Sequentially Programmable and Cellularly Selective Assembly of Fluorescent Polymerized Vesicles for Monitoring Cell Apoptosis.

PubMed

Peng, Shu; Pan, Yu-Chen; Wang, Yaling; Xu, Zhe; Chen, Chao; Ding, Dan; Wang, Yongjian; Guo, Dong-Sheng

2017-11-01

The introduction of controlled self-assembly into living organisms opens up desired biomedical applications in wide areas including bioimaging/assays, drug delivery, and tissue engineering. Besides the enzyme-activated examples reported before, controlled self-assembly under integrated stimuli, especially in the form of sequential input, is unprecedented and ultimately challenging. This study reports a programmable self-assembling strategy in living cells under sequentially integrated control of both endogenous and exogenous stimuli. Fluorescent polymerized vesicles are constructed by using cholinesterase conversion followed by photopolymerization and thermochromism. Furthermore, as a proof-of-principle application, the cell apoptosis involved in the overexpression of cholinesterase in virtue of the generated fluorescence is monitored, showing potential in screening apoptosis-inducing drugs. The approach exhibits multiple advantages for bioimaging in living cells, including specificity to cholinesterase, red emission, wash free, high signal-to-noise ratio.

Sequential Dependencies in Categorical Judgments of Radiographic Images

ERIC Educational Resources Information Center

Beckstead, Jason W.; Boutis, Kathy; Pecaric, Martin; Pusic, Martin V.

2017-01-01

Sequential context effects, the psychological interactions occurring between the events of successive trials when a sequence of similar stimuli are judged, have interested psychologists for decades. It has been well established that individuals exhibit sequential context effects in psychophysical experiments involving unidimensional stimuli.…

Immunoreceptor Tyrosine-based Inhibitory Motif (ITIM)-mediated Inhibitory Signaling is Regulated by Sequential Phosphorylation Mediated by Distinct Nonreceptor Tyrosine Kinases: A Case Study Involving PECAM-1

PubMed Central

Tourdot, Benjamin E.; Brenner, Michelle K.; Keough, Kathleen C.; Holyst, Trudy; Newman, Peter J.; Newman, Debra K.

2013-01-01

The activation state of many blood and vascular cells is tightly controlled by a delicate balance between receptors that contain immunoreceptor tyrosine-based activation motifs (ITAMs) and those that contain immunoreceptor tyrosine-based inhibitory motifs (ITIMs). Precisely how the timing of cellular activation by ITAM-coupled receptors is regulated by ITIM-containing receptors is, however, poorly understood. Using platelet endothelial cell adhesion molecule 1 (PECAM-1) as a prototypical ITIM-bearing receptor, we demonstrate that initiation of inhibitory signaling occurs via a novel, sequential process in which Src family kinases phosphorylate the C-terminal ITIM, thereby enabling phosphorylation of the N-terminal ITIM of PECAM-1 by other Src homology 2 domain-containing non-receptor tyrosine kinases (NRTKs). NRTKs capable of mediating the second phosphorylation event include C-terminal Src kinase (Csk) and Bruton’s tyrosine kinase (Btk). Btk and Csk function downstream of phosphatidylinositol 3-kinase (PI3K) activation during ITAM-dependent platelet activation. In ITAM-activated platelets that were treated with a PI3K inhibitor, PECAM-1 was phosphorylated but did not bind the tandem SH2 domain-containing tyrosine phosphatase SHP-2, indicating that it was not phosphorylated on its N-terminal ITIM. Csk bound to and phosphorylated PECAM-1 more efficiently than did Btk, and required its SH2 domain to perform these functions. Additionally, the phosphorylation of the N-terminal ITIM of Siglec-9 by Csk is enhanced by the prior phosphorylation of its C-terminal ITIM, providing evidence that the ITIMs of other dual ITIM-containing receptors are also sequentially phosphorylated. On the basis of these findings, we propose that sequential ITIM phosphorylation provides a general mechanism for precise temporal control over the recruitment and activation of tandem SH2 domain-containing tyrosine phosphatases that dampen ITAM-dependent signals. PMID:23418871

Human IgG2- and IgG4-expressing memory B cells display enhanced molecular and phenotypic signs of maturity and accumulate with age.

PubMed

de Jong, Britt G; IJspeert, Hanna; Marques, Lemelinda; van der Burg, Mirjam; van Dongen, Jacques Jm; Loos, Bruno G; van Zelm, Menno C

2017-10-01

The mechanisms involved in sequential immunoglobulin G (IgG) class switching are still largely unknown. Sequential IG class switching is linked to higher levels of somatic hypermutation (SHM) in vivo, but it remains unclear if these are generated temporally during an immune response or upon activation in a secondary response. We here aimed to uncouple these processes and to distinguish memory B cells from primary and secondary immune responses. SHM levels and IgG subclasses were studied with 454 pyrosequencing on blood mononuclear cells from young children and adults as models for primary and secondary immunological memory. Additional sequencing and detailed immunophenotyping with IgG subclass-specific antibodies was performed on purified IgG + memory B-cell subsets. In both children and adults, SHM levels were higher in transcripts involving more downstream-located IGHG genes (esp. IGHG2 and IGHG4). In adults, SHM levels were significantly higher than in children, and downstream IGHG genes were more frequently utilized. This was associated with increased frequencies of CD27 + IgG + memory B cells, which contained higher levels of SHM, more IGHG2 usage, and higher expression levels of activation markers than CD27 - IgG + memory B cells. We conclude that secondary immunological memory accumulates with age and these memory B cells express CD27, high levels of activation markers, and carry high SHM levels and frequent usage of IGHG2. These new insights contribute to our understanding of sequential IgG subclass switching and show a potential relevance of using serum IgG2 levels or numbers of IgG2-expressing B cells as markers for efficient generation of memory responses.

Gold-catalyzed sequential annulations towards 3,4-fused bi/tri-cyclic furans involving a [3+2+2]-cycloaddition.

PubMed

Liu, Suna; Yang, Pu; Peng, Shiyong; Zhu, Chenghao; Cao, Shengyu; Li, Jian; Sun, Jiangtao

2017-01-17

A gold-catalyzed sequential annulation reaction to prepare 3,4-fused bicyclic furan compounds has been realized by employing 2-(1-alkynyl)-2-alken-1-ones and 1,3,5-triazines as the starting materials under mild reaction conditions. This protocol features multiple bond formation in a single operation with the incorporation of two nitrogen and two carbon atoms into the final products. A mechanistic investigation reveals that the sequential annulations involved an unprecedented stepwise [3+2+2]-cycloaddition.

Sequential expression of cyclooxygenase-2, glutamate receptor-2, and platelet activating factor receptor in rat hippocampal neurons after fluid percussion injury

PubMed Central

Li, Zhiqiang; Shu, Qingming; Li, Lingzhi; Ge, Maolin; Zhang, Yongliang

2014-01-01

Traumatic brain injury causes gene expression changes in different brain regions. Occurrence and development of traumatic brain injury are closely related, involving expression of three factors, namely cyclooxygenase-2, glutamate receptor-2, and platelet activating factor receptor. However, little is known about the correlation of these three factors and brain neuronal injury. In this study, primary cultured rat hippocampal neurons were subjected to fluid percussion injury according to Scott's method, with some modifications. RT-PCR and semi-quantitative immunocytochemical staining was used to measure the expression levels of cyclooxygenase-2, glutamate receptor-2, and platelet activating factor receptor. Our results found that cyclooxygenase-2 expression were firstly increased post-injury, and then decreased. Both mRNA and protein expression levels reached peaks at 8 and 12 hours post-injury, respectively. Similar sequential changes in glutamate receptor 2 were observed, with highest levels mRNA and protein expression at 8 and 12 hours post-injury respectively. On the contrary, the expressions of platelet activating factor receptor were firstly decreased post-injury, and then increased. Both mRNA and protein expression levels reached the lowest levels at 8 and 12 hours post-injury, respectively. Totally, our findings suggest that these three factors are involved in occurrence and development of hippocampal neuronal injury. PMID:25206921

A Bayesian Theory of Sequential Causal Learning and Abstract Transfer.

PubMed

Lu, Hongjing; Rojas, Randall R; Beckers, Tom; Yuille, Alan L

2016-03-01

Two key research issues in the field of causal learning are how people acquire causal knowledge when observing data that are presented sequentially, and the level of abstraction at which learning takes place. Does sequential causal learning solely involve the acquisition of specific cause-effect links, or do learners also acquire knowledge about abstract causal constraints? Recent empirical studies have revealed that experience with one set of causal cues can dramatically alter subsequent learning and performance with entirely different cues, suggesting that learning involves abstract transfer, and such transfer effects involve sequential presentation of distinct sets of causal cues. It has been demonstrated that pre-training (or even post-training) can modulate classic causal learning phenomena such as forward and backward blocking. To account for these effects, we propose a Bayesian theory of sequential causal learning. The theory assumes that humans are able to consider and use several alternative causal generative models, each instantiating a different causal integration rule. Model selection is used to decide which integration rule to use in a given learning environment in order to infer causal knowledge from sequential data. Detailed computer simulations demonstrate that humans rely on the abstract characteristics of outcome variables (e.g., binary vs. continuous) to select a causal integration rule, which in turn alters causal learning in a variety of blocking and overshadowing paradigms. When the nature of the outcome variable is ambiguous, humans select the model that yields the best fit with the recent environment, and then apply it to subsequent learning tasks. Based on sequential patterns of cue-outcome co-occurrence, the theory can account for a range of phenomena in sequential causal learning, including various blocking effects, primacy effects in some experimental conditions, and apparently abstract transfer of causal knowledge. Copyright © 2015 Cognitive Science Society, Inc.

Sequential vs. simultaneous photokilling by mitochondrial and lysosomal photodamage

NASA Astrophysics Data System (ADS)

Kessel, David

2017-02-01

We previously reported that a low level of lysosomal photoda mage can markedly promote the subsequent efficacy of PDT directed at mitochondria. This involves release of Ca2+ from photo damaged lysosomes, cleavage of the autophagy-associated protein ATG5 after activation of calpain and an interaction between the ATG5 fragment and mitochondria resulting in enhanced apoptosis. Inhibition of calpain activity abolished th is effect. We examined permissible irradiation sequences. Lysosomal photodamage must occur first with the `enhancement' effect showing a short half-life ( 15 min), presumably reflecting the survival of the ATG5 fragment. Simultaneous photo damage to both loci was found to be as effective as the sequential protocol. Since Photofrin can target both lysosomes and mitochondria for photo damage, this broad spectrum of photo damage may explain the efficacy of this photo sensitizing agent in spite of a sub-optimal absorbance profile at a sub- optimal wavelength for tissue transparency.

What Difference Does Art Make in Science? A Comparative Study of Meaning-Making at Elementary School

ERIC Educational Resources Information Center

Jakobson, Britt; Wickman, Per-Olof

2015-01-01

Here we examine the role art activities play in aesthetic experience and learning of science. We compare recordings of two sequential occurrences in an elementary school class. The purpose of the first sequence was scientific and involved the children in observing leaves with magnifiers. The second sequence had an artistic purpose, where the…

A Bayesian Theory of Sequential Causal Learning and Abstract Transfer

ERIC Educational Resources Information Center

Lu, Hongjing; Rojas, Randall R.; Beckers, Tom; Yuille, Alan L.

2016-01-01

Two key research issues in the field of causal learning are how people acquire causal knowledge when observing data that are presented sequentially, and the level of abstraction at which learning takes place. Does sequential causal learning solely involve the acquisition of specific cause-effect links, or do learners also acquire knowledge about…

Sequential events in the irreversible thermal denaturation of human brain-type creatine kinase by spectroscopic methods.

PubMed

Gao, Yan-Song; Su, Jing-Tan; Yan, Yong-Bin

2010-06-25

The non-cooperative or sequential events which occur during protein thermal denaturation are closely correlated with protein folding, stability, and physiological functions. In this research, the sequential events of human brain-type creatine kinase (hBBCK) thermal denaturation were studied by differential scanning calorimetry (DSC), CD, and intrinsic fluorescence spectroscopy. DSC experiments revealed that the thermal denaturation of hBBCK was calorimetrically irreversible. The existence of several endothermic peaks suggested that the denaturation involved stepwise conformational changes, which were further verified by the discrepancy in the transition curves obtained from various spectroscopic probes. During heating, the disruption of the active site structure occurred prior to the secondary and tertiary structural changes. The thermal unfolding and aggregation of hBBCK was found to occur through sequential events. This is quite different from that of muscle-type CK (MMCK). The results herein suggest that BBCK and MMCK undergo quite dissimilar thermal unfolding pathways, although they are highly conserved in the primary and tertiary structures. A minor difference in structure might endow the isoenzymes dissimilar local stabilities in structure, which further contribute to isoenzyme-specific thermal stabilities.

Detection, mapping and estimation of rate of spread of grass fires from southern African ERTS-1 imagery

NASA Technical Reports Server (NTRS)

Wightman, J. M.

1973-01-01

Sequential band-6 imagery of the Zambesi Basin of southern Africa recorded substantial changes in burn patterns resulting from late dry season grass fires. One example from northern Botswana, indicates that a fire consumed approximately 70 square miles of grassland over a 24-hour period. Another example from western Zambia indicates increased fire activity over a 19-day period. Other examples clearly define the area of widespread grass fires in Angola, Botswana, Rhodesia and Zambia. From the fire patterns visible on the sequential portions of the imagery, and the time intervals involved, the rates of spread of the fires are estimated and compared with estimates derived from experimental burning plots in Zambia and Canada. It is concluded that sequential ERTS-1 imagery, of the quality studied, clearly provides the information needed to detect and map grass fires and to monitor their rates of spread in this region during the late dry season.

Effects of Training Auditory Sequential Memory and Attention on Reading.

ERIC Educational Resources Information Center

Klein, Pnina S.; Schwartz, Allen A.

To determine if auditory sequential memory (ASM) in young children can be improved through training and to discover the effects of such training on the reading scores of children with reading problems, a study was conducted involving 92 second and third graders. For purposes of this study, auditory sequential memory was defined as the ability to…

Coding Manual for Subject/Peer/Teacher Sequential Interactions in Academic Survival Skill Settings. Report No. 4.

ERIC Educational Resources Information Center

Cobb, Joseph A.; Hops, Hyman

The manual of classroom observation techniques is intended to provide observers with detailed descriptions of standardized procedures and techniques involved in sequential data collection in a classroom. Focus is on obtaining reliable data on sequential interactions between teachers, peers, and subjects (each of the students in turn is a subject).…

Synchronization and coordination of sequences in two neural ensembles

NASA Astrophysics Data System (ADS)

Venaille, Antoine; Varona, Pablo; Rabinovich, Mikhail I.

2005-06-01

There are many types of neural networks involved in the sequential motor behavior of animals. For high species, the control and coordination of the network dynamics is a function of the higher levels of the central nervous system, in particular the cerebellum. However, in many cases, especially for invertebrates, such coordination is the result of direct synaptic connections between small circuits. We show here that even the chaotic sequential activity of small model networks can be coordinated by electrotonic synapses connecting one or several pairs of neurons that belong to two different networks. As an example, we analyzed the coordination and synchronization of the sequential activity of two statocyst model networks of the marine mollusk Clione. The statocysts are gravity sensory organs that play a key role in postural control of the animal and the generation of a complex hunting motor program. Each statocyst network was modeled by a small ensemble of neurons with Lotka-Volterra type dynamics and nonsymmetric inhibitory interactions. We studied how two such networks were synchronized by electrical coupling in the presence of an external signal which lead to winnerless competition among the neurons. We found that as a function of the number and the strength of connections between the two networks, it is possible to coordinate and synchronize the sequences that each network generates with its own chaotic dynamics. In spite of the chaoticity, the coordination of the signals is established through an activation sequence lock for those neurons that are active at a particular instant of time.

Neural mechanisms of peristalsis in the isolated rabbit distal colon: a neuromechanical loop hypothesis.

PubMed

Dinning, Phil G; Wiklendt, Lukasz; Omari, Taher; Arkwright, John W; Spencer, Nick J; Brookes, Simon J H; Costa, Marcello

2014-01-01

Propulsive contractions of circular muscle are largely responsible for the movements of content along the digestive tract. Mechanical and electrophysiological recordings of isolated colonic circular muscle have demonstrated that localized distension activates ascending and descending interneuronal pathways, evoking contraction orally and relaxation anally. These polarized enteric reflex pathways can theoretically be sequentially activated by the mechanical stimulation of the advancing contents. Here, we test the hypothesis that initiation and propagation of peristaltic contractions involves a neuromechanical loop; that is an initial gut distension activates local and oral reflex contraction and anal reflex relaxation, the subsequent movement of content then acts as new mechanical stimulus triggering sequentially reflex contractions/relaxations at each point of the gut resulting in a propulsive peristaltic contraction. In fluid filled isolated rabbit distal colon, we combined spatiotemporal mapping of gut diameter and intraluminal pressure with a new analytical method, allowing us to identify when and where active (neurally-driven) contraction or relaxation occurs. Our data indicate that gut dilation is associated with propagating peristaltic contractions, and that the associated level of dilation is greater than that preceding non-propagating contractions (2.7 ± 1.4 mm vs. 1.6 ± 1.2 mm; P < 0.0001). These propagating contractions lead to the formation of boluses that are propelled by oral active neurally driven contractions. The propelled boluses also activate neurally driven anal relaxations, in a diameter dependent manner. These data support the hypothesis that neural peristalsis is the consequence of the activation of a functional loop involving mechanical dilation which activates polarized enteric circuits. These produce propulsion of the bolus which activates further anally, polarized enteric circuits by distension, thus closing the neuromechanical loop.

Reading Different Orthographies: An fMRI Study of Phrase Reading in Hindi-English Bilinguals

ERIC Educational Resources Information Center

Kumar, Uttam; Das, Tanusree; Bapi, Raju S.; Padakannaya, Prakash; Joshi, R. Malatesha; Singh, Nandini C.

2010-01-01

The aim of the present study was to use functional imaging to compare cortical activations involved in reading Hindi and English that differ markedly in terms of their orthographies by a group of late bilinguals, more fluent in Hindi (L1) than English (L2). English is alphabetic and linear, in that vowels and consonants are arranged sequentially.…

C-quence: a tool for analyzing qualitative sequential data.

PubMed

Duncan, Starkey; Collier, Nicholson T

2002-02-01

C-quence is a software application that matches sequential patterns of qualitative data specified by the user and calculates the rate of occurrence of these patterns in a data set. Although it was designed to facilitate analyses of face-to-face interaction, it is applicable to any data set involving categorical data and sequential information. C-quence queries are constructed using a graphical user interface. The program does not limit the complexity of the sequential patterns specified by the user.

Cortical responses following simultaneous and sequential retinal neurostimulation with different return configurations.

PubMed

Barriga-Rivera, Alejandro; Morley, John W; Lovell, Nigel H; Suaning, Gregg J

2016-08-01

Researchers continue to develop visual prostheses towards safer and more efficacious systems. However limitations still exist in the number of stimulating channels that can be integrated. Therefore there is a need for spatial and time multiplexing techniques to provide improved performance of the current technology. In particular, bright and high-contrast visual scenes may require simultaneous activation of several electrodes. In this research, a 24-electrode array was suprachoroidally implanted in three normally-sighted cats. Multi-unit activity was recorded from the primary visual cortex. Four stimulation strategies were contrasted to provide activation of seven electrodes arranged hexagonally: simultaneous monopolar, sequential monopolar, sequential bipolar and hexapolar. Both monopolar configurations showed similar cortical activation maps. Hexapolar and sequential bipolar configurations activated a lower number of cortical channels. Overall, the return configuration played a more relevant role in cortical activation than time multiplexing and thus, rapid sequential stimulation may assist in reducing the number of channels required to activate large retinal areas.

Characteristics of sequential targeting of brain glioma for transferrin-modified cisplatin liposome.

PubMed

Lv, Qing; Li, Li-Min; Han, Min; Tang, Xin-Jiang; Yao, Jin-Na; Ying, Xiao-Ying; Li, Fan-Zhu; Gao, Jian-Qing

2013-02-28

Methods on how to improve the sequential targeting of glioma subsequent to passing of drug through the blood-brain barrier (BBB) have been occasionally reported. However, the characteristics involved are poorly understood. In the present study, cisplatin (Cis) liposome (lipo) was modified with transferrin (Tf) to investigate the characteristics of potential sequential targeting to glioma. In bEnd3/C6 co-culture BBB models, higher transport efficiency across the BBB and cytotoxicity in basal C6 cells induced by Cis-lipo(Tf) than Cis-lipo and Cis-solution, suggest its sequential targeting effect. Interestingly, similar liposomal morphology as that of donor compartment was first demonstrated in the receptor solution of BBB models. Meanwhile, a greater acquisition in the lysosome of bEnd3, distributed sequentially into the nucleus of C6 cells were found for the Cis-lipo(Tf). Pre-incubation of chlorpromazine and Tf inhibited this process, indicating that a clathrin-dependent endocytosis is involved in the transport of Cis-lipo(Tf) across the BBB. Copyright © 2013 Elsevier B.V. All rights reserved.

Reaction pathways involved in CH4 conversion on Pd/Al2O3 catalysts : TAP as a powerful tool for the elucidation of the effective role of the metal/support interface

NASA Astrophysics Data System (ADS)

Granger, Pascal

2016-02-01

Temporal Analysis of Products (TAP) reactor offers an alternative to draw direct structure/activity relationships checked on Natural Gas-fuelled Vehicle (NGV) catalysts Determination of accurate kinetic constants for methane adsorption from single pulse experiments and subsequent investigation of sequential surface reactions from alternative CH4/O2 pulse experiments provides a straightforward visualization of the involvement of the metal/support interface on freshly-prepared catalysts and the loss of this effect on aged single palladium based catalysts.

Robustness of the sequential lineup advantage.

PubMed

Gronlund, Scott D; Carlson, Curt A; Dailey, Sarah B; Goodsell, Charles A

2009-06-01

A growing movement in the United States and around the world involves promoting the advantages of conducting an eyewitness lineup in a sequential manner. We conducted a large study (N = 2,529) that included 24 comparisons of sequential versus simultaneous lineups. A liberal statistical criterion revealed only 2 significant sequential lineup advantages and 3 significant simultaneous advantages. Both sequential advantages occurred when the good photograph of the guilty suspect or either innocent suspect was in the fifth position in the sequential lineup; all 3 simultaneous advantages occurred when the poorer quality photograph of the guilty suspect or either innocent suspect was in the second position. Adjusting the statistical criterion to control for the multiple tests (.05/24) revealed no significant sequential advantages. Moreover, despite finding more conservative overall choosing for the sequential lineup, no support was found for the proposal that a sequential advantage was due to that conservative criterion shift. Unless lineups with particular characteristics predominate in the real world, there appears to be no strong preference for conducting lineups in either a sequential or a simultaneous manner. (PsycINFO Database Record (c) 2009 APA, all rights reserved).

Inertial navigation sensor integrated obstacle detection system

NASA Technical Reports Server (NTRS)

Bhanu, Bir (Inventor); Roberts, Barry A. (Inventor)

1992-01-01

A system that incorporates inertial sensor information into optical flow computations to detect obstacles and to provide alternative navigational paths free from obstacles. The system is a maximally passive obstacle detection system that makes selective use of an active sensor. The active detection typically utilizes a laser. Passive sensor suite includes binocular stereo, motion stereo and variable fields-of-view. Optical flow computations involve extraction, derotation and matching of interest points from sequential frames of imagery, for range interpolation of the sensed scene, which in turn provides obstacle information for purposes of safe navigation.

Fatigue reduction during aggregated and distributed sequential stimulation.

PubMed

Bergquist, Austin J; Babbar, Vishvek; Ali, Saima; Popovic, Milos R; Masani, Kei

2017-08-01

Transcutaneous neuromuscular electrical stimulation (NMES) can generate muscle contractions for rehabilitation and exercise. However, NMES-evoked contractions are limited by fatigue when they are delivered "conventionally" (CONV) using a single active electrode. Researchers have developed "sequential" (SEQ) stimulation, involving rotation of pulses between multiple "aggregated" (AGGR-SEQ) or "distributed" (DISTR-SEQ) active electrodes, to reduce fatigue (torque-decline) by reducing motor unit discharge rates. The primary objective was to compare fatigue-related outcomes, "potentiation," "variability," and "efficiency" between CONV, AGGR-SEQ, and DISTR-SEQ stimulation of knee extensors in healthy participants. Torque and current were recorded during testing with fatiguing trains using each NMES type under isometric and isokinetic (180°/s) conditions. Compared with CONV stimulation, SEQ techniques reduced fatigue-related outcomes, increased potentiation, did not affect variability, and reduced efficiency. SEQ techniques hold promise for reducing fatigue during NMES-based rehabilitation and exercise; however, optimization is required to improve efficiency. Muscle Nerve 56: 271-281, 2017. © 2016 Wiley Periodicals, Inc.

Hierarchical nonlinear dynamics of human attention.

PubMed

Rabinovich, Mikhail I; Tristan, Irma; Varona, Pablo

2015-08-01

Attention is the process of focusing mental resources on a specific cognitive/behavioral task. Such brain dynamics involves different partially overlapping brain functional networks whose interconnections change in time according to the performance stage, and can be stimulus-driven or induced by an intrinsically generated goal. The corresponding activity can be described by different families of spatiotemporal discrete patterns or sequential dynamic modes. Since mental resources are finite, attention modalities compete with each other at all levels of the hierarchy, from perception to decision making and behavior. Cognitive activity is a dynamical process and attention possesses some universal dynamical characteristics. Thus, it is time to apply nonlinear dynamical theory for the description and prediction of hierarchical attentional tasks. Such theory has to include the analyses of attentional control stability, the time cost of attention switching, the finite capacity of informational resources in the brain, and the normal and pathological bifurcations of attention sequential dynamics. In this paper we have integrated today's knowledge, models and results in these directions. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effects of Training Auditory Sequential Memory and Attention on Reading.

ERIC Educational Resources Information Center

Klein, Pnina S.; Schwartz, Allen A.

1979-01-01

The study, involving 92 second and third graders with deficits in reading and auditory sequential memory (ASM), examined the possibility of improving ASM through training and the relationship between this training and reading ability. (Author/CL)

Sequential CD4-Coreceptor Interactions in Human Immunodeficiency Virus Type 1 Env Function: Soluble CD4 Activates Env for Coreceptor-Dependent Fusion and Reveals Blocking Activities of Antibodies against Cryptic Conserved Epitopes on gp120

PubMed Central

Salzwedel, Karl; Smith, Erica D.; Dey, Barna; Berger, Edward A.

2000-01-01

We devised an experimental system to examine sequential events by which the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) interacts with CD4 and coreceptor to induce membrane fusion. Recombinant soluble CD4 (sCD4) activated fusion between effector cells expressing Env and target cells expressing coreceptor (CCR5 or CXCR4) but lacking CD4. sCD4-activated fusion was dose dependent, occurred comparably with two- and four-domain proteins, and demonstrated Env-coreceptor specificities parallel to those reported in conventional fusion and infectivity systems. Fusion activation occurred upon sCD4 preincubation and washing of the Env-expressing effector cells but not the coreceptor-bearing target cells, thereby demonstrating that sCD4 exerts its effects by acting on Env. These findings provide direct functional evidence for a sequential two-step model of Env-receptor interactions, whereby gp120 binds first to CD4 and becomes activated for subsequent functional interaction with coreceptor, leading to membrane fusion. We used the sCD4-activated system to explore neutralization by the anti-gp120 human monoclonal antibodies 17b and 48d. These antibodies reportedly bind conserved CD4-induced epitopes involved in coreceptor interactions but neutralize HIV-1 infection only weakly. We found that 17b and 48d had minimal effects in the standard cell fusion system using target cells expressing both CD4 and coreceptor but potently blocked sCD4-activated fusion with target cells expressing coreceptor alone. Both antibodies strongly inhibited sCD4-activated fusion by Envs from genetically diverse HIV-1 isolates. Thus, the sCD4-activated system reveals conserved Env-blocking epitopes that are masked in native Env and hence not readily detected by conventional systems. PMID:10590121

Computer-Based Instruction for TRIDENT FBM Training

DTIC Science & Technology

1976-06-01

remote voice feedback to an operator. In this case it is possible to display text which represents the voice messages required during sequential ...provides two main services: (a) the preparation of missiles for sequential launching with self-guidance after launch, and (b) the coordination of...monitor- ing the status of the guidance system in each missile. FCS SWS coordina- tion consists of monitoring systems involved in sequential functions at

Executive function skills and academic achievement gains in prekindergarten: Contributions of learning-related behaviors.

PubMed

Nesbitt, Kimberly Turner; Farran, Dale Clark; Fuhs, Mary Wagner

2015-07-01

Although research suggests associations between children's executive function skills and their academic achievement, the specific mechanisms that may help explain these associations in early childhood are unclear. This study examined whether children's (N = 1,103; M age = 54.5 months) executive function skills at the beginning of prekindergarten (pre-K) predict their learning-related behaviors in the classroom and whether these behaviors then mediate associations between children's executive function skills and their pre-K literacy, language, and mathematic gains. Learning-related behaviors were quantified in terms of (a) higher levels of involvement in learning opportunities; (b) greater frequency of participation in activities that require sequential steps; (c) more participation in social-learning interactions; and (d) less instances of being unoccupied, disruptive, or in time out. Results indicated that children's learning-related behaviors mediated associations between executive function skills and literacy and mathematics gains through children's level of involvement, sequential learning behaviors, and disengagement from the classroom. The implications of the findings for early childhood education are discussed. (c) 2015 APA, all rights reserved).

Ponto-medullary nuclei involved in the generation of sequential pharyngeal swallowing and concomitant protective laryngeal adduction in situ

PubMed Central

Bautista, Tara G; Dutschmann, Mathias

2014-01-01

Both swallowing and respiration involve postinspiratory laryngeal adduction. Swallowing-related postinspiratory neurons are likely to be located in the nucleus of the solitary tract (NTS) and those involved in respiration are found in the Kölliker–Fuse nucleus (KF). The function of KF and NTS in the generation of swallowing and its coordination with respiration was investigated in perfused brainstem preparations of juvenile rats (n = 41). Orally injected water evoked sequential pharyngeal swallowing (s-PSW) seen as phasic, spindle-shaped bursting of vagal nerve activity (VNA) against tonic postinspiratory discharge. KF inhibition by microinjecting isoguvacine (GABAA receptor agonist) selectively attenuated tonic postinspiratory VNA (n = 10, P < 0.001) but had no effect on frequency or timing of s-PSW. KF disinhibition after bicuculline (GABAA receptor antagonist) microinjections caused an increase of the tonic VNA (n = 8, P < 0.01) resulting in obscured and delayed phasic s-PSW. Occurrence of spontaneous PSW significantly increased after KF inhibition (P < 0.0001) but not after KF disinhibition (P = 0.14). NTS isoguvacine microinjections attenuated the occurrence of all PSW (n = 5, P < 0.01). NTS bicuculline microinjections (n = 6) resulted in spontaneous activation of a disordered PSW pattern and long-lasting suppression of respiratory activity. Pharmacological manipulation of either KF or NTS also triggered profound changes in respiratory postinspiratory VNA. Our results indicate that the s-PSW comprises two functionally distinct components. While the primary s-PSW is generated within the NTS, a KF-mediated laryngeal adductor reflex safeguards the lower airways from aspiration. Synaptic interaction between KF and NTS is required for s-PSW coordination with respiration as well as for proper gating and timing of s-PSW. PMID:24639482

[Sequential prescriptions: Arguments for a change of therapeutic patterns in treatment resistant depressions].

PubMed

Allouche, G

2016-02-01

Among the therapeutic strategies in treatment of resistant depression, the use of sequential prescriptions is discussed here. A number of observations, initially quite isolated and few controlled studies, some large-scale, have been reported, which showed a definite therapeutic effect of certain requirements in sequential treatment of depression. The Sequenced Treatment Alternatives to Relieve Depression Study (STAR*D) is up to now the largest clinical trial exploring treatment strategies in non psychotic resistant depression in real-life conditions with an algorithm of sequential decision. The main conclusions of this study are the following: after two unsuccessful attempts, the chance of remission decreases considerably. A 12-months follow-up showed that the higher the use of the processing steps were high, the more common the relapses were during this period. The pharmacological differences between psychotropic did not cause clinically significant difference. The positive effect of lithium in combination with antidepressants has been known since the work of De Montigny. Antidepressants allow readjustment of physiological sequence involving different monoaminergic systems together. Studies with tricyclic antidepressant-thyroid hormone T3: in depression, decreased norepinephrine at the synaptic receptors believed to cause hypersensitivity of these receptors. Thyroid hormones modulate the activity of adrenergic receptors. There would be a balance of activity between alpha and beta-adrenergic receptors, depending on the bioavailability of thyroid hormones. ECT may in some cases promote pharmacological response in case of previous resistance, or be effective in preventing relapse. Cognitive therapy and antidepressant medications likely have an effect on different types of depression. We can consider the interest of cognitive therapy in a sequential pattern after effective treatment with an antidepressant effect for treatment of residual symptoms, preventing relapses and recurrences, in antidepressant maintenance. These data support the interest of therapeutic strategies based on evolutionary criteria. Sequential models inspired by statistical methods may incorporate the effects of a future treatment by measuring the current one. Copyright © 2015 L’Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.

A chimeric cyclic interferon-α2b peptide induces apoptosis by sequential activation of phosphatidylinositol 3-kinase, protein kinase Cδ and p38 MAP kinase.

PubMed

Blank, V C; Bertucci, L; Furmento, V A; Peña, C; Marino, V J; Roguin, L P

2013-06-10

We have previously demonstrated that tyrosine phosphorylation of STAT1/3 and p38 mitogen-activated protein kinase (p38 MAPK) activation are involved in the apoptotic response triggered by a chimeric cyclic peptide of the interferon-α2b (IFN-α2b) in WISH cells. Since the peptide also induced serine phosphorylation of STAT proteins, in the present study we examined the kinase involved in serine STAT1 phosphorylation and the signaling effectors acting upstream such activation. We first found that p38 MAPK is involved in serine STAT1 phosphorylation, since a reduction of phophoserine-STAT1 levels was evident after incubating WISH cells with cyclic peptide in the presence of a p38 pharmacological inhibitor or a dominant-negative p38 mutant. Next, we demonstrated that the peptide induced activation of protein kinase Cδ (PKCδ). Based on this finding, the role of this kinase was then evaluated. After incubating WISH cells with a PKCδ inhibitor or after decreasing PKCδ expression levels by RNA interference, both peptide-induced serine STAT1 and p38 phosphorylation levels were significantly decreased, indicating that PKCδ functions as an upstream regulator of p38. We also showed that PKCδ and p38 activation stimulated by the peptide was inhibited by a specific pharmacological inhibitor of phosphatidylinositol 3-kinase (PI3K) or by a dominant-negative p85 PI3K-regulatory subunit, suggesting that PI3K is upstream in the signaling cascade. In addition, the role of PI3K and PKCδ in cyclic peptide-induced apoptosis was examined. Both signaling effectors were found to regulate the antiproliferative activity and the apoptotic response triggered by the cyclic peptide in WISH cells. In conclusion, we herein demonstrated that STAT1 serine phosphorylation is mediated by the sequential activation of PI3K, PKCδ and p38 MAPK. This signaling cascade contributes to the antitumor effect induced by the chimeric IFN-α2b cyclic peptide in WISH cells. Copyright © 2013 Elsevier Inc. All rights reserved.

Hybrid Model Predictive Control for Sequential Decision Policies in Adaptive Behavioral Interventions.

PubMed

Dong, Yuwen; Deshpande, Sunil; Rivera, Daniel E; Downs, Danielle S; Savage, Jennifer S

2014-06-01

Control engineering offers a systematic and efficient method to optimize the effectiveness of individually tailored treatment and prevention policies known as adaptive or "just-in-time" behavioral interventions. The nature of these interventions requires assigning dosages at categorical levels, which has been addressed in prior work using Mixed Logical Dynamical (MLD)-based hybrid model predictive control (HMPC) schemes. However, certain requirements of adaptive behavioral interventions that involve sequential decision making have not been comprehensively explored in the literature. This paper presents an extension of the traditional MLD framework for HMPC by representing the requirements of sequential decision policies as mixed-integer linear constraints. This is accomplished with user-specified dosage sequence tables, manipulation of one input at a time, and a switching time strategy for assigning dosages at time intervals less frequent than the measurement sampling interval. A model developed for a gestational weight gain (GWG) intervention is used to illustrate the generation of these sequential decision policies and their effectiveness for implementing adaptive behavioral interventions involving multiple components.

How to Compress Sequential Memory Patterns into Periodic Oscillations: General Reduction Rules

PubMed Central

Zhang, Kechen

2017-01-01

A neural network with symmetric reciprocal connections always admits a Lyapunov function, whose minima correspond to the memory states stored in the network. Networks with suitable asymmetric connections can store and retrieve a sequence of memory patterns, but the dynamics of these networks cannot be characterized as readily as that of the symmetric networks due to the lack of established general methods. Here, a reduction method is developed for a class of asymmetric attractor networks that store sequences of activity patterns as associative memories, as in a Hopfield network. The method projects the original activity pattern of the network to a low-dimensional space such that sequential memory retrievals in the original network correspond to periodic oscillations in the reduced system. The reduced system is self-contained and provides quantitative information about the stability and speed of sequential memory retrievals in the original network. The time evolution of the overlaps between the network state and the stored memory patterns can also be determined from extended reduced systems. The reduction procedure can be summarized by a few reduction rules, which are applied to several network models, including coupled networks and networks with time-delayed connections, and the analytical solutions of the reduced systems are confirmed by numerical simulations of the original networks. Finally, a local learning rule that provides an approximation to the connection weights involving the pseudoinverse is also presented. PMID:24877729

A rational workflow for sequential virtual screening of chemical libraries on searching for new tyrosinase inhibitors.

PubMed

Le-Thi-Thu, Huong; Casanola-Martín, Gerardo M; Marrero-Ponce, Yovani; Rescigno, Antonio; Abad, Concepcion; Khan, Mahmud Tareq Hassan

2014-01-01

The tyrosinase is a bifunctional, copper-containing enzyme widely distributed in the phylogenetic tree. This enzyme is involved in the production of melanin and some other pigments in humans, animals and plants, including skin pigmentations in mammals, and browning process in plants and vegetables. Therefore, enzyme inhibitors has been under the attention of the scientist community, due to its broad applications in food, cosmetic, agricultural and medicinal fields, to avoid the undesirable effects of abnormal melanin overproduction. However, the research of novel chemical with antityrosinase activity demands the use of more efficient tools to speed up the tyrosinase inhibitors discovery process. This chapter is focused in the different components of a predictive modeling workflow for the identification and prioritization of potential new compounds with activity against the tyrosinase enzyme. In this case, two structure chemical libraries Spectrum Collection and Drugbank are used in this attempt to combine different virtual screening data mining techniques, in a sequential manner helping to avoid the usually expensive and time consuming traditional methods. Some of the sequential steps summarize here comprise the use of drug-likeness filters, similarity searching, classification and potency QSAR multiclassifier systems, modeling molecular interactions systems, and similarity/diversity analysis. Finally, the methodologies showed here provide a rational workflow for virtual screening hit analysis and selection as a promissory drug discovery strategy for use in target identification phase.

Metataxonomic profiling and prediction of functional behaviour of wheat straw degrading microbial consortia

PubMed Central

2014-01-01

Background Mixed microbial cultures, in which bacteria and fungi interact, have been proposed as an efficient way to deconstruct plant waste. The characterization of specific microbial consortia could be the starting point for novel biotechnological applications related to the efficient conversion of lignocellulose to cello-oligosaccharides, plastics and/or biofuels. Here, the diversity, composition and predicted functional profiles of novel bacterial-fungal consortia are reported, on the basis of replicated aerobic wheat straw enrichment cultures. Results In order to set up biodegradative microcosms, microbial communities were retrieved from a forest soil and introduced into a mineral salt medium containing 1% of (un)treated wheat straw. Following each incubation step, sequential transfers were carried out using 1 to 1,000 dilutions. The microbial source next to three sequential batch cultures (transfers 1, 3 and 10) were analyzed by bacterial 16S rRNA gene and fungal ITS1 pyrosequencing. Faith’s phylogenetic diversity values became progressively smaller from the inoculum to the sequential batch cultures. Moreover, increases in the relative abundances of Enterobacteriales, Pseudomonadales, Flavobacteriales and Sphingobacteriales were noted along the enrichment process. Operational taxonomic units affiliated with Acinetobacter johnsonii, Pseudomonas putida and Sphingobacterium faecium were abundant and the underlying strains were successfully isolated. Interestingly, Klebsiella variicola (OTU1062) was found to dominate in both consortia, whereas K. variicola-affiliated strains retrieved from untreated wheat straw consortia showed endoglucanase/xylanase activities. Among the fungal players with high biotechnological relevance, we recovered members of the genera Penicillium, Acremonium, Coniochaeta and Trichosporon. Remarkably, the presence of peroxidases, alpha-L-fucosidases, beta-xylosidases, beta-mannases and beta-glucosidases, involved in lignocellulose degradation, was indicated by predictive bacterial metagenome reconstruction. Reassuringly, tests for specific (hemi)cellulolytic enzymatic activities, performed on the consortial secretomes, confirmed the presence of such gene functions. Conclusion In an in-depth characterization of two wheat straw degrading microbial consortia, we revealed the enrichment and selection of specific bacterial and fungal taxa that were presumably involved in (hemi) cellulose degradation. Interestingly, the microbial community composition was strongly influenced by the wheat straw pretreatment. Finally, the functional bacterial-metagenome prediction and the evaluation of enzymatic activities (at the consortial secretomes) revealed the presence and enrichment of proteins involved in the deconstruction of plant biomass. PMID:24955113

A Systematic Approach to Subgroup Classification in Intellectual Disability

ERIC Educational Resources Information Center

Schalock, Robert L.; Luckasson, Ruth

2015-01-01

This article describes a systematic approach to subgroup classification based on a classification framework and sequential steps involved in the subgrouping process. The sequential steps are stating the purpose of the classification, identifying the classification elements, using relevant information, and using clearly stated and purposeful…

A Metacognitive Visuospatial Working Memory Training for Children

ERIC Educational Resources Information Center

Caviola, Sara; Mammarella, Irene C.; Cornoldi, Cesare; Lucangeli, Daniela

2009-01-01

The paper studies whether visuospatial working memory (VSWM) and, specifically, recall of sequential-spatial information, can be improved by metacognitive training. Twenty-two fourth-grade children were involved in seven sessions of sequential-spatial memory training, while twenty-four children attended lessons given by their teacher. The…

A behavioural and neural evaluation of prospective decision-making under risk

PubMed Central

Symmonds, Mkael; Bossaerts, Peter; Dolan, Raymond J.

2010-01-01

Making the best choice when faced with a chain of decisions requires a person to judge both anticipated outcomes and future actions. Although economic decision-making models account for both risk and reward in single choice contexts there is a dearth of similar knowledge about sequential choice. Classical utility-based models assume that decision-makers select and follow an optimal pre-determined strategy, irrespective of the particular order in which options are presented. An alternative model involves continuously re-evaluating decision utilities, without prescribing a specific future set of choices. Here, using behavioral and functional magnetic resonance imaging (fMRI) data, we studied human subjects in a sequential choice task and use these data to compare alternative decision models of valuation and strategy selection. We provide evidence that subjects adopt a model of re-evaluating decision utilities, where available strategies are continuously updated and combined in assessing action values. We validate this model by using simultaneously-acquired fMRI data to show that sequential choice evokes a pattern of neural response consistent with a tracking of anticipated distribution of future reward, as expected in such a model. Thus, brain activity evoked at each decision point reflects the expected mean, variance and skewness of possible payoffs, consistent with the idea that sequential choice evokes a prospective evaluation of both available strategies and possible outcomes. PMID:20980595

A behavioral and neural evaluation of prospective decision-making under risk.

PubMed

Symmonds, Mkael; Bossaerts, Peter; Dolan, Raymond J

2010-10-27

Making the best choice when faced with a chain of decisions requires a person to judge both anticipated outcomes and future actions. Although economic decision-making models account for both risk and reward in single-choice contexts, there is a dearth of similar knowledge about sequential choice. Classical utility-based models assume that decision-makers select and follow an optimal predetermined strategy, regardless of the particular order in which options are presented. An alternative model involves continuously reevaluating decision utilities, without prescribing a specific future set of choices. Here, using behavioral and functional magnetic resonance imaging (fMRI) data, we studied human subjects in a sequential choice task and use these data to compare alternative decision models of valuation and strategy selection. We provide evidence that subjects adopt a model of reevaluating decision utilities, in which available strategies are continuously updated and combined in assessing action values. We validate this model by using simultaneously acquired fMRI data to show that sequential choice evokes a pattern of neural response consistent with a tracking of anticipated distribution of future reward, as expected in such a model. Thus, brain activity evoked at each decision point reflects the expected mean, variance, and skewness of possible payoffs, consistent with the idea that sequential choice evokes a prospective evaluation of both available strategies and possible outcomes.

Accurate means of detecting and characterizing abnormal patterns of ventricular activation by phase image analysis

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

Botvinick, E.H.; Frais, M.A.; Shosa, D.W.

1982-08-01

The ability of scintigraphic phase image analysis to characterize patterns of abnormal ventricular activation was investigated. The pattern of phase distribution and sequential phase changes over both right and left ventricular regions of interest were evaluated in 16 patients with normal electrical activation and wall motion and compared with those in 8 patients with an artificial pacemaker and 4 patients with sinus rhythm with the Wolff-Parkinson-White syndrome and delta waves. Normally, the site of earliest phase angle was seen at the base of the interventricular septum, with sequential change affecting the body of the septum and the cardiac apex andmore » then spreading laterally to involve the body of both ventricles. The site of earliest phase angle was located at the apex of the right ventricle in seven patients with a right ventricular endocardial pacemaker and on the lateral left ventricular wall in one patient with a left ventricular epicardial pacemaker. In each case the site corresponded exactly to the position of the pacing electrode as seen on posteroanterior and left lateral chest X-ray films, and sequential phase changes spread from the initial focus to affect both ventricles. In each of the patients with the Wolff-Parkinson-White syndrome, the site of earliest ventricular phase angle was located, and it corresponded exactly to the site of the bypass tract as determined by endocardial mapping. In this way, four bypass pathways, two posterior left paraseptal, one left lateral and one right lateral, were correctly localized scintigraphically. On the basis of the sequence of mechanical contraction, phase image analysis provides an accurate noninvasive method of detecting abnormal foci of ventricular activation.« less

Reactivation, Replay, and Preplay: How It Might All Fit Together

PubMed Central

Buhry, Laure; Azizi, Amir H.; Cheng, Sen

2011-01-01

Sequential activation of neurons that occurs during “offline” states, such as sleep or awake rest, is correlated with neural sequences recorded during preceding exploration phases. This so-called reactivation, or replay, has been observed in a number of different brain regions such as the striatum, prefrontal cortex, primary visual cortex and, most prominently, the hippocampus. Reactivation largely co-occurs together with hippocampal sharp-waves/ripples, brief high-frequency bursts in the local field potential. Here, we first review the mounting evidence for the hypothesis that reactivation is the neural mechanism for memory consolidation during sleep. We then discuss recent results that suggest that offline sequential activity in the waking state might not be simple repetitions of previously experienced sequences. Some offline sequential activity occurs before animals are exposed to a novel environment for the first time, and some sequences activated offline correspond to trajectories never experienced by the animal. We propose a conceptual framework for the dynamics of offline sequential activity that can parsimoniously describe a broad spectrum of experimental results. These results point to a potentially broader role of offline sequential activity in cognitive functions such as maintenance of spatial representation, learning, or planning. PMID:21918724

A model for sequential decoding overflow due to a noisy carrier reference. [communication performance prediction

NASA Technical Reports Server (NTRS)

Layland, J. W.

1974-01-01

An approximate analysis of the effect of a noisy carrier reference on the performance of sequential decoding is presented. The analysis uses previously developed techniques for evaluating noisy reference performance for medium-rate uncoded communications adapted to sequential decoding for data rates of 8 to 2048 bits/s. In estimating the ten to the minus fourth power deletion probability thresholds for Helios, the model agrees with experimental data to within the experimental tolerances. The computational problem involved in sequential decoding, carrier loop effects, the main characteristics of the medium-rate model, modeled decoding performance, and perspectives on future work are discussed.

A phosphine mediated sequential annulation process of 2-tosylaminochalcones with MBH carbonates to construct functionalized aza-benzobicyclo[4.3.0] derivatives.

PubMed

Zhang, Qinglong; Zhu, Yannan; Jin, Hongxing; Huang, You

2017-04-04

A novel phosphine mediated sequential annulation process to construct functionalized aza-benzobicyclo[4.3.0] derivatives has been developed involving a one-pot sequential catalytic and stoichiometric process, which generates a series of benzobicyclo[4.3.0] compounds containing one quaternary center with up to 94% yield and 20 : 1 dr value. In this reaction, MBH carbonates act as 1,2,3-C 3 synthons.

Atoh1-dependent rhombic lip neurons are required for temporal delay between independent respiratory oscillators in embryonic mice

PubMed Central

Tupal, Srinivasan; Huang, Wei-Hsiang; Picardo, Maria Cristina D; Ling, Guang-Yi; Del Negro, Christopher A; Zoghbi, Huda Y; Gray, Paul A

2014-01-01

All motor behaviors require precise temporal coordination of different muscle groups. Breathing, for example, involves the sequential activation of numerous muscles hypothesized to be driven by a primary respiratory oscillator, the preBötzinger Complex, and at least one other as-yet unidentified rhythmogenic population. We tested the roles of Atoh1-, Phox2b-, and Dbx1-derived neurons (three groups that have known roles in respiration) in the generation and coordination of respiratory output. We found that Dbx1-derived neurons are necessary for all respiratory behaviors, whereas independent but coupled respiratory rhythms persist from at least three different motor pools after eliminating or silencing Phox2b- or Atoh1-expressing hindbrain neurons. Without Atoh1 neurons, however, the motor pools become temporally disorganized and coupling between independent respiratory oscillators decreases. We propose Atoh1 neurons tune the sequential activation of independent oscillators essential for the fine control of different muscles during breathing. DOI: http://dx.doi.org/10.7554/eLife.02265.001 PMID:24842997

Sequential Logic Model Deciphers Dynamic Transcriptional Control of Gene Expressions

PubMed Central

Yeo, Zhen Xuan; Wong, Sum Thai; Arjunan, Satya Nanda Vel; Piras, Vincent; Tomita, Masaru; Selvarajoo, Kumar; Giuliani, Alessandro; Tsuchiya, Masa

2007-01-01

Background Cellular signaling involves a sequence of events from ligand binding to membrane receptors through transcription factors activation and the induction of mRNA expression. The transcriptional-regulatory system plays a pivotal role in the control of gene expression. A novel computational approach to the study of gene regulation circuits is presented here. Methodology Based on the concept of finite state machine, which provides a discrete view of gene regulation, a novel sequential logic model (SLM) is developed to decipher control mechanisms of dynamic transcriptional regulation of gene expressions. The SLM technique is also used to systematically analyze the dynamic function of transcriptional inputs, the dependency and cooperativity, such as synergy effect, among the binding sites with respect to when, how much and how fast the gene of interest is expressed. Principal Findings SLM is verified by a set of well studied expression data on endo16 of Strongylocentrotus purpuratus (sea urchin) during the embryonic midgut development. A dynamic regulatory mechanism for endo16 expression controlled by three binding sites, UI, R and Otx is identified and demonstrated to be consistent with experimental findings. Furthermore, we show that during transition from specification to differentiation in wild type endo16 expression profile, SLM reveals three binary activities are not sufficient to explain the transcriptional regulation of endo16 expression and additional activities of binding sites are required. Further analyses suggest detailed mechanism of R switch activity where indirect dependency occurs in between UI activity and R switch during specification to differentiation stage. Conclusions/Significance The sequential logic formalism allows for a simplification of regulation network dynamics going from a continuous to a discrete representation of gene activation in time. In effect our SLM is non-parametric and model-independent, yet providing rich biological insight. The demonstration of the efficacy of this approach in endo16 is a promising step for further application of the proposed method. PMID:17712424

Aging and sequential modulations of poorer strategy effects: An EEG study in arithmetic problem solving.

PubMed

Hinault, Thomas; Lemaire, Patrick; Phillips, Natalie

2016-01-01

This study investigated age-related differences in electrophysiological signatures of sequential modulations of poorer strategy effects. Sequential modulations of poorer strategy effects refer to decreased poorer strategy effects (i.e., poorer performance when the cued strategy is not the best) on current problem following poorer strategy problems compared to after better strategy problems. Analyses on electrophysiological (EEG) data revealed important age-related changes in time, frequency, and coherence of brain activities underlying sequential modulations of poorer strategy effects. More specifically, sequential modulations of poorer strategy effects were associated with earlier and later time windows (i.e., between 200- and 550 ms and between 850- and 1250 ms). Event-related potentials (ERPs) also revealed an earlier onset in older adults, together with more anterior and less lateralized activations. Furthermore, sequential modulations of poorer strategy effects were associated with theta and alpha frequencies in young adults while these modulations were found in delta frequency and theta inter-hemispheric coherence in older adults, consistent with qualitatively distinct patterns of brain activity. These findings have important implications to further our understanding of age-related differences and similarities in sequential modulations of cognitive control processes during arithmetic strategy execution. Copyright © 2015 Elsevier B.V. All rights reserved.

Reorganization of large-scale cognitive networks during automation of imagination of a complex sequential movement.

PubMed

Sauvage, C; De Greef, N; Manto, M; Jissendi, P; Nioche, C; Habas, C

2015-04-01

We investigated the functional reconfiguration of the cerebral networks involved in imagination of sequential movements of the left foot, both performed at regular and fast speed after mental imagery training. Thirty-five volunteers were scanned with a 3T MRI while they imagined a sequence of ankle movements (dorsiflexion, plantar flexion, varus and valgus) before and after mental practice. Subjects were distributed in two groups: the first group executed regular movements whereas the second group made fast movements. We applied the general linear model (GLM) and model-free, exploratory tensorial independent component analytic (TICA) approaches to identify plastic post-training effects on brain activation. GLM showed that post-training imagination of movement was accompanied by a dual effect: a specific recruitment of a medial prefronto-cingulo-parietal circuit reminiscent of the default-mode network, with the left putamen, and a decreased activity of a lateral fronto-parietal network. Training-related subcortical changes only consisted in an increased activity in the left striatum. Unexpectedly, no difference was observed in the cerebellum. TICA also revealed involvement of the left executive network, and of the dorsal control executive network but no significant differences were found between pre- and post-training phases. Therefore, repetitive motor mental imagery induced specific putamen (motor rehearsal) recruitment that one previously observed during learning of overt movements, and, simultaneously, a specific shift of activity from the dorsolateral prefrontal cortex (attention, working memory) to the medial posterior parietal and cingulate cortices (mental imagery and memory rehearsal). Our data complement and confirm the notion that differential and coupled recruitment of cognitive networks can constitute a neural marker of training effects. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Efficacy of sequential or simultaneous interactive computer-tailored interventions for increasing physical activity and decreasing fat intake.

PubMed

Vandelanotte, Corneel; De Bourdeaudhuij, Ilse; Sallis, James F; Spittaels, Heleen; Brug, Johannes

2005-04-01

Little evidence exists about the effectiveness of "interactive" computer-tailored interventions and about the combined effectiveness of tailored interventions on physical activity and diet. Furthermore, it is unknown whether they should be executed sequentially or simultaneously. The purpose of this study was to examine (a) the effectiveness of interactive computer-tailored interventions for increasing physical activity and decreasing fat intake and (b) which intervening mode, sequential or simultaneous, is most effective in behavior change. Participants (N = 771) were randomly assigned to receive (a) the physical activity and fat intake interventions simultaneously at baseline, (b) the physical activity intervention at baseline and the fat intake intervention 3 months later, (c) the fat intake intervention at baseline and the physical activity intervention 3 months later, or (d) a place in the control group. Six months postbaseline, the results showed that the tailored interventions produced significantly higher physical activity scores, F(2, 573) = 11.4, p < .001, and lower fat intake scores, F(2, 565) = 31.4, p < .001, in the experimental groups when compared to the control group. For both behaviors, the sequential and simultaneous intervening modes showed to be effective; however, for the fat intake intervention and for the participants who did not meet the recommendation in the physical activity intervention, the simultaneous mode appeared to work better than the sequential mode.

The effect of a sequential structure of practice for the training of perceptual-cognitive skills in tennis

PubMed Central

2017-01-01

Objective Anticipation of opponent actions, through the use of advanced (i.e., pre-event) kinematic information, can be trained using video-based temporal occlusion. Typically, this involves isolated opponent skills/shots presented as trials in a random order. However, two different areas of research concerning representative task design and contextual (non-kinematic) information, suggest this structure of practice restricts expert performance. The aim of this study was to examine the effect of a sequential structure of practice during video-based training of anticipatory behavior in tennis, as well as the transfer of these skills to the performance environment. Methods In a pre-practice-retention-transfer design, participants viewed life-sized video of tennis rallies across practice in either a sequential order (sequential group), in which participants were exposed to opponent skills/shots in the order they occur in the sport, or a non-sequential (non-sequential group) random order. Results In the video-based retention test, the sequential group was significantly more accurate in their anticipatory judgments when the retention condition replicated the sequential structure compared to the non-sequential group. In the non-sequential retention condition, the non-sequential group was more accurate than the sequential group. In the field-based transfer test, overall decision time was significantly faster in the sequential group compared to the non-sequential group. Conclusion Findings highlight the benefits of a sequential structure of practice for the transfer of anticipatory behavior in tennis. We discuss the role of contextual information, and the importance of representative task design, for the testing and training of perceptual-cognitive skills in sport. PMID:28355263

Children's Reproduction of Modeled Sequential Actions. Final Report.

ERIC Educational Resources Information Center

Uzgiris, Ina C.

This paper describes seven interrelated studies concerned with children's understanding of sequential actions and with the effects of observing a model on this understanding. A total of 546 elementary and secondary school students served as subjects for the studies. The tasks for all of the studies involved deriving the pattern for a sequence from…

The NADPH Oxidases DUOX1 and NOX2 Play Distinct Roles in Redox Regulation of Epidermal Growth Factor Receptor Signaling.

PubMed

Heppner, David E; Hristova, Milena; Dustin, Christopher M; Danyal, Karamatullah; Habibovic, Aida; van der Vliet, Albert

2016-10-28

The epidermal growth factor receptor (EGFR) plays a critical role in regulating airway epithelial homeostasis and responses to injury. Activation of EGFR is regulated by redox-dependent processes involving reversible cysteine oxidation by reactive oxygen species (ROS) and involves both ligand-dependent and -independent mechanisms, but the precise source(s) of ROS and the molecular mechanisms that control tyrosine kinase activity are incompletely understood. Here, we demonstrate that stimulation of EGFR activation by ATP in airway epithelial cells is closely associated with dynamic reversible oxidation of cysteine residues via sequential sulfenylation and S-glutathionylation within EGFR and the non-receptor-tyrosine kinase Src. Moreover, the intrinsic kinase activity of recombinant Src or EGFR was in both cases enhanced by H 2 O 2 but not by GSSG, indicating that the intermediate sulfenylation is the activating modification. H 2 O 2 -induced increase in EGFR tyrosine kinase activity was not observed with the C797S variant, confirming Cys-797 as the redox-sensitive cysteine residue that regulates kinase activity. Redox-dependent regulation of EGFR activation in airway epithelial cells was found to strongly depend on activation of either the NADPH oxidase DUOX1 or the homolog NOX2, depending on the activation mechanism. Whereas DUOX1 and Src play a primary role in EGFR transactivation by wound-derived signals such as ATP, direct ligand-dependent EGFR activation primarily involves NOX2 with a secondary role for DUOX1 and Src. Collectively, our findings establish that redox-dependent EGFR kinase activation involves a dynamic and reversible cysteine oxidation mechanism and that this activation mechanism variably involves DUOX1 and NOX2. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Sequential analysis in neonatal research-systematic review.

PubMed

Lava, Sebastiano A G; Elie, Valéry; Ha, Phuong Thi Viet; Jacqz-Aigrain, Evelyne

2018-05-01

As more new drugs are discovered, traditional designs come at their limits. Ten years after the adoption of the European Paediatric Regulation, we performed a systematic review on the US National Library of Medicine and Excerpta Medica database of sequential trials involving newborns. Out of 326 identified scientific reports, 21 trials were included. They enrolled 2832 patients, of whom 2099 were analyzed: the median number of neonates included per trial was 48 (IQR 22-87), median gestational age was 28.7 (IQR 27.9-30.9) weeks. Eighteen trials used sequential techniques to determine sample size, while 3 used continual reassessment methods for dose-finding. In 16 studies reporting sufficient data, the sequential design allowed to non-significantly reduce the number of enrolled neonates by a median of 24 (31%) patients (IQR - 4.75 to 136.5, p = 0.0674) with respect to a traditional trial. When the number of neonates finally included in the analysis was considered, the difference became significant: 35 (57%) patients (IQR 10 to 136.5, p = 0.0033). Sequential trial designs have not been frequently used in Neonatology. They might potentially be able to reduce the number of patients in drug trials, although this is not always the case. What is known: • In evaluating rare diseases in fragile populations, traditional designs come at their limits. About 20% of pediatric trials are discontinued, mainly because of recruitment problems. What is new: • Sequential trials involving newborns were infrequently used and only a few (n = 21) are available for analysis. • The sequential design allowed to non-significantly reduce the number of enrolled neonates by a median of 24 (31%) patients (IQR - 4.75 to 136.5, p = 0.0674).

Human sympathetic and vagal baroreflex responses to sequential nitroprusside and phenylephrine

NASA Technical Reports Server (NTRS)

Rudas, L.; Crossman, A. A.; Morillo, C. A.; Halliwill, J. R.; Tahvanainen, K. U.; Kuusela, T. A.; Eckberg, D. L.

1999-01-01

We evaluated a method of baroreflex testing involving sequential intravenous bolus injections of nitroprusside followed by phenylephrine and phenylephrine followed by nitroprusside in 18 healthy men and women, and we drew inferences regarding human sympathetic and vagal baroreflex mechanisms. We recorded the electrocardiogram, photoplethysmographic finger arterial pressure, and peroneal nerve muscle sympathetic activity. We then contrasted least squares linear regression slopes derived from the depressor (nitroprusside) and pressor (phenylephrine) phases with 1) slopes derived from spontaneous fluctuations of systolic arterial pressures and R-R intervals, and 2) baroreflex gain derived from cross-spectral analyses of systolic pressures and R-R intervals. We calculated sympathetic baroreflex gain from integrated muscle sympathetic nerve activity and diastolic pressures. We found that vagal baroreflex slopes are less when arterial pressures are falling than when they are rising and that this hysteresis exists over pressure ranges both below and above baseline levels. Although pharmacological and spontaneous vagal baroreflex responses correlate closely, pharmacological baroreflex slopes tend to be lower than those derived from spontaneous fluctuations. Sympathetic baroreflex slopes are similar when arterial pressure is falling and rising; however, small pressure elevations above baseline silence sympathetic motoneurons. Vagal, but not sympathetic baroreflex gains vary inversely with subjects' ages and their baseline arterial pressures. There is no correlation between sympathetic and vagal baroreflex gains. We recommend repeated sequential nitroprusside followed by phenylephrine doses as a simple, efficientmeans to provoke and characterize human vagal and sympathetic baroreflex responses.

Active Thermochemical Tables: Sequential Bond Dissociation Enthalpies of Methane, Ethane, and Methanol and the Related Thermochemistry

DOE PAGES

Ruscic, Branko

2015-03-31

Active Thermochemical Tables (ATcT) thermochemistry for the sequential bond dissociations of methane, ethane, and methanol systems were obtained by analyzing and solving a very large thermochemical network (TN). Values for all possible C–H, C–C, C–O, and O–H bond dissociation enthalpies at 298.15 K (BDE 298) and bond dissociation energies at 0 K (D 0) are presented. The corresponding ATcT standard gas-phase enthalpies of formation of the resulting CH n, n = 4–0 species (methane, methyl, methylene, methylidyne, and carbon atom), C 2H n, n = 6–0 species (ethane, ethyl, ethylene, ethylidene, vinyl, ethylidyne, acetylene, vinylidene, ethynyl, and ethynylene), and COHmore » n, n = 4–0 species (methanol, hydroxymethyl, methoxy, formaldehyde, hydroxymethylene, formyl, isoformyl, and carbon monoxide) are also presented. The ATcT thermochemistry of carbon dioxide, water, hydroxyl, and carbon, oxygen, and hydrogen atoms is also included, together with the sequential BDEs of CO 2 and H 2O. The provenances of the ATcT enthalpies of formation, which are quite distributed and involve a large number of relevant determinations, are analyzed by variance decomposition and discussed in terms of principal contributions. The underlying reasons for periodic appearances of remarkably low and/or unusually high BDEs, alternating along the dissociation sequences, are analyzed and quantitatively rationalized. The present ATcT results are the most accurate thermochemical values currently available for these species.« less

Serotonin syndrome following sibutramine poisoning in a child, with sequential quantification of sibutramine and its primary and secondary amine metabolites in plasma.

PubMed

Bucaretchi, Fábio; de Capitani, Eduardo Mello; Mello, Sueli Moreira; Lanaro, Rafael; Barros, Roberta F; Fernandes, Luciane C R; da Costa, José Luiz; Hyslop, Stephen

2009-07-01

To report a case of serotonin syndrome (SS) after sibutramine overdose in a child. A 4-year-old girl was admitted 25 h after accidentally ingesting approximately 27 pills of sibutramine (15 mg, approximately 23 mg/kg). The child developed clinical features suggestive of SS, including diaphoresis, tachycardia, hypertension, agitation, insomnia, incoordination, hypertonia (lower limbs > upper limbs), and hallucinations. Serum creatine phosphokinase levels reached a peak on day 3 (2,577 U/L, reference value <145), suggesting mild rhabdomyolysis. No relevant changes were detected in other laboratory examinations or in the electrocardiogram throughout the period of hospitalization. The quantification of sibutramine and the active metabolites, M1 (mono-desmethyl sibutramine) and M2 (di-desmethyl sibutramine), by liquid chromatography/electrospray ionization tandem mass spectrometry in six sequential samples collected from 25 to 147 h post-ingestion revealed a nonlinear decrease in the log-scale plasma concentrations. Treatment was only supportive and involved prolonged sedation to control the agitation, sleeplessness, and hypertension; no cyproheptadine was used. The patient was discharged on day 6 and follow-up revealed no sequelae. To our knowledge, this is the first report of SS after sibutramine overdose in a child, with sequential monitoring of the plasma levels of the drug and its two active metabolites. The growing consumption of weight reducing pills may increase the risk of unintentional acute toxic exposures in children.

An Initial Analysis of Learning Styles Exhibited by High School Science Students

NASA Astrophysics Data System (ADS)

Donelson, Frederick; Bensel, H.; Miller, D.; Seebode, S.; Ciardi, D. R.; Howell, S. B.

2014-01-01

Educational research magazines are filled with information on learning styles and how they affect the learning process, but few studies have been conducted to specifically look at learning styles exhibited by high school science students. This project attempted to obtain a general “snapshot” of learning styles found in the high school science classroom, and then compare that to one derived from a subgroup of highly motivated science students involved in a NITARP student team. Control students (N=54) from elective science courses at four high schools (urban, suburban, and rural) were administered the Felder Learning Style (FLS) assessment and rated on Likert scales in four learning constructs: Active/Reflective, Sensing/Intuitive, Visual/Verbal, and Sequential/Global. NITARP student team members (N=7) were given the FLS before project work began, and then re-tested approximately three months later, after project work concluded. Chi Square Analysis showed no clear significant difference between the general group and the NITARP group (p = .52). Both groups tended to be very visual and sequential, but more reflective than active. The results suggest several concerns that science teachers may need to address: (1) Research shows best practice science classes often are hands on, yet a majority of students are more reflective than active; (2) Big ideas tend to be better understood by global students, but a majority are more sequential; (3) Since a majority of students are visual, information given verbally may not be very effective. Further research is indicated for these areas of discontinuity. This research was conducted as part of the NASA/IPAC Training in Archival Research Project (NITARP) and was funded by NASA Astrophysics Data Program and Archive Outreach funds.

Structural and Functional Impacts of ER Coactivator Sequential Recruitment.

PubMed

Yi, Ping; Wang, Zhao; Feng, Qin; Chou, Chao-Kai; Pintilie, Grigore D; Shen, Hong; Foulds, Charles E; Fan, Guizhen; Serysheva, Irina; Ludtke, Steven J; Schmid, Michael F; Hung, Mien-Chie; Chiu, Wah; O'Malley, Bert W

2017-09-07

Nuclear receptors recruit multiple coactivators sequentially to activate transcription. This "ordered" recruitment allows different coactivator activities to engage the nuclear receptor complex at different steps of transcription. Estrogen receptor (ER) recruits steroid receptor coactivator-3 (SRC-3) primary coactivator and secondary coactivators, p300/CBP and CARM1. CARM1 recruitment lags behind the binding of SRC-3 and p300 to ER. Combining cryo-electron microscopy (cryo-EM) structure analysis and biochemical approaches, we demonstrate that there is a close crosstalk between early- and late-recruited coactivators. The sequential recruitment of CARM1 not only adds a protein arginine methyltransferase activity to the ER-coactivator complex, it also alters the structural organization of the pre-existing ERE/ERα/SRC-3/p300 complex. It induces a p300 conformational change and significantly increases p300 HAT activity on histone H3K18 residues, which, in turn, promotes CARM1 methylation activity on H3R17 residues to enhance transcriptional activity. This study reveals a structural role for a coactivator sequential recruitment and biochemical process in ER-mediated transcription. Copyright © 2017 Elsevier Inc. All rights reserved.

Sequential analysis applied to clinical trials in dentistry: a systematic review.

PubMed

Bogowicz, P; Flores-Mir, C; Major, P W; Heo, G

2008-01-01

Clinical trials employ sequential analysis for the ethical and economic benefits it brings. In dentistry, as in other fields, resources are scarce and efforts are made to ensure that patients are treated ethically. The objective of this systematic review was to characterise the use of sequential analysis for clinical trials in dentistry. We searched various databases from 1900 through to January 2008. Articles were selected for review if they were clinical trials in the field of dentistry that had applied some form of sequential analysis. Selection was carried out independently by two of the authors. We included 18 trials from various specialties, which involved many different interventions. We conclude that sequential analysis seems to be underused in this field but that there are sufficient methodological resources in place for future applications.Evidence-Based Dentistry (2008) 9, 55-62. doi:10.1038/sj.ebd.6400587.

A sequential solution for anisotropic total variation image denoising with interval constraints

NASA Astrophysics Data System (ADS)

Xu, Jingyan; Noo, Frédéric

2017-09-01

We show that two problems involving the anisotropic total variation (TV) and interval constraints on the unknown variables admit, under some conditions, a simple sequential solution. Problem 1 is a constrained TV penalized image denoising problem; problem 2 is a constrained fused lasso signal approximator. The sequential solution entails finding first the solution to the unconstrained problem, and then applying a thresholding to satisfy the constraints. If the interval constraints are uniform, this sequential solution solves problem 1. If the interval constraints furthermore contain zero, the sequential solution solves problem 2. Here uniform interval constraints refer to all unknowns being constrained to the same interval. A typical example of application is image denoising in x-ray CT, where the image intensities are non-negative as they physically represent linear attenuation coefficient in the patient body. Our results are simple yet seem unknown; we establish them using the Karush-Kuhn-Tucker conditions for constrained convex optimization.

Comparison of Sequential Drug Release in Vitro and in Vivo

PubMed Central

Sundararaj, Sharath C.; Al-Sabbagh, Mohanad; Rabek, Cheryl L.; Dziubla, Thomas D.; Thomas, Mark V.; Puleo, David A.

2015-01-01

Development of drug delivery devices typically involves characterizing in vitro release performance with the inherent assumption that this will closely approximate in vivo performance. Yet, as delivery devices become more complex, for instance with a sequential drug release pattern, it is important to confirm that in vivo properties correlate with the expected “programming” achieved in vitro. In this work, a systematic comparison between in vitro and in vivo biomaterial erosion and sequential release was performed for a multilayered association polymer system comprising cellulose acetate phthalate and Pluronic F-127. After assessing the materials during incubation in phosphate-buffered saline, devices were implanted supracalvarially in rats. Devices with two different doses and with different erosion rates were harvested at increasing times post-implantation, and the in vivo thickness loss, mass loss, and the drug release profiles were compared with their in vitro counterparts. The sequential release of four different drugs observed in vitro was successfully translated to in vivo conditions. Results suggest, however, that the total erosion time of the devices was longer and release rates of the four drugs were different, with drugs initially released more quickly and then more slowly in vivo. Whereas many comparative studies of in vitro and in vivo drug release from biodegradable polymers involved a single drug, the present research demonstrated that sequential release of four drugs can be maintained following implantation. PMID:26111338

LKB1 signaling in cephalic neural crest cells is essential for vertebrate head development.

PubMed

Creuzet, Sophie E; Viallet, Jean P; Ghawitian, Maya; Torch, Sakina; Thélu, Jacques; Alrajeh, Moussab; Radu, Anca G; Bouvard, Daniel; Costagliola, Floriane; Borgne, Maïlys Le; Buchet-Poyau, Karine; Aznar, Nicolas; Buschlen, Sylvie; Hosoya, Hiroshi; Thibert, Chantal; Billaud, Marc

2016-10-15

Head development in vertebrates proceeds through a series of elaborate patterning mechanisms and cell-cell interactions involving cephalic neural crest cells (CNCC). These cells undergo extensive migration along stereotypical paths after their separation from the dorsal margins of the neural tube and they give rise to most of the craniofacial skeleton. Here, we report that the silencing of the LKB1 tumor suppressor affects the delamination of pre-migratory CNCC from the neural primordium as well as their polarization and survival, thus resulting in severe facial and brain defects. We further show that LKB1-mediated effects on the development of CNCC involve the sequential activation of the AMP-activated protein kinase (AMPK), the Rho-dependent kinase (ROCK) and the actin-based motor protein myosin II. Collectively, these results establish that the complex morphogenetic processes governing head formation critically depends on the activation of the LKB1 signaling network in CNCC. Copyright © 2016 Elsevier Inc. All rights reserved.

Role of obestatin on growth hormone secretion: An in vitro approach

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

Pazos, Yolanda, E-mail: yolanda.pazos@usc.es; CIBER Fisiopatologia de la Obesidad y Nutricion; Alvarez, Carlos J.P.

Obestatin, the ghrelin-associated peptide, showed to activate MAPK signaling with no effect on Akt nor cell proliferating activity in rat tumor somatotroph cells (growth cells, GC). A sequential analysis of the obestatin transmembrane signaling pathway indicated a route involving the consecutive activation of G{sub i}, PI3k, novel PKC{epsilon}, and Src for ERK1/2 activation. Furthermore, obestatin treatment triggers growth hormone (GH) release in the first 30 min, being more acute at 15 min. At 1 h, obestatin treated cells showed the same levels in GH secretion than controls. Added to this functionality, obestatin was secreted by GC cells. Based on themore » capacity to stimulate GH release from somatotroph cells, obestatin may act directly in the pituitary through an autocrine/paracrine mechanism.« less

Synthesis of amino ester-embedded benzimidazoles: a one-pot sequential protocol under metal-free neutral conditions.

PubMed

Roy, Priyabrata; Bodhak, Chandan; Pramanik, Animesh

2017-02-01

A one-pot three-component protocol has been developed for the synthesis of amino ester-embedded benzimidazoles under metal-free neutral conditions. Sequentially, the methodology involves coupling of an amino ester with 1-fluoro-2-nitrobenzene, reduction of the coupled nitroarene by sodium dithionite, and cyclization of the corresponding diamine with an aldehyde.

Planning and Instruction and the Social Studies Curriculum: A Discourse on Design and Delivery Systems.

ERIC Educational Resources Information Center

Peters, Richard

A model for Continuous-Integrated-Sequential (C/I/S) curricula for social studies education is presented. The design advocated involves ensuring continuity of instruction from grades K-12, an integration of social studies disciplines, and a sequential process of refining and reinforcing concept and skills from grade-to-grade along the K-12…

Evidence-Based Clinical Recommendations for the Administration of the Sequential Motion Rates Task

ERIC Educational Resources Information Center

Icht, Michal; Ben-David, Boaz M.

2018-01-01

The sequential motion rates (SMR) task, that involves rapid and accurate repetitions of a syllable sequence, /pataka/, is a commonly used evaluation tool for oro-motor abilities. Although the SMR is a well-known tool, some aspects of its administration protocol are unspecified. We address the following factors and their role in the SMR protocol:…

Learning Behavior Characterization with Multi-Feature, Hierarchical Activity Sequences

ERIC Educational Resources Information Center

Ye, Cheng; Segedy, James R.; Kinnebrew, John S.; Biswas, Gautam

2015-01-01

This paper discusses Multi-Feature Hierarchical Sequential Pattern Mining, MFH-SPAM, a novel algorithm that efficiently extracts patterns from students' learning activity sequences. This algorithm extends an existing sequential pattern mining algorithm by dynamically selecting the level of specificity for hierarchically-defined features…

Nail gun injuries in residential carpentry: lessons from active injury surveillance.

PubMed

Lipscomb, H J; Dement, J M; Nolan, J; Patterson, D; Li, L

2003-03-01

To describe circumstances surrounding injuries involving nail guns among carpenters, calculate injury rates, identify high risk groups and preventive measures. and setting: Active injury surveillance was used to identify causes of injury among a large cohort of union residential and drywall carpenters. Injured carpenters were interviewed by experienced journeymen; enumeration of workers and hourworked were provided by the union. The combined data allowed definition of a cohort of carpenters, their hours worked, detailed information on the circumstances surrounding injuries, and identification of preventive measures from the perspectives of the injured worker and an experienced investigator. Nail guns were involved in 14% of injuries investigated. Ninety percent of these injuries were the result of the carpenter being struck, most commonly by a nail puncturing a hand or fingers. The injury rate among apprentices was 3.7 per 200 000 hours worked (95% confidence interval (CI) 2.7 to 4.9) compared with a rate of 1.2 among journeymen (95% CI 0.80 to 1.7). While not always the sole contributing factor, a sequential trigger would have likely prevented 65% of the injuries from tools with contact trip triggers. Training, engineering, and policy changes in the workplace and manufacturing arena are all appropriate targets for prevention of these injuries. Use of sequential triggers would likely decrease acute injury rates markedly. Over 70% of injuries among residential carpenters were associated with through nailing tasks (such as nailing studs or blocks, trusses or joists) or toe nailing (angled, corner nailing) as opposed to flat nailing used for sheathing activities; this provides some indication that contact trip tools could be used solely for flat nailing.

Nail gun injuries in residential carpentry: lessons from active injury surveillance

PubMed Central

Lipscomb, H; Dement, J; Nolan, J; Patterson, D; Li, L

2003-01-01

Objective: To describe circumstances surrounding injuries involving nail guns among carpenters, calculate injury rates, identify high risk groups and preventive measures. Methods and setting: Active injury surveillance was used to identify causes of injury among a large cohort of union residential and drywall carpenters. Injured carpenters were interviewed by experienced journeymen; enumeration of workers and hourworked were provided by the union. The combined data allowed definition of a cohort of carpenters, their hours worked, detailed information on the circumstances surrounding injuries, and identification of preventive measures from the perspectives of the injured worker and an experienced investigator. Results: Nail guns were involved in 14% of injuries investigated. Ninety percent of these injuries were the result of the carpenter being struck, most commonly by a nail puncturing a hand or fingers. The injury rate among apprentices was 3.7 per 200 000 hours worked (95% confidence interval (CI) 2.7 to 4.9) compared with a rate of 1.2 among journeymen (95% CI 0.80 to 1.7). While not always the sole contributing factor, a sequential trigger would have likely prevented 65% of the injuries from tools with contact trip triggers. Conclusions: Training, engineering, and policy changes in the workplace and manufacturing arena are all appropriate targets for prevention of these injuries. Use of sequential triggers would likely decrease acute injury rates markedly. Over 70% of injuries among residential carpenters were associated with through nailing tasks (such as nailing studs or blocks, trusses or joists) or toe nailing (angled, corner nailing) as opposed to flat nailing used for sheathing activities; this provides some indication that contact trip tools could be used solely for flat nailing. PMID:12642553

Asymmetric processing of a substrate protein in sequential allosteric cycles of AAA+ nanomachines

NASA Astrophysics Data System (ADS)

Kravats, Andrea N.; Tonddast-Navaei, Sam; Bucher, Ryan J.; Stan, George

2013-09-01

Essential protein quality control includes mechanisms of substrate protein (SP) unfolding and translocation performed by powerful ring-shaped AAA+ (ATPases associated with various cellular activities) nanomachines. These SP remodeling actions are effected by mechanical forces imparted by AAA+ loops that protrude into the central channel. Sequential intra-ring allosteric motions, which underlie repetitive SP-loop interactions, have been proposed to comprise clockwise (CW), counterclockwise (CCW), or random (R) conformational transitions of individual AAA+ subunits. To probe the effect of these allosteric mechanisms on unfoldase and translocase functions, we perform Langevin dynamics simulations of a coarse-grained model of an all-alpha SP processed by the single-ring ClpY ATPase or by the double-ring p97 ATPase. We find that, in all three allosteric mechanisms, the SP undergoes conformational transitions along a common set of pathways, which reveals that the active work provided by the ClpY machine involves single loop-SP interactions. Nevertheless, the rates and yields of SP unfolding and translocation are controlled by mechanism-dependent loop-SP binding events, as illustrated by faster timescales of SP processing in CW allostery compared with CCW and R allostery. The distinct efficacy of allosteric mechanisms is due to the asymmetric collaboration of adjacent subunits, which involves CW-biased structural motions of AAA+ loops and results in CW-compatible torque applied onto the SP. Additional simulations of mutant ClpY rings, which render a subset of subunits catalytically-defective or reduce their SP binding affinity, reveal that subunit-based conformational transitions play the major role in SP remodeling. Based on these results we predict that the minimally functional AAA+ ring includes three active subunits, only two of which are adjacent.

Brentuximab Vedotin in the Front-Line Treatment of Patients With CD30+ Peripheral T-Cell Lymphomas: Results of a Phase I Study

PubMed Central

Fanale, Michelle A.; Horwitz, Steven M.; Forero-Torres, Andres; Bartlett, Nancy L.; Advani, Ranjana H.; Pro, Barbara; Chen, Robert W.; Davies, Andrew; Illidge, Tim; Huebner, Dirk; Kennedy, Dana A.; Shustov, Andrei R.

2014-01-01

Purpose Front-line treatment of peripheral T-cell lymphomas (PTCL) involves regimens such as cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) and results in a 5-year overall survival (OS) rate of less than 50%. This phase I open-label study evaluated the safety and activity of brentuximab vedotin administered sequentially with CHOP or in combination with CHP (CHOP without vincristine) as front-line treatment in patients with CD30+ PTCL. Patients and Methods Patients received sequential treatment (once every 3 weeks) with brentuximab vedotin 1.8 mg/kg (two cycles) followed by CHOP (six cycles) or brentuximab vedotin 1.8 mg/kg plus CHP (BV+CHP) for six cycles (once every 3 weeks). Responders received single-agent brentuximab vedotin for eight to 10 additional cycles (for a total of 16 cycles). The primary objective was assessment of safety; secondary end points included objective response rate, complete remission (CR) rate, progression-free survival rate (PFS), and OS. There were no prespecified comparisons of the two treatment approaches. Results After sequential treatment, 11 (85%) of 13 patients achieved an objective response (CR rate, 62%; estimated 1-year PFS rate, 77%). Grade 3/4 adverse events occurred in eight (62%) of 13 patients. At the end of combination treatment, all patients (n = 26) achieved an objective response (CR rate, 88%; estimated 1-year PFS rate, 71%). All seven patients without anaplastic large-cell lymphoma achieved CR. Grade 3/4 adverse events (≥ 10%) in the combination-treatment group were febrile neutropenia (31%), neutropenia (23%), anemia (15%), and pulmonary embolism (12%). Conclusion Brentuximab vedotin, administered sequentially with CHOP or in combination with CHP, had a manageable safety profile and exhibited substantial antitumor activity in newly diagnosed patients with CD30+ PTCL. A randomized phase III trial is under way, comparing BV+CHP with CHOP (clinical trial No. NCT01777152). PMID:25135998

Electrochemical immunoassay for vitellogenin based on sequential injection using antigen-immobilized magnetic microbeads.

PubMed

Hirakawa, Koji; Katayama, Masaaki; Soh, Nobuaki; Nakano, Koji; Imato, Toshihiko

2006-01-01

A rapid and sensitive immunoassay for the determination of vitellogenin (Vg) is described. The method involves a sequential injection analysis (SIA) system equipped with an amperometric detector and a neodymium magnet. Magnetic beads, onto which an antigen (Vg) was immobilized, were used as a solid support in an immunoassay. The introduction, trapping and release of magnetic beads in an immunoreaction cell were controlled by means of the neodymium magnet and by adjusting the flow of the carrier solution. The immunoassay was based on an indirect competitive immunoreaction of an alkaline phosphatase (ALP) labeled anti-Vg monoclonal antibody between the fraction of Vg immobilized on the magnetic beads and Vg in the sample solution. The immobilization of Vg on the beads involved coupling an amino group moiety of Vg with the magnetic beads after activation of a carboxylate moiety on the surface of magnetic beads that had been coated with a polylactate film. The Vg-immobilized magnetic beads were introduced and trapped in the immunoreaction cell equipped with the neodymium magnet; a Vg sample solution containing an ALP labeled anti-Vg antibody at a constant concentration and a p-aminophenyl phosphate (PAPP) solution were sequentially introduced into the immunoreaction cell. The product of the enzyme reaction of PAPP with ALP on the antibody, paminophenol, was transported to an amperometric detector, the applied voltage of which was set at +0.2 V vs. an Ag/AgCl reference electrode. A sigmoid calibration curve was obtained when the logarithm of the concentration of Vg was plotted against the peak current of the amperometric detector using various concentrations of standard Vg sample solutions (0-500 ppb). The time required for the analysis is less than 15 min.

Three-body dissociation of OCS3+: Separating sequential and concerted pathways

NASA Astrophysics Data System (ADS)

Kumar, Herendra; Bhatt, Pragya; Safvan, C. P.; Rajput, Jyoti

2018-02-01

Events from the sequential and concerted modes of the fragmentation of OCS3+ that result in coincident detection of fragments C+, O+, and S+ have been separated using a newly proposed representation. An ion beam of 1.8 MeV Xe9+ is used to make the triply charged molecular ion, with the fragments being detected by a recoil ion momentum spectrometer. By separating events belonging exclusively to the sequential mode of breakup, the electronic states of the intermediate molecular ion (CO2+ or CS2+) involved are determined, and from the kinetic energy release spectra, it is shown that the low lying excited states of the parent OCS3+ are responsible for this mechanism. An estimate of branching ratios of events coming from sequential versus concerted mode is presented.

Baking together-the coordination of actions in activities involving people with dementia.

PubMed

Majlesi, Ali Reza; Ekström, Anna

2016-08-01

This study explores interaction and collaboration between people with dementia and their spouses in relation to the performance of household chores with the focus on instruction as an interactional context to engage the person with dementia in collaboration to accomplish joint activities. Dementia is generally associated with pathological changes in people's cognitive functions such as diminishing memory functions, communicative abilities and also diminishing abilities to take initiative as well as to plan and execute tasks. Using video recordings of everyday naturally occurring activities, we analyze the sequential organization of actions (see Schegloff, 2007) oriented toward the accomplishment of a joint multi-task activity of baking. The analysis shows the specific ways of collaboration through instructional activities in which the person with dementia exhibits his competence and skills in accomplishing the given tasks through negotiating the instructions with his partner and carrying out instructed actions. Although the driving force of the collaboration seems to be a series of directive sequences only initiated by the partner throughout the baking activity, our analyses highlight how the person with dementia can actively use the material environment-including collaborating partners-to compensate for challenges and difficulties encountered in achieving everyday tasks. The sequential organization of instructions and instructed actions are in this sense argued to provide an interactional environment wherein the person with dementia can make contributions to the joint activity in an efficient way. While a collaborator has been described as necessary for a person with dementia to be able to partake in activities, this study shows that people with dementia are not only guided by their collaborators in joint activities but they can also actively use their collaborators in intricate compensatory ways. Copyright © 2016 Elsevier Inc. All rights reserved.

Endogenous Sequential Cortical Activity Evoked by Visual Stimuli

PubMed Central

Miller, Jae-eun Kang; Hamm, Jordan P.; Jackson, Jesse; Yuste, Rafael

2015-01-01

Although the functional properties of individual neurons in primary visual cortex have been studied intensely, little is known about how neuronal groups could encode changing visual stimuli using temporal activity patterns. To explore this, we used in vivo two-photon calcium imaging to record the activity of neuronal populations in primary visual cortex of awake mice in the presence and absence of visual stimulation. Multidimensional analysis of the network activity allowed us to identify neuronal ensembles defined as groups of cells firing in synchrony. These synchronous groups of neurons were themselves activated in sequential temporal patterns, which repeated at much higher proportions than chance and were triggered by specific visual stimuli such as natural visual scenes. Interestingly, sequential patterns were also present in recordings of spontaneous activity without any sensory stimulation and were accompanied by precise firing sequences at the single-cell level. Moreover, intrinsic dynamics could be used to predict the occurrence of future neuronal ensembles. Our data demonstrate that visual stimuli recruit similar sequential patterns to the ones observed spontaneously, consistent with the hypothesis that already existing Hebbian cell assemblies firing in predefined temporal sequences could be the microcircuit substrate that encodes visual percepts changing in time. PMID:26063915

Biomimicry Promotes the Efficiency of a 10-Step Sequential Enzymatic Reaction on Nanoparticles, Converting Glucose to Lactate.

PubMed

Mukai, Chinatsu; Gao, Lizeng; Nelson, Jacquelyn L; Lata, James P; Cohen, Roy; Wu, Lauren; Hinchman, Meleana M; Bergkvist, Magnus; Sherwood, Robert W; Zhang, Sheng; Travis, Alexander J

2017-01-02

For nanobiotechnology to achieve its potential, complex organic-inorganic systems must grow to utilize the sequential functions of multiple biological components. Critical challenges exist: immobilizing enzymes can block substrate-binding sites or prohibit conformational changes, substrate composition can interfere with activity, and multistep reactions risk diffusion of intermediates. As a result, the most complex tethered reaction reported involves only 3 enzymes. Inspired by the oriented immobilization of glycolytic enzymes on the fibrous sheath of mammalian sperm, here we show a complex reaction of 10 enzymes tethered to nanoparticles. Although individual enzyme efficiency was higher in solution, the efficacy of the 10-step pathway measured by conversion of glucose to lactate was significantly higher when tethered. To our knowledge, this is the most complex organic-inorganic system described, and it shows that tethered, multi-step biological pathways can be reconstituted in hybrid systems to carry out functions such as energy production or delivery of molecular cargo. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Biomimicry promotes the efficiency of a 10-step sequential enzymatic reaction on nanoparticles, converting glucose to lactate

PubMed Central

Mukai, Chinatsu; Gao, Lizeng; Nelson, Jacquelyn L.; Lata, James P.; Cohen, Roy; Wu, Lauren; Hinchman, Meleana M.; Bergkvist, Magnus; Sherwood, Robert W.; Zhang, Sheng; Travis, Alexander J.

2016-01-01

For nanobiotechnology to achieve its potential, complex organic-inorganic systems must grow to utilize the sequential functions of multiple biological components. Critical challenges exist: immobilizing enzymes can block substrate-binding sites or prohibit conformational changes, substrate composition can interfere with activity, and multistep reactions risk diffusion of intermediates. As a result, the most complex tethered reaction reported involves only 3 enzymes. Inspired by the oriented immobilization of glycolytic enzymes on the fibrous sheath of mammalian sperm, here we show a complex reaction of 10 enzymes tethered to nanoparticles. Although individual enzyme efficiency was higher in solution, the efficacy of the 10-step pathway measured by conversion of glucose to lactate was significantly higher when tethered. To our knowledge, this is the most complex organic-inorganic system described, and it shows that tethered, multi-step biological pathways can be reconstituted in hybrid systems to carry out functions such as energy production or delivery of molecular cargo. PMID:27901298

Molecular Characterization of Macrophage-Biomaterial Interactions

PubMed Central

Moore, Laura Beth; Kyriakides, Themis R.

2015-01-01

Implantation of biomaterials in vascularized tissues elicits the sequential engagement of molecular and cellular elements that constitute the foreign body response. Initial events include the non-specific adsorption of proteins to the biomaterial surface that render it adhesive for cells such as neutrophils and macrophages. The latter undergo unique activation and in some cases undergo cell-cell fusion to form foreign body giant cells that contribute to implant damage and fibrotic encapsulation. In this review, we discuss the molecular events that contribute to macrophage activation and fusion with a focus on the role of the inflammasome, signaling pathways such as JAK/STAT and NF-κB, and the putative involvement of micro RNAs in the regulation of these processes. PMID:26306446

Molecular Characterization of Macrophage-Biomaterial Interactions.

PubMed

Moore, Laura Beth; Kyriakides, Themis R

2015-01-01

Implantation of biomaterials in vascularized tissues elicits the sequential engagement of molecular and cellular elements that constitute the foreign body response. Initial events include the non-specific adsorption of proteins to the biomaterial surface that render it adhesive for cells such as neutrophils and macrophages. The latter undergo unique activation and in some cases undergo cell-cell fusion to form foreign body giant cells that contribute to implant damage and fibrotic encapsulation. In this review, we discuss the molecular events that contribute to macrophage activation and fusion with a focus on the role of the inflammasome, signaling pathways such as JAK/STAT and NF-κB, and the putative involvement of micro RNAs in the regulation of these processes.

Classical and sequential limit analysis revisited

NASA Astrophysics Data System (ADS)

Leblond, Jean-Baptiste; Kondo, Djimédo; Morin, Léo; Remmal, Almahdi

2018-04-01

Classical limit analysis applies to ideal plastic materials, and within a linearized geometrical framework implying small displacements and strains. Sequential limit analysis was proposed as a heuristic extension to materials exhibiting strain hardening, and within a fully general geometrical framework involving large displacements and strains. The purpose of this paper is to study and clearly state the precise conditions permitting such an extension. This is done by comparing the evolution equations of the full elastic-plastic problem, the equations of classical limit analysis, and those of sequential limit analysis. The main conclusion is that, whereas classical limit analysis applies to materials exhibiting elasticity - in the absence of hardening and within a linearized geometrical framework -, sequential limit analysis, to be applicable, strictly prohibits the presence of elasticity - although it tolerates strain hardening and large displacements and strains. For a given mechanical situation, the relevance of sequential limit analysis therefore essentially depends upon the importance of the elastic-plastic coupling in the specific case considered.

The impact of eyewitness identifications from simultaneous and sequential lineups.

PubMed

Wright, Daniel B

2007-10-01

Recent guidelines in the US allow either simultaneous or sequential lineups to be used for eyewitness identification. This paper investigates how potential jurors weight the probative value of the different outcomes from both of these types of lineups. Participants (n=340) were given a description of a case that included some exonerating and some incriminating evidence. There was either a simultaneous or a sequential lineup. Depending on the condition, an eyewitness chose the suspect, chose a filler, or made no identification. The participant had to judge the guilt of the suspect and decide whether to render a guilty verdict. For both simultaneous and sequential lineups an identification had a large effect,increasing the probability of a guilty verdict. There were no reliable effects detected between making no identification and identifying a filler. The effect sizes were similar for simultaneous and sequential lineups. These findings are important for judges and other legal professionals to know for trials involving lineup identifications.

Influence of emotional valence and arousal on the spread of activation in memory.

PubMed

Jhean-Larose, Sandra; Leveau, Nicolas; Denhière, Guy

2014-11-01

Controversy still persists on whether emotional valence and arousal influence cognitive activities. Our study sought to compare how these two factors foster the spread of activation within the semantic network. In a lexical decision task, prime words were varied depending on the valence (pleasant or unpleasant) or on the level of emotional arousal (high or low). Target words were carefully selected to avoid semantic priming effects, as well as to avoid arousing specific emotions (neutral). Three SOA durations (220, 420 and 720 ms) were applied across three independent groups. Results indicate that at 220 ms, the effect of arousal is significantly higher than the effect of valence in facilitating spreading activation while at 420 ms, the effect of valence is significantly higher than the effect of arousal in facilitating spreading activation. These findings suggest that affect is a sequential process involving the successive intervention of arousal and valence.

Sequential avulsions of the tibial tubercle in an adolescent basketball player.

PubMed

Huang, Ying Chieh; Chao, Ying-Hao; Lien, Fang-Chieh

2010-05-01

Tibial tubercle avulsion is an uncommon fracture in physically active adolescents. Sequential avulsion of tibial tubercles is extremely rare. We reported a healthy, active 15-year-old boy who suffered from left tibial tubercle avulsion fracture during a basketball game. He received open reduction and internal fixation with two smooth Kirschner wires and a cannulated screw, with every effort to reduce the plate injury. Long-leg splint was used for protection followed by programmed rehabilitation. He recovered uneventfully and returned to his previous level of activity soon. Another avulsion fracture happened at the right tibial tubercle 3.5 months later when he was playing the basketball. From the encouragement of previous successful treatment, we provided him open reduction and fixation with two small-caliber screws. He recovered uneventfully and returned to his previous level of activity soon. No genu recurvatum or other deformity was happening in our case at the end of 2-year follow-up. No evidence of Osgood-Schlatter disease or osteogenesis imperfecta was found. Sequential avulsion fractures of tibial tubercles are rare. Good functional recovery can often be obtained like our case if we treat it well. To a physically active adolescent, we should never overstate the risk of sequential avulsion of the other leg to postpone the return to an active, functional life.

Nicotinamide N-methyltransferase expression in SH-SY5Y neuroblastoma and N27 mesencephalic neurones induces changes in cell morphology via ephrin-B2 and Akt signalling

PubMed Central

Thomas, M G; Saldanha, M; Mistry, R J; Dexter, D T; Ramsden, D B; Parsons, R B

2013-01-01

Nicotinamide N-methyltransferase (NNMT, E.C. 2.1.1.1) N-methylates nicotinamide to produce 1-methylnicotinamide (MeN). We have previously shown that NNMT expression protected against neurotoxin-mediated cell death by increasing Complex I (CxI) activity, resulting in increased ATP synthesis. This was mediated via protection of the NDUFS3 subunit of CxI from degradation by increased MeN production. In the present study, we have investigated the effects of NNMT expression on neurone morphology and differentiation. Expression of NNMT in SH-SY5Y human neuroblastoma and N27 rat mesencephalic dopaminergic neurones increased neurite branching, synaptophysin expression and dopamine accumulation and release. siRNA gene silencing of ephrin B2 (EFNB2), and inhibition of Akt phosphorylation using LY294002, demonstrated that their sequential activation was responsible for the increases observed. Incubation of SH-SY5Y with increasing concentrations of MeN also increased neurite branching, suggesting that the effects of NNMT may be mediated by MeN. NNMT had no significant effect on the expression of phenotypic and post-mitotic markers, suggesting that NNMT is not involved in determining phenotypic fate or differentiation status. These results demonstrate that NNMT expression regulates neurone morphology in vitro via the sequential activation of the EFNB2 and Akt cellular signalling pathways. PMID:23764850

Nicotinamide N-methyltransferase expression in SH-SY5Y neuroblastoma and N27 mesencephalic neurones induces changes in cell morphology via ephrin-B2 and Akt signalling.

PubMed

Thomas, M G; Saldanha, M; Mistry, R J; Dexter, D T; Ramsden, D B; Parsons, R B

2013-06-13

Nicotinamide N-methyltransferase (NNMT, E.C. 2.1.1.1) N-methylates nicotinamide to produce 1-methylnicotinamide (MeN). We have previously shown that NNMT expression protected against neurotoxin-mediated cell death by increasing Complex I (CxI) activity, resulting in increased ATP synthesis. This was mediated via protection of the NDUFS3 subunit of CxI from degradation by increased MeN production. In the present study, we have investigated the effects of NNMT expression on neurone morphology and differentiation. Expression of NNMT in SH-SY5Y human neuroblastoma and N27 rat mesencephalic dopaminergic neurones increased neurite branching, synaptophysin expression and dopamine accumulation and release. siRNA gene silencing of ephrin B2 (EFNB2), and inhibition of Akt phosphorylation using LY294002, demonstrated that their sequential activation was responsible for the increases observed. Incubation of SH-SY5Y with increasing concentrations of MeN also increased neurite branching, suggesting that the effects of NNMT may be mediated by MeN. NNMT had no significant effect on the expression of phenotypic and post-mitotic markers, suggesting that NNMT is not involved in determining phenotypic fate or differentiation status. These results demonstrate that NNMT expression regulates neurone morphology in vitro via the sequential activation of the EFNB2 and Akt cellular signalling pathways.

The implementation of e-learning tools to enhance undergraduate bioinformatics teaching and learning: a case study in the National University of Singapore

PubMed Central

2009-01-01

Background The rapid advancement of computer and information technology in recent years has resulted in the rise of e-learning technologies to enhance and complement traditional classroom teaching in many fields, including bioinformatics. This paper records the experience of implementing e-learning technology to support problem-based learning (PBL) in the teaching of two undergraduate bioinformatics classes in the National University of Singapore. Results Survey results further established the efficiency and suitability of e-learning tools to supplement PBL in bioinformatics education. 63.16% of year three bioinformatics students showed a positive response regarding the usefulness of the Learning Activity Management System (LAMS) e-learning tool in guiding the learning and discussion process involved in PBL and in enhancing the learning experience by breaking down PBL activities into a sequential workflow. On the other hand, 89.81% of year two bioinformatics students indicated that their revision process was positively impacted with the use of LAMS for guiding the learning process, while 60.19% agreed that the breakdown of activities into a sequential step-by-step workflow by LAMS enhances the learning experience Conclusion We show that e-learning tools are useful for supplementing PBL in bioinformatics education. The results suggest that it is feasible to develop and adopt e-learning tools to supplement a variety of instructional strategies in the future. PMID:19958511

Hospital's activity-based financing system and manager-physician [corrected] interaction.

PubMed

Crainich, David; Leleu, Hervé; Mauleon, Ana

2011-10-01

This paper examines the consequences of the introduction of an activity-based reimbursement system on the behavior of physicians and hospital's managers. We consider a private for-profit sector where both hospitals and physicians are initially paid on a fee-for-service basis. We show that the benefit of the introduction of an activity-based system depends on the type of interaction between managers and physicians (simultaneous or sequential decision-making games). It is shown that, under the activity-based system, a sequential interaction with physician leader could be beneficial for both agents in the private sector. We further model an endogenous timing game à la Hamilton and Slutsky (Games Econ Behav 2: 29-46, 1990) in which the type of interaction is determined endogenously. We show that, under the activity-based system, the sequential interaction with physician leader is the unique subgame perfect equilibrium.

Parsing the Passive: Comparing Children with Specific Language Impairment to Sequential Bilingual Children

ERIC Educational Resources Information Center

Marinis, Theodoros; Saddy, Douglas

2013-01-01

Twenty-five monolingual (L1) children with specific language impairment (SLI), 32 sequential bilingual (L2) children, and 29 L1 controls completed the Test of Active & Passive Sentences-Revised (van der Lely 1996) and the Self-Paced Listening Task with Picture Verification for actives and passives (Marinis 2007). These revealed important…

How Cognitive Styles Affect the Learning Behaviors of Online Problem-Solving Based Discussion Activity: A Lag Sequential Analysis

ERIC Educational Resources Information Center

Wu, Sheng-Yi; Hou, Huei-Tse

2015-01-01

Cognitive styles play an important role in influencing the learning process, but to date no relevant study has been conducted using lag sequential analysis to assess knowledge construction learning patterns based on different cognitive styles in computer-supported collaborative learning activities in online collaborative discussions. This study…

Effects of pretransplant sarcopenia and sequential changes in sarcopenic parameters after living donor liver transplantation.

PubMed

Kaido, Toshimi; Tamai, Yumiko; Hamaguchi, Yuhei; Okumura, Shinya; Kobayashi, Atsushi; Shirai, Hisaya; Yagi, Shintaro; Kamo, Naoko; Hammad, Ahmed; Inagaki, Nobuya; Uemoto, Shinji

2017-01-01

Sarcopenia is characterized by muscle mass depletion and decrease in muscle power or physical activity. We previously reported that low skeletal muscle mass (SMM) is closely involved with posttransplant mortality in patients undergoing living donor liver transplantation (LDLT). The aim of this study was to prospectively investigate the effects of pretransplant sarcopenia on survival and examine sequential changes in sarcopenic parameters after LDLT. Sarcopenia was defined by measuring SMM using a multifrequency body composition analyzer and assessing grip strength (GS) in 72 adults who underwent LDLT at Kyoto University Hospital between January 2013 and October 2015. The effects of pretransplant sarcopenia on short-term survival and sequential changes in SMM and GS were prospectively analyzed. Of 72 patients, 10 (14%) were defined as having pretransplant sarcopenia. Overall survival rates were significantly lower in patients with sarcopenia (n = 10) than those without sarcopenia (n = 62; P < 0.001). SMM worsened after LDLT and did not return to preoperative levels until 1 y after LDLT. In contrast, GS returned to preoperative levels at 6 mo after LDLT, following sharp decrease at 1 mo after LDLT. This prospective study confirmed that pretransplant sarcopenia is closely associated with short-term survival after LDLT and that GS recovers before SMM. Copyright © 2016 Elsevier Inc. All rights reserved.

Sequential allergen desensitization of basophils is non-specific and may involve p38 MAPK.

PubMed

Witting Christensen, S K; Kortekaas Krohn, I; Thuraiaiyah, J; Skjold, T; Schmid, J M; Hoffmann, H J H

2014-10-01

Sequential allergen desensitization provides temporary tolerance for allergic patients. We adapted a clinical protocol to desensitize human blood basophils ex vivo and investigated the mechanism and allergen specificity. We included 28 adult, grass allergic subjects. The optimal, activating allergen concentration was determined by measuring activated CD63(+) CD193(+) SS(Low) basophils in a basophil activation test with 8 log-dilutions of grass allergen. Basophils in whole blood were desensitized by incubation with twofold to 2.5-fold increasing allergen doses in 10 steps starting at 1 : 1000 of the optimal dose. Involvement of p38 mitogen-activated protein kinase (MAPK) was assessed after 3 min of allergen stimulation (n = 7). Allergen specificity was investigated by desensitizing cells from multi-allergic subjects with grass allergen and challenging with optimal doses of grass, birch, recombinant house dust mite (rDer p2) allergen or anti-IgE (n = 10). Desensitization reduced the fraction of blood basophils responding to challenge with an optimal allergen dose from a median (IQR) 81.0% (66.3-88.8) to 35.4% (19.8-47.1, P < 0.0001). CD63 MFI expression was reduced from 68 248 (29 336-92 001) to 30 496 (14 046-46 179, P < 0.0001). Basophils from multi-allergic subjects were desensitized with grass allergen. Challenge with grass allergen resulted in 39.6% activation (15.8-58.3). An unrelated challenge (birch, rDer p2 or anti-IgE) resulted in 53.4% activation (30.8-66.8, P = 0.16 compared with grass). Desensitization reduced p38 MAPK phosphorylation from a median 48.1% (15.6-92.8) to 26.1% (7.4-71.2, P = 0.047) and correlated with decrease in CD63 upregulation (n = 7, r > 0.79, P < 0.05). Desensitization attenuated basophil response rapidly and non-specifically at a stage before p38 MAPK phosphorylation. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

A C–H oxidation approach for streamlining synthesis of chiral polyoxygenated motifs

PubMed Central

Covell, Dustin J.; White, M. Christina

2013-01-01

Chiral oxygenated molecules are pervasive in natural products and medicinal agents; however, their chemical syntheses often necessitate numerous, wasteful steps involving functional group and oxidation state manipulations. Herein a strategy for synthesizing a readily diversifiable class of chiral building blocks, allylic alcohols, through sequential asymmetric C—H activation/resolution is evaluated against the state-of-the-art. The C—H oxidation routes’ capacity to strategically introduce oxygen into a sequence and thereby minimize non-productive manipulations is demonstrated to effect significant decreases in overall step-count and increases in yield and synthetic flexibility. PMID:25013239

Sequential Elution Interactome Analysis of the Mind Bomb 1 Ubiquitin Ligase Reveals a Novel Role in Dendritic Spine Outgrowth*

PubMed Central

Mertz, Joseph; Tan, Haiyan; Pagala, Vishwajeeth; Bai, Bing; Chen, Ping-Chung; Li, Yuxin; Cho, Ji-Hoon; Shaw, Timothy; Wang, Xusheng; Peng, Junmin

2015-01-01

The mind bomb 1 (Mib1) ubiquitin ligase is essential for controlling metazoan development by Notch signaling and possibly the Wnt pathway. It is also expressed in postmitotic neurons and regulates neuronal morphogenesis and synaptic activity by mechanisms that are largely unknown. We sought to comprehensively characterize the Mib1 interactome and study its potential function in neuron development utilizing a novel sequential elution strategy for affinity purification, in which Mib1 binding proteins were eluted under different stringency and then quantified by the isobaric labeling method. The strategy identified the Mib1 interactome with both deep coverage and the ability to distinguish high-affinity partners from low-affinity partners. A total of 817 proteins were identified during the Mib1 affinity purification, including 56 high-affinity partners and 335 low-affinity partners, whereas the remaining 426 proteins are likely copurified contaminants or extremely weak binding proteins. The analysis detected all previously known Mib1-interacting proteins and revealed a large number of novel components involved in Notch and Wnt pathways, endocytosis and vesicle transport, the ubiquitin-proteasome system, cellular morphogenesis, and synaptic activities. Immunofluorescence studies further showed colocalization of Mib1 with five selected proteins: the Usp9x (FAM) deubiquitinating enzyme, alpha-, beta-, and delta-catenins, and CDKL5. Mutations of CDKL5 are associated with early infantile epileptic encephalopathy-2 (EIEE2), a severe form of mental retardation. We found that the expression of Mib1 down-regulated the protein level of CDKL5 by ubiquitination, and antagonized CDKL5 function during the formation of dendritic spines. Thus, the sequential elution strategy enables biochemical characterization of protein interactomes; and Mib1 analysis provides a comprehensive interactome for investigating its role in signaling networks and neuronal development. PMID:25931508

An N-terminal di-proline motif is essential for fatty acid–dependent degradation of Δ9-desaturase in Drosophila

PubMed Central

Murakami, Akira; Nagao, Kohjiro; Juni, Naoto; Hara, Yuji; Umeda, Masato

2017-01-01

The Δ9-fatty acid desaturase introduces a double bond at the Δ9 position of the acyl moiety of acyl-CoA and regulates the cellular levels of unsaturated fatty acids. However, it is unclear how Δ9-desaturase expression is regulated in response to changes in the levels of fatty acid desaturation. In this study, we found that the degradation of DESAT1, the sole Δ9-desaturase in the Drosophila cell line S2, was significantly enhanced when the amounts of unsaturated acyl chains of membrane phospholipids were increased by supplementation with unsaturated fatty acids, such as oleic and linoleic acids. In contrast, inhibition of DESAT1 activity remarkably suppressed its degradation. Of note, removal of the DESAT1 N-terminal domain abolished the responsiveness of DESAT1 degradation to the level of fatty acid unsaturation. Further truncation and amino acid replacement analyses revealed that two sequential prolines, the second and third residues of DESAT1, were responsible for the unsaturated fatty acid–dependent degradation. Although degradation of mouse stearoyl-CoA desaturase 1 (SCD1) was unaffected by changes in fatty acid unsaturation, introduction of the N-terminal sequential proline residues into SCD1 conferred responsiveness to unsaturated fatty acid–dependent degradation. Furthermore, we also found that the Ca2+-dependent cysteine protease calpain is involved in the sequential proline–dependent degradation of DESAT1. In light of these findings, we designated the sequential prolines at the second and third positions of DESAT1 as a “di-proline motif,” which plays a crucial role in the regulation of Δ9-desaturase expression in response to changes in the level of cellular unsaturated fatty acids. PMID:28972163

Transformation of Cortex-wide Emergent Properties during Motor Learning.

PubMed

Makino, Hiroshi; Ren, Chi; Liu, Haixin; Kim, An Na; Kondapaneni, Neehar; Liu, Xin; Kuzum, Duygu; Komiyama, Takaki

2017-05-17

Learning involves a transformation of brain-wide operation dynamics. However, our understanding of learning-related changes in macroscopic dynamics is limited. Here, we monitored cortex-wide activity of the mouse brain using wide-field calcium imaging while the mouse learned a motor task over weeks. Over learning, the sequential activity across cortical modules became temporally more compressed, and its trial-by-trial variability decreased. Moreover, a new flow of activity emerged during learning, originating from premotor cortex (M2), and M2 became predictive of the activity of many other modules. Inactivation experiments showed that M2 is critical for the post-learning dynamics in the cortex-wide activity. Furthermore, two-photon calcium imaging revealed that M2 ensemble activity also showed earlier activity onset and reduced variability with learning, which was accompanied by changes in the activity-movement relationship. These results reveal newly emergent properties of macroscopic cortical dynamics during motor learning and highlight the importance of M2 in controlling learned movements. Copyright © 2017 Elsevier Inc. All rights reserved.

Sequential neural processes in abacus mental addition: an EEG and FMRI case study.

PubMed

Ku, Yixuan; Hong, Bo; Zhou, Wenjing; Bodner, Mark; Zhou, Yong-Di

2012-01-01

Abacus experts are able to mentally calculate multi-digit numbers rapidly. Some behavioral and neuroimaging studies have suggested a visuospatial and visuomotor strategy during abacus mental calculation. However, no study up to now has attempted to dissociate temporally the visuospatial neural process from the visuomotor neural process during abacus mental calculation. In the present study, an abacus expert performed the mental addition tasks (8-digit and 4-digit addends presented in visual or auditory modes) swiftly and accurately. The 100% correct rates in this expert's task performance were significantly higher than those of ordinary subjects performing 1-digit and 2-digit addition tasks. ERPs, EEG source localizations, and fMRI results taken together suggested visuospatial and visuomotor processes were sequentially arranged during the abacus mental addition with visual addends and could be dissociated from each other temporally. The visuospatial transformation of the numbers, in which the superior parietal lobule was most likely involved, might occur first (around 380 ms) after the onset of the stimuli. The visuomotor processing, in which the superior/middle frontal gyri were most likely involved, might occur later (around 440 ms). Meanwhile, fMRI results suggested that neural networks involved in the abacus mental addition with auditory stimuli were similar to those in the visual abacus mental addition. The most prominently activated brain areas in both conditions included the bilateral superior parietal lobules (BA 7) and bilateral middle frontal gyri (BA 6). These results suggest a supra-modal brain network in abacus mental addition, which may develop from normal mental calculation networks.

Involving young people in decision making about sequential cochlear implantation.

PubMed

Ion, Rebecca; Cropper, Jenny; Walters, Hazel

2013-11-01

The National Institute for Health and Clinical Excellence guidelines recommended young people who currently have one cochlear implant be offered assessment for a second, sequential implant, due to the reported improvements in sound localization and speech perception in noise. The possibility and benefits of group information and counselling assessments were considered. Previous research has shown advantages of group sessions involving young people and their families and such groups which also allow young people opportunity to discuss their concerns separately to their parents/guardians are found to be 'hugely important'. Such research highlights the importance of involving children in decision-making processes. Families considering a sequential cochlear implant were invited to a group information/counselling session, which included time for parents and children to meet separately. Fourteen groups were held with approximately four to five families in each session, totalling 62 patients. The sessions were facilitated by the multi-disciplinary team, with a particular psychological focus in the young people's session. Feedback from families has demonstrated positive support for this format. Questionnaire feedback, to which nine families responded, indicated that seven preferred the group session to an individual session and all approved of separate groups for the child and parents/guardians. Overall the group format and psychological focus were well received in this typically surgical setting and emphasized the importance of involving the young person in the decision-making process. This positive feedback also opens up the opportunity to use a group format in other assessment processes.

Motor Timing Deficits in Sequential Movements in Parkinson Disease Are Related to Action Planning: A Motor Imagery Study

PubMed Central

Avanzino, Laura; Pelosin, Elisa; Martino, Davide; Abbruzzese, Giovanni

2013-01-01

Timing of sequential movements is altered in Parkinson disease (PD). Whether timing deficits in internally generated sequential movements in PD depends also on difficulties in motor planning, rather than merely on a defective ability to materially perform the planned movement is still undefined. To unveil this issue, we adopted a modified version of an established test for motor timing, i.e. the synchronization–continuation paradigm, by introducing a motor imagery task. Motor imagery is thought to involve mainly processes of movement preparation, with reduced involvement of end-stage movement execution-related processes. Fourteen patients with PD and twelve matched healthy volunteers were asked to tap in synchrony with a metronome cue (SYNC) and then, when the tone stopped, to keep tapping, trying to maintain the same rhythm (CONT-EXE) or to imagine tapping at the same rhythm, rather than actually performing it (CONT-MI). We tested both a sub-second and a supra-second inter-stimulus interval between the cues. Performance was recorded using a sensor-engineered glove and analyzed measuring the temporal error and the interval reproduction accuracy index. PD patients were less accurate than healthy subjects in the supra-second time reproduction task when performing both continuation tasks (CONT-MI and CONT-EXE), whereas no difference was detected in the synchronization task and on all tasks involving a sub-second interval. Our findings suggest that PD patients exhibit a selective deficit in motor timing for sequential movements that are separated by a supra-second interval and that this deficit may be explained by a defect of motor planning. Further, we propose that difficulties in motor planning are of a sufficient degree of severity in PD to affect also the motor performance in the supra-second time reproduction task. PMID:24086534

Learning multiple variable-speed sequences in striatum via cortical tutoring.

PubMed

Murray, James M; Escola, G Sean

2017-05-08

Sparse, sequential patterns of neural activity have been observed in numerous brain areas during timekeeping and motor sequence tasks. Inspired by such observations, we construct a model of the striatum, an all-inhibitory circuit where sequential activity patterns are prominent, addressing the following key challenges: (i) obtaining control over temporal rescaling of the sequence speed, with the ability to generalize to new speeds; (ii) facilitating flexible expression of distinct sequences via selective activation, concatenation, and recycling of specific subsequences; and (iii) enabling the biologically plausible learning of sequences, consistent with the decoupling of learning and execution suggested by lesion studies showing that cortical circuits are necessary for learning, but that subcortical circuits are sufficient to drive learned behaviors. The same mechanisms that we describe can also be applied to circuits with both excitatory and inhibitory populations, and hence may underlie general features of sequential neural activity pattern generation in the brain.

Stage-specific effects of Notch activation during skeletal myogenesis

PubMed Central

Bi, Pengpeng; Yue, Feng; Sato, Yusuke; Wirbisky, Sara; Liu, Weiyi; Shan, Tizhong; Wen, Yefei; Zhou, Daoguo; Freeman, Jennifer; Kuang, Shihuan

2016-01-01

Skeletal myogenesis involves sequential activation, proliferation, self-renewal/differentiation and fusion of myogenic stem cells (satellite cells). Notch signaling is known to be essential for the maintenance of satellite cells, but its function in late-stage myogenesis, i.e. post-differentiation myocytes and post-fusion myotubes, is unknown. Using stage-specific Cre alleles, we uncovered distinct roles of Notch1 in mononucleated myocytes and multinucleated myotubes. Specifically, constitutive Notch1 activation dedifferentiates myocytes into Pax7 quiescent satellite cells, leading to severe defects in muscle growth and regeneration, and postnatal lethality. By contrast, myotube-specific Notch1 activation improves the regeneration and exercise performance of aged and dystrophic muscles. Mechanistically, Notch1 activation in myotubes upregulates the expression of Notch ligands, which modulate Notch signaling in the adjacent satellite cells to enhance their regenerative capacity. These results highlight context-dependent effects of Notch activation during myogenesis, and demonstrate that Notch1 activity improves myotube’s function as a stem cell niche. DOI: http://dx.doi.org/10.7554/eLife.17355.001 PMID:27644105

The Intelligent Management System: An Overview.

DTIC Science & Technology

1982-12-07

comprises of hundreds of subprocesses concerned with bulb grasping, positioning, heating, cooling, etc. Each is sequentially related with others in time...activity. Activity schemata can be constructed into a network to define both parallel and sequential precedence, and hierarchical to describe...The flow of work is controlled by the "operation- lineup " associated with the product being manufactured. The operation- lineup specifies the sequence of

Hemispheric asymmetry in the hierarchical perception of music and speech.

PubMed

Rosenthal, Matthew A

2016-11-01

The perception of music and speech involves a higher level, cognitive mechanism that allows listeners to form expectations for future music and speech events. This article comprehensively reviews studies on hemispheric differences in the formation of melodic and harmonic expectations in music and selectively reviews studies on hemispheric differences in the formation of syntactic and semantic expectations in speech. On the basis of this review, it is concluded that the higher level mechanism flexibly lateralizes music processing to either hemisphere depending on the expectation generated by a given musical context. When a context generates in the listener an expectation whose elements are sequentially ordered over time, higher level processing is dominant in the left hemisphere. When a context generates in the listener an expectation whose elements are not sequentially ordered over time, higher level processing is dominant in the right hemisphere. This article concludes with a spreading activation model that describes expectations for music and speech in terms of shared temporal and nontemporal representations. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Sequential stages and distribution patterns of aging-related tau astrogliopathy (ARTAG) in the human brain.

PubMed

Kovacs, Gabor G; Xie, Sharon X; Robinson, John L; Lee, Edward B; Smith, Douglas H; Schuck, Theresa; Lee, Virginia M-Y; Trojanowski, John Q

2018-06-11

Aging-related tau astrogliopathy (ARTAG) describes tau pathology in astrocytes in different locations and anatomical regions. In the present study we addressed the question of whether sequential distribution patterns can be recognized for ARTAG or astroglial tau pathologies in both primary FTLD-tauopathies and non-FTLD-tauopathy cases. By evaluating 687 postmortem brains with diverse disorders we identified ARTAG in 455. We evaluated frequencies and hierarchical clustering of anatomical involvement and used conditional probability and logistic regression to model the sequential distribution of ARTAG and astroglial tau pathologies across different brain regions. For subpial and white matter ARTAG we recognize three and two patterns, respectively, each with three stages initiated or ending in the amygdala. Subependymal ARTAG does not show a clear sequential pattern. For grey matter (GM) ARTAG we recognize four stages including a striatal pathway of spreading towards the cortex and/or amygdala, and the brainstem, and an amygdala pathway, which precedes the involvement of the striatum and/or cortex and proceeds towards the brainstem. GM ARTAG and astrocytic plaque pathology in corticobasal degeneration follows a predominantly frontal-parietal cortical to temporal-occipital cortical, to subcortical, to brainstem pathway (four stages). GM ARTAG and tufted astrocyte pathology in progressive supranuclear palsy shows a striatum to frontal-parietal cortical to temporal to occipital, to amygdala, and to brainstem sequence (four stages). In Pick's disease cases with astroglial tau pathology an overlapping pattern with PSP can be appreciated. We conclude that tau-astrogliopathy type-specific sequential patterns cannot be simplified as neuron-based staging systems. The proposed cytopathological and hierarchical stages provide a conceptual approach to identify the initial steps of the pathogenesis of tau pathologies in ARTAG and primary FTLD-tauopathies.

A Simulation Approach to Assessing Sampling Strategies for Insect Pests: An Example with the Balsam Gall Midge

PubMed Central

Carleton, R. Drew; Heard, Stephen B.; Silk, Peter J.

2013-01-01

Estimation of pest density is a basic requirement for integrated pest management in agriculture and forestry, and efficiency in density estimation is a common goal. Sequential sampling techniques promise efficient sampling, but their application can involve cumbersome mathematics and/or intensive warm-up sampling when pests have complex within- or between-site distributions. We provide tools for assessing the efficiency of sequential sampling and of alternative, simpler sampling plans, using computer simulation with “pre-sampling” data. We illustrate our approach using data for balsam gall midge (Paradiplosis tumifex) attack in Christmas tree farms. Paradiplosis tumifex proved recalcitrant to sequential sampling techniques. Midge distributions could not be fit by a common negative binomial distribution across sites. Local parameterization, using warm-up samples to estimate the clumping parameter k for each site, performed poorly: k estimates were unreliable even for samples of n∼100 trees. These methods were further confounded by significant within-site spatial autocorrelation. Much simpler sampling schemes, involving random or belt-transect sampling to preset sample sizes, were effective and efficient for P. tumifex. Sampling via belt transects (through the longest dimension of a stand) was the most efficient, with sample means converging on true mean density for sample sizes of n∼25–40 trees. Pre-sampling and simulation techniques provide a simple method for assessing sampling strategies for estimating insect infestation. We suspect that many pests will resemble P. tumifex in challenging the assumptions of sequential sampling methods. Our software will allow practitioners to optimize sampling strategies before they are brought to real-world applications, while potentially avoiding the need for the cumbersome calculations required for sequential sampling methods. PMID:24376556

Observer Training Revisited: A Comparison of in Vivo and Video Instruction

ERIC Educational Resources Information Center

Dempsey, Carrie M.; Iwata, Brian A.; Fritz, Jennifer N.; Rolider, Natalie U.

2012-01-01

We compared the effects of 2 observer-training procedures. In vivo training involved practice during actual treatment sessions. Video training involved practice while watching progressively more complex simulations. Fifty-nine undergraduate students entered 1 of the 2 training conditions sequentially according to an ABABAB design. Results showed…

Dizocilpine (MK-801) impairs learning in the active place avoidance task but has no effect on the performance during task/context alternation.

PubMed

Vojtechova, Iveta; Petrasek, Tomas; Hatalova, Hana; Pistikova, Adela; Vales, Karel; Stuchlik, Ales

2016-05-15

The prevention of engram interference, pattern separation, flexibility, cognitive coordination and spatial navigation are usually studied separately at the behavioral level. Impairment in executive functions is often observed in patients suffering from schizophrenia. We have designed a protocol for assessing these functions all together as behavioral separation. This protocol is based on alternated or sequential training in two tasks testing different hippocampal functions (the Morris water maze and active place avoidance), and alternated or sequential training in two similar environments of the active place avoidance task. In Experiment 1, we tested, in adult rats, whether the performance in two different spatial tasks was affected by their order in sequential learning, or by their day-to-day alternation. In Experiment 2, rats learned to solve the active place avoidance task in two environments either alternately or sequentially. We found that rats are able to acquire both tasks and to discriminate both similar contexts without obvious problems regardless of the order or the alternation. We used two groups of rats, controls and a rat model of psychosis induced by a subchronic intraperitoneal application of 0.08mg/kg of dizocilpine (MK-801), a non-competitive antagonist of NMDA receptors. Dizocilpine had no selective effect on parallel/sequential learning of tasks/contexts. However, it caused hyperlocomotion and a significant deficit in learning in the active place avoidance task regardless of the task alternation. Cognitive coordination tested by this task is probably more sensitive to dizocilpine than spatial orientation because no hyperactivity or learning impairment was observed in the Morris water maze. Copyright © 2016 Elsevier B.V. All rights reserved.

Dynamics of Sequential Decision Making

NASA Astrophysics Data System (ADS)

Rabinovich, Mikhail I.; Huerta, Ramón; Afraimovich, Valentin

2006-11-01

We suggest a new paradigm for intelligent decision-making suitable for dynamical sequential activity of animals or artificial autonomous devices that depends on the characteristics of the internal and external world. To do it we introduce a new class of dynamical models that are described by ordinary differential equations with a finite number of possibilities at the decision points, and also include rules solving this uncertainty. Our approach is based on the competition between possible cognitive states using their stable transient dynamics. The model controls the order of choosing successive steps of a sequential activity according to the environment and decision-making criteria. Two strategies (high-risk and risk-aversion conditions) that move the system out of an erratic environment are analyzed.

IL-1β-induced, matrix metalloproteinase-3-regulated proliferation of embryonic stem cell-derived odontoblastic cells is mediated by the Wnt5 signaling pathway

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

Ozeki, Nobuaki; Hase, Naoko; Hiyama, Taiki

2014-10-15

We previously established a method for differentiating induced pluripotent stem cells and embryonic stem (ES) cells into α2 integrin-positive odontoblast-like cells. We also reported that interleukin (IL)-1β induces matrix metalloproteinase (MMP)-3-regulated cell proliferation and suppresses apoptosis in these cells, suggesting that MMP-3 plays a potentially unique physiological role in the regeneration of odontoblast-like cells. Here, we examined whether up-regulation of MMP-3 activity by IL-1β was mediated by Wnt signaling and led to increased proliferation of odontoblast-like cells. IL-1β increased mRNA and protein levels of Wnt5a, Wnt5b and the Wnt receptor Lrp5. Exogenous Wnt5a and Wnt5b were found to increase MMP-3more » mRNA, protein and activity, and interestingly the rate of proliferation in these cells. Treatment with siRNAs against Wnt5a, Wnt5b and Lrp5 suppressed the IL-1β-induced increase in MMP-3 expression and suppressed cell proliferation, an effect rescued by application of exogenous Wnt5. These results demonstrate the sequential involvement of Wnt5, Lrp5 and MMP-3 in effecting IL-1β-induced proliferation of ES cell-derived odontoblast-like cells. - Highlights: • IL-1β induces Wnt5, Lrp5/Fzd9 and MMP-3 in ES cell-derived odontoblast-like cells. • IL-1β-induced Wnt5 expression results in increased cell proliferation. • Exogenous Wnt5 increases MMP-3 activity and cell proliferation. • Exogenous Wnt5 rescues IL-1β-driven proliferation with anti-Wnt5 siRNA suppression. • IL-1β-induced cell proliferation involves Wnt5, Lrp5, and MMP-3 sequentially.« less

The Obstacles for the Teaching of 8th Grade TR History of Revolution and Kemalism Course According to the Constructivist Approach (An Example of Exploratory Sequential Mixed Method Design)

ERIC Educational Resources Information Center

Karademir, Yavuz; Demir, Selcuk Besir

2015-01-01

The aim of this study is to ascertain the problems social studies teachers face in the teaching of topics covered in 8th grade TRHRK Course. The study was conducted in line with explanatory sequential mixed method design, which is one of the mixed research method, was used. The study involves three phases. In the first step, exploratory process…

Automated single-slide staining device

NASA Technical Reports Server (NTRS)

Wilkins, J. R.; Mills, S. M. (Inventor)

1977-01-01

A simple apparatus and method is disclosed for making individual single Gram stains on bacteria inoculated slides to assist in classifying bacteria in the laboratory as Gram-positive or Gram-negative. The apparatus involves positioning a single inoculated slide in a stationary position and thereafter automatically and sequentially flooding the slide with increments of a primary stain, a mordant, a decolorizer, a counterstain and a wash solution in a sequential manner without the individual lab technician touching the slide and with minimum danger of contamination thereof from other slides.

Sequential Reactions of Surface-Tethered Glycolytic Enzymes

PubMed Central

Mukai, Chinatsu; Bergkvist, Magnus; Nelson, Jacquelyn L.; Travis, Alexander J.

2014-01-01

SUMMARY The development of complex hybrid organic-inorganic devices faces several challenges, including how they can generate energy. Cells face similar challenges regarding local energy production. Mammalian sperm solve this problem by generating ATP down the flagellar principal piece by means of glycolytic enzymes, several of which are tethered to a cytoskeletal support via germ cell-specific targeting domains. Inspired by this design, we have produced recombinant hexokinase type 1 and glucose-6-phosphate isomerase capable of oriented immobilization on a nickel-nitrilotriacetic acid modified surface. Specific activities of enzymes tethered via this strategy were substantially higher than when randomly adsorbed. Furthermore, these enzymes showed sequential activities when tethered onto the same surface. This is the first demonstration of surface-tethered pathway components showing sequential enzymatic activities, and it provides a first step toward reconstitution of glycolysis on engineered hybrid devices. PMID:19778729

Characteristics of sequential swallowing of liquids in young and elderly adults: an integrative review.

PubMed

Veiga, Helena Perrut; Bianchini, Esther Mandelbaum Gonçalves

2012-01-01

To perform an integrative review of studies on liquid sequential swallowing, by characterizing the methodology of the studies and the most important findings in young and elderly adults. Review of the literature written in English and Portuguese on PubMed, LILACS, SciELO and MEDLINE databases, within the past twenty years, available fully, using the following uniterms: sequential swallowing, swallowing, dysphagia, cup, straw, in various combinations. Research articles with a methodological approach on the characterization of liquid sequential swallowing by young and/or elderly adults, regardless of health condition, excluding studies involving only the esophageal phase. The following research indicators were applied: objectives, number and gender of participants; age group; amount of liquid offered; intake instruction; utensil used, methods and main findings. 18 studies met the established criteria. The articles were categorized according to the sample characterization and the methodology on volume intake, utensil used and types of exams. Most studies investigated only healthy individuals, with no swallowing complaints. Subjects were given different instructions as to the intake of all the volume: usual manner, continually, as rapidly as possible. The findings about the characterization of sequential swallowing were varied and described in accordance with the objectives of each study. It found great variability in the methodology employed to characterize the sequential swallowing. Some findings are not comparable, and sequential swallowing is not studied in most swallowing protocols, without consensus on the influence of the utensil.

Nanoparticle bioconjugates as "bottom-up" assemblies of artifical multienzyme complexes

NASA Astrophysics Data System (ADS)

Keighron, Jacqueline D.

2010-11-01

The sequential enzymes of several metabolic pathways have been shown to exist in close proximity with each other in the living cell. Although not proven in all cases, colocalization may have several implications for the rate of metabolite formation. Proximity between the sequential enzymes of a metabolic pathway has been proposed to have several benefits for the overall rate of metabolite formation. These include reduced diffusion distance for intermediates, sequestering of intermediates from competing pathways and the cytoplasm. Restricted diffusion in the vicinity of an enzyme can also cause the pooling of metabolites, which can alter reaction equilibria to control the rate of reaction through inhibition. Associations of metabolic enzymes are difficult to isolate ex vivo due to the weak interactions believed to colocalize sequential enzymes within the cell. Therefore model systems in which the proximity and diffusion of intermediates within the experiment system are controlled are attractive alternatives to explore the effects of colocalization of sequential enzymes. To this end three model systems for multienzyme complexes have been constructed. Direct adsorption enzyme:gold nanoparticle bioconjugates functionalized with malate dehydrogenase (MDH) and citrate synthase (CS) allow for proximity between to the enzymes to be controlled from the nanometer to micron range. Results show that while the enzymes present in the colocalized and non-colocalized systems compared here behaved differently overall the sequential activity of the pathway was improved by (1) decreasing the diffusion distance between active sites, (2) decreasing the diffusion coefficient of the reaction intermediate to prevent escape into the bulk solution, and (3) decreasing the overall amount of bioconjugate in the solution to prevent the pathway from being inhibited by the buildup of metabolite over time. Layer-by-layer (LBL) assemblies of MDH and CS were used to examine the layering effect of sequential enzymes found in multienzyme complexes such as the pyruvate dehydrogenase complex (PDC). By controlling the orientation of enzymes in the complex (i.e. how deeply embedded each enzyme is) it was hypothesized that differences in sequential activity would determine an optimal orientation for a multienzyme complex. It was determined during the course of these experiments that the polyelectrolyte (PE) assembly itself served to slow diffusion of intermediates, leading to a buildup of oxaloacetate within the PE layers to form a pool of metabolite that equalized the rate of sequential reaction between the different orientations tested. Hexahistidine tag -- Ni(II) nitriliotriacetic acid (NTA) chemistry is an attractive method to control the proximity between sequential enzymes because each enzyme can be bound in a specific orientation, with minimal loss of activity, and the interaction is reversible. Modifying gold nanoparticles or large unilamellar vesicles with this functionality allows for another class of model to be constructed in which proximity between enzymes is dynamic. Some metabolic pathways (such as the de novo purine biosynthetic pathway), have demonstrated dynamic proximity of sequential enzymes in response to specific cellular stimuli. Results indicate that Ni(II)NTA scaffolds immobilize histidine-tagged enzymes non-destructively, with a near 100% reversibility. This model can be used to demonstrate the possible implications of dynamic proximity such as pathway regulation. Insight into the benefits and mechanisms of sequential enzyme colocalization can enhance the general understanding of cellular processes, as well as allow for the development of new and innovative ways to modulate pathway activity. This may provide new designs for treatments of metabolic diseases and cancer, where metabolic pathways are altered.

Accelerated drug release and clearance of PEGylated epirubicin liposomes following repeated injections: a new challenge for sequential low-dose chemotherapy

PubMed Central

Yang, Qiang; Ma, Yanling; Zhao, Yongxue; She, Zhennan; Wang, Long; Li, Jie; Wang, Chunling; Deng, Yihui

2013-01-01

Background Sequential low-dose chemotherapy has received great attention for its unique advantages in attenuating multidrug resistance of tumor cells. Nevertheless, it runs the risk of producing new problems associated with the accelerated blood clearance phenomenon, especially with multiple injections of PEGylated liposomes. Methods Liposomes were labeled with fluorescent phospholipids of 1,2-dipalmitoyl-snglycero-3-phosphoethanolamine-N-(7-nitro-2-1,3-benzoxadiazol-4-yl) and epirubicin (EPI). The pharmacokinetics profile and biodistribution of the drug and liposome carrier following multiple injections were determined. Meanwhile, the antitumor effect of sequential low-dose chemotherapy was tested. To clarify this unexpected phenomenon, the production of polyethylene glycol (PEG)-specific immunoglobulin M (IgM), drug release, and residual complement activity experiments were conducted in serum. Results The first or sequential injections of PEGylated liposomes within a certain dose range induced the rapid clearance of subsequently injected PEGylated liposomal EPI. Of note, the clearance of EPI was two- to three-fold faster than the liposome itself, and a large amount of EPI was released from liposomes in the first 30 minutes in a complement-activation, direct-dependent manner. The therapeutic efficacy of liposomal EPI following 10 days of sequential injections in S180 tumor-bearing mice of 0.75 mg EPI/kg body weight was almost completely abolished between the sixth and tenth day of the sequential injections, even although the subsequently injected doses were doubled. The level of PEG-specific IgM in the blood increased rapidly, with a larger amount of complement being activated while the concentration of EPI in blood and tumor tissue was significantly reduced. Conclusion Our investigation implied that the accelerated blood clearance phenomenon and its accompanying rapid leakage and clearance of drug following sequential low-dose injections may reverse the unique pharmacokinetic–toxicity profile of liposomes which deserved our attention. Therefore, a more reasonable treatment regime should be selected to lessen or even eliminate this phenomenon. PMID:23576868

A fast and accurate online sequential learning algorithm for feedforward networks.

PubMed

Liang, Nan-Ying; Huang, Guang-Bin; Saratchandran, P; Sundararajan, N

2006-11-01

In this paper, we develop an online sequential learning algorithm for single hidden layer feedforward networks (SLFNs) with additive or radial basis function (RBF) hidden nodes in a unified framework. The algorithm is referred to as online sequential extreme learning machine (OS-ELM) and can learn data one-by-one or chunk-by-chunk (a block of data) with fixed or varying chunk size. The activation functions for additive nodes in OS-ELM can be any bounded nonconstant piecewise continuous functions and the activation functions for RBF nodes can be any integrable piecewise continuous functions. In OS-ELM, the parameters of hidden nodes (the input weights and biases of additive nodes or the centers and impact factors of RBF nodes) are randomly selected and the output weights are analytically determined based on the sequentially arriving data. The algorithm uses the ideas of ELM of Huang et al. developed for batch learning which has been shown to be extremely fast with generalization performance better than other batch training methods. Apart from selecting the number of hidden nodes, no other control parameters have to be manually chosen. Detailed performance comparison of OS-ELM is done with other popular sequential learning algorithms on benchmark problems drawn from the regression, classification and time series prediction areas. The results show that the OS-ELM is faster than the other sequential algorithms and produces better generalization performance.

On the origin of reproducible sequential activity in neural circuits

NASA Astrophysics Data System (ADS)

Afraimovich, V. S.; Zhigulin, V. P.; Rabinovich, M. I.

2004-12-01

Robustness and reproducibility of sequential spatio-temporal responses is an essential feature of many neural circuits in sensory and motor systems of animals. The most common mathematical images of dynamical regimes in neural systems are fixed points, limit cycles, chaotic attractors, and continuous attractors (attractive manifolds of neutrally stable fixed points). These are not suitable for the description of reproducible transient sequential neural dynamics. In this paper we present the concept of a stable heteroclinic sequence (SHS), which is not an attractor. SHS opens the way for understanding and modeling of transient sequential activity in neural circuits. We show that this new mathematical object can be used to describe robust and reproducible sequential neural dynamics. Using the framework of a generalized high-dimensional Lotka-Volterra model, that describes the dynamics of firing rates in an inhibitory network, we present analytical results on the existence of the SHS in the phase space of the network. With the help of numerical simulations we confirm its robustness in presence of noise in spite of the transient nature of the corresponding trajectories. Finally, by referring to several recent neurobiological experiments, we discuss possible applications of this new concept to several problems in neuroscience.

On the origin of reproducible sequential activity in neural circuits.

PubMed

Afraimovich, V S; Zhigulin, V P; Rabinovich, M I

2004-12-01

Robustness and reproducibility of sequential spatio-temporal responses is an essential feature of many neural circuits in sensory and motor systems of animals. The most common mathematical images of dynamical regimes in neural systems are fixed points, limit cycles, chaotic attractors, and continuous attractors (attractive manifolds of neutrally stable fixed points). These are not suitable for the description of reproducible transient sequential neural dynamics. In this paper we present the concept of a stable heteroclinic sequence (SHS), which is not an attractor. SHS opens the way for understanding and modeling of transient sequential activity in neural circuits. We show that this new mathematical object can be used to describe robust and reproducible sequential neural dynamics. Using the framework of a generalized high-dimensional Lotka-Volterra model, that describes the dynamics of firing rates in an inhibitory network, we present analytical results on the existence of the SHS in the phase space of the network. With the help of numerical simulations we confirm its robustness in presence of noise in spite of the transient nature of the corresponding trajectories. Finally, by referring to several recent neurobiological experiments, we discuss possible applications of this new concept to several problems in neuroscience.

Concise Syntheses of bis-Strychnos Alkaloids (-)-Sungucine, (-)-Isosungucine, and (-)-Strychnogucine B from (-)-Strychnine.

PubMed

Zhao, Senzhi; Teijaro, Christiana N; Chen, Heng; Sirasani, Gopal; Vaddypally, Shivaiah; Zdilla, Michael J; Dobereiner, Graham E; Andrade, Rodrigo B

2016-08-08

The first chemical syntheses of complex, bis-Strychnos alkaloids (-)-sungucine (1), (-)-isosungucine (2), and (-)-strychnogucine B (3) from (-)-strychnine (4) is reported. Key steps included (1) the Polonovski-Potier activation of strychnine N-oxide; (2) a biomimetic Mannich coupling to forge the signature C23-C5' bond that joins two monoterpene indole monomers; and (3) a sequential HBr/NaBH3 CN-mediated reduction to fashion the ethylidene moieties in 1-3. DFT calculations were employed to rationalize the regiochemical course of reactions involving strychnine congeners. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Introductory comments on the USGS geographic applications program

NASA Technical Reports Server (NTRS)

Gerlach, A. C.

1970-01-01

The third phase of remote sensing technologies and potentials applied to the operations of the U.S. Geological Survey is introduced. Remote sensing data with multidisciplinary spatial data from traditional sources is combined with geographic theory and techniques of environmental modeling. These combined imputs are subject to four sequential activities that involve: (1) thermatic mapping of land use and environmental factors; (2) the dynamics of change detection; (3) environmental surveillance to identify sudden changes and general trends; and (4) preparation of statistical model and analytical reports. Geography program functions, products, clients, and goals are presented in graphical form, along with aircraft photo missions, geography test sites, and FY-70.

Simultaneous, But Not Consecutive, Combination With Folinate Salts Potentiates 5-Fluorouracil Antitumor Activity In Vitro and In Vivo.

PubMed

Di Paolo, Antonello; Orlandi, Paola; Di Desidero, Teresa; Danesi, Romano; Bocci, Guido

2017-08-07

The combination of folinate salts to 5-fluoruracil (5-FU)-based schedules is an established clinical routine in the landscape of colorectal cancer treatment. The aim of this study was to investigate the pharmacological differences between the sequential administration of folinate salts (1 h before, as in clinical routine) followed by 5-FU and the simultaneous administration of both drugs. Proliferation and apoptotic assays were performed on human colon cancer cells exposed to 5-FU, calcium (CaLV), or disodium (NaLV) levofolinate or their simultaneous and sequential combination for 24 and 72 h. TYMS and SLC19A1 gene expression was performed with real-time PCR. In vivo experiments were performed in xenografted nude mice, which were treated with 5-FU escalating doses and CaLV or NaLV alone or in simultaneous and sequential combination. The simultaneous combination of folinate salts and 5-FU was synergistic (NaLV) or additive (CaLV) in a 24-h treatment in both cell lines. In contrast, the sequential combination of both folinate salts and 5-FU was antagonistic at 24 and 72 h. The simultaneous combination of 5-FU and NaLV or CaLV inhibited TYMS gene expression at 24 h, whereas the sequential combination reduced SLC19A1 gene expression. In vivo experiments confirmed the enhanced antitumor activity of the 5-FU + NaLV simultaneous combination with a good toxicity profile, whereas the sequential combination with CaLV failed to potentiate 5-FU activity. In conclusion, only the simultaneous, but not the consecutive, in vitro and in vivo combination of 5-FU and both folinate salt formulations potentiated the antiproliferative effects of the drugs.

Team Teaching in Social Work: Sharing Power with Bachelor of Social Work Students

ERIC Educational Resources Information Center

Zapf, Michael Kim; Jerome, Les; Williams, Margaret

2011-01-01

Team teaching in social work education usually involves sequential lectures delivered by different instructors--relay or tag-team teaching. Truly collaborative or collegial team teaching involves a committed group of diverse instructors interacting together as equals in the classroom. Having more than one teacher in the classroom confounds…

Changes in brain activation during working memory and facial recognition tasks in patients with bipolar disorder with Lamotrigine monotherapy.

PubMed

Haldane, Morgan; Jogia, Jigar; Cobb, Annabel; Kozuch, Eliza; Kumari, Veena; Frangou, Sophia

2008-01-01

Verbal working memory and emotional self-regulation are impaired in Bipolar Disorder (BD). Our aim was to investigate the effect of Lamotrigine (LTG), which is effective in the clinical management of BD, on the neural circuits subserving working memory and emotional processing. Functional Magnetic Resonance Imaging data from 12 stable BD patients was used to detect LTG-induced changes as the differences in brain activity between drug-free and post-LTG monotherapy conditions during a verbal working memory (N-back sequential letter task) and an angry facial affect recognition task. For both tasks, LGT monotherapy compared to baseline was associated with increased activation mostly within the prefrontal cortex and cingulate gyrus, in regions normally engaged in verbal working memory and emotional processing. Therefore, LTG monotherapy in BD patients may enhance cortical function within neural circuits involved in memory and emotional self-regulation.

The Adam language: Ada extended with support for multiway activities

NASA Technical Reports Server (NTRS)

Charlesworth, Arthur

1993-01-01

The Adam language is an extension of Ada that supports multiway activities, which are cooperative activities involving two or more processes. This support is provided by three new constructs: diva procedures, meet statements, and multiway accept statements. Diva procedures are recursive generic procedures having a particular restrictive syntax that facilitates translation for parallel computers. Meet statements and multiway accept statements provide two ways to express a multiway rendezvous, which is an n-way rendezvous generalizing Ada's 2-way rendezvous. While meet statements tend to have simpler rules than multiway accept statements, the latter approach is a more straightforward extension of Ada. The only nonnull statements permitted within meet statements and multiway accept statements are calls on instantiated diva procedures. A call on an instantiated diva procedure is also permitted outside a multiway rendezvous; thus sequential Adam programs using diva procedures can be written. Adam programs are translated into Ada programs appropriate for use on parallel computers.

ATP hydrolysis in Eg5 kinesin involves a catalytic two-water mechanism.

PubMed

Parke, Courtney L; Wojcik, Edward J; Kim, Sunyoung; Worthylake, David K

2010-02-19

Motor proteins couple steps in ATP binding and hydrolysis to conformational switching both in and remote from the active site. In our kinesin.AMPPPNP crystal structure, closure of the active site results in structural transformations appropriate for microtubule binding and organizes an orthosteric two-water cluster. We conclude that a proton is shared between the lytic water, positioned for gamma-phosphate attack, and a second water that serves as a general base. To our knowledge, this is the first experimental detection of the catalytic base for any ATPase. Deprotonation of the second water by switch residues likely triggers subsequent large scale structural rearrangements. Therefore, the catalytic base is responsible for initiating nucleophilic attack of ATP and for relaying the positive charge over long distances to initiate mechanotransduction. Coordination of switch movements via sequential proton transfer along paired water clusters may be universal for nucleotide triphosphatases with conserved active sites, such as myosins and G-proteins.

The impact of comorbid body dysmorphic disorder on the response to sequential pharmacological trials for obsessive-compulsive disorder.

PubMed

Diniz, Juliana B; Costa, Daniel Lc; Cassab, Raony Cc; Pereira, Carlos Ab; Miguel, Euripedes C; Shavitt, Roseli G

2014-06-01

Our aim was to investigate the impact of comorbid body dysmorphic disorder (BDD) on the response to sequential pharmacological trials in adult obsessive-compulsive disorder (OCD) patients. The sequential trial initially involved fluoxetine monotherapy followed by one of three randomized, add-on strategies: placebo, clomipramine or quetiapine. We included 138 patients in the initial phase of fluoxetine, up to 80 mg or the maximum tolerated dosage, for 12 weeks. We invited 70 non-responders to participate in the add-on trial; as 54 accepted, we allocated 18 to each treatment group and followed them for an additional 12 weeks. To evaluate the combined effects of sex, age, age at onset, initial severity, type of augmentation and BDD on the response to sequential treatments, we constructed a model using generalized estimating equations (GEE). Of the 39 patients who completed the study (OCD-BDD, n = 13; OCD-non-BDD, n = 26), the OCD-BDD patients were less likely to be classified as responders than the OCD-non-BDD patients (Pearson Chi-Square = 4.4; p = 0.036). In the GEE model, BDD was not significantly associated with a worse response to sequential treatments (z-robust = 1.77; p = 0.07). The predictive potential of BDD regarding sequential treatment strategies for OCD did not survive when the analyses were controlled for other clinical characteristics. © The Author(s) 2013.

Phenolic content and antioxidant activity of Hibiscus cannabinus L. seed extracts after sequential solvent extraction.

PubMed

Yusri, Noordin Mohd; Chan, Kim Wei; Iqbal, Shahid; Ismail, Maznah

2012-10-25

A sequential solvent extraction scheme was employed for the extraction of antioxidant compounds from kenaf (Hibiscus cannabinus L.) seeds. Yield of extracts varied widely among the solvents and was the highest for hexane extract (16.6% based on dry weight basis), while water extract exhibited the highest total phenolic content (18.78 mg GAE/g extract), total flavonoid content (2.49 mg RE/g extract), and antioxidant activities (p < 0.05). DPPH and hydroxyl radical scavenging, β-carotene bleaching, metal chelating activity, ferric thiocyanate and thiobarbituric acid reactive substances assays were employed to comprehensively assess the antioxidant potential of different solvent extracts prepared sequentially. Besides water, methanolic extract also exhibited high retardation towards the formation of hydroperoxides and thiobarbituric acid reactive substances in the total antioxidant activity tests (p < 0.05). As conclusion, water and methanol extracts of kenaf seed may potentially serve as new sources of antioxidants for food and nutraceutical applications.

Optimization, formulation, and characterization of multiflavonoids-loaded flavanosome by bulk or sequential technique

PubMed Central

Karthivashan, Govindarajan; Masarudin, Mas Jaffri; Kura, Aminu Umar; Abas, Faridah; Fakurazi, Sharida

2016-01-01

This study involves adaptation of bulk or sequential technique to load multiple flavonoids in a single phytosome, which can be termed as “flavonosome”. Three widely established and therapeutically valuable flavonoids, such as quercetin (Q), kaempferol (K), and apigenin (A), were quantified in the ethyl acetate fraction of Moringa oleifera leaves extract and were commercially obtained and incorporated in a single flavonosome (QKA–phosphatidylcholine) through four different methods of synthesis – bulk (M1) and serialized (M2) co-sonication and bulk (M3) and sequential (M4) co-loading. The study also established an optimal formulation method based on screening the synthesized flavonosomes with respect to their size, charge, polydispersity index, morphology, drug–carrier interaction, antioxidant potential through in vitro 1,1-diphenyl-2-picrylhydrazyl kinetics, and cytotoxicity evaluation against human hepatoma cell line (HepaRG). Furthermore, entrapment and loading efficiency of flavonoids in the optimal flavonosome have been identified. Among the four synthesis methods, sequential loading technique has been optimized as the best method for the synthesis of QKA–phosphatidylcholine flavonosome, which revealed an average diameter of 375.93±33.61 nm, with a zeta potential of −39.07±3.55 mV, and the entrapment efficiency was >98% for all the flavonoids, whereas the drug-loading capacity of Q, K, and A was 31.63%±0.17%, 34.51%±2.07%, and 31.79%±0.01%, respectively. The in vitro 1,1-diphenyl-2-picrylhydrazyl kinetics of the flavonoids indirectly depicts the release kinetic behavior of the flavonoids from the carrier. The QKA-loaded flavonosome had no indication of toxicity toward human hepatoma cell line as shown by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide result, wherein even at the higher concentration of 200 µg/mL, the flavonosomes exert >85% of cell viability. These results suggest that sequential loading technique may be a promising nanodrug delivery system for loading multiflavonoids in a single entity with sustained activity as an antioxidant, hepatoprotective, and hepatosupplement candidate. PMID:27555765

Optimization, formulation, and characterization of multiflavonoids-loaded flavanosome by bulk or sequential technique.

PubMed

Karthivashan, Govindarajan; Masarudin, Mas Jaffri; Kura, Aminu Umar; Abas, Faridah; Fakurazi, Sharida

2016-01-01

This study involves adaptation of bulk or sequential technique to load multiple flavonoids in a single phytosome, which can be termed as "flavonosome". Three widely established and therapeutically valuable flavonoids, such as quercetin (Q), kaempferol (K), and apigenin (A), were quantified in the ethyl acetate fraction of Moringa oleifera leaves extract and were commercially obtained and incorporated in a single flavonosome (QKA-phosphatidylcholine) through four different methods of synthesis - bulk (M1) and serialized (M2) co-sonication and bulk (M3) and sequential (M4) co-loading. The study also established an optimal formulation method based on screening the synthesized flavonosomes with respect to their size, charge, polydispersity index, morphology, drug-carrier interaction, antioxidant potential through in vitro 1,1-diphenyl-2-picrylhydrazyl kinetics, and cytotoxicity evaluation against human hepatoma cell line (HepaRG). Furthermore, entrapment and loading efficiency of flavonoids in the optimal flavonosome have been identified. Among the four synthesis methods, sequential loading technique has been optimized as the best method for the synthesis of QKA-phosphatidylcholine flavonosome, which revealed an average diameter of 375.93±33.61 nm, with a zeta potential of -39.07±3.55 mV, and the entrapment efficiency was >98% for all the flavonoids, whereas the drug-loading capacity of Q, K, and A was 31.63%±0.17%, 34.51%±2.07%, and 31.79%±0.01%, respectively. The in vitro 1,1-diphenyl-2-picrylhydrazyl kinetics of the flavonoids indirectly depicts the release kinetic behavior of the flavonoids from the carrier. The QKA-loaded flavonosome had no indication of toxicity toward human hepatoma cell line as shown by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide result, wherein even at the higher concentration of 200 µg/mL, the flavonosomes exert >85% of cell viability. These results suggest that sequential loading technique may be a promising nanodrug delivery system for loading multiflavonoids in a single entity with sustained activity as an antioxidant, hepatoprotective, and hepatosupplement candidate.

In situ formation deposited ZnO nanoparticles on silk fabrics under ultrasound irradiation.

PubMed

Khanjani, Somayeh; Morsali, Ali; Joo, Sang W

2013-03-01

Deposition of zinc(II) oxide (ZnO) nanoparticles on the surface of silk fabrics was prepared by sequential dipping steps in alternating bath of potassium hydroxide and zinc nitrate under ultrasound irradiation. This coating involves in situ generation and deposition of ZnO in a one step. The effects of ultrasound irradiation, concentration and sequential dipping steps on growth of the ZnO nanoparticles have been studied. Results show a decrease in the particles size as increasing power of ultrasound irradiation. Also, increasing of the concentration and sequential dipping steps increase particle size. The physicochemical properties of the nanoparticles were determined by powder X-ray diffraction (XRD), scanning electron microscopy (SEM) and wavelength dispersive X-ray (WDX). Copyright © 2012 Elsevier B.V. All rights reserved.

Totally endoscopic sequential arterial coronary artery bypass grafting on the beating heart

PubMed Central

Ak, Koray; Wimmer-Greinecker, Gerhard; Dzemali, Omer; Moritz, Anton; Dogan, Selami

2007-01-01

A 50-year-old man was referred to the Department of Thoracic and Cardiovascular Surgery at the Johann Wolfgang-Goethe University (Frankfurt, Germany) with angina on exertion. An evaluation revealed critical stenosis involving the proximal portion of the left anterior descending artery and the first diagonal branch. The patient underwent successful sequential grafting of the left internal mammary artery to the left anterior descending artery and the diagonal branch using a totally endoscopic coronary artery bypass grafting technique on the beating heart with a new version of the da Vinci Surgical System (Intuitive Surgical, USA). To the authors’ knowledge, this is the first report in literature to describe sequential arterial off-pump grafting of two anterior wall target vessels using a totally endoscopic technique on the beating heart. PMID:17440646

Effects of neostriatal 6-OHDA lesion on performance in a rat sequential reaction time task.

PubMed

Domenger, D; Schwarting, R K W

2008-10-31

Work in humans and monkeys has provided evidence that the basal ganglia, and the neurotransmitter dopamine therein, play an important role for sequential learning and performance. Compared to primates, experimental work in rodents is rather sparse, largely due to the fact that tasks comparable to the human ones, especially serial reaction time tasks (SRTT), had been lacking until recently. We have developed a rat model of the SRTT, which allows to study neural correlates of sequential performance and motor sequence execution. Here, we report the effects of dopaminergic neostriatal lesions, performed using bilateral 6-hydroxydopamine injections, on performance of well-trained rats tested in our SRTT. Sequential behavior was measured in two ways: for one, the effects of small violations of otherwise well trained sequences were examined as a measure of attention and automation. Secondly, sequential versus random performance was compared as a measure of sequential learning. Neurochemically, the lesions led to sub-total dopamine depletions in the neostriatum, which ranged around 60% in the lateral, and around 40% in the medial neostriatum. These lesions led to a general instrumental impairment in terms of reduced speed (response latencies) and response rate, and these deficits were correlated with the degree of striatal dopamine loss. Furthermore, the violation test indicated that the lesion group conducted less automated responses. The comparison of random versus sequential responding showed that the lesion group did not retain its superior sequential performance in terms of speed, whereas they did in terms of accuracy. Also, rats with lesions did not improve further in overall performance as compared to pre-lesion values, whereas controls did. These results support previous results that neostriatal dopamine is involved in instrumental behaviour in general. Also, these lesions are not sufficient to completely abolish sequential performance, at least when acquired before lesion as tested here.

Exosites in the substrate specificity of blood coagulation reactions.

PubMed

Bock, P E; Panizzi, P; Verhamme, I M A

2007-07-01

The specificity of blood coagulation proteinases for substrate, inhibitor, and effector recognition is mediated by exosites on the surfaces of the catalytic domains, physically separated from the catalytic site. Some thrombin ligands bind specifically to either exosite I or II, while others engage both exosites. The involvement of different, overlapping constellations of exosite residues enables binding of structurally diverse ligands. The flexibility of the thrombin structure is central to the mechanism of complex formation and the specificity of exosite interactions. Encounter complex formation is driven by electrostatic ligand-exosite interactions, followed by conformational rearrangement to a stable complex. Exosites on some zymogens are in low affinity proexosite states and are expressed concomitant with catalytic site activation. The requirement for exosite expression controls the specificity of assembly of catalytic complexes on the coagulation pathway, such as the membrane-bound factor Xa*factor Va (prothrombinase) complex, and prevents premature assembly. Substrate recognition by prothrombinase involves a two-step mechanism with initial docking of prothrombin to exosites, followed by a conformational change to engage the FXa catalytic site. Prothrombin and its activation intermediates bind prothrombinase in two alternative conformations determined by the zymogen to proteinase transition that are hypothesized to involve prothrombin (pro)exosite I interactions with FVa, which underpin the sequential activation pathway. The role of exosites as the major source of substrate specificity has stimulated development of exosite-targeted anticoagulants for treatment of thrombosis.

Firing rate dynamics in the hippocampus induced by trajectory learning.

PubMed

Ji, Daoyun; Wilson, Matthew A

2008-04-30

The hippocampus is essential for spatial navigation, which may involve sequential learning. However, how the hippocampus encodes new sequences in familiar environments is unknown. To study the impact of novel spatial sequences on the activity of hippocampal neurons, we monitored hippocampal ensembles while rats learned to switch from two familiar trajectories to a new one in a familiar environment. Here, we show that this novel spatial experience induces two types of changes in firing rates, but not locations of hippocampal place cells. First, place-cell firing rates on the two familiar trajectories start to change before the actual behavioral switch to the new trajectory. Second, repeated exposure on the new trajectory is associated with an increased dependence of place-cell firing rates on immediate past locations. The result suggests that sequence encoding in the hippocampus may involve integration of information about the recent past into current state.

Firing Rate Dynamics in the Hippocampus Induced by Trajectory Learning

PubMed Central

Wilson, Matthew A.

2008-01-01

The hippocampus is essential for spatial navigation, which may involve sequential learning. However, how the hippocampus encodes new sequences in familiar environments is unknown. To study the impact of novel spatial sequences on the activity of hippocampal neurons, we monitored hippocampal ensembles while rats learned to switch from two familiar trajectories to a new one in a familiar environment. Here, we show that this novel spatial experience induces two types of changes in firing rates, but not locations of hippocampal place cells. First, place-cell firing rates on the two familiar trajectories start to change before the actual behavioral switch to the new trajectory. Second, repeated exposure on the new trajectory is associated with an increased dependence of place-cell firing rates on immediate past locations. The result suggests that sequence encoding in the hippocampus may involve integration of information about the recent past into current state. PMID:18448645

Dynamic anticipatory processing of hierarchical sequential events: a common role for Broca's area and ventral premotor cortex across domains?

PubMed

Fiebach, Christian J; Schubotz, Ricarda I

2006-05-01

This paper proposes a domain-general model for the functional contribution of ventral premotor cortex (PMv) and adjacent Broca's area to perceptual, cognitive, and motor processing. We propose to understand this frontal region as a highly flexible sequence processor, with the PMv mapping sequential events onto stored structural templates and Broca's Area involved in more complex, hierarchical or hypersequential processing. This proposal is supported by reference to previous functional neuroimaging studies investigating abstract sequence processing and syntactic processing.

Wald Sequential Probability Ratio Test for Analysis of Orbital Conjunction Data

NASA Technical Reports Server (NTRS)

Carpenter, J. Russell; Markley, F. Landis; Gold, Dara

2013-01-01

We propose a Wald Sequential Probability Ratio Test for analysis of commonly available predictions associated with spacecraft conjunctions. Such predictions generally consist of a relative state and relative state error covariance at the time of closest approach, under the assumption that prediction errors are Gaussian. We show that under these circumstances, the likelihood ratio of the Wald test reduces to an especially simple form, involving the current best estimate of collision probability, and a similar estimate of collision probability that is based on prior assumptions about the likelihood of collision.

Treating convection in sequential solvers

NASA Technical Reports Server (NTRS)

Shyy, Wei; Thakur, Siddharth

1992-01-01

The treatment of the convection terms in the sequential solver, a standard procedure found in virtually all pressure based algorithms, to compute the flow problems with sharp gradients and source terms is investigated. Both scalar model problems and one-dimensional gas dynamics equations have been used to study the various issues involved. Different approaches including the use of nonlinear filtering techniques and adoption of TVD type schemes have been investigated. Special treatments of the source terms such as pressure gradients and heat release have also been devised, yielding insight and improved accuracy of the numerical procedure adopted.

Sterol glycosyltransferases--the enzymes that modify sterols.

PubMed

Chaturvedi, Pankaj; Misra, Pratibha; Tuli, Rakesh

2011-09-01

Sterols are important components of cell membranes, hormones, signalling molecules and defense-related biotic and abiotic chemicals. Sterol glycosyltransferases (SGTs) are enzymes involved in sterol modifications and play an important role in metabolic plasticity during adaptive responses. The enzymes are classified as a subset of family 1 glycosyltransferases due to the presence of a signature motif in their primary sequence. These enzymes follow a compulsory order sequential mechanism forming a ternary complex. The diverse applications of sterol glycosides, like cytotoxic and apoptotic activity, anticancer activity, medicinal values, anti-stress roles and anti-insect and antibacterial properties, draws attention towards their synthesis mechanisms. Many secondary metabolites are derived from sterol pathways, which are important in defense mechanisms against pathogens. SGTs in plants are involved in changed sensitivity to stress hormones and their agrochemical analogs and changed tolerance to biotic and abiotic stresses. SGTs that glycosylate steroidal hormones, such as brassinosteroids, function as growth and development regulators in plants. In terms of metabolic roles, it can be said that SGTs occupy important position in plant metabolism and may offer future tools for crop improvement.

Functionalized sorbent for chemical separations and sequential forming process

DOEpatents

Fryxell, Glen E [Kennewick, WA; Zemanian, Thomas S [Richland, WA

2012-03-20

A highly functionalized sorbent and sequential process for making are disclosed. The sorbent includes organic short-length amino silanes and organic oligomeric polyfunctional amino silanes that are dispersed within pores of a porous support that form a 3-dimensional structure containing highly functionalized active binding sites for sorption of analytes.

The Nature of Phonological Encoding During Spoken Word Retrieval.

ERIC Educational Resources Information Center

Sullivan, Michael P.; Riffel, Brian

1999-01-01

Examined whether phonological selection occurs sequentially or in parallel. College students named picture primes and targets, with varied response stimulus intervals between primes and targets. Results were consistent with Dell's (1988) two-stage sequential model of encoding, which shows an initial parallel activation within a lexical network…

Parental Beliefs and Experiences Regarding Involvement in Intervention for Their Child with Speech Sound Disorder

ERIC Educational Resources Information Center

Watts Pappas, Nicole; McAllister, Lindy; McLeod, Sharynne

2016-01-01

Parental beliefs and experiences regarding involvement in speech intervention for their child with mild to moderate speech sound disorder (SSD) were explored using multiple, sequential interviews conducted during a course of treatment. Twenty-one interviews were conducted with seven parents of six children with SSD: (1) after their child's initial…

Optimal decision making on the basis of evidence represented in spike trains.

PubMed

Zhang, Jiaxiang; Bogacz, Rafal

2010-05-01

Experimental data indicate that perceptual decision making involves integration of sensory evidence in certain cortical areas. Theoretical studies have proposed that the computation in neural decision circuits approximates statistically optimal decision procedures (e.g., sequential probability ratio test) that maximize the reward rate in sequential choice tasks. However, these previous studies assumed that the sensory evidence was represented by continuous values from gaussian distributions with the same variance across alternatives. In this article, we make a more realistic assumption that sensory evidence is represented in spike trains described by the Poisson processes, which naturally satisfy the mean-variance relationship observed in sensory neurons. We show that for such a representation, the neural circuits involving cortical integrators and basal ganglia can approximate the optimal decision procedures for two and multiple alternative choice tasks.

Cocaine induces astrocytosis through ER stress-mediated activation of autophagy

PubMed Central

Periyasamy, Palsamy; Guo, Ming-Lei; Buch, Shilpa

2016-01-01

ABSTRACT Cocaine is known to induce inflammation, thereby contributing in part, to the pathogenesis of neurodegeneration. A recent study from our lab has revealed a link between macroautophagy/autophagy and microglial activation. The current study was aimed at investigating whether cocaine could also mediate activation of astrocytes and, whether this process involved induction of autophagy. Our findings demonstrated that cocaine mediated the activation of astrocytes by altering the levels of autophagy markers, such as BECN1, ATG5, MAP1LC3B-II, and SQSTM1 in both human A172 astrocytoma cells and primary human astrocytes. Furthermore, cocaine treatment resulted in increased formation of endogenous MAP1LC3B puncta in human astrocytes. Additionally, astrocytes transfected with the GFP-MAP1LC3B plasmid also demonstrated cocaine-mediated upregulation of the green fluorescent MAP1LC3B puncta. Cocaine-mediated induction of autophagy involved upstream activation of ER stress proteins such as EIF2AK3, ERN1, ATF6 since blockage of autophagy using either pharmacological or gene-silencing approaches, had no effect on cocaine-mediated induction of ER stress. Using both pharmacological and gene-silencing approaches to block either ER stress or autophagy, our findings demonstrated that cocaine-induced activation of astrocytes (measured by increased levels of GFAP) involved sequential activation of ER stress and autophagy. Cocaine-mediated-increased upregulation of GFAP correlated with increased expression of proinflammatory mediators such as TNF, IL1B, and IL6. In conclusion, these findings reveal an association between ER stress-mediated autophagy and astrogliosis in cocaine-treated astrocytes. Intervention of ER stress and/or autophagy signaling would thus be promising therapeutic targets for abrogating cocaine-mediated neuroinflammation. PMID:27337297

Cocaine induces astrocytosis through ER stress-mediated activation of autophagy.

PubMed

Periyasamy, Palsamy; Guo, Ming-Lei; Buch, Shilpa

2016-08-02

Cocaine is known to induce inflammation, thereby contributing in part, to the pathogenesis of neurodegeneration. A recent study from our lab has revealed a link between macroautophagy/autophagy and microglial activation. The current study was aimed at investigating whether cocaine could also mediate activation of astrocytes and, whether this process involved induction of autophagy. Our findings demonstrated that cocaine mediated the activation of astrocytes by altering the levels of autophagy markers, such as BECN1, ATG5, MAP1LC3B-II, and SQSTM1 in both human A172 astrocytoma cells and primary human astrocytes. Furthermore, cocaine treatment resulted in increased formation of endogenous MAP1LC3B puncta in human astrocytes. Additionally, astrocytes transfected with the GFP-MAP1LC3B plasmid also demonstrated cocaine-mediated upregulation of the green fluorescent MAP1LC3B puncta. Cocaine-mediated induction of autophagy involved upstream activation of ER stress proteins such as EIF2AK3, ERN1, ATF6 since blockage of autophagy using either pharmacological or gene-silencing approaches, had no effect on cocaine-mediated induction of ER stress. Using both pharmacological and gene-silencing approaches to block either ER stress or autophagy, our findings demonstrated that cocaine-induced activation of astrocytes (measured by increased levels of GFAP) involved sequential activation of ER stress and autophagy. Cocaine-mediated-increased upregulation of GFAP correlated with increased expression of proinflammatory mediators such as TNF, IL1B, and IL6. In conclusion, these findings reveal an association between ER stress-mediated autophagy and astrogliosis in cocaine-treated astrocytes. Intervention of ER stress and/or autophagy signaling would thus be promising therapeutic targets for abrogating cocaine-mediated neuroinflammation.

Spatial-sequential and spatial-simultaneous working memory in individuals with Williams syndrome.

PubMed

Lanfranchi, Silvia; De Mori, Letizia; Mammarella, Irene C; Carretti, Barbara; Vianello, Renzo

2015-05-01

The aim of the present study was to compare visuospatial working memory performance in 18 individuals with Williams syndrome (WS) and 18 typically developing (TD) children matched for nonverbal mental age. Two aspects were considered: task presentation format (i.e., spatial-sequential or spatial-simultaneous), and level of attentional control (i.e., passive or active tasks). Our results showed that individuals with WS performed less well than TD children in passive spatial-simultaneous tasks, but not in passive spatial-sequential tasks. The former's performance was also worse in both active tasks. These findings suggest an impairment in the spatial-simultaneous working memory of individuals with WS, together with a more generalized difficulty in tasks requiring information storage and concurrent processing, as seen in other etiologies of intellectual disability.

Unexpected regioselective carbon-hydrogen bond activation/cyclization of indolyl aldehydes or ketones with alkynes to benzo-fused oxindoles.

PubMed

Liu, Xingyan; Li, Gaocan; Song, Feijie; You, Jingsong

2014-09-25

Rhodium-catalyzed carbon-hydrogen bond activation has attracted great interest in the construction of carbon-carbon and carbon-heteroatom bonds. In recent years, transition metal-mediated oxygen transposition through a 'dehydration-rehydration' process has been considered as a promising strategy towards oxygen-functionalized compounds. Here we describe an unexpected rhodium-catalyzed regioselective carbon-hydrogen bond activation/cyclization of easily available indolyl aldehydes or ketones with alkynes to afford benzo-fused oxindoles, involving the sequential carbonyl-assisted carbon-hydrogen activation of the indole ring at the 4-position, [4+2] cyclization, aromatization via dehydration, nucleophilic addition of water to iminium and oxidation. Isotopic labelling experiments disclose the occurrence of apparent oxygen transposition via dehydration-rehydration from the indolyl-3-carbonyl group to the 2-position of pyrrole to forge a new carbonyl bond. The tandem reaction has been used as the key step for the concise synthesis of priolines, a type of alkaloid isolated from the roots of Salvia prionitis.

Comparative efficacy of simultaneous versus sequential multiple health behavior change interventions among adults: A systematic review of randomised trials.

PubMed

James, Erica; Freund, Megan; Booth, Angela; Duncan, Mitch J; Johnson, Natalie; Short, Camille E; Wolfenden, Luke; Stacey, Fiona G; Kay-Lambkin, Frances; Vandelanotte, Corneel

2016-08-01

Growing evidence points to the benefits of addressing multiple health behaviors rather than single behaviors. This review evaluates the relative effectiveness of simultaneous and sequentially delivered multiple health behavior change (MHBC) interventions. Secondary aims were to identify: a) the most effective spacing of sequentially delivered components; b) differences in efficacy of MHBC interventions for adoption/cessation behaviors and lifestyle/addictive behaviors, and; c) differences in trial retention between simultaneously and sequentially delivered interventions. MHBC intervention trials published up to October 2015 were identified through a systematic search. Eligible trials were randomised controlled trials that directly compared simultaneous and sequential delivery of a MHBC intervention. A narrative synthesis was undertaken. Six trials met the inclusion criteria and across these trials the behaviors targeted were smoking, diet, physical activity, and alcohol consumption. Three trials reported a difference in intervention effect between a sequential and simultaneous approach in at least one behavioral outcome. Of these, two trials favoured a sequential approach on smoking. One trial favoured a simultaneous approach on fat intake. There was no difference in retention between sequential and simultaneous approaches. There is limited evidence regarding the relative effectiveness of sequential and simultaneous approaches. Given only three of the six trials observed a difference in intervention effectiveness for one health behavior outcome, and the relatively consistent finding that the sequential and simultaneous approaches were more effective than a usual/minimal care control condition, it appears that both approaches should be considered equally efficacious. PROSPERO registration number: CRD42015027876. Copyright © 2016 Elsevier Inc. All rights reserved.

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.

Security Games Involving Search and Patrolling

DTIC Science & Technology

2017-04-28

AFRL-AFOSR-UK-TR-2017-0032 Security Games Involving Search and Patrolling Steve Alpern UNIVERSITY OF WARWICK Final Report 04/28/2017 DISTRIBUTION A...From - To) 01 Feb 2014 to 31 Jan 2017 4. TITLE AND SUBTITLE Security Games Involving Search and Patrolling 5a.  CONTRACT NUMBER 5b.  GRANT NUMBER...interview sequentially has been recently published. Work of Alpern and Howard (2016) solves a class of winner-take-all games which include the

How hierarchical is language use?

PubMed Central

Frank, Stefan L.; Bod, Rens; Christiansen, Morten H.

2012-01-01

It is generally assumed that hierarchical phrase structure plays a central role in human language. However, considerations of simplicity and evolutionary continuity suggest that hierarchical structure should not be invoked too hastily. Indeed, recent neurophysiological, behavioural and computational studies show that sequential sentence structure has considerable explanatory power and that hierarchical processing is often not involved. In this paper, we review evidence from the recent literature supporting the hypothesis that sequential structure may be fundamental to the comprehension, production and acquisition of human language. Moreover, we provide a preliminary sketch outlining a non-hierarchical model of language use and discuss its implications and testable predictions. If linguistic phenomena can be explained by sequential rather than hierarchical structure, this will have considerable impact in a wide range of fields, such as linguistics, ethology, cognitive neuroscience, psychology and computer science. PMID:22977157

The Domino Way to Heterocycles

PubMed Central

Padwa, Albert; Bur, Scott K.

2007-01-01

Sequential transformations enable the facile synthesis of complex target molecules from simple building blocks in a single preparative step. Their value is amplified if they also create multiple stereogenic centers. In the ongoing search for new domino processes, emphasis is usually placed on sequential reactions which occur cleanly and without forming by-products. As a prerequisite for an ideally proceeding one-pot sequential transformation, the reactivity pattern of all participating components has to be such that each building block gets involved in a reaction only when it is supposed to do so. The development of sequences that combine transformations of fundamentally different mechanisms broadens the scope of such procedures in synthetic chemistry. This mini review contains a representative sampling from the last 15 years on the kinds of reactions that have been sequenced into cascades to produce heterocyclic molecules. PMID:17940591

The Evolution of Gene Regulatory Networks that Define Arthropod Body Plans.

PubMed

Auman, Tzach; Chipman, Ariel D

2017-09-01

Our understanding of the genetics of arthropod body plan development originally stems from work on Drosophila melanogaster from the late 1970s and onward. In Drosophila, there is a relatively detailed model for the network of gene interactions that proceeds in a sequential-hierarchical fashion to define the main features of the body plan. Over the years, we have a growing understanding of the networks involved in defining the body plan in an increasing number of arthropod species. It is now becoming possible to tease out the conserved aspects of these networks and to try to reconstruct their evolution. In this contribution, we focus on several key nodes of these networks, starting from early patterning in which the main axes are determined and the broad morphological domains of the embryo are defined, and on to later stage wherein the growth zone network is active in sequential addition of posterior segments. The pattern of conservation of networks is very patchy, with some key aspects being highly conserved in all arthropods and others being very labile. Many aspects of early axis patterning are highly conserved, as are some aspects of sequential segment generation. In contrast, regional patterning varies among different taxa, and some networks, such as the terminal patterning network, are only found in a limited range of taxa. The growth zone segmentation network is ancient and is probably plesiomorphic to all arthropods. In some insects, it has undergone significant modification to give rise to a more hardwired network that generates individual segments separately. In other insects and in most arthropods, the sequential segmentation network has undergone a significant amount of systems drift, wherein many of the genes have changed. However, it maintains a conserved underlying logic and function. © The Author 2017. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email: journals.permissions@oup.com.

Peroxygenase-Catalyzed Fatty Acid Epoxidation in Cereal Seeds (Sequential Oxidation of Linoleic Acid into 9(S),12(S),13(S)-Trihydroxy-10(E)-Octadecenoic Acid).

PubMed Central

Hamberg, M.; Hamberg, G.

1996-01-01

Peroxygenase-catalyzed epoxidation of oleic acid in preparations of cereal seeds was investigated. The 105,000g particle fraction of oat (Avena sativa) seed homogenate showed high peroxygenase activity, i.e. 3034 [plus or minus] 288 and 2441 [plus or minus] 168 nmol (10 min)-1 mg-1 protein in two cultivars, whereas the corresponding fraction obtained from barley (Hordeum vulgare and Hordeum distichum), rye (Secale cereale), and wheat (Triticum aestivum) showed only weak activity, i.e. 13 to 138 nmol (10 min)-1 mg-1 protein. In subcellular fractions of oat seed homogenate, peroxygenase specific activity was highest in the 105,000g particle fraction, whereas lipoxygenase activity was more evenly distributed and highest in the 105,000g supernatant fraction. Incubation of [1-14C]linoleic acid with the 105,000g supernatant of oat seed homogenate led to the formation of several metabolites, i.e. in order of decreasing abundance, 9(S)-hydroxy-10(E),12(Z)-octadecadienoic acid, 9(S),12(S),13(S)-trihydroxy-10(E)-octadecenoic acid, cis-9,10-epoxy-12(Z)-octadecenoic acid [mainly the 9(R),10(S) enantiomer], cis-12,13-epoxy-9(Z)-octadecenoic acid [mainly the 12(R),13(S) enantiomer], threo-12,13-dihydroxy-9(Z)-octadecenoic acid, and 12(R),13(S)-epoxy-9(S)-hydroxy-10(E)-octadecenoic acid. Incubation of linoleic acid with the 105,000g particle fraction gave a similar, but not identical, pattern of metabolites. Conversion of linoleic acid into 9(S),12(S),13(S)-trihydroxy-10(E)-octadecenoic acid, a naturally occurring oxylipin with antifungal properties, took place by a pathway involving sequential catalysis by lipoxygenase, peroxygenase, and epoxide hydrolase. PMID:12226220

Group-sequential three-arm noninferiority clinical trial designs

PubMed Central

Ochiai, Toshimitsu; Hamasaki, Toshimitsu; Evans, Scott R.; Asakura, Koko; Ohno, Yuko

2016-01-01

We discuss group-sequential three-arm noninferiority clinical trial designs that include active and placebo controls for evaluating both assay sensitivity and noninferiority. We extend two existing approaches, the fixed margin and fraction approaches, into a group-sequential setting with two decision-making frameworks. We investigate the operating characteristics including power, Type I error rate, maximum and expected sample sizes, as design factors vary. In addition, we discuss sample size recalculation and its’ impact on the power and Type I error rate via a simulation study. PMID:26892481

Sequential sampling of visual objects during sustained attention.

PubMed

Jia, Jianrong; Liu, Ling; Fang, Fang; Luo, Huan

2017-06-01

In a crowded visual scene, attention must be distributed efficiently and flexibly over time and space to accommodate different contexts. It is well established that selective attention enhances the corresponding neural responses, presumably implying that attention would persistently dwell on the task-relevant item. Meanwhile, recent studies, mostly in divided attentional contexts, suggest that attention does not remain stationary but samples objects alternately over time, suggesting a rhythmic view of attention. However, it remains unknown whether the dynamic mechanism essentially mediates attentional processes at a general level. Importantly, there is also a complete lack of direct neural evidence reflecting whether and how the brain rhythmically samples multiple visual objects during stimulus processing. To address these issues, in this study, we employed electroencephalography (EEG) and a temporal response function (TRF) approach, which can dissociate responses that exclusively represent a single object from the overall neuronal activity, to examine the spatiotemporal characteristics of attention in various attentional contexts. First, attention, which is characterized by inhibitory alpha-band (approximately 10 Hz) activity in TRFs, switches between attended and unattended objects every approximately 200 ms, suggesting a sequential sampling even when attention is required to mostly stay on the attended object. Second, the attentional spatiotemporal pattern is modulated by the task context, such that alpha-mediated switching becomes increasingly prominent as the task requires a more uniform distribution of attention. Finally, the switching pattern correlates with attentional behavioral performance. Our work provides direct neural evidence supporting a generally central role of temporal organization mechanism in attention, such that multiple objects are sequentially sorted according to their priority in attentional contexts. The results suggest that selective attention, in addition to the classically posited attentional "focus," involves a dynamic mechanism for monitoring all objects outside of the focus. Our findings also suggest that attention implements a space (object)-to-time transformation by acting as a series of concatenating attentional chunks that operate on 1 object at a time.

Sequential sampling of visual objects during sustained attention

PubMed Central

Jia, Jianrong; Liu, Ling; Fang, Fang

2017-01-01

In a crowded visual scene, attention must be distributed efficiently and flexibly over time and space to accommodate different contexts. It is well established that selective attention enhances the corresponding neural responses, presumably implying that attention would persistently dwell on the task-relevant item. Meanwhile, recent studies, mostly in divided attentional contexts, suggest that attention does not remain stationary but samples objects alternately over time, suggesting a rhythmic view of attention. However, it remains unknown whether the dynamic mechanism essentially mediates attentional processes at a general level. Importantly, there is also a complete lack of direct neural evidence reflecting whether and how the brain rhythmically samples multiple visual objects during stimulus processing. To address these issues, in this study, we employed electroencephalography (EEG) and a temporal response function (TRF) approach, which can dissociate responses that exclusively represent a single object from the overall neuronal activity, to examine the spatiotemporal characteristics of attention in various attentional contexts. First, attention, which is characterized by inhibitory alpha-band (approximately 10 Hz) activity in TRFs, switches between attended and unattended objects every approximately 200 ms, suggesting a sequential sampling even when attention is required to mostly stay on the attended object. Second, the attentional spatiotemporal pattern is modulated by the task context, such that alpha-mediated switching becomes increasingly prominent as the task requires a more uniform distribution of attention. Finally, the switching pattern correlates with attentional behavioral performance. Our work provides direct neural evidence supporting a generally central role of temporal organization mechanism in attention, such that multiple objects are sequentially sorted according to their priority in attentional contexts. The results suggest that selective attention, in addition to the classically posited attentional “focus,” involves a dynamic mechanism for monitoring all objects outside of the focus. Our findings also suggest that attention implements a space (object)-to-time transformation by acting as a series of concatenating attentional chunks that operate on 1 object at a time. PMID:28658261

Synthesis of Polyheteroaromatic Compounds via Rhodium-Catalyzed Multiple C-H Bond Activation and Oxidative Annulation.

PubMed

Peng, Shiyong; Liu, Suna; Zhang, Sai; Cao, Shengyu; Sun, Jiangtao

2015-10-16

Polyheteroaromatic compounds are potential optoelectronic conjugated materials due to their electro- and photochemical properties. Transition-metal-catalyzed multiple C-H activation and sequential oxidative annulation allows rapidly assembling of those compounds from readily available starting materials. A rhodium-catalyzed cascade oxidative annulation of β-enamino esters or 4-aminocoumarins with internal alkynes is described to access those compounds, featuring multiple C-H/N-H bond cleavages and sequential C-C/C-N bond formations in one pot.

ERβ up-regulation was involved in silibinin-induced growth inhibition of human breast cancer MCF-7 cells.

PubMed

Zheng, Nan; Liu, Lu; Liu, Weiwei; Zhang, Ping; Huang, Huai; Zang, Linghe; Hayashi, Toshihiko; Tashiro, Shin-ichi; Onodera, Satoshi; Xia, Mingyu; Ikejima, Takashi

2016-02-01

We previously reported that silibinin induced a loss of cell viability in breast cancer (MCF-7) cells by ERα down-regulation. But whether this cytotoxicity depends on another estrogen receptor, ERβ, has yet to be elucidated. Therefore, we sought to explore the effects of ERβ modulation on cell viability by using an ERβ-selective agonist (Diarylprepionitrile, DPN) and an antagonist (PHTPP). Our data demonstrated that ERβ served as a growth suppressor in MCF-7 cells, and the incubation of silibinin, elevated ERβ expression, resulting in the tumor growth inhibition. The cytotoxic effect of silibinin was diminished by PHTPP and enhanced by DPN. Silencing of ERβ by siRNA confirmed these results. Apoptotic cascades, including the sequential activation of caspase-9 and -6, and finally the cleavage of caspase substrates, PARP and ICAD, caused by treatment with silibinin, were all repressed by PHTPP pre-treatment but exacerbated by DPN. Unlike ERα, ERβ did not involve autophagic process in the regulation, since neither autophagic inhibitor (3-MA) nor the inducer (rapamycin) affected the cell survival rates regardless ERβ activity. Taken together, silibinin induced apoptosis through mitochondrial pathway by up-regulating ERβ pathways in MCF-7 cells without the involvement of autophagy. Copyright © 2016. Published by Elsevier Inc.

Involvement of CYP4F2 in the Metabolism of a Novel Monophosphate Ester Prodrug of Gemcitabine and Its Interaction Potential In Vitro.

PubMed

Wang, Yedong; Li, Yuan; Lu, Jia; Qi, Huixin; Cheng, Isabel; Zhang, Hongjian

2018-05-16

Compound- 3 is an oral monophosphate prodrug of gemcitabine. Previous data showed that Compound- 3 was more potent than gemcitabine and it was orally active in a tumor xenograft model. In the present study, the metabolism of Compound- 3 was investigated in several well-known in vitro matrices. While relatively stable in human and rat plasma, Compound- 3 demonstrated noticeable metabolism in liver and intestinal microsomes in the presence of NADPH and human hepatocytes. Compound- 3 could also be hydrolyzed by alkaline phosphatase, leading to gemcitabine formation. Metabolite identification using accurate mass- and information-based scan techniques revealed that Compound- 3 was subjected to sequential metabolism, forming alcohol, aldehyde and carboxylic acid metabolites, respectively. Results from reaction phenotyping studies indicated that cytochrome P450 4F2 (CYP4F2) was a key CYP isozyme involved in Compound- 3 metabolism. Interaction assays suggested that CYP4F2 activity could be inhibited by Compound- 3 or an antiparasitic prodrug pafuramidine. Because CYP4F2 is a key CYP isozyme involved in the metabolism of eicosanoids and therapeutic drugs, clinical relevance of drug-drug interactions mediated via CYP4F2 inhibition warrants further investigation.

Sequential bilateral cochlear implantation improves working performance, quality of life, and quality of hearing.

PubMed

Härkönen, Kati; Kivekäs, Ilkka; Rautiainen, Markus; Kotti, Voitto; Sivonen, Ville; Vasama, Juha-Pekka

2015-05-01

This prospective study shows that working performance, quality of life (QoL), and quality of hearing (QoH) are better with two compared with a single cochlear implant (CI). The impact of the second CI on the patient's QoL is as significant as the impact of the first CI. To evaluate the benefits of sequential bilateral cochlear implantation in working, QoL, and QoH. We studied working performance, work-related stress, QoL, and QoH with specific questionnaires in 15 patients with unilateral CI scheduled for sequential CI of another ear. Sound localization performance and speech perception in noise were measured with specific tests. All questionnaires and tests were performed before the second CI surgery and 6 and 12 months after its activation. Bilateral CIs increased patients' working performance and their work-related stress and fatigue decreased. Communication with co-workers was easier and patients were more active in their working environment. Sequential bilateral cochlear implantation improved QoL, QoH, sound localization, and speech perception in noise statistically significantly.

Hierarchical interactions between Fnr orthologs allows fine-tuning of transcription in response to oxygen in Herbaspirillum seropedicae

PubMed Central

Batista, Marcelo Bueno; Chandra, Govind; Monteiro, Rose Adele; de Souza, Emanuel Maltempi; Dixon, Ray

2018-01-01

Abstract Bacteria adjust the composition of their electron transport chain (ETC) to efficiently adapt to oxygen gradients. This involves differential expression of various ETC components to optimize energy generation. In Herbaspirillum seropedicae, reprogramming of gene expression in response to oxygen availability is controlled at the transcriptional level by three Fnr orthologs. Here, we characterised Fnr regulons using a combination of RNA-Seq and ChIP-Seq analysis. We found that Fnr1 and Fnr3 directly regulate discrete groups of promoters (Groups I and II, respectively), and that a third group (Group III) is co-regulated by both transcription factors. Comparison of DNA binding motifs between the three promoter groups suggests Group III promoters are potentially co-activated by Fnr3–Fnr1 heterodimers. Specific interaction between Fnr1 and Fnr3, detected in two-hybrid assays, was dependent on conserved residues in their dimerization interfaces, indicative of heterodimer formation in vivo. The requirements for co-activation of the fnr1 promoter, belonging to Group III, suggest either sequential activation by Fnr3 and Fnr1 homodimers or the involvement of Fnr3–Fnr1 heterodimers. Analysis of Fnr proteins with swapped activation domains provides evidence that co-activation by Fnr1 and Fnr3 at Group III promoters optimises interactions with RNA polymerase to fine-tune transcription in response to prevailing oxygen concentrations. PMID:29529262

Hierarchical interactions between Fnr orthologs allows fine-tuning of transcription in response to oxygen in Herbaspirillum seropedicae.

PubMed

Batista, Marcelo Bueno; Chandra, Govind; Monteiro, Rose Adele; de Souza, Emanuel Maltempi; Dixon, Ray

2018-05-04

Bacteria adjust the composition of their electron transport chain (ETC) to efficiently adapt to oxygen gradients. This involves differential expression of various ETC components to optimize energy generation. In Herbaspirillum seropedicae, reprogramming of gene expression in response to oxygen availability is controlled at the transcriptional level by three Fnr orthologs. Here, we characterised Fnr regulons using a combination of RNA-Seq and ChIP-Seq analysis. We found that Fnr1 and Fnr3 directly regulate discrete groups of promoters (Groups I and II, respectively), and that a third group (Group III) is co-regulated by both transcription factors. Comparison of DNA binding motifs between the three promoter groups suggests Group III promoters are potentially co-activated by Fnr3-Fnr1 heterodimers. Specific interaction between Fnr1 and Fnr3, detected in two-hybrid assays, was dependent on conserved residues in their dimerization interfaces, indicative of heterodimer formation in vivo. The requirements for co-activation of the fnr1 promoter, belonging to Group III, suggest either sequential activation by Fnr3 and Fnr1 homodimers or the involvement of Fnr3-Fnr1 heterodimers. Analysis of Fnr proteins with swapped activation domains provides evidence that co-activation by Fnr1 and Fnr3 at Group III promoters optimises interactions with RNA polymerase to fine-tune transcription in response to prevailing oxygen concentrations.

Neurobiology of rodent self-grooming and its value for translational neuroscience

PubMed Central

Kalueff, Allan V.; Stewart, Adam Michael; Song, Cai; Berridge, Kent C.; Graybiel, Ann M.; Fentress, John C.

2016-01-01

Self-grooming is a complex innate behaviour with an evolutionary conserved sequencing pattern and is one of the most frequently performed behavioural activities in rodents. In this Review, we discuss the neurobiology of rodent self-grooming, and we highlight studies of rodent models of neuropsychiatric disorders — including models of autism spectrum disorder and obsessive compulsive disorder — that have assessed self-grooming phenotypes. We suggest that rodent self-grooming may be a useful measure of repetitive behaviour in such models, and therefore of value to translational psychiatry. Assessment of rodent self-grooming may also be useful for understanding the neural circuits that are involved in complex sequential patterns of action. PMID:26675822

An electrophysiological study of the mental rotation of polygons.

PubMed

Pierret, A; Peronnet, F; Thevenet, M

1994-05-09

Reaction times and event-related potentials (ERPs) were recorded during a task requiring subjects to decide whether two sequentially presented polygons had the same shape regardless of differences in orientation. Reaction times increased approximately linearly with angular departure from upright orientation, which suggests that mental rotation was involved in the comparison process. The ERPs showed, between 665 and 1055 ms, a late posterior negativity also increasing with angular disparity from upright, which we assumed to reflect mental rotation. Two other activities were exhibited, from 265 to 665 ms, which may be related either to an evaluation of the stimulus or a predetermination of its orientation, and from 1055 to 1600 ms attributed to the decision process.

Methanol Cannon Demonstrations Revisited.

ERIC Educational Resources Information Center

Dolson, David A.; And Others

1995-01-01

Describes two variations on the traditional methanol cannon demonstration. The first variation is a chain reaction using real metal chains. The second example involves using easily available components to produce sequential explosions that can be musical in nature. (AIM)

In vitro glucose uptake activity of Aegles marmelos and Syzygium cumini by activation of Glut-4, PI3 kinase and PPARgamma in L6 myotubes.

PubMed

Anandharajan, R; Jaiganesh, S; Shankernarayanan, N P; Viswakarma, R A; Balakrishnan, A

2006-06-01

The purpose of the present study is to investigate the effect of methanolic extracts of Aegles marmelos and Syzygium cumini on a battery of targets glucose transporter (Glut-4), peroxisome proliferator activator receptor gamma (PPARgamma) and phosphatidylinositol 3' kinase (PI3 kinase) involved in glucose transport. A. marmelos and S. cumini are anti-diabetic medicinal plants being used in Indian traditional medicine. Different solvent extracts extracted sequentially were analysed for glucose uptake activity at each step and methanol extracts were found to be significantly active at 100ng/ml dose comparable with insulin and rosiglitazone. Elevation of Glut-4, PPARgamma and PI3 kinase by A. marmelos and S. cumini in association with glucose transport supported the up-regulation of glucose uptake. The inhibitory effect of cycloheximide on A. marmelos- and S. cumini-mediated glucose uptake suggested that new protein synthesis is required for the elevated glucose transport. Current observation concludes that methanolic extracts of A. marmelos and S. cumini activate glucose transport in a PI3 kinase-dependent fashion.

In vivo comparison of simultaneous versus sequential injection technique for thermochemical ablation in a porcine model.

PubMed

Cressman, Erik N K; Shenoi, Mithun M; Edelman, Theresa L; Geeslin, Matthew G; Hennings, Leah J; Zhang, Yan; Iaizzo, Paul A; Bischof, John C

2012-01-01

To investigate simultaneous and sequential injection thermochemical ablation in a porcine model, and compare them to sham and acid-only ablation. This IACUC-approved study involved 11 pigs in an acute setting. Ultrasound was used to guide placement of a thermocouple probe and coaxial device designed for thermochemical ablation. Solutions of 10 M acetic acid and NaOH were used in the study. Four injections per pig were performed in identical order at a total rate of 4 mL/min: saline sham, simultaneous, sequential, and acid only. Volume and sphericity of zones of coagulation were measured. Fixed specimens were examined by H&E stain. Average coagulation volumes were 11.2 mL (simultaneous), 19.0 mL (sequential) and 4.4 mL (acid). The highest temperature, 81.3°C, was obtained with simultaneous injection. Average temperatures were 61.1°C (simultaneous), 47.7°C (sequential) and 39.5°C (acid only). Sphericity coefficients (0.83-0.89) had no statistically significant difference among conditions. Thermochemical ablation produced substantial volumes of coagulated tissues relative to the amounts of reagents injected, considerably greater than acid alone in either technique employed. The largest volumes were obtained with sequential injection, yet this came at a price in one case of cardiac arrest. Simultaneous injection yielded the highest recorded temperatures and may be tolerated as well as or better than acid injection alone. Although this pilot study did not show a clear advantage for either sequential or simultaneous methods, the results indicate that thermochemical ablation is attractive for further investigation with regard to both safety and efficacy.

Monitoring lipase/esterase activity by stopped flow in a sequential injection analysis system using p-nitrophenyl butyrate.

PubMed

Pliego, Jorge; Mateos, Juan Carlos; Rodriguez, Jorge; Valero, Francisco; Baeza, Mireia; Femat, Ricardo; Camacho, Rosa; Sandoval, Georgina; Herrera-López, Enrique J

2015-01-27

Lipases and esterases are biocatalysts used at the laboratory and industrial level. To obtain the maximum yield in a bioprocess, it is important to measure key variables, such as enzymatic activity. The conventional method for monitoring hydrolytic activity is to take out a sample from the bioreactor to be analyzed off-line at the laboratory. The disadvantage of this approach is the long time required to recover the information from the process, hindering the possibility to develop control systems. New strategies to monitor lipase/esterase activity are necessary. In this context and in the first approach, we proposed a lab-made sequential injection analysis system to analyze off-line samples from shake flasks. Lipase/esterase activity was determined using p-nitrophenyl butyrate as the substrate. The sequential injection analysis allowed us to measure the hydrolytic activity from a sample without dilution in a linear range from 0.05-1.60 U/mL, with the capability to reach sample dilutions up to 1000 times, a sampling frequency of five samples/h, with a kinetic reaction of 5 min and a relative standard deviation of 8.75%. The results are promising to monitor lipase/esterase activity in real time, in which optimization and control strategies can be designed.

Monitoring Lipase/Esterase Activity by Stopped Flow in a Sequential Injection Analysis System Using p-Nitrophenyl Butyrate

PubMed Central

Pliego, Jorge; Mateos, Juan Carlos; Rodriguez, Jorge; Valero, Francisco; Baeza, Mireia; Femat, Ricardo; Camacho, Rosa; Sandoval, Georgina; Herrera-López, Enrique J.

2015-01-01

Lipases and esterases are biocatalysts used at the laboratory and industrial level. To obtain the maximum yield in a bioprocess, it is important to measure key variables, such as enzymatic activity. The conventional method for monitoring hydrolytic activity is to take out a sample from the bioreactor to be analyzed off-line at the laboratory. The disadvantage of this approach is the long time required to recover the information from the process, hindering the possibility to develop control systems. New strategies to monitor lipase/esterase activity are necessary. In this context and in the first approach, we proposed a lab-made sequential injection analysis system to analyze off-line samples from shake flasks. Lipase/esterase activity was determined using p-nitrophenyl butyrate as the substrate. The sequential injection analysis allowed us to measure the hydrolytic activity from a sample without dilution in a linear range from 0.05–1.60 U/mL, with the capability to reach sample dilutions up to 1000 times, a sampling frequency of five samples/h, with a kinetic reaction of 5 min and a relative standard deviation of 8.75%. The results are promising to monitor lipase/esterase activity in real time, in which optimization and control strategies can be designed. PMID:25633600

Therapeutic effect for liver-metastasized tumor by sequential intravenous injection of anionic polymer and cationic lipoplex of siRNA.

PubMed

Hattori, Yoshiyuki; Arai, Shohei; Kikuchi, Takuto; Ozaki, Kei-Ichi; Kawano, Kumi; Yonemochi, Etsuo

2016-04-01

Previously, we developed a novel siRNA transfer method to the liver by sequential intravenous injection of anionic polymer and cationic liposome/siRNA complex (cationic lipoplex). In this study, we investigated whether siRNA delivered by this sequential injection could significantly suppress mRNA expression of the targeted gene in liver metastasis and inhibit tumor growth. When cationic lipoplex was intravenously injected into mice bearing liver metastasis of human breast tumor MCF-7 at 1 min after intravenous injection of chondroitin sulfate C (CS) or poly-l-glutamic acid (PGA), siRNA was accumulated in tumor-metastasized liver. In terms of a gene silencing effect, sequential injections of CS or PGA plus cationic lipoplex of luciferase siRNA could reduce luciferase activity in liver MCF-7-Luc metastasis. Regarding the side effects, sequential injections of CS plus cationic lipoplex did not exhibit hepatic damage or induction of inflammatory cytokines in serum after repeated injections, but sequential injections of PGA plus cationic lipoplex did. Finally, sequential injections of CS plus cationic lipoplex of protein kinase N3 siRNA could suppress tumor growth in the mice bearing liver metastasis. From these findings, sequential injection of CS and cationic lipoplex of siRNA might be a novel systemic method of delivering siRNA to liver metastasis.

Sequential Injection/Electrochemical Immunoassay for Quantifying the Pesticide Metabolite 3, 5, 6-Trichloro-2-Pyridinol

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

Liu, Guodong; Riechers, Shawn L.; Timchalk, Chuck

2005-12-04

An automated and sensitive sequential injection electrochemical immunoassay was developed to monitor a potential insecticide biomarker, 3, 5, 6-trichloro-2-pyridinol. The current method involved a sequential injection analysis (SIA) system equipped with a thin-layer electrochemical flow cell and permanent magnet, which was used to fix 3,5,6-trichloro-2-pyridinol (TCP) antibody coated magnetic beads (TCP-Ab-MBs) in the reaction zone. After competitive immunoreactions among TCP-Ab-MBs, TCP analyte, and horseradish peroxidase (HRP) labeled TCP, a 3, 3?, 5, 5?-tetramethylbenzidine dihydrochloride and hydrogen peroxide (TMB-H2O2) substrate solution was injected to produce an electroactive enzymatic product. The activity of HRP tracers was monitored by a square wave voltammetricmore » scanning electroactive enzymatic product in the thin-layer flow cell. The voltammetric characteristics of the substrate and the enzymatic product were investigated under batch conditions, and the parameters of the immunoassay were optimized in the SIA system. Under the optimal conditions, the system was used to measure as low as 6 ng L-1 (ppt) TCP, which is around 50-fold lower than the value indicated by the manufacturer of the TCP RaPID Assay? kit (0.25 ug/L, colorimetric detection). The performance of the developed immunoassay system was successfully evaluated on tap water and river water samples spiked with TCP. This technique could be readily used for detecting other environmental contaminants by developing specific antibodies against contaminants and is expected to open new opportunities for environmental and biological monitoring.« less

Perspective on physiological/endocrine and nutritional factors influencing fertility in post-partum dairy cows.

PubMed

Thatcher, W W; Santos, J E P; Silvestre, F T; Kim, I H; Staples, C R

2010-09-01

Increasing reproductive performance of post-partum lactating dairy cows is a multi-factorial challenge involving disciplines of production medicine, nutrition, physiology and herd management. Systems of programmed timed insemination have been fine-tuned to achieve pregnancy per artificial inseminations (AI) approximating 45%. Systems have optimized follicle development, integrated follicle development with timing of induced corpus luteum regression and fine-tuned sequential timing of induced ovulation and AI. Use of programmes for insemination have identified occurrence of anovulatory ovarian status, body condition, uterine health and seasonal summer stress as factors contributing to reduced herd fertility. Furthermore, programmes of timed insemination provide a platform to evaluate efficacy of nutritional and herd health systems targeted to the transition and post-partum periods. The homeorhetic periparturient period, as cows deal with decreases in dry matter intake, results in a negative energy balance and is associated with a period of immunosuppression. Cows that transition well will cycle earlier and have a greater risk of becoming pregnant earlier post-partum. The innate arms of the immune system (acute and adaptive) are suppressed during the periparturient period. Cows experiencing the sequential complex of disorders such as dystocia, puerperal metritis, metritis, endometritis and subclinical endometritis are subsequently less fertile. Targeted strategies of providing specific nutraceuticals that provide pro- and anti-inflammatory effects, such as polyunsaturated fatty acids (e.g., linoleic, eicosapentaenoic/docosahexaenoic, conjugated linoleic acid), sequential glycogenic and lipogenic enrichment of diets, and organic selenium appear to differentially regulate and improve the immune and reproductive systems to benefit an earlier restoration of ovarian activity and increased fertility. © 2010 Blackwell Verlag GmbH.

Sequential dengue virus infections detected in active and passive surveillance programs in Thailand, 1994-2010.

PubMed

Bhoomiboonchoo, Piraya; Nisalak, Ananda; Chansatiporn, Natkamol; Yoon, In-Kyu; Kalayanarooj, Siripen; Thipayamongkolgul, Mathuros; Endy, Timothy; Rothman, Alan L; Green, Sharone; Srikiatkhachorn, Anon; Buddhari, Darunee; Mammen, Mammen P; Gibbons, Robert V

2015-03-14

The effect of prior dengue virus (DENV) exposure on subsequent heterologous infection can be beneficial or detrimental depending on many factors including timing of infection. We sought to evaluate this effect by examining a large database of DENV infections captured by both active and passive surveillance encompassing a wide clinical spectrum of disease. We evaluated datasets from 17 years of hospital-based passive surveillance and nine years of cohort studies, including clinical and subclinical DENV infections, to assess the outcomes of sequential heterologous infections. Chi square or Fisher's exact test was used to compare proportions of infection outcomes such as disease severity; ANOVA was used for continuous variables. Multivariate logistic regression was used to assess risk factors for infection outcomes. Of 38,740 DENV infections, two or more infections were detected in 502 individuals; 14 had three infections. The mean ages at the time of the first and second detected infections were 7.6 ± 3.0 and 11.2 ± 3.0 years. The shortest time between sequential infections was 66 days. A longer time interval between sequential infections was associated with dengue hemorrhagic fever (DHF) in the second detected infection (OR 1.3, 95% CI 1.2-1.4). All possible sequential serotype pairs were observed among 201 subjects with DHF at the second detected infection, except DENV-4 followed by DENV-3. Among DENV infections detected in cohort subjects by active study surveillance and subsequent non-study hospital-based passive surveillance, hospitalization at the first detected infection increased the likelihood of hospitalization at the second detected infection. Increasing time between sequential DENV infections was associated with greater severity of the second detected infection, supporting the role of heterotypic immunity in both protection and enhancement. Hospitalization was positively associated between the first and second detected infections, suggesting a possible predisposition in some individuals to more severe dengue disease.

Radiofrequency catheter ablation of idiopathic ventricular arrhythmias originating from intramural foci in the left ventricular outflow tract: efficacy of sequential versus simultaneous unipolar catheter ablation.

PubMed

Yamada, Takumi; Maddox, William R; McElderry, H Thomas; Doppalapudi, Harish; Plumb, Vance J; Kay, G Neal

2015-04-01

Idiopathic ventricular arrhythmias (VAs) originating from the left ventricular outflow tract (LVOT) sometimes require catheter ablation from the endocardial and epicardial sides for their elimination, suggesting the presence of intramural VA foci. This study investigated the efficacy of sequential and simultaneous unipolar radiofrequency catheter ablation from the endocardial and epicardial sides in treating intramural LVOT VAs. Fourteen consecutive LVOT VAs, which required sequential or simultaneous irrigated unipolar radiofrequency ablation from the endocardial and epicardial sides for their elimination, were studied. The first ablation was performed at the site with the earliest local ventricular activation and best pace map on the endocardial or epicardial side. When the first ablation was unsuccessful, the second ablation was delivered on the other surface. If this sequential unipolar ablation failed, simultaneous unipolar ablation from both sides was performed. The first ablation was performed on the epicardial side in 9 VAs and endocardial side in 5 VAs. The intramural LVOT VAs were successfully eliminated by the sequential (n=9) or simultaneous (n=5) unipolar catheter ablation. Simultaneous ablation was most likely to be required for the elimination of the VAs when the distance between the endocardial and epicardial ablation sites was >8 mm and the earliest local ventricular activation time relative to the QRS onset during the VAs of <-30 ms was recorded at those ablation sites. LVOT VAs originating from intramural foci could usually be eliminated by sequential unipolar radiofrequency ablation and sometimes required simultaneous ablation from both the endocardial and epicardial sides. © 2015 American Heart Association, Inc.

Sequential cancer immunotherapy: targeted activity of dimeric TNF and IL-8

PubMed Central

Adrian, Nicole; Siebenborn, Uta; Fadle, Natalie; Plesko, Margarita; Fischer, Eliane; Wüest, Thomas; Stenner, Frank; Mertens, Joachim C.; Knuth, Alexander; Ritter, Gerd; Old, Lloyd J.; Renner, Christoph

2009-01-01

Polymorphonuclear neutrophils (PMNs) are potent effectors of inflammation and their attempts to respond to cancer are suggested by their systemic, regional and intratumoral activation. We previously reported on the recruitment of CD11b+ leukocytes due to tumor site-specific enrichment of TNF activity after intravenous administration of a dimeric TNF immunokine with specificity for fibroblast activation protein (FAP). However, TNF-induced chemo-attraction and extravasation of PMNs from blood into the tumor is a multistep process essentially mediated by interleukin 8. With the aim to amplify the TNF-induced and IL-8-mediated chemotactic response, we generated immunocytokines by N-terminal fusion of a human anti-FAP scFv fragment with human IL-8 (IL-872) and its N-terminally truncated form IL-83-72. Due to the dramatic difference in chemotaxis induction in vitro, we favored the mature chemokine fused to the anti-FAP scFv for further investigation in vivo. BALB/c nu/nu mice were simultaneously xenografted with FAP-positive or -negative tumors and extended chemo-attraction of PMNs was only detectable in FAP-expressing tissue after intravenous administration of the anti-FAP scFv-IL-872 construct. As TNF-activated PMNs are likewise producers and primary targets for IL-8, we investigated the therapeutic efficacy of co-administration of both effectors: Sequential application of scFv-IL-872 and dimeric IgG1-TNF fusion proteins significantly enhanced anti-tumor activity when compared either to a single effector treatment regimen or sequential application of non-targeted cytokines, indicating that the tumor-restricted sequential application of IL-872 and TNF is a promising approach for cancer therapy. PMID:19267427

Can sequential parallel comparison design and two-way enriched design be useful in medical device clinical trials?

PubMed

Ivanova, Anastasia; Zhang, Zhiwei; Thompson, Laura; Yang, Ying; Kotz, Richard M; Fang, Xin

2016-01-01

Sequential parallel comparison design (SPCD) was proposed for trials with high placebo response. In the first stage of SPCD subjects are randomized between placebo and active treatment. In the second stage placebo nonresponders are re-randomized between placebo and active treatment. Data from the population of "all comers" and the subpopulations of placebo nonresponders then combined to yield a single p-value for treatment comparison. Two-way enriched design (TED) is an extension of SPCD where active treatment responders are also re-randomized between placebo and active treatment in Stage 2. This article investigates the potential uses of SPCD and TED in medical device trials.

Alexia and agraphia with lesions of the angular and supramarginal gyri: evidence for the disruption of sequential processing.

PubMed

Sakurai, Yasuhisa; Asami, Masahiko; Mannen, Toru

2010-01-15

To determine the features of alexia or agraphia with a left angular or supramarginal gyrus lesion. We assessed the reading and writing abilities of three patients using kanji (Japanese morphograms) and kana (Japanese syllabograms). Patient 1 showed kana alexia and kanji agraphia following a hemorrhage in the left angular gyrus and the adjacent lateral occipital gyri. Patient 2 presented with minimal pure agraphia for both kanji and kana after an infarction in the left angular gyrus involving part of the supramarginal gyrus. Patient 3 also showed moderate pure agraphia for both kanji and kana after an infarction in the left supramarginal and postcentral gyri. All three patients made transposition errors (changing of sequential order of kana characters) in reading. Patient 1 showed letter-by-letter reading and a word-length effect and made substitution errors (changing hiragana [one form of kana] characters in a word to katakana [another form of kana] characters and vice versa) in writing. Alexia occurs as "angular" alexia only when the lesion involves the adjacent lateral occipital gyri. Transposition errors suggest disrupted sequential phonological processing from the angular and lateral occipital gyri to the supramarginal gyrus. Substitution errors suggest impaired allographic conversion between hiragana and katakana attributable to a dysfunction in the angular/lateral occipital gyri.

One-pot multienzyme (OPME) systems for chemoenzymatic synthesis of carbohydrates

PubMed Central

Yu, Hai; Chen, Xi

2016-01-01

Glycosyltransferase-catalyzed enzymatic and chemoenzymatic syntheses are powerful approaches for the production of oligosaccharides, polysaccharides, glycoconjugates, and their derivatives. Enzymes involved in the biosynthesis of sugar nucleotide donors can be combined with the glycosyltransferases in one pot for efficient production of target glycans from simple monosaccharides and accpetors. The identification of enzymes involved in the salvage pathway of sugar nucleotide generation has greatly facilitate the development of simplified and efficient one-pot multienzyme (OPME) systems for synthesizing major glycan epitopes in mammalian glycomes. The applications of OPME methods are steadily gaining popularity mainly due to the increasing availability of wild-type and engineered enzymes. Substrate promiscuity of these enzymes and their mutants allows OPME synthesis of carbohydrates with naturally occurring post-glycosylational modificiation (PGMs) and their non-natural derivatives using modified monosaccharides as precursors. The OPME systems can be applied in sequential for synthesizing complex carbohydrates. The sequence of the sequential OPME processes, the glycosyltransferase used, and the substrate specificities of glycosyltransferasese define the structures of the products. The OPME and sequential OPME strategies can be extended to diverse glycans in other glycomes when suitable enzymes with substrate promiscuity become available. The Perspective summariezes the work of the authors and collaborators on the development of glycosyltransferase-based OPME systems for carbohydrate synthesis. Future directions are also discussed. PMID:26881499

Spatiotemporal Distribution of Location and Object Effects in Primary Motor Cortex Neurons during Reach-to-Grasp

PubMed Central

Rouse, Adam G.

2016-01-01

Reaching and grasping typically are considered to be spatially separate processes that proceed concurrently in the arm and the hand, respectively. The proximal representation in the primary motor cortex (M1) controls the arm for reaching, while the distal representation controls the hand for grasping. Many studies of M1 activity therefore have focused either on reaching to various locations without grasping different objects, or else on grasping different objects all at the same location. Here, we recorded M1 neurons in the anterior bank and lip of the central sulcus as monkeys performed more naturalistic movements, reaching toward, grasping, and manipulating four different objects in up to eight different locations. We quantified the extent to which variation in firing rates depended on location, on object, and on their interaction—all as a function of time. Activity proceeded largely in two sequential phases: the first related predominantly to the location to which the upper extremity reached, and the second related to the object about to be grasped. Both phases involved activity distributed widely throughout the sampled territory, spanning both the proximal and the distal upper extremity representation in caudal M1. Our findings indicate that naturalistic reaching and grasping, rather than being spatially segregated processes that proceed concurrently, each are spatially distributed processes controlled by caudal M1 in large part sequentially. Rather than neuromuscular processes separated in space but not time, reaching and grasping are separated more in time than in space. SIGNIFICANCE STATEMENT Reaching and grasping typically are viewed as processes that proceed concurrently in the arm and hand, respectively. The arm region in the primary motor cortex (M1) is assumed to control reaching, while the hand region controls grasping. During naturalistic reach–grasp–manipulate movements, we found, however, that neuron activity proceeds largely in two sequential phases, each spanning both arm and hand representations in M1. The first phase is related predominantly to the reach location, and the second is related to the object about to be grasped. Our findings indicate that reaching and grasping are successive aspects of a single movement. Initially the arm and the hand both are projected toward the object's location, and later both are shaped to grasp and manipulate. PMID:27733614

First-Episode Psychosis and the Criminal Justice System: Using a Sequential Intercept Framework to Highlight Risks and Opportunities.

PubMed

Wasser, Tobias; Pollard, Jessica; Fisk, Deborah; Srihari, Vinod

2017-10-01

In first-episode psychosis there is a heightened risk of aggression and subsequent criminal justice involvement. This column reviews the evidence pointing to these heightened risks and highlights opportunities, using a sequential intercept model, for collaboration between mental health services and existing diversionary programs, particularly for patients whose behavior has already brought them to the attention of the criminal justice system. Coordinating efforts in these areas across criminal justice and clinical spheres can decrease the caseload burden on the criminal justice system and optimize clinical and legal outcomes for this population.

Optimal trajectories for aeroassisted orbital transfer

NASA Technical Reports Server (NTRS)

Miele, A.; Venkataraman, P.

1983-01-01

Consideration is given to classical and minimax problems involved in aeroassisted transfer from high earth orbit (HEO) to low earth orbit (LEO). The transfer is restricted to coplanar operation, with trajectory control effected by means of lift modulation. The performance of the maneuver is indexed to the energy expenditure or, alternatively, the time integral of the heating rate. Firist-order optimality conditions are defined for the classical approach, as are a sequential gradient-restoration algorithm and a combined gradient-restoration algorithm. Minimization techniques are presented for the aeroassisted transfer energy consumption and time-delay integral of the heating rate, as well as minimization of the pressure. It is shown that the eigenvalues of the Jacobian matrix of the differential system is both stiff and unstable, implying that the sequential gradient restoration algorithm in its present version is unsuitable. A new method, involving a multipoint approach to the two-poing boundary value problem, is recommended.

[Reflex epilepsy evoked by decision making: report of a case (author's transl)].

PubMed

Mutani, R; Ganga, A; Agnetti, V

1980-01-01

A 17-year-old girl with a story of Gran Mal attacks occurring during lessons of mathematics or solving mathematical problems, was investigated with prolonged EEG recordings. During the sessions, relax periods were alternated with arithmetical or mathematical testing, with card or checkers games and solution of puzzles and crossword problems, and with different neuropsychological tests. EGG recordings were characterized by the appearance, on a normal background, of bilaterally synchronous and symmetrical spike-and-wave and polispike-and-wave discharges, associated with loss of consciousness. During relax their mean frequency was one/54 min., it doubled during execution of tests involved with nonsequential decision making, and was eight times as high (one/7 min.) during tests involving sequential decision making. Some tension, challenge and complexity of the performance were also important as precipitating factors. Their lack deprived sequential tests of their efficacy, while on the contrary their presence sometimes gave nonsequential tests full efficacy.

Bursts and heavy tails in temporal and sequential dynamics of foraging decisions.

PubMed

Jung, Kanghoon; Jang, Hyeran; Kralik, Jerald D; Jeong, Jaeseung

2014-08-01

A fundamental understanding of behavior requires predicting when and what an individual will choose. However, the actual temporal and sequential dynamics of successive choices made among multiple alternatives remain unclear. In the current study, we tested the hypothesis that there is a general bursting property in both the timing and sequential patterns of foraging decisions. We conducted a foraging experiment in which rats chose among four different foods over a continuous two-week time period. Regarding when choices were made, we found bursts of rapidly occurring actions, separated by time-varying inactive periods, partially based on a circadian rhythm. Regarding what was chosen, we found sequential dynamics in affective choices characterized by two key features: (a) a highly biased choice distribution; and (b) preferential attachment, in which the animals were more likely to choose what they had previously chosen. To capture the temporal dynamics, we propose a dual-state model consisting of active and inactive states. We also introduce a satiation-attainment process for bursty activity, and a non-homogeneous Poisson process for longer inactivity between bursts. For the sequential dynamics, we propose a dual-control model consisting of goal-directed and habit systems, based on outcome valuation and choice history, respectively. This study provides insights into how the bursty nature of behavior emerges from the interaction of different underlying systems, leading to heavy tails in the distribution of behavior over time and choices.

Addressing Challenges in Web Accessibility for the Blind and Visually Impaired

ERIC Educational Resources Information Center

Guercio, Angela; Stirbens, Kathleen A.; Williams, Joseph; Haiber, Charles

2011-01-01

Searching for relevant information on the web is an important aspect of distance learning. This activity is a challenge for visually impaired distance learners. While sighted people have the ability to filter information in a fast and non sequential way, blind persons rely on tools that process the information in a sequential way. Learning is…

Predictive Movements and Human Reinforcement Learning of Sequential Action

ERIC Educational Resources Information Center

de Kleijn, Roy; Kachergis, George; Hommel, Bernhard

2018-01-01

Sequential action makes up the bulk of human daily activity, and yet much remains unknown about how people learn such actions. In one motor learning paradigm, the serial reaction time (SRT) task, people are taught a consistent sequence of button presses by cueing them with the next target response. However, the SRT task only records keypress…

Effective Identification of Similar Patients Through Sequential Matching over ICD Code Embedding.

PubMed

Nguyen, Dang; Luo, Wei; Venkatesh, Svetha; Phung, Dinh

2018-04-11

Evidence-based medicine often involves the identification of patients with similar conditions, which are often captured in ICD (International Classification of Diseases (World Health Organization 2013)) code sequences. With no satisfying prior solutions for matching ICD-10 code sequences, this paper presents a method which effectively captures the clinical similarity among routine patients who have multiple comorbidities and complex care needs. Our method leverages the recent progress in representation learning of individual ICD-10 codes, and it explicitly uses the sequential order of codes for matching. Empirical evaluation on a state-wide cancer data collection shows that our proposed method achieves significantly higher matching performance compared with state-of-the-art methods ignoring the sequential order. Our method better identifies similar patients in a number of clinical outcomes including readmission and mortality outlook. Although this paper focuses on ICD-10 diagnosis code sequences, our method can be adapted to work with other codified sequence data.

A sequential EMT-MET mechanism drives the differentiation of human embryonic stem cells towards hepatocytes.

PubMed

Li, Qiuhong; Hutchins, Andrew P; Chen, Yong; Li, Shengbiao; Shan, Yongli; Liao, Baojian; Zheng, Dejin; Shi, Xi; Li, Yinxiong; Chan, Wai-Yee; Pan, Guangjin; Wei, Shicheng; Shu, Xiaodong; Pei, Duanqing

2017-05-03

Reprogramming has been shown to involve EMT-MET; however, its role in cell differentiation is unclear. We report here that in vitro differentiation of hESCs to hepatic lineage undergoes a sequential EMT-MET with an obligatory intermediate mesenchymal phase. Gene expression analysis reveals that Activin A-induced formation of definitive endoderm (DE) accompanies a synchronous EMT mediated by autocrine TGFβ signalling followed by a MET process. Pharmacological inhibition of TGFβ signalling blocks the EMT as well as DE formation. We then identify SNAI1 as the key EMT transcriptional factor required for the specification of DE. Genetic ablation of SNAI1 in hESCs does not affect the maintenance of pluripotency or neural differentiation, but completely disrupts the formation of DE. These results reveal a critical mesenchymal phase during the acquisition of DE, highlighting a role for sequential EMT-METs in both differentiation and reprogramming.

Two-step sequential pretreatment for the enhanced enzymatic hydrolysis of coffee spent waste.

PubMed

Ravindran, Rajeev; Jaiswal, Swarna; Abu-Ghannam, Nissreen; Jaiswal, Amit K

2017-09-01

In the present study, eight different pretreatments of varying nature (physical, chemical and physico-chemical) followed by a sequential, combinatorial pretreatment strategy was applied to spent coffee waste to attain maximum sugar yield. Pretreated samples were analysed for total reducing sugar, individual sugars and generation of inhibitory compounds such as furfural and hydroxymethyl furfural (HMF) which can hinder microbial growth and enzyme activity. Native spent coffee waste was high in hemicellulose content. Galactose was found to be the predominant sugar in spent coffee waste. Results showed that sequential pretreatment yielded 350.12mg of reducing sugar/g of substrate, which was 1.7-fold higher than in native spent coffee waste (203.4mg/g of substrate). Furthermore, extensive delignification was achieved using sequential pretreatment strategy. XRD, FTIR, and DSC profiles of the pretreated substrates were studied to analyse the various changes incurred in sequentially pretreated spent coffee waste as opposed to native spent coffee waste. Copyright © 2017 Elsevier Ltd. All rights reserved.

Consecutive pharmacological activation of PKA and PKC mimics the potent cardioprotection of temperature preconditioning

PubMed Central

Khaliulin, Igor; Parker, Joanna E.; Halestrap, Andrew P.

2010-01-01

Aims Temperature preconditioning (TP) provides very powerful protection against ischaemia/reperfusion. Understanding the signalling pathways involved may enable the development of effective pharmacological cardioprotection. We investigated the interrelationship between activation of protein kinase A (PKA) and protein kinase C (PKC) in the signalling mechanisms of TP and developed a potent pharmacological intervention based on this mechanism. Methods and results Isolated rat hearts were subjected to TP, 30 min global ischaemia, and 60 min reperfusion. Other control and TP hearts were perfused with either sotalol (β-adrenergic blocker) or H-89 (PKA inhibitor). Some hearts were pre-treated with either isoproterenol (β-adrenergic agonist) or adenosine (PKC activator) that were given alone, simultaneously, or sequentially. Pre-treatment with isoproterenol, adenosine, and the consecutive isoproterenol/adenosine treatment was also combined with the PKC inhibitor chelerythrine. Cardioprotection was evaluated by haemodynamic function recovery, lactate dehydrogenase release, measurement of mitochondrial permeability transition pore opening, and protein carbonylation during reperfusion. Cyclic AMP and PKA activity were increased in TP hearts. H-89 and sotalol blocked the cardioprotective effect of TP and TP-induced PKC activation. Isoproterenol, adenosine, and the consecutive treatment increased PKC activity during pre-ischaemia. Isoproterenol significantly reduced myocardial glycogen content. Isoproterenol and adenosine, alone or simultaneously, protected hearts but the consecutive treatment gave the highest protection. Cardioprotective effects of adenosine were completely blocked by chelerythrine but those of the consecutive treatment only attenuated. Conclusion The signal transduction pathway of TP involves PKA activation that precedes PKC activation. Pharmacologically induced consecutive PKA/PKC activation mimics TP and induces extremely potent cardioprotection. PMID:20558443

The activation of human endogenous retrovirus K (HERV-K) is implicated in melanoma cell malignant transformation

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

Serafino, A.; Balestrieri, E.; Pierimarchi, P.

2009-03-10

Melanoma development is a multi-step process arising from a series of genetic and epigenetic events. Although the sequential stages involved in progression from melanocytes to malignant melanoma are clearly defined, our current understanding of the mechanisms leading to melanoma onset is still incomplete. Growing evidence show that the activation of endogenous retroviral sequences might be involved in transformation of melanocytes as well as in the increased ability of melanoma cells to escape immune surveillance. Here we show that human melanoma cells in vitro undergo a transition from adherent to a more malignant, non-adherent phenotype when exposed to stress conditions. Melanoma-derivedmore » non-adherent cells are characterized by an increased proliferative potential and a decreased expression of both HLA class I molecules and Melan-A/MART-1 antigen, similarly to highly malignant cells. These phenotypic and functional modifications are accompanied by the activation of human endogenous retrovirus K expression (HERV-K) and massive production of viral-like particles. Down-regulation of HERV-K expression by RNA interference prevents the transition from the adherent to the non-adherent growth phenotype in low serum. These results implicate HERV-K in at least some critical steps of melanoma progression.« less

Patients with Parkinson's Disease Learn to Control Complex Systems via Procedural as Well as Non-Procedural Learning

ERIC Educational Resources Information Center

Osman, Magda; Wilkinson, Leonora; Beigi, Mazda; Castaneda, Cristina Sanchez; Jahanshahi, Marjan

2008-01-01

The striatum is considered to mediate some forms of procedural learning. Complex dynamic control (CDC) tasks involve an individual having to make a series of sequential decisions to achieve a specific outcome (e.g. learning to operate and control a car), and they involve procedural learning. The aim of this study was to test the hypothesis that…

Movement of particles using sequentially activated dielectrophoretic particle trapping

DOEpatents

Miles, Robin R.

2004-02-03

Manipulation of DNA and cells/spores using dielectrophoretic (DEP) forces to perform sample preparation protocols for polymerized chain reaction (PCR) based assays for various applications. This is accomplished by movement of particles using sequentially activated dielectrophoretic particle trapping. DEP forces induce a dipole in particles, and these particles can be trapped in non-uniform fields. The particles can be trapped in the high field strength region of one set of electrodes. By switching off this field and switching on an adjacent electrodes, particles can be moved down a channel with little or no flow.

Comparison of human embryomorphokinetic parameters in sequential or global culture media.

PubMed

Kazdar, Nadia; Brugnon, Florence; Bouche, Cyril; Jouve, Guilhem; Veau, Ségolène; Drapier, Hortense; Rousseau, Chloé; Pimentel, Céline; Viard, Patricia; Belaud-Rotureau, Marc-Antoine; Ravel, Célia

2017-08-01

A prospective study on randomized patients was conducted to determine how morphokinetic parameters are altered in embryos grown in sequential versus global culture media. Eleven morphokinetic parameters of 160 single embryos transferred were analyzed by time lapse imaging involving two University-affiliated in vitro fertilization (IVF) centers. We found that the fading of the two pronuclei occurred earlier in global (22.56±2.15 hpi) versus sequential media (23.63±2.71 hpi; p=0.0297). Likewise, the first cleavage started earlier at 24.52±2.33 hpi vs 25.76±2.95 hpi (p=0.0158). Also, the first cytokinesis was shorter in global medium, lasting 18±10.2 minutes in global versus 36±37.8 minutes in sequential culture medium (p <0.0001). We also observed a significant shortening in the duration of the 2-cell stage in sequential medium: 10.64 h±2.75 versus 11.66 h±1.11 in global medium (p=0.0225) which suggested a faster progression of the embryos through their first mitotic cell cycle. In conclusion, morphokinetic analysis of human embryos by Time lapse imaging reveals significant differences in five kinetic variables according to culture medium. Our study highlights the need to adapt morphokinetic analysis accordingly to the type of media used to best support human early embryo development.

Students' conceptual performance on synthesis physics problems with varying mathematical complexity

NASA Astrophysics Data System (ADS)

Ibrahim, Bashirah; Ding, Lin; Heckler, Andrew F.; White, Daniel R.; Badeau, Ryan

2017-06-01

A body of research on physics problem solving has focused on single-concept problems. In this study we use "synthesis problems" that involve multiple concepts typically taught in different chapters. We use two types of synthesis problems, sequential and simultaneous synthesis tasks. Sequential problems require a consecutive application of fundamental principles, and simultaneous problems require a concurrent application of pertinent concepts. We explore students' conceptual performance when they solve quantitative synthesis problems with varying mathematical complexity. Conceptual performance refers to the identification, follow-up, and correct application of the pertinent concepts. Mathematical complexity is determined by the type and the number of equations to be manipulated concurrently due to the number of unknowns in each equation. Data were collected from written tasks and individual interviews administered to physics major students (N =179 ) enrolled in a second year mechanics course. The results indicate that mathematical complexity does not impact students' conceptual performance on the sequential tasks. In contrast, for the simultaneous problems, mathematical complexity negatively influences the students' conceptual performance. This difference may be explained by the students' familiarity with and confidence in particular concepts coupled with cognitive load associated with manipulating complex quantitative equations. Another explanation pertains to the type of synthesis problems, either sequential or simultaneous task. The students split the situation presented in the sequential synthesis tasks into segments but treated the situation in the simultaneous synthesis tasks as a single event.

Engineered biosealant producing inorganic and organic biopolymers

USDA-ARS?s Scientific Manuscript database

Microbiologically induced calcium carbonate precipitation (MICCP) is a naturally occurring biological process that has shown its potential in remediation of a wide range of structural damages including concrete cracks. MICCP involves sequential microbiological and chemical reactions, such as urea h...

Role of mitochondrial processing peptidase and AAA proteases in processing of the yeast acetohydroxyacid synthase precursor.

PubMed

Dasari, Suvarna; Kölling, Ralf

2016-07-01

We studied presequence processing of the mitochondrial-matrix targeted acetohydroxyacid synthase (Ilv2). C-terminal 3HA-tagging altered the cleavage pattern from a single step to sequential two-step cleavage, giving rise to two Ilv2-3HA forms (A and B). Both cleavage events were dependent on the mitochondrial processing peptidase (MPP). We present evidence for the involvement of three AAA ATPases, m- and i-AAA proteases, and Mcx1, in Ilv2-3HA processing. Both, precursor to A-form and A-form to B-form cleavage were strongly affected in a ∆yme1 mutant. These defects could be suppressed by overexpression of MPP, suggesting that MPP activity is limiting in the ∆yme1 mutant. Our data suggest that for some substrates AAA ATPases could play an active role in the translocation of matrix-targeted proteins.

Sequential biodegradation of TNT, RDX and HMX in a mixture.

PubMed

Sagi-Ben Moshe, S; Ronen, Z; Dahan, O; Weisbrod, N; Groisman, L; Adar, E; Nativ, R

2009-01-01

We describe TNT's inhibition of RDX and HMX anaerobic degradation in contaminated soil containing indigenous microbial populations. Biodegradation of RDX or HMX alone was markedly faster than their degradation in a mixture with TNT, implying biodegradation inhibition by the latter. The delay caused by the presence of TNT continued even after its disappearance and was linked to the presence of its intermediate, tetranitroazoxytoluene. PCR-DGGE analysis of cultures derived from the soil indicated a clear reduction in microbial biomass and diversity with increasing TNT concentration. At high-TNT concentrations (30 and 90 mg/L), only a single band, related to Clostridium nitrophenolicum, was observed after 3 days of incubation. We propose that the mechanism of TNT inhibition involves a cytotoxic effect on the RDX- and HMX-degrading microbial population. TNT inhibition in the top active soil can therefore initiate rapid transport of RDX and HMX to the less active subsurface and groundwater.

Evaluation of sequential extraction procedures for soluble and insoluble hexavalent chromium compounds in workplace air samples.

PubMed

Ashley, Kevin; Applegate, Gregory T; Marcy, A Dale; Drake, Pamela L; Pierce, Paul A; Carabin, Nathalie; Demange, Martine

2009-02-01

Because toxicities may differ for Cr(VI) compounds of varying solubility, some countries and organizations have promulgated different occupational exposure limits (OELs) for soluble and insoluble hexavalent chromium (Cr(VI)) compounds, and analytical methods are needed to determine these species in workplace air samples. To address this need, international standard methods ASTM D6832 and ISO 16740 have been published that describe sequential extraction techniques for soluble and insoluble Cr(VI) in samples collected from occupational settings. However, no published performance data were previously available for these Cr(VI) sequential extraction procedures. In this work, the sequential extraction methods outlined in the relevant international standards were investigated. The procedures tested involved the use of either deionized water or an ammonium sulfate/ammonium hydroxide buffer solution to target soluble Cr(VI) species. This was followed by extraction in a sodium carbonate/sodium hydroxide buffer solution to dissolve insoluble Cr(VI) compounds. Three-step sequential extraction with (1) water, (2) sulfate buffer and (3) carbonate buffer was also investigated. Sequential extractions were carried out on spiked samples of soluble, sparingly soluble and insoluble Cr(VI) compounds, and analyses were then generally carried out by using the diphenylcarbazide method. Similar experiments were performed on paint pigment samples and on airborne particulate filter samples collected from stainless steel welding. Potential interferences from soluble and insoluble Cr(III) compounds, as well as from Fe(II), were investigated. Interferences from Cr(III) species were generally absent, while the presence of Fe(II) resulted in low Cr(VI) recoveries. Two-step sequential extraction of spiked samples with (first) either water or sulfate buffer, and then carbonate buffer, yielded quantitative recoveries of soluble Cr(VI) and insoluble Cr(VI), respectively. Three-step sequential extraction gave excessively high recoveries of soluble Cr(VI), low recoveries of sparingly soluble Cr(VI), and quantitative recoveries of insoluble Cr(VI). Experiments on paint pigment samples using two-step extraction with water and carbonate buffer yielded varying percentages of relative fractions of soluble and insoluble Cr(VI). Sequential extractions of stainless steel welding fume air filter samples demonstrated the predominance of soluble Cr(VI) compounds in such samples. The performance data obtained in this work support the Cr(VI) sequential extraction procedures described in the international standards.

Irisin Inhibits Hepatic Cholesterol Synthesis via AMPK-SREBP2 Signaling

PubMed Central

Tang, Hong; Yu, Ruili; Liu, Shiying; Huwatibieke, Bahetiyaer; Li, Ziru; Zhang, Weizhen

2016-01-01

Irisin, a myokine released during exercise, promotes browning of subcutaneous adipose tissue and regulates energy homeostasis. Although exercise constantly reduces blood cholesterol, whether irisin is involved in the regulation of cholesterol remains largely unknown. In the present study, subcutaneous infusion of irisin for 2 weeks induced a reduction in plasma and hepatic cholesterol in high fat diet-induced obese (DIO) mice. These alterations were associated with an activation of 5′ AMP-activated protein kinase (AMPK) and inhibition of sterol regulatory element-binding transcription factor 2 (SREBP2) transcription and nuclear translocation. In primary hepatocytes from either lean or DIO mice, irisin significantly decreased cholesterol content via sequential activation of AMPK and inhibition of SREBP2. Suppression of AMPK by compound C or AMPKα1 siRNA blocked irisin-induced alterations in cholesterol contents and SREBP2. In conclusion, irisin could suppress hepatic cholesterol production via a mechanism dependent of AMPK and SREBP2 signaling. These findings suggest that irisin is a promising therapeutic target for treatment of hypercholesterolemia. PMID:27211556

A need for the standardization of the pharmaceutical sector in Libya

PubMed Central

Mustafa, Asma Abubakr; Kowalski, Stefan Robert

2010-01-01

Medicines are health technologies that can translate into tangible benefits for numerous acute as well as chronic health conditions. A nation's pharmaceutical sector needs to be appropriately structured and managed in order to ensure a safe, effective and quality supply of medicines to society. The process of medicines management involves the sequential management of five critical activity areas; namely; registration, selection, procurement, distribution and use. Formalized and standardized management of all five critical activity areas positively influences the availability, quality and affordability of medicines and ultimately increases the reliability and quality of the national healthcare system. Aim The aim of this review is to examine the current structure and operation of medicines management (i.e. the pharmaceutical sector) in Libya. Conclusion In the Libyan healthcare system all five critical activity areas are compromised. Restructuring of the pharmaceutical sector in Libya is required in order to provide and sustain sound pharmaceutical services for Libyan society and improve the national public health outcomes. PMID:21483563

Linear models of activation cascades: analytical solutions and coarse-graining of delayed signal transduction

PubMed Central

Desikan, Radhika

2016-01-01

Cellular signal transduction usually involves activation cascades, the sequential activation of a series of proteins following the reception of an input signal. Here, we study the classic model of weakly activated cascades and obtain analytical solutions for a variety of inputs. We show that in the special but important case of optimal gain cascades (i.e. when the deactivation rates are identical) the downstream output of the cascade can be represented exactly as a lumped nonlinear module containing an incomplete gamma function with real parameters that depend on the rates and length of the cascade, as well as parameters of the input signal. The expressions obtained can be applied to the non-identical case when the deactivation rates are random to capture the variability in the cascade outputs. We also show that cascades can be rearranged so that blocks with similar rates can be lumped and represented through our nonlinear modules. Our results can be used both to represent cascades in computational models of differential equations and to fit data efficiently, by reducing the number of equations and parameters involved. In particular, the length of the cascade appears as a real-valued parameter and can thus be fitted in the same manner as Hill coefficients. Finally, we show how the obtained nonlinear modules can be used instead of delay differential equations to model delays in signal transduction. PMID:27581482

Cardiac conduction velocity estimation from sequential mapping assuming known Gaussian distribution for activation time estimation error.

PubMed

Shariat, Mohammad Hassan; Gazor, Saeed; Redfearn, Damian

2016-08-01

In this paper, we study the problem of the cardiac conduction velocity (CCV) estimation for the sequential intracardiac mapping. We assume that the intracardiac electrograms of several cardiac sites are sequentially recorded, their activation times (ATs) are extracted, and the corresponding wavefronts are specified. The locations of the mapping catheter's electrodes and the ATs of the wavefronts are used here for the CCV estimation. We assume that the extracted ATs include some estimation errors, which we model with zero-mean white Gaussian noise values with known variances. Assuming stable planar wavefront propagation, we derive the maximum likelihood CCV estimator, when the synchronization times between various recording sites are unknown. We analytically evaluate the performance of the CCV estimator and provide its mean square estimation error. Our simulation results confirm the accuracy of the proposed method and the error analysis of the proposed CCV estimator.

Sequential activation of CD8+ T cells in the draining lymph nodes in response to pulmonary virus infection.

PubMed

Yoon, Heesik; Legge, Kevin L; Sung, Sun-sang J; Braciale, Thomas J

2007-07-01

We have used a TCR-transgenic CD8+ T cell adoptive transfer model to examine the tempo of T cell activation and proliferation in the draining lymph nodes (DLN) in response to respiratory virus infection. The T cell response in the DLN differed for mice infected with different type A influenza strains with the onset of T cell activation/proliferation to the A/JAPAN virus infection preceding the A/PR8 response by 12-24 h. This difference in T cell activation/proliferation correlated with the tempo of accelerated respiratory DC (RDC) migration from the infected lungs to the DLN in response to influenza virus infection, with the migrant RDC responding to the A/JAPAN infection exhibiting a more rapid accumulation in the lymph nodes (i.e., peak migration for A/JAPAN at 18 h, A/PR8 at 24-36 h). Furthermore, in vivo administration of blocking anti-CD62L Ab at various time points before/after infection revealed that the virus-specific CD8+ T cells entered the DLN and activated in a sequential "conveyor belt"-like fashion. These results indicate that the tempo of CD8+ T cell activation/proliferation after viral infection is dependent on the tempo of RDC migration to the DLN and that T cell activation occurs in an ordered sequential fashion.

Actively learning human gaze shifting paths for semantics-aware photo cropping.

PubMed

Zhang, Luming; Gao, Yue; Ji, Rongrong; Xia, Yingjie; Dai, Qionghai; Li, Xuelong

2014-05-01

Photo cropping is a widely used tool in printing industry, photography, and cinematography. Conventional cropping models suffer from the following three challenges. First, the deemphasized role of semantic contents that are many times more important than low-level features in photo aesthetics. Second, the absence of a sequential ordering in the existing models. In contrast, humans look at semantically important regions sequentially when viewing a photo. Third, the difficulty of leveraging inputs from multiple users. Experience from multiple users is particularly critical in cropping as photo assessment is quite a subjective task. To address these challenges, this paper proposes semantics-aware photo cropping, which crops a photo by simulating the process of humans sequentially perceiving semantically important regions of a photo. We first project the local features (graphlets in this paper) onto the semantic space, which is constructed based on the category information of the training photos. An efficient learning algorithm is then derived to sequentially select semantically representative graphlets of a photo, and the selecting process can be interpreted by a path, which simulates humans actively perceiving semantics in a photo. Furthermore, we learn a prior distribution of such active graphlet paths from training photos that are marked as aesthetically pleasing by multiple users. The learned priors enforce the corresponding active graphlet path of a test photo to be maximally similar to those from the training photos. Experimental results show that: 1) the active graphlet path accurately predicts human gaze shifting, and thus is more indicative for photo aesthetics than conventional saliency maps and 2) the cropped photos produced by our approach outperform its competitors in both qualitative and quantitative comparisons.

Sequential self-assembly of DNA functionalized droplets

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

Zhang, Yin; McMullen, Angus; Pontani, Lea-Laetitia

Complex structures and devices, both natural and manmade, are often constructed sequentially. From crystallization to embryogenesis, a nucleus or seed is formed and built upon. Sequential assembly allows for initiation, signaling, and logical programming, which are necessary for making enclosed, hierarchical structures. Though biology relies on such schemes, they have not been available in materials science. We demonstrate programmed sequential self-assembly of DNA functionalized emulsions. The droplets are initially inert because the grafted DNA strands are pre-hybridized in pairs. Active strands on initiator droplets then displace one of the paired strands and thus release its complement, which in turn activatesmore » the next droplet in the sequence, akin to living polymerization. This strategy provides time and logic control during the self-assembly process, and offers a new perspective on the synthesis of materials.« less

Sequential self-assembly of DNA functionalized droplets

DOE PAGES

Zhang, Yin; McMullen, Angus; Pontani, Lea-Laetitia; ...

2017-06-16

Complex structures and devices, both natural and manmade, are often constructed sequentially. From crystallization to embryogenesis, a nucleus or seed is formed and built upon. Sequential assembly allows for initiation, signaling, and logical programming, which are necessary for making enclosed, hierarchical structures. Though biology relies on such schemes, they have not been available in materials science. We demonstrate programmed sequential self-assembly of DNA functionalized emulsions. The droplets are initially inert because the grafted DNA strands are pre-hybridized in pairs. Active strands on initiator droplets then displace one of the paired strands and thus release its complement, which in turn activatesmore » the next droplet in the sequence, akin to living polymerization. This strategy provides time and logic control during the self-assembly process, and offers a new perspective on the synthesis of materials.« less

Assessment of a Mobile Game ("MobileKids Monster Manor") to Promote Physical Activity Among Children.

PubMed

Garde, Ainara; Umedaly, Aryannah; Abulnaga, S Mazdak; Robertson, Leah; Junker, Anne; Chanoine, Jean Pierre; Ansermino, J Mark; Dumont, Guy A

2015-04-01

The majority of children in North America are not meeting current physical activity guidelines. The purpose of this study was to evaluate the impact of a mobile phone game ("MobileKids Monster Manor") as a tool to promote voluntary physical activity among children. The game integrates data from an accelerometer-based activity monitor (Tractivity(®); Kineteks Corp., Vancouver, BC, Canada) wirelessly connected to a phone and was developed with the involvement of a team of young advisors (KidsCan Initiative: Involving Youth as Ambassadors for Research). Fifty-four children 8-13 years old completed a week of baseline data collection by wearing an accelerometer but receiving no feedback about their activity levels. The 54 children were then sequentially assigned to two groups: One group played "MobileKids Monster Manor," and the other received daily activity feedback (steps and active minutes) via an online program. The physical activity (baseline and intervention weeks) was measured using the activity monitor and compared using two-way repeated-measures analysis of variance (intervention×time). Forty-seven children with a body mass index (BMI) z-score of 0.35±1.18 successfully completed the study. Significant (P=0.01) increases in physical activity were observed during the intervention week in both the game and feedback groups (1191 and 796 steps/day, respectively). In the game group, greater physical activity was demonstrated in children with higher BMI z-score, showing 964 steps/day more per BMI z-score unit (P=0.03; 95 percent confidence interval of 98 to 1829). Further investigation is required to confirm that our game design promotes physical activity.

40 CFR 63.522 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Hazardous Air Pollutants for Epoxy Resins Production and Non-Nylon Polyamides Production § 63.522... that are related to the production of BLR or WSR, including process vents, storage tanks, wastewater... process involving the bulk movement of material through sequential manufacturing steps. Mass, temperature...

Biogenesis of the bacterial cbb3 cytochrome c oxidase: Active subcomplexes support a sequential assembly model.

PubMed

Durand, Anne; Bourbon, Marie-Line; Steunou, Anne-Soisig; Khalfaoui-Hassani, Bahia; Legrand, Camille; Guitton, Audrey; Astier, Chantal; Ouchane, Soufian

2018-01-19

The cbb 3 oxidase has a high affinity for oxygen and is required for growth of bacteria, including pathogens, in oxygen-limited environments. However, the assembly of this oxidase is poorly understood. Most cbb 3 are composed of four subunits: the catalytic CcoN subunit, the two cytochrome c subunits (CcoO and CcoP) involved in electron transfer, and the small CcoQ subunit with an unclear function. Here, we address the role of these four subunits in cbb 3 biogenesis in the purple bacterium Rubrivivax gelatinosus Analyses of membrane proteins from different mutants revealed the presence of active CcoNQO and CcoNO subcomplexes and also showed that the CcoP subunit is not essential for their assembly. However, CcoP was required for the oxygen reduction activity in the absence of CcoQ. We also found that CcoQ is dispensable for forming an active CcoNOP subcomplex in membranes. CcoNOP exhibited oxygen reductase activity, indicating that the cofactors (hemes b and copper for CcoN and cytochromes c for CcoO and CcoP) were present within the subunits. Finally, we discovered the presence of a CcoNQ subcomplex and showed that CcoN is the required anchor for the assembly of the full CcoNQOP complex. On the basis of these findings, we propose a sequential assembly model in which the CcoQ subunit is required for the early maturation step: CcoQ first associates with CcoN before the CcoNQ-CcoO interaction. CcoP associates to CcoNQO subcomplex in the late maturation step, and once the CcoNQOP complex is fully formed, CcoQ is released for degradation by the FtsH protease. This model could be conserved in other bacteria, including the pathogenic bacteria lacking the assembly factor CcoH as in R. gelatinosus . © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

Increase of fruity aroma during mixed T. delbrueckii/S. cerevisiae wine fermentation is linked to specific esters enhancement.

PubMed

Renault, Philippe; Coulon, Joana; de Revel, Gilles; Barbe, Jean-Christophe; Bely, Marina

2015-08-17

The aim of this work was to study ester formation and the aromatic impact of Torulaspora delbrueckii when used in association with Saccharomyces cerevisiae during the alcoholic fermentation of must. In order to evaluate the influence of the inoculation procedure, sequential and simultaneous mixed cultures were carried out and compared to pure cultures of T. delbrueckii and S. cerevisiae. Our results showed that mixed inoculations allowed the increase, in comparison to S. cerevisiae pure culture, of some esters specifically produced by T. delbrueckii and significantly correlated to the maximal T. delbrueckii population reached in mixed cultures. Thus, ethyl propanoate, ethyl isobutanoate and ethyl dihydrocinnamate were considered as activity markers of T. delbrueckii. On the other hand, isobutyl acetate and isoamyl acetate concentrations were systematically increased during mixed inoculations although not correlated with the development of either species but were rather due to positive interactions between these species. Favoring T. delbrueckii development when performing sequential inoculation enhanced the concentration of esters linked to T. delbrueckii activity. On the contrary, simultaneous inoculation restricted the growth of T. delbrueckii, limiting the production of its activity markers, but involved a very important production of numerous esters due to more important positive interactions between species. These results suggest that the ester concentrations enhancement via interactions during mixed modalities was due to S. cerevisiae production in response to the presence of T. delbrueckii. Finally, sensory analyses showed that mixed inoculations between T. delbrueckii and S. cerevisiae allowed to enhance the complexity and fruity notes of wine in comparison to S. cerevisiae pure culture. Furthermore, the higher levels of ethyl propanoate, ethyl isobutanoate, ethyl dihydrocinnamate and isobutyl acetate in mixed wines were found responsible for the increase of fruitiness and complexity. Copyright © 2015 Elsevier B.V. All rights reserved.

Stimulus information stored in lasting active and hidden network states is destroyed by network bursts

PubMed Central

Dranias, Mark R.; Westover, M. Brandon; Cash, Sidney; VanDongen, Antonius M. J.

2015-01-01

In both humans and animals brief synchronizing bursts of epileptiform activity known as interictal epileptiform discharges (IEDs) can, even in the absence of overt seizures, cause transient cognitive impairments (TCI) that include problems with perception or short-term memory. While no evidence from single units is available, it has been assumed that IEDs destroy information represented in neuronal networks. Cultured neuronal networks are a model for generic cortical microcircuits, and their spontaneous activity is characterized by the presence of synchronized network bursts (SNBs), which share a number of properties with IEDs, including the high degree of synchronization and their spontaneous occurrence in the absence of an external stimulus. As a model approach to understanding the processes underlying IEDs, optogenetic stimulation and multielectrode array (MEA) recordings of cultured neuronal networks were used to study whether stimulus information represented in these networks survives SNBs. When such networks are optically stimulated they encode and maintain stimulus information for as long as one second. Experiments involved recording the network response to a single stimulus and trials where two different stimuli were presented sequentially, akin to a paired pulse trial. We broke the sequential stimulus trials into encoding, delay and readout phases and found that regardless of which phase the SNB occurs, stimulus-specific information was impaired. SNBs were observed to increase the mean network firing rate, but this did not translate monotonically into increases in network entropy. It was found that the more excitable a network, the more stereotyped its response was during a network burst. These measurements speak to whether SNBs are capable of transmitting information in addition to blocking it. These results are consistent with previous reports and provide baseline predictions concerning the neural mechanisms by which IEDs might cause TCI. PMID:25755638

Distal regulatory regions restrict the expression of cis-linked genes to the tapetal cells.

PubMed

Franco, Luciana O; de O Manes, Carmem Lara; Hamdi, Said; Sachetto-Martins, Gilberto; de Oliveira, Dulce E

2002-04-24

The oleosin glycine-rich protein genes Atgrp-6, Atgrp-7, and Atgrp-8 occur in clusters in the Arabidopsis genome and are expressed specifically in the tapetum cells. The cis-regulatory regions involved in the tissue-specific gene expression were investigated by fusing different segments of the gene cluster to the uidA reporter gene. Common distal regulatory regions were identified that coordinate expression of the sequential genes. At least two of these genes were regulated spatially by proximal and distal sequences. The cis-acting elements (122 bp upstream of the transcriptional start point) drive the uidA expression to floral tissues, whereas distal 5' upstream regions restrict the gene activity to tapetal cells.

Novel alkynyl substituted 3,4-dihydropyrimidin-2(1H)-one derivatives as potential inhibitors of chorismate mutase.

PubMed

Mallikarjuna Rao, V; Mahesh Kumar, P; Rambabu, D; Kapavarapu, Ravikumar; Shobha Rani, S; Misra, Parimal; Pal, Manojit

2013-12-01

A series of novel alkynyl substituted 3,4-dihydropyrimidin-2(1H)-one (DHPM) derivatives were designed, synthesized and evaluated in vitro as potential inhibitors of chorismate mutase (CM). All these compounds were prepared via a multi-component reaction (MCR) involving sequential I2-mediated Biginelli reaction followed by Cu-free Sonogashira coupling. Some of them showed promising inhibitory activities when tested at 30μM. One compound showed dose dependent inhibition of CM with IC50 value of 14.76±0.54μM indicating o-alkynylphenyl substituted DHPM as a new scaffold for the discovery of promising inhibitors of CM. Copyright © 2013 Elsevier Inc. All rights reserved.

Adaptive web sampling.

PubMed

Thompson, Steven K

2006-12-01

A flexible class of adaptive sampling designs is introduced for sampling in network and spatial settings. In the designs, selections are made sequentially with a mixture distribution based on an active set that changes as the sampling progresses, using network or spatial relationships as well as sample values. The new designs have certain advantages compared with previously existing adaptive and link-tracing designs, including control over sample sizes and of the proportion of effort allocated to adaptive selections. Efficient inference involves averaging over sample paths consistent with the minimal sufficient statistic. A Markov chain resampling method makes the inference computationally feasible. The designs are evaluated in network and spatial settings using two empirical populations: a hidden human population at high risk for HIV/AIDS and an unevenly distributed bird population.

First-principles multiple-barrier diffusion theory. The case study of interstitial diffusion in CdTe

DOE PAGES

Yang, Ji -Hui; Park, Ji -Sang; Kang, Joongoo; ...

2015-02-17

The diffusion of particles in solid-state materials generally involves several sequential thermal-activation processes. However, presently, diffusion coefficient theory only deals with a single barrier, i.e., it lacks an accurate description to deal with multiple-barrier diffusion. Here, we develop a general diffusion coefficient theory for multiple-barrier diffusion. Using our diffusion theory and first-principles calculated hopping rates for each barrier, we calculate the diffusion coefficients of Cd, Cu, Te, and Cl interstitials in CdTe for their full multiple-barrier diffusion pathways. As a result, we found that the calculated diffusivity agrees well with the experimental measurement, thus justifying our theory, which is generalmore » for many other systems.« less

Kinetic study of the processing by dipeptidyl-peptidase IV/CD26 of neuropeptides involved in pancreatic insulin secretion.

PubMed

Lambeir, A M; Durinx, C; Proost, P; Van Damme, J; Scharpé, S; De Meester, I

2001-11-02

Dipeptidyl-peptidase IV (DPPIV/CD26) metabolizes neuropeptides regulating insulin secretion. We studied the in vitro steady-state kinetics of DPPIV/CD26-mediated truncation of vasoactive intestinal peptide (VIP), pituitary adenylyl cyclase-activating peptide (PACAP27 and PACAP38), gastrin-releasing peptide (GRP) and neuropeptide Y (NPY). DPPIV/CD26 sequentially cleaves off two dipeptides of VIP, PACAP27, PACAP38 and GRP. GRP situates between the best DPPIV/CD26 substrates reported, comparable to NPY. Surprisingly, the C-terminal extension of PACAP38, distant from the scissile bond, improves both PACAP38 binding and turnover. Therefore, residues remote from the scissile bond can modulate DPPIV/CD26 substrate selectivity as well as residues flanking it.

Bursts and Heavy Tails in Temporal and Sequential Dynamics of Foraging Decisions

PubMed Central

Jung, Kanghoon; Jang, Hyeran; Kralik, Jerald D.; Jeong, Jaeseung

2014-01-01

A fundamental understanding of behavior requires predicting when and what an individual will choose. However, the actual temporal and sequential dynamics of successive choices made among multiple alternatives remain unclear. In the current study, we tested the hypothesis that there is a general bursting property in both the timing and sequential patterns of foraging decisions. We conducted a foraging experiment in which rats chose among four different foods over a continuous two-week time period. Regarding when choices were made, we found bursts of rapidly occurring actions, separated by time-varying inactive periods, partially based on a circadian rhythm. Regarding what was chosen, we found sequential dynamics in affective choices characterized by two key features: (a) a highly biased choice distribution; and (b) preferential attachment, in which the animals were more likely to choose what they had previously chosen. To capture the temporal dynamics, we propose a dual-state model consisting of active and inactive states. We also introduce a satiation-attainment process for bursty activity, and a non-homogeneous Poisson process for longer inactivity between bursts. For the sequential dynamics, we propose a dual-control model consisting of goal-directed and habit systems, based on outcome valuation and choice history, respectively. This study provides insights into how the bursty nature of behavior emerges from the interaction of different underlying systems, leading to heavy tails in the distribution of behavior over time and choices. PMID:25122498

Biomarker Sensors and Method for Multi-Color Imaging and Processing of Single-Molecule Life Signatures

NASA Technical Reports Server (NTRS)

Wade, Lawrence A. (Inventor); Collier, Charles Patrick (Inventor)

2013-01-01

The invention is a device including array of active regions for use in reacting one or more species in at least two of the active regions in a sequential process, e.g., sequential reactions. The device has a transparent substrate member, which has a surface region and a silane material overlying the surface region. A first active region overlies a first portion of the silane material. The first region has a first dimension of less than 1 micron in size and has first molecules capable of binding to the first portion of the silane material. A second active region overlies a second portion of the silane material. The second region has a second dimension of less than 1 micron in size, second molecules capable of binding to the second portion of the active region, and a spatial distance separates the first active region and the second active region.

Titanium(IV) isopropoxide mediated synthesis of pyrimidin-4-ones.

PubMed

Ramanjulu, Joshi M; Demartino, Michael P; Lan, Yunfeng; Marquis, Robert

2010-05-21

A novel, one-step method for the synthesis of tri- and tetrasubstituted pyrimidin-4-ones is reported. This method involves a titanium(IV)-mediated cyclization involving two sequential condensations of primary and beta-ketoamides. The reaction is operationally facile, readily scalable, and offers rapid entry into differentially substituted pyrimidin-4-one scaffolds. The high functional group compatibility allows for substantial diversification in the products generated from this transformation.

The architecture of visual narrative comprehension: the interaction of narrative structure and page layout in understanding comics.

PubMed

Cohn, Neil

2014-01-01

How do people make sense of the sequential images in visual narratives like comics? A growing literature of recent research has suggested that this comprehension involves the interaction of multiple systems: The creation of meaning across sequential images relies on a "narrative grammar" that packages conceptual information into categorical roles organized in hierarchic constituents. These images are encapsulated into panels arranged in the layout of a physical page. Finally, how panels frame information can impact both the narrative structure and page layout. Altogether, these systems operate in parallel to construct the Gestalt whole of comprehension of this visual language found in comics.

A controlled experiment on the impact of software structure on maintainability

NASA Technical Reports Server (NTRS)

Rombach, Dieter H.

1987-01-01

The impact of software structure on maintainability aspects including comprehensibility, locality, modifiability, and reusability in a distributed system environment is studied in a controlled maintenance experiment involving six medium-size distributed software systems implemented in LADY (language for distributed systems) and six in an extended version of sequential PASCAL. For all maintenance aspects except reusability, the results were quantitatively given in terms of complexity metrics which could be automated. The results showed LADY to be better suited to the development of maintainable software than the extension of sequential PASCAL. The strong typing combined with high parametrization of units is suggested to improve the reusability of units in LADY.

Short-term memory for spatial, sequential and duration information.

PubMed

Manohar, Sanjay G; Pertzov, Yoni; Husain, Masud

2017-10-01

Space and time appear to play key roles in the way that information is organized in short-term memory (STM). Some argue that they are crucial contexts within which other stored features are embedded, allowing binding of information that belongs together within STM. Here we review recent behavioral, neurophysiological and imaging studies that have sought to investigate the nature of spatial, sequential and duration representations in STM, and how these might break down in disease. Findings from these studies point to an important role of the hippocampus and other medial temporal lobe structures in aspects of STM, challenging conventional accounts of involvement of these regions in only long-term memory.

A Sequential Optimization Sampling Method for Metamodels with Radial Basis Functions

PubMed Central

Pan, Guang; Ye, Pengcheng; Yang, Zhidong

2014-01-01

Metamodels have been widely used in engineering design to facilitate analysis and optimization of complex systems that involve computationally expensive simulation programs. The accuracy of metamodels is strongly affected by the sampling methods. In this paper, a new sequential optimization sampling method is proposed. Based on the new sampling method, metamodels can be constructed repeatedly through the addition of sampling points, namely, extrema points of metamodels and minimum points of density function. Afterwards, the more accurate metamodels would be constructed by the procedure above. The validity and effectiveness of proposed sampling method are examined by studying typical numerical examples. PMID:25133206

Sequential capture of CO2 and SO2 in a pressurized TGA simulating FBC conditions.

PubMed

Sun, Ping; Grace, John R; Lim, C Jim; Anthony, Edward J

2007-04-15

Four FBC-based processes were investigated as possible means of sequentially capturing SO2 and CO2. Sorbent performance is the key to their technical feasibility. Two sorbents (a limestone and a dolomite) were tested in a pressurized thermogravimetric analyzer (PTGA). The sorbent behaviors were explained based on complex interaction between carbonation, sulfation, and direct sulfation. The best option involved using limestone or dolomite as a SO2-sorbent in a FBC combustor following cyclic CO2 capture. Highly sintered limestone is a good sorbent for SO2 because of the generation of macropores during calcination/carbonation cycling.

α2 Integrin, extracellular matrix metalloproteinase inducer, and matrix metalloproteinase-3 act sequentially to induce differentiation of mouse embryonic stem cells into odontoblast-like cells

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

Ozeki, Nobuaki; Kawai, Rie; Hase, Naoko

We previously reported that interleukin 1β acts via matrix metalloproteinase (MMP)-3 to regulate cell proliferation and suppress apoptosis in α2 integrin-positive odontoblast-like cells differentiated from mouse embryonic stem (ES) cells. Here we characterize the signal cascade underpinning odontoblastic differentiation in mouse ES cells. The expression of α2 integrin, extracellular matrix metalloproteinase inducer (Emmprin), and MMP-3 mRNA and protein were all potently increased during odontoblastic differentiation. Small interfering RNA (siRNA) disruption of the expression of these effectors potently suppressed the expression of the odontoblastic biomarkers dentin sialophosphoprotein, dentin matrix protein-1 and alkaline phosphatase, and blocked odontoblast calcification. Our siRNA, western blotmore » and blocking antibody analyses revealed a unique sequential cascade involving α2 integrin, Emmprin and MMP-3 that drives ES cell differentiation into odontoblasts. This cascade requires the interaction between α2 integrin and Emmprin and is potentiated by exogenous MMP-3. Finally, although odontoblast-like cells potently express α2, α6, αV, β1, and β3, integrins, we confirmed that β1 integrin acts as the trigger for ES cell differentiation, apparently in complex with α2 integrin. These results demonstrate a unique and unanticipated role for an α2 integrin-, Emmprin-, and MMP-3-mediated signaling cascade in driving mouse ES cell differentiation into odontoblast-like cells. - Highlights: • Odontoblast differentiation requires activation of α2 integrin, Emmprin and MMP-3. • α2 integrin, Emmprin and MMP-3 form a sequential signaling cascade. • β1 integrin acts a specific trigger for odontoblast differentiation. • The role of these effectors is highly novel and unanticipated.« less

Dnmts and Tet target memory-associated genes after appetitive olfactory training in honey bees

PubMed Central

Biergans, Stephanie D.; Giovanni Galizia, C.; Reinhard, Judith; Claudianos, Charles

2015-01-01

DNA methylation and demethylation are epigenetic mechanisms involved in memory formation. In honey bees DNA methyltransferase (Dnmt) function is necessary for long-term memory to be stimulus specific (i.e. to reduce generalization). So far, however, it remains elusive which genes are targeted and what the time-course of DNA methylation is during memory formation. Here, we analyse how DNA methylation affects memory retention, gene expression, and differential methylation in stimulus-specific olfactory long-term memory formation. Out of 30 memory-associated genes investigated here, 9 were upregulated following Dnmt inhibition in trained bees. These included Dnmt3 suggesting a negative feedback loop for DNA methylation. Within these genes also the DNA methylation pattern changed during the first 24 hours after training. Interestingly, this was accompanied by sequential activation of the DNA methylation machinery (i.e. Dnmts and Tet). In sum, memory formation involves a temporally complex epigenetic regulation of memory-associated genes that facilitates stimulus specific long-term memory in the honey bee. PMID:26531238

The central role of recognition in auditory perception: a neurobiological model.

PubMed

McLachlan, Neil; Wilson, Sarah

2010-01-01

The model presents neurobiologically plausible accounts of sound recognition (including absolute pitch), neural plasticity involved in pitch, loudness and location information integration, and streaming and auditory recall. It is proposed that a cortical mechanism for sound identification modulates the spectrotemporal response fields of inferior colliculus neurons and regulates the encoding of the echoic trace in the thalamus. Identification involves correlation of sequential spectral slices of the stimulus-driven neural activity with stored representations in association with multimodal memories, verbal lexicons, and contextual information. Identities are then consolidated in auditory short-term memory and bound with attribute information (usually pitch, loudness, and direction) that has been integrated according to the identities' spectral properties. Attention to, or recall of, a particular identity will excite a particular sequence in the identification hierarchies and so lead to modulation of thalamus and inferior colliculus neural spectrotemporal response fields. This operates as an adaptive filter for identities, or their attributes, and explains many puzzling human auditory behaviors, such as the cocktail party effect, selective attention, and continuity illusions.

Alpha-band rhythm suppression during memory recall reflecting memory performance.

PubMed

Yokosawa, Koichi; Kimura, Keisuke; Chitose, Ryota; Momiki, Takuya; Kuriki, Shinya

2016-08-01

Alpha-band rhythm is thought to be involved in memory processes, similarly to other spontaneous brain rhythms. Ten right-handed healthy volunteers participated in our proposed sequential short-term memory task that provides a serial position effect in accuracy rate. We recorded alpha-band rhythms by magnetoencephalography during performance of the task and observed that the amplitude of the rhythm was suppressed dramatically in the memory recall period. The suppressed region was estimated to be in the occipital lobe, suggesting that alpha-band rhythm is suppressed by activation of the occipital attentional network. Additionally, the alpha-band suppression reflected accuracy rate, that is, the amplitude was suppressed more when recalling items with higher accuracy rate. The sensors with a significant correlation between alpha-band amplitude and accuracy rate were located widely from the frontal to occipital regions mainly in the right hemisphere. The results suggests that alpha-band rhythm is involved in memory recall and can be index of memory performance.

Gamma activity modulated by naming of ambiguous and unambiguous images: intracranial recording

PubMed Central

Cho-Hisamoto, Yoshimi; Kojima, Katsuaki; Brown, Erik C; Matsuzaki, Naoyuki; Asano, Eishi

2014-01-01

OBJECTIVE Humans sometimes need to recognize objects based on vague and ambiguous silhouettes. Recognition of such images may require an intuitive guess. We determined the spatial-temporal characteristics of intracranially-recorded gamma activity (at 50–120 Hz) augmented differentially by naming of ambiguous and unambiguous images. METHODS We studied ten patients who underwent epilepsy surgery. Ambiguous and unambiguous images were presented during extraoperative electrocorticography recording, and patients were instructed to overtly name the object as it is first perceived. RESULTS Both naming tasks were commonly associated with gamma-augmentation sequentially involving the occipital and occipital-temporal regions, bilaterally, within 200 ms after the onset of image presentation. Naming of ambiguous images elicited gamma-augmentation specifically involving portions of the inferior-frontal, orbitofrontal, and inferior-parietal regions at 400 ms and after. Unambiguous images were associated with more intense gamma-augmentation in portions of the occipital and occipital-temporal regions. CONCLUSIONS Frontal-parietal gamma-augmentation specific to ambiguous images may reflect the additional cortical processing involved in exerting intuitive guess. Occipital gamma-augmentation enhanced during naming of unambiguous images can be explained by visual processing of stimuli with richer detail. SIGNIFICANCE Our results support the theoretical model that guessing processes in visual domain occur following the accumulation of sensory evidence resulting from the bottom-up processing in the occipital-temporal visual pathways. PMID:24815577

Sequential Transition Patterns of Preschoolers' Social Interactions during Child-Initiated Play: Is Parallel-Aware Play a Bidirectional Bridge to Other Play States?

ERIC Educational Resources Information Center

Robinson, Clyde C.; Anderson, Genan T.; Porter, Christin L.; Hart, Craig, H.; Wouden-Miller, Melissa

2003-01-01

Explored the simultaneous sequential transition patterns of preschoolers' social play within classroom settings. Found that the proportion of social-play states did not vary during play episodes even when accounting for type of activity center, gender, and SES. Found a reciprocal relationship between parallel-aware and other social-play states…

Neuroimaging reveals dual routes to reading in simultaneous proficient readers of two orthographies

PubMed Central

Das, T.; Padakannaya, P.; Pugh, K. R.; Singh, N. C.

2012-01-01

Orthographic differences across languages impose differential weighting on distinct component processes, and consequently on different pathways during word-reading tasks. Readers of transparent orthographies such as Italian and Hindi are thought to rely on spelling-to-sound assembly and show increased activation in phonologically-tuned areas along the dorsal pathway, whereas reading an opaque orthography such as English is thought to rely more on lexically-mediated processing associated with increased activation of semantically-tuned regions along the ventral pathway. To test if biliterate Hindi/English readers exhibit orthography-specific reading pathways, we used behavioural measures and functional neuroimaging. Reaction times and activation patterns of monolingual English and Hindi readers were compared to two groups of adult biliterates; 14 simultaneous readers who learnt to read both languages at age 5 and 10 sequential readers who learnt Hindi at 5 and English at 10. Simultaneous, but not sequential readers demonstrated relative activation differences of dorsal and ventral areas in the two languages. Similar to native counterparts, simultaneous readers preferentially activated the left inferior temporal gyrus for English and left inferior parietal lobule (L-IPL) for Hindi, whereas, sequential readers showed higher activation along the L-IPL for reading both languages. We suggest that early simultaneous exposure to reading distinct orthographies results in orthography-specific plasticity that persists through adulthood. PMID:20854914

Secretome analysis of Trichoderma reesei and Aspergillus niger cultivated by submerged and sequential fermentation processes: Enzyme production for sugarcane bagasse hydrolysis.

PubMed

Florencio, Camila; Cunha, Fernanda M; Badino, Alberto C; Farinas, Cristiane S; Ximenes, Eduardo; Ladisch, Michael R

2016-08-01

Cellulases and hemicellulases from Trichoderma reesei and Aspergillus niger have been shown to be powerful enzymes for biomass conversion to sugars, but the production costs are still relatively high for commercial application. The choice of an effective microbial cultivation process employed for enzyme production is important, since it may affect titers and the profile of protein secretion. We used proteomic analysis to characterize the secretome of T. reesei and A. niger cultivated in submerged and sequential fermentation processes. The information gained was key to understand differences in hydrolysis of steam exploded sugarcane bagasse for enzyme cocktails obtained from two different cultivation processes. The sequential process for cultivating A. niger gave xylanase and β-glucosidase activities 3- and 8-fold higher, respectively, than corresponding activities from the submerged process. A greater protein diversity of critical cellulolytic and hemicellulolytic enzymes were also observed through secretome analyses. These results helped to explain the 3-fold higher yield for hydrolysis of non-washed pretreated bagasse when combined T. reesei and A. niger enzyme extracts from sequential fermentation were used in place of enzymes obtained from submerged fermentation. An enzyme loading of 0.7 FPU cellulase activity/g glucan was surprisingly effective when compared to the 5-15 times more enzyme loadings commonly reported for other cellulose hydrolysis studies. Analyses showed that more than 80% consisted of proteins other than cellulases whose role is important to the hydrolysis of a lignocellulose substrate. Our work combined proteomic analyses and enzymology studies to show that sequential and submerged cultivation methods differently influence both titers and secretion profile of key enzymes required for the hydrolysis of sugarcane bagasse. The higher diversity of feruloyl esterases, xylanases and other auxiliary hemicellulolytic enzymes observed in the enzyme mixtures from the sequential fermentation could be one major reason for the more efficient enzyme hydrolysis that results when using the combined secretomes from A. niger and T. reesei. Copyright © 2016 Elsevier Inc. All rights reserved.

Aging and List-Wide Modulations of Strategy Execution:A Study in Arithmetic.

PubMed

Hinault, Thomas; Lemaire, Patrick

2017-01-01

Background/Study Context: This study aimed at further our understanding of the cognitive processes involved during strategy execution, and how the processes involved change with age. More specifically, the main goal was to investigate whether poorer-strategy effects (i.e., poorer performance when a cued strategy is not the best) and sequential modulations of poorer-strategy effects (i.e., decreased poorer-strategy effects on current problems following poorer-strategy problems compared with after better-strategy problems) are influenced by proportions of poorer-strategy problems. We used a computational estimation task (i.e., providing approximate products to two-digit multiplication problems such as 38 × 74) with problems sets including 75%, 50%, or 25% of poorer-strategy problems (i.e., participants have to estimate products with another strategy than the better strategy). The remaining problems were cued with the better strategy. Age-related differences were also investigated. We found that proportions of poorer-strategy problems influenced sequential modulations of poorer-strategy effects. Indeed, sequential modulations of poorer-strategy effects were larger when proportions of poorer-strategy problems were equal than unequal. Moreover, proportion effects were different for young and older adults, as older adults benefited more from low proportions of poorer-strategy problems compared with young adults. These findings have important implications regarding cognitive control mechanisms underlying both list-wide and trial-to-trial modulations of strategy execution, and how these processes change during aging.

Bending Genders: The Biology of Natural Sex Change in Fish.

PubMed

Todd, Erica V; Liu, Hui; Muncaster, Simon; Gemmell, Neil J

2016-01-01

Sexual fate is no longer seen as an irreversible deterministic switch set during early embryonic development but as an ongoing battle for primacy between male and female developmental trajectories. That sexual fate is not final and must be actively maintained via continuous suppression of the opposing sexual network creates the potential for flexibility into adulthood. In many fishes, sexuality is not only extremely plastic, but sex change is a usual and adaptive part of the life cycle. Sequential hermaphrodites begin life as one sex, changing sometime later to the other, and include species capable of protandrous (male-to-female), protogynous (female-to-male), or serial (bidirectional) sex change. Natural sex change involves coordinated transformations across multiple biological systems, including behavioural, anatomical, neuroendocrine, and molecular axes. We here review the biological processes underlying this amazing transformation, focussing particularly on its molecular basis, which remains poorly understood, but where new genomic technologies are significantly advancing our understanding of how sex change is initiated and progressed at the molecular level. Knowledge of how a usually committed developmental process remains plastic in sequentially hermaphroditic fishes is relevant to understanding the evolution and functioning of sexual developmental systems in vertebrates generally, as well as pathologies of sexual development in humans. © 2016 S. Karger AG, Basel.

The effect of random or sequential presentation of targets during robot-assisted therapy on children.

PubMed

Ladenheim, Barbara; Altenburger, Peter; Cardinal, Ryan; Monterroso, Linda; Dierks, Tracy; Mast, Joelle; Krebs, Hermano Igo

2013-01-01

Robot assisted upper extremity therapy has been shown to be effective in adult stroke patients and in children with cerebral palsy (CP) and other acquired brain injuries (ABI). The patient's active involvement is a factor in its efficacy. However, this demands focused attention during training sessions, which can be a challenge for children. To compare results of training requiring two different levels of focused attention. Differences in short term performance and retention of gains as a function of training protocol as measured by the Fugl-Meyer (FM) were predicted. Thirty-one children with CP or ABI were randomly divided into two groups. All received 16 one hour sessions of robot-assisted therapy (twice a week for 8 weeks) where they moved a robot handle to direct a cursor on the screen toward designated targets. One group had targets presented sequentially in clockwise fashion, the other presented in random order. Thus, one group could anticipate the position of each target, the other could not. Both groups showed significant functional improvement after therapy, but no significant difference between groups was observed. Assist-as-needed robotic training is effective in children with CP or ABI with small non-significant differences attributed to attentional demand.

Biochemical Characterization of 3-Methyl-4-nitrophenol Degradation in Burkholderia sp. Strain SJ98

PubMed Central

Min, Jun; Lu, Yang; Hu, Xiaoke; Zhou, Ning-Yi

2016-01-01

Several strains have been reported to grow on 3-methyl-4-nitrophenol (3M4NP), the primary breakdown product of the excessively used insecticide fenitrothion. However, the microbial degradation of 3M4NP at molecular and biochemical levels remains unknown. Here, methyl-1,4-benzoquinone (MBQ) and methylhydroquinone (MHQ), rather than catechol proposed previously, were identified as the intermediates before ring cleavage during 3M4NP degradation by Burkholderia sp. strain SJ98. Real-time quantitative PCR analysis indicated that the pnpABA1CDEF cluster involved in para-nitrophenol (PNP) and 2-chloro-4-nitrophenol (2C4NP) catabolism was also likely responsible for 3M4NP degradation in this strain. Purified PNP 4-monooxygenase (PnpA) is able to catalyze the monooxygenation of 3M4NP to MBQ and exhibited an apparent Km value of 20.3 ± 2.54 μM for 3M4NP, and pnpA is absolutely necessary for the catabolism of 3M4NP by gene knock-out and complementation. PnpB, a 1,4-benzoquinone reductase catalyzes the reduction of MBQ to MHQ, and also found to enhance PnpA activity in vitro in the conversion of 3M4NP to MBQ. By sequential catalysis assays, PnpCD, PnpE, and PnpF were likely involved in the lower pathway of 3M4NP catabolism. Although NpcCD, NpcE, and NpcF are able to catalyze the sequential conversion of MHQ in vitro, these enzymes are unlikely involved in 3M4NP catabolism because their coding genes were not upregulated by 3M4NP induction in vivo. These results revealed that the enzymes involved in PNP and 2C4NP catabolism were also responsible for 3M4NP degradation in strain SJ98. This fills a gap in our understanding of the microbial degradation of 3M4NP at molecular and biochemical levels and also provides another example to illustrate the adaptive flexibility in microbial catabolism for structurally similar compounds. PMID:27252697

Heuristic and optimal policy computations in the human brain during sequential decision-making.

PubMed

Korn, Christoph W; Bach, Dominik R

2018-01-23

Optimal decisions across extended time horizons require value calculations over multiple probabilistic future states. Humans may circumvent such complex computations by resorting to easy-to-compute heuristics that approximate optimal solutions. To probe the potential interplay between heuristic and optimal computations, we develop a novel sequential decision-making task, framed as virtual foraging in which participants have to avoid virtual starvation. Rewards depend only on final outcomes over five-trial blocks, necessitating planning over five sequential decisions and probabilistic outcomes. Here, we report model comparisons demonstrating that participants primarily rely on the best available heuristic but also use the normatively optimal policy. FMRI signals in medial prefrontal cortex (MPFC) relate to heuristic and optimal policies and associated choice uncertainties. Crucially, reaction times and dorsal MPFC activity scale with discrepancies between heuristic and optimal policies. Thus, sequential decision-making in humans may emerge from integration between heuristic and optimal policies, implemented by controllers in MPFC.

Biodegradation and detoxification of textile azo dyes by bacterial consortium under sequential microaerophilic/aerobic processes

PubMed Central

Lade, Harshad; Kadam, Avinash; Paul, Diby; Govindwar, Sanjay

2015-01-01

Release of textile azo dyes to the environment is an issue of health concern while the use of microorganisms has proved to be the best option for remediation. Thus, in the present study, a bacterial consortium consisting of Providencia rettgeri strain HSL1 and Pseudomonas sp. SUK1 has been investigated for degradation and detoxification of structurally different azo dyes. The consortium showed 98-99 % decolorization of all the selected azo dyes viz. Reactive Black 5 (RB 5), Reactive Orange 16 (RO 16), Disperse Red 78 (DR 78) and Direct Red 81 (DR 81) within 12 to 30 h at 100 mg L-1 concentration at 30 ± 0.2 °C under microaerophilic, sequential aerobic/microaerophilic and microaerophilic/aerobic processes. However, decolorization under microaerophilic conditions viz. RB 5 (0.26 mM), RO 16 (0.18 mM), DR 78 (0.20 mM) and DR 81 (0.23 mM) and sequential aerobic/microaerophilic processes viz. RB 5 (0.08 mM), RO 16 (0.06 mM), DR 78 (0.07 mM) and DR 81 (0.09 mM) resulted into the formation of aromatic amines. In distinction, sequential microaerophilic/ aerobic process doesn’t show the formation of amines. Additionally, 62-72 % reduction in total organic carbon content was observed in all the dyes decolorized broths under sequential microaerophilic/aerobic processes suggesting the efficacy of method in mineralization of dyes. Notable induction within the levels of azoreductase and NADH-DCIP reductase (97 and 229 % for RB 5, 55 and 160 % for RO 16, 63 and 196 % for DR 78, 108 and 258 % for DR 81) observed under sequential microaerophilic/aerobic processes suggested their critical involvements in the initial breakdown of azo bonds, whereas, a slight increase in the levels of laccase and veratryl alcohol oxidase confirmed subsequent oxidation of formed amines. Also, the acute toxicity assay with Daphnia magna revealed the nontoxic nature of the dye-degraded metabolites under sequential microaerophilic/aerobic processes. As biodegradation under sequential microaerophilic/aerobic process completely detoxified all the selected textile azo dyes, further efforts should be made to implement such methods for large scale dye wastewater treatment technologies. PMID:26417357

Brain networks of temporal preparation: A multiple regression analysis of neuropsychological data.

PubMed

Triviño, Mónica; Correa, Ángel; Lupiáñez, Juan; Funes, María Jesús; Catena, Andrés; He, Xun; Humphreys, Glyn W

2016-11-15

There are only a few studies on the brain networks involved in the ability to prepare in time, and most of them followed a correlational rather than a neuropsychological approach. The present neuropsychological study performed multiple regression analysis to address the relationship between both grey and white matter (measured by magnetic resonance imaging in patients with brain lesion) and different effects in temporal preparation (Temporal orienting, Foreperiod and Sequential effects). Two versions of a temporal preparation task were administered to a group of 23 patients with acquired brain injury. In one task, the cue presented (a red versus green square) to inform participants about the time of appearance (early versus late) of a target stimulus was blocked, while in the other task the cue was manipulated on a trial-by-trial basis. The duration of the cue-target time intervals (400 versus 1400ms) was always manipulated within blocks in both tasks. Regression analysis were conducted between either the grey matter lesion size or the white matter tracts disconnection and the three temporal preparation effects separately. The main finding was that each temporal preparation effect was predicted by a different network of structures, depending on cue expectancy. Specifically, the Temporal orienting effect was related to both prefrontal and temporal brain areas. The Foreperiod effect was related to right and left prefrontal structures. Sequential effects were predicted by both parietal cortex and left subcortical structures. These findings show a clear dissociation of brain circuits involved in the different ways to prepare in time, showing for the first time the involvement of temporal areas in the Temporal orienting effect, as well as the parietal cortex in the Sequential effects. Copyright © 2016 Elsevier Inc. All rights reserved.

Encoding Time in Feedforward Trajectories of a Recurrent Neural Network Model.

PubMed

Hardy, N F; Buonomano, Dean V

2018-02-01

Brain activity evolves through time, creating trajectories of activity that underlie sensorimotor processing, behavior, and learning and memory. Therefore, understanding the temporal nature of neural dynamics is essential to understanding brain function and behavior. In vivo studies have demonstrated that sequential transient activation of neurons can encode time. However, it remains unclear whether these patterns emerge from feedforward network architectures or from recurrent networks and, furthermore, what role network structure plays in timing. We address these issues using a recurrent neural network (RNN) model with distinct populations of excitatory and inhibitory units. Consistent with experimental data, a single RNN could autonomously produce multiple functionally feedforward trajectories, thus potentially encoding multiple timed motor patterns lasting up to several seconds. Importantly, the model accounted for Weber's law, a hallmark of timing behavior. Analysis of network connectivity revealed that efficiency-a measure of network interconnectedness-decreased as the number of stored trajectories increased. Additionally, the balance of excitation (E) and inhibition (I) shifted toward excitation during each unit's activation time, generating the prediction that observed sequential activity relies on dynamic control of the E/I balance. Our results establish for the first time that the same RNN can generate multiple functionally feedforward patterns of activity as a result of dynamic shifts in the E/I balance imposed by the connectome of the RNN. We conclude that recurrent network architectures account for sequential neural activity, as well as for a fundamental signature of timing behavior: Weber's law.

Inhibition during response preparation is sensitive to response complexity

PubMed Central

Saks, Dylan; Hoang, Timothy; Ivry, Richard B.

2015-01-01

Motor system excitability is transiently suppressed during the preparation of movement. This preparatory inhibition is hypothesized to facilitate response selection and initiation. Given that demands on selection and initiation processes increase with movement complexity, we hypothesized that complexity would influence preparatory inhibition. To test this hypothesis, we probed corticospinal excitability during a delayed-response task in which participants were cued to prepare right- or left-hand movements of varying complexity. Single-pulse transcranial magnetic stimulation was applied over right primary motor cortex to elicit motor evoked potentials (MEPs) from the first dorsal interosseous (FDI) of the left hand. MEP suppression was greater during the preparation of responses involving coordination of the FDI and adductor digiti minimi relative to easier responses involving only the FDI, independent of which hand was cued to respond. In contrast, this increased inhibition was absent when the complex responses required sequential movements of the two muscles. Moreover, complexity did not influence the level of inhibition when the response hand was fixed for the trial block, regardless of whether the complex responses were performed simultaneously or sequentially. These results suggest that preparatory inhibition contributes to response selection, possibly by suppressing extraneous movements when responses involve the simultaneous coordination of multiple effectors. PMID:25717168

Sequential bearings-only-tracking initiation with particle filtering method.

PubMed

Liu, Bin; Hao, Chengpeng

2013-01-01

The tracking initiation problem is examined in the context of autonomous bearings-only-tracking (BOT) of a single appearing/disappearing target in the presence of clutter measurements. In general, this problem suffers from a combinatorial explosion in the number of potential tracks resulted from the uncertainty in the linkage between the target and the measurement (a.k.a the data association problem). In addition, the nonlinear measurements lead to a non-Gaussian posterior probability density function (pdf) in the optimal Bayesian sequential estimation framework. The consequence of this nonlinear/non-Gaussian context is the absence of a closed-form solution. This paper models the linkage uncertainty and the nonlinear/non-Gaussian estimation problem jointly with solid Bayesian formalism. A particle filtering (PF) algorithm is derived for estimating the model's parameters in a sequential manner. Numerical results show that the proposed solution provides a significant benefit over the most commonly used methods, IPDA and IMMPDA. The posterior Cramér-Rao bounds are also involved for performance evaluation.

A class of temporal boundaries derived by quantifying the sense of separation.

PubMed

Paine, Llewyn Elise; Gilden, David L

2013-12-01

The perception of moment-to-moment environmental flux as being composed of meaningful events requires that memory processes coordinate with cues that signify beginnings and endings. We have constructed a technique that allows this coordination to be monitored indirectly. This technique works by embedding a sequential priming task into the event under study. Memory and perception must be coordinated to resolve temporal flux into scenes. The implicit memory processes inherent in sequential priming are able to effectively shadow then mirror scene-forming processes. Certain temporal boundaries are found to weaken the strength of irrelevant feature priming, a signal which can then be used in more ambiguous cases to infer how people segment time. Over the course of 13 independent studies, we were able to calibrate the technique and then use it to measure the strength of event segmentation in several instructive contexts that involved both visual and auditory modalities. The signal generated by sequential priming may permit the sense of separation between events to be measured as an extensive psychophysical quantity.

United Kingdom national paediatric bilateral cochlear implant audit: preliminary results.

PubMed

Cullington, Helen; Bele, Devyanee; Brinton, Julie; Lutman, Mark

2013-11-01

Prior to 2009, United Kingdom (UK) public funding was mainly only available for children to receive unilateral cochlear implants. In 2009, the National Institute for Health and Care Excellence published guidance for cochlear implantation following their review. According to these guidelines, all suitable children are eligible to have simultaneous bilateral cochlear implants or a sequential bilateral cochlear implant if they had received the first before the guidelines were published. Fifteen UK cochlear implant centres formed a consortium to carry out a multi-centre audit. The audit involves collecting data from simultaneously and sequentially implanted children at four intervals: before bilateral cochlear implants or before the sequential implant, 1, 2, and 3 years after bilateral implants. The measures include localization, speech recognition in quiet and background noise, speech production, listening, vocabulary, parental perception, quality of life, and surgical data including complications. The audit has now passed the 2-year point, and data have been received on 850 children. This article provides a first view of some data received up until March 2012.

Type I error probability spending for post-market drug and vaccine safety surveillance with binomial data.

PubMed

Silva, Ivair R

2018-01-15

Type I error probability spending functions are commonly used for designing sequential analysis of binomial data in clinical trials, but it is also quickly emerging for near-continuous sequential analysis of post-market drug and vaccine safety surveillance. It is well known that, for clinical trials, when the null hypothesis is not rejected, it is still important to minimize the sample size. Unlike in post-market drug and vaccine safety surveillance, that is not important. In post-market safety surveillance, specially when the surveillance involves identification of potential signals, the meaningful statistical performance measure to be minimized is the expected sample size when the null hypothesis is rejected. The present paper shows that, instead of the convex Type I error spending shape conventionally used in clinical trials, a concave shape is more indicated for post-market drug and vaccine safety surveillance. This is shown for both, continuous and group sequential analysis. Copyright © 2017 John Wiley & Sons, Ltd.

Microwave Ablation: Comparison of Simultaneous and Sequential Activation of Multiple Antennas in Liver Model Systems.

PubMed

Harari, Colin M; Magagna, Michelle; Bedoya, Mariajose; Lee, Fred T; Lubner, Meghan G; Hinshaw, J Louis; Ziemlewicz, Timothy; Brace, Christopher L

2016-01-01

To compare microwave ablation zones created by using sequential or simultaneous power delivery in ex vivo and in vivo liver tissue. All procedures were approved by the institutional animal care and use committee. Microwave ablations were performed in both ex vivo and in vivo liver models with a 2.45-GHz system capable of powering up to three antennas simultaneously. Two- and three-antenna arrays were evaluated in each model. Sequential and simultaneous ablations were created by delivering power (50 W ex vivo, 65 W in vivo) for 5 minutes per antenna (10 and 15 minutes total ablation time for sequential ablations, 5 minutes for simultaneous ablations). Thirty-two ablations were performed in ex vivo bovine livers (eight per group) and 28 in the livers of eight swine in vivo (seven per group). Ablation zone size and circularity metrics were determined from ablations excised postmortem. Mixed effects modeling was used to evaluate the influence of power delivery, number of antennas, and tissue type. On average, ablations created by using the simultaneous power delivery technique were larger than those with the sequential technique (P < .05). Simultaneous ablations were also more circular than sequential ablations (P = .0001). Larger and more circular ablations were achieved with three antennas compared with two antennas (P < .05). Ablations were generally smaller in vivo compared with ex vivo. The use of multiple antennas and simultaneous power delivery creates larger, more confluent ablations with greater temperatures than those created with sequential power delivery. © RSNA, 2015.

Statistical Discourse Analysis: A Method for Modelling Online Discussion Processes

ERIC Educational Resources Information Center

Chiu, Ming Ming; Fujita, Nobuko

2014-01-01

Online forums (synchronous and asynchronous) offer exciting data opportunities to analyze how people influence one another through their interactions. However, researchers must address several analytic difficulties involving the data (missing values, nested structure [messages within topics], non-sequential messages), outcome variables (discrete…

Do (un)certainty appraisal tendencies reverse the influence of emotions on risk taking in sequential tasks?

PubMed

Bagneux, Virginie; Bollon, Thierry; Dantzer, Cécile

2012-01-01

According to the Appraisal-Tendency Framework (Han, Lerner, & Keltner, 2007), certainty-associated emotions increase risk taking compared with uncertainty-associated emotions. To date, this general effect has only been shown in static judgement and decision-making paradigms; therefore, the present study tested the effect of certainty on risk taking in a sequential decision-making task. We hypothesised that the effect would be reversed due to the kind of processing involved, as certainty is considered to encourage heuristic processing that takes into account the emotional cues arising from previous decisions, whereas uncertainty leads to more systematic processing. One hundred and one female participants were induced to feel one of three emotions (film clips) before performing a decision-making task involving risk (Game of Dice Task; Brand et al., 2005). As expected, the angry and happy participants (certainty-associated emotions) were more likely than the fearful participants (uncertainty-associated emotion) to make safe decisions (vs. risky decisions).

[Clinical study on the treatment of acute paraquat poisoning with sequential whole gastric and bowel irrigation].

PubMed

Zhao, Bo; Dai, Jingbin; Li, Jun; Xiao, Lei; Sun, Baoquan; Liu, Naizheng; Zhang, Yanmin; Jian, Xiangdong

2015-03-01

To explore the clinical efficacy of early application of sequential gastrointestinal lavage in patients with acute paraquat poisoning by analyzing the clinical data of 97 patients. A total of 97 eligible patients with acute paraquat poisoning were divided into conventional treatment group (n = 48) and sequential treatment group (n = 49). The conventional treatment group received routine gastric lavage with water. Then 30 g of montmorillonite powder, 30 g of activated charcoal, and mannitol were given to remove intestinal toxins once a day for five days. The sequential treatment group received 60 g of montmorillonite powder for oral administration, followed by small-volume low-pressure manual gastric lavage with 2.5%bicarbonate liquid. Then 30 g of activated charcoal, 30 g of montmorillonite powder, and polyethylene glycol electrolyte lavage solution were given one after another for gastrointestinal lavage once a day for five days. Both groups received large doses of corticosteroids, blood perfusion, and anti-oxidation treatment. The levels of serum potassium, serum amylase (AMY) alanine aminotransferase (ALT), total bilirubin (TBIL), blood urea nitrogen (BUN), creatinine (Cr), lactate (Lac), and PaO₂of patients were determined at 1, 3, 5, 7, and 10 days. Laxative time, mortality, and survival time of dead cases were evaluated in the two groups. The incidence rates of hypokalemia (<3.5 mmol/L) and AMY (>110 U/L) were significantly lower in the sequential treatment group than in the conventional treatment group (P < 0.05). There were no significant differences in the incidence of ALT (>80 U/L), TBIL (>34.2 µmol/L), BUN (>7.2 mmol/L), and Cr (>177 µmol/L) between the two groups (P>0.05). However, the highest levels of ALT, TBIL, BUN, Cr, and Lac were significantly lower in the sequential treatment group than in the conventional treatment group (P < 0.05). Moreover, the sequential treatment group had significantly lower incidence of PaO₂(<60 mmHg), shorter average laxative time, lower mortality, and longer survival time of dead cases than the conventional treatment group (P < 0.05). The early application of sequential gastrointestinal lavage can shorten laxative time, alleviate organ damage in the liver, kidney, lung, and pancreas, reduce mortality, and prolong the survival time of dead cases in patients with acute paraquat poisoning.

Quantitative proteomic characterization of the lung extracellular matrix in chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis.

PubMed

Åhrman, Emma; Hallgren, Oskar; Malmström, Lars; Hedström, Ulf; Malmström, Anders; Bjermer, Leif; Zhou, Xiao-Hong; Westergren-Thorsson, Gunilla; Malmström, Johan

2018-03-01

Remodeling of the extracellular matrix (ECM) is a common feature in lung diseases such as chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF). Here, we applied a sequential tissue extraction strategy to describe disease-specific remodeling of human lung tissue in disease, using end-stages of COPD and IPF. Our strategy was based on quantitative comparison of the disease proteomes, with specific focus on the matrisome, using data-independent acquisition and targeted data analysis (SWATH-MS). Our work provides an in-depth proteomic characterization of human lung tissue during impaired tissue remodeling. In addition, we show important quantitative and qualitative effects of the solubility of matrisome proteins. COPD was characterized by a disease-specific increase in ECM regulators, metalloproteinase inhibitor 3 (TIMP3) and matrix metalloproteinase 28 (MMP-28), whereas for IPF, impairment in cell adhesion proteins, such as collagen VI and laminins, was most prominent. For both diseases, we identified increased levels of proteins involved in the regulation of endopeptidase activity, with several proteins belonging to the serpin family. The established human lung quantitative proteome inventory and the construction of a tissue-specific protein assay library provides a resource for future quantitative proteomic analyses of human lung tissues. We present a sequential tissue extraction strategy to determine changes in extractability of matrisome proteins in end-stage COPD and IPF compared to healthy control tissue. Extensive quantitative analysis of the proteome changes of the disease states revealed altered solubility of matrisome proteins involved in ECM regulators and cell-ECM communication. The results highlight disease-specific remodeling mechanisms associated with COPD and IPF. Copyright © 2018 Elsevier B.V. All rights reserved.

Transportation forecasting : analysis and quantitative methods

DOT National Transportation Integrated Search

1983-01-01

This Record contains the following papers: Development of Survey Instruments Suitable for Determining Non-Home Activity Patterns; Sequential, History-Dependent Approach to Trip-Chaining Behavior; Identifying Time and History Dependencies of Activity ...

The timing of associative memory formation: frontal lobe and anterior medial temporal lobe activity at associative binding predicts memory

PubMed Central

Hales, J. B.

2011-01-01

The process of associating items encountered over time and across variable time delays is fundamental for creating memories in daily life, such as for stories and episodes. Forming associative memory for temporally discontiguous items involves medial temporal lobe structures and additional neocortical processing regions, including prefrontal cortex, parietal lobe, and lateral occipital regions. However, most prior memory studies, using concurrently presented stimuli, have failed to examine the temporal aspect of successful associative memory formation to identify when activity in these brain regions is predictive of associative memory formation. In the current study, functional MRI data were acquired while subjects were shown pairs of sequentially presented visual images with a fixed interitem delay within pairs. This design allowed the entire time course of the trial to be analyzed, starting from onset of the first item, across the 5.5-s delay period, and through offset of the second item. Subjects then completed a postscan recognition test for the items and associations they encoded during the scan and their confidence for each. After controlling for item-memory strength, we isolated brain regions selectively involved in associative encoding. Consistent with prior findings, increased regional activity predicting subsequent associative memory success was found in anterior medial temporal lobe regions of left perirhinal and entorhinal cortices and in left prefrontal cortex and lateral occipital regions. The temporal separation within each pair, however, allowed extension of these findings by isolating the timing of regional involvement, showing that increased response in these regions occurs during binding but not during maintenance. PMID:21248058

Effector-independent motor sequence representations exist in extrinsic and intrinsic reference frames.

PubMed

Wiestler, Tobias; Waters-Metenier, Sheena; Diedrichsen, Jörn

2014-04-02

Many daily activities rely on the ability to produce meaningful sequences of movements. Motor sequences can be learned in an effector-specific fashion (such that benefits of training are restricted to the trained hand) or an effector-independent manner (meaning that learning also facilitates performance with the untrained hand). Effector-independent knowledge can be represented in extrinsic/world-centered or in intrinsic/body-centered coordinates. Here, we used functional magnetic resonance imaging (fMRI) and multivoxel pattern analysis to determine the distribution of intrinsic and extrinsic finger sequence representations across the human neocortex. Participants practiced four sequences with one hand for 4 d, and then performed these sequences during fMRI with both left and right hand. Between hands, these sequences were equivalent in extrinsic or intrinsic space, or were unrelated. In dorsal premotor cortex (PMd), we found that sequence-specific activity patterns correlated higher for extrinsic than for unrelated pairs, providing evidence for an extrinsic sequence representation. In contrast, primary sensory and motor cortices showed effector-independent representations in intrinsic space, with considerable overlap of the two reference frames in caudal PMd. These results suggest that effector-independent representations exist not only in world-centered, but also in body-centered coordinates, and that PMd may be involved in transforming sequential knowledge between the two. Moreover, although effector-independent sequence representations were found bilaterally, they were stronger in the hemisphere contralateral to the trained hand. This indicates that intermanual transfer relies on motor memories that are laid down during training in both hemispheres, but preferentially draws upon sequential knowledge represented in the trained hemisphere.

Effector-Independent Motor Sequence Representations Exist in Extrinsic and Intrinsic Reference Frames

PubMed Central

Wiestler, Tobias; Waters-Metenier, Sheena

2014-01-01

Many daily activities rely on the ability to produce meaningful sequences of movements. Motor sequences can be learned in an effector-specific fashion (such that benefits of training are restricted to the trained hand) or an effector-independent manner (meaning that learning also facilitates performance with the untrained hand). Effector-independent knowledge can be represented in extrinsic/world-centered or in intrinsic/body-centered coordinates. Here, we used functional magnetic resonance imaging (fMRI) and multivoxel pattern analysis to determine the distribution of intrinsic and extrinsic finger sequence representations across the human neocortex. Participants practiced four sequences with one hand for 4 d, and then performed these sequences during fMRI with both left and right hand. Between hands, these sequences were equivalent in extrinsic or intrinsic space, or were unrelated. In dorsal premotor cortex (PMd), we found that sequence-specific activity patterns correlated higher for extrinsic than for unrelated pairs, providing evidence for an extrinsic sequence representation. In contrast, primary sensory and motor cortices showed effector-independent representations in intrinsic space, with considerable overlap of the two reference frames in caudal PMd. These results suggest that effector-independent representations exist not only in world-centered, but also in body-centered coordinates, and that PMd may be involved in transforming sequential knowledge between the two. Moreover, although effector-independent sequence representations were found bilaterally, they were stronger in the hemisphere contralateral to the trained hand. This indicates that intermanual transfer relies on motor memories that are laid down during training in both hemispheres, but preferentially draws upon sequential knowledge represented in the trained hemisphere. PMID:24695723

Linking high-resolution geomorphic mapping, sediment sources, and channel types in a formerly glaciated basin of northeastern Alto-Adige/Sudtirol, Italy

NASA Astrophysics Data System (ADS)

Brardinoni, F.; Perina, E.; Bonfanti, G.; Falsitta, G.; Agliardi, F.

2012-04-01

To characterize channel-network morphodynamics and response potential in the Gadria-Strimm basin (14.8 km^2) we conduct a concerted effort entailing: (i) high-resolution mapping of landforms, channel reaches, and sediment sources; and (ii) historical evolution of colluvial channel disturbance through sequential aerial photosets (1945-59-69-82-90-00-06-11). The mapping was carried out via stereographic inspection of aerial photographs, examination of 2.5-m gridded DTM and DSM, and extensive field work. The study area is a formerly glaciated basin characterized by peculiar landform assemblages imposed by a combination of tectonic and glacial first-order structures. The most striking feature in Strimm Creek is a structurally-controlled valley step separating an upper hanging valley, dominated by periglacial and fluvial processes, and a V-notched lower part in which lateral colluvial channels are directly connected to Strimm's main stem. In Gadria Creek, massive kame terraces located in proximity of the headwaters provide virtually unlimited sediment supply to frequent debris-flow activity, making this sub-catchment an ideal site for monitoring, hence studying the mechanics of these processes. Preliminary results point to a high spatial variability of the colluvial channel network, in which sub-sectors have remained consistently active during the study period while others have become progressively dormant with notable forest re-growth. In an attempt to link sediment flux to topography and substrate type, future work will involve photogrammetric analysis across the sequential aerial photosets as well as a morphometric/geomechanical characterization of the surficial materials.

Fractionation of enzymatic hydrolysis lignin by sequential extraction for enhancing antioxidant performance.

PubMed

An, Liangliang; Wang, Guanhua; Jia, Hongyu; Liu, Cuiyun; Sui, Wenjie; Si, Chuanling

2017-06-01

The heterogeneity of lignin chemical structure and molecular weight results in the lignin inhomogeneous properties which also covers the antioxidant performance. In order to evaluate the effects of lignin heterogeneity on its antioxidant activity, four lignin fractions from enzymatic hydrolysis lignin were classified by sequential organic solvent extraction and further evaluated by DPPH (1,1-Diphenyl-2-Picrylhydrazyl) free radical scavenging capacity and reducing power analysis. The characterization including FTIR, 1 H NMR and GPC showed that the fractionation process could effectively separate lignin fractions with distinctly different molecular weight and weaken the heterogeneity of unfractionated lignin. The antioxidant performance comparison of lignin fractions indicated that the dichloromethane fraction (F1) with lowest molecular weight (4585g/mol) and highest total phenolics content (246.13mg GAE/g) exhibited the highest antioxidant activity whose value was close to commercial antioxidant BHT (butylated hydroxytoluene). Moreover, the relationship between the antioxidant activity and the structure of lignin was further discussed to elucidate the mechanism of antioxidant activity improvement of lignin fractionation. Consequently, this study suggested that the sequential extraction was an effective way to obtain relatively homogeneous enzymatic hydrolysis lignin fractions which showed the potential for the value-added antioxidant application. Copyright © 2017 Elsevier B.V. All rights reserved.

Aclacinomycin A Sensitizes K562 Chronic Myeloid Leukemia Cells to Imatinib through p38MAPK-Mediated Erythroid Differentiation

PubMed Central

Liu, Fu-Hwa; Huang, Yu-Wen; Huang, Huei-Mei

2013-01-01

Expression of oncogenic Bcr-Abl inhibits cell differentiation of hematopoietic stem/progenitor cells in chronic myeloid leukemia (CML). Differentiation therapy is considered to be a new strategy for treating this type of leukemia. Aclacinomycin A (ACM) is an antitumor antibiotic. Previous studies have shown that ACM induced erythroid differentiation of CML cells. In this study, we investigate the effect of ACM on the sensitivity of human CML cell line K562 to Bcr-Abl specific inhibitor imatinib (STI571, Gleevec). We first determined the optimal concentration of ACM for erythroid differentiation but not growth inhibition and apoptosis in K562 cells. Then, pretreatment with this optimal concentration of ACM followed by a minimally toxic concentration of imatinib strongly induced growth inhibition and apoptosis compared to that with simultaneous co-treatment, indicating that ACM-induced erythroid differentiation sensitizes K562 cells to imatinib. Sequential treatment with ACM and imatinib induced Bcr-Abl down-regulation, cytochrome c release into the cytosol, and caspase-3 activation, as well as decreased Mcl-1 and Bcl-xL expressions, but did not affect Fas ligand/Fas death receptor and procaspase-8 expressions. ACM/imatinib sequential treatment-induced apoptosis was suppressed by a caspase-9 inhibitor and a caspase-3 inhibitor, indicating that the caspase cascade is involved in this apoptosis. Furthermore, we demonstrated that ACM induced erythroid differentiation through the p38 mitogen-activated protein kinase (MAPK) pathway. The inhibition of erythroid differentiation by p38MAPK inhibitor SB202190, p38MAPK dominant negative mutant or p38MAPK shRNA knockdown, reduced the ACM/imatinib sequential treatment-mediated growth inhibition and apoptosis. These results suggest that differentiated K562 cells induced by ACM-mediated p38MAPK pathway become more sensitive to imatinib and result in down-regulations of Bcr-Abl and anti-apoptotic proteins, growth inhibition and apoptosis. These results provided a potential management by which ACM might have a crucial impact on increasing sensitivity of CML cells to imatinib in the differentiation therapeutic approaches. PMID:23613979

Aclacinomycin A sensitizes K562 chronic myeloid leukemia cells to imatinib through p38MAPK-mediated erythroid differentiation.

PubMed

Lee, Yueh-Lun; Chen, Chih-Wei; Liu, Fu-Hwa; Huang, Yu-Wen; Huang, Huei-Mei

2013-01-01

Expression of oncogenic Bcr-Abl inhibits cell differentiation of hematopoietic stem/progenitor cells in chronic myeloid leukemia (CML). Differentiation therapy is considered to be a new strategy for treating this type of leukemia. Aclacinomycin A (ACM) is an antitumor antibiotic. Previous studies have shown that ACM induced erythroid differentiation of CML cells. In this study, we investigate the effect of ACM on the sensitivity of human CML cell line K562 to Bcr-Abl specific inhibitor imatinib (STI571, Gleevec). We first determined the optimal concentration of ACM for erythroid differentiation but not growth inhibition and apoptosis in K562 cells. Then, pretreatment with this optimal concentration of ACM followed by a minimally toxic concentration of imatinib strongly induced growth inhibition and apoptosis compared to that with simultaneous co-treatment, indicating that ACM-induced erythroid differentiation sensitizes K562 cells to imatinib. Sequential treatment with ACM and imatinib induced Bcr-Abl down-regulation, cytochrome c release into the cytosol, and caspase-3 activation, as well as decreased Mcl-1 and Bcl-xL expressions, but did not affect Fas ligand/Fas death receptor and procaspase-8 expressions. ACM/imatinib sequential treatment-induced apoptosis was suppressed by a caspase-9 inhibitor and a caspase-3 inhibitor, indicating that the caspase cascade is involved in this apoptosis. Furthermore, we demonstrated that ACM induced erythroid differentiation through the p38 mitogen-activated protein kinase (MAPK) pathway. The inhibition of erythroid differentiation by p38MAPK inhibitor SB202190, p38MAPK dominant negative mutant or p38MAPK shRNA knockdown, reduced the ACM/imatinib sequential treatment-mediated growth inhibition and apoptosis. These results suggest that differentiated K562 cells induced by ACM-mediated p38MAPK pathway become more sensitive to imatinib and result in down-regulations of Bcr-Abl and anti-apoptotic proteins, growth inhibition and apoptosis. These results provided a potential management by which ACM might have a crucial impact on increasing sensitivity of CML cells to imatinib in the differentiation therapeutic approaches.

Timed sequential chemotherapy of cytoxan-refractory multiple myeloma with cytoxan and adriamycin based on induced tumor proliferation.

PubMed

Karp, J E; Humphrey, R L; Burke, P J

1981-03-01

Malignant plasma cell proliferation and induced humoral stimulatory activity (HSA) occur in vivo at a predictable time following drug administration. Sequential sera from 11 patients with poor-risk multiple myeloma (MM) undergoing treatment with Cytoxan (CY) 2400 mq/sq m were assayed for their in vitro effects on malignant bone marrow plasma cell tritiated thymidine (3HTdR) incorporation. Peak HSA was detected day 9 following CY. Sequential changes in marrow malignant plasma cell 3HTdR-labeling indices (LI) paralleled changes in serum activity, with peak LI occurring at the time of peak HS. An in vitro model of chemotherapy demonstrated that malignant plasma cell proliferation was enhanced by HSA, as determined by 3HTdR incorporation assay, 3HTdR LI, and tumor cells counts, and that stimulated plasma cells were more sensitive to cytotoxic effects of adriamycin (ADR) than were cells cultured in autologous pretreatment serum. Based on these studies, we designed a clinical trial to treat 12 CY-refractory poor-risk patients with MM in which ADR (60 mg/sq m) was administered at the time of peak HSA and residual tumor cell LI (day 9) following initial CY, 2400 mg/m (CY1ADR9). Eight of 12 (67%) responded to timed sequential chemotherapy with a greater than 50% decrement in monoclonal protein marker and a median survival projected to be greater than 8 mo duration (range 4-21+ mo). These clinical results using timed sequential CY1ADR9 compare favorably with results obtained using ADR in nonsequential chemotherapeutic regimens.

Cytokine Expression, Natural Killer Cell Activation, and Phenotypic Changes in Lymphoid Cells from Rhesus Macaques during Acute Infection with Pathogenic Simian Immunodeficiency Virus

PubMed Central

Giavedoni, Luis D.; Velasquillo, M. Cristina; Parodi, Laura M.; Hubbard, Gene B.; Hodara, Vida L.

2000-01-01

We studied the innate and adaptive immune system of rhesus macaques infected with the virulent simian immunodeficiency virus isolate SIVmac251 by evaluating natural killer (NK) cell activity, cytokine levels in plasma, humoral and virological parameters, and changes in the activation markers CD25 (interleukin 2R [IL-2R] α chain), CD69 (early activation marker), and CD154 (CD40 ligand) in lymphoid cells. We found that infection with SIVmac251 induced the sequential production of interferon-α/β (IFN-α/β), IL-18, and IL-12. IFN-γ, IL-4, and granulocyte-macrophage colony-stimulating factor were undetected in plasma by the assays used. NK cell activity peaked at 1 to 2 weeks postinfection and paralleled changes in viral loads. Maximum expression of CD69 on CD3−CD16+ lymphocytes correlated with NK cytotoxicity during this period. CD25 expression, which is associated with proliferation, was static or slightly down-regulated in CD4+ T cells from both peripheral blood (PB) and lymph nodes (LN). CD69, which is normally present in LN CD4+ T cells and absent in peripheral blood leukocyte (PBL) CD4+ T cells, was down-regulated in LN CD4+ T cells and up-regulated in PBL CD4+ T cells immediately after infection. CD8+ T cells increased CD69 but not CD25 expression, indicating the activation of this cellular subset in PB and LN. Finally, CD154 was transiently up-regulated in PBL CD4+ T cells but not in LN CD4+ T cells. Levels of antibodies to SIV Gag and Env did not correlate with the level of activation of CD154, a critical costimulatory molecule for T-cell-dependent immunity. In summary, we present the first documented evidence that the innate immune system of rhesus macaques recognizes SIV infection by sequential production of proinflammatory cytokines and transient activation of NK cytotoxic activity. Additionally, pathogenic SIV induces drastic changes in the level of activation markers on T cells from different anatomic compartments. These changes involve activation in the absence of proliferation, indicating that activation-induced cell death may cause some of the reported increase in lymphocyte turnover during SIV infection. PMID:10644334

Active and Inactive Leg Hemodynamics during Sequential Single-Leg Interval Cycling.

PubMed

Gordon, Nicole; Abbiss, Chris R; Ihsan, Mohammed; Maiorana, Andrew J; Peiffer, Jeremiah J

2018-06-01

Leg order during sequential single-leg cycling (i.e., exercising both legs independently within a single session) may affect local muscular responses potentially influencing adaptations. This study examined the cardiovascular and skeletal muscle hemodynamic responses during double-leg and sequential single-leg cycling. Ten young healthy adults (28 ± 6 yr) completed six 1-min double-leg intervals interspersed with 1 min of passive recovery and, on a separate occasion, 12 (six with one leg followed by six with the other leg) 1-min single-leg intervals interspersed with 1 min of passive recovery. Oxygen consumption, heart rate, blood pressure, muscle oxygenation, muscle blood volume, and power output were measured throughout each session. Oxygen consumption, heart rate, and power output were not different between sets of single-leg intervals, but the average of both sets was lower than the double-leg intervals. Mean arterial pressure was higher during double-leg compared with sequential single-leg intervals (115 ± 9 vs 104 ± 9 mm Hg, P < 0.05) and higher during the initial compared with second set of single-leg intervals (108 ± 10 vs 101 ± 10 mm Hg, P < 0.05). The increase in muscle blood volume from baseline was similar between the active single leg and the double leg (267 ± 150 vs 214 ± 169 μM·cm, P = 0.26). The pattern of change in muscle blood volume from the initial to second set of intervals was significantly different (P < 0.05) when the leg was active in the initial (-52.3% ± 111.6%) compared with second set (65.1% ± 152.9%). These data indicate that the order in which each leg performs sequential single-leg cycling influences the local hemodynamic responses, with the inactive muscle influencing the stimulus experienced by the contralateral leg.

Transforming growth factor-{beta} inhibits CCAAT/enhancer-binding protein expression and PPAR{gamma} activity in unloaded bone marrow stromal cells

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

Ahdjoudj, S.; Kaabeche, K.; Holy, X.

2005-02-01

The molecular mechanisms regulating the adipogenic differentiation of bone marrow stromal cells in vivo remain largely unknown. In this study, we investigated the regulatory effects of transforming growth factor beta-2 (TGF-{beta}2) on transcription factors involved in adipogenic differentiation induced by hind limb suspension in rat bone marrow stromal cells in vivo. Time course real-time quantitative reverse-transcription polymerase chain reaction (RT-PCR) analysis of gene expression showed that skeletal unloading progressively increases the expression of CCAAT/enhancer-binding protein (C/EBP){alpha} and C/EBP{beta} {alpha} at 5 days in bone marrow stromal cells resulting in increased peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}2) transcripts at 7 days. TGF-{beta}2more » administration in unloaded rats corrected the rise in C/EBP{alpha} and C/EBP{beta} transcripts induced by unloading in bone marrow stromal cells. This resulted in inhibition of PPAR{gamma}2 expression that was associated with increased Runx2 expression. Additionally, the inhibition of C/EBP{alpha} and C/EBP{beta} expression by TGF-{beta}2 was associated with increased PPAR{gamma} serine phosphorylation in bone marrow stromal cells, a mechanism that inhibits PPAR{gamma} transactivating activity. The sequential inhibitory effect of TGF-{beta}2 on C/EBP{alpha}, C/EBP{beta}, and PPAR{gamma}2 resulted in reduced LPL expression and abolition of bone marrow stromal cell adipogenic differentiation, which contributed to prevent bone loss induced by skeletal unloading. We conclude that TGF-{beta}2 inhibits the excessive adipogenic differentiation of bone marrow stromal cells induced by skeletal unloading by inhibiting C/EBP{alpha}, C/EBP{beta}, and PPAR{gamma} expression and activity, which provides a sequential mechanism by which TGF-{beta}2 regulates adipogenic differentiation of bone marrow stromal cells in vivo.« less

Use of endogenous cortisol 6β-hydroxylation clearance for phenotyping in vivo CYP3A activity in women after sequential administration of an oral contraceptive (OC) containing ethinylestradiol and levonorgestrel as weak CYP3A inhibitors.

PubMed

Shibasaki, Hiromi; Kuroiwa, Miyuki; Uchikura, Shinobu; Tsuboyama, Sayuri; Yokokawa, Akitomo; Kume, Miyoko; Furuta, Takashi

2014-09-01

The present study was undertaken to evaluate the time courses of in vivo cytochrome P450 3A (CYP3A) inhibition in four healthy women after sequential administration of an oral contraceptive (OC) containing ethinylestradiol and levonorgestrel, using 6β-hydroxylation clearance of endogenous cortisol (CLm(6β)) as a new index for CYP3A phenotyping. The 6β-hydroxylation clearance (CLm(6β)) was followed every 2h from 9:00 or 11:00 to 17:00 on days 0 (baseline), 1, 2, 21, and 28 during a single menstrual cycle. The serum concentrations of endogenous estradiol and progesterone were also measured. The time course data of CLm(6β) clearly demonstrated 43-64% inhibition of CYP3A activity in women taking a low daily dose of the OC for 21days. The average CLm(6β) levels that were suppressed by the OC in four women were extremely low (0.60-1.23mL/min) compared with the normal CLm(6β) range (1.5-3.5mL/min) that was obtained from 49 healthy subjects in our previous study. The in vivo inhibitory potencies (43-64%) obtained in this study were stronger than expected from reported in vitro studies (∼20%). Furthermore, it would take at least seven days to return to the baseline activity of CYP3A after discontinuation of the OC. The results presented here should provide important information on the inhibitory effect of OC on the CYP3A activities in women, which are involved in the metabolism of a number of drugs with a narrow therapeutic range. Copyright © 2014 Elsevier Inc. All rights reserved.

Exploring the mechanistic insights of Cas scaffolding protein family member 4 with protein tyrosine kinase 2 in Alzheimer's disease by evaluating protein interactions through molecular docking and dynamic simulations.

PubMed

Hassan, Mubashir; Shahzadi, Saba; Alashwal, Hany; Zaki, Nazar; Seo, Sung-Yum; Moustafa, Ahmed A

2018-05-22

Cas scaffolding protein family member 4 and protein tyrosine kinase 2 are signaling proteins, which are involved in neuritic plaques burden, neurofibrillary tangles, and disruption of synaptic connections in Alzheimer's disease. In the current study, a computational approach was employed to explore the active binding sites of Cas scaffolding protein family member 4 and protein tyrosine kinase 2 proteins and their significant role in the activation of downstream signaling pathways. Sequential and structural analyses were performed on Cas scaffolding protein family member 4 and protein tyrosine kinase 2 to identify their core active binding sites. Molecular docking servers were used to predict the common interacting residues in both Cas scaffolding protein family member 4 and protein tyrosine kinase 2 and their involvement in Alzheimer's disease-mediated pathways. Furthermore, the results from molecular dynamic simulation experiment show the stability of targeted proteins. In addition, the generated root mean square deviations and fluctuations, solvent-accessible surface area, and gyration graphs also depict their backbone stability and compactness, respectively. A better understanding of CAS and their interconnected protein signaling cascade may help provide a treatment for Alzheimer's disease. Further, Cas scaffolding protein family member 4 could be used as a novel target for the treatment of Alzheimer's disease by inhibiting the protein tyrosine kinase 2 pathway.

Paf receptor expression in the marsupial embryo and endometrium during embryonic diapause.

PubMed

Fenelon, Jane C; Shaw, Geoff; O'Neill, Chris; Frankenberg, Stephen; Renfree, Marilyn B

2014-01-01

The control of reactivation from embryonic diapause in the tammar wallaby (Macropus eugenii) involves sequential activation of the corpus luteum, secretion of progesterone that stimulates endometrial secretion and subsequent changes in the uterine environment that activate the embryo. However, the precise signals between the endometrium and the blastocyst are currently unknown. In eutherians, both the phospholipid Paf and its receptor, platelet-activating factor receptor (PTAFR), are present in the embryo and the endometrium. In the tammar, endometrial Paf release in vitro increases around the time of the early progesterone pulse that occurs around the time of reactivation, but whether Paf can reactivate the blastocyst is unknown. We cloned and characterised the expression of PTAFR in the tammar embryo and endometrium at entry into embryonic diapause, during its maintenance and after reactivation. Tammar PTAFR sequence and protein were highly conserved with mammalian orthologues. In the endometrium, PTAFR was expressed at a constant level in the glandular epithelium across all stages and in the luminal epithelium during both diapause and reactivation. Thus, the presence of the receptor appears not to be a limiting factor for Paf actions in the endometrium. However, the low levels of PTAFR in the embryo during diapause, together with its up-regulation and subsequent internalisation at reactivation, supports earlier results suggesting that endometrial Paf could be involved in reactivation of the tammar blastocyst from embryonic diapause.

The architecture of visual narrative comprehension: the interaction of narrative structure and page layout in understanding comics

PubMed Central

Cohn, Neil

2014-01-01

How do people make sense of the sequential images in visual narratives like comics? A growing literature of recent research has suggested that this comprehension involves the interaction of multiple systems: The creation of meaning across sequential images relies on a “narrative grammar” that packages conceptual information into categorical roles organized in hierarchic constituents. These images are encapsulated into panels arranged in the layout of a physical page. Finally, how panels frame information can impact both the narrative structure and page layout. Altogether, these systems operate in parallel to construct the Gestalt whole of comprehension of this visual language found in comics. PMID:25071651

Orthographic Structure and Reading Experience Affect the Transfer from Iconic to Short Term Memory

ERIC Educational Resources Information Center

Lefton, Lester A.; Spragins, Anne B.

1974-01-01

The basic hypothesis of these experiments was that the processing strategy for the transfer of alphabetic material from iconic storage to short-term memory involves a sequential left-to-right factor that develops with increases in experience with reading. (Author)

It's Deja Vu All over Again: Using Multiple-Spell Discrete-Time Survival Analysis.

ERIC Educational Resources Information Center

Willett, John B.; Singer, Judith D.

1995-01-01

The multiple-spell discrete-time survival analysis method is introduced and illustrated using longitudinal data on exit from and reentry into the teaching profession. The method is applicable to many educational problems involving the sequential occurrence of disparate events or episodes. (SLD)

Towards efficient multi-scale methods for monitoring sugarcane aphid infestations in sorghum

USDA-ARS?s Scientific Manuscript database

We discuss approaches and issues involved with developing optimal monitoring methods for sugarcane aphid infestations (SCA) in grain sorghum. We discuss development of sequential sampling methods that allow for estimation of the number of aphids per sample unit, and statistical decision making rela...

A Rationale for Developmental Testing and Training.

ERIC Educational Resources Information Center

Arner, Robert S.

Man's phylogenetic development has resulted in a potential for environmental interaction in a symbolic and conceptual manner. There are ontogenetic requirements to develop such potential. The process by which man learns is sequential and involves perceptual-motor-cognitive abilities. There is an optimum respectivity period at each developmental…

The Inner Processes Underlying Vocational Development.

ERIC Educational Resources Information Center

Bujold, Charles E.; And Others

Educational and occupational choices may be considered, from a developmental point of view, as long-term problems whose solutions imply a number of tasks. These tasks sequentially might be called exploration, crystallization, specification, and implementation. What are the processes involved in these tasks? What are the abilities which make…

Mixed-Methods Research Methodologies

ERIC Educational Resources Information Center

Terrell, Steven R.

2012-01-01

Mixed-Method studies have emerged from the paradigm wars between qualitative and quantitative research approaches to become a widely used mode of inquiry. Depending on choices made across four dimensions, mixed-methods can provide an investigator with many design choices which involve a range of sequential and concurrent strategies. Defining…

A fully resolved fluid-structure-muscle-activation model for esophageal transport

NASA Astrophysics Data System (ADS)

Kou, Wenjun; Bhalla, Amneet P. S.; Griffith, Boyce E.; Johnson, Mark; Patankar, Neelesh A.

2013-11-01

Esophageal transport is a mechanical and physiological process that transfers the ingested food bolus from the pharynx to the stomach through a multi-layered esophageal tube. The process involves interactions between the bolus, esophageal wall composed of mucosal, circular muscle (CM) and longitudinal muscle (LM) layers, and neurally coordinated muscle activation including CM contraction and LM shortening. In this work, we present a 3D fully-resolved model of esophageal transport based on the immersed boundary method. The model describes the bolus as a Newtonian fluid, the esophageal wall as a multi-layered elastic tube represented by springs and beams, and the muscle activation as a traveling wave of sequential actuation/relaxation of muscle fibers, represented by springs with dynamic rest lengths. Results on intraluminal pressure profile and bolus shape will be shown, which are qualitatively consistent with experimental observations. Effects of activating CM contraction only, LM shortening only or both, for the bolus transport, are studied. A comparison among them can help to identify the role of each type of muscle activation. The support of grant R01 DK56033 and R01 DK079902 from NIH is gratefully acknowledged.

Inhibition of epithelial Na sup + transport by atriopeptin, protein kinase c, and pertussis toxin

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

Mohrmann, M.; Cantiello, H.F.; Ausiello, D.A.

1987-08-01

The authors have recently shown the selective inhibition of an amiloride-sensitive, conductive pathway for Na{sup +} by atrial natriuretic peptide and 8-bromoguanosine 3{prime},5{prime}-cyclic monophosphate (8-BrcGMP) in the renal epithelial cell line, LLC-PK{sub i}. Using {sup 22}Na{sup +} fluxes, they further investigated the modulation of Na{sup +} transport by atrial natriuretic peptide and by agents that increase cGMP production, activate protein kinase c, or modulate guanine nucleotide regulatory protein function. Sodium nitroprusside increases intracellular cGMP concentrations without affecting cAMP concentrations and completely inhibits amiloride-sensitive Na{sup +} uptake in a time- and concentration-dependent manner. Oleoyl 2-acetylglycerol and phorbol 12-myristate 13-acetate, activators ofmore » protein kinase c, inhibit Na{sup +} uptake by 93 {plus minus} 13 and 51 {plus minus} 10%, respectively. Prolonged incubation with phorbol ester results in the downregulation of protein kinase c activity and reduces the inhibitory effect of atrial natriuretic peptide, suggesting that the action of this peptide involves stimulation of protein kinase c. Pertussis toxin, which induces the ADP-ribosylation of a 41-kDa guanine nucleotide regulatory protein in LLC-PK{sub i} cells, inhibits {sup 22}Na{sup +} influx to the same extent as amiloride. Thus, increasing cGMP, activating protein kinase c, and ADP-ribosylating a guanine nucleotide regulatory protein all inhibit Na{sup +} uptake. These events may be sequentially involved in the action of atrial natriuretic peptide.« less

Predictive Place-Cell Sequences for Goal-Finding Emerge from Goal Memory and the Cognitive Map: A Computational Model

PubMed Central

Gönner, Lorenz; Vitay, Julien; Hamker, Fred H.

2017-01-01

Hippocampal place-cell sequences observed during awake immobility often represent previous experience, suggesting a role in memory processes. However, recent reports of goals being overrepresented in sequential activity suggest a role in short-term planning, although a detailed understanding of the origins of hippocampal sequential activity and of its functional role is still lacking. In particular, it is unknown which mechanism could support efficient planning by generating place-cell sequences biased toward known goal locations, in an adaptive and constructive fashion. To address these questions, we propose a model of spatial learning and sequence generation as interdependent processes, integrating cortical contextual coding, synaptic plasticity and neuromodulatory mechanisms into a map-based approach. Following goal learning, sequential activity emerges from continuous attractor network dynamics biased by goal memory inputs. We apply Bayesian decoding on the resulting spike trains, allowing a direct comparison with experimental data. Simulations show that this model (1) explains the generation of never-experienced sequence trajectories in familiar environments, without requiring virtual self-motion signals, (2) accounts for the bias in place-cell sequences toward goal locations, (3) highlights their utility in flexible route planning, and (4) provides specific testable predictions. PMID:29075187

Heterogeneous Semiconductor Shells Sequentially Coated on Upconversion Nanoplates for NIR-Light Enhanced Photocatalysis.

PubMed

Cui, Cao; Tou, Meijie; Li, Mohua; Luo, Zhenguo; Xiao, Lingbo; Bai, Song; Li, Zhengquan

2017-02-20

Combination of upconversion nanocrystals (UCNs) with CeO 2 is a decent choice to construct NIR-activated photocatalysts for utilizing the NIR light in the solar spectrum. Herein we present a facile approach to deposit a CeO 2 layer with controllable thickness on the plate-shaped NaYF 4 :Yb,Tm UCNs. The developed core-shell nanocomposites display obvious photocatalytic activity under the NIR light and exhibit enhanced activity under the full solar spectrum. For enhancing the separation of photogenerated electrons and holes on the CeO 2 surface, we sequentially coat a ZnO shell on the nanocomposites so as to form a heterojunction structure for achieving a better activity. The developed hybrid photocatalysts have been characterized with TEM, SEM, PL, etc., and the working mechanism of such UCN-semiconductor heterojunction photocatalysts has been proposed.

Bioactive Lipidic Extracts from Octopus (Paraoctopus limaculatus): Antimutagenicity and Antiproliferative Studies

PubMed Central

Moreno-Félix, Carolina; Wilson-Sánchez, Griselda; Cruz-Ramírez, Susana-Gabriela; Velázquez-Contreras, Carlos; Plascencia-Jatomea, Maribel; Acosta, Ana; Machi-Lara, Lorena; Aldana-Madrid, María-Lourdes; Ezquerra-Brauer, Josafat-Marina; Rocha-Alonzo, Fernando; Burgos-Hernández, Armando

2013-01-01

Fractions from an organic extract from fresh octopus (Paraoctopus limaculatus) were studied for biological activities such as antimutagenic and antiproliferative properties using Salmonella tester strains TA98 and TA100 with metabolic activation (S9) and a cancer cell line (B-cell lymphoma), respectively. A chloroform extract obtained from octopus tentacles was sequentially fractionated using thin layer chromatography (TLC), and each fraction was tested for antimutagenic and antiproliferative activities. Organic extract reduced the number of revertants caused by aflatoxin B1 showing a dose-response type of relationship. Sequential TLC fractionation of the active extracts produced several antimutagenic and/or antiproliferative fractions. Based on the results obtained, the isolated fractions obtained from octopus contain compounds with chemoprotective properties that reduce the mutagenicity of AFB1 and proliferation of cancer cell lines. PMID:23401709

Design and protocol of a randomized multiple behavior change trial: Make Better Choices 2 (MBC2).

PubMed

Pellegrini, Christine A; Steglitz, Jeremy; Johnston, Winter; Warnick, Jennifer; Adams, Tiara; McFadden, H G; Siddique, Juned; Hedeker, Donald; Spring, Bonnie

2015-03-01

Suboptimal diet and inactive lifestyle are among the most prevalent preventable causes of premature death. Interventions that target multiple behaviors are potentially efficient; however the optimal way to initiate and maintain multiple health behavior changes is unknown. The Make Better Choices 2 (MBC2) trial aims to examine whether sustained healthful diet and activity change are best achieved by targeting diet and activity behaviors simultaneously or sequentially. Study design approximately 250 inactive adults with poor quality diet will be randomized to 3 conditions examining the best way to prescribe healthy diet and activity change. The 3 intervention conditions prescribe: 1) an increase in fruit and vegetable consumption (F/V+), decrease in sedentary leisure screen time (Sed-), and increase in physical activity (PA+) simultaneously (Simultaneous); 2) F/V+ and Sed- first, and then sequentially add PA+ (Sequential); or 3) Stress Management Control that addresses stress, relaxation, and sleep. All participants will receive a smartphone application to self-monitor behaviors and regular coaching calls to help facilitate behavior change during the 9 month intervention. Healthy lifestyle change in fruit/vegetable and saturated fat intakes, sedentary leisure screen time, and physical activity will be assessed at 3, 6, and 9 months. MBC2 is a randomized m-Health intervention examining methods to maximize initiation and maintenance of multiple healthful behavior changes. Results from this trial will provide insight about an optimal technology supported approach to promote improvement in diet and physical activity. Copyright © 2015 Elsevier Inc. All rights reserved.

Fibrin-specific and effective clot lysis requires both plasminogen activators and for them to be in a sequential rather than simultaneous combination.

PubMed

Pannell, R; Li, S; Gurewich, V

2017-08-01

Thrombolysis with tissue plasminogen activator (tPA) has been a disappointment and has now been replaced by an endovascular procedure whenever possible. Nevertheless, thrombolysis remains the only means by which circulation in a thrombosed artery can be restored rapidly. In contrast to tPA monotherapy, endogenous fibrinolysis uses both tPA and urokinase plasminogen activator (uPA), whose native form is a proenzyme, prouPA. This combination is remarkably effective as evidenced by the fibrin degradation product, D-dimer, which is invariably present in plasma. The two activators have complementary mechanisms of plasminogen activation and are synergistic in combination. Since tPA initiates fibrinolysis when released from the vessel wall and prouPA is in the blood, they induce fibrinolysis sequentially. It was postulated that this may be more effective and fibrin-specific. The hypothesis was tested in a model of clot lysis in plasma in which a clot was first exposed to tPA for 5 min, washed and incubated with prouPA. Lysis was compared with that of clots incubated with both activators simultaneously. The sequential combination was almost twice as effective and caused less fibrinogenolysis than the simultaneous combination (p < 0.0001) despite having significantly less tPA, as a result of the wash. A mechanism is described by which this phenomenon can be explained. The findings are believed to have significant therapeutic implications.

Extracellular annexins and dynamin are important for sequential steps in myoblast fusion

PubMed Central

Leikina, Evgenia; Melikov, Kamran; Sanyal, Sarmistha; Verma, Santosh K.; Eun, Bokkee; Gebert, Claudia; Pfeifer, Karl; Lizunov, Vladimir A.; Kozlov, Michael M.

2013-01-01

Myoblast fusion into multinucleated myotubes is a crucial step in skeletal muscle development and regeneration. Here, we accumulated murine myoblasts at the ready-to-fuse stage by blocking formation of early fusion intermediates with lysophosphatidylcholine. Lifting the block allowed us to explore a largely synchronized fusion. We found that initial merger of two cell membranes detected as lipid mixing involved extracellular annexins A1 and A5 acting in a functionally redundant manner. Subsequent stages of myoblast fusion depended on dynamin activity, phosphatidylinositol(4,5)bisphosphate content, and cell metabolism. Uncoupling fusion from preceding stages of myogenesis will help in the analysis of the interplay between protein machines that initiate and complete cell unification and in the identification of additional protein players controlling different fusion stages. PMID:23277424

Electrooxidation of morin hydrate at a Pt electrode studied by cyclic voltammetry.

PubMed

Masek, Anna; Chrzescijanska, Ewa; Zaborski, Marian

2014-04-01

The process and the kinetics of the electrochemical oxidation of morin in an anhydrous electrolyte have been investigated using cyclic and differential pulse voltammetry. The oxidation mechanism proceeds in sequential steps related to the hydroxyl groups in the three aromatic rings. The oxidation of the 2',4'dihydroxy moiety at the B ring of morin occurs first, at very low positive potentials, and is a one-electron, one-proton irreversible reaction. The rate constant, electron transfer coefficient and diffusion coefficients involved in the electrochemical oxidation of morin were determined. The influence of the deprotonation of the ring B hydroxyl moiety is related to the electron/proton donating capacity of morin and to its radical scavenging antioxidant activity. Copyright © 2013 Elsevier Ltd. All rights reserved.

Allosteric substrate switching in a voltage-sensing lipid phosphatase.

PubMed

Grimm, Sasha S; Isacoff, Ehud Y

2016-04-01

Allostery provides a critical control over enzyme activity, biasing the catalytic site between inactive and active states. We found that the Ciona intestinalis voltage-sensing phosphatase (Ci-VSP), which modifies phosphoinositide signaling lipids (PIPs), has not one but two sequential active states with distinct substrate specificities, whose occupancy is allosterically controlled by sequential conformations of the voltage-sensing domain (VSD). Using fast fluorescence resonance energy transfer (FRET) reporters of PIPs to monitor enzyme activity and voltage-clamp fluorometry to monitor conformational changes in the VSD, we found that Ci-VSP switches from inactive to a PIP3-preferring active state when the VSD undergoes an initial voltage-sensing motion and then into a second PIP2-preferring active state when the VSD activates fully. This two-step allosteric control over a dual-specificity enzyme enables voltage to shape PIP concentrations in time, and provides a mechanism for the complex modulation of PIP-regulated ion channels, transporters, cell motility, endocytosis and exocytosis.

Allosteric substrate switching in a voltage sensing lipid phosphatase

PubMed Central

Grimm, Sasha S.; Isacoff, Ehud Y.

2016-01-01

Allostery provides a critical control over enzyme activity, biasing the catalytic site between inactive and active states. We find the Ciona intestinalis voltage-sensing phosphatase (Ci-VSP), which modifies phosphoinositide signaling lipids (PIPs), to have not one but two sequential active states with distinct substrate specificities, whose occupancy is allosterically controlled by sequential conformations of the voltage sensing domain (VSD). Using fast FRET reporters of PIPs to monitor enzyme activity and voltage clamp fluorometry to monitor conformational changes in the VSD, we find that Ci-VSP switches from inactive to a PIP3-preferring active state when the VSD undergoes an initial voltage sensing motion and then into a second PIP2-preferring active state when the VSD activates fully. This novel 2-step allosteric control over a dual specificity enzyme enables voltage to shape PIP concentrations in time, and provides a mechanism for the complex modulation of PIP-regulated ion channels, transporters, cell motility and endo/exocytosis. PMID:26878552

Involving members of vulnerable populations in the development of patient decision aids: a mixed methods sequential explanatory study.

PubMed

Dugas, Michèle; Trottier, Marie-Ève; Chipenda Dansokho, Selma; Vaisson, Gratianne; Provencher, Thierry; Colquhoun, Heather; Dogba, Maman Joyce; Dupéré, Sophie; Fagerlin, Angela; Giguere, Anik M C; Haslett, Lynne; Hoffman, Aubri S; Ivers, Noah M; Légaré, France; Légaré, Jean; Levin, Carrie A; Menear, Matthew; Renaud, Jean-Sébastien; Stacey, Dawn; Volk, Robert J; Witteman, Holly O

2017-01-19

Patient decision aids aim to present evidence relevant to a health decision in understandable ways to support patients through the process of making evidence-informed, values-congruent health decisions. It is recommended that, when developing these tools, teams involve people who may ultimately use them. However, there is little empirical evidence about how best to undertake this involvement, particularly for specific populations of users such as vulnerable populations. To describe and compare the development practices of research teams that did and did not specifically involve members of vulnerable populations in the development of patient decision aids, we conducted a secondary analysis of data from a systematic review about the development processes of patient decision aids. Then, to further explain our quantitative results, we conducted semi-structured telephone interviews with 10 teams: 6 that had specifically involved members of vulnerable populations and 4 that had not. Two independent analysts thematically coded transcribed interviews. Out of a total of 187 decision aid development projects, 30 (16%) specifically involved members of vulnerable populations. The specific involvement of members of vulnerable populations in the development process was associated with conducting informal needs assessment activities (73% vs. 40%, OR 2.96, 95% CI 1.18-7.99, P = .02) and recruiting participants through community-based organizations (40% vs. 11%, OR 3.48, 95% CI 1.23-9.83, P = .02). In interviews, all developers highlighted the importance, value and challenges of involving potential users. Interviews with developers whose projects had involved members of vulnerable populations suggested that informal needs assessment activities served to center the decision aid around users' needs, to better avoid stigma, and to ensure that the topic truly matters to the community. Partnering with community-based organizations may facilitate relationships of trust and may also provide a non-threatening and accessible location for research activities. There are a small number of key differences in the development processes for patient decision aids in which members of vulnerable populations were or were not specifically involved. Some of these practices may require additional time or resources. To address health inequities, researchers, communities and funders may need to increase awareness of these approaches and plan accordingly.

Tuning the Brake While Raising the Stake: Network Dynamics during Sequential Decision-Making.

PubMed

Meder, David; Haagensen, Brian Numelin; Hulme, Oliver; Morville, Tobias; Gelskov, Sofie; Herz, Damian Marc; Diomsina, Beata; Christensen, Mark Schram; Madsen, Kristoffer Hougaard; Siebner, Hartwig Roman

2016-05-11

When gathering valued goods, risk and reward are often coupled and escalate over time, for instance, during foraging, trading, or gambling. This escalating frame requires agents to continuously balance expectations of reward against those of risk. To address how the human brain dynamically computes these tradeoffs, we performed whole-brain fMRI while healthy young individuals engaged in a sequential gambling task. Participants were repeatedly confronted with the option to continue with throwing a die to accumulate monetary reward under escalating risk, or the alternative option to stop to bank the current balance. Within each gambling round, the accumulation of gains gradually increased reaction times for "continue" choices, indicating growing uncertainty in the decision to continue. Neural activity evoked by "continue" choices was associated with growing activity and connectivity of a cortico-subcortical "braking" network that positively scaled with the accumulated gains, including pre-supplementary motor area (pre-SMA), inferior frontal gyrus, caudate, and subthalamic nucleus (STN). The influence of the STN on continue-evoked activity in the pre-SMA was predicted by interindividual differences in risk-aversion attitudes expressed during the gambling task. Furthermore, activity in dorsal anterior cingulate cortex (ACC) reflected individual choice tendencies by showing increased activation when subjects made nondefault "continue" choices despite an increasing tendency to stop, but ACC activity did not change in proportion with subjective choice uncertainty. Together, the results implicate a key role of dorsal ACC, pre-SMA, inferior frontal gyrus, and STN in computing the trade-off between escalating reward and risk in sequential decision-making. Using a paradigm where subjects experienced increasing potential rewards coupled with increasing risk, this study addressed two unresolved questions in the field of decision-making: First, we investigated an "inhibitory" network of regions that has so far been investigated with externally cued action inhibition. In this study, we show that the dynamics in this network under increasingly risky decisions are predictive of subjects' risk attitudes. Second, we contribute to a currently ongoing debate about the anterior cingulate cortex's role in sequential foraging decisions by showing that its activity is related to making nondefault choices rather than to choice uncertainty. Copyright © 2016 Meder, Haagensen, et al.

Sequential chemical treatment of radium species in TENORM waste sludge produced from oil and natural gas production.

PubMed

El Afifi, E M; Awwad, N S; Hilal, M A

2009-01-30

This paper is dedicated to the treatment of sludge occurring in frame of the Egyptian produced from oil and gas production. The activity levels of three radium isotopes: Ra-226 (of U-series), Ra-228 and Ra-224 (of Th-series) in the solid TENORM waste (sludge) were first evaluated and followed by a sequential treatment for all radium species (fractions) presented in TENORM. The sequential treatment was carried out based on two approaches 'A' and 'B' using different chemical solutions. The results obtained indicate that the activity levels of all radium isotopes (Ra-226, Ra-228 and Ra-224) of the environmental interest in the TENORM waste sludge were elevated with regard to exemption levels established by IAEA [International Atomic Energy Agency (IAEA), International basic safety standards for the protection against ionizing radiation and for the safety of radiation sources. GOV/2715/Vienna, 1994]. Each approach of the sequential treatment was performed through four steps using different chemical solutions to reduce the activity concentration of radium in a large extent. Most of the leached radium was found as an oxidizable Ra species. The actual removal % leached using approach B was relatively efficient compared to A. It is observed that the actual removal percentages (%) of Ra-226, Ra-228 and Ra-224 using approach A are 78+/-2.8, 64.8+/-4.1 and 76.4+/-5.2%, respectively. Whereas in approach A, the overall removal % of Ra-226, Ra-228 and Ra-228 was increased to approximately 91+/-3.5, 87+/-4.1 and 90+/-6.2%, respectively.

Microwave Ablation: Comparison of Simultaneous and Sequential Activation of Multiple Antennas in Liver Model Systems

PubMed Central

Harari, Colin M.; Magagna, Michelle; Bedoya, Mariajose; Lee, Fred T.; Lubner, Meghan G.; Hinshaw, J. Louis; Ziemlewicz, Timothy

2016-01-01

Purpose To compare microwave ablation zones created by using sequential or simultaneous power delivery in ex vivo and in vivo liver tissue. Materials and Methods All procedures were approved by the institutional animal care and use committee. Microwave ablations were performed in both ex vivo and in vivo liver models with a 2.45-GHz system capable of powering up to three antennas simultaneously. Two- and three-antenna arrays were evaluated in each model. Sequential and simultaneous ablations were created by delivering power (50 W ex vivo, 65 W in vivo) for 5 minutes per antenna (10 and 15 minutes total ablation time for sequential ablations, 5 minutes for simultaneous ablations). Thirty-two ablations were performed in ex vivo bovine livers (eight per group) and 28 in the livers of eight swine in vivo (seven per group). Ablation zone size and circularity metrics were determined from ablations excised postmortem. Mixed effects modeling was used to evaluate the influence of power delivery, number of antennas, and tissue type. Results On average, ablations created by using the simultaneous power delivery technique were larger than those with the sequential technique (P < .05). Simultaneous ablations were also more circular than sequential ablations (P = .0001). Larger and more circular ablations were achieved with three antennas compared with two antennas (P < .05). Ablations were generally smaller in vivo compared with ex vivo. Conclusion The use of multiple antennas and simultaneous power delivery creates larger, more confluent ablations with greater temperatures than those created with sequential power delivery. © RSNA, 2015 PMID:26133361

Modified ecometric technique (four-quadrant sequential streak) to evaluate Campylobacter enrichment broth proficiency in suppressing background microflora

USDA-ARS?s Scientific Manuscript database

Ecometric technique is a semi-quantitative scoring method used for quality control of culture media in microbiological laboratories. The technique involves inoculation with defined populations of specific culture onto solid media via a standardized chronological streaking technique, leading to ever-...

Enacting Power Asymmetries in Reported Exchanges in the Narratives of Former Slaves

ERIC Educational Resources Information Center

Van De Mieroop, Dorien; Clifton, Jonathan

2013-01-01

Direct reported speech has been described as serving many functions in stories, such as increasing vividness, creating authenticity, and enhancing audience involvement. Drawing on Bamberg's model of positioning and focusing on reported exchanges, we argue that through its "constructed sequentiality" and its use of discourse strategies, direct…

Ecdysteroid biosynthesis in varroa mites: identification of halloween genes from the biosynthetic pathway and their regulation during reproduction

USDA-ARS?s Scientific Manuscript database

Biosynthesis of ecdysteroids involves sequential enzymatic hydroxylations by microsomal enzymes and mitochondrial cytochrome P450’s. Enzymes of the pathway are collectively known as Halloween genes. Complete sequences for three Halloween genes, spook (Vdspo), disembodied (Vddib) and shade (Vdshd), w...

An Adaptable Investigative Graduate Laboratory Course for Teaching Protein Purification

ERIC Educational Resources Information Center

Carroll, Christopher W.; Keller, Lani C.

2014-01-01

This adaptable graduate laboratory course on protein purification offers students the opportunity to explore a wide range of techniques while allowing the instructor the freedom to incorporate their own personal research interests. The course design involves two sequential purification schemes performed in a single semester. The first part…

Exact Tests for the Rasch Model via Sequential Importance Sampling

ERIC Educational Resources Information Center

Chen, Yuguo; Small, Dylan

2005-01-01

Rasch proposed an exact conditional inference approach to testing his model but never implemented it because it involves the calculation of a complicated probability. This paper furthers Rasch's approach by (1) providing an efficient Monte Carlo methodology for accurately approximating the required probability and (2) illustrating the usefulness…

Testing an Integrated Model of Advice Giving in Supportive Interactions

ERIC Educational Resources Information Center

Feng, Bo

2009-01-01

Viewing supportive communication as a multistage process, the present study proposed and tested an integrated model of advice giving, which specifies three sequential moves in supportive interactions involving advice: emotional support, problem inquiry and analysis, and advice. Seven hundred and fifty-two participants read and responded to a…

ASPEN Plus in the Chemical Engineering Curriculum: Suitable Course Content and Teaching Methodology

ERIC Educational Resources Information Center

Rockstraw, David A.

2005-01-01

An established methodology involving the sequential presentation of five skills on ASPEN Plus to undergraduate seniors majoring in ChE is presented in this document: (1) specifying unit operations; (2) manipulating physical properties; (3) accessing variables; (4) specifying nonstandard components; and (5) applying advanced features. This…

The Structure of Visuospatial Memory in Adulthood

ERIC Educational Resources Information Center

Mammarella, Irene C.; Borella, Erika; Pastore, Massimiliano; Pazzaglia, Francesca

2013-01-01

The present study aimed to investigate the structure of visuospatial memory in adulthood. Adults 40-89 years of age (n = 160) performed simple storage and complex visuospatial span tasks. Simple storage tasks were distinguished into three presentation formats: (i) visual, which involved maintaining shapes and textures; (ii) spatial-sequential,…

Development of Type 1 Diabetes Mellitus in Nonobese Diabetic Mice Follows Changes in Thymocyte and Peripheral T Lymphocyte Transcriptional Activity

PubMed Central

Fornari, Thais A.; Donate, Paula B.; Macedo, Claudia; Sakamoto-Hojo, Elza T.; Donadi, Eduardo A.; Passos, Geraldo A.

2011-01-01

As early as one month of age, nonobese diabetic (NOD) mice feature pancreatic infiltration of autoreactive T lymphocytes, which destruct insulin-producing beta cells, producing autoimmune diabetes mellitus (T1D) within eight months. Thus, we hypothesized that during the development of T1D, the transcriptional modulation of immune reactivity genes may occur as thymocytes mature into peripheral T lymphocytes. The transcriptome of thymocytes and peripheral CD3+ T lymphocytes from prediabetic or diabetic mice analyzed through microarray hybridizations identified 2,771 differentially expressed genes. Hierarchical clustering grouped mice according to age/T1D onset and genes according to their transcription profiling. The transcriptional activity of thymocytes developing into peripheral T lymphocytes revealed sequential participation of genes involved with CD4+/CD8+ T-cell differentiation (Themis), tolerance induction by Tregs (Foxp3), and apoptosis (Fasl) soon after T-cell activation (IL4), while the emergence of T1D coincided with the expression of cytotoxicity (Crtam) and inflammatory response genes (Tlr) by peripheral T lymphocytes. PMID:21765850

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.

Short-Range Temporal Interactions in Sleep; Hippocampal Spike Avalanches Support a Large Milieu of Sequential Activity Including Replay

PubMed Central

Mahoney, J. Matthew; Titiz, Ali S.; Hernan, Amanda E.; Scott, Rod C.

2016-01-01

Hippocampal neural systems consolidate multiple complex behaviors into memory. However, the temporal structure of neural firing supporting complex memory consolidation is unknown. Replay of hippocampal place cells during sleep supports the view that a simple repetitive behavior modifies sleep firing dynamics, but does not explain how multiple episodes could be integrated into associative networks for recollection during future cognition. Here we decode sequential firing structure within spike avalanches of all pyramidal cells recorded in sleeping rats after running in a circular track. We find that short sequences that combine into multiple long sequences capture the majority of the sequential structure during sleep, including replay of hippocampal place cells. The ensemble, however, is not optimized for maximally producing the behavior-enriched episode. Thus behavioral programming of sequential correlations occurs at the level of short-range interactions, not whole behavioral sequences and these short sequences are assembled into a large and complex milieu that could support complex memory consolidation. PMID:26866597

Ultrasensitive surveillance of sensors and processes

DOEpatents

Wegerich, Stephan W.; Jarman, Kristin K.; Gross, Kenneth C.

2001-01-01

A method and apparatus for monitoring a source of data for determining an operating state of a working system. The method includes determining a sensor (or source of data) arrangement associated with monitoring the source of data for a system, activating a method for performing a sequential probability ratio test if the data source includes a single data (sensor) source, activating a second method for performing a regression sequential possibility ratio testing procedure if the arrangement includes a pair of sensors (data sources) with signals which are linearly or non-linearly related; activating a third method for performing a bounded angle ratio test procedure if the sensor arrangement includes multiple sensors and utilizing at least one of the first, second and third methods to accumulate sensor signals and determining the operating state of the system.

Ultrasensitive surveillance of sensors and processes

DOEpatents

Wegerich, Stephan W.; Jarman, Kristin K.; Gross, Kenneth C.

1999-01-01

A method and apparatus for monitoring a source of data for determining an operating state of a working system. The method includes determining a sensor (or source of data) arrangement associated with monitoring the source of data for a system, activating a method for performing a sequential probability ratio test if the data source includes a single data (sensor) source, activating a second method for performing a regression sequential possibility ratio testing procedure if the arrangement includes a pair of sensors (data sources) with signals which are linearly or non-linearly related; activating a third method for performing a bounded angle ratio test procedure if the sensor arrangement includes multiple sensors and utilizing at least one of the first, second and third methods to accumulate sensor signals and determining the operating state of the system.

Cultural constraints on brain development: evidence from a developmental study of visual word processing in mandarin chinese.

PubMed

Cao, Fan; Lee, Rebecca; Shu, Hua; Yang, Yanhui; Xu, Guoqing; Li, Kuncheng; Booth, James R

2010-05-01

Developmental differences in phonological and orthographic processing in Chinese were examined in 9 year olds, 11 year olds, and adults using functional magnetic resonance imaging. Rhyming and spelling judgments were made to 2-character words presented sequentially in the visual modality. The spelling task showed greater activation than the rhyming task in right superior parietal lobule and right inferior temporal gyrus, and there were developmental increases across tasks bilaterally in these regions in addition to bilateral occipital cortex, suggesting increased involvement over age on visuo-orthographic analysis. The rhyming task showed greater activation than the spelling task in left superior temporal gyrus and there were developmental decreases across tasks in this region, suggesting reduced involvement over age on phonological representations. The rhyming and spelling tasks included words with conflicting orthographic and phonological information (i.e., rhyming words spelled differently or nonrhyming words spelled similarly) or nonconflicting information. There was a developmental increase in the difference between conflicting and nonconflicting words in left inferior parietal lobule, suggesting greater engagement of systems for mapping between orthographic and phonological representations. Finally, there were developmental increases across tasks in an anterior (Broadman area [BA] 45, 46) and posterior (BA 9) left inferior frontal gyrus, suggesting greater reliance on controlled retrieval and selection of posterior lexical representations.

SUMO proteases as potential targets for cancer therapy.

PubMed

Bialik, Piotr; Woźniak, Katarzyna

2017-12-08

Sumoylation is one of the post-translational modifications of proteins, responsible for the regulation of many cellular processes, such as DNA replication and repair, transcription, signal transduction and nuclear transport. During sumoylation, SUMO proteins are covalently attached to the ε-amino group of lysine in target proteins via an enzymatic cascade that requires the sequential action of E1, E2 and E3 enzymes. An important aspect of sumoylation is its reversibility, which involves SUMO-specific proteases called SENPs. SENPs (sentrin/SUMO-specific proteases) catalyze the deconjugation of SUMO proteins using their isopeptidase activity. These enzymes participate through hydrolase activity in the reaction of SUMO protein maturation, which involves the removal of a short fragment on the C-terminus of SUMO inactive form and exposure two glycine residues. SENPs are important for maintaining the balance between sumoylated and desumoylated proteins required for normal cellular physiology. Six SENP isoforms (SENP1, SENP2, SENP3, SENP5, SENP6 and SENP7) have been identified in mammals. These SENPs can be divided into three subfamilies based on their sequence homology, substrate specificity and subcellular localization. Results of studies indicate the role of SUMO proteases in the development of human diseases including cancer, suggesting that these proteins may be attractive targets for new drugs.

(Na+ + K+)-ATPase Is a Target for Phosphoinositide 3-Kinase/Protein Kinase B and Protein Kinase C Pathways Triggered by Albumin*

PubMed Central

Peruchetti, Diogo B.; Pinheiro, Ana Acacia S.; Landgraf, Sharon S.; Wengert, Mira; Takiya, Christina M.; Guggino, William B.; Caruso-Neves, Celso

2011-01-01

In recent decades, evidence has confirmed the crucial role of albumin in the progression of renal disease. However, the possible role of signaling pathways triggered by physiologic concentrations of albumin in the modulation of proximal tubule (PT) sodium reabsorption has not been considered. In the present work, we have shown that a physiologic concentration of albumin increases the expression of the α1 subunit of (Na+ + K+)-ATPase in LLC-PK1 cells leading to an increase in enzyme activity. This process involves the sequential activation of PI3K/protein kinase B and protein kinase C pathways promoting inhibition of protein kinase A. This integrative network is inhibited when albumin concentration is increased, similar to renal disease, leading to a decrease in the α1 subunit of (Na+ + K+)-ATPase expression. Together, the results indicate that variation in albumin concentration in PT cells has an important effect on PT sodium reabsorption and, consequently, on renal sodium excretion. PMID:22057272

Novel Acid Catalysts from Waste-Tire-Derived Carbon: Application in Waste-to-Biofuel Conversion

DOE PAGES

Hood, Zachary D.; Adhikari, Shiba P.; Li, Yunchao; ...

2017-06-21

Many inexpensive biofuel feedstocks, including those containing free fatty acids (FFAs) in high concentrations, are typically disposed of as waste due to our inability to efficiently convert them into usable biofuels. Here we demonstrate that carbon derived from waste tires could be functionalized with sulfonic acid (-SO 3H) to effectively catalyze the esterification of oleic acid or a mixture of fatty acids to usable biofuels. Waste tires were converted to hard carbon, then functionalized with catalytically active -SO 3H groups on the surface through an environmentally benign process that involved the sequential treatment with L-cysteine, dithiothreitol, and H 2O 2.more » In conclusion, when benchmarked against the same waste-tire derived carbon material treated with concentrated sulfuric acid at 150 °C, similar catalytic activity was observed. Both catalysts could also effectively convert oleic acid or a mixture of fatty acids and soybean oil to usable biofuels at 65 °C and 1 atm without leaching of the catalytic sites.« less

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

Hood, Zachary D.; Adhikari, Shiba P.; Li, Yunchao

Many inexpensive biofuel feedstocks, including those containing free fatty acids (FFAs) in high concentrations, are typically disposed of as waste due to our inability to efficiently convert them into usable biofuels. Here we demonstrate that carbon derived from waste tires could be functionalized with sulfonic acid (-SO 3H) to effectively catalyze the esterification of oleic acid or a mixture of fatty acids to usable biofuels. Waste tires were converted to hard carbon, then functionalized with catalytically active -SO 3H groups on the surface through an environmentally benign process that involved the sequential treatment with L-cysteine, dithiothreitol, and H 2O 2.more » In conclusion, when benchmarked against the same waste-tire derived carbon material treated with concentrated sulfuric acid at 150 °C, similar catalytic activity was observed. Both catalysts could also effectively convert oleic acid or a mixture of fatty acids and soybean oil to usable biofuels at 65 °C and 1 atm without leaching of the catalytic sites.« less

Decision making and action implementation: evidence for an early visually triggered motor activation specific to potential actions.

PubMed

Tandonnet, Christophe; Garry, Michael I; Summers, Jeffery J

2013-07-01

To make a decision may rely on accumulating evidence in favor of one alternative until a threshold is reached. Sequential-sampling models differ by the way of accumulating evidence and the link with action implementation. Here, we tested a model's prediction of an early action implementation specific to potential actions. We assessed the dynamics of action implementation in go/no-go and between-hand choice tasks by transcranial magnetic stimulation of the motor cortex (single- or paired-pulse TMS; 3-ms interstimulus interval). Prior to implementation of the selected action, the amplitude of the motor evoked potential first increased whatever the visual stimulus but only for the hand potentially involved in the to-be-produced action. These findings suggest that visual stimuli can trigger an early motor activation specific to potential actions, consistent with race-like models with continuous transmission between decision making and action implementation. Copyright © 2013 Society for Psychophysiological Research.

New Molecular Bridge between RelA/p65 and NF-κB Target Genes via Histone Acetyltransferase TIP60 Cofactor*

PubMed Central

Kim, Jung-Woong; Jang, Sang-Min; Kim, Chul-Hong; An, Joo-Hee; Kang, Eun-Jin; Choi, Kyung-Hee

2012-01-01

The nuclear factor-κB (NF-κB) family is involved in the expressions of numerous genes, in development, apoptosis, inflammatory responses, and oncogenesis. In this study we identified four NF-κB target genes that are modulated by TIP60. We also found that TIP60 interacts with the NF-κB RelA/p65 subunit and increases its transcriptional activity through protein-protein interaction. Although TIP60 binds with RelA/p65 using its histone acetyltransferase domain, TIP60 does not directly acetylate RelA/p65. However, TIP60 maintained acetylated Lys-310 RelA/p65 levels in the TNF-α-dependent NF-κB signaling pathway. In chromatin immunoprecipitation assay, TIP60 was primarily recruited to the IL-6, IL-8, C-IAP1, and XIAP promoters in TNF-α stimulation followed by acetylation of histones H3 and H4. Chromatin remodeling by TIP60 involved the sequential recruitment of acetyl-Lys-310 RelA/p65 to its target gene promoters. Furthermore, we showed that up-regulated TIP60 expression was correlated with acetyl-Lys-310 RelA/p65 expressions in hepatocarcinoma tissues. Taken together these results suggest that TIP60 is involved in the NF-κB pathway through protein interaction with RelA/p65 and that it modulates the transcriptional activity of RelA/p65 in NF-κB-dependent gene expression. PMID:22249179

Sea Fighter Analysis

DTIC Science & Technology

2007-02-01

which is used by the model to drive the normal activities of the crew (Figure C.1-2). These routines consist of a sequential list of high- level...separately. Figure C.1-3: Resources & Logic Sheet C.1.1.4 Scenario The scenario that is performed during a model run is a sequential list of all...were marked with a white fore and aft lineup stripe on both landing spots. Current Sea Fighter design does not provide a hangar; however, there

Near real-time adverse drug reaction surveillance within population-based health networks: methodology considerations for data accrual.

PubMed

Avery, Taliser R; Kulldorff, Martin; Vilk, Yury; Li, Lingling; Cheetham, T Craig; Dublin, Sascha; Davis, Robert L; Liu, Liyan; Herrinton, Lisa; Brown, Jeffrey S

2013-05-01

This study describes practical considerations for implementation of near real-time medical product safety surveillance in a distributed health data network. We conducted pilot active safety surveillance comparing generic divalproex sodium to historical branded product at four health plans from April to October 2009. Outcomes reported are all-cause emergency room visits and fractures. One retrospective data extract was completed (January 2002-June 2008), followed by seven prospective monthly extracts (January 2008-November 2009). To evaluate delays in claims processing, we used three analytic approaches: near real-time sequential analysis, sequential analysis with 1.5 month delay, and nonsequential (using final retrospective data). Sequential analyses used the maximized sequential probability ratio test. Procedural and logistical barriers to active surveillance were documented. We identified 6586 new users of generic divalproex sodium and 43,960 new users of the branded product. Quality control methods identified 16 extract errors, which were corrected. Near real-time extracts captured 87.5% of emergency room visits and 50.0% of fractures, which improved to 98.3% and 68.7% respectively with 1.5 month delay. We did not identify signals for either outcome regardless of extract timeframe, and slight differences in the test statistic and relative risk estimates were found. Near real-time sequential safety surveillance is feasible, but several barriers warrant attention. Data quality review of each data extract was necessary. Although signal detection was not affected by delay in analysis, when using a historical control group differential accrual between exposure and outcomes may theoretically bias near real-time risk estimates towards the null, causing failure to detect a signal. Copyright © 2013 John Wiley & Sons, Ltd.

Alternating sequential chemotherapy with high-dose ifosfamide and doxorubicin/cyclophosphamide for adult non-small round cell soft tissue sarcomas.

PubMed

Kawai, Akira; Umeda, Toru; Wada, Takuro; Ihara, Koichiro; Isu, Kazuo; Abe, Satoshi; Ishii, Takeshi; Sugiura, Hideshi; Araki, Nobuhito; Ozaki, Toshifumi; Yabe, Hiroo; Hasegawa, Tadashi; Tsugane, Shoichiro; Beppu, Yasuo

2005-05-01

Doxorubicin and ifosfamide are the two most active agents used to treat soft tissue sarcomas. However, because of their overlapping side effects, concurrent administration to achieve optimal doses of each agent is difficult. We therefore conducted a Phase II trial to investigate the efficacy and feasibility of a novel alternating sequential chemotherapy regimen consisting of high dose ifosfamide and doxorubicin/cyclophosphamide in advanced adult non-small round cell soft tissue sarcomas. Adult patients with non-small round cell soft tissue sarcomas were enrolled. The treatment consisted of four sequential courses of chemotherapy that was planned for every 3 weeks. Cycles 1 and 3 consisted of ifosfamide (14 g/m(2)), and cycles 2 and 4 consisted of doxorubicin (60 mg/m(2)) and cyclophosphamide (1200 mg/m(2)). Forty-two patients (median age 47 years) were enrolled. Of the 36 assessable patients, 1 complete response and 16 partial responses were observed, for a response rate of 47.2%. Responses were observed in 57% of patients who had received no previous chemotherapy and 13% of those who had previously undergone chemotherapy. Grade 3-4 neutropenia was observed during 70% of all cycles. Sequential administration of high-dose ifosfamide and doxorubicin/cyclophosphamide has promising activity with manageable side effects in patients with advanced adult non-small round cell soft tissue sarcomas.

Reaction Intermediates of Quinol Oxidation in a Photoactivatable System that Mimics Electron Transfer in the Cytochrome bc1 Complex

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

Cape, Jonathan L.; Bowman, Michael K.; Kramer, David M.

2005-03-30

Current competing models for the two-electron oxidation of quinol (QH{sub 2}) at the cytochrome bc{sub 1} complex and related complexes have different requirements for the reaction intermediate. At present, the intermediate species of the enzymatic oxidation process have not been observed or characterized, probably due to their transient nature. Here, we use a biomimetic oxidant, Ru(bpy){sub 2}(pbim)(PF6)2 (bpy = 2,2'-dipyridyl, pbim = 2-(2-benzimidazolate)pyridine) in an aprotic medium to probe the oxidation of the ubiquinol analogue, 2,3-dimethoxy-5-methyl-1,4-benzoquinol (UQH{sub 2}-0), an the plastoquinol analogue, trimethyl-1,4-benzoquinol (TMQH{sub 2}-0), using time-resolved and steady state spectroscopic techniques. This system qualitatively reproduces key features observed duringmore » ubiquinol oxidation by the mitochondrial cytochrome bc1 complex. Comparison of isotope dependent activation properties in the native and synthetic systems, as well as, analysis of the time-resolved direct-detection electron para magnetic resonance signals in the synthetic system allows us to conclude that: (1) the initial and rate-limiting step in quinol oxidation, both in the biological and biomimetic systems, involves electron and proton transfer, probably via a proton coupled electron transfer mechanism; (2) a neutral semiquinone intermediate is formed in the biomimetic system; and (3) oxidation of the QH*/QH{sub 2} couple for UQH{sub 2}-0, but not TMQH{sub 2}-0, exhibits a non-classical primary deuterium kinetic isotope effect on its Arrhenius activation energy ({Delta}G{sup TS}), where {Delta}G{sup TS} for the protiated form is larger than for the deuterated form. The same behavior is observed during steady state turnover of the cyt bc{sub 1} complex using ubiquinol, but not plastoquinol, as a substrate, leading to the conclusion that similar chemical pathways are involved in both systems. The synthetic system is an unambiguous n=1 electron acceptor and it is thus inferred that sequential oxidation of ubiquinol (by two sequential n=1 processes) is more rapid than a truly concerted (n=2) oxidation in the cyt bc{sub 1} complex.« less

Simultaneous activation of parallel sensory pathways promotes a grooming sequence in Drosophila

PubMed Central

Hampel, Stefanie; McKellar, Claire E

2017-01-01

A central model that describes how behavioral sequences are produced features a neural architecture that readies different movements simultaneously, and a mechanism where prioritized suppression between the movements determines their sequential performance. We previously described a model whereby suppression drives a Drosophila grooming sequence that is induced by simultaneous activation of different sensory pathways that each elicit a distinct movement (Seeds et al., 2014). Here, we confirm this model using transgenic expression to identify and optogenetically activate sensory neurons that elicit specific grooming movements. Simultaneous activation of different sensory pathways elicits a grooming sequence that resembles the naturally induced sequence. Moreover, the sequence proceeds after the sensory excitation is terminated, indicating that a persistent trace of this excitation induces the next grooming movement once the previous one is performed. This reveals a mechanism whereby parallel sensory inputs can be integrated and stored to elicit a delayed and sequential grooming response. PMID:28887878

Transfer-printing of active layers to achieve high quality interfaces in sequentially deposited multilayer inverted polymer solar cells fabricated in air

PubMed Central

Vohra, Varun; Anzai, Takuya; Inaba, Shusei; Porzio, William; Barba, Luisa

2016-01-01

Abstract Polymer solar cells (PSCs) are greatly influenced by both the vertical concentration gradient in the active layer and the quality of the various interfaces. To achieve vertical concentration gradients in inverted PSCs, a sequential deposition approach is necessary. However, a direct approach to sequential deposition by spin-coating results in partial dissolution of the underlying layers which decreases the control over the process and results in not well-defined interfaces. Here, we demonstrate that by using a transfer-printing process based on polydimethylsiloxane (PDMS) stamps we can obtain increased control over the thickness of the various layers while at the same time increasing the quality of the interfaces and the overall concentration gradient within the active layer of PSCs prepared in air. To optimize the process and understand the influence of various interlayers, our approach is based on surface free energy, spreading parameters and work of adhesion calculations. The key parameter presented here is the insertion of high quality hole transporting and electron transporting layers, respectively above and underneath the active layer of the inverted structure PSC which not only facilitates the transfer process but also induces the adequate vertical concentration gradient in the device to facilitate charge extraction. The resulting non-encapsulated devices (active layer prepared in air) demonstrate over 40% increase in power conversion efficiency with respect to the reference spin-coated inverted PSCs. PMID:27877901

Multimodal sensory integration during sequential eating--linking chewing activity, aroma release, and aroma perception over time.

PubMed

Leclercq, Ségolène; Blancher, Guillaume

2012-10-01

The respective effects of chewing activity, aroma release from a gelled candy, and aroma perception were investigated. Specifically, the study aimed at 1) comparing an imposed chewing and swallowing pattern (IP) and free protocol (FP) on panelists for in vivo measurements, 2) investigating carryover effects in sequential eating, and 3) studying the link between instrumental data and their perception counterpart. Chewing activity, in-nose aroma concentration, and aroma perception over time were measured by electromyography, proton transfer reaction-mass spectrometry, and time intensity, respectively. Model gel candies were flavored at 2 intensity levels (low-L and high-H). The panelists evaluated 3 sequences (H then H, H then L, and L then H) in duplicates with both IP and FP. They scored aroma intensity over time while their in-nose aroma concentrations and their chewing activity were measured. Overall, only limited advantages were found in imposing a chewing and swallowing pattern for instrumental and sensory data. In addition, the study highlighted the role of brain integration on perceived intensity and dynamics of perception, in the framework of sequential eating without rinsing. Because of the presence of adaptation phenomena, contrast effect, and potential taste and texture cross-modal interaction with aroma perception, it was concluded that dynamic in-nose concentration data provide only one part of the perception picture and therefore cannot be used alone in prediction models.

Different propagation speeds of recalled sequences in plastic spiking neural networks

NASA Astrophysics Data System (ADS)

Huang, Xuhui; Zheng, Zhigang; Hu, Gang; Wu, Si; Rasch, Malte J.

2015-03-01

Neural networks can generate spatiotemporal patterns of spike activity. Sequential activity learning and retrieval have been observed in many brain areas, and e.g. is crucial for coding of episodic memory in the hippocampus or generating temporal patterns during song production in birds. In a recent study, a sequential activity pattern was directly entrained onto the neural activity of the primary visual cortex (V1) of rats and subsequently successfully recalled by a local and transient trigger. It was observed that the speed of activity propagation in coordinates of the retinotopically organized neural tissue was constant during retrieval regardless how the speed of light stimulation sweeping across the visual field during training was varied. It is well known that spike-timing dependent plasticity (STDP) is a potential mechanism for embedding temporal sequences into neural network activity. How training and retrieval speeds relate to each other and how network and learning parameters influence retrieval speeds, however, is not well described. We here theoretically analyze sequential activity learning and retrieval in a recurrent neural network with realistic synaptic short-term dynamics and STDP. Testing multiple STDP rules, we confirm that sequence learning can be achieved by STDP. However, we found that a multiplicative nearest-neighbor (NN) weight update rule generated weight distributions and recall activities that best matched the experiments in V1. Using network simulations and mean-field analysis, we further investigated the learning mechanisms and the influence of network parameters on recall speeds. Our analysis suggests that a multiplicative STDP rule with dominant NN spike interaction might be implemented in V1 since recall speed was almost constant in an NMDA-dominant regime. Interestingly, in an AMPA-dominant regime, neural circuits might exhibit recall speeds that instead follow the change in stimulus speeds. This prediction could be tested in experiments.

Sequential sampling: a novel method in farm animal welfare assessment.

PubMed

Heath, C A E; Main, D C J; Mullan, S; Haskell, M J; Browne, W J

2016-02-01

Lameness in dairy cows is an important welfare issue. As part of a welfare assessment, herd level lameness prevalence can be estimated from scoring a sample of animals, where higher levels of accuracy are associated with larger sample sizes. As the financial cost is related to the number of cows sampled, smaller samples are preferred. Sequential sampling schemes have been used for informing decision making in clinical trials. Sequential sampling involves taking samples in stages, where sampling can stop early depending on the estimated lameness prevalence. When welfare assessment is used for a pass/fail decision, a similar approach could be applied to reduce the overall sample size. The sampling schemes proposed here apply the principles of sequential sampling within a diagnostic testing framework. This study develops three sequential sampling schemes of increasing complexity to classify 80 fully assessed UK dairy farms, each with known lameness prevalence. Using the Welfare Quality herd-size-based sampling scheme, the first 'basic' scheme involves two sampling events. At the first sampling event half the Welfare Quality sample size is drawn, and then depending on the outcome, sampling either stops or is continued and the same number of animals is sampled again. In the second 'cautious' scheme, an adaptation is made to ensure that correctly classifying a farm as 'bad' is done with greater certainty. The third scheme is the only scheme to go beyond lameness as a binary measure and investigates the potential for increasing accuracy by incorporating the number of severely lame cows into the decision. The three schemes are evaluated with respect to accuracy and average sample size by running 100 000 simulations for each scheme, and a comparison is made with the fixed size Welfare Quality herd-size-based sampling scheme. All three schemes performed almost as well as the fixed size scheme but with much smaller average sample sizes. For the third scheme, an overall association between lameness prevalence and the proportion of lame cows that were severely lame on a farm was found. However, as this association was found to not be consistent across all farms, the sampling scheme did not prove to be as useful as expected. The preferred scheme was therefore the 'cautious' scheme for which a sampling protocol has also been developed.

Online Graph Completion: Multivariate Signal Recovery in Computer Vision.

PubMed

Kim, Won Hwa; Jalal, Mona; Hwang, Seongjae; Johnson, Sterling C; Singh, Vikas

2017-07-01

The adoption of "human-in-the-loop" paradigms in computer vision and machine learning is leading to various applications where the actual data acquisition (e.g., human supervision) and the underlying inference algorithms are closely interwined. While classical work in active learning provides effective solutions when the learning module involves classification and regression tasks, many practical issues such as partially observed measurements, financial constraints and even additional distributional or structural aspects of the data typically fall outside the scope of this treatment. For instance, with sequential acquisition of partial measurements of data that manifest as a matrix (or tensor), novel strategies for completion (or collaborative filtering) of the remaining entries have only been studied recently. Motivated by vision problems where we seek to annotate a large dataset of images via a crowdsourced platform or alternatively, complement results from a state-of-the-art object detector using human feedback, we study the "completion" problem defined on graphs, where requests for additional measurements must be made sequentially. We design the optimization model in the Fourier domain of the graph describing how ideas based on adaptive submodularity provide algorithms that work well in practice. On a large set of images collected from Imgur, we see promising results on images that are otherwise difficult to categorize. We also show applications to an experimental design problem in neuroimaging.

Atypical cleavage of protonated N-fatty acyl amino acids derived from aspartic acid evidenced by sequential MS3 experiments.

PubMed

Boukerche, Toufik Taalibi; Alves, Sandra; Le Faouder, Pauline; Warnet, Anna; Bertrand-Michel, Justine; Bouchekara, Mohamed; Belbachir, Mohammed; Tabet, Jean-Claude

2016-12-01

Lipidomics calls for information on detected lipids and conjugates whose structural elucidation by mass spectrometry requires to rationalization of their gas phase dissociations toward collision-induced dissociation (CID) processes. This study focused on activated dissociations of two lipoamino acid (LAA) systems composed of N-palmitoyl acyl coupled with aspartic and glutamic acid mono ethyl esters (as LAA (*D) and LAA (*E) ). Although in MS/MS, their CID spectra show similar trends, e.g., release of water and ethanol, the [(LAA (*D/*E) +H)-C 2 H 5 OH] + product ions dissociate via distinct pathways in sequential MS 3 experiments. The formation of all the product ions is rationalized by charge-promoted cleavages often involving stepwise processes with ion isomerization into ion-dipole prior to dissociation. The latter explains the maleic anhydride or ketene neutral losses from N-palmitoyl acyl aspartate and glutamate anhydride fragment ions, respectively. Consequently, protonated palmitoyl acid amide is generated from LAA (*D), whereas LAA (*E) leads to the [*E+H-H 2 O] + anhydride. The former releases ammonia to provide acylium, which gives the C n H (2n-1) and C n H (2n-3) carbenium series. This should offer structural information, e.g., to locate either unsaturation(s) or alkyl group branching present on the various fatty acyl moieties of lipo-aspartic acid in further studies based on MS n experiments.

Bilateral Non-arteritic Anterior Ischaemic Optic Neuropathy as the Presentation of Systemic Amyloidosis.

PubMed

Kanaan, M Z; Lorenzi, A R; Thampy, N; Pandit, R; Dayan, Margaret

2017-12-01

A 75-year-old hypertensive female with stable idiopathic intermediate uveitis presented with bilateral sequential optic neuropathy with optic disc swelling. The optic neuropathy in the first affected eye (right) was thought to be due to non-arteritic anterior ischaemic optic neuropathy (NAION). Asymptomatic left optic disc swelling was found at routine review 2 months later, and a diagnosis of giant cell arteritis (GCA) was sought. Temporal artery duplex ultrasound showed the "halo sign," but a subsequent temporal artery biopsy showed light-chain (AL) amyloidosis with no signs of giant cell arteritis. In this case, bilateral sequential ischaemic optic neuropathy mimicking non-arteritic anterior ischaemic optic neuropathy was the presenting sign of systemic amyloidosis involving the temporal arteries.

Rate-dependent inverse-addition beta-selective mannosylation and contiguous sequential glycosylation involving beta-mannosidic bond formation.

PubMed

Chang, Shih-Sheng; Shih, Che-Hao; Lai, Kwun-Cheng; Mong, Kwok-Kong Tony

2010-05-03

The beta-selectivity of mannosylation has been found to be dependent on the addition rate of the mannosyl trichloroacetimidate donor in an inverse-addition (I-A) procedure. This rate dependent I-A procedure can improve the selectivity of direct beta-mannosylation and is applicable to orthogonal glycosylations of thioglycoside acceptors. Further elaboration of this novel procedure enables the development of the contiguous sequential glycosylation strategy, which streamlines the preparation of oligosaccharides invoking beta-mannosidic bond formation. The synthetic utility of the contiguous glycosylation strategy was demonstrated by the preparation of the trisaccharide core of human N-linked glycoproteins and the trisaccharide repeating unit of the O-specific polysaccharide found in the cellular capsule of Salmonelle bacteria.

Sequential anaerobic-aerobic degradation of munitions waste.

PubMed

Ibeanusi, Victor; Jeilani, Yassin; Houston, Samantha; Doss, Danielle; Coley, Bianca

2009-01-01

A sequential anaerobic-aerobic biodegradation of hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) was studied. The results demonstrated that: (i) a complete degradation of RDX was achieved within 20 days using a consortium of bacteria from a wastewater activated sludge, (ii) RDX degradation did not occur under aerobic conditions alone, (iii) RDX-degrading bacterial strain that was isolated from the activated sludge completely degraded RDX within 2 days, and (iv) RDX- induced protein expressions were observed in the RDX-degrading bacterial strain. Based on fatty acid composition and a confirmation with a 16S rRNA analysis, the RDX-degrading bacterial strain was identified as a Bacillus pumilus-GC subgroup B.

Cortical Plasticity after Cochlear Implantation

PubMed Central

Petersen, B.; Gjedde, A.; Wallentin, M.; Vuust, P.

2013-01-01

The most dramatic progress in the restoration of hearing takes place in the first months after cochlear implantation. To map the brain activity underlying this process, we used positron emission tomography at three time points: within 14 days, three months, and six months after switch-on. Fifteen recently implanted adult implant recipients listened to running speech or speech-like noise in four sequential PET sessions at each milestone. CI listeners with postlingual hearing loss showed differential activation of left superior temporal gyrus during speech and speech-like stimuli, unlike CI listeners with prelingual hearing loss. Furthermore, Broca's area was activated as an effect of time, but only in CI listeners with postlingual hearing loss. The study demonstrates that adaptation to the cochlear implant is highly related to the history of hearing loss. Speech processing in patients whose hearing loss occurred after the acquisition of language involves brain areas associated with speech comprehension, which is not the case for patients whose hearing loss occurred before the acquisition of language. Finally, the findings confirm the key role of Broca's area in restoration of speech perception, but only in individuals in whom Broca's area has been active prior to the loss of hearing. PMID:24377050

Hydrogen production by the naked active site of the di-iron hydrogenases in water.

PubMed

Zipoli, Federico; Car, Roberto; Cohen, Morrel H; Selloni, Annabella

2009-10-01

We explored the reactivity of the active center of the [FeFe]-hydrogenases detached from the enzyme and immersed in acidified water by first-principles Car-Parrinello molecular-dynamics simulations. We focused on the identification of the structures that are stable and metastable in acidified water and on their activity for hydrogen production. Our calculations revealed that the naked active center could be an efficient catalyst provided that electrons are transferred to the cluster. We found that both bridging and terminal isomers are present at equilibrium and that the bridging configuration is essential for efficient hydrogen production. The formation of the hydrogen molecule occurs via sequential protonations of the distal iron and of the N-atom of the S-CH(2)-NH-CH(2)-S chelating group. H(2) desorption does not involve a significant energy barrier, making the process very efficient at room temperature. We established that the bottleneck in the reaction is the direct proton transfer from water to the vacant site of the distal iron. Moreover, we found that even if the terminal isomer is present at the equilibrium, its strong local hydrophobicity prevents poisoning of the cluster.

A G-quadruplex-binding macrodomain within the "SARS-unique domain" is essential for the activity of the SARS-coronavirus replication-transcription complex.

PubMed

Kusov, Yuri; Tan, Jinzhi; Alvarez, Enrique; Enjuanes, Luis; Hilgenfeld, Rolf

2015-10-01

The multi-domain non-structural protein 3 of SARS-coronavirus is a component of the viral replication/transcription complex (RTC). Among other domains, it contains three sequentially arranged macrodomains: the X domain and subdomains SUD-N as well as SUD-M within the "SARS-unique domain". The X domain was proposed to be an ADP-ribose-1"-phosphatase or a poly(ADP-ribose)-binding protein, whereas SUD-NM binds oligo(G)-nucleotides capable of forming G-quadruplexes. Here, we describe the application of a reverse genetic approach to assess the importance of these macrodomains for the activity of the SARS-CoV RTC. To this end, Renilla luciferase-encoding SARS-CoV replicons with selectively deleted macrodomains were constructed and their ability to modulate the RTC activity was examined. While the SUD-N and the X domains were found to be dispensable, the SUD-M domain was crucial for viral genome replication/transcription. Moreover, alanine replacement of charged amino-acid residues of the SUD-M domain, which are likely involved in G-quadruplex-binding, caused abrogation of RTC activity. Copyright © 2015 Elsevier Inc. All rights reserved.

Decision making and sequential sampling from memory

PubMed Central

Shadlen, Michael N.; Shohamy, Daphna

2016-01-01

Decisions take time, and as a rule more difficult decisions take more time. But this only raises the question of what consumes the time. For decisions informed by a sequence of samples of evidence, the answer is straightforward: more samples are available with more time. Indeed the speed and accuracy of such decisions are explained by the accumulation of evidence to a threshold or bound. However, the same framework seems to apply to decisions that are not obviously informed by sequences of evidence samples. Here we proffer the hypothesis that the sequential character of such tasks involves retrieval of evidence from memory. We explore this hypothesis by focusing on value-based decisions and argue that mnemonic processes can account for regularities in choice and decision time. We speculate on the neural mechanisms that link sampling of evidence from memory to circuits that represent the accumulated evidence bearing on a choice. We propose that memory processes may contribute to a wider class of decisions that conform to the regularities of choice-reaction time predicted by the sequential sampling framework. PMID:27253447

Sequential and ordered assembly of a large DNA repair complex on undamaged chromatin

PubMed Central

Ziani, Salim; Nagy, Zita; Alekseev, Sergey; Soutoglou, Evi; Egly, Jean-Marc

2014-01-01

In nucleotide excision repair (NER), damage recognition by XPC-hHR23b is described as a critical step in the formation of the preincision complex (PInC) further composed of TFIIH, XPA, RPA, XPG, and ERCC1-XPF. To obtain new molecular insights into the assembly of the PInC, we analyzed its formation independently of DNA damage by using the lactose operator/repressor reporter system. We observed a sequential and ordered self-assembly of the PInC operating upon immobilization of individual NER factors on undamaged chromatin and mimicking that functioning on a bona fide NER substrate. We also revealed that the recruitment of the TFIIH subunit TTDA, involved in trichothiodystrophy group A disorder (TTD-A), was key in the completion of the PInC. TTDA recruits XPA through its first 15 amino acids, depleted in some TTD-A patients. More generally, these results show that proteins forming large nuclear complexes can be recruited sequentially on chromatin in the absence of their natural DNA target and with no reciprocity in their recruitment. PMID:25154395

Bridging the qualitative-quantitative divide: Experiences from conducting a mixed methods evaluation in the RUCAS programme.

PubMed

Makrakis, Vassilios; Kostoulas-Makrakis, Nelly

2016-02-01

Quantitative and qualitative approaches to planning and evaluation in education for sustainable development have often been treated by practitioners from a single research paradigm. This paper discusses the utility of mixed method evaluation designs which integrate qualitative and quantitative data through a sequential transformative process. Sequential mixed method data collection strategies involve collecting data in an iterative process whereby data collected in one phase contribute to data collected in the next. This is done through examples from a programme addressing the 'Reorientation of University Curricula to Address Sustainability (RUCAS): A European Commission Tempus-funded Programme'. It is argued that the two approaches are complementary and that there are significant gains from combining both. Using methods from both research paradigms does not, however, mean that the inherent differences among epistemologies and methodologies should be neglected. Based on this experience, it is recommended that using a sequential transformative mixed method evaluation can produce more robust results than could be accomplished using a single approach in programme planning and evaluation focussed on education for sustainable development. Copyright © 2015 Elsevier Ltd. All rights reserved.

In-situ sequential laser transfer and laser reduction of graphene oxide films

NASA Astrophysics Data System (ADS)

Papazoglou, S.; Petridis, C.; Kymakis, E.; Kennou, S.; Raptis, Y. S.; Chatzandroulis, S.; Zergioti, I.

2018-04-01

Achieving high quality transfer of graphene on selected substrates is a priority in device fabrication, especially where drop-on-demand applications are involved. In this work, we report an in-situ, fast, simple, and one step process that resulted in the reduction, transfer, and fabrication of reduced graphene oxide-based humidity sensors, using picosecond laser pulses. By tuning the laser illumination parameters, we managed to implement the sequential printing and reduction of graphene oxide flakes. The overall process lasted only a few seconds compared to a few hours that our group has previously published. DC current measurements, X-Ray Photoelectron Spectroscopy, X-Ray Diffraction, and Raman Spectroscopy were employed in order to assess the efficiency of our approach. To demonstrate the applicability and the potential of the technique, laser printed reduced graphene oxide humidity sensors with a limit of detection of 1700 ppm are presented. The results demonstrated in this work provide a selective, rapid, and low-cost approach for sequential transfer and photochemical reduction of graphene oxide micro-patterns onto various substrates for flexible electronics and sensor applications.

Development of brain networks involved in spoken word processing of Mandarin Chinese.

PubMed

Cao, Fan; Khalid, Kainat; Lee, Rebecca; Brennan, Christine; Yang, Yanhui; Li, Kuncheng; Bolger, Donald J; Booth, James R

2011-08-01

Developmental differences in phonological and orthographic processing of Chinese spoken words were examined in 9-year-olds, 11-year-olds and adults using functional magnetic resonance imaging (fMRI). Rhyming and spelling judgments were made to two-character words presented sequentially in the auditory modality. Developmental comparisons between adults and both groups of children combined showed that age-related changes in activation in visuo-orthographic regions depended on a task. There were developmental increases in the left inferior temporal gyrus and the right inferior occipital gyrus in the spelling task, suggesting more extensive visuo-orthographic processing in a task that required access to these representations. Conversely, there were developmental decreases in activation in the left fusiform gyrus and left middle occipital gyrus in the rhyming task, suggesting that the development of reading is marked by reduced involvement of orthography in a spoken language task that does not require access to these orthographic representations. Developmental decreases may arise from the existence of extensive homophony (auditory words that have multiple spellings) in Chinese. In addition, we found that 11-year-olds and adults showed similar activation in the left superior temporal gyrus across tasks, with both groups showing greater activation than 9-year-olds. This pattern suggests early development of perceptual representations of phonology. In contrast, 11-year-olds and 9-year-olds showed similar activation in the left inferior frontal gyrus across tasks, with both groups showing weaker activation than adults. This pattern suggests late development of controlled retrieval and selection of lexical representations. Altogether, this study suggests differential effects of character acquisition on development of components of the language network in Chinese as compared to previous reports on alphabetic languages. Published by Elsevier Inc.

Calcium signaling in brain mitochondria: interplay of malate aspartate NADH shuttle and calcium uniporter/mitochondrial dehydrogenase pathways.

PubMed

Contreras, Laura; Satrústegui, Jorgina

2009-03-13

Ca2+ signaling in mitochondria has been mainly attributed to Ca2+ entry to the matrix through the Ca2+ uniporter and activation of mitochondrial matrix dehydrogenases. However, mitochondria can also sense increases in cytosolic Ca2+ through a mechanism that involves the aspartate-glutamate carriers, extramitochondrial Ca2+ activation of the NADH malate-aspartate shuttle (MAS). Both pathways are linked through the shared substrate alpha-ketoglutarate (alphaKG). Here we have studied the interplay between the two pathways under conditions of Ca2+ activation. We show that alphaKG becomes limiting when Ca2+ enters in brain or heart mitochondria, but not liver mitochondria, resulting in a drop in alphaKG efflux through the oxoglutarate carrier and in a drop in MAS activity. Inhibition of alphaKG efflux and MAS activity by matrix Ca2+ in brain mitochondria was fully reversible upon Ca2+ efflux. Because of their differences in cytosolic calcium concentration requirements, the MAS and Ca2+ uniporter-mitochondrial dehydrogenase pathways are probably sequentially activated during a Ca2+ transient, and the inhibition of MAS at the center of the transient may provide an explanation for part of the increase in lactate observed in the stimulated brain in vivo.

Preparation and characterization of cobalt-substituted anthrax lethal factor

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

Saebel, Crystal E.; Carbone, Ryan; Dabous, John R.

2011-12-09

Highlights: Black-Right-Pointing-Pointer Cobalt-substituted anthrax lethal factor (CoLF) is highly active. Black-Right-Pointing-Pointer CoLF can be prepared by bio-assimilation and direct exchange. Black-Right-Pointing-Pointer Lethal factor binds cobalt tightly. Black-Right-Pointing-Pointer The electronic spectrum of CoLF reveals penta-coordination. Black-Right-Pointing-Pointer Interaction of CoLF with thioglycolic acid follows a 2-step mechanism. -- Abstract: Anthrax lethal factor (LF) is a zinc-dependent endopeptidase involved in the cleavage of mitogen-activated protein kinase kinases near their N-termini. The current report concerns the preparation of cobalt-substituted LF (CoLF) and its characterization by electronic spectroscopy. Two strategies to produce CoLF were explored, including (i) a bio-assimilation approach involving the cultivation of LF-expressingmore » Bacillus megaterium cells in the presence of CoCl{sub 2}, and (ii) direct exchange by treatment of zinc-LF with CoCl{sub 2}. Independent of the method employed, the protein was found to contain one Co{sup 2+} per LF molecule, and was shown to be twice as active as its native zinc counterpart. The electronic spectrum of CoLF suggests the Co{sup 2+} ion to be five-coordinate, an observation similar to that reported for other Co{sup 2+}-substituted gluzincins, but distinct from that documented for the crystal structure of native LF. Furthermore, spectroscopic studies following the exposure of CoLF to thioglycolic acid (TGA) revealed a sequential mechanism of metal removal from LF, which likely involves the formation of an enzyme: Co{sup 2+}:TGA ternary complex prior to demetallation of the active site. CoLF reported herein constitutes the first spectroscopic probe of LF's active site, which may be utilized in future studies to gain further insight into the enzyme's mechanism and inhibitor interactions.« less

The neural basis of responsibility attribution in decision-making.

PubMed

Li, Peng; Shen, Yue; Sui, Xue; Chen, Changming; Feng, Tingyong; Li, Hong; Holroyd, Clay

2013-01-01

Social responsibility links personal behavior with societal expectations and plays a key role in affecting an agent's emotional state following a decision. However, the neural basis of responsibility attribution remains unclear. In two previous event-related brain potential (ERP) studies we found that personal responsibility modulated outcome evaluation in gambling tasks. Here we conducted a functional magnetic resonance imaging (fMRI) study to identify particular brain regions that mediate responsibility attribution. In a context involving team cooperation, participants completed a task with their teammates and on each trial received feedback about team success and individual success sequentially. We found that brain activity differed between conditions involving team success vs. team failure. Further, different brain regions were associated with reinforcement of behavior by social praise vs. monetary reward. Specifically, right temporoparietal junction (RTPJ) was associated with social pride whereas dorsal striatum and dorsal anterior cingulate cortex (ACC) were related to reinforcement of behaviors leading to personal gain. The present study provides evidence that the RTPJ is an important region for determining whether self-generated behaviors are deserving of praise in a social context.

The Neural Basis of Responsibility Attribution in Decision-Making

PubMed Central

Li, Peng; Shen, Yue; Sui, Xue; Chen, Changming; Feng, Tingyong; Li, Hong; Holroyd, Clay

2013-01-01

Social responsibility links personal behavior with societal expectations and plays a key role in affecting an agent’s emotional state following a decision. However, the neural basis of responsibility attribution remains unclear. In two previous event-related brain potential (ERP) studies we found that personal responsibility modulated outcome evaluation in gambling tasks. Here we conducted a functional magnetic resonance imaging (fMRI) study to identify particular brain regions that mediate responsibility attribution. In a context involving team cooperation, participants completed a task with their teammates and on each trial received feedback about team success and individual success sequentially. We found that brain activity differed between conditions involving team success vs. team failure. Further, different brain regions were associated with reinforcement of behavior by social praise vs. monetary reward. Specifically, right temporoparietal junction (RTPJ) was associated with social pride whereas dorsal striatum and dorsal anterior cingulate cortex (ACC) were related to reinforcement of behaviors leading to personal gain. The present study provides evidence that the RTPJ is an important region for determining whether self-generated behaviors are deserving of praise in a social context. PMID:24224053

Sequential associative memory with nonuniformity of the layer sizes.

PubMed

Teramae, Jun-Nosuke; Fukai, Tomoki

2007-01-01

Sequence retrieval has a fundamental importance in information processing by the brain, and has extensively been studied in neural network models. Most of the previous sequential associative memory embedded sequences of memory patterns have nearly equal sizes. It was recently shown that local cortical networks display many diverse yet repeatable precise temporal sequences of neuronal activities, termed "neuronal avalanches." Interestingly, these avalanches displayed size and lifetime distributions that obey power laws. Inspired by these experimental findings, here we consider an associative memory model of binary neurons that stores sequences of memory patterns with highly variable sizes. Our analysis includes the case where the statistics of these size variations obey the above-mentioned power laws. We study the retrieval dynamics of such memory systems by analytically deriving the equations that govern the time evolution of macroscopic order parameters. We calculate the critical sequence length beyond which the network cannot retrieve memory sequences correctly. As an application of the analysis, we show how the present variability in sequential memory patterns degrades the power-law lifetime distribution of retrieved neural activities.

A sequential multi-target Mps1 phosphorylation cascade promotes spindle checkpoint signaling.

PubMed

Ji, Zhejian; Gao, Haishan; Jia, Luying; Li, Bing; Yu, Hongtao

2017-01-10

The master spindle checkpoint kinase Mps1 senses kinetochore-microtubule attachment and promotes checkpoint signaling to ensure accurate chromosome segregation. The kinetochore scaffold Knl1, when phosphorylated by Mps1, recruits checkpoint complexes Bub1-Bub3 and BubR1-Bub3 to unattached kinetochores. Active checkpoint signaling ultimately enhances the assembly of the mitotic checkpoint complex (MCC) consisting of BubR1-Bub3, Mad2, and Cdc20, which inhibits the anaphase-promoting complex or cyclosome bound to Cdc20 (APC/C Cdc20 ) to delay anaphase onset. Using in vitro reconstitution, we show that Mps1 promotes APC/C inhibition by MCC components through phosphorylating Bub1 and Mad1. Phosphorylated Bub1 binds to Mad1-Mad2. Phosphorylated Mad1 directly interacts with Cdc20. Mutations of Mps1 phosphorylation sites in Bub1 or Mad1 abrogate the spindle checkpoint in human cells. Therefore, Mps1 promotes checkpoint activation through sequentially phosphorylating Knl1, Bub1, and Mad1. This sequential multi-target phosphorylation cascade makes the checkpoint highly responsive to Mps1 and to kinetochore-microtubule attachment.

Two New Real-Time PCR-based Surveillance Systems for “Candidatus Liberibacter” Species Detection

USDA-ARS?s Scientific Manuscript database

We developed two novel surveillance systems for “Candidatus Liberibacter” (CL) species detection and identification. The first system is called “single tube dual primer Taq-Man PCR” (STDP). The procedure involves two sequential rounds of PCR using the CL asiaticus species-specific outer and inner pr...

Special Education Administrators: Who and What Helps Buffer Job-Related Stress?

ERIC Educational Resources Information Center

Wheeler, Deborah S.; LaRocco, Diana J.

2009-01-01

The purpose of this study was to describe special education administrators' reports of the social supports (House, 1981) that ameliorate the stress inherent in their professional role. This study used a mixed methods design and was conducted in two sequential phases involving 153 special education administrators in a northeastern state. During…

Hierarchical Modeling of Sequential Behavioral Data: Examining Complex Association Patterns in Mediation Models

ERIC Educational Resources Information Center

Dagne, Getachew A.; Brown, C. Hendricks; Howe, George W.

2007-01-01

This article presents new methods for modeling the strength of association between multiple behaviors in a behavioral sequence, particularly those involving substantively important interaction patterns. Modeling and identifying such interaction patterns becomes more complex when behaviors are assigned to more than two categories, as is the case…

Report of Project on Development of a Curriculum Framework for Continuing Education in Nursing in Indiana.

ERIC Educational Resources Information Center

Schweer, Jean E., Ed.; Puetz, Belinda E., Ed.

A project involved development of a statewide generalized curriculum framework for continuing education in nursing by using an anticipatory approach to the selection of a coordinated, schematic arrangement of sequential course offerings by university-based centers for continuing education in nursing in Indiana. Following preliminary meetings of…

Sensor-Augmented Virtual Labs: Using Physical Interactions with Science Simulations to Promote Understanding of Gas Behavior

ERIC Educational Resources Information Center

Chao, Jie; Chiu, Jennifer L.; DeJaegher, Crystal J.; Pan, Edward A.

2016-01-01

Deep learning of science involves integration of existing knowledge and normative science concepts. Past research demonstrates that combining physical and virtual labs sequentially or side by side can take advantage of the unique affordances each provides for helping students learn science concepts. However, providing simultaneously connected…

The Relationship between Victimization at School and Achievement: The Cusp Catastrophe Model for Reading Performance

ERIC Educational Resources Information Center

Sideridis, Georgios D.; Antoniou, Faye; Stamovlasis, Dimitrios; Morgan, Paul L.

2013-01-01

We evaluated the relationship between victimization and academic achievement from a nonlinear perspective using a cusp catastrophe model. Participants were 62 students with identified learning disabilities (LD) using statewide criteria in Greece. Students participated in a 2-year cohort-sequential design. Reading assessments involved measures of…

School-Based Mutual Support Groups for Parents: An Intervention Guidebook.

ERIC Educational Resources Information Center

Simoni, Jane M.

This handbook focuses on steps and tasks related to establishing mutual support groups for parents in a school setting. A sequential approach is described that involves: working within the school to get started; recruiting members; training parents how to run their own meetings; and offering off-site consultation as requested. The first section…

A four-quadrant sequential streak technique to evaluate Campylobacter selective broths for suppressing background flora in broiler carcass rinses

USDA-ARS?s Scientific Manuscript database

The ecometric technique is a semi-quantitative scoring method used in the quality control of culture media in microbiology laboratories. This technique involves inoculation with defined populations of a specific culture onto solid media via a standardized chronological streaking technique, leading ...

Dynamic Processes at Semiconductor Interfaces: Atomic Intermixing, Diffusion Barriers, and Stability

DTIC Science & Technology

1991-08-15

that the movement of the Fermi level position at the Si surface and the variation of heterojunction band lineup correlated to the density of...that the topmost layer of As atoms was initially involved in a sequential two-step reaction to produce As l - and As 3+- like oxides. These reactions

Thinking in clinical nursing practice: a study of critical care nurses' thinking applying the think-aloud, protocol analysis method.

PubMed

Han, Kyung-Ja; Kim, Hesook Suzie; Kim, Mae-Ja; Hong, Kyung-Ja; Park, Sungae; Yun, Soon-Nyoung; Song, Misoon; Jung, Yoenyi; Kim, Haewon; Kim, Dong-Oak Debbie; Choi, Heejung; Kim, Kyungae

2007-06-01

The purpose of the paper is to discover the patterns and processes of decision-making in clinical nursing practice. A set of think-aloud data from five critical care nurses during 40 to 50 minutes of caregiving in intensive care units were obtained and analyzed by applying the procedures recommended by Ericsson and Simon for protocol analysis. Four thinking processes before acting were identified to constitute various sorts of thoughts in which the nurses were engaged during patient care: reviewing, validation, consideration, rationalization, and action. In addition, three patterns of sequential streaming of thinking (short, intermediate, long) were identified to reveal various ways the nurses dealt with clinical situations involving nursing tasks and responsibilities. This study specifies the initial categories of thoughts for each of the processes and various patterns with which these processes are sequentially combined, providing insights into the ways nurses think about problems and address their concerns. The findings suggest that the thinking in clinical practice involves more than focused decision-making and reasoning, and needs to be examined from a broader perspective.

Is Attention Shared Between the Ears?1

PubMed Central

Shiffrin, Richard M.; Pisoni, David B.; Castaneda-Mendez, Kicab

2012-01-01

This study tests the locus of attention during selective listening for speech-like stimuli. Can processing be differentially allocated to the two ears? Two conditions were used. The simultaneous condition involved one of four randomly chosen stop-consonants being presented to one of the ears chosen at random. The sequential condition involved two intervals; in the first S listened to the right ear; in the second S listened to the left ear. One of the four consonants was presented to an attended ear during one of these intervals. Experiment I used no distracting stimuli. Experiment II utilized a distracting consonant not confusable with any of the four target consonants. This distractor was always presented to any ear not containing a target. In both experiments, simultaneous and sequential performance were essentially identical, despite the need for attention sharing between the two ears during the simultaneous condition. We conclude that selective attention does not occur during perceptual processing of speech sounds presented to the two ears. We suggest that attentive effects arise in short-term memory following processing. PMID:23226838

Collagenous gastritis and collagenous colitis: a report with sequential histological and ultrastructural findings

PubMed Central

Pulimood, A; Ramakrishna, B; Mathan, M

1999-01-01

The case is reported of a young adult man with collagenous gastritis, an extremely rare disorder with only three case reports in the English literature, who subsequently presented with collagenous colitis. Sequential gastric biopsies showed a notable increase in thickness of the subepithelial collagen band. Ultrastructural study of gastric and rectal mucosa showed the characteristic subepithelial band composed of haphazardly arranged collagen fibres, prominent degranulating eosinophils, and activated pericryptal fibroblasts.


Keywords: collagenous gastritis; collagenous colitis; stomach; colon PMID:10323893

Sequencing and fan-out mechanism for causing a set of at least two sequential instructions to be performed in a dataflow processing computer

DOEpatents

Grafe, Victor G.; Hoch, James E.

1993-01-01

A sequencing and data fanout mechanism is provided for a dataflow processor is activated by an input token which causes a sequence of operations to occur by initiating a first instruction to act on data contained within the token and then executing a sequential thread of instructions identified by either a repeat count and an offset within the token, or by an offset within each preceding instruction.

Dopamine reward prediction-error signalling: a two-component response

PubMed Central

Schultz, Wolfram

2017-01-01

Environmental stimuli and objects, including rewards, are often processed sequentially in the brain. Recent work suggests that the phasic dopamine reward prediction-error response follows a similar sequential pattern. An initial brief, unselective and highly sensitive increase in activity unspecifically detects a wide range of environmental stimuli, then quickly evolves into the main response component, which reflects subjective reward value and utility. This temporal evolution allows the dopamine reward prediction-error signal to optimally combine speed and accuracy. PMID:26865020

Physical activity in England: who is meeting the recommended level of participation through sports and exercise?

PubMed

Anokye, Nana Kwame; Pokhrel, Subhash; Buxton, Martin; Fox-Rushby, Julia

2013-06-01

Little is known about the correlates of meeting recommended levels of participation in physical activity (PA) and how this understanding informs public health policies on behaviour change. To analyse who meets the recommended level of participation in PA in males and females separately by applying 'process' modelling frameworks (single vs. sequential 2-step process). Using the Health Survey for England 2006, (n = 14 142; ≥ 16 years), gender-specific regression models were estimated using bivariate probit with selectivity correction and single probit models. A 'sequential, 2-step process' modelled participation and meeting the recommended level separately, whereas the 'single process' considered both participation and level together. In females, meeting the recommended level was associated with degree holders [Marginal effect (ME) = 0.013] and age (ME = -0.001), whereas in males, age was a significant correlate (ME = -0.003 to -0.004). The order of importance of correlates was similar across genders, with ethnicity being the most important correlate in both males (ME = -0.060) and females (ME = -0.133). In females, the 'sequential, 2-step process' performed better (ρ = -0.364, P < 0.001) than that in males (ρ = 0.154). The degree to which people undertake the recommended level of PA through vigorous activity varies between males and females, and the process that best predicts such decisions, i.e. whether it is a sequential, 2-step process or a single-step choice, is also different for males and females. Understanding this should help to identify subgroups that are less likely to meet the recommended level of PA (and hence more likely to benefit from any PA promotion intervention).

Anti-tumor activity of high-dose EGFR tyrosine kinase inhibitor and sequential docetaxel in wild type EGFR non-small cell lung cancer cell nude mouse xenografts

PubMed Central

Tang, Ning; Zhang, Qianqian; Fang, Shu; Han, Xiao; Wang, Zhehai

2017-01-01

Treatment of non-small-cell lung cancer (NSCLC) with wild-type epidermal growth factor receptor (EGFR) is still a challenge. This study explored antitumor activity of high-dose icotinib (an EGFR tyrosine kinase inhibitor) plus sequential docetaxel against wild-type EGFR NSCLC cells-generated nude mouse xenografts. Nude mice were subcutaneously injected with wild-type EGFR NSCLC A549 cells and divided into different groups for 3-week treatment. Tumor xenograft volumes were monitored and recorded, and at the end of experiments, tumor xenografts were removed for Western blot and immunohistochemical analyses. Compared to control groups (negative control, regular-dose icotinib [IcoR], high-dose icotinib [IcoH], and docetaxel [DTX]) and regular icotinib dose (60 mg/kg) with docetaxel, treatment of mice with a high-dose (1200 mg/kg) of icotinib plus sequential docetaxel for 3 weeks (IcoH-DTX) had an additive effect on suppression of tumor xenograft size and volume (P < 0.05). Icotinib-containing treatments markedly reduced phosphorylation of EGFR, mitogen activated protein kinase (MAPK), and protein kinase B (Akt), but only the high-dose icotinib-containing treatments showed an additive effect on CD34 inhibition (P < 0.05), an indication of reduced microvessel density in tumor xenografts. Moreover, high-dose icotinib plus docetaxel had a similar effect on mouse weight loss (a common way to measure adverse reactions in mice), compared to the other treatment combinations. The study indicate that the high dose of icotinib plus sequential docetaxel (IcoH-DTX) have an additive effect on suppressing the growth of wild-type EGFR NSCLC cell nude mouse xenografts, possibly through microvessel density reduction. Future clinical trials are needed to confirm the findings of this study. PMID:27852073

A sequential analysis of classroom discourse in Italian primary schools: the many faces of the IRF pattern.

PubMed

Molinari, Luisa; Mameli, Consuelo; Gnisci, Augusto

2013-09-01

A sequential analysis of classroom discourse is needed to investigate the conditions under which the triadic initiation-response-feedback (IRF) pattern may host different teaching orientations. The purpose of the study is twofold: first, to describe the characteristics of classroom discourse and, second, to identify and explore the different interactive sequences that can be captured with a sequential statistical analysis. Twelve whole-class activities were video recorded in three Italian primary schools. We observed classroom interaction as it occurs naturally on an everyday basis. In total, we collected 587 min of video recordings. Subsequently, 828 triadic IRF patterns were extracted from this material and analysed with the programme Generalized Sequential Query (GSEQ). The results indicate that classroom discourse may unfold in different ways. In particular, we identified and described four types of sequences. Dialogic sequences were triggered by authentic questions, and continued through further relaunches. Monologic sequences were directed to fulfil the teachers' pre-determined didactic purposes. Co-constructive sequences fostered deduction, reasoning, and thinking. Scaffolding sequences helped and sustained children with difficulties. The application of sequential analyses allowed us to show that interactive sequences may account for a variety of meanings, thus making a significant contribution to the literature and research practice in classroom discourse. © 2012 The British Psychological Society.

Sequential intravenous injection of anionic polymer and cationic lipoplex of siRNA could effectively deliver siRNA to the liver.

PubMed

Hattori, Yoshiyuki; Arai, Shohei; Okamoto, Ryou; Hamada, Megumi; Kawano, Kumi; Yonemochi, Etsuo

2014-12-10

In this study, we developed novel siRNA transfer method to the liver by sequential intravenous injection of anionic polymer and cationic liposome/cholesterol-modified siRNA complex (cationic lipoplex). When cationic lipoplex was intravenously injected into mice, the accumulation of siRNA was mainly observed in the lungs. In contrast, when cationic lipoplex was intravenously injected at 1 min after intravenous injection of poly-L-glutamic acid (PGA) or chondroitin sulfate C (CS), siRNA was accumulated in the liver. In terms of suppression of gene expression in vivo, apolipoprotein B (ApoB) mRNA in the liver and low-density-lipoprotein (LDL) and very low-density-lipoprotein (VLDL) cholesterol level in serum were reduced at 48 h after single sequential injection of PGA or CS plus cationic lipoplex of cholesterol-modified ApoB siRNA. Furthermore, sequential injections of PGA plus cationic lipoplex of cholesterol-modified luciferase siRNA could reduce luciferase activity in tumor xenografts bearing liver metastasis of human breast tumor MCF-7-Luc. From these findings, sequential injection of anionic polymer and cationic lipoplex of siRNA might produce a systemic vector of siRNA to the liver. Copyright © 2014 Elsevier B.V. All rights reserved.

Sequential growth for lifetime extension in biomimetic polypyrrole actuator systems

NASA Astrophysics Data System (ADS)

Sarrazin, J. C.; Mascaro, Stephen A.

2015-04-01

Electroactive polymers (EAPs) present prospective use in actuation and manipulation devices due to their low electrical activation requirements, biocompatibility, and mechanical performance. One of the main drawbacks with EAP actuators is a decrease in performance over extended periods of operation caused by over-oxidation of the polymer and general polymer degradation. Synthesis of the EAP material, polypyrrole with an embedded metal helix allows for sequential growth of the polymer during operation. The helical metal electrode acts as a scaffolding to support the polymer, and direct the 3-dimensional change in volume of the polymer along the axis of the helix during oxidative and reductive cycling. The metal helix also provides a working metal electrode through the entire length of the polymer actuator to distribute charge for actuation, as well as for sequential growth steps during the lifetime of operation of the polymer. This work demonstrates the method of sequential growth can be utilized after extended periods of use to partially restore electrical and mechanical performance of polypyrrole actuators. Since the actuation must be temporarily stopped to allow for a sequential growth cycle to be performed and reverse some of the polymer degradation, these actuator systems more closely mimic natural muscle in their analogous maintenance and repair.

PHYSICAL EDUCATION FOR BOYS, GRADES 7-12.

ERIC Educational Resources Information Center

LEBOWITZ, GORDON; AND OTHERS

TEACHERS IN THE JUNIOR AND SENIOR HIGH SCHOOLS ARE PROVIDED WITH TEACHING OUTLINES, TEACHING DEVICES, AND OTHER MATERIALS TO DEVELOP PUPILS' SKILLS, APTITUDES, AND PROFICIENCY IN PHYSICAL ACTIVITIES AND SPORTS. A GRADED AND SEQUENTIAL DEVELOPMENT OF ACTIVITIES IN A UNIFIED PROGRAM, BASED UPON THE CONCEPT OF UNIT TEACHING IN SEASONAL ACTIVITIES, IS…

A high accuracy sequential solver for simulation and active control of a longitudinal combustion instability

NASA Technical Reports Server (NTRS)

Shyy, W.; Thakur, S.; Udaykumar, H. S.

1993-01-01

A high accuracy convection scheme using a sequential solution technique has been developed and applied to simulate the longitudinal combustion instability and its active control. The scheme has been devised in the spirit of the Total Variation Diminishing (TVD) concept with special source term treatment. Due to the substantial heat release effect, a clear delineation of the key elements employed by the scheme, i.e., the adjustable damping factor and the source term treatment has been made. By comparing with the first-order upwind scheme previously utilized, the present results exhibit less damping and are free from spurious oscillations, offering improved quantitative accuracy while confirming the spectral analysis reported earlier. A simple feedback type of active control has been found to be capable of enhancing or attenuating the magnitude of the combustion instability.

Characterization of the inhibitory effect of voriconazole on the fungicidal activity of amphotericin B against Candida albicans in an in vitro kinetic model.

PubMed

Lignell, Anders; Löwdin, Elisabeth; Cars, Otto; Sjölin, Jan

2008-07-01

The aim of the present investigation was to study and characterize the effect of voriconazole on the fungicidal activity of amphotericin B. Four strains of Candida albicans susceptible to voriconazole were exposed to voriconazole and amphotericin B, either alone, simultaneously or sequentially in an in vitro kinetic model. Bolus doses resulting in voriconazole and amphotericin B concentrations of 0.005-5 and 2.5 mg/L, respectively, were administered. Antifungal-containing RPMI 1640 was eliminated and replaced by a fresh medium using a peristaltic pump, with a flow rate adjusted to obtain the desired half-lives. With two drugs tested, a computer-controlled dosing pump compensated for differences in the elimination rates. Using static time-kill methodology, one C. albicans strain was exposed to 5 mg/L voriconazole for varying durations followed by 2.5 mg/L amphotericin B after three repeated washes of voriconazole. Voriconazole and amphotericin B treatment alone resulted in fungistatic and fungicidal activities, respectively. Simultaneous administration of voriconazole and amphotericin B resulted in fungicidal activity, whereas only fungistatic activity was observed when repeated doses of amphotericin B were administered sequentially after voriconazole at 24-96 h. The inhibition of the fungicidal activity of amphotericin B was voriconazole dose-dependent, but seemed to be recovered once the voriconazole concentration fell below the MIC. The fungicidal activity was quickly regained after the removal of voriconazole, irrespective of the duration of voriconazole pre-exposure. Voriconazole inhibited the fungicidal effect of sequentially administered amphotericin B in a concentration- and time-dependent manner; the clinical significance of this needs further investigation.

Monitoring Earth Surface Dynamics With Optical Imagery

NASA Astrophysics Data System (ADS)

Leprince, Sébastien; Berthier, Etienne; Ayoub, François; Delacourt, Christophe; Avouac, Jean-Philippe

2008-01-01

The increasing availability of high-quality optical satellite images should allow, in principle, continuous monitoring of Earth's surface changes due to geologic processes, climate change, or anthropic activity. For instance, sequential optical images have been used to measure displacements at Earth's surface due to coseismic ground deformation [e.g., Van Puymbroeck et al., 2000], ice flow [Scambos et al., 1992; Berthier et al., 2005], sand dune migration [Crippen, 1992], and landslides [Kääb, 2002; Delacourt et al., 2004]. Surface changes related to agriculture, deforestation, urbanization, and erosion-which do not involve ground displacement-might also be monitored, provided that the images can be registered with sufficient accuracy. Although the approach is simple in principle, its use is still limited, mainly because of geometric distortion of the images induced by the imaging system, biased correlation techniques, and implementation difficulties.

Perceived neighborhood walkability and physical exercise: An examination of casual communication in a social process.

PubMed

Yamamoto, Masahiro; Jo, Hyerim

2018-05-01

Despite the accumulated evidence for the environmental correlates of physical activity, social processes underlying this association are not entirely clear. This study positions communication characterized by weak ties as a social mechanism linking neighborhood walkability with physical exercise. Data from a survey of Chicago residents show that perceived neighborhood walkability is positively related to frequency of weak-tie communication. Frequency of weak-tie communication is related positively to perceived social cohesion and negatively to anonymity, both of which are significantly related to frequency of physical exercise in the neighborhood. Data also show a sequential indirect relationship involving perceived neighborhood walkability, weak-tie communication, anonymity, and physical exercise. Implications are discussed in terms of the role of communication in promoting locality-based physical exercise. Copyright © 2018 Elsevier Ltd. All rights reserved.

Molecular parameters of head and neck cancer metastasis

PubMed Central

Bhave, Sanjay L.; Teknos, Theodoros N.; Pan, Quintin; James, Arthur G.; Solove, Richard J.

2011-01-01

Metastasis remains a major cause of mortality in patients with head and neck squamous cell carcinoma (HNSCC). HNSCC patients with metastatic disease have extremely poor prognosis with survival rate of less than a year. Metastasis is an intricate sequential process which requires a discrete population of tumor cells to possess the capacity to intravasate from the primary tumor into systemic circulation, survive in circulation, extravasate at a distant site, and proliferate in a foreign hostile environment. Literature has accumulated to provide mechanistic insight into several signal transduction pathways, receptor tyrosine kinases (RTKs), signal transducer and activator of transcription 3 (Stat3), Rho GTPases, protein kinase Cε (PKCε), and nuclear factor-κB (NF-κB), that are involved in mediating a metastatic tumor cell phenotype in HNSCC. Here we highlight accrued information regarding the key molecular parameters of HNSCC metastasis. PMID:22077153

Design, Synthesis and Affinity Properties of Biologically Active Peptide and Protein Conjugates of Cotton Cellulose

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

Edwards, J. V.; Goheen, Steven C.

The formation of peptide and protein conjugates of cellulose on cotton fabrics provides promising leads for the development of wound healing, antibacterial, and decontaminating textiles. An approach to the design, synthesis, and analysis of bioconjugates containing cellulose peptide and protein conjugates includes: 1) computer graphic modeling for a rationally designed structure; 2) attachment of the peptide or protein to cotton cellulose through a linker amino acid, and 3) characterization of the resulting bioconjugate. Computer graphic simulation of protein and peptide cellulose conjugates gives a rationally designed biopolymer to target synthetic modifications to the cotton cellulose. Techniques for preparing these typesmore » of conjugates involve both sequential assembly of the peptide on the fabric and direct crosslinking of the peptide or protein as cellulose bound esters or carboxymethylcellulose amides.« less

A manual-based psychodynamic therapy for treatment-resistant borderline personality disorder.

PubMed

Gregory, Robert J; Remen, Anna L

2008-03-01

The authors introduce a manual-based treatment, labeled dynamic deconstructive psychotherapy, developed for those patients with borderline personality disorder who are most difficult to engage in therapy, such as those having co-occurring substance use disorders. This treatment model is based on the hypothesis that borderline pathology and related behaviors reflect impairment in specific neurocognitive functions, including association, attribution, and alterity that form the basis for a coherent and differentiated self. Dynamic deconstructive psychotherapy aims to activate and remediate neurocognitive self-capacities by facilitating elaboration of affect-laden interpersonal experiences and integration of attributions, as well as providing novel experiences in the patient-therapist relationship that promote self-other differentiation. Treatment involves weekly individual sessions for a predetermined period of time and follows sequential stages. (PsycINFO Database Record (c) 2010 APA, all rights reserved).

Axonal synapse sorting in medial entorhinal cortex

NASA Astrophysics Data System (ADS)

Schmidt, Helene; Gour, Anjali; Straehle, Jakob; Boergens, Kevin M.; Brecht, Michael; Helmstaedter, Moritz

2017-09-01

Research on neuronal connectivity in the cerebral cortex has focused on the existence and strength of synapses between neurons, and their location on the cell bodies and dendrites of postsynaptic neurons. The synaptic architecture of individual presynaptic axonal trees, however, remains largely unknown. Here we used dense reconstructions from three-dimensional electron microscopy in rats to study the synaptic organization of local presynaptic axons in layer 2 of the medial entorhinal cortex, the site of grid-like spatial representations. We observe path-length-dependent axonal synapse sorting, such that axons of excitatory neurons sequentially target inhibitory neurons followed by excitatory neurons. Connectivity analysis revealed a cellular feedforward inhibition circuit involving wide, myelinated inhibitory axons and dendritic synapse clustering. Simulations show that this high-precision circuit can control the propagation of synchronized activity in the medial entorhinal cortex, which is known for temporally precise discharges.

[Influence of "prehistory" of sequential movements of the right and the left hand on reproduction: coding of positions, movements and sequence structure].

PubMed

Bobrova, E V; Liakhovetskiĭ, V A; Borshchevskaia, E R

2011-01-01

The dependence of errors during reproduction of a sequence of hand movements without visual feedback on the previous right- and left-hand performance ("prehistory") and on positions in space of sequence elements (random or ordered by the explicit rule) was analyzed. It was shown that the preceding information about the ordered positions of the sequence elements was used during right-hand movements, whereas left-hand movements were performed with involvement of the information about the random sequence. The data testify to a central mechanism of the analysis of spatial structure of sequence elements. This mechanism activates movement coding specific for the left hemisphere (vector coding) in case of an ordered sequence structure and positional coding specific for the right hemisphere in case of a random sequence structure.

Amino acid selective unlabeling for sequence specific resonance assignments in proteins

PubMed Central

Krishnarjuna, B.; Jaipuria, Garima; Thakur, Anushikha

2010-01-01

Sequence specific resonance assignment constitutes an important step towards high-resolution structure determination of proteins by NMR and is aided by selective identification and assignment of amino acid types. The traditional approach to selective labeling yields only the chemical shifts of the particular amino acid being selected and does not help in establishing a link between adjacent residues along the polypeptide chain, which is important for sequential assignments. An alternative approach is the method of amino acid selective ‘unlabeling’ or reverse labeling, which involves selective unlabeling of specific amino acid types against a uniformly 13C/15N labeled background. Based on this method, we present a novel approach for sequential assignments in proteins. The method involves a new NMR experiment named, {12COi–15Ni+1}-filtered HSQC, which aids in linking the 1HN/15N resonances of the selectively unlabeled residue, i, and its C-terminal neighbor, i + 1, in HN-detected double and triple resonance spectra. This leads to the assignment of a tri-peptide segment from the knowledge of the amino acid types of residues: i − 1, i and i + 1, thereby speeding up the sequential assignment process. The method has the advantage of being relatively inexpensive, applicable to 2H labeled protein and can be coupled with cell-free synthesis and/or automated assignment approaches. A detailed survey involving unlabeling of different amino acid types individually or in pairs reveals that the proposed approach is also robust to misincorporation of 14N at undesired sites. Taken together, this study represents the first application of selective unlabeling for sequence specific resonance assignments and opens up new avenues to using this methodology in protein structural studies. Electronic supplementary material The online version of this article (doi:10.1007/s10858-010-9459-z) contains supplementary material, which is available to authorized users. PMID:21153044

A series of no isthmus (noi) alleles of the zebrafish pax2.1 gene reveals multiple signaling events in development of the midbrain-hindbrain boundary.

PubMed

Lun, K; Brand, M

1998-08-01

Generation of cell diversity in the vertebrate central nervous system starts during gastrulation stages in the ectodermal germ layer and involves specialized cell groups, such as the organizer located at the midbrain-hindbrain boundary (MHB). Mutations in the zebrafish no isthmus (noi) gene alter development of the MHB, and affect the pax2.1 gene (formerly pax(zf-b)). Analysis of the structure of pax2.1 reveals at least 12 normal splice variants. The noi alleles can be arranged, by molecular and phenotypic criteria, into a series of five alleles of differing strength, ranging from a null allele to weak alleles. In keeping with a role in development of the MHB organizer, gene expression is already affected in the MHB primordium of the gastrula neural ectoderm in noi mutants. eng3 activation is completely and eng2 activation is strongly dependent on noi function. In contrast, onset of wnt1, fgf8 and her5 expression occurs normally in the null mutants, but is eliminated later on. Our observations suggest that three signaling pathways, involving pax2.1, wnt1 and fgf8, are activated independently in early anterior-posterior patterning of this area. In addition, analysis of the allelic series unexpectedly suggests that noi activity is also required during dorsal-ventral patterning of the MHB in somitogenesis stages, and possibly in a later eng expression phase. We propose that noi/pax2.1 participates in sequential signaling processes as a key integrator of midbrain-hindbrain boundary development.

Changes in spinal reflex excitability associated with motor sequence learning.

PubMed

Lungu, Ovidiu; Frigon, Alain; Piché, Mathieu; Rainville, Pierre; Rossignol, Serge; Doyon, Julien

2010-05-01

There is ample evidence that motor sequence learning is mediated by changes in brain activity. Yet the question of whether this form of learning elicits changes detectable at the spinal cord level has not been addressed. To date, studies in humans have revealed that spinal reflex activity may be altered during the acquisition of various motor skills, but a link between motor sequence learning and changes in spinal excitability has not been demonstrated. To address this issue, we studied the modulation of H-reflex amplitude evoked in the flexor carpi radialis muscle of 14 healthy individuals between blocks of movements that involved the implicit acquisition of a sequence versus other movements that did not require learning. Each participant performed the task in three conditions: "sequence"-externally triggered, repeating and sequential movements, "random"-similar movements, but performed in an arbitrary order, and "simple"- involving alternating movements in a left-right or up-down direction only. When controlling for background muscular activity, H-reflex amplitude was significantly more reduced in the sequence (43.8 +/- 1.47%. mean +/- SE) compared with the random (38.2 +/- 1.60%) and simple (31.5 +/- 1.82%) conditions, while the M-response was not different across conditions. Furthermore, H-reflex changes were observed from the beginning of the learning process up to when subjects reached asymptotic performance on the motor task. Changes also persisted for >60 s after motor activity ceased. Such findings suggest that the excitability in some spinal reflex circuits is altered during the implicit learning process of a new motor sequence.

Dynamic Encoding of Speech Sequence Probability in Human Temporal Cortex

PubMed Central

Leonard, Matthew K.; Bouchard, Kristofer E.; Tang, Claire

2015-01-01

Sensory processing involves identification of stimulus features, but also integration with the surrounding sensory and cognitive context. Previous work in animals and humans has shown fine-scale sensitivity to context in the form of learned knowledge about the statistics of the sensory environment, including relative probabilities of discrete units in a stream of sequential auditory input. These statistics are a defining characteristic of one of the most important sequential signals humans encounter: speech. For speech, extensive exposure to a language tunes listeners to the statistics of sound sequences. To address how speech sequence statistics are neurally encoded, we used high-resolution direct cortical recordings from human lateral superior temporal cortex as subjects listened to words and nonwords with varying transition probabilities between sound segments. In addition to their sensitivity to acoustic features (including contextual features, such as coarticulation), we found that neural responses dynamically encoded the language-level probability of both preceding and upcoming speech sounds. Transition probability first negatively modulated neural responses, followed by positive modulation of neural responses, consistent with coordinated predictive and retrospective recognition processes, respectively. Furthermore, transition probability encoding was different for real English words compared with nonwords, providing evidence for online interactions with high-order linguistic knowledge. These results demonstrate that sensory processing of deeply learned stimuli involves integrating physical stimulus features with their contextual sequential structure. Despite not being consciously aware of phoneme sequence statistics, listeners use this information to process spoken input and to link low-level acoustic representations with linguistic information about word identity and meaning. PMID:25948269

Comparison of Coregistration Accuracy of Pelvic Structures Between Sequential and Simultaneous Imaging During Hybrid PET/MRI in Patients with Bladder Cancer.

PubMed

Rosenkrantz, Andrew B; Balar, Arjun V; Huang, William C; Jackson, Kimberly; Friedman, Kent P

2015-08-01

The aim of this study was to compare coregistration of the bladder wall, bladder masses, and pelvic lymph nodes between sequential and simultaneous PET and MRI acquisitions obtained during hybrid (18)F-FDG PET/MRI performed using a diuresis protocol in bladder cancer patients. Six bladder cancer patients underwent (18)F-FDG hybrid PET/MRI, including IV Lasix administration and oral hydration, before imaging to achieve bladder clearance. Axial T2-weighted imaging (T2WI) was obtained approximately 40 minutes before PET ("sequential") and concurrently with PET ("simultaneous"). Three-dimensional spatial coordinates of the bladder wall, bladder masses, and pelvic lymph nodes were recorded for PET and T2WI. Distances between these locations on PET and T2WI sequences were computed and used to compare in-plane (x-y plane) and through-plane (z-axis) misregistration relative to PET between T2WI acquisitions. The bladder increased in volume between T2WI acquisitions (sequential, 176 [139] mL; simultaneous, 255 [146] mL). Four patients exhibited a bladder mass, all with increased activity (SUV, 9.5-38.4). Seven pelvic lymph nodes in 4 patients showed increased activity (SUV, 2.2-9.9). The bladder wall exhibited substantially less misregistration relative to PET for simultaneous, compared with sequential, acquisitions in in-plane (2.8 [3.1] mm vs 7.4 [9.1] mm) and through-plane (1.7 [2.2] mm vs 5.7 [9.6] mm) dimensions. Bladder masses exhibited slightly decreased misregistration for simultaneous, compared with sequential, acquisitions in in-plane (2.2 [1.4] mm vs 2.6 [1.9] mm) and through-plane (0.0 [0.0] mm vs 0.3 [0.8] mm) dimensions. FDG-avid lymph nodes exhibited slightly decreased in-plane misregistration (1.1 [0.8] mm vs 2.5 [0.6] mm), although identical through-plane misregistration (4.0 [1.9] mm vs 4.0 [2.8] mm). Using hybrid PET/MRI, simultaneous imaging substantially improved bladder wall coregistration and slightly improved coregistration of bladder masses and pelvic lymph nodes.

Fractalkine and CX3CR1 Mediate a Novel Mechanism of Leukocyte Capture, Firm Adhesion, and Activation under Physiologic Flow

PubMed Central

Fong, Alan M.; Robinson, Lisa A.; Steeber, Douglas A.; Tedder, Thomas F.; Yoshie, Osamu; Imai, Toshio; Patel, Dhavalkumar D.

1998-01-01

Leukocyte migration into sites of inflammation involves multiple molecular interactions between leukocytes and vascular endothelial cells, mediating sequential leukocyte capture, rolling, and firm adhesion. In this study, we tested the role of molecular interactions between fractalkine (FKN), a transmembrane mucin-chemokine hybrid molecule expressed on activated endothelium, and its receptor (CX3CR1) in leukocyte capture, firm adhesion, and activation under physiologic flow conditions. Immobilized FKN fusion proteins captured resting peripheral blood mononuclear cells at physiologic wall shear stresses and induced firm adhesion of resting monocytes, resting and interleukin (IL)-2–activated CD8+ T lymphocytes and IL-2–activated NK cells. FKN also induced cell shape change in firmly adherent monocytes and IL-2–activated lymphocytes. CX3CR1-transfected K562 cells, but not control K562 cells, firmly adhered to FKN-expressing ECV-304 cells (ECV-FKN) and tumor necrosis factor α–activated human umbilical vein endothelial cells. This firm adhesion was not inhibited by pertussis toxin, EDTA/EGTA, or antiintegrin antibodies, indicating that the firm adhesion was integrin independent. In summary, FKN mediated the rapid capture, integrin-independent firm adhesion, and activation of circulating leukocytes under flow. Thus, FKN and CX3CR1 mediate a novel pathway for leukocyte trafficking. PMID:9782118

Plasmacytoid dendritic cells induce NK cell-dependent, tumor antigen-specific T cell cross-priming and tumor regression in mice.

PubMed

Liu, Chengwen; Lou, Yanyan; Lizée, Gregory; Qin, Hong; Liu, Shujuan; Rabinovich, Brian; Kim, Grace J; Wang, Yi-Hong; Ye, Yang; Sikora, Andrew G; Overwijk, Willem W; Liu, Yong-Jun; Wang, Gang; Hwu, Patrick

2008-03-01

A prerequisite for strong adaptive antiviral immunity is the robust initial activation of the innate immune system, which is frequently mediated by TLR-activated plasmacytoid DCs (pDCs). Natural antitumor immunity is often comparatively weak, potentially due to the lack of TLR-mediated activation signals within the tumor microenvironment. To assess whether pDCs are capable of directly facilitating effective antitumor immune responses, mice bearing established subcutaneous B16 melanoma tumors were administered TLR9-activated pDCs directly into the tumor. We found that TLR9-activated pDCs induced robust, spontaneous CTL cross-priming against multiple B16 tumor antigens, leading to the regression of both treated tumors and untreated tumors at distant contralateral sites. This T cell cross-priming was mediated by conventional DCs (cDCs) and was completely dependent upon the early recruitment and activation of NK cells at the tumor site. NK cell recruitment was mediated by CCR5 via chemokines secreted by pDCs, and optimal IFN-gamma production by NK cells was mediated by OX40L expressed by pDCs. Our data thus demonstrated that activated pDCs are capable of initiating effective and systemic antitumor immunity through the orchestration of an immune cascade involving the sequential activation of NK cells, cDCs, and CD8(+) T cells.

Sequential enzymatic epoxidation involved in polyether lasalocid biosynthesis.

PubMed

Minami, Atsushi; Shimaya, Mayu; Suzuki, Gaku; Migita, Akira; Shinde, Sandip S; Sato, Kyohei; Watanabe, Kenji; Tamura, Tomohiro; Oguri, Hiroki; Oikawa, Hideaki

2012-05-02

Enantioselective epoxidation followed by regioselective epoxide opening reaction are the key processes in construction of the polyether skeleton. Recent genetic analysis of ionophore polyether biosynthetic gene clusters suggested that flavin-containing monooxygenases (FMOs) could be involved in the oxidation steps. In vivo and in vitro analyses of Lsd18, an FMO involved in the biosynthesis of polyether lasalocid, using simple olefin or truncated diene of a putative substrate as substrate mimics demonstrated that enantioselective epoxidation affords natural type mono- or bis-epoxide in a stepwise manner. These findings allow us to figure out enzymatic polyether construction in lasalocid biosynthesis. © 2012 American Chemical Society

Brain mechanisms for perceptual and reward-related decision-making.

PubMed

Deco, Gustavo; Rolls, Edmund T; Albantakis, Larissa; Romo, Ranulfo

2013-04-01

Phenomenological models of decision-making, including the drift-diffusion and race models, are compared with mechanistic, biologically plausible models, such as integrate-and-fire attractor neuronal network models. The attractor network models show how decision confidence is an emergent property; and make testable predictions about the neural processes (including neuronal activity and fMRI signals) involved in decision-making which indicate that the medial prefrontal cortex is involved in reward value-based decision-making. Synaptic facilitation in these models can help to account for sequential vibrotactile decision-making, and for how postponed decision-related responses are made. The randomness in the neuronal spiking-related noise that makes the decision-making probabilistic is shown to be increased by the graded firing rate representations found in the brain, to be decreased by the diluted connectivity, and still to be significant in biologically large networks with thousands of synapses onto each neuron. The stability of these systems is shown to be influenced in different ways by glutamatergic and GABAergic efficacy, leading to a new field of dynamical neuropsychiatry with applications to understanding schizophrenia and obsessive-compulsive disorder. The noise in these systems is shown to be advantageous, and to apply to similar attractor networks involved in short-term memory, long-term memory, attention, and associative thought processes. Copyright © 2012 Elsevier Ltd. All rights reserved.

Accumulation of evidence during sequential decision making: the importance of top-down factors.

PubMed

de Lange, Floris P; Jensen, Ole; Dehaene, Stanislas

2010-01-13

In the last decade, great progress has been made in characterizing the accumulation of neural information during simple unitary perceptual decisions. However, much less is known about how sequentially presented evidence is integrated over time for successful decision making. The aim of this study was to study the mechanisms of sequential decision making in humans. In a magnetoencephalography (MEG) study, we presented healthy volunteers with sequences of centrally presented arrows. Sequence length varied between one and five arrows, and the accumulated directions of the arrows informed the subject about which hand to use for a button press at the end of the sequence (e.g., LRLRR should result in a right-hand press). Mathematical modeling suggested that nonlinear accumulation was the rational strategy for performing this task in the presence of no or little noise, whereas quasilinear accumulation was optimal in the presence of substantial noise. MEG recordings showed a correlate of evidence integration over parietal and central cortex that was inversely related to the amount of accumulated evidence (i.e., when more evidence was accumulated, neural activity for new stimuli was attenuated). This modulation of activity likely reflects a top-down influence on sensory processing, effectively constraining the influence of sensory information on the decision variable over time. The results indicate that, when making decisions on the basis of sequential information, the human nervous system integrates evidence in a nonlinear manner, using the amount of previously accumulated information to constrain the accumulation of additional evidence.

The effects of the sequential addition of synthesis parameters on the performance of alkali activated fly ash mortar

NASA Astrophysics Data System (ADS)

Dassekpo, Jean-Baptiste Mawulé; Zha, Xiaoxiong; Zhan, Jiapeng; Ning, Jiaqian

Geopolymer is an energy efficient and sustainable material that is currently used in construction industry as an alternative for Portland cement. As a new material, specific mix design method is essential and efforts have been made to develop a mix design procedure with the main focus on achieving better compressive strength and economy. In this paper, a sequential addition of synthesis parameters such as fly ash-sand, alkaline liquids, plasticizer and additional water at well-defined time intervals was investigated. A total of 4 mix procedures were used to study the compressive performance on fly ash-based geopolymer mortar and the results of each method were analyzed and discussed. Experimental results show that the sequential addition of sodium hydroxide (NaOH), sodium silicate (Na2SiO3), plasticizer (PL), followed by adding water (WA) increases considerably the compressive strengths of the geopolymer-based mortar. These results clearly demonstrate the high significant influence of sequential addition of synthesis parameters on geopolymer materials compressive properties, and also provide a new mixing method for the preparation of geopolymer paste, mortar and concrete.

Exploiting neurovascular coupling: a Bayesian sequential Monte Carlo approach applied to simulated EEG fNIRS data

NASA Astrophysics Data System (ADS)

Croce, Pierpaolo; Zappasodi, Filippo; Merla, Arcangelo; Chiarelli, Antonio Maria

2017-08-01

Objective. Electrical and hemodynamic brain activity are linked through the neurovascular coupling process and they can be simultaneously measured through integration of electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS). Thanks to the lack of electro-optical interference, the two procedures can be easily combined and, whereas EEG provides electrophysiological information, fNIRS can provide measurements of two hemodynamic variables, such as oxygenated and deoxygenated hemoglobin. A Bayesian sequential Monte Carlo approach (particle filter, PF) was applied to simulated recordings of electrical and neurovascular mediated hemodynamic activity, and the advantages of a unified framework were shown. Approach. Multiple neural activities and hemodynamic responses were simulated in the primary motor cortex of a subject brain. EEG and fNIRS recordings were obtained by means of forward models of volume conduction and light propagation through the head. A state space model of combined EEG and fNIRS data was built and its dynamic evolution was estimated through a Bayesian sequential Monte Carlo approach (PF). Main results. We showed the feasibility of the procedure and the improvements in both electrical and hemodynamic brain activity reconstruction when using the PF on combined EEG and fNIRS measurements. Significance. The investigated procedure allows one to combine the information provided by the two methodologies, and, by taking advantage of a physical model of the coupling between electrical and hemodynamic response, to obtain a better estimate of brain activity evolution. Despite the high computational demand, application of such an approach to in vivo recordings could fully exploit the advantages of this combined brain imaging technology.

What we know now: the Evanston Illinois field lineups.

PubMed

Steblay, Nancy K

2011-02-01

A Freedom of Information Act lawsuit secured 100 eyewitness identification reports from Evanston, Illinois, one of three cities of the Illinois Pilot Program. The files provide empirical evidence regarding three methodological aspects of the Program's comparison of non-blind simultaneous to double-blind sequential lineups. (1) A-priori differences existed between lineup conditions. For example, the simultaneous non-blind lineup condition was more likely to involve witnesses who had already identified the suspect in a previous lineup or who knew the offender (non-stranger identifications), and this condition also entailed shorter delays between event and lineup. (2) Verbatim eyewitness comments were recorded more often in double-blind sequential than in non-blind simultaneous lineup reports (83% vs. 39%). (3) Effective lineup structure was used equally in the two lineup conditions.

Multilevel Sequential Monte Carlo Samplers for Normalizing Constants

DOE PAGES

Moral, Pierre Del; Jasra, Ajay; Law, Kody J. H.; ...

2017-08-24

This article considers the sequential Monte Carlo (SMC) approximation of ratios of normalizing constants associated to posterior distributions which in principle rely on continuum models. Therefore, the Monte Carlo estimation error and the discrete approximation error must be balanced. A multilevel strategy is utilized to substantially reduce the cost to obtain a given error level in the approximation as compared to standard estimators. Two estimators are considered and relative variance bounds are given. The theoretical results are numerically illustrated for two Bayesian inverse problems arising from elliptic partial differential equations (PDEs). The examples involve the inversion of observations of themore » solution of (i) a 1-dimensional Poisson equation to infer the diffusion coefficient, and (ii) a 2-dimensional Poisson equation to infer the external forcing.« less

Particle connectedness and cluster formation in sequential depositions of particles: integral-equation theory.

PubMed

Danwanichakul, Panu; Glandt, Eduardo D

2004-11-15

We applied the integral-equation theory to the connectedness problem. The method originally applied to the study of continuum percolation in various equilibrium systems was modified for our sequential quenching model, a particular limit of an irreversible adsorption. The development of the theory based on the (quenched-annealed) binary-mixture approximation includes the Ornstein-Zernike equation, the Percus-Yevick closure, and an additional term involving the three-body connectedness function. This function is simplified by introducing a Kirkwood-like superposition approximation. We studied the three-dimensional (3D) system of randomly placed spheres and 2D systems of square-well particles, both with a narrow and with a wide well. The results from our integral-equation theory are in good accordance with simulation results within a certain range of densities.

Particle connectedness and cluster formation in sequential depositions of particles: Integral-equation theory

NASA Astrophysics Data System (ADS)

Danwanichakul, Panu; Glandt, Eduardo D.

2004-11-01

We applied the integral-equation theory to the connectedness problem. The method originally applied to the study of continuum percolation in various equilibrium systems was modified for our sequential quenching model, a particular limit of an irreversible adsorption. The development of the theory based on the (quenched-annealed) binary-mixture approximation includes the Ornstein-Zernike equation, the Percus-Yevick closure, and an additional term involving the three-body connectedness function. This function is simplified by introducing a Kirkwood-like superposition approximation. We studied the three-dimensional (3D) system of randomly placed spheres and 2D systems of square-well particles, both with a narrow and with a wide well. The results from our integral-equation theory are in good accordance with simulation results within a certain range of densities.

Concerted vs. Sequential. Two Activation Patterns of Vast Arrays of Intracellular Ca2+ Channels in Muscle

PubMed Central

Zhou, Jinsong; Brum, Gustavo; González, Adom; Launikonis, Bradley S.; Stern, Michael D.; Ríos, Eduardo

2005-01-01

To signal cell responses, Ca2+ is released from storage through intracellular Ca2+ channels. Unlike most plasmalemmal channels, these are clustered in quasi-crystalline arrays, which should endow them with unique properties. Two distinct patterns of local activation of Ca2+ release were revealed in images of Ca2+ sparks in permeabilized cells of amphibian muscle. In the presence of sulfate, an anion that enters the SR and precipitates Ca2+, sparks became wider than in the conventional, glutamate-based solution. Some of these were “protoplatykurtic” (had a flat top from early on), suggesting an extensive array of channels that activate simultaneously. Under these conditions the rate of production of signal mass was roughly constant during the rise time of the spark and could be as high as 5 μm3 ms−1, consistent with a release current >50 pA since the beginning of the event. This pattern, called “concerted activation,” was observed also in rat muscle fibers. When sulfate was combined with a reduced cytosolic [Ca2+] (50 nM) these sparks coexisted (and interfered) with a sequential progression of channel opening, probably mediated by Ca2+-induced Ca2+ release (CICR). Sequential propagation, observed only in frogs, may require parajunctional channels, of RyR isoform β, which are absent in the rat. Concerted opening instead appears to be a property of RyR α in the amphibian and the homologous isoform 1 in the mammal. PMID:16186560

Parents' School Satisfaction and Academic Socialization Predict Adolescents' Autonomous Motivation: A Mixed-Method Study of Low-Income Ethnic Minority Families

ERIC Educational Resources Information Center

Suizzo, Marie-Anne; Jackson, Karen Moran; Pahlke, Erin; McClain, Shannon; Marroquin, Yesenia; Blondeau, Lauren A.; Hong, KyongJoo

2016-01-01

In this mixed-methods study, we used an explanatory sequential design to investigate the processes through which parental involvement influences adolescents' achievement motivation. One hundred twenty low-income urban parents and their sixth-grade adolescents completed questionnaires, and a subsample of 11 mothers and 11 adolescents were…

Implementation of an Education Technology Policy in Namibia's High Schools: Through the Eyes of the Teacher

ERIC Educational Resources Information Center

Boer, Perien Joniell

2012-01-01

The purpose of this study was to explore how Namibian high school teachers experienced the ICT policy for education in their schools. This mixed methods sequential explanatory design consists of two distinct phases: quantitative followed by qualitative (Creswell & Plano Clark, 2011). Quantitative data collection involved the distribution and…

Training and Scoring Issues Involved in Large-Scale Writing Assessments.

ERIC Educational Resources Information Center

Moon, Tonya R.; Hughes, Kevin R.

2002-01-01

Examined a scoring anomaly that became apparent in a state-mandated writing assessment. Results for 3,660 essays by sixth graders show that using a spiral model for training raters and scoring papers results in higher mean ratings than does using a sequential model for training and scoring. Findings demonstrate the importance of making decisions…

Multipurpose Prepregging Machine

NASA Technical Reports Server (NTRS)

Johnston, N. J.; Wilkinson, Steven; Marchello, J. M.; Dixon, D.

1995-01-01

Machine designed and built for variety of uses involving coating or impregnating ("prepregging") fibers, tows, yarns, or webs or tapes made of such fibrous materials with thermoplastic or thermosetting resins. Prepreg materials produced used to make matrix/fiber composite materials. Comprises modules operated individually, sequentially, or simultaneously, depending on nature of specific prepreg material and prepregging technique used. Machine incorporates number of safety features.

Pyridine synthesis by reactions of allyl amines and alkynes proceeding through a Cu(OAc)2 oxidation and Rh(III)-catalyzed N-annulation sequence.

PubMed

Kim, Dong-Su; Park, Jung-Woo; Jun, Chul-Ho

2012-11-28

A new methodology has been developed for the synthesis of pyridines from allyl amines and alkynes, which involves sequential Cu(II)-promoted dehydrogenation of the allylamine and Rh(III)-catalyzed N-annulation of the resulting α,β-unsaturated imine and alkyne.

Motivating Factors for Teaching and Studying Music at Two-Year Colleges: A Survey of Faculty and Students

ERIC Educational Resources Information Center

Stewart, John R.; Williams, Yolanda Y.; Vu, Kinh T.; Collins, Tracey R.; Clementson, Casey J.; Berberick, David M.

2015-01-01

The purpose of this study was to explore what motivates faculty and student involvement in this educational environment and how student participation in music coursework contributes to current musical endeavors. The research team utilized a modified explanatory sequential mixed methods design to collect survey data and focus group data from…

Toward a Phonetic Representation of Signs, I: Sequentiality and Contrast

ERIC Educational Resources Information Center

Johnson, Robert E.; Liddell, Scott K.

2011-01-01

In this paper we examine the theory of the structure of signs that grew from Stokoe's (1965) proposals. We begin by examining argument for the structural simultaneity of signs by examining claims about how signs contrast and how cheremes function. Historically, such discussions have involved three claims: (1) that signs are composed of a single…

The Systemic Impacts of an Educational Project Conducted by One University in Partnership with Fifteen Organizations

ERIC Educational Resources Information Center

Arantes do Amaral, João Alberto; Frazão, Claudia Henriquez

2016-01-01

The systemic aspects of educational projects that involved universities, organizations and communities are issues that concern a number of researchers. In this paper, the authors present the processes and findings related to a one-year educational project. The educational project is accomplished through two sequential courses, which are taught by…

Educating Linguistically Diverse Students: A Mixed Methods Study of Elementary Teachers' Coursework, Attitudes, and Practice

ERIC Educational Resources Information Center

Greenfield, Renée A.

2016-01-01

This study followed a mixed-methods sequential explanatory design. Phase I involved the collection of quantitative data to examine inservice teachers' (N = 69) attitudes about language and linguistic diversity as well as their teacher education coursework. All participants were graduates from the same teacher education program. Phase II included…

ViSA: A Neurodynamic Model for Visuo-Spatial Working Memory, Attentional Blink, and Conscious Access

ERIC Educational Resources Information Center

Simione, Luca; Raffone, Antonino; Wolters, Gezinus; Salmas, Paola; Nakatani, Chie; Belardinelli, Marta Olivetti; van Leeuwen, Cees

2012-01-01

Two separate lines of study have clarified the role of selectivity in conscious access to visual information. Both involve presenting multiple targets and distracters: one "simultaneously" in a spatially distributed fashion, the other "sequentially" at a single location. To understand their findings in a unified framework, we propose a…

Getting a Jump on the Future: Everything You'll Ever Need to Know about Multimedia Authoring Tools.

ERIC Educational Resources Information Center

D'Ignazio, Fred

1992-01-01

Discusses issues involved with buying and using multimedia authoring programs. Six programs are compared: (1) MediaText, (2) HyperCard, (3) LinkWay Live!, (4) AmigaVision, (5) Director, and (6) Multimedia Desktop. Highlights include the use of multimedia in education, sequential versus hierarchical organization, price, system requirements, digital…

Maternal Mind-Mindedness and Children's School Readiness: A Longitudinal Study of Developmental Processes

ERIC Educational Resources Information Center

Bernier, Annie; McMahon, Catherine A.; Perrier, Rachel

2017-01-01

This study aimed to test a 5-wave sequential mediation model linking maternal mind-mindedness during infancy to children's school readiness in kindergarten through a serial mediation involving child language and effortful control in toddlerhood and the preschool years. Among a sample of 204 mother-child dyads, we assessed maternal mind-mindedness…

Benefits and Drawbacks of Using Multiple Instructors to Teach Single Courses

ERIC Educational Resources Information Center

Jones, Francis; Harris, Sara

2012-01-01

We set out to identify the benefits and drawbacks of using more than one instructor to teach single section science courses at a large research university. Nine courses were investigated involving widely differing subjects and levels. Teaching models included: sequential teaching with two to six instructors each covering only their own modules,…

PARENTS 2 study protocol: pilot of Parents' Active Role and ENgagement in the review of Their Stillbirth/perinatal death.

PubMed

Bakhbakhi, Danya; Siassakos, Dimitrios; Storey, Claire; Heazell, Alexander; Lynch, Mary; Timlin, Laura; Burden, Christy

2018-01-10

The perinatal mortality review meeting that takes place within the hospital following a stillbirth or neonatal death enables clinicians to learn vital lessons to improve care for women and their families for the future. Recent evidence suggests that parents are unaware that a formal review following the death of their baby takes place. Many would welcome the opportunity to feedback into the meeting itself. Parental involvement in the perinatal mortality review meeting has the potential to improve patient satisfaction, drive improvements in patient safety and promote an open culture within healthcare. Yet evidence on the feasibility of involving bereaved parents in the review process is lacking. This paper describes the protocol for the Parents' Active Role and Engangement iN the review of their Stillbirth/perinatal death study (PARENTS 2) , whereby healthcare professionals' and stakeholders' perceptions of parental involvement will be investigated, and parental involvement in the perinatal mortality review will be piloted and evaluated at two hospitals. We will investigate perceptions of parental involvement in the perinatal mortality review process by conducting four focus groups. A three-round modified Delphi technique will be employed to gain a consensus on principles of parental involvement in the perinatal mortality review process. We will use three sequential rounds, including a national consensus meeting workshop with experts in stillbirth, neonatal death and bereavement care, and a two-stage anonymous online questionnaire. We will pilot a new perinatal mortality review process with parental involvement over a 6-month study period. The impact of the new process will be evaluated by assessing parents' experiences of their care and parents' and staff perceptions of their involvement in the process by conducting further focus groups and using a Parent Generated Index questionnaire. This study has ethical approval from the UK Health Research Authority. We will disseminate the findings through national and international conferences and international peer-reviewed journals. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Right Brain Activities to Improve Analytical Thinking.

ERIC Educational Resources Information Center

Lynch, Marion E.

Schools tend to have a built-in bias toward left brain activities (tasks that are linear and sequential in nature), so the introduction of right brain activities (functions related to music, rhythm, images, color, imagination, daydreaming, dimensions) brings a balance into the classroom and helps those students who may be right brain oriented. To…

The Philosophical and Pedagogical Underpinnings of Active Learning in Engineering Education

ERIC Educational Resources Information Center

Christie, Michael; de Graaff, Erik

2017-01-01

In this paper the authors draw on three sequential keynote addresses that they gave at Active Learning in Engineering Education (ALE) workshops in Copenhagen (2012), Caxias do Sol (2014) and San Sebastian (2015). Active Learning in Engineering Education is an informal international network of engineering educators dedicated to improving…

A cascading activity-based probe sequentially targets E1–E2–E3 ubiquitin enzymes

PubMed Central

Mulder, Monique P.C.; Witting, Katharina; Berlin, Ilana; Pruneda, Jonathan N.; Wu, Kuen-Phon; Chang, Jer-Gung; Merkx, Remco; Bialas, Johanna; Groettrup, Marcus; Vertegaal, Alfred C.O.; Schulman, Brenda A.; Komander, David; Neefjes, Jacques; Oualid, Farid El; Ovaa, Huib

2016-01-01

Post-translational modifications of proteins with ubiquitin (Ub) and ubiquitin-like (Ubl) modifiers, orchestrated by a cascade of specialized E1, E2 and E3 enzymes, control a staggering breadth of cellular processes. To monitor catalysis along these complex reaction pathways, we developed a cascading activity-based probe, UbDha. Akin to the native Ub, upon ATP-dependent activation by the E1, UbDha can travel downstream to the E2 (and subsequently E3) enzymes through sequential trans-thioesterifications. Unlike the native Ub, at each step along the cascade UbDha has the option to react irreversibly with active site cysteine residues of target enzymes, thus enabling their detection. We show that our cascading probe ‘hops’ and ‘traps’ catalytically active ubiquitin-modifying enzymes (but not their substrates) by a mechanism diversifiable to Ubls. Our founder methodology, amenable to structural studies, proteome-wide profiling and monitoring of enzymatic activities in living cells, presents novel and versatile tools to interrogate the Ub/Ubl cascades. PMID:27182664

A collaborative sequential meta-analysis of individual patient data from randomized trials of endovascular therapy and tPA vs. tPA alone for acute ischemic stroke: ThRombEctomy And tPA (TREAT) analysis: statistical analysis plan for a sequential meta-analysis performed within the VISTA-Endovascular collaboration.

PubMed

MacIsaac, Rachael L; Khatri, Pooja; Bendszus, Martin; Bracard, Serge; Broderick, Joseph; Campbell, Bruce; Ciccone, Alfonso; Dávalos, Antoni; Davis, Stephen M; Demchuk, Andrew; Diener, Hans-Christoph; Dippel, Diederik; Donnan, Geoffrey A; Fiehler, Jens; Fiorella, David; Goyal, Mayank; Hacke, Werner; Hill, Michael D; Jahan, Reza; Jauch, Edward; Jovin, Tudor; Kidwell, Chelsea S; Liebeskind, David; Majoie, Charles B; Martins, Sheila Cristina Ouriques; Mitchell, Peter; Mocco, J; Muir, Keith W; Nogueira, Raul; Saver, Jeffrey L; Schonewille, Wouter J; Siddiqui, Adnan H; Thomalla, Götz; Tomsick, Thomas A; Turk, Aquilla S; White, Philip; Zaidat, Osama; Lees, Kennedy R

2015-10-01

Endovascular treatment has been shown to restore blood flow effectively. Second-generation medical devices such as stent retrievers are now showing overwhelming efficacy in clinical trials, particularly in conjunction with intravenous recombinant tissue plasminogen activator. This statistical analysis plan utilizing a novel, sequential approach describes a prospective, individual patient data analysis of endovascular therapy in conjunction with intravenous recombinant tissue plasminogen activator agreed upon by the Thrombectomy and Tissue Plasminogen Activator Collaborative Group. This protocol will specify the primary outcome for efficacy, as 'favorable' outcome defined by the ordinal distribution of the modified Rankin Scale measured at three-months poststroke, but with modified Rankin Scales 5 and 6 collapsed into a single category. The primary analysis will aim to answer the questions: 'what is the treatment effect of endovascular therapy with intravenous recombinant tissue plasminogen activator compared to intravenous tissue plasminogen activator alone on full scale modified Rankin Scale at 3 months?' and 'to what extent do key patient characteristics influence the treatment effect of endovascular therapy?'. Key secondary outcomes include effect of endovascular therapy on death within 90 days; analyses of modified Rankin Scale using dichotomized methods; and effects of endovascular therapy on symptomatic intracranial hemorrhage. Several secondary analyses will be considered as well as expanding patient cohorts to intravenous recombinant tissue plasminogen activator-ineligible patients, should data allow. This collaborative meta-analysis of individual participant data from randomized trials of endovascular therapy vs. control in conjunction with intravenous thrombolysis will demonstrate the efficacy and generalizability of endovascular therapy with intravenous thrombolysis as a concomitant medication. © 2015 World Stroke Organization.

A Sequential Approach in Treatment of Endo-Perio Lesion A Case Report

PubMed Central

Aspalli, Nagaveni; Munavalli, Anil; Ajgaonkar, Nishant; Babannavar, Roopa

2014-01-01

Endo-perio lesions primarily occur by way of the intimate anatomic and vascular connections between the pulp and the periodontium. Endodontic-periodontal combined lesion is a clinical dilemma because making a differential diagnosis and deciding a prognosis are difficult. An untreated primary endodontic lesion may become secondarily involved with periodontal breakdown, which clinically present unusual signs and symptoms. This may delay the diagnosis and hence the correct treatment. This case report describes diagnosis and treatment protocol for an endo-perio lesion of primary endodontic with secondary periodontal involvement. PMID:25302276

A sequential approach in treatment of endo-perio lesion a case report.

PubMed

Kambale, Sharanappa; Aspalli, Nagaveni; Munavalli, Anil; Ajgaonkar, Nishant; Babannavar, Roopa

2014-08-01

Endo-perio lesions primarily occur by way of the intimate anatomic and vascular connections between the pulp and the periodontium. Endodontic-periodontal combined lesion is a clinical dilemma because making a differential diagnosis and deciding a prognosis are difficult. An untreated primary endodontic lesion may become secondarily involved with periodontal breakdown, which clinically present unusual signs and symptoms. This may delay the diagnosis and hence the correct treatment. This case report describes diagnosis and treatment protocol for an endo-perio lesion of primary endodontic with secondary periodontal involvement.

Screening antimutagenic and antiproliferative properties of extracts isolated from Jackfruit pulp (Artocarpus heterophyllus Lam).

PubMed

Ruiz-Montañez, G; Burgos-Hernández, A; Calderón-Santoyo, M; López-Saiz, C M; Velázquez-Contreras, C A; Navarro-Ocaña, A; Ragazzo-Sánchez, J A

2015-05-15

The present focused on the study of the antimutagenic and antiproliferative potential of pulp Jackfruit (Artocarpus heterophyllus Lam) extract, using Salmonella typhimurium tester strains TA98 and TA100 with metabolic activation (S9) and a cancer cell line M12.C3.F6 (murine B-cell lymphoma), respectively. Jackfruit pulp extract was sequentially fractionated by chromatography (RP-HPLC) and each fraction was tested for antimutagenic and antiproliferative activities. The organic extracts obtained from Jackfruit pulp reduced the number of revertants caused by aflatoxin B1 (AFB1) and proliferation of cells M12.C3.F6; a dose-response relationship was showed. Sequential RP-HPLC fractionation of the active extracts produced both antimutagenic and/or antiproliferative fractions. These results suggested that the Jackfruit contained compounds with chemoprotective properties to reduce the mutagenicity of AFB1, also proliferation of a cancer cell line. Copyright © 2014 Elsevier Ltd. All rights reserved.

Quantitative evaluation of bone resorption activity of osteoclast-like cells by measuring calcium phosphate resorbing area using incubator-facilitated and video-enhanced microscopy.

PubMed

Morimoto, Yoshitaka; Hoshino, Hironobu; Sakurai, Takashi; Terakawa, Susumu; Nagano, Akira

2009-04-01

Quantitative evaluation of the ability of bone resorption activity in live osteoclast-like cells (OCLs) has not yet been reported on. In this study, we observed the sequential morphological change of OCLs and measured the resorbing calcium phosphate (CP) area made by OCLs alone and with the addition of elcatonin utilizing incubator facilitated video-enhanced microscopy. OCLs, which were obtained from a coculture of ddy-mouse osteoblastic cells and bone marrow cells, were cultured on CP-coated quartz cover slips. The CP-free area increased constantly in the OCLs alone, whereas it did not increase after the addition of elcatonin. This study showed that analysis of the resorbed areas under the OCL body using this method enables the sequential quantitative evaluation of the bone resorption activity and the effect of several therapeutic agents on bone resorption in vitro.

Putting the brakes on reproduction: Implications for conservation, global climate change and biomedicine.

PubMed

Wingfield, John C; Perfito, Nicole; Calisi, Rebecca; Bentley, George; Ubuka, T; Mukai, M; O'Brien, Sara; Tsutsui, K

2016-02-01

Seasonal breeding is widespread in vertebrates and involves sequential development of the gonads, onset of breeding activities (e.g. cycling in females) and then termination resulting in regression of the reproductive system. Whereas males generally show complete spermatogenesis prior to and after onset of breeding, females of many vertebrate species show only partial ovarian development and may delay onset of cycling (e.g. estrous), yolk deposition or germinal vesicle breakdown until conditions conducive for ovulation and onset of breeding are favorable. Regulation of this "brake" on the onset of breeding remains relatively unknown, but could have profound implications for conservation efforts and for "mismatches" of breeding in relation to global climate change. Using avian models it is proposed that a brain peptide, gonadotropin-inhibitory hormone (GnIH), may be the brake to prevent onset of breeding in females. Evidence to date suggests that although GnIH may be involved in the regulation of gonadal development and regression, it plays more regulatory roles in the process of final ovarian development leading to ovulation, transitions from sexual to parental behavior and suppression of reproductive function by environmental stress. Accumulating experimental evidence strongly suggests that GnIH inhibits actions of gonadotropin-releasing hormones on behavior (central effects), gonadotropin secretion (central and hypophysiotropic effects), and has direct actions in the gonad to inhibit steroidogenesis. Thus, actual onset of breeding activities leading to ovulation may involve environmental cues releasing an inhibition (brake) on the hypothalamo-pituitary-gonad axis. Copyright © 2015 Elsevier Inc. All rights reserved.

Outdoor Education Guide-Handbook, Waukesha Public Schools.

ERIC Educational Resources Information Center

Vitale, Joseph A.

Designed by the Waukesha Public Schools (Wisconsin) specifically for an elementary level three-day camping trip at Camp Phantom Lake, this outdoor education guide presents some activities which suggest adaptation. Activity directions, plans, worksheets, evaluation sheets, and illustrations are presented in sequential order for the following…

High-Efficiency Power Module

NASA Technical Reports Server (NTRS)

Simons, Rainee N (Inventor); Wintucky, Edwin G (Inventor)

2013-01-01

One or more embodiments of the present invention pertain to an all solid-state microwave power module. The module includes a plurality of solid-state amplifiers configured to amplify a signal using a low power stage, a medium power stage, and a high power stage. The module also includes a power conditioner configured to activate a voltage sequencer (e.g., bias controller) when power is received from a power source. The voltage sequencer is configured to sequentially apply voltage to a gate of each amplifier and sequentially apply voltage to a drain of each amplifier.

High-Efficiency Power Module

NASA Technical Reports Server (NTRS)

Simons, Rainee N. (Inventor); Wintucky, Edwin G. (Inventor)

2015-01-01

One or more embodiments of the present invention pertain to an all solid-state microwave power module. The module includes a plurality of solid-state amplifiers configured to amplify a signal using a low power stage, a medium power stage, and a high power stage. The module also includes a power conditioner configured to activate a voltage sequencer (e.g., bias controller) when power is received from a power source. The voltage sequencer is configured to sequentially apply voltage to a gate of each amplifier and sequentially apply voltage to a drain of each amplifier.

Impact of He and H relative depth distributions on the result of sequential He+ and H+ ion implantation and annealing in silicon

NASA Astrophysics Data System (ADS)

Cherkashin, N.; Daghbouj, N.; Seine, G.; Claverie, A.

2018-04-01

Sequential He++H+ ion implantation, being more effective than the sole implantation of H+ or He+, is used by many to transfer thin layers of silicon onto different substrates. However, due to the poor understanding of the basic mechanisms involved in such a process, the implantation parameters to be used for the efficient delamination of a superficial layer are still subject to debate. In this work, by using various experimental techniques, we have studied the influence of the He and H relative depth-distributions imposed by the ion energies onto the result of the sequential implantation and annealing of the same fluence of He and H ions. Analyzing the characteristics of the blister populations observed after annealing and deducing the composition of the gas they contain from FEM simulations, we show that the trapping efficiency of He atoms in platelets and blisters during annealing depends on the behavior of the vacancies generated by the two implants within the H-rich region before and after annealing. Maximum efficiency of the sequential ion implantation is obtained when the H-rich region is able to trap all implanted He ions, while the vacancies it generated are not available to favor the formation of V-rich complexes after implantation then He-filled nano-bubbles after annealing. A technological option is to implant He+ ions first at such an energy that the damage it generates is located on the deeper side of the H profile.

Differentiability of simulated MEG hippocampal, medial temporal and neocortical temporal epileptic spike activity.

PubMed

Stephen, Julia M; Ranken, Doug M; Aine, Cheryl J; Weisend, Michael P; Shih, Jerry J

2005-12-01

Previous studies have shown that magnetoencephalography (MEG) can measure hippocampal activity, despite the cylindrical shape and deep location in the brain. The current study extended this work by examining the ability to differentiate the hippocampal subfields, parahippocampal cortex, and neocortical temporal sources using simulated interictal epileptic activity. A model of the hippocampus was generated on the MRIs of five subjects. CA1, CA3, and dentate gyrus of the hippocampus were activated as well as entorhinal cortex, presubiculum, and neocortical temporal cortex. In addition, pairs of sources were activated sequentially to emulate various hypotheses of mesial temporal lobe seizure generation. The simulated MEG activity was added to real background brain activity from the five subjects and modeled using a multidipole spatiotemporal modeling technique. The waveforms and source locations/orientations for hippocampal and parahippocampal sources were differentiable from neocortical temporal sources. In addition, hippocampal and parahippocampal sources were differentiated to varying degrees depending on source. The sequential activation of hippocampal and parahippocampal sources was adequately modeled by a single source; however, these sources were not resolvable when they overlapped in time. These results suggest that MEG has the sensitivity to distinguish parahippocampal and hippocampal spike generators in mesial temporal lobe epilepsy.

Sequential delivery of TAT-HSP27 and VEGF using microsphere/hydrogel hybrid systems for therapeutic angiogenesis.

PubMed

Shin, Seung-Hwa; Lee, Jangwook; Lim, Kwang Suk; Rhim, Taiyoun; Lee, Sang Kyung; Kim, Yong-Hee; Lee, Kuen Yong

2013-02-28

Ischemic disease is associated with high mortality and morbidity rates, and therapeutic angiogenesis via systemic or local delivery of protein drugs is one potential approach to treat the disease. In this study, we hypothesized that combined delivery of TAT-HSP27 (HSP27 fused with transcriptional activator) and VEGF could enhance the therapeutic efficacy in an ischemic mouse model, and that sequential release could be critical in therapeutic angiogenesis. Alginate hydrogels containing TAT-HSP27 as an anti-apoptotic agent were prepared, and porous PLGA microspheres loaded with VEGF as an angiogenic agent were incorporated into the hydrogels to prepare microsphere/hydrogel hybrid delivery systems. Sequential in vitro release of TAT-HSP27 and VEGF was achieved by the hybrid systems. TAT-HSP27 was depleted from alginate gels in 7 days, while VEGF was continually released for 28 days. The release rate of VEGF was attenuated by varying the porous structures of PLGA microspheres. Sequential delivery of TAT-HSP27 and VEGF was critical to protect against muscle degeneration and fibrosis, as well as to promote new blood vessel formation in the ischemic site of a mouse model. This approach to controlling the sequential release behaviors of multiple drugs could be useful in the design of novel drug delivery systems for therapeutic angiogenesis. Copyright © 2012 Elsevier B.V. All rights reserved.

Let's 'play' with molecular pharmacology.

PubMed

Choudhury, Supriyo; Pradhan, Richeek; Sengupta, Gairik; Das, Manisha; Chatterjee, Manojit; Roy, Ranendra Kumar; Chatterjee, Suparna

2015-01-01

Understanding concepts of molecular mechanisms of drug action involves sequential visualization of physiological processes and drug effects, a task that can be difficult at an undergraduate level. Role-play is a teaching-learning methodology whereby active participation of students as well as clear visualization of the phenomenon is used to convey complex physiological concepts. However, its use in teaching drug action, a process that demands understanding of a second level of complexity over the physiological process, has not been investigated. We hypothesized that role-play can be an effective and well accepted method for teaching molecular pharmacology. In an observational study, students were guided to perform a role-play on a selected topic involving drug activity. Students' gain in knowledge was assessed comparing validated pre- and post-test questionnaires as well as class average normalized gain. The acceptance of role-play among undergraduate medical students was evaluated by Likert scale analysis and thematic analysis of their open-ended written responses. Significant improvement in knowledge (P < 0.001) was noted in the pre- to post-test knowledge scores, while a high gain in class average normalized score was evident. In Likert scale analysis, most students (93%) expressed that role-play was an acceptable way of teaching. In a thematic analysis, themes of both strengths and weaknesses of the session emerged. Role-play can be effectively utilized while teaching selected topics of molecular pharmacology in undergraduate medical curricula.

Binding intensity and metal partitioning in soils affected by mining and smelting activities in Minas Gerais, Brazil.

PubMed

Lopes, G; Costa, E T S; Penido, E S; Sparks, D L; Guilherme, L R G

2015-09-01

Mining and smelting activities are potential sources of heavy metal contamination, which pose a threat to human health and ecological systems. This study investigated single and sequential extractions of Zn, Pb, and Cd in Brazilian soils affected by mining and smelting activities. Soils from a Zn mining area (soils A, B, C, D, E, and the control soil) and a tailing from a smelting area were collected in Minas Gerais state, Brazil. The samples were subjected to single (using Mehlich I solution) and sequential extractions. The risk assessment code (RAC), the redistribution index (U ts ), and the reduced partition index (I R ) have been applied to the sequential extraction data. Zinc and Cd, in soil samples from the mining area, were found mainly associated with carbonate forms. This same pattern did not occur for Pb. Moreover, the Fe-Mn oxides and residual fractions had important contributions for Zn and Pb in those soils. For the tailing, more than 70 % of Zn and Cd were released in the exchangeable fraction, showing a much higher mobility and availability of these metals at this site, which was also supported by results of RAC and I R . These differences in terms of mobility might be due to different chemical forms of the metals in the two sites, which are attributable to natural occurrence as well as ore processing.

A sequential multi-target Mps1 phosphorylation cascade promotes spindle checkpoint signaling

PubMed Central

Ji, Zhejian; Gao, Haishan; Jia, Luying; Li, Bing; Yu, Hongtao

2017-01-01

The master spindle checkpoint kinase Mps1 senses kinetochore-microtubule attachment and promotes checkpoint signaling to ensure accurate chromosome segregation. The kinetochore scaffold Knl1, when phosphorylated by Mps1, recruits checkpoint complexes Bub1–Bub3 and BubR1–Bub3 to unattached kinetochores. Active checkpoint signaling ultimately enhances the assembly of the mitotic checkpoint complex (MCC) consisting of BubR1–Bub3, Mad2, and Cdc20, which inhibits the anaphase-promoting complex or cyclosome bound to Cdc20 (APC/CCdc20) to delay anaphase onset. Using in vitro reconstitution, we show that Mps1 promotes APC/C inhibition by MCC components through phosphorylating Bub1 and Mad1. Phosphorylated Bub1 binds to Mad1–Mad2. Phosphorylated Mad1 directly interacts with Cdc20. Mutations of Mps1 phosphorylation sites in Bub1 or Mad1 abrogate the spindle checkpoint in human cells. Therefore, Mps1 promotes checkpoint activation through sequentially phosphorylating Knl1, Bub1, and Mad1. This sequential multi-target phosphorylation cascade makes the checkpoint highly responsive to Mps1 and to kinetochore-microtubule attachment. DOI: http://dx.doi.org/10.7554/eLife.22513.001 PMID:28072388

Sequential parallel comparison design with binary and time-to-event outcomes.

PubMed

Silverman, Rachel Kloss; Ivanova, Anastasia; Fine, Jason

2018-04-30

Sequential parallel comparison design (SPCD) has been proposed to increase the likelihood of success of clinical trials especially trials with possibly high placebo effect. Sequential parallel comparison design is conducted with 2 stages. Participants are randomized between active therapy and placebo in stage 1. Then, stage 1 placebo nonresponders are rerandomized between active therapy and placebo. Data from the 2 stages are pooled to yield a single P value. We consider SPCD with binary and with time-to-event outcomes. For time-to-event outcomes, response is defined as a favorable event prior to the end of follow-up for a given stage of SPCD. We show that for these cases, the usual test statistics from stages 1 and 2 are asymptotically normal and uncorrelated under the null hypothesis, leading to a straightforward combined testing procedure. In addition, we show that the estimators of the treatment effects from the 2 stages are asymptotically normal and uncorrelated under the null and alternative hypothesis, yielding confidence interval procedures with correct coverage. Simulations and real data analysis demonstrate the utility of the binary and time-to-event SPCD. Copyright © 2018 John Wiley & Sons, Ltd.

Modulation of Re-initiation of Measles Virus Transcription at Intergenic Regions by PXD to NTAIL Binding Strength.

PubMed

Bloyet, Louis-Marie; Brunel, Joanna; Dosnon, Marion; Hamon, Véronique; Erales, Jenny; Gruet, Antoine; Lazert, Carine; Bignon, Christophe; Roche, Philippe; Longhi, Sonia; Gerlier, Denis

2016-12-01

Measles virus (MeV) and all Paramyxoviridae members rely on a complex polymerase machinery to ensure viral transcription and replication. Their polymerase associates the phosphoprotein (P) and the L protein that is endowed with all necessary enzymatic activities. To be processive, the polymerase uses as template a nucleocapsid made of genomic RNA entirely wrapped into a continuous oligomer of the nucleoprotein (N). The polymerase enters the nucleocapsid at the 3'end of the genome where are located the promoters for transcription and replication. Transcription of the six genes occurs sequentially. This implies ending and re-initiating mRNA synthesis at each intergenic region (IGR). We explored here to which extent the binding of the X domain of P (XD) to the C-terminal region of the N protein (NTAIL) is involved in maintaining the P/L complex anchored to the nucleocapsid template during the sequential transcription. Amino acid substitutions introduced in the XD-binding site on NTAIL resulted in a wide range of binding affinities as determined by combining protein complementation assays in E. coli and human cells and isothermal titration calorimetry. Molecular dynamics simulations revealed that XD binding to NTAIL involves a complex network of hydrogen bonds, the disruption of which by two individual amino acid substitutions markedly reduced the binding affinity. Using a newly designed, highly sensitive dual-luciferase reporter minigenome assay, the efficiency of re-initiation through the five measles virus IGRs was found to correlate with NTAIL/XD KD. Correlatively, P transcript accumulation rate and F/N transcript ratios from recombinant viruses expressing N variants were also found to correlate with the NTAIL to XD binding strength. Altogether, our data support a key role for XD binding to NTAIL in maintaining proper anchor of the P/L complex thereby ensuring transcription re-initiation at each intergenic region.

Modulation of Re-initiation of Measles Virus Transcription at Intergenic Regions by PXD to NTAIL Binding Strength

PubMed Central

Hamon, Véronique; Erales, Jenny; Bignon, Christophe; Roche, Philippe

2016-01-01

Measles virus (MeV) and all Paramyxoviridae members rely on a complex polymerase machinery to ensure viral transcription and replication. Their polymerase associates the phosphoprotein (P) and the L protein that is endowed with all necessary enzymatic activities. To be processive, the polymerase uses as template a nucleocapsid made of genomic RNA entirely wrapped into a continuous oligomer of the nucleoprotein (N). The polymerase enters the nucleocapsid at the 3’end of the genome where are located the promoters for transcription and replication. Transcription of the six genes occurs sequentially. This implies ending and re-initiating mRNA synthesis at each intergenic region (IGR). We explored here to which extent the binding of the X domain of P (XD) to the C-terminal region of the N protein (NTAIL) is involved in maintaining the P/L complex anchored to the nucleocapsid template during the sequential transcription. Amino acid substitutions introduced in the XD-binding site on NTAIL resulted in a wide range of binding affinities as determined by combining protein complementation assays in E. coli and human cells and isothermal titration calorimetry. Molecular dynamics simulations revealed that XD binding to NTAIL involves a complex network of hydrogen bonds, the disruption of which by two individual amino acid substitutions markedly reduced the binding affinity. Using a newly designed, highly sensitive dual-luciferase reporter minigenome assay, the efficiency of re-initiation through the five measles virus IGRs was found to correlate with NTAIL/XD KD. Correlatively, P transcript accumulation rate and F/N transcript ratios from recombinant viruses expressing N variants were also found to correlate with the NTAIL to XD binding strength. Altogether, our data support a key role for XD binding to NTAIL in maintaining proper anchor of the P/L complex thereby ensuring transcription re-initiation at each intergenic region. PMID:27936158

Electrospray ionization study of tricarbonyl fac-[Re(CO)3 (PO)(X)]-type complexes: influence of ancillary co-ligands in the release of carbon monoxide.

PubMed

Tisato, Francesco; Porchia, Marina; Shegani, Antoni; Maina, Theodosia; Papadopoulos, Minas S; Seraglia, Roberta; Traldi, Pietro

2018-05-08

fac-[Re(CO) 3 (PO)(X)]-type complexes (PO = chelated bidentate tertiary phosphine(1-), X = various neutral, mono-dentate ligands) represent a class of compounds that meets the synthetic criteria for the preparation of potential carbon monoxide (CO) release molecules (CORMs) for medicinal application. The aim of our investigation was to achieve qualitative information whether the nature of the ancillary X ligand might influence the release of CO. The release of CO has been investigated by means of product ion spectrometry of electrospray ionization-generated [M + H] + species, produced by multiple collisional experiments, using an ion trap mass spectrometer. Tandem mass spectrometry applied to the protonated species [Re(CO) 3 (PO)(X) + H] + of seven complexes (those including X = OH 2 (1), isonitrile (2, 3), imidazole (4), pyridine (5) and phosphine (6, 7) show initial loss of coordinated water (1) or pyridine (5), whereas the majority of investigated entries display initial, sequential release of CO groups. The energetics of CO release have been investigated by breakdown curves for selected collisionally-activated decomposition processes involving CO, and compared with those involving X groups. The nature of the co-ligand X drives the primary loss in the MS n processes of [Re(CO) 3 (PO)(X) + H] + compounds. When X = solvent, the energetics of these decompositions follow the trend H 2 O < MeOH < CO. In each case, loss of CO is a favored fragmentation route with associated energies following the trend: N-py ≤ P-phosphine < C-isonitrile. Overall, MS n pathways indicate that [Re(PO)] (Re with chelated PO phosphine) constitutes the residual moiety. This behavior indicates that the presence of a functionalized phosphine is essential for a sequential, controlled release of CO. This article is protected by copyright. All rights reserved.

The time course of auditory-visual processing of speech and body actions: evidence for the simultaneous activation of an extended neural network for semantic processing.

PubMed

Meyer, Georg F; Harrison, Neil R; Wuerger, Sophie M

2013-08-01

An extensive network of cortical areas is involved in multisensory object and action recognition. This network draws on inferior frontal, posterior temporal, and parietal areas; activity is modulated by familiarity and the semantic congruency of auditory and visual component signals even if semantic incongruences are created by combining visual and auditory signals representing very different signal categories, such as speech and whole body actions. Here we present results from a high-density ERP study designed to examine the time-course and source location of responses to semantically congruent and incongruent audiovisual speech and body actions to explore whether the network involved in action recognition consists of a hierarchy of sequentially activated processing modules or a network of simultaneously active processing sites. We report two main results:1) There are no significant early differences in the processing of congruent and incongruent audiovisual action sequences. The earliest difference between congruent and incongruent audiovisual stimuli occurs between 240 and 280 ms after stimulus onset in the left temporal region. Between 340 and 420 ms, semantic congruence modulates responses in central and right frontal areas. Late differences (after 460 ms) occur bilaterally in frontal areas.2) Source localisation (dipole modelling and LORETA) reveals that an extended network encompassing inferior frontal, temporal, parasaggital, and superior parietal sites are simultaneously active between 180 and 420 ms to process auditory–visual action sequences. Early activation (before 120 ms) can be explained by activity in mainly sensory cortices. . The simultaneous activation of an extended network between 180 and 420 ms is consistent with models that posit parallel processing of complex action sequences in frontal, temporal and parietal areas rather than models that postulate hierarchical processing in a sequence of brain regions. Copyright © 2013 Elsevier Ltd. All rights reserved.

Knowing what to respond in the future does not cancel the influence of past events.

PubMed

Tubau, Elisabet; López-Moliner, Joan

2009-05-29

Everyday tasks seldom involve isolate actions but sequences of them. We can see whether previous actions influence the current one by exploring the response time to controlled sequences of stimuli. Specifically, depending on the response-stimulus temporal interval (RSI), different mechanisms have been proposed to explain sequential effects in two-choice serial response tasks. Whereas an automatic facilitation mechanism is thought to produce a benefit for response repetitions at short RSIs, subjective expectancies are considered to replace the automatic facilitation at longer RSIs, producing a cost-benefit pattern: repetitions are faster after other repetitions but they are slower after alternations. However, there is not direct evidence showing the impact of subjective expectancies on sequential effects. By using a fixed sequence, the results of the reported experiment showed that the repetition effect was enhanced in participants who acquired complete knowledge of the order. Nevertheless, a similar cost-benefit pattern was observed in all participants and in all learning blocks. Therefore, results of the experiment suggest that sequential effects, including the cost-benefit pattern, are the consequence of automatic mechanisms which operate independently of (and simultaneously with) explicit knowledge of the sequence or other subjective expectancies.

Blunt pancreatic trauma: A persistent diagnostic conundrum?

PubMed Central

Kumar, Atin; Panda, Ananya; Gamanagatti, Shivanand

2016-01-01

Blunt pancreatic trauma is an uncommon injury but has high morbidity and mortality. In modern era of trauma care, pancreatic trauma remains a persistent challenge to radiologists and surgeons alike. Early detection of pancreatic trauma is essential to prevent subsequent complications. However early pancreatic injury is often subtle on computed tomography (CT) and can be missed unless specifically looked for. Signs of pancreatic injury on CT include laceration, transection, bulky pancreas, heterogeneous enhancement, peripancreatic fluid and signs of pancreatitis. Pan-creatic ductal injury is a vital decision-making parameter as ductal injury is an indication for laparotomy. While lacerations involving more than half of pancreatic parenchyma are suggestive of ductal injury on CT, ductal injuries can be directly assessed on magnetic resonance imaging (MRI) or encoscopic retrograde cholangio-pancreatography. Pancreatic trauma also shows temporal evolution with increase in extent of injury with time. Hence early CT scans may underestimate the extent of injures and sequential imaging with CT or MRI is important in pancreatic trauma. Sequential imaging is also needed for successful non-operative management of pancreatic injury. Accurate early detection on initial CT and adopting a multimodality and sequential imaging strategy can improve outcome in pancreatic trauma. PMID:26981225

The Doctrine of Original Antigenic Sin: Separating Good From Evil.

PubMed

Monto, Arnold S; Malosh, Ryan E; Petrie, Joshua G; Martin, Emily T

2017-06-15

The term "original antigenic sin" was coined approximately 60 years ago to describe the imprinting by the initial first influenza A virus infection on the antibody response to subsequent vaccination. These studies did not suggest a reduction in the response to current antigens but instead suggested anamnestic recall of antibody to earlier influenza virus strains. Then, approximately 40 years ago, it was observed that sequential influenza vaccination might lead to reduced vaccine effectiveness (VE). This conclusion was largely dismissed after an experimental study involving sequential administration of then-standard influenza vaccines. Recent observations have provided convincing evidence that reduced VE after sequential influenza vaccination is a real phenomenon. We propose that such reduction in VE be termed "negative antigenic interaction," given that there is no age cohort effect. In contrast, the potentially positive protective effect of early influenza virus infection later in life continues to be observed. It is essential that we understand better the immunologic factors underlying both original antigenic sin and negative antigenic interaction, to support development of improved influenza vaccines and vaccination strategies. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

Cascade catalysis in membranes with enzyme immobilization for multi-enzymatic conversion of CO2 to methanol.

PubMed

Luo, Jianquan; Meyer, Anne S; Mateiu, R V; Pinelo, Manuel

2015-05-25

Facile co-immobilization of enzymes is highly desirable for bioconversion methods involving multi-enzymatic cascade reactions. Here we show for the first time that three enzymes can be immobilized in flat-sheet polymeric membranes simultaneously or separately by simple pressure-driven filtration (i.e. by directing membrane fouling formation), without any addition of organic solvent. Such co-immobilization and sequential immobilization systems were examined for the production of methanol from CO2 with formate dehydrogenase (FDH), formaldehyde dehydrogenase (FaldDH) and alcohol dehydrogenase (ADH). Enzyme activity was fully retained by this non-covalent immobilization strategy. The two immobilization systems had similar catalytic efficiencies because the second reaction (formic acid→formaldehyde) catalyzed by FaldDH was found to be the cascade bottleneck (a threshold substrate concentration was required). Moreover, the trade-off between the mitigation of product inhibition and low substrate concentration for the adjacent enzymes probably made the co-immobilization meaningless. Thus, sequential immobilization could be used for multi-enzymatic cascade reactions, as it allowed the operational conditions for each single step to be optimized, not only during the enzyme immobilization but also during the reaction process, and the pressure-driven mass transfer (flow-through mode) could overcome the diffusion resistance between enzymes. This study not only offers a green and facile immobilization method for multi-enzymatic cascade systems, but also reveals the reaction bottleneck and provides possible solutions for the bioconversion of CO2 to methanol. Copyright © 2015 Elsevier B.V. All rights reserved.

A theory that may explain the Hayflick limit--a means to delete one copy of a repeating sequence during each cell cycle in certain human cells such as fibroblasts.

PubMed

Naveilhan, P; Baudet, C; Jabbour, W; Wion, D

1994-09-01

A model that may explain the limited division potential of certain cells such as human fibroblasts in culture is presented. The central postulate of this theory is that there exists, prior to certain key exons that code for materials needed for cell division, a unique sequence of specific repeating segments of DNA. One copy of such repeating segments is deleted during each cell cycle in cells that are not protected from such deletion through methylation of their cytosine residues. According to this theory, the means through which such repeated sequences are removed, one per cycle, is through the sequential action of enzymes that act much as bacterial restriction enzymes do--namely to produce scissions in both strands of DNA in areas that correspond to the DNA base sequence recognition specificities of such enzymes. After the first scission early in a replicative cycle, that enzyme becomes inhibited, but the cleavage of the first site exposes the closest site in the repetitive element to the action of a second restriction enzyme after which that enzyme also becomes inhibited. Then repair occurs, regenerating the original first site. Through this sequential activation and inhibition of two different restriction enzymes, only one copy of the repeating sequence is deleted during each cell cycle. In effect, the repeating sequence operates as a precise counter of the numbers of cell doubling that have occurred since the cells involved differentiated during development.

Multiple stage miniature stepping motor

DOEpatents

Niven, William A.; Shikany, S. David; Shira, Michael L.

1981-01-01

A stepping motor comprising a plurality of stages which may be selectively activated to effect stepping movement of the motor, and which are mounted along a common rotor shaft to achieve considerable reduction in motor size and minimum diameter, whereby sequential activation of the stages results in successive rotor steps with direction being determined by the particular activating sequence followed.

Associations between Children's Physical Activities, Sedentary Behaviours and Family Structure: A Sequential Mixed Methods Approach

ERIC Educational Resources Information Center

Quarmby, T.; Dagkas, S.; Bridge, M.

2011-01-01

This mixed method paper explored the effect of family structure on children's physical activities and sedentary pursuits. It furthers the limited understanding of how family structure impacts on children's time in, and reasons behind engaging in, certain physical activities. Children from three inner city comprehensive schools in the Midlands,…

Pi in the Sky: Hands-on Mathematical Activities for Teaching Astronomy.

ERIC Educational Resources Information Center

Pethoud, Robert

This book of activities was designed to provide students with the opportunity to create mental models of concepts in astronomy while using simple, homemade tools. In addition, these sequential, hands-on activities are to help students see how scientific knowledge is obtained. The introduction describes the rationale for the book and describes the…

Auto-Tandem Catalysis in Ionic Liquids: Synthesis of 2-Oxazolidinones by Palladium-Catalyzed Oxidative Carbonylation of Propargylic Amines in EmimEtSO₄.

PubMed

Mancuso, Raffaella; Maner, Asif; Ziccarelli, Ida; Pomelli, Christian; Chiappe, Cinzia; Della Ca', Nicola; Veltri, Lucia; Gabriele, Bartolo

2016-07-08

A convenient carbonylative approach to 2-oxazolidinone derivatives carried out using an ionic liquid (1-ethyl-3-methylimidazolium ethyl sulfate, EmimEtSO₄) as the solvent is presented. It is based on the sequential concatenation of two catalytic cycles, both catalyzed by the same metal species (auto-tandem catalysis): the first cycle corresponds to the oxidative monoaminocarbonylation of the triple bond of propargylic amines to give the corresponding 2-ynamide intermediates, while the second one involves the cyclocarbonylation of the latter to yield 2-(2-oxooxazolidin-5-ylidene)-acetamides. Reactions are carried out using a simple catalytic system consisting of PdI₂ in conjunction with an excess of KI, and the catalyst/solvent system could be recycled several times without appreciable loss of activity after extraction of the organic product with Et₂O.

Characterization of soluble glycoprotein D-mediated herpes simplex virus type 1 infection

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

Tsvitov, Marianna; Frampton, Arthur R.; Shah, Waris A.

2007-04-10

Herpes simplex virus type 1 (HSV-1) entry into permissive cells involves attachment to cell-surface glycosaminoglycans (GAGs) and fusion of the virus envelope with the cell membrane triggered by the binding of glycoprotein D (gD) to cognate receptors. In this study, we characterized the observation that soluble forms of the gD ectodomain (sgD) can mediate entry of gD-deficient HSV-1. We examined the efficiency and receptor specificity of this activity and used sequential incubation protocols to determine the order and stability of the initial interactions required for entry. Surprisingly, virus binding to GAGs did not increase the efficiency of sgD-mediated entry andmore » gD-deficient virus was capable of attaching to GAG-deficient cells in the absence of sgD. These observations suggested a novel binding interaction that may play a role in normal HSV infection.« less

Mesoporous gold sponges: electric charge-assisted seed mediated synthesis and application as surface-enhanced Raman scattering substrates

NASA Astrophysics Data System (ADS)

Yi, Zao; Luo, Jiangshan; Tan, Xiulan; Yi, Yong; Yao, Weitang; Kang, Xiaoli; Ye, Xin; Zhu, Wenkun; Duan, Tao; Yi, Yougen; Tang, Yongjian

2015-11-01

Mesoporous gold sponges were prepared using 4-dimethylaminopyridine (DMAP)-stabilized Au seeds. This is a general process, which involves a simple template-free method, room temperature reduction of HAuCl4·4H2O with hydroxylamine. The formation process of mesoporous gold sponges could be accounted for the electrostatic interaction (the small Au nanoparticles (~3 nm) and the positively charged DMAP-stabilized Au seeds) and Ostwald ripening process. The mesoporous gold sponges had appeared to undergo electrostatic adsorption initially, sequentially linear aggregation, welding and Ostwald ripening, then, they randomly cross link into self-supporting, three-dimensional networks with time. The mesoporous gold sponges exhibit higher surface area than the literature. In addition, application of the spongelike networks as an active material for surface-enhanced Raman scattering has been investigated by employing 4-aminothiophenol (4-ATP) molecules as a probe.

A symbolic/subsymbolic interface protocol for cognitive modeling

PubMed Central

Simen, Patrick; Polk, Thad

2009-01-01

Researchers studying complex cognition have grown increasingly interested in mapping symbolic cognitive architectures onto subsymbolic brain models. Such a mapping seems essential for understanding cognition under all but the most extreme viewpoints (namely, that cognition consists exclusively of digitally implemented rules; or instead, involves no rules whatsoever). Making this mapping reduces to specifying an interface between symbolic and subsymbolic descriptions of brain activity. To that end, we propose parameterization techniques for building cognitive models as programmable, structured, recurrent neural networks. Feedback strength in these models determines whether their components implement classically subsymbolic neural network functions (e.g., pattern recognition), or instead, logical rules and digital memory. These techniques support the implementation of limited production systems. Though inherently sequential and symbolic, these neural production systems can exploit principles of parallel, analog processing from decision-making models in psychology and neuroscience to explain the effects of brain damage on problem solving behavior. PMID:20711520

Mesoporous gold sponges: electric charge-assisted seed mediated synthesis and application as surface-enhanced Raman scattering substrates

PubMed Central

Yi, Zao; Luo, Jiangshan; Tan, Xiulan; Yi, Yong; Yao, Weitang; Kang, Xiaoli; Ye, Xin; Zhu, Wenkun; Duan, Tao; Yi, Yougen; Tang, Yongjian

2015-01-01

Mesoporous gold sponges were prepared using 4-dimethylaminopyridine (DMAP)-stabilized Au seeds. This is a general process, which involves a simple template-free method, room temperature reduction of HAuCl4·4H2O with hydroxylamine. The formation process of mesoporous gold sponges could be accounted for the electrostatic interaction (the small Au nanoparticles (~3 nm) and the positively charged DMAP-stabilized Au seeds) and Ostwald ripening process. The mesoporous gold sponges had appeared to undergo electrostatic adsorption initially, sequentially linear aggregation, welding and Ostwald ripening, then, they randomly cross link into self-supporting, three-dimensional networks with time. The mesoporous gold sponges exhibit higher surface area than the literature. In addition, application of the spongelike networks as an active material for surface-enhanced Raman scattering has been investigated by employing 4-aminothiophenol (4-ATP) molecules as a probe. PMID:26538365

Integration of Design, Thermal, Structural, and Optical Analysis, Including Thermal Animation

NASA Technical Reports Server (NTRS)

Amundsen, Ruth M.

1993-01-01

In many industries there has recently been a concerted movement toward 'quality management' and the issue of how to accomplish work more efficiently. Part of this effort is focused on concurrent engineering; the idea of integrating the design and analysis processes so that they are not separate, sequential processes (often involving design rework due to analytical findings) but instead form an integrated system with smooth transfers of information. Presented herein are several specific examples of concurrent engineering methods being carried out at Langley Research Center (LaRC): integration of thermal, structural and optical analyses to predict changes in optical performance based on thermal and structural effects; integration of the CAD design process with thermal and structural analyses; and integration of analysis and presentation by animating the thermal response of a system as an active color map -- a highly effective visual indication of heat flow.

Aurora kinase inhibitor AZD1152 has an additional effect of platinum on a sequential application at the human ovarian cancer cell line SKOV3.

PubMed

Ma, Yaxi; Weimer, Jörg; Fredrik, Regina; Adam-Klages, Sabine; Sebens, Susanne; Caliebe, Amke; Hilpert, Felix; Eckmann-Scholz, Christel; Arnold, Norbert; Schem, Christian

2013-07-01

The treatment of ovarian tumors is carried out with platinum medicine which can lead to incompatibilities or resistances. Thus, it is of great interest to check new medicine suitability for its application. AZD1152 is an Aurora kinase inhibitor predominantly works against Aurora kinase B involved in the chromosome segregation. Cells become polyploidy and reduce the proliferation by this impairment. To investigate whether AZD1152, may play a role in the treatment of ovarian carcinoma we serving it to the cisplatinum-resistant cell line SKOV3 alone and in combination with platinum. We look at the proliferation, the ploidy, the phases of cell cycle and the apoptosis activity of the cells. We could show that the combination of both medicines in the preclinical experiment produces a working advantage.

Dechlorination of 1,1,1-Trichloro-2,2-bis(p-chlorophenyl)ethane by Aerobacter aerogenes

USGS Publications Warehouse

Wedemeyer, Gary

1967-01-01

Whole cells or cell-free extracts of Aerobacter aerogenes catalyze the degradation of 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT) in vitro to at least seven metabolites: 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE); 1,1-dichloro-2,2-bis(p-chlorophenyl)ethane (DDD); 1-chloro-2,2-bis(p-chlorophenyl)ethylene (DDMU); 1-chloro-2,2-bis(p-chlorophenyl)ethane (DDMS); unsym-bis(p-chlorophenyl)ethylene (DDNU); 2,2-bis(p-chlorophenyl)acetate (DDA); and 4,4′-dichlorobenzophenone (DBP). The use of metabolic inhibitors together with pH and temperature studies indicated that discrete enzymes are involved. By use of the technique of sequential analysis, the metabolic pathway was shown to be: DDT → DDD →DDMU →DDMS → DDNU → DDA → DBP, or DDT → DDE. Dechlorination was marginally enhanced by light-activated flavin mononucleotide.

Fabrication of anticoagulation layer on titanium surface by sequential immobilization of poly (ethylene glycol) and albumin.

PubMed

Pan, Chang-Jiang; Hou, Yan-Hua; Zhang, Bin-Bin; Zhang, Lin-Cai

2014-01-01

This paper presents a simple method to sequentially immobilize poly (ethylene glycol) (PEG) and albumin on titanium surface to enhance the blood compatibility. Attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) analysis indicated that PEG and albumin were successfully immobilized on the titanium surface. Water contact angle results showed a better hydrophilic surface after the immobilization. The immobilized PEG or albumin can not only obviously prevent platelet adhesion and activation but also prolong activated partial thromboplastin time (APTT), leading to the improved anticoagulation. Moreover, immobilization of albumin on PEG-modified surface can further improve the anticoagulation. The approach in the present study provides an effective and efficient method to improve the anticoagulation of blood-contact biomedical devices such as coronary stents.

Competition between thyroid hormone receptor-associated protein (TRAP) 220 and transcriptional intermediary factor (TIF) 2 for binding to nuclear receptors. Implications for the recruitment of TRAP and p160 coactivator complexes.

PubMed

Treuter, E; Johansson, L; Thomsen, J S; Wärnmark, A; Leers, J; Pelto-Huikko, M; Sjöberg, M; Wright, A P; Spyrou, G; Gustafsson, J A

1999-03-05

Transcriptional activation by nuclear receptors (NRs) involves the concerted action of coactivators, chromatin components, and the basal transcription machinery. Crucial NR coactivators, which target primarily the conserved ligand-regulated activation (AF-2) domain, include p160 family members, such as TIF2, as well as p160-associated coactivators, such as CBP/p300. Because these coactivators possess intrinsic histone acetyltransferase activity, they are believed to function mainly by regulating chromatin-dependent transcriptional activation. Recent evidence suggests the existence of an additional NR coactivator complex, referred to as the thyroid hormone receptor-associated protein (TRAP) complex, which may function more directly as a bridging complex to the basal transcription machinery. TRAP220, the 220-kDa NR-binding subunit of the complex, has been identified in independent studies using both biochemical and genetic approaches. In light of the functional differences identified between p160 and TRAP coactivator complexes in NR activation, we have attempted to compare interaction and functional characteristics of TIF 2 and TRAP220. Our findings imply that competition between the NR-binding subunits of distinct coactivator complexes may act as a putative regulatory step in establishing either a sequential activation cascade or the formation of independent coactivator complexes.

Regioselective Cu(I)-catalyzed tandem A3-coupling/decarboxylative coupling to 3-amino-1,4-enynes.

PubMed

Feng, Huangdi; Ermolat'ev, Denis S; Song, Gonghua; Van der Eycken, Erik V

2012-04-06

An efficient and novel copper-mediated protocol for the synthesis of 3-amino-1,4-enynes from glyoxylic acid, an amine, and an alkyne was developed. This new reaction involving two sequential C-C bond formations is air and moisture tolerant and proceeds via a tandem A(3)-coupling and a selective decarboxylative coupling.

Exploring the Learner's Knowledge Construction and Cognitive Patterns of Different Asynchronous Platforms: Comparison of an Online Discussion Forum and Facebook

ERIC Educational Resources Information Center

Hou, Huei-Tse; Wang, Shu-Ming; Lin, Peng-Chun; Chang, Kuo-En

2015-01-01

The primary purpose of this study is to explore the knowledge construction behaviour and cognitive patterns involved in students' online discussion using online forum and Facebook (FB). This study employed quantitative content analysis and lag sequential analysis to examine the content and behavioural patterns of 50 students from a private…

Pulse-echo probe of rock permeability near oil wells

NASA Technical Reports Server (NTRS)

Narasimhan, K. Y.; Parthasarathy, S. P.

1978-01-01

Processing method involves sequential insonifications of borehole wall at number of different frequencies. Return signals are normalized in amplitude, and root-mean-square (rms) value of each signal is determined. Values can be processed to yield information on size and number density of microfractures at various depths in rock matrix by using averaging methods developed for pulse-echo technique.

The Effects of Multiple Exemplar Training on a Working Memory Task Involving Sequential Responding in Children with Autism

ERIC Educational Resources Information Center

Baltruschat, Lisa; Hasselhorn, Marcus; Tarbox, Jonathan; Dixon, Dennis R.; Najdowski, Adel; Mullins, Ryan David; Gould, Evelyn

2012-01-01

This study is part of a programmatic line of research into the use of basic positive reinforcement procedures for improving working memory in children with autism spectrum disorders. The authors evaluated the effects of multiple exemplar training, utilizing positive reinforcement, on performance of a "digit span backwards" task--a test of working…

Music: Grades Five through Eight. Black Swamp Arts Scene Course of Study: Talented and Gifted.

ERIC Educational Resources Information Center

Defiance County Office of Education, OH.

This course of study was developed for intermediate and junior high students in the Defiance (Ohio) public schools who are talented and gifted in music, providing for an indepth and sequential development of the skills and concepts involved. The program's philosophy stresses that, while the products of the arts are important, a need exists to…

Is a Basketball Free-Throw Sequence Nonrandom? A Group Exercise for Undergraduate Statistics Students

ERIC Educational Resources Information Center

Adolph, Stephen C.

2007-01-01

I describe a group exercise that I give to my undergraduate biostatistics class. The exercise involves analyzing a series of 200 consecutive basketball free-throw attempts to determine whether there is any evidence for sequential dependence in the probability of making a free-throw. The students are given the exercise before they have learned the…

Student Teachers' Team Teaching: How Do Learners in the Classroom Experience Team-Taught Lessons by Student Teachers?

ERIC Educational Resources Information Center

Baeten, Marlies; Simons, Mathea

2016-01-01

This study focuses on student teachers' team teaching. Two team teaching models (sequential and parallel teaching) were applied by 14 student teachers in a quasi-experimental design. When implementing new teaching models, it is important to take into account the perspectives of all actors involved. Although learners are key actors in the teaching…

Flynn effects on sub-factors of episodic and semantic memory: parallel gains over time and the same set of determining factors.

PubMed

Rönnlund, Michael; Nilsson, Lars-Göran

2009-09-01

The study examined the extent to which time-related gains in cognitive performance, so-called Flynn effects, generalize across sub-factors of episodic memory (recall and recognition) and semantic memory (knowledge and fluency). We conducted time-sequential analyses of data drawn from the Betula prospective cohort study, involving four age-matched samples (35-80 years; N=2996) tested on the same battery of memory tasks on either of four occasions (1989, 1995, 1999, and 2004). The results demonstrate substantial time-related improvements on recall and recognition as well as on fluency and knowledge, with a trend of larger gains on semantic as compared with episodic memory [Rönnlund, M., & Nilsson, L. -G. (2008). The magnitude, generality, and determinants of Flynn effects on forms of declarative memory: Time-sequential analyses of data from a Swedish cohort study. Intelligence], but highly similar gains across the sub-factors. Finally, the association with markers of environmental change was similar, with evidence that historical increases in quantity of schooling was a main driving force behind the gains, both on the episodic and semantic sub-factors. The results obtained are discussed in terms of brain regions involved.

Studying the Effect of Deposition Conditions on the Performance and Reliability of MEMS Gas Sensors

PubMed Central

Sadek, Khaled; Moussa, Walied

2007-01-01

In this paper, the reliability of a micro-electro-mechanical system (MEMS)-based gas sensor has been investigated using Three Dimensional (3D) coupled multiphysics Finite Element (FE) analysis. The coupled field analysis involved a two-way sequential electrothermal fields coupling and a one-way sequential thermal-structural fields coupling. An automated substructuring code was developed to reduce the computational cost involved in simulating this complicated coupled multiphysics FE analysis by up to 76 percent. The substructured multiphysics model was then used to conduct a parametric study of the MEMS-based gas sensor performance in response to the variations expected in the thermal and mechanical characteristics of thin films layers composing the sensing MEMS device generated at various stages of the microfabrication process. Whenever possible, the appropriate deposition variables were correlated in the current work to the design parameters, with good accuracy, for optimum operation conditions of the gas sensor. This is used to establish a set of design rules, using linear and nonlinear empirical relations, which can be utilized in real-time at the design and development decision-making stages of similar gas sensors to enable the microfabrication of these sensors with reliable operation.

The enigma of nonarteritic anterior ischemic optic neuropathy: an update for the comprehensive ophthalmologist.

PubMed

Gaier, Eric D; Torun, Nurhan

2016-11-01

Nonarteritic anterior ischemic optic neuropathy (NAION) is the most common cause of acute optic nerve injury, and frequently presents to comprehensive ophthalmologists. We review the typical and atypical clinical features and current literature on various treatment modalities for NAION. The epidemiology and clinical presentation of this disease can be variable, making a definitive diagnosis difficult in many cases. In addition, the differential diagnoses for this disorder, although comprising much less prevalent entities, are quite broad and can have substantial systemic implications if these alternatives go unrecognized. NAION has many systemic associations and comorbidities that deserve inquiry when the diagnosis is made. There are currently no widely accepted, evidence-based treatments for NAION. All recommendations made to patients to reduce their risk of sequential eye involvement, including avoidance of potential nocturnal hypotension, erectile dysfunction medication, and treatment of obstructive sleep apnea, have theoretical bases. NAION is a common cause of acute vision loss in adult and older patients, and thus, comprehensive ophthalmologists need to be able to diagnose and appropriately manage this disorder. We anticipate fruitful results from current and future trials aimed at neuroprotection in the affected eye and prevention of sequential eye involvement.

Characteristics of vertigo and the affected vestibular nerve systems in idiopathic bilateral vestibulopathy.

PubMed

Fujimoto, Chisato; Kinoshita, Makoto; Kamogashira, Teru; Egami, Naoya; Sugasawa, Keiko; Yamasoba, Tatsuya; Iwasaki, Shinichi

2016-01-01

Vertigo attacks in IBV patients involving both the superior and inferior vestibular nerve systems were significantly more severe than vertigo attacks in patients with selective involvement of the inferior vestibular nerve system alone. To investigate the relationship between the frequency and duration of vertigo and the affected vestibular nerve system in idiopathic bilateral vestibulopathy (IBV). This study categorized 44 IBV patients into the following three sub-groups according to the affected vestibular nerve system: superior, inferior, and mixed type. These patients were also categorized into the following three sub-groups according to their clinical time course: progressive type showing no episodes of vertigo, sequential type showing recurrent vertigo attacks and single-attack type showing a single episode of vertigo. Ten, 11 and 23 patients were classified as the superior, the inferior, and the mixed type, respectively. Seventeen, 23, and four patients were classified as the progressive, the sequential, and the single-attack type, respectively. For the patients having one or more vertigo attacks, the duration of the vertigo attack was longer than 24 h in 69% of the mixed type, and the duration of vertigo in the mixed type was significantly longer than that in the inferior type (p < 0.05).

Energy-Water Nexus: Balancing the Tradeoffs between Two-Level Decision Makers

DOE PAGES

Zhang, Xiaodong; Vesselinov, Velimir Valentinov

2016-09-03

Energy-water nexus has substantially increased importance in the recent years. Synergistic approaches based on systems-analysis and mathematical models are critical for helping decision makers better understand the interrelationships and tradeoffs between energy and water. In energywater nexus management, various decision makers with different goals and preferences, which are often conflicting, are involved. These decision makers may have different controlling power over the management objectives and the decisions. They make decisions sequentially from the upper level to the lower level, challenging decision making in energy-water nexus. In order to address such planning issues, a bi-level decision model is developed, which improvesmore » upon the existing studies by integration of bi-level programming into energy-water nexus management. The developed model represents a methodological contribution to the challenge of sequential decisionmaking in energy-water nexus through provision of an integrated modeling framework/tool. An interactive fuzzy optimization methodology is introduced to seek a satisfactory solution to meet the overall satisfaction of the two-level decision makers. The tradeoffs between the two-level decision makers in energy-water nexus management are effectively addressed and quantified. Application of the proposed model to a synthetic example problem has demonstrated its applicability in practical energy-water nexus management. Optimal solutions for electricity generation, fuel supply, water supply including groundwater, surface water and recycled water, capacity expansion of the power plants, and GHG emission control are generated. In conclusion, these analyses are capable of helping decision makers or stakeholders adjust their tolerances to make informed decisions to achieve the overall satisfaction of energy-water nexus management where bi-level sequential decision making process is involved.« less

Energy-Water Nexus: Balancing the Tradeoffs between Two-Level Decision Makers

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

Zhang, Xiaodong; Vesselinov, Velimir Valentinov

Energy-water nexus has substantially increased importance in the recent years. Synergistic approaches based on systems-analysis and mathematical models are critical for helping decision makers better understand the interrelationships and tradeoffs between energy and water. In energywater nexus management, various decision makers with different goals and preferences, which are often conflicting, are involved. These decision makers may have different controlling power over the management objectives and the decisions. They make decisions sequentially from the upper level to the lower level, challenging decision making in energy-water nexus. In order to address such planning issues, a bi-level decision model is developed, which improvesmore » upon the existing studies by integration of bi-level programming into energy-water nexus management. The developed model represents a methodological contribution to the challenge of sequential decisionmaking in energy-water nexus through provision of an integrated modeling framework/tool. An interactive fuzzy optimization methodology is introduced to seek a satisfactory solution to meet the overall satisfaction of the two-level decision makers. The tradeoffs between the two-level decision makers in energy-water nexus management are effectively addressed and quantified. Application of the proposed model to a synthetic example problem has demonstrated its applicability in practical energy-water nexus management. Optimal solutions for electricity generation, fuel supply, water supply including groundwater, surface water and recycled water, capacity expansion of the power plants, and GHG emission control are generated. In conclusion, these analyses are capable of helping decision makers or stakeholders adjust their tolerances to make informed decisions to achieve the overall satisfaction of energy-water nexus management where bi-level sequential decision making process is involved.« less

Using Priced Options to Solve the Exposure Problem in Sequential Auctions

NASA Astrophysics Data System (ADS)

Mous, Lonneke; Robu, Valentin; La Poutré, Han

This paper studies the benefits of using priced options for solving the exposure problem that bidders with valuation synergies face when participating in multiple, sequential auctions. We consider a model in which complementary-valued items are auctioned sequentially by different sellers, who have the choice of either selling their good directly or through a priced option, after fixing its exercise price. We analyze this model from a decision-theoretic perspective and we show, for a setting where the competition is formed by local bidders, that using options can increase the expected profit for both buyers and sellers. Furthermore, we derive the equations that provide minimum and maximum bounds between which a synergy buyer's bids should fall in order for both sides to have an incentive to use the options mechanism. Next, we perform an experimental analysis of a market in which multiple synergy bidders are active simultaneously.

Optimization of enzyme-assisted improvement of polyphenols and free radical scavenging activity in red rice bran: A statistical and neural network-based approach.

PubMed

Prabhu, Ashish A; Jayadeep, A

2017-04-21

The current study is focused on optimizing the parameters involved in enzymatic processing of red rice bran for maximizing total polyphenol (TP) and free radical scavenging activity (FRSA). The sequential optimization strategies using central composite design (CCD) and artificial neural network (ANN) modeling linked with genetic algorithm (GA) was performed to study the effect of incubation time (60-90 min), xylanase concentration (5-10 mg/g), cellulase concentration (5-10 mg/g) on the response, i.e., total polyphenol and FRSA. The result showed that incubation time has a negative effect on the response, while the square effect of xylanase and cellulase showed positive effect on the response. A maximum TP of 2,761 mg ferulic acid Eq/100 g bran and FRSA of 778.4 mg Catechin Eq/100 g bran was achieved with incubation time (min) = 60.491; xylanase (mg/g) = 5.4633; cellulase (mg/g) = 11.5825. Furthermore, ANN-GA-based optimization showed better predicting capabilities as compared to CCD.

Effects of practice on variability in an isochronous serial interval production task: asymptotical levels of tapping variability after training are similar to those of musicians.

PubMed

Madison, Guy; Karampela, Olympia; Ullén, Fredrik; Holm, Linus

2013-05-01

Timing permeates everyday activities such as walking, dancing and music, yet the effect of short-term practice in this ubiquitous activity is largely unknown. In two training experiments involving sessions spread across several days, we examined short-term practice effects on timing variability in a sequential interval production task. In Experiment 1, we varied the mode of response (e.g., drumstick and finger tapping) and the level of sensory feedback. In Experiment 2 we varied the interval in 18 levels ranging from 500 ms to 1624 ms. Both experiments showed a substantial decrease in variability within the first hour of practice, but little thereafter. This effect was similar across mode of response, amount of feedback, and interval duration, and was manifested as a reduction in both local variability (between neighboring intervals) and drift (fluctuation across multiple intervals). The results suggest mainly effects on motor implementation rather than on cognitive timing processes, and have methodological implications for timing studies that have not controlled for practice. Copyright © 2013 Elsevier B.V. All rights reserved.

Giant Virus Megavirus chilensis Encodes the Biosynthetic Pathway for Uncommon Acetamido Sugars*

PubMed Central

Piacente, Francesco; De Castro, Cristina; Jeudy, Sandra; Molinaro, Antonio; Salis, Annalisa; Damonte, Gianluca; Bernardi, Cinzia; Abergel, Chantal; Tonetti, Michela G.

2014-01-01

Giant viruses mimicking microbes, by the sizes of their particles and the heavily glycosylated fibrils surrounding their capsids, infect Acanthamoeba sp., which are ubiquitous unicellular eukaryotes. The glycans on fibrils are produced by virally encoded enzymes, organized in gene clusters. Like Mimivirus, Megavirus glycans are mainly composed of virally synthesized N-acetylglucosamine (GlcNAc). They also contain N-acetylrhamnosamine (RhaNAc), a rare sugar; the enzymes involved in its synthesis are encoded by a gene cluster specific to Megavirus close relatives. We combined activity assays on two enzymes of the pathway with mass spectrometry and NMR studies to characterize their specificities. Mg534 is a 4,6-dehydratase 5-epimerase; its three-dimensional structure suggests that it belongs to a third subfamily of inverting dehydratases. Mg535, next in the pathway, is a bifunctional 3-epimerase 4-reductase. The sequential activity of the two enzymes leads to the formation of UDP-l-RhaNAc. This study is another example of giant viruses performing their glycan synthesis using enzymes different from their cellular counterparts, raising again the question of the origin of these pathways. PMID:25035429

Functional identification of MdSIZ1 as a SUMO E3 ligase in apple.

PubMed

Zhang, Rui-Fen; Guo, Ying; Li, Yuan-Yuan; Zhou, Li-Jie; Hao, Yu-Jin; You, Chun-Xiang

2016-07-01

SUMOylation, the conjugation of target proteins with SUMO (small ubiquitin-related modifier), is a type of post-translational modification in eukaryotes and involves the sequential action of activation (E1), conjugation (E2) and ligation (E3) enzymes. In Arabidopsis, the AtSIZ1 protein is a SUMO E3 ligase that promotes the conjugation of SUMO proteins to target substrates. Here, we isolated and identified a SUMO E3 ligase, MdSIZ1, in apple, which was similar to AtSIZ1. SUMOylation analysis showed that MdSIZ1 had SUMO E3 ligase activity in vitro and in vivo. SUMO conjugation was increased by high temperatures, low temperatures, and abscisic acid (ABA). The ectopic expression of MdSIZ1 in Arabidopsis siz1-2 mutant plants partially complemented the morphological mutant phenotype and enhanced the levels of SUMO conjugation. Taken together, these results suggest that MdSIZ1-mediated SUMO conjugation of target proteins is an important process that regulates the adaptation of apple plants to various environmental stresses. Copyright © 2016 Elsevier GmbH. All rights reserved.

Neural correlates of trust.

PubMed

Krueger, Frank; McCabe, Kevin; Moll, Jorge; Kriegeskorte, Nikolaus; Zahn, Roland; Strenziok, Maren; Heinecke, Armin; Grafman, Jordan

2007-12-11

Trust is a critical social process that helps us to cooperate with others and is present to some degree in all human interaction. However, the underlying brain mechanisms of conditional and unconditional trust in social reciprocal exchange are still obscure. Here, we used hyperfunctional magnetic resonance imaging, in which two strangers interacted online with one another in a sequential reciprocal trust game while their brains were simultaneously scanned. By designing a nonanonymous, alternating multiround game, trust became bidirectional, and we were able to quantify partnership building and maintenance. Using within- and between-brain analyses, an examination of functional brain activity supports the hypothesis that the preferential activation of different neuronal systems implements these two trust strategies. We show that the paracingulate cortex is critically involved in building a trust relationship by inferring another person's intentions to predict subsequent behavior. This more recently evolved brain region can be differently engaged to interact with more primitive neural systems in maintaining conditional and unconditional trust in a partnership. Conditional trust selectively activated the ventral tegmental area, a region linked to the evaluation of expected and realized reward, whereas unconditional trust selectively activated the septal area, a region linked to social attachment behavior. The interplay of these neural systems supports reciprocal exchange that operates beyond the immediate spheres of kinship, one of the distinguishing features of the human species.

Neural correlates of trust

PubMed Central

Krueger, Frank; McCabe, Kevin; Moll, Jorge; Kriegeskorte, Nikolaus; Zahn, Roland; Strenziok, Maren; Heinecke, Armin; Grafman, Jordan

2007-01-01

Trust is a critical social process that helps us to cooperate with others and is present to some degree in all human interaction. However, the underlying brain mechanisms of conditional and unconditional trust in social reciprocal exchange are still obscure. Here, we used hyperfunctional magnetic resonance imaging, in which two strangers interacted online with one another in a sequential reciprocal trust game while their brains were simultaneously scanned. By designing a nonanonymous, alternating multiround game, trust became bidirectional, and we were able to quantify partnership building and maintenance. Using within- and between-brain analyses, an examination of functional brain activity supports the hypothesis that the preferential activation of different neuronal systems implements these two trust strategies. We show that the paracingulate cortex is critically involved in building a trust relationship by inferring another person's intentions to predict subsequent behavior. This more recently evolved brain region can be differently engaged to interact with more primitive neural systems in maintaining conditional and unconditional trust in a partnership. Conditional trust selectively activated the ventral tegmental area, a region linked to the evaluation of expected and realized reward, whereas unconditional trust selectively activated the septal area, a region linked to social attachment behavior. The interplay of these neural systems supports reciprocal exchange that operates beyond the immediate spheres of kinship, one of the distinguishing features of the human species. PMID:18056800

Post-conventional moral reasoning is associated with increased ventral striatal activity at rest and during task.

PubMed

Fang, Zhuo; Jung, Wi Hoon; Korczykowski, Marc; Luo, Lijuan; Prehn, Kristin; Xu, Sihua; Detre, John A; Kable, Joseph W; Robertson, Diana C; Rao, Hengyi

2017-08-02

People vary considerably in moral reasoning. According to Kohlberg's theory, individuals who reach the highest level of post-conventional moral reasoning judge moral issues based on deeper principles and shared ideals rather than self-interest or adherence to laws and rules. Recent research has suggested the involvement of the brain's frontostriatal reward system in moral judgments and prosocial behaviors. However, it remains unknown whether moral reasoning level is associated with differences in reward system function. Here, we combined arterial spin labeling perfusion and blood oxygen level-dependent functional magnetic resonance imaging and measured frontostriatal reward system activity both at rest and during a sequential risky decision making task in a sample of 64 participants at different levels of moral reasoning. Compared to individuals at the pre-conventional and conventional level of moral reasoning, post-conventional individuals showed increased resting cerebral blood flow in the ventral striatum and ventromedial prefrontal cortex. Cerebral blood flow in these brain regions correlated with the degree of post-conventional thinking across groups. Post-conventional individuals also showed greater task-induced activation in the ventral striatum during risky decision making. These findings suggest that high-level post-conventional moral reasoning is associated with increased activity in the brain's frontostriatal system, regardless of task-dependent or task-independent states.

Neuronal Activation After Prolonged Immobilization: Do the Same or Different Neurons Respond to a Novel Stressor?

PubMed

Marín-Blasco, Ignacio; Muñoz-Abellán, Cristina; Andero, Raül; Nadal, Roser; Armario, Antonio

2018-04-01

Despite extensive research on the impact of emotional stressors on brain function using immediate-early genes (e.g., c-fos), there are still important questions that remain unanswered such as the reason for the progressive decline of c-fos expression in response to prolonged stress and the neuronal populations activated by different stressors. This study tackles these 2 questions by evaluating c-fos expression in response to 2 different emotional stressors applied sequentially, and performing a fluorescent double labeling of c-Fos protein and c-fos mRNA on stress-related brain areas. Results were complemented with the assessment of the hypothalamic-pituitary-adrenal axis activation. We showed that the progressive decline of c-fos expression could be related to 2 differing mechanisms involving either transcriptional repression or changes in stimulatory inputs. Moreover, the neuronal populations that respond to the different stressors appear to be predominantly separated in high-level processing areas (e.g., medial prefrontal cortex). However, in low-hierarchy areas (e.g., paraventricular nucleus of the hypothalamus) neuronal populations appear to respond unspecifically. The data suggest that the distinct physiological and behavioral consequences of emotional stressors, and their implication in the development of psychopathologies, are likely to be closely associated with neuronal populations specifically activated by each stressor.

Sequential inhibitory control processes assessed through simultaneous EEG-fMRI.

PubMed

Baumeister, Sarah; Hohmann, Sarah; Wolf, Isabella; Plichta, Michael M; Rechtsteiner, Stefanie; Zangl, Maria; Ruf, Matthias; Holz, Nathalie; Boecker, Regina; Meyer-Lindenberg, Andreas; Holtmann, Martin; Laucht, Manfred; Banaschewski, Tobias; Brandeis, Daniel

2014-07-01

Inhibitory response control has been extensively investigated in both electrophysiological (ERP) and hemodynamic (fMRI) studies. However, very few multimodal results address the coupling of these inhibition markers. In fMRI, response inhibition has been most consistently linked to activation of the anterior insula and inferior frontal cortex (IFC), often also the anterior cingulate cortex (ACC). ERP work has established increased N2 and P3 amplitudes during NoGo compared to Go conditions in most studies. Previous simultaneous EEG-fMRI imaging reported association of the N2/P3 complex with activation of areas like the anterior midcingulate cortex (aMCC) and anterior insula. In this study we investigated inhibitory control in 23 healthy young adults (mean age=24.7, n=17 for EEG during fMRI) using a combined Flanker/NoGo task during simultaneous EEG and fMRI recording. Separate fMRI and ERP analysis yielded higher activation in the anterior insula, IFG and ACC as well as increased N2 and P3 amplitudes during NoGo trials in accordance with the literature. Combined analysis modelling sequential N2 and P3 effects through joint parametric modulation revealed correlation of higher N2 amplitude with deactivation in parts of the default mode network (DMN) and the cingulate motor area (CMA) as well as correlation of higher central P3 amplitude with activation of the left anterior insula, IFG and posterior cingulate. The EEG-fMRI results resolve the localizations of these sequential activations. They suggest a general role for allocation of attentional resources and motor inhibition for N2 and link memory recollection and internal reflection to P3 amplitude, in addition to previously described response inhibition as reflected by the anterior insula. Copyright © 2014 Elsevier Inc. All rights reserved.

A GPU-Based Implementation of the Firefly Algorithm for Variable Selection in Multivariate Calibration Problems

PubMed Central

de Paula, Lauro C. M.; Soares, Anderson S.; de Lima, Telma W.; Delbem, Alexandre C. B.; Coelho, Clarimar J.; Filho, Arlindo R. G.

2014-01-01

Several variable selection algorithms in multivariate calibration can be accelerated using Graphics Processing Units (GPU). Among these algorithms, the Firefly Algorithm (FA) is a recent proposed metaheuristic that may be used for variable selection. This paper presents a GPU-based FA (FA-MLR) with multiobjective formulation for variable selection in multivariate calibration problems and compares it with some traditional sequential algorithms in the literature. The advantage of the proposed implementation is demonstrated in an example involving a relatively large number of variables. The results showed that the FA-MLR, in comparison with the traditional algorithms is a more suitable choice and a relevant contribution for the variable selection problem. Additionally, the results also demonstrated that the FA-MLR performed in a GPU can be five times faster than its sequential implementation. PMID:25493625

A GPU-Based Implementation of the Firefly Algorithm for Variable Selection in Multivariate Calibration Problems.

PubMed

de Paula, Lauro C M; Soares, Anderson S; de Lima, Telma W; Delbem, Alexandre C B; Coelho, Clarimar J; Filho, Arlindo R G

2014-01-01

Several variable selection algorithms in multivariate calibration can be accelerated using Graphics Processing Units (GPU). Among these algorithms, the Firefly Algorithm (FA) is a recent proposed metaheuristic that may be used for variable selection. This paper presents a GPU-based FA (FA-MLR) with multiobjective formulation for variable selection in multivariate calibration problems and compares it with some traditional sequential algorithms in the literature. The advantage of the proposed implementation is demonstrated in an example involving a relatively large number of variables. The results showed that the FA-MLR, in comparison with the traditional algorithms is a more suitable choice and a relevant contribution for the variable selection problem. Additionally, the results also demonstrated that the FA-MLR performed in a GPU can be five times faster than its sequential implementation.

Determination of ambroxol hydrochloride, methylparaben and benzoic acid in pharmaceutical preparations based on sequential injection technique coupled with monolithic column.

PubMed

Satínský, Dalibor; Huclová, Jitka; Ferreira, Raquel L C; Montenegro, Maria Conceição B S M; Solich, Petr

2006-02-13

The porous monolithic columns show high performance at relatively low pressure. The coupling of short monoliths with sequential injection technique (SIA) results in a new approach to implementation of separation step to non-separation low-pressure method. In this contribution, a new separation method for simultaneous determination of ambroxol, methylparaben and benzoic acid was developed based on a novel reversed-phase sequential injection chromatography (SIC) technique with UV detection. A Chromolith SpeedROD RP-18e, 50-4.6 mm column with 10 mm precolumn and a FIAlab 3000 system with a six-port selection valve and 5 ml syringe were used for sequential injection chromatographic separations in our study. The mobile phase used was acetonitrile-tetrahydrofuran-0.05M acetic acid (10:10:90, v/v/v), pH 3.75 adjusted with triethylamine, flow rate 0.48 mlmin(-1), UV-detection was at 245 nm. The analysis time was <11 min. A new SIC method was validated and compared with HPLC. The method was found to be useful for the routine analysis of the active compounds ambroxol and preservatives (methylparaben or benzoic acid) in various pharmaceutical syrups and drops.

Sequential EMT-MET induces neuronal conversion through Sox2

PubMed Central

He, Songwei; Chen, Jinlong; Zhang, Yixin; Zhang, Mengdan; Yang, Xiao; Li, Yuan; Sun, Hao; Lin, Lilong; Fan, Ke; Liang, Lining; Feng, Chengqian; Wang, Fuhui; Zhang, Xiao; Guo, Yiping; Pei, Duanqing; Zheng, Hui

2017-01-01

Direct neuronal conversion can be achieved with combinations of small-molecule compounds and growth factors. Here, by studying the first or induction phase of the neuronal conversion induced by defined 5C medium, we show that the Sox2-mediated switch from early epithelial–mesenchymal transition (EMT) to late mesenchymal–epithelial transition (MET) within a high proliferation context is essential and sufficient for the conversion from mouse embryonic fibroblasts (MEFs) to TuJ+ cells. At the early stage, insulin and basic fibroblast growth factor (bFGF)-induced cell proliferation, early EMT, the up-regulation of Stat3 and Sox2, and the subsequent activation of neuron projection. Up-regulated Sox2 then induced MET and directed cells towards a neuronal fate at the late stage. Inhibiting either stage of this sequential EMT-MET impaired the conversion. In addition, Sox2 could replace sequential EMT-MET to induce a similar conversion within a high proliferation context, and its functions were confirmed with other neuronal conversion protocols and MEFs reprogramming. Therefore, the critical roles of the sequential EMT-MET were implicated in direct cell fate conversion in addition to reprogramming, embryonic development and cancer progression. PMID:28580167

Health Care Provider Physical Activity Prescription Intervention

ERIC Educational Resources Information Center

Josyula, Lakshmi; Lyle, Roseann

2013-01-01

Purpose: To examine the feasibility and impact of a health care provider’s (HCP) physical activity (PA) prescription on the PA of patients on preventive care visits. Methods: Consenting adult patients completed health and PA questionnaires and were sequentially assigned to intervention groups. HCPs prescribed PA using a written prescription only…

Mothers' Knowledge of Early Adolescents' Activities following the Middle School Transition and Pubertal Maturation

ERIC Educational Resources Information Center

Laird, Robert D.; Marrero, Matthew D.

2011-01-01

This study tested a sequential mediation model to determine whether experiences, social cognitions, or parent-adolescent interactional processes account for lower levels of mothers' knowledge of adolescents' whereabouts and activities following early adolescents' transition into middle school (MS) and pubertal development. Cross-sectional data…

Energy Conservation Activity Guide, Grades 9-12. Bulletin 1602.

ERIC Educational Resources Information Center

Fraser, Mollie; And Others

As an interdisciplinary, non-sequential teaching guide, this publication was developed to increase awareness and understanding of the energy situation and to encourage individuals to become energy conservationists. Sections provide background information for the teacher followed by a variety of student activities using different subject areas for…

READINESS AND READING FOR THE RETARDED CHILD.

ERIC Educational Resources Information Center

BERNSTEIN, BEBE

THIS TEACHER'S BOOK AND MANUAL, DESIGNED TO ACCOMPANY TWO WORKBOOKS, PRESENTS A FUNCTIONAL APPROACH TO READINESS AND READING FOR YOUNG EDUCABLE RETARDED CHILDREN. THE WORKBOOKS THEMSELVES OFFER PREPARATORY ACTIVITIES FOR CHILDREN AT THE READINESS LEVEL AND SEQUENTIAL ACTIVITIES AND MATERIALS FOR THOSE AT THE BEGINNING READING STAGE. THE TEACHER'S…

Mathemagenic Activities Program: [Reports on Cognitive/Language Development].

ERIC Educational Resources Information Center

Smock, Charles D., Ed.

This set of 13 research reports, bulletins and papers is a product of the Mathemagenic Activities Program (MAP) for early childhood education of the University of Georgia Follow Through Program. Based on Piagetian theory, the MAP provides sequentially structured sets of curriculum materials and processes that are designed to continually challenge…

A Computational Model of Event Segmentation from Perceptual Prediction

ERIC Educational Resources Information Center

Reynolds, Jeremy R.; Zacks, Jeffrey M.; Braver, Todd S.

2007-01-01

People tend to perceive ongoing continuous activity as series of discrete events. This partitioning of continuous activity may occur, in part, because events correspond to dynamic patterns that have recurred across different contexts. Recurring patterns may lead to reliable sequential dependencies in observers' experiences, which then can be used…

Rac Regulates Giardia lamblia Encystation by Coordinating Cyst Wall Protein Trafficking and Secretion.

PubMed

Krtková, Jana; Thomas, Elizabeth B; Alas, Germain C M; Schraner, Elisabeth M; Behjatnia, Habib R; Hehl, Adrian B; Paredez, Alexander R

2016-08-23

Encystation of the common intestinal parasite Giardia lamblia involves the production, trafficking, and secretion of cyst wall material (CWM). However, the molecular mechanism responsible for the regulation of these sequential processes remains elusive. Here, we examined the role of GlRac, Giardia's sole Rho family GTPase, in the regulation of endomembrane organization and cyst wall protein (CWP) trafficking. Localization studies indicated that GlRac is associated with the endoplasmic reticulum (ER) and the Golgi apparatus-like encystation-specific vesicles (ESVs). Constitutive GlRac signaling increased levels of the ER marker PDI2, induced ER swelling, reduced overall CWP1 production, and promoted the early maturation of ESVs. Quantitative analysis of cells expressing constitutively active hemagglutinin (HA)-tagged GlRac (HA-Rac(CA)) revealed fewer but larger ESVs than control cells. Consistent with the phenotype of premature maturation of ESVs in HA-Rac(CA)-expressing cells, constitutive GlRac signaling resulted in increased CWP1 secretion and, conversely, morpholino depletion of GlRac blocked CWP1 secretion. Wild-type cells unexpectedly secreted large quantities of CWP1 into the medium, and free CWP1 was used cooperatively during cyst formation. These results, in part, could account for the previously reported observation that G. lamblia encysts more efficiently at high cell densities. These studies of GlRac show that it regulates encystation at several levels, and our findings support its coordinating role as a regulator of CWP trafficking and secretion. The central role of GlRac in regulating membrane trafficking and the cytoskeleton, both of which are essential to Giardia parasitism, further suggests its potential as a novel target for drug development to treat giardiasis. The encystation process is crucial for the transmission of giardiasis and the life cycle of many protists. Encystation for Giardia lamblia involves the assembly of a protective cyst wall via sequential production, trafficking, and secretion of cyst wall material. However, the regulatory pathways that coordinate cargo maturation and secretion remain unknown. Here, we asked whether the signaling activities of G. lamblia's single Rho family GTPase, GlRac, might have a regulatory role in the encystation process. We show that GlRac localizes to endomembranes and its signaling activities regulate the production of cyst wall protein 1 (CWP1), the maturation of encystation-specific vesicles (ESVs), and secretion of CWP1. We also show that secreted CWP1 is available for the development of cysts at the population level, a finding that in part could explain why Giardia encystation proceeds more efficiently at high cell densities. Copyright © 2016 Krtková et al.

Relevance of the Axis Spermidine/eIF5A for Plant Growth and Development

PubMed Central

Belda-Palazón, Borja; Almendáriz, Carla; Martí, Esmeralda; Carbonell, Juan; Ferrando, Alejandro

2016-01-01

One key role of the essential polyamine spermidine in eukaryotes is to provide the 4-aminobutyl moiety group destined to the post-translational modification of a lysine in the highly conserved translation factor eIF5A. This modification is catalyzed by two sequential enzymatic steps leading to the activation of eIF5A by the conversion of one conserved lysine to the unusual amino acid hypusine. The active translation factor facilitates the sequence-specific translation of polyproline sequences that otherwise cause ribosome stalling. In spite of the well-characterized involvement of active eIF5A in the translation of proline repeat-rich proteins, its biological role has been recently elucidated only in mammals, and it is poorly described at the functional level in plants. Here we describe the alterations in plant growth and development caused by RNAi-mediated conditional genetic inactivation of the hypusination pathway in Arabidopsis thaliana by knocking-down the enzyme deoxyhypusine synthase. We have uncovered that spermidine-mediated activation of eIF5A by hypusination is involved in several aspects of plant biology such as the control of flowering time, the aerial and root architecture, and root hair growth. In addition this pathway is required for adaptation to challenging growth conditions such as high salt and high glucose medium and to elevated concentrations of the plant hormone ABA. We have also performed a bioinformatic analysis of polyproline-rich containing proteins as putative eIF5A targets to uncover their organization in clusters of protein networks to find molecular culprits for the disclosed phenotypes. This study represents a first attempt to provide a holistic view of the biological relevance of the spermidine-dependent hypusination pathway for plant growth and development. PMID:26973686

RETRACTED: Aerobic degradation of 4-nitroaniline (4-NA) via novel degradation intermediates by Rhodococcus sp. strain FK48.

PubMed

Khan, Fazlurrahman; Pandey, Janmejay; Vikram, Surendra; Pal, Deepika; Cameotra, Swaranjit Singh

2013-06-15

An aerobic strain, Rhodococcus sp. strain FK48, capable of growing on 4-nitroaniline (4-NA) as the sole source of carbon, nitrogen, and energy has been isolated from enrichment cultures originating from contaminated soil samples. During growth studies with non- induced cells of FK48 catalyzed sequential denitrification (release of NO₂ substituent) and deamination (release of NH₂ substituent) of 4-NA. However, none of the degradation intermediates could be identified with growth studies. During resting cell studies, 4-NA-induced cells of strain FK48 transformed 4-NA via a previously unknown pathway which involved oxidative hydroxylation leading to formation of 4-aminophenol (4-AP). Subsequent degradation involved oxidated deamination of 4-AP and formation of 1,2,4-benzenetriol (BT) as the major identified terminal aromatic intermediate. Identification of these intermediates was ascertained by HPLC, and GC-MS analyses of the culture supernatants. 4-NA-induced cells of strain FK48 showed positive activity for 1,2,4-benzenetriol dioxygenase in spectrophotometric assay. This is the first conclusive study on aerobic microbial degradation of 4-NA and elucidation of corresponding metabolic pathway. Copyright © 2013 Elsevier B.V. All rights reserved.

Information Foraging for Perceptual Decisions

PubMed Central

2016-01-01

We tested an information foraging framework to characterize the mechanisms that drive active (visual) sampling behavior in decision problems that involve multiple sources of information. Experiments 1 through 3 involved participants making an absolute judgment about the direction of motion of a single random dot motion pattern. In Experiment 4, participants made a relative comparison between 2 motion patterns that could only be sampled sequentially. Our results show that: (a) Information (about noisy motion information) grows to an asymptotic level that depends on the quality of the information source; (b) The limited growth is attributable to unequal weighting of the incoming sensory evidence, with early samples being weighted more heavily; (c) Little information is lost once a new source of information is being sampled; and (d) The point at which the observer switches from 1 source to another is governed by online monitoring of his or her degree of (un)certainty about the sampled source. These findings demonstrate that the sampling strategy in perceptual decision-making is under some direct control by ongoing cognitive processing. More specifically, participants are able to track a measure of (un)certainty and use this information to guide their sampling behavior. PMID:27819455

[Exercise therapy as a therapeutic concept].

PubMed

Reer, R; Ziegler, M; Braumann, K-M

2005-08-01

Lack of exercise is a primary cause for today's level of morbidity and mortality in the Western world. Thus, exercise as a therapeutic modality has an important role. Beneficial effects of exercise have been extensively documented, specifically in primary and secondary prevention of coronary heart disease (CHD), diabetes mellitus, hypertension, disorders of fat metabolism, heart insufficiency, cancer, etc. A regular (at least 3 x per week) endurance training program of 30-40 min duration at an intensity of 65-70% of VO(2)max involving large muscle groups is recommended. The specific exercise activity can also positively affect individuals with orthopedic disease patterns, i.e., osteoporosis, back pain, postoperative rehabilitation, etc. Endurance strength training in the form of sequential training involving approx. 8-10 different exercises for the most important muscle groups 2 x per week is a suitable exercise therapy. One to three sets with 8-12 repetitions per exercise should be performed until volitional exhaustion of the trained muscle groups among healthy adults and 15-20 repetitions among older and cardiac patients. Apart from a positive effect on the locomotor system, this type of strength training has positive effects on CHD, diabetes mellitus, and cancer.

Purification and characterization of the enzymes involved in nicotinamide adenine dinucleotide degradation by Penicillium brevicompactum NRC 829.

PubMed

Ali, Thanaa Hamed; El-Ghonemy, Dina Helmy

2016-06-01

The present study was conducted to investigate a new pathway for the degradation of nicotinamide adenine dinucleotide (NAD) by Penicillium brevicompactum NRC 829 extracts. Enzymes involved in the hydrolysis of NAD, i.e. alkaline phosphatase, aminohydrolase and glycohydrolase were determined. Alkaline phosphatase was found to catalyse the sequential hydrolysis of two phosphate moieties of NAD molecule to nicotinamide riboside plus adenosine. Adenosine was then deaminated by aminohydrolase to inosine and ammonia. While glycohydrolase catalyzed the hydrolysis of the nicotinamide-ribosidic bond of NAD+ to produce nicotinamide and ADP-ribose in equimolar amounts, enzyme purification through a 3-step purification procedure revealed the existence of two peaks of alkaline phosphatases, and one peak contained deaminase and glycohydrolase activities. NAD deaminase was purified to homogeneity as estimated by sodium dodecyl sulphate-polyacrylamide gel electrophoresis with an apparent molecular mass of 91 kDa. Characterization and determination of some of NAD aminohydrolase kinetic properties were conducted due to its biological role in the regulation of cellular NAD level. The results also revealed that NAD did not exert its feedback control on nicotinamide amidase produced by P. brevicompactum.

What happens during annual appraisal interviews? How leader-follower interactions unfold and impact interview outcomes.

PubMed

Meinecke, Annika L; Lehmann-Willenbrock, Nale; Kauffeld, Simone

2017-07-01

Despite a wealth of research on antecedents and outcomes of annual appraisal interviews, the ingredients that make for a successful communication process within the interview itself remain unclear. This study takes a communication approach to highlight leader-follower dynamics in annual appraisal interviews. We integrate relational leadership theory and recent findings on leader-follower interactions to argue (a) how supervisors' task- and relation-oriented statements can elicit employee involvement during the interview process and (b) how these communication patterns affect both supervisors' and employees' perceptions of the interview. Moreover, we explore (c) how supervisor behavior is contingent upon employee contributions to the appraisal interview. We audiotaped 48 actual annual appraisal interviews between supervisors and their employees. Adopting a multimethod approach, we used quantitative interaction coding (N = 32,791 behavioral events) as well as qualitative open-axial coding to explore communication patterns among supervisors and their employees. Lag sequential analysis revealed that supervisors' relation-oriented statements triggered active employee contributions and vice versa. These relation-activation patterns were linked to higher interview success ratings by both supervisors and employees. Moreover, our qualitative findings highlight employee disagreement as a crucial form of active employee contributions during appraisal interviews. We distinguish what employees disagreed about, how the disagreement was enacted, and how supervisors responded to it. Overall employee disagreement was negatively related to ratings of supervisor support. We discuss theoretical implications for performance appraisal and leadership theory and derive practical recommendations for promoting employee involvement during appraisal interviews. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Using Covert Response Activation to Test Latent Assumptions of Formal Decision-Making Models in Humans.

PubMed

Servant, Mathieu; White, Corey; Montagnini, Anna; Burle, Borís

2015-07-15

Most decisions that we make build upon multiple streams of sensory evidence and control mechanisms are needed to filter out irrelevant information. Sequential sampling models of perceptual decision making have recently been enriched by attentional mechanisms that weight sensory evidence in a dynamic and goal-directed way. However, the framework retains the longstanding hypothesis that motor activity is engaged only once a decision threshold is reached. To probe latent assumptions of these models, neurophysiological indices are needed. Therefore, we collected behavioral and EMG data in the flanker task, a standard paradigm to investigate decisions about relevance. Although the models captured response time distributions and accuracy data, EMG analyses of response agonist muscles challenged the assumption of independence between decision and motor processes. Those analyses revealed covert incorrect EMG activity ("partial error") in a fraction of trials in which the correct response was finally given, providing intermediate states of evidence accumulation and response activation at the single-trial level. We extended the models by allowing motor activity to occur before a commitment to a choice and demonstrated that the proposed framework captured the rate, latency, and EMG surface of partial errors, along with the speed of the correction process. In return, EMG data provided strong constraints to discriminate between competing models that made similar behavioral predictions. Our study opens new theoretical and methodological avenues for understanding the links among decision making, cognitive control, and motor execution in humans. Sequential sampling models of perceptual decision making assume that sensory information is accumulated until a criterion quantity of evidence is obtained, from where the decision terminates in a choice and motor activity is engaged. The very existence of covert incorrect EMG activity ("partial error") during the evidence accumulation process challenges this longstanding assumption. In the present work, we use partial errors to better constrain sequential sampling models at the single-trial level. Copyright © 2015 the authors 0270-6474/15/3510371-15$15.00/0.

Investigating Streams and Rivers. An Interdisciplinary Curriculum Guide for Use with Mitchell and Stapp's "Field Manual for Water Quality Monitoring."

ERIC Educational Resources Information Center

Cromwell, Mare; And Others

This guide contains 12 activities designed to encourage secondary school student inquiry, investigation, and action regarding local streams and rivers. The activities are sequential and organized into three topic areas. The first section consists of three activities that help orient students to their local watercourse. Students map a local…

Language Non-Selective Activation of Orthography during Spoken Word Processing in Hindi-English Sequential Bilinguals: An Eye Tracking Visual World Study

ERIC Educational Resources Information Center

Mishra, Ramesh Kumar; Singh, Niharika

2014-01-01

Previous psycholinguistic studies have shown that bilinguals activate lexical items of both the languages during auditory and visual word processing. In this study we examined if Hindi-English bilinguals activate the orthographic forms of phonological neighbors of translation equivalents of the non target language while listening to words either…

Mystery Boxes, X Rays, and Radiology.

ERIC Educational Resources Information Center

Thomson, Norman

2000-01-01

Indicates the difficulties of teaching concepts beyond light and color and creating memorable learning experiences. Recommends sequential activities using the mystery box approach to explain how scientists and doctors use photon applications. (YDS)