Dynamic flashing yellow arrow (FYA) : a study on variable left turn mode operational and safety impacts.

DOT National Transportation Integrated Search

2013-12-01

Accommodating left turns at signalized intersections has been a challenge for traffic engineers as they : seek balance between two conflicting goals; capacity and safety. The use of a four-section head for the left-turn : lane only with a flashing ye...

Deciding alternative left turn signal phases using expert systems

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

Chang, E.C.P.

1988-01-01

The Texas Transportation Institute (TTI) conducted a study to investigate the feasibility of applying artificial intelligence (AI) technology and expert systems (ES) design concepts to a traffic engineering problem. Prototype systems were developed to analyze user input, evaluate various reasoning, and suggest suitable left turn phase treatment. These systems were developed using AI programming tools on IBM PC/XT/AT-compatible microcomputers. Two slightly different systems were designed using AI languages; another was built with a knowledge engineering tool. These systems include the PD PROLOG and TURBO PROLOG AI programs, as well as the INSIGHT Production Rule Language.

Operational evaluation of right turns followed by U-turns as an alternative to direct left turns, Vol. 3

DOT National Transportation Integrated Search

2001-09-01

This project evaluated the safety and operational impacts of two alternative left-turn treatments from driveways/side streets. The two treatments were: (1) Direct left turns (DLT) and, (2) Right turns followed by U-turns (RTUT). Ten sites were select...

Safety evaluation of right turns followed by U-turns as an alternative to direct left turns : conflict analysis, Vol. 2

DOT National Transportation Integrated Search

2001-10-01

This project evaluated the safety and operational impacts of two alternative left-turn treatments from driveways/side streets. The two treatments were (1) direct left turns and (2) right turns followed by U-turns. Safety analyses of the alternatives ...

Safety evaluation of intersections with dynamic use of exit-lanes for left-turn using field data.

PubMed

Zhao, Jing; Liu, Yue

2017-05-01

As a newly proposed unconventional intersection design, the exit-lanes for left-turn (EFL) intersection is found to be effective in increasing the intersection capacity with high level of application flexibility, especially under heavy left-turn traffic conditions. However, the operational safety of EFL is of most concern to the authority prior to its implementation. This paper evaluates the safety of the EFL intersections by studying the behavior of left-turn maneuvers using field data collected at 7 locations in China. A total of 22830 left-turn vehicles were captured, in which 9793 vehicles turned left using the mixed-usage area. Four potential safety problems, including the red-light violations, head-on collision risks, trapped vehicles, and rear-end crash risks, were discussed. Statistical analyses were carried out to compare the safety risk between the EFL intersection and the conventional one. Results indicate that the safety problems of EFL intersections mainly lie in higher percentages in red-light violations at the pre-signal (1.83% higher), wrong-way violation problems during the peak hours (the violation rate reaches up to 11.07%), and the lower travel speeds in the mixed-usage area (18.75% lower). Such risks can be counteracted, however, by providing more guiding information, installing cameras to investigate and punish violation maneuvers, and adjusting design parameter values for layout design and signal timing, respectively. Copyright © 2017 Elsevier Ltd. All rights reserved.

Safety evaluation of right turns followed by U-turns as an alternative to direct left turns : crash data analysis, Vol. 1

DOT National Transportation Integrated Search

2001-10-01

This project evaluated the safety and operational impacts of two alternative left-turn treatments from driveway/side streets. The two treatments were: (1) direct left turns and, (2) right turns followed by U-turns. Safety analyses of the alternatives...

Guidelines for the use of no U-turn and no left-turn signs.

DOT National Transportation Integrated Search

1994-01-01

The objective of this study was to establish a set of written guidelines identifying traffic and road conditions where No U-Turn and No Left Turn signs should be installed. The effect of these signs on traffic safety was also investigated. A question...

Displaced left turn intersection : informational guide.

DOT National Transportation Integrated Search

2014-08-01

This document provides information and guidance on the Displaced Left Turn (DLT) intersection. To the extent possible, the : guide addresses a variety of conditions found in the United States, to achieve designs suitable for a wide array of potential...

Development of guidelines for triple left and dual right-turn lanes : technical report.

DOT National Transportation Integrated Search

2011-07-01

Left- or right-turn lanes at intersections improve safety and operations by separating turning and through vehicles. At intersections : with heavy turning demand, it may be necessary to provide multiple turn lanes. Triple left-turn (TLT) and dual rig...

Childrens' left-turning preference is not modulated by magical ideation.

PubMed

Streuli, Jürg C; Obrist, Gina; Brugger, Peter

2017-01-01

The literature on human turning preferences is inconsistent. While the few studies with children below 14 years of age uniformly describe an overall left-turning (counterclockwise) tendency, a recent Internet study with more than 1500 adults found a right-sided (clockwise) bias. We set out to investigate spontaneous turning behaviour in children age 5-3 years and, based on neuropsychiatric work in adults, also explored a potential association with magical thinking. Findings indicated a clear left-turning preference, independent of a participant's sex and handedness. Whether a child responded a question about the existence of extrasensory communication in the affirmative or not was unrelated to direction and size of turning bias and lateral preference. Our results are consistent with a left-sided turning preference reported for children, but in opposition to the clockwise bias recently described in a large-scale study with adults. Whether they point to a maturational gradient in the preferred direction of spontaneous whole-body rotation or rather to a lack of comparability between measures used in observational versus Internet-based studies remains to be further investigated. Regarding a purported association between body turns and magical thinking, our study is preliminary, as only one single question was used to probe the latter.

Driving simulator evaluation of drivers' response to intersections with dynamic use of exit-lanes for left-turn.

PubMed

Zhao, Jing; Yun, Meiping; Zhang, H Michael; Yang, Xiaoguang

2015-08-01

With the worsening of urban traffic congestion in large cities around the world, researchers have been looking for unconventional designs and/or controls to squeeze more capacity out of intersections, the most common bottlenecks of the road network. One of these innovative intersection designs, known as the exit-lanes for left-turn (EFL), opens up exit-lanes to be used by left-turn traffic with the help of an additional traffic light installed at the median opening (the pre-signal). This paper studies how drivers respond to EFL intersections with a series of driving simulator experiments. In our experiments, 64 drivers were recruited and divided into two groups. One group is trained to use the EFL while the other group is not. In addition, four scenarios were considered with different sign and marking designs and traffic conditions in the experiments. Results indicate that drivers show certain amount of confusion and hesitation when encountering an EFL intersection for the first time. They can be overcome, however, by increasing exposure through driver education or by cue provided from other vehicles. Moreover, drivers unfamiliar with EFL operation can make a left turn using the conventional left-turn lanes as usual. The EFL operation is not likely to pose any serious safety risk of the intersection in real life operations. Copyright © 2015 Elsevier Ltd. All rights reserved.

Thunderstorm-scale variations of echoes associated with left-turn tornado families

NASA Technical Reports Server (NTRS)

Forbes, G. S.

1977-01-01

The origin of tornadoes is studied on the basis of changing radar echo shapes and tornado location relative to the echoes. Three types of tornadoes appear to be associated with different hook echo configurations. No-turn or right-turn tornadoes are linked to a steady hook which does not change shape or orientation. Left-turn tornado families are generated in cases where the hook is unsteady and changes orientation at each successive tornado birth. Finally, left-turn tornado families may also be formed when the hook undergoes no orientation change and the tornadoes move along the rear of the hook. The correlation between a thunderstorm-scale cycle and periodic tornado production is also discussed.

Micro-simulation of vehicle conflicts involving right-turn vehicles at signalized intersections based on cellular automata.

PubMed

Chai, C; Wong, Y D

2014-02-01

At intersection, vehicles coming from different directions conflict with each other. Improper geometric design and signal settings at signalized intersection will increase occurrence of conflicts between road users and results in a reduction of the safety level. This study established a cellular automata (CA) model to simulate vehicular interactions involving right-turn vehicles (as similar to left-turn vehicles in US). Through various simulation scenarios for four case cross-intersections, the relationships between conflict occurrences involving right-turn vehicles with traffic volume and right-turn movement control strategies are analyzed. Impacts of traffic volume, permissive right-turn compared to red-amber-green (RAG) arrow, shared straight-through and right-turn lane as well as signal setting are estimated from simulation results. The simulation model is found to be able to provide reasonable assessment of conflicts through comparison of existed simulation approach and observed accidents. Through the proposed approach, prediction models for occurrences and severity of vehicle conflicts can be developed for various geometric layouts and traffic control strategies. Copyright © 2013 Elsevier Ltd. All rights reserved.

Development of guidelines for permitted left-turn phasing using flashing yellow arrows : final report.

DOT National Transportation Integrated Search

2015-06-01

The objective of this project was to develop guidelines for time-of-day use of permitted left-turn phasing, : which can then be implemented using flashing yellow arrows (FYA). This required determining how the risk : for left-turn crashes varied as t...

Dynamic flashing yellow arrow (FYA): a study on variable left-turn mode operational and safety impacts phase II - model expansion and testing.

DOT National Transportation Integrated Search

2016-06-01

The flashing yellow arrow (FYA) signal display creates an opportunity to enhance the left-turn phase with a : variable mode that can be changed on demand. The previously developed decision support system (DSS) in : phase I facilitated the selection o...

The influence of rear turn-signal characteristics on crash risk.

PubMed

Sullivan, John M; Flannagan, Michael J

2012-02-01

The relationship between the relative risk of a rear-end collision during a turn, merge, or lane change maneuver and the characteristics of the rear turn-signal configuration was examined using crash data from seven states in the United States. Rear turn-signal characteristics-including color, optics, separation, and light source-were identified for 55 vehicle models and used in a logistic regression analysis to model the odds of a rear-end collision. Additional variables including driver demographics (gender, age), vehicle age, and light condition were also modeled. Risk was assessed using a contrast group of striking vehicles in similar collisions. The results suggest that the odds of being the struck vehicle were 3% to 28% lower among vehicles equipped with amber versus red turn signals. Although the analysis suggests that there may be a safety benefit associated with amber rear turn signals, it is unclear whether turn-signal color alone is responsible. The results suggest that aspects of a vehicle's rear signal characteristics may influence crash risk. Copyright © 2012 Elsevier Ltd. All rights reserved.

U-Turns at signalized intersections.

DOT National Transportation Integrated Search

2004-06-01

The objectives of the study were to examine the safety consequences from the installation of U-turns at signalized intersections in Kentucky and to develop a set of guidelines for using this alternative in the future. The literature review indicated ...

Coronary sinus signal amplitude predicts left atrial scarring.

PubMed

Attanasio, Philipp; Qaiyumi, Daniel; Röhle, Robert; Wutzler, Alexander; Safak, Erdal; Muntean, Bogdan; Boldt, Leif-Hendrik; Pieske, Burkert; Haverkamp, Wilhelm; Huemer, Martin

2017-12-22

Left atrial scarring is recognised as a critical component in the maintenance of atrial fibrillation and is associated with the failure of interventional treatment. Diminished bipolar voltage (LV) has been proposed as a useful tool for left atrial scar quantification. We hypothesised that, due to its anatomic location, signals on the coronary sinus catheter might be used to predict the amount of left atrial low voltage. A total of 124 patients (42% women, average age 66 ± 9 years) were included. Forty-one with paroxysmal and 83 with persistent atrial fibrillation. Left atrial low-voltage (<0.5 mV, measured during sinus rhythm) area size and distribution varied considerably among the included patients (mean: 34.9%; maximum: 94.6%; minimum: 0.4%). Spearman correlation revealed a strong negative correlation between bipolar voltage of the signals on the coronary sinus catheter and the amount of left atrial scarring (R = -0.778, p < .0001). The optimal CS voltage cut off for prediction of left atrial low-voltage size of ≥50% was 1.9 mV with an area-under-the receiver-operating-characteristic (ROC) curve of 0.982, a sensitivity of 97% and a specificity of 98%. There is a strong negative correlation between the size of left atrial low-voltage areas (LVA) and coronary sinus signal amplitude. With increasing left atrial LVA size, CS signal amplitudes decrease, and vice versa. On the basis of these findings, average CS signal amplitudes of ≤1.9 mV can be used as a predictor for a left atrial low-voltage size of ≥50%.

Revised Planning Methodology For Signalized Intersections And Operational Analysis Of Exclusive Left-Turn Lanes, A Simulation-Based Method, Part - I: Literature Review (Final Report)

DOT National Transportation Integrated Search

1996-04-01

THE STUDY INVESTIGATES THE APPLICATION OF SIMULATION ALONG WITH FIELD OBSERVATIONS FOR ESTIMATION OF EXCLUSIVE LEFT-TURN SATURATION FLOW RATE AND CAPACITY. THE ENTIRE RESEARCH HAS COVERED THE FOLLOWING PRINCIPAL SUBJECTS: (1) A SATURATION FLOW MODEL ...

Effects of turning and through lane sharing on traffic performance at intersections

NASA Astrophysics Data System (ADS)

Li, Xiang; Sun, Jian-Qiao

2016-02-01

Turning vehicles strongly influence traffic flows at intersections. Effective regulation of turning vehicles is important to achieve better traffic performance. This paper studies the impact of lane sharing and turning signals on traffic performance at intersections by using cellular automata. Both right-turn and left-turn lane sharing are studied. Interactions between vehicles and pedestrians are considered. The transportation efficiency, road safety and energy economy are the traffic performance metrics. Extensive simulations are carried out to study the traffic performance indices. It is observed that shared turning lanes and permissive left-turn signal improve the transportation efficiency and reduce the fuel consumption in most cases, but the safety is usually sacrificed. It is not always beneficial for the through vehicles when they are allowed to be in the turning lanes.

No turning, a mouse mutation causing left-right and axial patterning defects.

PubMed

Melloy, P G; Ewart, J L; Cohen, M F; Desmond, M E; Kuehn, M R; Lo, C W

1998-01-01

Patterning along the left/right axes helps establish the orientation of visceral organ asymmetries, a process which is of fundamental importance to the viability of an organism. A linkage between left/right and axial patterning is indicated by the finding that a number of genes involved in left/right patterning also play a role in anteroposterior and dorsoventral patterning. We have recovered a spontaneous mouse mutation causing left/right patterning defects together with defects in anteroposterior and dorsoventral patterning. This mutation is recessive lethal and was named no turning (nt) because the mutant embryos fail to undergo embryonic turning. nt embryos exhibit cranial neural tube closure defects and malformed somites and are caudally truncated. Development of the heart arrests at the looped heart tube stage, with cardiovascular defects indicated by ballooning of the pericardial sac and the pooling of blood in various regions of the embryo. Interestingly, in nt embryos, the direction of heart looping was randomized. Nodal and lefty, two genes that are normally expressed only in the left lateral plate mesoderm, show expression in the right and left lateral plate mesoderm. Lefty, which is normally also expressed in the floorplate, is not found in the prospective floor plate of nt embryos. This suggests the possibility of notochordal defects. This was confirmed by histological analysis and the examination of sonic hedgehog, Brachyury, and HNF-3 beta gene expression. These studies showed that the notochord is present in the early nt embryo, but degenerates as development progresses. Overall, these findings support the hypothesis that the notochord plays an active role in left/right patterning. Our results suggest that nt may participate in this process by modulating the notochordal expression of HNF-3 beta.

Exposure to lateral collision in signalized intersections with protected left turn under different traffic control strategies.

PubMed

Midenet, Sophie; Saunier, Nicolas; Boillot, Florence

2011-11-01

This paper proposes an original definition of the exposure to lateral collision in signalized intersections and discusses the results of a real world experiment. This exposure is defined as the duration of situations where the stream that is given the right-of-way goes through the conflict zone while road users are waiting in the cross-traffic approach. This measure, obtained from video sensors, makes it possible to compare different operating conditions such as different traffic signal strategies. The data from a real world experiment is used, where the adaptive real-time strategy CRONOS (ContRol Of Networks by Optimization of Switchovers) and a time-plan strategy with vehicle-actuated ranges alternately controlled an isolated intersection near Paris. Hourly samples with similar traffic volumes are compared and the exposure to lateral collision is different in various areas of the intersection and various traffic conditions for the two strategies. The total exposure under peak hour traffic conditions drops by roughly 5 min/h with the CRONOS strategy compared to the time-plan strategy, which occurs mostly on entry streams. The results are analyzed through the decomposition of cycles in phase sequences and recommendations are made for traffic control strategies. Copyright © 2011 Elsevier Ltd. All rights reserved.

Specific β-Turns Precede PPIIL Structures Binding to Allele-Specific HLA-DRβ1* PBRs in Fully-Protective Malaria Vaccine Components

PubMed Central

Bermudez, Adriana; Alba, Martha P.; Vanegas, Magnolia; Patarroyo, Manuel A.; Patarroyo, Manuel E.

2018-01-01

The 3D structural analysis of 62 peptides derived from highly pathogenic Plasmodium falciparum malaria parasite proteins involved in host cell invasion led to finding a striking association between particular β-turn types located in the N-terminal peripheral flanking residue region (preceding the polyproline II left-handed structures fitting into the HLA-DRβ* allele family) and modified immune protection-inducing protein structure induced long-lasting protective immunity. This is the first time association between two different secondary structures associated with a specific immunological function has been described: full, long-lasting protective immunity. PMID:29682500

Specific β-Turns Precede PPIIL Structures Binding to Allele-Specific HLA-DRβ1* PBRs in Fully-Protective Malaria Vaccine Components.

PubMed

Bermudez, Adriana; Alba, Martha P; Vanegas, Magnolia; Patarroyo, Manuel A; Patarroyo, Manuel E

2018-01-01

The 3D structural analysis of 62 peptides derived from highly pathogenic Plasmodium falciparum malaria parasite proteins involved in host cell invasion led to finding a striking association between particular β-turn types located in the N-terminal peripheral flanking residue region (preceding the polyproline II left-handed structures fitting into the HLA-DRβ * allele family) and modified i mmune protection-inducing protein structure induced long-lasting protective immunity. This is the first time association between two different secondary structures associated with a specific immunological function has been described: full, long-lasting protective immunity.

Specific β-turns precede PPIIL structures binding to allele-specific HLA-DRβ1* PBRs in fully-protective malaria vaccine components

NASA Astrophysics Data System (ADS)

Bermudez, Adriana; Alba, Martha P.; Vanegas, Magnolia; Patarroyo, Manuel A.; Patarroyo, Manuel E.

2018-04-01

The 3D structural analysis of 62 peptides derived from highly pathogenic Plasmodium falciparum malaria parasite proteins involved in host cell invasion led to finding a striking association between particular β-turn types located in the N-terminal peripheral flanking residue region (preceding the polyproline II left-handed structures fitting into the HLA-DRβ* allele family) and modified immune protection-inducing protein structure induced long-lasting protective immunity. This is the first time association between two different secondary structures associated with a specific immunological function has been described: full, long-lasting protective immunity.

Mirrors in the PDB: left-handed alpha-turns guide design with D-amino acids.

PubMed

Annavarapu, Srinivas; Nanda, Vikas

2009-09-22

Incorporating variable amino acid stereochemistry in molecular design has the potential to improve existing protein stability and create new topologies inaccessible to homochiral molecules. The Protein Data Bank has been a reliable, rich source of information on molecular interactions and their role in protein stability and structure. D-amino acids rarely occur naturally, making it difficult to infer general rules for how they would be tolerated in proteins through an analysis of existing protein structures. However, protein elements containing short left-handed turns and helices turn out to contain useful information. Molecular mechanisms used in proteins to stabilize left-handed elements by L-amino acids are structurally enantiomeric to potential synthetic strategies for stabilizing right-handed elements with D-amino acids. Propensities for amino acids to occur in contiguous alpha(L) helices correlate with published thermodynamic scales for incorporation of D-amino acids into alpha(R) helices. Two backbone rules for terminating a left-handed helix are found: an alpha(R) conformation is disfavored at the amino terminus, and a beta(R) conformation is disfavored at the carboxy terminus. Helix capping sidechain-backbone interactions are found which are unique to alpha(L) helices including an elevated propensity for L-Asn, and L-Thr at the amino terminus and L-Gln, L-Thr and L-Ser at the carboxy terminus. By examining left-handed alpha-turns containing L-amino acids, new interaction motifs for incorporating D-amino acids into right-handed alpha-helices are identified. These will provide a basis for de novo design of novel heterochiral protein folds.

Mirrors in the PDB: left-handed α-turns guide design with D-amino acids

PubMed Central

Annavarapu, Srinivas; Nanda, Vikas

2009-01-01

Background Incorporating variable amino acid stereochemistry in molecular design has the potential to improve existing protein stability and create new topologies inaccessible to homochiral molecules. The Protein Data Bank has been a reliable, rich source of information on molecular interactions and their role in protein stability and structure. D-amino acids rarely occur naturally, making it difficult to infer general rules for how they would be tolerated in proteins through an analysis of existing protein structures. However, protein elements containing short left-handed turns and helices turn out to contain useful information. Molecular mechanisms used in proteins to stabilize left-handed elements by L-amino acids are structurally enantiomeric to potential synthetic strategies for stabilizing right-handed elements with D-amino acids. Results Propensities for amino acids to occur in contiguous αL helices correlate with published thermodynamic scales for incorporation of D-amino acids into αR helices. Two backbone rules for terminating a left-handed helix are found: an αR conformation is disfavored at the amino terminus, and a βR conformation is disfavored at the carboxy terminus. Helix capping sidechain-backbone interactions are found which are unique to αL helices including an elevated propensity for L-Asn, and L-Thr at the amino terminus and L-Gln, L-Thr and L-Ser at the carboxy terminus. Conclusion By examining left-handed α-turns containing L-amino acids, new interaction motifs for incorporating D-amino acids into right-handed α-helices are identified. These will provide a basis for de novo design of novel heterochiral protein folds. PMID:19772623

Cerberus-Nodal-Lefty-Pitx signaling cascade controls left-right asymmetry in amphioxus.

PubMed

Li, Guang; Liu, Xian; Xing, Chaofan; Zhang, Huayang; Shimeld, Sebastian M; Wang, Yiquan

2017-04-04

Many bilaterally symmetrical animals develop genetically programmed left-right asymmetries. In vertebrates, this process is under the control of Nodal signaling, which is restricted to the left side by Nodal antagonists Cerberus and Lefty. Amphioxus, the earliest diverging chordate lineage, has profound left-right asymmetry as a larva. We show that Cerberus , Nodal , Lefty , and their target transcription factor Pitx are sequentially activated in amphioxus embryos. We then address their function by transcription activator-like effector nucleases (TALEN)-based knockout and heat-shock promoter (HSP)-driven overexpression. Knockout of Cerberus leads to ectopic right-sided expression of Nodal , Lefty , and Pitx , whereas overexpression of Cerberus represses their left-sided expression. Overexpression of Nodal in turn represses Cerberus and activates Lefty and Pitx ectopically on the right side. We also show Lefty represses Nodal , whereas Pitx activates Nodal These data combine in a model in which Cerberus determines whether the left-sided gene expression cassette is activated or repressed. These regulatory steps are essential for normal left-right asymmetry to develop, as when they are disrupted embryos may instead form two phenotypic left sides or two phenotypic right sides. Our study shows the regulatory cassette controlling left-right asymmetry was in place in the ancestor of amphioxus and vertebrates. This includes the Nodal inhibitors Cerberus and Lefty, both of which operate in feedback loops with Nodal and combine to establish asymmetric Pitx expression. Cerberus and Lefty are missing from most invertebrate lineages, marking this mechanism as an innovation in the lineage leading to modern chordates.

Evaluation of a Risk Awareness Perception Training Program on Novice Teen Driver Behavior at Left-Turn Intersections.

PubMed

McDonald, Catherine C; Kandadai, Venk; Loeb, Helen; Seacrist, Thomas; Lee, Yi-Ching; Bonfiglio, Dana; Fisher, Donald L; Winston, Flaura K

Collisions at left turn intersections are among the most prevalent types of teen driver serious crashes, with inadequate surveillance as a key factor. Risk awareness perception training (RAPT) has shown effectiveness in improving hazard anticipation for latent hazards. The goal of this study was to determine if RAPT version 3 (RAPT-3) improved intersection turning behaviors among novice teen drivers when the hazards were not latent and frequent glancing to multiple locations at the intersection was needed. Teens aged 16-18 with ≤180 days of licensure were randomly assigned to: 1) an intervention group (n=18) that received RAPT-3 (Trained); or 2) a control group (n=19) that received no training (Untrained). Both groups completed RAPT-3 Baseline Assessment and the Trained group completed RAPT-3 Training and RAPT-3 Post Assessment. Training effects were evaluated on a driving simulator. Simulator ( gap selection errors and collisions ) and eye tracker ( traffic check errors) metrics from six left-turn stop sign controlled intersections in the Simulated Driving Assessment (SDA) were analyzed. The Trained group scored significantly higher in RAPT-3 Post Assessment than RAPT-3 Baseline Assessment (p< 0.0001). There were no significant differences in either traffic check and gap selection errors or collisions among Trained and Untrained teens in the SDA. Though Trained teens learned about hazard anticipation related to latent hazards, learning did not translate to performance differences in left-turn stop sign controlled intersections where the hazards were not latent. Our findings point to further research to better understand the challenges teens have with left turn intersections.

Safety implications of the use of the flashing yellow arrow for permissive left turns.

DOT National Transportation Integrated Search

2011-01-01

The use of the flashing yellow arrow (FYA) for permissive left turns is relatively new to California, with at least five : installations approved under a 2006 Federal Highway Administration (FHWA) Interim Approval memorandum. : Inclusion of formal gu...

The Bmp signaling pathway regulates development of left-right asymmetry in amphioxus.

PubMed

Soukup, Vladimir; Kozmik, Zbynek

2018-02-01

Establishment of asymmetry along the left-right (LR) body axis in vertebrates requires interplay between Nodal and Bmp signaling pathways. In the basal chordate amphioxus, the left-sided activity of the Nodal signaling has been attributed to the asymmetric morphogenesis of paraxial structures and pharyngeal organs, however the role of Bmp signaling in LR asymmetry establishment has not been addressed to date. Here, we show that Bmp signaling is necessary for the development of LR asymmetric morphogenesis of amphioxus larvae through regulation of Nodal signaling. Loss of Bmp signaling results in loss of the left-sided expression of Nodal, Gdf1/3, Lefty and Pitx and in gain of ectopic expression of Cerberus on the left side. As a consequence, the larvae display loss of the offset arrangement of axial structures, loss of the left-sided pharyngeal organs including the mouth, and ectopic development of the right-sided organs on the left side. Bmp inhibition thus phenocopies inhibition of Nodal signaling and results in the right isomerism. We conclude that Bmp and Nodal pathways act in concert to specify the left side and that Bmp signaling plays a fundamental role during LR development in amphioxus. Copyright © 2017 Elsevier Inc. All rights reserved.

32 CFR 935.134 - Arm signals.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 32 National Defense 6 2013-07-01 2013-07-01 false Arm signals. 935.134 Section 935.134 National... WAKE ISLAND CODE Motor Vehicle Code § 935.134 Arm signals. (a) Any person operating a motor vehicle and... signal for a turn or stop is made by fully extending the left arm as follows: (1) Left turn—extend left...

32 CFR 935.134 - Arm signals.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 32 National Defense 6 2012-07-01 2012-07-01 false Arm signals. 935.134 Section 935.134 National... WAKE ISLAND CODE Motor Vehicle Code § 935.134 Arm signals. (a) Any person operating a motor vehicle and... signal for a turn or stop is made by fully extending the left arm as follows: (1) Left turn—extend left...

32 CFR 935.134 - Arm signals.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 32 National Defense 6 2014-07-01 2014-07-01 false Arm signals. 935.134 Section 935.134 National... WAKE ISLAND CODE Motor Vehicle Code § 935.134 Arm signals. (a) Any person operating a motor vehicle and... signal for a turn or stop is made by fully extending the left arm as follows: (1) Left turn—extend left...

AUGMENTED REALITY CUES TO ASSIST OLDER DRIVERS WITH GAP ESTIMATION FOR LEFT-TURNS

PubMed Central

Rusch, Michelle L.; Schall, Mark C.; Lee, John D.; Dawson, Jeffrey D.; Rizzo, Matthew

2014-01-01

The objective of this study was to assess the effects of augmented reality (AR) cues designed to assist middle-aged and older drivers with a range of UFOV impairments, judging when to make left-turns across oncoming traffic. Previous studies have shown that AR cues can help middle-aged and older drivers respond to potential roadside hazards by increasing hazard detection without interfering with other driving tasks. Intersections pose a critical challenge for cognitively impaired drivers, prone to misjudge time-to-contact with oncoming traffic. We investigated whether AR cues improve or interfere with hazard perception in left-turns across oncoming traffic for drivers with age-related cognitive decline. Sixty-four middle-aged and older drivers with a range of UFOV impairment judged when it would be safe to turn left across oncoming traffic approaching the driver from the opposite direction in a rural stop-sign controlled intersection scenario implemented in a static base driving simulator. Outcome measures used to evaluate the effectiveness of AR cueing included: Time-to-Contact (TTC), Gap Time Variation (GTV), Response Rate, and Gap Response Variation (GRV). All drivers estimated TTCs were shorter in cued than in uncued conditions. In addition, drivers responded more often in cued conditions than in uncued conditions and GRV decreased for all drivers in scenarios that contained AR cues. For both TTC and response rate, drivers also appeared to adjust their behavior to be consistent with the cues, especially drivers with the poorest UFOV scores (matching their behavior to be close to middle-aged drivers). Driver ratings indicated that cueing was not considered to be distracting. Further, various conditions of reliability (e.g., 15% miss rate) did not appear to affect performance or driver ratings. PMID:24950128

Augmented reality cues to assist older drivers with gap estimation for left-turns.

PubMed

Rusch, Michelle L; Schall, Mark C; Lee, John D; Dawson, Jeffrey D; Rizzo, Matthew

2014-10-01

The objective of this study was to assess the effects of augmented reality (AR) cues designed to assist middle-aged and older drivers with a range of UFOV impairments, judging when to make left-turns across oncoming traffic. Previous studies have shown that AR cues can help middle-aged and older drivers respond to potential roadside hazards by increasing hazard detection without interfering with other driving tasks. Intersections pose a critical challenge for cognitively impaired drivers, prone to misjudge time-to-contact with oncoming traffic. We investigated whether AR cues improve or interfere with hazard perception in left-turns across oncoming traffic for drivers with age-related cognitive decline. Sixty-four middle-aged and older drivers with a range of UFOV impairment judged when it would be safe to turn left across oncoming traffic approaching the driver from the opposite direction in a rural stop-sign controlled intersection scenario implemented in a static base driving simulator. Outcome measures used to evaluate the effectiveness of AR cueing included: Time-to-Contact (TTC), Gap Time Variation (GTV), Response Rate, and Gap Response Variation (GRV). All drivers estimated TTCs were shorter in cued than in uncued conditions. In addition, drivers responded more often in cued conditions than in uncued conditions and GRV decreased for all drivers in scenarios that contained AR cues. For both TTC and response rate, drivers also appeared to adjust their behavior to be consistent with the cues, especially drivers with the poorest UFOV scores (matching their behavior to be close to middle-aged drivers). Driver ratings indicated that cueing was not considered to be distracting. Further, various conditions of reliability (e.g., 15% miss rate) did not appear to affect performance or driver ratings. Copyright © 2014 Elsevier Ltd. All rights reserved.

Improved pedestrian safety at signalized intersections operating the flashing yellow arrow.

DOT National Transportation Integrated Search

2013-04-01

In some jurisdictions, protected left-turn phasing has been replaced with the flashing yellow arrow (FYA) for : protected/permissive left turns (PPLTs) to reduce delay. However, it is important to have a thorough understanding of the : conflict betwe...

Measurement of signal use and vehicle turns as indication of driver cognition.

PubMed

Wallace, Bruce; Goubran, Rafik; Knoefel, Frank

2014-01-01

This paper uses data analytics to provide a method for the measurement of a key driving task, turn signal usage as a measure of an automatic over-learned cognitive function drivers. The paper augments previously reported more complex executive function cognition measures by proposing an algorithm that analyzes dashboard video to detect turn indicator use with 100% accuracy without any false positives. The paper proposes two algorithms that determine the actual turns made on a trip. The first through analysis of GPS location traces for the vehicle, locating 73% of the turns made with a very low false positive rate of 3%. A second algorithm uses GIS tools to retroactively create turn by turn directions. Fusion of GIS and GPS information raises performance to 77%. The paper presents the algorithm required to measure signal use for actual turns by realigning the 0.2Hz GPS data, 30fps video and GIS turn events. The result is a measure that can be tracked over time and changes in the driver's performance can result in alerts to the driver, caregivers or clinicians as indication of cognitive change. A lack of decline can also be shared as reassurance.

Research on traffic flow characteristics at signal intersection

NASA Astrophysics Data System (ADS)

Zeng, Jun-Wei; Yu, Sen-Bin; Qian, Yong-Sheng; Wei, Xu-Ting; Feng, Xiao; Wang, Hui

2017-09-01

Based on the cautious driving behavior and the principle of the vehicles at left-side having priority to pass in the intersection, a two-dimensional cellular automata model for planar signalized intersection (NS-STCA) is established. The different turning vehicles are regarded as the research objects and the effect of the left-turn probability, signal cycle, vehicle flow density on traffic flow at the intersection is investigated.

Reciprocal Signaling between the Ectoderm and a Mesendodermal Left-Right Organizer Directs Left-Right Determination in the Sea Urchin Embryo

PubMed Central

Bessodes, Nathalie; Haillot, Emmanuel; Duboc, Véronique; Röttinger, Eric; Lahaye, François; Lepage, Thierry

2012-01-01

During echinoderm development, expression of nodal on the right side plays a crucial role in positioning of the rudiment on the left side, but the mechanisms that restrict nodal expression to the right side are not known. Here we show that establishment of left-right asymmetry in the sea urchin embryo relies on reciprocal signaling between the ectoderm and a left-right organizer located in the endomesoderm. FGF/ERK and BMP2/4 signaling are required to initiate nodal expression in this organizer, while Delta/Notch signaling is required to suppress formation of this organizer on the left side of the archenteron. Furthermore, we report that the H+/K+-ATPase is critically required in the Notch signaling pathway upstream of the S3 cleavage of Notch. Our results identify several novel players and key early steps responsible for initiation, restriction, and propagation of left-right asymmetry during embryogenesis of a non-chordate deuterostome and uncover a functional link between the H+/K+-ATPase and the Notch signaling pathway. PMID:23271979

A Field and Simulator Evaluation of All-Red Clearance Intervals for Use in Left-Turn Applications

DOT National Transportation Integrated Search

2018-03-01

As the implementation of the novel flashing yellow arrow (FYA) traffic control device advances throughout the country, agencies continually seek ways to improve intersection operations and safety, especially on left turns. For example, permissive lef...

To signal or not to signal: that should not be the question.

PubMed

Faw, Harold W

2013-10-01

The purpose of the present research was to examine rates of turn signal use, a positive and potentially valuable means by which drivers can communicate. A second purpose was to explore factors that might impact these rates, including the modeling influence of other drivers. A series of observations involving more than 5600 vehicles making turns were recorded at a variety of intersections in British Columbia, Canada. Though the occurrence of signal use varied widely, ranging from a low of 54% to a high of 95%, the overall rate was 76%. Drivers used turn signals significantly less often when making right as compared with left turns, when traffic volume was higher, and when a designated turning lane was provided. In addition, compared with drivers following another vehicle not using signals, those following a vehicle with turn signals on were significantly more likely to activate their turn signals, suggesting a possible modeling effect. Both internal and external influences on turn signal use by drivers were considered. External factors explored in this research included direction of turn, traffic volume, intersection configuration, and the example of other drivers. It was concluded that the practice of signaling turns merits more research attention, since consistent use of signals is a potential contributor to enhanced safety for all road users. Copyright © 2013 Elsevier Ltd. All rights reserved.

Development of guidelines for pedestrian safety treatments at signalized intersections.

DOT National Transportation Integrated Search

2012-01-01

For intersections with a permissive or protected-permissive left-turn mode, pedestrians cross during the : permissive period. This operation requires the left-turn driver to yield to both opposing vehicles and : pedestrians, prior to accepting a gap ...

Overload protection circuit for output driver

DOEpatents

Stewart, Roger G.

1982-05-11

A protection circuit for preventing excessive power dissipation in an output transistor whose conduction path is connected between a power terminal and an output terminal. The protection circuit includes means for sensing the application of a turn on signal to the output transistor and the voltage at the output terminal. When the turn on signal is maintained for a period of time greater than a given period without the voltage at the output terminal reaching a predetermined value, the protection circuit decreases the turn on signal to, and the current conduction through, the output transistor.

Effects of major-road vehicle speed and driver age and gender on left-turn gap acceptance.

PubMed

Yan, Xuedong; Radwan, Essam; Guo, Dahai

2007-07-01

Because the driver's gap-acceptance maneuver is a complex and risky driving behavior, it is a highly concerned topic for traffic safety and operation. Previous studies have mainly focused on the driver's gap acceptance decision itself but did not pay attention to the maneuver process and driving behaviors. Using a driving simulator experiment for left-turn gap acceptance at a stop-controlled intersection, this study evaluated the effects of major traffic speed and driver age and gender on gap acceptance behaviors. The experiment results illustrate relationships among drivers' left-turn gap decision, driver's acceleration rate, steering action, and the influence of the gap-acceptance maneuver on the vehicles in the major traffic stream. The experiment results identified an association between high crash risk and high traffic speed at stop-controlled intersections. The older drivers, especially older female drivers, displayed a conservative driving attitude as a compensation for reduced driving ability, but also showed to be the most vulnerable group for the relatively complex driving maneuvers.

Right-­turn traffic volume adjustment in traffic signal warrant analysis : final report.

DOT National Transportation Integrated Search

2016-05-06

This report was based on the research project, Right-Turn Traffic Volume Adjustment in Traffic Signal Warrants, sponsored by the Nevada Department of Transportation (NDOT) and SOLARIS. Right-turn traffic does not affect intersection performance in th...

Left-handed helical preference in an achiral peptide chain is induced by an L-amino acid in an N-terminal type II β-turn.

PubMed

De Poli, Matteo; De Zotti, Marta; Raftery, James; Aguilar, Juan A; Morris, Gareth A; Clayden, Jonathan

2013-03-15

Oligomers of the achiral amino acid Aib adopt helical conformations in which the screw-sense may be controlled by a single N-terminal residue. Using crystallographic and NMR techniques, we show that the left- or right-handed sense of helical induction arises from the nature of the β-turn at the N terminus: the tertiary amino acid L-Val induces a left-handed type II β-turn in both the solid state and in solution, while the corresponding quaternary amino acid L-α-methylvaline induces a right-handed type III β-turn.

The impact of general permissive right and left turn on red legislation in Virginia.

DOT National Transportation Integrated Search

1978-01-01

Right turn on red (RTOR) maneuvers have been permitted at signalized intersections in Virginia since 1972. However, until January 1, 1977, following a study requested by the General Assembly, the maneuver was restricted to intersections at which a si...

Intelligent Automatic Right-Left Sign Lamp Based on Brain Signal Recognition System

NASA Astrophysics Data System (ADS)

Winda, A.; Sofyan; Sthevany; Vincent, R. S.

2017-12-01

Comfort as a part of the human factor, plays important roles in nowadays advanced automotive technology. Many of the current technologies go in the direction of automotive driver assistance features. However, many of the driver assistance features still require physical movement by human to enable the features. In this work, the proposed method is used in order to make certain feature to be functioning without any physical movement, instead human just need to think about it in their mind. In this work, brain signal is recorded and processed in order to be used as input to the recognition system. Right-Left sign lamp based on the brain signal recognition system can potentially replace the button or switch of the specific device in order to make the lamp work. The system then will decide whether the signal is ‘Right’ or ‘Left’. The decision of the Right-Left side of brain signal recognition will be sent to a processing board in order to activate the automotive relay, which will be used to activate the sign lamp. Furthermore, the intelligent system approach is used to develop authorized model based on the brain signal. Particularly Support Vector Machines (SVMs)-based classification system is used in the proposed system to recognize the Left-Right of the brain signal. Experimental results confirm the effectiveness of the proposed intelligent Automatic brain signal-based Right-Left sign lamp access control system. The signal is processed by Linear Prediction Coefficient (LPC) and Support Vector Machines (SVMs), and the resulting experiment shows the training and testing accuracy of 100% and 80%, respectively.

Timing performance of a self-cancelling turn-signal mechanism in motorcycles based on the ATMega328P microcontroller

NASA Astrophysics Data System (ADS)

Nurbuwat, Adzin Kondo; Eryandi, Kholid Yusuf; Estriyanto, Yuyun; Widiastuti, Indah; Pambudi, Nugroho Agung

2018-02-01

The objective of this study is to measure the time performance of a self-cancelling turn signal mechanism based on the In this study the performance of self-cancelling turn signal based on ATMega328P microcontroller is measured at low speed and high speed treatment on motorcycles commonly used in Indonesia. Time performance measurements were made by comparing the self-cancelling turn signal based on ATMega328P microcontroller with standard motor turn time. Measurements of time at low speed treatment were performed at a speed range of 15 km / h, 20 km / h, 25 km / h on the U-turn test trajectory. The angle of the turning angle of the potentiometer is determined at 3°. The limit of steering wheel turning angle at the potentiometer is set at 3°. For high-speed treatment is 30 km / h, 40 km / h, 50km / h, and 60 km / h, on the L-turn test track with a tilt angle (roll angle) read by the L3G4200D gyroscope sensor. Each speed test is repeated 3 replications. Standard time is a reference for self-cancelling turn signal performance. The standard time obtained is 15.68 s, 11.96 s, 9.34 s at low speed and 4.63 s, 4.06 s, 3.61 s, 3.13 s at high speed. The time test of self-cancelling turn signal shows 16.10 s, 12.42 s, 10.24 s at the low speed and 5.18, 4.51, 3.73, 3.21 at the high speed. At a speed of 15 km / h occurs the instability of motion turns motorcycle so that testing is more difficult. Small time deviations indicate the tool works well. The largest time deviation value is 0.9 seconds at low speed and 0.55 seconds at high speed. The conclusion at low velocity of the highest deviation value occurred at the speed of 25 km / h test due to the movement of slope with inclination has started to happen which resulted in slow reading of steering movement. At higher speeds the time slows down due to rapid sensor readings on the tilt when turning fast at ever higher speeds. The timing performance of self-cancelling turn signal decreases as the motorcycle turning

Improved Safety and Efficiency of Protected/Permitted Right-Turns in Oregon

DOT National Transportation Integrated Search

2018-05-01

This research aimed to develop an understanding of the safety and operational implications of using the flashing yellow arrow (FYA) in permitted and protected/permitted right turn (PPRT) operations to maximize safety and efficiency. This report inclu...

Bolivia’s Left Turn Toward Rentier Plurinationalism And Its Effects On Ethnic Tensions And Solidarity

DTIC Science & Technology

2016-06-01

utilities and gas pipelines sparked a broad societal solidarity movement against transnational corporate control of water and gas . The 2000 Water Wars...Constitution referendum, funds for social programs were to be allocated exclusively from hydrocarbon and natural gas rents. A. BOLIVIA’S LEFT TURN...Cartographies,” 991–992. 4 sector toward nationalization. The Bolivian energy sector, “natural gas , in particular” has “become the backbone of the

Contribution of Hedgehog signaling to the establishment of left-right asymmetry in the sea urchin

PubMed Central

Warner, Jacob F.; Miranda, Esther L.; McClay, David R.

2016-01-01

Summary Most bilaterians exhibit a left-right asymmetric distribution of their internal organs. The sea urchin larva is notable in this regard since most adult structures are generated from left sided embryonic structures. The gene regulatory network governing this larval asymmetry is still a work in progress but involves several conserved signaling pathways including Nodal, and BMP. Here we provide a comprehensive analysis of Hedgehog signaling and it’s contribution to left-right asymmetry. We report that Hh signaling plays a conserved role to regulate late asymmetric expression of Nodal and that this regulation occurs after Nodal breaks left-right symmetry in the mesoderm. Thus, while Hh functions to maintain late Nodal expression, the molecular asymmetry of the future coelomic pouches is locked in. Furthermore we report that cilia play a role only insofar as to transduce Hh signaling and do not have an independent effect on the asymmetry of the mesoderm. From this, we are able to construct a more complete regulatory network governing the establishment of left-right asymmetry in the sea urchin. PMID:26872875

Contribution of hedgehog signaling to the establishment of left-right asymmetry in the sea urchin.

PubMed

Warner, Jacob F; Miranda, Esther L; McClay, David R

2016-03-15

Most bilaterians exhibit a left-right asymmetric distribution of their internal organs. The sea urchin larva is notable in this regard since most adult structures are generated from left sided embryonic structures. The gene regulatory network governing this larval asymmetry is still a work in progress but involves several conserved signaling pathways including Nodal, and BMP. Here we provide a comprehensive analysis of Hedgehog signaling and it's contribution to left-right asymmetry. We report that Hh signaling plays a conserved role to regulate late asymmetric expression of Nodal and that this regulation occurs after Nodal breaks left-right symmetry in the mesoderm. Thus, while Hh functions to maintain late Nodal expression, the molecular asymmetry of the future coelomic pouches is locked in. Furthermore we report that cilia play a role only insofar as to transduce Hh signaling and do not have an independent effect on the asymmetry of the mesoderm. From this, we are able to construct a more complete regulatory network governing the establishment of left-right asymmetry in the sea urchin. Copyright © 2016 Elsevier Inc. All rights reserved.

32 CFR 636.23 - Turning movements.

Code of Federal Regulations, 2014 CFR

2014-07-01

... from a position as close to the right edge or right curb of the roadway as possible. (c) Left-turns will be made from a position as close to the center line as possible or from a left turn lane, if...

32 CFR 636.23 - Turning movements.

Code of Federal Regulations, 2012 CFR

2012-07-01

... from a position as close to the right edge or right curb of the roadway as possible. (c) Left-turns will be made from a position as close to the center line as possible or from a left turn lane, if...

Rapamycin Protects against Myocardial Ischemia-Reperfusion Injury through JAK2-STAT3 Signaling Pathway

PubMed Central

Das, Anindita; Salloum, Fadi N.; Durrant, David; Ockaili, Ramzi; Kukreja, Rakesh C

2012-01-01

Rapamycin (Sirolimus®) is used to prevent rejection of transplanted organs and coronary restenosis. We reported that rapamycin induced cardioprotection against ischemia-reperfusion (I/R) injury through opening of mitochondrial KATP channels. However, signaling mechanisms in rapamycin-induced cardioprotection are currently unknown. Considering that STAT3 is protective in the heart, we investigated the potential role of this transcription factor in rapamycin-induced protection against (I/R) injury. Adult male ICR mice were treated with rapamycin (0.25 mg/kg, i.p.) or vehicle (DMSO) with/without inhibitor of JAK2 (AG-490) or STAT3 (stattic). One hour later, the hearts were subjected to I/R either in Langendorf mode or in situ ligation of left coronary artery. Additionally, primary murine cardiomyocytes were subjected to simulated ischemia/reoxygenation (SI-RO) injury in vitro. For in situ targeted knockdown of STAT3, lentiviral vector containing short hairpin RNA was injected into left ventricle 3 weeks prior to initiating I/R injury. Infarct size, cardiac function, cardiomyocyte necrosis and apoptosis were assessed. Rapamycin reduced infarct size, improved cardiac function following I/R, limited cardiomyocytes necrosis as well as apoptosis following SI-RO which were blocked by AG-490 and stattic. In situ knock-down of STAT3 attenuated rapamycin-induced protection against I/R injury. Rapamycin triggered unique cardioprotecive signaling including phosphorylation of ERK, STAT3, eNOS and glycogen synthase kinase-3β in concert with increased prosurvival Bcl-2 to Bax ratio. Our data suggest that JAK2-STAT3 signaling plays an essential role in rapamycin-induced cardioprotection. We propose that rapamycin is a novel and clinically relevant pharmacological strategy to target STAT3 activation for treatment of myocardial infarction. PMID:22999860

The use of intonation for turn anticipation in observed conversations without visual signals as source of information

PubMed Central

Keitel, Anne; Daum, Moritz M.

2015-01-01

The anticipation of a speaker’s next turn is a key element of successful conversation. This can be achieved using a multitude of cues. In natural conversation, the most important cue for adults to anticipate the end of a turn (and therefore the beginning of the next turn) is the semantic and syntactic content. In addition, prosodic cues, such as intonation, or visual signals that occur before a speaker starts speaking (e.g., opening the mouth) help to identify the beginning and the end of a speaker’s turn. Early in life, prosodic cues seem to be more important than in adulthood. For example, it was previously shown that 3-year-old children anticipated more turns in observed conversations when intonation was available compared with when not, and this beneficial effect was present neither in younger children nor in adults (Keitel et al., 2013). In the present study, we investigated this effect in greater detail. Videos of conversations between puppets with either normal or flattened intonation were presented to children (1-year-olds and 3-year-olds) and adults. The use of puppets allowed the control of visual signals: the verbal signals (speech) started exactly at the same time as the visual signals (mouth opening). With respect to the children, our findings replicate the results of the previous study: 3-year-olds anticipated more turns with normal intonation than with flattened intonation, whereas 1-year-olds did not show this effect. In contrast to our previous findings, the adults showed the same intonation effect as the 3-year-olds. This suggests that adults’ cue use varies depending on the characteristics of a conversation. Our results further support the notion that the cues used to anticipate conversational turns differ in development. PMID:25713548

Is lipid signaling through cannabinoid 2 receptors part of a protective system?

PubMed Central

Pacher, P.; Mechoulam, R.

2011-01-01

The mammalian body has a highly developed immune system which guards against continuous invading protein attacks and aims at preventing, attenuating or repairing the inflicted damage. It is conceivable that through evolution analogous biological protective systems have been evolved against non-protein attacks. There is emerging evidence that lipid endocannabinoid signaling through cannabinoid 2 (CB2) receptors may represent an example/part of such a protective system/armamentarium. Inflammation/tissue injury triggers rapid elevations in local endocannabinoid levels, which in turn regulate signaling responses in immune and other cells modulating their critical functions. Changes in endocannabinoid levels and/or CB2 receptor expressions have been reported in almost all diseases affecting humans, ranging from cardiovascular, gastrointestinal, liver, kidney, neurodegenerative, psychiatric, bone, skin, auto-immune, lung disorders to pain and cancer, and modulating CB2 receptor activity holds tremendous therapeutic potential in these pathologies. While CB2 receptor activation in general mediates immunosuppressive effects, which limit inflammation and associated tissue injury in large number of pathological conditions, in some disease states activation of the CB2 receptor may enhance or even trigger tissue damage, which will also be discussed alongside the protective actions of the CB2 receptor stimulation with endocannabinoids or synthetic agonists, and the possible biological mechanisms involved in these effects. PMID:21295074

Is lipid signaling through cannabinoid 2 receptors part of a protective system?

PubMed

Pacher, P; Mechoulam, R

2011-04-01

The mammalian body has a highly developed immune system which guards against continuous invading protein attacks and aims at preventing, attenuating or repairing the inflicted damage. It is conceivable that through evolution analogous biological protective systems have been evolved against non-protein attacks. There is emerging evidence that lipid endocannabinoid signaling through cannabinoid 2 (CB₂) receptors may represent an example/part of such a protective system/armamentarium. Inflammation/tissue injury triggers rapid elevations in local endocannabinoid levels, which in turn regulate signaling responses in immune and other cells modulating their critical functions. Changes in endocannabinoid levels and/or CB₂ receptor expressions have been reported in almost all diseases affecting humans, ranging from cardiovascular, gastrointestinal, liver, kidney, neurodegenerative, psychiatric, bone, skin, autoimmune, lung disorders to pain and cancer, and modulating CB₂ receptor activity holds tremendous therapeutic potential in these pathologies. While CB₂ receptor activation in general mediates immunosuppressive effects, which limit inflammation and associated tissue injury in large number of pathological conditions, in some disease states activation of the CB₂ receptor may enhance or even trigger tissue damage, which will also be discussed alongside the protective actions of the CB₂ receptor stimulation with endocannabinoids or synthetic agonists, and the possible biological mechanisms involved in these effects. Published by Elsevier Ltd.

Evaluating the Operational Features of an Unconventional Dual-Bay U-Turn Design for Intersections.

PubMed

Xiang, Yun; Li, Zhibin; Wang, Wei; Chen, Jingxu; Wang, Hao; Li, Ye

2016-01-01

Median U-turn intersection treatment (MUTIT) has been considered an alternative measure to reduce congestion and traffic conflict at intersection areas. The MUTIT is sometimes difficult to implement in the field because it requires wide median on arterials for U-turn vehicles. The objective of this study is to introduce an unconventional U-turn treatment (UUT) for intersections which requires less median space but is also effective. The UUT has a dual-bay design with different turning radiuses for small and large vehicles. The VISSIM simulation model was developed to evaluate the operational features of the UUT. The model was calibrated using data collected from intersections in China. The capacity, delay and number of stops were evaluated and compared with the direct-left-turn (DLT) for the same intersections. The results showed that the UUT significantly improved the operations at intersection areas, especially when volume/capacity ratio is small, and ratio of left-turn to through traffic is small. With the UUT, the capacity is increased by 9.81% to 10.38%, vehicle delay is decreased by 18.5% to 40.1%, and number of stops is decreased by 23.19% to 36.62%, when volume/capacity ratio is less than 0.50. The study also found that traffic efficiency could be further improved when the UUT is designed in conjunction with signal control. In the case, the UUT plus signalized control increases the capacity by 25% to 26.02%, decreases vehicle delay by 50.5% to 55.8%, and reduces number of stops by 69.5%, compared with the traditional DLT.

Tune Evaluation From Phased BPM Turn-By-Turn Data

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

Alexahin, Y.; Gianfelice-Wendt, E.; Marsh, W.

2010-05-18

In fast ramping synchrotrons like the Fermilab Booster the conventional methods of betatron tune evaluation from the turn-by-turn data may not work due to rapid changes of the tunes (sometimes in a course of a few dozens of turns) and a high level of noise. We propose a technique based on phasing of signals from a large number of BPMs which significantly increases the signal to noise ratio. Implementation of the method in the Fermilab Booster control system is described and some measurement results are presented.

Left-turn lanes at unsignalized median openings.

DOT National Transportation Integrated Search

2014-03-01

Due to the frequent presence of median openings in urban arterial settings, the requirements for the deceleration and : storage of turning vehicles (e.g. AASHTO Green Book) often exceed the available length between two adjacent : openings which leave...

49 CFR 236.14 - Spring switch signal protection; requirements.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 4 2012-10-01 2012-10-01 false Spring switch signal protection; requirements. 236... Rules and Instructions: All Systems General § 236.14 Spring switch signal protection; requirements. (a... track signaled for movements in only one direction through a spring switch in automatic block signal...

49 CFR 236.14 - Spring switch signal protection; requirements.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false Spring switch signal protection; requirements. 236... Rules and Instructions: All Systems General § 236.14 Spring switch signal protection; requirements. (a... track signaled for movements in only one direction through a spring switch in automatic block signal...

49 CFR 236.14 - Spring switch signal protection; requirements.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 4 2011-10-01 2011-10-01 false Spring switch signal protection; requirements. 236... Rules and Instructions: All Systems General § 236.14 Spring switch signal protection; requirements. (a... track signaled for movements in only one direction through a spring switch in automatic block signal...

49 CFR 236.14 - Spring switch signal protection; requirements.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 4 2013-10-01 2013-10-01 false Spring switch signal protection; requirements. 236... Rules and Instructions: All Systems General § 236.14 Spring switch signal protection; requirements. (a... track signaled for movements in only one direction through a spring switch in automatic block signal...

49 CFR 236.14 - Spring switch signal protection; requirements.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 4 2014-10-01 2014-10-01 false Spring switch signal protection; requirements. 236... Rules and Instructions: All Systems General § 236.14 Spring switch signal protection; requirements. (a... track signaled for movements in only one direction through a spring switch in automatic block signal...

Evaluating the Operational Features of an Unconventional Dual-Bay U-Turn Design for Intersections

PubMed Central

Xiang, Yun; Li, Zhibin; Wang, Wei; Chen, Jingxu; Wang, Hao; Li, Ye

2016-01-01

Median U-turn intersection treatment (MUTIT) has been considered an alternative measure to reduce congestion and traffic conflict at intersection areas. The MUTIT is sometimes difficult to implement in the field because it requires wide median on arterials for U-turn vehicles. The objective of this study is to introduce an unconventional U-turn treatment (UUT) for intersections which requires less median space but is also effective. The UUT has a dual-bay design with different turning radiuses for small and large vehicles. The VISSIM simulation model was developed to evaluate the operational features of the UUT. The model was calibrated using data collected from intersections in China. The capacity, delay and number of stops were evaluated and compared with the direct-left-turn (DLT) for the same intersections. The results showed that the UUT significantly improved the operations at intersection areas, especially when volume/capacity ratio is small, and ratio of left-turn to through traffic is small. With the UUT, the capacity is increased by 9.81% to 10.38%, vehicle delay is decreased by 18.5% to 40.1%, and number of stops is decreased by 23.19% to 36.62%, when volume/capacity ratio is less than 0.50. The study also found that traffic efficiency could be further improved when the UUT is designed in conjunction with signal control. In the case, the UUT plus signalized control increases the capacity by 25% to 26.02%, decreases vehicle delay by 50.5% to 55.8%, and reduces number of stops by 69.5%, compared with the traditional DLT. PMID:27467127

Evaluating the Effects of Traffic on Driver Stopping and Turn Signal Use at a Stop Sign: A Systematic Replication

ERIC Educational Resources Information Center

Lebbon, Angela R.; Austin, John; Van Houten, Ron; Malenfant, Louis E.

2007-01-01

The current analyses of observational data found that oncoming traffic substantially affected driver stopping patterns and turn signal use at the target stop sign. The percentage of legal stops and turn signal use by drivers in the presence and absence of traffic was analyzed using a multi-element design. The results showed that legal stops were…

Dynamic flashing yellow arrow (FYA): a study on variable left-turn mode operational and safety impacts phase II - model expansion and testing : [summary].

DOT National Transportation Integrated Search

2016-05-01

In phase two of this project, the UCF team further developed the DSS to automate selection of FYA left-turn modes based on traffic volumes at intersections acquired in real time from existing sensors.

49 CFR 236.12 - Spring switch signal protection; where required.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 4 2014-10-01 2014-10-01 false Spring switch signal protection; where required... Rules and Instructions: All Systems General § 236.12 Spring switch signal protection; where required. Signal protection shall be provided for facing and trailing movements through spring switch within...

49 CFR 236.12 - Spring switch signal protection; where required.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 4 2011-10-01 2011-10-01 false Spring switch signal protection; where required... Rules and Instructions: All Systems General § 236.12 Spring switch signal protection; where required. Signal protection shall be provided for facing and trailing movements through spring switch within...

49 CFR 236.12 - Spring switch signal protection; where required.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 4 2012-10-01 2012-10-01 false Spring switch signal protection; where required... Rules and Instructions: All Systems General § 236.12 Spring switch signal protection; where required. Signal protection shall be provided for facing and trailing movements through spring switch within...

49 CFR 236.12 - Spring switch signal protection; where required.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 4 2013-10-01 2013-10-01 false Spring switch signal protection; where required... Rules and Instructions: All Systems General § 236.12 Spring switch signal protection; where required. Signal protection shall be provided for facing and trailing movements through spring switch within...

49 CFR 236.12 - Spring switch signal protection; where required.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false Spring switch signal protection; where required... Rules and Instructions: All Systems General § 236.12 Spring switch signal protection; where required. Signal protection shall be provided for facing and trailing movements through spring switch within...

Traditional Chinese medicine suppresses left ventricular hypertrophy by targeting extracellular signal-regulated kinases signaling pathway in spontaneously hypertensive rats

PubMed Central

Xiong, Xingjiang; Yang, Xiaochen; Duan, Lian; Liu, Wei; Zhang, Yun; Liu, Yongmei; Wang, Pengqian; Li, Shengjie; Li, Xiaoke

2017-01-01

Chinese herbal medicine Bu-Shen-Jiang-Ya decoction (BSJYD) is reported to be beneficial for hypertension. Over expression of extracellular signal regulated kinases (ERK) pathway plays an important role in left ventricular hypertrophy (LVH). This study aimed to observe effects of BSJYD on LVH in spontaneously hypertensive rats (SHRs) and explore its possible mechanism on regulation of ERK pathway. Sixty 12-week-old SHRs were randomly allocated into 5 groups: BSJYD high dose group, middle dose group, low dose group, captopril group, and control group. Besides, a control group of Wistar-Kyoto rats was established. All rats were treated for 8 weeks. Systolic blood pressure (SBP), heart rate (HR), pathology, and left ventricular mass index (LVMI) were measured. Western blotting and Real-time PCR were used to assess the expressions of BDNF, Ras, ERK1/2, and c-fox levels. SBP and HR were significantly decreased compared with the control group and LVMI was markedly improved by BSJYD treatment in a dose-dependent manner. BSJYD inhibited the expression of BDNF, Ras, ERK1/2, and c-fox mRNA in LVH. In conclusion, BSJYD suppressed hypertension-induced cardiac hypertrophy by inhibiting the expression of ERK pathway. These changes in gene expression may be a possible mechanism by which BSJYD provides myocardial protection from hypertension. PMID:28225023

[Backward flow signal in the left atrium studied by Doppler echocardiography. Differentiation from mitral regurgitation].

PubMed

Nagoshi, H; Miyairi, M; Asato, T; Naito, M; Honda, M

1983-03-01

A backward flow signal in the left atrium masquerading as mitral regurgitation was studied by a pulsed Doppler method. The subjects consisted of 20 normal volunteers, 12 cases with mitral valve prolapse syndrome, five cases with rheumatic mitral regurgitation, five cases with lone atrial fibrillation, four cases with asymmetric septal hypertrophy and three cases with the Björk-Shiley tilting disc valve in the mitral position. In two-dimensional echocardiography combined with pulsed Doppler method, a Doppler signal was recorded by locating a sample volume in the left atrium. In all of the cases with mitral valve prolapse syndrome and the cases with the prosthetic valve as well as in all of the normal subjects, the backward flow signal was observed in the left atrium. In three cases with mitral valve prolapse syndrome, it was differentiated from a transvalvular regurgitant flow signal. In all cases with rheumatic mitral regurgitation, the backward flow signal was masked by a turbulent flow signal representing regurgitation. In cases with mitral stenosis, the backward flow signal was scarcely recognized. The duration of the backward flow signal had no relationship with heart rate. The histogram of incidence on the scale of R-R interval revealed normal distribution with a mean value of 0.24 sec (+/- 0.09 sec). Therefore, in cases with tachycardia, the backward flow signal was seen throughout systole. The peak backward flow velocity of Doppler signals was correlated (r = 0.71, p less than 0.01) with the peak forward flow velocity in diastole. The faint backward flow signal seen in cases with mitral stenosis and post-extrasystolic potentiation of the backward flow signal were suggestive of the foregoing relationship. The mechanism producing the backward flow was postulated as a water hammer phenomenon caused by closure of the mitral valve.

Asymmetry of flight and escape turning responses in horses.

PubMed

Austin, N P; Rogers, L J

2007-09-01

We investigated whether horses display greater reactivity to a novel stimulus presented in the left compared to the right monocular visual field, and whether a population bias exists for escape turning when the same stimulus was presented binocularly. Domestic horses (N=30) were tested on three occasions by a person opening an umbrella five metres away and then approaching. The distance each horse moved away before stopping was measured. Distance was greatest for approach on the left side, indicating right hemisphere control of flight behaviour, and thus followed the same pattern found previously in other species. When order of monocular presentation was considered, an asymmetry was detected. Horses tested initially on the left side exhibited greater reactivity for left approach, whereas horses tested on the right side first displayed no side difference in reactivity. Perhaps left hemisphere inhibition of flight response allowed horses to learn that the stimulus posed no threat and this information was transferred to the right hemisphere. No population bias existed for the direction of escape turning, but horses that turned to the right when approached from the front were found to exhibit longer flight distances than those that turned to the left.

Design criteria for median turn lanes.

DOT National Transportation Integrated Search

1978-03-01

This study was initiated with an extensive literature review and survey of : left-turn median lane practices in Texas cities. The initial phase identified : characteristics of urban arterial accidents, basic design elements, current use of : left-tur...

Analysis of EEG signal by flicker-noise spectroscopy: identification of right-/left-hand movement imagination.

PubMed

Broniec, A

2016-12-01

Flicker-noise spectroscopy (FNS) is a general phenomenological approach to analyzing dynamics of complex nonlinear systems by extracting information contained in chaotic signals. The main idea of FNS is to describe an information hidden in correlation links, which are present in the chaotic component of the signal, by a set of parameters. In the paper, FNS is used for the analysis of electroencephalography signal related to the hand movement imagination. The signal has been parametrized in accordance with the FNS method, and significant changes in the FNS parameters have been observed, at the time when the subject imagines the movement. For the right-hand movement imagination, abrupt changes (visible as a peak) of the parameters, calculated for the data recorded from the left hemisphere, appear at the time corresponding to the initial moment of the imagination. In contrary, for the left-hand movement imagination, the meaningful changes in the parameters are observed for the data recorded from the right hemisphere. As the motor cortex is activated mainly contralaterally to the hand, the analysis of the FNS parameters allows to distinguish between the imagination of the right- and left-hand movement. This opens its potential application in the brain-computer interface.

Safety of percutaneous left atrial appendage closure: results from the Watchman Left Atrial Appendage System for Embolic Protection in Patients with AF (PROTECT AF) clinical trial and the Continued Access Registry.

PubMed

Reddy, Vivek Y; Holmes, David; Doshi, Shephal K; Neuzil, Petr; Kar, Saibal

2011-02-01

The Watchman Left Atrial Appendage System for Embolic Protection in Patients With AF (PROTECT AF) randomized trial compared left atrial appendage closure against warfarin in atrial fibrillation (AF) patients with CHADS₂ ≥1. Although the study met the primary efficacy end point of being noninferior to warfarin therapy for the prevention of stroke/systemic embolism/cardiovascular death, there was a significantly higher risk of complications, predominantly pericardial effusion and procedural stroke related to air embolism. Here, we report the influence of experience on the safety of percutaneous left atrial appendage closure. The study cohort for this analysis included patients in the PROTECT AF trial who underwent attempted device left atrial appendage closure (n=542 patients) and those from a subsequent nonrandomized registry of patients undergoing Watchman implantation (Continued Access Protocol [CAP] Registry; n=460 patients). The safety end point included bleeding- and procedure-related events (pericardial effusion, stroke, device embolization). There was a significant decline in the rate of procedure- or device-related safety events within 7 days of the procedure across the 2 studies, with 7.7% and 3.7% of patients, respectively, experiencing events (P=0.007), and between the first and second halves of PROTECT AF and CAP, with 10.0%, 5.5%, and 3.7% of patients, respectively, experiencing events (P=0.006). The rate of serious pericardial effusion within 7 days of implantation, which had made up >50% of the safety events in PROTECT AF, was lower in the CAP Registry (5.0% versus 2.2%, respectively; P=0.019). There was a similar experience-related improvement in procedure-related stroke (0.9% versus 0%, respectively; P=0.039). Finally, the functional impact of these safety events, as defined by significant disability or death, was statistically superior in the Watchman group compared with the warfarin group in PROTECT AF. This remained true whether significance

Capacity Estimation Model for Signalized Intersections under the Impact of Access Point

PubMed Central

Zhao, Jing; Li, Peng; Zhou, Xizhao

2016-01-01

Highway Capacity Manual 2010 provides various factors to adjust the base saturation flow rate for the capacity analysis of signalized intersections. No factors, however, is considered for the potential change of signalized intersections capacity caused by the access point closeing to the signalized intersection. This paper presented a theoretical model to estimate the lane group capacity at signalized intersections with the consideration of the effects of access points. Two scenarios of access point locations, upstream or downstream of the signalized intersection, and impacts of six types of access traffic flow are taken into account. The proposed capacity model was validated based on VISSIM simulation. Results of extensive numerical analysis reveal the substantial impact of access point on the capacity, which has an inverse correlation with both the number of major street lanes and the distance between the intersection and access point. Moreover, among the six types of access traffic flows, the access traffic flow 1 (right-turning traffic from major street), flow 4 (left-turning traffic from access point), and flow 5 (left-turning traffic from major street) cause a more significant effect on lane group capacity than others. Some guidance on the mitigation of the negative effect is provided for practitioners. PMID:26726998

Effect of Pedestrians on the Saturation Flow Rate of Right Turn Movements at Signalized Intersection - Case Study from Rasht City

NASA Astrophysics Data System (ADS)

Roshani, Mostafa; Bargegol, Iraj

2017-10-01

Saturation flow rate is one of the important items in the analysis of the capacity of signalized intersections that are affected by some factors. Pedestrian crossing on signalized intersection is one of the factors which influence the vehicles flow. In addition, the released researches determined that the greatest impact of pedestrian on the saturation flow occurred in the Conflict zone where the highest chance of the encounter of pedestrians and vehicles has in turning movements. The purpose of this paper is to estimate the saturation flow rate considering the effect of a pedestrian on right turn movements of the signalized intersections in Rasht city. For this goal, 6 signalized intersections with 90 cycles of reviews were selected for the estimation of saturation flow rate by the microscopic method and also 3 right turn lanes containing radius differences with 70 cycles of reviews were collected for the investigation of the pedestrians’ effects. Each phase of right turn lanes cycle was divided in the pieces of 10-second period which was totally 476 sample volumes of considered pedestrians and vehicles at that period. Only 101 samples of those were ranged as saturated conditions. Finally, using different regression models, the best relationship between pedestrian’s volume and right turning vehicles flow parameters was evaluated. The results indicate that there is a primarily linear relationship between pedestrian volume and right turning vehicles flow with R2=0.6261. According to this regression model with the increase in pedestrians, saturation flow rate will be reduced. In addition, by comparing the adjustment factor obtained in the present study and other studies, it was found that the effect of pedestrians on the right-turn movements in Rasht city is less than the rest of the world.

Rationale of cerebral protection devices in left atrial appendage occlusion.

PubMed

Meincke, Felix; Spangenberg, Tobias; Kreidel, Felix; Frerker, Christian; Virmani, Renu; Ladich, Elena; Kuck, Karl-Heinz; Ghanem, Alexander

2017-01-01

Aims of this case-series were to assess the feasibility of cerebral protection devices in interventional left atrial appendage occlusion (iLAAO) procedures and to yield insight into the pathomorphological correlate of early, procedural cerebral embolization during iLAAO. Five consecutive patients underwent iLLO flanked by the Sentinel CPS® (Claret Medical, Inc., Santa Rosa, CA) cerebral protection system. Placement and recapture of the Sentinel ® device as well as the iLAAO were successful and safe in all cases. Histomorphometric analysis of the collected filters showed embolized debris in all patients. Acute thrombus was found in three patients, organizing thrombus in four. Interestingly, two patients had endocardial or myocardial tissue in their filters. Cerebral protection during iLAAO with the Sentinel CPS ® device is feasible. Furthermore, this dataset identifies the formation and embolization of thrombus and cardiac tissue as emboligeneic sources and potential future targets to reduce procedural complications. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Applying Bayesian hierarchical models to examine motorcycle crashes at signalized intersections.

PubMed

Haque, Md Mazharul; Chin, Hoong Chor; Huang, Helai

2010-01-01

Motorcycles are overrepresented in road traffic crashes and particularly vulnerable at signalized intersections. The objective of this study is to identify causal factors affecting the motorcycle crashes at both four-legged and T signalized intersections. Treating the data in time-series cross-section panels, this study explores different Hierarchical Poisson models and found that the model allowing autoregressive lag-1 dependence specification in the error term is the most suitable. Results show that the number of lanes at the four-legged signalized intersections significantly increases motorcycle crashes largely because of the higher exposure resulting from higher motorcycle accumulation at the stop line. Furthermore, the presence of a wide median and an uncontrolled left-turn lane at major roadways of four-legged intersections exacerbate this potential hazard. For T signalized intersections, the presence of exclusive right-turn lane at both major and minor roadways and an uncontrolled left-turn lane at major roadways increases motorcycle crashes. Motorcycle crashes increase on high-speed roadways because they are more vulnerable and less likely to react in time during conflicts. The presence of red light cameras reduces motorcycle crashes significantly for both four-legged and T intersections. With the red light camera, motorcycles are less exposed to conflicts because it is observed that they are more disciplined in queuing at the stop line and less likely to jump start at the start of green.

Family matters: Directionality of turning bias while kissing is modulated by context.

PubMed

Sedgewick, Jennifer R; Elias, Lorin J

2016-01-28

When leaning forward to kiss to a romantic partner, individuals tend to direct their kiss to the right more often than the left. Studies have consistently demonstrated this kissing asymmetry, although other factors known to influence lateral biases, such as sex or situational context, had yet to be explored. The primary purpose of our study was to investigate if turning direction was consistent between a romantic (parent-parent) and parental (parent-child) kissing context, and secondly, to examine if sex differences influenced turning bias between parent-child kissing partners. An archival analysis coded the direction of turning bias for 161 images of romantic kissing (mothers kissing fathers) and 529 images of parental kissing (mothers or fathers kissing sons or daughters). The results indicated that the direction of turning bias differed between kissing contexts. As expected, a right-turn bias was observed for romantic kissing; however, a left-turn bias was exhibited for parental kissing. There was no significant difference of turning bias between any parent-child kissing partners. Interpretations for the left-turn bias discuss parental kissing as a learned lateral behaviour.

Targeted deletion of apoptosis signal-regulating kinase 1 attenuates left ventricular remodeling

PubMed Central

Yamaguchi, Osamu; Higuchi, Yoshiharu; Hirotani, Shinichi; Kashiwase, Kazunori; Nakayama, Hiroyuki; Hikoso, Shungo; Takeda, Toshihiro; Watanabe, Tetsuya; Asahi, Michio; Taniike, Masayuki; Matsumura, Yasushi; Tsujimoto, Ikuko; Hongo, Kenichi; Kusakari, Yoichiro; Kurihara, Satoshi; Nishida, Kazuhiko; Ichijo, Hidenori; Hori, Masatsugu; Otsu, Kinya

2003-01-01

Left ventricular remodeling that occurs after myocardial infarction (MI) and pressure overload is generally accepted as a determinant of the clinical course of heart failure. The molecular mechanism of this process, however, remains to be elucidated. Apoptosis signal-regulating kinase 1 (ASK1) is a mitogen-activated protein kinase kinase kinase that plays an important role in stress-induced apoptosis. We used ASK1 knockout mice (ASK-/-) to test the hypothesis that ASK1 is involved in development of left ventricular remodeling. ASK-/- hearts showed no morphological or histological defects. Echocardiography and cardiac catheterization revealed normal global structure and function. Left ventricular structural and functional remodeling were determined 4 weeks after coronary artery ligation or thoracic transverse aortic constriction (TAC). ASK-/- had significantly smaller increases in left ventricular end-diastolic and end-systolic ventricular dimensions and smaller decreases in fractional shortening in both experimental models compared with WT mice. The number of terminal deoxynucleotidyl transferase biotin-dUDP nick end-labeling-positive myocytes after MI or TAC was decreased in ASK-/- compared with that in WT mice. Overexpression of a constitutively active mutant of ASK1 induced apoptosis in isolated rat neonatal cardiomyocytes, whereas neonatal ASK-/- cardiomyocytes were resistant to H2O2-induced apoptosis. An in vitro kinase assay showed increased ASK1 activity in heart after MI or TAC in WT mice. Thus, ASK1 plays an important role in regulating left ventricular remodeling by promoting apoptosis. PMID:14665690

Node and midline defects are associated with left-right development in Delta1 mutant embryos.

PubMed

Przemeck, Gerhard K H; Heinzmann, Ulrich; Beckers, Johannes; Hrabé de Angelis, Martin

2003-01-01

Axes formation is a fundamental process of early embryonic development. In addition to the anteroposterior and dorsoventral axes, the determination of the left-right axis is crucial for the proper morphogenesis of internal organs and is evolutionarily conserved in vertebrates. Genes known to be required for the normal establishment and/or maintenance of left-right asymmetry in vertebrates include, for example, components of the TGF-beta family of intercellular signalling molecules and genes required for node and midline function. We report that Notch signalling, which previously had not been implicated in this morphogenetic process, is required for normal left-right determination in mice. We show, that the loss-of-function of the delta 1 (Dll1) gene causes a situs ambiguous phenotype, including randomisation of the direction of heart looping and embryonic turning. The most probable cause for this left-right defect in Dll1 mutant embryos is a failure in the development of proper midline structures. These originate from the node, which is disrupted and deformed in Dll1 mutant embryos. Based on expression analysis in wild-type and mutant embryos, we suggest a model, in which Notch signalling is required for the proper differentiation of node cells and node morphology.

Four-phase or two-phase signal plan? A study on four-leg intersection by cellular automaton simulations

NASA Astrophysics Data System (ADS)

Jin, Cheng-Jie; Wang, Wei; Jiang, Rui

2016-08-01

The proper setting of traffic signals at signalized intersections is one of the most important tasks in traffic control and management. This paper has evaluated the four-phase traffic signal plans at a four-leg intersection via cellular automaton simulations. Each leg consists of three lanes, an exclusive left-turn lane, a through lane, and a through/right-turn lane. For a comparison, we also evaluate the two-phase signal plan. The diagram of the intersection states in the space of inflow rate versus turning ratio has been presented, which exhibits four regions: In region I/II/III, congestion will propagate upstream and laterally and result in queue spillover with both signal plans/two-phase signal plan/four-phase signal plan, respectively. Therefore, neither signal plan works in region I, and only the four-phase signal plan/two-phase signal plan works in region II/III. In region IV, both signal plans work, but two-phase signal plan performs better in terms of average delays of vehicles. Finally, we study the diagram of the intersection states and average delays in the asymmetrical configurations.

Comparative analysis of brain EEG signals generated from the right and left hand while writing

NASA Astrophysics Data System (ADS)

Sardesai, Neha; Jamali Mahabadi, S. E.; Meng, Qinglei; Choa, Fow-Sen

2016-05-01

This paper provides a comparative analysis of right handed people and left handed people when they write with both their hands. Two left handed and one right handed subject were asked to write their respective names on a paper using both, their left and right handed, and their brain signals were measured using EEG. Similarly, they were asked to perform simple mathematical calculations using both their hand. The data collected from the EEG from writing with both hands is compared. It is observed that though it is expected that the right brain only would contribute to left handed writing and vice versa, it is not so. When a right handed person writes with his/her left hand, the initial instinct is to go for writing with the right hand. Hence, both parts of the brain are active when a subject writes with the other hand. However, when the activity is repeated, the brain learns to expect to write with the other hand as the activity is repeated and then only the expected part of the brain is active.

FGF signaling is required for brain left-right asymmetry and brain midline formation.

PubMed

Neugebauer, Judith M; Yost, H Joseph

2014-02-01

Early disruption of FGF signaling alters left-right (LR) asymmetry throughout the embryo. Here we uncover a role for FGF signaling that specifically disrupts brain asymmetry, independent of normal lateral plate mesoderm (LPM) asymmetry. When FGF signaling is inhibited during mid-somitogenesis, asymmetrically expressed LPM markers southpaw and lefty2 are not affected. However, asymmetrically expressed brain markers lefty1 and cyclops become bilateral. We show that FGF signaling controls expression of six3b and six7, two transcription factors required for repression of asymmetric lefty1 in the brain. We found that Z0-1, atypical PKC (aPKC) and β-catenin protein distribution revealed a midline structure in the forebrain that is dependent on a balance of FGF signaling. Ectopic activation of FGF signaling leads to overexpression of six3b, loss of organized midline adherins junctions and bilateral loss of lefty1 expression. Reducing FGF signaling leads to a reduction in six3b and six7 expression, an increase in cell boundary formation in the brain midline, and bilateral expression of lefty1. Together, these results suggest a novel role for FGF signaling in the brain to control LR asymmetry, six transcription factor expressions, and a midline barrier structure. Copyright © 2013 Elsevier Inc. All rights reserved.

FGF Signaling is Required for Brain Left-Right Asymmetry and Brain Midline Formation

PubMed Central

Neugebauer, Judith M.; Yost, H. Joseph

2014-01-01

Early disruption of FGF signaling alters left-right (LR) asymmetry throughout the embryo. Here we uncover a role for FGF signaling that specifically disrupts brain asymmetry, independent of normal lateral plate mesoderm (LPM) asymmetry. When FGF signaling is inhibited during mid-somitogenesis, asymmetrically expressed LPM markers southpaw and lefty2 are not affected. However, asymmetrically expressed brain markers lefty1 and cyclops become bilateral. We show that FGF signaling controls expression of six3b and six7, two transcription factors required for repression of asymmetric lefty1 in the brain. We found that Z0-1, atypical PKC (aPKC) and β-catenin protein distribution revealed a midline structure in the forebrain that is dependent on a balance of FGF signaling. Ectopic activation of FGF signaling leads to overexpression of six3b, loss of organized midline adherins junctions and bilateral loss of lefty1 expression. Reducing FGF signaling leads to a reduction in six3b and six7 expression, an increase in cell boundary formation in the brain midline, and bilateral expression of lefty1. Together, these results suggest a novel role for FGF signaling in the brain to control LR asymmetry, six transcription factor expression, and a midline barrier structure. PMID:24333178

Perceived positive teacher-student relationship as a protective factor for Chinese left-behind children's emotional and behavioural adjustment.

PubMed

Liu, Yan; Li, Xiaowei; Chen, Li; Qu, Zhiyong

2015-10-01

Using cross-sectional data collected in rural communities of two provinces of China, this study examined the protective role of perceived positive teacher-student relationship for Chinese left-behind children. The participants included 1442 children with a mean age of 14.13 classified into two groups: a left-behind group (104 boys and 110 girls) and a comparison group (588 boys and 640 girls). Self-reported questionnaires concerning self-esteem, depression, problem behaviours and the teacher-student relationship were administered. Relative to the comparison group, after controlling for age, gender and family socioeconomic status, the left-behind group was disadvantaged in terms of self-esteem and depression but not in problem behaviours. As hypothesised, the results of regression analyses indicated that teacher-student relationship positively predicted self-esteem and negatively predicted depression and problem behaviours for both groups. Moreover, the association between teacher-student relationship and depression was stronger among the left-behind group, suggesting that left-behind children were more responsive to the positive effect of a desired teacher-student relationship. Taken together, the results of our study support the idea that perceived positive teacher-student relationship may serve as a protective factor for left-behind children. Practical implications and limitations of the present study are discussed. © 2014 International Union of Psychological Science.

Mycobacterium indicus pranii (MIP) mediated host protective intracellular mechanisms against tuberculosis infection: Involvement of TLR-4 mediated signaling.

PubMed

Das, Shibali; Chowdhury, Bidisha Paul; Goswami, Avranil; Parveen, Shabina; Jawed, Junaid; Pal, Nishith; Majumdar, Subrata

2016-12-01

Mycobacterium tuberculosis infection inflicts the disease Tuberculosis (TB), which is fatal if left untreated. During M. tuberculosis infection, the pathogen modulates TLR-4 receptor down-stream signaling, indicating the possible involvement of TLR-4 in the regulation of the host immune response. Mycobacterium indicus pranii (MIP) possesses immuno-modulatory properties which induces the pro-inflammatory responses via induction of TLR-4-mediated signaling. Here, we observed the immunomodulatory properties of MIP against tuberculosis infection. We have studied the detailed signaling mechanisms employed by MIP in order to restore the host immune response against the in vitro tuberculosis infection. We observed that in infected macrophages MIP treatment significantly increased the TLR-4 expression as well as activation of its downstream signaling, facilitating the activation of P38 MAP kinase. MIP treatment was able to activate NF-κB via involvement of TLR-4 signaling leading to the enhanced pro-inflammatory cytokine and NO generation in the infected macrophages and generation of protective immune response. Therefore, we may suggest that, TLR4 may represent a novel therapeutic target for the activation of the innate immune response during Tuberculosis infection. Copyright © 2016. Published by Elsevier Ltd.

P-glycoprotein (ABCB1) inhibited network of mitochondrion transport along microtubule and BMP signal-induced cell shape in chimpanzee left cerebrum by systems-theoretical analysis.

PubMed

Lin, Hong; Wang, Lin; Jiang, Minghu; Huang, Juxiang; Qi, Lianxiu

2012-10-01

We constructed the significant low-expression P-glycoprotein (ABCB1) inhibited transport and signal network in chimpanzee compared with high-expression (fold change ≥2) the human left cerebrum in GEO data set, by using integration of gene regulatory activated and inhibited network inference method with gene ontology (GO) analysis. Our result showed that ABCB1 transport and signal upstream network RAB2A inhibited ABCB1, and downstream ABCB1-inhibited SMAD1_2, NCK2, SLC25A46, GDF10, RASGRP1, EGFR, LRPPRC, RASSF2, RASA4, CA2, CBLB, UBR5, SLC25A16, ITGB3BP, DDIT4, PDPN, RAB2A in chimpanzee left cerebrum. We obtained that the different biological processes of ABCB1 inhibited transport and signal network repressed carbon dioxide transport, ER to Golgi vesicle-mediated transport, folic acid transport, mitochondrion transport along microtubule, water transport, BMP signaling pathway, Ras protein signal transduction, transforming growth factor beta receptor signaling pathway in chimpanzee compared with the inhibited network of the human left cerebrum, as a result of inducing inhibition of mitochondrion transport along microtubule and BMP signal-induced cell shape in chimpanzee left cerebrum. Our hypothesis was verified by the same and different biological processes of ABCB1 inhibited transport and signal network of chimpanzee compared with the corresponding activated network of chimpanzee and the human left cerebrum, respectively. Copyright © 2012 John Wiley & Sons, Ltd.

When Is It My Turn To Speak?

ERIC Educational Resources Information Center

Orestrom, Bengt

A study analyzed four dyadic conversations for evidence of the signals operating in the turn-taking process and facilitating the smooth exchange of turns. It found over 20 syntactic, prosodic, and semantic features occurring frequently with turn-taking. The five most significant factors correlating with turn-taking were a prosodically completed…

Head-turning asymmetries during kissing and their association with lateral preference.

PubMed

Ocklenburg, Sebastian; Güntürkün, Onur

2009-01-01

A head-turning bias to the right side is one of the earliest functional asymmetries in human development and is already present during the final weeks of gestation. To test whether head-turning preference is related to other lateral preferences in adults, kissing behaviour of participants towards a symmetrical doll was observed to assess their spontaneous head-turning preference. Additionally, participants' individual handedness, footedness, and eye preference were determined using questionnaires. A significant difference in handedness and footedness, but not eye preference, was found between left- and right-kissers, with right-kissers showing a stronger right-sided bias than left-kissers. These results support the assumption that the head-turning bias in humans may be able to induce or enhance other asymmetries of perception and action.

Protective Effect of Unacylated Ghrelin on Compression-Induced Skeletal Muscle Injury Mediated by SIRT1-Signaling

PubMed Central

Ugwu, Felix N.; Yu, Angus P.; Sin, Thomas K.; Tam, Bjorn T.; Lai, Christopher W.; Wong, S. C.; Siu, Parco M.

2017-01-01

Unacylated ghrelin, the predominant form of circulating ghrelin, protects myotubes from cell death, which is a known attribute of pressure ulcers. In this study, we investigated whether unacylated ghrelin protects skeletal muscle from pressure-induced deep tissue injury by abolishing necroptosis and apoptosis signaling and whether these effects were mediated by SIRT1 pathway. Fifteen adult Sprague Dawley rats were assigned to receive saline or unacylated ghrelin with or without EX527 (a SIRT1 inhibitor). Animals underwent two 6-h compression cycles with 100 mmHg static pressure applied over the mid-tibialis region of the right limb whereas the left uncompressed limb served as the intra-animal control. Muscle tissues underneath the compression region, and at the similar region of the opposite uncompressed limb, were collected for analysis. Unacylated ghrelin attenuated the compression-induced muscle pathohistological alterations including rounding contour of myofibers, extensive nucleus accumulation in the interstitial space, and increased interstitial space. Unacylated ghrelin abolished the increase in necroptosis proteins including RIP1 and RIP3 and attenuated the elevation of apoptotic proteins including p53, Bax, and AIF in the compressed muscle. Furthermore, unacylated ghrelin opposed the compression-induced phosphorylation and acetylation of p65 subunit of NF-kB. The anti-apoptotic effect of unacylated ghrelin was shown by a decrease in apoptotic DNA fragmentation and terminal dUTP nick-end labeling index in the compressed muscle. The protective effects of unacylated ghrelin vanished when co-treated with EX527. Our findings demonstrated that unacylated ghrelin protected skeletal muscle from compression-induced injury. The myoprotective effects of unacylated ghrelin on pressure-induced tissue injury were associated with SIRT1 signaling. PMID:29225581

Oligodendrocyte-specific activation of PERK signaling protects mice against experimental autoimmune encephalomyelitis.

PubMed

Lin, Wensheng; Lin, Yifeng; Li, Jin; Fenstermaker, Ali G; Way, Sharon W; Clayton, Benjamin; Jamison, Stephanie; Harding, Heather P; Ron, David; Popko, Brian

2013-04-03

There is compelling evidence that oligodendrocyte apoptosis, in response to CNS inflammation, contributes significantly to the development of the demyelinating disorder multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE). Therefore, approaches designed to protect oligodendrocytes would likely have therapeutic value. Activation of pancreatic endoplasmic reticulum kinase (PERK) signaling in response to endoplasmic reticulum (ER) stress increases cell survival under various cytotoxic conditions. Moreover, there is evidence that PERK signaling is activated in oligodendrocytes within demyelinating lesions in multiple sclerosis and EAE. Our previous study demonstrated that CNS delivery of the inflammatory cytokine interferon-γ before EAE onset protected mice against EAE, and this protection was dependent on PERK signaling. In our current study, we sought to elucidate the role of PERK signaling in oligodendrocytes during EAE. We generated transgenic mice that allow for temporally controlled activation of PERK signaling, in the absence of ER stress, specifically in oligodendrocytes. We demonstrated that persistent activation of PERK signaling was not deleterious to oligodendrocyte viability or the myelin of adult animals. Importantly, we found that enhanced activation of PERK signaling specifically in oligodendrocytes significantly attenuated EAE disease severity, which was associated with reduced oligodendrocyte apoptosis, demyelination, and axonal degeneration. This effect was not the result of an altered degree of the inflammatory response in EAE mice. Our results provide direct evidence that activation of PERK signaling in oligodendrocytes is cytoprotective, protecting mice against EAE.

Driver behavior analysis for right-turn drivers at signalized intersections using SHRP 2 naturalistic driving study data.

PubMed

Wu, Jianqing; Xu, Hao

2017-12-01

Understanding driver behavior is important for traffic safety and operation, especially at intersections where different traffic movements conflict. While most driver-behavior studies are based on simulation, this paper documents the analysis of driver-behavior at signalized intersections with the SHRP 2 Naturalistic Driving Study (NDS) data. This study analyzes the different influencing factors on the operation (speed control) and observation of right-turn drivers. A total of 300 NDS trips at six signalized intersections were used, including the NDS time-series sensor data, the forward videos and driver face videos. Different factors of drivers, vehicles, roads and environments were studied for their influence on driver behavior. An influencing index function was developed and the index was calculated for each influencing factor to quantitatively describe its influencing level. The influencing index was applied to prioritize the factors, which facilitates development and selection of safety countermeasures to improve intersection safety. Drivers' speed control was analyzed under different conditions with consideration of the prioritized influencing factors. Vehicle type, traffic signal status, conflicting traffic, conflicting pedestrian and driver age group were identified as the five major influencing factors on driver observation. This research revealed that drivers have high acceleration and low observation frequency under Right-Turn-On-Red (RTOR), which constituted potential danger for other roadway users, especially for pedestrians. As speed has a direct influence on crash rates and severities, the revealed speed patterns of the different situations also benefit selection of safety countermeasures at signalized intersections. Published by Elsevier Ltd.

Protective Socket For Integrated Circuits

NASA Technical Reports Server (NTRS)

Wilkinson, Chris; Henegar, Greg

1988-01-01

Socket for intergrated circuits (IC's) protects from excessive voltages and currents or from application of voltages and currents in wrong sequence during insertion or removal. Contains built-in switch that opens as IC removed, disconnecting leads from signals and power. Also protects other components on circuit board from transients produced by insertion and removal of IC. Makes unnecessary to turn off power to entire circuit board so other circuits on board continue to function.

Left ventricular hypertrophy as protective factor after bypass grafting.

PubMed

Iannuzzi, Gian Luca; Maniscalco, Mauro; Elia, Andrea; Scognamiglio, Anna; Furgi, Giuseppe; Rengo, Franco

2018-05-01

Left ventricular hypertrophy (LVH) is a well established cardiovascular risk factor, accounting for an increase in cardiovascular morbid-mortality, although how much the magnitude and the kind of LVH could affect cardiovascular outcomes is in large part unknown. We speculate that mild LVH in absence of left ventricular (LV) chamber dilation, could play a protective role towards functional capacity, clinical outcome, cardiovascular and total morbi-mortality in conditions in which LV systolic function is generally reduced. Accordingly to many epidemiological observations, the availability of extra-quote of systolic function could lead to a significative improvement in the final outcome of some kinds of heart patients, as those undergoing bypass-grafting, where the stress for heart and cardiovascular system is always high. We suppose that the functional reserve available for patients with LVH could make the difference with respect to other patients undergoing myocardial revascularization. Similarly, the availability of a contractile reserve warranted by LVH could ensure a little gain in the outcome for patients after other major cardiovascular events (such as myocardial infarction or other heart surgery as surgical valve replacement). However, our hypothesis only involves mild LVH without LV chamber dilation, that is the initial stage of "non-dilated concentric" LVH and "non-dilated eccentric" LVH according to the new four-tiered classification of LVH based on relative wall thickness and LV dilation. Support for our hypothesis derives from the well-known protective role of systolic function that is a major factor in almost all cardiovascular diseases, where LV ejection fraction (LVEF) has shown to significantly improve quality of life, as well as morbidity and mortality. The knowledge that mild LVH in absence of LV chamber dilation is not as harmful in such conditions as believed at present could make avoidable some drugs prescription in some stages of the disease

Targeting RNS/caveolin-1/MMP signaling cascades to protect against cerebral ischemia-reperfusion injuries: potential application for drug discovery

PubMed Central

Chen, Han-sen; Chen, Xi; Li, Wen-ting; Shen, Jian-gang

2018-01-01

Reactive nitrogen species (RNS) play important roles in mediating cerebral ischemia-reperfusion injury. RNS activate multiple signaling pathways and participate in different cellular events in cerebral ischemia-reperfusion injury. Recent studies have indicated that caveolin-1 and matrix metalloproteinase (MMP) are important signaling molecules in the pathological process of ischemic brain injury. During cerebral ischemia-reperfusion, the production of nitric oxide (NO) and peroxynitrite (ONOO−), two representative RNS, down-regulates the expression of caveolin-1 (Cav-1) and, in turn, further activates nitric oxide synthase (NOS) to promote RNS generation. The increased RNS further induce MMP activation and mediate disruption of the blood-brain barrier (BBB), aggravating the brain damage in cerebral ischemia-reperfusion injury. Therefore, the feedback interaction among RNS/Cav-1/MMPs provides an amplified mechanism for aggravating ischemic brain damage during cerebral ischemia-reperfusion injury. Targeting the RNS/Cav-1/MMP pathway could be a promising therapeutic strategy for protecting against cerebral ischemia-reperfusion injury. In this mini-review article, we highlight the important role of the RNS/Cav-1/MMP signaling cascades in ischemic stroke injury and review the current progress of studies seeking therapeutic compounds targeting the RNS/Cav-1/MMP signaling cascades to attenuate cerebral ischemia-reperfusion injury. Several representative natural compounds, including calycosin-7-O-β-D-glucoside, baicalin, Momordica charantia polysaccharide (MCP), chlorogenic acid, lutein and lycopene, have shown potential for targeting the RNS/Cav-1/MMP signaling pathway to protect the brain in ischemic stroke. Therefore, the RNS/Cav-1/MMP pathway is an important therapeutic target in ischemic stroke treatment. PMID:29595191

Targeting RNS/caveolin-1/MMP signaling cascades to protect against cerebral ischemia-reperfusion injuries: potential application for drug discovery.

PubMed

Chen, Han-Sen; Chen, Xi; Li, Wen-Ting; Shen, Jian-Gang

2018-05-01

Reactive nitrogen species (RNS) play important roles in mediating cerebral ischemia-reperfusion injury. RNS activate multiple signaling pathways and participate in different cellular events in cerebral ischemia-reperfusion injury. Recent studies have indicated that caveolin-1 and matrix metalloproteinase (MMP) are important signaling molecules in the pathological process of ischemic brain injury. During cerebral ischemia-reperfusion, the production of nitric oxide (NO) and peroxynitrite (ONOO - ), two representative RNS, down-regulates the expression of caveolin-1 (Cav-1) and, in turn, further activates nitric oxide synthase (NOS) to promote RNS generation. The increased RNS further induce MMP activation and mediate disruption of the blood-brain barrier (BBB), aggravating the brain damage in cerebral ischemia-reperfusion injury. Therefore, the feedback interaction among RNS/Cav-1/MMPs provides an amplified mechanism for aggravating ischemic brain damage during cerebral ischemia-reperfusion injury. Targeting the RNS/Cav-1/MMP pathway could be a promising therapeutic strategy for protecting against cerebral ischemia-reperfusion injury. In this mini-review article, we highlight the important role of the RNS/Cav-1/MMP signaling cascades in ischemic stroke injury and review the current progress of studies seeking therapeutic compounds targeting the RNS/Cav-1/MMP signaling cascades to attenuate cerebral ischemia-reperfusion injury. Several representative natural compounds, including calycosin-7-O-β-D-glucoside, baicalin, Momordica charantia polysaccharide (MCP), chlorogenic acid, lutein and lycopene, have shown potential for targeting the RNS/Cav-1/MMP signaling pathway to protect the brain in ischemic stroke. Therefore, the RNS/Cav-1/MMP pathway is an important therapeutic target in ischemic stroke treatment.

Nodal signalling in Xenopus: the role of Xnr5 in left/right asymmetry and heart development.

PubMed

Tadjuidje, Emmanuel; Kofron, Matthew; Mir, Adnan; Wylie, Christopher; Heasman, Janet; Cha, Sang-Wook

2016-08-01

Nodal class TGF-β signalling molecules play essential roles in establishing the vertebrate body plan. In all vertebrates, nodal family members have specific waves of expression required for tissue specification and axis formation. In Xenopus laevis, six nodal genes are expressed before gastrulation, raising the question of whether they have specific roles or act redundantly with each other. Here, we examine the role of Xnr5. We find it acts at the late blastula stage as a mesoderm inducer and repressor of ectodermal gene expression, a role it shares with Vg1. However, unlike Vg1, Xnr5 depletion reduces the expression of the nodal family member xnr1 at the gastrula stage. It is also required for left/right laterality by controlling the expression of the laterality genes xnr1, antivin (lefty) and pitx2 at the tailbud stage. In Xnr5-depleted embryos, the heart field is established normally, but symmetrical reduction in Xnr5 levels causes a severely stunted midline heart, first evidenced by a reduction in cardiac troponin mRNA levels, while left-sided reduction leads to randomization of the left/right axis. This work identifies Xnr5 as the earliest step in the signalling pathway establishing normal heart laterality in Xenopus. © 2016 The Authors.

TGFβ signaling in establishing left-right asymmetry.

PubMed

Shiratori, Hidetaka; Hamada, Hiroshi

2014-08-01

Two TGFβ-related proteins, Nodal and Lefty, are asymmetrically expressed and play central roles in establishing left-right (L-R) asymmetry of our body. Nodal acts as a left-side determinant whereas Lefty restricts Nodal activity to the left side by acting as a feedback inhibitor of Nodal. While the mechanism for symmetry breaking is variable among animals, the pair of Nodal and Lefty has a conserved role in the L-R asymmetry pathway. Function and regulation of Nodal and Lefty have been revealed in the last decades, but in this review we summarize the role of TGFβ-related proteins together with more recent findings. We mainly discuss observations made with mouse embryos, unless indicated otherwise. Copyright © 2014. Published by Elsevier Ltd.

Turning off artistic ability: the influence of left DBS in art production.

PubMed

Drago, V; Foster, P S; Okun, M S; Cosentino, F I I; Conigliaro, R; Haq, I; Sudhyadhom, A; Skidmore, F M; Heilman, K M

2009-06-15

The influence of Parkinson's disease (PD) as well as deep brain stimulation (DBS) on visual-artistic production of people who have been artists is unclear. We systematically assessed the artistic-creative productions of a patient with PD who was referred to us for management of a left subthalamic region (STN) DBS. The patient was an artist before her disease started, permitting us to analyze changes in her artistic-creative production over the course of the illness and during her treatment with DBS. We collected her paintings from four time periods: Time 1 (Early Pre-Presymptomatic), Time 2 (Later Presymptomatic), Time 3 (Symptomatic), and Time 4 (DBS Symptomatic). A total of 59 paintings were submitted to a panel of judges, who rated the paintings on 6 different artistic qualities including: aesthetics, closure, evocative impact, novelty, representation, technique. Aesthetics and evocative impact significantly declined from Time 2 to Time 4. Representation and technique indicated a curvilinear relationship, with initial improvement from Time 1 to Time 2 followed by a decline from Time 2 to Time 4. These results suggest that left STN/SNR-DBS impacted artistic performances in our patient. The reason for these alterations is not known, but it might be that alterations of left hemisphere functions induce a hemispheric bias reducing the influence the right hemisphere which is important for artistic creativity. The left hemisphere itself plays a critical role in artistic creativity and DBS might have altered left hemisphere functions or altered the mesolimbic system which might have also influenced creativity. Future studies will be required to learn how PD and DBS influence creativity.

Effective measures to restrict vehicle turning movements.

DOT National Transportation Integrated Search

2015-12-01

This study evaluated alternatives to raised/non-traversable medians on driveways and approaches. : Raised medians are often considered as an effective technique to limit direct left-turns that may be due : to a significant number of conflict points. ...

An Ultra-Low Power Turning Angle Based Biomedical Signal Compression Engine with Adaptive Threshold Tuning.

PubMed

Zhou, Jun; Wang, Chao

2017-08-06

Intelligent sensing is drastically changing our everyday life including healthcare by biomedical signal monitoring, collection, and analytics. However, long-term healthcare monitoring generates tremendous data volume and demands significant wireless transmission power, which imposes a big challenge for wearable healthcare sensors usually powered by batteries. Efficient compression engine design to reduce wireless transmission data rate with ultra-low power consumption is essential for wearable miniaturized healthcare sensor systems. This paper presents an ultra-low power biomedical signal compression engine for healthcare data sensing and analytics in the era of big data and sensor intelligence. It extracts the feature points of the biomedical signal by window-based turning angle detection. The proposed approach has low complexity and thus low power consumption while achieving a large compression ratio (CR) and good quality of reconstructed signal. Near-threshold design technique is adopted to further reduce the power consumption on the circuit level. Besides, the angle threshold for compression can be adaptively tuned according to the error between the original signal and reconstructed signal to address the variation of signal characteristics from person to person or from channel to channel to meet the required signal quality with optimal CR. For demonstration, the proposed biomedical compression engine has been used and evaluated for ECG compression. It achieves an average (CR) of 71.08% and percentage root-mean-square difference (PRD) of 5.87% while consuming only 39 nW. Compared to several state-of-the-art ECG compression engines, the proposed design has significantly lower power consumption while achieving similar CRD and PRD, making it suitable for long-term wearable miniaturized sensor systems to sense and collect healthcare data for remote data analytics.

Association between glutamate/glutamine and blood oxygen level dependent signal in the left dorsolateral prefrontal region during verbal working memory.

PubMed

Vijayakumari, Anupa A; Thomas, Bejoy; Menon, Ramshekhar N; Kesavadas, Chandrasekharan

2018-04-11

Functional MRI (fMRI) has provided much insight into the changes in the neuronal activity on the basis of blood oxygen level dependent (BOLD) phenomenon. The dynamic changes in the metabolites can be detected using functional proton magnetic resonance spectroscopy (H-fMRS). The strategy of combining fMRI and H-fMRS would facilitate the understanding of the neurochemical interpretation of the BOLD signal. The dorsolateral prefrontal region is critically involved in the processing of working memory (WM), as demonstrated by the studies involving the neuroimaging, neuropsychological, and electrophysiological experiments. In this study, we tested the association between BOLD signal and changes in brain metabolites in the left dorsolateral prefrontal region using N-back verbal WM task. We used single-voxel task-based H-MRS acquired in the left dorsolateral prefrontal region and fMRI during the performance of N-back verbal WM task to investigate the association between changes in metabolites and BOLD response in 10 healthy participants. The correlation between changes in metabolites and percent signal change was examined by the Pearson correlation. The Pearson correlation analysis revealed a significant positive correlation between the BOLD signal and glutamate/glutamine in the left dorsolateral prefrontal region during the verbal WM. Our finding suggests that glutamate/glutamine cycle plays a critical role in the neuronal activation as reflected by the changes in the BOLD response.

iPSC-derived cardiomyocytes reveal abnormal TGFβ signaling in left ventricular non-compaction cardiomyopathy

PubMed Central

Kodo, Kazuki; Ong, Sang-Ging; Jahanbani, Fereshteh; Termglinchan, Vittavat; Hirono, Keiichi; InanlooRahatloo, Kolsoum; Ebert, Antje D.; Shukla, Praveen; Abilez, Oscar J.; Churko, Jared M.; Karakikes, Ioannis; Jung, Gwanghyun; Ichida, Fukiko; Wu, Sean M.; Snyder, Michael P.; Bernstein, Daniel; Wu, Joseph C.

2016-01-01

Left ventricular non-compaction (LVNC) is the third most prevalent cardiomyopathy in children and its pathogenesis has been associated with the developmental defect of the embryonic myocardium. We show that patient-specific induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) generated from LVNC patients carrying a mutation in the cardiac transcription factor TBX20 recapitulate a key aspect of the pathological phenotype at the single-cell level and was associated with perturbed transforming growth factor beta (TGFβ) signaling. LVNC iPSC-CMs have decreased proliferative capacity due to abnormal activation of TGFβ signaling. TBX20 regulates the expression of TGFβ signaling modifiers including a known genetic cause of LVNC, PRDM16, and genome editing of PRDM16 caused proliferation defects in iPSC-CMs. Inhibition of TGFβ signaling and genome correction of the TBX20 mutation were sufficient to reverse the disease phenotype. Our study demonstrates that iPSC-CMs are a useful tool for the exploration of pathological mechanisms underlying poorly understood cardiomyopathies including LVNC. PMID:27642787

An Ultra-Low Power Turning Angle Based Biomedical Signal Compression Engine with Adaptive Threshold Tuning

PubMed Central

Zhou, Jun; Wang, Chao

2017-01-01

Intelligent sensing is drastically changing our everyday life including healthcare by biomedical signal monitoring, collection, and analytics. However, long-term healthcare monitoring generates tremendous data volume and demands significant wireless transmission power, which imposes a big challenge for wearable healthcare sensors usually powered by batteries. Efficient compression engine design to reduce wireless transmission data rate with ultra-low power consumption is essential for wearable miniaturized healthcare sensor systems. This paper presents an ultra-low power biomedical signal compression engine for healthcare data sensing and analytics in the era of big data and sensor intelligence. It extracts the feature points of the biomedical signal by window-based turning angle detection. The proposed approach has low complexity and thus low power consumption while achieving a large compression ratio (CR) and good quality of reconstructed signal. Near-threshold design technique is adopted to further reduce the power consumption on the circuit level. Besides, the angle threshold for compression can be adaptively tuned according to the error between the original signal and reconstructed signal to address the variation of signal characteristics from person to person or from channel to channel to meet the required signal quality with optimal CR. For demonstration, the proposed biomedical compression engine has been used and evaluated for ECG compression. It achieves an average (CR) of 71.08% and percentage root-mean-square difference (PRD) of 5.87% while consuming only 39 nW. Compared to several state-of-the-art ECG compression engines, the proposed design has significantly lower power consumption while achieving similar CRD and PRD, making it suitable for long-term wearable miniaturized sensor systems to sense and collect healthcare data for remote data analytics. PMID:28783079

Pedestrian Safety Treatments for Signalized Intersections : Training Course Development

DOT National Transportation Integrated Search

2017-11-01

When drivers make left turns during a permissive turn phase, they must yield to pedestrians as well as oncoming through vehicles. Left-turning drivers sometimes overlook pedestrians in the crosswalk while watching the opposing intersection approach. ...

Mineralocorticoid receptor antagonists modulate galectin-3 and interleukin-33/ST2 signaling in left ventricular systolic dysfunction after acute myocardial infarction.

PubMed

Lax, Antonio; Sanchez-Mas, Jesus; Asensio-Lopez, Maria C; Fernandez-Del Palacio, Maria J; Caballero, Luis; Garrido, Iris P; Pastor-Perez, Francisco J; Januzzi, James L; Pascual-Figal, Domingo A

2015-01-01

This study aimed to evaluate the specific role of the 2 available mineralocorticoid receptor antagonists (MRAs), eplerenone and spironolactone, on the modulation of galectin-3 (Gal-3) and interleukin (IL)-33/ST2 signaling in an experimental model of left ventricular systolic dysfunction after acute myocardial infarction (MI). The molecular mechanisms of benefits of MRAs in patients with left ventricular systolic dysfunction after MI not well understood. MI and left ventricular systolic dysfunction were induced by permanent ligation of the anterior coronary artery in 45 male Wistar rats, randomly assigned to no therapy (MI group, n = 15) or to receive MRAs (100 mg/kg/day) for 4 weeks; either eplerenone (n = 15) or spironolactone (n = 15) was used. A sham group was used as a control (n = 8). Elements of the pathway for Gal-3 including transforming growth factor (TGF)-β and SMAD3, as well as that for IL-33/ST2 (including IL-33 and soluble ST2 [sST2]) were analyzed in the infarcted and noninfarcted myocardium by quantitative real-time reverse transcription polymerase chain reaction. Expression of markers of fibrosis (collagen types I and III, tissue inhibitor of metalloproteinase-1) and inflammation (IL-6, tumor necrosis factor-α, monocyte chemotactic protein-1) was also examined. In the infarcted myocardium, compared with sham animals, the MI group had higher concentrations of Gal-3, TGF-β, SMAD3, IL-33, and sST2, as well as higher concentrations of markers of fibrosis and inflammation. Treatment with MRAs down-regulated Gal-3, TGF-β, and SMAD3 and enhanced IL-33/ST2 signaling with lower expression of sST2; protective IL-33 up-regulation was unaffected by MRAs. Modulation of Gal-3 and IL-33/ST2 signaling induced by MRAs correlated with lower expression levels of fibrosis and inflammatory markers. No differences were found between eplerenone and spironolactone. In the noninfarcted myocardium, compared with sham animals, the MI group exhibited a higher expression of

Hydrogen-rich medium protects mouse embryonic fibroblasts from oxidative stress by activating LKB1-AMPK-FoxO1 signal pathway.

PubMed

Lee, Jihyun; Yang, Goowon; Kim, Young-Joo; Tran, Quynh Hoa; Choe, Wonchae; Kang, Insug; Kim, Sung Soo; Ha, Joohun

2017-09-23

Persistent oxidative stress is recognized as a major cause of many pathological conditions as well as ageing. However, most clinical trials of dietary antioxidants have failed to produce successful outcomes in treating oxidative stress-induced diseases. Molecular hydrogen (H 2 ) has recently received considerable attention as a therapeutic agent owing to its novel antioxidant properties, a selective scavenger of hydroxyl and peroxynitrite radicals. Beyond this, numerous reports support that H 2 can modulate the activity of various cellular signal pathways. However, its effect on AMP-activated protein kinase (AMPK) signal pathway, a central regulator of energy hemostasis, has remained almost elusive. Here, we report that hydrogen-rich medium activated LKB1-AMPK signal pathway without ATP depletion, which in turn induced FoxO1-dependent transcription of manganese superoxide dismutase and catalase in mouse embryonic fibroblasts. Moreover, hydrogen-rich media effectively reduced the level of reactive oxygen species in cells treated with hydrogen peroxide and protected these cells from apoptosis in an AMPK-dependent manner. These results suggest that the LKB1-AMPK-FoxO1 signaling pathway is a critical mediator of the antioxidant properties of H 2 , further supporting the idea that H 2 acts as a signaling molecule to serve various physiological functions. Copyright © 2017 Elsevier Inc. All rights reserved.

Protective effect of tanshinone IIA against cardiac hypertrophy in spontaneously hypertensive rats through inhibiting the Cys-C/Wnt signaling pathway

PubMed Central

Feng, Jun; Chen, Hua-Wen; Pi, Li-Juan; Wang, Jin; Zhan, Da-Qian

2017-01-01

The study aimed to investigate the protective effect of tanshinone IIA against cardiac hypertrophy in spontaneously hypertensive rats (SHRs) through the Cys-C/Wnt signaling pathway. Thirty SHRs were randomly divided into cardiac hypertrophy, low- and high-dose tanshinone IIA groups. Ten Wistar-Kyoto rats were selected as control group. The systolic blood pressure (SBP), heart weight (HW), left ventricular weight (LVW) and body weight (BW) of all rats were recorded. HE staining and qRT-PCR were applied to observe the morphology of myocardial tissue and mRNA expressions of COL1A1 and COL3A1. ELISA and Western blotting were used to measure the serum asymmetric dimethylarginine (ADMA), nitric oxide (NO) and cardiac troponin I (cTnI) levels, and the expressions of the Cys-C/Wnt signaling pathway-related proteins, eNOS and Nox4. Compared with the cardiac hypertrophy group, the SBP, HW/BW, LVW/BW, swelling degree of myocardial cells, COL1A1 and COL3A1 mRNA expressions, serum cTnI and ADMA levels, and the Cys-C/Wnt signaling pathway-related proteins and Nox4 expressions in the low- and high-dose tanshinone IIA groups were decreased, but the endothelial NO synthase (eNOS), phosphorylated eNOS (Ser1177) and NO expressions were increased. No significant difference was found between the low- and high-dose tanshinone IIA groups. Our study indicated a protective effect of tanshinone IIA against cardiac hypertrophy in SHRs through inhibiting the Cys-C/Wnt signaling pathway. PMID:28053285

Maintenance of valvular integrity with Impella left heart support: Results from the multicenter PROTECT II randomized study.

PubMed

Goldstein, James A; Dixon, Simon R; Douglas, Pamela S; Ohman, E Magnus; Moses, Jeffrey; Popma, Jeffrey J; O'Neill, William W

2017-10-08

The Impella 2.5 axial flow pump, which is positioned across the aortic valve, is widely employed for hemodynamic support. The present study compared structural and functional integrity of the left heart valves in patients undergoing Impella vs intra-aortic balloon pump in the randomized PROTECT II trial. Transthoracic echocardiograms were performed at baseline, 1 and 3 months in 445 patients in the PROTECT II trial. Serial studies were analyzed by an independent echocardiography core laboratory for aortic and mitral valve structure and function, and left ventricular ejection fraction (LVEF). During Impella support there was no appreciable change in the degree of baseline valvular regurgitation. There were no cases of structural derangement of the mitral or aortic valve after use of the Impella device. At 90-day follow-up, there was an average 22% relative increase in LVEF from baseline (27% ± 9 vs. 33% ± 11, P < 0.001). The present echocardiographic analysis of the PROTECT II study confirms prior observations regarding the safety of the Impella 2.5 device with respect to mitral and aortic valve function. © 2017 Wiley Periodicals, Inc.

Effects of a continuous lateral turning device on pressure relief.

PubMed

Do, Nam Ho; Kim, Deog Young; Kim, Jung-Hoon; Choi, Jong Hyun; Joo, So Young; Kang, Na Kyung; Baek, Yoon Su

2016-01-01

[Purpose] The purpose of this study was to examine the pressure-relieving effects of a continuous lateral turning device on common pressure ulcer sites. [Subjects] Twenty-four healthy adults participated. [Methods] The design of our continuous lateral turning device was motivated by the need for an adequate pressure-relieving device for immobile and/or elderly people. The procedure of manual repositioning is embodied in our continuous lateral turning device. The interface pressure and time were measured, and comfort grade was evaluated during sessions of continuous lateral turning at 0°, 15°, 30°, and 45°. We quantified the pressure-relieving effect using peak pressure, mean pressure, and pressure time integration. [Results] Participants demonstrated pressure time integration values below the pressure-time threshold at 15°, 30°, and 45° at all the common pressure ulcer sites. Moreover, the most effective angles for pressure relief at the common pressure ulcer sites were 30° at the occiput, 15° at the left scapula, 45° at the right scapula, 45° at the sacrum, 15° at the right heel, and 30° at the left heel. However, angles greater than 30° induced discomfort. [Conclusion] Continuous lateral turning with our specially designed device effectively relieved the pressure of targeted sites. Moreover, the suggested angles of continuous lateral turning can be used to relieve pressure at targeted sites.

A real-time traffic control method for the intersection with pre-signals under the phase swap sorting strategy

PubMed Central

Bie, Yiming; Wang, Yinhai

2017-01-01

To deal with the conflicts between left-turn and through traffic streams and increase the discharge capacity, this paper addresses the pre-signal which is implemented at a signalized intersection. Such an intersection with pre-signal is termed as a tandem intersection. For the tandem intersection, phase swap sorting strategy is deemed as the most effective phasing scheme in view of some exclusive merits, such as easier compliance of drivers, and shorter sorting area. However, a major limitation of the phase swap sorting strategy is not considered in previous studies: if one or more vehicle is left at the sorting area after the signal light turns to red, the capacity of the approach would be dramatically dropped. Besides, previous signal control studies deal with a fixed timing plan that is not adaptive with the fluctuation of traffic flows. Therefore, to cope with these two gaps, this paper firstly takes an in-depth analysis of the traffic flow operations at the tandem intersection. Secondly, three groups of loop detectors are placed to obtain the real-time vehicle information for adaptive signalization. The lane selection behavior in the sorting area is considered to set the green time for intersection signals. With the objective of minimizing the vehicle delay, the signal control parameters are then optimized based on a dynamic programming method. Finally, numerical experiments show that average vehicle delay and maximum queue length can be reduced under all scenarios. PMID:28531198

A real-time traffic control method for the intersection with pre-signals under the phase swap sorting strategy.

PubMed

Bie, Yiming; Liu, Zhiyuan; Wang, Yinhai

2017-01-01

To deal with the conflicts between left-turn and through traffic streams and increase the discharge capacity, this paper addresses the pre-signal which is implemented at a signalized intersection. Such an intersection with pre-signal is termed as a tandem intersection. For the tandem intersection, phase swap sorting strategy is deemed as the most effective phasing scheme in view of some exclusive merits, such as easier compliance of drivers, and shorter sorting area. However, a major limitation of the phase swap sorting strategy is not considered in previous studies: if one or more vehicle is left at the sorting area after the signal light turns to red, the capacity of the approach would be dramatically dropped. Besides, previous signal control studies deal with a fixed timing plan that is not adaptive with the fluctuation of traffic flows. Therefore, to cope with these two gaps, this paper firstly takes an in-depth analysis of the traffic flow operations at the tandem intersection. Secondly, three groups of loop detectors are placed to obtain the real-time vehicle information for adaptive signalization. The lane selection behavior in the sorting area is considered to set the green time for intersection signals. With the objective of minimizing the vehicle delay, the signal control parameters are then optimized based on a dynamic programming method. Finally, numerical experiments show that average vehicle delay and maximum queue length can be reduced under all scenarios.

Safety impact of permitting right-turn-on-red : a report to Congress

DOT National Transportation Integrated Search

1994-12-01

The Energy Policy Act of 1992 required NHTSA to conduct a study of the safety impact of permitting right and left turns on red lights. The report presents a brief summary of the current status of State implementation of laws permitting right and left...

Signaling epicenters: The role of caveolae and caveolins in volatile anesthetic induced cardiac protection

PubMed Central

Horikawa, Yousuke T.; Tsutsumi, Yasuo M.; Patel, Hemal H.; Roth, David M.

2014-01-01

Caveolae are flask-like invaginations of the cell surface that have been identified as signaling epicenters. Within these microdomains, caveolins are structural proteins of caveolae, which are able to interact with numerous signaling molecules affecting temporal and spatial dimensions required in cardiac protection. This complex moiety is essential to the mechanisms involved in volatile anesthetics. In this review, we will outline a general overview of caveolae and caveolins and their role in protective signaling, with a focus on the effects of volatile anesthetics. These recent developments have allowed us to better understand the mechanistic effect of volatile anesthetics and their potential in cardiac protection. PMID:24502576

A UV-B-specific signaling component orchestrates plant UV protection

PubMed Central

Brown, Bobby A.; Cloix, Catherine; Jiang, Guang Huai; Kaiserli, Eirini; Herzyk, Pawel; Kliebenstein, Daniel J.; Jenkins, Gareth I.

2005-01-01

UV-B radiation in sunlight has diverse effects on humans, animals, plants, and microorganisms. UV-B can cause damage to molecules and cells, and consequently organisms need to protect against and repair UV damage to survive in sunlight. In plants, low nondamaging levels of UV-B stimulate transcription of genes involved in UV-protective responses. However, remarkably little is known about the underlying mechanisms of UV-B perception and signal transduction. Here we report that Arabidopsis UV RESISTANCE LOCUS 8 (UVR8) is a UV-B-specific signaling component that orchestrates expression of a range of genes with vital UV-protective functions. Moreover, we show that UVR8 regulates expression of the transcription factor HY5 specifically when the plant is exposed to UV-B. We demonstrate that HY5 is a key effector of the UVR8 pathway, and that it is required for survival under UV-B radiation. UVR8 has sequence similarity to the eukaryotic guanine nucleotide exchange factor RCC1, but we found that it has little exchange activity. However, UVR8, like RCC1, is located principally in the nucleus and associates with chromatin via histones. Chromatin immunoprecipitation showed that UVR8 associates with chromatin in the HY5 promoter region, providing a mechanistic basis for its involvement in regulating transcription. We conclude that UVR8 defines a UV-B-specific signaling pathway in plants that orchestrates the protective gene expression responses to UV-B required for plant survival in sunlight. PMID:16330762

Delta-Tocotrienol: Radiation Protection and Effects on Signal Transduction Pathways

DTIC Science & Technology

2011-06-15

Delta- Tocotrienol : Radiation Protection and Effects on Signal Transduction Pathways Venkataraman Srinivasan, PhD Mang Xiao, MD Principal...2011 2. REPORT TYPE 3. DATES COVERED 00-00-2011 to 00-00-2011 4. TITLE AND SUBTITLE Delta- Tocotrienol : Radiation Protection And Effects On...Mechanisms? 17 Survival of γ-irradiated mouse bone marrow and primary human hematopoietic CD34+ cells was significantly enhanced by Delta- tocotrienol (DT3

Advantages in exploring a new environment with the left eye in lizards.

PubMed

Bonati, Beatrice; Csermely, Davide; Sovrano, Valeria Anna

2013-07-01

Lizards (Podarcis muralis) preferentially use the left eye during spatial exploration in a binocular condition. Here we allowed 44 adult wild lizards to explore an unknown maze for 20 min under a temporary monocular condition whilst recording their movements, particularly the direction of turns made whilst walking within the maze. Lizards with a patch on their right eye, i.e. using their left eye to monitor the environment, moved faster than lizards with a patch on their left eye when turning both leftward and rightward in a T-cross. Hence, right eye-patched lizards were faster than left eye-patched lizards also in turning right, although their right eye was covered. Thus, lizards that could use the left eye/right hemisphere to attend spatial cues appeared to have more control and to be more prompt in exploring the maze. In addition, female lizards with their left eye covered stopped very frequently when they reached crosses, showing a high level of indecision. Results confirm that P. muralis lizards using their left eye only in exploring a new environment react faster and more efficiently than those using the right eye only in exploration. Hence lateralisation of spatial stimuli mediated by the left eye/right hemisphere could provide an advantage to this species. Copyright © 2013 Elsevier B.V. All rights reserved.

5-Year Outcomes After Left Atrial Appendage Closure: From the PREVAIL and PROTECT AF Trials.

PubMed

Reddy, Vivek Y; Doshi, Shephal K; Kar, Saibal; Gibson, Douglas N; Price, Matthew J; Huber, Kenneth; Horton, Rodney P; Buchbinder, Maurice; Neuzil, Petr; Gordon, Nicole T; Holmes, David R

2017-12-19

The PROTECT AF (WATCHMAN Left Atrial Appendage System for Embolic Protection in Patients With Atrial Fibrillation) trial demonstrated that left atrial appendage closure (LAAC) with the Watchman device (Boston Scientific, St. Paul, Minnesota) was equivalent to warfarin for preventing stroke in atrial fibrillation, but had a high rate of complications. In a second randomized trial, PREVAIL (Evaluation of the WATCHMAN LAA Closure Device in Patients With Atrial Fibrillation Versus Long Term Warfarin Therapy), the complication rate was low. The warfarin cohort experienced an unexpectedly low ischemic stroke rate, rendering the efficacy endpoints inconclusive. However, these outcomes were based on relatively few patients followed for a relatively short time. The final results of the PREVAIL trial, both alone and as part of a patient-level meta-analysis with the PROTECT AF trial, are reported with patients in both trials followed for 5 years. PREVAIL and PROTECT AF are prospective randomized clinical trials with patients randomized 2:1 to LAAC or warfarin; together, they enrolled 1,114 patients for 4,343 patient-years. Analyses are by intention-to-treat, and rates are events per 100 patient-years. For the PREVAIL trial, the first composite coprimary endpoint of stroke, systemic embolism (SE), or cardiovascular/unexplained death did not achieve noninferiority (posterior probability for noninferiority = 88.4%), whereas the second coprimary endpoint of post-procedure ischemic stroke/SE did achieve noninferiority (posterior probability for noninferiority = 97.5%); the warfarin arm maintained an unusually low ischemic stroke rate (0.73%). In the meta-analysis, the composite endpoint was similar between groups (hazard ratio [HR]: 0.820; p = 0.27), as were all-stroke/SE (HR: 0.961; p = 0.87). The ischemic stroke/SE rate was numerically higher with LAAC, but this difference did not reach statistical significance (HR: 1.71; p = 0.080). However, differences in

BMP signaling protects telencephalic fate by repressing eye identity and its Cxcr4-dependent morphogenesis.

PubMed

Bielen, Holger; Houart, Corinne

2012-10-16

Depletion of Wnt signaling is a major requirement for the induction of the anterior prosencephalon. However, the molecular events driving the differential regionalization of this area into eye-field and telencephalon fates are still unknown. Here we show that the BMP pathway is active in the anterior neural ectoderm during late blastula to early gastrula stage in zebrafish. Bmp2b mutants and mosaic loss-of-function experiments reveal that BMP acts as a repressor of eye-field fate through inhibition of its key transcription factor Rx3, thereby protecting the future telencephalon from acquiring eye identity. This BMP-driven mechanism initiates the establishment of the telencephalon prior to the involvement of Wnt antagonists from the anterior neural border. Furthermore, we demonstrate that Rx3 and BMP are respectively required to maintain and restrict the chemokine receptor cxcr4a, which in turn contributes to the morphogenetic separation of eye-field and telencephalic cells during early neurulation. Copyright © 2012 Elsevier Inc. All rights reserved.

Development of warrants for installation of dual right-turn lanes at signalized intersections.

DOT National Transportation Integrated Search

2012-04-01

Right-turn lanes provide space for the deceleration and storage of right-turn vehicles, and separate turning vehicles : from through movements. Dual right-turn lanes are increasingly used at urban intersections primarily for two : reasons: (1) to acc...

Analysis of cutting force signals by wavelet packet transform for surface roughness monitoring in CNC turning

NASA Astrophysics Data System (ADS)

García Plaza, E.; Núñez López, P. J.

2018-01-01

On-line monitoring of surface finish in machining processes has proven to be a substantial advancement over traditional post-process quality control techniques by reducing inspection times and costs and by avoiding the manufacture of defective products. This study applied techniques for processing cutting force signals based on the wavelet packet transform (WPT) method for the monitoring of surface finish in computer numerical control (CNC) turning operations. The behaviour of 40 mother wavelets was analysed using three techniques: global packet analysis (G-WPT), and the application of two packet reduction criteria: maximum energy (E-WPT) and maximum entropy (SE-WPT). The optimum signal decomposition level (Lj) was determined to eliminate noise and to obtain information correlated to surface finish. The results obtained with the G-WPT method provided an in-depth analysis of cutting force signals, and frequency ranges and signal characteristics were correlated to surface finish with excellent results in the accuracy and reliability of the predictive models. The radial and tangential cutting force components at low frequency provided most of the information for the monitoring of surface finish. The E-WPT and SE-WPT packet reduction criteria substantially reduced signal processing time, but at the expense of discarding packets with relevant information, which impoverished the results. The G-WPT method was observed to be an ideal procedure for processing cutting force signals applied to the real-time monitoring of surface finish, and was estimated to be highly accurate and reliable at a low analytical-computational cost.

Fluorescent probe for turn-on sensing of L-cysteine by ensemble of AuNCs and polymer protected AuNPs.

PubMed

Xu, Xiaozhe; Qiao, Juan; Li, Nan; Qi, Li; Zhang, Shufeng

2015-06-16

A new fluorescent probe based on ensemble of gold nanoclusters (AuNCs) and polymer protected gold nanoparticles (AuNPs) for turn-on sensing of L-cysteine was designed and prepared. The AuNCs were protected by bovine serum albumin and had strong fluorescence. The polymer protected AuNPs were synthesized by a facile in situ strategy at room temperature and could quench the fluorescence of AuNCs due to the Förster resonance energy transfer. Interestingly, it has been observed that the quenched fluorescence of AuNCs was recovered by L-cysteine, which could induce the aggregation of polymer protected AuNPs by sulfur group. Then the prepared fluorescent probe was successfully used for determination of L-Cys in human urines, which would have an evolving aspect and promote the subsequent exploration. Copyright © 2015 Elsevier B.V. All rights reserved.

SLC7 family transporters control the establishment of left-right asymmetry during organogenesis in medaka by activating mTOR signaling.

PubMed

Asaoka, Yoichi; Nagai, Yoko; Namae, Misako; Furutani-Seiki, Makoto; Nishina, Hiroshi

2016-05-20

The precise government of the left-right (LR) specification of an organ is an essential aspect of its morphogenesis. Multiple signaling cascades have been implicated in the establishment of vertebrate LR asymmetry. Recently, mTOR signaling was found to critically regulate the development of LR asymmetry in zebrafish. However, the upstream factor(s) that activate mTOR signaling in the context of LR specification are as yet unknown. In this study, we identify the SLC7 amino acid transporters Slc7a7 and Slc7a8 as novel regulators of LR asymmetry development in the small fish medaka. Knockdown of Slc7a7 and/or Slc7a8 in medaka embryos disrupted LR organ asymmetries. Depletion of Slc7a7 hindered left-sided expression of the southpaw (spaw) gene, which is responsible for LR axis determination. Work at the cellular level revealed that Slc7a7 coordinates ciliogenesis in the epithelium of Kupffer's vesicle and thereby the generation of the nodal fluid flow required for LR asymmetry. Interestingly, knockdown of Slc7a7 depressed mTOR signaling activity in medaka embryos. Treatment with rapamycin, an inhibitor of mTOR signaling, together with Slc7a7 knockdown synergistically perturbed spaw expression, indicating an interaction between Slc7a7 and mTOR signaling affecting gene expression required for LR specification. Taken together, our results demonstrate that Slc7a7 governs the regulation of LR asymmetry development via the activation of mTOR signaling. Copyright © 2016 Elsevier Inc. All rights reserved.

A Wnt5 Activity Asymmetry and Intercellular Signaling via PCP Proteins Polarize Node Cells for Left-Right Symmetry Breaking.

PubMed

Minegishi, Katsura; Hashimoto, Masakazu; Ajima, Rieko; Takaoka, Katsuyoshi; Shinohara, Kyosuke; Ikawa, Yayoi; Nishimura, Hiromi; McMahon, Andrew P; Willert, Karl; Okada, Yasushi; Sasaki, Hiroshi; Shi, Dongbo; Fujimori, Toshihiko; Ohtsuka, Toshihisa; Igarashi, Yasunobu; Yamaguchi, Terry P; Shimono, Akihiko; Shiratori, Hidetaka; Hamada, Hiroshi

2017-03-13

Polarization of node cells along the anterior-posterior axis of mouse embryos is responsible for left-right symmetry breaking. How node cells become polarized has remained unknown, however. Wnt5a and Wnt5b are expressed posteriorly relative to the node, whereas genes for Sfrp inhibitors of Wnt signaling are expressed anteriorly. Here we show that polarization of node cells is impaired in Wnt5a -/- Wnt5b -/- and Sfrp mutant embryos, and also in the presence of a uniform distribution of Wnt5a or Sfrp1, suggesting that Wnt5 and Sfrp proteins act as instructive signals in this process. The absence of planar cell polarity (PCP) core proteins Prickle1 and Prickle2 in individual cells or local forced expression of Wnt5a perturbed polarization of neighboring wild-type cells. Our results suggest that opposing gradients of Wnt5a and Wnt5b and of their Sfrp inhibitors, together with intercellular signaling via PCP proteins, polarize node cells along the anterior-posterior axis for breaking of left-right symmetry. Copyright © 2017 Elsevier Inc. All rights reserved.

Hydrodynamics of Turning Flocks.

PubMed

Yang, Xingbo; Marchetti, M Cristina

2015-12-18

We present a hydrodynamic model of flocking that generalizes the familiar Toner-Tu equations to incorporate turning inertia of well-polarized flocks. The continuum equations controlled by only two dimensionless parameters, orientational inertia and alignment strength, are derived by coarse-graining the inertial spin model recently proposed by Cavagna et al. The interplay between orientational inertia and bend elasticity of the flock yields anisotropic spin waves that mediate the propagation of turning information throughout the flock. The coupling between spin-current density to the local vorticity field through a nonlinear friction gives rise to a hydrodynamic mode with angular-dependent propagation speed at long wavelengths. This mode becomes unstable as a result of the growth of bend and splay deformations augmented by the spin wave, signaling the transition to complex spatiotemporal patterns of continuously turning and swirling flocks.

Brain MRI signal abnormalities and right-to-left shunting in asymptomatic military divers.

PubMed

Gempp, Emmanuel; Sbardella, Fabrice; Stephant, Eric; Constantin, Pascal; De Maistre, Sebastien; Louge, Pierre; Blatteau, Jean-Eric

2010-11-01

We conducted a controlled study to assess the prevalence of brain MRI hyperintense signals and their correlation with right-to-left shunting (RLS) in military divers. We prospectively enrolled 32 asymptomatic military divers under 41 yr of age and 32 non-diving healthy subjects matched with respect to age and vascular disease risk factors. We examined both groups with a 3-Tesla brain MRI; RLS was detected using transcranial pulsed Doppler in divers only. Hyperintense spots were observed in 43.7% of the divers and 21.8% of the control subjects. In particular, divers with significant shunting exhibited a higher prevalence of hyperintensities compared to those with slight or no RLS (75% vs. 25%, respectively). Linear trend analysis also revealed a positive correlation between focal white matter changes, determined using a validated visual rating scale and the RLS grade. Healthy military divers with a hemodynamically relevant RLS have an increased likelihood of cerebral hyperintense spots compared to age-matched normal subjects. The clinical relevance of these MRI signal abnormalities and their causal relationship with diving remain unclear.

Investigation on quench initiation and propagation characteristics of GdBCO coil co-wound with a stainless steel tape as turn-to-turn metallic insulation.

PubMed

Kim, Y G; Song, J B; Choi, Y H; Yang, D G; Kim, S G; Lee, H G

2016-11-01

This paper investigates the quench initiation and propagation characteristics of a metallic insulation (MI) coil by conducting thermal quench tests for a GdBCO single-pancake coil co-wound with a stainless steel tape as the turn-to-turn MI. The test results confirmed that the MI coil exhibited superior thermal and electrical stabilities compared to the conventional coils co-wound with organic insulation material because the operating current could flow along the radial direction due to the existence of a turn-to-turn contact when a local hot spot was generated. The results of the quench test at a heater current (I h ) of 12, 13, and 14 A indicate that the MI coil possesses a self-protecting characteristic resulting from the "current bypass" through the turn-to-turn contact. However, the test coil was not self-protecting at I h = 15 A because the Joule heat energy generated by the radial current flow was not completely dissipated due to the characteristic resistance of the metallic insulation tape and the non-superconducting materials, including the substrate, stabilizer, and buffer layers within the high-temperature superconductor (HTS) tape. Even though the MI coil possesses superior thermal and electrical stability relative to those of conventional HTS coils co-wound with an organic material as turn-to-turn insulation, it is essential to consider the critical role of the Joule heat energy resulting from the operating current and stored magnetic energy as well as the characteristic resistances in order to further develop self-protective 2G HTS magnets.

Toll-like Receptor 4 Signaling Confers Cardiac Protection Against Ischemic Injury via Inducible Nitric Oxide Synthase- and Soluble Guanylate Cyclase-dependent Mechanisms

PubMed Central

Wang, E; Feng, Yan; Zhang, Ming; Zou, Lin; Li, Yan; Buys, Emmanuel S.; Huang, Peigen; Brouckaert, Peter; Chao, Wei

2011-01-01

Background Prior administration of a small dose of lipopolysaccharide confers a cardiac protection against ischemia-reperfusion injury. However, the signaling mechanisms that control the protection are incompletely understood. We tested the hypothesis that TLR4 mediates the ability of lipopolysaccharide to protect against cardiac ischemia-reperfusion injury through distinct intracellular pathways involving myeloid differentiation factor 88 (MyD88), TIR-domain-containing adaptor protein inducing interferon-β–mediated transcription-factor (Trif), inducible nitric-oxide synthase (iNOS), and soluble guanylate cyclase (sGC). Methods Wild-type mice and the genetically modified mice, i.e., TLR4-deficient (TLR4-def), TLR2 knockout (TLR2−/−), MyD88−/−, Trif−/−, iNOS−/−, and sGCα1−/−, were treated with normal saline or 0.1 mg/kg of lipopolysaccharide, intraperitoneally. Twenty-four hours later, isolated hearts were perfused in a Langendorff apparatus and subsequently subjected to 30 min of global ischemia and reperfusion for up to 60 min. Left ventricular function and myocardial infarction sizes were examined. Results Compared to saline-treated mice, lipopolysaccharide-treated mice had markedly improved left ventricular developed pressure and dP/dtmax (P < 0.01) and reduced MI sizes (37.2 ± 3.4% vs. 19.8 ± 4.9%, P < 0.01) after ischemia-reperfusion. The cardiac protective effect of lipopolysaccharide was abolished in the TLR4-def and MyD88−/− mice, but remained intact in TLR2−/− or Trif−/− mice. iNOS−/− mice or wild-type mice treated with the iNOS inhibitor 1400W failed to respond to the TLR4-induced nitric oxide production and were not protected by the lipopolysaccharide preconditioning. While sGC 1−/− mice had robust nitric oxide production in response to lipopolysaccharide, they were not protected by the TLR4-elicited cardiac protection. Conclusions TLR4 activation confers a potent cardiac protection against ischemia

Safety analysis of urban signalized intersections under mixed traffic.

PubMed

S, Anjana; M V L R, Anjaneyulu

2015-02-01

This study examined the crash causative factors of signalized intersections under mixed traffic using advanced statistical models. Hierarchical Poisson regression and logistic regression models were developed to predict the crash frequency and severity of signalized intersection approaches. The prediction models helped to develop general safety countermeasures for signalized intersections. The study shows that exclusive left turn lanes and countdown timers are beneficial for improving the safety of signalized intersections. Safety is also influenced by the presence of a surveillance camera, green time, median width, traffic volume, and proportion of two wheelers in the traffic stream. The factors that influence the severity of crashes were also identified in this study. As a practical application, the safe values of deviation of green time provided from design green time, with varying traffic volume, is presented in this study. This is a useful tool for setting the appropriate green time for a signalized intersection approach with variations in the traffic volume. Copyright © 2014 Elsevier Ltd. All rights reserved.

No Community Left Behind

ERIC Educational Resources Information Center

Schlechty, Phillip C.

2008-01-01

The debate over the reauthorization of No Child Left Behind (NCLB) generally overlooks--or looks past--what may be the most fundamental flaw in that legislation. As the law is now written, decisions regarding what the young should know and be able to do are removed from the hands of parents and local community leaders and turned over to officials…

Training strategies and materials.

DOT National Transportation Integrated Search

2008-08-01

TxDOT project 0-5840 Development of Left-Turn Operations Guidelines at Signalized Intersections has developed : guidelines for recommending the most appropriate left-turn phasing treatments at signalized intersections by investigating all : asp...

Intraciliary calcium oscillations initiate vertebrate left-right asymmetry.

PubMed

Yuan, Shiaulou; Zhao, Lu; Brueckner, Martina; Sun, Zhaoxia

2015-03-02

Bilateral symmetry during vertebrate development is broken at the left-right organizer (LRO) by ciliary motility and the resultant directional flow of extracellular fluid. However, how ciliary motility is perceived and transduced into asymmetrical intracellular signaling at the LRO remains controversial. Previous work has indicated that sensory cilia and polycystin-2 (Pkd2), a cation channel, are required for sensing ciliary motility, yet their function and the molecular mechanism linking both to left-right signaling cascades are unknown. Here we report novel intraciliary calcium oscillations (ICOs) at the LRO that connect ciliary sensation of ciliary motility to downstream left-right signaling. Utilizing cilia-targeted genetically encoded calcium indicators in live zebrafish embryos, we show that ICOs depend on Pkd2 and are left-biased at the LRO in response to ciliary motility. Asymmetric ICOs occur with onset of LRO ciliary motility, thus representing the earliest known LR asymmetric molecular signal. Suppression of ICOs using a cilia-targeted calcium sink reveals that they are essential for LR development. These findings demonstrate that intraciliary calcium initiates LR development and identify cilia as a functional ion signaling compartment connecting ciliary motility and flow to molecular LR signaling. Copyright © 2015 Elsevier Ltd. All rights reserved.

Identification of signaling pathways associated with cancer protection in Laron syndrome.

PubMed

Lapkina-Gendler, Lena; Rotem, Itai; Pasmanik-Chor, Metsada; Gurwitz, David; Sarfstein, Rive; Laron, Zvi; Werner, Haim

2016-05-01

The growth hormone (GH)-insulin-like growth factor-1 (IGF1) pathway emerged in recent years as a critical player in cancer biology. Enhanced expression or activation of specific components of the GH-IGF1 axis, including the IGF1 receptor (IGF1R), is consistently associated with a transformed phenotype. Recent epidemiological studies have shown that patients with Laron syndrome (LS), the best-characterized entity among the congenital IGF1 deficiencies, seem to be protected from cancer development. To identify IGF1-dependent genes and signaling pathways associated with cancer protection in LS, we conducted a genome-wide analysis using immortalized lymphoblastoid cells derived from LS patients and healthy controls of the same gender, age range, and ethnic origin. Our analyses identified a collection of genes that are either over- or under-represented in LS-derived lymphoblastoids. Gene differential expression occurs in several gene families, including cell cycle, metabolic control, cytokine-cytokine receptor interaction, Jak-STAT signaling, and PI3K-AKT signaling. Major differences between LS and healthy controls were also noticed in pathways associated with cell cycle distribution, apoptosis, and autophagy. Our results highlight the key role of the GH-IGF1 axis in the initiation and progression of cancer. Furthermore, data are consistent with the concept that homozygous congenital IGF1 deficiency may confer protection against future tumor development. © 2016 Society for Endocrinology.

Cilia in vertebrate left-right patterning.

PubMed

Dasgupta, Agnik; Amack, Jeffrey D

2016-12-19

Understanding how left-right (LR) asymmetry is generated in vertebrate embryos is an important problem in developmental biology. In humans, a failure to align the left and right sides of cardiovascular and/or gastrointestinal systems often results in birth defects. Evidence from patients and animal models has implicated cilia in the process of left-right patterning. Here, we review the proposed functions for cilia in establishing LR asymmetry, which include creating transient leftward fluid flows in an embryonic 'left-right organizer'. These flows direct asymmetric activation of a conserved Nodal (TGFβ) signalling pathway that guides asymmetric morphogenesis of developing organs. We discuss the leading hypotheses for how cilia-generated asymmetric fluid flows are translated into asymmetric molecular signals. We also discuss emerging mechanisms that control the subcellular positioning of cilia and the cellular architecture of the left-right organizer, both of which are critical for effective cilia function during left-right patterning. Finally, using mosaic cell-labelling and time-lapse imaging in the zebrafish embryo, we provide new evidence that precursor cells maintain their relative positions as they give rise to the ciliated left-right organizer. This suggests the possibility that these cells acquire left-right positional information prior to the appearance of cilia.This article is part of the themed issue 'Provocative questions in left-right asymmetry'. © 2016 The Author(s).

Continuous light and L-NAME-induced left ventricular remodelling: different protection with melatonin and captopril.

PubMed

Simko, Fedor; Pechanova, Olga; Pelouch, Vaclav; Krajcirovicova, Kristina; Celec, Peter; Palffy, Roland; Bednarova, Kristina; Vrankova, Stanislava; Adamcova, Michaela; Paulis, Ludovit

2010-09-01

Blood pressure enhancement induced by continuous light exposure represents an attractive but rarely investigated model of experimental hypertension. The aim of this study was to show whether the combination of continuous light (24 h/day) exposure and chronic N-nitro-L-arginine-methyl ester (L-NAME) treatment induces remodelling of the left ventricle and whether captopril or melatonin can modify these potential alterations. Six groups of 3-month-old Wistar rats (nine per group) were treated for 6 weeks: control (untreated), L-NAME (40 mg/kg per day), exposed to continuous light, L-NAME treated and exposed to continuous light (L24), L24 rats treated with either captopril 100 mg/kg per day, or melatonin (10 mg/kg/24 h). Systolic blood pressure (SBP), relative weights of the left ventricle, endothelial nitric oxide synthase (eNOS) and angiotensin-converting enzyme (ACE) expression in tissues, malondialdehyde and advanced oxidation protein product concentrations in the plasma and hydroxyproline levels in collagenous protein fractions were measured. The continuous light and L-NAME treatment led to hypertension, left ventricular hypertrophy (LVH) and fibrosis. An increase in SBP was completely prevented by captopril and partly by melatonin in the L24 group. Both drugs reduced oxidative damage and attenuated enhanced expression of ACE in the myocardium. Neither of the drugs prevented the attenuation of eNOS expression in the combined hypertensive model. Only captopril reduced LVH development in L24, whereas captopril and melatonin reduced left ventricular hydroxyproline concentrations in soluble and insoluble collagen, respectively. The total hydroxyproline concentration was reduced only by melatonin. In hypertension induced by a combination of continuous light and L-NAME treatment, melatonin and captopril protect the heart against pathological left ventricular remodelling differently.

Protection from obesity and diabetes by blockade of TGF-β/Smad3 signaling

PubMed Central

Yadav, Hariom; Quijano, Celia; Kamaraju, Anil K.; Gavrilova, Oksana; Malek, Rana; Chen, Weiping; Zerfas, Patricia; Zhigang, Duan; Wright, Elizabeth C.; Stuelten, Christina; Sun, Peter; Lonning, Scott; Skarulis, Monica; Sumner, Anne E.; Finkel, Toren; Rane, Sushil G.

2011-01-01

SUMMARY Imbalances in glucose and energy homeostasis are at the core of the worldwide epidemic of obesity and diabetes. Here, we illustrate an important role of the TGF-β/Smad3 signaling pathway in regulating glucose and energy homeostasis. Smad3 deficient mice are protected from diet-induced obesity and diabetes. Interestingly, the metabolic protection is accompanied by Smad3−/− white adipose tissue acquiring the bioenergetic and gene expression profile of brown fat/skeletal muscle. Smad3−/− adipocytes demonstrate a marked increase in mitochondrial biogenesis, with a corresponding increase in basal respiration, and Smad3 acts as a repressor of PGC-1α expression. We observe significant correlation between TGF-β1 levels and adiposity in rodents and humans. Further, systemic blockade of TGF-β1 signaling protects mice from obesity, diabetes and hepatic steatosis. Together, these results demonstrate that TGF-β signaling regulates glucose tolerance and energy homeostasis and suggest that modulation of TGF-β1 activity might be an effective treatment strategy for obesity and diabetes. PMID:21723505

An extended car-following model at un-signalized intersections under V2V communication environment

PubMed Central

Wang, Tao; Li, Peng

2018-01-01

An extended car-following model is proposed in this paper to analyze the impacts of V2V (vehicle to vehicle) communication on the micro driving behavior at the un-signalized intersection. A four-leg un-signalized intersection with twelve streams (left-turn, through movement, and right turn from each leg) is used. The effect of the guidance strategy on the reduction of the rate of stops and total delay is explored by comparing the proposed model and the traditional FVD car-following model. The numerical results illustrate that potential conflicts between vehicles can be predicted and some stops can be avoided by decelerating in advance. The driving comfort and traffic efficiency can be improved accordingly. More benefits could be obtained under the long communication range, low to medium traffic density, and simple traffic pattern conditions. PMID:29425243

Snail/beta-catenin signaling protects breast cancer cells from hypoxia attack

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

Scherbakov, Alexander M., E-mail: alex.scherbakov@gmail.com; Stefanova, Lidia B.; Sorokin, Danila V.

2013-12-10

The tolerance of cancer cells to hypoxia depends on the combination of different factors – from increase of glycolysis (Warburg Effect) to activation of intracellular growth/apoptotic pathways. Less is known about the influence of epithelial–mesenchymal transition (EMT) and EMT-associated pathways on the cell sensitivity to hypoxia. The aim of this study was to explore the role of Snail signaling, one of the key EMT pathways, in the mediating of hypoxia response and regulation of cell sensitivity to hypoxia, using as a model in vitro cultured breast cancer cells. Earlier we have shown that estrogen-independent HBL-100 breast cancer cells differ frommore » estrogen-dependent MCF-7 cells with increased expression of Snail1, and demonstrated Snail1 involvement into formation of hormone-resistant phenotype. Because Snail1 belongs to hypoxia-activated proteins, here we studied the influence of Snail1 signaling on the cell tolerance to hypoxia. We found that Snail1-enriched HBL-100 cells were less sensitive to hypoxia-induced growth suppression if compared with MCF-7 line (31% MCF-7 vs. 71% HBL-100 cell viability after 1% O{sub 2} atmosphere for 3 days). Snail1 knock-down enhanced the hypoxia-induced inhibition of cell proliferation giving the direct evidence of Snail1 involvement into cell protection from hypoxia attack. The protective effect of Snail1 was shown to be mediated, at least in a part, via beta-catenin which positively regulated expression of HIF-1-dependent genes. Finally, we found that cell tolerance to hypoxia was accompanied with the failure in the phosphorylation of AMPK – the key energy sensor, and demonstrated an inverse relationship between AMPK and Snail/beta-catenin signaling. Totally, our data show that Snail1 and beta-catenin, besides association with loss of hormone dependence, protect cancer cells from hypoxia and may serve as an important target in the treatment of breast cancer. Moreover, we suggest that the level of these proteins as

Expanded turn conformations: characterization and sequence-structure correspondence in alpha-turns with implications in helix folding.

PubMed

Dasgupta, Bhaskar; Pal, Lipika; Basu, Gautam; Chakrabarti, Pinak

2004-05-01

Like the beta-turns, which are characterized by a limiting distance between residues two positions apart (i, i+3), a distance criterion (involving residues at positions i and i+4) is used here to identify alpha-turns from a database of known protein structures. At least 15 classes of alpha-turns have been enumerated based on the location in the phi,psi space of the three central residues (i+1 to i+3)-one of the major being the class AAA, where the residues occupy the conventional helical backbone torsion angles. However, moving towards the C-terminal end of the turn, there is a shift in the phi,psi angles towards more negative phi, such that the electrostatic repulsion between two consecutive carbonyl oxygen atoms is reduced. Except for the last position (i+4), there is not much similarity in residue composition at different positions of hydrogen and non-hydrogen bonded AAA turns. The presence or absence of Pro at i+1 position of alpha- and beta-turns has a bearing on whether the turn is hydrogen-bonded or without a hydrogen bond. In the tertiary structure, alpha-turns are more likely to be found in beta-hairpin loops. The residue composition at the beginning of the hydrogen bonded AAA alpha-turn has similarity with type I beta-turn and N-terminal positions of helices, but the last position matches with the C-terminal capping position of helices, suggesting that the existence of a "helix cap signal" at i+4 position prevents alpha-turns from growing into helices. Our results also provide new insights into alpha-helix nucleation and folding. Copyright 2004 Wiley-Liss, Inc.

Integration of nodal and BMP signals in the heart requires FoxH1 to create left-right differences in cell migration rates that direct cardiac asymmetry.

PubMed

Lenhart, Kari F; Holtzman, Nathalia G; Williams, Jessica R; Burdine, Rebecca D

2013-01-01

Failure to properly establish the left-right (L/R) axis is a major cause of congenital heart defects in humans, but how L/R patterning of the embryo leads to asymmetric cardiac morphogenesis is still unclear. We find that asymmetric Nodal signaling on the left and Bmp signaling act in parallel to establish zebrafish cardiac laterality by modulating cell migration velocities across the L/R axis. Moreover, we demonstrate that Nodal plays the crucial role in generating asymmetry in the heart and that Bmp signaling via Bmp4 is dispensable in the presence of asymmetric Nodal signaling. In addition, we identify a previously unappreciated role for the Nodal-transcription factor FoxH1 in mediating cell responsiveness to Bmp, further linking the control of these two pathways in the heart. The interplay between these TGFβ pathways is complex, with Nodal signaling potentially acting to limit the response to Bmp pathway activation and the dosage of Bmp signals being critical to limit migration rates. These findings have implications for understanding the complex genetic interactions that lead to congenital heart disease in humans.

[Establishment of visceral left-right asymmetry in mammals: the role of ciliary action and leftward fluid flow in the region of Hensen's node].

PubMed

Ermakov, A S

2013-01-01

During individual development of vertebrates, the anteroposterior, dorsoventral, and left-right axes of the body are established. Although the vertebrates are bilaterally symmetric outside, their internal structure is asymmetric. Of special interest is the insight into establishment of visceral left-right asymmetry in mammals, since it has not only basic but also an applied medical significance. As early as 1976, it was hypothesized that the ciliary action could be associated with the establishment of left-right asymmetry in mammals. Currently, the majority of researchers agree that the ciliary action in the region of Hensen's node and the resulting leftward laminar fluid flow play a key role in the loss of bilateral symmetry and triggering of expression of the genes constituting the Nodal-Ptx2 signaling cascade, specific of the left side of the embryo. The particular mechanism underlying this phenomenon is still insufficiently clear. There are three competing standpoints on how leftward fluid flow induces expression of several genes in the left side of the embryo. The morphogen gradient hypothesis postulates that the leftward flow creates a high concentration of a signaling biomolecule in the left side of Hensen's node, which, in turn, stimulates triggering of.gene expression of the Nodal-Ptx2 cascade. The biomechanical hypothesis (or two-cilia model) states that the immotile cilia located in the periphery of Hensen's node act as mechanosensors, activate mechanosensory ion channels, and trigger calcium signaling in the left side of the embryo. Finally, the "shuttle-bus model" holds that leftward fluid flow carries the lipid vesicles, which are crashed when colliding immotile cilia in the periphery of Hensen's node to release the contained signaling biomolecules. It is also noteworthy that the association between the ciliary action and establishment of asymmetry has been recently discovered in representatives of the lower invertebrates. In this paper, the author

Development and preliminary testing of an automatic turning movements identification system : final report, February 2010.

DOT National Transportation Integrated Search

2010-02-01

It is important for many applications, such as intersection delay estimation and adaptive signal : control, to obtain vehicle turning movement information at signalized intersections. However, : vehicle turning movement information is very time consu...

Infarct-remodeled myocardium is receptive to protection by isoflurane postconditioning: role of protein kinase B/Akt signaling.

PubMed

Feng, Jianhua; Fischer, Gregor; Lucchinetti, Eliana; Zhu, Min; Bestmann, Lukas; Jegger, David; Arras, Margarete; Pasch, Thomas; Perriard, Jean-Claude; Schaub, Marcus C; Zaugg, Michael

2006-05-01

Postinfarct remodeled myocardium exhibits numerous structural and biochemical alterations. So far, it is unknown whether postconditioning elicited by volatile anesthetics can also provide protection in the remodeled myocardium. Myocardial infarct was induced in male Wistar rats by ligation of the left anterior descending coronary artery. Six weeks later, hearts were buffer-perfused and exposed to 40 min of ischemia followed by 90 min of reperfusion. Anesthetic postconditioning was induced by 15 min of 2.1 vol% isoflurane. In some experiments, LY294002 (15 microM), a phosphatidylinositol 3-kinase inhibitor, was coadministered with isoflurane. Masson's trichrome staining, immunohistochemistry, Western blot analysis, and reverse-transcription polymerase chain reaction served to confirm remodeling. In buffer-perfused hearts, functional recovery was recorded, and acute infarct size was measured using 1% triphenyltetrazolium chloride staining and lactate dehydrogenase release during reperfusion. Western blot analysis was used to determine phosphorylation of reperfusion injury salvage kinases including protein kinase B/Akt and its downstream targets after 15 min of reperfusion. Infarct hearts exhibited typical macroscopic and molecular changes of remodeling. Isoflurane postconditioning improved functional recovery and decreased acute infarct size, as determined by triphenyltetrazolium (35 +/- 5% in unprotected hearts vs. 8 +/- 3% in anesthetic postconditioning; P < 0.05) and lactate dehydrogenase release. This protection was abolished by LY294002, which inhibited phosphorylation of protein kinase B/Akt and its downstream targets glycogen synthase kinase 3beta, endothelial nitric oxide synthase, and p70S6 kinase. Infarct-remodeled myocardium is receptive to protection by isoflurane postconditioning via protein kinase B/Akt signaling. This is the first time to demonstrate that anesthetic postconditioning retains its marked protection in diseased myocardium.

49 CFR 1242.58 - Operating signals and interlockers, operating drawbridges, highway crossing protection (accounts...

Code of Federal Regulations, 2014 CFR

2014-10-01

... drawbridges, highway crossing protection (accounts XX-51-59, XX-51-60 and XX-51-61). 1242.58 Section 1242.58... Operating signals and interlockers, operating drawbridges, highway crossing protection (accounts XX-51-59..., interlockers, drawbridges and highway crossings are located. ...

49 CFR 1242.58 - Operating signals and interlockers, operating drawbridges, highway crossing protection (accounts...

Code of Federal Regulations, 2011 CFR

2011-10-01

... drawbridges, highway crossing protection (accounts XX-51-59, XX-51-60 and XX-51-61). 1242.58 Section 1242.58... Operating signals and interlockers, operating drawbridges, highway crossing protection (accounts XX-51-59..., interlockers, drawbridges and highway crossings are located. ...

49 CFR 1242.58 - Operating signals and interlockers, operating drawbridges, highway crossing protection (accounts...

Code of Federal Regulations, 2012 CFR

2012-10-01

... drawbridges, highway crossing protection (accounts XX-51-59, XX-51-60 and XX-51-61). 1242.58 Section 1242.58... Operating signals and interlockers, operating drawbridges, highway crossing protection (accounts XX-51-59..., interlockers, drawbridges and highway crossings are located. ...

49 CFR 1242.58 - Operating signals and interlockers, operating drawbridges, highway crossing protection (accounts...

Code of Federal Regulations, 2013 CFR

2013-10-01

... drawbridges, highway crossing protection (accounts XX-51-59, XX-51-60 and XX-51-61). 1242.58 Section 1242.58... Operating signals and interlockers, operating drawbridges, highway crossing protection (accounts XX-51-59..., interlockers, drawbridges and highway crossings are located. ...

Right-Turn Traffic Volume Adjustments in Traffic Signal Warrant Analysis

DOT National Transportation Integrated Search

2015-01-01

To accomplish this research, a comprehensive literature review of existing guidelines and findings based on national and local studies was conducted. Ultimately, guidelines for consistent application for adjusting right-turn traffic volumes were deve...

Assessment of Device-Related Thrombus and Associated Clinical Outcomes With the WATCHMAN Left Atrial Appendage Closure Device for Embolic Protection in Patients With Atrial Fibrillation (from the PROTECT-AF Trial).

PubMed

Main, Michael L; Fan, Dali; Reddy, Vivek Y; Holmes, David R; Gordon, Nicole T; Coggins, Tina R; House, John A; Liao, Lawrence; Rabineau, Dawn; Latus, George G; Huber, Kenneth C; Sievert, Horst; Wright, Richard F; Doshi, Shephal K; Douglas, Pamela S

2016-04-01

Left atrial appendage closure with the WATCHMAN device is an alternative to anticoagulation for stroke prevention in selected patients with atrial fibrillation (AF). LA device-related thrombus (DRT) is poorly defined and understood. We aimed to (1) develop consensus echocardiographic diagnostic criteria for DRT; (2) estimate the incidence of DRT; and (3) determine clinical event rates in patients with DRT. In phase 1 (training), a training manual was developed and reviewed by 3 echocardiographers with left atrial appendage closure device experience. All available transesophageal (TEE) studies in the WATCHMAN left atrial appendage system for embolic protection in patients with atrial fibrillation (PROTECT-AF) trial patients with suspected DRT were reviewed in 2 subsequent phases. In phase 2 (primary blind read), each reviewer independently scored each study for DRT, and final echo criteria were developed. Unanimously scored studies were considered adjudicated, whereas all others were reevaluated by all reviewers in phase 3 (group adjudication read). DRT was suspected in 35 of 485 patients by the site investigator, the echocardiography core laboratory, or both; 93 of the individual TEE studies were available for review. In phase 2, 3 readers agreed on 67 (72%) of time points. Based on phases 1 and 2, 5 DRT criteria were developed. In phase 3, studies without agreement in phase 2 were adjudicated using these criteria. Overall, at least 1 TEE was DRT positive in 27 (5.7%) PROTECT-AF patients. Stroke, peripheral embolism, or cardiac/unexplained death occurred in subjects with DRT at a rate of 3.4 per 100 patient-years follow-up. In conclusion, DRT were identified on at least 1 TEE in 27 PROTECT-AF patients, indicating a DRT incidence of 5.7%. Primary efficacy events in patients with DRT occurred at a rate of 3.4 per 100 patient-years follow-up, intermediate in frequency between event rates previously reported for the overall device and warfarin arms in PROTECT

Characterization of beta-turn and Asx-turns mimicry in a model peptide: stabilization via C--H . . . O interaction.

PubMed

Thakur, A K; Kishore, R

2006-04-15

The chemical synthesis and single-crystal X-ray diffraction analysis of a model peptide, Boc-Thr-Thr-NH2 (1) comprised of proteinogenic residues bearing an amphiphilic Cbeta -stereogenic center, has been described. Interestingly, the analysis of its molecular structure revealed the existence of a distinct conformation that mimics a typical beta-turn and Asx-turns, i.e., the two Thr residues occupy the left- and right-corner positions. The main-chain torsion angles of the N- and C-terminal residues i.e., semiextended: phi = -68.9 degrees , psi = 128.6 degrees ; semifolded: phi = -138.1 degrees , psi = 2.5 degrees conformations, respectively, in conjunction with a gauche- disposition of the obligatory C-terminus Thr CgammaH3 group, characterize the occurrence of the newly described beta-turn- and Asx-turns-like topology. The preferred molecular structure is suggested to be stabilized by an effective nonconventional main-chain to side-chain Ci=O . . . H--Cgamma(i+2)-type intraturn hydrogen bond. Noteworthy, the observed topology of the resulting 10-membered hydrogen-bonded ring is essentially similar to the one perceived for a classical beta-turn and the Asx-turns, stabilized by a conventional intraturn hydrogen bond. Considering the signs as well as magnitudes of the backbone torsion angles and the orientation of the central peptide bond, the overall mimicked topology resembles the type II beta-turn or type II Asx-turns. An analysis of Xaa-Thr sequences in high-resolution X-ray elucidated protein structures revealed the novel topology prevalence in functional proteins (unpublished). In view of indubitable structural as well as functional importance of nonconventional interactions in bioorganic and biomacromolecules, we intend to highlight the participation of Thr CgammaH in the creation of a short-range C=O . . . H--Cgamma -type interaction in peptides and proteins. Copyright 2006 Wiley Periodicals, Inc.

S-Nitrosylation: NO-Related Redox Signaling to Protect Against Oxidative Stress

PubMed Central

STEENBERGEN, CHARLES; MURPHY, ELIZABETH

2007-01-01

Nitric oxide (NO) plays an important role in the regulation of cardiovascular function. S-nitrosylation, the covalent attachment of an NO moiety to sulfhydryl residues of proteins, resulting in the formation of S-nitrosothiols (SNOs), is a prevalent posttranslational protein modification involved in redox-based cellular signaling. Under physiologic conditions, protein S>-nitrosylation and SNOs provide protection preventing further cellular oxidative and nitrosative stress. However, oxidative stress and the resultant dysfunction of NO signaling have been implicated in the pathogenesis of cardiovascular diseases. PMID:16987022

How the Wnt signaling pathway protects from neurodegeneration: the mitochondrial scenario

PubMed Central

Arrázola, Macarena S.; Silva-Alvarez, Carmen; Inestrosa, Nibaldo C.

2015-01-01

Alzheimer’s disease (AD) is the most common neurodegenerative disorder and is characterized by progressive memory loss and cognitive decline. One of the hallmarks of AD is the overproduction of amyloid-beta aggregates that range from the toxic soluble oligomer (Aβo) form to extracellular accumulations in the brain. Growing evidence indicates that mitochondrial dysfunction is a common feature of neurodegenerative diseases and is observed at an early stage in the pathogenesis of AD. Reports indicate that mitochondrial structure and function are affected by Aβo and can trigger neuronal cell death. Mitochondria are highly dynamic organelles, and the balance between their fusion and fission processes is essential for neuronal function. Interestingly, in AD, the process known as “mitochondrial dynamics” is also impaired by Aβo. On the other hand, the activation of the Wnt signaling pathway has an essential role in synaptic maintenance and neuronal functions, and its deregulation has also been implicated in AD. We have demonstrated that canonical Wnt signaling, through the Wnt3a ligand, prevents the permeabilization of mitochondrial membranes through the inhibition of the mitochondrial permeability transition pore (mPTP), induced by Aβo. In addition, we showed that non-canonical Wnt signaling, through the Wnt5a ligand, protects mitochondria from fission-fusion alterations in AD. These results suggest new approaches by which different Wnt signaling pathways protect neurons in AD, and support the idea that mitochondria have become potential therapeutic targets for the treatment of neurodegenerative disorders. Here we discuss the neuroprotective role of the canonical and non-canonical Wnt signaling pathways in AD and their differential modulation of mitochondrial processes, associated with mitochondrial dysfunction and neurodegeneration. PMID:25999816

Temporal requirements of insulin/IGF-1 signaling for proteotoxicity protection.

PubMed

Cohen, Ehud; Du, Deguo; Joyce, Derek; Kapernick, Erik A; Volovik, Yuli; Kelly, Jeffery W; Dillin, Andrew

2010-04-01

Toxic protein aggregation (proteotoxicity) is a unifying feature in the development of late-onset human neurodegenerative disorders. Reduction of insulin/IGF-1 signaling (IIS), a prominent lifespan, developmental and reproductive regulatory pathway, protects worms from proteotoxicity associated with the aggregation of the Alzheimer's disease-linked Abeta peptide. We utilized transgenic nematodes that express human Abeta and found that late life IIS reduction efficiently protects from Abeta toxicity without affecting development, reproduction or lifespan. To alleviate proteotoxic stress in the animal, the IIS requires heat shock factor (HSF)-1 to modulate a protein disaggregase, while DAF-16 regulates a presumptive active aggregase, raising the question of how these opposing activities could be co-regulated. One possibility is that HSF-1 and DAF-16 have distinct temporal requirements for protection from proteotoxicity. Using a conditional RNAi approach, we found an early requirement for HSF-1 that is distinct from the adult functions of DAF-16 for protection from proteotoxicity. Our data also indicate that late life IIS reduction can protect from proteotoxicity when it can no longer promote longevity, strengthening the prospect that IIS reduction might be a promising strategy for the treatment of neurodegenerative disorders caused by proteotoxicity.

Identifying protein β-turns with vibrational Raman optical activity.

PubMed

Weymuth, Thomas; Jacob, Christoph R; Reiher, Markus

2011-04-18

β-turns belong to the most important secondary structure elements in proteins. On the basis of density functional calculations, vibrational Raman optical activity signatures of different types of β-turns are established and compared as well as related to other signatures proposed in the literature earlier. Our findings indicate that there are much more characteristic ROA signals of β-turns than have been hitherto suggested. These suggested signatures are, however, found to be valid for the most important type of β-turns. Moreover, we compare the influence of different amino acid side chains on these signatures and investigate the discrimination of β-turns from other secondary structure elements, namely α- and 3(10)-helices. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Eye and head motion during head turns in spaceflight

NASA Technical Reports Server (NTRS)

Thornton, William E.; Uri, John J.; Moore, Thomas P.; Pool, Sam L.

1988-01-01

Eye-head motion was studied pre-, in- and postflight during single voluntary head turns. A transient increase in vestibulo-ocular reflex (VOR) gain occurred early in the flight, but later trended toward normal. This increased gain was produced by a relative increase in eye counterrotation velocity. Asymmetries in gain with right and left turns also occurred, caused by asymmetries in eye counterrotation velocities. These findings were remarkably similar to those from Soviet primate studies using gaze fixation targets, except the human study trended more rapidly toward normal. These findings differ substantially from those measuring VOR gain by head oscillation, in which no significant changes were found inflight. No visual disturbances were noted in either test condition or in normal activities. These head turn studies are the only ones to date documenting any functional change in VOR in weightlessness.

32 CFR 935.134 - Arm signals.

Code of Federal Regulations, 2011 CFR

2011-07-01

... making a turn or coming to a stop shall signal the turn or stop in accordance with this section. (b) A... downward. (c) A signal light or other device may be used in place of an arm signal prescribed in paragraph...

32 CFR 935.134 - Arm signals.

Code of Federal Regulations, 2010 CFR

2010-07-01

... making a turn or coming to a stop shall signal the turn or stop in accordance with this section. (b) A... downward. (c) A signal light or other device may be used in place of an arm signal prescribed in paragraph...

Hydrogen-bonded turns in proteins: The case for a recount

PubMed Central

Panasik, Nick; Fleming, Patrick J.; Rose, George D.

2005-01-01

β-Turns are sites at which proteins change their overall chain direction, and they occur with high frequency in globular proteins. The Protein Data Bank has many instances of conformations that resemble β-turns but lack the characteristic N–H(i) → O=C(i − 3) hydrogen bond of an authentic β-turn. Here, we identify potential hydrogen-bonded β-turns in the coil library, a Web-accessible database utility comprised of all residues not in repetitive secondary structure, neither α-helix nor β-sheet (http://www.roselab.jhu.edu/coil). In particular, candidate turns were identified as four-residue segments satisfying highly relaxed geometric criteria but lacking a strictly defined hydrogen bond. Such candidates were then subjected to a minimization protocol to determine whether slight changes in torsion angles are sufficient to shift the conformation into reference-quality geometry without deviating significantly from the original structure. This approach of applying constrained minimization to known structures reveals a substantial population of previously unidentified, stringently defined, hydrogen-bonded β-turns. In particular, 33% of coil library residues were classified as β-turns prior to minimization. After minimization, 45% of such residues could be classified as β-turns, with another 8% in 310 helixes (which closely resemble type III β-turns). Of the remaining coil library residues, 37% have backbone dihedral angles in left-handed polyproline II structure. PMID:16251367

Hydrogen-bonded turns in proteins: the case for a recount.

PubMed

Panasik, Nick; Fleming, Patrick J; Rose, George D

2005-11-01

Beta-turns are sites at which proteins change their overall chain direction, and they occur with high frequency in globular proteins. The Protein Data Bank has many instances of conformations that resemble beta-turns but lack the characteristic N-H(i) --> O=C(i - 3) hydrogen bond of an authentic beta-turn. Here, we identify potential hydrogen-bonded beta-turns in the coil library, a Web-accessible database utility comprised of all residues not in repetitive secondary structure, neither alpha-helix nor beta-sheet (http://www.roselab.jhu.edu/coil). In particular, candidate turns were identified as four-residue segments satisfying highly relaxed geometric criteria but lacking a strictly defined hydrogen bond. Such candidates were then subjected to a minimization protocol to determine whether slight changes in torsion angles are sufficient to shift the conformation into reference-quality geometry without deviating significantly from the original structure. This approach of applying constrained minimization to known structures reveals a substantial population of previously unidentified, stringently defined, hydrogen-bonded beta-turns. In particular, 33% of coil library residues were classified as beta-turns prior to minimization. After minimization, 45% of such residues could be classified as beta-turns, with another 8% in 3(10) helixes (which closely resemble type III beta-turns). Of the remaining coil library residues, 37% have backbone dihedral angles in left-handed polyproline II structure.

Autotaxin/Lpar3 signaling regulates Kupffer's vesicle formation and left-right asymmetry in zebrafish.

PubMed

Lai, Shih-Lei; Yao, Wan-Ling; Tsao, Ku-Chi; Houben, Anna J S; Albers, Harald M H G; Ovaa, Huib; Moolenaar, Wouter H; Lee, Shyh-Jye

2012-12-01

Left-right (L-R) patterning is essential for proper organ morphogenesis and function. Calcium fluxes in dorsal forerunner cells (DFCs) are known to regulate the formation of Kupffer's vesicle (KV), a central organ for establishing L-R asymmetry in zebrafish. Here, we identify the lipid mediator lysophosphatidic acid (LPA) as a regulator of L-R asymmetry in zebrafish embryos. LPA is produced by Autotaxin (Atx), a secreted lysophospholipase D, and triggers various cellular responses through activation of specific G protein-coupled receptors (Lpar1-6). Knockdown of Atx or LPA receptor 3 (Lpar3) by morpholino oligonucleotides perturbed asymmetric gene expression in lateral plate mesoderm and disrupted organ L-R asymmetries, whereas overexpression of lpar3 partially rescued those defects in both atx and lpar3 morphants. Similar defects were observed in embryos treated with the Atx inhibitor HA130 and the Lpar1-3 inhibitor Ki16425. Knockdown of either Atx or Lpar3 impaired calcium fluxes in DFCs during mid-epiboly stage and compromised DFC cohesive migration, KV formation and ciliogenesis. Application of LPA to DFCs rescued the calcium signal and laterality defects in atx morphants. This LPA-dependent L-R asymmetry is mediated via Wnt signaling, as shown by the accumulation of β-catenin in nuclei at the dorsal side of both atx and lpar3 morphants. Our results suggest a major role for the Atx/Lpar3 signaling axis in regulating KV formation, ciliogenesis and L-R asymmetry via a Wnt-dependent pathway.

STS-92 Mission Specialist Wakata completes his turn driving the M-113

NASA Technical Reports Server (NTRS)

2000-01-01

STS-92 Mission Specialist Koichi Wakata of Japan signals a successful driving lesson on the M-113 he is in. Capt. George Hoggard, trainer with the KSC Fire Department, sits on top. Behind Wakata are Commander Brian Duffy (left) and Leroy Chiao (right), waiting their turns. The practice drive is part of emergency egress training during Terminal Countdown Demonstration Test (TCDT) activities. The tracked vehicle could be used by the crew in the event of an emergency at the pad during which the crew must make a quick exit from the area. The TCDT also provides simulated countdown exercises and opportunities to inspect the mission payloads in the orbiter's payload bay. STS-92 is scheduled to launch Oct. 5 at 9:30 p.m. EDT on the fifth flight to the International Space Station. It will carry two elements of the Space Station, the Integrated Truss Structure Z1 and the third Pressurized Mating Adapter. The mission is also the 100th flight in the Shuttle program.

Left-right asymmetry: cilia and calcium revisited.

PubMed

Blum, Martin; Vick, Philipp

2015-03-02

Leftward flow generated by motile cilia is known to underlie left-right asymmetry in vertebrate embryos. A new study now links intraciliary calcium oscillations to cilia motility and the downstream nodal signaling cascade that drives left-sided development. Copyright © 2015 Elsevier Ltd. All rights reserved.

A case of left inferior vena cava.

PubMed

Yano, R; Hayakawa, D; Emura, S; Chen, H; Ozawa, Y; Taguchi, H; Shoumura, S

2001-12-01

A case of left inferior vena cava (IVC) was found in a 72-year-old male cadaver during student dissection practice in 1999 at Gifu University School of Medicine. It was formed by junction of the left and right common iliac veins at the lower left corner of the 5th lumbar vertebra. This IVC (15-mm caliber) ascended 82 mm along the left side of the abdominal aorta dorsally to the ureter. Receiving the left renal vein, it became 21 mm in caliber and ran obliquely upward for 43 mm across the abdominal aorta. As soon as it received two right renal veins at the level of the 2nd lumbar vertebra, the IVC (25-mm caliber) turned directly above. The present case belongs to Type C of the classification of McClure and Butler (1925), which is based on the combinations of the left and right IVCs, and on their location relative to the ureters. The present case also belongs to Type 1 of the classification of Yoshida et al. (1981). We consider that left IVC in the present case is mainly caused by disappearance of the right supracardinal vein and persistence of the left one during the embryological development of the IVC.

49 CFR 1242.58 - Operating signals and interlockers, operating drawbridges, highway crossing protection (accounts...

Code of Federal Regulations, 2010 CFR

2010-10-01

... drawbridges, highway crossing protection (accounts XX-51-59, XX-51-60 and XX-51-61). 1242.58 Section 1242.58... Operating signals and interlockers, operating drawbridges, highway crossing protection (accounts XX-51-59, XX-51-60 and XX-51-61). Separate common expenses on the basis of total train hours (including train...

Opportunities and limitations for intersection collision intervention-A study of real world 'left turn across path' accidents.

PubMed

Sander, Ulrich

2017-02-01

Turning across the path of oncoming vehicle accidents are frequent and dangerous. To date not many car manufacturers have introduced Automated Emergency Braking (AEB) systems addressing this type of conflict situation, but it is foreseeable that these scenarios will be part of the Euro NCAP 2020 rating. Nine out of ten collisions are caused by the driver of the turning vehicle. An AEB system evaluating the ego and conflict vehicle driver's possibilities to avoid a pending crash by either braking or steering was specified for application in various constellations of vehicle collisions. In virtual simulation, AEB system parameters were varied, covering parameters that are relevant for driver comfort such as longitudinal and lateral acceleration (to define avoidance possibilities), expected steering maneuvers to avoid conflict, and intervention response characteristics (brake delay and ramp up) to assess the safety benefit. The reference simulation showed a potential of the AEB system in the turning vehicle to avoid approximately half of the collisions. An AEB system of the straight going vehicle was less effective. The effectiveness of the turning vehicle's AEB system increases if spatial limitations for the collision-avoidance steering maneuver are known. Such information could be provided by sensors detecting free space in or around the road environment or geographical information shared via vehicle to cloud communication. AEB interventions rarely result in collision avoidance for turning vehicles with speeds above 40km/h or for straight going vehicles with speeds above 60km/h. State of the art field-of-views of forward looking sensing systems designed for AEB rear-end interventions are capable of addressing turning across path situations. Copyright © 2016 Elsevier Ltd. All rights reserved.

The importance of initial protection of conspicuous mutants for the coevolution of defense and aposematic signaling of the defense: a modeling study.

PubMed

Ruxton, Graeme D; Speed, Michael P; Broom, Mark

2007-09-01

Most models of the evolution of aposematic signaling assume (1) that the secondary defense being signaled is fixed, and (2) that conspicuous mutants arising in a population of defended individuals of cryptic appearance are initially protected from predation. Previous models of ours relaxed the first assumption, here we relax the second and compare with our earlier work to explore the consequences of initial protection from predation on the coevolution of secondary defense and aposematic signaling. As expected, we find that aposematic signaling evolves more easily if initial protection is available. Less obviously, the coevolved level of secondary defense should also be higher if initial protection is provided. Across species or populations, we predict that when initial protection occurs, then strength of aposematic signal should be correlated with the strength of the underlying secondary defense, whereas no such correlation should occur without initial protection. Finally, we demonstrate that species can invest heavily in a secondary defense and remain maximally cryptic (forgoing the advantages of aposematic signaling) and that within a species we should expect strong variation in appearance between populations but much less variation within populations. Hence, we demonstrate that whether conspicuous morphs receive initial protection from predation has powerful and potentially empirically detectible consequences for the coevolution of secondary defenses and aposematic signaling.

Spectroscopic evidence of β-turn in N-glycated peptidomimetics related to leucine-enkephalin

NASA Astrophysics Data System (ADS)

Vass, E.; Hollósi, M.; Kveder, M.; Kojić-Prodić, B.; Čudić, M.; Horvat, Š.

2000-11-01

The conformational differences caused by N-glycation of the amide bond in endogenous opioid pentapeptide leucine-enkephalin (Tyr-Gly-Gly-Phe-Leu) have been explored in solution using FTIR spectroscopy, NMR and molecular modelling. The compounds studied include protected and unprotected enkephalin analogues N-alkylated at the second (Gly 2) amino acid residue with a 6-deoxy- D-galactose moiety ( 1- 3). Comparison of the amide I component bands in the FTIR spectra, measured in trifluoroethanol (TFE), CHCl 3 and DMSO, revealed significant differences in the intensity as well as shifts in component band frequencies for glycopeptides 1- 3. We found that only the FTIR spectrum of the fully protected compound 1 indicated the presence of a higher population of β-turns, while the spectra of the partially protected and unprotected glycopeptides 2 and 3 reflected the dominance of unordered or open structures, with some low population of turns. The observed NOE connectivities in CDCl 3 for both isomers of the fully protected compound 1, the all-trans one and another with Tyr 1-Gly 2 peptide bond in cis conformation, indicate the presence of a β-like turn conformation. Molecular dynamics simulations of the glycopeptide 1 obtained by unconstrained energy minimization of trans- and cis- 1 shows that one of trans form conformations is consistent with β-turn whereas cis isomer has revealed less-compact turn.

49 CFR Appendix B to Part 218 - Statement of Agency Enforcement Policy on Blue Signal Protection for Utility Employees

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 4 2011-10-01 2011-10-01 false Statement of Agency Enforcement Policy on Blue... on Blue Signal Protection for Utility Employees The following examples of the application of the train or yard crew exclusion from required blue signal protection for utility employees are provided to...

49 CFR Appendix B to Part 218 - Statement of Agency Enforcement Policy on Blue Signal Protection for Utility Employees

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 4 2013-10-01 2013-10-01 false Statement of Agency Enforcement Policy on Blue... on Blue Signal Protection for Utility Employees The following examples of the application of the train or yard crew exclusion from required blue signal protection for utility employees are provided to...

49 CFR Appendix B to Part 218 - Statement of Agency Enforcement Policy on Blue Signal Protection for Utility Employees

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false Statement of Agency Enforcement Policy on Blue... on Blue Signal Protection for Utility Employees The following examples of the application of the train or yard crew exclusion from required blue signal protection for utility employees are provided to...

49 CFR Appendix B to Part 218 - Statement of Agency Enforcement Policy on Blue Signal Protection for Utility Employees

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 4 2014-10-01 2014-10-01 false Statement of Agency Enforcement Policy on Blue... on Blue Signal Protection for Utility Employees The following examples of the application of the train or yard crew exclusion from required blue signal protection for utility employees are provided to...

49 CFR Appendix B to Part 218 - Statement of Agency Enforcement Policy on Blue Signal Protection for Utility Employees

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 4 2012-10-01 2012-10-01 false Statement of Agency Enforcement Policy on Blue... on Blue Signal Protection for Utility Employees The following examples of the application of the train or yard crew exclusion from required blue signal protection for utility employees are provided to...

Neglect severity after left and right brain damage.

PubMed

Suchan, Julia; Rorden, Chris; Karnath, Hans-Otto

2012-05-01

While unilateral spatial neglect after left brain damage is undoubtedly less common than spatial neglect after a right hemisphere lesion, it is also assumed to be less severe. Here we directly test this latter hypothesis using a continuous measure of neglect severity: the so-called Center of Cancellation (CoC). Rorden and Karnath (2010) recently validated this index for right brain damaged neglect patients. A first aim of the present study was to evaluate this new measure for spatial neglect after left brain damage. In a group of 48 left-sided stroke patients with and without neglect, a score greater than -0.086 on the Bells Test and greater than -0.024 on the Letter Cancellation Task turned out to indicate neglect behavior for acute left brain damaged patients. A second aim was to directly compare the severity of spatial neglect after left versus right brain injury by using the new CoC measure. While neglect is less frequent following left than right hemisphere injury, we found that when this symptom occurs it is of similar severity in acute left brain injury as in patients after acute right brain injury. Copyright © 2012 Elsevier Ltd. All rights reserved.

Turn-off-on chemiluminescence determination of cyanide.

PubMed

Han, Suqin; Wang, Jianbo; Jia, Shize

2015-02-01

A flow injection chemiluminescence (FI-CL) method was developed for the determination of cyanide (CN(-) ) based on the recovered CL signal by Cu(2+) inhibiting a glutathione (GSH)-capped CdTe quantum dot (QD) and hydrogen peroxide system. In an alkaline medium, strong CL signals were observed from the reaction of CdTe QDs and H2O2 , and addition of Cu(2+) could cause significant CL inhibition of the CdTe QDs-H2O2 system. In the presence of CN(-) , Cu(2+) can be removed from the surface of CdTe QDs via the formation of particularly stable [Cu(CN)n ]((n-1)-) species, and the CL signal of the CdTe QDs-H2O2 system was efficiently recovered. Thus, the CL signals of CdTe QDs-H2O2 system were turned off and turned on by the addition of Cu(2+) and CN(-) , respectively. Further, the results showed that among the tested ions, only CN(-) could recover the CL signal, which suggested that the CdTe QDs-H2O2 -Cu(2+) CL system had highly selectivity for CN(-) . Under optimum conditions, the CL intensity and the concentration of CN(-) show a good linear relationship in the range 0.0-650.0 ng/mL (R(2)  = 0.9996). The limit of detection for CN(-) was 6.0 ng/mL (3σ). This method has been applied to detect CN(-) in river water and industrial wastewater with satisfactory results. Copyright © 2014 John Wiley & Sons, Ltd.

Protective effect of FK506 on myocardial ischemia/reperfusion injury by suppression of CaN and ASK1 signaling circuitry.

PubMed

Feng, Xing; Li, Jing; Liu, Jinyu; Jin, Minghua; Liu, Xiaomei; Du, Haiying; Zhang, Long; Sun, Zhiwei; Li, Xiaoguang

2011-03-01

We investigated protective effect of FK506 on rat hearts subjected to ischemia/reperfusion (I/R) injury by regulating CaN and ASK1. Wistar rats were divided into four groups: Ischemia/reperfusion group (I/R), FK506 + Ischemia/reperfusion group (FK506-I/R), sham group, and FK506 + sham group (FK506-sham). Ischemia/reperfusion was achieved by occluding left coronary artery for 30 min and subsequently reperfusing for 120 min. FK506 was administered 15 min before ischemia. Rats in sham group and FK506-sham group were operated only by placing a ligature around the coronary artery, and the blood supply was not blocked. I/R group showed a rapid increase in TUNEL-positive cells and high risks of histopathological changes in damaged cardiac tissues. FK506 reduced the infarct size and inhibited the activation of CaN enzyme in FK506-I/R group. Increase in Bcl-2/Bax ratio in FK506-IR group indicated that FK506 protected myocardium from apoptosis induced by IR. The activity of CaN and ASK1 protein level decreased significantly after I/R injury in FK506-treated I/R heart. FK506 suppresses the activation of CaN and ASK1 through CaN-mediated apoptosis pathway, and ASK1 negatively regulates CaN activity. Suppression of CaN and ASK1 signaling circuitry are involved in protective effect of FK506 on rat myocardium I/R injury.

AntogomiR-451 protects human gastric epithelial cells from ethanol via activating AMPK signaling.

PubMed

Zhu, Huanhuan; Zhang, Linjie; Xu, Jianmin; Zhu, Chunhua; Zhao, Hui; Zhu, Yongkang; Lv, Guoqiang

2018-02-26

The prevention and treatment efficiency of ethanol-induced gastric epithelial injury are not satisfied. We have previously shown that AMP-activated protein kinase (AMPK) activation exerts a pro-survival function in human gastric epithelial cells (GECs). miroRNA-451 ("miR-451")'s inhibitor, antagomiR-451, can activate AMPK signaling. In the present study, we show that forced-expression of antagomiR-451 via a lentiviral vector depleted miR-451, leading to AMPK activation in established GES-1 cells and primary human GECs. AntagomiR-451 efficiently protected GES-1 cells and primary human GECs from ethanol-induced viability reduction and apoptosis. AMPK activation is required for antagomiR-451-induced GEC protection. AMPKα1 knockdown (by targeted-shRNAs) or knockout (by CRISPR-Cas-9 KO plasmid) blocked antagomiR-451-induced AMPK activation, and GEC protection against ethanol. Further experimental results show that antagomiR-451 significantly attenuated ethanol-induced reactive oxygen species (ROS) production, lipid peroxidation and DNA damage. Collectively, antagomiR-451 protects human GECs from ethanol via activating AMPK signaling. Copyright © 2018 Elsevier Inc. All rights reserved.

The effect of right-turn-on-red on pedestrian and bicyclist accidents

DOT National Transportation Integrated Search

1981-10-01

Right-Turn-On-Red (RTOR) in its "Western" or "permissive" version allows motorists to turn right on a red signal after stopping unless prohibited by a sign. Many states adopted Western RTOR in the mid-1970's. The objectives of this study were to ases...

Time to turn the other cheek? The influence of left and right poses on perceptions of academic specialisation.

PubMed

Lindell, Annukka K; Savill, Nicola J

2010-11-01

The human face expresses emotion asymmetrically. Whereas the left cheek is more emotionally expressive, the right cheek appears more impassive, hence the appropriate cheek to put forward depends on the circumstance. Nicholls, Clode, Wood, and Wood (1999, Proceedings of the Royal Society (Section B), 266, 1517-1522) demonstrated that people posing for family portraits offer the left cheek, whereas those posing as a Royal Society scientist favour the right. Given that the stereotypical representations of members of different academic disciplines differ markedly in their perceived openness and emotionality (e.g., "serious" scientist vs. "creative" writer), we reasoned that people may use cheek as a cue when determining a model's area of academic interest. Two hundred and nine participants (M=90, F=119) viewed pairs of left and right cheek poses, and made a forced-choice decision indicating which image depicted a Chemistry, Psychology or English student. Half the images were mirror-reversed to control for perceptual and aesthetic biases. Consistent with prediction, participants were more likely to select left cheek images for English students, and right cheek images for Chemistry students, irrespective of image orientation. The results confirm that determining the best cheek to put forward depends on your academic expertise: an impassive right cheek suggests hard science, whereas an emotive left cheek implies the arts. Psychology produced no left or right bias, consistent with its position as a discipline perpetually straddling the boundary between art and science.

Dual turn-on fluorescence signal-based controlled release system for real-time monitoring of drug release dynamics in living cells and tumor tissues.

PubMed

Kong, Xiuqi; Dong, Baoli; Song, Xuezhen; Wang, Chao; Zhang, Nan; Lin, Weiying

2018-01-01

Controlled release systems with capabilities for direct and real-time monitoring of the release and dynamics of drugs in living systems are of great value for cancer chemotherapy. Herein, we describe a novel dual turn-on fluorescence signal-based controlled release system ( CDox ), in which the chemotherapy drug doxorubicin ( Dox ) and the fluorescent dye ( CH ) are conjugated by a hydrazone moiety, a pH-responsive cleavable linker. CDox itself shows nearly no fluorescence as the fluorescence of CH and Dox is essentially quenched by the C=N isomerization and N-N free rotation. However, when activated under acidic conditions, CDox could be hydrolyzed to afford Dox and CH , resulting in dual turn-on signals with emission peaks at 595 nm and 488 nm, respectively. Notably, CDox exhibits a desirable controlled release feature as the hydrolysis rate is limited by the steric hindrance effect from both the Dox and CH moieties. Cytotoxicity assays indicate that CDox shows much lower cytotoxicity relative to Dox , and displays higher cell inhibition rate to cancer than normal cells. With the aid of the dual turn-on fluorescence at different wavelengths, the drug release dynamics of CDox in living HepG2 and 4T-1 cells was monitored in double channels in a real-time fashion. Importantly, two-photon fluorescence imaging of CDox in living tumor tissues was also successfully performed by high-definition 3D imaging. We expect that the unique controlled release system illustrated herein could provide a powerful means to investigate modes of action of drugs, which is critical for development of much more robust and effective chemotherapy drugs.

Dynamic change of ERPs related to selective attention to signals from left and right visual field during head-down tilt

NASA Astrophysics Data System (ADS)

Wei, Jinhe; Zhao, Lun; Van, Gongdong; Chen, Wenjuan; Ren, Wei; Duan, Ran

To study further the effect of head-down tilt(HDT) on slow positive potential in the event-related potentials(ERPs), the temporal and spatial features of visual ERPs changes during 2 hour HDT(-10 °) were compared with that during HUT(+20°) in 15 normal subjects. The stimuli were consisted of two color LED flashes appeared randomly in left or right visual field(LVF or RVF) with same probability. The subjects were asked to make switch response to target signals(T) differentially: switching to left for T in LVF and to right for T in RVF, ignoring non-target signals(N). Five sets of tests were made during HUT and HDT. ERPs were obtained from 9 locations on scalp. The mean value of the ERPs in the period from 0.32-0.55 s was taken as the amplitude of slow positive potential(P400). The main results were as follows. 1)The mean amplitude of P400 decreased during HDT which was more significant at the 2nd, 3rd and 5th set of tests; 2)spatially, the reduction of mean P400 amplitude during HDT was more significant for signals from RVF and was more significant at posterior and central brain regions than that on frontal locations. As that the positive potential probably reflects the active inhibition activity in the brain during attention process, these data provide further evidence showing that the higher brain function was affected by the simulated weightlessness and that this effect was not only transient but also with interesting spatial characteristics.

Coenzyme Q10 protects neural stem cells against hypoxia by enhancing survival signals.

PubMed

Park, Jinse; Park, Hyun-Hee; Choi, Hojin; Kim, Young Seo; Yu, Hyun-Jeung; Lee, Kyu-Yong; Lee, Young Joo; Kim, Seung Hyun; Koh, Seong-Ho

2012-10-10

Recanalization and secondary prevention are the main therapeutic strategies for acute ischemic stroke. Neuroprotective therapies have also been investigated despite unsuccessful clinical results. Coenzyme Q10 (CoQ10), which is an essential cofactor for electron transport in mitochondria, is known to have an antioxidant effect. We investigated the protective effects of CoQ10 against hypoxia in neural stem cells (NSCs). We measured cell viability and levels of intracellular signaling proteins after treatment with several concentrations of CoQ10 under hypoxia-reperfusion. CoQ10 protected NSCs against hypoxia-reperfusion in a concentration-dependent manner by reducing growth inhibition and inhibiting free radical formation. It increased the expression of a number of survival-related proteins such as phosphorylated Akt (pAkt), phosphorylated glycogen synthase kinase 3-β (pGSK3-β), and B-cell lymphoma 2 (Bcl-2) in NSCs injured by hypoxia-reperfusion and reduced the expression of death-related proteins such as cleaved caspase-3. We conclude that CoQ10 has effects against hypoxia-reperfusion induced damage to NSCs by enhancing survival signals and decreasing death signals. Copyright © 2012 Elsevier B.V. All rights reserved.

Signalling pathways and mechanisms of protection in pre- and postconditioning: historical perspective and lessons for the future

PubMed Central

Cohen, Michael V; Downey, James M

2015-01-01

Ischaemic pre- and postconditioning are potent cardioprotective interventions that spare ischaemic myocardium and decrease infarct size after periods of myocardial ischaemia/reperfusion. They are dependent on complex signalling pathways involving ligands released from ischaemic myocardium, G-protein-linked receptors, membrane growth factor receptors, phospholipids, signalling kinases, NO, PKC and PKG, mitochondrial ATP-sensitive potassium channels, reactive oxygen species, TNF-α and sphingosine-1-phosphate. The final effector is probably the mitochondrial permeability transition pore and the signalling produces protection by preventing pore formation. Many investigators have worked to produce a roadmap of this signalling with the hope that it would reveal where one could intervene to therapeutically protect patients with acute myocardial infarction whose hearts are being reperfused. However, attempts to date to show efficacy of such an intervention in large clinical trials have been unsuccessful. Reasons for this inability to translate successes in the experimental laboratory to the clinical arena are evaluated in this review. It is suggested that all patients with acute coronary syndromes currently presenting to the hospital and being treated with platelet P2Y12 receptor antagonists, the current standard of care, are indeed already benefiting from protection from the conditioning pathways outlined earlier. If that proves to be the case, then future attempts to further decrease infarction will have to rely on interventions which protect by a different mechanism. PMID:25205071

Signalling pathways and mechanisms of protection in pre- and postconditioning: historical perspective and lessons for the future.

PubMed

Cohen, Michael V; Downey, James M

2015-04-01

Ischaemic pre- and postconditioning are potent cardioprotective interventions that spare ischaemic myocardium and decrease infarct size after periods of myocardial ischaemia/reperfusion. They are dependent on complex signalling pathways involving ligands released from ischaemic myocardium, G-protein-linked receptors, membrane growth factor receptors, phospholipids, signalling kinases, NO, PKC and PKG, mitochondrial ATP-sensitive potassium channels, reactive oxygen species, TNF-α and sphingosine-1-phosphate. The final effector is probably the mitochondrial permeability transition pore and the signalling produces protection by preventing pore formation. Many investigators have worked to produce a roadmap of this signalling with the hope that it would reveal where one could intervene to therapeutically protect patients with acute myocardial infarction whose hearts are being reperfused. However, attempts to date to show efficacy of such an intervention in large clinical trials have been unsuccessful. Reasons for this inability to translate successes in the experimental laboratory to the clinical arena are evaluated in this review. It is suggested that all patients with acute coronary syndromes currently presenting to the hospital and being treated with platelet P2Y12 receptor antagonists, the current standard of care, are indeed already benefiting from protection from the conditioning pathways outlined earlier. If that proves to be the case, then future attempts to further decrease infarction will have to rely on interventions which protect by a different mechanism. © 2014 The British Pharmacological Society.

Depressive symptoms and negative life events: What psycho-social factors protect or harm left-behind children in China?

PubMed

Guang, Yu; Feng, Zhengzhi; Yang, Guoyu; Yang, Yaling; Wang, Lifei; Dai, Qin; Hu, Chaobing; Liu, Keyu; Zhang, Rui; Xia, Fan; Zhao, Mengxue

2017-12-15

In China, children under 18 years old who are left at rural residences for at least 6 months by either one or both of their parents migrating to work in cities are called "left-behind children (LBC)". Due to restricted family support, they are at a greater risk of developing depressive symptoms than non-left-behind children (NLBC). The objective of this study is to explore how depressive symptoms and stress induced by negative life events such as interpersonal conflicts, punishment and loss, as well as their relationships vary for LBC with different left-behind-related characteristics. Using data from a large school-based survey conducted in Chongqing between December 2012 and June 2013, we first identified the differences in depressive symptoms and negative-event-induced stress between LBC and NLBC, and then analyzed the variances among LBC with different left-behind-related characteristics. The data was analyzed with Chi-square test, MANCOVA, ANCOVA, ANOVA, T-test and hierarchical multiple regression analyses. We found that LBC were more stressed when experiencing negative events and had more depressive symptoms than NLBC. Children left behind by both parents were most depressed. Negative-event-induced stress and communication on life difficulties with migrant parents were risk factors for depressive symptoms, whereas adequate communication on academic performance or children's feelings was a protective factor against depressive symptoms. Communication duration and frequency, communication by visiting, communication on academic performance, life difficulties and children's feelings moderated the relationship between stress and depressive symptoms, respectively. Duration of separation, communication duration and frequency, communication on academic performance, learning difficulties and children's feelings moderated the relation between the type of parental migration and depressive symptoms, respectively. Our findings suggest that children left behind by both

Cost-Effectiveness of Percutaneous Closure of the Left Atrial Appendage in Atrial Fibrillation Based on Results From PROTECT AF Versus PREVAIL.

PubMed

Freeman, James V; Hutton, David W; Barnes, Geoffrey D; Zhu, Ruo P; Owens, Douglas K; Garber, Alan M; Go, Alan S; Hlatky, Mark A; Heidenreich, Paul A; Wang, Paul J; Al-Ahmad, Amin; Turakhia, Mintu P

2016-06-01

Randomized trials of left atrial appendage (LAA) closure with the Watchman device have shown varying results, and its cost effectiveness compared with anticoagulation has not been evaluated using all available contemporary trial data. We used a Markov decision model to estimate lifetime quality-adjusted survival, costs, and cost effectiveness of LAA closure with Watchman, compared directly with warfarin and indirectly with dabigatran, using data from the long-term (mean 3.8 year) follow-up of Percutaneous Closure of the Left Atrial Appendage Versus Warfarin Therapy for Prevention of Stroke in Patients With Atrial Fibrillation (PROTECT AF) and Prospective Randomized Evaluation of the Watchman LAA Closure Device in Patients With Atrial Fibrillation (PREVAIL) randomized trials. Using data from PROTECT AF, the incremental cost-effectiveness ratios compared with warfarin and dabigatran were $20 486 and $23 422 per quality-adjusted life year, respectively. Using data from PREVAIL, LAA closure was dominated by warfarin and dabigatran, meaning that it was less effective (8.44, 8.54, and 8.59 quality-adjusted life years, respectively) and more costly. At a willingness-to-pay threshold of $50 000 per quality-adjusted life year, LAA closure was cost effective 90% and 9% of the time under PROTECT AF and PREVAIL assumptions, respectively. These results were sensitive to the rates of ischemic stroke and intracranial hemorrhage for LAA closure and medical anticoagulation. Using data from the PROTECT AF trial, LAA closure with the Watchman device was cost effective; using PREVAIL trial data, Watchman was more costly and less effective than warfarin and dabigatran. PROTECT AF enrolled more patients and has substantially longer follow-up time, allowing greater statistical certainty with the cost-effectiveness results. However, longer-term trial results and postmarketing surveillance of major adverse events will be vital to determining the value of the Watchman in clinical

Turning Noise into Signal: Utilizing Impressed Pipeline Currents for EM Exploration

NASA Astrophysics Data System (ADS)

Lindau, Tobias; Becken, Michael

2017-04-01

Impressed Current Cathodic Protection (ICCP) systems are extensively used for the protection of central Europe's dense network of oil-, gas- and water pipelines against destruction by electrochemical corrosion. While ICCP systems usually provide protection by injecting a DC current into the pipeline, mandatory pipeline integrity surveys demand a periodical switching of the current. Consequently, the resulting time varying pipe currents induce secondary electric- and magnetic fields in the surrounding earth. While these fields are usually considered to be unwanted cultural noise in electromagnetic exploration, this work aims at utilizing the fields generated by the ICCP system for determining the electrical resistivity of the subsurface. The fundamental period of the switching cycles typically amounts to 15 seconds in Germany and thereby roughly corresponds to periods used in controlled source EM applications (CSEM). For detailed studies we chose an approximately 30km long pipeline segment near Herford, Germany as a test site. The segment is located close to the southern margin of the Lower Saxony Basin (LSB) and part of a larger gas pipeline composed of multiple segments. The current injected into the pipeline segment originates in a rectified 50Hz AC signal which is periodically switched on and off. In contrast to the usual dipole sources used in CSEM surveys, the current distribution along the pipeline is unknown and expected to be non-uniform due to coating defects that cause current to leak into the surrounding soil. However, an accurate current distribution is needed to model the fields generated by the pipeline source. We measured the magnetic fields at several locations above the pipeline and used Biot-Savarts-Law to estimate the currents decay function. The resulting frequency dependent current distribution shows a current decay away from the injection point as well as a frequency dependent phase shift which is increasing with distance from the injection

L&D Manual Turn Lane Storage Validation/Update

DOT National Transportation Integrated Search

2012-08-01

Queuing occurs at intersections mostly due to overflow or inadequacy of turn bays. The ODOT L&D : Manual Volume 1 has storage requirements for both signalized and unsignalized intersections. Figures : 401-9E and 401-10E of the L&D Manual provide the ...

A Driving Simulator Evaluation of Red Arrows and Flashing Yellow Arrows in Right-Turn Applications : Establishing the Foundation for Future Research

DOT National Transportation Integrated Search

2017-11-01

Driver understanding of flashing yellow arrow (FYA) indications for left turns has been studied extensively; however, the use of FYA for right-turn applications is an area that needs to be better understood through evaluations focused on actual drive...

Anticipation in turn-taking: mechanisms and information sources.

PubMed

Riest, Carina; Jorschick, Annett B; de Ruiter, Jan P

2015-01-01

During conversations participants alternate smoothly between speaker and hearer roles with only brief pauses and overlaps. There are two competing types of accounts about how conversationalists accomplish this: (a) the signaling approach and (b) the anticipatory ('projection') approach. We wanted to investigate, first, the relative merits of these two accounts, and second, the relative contribution of semantic and syntactic information to the timing of next turn initiation. We performed three button-press experiments using turn fragments taken from natural conversations to address the following questions: (a) Is turn-taking predominantly based on anticipation or on reaction, and (b) what is the relative contribution of semantic and syntactic information to accurate turn-taking. In our first experiment we gradually manipulated the information available for anticipation of the turn end (providing information about the turn end in advance to completely removing linguistic information). The results of our first experiment show that the distribution of the participants' estimation of turn-endings for natural turns is very similar to the distribution for pure anticipation. We conclude that listeners are indeed able to anticipate a turn-end and that this strategy is predominantly used in turn-taking. In Experiment 2 we collected purely reacted responses. We used the distributions from Experiments 1 and 2 together to estimate a new dependent variable called Reaction Anticipation Proportion. We used this variable in our third experiment where we manipulated the presence vs. absence of semantic and syntactic information by low-pass filtering open-class and closed class words in the turn. The results suggest that for turn-end anticipation, both semantic and syntactic information are needed, but that the semantic information is a more important anticipation cue than syntactic information.

Anticipation in turn-taking: mechanisms and information sources

PubMed Central

Riest, Carina; Jorschick, Annett B.; de Ruiter, Jan P.

2015-01-01

During conversations participants alternate smoothly between speaker and hearer roles with only brief pauses and overlaps. There are two competing types of accounts about how conversationalists accomplish this: (a) the signaling approach and (b) the anticipatory (‘projection’) approach. We wanted to investigate, first, the relative merits of these two accounts, and second, the relative contribution of semantic and syntactic information to the timing of next turn initiation. We performed three button-press experiments using turn fragments taken from natural conversations to address the following questions: (a) Is turn-taking predominantly based on anticipation or on reaction, and (b) what is the relative contribution of semantic and syntactic information to accurate turn-taking. In our first experiment we gradually manipulated the information available for anticipation of the turn end (providing information about the turn end in advance to completely removing linguistic information). The results of our first experiment show that the distribution of the participants’ estimation of turn-endings for natural turns is very similar to the distribution for pure anticipation. We conclude that listeners are indeed able to anticipate a turn-end and that this strategy is predominantly used in turn-taking. In Experiment 2 we collected purely reacted responses. We used the distributions from Experiments 1 and 2 together to estimate a new dependent variable called Reaction Anticipation Proportion. We used this variable in our third experiment where we manipulated the presence vs. absence of semantic and syntactic information by low-pass filtering open-class and closed class words in the turn. The results suggest that for turn-end anticipation, both semantic and syntactic information are needed, but that the semantic information is a more important anticipation cue than syntactic information. PMID:25699004

Notch/Her12 signalling modulates, motile/immotile cilia ratio downstream of Foxj1a in zebrafish left-right organizer

PubMed Central

Sampaio, Pedro; Pestana, Sara; Pinto, Andreia; Vaz, Andreia; Roxo-Rosa, Mónica; Gardner, Rui; Lopes, Telma; Schilling, Britta; Henry, Ian; Saúde, Leonor

2017-01-01

Foxj1a is necessary and sufficient to specify motile cilia. Using transcriptional studies and slow-scan two-photon live imaging capable of identifying the number of motile and immotile cilia, we now established that the final number of motile cilia depends on Notch signalling (NS). We found that despite all left-right organizer (LRO) cells express foxj1a and the ciliary axonemes of these cells have dynein arms, some cilia remain immotile. We identified that this decision is taken early in development in the Kupffer’s Vesicle (KV) precursors the readout being her12 transcription. We demonstrate that overexpression of either her12 or Notch intracellular domain (NICD) increases the number of immotile cilia at the expense of motile cilia, and leads to an accumulation of immotile cilia at the anterior half of the KV. This disrupts the normal fluid flow intensity and pattern, with consequent impact on dand5 expression pattern and left-right (L-R) axis establishment. PMID:28875937

Regulator of G Protein Signaling 6 Protects the Heart from Ischemic Injury

PubMed Central

Chakravarti, Bandana; Mabe, Nathaniel W.; Seeley, Sarah L.; Bui, Albert D.; Yang, Jianqi; Watts, Stephanie W.; Neubig, Richard R.; Fisher, Rory A.

2017-01-01

Gαi-coupled receptors play important roles in protecting the heart from ischemic injury. Regulator of G protein signaling (RGS) proteins suppress Gαi signaling by accelerating the GTPase activity of Gαi subunits. However, the roles of individual RGS proteins in modulating ischemic injury are unknown. In this study, we investigated the effect of RGS6 deletion on myocardial sensitivity to ischemic injury. Hearts from RGS6 knockout (RGS6−/−) and RGS6 wild-type (RGS6+/+) mice were subjected to 30 minutes of ischemia and 2 hours of reperfusion on a Langendorff heart apparatus. Infarcts in RGS6−/− hearts were significantly larger than infarcts in RGS6+/+ hearts. RGS6−/− hearts also exhibited increased phosphorylation of β2-adrenergic receptors and G protein–coupled receptor kinase 2 (GRK2). Mitochondrial GRK2 as well as caspase-3 cleavage were increased significantly in RGS6−/− hearts compared with RGS6+/+ hearts after ischemia. Chronic propranolol treatment of mice prevented the observed increases in ischemic injury and the GRK2 phosphorylation observed in RGS6−/− hearts. Our findings suggest that loss of RGS6 predisposes the ventricle to prodeath signaling through a β2AR-GRK2–dependent signaling mechanism, and they provide evidence for a protective role of RGS6 in the ischemic heart. Individuals expressing genetic polymorphisms that suppress the activity of RGS6 may be at increased risk of cardiac ischemic injury. Furthermore, the development of agents that increase RGS6 expression or activity might provide a novel strategy for the treatment of ischemic heart disease. PMID:28035008

ERK1/2 signalling protects against apoptosis following endoplasmic reticulum stress but cannot provide long-term protection against BAX/BAK-independent cell death.

PubMed

Darling, Nicola J; Balmanno, Kathryn; Cook, Simon J

2017-01-01

Disruption of protein folding in the endoplasmic reticulum (ER) causes ER stress. Activation of the unfolded protein response (UPR) acts to restore protein homeostasis or, if ER stress is severe or persistent, drive apoptosis, which is thought to proceed through the cell intrinsic, mitochondrial pathway. Indeed, cells that lack the key executioner proteins BAX and BAK are protected from ER stress-induced apoptosis. Here we show that chronic ER stress causes the progressive inhibition of the extracellular signal-regulated kinase (ERK1/2) signalling pathway. This is causally related to ER stress since reactivation of ERK1/2 can protect cells from ER stress-induced apoptosis whilst ERK1/2 pathway inhibition sensitises cells to ER stress. Furthermore, cancer cell lines harbouring constitutively active BRAFV600E are addicted to ERK1/2 signalling for protection against ER stress-induced cell death. ERK1/2 signalling normally represses the pro-death proteins BIM, BMF and PUMA and it has been proposed that ER stress induces BIM-dependent cell death. We found no evidence that ER stress increased the expression of these proteins; furthermore, BIM was not required for ER stress-induced death. Rather, ER stress caused the PERK-dependent inhibition of cap-dependent mRNA translation and the progressive loss of pro-survival proteins including BCL2, BCLXL and MCL1. Despite these observations, neither ERK1/2 activation nor loss of BAX/BAK could confer long-term clonogenic survival to cells exposed to ER stress. Thus, ER stress induces cell death by at least two biochemically and genetically distinct pathways: a classical BAX/BAK-dependent apoptotic response that can be inhibited by ERK1/2 signalling and an alternative ERK1/2- and BAX/BAK-independent cell death pathway.

You cannot speak and listen at the same time: a probabilistic model of turn-taking.

PubMed

Donnarumma, Francesco; Dindo, Haris; Iodice, Pierpaolo; Pezzulo, Giovanni

2017-04-01

Turn-taking is a preverbal skill whose mastering constitutes an important precondition for many social interactions and joint actions. However, the cognitive mechanisms supporting turn-taking abilities are still poorly understood. Here, we propose a computational analysis of turn-taking in terms of two general mechanisms supporting joint actions: action prediction (e.g., recognizing the interlocutor's message and predicting the end of turn) and signaling (e.g., modifying one's own speech to make it more predictable and discriminable). We test the hypothesis that in a simulated conversational scenario dyads using these two mechanisms can recognize the utterances of their co-actors faster, which in turn permits them to give and take turns more efficiently. Furthermore, we discuss how turn-taking dynamics depend on the fact that agents cannot simultaneously use their internal models for both action (or messages) prediction and production, as these have different requirements-or, in other words, they cannot speak and listen at the same time with the same level of accuracy. Our results provide a computational-level characterization of turn-taking in terms of cognitive mechanisms of action prediction and signaling that are shared across various interaction and joint action domains.

Digital signal processing the Tevatron BPM signals

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

Cancelo, G.; James, E.; Wolbers, S.

2005-05-01

The Beam Position Monitor (TeV BPM) readout system at Fermilab's Tevatron has been updated and is currently being commissioned. The new BPMs use new analog and digital hardware to achieve better beam position measurement resolution. The new system reads signals from both ends of the existing directional stripline pickups to provide simultaneous proton and antiproton measurements. The signals provided by the two ends of the BPM pickups are processed by analog band-pass filters and sampled by 14-bit ADCs at 74.3MHz. A crucial part of this work has been the design of digital filters that process the signal. This paper describesmore » the digital processing and estimation techniques used to optimize the beam position measurement. The BPM electronics must operate in narrow-band and wide-band modes to enable measurements of closed-orbit and turn-by-turn positions. The filtering and timing conditions of the signals are tuned accordingly for the operational modes. The analysis and the optimized result for each mode are presented.« less

Kinematics and muscle activity of the head, lumbar and knee joints during 180° turning and sitting down task in older adults.

PubMed

Kuo, Fang-Chuan; Hong, Chang-Zern; Liau, Ben-Yi

2014-01-01

The "180° turning and sitting down task" is a very conscious movement that requires focusing on turning at the exact moment, and very few studies address on this topic in older adults. The purpose of the study was to compare kinematics and electromyography of the head, lumbar and knee joints during 180°turning in older and young adults. Twenty older adults and 20 younger adults were assessed. A 16-channel telemetry electromyography system with electrogoniometers and an inclinometer were used to record the head, lumbar and knee joint kinematic and electromyography data during the 180° turning. This movement had been further divided into 4 phases (braking, mid-stance, swing, and terminal loading) for analysis. There were significant differences in the joint displacement and muscular activity among the different phases. Comparison between groups showed that the older adults group had less lateral lumbar flexion, less knee flexion and lower velocity of the head and knee flexion compared to young adults during turning. The electromyography data of the left biceps femoris, left gastrocnemius and left erector spinae muscles in the older adults group showed significantly higher levels than in the young adults. Older adults need to adjust velocities of moving joints and increase the extensor synergy muscles of the back and the stance leg to provide posture stability. Kinematics and neuromuscular modulations of the head, lumbar and knee are required according to the various phases of the turn movements and change with aging. © 2013.

Delta-Tocotrienol Protects Mouse and Human Hematopoietic Progenitors from Gamma-Irradiation Through Erk/mTOR Signaling

DTIC Science & Technology

2010-01-01

δ- tocotrienol protects mouse and human hematopoietic progenitors from γ-irradiation through Erk/mTOR signaling by Xiang Hong Li, Dadin Fu, Nabil H...print] Citation: Li XH, Fu D, Latif NH, Mullaney CP, Ney PH, Mog SR, Whitnall MH, Srinivasan V, and Xiao M. δ- tocotrienol protects mouse and human...2010 2. REPORT TYPE 3. DATES COVERED 00-00-2010 to 00-00-2010 4. TITLE AND SUBTITLE !- tocotrienol protects mouse and human hematopoietic

Electronic circuit detects left ventricular ejection events in cardiovascular system

NASA Technical Reports Server (NTRS)

Gebben, V. D.; Webb, J. A., Jr.

1972-01-01

Electronic circuit processes arterial blood pressure waveform to produce discrete signals that coincide with beginning and end of left ventricular ejection. Output signals provide timing signals for computers that monitor cardiovascular systems. Circuit operates reliably for heart rates between 50 and 200 beats per minute.

The cochlear CRF signaling systems and their mechanisms of action in modulating cochlear sensitivity and protection against trauma

PubMed Central

Graham, Christine E.; Basappa, Johnvesly; Turcan, Sevin; Vetter, Douglas E.

2011-01-01

A key requirement for encoding the auditory environment is the ability to dynamically alter cochlear sensitivity. However, merely attaining a steady state of maximal sensitivity is not a viable solution since the sensory cells and ganglion cells of the cochlea are prone to damage following exposure to loud sound. Most often, such damage is via initial metabolic insult that can lead to cellular death. Thus, establishing the highest sensitivity must be balanced with protection against cellular metabolic damage that can lead to loss of hair cells and ganglion cells, resulting in loss of frequency representation. While feedback mechanisms are known to exist in the cochlea that alter sensitivity, they respond only after stimulus encoding, allowing potentially damaging sounds to impact the inner ear at times coincident with increased sensitivity. Thus, questions remain concerning the endogenous signaling systems involved in dynamic modulation of cochlear sensitivity and protection against metabolic stress. Understanding endogenous signaling systems involved in cochlear protection may lead to new strategies and therapies for prevention of cochlear damage and consequent hearing loss. We have recently discovered a novel cochlear signaling system that is molecularly equivalent to the classic hypothalamic-pituitary-adrenal (HPA) axis. This cochlear HPA-equivalent system functions to balance auditory sensitivity and susceptibility to noise-induced hearing loss, and also protects against cellular metabolic insults resulting from exposures to ototoxic drugs. We review the anatomy, physiology, and cellular signaling of this system, and compare it to similar signaling in other organs/tissues of the body. PMID:21909974

Left-right asymmetry and cardiac looping: implications for cardiac development and congenital heart disease.

PubMed

Kathiriya, I S; Srivastava, D

2000-01-01

Proper morphogenesis and positioning of internal organs requires delivery and interpretation of precise signals along the anterior-posterior, dorsal-ventral, and left-right axes. An elegant signaling cascade determines left- versus right-sided identity in visceral organs in a concordant fashion, resulting in a predictable left-right (LR) organ asymmetry in all vertebrates. The complex morphogenesis of the heart and its connections to the vasculature are particularly dependent upon coordinated LR signaling pathways. Disorganization of LR signals can result in myriad congenital heart defects that are a consequence of abnormal looping and remodeling of the primitive heart tube into a multi-chambered organ. A framework for understanding how LR asymmetric signals contribute to normal organogenesis has emerged and begins to explain the basis of many human diseases of LR asymmetry. Here we review the impact of LR signaling pathways on cardiac development and congenital heart disease.

MyD88 signaling inhibits protective immunity to the gastrointestinal helminth parasite Heligmosomoides polygyrus.

PubMed

Reynolds, Lisa A; Harcus, Yvonne; Smith, Katherine A; Webb, Lauren M; Hewitson, James P; Ross, Ewan A; Brown, Sheila; Uematsu, Satoshi; Akira, Shizuo; Gray, David; Gray, Mohini; MacDonald, Andrew S; Cunningham, Adam F; Maizels, Rick M

2014-09-15

Helminth parasites remain one of the most common causes of infections worldwide, yet little is still known about the immune signaling pathways that control their expulsion. C57BL/6 mice are chronically susceptible to infection with the gastrointestinal helminth parasite Heligmosomoides polygyrus. In this article, we report that C57BL/6 mice lacking the adapter protein MyD88, which mediates signaling by TLRs and IL-1 family members, showed enhanced immunity to H. polygyrus infection. Alongside increased parasite expulsion, MyD88-deficient mice showed heightened IL-4 and IL-17A production from mesenteric lymph node CD4(+) cells. In addition, MyD88(-/-) mice developed substantial numbers of intestinal granulomas around the site of infection, which were not seen in MyD88-sufficient C57BL/6 mice, nor when signaling through the adapter protein TRIF (TIR domain-containing adapter-inducing IFN-β adapter protein) was also ablated. Mice deficient solely in TLR2, TLR4, TLR5, or TLR9 did not show enhanced parasite expulsion, suggesting that these TLRs signal redundantly to maintain H. polygyrus susceptibility in wild-type mice. To further investigate signaling pathways that are MyD88 dependent, we infected IL-1R1(-/-) mice with H. polygyrus. This genotype displayed heightened granuloma numbers compared with wild-type mice, but without increased parasite expulsion. Thus, the IL-1R-MyD88 pathway is implicated in inhibiting granuloma formation; however, protective immunity in MyD88-deficient mice appears to be granuloma independent. Like IL-1R1(-/-) and MyD88(-/-) mice, animals lacking signaling through the type 1 IFN receptor (i.e., IFNAR1(-/-)) also developed intestinal granulomas. Hence, IL-1R1, MyD88, and type 1 IFN receptor signaling may provide pathways to impede granuloma formation in vivo, but additional MyD88-mediated signals are associated with inhibition of protective immunity in susceptible C57BL/6 mice. Copyright © 2014 The Authors.

Ribbon structure stabilized by C10 and C12 turns in αγ hybrid peptide.

PubMed

Wani, Naiem Ahmad; Kant, Rajni; Gupta, Vivek Kumar; Aravinda, Subrayashastry; Rai, Rajkishor

2016-04-01

The present study describes the synthesis and crystallographic analysis of αγ hybrid peptides, Boc-Gpn-L-Pro-NHMe (1), Boc-Aib-Gpn-L-Pro-NHMe (2), and Boc-L-Pro-Aib-Gpn-L-Pro-NHMe (3). Peptides 1 and 2 adopt expanded 12-membered (C12 ) helical turn over γα segment. Peptide 3 promotes the ribbon structure stabilized by type II β-turn (C10 ) followed by the expanded C12 helical γα turn. Both right-handed and left-handed helical conformations for Aib residue are observed in peptides 2 and 3, respectively. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd.

Lattice Calibration with Turn-By-Turn BPM Data

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

Huang, Xiaobiao; /SLAC; Sebek, James

2012-07-02

Turn-by-turn beam position monitor (BPM) data from multiple BPMs are fitted with a tracking code to calibrate magnet strengths in a manner similar to the well known LOCO code. Simulation shows that this turn-by-turn method can be a quick and efficient way for optics calibration. The method is applicable to both linacs and ring accelerators. Experimental results for a section of the SPEAR3 ring is also shown.

Winding a Long Coil with a Pre-Programmed Turns Density Variation

DTIC Science & Technology

1975-05-27

turns den- sity is to follow. A machine having this capability is needed to provide a towed ELF loop antenna with the smoothly tapered sensitivity...Introduction A submarine towed ELF loop antenna vibrates longitudinally and trans- versely during towing. The vibration is driven by the fluctuating surface...in attaining the smoothly varying turns density required for the signal winding of a towed ELF loop antenna . Acknowledgments Thanks are due to John

Yellow and the Novel Aposematic Signal, Red, Protect Delias Butterflies from Predators.

PubMed

Wee, Jocelyn Liang Qi; Monteiro, Antónia

2017-01-01

Butterflies of the South Asian and Australian genus Delias possess striking colours on the ventral wings that are presumed to serve as warning signals to predators. However, this has not been shown empirically. Here we experimentally tested whether the colours of one member of this diverse genus, Delias hyparete, function as aposematic signals. We constructed artificial paper models with either a faithful colour representation of D. hyparete, or with all of its colours converted to grey scale. We also produced models where single colours were left intact, while others were converted to grey-scale or removed entirely. We placed all model types simultaneously in the field, attached to a live mealworm, and measured relative attack rates at three separate field sites. Faithful models of D. hyparete, suffered the least amount of attacks, followed by grey-scale models with unaltered red patches, and by grey-scale models with unaltered yellow patches. We conclude that red and yellow colours function as warning signals. By mapping dorsal and ventral colouration onto a phylogeny of Delias, we observed that yellow and red colours appear almost exclusively on the ventral wing surfaces, and that basal lineages have mostly yellow, white, and black wings, whereas derived lineages contain red colour in addition to the other colours. Red appears to be, thus, a novel adaptive trait in this lineage of butterflies.

Yellow and the Novel Aposematic Signal, Red, Protect Delias Butterflies from Predators

PubMed Central

Wee, Jocelyn Liang Qi

2017-01-01

Butterflies of the South Asian and Australian genus Delias possess striking colours on the ventral wings that are presumed to serve as warning signals to predators. However, this has not been shown empirically. Here we experimentally tested whether the colours of one member of this diverse genus, Delias hyparete, function as aposematic signals. We constructed artificial paper models with either a faithful colour representation of D. hyparete, or with all of its colours converted to grey scale. We also produced models where single colours were left intact, while others were converted to grey-scale or removed entirely. We placed all model types simultaneously in the field, attached to a live mealworm, and measured relative attack rates at three separate field sites. Faithful models of D. hyparete, suffered the least amount of attacks, followed by grey-scale models with unaltered red patches, and by grey-scale models with unaltered yellow patches. We conclude that red and yellow colours function as warning signals. By mapping dorsal and ventral colouration onto a phylogeny of Delias, we observed that yellow and red colours appear almost exclusively on the ventral wing surfaces, and that basal lineages have mostly yellow, white, and black wings, whereas derived lineages contain red colour in addition to the other colours. Red appears to be, thus, a novel adaptive trait in this lineage of butterflies. PMID:28060944

Protective properties of sesamin against fluoride-induced oxidative stress and apoptosis in kidney of carp (Cyprinus carpio) via JNK signaling pathway.

PubMed

Cao, Jinling; Chen, Jianjie; Xie, Lingtian; Wang, Jundong; Feng, Cuiping; Song, Jing

2015-10-01

Sesamin, a major lignan derived from sesame seeds, has been reported to have many benefits and medicinal properties. However, its protective effects against fluoride-induced injury in kidney of fish have not been clarified. Previously we found that fluoride exposure caused damage and apoptosis in the kidneys of the common carp, Cyprinus carpio. In this study, the effects of sesamin on renal oxidative stress and apoptosis in fluoride-exposed fish were determined. The results showed that sesamin alleviated significantly fluoride-induced renal damage and apoptosis of carp in a dose-dependent manner, indicated by the histopathological examination and ultrastructural observation. Moreover, treatment with sesamin also inhibited significantly fluoride-induced remarkable enhancement of reactive oxygen species (ROS) production and oxidative stress, such as the increase of lipid peroxidation level and the depletion of intracellular reduced glutathione (GSH) level in kidney. To explore the underlying mechanisms of sesamin action, we found that activities of caspase-3 were notably inhibited by treatment with sesamin in the kidney of fluoride-exposed fish. Sesamin decreased the levels of p-JNK protein in kidney, which in turn inactivated pro-apoptotic signaling events by restoring the balance between mitochondrial pro- and anti-apoptotic Bcl-2 and Bax proteins and by decreasing the release of mitochondrial cytochrome c in kidney of fluoride-exposed fish. JNK was also involved in the mitochondrial extrinsic apoptotic pathways of sesamin effects against fluoride-induced renal injury by regulating the levels of p-c-Jun, necrosis factor-alpha (TNF-α) and Bak proteins. These findings indicated that sesamin could protect kidney against fluoride-induced apoptosis by the oxidative stress downstream-mediated change in the inactivation of JNK signaling pathway. Taken together, sesamin plays an important role in maintaining renal health and preventing kidney from toxic damage induced by

Triptolide induces protective autophagy through activation of the CaMKKβ-AMPK signaling pathway in prostate cancer cells.

PubMed

Zhao, Fei; Huang, Weiwei; Zhang, Zhe; Mao, Lin; Han, Yangyang; Yan, Jun; Lei, Ming

2016-02-02

Triptolide, an active compound extracted from the Chinese herb thunder god vine (Tripterygium wilfordii Hook F.), has potent anti-tumor activity. Recently, triptolide was found to induce autophagy in cancer cells. However, the effects of triptolide on autophagy in human prostate cancer (PCa) cells have not yet been clearly elucidated. In this study, we demonstrated that triptolide induces autophagy in three PCa cell lines, PC-3, LNCaP and C4-2. Furthermore, we found that triptolide mediates intracellular accumulation of free calcium by stimulating the endoplasmic reticulum (ER) stress response. This activates the CaMKKβ-AMPK signaling pathway, which in turn inhibits mTOR and activates both ULK1 and Beclin 1, finally resulting in autophagy. Moreover, we found that treatment with autophagy inhibitors 3-methyladenine (3-MA) and chloroquine (CQ) enhances triptolide-induced PCa cell death and growth inhibition. Using a PC-3-xenografted mouse model, we showed that blocking autophagy with CQ significantly promoted triptolide-induced tumor growth inhibition in vivo. Overall, our results show that triptolide induces protective autophagy through the CaMKKβ-AMPK pathway in PCa cells, implying that a combination of triptolide with autophagy inhibitors may potentially be an effective therapeutic strategy for PCa.

Unilateral dampening of Bmp activity by nodal generates cardiac left-right asymmetry.

PubMed

Veerkamp, Justus; Rudolph, Franziska; Cseresnyes, Zoltan; Priller, Florian; Otten, Cécile; Renz, Marc; Schaefer, Liliana; Abdelilah-Seyfried, Salim

2013-03-25

Signaling by Nodal and Bmp is essential for cardiac laterality. How activities of these pathways translate into left-right asymmetric organ morphogenesis is largely unknown. We show that, in zebrafish, Nodal locally reduces Bmp activity on the left side of the cardiac field. This effect is mediated by the extracellular matrix enzyme Hyaluronan synthase 2, expression of which is induced by Nodal. Unilateral reduction of Bmp signaling results in lower expression of nonmuscle myosin II and higher cell motility on the left, driving asymmetric displacement of the entire cardiac field. In silico modeling shows that left-right differences in cell motility are sufficient to induce a robust, directional migration of cardiac tissue. Thus, the mechanism underlying the formation of cardiac left-right asymmetry involves Nodal modulating an antimotogenic Bmp activity. Copyright © 2013 Elsevier Inc. All rights reserved.

Neurula rotation determines left-right asymmetry in ascidian tadpole larvae.

PubMed

Nishide, Kazuhiko; Mugitani, Michio; Kumano, Gaku; Nishida, Hiroki

2012-04-01

Tadpole larvae of the ascidian Halocynthia roretzi show morphological left-right asymmetry. The tail invariably bends towards the left side within the vitelline membrane. The structure of the larval brain is remarkably asymmetric. nodal, a conserved gene that shows left-sided expression, is also expressed on the left side in H. roretzi but in the epidermis unlike in vertebrates. We show that nodal signaling at the late neurula stage is required for stereotypic morphological left-right asymmetry at later stages. We uncover a novel mechanism to break embryonic symmetry, in which rotation of whole embryos provides the initial cue for left-sided expression of nodal. Two hours prior to the onset of nodal expression, the neurula embryo rotates along the anterior-posterior axis in a counterclockwise direction when seen in posterior view, and then this rotation stops when the left side of the embryo is oriented downwards. It is likely that epidermis monocilia, which appear at the neurula rotation stage, generate the driving force for the rotation. When the embryo lies on the left side, protrusion of the neural fold physically prevents it from rotating further. Experiments in which neurula rotation is perturbed by various means, including centrifugation and sandwiching between glass, indicate that contact of the left epidermis with the vitelline membrane as a consequence of neurula rotation promotes nodal expression in the left epidermis. We suggest that chemical, and not mechanical, signals from the vitelline membrane promote nodal expression. Neurula rotation is also conserved in other ascidian species.

A simulator-based analysis of engineering treatments for right-hook bicycle crashes at signalized intersections.

PubMed

Warner, Jennifer; Hurwitz, David S; Monsere, Christopher M; Fleskes, Kayla

2017-07-01

A right-hook crash is a crash between a right-turning motor vehicle and an adjacent through-moving bicycle. At signalized intersections, these crashes can occur during any portion of the green interval when conflicting bicycles and vehicles are moving concurrently. The objective of this research was to evaluate the effectiveness of four types of engineering countermeasures - regulatory signage, intersection pavement marking, smaller curb radius, and protected intersection design - at modifying driver behaviors that are known contributing factors in these crashes. This research focused on right-hook crashes that occur during the latter stage of the circular green indication at signalized intersections with a shared right-turn and through lane. Changes in driver performance in response to treatments were measured in a high-fidelity driving simulator. Twenty-eight participants each completed 22 right-turn maneuvers. A partially counterbalanced experimental design exposed drivers to critical scenarios, which had been determined in a previous experiment. For each turn, driver performance measures, including visual attention, crash avoidance, and potential crash severity, were collected. A total of 75 incidents (47 near-collisions and 28 collisions) were observed during the 616 right turns. All treatments had some positive effect on measured driver performance with respect to the right-turn vehicle conflicts. Further work is required to map the magnitude of these changes in driver performance to crash-based outcomes. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Clinical Significance Of Freezing While Turning in Parkinson’s Disease

PubMed Central

Mancini, Martina; Smulders, Katrijn; Cohen, Rajal G.; Horak, Fay B.; Giladi, Nir; Nutt, John G

2016-01-01

Freezing of gait (FoG) in people with Parkinson’s disease (PD) is an environmentally sensitive, intermittent problem that occurs most often during turning. FoG is difficult for clinicians to evaluate and treat because it can be difficult to elicit during a clinical visit. Here, we aimedto develop a clinically valid objective measure of freezing severity during a 2-minute 360 degrees turning-in-place. Twenty-eight subjects with PD (16 freezers, FoG+, and 12 nonfreezers, FoG−) in the “off” state and 14 healthy control subjects were tested. Subjects wore 3 inertial sensors (one on each shin and one on the waist) while 1) turning in place for 2 minutes (alternating 360 degrees to the right with 360 degrees to the left) and 2) performing an Instrumented 7m Timed Up and Go test (ITUG). Performance was videotaped, and clinical severity of FoG was independently rated by two movement disorders specialists (co-authors). Turning in place consistently resulted in FoG (13 out of 16 subjects with PD) while FoG was clinically observed in only 2 subjects with PD during the ITUG test. The Freezing Ratio during the turning test was significantly correlated with the clinical ratings (ρ=0.7, p=0.003) and with score on the new freezing of gait questionnaire (ρ=0.5, p=0.03). After correcting for symptom severity (UPDRS-III), out of the 4 objective measures of the turning test (total number of turns, average turn peak speed and average turn smoothness), only the Freezing Ratio was significantly different across groups (p=0.04). Freezing can be well quantified with body-worn inertial sensors during a 2-minute turning-in-place protocol. PMID:27956066

Road diet informational guide.

DOT National Transportation Integrated Search

2014-11-01

A classic Road Diet converts an existing four-lane undivided roadway segment to a three-lane segment consisting of two : through lanes and a center two-way left turn lane (TWLTL). A Road Diet improves safety by including a protected left-turn lane : ...

[Abnormal head turn in a patient with Brown's syndrome].

PubMed

van Waveren, M; Krzizok, T; Besch, D

2008-08-01

We report on an eight-year-old boy, who was presented in our clinic because of head turn. The cause of the tortecollis (ocular or general) in this case was and still cannot be explained. Only by applying extensive prism adaptation tests it was possible to prove the ocular character of the head turn. An eight-year-old boy with Brown's syndrome was referred to us because of a head tilt to the left side. Six months previously surgery on the M. obl. superior of the right eye was performed in another clinic. No improvement of the head tilt could be observed after the operation. In addition, an exotropia became decompensated. Under a 3-day occlusion of one eye, no change of the head turn and the squint could be measured. No other cause of the head turn could be found by an orthopaedist and a paediatrist. Under a prism of 20 cm/m basis in and 10 cm/m basis against the positive vertical deviation, the head tilt decreased, so that we decided to do a second surgery. The head tilting had not resumed at one year after the surgery. Although the initial diagnostic findings ruled out an ocular cause, it was possible to lessen the head tilting with the aid of the prism adaptation test. This case study emphasises the usefulness of a prism adaptation test of several days duration in order to validate an ocular cause of head turn and to determine an adequate indication for surgery.

Classification of functional near-infrared spectroscopy signals corresponding to the right- and left-wrist motor imagery for development of a brain-computer interface.

PubMed

Naseer, Noman; Hong, Keum-Shik

2013-10-11

This paper presents a study on functional near-infrared spectroscopy (fNIRS) indicating that the hemodynamic responses of the right- and left-wrist motor imageries have distinct patterns that can be classified using a linear classifier for the purpose of developing a brain-computer interface (BCI). Ten healthy participants were instructed to imagine kinesthetically the right- or left-wrist flexion indicated on a computer screen. Signals from the right and left primary motor cortices were acquired simultaneously using a multi-channel continuous-wave fNIRS system. Using two distinct features (the mean and the slope of change in the oxygenated hemoglobin concentration), the linear discriminant analysis classifier was used to classify the right- and left-wrist motor imageries resulting in average classification accuracies of 73.35% and 83.0%, respectively, during the 10s task period. Moreover, when the analysis time was confined to the 2-7s span within the overall 10s task period, the average classification accuracies were improved to 77.56% and 87.28%, respectively. These results demonstrate the feasibility of an fNIRS-based BCI and the enhanced performance of the classifier by removing the initial 2s span and/or the time span after the peak value. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Notch3/Akt signaling contributes to OSM-induced protection against cardiac ischemia/reperfusion injury.

PubMed

Zhang, Mingming; Wang, Chen; Hu, Jianqiang; Lin, Jie; Zhao, Zhijing; Shen, Min; Gao, Haokao; Li, Na; Liu, Min; Zheng, Pengfei; Qiu, Cuiting; Gao, Erhe; Wang, Haichang; Sun, Dongdong

2015-09-01

Oncostatin M (OSM) exhibits many unique biological activities by activating the Oβ receptor. However, its role in myocardial ischemia/reperfusion injury (I/R injury) in mice remains unknown. We investigated whether Notch3/Akt signaling is involved in the regulation of OSM-induced protection against cardiac I/R injury. The effects of OSM were assessed in mice that underwent myocardial I/R injury by OSM treatment or by genetic deficiency of the OSM receptor Oβ. We investigated its effects on cardiomyocyte apoptosis and mitochondrial biogenesis and whether Notch3/Akt signaling was involved in the regulation of OSM-induced protection against cardiac I/R injury. The mice underwent 30 min of ischemia followed by 3 h of reperfusion and were randomized to be treated with Notch3 siRNA (siNotch3) or lentivirus carrying Notch3 cDNA (Notch3) 72 h before coronary artery ligation. Myocardial infarct size, cardiac function, cardiomyocyte apoptosis and mitochondria morphology in mice that underwent cardiac I/R injury were compared between groups. OSM alleviated cardiac I/R injury by inhibiting cardiomyocyte apoptosis through promotion of Notch3 production, thus activating the PI3K/Akt pathway. OSM enhanced mitochondrial biogenesis and mitochondrial function in mice subjected to cardiac I/R injury. In contrast, OSM receptor Oβ knock out exacerbated cardiac I/R injury, decreased Notch3 production, enhanced cardiomyocyte apoptosis, and impaired mitochondrial biogenesis in cardiac I/R injured mice. The mechanism of OSM on cardiac I/R injury is partly mediated by the Notch3/Akt pathway. These results suggest a novel role of Notch3/Akt signaling that contributes to OSM-induced protection against cardiac I/R injury.

Disruption of sonic hedgehog signaling in Ellis-van Creveld dwarfism confers protection against bipolar affective disorder.

PubMed

Ginns, E I; Galdzicka, M; Elston, R C; Song, Y E; Paul, S M; Egeland, J A

2015-10-01

Ellis-van Creveld syndrome, an autosomal recessively inherited chondrodysplastic dwarfism, is frequent among Old Order Amish of Pennsylvania. Decades of longitudinal research on bipolar affective disorder (BPAD) revealed cosegregation of high numbers of EvC and Bipolar I (BPI) cases in several large Amish families descending from the same pioneer. Despite the high prevalence of both disorders in these families, no EvC individual has ever been reported with BPI. The proximity of the EVC gene to our previously reported chromosome 4p16 BPAD locus with protective alleles, coupled with detailed clinical observations that EvC and BPI do not occur in the same individuals, led us to hypothesize that the genetic defect causing EvC in the Amish confers protection from BPI. This hypothesis is supported by a significant negative association of these two disorders when contrasted with absence of disease (P=0.029, Fisher's exact test, two-sided, verified by permutation to estimate the null distribution of the test statistic). As homozygous Amish EVC mutations causing EvC dwarfism do so by disrupting sonic hedgehog (Shh) signaling, our data implicate Shh signaling in the underlying pathophysiology of BPAD. Understanding how disrupted Shh signaling protects against BPI could uncover variants in the Shh pathway that cause or increase risk for this and related mood disorders.

The M2 muscarinic receptors are essential for signaling in the heart left ventricle during restraint stress in mice.

PubMed

Tomankova, Hana; Valuskova, Paulina; Varejkova, Eva; Rotkova, Jana; Benes, Jan; Myslivecek, Jaromir

2015-01-01

We hypothesized that muscarinic receptors (MRs) in the heart have a role in stress responses and thus investigated changes in MR signaling (gene expression, number of receptors, adenylyl cyclase (AC), phospholipase C (PLC), protein kinase A and C (PKA and PKC) and nitric oxide synthase [NOS]) in the left ventricle, together with telemetric measurement of heart rate (HR) in mice (wild type [WT] and M2 knockout [KO]) during and after one (1R) or seven sessions (7R) of restraint stress (seven mice per group). Stress decreased M2 MR mRNA and cell surface MR in the left ventricle in WT mice. In KO mice, 1R, but not 7R, decreased surface MR. Similarly, AC activity was decreased in WT mice after 1R and 7R, whereas in KO mice, there was no change. PLC activity was also decreased after 1R in WT and KO mice. This is in accord with the concept that cAMP is a key player in HR regulation. No change was found with stress in NOS activity. Amount of AC and PKA protein was not changed, but was altered for PKC isoenzymes (PKCα, β, γ, η and ϵ (increased) in KO mice, and PKCι (increased) in WT mice). KO mice were more susceptible to stress as shown by inability to compensate HR during 120 min following repeated stress. The results imply that not only M2 but also M3 are involved in stress signaling and in allostasis. We conclude that for a normal stress response, the expression of M2 MR to mediate vagal responses is essential.

Do Right- and Left-Handed Monkeys Differ on Cognitive Measures?

NASA Technical Reports Server (NTRS)

Hopkins, William D.; Washburn, David A.

1994-01-01

Twelve left- and 14 right-handed monkeys were compared on 6 measures of cognitive performance (2 maze-solving tasks, matching-to-sample, delayed matching-to-sample, delayed response using spatial cues, and delayed response using form cues). The dependent variable was trials-to-training criterion for each of the 6 tasks. Significant differences were found between left- and right-handed monkeys on the 2 versions of the delayed response task. Right-handed monkeys reached criterion significantly faster on the form cue version of the task, whereas left-handed monkeys reached criterion significantly faster on delayed response for spatial position (p less than .05). The results suggest that sensitive hand preference measures of laterality can reveal differences in cognitive performance, which in turn may reflect underlying laterality in functional organization of the nervous system.

High salt solution structure of a left-handed RNA double helix

PubMed Central

Popenda, Mariusz; Milecki, Jan; Adamiak, Ryszard W.

2004-01-01

Right-handed RNA duplexes of (CG)n sequence undergo salt-induced helicity reversal, forming left-handed RNA double helices (Z-RNA). In contrast to the thoroughly studied Z-DNA, no Z-RNA structure of natural origin is known. Here we report the NMR structure of a half-turn, left-handed RNA helix (CGCGCG)2 determined in 6 M NaClO4. This is the first nucleic acid motif determined at such high salt. Sequential assignments of non-exchangeable proton resonances of the Z-form were based on the hitherto unreported NOE connectivity path [H6(n)-H5′/H5″(n)-H8(n+1)-H1′(n+1)-H6(n+2)] found for left-handed helices. Z-RNA structure shows several conformational features significantly different from Z-DNA. Intra-strand but no inter-strand base stacking was observed for both CpG and GpC steps. Helical twist angles for CpG steps have small positive values (4–7°), whereas GpC steps have large negative values (−61°). In the full-turn model of Z-RNA (12.4 bp per turn), base pairs are much closer to the helix axis than in Z-DNA, thus both the very deep, narrow minor groove with buried cytidine 2′-OH groups, and the major groove are well defined. The 2′-OH group of cytidines plays a crucial role in the Z-RNA structure and its formation; 2′-O-methylation of cytidine, but not of guanosine residues prohibits A to Z helicity reversal. PMID:15292450

SC79 protects retinal pigment epithelium cells from UV radiation via activating Akt-Nrf2 signaling

PubMed Central

Cao, Guo-fan; Cao, Cong; Jiang, Qin

2016-01-01

Excessive Ultra-violet (UV) radiation causes oxidative damages and apoptosis in retinal pigment epithelium (RPE) cells. Here we tested the potential activity of SC79, a novel small molecule activator of Akt, against the process. We showed that SC79 activated Akt in primary and established (ARPE-19 line) RPE cells. It protected RPE cells from UV damages possibly via inhibiting cell apoptosis. Akt inhibition, via an Akt specific inhibitor (MK-2206) or Akt1 shRNA silence, almost abolished SC79-induced RPE cytoprotection. Further studies showed that SC79 activated Akt-dependent NF-E2-related factor 2 (Nrf2) signaling and inhibited UV-induced oxidative stress in RPE cells. Reversely, Nrf2 shRNA knockdown or S40T mutation attenuated SC79-induced anti-UV activity. For the in vivo studies, we showed that intravitreal injection of SC79 significantly protected mouse retina from light damages. Based on these results, we suggest that SC79 protects RPE cells from UV damages possibly via activating Akt-Nrf2 signaling axis. PMID:27517753

Hyperoside protects cortical neurons from oxygen-glucose deprivation-reperfusion induced injury via nitric oxide signal pathway.

PubMed

Liu, Rui-Li; Xiong, Qiu-Ju; Shu, Qing; Wu, Wen-Ning; Cheng, Jin; Fu, Hui; Wang, Fang; Chen, Jian-Guo; Hu, Zhuang-Li

2012-08-21

Hyperoside is a flavonoid compound and widely used in clinic to relieve pain and improve cardiovascular functions. However, the effects of hyperoside on ischemic neurons and the molecular mechanisms remain unclear. Here, we used an in vitro ischemic model of oxygen-glucose deprivation followed by reperfusion (OGD-R) to investigate the protective effects of hyperoside on ischemic neuron injury and further explore the possible related mechanisms. Our results demonstrated that hyperoside protected cultured cortical neurons from OGD-R injury, it also relieved glutamate-induced neuronal injury and NMDA-induced [Ca(2+)](i) elevation. As for the mechanisms, hyperoside firstly attenuated the phosphorylation of CaMKII caused by OGD-R lesions. Meanwhile, hyperoside lessened iNOS expression induced by OGD-R via inhibition of NF-κB activation. Furthermore, ameliorating of ERK, JNK and Bcl-2 family-related apoptotic signaling pathways were also involved in the neuroprotection of hyperoside. Taken together, these studies revealed that hyperoside had protective effects on neuronal ischemia-reperfusion impairment, which was related to the regulation of nitric oxide signaling pathway. Copyright © 2012 Elsevier B.V. All rights reserved.

New Insight into the Role of Reactive Oxygen Species (ROS) in Cellular Signal-Transduction Processes.

PubMed

Russell, Eileen G; Cotter, Thomas G

2015-01-01

Reactive oxygen species (ROS) were once considered to be deleterious agents, contributing to a vast range of pathologies. But, now their protective effects are being appreciated. Both their damaging and beneficial effects are initiated when they target distinct molecules and consequently begin functioning as part of complex signal-transduction pathways. The recognition of ROS as signaling mediators has driven a wealth of research into their roles in both normal and pathophysiological states. The present review assesses the relevant recent literature to outline the current perspectives on redox-signaling mechanisms, physiological implications, and therapeutic strategies. This study highlights that a more fundamental knowledge about many aspects of redox signaling will allow better targeting of ROS, which would in turn improve prophylactic and pharmacotherapy for redox-associated diseases. Copyright © 2015 Elsevier Inc. All rights reserved.

Spectroscopic sampling of the left side of long-TE spin echoes: a free lunch?

PubMed

Mulkern, Robert V; Balasubramanian, Mukund

2018-04-01

Use of spectroscopically-acquired spin echoes typically involves Fourier transformation of the right side of the echo while largely neglecting the left side. For sufficiently long echo times, the left side may have enough spectral resolution to offer some utility. Since the acquisition of this side is "free", we deemed it worthy of attention and investigated the spectral properties and information content of this data. Theoretical expressions for left- and right-side spectra were derived assuming Lorentzian frequency distributions. For left-side spectra, three regimes were identified based upon the relative magnitudes of reversible and irreversible transverse relaxation rates, R 2 ' and R 2 , respectively. Point-resolved spectroscopy (PRESS) data from muscle, fat deposit and bone marrow were acquired at 1.5 T to test aspects of the theoretical expressions. For muscle water or methylene marrow resonances, left-side signals were substantially or moderately larger than right-side signals but were similar in magnitude for muscle choline and creatine resonances. Left- versus right-side spectral-peak amplitude ratios depend sensitively on the relative values of R 2 and R 2 ' , which can be estimated given this ratio and a right-side linewidth measurement. Left-side spectra can be used to augment signal-to-noise and to estimate spectral R 2 and R 2 ' values under some circumstances.

Activation of KGFR-Akt-mTOR-Nrf2 signaling protects human retinal pigment epithelium cells from Ultra-violet.

PubMed

Hu, Haitao; Hao, Lanxiang; Tang, Chunzhou; Zhu, Yunxi; Jiang, Qin; Yao, Jin

2018-01-15

Ultra-violet (UV) radiation causes oxidative injuries to human retinal pigment epithelium (RPE) cells. We tested the potential effect of keratinocyte growth factor (KGF) against the process. KGF receptor (KGFR) is expressed in ARPE-19 cells and primary human RPE cells. Pre-treatment with KGF inhibited UV-induced reactive oxygen species (ROS) production and RPE cell death. KGF activated nuclear-factor-E2-related factor 2 (Nrf2) signaling in RPE cells, causing Nrf2 Ser-40 phosphorylation, stabilization and nuclear translocation as well as expression of Nrf2-dependent genes (HO1, NOQ1 and GCLC). Nrf2 knockdown (by targeted shRNAs) or S40T mutation almost reversed KGF-induced RPE cell protection against UV. Further studies demonstrated that KGF activated KGFR-Akt-mTORC1 signaling to mediate downstream Nrf2 activation. KGFR shRNA or Akt-mTORC1 inhibition not only blocked KGF-induced Nrf2 Ser-40 phosphorylation and activation, but also nullified KGF-mediated RPE cell protection against UV. We conclude that KGF-KGFR activates Akt-mTORC1 downstream Nrf2 signaling to protect RPE cells from UV radiation. Copyright © 2017 Elsevier Inc. All rights reserved.

Turn-Taking, Turn-Giving, and Alzheimer's Disease.

ERIC Educational Resources Information Center

Sabat, Steven R.

1991-01-01

Analysis of a conversation with an Alzheimer's disease sufferer with word-finding problems revealed that social context, speaker characteristics, and awareness of the other speaker's perspective governed such conversational aspects of turn taking and turn giving, which allowed full development of both speakers' personas. (23 references) (CB)

Phase Retrieval from Modulus Using Homeomorphic Signal Processing and the Complex Cepstrum: An Algorithm for Lightning Protection Systems

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

Clark, G A

2004-06-08

In general, the Phase Retrieval from Modulus problem is very difficult. In this report, we solve the difficult, but somewhat more tractable case in which we constrain the solution to a minimum phase reconstruction. We exploit the real-and imaginary part sufficiency properties of the Fourier and Hilbert Transforms of causal sequences to develop an algorithm for reconstructing spectral phase given only spectral modulus. The algorithm uses homeomorphic signal processing methods with the complex cepstrum. The formal problem of interest is: Given measurements of only the modulus {vert_bar}H(k){vert_bar} (no phase) of the Discrete Fourier Transform (DFT) of a real, finite-length, stable,more » causal time domain signal h(n), compute a minimum phase reconstruction {cflx h}(n) of the signal. Then compute the phase of {cflx h}(n) using a DFT, and exploit the result as an estimate of the phase of h(n). The development of the algorithm is quite involved, but the final algorithm and its implementation are very simple. This work was motivated by a Phase Retrieval from Modulus Problem that arose in LLNL Defense Sciences Engineering Division (DSED) projects in lightning protection for buildings. The measurements are limited to modulus-only spectra from a spectrum analyzer. However, it is desired to perform system identification on the building to compute impulse responses and transfer functions that describe the amount of lightning energy that will be transferred from the outside of the building to the inside. This calculation requires knowledge of the entire signals (both modulus and phase). The algorithm and software described in this report are proposed as an approach to phase retrieval that can be used for programmatic needs. This report presents a brief tutorial description of the mathematical problem and the derivation of the phase retrieval algorithm. The efficacy of the theory is demonstrated using simulated signals that meet the assumptions of the algorithm. We see

Modulation of Rho-ROCK Signaling Pathway Protects Oligodendrocytes Against Cytokine Toxicity via PPAR-α-Dependent Mechanism

PubMed Central

Singh, Avtar K.; Singh, Inderjit

2013-01-01

We earlier documented that lovastatin (LOV)-mediated inhibition of small Rho GTPases activity protects vulnerable oligodendrocytes (OLs) in mixed glial cell cultures stimulated with Th1 cytokines and in a murine model of multiple sclerosis (MS). However, the precise mechanism of OL protection remains unclear. We here employed genetic and biochemical approaches to elucidate the underlying mechanism that protects LOV treated OLs from Th1 (tumor necrosis factor-α) and Th17 (interleukin-17) cytokines toxicity in in vitro. Cytokines enhanced the reactive oxygen species (ROS) generation and mitochondrial membrane depolarization with corresponding lowering of glutathione (reduced) level in OLs and that were reverted by LOV. In addition, the expression of ROS detoxifying enzymes (catalase and superoxide-dismutase 2) and the transactivation of peroxisome proliferators-activated receptor (PPAR)-α/-β/-γ including PPAR-γ coactivator-1α were enhanced by LOV in similarly treated OLs. Interestingly, LOV-mediated inhibition of small Rho GTPases, i.e., RhoA and cdc42, and Rho-associated kinase (ROCK) activity enhanced the levels of PPAR ligands in OLs via extracellular signal regulated kinase (1/2)/p38 mitogen-activated protein kinase/cytoplasmic phospholipase 2/cyclooxygenase-2 signaling cascade activation. Small hairpin RNA transfection-based studies established that LOV mainly enhances PPAR-α and less so of PPAR-β and PPAR-γ transactivation that enhances ROS detoxifying defense in OLs. In support of this, the observed LOV-mediated protection was lacking in PPAR-α-deficient OLs exposed to cytokines. Collectively, these data provide unprecedented evidence that LOV-mediated inhibition of the Rho–ROCK signaling pathway boosts ROS detoxifying defense in OLs via PPAR-α-dependent mechanism that has implication in neurodegenerative disorders including MS. PMID:23839981

Epithelial-specific A2B adenosine receptor signaling protects the colonic epithelial barrier during acute colitis

PubMed Central

Aherne, CM; Saeedi, B; Collins, CB; Masterson, JC; McNamee, EN; Perrenoud, L; Rapp, CR; Curtis, VF; Bayless, A; Fletcher, A; Glover, LE; Evans, CM; Jedlicka, P; Furuta, GT; de Zoeten, EF; Colgan, SP; Eltzschig, HK

2015-01-01

Central to inflammatory bowel disease (IBD) pathogenesis is loss of mucosal barrier function. Emerging evidence implicates extracellular adenosine signaling in attenuating mucosal inflammation. We hypothesized that adenosine-mediated protection from intestinal barrier dysfunction involves tissue-specific signaling through the A2B adenosine receptor (Adora2b) at the intestinal mucosal surface. To address this hypothesis, we combined pharmacologic studies and studies in mice with global or tissue-specific deletion of the Adora2b receptor. Adora2b−/− mice experienced a significantly heightened severity of colitis, associated with a more acute onset of disease and loss of intestinal epithelial barrier function. Comparison of mice with Adora2b deletion on vascular endothelial cells (Adora2bfl/flVeCadCre+) or intestinal epithelia (Adora2bfl/flVillinCre+) revealed a selective role for epithelial Adora2b signaling in attenuating colonic inflammation. In vitro studies with Adora2b knockdown in intestinal epithelial cultures or pharmacologic studies highlighted Adora2b-driven phosphorylation of vasodilator-stimulated phosphoprotein (VASP) as a specific barrier repair response. Similarly, in vivo studies in genetic mouse models or treatment studies with an Adora2b agonist (BAY 60-6583) recapitulate these findings. Taken together, our results suggest that intestinal epithelial Adora2b signaling provides protection during intestinal inflammation via enhancing mucosal barrier responses. PMID:25850656

SIRT1 and SIRT6 Signaling Pathways in Cardiovascular Disease Protection

PubMed Central

D'Onofrio, Nunzia; Servillo, Luigi

2018-01-01

Abstract Significance: Oxidative stress represents the common hallmark of pathological conditions associated with cardiovascular disease (CVD), including atherosclerosis, heart failure, hypertension, aging, diabetes, and other vascular system-related diseases. The sirtuin (SIRT) family, comprising seven proteins (SIRT1–SIRT7) sharing a highly conserved nicotinamide adenine dinucleotide (NAD+)-binding catalytic domain, attracted a great attention for the past few years as stress adaptor and epigenetic enzymes involved in the cellular events controlling aging-related disorder, cancer, and CVD. Recent Advances: Among sirtuins, SIRT1 and SIRT6 are the best characterized for their protective roles against inflammation, vascular aging, heart disease, and atherosclerotic plaque development. This latest role has been only recently unveiled for SIRT6. Of interest, in recent years, complex signaling networks controlled by SIRT1 and SIRT6 common to stress resistance, vascular aging, and CVD have emerged. Critical Issues: We provide a comprehensive overview of recent developments on the molecular signaling pathways controlled by SIRT1 and SIRT6, two post-translational modifiers proven to be valuable tools to dampen inflammation and oxidative stress at the cardiovascular level. Future Directions: A deeper understanding of the epigenetic mechanisms through which SIRT1 and SIRT6 act in the signalings responsible for onset and development CVD is a prime scientific endeavor of the upcoming years. Multiple “omic” technologies will have widespread implications in understanding such mechanisms, speeding up the achievement of selective and efficient pharmacological modulation of sirtuins for future applications in the prevention and treatment of CVD. Antioxid. Redox Signal. 28, 711–732. PMID:28661724

Left ventricular hypertrophy: virtuous intentions, malign consequences.

PubMed

Pokharel, Saraswati; Sharma, Umesh C; Pinto, Yigal M

2003-06-01

Left ventricular hypertrophy (LVH) is currently the focus of intense cardiovascular research, with the resultant rapid evolution of novel concepts relating to its exceedingly complex pathophysiology. In addition to the alterations in signal transduction and disturbances in Ca(2+) homeostasis, there are structural changes in myofilaments, disorganization of the cytoskeletal framework and increased collagen synthesis. LVH is associated with progressive left ventricular remodeling that culminates to heart failure. The modern treatment of left ventricular hypertrophy is now largely based on the hypothesis that neuroendocrine activation is important in the progression of the disease and inhibition of neurohormones is likely to have long-term benefit with regard to morbidity and mortality. Drugs specifically designed to unload the left ventricle, such as diuretics and vasodilators, appears to be less effective in reducing LV mass and improving prognosis. Thus, the evolution of treatment for LVH itself has provided much enlightenment for our understanding of the fundamental biology of the disorder.

Hydrogen gas inhalation protects against liver ischemia/reperfusion injury by activating the NF-κB signaling pathway

PubMed Central

ZHANG, CHAO-BIN; TANG, YI-CHEN; XU, XUE-JUN; GUO, SHI-XIANG; WANG, HUAI-ZHI

2015-01-01

Hydrogen has been demonstrated to function as a novel antioxidant and exert therapeutic antioxidant activity in a number of diseases. The present study was designed to investigate the effect of hydrogen inhalation on liver ischemia/reperfusion (I/R) injury in rats. The portal triad to the left lobe and the left middle lobe of the liver were completely occluded for 90 min. This was followed by reperfusion for 180 min. The rats subsequently underwent syngeneic orthotopic liver transplantation. Inhalation of various concentrations (1, 2 and 3%) of hydrogen gas and its administration for different durations (1, 3 and 6 h) immediately prior to the I/R injury allowed the optimal dose and duration of administration to be determined. Liver injury was evaluated through biochemical and histopathological examinations. The expression levels of proinflammatory cytokines, including tumor necrosis factor (TNF)-α and interleukin (IL)-6, were measured by enzyme-linked immunosorbent assay and quantitative polymerase chain reaction (qPCR). Liver nuclear factor κB (NF-κB) was detected by qPCR and western blot analysis. Inhalation of hydrogen gas at 2% concentration for 1 h significantly reduced the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, the expression of cytokines, including IL-6, TNF-α, early growth response protein 1 (Egr-1) and IL-1β, and morphological damage. In addition, the mRNA and protein expression levels of NF-κB, heme oxygenase-1 (HO-1), B-cell lymphoma 2 (Bcl-2) and zinc finger protein A20 (A20) in rats where only the donors received hydrogen were significantly increased compared with those in rats where both the donor and recipient, or only the recipient received hydrogen. The results indicate that hydrogen inhalation at 2% concentration for 1 h prior to liver transplantation protected the rats from ischemia/reperfusion injury by activation of the NF-κB signaling pathway. PMID:26136944

BDNF/TrkB signaling protects HT-29 human colon cancer cells from EGFR inhibition

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

Brunetto de Farias, Caroline; Children's Cancer Institute, 90420-140 Porto Alegre, RS; Laboratory of Neuropharmacology and Neural Tumor Biology, Department of Pharmacology, Institute for Basic Health Sciences, Federal University of Rio Grande do Sul, 90050-170 Porto Alegre, RS

2012-08-24

Highlights: Black-Right-Pointing-Pointer BDNF protected HT-29 colorectal cancer cells from the antitumor effect of cetuximab. Black-Right-Pointing-Pointer TrkB inhibition potentiated the antitumor effect of cetuximab. Black-Right-Pointing-Pointer BDNF/TrkB signaling might be involved in resistance to anti-EGFR therapy. -- Abstract: The clinical success of targeted treatment of colorectal cancer (CRC) is often limited by resistance to anti-epidermal growth factor receptor (EGFR) therapy. The neurotrophin brain-derived neurotrophic factor (BDNF) and its receptor TrkB have recently emerged as anticancer targets, and we have previously shown increased BDNF levels in CRC tumor samples. Here we report the findings from in vitro experiments suggesting that BDNF/TrkB signaling canmore » protect CRC cells from the antitumor effects of EGFR blockade. The anti-EGFR monoclonal antibody cetuximab reduced both cell proliferation and the mRNA expression of BDNF and TrkB in human HT-29 CRC cells. The inhibitory effect of cetuximab on cell proliferation and survival was counteracted by the addition of human recombinant BDNF. Finally, the Trk inhibitor K252a synergistically enhanced the effect of cetuximab on cell proliferation, and this effect was blocked by BDNF. These results provide the first evidence that increased BDNF/TrkB signaling might play a role in resistance to EGFR blockade. Moreover, it is possible that targeting TrkB could potentiate the anticancer effects of anti-EGFR therapy.« less

Vibration Sensor Monitoring of Nickel-Titanium Alloy Turning for Machinability Evaluation.

PubMed

Segreto, Tiziana; Caggiano, Alessandra; Karam, Sara; Teti, Roberto

2017-12-12

Nickel-Titanium (Ni-Ti) alloys are very difficult-to-machine materials causing notable manufacturing problems due to their unique mechanical properties, including superelasticity, high ductility, and severe strain-hardening. In this framework, the aim of this paper is to assess the machinability of Ni-Ti alloys with reference to turning processes in order to realize a reliable and robust in-process identification of machinability conditions. An on-line sensor monitoring procedure based on the acquisition of vibration signals was implemented during the experimental turning tests. The detected vibration sensorial data were processed through an advanced signal processing method in time-frequency domain based on wavelet packet transform (WPT). The extracted sensorial features were used to construct WPT pattern feature vectors to send as input to suitably configured neural networks (NNs) for cognitive pattern recognition in order to evaluate the correlation between input sensorial information and output machinability conditions.

Vibration Sensor Monitoring of Nickel-Titanium Alloy Turning for Machinability Evaluation

PubMed Central

Segreto, Tiziana; Karam, Sara; Teti, Roberto

2017-01-01

Nickel-Titanium (Ni-Ti) alloys are very difficult-to-machine materials causing notable manufacturing problems due to their unique mechanical properties, including superelasticity, high ductility, and severe strain-hardening. In this framework, the aim of this paper is to assess the machinability of Ni-Ti alloys with reference to turning processes in order to realize a reliable and robust in-process identification of machinability conditions. An on-line sensor monitoring procedure based on the acquisition of vibration signals was implemented during the experimental turning tests. The detected vibration sensorial data were processed through an advanced signal processing method in time-frequency domain based on wavelet packet transform (WPT). The extracted sensorial features were used to construct WPT pattern feature vectors to send as input to suitably configured neural networks (NNs) for cognitive pattern recognition in order to evaluate the correlation between input sensorial information and output machinability conditions. PMID:29231864

Stochastic left-right neuronal asymmetry in Caenorhabditis elegans.

PubMed

Alqadah, Amel; Hsieh, Yi-Wen; Xiong, Rui; Chuang, Chiou-Fen

2016-12-19

Left-right asymmetry in the nervous system is observed across species. Defects in left-right cerebral asymmetry are linked to several neurological diseases, but the molecular mechanisms underlying brain asymmetry in vertebrates are still not very well understood. The Caenorhabditis elegans left and right amphid wing 'C' (AWC) olfactory neurons communicate through intercellular calcium signalling in a transient embryonic gap junction neural network to specify two asymmetric subtypes, AWC OFF (default) and AWC ON (induced), in a stochastic manner. Here, we highlight the molecular mechanisms that establish and maintain stochastic AWC asymmetry. As the components of the AWC asymmetry pathway are highly conserved, insights from the model organism C. elegans may provide a window onto how brain asymmetry develops in humans.This article is part of the themed issue 'Provocative questions in left-right asymmetry'. © 2016 The Author(s).

RhNRG-1β Protects the Myocardium against Irradiation-Induced Damage via the ErbB2-ERK-SIRT1 Signaling Pathway

PubMed Central

Gu, Anxin; Jie, Yamin; Sun, Liang; Zhao, Shuping; E, Mingyan; You, Qingshan

2015-01-01

Radiation-induced heart disease (RIHD), which is a serious side effect of the radiotherapy applied for various tumors due to the inevitable irradiation of the heart, cannot be treated effectively using current clinical therapies. Here, we demonstrated that rhNRG-1β, an epidermal growth factor (EGF)-like protein, protects myocardium tissue against irradiation-induced damage and preserves cardiac function. rhNRG-1β effectively ameliorated irradiation-induced myocardial nuclear damage in both cultured adult rat-derived cardiomyocytes and rat myocardium tissue via NRG/ErbB2 signaling. By activating ErbB2, rhNRG-1β maintained mitochondrial integrity, ATP production, respiratory chain function and the Krebs cycle status in irradiated cardiomyocytes. Moreover, the protection of irradiated cardiomyocytes and myocardium tissue by rhNRG-1β was at least partly mediated by the activation of the ErbB2-ERK-SIRT1 signaling pathway. Long-term observations further showed that rhNRG-1β administered in the peri-irradiation period exerts continuous protective effects on cardiac pump function, the myocardial energy metabolism, cardiomyocyte volume and interstitial fibrosis in the rats receiving radiation via NRG/ErbB2 signaling. Our findings indicate that rhNRG-1β can protect the myocardium against irradiation-induced damage and preserve cardiac function via the ErbB2-ERK-SIRT1 signaling pathway. PMID:26332771

Targeted Knockdown of Bone Morphogenetic Protein Signaling within Neural Progenitors Protects the Brain and Improves Motor Function following Postnatal Hypoxia-Ischemia

PubMed Central

Dettman, Robert W.; Birch, Derin; Fernando, Augusta; Kessler, John A.; Dizon, Maria L.V.

2018-01-01

Hypoxic-ischemic injury (HI) to the neonatal human brain results in myelin loss that, in some children, can manifest as cerebral palsy. Previously, we had found that neuronal overexpression of the bone morphogenic protein (BMP) inhibitor noggin during development increased oligodendroglia and improved motor function in an experimental model of HI utilizing unilateral common carotid artery ligation followed by hypoxia. As BMPs are known to negatively regulate oligodendroglial fate specification of neural stem cells and alter differentiation of committed oligodendroglia, BMP signaling is likely an important mechanism leading to myelin loss. Here, we showed that BMP signaling is upregulated within oligodendroglia of the neonatal brain. We tested the hypothesis that inhibition of BMP signaling specifically within neural progenitor cells (NPCs) is sufficient to protect oligodendroglia. We conditionally deleted the BMP receptor 2 subtype (BMPR2) in NG2-expressing cells after HI. We found that BMPR2 deletion globally protects the brain as assessed by MRI and protects motor function as assessed by digital gait analysis, and that conditional deletion of BMPR2 maintains oligodendrocyte marker expression by immunofluorescence and Western blot and prevents loss of oligodendroglia. Finally, BMPR2 deletion after HI results in an increase in noncompacted myelin. Thus, our data indicate that inhibition of BMP signaling specifically in NPCs may be a tractable strategy to protect the newborn brain from HI. PMID:29324456

Physical limits of flow sensing in the left-right organizer

PubMed Central

Ferreira, Rita R; Vilfan, Andrej; Jülicher, Frank; Supatto, Willy; Vermot, Julien

2017-01-01

Fluid flows generated by motile cilia are guiding the establishment of the left-right asymmetry of the body in the vertebrate left-right organizer. Competing hypotheses have been proposed: the direction of flow is sensed either through mechanosensation, or via the detection of chemical signals transported in the flow. We investigated the physical limits of flow detection to clarify which mechanisms could be reliably used for symmetry breaking. We integrated parameters describing cilia distribution and orientation obtained in vivo in zebrafish into a multiscale physical study of flow generation and detection. Our results show that the number of immotile cilia is too small to ensure robust left and right determination by mechanosensing, given the large spatial variability of the flow. However, motile cilia could sense their own motion by a yet unknown mechanism. Finally, transport of chemical signals by the flow can provide a simple and reliable mechanism of asymmetry establishment. DOI: http://dx.doi.org/10.7554/eLife.25078.001 PMID:28613157

Magnolol protects against oxidative stress-mediated neural cell damage by modulating mitochondrial dysfunction and PI3K/Akt signaling.

PubMed

Dong, Liqun; Zhou, Shu; Yang, Xiaohua; Chen, Qianming; He, Yang; Huang, Wen

2013-07-01

Magnolol, an orally available compound from Magnolia officinalis used widely in traditional herbal medicine against a variety of neuronal diseases, possesses potent antioxidant properties and protects the brain against oxidative damage. The aim of the work is to examine the protective mechanisms of magnolol on human neuroblastoma SH-SY5Y cells against apoptosis induced by the neurotoxin acrolein, which can cause neurodegenerative disorders by inducing oxidative stress. By investigating the effect of magnolol on neural cell damage induced by the neurotoxin acrolein, we found that magnolol pretreatment significantly attenuated acrolein-induced oxidative stress through inhibiting reactive oxygen species accumulation caused by intracellular glutathione depletion and nicotinamide adenine dinucleotide phosphate oxidase activation. We next examined the signaling cascade(s) involved in magnolol-mediated antiapoptotic effects. The results showed that acrolein induced SH-SY5Y cell apoptosis by activating mitochondria/caspase and MEK/ERK signaling pathways. Our findings provide the first evidence that magnolol protects SH-SY5Y cells against acrolein-induced oxidative stress and prolongs SH-SY5Y cell survival through regulating JNK/mitochondria/caspase, PI3K/MEK/ERK, and PI3K/Akt/FoxO1 signaling pathways.

Modeling left turn queue lengths.

DOT National Transportation Integrated Search

2011-01-01

This guidebook provides methodologies and procedures for using incident data collected at Texas transportation management centers (TMCs) to perform two types of analysis - evaluation/planning analysis and predictive analysis. For the evaluation/plann...

Protective Roles of Interferon-γ in Cardiac Hypertrophy Induced by Sustained Pressure Overload.

PubMed

Kimura, Akihiko; Ishida, Yuko; Furuta, Machi; Nosaka, Mizuho; Kuninaka, Yumi; Taruya, Akira; Mukaida, Naofumi; Kondo, Toshikazu

2018-03-19

A clear understanding of the molecular mechanisms underlying hemodynamic stress-initiated cardiac hypertrophy is important for preventing heart failure. Interferon-γ (IFN-γ) has been suggested to play crucial roles in various diseases other than immunological disorders by modulating the expression of myriad genes. However, the involvement of IFN-γ in the pathogenesis of cardiac hypertrophy still remains unclear. In order to elucidate the roles of IFN-γ in pressure overload-induced cardiac pathology, we subjected Balb/c wild-type (WT) or IFN-γ-deficient ( Ifng -/- ) mice to transverse aortic constriction (TAC). Three weeks after TAC, Ifng -/- mice developed more severe cardiac hypertrophy, fibrosis, and dysfunction than WT mice. Bone marrow-derived immune cells including macrophages were a source of IFN-γ in hearts after TAC. The activation of PI3K/Akt signaling, a key signaling pathway in compensatory hypertrophy, was detected 3 days after TAC in the left ventricles of WT mice and was markedly attenuated in Ifng -/- mice. The administration of a neutralizing anti-IFN-γ antibody abrogated PI3K/Akt signal activation in WT mice during compensatory hypertrophy, while that of IFN-γ activated PI3K/Akt signaling in Ifng -/- mice. TAC also induced the phosphorylation of Stat5, but not Stat1 in the left ventricles of WT mice 3 days after TAC. Furthermore, IFN-γ induced Stat5 and Akt phosphorylation in rat cardiomyocytes cultured under stretch conditions. A Stat5 inhibitor significantly suppressed PI3K/Akt signaling activation in the left ventricles of WT mice, and aggravated pressure overload-induced cardiac hypertrophy. The IFN-γ/Stat5 axis may be protective against persistent pressure overload-induced cardiac hypertrophy by activating the PI3K/Akt pathway. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Wheelchair pushing and turning: lumbar spine and shoulder loads and recommended limits.

PubMed

Weston, Eric B; Khan, Safdar N; Marras, William S

2017-12-01

The objective of this study was to determine how simulated manual wheelchair pushing influences biomechanical loading to the lumbar spine and shoulders. Sixty-two subjects performed simulated wheelchair pushing and turning in a laboratory. An electromyography-assisted biomechanical model was used to estimate spinal loads. Moments at the shoulder joint, external hand forces and net turning torque were also assessed. Multiple linear regression techniques were employed to develop biomechanically based wheelchair pushing guidelines relating resultant hand force or net torque to spinal load. Male subjects experienced significantly greater spinal loading (p < 0.01), and spine loads were also increased for wheelchair turning compared to straight wheelchair pushing (p < 0.001). Biomechanically determined maximum acceptable resultant hand forces were 17-18% lower than psychophysically determined limits. We conclude that manual wheelchair pushing and turning can pose biomechanical risk to the lumbar spine and shoulders. Psychophysically determined maximum acceptable push forces do not appear to be protective enough of this biomechanical risk. Practitioner Summary: This laboratory study investigated biomechanical risk to the low back and shoulders during simulated wheelchair pushing. Manual wheelchair pushing posed biomechanical risk to the lumbar spine (in compression and A/P shear) and to the shoulders. Biomechanically determined wheelchair pushing thresholds are presented and are more protective than the closest psychophysically determined equivalents.

Constitutive overexpression of Norrin activates Wnt/β-catenin and endothelin-2 signaling to protect photoreceptors from light damage.

PubMed

Braunger, Barbara M; Ohlmann, Andreas; Koch, Marcus; Tanimoto, Naoyuki; Volz, Cornelia; Yang, Ying; Bösl, Michael R; Cvekl, Ales; Jägle, Herbert; Seeliger, Mathias W; Tamm, Ernst R

2013-02-01

Norrin is a retinal signaling molecule which is expressed in Müller glia and binds to Frizzled-4 to activate canonical Wnt/β-catenin signaling. Norrin is part of an essential signaling system that controls the formation of retinal capillaries during development. To evaluate neuroprotective properties of Norrin independently from its function during retinal angiogenesis, we generated transgenic mice (Rpe65-Norrin) that constitutively express Norrin in the retinal pigmented epithelium. Substantial amounts of Norrin were secreted into the outer retina, which triggered retinal Wnt/β-catenin signaling in conjunction with an increase in the expression of endothelin-2 (EDN2), endothelin receptor B (EDNRB), and glial fibrillary acidic protein (GFAP). Photoreceptors of Norrin-overexpressing mice were significantly less vulnerable to light-induced damage compared to their wild-type littermates. Following light damage, we observed less apoptotic death of photoreceptors and a better retinal function than in controls. The protective effects were abolished if either Wnt/β-catenin or EDN2 signaling was blocked by intravitreal injection of Dickkopf-1 or BQ788, respectively. Light-damaged retinae from transgenic mice contained higher amounts of brain-derived neurotrophic factor (BDNF) and pAkt than those of wild-type littermates. We conclude that constitutive overexpression of Norrin protects photoreceptors from light damage, an effect that is mediated by Wnt/β-catenin and EDN2 signaling and involves neurotrophic activities of BDNF. The findings suggest that Norrin and its associated signaling pathways have strong potentials to attenuate photoreceptor death following injury. Copyright © 2012 Elsevier Inc. All rights reserved.

Carbon Monoxide Protects against Hepatic Ischemia/Reperfusion Injury via ROS-Dependent Akt Signaling and Inhibition of Glycogen Synthase Kinase 3β

PubMed Central

Kim, Hyo Jeong; Joe, Yeonsoo; Kong, Jin Sun; Jeong, Sun-Oh; Cho, Gyeong Jae; Ryter, Stefan W.

2013-01-01

Carbon monoxide (CO) may exert important roles in physiological and pathophysiological states through the regulation of cellular signaling pathways. CO can protect organ tissues from ischemia/reperfusion (I/R) injury by modulating intracellular redox status and by inhibiting inflammatory, apoptotic, and proliferative responses. However, the cellular mechanisms underlying the protective effects of CO in organ I/R injury remain incompletely understood. In this study, a murine model of hepatic warm I/R injury was employed to assess the role of glycogen synthase kinase-3 (GSK3) and phosphatidylinositol 3-kinase (PI3K)-dependent signaling pathways in the protective effects of CO against inflammation and injury. Inhibition of GSK3 through the PI3K/Akt pathway played a crucial role in CO-mediated protection. CO treatment increased the phosphorylation of Akt and GSK3-beta (GSK3β) in the liver after I/R injury. Furthermore, administration of LY294002, an inhibitor of PI3K, compromised the protective effect of CO and decreased the level of phospho-GSK3β after I/R injury. These results suggest that CO protects against liver damage by maintaining GSK3β phosphorylation, which may be mediated by the PI3K/Akt signaling pathway. Our study provides additional support for the therapeutic potential of CO in organ injury and identifies GSK3β as a therapeutic target for CO in the amelioration of hepatic injury. PMID:24454979

Carbon monoxide protects against hepatic ischemia/reperfusion injury via ROS-dependent Akt signaling and inhibition of glycogen synthase kinase 3β.

PubMed

Kim, Hyo Jeong; Joe, Yeonsoo; Kong, Jin Sun; Jeong, Sun-Oh; Cho, Gyeong Jae; Ryter, Stefan W; Chung, Hun Taeg

2013-01-01

Carbon monoxide (CO) may exert important roles in physiological and pathophysiological states through the regulation of cellular signaling pathways. CO can protect organ tissues from ischemia/reperfusion (I/R) injury by modulating intracellular redox status and by inhibiting inflammatory, apoptotic, and proliferative responses. However, the cellular mechanisms underlying the protective effects of CO in organ I/R injury remain incompletely understood. In this study, a murine model of hepatic warm I/R injury was employed to assess the role of glycogen synthase kinase-3 (GSK3) and phosphatidylinositol 3-kinase (PI3K)-dependent signaling pathways in the protective effects of CO against inflammation and injury. Inhibition of GSK3 through the PI3K/Akt pathway played a crucial role in CO-mediated protection. CO treatment increased the phosphorylation of Akt and GSK3-beta (GSK3β) in the liver after I/R injury. Furthermore, administration of LY294002, an inhibitor of PI3K, compromised the protective effect of CO and decreased the level of phospho-GSK3β after I/R injury. These results suggest that CO protects against liver damage by maintaining GSK3β phosphorylation, which may be mediated by the PI3K/Akt signaling pathway. Our study provides additional support for the therapeutic potential of CO in organ injury and identifies GSK3β as a therapeutic target for CO in the amelioration of hepatic injury.

NEU3 Sialidase Is Activated under Hypoxia and Protects Skeletal Muscle Cells from Apoptosis through the Activation of the Epidermal Growth Factor Receptor Signaling Pathway and the Hypoxia-inducible Factor (HIF)-1α

PubMed Central

Scaringi, Raffaella; Piccoli, Marco; Papini, Nadia; Cirillo, Federica; Conforti, Erika; Bergante, Sonia; Tringali, Cristina; Garatti, Andrea; Gelfi, Cecilia; Venerando, Bruno; Menicanti, Lorenzo; Tettamanti, Guido; Anastasia, Luigi

2013-01-01

NEU3 sialidase, a key enzyme in ganglioside metabolism, is activated under hypoxic conditions in cultured skeletal muscle cells (C2C12). NEU3 up-regulation stimulates the EGF receptor signaling pathway, which in turn activates the hypoxia-inducible factor (HIF-1α), resulting in a final increase of cell survival and proliferation. In the same cells, stable overexpression of sialidase NEU3 significantly enhances cell resistance to hypoxia, whereas stable silencing of the enzyme renders cells more susceptible to apoptosis. These data support the working hypothesis of a physiological role played by NEU3 sialidase in protecting cells from hypoxic stress and may suggest new directions in the development of therapeutic strategies against ischemic diseases, particularly of the cerebro-cardiovascular system. PMID:23209287

NEU3 sialidase is activated under hypoxia and protects skeletal muscle cells from apoptosis through the activation of the epidermal growth factor receptor signaling pathway and the hypoxia-inducible factor (HIF)-1α.

PubMed

Scaringi, Raffaella; Piccoli, Marco; Papini, Nadia; Cirillo, Federica; Conforti, Erika; Bergante, Sonia; Tringali, Cristina; Garatti, Andrea; Gelfi, Cecilia; Venerando, Bruno; Menicanti, Lorenzo; Tettamanti, Guido; Anastasia, Luigi

2013-02-01

NEU3 sialidase, a key enzyme in ganglioside metabolism, is activated under hypoxic conditions in cultured skeletal muscle cells (C2C12). NEU3 up-regulation stimulates the EGF receptor signaling pathway, which in turn activates the hypoxia-inducible factor (HIF-1α), resulting in a final increase of cell survival and proliferation. In the same cells, stable overexpression of sialidase NEU3 significantly enhances cell resistance to hypoxia, whereas stable silencing of the enzyme renders cells more susceptible to apoptosis. These data support the working hypothesis of a physiological role played by NEU3 sialidase in protecting cells from hypoxic stress and may suggest new directions in the development of therapeutic strategies against ischemic diseases, particularly of the cerebro-cardiovascular system.

Optical spectroscopic elucidation of beta-turns in disulfide bridged cyclic tetrapeptides.

PubMed

Borics, Attila; Murphy, Richard F; Lovas, Sándor

2007-01-01

Vibrational circular dichroism (VCD) spectroscopic features of type II beta-turns were characterized previously, but, criteria for differentiation between beta-turn types had not been established yet. Model tetrapeptides, cyclized through a disulfide bridge, were designed on the basis of previous experimental results and the observed incidence of amino acid residues in the i + 1 and i + 2 positions in beta-turns, to determine the features of VCD spectra of type I and II beta-turns. The results were correlated with electronic circular dichroism (ECD) spectra and VCD spectra calculated from conformational data obtained by molecular dynamics (MD) simulations. All cyclic tetrapeptides yielded VCD signals with a higher frequency negative and a lower frequency positive couplet with negative lobes overlapping. MD simulations confirmed the conformational homogeneity of these peptides in solution. Comparison with ECD spectroscopy, MD, and quantum chemical calculation results suggested that the low frequency component of VCD spectra originating from the tertiary amide vibrations could be used to distinguish between types of beta-turn structures. On the basis of this observation, VCD spectroscopic features of type II and VIII beta-turns and ECD spectroscopic properties of a type VIII beta-turn were suggested. The need for independent experimental as well as theoretical investigations to obtain decisive conformational information was recognized. Copyright 2006 Wiley Periodicals, Inc.

Removal of single point diamond-turning marks by abrasive jet polishing.

PubMed

Li, Z Z; Wang, J M; Peng, X Q; Ho, L T; Yin, Z Q; Li, S Y; Cheung, C F

2011-06-01

Single point diamond turning (SPDT) is highly controllable and versatile in producing axially symmetric forms, non-axially-symmetric forms, microstructured surfaces, and free forms. However, the fine SPDT marks left in the surface limit its performance, and they are difficult to reduce or eliminate. It is unpractical for traditional methods to remove the fine marks without destroying their forms, especially for the aspheres and free forms. This paper introduces abrasive jet polishing (AJP) for the posttreatment of diamond-turned surfaces to remove the periodic microstructures. Samples of diamond-turned electroless nickel plated plano mirror were used in the experiments. One sample with an original surface roughness of more than 400 nm decreased to 4 nm after two iterations abrasive jet polishing; the surface roughness of another sample went from 3.7 nm to 1.4 nm after polishing. The periodic signatures on both of the samples were removed entirely after polishing. Contrastive experimental research was carried out on electroless nickel mirror with magnetorheological finishing, computer controlled optical surfacing, and AJP. The experimental results indicate that AJP is more appropriate in removing the periodic SPDT marks. Also, a figure maintaining experiment was carried out with the AJP process; the uniform polishing process shows that the AJP process can remove the periodic turning marks without destroying the original form.

Monitoring of Surface Roughness in Aluminium Turning Process

NASA Astrophysics Data System (ADS)

Chaijareenont, Atitaya; Tangjitsitcharoen, Somkiat

2018-01-01

As the turning process is one of the most necessary process. The surface roughness has been considered for the quality of workpiece. There are many factors which affect the surface roughness. Hence, the objective of this research is to monitor the relation between the surface roughness and the cutting forces in aluminium turning process with a wide range of cutting conditions. The coated carbide tool and aluminium alloy (Al 6063) are used for this experiment. The cutting parameters are investigated to analyze the effects of them on the surface roughness which are the cutting speed, the feed rate, the tool nose radius and the depth of cut. In the case of this research, the dynamometer is installed in the turret of CNC turning machine to generate a signal while turning. The relation between dynamic cutting forces and the surface roughness profile is examined by applying the Fast Fourier Transform (FFT). The experimentally obtained results showed that the cutting force depends on the cutting condition. The surface roughness can be improved when increasing the cutting speed and the tool nose radius in contrast to the feed rate and the depth of cut. The relation between the cutting parameters and the surface roughness can be explained by the in-process cutting forces. It is understood that the in-process cutting forces are able to predict the surface roughness in the further research.

[Selective left mainstem bronchial intubation in the neonatal intensive care unit].

PubMed

Ho, Anthony M H; Flavin, Michael P; Fleming, Melinda L; Mizubuti, Glenio Bitencourt

Selective neonatal left mainstem bronchial intubation to treat right lung disease is typically achieved with elaborate maneuvers, instrumentation and devices. This is often attributed to bronchial geometry which favors right mainstem entry of an endotracheal tube deliberately advanced beyond the carina. A neonate with severe bullous emphysema affecting the right lung required urgent non-ventilation of that lung. We achieved left mainstem bronchial intubation by turning the endotracheal tube 180° such that the Murphy's eye faced the left instead of the right, and simulated a left-handed intubation by slightly orientating the endotracheal tube such that its concavity faced the left instead of the right as in a conventional right-handed intubation. Urgent intubation of the left mainstem bronchus with an endotracheal tube can be easily achieved by recognizing that it is the position of the endotracheal tube tip and the direction of its concavity that are the chief determinants of which bronchus an endotracheal tube goes when advanced. This is important in critically ill neonates as the margin of safety and time window are small, and the absence of double-lumen tubes. Use of fiberoptic bronchoscope and blockers should be reserved as backup plans. Copyright © 2017 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

Autophagy protects gastric mucosal epithelial cells from ethanol-induced oxidative damage via mTOR signaling pathway

PubMed Central

Chang, Weilong; Bai, Jie; Tian, Shaobo; Ma, Muyuan; Li, Wei; Yin, Yuping; Deng, Rui; Cui, Jinyuan; Li, Jinjin; Wang, Guobin; Tao, Kaixiong

2017-01-01

Alcohol abuse is an important cause of gastric mucosal epithelial cell injury and gastric ulcers. A number of studies have demonstrated that autophagy, an evolutionarily conserved cellular mechanism, has a protective effect on cell survival. However, it is not known whether autophagy can protect gastric mucosal epithelial cells against the toxic effects of ethanol. In the present study, gastric mucosal epithelial cells (GES-1 cells) and Wistar rats were treated with ethanol to detect the adaptive response of autophagy. Our results demonstrated that ethanol exposure induced gastric mucosal epithelial cell damage, which was accompanied by the downregulation of mTOR signaling pathway and activation of autophagy. Suppression of autophagy with pharmacological agents resulted in a significant increase of GES-1 cell apoptosis and gastric mucosa injury, suggesting that autophagy could protect cells from ethanol toxicity. Furthermore, we evaluated the cellular oxidative stress response following ethanol treatment and found that autophagy induced by ethanol inhibited generation of reactive oxygen species and degradation of antioxidant and lipid peroxidation. In conclusion, these findings provide evidence that ethanol can activate autophagy via downregulation of the mTOR signaling pathway, serving as an adaptive mechanism to ameliorate oxidative damage induced by ethanol in gastric mucosal epithelial cells. Therefore, modifying autophagy may provide a therapeutic strategy against alcoholic gastric mucosa injury. Impact statement The effect and mechanism of autophagy on ethanol-induced cell damage remain controversial. In this manuscript, we report the results of our study demonstrating that autophagy can protect gastric mucosal epithelial cells against ethanol toxicity in vitro and in vivo. We have shown that ethanol can activate autophagy via downregulation of the mTOR signaling pathway, serving as an adaptive mechanism to ameliorate ethanol-induced oxidative damage in

Safety evaluation of driver cognitive failures and driving errors on right-turn filtering movement at signalized road intersections based on Fuzzy Cellular Automata (FCA) model.

PubMed

Chai, Chen; Wong, Yiik Diew; Wang, Xuesong

2017-07-01

This paper proposes a simulation-based approach to estimate safety impact of driver cognitive failures and driving errors. Fuzzy Logic, which involves linguistic terms and uncertainty, is incorporated with Cellular Automata model to simulate decision-making process of right-turn filtering movement at signalized intersections. Simulation experiments are conducted to estimate the relationships between cognitive failures and driving errors with safety performance. Simulation results show Different types of cognitive failures are found to have varied relationship with driving errors and safety performance. For right-turn filtering movement, cognitive failures are more likely to result in driving errors with denser conflicting traffic stream. Moreover, different driving errors are found to have different safety impacts. The study serves to provide a novel approach to linguistically assess cognitions and replicate decision-making procedures of the individual driver. Compare to crash analysis, the proposed FCA model allows quantitative estimation of particular cognitive failures, and the impact of cognitions on driving errors and safety performance. Copyright © 2017 Elsevier Ltd. All rights reserved.

Turning assistive machines into assistive robots

NASA Astrophysics Data System (ADS)

Argall, Brenna D.

2015-01-01

For decades, the potential for automation in particular, in the form of smart wheelchairs to aid those with motor, or cognitive, impairments has been recognized. It is a paradox that often the more severe a person's motor impairment, the more challenging it is for them to operate the very assistive machines which might enhance their quality of life. A primary aim of my lab is to address this confound by incorporating robotics autonomy and intelligence into assistive machines turning the machine into a kind of robot, and offloading some of the control burden from the user. Robots already synthetically sense, act in and reason about the world, and these technologies can be leveraged to help bridge the gap left by sensory, motor or cognitive impairments in the users of assistive machines. This paper overviews some of the ongoing projects in my lab, which strives to advance human ability through robotics autonomy.

Interference of silibinin with IGF-1R signalling pathways protects human epidermoid carcinoma A431 cells from UVB-induced apoptosis

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

Liu, Weiwei; Otkur, Wuxiyar; Li, Lingzhi

Highlights: ► Silibinin protects A431 cells from UVB irradiation-induced apoptosis. ► Up-regulation of the IGF-1R-JNK/ERK pathways by UVB induces cell apoptosis. ► Silibinin inhibits IGF-1R pathways to repress caspase-8-mediated apoptosis. -- Abstract: Ultraviolet B (UVB) from sunlight is a major cause of cutaneous lesion. Silibinin, a traditional hepatic protectant, elicits protective effects against UVB-induced cellular damage. In A431 cells, the insulin-like growth factor-1 receptor (IGF-1R) was markedly up-regulated by UVB irradiation. The activation of the IGF-1R signalling pathways contributed to apoptosis of the cells rather than rescuing the cells from death. Up-regulated IGF-1R stimulated downstream mitogen-activated protein kinases (MAPKs), suchmore » as c-Jun N-terminal kinases (JNK) and extracellular signal-regulated protein kinases 1/2 (ERK1/2). The subsequent activation of caspase-8 and caspase-3 led to apoptosis. The activation of IGF-1R signalling pathways is the cause of A431 cell death. The pharmacological inhibitors and the small interfering RNA (siRNA) targeting IGF-1R suppressed the downstream activation of JNK/ERK-caspases to help the survival of the UVB-irradiated A431 cells. Indeed, silibinin treatment suppressed the IGF-1R-JNK/ERK pathways and thus protected the cells from UVB-induced apoptosis.« less

Turning the School Around: The Transformation of a Secondary School from Underperforming to Highly Achieving

ERIC Educational Resources Information Center

Branch, Cynthia Monroe

2013-01-01

The No Child Left Behind Act of 2001 put a focus on each child in a school being proficient. Since 1957 when Sputnik was launched, the United States has been attempting to improve its schools. The existing literature has a gap as to how to turn around an underperforming school in a fairly short period of time. A qualitative case study methodology…

Numerical approximation of the electromechanical coupling in the left ventricle with inclusion of the Purkinje network.

PubMed

Landajuela, Mikel; Vergara, Christian; Gerbi, Antonello; Dedé, Luca; Formaggia, Luca; Quarteroni, Alfio

2018-03-25

In this work, we consider the numerical approximation of the electromechanical coupling in the left ventricle with inclusion of the Purkinje network. The mathematical model couples the 3D elastodynamics and bidomain equations for the electrophysiology in the myocardium with the 1D monodomain equation in the Purkinje network. For the numerical solution of the coupled problem, we consider a fixed-point iterative algorithm that enables a partitioned solution of the myocardium and Purkinje network problems. Different levels of myocardium-Purkinje network splitting are considered and analyzed. The results are compared with those obtained using standard strategies proposed in the literature to trigger the electrical activation. Finally, we present a numerical study that, although performed in an idealized computational domain, features all the physiological issues that characterize a heartbeat simulation, including the initiation of the signal in the Purkinje network and the systolic and diastolic phases. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Advanced insulated gate bipolar transistor gate drive

DOEpatents

Short, James Evans [Monongahela, PA; West, Shawn Michael [West Mifflin, PA; Fabean, Robert J [Donora, PA

2009-08-04

A gate drive for an insulated gate bipolar transistor (IGBT) includes a control and protection module coupled to a collector terminal of the IGBT, an optical communications module coupled to the control and protection module, a power supply module coupled to the control and protection module and an output power stage module with inputs coupled to the power supply module and the control and protection module, and outputs coupled to a gate terminal and an emitter terminal of the IGBT. The optical communications module is configured to send control signals to the control and protection module. The power supply module is configured to distribute inputted power to the control and protection module. The control and protection module outputs on/off, soft turn-off and/or soft turn-on signals to the output power stage module, which, in turn, supplies a current based on the signal(s) from the control and protection module for charging or discharging an input capacitance of the IGBT.

Complete filter-based cerebral embolic protection with transcatheter aortic valve replacement.

PubMed

Van Gils, Lennart; Kroon, Herbert; Daemen, Joost; Ren, Claire; Maugenest, Anne-Marie; Schipper, Marguerite; De Jaegere, Peter P; Van Mieghem, Nicolas M

2018-03-01

To evaluate the value of left vertebral artery filter protection in addition to the current filter-based embolic protection technology to achieve complete cerebral protection during TAVR. The occurrence of cerebrovascular events after transcatheter aortic valve replacement (TAVR) has fueled concern for its potential application in younger patients with longer life expectancy. Transcatheter cerebral embolic protection (TCEP) devices may limit periprocedural cerebrovascular events by preventing macro and micro-embolization to the brain. Conventional filter-based TCEP devices cover three extracranial contributories to the brain, yet leave the left vertebral artery unprotected. Patients underwent TAVR with complete TCEP. A dual-filter system was deployed in the brachiocephalic trunk and left common carotid artery with an additional single filter in the left vertebral artery. After TAVR all filters were retrieved and sent for histopathological evaluation by an experienced pathologist. Eleven patients received a dual-filter system and nine of them received an additional left vertebral filter. In the remaining two patients, the left vertebral filter could not be deployed. No periprocedural strokes occurred. We found debris in all filters, consisting of thrombus, tissue derived debris, and foreign body material. The left vertebral filter contained debris in an equal amount of patients as the Sentinel filters. The size of the captured particles was similar between all filters. The left vertebral artery is an important entry route for embolic material to the brain during TAVR. Selective filter protection of the left vertebral artery revealed embolic debris in all patients. The clinical value of complete filter-based TCEP during TAVR warrants further research. © 2017 Wiley Periodicals, Inc.

Protected area management

USGS Publications Warehouse

Fagre, Daniel B.; Prato, Tony; Wang, Yeqiao

2014-01-01

Designated protected areas are diverse in scope and purpose and have expanded from Yellowstone National Park in the United States, the world’s first national park, to 157,897 parks and protected areas distributed globally. Most are publicly owned and serve multiple needs that reflect regional or national cultures. With ever-increasing threats to the integrity of protected areas, managers are turning to flexible management practices such as scenario planning and adaptive management.

Clusterin protects H9c2 cardiomyocytes from oxidative stress-induced apoptosis via Akt/GSK-3β signaling pathway

PubMed Central

Jun, Hyoung-Oh; Kim, Dong-hun; Lee, Sae-Won; Lee, Hye Shin; Seo, Ji Hae; Kim, Jeong Hun; Kim, Jin Hyoung; Yu, Young Suk; Min, Bon Hong

2011-01-01

Clusterin is a secretory glycoprotein, which is highly up-regulated in a variety of normal and injury tissues undergoing apoptosis including infarct region of the myocardium. Here, we report that clusterin protects H9c2 cardiomyocytes from H2O2-induced apoptosis by triggering the activation of Akt and GSK-3β. Treatment with H2O2 induces apoptosis of H9c2 cells by promoting caspase cleavage and cytochrome c release from mitochondria. However, co-treatment with clusterin reverses the induction of apoptotic signaling by H2O2, thereby recovers cell viability. The protective effect of clusterin on H2O2-induced apoptosis is impaired by PI3K inhibitor LY294002, which effectively suppresses clusterin-induced activation of Akt and GSK-3β. In addition, the protective effect of clusterin is independednt on its receptor megalin, because inhibition of megalin has no effect on clusturin-mediated Akt/GSK-3β phosphoylation and H9c2 cell viability. Collectively, these results suggest that clusterin has a role protecting cardiomyocytes from oxidative stress and the Akt/GSK-3β signaling mediates anti-apoptotic effect of clusterin. PMID:21270507

Elective minimally invasive coronary artery bypass: Shunt or tournique occlusion? Assessment of a protective role of perioperative left anterior descending shunting on myocardial damage. A prospective randomized study

PubMed Central

2012-01-01

Background To determine impact of intraluminal-left anterior descending shunt to prevent myocardial damage in minimally invasive coronary artery bypass. Methods 38 patients were randomly assigned to external tournique occlusion (n = 19) or intraluminal-left anterior descending shunt group (n = 19). Blood samples for cardiac troponin T were collected at 30 minutes prior to, 6 and 24 hours after surgery. Results One patient in external tournique occlusion and two patients in intraluminal-left anterior descending shunt group were excluded from futher analysis due to preoperative cardiac troponin T level above the 99th-percentile. Postoperatively, each six patients in external tournique occlusion (33.3%) and intraluminal-left anterior descending shunt (35.3%) group were above the 99th-percentile. Two patients from each group (external tournique occlusion group 11.1% vs. intraluminal-left anterior descending shunt group 11.8%) had peak values above 10-% coeficient of variation cutoff (p = 1). There were no significant differences in between both groups at all studied timepoints. Conclusion There was no protective effect of intraluminal shunting on myocardial damage compared to short-term tournique occlusion. It is upon the surgeon's discretion which method may preferrably be used to achieve a bloodless field in grafting of the non-occluded left anterior descending in minimally invasive coronary artery bypass. PMID:22809563

Left-right symmetry and the charged Higgs bosons at the LHC

NASA Astrophysics Data System (ADS)

Bambhaniya, G.; Chakrabortty, J.; Gluza, J.; Kordiaczynska, M.; Szafron, R.

2014-05-01

The charged Higgs boson sector of the Minimal Manifest Left-Right Symmetric model (MLRSM) is investigated in the context of LHC discovery search for new physics beyond Standard Model. We discuss and summarise the main processes within MLRSM where heavy charged Higgs bosons can be produced at the LHC. We explore the scenarios where the amplified signals due to relatively light charged scalars dominate against heavy neutral Z 2 and charged gauge W 2 as well as heavy neutral Higgs bosons signals which are dumped due to large vacuum expectation value v R of the right-handed scalar triplet. Consistency with FCNC effects implies masses of two neutral Higgs bosons to be at least of 10 TeV order, which in turn implies that in MLRSM only three of four charged Higgs bosons, namely and ,and can be simultaneously light. In particular, production processes with one and two doubly charged Higgs bosons are considered. We further incorporate the decays of those scalars leading to multi lepton signals at the LHC. Branching ratios for heavy neutrino N R , W 2 and Z 2 decay into charged Higgs bosons are calculated. These effects are substantial enough and cannot be neglected. The tri- and four-lepton final states for different benchmark points are analysed. Kinematic cuts are chosen in order to strength the leptonic signals and decrease the Standard Model (SM) background. The results are presented using di-lepton invariant mass and lepton-lepton separation distributions for the same sign (SSDL) and opposite sign (OSDL) di-leptons as well as the charge asymmetry are also discussed. We have found that for considered MLRSM processes tri-lepton and four-lepton signals are most important for their detection when compared to the SM background. Both of the signals can be detected at 14 TeV collisions at the LHC with integrated luminosity at the level of 300 fb-1 with doubly charged Higgs bosons up to approximately 600 GeV. Finally, possible extra contribution of the charged MLRSM scalar

The performance of the standard rate turn (SRT) by student naval helicopter pilots.

PubMed

Chapman, F; Temme, L A; Still, D L

2001-04-01

During flight training, student naval helicopter pilots learn the use of flight instruments through a prescribed series of simulator training events. The training simulator is a 6-degrees-of-freedom, motion-based, high-fidelity instrument trainer. From the final basic instrument simulator flights of student pilots, we selected for evaluation and analysis their performance of the Standard Rate Turn (SRT), a routine flight maneuver. The performance of the SRT was scored with air speed, altitude and heading average error from target values and standard deviations. These average errors and standard deviations were used in a Multiple Analysis of Variance (MANOVA) to evaluate the effects of three independent variables: 1) direction of turn (left vs. right), 2) degree of turn (180 vs. 360 degrees); and 3) segment of turn (roll-in, first 30 s, last 30 s, and roll-out of turn). Only the main effects of the three independent variables were significant; there were no significant interactions. This result greatly reduces the number of different conditions that should be scored separately for the evaluation of SRT performance. The results also showed that the magnitude of the heading and altitude errors at the beginning of the SRT correlated with the magnitude of the heading and altitude errors throughout the turn. This result suggests that for the turn to be well executed, it is important for it to begin with little error in these two response parameters. The observations reported here should be considered when establishing SRT performance norms and comparing student scores. Furthermore, it seems easier for pilots to maintain good performance than to correct poor performance.

Functional MRI of facial emotion processing in left temporal lobe epilepsy.

PubMed

Szaflarski, Jerzy P; Allendorfer, Jane B; Heyse, Heidi; Mendoza, Lucy; Szaflarski, Basia A; Cohen, Nancy

2014-03-01

Temporal lobe epilepsy (TLE) may negatively affect the ability to recognize emotions. This study aimed to determine the cortical correlates of facial emotion processing (happy, sad, fearful, and neutral) in patients with well-characterized left TLE (LTLE) and to examine the effect of seizure control on emotion processing. We enrolled 34 consecutive patients with LTLE and 30 matched healthy control (HC) subjects. Participants underwent functional MRI (fMRI) with an event-related facial emotion recognition task. The seizures of seventeen patients were controlled (no seizure in at least 3months; LTLE-sz), and 17 continued to experience frequent seizures (LTLE+sz). Mood was assessed with the Beck Depression Inventory (BDI) and the Profile of Mood States (POMS). There were no differences in demographic characteristics and measures of mood between HC subjects and patients with LTLE. In patients with LTLE, fMRI showed decreased blood oxygenation level dependent (BOLD) signal in the hippocampus/parahippocampus and cerebellum in processing of happy faces and increased BOLD signal in occipital regions in response to fearful faces. Comparison of groups with LTLE+sz and LTLE-sz showed worse BDI and POMS scores in LTLE+sz (all p<0.05) except for POMS tension/anxiety (p=0.067). Functional MRI revealed increased BOLD signal in patients with LTLE+sz in the left precuneus and left parahippocampus for "fearful" faces and in the left periarcheocortex for "neutral" faces. There was a correlation between the fMRI and Total Mood Disturbance in the left precuneus in LTLE-sz (p=0.019) and in LTLE+sz (p=0.018). Overall, LTLE appears to have a relatively minor effect on the cortical underpinnings of facial emotion processing, while the effect of seizure state (controlled vs. not controlled) is more pronounced, indicating a significant relationship between seizure control and emotion processing. Copyright © 2014 Elsevier Inc. All rights reserved.

A Respiratory Marker Derived From Left Vagus Nerve Signals Recorded With Implantable Cuff Electrodes.

PubMed

Sevcencu, Cristian; Nielsen, Thomas N; Kjaergaard, Benedict; Struijk, Johannes J

2018-04-01

Left vagus nerve (LVN) stimulation (LVNS) has been tested for lowering the blood pressure (BP) in patients with resistant hypertension (RH). Whereas, closed-loop LVNS (CL-LVNS) driven by a BP marker may be superior to open-loop LVNS, there are situations (e.g., exercising) when hypertension is normal. Therefore, an ideal anti-RH CL-LVNS system requires a variable to avoid stimulation in such conditions, for example, a respiratory marker ideally extracted from the LVN. As the LVN conducts respiratory signals, this study aimed to investigate if such signals can be recorded using implantable means and if a marker to monitor respiration could be derived from such recordings. The experiments were performed in 14 anesthetized pigs. Five pigs were subjected to changes of the respiratory frequency and nine to changes of the respiratory volume. The LVN electroneurogram (VENG) was recorded using two cuff electrodes and the respiratory cycles (RC) using a pressure transducer. To separate the afferent and efferent VENGs, vagotomy was performed between the cuffs in the first group of pigs. The VENG was squared to derive respiration-related neural profiles (RnPs) and their correlation with the RCs was investigated in regard to timing and magnitude parameters derived from the two waveforms. The RnPs were morphologically similar with the RCs and the average RnPs represented accurate copies of the average RCs. Consequently, the lung inflation/deflation RC and RnP components had the same duration, the respiratory frequency changes affected in the same way both waveforms and the RnP amplitude increased linearly with the lung inflation in all tested pigs (R 2 values between 0.85 and 0.99). The RnPs comprise information regarding the timing and magnitude of the respiratory parameters. As those LVN profiles were derived using implantable means, this study indicates that the RnPs could serve as respiratory markers in implantable systems. © 2017 International Neuromodulation Society.

Left-Right Asymmetry of Maturation Rates in Human Embryonic Neural Development.

PubMed

de Kovel, Carolien G F; Lisgo, Steven; Karlebach, Guy; Ju, Jia; Cheng, Gang; Fisher, Simon E; Francks, Clyde

2017-08-01

Left-right asymmetry is a fundamental organizing feature of the human brain, and neuropsychiatric disorders such as schizophrenia sometimes involve alterations of brain asymmetry. As early as 8 weeks postconception, the majority of human fetuses move their right arms more than their left arms, but because nerve fiber tracts are still descending from the forebrain at this stage, spinal-muscular asymmetries are likely to play an important developmental role. We used RNA sequencing to measure gene expression levels in the left and right spinal cords, and the left and right hindbrains, of 18 postmortem human embryos aged 4 to 8 weeks postconception. Genes showing embryonic lateralization were tested for an enrichment of signals in genome-wide association data for schizophrenia. The left side of the embryonic spinal cord was found to mature faster than the right side. Both sides transitioned from transcriptional profiles associated with cell division and proliferation at earlier stages to neuronal differentiation and function at later stages, but the two sides were not in synchrony (p = 2.2 E-161). The hindbrain showed a left-right mirrored pattern compared with the spinal cord, consistent with the well-known crossing over of function between these two structures. Genes that showed lateralization in the embryonic spinal cord were enriched for association signals with schizophrenia (p = 4.3 E-05). These are the earliest stage left-right differences of human neural development ever reported. Disruption of the lateralized developmental program may play a role in the genetic susceptibility to schizophrenia. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Causal Role of Motor Simulation in Turn-Taking Behavior.

PubMed

Hadley, Lauren V; Novembre, Giacomo; Keller, Peter E; Pickering, Martin J

2015-12-16

Overlap between sensory and motor representations has been documented for a range of human actions, from grasping (Rizzolatti et al., 1996b) to playing a musical instrument (Novembre and Keller, 2014). Such overlap suggests that individuals use motor simulation to predict the outcome of observed actions (Wolpert, 1997). Here we investigate motor simulation as a basis of human communication. Using a musical turn-taking task, we show that pianists call on motor representations of their partner's part to predict when to come in for their own turn. Pianists played alternating solos with a videoed partner, and double-pulse transcranial magnetic stimulation was applied around the turn-switch to temporarily disrupt processing in two cortical regions implicated previously in different forms of motor simulation: (1) the dorsal premotor cortex (dPMC), associated with automatic motor resonance during passive observation of hand actions, especially when the actions are familiar (Lahav et al., 2007); and (2) the supplementary motor area (SMA), involved in active motor imagery, especially when the actions are familiar (Baumann et al., 2007). Stimulation of the right dPMC decreased the temporal accuracy of pianists' (right-hand) entries relative to sham when the partner's (left-hand) part had been rehearsed previously. This effect did not occur for dPMC stimulation without rehearsal or for SMA stimulation. These findings support the role of the dPMC in predicting the time course of observed actions via resonance-based motor simulation during turn-taking. Because turn-taking spans multiple modes of human interaction, we suggest that simulation is a foundational mechanism underlying the temporal dynamics of joint action. Even during passive observation, seeing or hearing somebody execute an action from within our repertoire activates motor cortices of our brain. But what is the functional relevance of such "motor simulation"? By combining a musical duet task with a real

Rhynchophylline from Uncaria rhynchophylla functionally turns delayed rectifiers into A-Type K+ channels.

PubMed

Chou, Chun-Hsiao; Gong, Chi-Li; Chao, Chia-Chia; Lin, Chia-Huei; Kwan, Chiu-Yin; Hsieh, Ching-Liang; Leung, Yuk-Man

2009-05-22

Rhynchophylline (1), a neuroprotective agent isolated from the traditional Chinese medicinal herb Uncaria rhynchophylla, was shown to affect voltage-gated K(+) (Kv) channel slow inactivation in mouse neuroblastoma N2A cells. Extracellular 1 (30 microM) accelerated the slow decay of Kv currents and shifted the steady-state inactivation curve to the left. Intracellular dialysis of 1 did not accelerate the slow current decay, suggesting that this compound acts extracellularly. In addition, the percent blockage of Kv currents by this substance was independent of the degree of depolarization and the intracellular K(+) concentration. Therefore, 1 did not appear to directly block the outer channel pore, with the results obtained suggesting that it drastically accelerated Kv channel slow inactivation. Interestingly, 1 also shifted the activation curve to the left. This alkaloid also strongly accelerated slow inactivation and caused a left shift of the activation curve of Kv1.2 channels heterologously expressed in HEK293 cells. Thus, this compound functionally turned delayed rectifiers into A-type K(+) channels.

Effects of Wearing NBC (Nuclear, Biological and Chemical) Protective Clothing in the Heat on Detection of Visual Signals

DTIC Science & Technology

1985-02-01

agents, as well as nuclear weaponry. In the face of’ such threats, the United States Army has developed equinment and clothing systems designed to...AD_ REPORT NO. T7185 EFFECTS OF WEARING NBC PROTECTIVE CLOTHING IN THE HEAT ON DETECTION OF VISUAL SIGNALS U S ARMY RESEARCH INSTITUTE N OF...CATALOG NUMBER T7/•5 ( 4. TITLE (and Subtitle) 5. TYPE OF REPORT & PERIOD COVERED Effects of Wearing NBC Protective Clothing in the Technical Report Heat

LL-37 attenuates inflammatory impairment via mTOR signaling-dependent mitochondrial protection.

PubMed

Sun, Wenyan; Zheng, Yan; Lu, Zhuoyang; Wang, Hui; Feng, Zhihui; Wang, Juan; Xiao, Shengxiang; Liu, Feng; Liu, Jiankang

2014-09-01

The human cationic antimicrobial protein LL-37 is a multifunctional host defense peptide with a wide range of immunomodulatory activities. Previous work has shown that LL-37 exerts both pro- and anti-inflammatory effects. The role of mitochondria in the skin inflammatory effects of LL-37 has not been well studied. Therefore, our aim was to investigate the immunomodulatory effect of LL-37 in HaCaT cells and to delineate the underlying mechanisms related to mitochondrial function. Immunohistochemistry results from tissue microarrays showed strong cytoplasmic LL-37 staining in inflammatory cells in chronic dermatic inflammation. Using exogenous LL-37 stimulation and LL-37 knockdown and overexpression, LL-37 was demonstrated to dramatically reduce the mRNA levels and protein secretion of inflammatory cytokines including IL-6, IL-8, IL-1α and tumor necrosis factor-α (TNF-α), which are induced by lipopolysaccharides (LPS). The anti-inflammatory effects of LL-37 are dependent upon its ability to increase mitochondrial biogenesis and to maintain mitochondrial homeostasis. Furthermore, we observed that LL-37 enhances the LPS-induced phosphorylation of extracellular signal-regulated kinase (ERK1/2) and mammalian target of rapamycin (mTOR). The mTOR inhibitor rapamycin can neutralize the protective effects of LL-37 on mitochondria. In conclusion, these results suggest that high LL-37 expression levels correlate with chronic skin inflammation; mitochondrial dysfunction occurs in HaCaT cells during inflammation; and LL-37 attenuates inflammatory impairment by stimulating mitochondrial biogenesis and protecting mitochondrial function, which are dependent upon mTOR signaling. These findings provide new insights into targeting mitochondria with LL-37 to prevent skin inflammatory reactions. Copyright © 2014 Elsevier Ltd. All rights reserved.

Induction motor inter turn fault detection using infrared thermographic analysis

NASA Astrophysics Data System (ADS)

Singh, Gurmeet; Anil Kumar, T. Ch.; Naikan, V. N. A.

2016-07-01

Induction motors are the most commonly used prime movers in industries. These are subjected to various environmental, thermal and load stresses that ultimately reduces the motor efficiency and later leads to failure. Inter turn fault is the second most commonly observed faults in the motors and is considered the most severe. It can lead to the failure of complete phase and can even cause accidents, if left undetected or untreated. This paper proposes an online and non invasive technique that uses infrared thermography, in order to detect the presence of inter turn fault in induction motor drive. Two methods have been proposed that detect the fault and estimate its severity. One method uses transient thermal monitoring during the start of motor and other applies pseudo coloring technique on infrared image of the motor, after it reaches a thermal steady state. The designed template for pseudo-coloring is in acquiescence with the InterNational Electrical Testing Association (NETA) thermographic standard. An index is proposed to assess the severity of the fault present in the motor.

Abortion foes get turn to ask Supreme Court for constitutional protection.

PubMed

Denniston, L

1994-04-28

The US Supreme Court began hearing arguments on the constitutionality of a Florida judge's order which placed limits on anti-abortion protesting. This case will be the last abortion--related decision for Justice Harry A. Blackmun, who was the author of the original decision granting the right to abortion in Roe vs. Wade, before retiring from the Court in September 1994. Anti-abortion activists claim 1st Amendment protection, much the same as Dr. Martin Luther King's marches in advancing Blacks' civil rights. The case involved a Melbourne abortion clinic. The murder of Dr. Gunn outside an abortion clinic in Pensacola, Florida, will be used to support the need for protection from extremist violence. The conflict appears to be over the right to save women's right to abortion and over simple, peaceful protests and prayers against abortion. One anti-abortion foe, affiliated with Operational Rescue and initiating the appeal to the Supreme Court, is scheduled to testify before the Court: Judy Madsen, a protester who has counseled outside clinics. Ms. Madsen says she is exercising her freedom to protect human life. Other testimony will come from Reverend Ed Martin of Ocala, Rescue America's founder, and Shirley Hobbs, a homemaker from Orlando. Representation will be made by lawyer Matthew Staver, who will argue that the ruling was directed to a political position. Other support will come from religious and anti-abortion groups and the AFL-CIO. Testifying for the clinic, the Aware Women's Center for Choice, will be the owner and operator Patricia Baird Windle. Over the past 5 years, the Melbourne Clinic had been a target for the nationwide anti-abortion campaign by Operation Rescue. Because of the conflicting rulings between the Florida Supreme Court, which ruled to keep protesters away from clinic grounds and staff homes, and 11th US Circuit Court of Appeals ruling of unconstitutionality, no protection is afforded the clinic. Previous protection had occurred due to a 1992

Lattice modeling and calibration with turn-by-turn orbit data

NASA Astrophysics Data System (ADS)

Huang, Xiaobiao; Sebek, Jim; Martin, Don

2010-11-01

A new method that explores turn-by-turn beam position monitor (BPM) data to calibrate lattice models of accelerators is proposed. The turn-by-turn phase space coordinates at one location of the ring are first established using data from two BPMs separated by a simple section with a known transfer matrix, such as a drift space. The phase space coordinates are then tracked with the model to predict positions at other BPMs, which can be compared to measurements. The model is adjusted to minimize the difference between the measured and predicted orbit data. BPM gains and rolls are included as fitting variables. This technique can be applied to either the entire or a section of the ring. We have tested the method experimentally on a part of the SPEAR3 ring.

The differential effects of acute right- vs. left-sided vestibular failure on brain metabolism.

PubMed

Becker-Bense, Sandra; Dieterich, Marianne; Buchholz, Hans-Georg; Bartenstein, Peter; Schreckenberger, Mathias; Brandt, Thomas

2014-07-01

The human vestibular system is represented in the brain bilaterally, but it has functional asymmetries, i.e., a dominance of ipsilateral pathways and of the right hemisphere in right-handers. To determine if acute right- or left-sided unilateral vestibular neuritis (VN) is associated with differential patterns of brain metabolism in areas representing the vestibular network and the visual-vestibular interaction, patients with acute VN (right n = 9; left n = 13) underwent resting state (18)F-FDG PET once in the acute phase and once 3 months later after central vestibular compensation. The contrast acute vs. chronic phase showed signal differences in contralateral vestibular areas and the inverse contrast in visual cortex areas, both more pronounced in VN right. In VN left additional regions were found in the cerebellar hemispheres and vermis bilaterally, accentuated in severe cases. In general, signal changes appeared more pronounced in patients with more severe vestibular deficits. Acute phase PET data of patients compared to that of age-matched healthy controls disclosed similarities to these patterns, thus permitting the interpretation that the signal changes in vestibular temporo-parietal areas reflect signal increases, and in visual areas, signal decreases. These data imply that brain activity in the acute phase of right- and left-sided VN exhibits different compensatory patterns, i.e., the dominant ascending input is shifted from the ipsilateral to the contralateral pathways, presumably due to the missing ipsilateral vestibular input. The visual-vestibular interaction patterns were preserved, but were of different prominence in each hemisphere and more pronounced in patients with right-sided failure and more severe vestibular deficits.

Tissue Damage Signaling Is a Prerequisite for Protective Neutrophil Recruitment to Microbial Infection in Zebrafish.

PubMed

Huang, Cong; Niethammer, Philipp

2018-05-15

Tissue damage and infection are deemed likewise triggers of innate immune responses. But whereas neutrophil responses to microbes are generally protective, neutrophil recruitment into damaged tissues without infection is deleterious. Why neutrophils respond to tissue damage and not just to microbes is unknown. Is it a flaw of the innate immune system that persists because evolution did not select against it, or does it provide a selective advantage? Here we dissect the contribution of tissue damage signaling to antimicrobial immune responses in a live vertebrate. By intravital imaging of zebrafish larvae, a powerful model for innate immunity, we show that prevention of tissue damage signaling upon microbial ear infection abrogates leukocyte chemotaxis and reduces animal survival, at least in part, through suppression of cytosolic phospholipase A 2 (cPla 2 ), which integrates tissue damage- and microbe-derived cues. Thus, microbial cues are insufficient, and damage signaling is essential for antimicrobial neutrophil responses in zebrafish. Copyright © 2018 Elsevier Inc. All rights reserved.

Turn Basin Construction

NASA Image and Video Library

2017-06-14

Modifications are underway at the Launch Complex 39 turn basin wharf at NASA's Kennedy Space Center in Florida to prepare for the arrival of the agency's massive Space Launch System (SLS) core booster aboard the barge Pegasus. Construction workers with Southeast Cherokee Construction Inc. work to shore up the turn basin area. A crane will be used to lift up precast concrete poles and position them to be driven to a depth of about 70 feet into the bedrock below the water around the turn basin. The upgrades are necessary to accommodate the 300,000-pound core booster aboard the modified Pegasus barge. The Ground Systems Development and Operations Program is overseeing the upgrades to the turn basin wharf.

Right/left assignment in drift chambers and proportional multiwire chambers (PWC's) using induced signals

DOEpatents

Walenta, Albert H.

1979-01-01

Improved multiwire chamber having means for resolving the left/right ambiguity in the location of an ionizing event. The chamber includes a plurality of spaced parallel anode wires positioned between spaced planar cathodes. Associated with each of the anode wires are a pair of localizing wires, one positioned on either side of the anode wire. The localizing wires are connected to a differential amplifier whose output polarity is determined by whether the ionizing event occurs to the right or left of the anode wire.

Optimism and the brain: trait optimism mediates the protective role of the orbitofrontal cortex gray matter volume against anxiety

PubMed Central

Hu, Yifan; Iordan, Alexandru D.; Moore, Matthew; Dolcos, Florin

2016-01-01

Converging evidence identifies trait optimism and the orbitofrontal cortex (OFC) as personality and brain factors influencing anxiety, but the nature of their relationships remains unclear. Here, the mechanisms underlying the protective role of trait optimism and of increased OFC volume against symptoms of anxiety were investigated in 61 healthy subjects, who completed measures of trait optimism and anxiety, and underwent structural scanning using magnetic resonance imaging. First, the OFC gray matter volume (GMV) was associated with increased optimism, which in turn was associated with reduced anxiety. Second, trait optimism mediated the relation between the left OFC volume and anxiety, thus demonstrating that increased GMV in this brain region protects against symptoms of anxiety through increased optimism. These results provide novel evidence about the brain–personality mechanisms protecting against anxiety symptoms in healthy functioning, and identify potential targets for preventive and therapeutic interventions aimed at reducing susceptibility and increasing resilience against emotional disturbances. PMID:26371336

Left-right asymmetry specification in amphioxus: review and prospects.

PubMed

Soukup, Vladimir

2017-01-01

Extant bilaterally symmetrical animals usually show asymmetry in the arrangement of their inner organs. However, the exaggerated left-right (LR) asymmetry in amphioxus represents a true peculiarity among them. The amphioxus larva shows completely disparate fates of left and right body sides, so that organs associated with pharynx are either positioned exclusively on the left or on the right side. Moreover, segmented paraxial structures such as muscle blocks and their neuronal innervation show offset arrangement between the sides making it difficult to propose any explanation or adaptivity to larval and adult life. First LR asymmetries can be traced back to an early embryonic period when morphological asymmetries are preceded by molecular asymmetries driven by the action of the Nodal signaling pathway. This review sums up recent advances in understanding LR asymmetry specification in amphioxus and proposes upstream events that may regulate asymmetric Nodal signaling. These events include the presence of the vertebrate-like LR organizer and a cilia-driven fluid flow that may be involved in the breaking of bilateral symmetry. The upstream pathways comprising the ion flux, Delta/Notch, Wnt/β-catenin and Wnt/PCP are hypothesized to regulate both formation of the LR organizer and expression of the downstream Nodal signaling pathway genes. These suggestions are in line with what we know from vertebrate and ambulacrarian LR axis specification and are directly testable by experimental manipulations. Thanks to the phylogenetic position of amphioxus, the proposed mechanisms may be helpful in understanding the evolution of LR axis specification across deuterostomes.

Suppression of microRNA-135b-5p protects against myocardial ischemia/reperfusion injury by activating JAK2/STAT3 signaling pathway in mice during sevoflurane anesthesia.

PubMed

Xie, Xiao-Juan; Fan, Dong-Mei; Xi, Kai; Chen, Ya-Wei; Qi, Peng-Wei; Li, Qian-Hui; Fang, Liang; Ma, Li-Gang

2017-06-30

The study aims to explore the effects of miR-135b-5p on myocardial ischemia/reperfusion (I/R) injuries by regulating Janus protein tyrosine kinase 2 (JAK2)/signal transducer and activator of transcription (STAT) signaling pathway by mediating inhalation anesthesia with sevoflurane. A sum of 120 healthy Wistar male mice was assigned into six groups. Left ventricular ejection fraction (LVEF) and left ventricular shortening fraction (LVSF) were detected. Cardiomyocyte apoptosis was determined by terminal dexynucleotidyl transferase mediated dUTP-biotin nick end labeling (TUNEL) assay. MiR-135b-5p expression, mRNA and protein expression of p-STAT3, p-JAK2, STAT3, JAK2, B-cell lymphoma-2 (Bcl-2) and Bcl-2 associated X protein B (Bax) were detected by quantitative real-time PCR (qRT-PCR) and Western blotting. Target relationship between miR-135b-5p and JAK2 was confirmed by dual-luciferase reporter assay. The other five groups exhibited increased cardiomyocyte necrosis, apoptosis, miR-135b-5p and Bax expression, mRNA expression of JAK2 and STAT3, and protein expression of p-STAT3 and p-JAK2 compared with the sham group, but showed decreased LVEF, LVFS, and Bcl-2 expression. Compared with the model and AG490 + Sevo groups, the Sevo, inhibitor + Sevo and inhibitor + AG490 + Sevo groups displayed reduced cardiomyocyte necrosis, apoptosis, miR-135b-5p and Bax expression, but displayed elevated mRNA expression of JAK2 and STAT3, protein expression of p-STAT3 and p-JAK2, LVEF, LVFS and Bcl-2 expression. Compared with the Sevo and inhibitor + AG490 + Sevo groups, the AG490 + Sevo group showed decreased LVEF, LVFS, Bcl-2 expression, mRNA expressions of JAK2 and STAT3, and protein expressions of p-STAT3 and p-JAK2, but increased cardiomyocyte necrosis, apoptosis, and Bax expressions. MiR-135b-5p negatively targetted JAK2. Inhibition of miR-135b-5p can protect against myocardial I/R injury by activating JAK2/STAT3 signaling pathway through mediation of inhalation anesthesia with

Quasi-phase-matching of the dual-band nonlinear left-handed metamaterial

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

Liu, Yahong, E-mail: yhliu@nwpu.edu.cn; Song, Kun; Gu, Shuai

2014-11-17

We demonstrate a type of nonlinear meta-atom creating a dual-band nonlinear left-handed metamaterial (DNLHM). The DNLHM operates at two distinct left-handed frequency bands where there is an interval of one octave between the two center frequencies. Under the illumination of a high-power signal at the first left-handed frequency band corresponding to fundamental frequency (FF), second-harmonic generation (SHG) is observed at the second left-handed band. This means that our DNLHM supports backward-propagating waves both at FF and second-harmonic (SH) frequency. We also experimentally demonstrate quasi-phase-matching configurations for the backward SHG. This fancy parametric process can significantly transmits the SH generated bymore » an incident FF wave.« less

[Effects of acupuncture at left and right Hegu (LI 4) for cerebral function laterality].

PubMed

Wang, Linying; Xu, Chunsheng; Zhu, Yifang; Li, Chuanfu; Yang, Jun

2015-08-01

To explore the cerebral function laterality of acupuncture at left and right Hegu (LI 4) by using functional magnetic resonance imaging (fMRI) and provide objective evidences for side selection of Hegu (LI 4) in the clinical application. Eighty healthy volunteers were randomly divided into a left-acupoint group and a right-acupoint group, and they were treated with acupuncture at left Hegu (LI 4) and right Hegu (LI 4) respectively. After the arrival of qi, the task-state fMRI data in both groups was collected, and analysis of functional neuroimages (AFNI) software was used to perform intra-group and between-group comparisons. After acupuncture, acupuncture feelings were recorded and MGH acupuncture sensation scale (MASS) was recorded. The difference of MASS between the two groups was not significant (P>0. 05). The result of left-acupoint group showed an increased signal on right cerebral hemisphere, while the right-acupoint group showed extensive signal changes in both cerebral hemispheres. The analysis between left-acupoint group and retroflex right-acupoint group showed differences in brain areas. The central effect of acupuncture at left and right Hegu (LI 4) is dissymmetry, indicating right hemisphere laterality. The right lobus insularis and cingulate gyrus may be the key regions in the acupuncture at Hegu (LI 4).

Innate immune signalling at intestinal mucosal surfaces: a fine line between host protection and destruction.

PubMed

Cario, Elke

2008-11-01

Emerging evidence underscores that inappropriate innate immune responses driven by commensals contribute to the pathogenesis of chronic inflammatory bowel diseases in genetically susceptible hosts. The present review focuses on defining the recently described mechanistic functions through which the innate immune signalling apparatus shapes mucosal homeostasis of the intestine in health and disease. Commensal-induced innate immune signalling actively drives at least six major interdependent functions to control homeostasis in the healthy intestinal mucosa: 1) barrier preservation, 2) inhibition of apoptosis and inflammation, 3) acceleration of wound repair and tissue regeneration, 4) exclusion of harmful pathogens through autophagy and other antimicrobial defenses, while 5) maintaining immune tolerance towards harmless commensals, and 6) linkage to adaptive immunity. Any disturbance of this peaceful and mutually beneficial host-commensal relationship may imbalance innate immune signalling, which predisposes to chronic intestinal inflammation and associated tumourigenesis in inflammatory bowel diseases. Recent advances have highlighted the complex mechanistics and functional diversity of innate immunity that paradoxically mediate both protective and destructive responses in the intestinal mucosa. Related signalling targets may offer novel therapeutic approaches in the treatment of inflammatory bowel diseases and inflammation-related cancer.

Guidelines for exclusive.

DOT National Transportation Integrated Search

1985-01-01

The objective of this research was to develop guidelines for the use of exclusive/permissive left-turn signal phasing. This was achieved by collecting data on traffic and roadway conditions for exclusive, exclusive/permissive, and permissive left-tur...

Tetramethylpyrazine Protects Against Oxygen-Glucose Deprivation-Induced Brain Microvascular Endothelial Cells Injury via Rho/Rho-kinase Signaling Pathway.

PubMed

Yang, Guang; Qian, Chen; Wang, Ning; Lin, Chenyu; Wang, Yan; Wang, Guangyun; Piao, Xinxin

2017-05-01

Tetramethylpyrazine (TMP, also known as Ligustrazine), which is isolated from Chinese Herb Medicine Ligustium wollichii Franchat (Chuan Xiong), has been widely used in China for the treatment of ischemic stroke by Chinese herbalists. Brain microvascular endothelial cells (BMECs) are the integral parts of the blood-brain barrier (BBB), protecting BMECs against oxygen-glucose deprivation (OGD) which is important for the treatment of ischemic stroke. Here, we investigated the protective mechanisms of TMP, focusing on OGD-injured BMECs and the Rho/Rho-kinase (Rho-associated kinases, ROCK) signaling pathway. The model of OGD-injured BMECs was established in this study. BMECs were identified by von Willebrand factor III staining and exposed to fasudil, or TMP at different concentrations (14.3, 28.6, 57.3 µM) for 2 h before 24 h of OGD injury. The effect of each treatment was examined by cell viability assays, measurement of intracellular reactive oxygen species (ROS), and transendothelial electric resistance and western blot analysis (caspase-3, endothelial nitric oxide synthase (eNOS), RhoA, Rac1). Our results show that TMP significantly attenuated apoptosis and the permeability of BMECs induced by OGD. In addition, TMP could notably down-regulate the characteristic proteins in Rho/ROCK signaling pathway such as RhoA and Rac1, which triggered abnormal changes of eNOS and ROS, respectively. Altogether, our results show that TMP has a strong protective effect against OGD-induced BMECs injury and suggest that the mechanism might be related to the inhibition of the Rho/ROCK signaling pathway.

Cost-Effectiveness of Percutaneous Closure of the Left Atrial Appendage in Atrial Fibrillation Based on Results from PROTECT AF vs. PREVAIL

PubMed Central

Freeman, James V.; Hutton, David W.; Barnes, Geoffrey D.; Zhu, Ruo P.; Owens, Douglas K.; Garber, Alan M.; Go, Alan S.; Hlatky, Mark A.; Heidenreich, Paul A.; Wang, Paul J.; Al-Ahmad, Amin; Turakhia, Mintu P.

2016-01-01

Background Randomized trials of left atrial appendage (LAA) closure with the Watchman device have shown varying results, and its cost-effectiveness compared to anticoagulation has not been evaluated using all available contemporary trial data. Methods and Results We used a Markov decision model to estimate lifetime quality-adjusted survival, costs, and cost-effectiveness of LAA closure with Watchman, compared directly with warfarin and indirectly with dabigatran, using data from the long-term (mean 3.8 year) follow-up of PROTECT AF and PREVAIL randomized trials. Using data from PROTECT AF, the incremental cost-effectiveness ratios (ICER) compared to warfarin and dabigatran were $20,486 and $23,422 per quality adjusted life year (QALY), respectively. Using data from PREVAIL, LAA closure was dominated by warfarin and dabigatran, meaning that it was less effective (8.44, 8.54, and 8.59 QALYs, respectively) and more costly. At a willingness-to-pay-threshold of $50,000 per QALY, LAA closure was cost-effective 90% and 9% of the time under PROTECT AF and PREVAIL assumptions, respectively. These results were sensitive to the rates of ischemic stroke and intracranial hemorrhage for LAA closure and medical anticoagulation. Conclusions Using data from the PROTECT AF trial, LAA closure with the Watchman device was cost-effective; using PREVAIL trial data, Watchman was more costly and less effective than warfarin and dabigatran. PROTECT AF enrolled more patients and has substantially longer follow-up time, allowing greater statistical certainty with the cost-effectiveness results. However, longer term trial results and post-marketing surveillance of major adverse events will be vital to determining the value of the Watchman in clinical practice. PMID:27307517

Adiponectin inhibits leptin signaling via multiple mechanisms to exert protective effects against hepatic fibrosis

PubMed Central

HANDY, Jeffrey A.; FU, Ping P.; KUMAR, Pradeep; MELLS, Jamie E.; SHARMA, Shvetank; SAXENA, Neeraj K.; ANANIA, Frank A.

2011-01-01

SYNOPSIS Adiponectin is protective against hepatic fibrosis, while leptin promotes fibrosis. In hepatic stellate cells (HSCs), leptin signals via a Janus Kinase 2/Signal Transducers and Activators of Transcription 3 (Jak2/Stat3) pathway, producing effects that enhance extracellular matrix deposition. Suppressors of Cytokine Signaling-3 (SOCS-3) and Protein Tyrosine Phosphatase-1B (PTP1B) are both negative regulators of Jak/Stat signaling, and recent studies demonstrated a role for adiponectin in regulating SOCS-3 expression. In this study we investigated mechanisms whereby adiponectin dampens leptin signaling and prevents excess ECM production. We treated culture-activated rat HSCs with recombinant adiponectin, leptin, both or neither, and also treated adiponectin knockout (Ad−/−) and wild-type mice with leptin and/or carbon tetrachloride (CCl4), or saline. We analyzed Jak2 and Ob-Rb phosphorylation, and PTP1B expression and activity. We also explored potential mechanisms through which adiponectin regulates SOCS-3/Ob-Rb association. Adiponectin inhibited leptin-stimulated Jak2 activation and Ob-Rb phosphorylation in HSCs, while both were increased in Ad−/− mice. Adiponectin stimulated PTP1B expression and activity, in vitro, while PTP1B expression was lower in Ad−/−mice than in wild-type mice. Adiponectin also promoted SOCS-3/Ob-R association, and blocked leptin-stimulated formation of extracellular TIMP-1/MMP-1 complexes, in vitro. These data suggest two novel mechanisms whereby adiponectin inhibits hepatic fibrosis: by promoting binding of SOCS-3 to Ob-Rb, and stimulating PTP1B expression and activity, thus inhibiting Jak2-Stat3 signaling at multiple points. PMID:21846328

Establishment of left-right asymmetry in vertebrate development: the node in mouse embryos.

PubMed

Komatsu, Yoshihiro; Mishina, Yuji

2013-12-01

Establishment of vertebrate left-right asymmetry is a critical process for normal embryonic development. After the discovery of genes expressed asymmetrically along the left-right axis in chick embryos in the mid 1990s, the molecular mechanisms responsible for left-right patterning in vertebrate embryos have been studied extensively. In this review article, we discuss the mechanisms by which the initial symmetry along the left-right axis is broken in the mouse embryo. We focus on the role of primary cilia and molecular mechanisms of ciliogenesis at the node when symmetry is broken and left-right asymmetry is established. The node is considered a signaling center for early mouse embryonic development, and the results we review here have led to a better understanding of how the node functions and establishes left-right asymmetry.

A statistical analysis of cervical auscultation signals from adults with unsafe airway protection.

PubMed

Dudik, Joshua M; Kurosu, Atsuko; Coyle, James L; Sejdić, Ervin

2016-01-22

Aspiration, where food or liquid is allowed to enter the larynx during a swallow, is recognized as the most clinically salient feature of oropharyngeal dysphagia. This event can lead to short-term harm via airway obstruction or more long-term effects such as pneumonia. In order to non-invasively identify this event using high resolution cervical auscultation there is a need to characterize cervical auscultation signals from subjects with dysphagia who aspirate. In this study, we collected swallowing sound and vibration data from 76 adults (50 men, 26 women, mean age 62) who underwent a routine videofluoroscopy swallowing examination. The analysis was limited to swallows of liquid with either thin (<5 cps) or viscous (≈300 cps) consistency and was divided into those with deep laryngeal penetration or aspiration (unsafe airway protection), and those with either shallow or no laryngeal penetration (safe airway protection), using a standardized scale. After calculating a selection of time, frequency, and time-frequency features for each swallow, the safe and unsafe categories were compared using Wilcoxon rank-sum statistical tests. Our analysis found that few of our chosen features varied in magnitude between safe and unsafe swallows with thin swallows demonstrating no statistical variation. We also supported our past findings with regard to the effects of sex and the presence or absence of stroke on cervical ausculation signals, but noticed certain discrepancies with regards to bolus viscosity. Overall, our results support the necessity of using multiple statistical features concurrently to identify laryngeal penetration of swallowed boluses in future work with high resolution cervical auscultation.

Mimicry by asx- and ST-turns of the four main types of beta-turn in proteins.

PubMed

Duddy, William J; Nissink, J Willem M; Allen, Frank H; Milner-White, E James

2004-11-01

Hydrogen-bonded beta-turns in proteins occur in four categories: type I (the most common), type II, type II', and type I'. Asx-turns resemble beta-turns, in that both have an NH. . .OC hydrogen bond forming a ring of 10 atoms. Serine and threonine side chains also commonly form hydrogen-bonded turns, here called ST-turns. Asx-turns and ST-turns can be categorized into four classes, based on side chain rotamers and the conformation of the central turn residue, which are geometrically equivalent to the four types of beta-turns. We propose asx- and ST-turns be named using the type I, II, I', and II' beta-turn nomenclature. Using this, the frequency of occurrence of both asx- and ST-turns is: type II' > type I > type II > type I', whereas for beta-turns it is type I > type II > type I' > type II'. Almost all type II asx-turns occur as a recently described three residue feature named an asx-nest.

Mimicry by asx- and ST-turns of the four main types of β-turn in proteins

PubMed Central

Duddy, William J.; Nissink, J. Willem M.; Allen, Frank H.; Milner-White, E. James

2004-01-01

Hydrogen-bonded β-turns in proteins occur in four categories: type I (the most common), type II, type II’, and type I’. Asx-turns resemble β-turns, in that both have an NH. . .OC hydrogen bond forming a ring of 10 atoms. Serine and threonine side chains also commonly form hydrogen-bonded turns, here called ST-turns. Asx-turns and ST-turns can be categorized into four classes, based on side chain rotamers and the conformation of the central turn residue, which are geometrically equivalent to the four types of β-turns. We propose asx- and ST-turns be named using the type I, II, I’, and II’ β-turn nomenclature. Using this, the frequency of occurrence of both asx- and ST-turns is: type II’ > type I > type II > type I’, whereas for β-turns it is type I > type II > type I’ > type II’. Almost all type II asx-turns occur as a recently described three residue feature named an asx-nest. PMID:15459339

Factor X/Xa elicits protective signaling responses in endothelial cells directly via PAR-2 and indirectly via endothelial protein C receptor-dependent recruitment of PAR-1.

PubMed

Bae, Jong-Sup; Yang, Likui; Rezaie, Alireza R

2010-11-05

We recently demonstrated that the Gla domain-dependent interaction of protein C with endothelial protein C receptor (EPCR) leads to dissociation of the receptor from caveolin-1 and recruitment of PAR-1 to a protective signaling pathway. Thus, the activation of PAR-1 by either thrombin or PAR-1 agonist peptide elicited a barrier-protective response if endothelial cells were preincubated with protein C. In this study, we examined whether other vitamin K-dependent coagulation protease zymogens can modulate PAR-dependent signaling responses in endothelial cells. We discovered that the activation of both PAR-1 and PAR-2 in endothelial cells pretreated with factor FX (FX)-S195A, but not other procoagulant protease zymogens, also results in initiation of protective intracellular responses. Interestingly, similar to protein C, FX interaction with endothelial cells leads to dissociation of EPCR from caveolin-1 and recruitment of PAR-1 to a protective pathway. Further studies revealed that, FX activated by factor VIIa on tissue factor bearing endothelial cells also initiates protective signaling responses through the activation of PAR-2 independent of EPCR mobilization. All results could be recapitulated by the receptor agonist peptides to both PAR-1 and PAR-2. These results suggest that a cross-talk between EPCR and an unknown FX/FXa receptor, which does not require interaction with the Gla domain of FX, recruits PAR-1 to protective signaling pathways in endothelial cells.

Right turn on red : a report to the Governor and General Assembly of Virginia.

DOT National Transportation Integrated Search

1975-01-01

The Commonwealth of Virginia implemented the sign permissive or "eastern" rule permitting right turns on red traffic signals where designated by sign in 1972. In 1975, as a result of the growing national trend toward employing the general permissive ...

Flight set 360L007 (STS-33R) field joint protection system, thermal protection system, and systems tunnel components, volume 7

NASA Technical Reports Server (NTRS)

1990-01-01

The performance of the thermal protection system, field joint protection system, and systems tunnel components of flight set 360L007 is presented as evaluated by postflight hardware inspection. The condition of both motors was similar to previous flights. Four aft edge strikes were noted on the ground environment instrumentation thermal protection system. The hits all left a clean substrate, indicating that the damage was caused by nozzle severance debris and/or water impact. No National Space Transportation System debris criteria for missing thermal protection system were violated. Two problem reports were written against the field joint protection system. The first concerned two cracks in the K5NA closeout over the trunnion/vent valve location on the left-hand aft field joint. A similar condition was observed on Flight 5 (360H005). The second problem report referred to a number of small surface cracks between two impact marks on the left-hand forward field joint. Neither area exhibited loose material or any abnormal heat effects, and they have no impact on flight safety.

Npom-Protected NONOate Enables Light-Triggered NO/cGMP Signalling in Primary Vascular Smooth Muscle Cells.

PubMed

Stroppel, Anna S; Paolillo, Michael; Ziegler, Thomas; Feil, Robert; Stafforst, Thorsten

2018-06-18

Diazeniumdiolates (NONOates) are a class of nitric-oxide-releasing substances widely used in studies of NO/cGMP signalling. Because spatiotemporal control is highly desirable for such purposes, we have synthesised a new Npom-caged pyrrolidine NONOate. A kinetic analysis together with a Griess assay showed the photodependent release of NO with high quantum yield (UV light). In primary vascular smooth muscle cells (VSMCs), our compound was reliably able to induce fast increases in cGMP, as measured with a genetically encoded FRET-based cGMP sensor and further validated by the phosphorylation of the downstream target vasodilator-stimulated phosphoprotein (VASP). Thanks to their facile synthesis, good decaging kinetics and capability to activate cGMP signalling in a fast and efficient manner, Npom-protected NONOates allow for improved spatiotemporal control of NO/cGMP signalling. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Celecoxib exerts protective effects in the vascular endothelium via COX-2-independent activation of AMPK-CREB-Nrf2 signalling.

PubMed

Al-Rashed, Fahad; Calay, Damien; Lang, Marie; Thornton, Clare C; Bauer, Andrea; Kiprianos, Allan; Haskard, Dorian O; Seneviratne, Anusha; Boyle, Joseph J; Schönthal, Alex H; Wheeler-Jones, Caroline P; Mason, Justin C

2018-04-19

Although concern remains about the athero-thrombotic risk posed by cyclo-oxygenase (COX)-2-selective inhibitors, recent data implicates rofecoxib, while celecoxib appears equivalent to NSAIDs naproxen and ibuprofen. We investigated the hypothesis that celecoxib activates AMP kinase (AMPK) signalling to enhance vascular endothelial protection. In human arterial and venous endothelial cells (EC), and in contrast to ibuprofen and naproxen, celecoxib induced the protective protein heme oxygenase-1 (HO-1). Celecoxib derivative 2,5-dimethyl-celecoxib (DMC) which lacks COX-2 inhibition also upregulated HO-1, implicating a COX-2-independent mechanism. Celecoxib activated AMPKα (Thr172) and CREB-1 (Ser133) phosphorylation leading to Nrf2 nuclear translocation. Importantly, these responses were not reproduced by ibuprofen or naproxen, while AMPKα silencing abrogated celecoxib-mediated CREB and Nrf2 activation. Moreover, celecoxib induced H-ferritin via the same pathway, and increased HO-1 and H-ferritin in the aortic endothelium of mice fed celecoxib (1000 ppm) or control chow. Functionally, celecoxib inhibited TNF-α-induced NF-κB p65 (Ser536) phosphorylation by activating AMPK. This attenuated VCAM-1 upregulation via induction of HO-1, a response reproduced by DMC but not ibuprofen or naproxen. Similarly, celecoxib prevented IL-1β-mediated induction of IL-6. Celecoxib enhances vascular protection via AMPK-CREB-Nrf2 signalling, a mechanism which may mitigate cardiovascular risk in patients prescribed celecoxib. Understanding NSAID heterogeneity and COX-2-independent signalling will ultimately lead to safer anti-inflammatory drugs.

Age-related modifications in steering behaviour: effects of base-of-support constraints at the turn point.

PubMed

Paquette, Maxime R; Fuller, Jason R; Adkin, Allan L; Vallis, Lori Ann

2008-09-01

This study investigated the effects of altering the base of support (BOS) at the turn point on anticipatory locomotor adjustments during voluntary changes in travel direction in healthy young and older adults. Participants were required to walk at their preferred pace along a 3-m straight travel path and continue to walk straight ahead or turn 40 degrees to the left or right for an additional 2-m. The starting foot and occasionally the gait starting point were adjusted so that participants had to execute the turn using a cross-over step with a narrow BOS or a lead-out step with a wide BOS. Spatial and temporal gait variables, magnitudes of angular segmental movement, and timing and sequencing of body segment reorientation were similar despite executing the turn with a narrow or wide BOS. A narrow BOS during turning generated an increased step width in the step prior to the turn for both young and older adults. Age-related changes when turning included reduced step velocity and step length for older compared to young adults. Age-related changes in the timing and sequencing of body segment reorientation prior to the turn point were also observed. A reduction in walking speed and an increase in step width just prior to the turn, combined with a delay in motion of the center of mass suggests that older adults used a more cautious combined foot placement and hip strategy to execute changes in travel direction compared to young adults. The results of this study provide insight into mobility constraints during a common locomotor task in older adults.

Transcriptional targets of DAF-16 insulin signaling pathway protect C. elegans from extreme hypertonic stress.

PubMed

Lamitina, S Todd; Strange, Kevin

2005-02-01

All cells adapt to hypertonic stress by regulating their volume after shrinkage, by accumulating organic osmolytes, and by activating mechanisms that protect against and repair hypertonicity-induced damage. In mammals and nematodes, inhibition of signaling from the DAF-2/IGF-1 insulin receptor activates the DAF-16/FOXO transcription factor, resulting in increased life span and resistance to some types of stress. We tested the hypothesis that inhibition of insulin signaling in Caenorhabditis elegans also increases hypertonic stress resistance. Genetic inhibition of DAF-2 or its downstream target, the AGE-1 phosphatidylinositol 3-kinase, confers striking resistance to a normally lethal hypertonic shock in a DAF-16-dependent manner. However, insulin signaling is not inhibited by or required for adaptation to hypertonic conditions. Microarray studies have identified 263 genes that are transcriptionally upregulated by DAF-16 activation. We identified 14 DAF-16-upregulated genes by RNA interference screening that are required for age-1 hypertonic stress resistance. These genes encode heat shock proteins, proteins of unknown function, and trehalose synthesis enzymes. Trehalose levels were elevated approximately twofold in age-1 mutants, but this increase was insufficient to prevent rapid hypertonic shrinkage. However, age-1 animals unable to synthesize trehalose survive poorly under hypertonic conditions. We conclude that increased expression of proteins that protect eukaryotic cells against environmental stress and/or repair stress-induced molecular damage confers hypertonic stress resistance in C. elegans daf-2/age-1 mutants. Elevated levels of solutes such as trehalose may also function in a cytoprotective manner. Our studies provide novel insights into stress resistance in animal cells and a foundation for new studies aimed at defining molecular mechanisms underlying these essential processes.

Turning Fiction Into Non-fiction for Signal-to-Noise Ratio Estimation -- The Time-Multiplexed and Adaptive Split-Symbol Moments Estimator

NASA Astrophysics Data System (ADS)

Simon, M.; Dolinar, S.

2005-08-01

A means is proposed for realizing the generalized split-symbol moments estimator (SSME) of signal-to-noise ratio (SNR), i.e., one whose implementation on the average allows for a number of subdivisions (observables), 2L, per symbol beyond the conventional value of two, with other than an integer value of L. In theory, the generalized SSME was previously shown to yield optimum performance for a given true SNR, R, when L=R/sqrt(2) and thus, in general, the resulting estimator was referred to as the fictitious SSME. Here we present a time-multiplexed version of the SSME that allows it to achieve its optimum value of L as above (to the extent that it can be computed as the average of a sum of integers) at each value of SNR and as such turns fiction into non-fiction. Also proposed is an adaptive algorithm that allows the SSME to rapidly converge to its optimum value of L when in fact one has no a priori information about the true value of SNR.

Caffeic acid phenethyl ester protects against glucocorticoid-induced osteoporosis in vivo: Impact on oxidative stress and RANKL/OPG signals

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

Tolba, Mai F.

Glucocorticoid-induced osteoporosis (GIO) is one of the most common causes of secondary osteoporosis. Given that glucocorticoids are considered as a main component of the treatment protocols for a variety of inflammation and immune-mediated diseases besides its use as adjuvant to several chemotherapeutic agents, it is crucial to find ways to overcome this critical adverse effect. Caffeic acid phenethyl ester (CAPE), which is a natural compound derived from honeybee propolis displayed promising antiosteoporotic effects against mechanical bone injury in various studies. The current work aimed at investigating the potential protective effect of CAPE against GIO in vivo with emphasis on themore » modulation of oxidative status and receptor activator of NF-kB ligand (RANKL)/osteoprotegrin (OPG) signaling. The results showed that CAPE opposed dexamethasone (DEX)-mediated alterations in bone histology and tartarate-resistant acid phosphatase (TRAP) activity. In addition, CAPE restored oxidative balance, Runt-related transcription factor 2 (RunX2) expression and reduced caspase-3 activity in femur tissues. Co-administration of CAPE with DEX normalized RANKL/OPG ratio and Akt activation indicating a reduction in DEX-osteoclastogenesis. In conclusion, concurrent treatment of CAPE with DEX exhibited promising effects in the protection against DEX-induced osteoporosis through opposing osteoclastogenesis and protecting osteoblasts. The potent antioxidant activity of CAPE is, at least in part, involved in its anti-apoptotic effects and modulation of RunX2 and RANKL/OPG signals. The use of CAPE-enriched propolis formulas is strongly recommended for patients on chronic glucocorticoid therapy to help in the attenuation of GIO. - Highlights: • Caffeic acid phenethyl ester (CAPE) counteracts DEX-induced osteoporosis. • CAPE hinders DEX-induced alterations in oxidation parameters as GSH, SOD and MDA. • CAPE opposes osteoclastogenesis via suppressing RANL/OPG ratio and Akt

49 CFR 218.29 - Alternate methods of protection.

Code of Federal Regulations, 2014 CFR

2014-10-01

... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RAILROAD OPERATING PRACTICES Blue Signal Protection of Workers § 218.29 Alternate methods of protection. Instead of providing blue signal protection for workers in accordance with § 218.27, the following methods for blue signal protection may be used: (a) When workers are...

49 CFR 218.29 - Alternate methods of protection.

Code of Federal Regulations, 2012 CFR

2012-10-01

... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RAILROAD OPERATING PRACTICES Blue Signal Protection of Workers § 218.29 Alternate methods of protection. Instead of providing blue signal protection for workers in accordance with § 218.27, the following methods for blue signal protection may be used: (a) When workers are...

49 CFR 218.29 - Alternate methods of protection.

Code of Federal Regulations, 2011 CFR

2011-10-01

... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RAILROAD OPERATING PRACTICES Blue Signal Protection of Workers § 218.29 Alternate methods of protection. Instead of providing blue signal protection for workers in accordance with § 218.27, the following methods for blue signal protection may be used: (a) When workers are...

49 CFR 218.29 - Alternate methods of protection.

Code of Federal Regulations, 2013 CFR

2013-10-01

... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RAILROAD OPERATING PRACTICES Blue Signal Protection of Workers § 218.29 Alternate methods of protection. Instead of providing blue signal protection for workers in accordance with § 218.27, the following methods for blue signal protection may be used: (a) When workers are...

A variant of fibroblast growth factor receptor 2 (Fgfr2) regulates left-right asymmetry in zebrafish.

PubMed

Liu, Da-Wei; Hsu, Chia-Hao; Tsai, Su-Mei; Hsiao, Chung-Der; Wang, Wen-Pin

2011-01-01

Many organs in vertebrates are left-right asymmetrical located. For example, liver is at the right side and stomach is at the left side in human. Fibroblast growth factor (Fgf) signaling is important for left-right asymmetry. To investigate the roles of Fgfr2 signaling in zebrafish left-right asymmetry, we used splicing blocking morpholinos to specifically block the splicing of fgfr2b and fgfr2c variants, respectively. We found that the relative position of the liver and the pancreas were disrupted in fgfr2c morphants. Furthermore, the left-right asymmetry of the heart became random. Expression pattern of the laterality controlling genes, spaw and pitx2c, also became random in the morphants. Furthermore, lefty1 was not expressed in the posterior notochord, indicating that the molecular midline barrier had been disrupted. It was also not expressed in the brain diencephalon. Kupffer's vesicle (KV) size became smaller in fgfr2c morphants. Furthermore, KV cilia were shorter in fgfr2c morphants. We conclude that the fgfr2c isoform plays an important role in the left-right asymmetry during zebrafish development.

A Variant of Fibroblast Growth Factor Receptor 2 (Fgfr2) Regulates Left-Right Asymmetry in Zebrafish

PubMed Central

Liu, Da-Wei; Hsu, Chia-Hao; Tsai, Su-Mei; Hsiao, Chung-Der; Wang, Wen-Pin

2011-01-01

Many organs in vertebrates are left-right asymmetrical located. For example, liver is at the right side and stomach is at the left side in human. Fibroblast growth factor (Fgf) signaling is important for left-right asymmetry. To investigate the roles of Fgfr2 signaling in zebrafish left-right asymmetry, we used splicing blocking morpholinos to specifically block the splicing of fgfr2b and fgfr2c variants, respectively. We found that the relative position of the liver and the pancreas were disrupted in fgfr2c morphants. Furthermore, the left-right asymmetry of the heart became random. Expression pattern of the laterality controlling genes, spaw and pitx2c, also became random in the morphants. Furthermore, lefty1 was not expressed in the posterior notochord, indicating that the molecular midline barrier had been disrupted. It was also not expressed in the brain diencephalon. Kupffer's vesicle (KV) size became smaller in fgfr2c morphants. Furthermore, KV cilia were shorter in fgfr2c morphants. We conclude that the fgfr2c isoform plays an important role in the left-right asymmetry during zebrafish development. PMID:21747958

Combined Blockade of Interleukin-1α and -1β Signaling Protects Mice from Cognitive Dysfunction after Traumatic Brain Injury

PubMed Central

Newell, Elizabeth A.; Todd, Brittany P.; Mahoney, Jolonda; Pieper, Andrew A.; Ferguson, Polly J.

2018-01-01

Abstract Diffuse activation of interleukin-1 inflammatory cytokine signaling after traumatic brain injury (TBI) elicits progressive neurodegeneration and neuropsychiatric dysfunction, and thus represents a potential opportunity for therapeutic intervention. Although interleukin (IL)-1α and IL-1β both activate the common type 1 IL-1 receptor (IL-1RI), they manifest distinct injury-specific roles in some models of neurodegeneration. Despite its potential relevance to treating patients with TBI, however, the individual contributions of IL-1α and IL-1β to TBI-pathology have not been previously investigated. To address this need, we applied genetic and pharmacologic approaches in mice to dissect the individual contributions of IL-1α, IL-β, and IL-1RI signaling to the pathophysiology of fluid percussion–mediated TBI, a model of mixed focal and diffuse TBI. IL-1RI ablation conferred a greater protective effect on brain cytokine expression and cognitive function after TBI than did individual IL-1α or IL-1β ablation. This protective effect was recapitulated by treatment with the drug anakinra, a recombinant naturally occurring IL-1RI antagonist. Our data thus suggest that broad targeting of IL-1RI signaling is more likely to reduce neuroinflammation and preserve cognitive function after TBI than are approaches that individually target IL-1α or IL-1β signaling. PMID:29662944

Combined Blockade of Interleukin-1α and -1β Signaling Protects Mice from Cognitive Dysfunction after Traumatic Brain Injury.

PubMed

Newell, Elizabeth A; Todd, Brittany P; Mahoney, Jolonda; Pieper, Andrew A; Ferguson, Polly J; Bassuk, Alexander G

2018-01-01

Diffuse activation of interleukin-1 inflammatory cytokine signaling after traumatic brain injury (TBI) elicits progressive neurodegeneration and neuropsychiatric dysfunction, and thus represents a potential opportunity for therapeutic intervention. Although interleukin (IL)-1α and IL-1β both activate the common type 1 IL-1 receptor (IL-1RI), they manifest distinct injury-specific roles in some models of neurodegeneration. Despite its potential relevance to treating patients with TBI, however, the individual contributions of IL-1α and IL-1β to TBI-pathology have not been previously investigated. To address this need, we applied genetic and pharmacologic approaches in mice to dissect the individual contributions of IL-1α, IL-β, and IL-1RI signaling to the pathophysiology of fluid percussion-mediated TBI, a model of mixed focal and diffuse TBI. IL-1RI ablation conferred a greater protective effect on brain cytokine expression and cognitive function after TBI than did individual IL-1α or IL-1β ablation. This protective effect was recapitulated by treatment with the drug anakinra, a recombinant naturally occurring IL-1RI antagonist. Our data thus suggest that broad targeting of IL-1RI signaling is more likely to reduce neuroinflammation and preserve cognitive function after TBI than are approaches that individually target IL-1α or IL-1β signaling.

Turning breech babies after 34 weeks: the if, how, & when of turning breech babies.

PubMed

Cohain, Judy Slome

2007-01-01

Techniques for turning a term breech baby are 1). External cephalic version (ECV) using hands and ultrasound only; 2). Acupuncture point stimulation, by needle or moxibustion; 3). Chiropractic "Webster" technique; 4). Hypnotherapy; and 5). Special exercises. Fifty % of breech fetuses at 34 weeks will turn by themselves to head down by 38 weeks. Therefore, to be considered effective, a technique for turning breech must turn the baby and keep it turned more than 50% of the time. Only ECV with an experienced practitioner has been documented to have a greater than 50% success rate at 37 weeks; in 95% of cases the head stays down. Most women experience the fetus turning by hand as quick but very painful. "Unstable lie" is sometimes used as a baseless excuse for inducing labor after the baby turns from breech to head down. (judyslome@hotmail.com).

Neurons in the barrel cortex turn into processing whisker and odor signals: a cellular mechanism for the storage and retrieval of associative signals

PubMed Central

Wang, Dangui; Zhao, Jun; Gao, Zilong; Chen, Na; Wen, Bo; Lu, Wei; Lei, Zhuofan; Chen, Changfeng; Liu, Yahui; Feng, Jing; Wang, Jin-Hui

2015-01-01

Associative learning and memory are essential to logical thinking and cognition. How the neurons are recruited as associative memory cells to encode multiple input signals for their associated storage and distinguishable retrieval remains unclear. We studied this issue in the barrel cortex by in vivo two-photon calcium imaging, electrophysiology, and neural tracing in our mouse model that the simultaneous whisker and olfaction stimulations led to odorant-induced whisker motion. After this cross-modal reflex arose, the barrel and piriform cortices connected. More than 40% of barrel cortical neurons became to encode odor signal alongside whisker signal. Some of these neurons expressed distinct activity patterns in response to acquired odor signal and innate whisker signal, and others encoded similar pattern in response to these signals. In the meantime, certain barrel cortical astrocytes encoded odorant and whisker signals. After associative learning, the neurons and astrocytes in the sensory cortices are able to store the newly learnt signal (cross-modal memory) besides the innate signal (native-modal memory). Such associative memory cells distinguish the differences of these signals by programming different codes and signify the historical associations of these signals by similar codes in information retrievals. PMID:26347609

Quaternion-Based Signal Analysis for Motor Imagery Classification from Electroencephalographic Signals.

PubMed

Batres-Mendoza, Patricia; Montoro-Sanjose, Carlos R; Guerra-Hernandez, Erick I; Almanza-Ojeda, Dora L; Rostro-Gonzalez, Horacio; Romero-Troncoso, Rene J; Ibarra-Manzano, Mario A

2016-03-05

Quaternions can be used as an alternative to model the fundamental patterns of electroencephalographic (EEG) signals in the time domain. Thus, this article presents a new quaternion-based technique known as quaternion-based signal analysis (QSA) to represent EEG signals obtained using a brain-computer interface (BCI) device to detect and interpret cognitive activity. This quaternion-based signal analysis technique can extract features to represent brain activity related to motor imagery accurately in various mental states. Experimental tests in which users where shown visual graphical cues related to left and right movements were used to collect BCI-recorded signals. These signals were then classified using decision trees (DT), support vector machine (SVM) and k-nearest neighbor (KNN) techniques. The quantitative analysis of the classifiers demonstrates that this technique can be used as an alternative in the EEG-signal modeling phase to identify mental states.

Quaternion-Based Signal Analysis for Motor Imagery Classification from Electroencephalographic Signals

PubMed Central

Batres-Mendoza, Patricia; Montoro-Sanjose, Carlos R.; Guerra-Hernandez, Erick I.; Almanza-Ojeda, Dora L.; Rostro-Gonzalez, Horacio; Romero-Troncoso, Rene J.; Ibarra-Manzano, Mario A.

2016-01-01

Quaternions can be used as an alternative to model the fundamental patterns of electroencephalographic (EEG) signals in the time domain. Thus, this article presents a new quaternion-based technique known as quaternion-based signal analysis (QSA) to represent EEG signals obtained using a brain-computer interface (BCI) device to detect and interpret cognitive activity. This quaternion-based signal analysis technique can extract features to represent brain activity related to motor imagery accurately in various mental states. Experimental tests in which users where shown visual graphical cues related to left and right movements were used to collect BCI-recorded signals. These signals were then classified using decision trees (DT), support vector machine (SVM) and k-nearest neighbor (KNN) techniques. The quantitative analysis of the classifiers demonstrates that this technique can be used as an alternative in the EEG-signal modeling phase to identify mental states. PMID:26959029

Adiponectin inhibits leptin signalling via multiple mechanisms to exert protective effects against hepatic fibrosis.

PubMed

Handy, Jeffrey A; Fu, Ping P; Kumar, Pradeep; Mells, Jamie E; Sharma, Shvetank; Saxena, Neeraj K; Anania, Frank A

2011-12-15

Adiponectin is protective against hepatic fibrosis, whereas leptin promotes fibrosis. In HSCs (hepatic stellate cells), leptin signals via a JAK2 (Janus kinase 2)/STAT3 (signal transducer and activator of transcription 3) pathway, producing effects that enhance ECM (extracellular matrix) deposition. SOCS-3 (suppressor of cytokine signalling-3) and PTP1B (protein tyrosine phosphatase 1B) are both negative regulators of JAK/STAT signalling, and recent studies have demonstrated a role for adiponectin in regulating SOCS-3 expression. In the present study we investigate mechanisms whereby adiponectin dampens leptin signalling and prevents excess ECM production. We treated culture-activated rat HSCs with recombinant adiponectin, leptin, both or neither, and also treated adiponectin knockout (Ad-/-) and wild-type mice with leptin and/or carbon tetrachloride (CCl4) or saline. We analyse JAK2 and Ob-Rb (long form of the leptin receptor) phosphorylation, and PTP1B expression and activity. We also explore potential mechanisms through which adiponectin regulates SOCS-3-Ob-Rb association. Adiponectin inhibits leptin-stimulated JAK2 activation and Ob-Rb phosphorylation in HSCs, whereas both were increased in Ad-/- mice. Adiponectin stimulates PTP1B expression and activity in vitro, whereas PTP1B expression was lower in Ad-/-mice than in wild-type mice. Adiponectin also promotes SOCS-3-Ob-R association and blocks leptin-stimulated formation of extracellular TIMP-1 (tissue inhibitor of metalloproteinases-1)-MMP-1 (matrix metalloproteinase-1) complexes in vitro. These results suggest two novel mechanisms whereby adiponectin inhibits hepatic fibrosis: (i) by promoting binding of SOCS-3 to Ob-Rb, and (ii) by stimulating PTP1B expression and activity, thus inhibiting JAK2/STAT3 signalling at multiple points.

Diastolic blood pressure-estimated left ventricular dp/dt.

PubMed

Yilmaz, Hüseyin; Minareci, Kenan; Kabukçu, Mehmet; Sancaktar, Oktay

2002-02-01

Peak dp/dt is one of the best isovolumic phase indexes of the myocardial contractile state requiring invasive procedures or presence of mitral regurgitation severe enough to measure in clinical practice by Doppler echocardiography. In this study, we sought the correlation between two noninvasive methods of measurements for left ventricular dp/dt-diastolic blood pressure- (DBP) estimated and continuous-wave Doppler-derived dp/dt-min electrocardiographic/echocardiographic study to emphasize the clinical feasibility of the DBP-estimated method. Thirty-six randomized patients (27 male, 9 female; 58 +/- 8 years) with mild mitral regurgitation were enrolled in this study. DBP-estimated dp/dt was calculated from DBP minus the left ventricular end-diastolic pressure (LVEDP) over the isovolumetric contraction time (IVCT). LVEDP was assumed to be 10 mmHg for all patients. Doppler-determined left ventricular dp/dt was derived from the continuous-wave Doppler spectrum of mitral regurgitation jet by dividing the magnitude of the left ventricular atrial pressure gradient rise between 1 mm/sec-3 mm/sec of mitral regurgitant velocity signal by the time taken for this change. Left ventricular dp/dt by Doppler was 1122 +/- 303 mmHg/sec and blood pressure-estimated dp/dt was 1063 +/- 294 mmHg/sec. There was a high correlation (r = 0.97, P < 0.001) of dp/dt between the two techniques. DBP and IVCT can generate left ventricular dp/dt without invasive procedures, even in the absence of mitral regurgitation in clinical practice.

Enhancement of endocannabinoid signaling protects against cocaine-induced neurotoxicity

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

Vilela, Luciano R.; Gobira, Pedro H.; Viana, Thercia G.

Cocaine is an addictive substance with a potential to cause deleterious effects in the brain. The strategies for treating its neurotoxicity, however, are limited. Evidence suggests that the endocannabinoid system exerts neuroprotective functions against various stimuli. Thus, we hypothesized that inhibition of fatty acid amide hydrolase (FAAH), the main enzyme responsible for terminating the actions of the endocannabinoid anandamide, reduces seizures and cell death in the hippocampus in a model of cocaine intoxication. Male Swiss mice received injections of endocannabinoid-related compounds followed by the lowest dose of cocaine that induces seizures, electroencephalographic activity and cell death in the hippocampus. Themore » molecular mechanisms were studied in primary cell culture of this structure. The FAAH inhibitor, URB597, reduced cocaine-induced seizures and epileptiform electroencephalographic activity. The cannabinoid CB{sub 1} receptor selective agonist, ACEA, mimicked these effects, whereas the antagonist, AM251, prevented them. URB597 also inhibited cocaine-induced activation and death of hippocampal neurons, both in animals and in primary cell culture. Finally, we investigated if the PI3K/Akt/ERK intracellular pathway, a cell surviving mechanism coupled to CB{sub 1} receptor, mediated these neuroprotective effects. Accordingly, URB597 injection increased ERK and Akt phosphorylation in the hippocampus. Moreover, the neuroprotective effect of this compound was reversed by the PI3K inhibitor, LY294002. In conclusion, the pharmacological facilitation of the anandamide/CB1/PI3K signaling protects the brain against cocaine intoxication in experimental models. This strategy may be further explored in the development of treatments for drug-induced neurotoxicity. - Highlights: • Cocaine toxicity is characterized by seizures and hippocampal cell death. • The endocannabinoid anandamide acts as a brain protective mechanism. • Inhibition of anandamide

Icariside II activates EGFR-Akt-Nrf2 signaling and protects osteoblasts from dexamethasone.

PubMed

Liu, Weidong; Mao, Li; Ji, Feng; Chen, Fengli; Wang, Shouguo; Xie, Yue

2017-01-10

The potential effect of icariside II on dexamethasone-induced osteoblast cell damages was evaluated here. In MC3T3-E1 osteoblastic cells and the primary murine osteoblasts, co-treatment with icariside II dramatically attenuated dexamethasone- induced cell death and apoptosis. Icariside II activated Akt signaling, which is required for its actions in osteoblasts. Akt inhibitors (LY294002, perifosine and MK-2206) almost abolished icariside II-induced osteoblast cytoprotection against dexamethasone. Further studies showed that icariside II activated Nrf2 signaling, downstream of Akt, to inhibit dexamethasone-induced reactive oxygen species (ROS) production in MC3T3-E1 cells and primary osteoblasts. On the other hand, Nrf2 shRNA knockdown inhibited icariside II-induced anti-dexamethasone cytoprotection in MC3T3-E1 cells. Finally, we showed that icariside II induced heparin-binding EGF (HB-EGF) production and EGFR trans-activation in MC3T3-E1 cells. EGFR inhibition, via anti-HB-EGF antibody, EGFR inhibitor AG1478 or EGFR shRNA knockdown, almost blocked icariside II-induced Akt-Nrf2 activation in MC3T3-E1 cells. Collectively, we conclude that icariside II activates EGFR-Akt-Nrf2 signaling and protects osteoblasts from dexamethasone. Icariside II might have translational value for the treatment of dexamethasone-associated osteoporosis/osteonecrosis.

Naringin Protects Against Cartilage Destruction in Osteoarthritis Through Repression of NF-κB Signaling Pathway.

PubMed

Zhao, Yunpeng; Li, Zhong; Wang, Wenhan; Zhang, Hui; Chen, Jianying; Su, Peng; Liu, Long; Li, Weiwei

2016-02-01

Naringin was previously reported as a multifunctional agent. Recently, naringin was found to play a protective role in various inflammatory conditions. However, the role of naringin in cartilage degeneration and osteoarthritis (OA) progression is still unknown. TNF-α is reported to play a detrimental role in OA. Herein, primary murine chondrocytes were isolated and cultured with stimulation of TNF-α, in the presence or absence of naringin treatment. As a result, naringin attenuated TNF-α-mediated inflammation and catabolism in chondrocyte. Besides, surgically induced OA mice models were established. Cartilage degradation and OA severity were evaluated using Safranin-O staining, immunohistochemistry, and ELISA. Moreover, levels of inflammatory cytokines and catabolic markers in OA were analyzed. Oral administration of naringin alleviated degradation of cartilage matrix and protected against OA development in the surgically induced OA models. Furthermore, the protective function of naringin in cartilage and chondrocyte was possibly due to suppression of NF-κB signaling pathway. Collectively, this study presents naringin as a potential target for the treatment of joint degenerative diseases, including OA.

Not just signal shutoff: the protective role of arrestin-1 in rod cells.

PubMed

Sommer, Martha E; Hofmann, Klaus Peter; Heck, Martin

2014-01-01

The retinal rod cell is an exquisitely sensitive single-photon detector that primarily functions in dim light (e.g., moonlight). However, rod cells must routinely survive light intensities more than a billion times greater (e.g., bright daylight). One serious challenge to rod cell survival in daylight is the massive amount of all-trans-retinal that is released by Meta II, the light-activated form of the photoreceptor rhodopsin. All-trans-retinal is toxic, and its condensation products have been implicated in disease. Our recent work has developed the concept that rod arrestin (arrestin-1), which terminates Meta II signaling, has an additional role in protecting rod cells from the consequences of bright light by limiting free all-trans-retinal. In this chapter we will elaborate upon the molecular mechanisms by which arrestin-1 serves as both a single-photon response quencher as well as an instrument of rod cell survival in bright light. This discussion will take place within the framework of three distinct functional modules of vision: signal transduction, the retinoid cycle, and protein translocation.

Turn Basin Construction

NASA Image and Video Library

2017-06-14

Modifications are underway at the Launch Complex 39 turn basin wharf at NASA's Kennedy Space Center in Florida to prepare for the arrival of the agency's massive Space Launch System (SLS) core stage aboard the barge Pegasus. Precast concrete poles are being driven to a depth of about 70 feet into the bedrock below the water around the turn basin. The upgrades are necessary to accommodate the increased weight of the core stage along with ground support and transportation equipment aboard the modified barge Pegasus. The Ground Systems Development and Operations Program is overseeing the upgrades to the turn basin wharf.

Systems and methods for photovoltaic string protection

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

Krein, Philip T.; Kim, Katherine A.; Pilawa-Podgurski, Robert C. N.

A system and method includes a circuit for protecting a photovoltaic string. A bypass switch connects in parallel to the photovoltaic string and a hot spot protection switch connects in series with the photovoltaic string. A first control signal controls opening and closing of the bypass switch and a second control signal controls opening and closing of the hot spot protection switch. Upon detection of a hot spot condition the first control signal closes the bypass switch and after the bypass switch is closed the second control signal opens the hot spot protection switch.

Dynamic regulation of canonical TGFβ signalling by endothelial transcription factor ERG protects from liver fibrogenesis.

PubMed

Dufton, Neil P; Peghaire, Claire R; Osuna-Almagro, Lourdes; Raimondi, Claudio; Kalna, Viktoria; Chuahan, Abhishek; Webb, Gwilym; Yang, Youwen; Birdsey, Graeme M; Lalor, Patricia; Mason, Justin C; Adams, David H; Randi, Anna M

2017-10-12

The role of the endothelium in protecting from chronic liver disease and TGFβ-mediated fibrosis remains unclear. Here we describe how the endothelial transcription factor ETS-related gene (ERG) promotes liver homoeostasis by controlling canonical TGFβ-SMAD signalling, driving the SMAD1 pathway while repressing SMAD3 activity. Molecular analysis shows that ERG binds to SMAD3, restricting its access to DNA. Ablation of ERG expression results in endothelial-to-mesenchymal transition (EndMT) and spontaneous liver fibrogenesis in EC-specific constitutive hemi-deficient (Erg cEC-Het ) and inducible homozygous deficient mice (Erg iEC-KO ), in a SMAD3-dependent manner. Acute administration of the TNF-α inhibitor etanercept inhibits carbon tetrachloride (CCL 4 )-induced fibrogenesis in an ERG-dependent manner in mice. Decreased ERG expression also correlates with EndMT in tissues from patients with end-stage liver fibrosis. These studies identify a pathogenic mechanism where loss of ERG causes endothelial-dependent liver fibrogenesis via regulation of SMAD2/3. Moreover, ERG represents a promising candidate biomarker for assessing EndMT in liver disease.The transcription factor ERG is key to endothelial lineage specification and vascular homeostasis. Here the authors show that ERG balances TGFβ signalling through the SMAD1 and SMAD3 pathways, protecting the endothelium from endothelial-to-mesenchymal transition and consequent liver fibrosis in mice via a SMAD3-dependent mechanism.

A Mechanistic Model of Early FcεRI Signaling: Lipid Rafts and the Question of Protection from Dephosphorylation

PubMed Central

Barua, Dipak; Goldstein, Byron

2012-01-01

We present a model of the early events in mast cell signaling mediated by FcεRI where the plasma membrane is composed of many small ordered lipid domains (rafts), surrounded by a non-order region of lipids consisting of the remaining plasma membrane. The model treats the rafts as transient structures that constantly form and breakup, but that maintain a fixed average number per cell. The rafts have a high propensity for harboring Lyn kinase, aggregated, but not unaggregated receptors, and the linker for the activation of T cells (LAT). Phosphatase activity in the rafts is substantially reduced compared to the nonraft region. We use the model to analyze published experiments on the rat basophilic leukemia (RBL)-2H3 cell line that seem to contradict the notion that rafts offer protection. In these experiments IgE was cross-linked with a multivalent antigen and then excess monovalent hapten was added to break-up cross-links. The dephosphorylation of the unaggregated receptor (nonraft associated) and of LAT (raft associated) were then monitored in time and found to decay at similar rates, leading to the conclusion that rafts offer no protection from dephosphorylation. In the model, because the rafts are transient, a protein that is protected while in a raft will be subject to dephosphorylation when the raft breaks up and the protein finds itself in the nonraft region of the membrane. We show that the model is consistent with the receptor and LAT dephosphorylation experiments while still allowing rafts to enhance signaling by providing substantial protection from phosphatases. PMID:23284735

Determination of linear optics functions from turn-by-turn data

NASA Astrophysics Data System (ADS)

Alexahin, Y.; Gianfelice-Wendt, E.

2011-10-01

A method for evaluation of coupled optics functions, detection of strong perturbing elements, determination of BPM calibration errors and tilts using turn-by-turn (TBT) data is presented as well as the new version of the Hamiltonian perturbation theory of betatron oscillations the method is based upon. An example of application of the considered method to the Tevatron is given.

Corydalis hendersonii Hemsl. protects against myocardial injury by attenuating inflammation and fibrosis via NF-κB and JAK2-STAT3 signaling pathways.

PubMed

Bai, Ruifeng; Yin, Xu; Feng, Xiao; Cao, Yuan; Wu, Yan; Zhu, Zhixiang; Li, Chun; Tu, Pengfei; Chai, Xingyun

2017-07-31

Corydalis hendersonii Hemsl. (CH) with heat clearing and detoxifying effects are well described in Tibetan folk medicine. It has been used for centuries in China largely for the treatment of high altitude polycythemia, a pathophysiological condition referred to "plethora" in Tibetan medicine, hypertension, hepatitis, edema, gastritis, and other infectious diseases. To investigate the cardioprotective effects of Corydalis hendersonii extract in an ICR mouse model of myocardial ischemic injury. Ethanol [85% (v/v)] extract of CH whole plant was prepared, and their chemical profile was analyzed with use of HPLC-DAD and IT-TOF-ESI-MS. A mouse model of AMI was established by ligation of the left ventricular dysfunction (LAD) coronary artery. Mice were randomly divided into six groups (n = 12 per group): sham group, model group, CH groups treated with three doses of CH (100, 200, and 400mg/kg, intragastric), and a positive control group (captopril, 16.67mg/kg, intragastric). Heart function was evaluated by measurement of ejection fraction (EF) and fractional shortening (FS) by echocardiography. Serum levels of creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH), plasma levels of angiotensin II (AngII), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1ß (IL-1ß) and expressions of matrix metalloproteinase-2 (MMP-2) and MMP-9 in the cardiac tissue homogenate, protein expressions of signal-transduction proteins, p65, IκBα, JAK2, and STAT3 in heart tissues were measured by ELISA and Western blot analyses. Inflammatory cell infiltration and changes in collagen deposition in the myocardial ischemic heart tissues were observed by histopathological examination. Platelet aggregation in vitro was also assessed. CH treatment showed a dose-dependent cardioprotective effect. It significantly reduced left ventricular end-diastolic diameter (LVEDd) and left ventricular end-diastolic diameter (LVEDs), improved EF and FS as compared to those in the model

Xenon Protects Against Septic Acute Kidney Injury via miR-21 Target Signaling Pathway.

PubMed

Jia, Ping; Teng, Jie; Zou, Jianzhou; Fang, Yi; Wu, Xie; Liang, Mingyu; Ding, Xiaoqiang

2015-07-01

Septic acute kidney injury is one of the most common and life-threatening complications in critically ill patients, and there is no approved effective treatment. We have shown xenon provides renoprotection against ischemia-reperfusion injury and nephrotoxicity in rodents via inhibiting apoptosis. Here, we studied the effects of xenon preconditioning on septic acute kidney injury and its mechanism. Experimental animal investigation. University research laboratory. Experiments were performed with male C57BL/6 mice, 10 weeks of age, weighing 20-25 g. We induced septic acute kidney injury by a single intraperitoneal injection of Escherichia coli lipopolysaccharide at a dose of 20 mg/kg. Mice were exposed for 2 hours to either 70% xenon or 70% nitrogen, 24 hours before the onset of septic acute kidney injury. In vivo knockdown of miR-21 was performed using locked nucleic acid-modified anti-miR, the role of miR-21 in renal protection conferred by the xenon preconditioning was examined, and miR-21 signaling pathways were analyzed. Xenon preconditioning provided morphologic and functional renoprotection, characterized by attenuation of renal tubular damage, apoptosis, and a reduction in inflammation. Furthermore, xenon treatment significantly upregulated the expression of miR-21 in kidney, suppressed proinflammatory factor programmed cell death protein 4 expression and nuclear factor-κB activity, and increased interleukin-10 production. Meanwhile, xenon preconditioning also suppressed the expression of proapoptotic protein phosphatase and tensin homolog deleted on chromosome 10, activating protein kinase B signaling pathway, subsequently increasing the expression of antiapoptotic B-cell lymphoma-2, and inhibiting caspase-3 activity. Knockdown of miR-21 upregulated its target effectors programmed cell death protein 4 and phosphatase and tensin homolog deleted on chromosome 10 expression, resulted in an increase in apoptosis, and exacerbated lipopolysaccharide

Xenon Protects Against Septic Acute Kidney Injury via miR-21 Target Signaling Pathway*

PubMed Central

Jia, Ping; Teng, Jie; Zou, Jianzhou; Fang, Yi; Wu, Xie; Liang, Mingyu

2015-01-01

Objectives: Septic acute kidney injury is one of the most common and life-threatening complications in critically ill patients, and there is no approved effective treatment. We have shown xenon provides renoprotection against ischemia-reperfusion injury and nephrotoxicity in rodents via inhibiting apoptosis. Here, we studied the effects of xenon preconditioning on septic acute kidney injury and its mechanism. Design: Experimental animal investigation. Setting: University research laboratory. Subjects: Experiments were performed with male C57BL/6 mice, 10 weeks of age, weighing 20–25 g. Interventions: We induced septic acute kidney injury by a single intraperitoneal injection of Escherichia coli lipopolysaccharide at a dose of 20 mg/kg. Mice were exposed for 2 hours to either 70% xenon or 70% nitrogen, 24 hours before the onset of septic acute kidney injury. In vivo knockdown of miR-21 was performed using locked nucleic acid-modified anti-miR, the role of miR-21 in renal protection conferred by the xenon preconditioning was examined, and miR-21 signaling pathways were analyzed. Measurements and Main Results: Xenon preconditioning provided morphologic and functional renoprotection, characterized by attenuation of renal tubular damage, apoptosis, and a reduction in inflammation. Furthermore, xenon treatment significantly upregulated the expression of miR-21 in kidney, suppressed proinflammatory factor programmed cell death protein 4 expression and nuclear factor-κB activity, and increased interleukin-10 production. Meanwhile, xenon preconditioning also suppressed the expression of proapoptotic protein phosphatase and tensin homolog deleted on chromosome 10, activating protein kinase B signaling pathway, subsequently increasing the expression of antiapoptotic B-cell lymphoma-2, and inhibiting caspase-3 activity. Knockdown of miR-21 upregulated its target effectors programmed cell death protein 4 and phosphatase and tensin homolog deleted on chromosome 10

Pharmacologic induction of epidermal melanin and protection against sunburn in a humanized mouse model.

PubMed

Amaro-Ortiz, Alexandra; Vanover, Jillian C; Scott, Timothy L; D'Orazio, John A

2013-09-07

Fairness of skin, UV sensitivity and skin cancer risk all correlate with the physiologic function of the melanocortin 1 receptor, a Gs-coupled signaling protein found on the surface of melanocytes. Mc1r stimulates adenylyl cyclase and cAMP production which, in turn, up-regulates melanocytic production of melanin in the skin. In order to study the mechanisms by which Mc1r signaling protects the skin against UV injury, this study relies on a mouse model with "humanized skin" based on epidermal expression of stem cell factor (Scf). K14-Scf transgenic mice retain melanocytes in the epidermis and therefore have the ability to deposit melanin in the epidermis. In this animal model, wild type Mc1r status results in robust deposition of black eumelanin pigment and a UV-protected phenotype. In contrast, K14-Scf animals with defective Mc1r signaling ability exhibit a red/blonde pigmentation, very little eumelanin in the skin and a UV-sensitive phenotype. Reasoning that eumelanin deposition might be enhanced by topical agents that mimic Mc1r signaling, we found that direct application of forskolin extract to the skin of Mc1r-defective fair-skinned mice resulted in robust eumelanin induction and UV protection (1). Here we describe the method for preparing and applying a forskolin-containing natural root extract to K14-Scf fair-skinned mice and report a method for measuring UV sensitivity by determining minimal erythematous dose (MED). Using this animal model, it is possible to study how epidermal cAMP induction and melanization of the skin affect physiologic responses to UV exposure.

Turn Basin Construction

NASA Image and Video Library

2017-06-14

Modifications are underway at the Launch Complex 39 turn basin wharf at NASA's Kennedy Space Center in Florida to prepare for the arrival of the agency's massive Space Launch System (SLS) core stage aboard the barge Pegasus. A crane will be used to lift up precast concrete poles and position them to be driven to a depth of about 70 feet into the bedrock below the water around the turn basin. The upgrades are necessary to accommodate the 300,000-pound core booster aboard the modified Pegasus barge. The Ground Systems Development and Operations Program is overseeing the upgrades to the turn basin wharf.

Neuropilin asymmetry mediates a left-right difference in habenular connectivity.

PubMed

Kuan, Yung-Shu; Yu, Hung-Hsiang; Moens, Cecilia B; Halpern, Marnie E

2007-03-01

The medial habenular nuclei of the zebrafish diencephalon, which lie bilateral to the pineal complex, exhibit left-right differences in their neuroanatomy, gene expression profiles and axonal projections to the unpaired midbrain target--the interpeduncular nucleus (IPN). Efferents from the left habenula terminate along the entire dorsoventral extent of the IPN, whereas axons from the right habenula project only to the ventral IPN. How this left-right difference in connectivity is established and the factors involved in differential target recognition are unknown. Prior to IPN innervation, we find that only the left habenula expresses the zebrafish homologue of Neuropilin1a (Nrp1a), a receptor for class III Semaphorins (Sema3s). Directional asymmetry of nrp1a expression relies on Nodal signaling and the presence of the left-sided parapineal organ. Loss of Nrp1a, through parapineal ablation or depletion by antisense morpholinos, prevents left habenular neurons from projecting to the dorsal IPN. Selective depletion of Sema3D, but not of other Sema family members, similarly disrupts innervation of the dorsal IPN. Conversely, Sema3D overexpression results in left habenular projections that extend to the dorsal IPN, as well as beyond the target. The results indicate that Sema3D acts in concert with Nrp1a to guide neurons on the left side of the brain to innervate the target nucleus differently than those on the right side.

Measuring zebrafish turning rate.

PubMed

Mwaffo, Violet; Butail, Sachit; di Bernardo, Mario; Porfiri, Maurizio

2015-06-01

Zebrafish is becoming a popular animal model in preclinical research, and zebrafish turning rate has been proposed for the analysis of activity in several domains. The turning rate is often estimated from the trajectory of the fish centroid that is output by commercial or custom-made target tracking software run on overhead videos of fish swimming. However, the accuracy of such indirect methods with respect to the turning rate associated with changes in heading during zebrafish locomotion is largely untested. Here, we compare two indirect methods for the turning rate estimation using the centroid velocity or position data, with full shape tracking for three different video sampling rates. We use tracking data from the overhead video recorded at 60, 30, and 15 frames per second of zebrafish swimming in a shallow water tank. Statistical comparisons of absolute turning rate across methods and sampling rates indicate that, while indirect methods are indistinguishable from full shape tracking, the video sampling rate significantly influences the turning rate measurement. The results of this study can aid in the selection of the video capture frame rate, an experimental design parameter in zebrafish behavioral experiments where activity is an important measure.

Neuroligin-3 protects retinal cells from H2O2-induced cell death via activation of Nrf2 signaling.

PubMed

Li, Xiu-Miao; Huang, Dan; Yu, Qing; Yang, Jian; Yao, Jin

2018-05-25

Intensified oxidative stress can cause severe damage to human retinal pigment epithelium (RPE) cells and retinal ganglion cells (RGCs). The potential effect of neuroligin-3 (NLGN3) against the process is studied here. Our results show that NLGN3 efficiently inhibited hydrogen peroxide (H 2 O 2 )-induced death and apoptosis in human RPE cells and RGCs. H 2 O 2 -induced reactive oxygen species (ROS) production, lipid peroxidation and DNA damage in retinal cells were alleviated by NLGN3. NLGN3 activated nuclear-factor-E2-related factor 2 (Nrf2) signaling, enabling Nrf2 protein stabilization, nuclear translocation and expression of key anti-oxidant enzymes (HO1, NOQ1 and GCLC) in RPE cells and RGCs. Further results demonstrate that NLGN3 activated Akt-mTORC1 signaling in retinal cells. Conversely, Akt-mTORC1 inhibitors (RAD001 and LY294002) reduced NLGN3-induced HO1, NOQ1 and GCLC mRNA expression. Significantly, Nrf2 silencing by targeted shRNAs reversed NLGN3-induced retinal cytoprotection against H 2 O 2 . We conclude that NLGN3 activates Nrf2 signaling to protect human retinal cells from H 2 O 2 . NLGN3 could be further tested as a valuable retinal protection agent. Copyright © 2018 Elsevier Inc. All rights reserved.

IL-17 receptor A signaling is protective in infection-stimulated periapical bone destruction.

PubMed

AlShwaimi, Emad; Berggreen, Ellen; Furusho, Hisako; Rossall, Jonathan Caleb; Dobeck, Justine; Yoganathan, Subbiah; Stashenko, Philip; Sasaki, Hajime

2013-08-15

IL-17 is a pleiotropic cytokine produced by Th17 T cells that induces a myriad of proinflammatory mediators. However, different models of inflammation report opposite functional roles of IL-17 signal in terms of its effects on bone destruction. In this study we determined the role of IL-17RA signal in bone resorption stimulated by dentoalveolar infections. Infrabony resorptive lesions were induced by surgical pulp exposure and microbial infection of mouse molar teeth. IL-17 was strongly induced in periapical tissues in wild-type (WT) mice by 7 d after the infection but was not expressed in uninfected mice. Dentoalveolar infections of IL-17RA knockout (KO) mice demonstrated significantly increased bone destruction and more abscess formation in the apical area compared with WT mice. Infected IL-17RA KO mice exhibited significantly increased neutrophils and macrophages compared with the WT littermates at day 21, suggesting a failure of transition from acute to chronic inflammation in the IL-17RA KO mice. The expression of IL-1 (both α and β isoforms) and MIP2 were significantly upregulated in the IL-17RA KO compared with WT mice at day 21 postinfection. The development of periapical lesions in IL-17RA KO mice was significantly attenuated by neutralization of IL-1β and MIP2. Taken together, these results demonstrate that IL-17RA signal seems to be protective against infection-induced periapical inflammation and bone destruction via suppression of neutrophil and mononuclear inflammation.

Turn Basin Construction

NASA Image and Video Library

2017-06-14

Modifications are underway at the Launch Complex 39 turn basin wharf at NASA's Kennedy Space Center in Florida to prepare for the arrival of the agency's massive Space Launch System (SLS) core stage aboard the barge Pegasus. Equipment is staged and a crane will be used to lift up precast concrete poles and position them to be driven to a depth of about 70 feet into the bedrock below the water around the turn basin. The upgrades are necessary to accommodate the increased weight of the core stage along with ground support and transportation equipment aboard the modified barge Pegasus. The Ground Systems Development and Operations Program is overseeing the upgrades to the turn basin wharf.

Turn Basin Construction

NASA Image and Video Library

2017-06-14

Modifications are underway at the Launch Complex 39 turn basin wharf at NASA's Kennedy Space Center in Florida to prepare for the arrival of the agency's massive Space Launch System (SLS) core stage aboard the barge Pegasus. A crane will be used to lift up precast concrete poles and position them to be driven to a depth of about 70 feet into the bedrock below the water around the turn basin. The upgrades are necessary to accommodate the increased weight of the core stage along with ground support and transportation equipment aboard the modified barge Pegasus. The Ground Systems Development and Operations Program is overseeing the upgrades to the turn basin wharf.

Optimism and the brain: trait optimism mediates the protective role of the orbitofrontal cortex gray matter volume against anxiety.

PubMed

Dolcos, Sanda; Hu, Yifan; Iordan, Alexandru D; Moore, Matthew; Dolcos, Florin

2016-02-01

Converging evidence identifies trait optimism and the orbitofrontal cortex (OFC) as personality and brain factors influencing anxiety, but the nature of their relationships remains unclear. Here, the mechanisms underlying the protective role of trait optimism and of increased OFC volume against symptoms of anxiety were investigated in 61 healthy subjects, who completed measures of trait optimism and anxiety, and underwent structural scanning using magnetic resonance imaging. First, the OFC gray matter volume (GMV) was associated with increased optimism, which in turn was associated with reduced anxiety. Second, trait optimism mediated the relation between the left OFC volume and anxiety, thus demonstrating that increased GMV in this brain region protects against symptoms of anxiety through increased optimism. These results provide novel evidence about the brain-personality mechanisms protecting against anxiety symptoms in healthy functioning, and identify potential targets for preventive and therapeutic interventions aimed at reducing susceptibility and increasing resilience against emotional disturbances. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Cathelicidin Signaling via the Toll-Like Receptor Protects Against Colitis in Mice

PubMed Central

Koon, Hon Wai; Shih, David Quan; Chen, Jeremy; Bakirtzi, Kyriaki; Hing, Tressia C; Law, Ivy; Ho, Samantha; Ichikawa, Ryan; Zhao, Dezheng; Xu, Hua; Gallo, Richard; Dempsey, Paul; Cheng, Genhong; Targan, Stephan R; Pothoulakis, Charalabos

2011-01-01

Background & Aims Cathelicidin (encoded by Camp) is an anti-microbial peptide in the innate immune system. We examined whether macrophages express cathelicidin in colons of mice with experimental colitis and patients with inflammatory bowel disease; we investigated its signaling mechanisms. Methods Quantitative, real-time, reverse transcription PCR, bacterial 16S PCR, immunofluorescence, and small interfering (si)RNA analyses were performed. Colitis was induced in mice using sodium dextran sulfate (DSS); levels of cathelicidin were measured in human primary monocytes. Results Expression of cathelicidin increased in the inflamed colonic mucosa of mice with DSS-induced colitis, compared with controls. Cathelicidin expression localized to mucosal macrophages in inflamed colon tissues of patients and mice. Exposure of human primary monocytes to E coli DNA induced expression of Camp mRNA, which required signaling by ERK; expression was reduced by siRNAs against toll-like receptor (TLR)9 and MyD88. Intracolonic administration of bacterial DNA to wild-type mice induced expression of cathelicidin in colons of control mice and mice with DSS-induced colitis. Colon expression of cathelicidin was significantly reduced in TLR9 −/− mice with DSS-induced colitis. Compared with wild-type mice, Camp −/− mice developed a more severe form of DSS-induced colitis, particularly after intracolonic administration of E coli DNA. Expression of cathelicidin from bone marrow-derived immune cells regulated DSS induction of colitis in transplantation studies in mice. Conclusions Cathelicidin protects against colitis induction in mice. Increased expression of cathelicidin in monocytes and experimental models of colitis involves activation of TLR9–ERK signaling by bacterial DNA. This pathway might be involved in pathogenesis of ulcerative colitis. PMID:21762664

Peptide design using alpha,beta-dehydro amino acids: from beta-turns to helical hairpins.

PubMed

Mathur, Puniti; Ramakumar, S; Chauhan, V S

2004-01-01

Incorporation of alpha,beta-dehydrophenylalanine (DeltaPhe) residue in peptides induces folded conformations: beta-turns in short peptides and 3(10)-helices in larger ones. A few exceptions-namely, alpha-helix or flat beta-bend ribbon structures-have also been reported in a few cases. The most favorable conformation of DeltaPhe residues are (phi,psi) approximately (-60 degrees, -30 degrees ), (-60 degrees, 150 degrees ), (80 degrees, 0 degrees ) or their enantiomers. DeltaPhe is an achiral and planar residue. These features have been exploited in designing DeltaPhe zippers and helix-turn-helix motifs. DeltaPhe can be incorporated in both right and left-handed helices. In fact, consecutive occurrence of three or more DeltaPhe amino acids induce left-handed screw sense in peptides containing L-amino acids. Weak interactions involving the DeltaPhe residue play an important role in molecular association. The C--H.O==C hydrogen bond between the DeltaPhe side-chain and backbone carboxyl moiety, pi-pi stacking interactions between DeltaPhe side chains belonging to enantiomeric helices have shown to stabilize folding. The unusual capability of a DeltaPhe ring to form the hub of multicentered interactions namely, a donor in aromatic C--H.pi and C--H.O==C and an acceptor in a CH(3).pi interaction suggests its exploitation in introducing long-range interactions in the folding of supersecondary structures. Copyright 2004 Wiley Periodicals, Inc. Biopolymers (Pept Sci), 2004

Future Orientation, Social Support, and Psychological Adjustment among Left-behind Children in Rural China: A Longitudinal Study.

PubMed

Su, Shaobing; Li, Xiaoming; Lin, Danhua; Zhu, Maoling

2017-01-01

Existing research has found that parental migration may negatively impact the psychological adjustment of left-behind children. However, limited longitudinal research has examined if and how future orientation (individual protective factor) and social support (contextual protective factor) are associated with the indicators of psychological adjustment (i.e., life satisfaction, school satisfaction, happiness, and loneliness) of left-behind children. In the current longitudinal study, we examined the differences in psychological adjustment between left-behind children and non-left behind children (comparison children) in rural areas, and explored the protective roles of future orientation and social support on the immediate (cross-sectional effects) and subsequent (lagged effects) status of psychological adjustment for both groups of children, respectively. The sample included 897 rural children ( M age = 14.09, SD = 1.40) who participated in two waves of surveys across six months. Among the participants, 227 were left-behind children with two parents migrating, 176 were with one parent migrating, and 485 were comparison children. Results showed that, (1) left-behind children reported lower levels of life satisfaction, school satisfaction, and happiness, as well as a higher level of loneliness in both waves; (2) After controlling for several demographics and characteristics of parental migration among left-behind children, future orientation significantly predicted life satisfaction, school satisfaction, and happiness in both cross-sectional and longitudinal regression models, as well as loneliness in the longitudinal regression analysis. Social support predicted immediate life satisfaction, school satisfaction, and happiness, as well as subsequent school satisfaction. Similar to left-behind children, comparison children who reported higher scores in future orientation, especially future expectation, were likely to have higher scores in most indicators of

Photoacoustic characterization of the left atrium wall: healthy and ablated tissue (Conference Presentation)

NASA Astrophysics Data System (ADS)

Iskander-Rizk, Sophinese; Kruizinga, Pieter; van der Steen, Antonius F. W.; van Soest, Gijs

2017-03-01

Radio-frequency ablation (RFA) creates a thermal lesion in the atrial wall, with clearly recognizable optical and structural changes to the tissue. This can be detected by photoacoustic (PA) imaging, and used for monitoring of lesion depth, lesion functionality, and limiting excessive ablation. Porcine left atrium tissue can be split into three visually distinguishable regions, a thick white endocardium, pinkish myocardium and a thin gelatinous epicardium. In this study, we characterize the layered left atrium tissue in terms of the relevant photoacoustic parameters (wavelength, frequency content, imaging depth, lesion contrast). Previous studies in the literature targeted the photoacoustic characterization of fresh and ablated ventricular myocardium in the range of 650nm to 900nm. In this study we target the characterization of fresh and ablated left atrial tissue from 410nm to 1000nm, including the endocardium and epicardium. We generate the photoacoustic signals using a tunable pulsed laser source, and record those signals using either a broadband 1 mm hydrophone or a L12-3v transducer connected to the Verasonics machine for more realistic conditions. Initial experiments on fresh porcine tissue show that the presence of the endocardium and epicardium layers do affect the photoacoustic signal received. The signal recorded is representative of the difference in optical and mechanical properties between the layers. Ablated and non-ablated tissue also present differences in spectra. The determined optical contrast could be used in the PA monitoring of RFA lesion to monitor the extension of the lesion to the edge of the myocardium-epicardium border avoiding complications related to over ablation.

Real-time detection and data acquisition system for the left ventricular outline. Ph.D. Thesis - Stanford Univ.

NASA Technical Reports Server (NTRS)

Reiber, J. H. C.

1976-01-01

To automate the data acquisition procedure, a real-time contour detection and data acquisition system for the left ventricular outline was developed using video techniques. The X-ray image of the contrast-filled left ventricle is stored for subsequent processing on film (cineangiogram), video tape or disc. The cineangiogram is converted into video format using a television camera. The video signal from either the TV camera, video tape or disc is the input signal to the system. The contour detection is based on a dynamic thresholding technique. Since the left ventricular outline is a smooth continuous function, for each contour side a narrow expectation window is defined in which the next borderpoint will be detected. A computer interface was designed and built for the online acquisition of the coordinates using a PDP-12 computer. The advantage of this system over other available systems is its potential for online, real-time acquisition of the left ventricular size and shape during angiocardiography.

Quality of life assessment in the randomized PROTECT AF (Percutaneous Closure of the Left Atrial Appendage Versus Warfarin Therapy for Prevention of Stroke in Patients With Atrial Fibrillation) trial of patients at risk for stroke with nonvalvular atrial fibrillation.

PubMed

Alli, Oluseun; Doshi, Shepal; Kar, Saibal; Reddy, Vivek; Sievert, Horst; Mullin, Chris; Swarup, Vijay; Whisenant, Brian; Holmes, David

2013-04-30

This study sought to assess quality of life parameters in a subset of patients enrolled in the PROTECT AF (Percutaneous Closure of the Left Atrial Appendage Versus Warfarin Therapy for Prevention of Stroke in Patients With Atrial Fibrillation) trial. The PROTECT AF (Percutaneous Closure of the Left Atrial Appendage Versus Warfarin Therapy for Prevention of Stroke in Patients With Atrial Fibrillation) trial demonstrated that in patients with nonvalvular atrial fibrillation (AF) and CHADS2 (congestive heart failure, hypertension, age, diabetes mellitus, and prior stroke, transient ischemic attack, or thromboembolism) score ≥1, a left atrial appendage closure device is noninferior to long-term warfarin for stroke prevention. Given this equivalency, quality of life (QOL) indicators are an important metric for evaluating these 2 different strategies. QOL using the Short-Form 12 Health Survey, version 2, measurement tool was obtained at baseline and 12 months in a subset of 547 patients in the PROTECT AF trial (361 device and 186 warfarin patients). The analysis cohort consisted of patients for whom either paired quality of life data were available after 12 months of follow-up or for patients who died. With the device, the total physical score improved in 34.9% and was unchanged in 29.9% versus warfarin in whom 24.7% were improved and 31.7% were unchanged (p = 0.01). Mental health improvement occurred in 33.0% of the device group versus 22.6% in the warfarin group (p = 0.06). There was a significant improvement in QOL in patients randomized to device for total physical score, physical function, and in physical role limitation compared to control. There were significant differences in the change in total physical score among warfarin naive and not-warfarin naive subgroups in the device group compared to control, but larger gains were seen with the warfarin naive subgroup with a 12-month change of 1.3 ± 8.8 versus -3.6 ± 6.7 (p = 0.0004) device compared to warfarin

Turn Basin Construction

NASA Image and Video Library

2017-06-14

Modifications are underway at the Launch Complex 39 turn basin wharf at NASA's Kennedy Space Center in Florida to prepare for the arrival of the agency's massive Space Launch System (SLS) core stage aboard the barge Pegasus. In the foreground is Tammy Kelly, site manager, with Southeast Cherokee Construction Inc. A crane will be used to lift up precast concrete poles and position them to be driven to a depth of about 70 feet into the bedrock below the water around the turn basin. The upgrades are necessary to accommodate the increased weight of the core stage along with ground support and transportation equipment aboard the modified barge Pegasus. The Ground Systems Development and Operations Program is overseeing the upgrades to the turn basin wharf.

Histone Modification Is Correlated With Reverse Left Ventricular Remodeling in Nonischemic Dilated Cardiomyopathy.

PubMed

Ito, Emiko; Miyagawa, Shigeru; Fukushima, Satsuki; Yoshikawa, Yasushi; Saito, Shunsuke; Saito, Tetsuya; Harada, Akima; Takeda, Maki; Kashiyama, Noriyuki; Nakamura, Yuki; Shiozaki, Motoko; Toda, Koichi; Sawa, Yoshiki

2017-11-01

Although implantation of a left ventricular assist device (LVAD) induces reverse remodeling of the left ventricle in end-stage nonischemic dilated cardiomyopathy (DCM), the underlying mechanism is not fully understood. It has been shown that epigenetic modification, such as methylation or acetylation of the histone, is one of the most important upstream signals in cardiac failure. This study hypothesized that histone profiles may be modified by LVAD implantation for end-stage nonischemic DCM, in association with reverse left ventricular remodeling. Hemodynamic changes associated with histone modification profiles in the left ventricle were comprehensively assessed in 14 patients with a diagnosis of end-stage nonischemic DCM. These patients underwent LVAD implantation and subsequent cardiac transplantation in our institution (Osaka University Hospital, Osaka, Japan). Samples of normal left ventricle from 3 different people were used as a control. After LVAD support for 2.5 ± 1.2 years, the study cohort showed a significant reverse remodeling of left ventricular function associated with histopathologic changes in the left ventricle, such as reduction of myocyte size. Although the left ventricle of the cohort histologically expressed less 3 histone methylation-related molecules (eg, H3 lysine 4 trimethylation [H3K4me3], H3 lysine 9 dimethylation [H3K9me2], and H3 lysine 9 trimethylation [H3K9me3]) compared with normal left ventricle, LVAD support reversed expression of these molecules, associated with up-regulation of H3 lysine 9 [H3K9] methyltransferase and suppressor of variegation 3-9 homologue 1 [SUV39H1] and with down-regulation of H3K9 demethylase and jumonji domains [JMJDs] in the LVAD-supported left ventricle. Moreover, expression of atrial natriuretic peptide and brain natriuretic peptide (ANP and BNP) was negatively correlated with that of H3K9me2 and H3K9me3. The epigenetic state of cardiac myocytes (eg, as histone methylation) was substantially modulated

Immediate Effects of Clock-Turn Strategy on the Pattern and Performance of Narrow Turning in Persons With Parkinson Disease.

PubMed

Yang, Wen-Chieh; Hsu, Wei-Li; Wu, Ruey-Meei; Lin, Kwan-Hwa

2016-10-01

Turning difficulty is common in people with Parkinson disease (PD). The clock-turn strategy is a cognitive movement strategy to improve turning performance in people with PD despite its effects are unverified. Therefore, this study aimed to investigate the effects of the clock-turn strategy on the pattern of turning steps, turning performance, and freezing of gait during a narrow turning, and how these effects were influenced by concurrent performance of a cognitive task (dual task). Twenty-five people with PD were randomly assigned to the clock-turn or usual-turn group. Participants performed the Timed Up and Go test with and without concurrent cognitive task during the medication OFF period. The clock-turn group performed the Timed Up and Go test using the clock-turn strategy, whereas participants in the usual-turn group performed in their usual manner. Measurements were taken during the 180° turn of the Timed Up and Go test. The pattern of turning steps was evaluated by step time variability and step time asymmetry. Turning performance was evaluated by turning time and number of turning steps. The number and duration of freezing of gait were calculated by video review. The clock-turn group had lower step time variability and step time asymmetry than the usual-turn group. Furthermore, the clock-turn group turned faster with fewer freezing of gait episodes than the usual-turn group. Dual task increased the step time variability and step time asymmetry in both groups but did not affect turning performance and freezing severity. The clock-turn strategy reduces turning time and freezing of gait during turning, probably by lowering step time variability and asymmetry. Dual task compromises the effects of the clock-turn strategy, suggesting a competition for attentional resources.Video Abstract available for more insights from the authors (see Supplemental Digital Content 1, http://links.lww.com/JNPT/A141).

Compound measure of hand-foot-eye preference masked opposite turning behavior in healthy right-handers and non-right-handers: technical comment on Mohr et al. (2003).

PubMed

Mohr, C; Bracha, H S

2004-10-01

A previous article reported opposite turning behavior in right-handers and non-right-handers (C. Mohr. T. Landis, H. S. Bracha, & P. Brugger, 2003). This observation appears contradictory to the 1st study on long-term spontaneous turning behavior in healthy participants (H. S. Bracha, D. J. Seitz, J. Otemaa, & S. D. Click, 1987). These latter authors found a complex interaction between hemispheric dominance, preferred turning side, and sex. C. Mohr et al. (2003) argued that the differentiation of the population in hemisphere-dominant groups by a compound measure of hand-foot-eye preference might have masked their recent finding. Thus, this commentary presents a reanalysis of the original data set (H. S. Bracha et al., 1987). Replicating recent observation, right-handers preferred left-sided turns; and non-righthanders, right-sided turns. This replication strengthens the proposition that handedness and turning behavior might depend on interhemispheric dopamine asymmetries. Copyright 2004 APA.

A Miniaturized Magnetic Induction Sensor Using Geomagnetism for Turn Count of Small-Caliber Ammunition

PubMed Central

Yoon, Sang-Hee; Lee, Seok-Woo; Lee, Young-Ho; Oh, Jong-Soo

2006-01-01

This paper presents a miniaturized magnetic induction sensor (MMIS), where geomagnetism and high rpm rotation of ammunition are used to detect the turn number of the ammunition for applications to small-caliber turn-counting fuzes. The MMIS, composed of cores and a coil, has a robust structure without moving parts to increase the shock survivability in a gunfire environment of ∼30,000 g's. The MMIS is designed and fabricated on the basis of the simulation results of an electromagnetic analysis tool, Maxwell® 3D. In the experimental study, static MMIS test using a solenoid-coil apparatus and dynamic MMIS test (firing test) have been made. The present MMIS has shown that an induction voltage of 6.5 mVp-p is generated at a magnetic flux density of 0.05 mT and a rotational velocity of 30,000 rpm. From the measured signal, MMIS has shown a signal-to-noise ratio of 44.0 dB, a nonlinearity of 0.59%, a frequency-normalized sensitivity of 0.256±0.010 V/T·Hz and a drift of 0.27% in the temperature range of -30∼+43°C. Firing test has shown that the MMIS can be used as a turn-counting sensor for small-caliber ammunition, verifying the shock survivability of the MMIS in a high-g environment.

Idiopathic pulmonary fibrosis (IPF) signaling pathways and protective roles of melatonin.

PubMed

Hosseinzadeh, Azam; Javad-Moosavi, Seyed Ali; Reiter, Russel J; Hemati, Karim; Ghaznavi, Habib; Mehrzadi, Saeed

2018-05-15

Idiopathic pulmonary fibrosis (IPF) is characterized by the progressive loss of lung function due to tissue scarring. A variety of pro-inflammatory and pro-fibrogenic factors including interleukin‑17A, transforming growth factor β, Wnt/β‑catenin, vascular endothelial growth factor, platelet-derived growth factor, fibroblast growth factors, endotelin‑1, renin angiotensin system and impaired caveolin‑1 function are involved in the IPF pathogenesis. Current therapies for IPF have some limitations and this highlights the need for effective therapeutic agents to treat this fatal disease. Melatonin and its metabolites are broad-spectrum antioxidants that not only remove reactive oxygen and nitrogen species by radical scavenging but also up-regulate the expression and activity of endogenous antioxidants. Via these actions, melatonin and its metabolites modulate a variety of molecular pathways in different pathophysiological conditions. Herein, we review the signaling pathways involved in the pathophysiology of IPF and the potentially protective effects of melatonin on these pathways. Copyright © 2018 Elsevier Inc. All rights reserved.

Revealing turning points in ecosystem functioning over the Northern Eurasian agricultural frontier.

PubMed

Horion, Stéphanie; Prishchepov, Alexander V; Verbesselt, Jan; de Beurs, Kirsten; Tagesson, Torbern; Fensholt, Rasmus

2016-08-01

The collapse of the Soviet Union in 1991 has been a turning point in the World history that left a unique footprint on the Northern Eurasian ecosystems. Conducting large scale mapping of environmental change and separating between naturogenic and anthropogenic drivers is a difficult endeavor in such highly complex systems. In this research a piece-wise linear regression method was used for breakpoint detection in Rain-Use Efficiency (RUE) time series and a classification of ecosystem response types was produced. Supported by earth observation data, field data, and expert knowledge, this study provides empirical evidence regarding the occurrence of drastic changes in RUE (assessment of the timing, the direction and the significance of these changes) in Northern Eurasian ecosystems between 1982 and 2011. About 36% of the study area (3.4 million km(2) ) showed significant (P < 0.05) trends and/or turning points in RUE during the observation period. A large proportion of detected turning points in RUE occurred around the fall of the Soviet Union in 1991 and in the following years which were attributed to widespread agricultural land abandonment. Our study also showed that recurrent droughts deeply affected vegetation productivity throughout the observation period, with a general worsening of the drought conditions in recent years. Moreover, recent human-induced turning points in ecosystem functioning were detected and attributed to ongoing recultivation and change in irrigation practices in the Volgograd region, and to increased salinization and increased grazing intensity around Lake Balkhash. The ecosystem-state assessment method introduced here proved to be a valuable support that highlighted hotspots of potentially altered ecosystems and allowed for disentangling human from climatic disturbances. © 2016 John Wiley & Sons Ltd.

Is resistant starch protective against colorectal cancer via modulation of the WNT signalling pathway?

PubMed

Malcomson, Fiona C; Willis, Naomi D; Mathers, John C

2015-08-01

Epidemiological and experimental evidence suggests that non-digestible carbohydrates (NDC) including resistant starch are protective against colorectal cancer. These anti-neoplastic effects are presumed to result from the production of the SCFA, butyrate, by colonic fermentation, which binds to the G-protein-coupled receptor GPR43 to regulate inflammation and other cancer-related processes. The WNT pathway is central to the maintenance of homeostasis within the large bowel through regulation of processes such as cell proliferation and migration and is frequently aberrantly hyperactivated in colorectal cancers. Abnormal WNT signalling can lead to irregular crypt cell proliferation that favours a hyperproliferative state. Butyrate has been shown to modulate the WNT pathway positively, affecting functional outcomes such as apoptosis and proliferation. Butyrate's ability to regulate gene expression results from epigenetic mechanisms, including its role as a histone deacetylase inhibitor and through modulating DNA methylation and the expression of microRNA. We conclude that genetic and epigenetic modulation of the WNT signalling pathway may be an important mechanism through which butyrate from fermentation of resistant starch and other NDC exert their chemoprotective effects.

Saxagliptin and Tadalafil Differentially Alter Cyclic Guanosine Monophosphate (cGMP) Signaling and Left Ventricular Function in Aortic-Banded Mini-Swine.

PubMed

Hiemstra, Jessica A; Lee, Dong I; Chakir, Khalid; Gutiérrez-Aguilar, Manuel; Marshall, Kurt D; Zgoda, Pamela J; Cruz Rivera, Noelany; Dozier, Daniel G; Ferguson, Brian S; Heublein, Denise M; Burnett, John C; Scherf, Carolin; Ivey, Jan R; Minervini, Gianmaria; McDonald, Kerry S; Baines, Christopher P; Krenz, Maike; Domeier, Timothy L; Emter, Craig A

2016-04-20

Cyclic guanosine monophosphate-protein kinase G-phosphodiesterase 5 signaling may be disturbed in heart failure (HF) with preserved ejection fraction, contributing to cardiac remodeling and dysfunction. The purpose of this study was to manipulate cyclic guanosine monophosphate signaling using the dipeptidyl-peptidase 4 inhibitor saxagliptin and phosphodiesterase 5 inhibitor tadalafil. We hypothesized that preservation of cyclic guanosine monophosphate cGMP signaling would attenuate pathological cardiac remodeling and improve left ventricular (LV) function. We assessed LV hypertrophy and function at the organ and cellular level in aortic-banded pigs. Concentric hypertrophy was equal in all groups, but LV collagen deposition was increased in only HF animals. Prevention of fibrotic remodeling by saxagliptin and tadalafil was correlated with neuropeptide Y plasma levels. Saxagliptin better preserved integrated LV systolic and diastolic function by maintaining normal LV chamber volumes and contractility (end-systolic pressure-volume relationship, preload recruitable SW) while preventing changes to early/late diastolic longitudinal strain rate. Function was similar to the HF group in tadalafil-treated animals including increased LV contractility, reduced chamber volume, and decreased longitudinal, circumferential, and radial mechanics. Saxagliptin and tadalafil prevented a negative cardiomyocyte shortening-frequency relationship observed in HF animals. Saxagliptin increased phosphodiesterase 5 activity while tadalafil increased cyclic guanosine monophosphate levels; however, neither drug increased downstream PKG activity. Early mitochondrial dysfunction, evident as decreased calcium-retention capacity and Complex II-dependent respiratory control, was present in both HF and tadalafil-treated animals. Both saxagliptin and tadalafil prevented increased LV collagen deposition in a manner related to the attenuation of increased plasma neuropeptide Y levels. Saxagliptin

Saikosaponin d protects against acetaminophen-induced hepatotoxicity by inhibiting NF-κB and STAT3 signaling.

PubMed

Liu, Aiming; Tanaka, Naoki; Sun, Lu; Guo, Bin; Kim, Jung-Hwan; Krausz, Kristopher W; Fang, Zhongze; Jiang, Changtao; Yang, Julin; Gonzalez, Frank J

2014-11-05

Overdose of acetaminophen (APAP) can cause acute liver injury that is sometimes fatal, requiring efficient pharmacological intervention. The traditional Chinese herb Bupleurum falcatum has been widely used for the treatment of several liver diseases in eastern Asian countries, and saikosaponin d (SSd) is one of its major pharmacologically-active components. However, the efficacy of Bupleurum falcatum or SSd on APAP toxicity remains unclear. C57/BL6 mice were administered SSd intraperitoneally once daily for 5days, followed by APAP challenge. Biochemical and pathological analysis revealed that mice treated with SSd were protected against APAP-induced hepatotoxicity. SSd markedly suppressed phosphorylation of nuclear factor kappa B (NF-κB) and signal transducer and activator of transcription 3 (STAT3) and reversed the APAP-induced increases in the target genes of NF-κB, such as pro-inflammatory cytokine Il6 and Ccl2, and those of STAT3, such as Socs3, Fga, Fgb and Fgg. SSd also enhanced the expression of the anti-inflammatory cytokine Il10 mRNA. Collectively, these results demonstrate that SSd protects mice from APAP-induced hepatotoxicity mainly through down-regulating NF-κB- and STAT3-mediated inflammatory signaling. This study unveils one of the possible mechanisms of hepatoprotection caused by Bupleurum falcatum and/or SSd. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Turn Basin Construction

NASA Image and Video Library

2017-06-14

Modifications are underway at the Launch Complex 39 turn basin wharf at NASA's Kennedy Space Center in Florida to prepare for the arrival of the agency's massive Space Launch System (SLS) core stage aboard the barge Pegasus. Tammy Kelly, in the center, site manager, with Southeast Cherokee Construction Inc. talks with construction workers. A crane will be used to lift up precast concrete poles and position them to be driven to a depth of about 70 feet into the bedrock below the water around the turn basin. The upgrades are necessary to accommodate the increased weight of the core stage along with ground support and transportation equipment aboard the modified barge Pegasus. The Ground Systems Development and Operations Program is overseeing the upgrades to the turn basin wharf.

An electronic circuit that detects left ventricular ejection events by processing the arterial pressure waveform

NASA Technical Reports Server (NTRS)

Gebben, V. D.; Webb, J. A., Jr.

1972-01-01

An electronic circuit for processing arterial blood pressure waveform signals is described. The circuit detects blood pressure as the heart pumps blood through the aortic valve and the pressure distribution caused by aortic valve closure. From these measurements, timing signals for use in measuring the left ventricular ejection time is determined, and signals are provided for computer monitoring of the cardiovascular system. Illustrations are given of the circuit and pressure waveforms.

Hyperin protects against LPS-induced acute kidney injury by inhibiting TLR4 and NLRP3 signaling pathways

PubMed Central

Chunzhi, Gong; Zunfeng, Li; Chengwei, Qin; Xiangmei, Bu; Jingui, Yu

2016-01-01

Hyperin is a flavonoid compound derived from Ericaceae, Guttifera, and Celastraceae that has been shown to have various biological effects, such as anti-inflammatory and anti-oxidant effects. However, there is no evidence to show the protective effects of hyperin on lipopolysaccharide (LPS)-induced acute kidney injury (AKI). Therefore, we investigated the protective effects and mechanism of hyperin on LPS-induced AKI in mice. The levels of TNF-α, IL-6, and IL-1β were tested by ELISA. The effects of hyperin on blood urea nitrogen (BUN) and serum creatinine were also detected. In addition, the expression of TLR4, NF-κB, and NLRP3 were detected by western blot analysis. The results showed that hyperin significantly inhibited LPS-induced TNF-α, IL-6, and IL-1β production. The levels of BUN and creatinine were also suppressed by hyperin. Furthermore, LPS-induced TLR4 expression and NF-κB activation were also inhibited by hyperin. In addition, treatment of hyperin dose-dependently inhibited LPS-induced NLRP3 signaling pathway. In conclusion, the results showed that hyperin inhibited LPS-induced inflammatory response by inhibiting TLR4 and NLRP3 signaling pathways. Hyperin has potential application prospects in the treatment of sepsis-induced AKI. PMID:27813491

An Active Insect Kinin Analog with 4-Aminopyroglutamate, A Novel cis-Peptide Bond, Type VI beta-Turn Motif

DTIC Science & Technology

2004-01-01

2004 Wiley Periodicals, Inc.* Biopolymers 75: 412–419, 2004 Keywords: 4-aminopyroglutamic acid ; cis-peptide bond; -turn mimetic; constrained insect...biological evaluation of an insect kinin analog containing a novel, (2S,4S)-4-aminopyroglutamic acid (APy) com- ponent (Figure 1) that theoretical and...cricket diuretic bioassay system. FIGURE 1 A comparison of the structures of the tetrazole ([CN4], left) and 4-aminopyroglu- tamic acid (APy; right

Hummingbirds control turning velocity using body orientation and turning radius using asymmetrical wingbeat kinematics

PubMed Central

Read, Tyson J. G.; Segre, Paolo S.; Middleton, Kevin M.; Altshuler, Douglas L.

2016-01-01

Turning in flight requires reorientation of force, which birds, bats and insects accomplish either by shifting body position and total force in concert or by using left–right asymmetries in wingbeat kinematics. Although both mechanisms have been observed in multiple species, it is currently unknown how each is used to control changes in trajectory. We addressed this problem by measuring body and wingbeat kinematics as hummingbirds tracked a revolving feeder, and estimating aerodynamic forces using a quasi-steady model. During arcing turns, hummingbirds symmetrically banked the stroke plane of both wings, and the body, into turns, supporting a body-dependent mechanism. However, several wingbeat asymmetries were present during turning, including a higher and flatter outer wingtip path and a lower more deviated inner wingtip path. A quasi-steady analysis of arcing turns performed with different trajectories revealed that changes in radius were associated with asymmetrical kinematics and forces, and changes in velocity were associated with symmetrical kinematics and forces. Collectively, our results indicate that both body-dependent and -independent force orientation mechanisms are available to hummingbirds, and that these kinematic strategies are used to meet the separate aerodynamic challenges posed by changes in velocity and turning radius. PMID:27030042

Left-right supersymmetry after the Higgs boson discovery

NASA Astrophysics Data System (ADS)

Frank, Mariana; Ghosh, Dilip Kumar; Huitu, Katri; Rai, Santosh Kumar; Saha, Ipsita; Waltari, Harri

2014-12-01

We perform a thorough analysis of the parameter space of the minimal left-right supersymmetric model in agreement with the LHC data. The model contains left- and right-handed fermionic doublets, two Higgs bidoublets, two Higgs triplet representations, and one singlet, insuring a charge-conserving vacuum. We impose the condition that the model complies with the experimental constraints on supersymmetric particles masses and on the doubly charged Higgs bosons and require that the parameter space of the model satisfies the LHC data on neutral Higgs signal strengths at 2 σ . We choose benchmark scenarios by fixing some basic parameters and scanning over the rest. The lightest supersymmetric particle in our scenarios is always the lightest neutralino. We find that the signals for H →γ γ and H →V V⋆ are correlated, while H →b b ¯ is anticorrelated with all of the other decay modes, and also that the contribution from singly charged scalars dominates that of the doubly charged scalars in H →γ γ and H →Z γ loops, contrary to type II seesaw models. We also illustrate the range for mass spectrum of the LRSUSY model in light of planned measurements of the branching ratio of H →γ γ to 10% level.

14. CONTROL PANELS, EAST SIDE, MAIN FLOOR: TO LEFT (ORIGINAL ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

14. CONTROL PANELS, EAST SIDE, MAIN FLOOR: TO LEFT (ORIGINAL EQUIPMENT): UPPER FOUR GLASS BOXES ARE OVERCURRENT PROTECTIVE RELAYS; MIDDLE FOUR GLASS BOXES CONTAIN TESTING SWITCHES; LOWER TWO BOXES ARE DG1 METERING CHART RECORDERS TO RIGHT (MODERN EQUIPMENT): UPPER FOUR BLACK BOXES ARE PROTECTIVE SERVICE RELAYS; MIDDLE FOUR BOXES CONTAIN TESTING SWITCHES; LARGE BOX BELOW HOUSES REMOTE METERING SYSTEM METAL CABINETS (LABELED L-2 & L-4) BELOW CONTAIN ORIGINAL POWER CIRCUIT BREAKERS - Bonneville Power Administration South Bank Substation, I-84, South of Bonneville Dam Powerhouse, Bonneville, Multnomah County, OR

Left endocarditis, changes in the new millennium.

PubMed

Noureddine-López, Mariam; de la Torre-Lima, Javier; Ruiz-Morales, Josefa; Gálvez-Acebal, Juan; Hidalgo-Tenorio, Carmen; de Alarcón González, César Arístides

2018-05-25

a description of infective left endocarditis at the turn of the millennium. A multicentre prospective study into the left endocarditis using data collected from the Andalusian cohort for the study of cardiovascular infections during 1984-2014. Of the 1,604 endocarditis cases collected, 382 belonged to G1 (group-1, period 1983-1999) and 1,222 to G2 (group-2, 2000-2014). Patients in the new millennium have a significantly higher mean age, have more comorbidity and concomitant diseases, and nosocomial and health-related endocarditis are more frequent, as well as complications. An increase in methicillin-resistant Staphylococcus aureus, Enterococcus sp., Gram-negative bacilli and Streptococcus bovis was noted. Regarding treatment, there is an increase in the use of cephalosporins and a decrease in penicillins; there is more surgery when admitted to hospital and less delay. Mortality stands at around 30% in both millennia. In the multivariate analysis, mortality was associated with: previous millennium (G1), age, Charlson index, renal failure and septic shock, and aetiologically with Staphylococcus aureus. Mortality remains stable, despite diagnostic and therapeutic improvements, because patients are older, have greater comorbidity, a closer relationship with the health care system (nosocomial) and microorganisms are more aggressive. Copyright © 2018 Elsevier España, S.L.U. All rights reserved.

Nodal signalling determines biradial asymmetry in Hydra.

PubMed

Watanabe, Hiroshi; Schmidt, Heiko A; Kuhn, Anne; Höger, Stefanie K; Kocagöz, Yigit; Laumann-Lipp, Nico; Ozbek, Suat; Holstein, Thomas W

2014-11-06

In bilaterians, three orthogonal body axes define the animal form, with distinct anterior-posterior, dorsal-ventral and left-right asymmetries. The key signalling factors are Wnt family proteins for the anterior-posterior axis, Bmp family proteins for the dorsal-ventral axis and Nodal for the left-right axis. Cnidarians, the sister group to bilaterians, are characterized by one oral-aboral body axis, which exhibits a distinct biradiality of unknown molecular nature. Here we analysed the biradial growth pattern in the radially symmetrical cnidarian polyp Hydra, and we report evidence of Nodal in a pre-bilaterian clade. We identified a Nodal-related gene (Ndr) in Hydra magnipapillata, and this gene is essential for setting up an axial asymmetry along the main body axis. This asymmetry defines a lateral signalling centre, inducing a new body axis of a budding polyp orthogonal to the mother polyp's axis. Ndr is expressed exclusively in the lateral bud anlage and induces Pitx, which encodes an evolutionarily conserved transcription factor that functions downstream of Nodal. Reminiscent of its function in vertebrates, Nodal acts downstream of β-Catenin signalling. Our data support an evolutionary scenario in which a 'core-signalling cassette' consisting of β-Catenin, Nodal and Pitx pre-dated the cnidarian-bilaterian split. We presume that this cassette was co-opted for various modes of axial patterning: for example, for lateral branching in cnidarians and left-right patterning in bilaterians.

LEFT WING AND FUSELAGE FROM THIRD LEVEL OF TAIL DOCK ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

LEFT WING AND FUSELAGE FROM THIRD LEVEL OF TAIL DOCK STAND. THE WING IS PREPARED FOR BASIC LUBRICATION WITH E SPOILER BOARDS UP AND ALL SAFETY LOCKS IN PLACE TO PROTECT MECHANICS FROM INJURY. ON THE WING AN INSPECTOR CHECKS THE ACTUATORS. - Greater Buffalo International Airport, Maintenance Hangar, Buffalo, Erie County, NY

New Vaccines Help Protect You

MedlinePlus

... Navigation Bar Home Current Issue Past Issues New Vaccines Help Protect You Past Issues / Fall 2006 Table ... this page please turn Javascript on. Important new vaccines have recently been approved for use and are ...

Children coordinate in a recurrent social dilemma by taking turns and along dominance asymmetries.

PubMed

Grueneisen, Sebastian; Tomasello, Michael

2017-02-01

Humans constantly have to coordinate their decisions with others even when their interests are conflicting (e.g., when 2 drivers have to decide who yields at an intersection). So far, however, little is known about the development of these abilities. Here, we present dyads of 5-year-olds (N = 40) with a repeated chicken game using a novel methodology: Two children each steered an automated toy train carrying a reward. The trains simultaneously moved toward each other so that in order to avoid a crash-which left both children empty-handed-1 train had to swerve. By swerving, however, the trains lost a portion of the rewards so that it was in each child's interest to go straight. Children coordinated their decisions successfully over multiple rounds, and they mostly did so by taking turns at swerving. In dyads in which turn-taking was rare, dominant children obtained significantly higher payoffs than their partners. Moreover, the coordination process was more efficient in turn-taking dyads as indicated by a significant reduction in conflicts and verbal protest. These findings indicate that already by the late preschool years children can independently coordinate decisions with peers in recurrent conflicts of interest. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Adaptive critic autopilot design of bank-to-turn missiles using fuzzy basis function networks.

PubMed

Lin, Chuan-Kai

2005-04-01

A new adaptive critic autopilot design for bank-to-turn missiles is presented. In this paper, the architecture of adaptive critic learning scheme contains a fuzzy-basis-function-network based associative search element (ASE), which is employed to approximate nonlinear and complex functions of bank-to-turn missiles, and an adaptive critic element (ACE) generating the reinforcement signal to tune the associative search element. In the design of the adaptive critic autopilot, the control law receives signals from a fixed gain controller, an ASE and an adaptive robust element, which can eliminate approximation errors and disturbances. Traditional adaptive critic reinforcement learning is the problem faced by an agent that must learn behavior through trial-and-error interactions with a dynamic environment, however, the proposed tuning algorithm can significantly shorten the learning time by online tuning all parameters of fuzzy basis functions and weights of ASE and ACE. Moreover, the weight updating law derived from the Lyapunov stability theory is capable of guaranteeing both tracking performance and stability. Computer simulation results confirm the effectiveness of the proposed adaptive critic autopilot.

49 CFR 218.29 - Alternate methods of protection.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false Alternate methods of protection. 218.29 Section....29 Alternate methods of protection. Instead of providing blue signal protection for workers in accordance with § 218.27, the following methods for blue signal protection may be used: (a) When workers are...

Relationship Between Head-Turn Gait Speed and Lateral Balance Function in Community-Dwelling Older Adults.

PubMed

Singh, Harshvardhan; Sanders, Ozell; McCombe Waller, Sandy; Bair, Woei-Nan; Beamer, Brock; Creath, Robert A; Rogers, Mark W

2017-10-01

To determine and compare gait speed during head-forward and side-to-side head-turn walking in individuals with lower versus greater lateral balance. Cross-sectional study. University research laboratory. Older adults (N=93; 42 men, 51 women; mean age ± SD, 73 ± 6.08y) who could walk independently. (1) Balance tolerance limit (BTL), defined as the lowest perturbation intensity where a multistep balance recovery pattern was first evoked in response to randomized lateral waist-pull perturbations of standing balance to the left and right sides, at 6 different intensities (range from level 2: 4.5-cm displacement at 180cm/s 2 acceleration, to level 7: 22.5-cm displacement at 900cm/s 2 acceleration); (2) gait speed, determined using an instrumented gait mat; (3) balance, evaluated with the Activities-specific Balance Confidence Scale; and (4) mobility, determined with the Timed Up and Go (TUG). Individuals with low versus high BTL had a slower self-selected head-forward gait speed and head-turn gait speed (P=.002 and P<.001, respectively); the magnitude of difference was greater in head-turn gait speed than head-forward gait speed (Cohen's d=1.0 vs 0.6). Head-turn gait speed best predicted BTL. BTL was moderately and positively related (P=.003) to the ABC Scale and negatively related (P=.017) to TUG. Head-turn gait speed is affected to a greater extent than head-forward gait speed in older individuals with poorer lateral balance and at greater risk of falls. Moreover, head-turn gait speed can be used to assess the interactions of limitations in lateral balance function and gait speed in relation to fall risk in older adults. Copyright © 2017 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Realistic page-turning of electronic books

NASA Astrophysics Data System (ADS)

Fan, Chaoran; Li, Haisheng; Bai, Yannan

2014-01-01

The booming electronic books (e-books), as an extension to the paper book, are popular with readers. Recently, many efforts are put into the realistic page-turning simulation o f e-book to improve its reading experience. This paper presents a new 3D page-turning simulation approach, which employs piecewise time-dependent cylindrical surfaces to describe the turning page and constructs smooth transition method between time-dependent cylinders. The page-turning animation is produced by sequentially mapping the turning page into the cylinders with different radii and positions. Compared to the previous approaches, our method is able to imitate various effects efficiently and obtains more natural animation of turning page.

The Molecular Differentiation of Anatomically Paired Left and Right Mantles of the Pacific Oyster Crassostrea gigas.

PubMed

Wei, Lei; Xu, Fei; Wang, Yuzhi; Cai, Zhongqiang; Yu, Wenchao; He, Cheng; Jiang, Qiuyun; Xu, Xiqiang; Guo, Wen; Wang, Xiaotong

2018-03-28

Left-right (L-R) asymmetry is controlled by gene regulation pathways for the L-R axis, and in vertebrates, the gene Pitx2 in TGF-β signaling pathway plays important roles in the asymmetrical formation of organs. However, less is known about the asymmetries of anatomically identical paired organs, as well as the transcriptional regulation mechanism of the gene Pitx in invertebrates. Here, we report the molecular biological differences between the left and right mantles of an invertebrate, the Pacific oyster Crassostrea gigas, and propose one possible mechanism underlying those differences. RNA sequencing (RNA-seq) analysis indicated that the paired organs showed different gene expression patterns, suggesting possible functional differences in shell formation, pheromone signaling, nerve conduction, the stress response, and other physiological processes. RNA-seq and real-time qPCR analysis indicated high right-side expression of the Pitx homolog (cgPitx) in oyster mantle, supporting a conserved role for Pitx in controlling asymmetry. Methylation-dependent restriction-site associated DNA sequencing (MethylRAD) identified a methylation site in the promoter region of cgPitx and showed significantly different methylation levels between the left and right mantles. This is the first report, to our knowledge, of such a difference in methylation in spiralians, and it was further confirmed in 18 other individuals by using a pyrosequencing assay. The miRNome analysis and the TGF-β receptor/Smad inhibition experiment further supported that several genes in TGF-β signaling pathway may be related with the L/R asymmetry of oyster mantles. These results suggested that the molecular differentiation of the oyster's paired left and right mantles is significant, TGF-β signaling pathway could be involved in establishing or maintaining the asymmetry, and the cgPitx gene as one of genes in this pathway; the different methylation levels in its promoter regions between L/R mantles was

Self-configurable radio receiver system and method for use with signals without prior knowledge of signal defining characteristics

NASA Technical Reports Server (NTRS)

Hamkins, Jon (Inventor); Simon, Marvin K. (Inventor); Divsalar, Dariush (Inventor); Dolinar, Samuel J. (Inventor); Tkacenko, Andre (Inventor)

2013-01-01

A method, radio receiver, and system to autonomously receive and decode a plurality of signals having a variety of signal types without a priori knowledge of the defining characteristics of the signals is disclosed. The radio receiver is capable of receiving a signal of an unknown signal type and, by estimating one or more defining characteristics of the signal, determine the type of signal. The estimated defining characteristic(s) is/are utilized to enable the receiver to determine other defining characteristics. This in turn, enables the receiver, through multiple iterations, to make a maximum-likelihood (ML) estimate for each of the defining characteristics. After the type of signal is determined by its defining characteristics, the receiver selects an appropriate decoder from a plurality of decoders to decode the signal.

Permutation Entropy and Signal Energy Increase the Accuracy of Neuropathic Change Detection in Needle EMG

PubMed Central

2018-01-01

Background and Objective. Needle electromyography can be used to detect the number of changes and morphological changes in motor unit potentials of patients with axonal neuropathy. General mathematical methods of pattern recognition and signal analysis were applied to recognize neuropathic changes. This study validates the possibility of extending and refining turns-amplitude analysis using permutation entropy and signal energy. Methods. In this study, we examined needle electromyography in 40 neuropathic individuals and 40 controls. The number of turns, amplitude between turns, signal energy, and “permutation entropy” were used as features for support vector machine classification. Results. The obtained results proved the superior classification performance of the combinations of all of the above-mentioned features compared to the combinations of fewer features. The lowest accuracy from the tested combinations of features had peak-ratio analysis. Conclusion. Using the combination of permutation entropy with signal energy, number of turns and mean amplitude in SVM classification can be used to refine the diagnosis of polyneuropathies examined by needle electromyography. PMID:29606959

Wnt/PCP Instructions for Cilia in Left-Right Asymmetry.

PubMed

Wu, Jun; Mlodzik, Marek

2017-03-13

Wnt-Frizzled/planar cell polarity (PCP) signaling establishes cell orientation within the epithelial plane, but whether Wnts are instructive or permissive is debated. Reporting in Developmental Cell, Minegishi et al. (2017) uncover an instructive link from Wnt5a/b gradients to PCP-factor-regulated polarized cilia positioning that is essential to mouse embryo left-right asymmetry establishment. Copyright © 2017. Published by Elsevier Inc.

Analysis of acoustic emission signals and monitoring of machining processes

PubMed

Govekar; Gradisek; Grabec

2000-03-01

Monitoring of a machining process on the basis of sensor signals requires a selection of informative inputs in order to reliably characterize and model the process. In this article, a system for selection of informative characteristics from signals of multiple sensors is presented. For signal analysis, methods of spectral analysis and methods of nonlinear time series analysis are used. With the aim of modeling relationships between signal characteristics and the corresponding process state, an adaptive empirical modeler is applied. The application of the system is demonstrated by characterization of different parameters defining the states of a turning machining process, such as: chip form, tool wear, and onset of chatter vibration. The results show that, in spite of the complexity of the turning process, the state of the process can be well characterized by just a few proper characteristics extracted from a representative sensor signal. The process characterization can be further improved by joining characteristics from multiple sensors and by application of chaotic characteristics.

Inhibitor of apoptosis signal-regulating kinase 1 protects against acetaminophen-induced liver injury

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

Xie, Yuchao; Ramachandran, Anup; Breckenridge, David G.

Metabolic activation and oxidant stress are key events in the pathophysiology of acetaminophen (APAP) hepatotoxicity. The initial mitochondrial oxidative stress triggered by protein adduct formation is amplified by c-jun-N-terminal kinase (JNK), resulting in mitochondrial dysfunction and ultimately cell necrosis. Apoptosis signal-regulating kinase 1 (ASK1) is considered the link between oxidant stress and JNK activation. The objective of the current study was to assess the efficacy and mechanism of action of the small-molecule ASK1 inhibitor GS-459679 in a murine model of APAP hepatotoxicity. APAP (300 mg/kg) caused extensive glutathione depletion, JNK activation and translocation to the mitochondria, oxidant stress and livermore » injury as indicated by plasma ALT activities and area of necrosis over a 24 h observation period. Pretreatment with 30 mg/kg of GS-459679 almost completely prevented JNK activation, oxidant stress and injury without affecting the metabolic activation of APAP. To evaluate the therapeutic potential of GS-459679, mice were treated with APAP and then with the inhibitor. Given 1.5 h after APAP, GS-459679 was still protective, which was paralleled by reduced JNK activation and p-JNK translocation to mitochondria. However, GS-459679 treatment was not more effective than N-acetylcysteine, and the combination of GS-459679 and N-acetylcysteine exhibited similar efficacy as N-acetylcysteine monotherapy, suggesting that GS-459769 and N-acetylcysteine affect the same pathway. Importantly, inhibition of ASK1 did not impair liver regeneration as indicated by PCNA staining. In conclusion, the ASK1 inhibitor GS-459679 protected against APAP toxicity by attenuating JNK activation and oxidant stress in mice and may have therapeutic potential for APAP overdose patients. - Highlights: • Two ASK1 inhibitors protected against acetaminophen-induced liver injury. • The ASK1 inhibitors protect when used as pre- or post-treatment. • Protection by ASK1

Leptin signaling protects the gut from Entamoeba histolytica infection.

PubMed

Vedantam, Gayatri; Viswanathan, V K

2012-01-01

The role of the adipose-derived hormone leptin, and leptin receptors, in signaling satiety to the central nervous system and regulating energy balance is well recognized. But leptin also acts on peripheral tissues such as skeletal muscles, adipose tissues, pancreas, liver, intestine and the immune system. The existence of different splice variants of leptin receptor and the numerous intracellular signaling pathways triggered by leptin make this a truly versatile system. Two recent studies explore the link between malnutrition, leptin signaling and susceptibility to amebic infection. These studies point to important and novel aspects of leptin signaling in maintaining gut homeostasis and warding off infections.

Left-sided congenital heart lesions in mosaic Turner syndrome.

PubMed

Bouayed Abdelmoula, Nouha; Abdelmoula, Balkiss; Smaoui, Walid; Trabelsi, Imen; Louati, Rim; Aloulou, Samir; Aloulou, Wafa; Abid, Fatma; Kammoun, Senda; Trigui, Khaled; Bedoui, Olfa; Denguir, Hichem; Mallek, Souad; Ben Aziza, Mustapha; Dammak, Jamila; Kaabi, Oldez; Abdellaoui, Nawel; Turki, Fatma; Kaabi, Asma; Kamoun, Wafa; Jabeur, Jihen; Ltaif, Wided; Chaker, Kays; Fourati, Haytham; M'rabet, Samir; Ben Ameur, Hedi; Gouia, Naourez; Mhiri, Mohamed Nabil; Rebai, Tarek

2018-04-01

In the era of the diseasomes and interactome networks, linking genetics with phenotypic traits in Turner syndrome should be studied thoroughly. As a part of this stratagem, mosaicism of both X and Y chromosome which is a common finding in TS and an evaluation of congenital heart diseases in the different situations of mosaic TS types, can be helpful in the identification of disturbed sex chromosomes, genes and signaling pathway actors. Here we report the case of a mosaic TS associated to four left-sided CHD, including BAV, COA, aortic aneurysms and dissections at an early age. The mosaicism included two cell lines, well-defined at the cytogenetic and molecular levels: a cell line which is monosomic for Xp and Xq genes (45,X) and another which is trisomic for pseudoautosomal genes that are present on the X and Y chromosomes and escape X inactivation: 45,X[8]/46,X,idic(Y)(pter→q11.2::q11.2→pter)[42]. This case generates two hypotheses about the contribution of genes linked to the sex chromosomes and the signaling pathways involving these genes, in left-sided heart diseases. The first hypothesis suggests the interaction between X chromosome and autosomal genes or loci of aortic development, possibly dose-dependent, and which could be in the framework of TGF-β-SMAD signaling pathways. The second implies that left-sided congenital heart lesions involve sex chromosomes loci. The reduced dosage of X chromosome gene(s), escaping X inactivation during development, contributes to this type of CHD. Regarding our case, these X chromosome genes may have homologues at the Y chromosome, but the process of inactivation of the centromeres of the isodicentric Y spreads to the concerned Y chromosome genes. Therefore, this case emerges as an invitation to consider the mosaics of Turner syndrome and to study their phenotypes in correlation with their genotypes to discover the underlying developmental and genetic mechanisms, especially the ones related to sex chromosomes.

Laterotopic representation of left-right information onto the dorso-ventral axis of a zebrafish midbrain target nucleus.

PubMed

Aizawa, Hidenori; Bianco, Isaac H; Hamaoka, Takanori; Miyashita, Toshio; Uemura, Osamu; Concha, Miguel L; Russell, Claire; Wilson, Stephen W; Okamoto, Hitoshi

2005-02-08

The habenulae are part of an evolutionarily highly conserved limbic-system conduction pathway that connects telencephalic nuclei to the interpeduncular nucleus (IPN) of the midbrain . In zebrafish, unilateral activation of the Nodal signaling pathway in the left brain specifies the laterality of the asymmetry of habenular size . We show "laterotopy" in the habenulo-interpeduncular projection in zebrafish, i.e., the stereotypic, topographic projection of left-sided habenular axons to the dorsal region of the IPN and of right-sided habenular axons to the ventral IPN. This asymmetric projection is accounted for by a prominent left-right (LR) difference in the size ratio of the medial and lateral habenular sub-nuclei, each of which specifically projects either to ventral or dorsal IPN targets. Asymmetric Nodal signaling directs the orientation of laterotopy but is dispensable for the establishment of laterotopy itself. Our results reveal a mechanism by which information distributed between left and right sides of the brain can be transmitted bilaterally without loss of LR coding, which may play a crucial role in functional lateralization of the vertebrate brain .

Driving simulator study of J-Turn acceleration/deceleration lane and U-turn spacing.

DOT National Transportation Integrated Search

2016-11-01

Carlos Sun : http://orcid.org/0000-0002-8857-9648 : The J-turn, also known as RCUT (Restricted Crossing U-Turn) and Superstreet, is an innovative geometric design that can improve intersection safety. Even though this design has been in use in severa...

The turn-of-the-century drought in North America: The new normal?

NASA Astrophysics Data System (ADS)

Schwalm, C. R.; Williams, C. A.; Schaefer, K. M.; NACP Site Synthesis Team

2011-12-01

At the turn of the century, from 2000 to 2004, western North America (25°-50°N, 100°-125°W) experienced a severe drought with far reaching consequences for the terrestrial biosphere. We quantified the drought's water and carbon cycle implications using upscaled flux tower data, observed and simulated fluxes from the NACP Site Synthesis, remote sensing products, weather reanalysis, crop yield, and river discharge. During the turn of the century drought we found a widespread drydown of the terrestrial biosphere, large decreases in river discharge and greenness, and a ~10% loss in cropland productivity. At the footprint scale carbon uptake declined with an anomalous carbon source of 0.11 Pg C/yr integrated over the full domain. Flux towers also recorded a clear signal of reduced latent and increased sensible heat fluxes, apart from grasslands. Dendrochronological reconstructions of drought extent, duration, and severity, based on the Palmer Drought Severity Index drought metric, indicated that the turn of the century drought was unprecedented since 1200 CE. Predicted changes in precipitation and drought, based on the CMIP3 multi-model mean, could permanently disable the weak sink (NEE = -0.19 Pg C/yr) in western North America by the midpoint of the 21st Century. Projections indicate the turn-of-the-century drought will be wet compared to the latter half of the 21st Century.

Berberine inhibits macrophage M1 polarization via AKT1/SOCS1/NF-κB signaling pathway to protect against DSS-induced colitis.

PubMed

Liu, Yunxin; Liu, Xiang; Hua, Weiwei; Wei, Qingyan; Fang, Xianjun; Zhao, Zheng; Ge, Chun; Liu, Chao; Chen, Chen; Tao, Yifu; Zhu, Yubing

2018-04-01

Berberine has been reported to have protective effects in colitis treatment. However, the detailed mechanisms remain unclear. Herein, we demonstrated that berberine could protect against dextran sulfate sodium (DSS)-induced colitis in mice by regulating macrophage polarization. In the colitis mouse model, berberine ameliorated DSS-induced colon shortening and colon tissue injury. Moreover, berberine-treated mice showed significant reduction in the disease activity index (DAI), pro-inflammatory cytokines expression and macrophages infiltration compared with the DSS-treated mice. Notably, berberine significantly reduced the percentage of M1 macrophages. In vitro analysis also confirmed the inhibitory effects of berberine on macrophages M1 polarization in RAW267.4 cells. Further investigation showed that berberine promoted AKT1 expression in mRNA and protein level. Silence of AKT1 abolished the inhibitory effect of berberine on macrophages M1 polarization. The berberine-induced AKT1 expression promoted suppressers of cytokine signaling (SOCS1) activation, which inhibited nuclear factor-kappa B (NF-κB) phosphorylation. In addition, we also found that berberine activated AKT1/SOCS1 signaling pathway but inhibited p65 phosphorylation in macrophages in vivo. Therefore, we concluded that berberine played a regulatory role in macrophages M1 polarization in DSS-induced colitis via AKT1/SOCS1/NF-κB signaling pathway. This unexpected property of berberine may provide a potential explanation for its protective effects in colitis treatment. Copyright © 2018 Elsevier B.V. All rights reserved.

Abdominal aortic aneurysm with aorta-left renal vein fistula with left varicocele.

PubMed

Meyerson, S L; Haider, S A; Gupta, N; O'Dorsio, J E; McKinsey, J F; Schwartz, L B

2000-04-01

Abdominal aortic aneurysm with spontaneous aorto-left renal vein fistula is a rare but well-described clinical entity usually with abdominal pain, hematuria, and a nonfunctioning left kidney. This report describes a 44-year-old man with left-sided groin pain and varicocele who was treated with conservative measures only. The diagnosis was eventually made when he returned with microscopic hematuria, elevated serum creatinine level, and nonfunction of the left kidney; computed tomography scan demonstrated a 6-cm abdominal aortic aneurysm, a retroaortic left renal vein, and an enlargement of the left kidney. This patient represents the youngest to be reported with aorto-left renal vein fistula and the second case with a left-sided varicocele.

Turn Basin Construction

NASA Image and Video Library

2017-06-30

At NASA's Kennedy Space Center in Florida, cement is poured as part of a construction project to upgrade the turn basin wharf. The work includes driving multiple precast concrete piles to a depth of about 70 feet to accommodate arrival of the core stage for the agency's Space Launch System (SLS) rocket. When the stage for NASA's SLS departs the Michoud Assembly Facility in New Orleans, it will be shipped by the agency's modified barge to the Launch Complex 39 turn basin.

Right-to-left shunt detection sensitivity with air-saline and air-succinil gelatin transcranial Doppler.

PubMed

Puledda, Francesca; Toscano, Massimiliano; Pieroni, Alessio; Veneroso, Gabriele; Di Piero, Vittorio; Vicenzini, Edoardo

2016-02-01

Air-saline transcranial Doppler is nowadays the first-choice examination to identify right-to-left shunt. To increase right-to-left shunt detection in echocardiography, cardiologists also use air-gelatin mixtures, which are more stable, more echogenic, and easier to be prepared. We assessed the sensitivity of air-gelatin compared with air-saline for transcranial Doppler right-to-left shunt detection. Air-saline transcranial Doppler, during unilateral middle cerebral artery monitoring at rest and after Valsalva maneuver, was performed in patients referred to our neurosonology laboratory for right-to-left shunt detection. The same transcranial Doppler protocol was repeated with air-gelatin. To consider transcranial Doppler positive for cardiac right-to-left shunt, at least one embolic signal had to be detected within 20″ from contrast injection. Later signals were interpreted of pulmonary origin. Trans-thoracic echocardiography was repeated with both air-saline and air-gelatin. A total of 97 patients were enrolled; 46 had negative transcranial Doppler for cardiac right-to-left shunt with both air-saline and air-gelatin; out of these, four patients with air-saline plus two more patients with air-gelatin presented late, isolated microemboli, slightly more numerous with air-gelatin: these were interpreted as pulmonary shunts and confirmed with trans-thoracic echocardiography. In 28 patients with already early positive air-saline transcranial Doppler at rest, air-gelatin induced a marked right-to-left shunt increase, facilitating its visualization at trans-thoracic echocardiography. In 23 patients in whom air-saline transcranial Doppler was negative at rest and positive for cardiac right-to-left shunt only after Valsalva maneuver, air-gelatin was able to reveal shunt also at rest. Air-gelatin increases right-to-left shunt detection sensitivity with transcranial Doppler in particular at rest, even in patients in whom air-saline mixture fails to identify the shunt. The

Construction at Turn Basin

NASA Image and Video Library

2017-06-14

Modifications are underway at the Launch Complex 39 turn basin wharf at NASA's Kennedy Space Center in Florida to prepare for the arrival of the agency's massive Space Launch System (SLS) core stage aboard the barge Pegasus. Precast concrete poles are being driven to a depth of about 70 feet into the bedrock below the water around the turn basin; later filled with concrete. The upgrades are necessary to accommodate the increased weight of the core stage along with ground support and transportation equipment aboard the modified barge Pegasus. The Ground Systems Development and Operations Program is overseeing the upgrades to the turn basin wharf.

Does serotonin-modulating anticonsolidation protein (SMAP) influence the choice of turning direction in carps, Cyprinus carpio, in a T-maze?

PubMed

Garina, D V; Nepomnyashchikh, V A; Mekhtiev, A A

2016-08-01

Serotonin-modulating anticonsolidation protein (SMAP) can impair the formation of memory traces in mammals and fish. We have studied the influence of SMAP on behavioral lateralization of juvenile carps Cyprinus carpio in a T-maze without food reinforcement in three experimental groups (n = 8 each): (1) negative control (intact animals); (2) experimental group (fish injected ICV with SMAP; 2 μl, 1.2 mg ml(-1)) and (3) active control group (fish injected ICV with inactivated SMAP). The behavioral lateralization of carps was observed on the 1st, 2nd, 3rd and 6th days after the injections. In each observation session, a fish was placed five times in a start chamber of the T-maze. The direction of the turn upon leaving the start chamber, as well as the latency from the opening of start chamber flap to the fish's turn was registered. The number of right turns (of all five turns observed during the session) was a criterion of lateralization. It was found that carps have no inherent preference for turning left or right. The SMAP injection did not influence the choice of turning direction, but increases latency values insignificantly. The results are important for the correct interpretation and clarification of data reporting the role of SMAP in training and formation of spatial memory of fish in a maze.

Protective effect of Ginkgo biloba leaves extract, EGb761, on myocardium injury in ischemia reperfusion rats via regulation of TLR-4/NF-κB signaling pathway.

PubMed

Tang, Yuping; Zhou, Guisheng; Yao, Lijun; Xue, Ping; Yu, Danhong; Xu, Renjie; Shi, Wen; Yao, Xin; Yan, Zhaowei; Duan, Jin-Ao

2017-10-17

Beneficial actions of EGb 761 against ischemia/reperfusion (I/R) injury in lung, brain and renal ischemia have been described. However, the relationship between EGb 761 and signal molecules in myocardial ischemia reperfusion has not been well elucidated. In this study, we investigated the effects and mechanism of EGb 761 preconditioning on anti-myocardial I/R injuries in vivo . Meanwhile, their potential anti-oxidative stress and anti-inflammation effect were assessed. Hemodynamic parameters were monitored as left ventricular systolic pressure, LV end-diastolic pressure and maximal rate of increase and decrease of left ventricular pressure (dP/dtmax). The oxidative stress indicators and inflammatory factors were also evaluated. Western blot method was used for analysis of toll-like receptor 4 (TLR4), p-TLR4, nuclear factor-κB (NF-κB), p-NF-κB p65, Bax and Bcl-2 protein expressions. EGb 761 significantly improved cardiac function, decreased levels of creatine kinase, aspartate aminotransferase and lactate dehydrogenase. EGb 761 also restrained the oxidative stress related to myocardial ischemia injury as evidenced by decreased malondialdehyde, superoxide dismutase, catalase, glutathione-peroxidase, glutathione reductase activity. Meanwhile, the inflammatory cascade was inhibited as evidenced by decreased cytokines such as tumor necrosis factor-α, interleukin-6 and interleukin-1β. Our results still showed that EGb 761 pretreatment significantly decrease the level of cleaved Bax, and increase the level of Bcl-2 in rats subjected to I/R injury. Simultaneously, the expressions of myocardial TLR4 and NF-κB were significantly decreased. It can be concluded that EGb 761 pretreatment was protected against myocardium I/R injury by decreasing oxidative stress, repressing inflammatory cascade in vivo and inhibiting TLR4/NF-κB pathway.

Eucalyptus globulus extract protects against UVB-induced photoaging by enhancing collagen synthesis via regulation of TGF-β/Smad signals and attenuation of AP-1.

PubMed

Park, Bom; Hwang, Eunson; Seo, Seul A; Cho, Jin-Gyeong; Yang, Jung-Eun; Yi, Tae-Hoo

2018-01-01

UV irradiation triggers the overproduction of matrix metalloproteinases and collagen degradation, which in turn causes increased pigmentation, dryness, and deep wrinkling of the skin. These chronic symptoms are collectively referred to as photoaging. Eucalyptus globulus is an evergreen tree that is widely used in cosmetics because of its antimicrobial activity. In this study, we investigated the protective effect of 50% ethanol extracts of Eucalyptus globulus on UV-induced photoaging in vitro and in vivo. Normal human dermal fibroblasts were treated with Eucalyptus globulus at concentrations ranging from 1 to 100 μg/mL after UVB or non-UVB irradiation. We found that Eucalyptus globulus suppressed the expression of MMPs and IL-6, but increased the expression of TGF-β1 and procollagen type 1. In addition, Eucalyptus globulus inhibited activation of the AP-1 transcription factor, an inducer of MMPs. Eucalyptus globulus was also found to regulate TGF-β/Smad signaling by reversing the activity of negative Smad regulators. Lastly, in vivo studies showed that topical application of Eucalyptus globulus on UVB-irradiated hairless mice reduced wrinkle formation and dryness by down-regulating MMP-1 and up-regulating expression of elastin, TGF-β1, and procollagen type 1. Taken together, these data suggest that Eucalyptus globulus may be a useful agent in cosmetic products. Copyright © 2017 Elsevier Inc. All rights reserved.

Pellino-1 Protects Periodontal Ligament Stem Cells Against H2O2-Induced Apoptosis via Activation of NF-κB Signaling.

PubMed

Tian, Jiangang; Gu, Liufang; Adams, Andrew; Wang, Xueliang; Huang, Ruizhe

2018-06-02

To determine the protective effects of Pellino-1 against H 2 O 2 -induced apoptosis in periodontal ligament stem cells (PDLSC). We demonstrated that H 2 O 2 decreases PDLSC viability by 40 and 50% with the concentrations of 400 and 500 μM, respectively, with an observed downregulation of Pellino-1 mRNA and protein; we further concluded that overexpression of Pellino-1 significantly lowers 8-hydroxy-2'-deoxyguanosine levels by 10% and upregulates superoxide dismutase 1, glutathione peroxidase levels, and catalase mRNA levels by 200, 40, and 250%, respectively. More importantly, we found that overexpression of Pellino-1 inhibited H 2 O 2 -induced cellular apoptosis through the activation of the NF-κB signaling pathway. Pellino-1 may be critically important for cell survival in the presence of oxidative elements; activation of the NF-κB signaling cascade was required for the overexpression of Pellino-1 to protect the cells from H 2 O 2 -induced apoptosis.

14 CFR 417.209 - Malfunction turn analysis.

Code of Federal Regulations, 2013 CFR

2013-01-01

... turn behavior for each cause of a malfunction turn. For each malfunction turn envelope, the analysis... 14 Aeronautics and Space 4 2013-01-01 2013-01-01 false Malfunction turn analysis. 417.209 Section..., DEPARTMENT OF TRANSPORTATION LICENSING LAUNCH SAFETY Flight Safety Analysis § 417.209 Malfunction turn...

14 CFR 417.209 - Malfunction turn analysis.

Code of Federal Regulations, 2012 CFR

2012-01-01

... turn behavior for each cause of a malfunction turn. For each malfunction turn envelope, the analysis... 14 Aeronautics and Space 4 2012-01-01 2012-01-01 false Malfunction turn analysis. 417.209 Section..., DEPARTMENT OF TRANSPORTATION LICENSING LAUNCH SAFETY Flight Safety Analysis § 417.209 Malfunction turn...

14 CFR 417.209 - Malfunction turn analysis.

Code of Federal Regulations, 2014 CFR

2014-01-01

... turn behavior for each cause of a malfunction turn. For each malfunction turn envelope, the analysis... 14 Aeronautics and Space 4 2014-01-01 2014-01-01 false Malfunction turn analysis. 417.209 Section..., DEPARTMENT OF TRANSPORTATION LICENSING LAUNCH SAFETY Flight Safety Analysis § 417.209 Malfunction turn...

Activation of PPARδ signaling improves skeletal muscle oxidative metabolism and endurance function in an animal model of ischemic left ventricular dysfunction

PubMed Central

Zizola, Cynthia; Kennel, Peter J.; Akashi, Hirokazu; Ji, Ruiping; Castillero, Estibaliz; George, Isaac; Homma, Shunichi

2015-01-01

Exercise intolerance in heart failure has been linked to impaired skeletal muscle oxidative capacity. Oxidative metabolism and exercise capacity are regulated by PPARδ signaling. We hypothesized that PPARδ stimulation reverts skeletal muscle oxidative dysfunction. Myocardial infarction (MI) was induced in C57BL/6 mice and the development of ventricular dysfunction was monitored over 8 wk. Mice were randomized to the PPARδ agonist GW501516 (5 mg/kg body wt per day for 4 wk) or placebo 8 wk post-MI. Muscle function was assessed through running tests and grip strength measurements. In muscle, we analyzed muscle fiber cross-sectional area and fiber types, metabolic gene expression, fatty acid (FA) oxidation and ATP content. Signaling pathways were studied in C2C12 myotubes. FA oxidation and ATP levels decreased in muscle from MI mice compared with sham- operated mice. GW501516 administration increased oleic acid oxidation levels in skeletal muscle of the treated MI group compared with placebo treatment. This was accompanied by transcriptional changes including increased CPT1 expression. Further, the PPARδ-agonist improved running endurance compared with placebo. Cell culture experiments revealed protective effects of GW501516 against the cytokine-induced decrease of FA oxidation and changes in metabolic gene expression. Skeletal muscle dysfunction in HF is associated with impaired PPARδ signaling and treatment with the PPARδ agonist GW501516 corrects oxidative capacity and FA metabolism and improves exercise capacity in mice with LV dysfunction. Pharmacological activation of PPARδ signaling could be an attractive therapeutic intervention to counteract the progressive skeletal muscle dysfunction in HF. PMID:25713305

Left-right asymmetry in the level of active Nodal protein produced in the node is translated into left-right asymmetry in the lateral plate of mouse embryos.

PubMed

Kawasumi, Aiko; Nakamura, Tetsuya; Iwai, Naomi; Yashiro, Kenta; Saijoh, Yukio; Belo, Jose Antonio; Shiratori, Hidetaka; Hamada, Hiroshi

2011-05-15

Left-right (L-R) asymmetry in the mouse embryo is generated in the node and is dependent on cilia-driven fluid flow, but how the initial asymmetry is transmitted from the node to the lateral plate has remained unknown. We have now identified a transcriptional enhancer (ANE) in the human LEFTY1 gene that exhibits marked L>R asymmetric activity in perinodal cells of the mouse embryo. Dissection of ANE revealed that it is activated in the perinodal cells on the left side by Nodal signaling, suggesting that Nodal activity in the node is asymmetric at a time when Nodal expression is symmetric. Phosphorylated Smad2/3 (pSmad2) indeed manifested an L-R asymmetric distribution at the node, being detected in perinodal cells preferentially on the left side. This asymmetry in pSmad2 distribution was found to be generated not by unidirectional transport of Nodal but rather as a result of Lsignaling in perinodal cells is dispensable for L-R patterning of LPM, given that its inhibition by expression of dominant negative forms of Smad3 or ALK4 was still associated with normal (left-sided) Nodal expression in LPM. Our results suggest that LPM is the direct target of Nodal secreted by the perinodal cells, and that an L>R distribution of active Nodal in the node is translated into the asymmetry in LPM. Copyright © 2011 Elsevier Inc. All rights reserved.

Dexamethasone protects auditory hair cells against TNFalpha-initiated apoptosis via activation of PI3K/Akt and NFkappaB signaling.

PubMed

Haake, Scott M; Dinh, Christine T; Chen, Shibing; Eshraghi, Adrien A; Van De Water, Thomas R

2009-09-01

Tumor necrosis factor alpha (TNFalpha) is associated with trauma-induced hearing loss. Local treatment of cochleae of trauma-exposed animals with a glucocorticoid is effective in reducing the level of hearing loss that occurs post-trauma (e.g., electrode insertion trauma-induced hearing loss/dexamethasone treatment). Dexamethasone (Dex) protects auditory hair cells (AHCs) from trauma-induced loss by activating cellular signal pathways that promote cell survival. Organ of Corti explants challenged with an ototoxic level of TNFalpha was the trauma model with Dex the otoprotective drug. A series of inhibitors were used in combination with the Dex treatment of TNFalpha-exposed explants to investigate the signal molecules that participate in Dex-mediated otoprotection. The otoprotective capacity of Dex against TNFalpha ototoxicity was determined by hair cell counts obtained from fixed explants stained with FITC-phalloidin labeling with investigators blinded to specimen identity. The general caspase inhibitor Boc-d-fmk prevented TNFalpha-induced AHC death. There was a significant reduction (p<0.05) in the efficacy of Dex otoprotection against TNFalpha ototoxicity when the following cellular events were blocked: (1) glucocorticoid receptors (Mif); (2) PI3K (LY294002); (3) Akt/PKB (SH-6); and (4) NFkappaB (NFkappaB-I). Dex treatment protects hair cells against TNFalpha apoptosis in vitro by activation of PI3K/Akt and NFkappaB signaling.

Controlling a human-computer interface system with a novel classification method that uses electrooculography signals.

PubMed

Wu, Shang-Lin; Liao, Lun-De; Lu, Shao-Wei; Jiang, Wei-Ling; Chen, Shi-An; Lin, Chin-Teng

2013-08-01

Electrooculography (EOG) signals can be used to control human-computer interface (HCI) systems, if properly classified. The ability to measure and process these signals may help HCI users to overcome many of the physical limitations and inconveniences in daily life. However, there are currently no effective multidirectional classification methods for monitoring eye movements. Here, we describe a classification method used in a wireless EOG-based HCI device for detecting eye movements in eight directions. This device includes wireless EOG signal acquisition components, wet electrodes and an EOG signal classification algorithm. The EOG classification algorithm is based on extracting features from the electrical signals corresponding to eight directions of eye movement (up, down, left, right, up-left, down-left, up-right, and down-right) and blinking. The recognition and processing of these eight different features were achieved in real-life conditions, demonstrating that this device can reliably measure the features of EOG signals. This system and its classification procedure provide an effective method for identifying eye movements. Additionally, it may be applied to study eye functions in real-life conditions in the near future.

NetTurnP--neural network prediction of beta-turns by use of evolutionary information and predicted protein sequence features.

PubMed

Petersen, Bent; Lundegaard, Claus; Petersen, Thomas Nordahl

2010-11-30

β-turns are the most common type of non-repetitive structures, and constitute on average 25% of the amino acids in proteins. The formation of β-turns plays an important role in protein folding, protein stability and molecular recognition processes. In this work we present the neural network method NetTurnP, for prediction of two-class β-turns and prediction of the individual β-turn types, by use of evolutionary information and predicted protein sequence features. It has been evaluated against a commonly used dataset BT426, and achieves a Matthews correlation coefficient of 0.50, which is the highest reported performance on a two-class prediction of β-turn and not-β-turn. Furthermore NetTurnP shows improved performance on some of the specific β-turn types. In the present work, neural network methods have been trained to predict β-turn or not and individual β-turn types from the primary amino acid sequence. The individual β-turn types I, I', II, II', VIII, VIa1, VIa2, VIba and IV have been predicted based on classifications by PROMOTIF, and the two-class prediction of β-turn or not is a superset comprised of all β-turn types. The performance is evaluated using a golden set of non-homologous sequences known as BT426. Our two-class prediction method achieves a performance of: MCC=0.50, Qtotal=82.1%, sensitivity=75.6%, PPV=68.8% and AUC=0.864. We have compared our performance to eleven other prediction methods that obtain Matthews correlation coefficients in the range of 0.17-0.47. For the type specific β-turn predictions, only type I and II can be predicted with reasonable Matthews correlation coefficients, where we obtain performance values of 0.36 and 0.31, respectively. The NetTurnP method has been implemented as a webserver, which is freely available at http://www.cbs.dtu.dk/services/NetTurnP/. NetTurnP is the only available webserver that allows submission of multiple sequences.

Intraoperative left subclavian artery occlusion with left hand ischaemia and steal syndrome in the left internal thoracic artery

PubMed Central

Jelenc, Matija; Kneževič, Ivan; Stankovič, Milenko; Geršak, Borut

2012-01-01

We present a case of a 62-year old man with a left main stenosis, left coronary artery dominance, normal ejection fraction and no valvular pathology, and status post right carotid artery stenting, who was scheduled for elective coronary revascularization. We performed off-pump coronary revascularization, anastomosing the left internal thoracic artery to the left anterior descending artery, and three separate saphenous vein grafts to the intermediate artery and the first and second obtuse marginals, respectively. Proximally, the right internal thoracic artery was used as the inflow for all three venous grafts due to a heavily calcified ascending aorta. During the construction of the distal anastomoses to the obtuse marginals, the arterial pressure in the left radial artery suddenly dropped. The left hand was found to be pale and pulseless. A femoral artery catheter was placed for pressure monitoring and the anastomoses were completed as planned. Intraoperative transit-time graft flow measurement showed a reversed flow in the left internal thoracic artery. Postoperatively, angiography was performed showing a subtotal stenosis of the proximal left subclavian artery. The artery was dilated and stented. The postoperative course was uneventful and the patient was discharged on the 12th postoperative day. PMID:22767542

Bimanual proprioceptive performance differs for right- and left-handed individuals.

PubMed

Han, Jia; Waddington, Gordon; Adams, Roger; Anson, Judith

2013-05-10

It has been proposed that asymmetry between the upper limbs in the utilization of proprioceptive feedback arises from functional differences in the roles of the preferred and non-preferred hands during bimanual tasks. The present study investigated unimanual and bimanual proprioceptive performance in right- and left-handed young adults with an active finger pinch movement discrimination task. With visual information removed, participants were required to make absolute judgments about the extent of pinch movements made to physical stops, either by one hand, or by both hands concurrently, with the sequence of presented movement extents varied randomly. Discrimination accuracy scores were derived from participants' responses using non-parametric signal detection analysis. Consistent with previous findings, a non-dominant hand/hemisphere superiority effect was observed, where the non-dominant hands of right- and left-handed individuals performed overall significantly better than their dominant hands. For all participants, bimanual movement discrimination scores were significantly lower than scores obtained in the unimanual task. However, the magnitude of the performance reduction, from the unimanual to the bimanual task, was significantly greater for left-handed individuals. The effect whereby bimanual proprioception was disproportionately affected in left-handed individuals could be due to enhanced neural communication between hemispheres in left-handed individuals leading to less distinctive separation of information obtained from the two hands in the cerebral cortex. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.