiography in the investigation of the otological trauma because subtle bony details are best evaluated by CT which even can be reformatted in multiple projections, regardless of the original plane of scanning. Associated epidural, subdural, and intracerebral hemorrhagic lesions are better defined by MRI. (orig.) [de

A Tale of Two Discoveries: Comparing the Usability of Summon and EBSCO Discovery Service

Science.gov (United States)

Foster, Anita K.; MacDonald, Jean B.

2013-01-01

Web-scale discovery systems are gaining momentum among academic libraries as libraries seek a means to provide their users with a one-stop searching experience. Illinois State University's Milner Library found itself in the unique position of having access to two distinct discovery products, EBSCO Discovery Service and Serials Solutions' Summon.…

Temporal Preparation and Inhibitory Deficit in Fibromyalgia Syndrome

Science.gov (United States)

Correa, Angel; Miro, Elena; Martinez, M. Pilar; Sanchez, Ana I.; Lupianez, Juan

2011-01-01

Cognitive deficits in fibromyalgia may be specifically related to controlled processes, such as those measured by working memory or executive function tasks. This hypothesis was tested here by measuring controlled temporal preparation (temporal orienting) during a response inhibition (go no-go) task. Temporal orienting effects (faster reaction…

Usability Test Results for a Discovery Tool in an Academic Library

Directory of Open Access Journals (Sweden)

Jody Condit Fagan

2008-03-01

Full Text Available Discovery tools are emerging in libraries. These tools offer library patrons the ability to concurrently search the library catalog and journal articles. While vendors rush to provide feature-rich interfaces and access to as much content as possible, librarians wonder about the usefulness of these tools to library patrons. In order to learn about both the utility and usability of EBSCO Discovery Service, James Madison University conducted a usability test with eight students and two faculty members. The test consisted of nine tasks focused on common patron requests or related to the utility of specific discovery tool features. Software recorded participants’ actions and time on task, human observers judged the success of each task, and a post-survey questionnaire gathered qualitative feedback and comments from the participants.  Overall, participants were successful at most tasks, but specific usability problems suggested some interface changes for both EBSCO Discovery Service and JMU’s customizations of the tool.  The study also raised several questions for libraries above and beyond any specific discovery tool interface, including the scope and purpose of a discovery tool versus other library systems, working with the large result sets made possible by discovery tools, and navigation between the tool and other library services and resources.  This article will be of interest to those who are investigating discovery tools, selecting products, integrating discovery tools into a library web presence, or performing evaluations of similar systems.

47 CFR 65.105 - Discovery.

Science.gov (United States)

2010-10-01

... 47 Telecommunication 3 2010-10-01 2010-10-01 false Discovery. 65.105 Section 65.105... OF RETURN PRESCRIPTION PROCEDURES AND METHODOLOGIES Procedures § 65.105 Discovery. (a) Participants... evidence. (c) Discovery requests pursuant to § 65.105(b), including written interrogatories, shall be filed...

49 CFR 209.313 - Discovery.

Science.gov (United States)

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false Discovery. 209.313 Section 209.313 Transportation... TRANSPORTATION RAILROAD SAFETY ENFORCEMENT PROCEDURES Disqualification Procedures § 209.313 Discovery. (a... parties. Discovery is designed to enable a party to obtain relevant information needed for preparation of...

View discovery in OLAP databases through statistical combinatorial optimization

Energy Technology Data Exchange (ETDEWEB)

Hengartner, Nick W [Los Alamos National Laboratory; Burke, John [PNNL; Critchlow, Terence [PNNL; Joslyn, Cliff [PNNL; Hogan, Emilie [PNNL

2009-01-01

OnLine Analytical Processing (OLAP) is a relational database technology providing users with rapid access to summary, aggregated views of a single large database, and is widely recognized for knowledge representation and discovery in high-dimensional relational databases. OLAP technologies provide intuitive and graphical access to the massively complex set of possible summary views available in large relational (SQL) structured data repositories. The capability of OLAP database software systems to handle data complexity comes at a high price for analysts, presenting them a combinatorially vast space of views of a relational database. We respond to the need to deploy technologies sufficient to allow users to guide themselves to areas of local structure by casting the space of 'views' of an OLAP database as a combinatorial object of all projections and subsets, and 'view discovery' as an search process over that lattice. We equip the view lattice with statistical information theoretical measures sufficient to support a combinatorial optimization process. We outline 'hop-chaining' as a particular view discovery algorithm over this object, wherein users are guided across a permutation of the dimensions by searching for successive two-dimensional views, pushing seen dimensions into an increasingly large background filter in a 'spiraling' search process. We illustrate this work in the context of data cubes recording summary statistics for radiation portal monitors at US ports.

Paths of discovery: Comparing the search effectiveness of EBSCO Discovery Service, Summon, Google Scholar, and conventional library resources.

Directory of Open Access Journals (Sweden)

Müge Akbulut

2015-09-01

Full Text Available It is becoming hard for users to select significant sources among many others as number of scientific publications increase (Henning and Gunn, 2012. Search engines that are using cloud computing methods such as Google can list related documents successfully answering user requirements (Johnson, Levine and Smith, 2009. In order to meet users’ increasing demands, libraries started to use systems which enable users to access printed and electronic sources through a single interface. This study uses quantitative and qualitative methods to compare search effectiveness between Serial Solutions Summon, EBSCO Discovery Service (EDS web discovery tools, Google Scholar (GS and conventional library databases among users from Bucknell University and Illinois Wesleyan University.

Role of the medial temporal lobes in relational memory: Neuropsychological evidence from a cued recognition paradigm

OpenAIRE

Kan, Irene P.; Giovanello, Kelly S.; Schnyer, David M.; Makris, Nikos; Verfaellie, Mieke

2007-01-01

In this study, we examined the role of the hippocampus in relational memory by comparing item recognition performance in amnesic patients with medial temporal lobe (MTL) damage and their matched controls. Specifically, we investigated the contribution of associative memory to item recognition using a cued recognition paradigm. Control subjects studied cue-target pairs once, whereas amnesic patients studied cue-target pairs six times. Following study, subjects made recognition judgments about ...

Quantifying the Ease of Scientific Discovery.

Science.gov (United States)

Arbesman, Samuel

2011-02-01

It has long been known that scientific output proceeds on an exponential increase, or more properly, a logistic growth curve. The interplay between effort and discovery is clear, and the nature of the functional form has been thought to be due to many changes in the scientific process over time. Here I show a quantitative method for examining the ease of scientific progress, another necessary component in understanding scientific discovery. Using examples from three different scientific disciplines - mammalian species, chemical elements, and minor planets - I find the ease of discovery to conform to an exponential decay. In addition, I show how the pace of scientific discovery can be best understood as the outcome of both scientific output and ease of discovery. A quantitative study of the ease of scientific discovery in the aggregate, such as done here, has the potential to provide a great deal of insight into both the nature of future discoveries and the technical processes behind discoveries in science.

15 CFR 280.210 - Discovery.

Science.gov (United States)

2010-01-01

... 15 Commerce and Foreign Trade 1 2010-01-01 2010-01-01 false Discovery. 280.210 Section 280.210... STANDARDS AND TECHNOLOGY, DEPARTMENT OF COMMERCE ACCREDITATION AND ASSESSMENT PROGRAMS FASTENER QUALITY Enforcement § 280.210 Discovery. (a) General. The parties are encouraged to engage in voluntary discovery...

Estimating uncertainty and its temporal variation related to global climate models in quantifying climate change impacts on hydrology

Science.gov (United States)

Shen, Mingxi; Chen, Jie; Zhuan, Meijia; Chen, Hua; Xu, Chong-Yu; Xiong, Lihua

2018-01-01

Uncertainty estimation of climate change impacts on hydrology has received much attention in the research community. The choice of a global climate model (GCM) is usually considered as the largest contributor to the uncertainty of climate change impacts. The temporal variation of GCM uncertainty needs to be investigated for making long-term decisions to deal with climate change. Accordingly, this study investigated the temporal variation (mainly long-term) of uncertainty related to the choice of a GCM in predicting climate change impacts on hydrology by using multi-GCMs over multiple continuous future periods. Specifically, twenty CMIP5 GCMs under RCP4.5 and RCP8.5 emission scenarios were adapted to adequately represent this uncertainty envelope, fifty-one 30-year future periods moving from 2021 to 2100 with 1-year interval were produced to express the temporal variation. Future climatic and hydrological regimes over all future periods were compared to those in the reference period (1971-2000) using a set of metrics, including mean and extremes. The periodicity of climatic and hydrological changes and their uncertainty were analyzed using wavelet analysis, while the trend was analyzed using Mann-Kendall trend test and regression analysis. The results showed that both future climate change (precipitation and temperature) and hydrological response predicted by the twenty GCMs were highly uncertain, and the uncertainty increased significantly over time. For example, the change of mean annual precipitation increased from 1.4% in 2021-2050 to 6.5% in 2071-2100 for RCP4.5 in terms of the median value of multi-models, but the projected uncertainty reached 21.7% in 2021-2050 and 25.1% in 2071-2100 for RCP4.5. The uncertainty under a high emission scenario (RCP8.5) was much larger than that under a relatively low emission scenario (RCP4.5). Almost all climatic and hydrological regimes and their uncertainty did not show significant periodicity at the P = .05 significance

Augmenting Bag-of-Words: Data-Driven Discovery of Temporal and Structural Information for Activity Recognition

OpenAIRE

Bettadapura, Vinay; Schindler, Grant; Plotz, Thomaz; Essa, Irfan

2015-01-01

We present data-driven techniques to augment Bag of Words (BoW) models, which allow for more robust modeling and recognition of complex long-term activities, especially when the structure and topology of the activities are not known a priori. Our approach specifically addresses the limitations of standard BoW approaches, which fail to represent the underlying temporal and causal information that is inherent in activity streams. In addition, we also propose the use of randomly sampled regular ...

Auditory verbal hallucinations are related to cortical thinning in the left middle temporal gyrus of patients with schizophrenia.

Science.gov (United States)

Cui, Y; Liu, B; Song, M; Lipnicki, D M; Li, J; Xie, S; Chen, Y; Li, P; Lu, L; Lv, L; Wang, H; Yan, H; Yan, J; Zhang, H; Zhang, D; Jiang, T

2018-01-01

Auditory verbal hallucinations (AVHs) are one of the most common and severe symptoms of schizophrenia, but the neuroanatomical abnormalities underlying AVHs are not well understood. The present study aims to investigate whether AVHs are associated with cortical thinning. Participants were schizophrenia patients from four centers across China, 115 with AVHs and 93 without AVHs, as well as 261 healthy controls. All received 3 T T1-weighted brain scans, and whole brain vertex-wise cortical thickness was compared across groups. Correlations between AVH severity and cortical thickness were also determined. The left middle part of the middle temporal gyrus (MTG) was significantly thinner in schizophrenia patients with AVHs than in patients without AVHs and healthy controls. Inferences were made using a false discovery rate approach with a threshold at p < 0.05. Left MTG thickness did not differ between patients without AVHs and controls. These results were replicated by a meta-analysis showing them to be consistent across the four centers. Cortical thickness of the left MTG was also found to be inversely correlated with hallucination severity across all schizophrenia patients. The results of this multi-center study suggest that an abnormally thin left MTG could be involved in the pathogenesis of AVHs in schizophrenia.

The Relation of Learners' Motivation with the Process of Collaborative Scientific Discovery Learning

Science.gov (United States)

Saab, Nadira; van Joolingen, Wouter R.; van Hout-Wolters, B. H. A. M.

2009-01-01

In this study, we investigated the influence of individual learners' motivation on the collaborative discovery learning process. In this we distinguished the motivation of the individual learners and had eye for the composition of groups, which could be homogeneous or heterogeneous in terms of motivation. The study involved 73 dyads of 10th-grade…

Temporal phase relation of circadian neural oscillations as the basis ...

Indian Academy of Sciences (India)

MADHU

the day and the season of the year, it is not surprising that the temporal phase ..... germ cells, along with the formation of giant cells in some tubules. The spermatids ..... hourly intervals through the night to pinpoint more carefully the time of ...

10 CFR 1013.21 - Discovery.

Science.gov (United States)

2010-01-01

... 10 Energy 4 2010-01-01 2010-01-01 false Discovery. 1013.21 Section 1013.21 Energy DEPARTMENT OF ENERGY (GENERAL PROVISIONS) PROGRAM FRAUD CIVIL REMEDIES AND PROCEDURES § 1013.21 Discovery. (a) The following types of discovery are authorized: (1) Requests for production of documents for inspection and...

37 CFR 2.120 - Discovery.

Science.gov (United States)

2010-07-01

... 37 Patents, Trademarks, and Copyrights 1 2010-07-01 2010-07-01 false Discovery. 2.120 Section 2... COMMERCE RULES OF PRACTICE IN TRADEMARK CASES Procedure in Inter Partes Proceedings § 2.120 Discovery. (a... to disclosure and discovery shall apply in opposition, cancellation, interference and concurrent use...

46 CFR 550.502 - Discovery.

Science.gov (United States)

2010-10-01

... 46 Shipping 9 2010-10-01 2010-10-01 false Discovery. 550.502 Section 550.502 Shipping FEDERAL... Proceedings § 550.502 Discovery. The Commission may authorize a party to a proceeding to use depositions, written interrogatories, and discovery procedures that, to the extent practicable, are in conformity with...

15 CFR 785.8 - Discovery.

Science.gov (United States)

2010-01-01

... 15 Commerce and Foreign Trade 2 2010-01-01 2010-01-01 false Discovery. 785.8 Section 785.8... INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE ADDITIONAL PROTOCOL REGULATIONS ENFORCEMENT § 785.8 Discovery. (a) General. The parties are encouraged to engage in voluntary discovery regarding any matter, not...

45 CFR 96.65 - Discovery.

Science.gov (United States)

2010-10-01

... 45 Public Welfare 1 2010-10-01 2010-10-01 false Discovery. 96.65 Section 96.65 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION BLOCK GRANTS Hearing Procedure § 96.65 Discovery. The use of interrogatories, depositions, and other forms of discovery shall not be allowed. ...

49 CFR 31.21 - Discovery.

Science.gov (United States)

2010-10-01

... 49 Transportation 1 2010-10-01 2010-10-01 false Discovery. 31.21 Section 31.21 Transportation Office of the Secretary of Transportation PROGRAM FRAUD CIVIL REMEDIES § 31.21 Discovery. (a) The following types of discovery are authorized: (1) Requests for production of documents for inspection and...

43 CFR 4.1130 - Discovery methods.

Science.gov (United States)

2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Discovery methods. 4.1130 Section 4.1130... Special Rules Applicable to Surface Coal Mining Hearings and Appeals Discovery § 4.1130 Discovery methods. Parties may obtain discovery by one or more of the following methods— (a) Depositions upon oral...

Advances in fragment-based drug discovery platforms.

Science.gov (United States)

Orita, Masaya; Warizaya, Masaichi; Amano, Yasushi; Ohno, Kazuki; Niimi, Tatsuya

2009-11-01

Fragment-based drug discovery (FBDD) has been established as a powerful alternative and complement to traditional high-throughput screening techniques for identifying drug leads. At present, this technique is widely used among academic groups as well as small biotech and large pharmaceutical companies. In recent years, > 10 new compounds developed with FBDD have entered clinical development, and more and more attention in the drug discovery field is being focused on this technique. Under the FBDD approach, a fragment library of relatively small compounds (molecular mass = 100 - 300 Da) is screened by various methods and the identified fragment hits which normally weakly bind to the target are used as starting points to generate more potent drug leads. Because FBDD is still a relatively new drug discovery technology, further developments and optimizations in screening platforms and fragment exploitation can be expected. This review summarizes recent advances in FBDD platforms and discusses the factors important for the successful application of this technique. Under the FBDD approach, both identifying the starting fragment hit to be developed and generating the drug lead from that starting fragment hit are important. Integration of various techniques, such as computational technology, X-ray crystallography, NMR, surface plasmon resonance, isothermal titration calorimetry, mass spectrometry and high-concentration screening, must be applied in a situation-appropriate manner.

Spatio-temporal patterns of event-related potentials related to audiovisual synchrony judgments in older adults.

Science.gov (United States)

Chan, Yu Man; Pianta, Michael Julian; Bode, Stefan; McKendrick, Allison Maree

2017-07-01

Older adults have altered perception of the relative timing between auditory and visual stimuli, even when stimuli are scaled to equate detectability. To help understand why, this study investigated the neural correlates of audiovisual synchrony judgments in older adults using electroencephalography (EEG). Fourteen younger (18-32 year old) and 16 older (61-74 year old) adults performed an audiovisual synchrony judgment task on flash-pip stimuli while EEG was recorded. All participants were assessed to have healthy vision and hearing for their age. Observers responded to whether audiovisual pairs were perceived as synchronous or asynchronous via a button press. The results showed that the onset of predictive sensory information for synchrony judgments was not different between groups. Channels over auditory areas contributed more to this predictive sensory information than visual areas. The spatial-temporal profile of the EEG activity also indicates that older adults used different resources to maintain a similar level of performance in audiovisual synchrony judgments compared with younger adults. Copyright © 2017 Elsevier Inc. All rights reserved.

Chronic inflammation in refractory hippocampal sclerosis-related temporal lobe epilepsy.

Science.gov (United States)

Gales, Jordan M; Prayson, Richard A

2017-10-01

Emerging evidence suggests chronic inflammation may play a role in hippocampal sclerosis-associated temporal lobe epilepsy. We sought to systematically evaluate for its presence in a group of 315 patients who underwent surgery for medically-refractory epilepsy and who had hippocampal sclerosis. Upon histologic review of hematoxylin and eosin stained tissue sections, 95 (41%) cases demonstrated the presence of lymphocytes within the perivascular region and diffusely within the brain parenchyma. Those cases with chronic inflammation evident on hematoxylin and eosin staining were significantly more likely to experience a post-operative seizure recurrence than those without it (p=0.03). In 9 cases of hippocampi with chronic inflammation observed on hematoxylin and eosin stained sections, there was a mixture of both T (CD3+) and B (CD20+) lymphocytes located around blood vessels and interspersed within the brain parenchyma and a predominance of CD4 positive T cells versus CD8 positive cells. Ten hippocampi, apparently devoid of chronic inflammation upon inspection with hematoxylin and eosin stained sections, were stained with the lymphocyte common antigen CD45. In all 10 cases, scattered lymphoid cells were observed in the brain parenchyma, suggesting some level of chronic inflammation may be present in more cases than casual inspection might suggest. This study was the first to evaluate the incidence of chronic inflammation within a large temporal lobe epilepsy population. The study findings suggest chronic inflammation may be a more common component of hippocampal sclerosis -associated temporal lobe epilepsy than previously believed. Copyright © 2017 Elsevier Inc. All rights reserved.

6 CFR 13.21 - Discovery.

Science.gov (United States)

2010-01-01

... 6 Domestic Security 1 2010-01-01 2010-01-01 false Discovery. 13.21 Section 13.21 Domestic Security DEPARTMENT OF HOMELAND SECURITY, OFFICE OF THE SECRETARY PROGRAM FRAUD CIVIL REMEDIES § 13.21 Discovery. (a) In general. (1) The following types of discovery are authorized: (i) Requests for production of...

45 CFR 99.23 - Discovery.

Science.gov (United States)

2010-10-01

... 45 Public Welfare 1 2010-10-01 2010-10-01 false Discovery. 99.23 Section 99.23 Public Welfare... DEVELOPMENT FUND Hearing Procedures § 99.23 Discovery. The Department, the Lead Agency, and any individuals or groups recognized as parties shall have the right to conduct discovery (including depositions) against...

20 CFR 355.21 - Discovery.

Science.gov (United States)

2010-04-01

... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Discovery. 355.21 Section 355.21 Employees... UNDER THE PROGRAM FRAUD CIVIL REMEDIES ACT OF 1986 § 355.21 Discovery. (a) The following types of discovery are authorized: (1) Requests for production of documents for inspection and copying; (2) Requests...

10 CFR 2.1018 - Discovery.

Science.gov (United States)

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false Discovery. 2.1018 Section 2.1018 Energy NUCLEAR REGULATORY... Geologic Repository § 2.1018 Discovery. (a)(1) Parties, potential parties, and interested governmental participants in the high-level waste licensing proceeding may obtain discovery by one or more of the following...

28 CFR 71.21 - Discovery.

Science.gov (United States)

2010-07-01

... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Discovery. 71.21 Section 71.21 Judicial... REMEDIES ACT OF 1986 Implementation for Actions Initiated by the Department of Justice § 71.21 Discovery. (a) The following types of discovery are authorized: (1) Requests for production of documents for...

13 CFR 134.310 - Discovery.

Science.gov (United States)

2010-01-01

... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Discovery. 134.310 Section 134.310 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION RULES OF PROCEDURE GOVERNING CASES BEFORE THE... Designations § 134.310 Discovery. Discovery will not be permitted in appeals from size determinations or NAICS...

34 CFR 33.21 - Discovery.

Science.gov (United States)

2010-07-01

... 34 Education 1 2010-07-01 2010-07-01 false Discovery. 33.21 Section 33.21 Education Office of the Secretary, Department of Education PROGRAM FRAUD CIVIL REMEDIES ACT § 33.21 Discovery. (a) The following types of discovery are authorized: (1) Requests for production of documents for inspection and copying...

28 CFR 18.7 - Discovery.

Science.gov (United States)

2010-07-01

... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Discovery. 18.7 Section 18.7 Judicial Administration DEPARTMENT OF JUSTICE OFFICE OF JUSTICE PROGRAMS HEARING AND APPEAL PROCEDURES § 18.7 Discovery.... Such order may be entered upon a showing that the deposition is necessary for discovery purposes, and...

7 CFR 1.322 - Discovery.

Science.gov (United States)

2010-01-01

... 7 Agriculture 1 2010-01-01 2010-01-01 false Discovery. 1.322 Section 1.322 Agriculture Office of... Under the Program Fraud Civil Remedies Act of 1986 § 1.322 Discovery. (a) The following types of discovery are authorized: (1) Requests for production, inspection and photocopying of documents; (2...

45 CFR 1386.103 - Discovery.

Science.gov (United States)

2010-10-01

... 45 Public Welfare 4 2010-10-01 2010-10-01 false Discovery. 1386.103 Section 1386.103 Public... Hearing Procedures § 1386.103 Discovery. The Department and any party named in the Notice issued pursuant to § 1386.90 has the right to conduct discovery (including depositions) against opposing parties as...

45 CFR 79.21 - Discovery.

Science.gov (United States)

2010-10-01

... 45 Public Welfare 1 2010-10-01 2010-10-01 false Discovery. 79.21 Section 79.21 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION PROGRAM FRAUD CIVIL REMEDIES § 79.21 Discovery. (a) The following types of discovery are authorized: (1) Requests for production of documents for...

12 CFR 308.520 - Discovery.

Science.gov (United States)

2010-01-01

... 12 Banks and Banking 4 2010-01-01 2010-01-01 false Discovery. 308.520 Section 308.520 Banks and... PROCEDURE Program Fraud Civil Remedies and Procedures § 308.520 Discovery. (a) The following types of discovery are authorized: (1) Requests for production of documents for inspection and copying; (2) Requests...

47 CFR 1.729 - Discovery.

Science.gov (United States)

2010-10-01

... 47 Telecommunication 1 2010-10-01 2010-10-01 false Discovery. 1.729 Section 1.729..., and Reports Involving Common Carriers Formal Complaints § 1.729 Discovery. (a) Subject to paragraph (i... seek discovery of any non-privileged matter that is relevant to the material facts in dispute in the...

7 CFR 283.12 - Discovery.

Science.gov (United States)

2010-01-01

... 7 Agriculture 4 2010-01-01 2010-01-01 false Discovery. 283.12 Section 283.12 Agriculture... of $50,000 or More § 283.12 Discovery. (a) Dispositions—(1) Motion for taking deposition. Only upon a... exist if the information sought appears reasonably calculated to lead to the discovery of admissible...

Cell and small animal models for phenotypic drug discovery

Directory of Open Access Journals (Sweden)

Szabo M

2017-06-01

Full Text Available Mihaly Szabo,1 Sara Svensson Akusjärvi,1 Ankur Saxena,1 Jianping Liu,2 Gayathri Chandrasekar,1 Satish S Kitambi1 1Department of Microbiology Tumor, and Cell Biology, 2Department of Biochemistry and Biophysics, Karolinska Institutet, Solna, Sweden Abstract: The phenotype-based drug discovery (PDD approach is re-emerging as an alternative platform for drug discovery. This review provides an overview of the various model systems and technical advances in imaging and image analyses that strengthen the PDD platform. In PDD screens, compounds of therapeutic value are identified based on the phenotypic perturbations produced irrespective of target(s or mechanism of action. In this article, examples of phenotypic changes that can be detected and quantified with relative ease in a cell-based setup are discussed. In addition, a higher order of PDD screening setup using small animal models is also explored. As PDD screens integrate physiology and multiple signaling mechanisms during the screening process, the identified hits have higher biomedical applicability. Taken together, this review highlights the advantages gained by adopting a PDD approach in drug discovery. Such a PDD platform can complement target-based systems that are currently in practice to accelerate drug discovery. Keywords: phenotype, screening, PDD, discovery, zebrafish, drug

Selective activation around the left occipito-temporal sulcus for words relative to pictures: Individual variability or false positives?

NARCIS (Netherlands)

Wright, Nicholas D.; Mechelli, Andrea; Noppeney, Uta; Veltman, Dick J.; Rombouts, Serge A. R. B.; Glensman, Janice; Haynes, John-Dylan; Price, Cathy J.

2008-01-01

We used high-resolution fMRI to investigate claims that learning to read r !sults in greater left occipito-temporal (OT) activation for written words relative to pictures of objects. In tl e first experiment, 9/16 subjects performing a one-back task showed activation in >= 1 left OT voxel for word:

42 CFR 1005.7 - Discovery.

Science.gov (United States)

2010-10-01

... 42 Public Health 5 2010-10-01 2010-10-01 false Discovery. 1005.7 Section 1005.7 Public Health... OF EXCLUSIONS, CIVIL MONEY PENALTIES AND ASSESSMENTS § 1005.7 Discovery. (a) A party may make a... and any forms of discovery, other than those permitted under paragraph (a) of this section, are not...

29 CFR 1603.210 - Discovery.

Science.gov (United States)

2010-07-01

... 29 Labor 4 2010-07-01 2010-07-01 false Discovery. 1603.210 Section 1603.210 Labor Regulations... GOVERNMENT EMPLOYEE RIGHTS ACT OF 1991 Hearings § 1603.210 Discovery. (a) Unless otherwise ordered by the administrative law judge, discovery may begin as soon as the complaint has been transmitted to the administrative...

45 CFR 150.435 - Discovery.

Science.gov (United States)

2010-10-01

... 45 Public Welfare 1 2010-10-01 2010-10-01 false Discovery. 150.435 Section 150.435 Public Welfare... AND INDIVIDUAL INSURANCE MARKETS Administrative Hearings § 150.435 Discovery. (a) The parties must identify any need for discovery from the opposing party as soon as possible, but no later than the time for...

34 CFR 81.16 - Discovery.

Science.gov (United States)

2010-07-01

... 34 Education 1 2010-07-01 2010-07-01 false Discovery. 81.16 Section 81.16 Education Office of the... Discovery. (a) The parties to a case are encouraged to exchange relevant documents and information voluntarily. (b) The ALJ, at a party's request, may order compulsory discovery described in paragraph (c) of...

29 CFR 1905.25 - Discovery.

Science.gov (United States)

2010-07-01

... 29 Labor 5 2010-07-01 2010-07-01 false Discovery. 1905.25 Section 1905.25 Labor Regulations... OCCUPATIONAL SAFETY AND HEALTH ACT OF 1970 Hearings § 1905.25 Discovery. (a) Depositions. (1) For reasons of... discovery. Whenever appropriate to a just disposition of any issue in a hearing, the presiding hearing...

12 CFR 1780.26 - Discovery.

Science.gov (United States)

2010-01-01

... 12 Banks and Banking 7 2010-01-01 2010-01-01 false Discovery. 1780.26 Section 1780.26 Banks and... OF PRACTICE AND PROCEDURE RULES OF PRACTICE AND PROCEDURE Prehearing Proceedings § 1780.26 Discovery. (a) Limits on discovery. Subject to the limitations set out in paragraphs (b), (d), and (e) of this...

45 CFR 160.516 - Discovery.

Science.gov (United States)

2010-10-01

... 45 Public Welfare 1 2010-10-01 2010-10-01 false Discovery. 160.516 Section 160.516 Public Welfare... ADMINISTRATIVE REQUIREMENTS Procedures for Hearings § 160.516 Discovery. (a) A party may make a request to... forms of discovery, other than those permitted under paragraph (a) of this section, are not authorized...

42 CFR 430.86 - Discovery.

Science.gov (United States)

2010-10-01

... 42 Public Health 4 2010-10-01 2010-10-01 false Discovery. 430.86 Section 430.86 Public Health... Plans and Practice to Federal Requirements § 430.86 Discovery. CMS and any party named in the notice issued under § 430.70 has the right to conduct discovery (including depositions) against opposing parties...

Two-sorted Point-Interval Temporal Logics

DEFF Research Database (Denmark)

Balbiani, Philippe; Goranko, Valentin; Sciavicco, Guido

2011-01-01

There are two natural and well-studied approaches to temporal ontology and reasoning: point-based and interval-based. Usually, interval-based temporal reasoning deals with points as particular, duration-less intervals. Here we develop explicitly two-sorted point-interval temporal logical framework...... whereby time instants (points) and time periods (intervals) are considered on a par, and the perspective can shift between them within the formal discourse. We focus on fragments involving only modal operators that correspond to the inter-sort relations between points and intervals. We analyze...

Discovery Driven Growth

DEFF Research Database (Denmark)

Bukh, Per Nikolaj

2009-01-01

Anmeldelse af Discovery Driven Growh : A breakthrough process to reduce risk and seize opportunity, af Rita G. McGrath & Ian C. MacMillan, Boston: Harvard Business Press. Udgivelsesdato: 14 august......Anmeldelse af Discovery Driven Growh : A breakthrough process to reduce risk and seize opportunity, af Rita G. McGrath & Ian C. MacMillan, Boston: Harvard Business Press. Udgivelsesdato: 14 august...

42 CFR 405.1037 - Discovery.

Science.gov (United States)

2010-10-01

... 42 Public Health 2 2010-10-01 2010-10-01 false Discovery. 405.1037 Section 405.1037 Public Health... Appeals Under Original Medicare (Part A and Part B) Alj Hearings § 405.1037 Discovery. (a) General rules. (1) Discovery is permissible only when CMS or its contractor elects to participate in an ALJ hearing...

20 CFR 498.207 - Discovery.

Science.gov (United States)

2010-04-01

... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Discovery. 498.207 Section 498.207 Employees... § 498.207 Discovery. (a) For the purpose of inspection and copying, a party may make a request to...) Any form of discovery other than that permitted under paragraph (a) of this section, such as requests...

42 CFR 93.512 - Discovery.

Science.gov (United States)

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Discovery. 93.512 Section 93.512 Public Health... Process § 93.512 Discovery. (a) Request to provide documents. A party may only request another party to...) Responses to a discovery request. Within 30 days of receiving a request for the production of documents, a...

42 CFR 3.516 - Discovery.

Science.gov (United States)

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Discovery. 3.516 Section 3.516 Public Health PUBLIC... AND PATIENT SAFETY WORK PRODUCT Enforcement Program § 3.516 Discovery. (a) A party may make a request... and any forms of discovery, other than those permitted under paragraph (a) of this section, are not...

29 CFR 22.21 - Discovery.

Science.gov (United States)

2010-07-01

... 29 Labor 1 2010-07-01 2010-07-01 true Discovery. 22.21 Section 22.21 Labor Office of the Secretary of Labor PROGRAM FRAUD CIVIL REMEDIES ACT OF 1986 § 22.21 Discovery. (a) The following types of discovery are authorized: (1) Requests for production of documents for inspection and copying; (2) Requests...

Computational methods in drug discovery

Directory of Open Access Journals (Sweden)

Sumudu P. Leelananda

2016-12-01

Full Text Available The process for drug discovery and development is challenging, time consuming and expensive. Computer-aided drug discovery (CADD tools can act as a virtual shortcut, assisting in the expedition of this long process and potentially reducing the cost of research and development. Today CADD has become an effective and indispensable tool in therapeutic development. The human genome project has made available a substantial amount of sequence data that can be used in various drug discovery projects. Additionally, increasing knowledge of biological structures, as well as increasing computer power have made it possible to use computational methods effectively in various phases of the drug discovery and development pipeline. The importance of in silico tools is greater than ever before and has advanced pharmaceutical research. Here we present an overview of computational methods used in different facets of drug discovery and highlight some of the recent successes. In this review, both structure-based and ligand-based drug discovery methods are discussed. Advances in virtual high-throughput screening, protein structure prediction methods, protein–ligand docking, pharmacophore modeling and QSAR techniques are reviewed.

Spatio-Temporal Data Exchange Standards

DEFF Research Database (Denmark)

Jensen, Christian Søndergaard; Schmidt, Albrecht

2003-01-01

We believe that research that concerns aspects of spatio-temporal data management may benefit from taking into account the various standards for spatio-temporal data formats. For example, this may contribute to rendering prototype software “open” and more readily useful. This paper thus identifies...... and briefly surveys standardization in relation to primarily the exchange and integration of spatio-temporal data. An overview of several data exchange languages is offered, along with reviews their potential for facilitating the collection of test data and the leveraging of prototypes. The standards, most...... of which are XML-based, lend themselves to the integration of prototypes into middleware architectures, e.g., as Web services....

A Temporal Mining Framework for Classifying Un-Evenly Spaced Clinical Data: An Approach for Building Effective Clinical Decision-Making System.

Science.gov (United States)

Jane, Nancy Yesudhas; Nehemiah, Khanna Harichandran; Arputharaj, Kannan

2016-01-01

Clinical time-series data acquired from electronic health records (EHR) are liable to temporal complexities such as irregular observations, missing values and time constrained attributes that make the knowledge discovery process challenging. This paper presents a temporal rough set induced neuro-fuzzy (TRiNF) mining framework that handles these complexities and builds an effective clinical decision-making system. TRiNF provides two functionalities namely temporal data acquisition (TDA) and temporal classification. In TDA, a time-series forecasting model is constructed by adopting an improved double exponential smoothing method. The forecasting model is used in missing value imputation and temporal pattern extraction. The relevant attributes are selected using a temporal pattern based rough set approach. In temporal classification, a classification model is built with the selected attributes using a temporal pattern induced neuro-fuzzy classifier. For experimentation, this work uses two clinical time series dataset of hepatitis and thrombosis patients. The experimental result shows that with the proposed TRiNF framework, there is a significant reduction in the error rate, thereby obtaining the classification accuracy on an average of 92.59% for hepatitis and 91.69% for thrombosis dataset. The obtained classification results prove the efficiency of the proposed framework in terms of its improved classification accuracy.

10 CFR 205.198 - Discovery.

Science.gov (United States)

2010-01-01

... 10 Energy 3 2010-01-01 2010-01-01 false Discovery. 205.198 Section 205.198 Energy DEPARTMENT OF... of Proposed Disallowance, and Order of Disallowance § 205.198 Discovery. (a) If a person intends to file a Motion for Discovery, he must file it at the same time that he files his Statement of Objections...

12 CFR 908.46 - Discovery.

Science.gov (United States)

2010-01-01

... 12 Banks and Banking 7 2010-01-01 2010-01-01 false Discovery. 908.46 Section 908.46 Banks and... PRACTICE AND PROCEDURE IN HEARINGS ON THE RECORD Pre-Hearing Proceedings § 908.46 Discovery. (a) Limits on discovery. Subject to the limitations set out in paragraphs (b), (d), and (e) of this section, any party to...

21 CFR 17.23 - Discovery.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Discovery. 17.23 Section 17.23 Food and Drugs FOOD... HEARINGS § 17.23 Discovery. (a) No later than 60 days prior to the hearing, unless otherwise ordered by the..., depositions, and any forms of discovery, other than those permitted under paragraphs (a) and (e) of this...

45 CFR 2554.26 - Are there limits on disclosure of documents or discovery?

Science.gov (United States)

2010-10-01

... discovery? 2554.26 Section 2554.26 Public Welfare Regulations Relating to Public Welfare (Continued) CORPORATION FOR NATIONAL AND COMMUNITY SERVICE PROGRAM FRAUD CIVIL REMEDIES ACT REGULATIONS Hearing Provisions § 2554.26 Are there limits on disclosure of documents or discovery? (a) Upon written request to the...

Mass Spectrometry–Based Biomarker Discovery: Toward a Global Proteome Index of Individuality

Science.gov (United States)

Hawkridge, Adam M.; Muddiman, David C.

2011-01-01

Biomarker discovery and proteomics have become synonymous with mass spectrometry in recent years. Although this conflation is an injustice to the many essential biomolecular techniques widely used in biomarker-discovery platforms, it underscores the power and potential of contemporary mass spectrometry. Numerous novel and powerful technologies have been developed around mass spectrometry, proteomics, and biomarker discovery over the past 20 years to globally study complex proteomes (e.g., plasma). However, very few large-scale longitudinal studies have been carried out using these platforms to establish the analytical variability relative to true biological variability. The purpose of this review is not to cover exhaustively the applications of mass spectrometry to biomarker discovery, but rather to discuss the analytical methods and strategies that have been developed for mass spectrometry–based biomarker-discovery platforms and to place them in the context of the many challenges and opportunities yet to be addressed. PMID:20636062

Cortical Correlates of Binaural Temporal Processing Deficits in Older Adults.

Science.gov (United States)

Eddins, Ann Clock; Eddins, David A

This study was designed to evaluate binaural temporal processing in young and older adults using a binaural masking level difference (BMLD) paradigm. Using behavioral and electrophysiological measures within the same listeners, a series of stimulus manipulations was used to evaluate the relative contribution of binaural temporal fine-structure and temporal envelope cues. We evaluated the hypotheses that age-related declines in the BMLD task would be more strongly associated with temporal fine-structure than envelope cues and that age-related declines in behavioral measures would be correlated with cortical auditory evoked potential (CAEP) measures. Thirty adults participated in the study, including 10 young normal-hearing, 10 older normal-hearing, and 10 older hearing-impaired adults with bilaterally symmetric, mild-to-moderate sensorineural hearing loss. Behavioral and CAEP thresholds were measured for diotic (So) and dichotic (Sπ) tonal signals presented in continuous diotic (No) narrowband noise (50-Hz wide) maskers. Temporal envelope cues were manipulated by using two different narrowband maskers; Gaussian noise (GN) with robust envelope fluctuations and low-noise noise (LNN) with minimal envelope fluctuations. The potential to use temporal fine-structure cues was controlled by varying the signal frequency (500 or 4000 Hz), thereby relying on the natural decline in phase-locking with increasing frequency. Behavioral and CAEP thresholds were similar across groups for diotic conditions, while the masking release in dichotic conditions was larger for younger than for older participants. Across all participants, BMLDs were larger for GN than LNN and for 500-Hz than for 4000-Hz conditions, where envelope and fine-structure cues were most salient, respectively. Specific age-related differences were demonstrated for 500-Hz dichotic conditions in GN and LNN, reflecting reduced binaural temporal fine-structure coding. No significant age effects were observed for 4000

Event-related potentials reflect impaired temporal interval learning following haloperidol administration.

Science.gov (United States)

Forster, Sarah E; Zirnheld, Patrick; Shekhar, Anantha; Steinhauer, Stuart R; O'Donnell, Brian F; Hetrick, William P

2017-09-01

Signals carried by the mesencephalic dopamine system and conveyed to anterior cingulate cortex are critically implicated in probabilistic reward learning and performance monitoring. A common evaluative mechanism purportedly subserves both functions, giving rise to homologous medial frontal negativities in feedback- and response-locked event-related brain potentials (the feedback-related negativity (FRN) and the error-related negativity (ERN), respectively), reflecting dopamine-dependent prediction error signals to unexpectedly negative events. Consistent with this model, the dopamine receptor antagonist, haloperidol, attenuates the ERN, but effects on FRN have not yet been evaluated. ERN and FRN were recorded during a temporal interval learning task (TILT) following randomized, double-blind administration of haloperidol (3 mg; n = 18), diphenhydramine (an active control for haloperidol; 25 mg; n = 20), or placebo (n = 21) to healthy controls. Centroparietal positivities, the Pe and feedback-locked P300, were also measured and correlations between ERP measures and behavioral indices of learning, overall accuracy, and post-error compensatory behavior were evaluated. We hypothesized that haloperidol would reduce ERN and FRN, but that ERN would uniquely track automatic, error-related performance adjustments, while FRN would be associated with learning and overall accuracy. As predicted, ERN was reduced by haloperidol and in those exhibiting less adaptive post-error performance; however, these effects were limited to ERNs following fast timing errors. In contrast, the FRN was not affected by drug condition, although increased FRN amplitude was associated with improved accuracy. Significant drug effects on centroparietal positivities were also absent. Our results support a functional and neurobiological dissociation between the ERN and FRN.

NASA Reverb: Standards-Driven Earth Science Data and Service Discovery

Science.gov (United States)

Cechini, M. F.; Mitchell, A.; Pilone, D.

2011-12-01

NASA's Earth Observing System Data and Information System (EOSDIS) is a core capability in NASA's Earth Science Data Systems Program. NASA's EOS ClearingHOuse (ECHO) is a metadata catalog for the EOSDIS, providing a centralized catalog of data products and registry of related data services. Working closely with the EOSDIS community, the ECHO team identified a need to develop the next generation EOS data and service discovery tool. This development effort relied on the following principles: + Metadata Driven User Interface - Users should be presented with data and service discovery capabilities based on dynamic processing of metadata describing the targeted data. + Integrated Data & Service Discovery - Users should be able to discovery data and associated data services that facilitate their research objectives. + Leverage Common Standards - Users should be able to discover and invoke services that utilize common interface standards. Metadata plays a vital role facilitating data discovery and access. As data providers enhance their metadata, more advanced search capabilities become available enriching a user's search experience. Maturing metadata formats such as ISO 19115 provide the necessary depth of metadata that facilitates advanced data discovery capabilities. Data discovery and access is not limited to simply the retrieval of data granules, but is growing into the more complex discovery of data services. These services include, but are not limited to, services facilitating additional data discovery, subsetting, reformatting, and re-projecting. The discovery and invocation of these data services is made significantly simpler through the use of consistent and interoperable standards. By utilizing an adopted standard, developing standard-specific adapters can be utilized to communicate with multiple services implementing a specific protocol. The emergence of metadata standards such as ISO 19119 plays a similarly important role in discovery as the 19115 standard

The circumstances of minor planet discovery

International Nuclear Information System (INIS)

Pilcher, F.

1989-01-01

The circumstances of discoveries of minor planets are presented in tabular form. Complete data are given for planets 2125-4044, together with notes pertaining to these planets. Information in the table includes the permanent number; the official name; for planets 330 and forward, the table includes the provisional designation attached to the discovery apparition and the year, month, the day of discovery, and the discovery place

Node Discovery and Interpretation in Unstructured Resource-Constrained Environments

DEFF Research Database (Denmark)

Gechev, Miroslav; Kasabova, Slavyana; Mihovska, Albena D.

2014-01-01

for the discovery, linking and interpretation of nodes in unstructured and resource-constrained network environments and their interrelated and collective use for the delivery of smart services. The model is based on a basic mathematical approach, which describes and predicts the success of human interactions...... in the context of long-term relationships and identifies several key variables in the context of communications in resource-constrained environments. The general theoretical model is described and several algorithms are proposed as part of the node discovery, identification, and linking processes in relation...

Early detection surveillance for an emerging plant pathogen: a rule of thumb to predict prevalence at first discovery.

Science.gov (United States)

Parnell, S; Gottwald, T R; Cunniffe, N J; Alonso Chavez, V; van den Bosch, F

2015-09-07

Emerging plant pathogens are a significant problem for conservation and food security. Surveillance is often instigated in an attempt to detect an invading epidemic before it gets out of control. Yet in practice many epidemics are not discovered until already at a high prevalence, partly due to a lack of quantitative understanding of how surveillance effort and the dynamics of an invading epidemic relate. We test a simple rule of thumb to determine, for a surveillance programme taking a fixed number of samples at regular intervals, the distribution of the prevalence an epidemic will have reached on first discovery (discovery-prevalence) and its expectation E(q*). We show that E(q*) = r/(N/Δ), i.e. simply the rate of epidemic growth divided by the rate of sampling; where r is the epidemic growth rate, N is the sample size and Δ is the time between sampling rounds. We demonstrate the robustness of this rule of thumb using spatio-temporal epidemic models as well as data from real epidemics. Our work supports the view that, for the purposes of early detection surveillance, simple models can provide useful insights in apparently complex systems. The insight can inform decisions on surveillance resource allocation in plant health and has potential applicability to invasive species generally. © 2015 The Author(s).

Toxins and drug discovery.

Science.gov (United States)

Harvey, Alan L

2014-12-15

Components from venoms have stimulated many drug discovery projects, with some notable successes. These are briefly reviewed, from captopril to ziconotide. However, there have been many more disappointments on the road from toxin discovery to approval of a new medicine. Drug discovery and development is an inherently risky business, and the main causes of failure during development programmes are outlined in order to highlight steps that might be taken to increase the chances of success with toxin-based drug discovery. These include having a clear focus on unmet therapeutic needs, concentrating on targets that are well-validated in terms of their relevance to the disease in question, making use of phenotypic screening rather than molecular-based assays, and working with development partners with the resources required for the long and expensive development process. Copyright © 2014 The Author. Published by Elsevier Ltd.. All rights reserved.

mHealth Visual Discovery Dashboard.

Science.gov (United States)

Fang, Dezhi; Hohman, Fred; Polack, Peter; Sarker, Hillol; Kahng, Minsuk; Sharmin, Moushumi; al'Absi, Mustafa; Chau, Duen Horng

2017-09-01

We present Discovery Dashboard, a visual analytics system for exploring large volumes of time series data from mobile medical field studies. Discovery Dashboard offers interactive exploration tools and a data mining motif discovery algorithm to help researchers formulate hypotheses, discover trends and patterns, and ultimately gain a deeper understanding of their data. Discovery Dashboard emphasizes user freedom and flexibility during the data exploration process and enables researchers to do things previously challenging or impossible to do - in the web-browser and in real time. We demonstrate our system visualizing data from a mobile sensor study conducted at the University of Minnesota that included 52 participants who were trying to quit smoking.

Neuroproteomics and Systems Biology Approach to Identify Temporal Biomarker Changes Post Experimental Traumatic Brain Injury in Rats

Directory of Open Access Journals (Sweden)

Firas H Kobeissy

2016-11-01

Full Text Available Traumatic brain injury (TBI represents a critical health problem of which diagnosis, management and treatment remain challenging. TBI is a contributing factor in approximately 1/3 of all injury-related deaths in the United States. The Centers for Disease Control and Prevention (CDC estimate that 1.7 million TBI people suffer a TBI in the United States annually. Efforts continue to focus on elucidating the complex molecular mechanisms underlying TBI pathophysiology and defining sensitive and specific biomarkers that can aid in improving patient management and care. Recently, the area of neuroproteomics-systems biology is proving to be a prominent tool in biomarker discovery for central nervous system (CNS injury and other neurological diseases. In this work, we employed the controlled cortical impact (CCI model of experimental TBI in rat model to assess the temporal-global proteome changes after acute (1 day and for the first time, subacute (7 days, post-injury time frame using the established CAX-PAGE LC-MS/MS platform for protein separation combined with discrete systems biology analyses to identify temporal biomarker changes related to this rat TBI model. Rather than focusing on any one individual molecular entities, we used in silico systems biology approach to understand the global dynamics that govern proteins that are differentially altered post-injury. In addition, gene ontology analysis of the proteomic data was conducted in order to categorize the proteins by molecular function, biological process, and cellular localization. Results show alterations in several proteins related to inflammatory responses and oxidative stress in both acute (1 day and subacute (7 days periods post TBI. Moreover, results suggest a differential upregulation of neuroprotective proteins at 7-days post-CCI involved in cellular functions such as neurite growth, regeneration, and axonal guidance. Our study is amongst the first to assess temporal neuroproteome

Service discovery at home

NARCIS (Netherlands)

Sundramoorthy, V.; Scholten, Johan; Jansen, P.G.; Hartel, Pieter H.

2003-01-01

Service discovery is a fairly new field that kicked off since the advent of ubiquitous computing and has been found essential in the making of intelligent networks by implementing automated discovery and remote control between devices. This paper provides an overview and comparison of several

Ictal affective symptoms in temporal lobe epilepsy are related to gender and age.

Science.gov (United States)

Toth, Vanda; Fogarasi, Andras; Karadi, Kazmer; Kovacs, Norbert; Ebner, Alois; Janszky, Jozsef

2010-07-01

We systematically analyzed the video-recorded and patient-reported, as well as positive and negative ictal affective symptoms (IAS) in temporal lobe epilepsy (TLE). Our aim was to assess (1) frequency, (2) gender effect, (3) lateralizing significance, (4) localizing value, and (5) prognostic significance in epilepsy surgery of IAS in patients with video-registered seizures. We reviewed ictal video recordings of 184 patients (99 women, aged 16-63). All patients had surgery for intractable TLE with video-recorded complex partial seizures (CPS) due to temporal lobe lesions visualized by high-resolution magnetic resonance imaging (MRI). Affective auras (AAs) were categorized into two groups: positive or negative. We registered AAs in 18% of patients: positive in 3%, negative in 15%. We saw ictal affective behavior (IAB) in 22% of patients; 10% had positive, whereas 14% had negative IAB. Two patients had both positive and negative IAB. AAs showed an association with IAB in case of fear expression versus fear auras (p = 0.018). IAB, especially negative IAB, occurred more often in women than in men. Patients with negative IAB were younger than others. We could not demonstrate an association between IAS and the localization, lateralization, or hemispheric dominance. Surgical outcome did not associate with IAS. Patient-reported and video-recorded negative-but not positive-affective signs are related to each other. Video-recorded negative AAs occur more often in women and young patients.

The Greatest Mathematical Discovery?

Energy Technology Data Exchange (ETDEWEB)

Bailey, David H.; Borwein, Jonathan M.

2010-05-12

What mathematical discovery more than 1500 years ago: (1) Is one of the greatest, if not the greatest, single discovery in the field of mathematics? (2) Involved three subtle ideas that eluded the greatest minds of antiquity, even geniuses such as Archimedes? (3) Was fiercely resisted in Europe for hundreds of years after its discovery? (4) Even today, in historical treatments of mathematics, is often dismissed with scant mention, or else is ascribed to the wrong source? Answer: Our modern system of positional decimal notation with zero, together with the basic arithmetic computational schemes, which were discovered in India about 500 CE.

Open Drug Discovery Toolkit (ODDT): a new open-source player in the drug discovery field.

Science.gov (United States)

Wójcikowski, Maciej; Zielenkiewicz, Piotr; Siedlecki, Pawel

2015-01-01

There has been huge progress in the open cheminformatics field in both methods and software development. Unfortunately, there has been little effort to unite those methods and software into one package. We here describe the Open Drug Discovery Toolkit (ODDT), which aims to fulfill the need for comprehensive and open source drug discovery software. The Open Drug Discovery Toolkit was developed as a free and open source tool for both computer aided drug discovery (CADD) developers and researchers. ODDT reimplements many state-of-the-art methods, such as machine learning scoring functions (RF-Score and NNScore) and wraps other external software to ease the process of developing CADD pipelines. ODDT is an out-of-the-box solution designed to be easily customizable and extensible. Therefore, users are strongly encouraged to extend it and develop new methods. We here present three use cases for ODDT in common tasks in computer-aided drug discovery. Open Drug Discovery Toolkit is released on a permissive 3-clause BSD license for both academic and industrial use. ODDT's source code, additional examples and documentation are available on GitHub (https://github.com/oddt/oddt).

A Framework for Automatic Web Service Discovery Based on Semantics and NLP Techniques

Directory of Open Access Journals (Sweden)

Asma Adala

2011-01-01

Full Text Available As a greater number of Web Services are made available today, automatic discovery is recognized as an important task. To promote the automation of service discovery, different semantic languages have been created that allow describing the functionality of services in a machine interpretable form using Semantic Web technologies. The problem is that users do not have intimate knowledge about semantic Web service languages and related toolkits. In this paper, we propose a discovery framework that enables semantic Web service discovery based on keywords written in natural language. We describe a novel approach for automatic discovery of semantic Web services which employs Natural Language Processing techniques to match a user request, expressed in natural language, with a semantic Web service description. Additionally, we present an efficient semantic matching technique to compute the semantic distance between ontological concepts.

Work Stress Interventions in Hospital Care: Effectiveness of the DISCovery Method

Directory of Open Access Journals (Sweden)

Irene Niks

2018-02-01

Full Text Available Effective interventions to prevent work stress and to improve health, well-being, and performance of employees are of the utmost importance. This quasi-experimental intervention study presents a specific method for diagnosis of psychosocial risk factors at work and subsequent development and implementation of tailored work stress interventions, the so-called DISCovery method. This method aims at improving employee health, well-being, and performance by optimizing the balance between job demands, job resources, and recovery from work. The aim of the study is to quantitatively assess the effectiveness of the DISCovery method in hospital care. Specifically, we used a three-wave longitudinal, quasi-experimental multiple-case study approach with intervention and comparison groups in health care work. Positive changes were found for members of the intervention groups, relative to members of the corresponding comparison groups, with respect to targeted work-related characteristics and targeted health, well-being, and performance outcomes. Overall, results lend support for the effectiveness of the DISCovery method in hospital care.

Work Stress Interventions in Hospital Care: Effectiveness of the DISCovery Method.

Science.gov (United States)

Niks, Irene; de Jonge, Jan; Gevers, Josette; Houtman, Irene

2018-02-13

Effective interventions to prevent work stress and to improve health, well-being, and performance of employees are of the utmost importance. This quasi-experimental intervention study presents a specific method for diagnosis of psychosocial risk factors at work and subsequent development and implementation of tailored work stress interventions, the so-called DISCovery method. This method aims at improving employee health, well-being, and performance by optimizing the balance between job demands, job resources, and recovery from work. The aim of the study is to quantitatively assess the effectiveness of the DISCovery method in hospital care. Specifically, we used a three-wave longitudinal, quasi-experimental multiple-case study approach with intervention and comparison groups in health care work. Positive changes were found for members of the intervention groups, relative to members of the corresponding comparison groups, with respect to targeted work-related characteristics and targeted health, well-being, and performance outcomes. Overall, results lend support for the effectiveness of the DISCovery method in hospital care.

Work Stress Interventions in Hospital Care: Effectiveness of the DISCovery Method

Science.gov (United States)

Niks, Irene; Gevers, Josette

2018-01-01

Effective interventions to prevent work stress and to improve health, well-being, and performance of employees are of the utmost importance. This quasi-experimental intervention study presents a specific method for diagnosis of psychosocial risk factors at work and subsequent development and implementation of tailored work stress interventions, the so-called DISCovery method. This method aims at improving employee health, well-being, and performance by optimizing the balance between job demands, job resources, and recovery from work. The aim of the study is to quantitatively assess the effectiveness of the DISCovery method in hospital care. Specifically, we used a three-wave longitudinal, quasi-experimental multiple-case study approach with intervention and comparison groups in health care work. Positive changes were found for members of the intervention groups, relative to members of the corresponding comparison groups, with respect to targeted work-related characteristics and targeted health, well-being, and performance outcomes. Overall, results lend support for the effectiveness of the DISCovery method in hospital care. PMID:29438350

Sea Level Rise Data Discovery

Science.gov (United States)

Quach, N.; Huang, T.; Boening, C.; Gill, K. M.

2016-12-01

Research related to sea level rise crosses multiple disciplines from sea ice to land hydrology. The NASA Sea Level Change Portal (SLCP) is a one-stop source for current sea level change information and data, including interactive tools for accessing and viewing regional data, a virtual dashboard of sea level indicators, and ongoing updates through a suite of editorial products that include content articles, graphics, videos, and animations. The architecture behind the SLCP makes it possible to integrate web content and data relevant to sea level change that are archived across various data centers as well as new data generated by sea level change principal investigators. The Extensible Data Gateway Environment (EDGE) is incorporated into the SLCP architecture to provide a unified platform for web content and science data discovery. EDGE is a data integration platform designed to facilitate high-performance geospatial data discovery and access with the ability to support multi-metadata standard specifications. EDGE has the capability to retrieve data from one or more sources and package the resulting sets into a single response to the requestor. With this unified endpoint, the Data Analysis Tool that is available on the SLCP can retrieve dataset and granule level metadata as well as perform geospatial search on the data. This talk focuses on the architecture that makes it possible to seamlessly integrate and enable discovery of disparate data relevant to sea level rise.

The in silico drug discovery toolbox: applications in lead discovery and optimization.

Science.gov (United States)

Bruno, Agostino; Costantino, Gabriele; Sartori, Luca; Radi, Marco

2017-11-06

Discovery and development of a new drug is a long lasting and expensive journey that takes around 15 years from starting idea to approval and marketing of new medication. Despite the R&D expenditures have been constantly increasing in the last few years, number of new drugs introduced into market has been steadily declining. This is mainly due to preclinical and clinical safety issues, which still represent about 40% of drug discontinuation. From this point of view, it is clear that if we want to increase drug-discovery success rate and reduce costs associated with development of a new drug, a comprehensive evaluation/prediction of potential safety issues should be conducted as soon as possible during early drug discovery phase. In the present review, we will analyse the early steps of drug-discovery pipeline, describing the sequence of steps from disease selection to lead optimization and focusing on the most common in silico tools used to assess attrition risks and build a mitigation plan. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Academic Drug Discovery Centres

DEFF Research Database (Denmark)

Kirkegaard, Henriette Schultz; Valentin, Finn

2014-01-01

Academic drug discovery centres (ADDCs) are seen as one of the solutions to fill the innovation gap in early drug discovery, which has proven challenging for previous organisational models. Prior studies of ADDCs have identified the need to analyse them from the angle of their economic...

Service Discovery At Home

NARCIS (Netherlands)

Sundramoorthy, V.; Scholten, Johan; Jansen, P.G.; Hartel, Pieter H.

Service discovery is a fady new field that kicked off since the advent of ubiquitous computing and has been found essential in the making of intelligent networks by implementing automated discovery and remote control between deviies. This paper provides an ovewiew and comparison of several prominent

MedTime: a temporal information extraction system for clinical narratives.

Science.gov (United States)

Lin, Yu-Kai; Chen, Hsinchun; Brown, Randall A

2013-12-01

Temporal information extraction from clinical narratives is of critical importance to many clinical applications. We participated in the EVENT/TIMEX3 track of the 2012 i2b2 clinical temporal relations challenge, and presented our temporal information extraction system, MedTime. MedTime comprises a cascade of rule-based and machine-learning pattern recognition procedures. It achieved a micro-averaged f-measure of 0.88 in both the recognitions of clinical events and temporal expressions. We proposed and evaluated three time normalization strategies to normalize relative time expressions in clinical texts. The accuracy was 0.68 in normalizing temporal expressions of dates, times, durations, and frequencies. This study demonstrates and evaluates the integration of rule-based and machine-learning-based approaches for high performance temporal information extraction from clinical narratives. Copyright © 2013 Elsevier Inc. All rights reserved.

History of the discovery of the malaria parasites and their vectors

Directory of Open Access Journals (Sweden)

Cox Francis EG

2010-02-01

Full Text Available Abstract Malaria is caused by infection with protozoan parasites belonging to the genus Plasmodium transmitted by female Anopheles species mosquitoes. Our understanding of the malaria parasites begins in 1880 with the discovery of the parasites in the blood of malaria patients by Alphonse Laveran. The sexual stages in the blood were discovered by William MacCallum in birds infected with a related haematozoan, Haemoproteus columbae, in 1897 and the whole of the transmission cycle in culicine mosquitoes and birds infected with Plasmodium relictum was elucidated by Ronald Ross in 1897. In 1898 the Italian malariologists, Giovanni Battista Grassi, Amico Bignami, Giuseppe Bastianelli, Angelo Celli, Camillo Golgi and Ettore Marchiafava demonstrated conclusively that human malaria was also transmitted by mosquitoes, in this case anophelines. The discovery that malaria parasites developed in the liver before entering the blood stream was made by Henry Shortt and Cyril Garnham in 1948 and the final stage in the life cycle, the presence of dormant stages in the liver, was conclusively demonstrated in 1982 by Wojciech Krotoski. This article traces the main events and stresses the importance of comparative studies in that, apart from the initial discovery of parasites in the blood, every subsequent discovery has been based on studies on non-human malaria parasites and related organisms.

Synthetic biology of antimicrobial discovery.

Science.gov (United States)

Zakeri, Bijan; Lu, Timothy K

2013-07-19

Antibiotic discovery has a storied history. From the discovery of penicillin by Sir Alexander Fleming to the relentless quest for antibiotics by Selman Waksman, the stories have become like folklore used to inspire future generations of scientists. However, recent discovery pipelines have run dry at a time when multidrug-resistant pathogens are on the rise. Nature has proven to be a valuable reservoir of antimicrobial agents, which are primarily produced by modularized biochemical pathways. Such modularization is well suited to remodeling by an interdisciplinary approach that spans science and engineering. Herein, we discuss the biological engineering of small molecules, peptides, and non-traditional antimicrobials and provide an overview of the growing applicability of synthetic biology to antimicrobials discovery.

Temporally variable macroinvertebrate-stone relationships in streams

DEFF Research Database (Denmark)

Jacobsen, D.

2005-01-01

of fauna parameter and stone variable from different sampling dates (n=9-11) were rarely correlated to any of the measures of stream stability, this study has demonstrated high temporal variability in fauna-stone relationships (CV's of regression slopes). Consequently, temporally un-replicated studies......Stones were used to sample macroinvertebrates and characterise microhabitats at monthly or bimonthly intervals in six Ecuadorian streams covering a gradient in four different stability measures and other stream characteristics. The physical variables current velocity, water depth, horizontal...... of families vs. individuals) were related to the physical characteristics of individual stone habitats. My second objective was to quantify temporal variability in fauna-stone relationships and to analyse if such variability was related to overall stability of stream reaches. Partial Least Squares (PLS...

BLSSpeller: exhaustive comparative discovery of conserved cis-regulatory elements.

Science.gov (United States)

De Witte, Dieter; Van de Velde, Jan; Decap, Dries; Van Bel, Michiel; Audenaert, Pieter; Demeester, Piet; Dhoedt, Bart; Vandepoele, Klaas; Fostier, Jan

2015-12-01

The accurate discovery and annotation of regulatory elements remains a challenging problem. The growing number of sequenced genomes creates new opportunities for comparative approaches to motif discovery. Putative binding sites are then considered to be functional if they are conserved in orthologous promoter sequences of multiple related species. Existing methods for comparative motif discovery usually rely on pregenerated multiple sequence alignments, which are difficult to obtain for more diverged species such as plants. As a consequence, misaligned regulatory elements often remain undetected. We present a novel algorithm that supports both alignment-free and alignment-based motif discovery in the promoter sequences of related species. Putative motifs are exhaustively enumerated as words over the IUPAC alphabet and screened for conservation using the branch length score. Additionally, a confidence score is established in a genome-wide fashion. In order to take advantage of a cloud computing infrastructure, the MapReduce programming model is adopted. The method is applied to four monocotyledon plant species and it is shown that high-scoring motifs are significantly enriched for open chromatin regions in Oryza sativa and for transcription factor binding sites inferred through protein-binding microarrays in O.sativa and Zea mays. Furthermore, the method is shown to recover experimentally profiled ga2ox1-like KN1 binding sites in Z.mays. BLSSpeller was written in Java. Source code and manual are available at http://bioinformatics.intec.ugent.be/blsspeller Klaas.Vandepoele@psb.vib-ugent.be or jan.fostier@intec.ugent.be. Supplementary data are available at Bioinformatics online. © The Author 2015. Published by Oxford University Press.

Suboptimal choice, reward-predictive signals, and temporal information.

Science.gov (United States)

Cunningham, Paul J; Shahan, Timothy A

2018-01-01

Suboptimal choice refers to preference for an alternative offering a low probability of food (suboptimal alternative) over an alternative offering a higher probability of food (optimal alternative). Numerous studies have found that stimuli signaling probabilistic food play a critical role in the development and maintenance of suboptimal choice. However, there is still much debate about how to characterize how these stimuli influence suboptimal choice. There is substantial evidence that the temporal information conveyed by a food-predictive signal governs its function as both a Pavlovian conditioned stimulus and as an instrumental conditioned reinforcer. Thus, we explore the possibility that food-predictive signals influence suboptimal choice via the temporal information they convey. Application of this temporal information-theoretic approach to suboptimal choice provides a formal, quantitative framework that describes how food-predictive signals influence suboptimal choice in a manner consistent with related phenomena in Pavlovian conditioning and conditioned reinforcement. Our reanalysis of previous data on suboptimal choice suggests that, generally speaking, preference in the suboptimal choice procedure tracks relative temporal information conveyed by food-predictive signals for the suboptimal and optimal alternatives. The model suggests that suboptimal choice develops when the food-predictive signal for the suboptimal alternative conveys more temporal information than that for the optimal alternative. Finally, incorporating a role for competition between temporal information provided by food-predictive signals and relative primary reinforcement rate provides a reasonable account of existing data on suboptimal choice. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Incremental temporal pattern mining using efficient batch-free stream clustering

NARCIS (Netherlands)

Lu, Y.; Hassani, M.; Seidl, T.

2017-01-01

This paper address the problem of temporal pattern mining from multiple data streams containing temporal events. Temporal events are considered as real world events aligned with comprehensive starting and ending timing information rather than simple integer timestamps. Predefined relations, such as

[Advances in research on cognitive function related to temporal lobe epilepsy: focus on social cognitive function].

Science.gov (United States)

Yamano, Mitsuhiko; Akamatsu, Naoki; Tsuji, Sadatoshi

2012-09-01

Research on cognitive function related to temporal lobe epilepsy has thus far focused on memory, language, and general intelligence. Recently, however, the concept of social cognitive function has been proposed in the field of neuropsychology. Social cognitive function refers collectively to the higher cognitive functions that are essential in our social lives, and its representative aspects are facial expression recognition and decision-making. Emotional processing centered around the amygdala is thought to play a key role in the neural mechanism of this function. We conducted a study on the social cognitive function (decision-making) of patients with temporal lobe epilepsy, and found that this function is reduced in these patients, and that the right amygdalo-hippocampal complexes play an important role. In order to ensure the best possible treatment for epilepsy patients, it is necessary not only to make an accurate diagnosis and provide appropriate treatment, but also to provide support for enabling a smoother social life from the perspective of social cognitive function. Future research developments in this field are expected to contribute to total management in medical care for epilepsy patients.

Discovery of functional elements in 12 Drosophila genomes using evolutionary signatures

DEFF Research Database (Denmark)

Stark, Alexander; Lin, Michael F; Kheradpour, Pouya

2007-01-01

Sequencing of multiple related species followed by comparative genomics analysis constitutes a powerful approach for the systematic understanding of any genome. Here, we use the genomes of 12 Drosophila species for the de novo discovery of functional elements in the fly. Each type of functional e...... individual motif instances with high confidence. We also study how discovery power scales with the divergence and number of species compared, and we provide general guidelines for comparative studies....

Using the relational event model (REM) to investigate the temporal dynamics of animal social networks.

Science.gov (United States)

Tranmer, Mark; Marcum, Christopher Steven; Morton, F Blake; Croft, Darren P; de Kort, Selvino R

2015-03-01

Social dynamics are of fundamental importance in animal societies. Studies on nonhuman animal social systems often aggregate social interaction event data into a single network within a particular time frame. Analysis of the resulting network can provide a useful insight into the overall extent of interaction. However, through aggregation, information is lost about the order in which interactions occurred, and hence the sequences of actions over time. Many research hypotheses relate directly to the sequence of actions, such as the recency or rate of action, rather than to their overall volume or presence. Here, we demonstrate how the temporal structure of social interaction sequences can be quantified from disaggregated event data using the relational event model (REM). We first outline the REM, explaining why it is different from other models for longitudinal data, and how it can be used to model sequences of events unfolding in a network. We then discuss a case study on the European jackdaw, Corvus monedula , in which temporal patterns of persistence and reciprocity of action are of interest, and present and discuss the results of a REM analysis of these data. One of the strengths of a REM analysis is its ability to take into account different ways in which data are collected. Having explained how to take into account the way in which the data were collected for the jackdaw study, we briefly discuss the application of the model to other studies. We provide details of how the models may be fitted in the R statistical software environment and outline some recent extensions to the REM framework.

Temporal association between the isolation of Sabin-related poliovirus vaccine strains and the Guillain-Barré syndrome

Directory of Open Access Journals (Sweden)

F. Friedrich

1996-02-01

Full Text Available Thirty eight paralysis cases classified as Guillain-Barré syndrome (GBS in Brazil were analysed. In all these cases Sabin-related poliovirus vaccine strains were isolated. In most of the cases the last vaccine dose was given months or years before the onset of GBS, suggesting a persistent infection or the transmission of the Sabin-related strains to the patients. The isolation of Sabin-related strains from GBS cases some days or weeks after the onset of the disease, demonstrated a temporal association between the isolation of the strains and the disease. Although the isolates from the GBS cases may not be the etiological agent of the disease, this study strongly indicates that infections caused by Sabin-related vaccine strains can trigger the GBS in certain cases.

PCSK9: From Basic Science Discoveries to Clinical Trials.

Science.gov (United States)

Shapiro, Michael D; Tavori, Hagai; Fazio, Sergio

2018-05-11

Unknown 15 years ago, PCSK9 (proprotein convertase subtilisin/kexin type 9) is now common parlance among scientists and clinicians interested in prevention and treatment of atherosclerotic cardiovascular disease. What makes this story so special is not its recent discovery nor the fact that it uncovered previously unknown biology but rather that these important scientific insights have been translated into an effective medical therapy in record time. Indeed, the translation of this discovery to novel therapeutic serves as one of the best examples of how genetic insights can be leveraged into intelligent target drug discovery. The PCSK9 saga is unfolding quickly but is far from complete. Here, we review major scientific understandings as they relate to the role of PCSK9 in lipoprotein metabolism and atherosclerotic cardiovascular disease and the impact that therapies designed to inhibit its action are having in the clinical setting. © 2018 American Heart Association, Inc.

Anthelmintics: From discovery to resistance II (San Diego, 2016

Directory of Open Access Journals (Sweden)

Richard J. Martin

2016-12-01

Full Text Available The second scientific meeting in the series: “Anthelmintics: From Discovery to Resistance” was held in San Diego in February, 2016. The focus topics of the meeting, related to anthelmintic discovery and resistance, were novel technologies, bioinformatics, commercial interests, anthelmintic modes of action and anthelmintic resistance. Basic scientific, human and veterinary interests were addressed in oral and poster presentations. The delegates were from universities and industries in the US, Europe, Australia and New Zealand. The papers were a great representation of the field, and included the use of C. elegans for lead discovery, mechanisms of anthelmintic resistance, nematode neuropeptides, proteases, B. thuringiensis crystal protein, nicotinic receptors, emodepside, benzimidazoles, P-glycoproteins, natural products, microfluidic techniques and bioinformatics approaches. The NIH also presented NIAID-specific parasite genomic priorities and initiatives. From these papers we introduce below selected papers with a focus on anthelmintic drug screening and development.

The discovery of radioactivity: the centenary

International Nuclear Information System (INIS)

Patil, S.K.

1995-01-01

In the last decade of the nineteenth century, a number of fundamental discoveries of outstanding importance were made unexpectedly which marked the beginning of a new era in physics. A cascade of spectacular discoveries began with the announcement of the discovery of x-rays by Roentgen followed by the discoveries, in quick succession, of radioactivity by Becquerel, of Zeeman effect, of electron by J.J. Thomson, and of polonium and radium by the Curies. Both x-rays and radioactivity have wide applications in scientific, medical and industrial fields and have made outstanding contribution to the advancement of human knowledge and welfare. Radioactivity is well known and no other discovery in the field of physics or chemistry has had a more profound effect on our fundamental knowledge of nature. Present article, on the occasion of the centenary of the discovery of radioactivity, makes an attempt to describe some glimpses of the history of radioactivity. (author). 59 refs

The π discovery

International Nuclear Information System (INIS)

Fowler, P.H.

1988-01-01

The paper traces the discovery of the Π meson. The discovery was made by exposure of nuclear emulsions to cosmic radiation at high altitudes, with subsequent scanning of the emulsions for meson tracks. Disintegration of nuclei by a negative meson, and the decay of a Π meson were both observed. Further measurements revealed the mass of the meson. The studies carried out on the origin of the Π-mesons, and their mode of decay, are both described. (U.K.)

Temporal Lobe Epilepsy in Children

Science.gov (United States)

Nickels, Katherine C.; Wong-Kisiel, Lily C.; Moseley, Brian D.; Wirrell, Elaine C.

2012-01-01

The temporal lobe is a common focus for epilepsy. Temporal lobe epilepsy in infants and children differs from the relatively homogeneous syndrome seen in adults in several important clinical and pathological ways. Seizure semiology varies by age, and the ictal EEG pattern may be less clear cut than what is seen in adults. Additionally, the occurrence of intractable seizures in the developing brain may impact neurocognitive function remote from the temporal area. While many children will respond favorably to medical therapy, those with focal imaging abnormalities including cortical dysplasia, hippocampal sclerosis, or low-grade tumors are likely to be intractable. Expedient workup and surgical intervention in these medically intractable cases are needed to maximize long-term developmental outcome. PMID:22957247

Temporal hypometabolism at the onset of cryptogenic temporal lobe epilepsy

Energy Technology Data Exchange (ETDEWEB)

Matheja, P.; Kuwert, T.; Weckesser, M.; Schober, O. [Dept. of Nuclear Medicine, Muenster Univ. (Germany); Luedemann, P.; Kellinghaus, C.; Diehl, B.; Ringelstein, E.B. [Dept. of Neurology, Muenster Univ. (Germany); Schuierer, G. [Dept. of Clinical Radiology, Muenster Univ. (Germany)

2001-05-01

Most patients with intractable temporal lobe epilepsy (TLE) exhibit temporal glucose hypometabolism. The reasons for the development of this abnormality are as yet unclear. The current notion is that an initial injury causes seizures, which in turn give rise to hypometabolism. The aim of this study was to assess whether temporal reductions in glucose metabolism in non-lesional TLE are the result of repeated seizures or whether hypometabolism represents an initial disturbance at the onset of disease. Glucose consumption was assessed with fluorine-18 fluorodeoxyglucose positron emission tomography ({sup 18}F-FDG PET) in 62 patients with cryptogenic non-refractory TLE in different stages of disease. Twelve subjects without neurological illness served as controls. Patients with onset of epilepsy at least 3 years prior to the PET scan were defined as having chronic TLE. Using this criterion, the whole patient cohort included 27 patients with de novo TLE and 35 patients with chronic TLE. The groups were matched for age and sex. The appearance of high-resolution magnetic resonance images of the brain was unremarkable in all patients. In the total cohort, number, duration and frequency of seizures had a significant relation to the magnitude of hypometabolism. Temporal hypometabolism was exhibited by 26 of the 62 patients (42%), including 8 out of 27 (30%) with newly diagnosed TLE and 18 out of 35 (51%) with chronic TLE. The disturbances were more extensive and more severe in patients with chronic TLE. It is concluded that temporal hypometabolism may already be present at the onset of TLE, but is less frequent and less severe in newly diagnosed than in chronic TLE. The metabolic disturbance correlates with the number of seizures. These findings suggest that an initial dysfunction is present in a considerable number of patients and that hypometabolism is worsened by continuing epileptic activity. (orig.)

Synthetic biology of antimicrobial discovery

Science.gov (United States)

Zakeri, Bijan; Lu, Timothy K.

2012-01-01

Antibiotic discovery has a storied history. From the discovery of penicillin by Sir Alexander Fleming to the relentless quest for antibiotics by Selman Waksman, the stories have become like folklore, used to inspire future generations of scientists. However, recent discovery pipelines have run dry at a time when multidrug resistant pathogens are on the rise. Nature has proven to be a valuable reservoir of antimicrobial agents, which are primarily produced by modularized biochemical pathways. Such modularization is well suited to remodeling by an interdisciplinary approach that spans science and engineering. Herein, we discuss the biological engineering of small molecules, peptides, and non-traditional antimicrobials and provide an overview of the growing applicability of synthetic biology to antimicrobials discovery. PMID:23654251

Isolating Exogenous and Endogenous Modes of Temporal Attention

Science.gov (United States)

Lawrence, Michael A.; Klein, Raymond M.

2013-01-01

The differential allocation of information processing resources over time, here termed "temporal attention," may be achieved by relatively automatic "exogenous" or controlled "endogenous" mechanisms. Over 100 years of research has confounded these theoretically distinct dimensions of temporal attention. The current…

TEMPTING system: a hybrid method of rule and machine learning for temporal relation extraction in patient discharge summaries.

Science.gov (United States)

Chang, Yung-Chun; Dai, Hong-Jie; Wu, Johnny Chi-Yang; Chen, Jian-Ming; Tsai, Richard Tzong-Han; Hsu, Wen-Lian

2013-12-01

Patient discharge summaries provide detailed medical information about individuals who have been hospitalized. To make a precise and legitimate assessment of the abundant data, a proper time layout of the sequence of relevant events should be compiled and used to drive a patient-specific timeline, which could further assist medical personnel in making clinical decisions. The process of identifying the chronological order of entities is called temporal relation extraction. In this paper, we propose a hybrid method to identify appropriate temporal links between a pair of entities. The method combines two approaches: one is rule-based and the other is based on the maximum entropy model. We develop an integration algorithm to fuse the results of the two approaches. All rules and the integration algorithm are formally stated so that one can easily reproduce the system and results. To optimize the system's configuration, we used the 2012 i2b2 challenge TLINK track dataset and applied threefold cross validation to the training set. Then, we evaluated its performance on the training and test datasets. The experiment results show that the proposed TEMPTING (TEMPoral relaTion extractING) system (ranked seventh) achieved an F-score of 0.563, which was at least 30% better than that of the baseline system, which randomly selects TLINK candidates from all pairs and assigns the TLINK types. The TEMPTING system using the hybrid method also outperformed the stage-based TEMPTING system. Its F-scores were 3.51% and 0.97% better than those of the stage-based system on the training set and test set, respectively. Copyright © 2013 Elsevier Inc. All rights reserved.

'The Lusiads', poem of discovery

Directory of Open Access Journals (Sweden)

Natasha Furlan Felizi

2016-07-01

Full Text Available The article proposes reading Os Lusíadas as a discovery journey. Discovery here read as aletheia or “revelation”, as proposed by Sophia de Mello Brey­ner Andresen in 1980. Using Martin Heidegger’s notion of aletheia in the book Parmenides along with Jorge de Sena and Sophia de Mello Breyner Andresen reflections on Camões, I’ll seek to point out alternative readings for Os Lusíadas as a “discovery journey”.

Computational methods in drug discovery

OpenAIRE

Sumudu P. Leelananda; Steffen Lindert

2016-01-01

The process for drug discovery and development is challenging, time consuming and expensive. Computer-aided drug discovery (CADD) tools can act as a virtual shortcut, assisting in the expedition of this long process and potentially reducing the cost of research and development. Today CADD has become an effective and indispensable tool in therapeutic development. The human genome project has made available a substantial amount of sequence data that can be used in various drug discovery project...

Temporal subtraction of dual-energy chest radiographs

International Nuclear Information System (INIS)

Armato, Samuel G. III; Doshi, Devang J.; Engelmann, Roger; Caligiuri, Philip; MacMahon, Heber

2006-01-01

Temporal subtraction and dual-energy imaging are two enhanced radiography techniques that are receiving increased attention in chest radiography. Temporal subtraction is an image processing technique that facilitates the visualization of pathologic change across serial chest radiographic images acquired from the same patient; dual-energy imaging exploits the differential relative attenuation of x-ray photons exhibited by soft-tissue and bony structures at different x-ray energies to generate a pair of images that accentuate those structures. Although temporal subtraction images provide a powerful mechanism for enhancing visualization of subtle change, misregistration artifacts in these images can mimic or obscure abnormalities. The purpose of this study was to evaluate whether dual-energy imaging could improve the quality of temporal subtraction images. Temporal subtraction images were generated from 100 pairs of temporally sequential standard radiographic chest images and from the corresponding 100 pairs of dual-energy, soft-tissue radiographic images. The registration accuracy demonstrated in the resulting temporal subtraction images was evaluated subjectively by two radiologists. The registration accuracy of the soft-tissue-based temporal subtraction images was rated superior to that of the conventional temporal subtraction images. Registration accuracy also was evaluated objectively through an automated method, which achieved an area-under-the-ROC-curve value of 0.92 in the distinction between temporal subtraction images that demonstrated clinically acceptable and clinically unacceptable registration accuracy. By combining dual-energy soft-tissue images with temporal subtraction, misregistration artifacts can be reduced and superior image quality can be obtained

Choosing Discovery: A Literature Review on the Selection and Evaluation of Discovery Layers

Science.gov (United States)

Moore, Kate B.; Greene, Courtney

2012-01-01

Within the next few years, traditional online public access catalogs will be replaced by more robust and interconnected discovery layers that can serve as primary public interfaces to simultaneously search many separate collections of resources. Librarians have envisioned this type of discovery tool since the 1980s, and research shows that…

Discovery of omega meson, first neutral vector meson

International Nuclear Information System (INIS)

Anon.

1976-01-01

A personal account of the discovery of the ω meson is given by researcher B. Maglich. His account includes such topics as early and unsuccessful searches for a neutral vector meson (by himself and others), eventual discovery of the rho meson, the Goldhaber effect, and the observation and characterization of the ω meson. Explanatory physics notes on electromagnetic structure experiments and the determination of the quantum numbers of the ω meson are provided for nonspecialists. Also included are an outline of the relation between vector mesons and nuclear forces, a reprint of the Physical Review Letter on Evidence for a T = 0 three-pion resonance, and a scientific autobiography of the researcher. 14 figures, 1 table

Investigations into Library Web-Scale Discovery Services

Directory of Open Access Journals (Sweden)

Jason Vaughan

2008-03-01

Full Text Available Web-scale discovery services for libraries provide deep discovery to a library’s local and licensed content, and represent an evolution, perhaps a revolution, for end user information discovery as pertains to library collections.  This article frames the topic of web-scale discovery, and begins by illuminating web-scale discovery from an academic library’s perspective – that is, the internal perspective seeking widespread staff participation in the discovery conversation.  This included the creation of a discovery task force, a group which educated library staff, conducted internal staff surveys, and gathered observations from early adopters.  The article next addresses the substantial research conducted with library vendors which have developed these services.  Such work included drafting of multiple comprehensive question lists distributed to the vendors, onsite vendor visits, and continual tracking of service enhancements.  Together, feedback gained from library staff, insights arrived at by the Discovery Task Force, and information gathered from vendors collectively informed the recommendation of a service for the UNLV Libraries.

The Europa Ocean Discovery mission

Energy Technology Data Exchange (ETDEWEB)

Edwards, B.C. [Los Alamos National Lab., NM (United States); Chyba, C.F. [Univ. of Arizona, Tucson, AZ (United States); Abshire, J.B. [National Aeronautics and Space Administration, Greenbelt, MD (United States). Goddard Space Flight Center] [and others

1997-06-01

Since it was first proposed that tidal heating of Europa by Jupiter might lead to liquid water oceans below Europa`s ice cover, there has been speculation over the possible exobiological implications of such an ocean. Liquid water is the essential ingredient for life as it is known, and the existence of a second water ocean in the Solar System would be of paramount importance for seeking the origin and existence of life beyond Earth. The authors present here a Discovery-class mission concept (Europa Ocean Discovery) to determine the existence of a liquid water ocean on Europa and to characterize Europa`s surface structure. The technical goal of the Europa Ocean Discovery mission is to study Europa with an orbiting spacecraft. This goal is challenging but entirely feasible within the Discovery envelope. There are four key challenges: entering Europan orbit, generating power, surviving long enough in the radiation environment to return valuable science, and complete the mission within the Discovery program`s launch vehicle and budget constraints. The authors will present here a viable mission that meets these challenges.

29 CFR 18.13 - Discovery methods.

Science.gov (United States)

2010-07-01

... 29 Labor 1 2010-07-01 2010-07-01 true Discovery methods. 18.13 Section 18.13 Labor Office of the... ADMINISTRATIVE LAW JUDGES General § 18.13 Discovery methods. Parties may obtain discovery by one or more of the following methods: Depositions upon oral examination or written questions; written interrogatories...

Discovery of the neutron (to the fiftieth anniversary of neutron discovery)

International Nuclear Information System (INIS)

Pasechnik, M.V.

1984-01-01

Development of neutron physics in the USSR for the recent 50 years from the moment of neutron discovery is considered. History of neutron discovery is presented in brief. Neutron properties and fundamental problems of physics: electric dipole neutron moment, neutron β-decay, neutron interaction with nuclei and potential of nucleon interaction not conserving spatial parity are discussed. Main aspects of neutron physics application in power engineering, nuclear technology and other branches of science and technique are set forth

Analysis of Temporal-spatial Co-variation within Gene Expression Microarray Data in an Organogenesis Model

Science.gov (United States)

Ehler, Martin; Rajapakse, Vinodh; Zeeberg, Barry; Brooks, Brian; Brown, Jacob; Czaja, Wojciech; Bonner, Robert F.

The gene networks underlying closure of the optic fissure during vertebrate eye development are poorly understood. We used a novel clustering method based on Laplacian Eigenmaps, a nonlinear dimension reduction method, to analyze microarray data from laser capture microdissected (LCM) cells at the site and developmental stages (days 10.5 to 12.5) of optic fissure closure. Our new method provided greater biological specificity than classical clustering algorithms in terms of identifying more biological processes and functions related to eye development as defined by Gene Ontology at lower false discovery rates. This new methodology builds on the advantages of LCM to isolate pure phenotypic populations within complex tissues and allows improved ability to identify critical gene products expressed at lower copy number. The combination of LCM of embryonic organs, gene expression microarrays, and extracting spatial and temporal co-variations appear to be a powerful approach to understanding the gene regulatory networks that specify mammalian organogenesis.

Object-graphs for context-aware visual category discovery.

Science.gov (United States)

Lee, Yong Jae; Grauman, Kristen

2012-02-01

How can knowing about some categories help us to discover new ones in unlabeled images? Unsupervised visual category discovery is useful to mine for recurring objects without human supervision, but existing methods assume no prior information and thus tend to perform poorly for cluttered scenes with multiple objects. We propose to leverage knowledge about previously learned categories to enable more accurate discovery, and address challenges in estimating their familiarity in unsegmented, unlabeled images. We introduce two variants of a novel object-graph descriptor to encode the 2D and 3D spatial layout of object-level co-occurrence patterns relative to an unfamiliar region and show that by using them to model the interaction between an image’s known and unknown objects, we can better detect new visual categories. Rather than mine for all categories from scratch, our method identifies new objects while drawing on useful cues from familiar ones. We evaluate our approach on several benchmark data sets and demonstrate clear improvements in discovery over conventional purely appearance-based baselines.

Mesial temporal sclerosis in children Esclerose mesial temporal em crianças

Directory of Open Access Journals (Sweden)

Eliana Maria Domingues Brandão

2007-12-01

Full Text Available Mesial temporal sclerosis is the most frequent cause of drug-resistant temporal lobe epilepsy but has a satisfactory response to surgery, and is considered infrequent in children. OBJECTIVE: To evaluate the clinical, electrographic and radiological spectrum of the disease in children. METHOD: Retrospective study by review of charts of 44 children with a diagnosis of mesial temporal sclerosis on magnetic resonance imaging, attended at the "Hospital das Clínicas" of the University of São Paulo Faculty of Medicine. RESULTS: Febrile seizure was identified in the history of 54% of the patients. Injuries at the left side predominated in patients with schooling difficulties (p=0.049, in those with the first seizures between six months and five years (p=0.021 and in those with complex febrile seizure (p=0.032. Thirteen patients were submitted to surgery and of these, eight remained without seizures. CONCLUSION: Febrile seizure may be related in a more direct way to the presence of left-side mesial temporal sclerosis.Em adultos, esclerose mesial temporal é a causa mais freqüente de epilepsia do lobo temporal intratável por medicamentos e que responde satisfatoriamente a cirurgia, sendo considerada pouco freqüente em criança. OBJETIVO: Avaliar o espectro clínico, eletrográfico e radiológico desta patologia em crianças. MÉTODO: Estudo retrospectivo, por revisão de prontuário de 44 crianças com diagnóstico de esclerose mesial temporal na ressonância magnética, atendidos no Hospital das Clínicas da Faculdade de Medicina de São Paulo. RESULTADO: Foi identificado que 54% dos pacientes apresentaram antecedente de crise febril. Lesão no lado esquerdo predominou nos pacientes com dificuldade escolar (p=0.049, naqueles com primeiras crises entre seis meses e cinco anos (p=0,021 e naqueles com crise febril complicada (p=0,032. Treze pacientes foram operados, dos quais oito ficaram livres de crises. CONCLUSÃO: Crise febril pode estar

Discovery of Approximate Differential Dependencies

OpenAIRE

Liu, Jixue; Kwashie, Selasi; Li, Jiuyong; Ye, Feiyue; Vincent, Millist

2013-01-01

Differential dependencies (DDs) capture the relationships between data columns of relations. They are more general than functional dependencies (FDs) and and the difference is that DDs are defined on the distances between values of two tuples, not directly on the values. Because of this difference, the algorithms for discovering FDs from data find only special DDs, not all DDs and therefore are not applicable to DD discovery. In this paper, we propose an algorithm to discover DDs from data fo...

41 CFR 60-30.33 - Discovery.

Science.gov (United States)

2010-07-01

... 41 Public Contracts and Property Management 1 2010-07-01 2010-07-01 true Discovery. 60-30.33... 11246 Expedited Hearing Procedures § 60-30.33 Discovery. (a) Any party may serve requests for admissions... with § 60-30.8, the Administrative Law Judge may allow the taking of depositions. Other discovery will...

Representation Discovery using Harmonic Analysis

CERN Document Server

Mahadevan, Sridhar

2008-01-01

Representations are at the heart of artificial intelligence (AI). This book is devoted to the problem of representation discovery: how can an intelligent system construct representations from its experience? Representation discovery re-parameterizes the state space - prior to the application of information retrieval, machine learning, or optimization techniques - facilitating later inference processes by constructing new task-specific bases adapted to the state space geometry. This book presents a general approach to representation discovery using the framework of harmonic analysis, in particu

tOWL: a temporal Web Ontology Language.

Science.gov (United States)

Milea, Viorel; Frasincar, Flavius; Kaymak, Uzay

2012-02-01

Through its interoperability and reasoning capabilities, the Semantic Web opens a realm of possibilities for developing intelligent systems on the Web. The Web Ontology Language (OWL) is the most expressive standard language for modeling ontologies, the cornerstone of the Semantic Web. However, up until now, no standard way of expressing time and time-dependent information in OWL has been provided. In this paper, we present a temporal extension of the very expressive fragment SHIN(D) of the OWL Description Logic language, resulting in the temporal OWL language. Through a layered approach, we introduce three extensions: 1) concrete domains, which allow the representation of restrictions using concrete domain binary predicates; 2) temporal representation , which introduces time points, relations between time points, intervals, and Allen's 13 interval relations into the language; and 3) timeslices/fluents, which implement a perdurantist view on individuals and allow for the representation of complex temporal aspects, such as process state transitions. We illustrate the expressiveness of the newly introduced language by using an example from the financial domain.

Antibody informatics for drug discovery

DEFF Research Database (Denmark)

Shirai, Hiroki; Prades, Catherine; Vita, Randi

2014-01-01

to the antibody science in every project in antibody drug discovery. Recent experimental technologies allow for the rapid generation of large-scale data on antibody sequences, affinity, potency, structures, and biological functions; this should accelerate drug discovery research. Therefore, a robust bioinformatic...... infrastructure for these large data sets has become necessary. In this article, we first identify and discuss the typical obstacles faced during the antibody drug discovery process. We then summarize the current status of three sub-fields of antibody informatics as follows: (i) recent progress in technologies...... for antibody rational design using computational approaches to affinity and stability improvement, as well as ab-initio and homology-based antibody modeling; (ii) resources for antibody sequences, structures, and immune epitopes and open drug discovery resources for development of antibody drugs; and (iii...

45 CFR 213.23a - Discovery.

Science.gov (United States)

2010-10-01

... 45 Public Welfare 2 2010-10-01 2010-10-01 false Discovery. 213.23a Section 213.23a Public Welfare... Discovery. The Department and any party named in the notice issued pursuant to § 213.11 shall have the right to conduct discovery (including depositions) against opposing parties. Rules 26-37 of the Federal...

Fragment-based drug discovery and its application to challenging drug targets.

Science.gov (United States)

Price, Amanda J; Howard, Steven; Cons, Benjamin D

2017-11-08

Fragment-based drug discovery (FBDD) is a technique for identifying low molecular weight chemical starting points for drug discovery. Since its inception 20 years ago, FBDD has grown in popularity to the point where it is now an established technique in industry and academia. The approach involves the biophysical screening of proteins against collections of low molecular weight compounds (fragments). Although fragments bind to proteins with relatively low affinity, they form efficient, high quality binding interactions with the protein architecture as they have to overcome a significant entropy barrier to bind. Of the biophysical methods available for fragment screening, X-ray protein crystallography is one of the most sensitive and least prone to false positives. It also provides detailed structural information of the protein-fragment complex at the atomic level. Fragment-based screening using X-ray crystallography is therefore an efficient method for identifying binding hotspots on proteins, which can then be exploited by chemists and biologists for the discovery of new drugs. The use of FBDD is illustrated here with a recently published case study of a drug discovery programme targeting the challenging protein-protein interaction Kelch-like ECH-associated protein 1:nuclear factor erythroid 2-related factor 2. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

The scientist as philosopher philosophical consequences of great scientific discoveries

CERN Document Server

Weinert, Friedel

2005-01-01

How do major scientific discoveries reshape their originators’, and our own, sense of reality and concept of the physical world? The Scientist as Philosopher explores the interaction between physics and philosophy. Clearly written and well illustrated, the book first places the scientist-philosophers in the limelight as we learn how their great scientific discoveries forced them to reconsider the time-honored notions with which science had described the natural world. Then, the book explains that what we understand by nature and science have undergone fundamental conceptual changes as a result of the discoveries of electromagnetism, thermodynamics and atomic structure. Even more dramatically, the quantum theory and special theory of relativity questioned traditional assumptions about causation and the passage of time. The author concludes that the dance between science and philosophy is an evolutionary process, which will keep them forever entwined.

SemaTyP: a knowledge graph based literature mining method for drug discovery.

Science.gov (United States)

Sang, Shengtian; Yang, Zhihao; Wang, Lei; Liu, Xiaoxia; Lin, Hongfei; Wang, Jian

2018-05-30

Drug discovery is the process through which potential new medicines are identified. High-throughput screening and computer-aided drug discovery/design are the two main drug discovery methods for now, which have successfully discovered a series of drugs. However, development of new drugs is still an extremely time-consuming and expensive process. Biomedical literature contains important clues for the identification of potential treatments. It could support experts in biomedicine on their way towards new discoveries. Here, we propose a biomedical knowledge graph-based drug discovery method called SemaTyP, which discovers candidate drugs for diseases by mining published biomedical literature. We first construct a biomedical knowledge graph with the relations extracted from biomedical abstracts, then a logistic regression model is trained by learning the semantic types of paths of known drug therapies' existing in the biomedical knowledge graph, finally the learned model is used to discover drug therapies for new diseases. The experimental results show that our method could not only effectively discover new drug therapies for new diseases, but also could provide the potential mechanism of action of the candidate drugs. In this paper we propose a novel knowledge graph based literature mining method for drug discovery. It could be a supplementary method for current drug discovery methods.

Unilateral mesial temporal atrophy after a systemic insult as a possible etiology of refractory temporal lobe epilepsy: case report Esclerose mesial temporal unilateral após insulto sistêmico como possível etiologia de epilepsia refratária do lobo temporal: relato de caso

Directory of Open Access Journals (Sweden)

Arthur Cukiert

1997-09-01

Full Text Available Mesial temporal sclerosis is the main pathological substrate present in refractory temporal lobe epilepsy and its presence is often related to the occurrence of febrile seizures in infancy. There is an on-going discussion on the nature of mesial temporal sclerosis as it related to epilepsy: cause or consequence. A previously normal child developed hyperosmolar coma after abdominal surgery at the age of 6. Three months afterwards he developed simple and complex partial seizures with an increasing frequency and refractory to multiple mono-and polytherapic drug regimens. He was evaluated for surgery at the age of 13. Ictal and interictal recordings showed left temporal lobe abnormalities. Early CT scaning suggested left temporal atrophy. MRI showed mesial temporal sclerosis. Neuropsichological testing showed verbal memory deficits and he passed a left carotid artery amytal injection. He was submitted to a cortico-amygdalo-hippocampectomy and has been seizure-free since then. The clinical data obtained from this patient suggest that at least in this case mesial temporal sclerosis would be related to the cause of epilepsy and not resultant from repeated seizure activity.A esclerose mesial temporal é o principal substrato anatomo-patológico envolvido na epilepsia refratária do lobo temporal e está frequentemente associada à ocorrência de convulsões febris na infância. Persiste até o momento intensa discussão se a esclerose mesial seria causa ou consequência da síndrome epiléptica. Uma criança previamente normal, desenvolveu coma hiperosmolar após intercorrência em cirurgia abdominal aos 6 anos de idade. Após 3 meses iniciaram-se crises parciais simples e complexas em frequência ascendente e refratárias a múltiplos esquemas terapêuticos em mono- e politerapia. Ele realizou investigação pré-operatória para epilepsia aos 13 anos de idade. Registros eletrencefalográficos de superfície ictais e interictais mostraram anormalidades

The role of temporal structure in human vision.

Science.gov (United States)

Blake, Randolph; Lee, Sang-Hun

2005-03-01

Gestalt psychologists identified several stimulus properties thought to underlie visual grouping and figure/ground segmentation, and among those properties was common fate: the tendency to group together individual objects that move together in the same direction at the same speed. Recent years have witnessed an upsurge of interest in visual grouping based on other time-dependent sources of visual information, including synchronized changes in luminance, in motion direction, and in figure/ ground relations. These various sources of temporal grouping information can be subsumed under the rubric temporal structure. In this article, the authors review evidence bearing on the effectiveness of temporal structure in visual grouping. They start with an overview of evidence bearing on temporal acuity of human vision, covering studies dealing with temporal integration and temporal differentiation. They then summarize psychophysical studies dealing with figure/ground segregation based on temporal phase differences in deterministic and stochastic events. The authors conclude with a brief discussion of neurophysiological implications of these results.

Second-order analysis of structured inhomogeneous spatio-temporal point processes

DEFF Research Database (Denmark)

Møller, Jesper; Ghorbani, Mohammad

Statistical methodology for spatio-temporal point processes is in its infancy. We consider second-order analysis based on pair correlation functions and K-functions for first general inhomogeneous spatio-temporal point processes and second inhomogeneous spatio-temporal Cox processes. Assuming...... spatio-temporal separability of the intensity function, we clarify different meanings of second-order spatio-temporal separability. One is second-order spatio-temporal independence and relates e.g. to log-Gaussian Cox processes with an additive covariance structure of the underlying spatio......-temporal Gaussian process. Another concerns shot-noise Cox processes with a separable spatio-temporal covariance density. We propose diagnostic procedures for checking hypotheses of second-order spatio-temporal separability, which we apply on simulated and real data (the UK 2001 epidemic foot and mouth disease data)....

Spatio-temporal variability of the North Sea cod recruitment in relation to temperature and zooplankton.

Directory of Open Access Journals (Sweden)

Delphine Nicolas

Full Text Available The North Sea cod (Gadus morhua, L. stock has continuously declined over the past four decades linked with overfishing and climate change. Changes in stock structure due to overfishing have made the stock largely dependent on its recruitment success, which greatly relies on environmental conditions. Here we focus on the spatio-temporal variability of cod recruitment in an effort to detect changes during the critical early life stages. Using International Bottom Trawl Survey (IBTS data from 1974 to 2011, a major spatio-temporal change in the distribution of cod recruits was identified in the late 1990s, characterized by a pronounced decrease in the central and southeastern North Sea stock. Other minor spatial changes were also recorded in the mid-1980s and early 1990s. We tested whether the observed changes in recruits distribution could be related with direct (i.e. temperature and/or indirect (i.e. changes in the quantity and quality of zooplankton prey effects of climate variability. The analyses were based on spatially-resolved time series, i.e. sea surface temperature (SST from the Hadley Center and zooplankton records from the Continuous Plankton Recorder Survey. We showed that spring SST increase was the main driver for the most recent decrease in cod recruitment. The late 1990s were also characterized by relatively low total zooplankton biomass, particularly of energy-rich zooplankton such as the copepod Calanus finmarchicus, which have further contributed to the decline of North Sea cod recruitment. Long-term spatially-resolved observations were used to produce regional distribution models that could further be used to predict the abundance of North Sea cod recruits based on temperature and zooplankton food availability.

SECURE SERVICE DISCOVERY BASED ON PROBE PACKET MECHANISM FOR MANETS

Directory of Open Access Journals (Sweden)

S. Pariselvam

2015-03-01

Full Text Available In MANETs, Service discovery process is always considered to be crucial since they do not possess a centralized infrastructure for communication. Moreover, different services available through the network necessitate varying categories. Hence, a need arises for devising a secure probe based service discovery mechanism to reduce the complexity in providing the services to the network users. In this paper, we propose a Secure Service Discovery Based on Probe Packet Mechanism (SSDPPM for identifying the DoS attack in MANETs, which depicts a new approach for estimating the level of trust present in each and every routing path of a mobile ad hoc network by using probe packets. Probing based service discovery mechanisms mainly identifies a mobile node’s genuineness using a test packet called probe that travels the entire network for the sake of computing the degree of trust maintained between the mobile nodes and it’s attributed impact towards the network performance. The performance of SSDPPM is investigated through a wide range of network related parameters like packet delivery, throughput, Control overhead and total overhead using the version ns-2.26 network simulator. This mechanism SSDPPM, improves the performance of the network in an average by 23% and 19% in terms of packet delivery ratio and throughput than the existing service discovery mechanisms available in the literature.

Temporal binding function of dorsal CA1 is critical for declarative memory formation.

Science.gov (United States)

Sellami, Azza; Al Abed, Alice Shaam; Brayda-Bruno, Laurent; Etchamendy, Nicole; Valério, Stéphane; Oulé, Marie; Pantaléon, Laura; Lamothe, Valérie; Potier, Mylène; Bernard, Katy; Jabourian, Maritza; Herry, Cyril; Mons, Nicole; Piazza, Pier-Vincenzo; Eichenbaum, Howard; Marighetto, Aline

2017-09-19

Temporal binding, the process that enables association between discontiguous stimuli in memory, and relational organization, a process that enables the flexibility of declarative memories, are both hippocampus-dependent and decline in aging. However, how these two processes are related in supporting declarative memory formation and how they are compromised in age-related memory loss remain hypothetical. We here identify a causal link between these two features of declarative memory: Temporal binding is a necessary condition for the relational organization of discontiguous events. We demonstrate that the formation of a relational memory is limited by the capability of temporal binding, which depends on dorsal (d)CA1 activity over time intervals and diminishes in aging. Conversely, relational representation is successful even in aged individuals when the demand on temporal binding is minimized, showing that relational/declarative memory per se is not impaired in aging. Thus, bridging temporal intervals by dCA1 activity is a critical foundation of relational representation, and a deterioration of this mechanism is responsible for the age-associated memory impairment.

PET imaging in temporal lobe epilepsy

International Nuclear Information System (INIS)

Semah, F.

2006-01-01

structural abnormalities outside of the mesial formations were detected in 65% of the cases. Neither the severity of HS nor temporal atrophy appeared related to the topography of hypo-metabolism. However, temporal hypo-metabolism was more extended when temporo-polar signal changes were detected. Among operated patients (n=43), a seizure-free outcome was obtained in 82%. A positive surgical outcome appeared more favorable in the mesial group, however the difference between the 4 groups was not significant. Our results suggest that hypo-metabolism in MTLE may be related to ictal discharge generation and spread pathways, even though structural changes and epilepsy duration may also play a role. The role of the basal ganglia in the control of seizures is suggested by studies in animal models and epileptic patients. It is suggested that circuits of the basal ganglia may control epileptic seizures and that striatal dopaminergic transmission plays a key role in seizure interruption. We first studied patients with ring chromosome 20 (r(20) ) epilepsy which is a very homogenous type of epilepsy and that is clinically characterized by long-lasting seizures suggesting a dysfunction in the seizure control system. The hypothesis that these long-lasting seizures are associated with a reduction of striatal dopamine was addressed in our study. We used [ 18 F]fluoro-L-DOPA PET in 14 patients with r(20) epilepsy. We found that [ 18 F]fluoro-L-DOPA uptake was significantly decreased bilaterally in the putamen and in the caudate nucleus of patients. This reduction was equal for both nuclei and was not correlated with the percentage of cells with r(20) (Biraben, 2004). This study suggested that dysfunction of this neurotransmission may impair the mechanisms which interrupt seizures. This study was followed by a pilot study in patients with MTLE and in patients with the absence of medically refractory seizures to investigate if this abnormality could be related with the ring chromosome 20

PET imaging in temporal lobe epilepsy

Energy Technology Data Exchange (ETDEWEB)

Semah, F. [Service Hospitalier Frederic Joliot, DSV-CEA, 91 Orsay (France)

2006-07-01

structural abnormalities outside of the mesial formations were detected in 65% of the cases. Neither the severity of HS nor temporal atrophy appeared related to the topography of hypo-metabolism. However, temporal hypo-metabolism was more extended when temporo-polar signal changes were detected. Among operated patients (n=43), a seizure-free outcome was obtained in 82%. A positive surgical outcome appeared more favorable in the mesial group, however the difference between the 4 groups was not significant. Our results suggest that hypo-metabolism in MTLE may be related to ictal discharge generation and spread pathways, even though structural changes and epilepsy duration may also play a role. The role of the basal ganglia in the control of seizures is suggested by studies in animal models and epileptic patients. It is suggested that circuits of the basal ganglia may control epileptic seizures and that striatal dopaminergic transmission plays a key role in seizure interruption. We first studied patients with ring chromosome 20 (r(20) ) epilepsy which is a very homogenous type of epilepsy and that is clinically characterized by long-lasting seizures suggesting a dysfunction in the seizure control system. The hypothesis that these long-lasting seizures are associated with a reduction of striatal dopamine was addressed in our study. We used [{sup 18}F]fluoro-L-DOPA PET in 14 patients with r(20) epilepsy. We found that [ {sup 18}F]fluoro-L-DOPA uptake was significantly decreased bilaterally in the putamen and in the caudate nucleus of patients. This reduction was equal for both nuclei and was not correlated with the percentage of cells with r(20) (Biraben, 2004). This study suggested that dysfunction of this neurotransmission may impair the mechanisms which interrupt seizures. This study was followed by a pilot study in patients with MTLE and in patients with the absence of medically refractory seizures to investigate if this abnormality could be related with the ring chromosome

Revealing Significant Relations between Chemical/Biological Features and Activity: Associative Classification Mining for Drug Discovery

Science.gov (United States)

Yu, Pulan

2012-01-01

Classification, clustering and association mining are major tasks of data mining and have been widely used for knowledge discovery. Associative classification mining, the combination of both association rule mining and classification, has emerged as an indispensable way to support decision making and scientific research. In particular, it offers a…

Discovery and Selection of Semantic Web Services

CERN Document Server

Wang, Xia

2013-01-01

For advanced web search engines to be able not only to search for semantically related information dispersed over different web pages, but also for semantic services providing certain functionalities, discovering semantic services is the key issue. Addressing four problems of current solution, this book presents the following contributions. A novel service model independent of semantic service description models is proposed, which clearly defines all elements necessary for service discovery and selection. It takes service selection as its gist and improves efficiency. Corresponding selection algorithms and their implementation as components of the extended Semantically Enabled Service-oriented Architecture in the Web Service Modeling Environment are detailed. Many applications of semantic web services, e.g. discovery, composition and mediation, can benefit from a general approach for building application ontologies. With application ontologies thus built, services are discovered in the same way as with single...

Venomics-Accelerated Cone Snail Venom Peptide Discovery

Science.gov (United States)

Himaya, S. W. A.

2018-01-01

Cone snail venoms are considered a treasure trove of bioactive peptides. Despite over 800 species of cone snails being known, each producing over 1000 venom peptides, only about 150 unique venom peptides are structurally and functionally characterized. To overcome the limitations of the traditional low-throughput bio-discovery approaches, multi-omics systems approaches have been introduced to accelerate venom peptide discovery and characterisation. This “venomic” approach is starting to unravel the full complexity of cone snail venoms and to provide new insights into their biology and evolution. The main challenge for venomics is the effective integration of transcriptomics, proteomics, and pharmacological data and the efficient analysis of big datasets. Novel database search tools and visualisation techniques are now being introduced that facilitate data exploration, with ongoing advances in related omics fields being expected to further enhance venomics studies. Despite these challenges and future opportunities, cone snail venomics has already exponentially expanded the number of novel venom peptide sequences identified from the species investigated, although most novel conotoxins remain to be pharmacologically characterised. Therefore, efficient high-throughput peptide production systems and/or banks of miniaturized discovery assays are required to overcome this bottleneck and thus enhance cone snail venom bioprospecting and accelerate the identification of novel drug leads. PMID:29522462

Venomics-Accelerated Cone Snail Venom Peptide Discovery

Directory of Open Access Journals (Sweden)

S. W. A. Himaya

2018-03-01

Full Text Available Cone snail venoms are considered a treasure trove of bioactive peptides. Despite over 800 species of cone snails being known, each producing over 1000 venom peptides, only about 150 unique venom peptides are structurally and functionally characterized. To overcome the limitations of the traditional low-throughput bio-discovery approaches, multi-omics systems approaches have been introduced to accelerate venom peptide discovery and characterisation. This “venomic” approach is starting to unravel the full complexity of cone snail venoms and to provide new insights into their biology and evolution. The main challenge for venomics is the effective integration of transcriptomics, proteomics, and pharmacological data and the efficient analysis of big datasets. Novel database search tools and visualisation techniques are now being introduced that facilitate data exploration, with ongoing advances in related omics fields being expected to further enhance venomics studies. Despite these challenges and future opportunities, cone snail venomics has already exponentially expanded the number of novel venom peptide sequences identified from the species investigated, although most novel conotoxins remain to be pharmacologically characterised. Therefore, efficient high-throughput peptide production systems and/or banks of miniaturized discovery assays are required to overcome this bottleneck and thus enhance cone snail venom bioprospecting and accelerate the identification of novel drug leads.

Dysphoric mood states are related to sensitivity to temporal changes in contingency

Directory of Open Access Journals (Sweden)

Rachel M. eMsetfi

2012-09-01

Full Text Available A controversial finding in the field of causal learning is that mood contributes to the accuracy of perceptions of uncorrelated relationships. When asked to report the degree of control between an action and its outcome, people with dysphoria or depression are claimed to be more realistic in reporting non-contingency (e.g., Alloy & Abramson, 1979. The strongest evidence for this depressive realism (DR effect is derived from data collected with experimental procedures in which the dependent variables are verbal or written ratings of contingency or cause, and, perhaps more importantly, the independent variable in these procedures may be ambiguous and difficult to define. In order to address these possible confounds, we used a two-response free-operant causal learning task in which the dependent measures were performance based. Participants were required to respond to maximise the occurrence of a temporally contiguous outcome that was programmed with different probabilities, which also varied temporally across two responses. Dysphoric participants were more sensitive to the changing outcome contingencies than controls even though they responded at a similar rate. During probe trials, in which the outcome was masked, their performance recovered more quickly than that of the control group. These data provide unexpected support for the depressive realism hypothesis suggesting that dysphoria is associated with heightened sensitivity to temporal shifts in contingency.

Dysphoric Mood States are Related to Sensitivity to Temporal Changes in Contingency.

Science.gov (United States)

Msetfi, Rachel M; Murphy, Robin A; Kornbrot, Diana E

2012-01-01

A controversial finding in the field of causal learning is that mood contributes to the accuracy of perceptions of uncorrelated relationships. When asked to report the degree of control between an action and its outcome, people with dysphoria or depression are claimed to be more realistic in reporting non-contingency (e.g., Alloy and Abramson, 1979). The strongest evidence for this depressive realism (DR) effect is derived from data collected with experimental procedures in which the dependent variables are verbal or written ratings of contingency or cause, and, perhaps more importantly, the independent variable in these procedures may be ambiguous and difficult to define. In order to address these possible confounds, we used a two-response free-operant causal learning task in which the dependent measures were performance based. Participants were required to respond to maximize the occurrence of a temporally contiguous outcome that was programmed with different probabilities, which also varied temporally across two responses. Dysphoric participants were more sensitive to the changing outcome contingencies than controls even though they responded at a similar rate. During probe trials, in which the outcome was masked, their performance recovered more quickly than that of the control group. These data provide unexpected support for the DR hypothesis suggesting that dysphoria is associated with heightened sensitivity to temporal shifts in contingency.

Aspects of second-order analysis of structured inhomogeneous spatio-temporal processes

DEFF Research Database (Denmark)

Møller, Jesper; Ghorbani, Mohammad

2012-01-01

Statistical methodology for spatio-temporal point processes is in its infancy. We consider second-order analysis based on pair correlation functions and K-functions for general inhomogeneous spatio-temporal point processes and for inhomogeneous spatio-temporal Cox processes. Assuming spatio......-temporal separability of the intensity function, we clarify different meanings of second-order spatio-temporal separability. One is second-order spatio-temporal independence and relates to log-Gaussian Cox processes with an additive covariance structure of the underlying spatio-temporal Gaussian process. Another...... concerns shot-noise Cox processes with a separable spatio-temporal covariance density. We propose diagnostic procedures for checking hypotheses of second-order spatio-temporal separability, which we apply on simulated and real data....

Perspectives on bioanalytical mass spectrometry and automation in drug discovery.

Science.gov (United States)

Janiszewski, John S; Liston, Theodore E; Cole, Mark J

2008-11-01

The use of high speed synthesis technologies has resulted in a steady increase in the number of new chemical entities active in the drug discovery research stream. Large organizations can have thousands of chemical entities in various stages of testing and evaluation across numerous projects on a weekly basis. Qualitative and quantitative measurements made using LC/MS are integrated throughout this process from early stage lead generation through candidate nomination. Nearly all analytical processes and procedures in modern research organizations are automated to some degree. This includes both hardware and software automation. In this review we discuss bioanalytical mass spectrometry and automation as components of the analytical chemistry infrastructure in pharma. Analytical chemists are presented as members of distinct groups with similar skillsets that build automated systems, manage test compounds, assays and reagents, and deliver data to project teams. The ADME-screening process in drug discovery is used as a model to highlight the relationships between analytical tasks in drug discovery. Emerging software and process automation tools are described that can potentially address gaps and link analytical chemistry related tasks. The role of analytical chemists and groups in modern 'industrialized' drug discovery is also discussed.

Discovery of massive neutral vector mesons

International Nuclear Information System (INIS)

Anon.

1976-01-01

Personal accounts of the discovery of massive neutral vector mesons (psi particles) are given by researchers S. Ting, G. Goldhaber, and B. Richter. The double-arm spectrometer and the Cherenkov effect are explained in a technical note, and the solenoidal magnetic detector is discussed in an explanatory note for nonspecialists. Reprints of three papers in Physical Review Letters which announced the discovery of the particles are given: Experimental observation of a heavy particle J, Discovery of a narrow resonance in e + e - annihilation, and Discovery of a second narrow resonance in e + e - annihilation. A discussion of subsequent developments and scientific biographies of the three authors are also presented. 25 figures

Functional principles of registry-based service discovery

NARCIS (Netherlands)

Sundramoorthy, V.; Tan, C.; Hartel, P.H.; Hartog, den J.I.; Scholten, J.

2005-01-01

As Service Discovery Protocols (SDP) are becoming increasingly important for ubiquitous computing, they must behave according to predefined principles. We present the functional Principles of Service Discovery for robust, registry-based service discovery. A methodology to guarantee adherence to

Temporal Coding of Volumetric Imagery

Science.gov (United States)

Llull, Patrick Ryan

of other information within that video; namely, focal and spectral information. The next part of the thesis demonstrates derivative works of CACTI: compressive extended depth of field and compressive spectral-temporal imaging. These works successfully show the technique's extension of temporal coding to improve sensing performance in these other dimensions. Geometrical optics-related tradeoffs, such as the classic challenges of wide-field-of-view and high resolution photography, have motivated the development of mulitscale camera arrays. The advent of such designs less than a decade ago heralds a new era of research- and engineering-related challenges. One significant challenge is that of managing the focal volume (x,y,z ) over wide fields of view and resolutions. The fourth chapter shows advances on focus and image quality assessment for a class of multiscale gigapixel cameras developed at Duke. Along the same line of work, we have explored methods for dynamic and adaptive addressing of focus via point spread function engineering. We demonstrate another form of temporal coding in the form of physical translation of the image plane from its nominal focal position. We demonstrate this technique's capability to generate arbitrary point spread functions.

Materials Discovery | Materials Science | NREL

Science.gov (United States)

Discovery Materials Discovery Images of red and yellow particles NREL's research in materials characterization of sample by incoming beam and measuring outgoing particles, with data being stored and analyzed Staff Scientist Dr. Zakutayev specializes in design of novel semiconductor materials for energy

On the pulse of discovery

Science.gov (United States)

2017-12-01

What started 50 years ago as a `smudge' on paper has flourished into a fundamental field of astrophysics replete with unexpected applications and exciting discoveries. To celebrate the discovery of pulsars, we look at the past, present and future of pulsar astrophysics.

Relational vs. attributive interpretation of nominal compounds differentially engages angular gyrus and anterior temporal lobe.

Science.gov (United States)

Boylan, Christine; Trueswell, John C; Thompson-Schill, Sharon L

2017-06-01

The angular gyrus (AG) and anterior temporal lobe (ATL) have been found to respond to a number of tasks involving combinatorial processing. In this study, we investigate the conceptual combination of nominal compounds, and ask whether ATL/AG activity is modulated by the type of combinatorial operation applied to a nominal compound. We compare relational and attributive interpretations of nominal compounds and find that ATL and AG both discriminate these two types, but in distinct ways. While right AG demonstrated greater positive task-responsive activity for relational compounds, there was a greater negative deflection in the BOLD response in left AG for relational compounds. In left ATL, we found an earlier peak in subjects' BOLD response curves for attributive interpretations. In other words, we observed dissociations in both AG and ATL between relational and attributive nominal compounds, with regard to magnitude in the former and to timing in the latter. These findings expand on prior studies that posit roles for both AG and ATL in conceptual processing generally, and in conceptual combination specifically, by indicating possible functional specializations of these two regions within a larger conceptual knowledge network. Copyright © 2017 Elsevier Inc. All rights reserved.

Auditory temporal processing in patients with temporal lobe epilepsy.

Science.gov (United States)

Lavasani, Azam Navaei; Mohammadkhani, Ghassem; Motamedi, Mahmoud; Karimi, Leyla Jalilvand; Jalaei, Shohreh; Shojaei, Fereshteh Sadat; Danesh, Ali; Azimi, Hadi

2016-07-01

Auditory temporal processing is the main feature of speech processing ability. Patients with temporal lobe epilepsy, despite their normal hearing sensitivity, may present speech recognition disorders. The present study was carried out to evaluate the auditory temporal processing in patients with unilateral TLE. The present study was carried out on 25 patients with epilepsy: 11 patients with right temporal lobe epilepsy and 14 with left temporal lobe epilepsy with a mean age of 31.1years and 18 control participants with a mean age of 29.4years. The two experimental and control groups were evaluated via gap-in-noise and duration pattern sequence tests. One-way ANOVA was run to analyze the data. The mean of the threshold of the GIN test in the control group was observed to be better than that in participants with LTLE and RTLE. Also, it was observed that the percentage of correct responses on the DPS test in the control group and in participants with RTLE was better than that in participants with LTLE. Patients with TLE have difficulties in temporal processing. Difficulties are more significant in patients with LTLE, likely because the left temporal lobe is specialized for the processing of temporal information. Copyright © 2016 Elsevier Inc. All rights reserved.

Fragment-based drug discovery using rational design.

Science.gov (United States)

Jhoti, H

2007-01-01

Fragment-based drug discovery (FBDD) is established as an alternative approach to high-throughput screening for generating novel small molecule drug candidates. In FBDD, relatively small libraries of low molecular weight compounds (or fragments) are screened using sensitive biophysical techniques to detect their binding to the target protein. A lower absolute affinity of binding is expected from fragments, compared to much higher molecular weight hits detected by high-throughput screening, due to their reduced size and complexity. Through the use of iterative cycles of medicinal chemistry, ideally guided by three-dimensional structural data, it is often then relatively straightforward to optimize these weak binding fragment hits into potent and selective lead compounds. As with most other lead discovery methods there are two key components of FBDD; the detection technology and the compound library. In this review I outline the two main approaches used for detecting the binding of low affinity fragments and also some of the key principles that are used to generate a fragment library. In addition, I describe an example of how FBDD has led to the generation of a drug candidate that is now being tested in clinical trials for the treatment of cancer.

The future workforce in cancer prevention: advancing discovery, research, and technology.

Science.gov (United States)

Newhauser, Wayne D; Scheurer, Michael E; Faupel-Badger, Jessica M; Clague, Jessica; Weitzel, Jeffrey; Woods, Kendra V

2012-05-01

As part of a 2-day conference on October 15 and 16, 2009, a nine-member task force composed of scientists, clinicians, educators, administrators, and students from across the USA was formed to discuss research, discovery, and technology obstacles to progress in cancer prevention and control, specifically those related to the cancer prevention workforce. This article summarizes the task force's findings on the current state of the cancer prevention workforce in this area and its needs for the future. The task force identified two types of barriers impeding the current cancer prevention workforce in research, discovery, and technology from reaching its fullest potential: (1) limited cross-disciplinary research opportunities with underutilization of some disciplines is hampering discovery and research in cancer prevention, and (2) new research avenues are not being investigated because technology development and implementation are lagging. Examples of impediments and desired outcomes are provided in each of these areas. Recommended solutions to these problems are based on the goals of enhancing the current cancer prevention workforce and accelerating the pace of discovery and clinical translation.

Discovery of inhibitors of bacterial histidine kinases

NARCIS (Netherlands)

Velikova, N.R.

2014-01-01

Discovery of Inhibitors of Bacterial Histidine Kinases Summary

The thesis is on novel antibacterial drug discovery (http://youtu.be/NRMWOGgeysM). Using structure-based and fragment-based drug discovery approach, we have identified small-molecule histidine-kinase

The temporal-relevance temporal-uncertainty model of prospective duration judgment.

Science.gov (United States)

Zakay, Dan

2015-12-15

A model aimed at explaining prospective duration judgments in real life settings (as well as in the laboratory) is presented. The model is based on the assumption that situational meaning is continuously being extracted by humans' perceptual and cognitive information processing systems. Time is one of the important dimensions of situational meaning. Based on the situational meaning, a value for Temporal Relevance is set. Temporal Relevance reflects the importance of temporal aspects for enabling adaptive behavior in a specific moment in time. When Temporal Relevance is above a certain threshold a prospective duration judgment process is evoked automatically. In addition, a search for relevant temporal information is taking place and its outcomes determine the level of Temporal Uncertainty which reflects the degree of knowledge one has regarding temporal aspects of the task to be performed. The levels of Temporal Relevance and Temporal Uncertainty determine the amount of attentional resources allocated for timing by the executive system. The merit of the model is in connecting timing processes with the ongoing general information processing stream. The model rests on findings in various domains which indicate that cognitive-relevance and self-relevance are powerful determinants of resource allocation policy. The feasibility of the model is demonstrated by analyzing various temporal phenomena. Suggestions for further empirical validation of the model are presented. Copyright © 2015 Elsevier Inc. All rights reserved.

The discovery of X-rays

International Nuclear Information System (INIS)

Farmelo, G.

1995-01-01

This paper relates the discovery of X-rays by Wilhelm Roentgen in november 1895 and the successive experiments carried out by the German searcher to try to identify the origin of the X radiations. Part of his biography is described, his curriculum at the university, his first experiments with cathodic rays, the first human body radiography and the radiography of various materials. In 1901, Roentgen received the first Nobel price just after being promoted to the rank of professor at the University of Munchen. (J.S.). 2 photos

Service discovery using Bloom filters

NARCIS (Netherlands)

Goering, P.T.H.; Heijenk, Geert; Lelieveldt, B.P.F.; Haverkort, Boudewijn R.H.M.; de Laat, C.T.A.M.; Heijnsdijk, J.W.J.

A protocol to perform service discovery in adhoc networks is introduced in this paper. Attenuated Bloom filters are used to distribute services to nodes in the neighborhood and thus enable local service discovery. The protocol has been implemented in a discrete event simulator to investigate the

Temporal Changes in Mortality Related to Extreme Temperatures for 15 Cities in Northeast Asia: Adaptation to Heat and Maladaptation to Cold.

Science.gov (United States)

Chung, Yeonseung; Noh, Heesang; Honda, Yasushi; Hashizume, Masahiro; Bell, Michelle L; Guo, Yue-Liang Leon; Kim, Ho

2017-05-15

Understanding how the temperature-mortality association worldwide changes over time is crucial to addressing questions of human adaptation under climate change. Previous studies investigated the temporal changes in the association over a few discrete time frames or assumed a linear change. Also, most studies focused on attenuation of heat-related mortality and studied the United States or Europe. This research examined continuous temporal changes (potentially nonlinear) in mortality related to extreme temperature (both heat and cold) for 15 cities in Northeast Asia (1972-2009). We used a generalized linear model with splines to simultaneously capture 2 types of nonlinearity: nonlinear association between temperature and mortality and nonlinear change over time in the association. We combined city-specific results to generate country-specific results using Bayesian hierarchical modeling. Cold-related mortality remained roughly constant over decades and slightly increased in the late 2000s, with a larger increase for cardiorespiratory deaths than for deaths from other causes. Heat-related mortality rates have decreased continuously over time, with more substantial decrease in earlier decades, for older populations and for cardiorespiratory deaths. Our findings suggest that future assessment of health effects of climate change should account for the continuous changes in temperature-related health risk and variations by factors such as age, cause of death, and location. © Crown copyright 2017.

Using concepts in literature-based discovery : Simulating Swanson's Raynaud-fish oil and migraine-magnesium discoveries

NARCIS (Netherlands)

Weeber, M; Klein, Henny; de Jong-van den Berg, LTW; Vos, R

Literature-based discovery has resulted in new knowledge. In the biomedical context, Don R. Swanson has generated several literature-based hypotheses that have been corroborated experimentally and clinically. In this paper, we propose a two-step model of the discovery process in which hypotheses are

Cranial base morphology and temporal bone pneumatization in Asian Homo erectus.

Science.gov (United States)

Balzeau, Antoine; Grimaud-Hervé, Dominique

2006-10-01

The external morphological features of the temporal bone are used frequently to determine taxonomic affinities of fossils of the genus Homo. Temporal bone pneumatization has been widely studied in great apes and in early hominids. However, this feature is rarely examined in the later hominids, particularly in Asian Homo erectus. We provide a comparative morphological and quantitative analysis of Asian Homo erectus from the sites of Ngandong, Sambungmacan, and Zhoukoudian, and of Neandertals and anatomically modern Homo sapiens in order to discuss causes and modalities of temporal bone pneumatization during hominid evolution. The evolution of temporal bone pneumatization in the genus Homo is more complex than previously described. Indeed, the Zhoukoudian fossils have a unique pattern of temporal bone pneumatization, whereas Ngandong and Sambungmacan fossils, as well as the Neandertals, more closely resemble the modern human pattern. Moreover, these Chinese fossils are characterized by a wide midvault and a relatively narrow occipital bone. Our results support the point of view that cell development does not play an active role in determining cranial base morphology. Instead, pneumatization is related to available space and to temporal bone morphology, and its development is related to correlated morphology and the relative disposition of the bones and cerebral lobes. Because variation in pneumatization is extensive within the same species, the phyletic implications of pneumatization are limited in the taxa considered here.

12 CFR 747.24 - Scope of document discovery.

Science.gov (United States)

2010-01-01

... act of Congress, or the principles of common law provide. (d) Time limits. All discovery, including... 12 Banks and Banking 6 2010-01-01 2010-01-01 false Scope of document discovery. 747.24 Section 747... of Practice and Procedure § 747.24 Scope of document discovery. (a) Limits on discovery. (1) Subject...

Conscious and nonconscious memory effects are temporally dissociable.

Science.gov (United States)

Slotnick, Scott D; Schacter, Daniel L

2010-03-01

Intentional (explicit) retrieval can reactivate sensory cortex, which is widely assumed to reflect conscious processing. In the present study, we used an explicit visual memory event-related potential paradigm to investigate whether such retrieval related sensory activity could be separated into conscious and nonconscious components. During study, abstract shapes were presented in the left or right visual field. During test, old and new shapes were presented centrally and participants classified each shape as "old-left", "old-right", or "new". Conscious activity was isolated by comparing accurate memory for shape and location (old-hits) with forgotten shapes (old-misses), and nonconscious activity was isolated by comparing old-left-misses with old-right-misses and vice versa. Conscious visual sensory activity had a late temporal onset (after 800 ms) while nonconscious visual sensory activity had an early temporal onset (before 800 ms). These results suggest explicit memory related sensory activity reflects both conscious and nonconscious processes that are temporally dissociable.

Resource Discovery in Activity-Based Sensor Networks

DEFF Research Database (Denmark)

Bucur, Doina; Bardram, Jakob

This paper proposes a service discovery protocol for sensor networks that is specifically tailored for use in humancentered pervasive environments. It uses the high-level concept of computational activities (as logical bundles of data and resources) to give sensors in Activity-Based Sensor Networ....... ABSN enhances the generic Extended Zone Routing Protocol with logical sensor grouping and greatly lowers network overhead during the process of discovery, while keeping discovery latency close to optimal.......This paper proposes a service discovery protocol for sensor networks that is specifically tailored for use in humancentered pervasive environments. It uses the high-level concept of computational activities (as logical bundles of data and resources) to give sensors in Activity-Based Sensor Networks...... (ABSNs) knowledge about their usage even at the network layer. ABSN redesigns classical network-level service discovery protocols to include and use this logical structuring of the network for a more practically applicable service discovery scheme. Noting that in practical settings activity-based sensor...

The shifting temporalities of online news

DEFF Research Database (Denmark)

Bødker, Henrik; Brügger, Niels

2018-01-01

websites (as well as other characteristics of online archives), the construction of the empirical base stands in a complex relation to the analytical framework applied. As much as the article is a historical analysis of the temporality of online news, it, thus, also offers a range of methodological......As much as news websites news can be characterised by speed and immediacy, they are also recognisable online periodicals, which accumulate preceding news items. This is, as with the constitution of time in general, linked to relations between change and continuity. This article aims to understand...... consequently employs a framework for webpage analysis that primarily focuses on the syntactical level where temporalities emerge as relations between textual elements that change at very different intervals. This framework is applied to examples from the different stages of The Guardian’s webpage from 1996...

[Spatio-temporal distribution of scrub typhus and related influencing factors in coastal beach area of Yancheng, China].

Science.gov (United States)

Chen, Y Z; Li, F; Xu, H; Huang, L C; Gu, Z G; Sun, Z Y; Yan, G J; Zhu, Y J; Tang, C

2016-02-01

In order to provide better programs on monitoring, early warning and prevention of Scrub Typhus in the coastal beach area, temporal-spatial distribution characteristics of scrub typhus were summarized. Relationships between temporal-spatial clustering of Scrub Typhus, meteorological factors, rodent distribution and the biological characteristics in coastal beach area of Yancheng city, were studied. Reports on network-based Scrub Typhus epidemics and information on population, weather situation through monitoring those stations, from 2005 to 2014 were collected and processed, in the coastal beach area of Yancheng city. Distribution, density of the population concerned and seasonal fluctuation on rodents were monitored in coastal beach area, from April 2011 to December, 2013. METHODS as descriptive statistics, space-time permutation scantistics, autocorrelation and Cross-correlation analysis etc, were used to analyze the temporal-spatial distribution of Scrub Typhus and correlation with rodent distribution, density fluctuation and meteorological indexes. Zero-inflated Pearson (ZIP) regression model was contributed according to the distribution of related data. All methods were calculated under Excel 2003, SPSS 16.0, Mapinfo 11.0, Satscan 9.0 and Stata/SE 10.0 softwares. (1) The incidence of Scrub Typhus was gradually increasing and the highest incidence of the year was seen in 2014, as 5.81/10 million. There was an autumn peak of Scrub typhus, with the highest incidence rate as 12.02/10 million in November. The incidence rate of Scrub typhus appeared high in Binhai, Dafeng and Xiangshui, with the average incidence rates appeared as 3.30/10 million, 3.21/10 million and 2.79/10 million, respectively. There were 12 towns with high incidence rates in the coastal beach area, with incidence rate showed between 4.41/10 and 10.03/10 million. (2) There were three incidence clusters of Scrub typhus seen in 25 towns, between October 2012 and November 2012 in Dongtai, Dafeng

Stem cell technology for drug discovery and development.

Science.gov (United States)

Hook, Lilian A

2012-04-01

Stem cells have enormous potential to revolutionise the drug discovery process at all stages, from target identification through to toxicology studies. Their ability to generate physiologically relevant cells in limitless supply makes them an attractive alternative to currently used recombinant cell lines or primary cells. However, realisation of the full potential of stem cells is currently hampered by the difficulty in routinely directing stem cell differentiation to reproducibly and cost effectively generate pure populations of specific cell types. In this article we discuss how stem cells have already been used in the drug discovery process and how novel technologies, particularly in relation to stem cell differentiation, can be applied to attain widespread adoption of stem cell technology by the pharmaceutical industry. Copyright © 2011 Elsevier Ltd. All rights reserved.

Price discovery in a continuous-time setting

DEFF Research Database (Denmark)

Dias, Gustavo Fruet; Fernandes, Marcelo; Scherrer, Cristina

We formulate a continuous-time price discovery model in which the price discovery measure varies (stochastically) at daily frequency. We estimate daily measures of price discovery using a kernel-based OLS estimator instead of running separate daily VECM regressions as standard in the literature. We...... show that our estimator is not only consistent, but also outperforms the standard daily VECM in finite samples. We illustrate our theoretical findings by studying the price discovery process of 10 actively traded stocks in the U.S. from 2007 to 2013....

The Spatial and Temporal Layers of Global History

DEFF Research Database (Denmark)

Schulz-Forberg, Hagen

2013-01-01

Recent debates on global history have challenged the understanding of history beyond the nation-state. Simultaneously, they search for non-Eurocentric approaches. This has repercussions on the relation between historical space and time in both historical interpretation and in research design....... This article reflects on the possibilities of a global conceptual history by expanding Reinhart Koselleck’s theory of temporal layers (Zeitschichten) into global spaces. To this end, it introduces the notion of spatial layers (Raumschichten). First, historicisation and its relation to and interaction...... with spatialisation and temporalisation is pondered; then, the impact of global spatial and temporal complexities on comparative and conceptual history is considered, before, thirdly, a framework of three tensions of global history – normative, temporal and spatial – is introduced as a way to concretely unfold...

Defining Creativity with Discovery

OpenAIRE

Wilson, Nicholas Charles; Martin, Lee

2017-01-01

The standard definition of creativity has enabled significant empirical and theoretical advances, yet contains philosophical conundrums concerning the nature of novelty and the role of recognition and values. In this work we offer an act of conceptual valeting that addresses these issues and in doing so, argue that creativity definitions can be extended through the use of discovery. Drawing on dispositional realist philosophy we outline why adding the discovery and bringing into being of new ...

On the antiproton discovery

International Nuclear Information System (INIS)

Piccioni, O.

1989-01-01

The author of this article describes his own role in the discovery of the antiproton. Although Segre and Chamberlain received the Nobel Prize in 1959 for its discovery, the author claims that their experimental method was his idea which he communicated to them informally in December 1954. He describes how his application for citizenship (he was Italian), and other scientists' manipulation, prevented him from being at Berkeley to work on the experiment himself. (UK)

43 CFR 4.826 - Discovery.

Science.gov (United States)

2010-10-01

... Review Under Part 17 of This Title-Nondiscrimination in Federally Assisted Programs of the Department of... the person from whom discovery is sought, and for good cause shown, the administrative law judge may make any order which justice requires to limit or condition discovery in order to protect a party or...

Melodic pattern discovery by structural analysis via wavelets and clustering techniques

DEFF Research Database (Denmark)

Velarde, Gissel; Meredith, David

We present an automatic method to support melodic pattern discovery by structural analysis of symbolic representations by means of wavelet analysis and clustering techniques. In previous work, we used the method to recognize the parent works of melodic segments, or to classify tunes into tune......-means to cluster melodic segments into groups of measured similarity and obtain a raking of the most prototypical melodic segments or patterns and their occurrences. We test the method on the JKU Patterns Development Database and evaluate it based on the ground truth defined by the MIREX 2013 Discovery of Repeated...... Themes & Sections task. We compare the results of our method to the output of geometric approaches. Finally, we discuss about the relevance of our wavelet-based analysis in relation to structure, pattern discovery, similarity and variation, and comment about the considerations of the method when used...

Temporal ecology in the Anthropocene.

Science.gov (United States)

Wolkovich, E M; Cook, B I; McLauchlan, K K; Davies, T J

2014-11-01

Two fundamental axes - space and time - shape ecological systems. Over the last 30 years spatial ecology has developed as an integrative, multidisciplinary science that has improved our understanding of the ecological consequences of habitat fragmentation and loss. We argue that accelerating climate change - the effective manipulation of time by humans - has generated a current need to build an equivalent framework for temporal ecology. Climate change has at once pressed ecologists to understand and predict ecological dynamics in non-stationary environments, while also challenged fundamental assumptions of many concepts, models and approaches. However, similarities between space and time, especially related issues of scaling, provide an outline for improving ecological models and forecasting of temporal dynamics, while the unique attributes of time, particularly its emphasis on events and its singular direction, highlight where new approaches are needed. We emphasise how a renewed, interdisciplinary focus on time would coalesce related concepts, help develop new theories and methods and guide further data collection. The next challenge will be to unite predictive frameworks from spatial and temporal ecology to build robust forecasts of when and where environmental change will pose the largest threats to species and ecosystems, as well as identifying the best opportunities for conservation. © 2014 John Wiley & Sons Ltd/CNRS.

Resource-estimation models and predicted discovery

International Nuclear Information System (INIS)

Hill, G.W.

1982-01-01

Resources have been estimated by predictive extrapolation from past discovery experience, by analogy with better explored regions, or by inference from evidence of depletion of targets for exploration. Changes in technology and new insights into geological mechanisms have occurred sufficiently often in the long run to form part of the pattern of mature discovery experience. The criterion, that a meaningful resource estimate needs an objective measure of its precision or degree of uncertainty, excludes 'estimates' based solely on expert opinion. This is illustrated by development of error measures for several persuasive models of discovery and production of oil and gas in USA, both annually and in terms of increasing exploration effort. Appropriate generalizations of the models resolve many points of controversy. This is illustrated using two USA data sets describing discovery of oil and of U 3 O 8 ; the latter set highlights an inadequacy of available official data. Review of the oil-discovery data set provides a warrant for adjusting the time-series prediction to a higher resource figure for USA petroleum. (author)

Automated discovery systems and the inductivist controversy

Science.gov (United States)

Giza, Piotr

2017-09-01

The paper explores possible influences that some developments in the field of branches of AI, called automated discovery and machine learning systems, might have upon some aspects of the old debate between Francis Bacon's inductivism and Karl Popper's falsificationism. Donald Gillies facetiously calls this controversy 'the duel of two English knights', and claims, after some analysis of historical cases of discovery, that Baconian induction had been used in science very rarely, or not at all, although he argues that the situation has changed with the advent of machine learning systems. (Some clarification of terms machine learning and automated discovery is required here. The key idea of machine learning is that, given data with associated outcomes, software can be trained to make those associations in future cases which typically amounts to inducing some rules from individual cases classified by the experts. Automated discovery (also called machine discovery) deals with uncovering new knowledge that is valuable for human beings, and its key idea is that discovery is like other intellectual tasks and that the general idea of heuristic search in problem spaces applies also to discovery tasks. However, since machine learning systems discover (very low-level) regularities in data, throughout this paper I use the generic term automated discovery for both kinds of systems. I will elaborate on this later on). Gillies's line of argument can be generalised: thanks to automated discovery systems, philosophers of science have at their disposal a new tool for empirically testing their philosophical hypotheses. Accordingly, in the paper, I will address the question, which of the two philosophical conceptions of scientific method is better vindicated in view of the successes and failures of systems developed within three major research programmes in the field: machine learning systems in the Turing tradition, normative theory of scientific discovery formulated by Herbert Simon

7 CFR 283.28 - Discovery.

Science.gov (United States)

2010-01-01

... 7 Agriculture 4 2010-01-01 2010-01-01 false Discovery. 283.28 Section 283.28 Agriculture Regulations of the Department of Agriculture (Continued) FOOD AND NUTRITION SERVICE, DEPARTMENT OF AGRICULTURE... Appeals of QC Claims of Less Than $50,000 § 283.28 Discovery. Upon motion and as ordered by the ALJ...

GRASS GIS: The first Open Source Temporal GIS

Science.gov (United States)

Gebbert, Sören; Leppelt, Thomas

2015-04-01

GRASS GIS is a full featured, general purpose Open Source geographic information system (GIS) with raster, 3D raster and vector processing support[1]. Recently, time was introduced as a new dimension that transformed GRASS GIS into the first Open Source temporal GIS with comprehensive spatio-temporal analysis, processing and visualization capabilities[2]. New spatio-temporal data types were introduced in GRASS GIS version 7, to manage raster, 3D raster and vector time series. These new data types are called space time datasets. They are designed to efficiently handle hundreds of thousands of time stamped raster, 3D raster and vector map layers of any size. Time stamps can be defined as time intervals or time instances in Gregorian calendar time or relative time. Space time datasets are simplifying the processing and analysis of large time series in GRASS GIS, since these new data types are used as input and output parameter in temporal modules. The handling of space time datasets is therefore equal to the handling of raster, 3D raster and vector map layers in GRASS GIS. A new dedicated Python library, the GRASS GIS Temporal Framework, was designed to implement the spatio-temporal data types and their management. The framework provides the functionality to efficiently handle hundreds of thousands of time stamped map layers and their spatio-temporal topological relations. The framework supports reasoning based on the temporal granularity of space time datasets as well as their temporal topology. It was designed in conjunction with the PyGRASS [3] library to support parallel processing of large datasets, that has a long tradition in GRASS GIS [4,5]. We will present a subset of more than 40 temporal modules that were implemented based on the GRASS GIS Temporal Framework, PyGRASS and the GRASS GIS Python scripting library. These modules provide a comprehensive temporal GIS tool set. The functionality range from space time dataset and time stamped map layer management

Discovery of charm

International Nuclear Information System (INIS)

Goldhaber, G.

1984-11-01

In my talk I will cover the period 1973 to 1976 which saw the discoveries of the J/psi and psi' resonances and most of the Psion spectroscopy, the tau lepton and the D 0 ,D + charmed meson doublet. Occasionally I will refer briefly to more recent results. Since this conference is on the history of the weak-interactions I will deal primarily with the properties of naked charm and in particular the weakly decaying doublet of charmed mesons. Most of the discoveries I will mention were made with the SLAC-LBL Magnetic Detector or MARK I which we operated at SPEAR from 1973 to 1976. 27 references

Data mining-aided materials discovery and optimization

Directory of Open Access Journals (Sweden)

Wencong Lu

2017-09-01

Full Text Available Recent developments in data mining-aided materials discovery and optimization are reviewed in this paper, and an introduction to the materials data mining (MDM process is provided using case studies. Both qualitative and quantitative methods in machine learning can be adopted in the MDM process to accomplish different tasks in materials discovery, design, and optimization. State-of-the-art techniques in data mining-aided materials discovery and optimization are demonstrated by reviewing the controllable synthesis of dendritic Co3O4 superstructures, materials design of layered double hydroxide, battery materials discovery, and thermoelectric materials design. The results of the case studies indicate that MDM is a powerful approach for use in materials discovery and innovation, and will play an important role in the development of the Materials Genome Initiative and Materials Informatics.

Temporal plus epilepsy is a major determinant of temporal lobe surgery failures.

Science.gov (United States)

Barba, Carmen; Rheims, Sylvain; Minotti, Lorella; Guénot, Marc; Hoffmann, Dominique; Chabardès, Stephan; Isnard, Jean; Kahane, Philippe; Ryvlin, Philippe

2016-02-01

Reasons for failed temporal lobe epilepsy surgery remain unclear. Temporal plus epilepsy, characterized by a primary temporal lobe epileptogenic zone extending to neighboured regions, might account for a yet unknown proportion of these failures. In this study all patients from two epilepsy surgery programmes who fulfilled the following criteria were included: (i) operated from an anterior temporal lobectomy or disconnection between January 1990 and December 2001; (ii) magnetic resonance imaging normal or showing signs of hippocampal sclerosis; and (iii) postoperative follow-up ≥ 24 months for seizure-free patients. Patients were classified as suffering from unilateral temporal lobe epilepsy, bitemporal epilepsy or temporal plus epilepsy based on available presurgical data. Kaplan-Meier survival analysis was used to calculate the probability of seizure freedom over time. Predictors of seizure recurrence were investigated using Cox proportional hazards model. Of 168 patients included, 108 (63.7%) underwent stereoelectroencephalography, 131 (78%) had hippocampal sclerosis, 149 suffered from unilateral temporal lobe epilepsy (88.7%), one from bitemporal epilepsy (0.6%) and 18 (10.7%) from temporal plus epilepsy. The probability of Engel class I outcome at 10 years of follow-up was 67.3% (95% CI: 63.4-71.2) for the entire cohort, 74.5% (95% CI: 70.6-78.4) for unilateral temporal lobe epilepsy, and 14.8% (95% CI: 5.9-23.7) for temporal plus epilepsy. Multivariate analyses demonstrated four predictors of seizure relapse: temporal plus epilepsy (P temporal lobe surgery failure was 5.06 (95% CI: 2.36-10.382) greater in patients with temporal plus epilepsy than in those with unilateral temporal lobe epilepsy. Temporal plus epilepsy represents a hitherto unrecognized prominent cause of temporal lobe surgery failures. In patients with temporal plus epilepsy, anterior temporal lobectomy appears very unlikely to control seizures and should not be advised. Whether larger

Scientific Discoveries: What Is Required for Lasting Impact.

Science.gov (United States)

Lømo, Terje

2016-01-01

I have been involved in two scientific discoveries of some impact. One is the discovery of long-term potentiation (LTP), the phenomenon that brief, high-frequency impulse activity at synapses in the brain can lead to long-lasting increases in their efficiency of transmission. This finding demonstrated that synapses are plastic, a property thought to be necessary for learning and memory. The other discovery is that nerve-evoked muscle impulse activity, rather than putative trophic factors, controls the properties of muscle fibers. Here I describe how these two discoveries were made, the unexpected difficulties of reproducing the first discovery, and the controversies that followed the second discovery. I discuss why the first discovery took many years to become generally recognized, whereas the second caused an immediate sensation and entered textbooks and major reviews but is now largely forgotten. In the long run, discovering a new phenomenon has greater impact than falsifying a popular hypothesis.

A Temporal Extension to Traditional Empirical Orthogonal Function Analysis

DEFF Research Database (Denmark)

Nielsen, Allan Aasbjerg; Hilger, Klaus Baggesen; Andersen, Ole Baltazar

2002-01-01

(EOF) analysis, which provides a non-temporal analysis of one variable over time. The temporal extension proves its strength in separating the signals at different periods in an analysis of relevant oceanographic properties related to one of the largest El Niño events ever recorded....

12 CFR 509.102 - Discovery.

Science.gov (United States)

2010-01-01

... 12 Banks and Banking 5 2010-01-01 2010-01-01 false Discovery. 509.102 Section 509.102 Banks and Banking OFFICE OF THRIFT SUPERVISION, DEPARTMENT OF THE TREASURY RULES OF PRACTICE AND PROCEDURE IN ADJUDICATORY PROCEEDINGS Local Rules § 509.102 Discovery. (a) In general. A party may take the deposition of an...

Modeling spatial-temporal operations with context-dependent associative memories.

Science.gov (United States)

Mizraji, Eduardo; Lin, Juan

2015-10-01

We organize our behavior and store structured information with many procedures that require the coding of spatial and temporal order in specific neural modules. In the simplest cases, spatial and temporal relations are condensed in prepositions like "below" and "above", "behind" and "in front of", or "before" and "after", etc. Neural operators lie beneath these words, sharing some similarities with logical gates that compute spatial and temporal asymmetric relations. We show how these operators can be modeled by means of neural matrix memories acting on Kronecker tensor products of vectors. The complexity of these memories is further enhanced by their ability to store episodes unfolding in space and time. How does the brain scale up from the raw plasticity of contingent episodic memories to the apparent stable connectivity of large neural networks? We clarify this transition by analyzing a model that flexibly codes episodic spatial and temporal structures into contextual markers capable of linking different memory modules.

Temporal compression in episodic memory for real-life events.

Science.gov (United States)

Jeunehomme, Olivier; Folville, Adrien; Stawarczyk, David; Van der Linden, Martial; D'Argembeau, Arnaud

2018-07-01

Remembering an event typically takes less time than experiencing it, suggesting that episodic memory represents past experience in a temporally compressed way. Little is known, however, about how the continuous flow of real-life events is summarised in memory. Here we investigated the nature and determinants of temporal compression by directly comparing memory contents with the objective timing of events as measured by a wearable camera. We found that episodic memories consist of a succession of moments of prior experience that represent events with varying compression rates, such that the density of retrieved information is modulated by goal processing and perceptual changes. Furthermore, the results showed that temporal compression rates remain relatively stable over one week and increase after a one-month delay, particularly for goal-related events. These data shed new light on temporal compression in episodic memory and suggest that compression rates are adaptively modulated to maintain current goal-relevant information.

Maximum Entropy in Drug Discovery

Directory of Open Access Journals (Sweden)

Chih-Yuan Tseng

2014-07-01

Full Text Available Drug discovery applies multidisciplinary approaches either experimentally, computationally or both ways to identify lead compounds to treat various diseases. While conventional approaches have yielded many US Food and Drug Administration (FDA-approved drugs, researchers continue investigating and designing better approaches to increase the success rate in the discovery process. In this article, we provide an overview of the current strategies and point out where and how the method of maximum entropy has been introduced in this area. The maximum entropy principle has its root in thermodynamics, yet since Jaynes’ pioneering work in the 1950s, the maximum entropy principle has not only been used as a physics law, but also as a reasoning tool that allows us to process information in hand with the least bias. Its applicability in various disciplines has been abundantly demonstrated. We give several examples of applications of maximum entropy in different stages of drug discovery. Finally, we discuss a promising new direction in drug discovery that is likely to hinge on the ways of utilizing maximum entropy.

Temporal Context, Preference, and Resistance to Change

Science.gov (United States)

Podlesnik, Christopher A.; Jimenez-Gomez, Corina; Thrailkill, Eric A.; Shahan, Timothy A.

2011-01-01

According to behavioral momentum theory, preference and relative resistance to change in concurrent chains schedules are correlated and reflect the relative conditioned value of discriminative stimuli. In the present study, we explore the generality of this relation by manipulating the temporal context within a concurrent-chains procedure through…

Deep Learning in Drug Discovery.

Science.gov (United States)

Gawehn, Erik; Hiss, Jan A; Schneider, Gisbert

2016-01-01

Artificial neural networks had their first heyday in molecular informatics and drug discovery approximately two decades ago. Currently, we are witnessing renewed interest in adapting advanced neural network architectures for pharmaceutical research by borrowing from the field of "deep learning". Compared with some of the other life sciences, their application in drug discovery is still limited. Here, we provide an overview of this emerging field of molecular informatics, present the basic concepts of prominent deep learning methods and offer motivation to explore these techniques for their usefulness in computer-assisted drug discovery and design. We specifically emphasize deep neural networks, restricted Boltzmann machine networks and convolutional networks. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Bioinformatics in translational drug discovery.

Science.gov (United States)

Wooller, Sarah K; Benstead-Hume, Graeme; Chen, Xiangrong; Ali, Yusuf; Pearl, Frances M G

2017-08-31

Bioinformatics approaches are becoming ever more essential in translational drug discovery both in academia and within the pharmaceutical industry. Computational exploitation of the increasing volumes of data generated during all phases of drug discovery is enabling key challenges of the process to be addressed. Here, we highlight some of the areas in which bioinformatics resources and methods are being developed to support the drug discovery pipeline. These include the creation of large data warehouses, bioinformatics algorithms to analyse 'big data' that identify novel drug targets and/or biomarkers, programs to assess the tractability of targets, and prediction of repositioning opportunities that use licensed drugs to treat additional indications. © 2017 The Author(s).

Evolution of bayesian-related research over time: a temporal text mining task

CSIR Research Space (South Africa)

de Waal, A

2006-06-01

Full Text Available Ronald Reagan’s Radio Addresses? Bayesian Analysis 2006, Volume 1, Number 2, pp. 189-383. 2. Mei Q and Zhai C, 2005. Discovering Evolutionary Theme Patterns from Text – An Exploration of Temporal Text Mining. KDD’05, August 21-24, 2005. Chicago...

The Discovery of the Social Life of Swedish Schoolchildren

Science.gov (United States)

Larsson, Anna

2012-01-01

This article demonstrates the "discovery of the social life of schoolchildren" by showing how an interest for children's peer relations emerged in a Swedish educational and medial context. Drawing on historical and sociological childhood studies, the article analyses the concept of schoolchildren's social life in the 1950s, 1960s and…

Data Science and Optimal Learning for Material Discovery and Design

Science.gov (United States)

; Optimal Learning for Material Discovery & Design Data Science and Optimal Learning for Material inference and optimization methods that can constrain predictions using insights and results from theory directions in the application of information theoretic tools to materials problems related to learning from

What Is Spatio-Temporal Data Warehousing?

Science.gov (United States)

Vaisman, Alejandro; Zimányi, Esteban

In the last years, extending OLAP (On-Line Analytical Processing) systems with spatial and temporal features has attracted the attention of the GIS (Geographic Information Systems) and database communities. However, there is no a commonly agreed definition of what is a spatio-temporal data warehouse and what functionality such a data warehouse should support. Further, the solutions proposed in the literature vary considerably in the kind of data that can be represented as well as the kind of queries that can be expressed. In this paper we present a conceptual framework for defining spatio-temporal data warehouses using an extensible data type system. We also define a taxonomy of different classes of queries of increasing expressive power, and show how to express such queries using an extension of the tuple relational calculus with aggregated functions.

Electrocorticographic Temporal Alteration Mapping: A Clinical Technique for Mapping the Motor Cortex with Movement-Related Cortical Potentials

Directory of Open Access Journals (Sweden)

Zehan Wu

2017-06-01

Full Text Available We propose electrocorticographic temporal alteration mapping (ETAM for motor cortex mapping by utilizing movement-related cortical potentials (MRCPs within the low-frequency band [0.05-3] Hz. This MRCP waveform-based temporal domain approach was compared with the state-of-the-art electrocorticographic frequency alteration mapping (EFAM, which is based on frequency spectrum dynamics. Five patients (two epilepsy cases and three tumor cases were enrolled in the study. Each patient underwent intraoperative direct electrocortical stimulation (DECS procedure for motor cortex localization. Moreover, the patients were required to perform simple brisk wrist extension task during awake craniotomy surgery. Cross-validation results showed that the proposed ETAM method had high sensitivity (81.8% and specificity (94.3% in identifying sites which exhibited positive DECS motor responses. Moreover, although the sensitivity of the ETAM and EFAM approaches was not significantly different, ETAM had greater specificity compared with EFAM (94.3 vs. 86.1%. These results indicate that for the intraoperative functional brain mapping, ETAM is a promising novel approach for motor cortex localization with the potential to reduce the need for cortical electrical stimulation.

Functional Brain Connectome and Its Relation to Hoehn and Yahr Stage in Parkinson Disease.

Science.gov (United States)

Suo, Xueling; Lei, Du; Li, Nannan; Cheng, Lan; Chen, Fuqin; Wang, Meiyun; Kemp, Graham J; Peng, Rong; Gong, Qiyong

2017-12-01

Purpose To use resting-state functional magnetic resonance (MR) imaging and graph theory approaches to investigate the brain functional connectome and its potential relation to disease severity in Parkinson disease (PD). Materials and Methods This case-control study was approved by the local research ethics committee, and all participants provided informed consent. There were 153 right-handed patients with PD and 81 healthy control participants recruited who were matched for age, sex, and handedness to undergo a 3-T resting-state functional MR examination. The whole-brain functional connectome was constructed by thresholding the Pearson correlation matrices of 90 brain regions, and the topologic properties were analyzed by using graph theory approaches. Nonparametric permutation tests were used to compare topologic properties, and their relationship to disease severity was assessed. Results The functional connectome in PD showed abnormalities at the global level (ie, decrease in clustering coefficient, global efficiency, and local efficiency, and increase in characteristic path length) and at the nodal level (decreased nodal centralities in the sensorimotor cortex, default mode, and temporal-occipital regions; P left postcentral gyrus and left superior temporal gyrus correlated negatively with Unified Parkinson's Disease Rating Scale III score (P = .038, false discovery rate corrected, r = -0.198; and P = .009, false discovery rate corrected, r = -0.270, respectively) and decreased with increasing Hoehn and Yahr stage in patients with PD. Conclusion The configurations of brain functional connectome in patients with PD were perturbed and correlated with disease severity, notably with those responsible for motor functions. These results provide topologic insights into understanding the neural functional changes in relation to disease severity of PD. © RSNA, 2017 Online supplemental material is available for this article. An earlier incorrect version of this article

Mining manufacturing data for discovery of high productivity process characteristics.

Science.gov (United States)

Charaniya, Salim; Le, Huong; Rangwala, Huzefa; Mills, Keri; Johnson, Kevin; Karypis, George; Hu, Wei-Shou

2010-06-01

Modern manufacturing facilities for bioproducts are highly automated with advanced process monitoring and data archiving systems. The time dynamics of hundreds of process parameters and outcome variables over a large number of production runs are archived in the data warehouse. This vast amount of data is a vital resource to comprehend the complex characteristics of bioprocesses and enhance production robustness. Cell culture process data from 108 'trains' comprising production as well as inoculum bioreactors from Genentech's manufacturing facility were investigated. Each run constitutes over one-hundred on-line and off-line temporal parameters. A kernel-based approach combined with a maximum margin-based support vector regression algorithm was used to integrate all the process parameters and develop predictive models for a key cell culture performance parameter. The model was also used to identify and rank process parameters according to their relevance in predicting process outcome. Evaluation of cell culture stage-specific models indicates that production performance can be reliably predicted days prior to harvest. Strong associations between several temporal parameters at various manufacturing stages and final process outcome were uncovered. This model-based data mining represents an important step forward in establishing a process data-driven knowledge discovery in bioprocesses. Implementation of this methodology on the manufacturing floor can facilitate a real-time decision making process and thereby improve the robustness of large scale bioprocesses. 2010 Elsevier B.V. All rights reserved.

Natural Products for Drug Discovery in the 21st Century: Innovations for Novel Drug Discovery

Directory of Open Access Journals (Sweden)

Nicholas Ekow Thomford

2018-05-01

Full Text Available The therapeutic properties of plants have been recognised since time immemorial. Many pathological conditions have been treated using plant-derived medicines. These medicines are used as concoctions or concentrated plant extracts without isolation of active compounds. Modern medicine however, requires the isolation and purification of one or two active compounds. There are however a lot of global health challenges with diseases such as cancer, degenerative diseases, HIV/AIDS and diabetes, of which modern medicine is struggling to provide cures. Many times the isolation of “active compound” has made the compound ineffective. Drug discovery is a multidimensional problem requiring several parameters of both natural and synthetic compounds such as safety, pharmacokinetics and efficacy to be evaluated during drug candidate selection. The advent of latest technologies that enhance drug design hypotheses such as Artificial Intelligence, the use of ‘organ-on chip’ and microfluidics technologies, means that automation has become part of drug discovery. This has resulted in increased speed in drug discovery and evaluation of the safety, pharmacokinetics and efficacy of candidate compounds whilst allowing novel ways of drug design and synthesis based on natural compounds. Recent advances in analytical and computational techniques have opened new avenues to process complex natural products and to use their structures to derive new and innovative drugs. Indeed, we are in the era of computational molecular design, as applied to natural products. Predictive computational softwares have contributed to the discovery of molecular targets of natural products and their derivatives. In future the use of quantum computing, computational softwares and databases in modelling molecular interactions and predicting features and parameters needed for drug development, such as pharmacokinetic and pharmacodynamics, will result in few false positive leads in drug

Natural Products for Drug Discovery in the 21st Century: Innovations for Novel Drug Discovery.

Science.gov (United States)

Thomford, Nicholas Ekow; Senthebane, Dimakatso Alice; Rowe, Arielle; Munro, Daniella; Seele, Palesa; Maroyi, Alfred; Dzobo, Kevin

2018-05-25

The therapeutic properties of plants have been recognised since time immemorial. Many pathological conditions have been treated using plant-derived medicines. These medicines are used as concoctions or concentrated plant extracts without isolation of active compounds. Modern medicine however, requires the isolation and purification of one or two active compounds. There are however a lot of global health challenges with diseases such as cancer, degenerative diseases, HIV/AIDS and diabetes, of which modern medicine is struggling to provide cures. Many times the isolation of "active compound" has made the compound ineffective. Drug discovery is a multidimensional problem requiring several parameters of both natural and synthetic compounds such as safety, pharmacokinetics and efficacy to be evaluated during drug candidate selection. The advent of latest technologies that enhance drug design hypotheses such as Artificial Intelligence, the use of 'organ-on chip' and microfluidics technologies, means that automation has become part of drug discovery. This has resulted in increased speed in drug discovery and evaluation of the safety, pharmacokinetics and efficacy of candidate compounds whilst allowing novel ways of drug design and synthesis based on natural compounds. Recent advances in analytical and computational techniques have opened new avenues to process complex natural products and to use their structures to derive new and innovative drugs. Indeed, we are in the era of computational molecular design, as applied to natural products. Predictive computational softwares have contributed to the discovery of molecular targets of natural products and their derivatives. In future the use of quantum computing, computational softwares and databases in modelling molecular interactions and predicting features and parameters needed for drug development, such as pharmacokinetic and pharmacodynamics, will result in few false positive leads in drug development. This review

Behavioral sensitivity of temporally modulated striatal neurons

Directory of Open Access Journals (Sweden)

George ePortugal

2011-07-01

Full Text Available Recent investigations into the neural mechanisms that underlie temporal perception have revealed that the striatum is an important contributor to interval timing processes, and electrophysiological recording studies have shown that the firing rates of striatal neurons are modulated by the time in a trial at which an operant response is made. However, it remains unclear whether striatal firing rate modulations are related to the passage of time alone (i.e., whether temporal information is represented in an abstract manner independent of other attributes of biological importance, or whether this temporal information is embedded within striatal activity related to co-occurring contextual information, such as motor behaviors. This study evaluated these two hypotheses by recording from striatal neurons while rats performed a temporal production task. Rats were trained to respond at different nosepoke apertures for food reward under two simultaneously active reinforcement schedules: a variable-interval (VI-15 sec schedule and a fixed-interval (FI-15 sec schedule of reinforcement. Responding during a trial occurred in a sequential manner composing 3 phases; VI responding, FI responding, VI responding. The vast majority of task-sensitive striatal neurons (95% varied their firing rates associated with equivalent behaviors (e.g., periods in which their snout was held within the nosepoke across these behavioral phases, and 96% of cells varied their firing rates for the same behavior within a phase, thereby demonstrating their sensitivity to time. However, in a direct test of the abstract timing hypothesis, 91% of temporally modulated hold cells were further modulated by the overt motor behaviors associated with transitioning between nosepokes. As such, these data are inconsistent with the striatum representing time in an abstract’ manner, but support the hypothesis that temporal information is embedded within contextual and motor functions of the

Rescaling of temporal expectations during extinction

Science.gov (United States)

Drew, Michael R.; Walsh, Carolyn; Balsam, Peter D

2016-01-01

Previous research suggests that extinction learning is temporally specific. Changing the CS duration between training and extinction can facilitate the loss of the CR within the extinction session but impairs long-term retention of extinction. In two experiments using conditioned magazine approach with rats, we examined the relation between temporal specificity of extinction and CR timing. In Experiment 1 rats were trained on a 12-s, fixed CS-US interval and then extinguished with CS presentations that were 6, 12, or 24 s in duration. The design of Experiment 2 was the same except rats were trained using partial rather than continuous reinforcement. In both experiments, extending the CS duration in extinction facilitated the diminution of CRs during the extinction session, but shortening the CS duration failed to slow extinction. In addition, extending (but not shortening) the CS duration caused temporal rescaling of the CR, in that the peak CR rate migrated later into the trial over the course of extinction training. This migration partially accounted for the faster loss of the CR when the CS duration was extended. Results are incompatible with the hypothesis that extinction is driven by cumulative CS exposure and suggest that temporally extended nonreinforced CS exposure reduces conditioned responding via temporal displacement rather than through extinction per se. PMID:28045291

[Application of Imaging Mass Spectrometry for Drug Discovery].

Science.gov (United States)

Hayasaka, Takahiro

2016-01-01

Imaging mass spectrometry (IMS) can reveal the distribution of biomolecules on tissue sections. In this process, the biomolecules are directly ionized within tissue sections using matrix-assisted laser desorption/ionization, and then their distribution is visualized by pseudo-color based on the relative signal intensity. The biomolecules, such as fatty acids, phospholipids, glycolipids, peptides, proteins, and neurotransmitters, have been analyzed at a spatial resolution of 5 μm. A special instrument for IMS analysis was developed by Shimadzu. The IMS analysis does not require the labeling of biomolecules and is capable of analyzing all the ionized biomolecules. Interest in this method has expanded to many research fields, including biology, agriculture, medicine, and pharmacology. The technique is especially relevant to the drug discovery process. As practiced currently, drug discovery is expensive and time consuming, requiring the preparation of probes for each drug and its metabolites, followed by systematic probe tracking in animal models. The IMS technique is expected to overcome these drawbacks by revealing the distribution of drugs and their metabolites using only a single analysis. In this symposium, I introduced the methodology and applications of IMS and discussed the feasibility of its application to drug discovery in the near future.

The temporal variability of species densities

International Nuclear Information System (INIS)

Redfearn, A.; Pimm, S.L.

1993-01-01

Ecologists use the term 'stability' to mean to number of different things (Pimm 1984a). One use is to equate stability with low variability in population density over time (henceforth, temporal variability). Temporal variability varies greatly from species to species, so what effects it? There are at least three sets of factors: the variability of extrinsic abiotic factors, food web structure, and the intrinsic features of the species themselves. We can measure temporal variability using at least three statistics: the coefficient of variation of density (CV); the standard deviation of the logarithms of density (SDL); and the variance in the differences between logarithms of density for pairs of consecutive years (called annual variability, hence AV, b y Wolda 1978). There are advantages and disadvantages to each measure (Williamson 1984), though in our experience, the measures are strongly correlated across sets of taxonomically related species. The increasing availability of long-term data sets allows one to calculate these statistics for many species and so to begin to understand the various causes of species differences in temporal variability

Temporal contribution to gravitational WKB-like calculations

International Nuclear Information System (INIS)

Akhmedova, Valeria; Pilling, Terry; Gill, Andrea de; Singleton, Douglas

2008-01-01

Recently, it has been shown that the radiation arising from quantum fields placed in a gravitational background (e.g. Hawking radiation) can be derived using a quasi-classical calculation. Here we show that this method has a previously overlooked temporal contribution to the quasi-classical amplitude. The source of this temporal contribution lies in different character of time in general relativity versus quantum mechanics. Only when one takes into account this temporal contribution does one obtain the canonical temperature for the radiation. Although in this Letter the specific example of radiation in de Sitter space-time is used, the temporal contribution is a general contribution to the radiation given off by any gravitational background where the time coordinate changes its signature upon crossing a horizon. Thus, the quasi-classical method for gravitational backgrounds contains subtleties not found in the usual quantum mechanical tunneling problem

Arthritis Genetics Analysis Aids Drug Discovery

Science.gov (United States)

... NIH Research Matters January 13, 2014 Arthritis Genetics Analysis Aids Drug Discovery An international research team identified 42 new ... Edition Distracted Driving Raises Crash Risk Arthritis Genetics Analysis Aids Drug Discovery Oxytocin Affects Facial Recognition Connect with Us ...

Semantics of Temporal Models with Multiple Temporal Dimensions

DEFF Research Database (Denmark)

Kraft, Peter; Sørensen, Jens Otto

ending up with lexical data models. In particular we look upon the representations by sets of normalised tables, by sets of 1NF tables and by sets of N1NF/nested tables. At each translation step we focus on how the temporal semantic is consistently maintained. In this way we recognise the requirements...... for representation of temporal properties in different models and the correspondence between the models. The results rely on the assumptions that the temporal dimensions are interdependent and ordered. Thus for example the valid periods of existences of a property in a mini world are dependent on the transaction...... periods in which the corresponding recordings are valid. This is not the normal way of looking at temporal dimensions and we give arguments supporting our assumption....

MIMIC II: a massive temporal ICU patient database to support research in intelligent patient monitoring

Science.gov (United States)

Saeed, M.; Lieu, C.; Raber, G.; Mark, R. G.

2002-01-01

Development and evaluation of Intensive Care Unit (ICU) decision-support systems would be greatly facilitated by the availability of a large-scale ICU patient database. Following our previous efforts with the MIMIC (Multi-parameter Intelligent Monitoring for Intensive Care) Database, we have leveraged advances in networking and storage technologies to develop a far more massive temporal database, MIMIC II. MIMIC II is an ongoing effort: data is continuously and prospectively archived from all ICU patients in our hospital. MIMIC II now consists of over 800 ICU patient records including over 120 gigabytes of data and is growing. A customized archiving system was used to store continuously up to four waveforms and 30 different parameters from ICU patient monitors. An integrated user-friendly relational database was developed for browsing of patients' clinical information (lab results, fluid balance, medications, nurses' progress notes). Based upon its unprecedented size and scope, MIMIC II will prove to be an important resource for intelligent patient monitoring research, and will support efforts in medical data mining and knowledge-discovery.

Solution NMR Spectroscopy in Target-Based Drug Discovery.

Science.gov (United States)

Li, Yan; Kang, Congbao

2017-08-23

Solution NMR spectroscopy is a powerful tool to study protein structures and dynamics under physiological conditions. This technique is particularly useful in target-based drug discovery projects as it provides protein-ligand binding information in solution. Accumulated studies have shown that NMR will play more and more important roles in multiple steps of the drug discovery process. In a fragment-based drug discovery process, ligand-observed and protein-observed NMR spectroscopy can be applied to screen fragments with low binding affinities. The screened fragments can be further optimized into drug-like molecules. In combination with other biophysical techniques, NMR will guide structure-based drug discovery. In this review, we describe the possible roles of NMR spectroscopy in drug discovery. We also illustrate the challenges encountered in the drug discovery process. We include several examples demonstrating the roles of NMR in target-based drug discoveries such as hit identification, ranking ligand binding affinities, and mapping the ligand binding site. We also speculate the possible roles of NMR in target engagement based on recent processes in in-cell NMR spectroscopy.

Contaminant exposure in relation to spatio-temporal variation in diet composition: A case study of the little owl (Athene noctua)

International Nuclear Information System (INIS)

Schipper, Aafke M.; Wijnhoven, Sander; Baveco, Hans; Brink, Nico W. van den

2012-01-01

We assessed dietary exposure of the little owl Athene noctua to trace metal contamination in a Dutch Rhine River floodplain area. Diet composition was calculated per month for three habitat types, based on the population densities of six prey types (earthworms, ground beetles and four small mammal species) combined with the little owl’s functional response to these prey types. Exposure levels showed a strong positive relationship with the dietary fraction of earthworms, but also depended on the dietary fraction of common voles, with higher common vole fractions resulting in decreasing exposure levels. Spatio-temporal changes in the availability of earthworms and common voles in particular resulted in considerable variation in exposure, with peaks in exposure exceeding a tentative toxicity threshold. These findings imply that wildlife exposure assessments based on a predefined, average diet composition may considerably underestimate local or intermittent peaks in exposure. - Highlights: ► We assessed dietary cadmium exposure of the little owl in a Dutch floodplain. ► Exposure levels were related mainly to the availability of earthworms and voles. ► Diet composition and exposure levels showed large spatio-temporal variation. ► Seasonal peaks in exposure exceeded a tentative toxicity threshold. - Dietary contaminant exposure of opportunistic predators may vary considerably due to spatio-temporal variation in diet.

Temporal networks

CERN Document Server

Saramäki, Jari

2013-01-01

The concept of temporal networks is an extension of complex networks as a modeling framework to include information on when interactions between nodes happen. Many studies of the last decade examine how the static network structure affect dynamic systems on the network. In this traditional approach  the temporal aspects are pre-encoded in the dynamic system model. Temporal-network methods, on the other hand, lift the temporal information from the level of system dynamics to the mathematical representation of the contact network itself. This framework becomes particularly useful for cases where there is a lot of structure and heterogeneity both in the timings of interaction events and the network topology. The advantage compared to common static network approaches is the ability to design more accurate models in order to explain and predict large-scale dynamic phenomena (such as, e.g., epidemic outbreaks and other spreading phenomena). On the other hand, temporal network methods are mathematically and concept...

Bioinformatics for cancer immunotherapy target discovery

DEFF Research Database (Denmark)

Olsen, Lars Rønn; Campos, Benito; Barnkob, Mike Stein

2014-01-01

therapy target discovery in a bioinformatics analysis pipeline. We describe specialized bioinformatics tools and databases for three main bottlenecks in immunotherapy target discovery: the cataloging of potentially antigenic proteins, the identification of potential HLA binders, and the selection epitopes...

On temporality in discourse annotation : Theoretical and practical considerations

NARCIS (Netherlands)

Evers-Vermeul, J.; Hoek, J.; Scholman, M.C.J.

2017-01-01

Temporal information is one of the prominent features that determine the coherence in a discourse. That is why we need an adequate way to deal with this type of information during discourse annotation. In this paper, we will argue that temporal order is a relational rather than a segment-specific

Proteomic and metabolomic approaches to biomarker discovery

CERN Document Server

Issaq, Haleem J

2013-01-01

Proteomic and Metabolomic Approaches to Biomarker Discovery demonstrates how to leverage biomarkers to improve accuracy and reduce errors in research. Disease biomarker discovery is one of the most vibrant and important areas of research today, as the identification of reliable biomarkers has an enormous impact on disease diagnosis, selection of treatment regimens, and therapeutic monitoring. Various techniques are used in the biomarker discovery process, including techniques used in proteomics, the study of the proteins that make up an organism, and metabolomics, the study of chemical fingerprints created from cellular processes. Proteomic and Metabolomic Approaches to Biomarker Discovery is the only publication that covers techniques from both proteomics and metabolomics and includes all steps involved in biomarker discovery, from study design to study execution.  The book describes methods, and presents a standard operating procedure for sample selection, preparation, and storage, as well as data analysis...

Discovery of the Higgs boson

CERN Document Server

Sharma, Vivek

2016-01-01

The recent observation of the Higgs boson has been hailed as the scientific discovery of the century and led to the 2013 Nobel Prize in physics. This book describes the detailed science behind the decades-long search for this elusive particle at the Large Electron Positron Collider at CERN and at the Tevatron at Fermilab and its subsequent discovery and characterization at the Large Hadron Collider at CERN. Written by physicists who played leading roles in this epic search and discovery, this book is an authoritative and pedagogical exposition of the portrait of the Higgs boson that has emerged from a large number of experimental measurements. As the first of its kind, this book should be of interest to graduate students and researchers in particle physics.

Price discovery in European natural gas markets

International Nuclear Information System (INIS)

Schultz, Emma; Swieringa, John

2013-01-01

We provide the first high-frequency investigation of price discovery within the physical and financial layers of Europe's natural gas markets. Testing not only looks at short-term return dynamics, but also considers each security's contribution to price equilibrium in the longer-term. Results show that UK natural gas futures traded on the Intercontinental Exchange display greater price discovery than physical trading at various hubs throughout Europe. - Highlights: • We use intraday data to gauge price discovery in European natural gas markets. • We explore short and long-term dynamics in physical and financial market layers. • Results show ICE's UK natural gas futures are the main venue for price discovery

Intraday Price Discovery in Fragmented Markets

NARCIS (Netherlands)

S.R. Ozturk (Sait); M. van der Wel (Michel); D.J.C. van Dijk (Dick)

2014-01-01

textabstractFor many assets, trading is fragmented across multiple exchanges. Price discovery measures summarize the informativeness of trading on each venue for discovering the asset’s true underlying value. We explore intraday variation in price discovery using a structural model with

Sensation of agency and perception of temporal order.

Science.gov (United States)

Timm, Jana; Schönwiesner, Marc; SanMiguel, Iria; Schröger, Erich

2014-01-01

After adaptation to a fixed temporal delay between actions and their sensory consequences, stimuli delivered during the delay are perceived to occur prior to actions. Temporal judgments are also influenced by the sensation of agency (experience of causing our own actions and their sensory consequences). Sensory consequences of voluntary actions are perceived to occur earlier in time than those of involuntary actions. However, it is unclear whether temporal order illusions influence the sensation of agency. Thus, we tested how the illusionary reversal of motor actions and sound events affect the sensation of agency. We observed an absence of the sensation of agency in the auditory modality in a condition in which sounds were falsely perceived as preceding motor acts relative to the perceived temporal order in the control condition. This finding suggests a strong association between the sensation of agency and the temporal order perception of actions and their consequences. Copyright © 2013 Elsevier Inc. All rights reserved.

The Interactive Role of Temporal Team Leadership in the Telecom Sector of Pakistan: Utilizing Temporal Diversity for Sustainable Knowledge Sharing

Directory of Open Access Journals (Sweden)

Usama Najam

2018-04-01

Full Text Available Human or social dimensions need to be significantly considered to maintain organizational sustainability. Unfortunately, this aspect has received relatively little attention when compared to other dimensions of sustainability. This study promotes the presence of a leader to manage conflicts, which cause hindrances in achieving sustainability. This is possible by maximizing sustainable knowledge sharing in a team, by effectively utilizing temporal diversity, including time urgency, time perspective, and pacing style diversity under a certain time pressure. This study has examined the effect of temporal diversity on knowledge sharing within teams by taking temporal conflict as a mediator. Moreover, it was also investigated whether the role of team temporal leadership is effective in utilizing the conflicts arising from the temporal diversity. The research design was quantitative in nature. A purposive sampling technique was used to gather data from 100 dyads working in the telecom sector of Pakistan, by distributing questionnaires. The findings suggest that team temporal leadership plays an effective role when a conflict arises rather than after it has arisen because more time and resources will be required to resolve such conflicts arising from temporal diversity. When the temporal diversity is low, the leader can manage the conflicts quite well, but as the diversity increases, the role of the temporal leader become much harder which may cause increased conflicts because of the limited capacity of a leader to manage those conflicts. Furthermore, it was observed that conflicts, if managed properly, may lead to increased knowledge sharing.

Temporal Ventriloquism Reveals Intact Audiovisual Temporal Integration in Amblyopia.

Science.gov (United States)

Richards, Michael D; Goltz, Herbert C; Wong, Agnes M F

2018-02-01

We have shown previously that amblyopia involves impaired detection of asynchrony between auditory and visual events. To distinguish whether this impairment represents a defect in temporal integration or nonintegrative multisensory processing (e.g., cross-modal matching), we used the temporal ventriloquism effect in which visual temporal order judgment (TOJ) is normally enhanced by a lagging auditory click. Participants with amblyopia (n = 9) and normally sighted controls (n = 9) performed a visual TOJ task. Pairs of clicks accompanied the two lights such that the first click preceded the first light, or second click lagged the second light by 100, 200, or 450 ms. Baseline audiovisual synchrony and visual-only conditions also were tested. Within both groups, just noticeable differences for the visual TOJ task were significantly reduced compared with baseline in the 100- and 200-ms click lag conditions. Within the amblyopia group, poorer stereo acuity and poorer visual acuity in the amblyopic eye were significantly associated with greater enhancement in visual TOJ performance in the 200-ms click lag condition. Audiovisual temporal integration is intact in amblyopia, as indicated by perceptual enhancement in the temporal ventriloquism effect. Furthermore, poorer stereo acuity and poorer visual acuity in the amblyopic eye are associated with a widened temporal binding window for the effect. These findings suggest that previously reported abnormalities in audiovisual multisensory processing may result from impaired cross-modal matching rather than a diminished capacity for temporal audiovisual integration.

An advanced, new long-legged bird from the Early Cretaceous of the Jehol Group (northeastern China): insights into the temporal divergence of modern birds.

Science.gov (United States)

Liu, Di; Chiappe, Luis M; Zhang, Yuguang; Bell, Alyssa; Meng, Qingjin; Ji, Qiang; Wang, Xuri

2014-11-14

We describe a new ornithuromorph bird species, Gansus zheni from the Lower Cretaceous lacustrine deposits of the Jiufotang Formation (Jehol Group), Liaoning Province, China. A cladistic analysis resolves Gansus zheni as the sister taxon of the roughly contemporaneous Gansus yumenensis (Xiagou Formation, Gansu Province), and together as the most immediate outgroup to Ornithurae. Gansus zheni is the most advanced bird known today for the Jehol Biota. Its discovery provides the best-documented case of inter-basinal correlations (Jehol and Changma basins of Liaoning and Gansu provinces, respectively) using low-taxonomic clades of fossil birds. The existence of close relatives of Ornithurae in deposits formed at about 120 million years ago helps to mitigate the long-standing controversy between molecular and paleontological evidence for the temporal divergence of modern birds (Neornithes).

Memory for relations in the short term and the long term after medial temporal lobe damage.

Science.gov (United States)

Squire, Larry R

2017-05-01

A central idea about the organization of declarative memory and the function of the hippocampus is that the hippocampus provides for the coding of relationships between items. A question arises whether this idea refers to the process of forming long-term memory or whether, as some studies have suggested, memory for relations might depend on the hippocampus even at short retention intervals and even when the task falls within the province of short-term (working) memory. The latter formulation appears to place the operation of relational memory into conflict with the idea that working memory is independent of medial temporal lobe (MTL) structures. In this report, the concepts of relational memory and working memory are discussed in the light of a simple demonstration experiment. Patients with MTL lesions successfully learned and recalled two word pairs when tested directly after learning but failed altogether when tested after a delay. The results do not contradict the idea that the hippocampus has a fundamental role in relational memory. However, there is a need for further elaboration and specification of the idea in order to explain why patients with MTL lesions can establish relational memory in the short term but not in long-term memory. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Quantum Temporal Imaging

OpenAIRE

Tsang, Mankei; Psaltis, Demetri

2006-01-01

The concept of quantum temporal imaging is proposed to manipulate the temporal correlation of entangled photons. In particular, we show that time correlation and anticorrelation can be converted to each other using quantum temporal imaging.

A comparison framework for temporal image reconstructions in electrical impedance tomography

International Nuclear Information System (INIS)

Gagnon, Hervé; Adler, Andy; Grychtol, Bartłomiej

2015-01-01

Electrical impedance tomography (EIT) provides low-resolution images of internal conductivity distributions, but is able to achieve relatively high temporal resolutions. Most EIT image reconstruction algorithms do not explicitly account for the temporal constraints on the measurements or physiological processes under investigation. Instead, algorithms typically assume both that the conductivity distribution does not change during the acquisition of each EIT data frame, and that frames can be reconstructed independently, without consideration of the correlation between images. A failure to account for these temporal effects will result in aliasing-related artefacts in images. Several methods have been proposed to compensate for these effects, including interpolation of raw data, and reconstruction algorithms using Kalman and temporal filtering. However, no systematic work has been performed to understand the severity of the temporal artefacts nor the extent to which algorithms can account for them. We seek to address this need by developing a temporal comparison framework and figures of merit to assess the ability of reconstruction algorithms to account for temporal effects. Using this approach, we compare combinations of three reconstruction algorithms using three EIT data frame types: perfect, realistic and interpolated. The results show that, without accounting for temporal effects, artefacts are present in images for dynamic conductivity contrasts at frequencies 10–20 times slower than the frame rate. The proposed methods show some improvements in reducing these artefacts. (paper)

A Taxonomy of Self-configuring Service Discovery Systems

NARCIS (Netherlands)

Sundramoorthy, V.; Hartel, Pieter H.; Scholten, Johan

2007-01-01

We analyze the fundamental concepts and issues in service discovery. This analysis places service discovery in the context of distributed systems by describing service discovery as a third generation naming system. We also describe the essential architectures and the functionalities in service

High temporal discounters overvalue immediate rewards rather than undervalue future rewards: an event-related brain potential study.

Science.gov (United States)

Cherniawsky, Avital S; Holroyd, Clay B

2013-03-01

Impulsivity is characterized in part by heightened sensitivity to immediate relative to future rewards. Although previous research has suggested that "high discounters" in intertemporal choice tasks tend to prefer immediate over future rewards because they devalue the latter, it remains possible that they instead overvalue immediate rewards. To investigate this question, we recorded the reward positivity, a component of the event-related brain potential (ERP) associated with reward processing, with participants engaged in a task in which they received both immediate and future rewards and nonrewards. The participants also completed a temporal discounting task without ERP recording. We found that immediate but not future rewards elicited the reward positivity. High discounters also produced larger reward positivities to immediate rewards than did low discounters, indicating that high discounters relatively overvalued immediate rewards. These findings suggest that high discounters may be more motivated than low discounters to work for monetary rewards, irrespective of the time of arrival of the incentives.

Discovery stories in the science classroom

Science.gov (United States)

Arya, Diana Jaleh

School science has been criticized for its lack of emphasis on the tentative, dynamic nature of science as a process of learning more about our world. This criticism is the guiding force for this present body of work, which focuses on the question: what are the educational benefits for middle school students of reading texts that highlight the process of science in the form of a discovery narrative? This dissertation traces my journey through a review of theoretical perspectives of narrative, an analysis of first-hand accounts of scientific discovery, the complex process of developing age-appropriate, cohesive and engaging science texts for middle school students, and a comparison study (N=209) that seeks to determine the unique benefits of the scientific discovery narrative for the interest in and retained understanding of conceptual information presented in middle school science texts. A total of 209 middle school participants in nine different classrooms from two different schools participated in the experimental study. Each subject read two science texts that differed in topic (the qualities of and uses for radioactive elements and the use of telescopic technology to see planets in space) and genre (the discovery narrative and the "conceptually known exposition" comparison text). The differences between the SDN and CKE versions for each topic were equivalent in all possible ways (initial introduction, overall conceptual accuracy, elements of human interest, coherence and readability level), save for the unique components of the discovery narrative (i.e., love for their work, acknowledgement of the known, identification of the unknown and the explorative or experimental process to discovery). Participants generally chose the discovery narrative version as the more interesting of the two texts. Additional findings from the experimental study suggest that science texts in the form of SDNs elicit greater long-term retention of key conceptual information, especially

Applied metabolomics in drug discovery.

Science.gov (United States)

Cuperlovic-Culf, M; Culf, A S

2016-08-01

The metabolic profile is a direct signature of phenotype and biochemical activity following any perturbation. Metabolites are small molecules present in a biological system including natural products as well as drugs and their metabolism by-products depending on the biological system studied. Metabolomics can provide activity information about possible novel drugs and drug scaffolds, indicate interesting targets for drug development and suggest binding partners of compounds. Furthermore, metabolomics can be used for the discovery of novel natural products and in drug development. Metabolomics can enhance the discovery and testing of new drugs and provide insight into the on- and off-target effects of drugs. This review focuses primarily on the application of metabolomics in the discovery of active drugs from natural products and the analysis of chemical libraries and the computational analysis of metabolic networks. Metabolomics methodology, both experimental and analytical is fast developing. At the same time, databases of compounds are ever growing with the inclusion of more molecular and spectral information. An increasing number of systems are being represented by very detailed metabolic network models. Combining these experimental and computational tools with high throughput drug testing and drug discovery techniques can provide new promising compounds and leads.

Discovery of the cancer stem cell related determinants of radioresistance

International Nuclear Information System (INIS)

Peitzsch, Claudia; Kurth, Ina; Kunz-Schughart, Leoni; Baumann, Michael; Dubrovska, Anna

2013-01-01

Tumors are known to be heterogeneous containing a dynamic mixture of phenotypically and functionally different tumor cells. The two concepts attempting to explain the origin of intratumor heterogeneity are the cancer stem cell hypothesis and the clonal evolution model. The stochastic model argues that tumors are biologically homogenous and all cancer cells within the tumor have equal ability to propagate the tumor growth depending on continuing mutations and selective pressure. By contrast, the stem cells model suggests that cancer heterogeneity is due to the hierarchy that originates from a small population of cancer stem cells (CSCs) which are biologically distinct from the bulk tumor and possesses self-renewal, tumorigenic and multilineage potential. Although these two hypotheses have been discussed for a long time as mutually exclusive explanations of tumor heterogeneity, they are easily reconciled serving as a driving force of cancer evolution and diversity. Recent discovery of the cancer cell plasticity and heterogeneity makes the CSC population a moving target that could be hard to track and eradicate. Understanding the signaling mechanisms regulating CSCs during the course of cancer treatment can be indispensable for the optimization of current treatment strategies

Computed tomography of temporal bone fractures and temporal region anatomy in horses.

Science.gov (United States)

Pownder, S; Scrivani, P V; Bezuidenhout, A; Divers, T J; Ducharme, N G

2010-01-01

In people, specific classifications of temporal bone fractures are associated with clinical signs and prognosis. In horses, similar classifications have not been evaluated and might be useful establishing prognosis or understanding pathogenesis of certain types of trauma. We hypothesized associations between temporal bone fracture location and orientation in horses detected during computed tomography (CT) and frequency of facial nerve (CN7) deficit, vestibulocochlear nerve (CN8) deficit, or temporohyoid osteoarthropathy (THO). Complex temporal region anatomy may confound fracture identification, and consequently a description of normal anatomy was included. All horses undergoing temporal region CT at our hospital between July 1998 and May 2008. Data were collected retrospectively, examiners were blinded, and relationships were investigated among temporal bone fractures, ipsilateral THO, ipsilateral CN7, or ipsilateral CN8 deficits by Chi-square or Fischer's exact tests. Seventy-nine horses had CT examinations of the temporal region (158 temporal bones). Sixteen temporal bone fractures were detected in 14 horses. Cranial nerve deficits were seen with fractures in all parts of the temporal bone (petrosal, squamous, and temporal) and, temporal bone fractures were associated with CN7 and CN8 deficits and THO. No investigated fracture classification scheme, however, was associated with specific cranial nerve deficits. Without knowledge of the regional anatomy, normal structures may be mistaken for a temporal bone fracture or vice versa. Although no fracture classification scheme was associated with the assessed clinical signs, simple descriptive terminology (location and orientation) is recommended for reporting and facilitating future comparisons.

Young women do it better: sexual dimorphism in temporal discrimination.

Directory of Open Access Journals (Sweden)

Laura Jane Williams

2015-07-01

Full Text Available The temporal discrimination threshold is the shortest time interval at which two sensory stimuli presented sequentially are detected as asynchronous by the observer. Temporal discrimination thresholds are known to increase with age. Having previously observed shorter thresholds in young women than in men, in this work we sought to sytematically examine the effect of sex and age on temporal discrimination. The aims of this study were to examine, in a large group of men and women aged 20 to 65 years, the distribution of temporal discrimination thresholds with an analysis of the individual participant’s responses, assessing the point of subjective equality (PSE and the just noticeable difference (JND. These respectively assess sensitivity and accuracy of an individual’s response. In 175 participants (88 women aged 20-65 years, temporal discrimination was faster in women than in men under the age of 40 years by a mean of approximately 13ms. However age-related decline in temporal discrimination was three times faster in women so that, in the age group of 40-65 years, the female superiority was reversed. The point of subjective equality showed a similar advantage in younger women and more marked age-related decline in women than men, as the temporal discrimination threshold. Just noticeable difference values declined equally in both sexes showing no sexual dimorphism. This observed sexual dimorphism in temporal discrimination is important for both a future clinical research assessing disordered mid-brain covert attention in basal-ganglia disorders and b understanding the biology of this sexual dimorphism which may be genetic or hormonal.

Use of allosteric targets in the discovery of safer drugs.

Science.gov (United States)

Grover, Ashok Kumar

2013-01-01

The need for drugs with fewer side effects cannot be overemphasized. Today, most drugs modify the actions of enzymes, receptors, transporters and other molecules by directly binding to their active (orthosteric) sites. However, orthosteric site configuration is similar in several proteins performing related functions and this leads to a lower specificity of a drug for the desired protein. Consequently, such drugs may have adverse side effects. A new basis of drug discovery is emerging based on the binding of the drug molecules to sites away (allosteric) from the orthosteric sites. It is possible to find allosteric sites which are unique and hence more specific as targets for drug discovery. Of many available examples, two are highlighted here. The first is caloxins - a new class of highly specific inhibitors of plasma membrane Ca²⁺ pumps. The second concerns the modulation of receptors for the neurotransmitter acetylcholine, which binds to 12 types of receptors. Exploitation of allosteric sites has led to the discovery of drugs which can selectively modulate the activation of only 1 (M1 muscarinic) out of the 12 different types of acetylcholine receptors. These drugs are being tested for schizophrenia treatment. It is anticipated that the drug discovery exploiting allosteric sites will lead to more effective therapeutic agents with fewer side effects. Copyright © 2013 S. Karger AG, Basel.

Fragment-based approaches to the discovery of kinase inhibitors.

Science.gov (United States)

Mortenson, Paul N; Berdini, Valerio; O'Reilly, Marc

2014-01-01

Protein kinases are one of the most important families of drug targets, and aberrant kinase activity has been linked to a large number of disease areas. Although eminently targetable using small molecules, kinases present a number of challenges as drug targets, not least obtaining selectivity across such a large and relatively closely related target family. Fragment-based drug discovery involves screening simple, low-molecular weight compounds to generate initial hits against a target. These hits are then optimized to more potent compounds via medicinal chemistry, usually facilitated by structural biology. Here, we will present a number of recent examples of fragment-based approaches to the discovery of kinase inhibitors, detailing the construction of fragment-screening libraries, the identification and validation of fragment hits, and their optimization into potent and selective lead compounds. The advantages of fragment-based methodologies will be discussed, along with some of the challenges associated with using this route. Finally, we will present a number of key lessons derived both from our own experience running fragment screens against kinases and from a large number of published studies.

Temporal Lobe Reactions After Carbon Ion Radiation Therapy: Comparison of Relative Biological Effectiveness–Weighted Tolerance Doses Predicted by Local Effect Models I and IV

Energy Technology Data Exchange (ETDEWEB)

Gillmann, Clarissa, E-mail: clarissa.gillmann@med.uni-heidelberg.de [Department of Radiation Oncology and Radiation Therapy, Heidelberg University Hospital, Heidelberg (Germany); Jäkel, Oliver [Department of Radiation Oncology and Radiation Therapy, Heidelberg University Hospital, Heidelberg (Germany); Heidelberg Ion Beam Therapy Center (HIT), Heidelberg (Germany); Department of Medical Physics in Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg (Germany); Schlampp, Ingmar [Department of Radiation Oncology and Radiation Therapy, Heidelberg University Hospital, Heidelberg (Germany); Karger, Christian P. [Department of Medical Physics in Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg (Germany)

2014-04-01

Purpose: To compare the relative biological effectiveness (RBE)–weighted tolerance doses for temporal lobe reactions after carbon ion radiation therapy using 2 different versions of the local effect model (LEM I vs LEM IV) for the same patient collective under identical conditions. Methods and Materials: In a previous study, 59 patients were investigated, of whom 10 experienced temporal lobe reactions (TLR) after carbon ion radiation therapy for low-grade skull-base chordoma and chondrosarcoma at Helmholtzzentrum für Schwerionenforschung (GSI) in Darmstadt, Germany in 2002 and 2003. TLR were detected as visible contrast enhancements on T1-weighted MRI images within a median follow-up time of 2.5 years. Although the derived RBE-weighted temporal lobe doses were based on the clinically applied LEM I, we have now recalculated the RBE-weighted dose distributions using LEM IV and derived dose-response curves with Dmax,V-1 cm³ (the RBE-weighted maximum dose in the remaining temporal lobe volume, excluding the volume of 1 cm³ with the highest dose) as an independent dosimetric variable. The resulting RBE-weighted tolerance doses were compared with those of the previous study to assess the clinical impact of LEM IV relative to LEM I. Results: The dose-response curve of LEM IV is shifted toward higher values compared to that of LEM I. The RBE-weighted tolerance dose for a 5% complication probability (TD{sub 5}) increases from 68.8 ± 3.3 to 78.3 ± 4.3 Gy (RBE) for LEM IV as compared to LEM I. Conclusions: LEM IV predicts a clinically significant increase of the RBE-weighted tolerance doses for the temporal lobe as compared to the currently applied LEM I. The limited available photon data do not allow a final conclusion as to whether RBE predictions of LEM I or LEM IV better fit better clinical experience in photon therapy. The decision about a future clinical application of LEM IV therefore requires additional analysis of temporal lobe reactions in a

Predicting future discoveries from current scientific literature.

Science.gov (United States)

Petrič, Ingrid; Cestnik, Bojan

2014-01-01

Knowledge discovery in biomedicine is a time-consuming process starting from the basic research, through preclinical testing, towards possible clinical applications. Crossing of conceptual boundaries is often needed for groundbreaking biomedical research that generates highly inventive discoveries. We demonstrate the ability of a creative literature mining method to advance valuable new discoveries based on rare ideas from existing literature. When emerging ideas from scientific literature are put together as fragments of knowledge in a systematic way, they may lead to original, sometimes surprising, research findings. If enough scientific evidence is already published for the association of such findings, they can be considered as scientific hypotheses. In this chapter, we describe a method for the computer-aided generation of such hypotheses based on the existing scientific literature. Our literature-based discovery of NF-kappaB with its possible connections to autism was recently approved by scientific community, which confirms the ability of our literature mining methodology to accelerate future discoveries based on rare ideas from existing literature.

On the Spatial and Temporal Sampling Errors of Remotely Sensed Precipitation Products

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Ali Behrangi

2017-11-01

Full Text Available Observation with coarse spatial and temporal sampling can cause large errors in quantification of the amount, intensity, and duration of precipitation events. In this study, the errors resulting from temporal and spatial sampling of precipitation events were quantified and examined using the latest version (V4 of the Global Precipitation Measurement (GPM mission integrated multi-satellite retrievals for GPM (IMERG, which is available since spring of 2014. Relative mean square error was calculated at 0.1° × 0.1° every 0.5 h between the degraded (temporally and spatially and original IMERG products. The temporal and spatial degradation was performed by producing three-hour (T3, six-hour (T6, 0.5° × 0.5° (S5, and 1.0° × 1.0° (S10 maps. The results show generally larger errors over land than ocean, especially over mountainous regions. The relative error of T6 is almost 20% larger than T3 over tropical land, but is smaller in higher latitudes. Over land relative error of T6 is larger than S5 across all latitudes, while T6 has larger relative error than S10 poleward of 20°S–20°N. Similarly, the relative error of T3 exceeds S5 poleward of 20°S–20°N, but does not exceed S10, except in very high latitudes. Similar results are also seen over ocean, but the error ratios are generally less sensitive to seasonal changes. The results also show that the spatial and temporal relative errors are not highly correlated. Overall, lower correlations between the spatial and temporal relative errors are observed over ocean than over land. Quantification of such spatiotemporal effects provides additional insights into evaluation studies, especially when different products are cross-compared at a range of spatiotemporal scales.

Verification of a Method for Measuring Parkinson’s Disease Related Temporal Irregularity in Spiral Drawings

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Somayeh Aghanavesi

2017-10-01

Full Text Available Parkinson’s disease (PD is a progressive movement disorder caused by the death of dopamine-producing cells in the midbrain. There is a need for frequent symptom assessment, since the treatment needs to be individualized as the disease progresses. The aim of this paper was to verify and further investigate the clinimetric properties of an entropy-based method for measuring PD-related upper limb temporal irregularities during spiral drawing tasks. More specifically, properties of a temporal irregularity score (TIS for patients at different stages of PD, and medication time points were investigated. Nineteen PD patients and 22 healthy controls performed repeated spiral drawing tasks on a smartphone. Patients performed the tests before a single levodopa dose and at specific time intervals after the dose was given. Three movement disorder specialists rated videos of the patients based on the unified PD rating scale (UPDRS and the Dyskinesia scale. Differences in mean TIS between the groups of patients and healthy subjects were assessed. Test-retest reliability of the TIS was measured. The ability of TIS to detect changes from baseline (before medication to later time points was investigated. Correlations between TIS and clinical rating scores were assessed. The mean TIS was significantly different between healthy subjects and patients in advanced groups (p-value = 0.02. Test-retest reliability of TIS was good with Intra-class Correlation Coefficient of 0.81. When assessing changes in relation to treatment, TIS contained some information to capture changes from Off to On and wearing off effects. However, the correlations between TIS and clinical scores (UPDRS and Dyskinesia were weak. TIS was able to differentiate spiral drawings drawn by patients in an advanced stage from those drawn by healthy subjects, and TIS had good test-retest reliability. TIS was somewhat responsive to single-dose levodopa treatment. Since TIS is an upper limb high

The neutron discovery

International Nuclear Information System (INIS)

Six, J.

1987-01-01

The neutron: who had first the idea, who discovered it, who established its main properties. To these apparently simple questions, multiple answers exist. The progressive discovery of the neutron is a marvellous illustration of some characteristics of the scientific research, where the unforeseen may be combined with the expected. This discovery is replaced in the context of the 1930's scientific effervescence that succeeded the revolutionary introduction of quantum mechanics. This book describes the works of Bothe, the Joliot-Curie and Chadwick which led to the neutron in an unexpected way. A historical analysis allows to give a new interpretation on the hypothesis suggested by the Joliot-Curie. Some texts of these days will help the reader to revive this fascinating story [fr

Viral pathogen discovery

Science.gov (United States)

Chiu, Charles Y

2015-01-01

Viral pathogen discovery is of critical importance to clinical microbiology, infectious diseases, and public health. Genomic approaches for pathogen discovery, including consensus polymerase chain reaction (PCR), microarrays, and unbiased next-generation sequencing (NGS), have the capacity to comprehensively identify novel microbes present in clinical samples. Although numerous challenges remain to be addressed, including the bioinformatics analysis and interpretation of large datasets, these technologies have been successful in rapidly identifying emerging outbreak threats, screening vaccines and other biological products for microbial contamination, and discovering novel viruses associated with both acute and chronic illnesses. Downstream studies such as genome assembly, epidemiologic screening, and a culture system or animal model of infection are necessary to establish an association of a candidate pathogen with disease. PMID:23725672

Relation of callosal structure to cognitive abilities in temporal lobe epilepsy

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Christine eSchneider

2014-02-01

Full Text Available The main objective of this paper is to analyse the influence of mesial temporal lobe epilepsy (TLE on the morphology of the corpus callosum (CC and its relation to cognitive abilities. More specifically, we investigated correlations between intellectual abilities and callosal morphology, while additionally exploring the modulating impact of (a side of seizure onset (b age of disease onset.For this reason a large representative sample of patients with hippocampal sclerosis (n=79; 35 males; 44 females; age: 18-63 years with disease onset ranging from 0 to 50 years of age, and consisting of 46 left and 33 right TLE patients was recruited. Intelligence was measured using the Wechsler Adult Intelligence Scale Revised (WAIS-R.To get localizations of correlations with high anatomic precision, callosal morphology was examined using computational mesh-based modeling methods, applied to anatomical brain MRI scans.Intellectual performance was positively associated with callosal thickness in anterior and midcallosal callosal regions, with anterior parts being slightly more affected by age of disease onset and side of seizure onset than posterior parts. Earlier age at onset of epilepsy was associated with lower thickness in anterior and midcallosal regions. In addition, laterality of seizure onset had a significant influence on anterior CC morphology, with left hemispheric origin having stronger effects.We found that in TLE, anterior and midcallosal CC morphology are related to cognitive performance. The findings support recent findings of detrimental effects of early onset mTLE on anterior brain regions and of a distinct effect particularly of left TLE on frontal lobe functioning and structure. The causal nature of the relationship remains an open question, i.e., whether CC morphology impacts IQ development or whether IQ development impacts CC morphology, or both.

Competitive Semantic Memory Retrieval: Temporal Dynamics Revealed by Event-Related Potentials.

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Robin Hellerstedt

Full Text Available Memories compete for retrieval when they are related to a common retrieval cue. Previous research has shown that retrieval of a target memory may lead to subsequent retrieval-induced forgetting (RIF of currently irrelevant competing memories. In the present study, we investigated the time course of competitive semantic retrieval and examined the neurocognitive mechanisms underlying RIF. We contrasted two theoretical accounts of RIF by examining a critical aspect of this memory phenomenon, namely the extent to which it depends on successful retrieval of the target memory. Participants first studied category-exemplar word-pairs (e.g. Fruit-Apple. Next, we recorded electrophysiological measures of brain activity while the participants performed a competitive semantic cued-recall task. In this task, the participants were provided with the studied categories but they were instructed to retrieve other unstudied exemplars (e.g. Fruit-Ma__?. We investigated the event-related potential (ERP correlates of retrieval success by comparing ERPs from successful and failed retrieval trials. To isolate the ERP correlates of continuous retrieval attempts from the ERP correlates of retrieval success, we included an impossible retrieval condition, with incompletable word-stem cues (Drinks-Wy__ and compared it with a non-retrieval presentation baseline condition (Occupation-Dentist. The participants' memory for all the studied exemplars was tested in the final phase of the experiment. Taken together, the behavioural results suggest that RIF is independent of target retrieval. Beyond investigating the mechanisms underlying RIF, the present study also elucidates the temporal dynamics of semantic cued-recall by isolating the ERP correlates of retrieval attempt and retrieval success. The ERP results revealed that retrieval attempt is reflected in a late posterior negativity, possibly indicating construction of candidates for completing the word-stem cue and retrieval

Competitive Semantic Memory Retrieval: Temporal Dynamics Revealed by Event-Related Potentials

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Hellerstedt, Robin; Johansson, Mikael

2016-01-01

Memories compete for retrieval when they are related to a common retrieval cue. Previous research has shown that retrieval of a target memory may lead to subsequent retrieval-induced forgetting (RIF) of currently irrelevant competing memories. In the present study, we investigated the time course of competitive semantic retrieval and examined the neurocognitive mechanisms underlying RIF. We contrasted two theoretical accounts of RIF by examining a critical aspect of this memory phenomenon, namely the extent to which it depends on successful retrieval of the target memory. Participants first studied category-exemplar word-pairs (e.g. Fruit—Apple). Next, we recorded electrophysiological measures of brain activity while the participants performed a competitive semantic cued-recall task. In this task, the participants were provided with the studied categories but they were instructed to retrieve other unstudied exemplars (e.g. Fruit—Ma__?). We investigated the event-related potential (ERP) correlates of retrieval success by comparing ERPs from successful and failed retrieval trials. To isolate the ERP correlates of continuous retrieval attempts from the ERP correlates of retrieval success, we included an impossible retrieval condition, with incompletable word-stem cues (Drinks—Wy__) and compared it with a non-retrieval presentation baseline condition (Occupation—Dentist). The participants’ memory for all the studied exemplars was tested in the final phase of the experiment. Taken together, the behavioural results suggest that RIF is independent of target retrieval. Beyond investigating the mechanisms underlying RIF, the present study also elucidates the temporal dynamics of semantic cued-recall by isolating the ERP correlates of retrieval attempt and retrieval success. The ERP results revealed that retrieval attempt is reflected in a late posterior negativity, possibly indicating construction of candidates for completing the word-stem cue and retrieval

Competitive Semantic Memory Retrieval: Temporal Dynamics Revealed by Event-Related Potentials.

Science.gov (United States)

Hellerstedt, Robin; Johansson, Mikael

2016-01-01

Memories compete for retrieval when they are related to a common retrieval cue. Previous research has shown that retrieval of a target memory may lead to subsequent retrieval-induced forgetting (RIF) of currently irrelevant competing memories. In the present study, we investigated the time course of competitive semantic retrieval and examined the neurocognitive mechanisms underlying RIF. We contrasted two theoretical accounts of RIF by examining a critical aspect of this memory phenomenon, namely the extent to which it depends on successful retrieval of the target memory. Participants first studied category-exemplar word-pairs (e.g. Fruit-Apple). Next, we recorded electrophysiological measures of brain activity while the participants performed a competitive semantic cued-recall task. In this task, the participants were provided with the studied categories but they were instructed to retrieve other unstudied exemplars (e.g. Fruit-Ma__?). We investigated the event-related potential (ERP) correlates of retrieval success by comparing ERPs from successful and failed retrieval trials. To isolate the ERP correlates of continuous retrieval attempts from the ERP correlates of retrieval success, we included an impossible retrieval condition, with incompletable word-stem cues (Drinks-Wy__) and compared it with a non-retrieval presentation baseline condition (Occupation-Dentist). The participants' memory for all the studied exemplars was tested in the final phase of the experiment. Taken together, the behavioural results suggest that RIF is independent of target retrieval. Beyond investigating the mechanisms underlying RIF, the present study also elucidates the temporal dynamics of semantic cued-recall by isolating the ERP correlates of retrieval attempt and retrieval success. The ERP results revealed that retrieval attempt is reflected in a late posterior negativity, possibly indicating construction of candidates for completing the word-stem cue and retrieval monitoring

Living in the Past, Present, and Future: Measuring Temporal Orientation With Language.

Science.gov (United States)

Park, Gregory; Schwartz, H Andrew; Sap, Maarten; Kern, Margaret L; Weingarten, Evan; Eichstaedt, Johannes C; Berger, Jonah; Stillwell, David J; Kosinski, Michal; Ungar, Lyle H; Seligman, Martin E P

2017-04-01

Temporal orientation refers to individual differences in the relative emphasis one places on the past, present, or future, and it is related to academic, financial, and health outcomes. We propose and evaluate a method for automatically measuring temporal orientation through language expressed on social media. Judges rated the temporal orientation of 4,302 social media messages. We trained a classifier based on these ratings, which could accurately predict the temporal orientation of new messages in a separate validation set (accuracy/mean sensitivity = .72; mean specificity = .77). We used the classifier to automatically classify 1.3 million messages written by 5,372 participants (50% female; ages 13-48). Finally, we tested whether individual differences in past, present, and future orientation differentially related to gender, age, Big Five personality, satisfaction with life, and depressive symptoms. Temporal orientations exhibit several expected correlations with age, gender, and Big Five personality. More future-oriented people were older, more likely to be female, more conscientious, less impulsive, less depressed, and more satisfied with life; present orientation showed the opposite pattern. Language-based assessments can complement and extend existing measures of temporal orientation, providing an alternative approach and additional insights into language and personality relationships. © 2015 Wiley Periodicals, Inc.

Intestinal microbiota in healthy adults: temporal analysis reveals individual and common core and relation to intestinal symptoms.

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Jonna Jalanka-Tuovinen

Full Text Available While our knowledge of the intestinal microbiota during disease is accumulating, basic information of the microbiota in healthy subjects is still scarce. The aim of this study was to characterize the intestinal microbiota of healthy adults and specifically address its temporal stability, core microbiota and relation with intestinal symptoms. We carried out a longitudinal study by following a set of 15 healthy Finnish subjects for seven weeks and regularly assessed their intestinal bacteria and archaea with the Human Intestinal Tract (HIT Chip, a phylogenetic microarray, in conjunction with qPCR analyses. The health perception and occurrence of intestinal symptoms was recorded by questionnaire at each sampling point.A high overall temporal stability of the microbiota was observed. Five subjects showed transient microbiota destabilization, which correlated not only with the intake of antibiotics but also with overseas travelling and temporary illness, expanding the hitherto known factors affecting the intestinal microbiota. We identified significant correlations between the microbiota and common intestinal symptoms, including abdominal pain and bloating. The most striking finding was the inverse correlation between Bifidobacteria and abdominal pain: subjects who experienced pain had over five-fold less Bifidobacteria compared to those without pain. Finally, a novel computational approach was used to define the common core microbiota, highlighting the role of the analysis depth in finding the phylogenetic core and estimating its size. The in-depth analysis suggested that we share a substantial number of our intestinal phylotypes but as they represent highly variable proportions of the total community, many of them often remain undetected.A global and high-resolution microbiota analysis was carried out to determine the temporal stability, the associations with intestinal symptoms, and the individual and common core microbiota in healthy adults. The

An invertebrate model for CNS drug discovery

DEFF Research Database (Denmark)

Al-Qadi, Sonia; Schiøtt, Morten; Hansen, Steen Honoré

2015-01-01

BACKGROUND: ABC efflux transporters at the blood brain barrier (BBB), namely the P-glycoprotein (P-gp), restrain the development of central nervous system (CNS) drugs. Consequently, early screening of CNS drug candidates is pivotal to identify those affected by efflux activity. Therefore, simple,...... barriers. CONCLUSION: Findings suggest a conserved mechanism of brain efflux activity between insects and vertebrates, confirming that this model holds promise for inexpensive and high-throughput screening relative to in vivo models, for CNS drug discovery....

A Probabilistic Framework for Constructing Temporal Relations in Replica Exchange Molecular Trajectories.

Science.gov (United States)

Chattopadhyay, Aditya; Zheng, Min; Waller, Mark Paul; Priyakumar, U Deva

2018-05-23

Knowledge of the structure and dynamics of biomolecules is essential for elucidating the underlying mechanisms of biological processes. Given the stochastic nature of many biological processes, like protein unfolding, it's almost impossible that two independent simulations will generate the exact same sequence of events, which makes direct analysis of simulations difficult. Statistical models like Markov Chains, transition networks etc. help in shedding some light on the mechanistic nature of such processes by predicting long-time dynamics of these systems from short simulations. However, such methods fall short in analyzing trajectories with partial or no temporal information, for example, replica exchange molecular dynamics or Monte Carlo simulations. In this work we propose a probabilistic algorithm, borrowing concepts from graph theory and machine learning, to extract reactive pathways from molecular trajectories in the absence of temporal data. A suitable vector representation was chosen to represent each frame in the macromolecular trajectory (as a series of interaction and conformational energies) and dimensionality reduction was performed using principal component analysis (PCA). The trajectory was then clustered using a density-based clustering algorithm, where each cluster represents a metastable state on the potential energy surface (PES) of the biomolecule under study. A graph was created with these clusters as nodes with the edges learnt using an iterative expectation maximization algorithm. The most reactive path is conceived as the widest path along this graph. We have tested our method on RNA hairpin unfolding trajectory in aqueous urea solution. Our method makes the understanding of the mechanism of unfolding in RNA hairpin molecule more tractable. As this method doesn't rely on temporal data it can be used to analyze trajectories from Monte Carlo sampling techniques and replica exchange molecular dynamics (REMD).

Entropy uncertainty relations and stability of phase-temporal quantum cryptography with finite-length transmitted strings

Energy Technology Data Exchange (ETDEWEB)

Molotkov, S. N., E-mail: sergei.molotkov@gmail.com [Russian Federation, Academy of Cryptography (Russian Federation)

2012-12-15

Any key-generation session contains a finite number of quantum-state messages, and it is there-fore important to understand the fundamental restrictions imposed on the minimal length of a string required to obtain a secret key with a specified length. The entropy uncertainty relations for smooth min and max entropies considerably simplify and shorten the proof of security. A proof of security of quantum key distribution with phase-temporal encryption is presented. This protocol provides the maximum critical error compared to other protocols up to which secure key distribution is guaranteed. In addition, unlike other basic protocols (of the BB84 type), which are vulnerable with respect to an attack by 'blinding' of avalanche photodetectors, this protocol is stable with respect to such an attack and guarantees key security.

Entropy uncertainty relations and stability of phase-temporal quantum cryptography with finite-length transmitted strings

International Nuclear Information System (INIS)

Molotkov, S. N.

2012-01-01

Any key-generation session contains a finite number of quantum-state messages, and it is there-fore important to understand the fundamental restrictions imposed on the minimal length of a string required to obtain a secret key with a specified length. The entropy uncertainty relations for smooth min and max entropies considerably simplify and shorten the proof of security. A proof of security of quantum key distribution with phase-temporal encryption is presented. This protocol provides the maximum critical error compared to other protocols up to which secure key distribution is guaranteed. In addition, unlike other basic protocols (of the BB84 type), which are vulnerable with respect to an attack by “blinding” of avalanche photodetectors, this protocol is stable with respect to such an attack and guarantees key security.

Integrating what and when across the primate medial temporal lobe.

Science.gov (United States)

Naya, Yuji; Suzuki, Wendy A

2011-08-05

Episodic memory or memory for the detailed events in our lives is critically dependent on structures of the medial temporal lobe (MTL). A fundamental component of episodic memory is memory for the temporal order of items within an episode. To understand the contribution of individual MTL structures to temporal-order memory, we recorded single-unit activity and local field potential from three MTL areas (hippocampus and entorhinal and perirhinal cortex) and visual area TE as monkeys performed a temporal-order memory task. Hippocampus provided incremental timing signals from one item presentation to the next, whereas perirhinal cortex signaled the conjunction of items and their relative temporal order. Thus, perirhinal cortex appeared to integrate timing information from hippocampus with item information from visual sensory area TE.

The Structural Plasticity of White Matter Networks Following Anterior Temporal Lobe Resection

Science.gov (United States)

Yogarajah, Mahinda; Focke, Niels K.; Bonelli, Silvia B.; Thompson, Pamela; Vollmar, Christian; McEvoy, Andrew W.; Alexander, Daniel C.; Symms, Mark R.; Koepp, Matthias J.; Duncan, John S.

2010-01-01

Anterior temporal lobe resection is an effective treatment for refractory temporal lobe epilepsy. The structural consequences of such surgery in the white matter, and how these relate to language function after surgery remain unknown. We carried out a longitudinal study with diffusion tensor imaging in 26 left and 20 right temporal lobe epilepsy…

The role of medial temporal lobe in retrieving spatial and nonspatial relations from episodic and semantic memory.

Science.gov (United States)

Ryan, Lee; Lin, Chun-Yu; Ketcham, Katie; Nadel, Lynn

2010-01-01

This study examined the involvement of medial temporal lobe, especially the hippocampus, in processing spatial and nonspatial relations using episodic and semantic versions of a relational judgment task. Participants studied object arrays and were tested on different types of relations between pairs of objects. Three prevalent views of hippocampal function were considered. Cognitive map theory (O'Keefe and Nadel (1978) The Hippocampus as a Cognitive Map. USA: Oxford University Press) emphasizes hippocampal involvement in spatial relational tasks. Multiple trace theory (Nadel and Moscovitch (1997) Memory consolidation, retrograde amnesia and the hippocampal complex Curr Opin Neurobiol 7:217-227) emphasizes hippocampal involvement in episodic tasks. Eichenbaum and Cohen's ((2001) From Conditioning to Conscious Recollection: Memory Systems of the Brain. USA: Oxford University Press) relational theory predicts equivalent hippocampal involvement in all relational tasks within both semantic and episodic memory. The fMRI results provided partial support for all three theories, though none of them fit the data perfectly. We observed hippocampal activation during all relational tasks, with increased activation for spatial compared to nonspatial relations, and for episodic compared to semantic relations. The placement of activation along the anterior-posterior axis of the hippocampus also differentiated the conditions. We suggest a view of hippocampal function in memory that incorporates aspects of all three theories. Copyright 2009 Wiley-Liss, Inc.

Synesthetic associations and psychosensory symptoms of temporal epilepsy

Directory of Open Access Journals (Sweden)

Neckar M

2016-01-01

Full Text Available Marcel Neckar, Petr Bob Center for Neuropsychiatric Research of Traumatic Stress, Department of Psychiatry, First Faculty of Medicine, Charles University, Prague, Czech Republic Background: Synesthesia manifests as unusual associative connections that may cause intriguing experiences due to various cross-modal connections, for example, a sound may be experienced as color. Several findings indicate that temporal lobe seizures or seizure-like conditions and increased excitability may influence various unusual cross-sensory links and synesthetic experiences.Methods: In this context, the purpose of this study is to find relationships between word–color associations and psychopathological symptoms related to temporal lobe epilepsy and limbic irritability (Limbic System Checklist [LSCL-33], symptoms of traumatic stress (Trauma Symptoms Checklist [TSC-40], and depressive symptoms (Beck Depression Inventory [BDI-II] in 71 participants (mean age =25.23 years recruited from the general population. The whole sample included two subgroups according to levels of psychosensory and affective symptoms related to temporal epilepsy measured by LSCL-33.Results: The results in both subgroups indicate specific words correlated with the scores of psychopathological symptoms measured by LSCL-33, BDI-II, and TSC-40. Significant Spearman correlations have been predominantly found in the subgroup of participants with higher levels of LSCL-33.Conclusion: The results indicate a specific synesthetic-like mechanism in association processes that reflects psychopathological symptoms related to increased temporo-limbic excitability. Keywords: word associations, colors, stress, synesthesia, temporal lobe epilepsy, limbic irritability

Temporal relation between temperature change and FDG uptake in brown adipose tissue

International Nuclear Information System (INIS)

Kim, SunHee; Krynyckyi, Borys R.; Machac, Josef; Kim, Chun K.

2008-01-01

It has been reported that the prevalence of 18 F fluorodeoxyglucose (FDG) uptake in brown adipose tissue (BAT) is related to outdoor temperature, i.e., more frequent during the colder periods of the year. The purpose of this study was to assess the temporal relationship between BAT FDG uptake and temperature. We correlated the prevalence of BAT with average temperatures (divided into five temperature ranges) of seven different durations. One thousand four hundred ninety-five consecutive FDG Positron emission tomography (PET) studies in 1,159 patients (566 male and 593 female, mean age = 60.4 years) were retrospectively reviewed. FDG uptake with distinct patterns compatible with BAT was identified by a consensus of two readers. The local daily average temperature from January 2000 to November 2003 (beginning 60 days before the date of first PET scan) were obtained, and 2-, 3-, 7-, 14-, 30-, and 60-day average temperatures before the date of a PET study were calculated. The prevalence of BAT FDG uptake was correlated with these various average temperatures. The daily, 2-day, 3-day, and 7-day average temperature had an inverse relation with the prevalence of BAT, i.e., the lower the temperature, the higher prevalence of BAT. When the temperature was averaged over 14 days or longer, this inverse relationship between the temperature and the prevalence of BAT was no longer preserved. Our data suggest that increased FDG uptake in BAT occurs more often as an acute response to cold weather (1-7 days) rather than to prolonged periods of average cold weather. (orig.)

Discovery of Cationic Polymers for Non-viral Gene Delivery using Combinatorial Approaches

Science.gov (United States)

Barua, Sutapa; Ramos, James; Potta, Thrimoorthy; Taylor, David; Huang, Huang-Chiao; Montanez, Gabriela; Rege, Kaushal

2015-01-01

Gene therapy is an attractive treatment option for diseases of genetic origin, including several cancers and cardiovascular diseases. While viruses are effective vectors for delivering exogenous genes to cells, concerns related to insertional mutagenesis, immunogenicity, lack of tropism, decay and high production costs necessitate the discovery of non-viral methods. Significant efforts have been focused on cationic polymers as non-viral alternatives for gene delivery. Recent studies have employed combinatorial syntheses and parallel screening methods for enhancing the efficacy of gene delivery, biocompatibility of the delivery vehicle, and overcoming cellular level barriers as they relate to polymer-mediated transgene uptake, transport, transcription, and expression. This review summarizes and discusses recent advances in combinatorial syntheses and parallel screening of cationic polymer libraries for the discovery of efficient and safe gene delivery systems. PMID:21843141

Molecular Networking As a Drug Discovery, Drug Metabolism, and Precision Medicine Strategy.

Science.gov (United States)

Quinn, Robert A; Nothias, Louis-Felix; Vining, Oliver; Meehan, Michael; Esquenazi, Eduardo; Dorrestein, Pieter C

2017-02-01

Molecular networking is a tandem mass spectrometry (MS/MS) data organizational approach that has been recently introduced in the drug discovery, metabolomics, and medical fields. The chemistry of molecules dictates how they will be fragmented by MS/MS in the gas phase and, therefore, two related molecules are likely to display similar fragment ion spectra. Molecular networking organizes the MS/MS data as a relational spectral network thereby mapping the chemistry that was detected in an MS/MS-based metabolomics experiment. Although the wider utility of molecular networking is just beginning to be recognized, in this review we highlight the principles behind molecular networking and its use for the discovery of therapeutic leads, monitoring drug metabolism, clinical diagnostics, and emerging applications in precision medicine. Copyright © 2016. Published by Elsevier Ltd.

Effects of dynamic-range compression on temporal acuity

DEFF Research Database (Denmark)

Wiinberg, Alan; Jepsen, Morten Løve; Epp, Bastian

2016-01-01

Some of the challenges that hearing-aid listeners experience with speech perception in complex acoustic environments may originate from limitations in the temporal processing of sounds. To systematically investigate the influence of hearing impairment and hearing-aid signal processing on temporal...... processing, temporal modulation transfer functions (TMTFs) and “supra-threshold” modulation-depth discrimination (MDD) thresholds were obtained in normal-hearing (NH) and hearing-impaired (HI) listeners with and without wide-dynamic range compression (WDRC). The TMTFs were obtained using tonal carriers of 1...... with the physical compression of the modulation depth due to the WDRC. Indications of reduced temporal resolution in the HI listeners were observed in the TMTF patterns for the 5 kHz carrier. Significantly higher MDD thresholds were found for the HI group relative to the NH group. No relationship was found between...

Spatio-Temporal Data Construction

Directory of Open Access Journals (Sweden)

Hai Ha Le

2013-08-01

Full Text Available On the route to a spatio-temporal geoscience information system, an appropriate data model for geo-objects in space and time has been developed. In this model, geo-objects are represented as sequences of geometries and properties with continuous evolution in each time interval. Because geomodeling software systems usually model objects at specific time instances, we want to interpolate the geometry and properties from two models of an object with only geometrical constraints (no physical or mechanical constraints. This process is called spatio-temporal data construction or morphological interpolation of intermediate geometries. This paper is strictly related to shape morphing, shape deformation, cross-parameterization and compatible remeshing and is only concerned with geological surfaces. In this study, two main sub-solutions construct compatible meshes and find trajectories in which vertices of the mesh evolve. This research aims to find an algorithm to construct spatio-temporal data with some constraints from the geosciences, such as cutting surfaces by faulting or fracturing phenomena and evolving boundaries attached to other surfaces. Another goal of this research is the implementation of the algorithm in a software product, namely a gOcad plug-in. The four main procedures of the algorithm are cutting the surfaces, setting up constraints, partitioning and calculating the parameterizations and trajectories. The software has been tested to construct data for a salt dome and other surfaces in regard to the geological processes of faulting, deposition and erosion. The result of this research is an algorithm and software for the construction of spatio-temporal data.

Discovery and first models of the quadruply lensed quasar SDSS J1433+6007

Science.gov (United States)

Agnello, Adriano; Grillo, Claudio; Jones, Tucker; Treu, Tommaso; Bonamigo, Mario; Suyu, Sherry H.

2018-03-01

We report the discovery of the quadruply lensed quasar SDSS J1433+6007 (RA = 14:33:22.8, Dec. = +60:07:13.44), mined in the SDSS DR12 photometric catalogues using a novel outlier-selection technique, without prior spectroscopic or ultraviolet excess information. Discovery data obtained at the Nordic Optical Telescope (La Palma) show nearly identical quasar spectra at zs = 2.737 ± 0.003 and four quasar images in a fold configuration, one of which sits on a blue arc, with maximum separation 3.6 arcsec. The deflector redshift is zl = 0.407 ± 0.002, from Keck-ESI spectra. We describe the selection procedure, discovery and follow-up, image positions and BVRi magnitudes, and first results and forecasts from lens model fit to the relative image positions.

Book Review: Dispute Resolution and e-Discovery

Directory of Open Access Journals (Sweden)

Milton Luoma

2012-09-01

Full Text Available Garrie, D.B., & Griver, Y.M., Eds. (2012. Dispute Resolution and e-Discovery. Thomson Reuters Westlaw, 570 pages, ISBN-13: 9780314604484, US$149.00.Reviewed by Milton Luoma, JD, (Milt.Luoma@metrostate.eduAs is apparent from its title, this book tackles two very current and difficult legal issues – electronic discovery and dispute resolution. The authors tie the two legal concepts together in an effort to provide litigants and practitioners a less expensive and less time consuming alternative than is typically the case with traditional litigation and court proceedings. By including electronic discovery in the discussions, the authors recognize the importance and significance of electronic discovery in mediation and arbitration as it is in traditional litigation.(see PDF for full review

Dreams and the temporality of consciousness.

Science.gov (United States)

MacDuffie, Katherine; Mashour, George A

2010-01-01

Understanding dreams has long been considered fundamental to the development of a theory of consciousness. Evidence from neurobiology and neuroimaging research has paved the way for new theories of dreaming that are empirically supported. In this article we argue that dreaming is a unique state of consciousness that incorporates 3 temporal dimensions: experience of the present, processing of the past, and preparation for the future. The temporal complexity of dreams is made possible in part by the unique neurobiological environment of sleep, in which stimuli are internally generated and many of the restrictions associated with waking thought are absent. Because dream consciousness is not determined by sensory stimuli, a flexible integration of past experiences and the forging of novel connections are possible. We argue that disparate dream theories may not be mutually exclusive but rather relate to different temporal domains of the dream state.

Characteristics of attention-related body sensations. Temporal stability and associations with measures of body focus, affect, sustained attention, and heart rate variability.

Science.gov (United States)

Tihanyi, Benedek T; Ferentzi, Eszter; Köteles, Ferenc

2017-09-01

This study investigated the temporal stability and correlates of attention-related body sensations that emerge without external stimulation during rest and due to focused attention on a body part. To assess attention-related body sensations, participants were asked to focus on a freely chosen body area with closed eyes, and had to report whether the sensation of that area had changed. Self-report questionnaires were used to assess various aspects of body focus (body awareness, body responsiveness, somatosensory amplification, subjective somatic symptoms), and positive and negative affectivity. Previous experiences in body-mind therapies were also measured. PEBL Continuous Performance Test was used to assess sustained attention. Heart rate variability scores were based on a 3-minute long resting heart rate measurement. Fifty-eight university students (22.3 ± 3.95 years; 34 females) participated in the study. The stability of attention-related body sensations was measured 8 weeks later on a randomly chosen sub-group (n = 28). Attention-related body sensations showed a mediocre temporal stability (r ρ  = 0.47, p = 0.012). People reporting attention-related body sensations showed significantly higher body awareness, somatosensory amplification, and resting heart rate; and marginally higher somatic symptoms. No relation was found with body-mind practice, body responsiveness, positive and negative affect, the vagal component of heart rate variability, and performance in the sustained attention task. Attention-related sensations are relatively stable over time. They are connected to some, but not to all of the aspects of body focus. Further studies are needed to elaborate the influencing stable and situational factors.