Estimating repetitive spatiotemporal patterns from resting-state brain activity data.

PubMed

Takeda, Yusuke; Hiroe, Nobuo; Yamashita, Okito; Sato, Masa-Aki

2016-06-01

Repetitive spatiotemporal patterns in spontaneous brain activities have been widely examined in non-human studies. These studies have reported that such patterns reflect past experiences embedded in neural circuits. In human magnetoencephalography (MEG) and electroencephalography (EEG) studies, however, spatiotemporal patterns in resting-state brain activities have not been extensively examined. This is because estimating spatiotemporal patterns from resting-state MEG/EEG data is difficult due to their unknown onsets. Here, we propose a method to estimate repetitive spatiotemporal patterns from resting-state brain activity data, including MEG/EEG. Without the information of onsets, the proposed method can estimate several spatiotemporal patterns, even if they are overlapping. We verified the performance of the method by detailed simulation tests. Furthermore, we examined whether the proposed method could estimate the visual evoked magnetic fields (VEFs) without using stimulus onset information. The proposed method successfully detected the stimulus onsets and estimated the VEFs, implying the applicability of this method to real MEG data. The proposed method was applied to resting-state functional magnetic resonance imaging (fMRI) data and MEG data. The results revealed informative spatiotemporal patterns representing consecutive brain activities that dynamically change with time. Using this method, it is possible to reveal discrete events spontaneously occurring in our brains, such as memory retrieval. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Understanding human activity patterns based on space-time-semantics

NASA Astrophysics Data System (ADS)

Huang, Wei; Li, Songnian

2016-11-01

Understanding human activity patterns plays a key role in various applications in an urban environment, such as transportation planning and traffic forecasting, urban planning, public health and safety, and emergency response. Most existing studies in modeling human activity patterns mainly focus on spatiotemporal dimensions, which lacks consideration of underlying semantic context. In fact, what people do and discuss at some places, inferring what is happening at the places, cannot be simple neglected because it is the root of human mobility patterns. We believe that the geo-tagged semantic context, representing what individuals do and discuss at a place and a specific time, drives a formation of specific human activity pattern. In this paper, we aim to model human activity patterns not only based on space and time but also with consideration of associated semantics, and attempt to prove a hypothesis that similar mobility patterns may have different motivations. We develop a spatiotemporal-semantic model to quantitatively express human activity patterns based on topic models, leading to an analysis of space, time and semantics. A case study is conducted using Twitter data in Toronto based on our model. Through computing the similarities between users in terms of spatiotemporal pattern, semantic pattern and spatiotemporal-semantic pattern, we find that only a small number of users (2.72%) have very similar activity patterns, while the majority (87.14%) show different activity patterns (i.e., similar spatiotemporal patterns and different semantic patterns, similar semantic patterns and different spatiotemporal patterns, or different in both). The population of users that has very similar activity patterns is decreased by 56.41% after incorporating semantic information in the corresponding spatiotemporal patterns, which can quantitatively prove the hypothesis.

Three-dimensional characterization of tethered microspheres by total internal reflection fluorescence microscopy

NASA Technical Reports Server (NTRS)

Blumberg, Seth; Gajraj, Arivalagan; Pennington, Matthew W.; Meiners, Jens-Christian

2005-01-01

Tethered particle microscopy is a powerful tool to study the dynamics of DNA molecules and DNA-protein complexes in single-molecule experiments. We demonstrate that stroboscopic total internal reflection microscopy can be used to characterize the three-dimensional spatiotemporal motion of DNA-tethered particles. By calculating characteristic measures such as symmetry and time constants of the motion, well-formed tethers can be distinguished from defective ones for which the motion is dominated by aberrant surface effects. This improves the reliability of measurements on tether dynamics. For instance, in observations of protein-mediated DNA looping, loop formation is distinguished from adsorption and other nonspecific events.

Photoresponsive biomaterials for targeted drug delivery and 4D cell culture

NASA Astrophysics Data System (ADS)

Ruskowitz, Emily R.; Deforest, Cole A.

2018-02-01

Biological signalling is regulated through a complex and tightly choreographed interplay between cells and their extracellular matrix. The spatiotemporal control of these interactions is essential for tissue function, and disruptions to this dialogue often result in aberrant cell fate and disease. When disturbances are well understood, correct biological function can be restored through the precise introduction of therapeutics. Moreover, model systems with modifiable physiochemical properties are needed to probe the effects of therapeutic molecules and to investigate cell-matrix interactions. Photoresponsive biomaterials benefit from spatiotemporal tunability, which allows for site-specific therapeutic delivery in vivo and 4D modulation of synthetic cell culture platforms to mimic the dynamic heterogeneity of the human body in vitro. In this Review, we discuss how light can be exploited to modify different biomaterials in the context of photomediated drug delivery and phototunable cell culture platforms. We survey various photochemistries for their applicability in vitro and in vivo and for the biochemical and biophysical modification of materials. Finally, we highlight emerging tools and provide an outlook for the field of photoresponsive biomaterials.

Time-Resolved and Spatio-Temporal Analysis of Complex Cognitive Processes and their Role in Disorders like Developmental Dyscalculia

PubMed Central

Mórocz, István Akos; Janoos, Firdaus; van Gelderen, Peter; Manor, David; Karni, Avi; Breznitz, Zvia; von Aster, Michael; Kushnir, Tammar; Shalev, Ruth

2012-01-01

The aim of this article is to report on the importance and challenges of a time-resolved and spatio-temporal analysis of fMRI data from complex cognitive processes and associated disorders using a study on developmental dyscalculia (DD). Participants underwent fMRI while judging the incorrectness of multiplication results, and the data were analyzed using a sequence of methods, each of which progressively provided more a detailed picture of the spatio-temporal aspect of this disease. Healthy subjects and subjects with DD performed alike behaviorally though they exhibited parietal disparities using traditional voxel-based group analyses. Further and more detailed differences, however, surfaced with a time-resolved examination of the neural responses during the experiment. While performing inter-group comparisons, a third group of subjects with dyslexia (DL) but with no arithmetic difficulties was included to test the specificity of the analysis and strengthen the statistical base with overall fifty-eight subjects. Surprisingly, the analysis showed a functional dissimilarity during an initial reading phase for the group of dyslexic but otherwise normal subjects, with respect to controls, even though only numerical digits and no alphabetic characters were presented. Thus our results suggest that time-resolved multi-variate analysis of complex experimental paradigms has the ability to yield powerful new clinical insights about abnormal brain function. Similarly, a detailed compilation of aberrations in the functional cascade may have much greater potential to delineate the core processing problems in mental disorders. PMID:22368322

Schizotypal Perceptual Aberrations of Time: Correlation between Score, Behavior and Brain Activity

PubMed Central

Arzy, Shahar; Mohr, Christine; Molnar-Szakacs, Istvan; Blanke, Olaf

2011-01-01

A fundamental trait of the human self is its continuum experience of space and time. Perceptual aberrations of this spatial and temporal continuity is a major characteristic of schizophrenia spectrum disturbances – including schizophrenia, schizotypal personality disorder and schizotypy. We have previously found the classical Perceptual Aberration Scale (PAS) scores, related to body and space, to be positively correlated with both behavior and temporo-parietal activation in healthy participants performing a task involving self-projection in space. However, not much is known about the relationship between temporal perceptual aberration, behavior and brain activity. To this aim, we composed a temporal Perceptual Aberration Scale (tPAS) similar to the traditional PAS. Testing on 170 participants suggested similar performance for PAS and tPAS. We then correlated tPAS and PAS scores to participants' performance and neural activity in a task of self-projection in time. tPAS scores correlated positively with reaction times across task conditions, as did PAS scores. Evoked potential mapping and electrical neuroimaging showed self-projection in time to recruit a network of brain regions at the left anterior temporal cortex, right temporo-parietal junction, and occipito-temporal cortex, and duration of activation in this network positively correlated with tPAS and PAS scores. These data demonstrate that schizotypal perceptual aberrations of both time and space, as reflected by tPAS and PAS scores, are positively correlated with performance and brain activation during self-projection in time in healthy individuals along the schizophrenia spectrum. PMID:21267456

Dynamic localization of Mps1 kinase to kinetochores is essential for accurate spindle microtubule attachment

PubMed Central

Dou, Zhen; Liu, Xing; Wang, Wenwen; Zhu, Tongge; Wang, Xinghui; Xu, Leilei; Abrieu, Ariane; Fu, Chuanhai; Hill, Donald L.; Yao, Xuebiao

2015-01-01

The spindle assembly checkpoint (SAC) is a conserved signaling pathway that monitors faithful chromosome segregation during mitosis. As a core component of SAC, the evolutionarily conserved kinase monopolar spindle 1 (Mps1) has been implicated in regulating chromosome alignment, but the underlying molecular mechanism remains unclear. Our molecular delineation of Mps1 activity in SAC led to discovery of a previously unidentified structural determinant underlying Mps1 function at the kinetochores. Here, we show that Mps1 contains an internal region for kinetochore localization (IRK) adjacent to the tetratricopeptide repeat domain. Importantly, the IRK region determines the kinetochore localization of inactive Mps1, and an accumulation of inactive Mps1 perturbs accurate chromosome alignment and mitotic progression. Mechanistically, the IRK region binds to the nuclear division cycle 80 complex (Ndc80C), and accumulation of inactive Mps1 at the kinetochores prevents a dynamic interaction between Ndc80C and spindle microtubules (MTs), resulting in an aberrant kinetochore attachment. Thus, our results present a previously undefined mechanism by which Mps1 functions in chromosome alignment by orchestrating Ndc80C–MT interactions and highlight the importance of the precise spatiotemporal regulation of Mps1 kinase activity and kinetochore localization in accurate mitotic progression. PMID:26240331

Dynamic localization of Mps1 kinase to kinetochores is essential for accurate spindle microtubule attachment.

PubMed

Dou, Zhen; Liu, Xing; Wang, Wenwen; Zhu, Tongge; Wang, Xinghui; Xu, Leilei; Abrieu, Ariane; Fu, Chuanhai; Hill, Donald L; Yao, Xuebiao

2015-08-18

The spindle assembly checkpoint (SAC) is a conserved signaling pathway that monitors faithful chromosome segregation during mitosis. As a core component of SAC, the evolutionarily conserved kinase monopolar spindle 1 (Mps1) has been implicated in regulating chromosome alignment, but the underlying molecular mechanism remains unclear. Our molecular delineation of Mps1 activity in SAC led to discovery of a previously unidentified structural determinant underlying Mps1 function at the kinetochores. Here, we show that Mps1 contains an internal region for kinetochore localization (IRK) adjacent to the tetratricopeptide repeat domain. Importantly, the IRK region determines the kinetochore localization of inactive Mps1, and an accumulation of inactive Mps1 perturbs accurate chromosome alignment and mitotic progression. Mechanistically, the IRK region binds to the nuclear division cycle 80 complex (Ndc80C), and accumulation of inactive Mps1 at the kinetochores prevents a dynamic interaction between Ndc80C and spindle microtubules (MTs), resulting in an aberrant kinetochore attachment. Thus, our results present a previously undefined mechanism by which Mps1 functions in chromosome alignment by orchestrating Ndc80C-MT interactions and highlight the importance of the precise spatiotemporal regulation of Mps1 kinase activity and kinetochore localization in accurate mitotic progression.

Abnormal resting-state connectivity of motor and cognitive networks in early manifest Huntington's disease.

PubMed

Wolf, R C; Sambataro, F; Vasic, N; Depping, M S; Thomann, P A; Landwehrmeyer, G B; Süssmuth, S D; Orth, M

2014-11-01

Functional magnetic resonance imaging (fMRI) of multiple neural networks during the brain's 'resting state' could facilitate biomarker development in patients with Huntington's disease (HD) and may provide new insights into the relationship between neural dysfunction and clinical symptoms. To date, however, very few studies have examined the functional integrity of multiple resting state networks (RSNs) in manifest HD, and even less is known about whether concomitant brain atrophy affects neural activity in patients. Using MRI, we investigated brain structure and RSN function in patients with early HD (n = 20) and healthy controls (n = 20). For resting-state fMRI data a group-independent component analysis identified spatiotemporally distinct patterns of motor and prefrontal RSNs of interest. We used voxel-based morphometry to assess regional brain atrophy, and 'biological parametric mapping' analyses to investigate the impact of atrophy on neural activity. Compared with controls, patients showed connectivity changes within distinct neural systems including lateral prefrontal, supplementary motor, thalamic, cingulate, temporal and parietal regions. In patients, supplementary motor area and cingulate cortex connectivity indices were associated with measures of motor function, whereas lateral prefrontal connectivity was associated with cognition. This study provides evidence for aberrant connectivity of RSNs associated with motor function and cognition in early manifest HD when controlling for brain atrophy. This suggests clinically relevant changes of RSN activity in the presence of HD-associated cortical and subcortical structural abnormalities.

Crossed wires: 3D genome misfolding in human disease.

PubMed

Norton, Heidi K; Phillips-Cremins, Jennifer E

2017-11-06

Mammalian genomes are folded into unique topological structures that undergo precise spatiotemporal restructuring during healthy development. Here, we highlight recent advances in our understanding of how the genome folds inside the 3D nucleus and how these folding patterns are miswired during the onset and progression of mammalian disease states. We discuss potential mechanisms underlying the link among genome misfolding, genome dysregulation, and aberrant cellular phenotypes. We also discuss cases in which the endogenous 3D genome configurations in healthy cells might be particularly susceptible to mutation or translocation. Together, these data support an emerging model in which genome folding and misfolding is critically linked to the onset and progression of a broad range of human diseases. © 2017 Norton and Phillips-Cremins.

Visual pattern recognition based on spatio-temporal patterns of retinal ganglion cells’ activities

PubMed Central

Jing, Wei; Liu, Wen-Zhong; Gong, Xin-Wei; Gong, Hai-Qing

2010-01-01

Neural information is processed based on integrated activities of relevant neurons. Concerted population activity is one of the important ways for retinal ganglion cells to efficiently organize and process visual information. In the present study, the spike activities of bullfrog retinal ganglion cells in response to three different visual patterns (checker-board, vertical gratings and horizontal gratings) were recorded using multi-electrode arrays. A measurement of subsequence distribution discrepancy (MSDD) was applied to identify the spatio-temporal patterns of retinal ganglion cells’ activities in response to different stimulation patterns. The results show that the population activity patterns were different in response to different stimulation patterns, such difference in activity pattern was consistently detectable even when visual adaptation occurred during repeated experimental trials. Therefore, the stimulus pattern can be reliably discriminated according to the spatio-temporal pattern of the neuronal activities calculated using the MSDD algorithm. PMID:21886670

Spatio-temporal Organization During Ventricular Fibrillation in the Human Heart.

PubMed

Robson, Jinny; Aram, Parham; Nash, Martyn P; Bradley, Chris P; Hayward, Martin; Paterson, David J; Taggart, Peter; Clayton, Richard H; Kadirkamanathan, Visakan

2018-06-01

In this paper, we present a novel approach to quantify the spatio-temporal organization of electrical activation during human ventricular fibrillation (VF). We propose three different methods based on correlation analysis, graph theoretical measures and hierarchical clustering. Using the proposed approach, we quantified the level of spatio-temporal organization during three episodes of VF in ten patients, recorded using multi-electrode epicardial recordings with 30 s coronary perfusion, 150 s global myocardial ischaemia and 30 s reflow. Our findings show a steady decline in spatio-temporal organization from the onset of VF with coronary perfusion. We observed transient increases in spatio-temporal organization during global myocardial ischaemia. However, the decline in spatio-temporal organization continued during reflow. Our results were consistent across all patients, and were consistent with the numbers of phase singularities. Our findings show that the complex spatio-temporal patterns can be studied using complex network analysis.

Different Aberrant Mentalizing Networks in Males and Females with Autism Spectrum Disorders: Evidence from Resting-State Functional Magnetic Resonance Imaging

ERIC Educational Resources Information Center

Yang, Jie; Lee, Jonathan

2018-01-01

Previous studies have found that individuals with autism spectrum disorders show impairments in mentalizing processes and aberrant brain activity compared with typically developing participants. However, the findings are mainly from male participants and the aberrant effects in autism spectrum disorder females and sex differences are still…

Phytochemicals attenuating aberrant activation of ß-catenin in cancer cells

USDA-ARS?s Scientific Manuscript database

Phytochemicals are a rich source of chemoprevention agents but their effects on modulating the Wnt/ß-catenin signaling pathway have remained largely uninvestigated. Aberrantly activated Wnt signaling can result in the abnormal stabilization of ß-catenin, a key causative step in a broad spectrum of c...

Differentiated Effects of Sensory Activities as Abolishing Operations via Non-Contingent Reinforcement on Academic and Aberrant Behavior

ERIC Educational Resources Information Center

Mancil, G. Richmond; Haydon, Todd; Boman, Marty

2016-01-01

The purpose of the study was to evaluate the effectiveness of sensory activities used as antecedent interventions on the percentage correct on academic tasks and rate of aberrant behavior in three elementary aged children with Autism Spectrum Disorders (ASD). Study activities were conducted in an after school program for children with ASD where…

Human aberrant crypt foci with carcinoma in situ from a patient with sporadic colon cancer.

PubMed

Konstantakos, A K; Siu, I M; Pretlow, T G; Stellato, T A; Pretlow, T P

1996-09-01

Aberrant crypt foci are putative preneoplastic lesions found in the colons of carcinogen-treated rodents and at an increased frequency in humans at increased risk for colon cancer. There is a strong association between aberrant crypt foci and colon cancer, including many shared phenotypic and genetic alterations. The aim of this study is to present further evidence of a relationship between aberrant crypt foci and colon cancer in humans. Multiple aberrant crypt foci from a single patient were identified in unembedded colonic mucosa. Histological sections of the aberrant crypt foci and adjacent mucosa were evaluated for dysplasia, proliferative activity, and pigment-laden macrophages that were characterized with histochemical techniques. The first patient with sporadic colon cancer identified with aberrant crypt foci with carcinoma in situ is described. It is interesting that this 99-year-old patient had multiple carcinomas in situ, pseudomelanosis coli, and two metachronous colon cancers. These data lend support to the hypothesis that aberrant crypt foci are precursors of some colon cancers.

Hotspots of aberrant enhancer activity punctuate the colorectal cancer epigenome

PubMed Central

Cohen, Andrea J.; Saiakhova, Alina; Corradin, Olivia; Luppino, Jennifer M.; Lovrenert, Katreya; Bartels, Cynthia F.; Morrow, James J.; Mack, Stephen C.; Dhillon, Gursimran; Beard, Lydia; Myeroff, Lois; Kalady, Matthew F.; Willis, Joseph; Bradner, James E.; Keri, Ruth A.; Berger, Nathan A.; Pruett-Miller, Shondra M.; Markowitz, Sanford D.; Scacheri, Peter C.

2017-01-01

In addition to mutations in genes, aberrant enhancer element activity at non-coding regions of the genome is a key driver of tumorigenesis. Here, we perform epigenomic enhancer profiling of a cohort of more than forty genetically diverse human colorectal cancer (CRC) specimens. Using normal colonic crypt epithelium as a comparator, we identify enhancers with recurrently gained or lost activity across CRC specimens. Of the enhancers highly recurrently activated in CRC, most are constituents of super enhancers, are occupied by AP-1 and cohesin complex members, and originate from primed chromatin. Many activate known oncogenes, and CRC growth can be mitigated through pharmacologic inhibition or genome editing of these loci. Nearly half of all GWAS CRC risk loci co-localize to recurrently activated enhancers. These findings indicate that the CRC epigenome is defined by highly recurrent epigenetic alterations at enhancers which activate a common, aberrant transcriptional programme critical for CRC growth and survival. PMID:28169291

Representation of Muscle Synergies in the Primate Brain.

PubMed

Overduin, Simon A; d'Avella, Andrea; Roh, Jinsook; Carmena, Jose M; Bizzi, Emilio

2015-09-16

Evidence suggests that the CNS uses motor primitives to simplify movement control, but whether it actually stores primitives instead of computing solutions on the fly to satisfy task demands is a controversial and still-unanswered possibility. Also in contention is whether these primitives take the form of time-invariant muscle coactivations ("spatial" synergies) or time-varying muscle commands ("spatiotemporal" synergies). Here, we examined forelimb muscle patterns and motor cortical spiking data in rhesus macaques (Macaca mulatta) handling objects of variable shape and size. From these data, we extracted both spatiotemporal and spatial synergies using non-negative decomposition. Each spatiotemporal synergy represents a sequence of muscular or neural activations that appeared to recur frequently during the animals' behavior. Key features of the spatiotemporal synergies (including their dimensionality, timing, and amplitude modulation) were independently observed in the muscular and neural data. In addition, both at the muscular and neural levels, these spatiotemporal synergies could be readily reconstructed as sequential activations of spatial synergies (a subset of those extracted independently from the task data), suggestive of a hierarchical relationship between the two levels of synergies. The possibility that motor cortex may execute even complex skill using spatiotemporal synergies has novel implications for the design of neuroprosthetic devices, which could gain computational efficiency by adopting the discrete and low-dimensional control that these primitives imply. We studied the motor cortical and forearm muscular activity of rhesus macaques (Macaca mulatta) as they reached, grasped, and carried objects of varied shape and size. We applied non-negative matrix factorization separately to the cortical and muscular data to reduce their dimensionality to a smaller set of time-varying "spatiotemporal" synergies. Each synergy represents a sequence of cortical or muscular activity that recurred frequently during the animals' behavior. Salient features of the synergies (including their dimensionality, timing, and amplitude modulation) were observed at both the cortical and muscular levels. The possibility that the brain may execute even complex behaviors using spatiotemporal synergies has implications for neuroprosthetic algorithm design, which could become more computationally efficient by adopting the discrete and low-dimensional control that they afford. Copyright © 2015 the authors 0270-6474/15/3512615-10$15.00/0.

Decoding-Accuracy-Based Sequential Dimensionality Reduction of Spatio-Temporal Neural Activities

NASA Astrophysics Data System (ADS)

Funamizu, Akihiro; Kanzaki, Ryohei; Takahashi, Hirokazu

Performance of a brain machine interface (BMI) critically depends on selection of input data because information embedded in the neural activities is highly redundant. In addition, properly selected input data with a reduced dimension leads to improvement of decoding generalization ability and decrease of computational efforts, both of which are significant advantages for the clinical applications. In the present paper, we propose an algorithm of sequential dimensionality reduction (SDR) that effectively extracts motor/sensory related spatio-temporal neural activities. The algorithm gradually reduces input data dimension by dropping neural data spatio-temporally so as not to undermine the decoding accuracy as far as possible. Support vector machine (SVM) was used as the decoder, and tone-induced neural activities in rat auditory cortices were decoded into the test tone frequencies. SDR reduced the input data dimension to a quarter and significantly improved the accuracy of decoding of novel data. Moreover, spatio-temporal neural activity patterns selected by SDR resulted in significantly higher accuracy than high spike rate patterns or conventionally used spatial patterns. These results suggest that the proposed algorithm can improve the generalization ability and decrease the computational effort of decoding.

Spatio-temporal mapping of variation potentials in leaves of Helianthus annuus L. seedlings in situ using multi-electrode array

PubMed Central

Zhao, Dong-Jie; Wang, Zhong-Yi; Huang, Lan; Jia, Yong-Peng; Leng, John Q.

2014-01-01

Damaging thermal stimuli trigger long-lasting variation potentials (VPs) in higher plants. Owing to limitations in conventional plant electrophysiological recording techniques, recorded signals are composed of signals originating from all of the cells that are connected to an electrode. This limitation does not enable detailed spatio-temporal distributions of transmission and electrical activities in plants to be visualised. Multi-electrode array (MEA) enables the recording and imaging of dynamic spatio-temporal electrical activities in higher plants. Here, we used an 8 × 8 MEA with a polar distance of 450 μm to measure electrical activities from numerous cells simultaneously. The mapping of the data that were recorded from the MEA revealed the transfer mode of the thermally induced VPs in the leaves of Helianthus annuus L. seedlings in situ. These results suggest that MEA can enable recordings with high spatio-temporal resolution that facilitate the determination of the bioelectrical response mode of higher plants under stress. PMID:24961469

Spatio-temporal mapping of variation potentials in leaves of Helianthus annuus L. seedlings in situ using multi-electrode array.

PubMed

Zhao, Dong-Jie; Wang, Zhong-Yi; Huang, Lan; Jia, Yong-Peng; Leng, John Q

2014-06-25

Damaging thermal stimuli trigger long-lasting variation potentials (VPs) in higher plants. Owing to limitations in conventional plant electrophysiological recording techniques, recorded signals are composed of signals originating from all of the cells that are connected to an electrode. This limitation does not enable detailed spatio-temporal distributions of transmission and electrical activities in plants to be visualised. Multi-electrode array (MEA) enables the recording and imaging of dynamic spatio-temporal electrical activities in higher plants. Here, we used an 8 × 8 MEA with a polar distance of 450 μm to measure electrical activities from numerous cells simultaneously. The mapping of the data that were recorded from the MEA revealed the transfer mode of the thermally induced VPs in the leaves of Helianthus annuus L. seedlings in situ. These results suggest that MEA can enable recordings with high spatio-temporal resolution that facilitate the determination of the bioelectrical response mode of higher plants under stress.

Increased spatial granularity of left brain activation and unique age/gender signatures: a 4D frequency domain approach to cerebral lateralization at rest.

PubMed

Agcaoglu, O; Miller, R; Mayer, A R; Hugdahl, K; Calhoun, V D

2016-12-01

Cerebral lateralization is a well-studied topic. However, most of the research to date in functional magnetic resonance imaging (fMRI) has been carried out on hemodynamic fluctuations of voxels, networks, or regions of interest (ROIs). For example, cerebral differences can be revealed by comparing the temporal activation of an ROI in one hemisphere with the corresponding homotopic region in the other hemisphere. While this approach can reveal significant information about cerebral organization, it does not provide information about the full spatiotemporal organization of the hemispheres. The cerebral differences revealed in literature suggest that hemispheres have different spatiotemporal organization in the resting state. In this study, we evaluate cerebral lateralization in the 4D spatiotemporal frequency domain to compare the hemispheres in the context of general activation patterns at different spatial and temporal scales. We use a gender-balanced resting fMRI dataset comprising over 600 healthy subjects ranging in age from 12 to 71, that have previously been studied with a network specific voxel-wise and global analysis of lateralization (Agcaoglu, et al. NeuroImage, 2014). Our analysis elucidates significant differences in the spatiotemporal organization of brain activity between hemispheres, and generally more spatiotemporal fluctuation in the left hemisphere especially in the high spatial frequency bands, and more power in the right hemisphere in the low and middle spatial frequencies. Importantly, the identified effects are not visible in the context of a typical assessment of voxelwise, regional, or even global laterality, thus our study highlights the value of 4D spatiotemporal frequency domain analyses as a complementary and powerful tool for studying brain function.

Aberrant DNA Methylation in Chronic Myeloid Leukemia: Cell Fate Control, Prognosis, and Therapeutic Response.

PubMed

Behzad, Masumeh Maleki; Shahrabi, Saeid; Jaseb, Kaveh; Bertacchini, Jessika; Ketabchi, Neda; Saki, Najmaldin

2018-01-31

Chronic myeloid leukemia (CML) is a hematopoietic stem cell malignancy characterized by the expression of the BCR-ABL1 fusion gene with different chimeric transcripts. Despite the crucial impact of constitutively active tyrosine kinase in CML pathogenesis, aberrant DNA methylation of certain genes plays an important role in disease progression and the development of drug resistance. This article reviews recent findings relevant to the effect of DNA methylation pattern of regulatory genes on various cellular activities such as cell proliferation and survival, as well as cell-signaling molecules in CML. These data might contribute to defining the role of aberrant DNA methylation in disease initiation and progression. However, further studies are needed on the validation of specific aberrant methylation markers regarding the prognosis and prediction of response among the CML patients.

The significance of PTEN and AKT aberrations in pediatric T-cell acute lymphoblastic leukemia

PubMed Central

Zuurbier, Linda; Petricoin, Emanuel F.; Vuerhard, Maartje J.; Calvert, Valerie; Kooi, Clarissa; Buijs-Gladdines, Jessica G.C.A.M.; Smits, Willem K.; Sonneveld, Edwin; Veerman, Anjo J.P.; Kamps, Willem A.; Horstmann, Martin; Pieters, Rob; Meijerink, Jules P.P.

2012-01-01

Background PI3K/AKT pathway mutations are found in T-cell acute lymphoblastic leukemia, but their overall impact and associations with other genetic aberrations is unknown. PTEN mutations have been proposed as secondary mutations that follow NOTCH1-activating mutations and cause cellular resistance to γ-secretase inhibitors. Design and Methods The impact of PTEN, PI3K and AKT aberrations was studied in a genetically well-characterized pediatric T-cell leukemia patient cohort (n=146) treated on DCOG or COALL protocols. Results PTEN and AKT E17K aberrations were detected in 13% and 2% of patients, respectively. Defective PTEN-splicing was identified in incidental cases. Patients without PTEN protein but lacking exon-, splice-, promoter mutations or promoter hypermethylation were present. PTEN/AKT mutations were especially abundant in TAL- or LMO-rearranged leukemia but nearly absent in TLX3-rearranged patients (P=0.03), the opposite to that observed for NOTCH1-activating mutations. Most PTEN/AKT mutant patients either lacked NOTCH1-activating mutations (P=0.006) or had weak NOTCH1-activating mutations (P=0.011), and consequently expressed low intracellular NOTCH1, cMYC and MUSASHI levels. T-cell leukemia patients without PTEN/AKT and NOTCH1-activating mutations fared well, with a cumulative incidence of relapse of only 8% versus 35% for PTEN/AKT and/or NOTCH1-activated patients (P=0.005). Conclusions PI3K/AKT pathway aberrations are present in 18% of pediatric T-cell acute lymphoblastic leukemia patients. Absence of strong NOTCH1-activating mutations in these cases may explain cellular insensitivity to γ-secretase inhibitors. PMID:22491738

Digital adaptive optics confocal microscopy based on iterative retrieval of optical aberration from a guidestar hologram

PubMed Central

Liu, Changgeng; Thapa, Damber; Yao, Xincheng

2017-01-01

Guidestar hologram based digital adaptive optics (DAO) is one recently emerging active imaging modality. It records each complex distorted line field reflected or scattered from the sample by an off-axis digital hologram, measures the optical aberration from a separate off-axis digital guidestar hologram, and removes the optical aberration from the distorted line fields by numerical processing. In previously demonstrated DAO systems, the optical aberration was directly retrieved from the guidestar hologram by taking its Fourier transform and extracting the phase term. For the direct retrieval method (DRM), when the sample is not coincident with the guidestar focal plane, the accuracy of the optical aberration retrieved by DRM undergoes a fast decay, leading to quality deterioration of corrected images. To tackle this problem, we explore here an image metrics-based iterative method (MIM) to retrieve the optical aberration from the guidestar hologram. Using an aberrated objective lens and scattering samples, we demonstrate that MIM can improve the accuracy of the retrieved aberrations from both focused and defocused guidestar holograms, compared to DRM, to improve the robustness of the DAO. PMID:28380937

A photocleavable rapamycin conjugate for spatiotemporal control of small GTPase activity.

PubMed

Umeda, Nobuhiro; Ueno, Tasuku; Pohlmeyer, Christopher; Nagano, Tetsuo; Inoue, Takanari

2011-01-12

We developed a novel method to spatiotemporally control the activity of signaling molecules. A newly synthesized photocaged rapamycin derivative induced rapid dimerization of FKBP (FK-506 binding protein) and FRB (FKBP-rapamycin binding protein) upon UV irradiation. With this system and the spatially confined UV irradiation, we achieved subcellularly localized activation of Rac, a member of small GTPases. Our technique offers a powerful approach to studies of dynamic intracellular signaling events.

Measurement of wavefront aberrations in cortex and peripheral nerve using a two-photon excitation guidestar

NASA Astrophysics Data System (ADS)

Futia, Gregory L.; Fontaine, Arjun; McCullough, Connor; Ozbay, Baris N.; George, Nickolas M.; Caldwell, John; Restrepo, Diego; Weir, Richard; Gibson, Emily A.

2018-02-01

Neural-machine interfaces using optogenetics are of interest due to their minimal invasiveness and potential for parallel read in and read out of activity. One possible biological target for such an interface is the peripheral nerve, where axonlevel imaging or stimulation could greatly improve interfacing with artificial limbs or enable neuron/fascicle level neuromodulation in the vagus nerve. Two-photon imaging has been successful in imaging brain activity using genetically encoded calcium or voltage indicators, but in the peripheral nerve, this is severely limited by scattering and aberrations from myelin. We employ a Shack-Hartman wavefront sensor and two-photon excitation guidestar to quantify optical scattering and aberrations in peripheral nerves and cortex. The sciatic and vagus nerves, and cortex from a ChAT-Cre ChR-eYFP transgenic mouse were excised and imaged directly. In peripheral nerves, defocus was the strongest aberration followed by astigmatism and coma. Peripheral nerve had orders of magnitude higher aberration compared with cortex. These results point to the potential of adaptive optics for increasing the depth of two-photon access into peripheral nerves.

Imaging the Spatio-Temporal Dynamics of Supragranular Activity in the Rat Somatosensory Cortex in Response to Stimulation of the Paws

PubMed Central

Morales-Botello, M. L.; Aguilar, J.; Foffani, G.

2012-01-01

We employed voltage-sensitive dye (VSD) imaging to investigate the spatio-temporal dynamics of the responses of the supragranular somatosensory cortex to stimulation of the four paws in urethane-anesthetized rats. We obtained the following main results. (1) Stimulation of the contralateral forepaw evoked VSD responses with greater amplitude and smaller latency than stimulation of the contralateral hindpaw, and ipsilateral VSD responses had a lower amplitude and greater latency than contralateral responses. (2) While the contralateral stimulation initially activated only one focus, the ipsilateral stimulation initially activated two foci: one focus was typically medial to the focus activated by contralateral stimulation and was stereotaxically localized in the motor cortex; the other focus was typically posterior to the focus activated by contralateral stimulation and was stereotaxically localized in the somatosensory cortex. (3) Forepaw and hindpaw somatosensory stimuli activated large areas of the sensorimotor cortex, well beyond the forepaw and hindpaw somatosensory areas of classical somatotopic maps, and forepaw stimuli activated larger cortical areas with greater activation velocity than hindpaw stimuli. (4) Stimulation of the forepaw and hindpaw evoked different cortical activation dynamics: forepaw responses displayed a clear medial directionality, whereas hindpaw responses were much more uniform in all directions. In conclusion, this work offers a complete spatio-temporal map of the supragranular VSD cortical activation in response to stimulation of the paws, showing important somatotopic differences between contralateral and ipsilateral maps as well as differences in the spatio-temporal activation dynamics in response to forepaw and hindpaw stimuli. PMID:22829873

Tandem duplication dup(X)(q13q22) in a male proband inherited from the mother showing mosaicism of X-inactivation.

PubMed

Steinbach, P; Horstmann, W; Scholz, W

1980-01-01

An aberrant X chromosome containing extra material in the long arm was observed in a psychomotoric retarded boy and his healthy, short-statured mother. The proband showed generalized muscular hypotony, growth retardation, and somatic anomalies including hypoplastic genitalia and cryptorchism. Chromosomal banding techniques suggested a tandem duplication of the segment Xq13 leads to Xq22. In the mother the vast majority of lymphocytes showed late replication of the aberrant X chromosome. Some of her cells, however, contained an apparently active aberrant X. Both the early- and late-replicating aberrant X exhibited late replication patterns very similar to those described for normal X chromosomes in lymphocytes. Asynchrony of DNA replication among the two segments Xq13 leads to Xq22 in the dup(X) was never observed. We consider that the clinical picture of the proband is caused by an excess of active X material.

Splicing regulation and dysregulation of cholinergic genes expressed at the neuromuscular junction.

PubMed

Ohno, Kinji; Rahman, Mohammad Alinoor; Nazim, Mohammad; Nasrin, Farhana; Lin, Yingni; Takeda, Jun-Ichi; Masuda, Akio

2017-08-01

We humans have evolved by acquiring diversity of alternative RNA metabolisms including alternative means of splicing and transcribing non-coding genes, and not by acquiring new coding genes. Tissue-specific and developmental stage-specific alternative RNA splicing is achieved by tightly regulated spatiotemporal regulation of expressions and activations of RNA-binding proteins that recognize their cognate splicing cis-elements on nascent RNA transcripts. Genes expressed at the neuromuscular junction are also alternatively spliced. In addition, germline mutations provoke aberrant splicing by compromising binding of RNA-binding proteins, and cause congenital myasthenic syndromes (CMS). We present physiological splicing mechanisms of genes for agrin (AGRN), acetylcholinesterase (ACHE), MuSK (MUSK), acetylcholine receptor (AChR) α1 subunit (CHRNA1), and collagen Q (COLQ) in human, and their aberration in diseases. Splicing isoforms of AChE T , AChE H , and AChE R are generated by hnRNP H/F. Skipping of MUSK exon 10 makes a Wnt-insensitive MuSK isoform, which is unique to human. Skipping of exon 10 is achieved by coordinated binding of hnRNP C, YB-1, and hnRNP L to exon 10. Exon P3A of CHRNA1 is alternatively included to generate a non-functional AChR α1 subunit in human. Molecular dissection of splicing mutations in patients with CMS reveals that exon P3A is alternatively skipped by hnRNP H, polypyrimidine tract-binding protein 1, and hnRNP L. Similarly, analysis of an exonic mutation in COLQ exon 16 in a CMS patient discloses that constitutive splicing of exon 16 requires binding of serine arginine-rich splicing factor 1. Intronic and exonic splicing mutations in CMS enable us to dissect molecular mechanisms underlying alternative and constitutive splicing of genes expressed at the neuromuscular junction. This is an article for the special issue XVth International Symposium on Cholinergic Mechanisms. © 2017 International Society for Neurochemistry.

Exploiting differential RNA splicing patterns: a potential new group of therapeutic targets in cancer.

PubMed

Jyotsana, Nidhi; Heuser, Michael

2018-02-01

Mutations in genes associated with splicing have been found in hematologic malignancies, but also in solid cancers. Aberrant cancer specific RNA splicing either results from mutations or misexpression of the spliceosome genes directly, or from mutations in splice sites of oncogenes or tumor suppressors. Areas covered: In this review, we present molecular targets of aberrant splicing in various malignancies, information on existing and emerging therapeutics against such targets, and strategies for future drug development. Expert opinion: Alternative splicing is an important mechanism that controls gene expression, and hence pharmacologic and genetic control of aberrant alternative RNA splicing has been proposed as a potential therapy in cancer. To identify and validate aberrant RNA splicing patterns as therapeutic targets we need to (1) characterize the most common genetic aberrations of the spliceosome and of splice sites, (2) understand the dysregulated downstream pathways and (3) exploit in-vivo disease models of aberrant splicing. Antisense oligonucleotides show promising activity, but will benefit from improved delivery tools. Inhibitors of mutated splicing factors require improved specificity, as alternative and aberrant splicing are often intertwined like two sides of the same coin. In summary, targeting aberrant splicing is an early but emerging field in cancer treatment.

Light Controlled Modulation of Gene Expression by Chemical Optoepigenetic Probes

PubMed Central

Reis, Surya A.; Ghosh, Balaram; Hendricks, J. Adam; Szantai-Kis, D. Miklos; Törk, Lisa; Ross, Kenneth N.; Lamb, Justin; Read-Button, Willis; Zheng, Baixue; Wang, Hongtao; Salthouse, Christopher; Haggarty, Stephen J.; Mazitschek, Ralph

2016-01-01

Epigenetic gene regulation is a dynamic process orchestrated by chromatin-modifying enzymes. Many of these master regulators exert their function through covalent modification of DNA and histone proteins. Aberrant epigenetic processes have been implicated in the pathophysiology of multiple human diseases. Small-molecule inhibitors have been essential to advancing our understanding of the underlying molecular mechanisms of epigenetic processes. However, the resolution offered by small molecules is often insufficient to manipulate epigenetic processes with high spatio-temporal control. Here, we present a novel and generalizable approach, referred to as ‘Chemo-Optical Modulation of Epigenetically-regulated Transcription’ (COMET), enabling high-resolution, optical control of epigenetic mechanisms based on photochromic inhibitors of human histone deacetylases using visible light. COMET probes may translate into novel therapeutic strategies for diseases where conditional and selective epigenome modulation is required. PMID:26974814

Spatiotemporal Dynamics of Argument Retrieval and Reordering: An fMRI and EEG Study on Sentence Processing

PubMed Central

Meyer, Lars; Obleser, Jonas; Kiebel, Stefan J.; Friederici, Angela D.

2012-01-01

In sentence processing, it is still unclear how the neural language network successfully establishes argument–verb dependencies in its spatiotemporal neuronal dynamics. Previous work has suggested that the establishment of subject–verb and object–verb dependencies requires argument retrieval from working memory, and that dependency establishment in object-first sentences additionally necessitates argument reordering. We examine the spatiotemporal neuronal dynamics of the brain regions that subserve these sub-processes by crossing an argument reordering factor (i.e., subject-first versus object-first sentences) with an argument retrieval factor (i.e., short versus long argument–verb dependencies) in German. Using functional magnetic resonance imaging (fMRI), we found that reordering demands focally activate the left pars opercularis (Broca’s area), while storage and retrieval demands activated left temporo-parietal (TP) regions. In addition, when analyzing the time course of fMRI-informed equivalent current dipole sources in the EEG at the subcategorizing verb, we found that activity in the TP-region occurs relatively early (40–180 ms), followed by activity in Broca’s area (300–500 ms). These findings were matched by topographical correlation analyses of fMRI activations in EEG sensor space, showing that, in the scalp potential, TP-region activity surfaces as an early positivity and IFG activity as a later positivity in the scalp potential. These results provide fine-grained evidence for spatiotemporally separable sub-processes of argument retrieval and reordering in sentence processing. PMID:23248607

Optically triggering spatiotemporally confined GPCR activity in a cell and programming neurite initiation and extension

PubMed Central

Karunarathne, W. K. Ajith; Giri, Lopamudra; Kalyanaraman, Vani; Gautam, N.

2013-01-01

G-protein–coupled receptor (GPCR) activity gradients evoke important cell behavior but there is a dearth of methods to induce such asymmetric signaling in a cell. Here we achieved reversible, rapidly switchable patterns of spatiotemporally restricted GPCR activity in a single cell. We recruited properties of nonrhodopsin opsins—rapid deactivation, distinct spectral tuning, and resistance to bleaching—to activate native Gi, Gq, or Gs signaling in selected regions of a cell. Optical inputs were designed to spatiotemporally control levels of second messengers, IP3, phosphatidylinositol (3,4,5)-triphosphate, and cAMP in a cell. Spectrally selective imaging was accomplished to simultaneously monitor optically evoked molecular and cellular response dynamics. We show that localized optical activation of an opsin-based trigger can induce neurite initiation, phosphatidylinositol (3,4,5)-triphosphate increase, and actin remodeling. Serial optical inputs to neurite tips can refashion early neuron differentiation. Methods here can be widely applied to program GPCR-mediated cell behaviors. PMID:23479634

Multiview human activity recognition system based on spatiotemporal template for video surveillance system

NASA Astrophysics Data System (ADS)

Kushwaha, Alok Kumar Singh; Srivastava, Rajeev

2015-09-01

An efficient view invariant framework for the recognition of human activities from an input video sequence is presented. The proposed framework is composed of three consecutive modules: (i) detect and locate people by background subtraction, (ii) view invariant spatiotemporal template creation for different activities, (iii) and finally, template matching is performed for view invariant activity recognition. The foreground objects present in a scene are extracted using change detection and background modeling. The view invariant templates are constructed using the motion history images and object shape information for different human activities in a video sequence. For matching the spatiotemporal templates for various activities, the moment invariants and Mahalanobis distance are used. The proposed approach is tested successfully on our own viewpoint dataset, KTH action recognition dataset, i3DPost multiview dataset, MSR viewpoint action dataset, VideoWeb multiview dataset, and WVU multiview human action recognition dataset. From the experimental results and analysis over the chosen datasets, it is observed that the proposed framework is robust, flexible, and efficient with respect to multiple views activity recognition, scale, and phase variations.

A Biologically Constrained, Mathematical Model of Cortical Wave Propagation Preceding Seizure Termination

PubMed Central

González-Ramírez, Laura R.; Ahmed, Omar J.; Cash, Sydney S.; Wayne, C. Eugene; Kramer, Mark A.

2015-01-01

Epilepsy—the condition of recurrent, unprovoked seizures—manifests in brain voltage activity with characteristic spatiotemporal patterns. These patterns include stereotyped semi-rhythmic activity produced by aggregate neuronal populations, and organized spatiotemporal phenomena, including waves. To assess these spatiotemporal patterns, we develop a mathematical model consistent with the observed neuronal population activity and determine analytically the parameter configurations that support traveling wave solutions. We then utilize high-density local field potential data recorded in vivo from human cortex preceding seizure termination from three patients to constrain the model parameters, and propose basic mechanisms that contribute to the observed traveling waves. We conclude that a relatively simple and abstract mathematical model consisting of localized interactions between excitatory cells with slow adaptation captures the quantitative features of wave propagation observed in the human local field potential preceding seizure termination. PMID:25689136

Carpal Tunnel Syndrome in Aberrant Muscle Syndrome: A Case Report and Review of the Literature.

PubMed

Steele, Jessica; Coombs, Christopher

2018-06-01

Aberrant Muscle Syndrome (AMS) is a rare congenital hand difference that is characterised by unilateral non-progressive muscular hyperplasia. The aetiology of aberrant muscle syndrome is not known, but a recently published case has shown a somatic PIK3CA activating mutation in a patient with AMS. Carpal tunnel syndrome (CTS) in children is rare. The most common causes are the mucopolysaccaridoses but space-occupying lesions have also been reported to cause CTS in children. We report the first case of CTS in a child with AMS successfully treated with open carpal tunnel release and excision of aberrant muscles.

A System for Studying Facial Nerve Function in Rats through Simultaneous Bilateral Monitoring of Eyelid and Whisker Movements

PubMed Central

Heaton, James T.; Kowaleski, Jeffrey M.; Bermejo, Roberto; Zeigler, H. Philip; Ahlgren, David J.; Hadlock, Tessa A.

2008-01-01

The occurrence of inappropriate co-contraction of facially innervated muscles in humans (synkinesis) is a common sequela of facial nerve injury and recovery. We have developed a system for studying facial nerve function and synkinesis in restrained rats using non-contact opto-electronic techniques that enable simultaneous bilateral monitoring of eyelid and whisker movements. Whisking is monitored in high spatio-temporal resolution using laser micrometers, and eyelid movements are detected using infrared diode and phototransistor pairs that respond to the increased reflection when the eyelids cover the cornea. To validate the system, eight rats were tested with multiple five-minute sessions that included corneal air puffs to elicit blink and scented air flows to elicit robust whisking. Four rats then received unilateral facial nerve section and were tested at weeks 3–6. Whisking and eye blink behavior occurred both spontaneously and under stimulus control, with no detectable difference from published whisking data. Proximal facial nerve section caused an immediate ipsilateral loss of whisking and eye blink response, but some ocular closures emerged due to retractor bulbi muscle function. The independence observed between whisker and eyelid control indicates that this system may provide a powerful tool for identifying abnormal co-activation of facial zones resulting from aberrant axonal regeneration. PMID:18442856

Spatio-temporal manipulation of small GTPase activity at subcellular level and on timescale of seconds in living cells.

PubMed

DeRose, Robert; Pohlmeyer, Christopher; Umeda, Nobuhiro; Ueno, Tasuku; Nagano, Tetsuo; Kuo, Scot; Inoue, Takanari

2012-03-09

Dynamic regulation of the Rho family of small guanosine triphosphatases (GTPases) with great spatiotemporal precision is essential for various cellular functions and events(1, 2). Their spatiotemporally dynamic nature has been revealed by visualization of their activity and localization in real time(3). In order to gain deeper understanding of their roles in diverse cellular functions at the molecular level, the next step should be perturbation of protein activities at a precise subcellular location and timing. To achieve this goal, we have developed a method for light-induced, spatio-temporally controlled activation of small GTPases by combining two techniques: (1) rapamycin-induced FKBP-FRB heterodimerization and (2) a photo-caging method of rapamycin. With the use of rapamycin-mediated FKBP-FRB heterodimerization, we have developed a method for rapidly inducible activation or inactivation of small GTPases including Rac(4), Cdc42(4), RhoA(4) and Ras(5), in which rapamycin induces translocation of FKBP-fused GTPases, or their activators, to the plasma membrane where FRB is anchored. For coupling with this heterodimerization system, we have also developed a photo-caging system of rapamycin analogs. A photo-caged compound is a small molecule whose activity is suppressed with a photocleavable protecting group known as a caging group. To suppress heterodimerization activity completely, we designed a caged rapamycin that is tethered to a macromolecule such that the resulting large complex cannot cross the plasma membrane, leading to virtually no background activity as a chemical dimerizer inside cells(6). Figure 1 illustrates a scheme of our system. With the combination of these two systems, we locally recruited a Rac activator to the plasma membrane on a timescale of seconds and achieved light-induced Rac activation at the subcellular level(6).

The spatiotemporal pattern of Src activation at lipid rafts revealed by diffusion-corrected FRET imaging.

PubMed

Lu, Shaoying; Ouyang, Mingxing; Seong, Jihye; Zhang, Jin; Chien, Shu; Wang, Yingxiao

2008-07-25

Genetically encoded biosensors based on fluorescence resonance energy transfer (FRET) have been widely applied to visualize the molecular activity in live cells with high spatiotemporal resolution. However, the rapid diffusion of biosensor proteins hinders a precise reconstruction of the actual molecular activation map. Based on fluorescence recovery after photobleaching (FRAP) experiments, we have developed a finite element (FE) method to analyze, simulate, and subtract the diffusion effect of mobile biosensors. This method has been applied to analyze the mobility of Src FRET biosensors engineered to reside at different subcompartments in live cells. The results indicate that the Src biosensor located in the cytoplasm moves 4-8 folds faster (0.93+/-0.06 microm(2)/sec) than those anchored on different compartments in plasma membrane (at lipid raft: 0.11+/-0.01 microm(2)/sec and outside: 0.18+/-0.02 microm(2)/sec). The mobility of biosensor at lipid rafts is slower than that outside of lipid rafts and is dominated by two-dimensional diffusion. When this diffusion effect was subtracted from the FRET ratio images, high Src activity at lipid rafts was observed at clustered regions proximal to the cell periphery, which remained relatively stationary upon epidermal growth factor (EGF) stimulation. This result suggests that EGF induced a Src activation at lipid rafts with well-coordinated spatiotemporal patterns. Our FE-based method also provides an integrated platform of image analysis for studying molecular mobility and reconstructing the spatiotemporal activation maps of signaling molecules in live cells.

Dynamic performance of MEMS deformable mirrors for use in an active/adaptive two-photon microscope

NASA Astrophysics Data System (ADS)

Zhang, Christian C.; Foster, Warren B.; Downey, Ryan D.; Arrasmith, Christopher L.; Dickensheets, David L.

2016-03-01

Active optics can facilitate two-photon microscopic imaging deep in tissue. We are investigating fast focus control mirrors used in concert with an aberration correction mirror to control the axial position of focus and system aberrations dynamically during scanning. With an adaptive training step, sample-induced aberrations may be compensated as well. If sufficiently fast and precise, active optics may be able to compensate under-corrected imaging optics as well as sample aberrations to maintain diffraction-limited performance throughout the field of view. Toward this end we have measured a Boston Micromachines Corporation Multi-DM 140 element deformable mirror, and a Revibro Optics electrostatic 4-zone focus control mirror to characterize dynamic performance. Tests for the Multi-DM included both step response and sinusoidal frequency sweeps of specific Zernike modes. For the step response we measured 10%-90% rise times for the target Zernike amplitude, and wavefront rms error settling times. Frequency sweeps identified the 3dB bandwidth of the mirror when attempting to follow a sinusoidal amplitude trajectory for a specific Zernike mode. For five tested Zernike modes (defocus, spherical aberration, coma, astigmatism and trefoil) we find error settling times for mode amplitudes up to 400nm to be less than 52 us, and 3 dB frequencies range from 6.5 kHz to 10 kHz. The Revibro Optics mirror was tested for step response only, with error settling time of 80 μs for a large 3 um defocus step, and settling time of only 18 μs for a 400nm spherical aberration step. These response speeds are sufficient for intra-scan correction at scan rates typical of two-photon microscopy.

Transient spatiotemporal chaos in the Morris-Lecar neuronal ring network.

PubMed

Keplinger, Keegan; Wackerbauer, Renate

2014-03-01

Transient behavior is thought to play an integral role in brain functionality. Numerical simulations of the firing activity of diffusively coupled, excitable Morris-Lecar neurons reveal transient spatiotemporal chaos in the parameter regime below the saddle-node on invariant circle bifurcation point. The neighborhood of the chaotic saddle is reached through perturbations of the rest state, in which few initially active neurons at an effective spatial distance can initiate spatiotemporal chaos. The system escapes from the neighborhood of the chaotic saddle to either the rest state or to a state of pulse propagation. The lifetime of the chaotic transients is manipulated in a statistical sense through a singular application of a synchronous perturbation to a group of neurons.

Bilateral Activity-Dependent Interactions in the Developing Corticospinal System

PubMed Central

Friel, Kathleen M.; Martin, John H.

2009-01-01

Activity-dependent competition between the corticospinal (CS) systems in each hemisphere drives postnatal development of motor skills and stable CS tract connections with contralateral spinal motor circuits. Unilateral restriction of motor cortex (M1) activity during an early postnatal critical period impairs contralateral visually guided movements later in development and in maturity. Silenced M1 develops aberrant connections with the contralateral spinal cord whereas the initially active M1, in the other hemisphere, develops bilateral connections. In this study, we determined whether the aberrant pattern of CS tract terminations and motor impairments produced by early postnatal M1 activity restriction could be abrogated by reducing activity-dependent synaptic competition from the initially active M1 later in development. We first inactivated M1 unilaterally between postnatal weeks 5–7. We next inactivated M1 on the other side from weeks 7–11 (alternate inactivation), to reduce the competitive advantage that this side may have over the initially inactivated side. Alternate inactivation redirected aberrant contralateral CS tract terminations from the initially silenced M1 to their normal spinal territories and reduced the density of aberrant ipsilateral terminations from the initially active side. Normal movement endpoint control during visually guided locomotion was fully restored. This reorganization of CS terminals reveals an unsuspected late plasticity after the critical period for establishing the pattern of CS terminations in the spinal cord. Our findings show that robust bilateral interactions between the developing CS systems on each side are important for achieving balance between contralateral and ipsilateral CS tract connections and visuomotor control. PMID:17928450

Effects of Spatio-Temporal Aliasing on Pilot Performance in Active Control Tasks

NASA Technical Reports Server (NTRS)

Zaal, Peter; Sweet, Barbara

2010-01-01

Spatio-temporal aliasing affects pilot performance and control behavior. For increasing refresh rates: 1) Significant change in control behavior: a) Increase in visual gain and neuromuscular frequency. b) Decrease in visual time delay. 2) Increase in tracking performance: a) Decrease in RMSe. b) Increase in crossover frequency.

Cortical Spatio-Temporal Dynamics Underlying Phonological Target Detection in Humans

ERIC Educational Resources Information Center

Chang, Edward F.; Edwards, Erik; Nagarajan, Srikantan S.; Fogelson, Noa; Dalal, Sarang S.; Canolty, Ryan T.; Kirsch, Heidi E.; Barbaro, Nicholas M.; Knight, Robert T.

2011-01-01

Selective processing of task-relevant stimuli is critical for goal-directed behavior. We used electrocorticography to assess the spatio-temporal dynamics of cortical activation during a simple phonological target detection task, in which subjects press a button when a prespecified target syllable sound is heard. Simultaneous surface potential…

Active Correction of Aberrations of Low-Quality Telescope Optics

NASA Technical Reports Server (NTRS)

Hemmati, Hamid; Chen, Yijian

2007-01-01

A system of active optics that includes a wavefront sensor and a deformable mirror has been demonstrated to be an effective means of partly correcting wavefront aberrations introduced by fixed optics (lenses and mirrors) in telescopes. It is envisioned that after further development, active optics would be used to reduce wavefront aberrations of about one wave or less in telescopes having aperture diameters of the order of meters or tens of meters. Although this remaining amount of aberration would be considered excessive in scientific applications in which diffraction-limited performance is required, it would be acceptable for free-space optical- communication applications at wavelengths of the order of 1 m. To prevent misunderstanding, it is important to state the following: The technological discipline of active optics, in which the primary or secondary mirror of a telescope is directly and dynamically tilted, distorted, and/or otherwise varied to reduce wavefront aberrations, has existed for decades. The term active optics does not necessarily mean the same thing as does adaptive optics, even though active optics and adaptive optics are related. The term "adaptive optics" is often used to refer to wavefront correction at speeds characterized by frequencies ranging up to between hundreds of hertz and several kilohertz high enough to enable mitigation of adverse effects of fluctuations in atmospheric refraction upon propagation of light beams. The term active optics usually appears in reference to wavefront correction at significantly lower speeds, characterized by times ranging from about 1 second to as long as minutes. Hence, the novelty of the present development lies, not in the basic concept of active or adaptive optics, but in the envisioned application of active optics in conjunction with a deformable mirror to achieve acceptably small wavefront errors in free-space optical communication systems that include multi-meter-diameter telescope mirrors that are relatively inexpensive because their surface figures are characterized by errors as large as about 10 waves. Figure 1 schematically depicts the apparatus used in an experiment to demonstrate such an application on a reduced scale involving a 30-cm-diameter aperture.

Precise Spatiotemporal Control of Optogenetic Activation Using an Acousto-Optic Device

PubMed Central

Guo, Yanmeng; Song, Peipei; Zhang, Xiaohui; Zeng, Shaoqun; Wang, Zuoren

2011-01-01

Light activation and inactivation of neurons by optogenetic techniques has emerged as an important tool for studying neural circuit function. To achieve a high resolution, new methods are being developed to selectively manipulate the activity of individual neurons. Here, we report that the combination of an acousto-optic device (AOD) and single-photon laser was used to achieve rapid and precise spatiotemporal control of light stimulation at multiple points in a neural circuit with millisecond time resolution. The performance of this system in activating ChIEF expressed on HEK 293 cells as well as cultured neurons was first evaluated, and the laser stimulation patterns were optimized. Next, the spatiotemporally selective manipulation of multiple neurons was achieved in a precise manner. Finally, we demonstrated the versatility of this high-resolution method in dissecting neural circuits both in the mouse cortical slice and the Drosophila brain in vivo. Taken together, our results show that the combination of AOD-assisted laser stimulation and optogenetic tools provides a flexible solution for manipulating neuronal activity at high efficiency and with high temporal precision. PMID:22174813

Spatio-Temporal Progression of Cortical Activity Related to Continuous Overt and Covert Speech Production in a Reading Task.

PubMed

Brumberg, Jonathan S; Krusienski, Dean J; Chakrabarti, Shreya; Gunduz, Aysegul; Brunner, Peter; Ritaccio, Anthony L; Schalk, Gerwin

2016-01-01

How the human brain plans, executes, and monitors continuous and fluent speech has remained largely elusive. For example, previous research has defined the cortical locations most important for different aspects of speech function, but has not yet yielded a definition of the temporal progression of involvement of those locations as speech progresses either overtly or covertly. In this paper, we uncovered the spatio-temporal evolution of neuronal population-level activity related to continuous overt speech, and identified those locations that shared activity characteristics across overt and covert speech. Specifically, we asked subjects to repeat continuous sentences aloud or silently while we recorded electrical signals directly from the surface of the brain (electrocorticography (ECoG)). We then determined the relationship between cortical activity and speech output across different areas of cortex and at sub-second timescales. The results highlight a spatio-temporal progression of cortical involvement in the continuous speech process that initiates utterances in frontal-motor areas and ends with the monitoring of auditory feedback in superior temporal gyrus. Direct comparison of cortical activity related to overt versus covert conditions revealed a common network of brain regions involved in speech that may implement orthographic and phonological processing. Our results provide one of the first characterizations of the spatiotemporal electrophysiological representations of the continuous speech process, and also highlight the common neural substrate of overt and covert speech. These results thereby contribute to a refined understanding of speech functions in the human brain.

Spatio-Temporal Progression of Cortical Activity Related to Continuous Overt and Covert Speech Production in a Reading Task

PubMed Central

Brumberg, Jonathan S.; Krusienski, Dean J.; Chakrabarti, Shreya; Gunduz, Aysegul; Brunner, Peter; Ritaccio, Anthony L.; Schalk, Gerwin

2016-01-01

How the human brain plans, executes, and monitors continuous and fluent speech has remained largely elusive. For example, previous research has defined the cortical locations most important for different aspects of speech function, but has not yet yielded a definition of the temporal progression of involvement of those locations as speech progresses either overtly or covertly. In this paper, we uncovered the spatio-temporal evolution of neuronal population-level activity related to continuous overt speech, and identified those locations that shared activity characteristics across overt and covert speech. Specifically, we asked subjects to repeat continuous sentences aloud or silently while we recorded electrical signals directly from the surface of the brain (electrocorticography (ECoG)). We then determined the relationship between cortical activity and speech output across different areas of cortex and at sub-second timescales. The results highlight a spatio-temporal progression of cortical involvement in the continuous speech process that initiates utterances in frontal-motor areas and ends with the monitoring of auditory feedback in superior temporal gyrus. Direct comparison of cortical activity related to overt versus covert conditions revealed a common network of brain regions involved in speech that may implement orthographic and phonological processing. Our results provide one of the first characterizations of the spatiotemporal electrophysiological representations of the continuous speech process, and also highlight the common neural substrate of overt and covert speech. These results thereby contribute to a refined understanding of speech functions in the human brain. PMID:27875590

The spatiotemporal MEG covariance matrix modeled as a sum of Kronecker products.

PubMed

Bijma, Fetsje; de Munck, Jan C; Heethaar, Rob M

2005-08-15

The single Kronecker product (KP) model for the spatiotemporal covariance of MEG residuals is extended to a sum of Kronecker products. This sum of KP is estimated such that it approximates the spatiotemporal sample covariance best in matrix norm. Contrary to the single KP, this extension allows for describing multiple, independent phenomena in the ongoing background activity. Whereas the single KP model can be interpreted by assuming that background activity is generated by randomly distributed dipoles with certain spatial and temporal characteristics, the sum model can be physiologically interpreted by assuming a composite of such processes. Taking enough terms into account, the spatiotemporal sample covariance matrix can be described exactly by this extended model. In the estimation of the sum of KP model, it appears that the sum of the first 2 KP describes between 67% and 93%. Moreover, these first two terms describe two physiological processes in the background activity: focal, frequency-specific alpha activity, and more widespread non-frequency-specific activity. Furthermore, temporal nonstationarities due to trial-to-trial variations are not clearly visible in the first two terms, and, hence, play only a minor role in the sample covariance matrix in terms of matrix power. Considering the dipole localization, the single KP model appears to describe around 80% of the noise and seems therefore adequate. The emphasis of further improvement of localization accuracy should be on improving the source model rather than the covariance model.

On the Characterization of the Spatio-Temporal Profiles of Brain Activity Associated with Face Naming and the Tip-of-the-Tongue State: A Magnetoencephalographic (MEG) Study

ERIC Educational Resources Information Center

Lindin, Monica; Diaz, Fernando; Capilla, Almudena; Ortiz, Tomas; Maestu, Fernando

2010-01-01

The tip-of-the-tongue state (TOT) in face naming is a transient state of difficulty in access to a person's name along with the conviction that the name is known. The aim of the present study was to characterize the spatio-temporal course of brain activation in the successful naming and TOT states, by means of magnetoencephalography, during a…

Observing the cell in its native state: Imaging subcellular dynamics in multicellular organisms.

PubMed

Liu, Tsung-Li; Upadhyayula, Srigokul; Milkie, Daniel E; Singh, Ved; Wang, Kai; Swinburne, Ian A; Mosaliganti, Kishore R; Collins, Zach M; Hiscock, Tom W; Shea, Jamien; Kohrman, Abraham Q; Medwig, Taylor N; Dambournet, Daphne; Forster, Ryan; Cunniff, Brian; Ruan, Yuan; Yashiro, Hanako; Scholpp, Steffen; Meyerowitz, Elliot M; Hockemeyer, Dirk; Drubin, David G; Martin, Benjamin L; Matus, David Q; Koyama, Minoru; Megason, Sean G; Kirchhausen, Tom; Betzig, Eric

2018-04-20

True physiological imaging of subcellular dynamics requires studying cells within their parent organisms, where all the environmental cues that drive gene expression, and hence the phenotypes that we actually observe, are present. A complete understanding also requires volumetric imaging of the cell and its surroundings at high spatiotemporal resolution, without inducing undue stress on either. We combined lattice light-sheet microscopy with adaptive optics to achieve, across large multicellular volumes, noninvasive aberration-free imaging of subcellular processes, including endocytosis, organelle remodeling during mitosis, and the migration of axons, immune cells, and metastatic cancer cells in vivo. The technology reveals the phenotypic diversity within cells across different organisms and developmental stages and may offer insights into how cells harness their intrinsic variability to adapt to different physiological environments. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Combination of PCA and LORETA for sources analysis of ERP data: an emotional processing study

NASA Astrophysics Data System (ADS)

Hu, Jin; Tian, Jie; Yang, Lei; Pan, Xiaohong; Liu, Jiangang

2006-03-01

The purpose of this paper is to study spatiotemporal patterns of neuronal activity in emotional processing by analysis of ERP data. 108 pictures (categorized as positive, negative and neutral) were presented to 24 healthy, right-handed subjects while 128-channel EEG data were recorded. An analysis of two steps was applied to the ERP data. First, principal component analysis was performed to obtain significant ERP components. Then LORETA was applied to each component to localize their brain sources. The first six principal components were extracted, each of which showed different spatiotemporal patterns of neuronal activity. The results agree with other emotional study by fMRI or PET. The combination of PCA and LORETA can be used to analyze spatiotemporal patterns of ERP data in emotional processing.

Relations between Neurological Aberrations and Psychological Dysfunctions in Children with Serious Language Problems.

ERIC Educational Resources Information Center

Bo, Ola O.; And Others

1992-01-01

Relationships between neuropsychological aberrations and psychological dysfunction were studied for 20 Swedish children (average age around 10 years at first testing) with serious language problems through (1) electroencephalography; (2) brain stem response audiometry; (3) magnetic resonance imaging; and (4) brain electric activity mapping by…

Optical aberrations, retinal image quality and eye growth: Experimentation and modeling

NASA Astrophysics Data System (ADS)

Tian, Yibin

2007-12-01

Retinal image quality is important for normal eye growth. Optical aberrations are of interest for two reasons: first, they degrade retinal images; second, they might provide some cues to defocus. Higher than normal ocular aberrations have been previously associated with human myopia. However, these studies were cross-sectional in design, and only reported aberrations in terms of root mean square (RMS) errors of Zernike coefficients, a poor metric of optical quality. This dissertation presents results from investigations of ocular optical aberrations, retinal image quality and eye growth in chicks and humans. A number of techniques were utilized, including Shack-Hartmann aberrometry, high-frequency A-scan ultrasonography, ciliary nerve section (CNX), photorefractive keratectomy (PRK) as well as computer simulations and modeling. A technique to extract light scatter information from Shack-Hartmann images was also developed. The main findings of the dissertation are summarized below. In young chicks, most ocular aberrations decreased with growth in both normal and CNX eyes, and there were diurnal fluctuations in some aberrations. Modeling suggested active reduction in higher order aberrations (HOAs) during early development. Although CNX eyes manifested greater than normal HOAs, they showed near normal growth. Retinal image degradation varied greatly among individual eyes post-PRK in young chicks. Including light scatter information into analyses of retinal image quality better estimated the latter. Albino eyes showed more severe retinal image degradation than normal eyes, due to increased optical aberrations and light scatter, but their growth was similar to those of normal eyes, implying that they are relatively insensitive to retina image quality. Although the above results questioned the influence of optical aberrations on early ocular growth, some optical quality metrics, derived from optical aberrations data, could predict how much the eyes of young chicks subsequently elongated. The performance of some focus measures was very poor when non-defocus aberrations exceeded a certain level; presumably, these non-defocus aberrations might interfere with the eye's ability to interpret defocus. In anisomyopic human adults, more myopic eyes had larger anterior and vitreous chambers, greater astigmatism, and more positive spherical aberration. However, compared to isometropes, only interocular differences in spherical equivalent refractive errors were significantly increased.

Spatio-temporal Dynamics of Audiovisual Speech Processing

PubMed Central

Bernstein, Lynne E.; Auer, Edward T.; Wagner, Michael; Ponton, Curtis W.

2007-01-01

The cortical processing of auditory-alone, visual-alone, and audiovisual speech information is temporally and spatially distributed, and functional magnetic resonance imaging (fMRI) cannot adequately resolve its temporal dynamics. In order to investigate a hypothesized spatio-temporal organization for audiovisual speech processing circuits, event-related potentials (ERPs) were recorded using electroencephalography (EEG). Stimuli were congruent audiovisual /bα/, incongruent auditory /bα/ synchronized with visual /gα/, auditory-only /bα/, and visual-only /bα/ and /gα/. Current density reconstructions (CDRs) of the ERP data were computed across the latency interval of 50-250 milliseconds. The CDRs demonstrated complex spatio-temporal activation patterns that differed across stimulus conditions. The hypothesized circuit that was investigated here comprised initial integration of audiovisual speech by the middle superior temporal sulcus (STS), followed by recruitment of the intraparietal sulcus (IPS), followed by activation of Broca's area (Miller and d'Esposito, 2005). The importance of spatio-temporally sensitive measures in evaluating processing pathways was demonstrated. Results showed, strikingly, early (< 100 msec) and simultaneous activations in areas of the supramarginal and angular gyrus (SMG/AG), the IPS, the inferior frontal gyrus, and the dorsolateral prefrontal cortex. Also, emergent left hemisphere SMG/AG activation, not predicted based on the unisensory stimulus conditions was observed at approximately 160 to 220 msec. The STS was neither the earliest nor most prominent activation site, although it is frequently considered the sine qua non of audiovisual speech integration. As discussed here, the relatively late activity of the SMG/AG solely under audiovisual conditions is a possible candidate audiovisual speech integration response. PMID:17920933

Linear phase conjugation for atmospheric aberration compensation

NASA Astrophysics Data System (ADS)

Grasso, Robert J.; Stappaerts, Eddy A.

1998-01-01

Atmospheric induced aberrations can seriously degrade laser performance, greatly affecting the beam that finally reaches the target. Lasers propagated over any distance in the atmosphere suffer from a significant decrease in fluence at the target due to these aberrations. This is especially so for propagation over long distances. It is due primarily to fluctuations in the atmosphere over the propagation path, and from platform motion relative to the intended aimpoint. Also, delivery of high fluence to the target typically requires low beam divergence, thus, atmospheric turbulence, platform motion, or both results in a lack of fine aimpoint control to keep the beam directed at the target. To improve both the beam quality and amount of laser energy delivered to the target, Northrop Grumman has developed the Active Tracking System (ATS); a novel linear phase conjugation aberration compensation technique. Utilizing a silicon spatial light modulator (SLM) as a dynamic wavefront reversing element, ATS undoes aberrations induced by the atmosphere, platform motion or both. ATS continually tracks the target as well as compensates for atmospheric and platform motion induced aberrations. This results in a high fidelity, near-diffraction limited beam delivered to the target.

Similarity-Based Fusion of MEG and fMRI Reveals Spatio-Temporal Dynamics in Human Cortex During Visual Object Recognition

PubMed Central

Cichy, Radoslaw Martin; Pantazis, Dimitrios; Oliva, Aude

2016-01-01

Every human cognitive function, such as visual object recognition, is realized in a complex spatio-temporal activity pattern in the brain. Current brain imaging techniques in isolation cannot resolve the brain's spatio-temporal dynamics, because they provide either high spatial or temporal resolution but not both. To overcome this limitation, we developed an integration approach that uses representational similarities to combine measurements of magnetoencephalography (MEG) and functional magnetic resonance imaging (fMRI) to yield a spatially and temporally integrated characterization of neuronal activation. Applying this approach to 2 independent MEG–fMRI data sets, we observed that neural activity first emerged in the occipital pole at 50–80 ms, before spreading rapidly and progressively in the anterior direction along the ventral and dorsal visual streams. Further region-of-interest analyses established that dorsal and ventral regions showed MEG–fMRI correspondence in representations later than early visual cortex. Together, these results provide a novel and comprehensive, spatio-temporally resolved view of the rapid neural dynamics during the first few hundred milliseconds of object vision. They further demonstrate the feasibility of spatially unbiased representational similarity-based fusion of MEG and fMRI, promising new insights into how the brain computes complex cognitive functions. PMID:27235099

Mapping the spatio-temporal structure of motor cortical LFP and spiking activities during reach-to-grasp movements

PubMed Central

Riehle, Alexa; Wirtssohn, Sarah; Grün, Sonja; Brochier, Thomas

2013-01-01

Grasping an object involves shaping the hand and fingers in relation to the object’s physical properties. Following object contact, it also requires a fine adjustment of grasp forces for secure manipulation. Earlier studies suggest that the control of hand shaping and grasp force involve partially segregated motor cortical networks. However, it is still unclear how information originating from these networks is processed and integrated. We addressed this issue by analyzing massively parallel signals from population measures (local field potentials, LFPs) and single neuron spiking activities recorded simultaneously during a delayed reach-to-grasp task, by using a 100-electrode array chronically implanted in monkey motor cortex. Motor cortical LFPs exhibit a large multi-component movement-related potential (MRP) around movement onset. Here, we show that the peak amplitude of each MRP component and its latency with respect to movement onset vary along the cortical surface covered by the array. Using a comparative mapping approach, we suggest that the spatio-temporal structure of the MRP reflects the complex physical properties of the reach-to-grasp movement. In addition, we explored how the spatio-temporal structure of the MRP relates to two other measures of neuronal activity: the temporal profile of single neuron spiking activity at each electrode site and the somatosensory receptive field properties of single neuron activities. We observe that the spatial representations of LFP and spiking activities overlap extensively and relate to the spatial distribution of proximal and distal representations of the upper limb. Altogether, these data show that, in motor cortex, a precise spatio-temporal pattern of activation is involved for the control of reach-to-grasp movements and provide some new insight about the functional organization of motor cortex during reaching and object manipulation. PMID:23543888

The RNA-Editing Enzyme ADAR1 Controls Innate Immune Responses to RNA

PubMed Central

Mannion, Niamh M.; Greenwood, Sam M.; Young, Robert; Cox, Sarah; Brindle, James; Read, David; Nellåker, Christoffer; Vesely, Cornelia; Ponting, Chris P.; McLaughlin, Paul J.; Jantsch, Michael F.; Dorin, Julia; Adams, Ian R.; Scadden, A.D.J.; Öhman, Marie; Keegan, Liam P.; O’Connell, Mary A.

2014-01-01

Summary The ADAR RNA-editing enzymes deaminate adenosine bases to inosines in cellular RNAs. Aberrant interferon expression occurs in patients in whom ADAR1 mutations cause Aicardi-Goutières syndrome (AGS) or dystonia arising from striatal neurodegeneration. Adar1 mutant mouse embryos show aberrant interferon induction and die by embryonic day E12.5. We demonstrate that Adar1 embryonic lethality is rescued to live birth in Adar1; Mavs double mutants in which the antiviral interferon induction response to cytoplasmic double-stranded RNA (dsRNA) is prevented. Aberrant immune responses in Adar1 mutant mouse embryo fibroblasts are dramatically reduced by restoring the expression of editing-active cytoplasmic ADARs. We propose that inosine in cellular RNA inhibits antiviral inflammatory and interferon responses by altering RLR interactions. Transfecting dsRNA oligonucleotides containing inosine-uracil base pairs into Adar1 mutant mouse embryo fibroblasts reduces the aberrant innate immune response. ADAR1 mutations causing AGS affect the activity of the interferon-inducible cytoplasmic isoform more severely than the nuclear isoform. PMID:25456137

The RNA-editing enzyme ADAR1 controls innate immune responses to RNA.

PubMed

Mannion, Niamh M; Greenwood, Sam M; Young, Robert; Cox, Sarah; Brindle, James; Read, David; Nellåker, Christoffer; Vesely, Cornelia; Ponting, Chris P; McLaughlin, Paul J; Jantsch, Michael F; Dorin, Julia; Adams, Ian R; Scadden, A D J; Ohman, Marie; Keegan, Liam P; O'Connell, Mary A

2014-11-20

The ADAR RNA-editing enzymes deaminate adenosine bases to inosines in cellular RNAs. Aberrant interferon expression occurs in patients in whom ADAR1 mutations cause Aicardi-Goutières syndrome (AGS) or dystonia arising from striatal neurodegeneration. Adar1 mutant mouse embryos show aberrant interferon induction and die by embryonic day E12.5. We demonstrate that Adar1 embryonic lethality is rescued to live birth in Adar1; Mavs double mutants in which the antiviral interferon induction response to cytoplasmic double-stranded RNA (dsRNA) is prevented. Aberrant immune responses in Adar1 mutant mouse embryo fibroblasts are dramatically reduced by restoring the expression of editing-active cytoplasmic ADARs. We propose that inosine in cellular RNA inhibits antiviral inflammatory and interferon responses by altering RLR interactions. Transfecting dsRNA oligonucleotides containing inosine-uracil base pairs into Adar1 mutant mouse embryo fibroblasts reduces the aberrant innate immune response. ADAR1 mutations causing AGS affect the activity of the interferon-inducible cytoplasmic isoform more severely than the nuclear isoform. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Monolithic hybrid optics for focusing ultrashort laser pulses

NASA Astrophysics Data System (ADS)

Fuchs, U.

2014-03-01

Almost any application of ultrashort laser pulses involves focusing them in order to reach high intensities and/or small spot sizes as needed for micro-machining or Femto-LASIK. Hence, it is indispensable to be able to understand pulse front distortion caused by real world optics. Focusing causes pulse front distortion due to aberrations, dispersion and diffraction. Thus, the spatio-temporal profile of ultrashort laser is altered, which increases automatically the pulse duration and the focusing spot. Consequently, the main advantage of having ultrashort laser pulses - pulse durations way below 100 fs - can be lost in that one last step of the experimental set-up by focusing them unfavorable. Since compensating for dispersion, aberration and diffraction effects is quite complicated and not always possible, we pursue a different approach. We present a specially designed monolithic hybrid optics comprising refraction and diffraction effects for tight spatial and temporal focusing of ultrashort laser pulses. Both aims can be put into practice by having a high numerical aperture (NA = 0.35) and low internal dispersion at the same time. The focusing properties are very promising, due to a design, which provides diffraction limited focusing for 100 nm bandwidth at 780 nm center wavelength. Thus, pulses with durations as short as 10 fs can be focused without pulse front distortion. The outstanding performance of this optics is shown in theory and experimentally. Above that, such focusing optics are easily adapted to their special purpose - changing the center wavelength, achromatic bandwidth or even correcting for focusing into material is possible.

Cigarette smoke induces aberrant EGF receptor activation which mediates lung cancer development and resistance to tyrosine kinase inhibitors

PubMed Central

Filosto, Simone; Becker, Cathleen R.; Goldkorn, Tzipora

2015-01-01

The EGF Receptor (EGFR) and its downstream signaling are implicated in lung cancer development. Therefore, much effort was spent in developing specific tyrosine kinase inhibitors (TKIs) that bind to the EGFR ATP-pocket, blocking EGFR phosphorylation/signaling. Clinical use of TKIs is effective in a subset of lung cancers with mutations in the EGFR kinase domain, rendering the receptor highly susceptible to TKIs. However, these benefits are limited, and emergence of additional EGFR mutations usually results in TKI resistance and disease progression. Previously, we demonstrated one mechanism linking cigarette smoke (CS) to EGFR-driven lung cancer. Specifically, exposure of lung epithelial cells to CS-induced oxidative stress stimulates aberrant EGFR phosphorylation/activation with impaired receptor ubiquitination/degradation. The abnormal stabilization of the activated receptor leads to uncontrolled cell growth and tumorigenesis. Here we describe for the first time a novel post-translational mechanism of EGFR resistance to TKIs. Exposure of airway epithelial cells to CS causes aberrant phosphorylation/activation of EGFR, resulting in a conformation that is different from that induced by the ligand EGF. Unlike EGF-activated EGFR, CS-activated EGFR binds c-Src and caveolin-1 and does not undergo canonical dimerization. Importantly, the CS-activated EGFR is not inhibited by TKIs (AG1478; Erlotinib; Gefitinib); in fact, the CS exposure induces TKI-resistance even in the TKI-sensitive EGFR mutants. Our findings demonstrate that CS exposure stimulates not only aberrant EGFR phosphorylation impairing receptor degradation, but also induces a different EGFR conformation and signaling that are resistant to TKIs. Together, these findings offer new insights into CS-induced lung cancer development and TKI resistance. PMID:22302097

Spatio-Temporal Patterning in Primary Motor Cortex at Movement Onset.

PubMed

Best, Matthew D; Suminski, Aaron J; Takahashi, Kazutaka; Brown, Kevin A; Hatsopoulos, Nicholas G

2017-02-01

Voluntary movement initiation involves the engagement of large populations of motor cortical neurons around movement onset. Despite knowledge of the temporal dynamics that lead to movement, the spatial structure of these dynamics across the cortical surface remains unknown. In data from 4 rhesus macaques, we show that the timing of attenuation of beta frequency local field potential oscillations, a correlate of locally activated cortex, forms a spatial gradient across primary motor cortex (MI). We show that these spatio-temporal dynamics are recapitulated in the engagement order of ensembles of MI neurons. We demonstrate that these patterns are unique to movement onset and suggest that movement initiation requires a precise spatio-temporal sequential activation of neurons in MI. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Atypical Functional Brain Activation during a Multiple Object Tracking Task in Girls with Turner Syndrome: Neurocorrelates of Reduced Spatiotemporal Resolution

ERIC Educational Resources Information Center

Beaton, Elliott A.; Stoddard, Joel; Lai, Song; Lackey, John; Shi, Jianrong; Ross, Judith L.; Simon, Tony J.

2010-01-01

Turner syndrome is associated with spatial and numerical cognitive impairments. We hypothesized that these nonverbal cognitive impairments result from limits in spatial and temporal processing, particularly as it affects attention. To examine spatiotemporal attention in girls with Turner syndrome versus typically developing controls, we used a…

[The polymorphism of catechol-O-methyltransferase (COMT) and hemochromatosis (HFE) genes in the radiocontaminated regions residents with different chromosome aberration frequency].

PubMed

Ivanova, T I; Kondrashova, T V; Krikunova, L I; Smirnova, I A; Shentereva, N I; Sychenkova, N I; Rykova, E V; Zharikova, I A; Khorokhorina, V A; Riabchenko, N I; Zamulaeva, I A

2010-01-01

The association between polymorphisms in genes COMT, HFE that takes part in oxidative stress regulation, and chromosome aberration frequency in lymphocytes was assessed in 278 female residents of radiation polluted regions of Central Russia: Bryansk (322 kBk/m2) and Tula Districts (137Cs - 171 kBk/m2). The C187G, G845A genotyping of HFE and G1947A (H/L) of COMT was done by means of polymerase chain reaction-restriction fragment length polymorphism. Studied population was divided into 3 subgroups by level of chromosome aberrations per cell (0-2, 3-4, >5). There was shown statistically significant difference in distribution of COMTand HFE genotypes between the groups. The high frequency of chromosome aberrations (> or = 5%) was associated with homozygotes of the high activity COMT G/G and HFE CC. Heterozygotes for G1947A COMT and C187G HFE reveal negative association with the high frequency of chromosome aberrations and correspond to "resistance factors".

Two types of putative preneoplastic lesions identified by hexosaminidase activity in whole-mounts of colons from F344 rats treated with carcinogen.

PubMed

Pretlow, T P; O'Riordan, M A; Spancake, K M; Pretlow, T G

1993-06-01

Previous studies identified as putative preneoplastic lesions 1) enzyme-altered foci in sections of methacrylate-embedded colon and 2) aberrant crypts in methylene blue-stained unembedded (whole-mount) colon and established that aberrant crypts embedded in methacrylate had enzyme alterations. We have now studied histochemically demonstrable hexosaminidase activity in unembedded or whole-mount preparations of colons from carcinogen-treated rats. These preparations have revealed two populations of crypts that are enzyme-altered: those that are morphologically altered or aberrant and those that are morphologically normal. Both populations can be quantified rigorously in less than an hour with whole-mount preparations reacted for hexosaminidase. The demonstration of phenotypic characteristics with histochemical techniques in whole-mount preparations should have wide applicability to functional studies in many normal and diseased tissues.

The MLH1 ATPase domain is needed for suppressing aberrant formation of interstitial telomeric sequences.

PubMed

Jia, Pingping; Chai, Weihang

2018-05-01

Genome instability gives rise to cancer. MLH1, commonly known for its important role in mismatch repair (MMR), DNA damage signaling and double-strand break (DSB) repair, safeguards genome stability. Recently we have reported a novel role of MLH1 in preventing aberrant formation of interstitial telomeric sequences (ITSs) at intra-chromosomal regions. Deficiency in MLH1, in particular its N-terminus, leads to an increase of ITSs. Here, we identify that the ATPase activity in the MLH1 N-terminal domain is important for suppressing the formation of ITSs. The ATPase activity is also needed for recruiting MLH1 to DSBs. Moreover, defective ATPase activity of MLH1 causes an increase in micronuclei formation. Our results highlight the crucial role of MLH1's ATPase domain in preventing the aberrant formation of telomeric sequences at the intra-chromosomal regions and preserving genome stability. Copyright © 2018 Elsevier B.V. All rights reserved.

Balance of corneal horizontal coma by internal optics in eyes with intraocular artificial lenses: evidence of a passive mechanism.

PubMed

Marcos, Susana; Rosales, Patricia; Llorente, Lourdes; Barbero, Sergio; Jiménez-Alfaro, I

2008-01-01

It is well known that the aberrations of the cornea are partially compensated by the aberrations of the internal optics of the eye (primarily the crystalline lens) in young subjects. This effect has been found not only for the spherical aberration, but also for horizontal coma. It has been debated whether the compensation of horizontal coma is the result of passive mechanism [Artal, P., Benito, A., & Tabernero, J. (2006). The human eye is an example of robust optical design. Journal of Vision, 6 (1), 1-7] or through an active developmental feedback process [Kelly, J. E., Mihashi, T., & Howland, H. C. (2004). Compensation of corneal horizontal/vertical astigmatism, lateral coma, and spherical aberration by internal optics of the eye. Journal of Vision, 4 (4), 262-271]. In this study we investigate the active or passive nature of the horizontal coma compensation using eyes with artificial lenses, where no active developmental process can be present. We measured total and corneal aberrations, and lens tilt and decentration in a group of 38 eyes implanted with two types of intraocular lenses designed to compensate the corneal spherical aberration of the average population. We found that spherical aberration was compensated by 66%, and horizontal coma by 87% on average. The spherical aberration is not compensated at an individual level, but horizontal coma is compensated individually (coefficients of correlation corneal/internal aberration: -0.946, p<0.0001). The fact that corneal (but not total) horizontal coma is highly correlated with angle lamda (computed from the shift of the 1st Purkinje image from the pupil center, for foveal fixation) indicates that the compensation arises primarily from the geometrical configuration of the eye (which generates horizontal coma of opposite signs in the cornea and internal optics). The amount and direction of tilts and misalignments of the lens are comparable to those found in young eyes, and on average tend to compensate (rather than increase) horizontal coma. Computer simulations using customized model eyes and different designs of intraocular lenses show that, while not all designs produce a compensation of horizontal coma, a wide range of aspheric biconvex designs may produce comparable compensation to that found in young eyes with crystalline lenses, over a relatively large field of view. These findings suggest that the lens shape, gradient index or foveal location do not need to be fine-tuned to achieve a compensation of horizontal coma. Our results cannot exclude a fine-tuning for the orientation of the crystalline lens, since cataract surgery seems to preserve the position of the capsule.

Dynamic decomposition of spatiotemporal neural signals

PubMed Central

2017-01-01

Neural signals are characterized by rich temporal and spatiotemporal dynamics that reflect the organization of cortical networks. Theoretical research has shown how neural networks can operate at different dynamic ranges that correspond to specific types of information processing. Here we present a data analysis framework that uses a linearized model of these dynamic states in order to decompose the measured neural signal into a series of components that capture both rhythmic and non-rhythmic neural activity. The method is based on stochastic differential equations and Gaussian process regression. Through computer simulations and analysis of magnetoencephalographic data, we demonstrate the efficacy of the method in identifying meaningful modulations of oscillatory signals corrupted by structured temporal and spatiotemporal noise. These results suggest that the method is particularly suitable for the analysis and interpretation of complex temporal and spatiotemporal neural signals. PMID:28558039

Clinimetric properties of the Tinetti Mobility Test, Four Square Step Test, Activities-specific Balance Confidence Scale, and spatiotemporal gait measures in individuals with Huntington's disease

PubMed Central

Kloos, Anne D.; Fritz, Nora E.; Kostyk, Sandra K.; Young, Gregory S.; Kegelmeyer, Deb A.

2014-01-01

Background and purpose Individuals with Huntington's disease (HD) experience balance and gait problems that lead to falls. Clinicians currently have very little information about the reliability and validity of outcome measures to determine the efficacy of interventions that aim to reduce balance and gait impairments in HD. This study examined the reliability and concurrent validity of spatiotemporal gait measures, the Tinetti Mobility Test (TMT), Four Square Step Test (FSST), and Activities-specific Balance Confidence (ABC) Scale in individuals with HD. Methods Participants with HD [n = 20; mean age ± SD = 50.9 ± 13.7; 7 male] were tested on spatiotemporal gait measures the TMT, FSST, and ABC Scale before and after a six week period to determine test–retest reliability and minimal detectable change (MDC) values. Linear relationships between gait and clinical measures were estimated using Pearson's correlation coefficients. Results Spatiotemporal gait measures, the TMT total and the FSST showed good to excellent test–retest reliability (ICC > 0.75). MDC values were 0.30 m/s and 0.17 m/s for velocity in forward and backward walking respectively, four points for the TMT, and 3 s for the FSST. The TMT and FSST were highly correlated with most spatiotemporal measures. The ABC Scale demonstrated lower reliability and less concurrent validity than other measures. Conclusions The high test–retest reliability over a six week period and concurrent validity between the TMT, FSST, and spatiotemporal gait measures suggest that the TMT and FSST may be useful outcome measures for future intervention studies in ambulatory individuals with HD. PMID:25128156

Clinimetric properties of the Tinetti Mobility Test, Four Square Step Test, Activities-specific Balance Confidence Scale, and spatiotemporal gait measures in individuals with Huntington's disease.

PubMed

Kloos, Anne D; Fritz, Nora E; Kostyk, Sandra K; Young, Gregory S; Kegelmeyer, Deb A

2014-09-01

Individuals with Huntington's disease (HD) experience balance and gait problems that lead to falls. Clinicians currently have very little information about the reliability and validity of outcome measures to determine the efficacy of interventions that aim to reduce balance and gait impairments in HD. This study examined the reliability and concurrent validity of spatiotemporal gait measures, the Tinetti Mobility Test (TMT), Four Square Step Test (FSST), and Activities-specific Balance Confidence (ABC) Scale in individuals with HD. Participants with HD [n = 20; mean age ± SD=50.9 ± 13.7; 7 male] were tested on spatiotemporal gait measures and the TMT, FSST, and ABC Scale before and after a six week period to determine test-retest reliability and minimal detectable change (MDC) values. Linear relationships between gait and clinical measures were estimated using Pearson's correlation coefficients. Spatiotemporal gait measures, the TMT total and the FSST showed good to excellent test-retest reliability (ICC > 0.75). MDC values were 0.30 m/s and 0.17 m/s for velocity in forward and backward walking respectively, four points for the TMT, and 3s for the FSST. The TMT and FSST were highly correlated with most spatiotemporal measures. The ABC Scale demonstrated lower reliability and less concurrent validity than other measures. The high test-retest reliability over a six week period and concurrent validity between the TMT, FSST, and spatiotemporal gait measures suggest that the TMT and FSST may be useful outcome measures for future intervention studies in ambulatory individuals with HD. Copyright © 2014 Elsevier B.V. All rights reserved.

Aberrant Axonal Arborization of PDF Neurons Induced by Aβ42-Mediated JNK Activation Underlies Sleep Disturbance in an Alzheimer's Model.

PubMed

Song, Qian; Feng, Ge; Huang, Zehua; Chen, Xiaoman; Chen, Zhaohuan; Ping, Yong

2017-10-01

Impaired sleep patterns are common symptoms of Alzheimer's disease (AD). Cellular mechanisms underlying sleep disturbance in AD remain largely unknown. Here, using a Drosophila Aβ42 AD model, we show that Aβ42 markedly decreases sleep in a large population, which is accompanied with postdevelopmental axonal arborization of wake-promoting pigment-dispersing factor (PDF) neurons. The arborization is mediated in part via JNK activation and can be reversed by decreasing JNK signaling activity. Axonal arborization and impaired sleep are correlated in Aβ42 and JNK kinase hemipterous mutant flies. Image reconstruction revealed that these aberrant fibers preferentially project to pars intercerebralis (PI), a fly brain region analogous to the mammalian hypothalamus. Moreover, PDF signaling in PI neurons was found to modulate sleep/wake activities, suggesting that excessive release of PDF by these aberrant fibers may lead to the impaired sleep in Aβ42 flies. Finally, inhibition of JNK activation in Aβ42 flies restores nighttime sleep loss, decreases Aβ42 accumulation, and attenuates neurodegeneration. These data provide a new mechanism by which sleep disturbance could be induced by Aβ42 burden, a key initiator of a complex pathogenic cascade in AD.

Artificial spatiotemporal touch inputs reveal complementary decoding in neocortical neurons.

PubMed

Oddo, Calogero M; Mazzoni, Alberto; Spanne, Anton; Enander, Jonas M D; Mogensen, Hannes; Bengtsson, Fredrik; Camboni, Domenico; Micera, Silvestro; Jörntell, Henrik

2017-04-04

Investigations of the mechanisms of touch perception and decoding has been hampered by difficulties in achieving invariant patterns of skin sensor activation. To obtain reproducible spatiotemporal patterns of activation of sensory afferents, we used an artificial fingertip equipped with an array of neuromorphic sensors. The artificial fingertip was used to transduce real-world haptic stimuli into spatiotemporal patterns of spikes. These spike patterns were delivered to the skin afferents of the second digit of rats via an array of stimulation electrodes. Combined with low-noise intra- and extracellular recordings from neocortical neurons in vivo, this approach provided a previously inaccessible high resolution analysis of the representation of tactile information in the neocortical neuronal circuitry. The results indicate high information content in individual neurons and reveal multiple novel neuronal tactile coding features such as heterogeneous and complementary spatiotemporal input selectivity also between neighboring neurons. Such neuronal heterogeneity and complementariness can potentially support a very high decoding capacity in a limited population of neurons. Our results also indicate a potential neuroprosthetic approach to communicate with the brain at a very high resolution and provide a potential novel solution for evaluating the degree or state of neurological disease in animal models.

Artificial spatiotemporal touch inputs reveal complementary decoding in neocortical neurons

PubMed Central

Oddo, Calogero M.; Mazzoni, Alberto; Spanne, Anton; Enander, Jonas M. D.; Mogensen, Hannes; Bengtsson, Fredrik; Camboni, Domenico; Micera, Silvestro; Jörntell, Henrik

2017-01-01

Investigations of the mechanisms of touch perception and decoding has been hampered by difficulties in achieving invariant patterns of skin sensor activation. To obtain reproducible spatiotemporal patterns of activation of sensory afferents, we used an artificial fingertip equipped with an array of neuromorphic sensors. The artificial fingertip was used to transduce real-world haptic stimuli into spatiotemporal patterns of spikes. These spike patterns were delivered to the skin afferents of the second digit of rats via an array of stimulation electrodes. Combined with low-noise intra- and extracellular recordings from neocortical neurons in vivo, this approach provided a previously inaccessible high resolution analysis of the representation of tactile information in the neocortical neuronal circuitry. The results indicate high information content in individual neurons and reveal multiple novel neuronal tactile coding features such as heterogeneous and complementary spatiotemporal input selectivity also between neighboring neurons. Such neuronal heterogeneity and complementariness can potentially support a very high decoding capacity in a limited population of neurons. Our results also indicate a potential neuroprosthetic approach to communicate with the brain at a very high resolution and provide a potential novel solution for evaluating the degree or state of neurological disease in animal models. PMID:28374841

Spatiotemporal relations of primary sensorimotor and secondary motor activation patterns mapped by NIR imaging

PubMed Central

Khan, Bilal; Chand, Pankaj; Alexandrakis, George

2011-01-01

Functional near infrared (fNIR) imaging was used to identify spatiotemporal relations between spatially distinct cortical regions activated during various hand and arm motion protocols. Imaging was performed over a field of view (FOV, 12 x 8.4 cm) including the secondary motor, primary sensorimotor, and the posterior parietal cortices over a single brain hemisphere. This is a more extended FOV than typically used in current fNIR studies. Three subjects performed four motor tasks that induced activation over this extended FOV. The tasks included card flipping (pronation and supination) that, to our knowledge, has not been performed in previous functional magnetic resonance imaging (fMRI) or fNIR studies. An earlier rise and a longer duration of the hemodynamic activation response were found in tasks requiring increased physical or mental effort. Additionally, analysis of activation images by cluster component analysis (CCA) demonstrated that cortical regions can be grouped into clusters, which can be adjacent or distant from each other, that have similar temporal activation patterns depending on whether the performed motor task is guided by visual or tactile feedback. These analyses highlight the future potential of fNIR imaging to tackle clinically relevant questions regarding the spatiotemporal relations between different sensorimotor cortex regions, e.g. ones involved in the rehabilitation response to motor impairments. PMID:22162826

Spatiotemporal dynamics of word retrieval in speech production revealed by cortical high-frequency band activity.

PubMed

Riès, Stephanie K; Dhillon, Rummit K; Clarke, Alex; King-Stephens, David; Laxer, Kenneth D; Weber, Peter B; Kuperman, Rachel A; Auguste, Kurtis I; Brunner, Peter; Schalk, Gerwin; Lin, Jack J; Parvizi, Josef; Crone, Nathan E; Dronkers, Nina F; Knight, Robert T

2017-06-06

Word retrieval is core to language production and relies on complementary processes: the rapid activation of lexical and conceptual representations and word selection, which chooses the correct word among semantically related competitors. Lexical and conceptual activation is measured by semantic priming. In contrast, word selection is indexed by semantic interference and is hampered in semantically homogeneous (HOM) contexts. We examined the spatiotemporal dynamics of these complementary processes in a picture naming task with blocks of semantically heterogeneous (HET) or HOM stimuli. We used electrocorticography data obtained from frontal and temporal cortices, permitting detailed spatiotemporal analysis of word retrieval processes. A semantic interference effect was observed with naming latencies longer in HOM versus HET blocks. Cortical response strength as indexed by high-frequency band (HFB) activity (70-150 Hz) amplitude revealed effects linked to lexical-semantic activation and word selection observed in widespread regions of the cortical mantle. Depending on the subsecond timing and cortical region, HFB indexed semantic interference (i.e., more activity in HOM than HET blocks) or semantic priming effects (i.e., more activity in HET than HOM blocks). These effects overlapped in time and space in the left posterior inferior temporal gyrus and the left prefrontal cortex. The data do not support a modular view of word retrieval in speech production but rather support substantial overlap of lexical-semantic activation and word selection mechanisms in the brain.

Granulocytes' enzymes as biomarkers of radiotoxicity in individuals occupationally exposed to low-level radiation.

PubMed

Milacic, S

2009-01-01

To investigate the possibility of using the granulocytes' enzymes alkaline phosphatase (L-ALP) and myeloperoxidase (MPO) as biomarkers to study and analyse contamination of nuclear medicine personnel working with radionuclides (RN) when radiotoxic effects are very low, before occupational radiation illness or benign haematological disorders and malignant diseases have occurred. Also, to investigate the relationship between chromosomal aberrations in lymphocytes and the activity of L-ALP and MPO in neutrophil granulocytes (NphG). The absorbed external doses of ionizing radiation (IR) were measured by thermoluminescent personal dosimeters (TLD) for the duration of occupational exposure (DOE). Urine radioactivity was measured by gamma- spectrometry. Venous blood was used for leukocyte count and search for chromosomal aberrations by conventional cytogenetic techniques. Blood smears were stained for L-ALP and MPO using a modified Kaplow's method and the classical method with benzidine dihydrochloride, respectively. The occupationally exposed group (E) consisted of 74 workers exposed to short-life radioactive isotopes I131 (beta and mostly gamma emission) and mTc99 (gamma emission). The control group (C) consisted of 52 subjects living in the same region, working in the same institution, occupationally not exposed to RN. A patients' group (P; n=31) took I131 or mTc99 for diagnostic purposes. Although the measured values did not exceed the yearly quota for professionally exposed individuals, characteristic chromosomal aberrations in peripheral blood lymphocytes (dicentrics, fragments, rings) were identified. L-ALP and MPO activity was inhibited in the NphG in occupationally exposed workers, especially in persons with chromosomal aberrations, working for a long time in ionizing radiations zones (p <0.01). Decreased activity of L-ALP and MPO can reveal effects of long-lasting exposure to low-dose IR. A significant relationship between chromosomal aberrations in lymphocytes and activity of the enzymes in granulocytes was found.

Two types of putative preneoplastic lesions identified by hexosaminidase activity in whole-mounts of colons from F344 rats treated with carcinogen.

PubMed Central

Pretlow, T. P.; O'Riordan, M. A.; Spancake, K. M.; Pretlow, T. G.

1993-01-01

Previous studies identified as putative preneoplastic lesions 1) enzyme-altered foci in sections of methacrylate-embedded colon and 2) aberrant crypts in methylene blue-stained unembedded (whole-mount) colon and established that aberrant crypts embedded in methacrylate had enzyme alterations. We have now studied histochemically demonstrable hexosaminidase activity in unembedded or whole-mount preparations of colons from carcinogen-treated rats. These preparations have revealed two populations of crypts that are enzyme-altered: those that are morphologically altered or aberrant and those that are morphologically normal. Both populations can be quantified rigorously in less than an hour with whole-mount preparations reacted for hexosaminidase. The demonstration of phenotypic characteristics with histochemical techniques in whole-mount preparations should have wide applicability to functional studies in many normal and diseased tissues. Images Figure 1 PMID:8506941

Modulation of V1 Spike Response by Temporal Interval of Spatiotemporal Stimulus Sequence

PubMed Central

Kim, Taekjun; Kim, HyungGoo R.; Kim, Kayeon; Lee, Choongkil

2012-01-01

The spike activity of single neurons of the primary visual cortex (V1) becomes more selective and reliable in response to wide-field natural scenes compared to smaller stimuli confined to the classical receptive field (RF). However, it is largely unknown what aspects of natural scenes increase the selectivity of V1 neurons. One hypothesis is that modulation by surround interaction is highly sensitive to small changes in spatiotemporal aspects of RF surround. Such a fine-tuned modulation would enable single neurons to hold information about spatiotemporal sequences of oriented stimuli, which extends the role of V1 neurons as a simple spatiotemporal filter confined to the RF. In the current study, we examined the hypothesis in the V1 of awake behaving monkeys, by testing whether the spike response of single V1 neurons is modulated by temporal interval of spatiotemporal stimulus sequence encompassing inside and outside the RF. We used two identical Gabor stimuli that were sequentially presented with a variable stimulus onset asynchrony (SOA): the preceding one (S1) outside the RF and the following one (S2) in the RF. This stimulus configuration enabled us to examine the spatiotemporal selectivity of response modulation from a focal surround region. Although S1 alone did not evoke spike responses, visual response to S2 was modulated for SOA in the range of tens of milliseconds. These results suggest that V1 neurons participate in processing spatiotemporal sequences of oriented stimuli extending outside the RF. PMID:23091631

Spatio-Temporal Brain Mapping of Motion-Onset VEPs Combined with fMRI and Retinotopic Maps

PubMed Central

Pitzalis, Sabrina; Strappini, Francesca; De Gasperis, Marco; Bultrini, Alessandro; Di Russo, Francesco

2012-01-01

Neuroimaging studies have identified several motion-sensitive visual areas in the human brain, but the time course of their activation cannot be measured with these techniques. In the present study, we combined electrophysiological and neuroimaging methods (including retinotopic brain mapping) to determine the spatio-temporal profile of motion-onset visual evoked potentials for slow and fast motion stimuli and to localize its neural generators. We found that cortical activity initiates in the primary visual area (V1) for slow stimuli, peaking 100 ms after the onset of motion. Subsequently, activity in the mid-temporal motion-sensitive areas, MT+, peaked at 120 ms, followed by peaks in activity in the more dorsal area, V3A, at 160 ms and the lateral occipital complex at 180 ms. Approximately 250 ms after stimulus onset, activity fast motion stimuli was predominant in area V6 along the parieto-occipital sulcus. Finally, at 350 ms (100 ms after the motion offset) brain activity was visible again in area V1. For fast motion stimuli, the spatio-temporal brain pattern was similar, except that the first activity was detected at 70 ms in area MT+. Comparing functional magnetic resonance data for slow vs. fast motion, we found signs of slow-fast motion stimulus topography along the posterior brain in at least three cortical regions (MT+, V3A and LOR). PMID:22558222

CLASSICAL AREAS OF PHENOMENOLOGY: Correcting dynamic residual aberrations of conformal optical systems using AO technology

NASA Astrophysics Data System (ADS)

Li, Yan; Li, Lin; Huang, Yi-Fan; Du, Bao-Lin

2009-07-01

This paper analyses the dynamic residual aberrations of a conformal optical system and introduces adaptive optics (AO) correction technology to this system. The image sharpening AO system is chosen as the correction scheme. Communication between MATLAB and Code V is established via ActiveX technique in computer simulation. The SPGD algorithm is operated at seven zoom positions to calculate the optimized surface shape of the deformable mirror. After comparison of performance of the corrected system with the baseline system, AO technology is proved to be a good way of correcting the dynamic residual aberration in conformal optical design.

Enhanced neuronal expression of major histocompatibility complex class I leads to aberrations in neurodevelopment and neurorepair

PubMed Central

Wu, Zhongqi-Phyllis; Washburn, Lorraine; Bilousova, Tina V.; Boudzinskaia, Maia; Escande-Beillard, Nathalie; Querubin, Jyes; Dang, Hoa; Xie, Cui-Wei; Tian, Jide; Kaufman, Daniel L.

2012-01-01

Mice deficient in classical major histocompatibility complex class I (MHCI) have aberrations in neurodevelopment. The consequences of up-regulated neuronal MHCI expression have not been examined. We found that transgenic C57Bl/6 mice that are engineered to express higher levels of self-Db on their CNS neurons have alterations in their hippocampal morphology and retinogeniculate projections, as well as impaired neurorepair responses. Thus, enhanced neuronal classical MHCI expression can lead to aberrations in neural circuitry and neurorepair. These findings complement a growing body of knowledge concerning the neurobiological activities of MHCI and may have potential clinical relevance. PMID:20950866

Human cytomegalovirus UL76 induces chromosome aberrations

PubMed Central

2009-01-01

Background Human cytomegalovirus (HCMV) is known to induce chromosome aberrations in infected cells, which can lead to congenital abnormalities in infected fetuses. HCMV UL76 belongs to a conserved protein family from herpesviruses. Some reported roles among UL76 family members include involvement in virulence determination, lytic replication, reactivation of latent virus, modulation of gene expression, induction of apoptosis, and perturbation of cell cycle progression, as well as potential nuclease activity. Previously, we have shown that stable expression of UL76 inhibits HCMV replication in glioblastoma cells. Methods To examine chromosomal integrity and the DNA damage signal γ-H2AX in cells constitutively expressing UL76, immunofluorescent cell staining and Western blotting were performed. The comet assay was employed to assess DNA breaks in cells transiently expressing UL76. Results We report that stably transfected cells expressing UL76 developed chromosome aberrations including micronuclei and misaligned chromosomes, lagging and bridging. In mitotic cells expressing UL76, aberrant spindles were increased compared to control cells. However, cells with supernumerary centrosomes were marginally increased in UL76-expressing cells relative to control cells. We further demonstrated that UL76-expressing cells activated the DNA damage signal γ-H2AX and caused foci formation in nuclei. In addition, the number of cells with DNA breaks increased in proportion to UL76 protein levels. Conclusion Our findings suggest that the virus-associated protein UL76 induces DNA damage and the accumulation of chromosome aberrations. PMID:19930723

Aberration influence and active compensation on laser mode properties for asymmetric folded resonators

NASA Astrophysics Data System (ADS)

Zhang, Xiang; Hu, Zhiqiu; Yang, Wentao; Su, Likun

2017-09-01

We demonstrate the influence on mode features with introducing typical intracavity perturbation and results of aberrated wavefront compensation in a folded-type unstable resonator used in high energy lasers. The mode properties and aberration coefficient with intracavity misalignment are achieved by iterative calculation and Zernike polynomial fitting. Experimental results for the relation of intracavity maladjustment and mode characteristics are further obtained in terms of S-H detection and model wavefront reconstruction. It indicates that intracavity phase perturbation has significant influence on out coupling beam properties, and the uniform and symmetry of the mode is rapidly disrupted even by a slight misalignment of the resonator mirrors. Meanwhile, the far-field beam patterns will obviously degrade with increasing the distance between the convex mirror and the phase perturbation position even if the equivalent disturbation is inputted into such the resonator. The closed-loop device for compensating intracavity low order aberration is successfully fabricated. Moreover, Zernike defocus aberration is also effectively controlled by precisely adjusting resonator length, and the beam quality is noticeably improved.

A genetically encoded fluorescent sensor of ERK activity.

PubMed

Harvey, Christopher D; Ehrhardt, Anka G; Cellurale, Cristina; Zhong, Haining; Yasuda, Ryohei; Davis, Roger J; Svoboda, Karel

2008-12-09

The activity of the ERK has complex spatial and temporal dynamics that are important for the specificity of downstream effects. However, current biochemical techniques do not allow for the measurement of ERK signaling with fine spatiotemporal resolution. We developed a genetically encoded, FRET-based sensor of ERK activity (the extracellular signal-regulated kinase activity reporter, EKAR), optimized for signal-to-noise ratio and fluorescence lifetime imaging. EKAR selectively and reversibly reported ERK activation in HEK293 cells after epidermal growth factor stimulation. EKAR signals were correlated with ERK phosphorylation, required ERK activity, and did not report the activities of JNK or p38. EKAR reported ERK activation in the dendrites and nucleus of hippocampal pyramidal neurons in brain slices after theta-burst stimuli or trains of back-propagating action potentials. EKAR therefore permits the measurement of spatiotemporal ERK signaling dynamics in living cells, including in neuronal compartments in intact tissues.

Active Correction of Aperture Discontinuities-Optimized Stroke Minimization. I. A New Adaptive Interaction Matrix Algorithm

NASA Astrophysics Data System (ADS)

Mazoyer, J.; Pueyo, L.; N'Diaye, M.; Fogarty, K.; Zimmerman, N.; Leboulleux, L.; St. Laurent, K. E.; Soummer, R.; Shaklan, S.; Norman, C.

2018-01-01

Future searches for bio-markers on habitable exoplanets will rely on telescope instruments that achieve extremely high contrast at small planet-to-star angular separations. Coronagraphy is a promising starlight suppression technique, providing excellent contrast and throughput for off-axis sources on clear apertures. However, the complexity of space- and ground-based telescope apertures goes on increasing over time, owing to the combination of primary mirror segmentation, the secondary mirror, and its support structures. These discontinuities in the telescope aperture limit the coronagraph performance. In this paper, we present ACAD-OSM, a novel active method to correct for the diffractive effects of aperture discontinuities in the final image plane of a coronagraph. Active methods use one or several deformable mirrors that are controlled with an interaction matrix to correct for the aberrations in the pupil. However, they are often limited by the amount of aberrations introduced by aperture discontinuities. This algorithm relies on the recalibration of the interaction matrix during the correction process to overcome this limitation. We first describe the ACAD-OSM technique and compare it to the previous active methods for the correction of aperture discontinuities. We then show its performance in terms of contrast and off-axis throughput for static aperture discontinuities (segmentation, struts) and for some aberrations evolving over the life of the instrument (residual phase aberrations, artifacts in the aperture, misalignments in the coronagraph design). This technique can now obtain the Earth-like planet detection threshold of {10}10 contrast on any given aperture over at least a 10% spectral bandwidth, with several coronagraph designs.

Microenvironmental cooperation promotes early spread and bistability of a Warburg-like phenotype.

PubMed

Fernandez-de-Cossio-Diaz, Jorge; De Martino, Andrea; Mulet, Roberto

2017-06-08

We introduce an in silico model for the initial spread of an aberrant phenotype with Warburg-like overflow metabolism within a healthy homeostatic tissue in contact with a nutrient reservoir (the blood), aimed at characterizing the role of the microenvironment for aberrant growth. Accounting for cellular metabolic activity, competition for nutrients, spatial diffusion and their feedbacks on aberrant replication and death rates, we obtain a phase portrait where distinct asymptotic whole-tissue states are found upon varying the tissue-blood turnover rate and the level of blood-borne primary nutrient. Over a broad range of parameters, the spreading dynamics is bistable as random fluctuations can impact the final state of the tissue. Such a behaviour turns out to be linked to the re-cycling of overflow products by non-aberrant cells. Quantitative insight on the overall emerging picture is provided by a spatially homogeneous version of the model.

PDGF-BB Promotes Type I IFN-Dependent Vascular Alterations and Monocyte Recruitment in a Model of Dermal Fibrosis.

PubMed

Cho, John S; Fang, Terry C; Reynolds, Taylor L; Sofia, Daniel J; Hamann, Stefan; Burkly, Linda C

2016-01-01

Systemic sclerosis (SSc) is a chronic autoimmune disorder that can result in extensive tissue damage in the skin and, in advanced cases, internal organs. Vasculopathy, aberrant immune activation, and tissue fibrosis are three hallmarks of the disease that have been identified, with vasculopathy and aberrant immunity being amongst the earliest events. However, a mechanistic link between these processes has not been established. Here, we have identified a novel role of platelet derived growth factor-BB (PDGF-BB)/PDGFRβ activation in combination with dermal injury induced by bleomycin as a driver of early, aberrant expression of interferon stimulatory genes (ISGs) and inflammatory monocyte infiltration. Activation of PDGFRβ in combination with bleomycin-induced dermal injury resulted in increased dermal thickness, vascular density, monocyte/macrophage infiltration, and exacerbation of tissue injury. Many of these features were dependent on IFNAR-signaling, and an increase in the number of interferon-beta (IFN-β) producing monocytes cells was found in the skin lesions. Taken together, these results identify a novel link between PDGFRβ activation, and Type I IFN-driven vascular maintenance and monocyte/macrophage cell recruitment, and provide a potential explanation linking key features of SSc that were previously thought to be unrelated.

NOTCH1 Is Aberrantly Activated in Chronic Lymphocytic Leukemia Hematopoietic Stem Cells.

PubMed

Di Ianni, Mauro; Baldoni, Stefano; Del Papa, Beatrice; Aureli, Patrizia; Dorillo, Erica; De Falco, Filomena; Albi, Elisa; Varasano, Emanuela; Di Tommaso, Ambra; Giancola, Raffaella; Accorsi, Patrizia; Rotta, Gianluca; Rompietti, Chiara; Silva Barcelos, Estevão Carlos; Campese, Antonio Francesco; Di Bartolomeo, Paolo; Screpanti, Isabella; Rosati, Emanuela; Falzetti, Franca; Sportoletti, Paolo

2018-01-01

To investigate chronic lymphocytic leukemia (CLL)-initiating cells, we assessed NOTCH1 mutation/expression in hematopoietic stem cells (HSCs). In NOTCH1- mutated CLL, we detected subclonal mutations in 57% CD34+/CD38- HSCs. NOTCH1 mutation was present in 66% CD34+/CD38+ progenitor cells displaying an increased mutational burden compared to HSCs. Flow cytometric analysis revealed significantly higher NOTCH1 activation in CD34+/CD38- and CD34+/CD38+ cells from CLL patients, regardless NOTCH1 mutation compared to healthy donors. Activated NOTCH1 resulted in overexpression of the NOTCH1 target c-MYC. We conclude that activated NOTCH1 is an early event in CLL that may contribute to aberrant HSCs in this disease.

Exclusive destruction of mitotic spindles in human cancer cells.

PubMed

Visochek, Leonid; Castiel, Asher; Mittelman, Leonid; Elkin, Michael; Atias, Dikla; Golan, Talia; Izraeli, Shai; Peretz, Tamar; Cohen-Armon, Malka

2017-03-28

We identified target proteins modified by phenanthrenes that cause exclusive eradication of human cancer cells. The cytotoxic activity of the phenanthrenes in a variety of human cancer cells is attributed by these findings to post translational modifications of NuMA and kinesins HSET/kifC1 and kif18A. Their activity prevented the binding of NuMA to α-tubulin and kinesins in human cancer cells, and caused aberrant spindles. The most efficient cytotoxic activity of the phenanthridine PJ34, caused significantly smaller aberrant spindles with disrupted spindle poles and scattered extra-centrosomes and chromosomes. Concomitantly, PJ34 induced tumor growth arrest of human malignant tumors developed in athymic nude mice, indicating the relevance of its activity for cancer therapy.

A Riboproteomic Platform to Identify Novel Targets for Prostate Cancer Therapy

DTIC Science & Technology

2015-10-01

cell lines derived from RWPE1 prostatic epithelial cells after exposure to N-methyl-N- nitrosourea (MNU) (these cell lines are commercially available...is well established that the malignancy of cells is strongly linked to and dependent on aberrant protein synthesis . Current knowledge clearly...highlights deregulation of protein synthesis , in the development of prostate cancer, through aberrant activation of classical signaling pathways. It has

Histone Deacetylase Inhibitors Repress Tumoral Expression of the Proinvasive Factor RUNX2.

PubMed

Sancisi, Valentina; Gandolfi, Greta; Ambrosetti, Davide Carlo; Ciarrocchi, Alessia

2015-05-01

Aberrant reactivation of embryonic pathways occurs commonly in cancer. The transcription factor RUNX2 plays a fundamental role during embryogenesis and is aberrantly reactivated during progression and metastasization of different types of human tumors. In this study, we attempted to dissect the molecular mechanisms governing RUNX2 expression and its aberrant reactivation. We identified a new regulatory enhancer element, located within the RUNX2 gene, which is responsible for the activation of the RUNX2 promoter and for the regulation of its expression in cancer cells. Furthermore, we have shown that treatment with the anticancer compounds histone deacetylase inhibitor (HDACi) results in a profound inhibition of RUNX2 expression, which is determined by the disruption of the transcription-activating complex on the identified enhancer. These data envisage a possible targeting strategy to counteract the oncongenic function of RUNX2 in cancer cells and provide evidence that the cytotoxic activity of HDACi in cancer is not only dependent on the reactivation of silenced oncosuppressors but also on the repression of oncogenic factors that are necessary for survival and progression. ©2015 American Association for Cancer Research.

Chronic Stress Alters Striosome-Circuit Dynamics, Leading to Aberrant Decision-Making.

PubMed

Friedman, Alexander; Homma, Daigo; Bloem, Bernard; Gibb, Leif G; Amemori, Ken-Ichi; Hu, Dan; Delcasso, Sebastien; Truong, Timothy F; Yang, Joyce; Hood, Adam S; Mikofalvy, Katrina A; Beck, Dirk W; Nguyen, Norah; Nelson, Erik D; Toro Arana, Sebastian E; Vorder Bruegge, Ruth H; Goosens, Ki A; Graybiel, Ann M

2017-11-16

Effective evaluation of costs and benefits is a core survival capacity that in humans is considered as optimal, "rational" decision-making. This capacity is vulnerable in neuropsychiatric disorders and in the aftermath of chronic stress, in which aberrant choices and high-risk behaviors occur. We report that chronic stress exposure in rodents produces abnormal evaluation of costs and benefits resembling non-optimal decision-making in which choices of high-cost/high-reward options are sharply increased. Concomitantly, alterations in the task-related spike activity of medial prefrontal neurons correspond with increased activity of their striosome-predominant striatal projection neuron targets and with decreased and delayed striatal fast-firing interneuron activity. These effects of chronic stress on prefronto-striatal circuit dynamics could be blocked or be mimicked by selective optogenetic manipulation of these circuits. We suggest that altered excitation-inhibition dynamics of striosome-based circuit function could be an underlying mechanism by which chronic stress contributes to disorders characterized by aberrant decision-making under conflict. VIDEO ABSTRACT. Copyright © 2017 Elsevier Inc. All rights reserved.

Disentangling multidimensional spatio-temporal data into their common and aberrant responses

DOE PAGES

Chang, Young Hwan; Korkola, James; Amin, Dhara N.; ...

2015-04-22

With the advent of high-throughput measurement techniques, scientists and engineers are starting to grapple with massive data sets and encountering challenges with how to organize, process and extract information into meaningful structures. Multidimensional spatio-temporal biological data sets such as time series gene expression with various perturbations over different cell lines, or neural spike trains across many experimental trials, have the potential to acquire insight about the dynamic behavior of the system. For this potential to be realized, we need a suitable representation to understand the data. A general question is how to organize the observed data into meaningful structures andmore » how to find an appropriate similarity measure. A natural way of viewing these complex high dimensional data sets is to examine and analyze the large-scale features and then to focus on the interesting details. Since the wide range of experiments and unknown complexity of the underlying system contribute to the heterogeneity of biological data, we develop a new method by proposing an extension of Robust Principal Component Analysis (RPCA), which models common variations across multiple experiments as the lowrank component and anomalies across these experiments as the sparse component. We show that the proposed method is able to find distinct subtypes and classify data sets in a robust way without any prior knowledge by separating these common responses and abnormal responses. Thus, the proposed method provides us a new representation of these data sets which has the potential to help users acquire new insight from data.« less

Dynamic Reorganization of Functional Connectivity Reveals Abnormal Temporal Efficiency in Schizophrenia.

PubMed

Sun, Yu; Collinson, Simon L; Suckling, John; Sim, Kang

2018-06-07

Emerging evidence suggests that schizophrenia is associated with brain dysconnectivity. Nonetheless, the implicit assumption of stationary functional connectivity (FC) adopted in most previous resting-state functional magnetic resonance imaging (fMRI) studies raises an open question of schizophrenia-related aberrations in dynamic properties of resting-state FC. This study introduces an empirical method to examine the dynamic functional dysconnectivity in patients with schizophrenia. Temporal brain networks were estimated from resting-state fMRI of 2 independent datasets (patients/controls = 18/19 and 53/57 for self-recorded dataset and a publicly available replication dataset, respectively) by the correlation of sliding time-windowed time courses among regions of a predefined atlas. Through the newly introduced temporal efficiency approach and temporal random network models, we examined, for the first time, the 3D spatiotemporal architecture of the temporal brain network. We found that although prominent temporal small-world properties were revealed in both groups, temporal brain networks of patients with schizophrenia in both datasets showed a significantly higher temporal global efficiency, which cannot be simply attributable to head motion and sampling error. Specifically, we found localized changes of temporal nodal properties in the left frontal, right medial parietal, and subcortical areas that were associated with clinical features of schizophrenia. Our findings demonstrate that altered dynamic FC may underlie abnormal brain function and clinical symptoms observed in schizophrenia. Moreover, we provide new evidence to extend the dysconnectivity hypothesis in schizophrenia from static to dynamic brain network and highlight the potential of aberrant brain dynamic FC in unraveling the pathophysiologic mechanisms of the disease.

Altered local spontaneous activity in frontal lobe epilepsy: a resting-state functional magnetic resonance imaging study.

PubMed

Dong, Li; Li, Hechun; He, Zhongqiong; Jiang, Sisi; Klugah-Brown, Benjamin; Chen, Lin; Wang, Pu; Tan, Song; Luo, Cheng; Yao, Dezhong

2016-11-01

The purpose of this study was to investigate the local spatiotemporal consistency of spontaneous brain activity in patients with frontal lobe epilepsy (FLE). Eyes closed resting-state functional magnetic resonance imaging (fMRI) data were collected from 19 FLE patients and 19 age- and gender-matched healthy controls. A novel measure, named FOur-dimensional (spatiotemporal) Consistency of local neural Activities (FOCA) was used to assess the spatiotemporal consistency of local spontaneous activity (emphasizing both local temporal homogeneity and regional stability of brain activity states). Then, two-sample t test was performed to detect the FOCA differences between two groups. Partial correlations between the FOCA values and durations of epilepsy were further analyzed. Compared with controls, FLE patients demonstrated increased FOCA in distant brain regions including the frontal and parietal cortices, as well as the basal ganglia. The decreased FOCA was located in the temporal cortex, posterior default model regions, and cerebellum. In addition, the FOCA measure was linked to the duration of epilepsy in basal ganglia. Our study suggested that alterations of local spontaneous activity in frontoparietal cortex and basal ganglia was associated with the pathophysiology of FLE; and the abnormality in frontal and default model regions might account for the potential cognitive impairment in FLE. We also presumed that the FOCA measure had potential to provide important insights into understanding epilepsy such as FLE.

Spatiotemporal Patterns of Noise-Driven Confined Actin Waves in Living Cells.

PubMed

Bernitt, Erik; Döbereiner, Hans-Günther

2017-01-27

Cells utilize waves of polymerizing actin to reshape their morphologies, which is central to physiological and pathological processes alike. Here, we force dorsal actin waves to propagate on one-dimensional domains with periodic boundary conditions, which results in striking spatiotemporal patterns with a clear signature of noise-driven dynamics. We show that these patterns can be very closely reproduced with a noise-driven active medium at coherence resonance.

The zebrafish eye—a paradigm for investigating human ocular genetics

PubMed Central

Richardson, R; Tracey-White, D; Webster, A; Moosajee, M

2017-01-01

Although human epidemiological and genetic studies are essential to elucidate the aetiology of normal and aberrant ocular development, animal models have provided us with an understanding of the pathogenesis of multiple developmental ocular malformations. Zebrafish eye development displays in depth molecular complexity and stringent spatiotemporal regulation that incorporates developmental contributions of the surface ectoderm, neuroectoderm and head mesenchyme, similar to that seen in humans. For this reason, and due to its genetic tractability, external fertilisation, and early optical clarity, the zebrafish has become an invaluable vertebrate system to investigate human ocular development and disease. Recently, zebrafish have been at the leading edge of preclinical therapy development, with their amenability to genetic manipulation facilitating the generation of robust ocular disease models required for large-scale genetic and drug screening programmes. This review presents an overview of human and zebrafish ocular development, genetic methodologies employed for zebrafish mutagenesis, relevant models of ocular disease, and finally therapeutic approaches, which may have translational leads in the future. PMID:27612182

Structural and numerical chromosome aberration inducers in liver micronucleus test in rats with partial hepatectomy.

PubMed

Itoh, Satoru; Hattori, Chiharu; Nagata, Mayumi; Sanbuissho, Atsushi

2012-08-30

The liver micronucleus test is an important method to detect pro-mutagens such as active metabolites not reaching bone marrow due to their short lifespan. We have already reported that dosing of the test compound after partial hepatectomy (PH) is essential to detect genotoxicity of numerical chromosome aberration inducers in mice [Mutat. Res. 632 (2007) 89-98]. In naive animals, the proportion of binucleated cells in rats is less than half of that in mice, which suggests a species difference in the response to chromosome aberration inducers. In the present study, we investigated the responses to structural and numerical chromosome aberration inducers in the rat liver micronucleus test. Two structural chromosome aberretion inducers (diethylnitrosamine and 1,2-dimethylhydrazine) and two numerical chromosome aberration inducers (colchicine and carbendazim) were used in the present study. PH was performed a day before or after the dosing of the test compound in 8-week old male F344 rats and hepatocytes were isolated 4 days after the PH. As a result, diethylnitrosamine and 1,2-dimethylhydrazine, structural chromosome aberration inducers, exhibited significant increase in the incidence of micronucleated hepatocyte (MNH) when given either before and after PH. Colchicine and carbendazim, numerical chromosome aberration inducers, did not result in any toxicologically significant increase in MNH frequency when given before PH, while they exhibited MNH induction when given after PH. It is confirmed that dosing after PH is essential in order to detect genotoxicity of numerical chromosome aberration inducers in rats as well as in mice. Regarding the species difference, a different temporal response to colchicine was identified. Colchicine increased the incidence of MNH 4 days after PH in rats, although such induction in mice was observed 8-10 days after PH. Copyright © 2012 Elsevier B.V. All rights reserved.

Spatiotemporal dynamics of word retrieval in speech production revealed by cortical high-frequency band activity

PubMed Central

Dhillon, Rummit K.; Clarke, Alex; King-Stephens, David; Laxer, Kenneth D.; Weber, Peter B.; Kuperman, Rachel A.; Auguste, Kurtis I.; Brunner, Peter; Lin, Jack J.; Parvizi, Josef; Crone, Nathan E.; Dronkers, Nina F.; Knight, Robert T.

2017-01-01

Word retrieval is core to language production and relies on complementary processes: the rapid activation of lexical and conceptual representations and word selection, which chooses the correct word among semantically related competitors. Lexical and conceptual activation is measured by semantic priming. In contrast, word selection is indexed by semantic interference and is hampered in semantically homogeneous (HOM) contexts. We examined the spatiotemporal dynamics of these complementary processes in a picture naming task with blocks of semantically heterogeneous (HET) or HOM stimuli. We used electrocorticography data obtained from frontal and temporal cortices, permitting detailed spatiotemporal analysis of word retrieval processes. A semantic interference effect was observed with naming latencies longer in HOM versus HET blocks. Cortical response strength as indexed by high-frequency band (HFB) activity (70–150 Hz) amplitude revealed effects linked to lexical-semantic activation and word selection observed in widespread regions of the cortical mantle. Depending on the subsecond timing and cortical region, HFB indexed semantic interference (i.e., more activity in HOM than HET blocks) or semantic priming effects (i.e., more activity in HET than HOM blocks). These effects overlapped in time and space in the left posterior inferior temporal gyrus and the left prefrontal cortex. The data do not support a modular view of word retrieval in speech production but rather support substantial overlap of lexical-semantic activation and word selection mechanisms in the brain. PMID:28533406

Optogenetically induced spatiotemporal gamma oscillations and neuronal spiking activity in primate motor cortex.

PubMed

Lu, Yao; Truccolo, Wilson; Wagner, Fabien B; Vargas-Irwin, Carlos E; Ozden, Ilker; Zimmermann, Jonas B; May, Travis; Agha, Naubahar S; Wang, Jing; Nurmikko, Arto V

2015-06-01

Transient gamma-band (40-80 Hz) spatiotemporal patterns are hypothesized to play important roles in cortical function. Here we report the direct observation of gamma oscillations as spatiotemporal waves induced by targeted optogenetic stimulation, recorded by intracortical multichannel extracellular techniques in macaque monkeys during their awake resting states. Microelectrode arrays integrating an optical fiber at their center were chronically implanted in primary motor (M1) and ventral premotor (PMv) cortices of two subjects. Targeted brain tissue was transduced with the red-shifted opsin C1V1(T/T). Constant (1-s square pulses) and ramp stimulation induced narrowband gamma oscillations during awake resting states. Recordings across 95 microelectrodes (4 × 4-mm array) enabled us to track the transient gamma spatiotemporal patterns manifested, e.g., as concentric expanding and spiral waves. Gamma oscillations were induced well beyond the light stimulation volume, via network interactions at distal electrode sites, depending on optical power. Despite stimulation-related modulation in spiking rates, neuronal spiking remained highly asynchronous during induced gamma oscillations. In one subject we examined stimulation effects during preparation and execution of a motor task and observed that movement execution largely attenuated optically induced gamma oscillations. Our findings demonstrate that, beyond previously reported induced gamma activity under periodic drive, a prolonged constant stimulus above a certain threshold may carry primate motor cortex network dynamics into gamma oscillations, likely via a Hopf bifurcation. More broadly, the experimental capability in combining microelectrode array recordings and optogenetic stimulation provides an important approach for probing spatiotemporal dynamics in primate cortical networks during various physiological and behavioral conditions.

Optogenetically induced spatiotemporal gamma oscillations and neuronal spiking activity in primate motor cortex

PubMed Central

Lu, Yao; Truccolo, Wilson; Wagner, Fabien B.; Vargas-Irwin, Carlos E.; Ozden, Ilker; Zimmermann, Jonas B.; May, Travis; Agha, Naubahar S.; Wang, Jing

2015-01-01

Transient gamma-band (40–80 Hz) spatiotemporal patterns are hypothesized to play important roles in cortical function. Here we report the direct observation of gamma oscillations as spatiotemporal waves induced by targeted optogenetic stimulation, recorded by intracortical multichannel extracellular techniques in macaque monkeys during their awake resting states. Microelectrode arrays integrating an optical fiber at their center were chronically implanted in primary motor (M1) and ventral premotor (PMv) cortices of two subjects. Targeted brain tissue was transduced with the red-shifted opsin C1V1(T/T). Constant (1-s square pulses) and ramp stimulation induced narrowband gamma oscillations during awake resting states. Recordings across 95 microelectrodes (4 × 4-mm array) enabled us to track the transient gamma spatiotemporal patterns manifested, e.g., as concentric expanding and spiral waves. Gamma oscillations were induced well beyond the light stimulation volume, via network interactions at distal electrode sites, depending on optical power. Despite stimulation-related modulation in spiking rates, neuronal spiking remained highly asynchronous during induced gamma oscillations. In one subject we examined stimulation effects during preparation and execution of a motor task and observed that movement execution largely attenuated optically induced gamma oscillations. Our findings demonstrate that, beyond previously reported induced gamma activity under periodic drive, a prolonged constant stimulus above a certain threshold may carry primate motor cortex network dynamics into gamma oscillations, likely via a Hopf bifurcation. More broadly, the experimental capability in combining microelectrode array recordings and optogenetic stimulation provides an important approach for probing spatiotemporal dynamics in primate cortical networks during various physiological and behavioral conditions. PMID:25761956

The research of conformal optical design

NASA Astrophysics Data System (ADS)

Li, Lin; Li, Yan; Huang, Yi-fan; Du, Bao-lin

2009-07-01

Conformal optical domes are characterized as having external more elongated optical surfaces that are optimized to minimize drag, increased missile velocity and extended operational range. The outer surface of the conformal domes typically deviate greatly from spherical surface descriptions, so the inherent asymmetry of conformal surfaces leads to variations in the aberration content presented to the optical sensor as it is gimbaled across the field of regard, which degrades the sensor's ability to properly image targets of interest and then undermine the overall system performance. Consequently, the aerodynamic advantages of conformal domes cannot be realized in practical systems unless the dynamic aberration correction techniques are developed to restore adequate optical imaging capabilities. Up to now, many optical correction solutions have been researched in conformal optical design, including static aberrations corrections and dynamic aberrations corrections. There are three parts in this paper. Firstly, the combination of static and dynamic aberration correction is introduced. A system for correcting optical aberration created by a conformal dome has an outer surface and an inner surface. The optimization of the inner surface is regard as the static aberration correction; moreover, a deformable mirror is placed at the position of the secondary mirror in the two-mirror all reflective imaging system, which is the dynamic aberration correction. Secondly, the using of appropriate surface types is very important in conformal dome design. Better performing optical systems can result from surface types with adequate degrees of freedom to describe the proper corrector shape. Two surface types and the methods of using them are described, including Zernike polynomial surfaces used in correct elements and user-defined surfaces used in deformable mirror (DM). Finally, the Adaptive optics (AO) correction is presented. In order to correct the dynamical residual aberration in conformal optical design, the SPGD optimization algorithm is operated at each zoom position to calculate the optimized surface shape of the MEMS DM. The communication between MATLAB and Code V established via ActiveX technique is applied in simulation analysis.

Spatiotemporal Processing in Crossmodal Interactions for Perception of the External World: A Review

PubMed Central

Hidaka, Souta; Teramoto, Wataru; Sugita, Yoichi

2015-01-01

Research regarding crossmodal interactions has garnered much interest in the last few decades. A variety of studies have demonstrated that multisensory information (vision, audition, tactile sensation, and so on) can perceptually interact with each other in the spatial and temporal domains. Findings regarding crossmodal interactions in the spatiotemporal domain (i.e., motion processing) have also been reported, with updates in the last few years. In this review, we summarize past and recent findings on spatiotemporal processing in crossmodal interactions regarding perception of the external world. A traditional view regarding crossmodal interactions holds that vision is superior to audition in spatial processing, but audition is dominant over vision in temporal processing. Similarly, vision is considered to have dominant effects over the other sensory modalities (i.e., visual capture) in spatiotemporal processing. However, recent findings demonstrate that sound could have a driving effect on visual motion perception. Moreover, studies regarding perceptual associative learning reported that, after association is established between a sound sequence without spatial information and visual motion information, the sound sequence could trigger visual motion perception. Other sensory information, such as motor action or smell, has also exhibited similar driving effects on visual motion perception. Additionally, recent brain imaging studies demonstrate that similar activation patterns could be observed in several brain areas, including the motion processing areas, between spatiotemporal information from different sensory modalities. Based on these findings, we suggest that multimodal information could mutually interact in spatiotemporal processing in the percept of the external world and that common perceptual and neural underlying mechanisms would exist for spatiotemporal processing. PMID:26733827

How to Link Brain and Experience? Spatiotemporal Psychopathology of the Lived Body

PubMed Central

Northoff, Georg; Stanghellini, Giovanni

2016-01-01

The focus of the present article is on sketching a psychopathology of the body in schizophrenia and linking it to brain activity. This is done providing converging data from psychopathological evidence (phenomenal), phenomenological contructs (trans-phenomenal) and neuroscientific measures (pre-phenomenal). The phenomenal level is the detailed documentation of the patients’ subjective anomalous experiences. These phenomena are explicit contents in the patients’ field of consciousness. The trans-phenomenal level targets the implicit yet operative matrix that underlies these anomalous subjective experiences. Abnormal phenomena are viewed as expressions of a modification of trans-phenomenal matrix, that is, in terms of an abnormal synthesis or integration through time of intero-, proprio- and extero-ceptive stimuli. Finally, we link the abnormalities of the trans-phenomenal matrix to pre-phenomenal alterations of the brain resting state and of its spatio-temporal organization, as documented by neurobiological methods providing spatial and temporal resolution of intrinsic brain activity (with many features of the resting state remaining yet unclear though). Based on phenomenological research, the body in schizophrenia is typically experienced in an itemized way as an object external to one’s self and unrelated to events in the external world. Based on neurobiological data, we tentatively hypothesize that such anomalies of the lived body are related to decreased integration between intero-, extero- and proprioceptive experiences by the brain’s spontaneous activity and its temporal structure. Taken all together, this suggests that we view abnormalities of bodily experience in terms of their underlying abnormal spatiotemporal features which, as we suppose, can be traced back to the spatiotemporal features of the brain’s spontaneous activity. PMID:27199695

An electromyographic study on the sequential recruitment of bilateral sternocleidomastoid and masseter muscle activity during gum chewing.

PubMed

Guo, S-X; Li, B-Y; Zhang, Y; Zhou, L-J; Liu, L; Widmalm, S-E; Wang, M-Q

2017-08-01

Mandibular functions are associated with electromyographic activity of the jaw muscles and also the sternocleidomastoid muscle (SCM). The precise spatiotemporal relation of SCM and masticatory muscles activities during chewing is worthy of investigation. To analyse the sequential recruitment of SCM and masseter activities during chewing as indicated by the spatiotemporal locations of their activity peaks. Jaw movements and bilateral surface electromyographic activity of SCM and masseter were recorded during gum chewing in 20 healthy subjects. The timing order was decided by comparing the length of time from the time when the opening started to the time when the surface electromyographic activity reached its peak value. Spatial order was analysed by locating the peak electromyographic activity onto a standard chewing cycle which was created based on 15 unilateral chewing cycles. Paired t-test, one-way ANOVA and Student-Newman-Keuls post-test were used for comparisons. Although the Time to Peak for the balancing side SCM appeared shorter than for the other three tested muscles, most often it did not reach a level of significance. However, the location of the balancing side SCM's peak activity was further from the terminal chewing position (TCP) than the working side SCM and bilateral masseters (P < 0·05). The balancing side SCM activity reached its peak significantly further away from TCP than the other three tested muscles during chewing. Further studies with spatiotemporal variables included should be helpful to understand the roles of the head, neck and jaw muscles in orofacial and cervical dysfunctional problems. © 2017 John Wiley & Sons Ltd.

Increasing Endocannabinoid Levels in the Ventral Pallidum Restore Aberrant Dopamine Neuron Activity in the Subchronic PCP Rodent Model of Schizophrenia

PubMed Central

Chen, Li; Lodge, Daniel J

2015-01-01

Background: Schizophrenia is a debilitating disorder that affects 1% of the US population. While the exogenous administration of cannabinoids such as tetrahydrocannabinol is reported to exacerbate psychosis in schizophrenia patients, augmenting the levels of endogenous cannabinoids has gained attention as a possible alternative therapy to schizophrenia due to clinical and preclinical observations. Thus, patients with schizophrenia demonstrate an inverse relationship between psychotic symptoms and levels of the endocannabinoid anandamide. In addition, increasing endocannabinoid levels (by blockade of enzymatic degradation) has been reported to attenuate social withdrawal in a preclinical model of schizophrenia. Here we examine the effects of increasing endogenous cannabinoids on dopamine neuron activity in the sub-chronic phencyclidine (PCP) model. Aberrant dopamine system function is thought to underlie the positive symptoms of schizophrenia. Methods: Using in vivo extracellular recordings in chloral hydrate–anesthetized rats, we now demonstrate an increase in dopamine neuron population activity in PCP-treated rats. Results: Interestingly, endocannabinoid upregulation, induced by URB-597, was able to normalize this aberrant dopamine neuron activity. Furthermore, we provide evidence that the ventral pallidum is the site where URB-597 acts to restore ventral tegmental area activity. Conclusions: Taken together, we provide preclinical evidence that augmenting endogenous cannabinoids may be an effective therapy for schizophrenia, acting in part to restore ventral pallidal activity. PMID:25539511

Mapping child maltreatment risk: a 12-year spatio-temporal analysis of neighborhood influences.

PubMed

Gracia, Enrique; López-Quílez, Antonio; Marco, Miriam; Lila, Marisol

2017-10-18

'Place' matters in understanding prevalence variations and inequalities in child maltreatment risk. However, most studies examining ecological variations in child maltreatment risk fail to take into account the implications of the spatial and temporal dimensions of neighborhoods. In this study, we conduct a high-resolution small-area study to analyze the influence of neighborhood characteristics on the spatio-temporal epidemiology of child maltreatment risk. We conducted a 12-year (2004-2015) small-area Bayesian spatio-temporal epidemiological study with all families with child maltreatment protection measures in the city of Valencia, Spain. As neighborhood units, we used 552 census block groups. Cases were geocoded using the family address. Neighborhood-level characteristics analyzed included three indicators of neighborhood disadvantage-neighborhood economic status, neighborhood education level, and levels of policing activity-, immigrant concentration, and residential instability. Bayesian spatio-temporal modelling and disease mapping methods were used to provide area-specific risk estimations. Results from a spatio-temporal autoregressive model showed that neighborhoods with low levels of economic and educational status, with high levels of policing activity, and high immigrant concentration had higher levels of substantiated child maltreatment risk. Disease mapping methods were used to analyze areas of excess risk. Results showed chronic spatial patterns of high child maltreatment risk during the years analyzed, as well as stability over time in areas of low risk. Areas with increased or decreased child maltreatment risk over the years were also observed. A spatio-temporal epidemiological approach to study the geographical patterns, trends over time, and the contextual determinants of child maltreatment risk can provide a useful method to inform policy and action. This method can offer a more accurate description of the problem, and help to inform more localized prevention and intervention strategies. This new approach can also contribute to an improved epidemiological surveillance system to detect ecological variations in risk, and to assess the effectiveness of the initiatives to reduce this risk.

Oscillatory neural network for pattern recognition: trajectory based classification and supervised learning.

PubMed

Miller, Vonda H; Jansen, Ben H

2008-12-01

Computer algorithms that match human performance in recognizing written text or spoken conversation remain elusive. The reasons why the human brain far exceeds any existing recognition scheme to date in the ability to generalize and to extract invariant characteristics relevant to category matching are not clear. However, it has been postulated that the dynamic distribution of brain activity (spatiotemporal activation patterns) is the mechanism by which stimuli are encoded and matched to categories. This research focuses on supervised learning using a trajectory based distance metric for category discrimination in an oscillatory neural network model. Classification is accomplished using a trajectory based distance metric. Since the distance metric is differentiable, a supervised learning algorithm based on gradient descent is demonstrated. Classification of spatiotemporal frequency transitions and their relation to a priori assessed categories is shown along with the improved classification results after supervised training. The results indicate that this spatiotemporal representation of stimuli and the associated distance metric is useful for simple pattern recognition tasks and that supervised learning improves classification results.

Spatiotemporal neuromodulation therapies engaging muscle synergies improve motor control after spinal cord injury

PubMed Central

Wenger, Nikolaus; Moraud, Eduardo Martin; Gandar, Jerome; Musienko, Pavel; Capogrosso, Marco; Baud, Laetitia; Le Goff, Camille G.; Barraud, Quentin; Pavlova, Natalia; Dominici, Nadia; Minev, Ivan R.; Asboth, Leonie; Hirsch, Arthur; Duis, Simone; Kreider, Julie; Mortera, Andrea; Haverbeck, Oliver; Kraus, Silvio; Schmitz, Felix; DiGiovanna, Jack; van den Brand, Rubia; Bloch, Jocelyne; Detemple, Peter; Lacour, Stéphanie P.; Bézard, Erwan; Micera, Silvestro; Courtine, Grégoire

2016-01-01

Electrical neuromodulation of lumbar segments improves motor control after spinal cord injury in animal models and humans. However, the physiological principles underlying the effect of this intervention remain poorly understood, which has limited this therapeutic approach to continuous stimulation applied to restricted spinal cord locations. Here, we developed novel stimulation protocols that reproduce the natural dynamics of motoneuron activation during locomotion. For this, we computed the spatiotemporal activation pattern of muscle synergies during locomotion in healthy rats. Computer simulations identified optimal electrode locations to target each synergy through the recruitment of proprioceptive feedback circuits. This framework steered the design of spatially selective spinal implants and real–time control software that modulate extensor versus flexor synergies with precise temporal resolution. Spatiotemporal neuromodulation therapies improved gait quality, weight–bearing capacities, endurance and skilled locomotion in multiple rodent models of spinal cord injury. These new concepts are directly translatable to strategies to improve motor control in humans. PMID:26779815

Spatiotemporal control of opioid signaling and behavior

PubMed Central

Siuda, Edward R.; Copits, Bryan A.; Schmidt, Martin J.; Baird, Madison A.; Al-Hasani, Ream; Planer, William J.; Funderburk, Samuel C.; McCall, Jordan G.; Gereau, Robert W.; Bruchas, Michael R.

2015-01-01

Summary Optogenetics is now a widely accepted tool for spatiotemporal manipulation of neuronal activity. However, a majority of optogenetic approaches use binary on/off control schemes. Here we extend the optogenetic toolset by developing a neuromodulatory approach using a rationale-based design to generate a Gi-coupled, optically-sensitive, mu-opioid-like receptor, we term opto-MOR. We demonstrate that opto-MOR engages canonical mu-opioid signaling through inhibition of adenylyl cyclase, activation of MAPK and G protein-gated inward rectifying potassium (GIRK) channels, and internalizes with similar kinetics as the mu-opioid receptor. To assess in vivo utility we expressed a Cre-dependent viral opto-MOR in RMTg/VTA GABAergic neurons, which led to a real-time place preference. In contrast, expression of opto-MOR in GABAergic neurons of the ventral pallidum hedonic cold spot, led to real-time place aversion. This tool has generalizable application for spatiotemporal control of opioid signaling and, furthermore, can be used broadly for mimicking endogenous neuronal inhibition pathways. PMID:25937173

Design, Fabrication, and Validation of an Ultra-Lightweight Membrane Mirror (Conference Proceedings)

DTIC Science & Technology

2005-08-01

Membrane Mirror Active boundary control is very promising and studies predict good control over astigmatism and coma aberrations. However, the primary...design analysis. The mount has a split lenticular setup, allowing one canopy and many membrane mirrors that can be interchanged. The mount has a...spherical aberration, which is as expected. Results from finite element modeling showed that astigmatism can be corrected with the normal actuators

Spatiotemporal differentiation in auditory and motor regions during auditory phoneme discrimination.

PubMed

Aerts, Annelies; Strobbe, Gregor; van Mierlo, Pieter; Hartsuiker, Robert J; Corthals, Paul; Santens, Patrick; De Letter, Miet

2017-06-01

Auditory phoneme discrimination (APD) is supported by both auditory and motor regions through a sensorimotor interface embedded in a fronto-temporo-parietal cortical network. However, the specific spatiotemporal organization of this network during APD with respect to different types of phonemic contrasts is still unclear. Here, we use source reconstruction, applied to event-related potentials in a group of 47 participants, to uncover a potential spatiotemporal differentiation in these brain regions during a passive and active APD task with respect to place of articulation (PoA), voicing and manner of articulation (MoA). Results demonstrate that in an early stage (50-110 ms), auditory, motor and sensorimotor regions elicit more activation during the passive and active APD task with MoA and active APD task with voicing compared to PoA. In a later stage (130-175 ms), the same auditory and motor regions elicit more activation during the APD task with PoA compared to MoA and voicing, yet only in the active condition, implying important timing differences. Degree of attention influences a frontal network during the APD task with PoA, whereas auditory regions are more affected during the APD task with MoA and voicing. Based on these findings, it can be carefully suggested that APD is supported by the integration of early activation of auditory-acoustic properties in superior temporal regions, more perpetuated for MoA and voicing, and later auditory-to-motor integration in sensorimotor areas, more perpetuated for PoA.

Male veterans with PTSD exhibit aberrant neural dynamics during working memory processing: an MEG study

PubMed Central

McDermott, Timothy J.; Badura-Brack, Amy S.; Becker, Katherine M.; Ryan, Tara J.; Khanna, Maya M.; Heinrichs-Graham, Elizabeth; Wilson, Tony W.

2016-01-01

Background Posttraumatic stress disorder (PTSD) is associated with executive functioning deficits, including disruptions in working memory. In this study, we examined the neural dynamics of working memory processing in veterans with PTSD and a matched healthy control sample using magnetoencephalography (MEG). Methods Our sample of recent combat veterans with PTSD and demographically matched participants without PTSD completed a working memory task during a 306-sensor MEG recording. The MEG data were preprocessed and transformed into the time-frequency domain. Significant oscillatory brain responses were imaged using a beamforming approach to identify spatiotemporal dynamics. Results Fifty-one men were included in our analyses: 27 combat veterans with PTSD and 24 controls. Across all participants, a dynamic wave of neural activity spread from posterior visual cortices to left frontotemporal regions during encoding, consistent with a verbal working memory task, and was sustained throughout maintenance. Differences related to PTSD emerged during early encoding, with patients exhibiting stronger α oscillatory responses than controls in the right inferior frontal gyrus (IFG). Differences spread to the right supramarginal and temporal cortices during later encoding where, along with the right IFG, they persisted throughout the maintenance period. Limitations This study focused on men with combat-related PTSD using a verbal working memory task. Future studies should evaluate women and the impact of various traumatic experiences using diverse tasks. Conclusion Posttraumatic stress disorder is associated with neurophysiological abnormalities during working memory encoding and maintenance. Veterans with PTSD engaged a bilateral network, including the inferior prefrontal cortices and supramarginal gyri. Right hemispheric neural activity likely reflects compensatory processing, as veterans with PTSD work to maintain accurate performance despite known cognitive deficits associated with the disorder. PMID:26645740

Running Economy: Neuromuscular and Joint Stiffness Contributions in Trained Runners.

PubMed

Tam, Nicholas; Tucker, Ross; Santos-Concejero, Jordan; Prins, Danielle; Lamberts, Robert P

2018-05-29

It is debated whether running biomechanics make good predictors of running economy, with little known information about the neuromuscular and joint stiffness contributions to economical running gait. The aim of this study was to understand the relationship between certain neuromuscular and spatiotemporal biomechanical factors associated with running economy. Thirty trained runners performed a 6-minute constant-speed running set at 3.3 m∙s -1 , where oxygen consumption was assessed. Overground running trials were also performed at 3.3 m∙s -1 to assess kinematics, kinetics and muscle activity. Spatiotemporal gait variables, joint stiffness, pre-activation and stance phase muscle activity (gluteus medius; rectus femoris (RF); biceps femoris(BF); peroneus longus (PL); tibialis anterior (TA); gastrocnemius lateralis and medius (LG and MG) were variables of specific interest and thus determined. Additionally, pre-activation and ground contact of agonist:antagonist co-activation were calculated. More economical runners presented with short ground contact times (r=0.639, p<0.001) and greater strides frequencies (r=-0.630, p<0.001). Lower ankle and greater knee stiffness were associated with lower oxygen consumption (r=0.527, p=0.007 & r=0.384, p=0.043, respectively). Only LG:TA co-activation during stance were associated with lower oxygen cost of transport (r=0.672, p<0.0001). Greater muscle pre-activation and bi-articular muscle activity during stance were associated with more economical runners. Consequently, trained runners who exhibit greater neuromuscular activation prior to and during ground contact, in turn optimise spatiotemporal variables and joint stiffness, will be the most economical runners.

Neuronal cell fate specification by the molecular convergence of different spatio-temporal cues on a common initiator terminal selector gene

PubMed Central

Stratmann, Johannes

2017-01-01

The extensive genetic regulatory flows underlying specification of different neuronal subtypes are not well understood at the molecular level. The Nplp1 neuropeptide neurons in the developing Drosophila nerve cord belong to two sub-classes; Tv1 and dAp neurons, generated by two distinct progenitors. Nplp1 neurons are specified by spatial cues; the Hox homeotic network and GATA factor grn, and temporal cues; the hb -> Kr -> Pdm -> cas -> grh temporal cascade. These spatio-temporal cues combine into two distinct codes; one for Tv1 and one for dAp neurons that activate a common terminal selector feedforward cascade of col -> ap/eya -> dimm -> Nplp1. Here, we molecularly decode the specification of Nplp1 neurons, and find that the cis-regulatory organization of col functions as an integratory node for the different spatio-temporal combinatorial codes. These findings may provide a logical framework for addressing spatio-temporal control of neuronal sub-type specification in other systems. PMID:28414802

Emergent dynamics of spatio-temporal chaos in a heterogeneous excitable medium.

PubMed

Bittihn, Philip; Berg, Sebastian; Parlitz, Ulrich; Luther, Stefan

2017-09-01

Self-organized activation patterns in excitable media such as spiral waves and spatio-temporal chaos underlie dangerous cardiac arrhythmias. While the interaction of single spiral waves with different types of heterogeneity has been studied extensively, the effect of heterogeneity on fully developed spatio-temporal chaos remains poorly understood. We investigate how the complexity and stability properties of spatio-temporal chaos in the Bär-Eiswirth model of excitable media depend on the heterogeneity of the underlying medium. We employ different measures characterizing the chaoticity of the system and find that the spatial arrangement of multiple discrete lower excitability regions has a strong impact on the complexity of the dynamics. Varying the number, shape, and spatial arrangement of the heterogeneities, we observe strong emergent effects ranging from increases in chaoticity to the complete cessation of chaos, contrasting the expectation from the homogeneous behavior. The implications of our findings for the development and treatment of arrhythmias in the heterogeneous cardiac muscle are discussed.

Emergent dynamics of spatio-temporal chaos in a heterogeneous excitable medium

NASA Astrophysics Data System (ADS)

Bittihn, Philip; Berg, Sebastian; Parlitz, Ulrich; Luther, Stefan

2017-09-01

Self-organized activation patterns in excitable media such as spiral waves and spatio-temporal chaos underlie dangerous cardiac arrhythmias. While the interaction of single spiral waves with different types of heterogeneity has been studied extensively, the effect of heterogeneity on fully developed spatio-temporal chaos remains poorly understood. We investigate how the complexity and stability properties of spatio-temporal chaos in the Bär-Eiswirth model of excitable media depend on the heterogeneity of the underlying medium. We employ different measures characterizing the chaoticity of the system and find that the spatial arrangement of multiple discrete lower excitability regions has a strong impact on the complexity of the dynamics. Varying the number, shape, and spatial arrangement of the heterogeneities, we observe strong emergent effects ranging from increases in chaoticity to the complete cessation of chaos, contrasting the expectation from the homogeneous behavior. The implications of our findings for the development and treatment of arrhythmias in the heterogeneous cardiac muscle are discussed.

Glucocorticoid Administration Improves Aberrant Fear-Processing Networks in Spider Phobia

PubMed Central

Nakataki, Masahito; Soravia, Leila M; Schwab, Simon; Horn, Helge; Dierks, Thomas; Strik, Werner; Wiest, Roland; Heinrichs, Markus; de Quervain, Dominique J-F; Federspiel, Andrea; Morishima, Yosuke

2017-01-01

Glucocorticoids reduce phobic fear in patients with anxiety disorders. Previous studies have shown that fear-related activation of the amygdala can be mediated through the visual cortical pathway, which includes the fusiform gyrus, or through other pathways. However, it is not clear which of the pathways that activate the amygdala is responsible for the pathophysiology of a specific phobia and how glucocorticoid treatment alleviates fear processing in these neural networks. We recorded the brain activity with functional magnetic resonance imaging in patients with spider phobia, who received either 20 mg of cortisol or a placebo while viewing pictures of spiders. We also tested healthy participants who did not receive any medication during the same task. We performed dynamic causal modelling (DCM), a connectivity analysis, to examine the effects of cortisol on the networks involved in processing fear and to examine if there was an association between these networks and the symptoms of the phobia. Cortisol administration suppressed the phobic stimuli-related amygdala activity to levels comparable to the healthy participants and reduced subjective phobic fear. The DCM analysis revealed that cortisol administration suppressed the aberrant inputs into the amygdala that did not originate from the visual cortical pathway, but rather from a fast subcortical pathway mediated by the pulvinar nucleus, and suppressed the interactions between the amygdala and fusiform gyrus. This network changes were distinguishable from healthy participants and considered the residual changes under cortisol administration. We also found that the strengths of the aberrant inputs into the amygdala were positively correlated with the severity of spider phobia. This study demonstrates that patients with spider phobia show an aberrant functional connectivity of the amygdala when they are exposed to phobia-related stimuli and that cortisol administration can alleviate this fear-specific neural connectivity. PMID:27644128

Glucocorticoid Administration Improves Aberrant Fear-Processing Networks in Spider Phobia.

PubMed

Nakataki, Masahito; Soravia, Leila M; Schwab, Simon; Horn, Helge; Dierks, Thomas; Strik, Werner; Wiest, Roland; Heinrichs, Markus; de Quervain, Dominique J-F; Federspiel, Andrea; Morishima, Yosuke

2017-01-01

Glucocorticoids reduce phobic fear in patients with anxiety disorders. Previous studies have shown that fear-related activation of the amygdala can be mediated through the visual cortical pathway, which includes the fusiform gyrus, or through other pathways. However, it is not clear which of the pathways that activate the amygdala is responsible for the pathophysiology of a specific phobia and how glucocorticoid treatment alleviates fear processing in these neural networks. We recorded the brain activity with functional magnetic resonance imaging in patients with spider phobia, who received either 20 mg of cortisol or a placebo while viewing pictures of spiders. We also tested healthy participants who did not receive any medication during the same task. We performed dynamic causal modelling (DCM), a connectivity analysis, to examine the effects of cortisol on the networks involved in processing fear and to examine if there was an association between these networks and the symptoms of the phobia. Cortisol administration suppressed the phobic stimuli-related amygdala activity to levels comparable to the healthy participants and reduced subjective phobic fear. The DCM analysis revealed that cortisol administration suppressed the aberrant inputs into the amygdala that did not originate from the visual cortical pathway, but rather from a fast subcortical pathway mediated by the pulvinar nucleus, and suppressed the interactions between the amygdala and fusiform gyrus. This network changes were distinguishable from healthy participants and considered the residual changes under cortisol administration. We also found that the strengths of the aberrant inputs into the amygdala were positively correlated with the severity of spider phobia. This study demonstrates that patients with spider phobia show an aberrant functional connectivity of the amygdala when they are exposed to phobia-related stimuli and that cortisol administration can alleviate this fear-specific neural connectivity.

Intraoperative non-record-keeping usage of anesthesia information management system workstations and associated hemodynamic variability and aberrancies.

PubMed

Wax, David B; Lin, Hung-Mo; Reich, David L

2012-12-01

Anesthesia information management system workstations in the anesthesia workspace that allow usage of non-record-keeping applications could lead to distraction from patient care. We evaluated whether non-record-keeping usage of the computer workstation was associated with hemodynamic variability and aberrancies. Auditing data were collected on eight anesthesia information management system workstations and linked to their corresponding electronic anesthesia records to identify which application was active at any given time during the case. For each case, the periods spent using the anesthesia information management system record-keeping module were separated from those spent using non-record-keeping applications. The variability of heart rate and blood pressure were also calculated, as were the incidence of hypotension, hypertension, and tachycardia. Analysis was performed to identify whether non-record-keeping activity was a significant predictor of these hemodynamic outcomes. Data were analyzed for 1,061 cases performed by 171 clinicians. Median (interquartile range) non-record-keeping activity time was 14 (1, 38) min, representing 16 (3, 33)% of a median 80 (39, 143) min of procedure time. Variables associated with greater non-record-keeping activity included attending anesthesiologists working unassisted, longer case duration, lower American Society of Anesthesiologists status, and general anesthesia. Overall, there was no independent association between non-record-keeping workstation use and hemodynamic variability or aberrancies during anesthesia either between cases or within cases. Anesthesia providers spent sizable portions of case time performing non-record-keeping applications on anesthesia information management system workstations. This use, however, was not independently associated with greater hemodynamic variability or aberrancies in patients during maintenance of general anesthesia for predominantly general surgical and gynecologic procedures.

Chromosomal instability in rodents caused by pollution from Baikonur cosmodrome.

PubMed

Kolumbayeva, Saule; Begimbetova, Dinara; Shalakhmetova, Tamara; Saliev, Timur; Lovinskaya, Anna; Zhunusbekova, Benazir

2014-09-01

An assessment of the health status of ecosystems exposed to man-made pollution is a vital issue for many countries. Particularly it concerns the consequences of contamination caused by the activity of the space industry. Each rocket launch is accompanied by the introduction of parts of the rocket propellant into the environment. This study aims to scrutinize the effect of the components of rocket fuel on the induction of lipid peroxidation and chromosomal aberrations on rodents inhabiting the area exposed to pollution from Baikonur cosmodrome. The results showed the increase of the level of lipid hydroperoxide and malondialdehyde in the livers of Citellus pygmaeus Pallas and Mus musculus L., which indicates an augmentation of free radical activity and DNA damage. The cytogenetic analysis of bone marrow cells revealed that the frequency of chromosomal aberrations was a few times higher in the rodents from contaminated territory. The signs of oxidative stress and high level of chromosomal aberrations indicate the environmental impact of the cosmodrome, and its possible toxic and mutagenic effects on ecosystems.

BAC-FISH assays delineate complex chromosomal rearrangements in a case of post-Chernobyl childhood thyroid cancer

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

Kwan, Johnson; Baumgartner, Adolf; Lu, Chun-Mei

2009-03-09

Structural chromosome aberrations are known hallmarks of many solid tumors. In the papillary form of thyroid cancer (PTC), for example, activation of the receptor tyrosine kinase (RTK) genes, RET and neurotrophic tyrosine kinase receptor type I (NTRK1) by intra- and interchromosomal rearrangements has been suggested as a cause of the disease. However, many phenotypically similar tumors do not carry an activated RET or NTRK-1 gene or express abnormal ret or NTRK-1 transcripts. Thus, we hypothesize that other cellular RTK-type genes are aberrantly expressed in these tumors. Using fluorescence in situ hybridization-based methods, we are studying karyotype changes in a relativelymore » rare subgroup of PTCs, i.e., tumors that arose in children following the 1986 nuclear accident in Chernobyl, Ukraine. Here, we report our technical developments and progress in deciphering complex chromosome aberrations in case S48TK, an aggressively growing PTC cell line, which shows an unusual high number of unbalanced translocations.« less

Detailed spatiotemporal brain mapping of chromatic vision combining high-resolution VEP with fMRI and retinotopy.

PubMed

Pitzalis, Sabrina; Strappini, Francesca; Bultrini, Alessandro; Di Russo, Francesco

2018-03-13

Neuroimaging studies have identified so far, several color-sensitive visual areas in the human brain, and the temporal dynamics of these activities have been separately investigated using the visual-evoked potentials (VEPs). In the present study, we combined electrophysiological and neuroimaging methods to determine a detailed spatiotemporal profile of chromatic VEP and to localize its neural generators. The accuracy of the present co-registration study was obtained by combining standard fMRI data with retinotopic and motion mapping data at the individual level. We found a sequence of occipito activities more complex than that typically reported for chromatic VEPs, including feed-forward and reentrant feedback. Results showed that chromatic human perception arises by the combined activity of at the least five parieto-occipital areas including V1, LOC, V8/VO, and the motion-sensitive dorsal region MT+. However, the contribution of V1 and V8/VO seems dominant because the re-entrant activity in these areas was present more than once (twice in V8/VO and thrice in V1). This feedforward and feedback chromatic processing appears delayed compared with the luminance processing. Associating VEPs and neuroimaging measures, we showed for the first time a complex spatiotemporal pattern of activity, confirming that chromatic stimuli produce intricate interactions of many different brain dorsal and ventral areas. © 2018 Wiley Periodicals, Inc.

WNT signaling controls expression of pro-apoptotic BOK and BAX in intestinal cancer

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

Zeilstra, Jurrit; Joosten, Sander P.J.; Wensveen, Felix M.

Research highlights: {yields} Intestinal adenomas initiated by aberrant activation of the WNT pathway displayed an increased sensitivity to apoptosis. {yields} Expression profiling of apoptosis-related genes in Apc{sup Min/+} mice revealed the differential expression of pro-apoptotic Bok and Bax. {yields} APC-mutant adenomatous crypts in FAP patients showed strongly increased BAX immunoreactivity. {yields} Blocking of {beta}-catenin/TCF-4-mediated signaling in colon cancer cells reduced the expression of BOK and BAX. -- Abstract: In a majority of cases, colorectal cancer is initiated by aberrant activation of the WNT signaling pathway. Mutation of the genes encoding the WNT signaling components adenomatous polyposis coli or {beta}-catenin causesmore » constitutively active {beta}-catenin/TCF-mediated transcription, driving the transformation of intestinal crypts to cancer precursor lesions, called dysplastic aberrant crypt foci. Deregulated apoptosis is a hallmark of adenomatous colon tissue. However, the contribution of WNT signaling to this process is not fully understood. We addressed this role by analyzing the rate of epithelial apoptosis in aberrant crypts and adenomas of the Apc{sup Min/+} mouse model. In comparison with normal crypts and adenomas, aberrant crypts displayed a dramatically increased rate of apoptotic cell death. Expression profiling of apoptosis-related genes along the crypt-villus axis and in Apc mutant adenomas revealed increased expression of two pro-apoptotic Bcl-2 family members in intestinal adenomas, Bok and Bax. Analysis of the colon of familial adenomatous polyposis (FAP) patients along the crypt-to-surface axis, and of dysplastic crypts, corroborated this expression pattern. Disruption of {beta}-catenin/TCF-4-mediated signaling in the colorectal cancer cell line Ls174T significantly decreased BOK and BAX expression, confirming WNT-dependent regulation in intestinal epithelial cells. Our results suggest a feedback mechanism by which uncontrolled epithelial cell proliferation in the stem cell compartment can be counterbalanced by an increased propensity to undergo cell death.« less

Action Direction of Muscle Synergies in Three-Dimensional Force Space

PubMed Central

Hagio, Shota; Kouzaki, Motoki

2015-01-01

Redundancy in the musculoskeletal system was supposed to be simplified by muscle synergies, which modularly organize muscles. To clarify the underlying mechanisms of motor control using muscle synergies, it is important to examine the spatiotemporal contribution of muscle synergies in the task space. In this study, we quantified the mechanical contribution of muscle synergies as considering spatiotemporal correlation between the activation of muscle synergies and endpoint force fluctuations. Subjects performed isometric force generation in the three-dimensional force space. The muscle-weighting vectors of muscle synergies and their activation traces across different trials were extracted from electromyogram data using decomposing technique. We then estimated mechanical contribution of muscle synergies across each trial based on cross-correlation analysis. The contributing vectors were averaged for all trials, and the averaging was defined as action direction (AD) of muscle synergies. As a result, we extracted approximately five muscle synergies. The ADs of muscle synergies mainly depended on the anatomical functions of their weighting muscles. Furthermore, the AD of each muscle indicated the synchronous activation of muscles, which composed of the same muscle synergy. These results provide the spatiotemporal characteristics of muscle synergies as neural basis. PMID:26618156

Action Direction of Muscle Synergies in Three-Dimensional Force Space.

PubMed

Hagio, Shota; Kouzaki, Motoki

2015-01-01

Redundancy in the musculoskeletal system was supposed to be simplified by muscle synergies, which modularly organize muscles. To clarify the underlying mechanisms of motor control using muscle synergies, it is important to examine the spatiotemporal contribution of muscle synergies in the task space. In this study, we quantified the mechanical contribution of muscle synergies as considering spatiotemporal correlation between the activation of muscle synergies and endpoint force fluctuations. Subjects performed isometric force generation in the three-dimensional force space. The muscle-weighting vectors of muscle synergies and their activation traces across different trials were extracted from electromyogram data using decomposing technique. We then estimated mechanical contribution of muscle synergies across each trial based on cross-correlation analysis. The contributing vectors were averaged for all trials, and the averaging was defined as action direction (AD) of muscle synergies. As a result, we extracted approximately five muscle synergies. The ADs of muscle synergies mainly depended on the anatomical functions of their weighting muscles. Furthermore, the AD of each muscle indicated the synchronous activation of muscles, which composed of the same muscle synergy. These results provide the spatiotemporal characteristics of muscle synergies as neural basis.

Millimeter-scale epileptiform spike propagation patterns and their relationship to seizures

PubMed Central

Vanleer, Ann C; Blanco, Justin A; Wagenaar, Joost B; Viventi, Jonathan; Contreras, Diego; Litt, Brian

2016-01-01

Objective Current mapping of epileptic networks in patients prior to epilepsy surgery utilizes electrode arrays with sparse spatial sampling (∼1.0 cm inter-electrode spacing). Recent research demonstrates that sub-millimeter, cortical-column-scale domains have a role in seizure generation that may be clinically significant. We use high-resolution, active, flexible surface electrode arrays with 500 μm inter-electrode spacing to explore epileptiform local field potential spike propagation patterns in two dimensions recorded from subdural micro-electrocorticographic signals in vivo in cat. In this study, we aimed to develop methods to quantitatively characterize the spatiotemporal dynamics of epileptiform activity at high-resolution. Approach We topically administered a GABA-antagonist, picrotoxin, to induce acute neocortical epileptiform activity leading up to discrete electrographic seizures. We extracted features from local field potential spikes to characterize spatiotemporal patterns in these events. We then tested the hypothesis that two dimensional spike patterns during seizures were different from those between seizures. Main results We showed that spatially correlated events can be used to distinguish ictal versus interictal spikes. Significance We conclude that sub-millimeter-scale spatiotemporal spike patterns reveal network dynamics that are invisible to standard clinical recordings and contain information related to seizure-state. PMID:26859260

Millimeter-scale epileptiform spike propagation patterns and their relationship to seizures

NASA Astrophysics Data System (ADS)

Vanleer, Ann C.; Blanco, Justin A.; Wagenaar, Joost B.; Viventi, Jonathan; Contreras, Diego; Litt, Brian

2016-04-01

Objective. Current mapping of epileptic networks in patients prior to epilepsy surgery utilizes electrode arrays with sparse spatial sampling (∼1.0 cm inter-electrode spacing). Recent research demonstrates that sub-millimeter, cortical-column-scale domains have a role in seizure generation that may be clinically significant. We use high-resolution, active, flexible surface electrode arrays with 500 μm inter-electrode spacing to explore epileptiform local field potential (LFP) spike propagation patterns in two dimensions recorded from subdural micro-electrocorticographic signals in vivo in cat. In this study, we aimed to develop methods to quantitatively characterize the spatiotemporal dynamics of epileptiform activity at high-resolution. Approach. We topically administered a GABA-antagonist, picrotoxin, to induce acute neocortical epileptiform activity leading up to discrete electrographic seizures. We extracted features from LFP spikes to characterize spatiotemporal patterns in these events. We then tested the hypothesis that two-dimensional spike patterns during seizures were different from those between seizures. Main results. We showed that spatially correlated events can be used to distinguish ictal versus interictal spikes. Significance. We conclude that sub-millimeter-scale spatiotemporal spike patterns reveal network dynamics that are invisible to standard clinical recordings and contain information related to seizure-state.

Close similarity between spatiotemporal frequency tunings of human cortical responses and involuntary manual following responses to visual motion.

PubMed

Amano, Kaoru; Kimura, Toshitaka; Nishida, Shin'ya; Takeda, Tsunehiro; Gomi, Hiroaki

2009-02-01

Human brain uses visual motion inputs not only for generating subjective sensation of motion but also for directly guiding involuntary actions. For instance, during arm reaching, a large-field visual motion is quickly and involuntarily transformed into a manual response in the direction of visual motion (manual following response, MFR). Previous attempts to correlate motion-evoked cortical activities, revealed by brain imaging techniques, with conscious motion perception have resulted only in partial success. In contrast, here we show a surprising degree of similarity between the MFR and the population neural activity measured by magnetoencephalography (MEG). We measured the MFR and MEG induced by the same motion onset of a large-field sinusoidal drifting grating with changing the spatiotemporal frequency of the grating. The initial transient phase of these two responses had very similar spatiotemporal tunings. Specifically, both the MEG and MFR amplitudes increased as the spatial frequency was decreased to, at most, 0.05 c/deg, or as the temporal frequency was increased to, at least, 10 Hz. We also found in peak latency a quantitative agreement (approximately 100-150 ms) and correlated changes against spatiotemporal frequency changes between MEG and MFR. In comparison with these two responses, conscious visual motion detection is known to be most sensitive (i.e., have the lowest detection threshold) at higher spatial frequencies and have longer and more variable response latencies. Our results suggest a close relationship between the properties of involuntary motor responses and motion-evoked cortical activity as reflected by the MEG.

Expressing freedom and taking liberties: the paradoxes of aberrant science.

PubMed

Little, M

2006-06-01

Complete freedom does not exist, despite people's preparedness to die for it. Scientific freedom is much defended and yet much misunderstood. Scientists have limits imposed on their freedom by the disciplines and discourse communities in which they place themselves. Freedom within these socially constructed constraints needs to be distinguished from taking liberties with the rules and practices that make up these constraints, and validate the activities of special groups within society. Scientists (and the public) perceive taking liberties with science's rules and practices as aberrant science, and they often react punitively. Aberrant science can be broadly examined under four headings: wicked science, naughty science, dysfunctional science, and ideologically unacceptable science. When we examine examples of perceived aberrant science, we find that these categories of "misconduct" are connected and often confused. Scientific freedom needs to be redefined with due regard to current understandings of scientists as human beings facing powerful social pressures to deliver results of a particular kind.

Spatio-temporal variation of seismicity before the 1971 San Fernando earthquake, California

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

Ishida, M.; Kanamori, H.

1977-08-01

The spatio-temporal variation of seismicity prior to the 1971 San Fernando, California, earthquake is studied for the area within 35 km of the epicenter. During the period from 1932 to 1961, the seismicity in this area was relatively low and random. A remarkable NE-SW trending alignment of activity occurred during the period from 1961 to 1964, the period corresponding to the inferred onset of the Palmdale uplift. During the period from 1965 to 1968, the seismicity around the epicentral area became extremely low; no event was located within 13 km from the epicenter. During the period from 1969 to themore » occurrence of the San Fernando earthquake, activity around the epicentral area increased. This activity may be considered to be foreshock activity in a broad sense.« less

Active porous transition towards spatiotemporal control of molecular flow in a crystal membrane

NASA Astrophysics Data System (ADS)

Takasaki, Yuichi; Takamizawa, Satoshi

2015-11-01

Fluidic control is an essential technology widely found in processes such as flood control in land irrigation and cell metabolism in biological tissues. In any fluidic control system, valve function is the key mechanism used to actively regulate flow and miniaturization of fluidic regulation with precise workability will be particularly vital in the development of microfluidic control. The concept of crystal engineering is alternative to processing technology in microstructure construction, as the ultimate microfluidic devices must provide molecular level control. Consequently, microporous crystals can instantly be converted to microfluidic devices if introduced in an active transformability of porous structure and geometry. Here we show that the introduction of a stress-induced martensitic transition mechanism converts a microporous molecular crystal into an active fluidic device with spatiotemporal molecular flow controllability through mechanical reorientation of subnanometre channels.

Ectopic Activation of Wnt/β-Catenin Signaling in Lens Fiber Cells Results in Cataract Formation and Aberrant Fiber Cell Differentiation

PubMed Central

Antosova, Barbora; Smolikova, Jana; Borkovcova, Romana; Strnad, Hynek; Lachova, Jitka; Machon, Ondrej; Kozmik, Zbynek

2013-01-01

The Wnt/β-catenin signaling pathway controls many processes during development, including cell proliferation, cell differentiation and tissue homeostasis, and its aberrant regulation has been linked to various pathologies. In this study we investigated the effect of ectopic activation of Wnt/β-catenin signaling during lens fiber cell differentiation. To activate Wnt/β-catenin signaling in lens fiber cells, the transgenic mouse referred to as αA-CLEF was generated, in which the transactivation domain of β-catenin was fused to the DNA-binding protein LEF1, and expression of the transgene was controlled by αA-crystallin promoter. Constitutive activation of Wnt/β-catenin signaling in lens fiber cells of αA-CLEF mice resulted in abnormal and delayed fiber cell differentiation. Moreover, adult αA-CLEF mice developed cataract, microphthalmia and manifested downregulated levels of γ-crystallins in lenses. We provide evidence of aberrant expression of cell cycle regulators in embryonic lenses of αA-CLEF transgenic mice resulting in the delay in cell cycle exit and in the shift of fiber cell differentiation to the central fiber cell compartment. Our results indicate that precise regulation of the Wnt/β-catenin signaling activity during later stages of lens development is essential for proper lens fiber cell differentiation and lens transparency. PMID:24205179

Repressive but not activating epigenetic modifications are aberrant on the inactive X chromosome in live cloned cattle.

PubMed

Geng-Sheng, Cao; Yu, Gao; Kun, Wang; Fang-Rong, Ding; Ning, Li

2009-08-01

X inactivation is the process of a chromosome-wide silencing of the majority of genes on the X chromosome during early mammalian development. This process may be aberrant in cloned animals. Here we show that repressive modifications, such as methylation of DNA, and the presence of methylated histones, H3K9me2 and H3K27me3, exhibit distinct aberrance on the inactive X chromosome in live clones. In contrast, H3K4me3, an active gene marker, is obviously missing from the inactive X chromosome in all cattle studied. This suggests that the disappearance of active histone modifications (H3K4me3) seems to be more important for X inactivation than deposition of marks associated with heterochromatin (DNA methylation, H3K27me3 and H3K9me2). It also implies that even apparently normal clones may have subtle abnormalities in repressive, but not activating epigenetic modifications on the inactive X when they survive to term. We also found that the histone H3 methylations were enriched and co-localized at q21-31 of the active X chromosome, which may be associated with an abundance of LINE1 repeat elements. © 2009 The Authors. Journal compilation © 2009 Japanese Society of Developmental Biologists.

Spatiotemporal Psychopathology II: How does a psychopathology of the brain's resting state look like? Spatiotemporal approach and the history of psychopathology.

PubMed

Northoff, Georg

2016-01-15

Psychopathology as the investigation and classification of experience, behavior and symptoms in psychiatric patients is an old discipline that ranges back to the end of the 19th century. Since then different approaches to psychopathology have been suggested. Recent investigations showing abnormalities in the brain on different levels raise the question how the gap between brain and psyche, between neural abnormalities and alteration in experience and behavior can be bridged. Historical approaches like descriptive (Jaspers) and structural (Minkoswki) psychopathology as well as the more current phenomenological psychopathology (Paarnas, Fuchs, Sass, Stanghellini) remain on the side of the psyche giving detailed description of the phenomenal level of experience while leaving open the link to the brain. In contrast, the recently introduced Research Domain Classification (RDoC) aims at explicitly linking brain and psyche by starting from so-called 'neuro-behavioral constructs'. How does Spatiotemporal Psychopathology, as demonstrated in the first paper on depression, stand in relation to these approaches? In a nutshell, Spatiotemporal Psychopathology aims to bridge the gap between brain and psyche. Specifically, as demonstrated in depression in the first paper, the focus is on the spatiotemporal features of the brain's intrinsic activity and how they are transformed into corresponding spatiotemporal features in experience on the phenomenal level and behavioral changes, which can well account for the symptoms in these patients. This second paper focuses on some of the theoretical background assumptions in Spatiotemporal Psychopathology by directly comparing it to descriptive, structural, and phenomenological psychopathology as well as to RDoC. Copyright © 2015 Elsevier B.V. All rights reserved.

Caspase 2 in mitotic catastrophe: The terminator of aneuploid and tetraploid cells.

PubMed

Vitale, Ilio; Manic, Gwenola; Castedo, Maria; Kroemer, Guido

2017-01-01

Mitotic catastrophe is an oncosuppressive mechanism that targets cells experiencing defective mitoses via the activation of specific cell cycle checkpoints, regulated cell death pathways and/or cell senescence. This prevents the accumulation of karyotypic aberrations, which otherwise may drive oncogenesis and tumor progression. Here, we summarize experimental evidence confirming the role of caspase 2 (CASP2) as the main executor of mitotic catastrophe, and we discuss the signals that activate CASP2 in the presence of mitotic aberrations. In addition, we summarize the main p53-dependent and -independent effector pathways through which CASP2 limits chromosomal instability and non-diploidy, hence mediating robust oncosuppressive functions.

Long-term stable active mount for reflective optics

NASA Astrophysics Data System (ADS)

Reinlein, C.; Brady, A.; Damm, C.; Mohaupt, M.; Kamm, A.; Lange, N.; Goy, M.

2016-07-01

We report on the development of an active mount with an orthogonal actuator matrix offering a stable shape optimization for gratings or mirrors. We introduce the actuator distribution and calculate the accessible Zernike polynomials from their actuator influence function. Experimental tests show the capability of the device to compensate for aberrations of grating substrates as we report measurements of a 110x105 mm2 and 220x210 mm2 device With these devices, we evaluate the position depending aberrations, long-term stability shape results, and temperature-induced shape variations. Therewith we will discuss potential applications in space telescopes and Earth-based facilities where long-term stability is mandatory.

The Link between Microbial Diversity and Nitrogen Cycling in Marine Sediments Is Modulated by Macrofaunal Bioturbation

PubMed Central

Yazdani Foshtomi, Maryam; Braeckman, Ulrike; Derycke, Sofie; Sapp, Melanie; Van Gansbeke, Dirk; Sabbe, Koen; Willems, Anne; Vincx, Magda; Vanaverbeke, Jan

2015-01-01

Objectives The marine benthic nitrogen cycle is affected by both the presence and activity of macrofauna and the diversity of N-cycling microbes. However, integrated research simultaneously investigating macrofauna, microbes and N-cycling is lacking. We investigated spatio-temporal patterns in microbial community composition and diversity, macrofaunal abundance and their sediment reworking activity, and N-cycling in seven subtidal stations in the Southern North Sea. Spatio-Temporal Patterns of the Microbial Communities Our results indicated that bacteria (total and β-AOB) showed more spatio-temporal variation than archaea (total and AOA) as sedimentation of organic matter and the subsequent changes in the environment had a stronger impact on their community composition and diversity indices in our study area. However, spatio-temporal patterns of total bacterial and β-AOB communities were different and related to the availability of ammonium for the autotrophic β-AOB. Highest bacterial richness and diversity were observed in June at the timing of the phytoplankton bloom deposition, while richness of β-AOB as well as AOA peaked in September. Total archaeal community showed no temporal variation in diversity indices. Macrofauna, Microbes and the Benthic N-Cycle Distance based linear models revealed that, independent from the effect of grain size and the quality and quantity of sediment organic matter, nitrification and N-mineralization were affected by respectively the diversity of metabolically active β-AOB and AOA, and the total bacteria, near the sediment-water interface. Separate models demonstrated a significant and independent effect of macrofaunal activities on community composition and richness of total bacteria, and diversity indices of metabolically active AOA. Diversity of β-AOB was significantly affected by macrofaunal abundance. Our results support the link between microbial biodiversity and ecosystem functioning in marine sediments, and provided broad correlative support for the hypothesis that this relationship is modulated by macrofaunal activity. We hypothesized that the latter effect can be explained by their bioturbating and bio-irrigating activities, increasing the spatial complexity of the biogeochemical environment. PMID:26102286

Temporal relationship between the 2000 Miyake-Kozu seismovolcanic activity and the 2000 Tokai slow-slip event

NASA Astrophysics Data System (ADS)

Kawamura, Masashi; Yamaoka, Koshun

2009-02-01

We investigated the temporal relationship between the two events, namely, the seismovolcanic activity near the Miyakejima and Kozushima islands and the slow-slip event along the plate boundary in the Tokai district. The islands are located on the east of Tokai, and the Tokai slow-slip event was discovered immediately after the large crustal deformation caused by the volcanic activity in the Miyakejima-Kozushima regions ceased. However, the order of occurrence of these events is still controversial and its recognition will help us to understand the tectonic processes of the central part of Japan, where many volcanic and seismic activities occur. For this purpose, we applied the statistical approach (Kawamura, M., Yamaoka, K., 2006. Spatiotemporal characteristics of the displacement field revealed with principal component analysis and the mode-rotation technique, Tectonophys., 419, 55-73), which consists of principal component analysis (PCA) and a mode rotation procedure, to the displacement field provided by the nationwide GPS network (GEONET) in order to obtain the characteristic structures of spatiotemporal crustal deformation caused by the above two events. We divided the time period of analysis into two sections (namely, June 26, 1999 to June 25, 2000 and June 26, 2000 to June 25, 2002) by the day when the magma intrusion occurred beneath the Miyakejima volcano on June 26, 2000. The spatial and temporal modes for the first time period did not indicate any significant spatiotemporal patterns corresponding to the two events. This indicates the absence of episodic crustal deformations during this time period. On the contrary, the modes for the latter time period included the changes caused by these events. The two major modes included the spatiotemporal structures of the first and latter half periods of the Miyake-Kozu seismovolcanic activity. The characteristic pattern of the crustal deformation corresponding to the Tokai slow-slip event was found in the fourth mode, which was prominent after the beginning of the Miyake-Kozu seismovolcanic activity. From these results, we conclude that the crustal deformation caused by the Tokai slow-slip event did not start before the Miyake-Kozu seismovolcanic activity.

Neuronal Cell Fate Specification by the Convergence of Different Spatiotemporal Cues on a Common Terminal Selector Cascade

PubMed Central

Rubio-Ferrera, Irene; Millán-Crespo, Irene; Contero-García, Patricia; Bahrampour, Shahrzad

2016-01-01

Specification of the myriad of unique neuronal subtypes found in the nervous system depends upon spatiotemporal cues and terminal selector gene cascades, often acting in sequential combinatorial codes to determine final cell fate. However, a specific neuronal cell subtype can often be generated in different parts of the nervous system and at different stages, indicating that different spatiotemporal cues can converge on the same terminal selectors to thereby generate a similar cell fate. However, the regulatory mechanisms underlying such convergence are poorly understood. The Nplp1 neuropeptide neurons in the Drosophila ventral nerve cord can be subdivided into the thoracic-ventral Tv1 neurons and the dorsal-medial dAp neurons. The activation of Nplp1 in Tv1 and dAp neurons depends upon the same terminal selector cascade: col>ap/eya>dimm>Nplp1. However, Tv1 and dAp neurons are generated by different neural progenitors (neuroblasts) with different spatiotemporal appearance. Here, we find that the same terminal selector cascade is triggered by Kr/pdm>grn in dAp neurons, but by Antp/hth/exd/lbe/cas in Tv1 neurons. Hence, two different spatiotemporal combinations can funnel into a common downstream terminal selector cascade to determine a highly related cell fate. PMID:27148744

Aberrant activity of NKL homeobox gene NKX3-2 in a T-ALL subset

PubMed Central

Meyer, Corinna; Kaufmann, Maren; Zaborski, Margarete; MacLeod, Roderick A. F.; Drexler, Hans G.

2018-01-01

T-cell acute lymphoblastic leukemia (T-ALL) is a hematopoietic malignancy originating from T-cell progenitors in which differentiation is blocked at early stages. Physiological expression of specific NKL homeobox genes obeys a hematopoietic NKL-code implicated in the process of lymphopoiesis while in differentiated T-cells these genes are silenced. We propose that this developmental expression pattern underlies the observation that NKL homeobox genes are the most ubiquitous group of transcription factors deregulated in T-ALL, including TLX1, TLX3, NKX2-5 and NKX3-1. Here, we describe a novel member of the NKL homeobox gene subclass, NKX3-2 (BAPX1), which is aberrantly activated in 18% of pediatric T-ALL patients analyzed while being normally expressed in developing spleen. Identification of NKX3-2 expression in T-ALL cell line CCRF-CEM qualified these cells to model its deregulation and function in a leukemic context. Genomic and chromosomal analyses demonstrated normal configuration of the NKX3-2 locus at chromosome 4p15, thus excluding cytogenetic dysregulation. Comparative expression profiling analysis of NKX3-2 patient data revealed deregulated activity of BMP- and MAPK-signalling. These candidate pathways were experimentally confirmed to mediate aberrant NKX3-2 expression. We also show that homeobox gene SIX6, plus MIR17HG and GATA3 are downstream targets of NKX3-2 and plausibly contribute to the pathogenesis of this malignancy by suppressing T-cell differentiation. Finally, NKL homeobox gene NKX2-5 was activated by NKX3-2 in CCRF-CEM and by FOXG1 in PEER, representing mutually inhibitory activators of this translocated oncogene. Together, our findings reveal a novel oncogenic NKL homeobox gene subclass member which is aberrantly expressed in a large subset of T-ALL patients and participates in a deregulated gene network likely to arise in developing spleen. PMID:29746601

Aberrant activity of NKL homeobox gene NKX3-2 in a T-ALL subset.

PubMed

Nagel, Stefan; Meyer, Corinna; Kaufmann, Maren; Zaborski, Margarete; MacLeod, Roderick A F; Drexler, Hans G

2018-01-01

T-cell acute lymphoblastic leukemia (T-ALL) is a hematopoietic malignancy originating from T-cell progenitors in which differentiation is blocked at early stages. Physiological expression of specific NKL homeobox genes obeys a hematopoietic NKL-code implicated in the process of lymphopoiesis while in differentiated T-cells these genes are silenced. We propose that this developmental expression pattern underlies the observation that NKL homeobox genes are the most ubiquitous group of transcription factors deregulated in T-ALL, including TLX1, TLX3, NKX2-5 and NKX3-1. Here, we describe a novel member of the NKL homeobox gene subclass, NKX3-2 (BAPX1), which is aberrantly activated in 18% of pediatric T-ALL patients analyzed while being normally expressed in developing spleen. Identification of NKX3-2 expression in T-ALL cell line CCRF-CEM qualified these cells to model its deregulation and function in a leukemic context. Genomic and chromosomal analyses demonstrated normal configuration of the NKX3-2 locus at chromosome 4p15, thus excluding cytogenetic dysregulation. Comparative expression profiling analysis of NKX3-2 patient data revealed deregulated activity of BMP- and MAPK-signalling. These candidate pathways were experimentally confirmed to mediate aberrant NKX3-2 expression. We also show that homeobox gene SIX6, plus MIR17HG and GATA3 are downstream targets of NKX3-2 and plausibly contribute to the pathogenesis of this malignancy by suppressing T-cell differentiation. Finally, NKL homeobox gene NKX2-5 was activated by NKX3-2 in CCRF-CEM and by FOXG1 in PEER, representing mutually inhibitory activators of this translocated oncogene. Together, our findings reveal a novel oncogenic NKL homeobox gene subclass member which is aberrantly expressed in a large subset of T-ALL patients and participates in a deregulated gene network likely to arise in developing spleen.

A phosphatase-independent gain-of-function mutation in PTEN triggers aberrant cell growth in astrocytes through an autocrine IGF-1 loop.

PubMed

Fernández, S; Genis, L; Torres-Alemán, I

2014-08-07

Loss-of-function mutations in the phosphatase PTEN (phosphatase and tensin homolog deleted on chromosome10) contribute to aberrant cell growth in part through upregulation of the mitogenic IGF-1/PI3K/Akt pathway. In turn, this pathway exerts a homeostatic feedback over PTEN. Using mutagenesis analysis to explore a possible impact of this mutual control on astrocyte growth, we found that truncation of the C-terminal region of PTEN (Δ51) associates with a marked increase in NFκB activity, a transcription factor overactivated in astrocyte tumors. Whereas mutations of PTEN are considered to lead to a loss-of-function, PTENΔ51, a truncation that comprises a region frequently mutated in human gliomas, displayed a neomorphic (gain-of-function) activity that was independent of its phosphatase activity. This gain-of-function of PTENΔ51 includes stimulation of IGF-1 synthesis through protein kinase A activation of the IGF-1 promoter. Increased IGF-1 originates an autocrine loop that activates Akt and NFκB. Constitutive activation of NFκB in PTENΔ51-expressing astrocytes leads to aberrant cell growth; astrocytes expressing this mutant PTEN generate colonies in vitro and tumors in vivo. Mutations converting a tumor suppressor such as PTEN into a tumor promoter through a gain-of-function involving IGF-1 production may further our understanding of the role played by this growth factor in glioma growth and help us define druggable targets for personalized therapy.

Overexpression of protein O-fucosyltransferase 1 accelerates hepatocellular carcinoma progression via the Notch signaling pathway

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

Ma, Lijie; Dong, Pingping; Liu, Longzi

Aberrant activation of Notch signaling frequently occurs in liver cancer, and is associated with liver malignancies. However, the mechanisms regulating pathologic Notch activation in hepatocellular carcinoma (HCC) remain unclear. Protein O-fucosyltransferase 1 (Pofut1) catalyzes the addition of O-linked fucose to the epidermal growth factor-like repeats of Notch. In the present study, we detected the expression of Pofut1 in 8 HCC cell lines and 253 human HCC tissues. We reported that Pofut1 was overexpressed in HCC cell lines and clinical HCC tissues, and Pofut1 overexpression clinically correlated with the unfavorable survival and high disease recurrence in HCC. The in vitro assay demonstratedmore » that Pofut1 overexpression accelerated the cell proliferation and migration in HCC cells. Furthermore, Pofut1 overexpression promoted the binding of Notch ligand Dll1 to Notch receptor, and hence activated Notch signaling pathway in HCC cells, indicating that Pofut1 overexpression could be a reason for the aberrant activation of Notch signaling in HCC. Taken together, our findings indicated that an aberrant activated Pofut1-Notch pathway was involved in HCC progression, and blockage of this pathway could be a promising strategy for the therapy of HCC. - Highlights: • Pofut1 overexpression in HCC was correlated with aggressive tumor behaviors. • Pofut1 overexpression in HCC was associated with poor prognosis. • Pofut1 promoted cell proliferation, migration and invasion in hepatoma cells. • Pofut1 activated Notch signaling pathway in hepatoma cells.« less

Wave front sensing for next generation earth observation telescope

NASA Astrophysics Data System (ADS)

Delvit, J.-M.; Thiebaut, C.; Latry, C.; Blanchet, G.

2017-09-01

High resolution observations systems are highly dependent on optics quality and are usually designed to be nearly diffraction limited. Such a performance allows to set a Nyquist frequency closer to the cut off frequency, or equivalently to minimize the pupil diameter for a given ground sampling distance target. Up to now, defocus is the only aberration that is allowed to evolve slowly and that may be inflight corrected, using an open loop correction based upon ground estimation and refocusing command upload. For instance, Pleiades satellites defocus is assessed from star acquisitions and refocusing is done with a thermal actuation of the M2 mirror. Next generation systems under study at CNES should include active optics in order to allow evolving aberrations not only limited to defocus, due for instance to in orbit thermal variable conditions. Active optics relies on aberration estimations through an onboard Wave Front Sensor (WFS). One option is using a Shack Hartmann. The Shack-Hartmann wave-front sensor could be used on extended scenes (unknown landscapes). A wave-front computation algorithm should then be implemented on-board the satellite to provide the control loop wave-front error measure. In the worst case scenario, this measure should be computed before each image acquisition. A robust and fast shift estimation algorithm between Shack-Hartmann images is then needed to fulfill this last requirement. A fast gradient-based algorithm using optical flows with a Lucas-Kanade method has been studied and implemented on an electronic device developed by CNES. Measurement accuracy depends on the Wave Front Error (WFE), the landscape frequency content, the number of searched aberrations, the a priori knowledge of high order aberrations and the characteristics of the sensor. CNES has realized a full scale sensitivity analysis on the whole parameter set with our internally developed algorithm.

[Chromosome banding analysis of peripheral blood lymphocytes stimulated with IL2 and CpG oligonucleotide DSP30 in patients with chronic lymphocytic leukemia].

PubMed

Stěpanovská, K; Vaňková, G; Némethová, V; Tomášiková, L; Smuhařová, P; Divíšková, E; Vallová, V; Kuglík, P; Plevová, K; Oltová, A; Doubek, M; Pospíšilová, S; Mayer, J

2013-01-01

Chromosomal aberrations play an important role as prognostic factors in chronic lymphocytic leukemia (CLL). These aberrations are mostly detected by fluorescent in situ hybridization (FISH), as chromosomal banding analysis has been scarce due to low proliferative activity of malignant B-lymphocytes in vitro. In 2006, a new method using stimulation with IL-2 and CpG oligonucleotide DSP30 for metaphase generation in CLL was published [1]. The objective of our study was to verify the efficacy of stimulation and to evaluate if the method is suitable for routine diagnostics. In total, peripheral blood samples of 369 CLL patients were analyzed in parallel by chromosomal banding analysis and by FISH probes for 13q14, 11q22-23, CEP12 and 17p13. Out of 369 patients, 307 (83%) were successfully stimulated for metaphase generation. Chromosomal aberrations were detected in 243 (79%) out of 307 patients evaluated by chromosomal banding analysis. Other aberrations that are not included into standard FISH panel were detected in patients karyotypes, e.g. del(6q), del(14q), t(14;18)(q32;q21), t(11;14)(q13;q32) and t(18;22)(q21;q11). One hundred and three (42%) patients showed complex aberrant karyotype not detected by FISH analysis. Stimulation with IL-2 and oligonucleotide DSP30 is an efficient method how to induce proliferation of malignant B-lymphocytes and allows detection of a substantial number of chromosomal aberrations in addition to those detected by standard FISH panel. Using this method in routine diagnostics is helpful particularly in identification of patients with complex aberrant karyotype.

Tumor Stiffening, a Key Determinant of Tumor Progression, is Reversed by Nanomaterial-Induced Photothermal Therapy

PubMed Central

Marangon, Iris; Silva, Amanda A. K.; Guilbert, Thomas; Kolosnjaj-Tabi, Jelena; Marchiol, Carmen; Natkhunarajah, Sharuja; Chamming's, Foucault; Ménard-Moyon, Cécilia; Bianco, Alberto; Gennisson, Jean-Luc; Renault, Gilles; Gazeau, Florence

2017-01-01

Tumor stiffening, stemming from aberrant production and organization of extracellular matrix (ECM), has been considered a predictive marker of tumor malignancy, non-invasively assessed by ultrasound shear wave elastography (SWE). Being more than a passive marker, tumor stiffening restricts the delivery of diagnostic and therapeutic agents to the tumor and per se could modulate cellular mechano-signaling, tissue inflammation and tumor progression. Current strategies to modify the tumor extracellular matrix are based on ECM-targeting chemical agents but also showed deleterious systemic effects. On-demand excitable nanomaterials have shown their ability to perturb the tumor microenvironment in a spatiotemporal-controlled manner and synergistically with chemotherapy. Here, we investigated the evolution of tumor stiffness as well as tumor integrity and progression, under the effect of mild hyperthermia and thermal ablation generated by light-exposed multi-walled carbon nanotubes (MWCNTs) in an epidermoid carcinoma mouse xenograft. SWE was used for real-time mapping of the tumor stiffness, both during the two near infrared irradiation sessions and over the days after the treatment. We observed a transient and reversible stiffening of the tumor tissue during laser irradiation, which was lowered at the second session of mild hyperthermia or photoablation. In contrast, over the days following photothermal treatment, the treated tumors exhibited a significant softening together with volume reduction, whereas non-treated growing tumors showed an increase of tumor rigidity. The organization of the collagen matrix and the distribution of CNTs revealed a spatio-temporal correlation between the presence of nanoheaters and the damages on collagen and cells. This study highlights nanohyperthermia as a promising adjuvant strategy to reverse tumor stiffening and normalize the mechanical tumor environment. PMID:28042338

Spatiotemporal control of opioid signaling and behavior.

PubMed

Siuda, Edward R; Copits, Bryan A; Schmidt, Martin J; Baird, Madison A; Al-Hasani, Ream; Planer, William J; Funderburk, Samuel C; McCall, Jordan G; Gereau, Robert W; Bruchas, Michael R

2015-05-20

Optogenetics is now a widely accepted tool for spatiotemporal manipulation of neuronal activity. However, a majority of optogenetic approaches use binary on/off control schemes. Here, we extend the optogenetic toolset by developing a neuromodulatory approach using a rationale-based design to generate a Gi-coupled, optically sensitive, mu-opioid-like receptor, which we term opto-MOR. We demonstrate that opto-MOR engages canonical mu-opioid signaling through inhibition of adenylyl cyclase, activation of MAPK and G protein-gated inward rectifying potassium (GIRK) channels and internalizes with kinetics similar to that of the mu-opioid receptor. To assess in vivo utility, we expressed a Cre-dependent viral opto-MOR in RMTg/VTA GABAergic neurons, which led to a real-time place preference. In contrast, expression of opto-MOR in GABAergic neurons of the ventral pallidum hedonic cold spot led to real-time place aversion. This tool has generalizable application for spatiotemporal control of opioid signaling and, furthermore, can be used broadly for mimicking endogenous neuronal inhibition pathways. Copyright © 2015 Elsevier Inc. All rights reserved.

Analysis of Chromosomal Aberrations after Low and High Dose Rate Gamma Irradiation in ATM or NBS Suppressed Human Fibroblast Cells

NASA Technical Reports Server (NTRS)

Hada, M.; Huff, J. L.; Patel, Z.; Pluth, J. M.; George, K. A.; Cucinotta, F. A.

2009-01-01

A detailed understanding of the biological effects of heavy nuclei is needed for space radiation protection and for cancer therapy. High-LET radiation produces more complex DNA lesions that may be non-repairable or that may require additional processing steps compared to endogenous DSBs, increasing the possibility of misrepair. Interplay between radiation sensitivity, dose, and radiation quality has not been studied extensively. Previously we studied chromosome aberrations induced by low- and high- LET radiation in several cell lines deficient in ATM (ataxia telangactasia mutated; product of the gene that is mutated in ataxia telangiectasia patients) or NBS (nibrin; product of the gene mutated in the Nijmegen breakage syndrome), and gliomablastoma cells that are proficient or lacking in DNA-dependent protein kinase (DNA-PK) activity. We found that the yields of both simple and complex chromosomal aberrations were significantly increased in the DSB repair defective cells compared to normal cells. The increased aberrations observed for the ATM and NBS defective lines was due to a significantly larger quadratic dose-response term compared to normal fibroblasts for both simple and complex aberrations, while the linear dose-response term was significantly higher in NBS cells only for simple exchanges. These results point to the importance of the functions of ATM and NBS in chromatin modifications that function to facilitate correct DSB repair and minimize aberration formation. To further understand the sensitivity differences that were observed in ATM and NBS deficient cells, in this study, chromosomal aberration analysis was performed in normal lung fibroblast cells treated with KU-55933, a specific ATM kinase inhibitor, or Mirin, an MRN complex inhibitor involved in activation of ATM. We are also testing siRNA knockdown of these proteins. Normal and ATM or NBS suppressed cells were irradiated with gamma-rays and chromosomes were collected with a premature chromosome condensation (PCC) technique at the first mitosis post-irradiation. Chromosomes were analyzed using a multicolor fluorescence in-situ hybridization (mFISH) chromosome painting method. Preliminary analysis showed that chromosomal exchanges were increased in the cells treated with the specific ATM inhibitor. Possible cytogenetic signatures of acute and low dose-rate gamma irradiation in ATM or Nibrin deficient and suppressed cells will be discussed.

Spatio-Temporal Constrained Human Trajectory Generation from the PIR Motion Detector Sensor Network Data: A Geometric Algebra Approach

PubMed Central

Yu, Zhaoyuan; Yuan, Linwang; Luo, Wen; Feng, Linyao; Lv, Guonian

2015-01-01

Passive infrared (PIR) motion detectors, which can support long-term continuous observation, are widely used for human motion analysis. Extracting all possible trajectories from the PIR sensor networks is important. Because the PIR sensor does not log location and individual information, none of the existing methods can generate all possible human motion trajectories that satisfy various spatio-temporal constraints from the sensor activation log data. In this paper, a geometric algebra (GA)-based approach is developed to generate all possible human trajectories from the PIR sensor network data. Firstly, the representation of the geographical network, sensor activation response sequences and the human motion are represented as algebraic elements using GA. The human motion status of each sensor activation are labeled using the GA-based trajectory tracking. Then, a matrix multiplication approach is developed to dynamically generate the human trajectories according to the sensor activation log and the spatio-temporal constraints. The method is tested with the MERL motion database. Experiments show that our method can flexibly extract the major statistical pattern of the human motion. Compared with direct statistical analysis and tracklet graph method, our method can effectively extract all possible trajectories of the human motion, which makes it more accurate. Our method is also likely to provides a new way to filter other passive sensor log data in sensor networks. PMID:26729123

Spatio-Temporal Constrained Human Trajectory Generation from the PIR Motion Detector Sensor Network Data: A Geometric Algebra Approach.

PubMed

Yu, Zhaoyuan; Yuan, Linwang; Luo, Wen; Feng, Linyao; Lv, Guonian

2015-12-30

Passive infrared (PIR) motion detectors, which can support long-term continuous observation, are widely used for human motion analysis. Extracting all possible trajectories from the PIR sensor networks is important. Because the PIR sensor does not log location and individual information, none of the existing methods can generate all possible human motion trajectories that satisfy various spatio-temporal constraints from the sensor activation log data. In this paper, a geometric algebra (GA)-based approach is developed to generate all possible human trajectories from the PIR sensor network data. Firstly, the representation of the geographical network, sensor activation response sequences and the human motion are represented as algebraic elements using GA. The human motion status of each sensor activation are labeled using the GA-based trajectory tracking. Then, a matrix multiplication approach is developed to dynamically generate the human trajectories according to the sensor activation log and the spatio-temporal constraints. The method is tested with the MERL motion database. Experiments show that our method can flexibly extract the major statistical pattern of the human motion. Compared with direct statistical analysis and tracklet graph method, our method can effectively extract all possible trajectories of the human motion, which makes it more accurate. Our method is also likely to provides a new way to filter other passive sensor log data in sensor networks.

The Perception of Dynamic and Static Facial Expressions of Happiness and Disgust Investigated by ERPs and fMRI Constrained Source Analysis

PubMed Central

Trautmann-Lengsfeld, Sina Alexa; Domínguez-Borràs, Judith; Escera, Carles; Herrmann, Manfred; Fehr, Thorsten

2013-01-01

A recent functional magnetic resonance imaging (fMRI) study by our group demonstrated that dynamic emotional faces are more accurately recognized and evoked more widespread patterns of hemodynamic brain responses than static emotional faces. Based on this experimental design, the present study aimed at investigating the spatio-temporal processing of static and dynamic emotional facial expressions in 19 healthy women by means of multi-channel electroencephalography (EEG), event-related potentials (ERP) and fMRI-constrained regional source analyses. ERP analysis showed an increased amplitude of the LPP (late posterior positivity) over centro-parietal regions for static facial expressions of disgust compared to neutral faces. In addition, the LPP was more widespread and temporally prolonged for dynamic compared to static faces of disgust and happiness. fMRI constrained source analysis on static emotional face stimuli indicated the spatio-temporal modulation of predominantly posterior regional brain activation related to the visual processing stream for both emotional valences when compared to the neutral condition in the fusiform gyrus. The spatio-temporal processing of dynamic stimuli yielded enhanced source activity for emotional compared to neutral conditions in temporal (e.g., fusiform gyrus), and frontal regions (e.g., ventromedial prefrontal cortex, medial and inferior frontal cortex) in early and again in later time windows. The present data support the view that dynamic facial displays trigger more information reflected in complex neural networks, in particular because of their changing features potentially triggering sustained activation related to a continuing evaluation of those faces. A combined fMRI and EEG approach thus provides an advanced insight to the spatio-temporal characteristics of emotional face processing, by also revealing additional neural generators, not identifiable by the only use of an fMRI approach. PMID:23818974

DNA-Demethylase Regulated Genes Show Methylation-Independent Spatiotemporal Expression Patterns

PubMed Central

Schumann, Ulrike; Lee, Joanne; Kazan, Kemal; Ayliffe, Michael; Wang, Ming-Bo

2017-01-01

Recent research has indicated that a subset of defense-related genes is downregulated in the Arabidopsis DNA demethylase triple mutant rdd (ros1 dml2 dml3) resulting in increased susceptibility to the fungal pathogen Fusarium oxysporum. In rdd plants these downregulated genes contain hypermethylated transposable element sequences (TE) in their promoters, suggesting that this methylation represses gene expression in the mutant and that these sequences are actively demethylated in wild-type plants to maintain gene expression. In this study, the tissue-specific and pathogen-inducible expression patterns of rdd-downregulated genes were investigated and the individual role of ROS1, DML2, and DML3 demethylases in these spatiotemporal regulation patterns was determined. Large differences in defense gene expression were observed between pathogen-infected and uninfected tissues and between root and shoot tissues in both WT and rdd plants, however, only subtle changes in promoter TE methylation patterns occurred. Therefore, while TE hypermethylation caused decreased gene expression in rdd plants it did not dramatically effect spatiotemporal gene regulation, suggesting that this latter regulation is largely methylation independent. Analysis of ros1-3, dml2-1, and dml3-1 single gene mutant lines showed that promoter TE hypermethylation and defense-related gene repression was predominantly, but not exclusively, due to loss of ROS1 activity. These data demonstrate that DNA demethylation of TE sequences, largely by ROS1, promotes defense-related gene expression but does not control spatiotemporal expression in Arabidopsis. Summary: Ros1-mediated DNA demethylation of promoter transposable elements is essential for activation of defense-related gene expression in response to fungal infection in Arabidopsis thaliana. PMID:28894455

Spatio-temporal foreshock activity during stick-slip experiments of large rock samples

NASA Astrophysics Data System (ADS)

Tsujimura, Y.; Kawakata, H.; Fukuyama, E.; Yamashita, F.; Xu, S.; Mizoguchi, K.; Takizawa, S.; Hirano, S.

2016-12-01

Foreshock activity has sometimes been reported for large earthquakes, and has been roughly classified into the following two classes. For shallow intraplate earthquakes, foreshocks occurred in the vicinity of the mainshock hypocenter (e.g., Doi and Kawakata, 2012; 2013). And for intraplate subduction earthquakes, foreshock hypocenters migrated toward the mainshock hypocenter (Kato, et al., 2012; Yagi et al., 2014). To understand how foreshocks occur, it is useful to investigate the spatio-temporal activities of foreshocks in the laboratory experiments under controlled conditions. We have conducted stick-slip experiments by using a large-scale biaxial friction apparatus at NIED in Japan (e.g., Fukuyama et al., 2014). Our previous results showed that stick-slip events repeatedly occurred in a run, but only those later events were preceded by foreshocks. Kawakata et al. (2014) inferred that the gouge generated during the run was an important key for foreshock occurrence. In this study, we proceeded to carry out stick-slip experiments of large rock samples whose interface (fault plane) is 1.5 meter long and 0.5 meter wide. After some runs to generate fault gouge between the interface. In the current experiments, we investigated spatio-temporal activities of foreshocks. We detected foreshocks from waveform records of 3D array of piezo-electric sensors. Our new results showed that more than three foreshocks (typically about twenty) had occurred during each stick-slip event, in contrast to the few foreshocks observed during previous experiments without pre-existing gouge. Next, we estimated the hypocenter locations of the stick-slip events, and found that they were located near the opposite end to the loading point. In addition, we observed a migration of foreshock hypocenters toward the hypocenter of each stick-slip event. This suggests that the foreshock activity observed in our current experiments was similar to that for the interplate earthquakes in terms of the spatio-temporal pattern. This work was supported by NIED research project "Development of monitoring and forecasting technology for crustal activity", JSPS KAKENHI Grant Number 23340131, and MEXT of Japan, under its Earthquake and Volcano Hazards Observation and Research Program.

Bayesian spatiotemporal model of fMRI data using transfer functions.

PubMed

Quirós, Alicia; Diez, Raquel Montes; Wilson, Simon P

2010-09-01

This research describes a new Bayesian spatiotemporal model to analyse BOLD fMRI studies. In the temporal dimension, we describe the shape of the hemodynamic response function (HRF) with a transfer function model. The spatial continuity and local homogeneity of the evoked responses are modelled by a Gaussian Markov random field prior on the parameter indicating activations. The proposal constitutes an extension of the spatiotemporal model presented in a previous approach [Quirós, A., Montes Diez, R. and Gamerman, D., 2010. Bayesian spatiotemporal model of fMRI data, Neuroimage, 49: 442-456], offering more flexibility in the estimation of the HRF and computational advantages in the resulting MCMC algorithm. Simulations from the model are performed in order to ascertain the performance of the sampling scheme and the ability of the posterior to estimate model parameters, as well as to check the model sensitivity to signal to noise ratio. Results are shown on synthetic data and on a real data set from a block-design fMRI experiment. Copyright (c) 2010 Elsevier Inc. All rights reserved.

The Central Italy Seismic Sequence (2016): Spatial Patterns and Dynamic Fingerprints

NASA Astrophysics Data System (ADS)

Suteanu, Cristian; Liucci, Luisa; Melelli, Laura

2018-01-01

The paper investigates spatio-temporal aspects of the seismic sequence that started in Central Italy (Amatrice, Lazio region) in August 2016, causing hundreds of fatalities and producing major damage to settlements. On one hand, scaling properties of the landscape topography are identified and related to geomorphological processes, supporting the identification of preferential spatial directions in tectonic activity and confirming the role of the past tectonic periods and ongoing processes with respect to the driving of the geomorphological evolution of the area. On the other hand, relations between the spatio-temporal evolution of the sequence and the seismogenic fault systems are studied. The dynamic fingerprints of seismicity are established with the help of events thread analysis (ETA), which characterizes anisotropy in spatio-temporal earthquake patterns. ETA confirms the fact that the direction of the seismogenic normal fault-oriented (N)NW-(S)SE is characterized by persistent seismic activity. More importantly, it also highlights the role of the pre-existing compressive structures, Neogenic thrust and transpressive regional fronts, with a trend-oriented (N)NE-(S)SW, in the stress transfer. Both the fractal features of the topographic surface and the dynamic fingerprint of the recent seismic sequence point to the hypothesis of an active interaction between the Quaternary fault systems and the pre-existing compressional structures.

Spatio-temporal source cluster analysis reveals fronto-temporal auditory change processing differences within a shared autistic and schizotypal trait phenotype.

PubMed

Ford, Talitha C; Woods, Will; Crewther, David P

2017-01-01

Social Disorganisation (SD) is a shared autistic and schizotypal phenotype that is present in the subclinical population. Auditory processing deficits, particularly in mismatch negativity/field (MMN/F) have been reported across both spectrum disorders. This study investigates differences in MMN/F cortical spatio-temporal source activity between higher and lower quintiles of the SD spectrum. Sixteen low (9 female) and 19 high (9 female) SD subclinical adults (18-40years) underwent magnetoencephalography (MEG) during an MMF paradigm where standard tones (50ms) were interrupted by infrequent duration deviants (100ms). Spatio-temporal source cluster analysis with permutation testing revealed no difference between the groups in source activation to the standard tone. To the deviant tone however, there was significantly reduced right hemisphere fronto-temporal and insular cortex activation for the high SD group ( p = 0.038). The MMF, as a product of the cortical response to the deviant minus that to the standard, did not differ significantly between the high and low Social Disorganisation groups. These data demonstrate a deficit in right fronto-temporal processing of an auditory change for those with more of the shared SD phenotype, indicating that right fronto-temporal auditory processing may be associated with psychosocial functioning.

Community ecology in 3D: Tensor decomposition reveals spatio-temporal dynamics of large ecological communities.

PubMed

Frelat, Romain; Lindegren, Martin; Denker, Tim Spaanheden; Floeter, Jens; Fock, Heino O; Sguotti, Camilla; Stäbler, Moritz; Otto, Saskia A; Möllmann, Christian

2017-01-01

Understanding spatio-temporal dynamics of biotic communities containing large numbers of species is crucial to guide ecosystem management and conservation efforts. However, traditional approaches usually focus on studying community dynamics either in space or in time, often failing to fully account for interlinked spatio-temporal changes. In this study, we demonstrate and promote the use of tensor decomposition for disentangling spatio-temporal community dynamics in long-term monitoring data. Tensor decomposition builds on traditional multivariate statistics (e.g. Principal Component Analysis) but extends it to multiple dimensions. This extension allows for the synchronized study of multiple ecological variables measured repeatedly in time and space. We applied this comprehensive approach to explore the spatio-temporal dynamics of 65 demersal fish species in the North Sea, a marine ecosystem strongly altered by human activities and climate change. Our case study demonstrates how tensor decomposition can successfully (i) characterize the main spatio-temporal patterns and trends in species abundances, (ii) identify sub-communities of species that share similar spatial distribution and temporal dynamics, and (iii) reveal external drivers of change. Our results revealed a strong spatial structure in fish assemblages persistent over time and linked to differences in depth, primary production and seasonality. Furthermore, we simultaneously characterized important temporal distribution changes related to the low frequency temperature variability inherent in the Atlantic Multidecadal Oscillation. Finally, we identified six major sub-communities composed of species sharing similar spatial distribution patterns and temporal dynamics. Our case study demonstrates the application and benefits of using tensor decomposition for studying complex community data sets usually derived from large-scale monitoring programs.

Electromagnetic deformable mirror for space applications

NASA Astrophysics Data System (ADS)

Kuiper, S.; Doelman, N.; Overtoom, T.; Nieuwkoop, E.; Russchenberg, T.; van Riel, M.; Wildschut, J.; Baeten, M.; Spruit, H.; Brinkers, S.; Human, J.

2017-09-01

To increase the collecting power and to improve the angular imaging resolution, space telescopes are evolving towards larger primary mirrors. The aerial density of the telescope mirrors needs to be kept low, however, to be compatible with the launch requirements. A light-weight (primary) mirror will introduce additional optical aberrations to the system. These may be caused by for instance manufacturing errors, gravity release and thermo-elastic effects. Active Optics (AO) is a key candidate technology to correct for the resultant wave front aberrations [1].

Active CREB1 promotes a malignant TGFβ2 autocrine loop in glioblastoma.

PubMed

Rodón, Laura; Gonzàlez-Juncà, Alba; Inda, María del Mar; Sala-Hojman, Ada; Martínez-Sáez, Elena; Seoane, Joan

2014-10-01

In advanced cancer, including glioblastoma, the TGFβ pathway acts as an oncogenic factor. Some tumors exhibit aberrantly high TGFβ activity, and the mechanisms underlying this phenomenon are not well understood. We have observed that TGFβ can induce TGFβ2, generating an autocrine loop leading to aberrantly high levels of TGFβ2. We identified cAMP-responsive element-binding protein 1 (CREB1) as the critical mediator of the induction of TGFβ2 by TGFβ. CREB1 binds to the TGFB2 gene promoter in cooperation with SMAD3 and is required for TGFβ to activate transcription. Moreover, the PI3K-AKT and RSK pathways regulate the TGFβ2 autocrine loop through CREB1. The levels of CREB1 and active phosphorylated CREB1 correlate with TGFβ2 in glioblastoma. In addition, using patient-derived in vivo models of glioblastoma, we found that CREB1 levels determine the expression of TGFβ2. Our results show that CREB1 can be considered a biomarker to stratify patients for anti-TGFβ treatments and a therapeutic target in glioblastoma. TGFβ is considered a promising therapeutic target, and several clinical trials using TGFβ inhibitors are generating encouraging results. Here, we discerned the molecular mechanisms responsible for the aberrantly high levels of TGFβ2 found in certain tumors, and we propose biomarkers to predict the clinical response to anti-TGFβ therapies. ©2014 American Association for Cancer Research.

Human umbilical cord-derived mesenchymal stem cells protect from hyperoxic lung injury by ameliorating aberrant elastin remodeling in the lung of O2-exposed newborn rat.

PubMed

Hou, Chen; Peng, Danyi; Gao, Li; Tian, Daiyin; Dai, Jihong; Luo, Zhengxiu; Liu, Enmei; Chen, Hong; Zou, Lin; Fu, Zhou

2018-01-08

The incidence and mortality rates of bronchopulmonary dysplasia (BPD) remain very high. Therefore, novel therapies are imminently needed to improve the outcome of this disease. Human umbilical cord-derived mesenchymal stem cells (UC-MSCs) show promising therapeutic effects on oxygen-induced model of BPD. In our experiment, UC-MSCs were intratracheally delivered into the newborn rats exposed to hyperoxia, a well-established BPD model. This study demonstrated that UC-MSCs reduce elastin expression stimulated by 90% O 2 in human lung fibroblasts-a (HLF-a), and inhibit HLF-a transdifferentiation into myofibroblasts. In addition, the therapeutic effects of UC-MSCs in neonatal rats with BPD, UC-MSCs could inhibit lung elastase activity and reduce aberrant elastin expression and deposition in the lung of BPD rats. Overall, this study suggested that UC-MSCs could ameliorate aberrant elastin expression in the lung of hyperoxia-induced BPD model which may be associated with suppressing increased TGFβ1 activation. Copyright © 2017. Published by Elsevier Inc.

Cooperative STAT/NF-κB signaling regulates lymphoma metabolic reprogramming and aberrant GOT2 expression.

PubMed

Feist, Maren; Schwarzfischer, Philipp; Heinrich, Paul; Sun, Xueni; Kemper, Judith; von Bonin, Frederike; Perez-Rubio, Paula; Taruttis, Franziska; Rehberg, Thorsten; Dettmer, Katja; Gronwald, Wolfram; Reinders, Jörg; Engelmann, Julia C; Dudek, Jan; Klapper, Wolfram; Trümper, Lorenz; Spang, Rainer; Oefner, Peter J; Kube, Dieter

2018-04-17

Knowledge of stromal factors that have a role in the transcriptional regulation of metabolic pathways aside from c-Myc is fundamental to improvements in lymphoma therapy. Using a MYC-inducible human B-cell line, we observed the cooperative activation of STAT3 and NF-κB by IL10 and CpG stimulation. We show that IL10 + CpG-mediated cell proliferation of MYC low cells depends on glutaminolysis. By 13 C- and 15 N-tracing of glutamine metabolism and metabolite rescue experiments, we demonstrate that GOT2 provides aspartate and nucleotides to cells with activated or aberrant Jak/STAT and NF-κB signaling. A model of GOT2 transcriptional regulation is proposed, in which the cooperative phosphorylation of STAT3 and direct joint binding of STAT3 and p65/NF-κB to the proximal GOT2 promoter are important. Furthermore, high aberrant GOT2 expression is prognostic in diffuse large B-cell lymphoma underscoring the current findings and importance of stromal factors in lymphoma biology.

Spontaneous and electrically modulated spatiotemporal dynamics of the neocortical slow oscillation and associated local fast activity.

PubMed

Greenberg, Anastasia; Dickson, Clayton T

2013-12-01

The neocortical slow oscillation (SO; ~1Hz) of non-REM sleep and anesthesia reflects synchronized network activity composed of alternating active and silent (ON/OFF) phases at the local network and cellular level. The SO itself shows self-organized spatiotemporal dynamics as it appears to originate at unique foci on each cycle and then propagates across the cortical surface. During sleep, this rhythm is relevant for neuroplastic processes mediating memory consolidation especially since its enhancement by slow, rhythmic electrical fields improves subsequent recall. However, the neurobiological mechanism by which spontaneous or enhanced SO activity might operate on memory traces is unknown. Here we show a series of original results, using cycle to cycle tracking across multiple neocortical sites in urethane anesthetized rats: The spontaneous spatiotemporal dynamics of the SO are complex, showing interfering propagation patterns in the anterior-to-posterior plane. These patterns compete for expression and tend to alternate following phase resets that take place during the silent OFF phase of the SO. Applying sinusoidal electrical field stimulation to the anterior pole of the cerebral cortex progressively entrained local field, gamma, and multi-unit activity at all sites, while disrupting the coordination of endogenous SO activity. Field stimulation also biased propagation in the anterior-to-posterior direction and more notably, enhanced the long-range gamma synchrony between cortical regions. These results are the first to show that changes to slow wave dynamics cause enhancements in high frequency cortico-cortical communication and provide mechanistic clues into how the SO is relevant for sleep-dependent memory consolidation. © 2013.

Immature Spinal Locomotor Output in Children with Cerebral Palsy.

PubMed

Cappellini, Germana; Ivanenko, Yury P; Martino, Giovanni; MacLellan, Michael J; Sacco, Annalisa; Morelli, Daniela; Lacquaniti, Francesco

2016-01-01

Detailed descriptions of gait impairments have been reported in cerebral palsy (CP), but it is still unclear how maturation of the spinal motoneuron output is affected. Spatiotemporal alpha-motoneuron activation during walking can be assessed by mapping the electromyographic activity profiles from several, simultaneously recorded muscles onto the anatomical rostrocaudal location of the motoneuron pools in the spinal cord, and by means of factor analysis of the muscle activity profiles. Here, we analyzed gait kinematics and EMG activity of 11 pairs of bilateral muscles with lumbosacral innervation in 35 children with CP (19 diplegic, 16 hemiplegic, 2-12 years) and 33 typically developing (TD) children (1-12 years). TD children showed a progressive reduction of EMG burst durations and a gradual reorganization of the spatiotemporal motoneuron output with increasing age. By contrast, children with CP showed very limited age-related changes of EMG durations and motoneuron output, as well as of limb intersegmental coordination and foot trajectory control (on both sides for diplegic children and the affected side for hemiplegic children). Factorization of the EMG signals revealed a comparable structure of the motor output in children with CP and TD children, but significantly wider temporal activation patterns in children with CP, resembling the patterns of much younger TD infants. A similar picture emerged when considering the spatiotemporal maps of alpha-motoneuron activation. Overall, the results are consistent with the idea that early injuries to developing motor regions of the brain substantially affect the maturation of the spinal locomotor output and consequently the future locomotor behavior.

Immature Spinal Locomotor Output in Children with Cerebral Palsy

PubMed Central

Cappellini, Germana; Ivanenko, Yury P.; Martino, Giovanni; MacLellan, Michael J.; Sacco, Annalisa; Morelli, Daniela; Lacquaniti, Francesco

2016-01-01

Detailed descriptions of gait impairments have been reported in cerebral palsy (CP), but it is still unclear how maturation of the spinal motoneuron output is affected. Spatiotemporal alpha-motoneuron activation during walking can be assessed by mapping the electromyographic activity profiles from several, simultaneously recorded muscles onto the anatomical rostrocaudal location of the motoneuron pools in the spinal cord, and by means of factor analysis of the muscle activity profiles. Here, we analyzed gait kinematics and EMG activity of 11 pairs of bilateral muscles with lumbosacral innervation in 35 children with CP (19 diplegic, 16 hemiplegic, 2–12 years) and 33 typically developing (TD) children (1–12 years). TD children showed a progressive reduction of EMG burst durations and a gradual reorganization of the spatiotemporal motoneuron output with increasing age. By contrast, children with CP showed very limited age-related changes of EMG durations and motoneuron output, as well as of limb intersegmental coordination and foot trajectory control (on both sides for diplegic children and the affected side for hemiplegic children). Factorization of the EMG signals revealed a comparable structure of the motor output in children with CP and TD children, but significantly wider temporal activation patterns in children with CP, resembling the patterns of much younger TD infants. A similar picture emerged when considering the spatiotemporal maps of alpha-motoneuron activation. Overall, the results are consistent with the idea that early injuries to developing motor regions of the brain substantially affect the maturation of the spinal locomotor output and consequently the future locomotor behavior. PMID:27826251

Isoflurane induced cognitive impairment in aged rats through hippocampal calcineurin/NFAT signaling

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

Ni, Cheng; Li, Zhengqian; Qian, Min

Calcineurin (CaN) over-activation constrains synaptic plasticity and memory formation. Upon CaN activation, NFAT imports into the nucleus and guides its downstream genes, which also affect neuronal and synaptic function. Aberrant CaN/NFAT signaling involves in neurotoxicity and cognitive impairment in neurological disorders such as Alzheimer's disease, but its role in postoperative cognitive dysfunction (POCD) remains uninvestigated. Inhaled anesthetic isoflurane facilitates the development of POCD, and the present study investigated the role of CaN/NFAT signaling in isoflurane induced cognitive impairment of aged rats, and the therapeutic effects of CaN inhibitor cyclosporine A (CsA). The results indicated that hippocampal CaN activity increased andmore » peaked at 6 h after isoflurane exposure, and NFAT, especially NFATc4, imported into the nucleus following CaN activation. Furthermore, phamacological inhibition of CaN by CsA markedly attenuated isoflurane induced aberrant CaN/NFATc4 signaling in the hippocampus, and rescued relevant spatial learning and memory impairment of aged rats. Overall, the study suggests hippocampal CaN/NFAT signaling as the upstream mechanism of isoflurane induced cognitive impairment, and provides potential therapeutic target and possible treatment methods for POCD. - Highlights: • Isoflurane induces hippocampal calcineurin activation. • Isoflurane induces hippocampal NFAT, especially NFATc4, nuclear import. • Cyclosporine A attenuates isoflurane induced aberrant calcineurin/NFAT signaling. • Cyclosporine A rescues isoflurane induced cognitive impairment. • Calcineurin/NFAT signaling is the upstream mechanism of isoflurane induced synaptic dysfunction and cognitive impairment.« less

Innate immune activation in neurodegenerative disease.

PubMed

Heneka, Michael T; Kummer, Markus P; Latz, Eicke

2014-07-01

The triggering of innate immune mechanisms is emerging as a crucial component of major neurodegenerative diseases. Microglia and other cell types in the brain can be activated in response to misfolded proteins or aberrantly localized nucleic acids. This diverts microglia from their physiological and beneficial functions, and leads to their sustained release of pro-inflammatory mediators. In this Review, we discuss how the activation of innate immune signalling pathways - in particular, the NOD-, LRR- and pyrin domain-containing 3 (NLRP3) inflammasome - by aberrant host proteins may be a common step in the development of diverse neurodegenerative disorders. During chronic activation of microglia, the sustained exposure of neurons to pro-inflammatory mediators can cause neuronal dysfunction and contribute to cell death. As chronic neuroinflammation is observed at relatively early stages of neurodegenerative disease, targeting the mechanisms that drive this process may be useful for diagnostic and therapeutic purposes.

Nexus of signaling and endocytosis in oncogenesis driven by non-small cell lung cancer-associated epidermal growth factor receptor mutants

PubMed Central

Chung, Byung Min; Tom, Eric; Zutshi, Neha; Bielecki, Timothy Alan; Band, Vimla; Band, Hamid

2014-01-01

Epidermal growth factor receptor (EGFR) controls a wide range of cellular processes, and aberrant EGFR signaling as a result of receptor overexpression and/or mutation occurs in many types of cancer. Tumor cells in non-small cell lung cancer (NSCLC) patients that harbor EGFR kinase domain mutations exhibit oncogene addiction to mutant EGFR, which confers high sensitivity to tyrosine kinase inhibitors (TKIs). As patients invariably develop resistance to TKIs, it is important to delineate the cell biological basis of mutant EGFR-induced cellular transformation since components of these pathways can serve as alternate therapeutic targets to preempt or overcome resistance. NSCLC-associated EGFR mutants are constitutively-active and induce ligand-independent transformation in nonmalignant cell lines. Emerging data suggest that a number of factors are critical for the mutant EGFR-dependent tumorigenicity, and bypassing the effects of TKIs on these pathways promotes drug resistance. For example, activation of downstream pathways such as Akt, Erk, STAT3 and Src is critical for mutant EGFR-mediated biological processes. It is now well-established that the potency and spatiotemporal features of cellular signaling by receptor tyrosine kinases such as EGFR, as well as the specific pathways activated, is determined by the nature of endocytic traffic pathways through which the active receptors traverse. Recent evidence indicates that NSCLC-associated mutant EGFRs exhibit altered endocytic trafficking and they exhibit reduced Cbl ubiquitin ligase-mediated lysosomal downregulation. More recent work has shown that mutant EGFRs undergo ligand-independent traffic into the endocytic recycling compartment, a behavior that plays a key role in Src pathway activation and oncogenesis. These studies are beginning to delineate the close nexus between signaling and endocytic traffic of EGFR mutants as a key driver of oncogenic processes. Therefore, in this review, we will discuss the links between mutant EGFR signaling and endocytic properties, and introduce potential mechanisms by which altered endocytic properties of mutant EGFRs may alter signaling and vice versa as well as their implications for NSCLC therapy. PMID:25493220

Aberrant expression of NKL homeobox gene HLX in Hodgkin lymphoma.

PubMed

Nagel, Stefan; Pommerenke, Claudia; Meyer, Corinna; Kaufmann, Maren; MacLeod, Roderick A F; Drexler, Hans G

2018-03-06

NKL homeobox genes are basic regulators of cell and tissue differentiation, many acting as oncogenes in T-cell leukemia. Recently, we described an hematopoietic NKL-code comprising six particular NKL homeobox genes expressed in hematopoietic stem cells and lymphoid progenitors, unmasking their physiological roles in the development of these cell types. Hodgkin lymphoma (HL) is a B-cell malignancy showing aberrant activity of several developmental genes resulting in disturbed B-cell differentiation. To examine potential concordances in abnormal lymphoid differentiation of T- and B-cell malignancies we analyzed the expression of the hematopoietic NKL-code associated genes in HL, comprising HHEX, HLX, MSX1, NKX2-3, NKX3-1 and NKX6-3. Our approach revealed aberrant HLX activity in 8 % of classical HL patients and additionally in HL cell line L-540. Accordingly, to identify upstream regulators and downstream target genes of HLX we used L-540 cells as a model and performed chromosome and genome analyses, comparative expression profiling and functional assays via knockdown and overexpression experiments therein. These investigations excluded chromosomal rearrangements of the HLX locus at 1q41 and demonstrated that STAT3 operated directly as transcriptional activator of the HLX gene. Moreover, subcellular analyses showed highly enriched STAT3 protein in the nucleus of L-540 cells which underwent cytoplasmic translocation by repressing deacetylation. Finally, HLX inhibited transcription of B-cell differentiation factors MSX1, BCL11A and SPIB and of pro-apoptotic factor BCL2L11/BIM, thereby suppressing Etoposide-induced cell death. Collectively, we propose that aberrantly expressed NKL homeobox gene HLX is part of a pathological gene network in HL, driving deregulated B-cell differentiation and survival.

Aberrant Hyperconnectivity in the Motor System at Rest Is Linked to Motor Abnormalities in Schizophrenia Spectrum Disorders.

PubMed

Walther, Sebastian; Stegmayer, Katharina; Federspiel, Andrea; Bohlhalter, Stephan; Wiest, Roland; Viher, Petra V

2017-09-01

Motor abnormalities are frequently observed in schizophrenia and structural alterations of the motor system have been reported. The association of aberrant motor network function, however, has not been tested. We hypothesized that abnormal functional connectivity would be related to the degree of motor abnormalities in schizophrenia. In 90 subjects (46 patients) we obtained resting stated functional magnetic resonance imaging (fMRI) for 8 minutes 40 seconds at 3T. Participants further completed a motor battery on the scanning day. Regions of interest (ROI) were cortical motor areas, basal ganglia, thalamus and motor cerebellum. We computed ROI-to-ROI functional connectivity. Principal component analyses of motor behavioral data produced 4 factors (primary motor, catatonia and dyskinesia, coordination, and spontaneous motor activity). Motor factors were correlated with connectivity values. Schizophrenia was characterized by hyperconnectivity in 3 main areas: motor cortices to thalamus, motor cortices to cerebellum, and prefrontal cortex to the subthalamic nucleus. In patients, thalamocortical hyperconnectivity was linked to catatonia and dyskinesia, whereas aberrant connectivity between rostral anterior cingulate and caudate was linked to the primary motor factor. Likewise, connectivity between motor cortex and cerebellum correlated with spontaneous motor activity. Therefore, altered functional connectivity suggests a specific intrinsic and tonic neural abnormality in the motor system in schizophrenia. Furthermore, altered neural activity at rest was linked to motor abnormalities on the behavioral level. Thus, aberrant resting state connectivity may indicate a system out of balance, which produces characteristic behavioral alterations. © The Author 2017. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Aberrant neural networks for the recognition memory of socially relevant information in patients with schizophrenia.

PubMed

Oh, Jooyoung; Chun, Ji-Won; Kim, Eunseong; Park, Hae-Jeong; Lee, Boreom; Kim, Jae-Jin

2017-01-01

Patients with schizophrenia exhibit several cognitive deficits, including memory impairment. Problems with recognition memory can hinder socially adaptive behavior. Previous investigations have suggested that altered activation of the frontotemporal area plays an important role in recognition memory impairment. However, the cerebral networks related to these deficits are not known. The aim of this study was to elucidate the brain networks required for recognizing socially relevant information in patients with schizophrenia performing an old-new recognition task. Sixteen patients with schizophrenia and 16 controls participated in this study. First, the subjects performed the theme-identification task during functional magnetic resonance imaging. In this task, pictures depicting social situations were presented with three words, and the subjects were asked to select the best theme word for each picture. The subjects then performed an old-new recognition task in which they were asked to discriminate whether the presented words were old or new. Task performance and neural responses in the old-new recognition task were compared between the subject groups. An independent component analysis of the functional connectivity was performed. The patients with schizophrenia exhibited decreased discriminability and increased activation of the right superior temporal gyrus compared with the controls during correct responses. Furthermore, aberrant network activities were found in the frontopolar and language comprehension networks in the patients. The functional connectivity analysis showed aberrant connectivity in the frontopolar and language comprehension networks in the patients with schizophrenia, and these aberrations possibly contribute to their low recognition performance and social dysfunction. These results suggest that the frontopolar and language comprehension networks are potential therapeutic targets in patients with schizophrenia.

Plasma DNA aberrations in systemic lupus erythematosus revealed by genomic and methylomic sequencing

PubMed Central

Chan, Rebecca W. Y.; Jiang, Peiyong; Peng, Xianlu; Tam, Lai-Shan; Liao, Gary J. W.; Li, Edmund K. M.; Wong, Priscilla C. H.; Sun, Hao; Chan, K. C. Allen; Chiu, Rossa W. K.; Lo, Y. M. Dennis

2014-01-01

We performed a high-resolution analysis of the biological characteristics of plasma DNA in systemic lupus erythematosus (SLE) patients using massively parallel genomic and methylomic sequencing. A number of plasma DNA abnormalities were found. First, aberrations in measured genomic representations (MGRs) were identified in the plasma DNA of SLE patients. The extent of the aberrations in MGRs correlated with anti-double–stranded DNA (anti-dsDNA) antibody level. Second, the plasma DNA of active SLE patients exhibited skewed molecular size-distribution profiles with a significantly increased proportion of short DNA fragments. The extent of plasma DNA shortening in SLE patients correlated with the SLE disease activity index (SLEDAI) and anti-dsDNA antibody level. Third, the plasma DNA of active SLE patients showed decreased methylation densities. The extent of hypomethylation correlated with SLEDAI and anti-dsDNA antibody level. To explore the impact of anti-dsDNA antibody on plasma DNA in SLE, a column-based protein G capture approach was used to fractionate the IgG-bound and non–IgG-bound DNA in plasma. Compared with healthy individuals, SLE patients had higher concentrations of IgG-bound DNA in plasma. More IgG binding occurs at genomic locations showing increased MGRs. Furthermore, the IgG-bound plasma DNA was shorter in size and more hypomethylated than the non–IgG-bound plasma DNA. These observations have enhanced our understanding of the spectrum of plasma DNA aberrations in SLE and may provide new molecular markers for SLE. Our results also suggest that caution should be exercised when interpreting plasma DNA-based noninvasive prenatal testing and cancer testing conducted for SLE patients. PMID:25427797

Temporal Stability of Rotors and Atrial Activation Patterns in Persistent Human Atrial Fibrillation: A High-Density Epicardial Mapping Study of Prolonged Recordings.

PubMed

Walters, Tomos E; Lee, Geoffrey; Morris, Gwilym; Spence, Steven; Larobina, Marco; Atkinson, Victoria; Antippa, Phillip; Goldblatt, John; Royse, Alistair; O'Keefe, Michael; Sanders, Prashanthan; Morton, Joseph B; Kistler, Peter M; Kalman, Jonathan M

This study aimed to determine the spatiotemporal stability of rotors and other atrial activation patterns over 10 min in longstanding, persistent AF, along with the relationship of rotors to short cycle-length (CL) activity. The prevalence, stability, and mechanistic importance of rotors in human atrial fibrillation (AF) remain unclear. Epicardial mapping was performed in 10 patients undergoing cardiac surgery, with bipolar electrograms recorded over 10 min using a triangular plaque (area: 6.75 cm 2 ; 117 bipoles; spacing: 2.5 mm) applied to the left atrial posterior wall (n = 9) and the right atrial free wall (n = 4). Activations were identified throughout 6 discrete 10-s segments of AF spanning 10 min, and dynamic activation mapping was performed. The distributions of 4,557 generated activation patterns within each mapped region were compared between the 6 segments. The dominant activation pattern was the simultaneous presence of multiple narrow wave fronts (26%). Twelve percent of activations represented transient rotors, seen in 85% of mapped regions with a median duration of 3 rotations. A total of 87% were centered on an area of short CL activity (<100 ms), although such activity had a positive predictive value for rotors of only 0.12. The distribution of activation patterns and wave-front directionality were highly stable over time, with a single dominant pattern within a 10-s AF segment recurring across all 6 segments in 62% of mapped regions. In patients with longstanding, persistent AF, activation patterns are spatiotemporally stable over 10 min. Transient rotors can be demonstrated in the majority of mapped regions, are spatiotemporally associated with short CL activity, and, when recurrent, demonstrate anatomical determinism. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Stress leads to aberrant hippocampal involvement when processing schema-related information.

PubMed

Vogel, Susanne; Kluen, Lisa Marieke; Fernández, Guillén; Schwabe, Lars

2018-01-01

Prior knowledge, represented as a mental schema, has critical impact on how we organize, interpret, and process incoming information. Recent findings indicate that the use of an existing schema is coordinated by the medial prefrontal cortex (mPFC), communicating with parietal areas. The hippocampus, however, is crucial for encoding schema-unrelated information but not for schema-related information. A recent study indicated that stress mediators may affect schema-related memory, but the underlying neural mechanisms are currently unknown. Here, we thus tested the impact of acute stress on neural processing of schema-related information. We exposed healthy participants to a stress or control manipulation before they processed, in the MRI scanner, words related or unrelated to a preexisting schema activated by a specific cue. Participants' memory for the presented material was tested 3-5 d after encoding. Overall, the processing of schema-related information activated the mPFC, the precuneus, and the angular gyrus. Stress resulted in aberrant hippocampal activity and connectivity while participants processed schema-related information. This aberrant engagement of the hippocampus was linked to altered subsequent memory. These findings suggest that stress may interfere with the efficient use of prior knowledge during encoding and may have important practical implications, in particular for educational settings. © 2018 Vogel et al.; Published by Cold Spring Harbor Laboratory Press.

Assessment of both environmental cytotoxicity and trace metal pollution using Populus simonii Carr. as a bioindicator.

PubMed

Sluchyk, Victor; Sluchyk, Iryna; Shyichuk, Alexander

2014-10-01

The level of environmental pollution in the city of Ivano-Frankivsk (Western Ukraine) has been assessed by means of roadside poplar trees as bioindicators. Dividable apical meristem cells of rudimentary leaves were quantitatively analysed for mitotic activity and distribution. Anaphases were further examined for chromosomal aberrations. Male catkins were also examined for sterile pollens. Accumulation of trace elements in vegetative buds was also evaluated in order to reveal source(s) of environmental pollution. Poplar trees growing in the urban environment proved to have increased chromosomal aberrations (up to 4-fold) and increased pollen sterility (up to 4-fold) as well as decreased mitotic activity (by factor 1.5) as compared to control sampling site. The biomarker data correlate moderately with increased (up to 4-fold) concentrations of Ni, Zn, Pb, Cd and Cu in vegetative tissues suggesting that probable cause of the environmental cytotoxicity may be vehicle emissions. The maximum increase in chromosomal aberrations (7-fold) and the minimum mitotic activity (half of the control one) were recorded in poplar trees growing in industrial suburb in vicinity of large cement production plant. Taking in mind insignificant bioaccumulation of trace elements in the industrial suburb, the high environmental toxicity has been ascribed to contamination in cement and asbestos particulates.

Constitutively Active SPAK Causes Hyperkalemia by Activating NCC and Remodeling Distal Tubules.

PubMed

Grimm, P Richard; Coleman, Richard; Delpire, Eric; Welling, Paul A

2017-09-01

Aberrant activation of with no lysine (WNK) kinases causes familial hyperkalemic hypertension (FHHt). Thiazide diuretics treat the disease, fostering the view that hyperactivation of the thiazide-sensitive sodium-chloride cotransporter (NCC) in the distal convoluted tubule (DCT) is solely responsible. However, aberrant signaling in the aldosterone-sensitive distal nephron (ASDN) and inhibition of the potassium-excretory renal outer medullary potassium (ROMK) channel have also been implicated. To test these ideas, we introduced kinase-activating mutations after Lox-P sites in the mouse Stk39 gene, which encodes the terminal kinase in the WNK signaling pathway, Ste20-related proline-alanine-rich kinase (SPAK). Renal expression of the constitutively active (CA)-SPAK mutant was specifically targeted to the early DCT using a DCT-driven Cre recombinase. CA-SPAK mice displayed thiazide-treatable hypertension and hyperkalemia, concurrent with NCC hyperphosphorylation. However, thiazide-mediated inhibition of NCC and consequent restoration of sodium excretion did not immediately restore urinary potassium excretion in CA-SPAK mice. Notably, CA-SPAK mice exhibited ASDN remodeling, involving a reduction in connecting tubule mass and attenuation of epithelial sodium channel (ENaC) and ROMK expression and apical localization. Blocking hyperactive NCC in the DCT gradually restored ASDN structure and ENaC and ROMK expression, concurrent with the restoration of urinary potassium excretion. These findings verify that NCC hyperactivity underlies FHHt but also reveal that NCC-dependent changes in the driving force for potassium secretion are not sufficient to explain hyperkalemia. Instead, a DCT-ASDN coupling process controls potassium balance in health and becomes aberrantly activated in FHHt. Copyright © 2017 by the American Society of Nephrology.

Determination of aberration center of Ronchigram for automated aberration correctors in scanning transmission electron microscopy.

PubMed

Sannomiya, Takumi; Sawada, Hidetaka; Nakamichi, Tomohiro; Hosokawa, Fumio; Nakamura, Yoshio; Tanishiro, Yasumasa; Takayanagi, Kunio

2013-12-01

A generic method to determine the aberration center is established, which can be utilized for aberration calculation and axis alignment for aberration corrected electron microscopes. In this method, decentering induced secondary aberrations from inherent primary aberrations are minimized to find the appropriate axis center. The fitness function to find the optimal decentering vector for the axis was defined as a sum of decentering induced secondary aberrations with properly distributed weight values according to the aberration order. Since the appropriate decentering vector is determined from the aberration values calculated at an arbitrary center axis, only one aberration measurement is in principle required to find the center, resulting in /very fast center search. This approach was tested for the Ronchigram based aberration calculation method for aberration corrected scanning transmission electron microscopy. Both in simulation and in experiments, the center search was confirmed to work well although the convergence to find the best axis becomes slower with larger primary aberrations. Such aberration center determination is expected to fully automatize the aberration correction procedures, which used to require pre-alignment of experienced users. This approach is also applicable to automated aperture positioning. Copyright © 2013 Elsevier B.V. All rights reserved.

Functional link between plasma membrane spatiotemporal dynamics, cancer biology, and dietary membrane-altering agents.

PubMed

Erazo-Oliveras, Alfredo; Fuentes, Natividad R; Wright, Rachel C; Chapkin, Robert S

2018-06-02

The cell plasma membrane serves as a nexus integrating extra- and intracellular components, which together enable many of the fundamental cellular signaling processes that sustain life. In order to perform this key function, plasma membrane components assemble into well-defined domains exhibiting distinct biochemical and biophysical properties that modulate various signaling events. Dysregulation of these highly dynamic membrane domains can promote oncogenic signaling. Recently, it has been demonstrated that select membrane-targeted dietary bioactives (MTDBs) have the ability to remodel plasma membrane domains and subsequently reduce cancer risk. In this review, we focus on the importance of plasma membrane domain structural and signaling functionalities as well as how loss of membrane homeostasis can drive aberrant signaling. Additionally, we discuss the intricacies associated with the investigation of these membrane domain features and their associations with cancer biology. Lastly, we describe the current literature focusing on MTDBs, including mechanisms of chemoprevention and therapeutics in order to establish a functional link between these membrane-altering biomolecules, tuning of plasma membrane hierarchal organization, and their implications in cancer prevention.

Zinc Transporter SLC39A7/ZIP7 Promotes Intestinal Epithelial Self-Renewal by Resolving ER Stress

PubMed Central

Ohashi, Wakana; Kimura, Shunsuke; Iwanaga, Toshihiko; Furusawa, Yukihiro; Irié, Tarou; Izumi, Hironori; Watanabe, Takashi; Hara, Takafumi; Ohara, Osamu; Koseki, Haruhiko; Sato, Toshiro; Robine, Sylvie; Mori, Hisashi; Hattori, Yuichi; Mishima, Kenji; Ohno, Hiroshi; Hase, Koji; Fukada, Toshiyuki

2016-01-01

Zinc transporters play a critical role in spatiotemporal regulation of zinc homeostasis. Although disruption of zinc homeostasis has been implicated in disorders such as intestinal inflammation and aberrant epithelial morphology, it is largely unknown which zinc transporters are responsible for the intestinal epithelial homeostasis. Here, we show that Zrt-Irt-like protein (ZIP) transporter ZIP7, which is highly expressed in the intestinal crypt, is essential for intestinal epithelial proliferation. Mice lacking Zip7 in intestinal epithelium triggered endoplasmic reticulum (ER) stress in proliferative progenitor cells, leading to significant cell death of progenitor cells. Zip7 deficiency led to the loss of Olfm4+ intestinal stem cells and the degeneration of post-mitotic Paneth cells, indicating a fundamental requirement for Zip7 in homeostatic intestinal regeneration. Taken together, these findings provide evidence for the importance of ZIP7 in maintenance of intestinal epithelial homeostasis through the regulation of ER function in proliferative progenitor cells and maintenance of intestinal stem cells. Therapeutic targeting of ZIP7 could lead to effective treatment of gastrointestinal disorders. PMID:27736879

CD4+ Foxp3+ T cells promote aberrant immunoglobulin G production and maintain CD8+ T-cell suppression during chronic liver disease.

PubMed

Tedesco, Dana; Thapa, Manoj; Gumber, Sanjeev; Elrod, Elizabeth J; Rahman, Khalidur; Ibegbu, Chris C; Magliocca, Joseph F; Adams, Andrew B; Anania, Frank; Grakoui, Arash

2017-02-01

Persistent hepatotropic viral infections are a common etiologic agent of chronic liver disease. Unresolved infection can be attributed to nonfunctional intrahepatic CD8+ T-cell responses. In light of dampened CD8 + T-cell responses, liver disease often manifests systemically as immunoglobulin (Ig)-related syndromes due to aberrant B-cell functions. These two opposing yet coexisting phenomena implicate the potential of altered CD4 + T-cell help. Elevated CD4 + forkhead box P3-positive (Foxp3+) T cells were evident in both human liver disease and a mouse model of chemically induced liver injury despite marked activation and spontaneous IgG production by intrahepatic B cells. While this population suppressed CD8 + T-cell responses, aberrant B-cell activities were maintained due to expression of CD40 ligand on a subset of CD4 + Foxp3+ T cells. In vivo blockade of CD40 ligand attenuated B-cell abnormalities in a mouse model of liver injury. A phenotypically similar population of CD4 + Foxp3+, CD40 ligand-positive T cells was found in diseased livers explanted from patients with chronic hepatitis C infection. This population was absent in nondiseased liver tissues and peripheral blood. Liver disease elicits alterations in the intrahepatic CD4 + T-cell compartment that suppress T-cell immunity while concomitantly promoting aberrant IgG mediated manifestations. (Hepatology 2017;65:661-677). © 2016 by the American Association for the Study of Liver Diseases.

Transcranial phase aberration correction using beam simulations and MR-ARFI

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

Vyas, Urvi, E-mail: urvi.vyas@gmail.com; Kaye, Elena; Pauly, Kim Butts

2014-03-15

Purpose: Transcranial magnetic resonance-guided focused ultrasound surgery is a noninvasive technique for causing selective tissue necrosis. Variations in density, thickness, and shape of the skull cause aberrations in the location and shape of the focal zone. In this paper, the authors propose a hybrid simulation-MR-ARFI technique to achieve aberration correction for transcranial MR-guided focused ultrasound surgery. The technique uses ultrasound beam propagation simulations with MR Acoustic Radiation Force Imaging (MR-ARFI) to correct skull-caused phase aberrations. Methods: Skull-based numerical aberrations were obtained from a MR-guided focused ultrasound patient treatment and were added to all elements of the InSightec conformal bone focusedmore » ultrasound surgery transducer during transmission. In the first experiment, the 1024 aberrations derived from a human skull were condensed into 16 aberrations by averaging over the transducer area of 64 elements. In the second experiment, all 1024 aberrations were applied to the transducer. The aberrated MR-ARFI images were used in the hybrid simulation-MR-ARFI technique to find 16 estimated aberrations. These estimated aberrations were subtracted from the original aberrations to result in the corrected images. Each aberration experiment (16-aberration and 1024-aberration) was repeated three times. Results: The corrected MR-ARFI image was compared to the aberrated image and the ideal image (image with zero aberrations) for each experiment. The hybrid simulation-MR-ARFI technique resulted in an average increase in focal MR-ARFI phase of 44% for the 16-aberration case and 52% for the 1024-aberration case, and recovered 83% and 39% of the ideal MR-ARFI phase for the 16-aberrations and 1024-aberration case, respectively. Conclusions: Using one MR-ARFI image and noa priori information about the applied phase aberrations, the hybrid simulation-MR-ARFI technique improved the maximum MR-ARFI phase of the beam's focus.« less

Prediction of Spatiotemporal Patterns of Neural Activity from Pairwise Correlations

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

Marre, O.; El Boustani, S.; Fregnac, Y.

We designed a model-based analysis to predict the occurrence of population patterns in distributed spiking activity. Using a maximum entropy principle with a Markovian assumption, we obtain a model that accounts for both spatial and temporal pairwise correlations among neurons. This model is tested on data generated with a Glauber spin-glass system and is shown to correctly predict the occurrence probabilities of spatiotemporal patterns significantly better than Ising models only based on spatial correlations. This increase of predictability was also observed on experimental data recorded in parietal cortex during slow-wave sleep. This approach can also be used to generate surrogatesmore » that reproduce the spatial and temporal correlations of a given data set.« less

Regulation of STATs by polycystin-1 and their role in polycystic kidney disease.

PubMed

Weimbs, Thomas; Olsan, Erin E; Talbot, Jeffrey J

2013-04-01

Autosomal-dominant polycystic kidney disease (ADPKD) is a common genetic disease caused by mutations in the gene coding for polycystin-1 (PC1). PC1 can regulate STAT transcription factors by a novel, dual mechanism. STAT3 and STAT6 are aberrantly activated in renal cysts. Genetic and pharmacological approaches to inhibit STAT3 or STAT6 have led to promising results in ADPKD mouse models. Here, we review current findings that lead to a model of PC1 as a key regulator of STAT signaling in renal tubule cells. We discuss how PC1 may orchestrate appropriate epithelial responses to renal injury, and how this system may lead to aberrant STAT activation in ADPKD thereby causing inappropriate activation of tissue repair programs that culminate in renal cyst growth and fibrosis.

[The chiral mutagens: cytogenetic effects on higher plants].

PubMed

Morgun, V V; Larchenko, E A; Kostianovskiĭ, R G; Keterinchuk, A M

2011-01-01

The paper covers investigation of cytogenetic activity of chiral mutagens and their specific effects on the plant cells chromosomes of soft winter wheat (Triticum aestivum L.). Comparative analysis of cytogenetic activity of chiral NEU: S(+)1-N-nitroso- 1-N-methyl-3-N-sec-buthylureas (S(+)NMsBU) and R(-)1-N-nitroso- 1N-methyl-3-Nsec-buthylureas (R(-)NMsBU) on winter wheat was performed. As it was shown by the frequency of chromosomal aberrations the S(+) stereoisomer was twice more active than R(-). In addition to typical anaphase aberrations (fragments, bridges, lagging chromosomes) the numerous mitosis pathologies were revealed - K-mitoses, hyperspiralization and despiralization of chromosomes, unequal allocation of chromosomes between the daughter nuclei, mass fragmentation, nondisjunction and chromosome adhesion, three-pole mitoses, etc. Neither of the mentioned pathologies was observed under the action of NEU and gamma-rays.

Deformable mirror-based optical design of dynamic local athermal longwave infrared optical systems

NASA Astrophysics Data System (ADS)

Shen, Benlan; Chang, Jun; Niu, Yajun; Chen, Weilin; Ji, Zhongye

2018-07-01

This paper presents a dynamic local athermalisation method for longwave infrared (LWIR) optical systems; the proposed design uses a deformable mirror and is based on active optics theory. A local athermal LWIR optical system is designed as an example. The deformable mirror is tilted by 45° near the exit pupil of the system. The thermal aberrations are corrected by the deformable mirror for the local athermal field of view (FOV) that ranges from -40 °C to 80 °C. The types of thermal aberrations are analysed. Simulated results show that the local athermal LWIR optical system can effectively detect targets in the region of interest within a large FOV and correct thermal aberrations in actual working environments in real time. The system has numerous potential applications in infrared detection and tracking, surveillance and remote sensing.

PKCδ activated by c-MET enhances infiltration of human glioblastoma cells through NOTCH2 signaling

PubMed Central

Kang, Seok-Gu; Kim, Rae-Kwon; Cui, Yan-Hong; Lee, Hae-June; Kim, Min-Jung; Lee, Jae-Seong; Kim, In-Gyu; Suh, Yongjoon; Lee, Su-Jae

2016-01-01

Poor prognosis of glioblastoma (GBM) is attributable to the propensity of tumor cells to infiltrate into the brain parenchyma. Protein kinase C (PKC) isozymes are highly expressed or aberrantly activated in GBM. However, how this signaling node translates to GBM cell invasiveness remains unknown. Here, we report that among PKC isoforms, PKCδ is strongly associated with infiltration of GBM cells. Notably, PKCδ enhanced Tyr418 phosphorylation of the non-receptor tyrosine kinase SRC, which in turn activated STAT3 and subsequent NOTCH2 signaling, ultimately leading to GBM cell invasiveness. Furthermore, we showed that PKCδ was aberrantly activated in GBM cells by c-MET, a receptor tyrosine kinase hyperactivated in GBM. In agreement, inhibition either component in the c-MET/PKCδ/SRC/STAT3 signaling axis effectively blocked the NOTCH2 signaling and invasiveness of GBM cells. Taken together, our findings shed a light on the signaling mechanisms behind the constitutive activation of PKCδ signaling in GBM. PMID:26700818

Chromosome aberration and environmental physical activity: Down syndrome and solar and cosmic ray activity, Israel, 1990-2000

NASA Astrophysics Data System (ADS)

Stoupel, Eliahu G.; Frimer, Helena; Appelman, Zvi; Ben-Neriah, Ziva; Dar, Hanna; Fejgin, Moshe D.; Gershoni-Baruch, Ruth; Manor, Esther; Barkai, Gad; Shalev, Stavit; Gelman-Kohan, Zully; Reish, Orit; Lev, Dorit; Davidov, Bella; Goldman, Boleslaw; Shohat, Mordechai

2005-09-01

The possibility that environmental effects are associated with chromosome aberrations and various congenital pathologies has been discussed previously. Recent advances in the collection and computerization of data make studying these potential associations more feasible. The aim of this study was to investigate a possible link between the number of Down syndrome (DS) cases detected prenatally or at birth yearly in Israel over a 10-year period compared with the levels of solar and cosmic ray activity 1 year before the detection or birth of each affected child. Information about 1,108,449 births was collected for the years 1990-2000, excluding 1991, when data were unavailable. A total of 1,310 cases of DS were detected prenatally or at birth—138 in the non-Jewish community and 1,172 in the Jewish population. Solar activity indices—sunspot number and solar radio flux 2,800 MHz at 10.7 cm wavelength for 1989-1999—were compared with the number of DS cases detected. Pearson correlation coefficients (r) and their probabilities (P) were established for the percentage of DS cases in the whole population. There was a significant inverse correlation between the indices of solar activity and the number of cases of DS detected—r=-0.78, P=0.008 for sunspot number and r=-0.76, P=0.01 for solar flux. The possibility that cosmophysical factors inversely related to solar activity play a role in the pathogenesis of chromosome aberrations should be considered. We have confirmed a strong trend towards an association between the cosmic ray activity level and the incidence of DS.

Systemic morphine treatment induces changes in firing patterns and responses of nociceptive afferent fibers in mouse glabrous skin

PubMed Central

Hogan, Dale; Baker, Alyssa L.; Morón, Jose A.; Carlton, Susan M.

2013-01-01

Patients receiving opioids for pain may experience decreased effectiveness of the drug and even abnormal pain sensitivity – either hyperalgesia and/or allodynia. We hypothesize that peripheral nociceptor hyperexcitability contributes to opioid-induced hyperalgesia and test this using an in vitro mouse glabrous skin-nerve preparation. Mice were injected i.p. with escalating doses of morphine (5, 8, 10, 15 mg/kg) or saline every 12 h for 48 h and sacrificed ~12 h following the last injection. Receptive fields of nociceptors were tested for mechanical, heat, and cold sensitivity. Activity was also measured during an initial 2 min period and during 5 min periods between stimuli. Aberrant activity was common in fibers from morphine-treated mice but rare in salinetreated mice. Resting background activity was elevated in C-fibers from morphinetreated mice. Both C- and Aδ -fibers had afterdischarge in response to mechanical, heat and/or cold stimulation of the skin as well as spontaneous, unevoked activity. Compared to saline, morphine treatment increased the proportion of fibers displaying polymodal rather than mechanical-only responses. A significant increase in Aδ-mechanoreceptive fibers responding to cold accounted for most of this change. In agreement with this, morphine-treated mice showed increased sensitivity in the cold tail flick test. In morphine-treated mice, aberrant activity and hyperexcitability of nociceptors could contribute to increased pain sensitivity. Importantly, this activity is likely driving central sensitization, a phenomenon contributing to abnormal sensory processing and chronic pain. If similar changes occur in human patients, aberrant nociceptor activity is likely to be interpreted as pain, and could contribute to opioid-induced hyperalgesia. PMID:23711478

Adaptive Optics Analysis of Visual Benefit with Higher-order Aberrations Correction of Human Eye - Poster Paper

NASA Astrophysics Data System (ADS)

Xue, Lixia; Dai, Yun; Rao, Xuejun; Wang, Cheng; Hu, Yiyun; Liu, Qian; Jiang, Wenhan

2008-01-01

Higher-order aberrations correction can improve visual performance of human eye to some extent. To evaluate how much visual benefit can be obtained with higher-order aberrations correction we developed an adaptive optics vision simulator (AOVS). Dynamic real time optimized modal compensation was used to implement various customized higher-order ocular aberrations correction strategies. The experimental results indicate that higher-order aberrations correction can improve visual performance of human eye comparing with only lower-order aberration correction but the improvement degree and higher-order aberration correction strategy are different from each individual. Some subjects can acquire great visual benefit when higher-order aberrations were corrected but some subjects acquire little visual benefit even though all higher-order aberrations were corrected. Therefore, relative to general lower-order aberrations correction strategy, customized higher-order aberrations correction strategy is needed to obtain optimal visual improvement for each individual. AOVS provides an effective tool for higher-order ocular aberrations optometry for customized ocular aberrations correction.

The 5-HT2A/1A agonist psilocybin disrupts modal object completion associated with visual hallucinations.

PubMed

Kometer, Michael; Cahn, B Rael; Andel, David; Carter, Olivia L; Vollenweider, Franz X

2011-03-01

Recent findings suggest that the serotonergic system and particularly the 5-HT2A/1A receptors are implicated in visual processing and possibly the pathophysiology of visual disturbances including hallucinations in schizophrenia and Parkinson's disease. To investigate the role of 5-HT2A/1A receptors in visual processing the effect of the hallucinogenic 5-HT2A/1A agonist psilocybin (125 and 250 μg/kg vs. placebo) on the spatiotemporal dynamics of modal object completion was assessed in normal volunteers (n = 17) using visual evoked potential recordings in conjunction with topographic-mapping and source analysis. These effects were then considered in relation to the subjective intensity of psilocybin-induced visual hallucinations quantified by psychometric measurement. Psilocybin dose-dependently decreased the N170 and, in contrast, slightly enhanced the P1 component selectively over occipital electrode sites. The decrease of the N170 was most apparent during the processing of incomplete object figures. Moreover, during the time period of the N170, the overall reduction of the activation in the right extrastriate and posterior parietal areas correlated positively with the intensity of visual hallucinations. These results suggest a central role of the 5-HT2A/1A-receptors in the modulation of visual processing. Specifically, a reduced N170 component was identified as potentially reflecting a key process of 5-HT2A/1A receptor-mediated visual hallucinations and aberrant modal object completion potential. Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Chlorpyrifos-Oxon Disrupts Zebrafish Axonal Growth and Motor Behavior

PubMed Central

Yang, Dongren; Lauridsen, Holly; Buels, Kalmia; Chi, Lai-Har; La Du, Jane; Bruun, Donald A.; Olson, James R.; Tanguay, Robert L.; Lein, Pamela J.

2011-01-01

Axonal morphology is a critical determinant of neuronal connectivity, and perturbation of the rate or extent of axonal growth during development has been linked to neurobehavioral deficits in animal models and humans. We previously demonstrated that the organophosphorus pesticide (OP) chlorpyrifos (CPF) inhibits axonal growth in cultured neurons. In this study, we used a zebrafish model to determine whether CPF, its oxon metabolite (CPFO), or the excreted metabolite trichloro-2-pyridinol (TCPy) alter spatiotemporal patterns of axonal growth in vivo. Static waterborne exposure to CPFO, but not CPF or TCPy, at concentrations ≥ 0.03μM from 24- to 72-h post fertilization significantly inhibited acetylcholinesterase, and high-performance liquid chromatography detected significantly more TCPy in zebrafish exposed to 0.1μM CPFO versus 1.0μM CPF. These data suggest that zebrafish lack the metabolic enzymes to activate CPF during these early developmental stages. Consistent with this, CPFO, but not CPF, significantly inhibited axonal growth of sensory neurons, primary motoneurons, and secondary motoneurons at concentrations ≥ 0.1μM. Secondary motoneurons were the most sensitive to axonal growth inhibition by CPFO, which was observed at concentrations that did not cause mortality, gross developmental defects, or aberrant somatic muscle differentiation. CPFO effects on axonal growth correlated with adverse effects on touch-induced swimming behavior, suggesting the functional relevance of these structural changes. These data suggest that altered patterns of neuronal connectivity contribute to the developmental neurotoxicity of CPF and demonstrate the relevance of zebrafish as a model for studying OP developmental neurotoxicity. PMID:21346248

Community ecology in 3D: Tensor decomposition reveals spatio-temporal dynamics of large ecological communities

PubMed Central

Lindegren, Martin; Denker, Tim Spaanheden; Floeter, Jens; Fock, Heino O.; Sguotti, Camilla; Stäbler, Moritz; Otto, Saskia A.; Möllmann, Christian

2017-01-01

Understanding spatio-temporal dynamics of biotic communities containing large numbers of species is crucial to guide ecosystem management and conservation efforts. However, traditional approaches usually focus on studying community dynamics either in space or in time, often failing to fully account for interlinked spatio-temporal changes. In this study, we demonstrate and promote the use of tensor decomposition for disentangling spatio-temporal community dynamics in long-term monitoring data. Tensor decomposition builds on traditional multivariate statistics (e.g. Principal Component Analysis) but extends it to multiple dimensions. This extension allows for the synchronized study of multiple ecological variables measured repeatedly in time and space. We applied this comprehensive approach to explore the spatio-temporal dynamics of 65 demersal fish species in the North Sea, a marine ecosystem strongly altered by human activities and climate change. Our case study demonstrates how tensor decomposition can successfully (i) characterize the main spatio-temporal patterns and trends in species abundances, (ii) identify sub-communities of species that share similar spatial distribution and temporal dynamics, and (iii) reveal external drivers of change. Our results revealed a strong spatial structure in fish assemblages persistent over time and linked to differences in depth, primary production and seasonality. Furthermore, we simultaneously characterized important temporal distribution changes related to the low frequency temperature variability inherent in the Atlantic Multidecadal Oscillation. Finally, we identified six major sub-communities composed of species sharing similar spatial distribution patterns and temporal dynamics. Our case study demonstrates the application and benefits of using tensor decomposition for studying complex community data sets usually derived from large-scale monitoring programs. PMID:29136658

Indicators of drug-seeking aberrant behaviours: the feasibility of use in observational post-marketing cohort studies for risk management.

PubMed

Layton, Deborah; Osborne, Vicki; Al-Shukri, Mohammad; Shakir, Saad A W

2014-08-01

Problematic prescription drug use is reflected by or associated with drug-seeking aberrant behaviours. Research gaps include lack of post-marketing evidence and instruments. As part of the pharmacovigilance requirements, a risk management plan was developed for fentanyl buccal tablets (FEBT) by the manufacturer, with an additional pharmacovigilance activity requested by the regulatory authority, to investigate the risks of misuse, abuse, criminal use, off-label use and accidental exposure to FEBT after the product became commercially available. A Modified Prescription-Event Monitoring (M-PEM), observational, post-authorisation safety surveillance (PASS) study was conducted, with an overall aim to examine the use of FEBT in relation to their safety as prescribed in primary care in England. One of the exploratory objectives included estimating the prevalence of aberrant behaviours during FEBT treatment. To determine the feasibility of estimating the prevalence of risk factors associated with dependence on starting treatment and aberrant behaviours in patients during treatment with a prototypical abuse liable substance (fentanyl), as based on the application of an existing index (the Chabal criteria). Data were collected as part of the M-PEM PASS study; exposure and outcome data (including risk factors for dependence and aberrant behaviours based on behavioural not clinical manifestations) were derived from questionnaires sent to primary care physicians in England during April 2008 to June 2011. For the exploratory objective of interest, descriptive statistics and simple (non-weighted) risk scores were constructed on aggregate counts (score ≥3 considered 'high-risk'). Supplementary analyses explored the relationship between the two indices and the characteristics of patients with aberrant behaviours and those without (crude odds ratios plus 95% confidence interval (CI) were calculated). In a cohort of 551 patients, the prevalence of at least one pre-existing risk factor for dependence was 26% (n = 145), whilst the frequency of aberrant behaviours observed during treatment was 8% (n = 46). Patients with aberrant behaviours had several different characteristics to patients without. The two indices were associated (χ (2) df (20) = 58.72, p < 0.001), but a high-dependence risk-factor score provided a poor indication of high aberrant behaviour risk; the area under the receiver operating characteristic curve was 0.58 (95% CI 0.41, 0.74). Study limitations included subjectivity in relation to physicians identifying aberrant behaviours, and under-reporting thereof in PASS observational study designs. The presence of these criteria does not confirm misuse, but should be considered as a signal of problematic opioid misuse, which requires investigation. Further research is needed to develop a more robust analytical construct. In this PASS study, the prevalence of at least one pre-existing risk factor for dependence was 26%, whilst the frequency of aberrant behaviours observed during treatment was 8%. Patients with aberrant behaviours had several different characteristics to patients without. This study demonstrates the feasibility of the systematic collection of physician reports of risk factors for dependence and aberrant behaviours to facilitate the development of risk scores, using these reports to support the post-marketing risk management of products with misuse potential.

Stress-Induced CDK5 Activation Disrupts Axonal Transport via Lis1/Ndel1/Dynein.

PubMed

Klinman, Eva; Holzbaur, Erika L F

2015-07-21

Axonal transport is essential for neuronal function, and defects in transport are associated with multiple neurodegenerative diseases. Aberrant cyclin-dependent kinase 5 (CDK5) activity, driven by the stress-induced activator p25, also is observed in these diseases. Here we show that elevated CDK5 activity increases the frequency of nonprocessive events for a range of organelles, including lysosomes, autophagosomes, mitochondria, and signaling endosomes. Transport disruption induced by aberrant CDK5 activation depends on the Lis1/Ndel1 complex, which directly regulates dynein activity. CDK5 phosphorylation of Ndel1 favors a high affinity Lis1/Ndel/dynein complex that blocks the ATP-dependent release of dynein from microtubules, inhibiting processive motility of dynein-driven cargo. Similar transport defects observed in neurons from a mouse model of amyotrophic lateral sclerosis are rescued by CDK5 inhibition. Together, these studies identify CDK5 as a Lis1/Ndel1-dependent regulator of transport in stressed neurons, and suggest that dysregulated CDK5 activity contributes to the transport deficits observed during neurodegeneration. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

TGF-{beta}-stimulated aberrant expression of class III {beta}-tubulin via the ERK signaling pathway in cultured retinal pigment epithelial cells

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

Chung, Eun Jee; Chun, Ji Na; Jung, Sun-Ah

2011-11-18

Highlights: Black-Right-Pointing-Pointer TGF-{beta} induces aberrant expression of {beta}III in RPE cells via the ERK pathway. Black-Right-Pointing-Pointer TGF-{beta} increases O-GlcNAc modification of {beta}III in RPE cells. Black-Right-Pointing-Pointer Mature RPE cells have the capacity to express a neuron-associated gene by TGF-{beta}. -- Abstract: The class III {beta}-tubulin isotype ({beta}{sub III}) is expressed exclusively by neurons within the normal human retina and is not present in normal retinal pigment epithelial (RPE) cells in situ or in the early phase of primary cultures. However, aberrant expression of class III {beta}-tubulin has been observed in passaged RPE cells and RPE cells with dedifferentiated morphology inmore » pathologic epiretinal membranes from idiopathic macular pucker, proliferative vitreoretinopathy (PVR) and proliferative diabetic retinopathy (PDR). Transforming growth factor-{beta} (TGF-{beta}) has been implicated in dedifferentiation of RPE cells and has a critical role in the development of proliferative vitreoretinal diseases. Here, we investigated the potential effects of TGF-{beta} on the aberrant expression of class III {beta}-tubulin and the intracellular signaling pathway mediating these changes. TGF-{beta}-induced aberrant expression and O-linked-{beta}-N-acetylglucosamine (O-GlcNac) modification of class III {beta}-tubulin in cultured RPE cells as determined using Western blotting, RT-PCR and immunocytochemistry. TGF-{beta} also stimulated phosphorylation of ERK. TGF-{beta}-induced aberrant expression of class III {beta}-tubulin was significantly reduced by pretreatment with U0126, an inhibitor of ERK phosphorylation. Our findings indicate that TGF-{beta} stimulated aberrant expression of class III {beta}-tubulin via activation of the ERK signaling pathway. These data demonstrate that mature RPE cells have the capacity to express a neuron-associated gene in response to TGF-{beta} stimulation and provide useful information towards understanding the pathogenesis of proliferative vitreoretinal diseases.« less

Using Twitter to Better Understand the Spatiotemporal Patterns of Public Sentiment: A Case Study in Massachusetts, USA.

PubMed

Cao, Xiaodong; MacNaughton, Piers; Deng, Zhengyi; Yin, Jie; Zhang, Xi; Allen, Joseph G

2018-02-02

Twitter provides a rich database of spatiotemporal information about users who broadcast their real-time opinions, sentiment, and activities. In this paper, we sought to investigate the holistic influence of land use and time period on public sentiment. A total of 880,937 tweets posted by 26,060 active users were collected across Massachusetts (MA), USA, through 31 November 2012 to 3 June 2013. The IBM Watson Alchemy API (application program interface) was employed to quantify the sentiment scores conveyed by tweets on a large scale. Then we statistically analyzed the sentiment scores across different spaces and times. A multivariate linear mixed-effects model was used to quantify the fixed effects of land use and the time period on the variations in sentiment scores, considering the clustering effect of users. The results exposed clear spatiotemporal patterns of users' sentiment. Higher sentiment scores were mainly observed in the commercial and public areas, during the noon/evening and on weekends. Our findings suggest that social media outputs can be used to better understand the spatial and temporal patterns of public happiness and well-being in cities and regions.

Using Twitter to Better Understand the Spatiotemporal Patterns of Public Sentiment: A Case Study in Massachusetts, USA

PubMed Central

MacNaughton, Piers; Deng, Zhengyi; Yin, Jie; Zhang, Xi; Allen, Joseph G.

2018-01-01

Twitter provides a rich database of spatiotemporal information about users who broadcast their real-time opinions, sentiment, and activities. In this paper, we sought to investigate the holistic influence of land use and time period on public sentiment. A total of 880,937 tweets posted by 26,060 active users were collected across Massachusetts (MA), USA, through 31 November 2012 to 3 June 2013. The IBM Watson Alchemy API (application program interface) was employed to quantify the sentiment scores conveyed by tweets on a large scale. Then we statistically analyzed the sentiment scores across different spaces and times. A multivariate linear mixed-effects model was used to quantify the fixed effects of land use and the time period on the variations in sentiment scores, considering the clustering effect of users. The results exposed clear spatiotemporal patterns of users’ sentiment. Higher sentiment scores were mainly observed in the commercial and public areas, during the noon/evening and on weekends. Our findings suggest that social media outputs can be used to better understand the spatial and temporal patterns of public happiness and well-being in cities and regions. PMID:29393869

Spatiotemporal evolution of the completeness magnitude of the Icelandic earthquake catalogue from 1991 to 2013

NASA Astrophysics Data System (ADS)

Panzera, Francesco; Mignan, Arnaud; Vogfjörð, Kristin S.

2017-07-01

In 1991, a digital seismic monitoring network was installed in Iceland with a digital seismic system and automatic operation. After 20 years of operation, we explore for the first time its nationwide performance by analysing the spatiotemporal variations of the completeness magnitude. We use the Bayesian magnitude of completeness (BMC) method that combines local completeness magnitude observations with prior information based on the density of seismic stations. Additionally, we test the impact of earthquake location uncertainties on the BMC results, by filtering the catalogue using a multivariate analysis that identifies outliers in the hypocentre error distribution. We find that the entire North-to-South active rift zone shows a relatively low magnitude of completeness Mc in the range 0.5-1.0, highlighting the ability of the Icelandic network to detect small earthquakes. This work also demonstrates the influence of earthquake location uncertainties on the spatiotemporal magnitude of completeness analysis.

Spatiotemporal property and predictability of large-scale human mobility

NASA Astrophysics Data System (ADS)

Zhang, Hai-Tao; Zhu, Tao; Fu, Dongfei; Xu, Bowen; Han, Xiao-Pu; Chen, Duxin

2018-04-01

Spatiotemporal characteristics of human mobility emerging from complexity on individual scale have been extensively studied due to the application potential on human behavior prediction and recommendation, and control of epidemic spreading. We collect and investigate a comprehensive data set of human activities on large geographical scales, including both websites browse and mobile towers visit. Numerical results show that the degree of activity decays as a power law, indicating that human behaviors are reminiscent of scale-free random walks known as Lévy flight. More significantly, this study suggests that human activities on large geographical scales have specific non-Markovian characteristics, such as a two-segment power-law distribution of dwelling time and a high possibility for prediction. Furthermore, a scale-free featured mobility model with two essential ingredients, i.e., preferential return and exploration, and a Gaussian distribution assumption on the exploration tendency parameter is proposed, which outperforms existing human mobility models under scenarios of large geographical scales.

Simultaneous Denoising, Deconvolution, and Demixing of Calcium Imaging Data

PubMed Central

Pnevmatikakis, Eftychios A.; Soudry, Daniel; Gao, Yuanjun; Machado, Timothy A.; Merel, Josh; Pfau, David; Reardon, Thomas; Mu, Yu; Lacefield, Clay; Yang, Weijian; Ahrens, Misha; Bruno, Randy; Jessell, Thomas M.; Peterka, Darcy S.; Yuste, Rafael; Paninski, Liam

2016-01-01

SUMMARY We present a modular approach for analyzing calcium imaging recordings of large neuronal ensembles. Our goal is to simultaneously identify the locations of the neurons, demix spatially overlapping components, and denoise and deconvolve the spiking activity from the slow dynamics of the calcium indicator. Our approach relies on a constrained nonnegative matrix factorization that expresses the spatiotemporal fluorescence activity as the product of a spatial matrix that encodes the spatial footprint of each neuron in the optical field and a temporal matrix that characterizes the calcium concentration of each neuron over time. This framework is combined with a novel constrained deconvolution approach that extracts estimates of neural activity from fluorescence traces, to create a spatiotemporal processing algorithm that requires minimal parameter tuning. We demonstrate the general applicability of our method by applying it to in vitro and in vivo multineuronal imaging data, whole-brain light-sheet imaging data, and dendritic imaging data. PMID:26774160

Time-specific ecological niche modeling predicts spatial dynamics of vector insects and human dengue cases.

PubMed

Peterson, A Townsend; Martínez-Campos, Carmen; Nakazawa, Yoshinori; Martínez-Meyer, Enrique

2005-09-01

Numerous human diseases-malaria, dengue, yellow fever and leishmaniasis, to name a few-are transmitted by insect vectors with brief life cycles and biting activity that varies in both space and time. Although the general geographic distributions of these epidemiologically important species are known, the spatiotemporal variation in their emergence and activity remains poorly understood. We used ecological niche modeling via a genetic algorithm to produce time-specific predictive models of monthly distributions of Aedes aegypti in Mexico in 1995. Significant predictions of monthly mosquito activity and distributions indicate that predicting spatiotemporal dynamics of disease vector species is feasible; significant coincidence with human cases of dengue indicate that these dynamics probably translate directly into transmission of dengue virus to humans. This approach provides new potential for optimizing use of resources for disease prevention and remediation via automated forecasting of disease transmission risk.

Visual representation of spatiotemporal structure

NASA Astrophysics Data System (ADS)

Schill, Kerstin; Zetzsche, Christoph; Brauer, Wilfried; Eisenkolb, A.; Musto, A.

1998-07-01

The processing and representation of motion information is addressed from an integrated perspective comprising low- level signal processing properties as well as higher-level cognitive aspects. For the low-level processing of motion information we argue that a fundamental requirement is the existence of a spatio-temporal memory. Its key feature, the provision of an orthogonal relation between external time and its internal representation, is achieved by a mapping of temporal structure into a locally distributed activity distribution accessible in parallel by higher-level processing stages. This leads to a reinterpretation of the classical concept of `iconic memory' and resolves inconsistencies on ultra-short-time processing and visual masking. The spatial-temporal memory is further investigated by experiments on the perception of spatio-temporal patterns. Results on the direction discrimination of motion paths provide evidence that information about direction and location are not processed and represented independent of each other. This suggests a unified representation on an early level, in the sense that motion information is internally available in form of a spatio-temporal compound. For the higher-level representation we have developed a formal framework for the qualitative description of courses of motion that may occur with moving objects.

On the Reliability of Individual Brain Activity Networks.

PubMed

Cassidy, Ben; Bowman, F DuBois; Rae, Caroline; Solo, Victor

2018-02-01

There is intense interest in fMRI research on whole-brain functional connectivity, and however, two fundamental issues are still unresolved: the impact of spatiotemporal data resolution (spatial parcellation and temporal sampling) and the impact of the network construction method on the reliability of functional brain networks. In particular, the impact of spatiotemporal data resolution on the resulting connectivity findings has not been sufficiently investigated. In fact, a number of studies have already observed that functional networks often give different conclusions across different parcellation scales. If the interpretations from functional networks are inconsistent across spatiotemporal scales, then the whole validity of the functional network paradigm is called into question. This paper investigates the consistency of resting state network structure when using different temporal sampling or spatial parcellation, or different methods for constructing the networks. To pursue this, we develop a novel network comparison framework based on persistent homology from a topological data analysis. We use the new network comparison tools to characterize the spatial and temporal scales under which consistent functional networks can be constructed. The methods are illustrated on Human Connectome Project data, showing that the DISCOH 2 network construction method outperforms other approaches at most data spatiotemporal resolutions.

Immortalized myogenic cells from congenital muscular dystrophy type1A patients recapitulate aberrant caspase activation in pathogenesis: a new tool for MDC1A research

PubMed Central

2013-01-01

Background Congenital muscular dystrophy Type 1A (MDC1A) is a severe, recessive disease of childhood onset that is caused by mutations in the LAMA2 gene encoding laminin-α2. Studies with both mouse models and primary cultures of human MDC1A myogenic cells suggest that aberrant activation of cell death is a significant contributor to pathogenesis in laminin-α2-deficiency. Methods To overcome the limited population doublings of primary cultures, we generated immortalized, clonal lines of human MDC1A myogenic cells via overexpression of both CDK4 and the telomerase catalytic component (human telomerase reverse transcriptase (hTERT)). Results The immortalized MDC1A myogenic cells proliferated indefinitely when cultured at low density in high serum growth medium, but retained the capacity to form multinucleate myotubes and express muscle-specific proteins when switched to low serum medium. When cultured in the absence of laminin, myotubes formed from immortalized MDC1A myoblasts, but not those formed from immortalized healthy or disease control human myoblasts, showed significantly increased activation of caspase-3. This pattern of aberrant caspase-3 activation in the immortalized cultures was similar to that found previously in primary MDC1A cultures and laminin-α2-deficient mice. Conclusions Immortalized MDC1A myogenic cells provide a new resource for studies of pathogenetic mechanisms and for screening possible therapeutic approaches in laminin-α2-deficiency. PMID:24314268

Immortalized myogenic cells from congenital muscular dystrophy type1A patients recapitulate aberrant caspase activation in pathogenesis: a new tool for MDC1A research.

PubMed

Yoon, Soonsang; Stadler, Guido; Beermann, Mary Lou; Schmidt, Eric V; Windelborn, James A; Schneiderat, Peter; Wright, Woodring E; Miller, Jeffrey Boone

2013-12-06

Congenital muscular dystrophy Type 1A (MDC1A) is a severe, recessive disease of childhood onset that is caused by mutations in the LAMA2 gene encoding laminin-α2. Studies with both mouse models and primary cultures of human MDC1A myogenic cells suggest that aberrant activation of cell death is a significant contributor to pathogenesis in laminin-α2-deficiency. To overcome the limited population doublings of primary cultures, we generated immortalized, clonal lines of human MDC1A myogenic cells via overexpression of both CDK4 and the telomerase catalytic component (human telomerase reverse transcriptase (hTERT)). The immortalized MDC1A myogenic cells proliferated indefinitely when cultured at low density in high serum growth medium, but retained the capacity to form multinucleate myotubes and express muscle-specific proteins when switched to low serum medium. When cultured in the absence of laminin, myotubes formed from immortalized MDC1A myoblasts, but not those formed from immortalized healthy or disease control human myoblasts, showed significantly increased activation of caspase-3. This pattern of aberrant caspase-3 activation in the immortalized cultures was similar to that found previously in primary MDC1A cultures and laminin-α2-deficient mice. Immortalized MDC1A myogenic cells provide a new resource for studies of pathogenetic mechanisms and for screening possible therapeutic approaches in laminin-α2-deficiency.

Short curcumin treatment modulates oxidative stress, arginase activity, aberrant crypt foci, and TGF-β1 and HES-1 transcripts in 1,2-dimethylhydrazine-colon carcinogenesis in mice.

PubMed

Bounaama, Abdelkader; Djerdjouri, Bahia; Laroche-Clary, Audrey; Le Morvan, Valérie; Robert, Jacques

2012-12-16

This study investigated the effect of short curcumin treatment, a natural antioxidant on 1,2-dimethylhydrazine (DMH)-induced aberrant crypt foci (ACF) in mice. The incidence of aberrant crypt foci (ACF) was 100%, with 54 ± 6 per colon, 10 weeks after the first DMH injection and reached 67 ± 12 per colon after 12 weeks. A high level of undifferentiated goblet cells and a weak apoptotic activity were shown in dysplastic ACF. The morphological alterations of colonic mucosa were associated to severe oxidative stress ratio with 43% increase in malondialdehyde vs. 36% decrease in GSH. DMH also increased inducible nitric synthase (iNOS) mRNA transcripts (250%), nitrites level (240%) and arginase activity (296%), leading to nitrosative stress and cell proliferation. Curcumin treatment, starting at week 10 post-DMH injection for 14 days, reduced the number of ACF (40%), iNOS expression (25%) and arginase activity (73%), and improved redox status by approximately 46%, compared to DMH-treated mice. Moreover, curcumin induced apoptosis of dysplastic ACF cells without restoring goblet cells differentiation. Interestingly, curcumin induced a parallel increase in TGF-β1 and HES-1 transcripts (42% and 26%, respectively). In conclusion, the protective effect of curcumin was driven by the reduction of arginase activity and nitrosative stress. The up regulation of TGF-β1 and HES-1 expression by curcumin suggests for the first time, a potential interplay between these signalling pathways in the chemoprotective mechanism of curcumin. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Genotoxicity assessment of magnetic iron oxide nanoparticles with different particle sizes and surface coatings

NASA Astrophysics Data System (ADS)

Liu, Yanping; Xia, Qiyue; Liu, Ying; Zhang, Shuyang; Cheng, Feng; Zhong, Zhihui; Wang, Li; Li, Hongxia; Xiao, Kai

2014-10-01

Magnetic iron oxide nanoparticles (IONPs) have been widely used for various biomedical applications such as magnetic resonance imaging and drug delivery. However, their potential toxic effects, including genotoxicity, need to be thoroughly understood. In the present study, the genotoxicity of IONPs with different particle sizes (10, 30 nm) and surface coatings (PEG, PEI) were assessed using three standard genotoxicity assays, the Salmonella typhimurium reverse mutation assay (Ames test), the in vitro mammalian chromosome aberration test, and the in vivo micronucleus assay. In the Ames test, SMG-10 (PEG coating, 10 nm) showed a positive mutagenic response in all the five test bacterial strains with and without metabolic activation, whereas SEI-10 (PEI coating, 10 nm) showed no mutagenesis in all tester strains regardless of metabolic activation. SMG-30 (PEG coating, 30 nm) was not mutagenic in the absence of metabolic activation, and became mutagenic in the presence of metabolic activation. In the chromosomal aberration test, no increase in the incidence of chromosomal aberrations was observed for all three IONPs. In the in vivo micronucleus test, there was no evidence of increased micronuclei frequencies for all three IONPs, indicating that they were not clastogenic in vivo. Taken together, our results demonstrated that IONPs with PEG coating exhibited mutagenic activity without chromosomal and clastogenic abnormalities, and smaller IONPs (SMG-10) had stronger mutagenic potential than larger ones (SMG-30); whereas, IONPs with SEI coating (SEI-10) were not genotoxic in all three standard genotoxicity assays. This suggests that the mutagenicity of IONPs depends on their particle size and surface coating.

Spatio-Temporal Characteristics of Resident Trip Based on Poi and OD Data of Float CAR in Beijing

NASA Astrophysics Data System (ADS)

Mou, N.; Li, J.; Zhang, L.; Liu, W.; Xu, Y.

2017-09-01

Due to the influence of the urban inherent regional functional distribution, the daily activities of the residents presented some spatio-temporal patterns (periodic patterns, gathering patterns, etc.). In order to further understand the spatial and temporal characteristics of urban residents, this paper research takes the taxi trajectory data of Beijing as a sample data and studies the spatio-temporal characteristics of the residents' activities on the weekdays. At first, according to the characteristics of the taxi trajectory data distributed along the road network, it takes the Voronoi generated by the road nodes as the research unit. This paper proposes a hybrid clustering method - based on grid density, which is used to cluster the OD (origin and destination) data of taxi at different times. Then combining with the POI data of Beijing, this research calculated the density of the POI data in the clustering results, and analyzed the relationship between the activities of residents in different periods and the functional types of the region. The final results showed that the residents were mainly commuting on weekdays. And it found that the distribution of travel density showed a concentric circle of the characteristics, focusing on residential areas and work areas. The results of cluster analysis and POI analysis showed that the residents' travel had experienced the process of "spatial relative dispersion - spatial aggregation - spatial relative dispersion" in one day.

NeuroMap: A Spline-Based Interactive Open-Source Software for Spatiotemporal Mapping of 2D and 3D MEA Data

PubMed Central

Abdoun, Oussama; Joucla, Sébastien; Mazzocco, Claire; Yvert, Blaise

2010-01-01

A major characteristic of neural networks is the complexity of their organization at various spatial scales, from microscopic local circuits to macroscopic brain-scale areas. Understanding how neural information is processed thus entails the ability to study them at multiple scales simultaneously. This is made possible using microelectrodes array (MEA) technology. Indeed, high-density MEAs provide large-scale coverage (several square millimeters) of whole neural structures combined with microscopic resolution (about 50 μm) of unit activity. Yet, current options for spatiotemporal representation of MEA-collected data remain limited. Here we present NeuroMap, a new interactive Matlab-based software for spatiotemporal mapping of MEA data. NeuroMap uses thin plate spline interpolation, which provides several assets with respect to conventional mapping methods used currently. First, any MEA design can be considered, including 2D or 3D, regular or irregular, arrangements of electrodes. Second, spline interpolation allows the estimation of activity across the tissue with local extrema not necessarily at recording sites. Finally, this interpolation approach provides a straightforward analytical estimation of the spatial Laplacian for better current sources localization. In this software, coregistration of 2D MEA data on the anatomy of the neural tissue is made possible by fine matching of anatomical data with electrode positions using rigid-deformation-based correction of anatomical pictures. Overall, NeuroMap provides substantial material for detailed spatiotemporal analysis of MEA data. The package is distributed under GNU General Public License and available at http://sites.google.com/site/neuromapsoftware. PMID:21344013

NeuroMap: A Spline-Based Interactive Open-Source Software for Spatiotemporal Mapping of 2D and 3D MEA Data.

PubMed

Abdoun, Oussama; Joucla, Sébastien; Mazzocco, Claire; Yvert, Blaise

2011-01-01

A major characteristic of neural networks is the complexity of their organization at various spatial scales, from microscopic local circuits to macroscopic brain-scale areas. Understanding how neural information is processed thus entails the ability to study them at multiple scales simultaneously. This is made possible using microelectrodes array (MEA) technology. Indeed, high-density MEAs provide large-scale coverage (several square millimeters) of whole neural structures combined with microscopic resolution (about 50 μm) of unit activity. Yet, current options for spatiotemporal representation of MEA-collected data remain limited. Here we present NeuroMap, a new interactive Matlab-based software for spatiotemporal mapping of MEA data. NeuroMap uses thin plate spline interpolation, which provides several assets with respect to conventional mapping methods used currently. First, any MEA design can be considered, including 2D or 3D, regular or irregular, arrangements of electrodes. Second, spline interpolation allows the estimation of activity across the tissue with local extrema not necessarily at recording sites. Finally, this interpolation approach provides a straightforward analytical estimation of the spatial Laplacian for better current sources localization. In this software, coregistration of 2D MEA data on the anatomy of the neural tissue is made possible by fine matching of anatomical data with electrode positions using rigid-deformation-based correction of anatomical pictures. Overall, NeuroMap provides substantial material for detailed spatiotemporal analysis of MEA data. The package is distributed under GNU General Public License and available at http://sites.google.com/site/neuromapsoftware.

Stress Sensitivity, Aberrant Salience, and Threat Anticipation in Early Psychosis: An Experience Sampling Study.

PubMed

Reininghaus, Ulrich; Kempton, Matthew J; Valmaggia, Lucia; Craig, Tom K J; Garety, Philippa; Onyejiaka, Adanna; Gayer-Anderson, Charlotte; So, Suzanne H; Hubbard, Kathryn; Beards, Stephanie; Dazzan, Paola; Pariante, Carmine; Mondelli, Valeria; Fisher, Helen L; Mills, John G; Viechtbauer, Wolfgang; McGuire, Philip; van Os, Jim; Murray, Robin M; Wykes, Til; Myin-Germeys, Inez; Morgan, Craig

2016-05-01

While contemporary models of psychosis have proposed a number of putative psychological mechanisms, how these impact on individuals to increase intensity of psychotic experiences in real life, outside the research laboratory, remains unclear. We aimed to investigate whether elevated stress sensitivity, experiences of aberrant novelty and salience, and enhanced anticipation of threat contribute to the development of psychotic experiences in daily life. We used the experience sampling method (ESM) to assess stress, negative affect, aberrant salience, threat anticipation, and psychotic experiences in 51 individuals with first-episode psychosis (FEP), 46 individuals with an at-risk mental state (ARMS) for psychosis, and 53 controls with no personal or family history of psychosis. Linear mixed models were used to account for the multilevel structure of ESM data. In all 3 groups, elevated stress sensitivity, aberrant salience, and enhanced threat anticipation were associated with an increased intensity of psychotic experiences. However, elevated sensitivity to minor stressful events (χ(2)= 6.3,P= 0.044), activities (χ(2)= 6.7,P= 0.036), and areas (χ(2)= 9.4,P= 0.009) and enhanced threat anticipation (χ(2)= 9.3,P= 0.009) were associated with more intense psychotic experiences in FEP individuals than controls. Sensitivity to outsider status (χ(2)= 5.7,P= 0.058) and aberrantly salient experiences (χ(2)= 12.3,P= 0.002) were more strongly associated with psychotic experiences in ARMS individuals than controls. Our findings suggest that stress sensitivity, aberrant salience, and threat anticipation are important psychological processes in the development of psychotic experiences in daily life in the early stages of the disorder. © The Author 2016. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.

Stress Sensitivity, Aberrant Salience, and Threat Anticipation in Early Psychosis: An Experience Sampling Study

PubMed Central

Reininghaus, Ulrich; Kempton, Matthew J.; Valmaggia, Lucia; Craig, Tom K. J.; Garety, Philippa; Onyejiaka, Adanna; Gayer-Anderson, Charlotte; So, Suzanne H.; Hubbard, Kathryn; Beards, Stephanie; Dazzan, Paola; Pariante, Carmine; Mondelli, Valeria; Fisher, Helen L.; Mills, John G.; Viechtbauer, Wolfgang; McGuire, Philip; van Os, Jim; Murray, Robin M.; Wykes, Til; Myin-Germeys, Inez; Morgan, Craig

2016-01-01

While contemporary models of psychosis have proposed a number of putative psychological mechanisms, how these impact on individuals to increase intensity of psychotic experiences in real life, outside the research laboratory, remains unclear. We aimed to investigate whether elevated stress sensitivity, experiences of aberrant novelty and salience, and enhanced anticipation of threat contribute to the development of psychotic experiences in daily life. We used the experience sampling method (ESM) to assess stress, negative affect, aberrant salience, threat anticipation, and psychotic experiences in 51 individuals with first-episode psychosis (FEP), 46 individuals with an at-risk mental state (ARMS) for psychosis, and 53 controls with no personal or family history of psychosis. Linear mixed models were used to account for the multilevel structure of ESM data. In all 3 groups, elevated stress sensitivity, aberrant salience, and enhanced threat anticipation were associated with an increased intensity of psychotic experiences. However, elevated sensitivity to minor stressful events (χ2 = 6.3, P = 0.044), activities (χ2 = 6.7, P = 0.036), and areas (χ2 = 9.4, P = 0.009) and enhanced threat anticipation (χ2 = 9.3, P = 0.009) were associated with more intense psychotic experiences in FEP individuals than controls. Sensitivity to outsider status (χ2 = 5.7, P = 0.058) and aberrantly salient experiences (χ2 = 12.3, P = 0.002) were more strongly associated with psychotic experiences in ARMS individuals than controls. Our findings suggest that stress sensitivity, aberrant salience, and threat anticipation are important psychological processes in the development of psychotic experiences in daily life in the early stages of the disorder. PMID:26834027

The transcription factor Grainy head primes epithelial enhancers for spatiotemporal activation by displacing nucleosomes.

PubMed

Jacobs, Jelle; Atkins, Mardelle; Davie, Kristofer; Imrichova, Hana; Romanelli, Lucia; Christiaens, Valerie; Hulselmans, Gert; Potier, Delphine; Wouters, Jasper; Taskiran, Ibrahim I; Paciello, Giulia; González-Blas, Carmen B; Koldere, Duygu; Aibar, Sara; Halder, Georg; Aerts, Stein

2018-06-04

Transcriptional enhancers function as docking platforms for combinations of transcription factors (TFs) to control gene expression. How enhancer sequences determine nucleosome occupancy, TF recruitment and transcriptional activation in vivo remains unclear. Using ATAC-seq across a panel of Drosophila inbred strains, we found that SNPs affecting binding sites of the TF Grainy head (Grh) causally determine the accessibility of epithelial enhancers. We show that deletion and ectopic expression of Grh cause loss and gain of DNA accessibility, respectively. However, although Grh binding is necessary for enhancer accessibility, it is insufficient to activate enhancers. Finally, we show that human Grh homologs-GRHL1, GRHL2 and GRHL3-function similarly. We conclude that Grh binding is necessary and sufficient for the opening of epithelial enhancers but not for their activation. Our data support a model positing that complex spatiotemporal expression patterns are controlled by regulatory hierarchies in which pioneer factors, such as Grh, establish tissue-specific accessible chromatin landscapes upon which other factors can act.

Hand gesture recognition in confined spaces with partial observability and occultation constraints

NASA Astrophysics Data System (ADS)

Shirkhodaie, Amir; Chan, Alex; Hu, Shuowen

2016-05-01

Human activity detection and recognition capabilities have broad applications for military and homeland security. These tasks are very complicated, however, especially when multiple persons are performing concurrent activities in confined spaces that impose significant obstruction, occultation, and observability uncertainty. In this paper, our primary contribution is to present a dedicated taxonomy and kinematic ontology that are developed for in-vehicle group human activities (IVGA). Secondly, we describe a set of hand-observable patterns that represents certain IVGA examples. Thirdly, we propose two classifiers for hand gesture recognition and compare their performance individually and jointly. Finally, we present a variant of Hidden Markov Model for Bayesian tracking, recognition, and annotation of hand motions, which enables spatiotemporal inference to human group activity perception and understanding. To validate our approach, synthetic (graphical data from virtual environment) and real physical environment video imagery are employed to verify the performance of these hand gesture classifiers, while measuring their efficiency and effectiveness based on the proposed Hidden Markov Model for tracking and interpreting dynamic spatiotemporal IVGA scenarios.

Fire-climate interactions in the American West since 1400 CE

NASA Astrophysics Data System (ADS)

Trouet, Valerie; Taylor, Alan H.; Wahl, Eugene R.; Skinner, Carl N.; Stephens, Scott L.

2010-02-01

Despite a strong anthropogenic fingerprint on 20th Century wildland fire activity in the American West, climate remains a main driver. A better understanding of the spatio-temporal variability in fire-climate interactions is therefore crucial for fire management. Here, we present annually resolved, tree-ring based fire records for four regions in the American West that extend back to 1400 CE. In all regions, years with high fire activity were characterized by widespread yet regionally distinct summer droughts. Overall fire activity was high in late Medieval times, when much of the American West was affected by mega-droughts. A distinct decline in fire activity in the late 16th Century corresponds with anomalously low temperatures during the Little Ice Age and a decline in Native American fire use. The high spatiotemporal resolution of our fire record discloses a time-frequency dependent climatic influence on wildfire regimes in the American West that needs to be accounted for in fire models.

Methods, caveats and the future of large-scale microelectrode recordings in the non-human primate

PubMed Central

Dotson, Nicholas M.; Goodell, Baldwin; Salazar, Rodrigo F.; Hoffman, Steven J.; Gray, Charles M.

2015-01-01

Cognitive processes play out on massive brain-wide networks, which produce widely distributed patterns of activity. Capturing these activity patterns requires tools that are able to simultaneously measure activity from many distributed sites with high spatiotemporal resolution. Unfortunately, current techniques with adequate coverage do not provide the requisite spatiotemporal resolution. Large-scale microelectrode recording devices, with dozens to hundreds of microelectrodes capable of simultaneously recording from nearly as many cortical and subcortical areas, provide a potential way to minimize these tradeoffs. However, placing hundreds of microelectrodes into a behaving animal is a highly risky and technically challenging endeavor that has only been pursued by a few groups. Recording activity from multiple electrodes simultaneously also introduces several statistical and conceptual dilemmas, such as the multiple comparisons problem and the uncontrolled stimulus response problem. In this perspective article, we discuss some of the techniques that we, and others, have developed for collecting and analyzing large-scale data sets, and address the future of this emerging field. PMID:26578906

High-resolution optical control of spatiotemporal neuronal activity patterns in zebrafish using a digital micromirror device.

PubMed

Zhu, Peixin; Fajardo, Otto; Shum, Jennifer; Zhang Schärer, Yan-Ping; Friedrich, Rainer W

2012-06-28

Optogenetic approaches allow the manipulation of neuronal activity patterns in space and time by light, particularly in small animals such as zebrafish. However, most techniques cannot control neuronal activity independently at different locations. Here we describe equipment and provide a protocol for single-photon patterned optical stimulation of neurons using a digital micromirror device (DMD). This method can create arbitrary spatiotemporal light patterns with spatial and temporal resolutions in the micrometer and submillisecond range, respectively. Different options to integrate a DMD into a multiphoton microscope are presented and compared. We also describe an ex vivo preparation of the adult zebrafish head that greatly facilitates optogenetic and other experiments. After assembly, the initial alignment takes about one day and the zebrafish preparation takes <30 min. The method has previously been used to activate channelrhodopsin-2 and manipulate oscillatory synchrony among spatially distributed neurons in the zebrafish olfactory bulb. It can be adapted easily to a wide range of other species, optogenetic probes and scientific applications.

Composite catalyst surfaces: Effect of inert and active heterogeneities on pattern formation

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

Baer, M.; Bangia, A.K.; Kevrekidis, I.G.

1996-12-05

Spatiotemporal dynamics in reaction-diffusion systems can be altered through the properties (reactivity, diffusivity) of the medium in which they occur. We construct active heterogeneous media (composite catalytic surfaces with inert as well as active illusions) using microelectronics fabrication techniques and study the spatiotemporal dynamics of heterogeneous catalytic reactions on these catalysts. In parallel, we perform simulations as well as numerical stability and bifurcation analysis of these patterns using mechanistic models. At the limit of large heterogeneity `grain size` (compared to the wavelength of spontaneously arising structures) the interaction patterns with inert or active boundaries dominates (e.g., pinning, transmission, and boundarymore » breakup of spirals, interaction of pulses with corners, `pacemaker` effects). At the opposite limit of very small or very finely distributed heterogeneity, effective behavior is observed (slight modulation of pulses, nearly uniform oscillations, effective spirals). Some representative studies of transitions between the two limits are presented. 48 refs., 11 figs.« less

Biophysics of object segmentation in a collision-detecting neuron

PubMed Central

Dewell, Richard Burkett

2018-01-01

Collision avoidance is critical for survival, including in humans, and many species possess visual neurons exquisitely sensitive to objects approaching on a collision course. Here, we demonstrate that a collision-detecting neuron can detect the spatial coherence of a simulated impending object, thereby carrying out a computation akin to object segmentation critical for proper escape behavior. At the cellular level, object segmentation relies on a precise selection of the spatiotemporal pattern of synaptic inputs by dendritic membrane potential-activated channels. One channel type linked to dendritic computations in many neural systems, the hyperpolarization-activated cation channel, HCN, plays a central role in this computation. Pharmacological block of HCN channels abolishes the neuron's spatial selectivity and impairs the generation of visually guided escape behaviors, making it directly relevant to survival. Additionally, our results suggest that the interaction of HCN and inactivating K+ channels within active dendrites produces neuronal and behavioral object specificity by discriminating between complex spatiotemporal synaptic activation patterns. PMID:29667927

Extreme brain events: Higher-order statistics of brain resting activity and its relation with structural connectivity

NASA Astrophysics Data System (ADS)

Amor, T. A.; Russo, R.; Diez, I.; Bharath, P.; Zirovich, M.; Stramaglia, S.; Cortes, J. M.; de Arcangelis, L.; Chialvo, D. R.

2015-09-01

The brain exhibits a wide variety of spatiotemporal patterns of neuronal activity recorded using functional magnetic resonance imaging as the so-called blood-oxygenated-level-dependent (BOLD) signal. An active area of work includes efforts to best describe the plethora of these patterns evolving continuously in the brain. Here we explore the third-moment statistics of the brain BOLD signals in the resting state as a proxy to capture extreme BOLD events. We find that the brain signal exhibits typically nonzero skewness, with positive values for cortical regions and negative values for subcortical regions. Furthermore, the combined analysis of structural and functional connectivity demonstrates that relatively more connected regions exhibit activity with high negative skewness. Overall, these results highlight the relevance of recent results emphasizing that the spatiotemporal location of the relatively large-amplitude events in the BOLD time series contains relevant information to reproduce a number of features of the brain dynamics during resting state in health and disease.

Construction of special eye models for investigation of chromatic and higher-order aberrations of eyes.

PubMed

Zhai, Yi; Wang, Yan; Wang, Zhaoqi; Liu, Yongji; Zhang, Lin; He, Yuanqing; Chang, Shengjiang

2014-01-01

An achromatic element eliminating only longitudinal chromatic aberration (LCA) while maintaining transverse chromatic aberration (TCA) is established for the eye model, which involves the angle formed by the visual and optical axis. To investigate the impacts of higher-order aberrations on vision, the actual data of higher-order aberrations of human eyes with three typical levels are introduced into the eye model along visual axis. Moreover, three kinds of individual eye models are established to investigate the impacts of higher-order aberrations, chromatic aberration (LCA+TCA), LCA and TCA on vision under the photopic condition, respectively. Results show that for most human eyes, the impact of chromatic aberration on vision is much stronger than that of higher-order aberrations, and the impact of LCA in chromatic aberration dominates. The impact of TCA is approximately equal to that of normal level higher-order aberrations and it can be ignored when LCA exists.

Sixth-order wave aberration theory of ultrawide-angle optical systems.

PubMed

Lu, Lijun; Cao, Yiqing

2017-10-20

In this paper, we develop sixth-order wave aberration theory of ultrawide-angle optical systems like fisheye lenses. Based on the concept and approach to develop wave aberration theory of plane-symmetric optical systems, we first derive the sixth-order intrinsic wave aberrations and the fifth-order ray aberrations; second, we present a method to calculate the pupil aberration of such kind of optical systems to develop the extrinsic aberrations; third, the relation of aperture-ray coordinates between adjacent optical surfaces is fitted with the second-order polynomial to improve the calculation accuracy of the wave aberrations of a fisheye lens with a large acceptance aperture. Finally, the resultant aberration expressions are applied to calculate the aberrations of two design examples of fisheye lenses; the calculation results are compared with the ray-tracing ones with Zemax software to validate the aberration expressions.

MAGNETIC LIQUID DEFORMABLE MIRRORS FOR ASTRONOMICAL APPLICATIONS: ACTIVE CORRECTION OF OPTICAL ABERRATIONS FROM LOWER-GRADE OPTICS AND SUPPORT SYSTEM

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

Borra, E. F., E-mail: borra@phy.ulaval.ca

2012-08-01

Deformable mirrors are increasingly used in astronomy. However, they still are limited in stroke for active correction of high-amplitude optical aberrations. Magnetic liquid deformable mirrors (MLDMs) are a new technology that has the advantages of high-amplitude deformations and low costs. In this paper, we demonstrate extremely high strokes and interactuator strokes achievable by MLDMs which can be used in astronomical instrumentation. In particular, we consider the use of such a mirror to suggest an interesting application for the next generation of large telescopes. We present a prototype 91 actuator deformable mirror made of a magnetic liquid (ferrofluid). This mirror usesmore » a technique that linearizes the response of such mirrors by superimposing a large and uniform magnetic field on the magnetic field produced by an array of small coils. We discuss experimental results that illustrate the performance of MLDMs. A most interesting application of MLDMs comes from the fact they could be used to correct the aberrations of large and lower optical quality primary mirrors held by simple support systems. We estimate basic parameters of the needed MLDMs, obtaining reasonable values.« less

Gastric Carcinogenesis and Underlying Molecular Mechanisms: Helicobacter pylori and Novel Targeted Therapy

PubMed Central

Nishizawa, Toshihiro

2015-01-01

The oxygen-derived free radicals that are released from activated neutrophils are one of the cytotoxic factors of Helicobacter pylori-induced gastric mucosal injury. Increased cytidine deaminase activity in H. pylori-infected gastric tissues promotes the accumulation of various mutations and might promote gastric carcinogenesis. Cytotoxin-associated gene A (CagA) is delivered into gastric epithelial cells via bacterial type IV secretion system, and it causes inflammation and activation of oncogenic pathways. H. pylori infection induces epigenetic transformations, such as aberrant promoter methylation in tumor-suppressor genes. Aberrant expression of microRNAs is also reportedly linked to gastric tumorogenesis. Moreover, recent advances in molecular targeting therapies provided a new interesting weapon to treat advanced gastric cancer through anti-human epidermal growth factor receptor 2 (HER-2) therapies. This updated review article highlights possible mechanisms of gastric carcinogenesis including H. pylori-associated factors. PMID:25945346

Highly efficient intracellular transduction in three-dimensional gradients for programming cell fate.

PubMed

Eltaher, Hoda M; Yang, Jing; Shakesheff, Kevin M; Dixon, James E

2016-09-01

Fundamental behaviour such as cell fate, growth and death are mediated through the control of key genetic transcriptional regulators. These regulators are activated or repressed by the integration of multiple signalling molecules in spatio-temporal gradients. Engineering these gradients is complex but considered key in controlling tissue formation in regenerative medicine approaches. Direct programming of cells using exogenously delivered transcription factors can by-pass growth factor complexity but there is still a requirement to deliver such activity spatio-temporally. We previously developed a technology termed GAG-binding enhanced transduction (GET) to efficiently deliver a variety of cargoes intracellularly using GAG-binding domains to promote cell targeting, and cell penetrating peptides (CPPs) to allow cell entry. Herein we demonstrate that GET can be used in a three dimensional (3D) hydrogel matrix to produce gradients of intracellular transduction of mammalian cells. Using a compartmentalised diffusion model with a source-gel-sink (So-G-Si) assembly, we created gradients of reporter proteins (mRFP1-tagged) and a transcription factor (TF, myogenic master regulator MyoD) and showed that GET can be used to deliver molecules into cells spatio-temporally by monitoring intracellular transduction and gene expression programming as a function of location and time. The ability to spatio-temporally control the intracellular delivery of functional proteins will allow the establishment of gradients of cell programming in hydrogels and approaches to direct cellular behaviour for many regenerative medicine applications. Regenerative medicine aims to reform functional biological tissues by controlling cell behaviour. Growth factors (GFs) are soluble cues presented to cells in spatio-temporal gradients and play important roles programming cell fate and gene expression. The efficient transduction of cells by GET (Glycosaminoglycan-enhanced transducing)-tagged transcription factors (TFs) can be used to by-pass GF-stimulation and directly program cells. For the first time we demonstrate diffusion of GET proteins generate stable protein transduction gradients. We demonstrated the feasibility of creating spatio-temporal gradients of GET-MyoD and show differential programing of myogenic differentiation. We believe that GET could provide a powerful tool to program cell behaviour using gradients of recombinant proteins that allow tissue generation directly by programming gene expression with TFs. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

A Cdk5 inhibitory peptide reduces tau hyperphosphorylation and apoptosis in neurons

PubMed Central

Zheng, Ya-Li; Kesavapany, Sashi; Gravell, Maneth; Hamilton, Rebecca S; Schubert, Manfred; Amin, Niranjana; Albers, Wayne; Grant, Philip; Pant, Harish C

2005-01-01

The extracellular aggregation of amyloid β (Aβ) peptides and the intracellular hyperphosphorylation of tau at specific epitopes are pathological hallmarks of neurodegenerative diseases such as Alzheimer's disease (AD). Cdk5 phosphorylates tau at AD-specific phospho-epitopes when it associates with p25. p25 is a truncated activator, which is produced from the physiological Cdk5 activator p35 upon exposure to Aβ peptides. We show that neuronal infections with Cdk5 inhibitory peptide (CIP) selectively inhibit p25/Cdk5 activity and suppress the aberrant tau phosphorylation in cortical neurons. Furthermore, Aβ1−42-induced apoptosis of these cortical neurons was also reduced by coinfection with CIP. Of particular importance is our finding that CIP did not inhibit endogenous or transfected p35/Cdk5 activity, nor did it inhibit the other cyclin-dependent kinases such as Cdc2, Cdk2, Cdk4 and Cdk6. These results, therefore, provide a strategy to address, and possibly ameliorate, the pathology of neurodegenerative diseases that may be a consequence of aberrant p25 activation of Cdk5, without affecting ‘normal' Cdk5 activity. PMID:15592431

Surgical treatment for the aberrant internal carotid artery in the middle ear with pulsatile tinnitus.

PubMed

Honkura, Yohei; Hidaka, Hiroshi; Ohta, Jun; Gorai, Shigeki; Katori, Yukio; Kobayashi, Toshimitsu

2014-04-01

Many previous reports have indicated that pulsatile tinnitus caused by an aberrant internal carotid artery (ICA) should not be treated surgically because of the risk of infection or aneurysm formation. We herein describe a case of aberrant ICA treated by middle ear surgery for which we introduced a novel approach. An 84-year-old man was presented with a one-year history of tinnitus in his right ear. Otoscopic examination demonstrated a whitish mass in the antero-inferior quadrant of the tympanic membrane associated with rhythmic pulsation. Images obtained by CT, MRI and MRA revealed protrusion of the ICA into the tympanic cavity, making contact with the tympanic membrane. Surgery to separate the tympanic membrane from the ICA was performed in order to relieve the pulsatile tinnitus. After the operation, the patient's aural activity was preserved and the tinnitus did not recur within a follow-up period of one year. In the present case, delicate middle ear surgery was effective for relief of the tinnitus. When treating patients with aberrant IAC showing features similar to the present case, the surgical approach we have described is worth attempting. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Epigenome Aberrations: Emerging Driving Factors of the Clear Cell Renal Cell Carcinoma

PubMed Central

Mehdi, Ali; Riazalhosseini, Yasser

2017-01-01

Clear cell renal cell carcinoma (ccRCC), the most common form of Kidney cancer, is characterized by frequent mutations of the von Hippel-Lindau (VHL) tumor suppressor gene in ~85% of sporadic cases. Loss of pVHL function affects multiple cellular processes, among which the activation of hypoxia inducible factor (HIF) pathway is the best-known function. Constitutive activation of HIF signaling in turn activates hundreds of genes involved in numerous oncogenic pathways, which contribute to the development or progression of ccRCC. Although VHL mutations are considered as drivers of ccRCC, they are not sufficient to cause the disease. Recent genome-wide sequencing studies of ccRCC have revealed that mutations of genes coding for epigenome modifiers and chromatin remodelers, including PBRM1, SETD2 and BAP1, are the most common somatic genetic abnormalities after VHL mutations in these tumors. Moreover, recent research has shed light on the extent of abnormal epigenome alterations in ccRCC tumors, including aberrant DNA methylation patterns, abnormal histone modifications and deregulated expression of non-coding RNAs. In this review, we discuss the epigenetic modifiers that are commonly mutated in ccRCC, and our growing knowledge of the cellular processes that are impacted by them. Furthermore, we explore new avenues for developing therapeutic approaches based on our knowledge of epigenome aberrations of ccRCC. PMID:28812986

Epigenome Aberrations: Emerging Driving Factors of the Clear Cell Renal Cell Carcinoma.

PubMed

Mehdi, Ali; Riazalhosseini, Yasser

2017-08-16

Clear cell renal cell carcinoma (ccRCC), the most common form of Kidney cancer, is characterized by frequent mutations of the von Hippel-Lindau ( VHL ) tumor suppressor gene in ~85% of sporadic cases. Loss of pVHL function affects multiple cellular processes, among which the activation of hypoxia inducible factor (HIF) pathway is the best-known function. Constitutive activation of HIF signaling in turn activates hundreds of genes involved in numerous oncogenic pathways, which contribute to the development or progression of ccRCC. Although VHL mutations are considered as drivers of ccRCC, they are not sufficient to cause the disease. Recent genome-wide sequencing studies of ccRCC have revealed that mutations of genes coding for epigenome modifiers and chromatin remodelers, including PBRM1 , SETD2 and BAP1 , are the most common somatic genetic abnormalities after VHL mutations in these tumors. Moreover, recent research has shed light on the extent of abnormal epigenome alterations in ccRCC tumors, including aberrant DNA methylation patterns, abnormal histone modifications and deregulated expression of non-coding RNAs. In this review, we discuss the epigenetic modifiers that are commonly mutated in ccRCC, and our growing knowledge of the cellular processes that are impacted by them. Furthermore, we explore new avenues for developing therapeutic approaches based on our knowledge of epigenome aberrations of ccRCC.

Epstein-Barr virus infection induces aberrant TLR activation pathway and fibroblast-myofibroblast conversion in scleroderma.

PubMed

Farina, Antonella; Cirone, Mara; York, Michael; Lenna, Stefania; Padilla, Cristina; Mclaughlin, Sarah; Faggioni, Alberto; Lafyatis, Robert; Trojanowska, Maria; Farina, Giuseppina A

2014-04-01

Scleroderma (SSc) is a complex and heterogeneous connective tissue disease mainly characterized by autoimmunity, vascular damage, and fibrosis that mostly involve the skin and lungs. Epstein-Barr virus (EBV) is a lymphotropic γ-herpesvirus that has co-evolved with human species, infecting >95% of the adult population worldwide, and has been a leading candidate in triggering several autoimmune diseases. Here we show that EBV establishes infection in the majority of fibroblasts and endothelial cells in the skin of SSc patients, characterized by the expression of the EBV noncoding small RNAs (EBERs) and the increased expression of immediate-early lytic and latency mRNAs and proteins. We report that EBV is able to persistently infect human SSc fibroblasts in vitro, inducing an aberrant innate immune response in infected cells. EBV-Toll-like receptor (TLR) aberrant activation induces the expression of selected IFN-regulatory factors (IRFs), IFN-stimulated genes (ISGs), transforming growth factor-β1 (TGFβ1), and several markers of fibroblast activation, such as smooth muscle actin and Endothelin-1, and all of these genes play a key role in determining the profibrotic phenotype in SSc fibroblasts. These findings imply that EBV infection occurring in mesenchymal, endothelial, and immune cells of SSc patients may underlie the main pathological features of SSc including autoimmunity, vasculopathy, and fibrosis, and provide a unified disease mechanism represented by EBV reactivation.

Multi-Spatiotemporal Patterns of Residential Burglary Crimes in Chicago: 2006-2016

NASA Astrophysics Data System (ADS)

Luo, J.

2017-10-01

This research attempts to explore the patterns of burglary crimes at multi-spatiotemporal scales in Chicago between 2006 and 2016. Two spatial scales are investigated that are census block and police beat area. At each spatial scale, three temporal scales are integrated to make spatiotemporal slices: hourly scale with two-hour time step from 12:00am to the end of the day; daily scale with one-day step from Sunday to Saturday within a week; monthly scale with one-month step from January to December. A total of six types of spatiotemporal slices will be created as the base for the analysis. Burglary crimes are spatiotemporally aggregated to spatiotemporal slices based on where and when they occurred. For each type of spatiotemporal slices with burglary occurrences integrated, spatiotemporal neighborhood will be defined and managed in a spatiotemporal matrix. Hot-spot analysis will identify spatiotemporal clusters of each type of spatiotemporal slices. Spatiotemporal trend analysis is conducted to indicate how the clusters shift in space and time. The analysis results will provide helpful information for better target policing and crime prevention policy such as police patrol scheduling regarding times and places covered.

Anterior Corneal, Posterior Corneal, and Lenticular Contributions to Ocular Aberrations.

PubMed

Atchison, David A; Suheimat, Marwan; Mathur, Ankit; Lister, Lucas J; Rozema, Jos

2016-10-01

To determine the corneal surfaces and lens contributions to ocular aberrations. There were 61 healthy participants with ages ranging from 20 to 55 years and refractions -8.25 diopters (D) to +3.25 D. Anterior and posterior corneal topographies were obtained with an Oculus Pentacam, and ocular aberrations were obtained with an iTrace aberrometer. Raytracing through models of corneas provided total corneal and surface component aberrations for 5-mm-diameter pupils. Lenticular contributions were given as differences between ocular and corneal aberrations. Theoretical raytracing investigated influence of object distance on aberrations. Apart from defocus, the highest aberration coefficients were horizontal astigmatism, horizontal coma, and spherical aberration. Most correlations between lenticular and ocular parameters were positive and significant, with compensation of total corneal aberrations by lenticular aberrations for 5/12 coefficients. Anterior corneal aberrations were approximately three times higher than posterior corneal aberrations and usually had opposite signs. Corneal topographic centers were displaced from aberrometer pupil centers by 0.32 ± 0.19 mm nasally and 0.02 ± 0.16 mm inferiorly; disregarding corneal decentration relative to pupil center was significant for oblique astigmatism, horizontal coma, and horizontal trefoil. An object at infinity, rather than at the image in the anterior cornea, gave incorrect aberration estimates of the posterior cornea. Corneal and lenticular aberration magnitudes are similar, and aberrations of the anterior corneal surface are approximately three times those of the posterior surface. Corneal decentration relative to pupil center has significant effects on oblique astigmatism, horizontal coma, and horizontal trefoil. When estimating component aberrations, it is important to use correct object/image conjugates and heights at surfaces.

NF-κB Signalling in Glioblastoma

PubMed Central

Soubannier, Vincent; Stifani, Stefano

2017-01-01

Nuclear factor-κB (NF-κB) is a transcription factor regulating a wide array of genes mediating numerous cellular processes such as proliferation, differentiation, motility and survival, to name a few. Aberrant activation of NF-κB is a frequent event in numerous cancers, including glioblastoma, the most common and lethal form of brain tumours of glial cell origin (collectively termed gliomas). Glioblastoma is characterized by high cellular heterogeneity, resistance to therapy and almost inevitable recurrence after surgery and treatment. NF-κB is aberrantly activated in response to a variety of stimuli in glioblastoma, where its activity has been implicated in processes ranging from maintenance of cancer stem-like cells, stimulation of cancer cell invasion, promotion of mesenchymal identity, and resistance to radiotherapy. This review examines the mechanisms of NF-κB activation in glioblastoma, the involvement of NF-κB in several mechanisms underlying glioblastoma propagation, and discusses some of the important questions of future research into the roles of NF-κB in glioblastoma. PMID:28598356

Double-aberration corrected TEM/STEM of solid acid nanocatalysts in the development of pharmaceutical NSAIDS

NASA Astrophysics Data System (ADS)

Yoshida, K.; Shiju, N.; Brown, R.; Wright, I.; Boyes, E. D.; Gai, P. L.

2012-07-01

We report nanostructural and physico-chemical studies in the development of an efficient low temperature heterogeneous catalytic process for nonsteroidal anti-inflammatory drugs (NSAIDS) such as N-acetyl-p-aminophenol (paracetamol or acetaminophen) on tungstated zirconia nanocatalysts. Using a double-aberration corrected TEM/STEM, modified in-house for in-situ studies at the sub-Angstrom level, we directly observed in real-time, the dynamic precursor transformation to the active catalyst. We quantified the observations with catalytic activity studies for the NSAIDS. The studies have provided the direct evidence for single tungsten promoter atoms and surface WOx species of <= 0.35 nm, with nanoclusters of WOx (0.6 to 1nm), located at grain boundaries on the surface of the zirconia nanoparticles. The correlation between the nanostructure and catalytic activity indicates that the species create Brønsted acid sites highly active for the low temperature process. The results open up opportunities for developing green heterogeneous methods for pharmaceuticals.

Assessing global vegetation activity using spatio-temporal Bayesian modelling

NASA Astrophysics Data System (ADS)

Mulder, Vera L.; van Eck, Christel M.; Friedlingstein, Pierre; Regnier, Pierre A. G.

2016-04-01

This work demonstrates the potential of modelling vegetation activity using a hierarchical Bayesian spatio-temporal model. This approach allows modelling changes in vegetation and climate simultaneous in space and time. Changes of vegetation activity such as phenology are modelled as a dynamic process depending on climate variability in both space and time. Additionally, differences in observed vegetation status can be contributed to other abiotic ecosystem properties, e.g. soil and terrain properties. Although these properties do not change in time, they do change in space and may provide valuable information in addition to the climate dynamics. The spatio-temporal Bayesian models were calibrated at a regional scale because the local trends in space and time can be better captured by the model. The regional subsets were defined according to the SREX segmentation, as defined by the IPCC. Each region is considered being relatively homogeneous in terms of large-scale climate and biomes, still capturing small-scale (grid-cell level) variability. Modelling within these regions is hence expected to be less uncertain due to the absence of these large-scale patterns, compared to a global approach. This overall modelling approach allows the comparison of model behavior for the different regions and may provide insights on the main dynamic processes driving the interaction between vegetation and climate within different regions. The data employed in this study encompasses the global datasets for soil properties (SoilGrids), terrain properties (Global Relief Model based on SRTM DEM and ETOPO), monthly time series of satellite-derived vegetation indices (GIMMS NDVI3g) and climate variables (Princeton Meteorological Forcing Dataset). The findings proved the potential of a spatio-temporal Bayesian modelling approach for assessing vegetation dynamics, at a regional scale. The observed interrelationships of the employed data and the different spatial and temporal trends support our hypothesis. That is, the change of vegetation in space and time may be better understood when modelling vegetation change as both a dynamic and multivariate process. Therefore, future research will focus on a multivariate dynamical spatio-temporal modelling approach. This ongoing research is performed within the context of the project "Global impacts of hydrological and climatic extremes on vegetation" (project acronym: SAT-EX) which is part of the Belgian research programme for Earth Observation Stereo III.

A Geographic Information Science (GISc) Approach to Characterizing Spatiotemporal Patterns of Terrorist Incidents in Iraq, 2004-2009

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

Medina, Richard M; Siebeneck, Laura K.; Hepner, George F.

2011-01-01

As terrorism on all scales continues, it is necessary to improve understanding of terrorist and insurgent activities. This article takes a Geographic Information Systems (GIS) approach to advance the understanding of spatial, social, political, and cultural triggers that influence terrorism incidents. Spatial, temporal, and spatiotemporal patterns of terrorist attacks are examined to improve knowledge about terrorist systems of training, planning, and actions. The results of this study aim to provide a foundation for understanding attack patterns and tactics in emerging havens as well as inform the creation and implementation of various counterterrorism measures.

Conformable actively multiplexed high-density surface electrode array for brain interfacing

DOEpatents

Rogers, John; Kim, Dae-Hyeong; Litt, Brian; Viventi, Jonathan

2015-01-13

Provided are methods and devices for interfacing with brain tissue, specifically for monitoring and/or actuation of spatio-temporal electrical waveforms. The device is conformable having a high electrode density and high spatial and temporal resolution. A conformable substrate supports a conformable electronic circuit and a barrier layer. Electrodes are positioned to provide electrical contact with a brain tissue. A controller monitors or actuates the electrodes, thereby interfacing with the brain tissue. In an aspect, methods are provided to monitor or actuate spatio-temporal electrical waveform over large brain surface areas by any of the devices disclosed herein.

TNFRSF14 aberrations in follicular lymphoma increase clinically significant allogeneic T-cell responses.

PubMed

Kotsiou, Eleni; Okosun, Jessica; Besley, Caroline; Iqbal, Sameena; Matthews, Janet; Fitzgibbon, Jude; Gribben, John G; Davies, Jeffrey K

2016-07-07

Donor T-cell immune responses can eradicate lymphomas after allogeneic hematopoietic stem cell transplantation (AHSCT), but can also damage healthy tissues resulting in harmful graft-versus-host disease (GVHD). Next-generation sequencing has recently identified many new genetic lesions in follicular lymphoma (FL). One such gene, tumor necrosis factor receptor superfamily 14 (TNFRSF14), abnormal in 40% of FL patients, encodes the herpes virus entry mediator (HVEM) which limits T-cell activation via ligation of the B- and T-lymphocyte attenuator. As lymphoma B cells can act as antigen-presenting cells, we hypothesized that TNFRSF14 aberrations that reduce HVEM expression could alter the capacity of FL B cells to stimulate allogeneic T-cell responses and impact the outcome of AHSCT. In an in vitro model of alloreactivity, human lymphoma B cells with TNFRSF14 aberrations had reduced HVEM expression and greater alloantigen-presenting capacity than wild-type lymphoma B cells. The increased immune-stimulatory capacity of lymphoma B cells with TNFRSF14 aberrations had clinical relevance, associating with higher incidence of acute GVHD in patients undergoing AHSCT. FL patients with TNFRSF14 aberrations may benefit from more aggressive immunosuppression to reduce harmful GVHD after transplantation. Importantly, this study is the first to demonstrate the impact of an acquired genetic lesion on the capacity of tumor cells to stimulate allogeneic T-cell immune responses which may have wider consequences for adoptive immunotherapy strategies. © 2016 by The American Society of Hematology.

Exposure related mutagens in urine of rubber workers associated with inhalable particulate and dermal exposure

PubMed Central

Vermeulen, R; Bos, R; Pertijs, J; Kromhout, H

2003-01-01

Aims: To determine the relation of the inhalation and dermal exposure routes and mutagenic activity in the urine of rubber workers (n = 105). Methods: Mutagenic activity of ambient total suspended particulate matter (TSPM), surface contamination wipes, and Sunday and weekday urine samples was assessed with S typhimurium YG1041 in the presence of a metabolic activation system. Each subject was grouped into one of two exposure categories for dermal exposure (high (≥25 revertants/cm2), low (<25 revertants/cm2)) based on the mutagenic activity detected on likely skin contact surfaces and into two airborne mutagenic exposure categories (high (≥210 revertants/m3), low (<210 revertants/m3)). The potential influence of skin aberrations and acetylation status (NAT2) on urinary mutagenicity levels was also evaluated. Results: A non-significant increase of +1605 revertants/g creatinine in urinary mutagenicity during the workweek relative to levels observed on Sunday was observed for the total population. Subsequent multivariate regression analyses, with the subjects' weekday urinary mutagenicity levels as the dependent variable, revealed associations with environmental and mainstream tobacco smoke exposure, with the level of mutagenic contamination on surfaces with which the subjects had likely contact, with the subjects' inhalable particulate exposure level, with observed mild skin aberrations, and when the subjects had a slow acetylation phenotype. Similar associations, although weaker were observed with Sunday urinary mutagenicity levels as well, except for the association with slow acetylation phenotype. Based on measured exposure levels it could be estimated that a high potential for exposure to surface contamination with mutagenic activity increased weekday urinary mutagenicity by about 62% when compared to low exposed workers, while high inhalable particulate exposure levels increased weekday urinary mutagenicity levels by about 21%. Subjects with mild skin aberrations had an additional, non-significant, increase in weekday urinary mutagenic activity compared to subjects without any skin aberrations. Discussion: Results suggest that the dermal exposure route may contribute more to the level of genotoxic compounds in urine of rubber workers than the inhalation route. Although the study was limited in size, the results warrant further investigation in the importance of and ways to effectively control the dermal exposure route in the rubber industry. PMID:12554836

Nonlinear analyses of interictal EEG map the brain interdependences in human focal epilepsy

NASA Astrophysics Data System (ADS)

Quyen, Michel Le Van; Martinerie, Jacques; Adam, Claude; Varela, Francisco J.

1999-03-01

The degree of interdependence between intracranial electroencephalographic (EEG) channels was investigated in epileptic patients with temporal lobe seizures during interictal (between seizures) periods. With a novel method to characterize nonlinear cross-predictability, that is, the predictability of one channel using another channel as data base, we demonstrated here a possibility to extract information on the spatio-temporal organization of interactions between multichannel recording sites. This method determines whether two channels contain common activity, and often, whether one channel contains activity induced by the activity of the other channel. In particular, the technique and the comparison with surrogate data demonstrated that transient large-scale nonlinear entrainments by the epileptogenic region can be identified, this with or without epileptic activity. Furthermore, these recurrent activities related with the epileptic foci occurred in well-defined spatio-temporal patterns. This suggests that the epileptogenic region can exhibit very subtle influences on other brain regions during an interictal period and raises the possibility that the cross-predictability analysis of interictal data may be used as a significant aid in locating epileptogenic foci.

Photo-triggered fluorescent theranostic prodrugs as DNA alkylating agents for mechlorethamine release and spatiotemporal monitoring.

PubMed

Cao, Yanting; Pan, Rong; Xuan, Weimin; Wei, Yongyi; Liu, Kejian; Zhou, Jiahong; Wang, Wei

2015-06-28

We describe a new theranostic strategy for selective delivery and spatiotemporal monitoring of mechlorethamine, a DNA alkylating agent. A photo-responsive prodrug is designed and composed of a photolabile o-nitrophenylethyl group, a DNA alkylating mechlorethamine drug and a coumarin fluorophore. Masking of the "N" in mechlorethamine in a positively charged state in the prodrug renders it inactive, non-toxic, selective and non-fluorescent. Indeed, the stable prodrug shows negligible cytotoxicity towards normal cells with and without UV activation and is completely non-fluorescent. However, upon photo-irradiation, the active mechlorethamine is released and induces efficient DNA cross-links, accompanied by a strong fluorescence enhancement (152 fold). Furthermore, DNA cross-linking activity from the release can be transformed into anticancer activity observed in in vitro studies of tumor cells. Importantly, the drug release progress and the movement can be conveniently monitored by fluorescence spectroscopy. The mechanistic study proves that the DNA cross-linking activity is mainly due to the release of DNA alkylating mechlorethamine. Altogether, the studies show the power of the theranostic strategy for efficient therapy in cancer treatment.

Application research on temporal GIS in the transportation information management system

NASA Astrophysics Data System (ADS)

Wang, Wei; Qin, Qianqing; Wang, Chao

2006-10-01

The application, development and key matters of applying spatio-temporal GIS to traffic information management system are discussed in this paper by introducing the development of spatio-temporal database, current models of spatio-temporal data, traits of traffic information management system. This paper proposes a method of organizing spatio-temporal data taking road object changes into consideration, and describes its data structure in 3 aspects, including structure of spatio-temporal object, organizing method spatio-temporal data and storage means of spatio-temporal data. Trying to manage types of spatio-temporal data involved in traffic system, such as road information, river information, railway information, social and economical data, and etc, uniformly, efficiently and with low redundancy.

Spatiotemporal profiles of receptive fields of neurons in the lateral posterior nucleus of the cat LP-pulvinar complex.

PubMed

Piché, Marilyse; Thomas, Sébastien; Casanova, Christian

2015-10-01

The pulvinar is the largest extrageniculate thalamic visual nucleus in mammals. It establishes reciprocal connections with virtually all visual cortexes and likely plays a role in transthalamic cortico-cortical communication. In cats, the lateral posterior nucleus (LP) of the LP-pulvinar complex can be subdivided in two subregions, the lateral (LPl) and medial (LPm) parts, which receive a predominant input from the striate cortex and the superior colliculus, respectively. Here, we revisit the receptive field structure of LPl and LPm cells in anesthetized cats by determining their first-order spatiotemporal profiles through reverse correlation analysis following sparse noise stimulation. Our data reveal the existence of previously unidentified receptive field profiles in the LP nucleus both in space and time domains. While some cells responded to only one stimulus polarity, the majority of neurons had receptive fields comprised of bright and dark responsive subfields. For these neurons, dark subfields' size was larger than that of bright subfields. A variety of receptive field spatial organization types were identified, ranging from totally overlapped to segregated bright and dark subfields. In the time domain, a large spectrum of activity overlap was found, from cells with temporally coinciding subfield activity to neurons with distinct, time-dissociated subfield peak activity windows. We also found LP neurons with space-time inseparable receptive fields and neurons with multiple activity periods. Finally, a substantial degree of homology was found between LPl and LPm first-order receptive field spatiotemporal profiles, suggesting a high integration of cortical and subcortical inputs within the LP-pulvinar complex. Copyright © 2015 the American Physiological Society.

Automated detection of qualitative spatio-temporal features in electrocardiac activation maps.

PubMed

Ironi, Liliana; Tentoni, Stefania

2007-02-01

This paper describes a piece of work aiming at the realization of a tool for the automated interpretation of electrocardiac maps. Such maps can capture a number of electrical conduction pathologies, such as arrhytmia, that can be missed by the analysis of traditional electrocardiograms. But, their introduction into the clinical practice is still far away as their interpretation requires skills that belongs to very few experts. Then, an automated interpretation tool would bridge the gap between the established research outcome and clinical practice with a consequent great impact on health care. Qualitative spatial reasoning can play a crucial role in the identification of spatio-temporal patterns and salient features that characterize the heart electrical activity. We adopted the spatial aggregation (SA) conceptual framework and an interplay of numerical and qualitative information to extract features from epicardial maps, and to make them available for reasoning tasks. Our focus is on epicardial activation isochrone maps as they are a synthetic representation of spatio-temporal aspects of the propagation of the electrical excitation. We provide a computational SA-based methodology to extract, from 3D epicardial data gathered over time, (1) the excitation wavefront structure, and (2) the salient features that characterize wavefront propagation and visually correspond to specific geometric objects. The proposed methodology provides a robust and efficient way to identify salient pieces of information in activation time maps. The hierarchical structure of the abstracted geometric objects, crucial in capturing the prominent information, facilitates the definition of general rules necessary to infer the correlation between pathophysiological patterns and wavefront structure and propagation.

Spatio-temporal activity of lightnings over Greece

NASA Astrophysics Data System (ADS)

Nastos, P. T.; Matsangouras, I. T.; Chronis, T. G.

2012-04-01

Extreme precipitation events are always associated with convective weather conditions driving to intense lightning activity: Cloud to Ground (CG), Ground to Cloud (GC) and Cloud to Cloud (CC). Thus, the study of lightnings, which typically occur during thunderstorms, gives evidence of the spatio-temporal variability of intense precipitation. Lightning is a natural phenomenon in the atmosphere, being a major cause of storm related with deaths and main trigger of forest fires during dry season. Lightning affects the many electrochemical systems of the body causing nerve damage, memory loss, personality change, and emotional problems. Besides, among the various nitrogen oxides sources, the contribution from lightning likely represents the largest uncertainty. An operational lightning detection network (LDN) has been established since 2007 by HNMS, consisting of eight time-of-arrival sensors (TOA), spatially distributed across Greek territory. In this study, the spatial and temporal variability of recorded lightnings (CG, GC and CC) are analyzed over Greece, during the period from January 14, 2008 to December 31, 2009, for the first time. The data for retrieving the location and time-of-occurrence of lightning were acquired from Hellenic National Meteorological Service (HNMS). In addition to the analysis of spatio-temporal activity over Greece, the HNMS-LDN characteristics are also presented. The results of the performed analysis reveal the specific geographical sub-regions associated with lightnings incidence. Lightning activity occurs mainly during the autumn season, followed by summer and spring. Higher frequencies of flashes appear over Ionian and Aegean Sea than over land during winter period against continental mountainous regions during summer period.

Refractive Changes Induced by Spherical Aberration in Laser Correction Procedures: An Adaptive Optics Study.

PubMed

Amigó, Alfredo; Martinez-Sorribes, Paula; Recuerda, Margarita

2017-07-01

To study the effect on vision of induced negative and positive spherical aberration within the range of laser vision correction procedures. In 10 eyes (mean age: 35.8 years) under cyclopegic conditions, spherical aberration values from -0.75 to +0.75 µm in 0.25-µm steps were induced by an adaptive optics system. Astigmatism and spherical refraction were corrected, whereas the other natural aberrations remained untouched. Visual acuity, depth of focus defined as the interval of vision for which the target was still perceived acceptable, contrast sensitivity, and change in spherical refraction associated with the variation in pupil diameter from 6 to 2.5 mm were measured. A refractive change of 1.60 D/µm of induced spherical aberration was obtained. Emmetropic eyes became myopic when positive spherical aberration was induced and hyperopic when negative spherical aberration was induced (R 2 = 81%). There were weak correlations between spherical aberration and visual acuity or depth of focus (R 2 = 2% and 3%, respectively). Contrast sensitivity worsened with the increment of spherical aberration (R 2 = 59%). When pupil size decreased, emmetropic eyes became hyperopic when preexisting spherical aberration was positive and myopic when spherical aberration was negative, with an average refractive change of 0.60 D/µm of spherical aberration (R 2 = 54%). An inverse linear correlation exists between the refractive state of the eye and spherical aberration induced within the range of laser vision correction. Small values of spherical aberration do not worsen visual acuity or depth of focus, but positive spherical aberration may induce night myopia. In addition, the changes in spherical refraction when the pupil constricts may worsen near vision when positive spherical aberration is induced or improve it when spherical aberration is negative. [J Refract Surg. 2017;33(7):470-474.]. Copyright 2017, SLACK Incorporated.

Autophagy-dependent generation of Axin2+ cancer stem-like cells promotes hepatocarcinogenesis in liver cirrhosis.

PubMed

Li, J; Hu, S B; Wang, L Y; Zhang, X; Zhou, X; Yang, B; Li, J H; Xiong, J; Liu, N; Li, Y; Wu, Y Z; Zheng, Q C

2017-11-30

Autophagy is a pathophysiological phenomenon in liver cirrhosis that can further progress into hepatocarcinoma. Liver cancer stem cells (CSCs) are believed to initiate hepatocarcinogenesis. To investigate the precise mechanism related to the origin of CSCs in liver cirrhosis and hepatocarcinogenesis, we labeled Axin2+ hepatic cells with EGFP in Axin2Cre;Rosa26EGFP transgenic rats, and then stratified clinical and rat liver cirrhosis samples by autophagy flux. Clinical follow-up and lineage tracing in transgenic rat liver cirrhosis revealed that while Axin2/EGFP+ hepatic cells were present in normal livers and cirrhotic livers without aberrant autophagy, hepatic Axin2/EGFP+CD90+ cells were generated exclusively in cirrhotic livers with aberrant autophagy and promoted hepatocarcinogenesis. Aberrant autophagy in liver cirrhosis resulted in hepatocyte growth factor (HGF) expression, leading to activation of Met/JNK and Met/STAT3 signaling in sorted hepatic Axin2/EGFP+ cells and their transition into Axin2/EGFP+CD90+ cells that possess CSC properties. In a transgenic rat liver cirrhosis model, induction or inhibition of autophagy in cirrhotic livers by systemic administration of rapamycin or chloroquine or transfection with Atg3- and Atg7-shRNAs significantly induced or suppressed HGF expression, which in turn increased or reduced generation of EGFP+CD90+ hepatic cells by activating or inactivating Met/JNK and Met/STAT3 signaling, thereby promoting or preventing hepatocarcinogenesis. Systemic treatment with HGF-shRNA, SP600125 or stattic also reduced generation of EGFP(Axin2)+ hepatic cell-originated CD90+ CSCs in aberrant autophagic cirrhotic livers by inactivating HGF/Met/JNK or HGF/Met/STAT3 signaling, further preventing hepatocarcinogenesis. These data suggest that activation of Met/JNK and Met/STAT3 signaling in Axin2+ hepatic cells via autophagy-dependent HGF expression and the resultant generation of Axin2+CD90+ CSCs is a major mechanism of hepatocarcinogenesis in cirrhotic livers.

Autophagy-dependent generation of Axin2+ cancer stem-like cells promotes hepatocarcinogenesis in liver cirrhosis

PubMed Central

Li, J; Hu, S B; Wang, L Y; Zhang, X; Zhou, X; Yang, B; Li, J H; Xiong, J; Liu, N; Li, Y; Wu, Y Z; Zheng, Q C

2017-01-01

Autophagy is a pathophysiological phenomenon in liver cirrhosis that can further progress into hepatocarcinoma. Liver cancer stem cells (CSCs) are believed to initiate hepatocarcinogenesis. To investigate the precise mechanism related to the origin of CSCs in liver cirrhosis and hepatocarcinogenesis, we labeled Axin2+ hepatic cells with EGFP in Axin2Cre;Rosa26EGFP transgenic rats, and then stratified clinical and rat liver cirrhosis samples by autophagy flux. Clinical follow-up and lineage tracing in transgenic rat liver cirrhosis revealed that while Axin2/EGFP+ hepatic cells were present in normal livers and cirrhotic livers without aberrant autophagy, hepatic Axin2/EGFP+CD90+ cells were generated exclusively in cirrhotic livers with aberrant autophagy and promoted hepatocarcinogenesis. Aberrant autophagy in liver cirrhosis resulted in hepatocyte growth factor (HGF) expression, leading to activation of Met/JNK and Met/STAT3 signaling in sorted hepatic Axin2/EGFP+ cells and their transition into Axin2/EGFP+CD90+ cells that possess CSC properties. In a transgenic rat liver cirrhosis model, induction or inhibition of autophagy in cirrhotic livers by systemic administration of rapamycin or chloroquine or transfection with Atg3- and Atg7-shRNAs significantly induced or suppressed HGF expression, which in turn increased or reduced generation of EGFP+CD90+ hepatic cells by activating or inactivating Met/JNK and Met/STAT3 signaling, thereby promoting or preventing hepatocarcinogenesis. Systemic treatment with HGF-shRNA, SP600125 or stattic also reduced generation of EGFP(Axin2)+ hepatic cell-originated CD90+ CSCs in aberrant autophagic cirrhotic livers by inactivating HGF/Met/JNK or HGF/Met/STAT3 signaling, further preventing hepatocarcinogenesis. These data suggest that activation of Met/JNK and Met/STAT3 signaling in Axin2+ hepatic cells via autophagy-dependent HGF expression and the resultant generation of Axin2+CD90+ CSCs is a major mechanism of hepatocarcinogenesis in cirrhotic livers. PMID:28783177

Lethality of radiation-induced chromosome aberrations in human tumour cell lines with different radiosensitivities.

PubMed

Coco-Martin, J M; Ottenheim, C P; Bartelink, H; Begg, A C

1996-03-01

In order to find an explanation for the eventual disappearance of all chromosome aberrations in two radiosensitive human tumour cell lines, the type and stability of different aberration types was investigated in more detail. To classify the aberrations into unstable and stable types, three-colour fluorescence in situ hybridization was performed, including a whole-chromosome probe, a pancentromere probe, and a stain for total DNA. This technique enables the appropriate classification of the aberrations principally by the presence (stable) or not (unstable) of a single centromere per chromosome. Unstable-type aberrations were found to disappear within 7 days (several divisions) in the two radiosensitive and the two radioresistant tumour lines investigated. Stable-type aberrations were found to remain at an approximately constant level over the duration of the experiment (14 days; 8-10 divisions) in the two radioresistant lines. In contrast, the majority of these stable-type aberrations had disappeared by 14 days in the two radiosensitive lines. The previous findings of disappearance of total aberrations in radiosensitive cells was therefore not due to a reduced induction of stable-type aberrations, but the complete disappearance of cells with this aberration type. These results could not be explained by differences in apoptosis or G1 blocks. Two possible explanations for these unexpected findings involve non-random induction of unstable-type aberrations, or lethality of stable-type aberrations. The results suggest caution in the use of stable-type aberration numbers as a predictor for radiosensitivity.

Spatiotemporal Data Organization and Application Research

NASA Astrophysics Data System (ADS)

Tan, C.; Yan, S.

2017-09-01

Organization and management of spatiotemporal data is a key support technology for intelligence in all fields of the smart city. The construction of a smart city cannot be realized without spatiotemporal data. Oriented to support intelligent applications this paper proposes an organizational model for spatiotemporal data, and details the construction of a spatiotemporal big data calculation, analysis, and service framework for highly efficient management and intelligent application of spatiotemporal data for the entire data life cycle.

Activation of PPAR{delta} up-regulates fatty acid oxidation and energy uncoupling genes of mitochondria and reduces palmitate-induced apoptosis in pancreatic {beta}-cells

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

Wan, Jun; Jiang, Li; Lue, Qingguo

2010-01-15

Recent evidence indicates that decreased oxidative capacity, lipotoxicity, and mitochondrial aberrations contribute to the development of insulin resistance and type 2 diabetes. The goal of this study was to investigate the effects of peroxisome proliferator-activated receptor {delta} (PPAR{delta}) activation on lipid oxidation, mitochondrial function, and insulin secretion in pancreatic {beta}-cells. After HIT-T15 cells (a {beta}-cell line) were exposed to high concentrations of palmitate and GW501516 (GW; a selective agonist of PPAR{delta}), we found that administration of GW increased the expression of PPAR{delta} mRNA. GW-induced activation of PPAR{delta} up-regulated carnitine palmitoyltransferase 1 (CPT1), long-chain acyl-CoA dehydrogenase (LCAD), pyruvate dehydrogenase kinase 4more » (PDK4), and uncoupling protein 2 (UCP2); alleviated mitochondrial swelling; attenuated apoptosis; and reduced basal insulin secretion induced by increased palmitate in HIT cells. These results suggest that activation of PPAR{delta} plays an important role in protecting pancreatic {beta}-cells against aberrations caused by lipotoxicity in metabolic syndrome and diabetes.« less

LC3 binding to the scaffolding protein JIP1 regulates processive dynein-driven transport of autophagosomes.

PubMed

Fu, Meng-Meng; Nirschl, Jeffrey J; Holzbaur, Erika L F

2014-06-09

Autophagy is essential for maintaining cellular homeostasis in neurons, where autophagosomes undergo robust unidirectional retrograde transport along axons. We find that the motor scaffolding protein JIP1 binds directly to the autophagosome adaptor LC3 via a conserved LIR motif. This interaction is required for the initial exit of autophagosomes from the distal axon, for sustained retrograde transport along the midaxon, and for autophagosomal maturation in the proximal axon. JIP1 binds directly to the dynein activator dynactin but also binds to and activates kinesin-1 in a phosphorylation-dependent manner. Following JIP1 depletion, phosphodeficient JIP1-S421A rescues retrograde transport, while phosphomimetic JIP1-S421D aberrantly activates anterograde transport. During normal autophagosome transport, residue S421 of JIP1 may be maintained in a dephosphorylated state by autophagosome-associated MKP1 phosphatase. Moreover, binding of LC3 to JIP1 competitively disrupts JIP1-mediated activation of kinesin. Thus, dual mechanisms prevent aberrant activation of kinesin to ensure robust retrograde transport of autophagosomes along the axon. Copyright © 2014 Elsevier Inc. All rights reserved.

Wavefront aberrations of x-ray dynamical diffraction beams.

PubMed

Liao, Keliang; Hong, Youli; Sheng, Weifan

2014-10-01

The effects of dynamical diffraction in x-ray diffractive optics with large numerical aperture render the wavefront aberrations difficult to describe using the aberration polynomials, yet knowledge of them plays an important role in a vast variety of scientific problems ranging from optical testing to adaptive optics. Although the diffraction theory of optical aberrations was established decades ago, its application in the area of x-ray dynamical diffraction theory (DDT) is still lacking. Here, we conduct a theoretical study on the aberration properties of x-ray dynamical diffraction beams. By treating the modulus of the complex envelope as the amplitude weight function in the orthogonalization procedure, we generalize the nonrecursive matrix method for the determination of orthonormal aberration polynomials, wherein Zernike DDT and Legendre DDT polynomials are proposed. As an example, we investigate the aberration evolution inside a tilted multilayer Laue lens. The corresponding Legendre DDT polynomials are obtained numerically, which represent balanced aberrations yielding minimum variance of the classical aberrations of an anamorphic optical system. The balancing of classical aberrations and their standard deviations are discussed. We also present the Strehl ratio of the primary and secondary balanced aberrations.

Influence of Misalignment on High-Order Aberration Correction for Normal Human Eyes

NASA Astrophysics Data System (ADS)

Zhao, Hao-Xin; Xu, Bing; Xue, Li-Xia; Dai, Yun; Liu, Qian; Rao, Xue-Jun

2008-04-01

Although a compensation device can correct aberrations of human eyes, the effect will be degraded by its misalignment, especially for high-order aberration correction. We calculate the positioning tolerance of correction device for high-order aberrations, and within what degree the correcting effect is better than low-order aberration (defocus and astigmatism) correction. With fixed certain misalignment within the positioning tolerance, we calculate the residual wavefront rms aberration of the first-6 to first-35 terms along with the 3rd-5th terms of aberrations corrected, and the combined first-13 terms of aberrations are also studied under the same quantity of misalignment. However, the correction effect of high-order aberrations does not meliorate along with the increase of the high-order terms under some misalignment, moreover, some simple combined terms correction can achieve similar result as complex combinations. These results suggest that it is unnecessary to correct too much the terms of high-order aberrations which are difficult to accomplish in practice, and gives confidence to correct high-order aberrations out of the laboratory.

Activation of D4 dopamine receptor decreases AT1 angiotensin II receptor expression in rat renal proximal tubule cells

PubMed Central

Chen, Ken; Deng, Kun; Wang, Xiaoyan; Wang, Zhen; Zheng, Shuo; Ren, Hongmei; He, Duofen; Han, Yu; Asico, Laureano D.; Jose, Pedro A.; Zeng, Chunyu

2014-01-01

The dopaminergic and renin angiotensin systems interact to regulate blood pressure. Disruption of the D4 dopamine receptor gene in mice produces hypertension that is associated with increased renal AT1 receptor expression. We hypothesize that the D4 receptor can inhibit AT1 receptor expression and function in renal proximal tubules (RPTs) cells from Wistar-Kyoto (WKY) rats but the D4 receptor regulation of AT1 receptor is aberrant in RPT cells from spontaneously hypertensive rats (SHRs). The D4 receptor agonist, PD168077, decreased AT1 receptor protein expression in a time and concentration-dependent manner in WKY cells. By contrast, in SHR cells, PD168077 increased AT1 receptor protein expression. The inhibitory effect of D4 receptor on AT1 receptor expression in WKY cells was blocked by a calcium channel blocker, nicardipine, or calcium-free medium, indicating that calcium is involved in the D4 receptor-mediated signaling pathway. Angiotensin II increased Na+-K+ ATPase activity in WKY cells. Pretreatment with PD168077 decreased the stimulatory effect of angiotensin II on Na+-K+ ATPase activity in WKY cells. In SHR cells, the inhibitory effect of D4 receptor on angiotensin II-mediated stimulation of Na+-K+ ATPase activity was aberrant; pretreatment with PD168077 augmented the stimulatory effect of AT1 receptor on Na+-K+ ATPase activity in SHR cells. This was confirmed in vivo; pre-treatment with PD128077 for one week augmented the anti-hypertensive and natriuretic effect of losartan in SHRs but not in WKY rats. We suggest that an aberrant interaction between D4 and AT1 receptors may play a role in the abnormal regulation of sodium excretion in hypertension. PMID:25368031

Mitochondrial GRIM-19 as a potential therapeutic target for STAT3-dependent carcinogenesis of gastric cancer

PubMed Central

Zhao, Xiaodong; Bao, Liming; Huang, Daochao; Song, Lihua; Li, Yang

2016-01-01

Aberrant STAT3 activation occurs in most human gastric cancers (GCs) and contributes to the malignant progression of GC, but mechanism(s) underlying aberrant STAT3 remain largely unknown. Here we demonstrated that the gene associated with retinoid interferon-induced mortality 19 (GRIM-19) was severely depressed or lost in GC and chronic atrophic gastritis (CAG) tissues and its loss contributed to GC tumorigenesis partly by activating STAT3 signaling. In primary human GC tissues, GRIM-19 was frequently depressed or lost and this loss correlated with advanced clinical stage, lymph node metastasis, H. pylori infection and poor overall survival of GC patients. In CAG tissues, GRIM-19 was progressively decreased along with its malignant transformation. Functionally, we indentified an oncogenic role of GRIM-19 loss in promoting GC tumorigenesis. Ectopic GRIM-19 expression suppressed GC tumor formation in vitro and in vivo by inducing cell cycle arrest and apoptosis. Moreover, we revealed that GRIM-19 inhibited STAT3 transcriptional activation and its downstream targets by reducing STAT3 nuclear distribution. Conversely, knockdown of GRIM-19 induced aberrant STAT3 activation and accelerated GC cell growth in vitro and in vivo, and this could be partly attenuated by the blockage of STAT3 activation. In addition, we observed subcellular redistributions of GRIM-19 characterized by peri-nuclear aggregates, non-mitochondria cytoplasmic distribution and nuclear invasion, which should be responsible for reduced STAT3 nuclear distribution. Our studies suggest that mitochondrial GRIM-19 could not only serve as an valuable prognostic biomarker for GC development, but also as a potential therapeutic target for STAT3-dependent carcinogenesis of GC. PMID:27167343

Aberrantly Expressed OTX Homeobox Genes Deregulate B-Cell Differentiation in Hodgkin Lymphoma.

PubMed

Nagel, Stefan; Ehrentraut, Stefan; Meyer, Corinna; Kaufmann, Maren; Drexler, Hans G; MacLeod, Roderick A F

2015-01-01

In Hodgkin lymphoma (HL) we recently reported that deregulated homeobox gene MSX1 mediates repression of the B-cell specific transcription factor ZHX2. In this study we investigated regulation of MSX1 in this B-cell malignancy. Accordingly, we analyzed expression and function of OTX homeobox genes which activate MSX1 transcription during embryonal development in the neural plate border region. Our data demonstrate that OTX1 and OTX2 are aberrantly expressed in both HL patients and cell lines. Moreover, both OTX loci are targeted by genomic gains in overexpressing cell lines. Comparative expression profiling and subsequent pathway modulations in HL cell lines indicated that aberrantly enhanced FGF2-signalling activates the expression of OTX2. Downstream analyses of OTX2 demonstrated transcriptional activation of genes encoding transcription factors MSX1, FOXC1 and ZHX1. Interestingly, examination of the physiological expression profile of ZHX1 in normal hematopoietic cells revealed elevated levels in T-cells and reduced expression in B-cells, indicating a discriminatory role in lymphopoiesis. Furthermore, two OTX-negative HL cell lines overexpressed ZHX1 in correlation with genomic amplification of its locus at chromosomal band 8q24, supporting the oncogenic potential of this gene in HL. Taken together, our data demonstrate that deregulated homeobox genes MSX1 and OTX2 respectively impact transcriptional inhibition of (B-cell specific) ZHX2 and activation of (T-cell specific) ZHX1. Thus, we show how reactivation of a specific embryonal gene regulatory network promotes disturbed B-cell differentiation in HL.

Genotoxicity assessment of ethylenediamine dinitrate (EDDN) and diethylenetriamine trinitrate (DETN).

PubMed

Reddy, Gunda; Song, Jian; Kirby, Paul; Johnson, Mark S

2011-12-24

Ethylenediamine dinitrate (EDDN) and diethylenetriamine trinitrate (DETN) are relatively insensitive explosive compounds that are being explored as safe alternatives to other more sensitive compounds. When used in combination with other high explosives they are an improvement and may provide additional safety during storage and use. The genetic toxicity of these compounds was evaluated to predict the potential adverse human health effects from exposure by using a standard genetic toxicity test battery which included: a gene mutation test in bacteria (Ames), an in vitro Chinese Hamster Ovary (CHO) cell chromosome aberration test and an in vivo mouse micronucleus test. The results of the Ames test showed that EDDN increased the mean number of revertants per plate with strain TA100, without activation, at 5000μg/plate compared to the solvent control, which indicated a positive result. No positive results were observed with the other tester strains with or without activation in Salmonella typhimurium strains TA98, TA1535, TA1537, and Escherichia coli strain WP2 uvrA. DETN was negative for all Salmonella tester strains and E. coli up to 5000μg/plate both with and without metabolic activation. The CHO cell chromosome aberration assay was performed using EDDN and DETN at concentrations up to 5000μg/mL. The results indicate that these compounds did not induce structural chromosomal aberrations at all tested concentrations in CHO cells, with or without metabolic activation. EDDN and DETN, when tested in vivo in the CD-1 mouse at doses up to 2000mg/kg, did not induce any significant increase in the number of micronuclei in bone marrow erythrocytes. These studies demonstrate that EDDN is mutagenic in one strain of Salmonella (TA100) but was negative in other strains, for in vitro induction of chromosomal aberrations in CHO cells, and for micronuclei in the in vivo mouse micronucleus assay. DETN was not genotoxic in all in vitro and in vivo tests. These results show the in vitro and in vivo genotoxicity potential of these chemicals. Copyright © 2011 Elsevier B.V. All rights reserved.

Spatio-temporal distribution of soil nitrogen in Poyang lake ecological economic zone (South-China).

PubMed

Jiang, Yefeng; Rao, Lei; Sun, Kai; Han, Yi; Guo, Xi

2018-06-01

Revealing the spatio-temporal distribution of soil nitrogen (N) contributes to N management and prevention of N pollution. The objective of this work is to study the spatio-temporal distribution of soil N and their driving factors in the topsoil (0-20 cm) of farmland in Yugan county, China in 1982 and 2012. Data were collected from 200 sampling sites of the second national soil survey in Yugan in 1982 and 423 sampling sites of the soil testing and formula fertilization project in 2012. On average total N (TN) and available N (AN) significantly increased from 1.50 g kg -1 and 153.04 mg kg -1 in 1982 to 1.58 g kg -1 and 179.75 mg kg -1 in 2012, respectively. The distance of spatial autocorrelation for TN increased from 2.79 to 6.18 km and from 2.97 to 18.00 km for AN from 1982 to 2012. The nugget/sill ratio for TN (0.472 in 1982 and 0.581 in 2012) indicated that soil TN driving by natural characteristics in 1982 to human activities in 2012. The nugget/sill ratio for soil AN (0.471 in 1982 and 0.688 in 2012) indicated that soil AN is more influenced by human activities. The major factors driving the spatio-temporal distribution of soil N was N application rate. To promote the sustainable development of agriculture and eco-environment, we should improve the awareness of farmers on chemical fertilizers (particularly N) and the level of N fertilizer management, increase the use of manure and organic fertilizer and facilitate rational fertilization by farmers. Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.

An origin of the immunogenicity of in vitro transcribed RNA.

PubMed

Mu, Xin; Greenwald, Emily; Ahmad, Sadeem; Hur, Sun

2018-06-01

The emergence of RNA-based therapeutics demands robust and economical methods to produce RNA with few byproducts from aberrant activity. While in vitro transcription using the bacteriophage T7 RNA polymerase is one such popular method, its transcripts are known to display an immune-stimulatory activity that is often undesirable and uncontrollable. We here showed that the immune-stimulatory activity of T7 transcript is contributed by its aberrant activity to initiate transcription from a promoter-less DNA end. This activity results in the production of an antisense RNA that is fully complementary to the intended sense RNA product, and consequently a long double-stranded RNA (dsRNA) that can robustly stimulate a cytosolic pattern recognition receptor, MDA5. This promoter-independent transcriptional activity of the T7 RNA polymerase was observed for a wide range of DNA sequences and lengths, but can be suppressed by altering the transcription reaction with modified nucleotides or by reducing the Mg2+ concentration. The current work thus not only offers a previously unappreciated mechanism by which T7 transcripts stimulate the innate immune system, but also shows that the immune-stimulatory activity can be readily regulated.

Human eyes do not need monochromatic aberrations for dynamic accommodation.

PubMed

Bernal-Molina, Paula; Marín-Franch, Iván; Del Águila-Carrasco, Antonio J; Esteve-Taboada, Jose J; López-Gil, Norberto; Kruger, Philip B; Montés-Micó, Robert

2017-09-01

To determine if human accommodation uses the eye's own monochromatic aberrations to track dynamic accommodative stimuli. Wavefront aberrations were measured while subjects monocularly viewed a monochromatic Maltese cross moving sinusoidally around 2D of accommodative demand with 1D amplitude at 0.2 Hz. The amplitude and phase (delay) of the accommodation response were compared to the actual vergence of the stimulus to obtain gain and temporal phase, calculated from wavefront aberrations recorded over time during experimental trials. The tested conditions were as follows: Correction of all the subject's aberrations except defocus (C); Correction of all the subject's aberrations except defocus and habitual second-order astigmatism (AS); Correction of all the subject's aberrations except defocus and odd higher-order aberrations (HOAs); Correction of all the subject's aberrations except defocus and even HOAs (E); Natural aberrations of the subject's eye, i.e., the adaptive-optics system only corrected the optical system's aberrations (N); Correction of all the subject's aberrations except defocus and fourth-order spherical aberration (SA). The correction was performed at 20 Hz and each condition was repeated six times in randomised order. Average gain (±2 standard errors of the mean) varied little across conditions; between 0.55 ± 0.06 (SA), and 0.62 ± 0.06 (AS). Average phase (±2 standard errors of the mean) also varied little; between 0.41 ± 0.02 s (E), and 0.47 ± 0.02 s (O). After Bonferroni correction, no statistically significant differences in gain or phase were found in the presence of specific monochromatic aberrations or in their absence. These results show that the eye's monochromatic aberrations are not necessary for accommodation to track dynamic accommodative stimuli. © 2017 The Authors. Ophthalmic and Physiological Optics published by John Wiley & Sons Ltd on behalf of College of Optometrists.

Spatiotemporal Computations of an Excitable and Plastic Brain: Neuronal Plasticity Leads to Noise-Robust and Noise-Constructive Computations

PubMed Central

Toutounji, Hazem; Pipa, Gordon

2014-01-01

It is a long-established fact that neuronal plasticity occupies the central role in generating neural function and computation. Nevertheless, no unifying account exists of how neurons in a recurrent cortical network learn to compute on temporally and spatially extended stimuli. However, these stimuli constitute the norm, rather than the exception, of the brain's input. Here, we introduce a geometric theory of learning spatiotemporal computations through neuronal plasticity. To that end, we rigorously formulate the problem of neural representations as a relation in space between stimulus-induced neural activity and the asymptotic dynamics of excitable cortical networks. Backed up by computer simulations and numerical analysis, we show that two canonical and widely spread forms of neuronal plasticity, that is, spike-timing-dependent synaptic plasticity and intrinsic plasticity, are both necessary for creating neural representations, such that these computations become realizable. Interestingly, the effects of these forms of plasticity on the emerging neural code relate to properties necessary for both combating and utilizing noise. The neural dynamics also exhibits features of the most likely stimulus in the network's spontaneous activity. These properties of the spatiotemporal neural code resulting from plasticity, having their grounding in nature, further consolidate the biological relevance of our findings. PMID:24651447

Holocene forest dynamics in central and western Mediterranean: periodicity, spatio-temporal patterns and climate influence.

PubMed

Di Rita, Federico; Fletcher, William J; Aranbarri, Josu; Margaritelli, Giulia; Lirer, Fabrizio; Magri, Donatella

2018-06-12

It is well-known that the Holocene exhibits a millennial-scale climate variability. However, its periodicity, spatio-temporal patterns and underlying processes are not fully deciphered yet. Here we focus on the central and western Mediterranean. We show that recurrent forest declines from the Gulf of Gaeta (central Tyrrhenian Sea) reveal a 1860-yr periodicity, consistent with a ca. 1800-yr climate fluctuation induced by large-scale changes in climate modes, linked to solar activity and/or AMOC intensity. We show that recurrent forest declines and dry events are also recorded in several pollen and palaeohydrological proxy-records in the south-central Mediterranean. We found coeval events also in several palaeohydrological records from the south-western Mediterranean, which however show generally wet climate conditions, indicating a spatio-temporal hydrological pattern opposite to the south-central Mediterranean and suggesting that different expressions of climate modes occurred in the two regions at the same time. We propose that these opposite hydroclimate regimes point to a complex interplay of the prevailing or predominant phases of NAO-like circulation, East Atlantic pattern, and extension and location of the North African anticyclone. At a larger geographical scale, displacements of the ITCZ, modulated by solar activity and/or AMOC intensity, may have also indirectly influenced the observed pattern.

Control of cell interaction using quasi-monochromatic light with varying spatiotemporal coherence

NASA Astrophysics Data System (ADS)

Budagovsky, A. V.; Maslova, M. V.; Budagovskaya, O. N.; Budagovsky, I. A.

2017-02-01

By the example of plants, fungi and bacteria, we consider the possibility of controlling the interaction of cells, being in competitive, antagonistic, or parasitic relations. For this aim we used short-time irradiation (a few seconds or minutes) with the red (633 nm) quasi-monochromatic light having different spatiotemporal coherence. It is shown that the functional activity is mostly increased in the cells whose size does not exceed the coherence length and the correlation radius of the light field. Thus, in the case of cells essentially differing in size, it is possible to increase the activity of smaller cells, avoiding the stimulation of larger ones. For example, the radiation having relatively low coherence (Lcoh, rcor <= 10 μm) facilitates mainly the damage of large-size plant cells by pathogen fungi, while the exposure to light with less statistical regularity (Lcoh = 4 μm, rcor = 5 μm) inhibits the growth of the Fusarium microcera fungus, infected by the bacterium of the Pseudomonas species. The quasi-monochromatic radiation with sufficiently high spatiotemporal coherence stimulated all interacting species (bacteria, fungi, plants). In the considered biocenosis, the equilibrium was shifted towards the favour of organisms having the highest rate of cell division or the ones better using their adaptation potential.

Photochemical mechanisms of light-triggered release from nanocarriers

PubMed Central

Fomina, Nadezda; Sankaranarayanan, Jagadis; Almutairi, Adah

2012-01-01

Over the last three decades, a handful of photochemical mechanisms have been applied to a large number of nanoscale assemblies that encapsulate a payload to afford spatio-temporal and remote control over activity of the encapsulated payload. Many of these systems are designed with an eye towards biomedical applications, as spatio-temporal and remote control of bioactivity would advance research and clinical practice. This review covers five underlying photochemical mechanisms that govern the activity of the majority of photoresponsive nanocarriers: 1. photo driven isomerization and oxidation, 2. surface plasmon absorption and photothermal effects, 3. photo driven hydrophobicity changes, 4. photo driven polymer backbone fragmentation and 5. photo driven de-crosslinking. The ways in which these mechanisms have been incorporated into nanocarriers and how they affect release is detailed, as well as the advantages and disadvantages of each system. PMID:22386560

Arabidopsis roots and shoots show distinct temporal adaptation patterns toward nitrogen starvation.

PubMed

Krapp, Anne; Berthomé, Richard; Orsel, Mathilde; Mercey-Boutet, Stéphanie; Yu, Agnes; Castaings, Loren; Elftieh, Samira; Major, Hilary; Renou, Jean-Pierre; Daniel-Vedele, Françoise

2011-11-01

Nitrogen (N) is an essential macronutrient for plants. N levels in soil vary widely, and plants have developed strategies to cope with N deficiency. However, the regulation of these adaptive responses and the coordinating signals that underlie them are still poorly understood. The aim of this study was to characterize N starvation in adult Arabidopsis (Arabidopsis thaliana) plants in a spatiotemporal manner by an integrative, multilevel global approach analyzing growth, metabolites, enzyme activities, and transcript levels. We determined that the remobilization of N and carbon compounds to the growing roots occurred long before the internal N stores became depleted. A global metabolite analysis by gas chromatography-mass spectrometry revealed organ-specific differences in the metabolic adaptation to complete N starvation, for example, for several tricarboxylic acid cycle intermediates, but also for carbohydrates, secondary products, and phosphate. The activities of central N metabolism enzymes and the capacity for nitrate uptake adapted to N starvation by favoring N remobilization and by increasing the high-affinity nitrate uptake capacity after long-term starvation. Changes in the transcriptome confirmed earlier studies and added a new dimension by revealing specific spatiotemporal patterns and several unknown N starvation-regulated genes, including new predicted small RNA genes. No global correlation between metabolites, enzyme activities, and transcripts was evident. However, this multilevel spatiotemporal global study revealed numerous new patterns of adaptation mechanisms to N starvation. In the context of a sustainable agriculture, this work will give new insight for the production of crops with increased N use efficiency.

The Link between Microbial Diversity and Nitrogen Cycling in Marine Sediments Is Modulated by Macrofaunal Bioturbation.

PubMed

Yazdani Foshtomi, Maryam; Braeckman, Ulrike; Derycke, Sofie; Sapp, Melanie; Van Gansbeke, Dirk; Sabbe, Koen; Willems, Anne; Vincx, Magda; Vanaverbeke, Jan

2015-01-01

The marine benthic nitrogen cycle is affected by both the presence and activity of macrofauna and the diversity of N-cycling microbes. However, integrated research simultaneously investigating macrofauna, microbes and N-cycling is lacking. We investigated spatio-temporal patterns in microbial community composition and diversity, macrofaunal abundance and their sediment reworking activity, and N-cycling in seven subtidal stations in the Southern North Sea. Our results indicated that bacteria (total and β-AOB) showed more spatio-temporal variation than archaea (total and AOA) as sedimentation of organic matter and the subsequent changes in the environment had a stronger impact on their community composition and diversity indices in our study area. However, spatio-temporal patterns of total bacterial and β-AOB communities were different and related to the availability of ammonium for the autotrophic β-AOB. Highest bacterial richness and diversity were observed in June at the timing of the phytoplankton bloom deposition, while richness of β-AOB as well as AOA peaked in September. Total archaeal community showed no temporal variation in diversity indices. Distance based linear models revealed that, independent from the effect of grain size and the quality and quantity of sediment organic matter, nitrification and N-mineralization were affected by respectively the diversity of metabolically active β-AOB and AOA, and the total bacteria, near the sediment-water interface. Separate models demonstrated a significant and independent effect of macrofaunal activities on community composition and richness of total bacteria, and diversity indices of metabolically active AOA. Diversity of β-AOB was significantly affected by macrofaunal abundance. Our results support the link between microbial biodiversity and ecosystem functioning in marine sediments, and provided broad correlative support for the hypothesis that this relationship is modulated by macrofaunal activity. We hypothesized that the latter effect can be explained by their bioturbating and bio-irrigating activities, increasing the spatial complexity of the biogeochemical environment.

Temporally diverse firing patterns in olfactory receptor neurons underlie spatiotemporal neural codes for odors

PubMed Central

Raman, Baranidharan; Joseph, Joby; Tang, Jeff; Stopfer, Mark

2010-01-01

Odorants are represented as spatiotemporal patterns of spikes in neurons of the antennal lobe (AL, insects) and olfactory bulb (OB, vertebrates). These response patterns have been thought to arise primarily from interactions within the AL/OB, an idea supported, in part, by the assumption that olfactory receptor neurons (ORNs) respond to odorants with simple firing patterns. However, activating the AL directly with simple pulses of current evoked responses in AL neurons that were much less diverse, complex, and enduring than responses elicited by odorants. Similarly, models of the AL driven by simplistic inputs generated relatively simple output. How then are dynamic neural codes for odors generated? Consistent with recent results from several other species, our recordings from locust ORNs showed a great diversity of temporal structure. Further, we found that, viewed as a population, many response features of ORNs were remarkably similar to those observed within the AL. Using a set of computational models constrained by our electrophysiological recordings, we found that the temporal heterogeneity of responses of ORNs critically underlies the generation of spatiotemporal odor codes in the AL. A test then performed in vivo confirmed that, given temporally homogeneous input, the AL cannot create diverse spatiotemporal patterns on its own; however, given temporally heterogeneous input, the AL generated realistic firing patterns. Finally, given the temporally structured input provided by ORNs, we clarified several separate, additional contributions of the AL to olfactory information processing. Thus, our results demonstrate the origin and subsequent reformatting of spatiotemporal neural codes for odors. PMID:20147528

Spatiotemporal characterization of mTOR kinase activity following kainic acid induced status epilepticus and analysis of rat brain response to chronic rapamycin treatment.

PubMed

Macias, Matylda; Blazejczyk, Magdalena; Kazmierska, Paulina; Caban, Bartosz; Skalecka, Agnieszka; Tarkowski, Bartosz; Rodo, Anna; Konopacki, Jan; Jaworski, Jacek

2013-01-01

Mammalian target of rapamycin (mTOR) is a protein kinase that senses nutrient availability, trophic factors support, cellular energy level, cellular stress, and neurotransmitters and adjusts cellular metabolism accordingly. Adequate mTOR activity is needed for development as well as proper physiology of mature neurons. Consequently, changes in mTOR activity are often observed in neuropathology. Recently, several groups reported that seizures increase mammalian target of rapamycin (mTOR) kinase activity, and such increased activity in genetic models can contribute to spontaneous seizures. However, the current knowledge about the spatiotemporal pattern of mTOR activation induced by proconvulsive agents is rather rudimentary. Also consequences of insufficient mTOR activity on a status epilepticus are poorly understood. Here, we systematically investigated these two issues. We showed that mTOR signaling was activated by kainic acid (KA)-induced status epilepticus through several brain areas, including the hippocampus and cortex as well as revealed two waves of mTOR activation: an early wave (2 h) that occurs in neurons and a late wave that predominantly occurs in astrocytes. Unexpectedly, we found that pretreatment with rapamycin, a potent mTOR inhibitor, gradually (i) sensitized animals to KA treatment and (ii) induced gross anatomical changes in the brain.

Spatiotemporal Characterization of mTOR Kinase Activity Following Kainic Acid Induced Status Epilepticus and Analysis of Rat Brain Response to Chronic Rapamycin Treatment

PubMed Central

Macias, Matylda; Blazejczyk, Magdalena; Kazmierska, Paulina; Caban, Bartosz; Skalecka, Agnieszka; Tarkowski, Bartosz; Rodo, Anna; Konopacki, Jan; Jaworski, Jacek

2013-01-01

Mammalian target of rapamycin (mTOR) is a protein kinase that senses nutrient availability, trophic factors support, cellular energy level, cellular stress, and neurotransmitters and adjusts cellular metabolism accordingly. Adequate mTOR activity is needed for development as well as proper physiology of mature neurons. Consequently, changes in mTOR activity are often observed in neuropathology. Recently, several groups reported that seizures increase mammalian target of rapamycin (mTOR) kinase activity, and such increased activity in genetic models can contribute to spontaneous seizures. However, the current knowledge about the spatiotemporal pattern of mTOR activation induced by proconvulsive agents is rather rudimentary. Also consequences of insufficient mTOR activity on a status epilepticus are poorly understood. Here, we systematically investigated these two issues. We showed that mTOR signaling was activated by kainic acid (KA)-induced status epilepticus through several brain areas, including the hippocampus and cortex as well as revealed two waves of mTOR activation: an early wave (2 h) that occurs in neurons and a late wave that predominantly occurs in astrocytes. Unexpectedly, we found that pretreatment with rapamycin, a potent mTOR inhibitor, gradually (i) sensitized animals to KA treatment and (ii) induced gross anatomical changes in the brain. PMID:23724051

Comparison of wavefront aberrations under cycloplegic, scotopic and photopic conditions using WaveScan.

PubMed

Fan, Rong; He, Tao; Qiu, Yan; Di, Yu-Lan; Xu, Su-yun; Li, Yao-yu

2012-01-01

To evaluate the differences of wavefront aberrations under cycloplegic, scotopic and photopic conditions. A total of 174 eyes of 105 patients were measured using the wavefront sensor (WaveScan® 3.62) under different pupil conditions: cycloplegic 8.58 ± 0.54 mm (6.4 mm - 9.5 mm), scotopic 7.53 ± 0.69 mm (5.7 mm - 9.1 mm) and photopic 6.08 ± 1.14 mm (4.1 mm - 8.8 mm). The pupil diameter, standard Zernike coefficients, root mean square of higher-order aberrations and dominant aberrations were compared between cycloplegic and scotopic conditions, and between scotopic and photopic conditions. The pupil diameter was 7.53 ± 0.69 mm under the scotopic condition, which reached the requirement of about 6.5 mm optical zone design in the wavefront-guided surgery and prevented measurement error due to the pupil centroid shift caused by mydriatics. Pharmacological pupil dilation induced increase of standard Zernike coefficients Z(3)(-3), Z(4)(0) and Z(5)(-5). The higher-order aberrations, third-order aberration, fourth-order aberration, fifth-order aberration, sixth-order aberration, and spherical aberration increased statistically significantly, compared to the scotopic condition (P<0.010). When the scotopic condition shifted to the photopic condition, the standard Zernike coefficients Z(4)(0), Z(4)(2), Z(6)(-4), Z(6)(-2), Z(6)(2) decreased and all the higher-order aberrations decreased statistically significantly (P<0.010), demonstrating that accommodative miosis can significantly improve vision under the photopic condition. Under the three conditions, the vertical coma aberration appears the most frequently within the dominant aberrations without significant effect by pupil size variance, and the proportion of spherical aberrations decreased with the decrease of the pupil size. The wavefront aberrations are significantly different under cycloplegic, scotopic and photopic conditions. Using the wavefront sensor (VISX WaveScan) to measure scotopic wavefront aberrations is feasible for the wavefront-guided refractive surgery.

Distinct spatiotemporal activity in principal neurons of the mouse olfactory bulb in anesthetized and awake states

PubMed Central

Blauvelt, David G.; Sato, Tomokazu F.; Wienisch, Martin; Murthy, Venkatesh N.

2013-01-01

The acquisition of olfactory information and its early processing in mammals are modulated by brain states through sniffing behavior and neural feedback. We imaged the spatiotemporal pattern of odor-evoked activity in a population of output neurons (mitral/tufted cells, MTCs) in the olfactory bulb (OB) of head-restrained mice expressing a genetically-encoded calcium indicator. The temporal dynamics of MTC population activity were relatively simple in anesthetized animals, but were highly variable in awake animals. However, the apparently irregular activity in awake animals could be predicted well using sniff timing measured externally, or inferred through fluctuations in the global responses of MTC population even without explicit knowledge of sniff times. The overall spatial pattern of activity was conserved across states, but odor responses had a diffuse spatial component in anesthetized mice that was less prominent during wakefulness. Multi-photon microscopy indicated that MTC lateral dendrites were the likely source of spatially disperse responses in the anesthetized animal. Our data demonstrate that the temporal and spatial dynamics of MTCs can be significantly modulated by behavioral state, and that the ensemble activity of MTCs can provide information about sniff timing to downstream circuits to help decode odor responses. PMID:23543674

Baseline study of the spatio-temporal patterns of reef fish assemblages prior to a major mining project in New Caledonia (South Pacific).

PubMed

Chabanet, Pascale; Guillemot, Nicolas; Kulbicki, Michel; Vigliola, Laurent; Sarramegna, Sébastien

2010-01-01

From 2008 onwards, the coral reefs of Koné (New Caledonia) will be subjected to a major anthropogenic perturbation linked to development of a nickel mine. Dredging and sediment runoff may directly damage the reef environment whereas job creation should generate a large demographic increase and thus a rise in fishing activities. This study analyzed reef fish assemblages between 2002 and 2007 with a focus on spatio-temporal variability. Our results indicate strong spatial structure of fish assemblages through time. Total species richness, density and biomass were highly variable between years but temporal variations were consistent among biotopes. A remarkable spatio-temporal stability was observed for trophic (mean 4.6% piscivores, 53.1% carnivores, 30.8% herbivores and 11.4% planktivores) and home range structures of species abundance contributions. These results are discussed and compared with others sites of the South Pacific. For monitoring perspectives, some indicators related to expected disturbances are proposed. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

Spatio-temporal dynamics of a fish spawning aggregation and its fishery in the Gulf of California

PubMed Central

Erisman, Brad; Aburto-Oropeza, Octavio; Gonzalez-Abraham, Charlotte; Mascareñas-Osorio, Ismael; Moreno-Báez, Marcia; Hastings, Philip A.

2012-01-01

We engaged in cooperative research with fishers and stakeholders to characterize the fine-scale, spatio-temporal characteristics of spawning behavior in an aggregating marine fish (Cynoscion othonopterus: Sciaenidae) and coincident activities of its commercial fishery in the Upper Gulf of California. Approximately 1.5–1.8 million fish are harvested annually from spawning aggregations of C. othonopterus during 21–25 days of fishing and within an area of 1,149 km2 of a biosphere reserve. Spawning and fishing are synchronized on a semi-lunar cycle, with peaks in both occurring 5 to 2 days before the new and full moon, and fishing intensity and catch are highest at the spawning grounds within a no-take reserve. Results of this study demonstrate the benefits of combining GPS data loggers, fisheries data, biological surveys, and cooperative research with fishers to produce spatio-temporally explicit information relevant to the science and management of fish spawning aggregations and the spatial planning of marine reserves. PMID:22359736

The evolution of meaning: spatio-temporal dynamics of visual object recognition.

PubMed

Clarke, Alex; Taylor, Kirsten I; Tyler, Lorraine K

2011-08-01

Research on the spatio-temporal dynamics of visual object recognition suggests a recurrent, interactive model whereby an initial feedforward sweep through the ventral stream to prefrontal cortex is followed by recurrent interactions. However, critical questions remain regarding the factors that mediate the degree of recurrent interactions necessary for meaningful object recognition. The novel prediction we test here is that recurrent interactivity is driven by increasing semantic integration demands as defined by the complexity of semantic information required by the task and driven by the stimuli. To test this prediction, we recorded magnetoencephalography data while participants named living and nonliving objects during two naming tasks. We found that the spatio-temporal dynamics of neural activity were modulated by the level of semantic integration required. Specifically, source reconstructed time courses and phase synchronization measures showed increased recurrent interactions as a function of semantic integration demands. These findings demonstrate that the cortical dynamics of object processing are modulated by the complexity of semantic information required from the visual input.

Spatiotemporal earthquake clusters along the North Anatolian fault zone offshore Istanbul

USGS Publications Warehouse

Bulut, Fatih; Ellsworth, William L.; Bohnhoff, Marco; Aktar, Mustafa; Dresen, Georg

2011-01-01

We investigate earthquakes with similar waveforms in order to characterize spatiotemporal microseismicity clusters within the North Anatolian fault zone (NAFZ) in northwest Turkey along the transition between the 1999 ??zmit rupture zone and the Marmara Sea seismic gap. Earthquakes within distinct activity clusters are relocated with cross-correlation derived relative travel times using the double difference method. The spatiotemporal distribution of micro earthquakes within individual clusters is resolved with relative location accuracy comparable to or better than the source size. High-precision relative hypocenters define the geometry of individual fault patches, permitting a better understanding of fault kinematics and their role in local-scale seismotectonics along the region of interest. Temporal seismic sequences observed in the eastern Sea of Marmara region suggest progressive failure of mostly nonoverlapping areas on adjacent fault patches and systematic migration of microearthquakes within clusters during the progressive failure of neighboring fault patches. The temporal distributions of magnitudes as well as the number of events follow swarmlike behavior rather than a mainshock/aftershock pattern.

Spatiotemporal source tuning filter bank for multiclass EEG based brain computer interfaces.

PubMed

Acharya, Soumyadipta; Mollazadeh, Moshen; Murari, Kartikeya; Thakor, Nitish

2006-01-01

Non invasive brain-computer interfaces (BCI) allow people to communicate by modulating features of their electroencephalogram (EEG). Spatiotemporal filtering has a vital role in multi-class, EEG based BCI. In this study, we used a novel combination of principle component analysis, independent component analysis and dipole source localization to design a spatiotemporal multiple source tuning (SPAMSORT) filter bank, each channel of which was tuned to the activity of an underlying dipole source. Changes in the event-related spectral perturbation (ERSP) were measured and used to train a linear support vector machine to classify between four classes of motor imagery tasks (left hand, right hand, foot and tongue) for one subject. ERSP values were significantly (p<0.01) different across tasks and better (p<0.01) than conventional spatial filtering methods (large Laplacian and common average reference). Classification resulted in an average accuracy of 82.5%. This approach could lead to promising BCI applications such as control of a prosthesis with multiple degrees of freedom.

Aberration of a negative ion beam caused by space charge effect.

PubMed

Miyamoto, K; Wada, S; Hatayama, A

2010-02-01

Aberrations are inevitable when the charged particle beams are extracted, accelerated, transmitted, and focused with electrostatic and magnetic fields. In this study, we investigate the aberration of a negative ion accelerator for a neutral beam injector theoretically, especially the spherical aberration caused by the negative ion beam expansion due to the space charge effect. The negative ion current density profiles with the spherical aberration are compared with those without the spherical aberration. It is found that the negative ion current density profiles in a log scale are tailed due to the spherical aberration.

Analysis for maladjustment properties of passive confocal unstable resonator by using Hartmann-Shack wavefront sensor

NASA Astrophysics Data System (ADS)

Zhang, Xiang; Xiang, Anping

2007-12-01

The effect of intracavity aberration perturbation on output mode structure properties of passive confocal unstable resonator is been experimentally researched by adopting Hartmann-Shack method on the basis of numerical simulation. The results show that intracavity tilt aberration affects the outcoupled intensity distribution, but only a small intracavity tilt perturbation will not obviously augment the high-order aberrations of beam phase properties. The tilt aberration, coma aberration and astigmatism will all be brought, and also tilt aberration is the main component when intracavity mirrors have a vertical movement along the direction of optic axis. When adaptive optical elements such as deformable mirrors are adopted for intracavity aberration correction, the correction for tilt aberration should be considered at first.

Mask-induced aberration in EUV lithography

NASA Astrophysics Data System (ADS)

Nakajima, Yumi; Sato, Takashi; Inanami, Ryoichi; Nakasugi, Tetsuro; Higashiki, Tatsuhiko

2009-04-01

We estimated aberrations using Zernike sensitivity analysis. We found the difference of the tolerated aberration with line direction for illumination. The tolerated aberration of perpendicular line for illumination is much smaller than that of parallel line. We consider this difference to be attributable to the mask 3D effect. We call it mask-induced aberration. In the case of the perpendicular line for illumination, there was a difference in CD between right line and left line without aberration. In this report, we discuss the possibility of pattern formation in NA 0.25 generation EUV lithography tool. In perpendicular pattern for EUV light, the dominant part of aberration is mask-induced aberration. In EUV lithography, pattern correction based on the mask topography effect will be more important.

Aberrant dopamine D2-like receptor function in a rodent model of schizophrenia.

PubMed

Perez, Stephanie M; Lodge, Daniel J

2012-11-01

Based on the observation that antipsychotic medications display antagonist properties at dopamine D2-like receptors, aberrant dopamine signaling has been proposed to underlie psychosis in patients with schizophrenia. Thus, it is not surprising that considerable research has been devoted to understanding the mechanisms involved in the antipsychotic action of these compounds. It is important to note that the majority of these studies have been performed in "normal" experimental animals. Given that these animals do not possess the aberrant neuronal information processing typically associated with schizophrenia, the aim of the current study was to examine the dopamine D2 receptor system in a rodent model of schizophrenia. Here, we demonstrate that methylazoxymethanol acetate (MAM)-treated rats display an enhanced effect of quinpirole on dopamine neuron activity and an aberrant locomotor response to D2-like receptor activation, suggesting changes in postsynaptic D2-like receptor function. To better understand the mechanisms underlying the enhanced response to D2-like ligands in MAM-treated rats, we examined the expression of D2, D3, and dopamine transporter mRNA in the nucleus accumbens and ventral tegmental area by quantitative reverse transcription-polymerase chain reaction. MAM-treated rats displayed a significant increase in dopamine D3 receptor mRNA expression in the nucleus accumbens with no significant changes in the expression of the D2 receptor. Taken together, these data demonstrate robust alterations in dopamine D2-like receptor function in a rodent model of schizophrenia and provide evidence that preclinical studies examining the mechanisms of antipsychotic drug action should be performed in animal models that mirror aspects of the abnormal neuronal transmission thought to underlie symptoms of schizophrenia.

In vivo radioprotection by alpha-TMG: preliminary studies.

PubMed

Satyamitra, M; Devi, P U; Murase, H; Kagiya, V T

2001-08-08

alpha-TMG is a novel water-soluble derivative of Vitamin E that has shown excellent antioxidant activity. The parent compound has demonstrated protection against radiation induced chromosomal damage in vivo. Hence, the preliminary experiments to determine the radioprotective activity of alpha-TMG were carried out in adult Swiss albino mice. Acute toxicity of the drug was studied taking 24h, 72 h and 30 day mortality after a single intraperitoneal injection of 500-2000 mg/kg body weight of the drug. The drug LD(50) for 24h and 72 h/30 day survival were found to be 1120 and 1000 mg/kg body weight, respectively. The optimum time of drug administration and drug dose-dependent effect on in vivo radiation protection of bone marrow chromosomes was studied in mice. Injection of 600 mg/kg of the drug 15 min before or within 5, 15 or 30min after 3Gy whole body gamma radiation resulted in a significant decrease in the aberrant metaphases percent at 24h post-irradiation; the maximum effect was seen when the drug was given immediately after irradiation. Injection of 200-800 mg/kg TMG within 5 min of irradiation with 3 Gy produced a significant dose-dependent reduction in the radiation induced percent aberrant metaphases and in the frequency of micronucleated erythrocytes at 24h after exposure, with a corresponding decrease in the different types of aberrations. The optimum dose for protection without drug toxicity was 600 mg/kg body weight. At this dose, TMG produced 70 and >60% reduction in the radiation induced percent aberrant metaphases and micronucleated erythrocytes, respectively. The high water solubility and effectiveness when administered post-irradiation favor TMG as a likely candidate for protection in case of accidental exposures.

Negative symptoms in schizophrenia are associated with aberrant striato-cortical connectivity in a rewarded perceptual decision-making task.

PubMed

Reckless, Greg E; Andreassen, Ole A; Server, Andres; Østefjells, Tiril; Jensen, Jimmy

2015-01-01

Negative symptoms in schizophrenia have been associated with structural and functional changes in the prefrontal cortex. They often persist after treatment with antipsychotic medication which targets, in particular, the ventral striatum (VS). As schizophrenia has been suggested to arise from dysfunctional connectivity between neural networks, it is possible that residual aberrant striato-cortical connectivity in medicated patients plays a role in enduring negative symptomology. The present study examined the relationship between striato-cortical connectivity and negative symptoms in medicated schizophrenia patients. We manipulated motivation in a perceptual decision-making task during functional magnetic resonance imaging. Comparing healthy controls (n = 21) and medicated patients with schizophrenia (n = 18) we investigated how motivation-mediated changes in VS activation affected functional connectivity with the frontal cortex, and how changes in connectivity strength from the neutral to motivated condition related to negative symptom severity. A pattern of aberrant striato-cortical connectivity was observed in the presence of intact VS, but altered left inferior frontal gyrus (IFG) motivation-mediated activation in patients. The more severe the patient's negative symptoms, the less the connectivity strength between the right VS and left IFG changed from the neutral to the motivated condition. Despite aberrant striato-cortical connectivity and altered recruitment of the left IFG among patients, both patients and healthy controls adopted a more liberal response strategy in the motivated compared to the neutral condition. The present findings suggest that there is a link between dysfunctional striato-cortical connectivity and negative symptom severity, and offer a possible explanation as to why negative symptoms persist after treatment with antipsychotics.

Tyrosine kinase receptor c-ros-oncogene 1 inhibition alleviates aberrant bone formation of TWIST-1 haploinsufficient calvarial cells from Saethre-Chotzen syndrome patients.

PubMed

Camp, Esther; Anderson, Peter J; Zannettino, Andrew C W; Glackin, Carlotta A; Gronthos, Stan

2018-09-01

Saethre-Chotzen syndrome (SCS), associated with TWIST-1 mutations, is characterized by premature fusion of cranial sutures. TWIST-1 haploinsufficiency, leads to alterations in suture mesenchyme cellular gene expression patterns, resulting in aberrant osteogenesis and craniosynostosis. We analyzed the expression of the TWIST-1 target, Tyrosine kinase receptor c-ros-oncogene 1 (C-ROS-1) in TWIST-1 haploinsufficient calvarial cells derived from SCS patients and calvaria of Twist-1 del/+ mutant mice and found it to be highly expressed when compared to TWIST-1 wild-type controls. Knock-down of C-ROS-1 expression in TWIST-1 haploinsufficient calvarial cells derived from SCS patients was associated with decreased capacity for osteogenic differentiation in vitro. Furthermore, treatment of human SCS calvarial cells with the tyrosine kinase chemical inhibitor, Crizotinib, resulted in reduced C-ROS-1 activity and the osteogenic potential of human SCS calvarial cells with minor effects on cell viability or proliferation. Cultured human SCS calvarial cells treated with Crizotinib exhibited a dose-dependent decrease in alkaline phosphatase activity and mineral deposition, with an associated decrease in expression levels of Runt-related transcription factor 2 and OSTEOPONTIN, with reduced PI3K/Akt signalling in vitro. Furthermore, Crizotinib treatment resulted in reduced BMP-2 mediated bone formation potential of whole Twist-1 del/+ mutant mouse calvaria organotypic cultures. Collectively, these results suggest that C-ROS-1 promotes osteogenic differentiation of TWIST-1 haploinsufficient calvarial osteogenic progenitor cells. Furthermore, the aberrant osteogenic potential of these cells is inhibited by the reduction of C-ROS-1. Therefore, targeting C-ROS-1 with a pharmacological agent, such as Crizotinib, may serve as a novel therapeutic strategy to alleviate craniosynostosis associated with aberrant TWIST-1 function. © 2018 Wiley Periodicals, Inc.

How and why do toxic conformers of aberrant proteins accumulate during ageing?

PubMed

Josefson, Rebecca; Andersson, Rebecca; Nyström, Thomas

2017-07-15

Ageing can be defined as a gradual decline in cellular and physical functions accompanied by an increased sensitivity to the environment and risk of death. The increased risk of mortality is causally connected to a gradual, intracellular accumulation of so-called ageing factors, of which damaged and aggregated proteins are believed to be one. Such aggregated proteins also contribute to several age-related neurodegenerative disorders e.g. Alzheimer's, Parkinson's, and Huntington's diseases, highlighting the importance of protein quality control (PQC) in ageing and its associated diseases. PQC consists of two interrelated systems: the temporal control system aimed at refolding, repairing, and/or removing aberrant proteins and their aggregates and the spatial control system aimed at harnessing the potential toxicity of aberrant proteins by sequestering them at specific cellular locations. The accumulation of toxic conformers of aberrant proteins during ageing is often declared to be a consequence of an incapacitated temporal PQC system-i.e. a gradual decline in the activity of chaperones and proteases. Here, we review the current knowledge on PQC in relation to ageing and highlight that the breakdown of both temporal and spatial PQC may contribute to ageing and thus comprise potential targets for therapeutic interventions of the ageing process. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Aberration control in adaptive optics: a numerical study of arbitrarily deformable liquid lenses.

PubMed

Lima, N C; Mishra, K; Mugele, F

2017-03-20

By means of numerical simulations, using a computational fluid dynamics software together with an optical ray tracing analysis platform, we show that we can tune various optical aberrations by electrically manipulating the shape of liquid lenses using one hundred individually addressable electrodes. To demonstrate the flexibility of our design, we define electrode patterns based on specific Zernike modes and show that aspherical, cylindrical and decentered shapes of liquid lenses can be produced. Using different voltages, we evaluate the tuning range of spherical aberration (Z11), astigmatism (Z5 and Z6) and coma (Z7), while a hydrostatic pressure is applied to control the average curvature of a microlens with a diameter of 1mm. Upon activating all electrodes simultaneously spherical aberrations of 0.15 waves at a pressure of 30Pa can be suppressed almost completely for the highest voltages applied. For astigmatic and comatic patterns, the values of Z5, Z6 and Z7 increase monotonically with the voltage reaching values up to 0.06, 0.06 and 0.2 waves, respectively. Spot diagrams, wavefront maps and modulation transfer function are reported to quantify the optical performance of each lens. Crosstalk and independence of tunability are discussed in the context of possible applications of the approach for general wavefront shaping.

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

Brandriff, B.F.; Gordon, L.A.

Human reproductive wastage is known to be a common event. One major cause of embryonic and fetal losses is chromosomal aberrations, identified by karyotyping spontaneous abortion material and in vitro fertilized human embryos. Karyotyping of human gametes has made it possible to document types and frequencies of chromosomal aberrations directly in eggs and sperm themselves. Our studies with human sperm from normal, healthy men support the view that chromosome-specific aneuploidy does in fact occur, and that frequencies of structural chromosomal aberrations appear to be person specific and stable over time. The types of structural aberrations identified suggest that normal humanmore » spermiogenesis may be vulnerable to breakage events or precursor lesions leading to such breakage events. After entry into egg cytoplasm and preceding the formation of first-cleavage mitotic chromosomes, the male as well as the female genome replicate their DNA in a pattern qualitatively similar to that in somatic cells. However, at present it is not known what relationship exists between spontaneous chromosome breaks seen at first cleavage and DNA replication activities. Limited data on survivors of radiotherapy lend support to the view that long-term effects on sperm chromosomal integrity can be identified. Studies on sperm cytogenetics thus have the potential for identifying adverse environmental effects on human spermatogenesis as monitored by this well-defined endpoint. 32 refs., 2 figs., 1 tab.« less

Hyperforin Exhibits Antigenotoxic Activity on Human and Bacterial Cells.

PubMed

Imreova, Petronela; Feruszova, Jana; Kyzek, Stanislav; Bodnarova, Kristina; Zduriencikova, Martina; Kozics, Katarina; Mucaji, Pavel; Galova, Eliska; Sevcovicova, Andrea; Miadokova, Eva; Chalupa, Ivan

2017-01-21

Hyperforin (HF), a substance that accumulates in the leaves and flowers of Hypericum perforatum L. (St. John's wort), consists of a phloroglucinol skeleton with lipophilic isoprene chains. HF exhibits several medicinal properties and is mainly used as an antidepressant. So far, the antigenotoxicity of HF has not been investigated at the level of primary genetic damage, gene mutations, and chromosome aberrations, simultaneously. The present work is designed to investigate the potential antigenotoxic effects of HF using three different experimental test systems. The antigenotoxic effect of HF leading to the decrease of primary/transient promutagenic genetic changes was detected by the alkaline comet assay on human lymphocytes. The HF antimutagenic effect leading to the reduction of gene mutations was assessed using the Ames test on the standard Salmonella typhimurium (TA97, TA98, and TA100) bacterial strains, and the anticlastogenic effect of HF leading to the reduction of chromosome aberrations was evaluated by the in vitro mammalian chromosome aberration test on the human tumor cell line HepG2 and the non-carcinogenic cell line VH10. Our findings provided evidence that HF showed antigenotoxic effects towards oxidative mutagen zeocin in the comet assay and diagnostic mutagen (4-nitroquinoline-1-oxide) in the Ames test. Moreover, HF exhibited an anticlastogenic effect towards benzo(a)pyrene and cisplatin in the chromosome aberration test.

Endogenous oncogenic Nras mutation promotes aberrant GM-CSF signaling in granulocytic/monocytic precursors in a murine model of chronic myelomonocytic leukemia.

PubMed

Wang, Jinyong; Liu, Yangang; Li, Zeyang; Du, Juan; Ryu, Myung-Jeom; Taylor, Philip R; Fleming, Mark D; Young, Ken H; Pitot, Henry; Zhang, Jing

2010-12-23

Oncogenic NRAS mutations are frequently identified in myeloid diseases involving monocyte lineage. However, its role in the genesis of these diseases remains elusive. We report a mouse bone marrow transplantation model harboring an oncogenic G12D mutation in the Nras locus. Approximately 95% of recipient mice develop a myeloproliferative disease resembling the myeloproliferative variant of chronic myelomonocytic leukemia (CMML), with a prolonged latency and acquisition of multiple genetic alterations, including uniparental disomy of oncogenic Nras allele. Based on single-cell profiling of phospho-proteins, a novel population of CMML cells is identified to display aberrant granulocyte-macrophage colony stimulating factor (GM-CSF) signaling in both the extracellular signal-regulated kinase (ERK) 1/2 and signal transducer and activator of transcription 5 (Stat5) pathways. This abnormal signaling is acquired during CMML development. Further study suggests that aberrant Ras/ERK signaling leads to expansion of granulocytic/monocytic precursors, which are highly responsive to GM-CSF. Hyperactivation of Stat5 in CMML cells is mainly through expansion of these precursors rather than up-regulation of surface expression of GM-CSF receptors. Our results provide insights into the aberrant cytokine signaling in oncogenic NRAS-associated myeloid diseases.

Abnormal salience signaling in schizophrenia: The role of integrative beta oscillations.

PubMed

Liddle, Elizabeth B; Price, Darren; Palaniyappan, Lena; Brookes, Matthew J; Robson, Siân E; Hall, Emma L; Morris, Peter G; Liddle, Peter F

2016-04-01

Aberrant salience attribution and cerebral dysconnectivity both have strong evidential support as core dysfunctions in schizophrenia. Aberrant salience arising from an excess of dopamine activity has been implicated in delusions and hallucinations, exaggerating the significance of everyday occurrences and thus leading to perceptual distortions and delusional causal inferences. Meanwhile, abnormalities in key nodes of a salience brain network have been implicated in other characteristic symptoms, including the disorganization and impoverishment of mental activity. A substantial body of literature reports disruption to brain network connectivity in schizophrenia. Electrical oscillations likely play a key role in the coordination of brain activity at spatially remote sites, and evidence implicates beta band oscillations in long-range integrative processes. We used magnetoencephalography and a task designed to disambiguate responses to relevant from irrelevant stimuli to investigate beta oscillations in nodes of a network implicated in salience detection and previously shown to be structurally and functionally abnormal in schizophrenia. Healthy participants, as expected, produced an enhanced beta synchronization to behaviorally relevant, as compared to irrelevant, stimuli, while patients with schizophrenia showed the reverse pattern: a greater beta synchronization in response to irrelevant than to relevant stimuli. These findings not only support both the aberrant salience and disconnectivity hypotheses, but indicate a common mechanism that allows us to integrate them into a single framework for understanding schizophrenia in terms of disrupted recruitment of contextually appropriate brain networks. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

Abnormal salience signaling in schizophrenia: The role of integrative beta oscillations

PubMed Central

Liddle, Elizabeth B.; Price, Darren; Palaniyappan, Lena; Brookes, Matthew J.; Robson, Siân E.; Hall, Emma L.; Morris, Peter G.

2016-01-01

Abstract Aberrant salience attribution and cerebral dysconnectivity both have strong evidential support as core dysfunctions in schizophrenia. Aberrant salience arising from an excess of dopamine activity has been implicated in delusions and hallucinations, exaggerating the significance of everyday occurrences and thus leading to perceptual distortions and delusional causal inferences. Meanwhile, abnormalities in key nodes of a salience brain network have been implicated in other characteristic symptoms, including the disorganization and impoverishment of mental activity. A substantial body of literature reports disruption to brain network connectivity in schizophrenia. Electrical oscillations likely play a key role in the coordination of brain activity at spatially remote sites, and evidence implicates beta band oscillations in long‐range integrative processes. We used magnetoencephalography and a task designed to disambiguate responses to relevant from irrelevant stimuli to investigate beta oscillations in nodes of a network implicated in salience detection and previously shown to be structurally and functionally abnormal in schizophrenia. Healthy participants, as expected, produced an enhanced beta synchronization to behaviorally relevant, as compared to irrelevant, stimuli, while patients with schizophrenia showed the reverse pattern: a greater beta synchronization in response to irrelevant than to relevant stimuli. These findings not only support both the aberrant salience and disconnectivity hypotheses, but indicate a common mechanism that allows us to integrate them into a single framework for understanding schizophrenia in terms of disrupted recruitment of contextually appropriate brain networks. Hum Brain Mapp 37:1361‐1374, 2016. © 2016 Wiley Periodicals, Inc. PMID:26853904

Evaluation of the genotoxicity of extracts of Houttuynia cordata Thunb.

PubMed

Kang, Chang Keun; Hah, Dae Sik; Kim, Chung Hui; Kim, Euikyung; Kim, Jong Shu

2012-01-01

The present study was conducted to evaluate the activity of methanol extracts from Houttuynia cordata Thunb. (HC) in a reverse mutation assay in Salmonella typhimurium, and a chromosome aberration assay in the Chinese hamster ovary (CHO) cell line and to evaluate its effect on the occurrence of polychromatic erythrocytes in mice. In the reverse mutation assay using Salmonella typhimurium TA98, TA100, TA1535, and TA1537 and Escherichia coli WP2urvA(-), methanol extracts of HC (5, 2.5, 1.25, 0.62, or 0.312 mg/plate) did not induce reverse mutations in the presence or absence of an S9 metabolic activation mixture. In the chromosome aberration test using CHO cells, methanol extracts (1.25, 2.5 or 5 μg/ml) caused a few incidences of structural and numerical aberrations, in both of absence or presence of an S9 metabolic activation mixture, but in comparison with the positive control group, these incidences were not significantly increased. In the mouse micronucleus test, no significant increases in the occurrence of micronucleated polychromatic erythrocytes were observed in male ICR mice that were orally administered methanol extracts of HC at doses of 2.0, 1.0, or 0.5 g/kg. From these results, we concluded that the methanol extracts of HC did not induce harmful effects on genes in bacteria, a mammalian cell system or in mouse bone marrow cells. Thus, HC's use for health promotion and/or a sick remedy for humans may be safe.

Epigenetic silencing of the NR4A3 tumor suppressor, by aberrant JAK/STAT signaling, predicts prognosis in gastric cancer

NASA Astrophysics Data System (ADS)

Yeh, Chung-Min; Chang, Liang-Yu; Lin, Shu-Hui; Chou, Jian-Liang; Hsieh, Hsiao-Yen; Zeng, Li-Han; Chuang, Sheng-Yu; Wang, Hsiao-Wen; Dittner, Claudia; Lin, Cheng-Yu; Lin, Jora M. J.; Huang, Yao-Ting; Ng, Enders K. W.; Cheng, Alfred S. L.; Wu, Shu-Fen; Lin, Jiayuh; Yeh, Kun-Tu; Chan, Michael W. Y.

2016-08-01

While aberrant JAK/STAT signaling is crucial to the development of gastric cancer (GC), its effects on epigenetic alterations of its transcriptional targets remains unclear. In this study, by expression microarrays coupled with bioinformatic analyses, we identified a putative STAT3 target gene, NR4A3 that was downregulated in MKN28 GC daughter cells overexpressing a constitutively activated STAT3 mutant (S16), as compared to an empty vector control (C9). Bisulphite pyrosequencing and demethylation treatment showed that NR4A3 was epigenetically silenced by promoter DNA methylation in S16 and other GC cell lines including AGS cells, showing constitutive activation of STAT3. Subsequent experiments revealed that NR4A3 promoter binding by STAT3 might repress its transcription. Long-term depletion of STAT3 derepressed NR4A3 expression, by promoter demethylation, in AGS GC cells. NR4A3 re-expression in GC cell lines sensitized the cells to cisplatin, and inhibited tumor growth in vitro and in vivo, in an animal model. Clinically, GC patients with high NR4A3 methylation, or lower NR4A3 protein expression, had significantly shorter overall survival. Intriguingly, STAT3 activation significantly associated only with NR4A3 methylation in low-stage patient samples. Taken together, aberrant JAK/STAT3 signaling epigenetically silences a potential tumor suppressor, NR4A3, in gastric cancer, plausibly representing a reliable biomarker for gastric cancer prognosis.

Aromatase up-regulation, insulin and raised intracellular oestrogens in men, induce adiposity, metabolic syndrome and prostate disease, via aberrant ER-α and GPER signalling.

PubMed

Williams, Graeme

2012-04-04

For some years now, reduced testosterone levels have been related to obesity, insulin resistance, type 2 diabetes, heart disease, benign prostatic hypertrophy and even prostate cancer--often considered guilty more by association, than actual cause--with little attention paid to the important role of increased intracellular oestrogen, in the pathogenesis of these chronic diseases. In the final stage of the steroidogenic cascade, testosterone is metabolised to oestradiol by P450 aromatase, in the cytoplasm of adipocytes, breast cells, endothelial cells and prostate cells, to increase intracellular oestradiol concentration at the expense of testosterone. It follows therefore, that any compound that up-regulates aromatase, or any molecule that mimics oestrogen, will not only increase the activation of the mainly proliferative, classic ER-α, oestrogen receptors to induce adipogenesis and growth disorders in oestrogen-sensitive tissues, but also activate the recently identified transmembrane G protein-coupled oestrogen receptors (GPER), and deleteriously alter important intracellular signalling sequences, that promote mitogenic growth and endothelial damage. This paper simplifies how stress, xeno-oestrogens, poor dietary choices and reactive toxins up-regulate aromatase to increase intracellular oestradiol production; how oestradiol in combination with leptin and insulin cause insulin resistance and leptin resistance through aberrant serine phosphorylation; how the increased oestradiol, insulin and leptin stimulate rapid, non-genomic G protein-coupled phosphorylation cascades, to increase fat deposition and create the vasoconstrictive, dyslipidemic features of metabolic syndrome; how aberrant GPER signalling induces benign prostatic hypertrophy; and how increased intracellular oestradiol stimulates mitogenic change and tumour-cell activators, to cause prostate cancer. In essence, the up-regulation of aromatase produces increased intracellular oestradiol, increases ER-α activation and increases GPER activation, in combination with insulin, to cause aberrant downstream transduction signaling, and thus induce metabolic syndrome and mitogenic prostate growth. To understand this fact, that raised intracellular oestradiol levels in men, induce and promote obesity, gynecomastia, metabolic syndrome, type two diabetes, benign prostatic hypertrophy and prostate cancer, rather than low testosterone, represents a shift in medical thinking, a new awareness, that will reduce the rising incidence of obesity, metabolic syndrome and prostate disease, and significantly improve the health of men worldwide. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Aberrant Spontaneous and Task-Dependent Functional Connections in the Anxious Brain

PubMed Central

MacNamara, Annmarie; DiGangi, Julia; Phan, K. Luan

2016-01-01

A number of brain regions have been implicated in the anxiety disorders, yet none of these regions in isolation has been distinguished as the sole or discrete site responsible for anxiety disorder pathology. Therefore, the identification of dysfunctional neural networks as represented by alterations in the temporal correlation of blood-oxygen level dependent (BOLD) signal across several brain regions in anxiety disorders has been increasingly pursued in the past decade. Here, we review task-independent (e.g., resting state) and task-induced functional connectivity magnetic resonance imaging (fcMRI) studies in the adult anxiety disorders (including trauma- and stressor-related and obsessive compulsive disorders). The results of this review suggest that anxiety disorder pathophysiology involves aberrant connectivity between amygdala-frontal and frontal-striatal regions, as well as within and between canonical “intrinsic” brain networks - the default mode and salience networks, and that evidence of these aberrations may help inform findings of regional activation abnormalities observed in the anxiety disorders. Nonetheless, significant challenges remain, including the need to better understand mixed findings observed using different methods (e.g., resting state and task-based approaches); the need for more developmental work; the need to delineate disorder-specific and transdiagnostic fcMRI aberrations in the anxiety disorders; and the need to better understand the clinical significance of fcMRI abnormalities. In meeting these challenges, future work has the potential to elucidate aberrant neural networks as intermediate, brain-based phenotypes to predict disease onset and progression, refine diagnostic nosology, and ascertain treatment mechanisms and predictors of treatment response across anxiety, trauma-related and obsessive compulsive disorders. PMID:27141532

Diode probes for spatiotemporal optical control of multiple neurons in freely moving animals

PubMed Central

Koos, Tibor; Buzsáki, György

2012-01-01

Neuronal control with high temporal precision is possible with optogenetics, yet currently available methods do not enable to control independently multiple locations in the brains of freely moving animals. Here, we describe a diode-probe system that allows real-time and location-specific control of neuronal activity at multiple sites. Manipulation of neuronal activity in arbitrary spatiotemporal patterns is achieved by means of an optoelectronic array, manufactured by attaching multiple diode-fiber assemblies to high-density silicon probes or wire tetrodes and implanted into the brains of animals that are expressing light-responsive opsins. Each diode can be controlled separately, allowing localized light stimulation of neuronal activators and silencers in any temporal configuration and concurrent recording of the stimulated neurons. Because the only connections to the animals are via a highly flexible wire cable, unimpeded behavior is allowed for circuit monitoring and multisite perturbations in the intact brain. The capacity of the system to generate unique neural activity patterns facilitates multisite manipulation of neural circuits in a closed-loop manner and opens the door to addressing novel questions. PMID:22496529

Spatiotemporal regulation of autophagy during Caenorhabditis elegans aging

PubMed Central

Chang, Jessica T; Kumsta, Caroline; Hellman, Andrew B; Adams, Linnea M; Hansen, Malene

2017-01-01

Autophagy has been linked to longevity in many species, but the underlying mechanisms are unclear. Using a GFP-tagged and a new tandem-tagged Atg8/LGG-1 reporter, we quantified autophagic vesicles and performed autophagic flux assays in multiple tissues of wild-type Caenorhabditis elegans and long-lived daf-2/insulin/IGF-1 and glp-1/Notch mutants throughout adulthood. Our data are consistent with an age-related decline in autophagic activity in the intestine, body-wall muscle, pharynx, and neurons of wild-type animals. In contrast, daf-2 and glp-1 mutants displayed unique age- and tissue-specific changes in autophagic activity, indicating that the two longevity paradigms have distinct effects on autophagy during aging. Although autophagy appeared active in the intestine of both long-lived mutants, inhibition of intestinal autophagy significantly abrogated lifespan extension only in glp-1 mutants. Collectively, our data suggest that autophagic activity normally decreases with age in C. elegans, whereas daf-2 and glp-1 long-lived mutants regulate autophagy in distinct spatiotemporal-specific manners to extend lifespan. DOI: http://dx.doi.org/10.7554/eLife.18459.001 PMID:28675140

The efficiency of aspheric intraocular lens according to biometric measurements.

PubMed

Whang, Woong-Joo; Piao, Junjie; Yoo, Young-Sik; Joo, Choun-Ki; Yoon, Geunyoung

2017-01-01

To analyze internal spherical aberration in pseudophakic eyes that underwent aspheric intraocular lens (IOL) implantation, and to investigate the relationships between biometric data and the effectiveness of aspheric IOL implantation. This retrospective study included 40 eyes of 40 patients who underwent implantation of an IOL having a negative spherical aberration of -0.20 μm (CT ASPHINA 509M; Carl Zeiss Meditec Inc., Germany). The IOLMaster (version 5.0; Carl Zeiss AG, Germany) was used for preoperative biometric measurements (axial length, anterior chamber depth, central corneal power) and the measurement of postoperative anterior chamber depth. The spherical aberrations were measured preoperatively and 3 months postoperatively using the iTrace (Tracey Technologies, Houston, TX, USA) at a pupil diameter of 5.0 mm. We investigated the relationships between preoperative biometric data and postoperative internal spherical aberration, and compared biometric measurements between 2 subgroups stratified according to internal spherical aberration (spherical aberration ≤ -0.06 μm vs. spherical aberration > -0.06 μm). The mean postoperative internal spherical aberration was -0.087 ± 0.063 μm. Preoperative axial length and residual total spherical aberration showed statistically significant correlations with internal spherical aberration (p = 0.041, 0.002). Preoperative axial length, postoperative anterior chamber depth, IOL power, and residual spherical aberration showed significant differences between the 2 subgroups stratified according to internal spherical aberration (p = 0.020, 0.029, 0.048, 0.041 respectively). The corrective effect of an aspheric IOL is influenced by preoperative axial length and postoperative anterior chamber depth. Not only the amount of negative spherical aberration on the IOL surface but also the preoperative axial length should be considered to optimize spherical aberration after aspheric IOL implantation.

Aberrant Functional Activation in School Age Children At-Risk for Mathematical Disability: A Functional Imaging Study of Simple Arithmetic Skill

ERIC Educational Resources Information Center

Davis, Nicole; Cannistraci, Christopher J.; Rogers, Baxter P.; Gatenby, J. Christopher; Fuchs, Lynn S.; Anderson, Adam W.; Gore, John C.

2009-01-01

We used functional magnetic resonance imaging (fMRI) to explore the patterns of brain activation associated with different levels of performance in exact and approximate calculation tasks in well-defined cohorts of children with mathematical calculation difficulties (MD) and typically developing controls. Both groups of children activated the same…

Functional characterization of somatic mutations in cancer using network-based inference of protein activity | Office of Cancer Genomics

Cancer.gov

Identifying the multiple dysregulated oncoproteins that contribute to tumorigenesis in a given patient is crucial for developing personalized treatment plans. However, accurate inference of aberrant protein activity in biological samples is still challenging as genetic alterations are only partially predictive and direct measurements of protein activity are generally not feasible.

Towards cross-lingual alerting for bursty epidemic events.

PubMed

Collier, Nigel

2011-10-06

Online news reports are increasingly becoming a source for event-based early warning systems that detect natural disasters. Harnessing the massive volume of information available from multilingual newswire presents as many challanges as opportunities due to the patterns of reporting complex spatio-temporal events. In this article we study the problem of utilising correlated event reports across languages. We track the evolution of 16 disease outbreaks using 5 temporal aberration detection algorithms on text-mined events classified according to disease and outbreak country. Using ProMED reports as a silver standard, comparative analysis of news data for 13 languages over a 129 day trial period showed improved sensitivity, F1 and timeliness across most models using cross-lingual events. We report a detailed case study analysis for Cholera in Angola 2010 which highlights the challenges faced in correlating news events with the silver standard. The results show that automated health surveillance using multilingual text mining has the potential to turn low value news into high value alerts if informed choices are used to govern the selection of models and data sources. An implementation of the C2 alerting algorithm using multilingual news is available at the BioCaster portal http://born.nii.ac.jp/?page=globalroundup.

L1CAM in the Early Enteric and Urogenital System

PubMed Central

Pechriggl, Elisabeth Judith; Concin, Nicole; Blumer, Michael J.; Bitsche, Mario; Zwierzina, Marit; Dudas, Jozsef; Koziel, Katarzyna; Altevogt, Peter; Zeimet, Alain-Gustave; Fritsch, Helga

2016-01-01

L1 cell adhesion molecule (L1CAM) is a transmembrane molecule belonging to the L1 protein family. It has shown to be a key player in axonal guidance in the course of neuronal development. Furthermore, L1CAM is also crucial for the establishment of the enteric and urogenital organs and is aberrantly expressed in cancer originating in these organs. Carcinogenesis and embryogenesis follow a lot of similar molecular pathways, but unfortunately, comprehensive data on L1CAM expression and localization in human developing organs are lacking so far. In the present study we, therefore, examined the spatiotemporal distribution of L1CAM in the early human fetal period (weeks 8–12 of gestation) by means of immunohistochemistry and in situ hybridization (ISH). In the epithelia of the gastrointestinal organs, L1CAM localization cannot be observed in the examined stages most likely due to their advanced polarization and differentiation. Despite these results, our ISH data indicate weak L1CAM expression, but only in few epithelial cells. The genital tracts, however, are distinctly L1CAM positive throughout the entire fetal period. We, therefore, conclude that in embryogenesis L1CAM is crucial for further differentiation of epithelia. PMID:28026654

Fusion of the SUMO/Sentrin-specific protease 1 gene SENP1 and the embryonic polarity-related mesoderm development gene MESDC2 in a patient with an infantile teratoma and a constitutional t(12;15)(q13;q25).

PubMed

Veltman, Imke M; Vreede, Lilian A; Cheng, Jinke; Looijenga, Leendert H J; Janssen, Bert; Schoenmakers, Eric F P M; Yeh, Edward T H; van Kessel, Ad Geurts

2005-07-15

Recently, we identified a patient with an infantile sacrococcygeal teratoma and a constitutional t(12;15)(q13;q25). Here, we show that, as a result of this chromosomal translocation, the SUMO/Sentrin-specific protease 1 gene (SENP1) on chromosome 12 and the embryonic polarity-related mesoderm development gene (MESDC2) on chromosome 15 are disrupted and fused. Both reciprocal SENP1-MESDC2 (SEME) and MESDC2-SENP1 (MESE) fusion genes are transcribed in tumor-derived cells and their open reading frames encode aberrant proteins. As a consequence of this, and in contrast to wild-type (WT) MESDC2, the translocation-associated SEME protein is no longer targeted to the endoplasmatic reticulum, leading to a presumed loss-of-function as a chaperone for the WNT co-receptors LRP5 and/or LRP6. Ultimately, this might lead to abnormal development and/or routing of germ cell tumor precursor cells. SUMO, a post-translational modifier, plays an important role in several cellular key processes and is cleaved from its substrates by WT SENP1. Using a PML desumoylation assay, we found that translocation-associated MESE proteins exhibit desumoylation capacities similar to those observed for WT SENP1. We speculate that spatio-temporal disturbances in desumoylating activities during critical stages of embryonic development might have predisposed the patient. Together, the constitutional t(12;15)(q13;q25) translocation revealed two novel candidate genes for neonatal/infantile GCT development: MESDC2 and SENP1.

Imaging characteristics of Zernike and annular polynomial aberrations.

PubMed

Mahajan, Virendra N; Díaz, José Antonio

2013-04-01

The general equations for the point-spread function (PSF) and optical transfer function (OTF) are given for any pupil shape, and they are applied to optical imaging systems with circular and annular pupils. The symmetry properties of the PSF, the real and imaginary parts of the OTF, and the modulation transfer function (MTF) of a system with a circular pupil aberrated by a Zernike circle polynomial aberration are derived. The interferograms and PSFs are illustrated for some typical polynomial aberrations with a sigma value of one wave, and 3D PSFs and MTFs are shown for 0.1 wave. The Strehl ratio is also calculated for polynomial aberrations with a sigma value of 0.1 wave, and shown to be well estimated from the sigma value. The numerical results are compared with the corresponding results in the literature. Because of the same angular dependence of the corresponding annular and circle polynomial aberrations, the symmetry properties of systems with annular pupils aberrated by an annular polynomial aberration are the same as those for a circular pupil aberrated by a corresponding circle polynomial aberration. They are also illustrated with numerical examples.

Subjective depth of field in presence of 4th-order and 6th-order Zernike spherical aberration using adaptive optics technology.

PubMed

Benard, Yohann; Lopez-Gil, Norberto; Legras, Richard

2010-12-01

To study the impact on the subjective depth of field of 4th-order spherical aberration and its combination with 6th-order spherical aberration and analyze the accuracy of image-quality metrics in predicting the impact. Laboratoire Aimé Cotton, Centre National de la Recherche Scientifique, Université Paris-Sud, Orsay, France. Case series. Subjective depth of field was defined as the range of defocus at which the target (3 high-contrast letters at 20/50) was perceived acceptable. Depth of field was measured using 0.18 diopter (D) steps in young subjects with the addition of the following spherical aberration values: ±0.3 μm and ±0.6 μm 4th-order spherical aberration with 3.0 mm and 6.0 mm pupils and ±0.3 μm 4th-order spherical aberration with ±0.1 μm 6th-order spherical aberration for 6.0 mm pupils. The addition of ±0.3 and ±0.6 μm 4th-order spherical aberration increased depth of field by 30% and 45%, respectively. The combination of 4th-order spherical aberration and 6th-order spherical aberration of opposite signs increased depth of field more than 4th-order spherical aberration alone (ie, 63%), while the combination of 4th-order spherical aberration and 6th-order spherical aberration of the same signs did not (ie, 24%). Whereas the midpoint of the depth of field could be predicted by image-quality metrics, none was found a good predictor of objectionable depth of field. Subjective depth of field increased when 4th-order spherical aberration and 6th-order spherical aberration of opposite signs were added but could not be predicted with image-quality metrics. Copyright © 2010 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

Correlations between corneal and total wavefront aberrations

NASA Astrophysics Data System (ADS)

Mrochen, Michael; Jankov, Mirko; Bueeler, Michael; Seiler, Theo

2002-06-01

Purpose: Corneal topography data expressed as corneal aberrations are frequently used to report corneal laser surgery results. However, the optical image quality at the retina depends on all optical elements of the eye such as the human lens. Thus, the aim of this study was to investigate the correlations between the corneal and total wavefront aberrations and to discuss the importance of corneal aberrations for representing corneal laser surgery results. Methods: Thirty three eyes of 22 myopic subjects were measured with a corneal topography system and a Tschernig-type wavefront analyzer after the pupils were dilated to at least 6 mm in diameter. All measurements were centered with respect to the line of sight. Corneal and total wavefront aberrations were calculated up to the 6th Zernike order in the same reference plane. Results: Statistically significant correlations (p < 0.05) between the corneal and total wavefront aberrations were found for the astigmatism (C3,C5) and all 3rd Zernike order coefficients such as coma (C7,C8). No statistically significant correlations were found for all 4th to 6th order Zernike coefficients except for the 5th order horizontal coma C18 (p equals 0.003). On average, all Zernike coefficients for the corneal aberrations were found to be larger compared to Zernike coefficients for the total wavefront aberrations. Conclusions: Corneal aberrations are only of limited use for representing the optical quality of the human eye after corneal laser surgery. This is due to the lack of correlation between corneal and total wavefront aberrations in most of the higher order aberrations. Besides this, the data present in this study yield towards an aberration balancing between corneal aberrations and the optical elements within the eye that reduces the aberration from the cornea by a certain degree. Consequently, ideal customized ablations have to take both, corneal and total wavefront aberrations, into consideration.

Examination of the health status of populations from depleted-uranium-contaminated regions.

PubMed

Milacić, Snezana; Petrović, Dragana; Jovicić, Dubravka; Kovacević, Radomir; Simić, Jadranko

2004-05-01

During the NATO air strikes on the Federal Republic of Yugoslavia (Serbia and Montenegro) in 1999, depleted-uranium ammunition was used on 112 locations, mainly Kosovo, in the south of Serbia, and one location in Montenegro. Blood samples of residents from depleted-uranium-contaminated areas were gathered and blood cell and chromosomal aberrations were analyzed. During the last 3 years blood samples from 21 residents of Kosovo (Strpce), from 29 residents from the south of Serbia (the Vranje and Bujanovac regions), and from 19 technical television workers from the site of Pljackovica, in the vicinity of Vranje, were collected. Blood samples from 33 residents of central Serbia and 46 occupational workers exposed to X-rays were used as controls. All subjects studied were without any clinical symptoms of disease. The examinations included general clinical assessment; urine samples for alpha-and gamma-spectrometry analysis; complete blood counts; ratio-percentages of blood cells in stained (Giemsa) capillary smears, individual leukocyte line elements; morphological changes observed under a microscope; the presence of immature forms or blasts; and leukocyte enzyme activity [alkaline phosphatase leukocyte (APL)]. Chromosomal aberrations were evaluated in 200 peripheral blood lymphocytes in mitosis. An increased incidence of rogue cells and chromosomal aberrations was found in the blood of the residents of Vranje and Bujanovac, but this was below the incidence of chromosomal aberrations in individuals occupationally exposed to ionizing irradiation. Blast cells were not found. Blood counts were decreased in only a few samples, while morphological changes of both nuclei and cytoplasm were marked in individuals in south and central Serbia. Enzymatic activity (as measured by the APL score) was decreased in samples with chromosomal aberrations and cyto-morphological changes in subjects from the south of Serbia. The contamination level measured by this examination was low. Because of the presence of depleted uranium (uranium-238) in the soil and in plants, the prevention of consequences necessitates the identification of the initial biological effects on sensitive tissues. Early identification of serious blood cell changes is important for appropriate medical treatment.

Effect of aspirin on chromosome aberration and DNA damage induced by X-rays in mice

NASA Astrophysics Data System (ADS)

Niikawa, M.; Chuuriki, K.; Shibuya, K.; Seo, M.; Nagase, H.

In order to reveal the anticlastogenic potency of aspirin, we evaluated the suppressive ability of aspirin on chromosome aberrations induced by X-ray. Aspirin at doses of 0.5, 5 and 50 mg/kg was administrated intraperitoneally or orally at 0.5 h after or before the X-ray irradiation. The anticlastogenic activity of aspirin on chromosome aberrations induced by X-ray was determined in the mouse micronucleus test and alkaline single cell gel electrophoresis (SCG) assay in vivo. The frequency by polychromatic erythrocytes with micronuclei (MNPCEs) was decreased by about 19-61% at 0.5 h after and about 23-62% at 0.5 h before the X-ray irradiation. DNA damage by X-ray was significantly decreased by oral administration of aspirin at 0.5 h after or before the X-ray irradiation for the SCG assay. We consider aspirin can be used as preventive agents against exposure of X-ray.

Seeing Earth's Orbit in the Stars: Parallax and Aberration

NASA Astrophysics Data System (ADS)

Timberlake, Todd K.

2013-11-01

During the 17th century the idea of an orbiting and rotating Earth became increasingly popular, but opponents of this view continued to point out that the theory had observable consequences that had never, in fact, been observed.1 Why, for instance, had astronomers failed to detect the annual parallax of the stars that must occur if Earth orbits the Sun? To address this problem, astronomers of the 17th and 18th centuries sought to measure the annual parallax of stars using telescopes. None of them succeeded. Annual stellar parallax was not successfully measured until 1838, when Friedrich Bessel detected the parallax of the star 61 Cygni.2 But the early failures to detect annual stellar parallax led to the discovery of a new (and entirely unexpected) phenomenon: the aberration of starlight. This paper recounts the story of the discovery of stellar aberration. It is accompanied by a set of activities and computer simulations that allow students to explore this fascinating historical episode and learn important lessons about the nature of science.3

HOTS: A Hierarchy of Event-Based Time-Surfaces for Pattern Recognition.

PubMed

Lagorce, Xavier; Orchard, Garrick; Galluppi, Francesco; Shi, Bertram E; Benosman, Ryad B

2017-07-01

This paper describes novel event-based spatio-temporal features called time-surfaces and how they can be used to create a hierarchical event-based pattern recognition architecture. Unlike existing hierarchical architectures for pattern recognition, the presented model relies on a time oriented approach to extract spatio-temporal features from the asynchronously acquired dynamics of a visual scene. These dynamics are acquired using biologically inspired frameless asynchronous event-driven vision sensors. Similarly to cortical structures, subsequent layers in our hierarchy extract increasingly abstract features using increasingly large spatio-temporal windows. The central concept is to use the rich temporal information provided by events to create contexts in the form of time-surfaces which represent the recent temporal activity within a local spatial neighborhood. We demonstrate that this concept can robustly be used at all stages of an event-based hierarchical model. First layer feature units operate on groups of pixels, while subsequent layer feature units operate on the output of lower level feature units. We report results on a previously published 36 class character recognition task and a four class canonical dynamic card pip task, achieving near 100 percent accuracy on each. We introduce a new seven class moving face recognition task, achieving 79 percent accuracy.This paper describes novel event-based spatio-temporal features called time-surfaces and how they can be used to create a hierarchical event-based pattern recognition architecture. Unlike existing hierarchical architectures for pattern recognition, the presented model relies on a time oriented approach to extract spatio-temporal features from the asynchronously acquired dynamics of a visual scene. These dynamics are acquired using biologically inspired frameless asynchronous event-driven vision sensors. Similarly to cortical structures, subsequent layers in our hierarchy extract increasingly abstract features using increasingly large spatio-temporal windows. The central concept is to use the rich temporal information provided by events to create contexts in the form of time-surfaces which represent the recent temporal activity within a local spatial neighborhood. We demonstrate that this concept can robustly be used at all stages of an event-based hierarchical model. First layer feature units operate on groups of pixels, while subsequent layer feature units operate on the output of lower level feature units. We report results on a previously published 36 class character recognition task and a four class canonical dynamic card pip task, achieving near 100 percent accuracy on each. We introduce a new seven class moving face recognition task, achieving 79 percent accuracy.

Effect of aberrations in human eye on contrast sensitivity function

NASA Astrophysics Data System (ADS)

Quan, Wei; Wang, Feng-lin; Wang, Zhao-qi

2011-06-01

The quantitative analysis of the effect of aberrations in human eye on vision has important clinical value in the correction of aberrations. The wave-front aberrations of human eyes were measured with the Hartmann-Shack wave-front sensor and modulation transfer function (MTF) was computed from the wave-front aberrations. Contrast sensitivity function (CSF) was obtained from MTF and the retinal aerial image modulation (AIM). It is shown that the 2nd, 3rd, 4th, 5th, 6th Zernike aberrations deteriorate contrast sensitivity function. When the 2nd, 3rd, 4th, 5th, 6th Zernike aberrations are corrected high contrast sensitivity function can be obtained.

Optimization of auxiliary optics in active-optics telescopes

NASA Astrophysics Data System (ADS)

Ragazzoni, Roberto

1993-04-01

The a-priori knowledge of the availability of active optics in a telescope can be advantageous in the design, optimization, and specification of tolerances for auxiliary devices of such a telescope. A modification of the merit function to be used into the optimization process is given, together with some considerations about the design procedure. The different effects of aberrations typically depending upon the position of the field of view (like coma or astigmatism), with those typically constant over the whole field of view (like spherical aberration) are explicitly taken into account in the mathematical treatment. A possible range of applications (prime focus corrector, off-axis field corrector, field flattener, reducing camera, and so on) is discussed. A case study for a field flattener is shown. The general result that can be derived from this paper is that tolerances are generally strongly relaxed, while a significant improvement of the nominal performances can be obtained only in particular cases or assuming a high dynamic range of the active optics correction.

Tau and β-Amyloid Are Associated with Medial Temporal Lobe Structure, Function, and Memory Encoding in Normal Aging

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

Marks, Shawn M.; Lockhart, Samuel N.; Baker, Suzanne L.

Normal aging is associated with a decline in episodic memory and also with aggregation of the β-amyloid (Aβ) and tau proteins and atrophy of medial temporal lobe (MTL) structures crucial to memory formation. Although some evidence suggests that Aβ is associated with aberrant neural activity, the relationships among these two aggregated proteins, neural function, and brain structure are poorly understood. Using in vivo human Aβ and tau imaging, we demonstrate that increased Aβ and tau are both associated with aberrant fMRI activity in the MTL during memory encoding in cognitively normal older adults. This pathological neural activity was in turnmore » associated with worse memory performance and atrophy within the MTL. A mediation analysis revealed that the relationship with regional atrophy was explained by MTL tau. These findings broaden the concept of cognitive aging to include evidence of Alzheimer’s disease-related protein aggregation as an underlying mechanism of age-related memory impairment.« less

Spatiotemporal stochastic models for earth science and engineering applications

NASA Astrophysics Data System (ADS)

Luo, Xiaochun

1998-12-01

Spatiotemporal processes occur in many areas of earth sciences and engineering. However, most of the available theoretical tools and techniques of space-time daft processing have been designed to operate exclusively in time or in space, and the importance of spatiotemporal variability was not fully appreciated until recently. To address this problem, a systematic framework of spatiotemporal random field (S/TRF) models for geoscience/engineering applications is presented and developed in this thesis. The space-tune continuity characterization is one of the most important aspects in S/TRF modelling, where the space-time continuity is displayed with experimental spatiotemporal variograms, summarized in terms of space-time continuity hypotheses, and modelled using spatiotemporal variogram functions. Permissible spatiotemporal covariance/variogram models are addressed through permissibility criteria appropriate to spatiotemporal processes. The estimation of spatiotemporal processes is developed in terms of spatiotemporal kriging techniques. Particular emphasis is given to the singularity analysis of spatiotemporal kriging systems. The impacts of covariance, functions, trend forms, and data configurations on the singularity of spatiotemporal kriging systems are discussed. In addition, the tensorial invariance of universal spatiotemporal kriging systems is investigated in terms of the space-time trend. The conditional simulation of spatiotemporal processes is proposed with the development of the sequential group Gaussian simulation techniques (SGGS), which is actually a series of sequential simulation algorithms associated with different group sizes. The simulation error is analyzed with different covariance models and simulation grids. The simulated annealing technique honoring experimental variograms, is also proposed, providing a way of conditional simulation without the covariance model fitting which is prerequisite for most simulation algorithms. The proposed techniques were first applied for modelling of the pressure system in a carbonate reservoir, and then applied for modelling of springwater contents in the Dyle watershed. The results of these case studies as well as the theory suggest that these techniques are realistic and feasible.

Spiral wave classification using normalized compression distance: Towards atrial tissue spatiotemporal electrophysiological behavior characterization.

PubMed

Alagoz, Celal; Guez, Allon; Cohen, Andrew; Bullinga, John R

2015-08-01

Analysis of electrical activation patterns such as re-entries during atrial fibrillation (Afib) is crucial in understanding arrhythmic mechanisms and assessment of diagnostic measures. Spiral waves are a phenomena that provide intuitive basis for re-entries occurring in cardiac tissue. Distinct spiral wave behaviors such as stable spiral waves, meandering spiral waves, and spiral wave break-up may have distinct electrogram manifestations on a mapping catheter. Hence, it is desirable to have an automated classification of spiral wave behavior based on catheter recordings for a qualitative characterization of spatiotemporal electrophysiological activity on atrial tissue. In this study, we propose a method for classification of spatiotemporal characteristics of simulated atrial activation patterns in terms of distinct spiral wave behaviors during Afib using two different techniques: normalized compressed distance (NCD) and normalized FFT (NFFTD). We use a phenomenological model for cardiac electrical propagation to produce various simulated spiral wave behaviors on a 2D grid and labeled them as stable, meandering, or breakup. By mimicking commonly used catheter types, a star shaped and a circular shaped both of which do the local readings from atrial wall, monopolar and bipolar intracardiac electrograms are simulated. Virtual catheters are positioned at different locations on the grid. The classification performance for different catheter locations, types and for monopolar or bipolar readings were also compared. We observed that the performance for each case differed slightly. However, we found that NCD performance is superior to NFFTD. Through the simulation study, we showed the theoretical validation of the proposed method. Our findings suggest that a qualitative wavefront activation pattern can be assessed during Afib without the need for highly invasive mapping techniques such as multisite simultaneous electrogram recordings.

Working memory load-dependent spatio-temporal activity of single-trial P3 response detected with an adaptive wavelet denoiser.

PubMed

Zhang, Qiushi; Yang, Xueqian; Yao, Li; Zhao, Xiaojie

2017-03-27

Working memory (WM) refers to the holding and manipulation of information during cognitive tasks. Its underlying neural mechanisms have been explored through both functional magnetic resonance imaging (fMRI) and electroencephalography (EEG). Trial-by-trial coupling of simultaneously collected EEG and fMRI signals has become an important and promising approach to study the spatio-temporal dynamics of such cognitive processes. Previous studies have demonstrated a modulation effect of the WM load on both the BOLD response in certain brain areas and the amplitude of P3. However, much remains to be explored regarding the WM load-dependent relationship between the amplitude of ERP components and cortical activities, and the low signal-to-noise ratio (SNR) of the EEG signal still poses a challenge to performing single-trial analyses. In this paper, we investigated the spatio-temporal activities of P3 during an n-back verbal WM task by introducing an adaptive wavelet denoiser into the extraction of single-trial P3 features and using general linear model (GLM) to integrate simultaneously collected EEG and fMRI data. Our results replicated the modulation effect of the WM load on the P3 amplitude. Additionally, the activation of single-trial P3 amplitudes was detected in multiple brain regions, including the insula, the cuneus, the lingual gyrus (LG), and the middle occipital gyrus (MOG). Moreover, we found significant correlations between P3 features and behavioral performance. These findings suggest that the single-trial integration of simultaneous EEG and fMRI signals may provide new insights into classical cognitive functions. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Asymmetric spatiotemporal chaos induced by a polypoid mass in the excised larynx

PubMed Central

Zhang, Yu; Jiang, Jack J.

2008-01-01

In this paper, asymmetric spatiotemporal chaos induced by a polypoid mass simulating the laryngeal pathology of a vocal polyp is experimentally observed using high-speed imaging in an excised larynx. Spatiotemporal analysis reveals that the normal vocal folds show spatiotemporal correlation and symmetry. Normal vocal fold vibrations are dominated mainly by the first vibratory eigenmode. However, pathological vocal folds with a polypoid mass show broken symmetry and spatiotemporal irregularity. The spatial correlation is decreased. The pathological vocal folds spread vibratory energy across a large number of eigenmodes and induce asymmetric spatiotemporal chaos. High-order eigenmodes show complicated dynamics. Spatiotemporal analysis provides a valuable biomedical application for investigating the spatiotemporal chaotic dynamics of pathological vocal fold systems with a polypoid mass and may represent a valuable clinical tool for the detection of laryngeal mass lesion using high-speed imaging. PMID:19123612

CXCL12 Mediates Aberrant Costimulation of B Lymphocytes in Warts, Hypogammaglobulinemia, Infections, Myelokathexis Immunodeficiency

PubMed Central

Roselli, Giuliana; Martini, Elisa; Lougaris, Vassilios; Badolato, Raffaele; Viola, Antonella; Kallikourdis, Marinos

2017-01-01

The Warts, Hypogammaglobulinemia, Infections, Myelokathexis (WHIM) syndrome is an immunodeficiency caused by mutations in chemokine receptor CXCR4. WHIM patient adaptive immunity defects remain largely unexplained. We have previously shown that WHIM-mutant T cells form unstable immunological synapses, affecting T cell activation. Here, we show that, in WHIM patients and WHIM CXCR4 knock-in mice, B cells are more apoptosis prone. Intriguingly, WHIM-mutant B cells were also characterized by spontaneous activation. Searching for a mechanistic explanation for these observations, we uncovered a novel costimulatory effect of CXCL12, the CXCR4 ligand, on WHIM-mutant but not wild-type B cells. The WHIM CXCR4-mediated costimulation led to increased B-cell activation, possibly involving mTOR, albeit without concurrently promoting survival. A reduction in antigenic load during immunization in the mouse was able to circumvent the adaptive immunity defects. These results suggest that WHIM-mutant CXCR4 may lead to spontaneous aberrant B-cell activation, via CXCL12-mediated costimulation, impairing B-cell survival and thus possibly contributing to the WHIM syndrome defects in adaptive immunity. PMID:28928741

Long-Acting Beta Agonists Enhance Allergic Airway Disease.

PubMed

Knight, John M; Mak, Garbo; Shaw, Joanne; Porter, Paul; McDermott, Catherine; Roberts, Luz; You, Ran; Yuan, Xiaoyi; Millien, Valentine O; Qian, Yuping; Song, Li-Zhen; Frazier, Vincent; Kim, Choel; Kim, Jeong Joo; Bond, Richard A; Milner, Joshua D; Zhang, Yuan; Mandal, Pijus K; Luong, Amber; Kheradmand, Farrah; McMurray, John S; Corry, David B

2015-01-01

Asthma is one of the most common of medical illnesses and is treated in part by drugs that activate the beta-2-adrenoceptor (β2-AR) to dilate obstructed airways. Such drugs include long acting beta agonists (LABAs) that are paradoxically linked to excess asthma-related mortality. Here we show that LABAs such as salmeterol and structurally related β2-AR drugs such as formoterol and carvedilol, but not short-acting agonists (SABAs) such as albuterol, promote exaggerated asthma-like allergic airway disease and enhanced airway constriction in mice. We demonstrate that salmeterol aberrantly promotes activation of the allergic disease-related transcription factor signal transducer and activator of transcription 6 (STAT6) in multiple mouse and human cells. A novel inhibitor of STAT6, PM-242H, inhibited initiation of allergic disease induced by airway fungal challenge, reversed established allergic airway disease in mice, and blocked salmeterol-dependent enhanced allergic airway disease. Thus, structurally related β2-AR ligands aberrantly activate STAT6 and promote allergic airway disease. This untoward pharmacological property likely explains adverse outcomes observed with LABAs, which may be overcome by agents that antagonize STAT6.

The Charles F. Prentice Award Lecture 2005: optics of the human eye: progress and problems.

PubMed

Charman, W Neil

2006-06-01

The history of measurements of ocular aberration is briefly reviewed and recent work using much-improved aberrometers and large samples of eyes is summarized. When on-axis, higher-order, monochromatic aberrations are averaged, undercorrected, positive, fourth-order spherical aberration dominates; other Zernike wavefront aberration coefficients have average values near zero. Individually, however, many eyes show substantial amounts of third-order and other fourth-order aberrations; the value of these varies idiosyncratically about zero. Most normal eyes show only small amounts of axial monochromatic aberration for photopic pupils up to around 3 mm; the limits to retinal image quality are then usually set by diffraction, uncorrected or imperfectly corrected spherocylindrical refractive error, accommodation error, and chromatic aberration. Longitudinal chromatic aberration varies very little across the population. With larger mesopic and scotopic pupils, monochromatic aberration plays a more important optical role, but overall visual performance is increasingly dominated by neural factors. Some remaining problems in measuring and modeling the eye's optical performance are discussed.

a Spatiotemporal Aggregation Query Method Using Multi-Thread Parallel Technique Based on Regional Division

NASA Astrophysics Data System (ADS)

Liao, S.; Chen, L.; Li, J.; Xiong, W.; Wu, Q.

2015-07-01

Existing spatiotemporal database supports spatiotemporal aggregation query over massive moving objects datasets. Due to the large amounts of data and single-thread processing method, the query speed cannot meet the application requirements. On the other hand, the query efficiency is more sensitive to spatial variation then temporal variation. In this paper, we proposed a spatiotemporal aggregation query method using multi-thread parallel technique based on regional divison and implemented it on the server. Concretely, we divided the spatiotemporal domain into several spatiotemporal cubes, computed spatiotemporal aggregation on all cubes using the technique of multi-thread parallel processing, and then integrated the query results. By testing and analyzing on the real datasets, this method has improved the query speed significantly.

Performance verification and environmental testing of a unimorph deformable mirror for space applications

NASA Astrophysics Data System (ADS)

Rausch, Peter; Verpoort, Sven; Wittrock, Ulrich

2017-11-01

Concepts for future large space telescopes require an active optics system to mitigate aberrations caused by thermal deformation and gravitational release. Such a system would allow on-site correction of wave-front errors and ease the requirements for thermal and gravitational stability of the optical train. In the course of the ESA project "Development of Adaptive Deformable Mirrors for Space Instruments" we have developed a unimorph deformable mirror designed to correct for low-order aberrations and dedicated to be used in space environment. We briefly report on design and manufacturing of the deformable mirror and present results from performance verifications and environmental testing.

Nodal aberration theory for wild-filed asymmetric optical systems

NASA Astrophysics Data System (ADS)

Chen, Yang; Cheng, Xuemin; Hao, Qun

2016-10-01

Nodal Aberration Theory (NAT) was used to calculate the zero field position in Full Field Display (FFD) for the given aberration term. Aiming at wide-filed non-rotational symmetric decentered optical systems, we have presented the nodal geography behavior of the family of third-order and fifth-order aberrations. Meanwhile, we have calculated the wavefront aberration expressions when one optical element in the system is tilted, which was not at the entrance pupil. By using a three-piece-cellphone lens example in optical design software CodeV, the nodal geography is testified under several situations; and the wavefront aberrations are calculated when the optical element is tilted. The properties of the nodal aberrations are analyzed by using Fringe Zernike coefficients, which are directly related with the wavefront aberration terms and usually obtained by real ray trace and wavefront surface fitting.

Orthonormal aberration polynomials for anamorphic optical imaging systems with rectangular pupils.

PubMed

Mahajan, Virendra N

2010-12-20

The classical aberrations of an anamorphic optical imaging system, representing the terms of a power-series expansion of its aberration function, are separable in the Cartesian coordinates of a point on its pupil. We discuss the balancing of a classical aberration of a certain order with one or more such aberrations of lower order to minimize its variance across a rectangular pupil of such a system. We show that the balanced aberrations are the products of two Legendre polynomials, one for each of the two Cartesian coordinates of the pupil point. The compound Legendre polynomials are orthogonal across a rectangular pupil and, like the classical aberrations, are inherently separable in the Cartesian coordinates of the pupil point. They are different from the balanced aberrations and the corresponding orthogonal polynomials for a system with rotational symmetry but a rectangular pupil.

3D resolved mapping of optical aberrations in thick tissues

PubMed Central

Zeng, Jun; Mahou, Pierre; Schanne-Klein, Marie-Claire; Beaurepaire, Emmanuel; Débarre, Delphine

2012-01-01

We demonstrate a simple method for mapping optical aberrations with 3D resolution within thick samples. The method relies on the local measurement of the variation in image quality with externally applied aberrations. We discuss the accuracy of the method as a function of the signal strength and of the aberration amplitude and we derive the achievable resolution for the resulting measurements. We then report on measured 3D aberration maps in human skin biopsies and mouse brain slices. From these data, we analyse the consequences of tissue structure and refractive index distribution on aberrations and imaging depth in normal and cleared tissue samples. The aberration maps allow the estimation of the typical aplanetism region size over which aberrations can be uniformly corrected. This method and data pave the way towards efficient correction strategies for tissue imaging applications. PMID:22876353

Influence of eye micromotions on spatially resolved refractometry

NASA Astrophysics Data System (ADS)

Chyzh, Igor H.; Sokurenko, Vyacheslav M.; Osipova, Irina Y.

2001-01-01

The influence eye micromotions on the accuracy of estimation of Zernike coefficients form eye transverse aberration measurements was investigated. By computer modeling, the following found eye aberrations have been examined: defocusing, primary astigmatism, spherical aberration of the 3rd and the 5th orders, as well as their combinations. It was determined that the standard deviation of estimated Zernike coefficients is proportional to the standard deviation of angular eye movements. Eye micromotions cause the estimation errors of Zernike coefficients of present aberrations and produce the appearance of Zernike coefficients of aberrations, absent in the eye. When solely defocusing is present, the biggest errors, cased by eye micromotions, are obtained for aberrations like coma and astigmatism. In comparison with other aberrations, spherical aberration of the 3rd and the 5th orders evokes the greatest increase of the standard deviation of other Zernike coefficients.

Seagrass mitigation site modeling and assessment.

DOT National Transportation Integrated Search

2013-05-01

Spatiotemporal analysis of Lake Surprise and SL-15 (15th spoil island in St. Lucie County) has allowed for a robust assessment of successful Florida Department of Transportation (FDOT) activities. Project results showed that bridge construction in La...

Total ocular, anterior corneal and lenticular higher order aberrations in hyperopic, myopic and emmetropic eyes.

PubMed

Philip, Krupa; Martinez, Aldo; Ho, Arthur; Conrad, Fabian; Ale, Jit; Mitchell, Paul; Sankaridurg, Padmaja

2012-01-01

Total ocular higher order aberrations and corneal topography of myopic, emmetropic and hyperopic eyes of 675 adolescents (16.9 ± 0.7 years) were measured after cycloplegia using COAS aberrometer and Medmont videokeratoscope. Corneal higher order aberrations were computed from the corneal topography maps and lenticular (internal) higher order aberrations derived by subtraction of corneal aberrations from total ocular aberrations. Aberrations were measured for a pupil diameter of 5mm. Multivariate analysis of variance followed by multiple regression analysis found significant difference in the fourth order aberrations (SA RMS, primary spherical aberration coefficient) between the refractive error groups. Hyperopic eyes (+0.083 ± 0.05 μm) had more positive total ocular primary spherical aberration compared to emmetropic (+0.036 ± 0.04 μm) and myopic eyes (low myopia=+0.038 ± 0.05 μm, moderate myopia=+0.026 ± 0.06 μm) (p<0.05). No difference was observed for the anterior corneal spherical aberration. Significantly less negative lenticular spherical aberration was observed for the hyperopic eyes (-0.038 ± 0.05 μm) than myopic (low myopia=-0.088 ± 0.04 μm, moderate myopia=-0.095 ± 0.05 μm) and emmetropic eyes (-0.081 ± 0.04 μm) (p<0.05). These findings suggest the existence of differences in the characteristics of the crystalline lens (asphericity, curvature and gradient refractive index) of hyperopic eyes versus other eyes. Crown Copyright © 2011. Published by Elsevier Ltd. All rights reserved.

Micrometric Control of the Optics of the Human Eye: Environment or Genes?

PubMed

Tabernero, Juan; Hervella, Lucía; Benito, Antonio; Colodro-Conde, Lucía; Ordoñana, Juan R; Ruiz-Sanchez, Marcos; Marín, José María; Artal, Pablo

2017-04-01

The human eye has typically more optical aberrations than conventional artificial optical systems. While the lower order modes (defocus and astigmatism) are well studied, our purpose is to explore the influence of genes versus the environment on the higher order aberrations of the optical components of the eye. We have performed a classical twin study in a sample from the Region of Murcia (Spain). Optical aberrations using a Hartmann-Shack sensor (AOnEye Voptica SL, Murcia, Spain) and corneal aberrations (using corneal topography data) were measured in 138 eyes corresponding to 69 twins; 36 monozygotic (MZ) and 33 dizygotic (DZ) pairs (age 55 years, SD 7 years). Intraclass correlation coefficients (ICCs) were used to estimate how strongly aberrations of twins resemble each other, and genetic models were fitted to quantify heritability in the selected phenotypes. Genes had a significant influence in the variance of most of the higher order aberration terms (heritability from 40% to 70%). This genetic influence was observed similarly in both cornea and complete eye aberrations. Additionally, the compensation factor of spherical aberration in the eye (i.e., how much corneal spherical aberration was compensated by internal spherical aberration) was found under genetic influence (heritability of 68%). There is a significant genetic contribution to the variance of aberrations of the eye, not only at macroscopic levels, as in myopia or astigmatism, but also at microscopic levels, where a few micrometers changes in surface topography can produce a large difference in the value of the optical aberrations.

Human seizures couple across spatial scales through travelling wave dynamics

NASA Astrophysics Data System (ADS)

Martinet, L.-E.; Fiddyment, G.; Madsen, J. R.; Eskandar, E. N.; Truccolo, W.; Eden, U. T.; Cash, S. S.; Kramer, M. A.

2017-04-01

Epilepsy--the propensity toward recurrent, unprovoked seizures--is a devastating disease affecting 65 million people worldwide. Understanding and treating this disease remains a challenge, as seizures manifest through mechanisms and features that span spatial and temporal scales. Here we address this challenge through the analysis and modelling of human brain voltage activity recorded simultaneously across microscopic and macroscopic spatial scales. We show that during seizure large-scale neural populations spanning centimetres of cortex coordinate with small neural groups spanning cortical columns, and provide evidence that rapidly propagating waves of activity underlie this increased inter-scale coupling. We develop a corresponding computational model to propose specific mechanisms--namely, the effects of an increased extracellular potassium concentration diffusing in space--that support the observed spatiotemporal dynamics. Understanding the multi-scale, spatiotemporal dynamics of human seizures--and connecting these dynamics to specific biological mechanisms--promises new insights to treat this devastating disease.

A neuronal model of a global workspace in effortful cognitive tasks.

PubMed

Dehaene, S; Kerszberg, M; Changeux, J P

1998-11-24

A minimal hypothesis is proposed concerning the brain processes underlying effortful tasks. It distinguishes two main computational spaces: a unique global workspace composed of distributed and heavily interconnected neurons with long-range axons, and a set of specialized and modular perceptual, motor, memory, evaluative, and attentional processors. Workspace neurons are mobilized in effortful tasks for which the specialized processors do not suffice. They selectively mobilize or suppress, through descending connections, the contribution of specific processor neurons. In the course of task performance, workspace neurons become spontaneously coactivated, forming discrete though variable spatio-temporal patterns subject to modulation by vigilance signals and to selection by reward signals. A computer simulation of the Stroop task shows workspace activation to increase during acquisition of a novel task, effortful execution, and after errors. We outline predictions for spatio-temporal activation patterns during brain imaging, particularly about the contribution of dorsolateral prefrontal cortex and anterior cingulate to the workspace.

[Spatiotemporal dynamic fuzzy evaluation of wetland environmental pollution risk in Dayang estuary of Liaoning Province, Northeast China based on remote sensing].

PubMed

Sun, Yong-Guang; Zhao, Dong-Zhi; Zhang, Feng-Shou; Wei, Bao-Quan; Chu, Jia-Lan; Su, Xiu

2012-11-01

Based on the aerial image data of Dayang estuary in 2008, and by virtue of Analytic Hierarchy Process (AHP) , remote sensing technology, and GIS spatial analysis, a spatiotemporal evaluation was made on the comprehensive level of wetland environmental pollution risk in Dayang estuary, with the impacts of typical human activities on the dynamic variation of this comprehensive level discussed. From 1958 to 2008, the comprehensive level of the environmental pollution risk in study area presented an increasing trend. Spatially, this comprehensive level declined from land to ocean, and showed a zonal distribution. Tourism development activities unlikely led to the increase of the comprehensive level, while human inhabitation, transportation, and aquaculture would exacerbate the risk of environmental pollution. This study could provide reference for the sea area use planning, ecological function planning, and pollutants control of estuary region.

Low-Energy Defibrillation Failure Correction is Possible Through Nonlinear Analysis of Spatiotemporal Arrhythmia Data

NASA Astrophysics Data System (ADS)

Simonotto, Jennifer; Furman, Michael; Beaver, Thomas; Spano, Mark; Kavanagh, Katherine; Iden, Jason; Hu, Gang; Ditto, William

2004-03-01

Explanted Porcine hearts were Langendorff-perfused, administered a voltage-sensitive fluorescent dye (Di-4-ANEPPS) and illuminated with a ND:Yag laser (532 nm); the change in fluorescence resulting from electrical activity on the heart surface was recorded with an 80 x 80 pixel CCD camera at 1000 frames per second. The heart was put into fibrillation with rapid ventricular pacing and shocks were administered close to the defibrillation threshold. Defibrillation failure data was analyzed using synchronization, space-time volume plots and recurrence quantification. Preliminary spatiotemporal synchronization results reveal a short window of time ( 1 second) after defibrillation failure in which the disordered electrical activity becomes ordered; this ordered period occurs 4-5 seconds after the defibrillation shock. Recurrence analysis of a single time series confirmed these results, thus opening the avenue for dynamic defibrillators that can detect an optimal window for cardioversion.

Increased biomagnetic activity in the ventral pathway in mild cognitive impairment.

PubMed

Maestú, F; Campo, P; Del Río, D; Moratti, S; Gil-Gregorio, P; Fernández, A; Capilla, A; Ortiz, T

2008-06-01

Mild cognitive impairment (MCI) patients represent an intermediary state between healthy aging and dementia. MCI activation profiles, recorded during a memory task, have been studied either through high spatial resolution or high temporal resolution techniques. However, little is known about the benefit of combining both dimensions. Here, we investigate, by means of magnetoencephalography (MEG), whether spatio-temporal profiles of neuromagnetic activity could differentiate between MCI and age-matched elderly participants. Taking the advantage of the high temporal resolution and good spatial resolution of MEG, neuromagnetic activity from 15 elderly MCI patients and 20 age-matched controls was recorded during the performance of a modified version of the Sternberg paradigm. Behavioral performance was similar in both groups. A between group analysis revealed that MCI patients showed bilateral higher activity in the ventral pathway, in both the target and the non-target stimuli. A within-group analysis of the target stimuli, indicates a lack of asymmetry through all late latency windows in both groups. MCI patients showed a compensatory mechanism represented by an increased bilateral activity of the ventral pathway in order to achieve a behavioral performance similar to the control group. This spatio-temporal pattern of activity could be another tool to differentiate between healthy aging and MCI patients.

Corneal Curvature, Astigmatism, and Aberrations in Marfan Syndrome with Lens Subluxation: Evaluation by Pentacam HR System.

PubMed

Chen, Jiahui; Jing, Qinghe; Tang, Yating; Qian, Dongjin; Lu, Yi; Jiang, Yongxiang

2018-03-06

Marfan syndrome (MFS) is associated with abnormalities of corneal biometric characteristics. We conducted a retrospective case-control study including 55 eyes of the MFS patients with lens subluxation and 53 normal eyes of the control subjects to evaluate the corneal curvature, astigmatism and aberrations using a rotating Scheimpflug camera (Pentacam HR). Compared with the control group, the anterior, posterior, and total corneal curvature were flatter in the MFS group. The anterior and total corneal astigmatism were higher in the MFS patients, whereas the posterior corneal astigmatism was not significantly different between the two groups. Regarding the total corneal aberrations, the root mean square (RMS) aberrations, RMS higher-order aberrations and RMS lower-order aberrations increased, whereas the spherical aberration decreased in the MFS patients. Corneal parameters had potential diagnostic values for MFS patients with lens subluxation and the more reasonable cutoffs were the values of corneal curvature <41.35 D, corneal astigmatism >0.85 D and spherical aberration <0.188 μm. Corneal biometric characteristics of MFS patients with lens subluxation include decreased corneal curvature, higher corneal astigmatism, larger corneal aberrations, and lower spherical aberration. Corneal curvature, corneal astigmatism, and spherical aberration are better diagnostic tools for suspicious MFS.

Comparison of Aberrations After Standard and Customized Refractive Surgery

NASA Astrophysics Data System (ADS)

Fang, L.; He, X.; Wang, Y.

2013-09-01

To detect possible differences in residual wavefront aberrations between standard and customized laser refractive surgery based onmathematical modeling, the residual optical aberrations after conventional and customized laser refractive surgery were compared accordingto the ablation profile with transition zone. The results indicated that ablation profile has a significant impact on the residual aberrations.The amount of residual aberrations for conventional correction is higher than that for customized correction. Additionally, the residualaberrations for high myopia eyes are markedly larger than those for moderate myopia eyes. For a 5 mm pupil, the main residual aberrationterm is coma and yet it is spherical aberration for a 7 mm pupil. When the pupil diameter is the same as optical zone or greater, themagnitudes of residual aberrations is obviously larger than that for a smaller pupil. In addition, the magnitudes of the residual fifth orsixth order aberrations are relatively large, especially secondary coma in a 6 mm pupil and secondary spherical aberration in a 7 mm pupil.Therefore, the customized ablation profile may be superior to the conventional correction even though the transition zone and treatmentdecentration are taken into account. However, the customized ablation profile will still induce significant amount of residual aberrations.

Monochromatic ocular wave aberrations in young monkeys

PubMed Central

Ramamirtham, Ramkumar; Kee, Chea-su; Hung, Li-Fang; Qiao-Grider, Ying; Roorda, Austin; Smith, Earl L.

2006-01-01

High-order monochromatic aberrations could potentially influence vision-dependent refractive development in a variety of ways. As a first step in understanding the effects of wave aberration on refractive development, we characterized the maturational changes that take place in the high-order aberrations of infant rhesus monkey eyes. Specifically, we compared the monochromatic wave aberrations of infant and adolescent animals and measured the longitudinal changes in the high-order aberrations of infant monkeys during the early period when emmetropization takes place. Our main findings were that (1) adolescent monkey eyes have excellent optical quality, exhibiting total RMS errors that were slightly better than those for adult human eyes that have the same numerical aperture and (2) shortly after birth, infant rhesus monkeys exhibited relatively larger magnitudes of high-order aberrations predominately spherical aberration, coma, and trefoil, which decreased rapidly to assume adolescent values by about 200 days of age. The results demonstrate that rhesus monkey eyes are a good model for studying the contribution of individual ocular components to the eye’s overall aberration structure, the mechanisms responsible for the improvements in optical quality that occur during early ocular development, and the effects of high-order aberrations on ocular growth and emmetropization. PMID:16750549

Aberration design of zoom lens systems using thick lens modules.

PubMed

Zhang, Jinkai; Chen, Xiaobo; Xi, Juntong; Wu, Zhuoqi

2014-12-20

A systematic approach for the aberration design of a zoom lens system using a thick lens module is presented. Each component is treated as a thick lens module at the beginning of the design. A thick lens module refers to a thick lens component with a real lens structure, like lens materials, lens curvatures, lens thicknesses, and lens interval distances. All nine third-order aberrations of a thick lens component are considered during the design. The relationship of component aberrations in different zoom positions can be approximated from the aberration shift. After minimizing the aberrations of the zoom lens system, the nine third-order aberrations of every lens component can be determined. Then the thick lens structure of every lens component can be determined after optimization according to their first-order properties and third-order aberration targets. After a third optimization for minimum practical third-order aberrations of a zoom lens system, the aberration design using the thick lens module is complete, which provides a practical zoom lens system with thick lens structures. A double-sided telecentric zoom lens system is designed using the thick lens module in this paper, which shows that this method is practical for zoom lens design.

DNA Repair Defects and Chromosomal Aberrations

NASA Technical Reports Server (NTRS)

Hada, Megumi; George, K. A.; Huff, J. L.; Pluth, J. M.; Cucinotta, F. A.

2009-01-01

Yields of chromosome aberrations were assessed in cells deficient in DNA doublestrand break (DSB) repair, after exposure to acute or to low-dose-rate (0.018 Gy/hr) gamma rays or acute high LET iron nuclei. We studied several cell lines including fibroblasts deficient in ATM (ataxia telangiectasia mutated; product of the gene that is mutated in ataxia telangiectasia patients) or NBS (nibrin; product of the gene mutated in the Nijmegen breakage syndrome), and gliomablastoma cells that are proficient or lacking in DNA-dependent protein kinase (DNA-PK) activity. Chromosomes were analyzed using the fluorescence in situ hybridization (FISH) chromosome painting method in cells at the first division post irradiation, and chromosome aberrations were identified as either simple exchanges (translocations and dicentrics) or complex exchanges (involving >2 breaks in 2 or more chromosomes). Gamma irradiation induced greater yields of both simple and complex exchanges in the DSB repair-defective cells than in the normal cells. The quadratic dose-response terms for both simple and complex chromosome exchanges were significantly higher for the ATM- and NBS-deficient lines than for normal fibroblasts. However, in the NBS cells the linear dose-response term was significantly higher only for simple exchanges. The large increases in the quadratic dose-response terms in these repair-defective cell lines points the importance of the functions of ATM and NBS in chromatin modifications to facilitate correct DSB repair and minimize the formation of aberrations. The differences found between ATM- and NBS-deficient cells at low doses suggest that important questions should with regard to applying observations of radiation sensitivity at high dose to low-dose exposures. For aberrations induced by iron nuclei, regression models preferred purely linear dose responses for simple exchanges and quadratic dose responses for complex exchanges. Relative biological effectiveness (RBE) factors of all of the DNA repair-defective cell lines were smaller than those of normal cells, with the DNA-PK-deficient cells having RBEs near unity. To further investigate the sensitivity differences that were observed in ATM and NBS deficient cells, chromosomal aberrations were analyzed in normal lung fibroblast cells treated with KU-55933 (a specific ATM kinase inhibitor) or Mirin (an Mre11- Rad50-Nbs1 complex inhibitor involved in activation of ATM). We also performed siRNA knockdown of these proteins. Preliminary data indicate that chromosome exchanges increase in cells treated with the specific ATM inhibitor. Possible cytogenetic signatures of acute and low dose-rate gamma irradiation in ATM or nibrin deficient and suppressed cells will be discussed.

Size-dependent diffusion promotes the emergence of spatiotemporal patterns

NASA Astrophysics Data System (ADS)

Zhang, Lai; Thygesen, Uffe Høgsbro; Banerjee, Malay

2014-07-01

Spatiotemporal patterns, indicating the spatiotemporal variability of individual abundance, are a pronounced scenario in ecological interactions. Most of the existing models for spatiotemporal patterns treat species as homogeneous groups of individuals with average characteristics by ignoring intraspecific physiological variations at the individual level. Here we explore the impacts of size variation within species resulting from individual ontogeny, on the emergence of spatiotemporal patterns in a fully size-structured population model. We found that size dependency of animal's diffusivity greatly promotes the formation of spatiotemporal patterns, by creating regular spatiotemporal patterns out of temporal chaos. We also found that size-dependent diffusion can substitute large-amplitude base harmonics with spatiotemporal patterns with lower amplitude oscillations but with enriched harmonics. Finally, we found that the single-generation cycle is more likely to drive spatiotemporal patterns compared to predator-prey cycles, meaning that the mechanism of Hopf bifurcation might be more common than hitherto appreciated since the former cycle is more widespread than the latter in case of interacting populations. Due to the ubiquity of individual ontogeny in natural ecosystems we conclude that diffusion variability within populations is a significant driving force for the emergence of spatiotemporal patterns. Our results offer a perspective on self-organized phenomena, and pave a way to understand such phenomena in systems organized as complex ecological networks.

Tau and β-Amyloid Are Associated with Medial Temporal Lobe Structure, Function, and Memory Encoding in Normal Aging

PubMed Central

2017-01-01

Normal aging is associated with a decline in episodic memory and also with aggregation of the β-amyloid (Aβ) and tau proteins and atrophy of medial temporal lobe (MTL) structures crucial to memory formation. Although some evidence suggests that Aβ is associated with aberrant neural activity, the relationships among these two aggregated proteins, neural function, and brain structure are poorly understood. Using in vivo human Aβ and tau imaging, we demonstrate that increased Aβ and tau are both associated with aberrant fMRI activity in the MTL during memory encoding in cognitively normal older adults. This pathological neural activity was in turn associated with worse memory performance and atrophy within the MTL. A mediation analysis revealed that the relationship with regional atrophy was explained by MTL tau. These findings broaden the concept of cognitive aging to include evidence of Alzheimer's disease-related protein aggregation as an underlying mechanism of age-related memory impairment. SIGNIFICANCE STATEMENT Alterations in episodic memory and the accumulation of Alzheimer's pathology are common in cognitively normal older adults. However, evidence of pathological effects on episodic memory has largely been limited to β-amyloid (Aβ). Because Aβ and tau often cooccur in older adults, previous research offers an incomplete understanding of the relationship between pathology and episodic memory. With the recent development of in vivo tau PET radiotracers, we show that Aβ and tau are associated with different aspects of memory encoding, leading to aberrant neural activity that is behaviorally detrimental. In addition, our results provide evidence linking Aβ- and tau-associated neural dysfunction to brain atrophy. PMID:28213439

Detecting independent and recurrent copy number aberrations using interval graphs.

PubMed

Wu, Hsin-Ta; Hajirasouliha, Iman; Raphael, Benjamin J

2014-06-15

Somatic copy number aberrations SCNAS: are frequent in cancer genomes, but many of these are random, passenger events. A common strategy to distinguish functional aberrations from passengers is to identify those aberrations that are recurrent across multiple samples. However, the extensive variability in the length and position of SCNA: s makes the problem of identifying recurrent aberrations notoriously difficult. We introduce a combinatorial approach to the problem of identifying independent and recurrent SCNA: s, focusing on the key challenging of separating the overlaps in aberrations across individuals into independent events. We derive independent and recurrent SCNA: s as maximal cliques in an interval graph constructed from overlaps between aberrations. We efficiently enumerate all such cliques, and derive a dynamic programming algorithm to find an optimal selection of non-overlapping cliques, resulting in a very fast algorithm, which we call RAIG (Recurrent Aberrations from Interval Graphs). We show that RAIG outperforms other methods on simulated data and also performs well on data from three cancer types from The Cancer Genome Atlas (TCGA). In contrast to existing approaches that employ various heuristics to select independent aberrations, RAIG optimizes a well-defined objective function. We show that this allows RAIG to identify rare aberrations that are likely functional, but are obscured by overlaps with larger passenger aberrations. http://compbio.cs.brown.edu/software. © The Author 2014. Published by Oxford University Press.

An adaptive spatio-temporal Gaussian filter for processing cardiac optical mapping data.

PubMed

Pollnow, S; Pilia, N; Schwaderlapp, G; Loewe, A; Dössel, O; Lenis, G

2018-06-04

Optical mapping is widely used as a tool to investigate cardiac electrophysiology in ex vivo preparations. Digital filtering of fluorescence-optical data is an important requirement for robust subsequent data analysis and still a challenge when processing data acquired from thin mammalian myocardium. Therefore, we propose and investigate the use of an adaptive spatio-temporal Gaussian filter for processing optical mapping signals from these kinds of tissue usually having low signal-to-noise ratio (SNR). We demonstrate how filtering parameters can be chosen automatically without additional user input. For systematic comparison of this filter with standard filtering methods from the literature, we generated synthetic signals representing optical recordings from atrial myocardium of a rat heart with varying SNR. Furthermore, all filter methods were applied to experimental data from an ex vivo setup. Our developed filter outperformed the other filter methods regarding local activation time detection at SNRs smaller than 3 dB which are typical noise ratios expected in these signals. At higher SNRs, the proposed filter performed slightly worse than the methods from literature. In conclusion, the proposed adaptive spatio-temporal Gaussian filter is an appropriate tool for investigating fluorescence-optical data with low SNR. The spatio-temporal filter parameters were automatically adapted in contrast to the other investigated filters. Copyright © 2018 Elsevier Ltd. All rights reserved.

Monitoring the Spatiotemporal Activities of miRNAs in Small Animal Models Using Molecular Imaging Modalities

PubMed Central

Baril, Patrick; Ezzine, Safia; Pichon, Chantal

2015-01-01

MicroRNAs (miRNAs) are a class of small non-coding RNAs that regulate gene expression by binding mRNA targets via sequence complementary inducing translational repression and/or mRNA degradation. A current challenge in the field of miRNA biology is to understand the functionality of miRNAs under physiopathological conditions. Recent evidence indicates that miRNA expression is more complex than simple regulation at the transcriptional level. MiRNAs undergo complex post-transcriptional regulations such miRNA processing, editing, accumulation and re-cycling within P-bodies. They are dynamically regulated and have a well-orchestrated spatiotemporal localization pattern. Real-time and spatio-temporal analyses of miRNA expression are difficult to evaluate and often underestimated. Therefore, important information connecting miRNA expression and function can be lost. Conventional miRNA profiling methods such as Northern blot, real-time PCR, microarray, in situ hybridization and deep sequencing continue to contribute to our knowledge of miRNA biology. However, these methods can seldom shed light on the spatiotemporal organization and function of miRNAs in real-time. Non-invasive molecular imaging methods have the potential to address these issues and are thus attracting increasing attention. This paper reviews the state-of-the-art of methods used to detect miRNAs and discusses their contribution in the emerging field of miRNA biology and therapy. PMID:25749473

Monitoring the spatiotemporal activities of miRNAs in small animal models using molecular imaging modalities.

PubMed

Baril, Patrick; Ezzine, Safia; Pichon, Chantal

2015-03-04

MicroRNAs (miRNAs) are a class of small non-coding RNAs that regulate gene expression by binding mRNA targets via sequence complementary inducing translational repression and/or mRNA degradation. A current challenge in the field of miRNA biology is to understand the functionality of miRNAs under physiopathological conditions. Recent evidence indicates that miRNA expression is more complex than simple regulation at the transcriptional level. MiRNAs undergo complex post-transcriptional regulations such miRNA processing, editing, accumulation and re-cycling within P-bodies. They are dynamically regulated and have a well-orchestrated spatiotemporal localization pattern. Real-time and spatio-temporal analyses of miRNA expression are difficult to evaluate and often underestimated. Therefore, important information connecting miRNA expression and function can be lost. Conventional miRNA profiling methods such as Northern blot, real-time PCR, microarray, in situ hybridization and deep sequencing continue to contribute to our knowledge of miRNA biology. However, these methods can seldom shed light on the spatiotemporal organization and function of miRNAs in real-time. Non-invasive molecular imaging methods have the potential to address these issues and are thus attracting increasing attention. This paper reviews the state-of-the-art of methods used to detect miRNAs and discusses their contribution in the emerging field of miRNA biology and therapy.

Altered Brain Activity in Unipolar Depression Revisited: Meta-analyses of Neuroimaging Studies.

PubMed

Müller, Veronika I; Cieslik, Edna C; Serbanescu, Ilinca; Laird, Angela R; Fox, Peter T; Eickhoff, Simon B

2017-01-01

During the past 20 years, numerous neuroimaging experiments have investigated aberrant brain activation during cognitive and emotional processing in patients with unipolar depression (UD). The results of those investigations, however, vary considerably; moreover, previous meta-analyses also yielded inconsistent findings. To readdress aberrant brain activation in UD as evidenced by neuroimaging experiments on cognitive and/or emotional processing. Neuroimaging experiments published from January 1, 1997, to October 1, 2015, were identified by a literature search of PubMed, Web of Science, and Google Scholar using different combinations of the terms fMRI (functional magnetic resonance imaging), PET (positron emission tomography), neural, major depression, depression, major depressive disorder, unipolar depression, dysthymia, emotion, emotional, affective, cognitive, task, memory, working memory, inhibition, control, n-back, and Stroop. Neuroimaging experiments (using fMRI or PET) reporting whole-brain results of group comparisons between adults with UD and healthy control individuals as coordinates in a standard anatomic reference space and using an emotional or/and cognitive challenging task were selected. Coordinates reported to show significant activation differences between UD and healthy controls during emotional or cognitive processing were extracted. By using the revised activation likelihood estimation algorithm, different meta-analyses were calculated. Meta-analyses tested for brain regions consistently found to show aberrant brain activation in UD compared with controls. Analyses were calculated across all emotional processing experiments, all cognitive processing experiments, positive emotion processing, negative emotion processing, experiments using emotional face stimuli, experiments with a sex discrimination task, and memory processing. All meta-analyses were calculated across experiments independent of reporting an increase or decrease of activity in major depressive disorder. For meta-analyses with a minimum of 17 experiments available, separate analyses were performed for increases and decreases. In total, 57 studies with 99 individual neuroimaging experiments comprising in total 1058 patients were included; 34 of them tested cognitive and 65 emotional processing. Overall analyses across cognitive processing experiments (P > .29) and across emotional processing experiments (P > .47) revealed no significant results. Similarly, no convergence was found in analyses investigating positive (all P > .15), negative (all P > .76), or memory (all P > .48) processes. Analyses that restricted inclusion of confounds (eg, medication, comorbidity, age) did not change the results. Inconsistencies exist across individual experiments investigating aberrant brain activity in UD and replication problems across previous neuroimaging meta-analyses. For individual experiments, these inconsistencies may relate to use of uncorrected inference procedures, differences in experimental design and contrasts, or heterogeneous clinical populations; meta-analytically, differences may be attributable to varying inclusion and exclusion criteria or rather liberal statistical inference approaches.

Altered Brain Activity in Unipolar Depression Revisited Meta-analyses of Neuroimaging Studies

PubMed Central

Müller, Veronika I.; Cieslik, Edna C.; Serbanescu, Ilinca; Laird, Angela R.; Fox, Peter T.; Eickhoff, Simon B.

2017-01-01

IMPORTANCE During the past 20 years, numerous neuroimaging experiments have investigated aberrant brain activation during cognitive and emotional processing in patients with unipolar depression (UD). The results of those investigations, however, vary considerably; moreover, previous meta-analyses also yielded inconsistent findings. OBJECTIVE To readdress aberrant brain activation in UD as evidenced by neuroimaging experiments on cognitive and/or emotional processing. DATA SOURCES Neuroimaging experiments published from January 1, 1997, to October 1, 2015, were identified by a literature search of PubMed, Web of Science, and Google Scholar using different combinations of the terms fMRI (functional magnetic resonance imaging), PET (positron emission tomography), neural, major depression, depression, major depressive disorder, unipolar depression, dysthymia, emotion, emotional, affective, cognitive, task, memory, working memory, inhibition, control, n-back, and Stroop. STUDY SELECTION Neuroimaging experiments (using fMRI or PET) reporting whole-brain results of group comparisons between adults with UD and healthy control individuals as coordinates in a standard anatomic reference space and using an emotional or/and cognitive challenging task were selected. DATA EXTRACTION AND SYNTHESIS Coordinates reported to show significant activation differences between UD and healthy controls during emotional or cognitive processing were extracted. By using the revised activation likelihood estimation algorithm, different meta-analyses were calculated. MAIN OUTCOMES AND MEASURES Meta-analyses tested for brain regions consistently found to show aberrant brain activation in UD compared with controls. Analyses were calculated across all emotional processing experiments, all cognitive processing experiments, positive emotion processing, negative emotion processing, experiments using emotional face stimuli, experiments with a sex discrimination task, and memory processing. All meta-analyses were calculated across experiments independent of reporting an increase or decrease of activity in major depressive disorder. For meta-analyses with a minimum of 17 experiments available, separate analyses were performed for increases and decreases. RESULTS In total, 57 studies with 99 individual neuroimaging experiments comprising in total 1058 patients were included; 34 of them tested cognitive and 65 emotional processing. Overall analyses across cognitive processing experiments (P > .29) and across emotional processing experiments (P > .47) revealed no significant results. Similarly, no convergence was found in analyses investigating positive (all P > .15), negative (all P > .76), or memory (all P > .48) processes. Analyses that restricted inclusion of confounds (eg, medication, comorbidity, age) did not change the results. CONCLUSIONS AND RELEVANCE Inconsistencies exist across individual experiments investigating aberrant brain activity in UD and replication problems across previous neuroimaging meta-analyses. For individual experiments, these inconsistencies may relate to use of uncorrected inference procedures, differences in experimental design and contrasts, or heterogeneous clinical populations; meta-analytically, differences may be attributable to varying inclusion and exclusion criteria or rather liberal statistical inference approaches. PMID:27829086

An analysis of current source density profiles activated by local stimulation in the mouse auditory cortex in vitro.

PubMed

Yamamura, Daiki; Sano, Ayaka; Tateno, Takashi

2017-03-15

To examine local network properties of the mouse auditory cortex in vitro, we recorded extracellular spatiotemporal laminar profiles driven by short electric local stimulation on a planar multielectrode array substrate. The recorded local field potentials were subsequently evaluated using current source density (CSD) analysis to identify sources and sinks. Current sinks are thought to be an indicator of net synaptic current in the small volume of cortex surrounding the recording site. Thus, CSD analysis combined with multielectrode arrays enabled us to compare mean synaptic activity in response to small current stimuli on a layer-by-layer basis. We also used senescence-accelerated mice (SAM), some strains of which show earlier onset of age-related hearing loss, to examine the characteristic spatiotemporal CSD profiles stimulated by electrodes in specific cortical layers. Thus, the CSD patterns were classified into several clusters based on stimulation sites in the cortical layers. We also found some differences in CSD patterns between the two SAM strains in terms of aging according to principle component analysis with dimension reduction. For simultaneous two-site stimulation, we modeled the obtained CSD profiles as a linear superposition of the CSD profiles to individual single-site stimulation. The model analysis indicated the nonlinearity of spatiotemporal integration over stimulus-driven activity in a layer-specific manner. Finally, on the basis of these results, we discuss the auditory cortex local network properties and the effects of aging on these mouse strains. Copyright © 2017 Elsevier B.V. All rights reserved.

NIR-induced spatiotemporally controlled gene silencing by upconversion nanoparticle-based siRNA nanocarrier.

PubMed

Chen, Guojun; Ma, Ben; Xie, Ruosen; Wang, Yuyuan; Dou, Kefeng; Gong, Shaoqin

2017-12-27

Spatiotemporal control over the release or activation of biomacromolecules such as siRNA remains a significant challenge. Light-controlled release has gained popularity in recent years; however, a major limitation is that most photoactivable compounds/systems respond only to UV irradiation, but not near-infrared (NIR) light that offers a deeper tissue penetration depth and better biocompatibility. This paper reports a simple NIR-to-UV upconversion nanoparticle (UCNP)-based siRNA nanocarrier for NIR-controlled gene silencing. siRNA is complexed onto a NaYF 4 :Yb/Tm/Er UCNP through an azobenzene (Azo)-cyclodextrin (CD) host-guest interaction. The UV emission generated by the NIR-activated UCNP effectively triggers the trans-to-cis photoisomerization of azobenzene, thus leading to the release of siRNA due to unmatched host-guest pairs. The UCNP-siRNA complexes are also functionalized with PEG (i.e., UCNP-(CD/Azo)-siRNA/PEG NPs), targeting ligands (i.e., EGFR-specific GE11 peptide), acid-activatable cell-penetrating peptides (i.e., TH peptide), and imaging probes (i.e., Cy5 fluorophore). The UCNP-(CD/Azo)-siRNA/PEG NPs with both GE11 and TH peptides display a high level of cellular uptake and an excellent endosomal/lysosomal escape capability. More importantly, NIR-controlled spatiotemporal knockdown of GFP expression is successfully achieved in both a 2D monolayer cell model and a 3D multicellular tumor spheroid model. Thus, this simple and versatile nanoplatform has great potential for the selective activation or release of various biomacromolecules. Copyright © 2017. Published by Elsevier B.V.

Targeted Cancer Therapy: Vital Oncogenes and a New Molecular Genetic Paradigm for Cancer Initiation Progression and Treatment.

PubMed

Willis, Rudolph E

2016-09-14

It has been declared repeatedly that cancer is a result of molecular genetic abnormalities. However, there has been no working model describing the specific functional consequences of the deranged genomic processes that result in the initiation and propagation of the cancer process during carcinogenesis. We no longer need to question whether or not cancer arises as a result of a molecular genetic defect within the cancer cell. The legitimate questions are: how and why? This article reviews the preeminent data on cancer molecular genetics and subsequently proposes that the sentinel event in cancer initiation is the aberrant production of fused transcription activators with new molecular properties within normal tissue stem cells. This results in the production of vital oncogenes with dysfunctional gene activation transcription properties, which leads to dysfunctional gene regulation, the aberrant activation of transduction pathways, chromosomal breakage, activation of driver oncogenes, reactivation of stem cell transduction pathways and the activation of genes that result in the hallmarks of cancer. Furthermore, a novel holistic molecular genetic model of cancer initiation and progression is presented along with a new paradigm for the approach to personalized targeted cancer therapy, clinical monitoring and cancer diagnosis.

Aberrant temporal and spatial brain activity during rest in patients with chronic pain

PubMed Central

Malinen, Sanna; Vartiainen, Nuutti; Hlushchuk, Yevhen; Koskinen, Miika; Ramkumar, Pavan; Forss, Nina; Kalso, Eija; Hari, Riitta

2010-01-01

In the absence of external stimuli, human hemodynamic brain activity displays slow intrinsic variations. To find out whether such fluctuations would be altered by persistent pain, we asked 10 patients with unrelenting chronic pain of different etiologies and 10 sex- and age-matched control subjects to rest with eyes open during 3-T functional MRI. Independent component analysis was used to identify functionally coupled brain networks. Time courses of an independent component comprising the insular cortices of both hemispheres showed stronger spectral power at 0.12 to 0.25 Hz in patients than in control subjects, with the largest difference at 0.16 Hz. A similar but weaker effect was seen in the anterior cingulate cortex, whereas activity of the precuneus and early visual cortex, used as a control site, did not differ between the groups. In the patient group, seed point-based correlation analysis revealed altered spatial connectivity between insulae and anterior cingulate cortex. The results imply both temporally and spatially aberrant activity of the affective pain-processing areas in patients suffering from chronic pain. The accentuated 0.12- to 0.25-Hz fluctuations in the patient group might be related to altered activity of the autonomic nervous system. PMID:20308545

Sources of the monochromatic aberrations induced in human eyes after laser refractive surgery

NASA Astrophysics Data System (ADS)

Porter, Jason

Laser in-situ keratomileusis (LASIK) procedures correct the eye's defocus and astigmatism but also introduce higher order monochromatic aberrations. Little is known about the origins of these induced aberrations. The advent of wavefront sensor technology has made it possible to measure accurately and quickly the aberrations of normal and postoperative LASIK eyes. The goal of this thesis was to exploit this technology to better understand some of the potential mechanisms by which aberrations could be introduced during LASIK. A first step towards investigating these sources was to characterize the aberration changes in post-LASIK eyes. Higher order rms wavefront error increased after conventional and customized LASIK surgery. On average, spherical aberration approximately doubled, and significant changes in vertical and horizontal coma were observed. We examined two sources of postoperative aberrations: the creation of a microkeratome flap and the subsequent laser ablation. Higher order rms increased slightly and there was a wide variation in the response of individual Zernike modes after cutting a flap. The majority of induced spherical aberration was due to the laser ablation and not the flap-cut. Aberrations are also induced by static and dynamic decentrations of the patient's pupil. We found that ablations were typically decentered in the superotemporal direction due to shifts in pupil center location between aberration measurement (dilated) and surgical (undilated) conditions in customized LASIK eyes. There was a weak correlation between the horizontal coma theoretically induced by this offset and that measured postoperatively. Finally, dynamic eye movements during the procedure induce higher order aberrations. We found that the most problematic decentrations during LASIK are relatively slow drifts in eye position. An eye-tracking system with a 2-Hz closed-loop bandwidth could compensate for most eye movements during LASIK. One solution for reducing the aberrations induced by static and dynamic shifts in pupil center location is to reference the aberration measurement and treatment with respect to fixed features on the eye. Several other sources of aberration induction in LASIK, such as the efficiency of laser pulses striking the cornea perpendicularly versus obliquely, must still be investigated to optimize postoperative optical quality after LASIK.

Curvature wavefront sensing performance evaluation for active correction of the Large Synoptic Survey Telescope (LSST).

PubMed

Manuel, Anastacia M; Phillion, Donald W; Olivier, Scot S; Baker, Kevin L; Cannon, Brice

2010-01-18

The Large Synoptic Survey Telescope (LSST) uses a novel, three-mirror, modified Paul-Baker design, with an 8.4-meter primary mirror, a 3.4-m secondary, and a 5.0-m tertiary, along with three refractive corrector lenses to produce a flat focal plane with a field of view of 9.6 square degrees. In order to maintain image quality during operation, the deformations and rigid body motions of the three large mirrors must be actively controlled to minimize optical aberrations, which arise primarily from forces due to gravity and thermal expansion. We describe the methodology for measuring the telescope aberrations using a set of curvature wavefront sensors located in the four corners of the LSST camera focal plane. We present a comprehensive analysis of the wavefront sensing system, including the availability of reference stars, demonstrating that this system will perform to the specifications required to meet the LSST performance goals.

Spatiotemporal brain dynamics of emotional face processing modulations induced by the serotonin 1A/2A receptor agonist psilocybin.

PubMed

Bernasconi, Fosco; Schmidt, André; Pokorny, Thomas; Kometer, Michael; Seifritz, Erich; Vollenweider, Franz X

2014-12-01

Emotional face processing is critically modulated by the serotonergic system. For instance, emotional face processing is impaired by acute psilocybin administration, a serotonin (5-HT) 1A and 2A receptor agonist. However, the spatiotemporal brain mechanisms underlying these modulations are poorly understood. Here, we investigated the spatiotemporal brain dynamics underlying psilocybin-induced modulations during emotional face processing. Electrical neuroimaging analyses were applied to visual evoked potentials in response to emotional faces, following psilocybin and placebo administration. Our results indicate a first time period of strength (i.e., Global Field Power) modulation over the 168-189 ms poststimulus interval, induced by psilocybin. A second time period of strength modulation was identified over the 211-242 ms poststimulus interval. Source estimations over these 2 time periods further revealed decreased activity in response to both neutral and fearful faces within limbic areas, including amygdala and parahippocampal gyrus, and the right temporal cortex over the 168-189 ms interval, and reduced activity in response to happy faces within limbic and right temporo-occipital brain areas over the 211-242 ms interval. Our results indicate a selective and temporally dissociable effect of psilocybin on the neuronal correlates of emotional face processing, consistent with a modulation of the top-down control. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

On- and off-eye spherical aberration of soft contact lenses and consequent changes of effective lens power.

PubMed

Dietze, Holger H; Cox, Michael J

2003-02-01

Soft contact lenses produce a significant level of spherical aberration affecting their power on-eye. A simple model assuming that a thin soft contact lens aligns to the cornea predicts that these effects are similar on-eye and off-eye. The wavefront aberration for 17 eyes and 33 soft contact lenses on-eye was measured with a Shack-Hartmann wavefront sensor. The Zernike coefficients describing the on-eye spherical aberration of the soft contact lens were compared with off-eye ray-tracing results. Paraxial and effective lens power changes were determined. The model predicts the on-eye spherical aberration of soft contact lenses closely. The resulting power change for a +/- 7.00 D spherical soft contact lens is +/- 0.5 D for a 6-mm pupil diameter and +/- 0.1 D for a 3-mm pupil diameter. Power change is negligible for soft contact lenses corrected for off-eye spherical aberration. For thin soft contact lenses, the level of spherical aberration and the consequent power change is similar on-eye and off-eye. Soft contact lenses corrected for spherical aberration in air will be expected to be aberration-free on-eye and produce only negligibly small power changes. For soft contact lenses without aberration correction, for higher levels of ametropia and large pupils, the soft contact lens power should be determined with trial lenses with their power and p value similar to the prescribed lens. The benefit of soft contact lenses corrected for spherical aberration depends on the level of ocular spherical aberration.

An event-version-based spatio-temporal modeling approach and its application in the cadastral management

NASA Astrophysics Data System (ADS)

Li, Yangdong; Han, Zhen; Liao, Zhongping

2009-10-01

Spatiality, temporality, legality, accuracy and continuality are characteristic of cadastral information, and the cadastral management demands that the cadastral data should be accurate, integrated and updated timely. It's a good idea to build an effective GIS management system to manage the cadastral data which are characterized by spatiality and temporality. Because no sound spatio-temporal data models have been adopted, however, the spatio-temporal characteristics of cadastral data are not well expressed in the existing cadastral management systems. An event-version-based spatio-temporal modeling approach is first proposed from the angle of event and version. Then with the help of it, an event-version-based spatio-temporal cadastral data model is built to represent spatio-temporal cadastral data. At last, the previous model is used in the design and implementation of a spatio-temporal cadastral management system. The result of the application of the system shows that the event-version-based spatio-temporal data model is very suitable for the representation and organization of cadastral data.

Classification of motor intent in transradial amputees using sonomyography and spatio-temporal image analysis

NASA Astrophysics Data System (ADS)

Hariharan, Harishwaran; Aklaghi, Nima; Baker, Clayton A.; Rangwala, Huzefa; Kosecka, Jana; Sikdar, Siddhartha

2016-04-01

In spite of major advances in biomechanical design of upper extremity prosthetics, these devices continue to lack intuitive control. Conventional myoelectric control strategies typically utilize electromyography (EMG) signal amplitude sensed from forearm muscles. EMG has limited specificity in resolving deep muscle activity and poor signal-to-noise ratio. We have been investigating alternative control strategies that rely on real-time ultrasound imaging that can overcome many of the limitations of EMG. In this work, we present an ultrasound image sequence classification method that utilizes spatiotemporal features to describe muscle activity and classify motor intent. Ultrasound images of the forearm muscles were obtained from able-bodied subjects and a trans-radial amputee while they attempted different hand movements. A grid-based approach is used to test the feasibility of using spatio-temporal features by classifying hand motions performed by the subjects. Using the leave-one-out cross validation on image sequences acquired from able-bodied subjects, we observe that the grid-based approach is able to discern four hand motions with 95.31% accuracy. In case of the trans-radial amputee, we are able to discern three hand motions with 80% accuracy. In a second set of experiments, we study classification accuracy by extracting spatio-temporal sub-sequences the depict activity due to the motion of local anatomical interfaces. Short time and space limited cuboidal sequences are initially extracted and assigned an optical flow behavior label, based on a response function. The image space is clustered based on the location of cuboids and features calculated from the cuboids in each cluster. Using sequences of known motions, we extract feature vectors that describe said motion. A K-nearest neighbor classifier is designed for classification experiments. Using the leave-one-out cross validation on image sequences for an amputee subject, we demonstrate that the classifier is able to discern three important hand motions with an accuracy of 93.33% accuracy, 91-100% precision and 80-100% recall rate. We anticipate that ultrasound imaging based methods will address some limitations of conventional myoelectric sensing, while adding advantages inherent to ultrasound imaging.

Aberrated laser beams in terms of Zernike polynomials

NASA Astrophysics Data System (ADS)

Alda, Javier; Alonso, Jose; Bernabeu, Eusebio

1996-11-01

The characterization of light beams has devoted a lot of attention in the past decade. Several formalisms have been presented to treat the problem of parameter invariance and characterization in the propagation of light beam along ideal, ABCD, optical systems. The hard and soft apertured optical systems have been treated too. Also some aberrations have been analyzed, but it has not appeared a formalism able to treat the problem as a whole. In this contribution we use a classical approach to describe the problem of aberrated, and therefore apertured, light beams. The wavefront aberration is included in a pure phase term expanded in terms of the Zernike polynomials. Then, we can use the relation between the lower order Zernike polynomia and the Seidel or third order aberrations. We analyze the astigmatism, the spherical aberration and the coma, and we show how higher order aberrations can be taken into account. We have calculated the divergence, and the radius of curvature of such aberrated beams and the influence of these aberrations in the quality of the light beam. Some numerical simulations have been done to illustrate the method.

Microscale Spatiotemporal Dynamics during Neocortical Propagation of Human Focal Seizures

PubMed Central

Wagner, Fabien B.; Eskandar, Emad N.; Cosgrove, G. Rees; Madsen, Joseph R.; Blum, Andrew S.; Potter, N. Stevenson; Hochberg, Leigh R.; Cash, Sydney S.; Truccolo, Wilson

2015-01-01

Some of the most clinically consequential aspects of focal epilepsy, e.g. loss of consciousness, arise from the generalization or propagation of seizures through local and large-scale neocortical networks. Yet, the dynamics of such neocortical propagation remain poorly understood. Here, we studied the microdynamics of focal seizure propagation in neocortical patches (4 × 4 mm) recorded via high-density microelectrode arrays (MEAs) implanted in people with pharmacologically resistant epilepsy. Our main findings are threefold: (1) A newly developed stage segmentation method, applied to local field potentials (LFPs) and multi-unit activity (MUA), revealed a succession of discrete seizure stages, each lasting several seconds. These different stages showed characteristic evolutions in overall activity and spatial patterns, which were relatively consistent across seizures within each of the 5 patients studied. Interestingly, segmented seizure stages based on LFPs or MUA showed a dissociation of their spatiotemporal dynamics, likely reflecting different contributions of non-local synaptic inputs and local network activity. (2) As previously reported, some of the seizures showed a peak in MUA that happened several seconds after local seizure onset and slowly propagated across the MEA. However, other seizures had a more complex structure characterized by, for example, several MUA peaks, more consistent with the succession of discrete stages than the slow propagation of a simple wavefront of increased MUA. In both cases, nevertheless, seizures characterized by spike-wave discharges (SWDs, ~ 2–3Hz) eventually evolved into patterns of phase-locked MUA and LFPs. (3) Individual SWDs or gamma oscillation cycles (25–60 Hz), characteristic of two different types of recorded seizures, tended to propagate with varying degrees of directionality, directions of propagation and speeds, depending on the identified seizure stage. However, no clear relationship was observed between the MUA peak onset time (in seizures where such peak onset occurred) and changes in MUA or LFP propagation patterns. Overall, our findings indicate that the recruitment of neocortical territories into ictal activity undergo complex spatiotemporal dynamics evolving in slow discrete states, which are consistent across seizures within each patient. Furthermore, ictal states at finer spatiotemporal scales (individual SWDs or gamma oscillations) are organized by slower time-scale network dynamics evolving through these discrete stages. PMID:26279211

Imaging of early acceleration phase of the 2013-2014 Boso slow slip event

NASA Astrophysics Data System (ADS)

Fukuda, J.; Kato, A.; Obara, K.; Miura, S.; Kato, T.

2014-12-01

Based on GPS and seismic data, we examine the spatiotemporal evolution of a slow slip event (SSE) and associated seismic activity that occurred off the Boso peninsula, central Japan, from December 2013 to January 2014. We use GPS data from 71 stations of the GEONET and 6 stations operated by Earthquake Research Institute of the University of Tokyo and Tohoku University around the Boso peninsula. We apply a modified version of the Network Inversion Filter to the GPS time series at the 77 stations to estimate the spatiotemporal evolution of daily cumulative slip and slip rate on the subducting Philippine Sea plate. In addition, we create an improved earthquake catalog by applying a matched filter technique to continuous seismograms and examine the spatiotemporal relations between slow slip and seismicity. We find that the SSE started in early December 2013. The spatiotemporal evolution of slow slip and seismicity is divided into two distinct phases, an earlier slow phase from early to 30 December 2013 (Phase I) and a subsequent faster phase from 30 December 2013 to 9 January 2014 (Phase II). During Phase I, slip accelerated slowly up to a maximum rate of 1.6 m/yr with potentially accelerating　along-strike propagation at speeds on the order of 1 km/day or less and no accompanying seismicity. On the other hand, during Phase II, slip accelerated rapidly up to a maximum rate of 4.5 m/yr and then rapidly decelerated. The slip front propagated along strike at a constant speed of ~10 km/day. During the Phase II, slow slip was accompanied by seismic swarm activity that was highly correlated in space and time with slip rate, suggesting that the swarm activity was triggered by stress loading due to slow slip. Early slow acceleration of slip has not been identified in the past Boso SSEs in 1996, 2002, 2007, and 2011. It is not clear at this point whether the past Boso SSEs started with slow acceleration similarly to the 2013-2014 SSE. The transition from the slow to the faster phase shares some similarities with the nucleation of megathrust earthquakes inferred from foreshock activities, suggesting that SSEs may provide insights into the nucleation of large earthquakes.

Prognostic Value of Molecular Markers and Implication for Molecular Targeted Therapies in Nasopharyngeal Carcinoma: An Update in an Era of New Targeted Molecules Development.

PubMed

Liu, Mu-Tai; Chen, Mu-Kuan; Huang, Chia-Chun; Huang, Chao-Yuan

2015-02-01

The aim of the study was to evaluate the prognostic significance of molecular biomarkers which could provide information for more accurate prognostication and development of novel therapeutic strategies for nasopharyngeal carcinoma (NPC). NPC is a unique malignant epithelial carcinoma of head and neck region, with an intimate association with the Epstein-Barr virus (EBV). Currently, the prediction of NPC prognosis is mainly based on the clinical TNM staging; however, NPC patients with the same clinical stage often present different clinical outcomes, suggesting that the TNM stage is insufficient to precisely predict the prognosis of this disease. In this review, we give an overview of the prognostic value of molecular markers in NPC and discuss potential strategies of targeted therapies for treatment of NPC. Molecular biomarkers, which play roles in abnormal proliferation signaling pathways (such as Wnt/β-catenin pathway), intracellular mitogenic signal aberration (such as hypoxia-inducible factor (HIF)-1α), receptor-mediated aberrations (such as vascular endothelial growth factor (VEGF)), tumor suppressors (such as p16 and p27 activity), cell cycle aberrations (such as cyclin D1 and cyclin E), cell adhesion aberrations (such as E-cadherin), apoptosis dysregualtion (such as survivin) and centromere aberration (centromere protein H), are prognostic markers for NPC. Plasma EBV DNA concentrations and EBV-encoded latent membrane proteins are also prognostic markers for NPC. Implication of molecular targeted therapies in NPC was discussed. Such therapies could have potential in combination with different cytotoxic agents to combat and eradicate tumor cells. In order to further improve overall survival for patients with loco-regionally advanced NPC, the development of innovative strategies, including prognostic molecular markers and molecular targeted agents is needed.

Signatures of post-zygotic structural genetic aberrations in the cells of histologically normal breast tissue that can predispose to sporadic breast cancer

PubMed Central

Forsberg, Lars A.; Rasi, Chiara; Pekar, Gyula; Davies, Hanna; Piotrowski, Arkadiusz; Absher, Devin; Razzaghian, Hamid Reza; Ambicka, Aleksandra; Halaszka, Krzysztof; Przewoźnik, Marcin; Kruczak, Anna; Mandava, Geeta; Pasupulati, Saichand; Hacker, Julia; Prakash, K. Reddy; Dasari, Ravi Chandra; Lau, Joey; Penagos-Tafurt, Nelly; Olofsson, Helena M.; Hallberg, Gunilla; Skotnicki, Piotr; Mituś, Jerzy; Skokowski, Jaroslaw; Jankowski, Michal; Śrutek, Ewa; Zegarski, Wojciech; Tiensuu Janson, Eva; Ryś, Janusz; Tot, Tibor; Dumanski, Jan P.

2015-01-01

Sporadic breast cancer (SBC) is a common disease without robust means of early risk prediction in the population. We studied 282 females with SBC, focusing on copy number aberrations in cancer-free breast tissue (uninvolved margin, UM) outside the primary tumor (PT). In total, 1162 UMs (1–14 per breast) were studied. Comparative analysis between UM(s), PT(s), and blood/skin from the same patient as a control is the core of the study design. We identified 108 patients with at least one aberrant UM, representing 38.3% of cases. Gains in gene copy number were the principal type of mutations in microscopically normal breast cells, suggesting that oncogenic activation of genes via increased gene copy number is a predominant mechanism for initiation of SBC pathogenesis. The gain of ERBB2, with overexpression of HER2 protein, was the most common aberration in normal cells. Five additional growth factor receptor genes (EGFR, FGFR1, IGF1R, LIFR, and NGFR) also showed recurrent gains, and these were occasionally present in combination with the gain of ERBB2. All the aberrations found in the normal breast cells were previously described in cancer literature, suggesting their causative, driving role in pathogenesis of SBC. We demonstrate that analysis of normal cells from cancer patients leads to identification of signatures that may increase risk of SBC and our results could influence the choice of surgical intervention to remove all predisposing cells. Early detection of copy number gains suggesting a predisposition toward cancer development, long before detectable tumors are formed, is a key to the anticipated shift into a preventive paradigm of personalized medicine for breast cancer. PMID:26430163

Clinical outcomes of wavefront-guided laser in situ keratomileusis: 6-month follow-up.

PubMed

Aizawa, Daisuke; Shimizu, Kimiya; Komatsu, Mari; Ito, Misae; Suzuki, Masanobu; Ohno, Koji; Uozato, Hiroshi

2003-08-01

To evaluate the clinical outcomes 6 months after wavefront-guided laser in situ keratomileusis (LASIK) for myopia in Japan. Department of Ophthalmology, Sanno Hospital, Tokyo, Japan. This prospective study comprised 22 eyes of 12 patients treated with wavefront-guided LASIK who were available for evaluation at 6 months. The mean patient age was 31.2 years +/- 8.4 (SD) (range 23 to 50 years), and the mean preoperative spherical equivalent refraction was -7.30 +/- 2.72 diopters (D) (range -2.75 to -11.88 D). In all cases, preoperative wavefront analysis was performed with a Hartmann-Shack aberrometer and the Technolas 217z flying-spot excimer laser system (Bausch & Lomb) was used with 1.0 mm and 2.0 mm spot sizes and an active eye tracker with a 120 Hz tracking rate. The clinical outcomes of wavefront-guided LASIK were evaluated in terms of safety, efficacy, predictability, stability, complications, and preoperative and postoperative aberrations. At 6 months, 10 eyes had no change in best spectacle-correct visual acuity and 10 gained 1 or more lines. The safety index was 1.11 and the efficacy index, 0.82. Slight undercorrections were observed in highly myopic eyes. In all eyes, the postoperative refraction tended slightly toward myopia for 3 months and stabilized after that. No complication such as epithelial ingrowth, diffuse lamellar keratitis, or infection was observed. Comparison of the preoperative and postoperative aberrations showed that 2nd-order aberrations decreased and higher-order aberrations increased. In the 3rd order, aberrations increased in the high-myopia group (-6.0 D or worse) and decreased in the low to moderate-myopia group (better than -6.0 D). Wavefront-guided LASIK was a good option for refractive surgery, although a longer follow-up in a larger study is required.

Whole eye wavefront aberrations in Mexican male subjects.

PubMed

Cantú, Roberto; Rosales, Marco A; Tepichín, Eduardo; Curioca, Andrée; Montes, Victor; Bonilla, Julio

2004-01-01

To analyze the characteristics, incidence, and appearance of wavefront aberrations in undilated, normal, unoperated eyes. Eighty-eight eyes of 44 healthy male Mexican subjects (mean age 25.32 years, range 18 to 36 yr) were divided into three groups based on uncorrected visual acuity of greater than or equal to 20/20, 20/30, or 20/40. UCVA measurements were obtained using an Acuity Max computer screen chart. Wavefront aberrations were measured with the Nidek OPD-Scan ARK 10000, Ver. 1.11b. All measurements were carried out at the same center by the same technician during a single session, following manufacturer instructions. Background illumination was 3 Lux. Wavefront aberration measurements for each group were statistically analyzed using StatView; an average eye was characterized and the resulting aberrations were simulated using MATLAB. We obtained wavefront aberration maps for the 20/20 undilated normal unoperated eyes for total, low, and high order aberration coefficients. Wavefront maps for right eyes were practically the same as those for left eyes. Higher aberrations did not contribute substantially to total wavefront analysis. Average aberrations of this "normal eye" will be used as criteria to decide the necessity of wavefront-guided ablation in our facilities. We will focus on the nearly zero average of high order aberrations in this normal whole eye as a reference to be matched.

Factors Affecting EWS-FLI1 Activity in Ewing's Sarcoma

PubMed Central

Herrero-Martin, David; Fourtouna, Argyro; Niedan, Stephan; Riedmann, Lucia T.; Schwentner, Raphaela; Aryee, Dave N. T.

2011-01-01

Ewing's sarcoma family tumors (ESFT) are characterized by specific chromosomal translocations, which give rise to EWS-ETS chimeric proteins. These aberrant transcription factors are the main pathogenic drivers of ESFT. Elucidation of the factors influencing EWS-ETS expression and/or activity will guide the development of novel therapeutic agents against this fatal disease. PMID:22135504

Design of Optical Systems with Extended Depth of Field: An Educational Approach to Wavefront Coding Techniques

ERIC Educational Resources Information Center

Ferran, C.; Bosch, S.; Carnicer, A.

2012-01-01

A practical activity designed to introduce wavefront coding techniques as a method to extend the depth of field in optical systems is presented. The activity is suitable for advanced undergraduate students since it combines different topics in optical engineering such as optical system design, aberration theory, Fourier optics, and digital image…

Spatiotemporal neurodynamics of automatic temporal expectancy in 9-month old infants.

PubMed

Mento, Giovanni; Valenza, Eloisa

2016-11-04

Anticipating events occurrence (Temporal Expectancy) is a crucial capacity for survival. Yet, there is little evidence about the presence of cortical anticipatory activity from infancy. In this study we recorded the High-density electrophysiological activity in 9 month-old infants and adults undergoing an audio-visual S1-S2 paradigm simulating a lifelike "Peekaboo" game inducing automatic temporal expectancy of smiling faces. The results indicate in the S2-preceding Contingent Negative Variation (CNV) an early electrophysiological signature of expectancy-based anticipatory cortical activity. Moreover, the progressive CNV amplitude increasing across the task suggested that implicit temporal rule learning is at the basis of expectancy building-up over time. Cortical source reconstruction suggested a common CNV generator between adults and infants in the right prefrontal cortex. The decrease in the activity of this area across the task (time-on-task effect) further implied an early, core role of this region in implicit temporal rule learning. By contrast, a time-on-task activity boost was found in the supplementary motor area (SMA) in adults and in the temporoparietal regions in infants. Altogether, our findings suggest that the capacity of the human brain to translate temporal predictions into anticipatory neural activity emerges ontogenetically early, although the underlying spatiotemporal cortical dynamics change across development.

4-dimensional functional profiling in the convulsant-treated larval zebrafish brain.

PubMed

Winter, Matthew J; Windell, Dylan; Metz, Jeremy; Matthews, Peter; Pinion, Joe; Brown, Jonathan T; Hetheridge, Malcolm J; Ball, Jonathan S; Owen, Stewart F; Redfern, Will S; Moger, Julian; Randall, Andrew D; Tyler, Charles R

2017-07-26

Functional neuroimaging, using genetically-encoded Ca 2+ sensors in larval zebrafish, offers a powerful combination of high spatiotemporal resolution and higher vertebrate relevance for quantitative neuropharmacological profiling. Here we use zebrafish larvae with pan-neuronal expression of GCaMP6s, combined with light sheet microscopy and a novel image processing pipeline, for the 4D profiling of chemoconvulsant action in multiple brain regions. In untreated larvae, regions associated with autonomic functionality, sensory processing and stress-responsiveness, consistently exhibited elevated spontaneous activity. The application of drugs targeting different convulsant mechanisms (4-Aminopyridine, Pentylenetetrazole, Pilocarpine and Strychnine) resulted in distinct spatiotemporal patterns of activity. These activity patterns showed some interesting parallels with what is known of the distribution of their respective molecular targets, but crucially also revealed system-wide neural circuit responses to stimulation or suppression. Drug concentration-response curves of neural activity were identified in a number of anatomically-defined zebrafish brain regions, and in vivo larval electrophysiology, also conducted in 4dpf larvae, provided additional measures of neural activity. Our quantification of network-wide chemoconvulsant drug activity in the whole zebrafish brain illustrates the power of this approach for neuropharmacological profiling in applications ranging from accelerating studies of drug safety and efficacy, to identifying pharmacologically-altered networks in zebrafish models of human neurological disorders.

A spatiotemporal profile of visual system activation revealed by current source density analysis in the awake macaque.

PubMed

Schroeder, C E; Mehta, A D; Givre, S J

1998-01-01

We investigated the spatiotemporal activation pattern, produced by one visual stimulus, across cerebral cortical regions in awake monkeys. Laminar profiles of postsynaptic potentials and action potentials were indexed with current source density (CSD) and multiunit activity profiles respectively. Locally, we found contrasting activation profiles in dorsal and ventral stream areas. The former, like V1 and V2, exhibit a 'feedforward' profile, with excitation beginning at the depth of Lamina 4, followed by activation of the extragranular laminae. The latter often displayed a multilaminar/columnar profile, with initial responses distributed across the laminae and reflecting modulation rather than excitation; CSD components were accompanied by either no changes or by suppression of action potentials. System-wide, response latencies indicated a large dorsal/ventral stream latency advantage, which generalizes across a wide range of methods. This predicts a specific temporal ordering of dorsal and ventral stream components of visual analysis, as well as specific patterns of dorsal-ventral stream interaction. Our findings support a hierarchical model of cortical organization that combines serial and parallel elements. Critical in such a model is the recognition that processing within a location typically entails multiple temporal components or 'waves' of activity, driven by input conveyed over heterogeneous pathways from the retina.

TGF-β mediates early angiogenesis and latent fibrosis in an Emilin1-deficient mouse model of aortic valve disease

PubMed Central

Munjal, Charu; Opoka, Amy M.; Osinska, Hanna; James, Jeanne F.; Bressan, Giorgio M.; Hinton, Robert B.

2014-01-01

Aortic valve disease (AVD) is characterized by elastic fiber fragmentation (EFF), fibrosis and aberrant angiogenesis. Emilin1 is an elastin-binding glycoprotein that regulates elastogenesis and inhibits TGF-β signaling, but the role of Emilin1 in valve tissue is unknown. We tested the hypothesis that Emilin1 deficiency results in AVD, mediated by non-canonical (MAPK/phosphorylated Erk1 and Erk2) TGF-β dysregulation. Using histology, immunohistochemistry, electron microscopy, quantitative gene expression analysis, immunoblotting and echocardiography, we examined the effects of Emilin1 deficiency (Emilin1−/−) in mouse aortic valve tissue. Emilin1 deficiency results in early postnatal cell-matrix defects in aortic valve tissue, including EFF, that progress to latent AVD and premature death. The Emilin1−/− aortic valve displays early aberrant provisional angiogenesis and late neovascularization. In addition, Emilin1−/− aortic valves are characterized by early valve interstitial cell activation and proliferation and late myofibroblast-like cell activation and fibrosis. Interestingly, canonical TGF-β signaling (phosphorylated Smad2 and Smad3) is upregulated constitutively from birth to senescence, whereas non-canonical TGF-β signaling (phosphorylated Erk1 and Erk2) progressively increases over time. Emilin1 deficiency recapitulates human fibrotic AVD, and advanced disease is mediated by non-canonical (MAPK/phosphorylated Erk1 and Erk2) TGF-β activation. The early manifestation of EFF and aberrant angiogenesis suggests that these processes are crucial intermediate factors involved in disease progression and therefore might provide new therapeutic targets for human AVD. PMID:25056700

Radiation-induced chromosomal instability in BALB/c and C57BL/6 mice: the difference is as clear as black and white

NASA Technical Reports Server (NTRS)

Ponnaiya, B.; Cornforth, M. N.; Ullrich, R. L.

1997-01-01

Genomic instability has been proposed to be the earliest step in radiation-induced tumorigenesis. It follows from this hypothesis that individuals highly susceptible to induction of tumors by radiation should exhibit enhanced radiation-induced instability. BALB/c white mice are considerably more sensitive to radiation-induced mammary cancer than C57BL/6 black mice. In this study, primary mammary epithelial cell cultures from these two strains were examined for the "delayed" appearance of chromosomal aberrations after exposure to 137Cs gamma radiation, as a measure of radiation-induced genomic instability. As expected, actively dividing cultures from both strains showed a rapid decline of initial asymmetrical aberrations with time postirradiation. However, after 16 population doublings, cells from BALB/c mice exhibited a marked increase in the frequency of chromatid-type breaks and gaps which remained elevated throughout the time course of the experiment (28 doublings). No such effect was observed for the cells of C57BL/6 mice; after the rapid clearance of initial aberrations, the frequency of chromatid-type aberrations in the irradiated population remained at or near those of nonirradiated controls. These results demonstrate a correlation between the latent expression of chromosomal damage in vitro and susceptibility for mammary tumors, and provide further support for the central role of radiation-induced instability in the process of tumorigenesis.

Computational and design methods for advanced imaging

NASA Astrophysics Data System (ADS)

Birch, Gabriel C.

This dissertation merges the optical design and computational aspects of imaging systems to create novel devices that solve engineering problems in optical science and attempts to expand the solution space available to the optical designer. This dissertation is divided into two parts: the first discusses a new active illumination depth sensing modality, while the second part discusses a passive illumination system called plenoptic, or lightfield, imaging. The new depth sensing modality introduced in part one is called depth through controlled aberration. This technique illuminates a target with a known, aberrated projected pattern and takes an image using a traditional, unmodified imaging system. Knowing how the added aberration in the projected pattern changes as a function of depth, we are able to quantitatively determine depth of a series of points from the camera. A major advantage this method permits is the ability for illumination and imaging axes to be coincident. Plenoptic cameras capture both spatial and angular data simultaneously. This dissertation present a new set of parameters that permit the design and comparison of plenoptic devices outside the traditionally published plenoptic 1.0 and plenoptic 2.0 configurations. Additionally, a series of engineering advancements are presented, including full system raytraces of raw plenoptic images, Zernike compression techniques of raw image files, and non-uniform lenslet arrays to compensate for plenoptic system aberrations. Finally, a new snapshot imaging spectrometer is proposed based off the plenoptic configuration.

Theory of aberration fields for general optical systems with freeform surfaces.

PubMed

Fuerschbach, Kyle; Rolland, Jannick P; Thompson, Kevin P

2014-11-03

This paper utilizes the framework of nodal aberration theory to describe the aberration field behavior that emerges in optical systems with freeform optical surfaces, particularly φ-polynomial surfaces, including Zernike polynomial surfaces, that lie anywhere in the optical system. If the freeform surface is located at the stop or pupil, the net aberration contribution of the freeform surface is field constant. As the freeform optical surface is displaced longitudinally away from the stop or pupil of the optical system, the net aberration contribution becomes field dependent. It is demonstrated that there are no new aberration types when describing the aberration fields that arise with the introduction of freeform optical surfaces. Significantly it is shown that the aberration fields that emerge with the inclusion of freeform surfaces in an optical system are exactly those that have been described by nodal aberration theory for tilted and decentered optical systems. The key contribution here lies in establishing the field dependence and nodal behavior of each freeform term that is essential knowledge for effective application to optical system design. With this development, the nodes that are distributed throughout the field of view for each aberration type can be anticipated and targeted during optimization for the correction or control of the aberrations in an optical system with freeform surfaces. This work does not place any symmetry constraints on the optical system, which could be packaged in a fully three dimensional geometry, without fold mirrors.

The role of ethnic identity, self-concept, and aberrant salience in psychotic-like experiences.

PubMed

Cicero, David C; Cohn, Jonathan R

2018-01-01

Social-cognitive models of psychosis suggest that aberrant salience and self-concept clarity are related to the development and maintenance of psychoticlike experiences (PLEs). People with high aberrant salience but low self-concept clarity tend to have the highest levels of PLEs. Ethnic identity may also be related to PLEs. The current research aimed to (a) replicate the interaction between aberrant salience and self-concept clarity in their association with PLEs in an ethnically diverse sample, (b) examine whether ethnic identity and aberrant salience interact in their association with PLEs, and (c) determine if self-concept clarity and ethnic identity independently interact with aberrant salience in their association with PLEs. An ethnically diverse group of undergraduates (n = 663) completed self-report measures of aberrant salience, self-concept clarity, ethnic identity, and PLEs. There was an interaction between aberrant salience and self-concept clarity such that people with high levels of aberrant salience and low levels of self-concept clarity had the highest levels of PLEs. Similarly, there was an interaction between aberrant salience and ethnic identity such that people with high aberrant salience but low ethnic identity had the highest PLEs. These interactions independently contributed to explaining variance in PLEs. This interaction was present for the Exploration but not Commitment subscales of ethnic identity. These results suggest that, in addition to low self-concept clarity, low ethnic identity may be a risk factor for the development of psychosis. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Characterization of New Otic Enhancers of the Pou3f4 Gene Reveal Distinct Signaling Pathway Regulation and Spatio-Temporal Patterns

PubMed Central

Robert-Moreno, Àlex; Naranjo, Silvia; de la Calle-Mustienes, Elisa; Gómez-Skarmeta, José Luis; Alsina, Berta

2010-01-01

POU3F4 is a member of the POU-homedomain transcription factor family with a prominent role in inner ear development. Mutations in the human POU3F4 coding unit leads to X-linked deafness type 3 (DFN3), characterized by conductive hearing loss and progressive sensorineural deafness. Microdeletions found 1 Mb 5′ upstream of the coding region also displayed the same phenotype, suggesting that cis-regulatory elements might be present in that region. Indeed, we and others have recently identified several enhancers at the 1 Mb 5′ upstream interval of the pou3f4 locus. Here we characterize the spatio-temporal patterns of these regulatory elements in zebrafish transgenic lines. We show that the most distal enhancer (HCNR 81675) is activated earlier and drives GFP reporter expression initially to a broad ear domain to progressively restrict to the sensory patches. The proximal enhancer (HCNR 82478) is switched later during development and promotes expression, among in other tissues, in sensory patches from its onset. The third enhancer (HCNR 81728) is also active at later stages in the otic mesenchyme and in the otic epithelium. We also characterize the signaling pathways regulating these enhancers. While HCNR 81675 is regulated by very early signals of retinoic acid, HCNR 82478 is regulated by Fgf activity at a later stage and the HCNR 81728 enhancer is under the control of Hh signaling. Finally, we show that Sox2 and Pax2 transcription factors are bound to HCNR 81675 genomic region during otic development and specific mutations to these transcription factor binding sites abrogates HCNR 81675 enhancer activity. Altogether, our results suggest that pou3f4 expression in inner ear might be under the control of distinct regulatory elements that fine-tune the spatio-temporal activity of this gene and provides novel data on the signaling mechanisms controlling pou3f4 function. PMID:21209840

Radiation-induced hematopoietic myelosuppression and genotoxicity get significantly countered by active principles of Podophyllum hexandrum: A study in strain 'A' mice.

PubMed

Verma, Savita; Gupta, Manju Lata

2015-01-01

To investigate the protective role of a novel formulation, prepared by a combination of three active principles isolated from Podophyllum hexandrum (G-002M), against radiation- mediated hematopoietic suppression and cytogenetic aberrations in lethally irradiated mice. G-002M, a combination of podophyllotoxin, podophyllotoxin-β-D glucoside and rutin, was administered intramuscularly in mice (- 1 h) to radiation (9 Gy) exposure. The animals were autopsied at different time intervals for further studies. Loss of bone marrow progenitor cells, altered myeloid/erythroid ratio, serum erythropoietin and pancytopenia in irradiated mice was found significantly (p < 0.001) ameliorated in G-002M pre-administered mice within 30 d. Bcl-2 (B-cell lymphoma 2) and BAX (Bcl-2-associated X) protein expression was also positively (p < 0.001) countered in these mice. Chromosomal aberrations in 30 d were found remarkably (p < 0.001) reduced in marrow of G-002M pretreated mice. Accelerated antioxidants, reduced DNA damage, stimulated lymphocyte proliferation and minimal cellular atrophy in spleen were some of the other key features observed in G-002M administered mice. Reduction in hematopoietic aplasia and chromosomal aberrations, besides, early recovery in bone marrow and spleen of G-002M pretreated mice, could be attributed to its free radical scavenging, DNA protecting and apoptotic proteins modulating ability against radiation.

Primary cilium suppression by SREBP1c involves distortion of vesicular trafficking by PLA2G3

PubMed Central

Gijs, Hannah Laura; Willemarck, Nicolas; Vanderhoydonc, Frank; Khan, Niamat Ali; Dehairs, Jonas; Derua, Rita; Waelkens, Etienne; Taketomi, Yoshitaka; Murakami, Makoto; Agostinis, Patrizia; Annaert, Wim; Swinnen, Johannes V.

2015-01-01

Distortion of primary cilium formation is increasingly recognized as a key event in many human pathologies. One of the underlying mechanisms involves aberrant activation of the lipogenic transcription factor sterol regulatory element–binding protein 1c (SREBP1c), as observed in cancer cells. To gain more insight into the molecular pathways by which SREBP1c suppresses primary ciliogenesis, we searched for overlap between known ciliogenesis regulators and targets of SREBP1. One of the candidate genes that was consistently up-regulated in cellular models of SREBP1c-induced cilium repression was phospholipase A2 group III (PLA2G3), a phospholipase that hydrolyzes the sn-2 position of glycerophospholipids. Use of RNA interference and a chemical inhibitor of PLA2G3 rescued SREBP1c-induced cilium repression. Cilium repression by SREBP1c and PLA2G3 involved alterations in endosomal recycling and vesicular transport toward the cilium, as revealed by aberrant transferrin and Rab11 localization, and was largely mediated by an increase in lysophosphatidylcholine and lysophosphatidylethanolamine levels. Together these findings indicate that aberrant activation of SREBP1c suppresses primary ciliogenesis by PLA2G3-mediated distortion of vesicular trafficking and suggest that PLA2G3 is a novel potential target to normalize ciliogenesis in SREBP1c-overexpressing cells, including cancer cells. PMID:25904332

Normalization of aberrant resting state functional connectivity in fibromyalgia patients following a three month physical exercise therapy

PubMed Central

Flodin, P.; Martinsen, S.; Mannerkorpi, K.; Löfgren, M.; Bileviciute-Ljungar, I.; Kosek, E.; Fransson, P.

2015-01-01

Physical exercise is one of the most efficient interventions to mitigate chronic pain symptoms in fibromyalgia (FM). However, little is known about the neurophysiological mechanisms mediating these effects. In this study we investigated resting-state connectivity using functional magnetic resonance imaging (fMRI) before and after a 15 week standardized exercise program supervised by physical therapists. Our aim was to gain an understanding of how physical exercise influences previously shown aberrant patterns of intrinsic brain activity in FM. Fourteen FM patients and eleven healthy controls successfully completed the physical exercise treatment. We investigated post- versus pre-treatment changes of brain connectivity, as well as changes in clinical symptoms in the patient group. FM patients reported improvements in symptom severity. Although several brain regions showed a treatment-related change in connectivity, only the connectivity between the right anterior insula and the left primary sensorimotor area was significantly more affected by the physical exercise among the fibromyalgia patients compared to healthy controls. Our results suggest that previously observed aberrant intrinsic brain connectivity patterns in FM are partly normalized by the physical exercise therapy. However, none of the observed normalizations in intrinsic brain connectivity were significantly correlated with symptom changes. Further studies conducted in larger cohorts are warranted to investigate the precise relationship between improvements in fibromyalgia symptoms and changes in intrinsic brain activity. PMID:26413476

RET is a potential tumor suppressor gene in colorectal cancer

PubMed Central

Luo, Yanxin; Tsuchiya, Karen D.; Park, Dong Il; Fausel, Rebecca; Kanngurn, Samornmas; Welcsh, Piri; Dzieciatkowski, Slavomir; Wang, Jianping; Grady, William M.

2012-01-01

Cancer arises as the consequence of mutations and epigenetic alterations that activate oncogenes and inactivate tumor suppressor genes. Through a genome-wide screen for methylated genes in colon neoplasms, we identified aberrantly methylated RET in colorectal cancer. RET, a transmembrane receptor tyrosine kinase and a receptor for the GDNF-family ligands, was one of the first oncogenes to be identified and has been shown to be an oncogene in thyroid cancer and pheochromocytoma. However, unexpectedly, we found RET is methylated in 27% of colon adenomas and in 63% of colorectal cancers, and now provide evidence that RET has tumor suppressor activity in colon cancer. The aberrant methylation of RET correlates with decreased RET expression, whereas the restoration of RET in colorectal cancer cell lines results in apoptosis. Furthermore, in support of a tumor suppressor function of RET, mutant RET has also been found in primary colorectal cancer. We now show that these mutations inactivate RET, which is consistent with RET being a tumor suppressor gene in the colon. These findings suggest that the aberrant methylation of RET and the mutational inactivation of RET promote colorectal cancer formation and that RET can serve as a tumor suppressor gene in the colon. Moreover, the increased frequency of methylated RET in colon cancers compared to adenomas suggests RET inactivation is involved in the progression of colon adenomas to cancer. PMID:22751117

Normalization of aberrant resting state functional connectivity in fibromyalgia patients following a three month physical exercise therapy.

PubMed

Flodin, P; Martinsen, S; Mannerkorpi, K; Löfgren, M; Bileviciute-Ljungar, I; Kosek, E; Fransson, P

2015-01-01

Physical exercise is one of the most efficient interventions to mitigate chronic pain symptoms in fibromyalgia (FM). However, little is known about the neurophysiological mechanisms mediating these effects. In this study we investigated resting-state connectivity using functional magnetic resonance imaging (fMRI) before and after a 15 week standardized exercise program supervised by physical therapists. Our aim was to gain an understanding of how physical exercise influences previously shown aberrant patterns of intrinsic brain activity in FM. Fourteen FM patients and eleven healthy controls successfully completed the physical exercise treatment. We investigated post- versus pre-treatment changes of brain connectivity, as well as changes in clinical symptoms in the patient group. FM patients reported improvements in symptom severity. Although several brain regions showed a treatment-related change in connectivity, only the connectivity between the right anterior insula and the left primary sensorimotor area was significantly more affected by the physical exercise among the fibromyalgia patients compared to healthy controls. Our results suggest that previously observed aberrant intrinsic brain connectivity patterns in FM are partly normalized by the physical exercise therapy. However, none of the observed normalizations in intrinsic brain connectivity were significantly correlated with symptom changes. Further studies conducted in larger cohorts are warranted to investigate the precise relationship between improvements in fibromyalgia symptoms and changes in intrinsic brain activity.

Genomic aberrations in spitzoid tumours and their implications for diagnosis, prognosis and therapy

PubMed Central

Wiesner, Thomas; Kutzner, Heinz; Cerroni, Lorenzo; Mihm, Martin J.; Busam, Klaus J.; Murali, Rajmohan

2016-01-01

Summary Histopathological evaluation of melanocytic tumours usually allows reliable distinction of benign melanocytic naevi from melanoma. More difficult is the histopathological classification of Spitz tumours, a heterogeneous group of tumours composed of large epithelioid or spindle-shaped melanocytes. Spitz tumours are biologically distinct from conventional melanocytic naevi and melanoma, as exemplified by their distinct patterns of genetic aberrations. Whereas conventional naevi and melanoma often harbour BRAF mutations, NRAS mutations, or inactivation of NF1, Spitz tumours show HRAS mutations, inactivation of BAP1 (often combined with BRAF mutations), or genomic rearrangements involving the kinases ALK, ROS1, NTRK1, BRAF, RET, and MET. In Spitz naevi, which lack significant histological atypia, all of these mitogenic driver aberrations trigger rapid cell proliferation, but after an initial growth phase, various tumour suppressive mechanisms stably block further growth. In some tumours, additional genomic aberrations may abrogate various tumour suppressive mechanisms, such as cell-cycle arrest, telomere shortening, or DNA damage response. The melanocytes then start to grow in a less organised fashion, may spread to regional lymph nodes, and are termed atypical Spitz tumours. Upon acquisition of even more aberrations, which often activate additional oncogenic pathways or reduce and alter cell differentiation, the neoplastic cells become entirely malignant and may colonise and take over distant organs (spitzoid melanoma). The sequential acquisition of genomic aberrations suggests that Spitz tumours represent a continuous biological spectrum, rather than a dichotomy of benign versus malignant, and that tumours with ambiguous histological features (atypical Spitz tumours) might be best classified as low-grade melanocytic tumours. The number of genetic aberrations usually correlates with the degree of histological atypia and explains why existing ancillary genetic techniques, such as array comparative genomic hybridisation (CGH) or fluorescence in situ hybridisation (FISH), are capable of accurately classifying histologically benign and malignant Spitz tumours, but are not very helpful in the diagnosis of ambiguous melanocytic lesions. Nevertheless, we expect that progress in our understanding of tumour genomics and progression will refine the classification of melanocytic tumours in the near future. By integrating clinical, pathological, and genetic criteria, distinct tumour subsets will be defined within the heterogeneous group of Spitz tumours, which will eventually lead to improvements in diagnosis, prognosis and therapy. PMID:27020384

Fast Neuronal Imaging using Objective Coupled Planar Illumination Microscopy

NASA Astrophysics Data System (ADS)

Tarantino, Walter

Complex computations performed by the brain are produced by activities of neuronal populations. There is a large diversity in the functions of each individual neuron, and neuronal activities occur in the time scale of milliseconds. In order to gain a fundamental understanding of the neuronal populations, one has to measure activity of each neuron at high temporal resolution, while investigating enough neurons to encapsulate the neuronal diversity. Traditional neurotechniques such as electrophysiology and optical imaging are constrained by the number of neurons whose activities can be simultaneously measured or the speed of measuring such activities. We have developed a novel light-sheet based technique called Objective Coupled Planar Illumination (OCPI) microscopy which is capable of measuring simultaneous activities of thousands of neurons at high speeds. In this thesis I pursue the following two aims: · Improve OCPI microscopy by enhancing the spatial resolution deeper in tissue. Tissue inhomogeneity and refractive index mismatch at the surface of the tissue lead to optical aberrations. We have compensated for such aberrations by (1) miniaturizing the OCPI illumination optics, so as to enable more vertical imaging of the tissue, (2) correcting for the angular defocus caused by the refraction at the immersion fluid/tissue interface, and (3) applying adaptive optics to correct for higher order optical aberrations. The improvement in the depth at which one can image tissue will enable the measurement of activities of neuronal populations in cortical areas. · Measure the diversity in the expression pattern of VSNs responsive to sulfated steroids. Nodari et al. have identified sulfated steroids as a novel family of ligands which activate vomeronasal sensory neurons (VSNs). Due to the experimental constraints, it has not been possible to obtain a comprehensive understanding of the number, location and functional characteristics of the sulfated steroid responsive VSNs. Applying OCPI microscopy and calcium imaging to simultaneously image thousands of VSNs, we show that the sulfated steroid responsive neurons (1) have unique ligand preferences, (2) are predominantly present in the apical regions of the VNO, and (3) that the choice of expression of a receptor type is not purely stochastic.

Spatially resolved wavefront aberrations of ophthalmic progressive-power lenses in normal viewing conditions.

PubMed

Villegas, Eloy A; Artal, Pablo

2003-02-01

To measure the wavefront aberration at different locations in progressive-power lenses (PPL's) isolated and in situ (PPL's plus eye). A Hartmann-Shack wavefront sensor was used to measure progressive-power lenses and human eyes either independently or in combination. In each selected zone, the lens was placed and tilted accordingly to simulate natural viewing conditions. We measured 21 relevant locations across an isolated PPL (plano lens of power addition of 2 D). In six of the locations, the wavefront aberration of the eye plus PPL were obtained in two ways: (1) by direct measurement of the system and (2) by adding the individual wavefront aberrations of the eye and the lens for each appropriate zone. In every case, we obtained the wavefront aberration as Zernike polynomials expansions, the root mean square error, the point-spread function, and the Strehl ratio. Along the corridor of the PPL, third-order coma and trefoil, and astigmatism were the dominant aberrations. In areas of the PPL outside the corridor, astigmatism increased, whereas other aberrations remained similar to the lens center. Small differences were found between the direct and calculated methods used to obtain the wavefront aberration of the eye with the lens, and the possible sources of errors were discussed. In some lenses zones, the aberrations of the lens may be compensated by the particular aberrations of the eye, yielding improved optical performance over that present in the lens alone. We designed and built a wavefront sensor to perform spatially resolved aberration measurements in ophthalmic lenses, in particular in PPL's, either isolated or in combination with the eye. The aberrations appearing in the PPL were compared with those in normal aged eyes.

Analysis of age-dependence of the anterior and posterior cornea with scheimpflug imaging.

PubMed

Nemeth, Gabor; Hassan, Ziad; Szalai, Eszter; Berta, Andras; Modis, Laszlo

2013-05-01

To assess keratometric and higher-order aberrations of the anterior and posterior cornea and their age-related changes. This study investigated one healthy eye of 227 patients (mean age: 55.15 ± 21.2 years; range: 16 to 90 years; 135 right eyes, 92 left eyes). Images were captured from each eye with Pentacam HR (Oculus Optikgeräte GmbH, Wetzlar, Germany) using automatic mode. Keratometric, astigmatism data, and corneal higher-order aberrations were analyzed. With respect to laterality, no deviance was found in any of the parameters (P > .05). Mean refractive error was 0.52 ± 0.23 diopters. The level of astigmatism decreased significantly with advancing age for both the anterior and posterior corneal surfaces (P < .05). The overall root mean square of the higher-order aberration increased continuously with age (r = 0.517; P < .01), which can be explained by the combined effect of the increased in both the anterior and posterior corneal root mean square higher-order aberrations. Of the higher-order aberrations, the constant increase of the primary and secondary spherical aberration with aging (P < .01) is caused by the spherical aberration growth of the anterior surface. Apart from these, only the vertical coma aberration of the posterior surface and the vertical trefoil aberrations of both the anterior and posterior surfaces showed a significantly positive correlation with aging (P < .05). Corneal astigmatism showed a significant decrease with aging. Of the higher-order aberrations, primary and secondary spherical aberrations, vertical coma, and vertical trefoil significantly increase with age, whereas other higher-order aberrations show no correlation with aging. Copyright 2013, SLACK Incorporated.

Redox regulation in cancer stem cells

USDA-ARS?s Scientific Manuscript database

Reactive oxygen species (ROS) and ROS-dependent (redox regulation) signaling pathways and transcriptional activities are thought to be critical in stem cell self-renewal and differentiation during growth and organogenesis. Aberrant ROS burst and dysregulation of those ROS-dependent cellular processe...

Stability Switches, Hopf Bifurcations, and Spatio-temporal Patterns in a Delayed Neural Model with Bidirectional Coupling

NASA Astrophysics Data System (ADS)

Song, Yongli; Zhang, Tonghua; Tadé, Moses O.

2009-12-01

The dynamical behavior of a delayed neural network with bi-directional coupling is investigated by taking the delay as the bifurcating parameter. Some parameter regions are given for conditional/absolute stability and Hopf bifurcations by using the theory of functional differential equations. As the propagation time delay in the coupling varies, stability switches for the trivial solution are found. Conditions ensuring the stability and direction of the Hopf bifurcation are determined by applying the normal form theory and the center manifold theorem. We also discuss the spatio-temporal patterns of bifurcating periodic oscillations by using the symmetric bifurcation theory of delay differential equations combined with representation theory of Lie groups. In particular, we obtain that the spatio-temporal patterns of bifurcating periodic oscillations will alternate according to the change of the propagation time delay in the coupling, i.e., different ranges of delays correspond to different patterns of neural activities. Numerical simulations are given to illustrate the obtained results and show the existence of bursts in some interval of the time for large enough delay.

Simultaneous acquisition of EEG and NIRS during cognitive tasks for an open access dataset.

PubMed

Shin, Jaeyoung; von Lühmann, Alexander; Kim, Do-Won; Mehnert, Jan; Hwang, Han-Jeong; Müller, Klaus-Robert

2018-02-13

We provide an open access multimodal brain-imaging dataset of simultaneous electroencephalography (EEG) and near-infrared spectroscopy (NIRS) recordings. Twenty-six healthy participants performed three cognitive tasks: 1) n-back (0-, 2- and 3-back), 2) discrimination/selection response task (DSR) and 3) word generation (WG) tasks. The data provided includes: 1) measured data, 2) demographic data, and 3) basic analysis results. For n-back (dataset A) and DSR tasks (dataset B), event-related potential (ERP) analysis was performed, and spatiotemporal characteristics and classification results for 'target' versus 'non-target' (dataset A) and symbol 'O' versus symbol 'X' (dataset B) are provided. Time-frequency analysis was performed to show the EEG spectral power to differentiate the task-relevant activations. Spatiotemporal characteristics of hemodynamic responses are also shown. For the WG task (dataset C), the EEG spectral power and spatiotemporal characteristics of hemodynamic responses are analyzed, and the potential merit of hybrid EEG-NIRS BCIs was validated with respect to classification accuracy. We expect that the dataset provided will facilitate performance evaluation and comparison of many neuroimaging analysis techniques.

Simultaneous acquisition of EEG and NIRS during cognitive tasks for an open access dataset

PubMed Central

Shin, Jaeyoung; von Lühmann, Alexander; Kim, Do-Won; Mehnert, Jan; Hwang, Han-Jeong; Müller, Klaus-Robert

2018-01-01

We provide an open access multimodal brain-imaging dataset of simultaneous electroencephalography (EEG) and near-infrared spectroscopy (NIRS) recordings. Twenty-six healthy participants performed three cognitive tasks: 1) n-back (0-, 2- and 3-back), 2) discrimination/selection response task (DSR) and 3) word generation (WG) tasks. The data provided includes: 1) measured data, 2) demographic data, and 3) basic analysis results. For n-back (dataset A) and DSR tasks (dataset B), event-related potential (ERP) analysis was performed, and spatiotemporal characteristics and classification results for ‘target’ versus ‘non-target’ (dataset A) and symbol ‘O’ versus symbol ‘X’ (dataset B) are provided. Time-frequency analysis was performed to show the EEG spectral power to differentiate the task-relevant activations. Spatiotemporal characteristics of hemodynamic responses are also shown. For the WG task (dataset C), the EEG spectral power and spatiotemporal characteristics of hemodynamic responses are analyzed, and the potential merit of hybrid EEG-NIRS BCIs was validated with respect to classification accuracy. We expect that the dataset provided will facilitate performance evaluation and comparison of many neuroimaging analysis techniques. PMID:29437166

Adaptive Local Spatiotemporal Features from RGB-D Data for One-Shot Learning Gesture Recognition

PubMed Central

Lin, Jia; Ruan, Xiaogang; Yu, Naigong; Yang, Yee-Hong

2016-01-01

Noise and constant empirical motion constraints affect the extraction of distinctive spatiotemporal features from one or a few samples per gesture class. To tackle these problems, an adaptive local spatiotemporal feature (ALSTF) using fused RGB-D data is proposed. First, motion regions of interest (MRoIs) are adaptively extracted using grayscale and depth velocity variance information to greatly reduce the impact of noise. Then, corners are used as keypoints if their depth, and velocities of grayscale and of depth meet several adaptive local constraints in each MRoI. With further filtering of noise, an accurate and sufficient number of keypoints is obtained within the desired moving body parts (MBPs). Finally, four kinds of multiple descriptors are calculated and combined in extended gradient and motion spaces to represent the appearance and motion features of gestures. The experimental results on the ChaLearn gesture, CAD-60 and MSRDailyActivity3D datasets demonstrate that the proposed feature achieves higher performance compared with published state-of-the-art approaches under the one-shot learning setting and comparable accuracy under the leave-one-out cross validation. PMID:27999337

Epigenomic Landscape of Human Fetal Brain, Heart, and Liver.

PubMed

Yan, Liying; Guo, Hongshan; Hu, Boqiang; Li, Rong; Yong, Jun; Zhao, Yangyu; Zhi, Xu; Fan, Xiaoying; Guo, Fan; Wang, Xiaoye; Wang, Wei; Wei, Yuan; Wang, Yan; Wen, Lu; Qiao, Jie; Tang, Fuchou

2016-02-26

The epigenetic regulation of spatiotemporal gene expression is crucial for human development. Here, we present whole-genome chromatin immunoprecipitation followed by high throughput DNA sequencing (ChIP-seq) analyses of a wide variety of histone markers in the brain, heart, and liver of early human embryos shortly after their formation. We identified 40,181 active enhancers, with a large portion showing tissue-specific and developmental stage-specific patterns, pointing to their roles in controlling the ordered spatiotemporal expression of the developmental genes in early human embryos. Moreover, using sequential ChIP-seq, we showed that all three organs have hundreds to thousands of bivalent domains that are marked by both H3K4me3 and H3K27me3, probably to keep the progenitor cells in these organs ready for immediate differentiation into diverse cell types during subsequent developmental processes. Our work illustrates the potentially critical roles of tissue-specific and developmental stage-specific epigenomes in regulating the spatiotemporal expression of developmental genes during early human embryonic development. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Adaptive Local Spatiotemporal Features from RGB-D Data for One-Shot Learning Gesture Recognition.

PubMed

Lin, Jia; Ruan, Xiaogang; Yu, Naigong; Yang, Yee-Hong

2016-12-17

Noise and constant empirical motion constraints affect the extraction of distinctive spatiotemporal features from one or a few samples per gesture class. To tackle these problems, an adaptive local spatiotemporal feature (ALSTF) using fused RGB-D data is proposed. First, motion regions of interest (MRoIs) are adaptively extracted using grayscale and depth velocity variance information to greatly reduce the impact of noise. Then, corners are used as keypoints if their depth, and velocities of grayscale and of depth meet several adaptive local constraints in each MRoI. With further filtering of noise, an accurate and sufficient number of keypoints is obtained within the desired moving body parts (MBPs). Finally, four kinds of multiple descriptors are calculated and combined in extended gradient and motion spaces to represent the appearance and motion features of gestures. The experimental results on the ChaLearn gesture, CAD-60 and MSRDailyActivity3D datasets demonstrate that the proposed feature achieves higher performance compared with published state-of-the-art approaches under the one-shot learning setting and comparable accuracy under the leave-one-out cross validation.

Aberrant and multiaberrant (rogue) cells in peripheral lymphocytes of Hodgkin's lymphoma patients after chemotherapy.

PubMed

Ryabchenko, Nikolay I; Nasonova, Valentina A; Fesenko, Eleonora V; Kondrashova, Tatiana V; Antoschina, Margarita M; Pavlov, Vyacheslav V; Ryabikina, Natalya V

2006-10-10

We analyzed spontaneous chromosome lesions in peripheral lymphocytes cultured from Hodgkin's lymphoma (HL) patients before and after cytostatic chemotherapy. The mean aberration frequency was significantly higher in HL patients after chemotherapy (7.20+/-0.58 per 100 metaphases) than in non-treated HL patients (4.80+/-0.54), and in non-treated patients than in healthy subjects (2.12+/-0.13). In lymphocytes of HL patients, who received chemotherapy, we found, in addition to ordinary aberrant cells, a large number of multiaberrant (or rogue) cells, i.e. metaphases carrying multiple (at least four) chromosome-type exchange aberrations. Rogue cells were found in 15 out of 18 chemotherapeutically treated HL patients (in total, 60 rogue cells per 5,568 scored cells), whereas in 30 non-treated patients only 1 rogue cell was found (per 4,988 scored cells). No correlation was found between the yield of rogue cells and the aberration frequency in ordinary aberrant cells. Aberration spectra (ratios of chromatid- to chromosome-type aberrations and of breaks to exchanges) were essentially different in ordinary aberrant and multiaberrant cells. These data, as well as analysis of cellular distributions of aberrations, implied independent induction of chromosome damage in ordinary aberrant and rogue cells. Analysis of aberration patterns in diploid and polyploid rogue metaphases belonging to the first, second, and third in vitro division indicated that rogue cells could be formed both in vivo and in vitro, and could survive at least two rounds of in vitro replication, given blocked chromosome segregation. These results suggested that formation of rogue cells, unlike ordinary aberrant cells, was triggered by events other than direct DNA and/or chromosome lesions. A hypothesis regarding disrupted apoptosis as a candidate mechanism for rogue cell formation seems to be most suitable for interpretation of our data. Cultured lymphocytes of chemotherapeutically treated HL patients may represent a model system for further examination of the multiaberrancy phenomenon.

Enhanced visual acuity and image perception following correction of highly aberrated eyes using an adaptive optics visual simulator.

PubMed

Rocha, Karolinne Maia; Vabre, Laurent; Chateau, Nicolas; Krueger, Ronald R

2010-01-01

To evaluate the changes in visual acuity and visual perception generated by correcting higher order aberrations in highly aberrated eyes using a large-stroke adaptive optics visual simulator. A crx1 Adaptive Optics Visual Simulator (Imagine Eyes) was used to correct and modify the wavefront aberrations in 12 keratoconic eyes and 8 symptomatic postoperative refractive surgery (LASIK) eyes. After measuring ocular aberrations, the device was programmed to compensate for the eye's wavefront error from the second order to the fifth order (6-mm pupil). Visual acuity was assessed through the adaptive optics system using computer-generated ETDRS opto-types and the Freiburg Visual Acuity and Contrast Test. Mean higher order aberration root-mean-square (RMS) errors in the keratoconus and symptomatic LASIK eyes were 1.88+/-0.99 microm and 1.62+/-0.79 microm (6-mm pupil), respectively. The visual simulator correction of the higher order aberrations present in the keratoconus eyes improved their visual acuity by a mean of 2 lines when compared to their best spherocylinder correction (mean decimal visual acuity with spherocylindrical correction was 0.31+/-0.18 and improved to 0.44+/-0.23 with higher order aberration correction). In the symptomatic LASIK eyes, the mean decimal visual acuity with spherocylindrical correction improved from 0.54+/-0.16 to 0.71+/-0.13 with higher order aberration correction. The visual perception of ETDRS letters was improved when correcting higher order aberrations. The adaptive optics visual simulator can effectively measure and compensate for higher order aberrations (second to fifth order), which are associated with diminished visual acuity and perception in highly aberrated eyes. The adaptive optics technology may be of clinical benefit when counseling patients with highly aberrated eyes regarding their maximum subjective potential for vision correction. Copyright 2010, SLACK Incorporated.

The mechanism by which a propeptide-encoded pH sensor regulates spatiotemporal activation of furin.

PubMed

Williamson, Danielle M; Elferich, Johannes; Ramakrishnan, Parvathy; Thomas, Gary; Shinde, Ujwal

2013-06-28

The proprotein convertase furin requires the pH gradient of the secretory pathway to regulate its multistep, compartment-specific autocatalytic activation. Although His-69 within the furin prodomain serves as the pH sensor that detects transport of the propeptide-enzyme complex to the trans-Golgi network, where it promotes cleavage and release of the inhibitory propeptide, a mechanistic understanding of how His-69 protonation mediates furin activation remains unclear. Here we employ biophysical, biochemical, and computational approaches to elucidate the mechanism underlying the pH-dependent activation of furin. Structural analyses and binding experiments comparing the wild-type furin propeptide with a nonprotonatable His-69 → Leu mutant that blocks furin activation in vivo revealed protonation of His-69 reduces both the thermodynamic stability of the propeptide as well as its affinity for furin at pH 6.0. Structural modeling combined with mathematical modeling and molecular dynamic simulations suggested that His-69 does not directly contribute to the propeptide-enzyme interface but, rather, triggers movement of a loop region in the propeptide that modulates access to the cleavage site and, thus, allows for the tight pH regulation of furin activation. Our work establishes a mechanism by which His-69 functions as a pH sensor that regulates compartment-specific furin activation and provides insights into how other convertases and proteases may regulate their precise spatiotemporal activation.

The Mechanism by Which a Propeptide-encoded pH Sensor Regulates Spatiotemporal Activation of Furin*

PubMed Central

Williamson, Danielle M.; Elferich, Johannes; Ramakrishnan, Parvathy; Thomas, Gary; Shinde, Ujwal

2013-01-01

The proprotein convertase furin requires the pH gradient of the secretory pathway to regulate its multistep, compartment-specific autocatalytic activation. Although His-69 within the furin prodomain serves as the pH sensor that detects transport of the propeptide-enzyme complex to the trans-Golgi network, where it promotes cleavage and release of the inhibitory propeptide, a mechanistic understanding of how His-69 protonation mediates furin activation remains unclear. Here we employ biophysical, biochemical, and computational approaches to elucidate the mechanism underlying the pH-dependent activation of furin. Structural analyses and binding experiments comparing the wild-type furin propeptide with a nonprotonatable His-69 → Leu mutant that blocks furin activation in vivo revealed protonation of His-69 reduces both the thermodynamic stability of the propeptide as well as its affinity for furin at pH 6.0. Structural modeling combined with mathematical modeling and molecular dynamic simulations suggested that His-69 does not directly contribute to the propeptide-enzyme interface but, rather, triggers movement of a loop region in the propeptide that modulates access to the cleavage site and, thus, allows for the tight pH regulation of furin activation. Our work establishes a mechanism by which His-69 functions as a pH sensor that regulates compartment-specific furin activation and provides insights into how other convertases and proteases may regulate their precise spatiotemporal activation. PMID:23653353

Development of five digits is controlled by a bipartite long-range cis-regulator.

PubMed

Lettice, Laura A; Williamson, Iain; Devenney, Paul S; Kilanowski, Fiona; Dorin, Julia; Hill, Robert E

2014-04-01

Conservation within intergenic DNA often highlights regulatory elements that control gene expression from a long range. How conservation within a single element relates to regulatory information and how internal composition relates to function is unknown. Here, we examine the structural features of the highly conserved ZRS (also called MFCS1) cis-regulator responsible for the spatiotemporal control of Shh in the limb bud. By systematically dissecting the ZRS, both in transgenic assays and within in the endogenous locus, we show that the ZRS is, in effect, composed of two distinct domains of activity: one domain directs spatiotemporal activity but functions predominantly from a short range, whereas a second domain is required to promote long-range activity. We show further that these two domains encode activities that are highly integrated and that the second domain is crucial in promoting the chromosomal conformational changes correlated with gene activity. During limb bud development, these activities encoded by the ZRS are interpreted differently by the fore limbs and the hind limbs; in the absence of the second domain there is no Shh activity in the fore limb, and in the hind limb low levels of Shh lead to a variant digit pattern ranging from two to four digits. Hence, in the embryo, the second domain stabilises the developmental programme providing a buffer for SHH morphogen activity and this ensures that five digits form in both sets of limbs.

Non-contact time-domain imaging of functional brain activation and heterogeneity of superficial signals

NASA Astrophysics Data System (ADS)

Wabnitz, H.; Mazurenka, M.; Di Sieno, L.; Contini, D.; Dalla Mora, A.; Farina, A.; Hoshi, Y.; Kirilina, E.; Macdonald, R.; Pifferi, A.

2017-07-01

Non-contact scanning at small source-detector separation enables imaging of cerebral and extracranial signals at high spatial resolution and their separation based on early and late photons accounting for the related spatio-temporal characteristics.

Visualizing spatiotemporal pulse propagation: first-order spatiotemporal couplings in laser pulses.

PubMed

Rhodes, Michelle; Guang, Zhe; Pease, Jerrold; Trebino, Rick

2017-04-10

Even though a general theory of first-order spatiotemporal couplings exists in the literature, it is often difficult to visualize how these distortions affect laser pulses. In particular, it is difficult to show the spatiotemporal phase of pulses in a meaningful way. Here, we propose a general solution to plotting the electric fields of pulses in three-dimensional space that intuitively shows the effects of spatiotemporal phases. The temporal phase information is color-coded using spectrograms and color response functions, and the beam is propagated to show the spatial phase evolution. Using this plotting technique, we generate two- and three-dimensional images and movies that show the effects of spatiotemporal couplings.

Visualizing spatiotemporal pulse propagation: first-order spatiotemporal couplings in laser pulses

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

Rhodes, Michelle; Guang, Zhe; Pease, Jerrold

2017-04-06

Even though a general theory of first-order spatiotemporal couplings exists in the literature, it is often difficult to visualize how these distortions affect laser pulses. In particular, it is difficult to show the spatiotemporal phase of pulses in a meaningful way. We propose a general solution to plotting the electric fields of pulses in three-dimensional space that intuitively shows the effects of spatiotemporal phases. The temporal phase information is color-coded using spectrograms and color response functions, and the beam is propagated to show the spatial phase evolution. In using this plotting technique, we generate two- and three-dimensional images and moviesmore » that show the effects of spatiotemporal couplings.« less

[Monochromatic aberration in accommodation. Dynamic wavefront analysis].

PubMed

Fritzsch, M; Dawczynski, J; Jurkutat, S; Vollandt, R; Strobel, J

2011-06-01

Monochromatic aberrations may influence the visual acuity of the eye. They are not stable and can be affected by different factors. The subject of the following paper is the dynamic investigation of the changes in wavefront aberration with accommodation. Dynamic measurement of higher and lower order aberrations was performed with a WASCA Wavefront Analyzer (Carl-Zeiss-Meditec) and a specially constructed target device for aligning objects in far and near distances on 25 subjects aged from 15 to 27 years old. Wavefront aberrations showed some significant changes in accommodation. In addition to the characteristic sphere reaction accompanying miosis and changes in horizontal prism (Z(1) (1)) in the sense of a convergence movement of the eyeball also occurred. Furthermore defocus rose (Z(2) (0)) and astigmatism (Z(2) (-2)) changed. In higher-order aberrations a decrease in coma-like Zernike polynomials (Z(3) (-1), Z(3) (1)) was found. The most obvious change appeared in spherical aberration (Z(4) (0)) which increased and changed from positive to negative. In addition the secondary astigmatism (Z(4) (-2)) and quadrafoil (Z(4) (4)) rise also increased. The total root mean square (RMS), as well as the higher-order aberrations (RMS-HO) significantly increased in accommodation which is associated with a theoretical reduction of visual acuity. An analysis of the influence of pupil size on aberrations showed significant increases in defocus, spherical aberration, quadrafoil, RMS and RMS HO by increasing pupil diameter. By accommodation-associated miosis, the growing aberrations are partially compensated by focusing on near objects. Temporal analysis of the accommodation process with dynamic wavefront analysis revealed significant delays in pupil response and changing of prism in relation to the sphere reaction. In accommodation to near objects a discrete time ahead of third order aberrations in relation to the sphere response was found. Using dynamic wavefront measurement achieved a sequential analysis of aberrations during accommodation. Significant changes in the lower and higher-order aberrations could be detected. These are additionally varied by the associated pupillary response. Moreover, the synchronicity of wave front reaction in the accommodation process was proven.

A Evaluation of Optical Aberrations in Underwater Hologrammetry

NASA Astrophysics Data System (ADS)

Kilpatrick, J. M.

Available from UMI in association with The British Library. An iterative ray-trace procedure is developed in conjunction with semi-analytic expressions for spherical aberration, coma, and astigmatism in the reconstructed holographic images of underwater objects. An exact expression for the astigmatic difference is obtained, based on the geometry of the caustic for refraction. The geometrical characteristics of the aberrated images associated with axial and non-axial field positions are represented by ray intersection diagrams. A third order expression for the wavefront aberration introduced at a planar air/water boundary is given. The associated third order aberration coefficients are used to obtain analytic expressions for the aberrations observed in underwater hologrammetry. The results of the third order treatment are shown to give good agreement with the results obtained by geometrical ray tracing and by direct measurement on the reconstructed real image. The third order aberration coefficients are employed to estimate the limit of resolution in the presence of the aberrations associated with reconstruction in air. In concurrence with practical observations it is found that the estimated resolution is primarily limited by astigmatism. The limitations of the planar window in underwater imaging applications are outlined and various schemes are considered to effect a reduction in the extent of aberration. The analogous problems encountered in underwater photography are examined in order to establish the grounds for a common solution based on a conventional optical corrector. The performance of one such system, the Ivanoff Corrector, is investigated. The spherical aberration associated with axial image formation is evaluated. The equivalence of the third order wavefront aberration introduced at a planar air/water boundary to that introduced upon reconstruction by an appropriate wavelength change is shown to provide a basis for the compensation of aberrations in underwater hologrammetry. The results of experimental trials which demonstrate the correction of astigmatism and field curvature are presented. Exact expressions are obtained for the aberrations in wavelength compensated holograms and are employed to determine the conditions for optimum compensation and the degree of residual aberration. (Abstract shortened by UMI.).

System and Method for Null-Lens Wavefront Sensing

NASA Technical Reports Server (NTRS)

Hill, Peter C. (Inventor); Thompson, Patrick L. (Inventor); Aronstein, David L. (Inventor); Bolcar, Matthew R. (Inventor); Smith, Jeffrey S. (Inventor)

2015-01-01

A method of measuring aberrations in a null-lens including assembly and alignment aberrations. The null-lens may be used for measuring aberrations in an aspheric optic with the null-lens. Light propagates from the aspheric optic location through the null-lens, while sweeping a detector through the null-lens focal plane. Image data being is collected at locations about said focal plane. Light is simulated propagating to the collection locations for each collected image. Null-lens aberrations may extracted, e.g., applying image-based wavefront-sensing to collected images and simulation results. The null-lens aberrations improve accuracy in measuring aspheric optic aberrations.

[Comparative analysis of cytogenetic examination of control groups of subjects carried out in different Russian laboratories].

PubMed

Sevan'kaev, A V; Khvostunov, I K; Snigireva, G P; Novitskaia, N N; Antoshchina, M M; Fesenko, E V; Vorobtsova, I E; Neronova, E G; Domracheva, E V; Nugis, V Iu; Govorun, R D; Handogina, E K

2013-01-01

The incidence of unstable chromosome aberrations in peripheral blood lymphocytes from unirradiated control subjects was analyzed using cytogenetic data obtained from 9 cytogenetic laboratories located in Moscow, St.-Petersburg, Obninsk, and Dubna (Russia). The objective of this study was to estimate the level and spectrum of spontaneous chromosome aberrations in human lymphocytes. 1140 blood samples were taken from 1112 subjects (594 men and 546 women) aged 1 to 72. The total metaphase number was 466795. The uniform Giemsa method for peripheral blood lymphocyte cultures was used. After counting 466795 metaphases, 4288 chromosomal aberrations of various types were classified. The most frequent types of aberrations were acentrics and chromatid deletions. They made up 90% of the total number of aberrations. The remaining 10% were exchange aberrations. The number of chromosome exchanges (dicentrics and centric rings) was twice the number of chromatid exchanges. Overall, the portion ofcells with chromosomal or (and) chromatid aberrations was 0.89 +/- 0.01%; the frequency of acentrics was 0.29 +/- 0.01; the frequency of dicentrics was 0.046 +/- 0.003; the frequency of unstable chromosome aberrations was 0.35 +/- 0.01; and the frequency of chromatid aberrations was 0.57 +/- 0.01 per 100 cells.

Structural centrosome aberrations promote non-cell-autonomous invasiveness.

PubMed

Ganier, Olivier; Schnerch, Dominik; Oertle, Philipp; Lim, Roderick Yh; Plodinec, Marija; Nigg, Erich A

2018-05-02

Centrosomes are the main microtubule-organizing centers of animal cells. Although centrosome aberrations are common in tumors, their consequences remain subject to debate. Here, we studied the impact of structural centrosome aberrations, induced by deregulated expression of ninein-like protein (NLP), on epithelial spheres grown in Matrigel matrices. We demonstrate that NLP-induced structural centrosome aberrations trigger the escape ("budding") of living cells from epithelia. Remarkably, all cells disseminating into the matrix were undergoing mitosis. This invasive behavior reflects a novel mechanism that depends on the acquisition of two distinct properties. First, NLP-induced centrosome aberrations trigger a re-organization of the cytoskeleton, which stabilizes microtubules and weakens E-cadherin junctions during mitosis. Second, atomic force microscopy reveals that cells harboring these centrosome aberrations display increased stiffness. As a consequence, mitotic cells are pushed out of mosaic epithelia, particularly if they lack centrosome aberrations. We conclude that centrosome aberrations can trigger cell dissemination through a novel, non-cell-autonomous mechanism, raising the prospect that centrosome aberrations contribute to the dissemination of metastatic cells harboring normal centrosomes. © 2018 The Authors. Published under the terms of the CC BY NC ND 4.0 license.

A model of distributed phase aberration for deblurring phase estimated from scattering.

PubMed

Tillett, Jason C; Astheimer, Jeffrey P; Waag, Robert C

2010-01-01

Correction of aberration in ultrasound imaging uses the response of a point reflector or its equivalent to characterize the aberration. Because a point reflector is usually unavailable, its equivalent is obtained using statistical methods, such as processing reflections from multiple focal regions in a random medium. However, the validity of methods that use reflections from multiple points is limited to isoplanatic patches for which the aberration is essentially the same. In this study, aberration is modeled by an offset phase screen to relax the isoplanatic restriction. Methods are developed to determine the depth and phase of the screen and to use the model for compensation of aberration as the beam is steered. Use of the model to enhance the performance of the noted statistical estimation procedure is also described. Experimental results obtained with tissue-mimicking phantoms that implement different models and produce different amounts of aberration are presented to show the efficacy of these methods. The improvement in b-scan resolution realized with the model is illustrated. The results show that the isoplanatic patch assumption for estimation of aberration can be relaxed and that propagation-path characteristics and aberration estimation are closely related.

Region-specific network plasticity in simulated and living cortical networks: comparison of the center of activity trajectory (CAT) with other statistics

NASA Astrophysics Data System (ADS)

Chao, Zenas C.; Bakkum, Douglas J.; Potter, Steve M.

2007-09-01

Electrically interfaced cortical networks cultured in vitro can be used as a model for studying the network mechanisms of learning and memory. Lasting changes in functional connectivity have been difficult to detect with extracellular multi-electrode arrays using standard firing rate statistics. We used both simulated and living networks to compare the ability of various statistics to quantify functional plasticity at the network level. Using a simulated integrate-and-fire neural network, we compared five established statistical methods to one of our own design, called center of activity trajectory (CAT). CAT, which depicts dynamics of the location-weighted average of spatiotemporal patterns of action potentials across the physical space of the neuronal circuitry, was the most sensitive statistic for detecting tetanus-induced plasticity in both simulated and living networks. By reducing the dimensionality of multi-unit data while still including spatial information, CAT allows efficient real-time computation of spatiotemporal activity patterns. Thus, CAT will be useful for studies in vivo or in vitro in which the locations of recording sites on multi-electrode probes are important.

A Coincidence Detection Mechanism Controls PX-BAR Domain-Mediated Endocytic Membrane Remodeling via an Allosteric Structural Switch.

PubMed

Lo, Wen-Ting; Vujičić Žagar, Andreja; Gerth, Fabian; Lehmann, Martin; Puchkov, Dymtro; Krylova, Oxana; Freund, Christian; Scapozza, Leonardo; Vadas, Oscar; Haucke, Volker

2017-11-20

Clathrin-mediated endocytosis occurs by bending and remodeling of the membrane underneath the coat. Bin-amphiphysin-rvs (BAR) domain proteins are crucial for endocytic membrane remodeling, but how their activity is spatiotemporally controlled is largely unknown. We demonstrate that the membrane remodeling activity of sorting nexin 9 (SNX9), a late-acting endocytic PX-BAR domain protein required for constriction of U-shaped endocytic intermediates, is controlled by an allosteric structural switch involving coincident detection of the clathrin adaptor AP2 and phosphatidylinositol-3,4-bisphosphate (PI(3,4)P 2 ) at endocytic sites. Structural, biochemical, and cell biological data show that SNX9 is autoinhibited in solution. Binding to PI(3,4)P 2 via its PX-BAR domain, and concomitant association with AP2 via sequences in the linker region, releases SNX9 autoinhibitory contacts to enable membrane constriction. Our results reveal a mechanism for restricting the latent membrane remodeling activity of BAR domain proteins to allow spatiotemporal coupling of membrane constriction to the progression of the endocytic pathway. Copyright © 2017 Elsevier Inc. All rights reserved.

Protein Tyrosine Phosphatase-PEST and β8 Integrin Regulate Spatiotemporal Patterns of RhoGDI1 Activation in Migrating Cells

PubMed Central

Lee, Hye Shin; Cheerathodi, Mujeeburahiman; Chaki, Sankar P.; Reyes, Steve B.; Zheng, Yanhua; Lu, Zhimin; Paidassi, Helena; DerMardirossian, Celine; Lacy-Hulbert, Adam; Rivera, Gonzalo M.

2015-01-01

Directional cell motility is essential for normal development and physiology, although how motile cells spatiotemporally activate signaling events remains largely unknown. Here, we have characterized an adhesion and signaling unit comprised of protein tyrosine phosphatase (PTP)-PEST and the extracellular matrix (ECM) adhesion receptor β8 integrin that plays essential roles in directional cell motility. β8 integrin and PTP-PEST form protein complexes at the leading edge of migrating cells and balance patterns of Rac1 and Cdc42 signaling by controlling the subcellular localization and phosphorylation status of Rho GDP dissociation inhibitor 1 (RhoGDI1). Translocation of Src-phosphorylated RhoGDI1 to the cell's leading edge promotes local activation of Rac1 and Cdc42, whereas dephosphorylation of RhoGDI1 by integrin-bound PTP-PEST promotes RhoGDI1 release from the membrane and sequestration of inactive Rac1/Cdc42 in the cytoplasm. Collectively, these data reveal a finely tuned regulatory mechanism for controlling signaling events at the leading edge of directionally migrating cells. PMID:25666508

Comparison of spatiotemporal cortical activation pattern during visual perception of Korean, English, Chinese words: an event-related potential study.

PubMed

Kim, Kyung Hwan; Kim, Ja Hyun

2006-02-20

The aim of this study was to compare spatiotemporal cortical activation patterns during the visual perception of Korean, English, and Chinese words. The comparison of these three languages offers an opportunity to study the effect of written forms on cortical processing of visually presented words, because of partial similarity/difference among words of these languages, and the familiarity of native Koreans with these three languages at the word level. Single-character words and pictograms were excluded from the stimuli in order to activate neuronal circuitries that are involved only in word perception. Since a variety of cerebral processes are sequentially evoked during visual word perception, a high-temporal resolution is required and thus we utilized event-related potential (ERP) obtained from high-density electroencephalograms. The differences and similarities observed from statistical analyses of ERP amplitudes, the correlation between ERP amplitudes and response times, and the patterns of current source density, appear to be in line with demands of visual and semantic analysis resulting from the characteristics of each language, and the expected task difficulties for native Korean subjects.

Encoding of Spatio-Temporal Input Characteristics by a CA1 Pyramidal Neuron Model

PubMed Central

Pissadaki, Eleftheria Kyriaki; Sidiropoulou, Kyriaki; Reczko, Martin; Poirazi, Panayiota

2010-01-01

The in vivo activity of CA1 pyramidal neurons alternates between regular spiking and bursting, but how these changes affect information processing remains unclear. Using a detailed CA1 pyramidal neuron model, we investigate how timing and spatial arrangement variations in synaptic inputs to the distal and proximal dendritic layers influence the information content of model responses. We find that the temporal delay between activation of the two layers acts as a switch between excitability modes: short delays induce bursting while long delays decrease firing. For long delays, the average firing frequency of the model response discriminates spatially clustered from diffused inputs to the distal dendritic tree. For short delays, the onset latency and inter-spike-interval succession of model responses can accurately classify input signals as temporally close or distant and spatially clustered or diffused across different stimulation protocols. These findings suggest that a CA1 pyramidal neuron may be capable of encoding and transmitting presynaptic spatiotemporal information about the activity of the entorhinal cortex-hippocampal network to higher brain regions via the selective use of either a temporal or a rate code. PMID:21187899

Cdc42 and formin activity control non-muscle myosin dynamics during Drosophila heart morphogenesis

PubMed Central

Vogler, Georg; Liu, Jiandong; Iafe, Timothy W.; Migh, Ede; Mihály, József

2014-01-01

During heart formation, a network of transcription factors and signaling pathways guide cardiac cell fate and differentiation, but the genetic mechanisms orchestrating heart assembly and lumen formation remain unclear. Here, we show that the small GTPase Cdc42 is essential for Drosophila melanogaster heart morphogenesis and lumen formation. Cdc42 genetically interacts with the cardiogenic transcription factor tinman; with dDAAM which belongs to the family of actin organizing formins; and with zipper, which encodes nonmuscle myosin II. Zipper is required for heart lumen formation, and its spatiotemporal activity at the prospective luminal surface is controlled by Cdc42. Heart-specific expression of activated Cdc42, or the regulatory formins dDAAM and Diaphanous caused mislocalization of Zipper and induced ectopic heart lumina, as characterized by luminal markers such as the extracellular matrix protein Slit. Placement of Slit at the lumen surface depends on Cdc42 and formin function. Thus, Cdc42 and formins play pivotal roles in heart lumen formation through the spatiotemporal regulation of the actomyosin network. PMID:25267295

Neural Sequence Generation Using Spatiotemporal Patterns of Inhibition.

PubMed

Cannon, Jonathan; Kopell, Nancy; Gardner, Timothy; Markowitz, Jeffrey

2015-11-01

Stereotyped sequences of neural activity are thought to underlie reproducible behaviors and cognitive processes ranging from memory recall to arm movement. One of the most prominent theoretical models of neural sequence generation is the synfire chain, in which pulses of synchronized spiking activity propagate robustly along a chain of cells connected by highly redundant feedforward excitation. But recent experimental observations in the avian song production pathway during song generation have shown excitatory activity interacting strongly with the firing patterns of inhibitory neurons, suggesting a process of sequence generation more complex than feedforward excitation. Here we propose a model of sequence generation inspired by these observations in which a pulse travels along a spatially recurrent excitatory chain, passing repeatedly through zones of local feedback inhibition. In this model, synchrony and robust timing are maintained not through redundant excitatory connections, but rather through the interaction between the pulse and the spatiotemporal pattern of inhibition that it creates as it circulates the network. These results suggest that spatially and temporally structured inhibition may play a key role in sequence generation.

Aberration Compensation in Aplanatic Solid Immersion Lens Microscopy

DTIC Science & Technology

2013-11-08

model and ray tracing software ( Zemax ) to understand how much aberrations are in the system and how much can be compensated by the DM. Subsequently...aberration. Table 2 shows the Zemax simulation on this particular case. With aberration compensation, the finest resolvable group is at 252 nm

Measurement of inter- and intra-annual variability of landscape fire activity at a continental scale: The Australian case

Treesearch

Grant J. Williamson; Lynda D. Prior; Matt Jolly; Mark A. Cochrane; Brett P. Murphy; David M. J. S. Bowman

2016-01-01

Climate dynamics at diurnal, seasonal and inter-annual scales shape global fire activity, although difficulties of assembling reliable fire and meteorological data with sufficient spatio-temporal resolution have frustrated quantification of this variability. Using Australia as a case study, we combine data from 4760 meteorological stations with 12 years of satellite-...

Physico-chemical characteristics and methanogen communities in swine and dairy manure storage tanks: spatio-temporal variations and impact on methanogenic activity.

PubMed

Barret, Maialen; Gagnon, Nathalie; Topp, Edward; Masse, Lucie; Massé, Daniel I; Talbot, Guylaine

2013-02-01

Greenhouse gas emissions represent a major environmental problem associated with the management of manure from the livestock industry. Methane is the primary GHG emitted during manure outdoor storage. In this paper, the variability of two swine and two dairy manure storage tanks was surveyed, in terms of physico-chemical and microbiological parameters. The impact of the inter-tank and spatio-temporal variations of these parameters on the methanogenic activity of manure was ascertained. A Partial Least Square regression was carried out, which demonstrated that physico-chemical as well as microbiological parameters had a major influence on the methanogenic activity. Among the 19 parameters included in the regression, the concentrations of VFAs had the strongest negative influence on the methane emission rate of manure, resulting from their well-known inhibitory effect. The relative abundance of two amplicons in archaeal fingerprints was found to positively influence the methanogenic activity, suggesting that Methanoculleus spp. and possibly Methanosarcina spp. are major contributors to methanogenesis in storage tanks. This work gave insights into the mechanisms, which drive methanogenesis in swine and dairy manure storage tanks. Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.

Cortical Entropy, Mutual Information and Scale-Free Dynamics in Waking Mice.

PubMed

Fagerholm, Erik D; Scott, Gregory; Shew, Woodrow L; Song, Chenchen; Leech, Robert; Knöpfel, Thomas; Sharp, David J

2016-10-01

Some neural circuits operate with simple dynamics characterized by one or a few well-defined spatiotemporal scales (e.g. central pattern generators). In contrast, cortical neuronal networks often exhibit richer activity patterns in which all spatiotemporal scales are represented. Such "scale-free" cortical dynamics manifest as cascades of activity with cascade sizes that are distributed according to a power-law. Theory and in vitro experiments suggest that information transmission among cortical circuits is optimized by scale-free dynamics. In vivo tests of this hypothesis have been limited by experimental techniques with insufficient spatial coverage and resolution, i.e., restricted access to a wide range of scales. We overcame these limitations by using genetically encoded voltage imaging to track neural activity in layer 2/3 pyramidal cells across the cortex in mice. As mice recovered from anesthesia, we observed three changes: (a) cortical information capacity increased, (b) information transmission among cortical regions increased and (c) neural activity became scale-free. Our results demonstrate that both information capacity and information transmission are maximized in the awake state in cortical regions with scale-free network dynamics. © The Author 2016. Published by Oxford University Press.

A variational Bayes spatiotemporal model for electromagnetic brain mapping.

PubMed

Nathoo, F S; Babul, A; Moiseev, A; Virji-Babul, N; Beg, M F

2014-03-01

In this article, we present a new variational Bayes approach for solving the neuroelectromagnetic inverse problem arising in studies involving electroencephalography (EEG) and magnetoencephalography (MEG). This high-dimensional spatiotemporal estimation problem involves the recovery of time-varying neural activity at a large number of locations within the brain, from electromagnetic signals recorded at a relatively small number of external locations on or near the scalp. Framing this problem within the context of spatial variable selection for an underdetermined functional linear model, we propose a spatial mixture formulation where the profile of electrical activity within the brain is represented through location-specific spike-and-slab priors based on a spatial logistic specification. The prior specification accommodates spatial clustering in brain activation, while also allowing for the inclusion of auxiliary information derived from alternative imaging modalities, such as functional magnetic resonance imaging (fMRI). We develop a variational Bayes approach for computing estimates of neural source activity, and incorporate a nonparametric bootstrap for interval estimation. The proposed methodology is compared with several alternative approaches through simulation studies, and is applied to the analysis of a multimodal neuroimaging study examining the neural response to face perception using EEG, MEG, and fMRI. © 2013, The International Biometric Society.

Theoretical investigation of aberrations upon ametropic human eyes

NASA Astrophysics Data System (ADS)

Tan, Bo; Chen, Ying-Ling; Lewis, J. W. L.; Baker, Kevin

2003-11-01

The human eye aberrations are important for visual acuity and ophthalmic diagnostics and surgical procedures. Reported monochromatic aberration data of the normal 20/20 human eyes are scarce. There exist even fewer reports of the relation between ametropic conditions and aberrations. We theoretically investigate the monochromatic and chromatic aberrations of human eyes for refractive errors of -10 to +10 diopters. Schematic human eye models are employed using optical design software for axial, index, and refractive types of ametropia.

Frontal responses during learning predict vulnerability to the psychotogenic effects of ketamine: linking cognition, brain activity, and psychosis.

PubMed

Corlett, Philip R; Honey, Garry D; Aitken, Michael R F; Dickinson, Anthony; Shanks, David R; Absalom, Anthony R; Lee, Michael; Pomarol-Clotet, Edith; Murray, Graham K; McKenna, Peter J; Robbins, Trevor W; Bullmore, Edward T; Fletcher, Paul C

2006-06-01

Establishing a neurobiological account of delusion formation that links cognitive processes, brain activity, and symptoms is important to furthering our understanding of psychosis. To explore a theoretical model of delusion formation that implicates prediction error-dependent associative learning processes in a pharmacological functional magnetic resonance imaging study using the psychotomimetic drug ketamine. Within-subject, randomized, placebo-controlled study. Hospital-based clinical research facility, Addenbrooke's Hospital, Cambridge, England. The work was completed within the Wellcome Trust and Medical Research Council Behavioral and Clinical Neuroscience Institute, Cambridge. Fifteen healthy, right-handed volunteers (8 of whom were male) with a mean +/- SD age of 29 +/- 7 years and a mean +/- SD predicted full-scale IQ of 113 +/- 4 were recruited from within the local community by advertisement. Subjects were given low-dose ketamine (100 ng/mL of plasma) or placebo while performing a causal associative learning task during functional magnetic resonance imaging. In a separate session outside the scanner, the dose was increased (to 200 ng/mL of plasma) and subjects underwent a structured clinical interview. Brain activation, blood plasma levels of ketamine, and scores from psychiatric ratings scales (Brief Psychiatric Ratings Scale, Present State Examination, and Clinician-Administered Dissociative States Scale). Low-dose ketamine perturbs error-dependent learning activity in the right frontal cortex (P = .03). High-dose ketamine produces perceptual aberrations (P = .01) and delusion-like beliefs (P = .007). Critically, subjects showing the highest degree of frontal activation with placebo show the greatest occurrence of drug-induced perceptual aberrations (P = .03) and ideas or delusions of reference (P = .04). These findings relate aberrant prediction error-dependent associative learning to referential ideas and delusions via a perturbation of frontal cortical function. They are consistent with a model of delusion formation positing disruptions in error-dependent learning.

Essential role of carbonic anhydrase XII in secretory gland fluid and HCO3 (-) secretion revealed by disease causing human mutation.

PubMed

Hong, Jeong Hee; Muhammad, Emad; Zheng, Changyu; Hershkovitz, Eli; Alkrinawi, Soliman; Loewenthal, Neta; Parvari, Ruti; Muallem, Shmuel

2015-12-15

Fluid and HCO3 (-) secretion is essential for all epithelia; aberrant secretion is associated with several diseases. Carbonic anhydrase XII (CA12) is the key carbonic anhydrase in epithelial fluid and HCO3 (-) secretion and works by activating the ductal Cl(-) -HCO3 (-) exchanger AE2. Delivery of CA12 to salivary glands increases salivation in mice and of the human mutation CA12(E143K) markedly inhibits it. The human mutation CA12(E143K) causes disease due to aberrant CA12 glycosylation, and misfolding resulting in loss of AE2 activity. Aberrant epithelial fluid and HCO3 (-) secretion is associated with many diseases. The activity of HCO3 (-) transporters depends of HCO3 (-) availability that is determined by carbonic anhydrases (CAs). Which CAs are essential for epithelial function is unknown. CA12 stands out since the CA12(E143K) mutation causes salt wasting in sweat and dehydration in humans. Here, we report that expression of CA12 and of CA12(E143K) in mice salivary glands respectively increased and prominently inhibited ductal fluid secretion and salivation in vivo. CA12 markedly increases the activity and is the major HCO3 (-) supplier of ductal Cl(-) -HCO3 (-) exchanger AE2, but not of NBCe1-B. The E143K mutation alters CA12 glycosylation at N28 and N80, resulting in retention of the basolateral CA12 in the ER. Knockdown of AE2 and of CA12 inhibited pancreatic and salivary gland ductal AE2 activity and fluid secretion. Accordingly, patients homozygous for the CA12(E143K) mutation have a dry mouth, dry tongue phenotype. These findings reveal an unsuspected prominent role of CA12 in epithelial function, explain the disease and call for caution in the use of CA12 inhibitors in cancer treatment. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

Single and Compound Knock-outs of MicroRNA (miRNA)-155 and Its Angiogenic Gene Target CCN1 in Mice Alter Vascular and Neovascular Growth in the Retina via Resident Microglia.

PubMed

Yan, Lulu; Lee, Sangmi; Lazzaro, Douglas R; Aranda, Jacob; Grant, Maria B; Chaqour, Brahim

2015-09-18

The response of the retina to ischemic insult typically leads to aberrant retinal neovascularization, a major cause of blindness. The epigenetic regulation of angiogenic gene expression by miRNAs provides new prospects for their therapeutic utility in retinal neovascularization. Here, we focus on miR-155, a microRNA functionally important in inflammation, which is of paramount importance in the pathogenesis of retinal neovascularization. Whereas constitutive miR-155-deficiency in mice results in mild vascular defects, forced expression of miR-155 causes endothelial hyperplasia and increases microglia count and activation. The mouse model of oxygen-induced retinopathy, which recapitulates ischemia-induced aberrant neovessel growth, is characterized by increased expression of miR-155 and localized areas of microglia activation. Interestingly, miR-155 deficiency in mice reduces microglial activation, curtails abnormal vessel growth, and allows for rapid normalization of the retinal vasculature following ischemic insult. miR-155 binds to the 3'-UTR and represses the expression of the CCN1 gene, which encodes an extracellular matrix-associated integrin-binding protein that both promotes physiological angiogenesis and harnesses growth factor-induced abnormal angiogenic responses. Single CCN1 deficiency or double CCN1 and miR-155 knock-out in mice causes retinal vascular malformations typical of faulty maturation, mimicking the vascular alterations of miR-155 gain of function. During development, the miR-155/CCN1 regulatory axis balances the proangiogenic and proinflammatory activities of microglia to allow for their function as guideposts for sprout fusion and anastomosis. Under ischemic conditions, dysregulated miR-155 and CCN1 expression increases the inflammatory load and microglial activation, prompting aberrant angiogenic responses. Thus, miR-155 functions in tandem with CCN1 to modulate inflammation-induced vascular homeostasis and repair. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Single and Compound Knock-outs of MicroRNA (miRNA)-155 and Its Angiogenic Gene Target CCN1 in Mice Alter Vascular and Neovascular Growth in the Retina via Resident Microglia*

PubMed Central

Yan, Lulu; Lee, Sangmi; Lazzaro, Douglas R.; Aranda, Jacob; Grant, Maria B.; Chaqour, Brahim

2015-01-01

The response of the retina to ischemic insult typically leads to aberrant retinal neovascularization, a major cause of blindness. The epigenetic regulation of angiogenic gene expression by miRNAs provides new prospects for their therapeutic utility in retinal neovascularization. Here, we focus on miR-155, a microRNA functionally important in inflammation, which is of paramount importance in the pathogenesis of retinal neovascularization. Whereas constitutive miR-155-deficiency in mice results in mild vascular defects, forced expression of miR-155 causes endothelial hyperplasia and increases microglia count and activation. The mouse model of oxygen-induced retinopathy, which recapitulates ischemia-induced aberrant neovessel growth, is characterized by increased expression of miR-155 and localized areas of microglia activation. Interestingly, miR-155 deficiency in mice reduces microglial activation, curtails abnormal vessel growth, and allows for rapid normalization of the retinal vasculature following ischemic insult. miR-155 binds to the 3′-UTR and represses the expression of the CCN1 gene, which encodes an extracellular matrix-associated integrin-binding protein that both promotes physiological angiogenesis and harnesses growth factor-induced abnormal angiogenic responses. Single CCN1 deficiency or double CCN1 and miR-155 knock-out in mice causes retinal vascular malformations typical of faulty maturation, mimicking the vascular alterations of miR-155 gain of function. During development, the miR-155/CCN1 regulatory axis balances the proangiogenic and proinflammatory activities of microglia to allow for their function as guideposts for sprout fusion and anastomosis. Under ischemic conditions, dysregulated miR-155 and CCN1 expression increases the inflammatory load and microglial activation, prompting aberrant angiogenic responses. Thus, miR-155 functions in tandem with CCN1 to modulate inflammation-induced vascular homeostasis and repair. PMID:26242736

STAT3 Inhibitory Activity of Structurally Simplified Withaferin A Analogues.

PubMed

Tahara, Teruyuki; Streit, Ursula; Pelish, Henry E; Shair, Matthew D

2017-04-07

Signal transducer and activator of transcription 3 (STAT3) is a component of the JAK/STAT pathway. Therapeutic inhibition of STAT3 has been of high interest, as its aberrant activation has been linked to cancer, inflammation, and other human diseases. The withanolide family natural product withaferin A (1) inhibits STAT3 activation. We designed, synthesized, and evaluated simplified withanolide analogues SLW1 (3) and SLW2 (4), and found that SLW1 retained the STAT3 inhibitory activity of withaferin A.

Protease activation during in vivo pancreatitis is dependent on calcineurin activation.

PubMed

Shah, Ahsan U; Sarwar, Amna; Orabi, Abrahim I; Gautam, Samir; Grant, Wayne M; Park, Alexander J; Shah, Adnan U; Liu, Jun; Mistry, Pramod K; Jain, Dhanpat; Husain, Sohail Z

2009-11-01

The premature activation of digestive proenzymes, specifically proteases, within the pancreatic acinar cell is an early and critical event during acute pancreatitis. Our previous studies demonstrate that this activation requires a distinct pathological rise in cytosolic Ca(2+). Furthermore, we have shown that a target of aberrant Ca(2+) in acinar cells is the Ca(2+)/calmodulin-dependent phosphatase calcineurin (PP2B). In this study, we hypothesized that PP2B mediates in vivo protease activation and pancreatitis severity. To test this, pancreatitis was induced in mice over 8 h by administering hourly intraperitoneal injections of the cholecystokinin analog caerulein (50 microg/kg). Treatment with the PP2B inhibitor FK506 at 1 and 8 h after pancreatitis induction reduced trypsin activities by greater than 50% (P < 0.005). Serum amylase and IL-6 was reduced by 86 and 84% relative to baseline (P < 0.0005) at 8 h, respectively. Histological severity of pancreatitis, graded on the basis of pancreatic edema, acinar cell vacuolization, inflammation, and apoptosis, was reduced early in the course of pancreatitis. Myeloperoxidase activity from both pancreas and lung was reduced by 93 and 83% relative to baseline, respectively (P < 0.05). These data suggest that PP2B is an important target of the aberrant acinar cell Ca(2+) rise associated with pathological protease activation and pancreatitis.

Aberrant RNA splicing and mutations in spliceosome complex in acute myeloid leukemia.

PubMed

Zhou, Jianbiao; Chng, Wee-Joo

2017-01-01

The spliceosome, the cellular splicing machinery, regulates RNA splicing of messenger RNA precursors (pre-mRNAs) into maturation of protein coding RNAs. Recurrent mutations and copy number changes in genes encoding spliceosomal proteins and splicing regulatory factors have tumor promoting or suppressive functions in hematological malignancies, as well as some other cancers. Leukemia stem cell (LSC) populations, although rare, are essential contributors of treatment failure and relapse. Recent researches have provided the compelling evidence that link the erratic spicing activity to the LSC phenotype in acute myeloid leukemia (AML). In this article, we describe the diverse roles of aberrant splicing in hematological malignancies, particularly in AML and their contributions to the characteristics of LSC. We review these promising strategies to exploit the addiction of aberrant spliceosomal machinery for anti-leukemic therapy with aim to eradicate LSC. However, given the complexity and plasticity of spliceosome and not fully known functions of splicing in cancer, the challenges facing the development of the therapeutic strategies targeting RAN splicing are highlighted and future directions are discussed too.

Advanced Orion Optimized Laser System Analysis

NASA Technical Reports Server (NTRS)

1996-01-01

Contractor shall perform a complete analysis of the potential of the solid state laser in the very long pulse mode (100 ns pulse width, 10-30 hz rep-rate) and in the very short pulse mode (100 ps pulse width 10-30 hz rep rate) concentrating on the operation of the device in the 'hot-rod' mode, where no active cooling the laser operation is attempted. Contractor's calculations shall be made of the phase aberrations which develop during the repped-pulse train, and the results shall feed into the adaptive optics analyses. The contractor shall devise solutions to work around ORION track issues. A final report shall be furnished to the MSFC COTR including all calculations and analysis of estimates of bulk phase and intensity aberration distribution in the laser output beam as a function of time during the repped-pulse train for both wave forms (high-energy/long-pulse, as well as low-energy/short-pulse). Recommendations shall be made for mitigating the aberrations by laser re-design and/or changes in operating parameters of optical pump sources and/or designs.

Tuberous sclerosis: aberrant metabolism of ornithine, proline and glutamate in cultured fibroblasts.

PubMed

Tanaka, H; Nakazawa, K; Arima, M; Hayashi, A

1987-01-01

To investigate aberrant metabolism of proline (Pro) and its precursors in tuberous sclerosis (TS), 6, 7 and 5 strains of control, TS (normal skin) and TS (tumor) fibroblasts, respectively, were cultured in Eagle's MEM containing dialyzed fetal bovine serum with or without 0.1 mM ornithine (Orn). Ornithine aminotransferase (OAT) activity was decreased in TS, especially in TS (tumor) after mild sonication treatment. The yield of the OAT protein was inhibited in TS (tumor) when cultured without Orn. Free glutamate (Glu) in the medium was significantly increased in TS (tumor). Free proline (Pro) in cells was significantly decreased in TS (tumor) when cultured with Orn, but protein-bound Pro was not. The relative concentration of free Glu to glutamine (Gln) in the medium and that of free Glu to Pro in cells cultured with Orn were increased in TS (tumor). These results suggest that the requirement for Orn, increased turnover of Pro to Glu and increased elimination of Glu into the medium occur in TS (tumor). Aberrant regulation or turnover of Pro and Glu metabolism may occur in TS, especially in tumor cells.

Novel adaptive fiber-optics collimator for coherent beam combination.

PubMed

Zhi, Dong; Ma, Pengfei; Ma, Yanxing; Wang, Xiaolin; Zhou, Pu; Si, Lei

2014-12-15

In this manuscript, we experimentally validate a novel design of adaptive fiber-optics collimator (AFOC), which utilizes two levers to enlarge the movable range of the fiber end cap. The enlargement of the range makes the new AFOC possible to compensate the end-cap/tilt aberration in fiber laser beam combining system. The new AFOC based on flexible hinges and levers was fabricated and the performance of the new AFOC was tested carefully, including its control range, frequency response and control accuracy. Coherent beam combination (CBC) of two 5-W fiber amplifiers array with simultaneously end-cap/tilt control and phase-locking control was implemented successfully with the novel AFOC. Experimental results show that the average normalized power in the bucket (PIB) value increases from 0.311 to 0.934 with active phasing and tilt aberration compensation simultaneously, and with both controls on, the fringe contrast improves to more than 82% from 0% for the case with both control off. This work presents a promising structure for tilt aberration control in high power CBC system.

A multi-conjugate adaptive optics testbed using two MEMS deformable mirrors

NASA Astrophysics Data System (ADS)

Andrews, Jonathan R.; Martinez, Ty; Teare, Scott W.; Restaino, Sergio R.; Wilcox, Christopher C.; Santiago, Freddie; Payne, Don M.

2011-03-01

Adaptive optics (AO) systems are well demonstrated in the literature with both laboratory and real-world systems being developed. Some of these systems have employed MEMS deformable mirrors as their active corrective element. More recent work in AO for astronomical applications has focused on providing correction in more than one conjugate plane. Additionally, horizontal path AO systems are exploring correction in multiple conjugate planes. This provides challenges for a laboratory system as the aberrations need to be generated and corrected in more than one plane in the optical system. Our work with compact AO systems employing MEMS technology in addition to liquid crystal spatial light modulator (SLM) driven aberration generators has been scaled up to a two conjugate plane testbed. Using two SLM based aberration generators and two separate wavefront sensors, the system can apply correction with two MEMS deformable mirrors. The challenges in such a system are to properly match non-identical components and weight the correction algorithm for correcting in two planes. This paper demonstrates preliminary results and analysis with this system with wavefront data and residual error measurements.

Aberrant modulation of a delayed rectifier potassium channel by glutamate in Alzheimer's disease.

PubMed

Poulopoulou, Cornelia; Markakis, Ioannis; Davaki, Panagiota; Tsaltas, Eleftheria; Rombos, Antonis; Hatzimanolis, Alexandros; Vassilopoulos, Dimitrios

2010-02-01

In Alzheimer's disease (AD), potassium channel abnormalities have been reported in both neural and peripheral tissues. Herein, using whole-cell patch-clamp, we demonstrate an aberrant glutamate-dependent modulation of K(V)1.3 channels in T lymphocytes of AD patients. Although intrinsic K(V)1.3 properties in patients were similar to healthy individuals, glutamate (1-1000 microM) failed to yield the hyperpolarizing shift normally observed in K(V)1.3 steady-state inactivation (-4.4+/-2.7 mV in AD vs. -14.3+/-2.5 mV in controls, 10 microM glutamate), resulting in a 4-fold increase of resting channel activity. Specific agonist and antagonist data indicate that this abnormality is due to dysfunction of cognate group II mGluRs. Given that glutamate is present in plasma and that both mGluRs and K(V)1.3 channels regulate T-lymphocyte responsiveness, our finding may account for the presence of immune-associated alterations in AD. Furthermore, if this aberration reflects a corresponding one in neural tissue, it could provide a potential target in AD pathogenesis.

Luminopsins integrate opto- and chemogenetics by using physical and biological light sources for opsin activation

PubMed Central

Berglund, Ken; Clissold, Kara; Li, Haofang E.; Wen, Lei; Park, Sung Young; Gleixner, Jan; Klein, Marguerita E.; Lu, Dongye; Barter, Joseph W.; Rossi, Mark A.; Augustine, George J.; Yin, Henry H.; Hochgeschwender, Ute

2016-01-01

Luminopsins are fusion proteins of luciferase and opsin that allow interrogation of neuronal circuits at different temporal and spatial resolutions by choosing either extrinsic physical or intrinsic biological light for its activation. Building on previous development of fusions of wild-type Gaussia luciferase with channelrhodopsin, here we expanded the utility of luminopsins by fusing bright Gaussia luciferase variants with either channelrhodopsin to excite neurons (luminescent opsin, LMO) or a proton pump to inhibit neurons (inhibitory LMO, iLMO). These improved LMOs could reliably activate or silence neurons in vitro and in vivo. Expression of the improved LMO in hippocampal circuits not only enabled mapping of synaptic activation of CA1 neurons with fine spatiotemporal resolution but also could drive rhythmic circuit excitation over a large spatiotemporal scale. Furthermore, virus-mediated expression of either LMO or iLMO in the substantia nigra in vivo produced not only the expected bidirectional control of single unit activity but also opposing effects on circling behavior in response to systemic injection of a luciferase substrate. Thus, although preserving the ability to be activated by external light sources, LMOs expand the use of optogenetics by making the same opsins accessible to noninvasive, chemogenetic control, thereby allowing the same probe to manipulate neuronal activity over a range of spatial and temporal scales. PMID:26733686

Time-course analysis of the neuroanatomical correlates of sexual arousal evoked by erotic video stimuli in healthy males.

PubMed

Sundaram, Thirunavukkarasu; Jeong, Gwang-Woo; Kim, Tae-Hoon; Kim, Gwang-Won; Baek, Han-Su; Kang, Heoung-Keun

2010-01-01

To assess the dynamic activations of the key brain areas associated with the time-course of the sexual arousal evoked by visual sexual stimuli in healthy male subjects. Fourteen right-handed heterosexual male volunteers participated in this study. Alternatively combined rest period and erotic video visual stimulation were used according to the standard block design. In order to illustrate and quantify the spatiotemporal activation patterns of the key brain regions, the activation period was divided into three different stages as the EARLY, MID and LATE stages. For the group result (p < 0.05), when comparing the MID stage with the EARLY stage, a significant increase of the brain activation was observed in the areas that included the inferior frontal gyrus, the supplementary motor area, the hippocampus, the head of the caudate nucleus, the midbrain, the superior occipital gyrus and the fusiform gyrus. At the same time, when comparing the EARLY stage with the MID stage, the putamen, the globus pallidus, the pons, the thalamus, the hypothalamus, the lingual gyrus and the cuneus yielded significantly increased activations. When comparing the LATE stage with the MID stage, all the above mentioned brain regions showed elevated activations except the hippocampus. Our results illustrate the spatiotemporal activation patterns of the key brain regions across the three stages of visual sexual arousal.

Time-Course Analysis of the Neuroanatomical Correlates of Sexual Arousal Evoked by Erotic Video Stimuli in Healthy Males

PubMed Central

Sundaram, Thirunavukkarasu; Kim, Tae-Hoon; Kim, Gwang-Won; Baek, Han-Su; Kang, Heoung-Keun

2010-01-01

Objective To assess the dynamic activations of the key brain areas associated with the time-course of the sexual arousal evoked by visual sexual stimuli in healthy male subjects. Materials and Methods Fourteen right-handed heterosexual male volunteers participated in this study. Alternatively combined rest period and erotic video visual stimulation were used according to the standard block design. In order to illustrate and quantify the spatiotemporal activation patterns of the key brain regions, the activation period was divided into three different stages as the EARLY, MID and LATE stages. Results For the group result (p < 0.05), when comparing the MID stage with the EARLY stage, a significant increase of the brain activation was observed in the areas that included the inferior frontal gyrus, the supplementary motor area, the hippocampus, the head of the caudate nucleus, the midbrain, the superior occipital gyrus and the fusiform gyrus. At the same time, when comparing the EARLY stage with the MID stage, the putamen, the globus pallidus, the pons, the thalamus, the hypothalamus, the lingual gyrus and the cuneus yielded significantly increased activations. When comparing the LATE stage with the MID stage, all the above mentioned brain regions showed elevated activations except the hippocampus. Conclusion Our results illustrate the spatiotemporal activation patterns of the key brain regions across the three stages of visual sexual arousal. PMID:20461181

Radiation-Induced Chromosomal Aberrations and Immunotherapy: Micronuclei, Cytosolic DNA, and Interferon-Production Pathway.

PubMed

Durante, Marco; Formenti, Silvia C

2018-01-01

Radiation-induced chromosomal aberrations represent an early marker of late effects, including cell killing and transformation. The measurement of cytogenetic damage in tissues, generally in blood lymphocytes, from patients treated with radiotherapy has been studied for many years to predict individual sensitivity and late morbidity. Acentric fragments are lost during mitosis and create micronuclei (MN), which are well correlated to cell killing. Immunotherapy is rapidly becoming a most promising new strategy for metastatic tumors, and combination with radiotherapy is explored in several pre-clinical studies and clinical trials. Recent evidence has shown that the presence of cytosolic DNA activates immune response via the cyclic GMP-AMP synthase/stimulator of interferon genes pathway, which induces type I interferon transcription. Cytosolic DNA can be found after exposure to ionizing radiation either as MN or as small fragments leaking through nuclear envelope ruptures. The study of the dependence of cytosolic DNA and MN on dose and radiation quality can guide the optimal combination of radiotherapy and immunotherapy. The role of densely ionizing charged particles is under active investigation to define their impact on the activation of the interferon pathway.

Aberrant Cortical Activity in Multiple GCaMP6-Expressing Transgenic Mouse Lines

PubMed Central

Buetfering, Christina; Groblewski, Peter A.; Manavi, Sahar; Miles, Jesse; White, Casey; Griffin, Fiona; Roll, Kate; Cross, Sissy; Nguyen, Thuyanh V.; Larsen, Rachael; Daigle, Tanya; Thompson, Carol L.; Olsen, Shawn; Hausser, Michael

2017-01-01

Abstract Transgenic mouse lines are invaluable tools for neuroscience but, as with any technique, care must be taken to ensure that the tool itself does not unduly affect the system under study. Here we report aberrant electrical activity, similar to interictal spikes, and accompanying fluorescence events in some genotypes of transgenic mice expressing GCaMP6 genetically encoded calcium sensors. These epileptiform events have been observed particularly, but not exclusively, in mice with Emx1-Cre and Ai93 transgenes, of either sex, across multiple laboratories. The events occur at >0.1 Hz, are very large in amplitude (>1.0 mV local field potentials, >10% df/f widefield imaging signals), and typically cover large regions of cortex. Many properties of neuronal responses and behavior seem normal despite these events, although rare subjects exhibit overt generalized seizures. The underlying mechanisms of this phenomenon remain unclear, but we speculate about possible causes on the basis of diverse observations. We encourage researchers to be aware of these activity patterns while interpreting neuronal recordings from affected mouse lines and when considering which lines to study. PMID:28932809

Nodal aberration theory applied to freeform surfaces

NASA Astrophysics Data System (ADS)

Fuerschbach, Kyle; Rolland, Jannick P.; Thompson, Kevin P.

2014-12-01

When new three-dimensional packages are developed for imaging optical systems, the rotational symmetry of the optical system is often broken, changing its imaging behavior and making the optical performance worse. A method to restore the performance is to use freeform optical surfaces that compensate directly the aberrations introduced from tilting and decentering the optical surfaces. In order to effectively optimize the shape of a freeform surface to restore optical functionality, it is helpful to understand the aberration effect the surface may induce. Using nodal aberration theory the aberration fields induced by a freeform surface in an optical system are explored. These theoretical predications are experimentally validated with the design and implementation of an aberration generating telescope.

Aberrant Recapitulation of Developmental Program: Novel Target in Scleroderma

DTIC Science & Technology

2015-12-01

promoter hypermethylation in systemic sclerosis. Annals of the rheumatic diseases . 2014;73:1232-1239) ...can prevent or attenuate fibrosis in scleroderma, and to ascertain whether markers of -catenin signaling can be used as biomarkers of disease activity...and disease subtype, FVC, DLCO and PAP will be analyzed by linear regression. (Months 1-12) We have successfully measured Wnt activity using LSL

Aberrant phosphorylation of SMAD4 Thr277-mediated USP9x-SMAD4 interaction by free fatty acids promotes breast cancer metastasis

PubMed Central

Wu, Yong; Yu, Xiaoting; Yi, Xianghua; Wu, Ke; Dwabe, Sami; Atefi, Mohammad; Elshimali, Yahya; Kemp, Kevin T.; Bhat, Kruttika; Haro, Jesse; Sarkissyan, Marianna; Vadgama, Jaydutt V

2017-01-01

Obesity increases the risk of distant metastatic recurrence and reduces breast cancer (BC) survival. However, the mechanisms behind this pathology and identification of relevant therapeutic targets are poorly defined. Plasma free fatty acids (FFA) levels are elevated in obese individuals. Here we report that TGF-β transiently activates ERK and subsequently phosphorylates SMAD4 at Thr277, which facilitates a SMAD4-USP9x interaction, SMAD4 nuclear retention, and stimulates TGF-β /SMAD3-mediated transcription of Twist and Snail. USP9x inhibited the E3 ubiquitin-protein ligase TIF1γ from binding and monoubiquitinating SMAD4, hence maintaining SMAD4 nuclear retention. FFA further facilitated TGF-β-induced ERK activation, SMAD4 phosphorylation and nuclear retention, promoting TGF-β-dependent cancer progression. Inhibition of ERK and USP9x suppressed obesity-induced metastasis. Additionally, clinical data indicated that phospho-ERK and -SMAD4 levels correlate with activated TGF-β signaling and metastasis in overweight/obese patient BC specimens. Altogether, we demonstrate the vital interaction of USP9x and SMAD4 for governing TGF-β signaling and dyslipidemia-induced, aberrant TGF-β activation during BC metastasis. PMID:28115363

Aberrant Modulation of Brain Oscillatory Activity and Attentional Impairment in Attention-Deficit/Hyperactivity Disorder.

PubMed

Lenartowicz, Agatha; Mazaheri, Ali; Jensen, Ole; Loo, Sandra K

2018-01-01

Electroencephalography and magnetoencephalography are noninvasive neuroimaging techniques that have been used extensively to study various resting-state and cognitive processes in the brain. The purpose of this review is to highlight a number of recent studies that have investigated the alpha band (8-12 Hz) oscillatory activity present in magnetoencephalography and electroencephalography, to provide new insights into the maladaptive network activity underlying attentional impairments in attention-deficit/hyperactivity disorder (ADHD). Studies reviewed demonstrate that event-related decrease in alpha is attenuated during visual selective attention, primarily in ADHD inattentive type, and is often significantly associated with accuracy and reaction time during task performance. Furthermore, aberrant modulation of alpha activity has been reported across development and may have abnormal or atypical lateralization patterns in ADHD. Modulations in the alpha band thus represent a robust, relatively unexplored putative biomarker of attentional impairment and a strong prospect for future studies aimed at examining underlying neural mechanisms and treatment response among individuals with ADHD. Potential limitations of its use as a diagnostic biomarker and directions for future research are discussed. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

The spatio-temporal dynamics of PKA activity profile during mitosis and its correlation to chromosome segregation.

PubMed

Vandame, Pauline; Spriet, Corentin; Trinel, Dave; Gelaude, Armance; Caillau, Katia; Bompard, Coralie; Biondi, Emanuele; Bodart, Jean-François

2014-01-01

The cyclic adenosine monophosphate dependent kinase protein (PKA) controls a variety of cellular processes including cell cycle regulation. Here, we took advantages of genetically encoded FRET-based biosensors, using an AKAR-derived biosensor to characterize PKA activity during mitosis in living HeLa cells using a single-cell approach. We measured PKA activity changes during mitosis. HeLa cells exhibit a substantial increase during mitosis, which ends with telophase. An AKAREV T>A inactive form of the biosensor and H89 inhibitor were used to ascertain for the specificity of the PKA activity measured. On a spatial point of view, high levels of activity near to chromosomal plate during metaphase and anaphase were detected. By using the PKA inhibitor H89, we assessed the role of PKA in the maintenance of a proper division phenotype. While this treatment in our hands did not impaired cell cycle progression in a drastic manner, inhibition of PKA leads to a dramatic increase in chromososme misalignement on the spindle during metaphase that could result in aneuploidies. Our study emphasizes the insights that can be gained with genetically encoded FRET-based biosensors, which enable to overcome the shortcomings of classical methologies and unveil in vivo PKA spatiotemporal profiles in HeLa cells.

Wavefront measurement using computational adaptive optics.

PubMed

South, Fredrick A; Liu, Yuan-Zhi; Bower, Andrew J; Xu, Yang; Carney, P Scott; Boppart, Stephen A

2018-03-01

In many optical imaging applications, it is necessary to correct for aberrations to obtain high quality images. Optical coherence tomography (OCT) provides access to the amplitude and phase of the backscattered optical field for three-dimensional (3D) imaging samples. Computational adaptive optics (CAO) modifies the phase of the OCT data in the spatial frequency domain to correct optical aberrations without using a deformable mirror, as is commonly done in hardware-based adaptive optics (AO). This provides improvement of image quality throughout the 3D volume, enabling imaging across greater depth ranges and in highly aberrated samples. However, the CAO aberration correction has a complicated relation to the imaging pupil and is not a direct measurement of the pupil aberrations. Here we present new methods for recovering the wavefront aberrations directly from the OCT data without the use of hardware adaptive optics. This enables both computational measurement and correction of optical aberrations.

Binocular adaptive optics visual simulator.

PubMed

Fernández, Enrique J; Prieto, Pedro M; Artal, Pablo

2009-09-01

A binocular adaptive optics visual simulator is presented. The instrument allows for measuring and manipulating ocular aberrations of the two eyes simultaneously, while the subject performs visual testing under binocular vision. An important feature of the apparatus consists on the use of a single correcting device and wavefront sensor. Aberrations are controlled by means of a liquid-crystal-on-silicon spatial light modulator, where the two pupils of the subject are projected. Aberrations from the two eyes are measured with a single Hartmann-Shack sensor. As an example of the potential of the apparatus for the study of the impact of the eye's aberrations on binocular vision, results of contrast sensitivity after addition of spherical aberration are presented for one subject. Different binocular combinations of spherical aberration were explored. Results suggest complex binocular interactions in the presence of monochromatic aberrations. The technique and the instrument might contribute to the better understanding of binocular vision and to the search for optimized ophthalmic corrections.

Characteristics, processes, and causes of the spatio-temporal variabilities of the East Asian monsoon system

NASA Astrophysics Data System (ADS)

Huang, Ronghui; Chen, Jilong; Wang, Lin; Lin, Zhongda

2012-09-01

Recent advances in the study of the characteristics, processes, and causes of spatio-temporal variabilities of the East Asian monsoon (EAM) system are reviewed in this paper. The understanding of the EAM system has improved in many aspects: the basic characteristics of horizontal and vertical structures, the annual cycle of the East Asian summer monsoon (EASM) system and the East Asian winter monsoon (EAWM) system, the characteristics of the spatio-temporal variabilities of the EASM system and the EAWM system, and especially the multiple modes of the EAM system and their spatio-temporal variabilities. Some new results have also been achieved in understanding the atmosphere-ocean interaction and atmosphere-land interaction processes that affect the variability of the EAM system. Based on recent studies, the EAM system can be seen as more than a circulation system, it can be viewed as an atmosphere-ocean-land coupled system, namely, the EAM climate system. In addition, further progress has been made in diagnosing the internal physical mechanisms of EAM climate system variability, especially regarding the characteristics and properties of the East Asia-Pacific (EAP) teleconnection over East Asia and the North Pacific, the "Silk Road" teleconnection along the westerly jet stream in the upper troposphere over the Asian continent, and the dynamical effects of quasi-stationary planetary wave activity on EAM system variability. At the end of the paper, some scientific problems regarding understanding the EAM system variability are proposed for further study.

Early perception and structural identity: neural implementation

NASA Astrophysics Data System (ADS)

Ligomenides, Panos A.

1992-03-01

It is suggested that there exists a minimal set of rules for the perceptual composition of the unending variety of spatio-temporal patterns in our perceptual world. Driven by perceptual discernment of "sudden change" and "unexpectedness", these rules specify conditions (such as co-linearity and virtual continuation) for perceptual grouping and for recursive compositions of perceptual "modalities" and "signatures". Beginning with a smallset of primitive perceptual elements, selected contextually at some relevant level of abstraction, perceptual compositions can graduate to an unlimited variety of spatiotemporal signatures, scenes and activities. Local discernible elements, often perceptually ambiguous by themselves, may be integrated into spatiotemporal compositions, which generate unambiguous perceptual separations between "figure" and "ground". The definition of computational algorithms for the effective instantiation of the rules of perceptual grouping remains a principal problem. In this paper we present our approach for solving the problem of perceptual recognition within the confines of one-D variational profiles. More specifically, concerning "early" (pre-attentive) recognition, we define the "structural identity of a k-norm, k ∈ K,"--SkID--as a tool for discerning and locating the instantiation of spatiotemporal objects or events. The SkID profile also serves a s a reference coordinate framework for the "perceptual focusing of attention" and the eventual assessment of resemblance. Neural network implementations of pre-attentive and attentive recognition are also discussed briefly. Our principles are exemplified by application to one-D perceptual profiles, which allows simplicity of definitions and of the rules of perceptual composition.

Persistence of Early Emerging Aberrant Behavior in Children with Developmental Disabilities

ERIC Educational Resources Information Center

Green, Vanessa A.; O'Reilly, Mark; Itchon, Jonathan; Sigafoos, Jeff

2005-01-01

This study examined the persistence of early emerging aberrant behavior in 13 preschool children with developmental disabilities. The severity of aberrant behavior was assessed every 6 months over a 3-year period. Teachers completed the assessments using the Aberrant Behavior Checklist [Aman, M. G., & Singh, N. N. (1986). "Aberrant…

Aberration corrected STEM by means of diffraction gratings

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

Linck, Martin; Ercius, Peter A.; Pierce, Jordan S.

In the past 15 years, the advent of aberration correction technology in electron microscopy has enabled materials analysis on the atomic scale. This is made possible by precise arrangements of multipole electrodes and magnetic solenoids to compensate the aberrations inherent to any focusing element of an electron microscope. In this paper, we describe an alternative method to correct for the spherical aberration of the objective lens in scanning transmission electron microscopy (STEM) using a passive, nanofabricated diffractive optical element. This holographic device is installed in the probe forming aperture of a conventional electron microscope and can be designed to removemore » arbitrarily complex aberrations from the electron's wave front. In this work, we show a proof-of-principle experiment that demonstrates successful correction of the spherical aberration in STEM by means of such a grating corrector (GCOR). Our GCOR enables us to record aberration-corrected high-resolution high-angle annular dark field (HAADF-) STEM images, although yet without advancement in probe current and resolution. Finally, improvements in this technology could provide an economical solution for aberration-corrected high-resolution STEM in certain use scenarios.« less

Double-pass measurement of human eye aberrations: limitations and practical realization

NASA Astrophysics Data System (ADS)

Letfullin, Renat R.; Belyakov, Alexey I.; Cherezova, Tatyana Y.; Kudryashov, Alexis V.

2004-11-01

The problem of correct eye aberrations measurement is very important with the rising widespread of a surgical procedure for reducing refractive error in the eye, so called, LASIK (laser-assisted in situ keratomileusis). The double-pass technique commonly used for measuring aberrations of a human eye involves some uncertainties. One of them is loosing the information about odd human eye aberrations. We report about investigations of the applicability limit of the double-pass measurements depending upon the aberrations status introduced by human eye and actual size of the entrance pupil. We evaluate the double-pass effects for various aberrations and different pupil diameters. It is shown that for small pupils the double-pass effects are negligible. The testing and alignment of aberrometer was performed using the schematic eye, developed in our lab. We also introduced a model of human eye based on bimorph flexible mirror. We perform calculations to demonstrate that our schematic eye is capable of reproducing spatial-temporal statistics of aberrations of living eye with normal vision or even myopic or hypermetropic or with high aberrations ones.

Aberration corrected STEM by means of diffraction gratings

DOE PAGES

Linck, Martin; Ercius, Peter A.; Pierce, Jordan S.; ...

2017-06-12

In the past 15 years, the advent of aberration correction technology in electron microscopy has enabled materials analysis on the atomic scale. This is made possible by precise arrangements of multipole electrodes and magnetic solenoids to compensate the aberrations inherent to any focusing element of an electron microscope. In this paper, we describe an alternative method to correct for the spherical aberration of the objective lens in scanning transmission electron microscopy (STEM) using a passive, nanofabricated diffractive optical element. This holographic device is installed in the probe forming aperture of a conventional electron microscope and can be designed to removemore » arbitrarily complex aberrations from the electron's wave front. In this work, we show a proof-of-principle experiment that demonstrates successful correction of the spherical aberration in STEM by means of such a grating corrector (GCOR). Our GCOR enables us to record aberration-corrected high-resolution high-angle annular dark field (HAADF-) STEM images, although yet without advancement in probe current and resolution. Finally, improvements in this technology could provide an economical solution for aberration-corrected high-resolution STEM in certain use scenarios.« less

Chromosomal aberrations in 2000 couples of Indian ethnicity with reproductive failure.

PubMed

Gada Saxena, S; Desai, K; Shewale, L; Ranjan, P; Saranath, D

2012-08-01

Constitutional chromosomal aberrations contribute to infertility and repeated miscarriage leading to reproductive failure in couples. These aberrations may show no obvious clinical manifestations and remain undetected across multiple generations. However, infertility or recurrent spontaneous pregnancy loss, and/or genotypic/phenotypic aberrations may be manifested in the progeny during gametogenesis. The current study was a retrospective analysis to examine the chromosomal aberrations and prevalence in 2000 couples of Indian ethnicity with reproductive failure. Cytogenetic analysis via conventional G-band karyotyping analysis was carried out on phytohaemagglutinin stimulated peripheral blood lymphocytes, cultured in RPMI1640 medium. The chromosomes were enumerated as per International System for Human Cytogenetic Nomenclature at 500-550 band resolution, and recorded in the screening sheets. Chromosomal aberrations were detected in a total of 110 (2.78%) couples, with structural chromosomal aberrations in 88 cases including reciprocal translocations in 56 cases, Robertsonian translocations in 16 cases, inversions in eight cases, deletions in three cases, derivative chromosomes in five cases and numerical chromosome aberrations in 23 cases. The study emphasizes the importance of cytogenetic work up in both the partners associated with a history of reproductive failure. Genetic counselling with an option of prenatal diagnosis should be offered to couples with chromosomal aberrations. Copyright © 2012 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Effect of monochromatic aberrations on photorefractive patterns

NASA Astrophysics Data System (ADS)

Campbell, Melanie C. W.; Bobier, W. R.; Roorda, A.

1995-08-01

Photorefractive methods have become popular in the measurement of refractive and accommodative states of infants and children owing to their photographic nature and rapid speed of measurement. As in the case of any method that measures the refractive state of the human eye, monochromatic aberrations will reduce the accuracy of the measurement. Monochromatic aberrations cannot be as easily predicted or controlled as chromatic aberrations during the measurement, and accordingly they will introduce measurement errors. This study defines this error or uncertainty by extending the existing paraxial optical analyses of coaxial and eccentric photorefraction. This new optical analysis predicts that, for the amounts of spherical aberration (SA) reported for the human eye, there will be a significant degree of measurement uncertainty introduced for all photorefractive methods. The dioptric amount of this uncertainty may exceed the maximum amount of SA present in the eye. The calculated effects on photorefractive measurement of a real eye with a mixture of spherical aberration and coma are shown to be significant. The ability, developed here, to predict photorefractive patterns corresponding to different amounts and types of monochromatic aberration may in the future lead to an extension of photorefractive methods to the dual measurement of refractive states and aberrations of individual eyes. aberration, retinal image quality,

Aberration compensation of an ultrasound imaging instrument with a reduced number of channels.

PubMed

Jiang, Wei; Astheimer, Jeffrey P; Waag, Robert C

2012-10-01

Focusing and imaging qualities of an ultrasound imaging system that uses aberration correction were experimentally investigated as functions of the number of parallel channels. Front-end electronics that consolidate signals from multiple physical elements can be used to lower hardware and computational costs by reducing the number of parallel channels. However, the signals from sparse arrays of synthetic elements yield poorer aberration estimates. In this study, aberration estimates derived from synthetic arrays of varying element sizes are evaluated by comparing compensated receive focuses, compensated transmit focuses, and compensated b-scan images of a point target and a cyst phantom. An array of 80 x 80 physical elements with a pitch of 0.6 x 0.6 mm was used for all of the experiments and the aberration was produced by a phantom selected to mimic propagation through abdominal wall. The results show that aberration correction derived from synthetic arrays with pitches that have a diagonal length smaller than 70% of the correlation length of the aberration yield focuses and images of approximately the same quality. This connection between correlation length of the aberration and synthetic element size provides a guideline for determining the number of parallel channels that are required when designing imaging systems that employ aberration correction.

Statistical estimation of ultrasonic propagation path parameters for aberration correction.

PubMed

Waag, Robert C; Astheimer, Jeffrey P

2005-05-01

Parameters in a linear filter model for ultrasonic propagation are found using statistical estimation. The model uses an inhomogeneous-medium Green's function that is decomposed into a homogeneous-transmission term and a path-dependent aberration term. Power and cross-power spectra of random-medium scattering are estimated over the frequency band of the transmit-receive system by using closely situated scattering volumes. The frequency-domain magnitude of the aberration is obtained from a normalization of the power spectrum. The corresponding phase is reconstructed from cross-power spectra of subaperture signals at adjacent receive positions by a recursion. The subapertures constrain the receive sensitivity pattern to eliminate measurement system phase contributions. The recursion uses a Laplacian-based algorithm to obtain phase from phase differences. Pulse-echo waveforms were acquired from a point reflector and a tissue-like scattering phantom through a tissue-mimicking aberration path from neighboring volumes having essentially the same aberration path. Propagation path aberration parameters calculated from the measurements of random scattering through the aberration phantom agree with corresponding parameters calculated for the same aberrator and array position by using echoes from the point reflector. The results indicate the approach describes, in addition to time shifts, waveform amplitude and shape changes produced by propagation through distributed aberration under realistic conditions.

The Distribution of Chromosomal Aberrations in Human Cells Predicted by a Generalized Time-Dependent Model of Radiation-Induced Formation of Aberrations

NASA Technical Reports Server (NTRS)

Ponomarev, Artem L.; George, K.; Cucinotta, F. A.

2011-01-01

New experimental data show how chromosomal aberrations for low- and high-LET radiation are dependent on DSB repair deficiencies in wild-type, AT and NBS cells. We simulated the development of chromosomal aberrations in these cells lines in a stochastic track-structure-dependent model, in which different cells have different kinetics of DSB repair. We updated a previously formulated model of chromosomal aberrations, which was based on a stochastic Monte Carlo approach, to consider the time-dependence of DSB rejoining. The previous version of the model had an assumption that all DSBs would rejoin, and therefore we called it a time-independent model. The chromosomal-aberrations model takes into account the DNA and track structure for low- and high-LET radiations, and provides an explanation and prediction of the statistics of rare and more complex aberrations. We compared the program-simulated kinetics of DSB rejoining to the experimentally-derived bimodal exponential curves of the DSB kinetics. We scored the formation of translocations, dicentrics, acentric and centric rings, deletions, and inversions. The fraction of DSBs participating in aberrations was studied in relation to the rejoining time. Comparisons of simulated dose dependence for simple aberrations to the experimental dose-dependence for HF19, AT and NBS cells will be made.

Expression of AID, P53, and Mlh1 proteins in endoscopically resected differentiated-type early gastric cancer

PubMed Central

Takeda, Yohei; Yashima, Kazuo; Hayashi, Akihiro; Sasaki, Shuji; Kawaguchi, Koichiro; Harada, Kenichi; Murawaki, Yoshikazu; Ito, Hisao

2012-01-01

AIM: To analyze the expression of the tumor-related proteins in differentiated-type early gastric carcinoma (DEGC) samples. METHODS: Tumor specimens were obtained from 102 patients (75 males and 27 females) who had received an endoscopic tumor resection at Tottori University Hospital between 2007 and 2009. Ninety-one cancer samples corresponded to noninvasive or intramucosal carcinoma according to the Vienna classification system, and 11 samples were submucosal invasive carcinomas. All of the EGCs were histologically differentiated carcinomas. All patients were classified as having Helicobacter pylori (H. pylori) infections by endoscopic atrophic changes or by testing seropositive for H. pylori IgG. All of the samples were histopathologically classified as either tubular or papillary adenocarcinoma according to their structure. The immunohistochemical staining was performed in a blinded manner with respect to the clinical information. Two independent observers evaluated protein expression. All data were statistically analyzed then. RESULTS: The rates of aberrant activation-induced cytidine deaminase (AID) expression and P53 overexpression were both 34.3% in DEGCs. The expression of Mlh1 was lost in 18.6% of DEGCs. Aberrant AID expression was not significantly associated with P53 overexpression in DEGCs. However, AID expression was associated with the severity of mononuclear cell activity in the non-cancerous mucosa adjacent to the tumor (P = 0.064). The rate of P53 expression was significantly greater in flat or depressed tumors than in elevated tumors. The frequency of Mlh1 loss was significantly increased in distal tumors, elevated gross-type tumors, papillary histological-type tumors, and tumors with a severe degree of endoscopic atrophic gastritis (P < 0.05). CONCLUSION: Aberrant AID expression, P53 overexpression, and the loss of Mlh1 were all associated with clinicopathological features and gastric mucosal alterations in DEGCs. The aberrant expression of AID protein may partly contribute to the induction of nuclear P53 expression. PMID:22737274

NKL homeobox gene MSX1 acts like a tumor suppressor in NK-cell leukemia

PubMed Central

Nagel, Stefan; Pommerenke, Claudia; Meyer, Corinna; Kaufmann, Maren; MacLeod, Roderick A.F.; Drexler, Hans G.

2017-01-01

NKL homeobox gene MSX1 is physiologically expressed in lymphoid progenitors and subsequently downregulated in developing T- and B-cells. In contrast, elevated expression levels of MSX1 persist in mature natural killer (NK)-cells, indicating a functional role in this compartment. While T-cell acute lymphoblastic leukemia (T-ALL) subsets exhibit aberrant overexpression of MSX1, we show here that in malignant NK-cells the level of MSX1 transcripts is aberrantly downregulated. Chromosomal deletions at 4p16 hosting the MSX1 locus have been described in NK-cell leukemia patients. However, NK-cell lines analyzed here showed normal MSX1 gene configurations, indicating that this aberration might be uncommon. To identify alternative MSX1 regulatory mechanisms we compared expression profiling data of primary normal NK-cells and malignant NK-cell lines. This procedure revealed several deregulated genes including overexpressed IRF4, MIR155HG and MIR17HG and downregulated AUTS2, EP300, GATA3 and HHEX. As shown recently, chromatin-modulator AUTS2 is overexpressed in T-ALL subsets where it mediates aberrant transcriptional activation of MSX1. Here, our data demonstrate that in malignant NK-cell lines AUTS2 performed MSX1 activation as well, but in accordance with downregulated MSX1 transcription therein we detected reduced AUTS2 expression, a small genomic deletion at 7q11 removing exons 3 and 4, and truncating mutations in exon 1. Moreover, genomic profiling and chromosomal analyses of NK-cell lines demonstrated amplification of IRF4 at 6p25 and deletion of PRDM1 at 6q21, highlighting their potential oncogenic impact. Functional analyses performed via knockdown or forced expression of these genes revealed regulatory network disturbances effecting downregulation of MSX1 which may underlie malignant development in NK-cells. PMID:28977998

Plum polyphenols inhibit colorectal aberrant crypt foci formation in rats: potential role of the miR-143/protein kinase B/mammalian target of rapamycin axis.

PubMed

Banerjee, Nivedita; Kim, Hyemee; Talcott, Stephen T; Turner, Nancy D; Byrne, David H; Mertens-Talcott, Susanne U

2016-10-01

The nutritional prevention of aberrant crypt foci by polyphenols may be a crucial step to dietary cancer prevention. The objective of this study was to determine the underlying mechanisms that contribute to the anti-inflammatory and antitumorigenic properties of plum (Prunus salicina L.) polyphenols, including chlorogenic acid and neochlorogenic acid, in azoxymethane (AOM)-treated rats. The hypothesis was that plum polyphenolics suppress AOM-induced aberrant crypt foci formation through alterations in the protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway and relative micro-RNA expressions. Sprague-Dawley rats (n=10/group) received plum beverage (1346mg gallic acid equivalents/L) or a control beverage ad libitum for 10 weeks with subcutaneous injections of AOM (15mg/kg) at weeks 2 and 3. Results show that the consumption of the plum beverage decreased the number of dysplastic aberrant crypt foci by 48% (P<.05) and lowered proliferation of mucosal cells by 24% (P<.05). The plum beverage decreased the activity of glutathione peroxidase, superoxide dismutase, and catalase in mucosal scrapings, as well as the superoxide dismutase activity in serum. The results were accompanied by a down-regulation of proinflammatory enzymes nuclear factor κB, nitric oxide synthase, cyclooxygenase-2, and vascular cell adhesion molecule 1 messenger RNA. Plum inhibited the expression of AKT and mTOR messenger RNA, phosphorylated AKT, mTOR, and hypoxia-inducible factor-1α protein levels, and the ratio of the phosphorylated/total protein expression of mTOR. Also, the plum beverage increased the expression of miR-143, which is involved in the regulation of AKT. These results suggest that plum polyphenols may exhibit a chemopreventive potential against colon carcinogenesis by impacting the AKT/mTOR pathway and miR-143. Copyright © 2016 Elsevier Inc. All rights reserved.

Transitionality in addiction: A "temporal continuum" hypotheses involving the aberrant motivation, the hedonic dysregulation, and the aberrant learning.

PubMed

Patrono, Enrico; Gasbarri, Antonella; Tomaz, Carlos; Nishijo, Hisao

2016-08-01

Addiction is a chronic compulsion and relapsing disorder. It involves several brain areas and circuits, which encode vary functions such as reward, motivation, and memory. Drug addiction is defined as a "pathological pattern of use of a substance", characterized by the loss of control on drug-taking-related behaviors, the pursuance of those behaviors even in the presence of negative consequences, and a strong motivated activity to assume substances. Three different theories guide experimental research on drug addiction. Each of these theories consider singles features, such as an aberrant motivation, a hedonic dysregulation, and an aberrant habit learning as the main actor to explain the entire process of the addictive behaviors. The major goal of this study is to present a new hypotheses of transitionality from a controlled use to abuse of addictive substances trough the overview of the three different theories, considering all the single features of each single theory together on the same "temporal continuum" from use to abuse of addictive substances. Recently, it has been suggested that common neural systems may be activated by natural and pharmacological stimuli, raising the hypotheses that binge-eating disorders could be considered as addictive behaviors. The second goal of this study is to present evidences in order to highlight a possible psycho-bio-physiological superimposition between drug and "food addiction". Finally, interesting questions are brought up starting from last findings about a theoretical/psycho-bio-physiological superimposition between drug and "food addiction" and their possibly same transitionality along the same "temporal continuum" from use to abuse of addictive substances in order to investigate new therapeutic strategies based on new therapeutic strategies based on the individual moments characterizing the transition from the voluntary intake of substances to the maladaptive addictive behavior. Copyright © 2016. Published by Elsevier Ltd.

Interpreting Chromosome Aberration Spectra

NASA Technical Reports Server (NTRS)

Levy, Dan; Reeder, Christopher; Loucas, Bradford; Hlatky, Lynn; Chen, Allen; Cornforth, Michael; Sachs, Rainer

2007-01-01

Ionizing radiation can damage cells by breaking both strands of DNA in multiple locations, essentially cutting chromosomes into pieces. The cell has enzymatic mechanisms to repair such breaks; however, these mechanisms are imperfect and, in an exchange process, may produce a large-scale rearrangement of the genome, called a chromosome aberration. Chromosome aberrations are important in killing cells, during carcinogenesis, in characterizing repair/misrepair pathways, in retrospective radiation biodosimetry, and in a number of other ways. DNA staining techniques such as mFISH ( multicolor fluorescent in situ hybridization) provide a means for analyzing aberration spectra by examining observed final patterns. Unfortunately, an mFISH observed final pattern often does not uniquely determine the underlying exchange process. Further, resolution limitations in the painting protocol sometimes lead to apparently incomplete final patterns. We here describe an algorithm for systematically finding exchange processes consistent with any observed final pattern. This algorithm uses aberration multigraphs, a mathematical formalism that links the various aspects of aberration formation. By applying a measure to the space of consistent multigraphs, we will show how to generate model-specific distributions of aberration processes from mFISH experimental data. The approach is implemented by software freely available over the internet. As a sample application, we apply these algorithms to an aberration data set, obtaining a distribution of exchange cycle sizes, which serves to measure aberration complexity. Estimating complexity, in turn, helps indicate how damaging the aberrations are and may facilitate identification of radiation type in retrospective biodosimetry.

Corneal Aberrations in Former Preterm Infants: Results From The Wiesbaden Prematurity Study.

PubMed

Fieß, Achim; Schuster, Alexander K; Kölb-Keerl, Ruth; Knuf, Markus; Kirchhof, Bernd; Muether, Philipp S; Bauer, Jacqueline

2017-12-01

To compare corneal aberrations in former preterm infants to that of full-term infants. A prospective cross-sectional study was carried out measuring the corneal shape with Scheimpflug imaging in former preterm infants of gestational age (GA) ≤32 weeks and full-term infants with GA ≥37 weeks now being aged between 4 to 10 years. The main outcome measures were corneal aberrations including astigmatism (Zernike: Z2-2; Z22), coma (Z3-1; Z31), trefoil (Z3-3; Z33), spherical aberration (Z40) and root-mean square of higher-order aberrations (RMS HOA). Multivariable analysis was performed to assess independent associations of gestational age groups and of retinopathy of prematurity (ROP) occurrence with corneal aberrations adjusting for sex and age at examination. A total of 259 former full-term and 226 preterm infants with a mean age of 7.2 ± 2.0 years were included in this study. Statistical analysis revealed an association of extreme prematurity (GA ≤28 weeks) with higher-order and lower-order aberrations of the total cornea. Vertical coma was higher in extreme prematurity (P < 0.001), due to the shape of the anterior corneal surface, while there was no association with trefoil and spherical aberration. ROP was not associated with higher-order aberrations when adjusted for gestational age group. This study demonstrated that specific corneal aberrations were associated with extreme prematurity rather than with ROP occurrence.

Spherical aberration yielding optimum visual performance: Evaluation of intraocular lenses using adaptive optics simulation

PubMed Central

Werner, John S.; Elliott, Sarah L.; Choi, Stacey S.; Doble, Nathan

2009-01-01

PURPOSE To evaluate the influence of spherical aberration on contrast sensitivity using adaptive optics. SETTING Vision Science and Advanced Retinal Imaging Laboratory, Department of Ophthalmology & Vision Science, University of California, Davis Medical Center, Sacramento, California, USA. METHODS Contrast sensitivity at 8 cycles per degree was evaluated using an adaptive optics system that permitted aberrations to be measured with a Shack-Hartman wavefront sensor and controlled by a 109 actuator continuous-surface deformable mirror that was at a plane conjugate to the observer’s pupil. Vertical Gabor patches were viewed through a 6.3 mm diameter pupil conjugate aperture. Contrast sensitivity was measured with the deformable mirror set to produce 1 of 5 spherical aberration profiles (−0.2 to +0.2 μm). Contrast sensitivity over the range of spherical aberration was fitted with a polynomial function. RESULTS Three observers (age 21 to 24 years) participated. The measured total mean spherical aberration resulting from the spherical aberration profiles produced by the deformable mirror was between −0.15 μm and +0.25 μm. The peak contrast sensitivity of this function for the 3 observers combined occurred at +0.06 μm of spherical aberration. The peak contrast sensitivity was also achieved with positive spherical aberration for observer (mean 0.09). CONCLUSION There was intersubject variability in the measurements; however, the average visual performance was best with the introduction of a small positive spherical aberration. PMID:19545813

Aberration-free intraocular lenses - What does this really mean?

PubMed

Langenbucher, Achim; Schröder, Simon; Cayless, Alan; Eppig, Timo

2017-09-01

So-called aberration-free intraocular lenses (IOLs) are well established in modern cataract surgery. Usually, they are designed to perfectly refract a collimated light beam onto the focal point. We show how much aberration can be expected with such an IOL in a convergent light beam such as that found anterior to the human cornea. Additionally, the aberration in a collimated beam is estimated for an IOL that has no aberrations in the convergent beam. The convergent beam is modelled as the pencil of rays corresponding to the spherical wavefront resulting from a typical corneal power of 43m -1 . The IOLs are modelled as infinitely thin phase plates with 20m -1 optical power placed 5mm behind the cornea. Their aberrations are reported in terms of optical path length difference and longitudinal spherical aberration (LSA) of the marginal rays, as well as nominal spherical aberration (SA) calculated based on a Zernike representation of the wavefront-error at the corneal plane within a 6mm aperture. The IOL designed to have no aberrations in a collimated light beam has an optical path length difference of -1.8μm, and LSA of 0.15m -1 in the convergent beam of a typical eye. The corresponding nominal SA is 0.065μm. The IOL designed to have no aberrations in a convergent light beam has an optical path length difference of 1.8μm, and LSA of -0.15m -1 in the collimated beam. An IOL designed to have no aberrations in a collimated light beam will increase the SA of a patient's eye after implantation. Copyright © 2017. Published by Elsevier GmbH.

Wave aberrations in rhesus monkeys with vision-induced ametropias

PubMed Central

Ramamirtham, Ramkumar; Kee, Chea-su; Hung, Li-Fang; Qiao-Grider, Ying; Huang, Juan; Roorda, Austin; Smith, Earl L.

2007-01-01

The purpose of this study was to investigate the relationship between refractive errors and high-order aberrations in infant rhesus monkeys. Specifically, we compared the monochromatic wave aberrations measured with a Shack-Hartman wavefront sensor between normal monkeys and monkeys with vision-induced refractive errors. Shortly after birth, both normal monkeys and treated monkeys reared with optically induced defocus or form deprivation showed a decrease in the magnitude of high-order aberrations with age. However, the decrease in aberrations was typically smaller in the treated animals. Thus, at the end of the lens-rearing period, higher than normal amounts of aberrations were observed in treated eyes, both hyperopic and myopic eyes and treated eyes that developed astigmatism, but not spherical ametropias. The total RMS wavefront error increased with the degree of spherical refractive error, but was not correlated with the degree of astigmatism. Both myopic and hyperopic treated eyes showed elevated amounts of coma and trefoil and the degree of trefoil increased with the degree of spherical ametropia. Myopic eyes also exhibited a much higher prevalence of positive spherical aberration than normal or treated hyperopic eyes. Following the onset of unrestricted vision, the amount of high-order aberrations decreased in the treated monkeys that also recovered from the experimentally induced refractive errors. Our results demonstrate that high-order aberrations are influenced by visual experience in young primates and that the increase in high-order aberrations in our treated monkeys appears to be an optical byproduct of the vision-induced alterations in ocular growth that underlie changes in refractive error. The results from our study suggest that the higher amounts of wave aberrations observed in ametropic humans are likely to be a consequence, rather than a cause, of abnormal refractive development. PMID:17825347

Orthonormal aberration polynomials for anamorphic optical imaging systems with circular pupils.

PubMed

Mahajan, Virendra N

2012-06-20

In a recent paper, we considered the classical aberrations of an anamorphic optical imaging system with a rectangular pupil, representing the terms of a power series expansion of its aberration function. These aberrations are inherently separable in the Cartesian coordinates (x,y) of a point on the pupil. Accordingly, there is x-defocus and x-coma, y-defocus and y-coma, and so on. We showed that the aberration polynomials orthonormal over the pupil and representing balanced aberrations for such a system are represented by the products of two Legendre polynomials, one for each of the two Cartesian coordinates of the pupil point; for example, L(l)(x)L(m)(y), where l and m are positive integers (including zero) and L(l)(x), for example, represents an orthonormal Legendre polynomial of degree l in x. The compound two-dimensional (2D) Legendre polynomials, like the classical aberrations, are thus also inherently separable in the Cartesian coordinates of the pupil point. Moreover, for every orthonormal polynomial L(l)(x)L(m)(y), there is a corresponding orthonormal polynomial L(l)(y)L(m)(x) obtained by interchanging x and y. These polynomials are different from the corresponding orthogonal polynomials for a system with rotational symmetry but a rectangular pupil. In this paper, we show that the orthonormal aberration polynomials for an anamorphic system with a circular pupil, obtained by the Gram-Schmidt orthogonalization of the 2D Legendre polynomials, are not separable in the two coordinates. Moreover, for a given polynomial in x and y, there is no corresponding polynomial obtained by interchanging x and y. For example, there are polynomials representing x-defocus, balanced x-coma, and balanced x-spherical aberration, but no corresponding y-aberration polynomials. The missing y-aberration terms are contained in other polynomials. We emphasize that the Zernike circle polynomials, although orthogonal over a circular pupil, are not suitable for an anamorphic system as they do not represent balanced aberrations for such a system.

Ocular wavefront aberrations in the common marmoset Callithrix jacchus: effects of age and refractive error

PubMed Central

Coletta, Nancy J.; Marcos, Susana; Troilo, David

2012-01-01

The common marmoset, Callithrix jacchus, is a primate model for emmetropization studies. The refractive development of the marmoset eye depends on visual experience, so knowledge of the optical quality of the eye is valuable. We report on the wavefront aberrations of the marmoset eye, measured with a clinical Hartmann-Shack aberrometer (COAS, AMO Wavefront Sciences). Aberrations were measured on both eyes of 23 marmosets whose ages ranged from 18 to 452 days. Twenty-one of the subjects were members of studies of emmetropization and accommodation, and two were untreated normal subjects. Eleven of the 21 experimental subjects had worn monocular diffusers or occluders and ten had worn binocular spectacle lenses of equal power. Monocular deprivation or lens rearing began at about 45 days of age and ended at about 108 days of age. All refractions and aberration measures were performed while the eyes were cyclopleged; most aberration measures were made while subjects were awake, but some control measurements were performed under anesthesia. Wavefront error was expressed as a seventh-order Zernike polynomial expansion, using the Optical Society of America’s naming convention. Aberrations in young marmosets decreased up to about 100 days of age, after which the higher-order RMS aberration leveled off to about 0.10 micron over a 3 mm diameter pupil. Higher-order aberrations were 1.8 times greater when the subjects were under general anesthesia than when they were awake. Young marmoset eyes were characterized by negative spherical aberration. Visually deprived eyes of the monocular deprivation animals had greater wavefront aberrations than their fellow untreated eyes, particularly for asymmetric aberrations in the odd-numbered Zernike orders. Both lens-treated and deprived eyes showed similar significant increases in Z3-3 trefoil aberration, suggesting the increase in trefoil may be related to factors that do not involve visual feedback. PMID:20800078

Chronic Nicotine Mitigates Aberrant Inhibitory Motor Learning Induced by Motor Experience under Dopamine Deficiency

PubMed Central

Krok, Anne C.; Xu, Jian; Contractor, Anis; McGehee, Daniel S.; Zhuang, Xiaoxi

2016-01-01

Although dopamine receptor antagonism has long been associated with impairments in motor performance, more recent studies have shown that dopamine D2 receptor (D2R) antagonism, paired with a motor task, not only impairs motor performance concomitant with the pharmacodynamics of the drug, but also impairs future motor performance once antagonism has been relieved. We have termed this phenomenon “aberrant motor learning” and have suggested that it may contribute to motor symptoms in movement disorders such as Parkinson's disease (PD). Here, we show that chronic nicotine (cNIC), but not acute nicotine, treatment mitigates the acquisition of D2R-antagonist-induced aberrant motor learning in mice. Although cNIC mitigates D2R-mediated aberrant motor learning, cNIC has no effect on D1R-mediated motor learning. β2-containing nicotinic receptors in dopamine neurons likely mediate the protective effect of cNIC against aberrant motor learning, because selective deletion of β2 nicotinic subunits in dopamine neurons reduced D2R-mediated aberrant motor learning. Finally, both cNIC treatment and β2 subunit deletion blunted postsynaptic responses to D2R antagonism. These results suggest that a chronic decrease in function or a downregulation of β2-containing nicotinic receptors protects the striatal network against aberrant plasticity and aberrant motor learning induced by motor experience under dopamine deficiency. SIGNIFICANCE STATEMENT Increasingly, aberrant plasticity and aberrant learning are recognized as contributing to the development and progression of movement disorders. Here, we show that chronic nicotine (cNIC) treatment or specific deletion of β2 nicotinic receptor subunits in dopamine neurons mitigates aberrant motor learning induced by dopamine D2 receptor (D2R) blockade in mice. Moreover, both manipulations also reduced striatal dopamine release and blunt postsynaptic responses to D2R antagonists. These results suggest that chronic downregulation of function and/or receptor expression of β2-containing nicotinic receptors alters presynaptic and postsynaptic striatal signaling to protect against aberrant motor learning. Moreover, these results suggest that cNIC treatment may alleviate motor symptoms and/or delay the deterioration of motor function in movement disorders by blocking aberrant motor learning. PMID:27170121

Ocular Chromatic Aberrations and Their Effects on Polychromatic Retinal Image Quality

NASA Astrophysics Data System (ADS)

Zhang, Xiaoxiao

Previous studies of ocular chromatic aberrations have concentrated on chromatic difference of focus (CDF). Less is known about the chromatic difference of image position (CDP) in the peripheral retina and no experimental attempt has been made to measure the ocular chromatic difference of magnification (CDM). Consequently, theoretical modelling of human eyes is incomplete. The insufficient knowledge of ocular chromatic aberrations is partially responsible for two unsolved applied vision problems: (1) how to improve vision by correcting ocular chromatic aberration? (2) what is the impact of ocular chromatic aberration on the use of isoluminance gratings as a tool in spatial-color vision?. Using optical ray tracing methods, MTF analysis methods of image quality, and psychophysical methods, I have developed a more complete model of ocular chromatic aberrations and their effects on vision. The ocular CDM was determined psychophysically by measuring the tilt in the apparent frontal parallel plane (AFPP) induced by interocular difference in image wavelength. This experimental result was then used to verify a theoretical relationship between the ocular CDM, the ocular CDF and the entrance pupil of the eye. In the retinal image after correcting the ocular CDF with existing achromatizing methods, two forms of chromatic aberration (CDM and chromatic parallax) were examined. The CDM was predicted by theoretical ray tracing and measured with the same method used to determine ocular CDM. The chromatic parallax was predicted with a nodal ray model and measured with the two-color vernier alignment method. The influence of these two aberrations on polychromatic MTF were calculated. Using this improved model of ocular chromatic aberration, luminance artifacts in the images of isoluminance gratings were calculated. The predicted luminance artifacts were then compared with experimental data from previous investigators. The results show that: (1) A simple relationship exists between two major chromatic aberrations and the location of the pupil; (2) The ocular CDM is measurable and varies among individuals; (3) All existing methods to correct ocular chromatic aberration face another aberration, chromatic parallax, which is inherent in the methodology; (4) Ocular chromatic aberrations have the potential to contaminate psychophysical experimental results on human spatial-color vision.

Aberration compensation between anterior and posterior corneal surfaces after Small incision lenticule extraction and Femtosecond laser-assisted laser in-situ keratomileusis.

PubMed

Li, Xiaojing; Wang, Yan; Dou, Rui

2015-09-01

To investigate the aberration compensation between anterior and posterior corneal surfaces after SMILE and FS-LASIK. Fifty-five subjects (55 eyes) undergoing SMILE and 51 subjects (51 eyes) undergoing FS-LASIK were enrolled in this study. Wavefront aberrations of anterior and posterior corneal surfaces and the whole cornea at 6 mm in diameter were measured using a Scheimpflug Camera preoperatively and one, three and 6 months postoperatively. The compensation factor (CF), where CF = 1 - (aberration of the whole cornea/aberration of anterior corneal surface), was calculated. Spherical aberration of the posterior surface and the whole cornea remained stable after SMILE. However, spherical aberration of posterior surface increased significantly at 6 months in the FS-LASIK group. The total higher-order aberration (tHOA) of the anterior surface and the whole cornea was lower at 6 months than at one and 3 months (p = 0.001 and 0.001, respectively) in the FS-LASIK group. Meanwhile, in the SMILE group, no significant difference in tHOA was found between various postoperative time points. There were significant decreases in the CF of tHOA compared with preoperative values in both groups. The CF of spherical aberration reduced significantly in both groups at 3 and 6 mm in diameter one, three and 6 months postoperatively. Significant decreases in the CF of vertical coma were found at three and 6 months postoperatively in the FS-LASIK group compared with preoperative values at 6 mm in diameter (p = 0.021 and 0.008, respectively). The change in CF (ΔCF) of spherical aberration was smaller in the SMILE group than in the FS-LASIK group at one and 3 months postoperatively (p = 0.003 and p < 0.0001, respectively). The ΔCF of spherical aberration was significantly lower in moderately myopic subjects than in subjects with high myopia at 1 month in the SMILE group (p = 0.041) and at one, three and 6 months in the FS-LASIK group (p = 0.014, 0.020, and 0.004, respectively). The posterior corneal surface plays an important role in compensating for spherical aberration of the anterior corneal surface. The compensation mechanisms of spherical aberration and higher-order aberration between anterior and posterior corneal surfaces were disrupted by the SMILE and the FS-LASIK procedures. The change in the CF of spherical aberration was smaller in the SMILE group compared with the FS-LASIK group, especially in subjects with high myopia. © 2015 The Authors Ophthalmic & Physiological Optics © 2015 The College of Optometrists.

Test for Chemical Induction of Chromosome Aberration in Cultured Chinese Hamster Ovary (CHO) Cells With and Without Metabolic Activation. Test Article: N,N,N’,N’-tetramethyl Ethanediamine (TMEDA)

DTIC Science & Technology

2008-06-13

ACTIVATION SYSTEM The metabolic activation mixture was prepared by SITEK Research Laboratories and it consisted of phenobarbital -S,6-Benzoflavone...2147 31.0mg/mL Phenobarbital -S,6-Benzoflavone <-70°C April 19. 2009 Detailed information about the S-9 batch used ill the Assay is provided in

Neurovision processor for designing intelligent sensors

NASA Astrophysics Data System (ADS)

Gupta, Madan M.; Knopf, George K.

1992-03-01

A programmable multi-task neuro-vision processor, called the Positive-Negative (PN) neural processor, is proposed as a plausible hardware mechanism for constructing robust multi-task vision sensors. The computational operations performed by the PN neural processor are loosely based on the neural activity fields exhibited by certain nervous tissue layers situated in the brain. The neuro-vision processor can be programmed to generate diverse dynamic behavior that may be used for spatio-temporal stabilization (STS), short-term visual memory (STVM), spatio-temporal filtering (STF) and pulse frequency modulation (PFM). A multi- functional vision sensor that performs a variety of information processing operations on time- varying two-dimensional sensory images can be constructed from a parallel and hierarchical structure of numerous individually programmed PN neural processors.

A Self-Organizing Incremental Spatiotemporal Associative Memory Networks Model for Problems with Hidden State

PubMed Central

2016-01-01

Identifying the hidden state is important for solving problems with hidden state. We prove any deterministic partially observable Markov decision processes (POMDP) can be represented by a minimal, looping hidden state transition model and propose a heuristic state transition model constructing algorithm. A new spatiotemporal associative memory network (STAMN) is proposed to realize the minimal, looping hidden state transition model. STAMN utilizes the neuroactivity decay to realize the short-term memory, connection weights between different nodes to represent long-term memory, presynaptic potentials, and synchronized activation mechanism to complete identifying and recalling simultaneously. Finally, we give the empirical illustrations of the STAMN and compare the performance of the STAMN model with that of other methods. PMID:27891146

Multi-frequency localization of aberrant brain activity in autism spectrum disorder.

PubMed

Xiang, Jing; Korostenskaja, Milena; Molloy, Cynthia; deGrauw, Xinyao; Leiken, Kimberly; Gilman, Carley; Meinzen-Derr, Jareen; Fujiwara, Hisako; Rose, Douglas F; Mitchell, Terry; Murray, Donna S

2016-01-01

The abnormality of intrinsic brain activity in autism spectrum disorders (ASDs) is still inconclusive. Contradictory results have been found pointing towards hyper-activity or hypo-activity in various brain regions. The present research aims to investigate the spatial and spectral signatures of aberrant brain activity in an unprecedented frequency range of 1-2884 Hz at source levels in ASD using newly developed methods. Seven ASD subjects and age- and gender-matched controls were studied using a high-sampling rate magnetoencephalography (MEG) system. Brain activity in delta (1-4 Hz), theta (4-8 Hz), alpha (8-12 Hz), beta (12-30 Hz), low gamma (30-55 Hz), high gamma (65-90 Hz), ripples (90-200 Hz), high-frequency oscillations (HFOs, 200-1000 Hz), and very high-frequency oscillations (VHFOs, 1000-2884 Hz) was volumetrically localized and measured using wavelet and beamforming. In comparison to controls, ASD subjects had significantly higher odds of alpha activity (8-12 Hz) in the sensorimotor cortex (mu rhythm), and generally high-frequency activity (90-2884 Hz) in the frontal cortex. The source power of HFOs (200-1000 Hz) in the frontal cortex in ASD was significantly elevated as compared with controls. The results suggest that ASD has significantly altered intrinsic brain activity in both low- and high-frequency ranges. Increased intrinsic high-frequency activity in the frontal cortex may play a key role in ASD. Copyright © 2015 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

A Hippocampal Cognitive Prosthesis: Multi-Input, Multi-Output Nonlinear Modeling and VLSI Implementation

PubMed Central

Berger, Theodore W.; Song, Dong; Chan, Rosa H. M.; Marmarelis, Vasilis Z.; LaCoss, Jeff; Wills, Jack; Hampson, Robert E.; Deadwyler, Sam A.; Granacki, John J.

2012-01-01

This paper describes the development of a cognitive prosthesis designed to restore the ability to form new long-term memories typically lost after damage to the hippocampus. The animal model used is delayed nonmatch-to-sample (DNMS) behavior in the rat, and the “core” of the prosthesis is a biomimetic multi-input/multi-output (MIMO) nonlinear model that provides the capability for predicting spatio-temporal spike train output of hippocampus (CA1) based on spatio-temporal spike train inputs recorded presynaptically to CA1 (e.g., CA3). We demonstrate the capability of the MIMO model for highly accurate predictions of CA1 coded memories that can be made on a single-trial basis and in real-time. When hippocampal CA1 function is blocked and long-term memory formation is lost, successful DNMS behavior also is abolished. However, when MIMO model predictions are used to reinstate CA1 memory-related activity by driving spatio-temporal electrical stimulation of hippocampal output to mimic the patterns of activity observed in control conditions, successful DNMS behavior is restored. We also outline the design in very-large-scale integration for a hardware implementation of a 16-input, 16-output MIMO model, along with spike sorting, amplification, and other functions necessary for a total system, when coupled together with electrode arrays to record extracellularly from populations of hippocampal neurons, that can serve as a cognitive prosthesis in behaving animals. PMID:22438335

Componential Network for the Recognition of Tool-Associated Actions: Evidence from Voxel-based Lesion-Symptom Mapping in Acute Stroke Patients.

PubMed

Martin, Markus; Dressing, Andrea; Bormann, Tobias; Schmidt, Charlotte S M; Kümmerer, Dorothee; Beume, Lena; Saur, Dorothee; Mader, Irina; Rijntjes, Michel; Kaller, Christoph P; Weiller, Cornelius

2017-08-01

The study aimed to elucidate areas involved in recognizing tool-associated actions, and to characterize the relationship between recognition and active performance of tool use.We performed voxel-based lesion-symptom mapping in a prospective cohort of 98 acute left-hemisphere ischemic stroke patients (68 male, age mean ± standard deviation, 65 ± 13 years; examination 4.4 ± 2 days post-stroke). In a video-based test, patients distinguished correct tool-related actions from actions with spatio-temporal (incorrect grip, kinematics, or tool orientation) or conceptual errors (incorrect tool-recipient matching, e.g., spreading jam on toast with a paintbrush). Moreover, spatio-temporal and conceptual errors were determined during actual tool use.Deficient spatio-temporal error discrimination followed lesions within a dorsal network in which the inferior parietal lobule (IPL) and the lateral temporal cortex (sLTC) were specifically relevant for assessing functional hand postures and kinematics, respectively. Conversely, impaired recognition of conceptual errors resulted from damage to ventral stream regions including anterior temporal lobe. Furthermore, LTC and IPL lesions impacted differently on action recognition and active tool use, respectively.In summary, recognition of tool-associated actions relies on a componential network. Our study particularly highlights the dissociable roles of LTC and IPL for the recognition of action kinematics and functional hand postures, respectively. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Mining patterns in persistent surveillance systems with smart query and visual analytics

NASA Astrophysics Data System (ADS)

Habibi, Mohammad S.; Shirkhodaie, Amir

2013-05-01

In Persistent Surveillance Systems (PSS) the ability to detect and characterize events geospatially help take pre-emptive steps to counter adversary's actions. Interactive Visual Analytic (VA) model offers this platform for pattern investigation and reasoning to comprehend and/or predict such occurrences. The need for identifying and offsetting these threats requires collecting information from diverse sources, which brings with it increasingly abstract data. These abstract semantic data have a degree of inherent uncertainty and imprecision, and require a method for their filtration before being processed further. In this paper, we have introduced an approach based on Vector Space Modeling (VSM) technique for classification of spatiotemporal sequential patterns of group activities. The feature vectors consist of an array of attributes extracted from generated sensors semantic annotated messages. To facilitate proper similarity matching and detection of time-varying spatiotemporal patterns, a Temporal-Dynamic Time Warping (DTW) method with Gaussian Mixture Model (GMM) for Expectation Maximization (EM) is introduced. DTW is intended for detection of event patterns from neighborhood-proximity semantic frames derived from established ontology. GMM with EM, on the other hand, is employed as a Bayesian probabilistic model to estimated probability of events associated with a detected spatiotemporal pattern. In this paper, we present a new visual analytic tool for testing and evaluation group activities detected under this control scheme. Experimental results demonstrate the effectiveness of proposed approach for discovery and matching of subsequences within sequentially generated patterns space of our experiments.

Following the ontogeny of retinal waves: pan-retinal recordings of population dynamics in the neonatal mouse

PubMed Central

Maccione, Alessandro; Hennig, Matthias H; Gandolfo, Mauro; Muthmann, Oliver; van Coppenhagen, James; Eglen, Stephen J; Berdondini, Luca; Sernagor, Evelyne

2014-01-01

The immature retina generates spontaneous waves of spiking activity that sweep across the ganglion cell layer during a limited period of development before the onset of visual experience. The spatiotemporal patterns encoded in the waves are believed to be instructive for the wiring of functional connections throughout the visual system. However, the ontogeny of retinal waves is still poorly documented as a result of the relatively low resolution of conventional recording techniques. Here, we characterize the spatiotemporal features of mouse retinal waves from birth until eye opening in unprecedented detail using a large-scale, dense, 4096-channel multielectrode array that allowed us to record from the entire neonatal retina at near cellular resolution. We found that early cholinergic waves propagate with random trajectories over large areas with low ganglion cell recruitment. They become slower, smaller and denser when GABAA signalling matures, as occurs beyond postnatal day (P) 7. Glutamatergic influences dominate from P10, coinciding with profound changes in activity dynamics. At this time, waves cease to be random and begin to show repetitive trajectories confined to a few localized hotspots. These hotspots gradually tile the retina with time, and disappear after eye opening. Our observations demonstrate that retinal waves undergo major spatiotemporal changes during ontogeny. Our results support the hypotheses that cholinergic waves guide the refinement of retinal targets and that glutamatergic waves may also support the wiring of retinal receptive fields. PMID:24366261

Capture of activation during ventricular arrhythmia using distributed stimulation.

PubMed

Meunier, Jason M; Ramalingam, Sanjiv; Lin, Shien-Fong; Patwardhan, Abhijit R

2007-04-01

Results of previous studies suggest that pacing strength stimuli can capture activation during ventricular arrhythmia locally near pacing sites. The existence of spatio-temporal distribution of excitable gap during arrhythmia suggests that multiple and timed stimuli delivered over a region may permit capture over larger areas. Our objective in this study was to evaluate the efficacy of using spatially distributed pacing (DP) to capture activation during ventricular arrhythmia. Data were obtained from rabbit hearts which were placed against a lattice of parallel wires through which biphasic pacing stimuli were delivered. Electrical activity was recorded optically. Pacing stimuli were delivered in sequence through the parallel wires starting with the wire closest to the apex and ending with one closest to the base. Inter-stimulus delay was based on conduction velocity. Time-frequency analysis of optical signals was used to determine variability in activation. A decrease in standard deviation of dominant frequencies of activation from a grid of locations that spanned the captured area and a concurrence with paced frequency were used as an index of capture. Results from five animals showed that the average standard deviation decreased from 0.81 Hz during arrhythmia to 0.66 Hz during DP at pacing cycle length of 125 ms (p = 0.03) reflecting decreased spatio-temporal variability in activation during DP. Results of time-frequency analysis during these pacing trials showed agreement between activation and paced frequencies. These results show that spatially distributed and timed stimulation can be used to modify and capture activation during ventricular arrhythmia.

Exposure to subliminal arousing stimuli induces robust activation in the amygdala, hippocampus, anterior cingulate, insular cortex and primary visual cortex: a systematic meta-analysis of fMRI studies.

PubMed

Brooks, S J; Savov, V; Allzén, E; Benedict, C; Fredriksson, R; Schiöth, H B

2012-02-01

Functional Magnetic Resonance Imaging (fMRI) demonstrates that the subliminal presentation of arousing stimuli can activate subcortical brain regions independently of consciousness-generating top-down cortical modulation loops. Delineating these processes may elucidate mechanisms for arousal, aberration in which may underlie some psychiatric conditions. Here we are the first to review and discuss four Activation Likelihood Estimation (ALE) meta-analyses of fMRI studies using subliminal paradigms. We find a maximum of 9 out of 12 studies using subliminal presentation of faces contributing to activation of the amygdala, and also a significantly high number of studies reporting activation in the bilateral anterior cingulate, bilateral insular cortex, hippocampus and primary visual cortex. Subliminal faces are the strongest modality, whereas lexical stimuli are the weakest. Meta-analyses independent of studies using Regions of Interest (ROI) revealed no biasing effect. Core neuronal arousal in the brain, which may be at first independent of conscious processing, potentially involves a network incorporating primary visual areas, somatosensory, implicit memory and conflict monitoring regions. These data could provide candidate brain regions for the study of psychiatric disorders associated with aberrant automatic emotional processing. Copyright © 2011 Elsevier Inc. All rights reserved.

Aberrant AKT activation drives well-differentiated liposarcoma

PubMed Central

Gutierrez, Alejandro; Snyder, Eric L.; Marino-Enriquez, Adrian; Zhang, Yi-Xiang; Sioletic, Stefano; Kozakewich, Elena; Grebliunaite, Ruta; Ou, Wen-bin; Sicinska, Ewa; Raut, Chandrajit P.; Demetri, George D.; Perez-Atayde, Antonio R.; Wagner, Andrew J.; Fletcher, Jonathan A.; Fletcher, Christopher D. M.; Look, A. Thomas

2011-01-01

Well-differentiated liposarcoma (WDLPS), one of the most common human sarcomas, is poorly responsive to radiation and chemotherapy, and the lack of animal models suitable for experimental analysis has seriously impeded functional investigation of its pathobiology and development of effective targeted therapies. Here, we show that zebrafish expressing constitutively active Akt2 in mesenchymal progenitors develop WDLPS that closely resembles the human disease. Tumor incidence rates were 8% in p53 wild-type zebrafish, 6% in p53 heterozygotes, and 29% in p53-homozygous mutant zebrafish (P = 0.013), indicating that aberrant Akt activation collaborates with p53 mutation in WDLPS pathogenesis. Analysis of primary clinical specimens of WDLPS, and of the closely related dedifferentiated liposarcoma (DDLPS) subtype, revealed immunohistochemical evidence of AKT activation in 27% of cases. Western blot analysis of a panel of cell lines derived from patients with WDLPS or DDLPS revealed robust AKT phosphorylation in all cell lines examined, even when these cells were cultured in serum-free media. Moreover, BEZ235, a small molecule inhibitor of PI3K and mammalian target of rapamycin that effectively inhibits AKT activation in these cells, impaired viability at nanomolar concentrations. Our findings are unique in providing an animal model to decipher the molecular pathogenesis of WDLPS, and implicate AKT as a previously unexplored therapeutic target in this chemoresistant sarcoma. PMID:21930930