Spatial enhancer clustering and regulation of enhancer-proximal genes by cohesin

PubMed Central

Ing-Simmons, Elizabeth; Seitan, Vlad C.; Faure, Andre J.; Flicek, Paul; Carroll, Thomas; Dekker, Job; Fisher, Amanda G.; Lenhard, Boris

2015-01-01

In addition to mediating sister chromatid cohesion during the cell cycle, the cohesin complex associates with CTCF and with active gene regulatory elements to form long-range interactions between its binding sites. Genome-wide chromosome conformation capture had shown that cohesin's main role in interphase genome organization is in mediating interactions within architectural chromosome compartments, rather than specifying compartments per se. However, it remains unclear how cohesin-mediated interactions contribute to the regulation of gene expression. We have found that the binding of CTCF and cohesin is highly enriched at enhancers and in particular at enhancer arrays or “super-enhancers” in mouse thymocytes. Using local and global chromosome conformation capture, we demonstrate that enhancer elements associate not just in linear sequence, but also in 3D, and that spatial enhancer clustering is facilitated by cohesin. The conditional deletion of cohesin from noncycling thymocytes preserved enhancer position, H3K27ac, H4K4me1, and enhancer transcription, but weakened interactions between enhancers. Interestingly, ∼50% of deregulated genes reside in the vicinity of enhancer elements, suggesting that cohesin regulates gene expression through spatial clustering of enhancer elements. We propose a model for cohesin-dependent gene regulation in which spatial clustering of enhancer elements acts as a unified mechanism for both enhancer-promoter “connections” and “insulation.” PMID:25677180

A new metasurface reflective structure for simultaneous enhancement of antenna bandwidth and gain

NASA Astrophysics Data System (ADS)

Ullah, M. Habib; Islam, M. T.

2014-08-01

A new bi-layered metasurface reflective structure (MRS) on a high-permittivity, low-loss, ceramic-filled, bio-plastic, sandwich-structured, dielectric substrate is proposed for the simultaneous enhancement of the bandwidth and gain of a dual band patch antenna. By incorporating the MRS with a 4 mm air gap between the MRS and the antenna, the bandwidth and gain of the dual band patch antenna are significantly enhanced. The reflection coefficient (S11 < -10 dB) bandwidth of the proposed MRS-loaded antenna increased by 240% (178%), and the average peak gain improved by 595% (128%) compared to the antenna alone in the lower (upper) band. Incremental improvements of the magnitude and directional patterns have been observed from the measured radiation patterns at the three resonant frequencies of 0.9 GHz, 3.7 GHz and 4.5 GHz. The effects of different configurations of the radiating patch and the ground plane on the reflection coefficient have been analyzed. In addition, the voltage standing wave ratio and input impedance have also been validated using a Smith chart.

Printed wide-slot antenna design with bandwidth and gain enhancement on low-cost substrate.

PubMed

Samsuzzaman, M; Islam, M T; Mandeep, J S; Misran, N

2014-01-01

This paper presents a printed wide-slot antenna design and prototyping on available low-cost polymer resin composite material fed by a microstrip line with a rotated square slot for bandwidth enhancement and defected ground structure for gain enhancement. An I-shaped microstrip line is used to excite the square slot. The rotated square slot is embedded in the middle of the ground plane, and its diagonal points are implanted in the middle of the strip line and ground plane. To increase the gain, four L-shaped slots are etched in the ground plane. The measured results show that the proposed structure retains a wide impedance bandwidth of 88.07%, which is 20% better than the reference antenna. The average gain is also increased, which is about 4.17 dBi with a stable radiation pattern in the entire operating band. Moreover, radiation efficiency, input impedance, current distribution, axial ratio, and parametric studies of S11 for different design parameters are also investigated using the finite element method-based simulation software HFSS.

Printed Wide-Slot Antenna Design with Bandwidth and Gain Enhancement on Low-Cost Substrate

PubMed Central

Samsuzzaman, M.; Islam, M. T.; Mandeep, J. S.; Misran, N.

2014-01-01

This paper presents a printed wide-slot antenna design and prototyping on available low-cost polymer resin composite material fed by a microstrip line with a rotated square slot for bandwidth enhancement and defected ground structure for gain enhancement. An I-shaped microstrip line is used to excite the square slot. The rotated square slot is embedded in the middle of the ground plane, and its diagonal points are implanted in the middle of the strip line and ground plane. To increase the gain, four L-shaped slots are etched in the ground plane. The measured results show that the proposed structure retains a wide impedance bandwidth of 88.07%, which is 20% better than the reference antenna. The average gain is also increased, which is about 4.17 dBi with a stable radiation pattern in the entire operating band. Moreover, radiation efficiency, input impedance, current distribution, axial ratio, and parametric studies of S11 for different design parameters are also investigated using the finite element method-based simulation software HFSS. PMID:24696661

Enhanced animal growth via ligand-regulated GHRH myogenic-injectable vectors

NASA Technical Reports Server (NTRS)

Draghia-Akli, Ruxandra; Malone, P. Brandon; Hill, Leigh Anne; Ellis, Kenneth M.; Schwartz, Robert J.; Nordstrom, Jeffrey L.

2002-01-01

Regulated animal growth occurred following a single electroporated injection of a mixture of two plasmids (10 microg of DNA), one expressing the GeneSwitch regulator protein, the other an inducible growth hormone releasing hormone (GHRH) gene, into the tibialis anterior muscles of adult SCID mice. Administration of the ligand mifepristone (MFP) up-regulated GHRH expression, as shown by elevations of IGF-I levels, and when MFP dosing was withdrawn, IGF-I returned to baseline levels. Five cycles of IGF-I induction were observed during a five-month period. Chronic MFP dosing for 25 days increased lean body mass, weight gain, and bone mineral density significantly compared with non-MFP treated controls. In summary, long-term drug-regulated GHRH expression was achieved following plasmid-based gene therapy, and chronic induction of GHRH expression in adult animals led to improvements in weight gain and body composition.

Enhanced animal growth via ligand-regulated GHRH myogenic-injectable vectors.

PubMed

Draghia-Akli, Ruxandra; Malone, P Brandon; Hill, Leigh Anne; Ellis, Kenneth M; Schwartz, Robert J; Nordstrom, Jeffrey L

2002-03-01

Regulated animal growth occurred following a single electroporated injection of a mixture of two plasmids (10 microg of DNA), one expressing the GeneSwitch regulator protein, the other an inducible growth hormone releasing hormone (GHRH) gene, into the tibialis anterior muscles of adult SCID mice. Administration of the ligand mifepristone (MFP) up-regulated GHRH expression, as shown by elevations of IGF-I levels, and when MFP dosing was withdrawn, IGF-I returned to baseline levels. Five cycles of IGF-I induction were observed during a five-month period. Chronic MFP dosing for 25 days increased lean body mass, weight gain, and bone mineral density significantly compared with non-MFP treated controls. In summary, long-term drug-regulated GHRH expression was achieved following plasmid-based gene therapy, and chronic induction of GHRH expression in adult animals led to improvements in weight gain and body composition.

Choosing to regulate: does choice enhance craving regulation?

PubMed Central

Mobasser, Arian; Zeithamova, Dagmar; Pfeifer, Jennifer H

2018-01-01

Abstract Goal-directed behavior and lifelong well-being often depend on the ability to control appetitive motivations, such as cravings. Cognitive reappraisal is an effective way to modulate emotional states, including cravings, but is often studied under explicit instruction to regulate. Despite the strong prediction from Self-Determination Theory that choice should enhance task engagement and regulation success, little is known empirically about whether and how regulation is different when participants choose (vs are told) to exert control. To investigate how choice affects neural activity and regulation success, participants reappraised their responses to images of personally-craved foods while undergoing functional neuroimaging. Participants were either instructed to view or reappraise (‘no-choice’) or chose freely to view or reappraise (‘yes-choice’). Choice increased activity in the frontoparietal control network. We expected this activity would be associated with increased task engagement, resulting in better regulation success. However, contrary to this prediction, choice slightly reduced regulation success. Follow-up multivariate functional neuroimaging analyses indicated that choice likely disrupted allocation of limited cognitive resources during reappraisal. While unexpected, these results highlight the importance of studying upstream processes such as regulation choice, as they may affect the ability to regulate cravings and other emotional states. PMID:29462475

Enhancing the Relationship Between Regulators and Their Profession.

PubMed

Austin, Zubin

2017-01-01

Regulators face unique pressures to balance competing priorities related to patient safety, public accountability, and practitioners' expectations. Historically, the collegial model of self-regulation has been used as a tool for risk management, to recognize the importance of profession- and context-specific judgment in complex, ambiguous clinical situations. Increasingly, as public accountability concerns have grown dominant within regulatory bodies, this collegial model has shifted toward a more antagonistic relationship between the regulators and the regulated. Wilkie and Tzountzouris (2017) highlight one profession's journey toward embedding professionalism within regulatory practices and policies through application of a right-touch regulatory philosophy. Given the complexity of regulatory work, this shift required significant strategic and deliberative thinking. The challenges of facilitating this sort of cultural shift in the role of a regulator are significant, but so too are the potential gains associated with a more engaged relationship between regulators and their practitioners.

Speech Enhancement, Gain, and Noise Spectrum Adaptation Using Approximate Bayesian Estimation

PubMed Central

Hao, Jiucang; Attias, Hagai; Nagarajan, Srikantan; Lee, Te-Won; Sejnowski, Terrence J.

2010-01-01

This paper presents a new approximate Bayesian estimator for enhancing a noisy speech signal. The speech model is assumed to be a Gaussian mixture model (GMM) in the log-spectral domain. This is in contrast to most current models in frequency domain. Exact signal estimation is a computationally intractable problem. We derive three approximations to enhance the efficiency of signal estimation. The Gaussian approximation transforms the log-spectral domain GMM into the frequency domain using minimal Kullback–Leiber (KL)-divergency criterion. The frequency domain Laplace method computes the maximum a posteriori (MAP) estimator for the spectral amplitude. Correspondingly, the log-spectral domain Laplace method computes the MAP estimator for the log-spectral amplitude. Further, the gain and noise spectrum adaptation are implemented using the expectation–maximization (EM) algorithm within the GMM under Gaussian approximation. The proposed algorithms are evaluated by applying them to enhance the speeches corrupted by the speech-shaped noise (SSN). The experimental results demonstrate that the proposed algorithms offer improved signal-to-noise ratio, lower word recognition error rate, and less spectral distortion. PMID:20428253

A numerical algorithm for optimal feedback gains in high dimensional linear quadratic regulator problems

NASA Technical Reports Server (NTRS)

Banks, H. T.; Ito, K.

1991-01-01

A hybrid method for computing the feedback gains in linear quadratic regulator problem is proposed. The method, which combines use of a Chandrasekhar type system with an iteration of the Newton-Kleinman form with variable acceleration parameter Smith schemes, is formulated to efficiently compute directly the feedback gains rather than solutions of an associated Riccati equation. The hybrid method is particularly appropriate when used with large dimensional systems such as those arising in approximating infinite-dimensional (distributed parameter) control systems (e.g., those governed by delay-differential and partial differential equations). Computational advantages of the proposed algorithm over the standard eigenvector (Potter, Laub-Schur) based techniques are discussed, and numerical evidence of the efficacy of these ideas is presented.

Low power analog front-end electronics in deep submicrometer CMOS technology based on gain enhancement techniques

NASA Astrophysics Data System (ADS)

Gómez-Galán, J. A.; Sánchez-Rodríguez, T.; Sánchez-Raya, M.; Martel, I.; López-Martín, A.; Carvajal, R. G.; Ramírez-Angulo, J.

2014-06-01

This paper evaluates the design of front-end electronics in modern technologies to be used in a new generation of heavy ion detectors—HYDE (FAIR, Germany)—proposing novel architectures to achieve high gain in a low voltage environment. As conventional topologies of operational amplifiers in modern CMOS processes show limitations in terms of gain, novel approaches must be raised. The work addresses the design using transistors with channel length of no more than double the feature size and a supply voltage as low as 1.2 V. A front-end system has been fabricated in a 90 nm process including gain boosting techniques based on regulated cascode circuits. The analog channel has been optimized to match a detector capacitance of 5 pF and exhibits a good performance in terms of gain, speed, linearity and power consumption.

Enhancement of short-pulse recombination-pumped gain by soft-x-ray photoionization of the ground state

NASA Astrophysics Data System (ADS)

Apruzese, J. P.; Umstadter, D.

1996-02-01

The gain achieved in lasing to the ground state following short-pulse field ionization by a pump laser is highly transient. It will usually persist for only tens of picoseconds because of the rapid filling and negligible emptying of the ground state. Employing a detailed atomic model of lasing in hydrogen, we show that the removal of ground-state population by an appropriate broadband ionizing radiation field can enhance and prolong the gain in such a laser.

Fast Ignition Thermonuclear Fusion: Enhancement of the Pellet Gain by the Colossal-Magnetic-Field Shells

NASA Astrophysics Data System (ADS)

Stefan, V. Alexander

2013-10-01

The fast ignition fusion pellet gain can be enhanced by a laser generated B-field shell. The B-field shell, (similar to Earth's B-field, but with the alternating B-poles), follows the pellet compression in a frozen-in B-field regime. A properly designed laser-pellet coupling can lead to the generation of a B-field shell, (up to 100 MG), which inhibits electron thermal transport and confines the alpha-particles. In principle, a pellet gain of few-100s can be achieved in this manner. Supported in part by Nikola Tesla Labs, Stefan University, 1010 Pearl, La Jolla, CA 92038-1007.

Gaining Regulator Acceptance of Natural Attenuation as a Remediation Tool

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

Hughes, M.B.

Monitored natural attenuation (MNA) makes use of biological degradation, chemical reactions with natural materials, and other processes to clean up contaminated soils and groundwater. In the past, the regulatory community has been slow to accept natural attenuation due to a misperception that natural attenuation is a ''do nothing'' approach. Recently however, regulators have been more open to considering MNA as part of an overall clean-up plan that includes active treatment technologies to remove or contain the source of contamination at a site. MNA is currently being implemented at the Savannah River Site for remediation of selected contaminants. The South Carolinamore » Department of Health and Environmental Control, who has regulatory authority over these actions, has accepted this process. Significant overall cost savings are forecast. Additionally, there will be less disruption to the ecosystem, compared with engineered technologies. This paper describes the monitored natural attenuation concept as well as the process of constructive engagement with the regulators to achieve acceptance. Application to DOE, DOD, and commercial sites, as well as acceptability to other regulatory bodies, will be discussed with an emphasis on strategies to prevent false starts in the negotiation process and inventing options that result in mutual gains for all parties.« less

93-133 GHz Band InP High-Electron-Mobility Transistor Amplifier with Gain-Enhanced Topology

NASA Astrophysics Data System (ADS)

Sato, Masaru; Shiba, Shoichi; Matsumura, Hiroshi; Takahashi, Tsuyoshi; Nakasha, Yasuhiro; Suzuki, Toshihide; Hara, Naoki

2013-04-01

In this study, we developed a new type of high-frequency amplifier topology using 75-nm-gate-length InP-based high-electron-mobility transistors (InP HEMTs). To enhance the gain for a wide frequency range, a common-source common-gate hybrid amplifier topology was proposed. A transformer-based balun placed at the input of the amplifier generates differential signals, which are fed to the gate and source terminals of the transistor. The amplified signal is outputted at the drain node. The simulation results show that the hybrid topology exhibits a higher gain from 90 to 140 GHz than that of the conventional common-source or common-gate amplifier. The two-stage amplifier fabricated using the topology exhibits a small signal gain of 12 dB and a 3-dB bandwidth of 40 GHz (93-133 GHz), which is the largest bandwidth and the second highest gain reported among those of published 120-GHz-band amplifiers. In addition, the measured noise figure was 5 dB from 90 to 100 GHz.

Transparency and Accountability: What if the Federal Gainful Employment-Debt Measures Regulations Applied to Law Schools?

ERIC Educational Resources Information Center

Mattox, Kari Ann

2013-01-01

The purpose of this analysis is to compare current guidelines of the American Bar Association (ABA) for law schools to those of the U.S. Department of Education's Gainful Employment-Debt Measures regulations in order to assess their transparency and accountability. This analysis is relevant in a time of increasing tuition costs and record…

Genome organization and long-range regulation of gene expression by enhancers

PubMed Central

Smallwood, Andrea; Ren, Bing

2014-01-01

It is now well accepted that cell-type specific gene regulation is under the purview of enhancers. Great strides have been made recently to characterize and identify enhancers both genetically and epigenetically for multiple cell types and species, but efforts have just begun to link enhancers to their target promoters. Mapping these interactions and understanding how the 3D landscape of the genome constrains such interactions is fundamental to our understanding of mammalian gene regulation. Here, we review recent progress in mapping long-range regulatory interactions in mammalian genomes, focusing on transcriptional enhancers and chromatin organization principles. PMID:23465541

Genome organization and long-range regulation of gene expression by enhancers.

PubMed

Smallwood, Andrea; Ren, Bing

2013-06-01

It is now well accepted that cell-type specific gene regulation is under the purview of enhancers. Great strides have been made recently to characterize and identify enhancers both genetically and epigenetically for multiple cell types and species, but efforts have just begun to link enhancers to their target promoters. Mapping these interactions and understanding how the 3D landscape of the genome constrains such interactions is fundamental to our understanding of mammalian gene regulation. Here, we review recent progress in mapping long-range regulatory interactions in mammalian genomes, focusing on transcriptional enhancers and chromatin organization principles. Copyright © 2013. Published by Elsevier Ltd.

Mapping of Human FOXP2 Enhancers Reveals Complex Regulation.

PubMed

Becker, Martin; Devanna, Paolo; Fisher, Simon E; Vernes, Sonja C

2018-01-01

Mutations of the FOXP2 gene cause a severe speech and language disorder, providing a molecular window into the neurobiology of language. Individuals with FOXP2 mutations have structural and functional alterations affecting brain circuits that overlap with sites of FOXP2 expression, including regions of the cortex, striatum, and cerebellum. FOXP2 displays complex patterns of expression in the brain, as well as in non-neuronal tissues, suggesting that sophisticated regulatory mechanisms control its spatio-temporal expression. However, to date, little is known about the regulation of FOXP2 or the genomic elements that control its expression. Using chromatin conformation capture (3C), we mapped the human FOXP2 locus to identify putative enhancer regions that engage in long-range interactions with the promoter of this gene. We demonstrate the ability of the identified enhancer regions to drive gene expression. We also show regulation of the FOXP2 promoter and enhancer regions by candidate regulators - FOXP family and TBR1 transcription factors. These data point to regulatory elements that may contribute to the temporal- or tissue-specific expression patterns of human FOXP2 . Understanding the upstream regulatory pathways controlling FOXP2 expression will bring new insight into the molecular networks contributing to human language and related disorders.

Mapping of Human FOXP2 Enhancers Reveals Complex Regulation

PubMed Central

Becker, Martin; Devanna, Paolo; Fisher, Simon E.; Vernes, Sonja C.

2018-01-01

Mutations of the FOXP2 gene cause a severe speech and language disorder, providing a molecular window into the neurobiology of language. Individuals with FOXP2 mutations have structural and functional alterations affecting brain circuits that overlap with sites of FOXP2 expression, including regions of the cortex, striatum, and cerebellum. FOXP2 displays complex patterns of expression in the brain, as well as in non-neuronal tissues, suggesting that sophisticated regulatory mechanisms control its spatio-temporal expression. However, to date, little is known about the regulation of FOXP2 or the genomic elements that control its expression. Using chromatin conformation capture (3C), we mapped the human FOXP2 locus to identify putative enhancer regions that engage in long-range interactions with the promoter of this gene. We demonstrate the ability of the identified enhancer regions to drive gene expression. We also show regulation of the FOXP2 promoter and enhancer regions by candidate regulators – FOXP family and TBR1 transcription factors. These data point to regulatory elements that may contribute to the temporal- or tissue-specific expression patterns of human FOXP2. Understanding the upstream regulatory pathways controlling FOXP2 expression will bring new insight into the molecular networks contributing to human language and related disorders. PMID:29515369

Enhancers and super-enhancers have an equivalent regulatory role in embryonic stem cells through regulation of single or multiple genes

PubMed Central

Moorthy, Sakthi D.; Davidson, Scott; Shchuka, Virlana M.; Singh, Gurdeep; Malek-Gilani, Nakisa; Langroudi, Lida; Martchenko, Alexandre; So, Vincent; Macpherson, Neil N.; Mitchell, Jennifer A.

2017-01-01

Transcriptional enhancers are critical for maintaining cell-type–specific gene expression and driving cell fate changes during development. Highly transcribed genes are often associated with a cluster of individual enhancers such as those found in locus control regions. Recently, these have been termed stretch enhancers or super-enhancers, which have been predicted to regulate critical cell identity genes. We employed a CRISPR/Cas9-mediated deletion approach to study the function of several enhancer clusters (ECs) and isolated enhancers in mouse embryonic stem (ES) cells. Our results reveal that the effect of deleting ECs, also classified as ES cell super-enhancers, is highly variable, resulting in target gene expression reductions ranging from 12% to as much as 92%. Partial deletions of these ECs which removed only one enhancer or a subcluster of enhancers revealed partially redundant control of the regulated gene by multiple enhancers within the larger cluster. Many highly transcribed genes in ES cells are not associated with a super-enhancer; furthermore, super-enhancer predictions ignore 81% of the potentially active regulatory elements predicted by cobinding of five or more pluripotency-associated transcription factors. Deletion of these additional enhancer regions revealed their robust regulatory role in gene transcription. In addition, select super-enhancers and enhancers were identified that regulated clusters of paralogous genes. We conclude that, whereas robust transcriptional output can be achieved by an isolated enhancer, clusters of enhancers acting on a common target gene act in a partially redundant manner to fine tune transcriptional output of their target genes. PMID:27895109

34 CFR 225.3 - What regulations apply to the Credit Enhancement for Charter School Facilities Program?

Code of Federal Regulations, 2013 CFR

2013-07-01

... Charter School Facilities Program? 225.3 Section 225.3 Education Regulations of the Offices of the... ENHANCEMENT FOR CHARTER SCHOOL FACILITIES PROGRAM General § 225.3 What regulations apply to the Credit Enhancement for Charter School Facilities Program? The following regulations apply to the Credit Enhancement...

34 CFR 225.3 - What regulations apply to the Credit Enhancement for Charter School Facilities Program?

Code of Federal Regulations, 2014 CFR

2014-07-01

... Charter School Facilities Program? 225.3 Section 225.3 Education Regulations of the Offices of the... ENHANCEMENT FOR CHARTER SCHOOL FACILITIES PROGRAM General § 225.3 What regulations apply to the Credit Enhancement for Charter School Facilities Program? The following regulations apply to the Credit Enhancement...

34 CFR 225.3 - What regulations apply to the Credit Enhancement for Charter School Facilities Program?

Code of Federal Regulations, 2012 CFR

2012-07-01

... Charter School Facilities Program? 225.3 Section 225.3 Education Regulations of the Offices of the... ENHANCEMENT FOR CHARTER SCHOOL FACILITIES PROGRAM General § 225.3 What regulations apply to the Credit Enhancement for Charter School Facilities Program? The following regulations apply to the Credit Enhancement...

34 CFR 225.3 - What regulations apply to the Credit Enhancement for Charter School Facilities Program?

Code of Federal Regulations, 2011 CFR

2011-07-01

... Charter School Facilities Program? 225.3 Section 225.3 Education Regulations of the Offices of the... ENHANCEMENT FOR CHARTER SCHOOL FACILITIES PROGRAM General § 225.3 What regulations apply to the Credit Enhancement for Charter School Facilities Program? The following regulations apply to the Credit Enhancement...

34 CFR 225.3 - What regulations apply to the Credit Enhancement for Charter School Facilities Program?

Code of Federal Regulations, 2010 CFR

2010-07-01

... Charter School Facilities Program? 225.3 Section 225.3 Education Regulations of the Offices of the... ENHANCEMENT FOR CHARTER SCHOOL FACILITIES PROGRAM General § 225.3 What regulations apply to the Credit Enhancement for Charter School Facilities Program? The following regulations apply to the Credit Enhancement...

MiR-155 Enhances Insulin Sensitivity by Coordinated Regulation of Multiple Genes in Mice

PubMed Central

Lin, Taoyan; Lin, Xia; Chen, Li; Zeng, Hui; Han, Yanjiang; Wu, Lihong; Huang, Shun; Wang, Meng; Huang, Shenhao; Xie, Raoying; Liang, Liqi; Liu, Yu; Liu, Ruiyu; Zhang, Tingting; Li, Jing; Wang, Shengchun; Sun, Penghui; Huang, Wenhua; Yao, Kaitai; Xu, Kang; Du, Tao; Xiao, Dong

2016-01-01

miR-155 plays critical roles in numerous physiological and pathological processes, however, its function in the regulation of blood glucose homeostasis and insulin sensitivity and underlying mechanisms remain unknown. Here, we reveal that miR-155 levels are downregulated in serum from type 2 diabetes (T2D) patients, suggesting that miR-155 might be involved in blood glucose control and diabetes. Gain-of-function and loss-of-function studies in mice demonstrate that miR-155 has no effects on the pancreatic β-cell proliferation and function. Global transgenic overexpression of miR-155 in mice leads to hypoglycaemia, improved glucose tolerance and insulin sensitivity. Conversely, miR-155 deficiency in mice causes hyperglycemia, impaired glucose tolerance and insulin resistance. In addition, consistent with a positive regulatory role of miR-155 in glucose metabolism, miR-155 positively modulates glucose uptake in all cell types examined, while mice overexpressing miR-155 transgene show enhanced glycolysis, and insulin-stimulated AKT and IRS-1 phosphorylation in liver, adipose tissue or skeletal muscle. Furthermore, we reveal these aforementioned phenomena occur, at least partially, through miR-155-mediated repression of important negative regulators (i.e. C/EBPβ, HDAC4 and SOCS1) of insulin signaling. Taken together, these findings demonstrate, for the first time, that miR-155 is a positive regulator of insulin sensitivity with potential applications for diabetes treatment. PMID:27711113

An enhanced velocity-based algorithm for safe implementations of gain-scheduled controllers

NASA Astrophysics Data System (ADS)

Lhachemi, H.; Saussié, D.; Zhu, G.

2017-09-01

This paper presents an enhanced velocity-based algorithm to implement gain-scheduled controllers for nonlinear and parameter-dependent systems. A new scheme including pre- and post-filtering is proposed with the assumption that the time-derivative of the controller inputs is not available for feedback control. It is shown that the proposed control structure can preserve the input-output properties of the linearised closed-loop system in the neighbourhood of each equilibrium point, avoiding the emergence of the so-called hidden coupling terms. Moreover, it is guaranteed that this implementation will not introduce unobservable or uncontrollable unstable modes, and hence the internal stability will not be affected. A case study dealing with the design of a pitch-axis missile autopilot is carried out and the numerical simulation results confirm the validity of the proposed approach.

The regulation of cognitive enhancement devices: extending the medical model

PubMed Central

Maslen, Hannah; Douglas, Thomas; Cohen Kadosh, Roi; Levy, Neil; Savulescu, Julian

2014-01-01

This article presents a model for regulating cognitive enhancement devices (CEDs). Recently, it has become very easy for individuals to purchase devices which directly modulate brain function. For example, transcranial direct current stimulators are increasingly being produced and marketed online as devices for cognitive enhancement. Despite posing risks in a similar way to medical devices, devices that do not make any therapeutic claims do not have to meet anything more than basic product safety standards. We present the case for extending existing medical device legislation to cover CEDs. Medical devices and CEDs operate by the same or similar mechanisms and pose the same or similar risks. This fact coupled with the arbitrariness of the line between treatment and enhancement count in favour of regulating these devices in the same way. In arguing for this regulatory model, the paper highlights potential challenges to its implementation, and suggests solutions. PMID:25243073

An Extended Normalization Model of Attention Accounts for Feature-Based Attentional Enhancement of Both Response and Coherence Gain

PubMed Central

Krishna, B. Suresh; Treue, Stefan

2016-01-01

Paying attention to a sensory feature improves its perception and impairs that of others. Recent work has shown that a Normalization Model of Attention (NMoA) can account for a wide range of physiological findings and the influence of different attentional manipulations on visual performance. A key prediction of the NMoA is that attention to a visual feature like an orientation or a motion direction will increase the response of neurons preferring the attended feature (response gain) rather than increase the sensory input strength of the attended stimulus (input gain). This effect of feature-based attention on neuronal responses should translate to similar patterns of improvement in behavioral performance, with psychometric functions showing response gain rather than input gain when attention is directed to the task-relevant feature. In contrast, we report here that when human subjects are cued to attend to one of two motion directions in a transparent motion display, attentional effects manifest as a combination of input and response gain. Further, the impact on input gain is greater when attention is directed towards a narrow range of motion directions than when it is directed towards a broad range. These results are captured by an extended NMoA, which either includes a stimulus-independent attentional contribution to normalization or utilizes direction-tuned normalization. The proposed extensions are consistent with the feature-similarity gain model of attention and the attentional modulation in extrastriate area MT, where neuronal responses are enhanced and suppressed by attention to preferred and non-preferred motion directions respectively. PMID:27977679

Should we use Commitment Contracts to Regulate Student use of Cognitive Enhancing Drugs?

PubMed

Danaher, John

2016-10-01

Are universities justified in trying to regulate student use of cognitive enhancing drugs? In this article I argue that they can be, but that the most appropriate kind of regulatory intervention is likely to be voluntary in nature. To be precise, I argue that universities could justifiably adopt a commitment contract system of regulation wherein students are encouraged to voluntarily commit to not using cognitive enhancing drugs (or to using them in a specific way). If they are found to breach that commitment, they should be penalized by, for example, forfeiting a number of marks on their assessments. To defend this model of regulation, I adopt a recently-proposed evaluative framework for determining the appropriateness of enhancement in specific domains of activity, and I focus on particular existing types of cognitive enhancement drugs, not hypothetical or potential forms. In this way, my argument is tailored to the specific features of university education, and common patterns of usage among students. It is not concerned with the general ethical propriety of using cognitive enhancing drugs. © 2016 John Wiley & Sons Ltd.

Does Documenting the Regulation Process on a Blog Enhance Pre-Service Teachers' Self- and Co-Regulation in a Collaborative Project?

ERIC Educational Resources Information Center

Cho, Moon-Heum; Lim, Seongmi; Lee, Kyeonghwa

2017-01-01

Students often complain about unsatisfactory experiences resulting from disproportionate contributions to collaborative projects. To improve the experience, we applied regulation theory to design a process to document regulation on a blog and examined whether such documentation enhanced students' self-regulation and co-regulation skills while…

Gain-of-Function Mutants of the Cytokinin Receptors AHK2 and AHK3 Regulate Plant Organ Size, Flowering Time and Plant Longevity1

PubMed Central

Bartrina, Isabel; Novák, Ondřej

2017-01-01

The phytohormone cytokinin is a regulator of numerous processes in plants. In Arabidopsis (Arabidopsis thaliana), the cytokinin signal is perceived by three membrane-located receptors named ARABIDOPSIS HISTIDINE KINASE2 (AHK2), AHK3, and AHK4/CRE1. How the signal is transmitted across the membrane is an entirely unknown process. The three receptors have been shown to operate mostly in a redundant fashion, and very few specific roles have been attributed to single receptors. Using a forward genetic approach, we isolated constitutively active gain-of-function variants of the AHK2 and AHK3 genes, named repressor of cytokinin deficiency2 (rock2) and rock3, respectively. It is hypothesized that the structural changes caused by these mutations in the sensory and adjacent transmembrane domains emulate the structural changes caused by cytokinin binding, resulting in domain motion propagating the signal across the membrane. Detailed analysis of lines carrying rock2 and rock3 alleles revealed how plants respond to locally enhanced cytokinin signaling. Early flowering time, a prolonged reproductive growth phase, and, thereby, increased seed yield suggest that cytokinin regulates various aspects of reproductive growth. In particular, it counteracts the global proliferative arrest, a correlative inhibition of maternal growth by seeds, an as yet unknown activity of the hormone. PMID:28096190

LRP8-Reelin-regulated Neuronal (LRN) Enhancer Signature Underlying Learning and Memory Formation

PubMed Central

Telese, Francesca; Ma, Qi; Perez, Patricia Montilla; Notani, Dimple; Oh, Soohwan; Li, Wenbo; Comoletti, Davide; Ohgi, Kenneth A.; Taylor, Havilah; Rosenfeld, Michael G.

2015-01-01

Summary One of the exceptional properties of the brain is its ability to acquire new knowledge through learning and to store that information through memory. The epigenetic mechanisms linking changes in neuronal transcriptional programs to behavioral plasticity remain largely unknown. Here, we identify the epigenetic signature of the neuronal enhancers required for transcriptional regulation of synaptic plasticity genes during memory formation, linking this to Reelin signaling. The binding of Reelin to its receptor, LRP8, triggers activation of this cohort of LRP8-Reelin-regulated-Neuronal (LRN) enhancers that serve as the ultimate convergence point of a novel synapse-to-nucleus pathway. Reelin simultaneously regulates NMDA-receptor transmission, which reciprocally permits the required, γ-secretase-dependent cleavage of LRP8, revealing an unprecedented role for its intracellular domain in the regulation of synaptically generated signals. These results uncover an in vivo enhancer code serving as a critical molecular component of cognition and relevant to psychiatric disorders linked to defects in Reelin signaling. PMID:25892301

Overexpression of Jazf1 reduces body weight gain and regulates lipid metabolism in high fat diet

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

Jang, Woo Young; Bae, Ki Beom; Kim, Sung Hyun

Highlights: • The expression of Jazf1 in the liver suppressed lipid accumulation. • Jazf1 significantly increases transcription of fatty acid synthase. • Jazf1 plays a critical role in the regulation of energy and lipid homeostasis. • Jazf1 associates the development of metabolic disorder. • Jazf1 may provide a new therapeutic target in the management of metabolic disorder. - Abstract: Jazf1 is a 27 kDa nuclear protein containing three putative zinc finger motifs that is associated with diabetes mellitus and prostate cancer; however, little is known about the role that this gene plays in regulation of metabolism. Recent evidence indicates thatmore » Jazf1 transcription factors bind to the nuclear orphan receptor TR4. This receptor regulates PEPCK, the key enzyme involved in gluconeogenesis. To elucidate Jazf1’s role in metabolism, we fed a 60% fat diet for up to 15 weeks. In Jazf1 overexpression mice, weight gain was found to be significantly decreased. The expression of Jazf1 in the liver also suppressed lipid accumulation and decreased droplet size. These results suggest that Jazf1 plays a critical role in the regulation of lipid homeostasis. Finally, Jazf1 may provide a new therapeutic target in the management of obesity and diabetes.« less

Cognitive emotion regulation enhances aversive prediction error activity while reducing emotional responses.

PubMed

Mulej Bratec, Satja; Xie, Xiyao; Schmid, Gabriele; Doll, Anselm; Schilbach, Leonhard; Zimmer, Claus; Wohlschläger, Afra; Riedl, Valentin; Sorg, Christian

2015-12-01

Cognitive emotion regulation is a powerful way of modulating emotional responses. However, despite the vital role of emotions in learning, it is unknown whether the effect of cognitive emotion regulation also extends to the modulation of learning. Computational models indicate prediction error activity, typically observed in the striatum and ventral tegmental area, as a critical neural mechanism involved in associative learning. We used model-based fMRI during aversive conditioning with and without cognitive emotion regulation to test the hypothesis that emotion regulation would affect prediction error-related neural activity in the striatum and ventral tegmental area, reflecting an emotion regulation-related modulation of learning. Our results show that cognitive emotion regulation reduced emotion-related brain activity, but increased prediction error-related activity in a network involving ventral tegmental area, hippocampus, insula and ventral striatum. While the reduction of response activity was related to behavioral measures of emotion regulation success, the enhancement of prediction error-related neural activity was related to learning performance. Furthermore, functional connectivity between the ventral tegmental area and ventrolateral prefrontal cortex, an area involved in regulation, was specifically increased during emotion regulation and likewise related to learning performance. Our data, therefore, provide first-time evidence that beyond reducing emotional responses, cognitive emotion regulation affects learning by enhancing prediction error-related activity, potentially via tegmental dopaminergic pathways. Copyright © 2015 Elsevier Inc. All rights reserved.

Do emotion regulation difficulties when upset influence the association between dietary restraint and weight gain among college students?

PubMed

Hunt, Tyler K; Forbush, Kelsie T; Hagan, Kelsey E; Chapa, Danielle A N

2017-07-01

Obesity is a significant public health concern that affects more than one-fifth of adolescents aged 12-19 in the United States. Theoretical models suggest that prolonged dietary restraint leads to binge-eating behaviors, which in turn increases individuals' risk for weight gain or obesity. Results from the literature indicate a potential role for negative urgency (the tendency to act rashly when distressed) as a mediating variable that explains the link between dietary restraint and binge-eating episodes. The current study tested short-term, prospective longitudinal associations among dietary restraint, binge eating, negative urgency, and weight gain among college students - a population at increased risk for the development of overweight and obesity. We hypothesized that dietary restraint and weight gain would be mediated by negative urgency and binge eating, but only among participants with overweight and obesity. College students (N = 227) completed the Eating Pathology Symptoms Inventory, UPPS-P Impulsivity Scale, and self-reported weight and height to calculate body mass index. Results showed that the association between dietary restraint and weight gain was mediated by negative urgency and binge eating, but only among participants with overweight and obesity. Our findings indicated that negative urgency might represent a mechanism that explains why dietary restraint leads to future binge-eating episodes and weight gain among college students with overweight and obesity. Results suggest that future treatment and prevention programs for overweight and obesity may benefit from incorporating strategies to improve emotion regulation as a way to reduce binge eating and to prevent additional weight gain among 'at-risk' populations. Copyright © 2017 Elsevier Ltd. All rights reserved.

Down-regulation of Transducin-Like Enhancer of Split protein 4 in hepatocellular carcinoma promotes cell proliferation and epithelial-Mesenchymal-Transition

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

Wu, Xiao-cai; Xiao, Cui-cui; Li, Hua

Background: Transducin-Like Enhancer of Split protein 4 (TLE4) has been reported to be involved in some subsets of acute myeloid leukemia and colorectal cancer. In the present study, we aimed to explore the role of TLE4 in tumorigenesis and cancer progression in hepatocellular carcinoma (HCC). Methods: The expression pattern of TLE4 in HCC was determined by Western-blot and qRT-PCR, gain-of-function and loss-of-function was used to explore the biological role of TLE4 in HCC cells. A xenograft model was established to confirm its effects on proliferation. Results: The protein expression levels of TLE4 were significantly down-regulated in HCC tissues compared tomore » matched adjacent normal liver tissues. In vitro, down-regulation of TLE4 in Huh7 or SMMC-7721 promoted cell proliferation and ectopical expression of TLE4 in Hep3B or Bel-7404 suppressed cell proliferation. In addition, the cell colony formation ability was enhanced after down-regulation of TLE4 expression in Huh-7 but suppressed after over-expression in Hep3B. Furthermore, down-regulation of TLE4 increased the cell invasion ability, as well as increased the expression level of Vimentin and decreased that of E-cadherin, indicating a phenotype of epithelial-mesenchymal transition (EMT) in HCC cells. On the contrary, ectopical expression of TLE4 in HCC cells decreased the cell invasion ability and inhibited EMT. In vivo, compared to control group, xenograft tumor volumes were significantly decreased in TLE4 overexpression group. Conclusions: These results demonstrated that TLE4 might play important regulatory roles in cellular proliferation and EMT process in HCC. - Highlights: • TLE4 is significantly down-regulated in HCC samples. • Down regulated of TLE4 in HCC cells promotes cell proliferation. • Down regulated of TLE4 in HCC cells promotes epithelial-to-mesenchymal transition.« less

Study of gain-coupled distributed feedback laser based on high order surface gain-coupled gratings

NASA Astrophysics Data System (ADS)

Gao, Feng; Qin, Li; Chen, Yongyi; Jia, Peng; Chen, Chao; Cheng, LiWen; Chen, Hong; Liang, Lei; Zeng, Yugang; Zhang, Xing; Wu, Hao; Ning, Yongqiang; Wang, Lijun

2018-03-01

Single-longitudinal-mode, gain-coupled distributed feedback (DFB) lasers based on high order surface gain-coupled gratings are achieved. Periodic surface metal p-contacts with insulated grooves realize gain-coupled mechanism. To enhance gain contrast in the quantum wells without the introduction of effective index-coupled effect, groove length and depth were well designed. Our devices provided a single longitudinal mode with the maximum CW output power up to 48.8 mW/facet at 971.31 nm at 250 mA without facet coating, 3dB linewidth (<3.2 pm) and SMSR (>39 dB). Optical bistable characteristic was observed with a threshold current difference. Experimentally, devices with different cavity lengths were contrasted on power-current and spectrum characteristics. Due to easy fabrication technique and stable performance, it provides a method of fabricating practical gain-coupled distributed feedback lasers for commercial applications.

SALICYLATE INCREASES THE GAIN OF THE CENTRAL AUDITORY SYSTEM

PubMed Central

Sun, W.; Lu, J.; Stolzberg, D.; Gray, L.; Deng, A.; Lobarinas, E.; Salvi, R. J.

2009-01-01

High doses of salicylate, the anti-inflammatory component of aspirin, induce transient tinnitus and hearing loss. Systemic injection of 250 mg/kg of salicylate, a dose that reliably induces tinnitus in rats, significantly reduced the sound evoked output of the rat cochlea. Paradoxically, salicylate significantly increased the amplitude of the sound-evoked field potential from the auditory cortex (AC) of conscious rats, but not the inferior colliculus (IC). When rats were anesthetized with isoflurane, which increases GABA-mediated inhibition, the salicylate-induced AC amplitude enhancement was abolished, whereas ketamine, which blocks N-methyl-d-aspartate receptors, further increased the salicylate-induced AC amplitude enhancement. Direct application of salicylate to the cochlea, however, reduced the response amplitude of the cochlea, IC and AC, suggesting the AC amplitude enhancement induced by systemic injection of salicylate does not originate from the cochlea. To identify a behavioral correlate of the salicylate-induced AC enhancement, the acoustic startle response was measured before and after salicylate treatment. Salicylate significantly increased the amplitude of the startle response. Collectively, these results suggest that high doses of salicylate increase the gain of the central auditory system, presumably by down-regulating GABA-mediated inhibition, leading to an exaggerated acoustic startle response. The enhanced startle response may be the behavioral correlate of hyperacusis that often accompanies tinnitus and hearing loss. Published by Elsevier Ltd on behalf of IBRO. PMID:19154777

Regulation of Urea Transporters by Tonicity-responsive Enhancer Binding Protein

PubMed Central

Kwon, H. Moo; Kim, Jim

2007-01-01

Urea accumulation in the renal inner medulla plays a key role in the maintenance of maximal urinary concentrating ability. Urea transport in the kidney is mediated by transporter proteins that include renal urea transporter (UT-A) and erythrocyte urea transporter (UT-B). UT-A1 and UT-A2 are produced from the same gene. There is an active tonicity-responsive enhancer (TonE) in the promoter of UT-A1, and the UT-A1 promoter is stimulated by hypertonicity via tonicity-responsive enhancer binding protein (TonEBP). The downregulation of UT-A2 raises the possibility that TonEBP also regulates its promoter. There is some evidence that TonEBP regulates expression of UT-A in vivo; (1) during the renal development of the urinary concentrating ability, expression of TonEBP precedes that of UT-A1; (2) in transgenic mice expressing a dominant negative form of TonEBP, expression of UT-A1 and UT-A2 is severely impaired; (3) in treatment with cyclosporine A, TonEBP was significantly downregulated after 28 days. This downregulation involves mRNA levels of UT-A2; (4) in hypokalemic animals, downregulation of TonEBP contributed to the down regulation of UT-A in the inner medulla. These data support that TonEBP directly contributes to the urinary concentration and renal urea recycling by the regulation of urea transporters. PMID:24459497

Medical regulation of cognitive enhancement devices: some concerns

PubMed Central

King, Mike; Gavaghan, Colin; McMillan, John

2014-01-01

The authors present a cogent and detailed case for altering the Medical Devices Directive to allow regulation of cognitive enhancement devices (CEDs). Protection against significant risk of harm, especially for the vulnerable, and promotion of benefit through informed use of CEDs are all good features of the proposal. However, the pre-market approval process has limitations, which we explore. We raise the possibility of ‘risk compensation’ in response to the introduction of safety measures, which could alter its effectiveness. The proposal alludes to use of ‘formally trained practitioners,’ which provide a further tier of regulation for CEDs within the proposal. We consider some positive and negative implications of this aspect of the proposal that might warrant further consideration. PMID:27774173

Federal regulation of vision enhancement devices for normal and abnormal vision

NASA Astrophysics Data System (ADS)

Drum, Bruce

2006-09-01

The Food and Drug Administration (FDA) evaluates the safety and effectiveness of medical devices and biological products as well as food and drugs. The FDA defines a device as a product that is intended, by physical means, to diagnose, treat, or prevent disease, or to affect the structure or function of the body. All vision enhancement devices fulfill this definition because they are intended to affect a function (vision) of the body. In practice, however, FDA historically has drawn a distinction between devices that are intended to enhance low vision as opposed to normal vision. Most low vision aids are therapeutic devices intended to compensate for visual impairment, and are actively regulated according to their level of risk to the patient. The risk level is usually low (e.g. Class I, exempt from 510(k) submission requirements for magnifiers that do not touch the eye), but can be as high as Class III (requiring a clinical trial and Premarket Approval (PMA) application) for certain implanted and prosthetic devices (e.g. intraocular telescopes and prosthetic retinal implants). In contrast, the FDA usually does not actively enforce its regulations for devices that are intended to enhance normal vision, are low risk, and do not have a medical intended use. However, if an implanted or prosthetic device were developed for enhancing normal vision, the FDA would likely decide to regulate it actively, because its intended use would entail a substantial medical risk to the user. Companies developing such devices should contact the FDA at an early stage to clarify their regulatory status.

Enhancer Sharing Promotes Neighborhoods of Transcriptional Regulation Across Eukaryotes

PubMed Central

Quintero-Cadena, Porfirio; Sternberg, Paul W.

2016-01-01

Enhancers physically interact with transcriptional promoters, looping over distances that can span multiple regulatory elements. Given that enhancer–promoter (EP) interactions generally occur via common protein complexes, it is unclear whether EP pairing is predominantly deterministic or proximity guided. Here, we present cross-organismic evidence suggesting that most EP pairs are compatible, largely determined by physical proximity rather than specific interactions. By reanalyzing transcriptome datasets, we find that the transcription of gene neighbors is correlated over distances that scale with genome size. We experimentally show that nonspecific EP interactions can explain such correlation, and that EP distance acts as a scaling factor for the transcriptional influence of an enhancer. We propose that enhancer sharing is commonplace among eukaryotes, and that EP distance is an important layer of information in gene regulation. PMID:27799341

77 FR 3121 - Program Integrity: Gainful Employment-Debt Measures; Correction

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-23

...On June 13, 2011, the Secretary of Education (Secretary) published a notice of final regulations in the Federal Register for Program Integrity: Gainful Employment--Debt Measures (Gainful Employment--Debt Measures) (76 FR 34386). In the preamble of the final regulations, we used the wrong data to calculate the percent of total variance in institutions' repayment rates that may be explained by race/ethnicity. Our intent was to use the data that included all minority students per institution. However, we mistakenly used the data for a subset of minority students per institution. We have now recalculated the total variance using the data that includes all minority students. Through this document, we correct, in the preamble of the Gainful Employment--Debt Measures final regulations, the errors resulting from this misapplication. We do not change the regression analysis model itself; we are using the same model with the appropriate data. Through this notice we also correct, in the preamble of the Gainful Employment--Debt Measures final regulations, our description of one component of the regression analysis. The preamble referred to use of an institutional variable measuring acceptance rates. This description was incorrect; in fact we used an institutional variable measuring retention rates. Correcting this language does not change the regression analysis model itself or the variance explained by the model. The text of the final regulations remains unchanged.

Enhanced gain and output power of a sealed-off rf-excited CO2 waveguide laser with gold-plated electrodes

NASA Astrophysics Data System (ADS)

Heeman-Ilieva, M. B.; Udalov, Yu. B.; Hoen, K.; Witteman, W. J.

1994-02-01

The small-signal gain and the laser output power have been measured in a cw sealed-off rf-excited CO2 waveguide laser for two different electrode materials, gold-plated copper and aluminum, at several excitation frequencies, gas pressures and mixture compositions. In the case of the gold-plated electrodes an enhancement of the gain up to a factor of 2 and the output power up to a factor of 1.4 with time at a frequency of 190 MHz and 60 Torr of 1:1:5+5% (CO2:N2:He+Xe) mixture is observed. This is believed to be the result of the gold catalytic activities which are favored by increased electrode temperatures and helium rich gas compositions.

Enhancer modularity and the evolution of new traits.

PubMed

Koshikawa, Shigeyuki

2015-01-01

Animals have modular cis-regulatory regions in their genomes, and expression of a single gene is often regulated by multiple enhancers residing in such a region. In the laboratory, and also in natural populations, loss of an enhancer can result in a loss of gene expression. Although only a few examples have been well characterized to date, some studies have suggested that an evolutionary gain of a new enhancer function can establish a new gene expression domain. Our recent study showed that Drosophila guttifera has more enhancers and additional expression domains of the wingless gene during the pupal stage, compared to D. melanogaster, and that these new features appear to have evolved in the ancestral lineage leading to D. guttifera. (1) Gain of a new expression domain of a developmental regulatory gene (toolkit gene), such as wingless, can cause co-option of the expression of its downstream genes to the new domain, resulting in duplication of a preexisting structure at this new body position. Recently, with the advancement of evo-devo studies, we have learned that the developmental regulatory systems are strikingly similar across various animal taxa, in spite of the great diversity of the animals' morphology. Even behind "new" traits, co-options of essential developmental genes from known systems are very common. We previously provided concrete evidence of gains of enhancer activities of a developmental regulatory gene underlying gains of new traits. (1) Broad occurrence of this scenario is testable and should be validated in the future.

Comparison of growth and metabolic regulation between wild, domesticated and transgenic salmonids.

USDA-ARS?s Scientific Manuscript database

To gain a better understanding of the aspects underlying normal and growth hormone enhanced growth in salmonids, quantitative expression analysis was performed for a number of genes related to muscle growth, metabolism, immunology and energy regulation. This analysis was performed in liver and musc...

A Systematic Survey and Characterization of Enhancers that Regulate Sox3 in Neuro-Sensory Development in Comparison with Sox2 Enhancers.

PubMed

Nishimura, Naoko; Kamimura, Yoshifumi; Ishida, Yoshiko; Takemoto, Tatsuya; Kondoh, Hisato; Uchikawa, Masanori

2012-11-22

Development of neural and sensory primordia at the early stages of embryogenesis depends on the activity of two B1 Sox transcription factors, Sox2 and Sox3. The embryonic expression patterns of the Sox2 and Sox3 genes are similar, yet they show gene-unique features. We screened for enhancers of the 231-kb genomic region encompassing Sox3 of chicken, and identified 13 new enhancers that showed activity in different domains of the neuro-sensory primordia. Combined with the three Sox3-proximal enhancers determined previously, at least 16 enhancers were involved in Sox3 regulation. Starting from the NP1 enhancer, more enhancers with different specificities are activated in sequence, resulting in complex overlapping patterns of enhancer activities. NP1 was activated in the caudal lateral epiblast adjacent to the posterior growing end of neural plate, and by the combined action of Wnt and Fgf signaling, similar to the Sox2 N1 enhancer involved in neural/mesodermal dichotomous cell lineage segregation. The Sox3 D5 enhancer and Sox2 N3 enhancer were also activated similarly in the diencephalon, optic vesicle and lens placode, suggesting analogies in their regulation. In general, however, the specificities of the enhancers were not identical between Sox3 and Sox2, including the cases of the NP1 and D5 enhancers.

Binocular combination of phase and contrast explained by a gain-control and gain-enhancement model

PubMed Central

Ding, Jian; Klein, Stanley A.; Levi, Dennis M.

2013-01-01

We investigated suprathreshold binocular combination, measuring both the perceived phase and perceived contrast of a cyclopean sine wave. We used a paradigm adapted from Ding and Sperling (2006, 2007) to measure the perceived phase by indicating the apparent location (phase) of the dark trough in the horizontal cyclopean sine wave relative to a black horizontal reference line, and we used the same stimuli to measure perceived contrast by matching the binocular combined contrast to a standard contrast presented to one eye. We found that under normal viewing conditions (high contrast and long stimulus duration), perceived contrast is constant, independent of the interocular contrast ratio and the interocular phase difference, while the perceived phase shifts smoothly from one eye to the other eye depending on the contrast ratios. However, at low contrasts and short stimulus durations, binocular combination is more linear and contrast summation is phase-dependent. To account for phase-dependent contrast summation, we incorporated a fusion remapping mechanism into our model, using disparity energy to shift the monocular phases towards the cyclopean phase in order to align the two eyes' images through motor/sensory fusion. The Ding-Sperling model with motor/sensory fusion mechanism gives a reasonable account of the phase dependence of binocular contrast combination and can account for either the perceived phase or the perceived contrast of a cyclopean sine wave separately; however it requires different model parameters for the two. However, when fit to both phase and contrast data simultaneously, the Ding-Sperling model fails. Incorporating interocular gain enhancement into the model results in a significant improvement in fitting both phase and contrast data simultaneously, successfully accounting for both linear summation at low contrast energy and strong nonlinearity at high contrast energy. PMID:23397038

Enhancing crop yield with the use of N-based fertilizers co-applied with plant hormones or growth regulators.

PubMed

Zaman, Mohammad; Kurepin, Leonid V; Catto, Warwick; Pharis, Richard P

2015-07-01

Crop yield, vegetative or reproductive, depends on access to an adequate supply of essential mineral nutrients. At the same time, a crop plant's growth and development, and thus yield, also depend on in situ production of plant hormones. Thus optimizing mineral nutrition and providing supplemental hormones are two mechanisms for gaining appreciable yield increases. Optimizing the mineral nutrient supply is a common and accepted agricultural practice, but the co-application of nitrogen-based fertilizers with plant hormones or plant growth regulators is relatively uncommon. Our review discusses possible uses of plant hormones (gibberellins, auxins, cytokinins, abscisic acid and ethylene) and specific growth regulators (glycine betaine and polyamines) to enhance and optimize crop yield when co-applied with nitrogen-based fertilizers. We conclude that use of growth-active gibberellins, together with a nitrogen-based fertilizer, can result in appreciable and significant additive increases in shoot dry biomass of crops, including forage crops growing under low-temperature conditions. There may also be a potential for use of an auxin or cytokinin, together with a nitrogen-based fertilizer, for obtaining additive increases in dry shoot biomass and/or reproductive yield. Further research, though, is needed to determine the potential of co-application of nitrogen-based fertilizers with abscisic acid, ethylene and other growth regulators. © 2014 Society of Chemical Industry.

78 FR 60169 - Federal Acquisition Regulation; Pilot Program for Enhancement of Contractor Employee...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-30

... 9000-AM56 Federal Acquisition Regulation; Pilot Program for Enhancement of Contractor Employee... program enhancing whistleblower protections for contractor employees. DATES: Effective: September 30, 2013... contractor employees at FAR subpart 3.9. The pilot program is mandated by section 828, entitled ``Pilot...

Efficiency enhancement of slow-wave electron-cyclotron maser by a second-order shaping of the magnetic field in the low-gain limit

NASA Astrophysics Data System (ADS)

Liu, Si-Jia; Zhang, Yu-Fei; Wang, Kang; Li, Yong-Ming; Jing, Jian

2017-03-01

Based on the anomalous Doppler effect, we put forward a proposal to enhance the conversion efficiency of the slow-wave electron cyclotron masers (ECM) under the resonance condition. Compared with previous studies, we add a second-order shaping term in the guild magnetic field. Theoretical analyses and numerical calculations show that it can enhance the conversion efficiency in the low-gain limit. The case of the initial velocity spread of electrons satisfying the Gaussian distribution is also analysed numerically.

Efficiency enhancement of slow-wave electron-cyclotron maser by a second-order shaping of the magnetic field in the low-gain limit

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

Liu, Si-Jia; Zhang, Yu-Fei; Wang, Kang

Based on the anomalous Doppler effect, we put forward a proposal to enhance the conversion efficiency of the slow-wave electron cyclotron masers (ECM) under the resonance condition. Compared with previous studies, we add a second-order shaping term in the guild magnetic field. Theoretical analyses and numerical calculations show that it can enhance the conversion efficiency in the low-gain limit. The case of the initial velocity spread of electrons satisfying the Gaussian distribution is also analysed numerically.

Regulation of Six1 expression by evolutionarily conserved enhancers in tetrapods.

PubMed

Sato, Shigeru; Ikeda, Keiko; Shioi, Go; Nakao, Kazuki; Yajima, Hiroshi; Kawakami, Kiyoshi

2012-08-01

The Six1 homeobox gene plays critical roles in vertebrate organogenesis. Mice deficient for Six1 show severe defects in organs such as skeletal muscle, kidney, thymus, sensory organs and ganglia derived from cranial placodes, and mutations in human SIX1 cause branchio-oto-renal syndrome, an autosomal dominant developmental disorder characterized by hearing loss and branchial defects. The present study was designed to identify enhancers responsible for the dynamic expression pattern of Six1 during mouse embryogenesis. The results showed distinct enhancer activities of seven conserved non-coding sequences (CNSs) retained in tetrapod Six1 loci. The activities were detected in all cranial placodes (excluding the lens placode), dorsal root ganglia, somites, nephrogenic cord, notochord and cranial mesoderm. The major Six1-expression domains during development were covered by the sum of activities of these enhancers, together with the previously identified enhancer for the pre-placodal region and foregut endoderm. Thus, the eight CNSs identified in a series of our study represent major evolutionarily conserved enhancers responsible for the expression of Six1 in tetrapods. The results also confirmed that chick electroporation is a robust means to decipher regulatory information stored in vertebrate genomes. Mutational analysis of the most conserved placode-specific enhancer, Six1-21, indicated that the enhancer integrates a variety of inputs from Sox, Pax, Fox, Six, Wnt/Lef1 and basic helix-loop-helix proteins. Positive autoregulation of Six1 is achieved through the regulation of Six protein-binding sites. The identified Six1 enhancers provide valuable tools to understand the mechanism of Six1 regulation and to manipulate gene expression in the developing embryo, particularly in the sensory organs. Copyright © 2012 Elsevier Inc. All rights reserved.

Memory Enhancement by Targeting Cdk5 Regulation of NR2B

PubMed Central

Plattner, Florian; Hernandéz, Adan; Kistler, Tara M.; Pozo, Karine; Zhong, Ping; Yuen, Eunice Y.; Tan, Chunfeng; Hawasli, Ammar H.; Cooke, Sam F.; Nishi, Akinori; Guo, Ailan; Wiederhold, Thorsten; Yan, Zhen; Bibb, James A.

2014-01-01

SUMMARY Many psychiatric and neurological disorders are characterized by learning and memory deficits, for which cognitive enhancement is considered a valid treatment strategy. The N-methyl-D-aspartate receptor (NMDAR) is a prime target for the development of cognitive enhancers due to its fundamental role in learning and memory. In particular, the NMDAR subunit NR2B improves synaptic plasticity and memory when over-expressed in neurons. However, NR2B regulation is not well understood and no therapies potentiating NMDAR function have been developed. Here, we show that serine 1116 of NR2B is phosphorylated by cyclin-dependent kinase 5 (Cdk5). Cdk5-dependent NR2B phosphorylation is regulated by neuronal activity and controls the receptor’s cell surface expression. Disrupting NR2B-Cdk5 interaction using a small interfering peptide (siP) increases NR2B surface levels, facilitates synaptic transmission, and improves memory formation in vivo. Our results reveal a novel regulatory mechanism critical to NR2B function that can be targeted for the development of cognitive enhancers. PMID:24607229

Regulation of hepatitis B virus ENI enhancer activity by hepatocyte-enriched transcription factor HNF3.

PubMed

Chen, M; Hieng, S; Qian, X; Costa, R; Ou, J H

1994-11-15

Hepatitis B virus (HBV) ENI enhancer can activate the expression of HBV and non-HBV genes in a liver-specific manner. By performing the electrophoretic mobility-shift assays, we demonstrated that the three related, liver-enriched, transcription factors, HNF3 alpha, HNF3 beta, and HNF3 gamma could all bind to the 2c site of HBV ENI enhancer. Mutations introduced in the 2c site to abolish the binding by HNF3 reduced the enhancer activity approximately 15-fold. Moreover, expression of HNF3 antisense sequences to suppress the expression of HNF3 in Huh-7 hepatoma cells led to reduction of the ENI enhancer activity. These results indicate that HNF3 positively regulates the ENI enhancer activity and this regulation is most likely mediated through the 2c site. The requirement of HNF3 for the ENI enhancer activity could explain the liver specificity of this enhancer element.

Approximate reversibility in the context of entropy gain, information gain, and complete positivity

NASA Astrophysics Data System (ADS)

Buscemi, Francesco; Das, Siddhartha; Wilde, Mark M.

2016-06-01

There are several inequalities in physics which limit how well we can process physical systems to achieve some intended goal, including the second law of thermodynamics, entropy bounds in quantum information theory, and the uncertainty principle of quantum mechanics. Recent results provide physically meaningful enhancements of these limiting statements, determining how well one can attempt to reverse an irreversible process. In this paper, we apply and extend these results to give strong enhancements to several entropy inequalities, having to do with entropy gain, information gain, entropic disturbance, and complete positivity of open quantum systems dynamics. Our first result is a remainder term for the entropy gain of a quantum channel. This result implies that a small increase in entropy under the action of a subunital channel is a witness to the fact that the channel's adjoint can be used as a recovery map to undo the action of the original channel. We apply this result to pure-loss, quantum-limited amplifier, and phase-insensitive quantum Gaussian channels, showing how a quantum-limited amplifier can serve as a recovery from a pure-loss channel and vice versa. Our second result regards the information gain of a quantum measurement, both without and with quantum side information. We find here that a small information gain implies that it is possible to undo the action of the original measurement if it is efficient. The result also has operational ramifications for the information-theoretic tasks known as measurement compression without and with quantum side information. Our third result shows that the loss of Holevo information caused by the action of a noisy channel on an input ensemble of quantum states is small if and only if the noise can be approximately corrected on average. We finally establish that the reduced dynamics of a system-environment interaction are approximately completely positive and trace preserving if and only if the data processing

A Technology-Enhanced Intervention for Self-Regulated Learning in Science

ERIC Educational Resources Information Center

Berglas-Shapiro, Tali; Eylon, Bat-Sheva; Scherz, Zahava

2017-01-01

This article describes the development of a technology-enhanced self-regulated learning (Te- SRL) environment designed to foster students' SRL of complex science topics. The environment consists of three components, one of which is a specially designed computerized system that offers students a choice between different types of scaffolding and…

A class of circadian long non-coding RNAs mark enhancers modulating long-range circadian gene regulation

PubMed Central

Fan, Zenghua; Zhao, Meng; Joshi, Parth D.; Li, Ping; Zhang, Yan; Guo, Weimin; Xu, Yichi; Wang, Haifang; Zhao, Zhihu

2017-01-01

Abstract Circadian rhythm exerts its influence on animal physiology and behavior by regulating gene expression at various levels. Here we systematically explored circadian long non-coding RNAs (lncRNAs) in mouse liver and examined their circadian regulation. We found that a significant proportion of circadian lncRNAs are expressed at enhancer regions, mostly bound by two key circadian transcription factors, BMAL1 and REV-ERBα. These circadian lncRNAs showed similar circadian phases with their nearby genes. The extent of their nuclear localization is higher than protein coding genes but less than enhancer RNAs. The association between enhancer and circadian lncRNAs is also observed in tissues other than liver. Comparative analysis between mouse and rat circadian liver transcriptomes showed that circadian transcription at lncRNA loci tends to be conserved despite of low sequence conservation of lncRNAs. One such circadian lncRNA termed lnc-Crot led us to identify a super-enhancer region interacting with a cluster of genes involved in circadian regulation of metabolism through long-range interactions. Further experiments showed that lnc-Crot locus has enhancer function independent of lnc-Crot's transcription. Our results suggest that the enhancer-associated circadian lncRNAs mark the genomic loci modulating long-range circadian gene regulation and shed new lights on the evolutionary origin of lncRNAs. PMID:28335007

Welfare Gains from Financial Liberalization

PubMed Central

Townsend, Robert M.; Ueda, Kenichi

2010-01-01

Financial liberalization has been a controversial issue, as empirical evidence for growth enhancing effects is mixed. Here, we find sizable welfare gains from liberalization (cost to repression), though the gain in economic growth is ambiguous. We take the view that financial liberalization is a government policy that alters the path of financial deepening, while financial deepening is endogenously chosen by agents given a policy and occurs in transition towards a distant steady state. This history-dependent view necessitates the use of simulation analysis based on a growth model. Our application is a specific episode: Thailand from 1976 to 1996. PMID:20806055

Gain and Bandwidth Enhancement of Ferrite-Loaded CBS Antenna Using Material Shaping and Positioning

NASA Astrophysics Data System (ADS)

Askarian Amiri, Mikal

Loading a cavity-backed slot (CBS) antenna with ferrite material and applying a biasing static magnetic field can be used to control its resonant frequency. Such a mechanism results in a frequency reconfigurable antenna. However, placing a lossy ferrite material inside the cavity can reduce the gain or negatively impact the impedance bandwidth. This thesis develops guidelines, based on a non-uniform applied magnetic field and non-uniform magnetic field internal to the ferrite specimen, for the design of ferrite-loaded CBS antennas which enhance their gain and tunable bandwidth by shaping the ferrite specimen and judiciously locating it within the cavity. To achieve these objectives, it is necessary to examine the influence of the shape and relative location of the ferrite material, and also the proximity of the ferrite specimen from the probe on the DC magnetic field and RF electric field distributions inside the cavity. The geometry of the probe and its impacts on figures-of-merit of the antenna is of interest as well. Two common cavity backed-slot antennas (rectangular and circular cross-section) were designed, and corresponding simulations and measurements were performed and compared. The cavities were mounted on 30 cm × 30 cm perfect electric conductor (PEC) ground planes and partially loaded with ferrite material. The ferrites were biased with an external magnetic field produced by either an electromagnet or permanent magnets. Simulations were performed using FEM-based commercial software, Ansys' Maxwell 3D and HFSS. Maxwell 3D is utilized to model the non-uniform DC applied magnetic field and non-uniform magnetic field internal to the ferrite specimen; HFSS however, is used to simulate and obtain the RF characteristics of the antenna. To validate the simulations they were compared with measurements performed in ASU's EM Anechoic Chamber. After many examinations using simulations and measurements, some optimal designs guidelines with respect to the gain

Excess noise in gain-guided amplifiers

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

Deutsch, I.H.; Garrison, J.C.; Wright, E.M.

1991-06-01

A second-quantized theory of the radiation field is used to study the origin of the excess noise observed in gain-guided amplifiers. We find that the reduction of the signal-to-noise ratio is a function of the length of the amplifier, and thus the enhancement of the noise is a propagation effect arising from longitudinally inhomogeneous gain of the noise rather than from an excess of local spontaneous emission. We confirm this conclusion by showing that the microscopic rate of spontaneous emission into a given non-power-orthogonal cavity mode is not enhanced by the Petermann factor. In addition, we illustrate the difficulties associatedmore » with photon statistics for this and other open systems by showing that no acceptable family of photon-number operators corresponds to a set of non-power-orthogonal cavity modes.« less

A transient-enhanced NMOS low dropout voltage regulator with parallel feedback compensation

NASA Astrophysics Data System (ADS)

Han, Wang; Lin, Tan

2016-02-01

This paper presents a transient-enhanced NMOS low-dropout regulator (LDO) for portable applications with parallel feedback compensation. The parallel feedback structure adds a dynamic zero to get an adequate phase margin with a load current variation from 0 to 1 A. A class-AB error amplifier and a fast charging/discharging unit are adopted to enhance the transient performance. The proposed LDO has been implemented in a 0.35 μm BCD process. From experimental results, the regulator can operate with a minimum dropout voltage of 150 mV at a maximum 1 A load and IQ of 165 μA. Under the full range load current step, the voltage undershoot and overshoot of the proposed LDO are reduced to 38 mV and 27 mV respectively.

CONDITIONS FOR CSR MICROBUNCHING GAIN SUPPRESSION

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

Tsai, Cheng Ying; Douglas, David R.; Li, Rui

The coherent synchrotron radiation (CSR) of a high brightness electron beam traversing a series of dipoles, such as transport arcs, may result in phase space degradation. On one hand, the CSR can perturb electron transverse motion in dispersive regions along the beamline, causing emittance growth. On the other hand, the CSR effect on the longitudinal beam dynamics could result in microbunching gain enhancement. For transport arcs, several schemes have been proposed* to suppress the CSR-induced emittance growth. Similarly, several scenarios have been introduced** to suppress CSR-induced microbunching gain, which however mostly aim for linac-based machines. In this paper we trymore » to provide sufficient conditions for suppression of CSR-induced microbunching gain along a transport arc, analogous to*. Several example lattices are presented, with the relevant microbunching analyses carried out by our semi-analytical Vlasov solver***. The simulation results show that lattices satisfying the proposed conditions indeed have microbunching gain suppressed. We expect this analysis can shed light on lattice design approach that could suppress the CSR-induced microbunching gain.« less

Hypothalamic ghrelin signalling mediates olanzapine-induced hyperphagia and weight gain in female rats.

PubMed

Zhang, Qingsheng; He, Meng; Deng, Chao; Wang, Hongqin; Lian, Jiamei; Huang, Xu-Feng

2014-05-01

Excessive weight gain is a major metabolic side effect of second-generation antipsychotics (SGAs) in the treatment of schizophrenia. Ghrelin is an orexigenic hormone secreted mainly from the stomach, which can induce weight gain and hyperphagia through regulating neuropeptides at the hypothalamus. Accumulating evidence implicates a relationship between ghrelin signalling and SGA-induced hyperphagia and weight gain. We report that olanzapine (a SGA with high weight gain liability) potently and time-dependently up-regulate ghrelin and ghrelin signalling, leading to hyperphagia and weight gain in female Sprague-Dawley rats, an action reversed by i.c.v. injection of a ghrelin receptor (GHS-R1a) antagonist. These findings indicate a crucial role of ghrelin signalling in hyperphagia induced by olanzapine, supporting the notion that GHS-R1a antagonist may be useful for pharmacological treatment of SGA-induced weight gain resulted from hyperphagia.

Comparing WTP values of different types of QALY gain elicited from the general public.

PubMed

Pennington, Mark; Baker, Rachel; Brouwer, Werner; Mason, Helen; Hansen, Dorte Gyrd; Robinson, Angela; Donaldson, Cam

2015-03-01

The appropriate thresholds for decisions on the cost-effectiveness of medical interventions remain controversial, especially in 'end-of-life' situations. Evidence of the values placed on different types of health gain by the general public is limited. Across nine European countries, 17,657 people were presented with different hypothetical health scenarios each involving a gain of one quality adjusted life year (QALY) and asked about their willingness to pay (WTP) for that gain. The questions included quality of life (QoL) enhancing and life extending health gains, and a scenario where respondents faced imminent, premature death. The mean WTP values for a one-QALY gain composed of QoL improvements were modest (PPP$11,000). When comparing QALY gains obtained in the near future, the valuation of life extension exceeded the valuation of QoL enhancing gains (mean WTP PPP$19,000 for a scenario in which a coma is avoided). The mean WTP values were higher still when respondents faced imminent, premature death (PPP$29,000). Evidence from the largest survey on the value of health gains by the general public indicated a higher value for life extending gains compared with QoL enhancing gains. A further modest premium may be indicated for life extension when facing imminent, premature death. Copyright © 2013 John Wiley & Sons, Ltd.

Depressive Symptoms Enhance Loss-Minimization, but Attenuate Gain-Maximization in History-Dependent Decision-Making

ERIC Educational Resources Information Center

Maddox, W. Todd; Gorlick, Marissa A.; Worthy, Darrell A.; Beevers, Christopher G.

2012-01-01

Individuals with depressive symptoms typically show deficits in decision-making. However, most work has emphasized decision-making under gain-maximization conditions. A gain-maximization framework may undermine decision-making when depressive symptoms are present because depressives are generally more sensitive to losses than gains. The present…

Measuring ability to enhance and suppress emotional expression: The Flexible Regulation of Emotional Expression (FREE) Scale.

PubMed

Burton, Charles L; Bonanno, George A

2016-08-01

Flexibility in self-regulatory behaviors has proved to be an important quality for adjusting to stressful life events and requires individuals to have a diverse repertoire of emotion regulation abilities. However, the most commonly used emotion regulation questionnaires assess frequency of behavior rather than ability, with little evidence linking these measures to observable capacity to enact a behavior. The aim of the current investigation was to develop and validate a Flexible Regulation of Emotional Expression (FREE) Scale that measures a person's ability to enhance and suppress displayed emotion across an array of hypothetical contexts. In Studies 1 and 2, a series of confirmatory factor analyses revealed that the FREE Scale consists of 4 first-order factors divided by regulation and emotional valence type that can contribute to 2 higher order factors: expressive enhancement ability and suppression ability. In Study 1, we also compared the FREE Scale to other commonly used emotion regulation measures, which revealed that suppression ability is conceptually distinct from suppression frequency. In Study 3, we compared the FREE Scale with a composite of traditional frequency-based indices of expressive regulation to predict performance in a previously validated emotional modulation paradigm. Participants' enhancement and suppression ability scores on the FREE Scale predicted their corresponding performance on the laboratory task, even when controlling for baseline expressiveness. These studies suggest that the FREE Scale is a valid and flexible measure of expressive regulation ability. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

78 FR 59851 - Defense Federal Acquisition Regulation Supplement: Enhancement of Contractor Employee...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-30

...-AH97 Defense Federal Acquisition Regulation Supplement: Enhancement of Contractor Employee... contractor and subcontractor employees. DATES: Effective date: September 30, 2013. In accordance with FAR 1... Whistleblower Protections for Contractor Employees) made extensive changes to 10 U.S.C. 2409, entitled...

Gain-of-function mutation in FGFR3 in mice leads to decreased bone mass by affecting both osteoblastogenesis and osteoclastogenesis

PubMed Central

Su, Nan; Sun, Qidi; Li, Can; Lu, Xiumin; Qi, Huabing; Chen, Siyu; Yang, Jing; Du, Xiaolan; Zhao, Ling; He, Qifen; Jin, Min; Shen, Yue; Chen, Di; Chen, Lin

2010-01-01

Achondroplasia (ACH) is a short-limbed dwarfism resulting from gain-of-function mutations in fibroblast growth factor receptor 3 (FGFR3). Previous studies have shown that ACH patients have impaired chondrogenesis, but the effects of FGFR3 on bone formation and bone remodeling at adult stages of ACH have not been fully investigated. Using micro-computed tomography and histomorphometric analyses, we found that 2-month-old Fgfr3G369C/+ mice (mouse model mimicking human ACH) showed decreased bone mass due to reduced trabecular bone volume and bone mineral density, defect in bone mineralization and increased osteoclast numbers and activity. Compared with primary cultures of bone marrow stromal cells (BMSCs) from wild-type mice, Fgfr3G369C/+ cultures showed decreased cell proliferation, increased osteogenic differentiation including up-regulation of alkaline phosphatase activity and expressions of osteoblast marker genes, and reduced bone matrix mineralization. Furthermore, our studies also suggest that decreased cell proliferation and enhanced osteogenic differentiation observed in Fgfr3G369C/+ BMSCs are caused by up-regulation of p38 phosphorylation and that enhanced Erk1/2 activity is responsible for the impaired bone matrix mineralization. In addition, in vitro osteoclast formation and bone resorption assays demonstrated that osteoclast numbers and bone resorption area were increased in cultured bone marrow cells derived from Fgfr3G369C/+ mice. These findings demonstrate that gain-of-function mutation in FGFR3 leads to decreased bone mass by regulating both osteoblast and osteoclast activities. Our studies provide new insight into the mechanism underlying the development of ACH. PMID:20053668

20 CFR 220.29 - Work that is considered substantial gainful activity.

Code of Federal Regulations, 2011 CFR

2011-04-01

... Employment § 220.29 Work that is considered substantial gainful activity. Work is considered to be substantial gainful activity if it— (a) Involves doing significant and productive physical or mental duties... activity. 220.29 Section 220.29 Employees' Benefits RAILROAD RETIREMENT BOARD REGULATIONS UNDER THE...

20 CFR 220.29 - Work that is considered substantial gainful activity.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Employment § 220.29 Work that is considered substantial gainful activity. Work is considered to be substantial gainful activity if it— (a) Involves doing significant and productive physical or mental duties... activity. 220.29 Section 220.29 Employees' Benefits RAILROAD RETIREMENT BOARD REGULATIONS UNDER THE...

Effect of body weight gain on insulin sensitivity after retirement from exercise training

NASA Technical Reports Server (NTRS)

Dolkas, Constantine B.; Rodnick, Kenneth J.; Mondon, Carl E.

1990-01-01

The effect of the body-weight gain after retirement from an exercise-training program on the retained increase in insulin sensitivity elicited by the training was investigated in exercise-trained (ET) rats. Insulin sensitivity was assessed by oral glucose tolerance and insulin suppression tests immediately after training and during retirement. Results show that, compared with sedentary controls, exercise training enhanced insulin-induced glucose uptake, but the enhanced sensitivity was gradually lost with the end of running activity until after seven days of retirement, when it became equal to that of controls. This loss of enhanced sensitivity to insulin was associated with an accelerated gain in body weight beginning one day after the start of retirement. However, those animals that gained weight only at rates similar to those of control rats, retained their enhanced sensitivity to insulin.

MED12 Regulates HSC-Specific Enhancers Independently of Mediator Kinase Activity to Control Hematopoiesis.

PubMed

Aranda-Orgilles, Beatriz; Saldaña-Meyer, Ricardo; Wang, Eric; Trompouki, Eirini; Fassl, Anne; Lau, Stephanie; Mullenders, Jasper; Rocha, Pedro P; Raviram, Ramya; Guillamot, María; Sánchez-Díaz, María; Wang, Kun; Kayembe, Clarisse; Zhang, Nan; Amoasii, Leonela; Choudhuri, Avik; Skok, Jane A; Schober, Markus; Reinberg, Danny; Sicinski, Piotr; Schrewe, Heinrich; Tsirigos, Aristotelis; Zon, Leonard I; Aifantis, Iannis

2016-12-01

Hematopoietic-specific transcription factors require coactivators to communicate with the general transcription machinery and establish transcriptional programs that maintain hematopoietic stem cell (HSC) self-renewal, promote differentiation, and prevent malignant transformation. Mediator is a large coactivator complex that bridges enhancer-localized transcription factors with promoters, but little is known about Mediator function in adult stem cell self-renewal and differentiation. We show that MED12, a member of the Mediator kinase module, is an essential regulator of HSC homeostasis, as in vivo deletion of Med12 causes rapid bone marrow aplasia leading to acute lethality. Deleting other members of the Mediator kinase module does not affect HSC function, suggesting kinase-independent roles of MED12. MED12 deletion destabilizes P300 binding at lineage-specific enhancers, resulting in H3K27Ac depletion, enhancer de-activation, and consequent loss of HSC stemness signatures. As MED12 mutations have been described recently in blood malignancies, alterations in MED12-dependent enhancer regulation may control both physiological and malignant hematopoiesis. Copyright © 2016 Elsevier Inc. All rights reserved.

Enhancing well-being at work: The role of emotion regulation skills as personal resources.

PubMed

Buruck, Gabriele; Dörfel, Denise; Kugler, Joachim; Brom, Sarah Susanne

2016-10-01

Dealing with negative emotions is a crucial work demand, particularly for employees in health care. Job resources (e.g., autonomy, social support, or reward) but also personal resources (such as emotion regulation strategies) might reduce job stress and support well-being. Following this, the present study focused on strengthening emotion regulation as 1 way of dealing with high job demands. The aim of this study was to evaluate the impact of a standardized emotion regulation training (Affect Regulation Training [ART]; Berking, 2010) to improve emotion regulation skills and well-being of employees in elderly health care. Therefore, 96 elderly care workers filled out an established questionnaire of emotion regulation skills as well as a measure of well-being at pretreatment, posttreatment and at 6-month follow-up. The findings show that the ART fosters emotion regulation skills. In particularly, acceptance, tolerance, and modification of negative emotions was enhanced in the training groups in comparison to a control-group. Modification, meaning the ability to actively change emotions, improved even more over the follow-up-period. Simultaneously, well-being of participants increased over all measurement time points in the ART-group compared with the control-group. Additionally, the improvement in emotion regulation skills from pre to posttreatment was related to well-being at follow-up. In summary, our results support the ART as an effective intervention for dealing with negative emotions and to enhance well-being among employees in elderly care. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

TEAD and YAP regulate the enhancer network of human embryonic pancreatic progenitors.

PubMed

Cebola, Inês; Rodríguez-Seguí, Santiago A; Cho, Candy H-H; Bessa, José; Rovira, Meritxell; Luengo, Mario; Chhatriwala, Mariya; Berry, Andrew; Ponsa-Cobas, Joan; Maestro, Miguel Angel; Jennings, Rachel E; Pasquali, Lorenzo; Morán, Ignasi; Castro, Natalia; Hanley, Neil A; Gomez-Skarmeta, Jose Luis; Vallier, Ludovic; Ferrer, Jorge

2015-05-01

The genomic regulatory programmes that underlie human organogenesis are poorly understood. Pancreas development, in particular, has pivotal implications for pancreatic regeneration, cancer and diabetes. We have now characterized the regulatory landscape of embryonic multipotent progenitor cells that give rise to all pancreatic epithelial lineages. Using human embryonic pancreas and embryonic-stem-cell-derived progenitors we identify stage-specific transcripts and associated enhancers, many of which are co-occupied by transcription factors that are essential for pancreas development. We further show that TEAD1, a Hippo signalling effector, is an integral component of the transcription factor combinatorial code of pancreatic progenitor enhancers. TEAD and its coactivator YAP activate key pancreatic signalling mediators and transcription factors, and regulate the expansion of pancreatic progenitors. This work therefore uncovers a central role for TEAD and YAP as signal-responsive regulators of multipotent pancreatic progenitors, and provides a resource for the study of embryonic development of the human pancreas.

24 CFR 3280.507 - Comfort heat gain.

Code of Federal Regulations, 2010 CFR

2010-04-01

... DEVELOPMENT MANUFACTURED HOME CONSTRUCTION AND SAFETY STANDARDS Thermal Protection § 3280.507 Comfort heat... 24 Housing and Urban Development 5 2010-04-01 2010-04-01 false Comfort heat gain. 3280.507 Section 3280.507 Housing and Urban Development Regulations Relating to Housing and Urban Development (Continued...

26 CFR 1.58-8 - Capital gains and stock options.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 26 Internal Revenue 1 2010-04-01 2010-04-01 true Capital gains and stock options. 1.58-8 Section 1... Tax Preference Regulations § 1.58-8 Capital gains and stock options. (a) In general. Section 58(g)(2) provides that the items of tax preference specified in section 57(a)(6), and § 1.57-1(b) (stock options...

18 CFR 11.13 - Energy gains calculations.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Energy gains calculations. 11.13 Section 11.13 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY REGULATIONS UNDER THE FEDERAL POWER ACT ANNUAL CHARGES UNDER PART I OF THE...

18 CFR 11.13 - Energy gains calculations.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 18 Conservation of Power and Water Resources 1 2012-04-01 2012-04-01 false Energy gains calculations. 11.13 Section 11.13 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY REGULATIONS UNDER THE FEDERAL POWER ACT ANNUAL CHARGES UNDER PART I OF THE...

18 CFR 11.13 - Energy gains calculations.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 18 Conservation of Power and Water Resources 1 2011-04-01 2011-04-01 false Energy gains calculations. 11.13 Section 11.13 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY REGULATIONS UNDER THE FEDERAL POWER ACT ANNUAL CHARGES UNDER PART I OF THE...

18 CFR 11.13 - Energy gains calculations.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 18 Conservation of Power and Water Resources 1 2014-04-01 2014-04-01 false Energy gains calculations. 11.13 Section 11.13 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY REGULATIONS UNDER THE FEDERAL POWER ACT ANNUAL CHARGES UNDER PART I OF THE...

18 CFR 11.13 - Energy gains calculations.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 18 Conservation of Power and Water Resources 1 2013-04-01 2013-04-01 false Energy gains calculations. 11.13 Section 11.13 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY REGULATIONS UNDER THE FEDERAL POWER ACT ANNUAL CHARGES UNDER PART I OF THE...

Arabidopsis thaliana G2-LIKE FLAVONOID REGULATOR and BRASSINOSTEROID ENHANCED EXPRESSION1 are low-temperature regulators of flavonoid accumulation.

PubMed

Petridis, Antonios; Döll, Stefanie; Nichelmann, Lars; Bilger, Wolfgang; Mock, Hans-Peter

2016-08-01

Flavonoid synthesis is predominantly regulated at the transcriptional level through the MYB-basic helix-loop-helix (bHLH)-WD40 (MBW) (MYB: transcription factor of the myeloblastosis protein family, WD40: tanscription factor with a short structural motif of 40 amino acids which terminates in an aspartic acid-tryptophan dipeptide) complex, and responds to both environmental and developmental stimuli. Although the developmental regulation of flavonoid accumulation in Arabidopsis thaliana has been examined in great detail, the response of the flavonoid synthesis pathway to abiotic stress (particularly low temperature) remains unclear. A screen of a Dissociation element (Ds) transposon-induced mutation collection identified two lines which exhibited an altered profile of phenylpropanoid accumulation following exposure to low-temperature stress. One of the mutated genes (BRASSINOSTEROID ENHANCED EXPRESSION1 (BEE1)) encoded a brassinosteroid enhanced expression transcription factor, while the other (G2-LIKE FLAVONOID REGULATOR (GFR)) encoded a G2-like flavonoid regulator. Phenylpropanoid-targeted analysis was performed using high-performance LC-MS, and gene expression analysis using quantitative reverse transcription-PCR. In both mutants, the accumulation of quercetins and scopolin was reduced under low-temperature growing conditions, whereas that of anthocyanin was increased. BEE1 and GFR were both shown to negatively regulate anthocyanin accumulation by inhibiting anthocyanin synthesis genes via the suppression of the bHLH (TRANSPARENT TESTA8 (TT8) and GLABROUS3 (GL3)) and/or the MYB (PRODUCTION OF ANTHOCYANIN PIGMENTS2 (PAP2)) components of the MBW complex. Our results provide new insight into the regulatory control of phenylpropanoid metabolism at low temperatures, and reveal that BEE1 and GFR act as important components of the signal transduction chain. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.

Dialogue and Structure: Enabling Learner Self-Regulation in Technology-Enhanced Learning Environments

ERIC Educational Resources Information Center

Andrade, Maureen Snow

2014-01-01

Distance learning that incorporates technology-enhanced learning environments provides a solution to the ever-increasing global demand for higher education. To be successful in these contexts, learners must be self-regulated, or have the ability to control the factors affecting their learning. Based on the theories of transactional distance,…

75 FR 26916 - Federal Acquisition Regulation: FAR Case 2009-004, Enhancing Contract Transparency

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-13

... Regulation: FAR Case 2009-004, Enhancing Contract Transparency AGENCY: Department of Defense (DoD), General... commercial or financial information. This transparency effort is intended to promote efficiency in Government... the Administration's memorandum entitled Transparency and Open Government (January 21, 2009...

Addiction-Related Gene Regulation: Risks of Exposure to Cognitive Enhancers vs. Other Psychostimulants

PubMed Central

Steiner, Heinz; Van Waes, Vincent

2012-01-01

The psychostimulants methylphenidate (Ritalin, Concerta), amphetamine (Adderall), and modafinil (Provigil) are widely used in the treatment of medical conditions such as attention-deficit hyperactivity disorder and narcolepsy and, increasingly, as “cognitive enhancers” by healthy people. The long-term neuronal effects of these drugs, however, are poorly understood. A substantial amount of research over the past 2 decades has investigated the effects of psychostimulants such as cocaine and amphetamines on gene regulation in the brain because these molecular changes are considered critical for psychostimulant addiction. This work has determined in some detail the neurochemical and cellular mechanisms that mediate psychostimulant-induced gene regulation and has also identified the neuronal systems altered by these drugs. Among the most affected brain systems are corticostriatal circuits, which are part of cortico-basal ganglia-cortical loops that mediate motivated behavior. The neurotransmitters critical for such gene regulation are dopamine in interaction with glutamate, while other neurotransmitters (e.g., serotonin) play modulatory roles. This review presents (1) an overview of the main findings on cocaine- and amphetamine-induced gene regulation in corticostriatal circuits in an effort to provide a cellular framework for (2) an assessment of the molecular changes produced by methylphenidate, medical amphetamine (Adderall), and modafinil. The findings lead to the conclusion that protracted exposure to these cognitive enhancers can induce gene regulation effects in corticostriatal circuits that are qualitatively similar to those of cocaine and other amphetamines. These neuronal changes may contribute to the addiction liability of the psychostimulant cognitive enhancers. PMID:23085425

Gain in three-dimensional metamaterials utilizing semiconductor quantum structures

NASA Astrophysics Data System (ADS)

Schwaiger, Stephan; Klingbeil, Matthias; Kerbst, Jochen; Rottler, Andreas; Costa, Ricardo; Koitmäe, Aune; Bröll, Markus; Heyn, Christian; Stark, Yuliya; Heitmann, Detlef; Mendach, Stefan

2011-10-01

We demonstrate gain in a three-dimensional metal/semiconductor metamaterial by the integration of optically active semiconductor quantum structures. The rolling-up of a metallic structure on top of strained semiconductor layers containing a quantum well allows us to achieve a tightly bent superlattice consisting of alternating layers of lossy metallic and amplifying gain material. We show that the transmission through the superlattice can be enhanced by exciting the quantum well optically under both pulsed or continuous wave excitation. This points out that our structures can be used as a starting point for arbitrary three-dimensional metamaterials including gain.

75 FR 33990 - Built-in Gains and Losses Under Section 382(h)

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-16

... Gains and Losses Under Section 382(h) AGENCY: Internal Revenue Service (IRS), Treasury. ACTION: Final... section 382(h). DATES: Effective Date: These regulations are effective on June 11, 2010. Applicability...) regarding the treatment of prepaid income under the built-in gain provisions of section 382(h) were...

Regulation of Blood Glucose Concentration in Type 1 Diabetics Using Single Order Sliding Mode Control Combined with Fuzzy On-line Tunable Gain, a Simulation Study

PubMed Central

Dinani, Soudabeh Taghian; Zekri, Maryam; Kamali, Marzieh

2015-01-01

Diabetes is considered as a global affecting disease with an increasing contribution to both mortality rate and cost damage in the society. Therefore, tight control of blood glucose levels has gained significant attention over the decades. This paper proposes a method for blood glucose level regulation in type 1 diabetics. The control strategy is based on combining the fuzzy logic theory and single order sliding mode control (SOSMC) to improve the properties of sliding mode control method and to alleviate its drawbacks. The aim of the proposed controller that is called SOSMC combined with fuzzy on-line tunable gain is to tune the gain of the controller adaptively. This merit causes a less amount of control effort, which is the rate of insulin delivered to the patient body. As a result, this method can decline the risk of hypoglycemia, a lethal phenomenon in regulating blood glucose level in diabetics caused by a low blood glucose level. Moreover, it attenuates the chattering observed in SOSMC significantly. It is worth noting that in this approach, a mathematical model called minimal model is applied instead of the intravenously infused insulin–blood glucose dynamics. The simulation results demonstrate a good performance of the proposed controller in meal disturbance rejection and robustness against parameter changes. In addition, this method is compared to fuzzy high-order sliding mode control (FHOSMC) and the superiority of the new method compared to FHOSMC is shown in the results. PMID:26284169

Regulation of Blood Glucose Concentration in Type 1 Diabetics Using Single Order Sliding Mode Control Combined with Fuzzy On-line Tunable Gain, a Simulation Study.

PubMed

Dinani, Soudabeh Taghian; Zekri, Maryam; Kamali, Marzieh

2015-01-01

Diabetes is considered as a global affecting disease with an increasing contribution to both mortality rate and cost damage in the society. Therefore, tight control of blood glucose levels has gained significant attention over the decades. This paper proposes a method for blood glucose level regulation in type 1 diabetics. The control strategy is based on combining the fuzzy logic theory and single order sliding mode control (SOSMC) to improve the properties of sliding mode control method and to alleviate its drawbacks. The aim of the proposed controller that is called SOSMC combined with fuzzy on-line tunable gain is to tune the gain of the controller adaptively. This merit causes a less amount of control effort, which is the rate of insulin delivered to the patient body. As a result, this method can decline the risk of hypoglycemia, a lethal phenomenon in regulating blood glucose level in diabetics caused by a low blood glucose level. Moreover, it attenuates the chattering observed in SOSMC significantly. It is worth noting that in this approach, a mathematical model called minimal model is applied instead of the intravenously infused insulin-blood glucose dynamics. The simulation results demonstrate a good performance of the proposed controller in meal disturbance rejection and robustness against parameter changes. In addition, this method is compared to fuzzy high-order sliding mode control (FHOSMC) and the superiority of the new method compared to FHOSMC is shown in the results.

Networking Senescence-Regulating Pathways by Using Arabidopsis Enhancer Trap Lines1

PubMed Central

He, Yuehui; Tang, Weining; Swain, Johnnie D.; Green, Anthony L.; Jack, Thomas P.; Gan, Susheng

2001-01-01

The last phase of leaf development, generally referred to as leaf senescence, is an integral part of plant development that involves massive programmed cell death. Due to a sharp decline of photosynthetic capacity in a leaf, senescence limits crop yield and forest plant biomass production. However, the biochemical components and regulatory mechanisms underlying leaf senescence are poorly characterized. Although several approaches such as differential cDNA screening, differential display, and cDNA subtraction have been employed to isolate senescence-associated genes (SAGs), only a limited number of SAGs have been identified, and information regarding the regulation of these genes is fragmentary. Here we report on the utilization of enhancer trap approach toward the identification and analysis of SAGs. We have developed a sensitive large-scale screening method and have screened 1,300 Arabidopsis enhancer trap lines and have identified 147 lines in which the reporter gene GUS (β-glucuronidase) is expressed in senescing leaves but not in non-senescing ones. We have systematically analyzed the regulation of β-glucuronidase expression in 125 lines (genetically, each contains single T-DNA insertion) by six senescence-promoting factors, namely abscisic acid, ethylene, jasmonic acid, brassinosteroid, darkness, and dehydration. This analysis not only reveals the complexity of the regulatory circuitry but also allows us to postulate the existence of a network of senescence-promoting pathways. We have also cloned three SAGs from randomly selected enhancer trap lines, demonstrating that reporter expression pattern reflects the expression pattern of the endogenous gene. PMID:11402199

20 CFR 229.85 - Substantial gainful activity by blind employee or child.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 20 Employees' Benefits 1 2012-04-01 2012-04-01 false Substantial gainful activity by blind employee or child. 229.85 Section 229.85 Employees' Benefits RAILROAD RETIREMENT BOARD REGULATIONS UNDER... Reductions § 229.85 Substantial gainful activity by blind employee or child. A blind employee or child who is...

20 CFR 229.85 - Substantial gainful activity by blind employee or child.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 20 Employees' Benefits 1 2014-04-01 2012-04-01 true Substantial gainful activity by blind employee or child. 229.85 Section 229.85 Employees' Benefits RAILROAD RETIREMENT BOARD REGULATIONS UNDER THE... § 229.85 Substantial gainful activity by blind employee or child. A blind employee or child who is 55...

20 CFR 229.85 - Substantial gainful activity by blind employee or child.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 20 Employees' Benefits 1 2013-04-01 2012-04-01 true Substantial gainful activity by blind employee or child. 229.85 Section 229.85 Employees' Benefits RAILROAD RETIREMENT BOARD REGULATIONS UNDER THE... § 229.85 Substantial gainful activity by blind employee or child. A blind employee or child who is 55...

FGFR2c-mediated ERK-MAPK activity regulates coronal suture development

PubMed Central

Pfaff, Miles J.; Xue, Ke; Li, Li; Horowitz, Mark C.; Steinbacher, Derek M.; Eswarakumar, Jacob V.P.

2017-01-01

Fibroblast growth factor receptor 2 (FGFR2) signaling is critical for proper craniofacial development. A gain-of-function mutation in the 2c splice variant of the receptor’s gene is associated with Crouzon syndrome, which is characterized by craniosynostosis, the premature fusion of one or more of the cranial vault sutures, leading to craniofacial maldevelopment. Insight into the molecular mechanism of craniosynostosis has identified the ERK-MAPK signaling cascade as a critical regulator of suture patency. The aim of this study is to investigate the role of FGFR2c-induced ERK-MAPK activation in the regulation of coronal suture development. Loss-of-function and gain-of-function Fgfr2c mutant mice have overlapping phenotypes, including coronal synostosis and craniofacial dysmorphia. In vivo analysis of coronal sutures in loss-of-function and gain-of-function models demonstrated fundamentally different pathogenesis underlying coronal suture synostosis. Calvarial osteoblasts from gain-of-function mice demonstrated enhanced osteoblastic function and maturation with concomitant increase in ERK-MAPK activation. In vitro inhibition with the ERK protein inhibitor U0126 mitigated ERK protein activation levels with a concomitant reduction in alkaline phosphatase activity. This study identifies FGFR2c-mediated ERK-MAPK signaling as a key mediator of craniofacial growth and coronal suture development. Furthermore, our results solve the apparent paradox between loss-of-function and gain-of-function FGFR2c mutants with respect to coronal suture synostosis. PMID:27034231

FGFR2c-mediated ERK-MAPK activity regulates coronal suture development.

PubMed

Pfaff, Miles J; Xue, Ke; Li, Li; Horowitz, Mark C; Steinbacher, Derek M; Eswarakumar, Jacob V P

2016-07-15

Fibroblast growth factor receptor 2 (FGFR2) signaling is critical for proper craniofacial development. A gain-of-function mutation in the 2c splice variant of the receptor's gene is associated with Crouzon syndrome, which is characterized by craniosynostosis, the premature fusion of one or more of the cranial vault sutures, leading to craniofacial maldevelopment. Insight into the molecular mechanism of craniosynostosis has identified the ERK-MAPK signaling cascade as a critical regulator of suture patency. The aim of this study is to investigate the role of FGFR2c-induced ERK-MAPK activation in the regulation of coronal suture development. Loss-of-function and gain-of-function Fgfr2c mutant mice have overlapping phenotypes, including coronal synostosis and craniofacial dysmorphia. In vivo analysis of coronal sutures in loss-of-function and gain-of-function models demonstrated fundamentally different pathogenesis underlying coronal suture synostosis. Calvarial osteoblasts from gain-of-function mice demonstrated enhanced osteoblastic function and maturation with concomitant increase in ERK-MAPK activation. In vitro inhibition with the ERK protein inhibitor U0126 mitigated ERK protein activation levels with a concomitant reduction in alkaline phosphatase activity. This study identifies FGFR2c-mediated ERK-MAPK signaling as a key mediator of craniofacial growth and coronal suture development. Furthermore, our results solve the apparent paradox between loss-of-function and gain-of-function FGFR2c mutants with respect to coronal suture synostosis. Copyright © 2016 Elsevier Inc. All rights reserved.

Acute Fasting Regulates Retrograde Synaptic Enhancement through a 4E-BP-Dependent Mechanism.

PubMed

Kauwe, Grant; Tsurudome, Kazuya; Penney, Jay; Mori, Megumi; Gray, Lindsay; Calderon, Mario R; Elazouzzi, Fatima; Chicoine, Nicole; Sonenberg, Nahum; Haghighi, A Pejmun

2016-12-21

While beneficial effects of fasting on organismal function and health are well appreciated, we know little about the molecular details of how fasting influences synaptic function and plasticity. Our genetic and electrophysiological experiments demonstrate that acute fasting blocks retrograde synaptic enhancement that is normally triggered as a result of reduction in postsynaptic receptor function at the Drosophila larval neuromuscular junction (NMJ). This negative regulation critically depends on transcriptional enhancement of eukaryotic initiation factor 4E binding protein (4E-BP) under the control of the transcription factor Forkhead box O (Foxo). Furthermore, our findings indicate that postsynaptic 4E-BP exerts a constitutive negative input, which is counteracted by a positive regulatory input from the Target of Rapamycin (TOR). This combinatorial retrograde signaling plays a key role in regulating synaptic strength. Our results provide a mechanistic insight into how cellular stress and nutritional scarcity could acutely influence synaptic homeostasis and functional stability in neural circuits. Copyright © 2016 Elsevier Inc. All rights reserved.

Littermate presence enhances motor development, weight gain and competitive ability in newborn and juvenile domestic rabbits.

PubMed

Nicolás, Leticia; Martínez-Gómez, Margarita; Hudson, Robyn; Bautista, Amando

2011-01-01

Interest has been growing in the influence siblings may have on individual development. While mammalian research has tended to emphasize competition among siblings for essential but often limited resources such as the mother's milk, there is also evidence of mutual benefits to be had from sibling presence, most notably for altricial young in enhanced thermoregulatory efficiency. In the present study we asked whether littermates of an altricial mammal, the domestic rabbit, might gain other developmental benefits from sibling presence. From postnatal days 1 to 25 we raised rabbit pups either together with their littermates or alone except for the brief, once daily nursing characteristic of this species, while controlling for litter size and ambient nest box temperature. At weaning on Day 25 the young were then transferred to individual cages. Before weaning, we found that pups raised separately from their littermates obtained less milk, and showed lower weight gain and slower development of the ability to maintain body equilibrium than their litter-raised sibs. This was the case even though the two groups did not differ in birth weight or in the ratio of converting milk into body mass in their temperature-controlled nest boxes. Postweaning, the isolation-raised animals were also less successful in competing for food and water when tested after deprivation than their litter-raised sibs. The present study adds to the growing evidence of the influence, in this case positive, that sibs (or half sibs) may have in shaping one another's development. © 2010 Wiley Periodicals, Inc.

Measuring Learning Gain: Comparing Anatomy Drawing Screencasts and Paper-Based Resources

ERIC Educational Resources Information Center

Pickering, James D.

2017-01-01

The use of technology-enhanced learning (TEL) resources is now a common tool across a variety of healthcare programs. Despite this popular approach to curriculum delivery there remains a paucity in empirical evidence that quantifies the change in learning gain. The aim of the study was to measure the changes in learning gain observed with anatomy…

Spatial diversification of agroecosystems to enhance biological control and other regulating services: An agroecological perspective.

PubMed

Hatt, Séverin; Boeraeve, Fanny; Artru, Sidonie; Dufrêne, Marc; Francis, Frédéric

2018-04-15

Spatial diversification of crop and non-crop habitats in farming systems is promising for enhancing natural regulation of insect pests. Nevertheless, results from recent syntheses show variable effects. One explanation is that the abundance and diversity of pests and natural enemies are affected by the composition, design and management of crop and non-crop habitats. Moreover, interactions between both local and landscape elements and practices carried out at different spatial scales may affect the regulation of insect pests. Hence, research is being conducted to understand these interdependencies. However, insects are not the only pests and pests are not the only elements to regulate in agroecosystems. Broadening the scope could allow addressing multiple issues simultaneously, but also solving them together by enhancing synergies. Indeed, spatial diversification of crop and non-crop habitats can allow addressing the issues of weeds and pathogens, along with being beneficial to several other regulating services like pollination, soil conservation and nutrient cycling. Although calls rise to develop multifunctional landscapes that optimize the delivery of multiple ecosystem services, it still represents a scientific challenge today. Enhancing interdisciplinarity in research institutions and building interrelations between scientists and stakeholders may help reach this goal. Despite obstacles, positive results from research based on such innovative approaches are encouraging for engaging science in this path. Hence, the aim of the present paper is to offer an update on these issues by exploring the most recent findings and discussing these results to highlight needs for future research. Copyright © 2017 Elsevier B.V. All rights reserved.

Upregulation of CREB-mediated transcription enhances both short- and long-term memory.

PubMed

Suzuki, Akinobu; Fukushima, Hotaka; Mukawa, Takuya; Toyoda, Hiroki; Wu, Long-Jun; Zhao, Ming-Gao; Xu, Hui; Shang, Yuze; Endoh, Kengo; Iwamoto, Taku; Mamiya, Nori; Okano, Emiko; Hasegawa, Shunsuke; Mercaldo, Valentina; Zhang, Yue; Maeda, Ryouta; Ohta, Miho; Josselyn, Sheena A; Zhuo, Min; Kida, Satoshi

2011-06-15

Unraveling the mechanisms by which the molecular manipulation of genes of interest enhances cognitive function is important to establish genetic therapies for cognitive disorders. Although CREB is thought to positively regulate formation of long-term memory (LTM), gain-of-function effects of CREB remain poorly understood, especially at the behavioral level. To address this, we generated four lines of transgenic mice expressing dominant active CREB mutants (CREB-Y134F or CREB-DIEDML) in the forebrain that exhibited moderate upregulation of CREB activity. These transgenic lines improved not only LTM but also long-lasting long-term potentiation in the CA1 area in the hippocampus. However, we also observed enhanced short-term memory (STM) in contextual fear-conditioning and social recognition tasks. Enhanced LTM and STM could be dissociated behaviorally in these four lines of transgenic mice, suggesting that the underlying mechanism for enhanced STM and LTM are distinct. LTM enhancement seems to be attributable to the improvement of memory consolidation by the upregulation of CREB transcriptional activity, whereas higher basal levels of BDNF, a CREB target gene, predicted enhanced shorter-term memory. The importance of BDNF in STM was verified by microinfusing BDNF or BDNF inhibitors into the hippocampus of wild-type or transgenic mice. Additionally, increasing BDNF further enhanced LTM in one of the lines of transgenic mice that displayed a normal BDNF level but enhanced LTM, suggesting that upregulation of BDNF and CREB activity cooperatively enhances LTM formation. Our findings suggest that CREB positively regulates memory consolidation and affects memory performance by regulating BDNF expression.

Enhanced synthesis and release of dopamine in transgenic mice with gain-of-function α6* nAChRs.

PubMed

Wang, Yuexiang; Lee, Jang-Won; Oh, Gyeon; Grady, Sharon R; McIntosh, J Michael; Brunzell, Darlene H; Cannon, Jason R; Drenan, Ryan M

2014-04-01

α6β2* nicotinic acetylcholine receptors (nAChRs)s in the ventral tegmental area to nucleus accumbens (NAc) pathway are implicated in the response to nicotine, and recent work suggests these receptors play a role in the rewarding action of ethanol. Here, we studied mice expressing gain-of-function α6β2* nAChRs (α6L9'S mice) that are hypersensitive to nicotine and endogenous acetylcholine. Evoked extracellular dopamine (DA) levels were enhanced in α6L9'S NAc slices compared to control, non-transgenic (non-Tg) slices. Extracellular DA levels in both non-Tg and α6L9'S slices were further enhanced in the presence of GBR12909, suggesting intact DA transporter function in both mouse strains. Ongoing α6β2* nAChR activation by acetylcholine plays a role in enhancing DA levels, as α-conotoxin MII completely abolished evoked DA release in α6L9'S slices and decreased spontaneous DA release from striatal synaptosomes. In HPLC experiments, α6L9'S NAc tissue contained significantly more DA, 3,4-dihydroxyphenylacetic acid, and homovanillic acid compared to non-Tg NAc tissue. Serotonin (5-HT), 5-hydroxyindoleacetic acid, and norepinephrine (NE) were unchanged in α6L9'S compared to non-Tg tissue. Western blot analysis revealed increased tyrosine hydroxylase expression in α6L9'S NAc. Overall, these results show that enhanced α6β2* nAChR activity in NAc can stimulate DA production and lead to increased extracellular DA levels. © 2013 International Society for Neurochemistry.

Introductory Biology Students’ Use of Enhanced Answer Keys and Reflection Questions to Engage in Metacognition and Enhance Understanding

PubMed Central

Sabel, Jaime L.; Dauer, Joseph T.; Forbes, Cory T.

2017-01-01

Providing feedback to students as they learn to integrate individual concepts into complex systems is an important way to help them to develop robust understanding, but it is challenging in large, undergraduate classes for instructors to provide feedback that is frequent and directed enough to help individual students. Various scaffolds can be used to help students engage in self-regulated learning and generate internal feedback to improve their learning. This study examined the use of enhanced answer keys with added reflection questions and instruction as scaffolds for engaging undergraduate students in self-regulated learning within an introductory biology course. Study findings show that both the enhanced answer keys and reflection questions helped students to engage in metacognition and develop greater understanding of biological concepts. Further, students who received additional instruction on the use of the scaffolds changed how they used them and, by the end of the semester, were using the scaffolds in significantly different ways and showed significantly higher learning gains than students who did not receive the instruction. These findings provide evidence for the benefit of designing scaffolds within biology courses that will support students in engaging in metacognition and enhancing their understanding of biological concepts. PMID:28645893

Self-Regulated Learning in Technology Enhanced Learning Environments: An Investigation with University Students

ERIC Educational Resources Information Center

Lenne, Dominique; Abel, Marie-Helene; Trigano, Philippe; Leblanc, Adeline

2008-01-01

In Technology Enhanced Learning Environments, self-regulated learning (SRL) partly relies on the features of the technological tools. The authors present two environments they designed in order to facilitate SRL: the first one (e-Dalgo) is a website dedicated to the learning of algorithms and computer programming. It is structured as a classical…

The CGTCA sequence motif is essential for biological activity of the vasoactive intestinal peptide gene cAMP-regulated enhancer.

PubMed Central

Fink, J S; Verhave, M; Kasper, S; Tsukada, T; Mandel, G; Goodman, R H

1988-01-01

cAMP-regulated transcription of the human vasoactive intestinal peptide gene is dependent upon a 17-base-pair DNA element located 70 base pairs upstream from the transcriptional initiation site. This element is similar to sequences in other genes known to be regulated by cAMP and to sequences in several viral enhancers. We have demonstrated that the vasoactive intestinal peptide regulatory element is an enhancer that depends upon the integrity of two CGTCA sequence motifs for biological activity. Mutations in either of the CGTCA motifs diminish the ability of the element to respond to cAMP. Enhancers containing the CGTCA motif from the somatostatin and adenovirus genes compete for binding of nuclear proteins from C6 glioma and PC12 cells to the vasoactive intestinal peptide enhancer, suggesting that CGTCA-containing enhancers interact with similar transacting factors. Images PMID:2842787

Transcription regulation by distal enhancers

PubMed Central

Stadhouders, Ralph; van den Heuvel, Anita; Kolovos, Petros; Jorna, Ruud; Leslie, Kris; Grosveld, Frank; Soler, Eric

2012-01-01

Genome-wide chromatin profiling efforts have shown that enhancers are often located at large distances from gene promoters within the noncoding genome. Whereas enhancers can stimulate transcription initiation by communicating with promoters via chromatin looping mechanisms, we propose that enhancers may also stimulate transcription elongation by physical interactions with intronic elements. We review here recent findings derived from the study of the hematopoietic system. PMID:22771987

Intensity fluctuations in bimodal micropillar lasers enhanced by quantum-dot gain competition

NASA Astrophysics Data System (ADS)

Leymann, H. A. M.; Hopfmann, C.; Albert, F.; Foerster, A.; Khanbekyan, M.; Schneider, C.; Höfling, S.; Forchel, A.; Kamp, M.; Wiersig, J.; Reitzenstein, S.

2013-05-01

We investigate correlations between orthogonally polarized cavity modes of a bimodal micropillar laser with a single layer of self-assembled quantum dots in the active region. While one emission mode of the microlaser demonstrates a characteristic S-shaped input-output curve, the output intensity of the second mode saturates and even decreases with increasing injection current above threshold. Measuring the photon autocorrelation function g(2)(τ) of the light emission confirms the onset of lasing in the first mode with g(2)(0) approaching unity above threshold. In contrast, strong photon bunching associated with superthermal values of g(2)(0) is detected for the other mode for currents above threshold. This behavior is attributed to gain competition of the two modes induced by the common gain material, which is confirmed by photon cross-correlation measurements revealing a clear anticorrelation between emission events of the two modes. The experimental studies are in qualitative agreement with theoretical studies based on a microscopic semiconductor theory, which we extend to the case of two modes interacting with the common gain medium. Moreover, we treat the problem by a phenomenological birth-death model extended to two interacting modes, which reveals that the photon probability distribution of each mode has a double-peak structure, indicating switching behavior of the modes for pump rates around threshold.

Coordinated regulation of IFITM1, 2 and 3 genes by an IFN-responsive enhancer through long-range chromatin interactions.

PubMed

Li, Ping; Shi, Ming-Lei; Shen, Wen-Long; Zhang, Zhang; Xie, De-Jian; Zhang, Xiang-Yuan; He, Chao; Zhang, Yan; Zhao, Zhi-Hu

2017-08-01

Interferon-induced transmembrane protein (IFITM) 1, 2 and 3 genes encode a family of interferon (IFN)-induced transmembrane proteins that block entry of a broad spectrum of pathogens. However, the transcriptional regulation of these genes, especially whether there exist any enhancers and their roles during the IFN induction process remain elusive. Here, through public data mining, episomal luciferase reporter assay and in vivo CRISPR-Cas9 genome editing, we identified an IFN-responsive enhancer located 35kb upstream of IFITM3 gene promoter upregulating the IFN-induced expression of IFITM1, 2 and 3 genes. Chromatin immunoprecipitation (ChIP), electrophoretic mobility shift assay (EMSA) and luciferase reporter assay demonstrated that signal transducers and activators of transcription (STAT) 1 bound to the enhancer with the treatment of IFN and was indispensable for the enhancer activity. Furthermore, using chromosome conformation capture technique, we revealed that the IFITM1, 2 and 3 genes physically clustered together and constitutively looped to the distal enhancer through long-range interactions in both HEK293 and A549 cells, providing structural basis for coordinated regulation of IFITM1, 2 and 3 by the enhancer. Finally, we showed that in vivo truncation of the enhancer impaired IFN-induced resistance to influenza A virus (IAV) infection. These findings expand our understanding of the mechanisms underlying the transcriptional regulation of IFITM1, 2 and 3 expression and its ability to mediate IFN signaling. Copyright © 2017 Elsevier B.V. All rights reserved.

Endothelial cell SHP-2 negatively regulates neutrophil adhesion and promotes transmigration by enhancing ICAM-1-VE-cadherin interaction.

PubMed

Yan, Meiping; Zhang, Xinhua; Chen, Ao; Gu, Wei; Liu, Jie; Ren, Xiaojiao; Zhang, Jianping; Wu, Xiaoxiong; Place, Aaron T; Minshall, Richard D; Liu, Guoquan

2017-11-01

Intercellular adhesion molecule-1 (ICAM-1) mediates the firm adhesion of leukocytes to endothelial cells and initiates subsequent signaling that promotes their transendothelial migration (TEM). Vascular endothelial (VE)-cadherin plays a critical role in endothelial cell-cell adhesion, thereby controlling endothelial permeability and leukocyte transmigration. This study aimed to determine the molecular signaling events that originate from the ICAM-1-mediated firm adhesion of neutrophils that regulate VE-cadherin's role as a negative regulator of leukocyte transmigration. We observed that ICAM-1 interacts with Src homology domain 2-containing phosphatase-2 (SHP-2), and SHP-2 down-regulation via silencing of small interfering RNA in endothelial cells enhanced neutrophil adhesion to endothelial cells but inhibited neutrophil transmigration. We also found that VE-cadherin associated with the ICAM-1-SHP-2 complex. Moreover, whereas the activation of ICAM-1 leads to VE-cadherin dissociation from ICAM-1 and VE-cadherin association with actin, SHP-2 down-regulation prevented ICAM-1-VE-cadherin association and promoted VE-cadherin-actin association. Furthermore, SHP-2 down-regulation in vivo promoted LPS-induced neutrophil recruitment in mouse lung but delayed neutrophil extravasation. These results suggest that SHP-2- via association with ICAM-1-mediates ICAM-1-induced Src activation and modulates VE-cadherin switching association with ICAM-1 or actin, thereby negatively regulating neutrophil adhesion to endothelial cells and enhancing their TEM.-Yan, M., Zhang, X., Chen, A., Gu, W., Liu, J., Ren, X., Zhang, J., Wu, X., Place, A. T., Minshall, R. D., Liu, G. Endothelial cell SHP-2 negatively regulates neutrophil adhesion and promotes transmigration by enhancing ICAM-1-VE-cadherin interaction. © FASEB.

Gestational Weight Gain: Results from the Delta Healthy Sprouts Comparative Impact Trial.

PubMed

Thomson, Jessica L; Tussing-Humphreys, Lisa M; Goodman, Melissa H; Olender, Sarah E

2016-01-01

Introduction. Delta Healthy Sprouts trial was designed to test the comparative impact of two home visiting programs on weight status, dietary intake, and health behaviors of Southern African American women and their infants. Results pertaining to the primary outcome, gestational weight gain, are reported. Methods. Participants (n = 82), enrolled early in their second trimester of pregnancy, were randomly assigned to one of two treatment arms. Gestational weight gain, measured at six monthly home visits, was calculated by subtracting measured weight at each visit from self-reported prepregnancy weight. Weight gain was classified as under, within, or exceeding the Institute of Medicine recommendations based on prepregnancy body mass index. Chi-square tests and generalized linear mixed models were used to test for significant differences in percentages of participants within recommended weight gain ranges. Results. Differences in percentages of participants within the gestational weight gain guidelines were not significant between treatment arms across all visits. Conclusions. Enhancing the gestational nutrition and physical activity components of an existing home visiting program is feasible in a high risk population of primarily low income African American women. The impact of these enhancements on appropriate gestational weight gain is questionable given the more basic living needs of such women. This trial is registered with ClinicalTrials.gov NCT01746394, registered 4 December 2012.

Active and Inactive Enhancers Cooperate to Exert Localized and Long-Range Control of Gene Regulation.

PubMed

Proudhon, Charlotte; Snetkova, Valentina; Raviram, Ramya; Lobry, Camille; Badri, Sana; Jiang, Tingting; Hao, Bingtao; Trimarchi, Thomas; Kluger, Yuval; Aifantis, Iannis; Bonneau, Richard; Skok, Jane A

2016-06-07

V(D)J recombination relies on the presence of proximal enhancers that activate the antigen receptor (AgR) loci in a lineage- and stage-specific manner. Unexpectedly, we find that both active and inactive AgR enhancers cooperate to disseminate their effects in a localized and long-range manner. Here, we demonstrate the importance of short-range contacts between active enhancers that constitute an Igk super-enhancer in B cells. Deletion of one element reduces the interaction frequency between other enhancers in the hub, which compromises the transcriptional output of each component. Furthermore, we establish that, in T cells, long-range contact and cooperation between the inactive Igk enhancer MiEκ and the active Tcrb enhancer Eβ alters enrichment of CBFβ binding in a manner that impacts Tcrb recombination. These findings underline the complexities of enhancer regulation and point to a role for localized and long-range enhancer-sharing between active and inactive elements in lineage- and stage-specific control. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Regulating the dorsal neural tube expression of Ptf1a through a distal 3' enhancer.

PubMed

Mona, Bishakha; Avila, John M; Meredith, David M; Kollipara, Rahul K; Johnson, Jane E

2016-10-01

Generating the correct balance of inhibitory and excitatory neurons in a neural network is essential for normal functioning of a nervous system. The neural network in the dorsal spinal cord functions in somatosensation where it modulates and relays sensory information from the periphery. PTF1A is a key transcriptional regulator present in a specific subset of neural progenitor cells in the dorsal spinal cord, cerebellum and retina that functions to specify an inhibitory neuronal fate while suppressing excitatory neuronal fates. Thus, the regulation of Ptf1a expression is critical for determining mechanisms controlling neuronal diversity in these regions of the nervous system. Here we identify a sequence conserved, tissue-specific enhancer located 10.8kb 3' of the Ptf1a coding region that is sufficient to direct expression to dorsal neural tube progenitors that give rise to neurons in the dorsal spinal cord in chick and mouse. DNA binding motifs for Paired homeodomain (Pd-HD) and zinc finger (ZF) transcription factors are required for enhancer activity. Mutations in these sequences implicate the Pd-HD motif for activator function and the ZF motif for repressor function. Although no repressor transcription factor was identified, both PAX6 and SOX3 can increase enhancer activity in reporter assays. Thus, Ptf1a is regulated by active and repressive inputs integrated through multiple sequence elements within a highly conserved sequence downstream of the Ptf1a gene. Copyright © 2016 Elsevier Inc. All rights reserved.

A gain and bandwidth enhanced transimpedance preamplifier for Fourier-transform ion cyclotron resonance mass spectrometry

NASA Astrophysics Data System (ADS)

Lin, Tzu-Yung; Green, Roger J.; O'Connor, Peter B.

2011-12-01

The nature of the ion signal from a 12-T Fourier-transform ion cyclotron resonance mass spectrometer and the electronic noise were studied to further understand the electronic detection limit. At minimal cost, a new transimpedance preamplifier was designed, computer simulated, built, and tested. The preamplifier design pushes the electronic signal-to-noise performance at room temperature to the limit, because of its enhanced tolerance of the capacitance of the detection device, lower intrinsic noise, and larger flat mid-band gain (input current noise spectral density of around 1 pA/sqrt{Hz} when the transimpedance is about 85 dBΩ). The designed preamplifier has a bandwidth of ˜3 kHz to 10 MHz, which corresponds to the mass-to-charge ratio, m/z, of approximately 18 to 61 k at 12 T. The transimpedance and the bandwidth can be easily adjusted by changing the value of passive components. The feedback limitation of the circuit is discussed. With the maximum possible transimpedance of 5.3 MΩ when using an 0402 surface mount resistor, the preamplifier was estimated to be able to detect ˜110 charges in a single scan.

A gain and bandwidth enhanced transimpedance preamplifier for Fourier-transform ion cyclotron resonance mass spectrometry

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

Lin, Tzu-Yung; Green, Roger J.; O'Connor, Peter B.

2011-12-15

The nature of the ion signal from a 12-T Fourier-transform ion cyclotron resonance mass spectrometer and the electronic noise were studied to further understand the electronic detection limit. At minimal cost, a new transimpedance preamplifier was designed, computer simulated, built, and tested. The preamplifier design pushes the electronic signal-to-noise performance at room temperature to the limit, because of its enhanced tolerance of the capacitance of the detection device, lower intrinsic noise, and larger flat mid-band gain (input current noise spectral density of around 1 pA/{radical}(Hz) when the transimpedance is about 85 dB{Omega}). The designed preamplifier has a bandwidth of {approx}3more » kHz to 10 MHz, which corresponds to the mass-to-charge ratio, m/z, of approximately 18 to 61 k at 12 T. The transimpedance and the bandwidth can be easily adjusted by changing the value of passive components. The feedback limitation of the circuit is discussed. With the maximum possible transimpedance of 5.3 M{Omega} when using an 0402 surface mount resistor, the preamplifier was estimated to be able to detect {approx}110 charges in a single scan.« less

Active and inactive enhancers co-operate to exert localized and long-range control of gene regulation

PubMed Central

Proudhon, Charlotte; Snetkova, Valentina; Raviram, Ramya; Lobry, Camille; Badri, Sana; Jiang, Tingting; Hao, Bingtao; Trimarchi, Thomas; Kluger, Yuval; Aifantis, Iannis; Bonneau, Richard; Skok, Jane A

2016-01-01

V(D)J recombination relies on the presence of proximal enhancers that activate the antigen receptor (AgR) loci in a lineage and stage specific manner. Unexpectedly we find that both active and inactive AgR enhancers co-operate to disseminate their effects in a localized and long-range manner. Here we demonstrate the importance of short-range contacts between active enhancers that constitute an Igk super-enhancer in B cells. Deletion of one element reduces the interaction frequency between other enhancers in the hub, which compromises the transcriptional output of each component. We further establish that in T cells long-range contact and co-operation between the inactive Igk enhancer, MiEκ and the active Tcrb enhancer, Eβ, alters enrichment of CBFβ binding in a manner that impacts Tcrb recombination. These findings underline the complexities of enhancer regulation and point to a role for localized and long-range enhancer-sharing between active and inactive elements in lineage and stage specific control. PMID:27239026

Does Using E-Portfolios for Reflective Writing Enhance High School Students' Self-Regulated Learning?

ERIC Educational Resources Information Center

Chang, Chi-Cheng; Liang, Chaoyun; Shu, Kuen-Ming; Tseng, Kuo-Hung; Lin, Chun-Yu

2016-01-01

The study aims to examine whether reflective writing using e-portfolios enhances high school students' self-regulated learning. Participants included two classes of eighth-graders majoring in Information Processing and taking a course called "Website Design" at a vocational high school in Taiwan. There were 41 students, with 18 males and…

Biodegradable Hollow Mesoporous Silica Nanoparticles for Regulating Tumor Microenvironment and Enhancing Antitumor Efficiency

PubMed Central

Kong, Miao; Tang, Jiamin; Qiao, Qi; Wu, Tingting; Qi, Yan; Tan, Songwei; Gao, Xueqin; Zhang, Zhiping

2017-01-01

There is accumulating evidence that regulating tumor microenvironment plays a vital role in improving antitumor efficiency. Herein, to remodel tumor immune microenvironment and elicit synergistic antitumor effects, lipid-coated biodegradable hollow mesoporous silica nanoparticle (dHMLB) was constructed with co-encapsulation of all-trans retinoic acid (ATRA), doxorubicin (DOX) and interleukin-2 (IL-2) for chemo-immunotherapy. The nanoparticle-mediated combinational therapy provided a benign regulation on tumor microenvironment through activation of tumor infiltrating T lymphocytes and natural killer cells, promotion of cytokines secretion of IFN-γ and IL-12, and down-regulation of immunosuppressive myeloid-derived suppressor cells, cytokine IL-10 and TGF-β. ATRA/DOX/IL-2 co-loaded dHMLB demonstrated significant tumor growth and metastasis inhibition, and also exhibited favorable biodegradability and safety. This nanoplatform has great potential in developing a feasible strategy to remodel tumor immune microenvironment and achieve enhanced antitumor effect. PMID:28900509

Mediator complex dependent regulation of cardiac development and disease.

PubMed

Grueter, Chad E

2013-06-01

Cardiovascular disease (CVD) is a leading cause of morbidity and mortality. The risk factors for CVD include environmental and genetic components. Human mutations in genes involved in most aspects of cardiovascular function have been identified, many of which are involved in transcriptional regulation. The Mediator complex serves as a pivotal transcriptional regulator that functions to integrate diverse cellular signals by multiple mechanisms including recruiting RNA polymerase II, chromatin modifying proteins and non-coding RNAs to promoters in a context dependent manner. This review discusses components of the Mediator complex and the contribution of the Mediator complex to normal and pathological cardiac development and function. Enhanced understanding of the role of this core transcriptional regulatory complex in the heart will help us gain further insights into CVD. Copyright © 2013. Production and hosting by Elsevier Ltd.

Enzymological mechanism for the regulation of lanthanum chloride on flavonoid synthesis of soybean seedlings under enhanced ultraviolet-B radiation.

PubMed

Fan, Caixia; Hu, Huiqing; Wang, Lihong; Zhou, Qing; Huang, Xiaohua

2014-01-01

In order to probe into the enzymological mechanism for the regulation of lanthanum chloride (LaCl3) on flavonoid synthesis in plants under enhanced ultraviolet-B (UV-B) radiation, the effects of LaCl₃ (20 and 60 mg l(-1)) on the content of flavonoids as well as the activities of phenylalanine ammonia-lyase (PAL), cinnamate-4-hydroxylase (C4H), 4-coumarate : coenzyme A ligase (4CL), and chalcone synthase (CHS) in soybean seedlings under enhanced UV-B radiation (2.6 and 6.2 kJ m(-2) day(-1)) were investigated. Enhanced UV-B radiation (2.6 and 6.2 kJ m(-2) day(-1)) caused the increase in the content of flavonoids as well as the activities of PAL, C4H, 4CL, and CHS in soybean seedlings. The treatment of 20 mg l(-1) LaCl₃ also efficiently increased these indices, which promoted the flavonoid synthesis and provided protective effects for resisting enhanced UV-B radiation. On the contrary, the treatment of 60 mg l(-1) LaCl₃ decreased the content of flavonoids as well as the activities of C4H, 4CL, and CHS in soybean seedlings except increasing the activity of PAL, which were not beneficial to the flavonoid synthesis and provided negative effects for resisting enhanced UV-B radiation. In conclusion, enhanced UV-B radiation caused the increase in the flavonoid synthesis by promoting the activities of PAL, C4H, 4CL, and CHS in soybean seedlings. The treatment of LaCl₃ could change flavonoid synthesis in soybean seedlings under enhanced UV-B radiation by regulating the activities of PAL, C4H, 4CL, and CHS, which is an enzymological mechanism for the regulation of LaCl₃ on flavonoid synthesis in plants under enhanced UV-B radiation.

Gain Scheduling for the Orion Launch Abort Vehicle Controller

NASA Technical Reports Server (NTRS)

McNamara, Sara J.; Restrepo, Carolina I.; Madsen, Jennifer M.; Medina, Edgar A.; Proud, Ryan W.; Whitley, Ryan J.

2011-01-01

One of NASAs challenges for the Orion vehicle is the control system design for the Launch Abort Vehicle (LAV), which is required to abort safely at any time during the atmospheric ascent portion of ight. The focus of this paper is the gain design and scheduling process for a controller that covers the wide range of vehicle configurations and flight conditions experienced during the full envelope of potential abort trajectories from the pad to exo-atmospheric flight. Several factors are taken into account in the automation process for tuning the gains including the abort effectors, the environmental changes and the autopilot modes. Gain scheduling is accomplished using a linear quadratic regulator (LQR) approach for the decoupled, simplified linear model throughout the operational envelope in time, altitude and Mach number. The derived gains are then implemented into the full linear model for controller requirement validation. Finally, the gains are tested and evaluated in a non-linear simulation using the vehicles ight software to ensure performance requirements are met. An overview of the LAV controller design and a description of the linear plant models are presented. Examples of the most significant challenges with the automation of the gain tuning process are then discussed. In conclusion, the paper will consider the lessons learned through out the process, especially in regards to automation, and examine the usefulness of the gain scheduling tool and process developed as applicable to non-Orion vehicles.

Weight-gain misperceptions and the third-person effect in Black and White college-bound females: potential implications for healthy weight management.

PubMed

Webb, Jennifer B; Butler-Ajibade, Phoebe; Robinson, Seronda A; Lee, Shanique J

2013-08-01

Elements of social norm theory and communication theory on the third-person effect may prove useful in efforts to prevent excessive weight gain among emerging adults entering college. The present study explored the associations of race/ethnicity and BMI status with these socio-cognitive factors that may affect first-year weight regulation in a sample of Black (N = 247) and White (N = 94) college-bound females. Participants completed an online survey assessing first-year weight-gain perceived norms along with weight-change expectations and concerns. Results provided evidence of the persistence of the myth of the "Freshman 15", belief in the typicality of gaining weight during the first year of college, and significant concern about first-year weight gain. Initial findings further revealed a robust third-person effect whereby despite nearly 90% of the sample endorsing that first-year weight gain was common, only 12% expected they would experience weight gain. Main effects of race/ethnicity, BMI status, and their interaction further uncovered distinct patterns of findings. Preliminary results highlight the need for college health officials at both predominantly White as well as minority-serving institutions to adequately address the significant concern over first-year weight gain in conjunction with the desire to lose weight expressed by an appreciable number of incoming college females. Findings also advocate the utility of evaluating social norm theory and the third-person perceptual bias in the context of first-year weight gain to potentially enhance the design and effectiveness of healthy weight management initiatives among ethnically-diverse young women entering college. Copyright © 2013 Elsevier Ltd. All rights reserved.

Cis-regulation of the amphioxus engrailed gene: insights into evolution of a muscle-specific enhancer.

PubMed

Beaster-Jones, Laura; Schubert, Michael; Holland, Linda Z

2007-08-01

To gain insights into the relation between evolution of cis-regulatory DNA and evolution of gene function, we identified tissue-specific enhancers of the engrailed gene of the basal chordate amphioxus (Branchiostoma floridae) and compared their ability to direct expression in both amphioxus and its nearest chordate relative, the tunicate Ciona intestinalis. In amphioxus embryos, the native engrailed gene is expressed in three domains - the eight most anterior somites, a few cells in the central nervous system (CNS) and a few ectodermal cells. In contrast, in C. intestinalis, in which muscle development is highly divergent, engrailed expression is limited to the CNS. To characterize the tissue-specific enhancers of amphioxus engrailed, we first showed that 7.8kb of upstream DNA of amphioxus engrailed directs expression to all three domains in amphioxus that express the native gene. We then identified the amphioxus engrailed muscle-specific enhancer as the 1.2kb region of upstream DNA with the highest sequence identity to the mouse en-2 jaw muscle enhancer. This amphioxus enhancer directed expression to both the somites in amphioxus and to the larval muscles in C. intestinalis. These results show that even though expression of the native engrailed has apparently been lost in developing C. intestinalis muscles, they express the transcription factors necessary to activate transcription from the amphioxus engrailed enhancer, suggesting that gene networks may not be completely disrupted if an individual component is lost.

An ultra-low power output capacitor-less low-dropout regulator with slew-rate-enhanced circuit

NASA Astrophysics Data System (ADS)

Cheng, Xin; Zhang, Yu; Xie, Guangjun; Yang, Yizhong; Zhang, Zhang

2018-03-01

An ultra-low power output-capacitorless low-dropout (LDO) regulator with a slew-rate-enhanced (SRE) circuit is introduced. The increased slew rate is achieved by sensing the transient output voltage of the LDO and then charging (or discharging) the gate capacitor quickly. In addition, a buffer with ultra-low output impedance is presented to improve line and load regulations. This design is fabricated by SMIC 0.18 μm CMOS technology. Experimental results show that, the proposed LDO regulator only consumes an ultra-low quiescent current of 1.2 μA. The output current range is from 10 μA to 200 mA and the corresponding variation of output voltage is less than 40 mV. Moreover, the measured line regulation and load regulation are 15.38 mV/V and 0.4 mV/mA respectively. Project supported by the National Natural Science Foundation of China (Nos. 61401137, 61404043, 61674049).

PTH 1-34 Ameliorates the Osteopenia and Delayed Healing of Stabilized Tibia Fracture in Mice with Achondroplasia Resulting from Gain-Of-Function Mutation of FGFR3

PubMed Central

Chen, Hangang; Sun, Xianding; Yin, Liangjun; Chen, Shuai; Zhu, Ying; Huang, Junlan; Jiang, Wanling; Chen, Bo; Zhang, Ruobin; Chen, Lin; Nie, Mao; Xie, Yangli; Deng, Zhongliang

2017-01-01

Bone fracture healing is processed through multiple stages including the cartilaginous callus formation and its transition to bony callus. FGFR3 negatively regulates chondrogenesis and enhances osteogenesis during skeleton development. We previously found in mice carrying gain-of-function mutation of FGFR3 that FGFR3 delays the healing of un-stabilized fracture that heals mainly through endochondral ossification. Since fracture is regularly treated in clinics with rigid fixation, and stabilized fracture is healed largely through intramembranous ossification, we asked whether FGFR3, a key regulator of osteogenesis, also affect the regeneration of stabilized fracture. We found that gain-of-function mutation of FGFR3 inhibits the initiation of chondrogenesis and the subsequent bone formation. We further studied whether PTH1-34 can improve the osteopenia and delayed healing of the stabilized tibia fracture in mice with achondroplasia. Fracture healing was evaluated by radiography, micro-CT, biomechanical tests, histology, and real-time polymerase chain reaction (RT-PCR) analysis. We found that PTH 1-34 can alleviate the decreased bone mass and compromised architecture in ACH mice. Histological analysis revealed that administration of PTH1-34 increased the size of both the total callus and cartilaginous callus at 14 days after the surgery in ACH mice. RT-PCR data suggested that systemic PTH1-34 accelerated the initiation of chondrogenesis and chondrocyte maturation (earlier and higher levels of expression of chondrogenesis related markers) and enhanced the osteogenic differentiation in the fracture callus in ACH mice. These results indicate that the PTH1-34 administration resulted in an enhanced callus formation during bone fracture healing in ACH mice, which is at least in part mediated by an increase of cartilaginous callus at early stage and the promotion of bone formation in bony callus. In summary, in this study we revealed that FGFR3 delays the regeneration of

Optical gain in an optically driven three-level ? system in atomic Rb vapor

NASA Astrophysics Data System (ADS)

Ballmann, C. W.; Yakovlev, V. V.

2018-06-01

In this work, we report experimentally achieved optical gain of a weak probe beam in a three-level ? system in a low density Rubidium vapor cell driven by a single pump beam. The maximum measured gain of the probe beam was about 0.12%. This work could lead to new approaches for enhancing molecular spectroscopy applications.

GABAergic Neural Activity Involved in Salicylate-Induced Auditory Cortex Gain Enhancement

PubMed Central

Lu, Jianzhong; Lobarinas, Edward; Deng, Anchun; Goodey, Ronald; Stolzberg, Daniel; Salvi, Richard J.; Sun, Wei

2011-01-01

Although high doses of sodium salicylate impair cochlear function, it paradoxically enhances sound-evoked activity in the auditory cortex (AC) and augments acoustic startle reflex responses, neural and behavioral metrics associated with hyperexcitability and hyperacusis. To explore the neural mechanisms underlying salicylate-induced hyperexcitability and “increased central gain”, we examined the effects of γ-aminobutyric acid (GABA) receptor agonists and antagonists on salicylate-induced hyperexcitability in the AC and startle reflex responses. Consistent with our previous findings, local or systemic application of salicylate significantly increased the amplitude of sound-evoked AC neural activity, but generally reduced spontaneous activity in the AC. Systemic injection of salicylate also significantly increased the acoustic startle reflex. S-baclofen or R-baclofen, GABA-B agonists, which suppressed sound-evoked AC neural firing rate and local field potentials, also suppressed the salicylate-induced enhancement of the AC field potential and the acoustic startle reflex. Local application of vigabatrin, which enhances GABA concentration in the brain, suppressed the salicylate-induced enhancement of AC firing rate. Systemic injection of vigabatrin also reduced the salicylate-induced enhancement of acoustic startle reflex. Collectively, these results suggest that the sound-evoked behavioral and neural hyperactivity induced by salicylate may arise from a salicylate-induced suppression GABAergic inhibition in the AC. PMID:21664433

Combinatorial regulation of a Blimp1 (Prdm1) enhancer in the mouse retina

PubMed Central

Mills, Taylor S.; Eliseeva, Tatiana; Bersie, Stephanie M.; Randazzo, Grace; Nahreini, Jhenya; Park, Ko Uoon

2017-01-01

The mouse retina comprises seven major cell types that exist in differing proportions. They are generated from multipotent progenitors in a stochastic manner, such that the relative frequency of any given type generated changes over time. The mechanisms determining the proportions of each cell type are only partially understood. Photoreceptors and bipolar interneurons are derived from cells that express Otx2. Within this population, Blimp1 (Prdm1) helps set the balance between photoreceptors and bipolar cells by suppressing bipolar identity in most of the cells. How only a subset of these Otx2+ cells decides to upregulate Blimp1 and adopt photoreceptor fate is unknown. To understand this, we investigated how Blimp1 transcription is regulated. We identified several potential Blimp1 retinal enhancer elements using DNase hypersensitivity sequencing. Only one of the elements recapitulated Blimp1 spatial and temporal expression in cultured explant assays and within the retinas of transgenic mice. Mutagenesis of this retinal Blimp1 enhancer element revealed four discrete sequences that were each required for its activity. These included highly conserved Otx2 and ROR (retinoic acid receptor related orphan receptor) binding sites. The other required sequences do not appear to be controlled by Otx2 or ROR factors, increasing the complexity of the Blimp1 gene regulatory network. Our results show that the intersection of three or more transcription factors is required to correctly regulate the spatial and temporal features of Blimp1 enhancer expression. This explains how Blimp1 expression can diverge from Otx2 and set the balance between photoreceptor and bipolar fates. PMID:28829770

Weight gain by gut microbiota manipulation in productive animals.

PubMed

Angelakis, Emmanouil

2017-05-01

Antibiotics, prebiotics and probiotics are widely used as growth promoters in agriculture. In the 1940s, use of Streptomyces aureofaciens probiotics resulted in weight gain in animals, which led to the discovery of chlortetracycline. Tetracyclines, macrolides, avoparcin and penicillins have been commonly used in livestock agriculture to promote growth through increased food intake, weight gain, and improved herd health. Prebiotic supplements including oligosaccharides, fructooligosaccharides, and galactosyl-lactose improve the growth performance of animals. Probiotics used in animal feed are mainly bacterial strains of Gram-positive bacteria and have been effectively used for weight gain in chickens, pigs, ruminants and in aquaculture. Antibiotics, prebiotics and probiotics all modify the gut microbiota and the effect of a probiotic species on the digestive flora is probably determined by bacteriocin production. Regulations governing the introduction of novel probiotics and prebiotics vary by geographical region and bias is very common in industry-funded studies. Probiotic and prebiotic foods have been consumed for centuries, either as natural components of food, or as fermented foods and it is possible to cause the same weight gain effects in humans as in animals. This review presents the use of growth promoters in food-producing animals to influence food intake and weight gain. Copyright © 2016 Elsevier Ltd. All rights reserved.

A gain and bandwidth enhanced transimpedance preamplifier for Fourier-transform ion cyclotron resonance mass spectrometry

PubMed Central

Lin, Tzu-Yung; Green, Roger J.; O'Connor, Peter B.

2011-01-01

The nature of the ion signal from a 12-T Fourier-transform ion cyclotron resonance mass spectrometer and the electronic noise were studied to further understand the electronic detection limit. At minimal cost, a new transimpedance preamplifier was designed, computer simulated, built, and tested. The preamplifier design pushes the electronic signal-to-noise performance at room temperature to the limit, because of its enhanced tolerance of the capacitance of the detection device, lower intrinsic noise, and larger flat mid-band gain (input current noise spectral density of around 1 pA/\\documentclass[12pt]{minimal}\\begin{document}$\\sqrt{\\mbox{Hz}}$\\end{document}Hz when the transimpedance is about 85 dBΩ). The designed preamplifier has a bandwidth of ∼3 kHz to 10 MHz, which corresponds to the mass-to-charge ratio, m/z, of approximately 18 to 61 k at 12 T. The transimpedance and the bandwidth can be easily adjusted by changing the value of passive components. The feedback limitation of the circuit is discussed. With the maximum possible transimpedance of 5.3 MΩ when using an 0402 surface mount resistor, the preamplifier was estimated to be able to detect ∼110 charges in a single scan. PMID:22225232

Sensation Seeking as a Moderator of Gain- and Loss-Framed HIV-Test Promotion Message Effects.

PubMed

Hull, Shawnika J; Hong, Yangsun

2016-01-01

This study used an experiment (N = 504) to test whether the fit between sensation-seeking disposition and frame enhances the persuasiveness of gain- and loss-framed HIV test promotion messages. Gain- and loss-framed messages may be consistent with low and high sensation seekers' disposition with respect to risk behavior. We hypothesized that a loss-framed message would be more persuasive for high sensation seekers and that a gain-framed message should be more effective for low sensation seekers. We also expected elaboration to mediate the interaction. Results demonstrated the hypothesized interaction. When the message frame fit with the viewer's way of thinking, the persuasive power of the message was enhanced. The mediation hypothesis was not supported. Practical implications for targeting and message design are discussed.

Loss/gain-induced ultrathin antireflection coatings

PubMed Central

Luo, Jie; Li, Sucheng; Hou, Bo; Lai, Yun

2016-01-01

Tradional antireflection coatings composed of dielectric layers usually require the thickness to be larger than quarter wavelength. Here, we demonstrate that materials with permittivity or permeability dominated by imaginary parts, i.e. lossy or gain media, can realize non-resonant antireflection coatings in deep sub-wavelength scale. Interestingly, while the reflected waves are eliminated as in traditional dielectric antireflection coatings, the transmitted waves can be enhanced or reduced, depending on whether gain or lossy media are applied, respectively. We provide a unified theory for the design of such ultrathin antireflection coatings, showing that under different polarizations and incident angles, different types of ultrathin coatings should be applied. Especially, under transverse magnetic polarization, the requirement shows a switch between gain and lossy media at Brewster angle. As a proof of principle, by using conductive films as a special type of lossy antireflection coatings, we experimentally demonstrate the suppression of Fabry-Pérot resonances in a broad frequency range for microwaves. This valuable functionality can be applied to remove undesired resonant effects, such as the frequency-dependent side lobes induced by resonances in dielectric coverings of antennas. Our work provides a guide for the design of ultrathin antireflection coatings as well as their applications in broadband reflectionless devices. PMID:27349750

Characterization of phospholipase C gamma enzymes with gain-of-function mutations.

PubMed

Everett, Katy L; Bunney, Tom D; Yoon, Youngdae; Rodrigues-Lima, Fernando; Harris, Richard; Driscoll, Paul C; Abe, Koichiro; Fuchs, Helmut; de Angelis, Martin Hrabé; Yu, Philipp; Cho, Wohnwa; Katan, Matilda

2009-08-21

Phospholipase C gamma isozymes (PLC gamma 1 and PLC gamma 2) have a crucial role in the regulation of a variety of cellular functions. Both enzymes have also been implicated in signaling events underlying aberrant cellular responses. Using N-ethyl-N-nitrosourea (ENU) mutagenesis, we have recently identified single point mutations in murine PLC gamma 2 that lead to spontaneous inflammation and autoimmunity. Here we describe further, mechanistic characterization of two gain-of-function mutations, D993G and Y495C, designated as ALI5 and ALI14. The residue Asp-993, mutated in ALI5, is a conserved residue in the catalytic domain of PLC enzymes. Analysis of PLC gamma 1 and PLC gamma 2 with point mutations of this residue showed that removal of the negative charge enhanced PLC activity in response to EGF stimulation or activation by Rac. Measurements of PLC activity in vitro and analysis of membrane binding have suggested that ALI5-type mutations facilitate membrane interactions without compromising substrate binding and hydrolysis. The residue mutated in ALI14 (Tyr-495) is within the spPH domain. Replacement of this residue had no effect on folding of the domain and enhanced Rac activation of PLC gamma 2 without increasing Rac binding. Importantly, the activation of the ALI14-PLC gamma 2 and corresponding PLC gamma 1 variants was enhanced in response to EGF stimulation and bypassed the requirement for phosphorylation of critical tyrosine residues. ALI5- and ALI14-type mutations affected basal activity only slightly; however, their combination resulted in a constitutively active PLC. Based on these data, we suggest that each mutation could compromise auto-inhibition in the inactive PLC, facilitating the activation process; in addition, ALI5-type mutations could enhance membrane interaction in the activated state.

Gain and refractive index dynamics in p-doped InAs quantum dash semiconductor optical amplifiers

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

Komolibus, Katarzyna; Tyndall National Institute, University College Cork, Cork T12 R5CP; Piwonski, Tomasz, E-mail: tomasz.piwonski@tyndall.ie

The ultrafast carrier dynamics in a p-doped dash-in-a-well structure at 1.5 μm is experimentally investigated. An analysis of the timescales related to carrier relaxation and escape processes as well as the “dynamical” linewidth enhancement factor is presented and compared with results obtained from similar un-doped materials. Intentional p-doping of the active region results in an enhancement of the intermediate timescale of the gain dynamics associated with phonon-assisted electron capture and a reduction of the α-factor due to increased differential gain.

Regulation of the neuropathy-associated Pmp22 gene by a distal super-enhancer.

PubMed

Pantera, Harrison; Moran, John J; Hung, Holly A; Pak, Evgenia; Dutra, Amalia; Svaren, John

2018-05-16

Peripheral nerve myelination is adversely affected in the most common form of the hereditary peripheral neuropathy called Charcot-Marie-Tooth Disease. This form, classified as CMT1A, is caused by a 1.4 Mb duplication on chromosome 17, which includes the abundantly expressed Schwann cell myelin gene, Peripheral Myelin Protein 22 (PMP22). This is one of the most common copy number variants causing neurological disease. Overexpression of Pmp22 in rodent models recapitulates several aspects of neuropathy, and reduction of Pmp22 in such models results in amelioration of the neuropathy phenotype. Recently we identified a potential super-enhancer approximately 90-130 kb upstream of the Pmp22 transcription start sites. This super-enhancer encompasses a cluster of individual enhancers that have the acetylated histone H3K27 active enhancer mark, and coincides with smaller duplications identified in patients with milder CMT1A-like symptoms, where the PMP22 coding region itself was not part of the duplication. In this study, we have utilized genome editing to create a deletion of this super-enhancer to determine its role in Pmp22 regulation. Our data show a significant decrease in Pmp22 transcript expression using allele-specific internal controls. Moreover, the P2 promoter of the Pmp22 gene, which is used in other cell types, is affected, but we find that the Schwann cell-specific P1 promoter is disproportionately more sensitive to loss of the super-enhancer. These data show for the first time the requirement of these upstream enhancers for full Pmp22 expression.

Cell-specific gain modulation by synaptically released zinc in cortical circuits of audition.

PubMed

Anderson, Charles T; Kumar, Manoj; Xiong, Shanshan; Tzounopoulos, Thanos

2017-09-09

In many excitatory synapses, mobile zinc is found within glutamatergic vesicles and is coreleased with glutamate. Ex vivo studies established that synaptically released (synaptic) zinc inhibits excitatory neurotransmission at lower frequencies of synaptic activity but enhances steady state synaptic responses during higher frequencies of activity. However, it remains unknown how synaptic zinc affects neuronal processing in vivo. Here, we imaged the sound-evoked neuronal activity of the primary auditory cortex in awake mice. We discovered that synaptic zinc enhanced the gain of sound-evoked responses in CaMKII-expressing principal neurons, but it reduced the gain of parvalbumin- and somatostatin-expressing interneurons. This modulation was sound intensity-dependent and, in part, NMDA receptor-independent. By establishing a previously unknown link between synaptic zinc and gain control of auditory cortical processing, our findings advance understanding about cortical synaptic mechanisms and create a new framework for approaching and interpreting the role of the auditory cortex in sound processing.

Functional assessment of human enhancer activities using whole-genome STARR-sequencing.

PubMed

Liu, Yuwen; Yu, Shan; Dhiman, Vineet K; Brunetti, Tonya; Eckart, Heather; White, Kevin P

2017-11-20

Genome-wide quantification of enhancer activity in the human genome has proven to be a challenging problem. Recent efforts have led to the development of powerful tools for enhancer quantification. However, because of genome size and complexity, these tools have yet to be applied to the whole human genome.  In the current study, we use a human prostate cancer cell line, LNCaP as a model to perform whole human genome STARR-seq (WHG-STARR-seq) to reliably obtain an assessment of enhancer activity. This approach builds upon previously developed STARR-seq in the fly genome and CapSTARR-seq techniques in targeted human genomic regions. With an improved library preparation strategy, our approach greatly increases the library complexity per unit of starting material, which makes it feasible and cost-effective to explore the landscape of regulatory activity in the much larger human genome. In addition to our ability to identify active, accessible enhancers located in open chromatin regions, we can also detect sequences with the potential for enhancer activity that are located in inaccessible, closed chromatin regions. When treated with the histone deacetylase inhibitor, Trichostatin A, genes nearby this latter class of enhancers are up-regulated, demonstrating the potential for endogenous functionality of these regulatory elements. WHG-STARR-seq provides an improved approach to current pipelines for analysis of high complexity genomes to gain a better understanding of the intricacies of transcriptional regulation.

E2 Ubiquitin-conjugating Enzyme, UBE2C Gene, Is Reciprocally Regulated by Wild-type and Gain-of-Function Mutant p53.

PubMed

Bajaj, Swati; Alam, Sk Kayum; Roy, Kumar Singha; Datta, Arindam; Nath, Somsubhra; Roychoudhury, Susanta

2016-07-01

Spindle assembly checkpoint governs proper chromosomal segregation during mitosis to ensure genomic stability. At the cellular level, this event is tightly regulated by UBE2C, an E2 ubiquitin-conjugating enzyme that donates ubiquitin to the anaphase-promoting complex/cyclosome. This, in turn, facilitates anaphase-onset by ubiquitin-mediated degradation of mitotic substrates. UBE2C is an important marker of chromosomal instability and has been associated with malignant growth. However, the mechanism of its regulation is largely unexplored. In this study, we report that UBE2C is transcriptionally activated by the gain-of-function (GOF) mutant p53, although it is transcriptionally repressed by wild-type p53. We showed that wild-type p53-mediated inhibition of UBE2C is p21-E2F4-dependent and GOF mutant p53-mediated transactivation of UBE2C is NF-Y-dependent. We further explored that DNA damage-induced wild-type p53 leads to spindle assembly checkpoint arrest by repressing UBE2C, whereas mutant p53 causes premature anaphase exit by increasing UBE2C expression in the presence of 5-fluorouracil. Identification of UBE2C as a target of wild-type and GOF mutant p53 further highlights the contribution of p53 in regulation of spindle assembly checkpoint. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Improvements in Cardiovascular Risk Factors in Young Adults in a Randomized Trial of Approaches to Weight Gain Prevention

PubMed Central

Wing, Rena R.; Tate, Deborah F.; Garcia, Katelyn R.; Bahnson, Judy; Lewis, Cora E.; Espeland, Mark A.

2017-01-01

Objective Weight gain occurs commonly in young adults and increases cardiovascular (CVD) risk. We previously reported that two self-regulation interventions reduced weight gain relative to control. Here we examine whether these interventions also benefit CVD risk factors. Methods SNAP (Study of Novel Approaches to Weight Gain Prevention) was a randomized trial in 2 academic settings (N=599; 18–35 years; body mass index 21–30 kg/m2) comparing two interventions (Self-Regulation with Small Changes; Self-Regulation with Large Changes) and Control. Small Changes taught participants to make daily small changes (approximately 100 calorie) in intake and activity. Large Changes taught participants to initially lose 5–10 pounds to buffer anticipated weight gains. CVD risk factors were assessed at baseline and 2 years in 471 participants. Results Although Large Changes was associated with more beneficial changes in glucose, insulin, and HOMA-IR than Control, these differences were not significant after adjusting for multiple comparisons or 2-year weight change. Comparison of participants grouped by percent weight change baseline to 2 years showed significant differences for several CVD risk factors, with no interaction with treatment condition. Conclusions Magnitude of weight change, rather than specific weight gain prevention interventions, was related to changes in CVD risk factors in young adults. PMID:28782918

Stimulated Raman spectroscopy and nanoscopy of molecules using near field photon induced forces without resonant electronic enhancement gain

NASA Astrophysics Data System (ADS)

Tamma, Venkata Ananth; Huang, Fei; Nowak, Derek; Kumar Wickramasinghe, H.

2016-06-01

We report on stimulated Raman spectroscopy and nanoscopy of molecules, excited without resonant electronic enhancement gain, and recorded using near field photon induced forces. Photon-induced interaction forces between the sharp metal coated silicon tip of an Atomic Force Microscope (AFM) and a sample resulting from stimulated Raman excitation were detected. We controlled the tip to sample spacing using the higher order flexural eigenmodes of the AFM cantilever, enabling the tip to come very close to the sample. As a result, the detection sensitivity was increased compared with previous work on Raman force microscopy. Raman vibrational spectra of azobenzene thiol and l-phenylalanine were measured and found to agree well with published results. Near-field force detection eliminates the need for far-field optical spectrometer detection. Recorded images show spatial resolution far below the optical diffraction limit. Further optimization and use of ultrafast pulsed lasers could push the detection sensitivity towards the single molecule limit.

Stimulated Raman spectroscopy and nanoscopy of molecules using near field photon induced forces without resonant electronic enhancement gain

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

Tamma, Venkata Ananth; Huang, Fei; Kumar Wickramasinghe, H., E-mail: hkwick@uci.edu

We report on stimulated Raman spectroscopy and nanoscopy of molecules, excited without resonant electronic enhancement gain, and recorded using near field photon induced forces. Photon-induced interaction forces between the sharp metal coated silicon tip of an Atomic Force Microscope (AFM) and a sample resulting from stimulated Raman excitation were detected. We controlled the tip to sample spacing using the higher order flexural eigenmodes of the AFM cantilever, enabling the tip to come very close to the sample. As a result, the detection sensitivity was increased compared with previous work on Raman force microscopy. Raman vibrational spectra of azobenzene thiol andmore » l-phenylalanine were measured and found to agree well with published results. Near-field force detection eliminates the need for far-field optical spectrometer detection. Recorded images show spatial resolution far below the optical diffraction limit. Further optimization and use of ultrafast pulsed lasers could push the detection sensitivity towards the single molecule limit.« less

Application of variable-gain output feedback for high-alpha control

NASA Technical Reports Server (NTRS)

Ostroff, Aaron J.

1990-01-01

A variable-gain, optimal, discrete, output feedback design approach that is applied to a nonlinear flight regime is described. The flight regime covers a wide angle-of-attack range that includes stall and post stall. The paper includes brief descriptions of the variable-gain formulation, the discrete-control structure and flight equations used to apply the design approach, and the high performance airplane model used in the application. Both linear and nonlinear analysis are shown for a longitudinal four-model design case with angles of attack of 5, 15, 35, and 60 deg. Linear and nonlinear simulations are compared for a single-point longitudinal design at 60 deg angle of attack. Nonlinear simulations for the four-model, multi-mode, variable-gain design include a longitudinal pitch-up and pitch-down maneuver and high angle-of-attack regulation during a lateral maneuver.

Aroma enhancement and enzymolysis regulation of grape wine using β-glycosidase

PubMed Central

Zhu, Feng-Mei; Du, Bin; Li, Jun

2014-01-01

Adding β-glycosidase into grape wine for enhancing aroma was investigated using gas chromatography-mass spectrometry (GC-MS) and Kramer sensory evaluation. Compared with the extract from control wines, the extract from enzyme-treated wines increased more aromatic compounds using steam distillation extraction (SDE) and GC-MS analyses. Theses aromatic compounds were as follows: 3-methyl-1-butanol formate, 3-pentanol, furfural, 3-methyl-butanoic acid, 2-methyl-butanoic acid, 3-hydroxy-butanoic acid ethyl ester, hexanoic acid, hexanoic acid ethyl ester, benzyl alcohol, octanoic acid, octanoic acid ethyl ester, dodecanoic acid, and ethyl ester. The enzymolysis regulation conditions, including enzymolysis temperature, enzymolysis time, and enzyme amount, were optimized through L9(34) orthogonal test. Kramer sensory evaluation was performed by an 11-man panel of judges. The optimum enzymolysis regulation conditions were found to be temperature of 45°C, enzymolysis time of 90 min, and enzyme amount of 58.32 U/mL grape wine, respectively. The Kramer sensory evaluation supported that the enzyme-treated wines produced a stronger fragrance. PMID:24804072

The LIM protein complex establishes a retinal circuitry of visual adaptation by regulating Pax6 α-enhancer activity

PubMed Central

Kim, Yeha; Lim, Soyeon; Ha, Taejeong; Song, You-Hyang; Sohn, Young-In; Park, Dae-Jin; Paik, Sun-Sook; Kim-Kaneyama, Joo-ri; Song, Mi-Ryoung; Leung, Amanda; Levine, Edward M; Kim, In-Beom; Goo, Yong Sook; Lee, Seung-Hee; Kang, Kyung Hwa; Kim, Jin Woo

2017-01-01

The visual responses of vertebrates are sensitive to the overall composition of retinal interneurons including amacrine cells, which tune the activity of the retinal circuitry. The expression of Paired-homeobox 6 (PAX6) is regulated by multiple cis-DNA elements including the intronic α-enhancer, which is active in GABAergic amacrine cell subsets. Here, we report that the transforming growth factor ß1-induced transcript 1 protein (Tgfb1i1) interacts with the LIM domain transcription factors Lhx3 and Isl1 to inhibit the α-enhancer in the post-natal mouse retina. Tgfb1i1-/- mice show elevated α-enhancer activity leading to overproduction of Pax6ΔPD isoform that supports the GABAergic amacrine cell fate maintenance. Consequently, the Tgfb1i1-/- mouse retinas show a sustained light response, which becomes more transient in mice with the auto-stimulation-defective Pax6ΔPBS/ΔPBS mutation. Together, we show the antagonistic regulation of the α-enhancer activity by Pax6 and the LIM protein complex is necessary for the establishment of an inner retinal circuitry, which controls visual adaptation. DOI: http://dx.doi.org/10.7554/eLife.21303.001 PMID:28139974

Adaptor proteins GIR1 and GIR2. I. Interaction with the repressor GLABRA2 and regulation of root hair development.

PubMed

Wu, Renhong; Citovsky, Vitaly

2017-07-01

Plants use specialized root outgrowths, termed root hairs, to enhance acquisition of nutrients and water, help secure anchorage, and facilitate interactions with soil microbiome. One of the major regulators of this process is GLABRA2 (GL2), a transcriptional repressor of root hair differentiation. However, regulation of the GL2-function is relatively well characterized, it remains completely unknown whether GL2 itself functions in complex with other transcriptional regulators. We identified GIR1 and GIR2, a plant-specific two-member family of closely related proteins that interact with GL2. Loss-of-function mutants of GIR1 and GIR2 enhanced development of root hair whereas gain-of-function mutants repressed it. Thus, GIR1 and GIR2 might function as adaptor proteins that associate with GL2 and participate in control of root hair formation. Copyright © 2017 Elsevier Inc. All rights reserved.

Graphene quantum dots as enhanced plant growth regulators: effects on coriander and garlic plants.

PubMed

Chakravarty, Disha; Erande, Manisha B; Late, Dattatray J

2015-10-01

We report investigations on the use of graphene quantum dots for growth enhancement in coriander (Coriandrum sativam L.) and garlic (Allium sativum) plants. The as-received seeds of coriander and garlic were treated with 0.2 mg mL(-1) of graphene quantum dots for 3 h before planting. Graphene quantum dots enhanced the growth rate in coriander and garlic plants, including leaves, roots, shoots, flowers and fruits, when the seeds were treated with graphene quantum dots. Our investigations open up the opportunity to use graphene quantum dots as plant growth regulators that can be used in a variety of other food plants for high yield. © 2015 Society of Chemical Industry.

Child Gain Approach and Loss Avoidance Behavior: Relationships With Depression Risk, Negative Mood, and Anhedonia.

PubMed

Luking, Katherine R; Pagliaccio, David; Luby, Joan L; Barch, Deanna M

2015-08-01

Reduced reward responsiveness and altered response to loss of reward are observed in adults with major depressive disorder (MDD) and adolescents at increased risk for MDD based on family history. However, it is unclear whether altered behavioral responsiveness to reward/loss is a lifelong marker of MDD risk, which is evident before the normative adolescent increase in incentive responding. Healthy 7- to 10-year-old children of mothers with MDD (high risk: n = 27) or without MDD (low risk: n = 42) performed 2 signal detection tasks assessing response bias toward reward (approach) and away from loss (avoidance). Differences in approach/avoidance were related to MDD risk, child general depressive symptoms (maternal report), child-reported anhedonic symptoms, and child-reported negative mood symptoms via repeated-measures analysis of variance. MDD risk did not significantly relate to gain approach or loss avoidance. However, within high-risk children, higher numbers of maternal depressive episodes predicted blunted loss avoidance. Blunted gain approach was related to elevated anhedonic symptoms, whereas enhanced loss avoidance was related to elevated negative mood. Elevated negative mood was further related to blunted gain approach in high-risk children but related to enhanced gain approach in low-risk children. In children, individual differences in specific depressive symptoms and recurrence of maternal depression significantly predicted gain approach/loss avoidance, but the presence/absence of maternal MDD did not. Child depressive symptoms characterized by low positive affect (anhedonia) were related to blunted gain responsiveness, whereas elevated depressed/negative mood was related to enhanced loss responsiveness. Findings suggest that relations between gain approach and negative mood may be an important distinction between those at high versus low risk for MDD. Copyright © 2015 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc

Role of Dlx6 in regulation of an endothelin-1-dependent, dHAND branchial arch enhancer

PubMed Central

Charité, Jeroen; McFadden, David G.; Merlo, Giorgio; Levi, Giovanni; Clouthier, David E.; Yanagisawa, Masashi; Richardson, James A.; Olson, Eric N.

2001-01-01

Neural crest cells play a key role in craniofacial development. The endothelin family of secreted polypeptides regulates development of several neural crest sublineages, including the branchial arch neural crest. The basic helix–loop–helix transcription factor dHAND is also required for craniofacial development, and in endothelin-1 (ET-1) mutant embryos, dHAND expression in the branchial arches is down-regulated, implicating it as a transcriptional effector of ET-1 action. To determine the mechanism that links ET-1 signaling to dHAND transcription, we analyzed the dHAND gene for cis-regulatory elements that control transcription in the branchial arches. We describe an evolutionarily conserved dHAND enhancer that requires ET-1 signaling for activity. This enhancer contains four homeodomain binding sites that are required for branchial arch expression. By comparing protein binding to these sites in branchial arch extracts from endothelin receptor A (EdnrA) mutant and wild-type mouse embryos, we identified Dlx6, a member of the Distal-less family of homeodomain proteins, as an ET-1-dependent binding factor. Consistent with this conclusion, Dlx6 was down-regulated in branchial arches from EdnrA mutant mice. These results suggest that Dlx6 acts as an intermediary between ET-1 signaling and dHAND transcription during craniofacial morphogenesis. PMID:11711438

Altered reward anticipation: Potential explanation for weight gain in schizophrenia?

PubMed

Grimm, Oliver; Kaiser, Stefan; Plichta, Michael M; Tobler, Philippe N

2017-04-01

Obesity and weight gain are severe complications of mental illness, especially schizophrenia. They result from changes in lifestyle and nutrition, side effects of medication and other, less well-understood factors. Recent studies suggest that obesity and weight gain are linked to psychopathology. Specifically, severe psychopathology is associated with greater weight dysregulation, typically weight gain. However, our knowledge about the neuroscientific basis of weight gain in schizophrenia is currently limited. We propose that altered reward anticipation, which in turn is related to striatal dopaminergic dysregulation, may explain why obesity is more prevalent in individuals with mental illness. We review evidence that reward anticipation and weight change are linked by a core deficit in dopaminergic striatal circuits. Several lines of evidence, running from animal studies to preclinical and clinical studies, suggest that striatal dopaminergic neurotransmission is a major hub for the regulation of eating behavior and that dopamine links eating behavior to other motivated behavior. From this perspective, the present review outlines a unifying perspective on dopaminergic reward anticipation as a theoretical frame to link weight gain, medication effects and psychopathology. We derive important but open empirical questions and present perspectives for new therapeutic concepts. Copyright © 2017 Elsevier Ltd. All rights reserved.

Regulation of Bacteria-Induced Intercellular Adhesion Molecule-1 by CCAAT/Enhancer Binding Proteins

PubMed Central

Manzel, Lori J.; Chin, Cecilia L.; Behlke, Mark A.; Look, Dwight C.

2009-01-01

Direct interaction between bacteria and epithelial cells may initiate or amplify the airway response through induction of epithelial defense gene expression by nuclear factor-κB (NF-κB). However, multiple signaling pathways modify NF-κB effects to modulate gene expression. In this study, the effects of CCAAT/enhancer binding protein (C/EBP) family members on induction of the leukocyte adhesion glycoprotein intercellular adhesion molecule-1 (ICAM-1) was examined in primary cultures of human tracheobronchial epithelial cells incubated with nontypeable Haemophilus influenzae. Increased ICAM-1 gene transcription in response to H. influenzae required gene sequences located at −200 to −135 in the 5′-flanking region that contain a C/EBP-binding sequence immediately upstream of the NF-κB enhancer site. Constitutive C/EBPβ was found to have an important role in epithelial cell ICAM-1 regulation, while the adjacent NF-κB sequence binds the RelA/p65 and NF-κB1/p50 members of the NF-κB family to induce ICAM-1 expression in response to H. influenzae. The expression of C/EBP proteins is not regulated by p38 mitogen-activated protein kinase activation, but p38 affects gene transcription by increasing the binding of TATA-binding protein to TATA-box–containing gene sequences. Epithelial cell ICAM-1 expression in response to H. influenzae was decreased by expressing dominant-negative protein or RNA interference against C/EBPβ, confirming its role in ICAM-1 regulation. Although airway epithelial cells express multiple constitutive and inducible C/EBP family members that bind C/EBP sequences, the results indicate that C/EBPβ plays a central role in modulation of NF-κB–dependent defense gene expression in human airway epithelial cells after exposure to H. influenzae. PMID:18703796

Environmental health and nursing: piloting a technology-enhanced distance learning module.

PubMed

Olson, Debra; Stedman-Smith, Maggie; Fredrickson, Ann

2005-08-01

The results of a pilot study evaluating a technology-enhanced distance learning module to impart environmental health core concepts to nurses are presented in this article. The internet-based module was developed for continuing professional education and imparts principles of adult education through interactive features including simulated clinical vignettes, an environmental justice case study, and hyperlinks to websites related to environmental protection and health regulation. Mean gains between pre- and post-tests; participant identification of adult learning principles as advanced by Knowles, Holton, and Swanson (1998); and satisfaction were measured among participating RNs (N = 34). A 6% mean gain in learning occurred between pre- and post-tests (95% CI .51 to 1.37, p < .0001). No significant differences in learning occurred for those who prefer face-to-face instruction and those who tend to procrastinate. Ninety-four percent of respondents indicated they were satisfied or very satisfied with the module. A strong association was found between recognition of adult learning principles as enhancing the assimilation of knowledge and competencies of environmental health and high satisfaction with the module. Distance learning via the Internet shows promise as a format to promote environmental health education for nurses.

Age differences in gain- and loss-motivated attention.

PubMed

Williams, Ryan S; Biel, Anna Lena; Dyson, Benjamin J; Spaniol, Julia

2017-02-01

Adaptive gain theory (Aston-Jones & Cohen, 2005) suggests that the phasic release of norepinephrine (NE) to cortical areas reflects changes in the utility of ongoing tasks. In the context of aging, this theory raises interesting questions, given that the motivations of older adults differ from those of younger adults. According to socioemotional selectivity theory (Carstensen, Isaacowitz, & Charles, 1999), aging is associated with greater emphasis on emotion-regulation goals, leading older adults to prioritize positive over negative information. This suggests that the phasic release of NE in response to threatening stimuli may be diminished in older adults. In the present study, younger adults (aged 18-34years) and older adults (60-82years) completed the Attention Network Test (ANT), modified to include an incentive manipulation. A behavioral index of attentional alerting served as a marker of phasic arousal. For younger adults, this marker correlated with the effect of both gain and loss incentives on performance. For older adults, in contrast, the correlation between phasic arousal and incentive sensitivity held for gain incentives only. These findings suggest that the enlistment of phasic NE activity may be specific to approach-oriented motivation in older adults. Copyright © 2016. Published by Elsevier Inc.

DHEA Enhances Emotion Regulation Neurocircuits and Modulates Memory for Emotional Stimuli

PubMed Central

Sripada, Rebecca K; Marx, Christine E; King, Anthony P; Rajaram, Nirmala; Garfinkel, Sarah N; Abelson, James L; Liberzon, Israel

2013-01-01

Dehydroepiandrosterone (DHEA) is a neurosteroid with anxiolytic, antidepressant, and antiglucocorticoid properties. It is endogenously released in response to stress, and may reduce negative affect when administered exogenously. Although there have been multiple reports of DHEA's antidepressant and anxiolytic effects, no research to date has examined the neural pathways involved. In particular, brain imaging has not been used to link neurosteroid effects to emotion neurocircuitry. To investigate the brain basis of DHEA's impact on emotion modulation, patients were administered 400 mg of DHEA (N=14) or placebo (N=15) and underwent 3T fMRI while performing the shifted-attention emotion appraisal task (SEAT), a test of emotional processing and regulation. Compared with placebo, DHEA reduced activity in the amygdala and hippocampus, enhanced connectivity between the amygdala and hippocampus, and enhanced activity in the rACC. These activation changes were associated with reduced negative affect. DHEA reduced memory accuracy for emotional stimuli, and also reduced activity in regions associated with conjunctive memory encoding. These results demonstrate that DHEA reduces activity in regions associated with generation of negative emotion and enhances activity in regions linked to regulatory processes. Considering that activity in these regions is altered in mood and anxiety disorders, our results provide initial neuroimaging evidence that DHEA may be useful as a pharmacological intervention for these conditions and invite further investigation into the brain basis of neurosteroid emotion regulatory effects. PMID:23552182

Changing the Spatial Scope of Attention Alters Patterns of Neural Gain in Human Cortex

PubMed Central

Garcia, Javier O.; Rungratsameetaweemana, Nuttida; Sprague, Thomas C.

2014-01-01

Over the last several decades, spatial attention has been shown to influence the activity of neurons in visual cortex in various ways. These conflicting observations have inspired competing models to account for the influence of attention on perception and behavior. Here, we used electroencephalography (EEG) to assess steady-state visual evoked potentials (SSVEP) in human subjects and showed that highly focused spatial attention primarily enhanced neural responses to high-contrast stimuli (response gain), whereas distributed attention primarily enhanced responses to medium-contrast stimuli (contrast gain). Together, these data suggest that different patterns of neural modulation do not reflect fundamentally different neural mechanisms, but instead reflect changes in the spatial extent of attention. PMID:24381272

Emotion Regulation through Movement: Unique Sets of Movement Characteristics are Associated with and Enhance Basic Emotions.

PubMed

Shafir, Tal; Tsachor, Rachelle P; Welch, Kathleen B

2015-01-01

We have recently demonstrated that motor execution, observation, and imagery of movements expressing certain emotions can enhance corresponding affective states and therefore could be used for emotion regulation. But which specific movement(s) should one use in order to enhance each emotion? This study aimed to identify, using Laban Movement Analysis (LMA), the Laban motor elements (motor characteristics) that characterize movements whose execution enhances each of the basic emotions: anger, fear, happiness, and sadness. LMA provides a system of symbols describing its motor elements, which gives a written instruction (motif) for the execution of a movement or movement-sequence over time. Six senior LMA experts analyzed a validated set of video clips showing whole body dynamic expressions of anger, fear, happiness and sadness, and identified the motor elements that were common to (appeared in) all clips expressing the same emotion. For each emotion, we created motifs of different combinations of the motor elements common to all clips of the same emotion. Eighty subjects from around the world read and moved those motifs, to identify the emotion evoked when moving each motif and to rate the intensity of the evoked emotion. All subjects together moved and rated 1241 motifs, which were produced from 29 different motor elements. Using logistic regression, we found a set of motor elements associated with each emotion which, when moved, predicted the feeling of that emotion. Each emotion was predicted by a unique set of motor elements and each motor element predicted only one emotion. Knowledge of which specific motor elements enhance specific emotions can enable emotional self-regulation through adding some desired motor qualities to one's personal everyday movements (rather than mimicking others' specific movements) and through decreasing motor behaviors which include elements that enhance negative emotions.

Emotion Regulation through Movement: Unique Sets of Movement Characteristics are Associated with and Enhance Basic Emotions

PubMed Central

Shafir, Tal; Tsachor, Rachelle P.; Welch, Kathleen B.

2016-01-01

We have recently demonstrated that motor execution, observation, and imagery of movements expressing certain emotions can enhance corresponding affective states and therefore could be used for emotion regulation. But which specific movement(s) should one use in order to enhance each emotion? This study aimed to identify, using Laban Movement Analysis (LMA), the Laban motor elements (motor characteristics) that characterize movements whose execution enhances each of the basic emotions: anger, fear, happiness, and sadness. LMA provides a system of symbols describing its motor elements, which gives a written instruction (motif) for the execution of a movement or movement-sequence over time. Six senior LMA experts analyzed a validated set of video clips showing whole body dynamic expressions of anger, fear, happiness and sadness, and identified the motor elements that were common to (appeared in) all clips expressing the same emotion. For each emotion, we created motifs of different combinations of the motor elements common to all clips of the same emotion. Eighty subjects from around the world read and moved those motifs, to identify the emotion evoked when moving each motif and to rate the intensity of the evoked emotion. All subjects together moved and rated 1241 motifs, which were produced from 29 different motor elements. Using logistic regression, we found a set of motor elements associated with each emotion which, when moved, predicted the feeling of that emotion. Each emotion was predicted by a unique set of motor elements and each motor element predicted only one emotion. Knowledge of which specific motor elements enhance specific emotions can enable emotional self-regulation through adding some desired motor qualities to one's personal everyday movements (rather than mimicking others' specific movements) and through decreasing motor behaviors which include elements that enhance negative emotions. PMID:26793147

Enhancing Neuroplasticity to Augment Cognitive Remediation in Schizophrenia.

PubMed

Jahshan, Carol; Rassovsky, Yuri; Green, Michael F

2017-01-01

There is a burgeoning need for innovative treatment strategies to improve the cognitive deficits in schizophrenia. Cognitive remediation (CR) is effective at the group level, but the variability in treatment response is large. Given that CR may depend on intact neuroplasticity to produce cognitive gains, it is reasonable to combine it with strategies that harness patients' neuroplastic potential. In this review, we discuss two non-pharmacological approaches that can enhance neuroplasticity and possibly augment the effects of CR in schizophrenia: physical exercise and transcranial direct current stimulation (tDCS). Substantial body of evidence supports the beneficial effect of physical exercise on cognition, and a handful of studies in schizophrenia have shown that physical exercise in conjunction with CR has a larger impact on cognition than CR alone. Physical exercise is thought to stimulate neuroplasticity through the regulation of central growth factors, and current evidence points to brain-derived neurotrophic factor as the potential underlying mechanism through which physical exercise might enhance the effectiveness of CR. tDCS has emerged as a potential tool for cognitive enhancement and seems to affect the cellular mechanisms involved in long-term potentiation (LTP). A few reports have demonstrated the feasibility of integrating tDCS with CR in schizophrenia, but there are insufficient data to determine if this multimodal approach leads to incremental performance gain in patients. Larger randomized controlled trials are necessary to understand the mechanisms of the combined tDCS-CR intervention. Future research should take advantage of new developments in neuroplasticity paradigms to examine the effects of these interventions on LTP.

Gain control by layer six in cortical circuits of vision.

PubMed

Olsen, Shawn R; Bortone, Dante S; Adesnik, Hillel; Scanziani, Massimo

2012-02-22

After entering the cerebral cortex, sensory information spreads through six different horizontal neuronal layers that are interconnected by vertical axonal projections. It is believed that through these projections layers can influence each other's response to sensory stimuli, but the specific role that each layer has in cortical processing is still poorly understood. Here we show that layer six in the primary visual cortex of the mouse has a crucial role in controlling the gain of visually evoked activity in neurons of the upper layers without changing their tuning to orientation. This gain modulation results from the coordinated action of layer six intracortical projections to superficial layers and deep projections to the thalamus, with a substantial role of the intracortical circuit. This study establishes layer six as a major mediator of cortical gain modulation and suggests that it could be a node through which convergent inputs from several brain areas can regulate the earliest steps of cortical visual processing.

High-cut characteristics of the baroreflex neural arc preserve baroreflex gain against pulsatile pressure.

PubMed

Kawada, Toru; Zheng, Can; Yanagiya, Yusuke; Uemura, Kazunori; Miyamoto, Tadayoshi; Inagaki, Masashi; Shishido, Toshiaki; Sugimachi, Masaru; Sunagawa, Kenji

2002-03-01

A transfer function from baroreceptor pressure input to sympathetic nerve activity (SNA) shows derivative characteristics in the frequency range below 0.8 Hz in rabbits. These derivative characteristics contribute to a quick and stable arterial pressure (AP) regulation. However, if the derivative characteristics hold up to heart rate frequency, the pulsatile pressure input will yield a markedly augmented SNA signal. Such a signal would saturate the baroreflex signal transduction, thereby disabling the baroreflex regulation of AP. We hypothesized that the transfer gain at heart rate frequency would be much smaller than that predicted from extrapolating the derivative characteristics. In anesthetized rabbits (n = 6), we estimated the neural arc transfer function in the frequency range up to 10 Hz. The transfer gain was lost at a rate of -20 dB/decade when the input frequency exceeded 0.8 Hz. A numerical simulation indicated that the high-cut characteristics above 0.8 Hz were effective to attenuate the pulsatile signal and preserve the open-loop gain when the baroreflex dynamic range was finite.

Fractal Based Triple Band High Gain Monopole Antenna

NASA Astrophysics Data System (ADS)

Pandey, Shashi Kant; Pandey, Ganga Prasad; Sarun, P. M.

2017-10-01

A novel triple-band microstrip fed planar monopole antenna is proposed and investigated. A fractal antenna is created by iterating a narrow pulse (NP) generator model at upper side of modified ground plane, which has a rhombic patch, for enhancing the bandwidth and gain. Three iterations are carried out to study the effects of fractal geometry on the antenna performance. The proposed antenna can operate over three frequency ranges viz, 3.34-4.8 GHz, 5.5-10.6 GHz and 13-14.96 GHz suitable for WLAN 5.2/5.8 GHz, WiMAX 3.5/5.5 GHz and X band applications respectively. Simulated and measured results are in good agreements with each others. Results show that antenna provides wide/ultra wide bandwidths, monopole like radiation patterns and very high antenna gains over the operating frequency bands.

Introductory Biology Students' Use of Enhanced Answer Keys and Reflection Questions to Engage in Metacognition and Enhance Understanding.

PubMed

Sabel, Jaime L; Dauer, Joseph T; Forbes, Cory T

2017-01-01

Providing feedback to students as they learn to integrate individual concepts into complex systems is an important way to help them to develop robust understanding, but it is challenging in large, undergraduate classes for instructors to provide feedback that is frequent and directed enough to help individual students. Various scaffolds can be used to help students engage in self-regulated learning and generate internal feedback to improve their learning. This study examined the use of enhanced answer keys with added reflection questions and instruction as scaffolds for engaging undergraduate students in self-regulated learning within an introductory biology course. Study findings show that both the enhanced answer keys and reflection questions helped students to engage in metacognition and develop greater understanding of biological concepts. Further, students who received additional instruction on the use of the scaffolds changed how they used them and, by the end of the semester, were using the scaffolds in significantly different ways and showed significantly higher learning gains than students who did not receive the instruction. These findings provide evidence for the benefit of designing scaffolds within biology courses that will support students in engaging in metacognition and enhancing their understanding of biological concepts. © 2017 J. L. Sabel et al. CBE—Life Sciences Education © 2017 The American Society for Cell Biology. This article is distributed by The American Society for Cell Biology under license from the author(s). It is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Emotion Regulation Enhancement of Cognitive Behavior Therapy for College Student Problem Drinkers: A Pilot Randomized Controlled Trial

ERIC Educational Resources Information Center

Ford, Julian D.; Grasso, Damion J.; Levine, Joan; Tennen, Howard

2018-01-01

This pilot randomized clinical trial tested an emotion regulation enhancement to cognitive behavior therapy (CBT) with 29 college student problem drinkers with histories of complex trauma and current clinically significant traumatic stress symptoms. Participants received eight face-to-face sessions of manualized Internet-supported CBT for problem…

32 CFR Appendix A to Part 1285 - Gaining Access to DLA Records

Code of Federal Regulations, 2012 CFR

2012-07-01

... Part 1285 National Defense Other Regulations Relating to National Defense DEFENSE LOGISTICS AGENCY MISCELLANEOUS DEFENSE LOGISTICS AGENCY FREEDOM OF INFORMATION ACT PROGRAM Pt. 1285, App. A Appendix A to Part 1285—Gaining Access to DLA Records I. General The Defense Logistics Agency was established pursuant to...

32 CFR Appendix A to Part 1285 - Gaining Access to DLA Records

Code of Federal Regulations, 2011 CFR

2011-07-01

... Part 1285 National Defense Other Regulations Relating to National Defense DEFENSE LOGISTICS AGENCY MISCELLANEOUS DEFENSE LOGISTICS AGENCY FREEDOM OF INFORMATION ACT PROGRAM Pt. 1285, App. A Appendix A to Part 1285—Gaining Access to DLA Records I. General The Defense Logistics Agency was established pursuant to...

32 CFR Appendix A to Part 1285 - Gaining Access to DLA Records

Code of Federal Regulations, 2013 CFR

2013-07-01

... Part 1285 National Defense Other Regulations Relating to National Defense DEFENSE LOGISTICS AGENCY MISCELLANEOUS DEFENSE LOGISTICS AGENCY FREEDOM OF INFORMATION ACT PROGRAM Pt. 1285, App. A Appendix A to Part 1285—Gaining Access to DLA Records I. General The Defense Logistics Agency was established pursuant to...

Implicit emotion regulation affects outcome evaluation

PubMed Central

Yang, Qiwei; Tang, Ping; Luo, Wenbo; Luo, Yue-jia

2015-01-01

Efficient implicit emotion regulation processes, which run without awareness, are important for human well-being. In this study, to investigate the influence of implicit emotion regulation on psychological and electrophysiological responses to gains and losses, participants were required to select between two Chinese four-character idioms to match the meaning of the third one before they performed a monetary gambling task. According to whether their meanings were related to emotion regulation, the idioms fell into two categories. Event-related potentials and self-rating emotional experiences to outcome feedback were recorded during the task. Priming emotion regulation reduced subjective emotional experience to both gains and losses and the amplitudes of the feedback-related negativity, while the P3 component was not influenced. According to these results, we suggest that the application of implicit emotion regulation effectively modulated the subjective emotional experience and the motivational salience of current outcomes without the cost of cognitive resources. This study implicates the potential significance of implicit emotion regulation in decision-making processes. PMID:25332404

Polarization-insensitive optical gain characteristics of highly stacked InAs/GaAs quantum dots

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

Kita, Takashi; Suwa, Masaya; Kaizu, Toshiyuki

2014-06-21

The polarized optical gain characteristics of highly stacked InAs/GaAs quantum dots (QDs) with a thin spacer layer fabricated on an n{sup +}-GaAs (001) substrate were studied in the sub-threshold gain region. Using a 4.0-nm-thick spacer layer, we realized an electronically coupled QD superlattice structure along the stacking direction, which enabled the enhancement of the optical gain of the [001] transverse-magnetic (TM) polarization component. We systematically studied the polarized electroluminescence properties of laser devices containing 30 and 40 stacked InAs/GaAs QDs. The net modal gain was analyzed using the Hakki-Paoli method. Owing to the in-plane shape anisotropy of QDs, the polarizationmore » sensitivity of the gain depends on the waveguide direction. The gain showing polarization isotropy between the TM and transverse-electric polarization components is high for the [110] waveguide structure, which occurs for higher amounts of stacked QDs. Conversely, the isotropy of the [−110] waveguide is easily achieved even if the stacking is relatively low, although the gain is small.« less

High-gain 1.3  μm GaInNAs semiconductor optical amplifier with enhanced temperature stability for all-optical signal processing at 10  Gb/s.

PubMed

Fitsios, D; Giannoulis, G; Korpijärvi, V-M; Viheriälä, J; Laakso, A; Iliadis, N; Dris, S; Spyropoulou, M; Avramopoulos, H; Kanellos, G T; Pleros, N; Guina, M

2015-01-01

We report on the complete experimental evaluation of a GaInNAs/GaAs (dilute nitride) semiconductor optical amplifier that operates at 1.3 μm and exhibits 28 dB gain and a gain recovery time of 100 ps. Successful wavelength conversion operation is demonstrated using pseudorandom bit sequence 2⁷-1 non-return-to-zero bit streams at 5 and 10  Gb/s, yielding error-free performance and showing feasibility for implementation in various signal processing functionalities. The operational credentials of the device are analyzed in various operational regimes, while its nonlinear performance is examined in terms of four-wave mixing. Moreover, characterization results reveal enhanced temperature stability with almost no gain variation around the 1320 nm region for a temperature range from 20°C to 50°C. The operational characteristics of the device, along with the cost and energy benefits of dilute nitride technology, make it very attractive for application in optical access networks and dense photonic integrated circuits.

Fluoxetine potentiates methylphenidate-induced gene regulation in addiction-related brain regions: Concerns for use of cognitive enhancers?

PubMed Central

Steiner, Heinz; Van Waes, Vincent; Marinelli, Michela

2009-01-01

Background There is growing use of psychostimulant cognitive enhancers such as methylphenidate (Ritalin). Methylphenidate differs from the psychostimulant cocaine because it does not enhance brain levels of serotonin. We investigated whether exposure to methylphenidate combined with a serotonin-enhancing medication, the prototypical selective serotonin reuptake inhibitor (SSRI) fluoxetine (Prozac), would produce more “cocaine-like” molecular and behavioral changes. Methods We measured the effects of fluoxetine on gene expression induced by the cognitive enhancer methylphenidate in the striatum and nucleus accumbens of rats, by in situ hybridization histochemistry. We also determined whether fluoxetine modified behavioral effects of methylphenidate. Results Fluoxetine robustly potentiated methylphenidate-induced expression of the transcription factors c-fos and zif 268 throughout the striatum and to some degree in the nucleus accumbens. Fluoxetine also enhanced methylphenidate-induced stereotypical behavior. Conclusions Both potentiated gene regulation in the striatum and the behavioral effects indicate that combining the SSRI fluoxetine with the cognitive enhancer methylphenidate mimics cocaine effects, consistent with an increased risk for substance use disorder. PMID:19931852

LBH Gene Transcription Regulation by the Interplay of an Enhancer Risk Allele and DNA Methylation in Rheumatoid Arthritis.

PubMed

Hammaker, Deepa; Whitaker, John W; Maeshima, Keisuke; Boyle, David L; Ekwall, Anna-Karin H; Wang, Wei; Firestein, Gary S

2016-11-01

To identify nonobvious therapeutic targets for rheumatoid arthritis (RA), we performed an integrative analysis incorporating multiple "omics" data and the Encyclopedia of DNA Elements (ENCODE) database for potential regulatory regions. This analysis identified the limb bud and heart development (LBH) gene, which has risk alleles associated with RA/celiac disease and lupus, and can regulate cell proliferation in RA. We identified a novel LBH transcription enhancer with an RA risk allele (rs906868 G [Ref]/T) 6 kb upstream of the LBH gene with a differentially methylated locus. The confluence of 3 regulatory elements, rs906868, an RA differentially methylated locus, and a putative enhancer, led us to investigate their effects on LBH regulation in fibroblast-like synoviocytes (FLS). We cloned the 1.4-kb putative enhancer with either the rs906868 Ref allele or single-nucleotide polymorphism (SNP) variant into reporter constructs. The constructs were methylated in vitro and transfected into cultured FLS by nucleofection. We found that both variants increased transcription, thereby confirming the region's enhancer function. Unexpectedly, the transcriptional activity of the Ref risk allele was significantly lower than that of the SNP variant and is consistent with low LBH levels as a risk factor for aggressive FLS behavior. Using RA FLS lines with a homozygous Ref or SNP allele, we confirmed that homozygous Ref lines expressed lower LBH messenger RNA levels than did the SNP lines. Methylation significantly reduced enhancer activity for both alleles, indicating that enhancer function is dependent on its methylation status. This study shows how the interplay between genetics and epigenetics can affect expression of LBH in RA. © 2016, American College of Rheumatology.

Giant enhancement of reflectance due to the interplay between surface confined wave modes and nonlinear gain in dielectric media.

PubMed

Kim, Sangbum; Kim, Kihong

2017-12-11

We study theoretically the interplay between the surface confined wave modes and the linear and nonlinear gain of the dielectric layer in the Otto configuration. The surface confined wave modes, such as surface plasmons or waveguide modes, are excited in the dielectric-metal bilayer by obliquely incident p waves. In the purely linear case, we find that the interplay between linear gain and surface confined wave modes can generate a large reflectance peak with its value much greater than 1. As the linear gain parameter increases, the peak appears at smaller incident angles, and the associated modes also change from surface plasmons to waveguide modes. When the nonlinear gain is turned on, the reflectance shows very strong multistability near the incident angles associated with surface confined wave modes. As the nonlinear gain parameter is varied, the reflectance curve undergoes complicated topological changes and sometimes displays separated closed curves. When the nonlinear gain parameter takes an optimally small value, a giant amplification of the reflectance by three orders of magnitude occurs near the incident angle associated with a waveguide mode. We also find that there exists a range of the incident angle where the wave is dissipated rather than amplified even in the presence of gain. We suggest that this can provide the basis for a possible new technology for thermal control in the subwavelength scale.

Comparison of TALE designer transcription factors and the CRISPR/dCas9 in regulation of gene expression by targeting enhancers

PubMed Central

Gao, Xuefei; Tsang, Jason C.H.; Gaba, Fortis; Wu, Donghai; Lu, Liming; Liu, Pentao

2014-01-01

The transcription activator–like effectors (TALEs) and the RNA-guided clustered regularly interspaced short palindromic repeat (CRISPR) associated protein (Cas9) utlilize distinct molecular mechanisms in targeting site recognition. The two proteins can be modified to carry additional functional domains to regulate expression of genomic loci in mammalian cells. In this study, we have compared the two systems in activation and suppression of the Oct4 and Nanog loci by targeting their enhancers. Although both are able to efficiently activate the luciferase reporters, the CRISPR/dCas9 system is much less potent in activating the endogenous loci and in the application of reprogramming somatic cells to iPS cells. Nevertheless, repression by CRISPR/dCas9 is comparable to or even better than TALE repressors. We demonstrated that dCas9 protein binding results in significant physical interference to binding of native transcription factors at enhancer, less efficient active histone markers induction or recruitment of activating complexes in gene activation. This study thus highlighted the merits and drawbacks of transcription regulation by each system. A combined approach of TALEs and CRISPR/dCas9 should provide an optimized solution to regulate genomic loci and to study genetic elements such as enhancers in biological processes including somatic cell reprogramming and guided differentiation. PMID:25223790

DNA breaks and chromatin structural changes enhance the transcription of autoimmune regulator target genes.

PubMed

Guha, Mithu; Saare, Mario; Maslovskaja, Julia; Kisand, Kai; Liiv, Ingrid; Haljasorg, Uku; Tasa, Tõnis; Metspalu, Andres; Milani, Lili; Peterson, Pärt

2017-04-21

The autoimmune regulator (AIRE) protein is the key factor in thymic negative selection of autoreactive T cells by promoting the ectopic expression of tissue-specific genes in the thymic medullary epithelium. Mutations in AIRE cause a monogenic autoimmune disease called autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy. AIRE has been shown to promote DNA breaks via its interaction with topoisomerase 2 (TOP2). In this study, we investigated topoisomerase-induced DNA breaks and chromatin structural alterations in conjunction with AIRE-dependent gene expression. Using RNA sequencing, we found that inhibition of TOP2 religation activity by etoposide in AIRE-expressing cells had a synergistic effect on genes with low expression levels. AIRE-mediated transcription was not only enhanced by TOP2 inhibition but also by the TOP1 inhibitor camptothecin. The transcriptional activation was associated with structural rearrangements in chromatin, notably the accumulation of γH2AX and the exchange of histone H1 with HMGB1 at AIRE target gene promoters. In addition, we found the transcriptional up-regulation to co-occur with the chromatin structural changes within the genomic cluster of carcinoembryonic antigen-like cellular adhesion molecule genes. Overall, our results suggest that the presence of AIRE can trigger molecular events leading to an altered chromatin landscape and the enhanced transcription of low-expressed genes. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

DNA breaks and chromatin structural changes enhance the transcription of autoimmune regulator target genes

PubMed Central

Guha, Mithu; Saare, Mario; Maslovskaja, Julia; Kisand, Kai; Liiv, Ingrid; Haljasorg, Uku; Tasa, Tõnis; Metspalu, Andres; Milani, Lili; Peterson, Pärt

2017-01-01

The autoimmune regulator (AIRE) protein is the key factor in thymic negative selection of autoreactive T cells by promoting the ectopic expression of tissue-specific genes in the thymic medullary epithelium. Mutations in AIRE cause a monogenic autoimmune disease called autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy. AIRE has been shown to promote DNA breaks via its interaction with topoisomerase 2 (TOP2). In this study, we investigated topoisomerase-induced DNA breaks and chromatin structural alterations in conjunction with AIRE-dependent gene expression. Using RNA sequencing, we found that inhibition of TOP2 religation activity by etoposide in AIRE-expressing cells had a synergistic effect on genes with low expression levels. AIRE-mediated transcription was not only enhanced by TOP2 inhibition but also by the TOP1 inhibitor camptothecin. The transcriptional activation was associated with structural rearrangements in chromatin, notably the accumulation of γH2AX and the exchange of histone H1 with HMGB1 at AIRE target gene promoters. In addition, we found the transcriptional up-regulation to co-occur with the chromatin structural changes within the genomic cluster of carcinoembryonic antigen-like cellular adhesion molecule genes. Overall, our results suggest that the presence of AIRE can trigger molecular events leading to an altered chromatin landscape and the enhanced transcription of low-expressed genes. PMID:28242760

The study of breast milk IGF-1, leptin, ghrelin and adiponectin levels as possible reasons of high weight gain in breast-fed infants.

PubMed

Kon, Igor Ya; Shilina, Natalia M; Gmoshinskaya, Maria V; Ivanushkina, Tatiana A

2014-01-01

Excessive consumption of protein that leads to increased blood levels of insulin-like growth factor-1 (IGF-1) is an important risk factor for high growth velocity and obesity in formula-fed infants. However, it is not clear whether these factors can explain the high growth velocity in breast-fed infants. To study the possible links between the growth velocity in breast-fed infants and the levels of protein, IGF-1 and other hormones, which regulate energy homeostasis, in mothers' breast milk. We studied 103 mother-infant pairs. Their daily breast milk intake and level of IGF-1, leptin, ghrelin, adiponectin, protein and fat in breast milk were measured at 1, 2 and 3 months of lactation. The infant group was divided into three subgroups of low, normal and high weight gain tertiles. The breast milk consumed by the infants with high weight gain contained higher levels of IGF-1 than that consumed by those with low weight gain at all periods studied (p = 0.032 at 3 months of lactation), and ghrelin levels were higher at 1 and 2 months and leptin levels at 2 and 3 months of lactation (p < 0.05). A positive correlation was observed between the breast milk IGF-1 level and infant weight gain (r = 0.294, p = 0.043). Total daily breast milk, fat and hormone intake was also higher in the high weight gain group compared to the low weight gain group. One of the reasons for the high growth velocity in breast-fed infants may be the enhanced levels of the studied hormones in breast milk.

Regulation of a mammalian gene bearing a CpG island promoter and a distal enhancer.

PubMed

Berrozpe, Georgina; Bryant, Gene O; Warpinski, Katherine; Ptashne, Mark

2013-08-15

A quantitative nucleosome occupancy assay revealed rules for nucleosome disposition in yeast and showed how disposition affects regulation of the GAL genes. Here, we show how those findings apply to the control of Kit, a mammalian gene. The Kit promoter lies in a CpG island, and its enhancer (active in mast cells) lies some 150 kb upstream. Nucleosomes form with especially high avidities at the Kit promoter, a reaction that, we surmise, ensures extremely low basal expression. In mast cells, transcriptional activators displace nucleosomes that are less tightly formed at the Kit enhancer. In turn, the active enhancer replaces a single Kit promoter nucleosome with the transcriptional machinery, thereby inducing transcription over 1,000-fold. As at the yeast GAL genes, the inhibitory effects of nucleosomes facilitate high factors of induction by mammalian activators working in the absence of specific repressors. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Self-Regulated Learning Strategies of Engineering College Students While Learning Electric Circuit Concepts with Enhanced Guided Notes

ERIC Educational Resources Information Center

Lawanto, Oenardi; Santoso, Harry

2013-01-01

The current study evaluated engineering college students' self-regulated learning (SRL) strategies while learning electric circuit concepts using enhanced guided notes (EGN). Our goal was to describe how students exercise SRL strategies and how their grade performance changes after using EGN. Two research questions guided the study: (1) To what…

Enhancer regions show high histone H3.3 turnover that changes during differentiation

PubMed Central

Deaton, Aimee M; Gómez-Rodríguez, Mariluz; Mieczkowski, Jakub; Tolstorukov, Michael Y; Kundu, Sharmistha; Sadreyev, Ruslan I; Jansen, Lars ET; Kingston, Robert E

2016-01-01

The organization of DNA into chromatin is dynamic; nucleosomes are frequently displaced to facilitate the ability of regulatory proteins to access specific DNA elements. To gain insight into nucleosome dynamics, and to follow how dynamics change during differentiation, we used a technique called time-ChIP to quantitatively assess histone H3.3 turnover genome-wide during differentiation of mouse ESCs. We found that, without prior assumptions, high turnover could be used to identify regions involved in gene regulation. High turnover was seen at enhancers, as observed previously, with particularly high turnover at super-enhancers. In contrast, regions associated with the repressive Polycomb-Group showed low turnover in ESCs. Turnover correlated with DNA accessibility. Upon differentiation, numerous changes in H3.3 turnover rates were observed, the majority of which occurred at enhancers. Thus, time-ChIP measurement of histone turnover shows that active enhancers are unusually dynamic in ESCs and changes in highly dynamic nucleosomes predominate at enhancers during differentiation. DOI: http://dx.doi.org/10.7554/eLife.15316.001 PMID:27304074

Intraband Raman laser gain in a boron nitride coupled quantum well

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

Moorthy, N. Narayana; Peter, A. John, E-mail: a.john.peter@gmail.com

2016-05-23

On-centre impurity related electronic and optical properties are studied in a Boron nitride coupled quantum well. Confined energies for the intraband transition are investigated by studying differential cross section of electron Raman scattering taking into consideration of spatial confinement in a B{sub 0.3}Ga{sub 0.7}N/BN coupled quantum well. Raman gain as a function of incident optical pump intensity is computed for constant well width. The enhancement of Raman gain is observed with the application of pump power. The results can be applied for the potential applications for fabricating some optical devices such as optical switches, infrared photo-detectors and electro-optical modulator.

Enhanced leptin sensitivity and improved glucose homeostasis in mice lacking suppressor of cytokine signaling-3 in POMC-expressing cells.

PubMed

Kievit, Paul; Howard, Jane K; Badman, Michael K; Balthasar, Nina; Coppari, Roberto; Mori, Hiroyuki; Lee, Charlotte E; Elmquist, Joel K; Yoshimura, Akihiko; Flier, Jeffrey S

2006-08-01

Suppressor of cytokine signaling-3 (Socs-3) negatively regulates the action of various cytokines, as well as the metabolic hormones leptin and insulin. Mice with haploinsufficiency of Socs-3, or those with neuronal deletion of Socs-3, are lean and more leptin and insulin sensitive. To examine the role of Socs-3 within specific neurons critical to energy balance, we created mice with selective deletion of Socs-3 within pro-opiomelanocortin (POMC)-expressing cells. These mice had enhanced leptin sensitivity, measured by weight loss and food intake after leptin infusion. On chow diet, glucose homeostasis was improved despite normal weight gain. On a high-fat diet, the rate of weight gain was reduced, due to increased energy expenditure rather than decreased food intake; glucose homeostasis and insulin sensitivity were substantially improved. These studies demonstrate that Socs-3 within POMC neurons regulates leptin sensitivity and glucose homeostasis, and plays a key role in linking high-fat diet to disordered metabolism.

Urea uptake enhances barrier function and antimicrobial defense in humans by regulating epidermal gene expression

PubMed Central

Grether-Beck, Susanne; Felsner, Ingo; Brenden, Heidi; Kohne, Zippora; Majora, Marc; Marini, Alessandra; Jaenicke, Thomas; Rodriguez-Martin, Marina; Trullas, Carles; Hupe, Melanie; Elias, Peter M.; Krutmann, Jean

2012-01-01

Urea is an endogenous metabolite, known to enhance stratum corneum hydration. Yet, topical urea anecdotally also improves permeability barrier function, and it appears to exhibit antimicrobial activity. Hence, we hypothesized that urea is not merely a passive metabolite, but a small-molecule regulator of epidermal structure and function. In 21 human volunteers, topical urea improved barrier function in parallel with enhanced antimicrobial peptide (LL-37 and β-defensin-2) expression. Urea both stimulates expression of, and is transported into keratinocytes by two urea transporters, UT-A1 and UT-A2, and by aquaporin 3, 7 and 9. Inhibitors of these urea transporters block the downstream biological effects of urea, which include increased mRNA and protein levels for: (i) transglutaminase-1, involucrin, loricrin and filaggrin; (ii) epidermal lipid synthetic enzymes, and (iii) cathelicidin/LL-37 and β-defensin-2. Finally, we explored the potential clinical utility of urea, showing that topical urea applications normalized both barrier function and antimicrobial peptide expression in a murine model of atopic dermatitis (AD). Together, these results show that urea is a small-molecule regulator of epidermal permeability barrier function and antimicrobial peptide expression after transporter uptake, followed by gene regulatory activity in normal epidermis, with potential therapeutic applications in diseased skin. PMID:22418868

Power enhanced frequency conversion system

NASA Technical Reports Server (NTRS)

Sanders, Steven (Inventor); Lang, Robert J. (Inventor); Waarts, Robert G. (Inventor)

2001-01-01

A frequency conversion system includes at least one source providing a first near-IR wavelength output including a gain medium for providing high power amplification, such as double clad fiber amplifier, a double clad fiber laser or a semiconductor tapered amplifier to enhance the power output level of the near-IR wavelength output. The NFM device may be a difference frequency mixing (DFM) device or an optical parametric oscillation (OPO) device. Pump powers are gain enhanced by the addition of a rare earth amplifier or oscillator, or a Ra-man/Brillouin amplifier or oscillator between the high power source and the NFM device.

Hepatic Src Homology Phosphatase 2 Regulates Energy Balance in Mice

PubMed Central

Nagata, Naoto; Matsuo, Kosuke; Bettaieb, Ahmed; Bakke, Jesse; Matsuo, Izumi; Graham, James; Xi, Yannan; Liu, Siming; Tomilov, Alexey; Tomilova, Natalia; Gray, Susan; Jung, Dae Young; Ramsey, Jon J.; Kim, Jason K.; Cortopassi, Gino; Havel, Peter J.

2012-01-01

The Src homology 2 domain-containing protein-tyrosine phosphatase Src homology phosphatase 2 (Shp2) is a negative regulator of hepatic insulin action in mice fed regular chow. To investigate the role of hepatic Shp2 in lipid metabolism and energy balance, we determined the metabolic effects of its deletion in mice challenged with a high-fat diet (HFD). We analyzed body mass, lipid metabolism, insulin sensitivity, and glucose tolerance in liver-specific Shp2-deficient mice (referred to herein as LSHKO) and control mice fed HFD. Hepatic Shp2 protein expression is regulated by nutritional status, increasing in mice fed HFD and decreasing during fasting. LSHKO mice gained less weight and exhibited increased energy expenditure compared with control mice. In addition, hepatic Shp2 deficiency led to decreased liver steatosis, enhanced insulin-induced suppression of hepatic glucose production, and impeded the development of insulin resistance after high-fat feeding. At the molecular level, LSHKO exhibited decreased hepatic endoplasmic reticulum stress and inflammation compared with control mice. In addition, tyrosine and serine phosphorylation of total and mitochondrial signal transducer and activator of transcription 3 were enhanced in LSHKO compared with control mice. In line with this observation and the increased energy expenditure of LSHKO, oxygen consumption rate was higher in liver mitochondria of LSHKO compared with controls. Collectively, these studies identify hepatic Shp2 as a novel regulator of systemic energy balance under conditions of high-fat feeding. PMID:22619361

Riverbed Hydrologic Exchange Dynamics in a Large Regulated River Reach

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

Zhou, Tian; Bao, Jie; Huang, Maoyi

Hydrologic exchange flux (HEF) is an important hydrologic component in river corridors that includes both bidirectional (hyporheic) and unidirectional (gaining/losing) surface water – groundwater exchanges. Quantifying HEF rates in a large regulated river is difficult due to the large spatial domains, complexity of geomorphologic features and subsurface properties, and the great stage variations created by dam operations at multiple time scales. In this study, we developed a method that combined numerical modeling and field measurements for estimating HEF rates across the river bed in a 7‐km long reach of the highly regulated Columbia River. A high‐resolution computational fluid dynamics (CFD)more » modeling framework was developed and validated by field measurements and other modeling results to characterize the HEF dynamics across the river bed. We found that about 85% of the time from 2008‐2014 the river was losing water with an annual average net HEF rates across the river bed (Qz) of ‐2.3 m3 s−1 (negative indicating downwelling). June was the only month that the river gained water, with monthly averaged Qz of 0.8 m3 s−1. We also found that the daily dam operations increased the hourly gross gaining and losing rate over an average year of 8% and 2%, respectively. By investigating the HEF feedbacks at various time scales, we suggest that the dam operations could reduce the HEF at seasonal time scale by decreasing the seasonal flow variations, while also enhance the HEF at sub‐daily time scale by generating high frequency discharge variations. These changes could generate significant impacts on biogeochemical processes in the hyporheic zone.« less

Characterization of New Otic Enhancers of the Pou3f4 Gene Reveal Distinct Signaling Pathway Regulation and Spatio-Temporal Patterns

PubMed Central

Robert-Moreno, Àlex; Naranjo, Silvia; de la Calle-Mustienes, Elisa; Gómez-Skarmeta, José Luis; Alsina, Berta

2010-01-01

POU3F4 is a member of the POU-homedomain transcription factor family with a prominent role in inner ear development. Mutations in the human POU3F4 coding unit leads to X-linked deafness type 3 (DFN3), characterized by conductive hearing loss and progressive sensorineural deafness. Microdeletions found 1 Mb 5′ upstream of the coding region also displayed the same phenotype, suggesting that cis-regulatory elements might be present in that region. Indeed, we and others have recently identified several enhancers at the 1 Mb 5′ upstream interval of the pou3f4 locus. Here we characterize the spatio-temporal patterns of these regulatory elements in zebrafish transgenic lines. We show that the most distal enhancer (HCNR 81675) is activated earlier and drives GFP reporter expression initially to a broad ear domain to progressively restrict to the sensory patches. The proximal enhancer (HCNR 82478) is switched later during development and promotes expression, among in other tissues, in sensory patches from its onset. The third enhancer (HCNR 81728) is also active at later stages in the otic mesenchyme and in the otic epithelium. We also characterize the signaling pathways regulating these enhancers. While HCNR 81675 is regulated by very early signals of retinoic acid, HCNR 82478 is regulated by Fgf activity at a later stage and the HCNR 81728 enhancer is under the control of Hh signaling. Finally, we show that Sox2 and Pax2 transcription factors are bound to HCNR 81675 genomic region during otic development and specific mutations to these transcription factor binding sites abrogates HCNR 81675 enhancer activity. Altogether, our results suggest that pou3f4 expression in inner ear might be under the control of distinct regulatory elements that fine-tune the spatio-temporal activity of this gene and provides novel data on the signaling mechanisms controlling pou3f4 function. PMID:21209840

Implicit emotion regulation affects outcome evaluation.

PubMed

Yang, Qiwei; Tang, Ping; Gu, Ruolei; Luo, Wenbo; Luo, Yue-jia

2015-06-01

Efficient implicit emotion regulation processes, which run without awareness, are important for human well-being. In this study, to investigate the influence of implicit emotion regulation on psychological and electrophysiological responses to gains and losses, participants were required to select between two Chinese four-character idioms to match the meaning of the third one before they performed a monetary gambling task. According to whether their meanings were related to emotion regulation, the idioms fell into two categories. Event-related potentials and self-rating emotional experiences to outcome feedback were recorded during the task. Priming emotion regulation reduced subjective emotional experience to both gains and losses and the amplitudes of the feedback-related negativity, while the P3 component was not influenced. According to these results, we suggest that the application of implicit emotion regulation effectively modulated the subjective emotional experience and the motivational salience of current outcomes without the cost of cognitive resources. This study implicates the potential significance of implicit emotion regulation in decision-making processes. © The Author (2014). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

The nuclear cofactor DOR regulates autophagy in mammalian and Drosophila cells.

PubMed

Mauvezin, Caroline; Orpinell, Meritxell; Francis, Víctor A; Mansilla, Francisco; Duran, Jordi; Ribas, Vicent; Palacín, Manuel; Boya, Patricia; Teleman, Aurelio A; Zorzano, Antonio

2010-01-01

The regulation of autophagy in metazoans is only partly understood, and there is a need to identify the proteins that control this process. The diabetes- and obesity-regulated gene (DOR), a recently reported nuclear cofactor of thyroid hormone receptors, is expressed abundantly in metabolically active tissues such as muscle. Here, we show that DOR shuttles between the nucleus and the cytoplasm, depending on cellular stress conditions, and re-localizes to autophagosomes on autophagy activation. We demonstrate that DOR interacts physically with autophagic proteins Golgi-associated ATPase enhancer of 16 kDa (GATE16) and microtubule-associated protein 1A/1B-light chain 3. Gain-of-function and loss-of-function studies indicate that DOR stimulates autophagosome formation and accelerates the degradation of stable proteins. CG11347, the DOR Drosophila homologue, has been predicted to interact with the Drosophila Atg8 homologues, which suggests functional conservation in autophagy. Flies lacking CG11347 show reduced autophagy in the fat body during pupal development. All together, our data indicate that DOR regulates autophagosome formation and protein degradation in mammalian and Drosophila cells.

75 FR 44138 - Build-In Gains and Losses Under Section 382(h); Correction

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-28

... DEPARTMENT OF THE TREASURY Internal Revenue Service 26 CFR Part 1 [TD 9487] RIN 1545-BG03 Build-In.... ACTION: Correcting amendment. SUMMARY: This document contains correcting amends to IRS' regulations providing guidance regarding the treatment of prepaid income under the built-in gain provisions of section...

Developmental gains in visuospatial memory predict gains in mathematics achievement.

PubMed

Li, Yaoran; Geary, David C

2013-01-01

Visuospatial competencies are related to performance in mathematical domains in adulthood, but are not consistently related to mathematics achievement in children. We confirmed the latter for first graders and demonstrated that children who show above average first-to-fifth grade gains in visuospatial memory have an advantage over other children in mathematics. The study involved the assessment of the mathematics and reading achievement of 177 children in kindergarten to fifth grade, inclusive, and their working memory capacity and processing speed in first and fifth grade. Intelligence was assessed in first grade and their second to fourth grade teachers reported on their in-class attentive behavior. Developmental gains in visuospatial memory span (d = 2.4) were larger than gains in the capacity of the central executive (d = 1.6) that in turn were larger than gains in phonological memory span (d = 1.1). First to fifth grade gains in visuospatial memory and in speed of numeral processing predicted end of fifth grade mathematics achievement, as did first grade central executive scores, intelligence, and in-class attentive behavior. The results suggest there are important individual differences in the rate of growth of visuospatial memory during childhood and that these differences become increasingly important for mathematics learning.

Developmental Gains in Visuospatial Memory Predict Gains in Mathematics Achievement

PubMed Central

Li, Yaoran; Geary, David C.

2013-01-01

Visuospatial competencies are related to performance in mathematical domains in adulthood, but are not consistently related to mathematics achievement in children. We confirmed the latter for first graders and demonstrated that children who show above average first-to-fifth grade gains in visuospatial memory have an advantage over other children in mathematics. The study involved the assessment of the mathematics and reading achievement of 177 children in kindergarten to fifth grade, inclusive, and their working memory capacity and processing speed in first and fifth grade. Intelligence was assessed in first grade and their second to fourth grade teachers reported on their in-class attentive behavior. Developmental gains in visuospatial memory span (d = 2.4) were larger than gains in the capacity of the central executive (d = 1.6) that in turn were larger than gains in phonological memory span (d = 1.1). First to fifth grade gains in visuospatial memory and in speed of numeral processing predicted end of fifth grade mathematics achievement, as did first grade central executive scores, intelligence, and in-class attentive behavior. The results suggest there are important individual differences in the rate of growth of visuospatial memory during childhood and that these differences become increasingly important for mathematics learning. PMID:23936154

75 FR 53019 - Proposed Collection; Comment Request for Regulation Project

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-30

... soliciting comments concerning an existing regulation, REG-147144-06, (TD 9446) Section 1.367(a)-8, Gain...: Gain Recognition Agreements With Respect to Certain Transfers of Stock or Securities by United States... Internal Revenue Code (Code) concerning gain recognition agreements filed by United States persons with...

Songs for the Ego: Theorizing Musical Self-Enhancement.

PubMed

Elvers, Paul

2016-01-01

This paper outlines a theoretical account of musical self-enhancement. I claim that listening to music serves as a resource for actively manipulating affective states so that a positive self-view is maintained and a sense of optimism is provided. Self-enhancement-the process by which individuals modify their self-worth and gain self-esteem-typically takes place in social interactions. I argue that experiencing music may serve as a unique "esthetic surrogate" for interaction, which equally enables self-enhancement. This ability relies on three main characteristics of the musical experience, namely, its capacity to (a) evoke empathetic feelings, (b) elicit social cohesion and affiliation, and (c) elicit feelings of reward. I outline how these characteristics relate to theories of music cognition and empirical findings in psychology and neuroscience research. I also explain the specifics of musical self-enhancement and how it differs from music's other regulatory functions such as mood- and emotion regulation. My aim in introducing the notion of musical self-enhancement is to broaden our understanding of how music functions as an environmental resource entailing access to unique affective states and how musical experiences are co-constituted by both the agent and the sonic environment. This specific use of music for self-enhancement can be regarded as a form of affective niche construction, providing the external conditions in which people can experience themselves more positively and maintain high self-esteem.

Gain weighted eigenspace assignment

NASA Technical Reports Server (NTRS)

Davidson, John B.; Andrisani, Dominick, II

1994-01-01

This report presents the development of the gain weighted eigenspace assignment methodology. This provides a designer with a systematic methodology for trading off eigenvector placement versus gain magnitudes, while still maintaining desired closed-loop eigenvalue locations. This is accomplished by forming a cost function composed of a scalar measure of error between desired and achievable eigenvectors and a scalar measure of gain magnitude, determining analytical expressions for the gradients, and solving for the optimal solution by numerical iteration. For this development the scalar measure of gain magnitude is chosen to be a weighted sum of the squares of all the individual elements of the feedback gain matrix. An example is presented to demonstrate the method. In this example, solutions yielding achievable eigenvectors close to the desired eigenvectors are obtained with significant reductions in gain magnitude compared to a solution obtained using a previously developed eigenspace (eigenstructure) assignment method.

Ejector Enhanced Pulsejet Based Pressure Gain Combustors: An Old Idea With a New Twist

NASA Technical Reports Server (NTRS)

Paxson, Daniel E.; Dougherty, Kevin T.

2005-01-01

An experimental investigation of pressure-gain combustion for gas turbine application is described. The test article consists of an off-the-shelf valved pulsejet, and an optimized ejector, both housed within a shroud. The combination forms an effective can combustor across which there is a modest total pressure rise rather than the usual loss found in conventional combustors. Although the concept of using a pulsejet to affect semi-constant volume (i.e., pressure-gain) combustion is not new, that of combining it with a well designed ejector to efficiently mix the bypass flow is. The result is a device which to date has demonstrated an overall pressure rise of approximately 3.5 percent at an overall temperature ratio commensurate with modern gas turbines. This pressure ratio is substantially higher than what has been previously reported in pulsejet-based combustion experiments. Flow non-uniformities in the downstream portion of the device are also shown to be substantially reduced compared to those within the pulsejet itself. The standard deviation of total pressure fluctuations, measured just downstream of the ejector was only 5.0 percent of the mean. This smoothing aspect of the device is critical to turbomachinery applications since turbine performance is, in general, negatively affected by flow non-uniformities and unsteadiness. The experimental rig will be described and details of the performance measurements will be presented. Analyses showing the thermodynamic benefits from this level of pressure-gain performance in a gas turbine will also be assessed for several engine types. Issues regarding practical development of such a device are discussed, as are potential emissions reductions resulting from the rich burning nature of the pulsejet and the rapid mixing (quenching) associated with unsteady ejectors.

What drives sleep-dependent memory consolidation: greater gain or less loss?

PubMed

Fenn, Kimberly M; Hambrick, David Z

2013-06-01

When memory is tested after a delay, performance is typically better if the retention interval includes sleep. However, it is unclear what accounts for this well-established effect. It is possible that sleep enhances the retrieval of information, but it is also possible that sleep protects against memory loss that normally occurs during waking activity. We developed a new research approach to investigate these possibilities. Participants learned a list of paired-associate items and were tested on the items after a 12-h interval that included waking or sleep. We analyzed the number of items gained versus the number of items lost across time. The sleep condition showed more items gained and fewer items lost than did the wake condition. Furthermore, the difference between the conditions (favoring sleep) in lost items was greater than the difference in gain, suggesting that loss prevention may primarily account for the effect of sleep on declarative memory consolidation. This finding may serve as an empirical constraint on theories of memory consolidation.

Accelerating Genetic Gains in Legumes for the Development of Prosperous Smallholder Agriculture: Integrating Genomics, Phenotyping, Systems Modelling and Agronomy.

PubMed

Varshney, Rajeev K; Thudi, Mahendar; Pandey, Manish K; Tardieu, Francois; Ojiewo, Chris; Vadez, Vincent; Whitbread, Anthony M; Siddique, Kadambot H M; Nguyen, Henry T; Carberry, Peter S; Bergvinson, David

2018-03-05

Grain legumes form an important component of the human diet, feed for livestock and replenish soil fertility through biological nitrogen fixation. Globally, the demand for food legumes is increasing as they complement cereals in protein requirements and possess a high percentage of digestible protein. Climate change has enhanced the frequency and intensity of drought stress that is posing serious production constraints, especially in rainfed regions where most legumes are produced. Genetic improvement of legumes, like other crops, is mostly based on pedigree and performance-based selection over the last half century. For achieving faster genetic gains in legumes in rainfed conditions, this review article proposes the integration of modern genomics approaches, high throughput phenomics and simulation modelling as support for crop improvement that leads to improved varieties that perform with appropriate agronomy. Selection intensity, generation interval and improved operational efficiencies in breeding are expected to further enhance the genetic gain in experiment plots. Improved seed access to farmers, combined with appropriate agronomic packages in farmers' fields, will deliver higher genetic gains. Enhanced genetic gains including not only productivity but also nutritional and market traits will increase the profitability of farmers and the availability of affordable nutritious food especially in developing countries.

Measuring learning gain: Comparing anatomy drawing screencasts and paper-based resources.

PubMed

Pickering, James D

2017-07-01

The use of technology-enhanced learning (TEL) resources is now a common tool across a variety of healthcare programs. Despite this popular approach to curriculum delivery there remains a paucity in empirical evidence that quantifies the change in learning gain. The aim of the study was to measure the changes in learning gain observed with anatomy drawing screencasts in comparison to a traditional paper-based resource. Learning gain is a widely used term to describe the tangible changes in learning outcomes that have been achieved after a specific intervention. In regard to this study, a cohort of Year 2 medical students voluntarily participated and were randomly assigned to either a screencast or textbook group to compare changes in learning gain across resource type. Using a pre-test/post-test protocol, and a range of statistical analyses, the learning gain was calculated at three test points: immediate post-test, 1-week post-test and 4-week post-test. Results at all test points revealed a significant increase in learning gain and large effect sizes for the screencast group compared to the textbook group. Possible reasons behind the difference in learning gain are explored by comparing the instructional design of both resources. Strengths and weaknesses of the study design are also considered. This work adds to the growing area of research that supports the effective design of TEL resources which are complimentary to the cognitive theory of multimedia learning to achieve both an effective and efficient learning resource for anatomical education. Anat Sci Educ 10: 307-316. © 2016 American Association of Anatomists. © 2016 American Association of Anatomists.

Impact of Energy Gain and Subsystem Characteristics on Fusion Propulsion Performance

NASA Technical Reports Server (NTRS)

Chakrabarti, S.; Schmidt, G. R.

2001-01-01

Rapid transport of large payloads and human crews throughout the solar system requires propulsion systems having very high specific impulse (I(sub sp) > 10(exp 4) to 10(exp 5) s). It also calls for systems with extremely low mass-power ratios (alpha < 10(exp -1) kg/kW). Such low alpha are beyond the reach of conventional power-limited propulsion, but may be attainable with fusion and other nuclear concepts that produce energy within the propellant. The magnitude of energy gain must be large enough to sustain the nuclear process while still providing a high jet power relative to the massive energy-intensive subsystems associated with these concepts. This paper evaluates the impact of energy gain and subsystem characteristics on alpha. Central to the analysis are general parameters that embody the essential features of any 'gain-limited' propulsion power balance. Results show that the gains required to achieve alpha = 10(exp -1) kg/kW with foreseeable technology range from approximately 100 to over 2000, which is three to five orders of magnitude greater than current fusion state of the arL Sensitivity analyses point to the parameters exerting the most influence for either: (1) lowering a and improving mission performance or (2) relaxing gain requirements and reducing demands on the fusion process. The greatest impact comes from reducing mass and increasing efficiency of the thruster and subsystems downstream of the fusion process. High relative gain, through enhanced fusion processes or more efficient drivers and processors, is also desirable. There is a benefit in improving driver and subsystem characteristics upstream of the fusion process, but it diminishes at relative gains > 100.

Enhancing Decision-Making in STSE Education by Inducing Reflection and Self-Regulated Learning

NASA Astrophysics Data System (ADS)

Gresch, Helge; Hasselhorn, Marcus; Bögeholz, Susanne

2017-02-01

Thoughtful decision-making to resolve socioscientific issues is central to science, technology, society, and environment (STSE) education. One approach for attaining this goal involves fostering students' decision-making processes. Thus, the present study explores whether the application of decision-making strategies, combined with reflections on the decision-making processes of others, enhances decision-making competence. In addition, this study examines whether this process is supported by elements of self-regulated learning, i.e., self-reflection regarding one's own performance and the setting of goals for subsequent tasks. A computer-based training program which involves the resolution of socioscientific issues related to sustainable development was developed in two versions: with and without elements of self-regulated learning. Its effects on decision-making competence were analyzed using a pre test-post test follow-up control-group design ( N = 242 high school students). Decision-making competence was assessed using an open-ended questionnaire that focused on three facets: consideration of advantages and disadvantages, metadecision aspects, and reflection on the decision-making processes of others. The findings suggest that students in both training groups incorporated aspects of metadecision into their statements more often than students in the control group. Furthermore, both training groups were more successful in reflecting on the decision-making processes of others. The students who received additional training in self-regulated learning showed greater benefits in terms of metadecision aspects and reflection, and these effects remained significant two months later. Overall, our findings demonstrate that the application of decision-making strategies, combined with reflections on the decision-making process and elements of self-regulated learning, is a fruitful approach in STSE education.

Surface-Enhanced Raman Scattering Spectroscopy for Label-Free Analysis of P. aeruginosa Quorum Sensing

PubMed Central

Bodelón, Gustavo; Montes-García, Verónica; Pérez-Juste, Jorge; Pastoriza-Santos, Isabel

2018-01-01

Bacterial quorum sensing systems regulate the production of an ample variety of bioactive extracellular compounds that are involved in interspecies microbial interactions and in the interplay between the microbes and their hosts. The development of new approaches for enabling chemical detection of such cellular activities is important in order to gain new insight into their function and biological significance. In recent years, surface-enhanced Raman scattering (SERS) spectroscopy has emerged as an ultrasensitive analytical tool employing rationally designed plasmonic nanostructured substrates. This review highlights recent advances of SERS spectroscopy for label-free detection and imaging of quorum sensing-regulated processes in the human opportunistic pathogen Pseudomonas aeruginosa. We also briefly describe the challenges and limitations of the technique and conclude with a summary of future prospects for the field. PMID:29868499

Sympathetic baroreflex gain in normotensive pregnant women

PubMed Central

Usselman, Charlotte W.; Skow, Rachel J.; Matenchuk, Brittany A.; Chari, Radha S.; Julian, Colleen G.; Stickland, Michael K.; Davenport, Margie H.

2015-01-01

Muscle sympathetic nerve activity is increased during normotensive pregnancy while mean arterial pressure is maintained or reduced, suggesting baroreflex resetting. We hypothesized spontaneous sympathetic baroreflex gain would be reduced in normotensive pregnant women relative to nonpregnant matched controls. Integrated muscle sympathetic burst incidence and total sympathetic activity (microneurography), blood pressure (Finometer), and R-R interval (ECG) were assessed at rest in 11 pregnant women (33 ± 1 wk gestation, 31 ± 1 yr, prepregnancy BMI: 23.5 ± 0.9 kg/m2) and 11 nonpregnant controls (29 ± 1 yr; BMI: 25.2 ± 1.7 kg/m2). Pregnant women had elevated baseline sympathetic burst incidence (43 ± 2 vs. 33 ± 2 bursts/100 heart beats, P = 0.01) and total sympathetic activity (1,811 ± 148 vs. 1,140 ± 55 au, P < 0.01) relative to controls. Both mean (88 ± 3 vs. 91 ± 2 mmHg, P = 0.4) and diastolic (DBP) (72 ± 3 vs. 73 ± 2 mmHg, P = 0.7) pressures were similar between pregnant and nonpregnant women, respectively, indicating an upward resetting of the baroreflex set point with pregnancy. Baroreflex gain, calculated as the linear relationship between sympathetic burst incidence and DBP, was reduced in pregnant women relative to controls (−3.7 ± 0.5 vs. −5.4 ± 0.5 bursts·100 heart beats−1·mmHg−1, P = 0.03), as was baroreflex gain calculated with total sympathetic activity (−294 ± 24 vs. −210 ± 24 au·100 heart beats−1·mmHg−1; P = 0.03). Cardiovagal baroreflex gain (sequence method) was not different between nonpregnant controls and pregnant women (49 ± 8 vs. 36 ± 8 ms/mmHg; P = 0.2). However, sympathetic (burst incidence) and cardiovagal gains were negatively correlated in pregnant women (R = −0.7; P = 0.02). Together, these data indicate that the influence of the sympathetic nervous system over arterial blood pressure is reduced in normotensive pregnancy, in terms of both long-term and beat-to-beat regulation of arterial pressure

Adaptive Gain-based Stable Power Smoothing of a DFIG

DOE PAGES

Muljadi, Eduard; Lee, Hyewon; Hwang, Min; ...

2017-11-01

In a power system that has a high wind penetration, the output power fluctuation of a large-scale wind turbine generator (WTG) caused by the varying wind speed increases the maximum frequency deviation, which is an important metric to assess the quality of electricity, because of the reduced system inertia. This paper proposes a stable power-smoothing scheme of a doubly-fed induction generator (DFIG) that can suppress the maximum frequency deviation, particularly for a power system with a high wind penetration. To do this, the proposed scheme employs an additional control loop relying on the system frequency deviation that operates in combinationmore » with the maximum power point tracking control loop. To improve the power-smoothing capability while guaranteeing the stable operation of a DFIG, the gain of the additional loop is modified with the rotor speed and frequency deviation. The gain is set to be high if the rotor speed and/or frequency deviation is large. Here, the simulation results based on the IEEE 14-bus system demonstrate that the proposed scheme significantly lessens the output power fluctuation of a WTG under various scenarios by modifying the gain with the rotor speed and frequency deviation, and thereby it can regulate the frequency deviation within a narrow range.« less

Adaptive Gain-based Stable Power Smoothing of a DFIG

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

Muljadi, Eduard; Lee, Hyewon; Hwang, Min

In a power system that has a high wind penetration, the output power fluctuation of a large-scale wind turbine generator (WTG) caused by the varying wind speed increases the maximum frequency deviation, which is an important metric to assess the quality of electricity, because of the reduced system inertia. This paper proposes a stable power-smoothing scheme of a doubly-fed induction generator (DFIG) that can suppress the maximum frequency deviation, particularly for a power system with a high wind penetration. To do this, the proposed scheme employs an additional control loop relying on the system frequency deviation that operates in combinationmore » with the maximum power point tracking control loop. To improve the power-smoothing capability while guaranteeing the stable operation of a DFIG, the gain of the additional loop is modified with the rotor speed and frequency deviation. The gain is set to be high if the rotor speed and/or frequency deviation is large. Here, the simulation results based on the IEEE 14-bus system demonstrate that the proposed scheme significantly lessens the output power fluctuation of a WTG under various scenarios by modifying the gain with the rotor speed and frequency deviation, and thereby it can regulate the frequency deviation within a narrow range.« less

Direct molecular regulation of the myogenic determination gene Myf5 by Pax3, with modulation by Six1/4 factors, is exemplified by the -111 kb-Myf5 enhancer.

PubMed

Daubas, Philippe; Buckingham, Margaret E

2013-04-15

The Myf5 gene plays an important role in myogenic determination during mouse embryo development. Multiple genomic regions of the Mrf4-Myf5 locus have been characterised as enhancer sequences responsible for the complex spatiotemporal expression of the Myf5 gene at the onset of myogenesis. These include an enhancer sequence, located at -111 kb upstream of the Myf5 transcription start site, which is responsible of Myf5 activation in ventral somitic domains (Ribas et al., 2011. Dev. Biol. 355, 372-380). We show that the -111 kb-Myf5 enhancer also directs transgene expression in some limb muscles, and is active at foetal as well as embryonic stages. We have carried out further characterisation of the regulation of this enhancer and show that the paired-box Pax3 transcription factor binds to it in vitro as in vivo, and that Pax binding sites are essential for its activity. This requirement is independent of the previously reported regulation by TEAD transcription factors. Six1/4 which, like Pax3, are important upstream regulators of myogenesis, also bind in vivo to sites in the -111 kb-Myf5 enhancer and modulate its activity. The -111 kb-Myf5 enhancer therefore shares common functional characteristics with another Myf5 regulatory sequence, the hypaxial and limb 145 bp-Myf5 enhancer, both being directly regulated in vivo by Pax3 and Six1/4 proteins. However, in the case of the -111 kb-Myf5 enhancer, Six has less effect and we conclude that Pax regulation plays a major role in controlling this aspect of the Myf5 gene expression at the onset of myogenesis in the embryo. Copyright © 2013 Elsevier Inc. All rights reserved.

miR-133b down-regulates ABCC1 and enhances the sensitivity of CRC to anti-tumor drugs.

PubMed

Chen, Miao; Li, Daojiang; Gong, Ni; Wu, Hao; Su, Chen; Xie, Canbin; Xiang, Hong; Lin, Changwei; Li, Xiaorong

2017-08-08

Multidrug resistance (MDR) is the main cause of failed chemotherapy treatments. Therefore, preventing MDR is pivotal in treating colorectal cancer (CRC). In a previous study miR-133b was shown to be a tumor suppressor. Additionally, in CRC cells transfected with miR-133b, ATP-binding cassette (ABC) subfamily C member 1(ABCC1) was shown to be significantly down regulated. Whether miR-133b also enhances the chemosensitivity of drugs used to treat CRC by targeting ABCC1 is still unclear. Here, we utilized flow cytometry and high-performance liquid chromatography (HPLC) analysis to identify the ability of miR-133b to reserve MDR in CRC. We then used a dual-luciferase reporter assay to validate that miR-133b targets ABCC1. Further in vivo experiments were designed to validate the method in which miR-133b reversed MDR in CRC cells. The results demonstrated that the level of miR-133b was down-regulated and the expression of ABCC1 was up-regulated in drug-resistant CRC cells compared to non-drug-resistant CRC cells. The restoration of miR-133b expression in CRC drug-resistant cells in vitro resulted in reduced IC50s to chemotherapeutic drugs, significantly induced G1 accumulation, inhibited growth and promoted necrosis in combination with either 5-fluorouracil (5-FU) or vincristine (VCR), and decreased the expression of ABCC1. The dual-luciferase assay demonstrated that miR-133b directly targets ABCC1. The combination of agomiRNA-133b with chemotherapeutic drugs in vivo inhibited tumor growth induced by CRC drug-resistant cells. A xenograft from the in vivo model resulted in up-regulated levels of miR-133b and down-regulated levels of ABCC1. Therefore, miR-133b enhances the chemosensitivity of CRC cells to anti-tumor drugs by directly down-regulating ABCC1. This discovery provides a therapeutic strategy in which miR-133b is used as a potential sensitizer for drug-resistant CRC.

The Chromatin Remodeler SPLAYED Negatively Regulates SNC1-Mediated Immunity.

PubMed

Johnson, Kaeli C M; Xia, Shitou; Feng, Xiaoqi; Li, Xin

2015-08-01

SNC1 (SUPPRESSOR OF NPR1, CONSTITUTIVE 1) is one of a suite of intracellular Arabidopsis NOD-like receptor (NLR) proteins which, upon activation, result in the induction of defense responses. However, the molecular mechanisms underlying NLR activation and the subsequent provocation of immune responses are only partially characterized. To identify negative regulators of NLR-mediated immunity, a forward genetic screen was undertaken to search for enhancers of the dwarf, autoimmune gain-of-function snc1 mutant. To avoid lethality resulting from severe dwarfism, the screen was conducted using mos4 (modifier of snc1, 4) snc1 plants, which display wild-type-like morphology and resistance. M2 progeny were screened for mutant, snc1-enhancing (muse) mutants displaying a reversion to snc1-like phenotypes. The muse9 mos4 snc1 triple mutant was found to exhibit dwarf morphology, elevated expression of the pPR2-GUS defense marker reporter gene and enhanced resistance to the oomycete pathogen Hyaloperonospora arabidopsidis Noco2. Via map-based cloning and Illumina sequencing, it was determined that the muse9 mutation is in the gene encoding the SWI/SNF chromatin remodeler SYD (SPLAYED), and was thus renamed syd-10. The syd-10 single mutant has no observable alteration from wild-type-like resistance, although the syd-4 T-DNA insertion allele displays enhanced resistance to the bacterial pathogen Pseudomonas syringae pv. maculicola ES4326. Transcription of SNC1 is increased in both syd-4 and syd-10. These data suggest that SYD plays a subtle, specific role in the regulation of SNC1 expression and SNC1-mediated immunity. SYD may work with other proteins at the chromatin level to repress SNC1 transcription; such regulation is important for fine-tuning the expression of NLR-encoding genes to prevent unpropitious autoimmunity. © The Author 2015. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please

Differentiation and Glucocorticoid Regulated Apopto-Phagocytic Gene Expression Patterns in Human Macrophages. Role of Mertk in Enhanced Phagocytosis

PubMed Central

Zahuczky, Gábor; Kristóf, Endre; Majai, Gyöngyike; Fésüs, László

2011-01-01

The daily clearance of physiologically dying cells is performed safely mainly by cells in the mononuclear phagocyte system. They can recognize and engulf dying cells utilizing several cooperative mechanisms. In our study we show that the expression of a broad range of apopto-phagocytic genes is strongly up-regulated during differentiation of human monocytes to macrophages with different donor variability. The glucocorticoid dexamethasone has a profound effect on this process by selectively up-regulating six genes and down-regulating several others. The key role of the up-regulated mer tyrosine kinase (Mertk) in dexamethasone induced enhancement of phagocytosis could be demonstrated in human monocyte derived macrophages by gene silencing as well as blocking antibodies, and also in a monocyte-macrophage like cell line. However, the additional role of other glucocorticoid induced elements must be also considered since the presence of autologous serum during phagocytosis could almost completely compensate for the blocked function of Mertk. PMID:21731712

Identification of a novel protein for memory regulation in the hippocampus.

PubMed

Zhang, Xue-Han; Zhang, Hui; Tu, Yanyang; Gao, Xiang; Zhou, Changfu; Jin, Meilei; Zhao, Guoping; Jing, Naihe; Li, Bao-Ming; Yu, Lei

2005-08-26

Memory formation, maintenance, and retrieval are a dynamic process, reflecting a combined outcome of new memory formation on one hand, and older memory suppression/clearance on the other. Although much knowledge has been gained regarding new memory formation, less is known about the molecular components and processes that serve the function of memory suppression/clearance. Here, we report the identification of a novel protein, termed hippyragranin (HGN), that is expressed in the rat hippocampus and its expression is reduced by hippocampal denervation. Inhibition of HGN by antisense oligonucleotide in area CA1 results in enhanced performance in Morris water maze, as well as elevated long-term potentiation. These results suggest that HGN is involved in negative memory regulation.

Are You Gainfully Employed? Setting Standards for For-Profit Degrees. Education Sector Reports

ERIC Educational Resources Information Center

Miller, Ben

2010-01-01

For-profit higher education institutions have grown by leaps and bounds in recent years, largely free of federal regulation. That freedom would be significantly curtailed if the gainful employment standard takes effect. Vocational training programs would be judged by the ratio of the debt that graduates assume relative to their current earnings…

Systemic Nicotine Increases Gain and Narrows Receptive Fields in A1 via Integrated Cortical and Subcortical Actions.

PubMed

Askew, Caitlin; Intskirveli, Irakli; Metherate, Raju

2017-01-01

Nicotine enhances sensory and cognitive processing via actions at nicotinic acetylcholine receptors (nAChRs), yet the precise circuit- and systems-level mechanisms remain unclear. In sensory cortex, nicotinic modulation of receptive fields (RFs) provides a model to probe mechanisms by which nAChRs regulate cortical circuits. Here, we examine RF modulation in mouse primary auditory cortex (A1) using a novel electrophysiological approach: current-source density (CSD) analysis of responses to tone-in-notched-noise (TINN) acoustic stimuli. TINN stimuli consist of a tone at the characteristic frequency (CF) of the recording site embedded within a white noise stimulus filtered to create a spectral "notch" of variable width centered on CF. Systemic nicotine (2.1 mg/kg) enhanced responses to the CF tone and to narrow-notch stimuli, yet reduced the response to wider-notch stimuli, indicating increased response gain within a narrowed RF. Subsequent manipulations showed that modulation of cortical RFs by systemic nicotine reflected effects at several levels in the auditory pathway: nicotine suppressed responses in the auditory midbrain and thalamus, with suppression increasing with spectral distance from CF so that RFs became narrower, and facilitated responses in the thalamocortical pathway, while nicotinic actions within A1 further contributed to both suppression and facilitation. Thus, multiple effects of systemic nicotine integrate along the ascending auditory pathway. These actions at nAChRs in cortical and subcortical circuits, which mimic effects of auditory attention, likely contribute to nicotinic enhancement of sensory and cognitive processing.

Dexamethasone Treatment Leads to Enhanced Fear Extinction and Dynamic Fkbp5 Regulation in Amygdala

PubMed Central

Sawamura, Takehito; Klengel, Torsten; Armario, Antonio; Jovanovic, Tanja; Norrholm, Seth D; Ressler, Kerry J; Andero, Raül

2016-01-01

Posttraumatic stress disorder (PTSD) is both a prevalent and debilitating trauma-related disorder associated with dysregulated fear learning at the core of many of its signs and symptoms. Improvements in the currently available psychological and pharmacological treatments are needed in order to improve PTSD treatment outcomes and to prevent symptom relapse. In the present study, we used a putative animal model of PTSD that included presentation of immobilization stress (IMO) followed by fear conditioning (FC) a week later. We then investigated the acute effects of GR receptor activation on the extinction (EXT) of conditioned freezing, using dexamethasone administered systemically which is known to result in suppression of the HPA axis. In our previous work, IMO followed by tone-shock-mediated FC was associated with impaired fear EXT. In this study, we administered dexamethasone 4 h before EXT training and then examined EXT retention (RET) 24 h later to determine whether dexamethasone suppression rescued EXT deficits. Dexamethasone treatment produced dose-dependent enhancement of both EXT and RET. Dexamethasone was also associated with reduced amygdala Fkbp5 mRNA expression following EXT and after RET. Moreover, DNA methylation of the Fkbp5 gene occurred in a dose-dependent and time course-dependent manner within the amygdala. Additionally, we found dynamic changes in epigenetic regulation, including Dnmt and Tet gene pathways, as a function of both fear EXT and dexamethasone suppression of the HPA axis. Together, these data suggest that dexamethasone may serve to enhance EXT by altering Fkbp5-mediated glucocorticoid sensitivity via epigenetic regulation of Fkbp5 expression. PMID:26174596

Dexamethasone Treatment Leads to Enhanced Fear Extinction and Dynamic Fkbp5 Regulation in Amygdala.

PubMed

Sawamura, Takehito; Klengel, Torsten; Armario, Antonio; Jovanovic, Tanja; Norrholm, Seth D; Ressler, Kerry J; Andero, Raül

2016-02-01

Posttraumatic stress disorder (PTSD) is both a prevalent and debilitating trauma-related disorder associated with dysregulated fear learning at the core of many of its signs and symptoms. Improvements in the currently available psychological and pharmacological treatments are needed in order to improve PTSD treatment outcomes and to prevent symptom relapse. In the present study, we used a putative animal model of PTSD that included presentation of immobilization stress (IMO) followed by fear conditioning (FC) a week later. We then investigated the acute effects of GR receptor activation on the extinction (EXT) of conditioned freezing, using dexamethasone administered systemically which is known to result in suppression of the HPA axis. In our previous work, IMO followed by tone-shock-mediated FC was associated with impaired fear EXT. In this study, we administered dexamethasone 4 h before EXT training and then examined EXT retention (RET) 24 h later to determine whether dexamethasone suppression rescued EXT deficits. Dexamethasone treatment produced dose-dependent enhancement of both EXT and RET. Dexamethasone was also associated with reduced amygdala Fkbp5 mRNA expression following EXT and after RET. Moreover, DNA methylation of the Fkbp5 gene occurred in a dose-dependent and time course-dependent manner within the amygdala. Additionally, we found dynamic changes in epigenetic regulation, including Dnmt and Tet gene pathways, as a function of both fear EXT and dexamethasone suppression of the HPA axis. Together, these data suggest that dexamethasone may serve to enhance EXT by altering Fkbp5-mediated glucocorticoid sensitivity via epigenetic regulation of Fkbp5 expression.

Dioscin enhances methotrexate absorption by down-regulating MDR1 in vitro and in vivo

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

Wang, Lijuan, E-mail: jlwang1979@163.com; Wang, Changyuan, E-mail: wangcyuan@163.com; Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning, Dalian Medical University, Dalian, Liaoning

2014-06-01

The purpose of this study was to investigate the enhancing effect of dioscin on the absorption of methotrexate (MTX) and clarify the molecular mechanism involved in vivo and in vitro. Dioscin increased MTX chemosensitivity and transepithelial flux in the absorptive direction, significantly inhibiting multidrug resistance 1 (MDR1) mRNA and protein expression and MDR1 promoter and nuclear factor κ-B (NF-κB) activities in Caco-2 cells. Moreover, inhibitor κB-α (IκB-α) degradation was inhibited by dioscin. Dioscin enhanced the intracellular concentration of MTX by down-regulating MDR1 expression through a mechanism that involves NF-κB signaling pathway inhibition in Caco-2 cells. Dioscin strengthened MTX absorption bymore » inhibiting MDR1 expression in rat intestine. In addition, even though MTX is absorbed into the enterocytes, there was no increase in toxicity observed, and that, in fact, decreased toxicity was seen. - Highlights: • Dioscin raised MTX concentration by inhibiting MDR1 in Caco-2 cells. • Dioscin suppresses MDR1 by inhibiting NF-κB signaling pathway in Caco-2 cells. • Dioscin can enhance MTX absorption via inhibiting MDR1 in vivo and in vitro. • Dioscin did not increase MTX-induced gastrointestinal mucosal toxicity.« less

Celecoxib enhances the radiosensitivity of HCT116 cells in a COX-2 independent manner by up-regulating BCCIP

PubMed Central

Xu, Xiao-Ting; Hu, Wen-Tao; Zhou, Ju-Ying; Tu, Yu

2017-01-01

It has been reported that celecoxib, a cyclooxygenase-2 (COX-2)-selective nonsteroidal anti-inflammatory drug (NSAID), regulates the radiosensitivity of several cancer cells. BCCIP (BRCA2 and CDKN1A interacting protein) plays a critical role in maintaining the critical functions of p53 in tumor suppression and response to therapy. However, whether the effect of celecoxib on the radiosensitivity of colorectal cancer (CRC) cells is dependent on BCCIP is largely unclear. In this study, we found that celecoxib enhanced the radiosensitivity of HeLa (a human cervical carcinoma cell line), A549 (a human lung carcinoma cell line), and HCT116 cells (a human CRC cells line). Among these cells, COX-2 expression was undetected in HCT116 cells. Treatment with celecoxib significantly increased BCCIP expression in COX-2 negative HCT116 cells. Knockdown of BCCIP obviously abrogated the enhanced radiosensitivity of HCT116 cells induced by celecoxib. A combination of celecoxib and irradiation treatment induced much more γ-H2AX foci formation, higher levels of radiation injury-related proteins phosphorylation, G2/M arrest, apoptosis, and p53 and p21 expression, and lower levels of Cyclin B1 in HCT116 cells than those in cells treated with irradiation alone. However, these changes were undetected in BCCIP-silenced HCT116 cells. Therefore, these data suggest that BCCIP gene may be a radiosensitivity-related gene in CRC. Celecoxib affects the functions of p53 and inhibits the recovery from the irradiation-induced injury by up-regulating the expression of BCCIP, and subsequently regulates the expressions of genes such as p21 and Cyclin B1 to enhance the radiosensitivity of HCT116 cells in a COX-2 independent manner. PMID:28386336

Enhanced growth of Juniperus thurifera under a warmer climate is explained by a positive carbon gain under cold and drought.

PubMed

Gimeno, Teresa E; Camarero, J Julio; Granda, Elena; Pías, Beatriz; Valladares, Fernando

2012-03-01

Juniperus thurifera L. is an endemic conifer of the western Mediterranean Basin where it is subjected to a severe climatic stress characterized by low winter temperatures and summer drought. Given the trend of increased warming-induced drought stress in this area and the climatic sensitivity of this species, we expect a negative impact of climate change on growth and ecophysiological performance of J. thurifera in the harsh environments where it dominates. To evaluate this, we measured long- and short-term radial growth using dendrochronology, photosynthesis and water-use efficiency in males, females and juveniles in three sites in Central Spain. Climate was monitored and completed with historical records. Mean annual temperature has increased +0.2 °C per decade in the study area, and the main warming trends corresponded to spring (+0.2 °C per decade) and summer (+0.3 °C per decade). Radial growth and maximum photosynthesis peaked in spring and autumn. Positive photosynthetic rates were maintained all year long, albeit at reduced rates in winter and summer. Radial growth was enhanced by wet conditions in the previous autumn and by warm springs and high precipitation in summer of the year of tree-ring formation. Cloud cover during the summer increased growth, while cloudy winters led to impaired carbon gain and reduced growth in the long term. We argue that maintenance of carbon gain under harsh conditions (low winter temperatures and dry summer months) and plastic xylogenesis underlie J. thurifera's ability to profit from changing climatic conditions such as earlier spring onset and erratic summer rainfall. Our results highlight that not only the magnitude but also the sign of the impact of climate change on growth and persistence of Mediterranean trees is species specific.

A L-Band Superstrate Lens Enhanced Antenna and Array for Tactical Operations

DTIC Science & Technology

2013-07-01

unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT The design of a 1.2 GHz microstrip antenna utilizing a superstrate layer for gain enhancement is...CA, 92152-5001 sam.chieh@navy.mil Abstract—The design of a 1.2 GHz microstrip antenna utilizing a superstrate layer for gain enhancement is...realized. The microstrip patch antenna is a widely used antenna in this regime as it is light weight and is easily scalable for increased gains. It has

Songs for the Ego: Theorizing Musical Self-Enhancement

PubMed Central

Elvers, Paul

2016-01-01

This paper outlines a theoretical account of musical self-enhancement. I claim that listening to music serves as a resource for actively manipulating affective states so that a positive self-view is maintained and a sense of optimism is provided. Self-enhancement—the process by which individuals modify their self-worth and gain self-esteem—typically takes place in social interactions. I argue that experiencing music may serve as a unique “esthetic surrogate” for interaction, which equally enables self-enhancement. This ability relies on three main characteristics of the musical experience, namely, its capacity to (a) evoke empathetic feelings, (b) elicit social cohesion and affiliation, and (c) elicit feelings of reward. I outline how these characteristics relate to theories of music cognition and empirical findings in psychology and neuroscience research. I also explain the specifics of musical self-enhancement and how it differs from music’s other regulatory functions such as mood- and emotion regulation. My aim in introducing the notion of musical self-enhancement is to broaden our understanding of how music functions as an environmental resource entailing access to unique affective states and how musical experiences are co-constituted by both the agent and the sonic environment. This specific use of music for self-enhancement can be regarded as a form of affective niche construction, providing the external conditions in which people can experience themselves more positively and maintain high self-esteem. PMID:26834675

Activation of the prefrontal cortex by unilateral transcranial direct current stimulation leads to an asymmetrical effect on risk preference in frames of gain and loss.

PubMed

Ye, Hang; Huang, Daqiang; Wang, Siqi; Zheng, Haoli; Luo, Jun; Chen, Shu

2016-10-01

Previous brain imaging and brain stimulation studies have suggested that the dorsolateral prefrontal cortex may be critical in regulating risk-taking behavior, although its specific causal effect on people's risk preference remains controversial. This paper studied the independent modulation of the activity of the right and left dorsolateral prefrontal cortex using various configurations of transcranial direct current stimulation. We designed a risk-measurement table and adopted a within-subject design to compare the same participant's risk preference before and after unilateral stimulation when presented with different frames of gain and loss. The results confirmed a hemispheric asymmetry and indicated that the right dorsolateral prefrontal cortex has an asymmetric effect on risk preference regarding frames of gain and loss. Enhancing the activity of the right dorsolateral prefrontal cortex significantly decreased the participants' degree of risk aversion in the gain frame, whereas it increased the participants' degree of risk aversion in the loss frame. Our findings provide important information regarding the impact of transcranial direct current stimulation on the risk preference of healthy participants. The effects observed in our experiment compared with those of previous studies provide further evidence of the effects of hemispheric and frame-dependent asymmetry. These findings may be helpful in understanding the neural basis of risk preference in humans, especially when faced with decisions involving possible gain or loss relative to the status quo. Copyright © 2016 Elsevier B.V. All rights reserved.

Interactive, technology-enhanced self-regulated learning tools in healthcare education: a literature review.

PubMed

Petty, Julia

2013-01-01

Learning technology is increasingly being implemented for programmes of blended learning within nurse education. With a growing emphasis on self-directed study particularly in post-basic education, there is a need for learners to be guided in their learning away from practice and limited classroom time. Technology-enabled (TE) tools which engage learners actively can play a part in this. The effectiveness and value of interactive TE learning strategies within healthcare is the focus of this paper. To identify literature that explores the effectiveness of interactive, TE tools on knowledge acquisition and learner satisfaction within healthcare with a view to evaluating their use for post-basic nurse education. A Literature Review was performed focusing on papers exploring the comparative value and perceived benefit of TE tools compared to traditional modes of learning within healthcare. The Databases identified as most suitable due to their relevance to healthcare were accessed through EBSCOhost. Primary, Boolean and advanced searches on key terms were undertaken. Inclusion and exclusion criteria were applied which resulted in a final selection of 11 studies for critique. Analysis of the literature found that knowledge acquisition in most cases was enhanced and measured learner satisfaction was generally positive for interactive, self-regulated TE tools. However, TE education may not suit all learners and this is critiqued in the light of the identified limitations. Interactive self regulation and/or testing can be a valuable learning strategy that can be incorporated into self-directed programmes of study for post-registration learners. Whilst acknowledging the learning styles not suited to such tools, the concurrent use of self-directed TE tools with those learning strategies necessitating a more social presence can work together to support enhancement of knowledge required to deliver rationale for nursing practice. Copyright © 2012 Elsevier Ltd. All rights

34 CFR 462.2 - What regulations apply?

Code of Federal Regulations, 2011 CFR

2011-07-01

... 34 Education 3 2011-07-01 2011-07-01 false What regulations apply? 462.2 Section 462.2 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF VOCATIONAL AND ADULT EDUCATION, DEPARTMENT OF EDUCATION MEASURING EDUCATIONAL GAIN IN THE NATIONAL REPORTING SYSTEM FOR ADULT EDUCATION...

34 CFR 462.2 - What regulations apply?

Code of Federal Regulations, 2010 CFR

2010-07-01

... 34 Education 3 2010-07-01 2010-07-01 false What regulations apply? 462.2 Section 462.2 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF VOCATIONAL AND ADULT EDUCATION, DEPARTMENT OF EDUCATION MEASURING EDUCATIONAL GAIN IN THE NATIONAL REPORTING SYSTEM FOR ADULT EDUCATION...

Recent progress in high gain InAs avalanche photodiodes (Presentation Recording)

NASA Astrophysics Data System (ADS)

Bank, Seth; Maddox, Scott J.; Sun, Wenlu; Nair, Hari P.; Campbell, Joe C.

2015-08-01

InAs possesses nearly ideal material properties for the fabrication of near- and mid-infrared avalanche photodiodes (APDs), which result in strong electron-initiated impact ionization and negligible hole-initiated impact ionization [1]. Consequently, InAs multiplication regions exhibit several appealing characteristics, including extremely low excess noise factors and bandwidth independent of gain [2], [3]. These properties make InAs APDs attractive for a number of near- and mid-infrared sensing applications including remote gas sensing, light detection and ranging (LIDAR), and both active and passive imaging. Here, we discuss our recent advances in the growth and fabrication of high gain, low noise InAs APDs. Devices yielded room temperature multiplication gains >300, with much reduced (~10x) lower dark current densities. We will also discuss a likely key contributor to our current performance limitations: silicon diffusion into the intrinsic (multiplication) region from the underlying n-type layer during growth. Future work will focus on increasing the intrinsic region thickness, targeting gains >1000. This work was supported by the Army Research Office (W911NF-10-1-0391). [1] A. R. J. Marshall, C. H. Tan, M. J. Steer, and J. P. R. David, "Electron dominated impact ionization and avalanche gain characteristics in InAs photodiodes," Applied Physics Letters, vol. 93, p. 111107, 2008. [2] A. R. J. Marshall, A. Krysa, S. Zhang, A. S. Idris, S. Xie, J. P. R. David, and C. H. Tan, "High gain InAs avalanche photodiodes," in 6th EMRS DTC Technical Conference, Edinburgh, Scotland, UK, 2009. [3] S. J. Maddox, W. Sun, Z. Lu, H. P. Nair, J. C. Campbell, and S. R. Bank, "Enhanced low-noise gain from InAs avalanche photodiodes with reduced dark current and background doping," Applied Physics Letters, vol. 101, no. 15, pp. 151124-151124-3, Oct. 2012.

Comparing gains and losses.

PubMed

McGraw, A Peter; Larsen, Jeff T; Kahneman, Daniel; Schkade, David

2010-10-01

Loss aversion in choice is commonly assumed to arise from the anticipation that losses have a greater effect on feelings than gains, but evidence for this assumption in research on judged feelings is mixed. We argue that loss aversion is present in judged feelings when people compare gains and losses and assess them on a common scale. But many situations in which people judge and express their feelings lack these features. When judging their feelings about an outcome, people naturally consider a context of similar outcomes for comparison (e.g., they consider losses against other losses). This process permits gains and losses to be normed separately and produces psychological scale units that may not be the same in size or meaning for gains and losses. Our experiments show loss aversion in judged feelings for tasks that encourage gain-loss comparisons, but not tasks that discourage them, particularly those using bipolar scales.

Pursuit gain and saccadic intrusions in first-degree relatives of probands with schizophrenia.

PubMed

Clementz, B A; Sweeney, J A; Hirt, M; Haas, G

1990-11-01

Oculomotor functioning of 26 probands with schizophrenia, 12 spectrum and 46 nonspectrum first-degree relatives, and 38 nonpsychiatric control subjects was evaluated. Spectrum relatives had more anticipatory saccades (ASs) and lower pursuit gain than nonspectrum relatives, who had more ASs and lower pursuit gain than control subjects. Probands also had lower pursuit gain than nonspectrum relatives and control subjects but did not differ from other groups on AS frequency. Control subjects had more globally accurate pursuit tracking (root mean square [RMS] error deviation) than both relative groups, whereas probands had the poorest RMS scores. Square wave jerk frequency did not differentiate the groups. Attention enhancement affected the frequency of ASs but did not affect either the other intrusive saccadic event or RMS scores. These results offer evidence that eye-movement dysfunction may serve as a biological marker for schizophrenia.

Effectiveness and Student Perceptions of an Active Learning Activity Using a Headline News Story to Enhance In-Class Learning of Cell Cycle Regulation

ERIC Educational Resources Information Center

Dirks-Naylor, Amie J.

2016-01-01

An active learning activity was used to engage students and enhance in-class learning of cell cycle regulation in a PharmD level integrated biological sciences course. The aim of the present study was to determine the effectiveness and perception of the in-class activity. After completion of a lecture on the topic of cell cycle regulation,…

Are gains in decision-making autonomy during early adolescence beneficial for emotional functioning? The case of the United States and china.

PubMed

Qin, Lili; Pomerantz, Eva M; Wang, Qian

2009-01-01

This research examined the role of children's decision-making autonomy in their emotional functioning during early adolescence in the United States and China. Four times over the 7th and 8th grades, 825 American and Chinese children (M = 12.73 years) reported on the extent to which they versus their parents make decisions about issues children often deem as under their authority. Children also reported on their emotional functioning. American children made greater gains over time in decision-making autonomy than did Chinese children. Initial decision-making autonomy predicted enhanced emotional functioning similarly among American and Chinese children. However, gains over time in decision-making autonomy predicted enhanced emotional functioning more in the United States (vs. China) where such gains were normative.

Teacher-Child Relationships, Behavior Regulation, and Language Gain among At-Risk Preschoolers

ERIC Educational Resources Information Center

Schmitt, Mary Beth; Pentimonti, Jill M.; Justice, Laura M.

2012-01-01

Many preschoolers from low socioeconomic-status (SES) backgrounds demonstrate lags in their language development, and preschool participation is viewed as an important means for mitigating these lags. In this study, we investigated how teacher-child relationship quality and children's behavior regulation within preschool classrooms were associated…

Active rc filter permits easy trade-off of amplifier gain and sensitivity to gain

NASA Technical Reports Server (NTRS)

Kerwin, W. J.; Shaffer, C. V.

1968-01-01

Passive RC network was designed with zeros of transmission in the right half of the complex frequency plane in the feedback loop of a simple negative-gain amplifier. The proper positioning provides any desired trade-off between amplifier gain and sensitivity to amplifier gain.

78 FR 6772 - Failure To File Gain Recognition Agreements and Other Required Filings

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-31

... regulations that would amend the existing rules governing the consequences to U.S. persons for failing to file... current law, if a U.S. transferor fails to timely file an initial GRA, or fails to comply in any material... fails to timely file an annual certification), the U.S. transferor is subject to full gain recognition...

Improved Gain Microstrip Patch Antenna

DTIC Science & Technology

2015-08-06

08-2015 Publication Improved Gain Microstrip Patch Antenna David A. Tonn Naval Under Warfare Center Division, Newport 1176 Howell St., Code 00L...GAIN MICROSTRIP PATCH ANTENNA STATEMENT OF GOVERNMENT INTEREST [0001] The invention described herein may be manufactured and used by or for the...patch antenna having increased gain, and an apparatus for increasing the gain and bandwidth of an existing microstrip patch antenna . (2) Description

Electrical stimulation as a biomimicry tool for regulating muscle cell behavior

PubMed Central

Ahadian, Samad; Ostrovidov, Serge; Hosseini, Vahid; Kaji, Hirokazu; Ramalingam, Murugan; Bae, Hojae; Khademhosseini, Ali

2013-01-01

There is a growing need to understand muscle cell behaviors and to engineer muscle tissues to replace defective tissues in the body. Despite a long history of the clinical use of electric fields for muscle tissues in vivo, electrical stimulation (ES) has recently gained significant attention as a powerful tool for regulating muscle cell behaviors in vitro. ES aims to mimic the electrical environment of electroactive muscle cells (e.g., cardiac or skeletal muscle cells) by helping to regulate cell-cell and cell-extracellular matrix (ECM) interactions. As a result, it can be used to enhance the alignment and differentiation of skeletal or cardiac muscle cells and to aid in engineering of functional muscle tissues. Additionally, ES can be used to control and monitor force generation and electrophysiological activity of muscle tissues for bio-actuation and drug-screening applications in a simple, high-throughput, and reproducible manner. In this review paper, we briefly describe the importance of ES in regulating muscle cell behaviors in vitro, as well as the major challenges and prospective potential associated with ES in the context of muscle tissue engineering. PMID:23823664

Electrical stimulation as a biomimicry tool for regulating muscle cell behavior.

PubMed

Ahadian, Samad; Ostrovidov, Serge; Hosseini, Vahid; Kaji, Hirokazu; Ramalingam, Murugan; Bae, Hojae; Khademhosseini, Ali

2013-01-01

There is a growing need to understand muscle cell behaviors and to engineer muscle tissues to replace defective tissues in the body. Despite a long history of the clinical use of electric fields for muscle tissues in vivo, electrical stimulation (ES) has recently gained significant attention as a powerful tool for regulating muscle cell behaviors in vitro. ES aims to mimic the electrical environment of electroactive muscle cells (e.g., cardiac or skeletal muscle cells) by helping to regulate cell-cell and cell-extracellular matrix (ECM) interactions. As a result, it can be used to enhance the alignment and differentiation of skeletal or cardiac muscle cells and to aid in engineering of functional muscle tissues. Additionally, ES can be used to control and monitor force generation and electrophysiological activity of muscle tissues for bio-actuation and drug-screening applications in a simple, high-throughput, and reproducible manner. In this review paper, we briefly describe the importance of ES in regulating muscle cell behaviors in vitro, as well as the major challenges and prospective potential associated with ES in the context of muscle tissue engineering.

A numerical algorithm for optimal feedback gains in high dimensional LQR problems

NASA Technical Reports Server (NTRS)

Banks, H. T.; Ito, K.

1986-01-01

A hybrid method for computing the feedback gains in linear quadratic regulator problems is proposed. The method, which combines the use of a Chandrasekhar type system with an iteration of the Newton-Kleinman form with variable acceleration parameter Smith schemes, is formulated so as to efficiently compute directly the feedback gains rather than solutions of an associated Riccati equation. The hybrid method is particularly appropriate when used with large dimensional systems such as those arising in approximating infinite dimensional (distributed parameter) control systems (e.g., those governed by delay-differential and partial differential equations). Computational advantage of the proposed algorithm over the standard eigenvector (Potter, Laub-Schur) based techniques are discussed and numerical evidence of the efficacy of our ideas presented.

Non-coding RNA derived from the region adjacent to the human HO-1 E2 enhancer selectively regulates HO-1 gene induction by modulating Pol II binding

PubMed Central

Maruyama, Atsushi; Mimura, Junsei; Itoh, Ken

2014-01-01

Recent studies have disclosed the function of enhancer RNAs (eRNAs), which are long non-coding RNAs transcribed from gene enhancer regions, in transcriptional regulation. However, it remains unclear whether eRNAs are involved in the regulation of human heme oxygenase-1 gene (HO-1) induction. Here, we report that multiple nuclear-enriched eRNAs are transcribed from the regions adjacent to two human HO-1 enhancers (i.e. the distal E2 and proximal E1 enhancers), and some of these eRNAs are induced by the oxidative stress-causing reagent diethyl maleate (DEM). We demonstrated that the expression of one forward direction (5′ to 3′) eRNA transcribed from the human HO-1 E2 enhancer region (named human HO-1enhancer RNA E2-3; hereafter called eRNA E2-3) was induced by DEM in an NRF2-dependent manner in HeLa cells. Conversely, knockdown of BACH1, a repressor of HO-1 transcription, further increased DEM-inducible eRNA E2-3 transcription as well as HO-1 expression. In addition, we showed that knockdown of eRNA E2-3 selectively down-regulated DEM-induced HO-1 expression. Furthermore, eRNA E2-3 knockdown attenuated DEM-induced Pol II binding to the promoter and E2 enhancer regions of HO-1 without affecting NRF2 recruitment to the E2 enhancer. These findings indicate that eRNAE2-3 is functional and is required for HO-1 induction. PMID:25404134

76 FR 12415 - Proposed Collection; Comment Request for Regulation Project

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-07

..., Certain Transfers of Property to Regulated Investment Companies (RICs) and Real Estate Investment Trusts... Property to Regulated Investment Companies (RICs) and Real Estate Investment Trusts (REITs). OMB Number... with respect to the net built-in gain of C corporation property that becomes property of a Regulated...

Emotion regulation reduces loss aversion and decreases amygdala responses to losses

PubMed Central

Sokol-Hessner, Peter; Camerer, Colin F.

2013-01-01

Emotion regulation strategies can alter behavioral and physiological responses to emotional stimuli and the neural correlates of those responses in regions such as the amygdala or striatum. The current study investigates the brain systems engaged when using an emotion regulation technique during financial decisions. In decision making, regulating emotion with reappraisal-focused strategies that encourage taking a different perspective has been shown to reduce loss aversion as observed both in choices and in the relative arousal responses to actual loss and gain outcomes. In the current study, we find using fMRI that behavioral loss aversion correlates with amygdala activity in response to losses relative to gains. Success in regulating loss aversion also correlates with the reduction in amygdala responses to losses but not to gains. Furthermore, across both decisions and outcomes, we find the reappraisal strategy increases baseline activity in dorsolateral and ventromedial prefrontal cortex and the striatum. The similarity of the neural circuitry observed to that seen in emotion regulation, despite divergent tasks, serves as further evidence for a role of emotion in decision making, and for the power of reappraisal to change assessments of value and thereby choices. PMID:22275168

Dissecting and engineering of the TetR family regulator SACE_7301 for enhanced erythromycin production in Saccharopolyspora erythraea.

PubMed

Wu, Hang; Chen, Meng; Mao, Yongrong; Li, Weiwei; Liu, Jingtao; Huang, Xunduan; Zhou, Ying; Ye, Bang-Ce; Zhang, Lixin; Weaver, David T; Zhang, Buchang

2014-11-13

Saccharopolyspora erythraea was extensively utilized for the industrial-scale production of erythromycin A (Er-A), a macrolide antibiotic commonly used in human medicine. Yet, S. erythraea lacks regulatory genes in the erythromycin biosynthetic gene (ery) cluster, hampering efforts to enhance Er-A production via the engineering of regulatory genes. By the chromosome gene inactivation technique based on homologous recombination with linearized DNA fragments, we have inactivated a number of candidate TetR family transcriptional regulators (TFRs) and identified one TFR (SACE_7301) positively controlling erythromycin biosynthesis in S. erythraea A226. qRT-PCR and EMSA analyses demonstrated that SACE_7301 activated the transcription of erythromycin biosynthetic gene eryAI and the resistance gene ermE by interacting with their promoter regions with low affinities, similar to BldD (SACE_2077) previously identified to regulate erythromycin biosynthesis and morphological differentiation. Therefore, we designed a strategy for overexpressing SACE_7301 with 1 to 3 extra copies under the control of PermE* in A226. Following up-regulated transcriptional expression of SACE_7301, eryAI and ermE, the SACE_7301-overexpressed strains all increased Er-A production over A226 proportional to the number of copies. Likewise, when SACE_7301 was overexpressed in an industrial S. erythraea WB strain, Er-A yields of the mutants WB/7301, WB/2×7301 and WB/3×7301 were respectively increased by 17%, 29% and 42% relative to that of WB. In a 5 L fermentor, Er-A accumulation increased to 4,230 mg/L with the highest-yield strain WB/3×7301, an approximately 27% production improvement over WB (3,322 mg/L). We have identified and characterized a TFR, SACE_7301, in S. erythraea that positively regulated erythromycin biosynthesis, and overexpression of SACE_7301 in wild-type and industrial S. erythraea strains enhanced Er-A yields. This study markedly improves our understanding of the unusual

Three enhancer regions regulate gbx2 gene expression in the isthmic region during zebrafish development.

PubMed

Islam, Md Ekramul; Kikuta, Hiroshi; Inoue, Fumitaka; Kanai, Maiko; Kawakami, Atsushi; Parvin, Mst Shahnaj; Takeda, Hiroyuki; Yamasu, Kyo

2006-12-01

In vertebrate embryos, positioning of the boundary between the midbrain and hindbrain (MHB) and subsequent isthmus formation are dependent upon the interaction between the Otx2 and Gbx genes. In zebrafish, sequential expression of gbx1 and gbx2 in the anterior hindbrain contributes to this process, whereas in mouse embryos, a single Gbx gene (Gbx2) is responsible for MHB development. In the present study, to investigate the regulatory mechanism of gbx2 in the MHB/isthmic region of zebrafish embryos, we cloned the gene and showed that its organization is conserved among different vertebrates. Promoter analyses revealed three enhancers that direct reporter gene expression after the end of epiboly in the anterior-most hindbrain, which is a feature of the zebrafish gbx2 gene. One of the enhancers is located upstream of gbx2 (AMH1), while the other two enhancers are located downstream of gbx2 (AMH2 and AMH3). Detailed analysis of the AMH1 enhancer showed that it directs expression in the rhombomere 1 (r1) region and the dorsal thalamus, as has been shown for gbx2, whereas no expression was induced by the AMH1 enhancer in other embryonic regions in which gbx2 is expressed. The AMH1 enhancer is composed of multiple regulatory subregions that share the same spatial specificity. The most active of the regulatory subregions is a 291-bp region that contains at least two Pax2-binding sites, both of which are necessary for the function of the main component (PB1-A region) of the AMH1 enhancer. In accordance with these results, enhancer activity in the PB1-A region, as well as gbx2 expression in r1, was missing in no isthmus mutant embryos that lacked functional pax2a. In addition, we identified an upstream conserved sequence of 227bp that suppresses the enhancer activity of AMH1. Taken together, these findings suggest that gbx2 expression during the somitogenesis stage in zebrafish is regulated by a complex mechanism involving Pax2 as well as activators and suppressors in the

Distinct Functions of CCAAT Enhancer-binding Protein Isoforms in the Regulation of Manganese Superoxide Dismutase during Interleukin-1β Stimulation*

PubMed Central

Qiu, Xiaolei; Aiken, Kimberly J.; Chokas, Ann L.; Beachy, Dawn E.; Nick, Harry S.

2008-01-01

The mitochondrial antioxidant enzyme manganese superoxide dismutase (Mn-SOD) is crucial in maintaining cellular and organismal homeostasis. Mn-SOD expression is tightly regulated in a manner that synchronizes its cytoprotective functions during inflammatory challenges. Induction of Mn-SOD gene expression by the proinflammatory cytokine IL-1β is mediated through a complex intronic enhancer element. To identify and characterize the transcription factors required for Mn-SOD enhancer function, a yeast one-hybrid assay was utilized, and two CCAAT enhancer-binding protein (C/EBP) members, C/EBP β and C/EBP δ, were identified. These two transcription factors responded to IL-1β treatment with distinct expression profiles, different temporal yet inducible interactions with the endogenous Mn-SOD enhancer, and also opposite effects on Mn-SOD transcription. C/EBP β is expressed as three isoforms, LAP* (liver-activating protein), LAP, and LIP (liver-inhibitory protein). Our functional analysis demonstrated that only the full-length C/EBP β/LAP* served as a true activator for Mn-SOD, whereas LAP, LIP, and C/EBP δ functioned as potential repressors. Finally, our systematic mutagenesis of the unique N-terminal 21 amino acids further solidified the importance of LAP* in the induction of Mn-SOD and emphasized the crucial role of this isoform. Our data demonstrating the physiological relevance of the N-terminal peptide also provide a rationale for revisiting the role of LAP* in the regulation of other genes and in pathways such as lipogenesis and development. PMID:18559338

An epigenetic switch regulates de novo DNA methylation at a subset of pluripotency gene enhancers during embryonic stem cell differentiation

PubMed Central

Petell, Christopher J.; Alabdi, Lama; He, Ming; San Miguel, Phillip; Rose, Richard; Gowher, Humaira

2016-01-01

Coordinated regulation of gene expression that involves activation of lineage specific genes and repression of pluripotency genes drives differentiation of embryonic stem cells (ESC). For complete repression of pluripotency genes during ESC differentiation, chromatin at their enhancers is silenced by the activity of the Lsd1-Mi2/NuRD complex. The mechanism/s that regulate DNA methylation at these enhancers are largely unknown. Here, we investigated the affect of the Lsd1-Mi2/NuRD complex on the dynamic regulatory switch that induces the local interaction of histone tails with the Dnmt3 ATRX-DNMT3-DNMT3L (ADD) domain, thus promoting DNA methylation at the enhancers of a subset of pluripotency genes. This is supported by previous structural studies showing a specific interaction between Dnmt3-ADD domain with H3K4 unmethylated histone tails that is disrupted by histone H3K4 methylation and histone acetylation. Our data suggest that Dnmt3a activity is triggered by Lsd1-Mi2/NuRD-mediated histone deacetylation and demethylation at these pluripotency gene enhancers when they are inactivated during mouse ESC differentiation. Using Dnmt3 knockout ESCs and the inhibitors of Lsd1 and p300 histone modifying enzymes during differentiation of E14Tg2A and ZHBTc4 ESCs, our study systematically reveals this mechanism and establishes that Dnmt3a is both reader and effector of the epigenetic state at these target sites. PMID:27179026

Association of gestational weight gain expectations with advice on actual weight gain

USDA-ARS?s Scientific Manuscript database

To examine pregnant women's gestational weight gain expectations/advice from various sources (i.e., self, family/friends, physician) and the impact of these sources of expectations/advice on actual measured gestational weight gain. Pregnant women (n=230, 87.4% Caucasian, second pregnancy) in a cohor...

Effects of Collaborative Group Composition and Inquiry Instruction on Reasoning Gains and Achievement in Undergraduate Biology

PubMed Central

Jensen, Jamie Lee; Lawson, Anton

2011-01-01

This study compared the effectiveness of collaborative group composition and instructional method on reasoning gains and achievement in college biology. Based on initial student reasoning ability (i.e., low, medium, or high), students were assigned to either homogeneous or heterogeneous collaborative groups within either inquiry or didactic instruction. Achievement and reasoning gains were assessed at the end of the semester. Inquiry instruction, as a whole, led to significantly greater gains in reasoning ability and achievement. Inquiry instruction also led to greater confidence and more positive attitudes toward collaboration. Low-reasoning students made significantly greater reasoning gains within inquiry instruction when grouped with other low reasoners than when grouped with either medium or high reasoners. Results are consistent with equilibration theory, supporting the idea that students benefit from the opportunity for self-regulation without the guidance or direction of a more capable peer. PMID:21364101

Weight Gain during Pregnancy

MedlinePlus

... Global Map Premature Birth Report Cards Careers Archives Pregnancy Before or between pregnancies Nutrition, weight & fitness Prenatal ... fitness > Weight gain during pregnancy Weight gain during pregnancy E-mail to a friend Please fill in ...

Asthma Triggers: Gain Control

MedlinePlus

... Centers Asthma Contact Us Share Asthma Triggers: Gain Control Breathing Freely: Controlling Asthma Triggers This video features ... Air Quality: Biological Pollutants Help Your Child Gain Control Over Asthma Top of Page Molds About Molds ...

Parity-time-symmetry enhanced optomechanically-induced-transparency

PubMed Central

Li, Wenlin; Jiang, Yunfeng; Li, Chong; Song, Heshan

2016-01-01

We propose and analyze a scheme to enhance optomechanically-induced-transparency (OMIT) based on parity-time-symmetric optomechanical system. Our results predict that an OMIT window which does not exist originally can appear in weak optomechanical coupling and driving system via coupling an auxiliary active cavity with optical gain. This phenomenon is quite different from these reported in previous works in which the gain is considered just to damage OMIT phenomenon even leads to electromagnetically induced absorption or inverted-OMIT. Such enhanced OMIT effects are ascribed to the additional gain which can increase photon number in cavity without reducing effective decay. We also discuss the scheme feasibility by analyzing recent experiment parameters. Our work provide a promising platform for the coherent manipulation and slow light operation, which has potential applications for quantum information processing and quantum optical device. PMID:27489193

Estrogen suppresses melatonin-enhanced hyperactivation of hamster spermatozoa

PubMed Central

FUJINOKI, Masakatsu; TAKEI, Gen L.

2015-01-01

Hamster sperm hyperactivation is enhanced by progesterone, and this progesterone-enhanced hyperactivation is suppressed by 17β-estradiol (17βE2) and γ-aminobutyric acid (GABA). Although it has been indicated that melatonin also enhances hyperactivation, it is unknown whether melatonin-enhanced hyperactivation is also suppressed by 17βE2 and GABA. In the present study, melatonin-enhanced hyperactivation was significantly suppressed by 17βE2 but not by GABA. Moreover, suppression of melatonin-enhanced hyperactivation by 17βE2 occurred through non-genomic regulation via the estrogen receptor (ER). These results suggest that enhancement of hyperactivation is regulated by melatonin and 17βE2 through non-genomic regulation. PMID:25959801

Water quality in Gaines Creek and Gaines Creek arm of Eufaula Lake, Oklahoma

USGS Publications Warehouse

Kurklin, J.K.

1990-01-01

Based on samples collected from May 1978 to May 1980 and analyzed for major anions, nitrogen, trace elements, phytoplankton, and bacteria, the water in Gaines Creek and the Gaines Creek arm of Eufaula Lake was similar with respect to suitability for municipal use. Water from Gaines Creek had a pH range of 5.7 to 7.6 and a maximum specific conductance of 97 microsiemens per centimeter at 25o Celsius, whereas water from the Gaines Creek arm of Eufaula Lake had a pH range of 6.0 to 9.2 and a maximum specific conductance of 260 microsiemens per centimeter at 25o Celsius. Dissolved oxygen, pH, temperature, and specific conductance values for the lake varied with depth. With the exceptions of cadmium, iron, lead, and manganese, trace-element determinations of samples were within recommended national primary and secondary drinking-water standards. When compared to the National Academy of Sciences water-quality criteria, phytoplankton and bacteria counts exceeded recommendations; however, water from either Gaines Creek or Eufaula Lake could be treated similarly and used as a municipal water supply.

Image contrast enhancement based on a local standard deviation model

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

Chang, Dah-Chung; Wu, Wen-Rong

1996-12-31

The adaptive contrast enhancement (ACE) algorithm is a widely used image enhancement method, which needs a contrast gain to adjust high frequency components of an image. In the literature, the gain is usually inversely proportional to the local standard deviation (LSD) or is a constant. But these cause two problems in practical applications, i.e., noise overenhancement and ringing artifact. In this paper a new gain is developed based on Hunt`s Gaussian image model to prevent the two defects. The new gain is a nonlinear function of LSD and has the desired characteristic emphasizing the LSD regions in which details aremore » concentrated. We have applied the new ACE algorithm to chest x-ray images and the simulations show the effectiveness of the proposed algorithm.« less

Systemic Nicotine Increases Gain and Narrows Receptive Fields in A1 via Integrated Cortical and Subcortical Actions

PubMed Central

Intskirveli, Irakli

2017-01-01

Abstract Nicotine enhances sensory and cognitive processing via actions at nicotinic acetylcholine receptors (nAChRs), yet the precise circuit- and systems-level mechanisms remain unclear. In sensory cortex, nicotinic modulation of receptive fields (RFs) provides a model to probe mechanisms by which nAChRs regulate cortical circuits. Here, we examine RF modulation in mouse primary auditory cortex (A1) using a novel electrophysiological approach: current-source density (CSD) analysis of responses to tone-in-notched-noise (TINN) acoustic stimuli. TINN stimuli consist of a tone at the characteristic frequency (CF) of the recording site embedded within a white noise stimulus filtered to create a spectral “notch” of variable width centered on CF. Systemic nicotine (2.1 mg/kg) enhanced responses to the CF tone and to narrow-notch stimuli, yet reduced the response to wider-notch stimuli, indicating increased response gain within a narrowed RF. Subsequent manipulations showed that modulation of cortical RFs by systemic nicotine reflected effects at several levels in the auditory pathway: nicotine suppressed responses in the auditory midbrain and thalamus, with suppression increasing with spectral distance from CF so that RFs became narrower, and facilitated responses in the thalamocortical pathway, while nicotinic actions within A1 further contributed to both suppression and facilitation. Thus, multiple effects of systemic nicotine integrate along the ascending auditory pathway. These actions at nAChRs in cortical and subcortical circuits, which mimic effects of auditory attention, likely contribute to nicotinic enhancement of sensory and cognitive processing. PMID:28660244

Novel signal transducer and activator of transcription 1 mutation disrupts small ubiquitin-related modifier conjugation causing gain of function.

PubMed

Sampaio, Elizabeth P; Ding, Li; Rose, Stacey R; Cruz, Phillip; Hsu, Amy P; Kashyap, Anuj; Rosen, Lindsey B; Smelkinson, Margery; Tavella, Tatyana A; Ferre, Elise M N; Wierman, Meredith K; Zerbe, Christa S; Lionakis, Michail S; Holland, Steven M

2018-05-01

Sumoylation is a posttranslational reversible modification of cellular proteins through the conjugation of small ubiquitin-related modifier (SUMO) and comprises an important regulator of protein function. We sought to characterize the molecular mechanism of a novel mutation at the SUMO motif on signal transducer and activator of transcription 1 (STAT1). STAT1 sequencing and functional characterization were performed in transfection experiments by using immunoblotting and immunoprecipitation in STAT1-deficient cell lines. Transcriptional response and target gene activation were also investigated in PBMCs. We identified a novel STAT1 mutation (c.2114A>T, p.E705V) within the SUMO motif ( 702 IKTE 705 ) in a patient with disseminated Rhodococcus species infection, Norwegian scabies, chronic mucocutaneous candidiasis, hypothyroidism, and esophageal squamous cell carcinoma. The mutation is located in the tail segment and is predicted to disrupt STAT1 sumoylation. Immunoprecipitation experiments performed in transfected cells confirmed absent STAT1 sumoylation for E705V, whereas it was present in wild-type (WT) STAT1 cells, as well as the loss-of-function mutants L706S and Y701C. Furthermore, stimulation with IFN-γ led to enhanced STAT1 phosphorylation, enhanced transcriptional activity, and target gene expression in the E705V-transfected compared with WT-transfected cells. Computer modeling of WT and mutant STAT1 molecules showed variations in the accessibility of the phosphorylation site Y701, which corresponded to the loss-of-function and gain-of-function variants. This is the first report of a mutation in the STAT1 sumoylation motif associated with clinical disease. These data reinforce sumoylation as a key posttranslational regulatory modification of STAT1 and identify a novel mechanism for gain-of-function STAT1 disease in human subjects. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. All rights reserved.

Social Gains from Female Education: A Cross-National Study. World Bank Discussion Papers 194.

ERIC Educational Resources Information Center

Subbarao, K.; Raney, Laura

This paper on the social gains from female education is part of a series, prepared by the World Bank, on the benefits of improving opportunities for women. The paper suggests that expanding women's opportunities enhances their productivity and earning potential and thus contributes to better economic performance and poverty alleviation. Education…

Neuronal plasticity in hibernation and the proposed role of the microtubule-associated protein tau as a "master switch" regulating synaptic gain in neuronal networks.

PubMed

Arendt, Thomas; Bullmann, Torsten

2013-09-01

The present paper provides an overview of adaptive changes in brain structure and learning abilities during hibernation as a behavioral strategy used by several mammalian species to minimize energy expenditure under current or anticipated inhospitable environmental conditions. One cellular mechanism that contributes to the regulated suppression of metabolism and thermogenesis during hibernation is reversible phosphorylation of enzymes and proteins, which limits rates of flux through metabolic pathways. Reversible phosphorylation during hibernation also affects synaptic membrane proteins, a process known to be involved in synaptic plasticity. This mechanism of reversible protein phosphorylation also affects the microtubule-associated protein tau, thereby generating a condition that in the adult human brain is associated with aggregation of tau protein to paired helical filaments (PHFs), as observed in Alzheimer's disease. Here, we put forward the concept that phosphorylation of tau is a neuroprotective mechanism to escape NMDA-mediated hyperexcitability of neurons that would otherwise occur during slow gradual cooling of the brain. Phosphorylation of tau and its subsequent targeting to subsynaptic sites might, thus, work as a kind of "master switch," regulating NMDA receptor-mediated synaptic gain in a wide array of neuronal networks, thereby enabling entry into torpor. If this condition lasts too long, however, it may eventually turn into a pathological trigger, driving a cascade of events leading to neurodegeneration, as in Alzheimer's disease or other "tauopathies".

Improved Drain Current Saturation and Voltage Gain in Graphene-on-Silicon Field Effect Transistors.

PubMed

Song, Seung Min; Bong, Jae Hoon; Hwang, Wan Sik; Cho, Byung Jin

2016-05-04

Graphene devices for radio frequency (RF) applications are of great interest due to their excellent carrier mobility and saturation velocity. However, the insufficient current saturation in graphene field effect transistors (FETs) is a barrier preventing enhancements of the maximum oscillation frequency and voltage gain, both of which should be improved for RF transistors. Achieving a high output resistance is therefore a crucial step for graphene to be utilized in RF applications. In the present study, we report high output resistances and voltage gains in graphene-on-silicon (GoS) FETs. This is achieved by utilizing bare silicon as a supporting substrate without an insulating layer under the graphene. The GoSFETs exhibit a maximum output resistance of 2.5 MΩ∙μm, maximum intrinsic voltage gain of 28 dB, and maximum voltage gain of 9 dB. This method opens a new route to overcome the limitations of conventional graphene-on-insulator (GoI) FETs and subsequently brings graphene electronics closer to practical usage.

Improved Drain Current Saturation and Voltage Gain in Graphene–on–Silicon Field Effect Transistors

PubMed Central

Song, Seung Min; Bong, Jae Hoon; Hwang, Wan Sik; Cho, Byung Jin

2016-01-01

Graphene devices for radio frequency (RF) applications are of great interest due to their excellent carrier mobility and saturation velocity. However, the insufficient current saturation in graphene field effect transistors (FETs) is a barrier preventing enhancements of the maximum oscillation frequency and voltage gain, both of which should be improved for RF transistors. Achieving a high output resistance is therefore a crucial step for graphene to be utilized in RF applications. In the present study, we report high output resistances and voltage gains in graphene-on-silicon (GoS) FETs. This is achieved by utilizing bare silicon as a supporting substrate without an insulating layer under the graphene. The GoSFETs exhibit a maximum output resistance of 2.5 MΩ∙μm, maximum intrinsic voltage gain of 28 dB, and maximum voltage gain of 9 dB. This method opens a new route to overcome the limitations of conventional graphene-on-insulator (GoI) FETs and subsequently brings graphene electronics closer to practical usage. PMID:27142861

Leading Gainful Employment Metric Reporting

ERIC Educational Resources Information Center

Powers, Kristina; MacPherson, Derek

2016-01-01

This chapter will address the importance of intercampus involvement in reporting of gainful employment student-level data that will be used in the calculation of gainful employment metrics by the U.S. Department of Education. The authors will discuss why building relationships within the institution is critical for effective gainful employment…

Mutations in epigenetic regulators including SETD2 are gained during relapse in paediatric acute lymphoblastic leukaemia.

PubMed

Mar, Brenton G; Bullinger, Lars B; McLean, Kathleen M; Grauman, Peter V; Harris, Marian H; Stevenson, Kristen; Neuberg, Donna S; Sinha, Amit U; Sallan, Stephen E; Silverman, Lewis B; Kung, Andrew L; Lo Nigro, Luca; Ebert, Benjamin L; Armstrong, Scott A

2014-03-24

Relapsed paediatric acute lymphoblastic leukaemia (ALL) has high rates of treatment failure. Epigenetic regulators have been proposed as modulators of chemoresistance, here, we sequence genes encoding epigenetic regulators in matched diagnosis-remission-relapse ALL samples. We find significant enrichment of mutations in epigenetic regulators at relapse with recurrent somatic mutations in SETD2, CREBBP, MSH6, KDM6A and MLL2, mutations in signalling factors are not enriched. Somatic alterations in SETD2, including frameshift and nonsense mutations, are present at 12% in a large de novo ALL patient cohort. We conclude that the enrichment of mutations in epigenetic regulators at relapse is consistent with a role in mediating therapy resistance.

Alternative growth promoters alter broiler gut microbiome and enhance body weight gain

USDA-ARS?s Scientific Manuscript database

Antibiotic growth promoters (AGPs) have commonly been used to enhance growth in poultry production. However, there has been increasing concern over the impact of AGPs use in food production on acquisition of antibiotic resistance in zoonotic bacterial pathogens through inter-bacterial transfer of an...

Elevated CO2 stimulates marsh elevation gain, counterbalancing sea-level rise

USGS Publications Warehouse

Langley, J.A.; McKee, K.L.; Cahoon, D.R.; Cherry, J.A.; Megonigala, J.P.

2009-01-01

Tidal wetlands experiencing increased rates of sea-level rise (SLR) must increase rates of soil elevation gain to avoid permanent conversion to open water. The maximal rate of SLR that these ecosystems can tolerate depends partly on mineral sediment deposition, but the accumulation of organic matter is equally important for many wetlands. Plant productivity drives organic matter dynamics and is sensitive to global change factors, such as rising atmospheric CO2 concentration. It remains unknown how global change will influence organic mechanisms that determine future tidal wetland viability. Here, we present experimental evidence that plant response to elevated atmospheric [CO2] stimulates biogenic mechanisms of elevation gain in a brackish marsh. Elevated CO2 (ambient + 340 ppm) accelerated soil elevation gain by 3.9 mm yr−1in this 2-year field study, an effect mediated by stimulation of below-ground plant productivity. Further, a companion greenhouse experiment revealed that the CO2 effect was enhanced under salinity and flooding conditions likely to accompany future SLR. Our results indicate that by stimulating biogenic contributions to marsh elevation, increases in the greenhouse gas, CO2, may paradoxically aid some coastal wetlands in counterbalancing rising seas.

Elevated CO2 stimulates marsh elevation gain, counterbalancing sea-level rise.

PubMed

Langley, J Adam; McKee, Karen L; Cahoon, Donald R; Cherry, Julia A; Megonigal, J Patrick

2009-04-14

Tidal wetlands experiencing increased rates of sea-level rise (SLR) must increase rates of soil elevation gain to avoid permanent conversion to open water. The maximal rate of SLR that these ecosystems can tolerate depends partly on mineral sediment deposition, but the accumulation of organic matter is equally important for many wetlands. Plant productivity drives organic matter dynamics and is sensitive to global change factors, such as rising atmospheric CO(2) concentration. It remains unknown how global change will influence organic mechanisms that determine future tidal wetland viability. Here, we present experimental evidence that plant response to elevated atmospheric [CO(2)] stimulates biogenic mechanisms of elevation gain in a brackish marsh. Elevated CO(2) (ambient + 340 ppm) accelerated soil elevation gain by 3.9 mm yr(-1) in this 2-year field study, an effect mediated by stimulation of below-ground plant productivity. Further, a companion greenhouse experiment revealed that the CO(2) effect was enhanced under salinity and flooding conditions likely to accompany future SLR. Our results indicate that by stimulating biogenic contributions to marsh elevation, increases in the greenhouse gas, CO(2), may paradoxically aid some coastal wetlands in counterbalancing rising seas.

Elevated CO2 stimulates marsh elevation gain, counterbalancing sea-level rise

PubMed Central

Langley, J. Adam; McKee, Karen L.; Cahoon, Donald R.; Cherry, Julia A.; Megonigal, J. Patrick

2009-01-01

Tidal wetlands experiencing increased rates of sea-level rise (SLR) must increase rates of soil elevation gain to avoid permanent conversion to open water. The maximal rate of SLR that these ecosystems can tolerate depends partly on mineral sediment deposition, but the accumulation of organic matter is equally important for many wetlands. Plant productivity drives organic matter dynamics and is sensitive to global change factors, such as rising atmospheric CO2 concentration. It remains unknown how global change will influence organic mechanisms that determine future tidal wetland viability. Here, we present experimental evidence that plant response to elevated atmospheric [CO2] stimulates biogenic mechanisms of elevation gain in a brackish marsh. Elevated CO2 (ambient + 340 ppm) accelerated soil elevation gain by 3.9 mm yr−1 in this 2-year field study, an effect mediated by stimulation of below-ground plant productivity. Further, a companion greenhouse experiment revealed that the CO2 effect was enhanced under salinity and flooding conditions likely to accompany future SLR. Our results indicate that by stimulating biogenic contributions to marsh elevation, increases in the greenhouse gas, CO2, may paradoxically aid some coastal wetlands in counterbalancing rising seas. PMID:19325121

Regulation of the glucocorticoid receptor via a BET-dependent enhancer drives antiandrogen resistance in prostate cancer.

PubMed

Shah, Neel; Wang, Ping; Wongvipat, John; Karthaus, Wouter R; Abida, Wassim; Armenia, Joshua; Rockowitz, Shira; Drier, Yotam; Bernstein, Bradley E; Long, Henry W; Freedman, Matthew L; Arora, Vivek K; Zheng, Deyou; Sawyers, Charles L

2017-09-11

In prostate cancer, resistance to the antiandrogen enzalutamide (Enz) can occur through bypass of androgen receptor (AR) blockade by the glucocorticoid receptor (GR). In contrast to fixed genomic alterations, here we show that GR-mediated antiandrogen resistance is adaptive and reversible due to regulation of GR expression by a tissue-specific enhancer. GR expression is silenced in prostate cancer by a combination of AR binding and EZH2-mediated repression at the GR locus, but is restored in advanced prostate cancers upon reversion of both repressive signals. Remarkably, BET bromodomain inhibition resensitizes drug-resistant tumors to Enz by selectively impairing the GR signaling axis via this enhancer. In addition to revealing an underlying molecular mechanism of GR-driven drug resistance, these data suggest that inhibitors of broadly active chromatin-readers could have utility in nuanced clinical contexts of acquired drug resistance with a more favorable therapeutic index.

A Novel Approach to Noise-Filtering Based on a Gain-Scheduling Neural Network Architecture

NASA Technical Reports Server (NTRS)

Troudet, T.; Merrill, W.

1994-01-01

A gain-scheduling neural network architecture is proposed to enhance the noise-filtering efficiency of feedforward neural networks, in terms of both nominal performance and robustness. The synergistic benefits of the proposed architecture are demonstrated and discussed in the context of the noise-filtering of signals that are typically encountered in aerospace control systems. The synthesis of such a gain-scheduled neurofiltering provides the robustness of linear filtering, while preserving the nominal performance advantage of conventional nonlinear neurofiltering. Quantitative performance and robustness evaluations are provided for the signal processing of pitch rate responses to typical pilot command inputs for a modern fighter aircraft model.

SET1A/COMPASS and shadow enhancers in the regulation of homeotic gene expression

PubMed Central

Cao, Kaixiang; Collings, Clayton K.; Marshall, Stacy A.; Morgan, Marc A.; Rendleman, Emily J.; Wang, Lu; Sze, Christie C.; Sun, Tianjiao; Bartom, Elizabeth T.; Shilatifard, Ali

2017-01-01

The homeotic (Hox) genes are highly conserved in metazoans, where they are required for various processes in development, and misregulation of their expression is associated with human cancer. In the developing embryo, Hox genes are activated sequentially in time and space according to their genomic position within Hox gene clusters. Accumulating evidence implicates both enhancer elements and noncoding RNAs in controlling this spatiotemporal expression of Hox genes, but disentangling their relative contributions is challenging. Here, we identify two cis-regulatory elements (E1 and E2) functioning as shadow enhancers to regulate the early expression of the HoxA genes. Simultaneous deletion of these shadow enhancers in embryonic stem cells leads to impaired activation of HoxA genes upon differentiation, while knockdown of a long noncoding RNA overlapping E1 has no detectable effect on their expression. Although MLL/COMPASS (complex of proteins associated with Set1) family of histone methyltransferases is known to activate transcription of Hox genes in other contexts, we found that individual inactivation of the MLL1-4/COMPASS family members has little effect on early Hox gene activation. Instead, we demonstrate that SET1A/COMPASS is required for full transcriptional activation of multiple Hox genes but functions independently of the E1 and E2 cis-regulatory elements. Our results reveal multiple regulatory layers for Hox genes to fine-tune transcriptional programs essential for development. PMID:28487406

Leishmania donovani chaperonin 10 regulates parasite internalization and intracellular survival in human macrophages.

PubMed

Colineau, Lucie; Clos, Joachim; Moon, Kyung-Mee; Foster, Leonard J; Reiner, Neil E

2017-06-01

Protozoa of the genus Leishmania infect macrophages in their mammalian hosts causing a spectrum of diseases known as the leishmaniases. The search for leishmania effectors that support macrophage infection is a focus of significant interest. One such candidate is leishmania chaperonin 10 (CPN10) which is secreted in exosomes and may have immunosuppressive properties. Here, we report for the first time that leishmania CPN10 localizes to the cytosol of infected macrophages. Next, we generated two genetically modified strains of Leishmania donovani (Ld): one strain overexpressing CPN10 (CPN10+++) and the second, a CPN10 single allele knockdown (CPN10+/-), as the null mutant was lethal. When compared with the wild-type (WT) parental strain, CPN10+/- Ld showed higher infection rates and parasite loads in human macrophages after 24 h of infection. Conversely, CPN10+++ Ld was associated with lower initial infection rates. This unexpected apparent gain-of-function for the knockdown could have been explained either by enhanced parasite internalization or by enhanced intracellular survival. Paradoxically, we found that CPN10+/- leishmania were more readily internalized than WT Ld, but also displayed significantly impaired intracellular survival. This suggests that leishmania CPN10 negatively regulates the rate of parasite uptake by macrophages while being required for intracellular survival. Finally, quantitative proteomics identified an array of leishmania proteins whose expression was positively regulated by CPN10. In contrast, many macrophage proteins involved in innate immunity were negatively regulated by CPN10. Taken together, these findings identify leishmania CPN10 as a novel effector with broad based effects on macrophage cell regulation and parasite survival.

An epigenetic switch regulates de novo DNA methylation at a subset of pluripotency gene enhancers during embryonic stem cell differentiation.

PubMed

Petell, Christopher J; Alabdi, Lama; He, Ming; San Miguel, Phillip; Rose, Richard; Gowher, Humaira

2016-09-19

Coordinated regulation of gene expression that involves activation of lineage specific genes and repression of pluripotency genes drives differentiation of embryonic stem cells (ESC). For complete repression of pluripotency genes during ESC differentiation, chromatin at their enhancers is silenced by the activity of the Lsd1-Mi2/NuRD complex. The mechanism/s that regulate DNA methylation at these enhancers are largely unknown. Here, we investigated the affect of the Lsd1-Mi2/NuRD complex on the dynamic regulatory switch that induces the local interaction of histone tails with the Dnmt3 ATRX-DNMT3-DNMT3L (ADD) domain, thus promoting DNA methylation at the enhancers of a subset of pluripotency genes. This is supported by previous structural studies showing a specific interaction between Dnmt3-ADD domain with H3K4 unmethylated histone tails that is disrupted by histone H3K4 methylation and histone acetylation. Our data suggest that Dnmt3a activity is triggered by Lsd1-Mi2/NuRD-mediated histone deacetylation and demethylation at these pluripotency gene enhancers when they are inactivated during mouse ESC differentiation. Using Dnmt3 knockout ESCs and the inhibitors of Lsd1 and p300 histone modifying enzymes during differentiation of E14Tg2A and ZHBTc4 ESCs, our study systematically reveals this mechanism and establishes that Dnmt3a is both reader and effector of the epigenetic state at these target sites. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Minimising toxicity of cadmium in plants--role of plant growth regulators.

PubMed

Asgher, Mohd; Khan, M Iqbal R; Anjum, Naser A; Khan, Nafees A

2015-03-01

A range of man-made activities promote the enrichment of world-wide agricultural soils with a myriad of chemical pollutants including cadmium (Cd). Owing to its significant toxic consequences in plants, Cd has been one of extensively studied metals. However, sustainable strategies for minimising Cd impacts in plants have been little explored. Plant growth regulators (PGRs) are known for their role in the regulation of numerous developmental processes. Among major PGRs, plant hormones (such as auxins, gibberellins, cytokinins, abscisic acid, jasmonic acid, ethylene and salicylic acid), nitric oxide (a gaseous signalling molecule), brassinosteroids (steroidal phytohormones) and polyamines (group of phytohormone-like aliphatic amine natural compounds with aliphatic nitrogen structure) have gained attention by agronomist and physiologist as a sustainable media to induce tolerance in abiotic-stressed plants. Considering recent literature, this paper: (a) overviews Cd status in soil and its toxicity in plants, (b) introduces major PGRs and overviews their signalling in Cd-exposed plants, (c) appraises mechanisms potentially involved in PGR-mediated enhanced plant tolerance to Cd and (d) highlights key aspects so far unexplored in the subject area.

FoxP2 regulates neurogenesis during embryonic cortical development.

PubMed

Tsui, David; Vessey, John P; Tomita, Hideaki; Kaplan, David R; Miller, Freda D

2013-01-02

The transcription factor FoxP2 has been associated with the development of human speech but the underlying cellular function of FoxP2 is still unclear. Here we provide evidence that FoxP2 regulates genesis of some intermediate progenitors and neurons in the mammalian cortex, one of the key centers for human speech. Specifically, knockdown of FoxP2 in embryonic cortical precursors inhibits neurogenesis, at least in part by inhibiting the transition from radial glial precursors to neurogenic intermediate progenitors. Moreover, overexpression of human, but not mouse, FoxP2 enhances the genesis of intermediate progenitors and neurons. In contrast, expression of a human FoxP2 mutant that causes vocalization deficits decreases neurogenesis, suggesting that in the murine system human FoxP2 acts as a gain-of-function protein, while a human FoxP2 mutant acts as a dominant-inhibitory protein. These results support the idea that FoxP2 regulates the transition from neural precursors to transit-amplifying progenitors and ultimately neurons, and shed light upon the molecular changes that might contribute to evolution of the mammalian cortex.

Role of Architecture in the Function and Specificity of Two Notch-Regulated Transcriptional Enhancer Modules

PubMed Central

Liu, Feng; Posakony, James W.

2012-01-01

In Drosophila melanogaster, cis-regulatory modules that are activated by the Notch cell–cell signaling pathway all contain two types of transcription factor binding sites: those for the pathway's transducing factor Suppressor of Hairless [Su(H)] and those for one or more tissue- or cell type–specific factors called “local activators.” The use of different “Su(H) plus local activator” motif combinations, or codes, is critical to ensure that only the correct subset of the broadly utilized Notch pathway's target genes are activated in each developmental context. However, much less is known about the role of enhancer “architecture”—the number, order, spacing, and orientation of its component transcription factor binding motifs—in determining the module's specificity. Here we investigate the relationship between architecture and function for two Notch-regulated enhancers with spatially distinct activities, each of which includes five high-affinity Su(H) sites. We find that the first, which is active specifically in the socket cells of external sensory organs, is largely resistant to perturbations of its architecture. By contrast, the second enhancer, active in the “non-SOP” cells of the proneural clusters from which neural precursors arise, is sensitive to even simple rearrangements of its transcription factor binding sites, responding with both loss of normal specificity and striking ectopic activity. Thus, diverse cryptic specificities can be inherent in an enhancer's particular combination of transcription factor binding motifs. We propose that for certain types of enhancer, architecture plays an essential role in determining specificity, not only by permitting factor–factor synergies necessary to generate the desired activity, but also by preventing other activator synergies that would otherwise lead to unwanted specificities. PMID:22792075

Engineering of global regulators and cell surface properties toward enhancing stress tolerance in Saccharomyces cerevisiae.

PubMed

Kuroda, Kouichi; Ueda, Mitsuyoshi

2017-12-01

Microbial cell factories are subject to various stresses, leading to the reductions of metabolic activity and bioproduction efficiency. Therefore, the development of stress-tolerant microorganisms is important for improving bio-production efficiency. Recently, modifications of cell surface properties and master regulators have been shown to be effective approaches for enhancing stress tolerance. The cell surface is an attractive target owing to its interactions with the environment and its role in transmitting environmental information. Cell surface engineering in yeast has enabled the convenient modification of cell surface properties. Displaying random peptide libraries and subsequent screening can successfully improve stress tolerance. Furthermore, master regulators including transcription factors are also promising target to be engineered because stress tolerance is determined by many cooperative factors and modification of master regulators can simultaneously affect the expression of multiple downstream genes. The key single amino acid mutations in transcription factors have been identified by analyzing tolerant yeasts that were isolated by adaptive evolution under stress conditions. This enabled the reconstruction of stress-tolerant yeast without burdening cells by introducing the identified mutations. Therefore, for the construction of stress-tolerant yeast from any strains, these two approaches are promising alternatives to conventional overexpression and deletion of stress-related genes. Copyright © 2017 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

The experience of dentists who gained enhanced skills in endodontics within a novel pilot training programme.

PubMed

Eliyas, S; Briggs, P; Gallagher, J E

2017-02-24

Objective To explore the experiences of primary care dentists following training to enhance endodontic skills and their views on the implications for the NHS.Design Qualitative study using anonymised free text questionnaires.Setting Primary care general dental services within the National Health Service (NHS) in London, United Kingdom.Subjects and methods Eight primary care dentists who completed this training were asked about factors affecting participant experience of the course, perceived impact on themselves, their organisation, their patients and barriers/facilitators to providing endodontic treatment in NHS primary care. Data were transferred verbatim to a spreadsheet and thematically analysed.Intervention 24-month part-time educational and service initiative to provide endodontics within the NHS, using a combination of training in simulation lab and treatment of patients in primary care.Results Positive impacts were identified at individual (gains in knowledge, skills, confidence, personal development), patient (more teeth saved, quality of care improved) and system levels (access, value for money). Suggested developments for future courses included more case discussions, teaching of practical skills earlier in the course and refinement of the triaging processes. Barriers to using the acquired skills in providing endodontic treatment in primary care within the NHS were perceived to be resources (remuneration, time, skills) and accountability. Facilitators included appropriately remunerated contracts, necessary equipment and time.Conclusion This novel pilot training programme in endodontics combining general practice experience with education/training, hands-on experience and a portfolio was perceived by participants as beneficial for extending skills and service innovation in primary dental care. The findings provide insight into primary dental care practitioners' experience with education/training and have implications for future educational initiatives in

Arctigenin enhances swimming endurance of sedentary rats partially by regulation of antioxidant pathways.

PubMed

Wu, Ruo-ming; Sun, Yan-yan; Zhou, Ting-ting; Zhu, Zhi-yuan; Zhuang, Jing-jing; Tang, Xuan; Chen, Jing; Hu, Li-hong; Shen, Xu

2014-10-01

Arctigenin, a phenylpropanoid dibenzylbutyrolactone lignan found in traditional Chinese herbs, has been determined to exhibit a variety of pharmacological activities, including anti-tumor, anti-inflammation, neuroprotection, and endurance enhancement. In the present study, we investigated the antioxidation and anti-fatigue effects of arctigenin in rats. Rat L6 skeletal muscle cell line was exposed to H2O2 (700 μmol/L), and ROS level was assayed using DCFH-DA as a probe. Male SD rats were injected with arctigenin (15 mg·kg(-1)·d(-1), ip) for 6 weeks, and then the weight-loaded forced swimming test (WFST) was performed to evaluate their endurance. The levels of antioxidant-related genes in L6 cells and the skeletal muscles of rats were analyzed using real-time RT-PCR and Western blotting. Incubation of L6 cells with arctigenin (1, 5, 20 μmol/L) dose-dependently decreased the H2O2-induced ROS production. WFST results demonstrated that chronic administration of arctigenin significantly enhanced the endurance of rats. Furthermore, molecular biology studies on L6 cells and skeletal muscles of the rats showed that arctigenin effectively increased the expression of the antioxidant-related genes, including superoxide dismutase (SOD), glutathione reductase (Gsr), glutathione peroxidase (GPX1), thioredoxin (Txn) and uncoupling protein 2 (UCP2), through regulation of two potential antioxidant pathways: AMPK/PGC-1α/PPARα in mitochondria and AMPK/p53/Nrf2 in the cell nucleus. Arctigenin efficiently enhances rat swimming endurance by elevation of the antioxidant capacity of the skeletal muscles, which has thereby highlighted the potential of this natural product as an antioxidant in the treatment of fatigue and related diseases.

Deferoxamine synergistically enhances iron-mediated AP-1 activation: a showcase of the interplay between extracellular-signal-regulated kinase and tyrosine phosphatase.

PubMed

Huang, Xi; Dai, Jisen; Huang, Chuanshu; Zhang, Qi; Bhanot, Opinder; Pelle, Edward

2007-10-01

Deferoxamine (DFO) is a drug widely used for iron overload treatment to reduce body iron burden. In the present study, it was shown in mouse epidermal JB6 cells that all iron compounds transiently induced extracellular signal-regulated kinases (ERK) phosphorylation, whereas DFO further enhanced ERK phosphorylation over long periods. The ERK phosphorylation by DFO treatment appears to be due to the inhibition of MAPK phosphatases (MKP) by DFO. The combined effects of iron-initiated MAPK activation and DFO-mediated MKP inhibition resulted in a synergistic enhancement on AP-1 activities. The results indicate that the interplay between MAPK and MKP is important in regulating the extent of AP-1 activation. It is known that administration of DFO in iron overload patients often results in allergic responses at the injection sites. The results suggest that this synergistic AP-1 activation might play a role in DFO-induced skin immune responses of iron overload patients.

Invention and Gain Analysis.

ERIC Educational Resources Information Center

Weber, Robert J.; Dixon, Stacey

1989-01-01

Gain analysis is applied to the invention of the sewing needle as well as different sewing implements and modes of sewing. The analysis includes a two-subject experiment. To validate the generality of gain heuristics and underlying switching processes, the invention of the assembly line is also analyzed. (TJH)

Understanding the administrative regulation on occupational health and trend in China.

PubMed

Zhou, Zhijun

2018-03-27

With the immense economic growth and social development, China has gained worldwide attention. With the quick growth of industrialization, several international professionals are gaining interest in occupational management system and in the role of the Chinese Government in protecting the worker's health. The Law on Prevention and Control of Occupational Diseases and the Work Safety Law are the two most important laws in China, which highlight the responsibilities of the employer, employee, governmental agencies, authorized occupational health service agency, and other stakeholders. The State Council comprises two departments, namely, the State Administration on Work Safety (SAWS) and the National Health and Family Planning Commission (NHFPC), which are responsible for governing the occupational health work. A series of regulations and standards have been promulgated by the Chinese Government to encourage or instruct the employers to fulfill their responsibility; however, several issues persist related to occupational health work, including administrative, technological, and sociocultural aspects. At present, the Chinese Government wants to enhance the reform in both economic and administrative structures, and the adjustments for modifying and/or improving the occupational health regulatory system are expected. Notably, the occupational health work in China must be altered for better.

Understanding the administrative regulation on occupational health and trend in China

PubMed Central

Zhou, Zhijun

2017-01-01

With the immense economic growth and social development, China has gained worldwide attention. With the quick growth of industrialization, several international professionals are gaining interest in occupational management system and in the role of the Chinese Government in protecting the worker's health. The Law on Prevention and Control of Occupational Diseases and the Work Safety Law are the two most important laws in China, which highlight the responsibilities of the employer, employee, governmental agencies, authorized occupational health service agency, and other stakeholders. The State Council comprises two departments, namely, the State Administration on Work Safety (SAWS) and the National Health and Family Planning Commission (NHFPC), which are responsible for governing the occupational health work. A series of regulations and standards have been promulgated by the Chinese Government to encourage or instruct the employers to fulfill their responsibility; however, several issues persist related to occupational health work, including administrative, technological, and sociocultural aspects. At present, the Chinese Government wants to enhance the reform in both economic and administrative structures, and the adjustments for modifying and/or improving the occupational health regulatory system are expected. Notably, the occupational health work in China must be altered for better. PMID:29311440

Comparative genomics analysis of Lactobacillus species associated with weight gain or weight protection

PubMed Central

Drissi, F; Merhej, V; Angelakis, E; El Kaoutari, A; Carrière, F; Henrissat, B; Raoult, D

2014-01-01

BACKGROUND: Some Lactobacillus species are associated with obesity and weight gain while others are associated with weight loss. Lactobacillus spp. and bifidobacteria represent a major bacterial population of the small intestine where lipids and simple carbohydrates are absorbed, particularly in the duodenum and jejunum. The objective of this study was to identify Lactobacillus spp. proteins involved in carbohydrate and lipid metabolism associated with weight modifications. METHODS: We examined a total of 13 complete genomes belonging to seven different Lactobacillus spp. previously associated with weight gain or weight protection. We combined the data obtained from the Rapid Annotation using Subsystem Technology, Batch CD-Search and Gene Ontology to classify gene function in each genome. RESULTS: We observed major differences between the two groups of genomes. Weight gain-associated Lactobacillus spp. appear to lack enzymes involved in the catabolism of fructose, defense against oxidative stress and the synthesis of dextrin, L-rhamnose and acetate. Weight protection-associated Lactobacillus spp. encoded a significant gene amount of glucose permease. Regarding lipid metabolism, thiolases were only encoded in the genome of weight gain-associated Lactobacillus spp. In addition, we identified 18 different types of bacteriocins in the studied genomes, and weight gain-associated Lactobacillus spp. encoded more bacteriocins than weight protection-associated Lactobacillus spp. CONCLUSIONS: The results of this study revealed that weight protection-associated Lactobacillus spp. have developed defense mechanisms for enhanced glycolysis and defense against oxidative stress. Weight gain-associated Lactobacillus spp. possess a limited ability to breakdown fructose or glucose and might reduce ileal brake effects. PMID:24567124

Comparative genomics analysis of Lactobacillus species associated with weight gain or weight protection.

PubMed

Drissi, F; Merhej, V; Angelakis, E; El Kaoutari, A; Carrière, F; Henrissat, B; Raoult, D

2014-02-24

Some Lactobacillus species are associated with obesity and weight gain while others are associated with weight loss. Lactobacillus spp. and bifidobacteria represent a major bacterial population of the small intestine where lipids and simple carbohydrates are absorbed, particularly in the duodenum and jejunum. The objective of this study was to identify Lactobacillus spp. proteins involved in carbohydrate and lipid metabolism associated with weight modifications. We examined a total of 13 complete genomes belonging to seven different Lactobacillus spp. previously associated with weight gain or weight protection. We combined the data obtained from the Rapid Annotation using Subsystem Technology, Batch CD-Search and Gene Ontology to classify gene function in each genome. We observed major differences between the two groups of genomes. Weight gain-associated Lactobacillus spp. appear to lack enzymes involved in the catabolism of fructose, defense against oxidative stress and the synthesis of dextrin, L-rhamnose and acetate. Weight protection-associated Lactobacillus spp. encoded a significant gene amount of glucose permease. Regarding lipid metabolism, thiolases were only encoded in the genome of weight gain-associated Lactobacillus spp. In addition, we identified 18 different types of bacteriocins in the studied genomes, and weight gain-associated Lactobacillus spp. encoded more bacteriocins than weight protection-associated Lactobacillus spp. The results of this study revealed that weight protection-associated Lactobacillus spp. have developed defense mechanisms for enhanced glycolysis and defense against oxidative stress. Weight gain-associated Lactobacillus spp. possess a limited ability to breakdown fructose or glucose and might reduce ileal brake effects.

Eucommia ulmoides Oliver Extract, Aucubin, and Geniposide Enhance Lysosomal Activity to Regulate ER Stress and Hepatic Lipid Accumulation

PubMed Central

Lee, Hwa-Young; Lee, Geum-Hwa; Lee, Mi-Rin; Kim, Hye-Kyung; Kim, Nan-young; Kim, Seung-Hyun; Lee, Yong-Chul; Kim, Hyung-Ryong; Chae, Han-Jung

2013-01-01

Eucommia ulmoides Oliver is a natural product widely used as a dietary supplement and medicinal plant. Here, we examined the potential regulatory effects of Eucommia ulmoides Oliver extracts (EUE) on hepatic dyslipidemia and its related mechanisms by in vitro and in vivo studies. EUE and its two active constituents, aucubin and geniposide, inhibited palmitate-induced endoplasmic reticulum (ER) stress, reducing hepatic lipid accumulation through secretion of apolipoprotein B and associated triglycerides and cholesterol in human HepG2 hepatocytes. To determine how EUE diminishes the ER stress response, lysosomal and proteasomal protein degradation activities were analyzed. Although proteasomal activity was not affected, lysosomal enzyme activities including V-ATPase were significantly increased by EUE as well as aucubin and geniposide in HepG2 cells. Treatment with the V-ATPase inhibitor, bafilomycin, reversed the inhibition of ER stress, secretion of apolipoprotein B, and hepatic lipid accumulation induced by EUE or its component, aucubin or geniposide. In addition, EUE was determined to regulate hepatic dyslipidemia by enhancing lysosomal activity and to regulate ER stress in rats fed a high-fat diet. Together, these results suggest that EUE and its active components enhance lysosomal activity, resulting in decreased ER stress and hepatic dyslipidemia. PMID:24349058

Children’s Engagement within the Preschool Classroom and Their Development of Self-Regulation

PubMed Central

Williford, Amanda P.; Vick Whittaker, Jessica E.; Vitiello, Virginia E.; Downer, Jason T.

2013-01-01

This study used an observational measure to examine how individual children’s engagement with teachers, peers, and tasks was associated with gains in self-regulation. A sample of 341 preschoolers was observed and direct assessments and teacher reports of self- regulation were obtained in the fall and spring of the preschool year. Research Findings Children’s positive engagement with teachers was related to gains in compliance/executive function and children’s active engagement with tasks was associated with gains in emotion regulation across the year. Engaging positively with teachers or peers was especially supportive of children’s gains in task orientation and reductions in dysregulation. Practice & Policy Results are discussed in relation to Vygotsky’s developmental theory, emphasizing that psychological processes are developed in the context of socially embedded interactions. Systematically observing how a child interacts with peers, teachers, and learning tasks in the preschool classroom holds potential to inform the creation of professional development aimed at supporting teachers in fostering individual children’s development within the early education environment. PMID:23441104

Is there evidence for a set point that regulates human body weight?

PubMed

Müller, Manfred J; Bosy-Westphal, Anja; Heymsfield, Steven B

2010-08-09

There is evidence for the idea that there is biological (active) control of body weight at a given set point. Body weight is the product of genetic effects (DNA), epigenetic effects (heritable traits that do not involve changes in DNA), and the environment. Regulation of body weight is asymmetric, being more effective in response to weight loss than to weight gain. However, regulation may be lost or camouflaged by Western diets, suggesting that the failure of biological control is due mainly to external factors. In this situation, the body's 'set point' (i.e., a constant 'body-inherent' weight regulated by a proportional feedback control system) is replaced by various 'settling points' that are influenced by energy and macronutrient intake in order for the body to achieve a zero energy balance. In a world of abundance, a prudent lifestyle and thus cognitive control are preconditions of effective biological control and a stable body weight. This idea also impacts future genetic research on body weight regulation. Searching for the genetic background of excess weight gain in a world of abundance is misleading since the possible biological control is widely overshadowed by the effect of the environment. In regard to clinical practice, dietary approaches to both weight loss and weight gain have to be reconsidered. In underweight patients (e.g., patients with anorexia nervosa), weight gain is supported by biological mechanisms that may or may not be suppressed by hyperalimentation. To overcome weight loss-induced counter-regulation in the overweight, biological signals have to be taken into account. Computational modeling of weight changes based on metabolic flux and its regulation will provide future strategies for clinical nutrition.

Enhancement of Glucose Uptake by Meso-Dihydroguaiaretic Acid through GLUT4 Up-Regulation in 3T3-L1 Adipocytes.

PubMed

Lee, Anna; Choi, Kyeong-Mi; Jung, Won-Beom; Jeong, Heejin; Kim, Ga-Yeong; Lee, Ju Hyun; Lee, Mi Kyeong; Hong, Jin Tae; Roh, Yoon-Seok; Sung, Sang-Hyun; Yoo, Hwan-Soo

2017-08-28

Type 2 diabetes is characterized by insulin resistance, which leads to increased blood glucose levels. Adipocytes are involved in the development of insulin resistance, resulting from the dysfunction of the insulin signaling pathway. In this study, we investigated whether meso -dihydroguaiaretic acid (MDGA) may modulate glucose uptake in adipocytes, and examined its mechanism of action. MDGA enhanced adipogenesis through up-regulation of peroxisome proliferator-activated receptor γ and CCAAT/enhancer-binding protein α in 3T3-L1 adipocytes partially differentiated with sub-optimal concentrations of insulin. MDGA also increased glucose uptake by stimulating expression and translocation of glucose transporter 4 (GLUT4) in adipocytes. These results suggest that MDGA may increase GLUT4 expression and its translocation by promoting insulin sensitivity, leading to enhanced glucose uptake.

Widespread Enhancer Activity from Core Promoters.

PubMed

Medina-Rivera, Alejandra; Santiago-Algarra, David; Puthier, Denis; Spicuglia, Salvatore

2018-06-01

Gene expression in higher eukaryotes is precisely regulated in time and space through the interplay between promoters and gene-distal regulatory regions, known as enhancers. The original definition of enhancers implies the ability to activate gene expression remotely, while promoters entail the capability to locally induce gene expression. Despite the conventional distinction between them, promoters and enhancers share many genomic and epigenomic features. One intriguing finding in the gene regulation field comes from the observation that many core promoter regions display enhancer activity. Recent high-throughput reporter assays along with clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-related approaches have indicated that this phenomenon is common and might have a strong impact on our global understanding of genome organisation and gene expression regulation. Copyright © 2018 Elsevier Ltd. All rights reserved.

Supplementation of oligofructose, but not sucralose, decreases high-fat diet induced body weight gain in mice independent of gustducin-mediated gut hormone release.

PubMed

Steensels, Sandra; Cools, Leen; Avau, Bert; Vancleef, Laurien; Farré, Ricard; Verbeke, Kristin; Depoortere, Inge

2017-03-01

Enteroendocrine cells sense nutrients through taste receptors similar to those on the tongue. Sweet and fatty acid taste receptors (FFAR) coupled to the gustatory G-protein, gustducin, on enteroendocrine cells play a role in gut hormone release. We studied if supplementation of artificial (sucralose) or prebiotic (oligofructose; OFS) sweeteners target gustducin-mediated signaling pathways to alter gut hormone release and reduce obesity-associated disorders. Wild-type (WT) and α-gustducin knockout (α-gust -/- ) mice were fed a high-fat diet and gavaged once daily (8 wk) with water or equisweet concentrations of sweeteners. OFS but not sucralose decreased body weight gain (-19 ± 3%, p < 0.01), fat pad mass (-55 ± 6%, p < 0.001), and insulin resistance (-39 ± 5%, p < 0.001) independent of α-gustducin. Neither sweetener improved glucose intolerance, while solely OFS improved the disturbed colonic permeability. OFS decreased (-65 ± 8%, p < 0.001) plasma glucagon-like peptide 1 (GLP-1) but not ghrelin and peptide YY (PYY) levels in WT mice. Cecal acetate and butyrate levels were reduced by OFS in both genotypes suggesting enhanced uptake of SCFAs that may target FFAR2 (upregulated expression) in adipose tissue. OFS, but not sucralose, reduced body weight gain and decreased intestinal permeability, but not glucose intolerance. Effects were not mediated by altered gut hormone levels or gustducin-mediated signaling. Artificial sweeteners do not affect gut hormone levels and are metabolically inert in mice on a high-fat diet. In contrast, prebiotic oligosaccharides (OFS) prevent body weight gain but not glucose intolerance. Alterations in sweet and short-chain fatty acid receptors (FFAR) (studied in WT and α-gust -/- mice) that regulate gut hormone levels are not mandatory for the positive effects of OFS. Enhanced uptake of SCFAs may favor interaction with FFAR2/3 on adipose tissue to induce weight loss. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Transcription regulation by distal enhancers: who's in the loop?

PubMed

Stadhouders, Ralph; van den Heuvel, Anita; Kolovos, Petros; Jorna, Ruud; Leslie, Kris; Grosveld, Frank; Soler, Eric

2012-01-01

Genome-wide chromatin profiling efforts have shown that enhancers are often located at large distances from gene promoters within the noncoding genome. Whereas enhancers can stimulate transcription initiation by communicating with promoters via chromatin looping mechanisms, we propose that enhancers may also stimulate transcription elongation by physical interactions with intronic elements. We review here recent findings derived from the study of the hematopoietic system.

Power-Smoothing Scheme of a DFIG Using the Adaptive Gain Depending on the Rotor Speed and Frequency Deviation

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

Lee, Hyewon; Hwang, Min; Muljadi, Eduard

In an electric power grid that has a high penetration level of wind, the power fluctuation of a large-scale wind power plant (WPP) caused by varying wind speeds deteriorates the system frequency regulation. This paper proposes a power-smoothing scheme of a doubly-fed induction generator (DFIG) that significantly mitigates the system frequency fluctuation while preventing over-deceleration of the rotor speed. The proposed scheme employs an additional control loop relying on the system frequency deviation that operates in combination with the maximum power point tracking control loop. To improve the power-smoothing capability while preventing over-deceleration of the rotor speed, the gain ofmore » the additional loop is modified with the rotor speed and frequency deviation. The gain is set to be high if the rotor speed and/or frequency deviation is large. In conclusion, the simulation results based on the IEEE 14-bus system clearly demonstrate that the proposed scheme significantly lessens the output power fluctuation of a WPP under various scenarios by modifying the gain with the rotor speed and frequency deviation, and thereby it can regulate the frequency deviation within a narrow range.« less

Power-Smoothing Scheme of a DFIG Using the Adaptive Gain Depending on the Rotor Speed and Frequency Deviation

DOE PAGES

Lee, Hyewon; Hwang, Min; Muljadi, Eduard; ...

2017-04-18

In an electric power grid that has a high penetration level of wind, the power fluctuation of a large-scale wind power plant (WPP) caused by varying wind speeds deteriorates the system frequency regulation. This paper proposes a power-smoothing scheme of a doubly-fed induction generator (DFIG) that significantly mitigates the system frequency fluctuation while preventing over-deceleration of the rotor speed. The proposed scheme employs an additional control loop relying on the system frequency deviation that operates in combination with the maximum power point tracking control loop. To improve the power-smoothing capability while preventing over-deceleration of the rotor speed, the gain ofmore » the additional loop is modified with the rotor speed and frequency deviation. The gain is set to be high if the rotor speed and/or frequency deviation is large. In conclusion, the simulation results based on the IEEE 14-bus system clearly demonstrate that the proposed scheme significantly lessens the output power fluctuation of a WPP under various scenarios by modifying the gain with the rotor speed and frequency deviation, and thereby it can regulate the frequency deviation within a narrow range.« less

Loop gain stabilizing with an all-digital automatic-gain-control method for high-precision fiber-optic gyroscope.

PubMed

Zheng, Yue; Zhang, Chunxi; Li, Lijing; Song, Lailiang; Chen, Wen

2016-06-10

For a fiber-optic gyroscope (FOG) using electronic dithers to suppress the dead zone, without a fixed loop gain, the deterministic compensation for the dither signals in the control loop of the FOG cannot remain accurate, resulting in the dither residuals in the FOG rotation rate output and the navigation errors in the inertial navigation system. An all-digital automatic-gain-control method for stabilizing the loop gain of the FOG is proposed. By using a perturbation square wave to measure the loop gain of the FOG and adding an automatic gain control loop in the conventional control loop of the FOG, we successfully obtain the actual loop gain and make the loop gain converge to the reference value. The experimental results show that in the case of 20% variation in the loop gain, the dither residuals are successfully eliminated and the standard deviation of the FOG sampling outputs is decreased from 2.00  deg/h to 0.62  deg/h (sampling period 2.5 ms, 10 points smoothing). With this method, the loop gain of the FOG can be stabilized over the operation temperature range and in the long-time application, which provides a solid foundation for the engineering applications of the high-precision FOG.

Tachykinin-1 in the central nervous system regulates adiposity in rodents.

PubMed

Trivedi, Chitrang; Shan, Xiaoye; Tung, Yi-Chun Loraine; Kabra, Dhiraj; Holland, Jenna; Amburgy, Sarah; Heppner, Kristy; Kirchner, Henriette; Yeo, Giles S H; Perez-Tilve, Diego

2015-05-01

Ghrelin is a circulating hormone that targets the central nervous system to regulate feeding and adiposity. The best-characterized neural system that mediates the effects of ghrelin on energy balance involves the activation of neuropeptide Y/agouti-related peptide neurons, expressed exclusively in the arcuate nucleus of the hypothalamus. However, ghrelin receptors are expressed in other neuronal populations involved in the control of energy balance. We combined laser capture microdissection of several nuclei of the central nervous system expressing the ghrelin receptor (GH secretagoge receptor) with microarray gene expression analysis to identify additional neuronal systems involved in the control of central nervous system-ghrelin action. We identified tachykinin-1 (Tac1) as a gene negatively regulated by ghrelin in the hypothalamus. Furthermore, we identified neuropeptide k as the TAC1-derived peptide with more prominent activity, inducing negative energy balance when delivered directly into the brain. Conversely, loss of Tac1 expression enhances the effectiveness of ghrelin promoting fat mass gain both in male and in female mice and increases the susceptibility to diet-induced obesity in ovariectomized mice. Taken together, our data demonstrate a role TAC1 in the control energy balance by regulating the levels of adiposity in response to ghrelin administration and to changes in the status of the gonadal function.

Gene regulation is governed by a core network in hepatocellular carcinoma.

PubMed

Gu, Zuguang; Zhang, Chenyu; Wang, Jin

2012-05-01

Hepatocellular carcinoma (HCC) is one of the most lethal cancers worldwide, and the mechanisms that lead to the disease are still relatively unclear. However, with the development of high-throughput technologies it is possible to gain a systematic view of biological systems to enhance the understanding of the roles of genes associated with HCC. Thus, analysis of the mechanism of molecule interactions in the context of gene regulatory networks can reveal specific sub-networks that lead to the development of HCC. In this study, we aimed to identify the most important gene regulations that are dysfunctional in HCC generation. Our method for constructing gene regulatory network is based on predicted target interactions, experimentally-supported interactions, and co-expression model. Regulators in the network included both transcription factors and microRNAs to provide a complete view of gene regulation. Analysis of gene regulatory network revealed that gene regulation in HCC is highly modular, in which different sets of regulators take charge of specific biological processes. We found that microRNAs mainly control biological functions related to mitochondria and oxidative reduction, while transcription factors control immune responses, extracellular activity and the cell cycle. On the higher level of gene regulation, there exists a core network that organizes regulations between different modules and maintains the robustness of the whole network. There is direct experimental evidence for most of the regulators in the core gene regulatory network relating to HCC. We infer it is the central controller of gene regulation. Finally, we explored the influence of the core gene regulatory network on biological pathways. Our analysis provides insights into the mechanism of transcriptional and post-transcriptional control in HCC. In particular, we highlight the importance of the core gene regulatory network; we propose that it is highly related to HCC and we believe further

CCAAT/Enhancer Binding Protein–α Regulates the Protease/Antiprotease Balance Required for Bronchiolar Epithelium Regeneration

PubMed Central

Sato, Atsuyasu; Xu, Yan; Whitsett, Jeffrey A.

2012-01-01

Many transcription factors that regulate lung morphogenesis during development are reactivated to mediate repairs of the injured adult lung. We hypothesized that CCAAT/enhancer binding protein–α (C/EBPα), a transcription factor critical for perinatal lung maturation, regulates genes required for the normal repair of the bronchiolar epithelium after injury. Transgenic CebpαΔ/Δ mice, in which Cebpa was conditionally deleted from Clara cells and Type II cells after birth, were used in this study. Airway injury was induced in mice by the intraperitoneal administration of naphthalene to ablate bronchiolar epithelial cells. Although the deletion of C/EBPα did not influence lung structure and function under unstressed conditions, C/EBPα was required for the normal repair of terminal bronchiolar epithelium after naphthalene injury. To identify cellular processes that are influenced by C/EBPα during repair, mRNA microarray was performed on terminal bronchiolar epithelial cells isolated by laser-capture microdissection. Normal repair of the terminal bronchiolar epithelium was highly associated with the mRNAs regulating antiprotease activities, and their induction required C/EBPα. The defective deposition of fibronectin in CebpαΔ/Δ mice was associated with increased protease activity and delayed differentiation of FoxJ1-expressing ciliated cells. The fibronectin and ciliated cells were restored by the intratracheal treatment of CebpαΔ/Δ mice with the serine protease inhibitor. In conclusion, C/EBPα regulates the expression of serine protease inhibitors that are required for the normal increase of fibronectin and the restoration of ciliated cells after injury. Treatment with serine protease inhibitor may aid in the recovery of injured bronchiolar epithelial cells, and prevent common chronic lung diseases. PMID:22652201

Effect of gonadectomy on AgRP-induced weight gain in rats.

PubMed

Goodin, Sean Z; Kiechler, Alicia R; Keichler, Alicia R; Smith, Marissa; Wendt, Donna; Strader, April D

2008-12-01

Agouti-related peptide (AgRP), the endogenous antagonist to the melanocortin 3 and 4 receptors, elicits robust hyperphagia and weight gain in rodents when administered directly into the central nervous system. The relative influence of AgRP to cause weight gain in rodents partially depends on the activity level of the melanocortin agonist-producing proopiomelanocortin neurons. Both proopiomelanocortin and AgRP neurons within the arcuate nucleus receive energy storage information from circulating peripheral signals such as leptin and insulin. Another modulator of AgRP activity includes the cell surface molecule syndecan-3. Because leptin and insulin affect food intake in a sexually dimorphic way in rodents and syndecan-3-deficient mice regulate adiposity levels through distinct physiological mechanisms, we hypothesized that AgRP-induced weight gain would also be sexually dimorphic in rats. In the present study, the behavioral and physiological effects of centrally-administered AgRP in male and female were investigated. In male rats, AgRP (1 nmol) induced 5 days (P < 0.0001) of significantly elevated feeding compared with vehicle-treated controls, while females displayed 3 days of hyperphagia (P < 0.05). However, 1 wk after the injection, both male and female rats gained the same percent body weight (6%). Interestingly, female rats exhibited a greater reduction in energy expenditure (Vo2) following AgRP compared with male rats (P < 0.05). Removal of the gonads did not alter cumulative food intake in male or female rats but did attenuate the dramatic reduction in Vo2 exhibited by females. Both intact and gonadectomized rats demonstrated significantly increased respiratory quotient supporting the anabolic action of AgRP (P < 0.01). These findings are novel in that they reveal sex-specific underlying physiology used to achieve weight gain following central AgRP in rats.

Application variables and their influence on forest herbicide efficacy and selectivity: gaining understanding and control

Treesearch

James H. Miller

1998-01-01

Available research is reviewed on the interactions of application variables, herbicides, and species. Objectives of this review are to gain insights into why variation occurs with herbicide performance, how current knowledge might be applied to enhance efficacy and consistency, and research pathways that should foster integration of application-efficacy models. A...

Design and Fabrication of High Gain Multi-element Multi-segment Quarter-sector Cylindrical Dielectric Resonator Antenna

NASA Astrophysics Data System (ADS)

Ranjan, Pinku; Gangwar, Ravi Kumar

2017-12-01

A novel design and analysis of quarter cylindrical dielectric resonator antenna (q-CDRA) with multi-element and multi-segment (MEMS) approach has been presented. The MEMS q-CDRA has been designed by splitting four identical quarters from a solid cylinder and then multi-segmentation approach has been utilized to design q-CDRA. The proposed antenna has been designed for enhancement in bandwidth as well as for high gain. For bandwidth enhancement, multi-segmentation method has been explained for the selection of dielectric constant of materials. The performance of the proposed MEMS q-CDRA has been demonstrated with design guideline of MEMS approach. To validate the antenna performance, three segments q-CDRA has been fabricated and analyzed practically. The simulated results have been in good agreement with measured one. The MEMS q-CDRA has wide impedance bandwidth (|S11|≤-10 dB) of 133.8 % with monopole-like radiation pattern. The proposed MEMS q-CDRA has been operating at TM01δ mode with the measured gain of 6.65 dBi and minimum gain of 4.5 dBi in entire operating frequency band (5.1-13.7 GHz). The proposed MEMS q-CDRA may find appropriate applications in WiMAX and WLAN band.

Chemoresistance induces enhanced adhesion and transendothelial penetration of neuroblastoma cells by down-regulating NCAM surface expression

PubMed Central

Blaheta, Roman A; Daher, Frederick H; Michaelis, Martin; Hasenberg, Christoph; Weich, Eva M; Jonas, Dietger; Kotchetkov, Rouslan; Doerr, Hans Willhelm; Cinatl, Jindrich

2006-01-01

Background Drug resistance to chemotherapy is often associated with increased malignancy in neuroblastoma (NB). One explanation for the link between resistance and malignancy might be that resistance facilitates cancer progression and invasion. To investigate this hypothesis, adhesion, transendothelial penetration and NCAM (CD56) adhesion receptor expression of drug-resistant versus drug-sensitive NB tumor cells were evaluated. Methods Acquired drug resistance was mimicked by exposing parental UKF-NB-2, UKF-NB-3 or IMR-32 tumor cells to increasing concentrations of vincristine- (VCR) or doxorubicin (DOX) to establish the resistant tumor cell sublines UKF-NB-2VCR, UKF-NB-2DOX, UKF-NB-3VCR, UKF-NB-3DOX, IMR-32VCR and IMR-32DOX. Additionally, the malignant behaviour of UKF-NB-4, which already possessed the intrinsic multidrug resistance (MDR) phenotype, was analyzed. UKF-NB-4 exposed to VCR or DOX were designated UKF-NB-4VCR or UKF-NB-4DOX. Combined phase contrast – reflection interference contrast microscopy was used to separately evaluate NB cell adhesion and penetration. NCAM was analyzed by flow cytometry, western blot and RT-PCR. Results VCR and DOX resistant tumor sublines showed enhanced adhesion and penetration capacity, compared to their drug naïve controls. Strongest effects were seen with UKF-NB-2VCR, UKF-NB-3VCR and IMR-32DOX. DOX or VCR treatment also evoked increased invasive behaviour of UKF-NB-4. The process of accelerated tumor invasion was accompanied by decreased NCAM surface and protein expression, and down-regulation of NCAM coding mRNA. Transfection of UKF-NB-4VCR cells with NCAM cDNA led to a significant receptor up-regulation, paralleled by diminished adhesion to an endothelial cell monolayer. Conclusion It is concluded that NB cells resistant to anticancer drugs acquire increased invasive capacity relative to non-resistant parental cells, and that enhanced invasion is caused by strong down-regulation of NCAM adhesion receptors. PMID

Self-administered nicotine differentially impacts body weight gain in obesity-prone and obesity-resistant rats.

PubMed

Rupprecht, Laura E; Smith, Tracy T; Donny, Eric C; Sved, Alan F

2017-07-01

Obesity and tobacco smoking represent the largest challenges to public health, but the causal relationship between nicotine and obesity is poorly understood. Nicotine suppresses body weight gain, a factor impacting smoking initiation and the failure to quit, particularly among obese smokers. The impact of nicotine on body weight regulation in obesity-prone and obesity-resistant populations consuming densely caloric diets is unknown. In the current experiment, body weight gain of adult male rats maintained on a high energy diet (31.8% kcal from fat) distributed into obesity-prone (OP), obesity-resistant (OR) and an intermediate group, which was placed on standard rodent chow (Chow). These rats were surgically implanted with intravenous catheters and allowed to self-administer nicotine (0 or 60μg/kg/infusion, a standard self-administration dose) in 1-h sessions for 20 consecutive days. Self-administered nicotine significantly suppressed body weight gain but not food intake in OP and Chow rats. Self-administered nicotine had no effect on body weight gain in OR rats. These data suggest that: 1) OR rats are also resistant to nicotine-induced suppression of body weight gain; and 2) nicotine may reduce levels of obesity in a subset of smokers prone to obesity. Copyright © 2017 Elsevier Inc. All rights reserved.

Weight gain following treatment of hyperthyroidism.

PubMed

Dale, J; Daykin, J; Holder, R; Sheppard, M C; Franklyn, J A

2001-08-01

Patients frequently express concern that treating hyperthyroidism will lead to excessive weight gain. This study aimed to determine the extent of, and risk factors for, weight gain in an unselected group of hyperthyroid patients. We investigated 162 consecutive hyperthyroid patients followed for at least 6 months. Height, weight, clinical features, biochemistry and management were recorded at each clinic visit. Documented weight gain was 5.42 +/- 0.46 kg (mean +/- SE) and increase in BMI was 8.49 +/- 0.71%, over a mean 24.2 +/- 1.6 months. Pre-existing obesity, Graves' disease causing hyperthyroidism, weight loss before presentation and length of follow-up each independently predicted weight gain. Patients treated with thionamides or radioiodine gained a similar amount of weight (thionamides, n = 87, 5.16 +/- 0.63 kg vs. radioiodine, n = 62, 4.75 +/- 0.57 kg, P = 0.645), but patients who underwent thyroidectomy (n = 13) gained more weight (10.27 +/- 2.56 kg vs. others, P = 0.007). Development of hypothyroidism (even transiently) was associated with weight gain (never hypothyroid, n = 102, 4.57 +/- 0.52 kg, transiently hypothyroid, n = 29, 5.37 +/- 0.85 kg, on T4, n = 31, 8.06 +/- 1.42 kg, P = 0.014). This difference remained after correcting for length of follow-up. In the whole cohort, weight increased by 3.95 +/- 0.40 kg at 1 year (n = 144) to 9.91 +/- 1.62 kg after 4 years (n = 27) (P = 0.008), representing a mean weight gain of 3.66 +/- 0.44 kg/year. We have demonstrated marked weight gain after treatment of hyperthyroidism. Pre-existing obesity, a diagnosis of Graves' disease and prior weight loss independently predicted weight gain and weight continued to rise with time. Patients who became hypothyroid, despite T4 replacement, gained most weight.

Post-transcriptional regulation tends to attenuate the mRNA noise and to increase the mRNA gain

NASA Astrophysics Data System (ADS)

Shi, Changhong; Wang, Shuqiang; Zhou, Tianshou; Jiang, Yiguo

2015-10-01

Post-transcriptional regulation is ubiquitous in prokaryotic and eukaryotic cells, but how it impacts gene expression remains to be fully explored. Here, we analyze a simple gene model in which we assume that mRNAs are produced in a constitutive manner but are regulated post-transcriptionally by a decapping enzyme that switches between the active state and the inactive state. We derive the analytical mRNA distribution governed by a chemical master equation, which can be well used to analyze the mechanism of how post-transcription regulation influences the mRNA expression level including the mRNA noise. We demonstrate that the mean mRNA level in the stochastic case is always higher than that in the deterministic case due to the stochastic effect of the enzyme, but the size of the increased part depends mainly on the switching rates between two enzyme states. More interesting is that we find that in contrast to transcriptional regulation, post-transcriptional regulation tends to attenuate noise in mRNA. Our results provide insight into the role of post-transcriptional regulation in controlling the transcriptional noise.

Gain and noise figure enhancement of Er+3/Yb+3 co-doped fiber/Raman hybrid amplifier

NASA Astrophysics Data System (ADS)

Mahran, O.

2016-02-01

An Er/Yb co-doped fiber/Raman hybrid amplifier (HA) is proposed and studied theoretically and analytically to improve the gain and noise figure of optical amplifiers. The calculations are performed under a uniform dopant and steady-state conditions. The initial energy transfer efficiency for Er/Yb co-doped fiber amplifier (EYDFA) is introduced, while the amplified spontaneous emission (ASE) is neglected. The glass fiber used for both Er/Yb and Raman amplifiers is phosphate. Different pump powers are used for both EYDFA and RA with 1 μW input signal power, 1 m length of Er/Yb amplifier and 25 km length of Raman amplifier (RA). The proposed model is validated for Er/Yb co-doped amplifier and Raman amplifier separately by comparing the calculating results with the experimental data. A high gain and low noise figure at 200 mW Raman pump power and 500 mW Er/Yb pump power are obtained for the proposed HA as compared with the experimental results of EYDFA, Raman amplifier and the EDFA/Raman hybrid amplifier.

Transcription through enhancers suppresses their activity in Drosophila

PubMed Central

2013-01-01

Background Enhancer elements determine the level of target gene transcription in a tissue-specific manner, providing for individual patterns of gene expression in different cells. Knowledge of the mechanisms controlling enhancer action is crucial for understanding global regulation of transcription. In particular, enhancers are often localized within transcribed regions of the genome. A number of experiments suggest that transcription can have both positive and negative effects on regulatory elements. In this study, we performed direct tests for the effect of transcription on enhancer activity. Results Using a transgenic reporter system, we investigated the relationship between the presence of pass-through transcription and the activity of Drosophila enhancers controlling the expression of the white and yellow genes. The results show that transcription from different promoters affects the activity of enhancers, counteracting their ability to activate the target genes. As expected, the presence of a transcriptional terminator between the inhibiting promoter and the affected enhancer strongly reduces the suppression. Moreover, transcription leads to dislodging of the Zeste protein that is responsible for the enhancer-dependent regulation of the white gene, suggesting a 'transcription interference’ mechanism for this regulation. Conclusions Our findings suggest a role for pass-through transcription in negative regulation of enhancer activity. PMID:24279291

Sp8 and COUP-TF1 reciprocally regulate patterning and Fgf signaling in cortical progenitors.

PubMed

Borello, Ugo; Madhavan, Mayur; Vilinsky, Ilya; Faedo, Andrea; Pierani, Alessandra; Rubenstein, John; Campbell, Kenneth

2014-06-01

To gain new insights into the transcriptional regulation of cortical development, we examined the role of the transcription factor Sp8, which is downstream of Fgf8 signaling and known to promote rostral cortical development. We have used a binary transgenic system to express Sp8 throughout the mouse telencephalon in a temporally restricted manner. Our results show that misexpression of Sp8 throughout the telencephalon, at early but not late embryonic stages, results in cortical hypoplasia, which is accompanied by increased cell death, reduced proliferation, and precocious neuronal differentiation. Misexpression of Sp8 at early developmental stages represses COUP-TF1 expression, a negative effector of Fgf signaling and a key promoter of posterior cortical identity, while ablation of Sp8 has the opposite effect. In addition, transgenic misexpression of COUP-TF1 resulted in downregulation of Sp8, indicating a reciprocal cross-regulation between these 2 transcription factors. Although Sp8 has been suggested to induce and/or maintain Fgf8 expression in the embryonic telencephalon, neither Fgf8 nor Fgf15 was upregulated using our gain-of-function approach. However, misexpression of Sp8 greatly increased the expression of Fgf target molecules, suggesting enhanced Fgf signaling. Thus, we propose that Sp8 promotes rostral and dorsomedial cortical development by repressing COUP-TF1 and promoting Fgf signaling in pallial progenitors.

Sp8 and COUP-TF1 Reciprocally Regulate Patterning and Fgf Signaling in Cortical Progenitors

PubMed Central

Borello, Ugo; Madhavan, Mayur; Vilinsky, Ilya; Faedo, Andrea; Pierani, Alessandra; Rubenstein, John; Campbell, Kenneth

2014-01-01

To gain new insights into the transcriptional regulation of cortical development, we examined the role of the transcription factor Sp8, which is downstream of Fgf8 signaling and known to promote rostral cortical development. We have used a binary transgenic system to express Sp8 throughout the mouse telencephalon in a temporally restricted manner. Our results show that misexpression of Sp8 throughout the telencephalon, at early but not late embryonic stages, results in cortical hypoplasia, which is accompanied by increased cell death, reduced proliferation, and precocious neuronal differentiation. Misexpression of Sp8 at early developmental stages represses COUP-TF1 expression, a negative effector of Fgf signaling and a key promoter of posterior cortical identity, while ablation of Sp8 has the opposite effect. In addition, transgenic misexpression of COUP-TF1 resulted in downregulation of Sp8, indicating a reciprocal cross-regulation between these 2 transcription factors. Although Sp8 has been suggested to induce and/or maintain Fgf8 expression in the embryonic telencephalon, neither Fgf8 nor Fgf15 was upregulated using our gain-of-function approach. However, misexpression of Sp8 greatly increased the expression of Fgf target molecules, suggesting enhanced Fgf signaling. Thus, we propose that Sp8 promotes rostral and dorsomedial cortical development by repressing COUP-TF1 and promoting Fgf signaling in pallial progenitors. PMID:23307639

Simplified Modeling of Steady-State and Transient Brillouin Gain in Magnetoactive Non-Centrosymmetric Semiconductors

NASA Astrophysics Data System (ADS)

Singh, M.; Aghamkar, P.; Sen, P. K.

With the aid of a hydrodynamic model of semiconductor-plasmas, a detailed analytical investigation is made to study both the steady-state and the transient Brillouin gain in magnetized non-centrosymmetric III-V semiconductors arising from the nonlinear interaction of an intense pump beam with the internally-generated acoustic wave, due to piezoelectric and electrostrictive properties of the crystal. Using the fact that the origin of coherent Brillouin scattering (CBS) lies in the third-order (Brillouin) susceptibility of the medium, we obtained an expression of the gain coefficient of backward Stokes mode in steady-state and transient regimes and studied the dependence of piezoelectricity, magnetic field and pump pulse duration on its growth rate. The threshold-pump intensity and optimum pulse duration for the onset of transient CBS are estimated. The piezoelectricity and externally-applied magnetic field substantially enhances the transient CBS gain coefficient in III-V semiconductors which can be of great use in the compression of scattered pulses.

Luminal lncRNAs Regulation by ERα-Controlled Enhancers in a Ligand-Independent Manner in Breast Cancer Cells

PubMed Central

Miano, Valentina; Rosti, Valentina; Manitta, Eleonora; Elhasnaoui, Jamal; Basile, Giulia

2018-01-01

Estrogen receptor-α (ERα) is a ligand-inducible protein which mediates estrogenic hormones signaling and defines the luminal BC phenotype. Recently, we demonstrated that even in absence of ligands ERα (apoERα) binds chromatin sites where it regulates transcription of several protein-coding and lncRNA genes. Noteworthy, apoERα-regulated lncRNAs marginally overlap estrogen-induced transcripts, thus representing a new signature of luminal BC genes. By the analysis of H3K27ac enrichment in hormone-deprived MCF-7 cells, we defined a set of Super Enhancers (SEs) occupied by apoERα, including one mapped in proximity of the DSCAM-AS1 lncRNA gene. This represents a paradigm of apoERα activity since its expression is largely unaffected by estrogenic treatment, despite the fact that E2 increases ERα binding on DSCAM-AS1 promoter. We validated the enrichment of apoERα, p300, GATA3, FoxM1 and CTCF at both DSCAM-AS1 TSS and at its associated SE by ChIP-qPCR. Furthermore, by analyzing MCF-7 ChIA-PET data and by 3C assays, we confirmed long range chromatin interaction between the SE and the DSCAM-AS1 TSS. Interestingly, CTCF and p300 binding showed an enrichment in hormone-depleted medium and in the presence of ERα, elucidating the dynamics of the estrogen-independent regulation of DSCAM-AS1 expression. The analysis of this lncRNA provides a paradigm of transcriptional regulation of a luminal specific apoERα regulated lncRNA. PMID:29462945

Optimization of control gain by operator adjustment

NASA Technical Reports Server (NTRS)

Kruse, W.; Rothbauer, G.

1973-01-01

An optimal gain was established by measuring errors at 5 discrete control gain settings in an experimental set-up consisting of a 2-dimensional, first-order pursuit tracking task performed by subjects (S's). No significant experience effect on optimum gain setting was found in the first experiment. During the second experiment, in which control gain was continuously adjustable, high experienced S's tended to reach the previously determined optimum gain quite accurately and quickly. Less experienced S's tended to select a marginally optimum gain either below or above the experimentally determined optimum depending on initial control gain setting, although mean settings of both groups were equal. This quick and simple method is recommended for selecting control gains for different control systems and forcing functions.

Application of multi-objective controller to optimal tuning of PID gains for a hydraulic turbine regulating system using adaptive grid particle swam optimization.

PubMed

Chen, Zhihuan; Yuan, Yanbin; Yuan, Xiaohui; Huang, Yuehua; Li, Xianshan; Li, Wenwu

2015-05-01

A hydraulic turbine regulating system (HTRS) is one of the most important components of hydropower plant, which plays a key role in maintaining safety, stability and economical operation of hydro-electrical installations. At present, the conventional PID controller is widely applied in the HTRS system for its practicability and robustness, and the primary problem with respect to this control law is how to optimally tune the parameters, i.e. the determination of PID controller gains for satisfactory performance. In this paper, a kind of multi-objective evolutionary algorithms, named adaptive grid particle swarm optimization (AGPSO) is applied to solve the PID gains tuning problem of the HTRS system. This newly AGPSO optimized method, which differs from a traditional one-single objective optimization method, is designed to take care of settling time and overshoot level simultaneously, in which a set of non-inferior alternatives solutions (i.e. Pareto solution) is generated. Furthermore, a fuzzy-based membership value assignment method is employed to choose the best compromise solution from the obtained Pareto set. An illustrative example associated with the best compromise solution for parameter tuning of the nonlinear HTRS system is introduced to verify the feasibility and the effectiveness of the proposed AGPSO-based optimization approach, as compared with two another prominent multi-objective algorithms, i.e. Non-dominated Sorting Genetic Algorithm II (NSGAII) and Strength Pareto Evolutionary Algorithm II (SPEAII), for the quality and diversity of obtained Pareto solutions set. Consequently, simulation results show that this AGPSO optimized approach outperforms than compared methods with higher efficiency and better quality no matter whether the HTRS system works under unload or load conditions. Copyright © 2014 ISA. Published by Elsevier Ltd. All rights reserved.

Optical antenna gain. I - Transmitting antennas

NASA Technical Reports Server (NTRS)

Klein, B. J.; Degnan, J. J.

1974-01-01

The gain of centrally obscured optical transmitting antennas is analyzed in detail. The calculations, resulting in near- and far-field antenna gain patterns, assume a circular antenna illuminated by a laser operating in the TEM-00 mode. A simple polynomial equation is derived for matching the incident source distribution to a general antenna configuration for maximum on-axis gain. An interpretation of the resultant gain curves allows a number of auxiliary design curves to be drawn that display the losses in antenna gain due to pointing errors and the cone angle of the beam in the far field as a function of antenna aperture size and its central obscuration. The results are presented in a series of graphs that allow the rapid and accurate evaluation of the antenna gain which may then be substituted into the conventional range equation.

Maintenance of gains following experiential therapies for depression.

PubMed

Ellison, Jennifer A; Greenberg, Leslie S; Goldman, Rhonda N; Angus, Lynne

2009-02-01

Follow-up data across an 18-month period are presented for 43 adults who had been randomly assigned and had responded to short-term client-centered (CC) and emotion-focused (EFT) therapies for major depression. Long-term effects of these short-term therapies were evaluated using relapse rates, number of asymptomatic or minimally symptomatic weeks, survival times across an 18-month follow-up, and group comparisons on self-report indices at 6- and 18-month follow-up among those clients who responded to the acute treatment phase. EFT treatment showed superior effects across 18 months in terms of less depressive relapse and greater number of asymptomatic or minimally symptomatic weeks, and the probability of maintaining treatment gains was significantly more likely in the EFT treatment than in the CC treatment. In addition, follow-up self-report results demonstrated significantly greater effects for EFT clients on reduction of depression and improvement of self-esteem, and there were trends in favor of EFT, in comparison with CC, on reduction of general symptom distress and interpersonal problems. Maintenance of treatment gains following an empathic relational treatment appears to be enhanced by the addition of specific experiential and gestalt-derived emotion-focused interventions. Clinical and theoretical implications of these findings are presented.

Self-Regulated and Technology-Enhanced Learning: A European Perspective

ERIC Educational Resources Information Center

Mooij, Ton; Steffens, Karl; Andrade, Maureen Snow

2014-01-01

Self-regulation of learning, learning to learn, and their potential stimulation by specific information and communication technologies (ICTs) are main topics in European policy. This issue of the European Educational Research Journal (EERJ) focuses on research to develop, integrate and evaluate self-regulation of learning and the potential and…

Arctigenin enhances swimming endurance of sedentary rats partially by regulation of antioxidant pathways

PubMed Central

Wu, Ruo-ming; Sun, Yan-yan; Zhou, Ting-ting; Zhu, Zhi-yuan; Zhuang, Jing-jing; Tang, Xuan; Chen, Jing; Hu, Li-hong; Shen, Xu

2014-01-01

Aim: Arctigenin, a phenylpropanoid dibenzylbutyrolactone lignan found in traditional Chinese herbs, has been determined to exhibit a variety of pharmacological activities, including anti-tumor, anti-inflammation, neuroprotection, and endurance enhancement. In the present study, we investigated the antioxidation and anti-fatigue effects of arctigenin in rats. Methods: Rat L6 skeletal muscle cell line was exposed to H2O2 (700 μmol/L), and ROS level was assayed using DCFH-DA as a probe. Male SD rats were injected with arctigenin (15 mg·kg−1·d−1, ip) for 6 weeks, and then the weight-loaded forced swimming test (WFST) was performed to evaluate their endurance. The levels of antioxidant-related genes in L6 cells and the skeletal muscles of rats were analyzed using real-time RT-PCR and Western blotting. Results: Incubation of L6 cells with arctigenin (1, 5, 20 μmol/L) dose-dependently decreased the H2O2-induced ROS production. WFST results demonstrated that chronic administration of arctigenin significantly enhanced the endurance of rats. Furthermore, molecular biology studies on L6 cells and skeletal muscles of the rats showed that arctigenin effectively increased the expression of the antioxidant-related genes, including superoxide dismutase (SOD), glutathione reductase (Gsr), glutathione peroxidase (GPX1), thioredoxin (Txn) and uncoupling protein 2 (UCP2), through regulation of two potential antioxidant pathways: AMPK/PGC-1α/PPARα in mitochondria and AMPK/p53/Nrf2 in the cell nucleus. Conclusion: Arctigenin efficiently enhances rat swimming endurance by elevation of the antioxidant capacity of the skeletal muscles, which has thereby highlighted the potential of this natural product as an antioxidant in the treatment of fatigue and related diseases. PMID:25152028

STATs shape the active enhancer landscape of T cell populations.

PubMed

Vahedi, Golnaz; Takahashi, Hayato; Nakayamada, Shingo; Sun, Hong-Wei; Sartorelli, Vittorio; Kanno, Yuka; O'Shea, John J

2012-11-21

Signaling pathways are intimately involved in cellular differentiation, allowing cells to respond to their environment by regulating gene expression. Although enhancers are recognized as key elements that regulate selective gene expression, the interplay between signaling pathways and actively used enhancer elements is not clear. Here, we use CD4(+) T cells as a model of differentiation, mapping the activity of cell-type-specific enhancer elements in T helper 1 (Th1) and Th2 cells. Our data establish that STAT proteins have a major impact on the activation of lineage-specific enhancers and the suppression of enhancers associated with alternative cell fates. Transcriptome analysis further supports a functional role for enhancers regulated by STATs. Importantly, expression of lineage-defining master regulators in STAT-deficient cells fails to fully recover the chromatin signature of STAT-dependent enhancers. Thus, these findings point to a critical role of STATs as environmental sensors in dynamically molding the specialized enhancer architecture of differentiating cells. Copyright © 2012 Elsevier Inc. All rights reserved.

STATs Shape the Active Enhancer Landscape of T Cell Populations

PubMed Central

Vahedi, Golnaz; Takahashi, Hayato; Nakayamada, Shingo; Sun, Hong-wei; Sartorelli, Vittorio; Kanno, Yuka; O’Shea, John J.

2012-01-01

SUMMARY Signaling pathways are intimately involved in cellular differentiation, allowing cells to respond to their environment by regulating gene expression. While enhancers are recognized as key elements that regulate selective gene expression, the interplay between signaling pathways and actively used enhancer elements is not clear. Here, we use CD4+ T cells as a model of differentiation, mapping the acquisition of cell-type-specific enhancer elements in T-helper 1 (Th1) and Th2 cells. Our data establish that STAT proteins have a major impact on the acquisition of lineage-specific enhancers and the suppression of enhancers associated with alternative cell fates. Transcriptome analysis further supports a functional role for enhancers regulated by STATs. Importantly, expression of lineage-defining master regulators in STAT-deficient cells fails to fully recover the chromatin signature of STAT-dependent enhancers. Thus, these findings point to a critical role of STATs as environmental sensors in dynamically molding the specialized enhancer architecture of differentiating cells. PMID:23178119

Epigenetic regulation of estrogen-dependent memory

PubMed Central

Fortress, Ashley M.; Frick, Karyn M.

2014-01-01

Hippocampal memory formation is highly regulated by post-translational histone modifications and DNA methylation. Accordingly, these epigenetic processes play a major role in the effects of modulatory factors, such as sex steroid hormones, on hippocampal memory. Our laboratory recently demonstrated that the ability of the potent estrogen 17β-estradiol (E2) to enhance hippocampal-dependent novel object recognition memory in ovariectomized female mice requires ERK-dependent histone H3 acetylation and DNA methylation in the dorsal hippocampus. Although these data provide valuable insight into the chromatin modifications that mediate the memory-enhancing effects of E2, epigenetic regulation of gene expression is enormously complex. Therefore, more research is needed to fully understand how E2 and other hormones employ epigenetic alterations to shape behavior. This review discusses the epigenetic alterations shown thus far to regulate hippocampal memory, briefly reviews the effects of E2 on hippocampal function, and describes in detail our work on epigenetic regulation of estrogenic memory enhancement. PMID:24878494

Enhancing Self-Regulation and Approaches to Learning in First-Year College Students: A Narrative-Based Programme Assessed in the Iberian Peninsula

ERIC Educational Resources Information Center

Rosario, Pedro; Nunez, Jose C.; Gonzalez-Pienda, Julio; Valle, Antonio; Trigo, Luisa; Guimaraes, Carina

2010-01-01

A programme to enhance first-year college students' self-regulated learning strategies is proposed and assessed in two samples, one from the University of Oviedo (Spain) and the other from the University of Minho (Portugal). Each sample was divided into two groups (experimental and control). The Spanish sample comprised 44 students in the…

Enhancing cellulase production by overexpression of xylanase regulator protein gene, xlnR, in Talaromyces cellulolyticus cellulase hyperproducing mutant strain.

PubMed

Okuda, Naoyuki; Fujii, Tatsuya; Inoue, Hiroyuki; Ishikawa, Kazuhiko; Hoshino, Tamotsu

2016-10-01

We obtained strains with the xylanase regulator gene, xlnR, overexpressed (HXlnR) and disrupted (DXlnR) derived from Talaromyces cellulolyticus strain C-1, which is a cellulase hyperproducing mutant. Filter paper degrading enzyme activity and cellobiohydrolase I gene expression was the highest in HXlnR, followed by C-1 and DXlnR. These results indicate that the enhancement of cellulase productivity was succeeded by xlnR overexpression.

Enhancement of quantum-enhanced LADAR receiver in nonideal phase-sensitive amplification

NASA Astrophysics Data System (ADS)

Zhang, Shuan; Liu, Hongjun; Huang, Nan; Wang, Zhaolu; Han, Jing

2017-07-01

The phase-sensitive amplification (PSA) with an injected squeezed vacuum field is theoretically investigated in quantum-enhanced laser detection and ranging (LADAR) receiver. The theoretical model of the amplified process is derived to investigate the quantum fluctuations in detail. A new method of mitigating the unflat gain of nonideal PSA is proposed by adjusting the squeezed angle of the squeezed vacuum field. The simulation results indicate that signal-noise ratio (SNR) of system can be efficiently improved and close to the ideal case by this method. This research will provide an important potential in the applications of quantum-enhanced LADAR receiver.

β-Catenin Up-regulates Atoh1 Expression in Neural Progenitor Cells by Interaction with an Atoh1 3′ Enhancer*

PubMed Central

Shi, Fuxin; Cheng, Yen-fu; Wang, Xiaohui L.; Edge, Albert S. B.

2010-01-01

Atoh1, a basic helix-loop-helix transcription factor, plays a critical role in the differentiation of several epithelial and neural cell types. We found that β-catenin, the key mediator of the canonical Wnt pathway, increased expression of Atoh1 in mouse neuroblastoma cells and neural progenitor cells, and baseline Atoh1 expression was decreased by siRNA directed at β-catenin. The up-regulation of Atoh1 was caused by an interaction of β-catenin with the Atoh1 enhancer that could be demonstrated by chromatin immunoprecipitation. We found that two putative Tcf-Lef sites in the 3′ enhancer of the Atoh1 gene displayed an affinity for β-catenin and were critical for the activation of Atoh1 transcription because mutation of either site decreased expression of a reporter gene downstream of the enhancer. Tcf-Lef co-activators were found in the complex that bound to these sites in the DNA together with β-catenin. Inhibition of Notch signaling, which has previously been shown to induce bHLH transcription factor expression, increased β-catenin expression in progenitor cells of the nervous system. Because this could be a mechanism for up-regulation of Atoh1 after inhibition of Notch, we tested whether siRNA to β-catenin prevented the increase in Atoh1 and found that β-catenin expression was required for increased expression of Atoh1 after Notch inhibition. PMID:19864427

Optical antenna gain. III - The effect of secondary element support struts on transmitter gain

NASA Technical Reports Server (NTRS)

Klein, B. J.; Degnan, J. J.

1976-01-01

The effect of a secondary-element spider support structure on optical antenna transmitter gain is analyzed. An expression describing the influence of the struts on the axial gain, in both the near and far fields, is derived as a function of the number of struts and their width. It is found that, for typical systems, the struts degrade the on-axis gain by less than 0.4 dB, and the first side-lobe level is not increased significantly. Contour plots have also been included to show the symmetry of the far-field distributions for three- and four-support members.

High-gain magnetized inertial fusion.

PubMed

Slutz, Stephen A; Vesey, Roger A

2012-01-13

Magnetized inertial fusion (MIF) could substantially ease the difficulty of reaching plasma conditions required for significant fusion yields, but it has been widely accepted that the gain is not sufficient for fusion energy. Numerical simulations are presented showing that high-gain MIF is possible in cylindrical liner implosions based on the MagLIF concept [S. A. Slutz et al Phys. Plasmas 17, 056303 (2010)] with the addition of a cryogenic layer of deuterium-tritium (DT). These simulations show that a burn wave propagates radially from the magnetized hot spot into the surrounding much denser cold DT given sufficient hot-spot areal density. For a drive current of 60 MA the simulated gain exceeds 100, which is more than adequate for fusion energy applications. The simulated gain exceeds 1000 for a drive current of 70 MA.

How Does Self-Regulation Affect Computer-Programming Achievement in a Blended Context?

ERIC Educational Resources Information Center

Cigdem, Harun

2015-01-01

This study focuses on learners' self-regulation which is one of the essential skills for student achievement in blended courses. Research on learners' self-regulation skills in blended learning environments has gained popularity in recent years however only a few studies investigating the correlation between self-regulation skills and student…

An ATF4-ATG5 signaling in hypothalamic POMC neurons regulates obesity.

PubMed

Xiao, Yuzhong; Deng, Yalan; Yuan, Feixiang; Xia, Tingting; Liu, Hao; Li, Zhigang; Chen, Shanghai; Liu, Zhixue; Ying, Hao; Liu, Yi; Zhai, Qiwei; Guo, Feifan

2017-06-03

ATF4 (activating transcription factor 4) is an important transcription factor that has many biological functions, while its role in hypothalamic POMC (pro-opiomelanocortin-α) neurons in the regulation of energy homeostasis has not been explored. We recently discovered that mice with an Atf4 deletion specific to POMC neurons (PAKO mice) are lean and have higher energy expenditure. Furthermore, these mice are resistant to high-fat diet (HFD)-induced obesity and obesity-related metabolic disorders. Mechanistically, we found the expression of ATG5 (autophagy-related 5) is upregulated in POMC neurons of PAKO mice, and ATF4 regulates ATG5 expression by binding directly to its promoter. Mice with Atf4 and Atg5 double knockout in POMC neurons have reduced energy expenditure and gain more fat mass compared with PAKO mice under a HFD. Finally, the effect of Atf4 knockout in POMC neurons is possibly mediated by enhanced ATG5-dependent macroautophagy/autophagy and α-melanocyte-stimulating hormone (α-MSH) production in the hypothalamus. Together, this work not only identifies a beneficial role for ATF4 in hypothalamic POMC neurons in the regulation of obesity, but also provides a new potential therapeutic target for obesity and obesity-related metabolic diseases.

Information Propagation in Developmental Enhancers

NASA Astrophysics Data System (ADS)

Jena, Siddhartha; Levine, Michael

Rather than encoding information about protein sequence, certain lengths of noncoding DNA, called enhancers, interact with protein machinery such as transcription factors to precisely regulate gene expression. Enhancers have been studied extensively in the fruit fly Drosophila melanogaster, where they regulate the expression of developmental genes that establish the blueprint of the adult fly. It has been suggested that enhancer sequences possess a specific but unknown syntax with regards to the placement and strength of transcription factor binding sites. Moreover, studies in divergent fly species have shown that compensatory evolution allows for maintenance of enhancer functionality despite considerable variation in primary DNA sequence. Here, the possible role of enhancers as signal processing modules is studied as a way of explaining these two findings. We first demonstrate how this framework can be used to explain the fine-tuned spatiotemporal dynamics of gene expression. We then explore the evolutionary pressure on enhancer sequences and the resulting emergence of enhancers that are linked by compensatory mutations. This study provides a possible mechanism for the function of multiple enhancers linked to a single gene.

Design of Silicon Photonic Crystal Waveguides for High Gain Raman Amplification Using Two Symmetric Transvers-Electric-Like Slow-Light Modes

NASA Astrophysics Data System (ADS)

Hsiao, Yi-Hua; Iwamoto, Satoshi; Arakawa, Yasuhiko

2013-04-01

We designed silicon photonic crystal (PhC) waveguides (WGs) for efficient silicon Raman amplifiers and lasers. We adopted narrow-width WGs to utilize two symmetric transvers-electric-like (TE-like) guided modes, which permit efficient external coupling for both the pump and Stokes waves. Modifying the size and shape of air holes surrounding the line-defect WG structures could tune the frequency difference between these two modes, at the Brillouin-zone edge, to match the Raman shift of silicon. Thus, small group velocities are also available both for pump and Stokes waves simultaneously, which results in a large enhancement of Raman gain. The enhancement factor of the Raman gain in the designed structure is more than 100 times that reported previously.

Helping Others Regulate Emotion Predicts Increased Regulation of One's Own Emotions and Decreased Symptoms of Depression.

PubMed

Doré, Bruce P; Morris, Robert R; Burr, Daisy A; Picard, Rosalind W; Ochsner, Kevin N

2017-05-01

Although much research considers how individuals manage their own emotions, less is known about the emotional benefits of regulating the emotions of others. We examined this topic in a 3-week study of an online platform providing training and practice in the social regulation of emotion. We found that participants who engaged more by helping others (vs. sharing and receiving support for their own problems) showed greater decreases in depression, mediated by increased use of reappraisal in daily life. Moreover, social regulation messages with more other-focused language (i.e., second-person pronouns) were (a) more likely to elicit expressions of gratitude from recipients and (b) predictive of increased use of reappraisal over time for message composers, suggesting perspective-taking enhances the benefits of practicing social regulation. These findings unpack potential mechanisms of socially oriented training in emotion regulation and suggest that by helping others regulate, we may enhance our own regulatory skills and emotional well-being.

Eupafolin enhances TRAIL-mediated apoptosis through cathepsin S-induced down-regulation of Mcl-1 expression and AMPK-mediated Bim up-regulation in renal carcinoma Caki cells.

PubMed

Han, Min Ae; Min, Kyoung-Jin; Woo, Seon Min; Seo, Bo Ram; Kwon, Taeg Kyu

2016-10-04

Eupafolin, a flavone found in Artemisia princeps, has been reported for its anti-tumor activity in several cancer cells. In this study, we examined whether eupafolin could sensitize TRAIL-mediated apoptosis in human renal carcinoma Caki cells. We found that eupafolin alone and TRAIL alone had no effect on apoptosis. However, combined treatment with eupafolin and TRAIL markedly induced apoptosis in human renal carcinoma (Caki) cells, glioma cells (U251MG), and prostate cancer cells (DU145), but not normal cells [mesangial cells (MC) and normal mouse kidney cells (TCMK-1)]. Eupafolin induced down-regulation of Mcl-1 expression at the post-translational levels in cathepsin S-dependent manner, and over-expression of Mcl-1 markedly blocked apoptosis induced by combined treatment with eupafolin and TRAIL. In addition, eupafolin increased Bim expression at the post-translational levels via AMP-activated protein kinase (AMPK)-mediated inhibition of proteasome activity. Knock-down of Bim expression by siRNA inhibited eupafolin plus TRAIL-induced apoptosis. Furthermore, combined treatment with eupafolin and TRAIL reduced tumor growth in xenograft models. Taken together, these results suggest that eupafolin enhanced TRAIL-mediated apoptosis via down-regulation of Mcl-1 and up-regulation of Bim in renal carcinoma Caki cells.

Eupafolin enhances TRAIL-mediated apoptosis through cathepsin S-induced down-regulation of Mcl-1 expression and AMPK-mediated Bim up-regulation in renal carcinoma Caki cells

PubMed Central

Woo, Seon Min; Seo, Bo Ram; Kwon, Taeg Kyu

2016-01-01

Eupafolin, a flavone found in Artemisia princeps, has been reported for its anti-tumor activity in several cancer cells. In this study, we examined whether eupafolin could sensitize TRAIL-mediated apoptosis in human renal carcinoma Caki cells. We found that eupafolin alone and TRAIL alone had no effect on apoptosis. However, combined treatment with eupafolin and TRAIL markedly induced apoptosis in human renal carcinoma (Caki) cells, glioma cells (U251MG), and prostate cancer cells (DU145), but not normal cells [mesangial cells (MC) and normal mouse kidney cells (TCMK-1)]. Eupafolin induced down-regulation of Mcl-1 expression at the post-translational levels in cathepsin S-dependent manner, and over-expression of Mcl-1 markedly blocked apoptosis induced by combined treatment with eupafolin and TRAIL. In addition, eupafolin increased Bim expression at the post-translational levels via AMP-activated protein kinase (AMPK)-mediated inhibition of proteasome activity. Knock-down of Bim expression by siRNA inhibited eupafolin plus TRAIL-induced apoptosis. Furthermore, combined treatment with eupafolin and TRAIL reduced tumor growth in xenograft models. Taken together, these results suggest that eupafolin enhanced TRAIL-mediated apoptosis via down-regulation of Mcl-1 and up-regulation of Bim in renal carcinoma Caki cells. PMID:27582546

Resonant Gain Singularities in 1D and 3D Metal/Dielectric Multilayered Nanostructures.

PubMed

Caligiuri, Vincenzo; Pezzi, Luigia; Veltri, Alessandro; De Luca, Antonio

2017-01-24

We present a detailed study on the resonant gain (RG) phenomena occurring in two nanostructures, in which the presence of dielectric singularities is used to reach a huge amplification of the emitted photons resonantly interacting with the system. The presence of gain molecules in the considered nanoresonator systems makes it possible to obtain optical features that are able to unlock several applications. Two noticeable cases have been investigated: a 1D nanoresonator based on hyperbolic metamaterials and a 3D metal/dielectric spherical multishell. The former has been designed in the framework of the effective medium theory, in order to behave as an epsilon-near-zero-and-pole metamaterial, showing extraordinary light confinement and collimation. Such a peculiarity represents the key to lead to a RG behavior, a condition in which the system is demonstrated to behave as a self-amplifying perfect lens. Very high enhancement and spectral sharpness of 1 nm of the emitted light are demonstrated by means of a transfer matrix method simulation. The latter system consists of a metal/doped-dielectric multishell. A dedicated theoretical approach has been set up to finely engineer its doubly tunable resonant nature. The RG condition has been demonstrated also in this case. Finite element method-based simulations, together with an analytical model, clarify the electric field distribution inside the multishell and suggest the opportunity to use this device as a self-enhanced loss compensated multishell, being a favorable scenario for low-threshold SPASER action. Counterintuitively, exceeding the resonant gain amount of molecules in both systems causes a significant drop in the amplitude of the resonance.

New quality regulations versus established nursing home practice: a qualitative study.

PubMed

Sandvoll, Anne Marie; Kristoffersen, Kjell; Hauge, Solveig

2012-06-07

Western governments have initiated reforms to improve the quality of care for nursing home residents. Most of these reforms encompass the use of regulations and national quality indicators. In the Norwegian context, these regulations comprise two pages of text that are easy to read and understand. They focus particularly on residents' rights to plan their day-to-day life in nursing homes. However, the research literature indicates that the implementation of the new regulations, particularly if they aim to change nursing practice, is extremely challenging. The aim of this study was to further explore and describe nursing practice to gain a deeper understanding of why it is so hard to implement the new regulations. For this qualitative study, an ethnographic design was chosen to explore and describe nursing practice. Fieldwork was conducted in two nursing homes. In total, 45 nurses and nursing aides were included in participant observation, and 10 were interviewed at the end of the field study. Findings indicate that the staff knew little about the new quality regulations, and that the quality of their work was guided by other factors rooted in their nursing practice. Further analyses revealed that the staff appeared to be committed to daily routines and also that they always seemed to know what to do. Having routines and always knowing what to do mutually strengthen and enhance each other, and together they form a powerful force that makes daily nursing care a taken-for-granted activity. New regulations are challenging to implement because nursing practices are so strongly embedded. Improving practice requires systematic and deeply rooted practical change in everyday action and thinking.

Predictors of Language Gains Among School-Age Children With Language Impairment in the Public Schools.

PubMed

Justice, Laura M; Jiang, Hui; Logan, Jessica A; Schmitt, Mary Beth

2017-06-10

This study aimed to identify child-level characteristics that predict gains in language skills for children with language impairment who were receiving therapy within the public schools. The therapy provided represented business-as-usual speech/language treatment provided by speech-language pathologists in the public schools. The sample included 272 kindergartners and first-graders with language impairment who participated in a larger study titled "Speech-Therapy Experiences in the Public Schools." Multilevel regression analyses were applied to examine the extent to which select child-level characteristics, including age, nonverbal cognition, memory, phonological awareness, vocabulary, behavior problems, and self-regulation, predicted children's language gains over an academic year. Pratt indices were computed to establish the relative importance of the predictors of interest. Phonological awareness and vocabulary skill related to greater gains in language skills, and together they accounted for nearly 70% of the explained variance, or 10% of total variance at child level. Externalizing behavior, nonverbal cognition, and age were also potentially important predictors of language gains. This study significantly advances our understanding of the characteristics of children that may contribute to their language gains while receiving therapy in the public schools. Researchers can explore how these characteristics may serve to moderate treatment outcomes, whereas clinicians can assess how these characteristics may factor into understanding treatment responses.

Active hexose correlated compound enhances tumor surveillance through regulating both innate and adaptive immune responses.

PubMed

Gao, Yunfei; Zhang, Dongqing; Sun, Buxiang; Fujii, Hajime; Kosuna, Ken-Ichi; Yin, Zhinan

2006-10-01

Active hexose correlated compound (AHCC) is a mixture of polysaccharides, amino acids, lipids and minerals derived from cocultured mycelia of several species of Basidiomycete mushrooms. AHCC has been implicated to modulate immune functions and plays a protective role against infection. However, the potential role of AHCC in tumor immune surveillance is unknown. In this study, C57BL/6 mice were orally administered AHCC or water, followed by tumor cell inoculation. We showed that compared to pure water-treated mice, AHCC treatment significantly delayed tumor development after inoculation of either melanoma cell line B16F0 or lymphoma cell line EL4. Treatment with AHCC enhanced both Ag-specific activation and proliferation of CD4(+) and CD8(+) T cells, increased the number of tumor Ag-specific CD8(+) T cells, and more importantly, increased the frequency of tumor Ag-specific IFN-gamma producing CD8(+) T cells. Interestingly, AHCC treatment also showed increased cell number of NK and gammadelta T cells, indicating the role of AHCC in activating these innate-like lymphocytes. In summary, our results demonstrate that AHCC can enhance tumor immune surveillance through regulating both innate and adaptive immune responses.

Determination of the STIS CCD Gain

NASA Astrophysics Data System (ADS)

Riley, Allyssa; Monroe, TalaWanda; Lockwood, Sean

2016-09-01

This report summarizes the analysis and absolute gain results of the STIS Cycle 23 special calibration program 14424 that was designed to measure the gain of amplifiers A, C and D at nominal gain settings of 1 and 4 e-/DN. We used the mean-variance technique and the results indicate a <3.5% change in the gain for amplifier D from when it was originally calculated pre-flight. We compared these values to previous measurements from Cycles 17 through 23. This report outlines the observations, methodology, and results of the mean-variance technique.

Measurement of Antenna Bore-Sight Gain

NASA Technical Reports Server (NTRS)

Fortinberry, Jarrod; Shumpert, Thomas

2016-01-01

The absolute or free-field gain of a simple antenna can be approximated using standard antenna theory formulae or for a more accurate prediction, numerical methods may be employed to solve for antenna parameters including gain. Both of these methods will result in relatively reasonable estimates but in practice antenna gain is usually verified and documented via measurements and calibration. In this paper, a relatively simple and low-cost, yet effective means of determining the bore-sight free-field gain of a VHF/UHF antenna is proposed by using the Brewster angle relationship.

Transgenic rescue of adipocyte glucose-dependent insulinotropic polypeptide receptor expression restores high fat diet-induced body weight gain.

PubMed

Ugleholdt, Randi; Pedersen, Jens; Bassi, Maria Rosaria; Füchtbauer, Ernst-Martin; Jørgensen, Signe Marie; Kissow, Hanne-Louise; Nytofte, Nikolaj; Poulsen, Steen Seier; Rosenkilde, Mette Marie; Seino, Yutaka; Thams, Peter; Holst, Peter Johannes; Holst, Jens Juul

2011-12-30

The glucose-dependent insulinotropic polypeptide receptor (GIPr) has been implicated in high fat diet-induced obesity and is proposed as an anti-obesity target despite an uncertainty regarding the mechanism of action. To independently investigate the contribution of the insulinotropic effects and the direct effects on adipose tissue, we generated transgenic mice with targeted expression of the human GIPr to white adipose tissue or beta-cells, respectively. These mice were then cross-bred with the GIPr knock-out strain. The central findings of the study are that mice with GIPr expression targeted to adipose tissue have a similar high fat diet -induced body weight gain as control mice, significantly greater than the weight gain in mice with a general ablation of the receptor. Surprisingly, this difference was due to an increase in total lean body mass rather than a gain in total fat mass that was similar between the groups. In contrast, glucose-dependent insulinotropic polypeptide-mediated insulin secretion does not seem to be important for regulation of body weight after high fat feeding. The study supports a role of the adipocyte GIPr in nutrient-dependent regulation of body weight and lean mass, but it does not support a direct and independent role for the adipocyte or beta-cell GIPr in promoting adipogenesis.

Mycorrhizal mediated feedbacks influence net carbon gain and nutrient uptake in Andropogon gerardii.

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

Miller, R. M.; Miller, S. P.; Jastrow, J. D.

The carbon sink strength of arbuscular mycorrhizal fungi (AMF) was investigated by comparing the growth dynamics of mycorrhizal and nonmycorrhizal Andropogon gerardii plants over a wide range of equivalent tissue phosphorus : nitrogen (P : N) ratios. Host growth, apparent photosynthesis (A{sub net}), net C gain (C{sub n}) and P and N uptake were evaluated in sequential harvests of mycorrhizal and nonmycorrhizal A. gerardii plants. Response curves were used to assess the effect of assimilate supply on the mycorrhizal symbiosis in relation to the association of C with N and P. Mycorrhizal plants had higher C{sub n} than nonmycorrhizal plantsmore » at equivalent shoot P : N ratios even though colonization did not affect plant dry mass. The higher C{sub n} in mycorrhizal plants was related to both an increase in specific leaf area and enhanced photosynthesis. The additional carbon gain associated with the mycorrhizal condition was not allocated to root biomass. The C{sub n} in the mycorrhizal plants was positively related to the proportion of active colonization in the roots. The calculated difference between C{sub n} values in mycorrhizal and nonmycorrhizal plants, C{sub diff}, appeared to correspond to the sink strength of the AMF and was not an indirect result of enhanced nutrition in mycorrhizal plants.« less

IQ Gains and the Binet Decrements.

ERIC Educational Resources Information Center

Flynn, James R.

1984-01-01

Thorndike's Stanford-Binet data suggest that from 1932 to 1971-72 preschool children enjoyed greater IQ gains than older children, possibly due to the rise of television. Additional analysis indicated that gains were either due to sampling error or totally antedated 1947. Gains of 12 IQ points were found for Americans. (Author/EGS)

Pesticide regulations and farm worker safety: the need to improve pesticide regulations in Viet Nam.

PubMed

Phung, Dung Tri; Connell, Des; Miller, Greg; Rutherford, Shannon; Chu, Cordia

2012-06-01

Agricultural pesticide use in Viet Nam has more than tripled since 1990. However, pesticide legislation and regulations have not been developed in response to this large increase in usage, as a result of which pesticides pose a serious threat to human health and the environment. This paper identifies the need to improve pesticide regulations in Viet Nam through a comparative analysis of pesticide regulations in Viet Nam and the United States of America, where the rate of acute poisoning among agricultural workers is much lower than in Viet Nam and where information pertaining to pesticide regulations is made accessible to the public. The analysis identified several measures that would help to improve Viet Nam's pesticide regulations. These include enhancing pesticide legislation, clarifying the specific roles and active involvement of both the environmental and health sectors; performing a comprehensive risk-benefit evaluation of pesticide registration and management practices; improving regulations on pesticide suspension and cancellation, transport, storage and disposal; developing import and export policies and enhancing pesticide-related occupational safety programmes.

Short-term variability in body weight predicts long-term weight gain.

PubMed

Lowe, Michael R; Feig, Emily H; Winter, Samantha R; Stice, Eric

2015-11-01

Body weight in lower animals and humans is highly stable despite a very large flux in energy intake and expenditure over time. Conversely, the existence of higher-than-average variability in weight may indicate a disruption in the mechanisms responsible for homeostatic weight regulation. In a sample chosen for weight-gain proneness, we evaluated whether weight variability over a 6-mo period predicted subsequent weight change from 6 to 24 mo. A total of 171 nonobese women were recruited to participate in this longitudinal study in which weight was measured 4 times over 24 mo. The initial 3 weights were used to calculate weight variability with the use of a root mean square error approach to assess fluctuations in weight independent of trajectory. Linear regression analysis was used to examine whether weight variability in the initial 6 mo predicted weight change 18 mo later. Greater weight variability significantly predicted amount of weight gained. This result was unchanged after control for baseline body mass index (BMI) and BMI change from baseline to 6 mo and for measures of disinhibition, restrained eating, and dieting. Elevated weight variability in young women may signal the degradation of body weight regulatory systems. In an obesogenic environment this may eventuate in accelerated weight gain, particularly in those with a genetic susceptibility toward overweight. Future research is needed to evaluate the reliability of weight variability as a predictor of future weight gain and the sources of its predictive effect. The trial on which this study is based is registered at clinicaltrials.gov as NCT00456131. © 2015 American Society for Nutrition.

The effect of betahistine, a histamine H1 receptor agonist/H3 antagonist, on olanzapine-induced weight gain in first-episode schizophrenia patients.

PubMed

Poyurovsky, Michael; Pashinian, Artashes; Levi, Aya; Weizman, Ronit; Weizman, Abraham

2005-03-01

Histamine antagonism has been implicated in antipsychotic drug-induced weight gain. Betahistine, a histamine enhancer with H1 agonistic/H3 antagonistic properties (48 mg t.i.d.), was coadministered with olanzapine (10 mg/day) in three first-episode schizophrenia patients for 6 weeks. Body weight was measured at baseline and weekly thereafter. Clinical rating scales were completed at baseline and at week 6. All participants gained weight (mean weight gain 3.1+/-0.9 kg) and a similar pattern of weight gain was observed: an increase during the first 2 weeks and no additional weight gain (two patients) or minor weight loss (one patient) from weeks 3 to 6. None gained 7% of baseline weight, which is the cut-off for clinically significant weight gain. Betahistine was safe and well tolerated and did not interfere with the antipsychotic effect of olanzapine. Our findings justify a placebo-controlled evaluation of the putative weight-attenuating effect of betahistine in olanzapine-induced weight gain.

A 16.9 dBm InP DHBT W-band power amplifier with more than 20 dB gain

NASA Astrophysics Data System (ADS)

Hongfei, Yao; Yuxiong, Cao; Danyu, Wu; Xiaoxi, Ning; Yongbo, Su; Zhi, Jin

2013-07-01

A two-stage MMIC power amplifier has been realized by use of a 1-μm InP double heterojunction bipolar transistor (DHBT). The cascode structure, low-loss matching networks, and low-parasite cell units enhance the power gain. The optimum load impedance is determined from load-pull simulation. A coplanar waveguide transmission line is adopted for its ease of fabrication. The chip size is 1.5 × 1.7 mm2 with the emitter area of 16 × 1 μm × 15 μm in the output stage. Measurements show that small signal gain is more than 20 dB over 75.5-84.5 GHz and the saturated power is 16.9 dBm @ 79 GHz with gain of 15.2 dB. The high power gain makes it very suitable for medium power amplification.

Gain-guided soliton fiber laser with high-quality rectangle spectrum for ultrafast time-stretch microscopy.

PubMed

Hu, Song; Yao, Jian; Liu, Meng; Luo, Ai-Ping; Luo, Zhi-Chao; Xu, Wen-Cheng

2016-05-16

The ultrafast time-stretch microscopy has been proposed to enhance the temporal resolution of a microscopy system. The optical source is a key component for ultrafast time-stretch microscopy system. Herein, we reported on the gain-guided soliton fiber laser with high-quality rectangle spectrum for ultrafast time-stretch microscopy. By virtue of the excellent characteristics of the gain-guided soliton, the output power and the 3-dB bandwidth of the stable mode-locked soliton could be up to 3 mW and 33.7 nm with a high-quality rectangle shape, respectively. With the proposed robust optical source, the ultrafast time-stretch microscopy with the 49.6 μm resolution and a scan rate of 11 MHz was achieved without the external optical amplification. The obtained results demonstrated that the gain-guided soliton fiber laser could be used as an alternative high-quality optical source for ultrafast time-stretch microscopy and will introduce some applications in fields such as biology, chemical, and optical sensing.

Estimating soybean genetic gain for yield in the northern United States – Influence of cropping history

USDA-ARS?s Scientific Manuscript database

Mean on-farm USA soybean yield increased at a rate of 21.3 kg per ha per year between 1924 and 2010, due to adoption of yield-enhancing genetic and agronomic technologies. To estimate annual rates of genetic yield gain in three northern USA soybean maturity groups (MG) and determine if these estimat...

Near-Infrared Laser Pumped Intersubband THz Laser Gain in InGaAs-AlAsSb-InP Quantum Wells

NASA Technical Reports Server (NTRS)

Liu, An-Sheng; Ning, Cun-Zheng

1999-01-01

We investigate the possibility of using InGaAs-AlAsSb-InP coupled quantum wells to generate THz radiation by means of intersubband optical pumping. We show that large conduction band offsets of these quantum wells make it possible to use conventional near-infrared diode lasers around 1.55 micron as pump sources. Taking into account the pump-probe coherent interaction and the optical nonlinearity for the pump field, we calculate the THz gain of the quantum well structure. We show that resonant Raman scattering enhances the THz gain at low and moderate optical pumping levels. When the pump intensity is strong, the THz gain is reduced by pump-induced population redistribution and pump-probe coherent interactions.

Differential regulation of mitochondrial pyruvate carrier genes modulates respiratory capacity and stress tolerance in yeast.

PubMed

Timón-Gómez, Alba; Proft, Markus; Pascual-Ahuir, Amparo

2013-01-01

Mpc proteins are highly conserved from yeast to humans and are necessary for the uptake of pyruvate at the inner mitochondrial membrane, which is used for leucine and valine biosynthesis and as a fuel for respiration. Our analysis of the yeast MPC gene family suggests that amino acid biosynthesis, respiration rate and oxidative stress tolerance are regulated by changes in the Mpc protein composition of the mitochondria. Mpc2 and Mpc3 are highly similar but functionally different: Mpc2 is most abundant under fermentative non stress conditions and important for amino acid biosynthesis, while Mpc3 is the most abundant family member upon salt stress or when high respiration rates are required. Accordingly, expression of the MPC3 gene is highly activated upon NaCl stress or during the transition from fermentation to respiration, both types of regulation depend on the Hog1 MAP kinase. Overexpression experiments show that gain of Mpc2 function leads to a severe respiration defect and ROS accumulation, while Mpc3 stimulates respiration and enhances tolerance to oxidative stress. Our results identify the regulated mitochondrial pyruvate uptake as an important determinant of respiration rate and stress resistance.

SIRT1 Regulates Thyroid-Stimulating Hormone Release by Enhancing PIP5Kγ Activity through Deacetylation of Specific Lysine Residues in Mammals

PubMed Central

Akieda-Asai, Sayaka; Zaima, Nobuhiro; Ikegami, Koji; Kahyo, Tomoaki; Yao, Ikuko; Hatanaka, Takahiro; Iemura, Shun-ichiro; Sugiyama, Rika; Yokozeki, Takeaki; Eishi, Yoshinobu; Koike, Morio; Ikeda, Kyoji; Chiba, Takuya; Yamaza, Haruyoshi; Shimokawa, Isao; Song, Si-Young; Matsuno, Akira; Mizutani, Akiko; Sawabe, Motoji; Chao, Moses V.; Tanaka, Masashi; Kanaho, Yasunori; Natsume, Tohru; Sugimura, Haruhiko; Date, Yukari; McBurney, Michael W.; Guarente, Leonard; Setou, Mitsutoshi

2010-01-01

Background SIRT1, a NAD-dependent deacetylase, has diverse roles in a variety of organs such as regulation of endocrine function and metabolism. However, it remains to be addressed how it regulates hormone release there. Methodology/Principal Findings Here, we report that SIRT1 is abundantly expressed in pituitary thyrotropes and regulates thyroid hormone secretion. Manipulation of SIRT1 level revealed that SIRT1 positively regulated the exocytosis of TSH-containing granules. Using LC/MS-based interactomics, phosphatidylinositol-4-phosphate 5-kinase (PIP5K)γ was identified as a SIRT1 binding partner and deacetylation substrate. SIRT1 deacetylated two specific lysine residues (K265/K268) in PIP5Kγ and enhanced PIP5Kγ enzyme activity. SIRT1-mediated TSH secretion was abolished by PIP5Kγ knockdown. SIRT1 knockdown decreased the levels of deacetylated PIP5Kγ, PI(4,5)P2, and reduced the secretion of TSH from pituitary cells. These results were also observed in SIRT1-knockout mice. Conclusions/Significance Our findings indicated that the control of TSH release by the SIRT1-PIP5Kγ pathway is important for regulating the metabolism of the whole body. PMID:20668706

The brain renin‐angiotensin system plays a crucial role in regulating body weight in diet‐induced obesity in rats

PubMed Central

Winkler, Martina; Schuchard, Johanna; Stölting, Ines; Vogt, Florian M; Barkhausen, Jörg; Thorns, Christoph; Bader, Michael

2016-01-01

Background and Purpose Reduced weight gain after treatment with AT1 receptor antagonists may involve a brain‐related mechanism. Here, we investigated the role of the brain renin‐angiotensin system on weight regulation and food behaviour, with or without additional treatment with telmisartan. Methods Transgenic rats with a brain‐specific deficiency in angiotensinogen (TGR(ASrAOGEN)) and the corresponding wild‐type, Sprague Dawley (SD) rats were fed (3 months) with a high‐calorie cafeteria diet (CD) or standard chow. SD and TGR(ASrAOGEN) rats on the CD diet were also treated with telmisartan (8 mg·kg−1·d−1, 3 months). Results Compared with SD rats, TGR(ASrAOGEN) rats (i) had lower weights during chow feeding, (ii) did not become obese during CD feeding, (iii) had normal baseline leptin plasma concentrations independent of the feeding regimen, whereas plasma leptin of SD rats was increased due to CD, (iv) showed a reduced energy intake, (v) had a higher, strain‐dependent energy expenditure, which is additionally enhanced during CD feeding, (vi) had enhanced mRNA levels of pro‐opiomelanocortin and (vii) showed improved glucose control. Weight gain and energy intake in rats fed the CD diet were markedly reduced by telmisartan in SD rats but only to a minor extent in TGR(ASrAOGEN) rats. Conclusions The brain renin‐angiotensin system affects body weight regulation, feeding behaviour and metabolic disorders. When angiotensin II levels are low in brain, rats are protected from developing diet‐induced obesity and obesity‐related metabolic impairments. We further suggest that telmisartan at least partly lowers body weight via a CNS‐driven mechanism. PMID:26892671

[Acupuncture Intervention Reduced Weight Gain Induced by Hypoglycemic Agents through Food Intake-related Targets in Central Nervous System].

PubMed

Jing, Xin-yue; Ou, Chen; Lu, Sheng-feng; Zhu, Bing-mei

2015-12-01

Clinical practice shows that thiazolidinediones (TZDs) induce weight gain in patients with type-II diabetes mellitus during treatment, which restrains its application and generalization clinically. It has been demonstrated that acupuncture therapy is useful in easing obesity in clinical trials. In the present paper, we summarize the underlying mechanism of weight gain induced by TZDs through food intake-related targets in the central nervous system and analyze the possible effects of acupuncture therapy. Acupuncture therapy is expected to reduce weight gain side effect of TZDs through 1) lowering permeability of blood brain barrier to reduce TZDs concentration in the brain, 2) upregulating the expression of hypothalamic leptin and inhibiting hypothalamic neuropiptide Y expression, and 3) down-regulating activities of peroxisome proliferator-activated receptor to reduce energy intake and fat syntheses.

Determination of the conversion gain and the accuracy of its measurement for detector elements and arrays

NASA Astrophysics Data System (ADS)

Beecken, B. P.; Fossum, E. R.

1996-07-01

Standard statistical theory is used to calculate how the accuracy of a conversion-gain measurement depends on the number of samples. During the development of a theoretical basis for this calculation, a model is developed that predicts how the noise levels from different elements of an ideal detector array are distributed. The model can also be used to determine what dependence the accuracy of measured noise has on the size of the sample. These features have been confirmed by experiment, thus enhancing the credibility of the method for calculating the uncertainty of a measured conversion gain. detector-array uniformity, charge coupled device, active pixel sensor.

TSC1 regulates the balance between effector and regulatory T cells.

PubMed

Park, Yoon; Jin, Hyung-Seung; Lopez, Justine; Elly, Chris; Kim, Gisen; Murai, Masako; Kronenberg, Mitchell; Liu, Yun-Cai

2013-12-01

Mammalian target of rapamycin (mTOR) plays a crucial role in the control of T cell fate determination; however, the precise regulatory mechanism of the mTOR pathway is not fully understood. We found that T cell-specific deletion of the gene encoding tuberous sclerosis 1 (TSC1), an upstream negative regulator of mTOR, resulted in augmented Th1 and Th17 differentiation and led to severe intestinal inflammation in a colitis model. Conditional Tsc1 deletion in Tregs impaired their suppressive activity and expression of the Treg marker Foxp3 and resulted in increased IL-17 production under inflammatory conditions. A fate-mapping study revealed that Tsc1-null Tregs that lost Foxp3 expression gained a stronger effector-like phenotype compared with Tsc1-/- Foxp3+ Tregs. Elevated IL-17 production in Tsc1-/- Treg cells was reversed by in vivo knockdown of the mTOR target S6K1. Moreover, IL-17 production was enhanced by Treg-specific double deletion of Tsc1 and Foxo3a. Collectively, these studies suggest that TSC1 acts as an important checkpoint for maintaining immune homeostasis by regulating cell fate determination.

A weight-gain-for-gestational-age z score chart for the assessment of maternal weight gain in pregnancy.

PubMed

Hutcheon, Jennifer A; Platt, Robert W; Abrams, Barbara; Himes, Katherine P; Simhan, Hyagriv N; Bodnar, Lisa M

2013-05-01

To establish the unbiased relation between maternal weight gain in pregnancy and perinatal health, a classification for maternal weight gain is needed that is uncorrelated with gestational age. The goal of this study was to create a weight-gain-for-gestational-age percentile and z score chart to describe the mean, SD, and selected percentiles of maternal weight gain throughout pregnancy in a contemporary cohort of US women. The study population was drawn from normal-weight women with uncomplicated, singleton pregnancies who delivered at the Magee-Womens Hospital in Pittsburgh, PA, 1998-2008. Analyses were based on a randomly selected subset of 648 women for whom serial prenatal weight measurements were available through medical chart record abstraction (6727 weight measurements). The pattern of maternal weight gain throughout gestation was estimated by using a random-effects regression model. The estimates were used to create a chart with the smoothed means, percentiles, and SDs of gestational weight gain for each week of pregnancy. This chart allows researchers to express total weight gain as an age-standardized z score, which can be used in epidemiologic analyses to study the association between pregnancy weight gain and adverse or physiologic pregnancy outcomes independent of gestational age.

Charge Gain, Voltage Gain, and Node Capacitance of the SAPHIRA Detector Pixel by Pixel

NASA Astrophysics Data System (ADS)

Pastrana, Izabella M.; Hall, Donald N. B.; Baker, Ian M.; Jacobson, Shane M.; Goebel, Sean B.

2018-01-01

The University of Hawai`i Institute for Astronomy has partnered with Leonardo (formerly Selex) in the development of HgCdTe linear mode avalanche photodiode (L-APD) SAPHIRA detectors. The SAPHIRA (Selex Avalanche Photodiode High-speed Infra-Red Array) is ideally suited for photon-starved astronomical observations, particularly near infrared (NIR) adaptive optics (AO) wave-front sensing. I have measured the stability, and linearity with current, of a 1.7-um (10% spectral bandpass) infrared light emitting diode (IR LED) used to illuminate the SAPHIRA and have then utilized this source to determine the charge gain (in e-/ADU), voltage gain (in uV/ADU), and node capacitance (in fF) for each pixel of the 320x256@24um SAPHIRA. These have previously only been averages over some sub-array. Determined from the ratio of the temporal averaged signal level to variance under constant 1.7-um LED illumination, I present the charge gain pixel-by-pixel in a 64x64 sub-array at the center of the active area of the SAPHIRA (analyzed separately as four 32x32 sub-arrays) to be about 1.6 e-/ADU (σ=0.5 e-/ADU). Additionally, the standard technique of varying the pixel reset voltage (PRV) in 10 mV increments and recording output frames for the same 64x64 subarray found the voltage gain per pixel to be about 11.7 uV/ADU (σ=0.2 uV/ADU). Finally, node capacitance was found to be approximately 23 fF (σ=6 fF) utilizing the aforementioned charge and voltage gain measurements. I further discuss the linearity measurements of the 1.7-um LED used in the charge gain characterization procedure.

Epigenetic regulation of estrogen-dependent memory.

PubMed

Fortress, Ashley M; Frick, Karyn M

2014-10-01

Hippocampal memory formation is highly regulated by post-translational histone modifications and DNA methylation. Accordingly, these epigenetic processes play a major role in the effects of modulatory factors, such as sex steroid hormones, on hippocampal memory. Our laboratory recently demonstrated that the ability of the potent estrogen 17β-estradiol (E2) to enhance hippocampal-dependent novel object recognition memory in ovariectomized female mice requires ERK-dependent histone H3 acetylation and DNA methylation in the dorsal hippocampus. Although these data provide valuable insight into the chromatin modifications that mediate the memory-enhancing effects of E2, epigenetic regulation of gene expression is enormously complex. Therefore, more research is needed to fully understand how E2 and other hormones employ epigenetic alterations to shape behavior. This review discusses the epigenetic alterations shown thus far to regulate hippocampal memory, briefly reviews the effects of E2 on hippocampal function, and describes in detail our work on epigenetic regulation of estrogenic memory enhancement. Copyright © 2014 Elsevier Inc. All rights reserved.

Effects of Self-Regulated Vocabulary Learning Process on Self-Efficacy

ERIC Educational Resources Information Center

Mizumoto, Atsushi

2013-01-01

Researchers, especially in the field of educational psychology, have argued that self-efficacy plays an important role in self-regulated learning. As such, teaching of self-regulated learning often focuses on enhancing self-efficacy. However, few studies have examined how the process of self-regulated learning might lead to the enhancement of…

Effect of intermittent kangaroo mother care on weight gain of low birth weight neonates with delayed weight gain.

PubMed

Samra, Nashwa M; Taweel, Amal El; Cadwell, Karin

2013-01-01

To evaluate intermittent Kangaroo Mother Care (KMC) with additional opportunities to breastfeed on weight gain of low birth weight (LBW) neonates with delayed weight gain. 40 LBW neonates were followed to see whether KMC with additional opportunities to breastfeed improved weight gain. In the KMC group, the mean age of regaining birth weight was significantly less (15.68 vs. 24.56 days) and the average daily weight gain was significantly higher (22.09 vs. 10.39 g, p < .001) than controls. KMC with additional opportunities to breastfeed was found to be an effective intervention for LBWs with delayed weight gain and should be considered to be an effective strategy.

6-Shogaol enhances renal carcinoma Caki cells to TRAIL-induced apoptosis through reactive oxygen species-mediated cytochrome c release and down-regulation of c-FLIP(L) expression.

PubMed

Han, Min Ae; Woo, Seon Min; Min, Kyoung-jin; Kim, Shin; Park, Jong-Wook; Kim, Dong Eun; Kim, Sang Hyun; Choi, Yung Hyun; Kwon, Taeg Kyu

2015-02-25

6-Shogaol, a potent bioactive compound in ginger (Zingiber officinale Roscoe), has been reported for anti-inflammatory and anti-cancer activity. In this study, we investigated the effect of 6-shogaol to enhance tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis. The combined treatment with 6-shogaol and TRAIL markedly induces apoptosis in various cancer cells (renal carcinoma Caki cells, breast carcinoma MDA-MB-231 cells and glioma U118MG cells), but not in normal mesangial cells and normal mouse kidney cells. 6-Shogaol reduced the mitochondrial membrane potential (MMP) and released cytochrome c from mitochondria to cytosol via Bax activation. Furthermore, we found that 6-shogaol induced down-regulation of c-FLIP(L) expression at the post-translational levels and the overexpression of c-FLIP(L) markedly inhibited 6-shogaol plus TRAIL-induced apoptosis. Moreover, 6-shogaol increased reactive oxygen species (ROS) production in Caki cells. Pretreatment with ROS scavengers attenuated 6-shogaol plus TRAIL-induced apoptosis through inhibition of MMP reduction and down-regulation of c-FLIP(L) expression. In addition, 6-gingerol, another phenolic alkanone isolated from ginger, did not enhance TRAIL-induced apoptosis and down-regulate c-FLIP(L) expression. Taken together, our results demonstrated that 6-shogaol enhances TRAIL-mediated apoptosis in renal carcinoma Caki cells via ROS-mediated cytochrome c release and down-regulation of c-FLIP(L) expression. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

O-Linked N-Acetylglucosamine Cycling Regulates Mitotic Spindle Organization*

PubMed Central

Tan, Ee Phie; Caro, Sarah; Potnis, Anish; Lanza, Christopher; Slawson, Chad

2013-01-01

Any defects in the correct formation of the mitotic spindle will lead to chromosomal segregation errors, mitotic arrest, or aneuploidy. We demonstrate that O-linked N-acetylglucosamine (O-GlcNAc), a post-translational modification of serine and threonine residues in nuclear and cytoplasmic proteins, regulates spindle function. In O-GlcNAc transferase or O-GlcNAcase gain of function cells, the mitotic spindle is incorrectly assembled. Chromosome condensation and centrosome assembly is impaired in these cells. The disruption in spindle architecture is due to a reduction in histone H3 phosphorylation by Aurora kinase B. However, gain of function cells treated with the O-GlcNAcase inhibitor Thiamet-G restored the assembly of the spindle and partially rescued histone phosphorylation. Together, these data suggest that the coordinated addition and removal of O-GlcNAc, termed O-GlcNAc cycling, regulates mitotic spindle organization and provides a potential new perspective on how O-GlcNAc regulates cellular events. PMID:23946484

Sideband instability analysis based on a one-dimensional high-gain free electron laser model

DOE PAGES

Tsai, Cheng-Ying; Wu, Juhao; Yang, Chuan; ...

2017-12-18

When an untapered high-gain free electron laser (FEL) reaches saturation, the exponential growth ceases and the radiation power starts to oscillate about an equilibrium. The FEL radiation power or efficiency can be increased by undulator tapering. For a high-gain tapered FEL, although the power is enhanced after the first saturation, it is known that there is a so-called second saturation where the FEL power growth stops even with a tapered undulator system. The sideband instability is one of the primary reasons leading to this second saturation. In this paper, we provide a quantitative analysis on how the gradient of undulatormore » tapering can mitigate the sideband growth. The study is carried out semianalytically and compared with one-dimensional numerical simulations. The physical parameters are taken from Linac Coherent Light Source-like electron bunch and undulator systems. The sideband field gain and the evolution of the radiation spectra for different gradients of undulator tapering are examined. It is found that a strong undulator tapering (~10 % ) provides effective suppression of the sideband instability in the postsaturation regime.« less

Sideband instability analysis based on a one-dimensional high-gain free electron laser model

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

Tsai, Cheng-Ying; Wu, Juhao; Yang, Chuan

When an untapered high-gain free electron laser (FEL) reaches saturation, the exponential growth ceases and the radiation power starts to oscillate about an equilibrium. The FEL radiation power or efficiency can be increased by undulator tapering. For a high-gain tapered FEL, although the power is enhanced after the first saturation, it is known that there is a so-called second saturation where the FEL power growth stops even with a tapered undulator system. The sideband instability is one of the primary reasons leading to this second saturation. In this paper, we provide a quantitative analysis on how the gradient of undulatormore » tapering can mitigate the sideband growth. The study is carried out semianalytically and compared with one-dimensional numerical simulations. The physical parameters are taken from Linac Coherent Light Source-like electron bunch and undulator systems. The sideband field gain and the evolution of the radiation spectra for different gradients of undulator tapering are examined. It is found that a strong undulator tapering (~10 % ) provides effective suppression of the sideband instability in the postsaturation regime.« less

Estimation of sensing characteristics for refractory nitrides based gain assisted core-shell plasmonic nanoparticles

NASA Astrophysics Data System (ADS)

Shishodia, Manmohan Singh; Pathania, Pankaj

2018-04-01

Refractory transition metal nitrides such as zirconium nitride (ZrN), hafnium nitride (HfN) and titanium nitride (TiN) have emerged as viable alternatives to coinage metals based plasmonic materials, e.g., gold (Au) and silver (Ag). The present work assesses the suitability of gain assisted ZrN-, HfN- and TiN-based conventional core-shell nanoparticles (CCSNPs) and multilayered core-shell nanoparticles (MCSNPs) for refractive index sensing. We report that the optical gain incorporation in the dielectric layer leads to multifold enhancement of the scattering efficiency (Qsca), substantial reduction of the spectral full width at half maximum, and a higher figure of merit (FOM). In comparison with CCSNPs, the MCSNP system exhibits superior sensing characteristics such as higher FOM, ˜ 45% reduction in the critical optical gain, response shift towards the biological window, and higher degree of tunability. Inherent biocompatibility, growth compatibility, chemical stability and flexible spectral tuning of refractory nitrides augmented by superior sensing properties in the present work may pave the way for refractory nitrides based low cost sensing.

Sideband instability analysis based on a one-dimensional high-gain free electron laser model

NASA Astrophysics Data System (ADS)

Tsai, Cheng-Ying; Wu, Juhao; Yang, Chuan; Yoon, Moohyun; Zhou, Guanqun

2017-12-01

When an untapered high-gain free electron laser (FEL) reaches saturation, the exponential growth ceases and the radiation power starts to oscillate about an equilibrium. The FEL radiation power or efficiency can be increased by undulator tapering. For a high-gain tapered FEL, although the power is enhanced after the first saturation, it is known that there is a so-called second saturation where the FEL power growth stops even with a tapered undulator system. The sideband instability is one of the primary reasons leading to this second saturation. In this paper, we provide a quantitative analysis on how the gradient of undulator tapering can mitigate the sideband growth. The study is carried out semianalytically and compared with one-dimensional numerical simulations. The physical parameters are taken from Linac Coherent Light Source-like electron bunch and undulator systems. The sideband field gain and the evolution of the radiation spectra for different gradients of undulator tapering are examined. It is found that a strong undulator tapering (˜10 %) provides effective suppression of the sideband instability in the postsaturation regime.

Do phosphoinositides regulate membrane water permeability of tobacco protoplasts by enhancing the aquaporin pathway?

PubMed

Ma, Xiaohong; Shatil-Cohen, Arava; Ben-Dor, Shifra; Wigoda, Noa; Perera, Imara Y; Im, Yang Ju; Diminshtein, Sofia; Yu, Ling; Boss, Wendy F; Moshelion, Menachem; Moran, Nava

2015-03-01

Enhancing the membrane content of PtdInsP 2 , the already-recognized protein-regulating lipid, increased the osmotic water permeability of tobacco protoplasts, apparently by increasing the abundance of active aquaporins in their membranes. While phosphoinositides are implicated in cell volume changes and are known to regulate some ion channels, their modulation of aquaporins activity has not yet been reported for any organism. To examine this, we compared the osmotic water permeability (P f) of protoplasts isolated from tobacco (Nicotiana tabacum) cultured cells (NT1) with different (genetically lowered or elevated relative to controls) levels of inositol trisphosphate (InsP3) and phosphatidyl inositol [4,5] bisphosphate (PtdInsP2). To achieve this, the cells were transformed with, respectively, the human InsP3 5-phosphatase ('Ptase cells') or human phosphatidylinositol (4) phosphate 5-kinase ('PIPK cells'). The mean P f of the PIPK cells was several-fold higher relative to that of controls and Ptase cells. Three results favor aquaporins over the membrane matrix as underlying this excessive P f: (1) transient expression of the maize aquaporin ZmPIP2;4 in the PIPK cells increased P f by 12-30 μm s(-1), while in the controls only by 3-4 μm s(-1). (2) Cytosol acidification-known to inhibit aquaporins-lowered the P f in the PIPK cells down to control levels. (3) The transcript of at least one aquaporin was elevated in the PIPK cells. Together, the three results demonstrate the differences between the PIPK cells and their controls, and suggest a hitherto unobserved regulation of aquaporins by phosphoinositides, which could occur through direct interaction or indirect phosphoinositides-dependent cellular effects.

Comparison of Video Head Impulse Test (vHIT) Gains Between Two Commercially Available Devices and by Different Gain Analytical Methods.

PubMed

Lee, Sang Hun; Yoo, Myung Hoon; Park, Jun Woo; Kang, Byung Chul; Yang, Chan Joo; Kang, Woo Suk; Ahn, Joong Ho; Chung, Jong Woo; Park, Hong Ju

2018-06-01

To evaluate whether video head impulse test (vHIT) gains are dependent on the measuring device and method of analysis. Prospective study. vHIT was performed in 25 healthy subjects using two devices simultaneously. vHIT gains were compared between these instruments and using five different methods of comparing position and velocity gains during head movement intervals. The two devices produced different vHIT gain results with the same method of analysis. There were also significant differences in the vHIT gains measured using different analytical methods. The gain analytic method that compares the areas under the velocity curve (AUC) of the head and eye movements during head movements showed lower vHIT gains than a method that compared the peak velocities of the head and eye movements. The former method produced the vHIT gain with the smallest standard deviation among the five procedures tested in this study. vHIT gains differ in normal subjects depending on the device and method of analysis used, suggesting that it is advisable for each device to have its own normal values. Gain calculations that compare the AUC of the head and eye movements during the head movements show the smallest variance.

Can LENR Energy Gains Exceed 1000?

NASA Astrophysics Data System (ADS)

Nagel, David J.

2011-03-01

Energy gain is defined as the energy realized from reactions divided by the energy required to produce those reactions. Low Energy Nuclear Reactions (LENR) have already been measured to significantly exceed the energy gain of 10 projected from ITER,possibly 15 years from now. Electrochemical experiments using the Pd-D system have shown energy gains exceeding 10. Gas phase experiments with the Ni-H system were reported to yield energy gains of over 100. Neither of these reports has been adequately verified or reproduced. However, the question in the title still deserves consideration. If, as thought by many, it is possible to trigger nuclear reactions that yield MeV energies with chemical energies of the order of eV, then the most optimistic expectation is that LENR gains could approach one million. Hence, the very tentative answer to the question above is yes. However, if LENR could be initiated with some energy cost, and then continue to ``burn,'' very high energy gains might be realized. Consider a match and a pile of dry logs. The phenomenon termed ``heat after death'' will be examined to see if it might be the initial evidence for nuclear ``burning.''

Controlling gain one photon at a time

PubMed Central

Schwartz, Gregory W; Rieke, Fred

2013-01-01

Adaptation is a salient property of sensory processing. All adaptational or gain control mechanisms face the challenge of obtaining a reliable estimate of the property of the input to be adapted to and obtaining this estimate sufficiently rapidly to be useful. Here, we explore how the primate retina balances the need to change gain rapidly and reliably when photons arrive rarely at individual rod photoreceptors. We find that the weakest backgrounds that decrease the gain of the retinal output signals are similar to those that increase human behavioral threshold, and identify a novel site of gain control in the retinal circuitry. Thus, surprisingly, the gain of retinal signals begins to decrease essentially as soon as background lights are detectable; under these conditions, gain control does not rely on a highly averaged estimate of the photon count, but instead signals from individual photon absorptions trigger changes in gain. DOI: http://dx.doi.org/10.7554/eLife.00467.001 PMID:23682314

Detection of gain enhancement in laser-induced fluorescence of rhodamine B lasing dye by silicon dioxide nanostructures-coated cavity

NASA Astrophysics Data System (ADS)

Al-Tameemi, Mohammed N. A.

2018-03-01

In this work, nanostructured silicon dioxide films are deposited by closed-field unbalanced direct-current (DC) reactive magnetron sputtering technique on two sides of quartz cells containing rhodamine B dye dissolved in ethanol with 10‒5 M concentration as a random gain medium. The preparation conditions are optimized to prepare highly pure SiO2 nanostructures with a minimum particle size of about 20 nm. The effect of SiO2 films as external cavity for the random gain medium is determined by the laser-induced fluorescence of this medium, and an increase of about 200% in intensity is observed after the deposition of nanostructured SiO2 thin films on two sides of the dye cell.

Aging yeast gain a competitive advantage on non-optimal carbon sources.

PubMed

Frenk, Stephen; Pizza, Grazia; Walker, Rachael V; Houseley, Jonathan

2017-06-01

Animals, plants and fungi undergo an aging process with remarkable physiological and molecular similarities, suggesting that aging has long been a fact of life for eukaryotes and one to which our unicellular ancestors were subject. Key biochemical pathways that impact longevity evolved prior to multicellularity, and the interactions between these pathways and the aging process therefore emerged in ancient single-celled eukaryotes. Nevertheless, we do not fully understand how aging impacts the fitness of unicellular organisms, and whether such cells gain a benefit from modulating rather than simply suppressing the aging process. We hypothesized that age-related loss of fitness in single-celled eukaryotes may be counterbalanced, partly or wholly, by a transition from a specialist to a generalist life-history strategy that enhances adaptability to other environments. We tested this hypothesis in budding yeast using competition assays and found that while young cells are more successful in glucose, highly aged cells outcompete young cells on other carbon sources such as galactose. This occurs because aged yeast divide faster than young cells in galactose, reversing the normal association between age and fitness. The impact of aging on single-celled organisms is therefore complex and may be regulated in ways that anticipate changing nutrient availability. We propose that pathways connecting nutrient availability with aging arose in unicellular eukaryotes to capitalize on age-linked diversity in growth strategy and that individual cells in higher eukaryotes may similarly diversify during aging to the detriment of the organism as a whole. © 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Effect of Intermittent Kangaroo Mother Care on Weight Gain of Low Birth Weight Neonates With Delayed Weight Gain

PubMed Central

Samra, Nashwa M.; Taweel, Amal El; Cadwell, Karin

2013-01-01

Objective: To evaluate intermittent Kangaroo Mother Care (KMC) with additional opportunities to breastfeed on weight gain of low birth weight (LBW) neonates with delayed weight gain. Methods: 40 LBW neonates were followed to see whether KMC with additional opportunities to breastfeed improved weight gain. Results: In the KMC group, the mean age of regaining birth weight was significantly less (15.68 vs. 24.56 days) and the average daily weight gain was significantly higher (22.09 vs. 10.39 g, p < .001) than controls. Conclusion: KMC with additional opportunities to breastfeed was found to be an effective intervention for LBWs with delayed weight gain and should be considered to be an effective strategy. PMID:24868132

Dissecting mitochondrial apoptosis pathways by gain-of-function cell culture screens.

PubMed

Grimm, Stefan

2013-05-01

While more primitive organism such as Caenorhabditis elegans and Drosophila melanogaster feature a limited, and by now probably mostly known, array of basic cell death factors, the mammalian cell is replete with additional regulators of the cell's demise. This abundance of apoptosis mediators has made it imperative to set up a systematic inventory of mammalian cell death genes. Genetic screens in this biological system have recently uncovered the rich diversity of cell death signalling and have in particular highlighted mitochondria as an organelle loaded with apoptosis regulators. Many of the screens that have addressed this utilised the novel technique of RNA interference but some also looked at gain-of-functions with transfected cDNAs. Here we give an overview of the rationale for the latter approach, present the genes discovered by this strategy and in particular describe the involvement of mitochondria and their signalling pathways defined by those genes. Copyright © 2012 Elsevier B.V. and Mitochondria Research Society. All rights reserved.

Zyflamend Sensitizes Tumor Cells to TRAIL-Induced Apoptosis Through Up-Regulation of Death Receptors and Down-Regulation of Survival Proteins: Role of ROS-Dependent CCAAT/Enhancer-Binding Protein-Homologous Protein Pathway

PubMed Central

Kim, Ji Hye; Park, Byoungduck; Gupta, Subash C.; Kannappan, Ramaswamy; Sung, Bokyung

2012-01-01

Abstract Aim: TNF (tumor necrosis factor)-related apoptosis-inducing ligand (TRAIL), is a selective killer of tumor cells, although its potential is limited by the development of resistance. In this article, we investigated whether the polyherbal preparation Zyflamend® can sensitize tumor cells to TRAIL. Results: We found that Zyflamend potentiated TRAIL-induced apoptosis in human cancer cells. Zyflamend manifested its effects through several mechanisms. First, it down-regulated the expression of cell survival proteins known to be linked to resistance to TRAIL. Second, Zyflamend up-regulated the expression of pro-apoptotic protein, Bax. Third, Zyflamend up-regulated the expression of death receptors (DRs) for TRAIL. Up-regulation of DRs was critical as gene-silencing of these receptors significantly reduced the effect of Zyflamend on TRAIL-induced apoptosis. The up-regulation of DRs was dependent on CCAAT/enhancer-binding protein-homologous protein (CHOP), as Zyflamend induced CHOP, its gene-silencing abolished the induction of receptors, and mutation of the CHOP binding site on DR5 promoter abolished Zyflamend-mediated DR5 transactivation. Zyflamend mediated its effects through reactive oxygen species (ROS), as ROS quenching reduced its effect. Further, Zyflamend induced DR5 and CHOP and down-regulated the expression of cell survival proteins in nude mice bearing human pancreatic cancer cells. Innovation: Zyflamend can sensitize tumor cells to TRAIL through modulation of multiple cell signaling mechanisms that are linked to ROS. Conclusion: Zyflamend potentiates TRAIL-induced apoptosis through the ROS-CHOP-mediated up-regulation of DRs, increase in pro-apoptotic protein and down-regulation of cell survival proteins. Antioxid. Redox Signal. 16, 413–427. PMID:22004570

Pesticide regulations and farm worker safety: the need to improve pesticide regulations in Viet Nam

PubMed Central

Connell, Des; Miller, Greg; Rutherford, Shannon; Chu, Cordia

2012-01-01

Abstract Agricultural pesticide use in Viet Nam has more than tripled since 1990. However, pesticide legislation and regulations have not been developed in response to this large increase in usage, as a result of which pesticides pose a serious threat to human health and the environment. This paper identifies the need to improve pesticide regulations in Viet Nam through a comparative analysis of pesticide regulations in Viet Nam and the United States of America, where the rate of acute poisoning among agricultural workers is much lower than in Viet Nam and where information pertaining to pesticide regulations is made accessible to the public. The analysis identified several measures that would help to improve Viet Nam’s pesticide regulations. These include enhancing pesticide legislation, clarifying the specific roles and active involvement of both the environmental and health sectors; performing a comprehensive risk–benefit evaluation of pesticide registration and management practices; improving regulations on pesticide suspension and cancellation, transport, storage and disposal; developing import and export policies and enhancing pesticide-related occupational safety programmes. PMID:22690037

Antipsychotic-induced insulin resistance and postprandial hormonal dysregulation independent of weight gain or psychiatric disease.

PubMed

Teff, Karen L; Rickels, Michael R; Grudziak, Joanna; Fuller, Carissa; Nguyen, Huong-Lan; Rickels, Karl

2013-09-01

Atypical antipsychotic (AAP) medications that have revolutionized the treatment of mental illness have become stigmatized by metabolic side effects, including obesity and diabetes. It remains controversial whether the defects are treatment induced or disease related. Although the mechanisms underlying these metabolic defects are not understood, it is assumed that the initiating pathophysiology is weight gain, secondary to centrally mediated increases in appetite. To determine if the AAPs have detrimental metabolic effects independent of weight gain or psychiatric disease, we administered olanzapine, aripiprazole, or placebo for 9 days to healthy subjects (n = 10, each group) under controlled in-patient conditions while maintaining activity levels. Prior to and after the interventions, we conducted a meal challenge and a euglycemic-hyperinsulinemic clamp to evaluate insulin sensitivity and glucose disposal. We found that olanzapine, an AAP highly associated with weight gain, causes significant elevations in postprandial insulin, glucagon-like peptide 1 (GLP-1), and glucagon coincident with insulin resistance compared with placebo. Aripiprazole, an AAP considered metabolically sparing, induces insulin resistance but has no effect on postprandial hormones. Importantly, the metabolic changes occur in the absence of weight gain, increases in food intake and hunger, or psychiatric disease, suggesting that AAPs exert direct effects on tissues independent of mechanisms regulating eating behavior.

Modification of saccadic gain by reinforcement

PubMed Central

Paeye, Céline; Wallman, Josh

2011-01-01

Control of saccadic gain is often viewed as a simple compensatory process in which gain is adjusted over many trials by the postsaccadic retinal error, thereby maintaining saccadic accuracy. Here, we propose that gain might also be changed by a reinforcement process not requiring a visual error. To test this hypothesis, we used experimental paradigms in which retinal error was removed by extinguishing the target at the start of each saccade and either an auditory tone or the vision of the target on the fovea was provided as reinforcement after those saccades that met an amplitude criterion. These reinforcement procedures caused a progressive change in saccade amplitude in nearly all subjects, although the rate of adaptation differed greatly among subjects. When we reversed the contingencies and reinforced those saccades landing closer to the original target location, saccade gain changed back toward normal gain in most subjects. When subjects had saccades adapted first by reinforcement and a week later by conventional intrasaccadic step adaptation, both paradigms yielded similar degrees of gain changes and similar transfer to new amplitudes and to new starting positions of the target step as well as comparable rates of recovery. We interpret these changes in saccadic gain in the absence of postsaccadic retinal error as showing that saccade adaptation is not controlled by a single error signal. More generally, our findings suggest that normal saccade adaptation might involve general learning mechanisms rather than only specialized mechanisms for motor calibration. PMID:21525366

MicroRNA-431 regulates axon regeneration in mature sensory neurons by targeting the Wnt antagonist Kremen1

PubMed Central

Wu, Di; Murashov, Alexander K.

2013-01-01

MicroRNAs (miRNAs) are small, non-coding RNAs that function as key post-transcriptional regulators in neural development, brain function, and neurological diseases. Growing evidence indicates that miRNAs are also important mediators of nerve regeneration, however, the affected signaling mechanisms are not clearly understood. In the present study, we show that nerve injury-induced miR-431 stimulates regenerative axon growth by silencing Kremen1, an antagonist of Wnt/beta-catenin signaling. Both the gain-of-function of miR-431 and knockdown of Kremen1 significantly enhance axon outgrowth in murine dorsal root ganglion neuronal cultures. Using cross-linking with AGO-2 immunoprecipitation, and 3′-untranslated region (UTR) luciferase reporter assay we demonstrate miR-431 direct interaction on the 3′-UTR of Kremen1 mRNA. Together, our results identify miR-431 as an important regulator of axonal regeneration and a promising therapeutic target. PMID:24167472

Variable gain for a wind turbine pitch control

NASA Technical Reports Server (NTRS)

Seidel, R. C.; Birchenough, A. G.

1981-01-01

The gain variation is made in the software logic of the pitch angle controller. The gain level is changed depending upon the level of power error. The control uses low gain for low pitch activity the majority of the time. If the power exceeds ten percent offset above rated, the gain is increased to a higher gain to more effectively limit power. A variable gain control functioned well in tests on the Mod-0 wind turbine.

Glucosamine enhances body weight gain and reduces insulin response in mice fed chow diet but mitigates obesity, insulin resistance and impaired glucose tolerance in mice high-fat diet.

PubMed

Hwang, Ji-Sun; Park, Ji-Won; Nam, Moon-Suk; Cho, Hyeongjin; Han, Inn-Oc

2015-03-01

This study investigated the potential of glucosamine (GlcN) to affect body weight gain and insulin sensitivity in mice normal and at risk for developing diabetes. Male C57BL/6J mice were fed either chow diet (CD) or a high fat diet (HFD) and the half of mice from CD and HFD provided with a solution of 10% (w/v) GlcN. Total cholesterol and nonesterified free fatty acid levels were determined. Glucose tolerance test and insulin tolerance test were performed. HepG2 human hepatoma cells or differentiated 3T3-L1 adipocytes were stimulated with insulin under normal (5 mM) or high glucose (25 mM) conditions. Effect of GlcN on 2-deoxyglucose (2-DG) uptake was determined. JNK and Akt phosphorylation and nucleocytoplasmic protein O-GlcNAcylation were assayed by Western blotting. GlcN administration stimulated body weight gain (6.58±0.82 g vs. 11.1±0.42 g), increased white adipose tissue fat mass (percentage of bodyweight, 3.7±0.32 g vs. 5.61±0.34 g), and impaired the insulin response in livers of mice fed CD. However, GlcN treatment in mice fed HFD led to reduction of body weight gain (18.02±0.66 g vs. 16.22±0.96 g) and liver weight (2.27±0.1 vs. 1.85±0.12 g). Furthermore, obesity-induced insulin resistance and impaired Akt insulin signaling in the liver were alleviated by GlcN administration. GlcN inhibited the insulin response under low (5 mM) glucose conditions, whereas it restored the insulin response for Akt phosphorylation under high (25 mM) glucose conditions in HepG2 and 3T3-L1 cells. Uptake of 2-DG increased upon GlcN treatment under 5 mM glucose compared to control, whereas insulin-stimulated 2-DG uptake decreased under 5 mM and increased under 25 mM glucose in differentiated 3T3-L1 cells. Our results show that GlcN increased body weight gain and reduced the insulin response for glucose maintenance when fed to normal CD mice, whereas it alleviated body weight gain and insulin resistance in HFD mice. Therefore, the current data support the integrative

Regulated Breathing Effect of Silicon Negative Electrode for Dramatically Enhanced Performance of Li-Ion Battery

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

Xiao, Xingcheng; Zhou, Weidong; Kim, Youngnam

Si is an attractive negative electrode material for lithium ion batteries due to its high specifi c capacity (≈3600 mAh g –1 ). However, the huge volume swelling and shrinking during cycling, which mimics a breathing effect at the material/electrode/cell level, leads to several coupled issues including fracture of Si particles, unstable solid electrolyte interphase, and low Coulombic effi ciency. In this work, the regulation of the breathing effect is reported by using Si–C yolk–shell nanocomposite which has been well-developed by other researchers. The focus is on understanding how the nanoscaled materials design impacts the mechanical and electrochemical response atmore » electrode level. For the fi rst time, it is possible to observe one order of magnitude of reduction on breathing effect at the electrode level during cycling: the electrode thickness variation reduced down to 10%, comparing with 100% in the electrode with Si nanoparticles as active materials. The Si–C yolk–shell nanocomposite electrode exhibits excellent capacity retention and high cycle effi ciency. In situ transmission electron microscopy and fi nite element simulations consistently reveals that the dramatically enhanced performance is associated with the regulated breathing of the Si in the new composite, therefore the suppression of the overall electrode expansion.« less

Contrast Gain Control in Auditory Cortex

PubMed Central

Rabinowitz, Neil C.; Willmore, Ben D.B.; Schnupp, Jan W.H.; King, Andrew J.

2011-01-01

Summary The auditory system must represent sounds with a wide range of statistical properties. One important property is the spectrotemporal contrast in the acoustic environment: the variation in sound pressure in each frequency band, relative to the mean pressure. We show that neurons in ferret auditory cortex rescale their gain to partially compensate for the spectrotemporal contrast of recent stimulation. When contrast is low, neurons increase their gain, becoming more sensitive to small changes in the stimulus, although the effectiveness of contrast gain control is reduced at low mean levels. Gain is primarily determined by contrast near each neuron's preferred frequency, but there is also a contribution from contrast in more distant frequency bands. Neural responses are modulated by contrast over timescales of ∼100 ms. By using contrast gain control to expand or compress the representation of its inputs, the auditory system may be seeking an efficient coding of natural sounds. PMID:21689603

Sertoli cell androgen receptor expression regulates temporal fetal and adult Leydig cell differentiation, function, and population size.

PubMed

Hazra, Rasmani; Jimenez, Mark; Desai, Reena; Handelsman, David J; Allan, Charles M

2013-09-01

We recently created a mouse model displaying precocious Sertoli cell (SC) and spermatogenic development induced by SC-specific transgenic androgen receptor expression (TgSCAR). Here we reveal that TgSCAR regulates the development, function, and absolute number of Leydig cells (LCs). Total fetal and adult type LC numbers were reduced in postnatal and adult TgSCAR vs control testes, despite normal circulating LH levels. Normal LC to SC ratios found in TgSCAR testes indicate that SC androgen receptor (SCAR)-mediated activity confers a quorum-dependent relationship between total SC and LC numbers. TgSCAR enhanced LC differentiation, shown by elevated ratios of advanced to immature LC types, and reduced LC proliferation in postnatal TgSCAR vs control testes. Postnatal TgSCAR testes displayed up-regulated expression of coupled ligand-receptor transcripts (Amh-Amhr2, Dhh-Ptch1, Pdgfa-Pdgfra) for potential SCAR-stimulated paracrine pathways, which may coordinate LC differentiation. Neonatal TgSCAR testes displayed normal T and dihydrotestosterone levels despite differential changes to steroidogenic gene expression, with down-regulated Star, Cyp11a1, and Cyp17a1 expression contrasting with up-regulated Hsd3b1, Hsd17b3, and Srd5a1 expression. TgSCAR males also displayed elevated postnatal and normal adult serum testosterone levels, despite reduced LC numbers. Enhanced adult-type LC steroidogenic output was revealed by increased pubertal testicular T, dihydrotestosterone, 3α-diol and 3β-diol levels per LC and up-regulated steroidogenic gene (Nr5a1, Lhr, Cyp11a1, Cyp17a1, Hsd3b6, Srd5a1) expression in pubertal or adult TgSCAR vs control males, suggesting regulatory mechanisms maintain androgen levels independently of absolute LC numbers. Our unique gain-of-function TgSCAR model has revealed that SCAR activity controls temporal LC differentiation, steroidogenic function, and population size.

Overexpression of NtPR-Q Up-Regulates Multiple Defense-Related Genes in Nicotiana tabacum and Enhances Plant Resistance to Ralstonia solanacearum.

PubMed

Tang, Yuanman; Liu, Qiuping; Liu, Ying; Zhang, Linli; Ding, Wei

2017-01-01

Various classes of plant pathogenesis-related proteins have been identified in the past several decades. PR-Q, a member of the PR3 family encoding chitinases, has played an important role in regulating plant resistance and preventing pathogen infection. In this paper, we functionally characterized NtPR-Q in tobacco plants and found that the overexpression of NtPR-Q in tobacco Yunyan87 resulted in higher resistance to Ralstonia solanacearum inoculation. Surprisingly, overexpression of NtPR-Q led to the activation of many defense-related genes, such as salicylic acid (SA)-responsive genes NtPR1a/c , NtPR2 and NtCHN50 , JA-responsive gene NtPR1b and ET production-associated genes NtACC Oxidase and NtEFE26 . Consistent with the role of NtPR-Q in multiple stress responses, NtPR-Q transcripts were induced by the exogenous hormones SA, ethylene and methyl jasmonate, which could enhance the resistance of tobacco to R. solanacearum . Collectively, our results suggested that NtPR-Q overexpression led to the up-regulation of defense-related genes and enhanced plant resistance to R. solanacearum infection.

Apigenin enhances skeletal muscle hypertrophy and myoblast differentiation by regulating Prmt7

PubMed Central

Jang, Young Jin; Son, Hyo Jeong; Choi, Yong Min; Ahn, Jiyun; Jung, Chang Hwa; Ha, Tae Youl

2017-01-01

Apigenin, a natural flavone abundant in various plant-derived foods including parsley and celery, has been shown to prevent inflammation and inflammatory diseases. However, the effect of apigenin on skeletal muscle hypertrophy and myogenic differentiation has not previously been elucidated. Here, we investigated the effects of apigenin on quadricep muscle weight and running distance using C57BL/6 mice on an accelerating treadmill. Apigenin stimulated mRNA expression of MHC (myosin heavy chain) 1, MHC2A, and MHC2B in the quadricep muscles of these animals. GPR56 (G protein-coupled receptor 56) and its ligand collagen III were upregulated by apigenin supplementation, together with enhanced PGC-1α, PGC-1α1, PGC-1α4, IGF1, and IGF2 expression. Prmt7 protein expression increased in conjunction with Akt and mTORC1 activation. Apigenin treatment also upregulated FNDC5 (fibronectin type III domain containing 5) mRNA expression and serum irisin levels. Furthermore, apigenin stimulated C2C12 myogenic differentiation and upregulated total MHC, MHC2A, and MHC2B expression. These events were attributable to an increase in Prmt7-p38-myoD expression and Akt and S6K1 phosphorylation. We also observed that Prmt7 regulates both PGC-1α1 and PGC-1α4 expression, resulting in a subsequent increase in GPR56 expression and mTORC1 activation. Taken together, these findings suggest that apigenin supplementation can promote skeletal muscle hypertrophy and myogenic differentiation by regulating the Prmt7-PGC-1α-GPR56 pathway, as well as the Prmt7-p38-myoD pathway, which may contribute toward the prevention of skeletal muscle weakness. PMID:29108230

Apigenin enhances skeletal muscle hypertrophy and myoblast differentiation by regulating Prmt7.

PubMed

Jang, Young Jin; Son, Hyo Jeong; Choi, Yong Min; Ahn, Jiyun; Jung, Chang Hwa; Ha, Tae Youl

2017-10-03

Apigenin, a natural flavone abundant in various plant-derived foods including parsley and celery, has been shown to prevent inflammation and inflammatory diseases. However, the effect of apigenin on skeletal muscle hypertrophy and myogenic differentiation has not previously been elucidated. Here, we investigated the effects of apigenin on quadricep muscle weight and running distance using C57BL/6 mice on an accelerating treadmill. Apigenin stimulated mRNA expression of MHC (myosin heavy chain) 1, MHC2A, and MHC2B in the quadricep muscles of these animals. GPR56 (G protein-coupled receptor 56) and its ligand collagen III were upregulated by apigenin supplementation, together with enhanced PGC-1α, PGC-1α1, PGC-1α4, IGF1, and IGF2 expression. Prmt7 protein expression increased in conjunction with Akt and mTORC1 activation. Apigenin treatment also upregulated FNDC5 (fibronectin type III domain containing 5) mRNA expression and serum irisin levels. Furthermore, apigenin stimulated C2C12 myogenic differentiation and upregulated total MHC, MHC2A, and MHC2B expression. These events were attributable to an increase in Prmt7-p38-myoD expression and Akt and S6K1 phosphorylation. We also observed that Prmt7 regulates both PGC-1α1 and PGC-1α4 expression, resulting in a subsequent increase in GPR56 expression and mTORC1 activation. Taken together, these findings suggest that apigenin supplementation can promote skeletal muscle hypertrophy and myogenic differentiation by regulating the Prmt7-PGC-1α-GPR56 pathway, as well as the Prmt7-p38-myoD pathway, which may contribute toward the prevention of skeletal muscle weakness.

Computer algorithm for coding gain

NASA Technical Reports Server (NTRS)

Dodd, E. E.

1974-01-01

Development of a computer algorithm for coding gain for use in an automated communications link design system. Using an empirical formula which defines coding gain as used in space communications engineering, an algorithm is constructed on the basis of available performance data for nonsystematic convolutional encoding with soft-decision (eight-level) Viterbi decoding.

Frequency chirping for resonance-enhanced electron energy during laser acceleration

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

Gupta, D.N.; Suk, H.

2006-04-15

The model given by Singh-Tripathi [Phys. Plasmas 11, 743 (2004)] for laser electron acceleration in a magnetic wiggler is revisited by including the effect of laser frequency chirping. Laser frequency chirp helps to maintain the resonance condition longer, which increases the electron energy gain. A significant enhancement in electron energy gain during laser acceleration is observed.

Sulforaphane activates heat shock response and enhances proteasome activity through up-regulation of Hsp27.

PubMed

Gan, Nanqin; Wu, Yu-Chieh; Brunet, Mathilde; Garrido, Carmen; Chung, Fung-Lung; Dai, Chengkai; Mi, Lixin

2010-11-12

It is conceivable that stimulating proteasome activity for rapid removal of misfolded and oxidized proteins is a promising strategy to prevent and alleviate aging-related diseases. Sulforaphane (SFN), an effective cancer preventive agent derived from cruciferous vegetables, has been shown to enhance proteasome activities in mammalian cells and to reduce the level of oxidized proteins and amyloid β-induced cytotoxicity. Here, we report that SFN activates heat shock transcription factor 1-mediated heat shock response. Specifically, SFN-induced expression of heat shock protein 27 (Hsp27) underlies SFN-stimulated proteasome activity. SFN-induced proteasome activity was significantly enhanced in Hsp27-overexpressing cells but absent in Hsp27-silenced cells. The role of Hsp27 in regulating proteasome activity was further confirmed in isogenic REG cells, in which SFN-induced proteasome activation was only observed in cells stably overexpressing Hsp27, but not in the Hsp27-free parental cells. Finally, we demonstrated that phosphorylation of Hsp27 is irrelevant to SFN-induced proteasome activation. This study provides a novel mechanism underlying SFN-induced proteasome activity. This is the first report to show that heat shock response by SFN, in addition to the antioxidant response mediated by the Keap1-Nrf2 pathway, may contribute to cytoprotection.

MicroRNA-26a/-26b-COX-2-MIP-2 Loop Regulates Allergic Inflammation and Allergic Inflammation-promoted Enhanced Tumorigenic and Metastatic Potential of Cancer Cells*

PubMed Central

Kwon, Yoojung; Kim, Youngmi; Eom, Sangkyung; Kim, Misun; Park, Deokbum; Kim, Hyuna; Noh, Kyeonga; Lee, Hansoo; Lee, Yun Sil; Choe, Jongseon; Kim, Young Myeong; Jeoung, Dooil

2015-01-01

Cyclooxgenase-2 (COX-2) knock-out mouse experiments showed that COX-2 was necessary for in vivo allergic inflammation, such as passive cutaneous anaphylaxis, passive systemic anaphylaxis, and triphasic cutaneous allergic reaction. TargetScan analysis predicted COX-2 as a target of miR-26a and miR-26b. miR-26a/-26b decreased luciferase activity associated with COX-2–3′-UTR. miR-26a/-26b exerted negative effects on the features of in vitro and in vivo allergic inflammation by targeting COX-2. ChIP assays showed the binding of HDAC3 and SNAIL, but not COX-2, to the promoter sequences of miR-26a and miR-26b. Cytokine array analysis showed that the induction of chemokines, such as MIP-2, in the mouse passive systemic anaphylaxis model occurred in a COX-2-dependent manner. ChIP assays showed the binding of HDAC3 and COX-2 to the promoter sequences of MIP-2. In vitro and in vivo allergic inflammation was accompanied by the increased expression of MIP-2. miR-26a/-26b negatively regulated the expression of MIP-2. Allergic inflammation enhanced the tumorigenic and metastatic potential of cancer cells and induced positive feedback involving cancer cells and stromal cells, such as mast cells, macrophages, and endothelial cells. miR-26a mimic and miR-26b mimic negatively regulated the positive feedback between cancer cells and stromal cells and the positive feedback among stromal cells. miR-26a/-26b negatively regulated the enhanced tumorigenic potential by allergic inflammation. COX-2 was necessary for the enhanced metastatic potential of cancer cells by allergic inflammation. Taken together, our results indicate that the miR26a/-26b-COX-2-MIP-2 loop regulates allergic inflammation and the feedback relationship between allergic inflammation and the enhanced tumorigenic and metastatic potential. PMID:25907560

Direct measurements of fluorine atom concentration, gain length and small signal gain in an hydrogen fluoride overtone laser

NASA Astrophysics Data System (ADS)

Wisniewski, Charles F.; Hewett, Kevin B.; Manke, Gerald C., II; Randall Truman, C.; Hager, Gordon D.

2003-03-01

Experimental techniques have been developed to directly measure the concentration of fluorine atoms, the gain length and the small signal gain in a hydrogen fluoride 5 cm slit nozzle laser. A gas phase titration technique was utilized to measure the fluorine atom concentration using HCl as the titrant. The gain length was measured using a pitot probe to locate the interface of the primary flow with the high Mach number shroud flows. A tunable diode laser was utilized to perform small signal gain measurements on HF overtone ( ν=2→0) transitions.

Decoy receptor 3 suppresses RANKL-induced osteoclastogenesis via down-regulating NFATc1 and enhancing cell apoptosis.

PubMed

Cheng, Chia-Pi; Sheu, Ming-Jen; Sytwu, Huey-Kang; Chang, Deh-Ming

2013-04-01

Decoy receptor 3 (DCR3) has been known to modulate immune functions of monocyte or macrophage. In the present study, we investigated the mechanism and the effect of DCR3 on RANK ligand (RANKL)-induced osteoclastogenesis. We treated cells with DCR3 in RANKL-induced osteoclastogenesis to monitor osteoclast formation by tartrate-resistant acid phosphatase (TRAP) staining. Osteoclast activity was assessed by pit formation assay. The mechanism of inhibition was studied by biochemical analysis such as RT-PCR and immunoblotting. In addition, cell viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Cell apoptosis and apoptosis signalling were evaluated by immunoblotting and using flow cytometry. DCR3 inhibited RANKL-induced TRAP(+) multinucleated cells and inhibited RANKL-induced nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation and nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1 (NFATc1) nuclear translocation in RAW264.7 cells. Also, DCR3 significantly inhibited the bone-resorbing activity of mature osteoclasts. Moreover, DCR3 enhanced RANKL-induced cell apoptosis and enhanced RANKL-induced Fas ligand expression. The mechanisms were mediated via the intrinsic cytochrome c and activated caspase 9 apoptosis pathway. We postulated that the inhibitory activity of DCR3 on osteoclastogenesis occurs via down-regulation of RANKL-induced NFATc1 expression and induction of cell apoptosis. Our results postulated DCR3 as a possible new remedy against inflammatory bone destruction.

Low Order Modeling Tools for Preliminary Pressure Gain Combustion Benefits Analyses

NASA Technical Reports Server (NTRS)

Paxson, Daniel E.

2012-01-01

Pressure gain combustion (PGC) offers the promise of higher thermodynamic cycle efficiency and greater specific power in propulsion and power systems. This presentation describes a model, developed under a cooperative agreement between NASA and AFRL, for preliminarily assessing the performance enhancement and preliminary size requirements of PGC components either as stand-alone thrust producers or coupled with surrounding turbomachinery. The model is implemented in the Numerical Propulsion Simulation System (NPSS) environment allowing various configurations to be examined at numerous operating points. The validated model is simple, yet physics-based. It executes quickly in NPSS, yet produces realistic results.

Gain-phase modulation in chirped-pulse amplification

NASA Astrophysics Data System (ADS)

Shen, Yijie; Gao, Gan; Meng, Yuan; Fu, Xing; Gong, Mali

2017-10-01

The cross-modulation between the gain and chirped phase in chirped-pulse amplification (CPA) is theoretically and experimentally demonstrated. We propose a gain-phase coupled nonlinear Schrödinger equation (GPC-NLSE) for solving chirped-pulse propagation in a nonlinear gain medium involved in the gain-phase modulation (GPM) process. With the GPC-NLSE, the space-time-frequency-dependent gain, chirped phase, pulse, and spectrum evolutions can be precisely calculated. Moreover, a short-length high-gain Yb-doped fiber CPA experiment is presented in which a self-steepening distortion of the seed pulse is automatically compensated after amplification. This phenomenon can be explained by the GPM theory whereas conventional models cannot. The experimental results for the temporal and spectral intensities show excellent agreement with our theory. Our GPM theory paves the way for further investigations of the finer structures of the pulse and spectrum in CPA systems.

Ultra-flat wideband single-pump Raman-enhanced parametric amplification.

PubMed

Gordienko, V; Stephens, M F C; El-Taher, A E; Doran, N J

2017-03-06

We experimentally optimize a single pump fiber optical parametric amplifier in terms of gain spectral bandwidth and gain variation (GV). We find that optimal performance is achieved with the pump tuned to the zero-dispersion wavelength of dispersion stable highly nonlinear fiber (HNLF). We demonstrate further improvement of parametric gain bandwidth and GV by decreasing the HNLF length. We discover that Raman and parametric gain spectra produced by the same pump may be merged together to enhance overall gain bandwidth, while keeping GV low. Consequently, we report an ultra-flat gain of 9.6 ± 0.5 dB over a range of 111 nm (12.8 THz) on one side of the pump. Additionally, we demonstrate amplification of a 60 Gbit/s QPSK signal tuned over a portion of the available bandwidth with OSNR penalty less than 1 dB for Q² below 14 dB.

Optimal PID gain schedule for hydrogenerators

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

Orelind, G.; Wozniak, L.; Medanic, J.

1989-09-01

This paper describes the development and testing of a digital gain switching governor for hydrogenerators. Optimal gains were found at different load points by minimizing a quadratic performance criterion prior to controller operating. During operation, the gain sets are switched in depending on the gate position and speed error magnitude. With gain switching operating, the digital governor was shown to have a substantial reduction of noise on the command signal and up to 42% faster responses to power requests. Non-linear control strategies enabled the digital governor to have a 2.5% to 2% reduction in speed overshoot on startups, and anmore » 8% to 1% reduction in undershoot on load rejections as compared to the analog.« less

Should performance-enhancing drugs in sport be legalized under medical supervision?

PubMed

Wiesing, Urban

2011-02-01

This review examines the question of whether performance-enhancing drugs should be permitted in sport under the control of physicians, and evaluates the expected outcomes of such a scenario. Such a change in regulation would need to be tightly controlled because of the risks involved. The results of legalizing performance-enhancing drugs in competitive sport would be either unhelpful or negative, and the unwanted aspects of doping control would not disappear. Athletes, including children and adolescents who wanted to pursue competitive sports, would be forced to take additional, avoidable health risks. The 'natural lottery' of athletic talents would be compensated for only partially by use of performance-enhancing agents. It would also be complemented by another 'natural lottery' of variable responses to doping measures, combined with the inventiveness of doping doctors. There would be no gain in 'justice' (i.e. fairer results that reflected efforts made) for athletes as a result of legalizing doping. Legalization would not reduce restrictions on athletes' freedom; the control effort would remain the same, if not increased. Extremely complicated international regulations would have to be adopted. The game of the 'tortoise and the hare' between doping athletes and inspectors would remain because prohibited but not identifiable practices could still provide additional benefits from use of permissible drugs. Audience mistrust, particularly toward athletes who achieved outstanding feats, would remain because it would still be possible that these athletes were reliant on illegal doping practices. Doping entails exposing the athletes to avoidable risks that do not need to be taken to increase the appeal of a sport. Most importantly, the function of sport as a role model would definitely be damaged. It is not necessary to clarify the question of what constitutes the 'spirit of sport' and whether this may be changed. From a practical point of view, a legalization of

Genome-wide characterization of mammalian promoters with distal enhancer functions.

PubMed

Dao, Lan T M; Galindo-Albarrán, Ariel O; Castro-Mondragon, Jaime A; Andrieu-Soler, Charlotte; Medina-Rivera, Alejandra; Souaid, Charbel; Charbonnier, Guillaume; Griffon, Aurélien; Vanhille, Laurent; Stephen, Tharshana; Alomairi, Jaafar; Martin, David; Torres, Magali; Fernandez, Nicolas; Soler, Eric; van Helden, Jacques; Puthier, Denis; Spicuglia, Salvatore

2017-07-01

Gene expression in mammals is precisely regulated by the combination of promoters and gene-distal regulatory regions, known as enhancers. Several studies have suggested that some promoters might have enhancer functions. However, the extent of this type of promoters and whether they actually function to regulate the expression of distal genes have remained elusive. Here, by exploiting a high-throughput enhancer reporter assay, we unravel a set of mammalian promoters displaying enhancer activity. These promoters have distinct genomic and epigenomic features and frequently interact with other gene promoters. Extensive CRISPR-Cas9 genomic manipulation demonstrated the involvement of these promoters in the cis regulation of expression of distal genes in their natural loci. Our results have important implications for the understanding of complex gene regulation in normal development and disease.

Sudden Gains During Therapy of Social Phobia

PubMed Central

Hofmann, Stefan G.; Schulz, Stefan M.; Meuret, Alicia E.; Moscovitch, David A.; Suvak, Michael

2007-01-01

The present study investigated the phenomenon of sudden gains in 107 participants with social phobia (social anxiety disorder) who received either cognitive–behavioral group therapy or exposure group therapy without explicit cognitive interventions, which primarily used public speaking situations as exposure tasks. Twenty-two out of 967 session-to-session intervals met criteria for sudden gains, which most frequently occurred in Session 5. Individuals with sudden gains showed similar improvements in the 2 treatment groups. Although cognitive–behavioral therapy was associated with more cognitive changes than exposure therapy, cognitive changes did not precede sudden gains. In general, the results of this study question the clinical significance of sudden gains in social phobia treatment. PMID:16881776

Interleukin-6 enhances cancer stemness and promotes metastasis of hepatocellular carcinoma via up-regulating osteopontin expression.

PubMed

Wang, Chao-Qun; Sun, Hao-Ting; Gao, Xiao-Mei; Ren, Ning; Sheng, Yuan-Yuan; Wang, Zheng; Zheng, Yan; Wei, Jin-Wang; Zhang, Kai-Li; Yu, Xin-Xin; Zhu, Yin; Luo, Qin; Yang, Lu-Yu; Dong, Qiong-Zhu; Qin, Lun-Xiu

2016-01-01

Interleukin-6 (IL-6), one of the most important inflammatory cytokines, plays a pivotal role in metastasis and stemness of solid tumors. However, the underlying mechanisms of IL-6 in HCC metastasis remain unclear. In the present study, we demonstrated that stemness and metastatic potential of HCC cells were significantly enhanced after IL-6 stimulation. IL-6 could induce expression of osteopontin (OPN), along with other stemness-related genes, including HIF1α, BMI1, and HEY1. Block of OPN induction could significantly abrogate the effect of IL-6 on stemness and metastasis of HCC cells. Furthermore, IL-6 level was positively correlated with OPN in HCC. Patients with high plasma IL-6 or OPN level had poorer prognosis. In multivariate analysis, IL-6 and OPN were demonstrated to be independent prognostic indicators for HCC patients, and their combination had a better prognostic performance than IL-6 or OPN alone. Collectively, our findings indicate that IL-6 could enhance stemness and promote metastasis of HCC via up-regulating OPN expression, which can be a potential therapeutic target for combating HCC metastasis, and the combination of IL-6 and OPN serves as a promising prognostic predictor for HCC.

Self-assembled DNA tetrahedral optofluidic lasers with precise and tunable gain control.

PubMed

Chen, Qiushu; Liu, Huajie; Lee, Wonsuk; Sun, Yuze; Zhu, Dan; Pei, Hao; Fan, Chunhai; Fan, Xudong

2013-09-07

We have applied self-assembled DNA tetrahedral nanostructures for the precise and tunable control of the gain in an optofluidic fluorescence resonance energy transfer (FRET) laser. By adjusting the ratio of the donor and the acceptor attached to the tetrahedral vertices, 3.8 times reduction in the lasing threshold and 28-fold enhancement in the lasing efficiency were demonstrated. This work takes advantage of the self-recognition and self-assembly capabilities of biomolecules with well-defined structures and addressability, enabling nano-engineering of the laser down to the molecular level.

Short-term variability in body weight predicts long-term weight gain1

PubMed Central

Lowe, Michael R; Feig, Emily H; Winter, Samantha R; Stice, Eric

2015-01-01

Background: Body weight in lower animals and humans is highly stable despite a very large flux in energy intake and expenditure over time. Conversely, the existence of higher-than-average variability in weight may indicate a disruption in the mechanisms responsible for homeostatic weight regulation. Objective: In a sample chosen for weight-gain proneness, we evaluated whether weight variability over a 6-mo period predicted subsequent weight change from 6 to 24 mo. Design: A total of 171 nonobese women were recruited to participate in this longitudinal study in which weight was measured 4 times over 24 mo. The initial 3 weights were used to calculate weight variability with the use of a root mean square error approach to assess fluctuations in weight independent of trajectory. Linear regression analysis was used to examine whether weight variability in the initial 6 mo predicted weight change 18 mo later. Results: Greater weight variability significantly predicted amount of weight gained. This result was unchanged after control for baseline body mass index (BMI) and BMI change from baseline to 6 mo and for measures of disinhibition, restrained eating, and dieting. Conclusions: Elevated weight variability in young women may signal the degradation of body weight regulatory systems. In an obesogenic environment this may eventuate in accelerated weight gain, particularly in those with a genetic susceptibility toward overweight. Future research is needed to evaluate the reliability of weight variability as a predictor of future weight gain and the sources of its predictive effect. The trial on which this study is based is registered at clinicaltrials.gov as NCT00456131. PMID:26354535

A novel digital image sensor with row wise gain compensation for Hyper Spectral Imager (HySI) application

NASA Astrophysics Data System (ADS)

Lin, Shengmin; Lin, Chi-Pin; Wang, Weng-Lyang; Hsiao, Feng-Ke; Sikora, Robert

2009-08-01

A 256x512 element digital image sensor has been developed which has a large pixel size, slow scan and low power consumption for Hyper Spectral Imager (HySI) applications. The device is a mixed mode, silicon on chip (SOC) IC. It combines analog circuitry, digital circuitry and optical sensor circuitry into a single chip. This chip integrates a 256x512 active pixel sensor array, a programming gain amplifier (PGA) for row wise gain setting, I2C interface, SRAM, 12 bit analog to digital convertor (ADC), voltage regulator, low voltage differential signal (LVDS) and timing generator. The device can be used for 256 pixels of spatial resolution and 512 bands of spectral resolution ranged from 400 nm to 950 nm in wavelength. In row wise gain readout mode, one can set a different gain on each row of the photo detector by storing the gain setting data on the SRAM thru the I2C interface. This unique row wise gain setting can be used to compensate the silicon spectral response non-uniformity problem. Due to this unique function, the device is suitable for hyper-spectral imager applications. The HySI camera located on-board the Chandrayaan-1 satellite, was successfully launched to the moon on Oct. 22, 2008. The device is currently mapping the moon and sending back excellent images of the moon surface. The device design and the moon image data will be presented in the paper.

Are videogame training gains specific or general?

PubMed

Oei, Adam C; Patterson, Michael D

2014-01-01

Many recent studies using healthy adults document enhancements in perception and cognition from playing commercial action videogames (AVGs). Playing action games (e.g., Call of Duty, Medal of Honor) is associated with improved bottom-up lower-level information processing skills like visual-perceptual and attentional processes. One proposal states a general improvement in the ability to interpret and gather statistical information to predict future actions which then leads to better performance across different perceptual/attentional tasks. Another proposal claims all the tasks are separately trained in the AVGs because the AVGs and laboratory tasks contain similar demands. We review studies of action and non-AVGs to show support for the latter proposal. To explain transfer in AVGs, we argue that the perceptual and attention tasks share common demands with the trained videogames (e.g., multiple object tracking (MOT), rapid attentional switches, and peripheral vision). In non-AVGs, several studies also demonstrate specific, limited transfer. One instance of specific transfer is the specific enhancement to mental rotation after training in games with a spatial emphasis (e.g., Tetris). In contrast, the evidence for transfer is equivocal where the game and task do not share common demands (e.g., executive functioning). Thus, the "common demands" hypothesis of transfer not only characterizes transfer effects in AVGs, but also non-action games. Furthermore, such a theory provides specific predictions, which can help in the selection of games to train human cognition as well as in the design of videogames purposed for human cognitive and perceptual enhancement. Finally this hypothesis is consistent with the cognitive training literature where most post-training gains are for tasks similar to the training rather than general, non-specific improvements.

Are videogame training gains specific or general?

PubMed Central

Patterson, Michael D.

2014-01-01

Many recent studies using healthy adults document enhancements in perception and cognition from playing commercial action videogames (AVGs). Playing action games (e.g., Call of Duty, Medal of Honor) is associated with improved bottom-up lower-level information processing skills like visual-perceptual and attentional processes. One proposal states a general improvement in the ability to interpret and gather statistical information to predict future actions which then leads to better performance across different perceptual/attentional tasks. Another proposal claims all the tasks are separately trained in the AVGs because the AVGs and laboratory tasks contain similar demands. We review studies of action and non-AVGs to show support for the latter proposal. To explain transfer in AVGs, we argue that the perceptual and attention tasks share common demands with the trained videogames (e.g., multiple object tracking (MOT), rapid attentional switches, and peripheral vision). In non-AVGs, several studies also demonstrate specific, limited transfer. One instance of specific transfer is the specific enhancement to mental rotation after training in games with a spatial emphasis (e.g., Tetris). In contrast, the evidence for transfer is equivocal where the game and task do not share common demands (e.g., executive functioning). Thus, the “common demands” hypothesis of transfer not only characterizes transfer effects in AVGs, but also non-action games. Furthermore, such a theory provides specific predictions, which can help in the selection of games to train human cognition as well as in the design of videogames purposed for human cognitive and perceptual enhancement. Finally this hypothesis is consistent with the cognitive training literature where most post-training gains are for tasks similar to the training rather than general, non-specific improvements. PMID:24782722

Transformer-Feedback Interstage Bandwidth Enhancement for MMIC Multistage Amplifiers

NASA Astrophysics Data System (ADS)

Nikandish, Gholamreza; Medi, Ali

2015-02-01

The transformer-feedback (TRFB) interstage bandwidth enhancement technique for broadband multistage amplifiers is presented. Theory of the TRFB bandwidth enhancement and the design conditions for maximum bandwidth, maximally flat gain, and maximally flat group delay are provided. It is shown that the TRFB bandwidth enhancement can provide higher bandwidth compared to the conventional techniques based on reactive impedance matching networks. A three-stage low-noise amplifier (LNA) monolithic microwave integrated circuit with the TRFB between its consecutive stages is designed and implemented in a 0.1- μm GaAs pHEMT process. The TRFB is realized by coupling between the drain bias lines of transistors. The reuse of bias lines leads to bandwidth enhancement without increasing the chip area and power consumption. The LNA features average gain of 23 dB and 3-dB bandwidth of 11-39 GHz. It provides a noise figure of 2.1-3.0 dB and an output 1-dB compression point of 8.6 dBm, while consuming 40 mA of current from a 2-V supply.

A structured observation of behavioral self-regulation and its contribution to kindergarten outcomes.

PubMed

Ponitz, Claire Cameron; McClelland, Megan M; Matthews, J S; Morrison, Frederick J

2009-05-01

The authors examined a new assessment of behavioral regulation and contributions to achievement and teacher-rated classroom functioning in a sample (N = 343) of kindergarteners from 2 geographical sites in the United States. Behavioral regulation was measured with the Head-Toes-Knees-Shoulders (HTKS) task, a structured observation requiring children to perform the opposite of a dominant response to 4 different oral commands. Results revealed considerable variability in HTKS scores. Evidence for construct validity was found in positive correlations with parent ratings of attentional focusing and inhibitory control and teacher ratings of classroom behavioral regulation. Hierarchical linear modeling indicated that higher levels of behavioral regulation in the fall predicted stronger levels of achievement in the spring and better teacher-rated classroom self-regulation (all ps < .01) but not interpersonal skills. Evidence for domain specificity emerged, in which gains in behavioral regulation predicted gains in mathematics but not in language and literacy over the kindergarten year (p < .01) after site, child gender, and other background variables were controlled. Discussion focuses on the importance of behavioral regulation for successful adjustment to the demands of kindergarten. Copyright 2009 APA, all rights reserved

The effects of temperature, hydrostatic pressure and size on optical gain for GaAs spherical quantum dot laser with hydrogen impurity

NASA Astrophysics Data System (ADS)

Owji, Erfan; Keshavarz, Alireza; Mokhtari, Hosein

2016-10-01

In this paper, the effects of temperature, hydrostatic pressure and size on optical gain for GaAs spherical quantum dot laser with hydrogen impurity are investigated. For this purpose, the effects of temperature, pressure and quantum dot size on the band gap energy, effective mass, and dielectric constant are studied. The eigenenergies and eigenstates for valence and conduction band are calculated by using Runge-Kutta numerical method. Results show that changes in the temperature, pressure and size lead to the alteration of the band gap energy and effective mass. Also, increasing the temperature redshifts the optical gain peak and at special temperature ranges lead to increasing or decreasing of it. Further, by reducing the size, temperature-dependent of optical gain is decreased. Additionally, enhancing of the hydrostatic pressure blueshifts the peak of optical gain, and its behavior as a function of pressure which depends on the size. Finally, increasing the radius rises the redshifts of the peak of optical gain.

Epigenetic regulation of spinal cord gene expression contributes to enhanced postoperative pain and analgesic tolerance subsequent to continuous opioid exposure

PubMed Central

Liang, De-Yong; Shi, Xiao-You; Sun, Yuan; Clark, J David

2016-01-01

Background Opioids have become the mainstay for treatment of moderate to severe pain and are commonly used to treat surgical pain. While opioid administration has been shown to cause opioid-induced hyperalgesia and tolerance, interactions between opioid administration and surgery with respect to these problematic adaptations have scarcely been addressed. Accumulating evidence suggests opioids and nociceptive signaling may converge on epigenetic mechanisms in spinal cord to enhance or prolong neuroplastic changes. Epigenetic regulation of Bdnf (brain-derived neurotrophic factor) and Pdyn (prodynorphin) genes may be involved. Results Four days of ascending doses of morphine treatment caused opioid-induced hyperalgesia and reduced opioid analgesic efficacy in mice. Both opioid-induced hyperalgesia and the reduced opioid analgesic efficacy were enhanced in mice that received hindpaw incisions. The expression of Bdnf and Pdyn (qPCR) was increased after morphine treatment and incision. Chromatin immunoprecipitation assays demonstrated that the Pdyn and Bdnf promoters were more strongly associated with acetylated H3K9 after morphine plus incision than in the morphine or incision alone groups. Selective tropomyosin-related kinase B (ANA-12) and κ-opioid receptor (nor-binaltorphimine) antagonists were administered intrathecally, both reduced hyperalgesia one or three days after surgery. Administration of ANA-12 or nor-binaltorphimine attenuated the decreased morphine analgesic efficacy on day 1, but only nor-binaltorphimine was effective on day 3 after incision in opioid-exposed group. Coadministration of histone acetyltransferase inhibitor anacardic acid daily with morphine blocked the development of opioid-induced hyperalgesia and attenuated incision-enhanced hyperalgesia in morphine-treated mice. Anacardic acid had similar effects on analgesic tolerance, showing the involvement of histone acetylation in the interactions detected. Conclusions Spinal epigenetic changes

Epigenetic regulation of spinal cord gene expression contributes to enhanced postoperative pain and analgesic tolerance subsequent to continuous opioid exposure.

PubMed

Sahbaie, Peyman; Liang, De-Yong; Shi, Xiao-You; Sun, Yuan; Clark, J David

2016-01-01

Opioids have become the mainstay for treatment of moderate to severe pain and are commonly used to treat surgical pain. While opioid administration has been shown to cause opioid-induced hyperalgesia and tolerance, interactions between opioid administration and surgery with respect to these problematic adaptations have scarcely been addressed. Accumulating evidence suggests opioids and nociceptive signaling may converge on epigenetic mechanisms in spinal cord to enhance or prolong neuroplastic changes. Epigenetic regulation of Bdnf (brain-derived neurotrophic factor) and Pdyn (prodynorphin) genes may be involved. Four days of ascending doses of morphine treatment caused opioid-induced hyperalgesia and reduced opioid analgesic efficacy in mice. Both opioid-induced hyperalgesia and the reduced opioid analgesic efficacy were enhanced in mice that received hindpaw incisions. The expression of Bdnf and Pdyn (qPCR) was increased after morphine treatment and incision. Chromatin immunoprecipitation assays demonstrated that the Pdyn and Bdnf promoters were more strongly associated with acetylated H3K9 after morphine plus incision than in the morphine or incision alone groups. Selective tropomyosin-related kinase B (ANA-12) and κ-opioid receptor (nor-binaltorphimine) antagonists were administered intrathecally, both reduced hyperalgesia one or three days after surgery. Administration of ANA-12 or nor-binaltorphimine attenuated the decreased morphine analgesic efficacy on day 1, but only nor-binaltorphimine was effective on day 3 after incision in opioid-exposed group. Coadministration of histone acetyltransferase inhibitor anacardic acid daily with morphine blocked the development of opioid-induced hyperalgesia and attenuated incision-enhanced hyperalgesia in morphine-treated mice. Anacardic acid had similar effects on analgesic tolerance, showing the involvement of histone acetylation in the interactions detected. Spinal epigenetic changes involving Bdnf and Pdyn may

Autophagy inhibition enhances silibinin-induced apoptosis by regulating reactive oxygen species production in human prostate cancer PC-3 cells.

PubMed

Kim, Sang-Hun; Kim, Kwang-Youn; Yu, Sun-Nyoung; Park, Seul-Ki; Choi, Hyeun-Deok; Ji, Jae-Hoon; Ahn, Soon-Cheol

Silibinin is a major bioactive component of silymarin and has anticancer effects on cancer cell line and has been used as a supportive therapy for chronic inflammatory liver condition. These anticancer effects of silibinin have been demonstrated both in vitro and in vivo cancer models. Although various evidences showed apoptosis signaling pathways by silibinin, there is no report to address the clearly mechanism of silibinin-induced autophagy in prostate cancer PC-3 cells. Our study showed that silibinin triggered autophagy through up-regulation of microtubule-associated protein 1 light chain 3 (LC3)-II, formation of acidic vesicular organelles (AVO) and punctuate of GFP-LC3, which was inhibited by 3-methyladenine (3-MA), an inhibitor of specific autophagy. In addition, silibinin induced autophagy through production of reactive oxygen species (ROS). Inhibition of ROS with diphenyleneiodonium (DPI), a ROS inhibitor, attenuated silibinin-triggered autophagy. Inhibition of autophagy with 3-MA enhanced the silibinin-induced apoptosis through the regulation of caspase-3 and PARP. These results suggested that silibinin induced autophagy by regulating ROS and its mechanism played a protective role against apoptosis in PC-3 cells. Copyright © 2015 Elsevier Inc. All rights reserved.

Enhancing Exposure Therapy for Anxiety Disorders, Obsessive Compulsive Disorder, and Posttraumatic Stress Disorder

PubMed Central

McGuire, Joseph F.; Lewin, Adam B.; Storch, Eric A.

2014-01-01

Translating findings from basic science, several compounds have been identified that may enhance therapeutic outcomes and/or expedite treatment gains when administered alongside exposure-based treatments. Four of these compounds (referred to as cognitive enhancers) have been evaluated in the context of randomized controlled trials for anxiety disorders (e.g., specific phobias, panic disorder, social anxiety disorder), obsessive compulsive disorder (OCD), and posttraumatic stress disorder (PTSD). These cognitive enhancers include D-cycloserine, yohimbine hydrochloride, glucocorticoids and cortisol, and brain derived neurotrophic factor. There is consistent evidence that cognitive enhancers can enhance therapeutic outcomes and/or expedite treatment gains across anxiety disorders, OCD, and PTSD. Emerging evidence has highlighted the importance of within-session fear habituation and between-session fear learning, which can either enhance fear extinction or reconsolidate of fear responses. Although findings from these trials are promising, there are several considerations that warrant further evaluation prior to wide-spread use of cognitive enhancers in exposure-based treatments. Consistent trial design and large sample sizes are important in future studies of cognitive enhancers. PMID:24972729

The Power of the Virtual Ideal Self in Weight Control: Weight-Reduced Avatars Can Enhance the Tendency to Delay Gratification and Regulate Dietary Practices.

PubMed

Kuo, Hsu-Chan; Lee, Chun-Chia; Chiou, Wen-Bin

2016-02-01

The tendency to discount larger future benefits in favor of smaller immediate gains (i.e., temporal discounting) is relevant to the issue of obesity. Successful weight loss requires individuals to sacrifice immediate culinary pleasures in favor of future health gains. Based on the notion that increasing the vividness of one's future self may mitigate temporal discounting and promote the ability to delay gratification, we examined whether viewing one's weight-reduced self (i.e., the ideal self) in a virtual environment can decrease temporal discounting and lead to better regulation of dietary practices. Seventy-six undergraduates who had reported an intention to lose weight were recruited to participate in a laboratory experiment and were randomly assigned to interact with either the weight-reduced self (experimental condition) or the present self (control condition) by looking into a dressing mirror in a virtual fitting room. A temporal-discounting task and a taste test were subsequently administered. Results showed that, compared with control participants, participants who viewed their weight-reduced avatars ate less ice cream in a taste test and were more likely to choose a sugar-free drink as a reward. The discounting rate mediated the association between the avatar manipulation and the amount of ice cream eaten in the subsequent taste test. Overall, our findings suggest that a computer-generated image of one's weight-reduced self may assist in resisting impulses that promote immediate gratification over delayed benefits. This research provides a new approach for controlling impulsive behavior such as dietary regulation and weight control.

Performance scaling via passive pulse shaping in cavity-enhanced optical parametric chirped-pulse amplification.

PubMed

Siddiqui, Aleem M; Moses, Jeffrey; Hong, Kyung-Han; Lai, Chien-Jen; Kärtner, Franz X

2010-06-15

We show that an enhancement cavity seeded at the full repetition rate of the pump laser can automatically reshape small-signal gain across the interacting pulses in an optical parametric chirped-pulse amplifier for close-to-optimal operation, significantly increasing both the gain bandwidth and the conversion efficiency, in addition to boosting gain for high-repetition-rate amplification. Applied to a degenerate amplifier, the technique can provide an octave-spanning gain bandwidth.

Abbreviated Resonant Frequency Training to Augment Heart Rate Variability and Enhance On-Demand Emotional Regulation in Elite Sport Support Staff.

PubMed

Gross, Mike J; Shearer, David A; Bringer, Joy D; Hall, Ross; Cook, Christian J; Kilduff, Liam P

2016-09-01

Support and management staff in elite sport experience work-related stress and emotional disturbance to a similar extent as athletes (Fletcher and Wagstaff 2009). The resonant frequency breathing technique (Lehrer et al. 2000) can inhibit autonomic changes associated with stressful situations or events and as such provides a potential emotional regulation tool. The present study utilised five practitioner-led heart rate variability (HRV) biofeedback sessions and home practice via mobile applications to train support and management staff (n = 9) in resonant frequency breathing techniques. Although baseline HRV did not change from pre to post training, participants increased total HRV (i.e., SDNN; p = .006), parasympathetic HRV (i.e., RMSSD; p = .028) and HRV reflective of baroreflex function (i.e., low frequency power; p = .018) while accurately performing resonant frequency breathing without a breath pacer. Post-intervention questionnaire data revealed an increase (p = .032) in habitual use of somatic strategies for emotional regulation, and social validation data suggested that the technique enhanced emotional regulation at home, work and during international competition. HRV biofeedback and the resonant frequency technique provided an on-demand emotional regulation technique for elite sport support and management staff.

Realization of a gain with electromagnetically induced transparency system using non-degenerate Zeeman sublevels in 87 Rb

NASA Astrophysics Data System (ADS)

Zhou, Minchuan; Zhou, Zifan; Shahriar, Selim M.

2017-11-01

Previously, we had proposed an optically-pumped five-level Gain EIT (GEIT) system, which has a transparency dip superimposed on a gain profile and exhibits a negative dispersion suitable for the white-light-cavity signal-recycling (WLC-SR) scheme of the interferometric gravitational wave detector (Zhou et al., 2015). Using this system as the negative dispersion medium (NDM) in the WLC-SR, we get an enhancement in the quantum noise (QN) limited sensitivity-bandwidth product by a factor of ∼ 18. Here, we show how to realize this GEIT system in a realistic platform, using non-degenerate Zeeman sublevels in cold Rb atoms, employing anomalous dispersion at 795 nm. Using the Caves model for a phase insensitive linear amplifier, we show that an enhancement of the sensitivity-bandwidth product by a factor of ∼ 17 is possible for potentially realizable experimental parameters. While the current LIGO apparatus uses light at 1064 nm, a future embodiment thereof may operate at a wavelength that is consistent with the wavelength considered here.

Weight gain - unintentional

MedlinePlus

... Cushing syndrome Underactive thyroid, or low thyroid (hypothyroidism) Polycystic ovary syndrome Menopause Pregnancy Bloating, or swelling due to a buildup of fluid in the tissues can cause weight gain. This may be due to menstruation, heart ...

Parent-offspring conflict theory, signaling of need, and weight gain in early life.

PubMed

Wells, Jonathan C

2003-06-01

Human growth in early life has major implications for fitness. During this period, the mother regulates the growth of her offspring through placental nutrition and lactation. However, parent-offspring conflict theory predicts that offspring are selected to demand more resources than the mother is selected to provide. This general issue has prompted the development of begging theory, which attempts to find the optimal levels of offspring demand and parental provisioning. Several models have been proposed to account for begging behavior, whether by biochemical or behavioral pathways, including: (1) blackmail of parents; (2) scramble competition between multiple offspring; (3) honest signaling of nutritional need; and (4) honest signaling of offspring worth. These models are all supported by data from nonhuman animals, with species varying according to which model is relevant. This paper examines the evidence that human suckling and crying signal nutritional demand, need, and worth to the mother. While suckling provides hormonal stimulation of breast milk production and signals hunger, crying fulfills a different role, with evidence suggesting that it signals both worth and need for resources (nutrition and thermoregulation). The role of signaling in nutritional demand is examined in the context of three common health problems that have traditionally been assumed to have physiological rather than behavioral causes: excess weight gain, failure to thrive, and colic. The value of such an evolutionary approach lies in its potential to enhance behavioral management of these conditions.

New intelligent multifunctional SiO2/VO2 composite films with enhanced infrared light regulation performance, solar modulation capability, and superhydrophobicity

NASA Astrophysics Data System (ADS)

Wang, Chao; Zhao, Li; Liang, Zihui; Dong, Binghai; Wan, Li; Wang, Shimin

2017-12-01

Highly transparent, energy-saving, and superhydrophobic nanostructured SiO2/VO2 composite films have been fabricated using a sol-gel method. These composite films are composed of an underlying infrared (IR)-regulating VO2 layer and a top protective layer that consists of SiO2 nanoparticles. Experimental results showed that the composite structure could enhance the IR light regulation performance, solar modulation capability, and hydrophobicity of the pristine VO2 layer. The transmittance of the composite films in visible region (Tlum) was higher than 60%, which was sufficient to meet the requirements of glass lighting. Compared with pristine VO2 films and tungsten-doped VO2 film, the near IR control capability of the composite films was enhanced by 13.9% and 22.1%, respectively, whereas their solar modulation capability was enhanced by 10.9% and 22.9%, respectively. The water contact angles of the SiO2/VO2 composite films were over 150°, indicating superhydrophobicity. The transparent superhydrophobic surface exhibited a high stability toward illumination as all the films retained their initial superhydrophobicity even after exposure to 365 nm light with an intensity of 160 mW.cm-2 for 10 h. In addition, the films possessed anti-oxidation and anti-acid properties. These characteristics are highly advantageous for intelligent windows or solar cell applications, given that they can provide surfaces with anti-fogging, rainproofing, and self-cleaning effects. Our technique offers a simple and low-cost solution to the development of stable and visible light transparent superhydrophobic surfaces for industrial applications.

New intelligent multifunctional SiO2/VO2 composite films with enhanced infrared light regulation performance, solar modulation capability, and superhydrophobicity.

PubMed

Wang, Chao; Zhao, Li; Liang, Zihui; Dong, Binghai; Wan, Li; Wang, Shimin

2017-01-01

Highly transparent, energy-saving, and superhydrophobic nanostructured SiO 2 /VO 2 composite films have been fabricated using a sol-gel method. These composite films are composed of an underlying infrared (IR)-regulating VO 2 layer and a top protective layer that consists of SiO 2 nanoparticles. Experimental results showed that the composite structure could enhance the IR light regulation performance, solar modulation capability, and hydrophobicity of the pristine VO 2 layer. The transmittance of the composite films in visible region ( T lum ) was higher than 60%, which was sufficient to meet the requirements of glass lighting. Compared with pristine VO 2 films and tungsten-doped VO 2 film, the near IR control capability of the composite films was enhanced by 13.9% and 22.1%, respectively, whereas their solar modulation capability was enhanced by 10.9% and 22.9%, respectively. The water contact angles of the SiO 2 /VO 2 composite films were over 150°, indicating superhydrophobicity. The transparent superhydrophobic surface exhibited a high stability toward illumination as all the films retained their initial superhydrophobicity even after exposure to 365 nm light with an intensity of 160 mW . cm -2 for 10 h. In addition, the films possessed anti-oxidation and anti-acid properties. These characteristics are highly advantageous for intelligent windows or solar cell applications, given that they can provide surfaces with anti-fogging, rainproofing, and self-cleaning effects. Our technique offers a simple and low-cost solution to the development of stable and visible light transparent superhydrophobic surfaces for industrial applications.

Callose biosynthesis regulates symplastic trafficking during root development.

PubMed

Vatén, Anne; Dettmer, Jan; Wu, Shuang; Stierhof, York-Dieter; Miyashima, Shunsuke; Yadav, Shri Ram; Roberts, Christina J; Campilho, Ana; Bulone, Vincent; Lichtenberger, Raffael; Lehesranta, Satu; Mähönen, Ari Pekka; Kim, Jae-Yean; Jokitalo, Eija; Sauer, Norbert; Scheres, Ben; Nakajima, Keiji; Carlsbecker, Annelie; Gallagher, Kimberly L; Helariutta, Ykä

2011-12-13

Plant cells are connected through plasmodesmata (PD), membrane-lined channels that allow symplastic movement of molecules between cells. However, little is known about the role of PD-mediated signaling during plant morphogenesis. Here, we describe an Arabidopsis gene, CALS3/GSL12. Gain-of-function mutations in CALS3 result in increased accumulation of callose (β-1,3-glucan) at the PD, a decrease in PD aperture, defects in root development, and reduced intercellular trafficking. Enhancement of CALS3 expression during phloem development suppressed loss-of-function mutations in the phloem abundant callose synthase, CALS7 indicating that CALS3 is a bona fide callose synthase. CALS3 alleles allowed us to spatially and temporally control the PD aperture between plant tissues. Using this tool, we are able to show that movement of the transcription factor SHORT-ROOT and microRNA165 between the stele and the endodermis is PD dependent. Taken together, we conclude that regulated callose biosynthesis at PD is essential for cell signaling. Copyright © 2011 Elsevier Inc. All rights reserved.

High Efficiency Automatic-Power-Controlled and Gain-Clamped EDFA for Broadband Passive Optical Networking Systems

NASA Astrophysics Data System (ADS)

Shen, Jyi-Lai; Wei, Shui-Ken; Lin, Chin-Yuan; Iong Li, Ssu; Huang, Chih-Chuan

2010-04-01

The configuration of a simple improved high efficiency automatic-power-controlled and gain-clamped EDFA (APC-GC-EDFA) for broadband passive optical networking systems (BPON) is presented here. In order to compensate the phase and amplitude variation due to the different distance between the optical line terminal (OLT) and optical network units (ONU), the APC-GC-EDFA need to be employed. A single 980 nm laser module is employed as the primary pump. To extend the bandwidth, all C-band ASE is recycled as the secondary pump to enhance the gain efficiency. An electrical feedback circuit is used as a multi-wavelength channel transmitter monitor for the automatic power control to improve the gain-flattened flatness for stable amplification. The experimental results prove that the EDFA system can provide flatter clamped gain in both C-band and L-band configurations. The gain flatness wavelength ranging from 1530 to 1610 nm is within 32.83 ± 0.64 dB, i.e. below 1.95 %. The gains are clamped at 33.85 ± 0.65 dB for the input signal power of -40 dBm to -10 dBm. The range of noise figure is between 6.37 and 6.56, which is slightly lower compared to that of unclamped amplifiers. This will be very useful for measuring the gain flatness of APC-GC-EDFA. Finally, we have also demonstrated the records of the overall simultaneous dynamics measurements for the new system stabilization. The carrier to noise ratio (CNR) is 49.5 to 50.8 dBc which is above the National Television System Committee (NTSC) standard of 43 dBc, and both composite second order (CSO) 69.2 to 71.5 dBc and composite triple beat (CTB) of 69.8 to 72.2 dBc are above 53 dBc. The recorded corresponding rise-time of 1.087 ms indicates that the system does not exhibit any overshoot of gain or ASE variation due to the signal at the beginning of the pulse.

HIF-1α regulates epithelial inflammation by cell autonomous NFκB activation and paracrine stromal remodeling

PubMed Central

Scortegagna, Marzia; Cataisson, Christophe; Martin, Rebecca J.; Hicklin, Daniel J.; Schreiber, Robert D.; Yuspa, Stuart H.

2008-01-01

Hypoxia inducible factor-1 (HIF-1) is a master regulatory transcription factor controlling multiple cell-autonomous and non–cell-autonomous processes, such as metabolism, angiogenesis, matrix invasion, and cancer metastasis. Here we used a new line of transgenic mice with constitutive gain of HIF-1 function in basal keratinocytes and demonstrated a signaling pathway from HIF-1 to nuclear factor κ B (NFκB) activation to enhanced epithelial chemokine and cytokine elaboration. This pathway was responsible for a phenotypically silent accumulation of stromal inflammatory cells and a marked inflammatory hypersensitivity to a single 12-O-tetradecanoylphorbol-13-acetate (TPA) challenge. HIF-1–induced NFκB activation was composed of 2 elements, IκB hyperphosphorylation and phosphorylation of Ser276 on p65, enhancing p65 nuclear localization and transcriptional activity, respectively. NFκB transcriptional targets macrophage inflammatory protein-2 (MIP-2/CXCL2/3), keratinocyte chemokine (KC/CXCL1), and tumor necrosis factor [alfa] (TNFα) were constitutively up-regulated and further increased after TPA challenge both in cultured keratinocytes and in transgenic mice. Whole animal KC, MIP-2, or TNFα immunodepletion each abrogated TPA-induced inflammation, whereas blockade of either VEGF or placenta growth factor (PlGF) signaling did not affect transgenic inflammatory hyper-responsiveness. Thus, epithelial HIF-1 gain of function remodels the local environment by cell-autonomous NFκB-mediated chemokine and cytokine secretion, which may be another mechanism by which HIF-1 facilitates either inflammatory diseases or malignant progression. PMID:18199827

Enhancing Diversity in Undergraduate Science: Self-Efficacy Drives Performance Gains with Active Learning

PubMed Central

Ballen, Cissy J.; Wieman, Carl; Salehi, Shima; Searle, Jeremy B.; Zamudio, Kelly R.

2017-01-01

Efforts to retain underrepresented minority (URM) students in science, technology, engineering, and mathematics (STEM) have shown only limited success in higher education, due in part to a persistent achievement gap between students from historically underrepresented and well-represented backgrounds. To test the hypothesis that active learning disproportionately benefits URM students, we quantified the effects of traditional versus active learning on student academic performance, science self-efficacy, and sense of social belonging in a large (more than 250 students) introductory STEM course. A transition to active learning closed the gap in learning gains between non-URM and URM students and led to an increase in science self-efficacy for all students. Sense of social belonging also increased significantly with active learning, but only for non-URM students. Through structural equation modeling, we demonstrate that, for URM students, the increase in self-efficacy mediated the positive effect of active-learning pedagogy on two metrics of student performance. Our results add to a growing body of research that supports varied and inclusive teaching as one pathway to a diversified STEM workforce. PMID:29054921

Is Weight Gain after Smoking Cessation Inevitable?

ERIC Educational Resources Information Center

Talcott, Gerald W.; And Others

1995-01-01

Studied weight gain after smoking cessation in a naturalistic setting where all smokers quit and risk factors for postcessation weight gain were modified. Results showed no significant weight changes for smokers who quit. Suggests that an intensive program featuring dietary guidelines and increased physical activity can attenuate weight gain. (RJM)

The same enhancer regulates the earliest Emx2 expression in caudal forebrain primordium, subsequent expression in dorsal telencephalon and later expression in the cortical ventricular zone.

PubMed

Suda, Yoko; Kokura, Kenji; Kimura, Jun; Kajikawa, Eriko; Inoue, Fumitaka; Aizawa, Shinichi

2010-09-01

We have analyzed Emx2 enhancers to determine how Emx2 functions during forebrain development are regulated. The FB (forebrain) enhancer we identified immediately 3' downstream of the last coding exon is well conserved among tetrapods and unexpectedly directed all the Emx2 expression in forebrain: caudal forebrain primordium at E8.5, dorsal telencephalon at E9.5-E10.5 and the cortical ventricular zone after E12.5. Otx, Tcf, Smad and two unknown transcription factor binding sites were essential to all these activities. The mutant that lacked this enhancer demonstrated that Emx2 expression under the enhancer is solely responsible for diencephalon development. However, in telencephalon, the FB enhancer did not have activities in cortical hem or Cajal-Retzius cells, nor was its activity in the cortex graded. Emx2 expression was greatly reduced, but persisted in the telencephalon of the enhancer mutant, indicating that there exists another enhancer for Emx2 expression unique to mammalian telencephalon.

Possible Involvement of Standardized Bacopa monniera Extract (CDRI-08) in Epigenetic Regulation of reelin and Brain-Derived Neurotrophic Factor to Enhance Memory

PubMed Central

Preethi, Jayakumar; Singh, Hemant K.; Rajan, Koilmani E.

2016-01-01

Bacopa monniera extract (CDRI-08; BME) has been known to improve learning and memory, and understanding the molecular mechanisms may help to know its specificity. We investigated whether the BME treatment alters the methylation status of reelin and brain-derived neurotropic factor (BDNF) to enhance the memory through the interaction of N-methyl-D-aspartate receptor (NMDAR) with synaptic proteins. Rat pups were subjected to novel object recognition test following daily oral administration of BME (80 mg/kg) in 0.5% gum acacia (per-orally, p.o.; PND 15–29)/three doses of 5-azacytidine (5-azaC; 3.2 mg/kg) in 0.9% saline (intraperitoneally, i.p.) on PND-30. After the behavioral test, methylation status of reelin, BDNF and activation of NMDAR, and its interactions with synaptic proteins were tested. Rat pups treated with BME/5-azaC showed higher discrimination towards novel objects than with old objects during testing. Further, we observed an elevated level of unmethylated DNA in reelin and BDNF promoter region. Up-regulated reelin along with the splice variant of apolipoprotein E receptor 2 (ApoER 2, ex 19) form a cluster and activate NMDAR through disabled adopter protein-1 (DAB1) to enhance BDNF. Observed results suggest that BME regulate reelin epigenetically, which might enhance NMDAR interactions with synaptic proteins and induction of BDNF. These changes may be linked with improved novel object recognition memory. PMID:27445807

Development of the Exercise Motives and Gains Inventory

ERIC Educational Resources Information Center

Strömmer, Sofia T.; Ingledew, David K.; Markland, David

2015-01-01

There are existing measures of exercise motives (what people want from exercise), but corresponding measures of gains (what people get) are needed, because motives and gains could influence each other and together influence other variables. An exercise motives and gains inventory (EMGI) was developed by creating gains scales to complement existing…

Sex-dependent role of vesicular glutamate transporter 3 in stress-regulation and related anxiety phenotype during the early postnatal period.

PubMed

Balázsfi, Diána; Farkas, Lívia; Csikota, Péter; Fodor, Anna; Zsebők, Sándor; Haller, József; Zelena, Dóra

2016-07-01

Stress and related disorders are in the focus of interest and glutamate is one of the most important neurotransmitters that can affect these processes. Glutamatergic neurons are characterized by vesicular glutamate transporters (VGluT1-3) among which vGluT3 is unique contributing to the non-canonical, neuromodulatory effect of glutamate. We aimed to study the role of vGluT3 in stress axis regulation and related anxiety during the early postnatal period using knockout (KO) mice with special focus on sex differences. Anxiety was explored on postnatal day (PND) 7-8 by maternal separation-induced ultrasonic vocalization (USV). Stress-hormone levels were detected 60 min after intraperitoneal lipopolysaccharide (LPS) injection 7 days later. Both genotypes gained weight, but on PND 14-15 KO mice pups had smaller body weight compared to wild type (WT). vGluT3 KO mice reacted to an immune stressor with enhanced adrenocorticotropin (ACTH) and corticosterone secretion compared to WT. Although there was a tendency for enhanced anxiety measured by more emitted USV, this did not reach the level of significance. The only sex-related effect was the enhanced corticosterone reactivity in male pups. For the HPA axis regulation in neonates vGluT3 expression seems to be dispensable under basal conditions, but is required for optimal response to immune stressors, most probably through an interaction with other neurotransmitters. Disturbance of the fine balance between these systems may result in a borderline enhanced anxiety-like behavior in vGluT3 KO pups.

Controlling slow and fast light and dynamic pulse-splitting with tunable optical gain in a whispering-gallery-mode microcavity

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

Asano, M.; Ikuta, R.; Imoto, N.

We report controllable manipulation of slow and fast light in a whispering-gallery-mode microtoroid resonator fabricated from Erbium (Er{sup 3+}) doped silica. We observe continuous transition of the coupling between the fiber-taper waveguide and the microresonator from undercoupling to critical coupling and then to overcoupling regimes by increasing the pump power even though the spatial distance between the resonator and the waveguide was kept fixed. This, in turn, enables switching from fast to slow light and vice versa just by increasing the optical gain. An enhancement of delay of two-fold over the passive silica resonator (no optical gain) was observed inmore » the slow light regime. Moreover, we show dynamic pulse splitting and its control in slow/fast light systems using optical gain.« less

Nicotine Replacement: Effects on Postcessation Weight Gain.

ERIC Educational Resources Information Center

Gross, Janet; And Others

1989-01-01

Examined nicotine replacement effects on postcessation weight gain in smoking cessation volunteers. Randomly assigned abstinent subjects to active nicotine or placebo gum conditions for 10 weeks. Analyses revealed strong evidence for gum effect on weight gain, with active gum users gaining mean total of 3.8 pounds compared with 7.8 pounds for…

ROS enhance angiogenic properties via regulation of NRF2 in tumor endothelial cells

PubMed Central

Towfik, Alam Mohammad; Akiyama, Kosuke; Ohga, Noritaka; Shindoh, Masanobu; Hida, Yasuhiro; Minowa, Kazuyuki; Fujisawa, Toshiaki; Hida, Kyoko

2017-01-01

Reactive oxygen species (ROS) are unstable molecules that activate oxidative stress. Because of the insufficient blood flow in tumors, the tumor microenvironment is often exposed to hypoxic condition and nutrient deprivation, which induces ROS accumulation. We isolated tumor endothelial cells (TECs) and found that they have various abnormalities, although the underlying mechanisms are not fully understood. Here we showed that ROS were accumulated in tumor blood vessels and ROS enhanced TEC migration with upregulation of several angiogenesis related gene expressions. It was also demonstrated that these genes were upregulated by regulation of Nuclear factor erythroid 2-related factor 2 (NRF2). Among these genes, we focused on Biglycan, a small leucine-rich proteoglycan. Inhibition of Toll-like receptors 2 and 4, known BIGLYCAN (BGN) receptors, cancelled the TEC motility stimulated by ROS. ROS inhibited NRF2 expression in TECs but not in NECs, and NRF2 inhibited phosphorylation of SMAD2/3, which activates transcription of BGN. These results indicated that ROS-induced BGN caused the pro-angiogenic phenotype in TECs via NRF2 dysregulation. PMID:28525375

Insulin detemir attenuates food intake, body weight gain and fat mass gain in diet-induced obese Sprague-Dawley rats.

PubMed

Rojas, J M; Printz, R L; Niswender, K D

2011-07-04

Initiation and intensification of insulin therapy commonly causes weight gain, a barrier to therapy. A contrasting body of evidence indicates that insulin functions as an adiposity negative feedback signal and reduces food intake, weight gain and adiposity via action in the central nervous system. Basal insulin analogs, detemir (Det) and glargine (Glar), have been associated with less hypoglycemia compared with neutral protamine hagedorn insulin, and Det with less weight gain, especially in patients with higher body mass index (BMI). We sought to determine whether insulin therapy per se causes body weight and fat mass gain when delivered via a clinically relevant subcutaneous (SC) route in the absence of hypoglycemia and glycosuria in non-diabetic lean and diet-induced obese rats. Rats were exposed to either a low-fat diet (LFD; 13.5% fat) or high-fat diet (HFD; 60% fat), and received Det (0.5 U kg(-1)), Glar (0.2 U kg(-1)) or vehicle (Veh) SC once daily for 4 weeks. These dosages of insulin were equipotent in rats with respect to blood-glucose concentration and did not induce hypoglycemia. As predicted by current models of energy homeostasis, neither insulin Det nor Glar therapy affected food intake and weight gain in LFD rats. Det treatment significantly attenuated food intake, body weight gain and fat mass gain relative to the Glar and Veh in high-fat fed animals, mirroring observations in humans. That neither insulin group gained excess weight, suggests weight gain with SC basal insulin therapy may not be inevitable. Our data further suggest that Det possesses a unique property to attenuate the development of obesity associated with a HFD.

Retinal Determination genes function along with cell-cell signals to regulate Drosophila eye development: examples of multi-layered regulation by Master Regulators

PubMed Central

Baker, Nicholas E.; Firth, Lucy C.

2015-01-01

It is thought that Retinal Determination gene products define the response made to cell-cell signals within the eye developmental field by binding to enhancers of genes that are also regulated by cell-cell signaling pathways. In Drosophila, Retinal Determination genes including Eyeless, teashirt, eyes absent, dachsous and sine oculis, are required for normal eye development and can induce ectopic eyes when mis-expressed. Characterization of the enhancers responsible for eye expression of the hedgehog, shaven, and atonal genes, as well as the dynamics of Retinal Determination gene expression themselves, now suggest a multilayered network whereby transcriptional regulation by either Retinal Determination genes or cell-cell signaling pathways can sometimes be indirect and mediated by other transcription factor intermediates. In this updated view of the interaction between extracellular information and cell intrinsic programs during development, regulation of individual genes might sometimes be several steps removed from either the Retinal Determination genes or cell-cell signaling pathways that nevertheless govern their expression. PMID:21607995

Enhanced cryopreservation of MSCs in microfluidic bioreactor by regulated shear flow

PubMed Central

Bissoyi, Akalabya; Bit, Arindam; Singh, Bikesh Kumar; Singh, Abhishek Kumar; Patra, Pradeep Kumar

2016-01-01

Cell-matrix systems can be stored for longer period of time by means of cryopreservation. Cell-matrix and cell-cell interaction has been found to be critical in a number of basic biological processes. Tissue structure maintenance, cell secretary activity, cellular migration, and cell-cell communication all exist because of the presence of cell interactions. This complex and co-ordinated interaction between cellular constituents, extracellular matrix and adjacent cells has been identified as a significant contributor in the overall co-ordination of tissue. The prime objective of this investigation is to evaluate the effects of shear-stress and cell-substrate interaction in successful recovery of adherent human mesenchymal-stem-cells (hMSCs). A customized microfluidic bioreactor has been used for the purpose. We have measured the changes in focal-point-adhesion (FPAs) by changing induced shear stress inside the bioreactor. The findings indicate that with increase in shear stress, FPAs increases between substrate and MSCs. Further, experimental results show that increased FPAs (4e-3 μbar) enhances the cellular survivability of adherent MSCs. Probably, for the first time involvement of focal point interaction in the outcome of cryopreservation of MSCs has been clarified, and it proved a potentially new approach for modification of cryopreservation protocol by up-regulating focal point of cells to improve its clinical application. PMID:27748463

A novel mammal-specific three partite enhancer element regulates node and notochord-specific Noto expression.

PubMed

Alten, Leonie; Schuster-Gossler, Karin; Eichenlaub, Michael P; Wittbrodt, Beate; Wittbrodt, Joachim; Gossler, Achim

2012-01-01

The vertebrate organizer and notochord have conserved, essential functions for embryonic development and patterning. The restricted expression of developmental regulators in these tissues is directed by specific cis-regulatory modules (CRMs) whose sequence conservation varies considerably. Some CRMs have been conserved throughout vertebrates and likely represent ancestral regulatory networks, while others have diverged beyond recognition but still function over a wide evolutionary range. Here we identify and characterize a mammalian-specific CRM required for node and notochord specific (NNC) expression of NOTO, a transcription factor essential for node morphogenesis, nodal cilia movement and establishment of laterality in mouse. A 523 bp enhancer region (NOCE) upstream the Noto promoter was necessary and sufficient for NNC expression from the endogenous Noto locus. Three subregions in NOCE together mediated full activity in vivo. Binding sites for known transcription factors in NOCE were functional in vitro but dispensable for NOCE activity in vivo. A FOXA2 site in combination with a novel motif was necessary for NOCE activity in vivo. Strikingly, syntenic regions in non-mammalian vertebrates showed no recognizable sequence similarities. In contrast to its activity in mouse NOCE did not drive NNC expression in transgenic fish. NOCE represents a novel, mammal-specific CRM required for the highly restricted Noto expression in the node and nascent notochord and thus regulates normal node development and function.

Above threshold spectral dependence of linewidth enhancement factor, optical duration and linear chirp of quantum dot lasers.

PubMed

Kim, Jimyung; Delfyett, Peter J

2009-12-07

The spectral dependence of the linewidth enhancement factor above threshold is experimentally observed from a quantum dot Fabry-Pérot semiconductor laser. The linewidth enhancement factor is found to be reduced when the quantum dot laser operates approximately 10 nm offset to either side of the gain peak. It becomes significantly reduced on the anti-Stokes side as compared to the Stokes side. It is also found that the temporal duration of the optical pulses generated from quantum dot mode-locked lasers is shorter when the laser operates away from the gain peak. In addition, less linear chirp is impressed on the pulse train generated from the anti-Stokes side whereas the pulses generated from the gain peak and Stokes side possess a large linear chirp. These experimental results imply that enhanced performance characteristics of quantum dot lasers can be achieved by operating on the anti-Stokes side, approximately 10 nm away from the gain peak.

Challenges for tree officers to enhance the provision of regulating ecosystem services from urban forests.

PubMed

Davies, Helen J; Doick, Kieron J; Hudson, Malcolm D; Schreckenberg, Kate