Neuronal medium that supports basic synaptic functions and activity of human neurons in vitro.

PubMed

Bardy, Cedric; van den Hurk, Mark; Eames, Tameji; Marchand, Cynthia; Hernandez, Ruben V; Kellogg, Mariko; Gorris, Mark; Galet, Ben; Palomares, Vanessa; Brown, Joshua; Bang, Anne G; Mertens, Jerome; Böhnke, Lena; Boyer, Leah; Simon, Suzanne; Gage, Fred H

2015-05-19

Human cell reprogramming technologies offer access to live human neurons from patients and provide a new alternative for modeling neurological disorders in vitro. Neural electrical activity is the essence of nervous system function in vivo. Therefore, we examined neuronal activity in media widely used to culture neurons. We found that classic basal media, as well as serum, impair action potential generation and synaptic communication. To overcome this problem, we designed a new neuronal medium (BrainPhys basal + serum-free supplements) in which we adjusted the concentrations of inorganic salts, neuroactive amino acids, and energetic substrates. We then tested that this medium adequately supports neuronal activity and survival of human neurons in culture. Long-term exposure to this physiological medium also improved the proportion of neurons that were synaptically active. The medium was designed to culture human neurons but also proved adequate for rodent neurons. The improvement in BrainPhys basal medium to support neurophysiological activity is an important step toward reducing the gap between brain physiological conditions in vivo and neuronal models in vitro.

Neuronal medium that supports basic synaptic functions and activity of human neurons in vitro

PubMed Central

Bardy, Cedric; van den Hurk, Mark; Eames, Tameji; Marchand, Cynthia; Hernandez, Ruben V.; Kellogg, Mariko; Gorris, Mark; Galet, Ben; Palomares, Vanessa; Brown, Joshua; Bang, Anne G.; Mertens, Jerome; Böhnke, Lena; Boyer, Leah; Simon, Suzanne; Gage, Fred H.

2015-01-01

Human cell reprogramming technologies offer access to live human neurons from patients and provide a new alternative for modeling neurological disorders in vitro. Neural electrical activity is the essence of nervous system function in vivo. Therefore, we examined neuronal activity in media widely used to culture neurons. We found that classic basal media, as well as serum, impair action potential generation and synaptic communication. To overcome this problem, we designed a new neuronal medium (BrainPhys basal + serum-free supplements) in which we adjusted the concentrations of inorganic salts, neuroactive amino acids, and energetic substrates. We then tested that this medium adequately supports neuronal activity and survival of human neurons in culture. Long-term exposure to this physiological medium also improved the proportion of neurons that were synaptically active. The medium was designed to culture human neurons but also proved adequate for rodent neurons. The improvement in BrainPhys basal medium to support neurophysiological activity is an important step toward reducing the gap between brain physiological conditions in vivo and neuronal models in vitro. PMID:25870293

Teaching and Demonstrating Classical Conditioning.

ERIC Educational Resources Information Center

Sparrow, John; Fernald, Peter

1989-01-01

Discusses classroom demonstrations of classical conditioning and notes tendencies to misrepresent Pavlov's procedures. Describes the design and construction of the conditioner that is used for demonstrating classical conditioning. Relates how students experience conditioning, generalization, extinction, discrimination, and spontaneous recovery.…

Defining level A IVIVC dissolution specifications based on individual in vitro dissolution profiles of a controlled release formulation.

PubMed

González-García, I; García-Arieta, A; Merino-Sanjuan, M; Mangas-Sanjuan, V; Bermejo, M

2018-07-01

Regulatory guidelines recommend that, when a level A IVIVC is established, dissolution specification should be established using averaged data and the maximum difference between AUC and C max between the reference and test formulations cannot be greater than 20%. However, averaging data assumes a loss of information and may reflect a bias in the results. The objective of the current work is to present a new approach to establish dissolution specifications using a new methodology (individual approach) instead of average data (classical approach). Different scenarios were established based on the relationship between in vitro-in vivo dissolution rate coefficient using a level A IVIVC of a controlled release formulation. Then, in order to compare this new approach with the classical one, six additional batches were simulated. For each batch, 1000 simulations of a dissolution assay were run. C max ratios between the reference formulation and each batch were calculated showing that the individual approach was more sensitive and able to detect differences between the reference and the batch formulation compared to the classical approach. Additionally, the new methodology displays wider dissolution specification limits than the classical approach, ensuring that any tablet from the new batch would generate in vivo profiles which its AUC or C max ratio will be out of the 0.8-1.25 range, taking into account the in vitro and in vivo variability of the new batches developed. Copyright © 2018 Elsevier B.V. All rights reserved.

In vitro model to evaluate reliability and accuracy of a dental shade-matching instrument.

PubMed

Kim-Pusateri, Seungyee; Brewer, Jane D; Dunford, Robert G; Wee, Alvin G

2007-11-01

There are several electronic shade-matching instruments available for clinical use; unfortunately, there are limited acceptable in vitro models to evaluate their reliability and accuracy. The purpose of this in vitro study was to evaluate the reliability and accuracy of a dental clinical shade-matching instrument. Using the shade-matching instrument (ShadeScan), color measurements were made of 3 commercial shade guides (VITA Classical, VITA 3D-Master, and Chromascop). Shade tabs were selected and placed in the middle of a gingival matrix (Shofu Gummy), with tabs of the same nominal shade from additional shade guides placed on both sides. Measurements were made of the central region of the shade tab inside a black box. For the reliability assessment, each shade tab from each of the 3 shade guide types was measured 10 times. For the accuracy assessment, each shade tab from 10 guides of each of the 3 types evaluated was measured once. Reliability, accuracy, and 95% confidence intervals were calculated for each shade tab. Differences were determined by 1-way ANOVA followed by the Bonferroni multiple comparison procedure. Reliability of ShadeScan was as follows: VITA Classical = 95.0%, VITA 3D-Master = 91.2%, and Chromascop = 76.5%. Accuracy of ShadeScan was as follows: VITA Classical = 65.0%, VITA 3D-Master = 54.2%, Chromascop = 84.5%. This in vitro study showed a varying degree of reliability and accuracy for ShadeScan, depending on the type of shade guide system used.

Expression of cholera toxin under non-AKI conditions in Vibrio cholerae El Tor induced by increasing the exposed surface of cultures.

PubMed

Sánchez, Joaquín; Medina, Gerardo; Buhse, Thomas; Holmgren, Jan; Soberón-Chavez, Gloria

2004-03-01

The regulatory systems controlling expression of the ctxAB genes encoding cholera toxin (CT) in the classical and El Tor biotypes of pathogenic Vibrio cholerae have been characterized and found to be almost identical. Notwithstanding this, special in vitro conditions, called AKI conditions, are required for El Tor bacteria to produce CT. The AKI conditions involve biphasic cultures. In phase 1 the organism is grown in a still tube for 4 h. In phase 2 the medium is poured into a flask to continue growth with shaking. Virtually no expression of CT occurs if this protocol is not followed. Here we demonstrated that CT expression takes place in single-phase still cultures if the volume-to-surface-area ratio is decreased, both under air and under an inert atmosphere. The expression of key genes involved in the regulation of CT production was analyzed, and we found that the expression pattern closely resembles the in vivo expression pattern.

Therapeutic Applications of Classic Hallucinogens.

PubMed

Bogenschutz, Michael P; Ross, Stephen

2018-01-01

This chapter reviews what is known about the therapeutic uses of the serotonergic or classic hallucinogens, i.e., psychoactive drugs such as LSD and psilocybin that exert their effects primarily through agonist activity at serotonin 2A (5HT2A) receptors. Following a review of the history of human use and scientific study of these drugs, the data from clinical research are summarized, including extensive work on the use of classic hallucinogens in the treatment of alcoholism and other addictions, studies of the use of LSD and psilocybin to relieve distress concerning death, particularly in patients with advanced or terminal cancer, and more limited data concerning the use of classic hallucinogens to treat mood and anxiety disorders. A survey of possible mechanisms of clinically relevant effects is provided. The well-established safety of classic hallucinogens is reviewed. To provide a clinical perspective, case summaries are provided of two individuals who received treatment in recent controlled trials of psilocybin: one being treated for alcoholism, the other suffering from anxiety and depression related to fear of death due to a cancer diagnosis. Although promising early phase research conducted from the 1950s through the early 1970s was discontinued before firm conclusions could be reached concerning the efficacy of any of the classic hallucinogens for any clinical condition, the research that was conducted in that era strongly suggests that classic hallucinogens have clinically relevant effects, particularly in the case of LSD treatment of alcoholism. In the past decade, clinical trials have resumed investigating the effects of classic hallucinogens in the treatment of existential distress in the face of cancer, and in the treatment of addictions including alcoholism and nicotine addiction. The studies that have been completed to date are not sufficient to establish efficacy, but the outcomes have been very encouraging, and larger trials, up to and including phase 3, are now underway or being planned. Although research has elucidated many of the acute neurobiological and psychological effects of classic hallucinogens on humans, animals, and in vitro systems, the mechanisms of clinically relevant persisting effects remain poorly understood.

A Classical Conditioning Procedure for the Hearing Assessment of Multiply Handicapped Persons.

ERIC Educational Resources Information Center

Lancioni, Giulio E.; And Others

1989-01-01

Hearing assessments of multiply handicapped children/adolescents were conducted using classical conditioning (with an air puff as unconditioned stimulus) and operant conditioning (with a modified visual reinforcement audiometry procedure or edible reinforcement). Findings indicate that classical conditioning was successful with 21 of the 23…

The Operant and the Classical in Conditioned Orientation of Drosophila melanogaster at the Flight Simulator

PubMed Central

Brembs, Björn; Heisenberg, Martin

2000-01-01

Ever since learning and memory have been studied experimentally, the relationship between operant and classical conditioning has been controversial. Operant conditioning is any form of conditioning that essentially depends on the animal's behavior. It relies on operant behavior. A motor output is called operant if it controls a sensory variable. The Drosophila flight simulator, in which the relevant behavior is a single motor variable (yaw torque), fully separates the operant and classical components of a complex conditioning task. In this paradigm a tethered fly learns, operantly or classically, to prefer and avoid certain flight orientations in relation to the surrounding panorama. Yaw torque is recorded and, in the operant mode, controls the panorama. Using a yoked control, we show that classical pattern learning necessitates more extensive training than operant pattern learning. We compare in detail the microstructure of yaw torque after classical and operant training but find no evidence for acquired behavioral traits after operant conditioning that might explain this difference. We therefore conclude that the operant behavior has a facilitating effect on the classical training. In addition, we show that an operantly learned stimulus is successfully transferred from the behavior of the training to a different behavior. This result unequivocally demonstrates that during operant conditioning classical associations can be formed. PMID:10753977

The operant and the classical in conditioned orientation of Drosophila melanogaster at the flight simulator.

PubMed

Brembs, B; Heisenberg, M

2000-01-01

Ever since learning and memory have been studied experimentally, the relationship between operant and classical conditioning has been controversial. Operant conditioning is any form of conditioning that essentially depends on the animal's behavior. It relies on operant behavior. A motor output is called operant if it controls a sensory variable. The Drosophila flight simulator, in which the relevant behavior is a single motor variable (yaw torque), fully separates the operant and classical components of a complex conditioning task. In this paradigm a tethered fly learns, operantly or classically, to prefer and avoid certain flight orientations in relation to the surrounding panorama. Yaw torque is recorded and, in the operant mode, controls the panorama. Using a yoked control, we show that classical pattern learning necessitates more extensive training than operant pattern learning. We compare in detail the microstructure of yaw torque after classical and operant training but find no evidence for acquired behavioral traits after operant conditioning that might explain this difference. We therefore conclude that the operant behavior has a facilitating effect on the classical training. In addition, we show that an operantly learned stimulus is successfully transferred from the behavior of the training to a different behavior. This result unequivocally demonstrates that during operant conditioning classical associations can be formed.

Quantum-correlation breaking channels, quantum conditional probability and Perron-Frobenius theory

NASA Astrophysics Data System (ADS)

Chruściński, Dariusz

2013-03-01

Using the quantum analog of conditional probability and classical Bayes theorem we discuss some aspects of particular entanglement breaking channels: quantum-classical and classical-classical channels. Applying the quantum analog of Perron-Frobenius theorem we generalize the recent result of Korbicz et al. (2012) [8] on full and spectrum broadcasting from quantum-classical channels to arbitrary quantum channels.

Genoprotective effect of the Chinese herbal decoction xiao jian zhong tang.

PubMed

Szeto, Yim-Tong; Cheng, Ngok-Fung; Pak, Sok-Cheon; Kalle, Wouter

2013-03-01

The Chinese herbal decoction formula Xiao Jian Zhong Tang (XJZT) is one of the classic formulas from the classic traditional Chinese medicine (TCM). Previous studies on XJZT found that it is effective for treating peptic ulcer, irritable bowel syndrome, functional gastroenteritis and similar psychosomatic disorders of the digestive organs. It has also been shown that all the herbs used in XJZT contain antioxidants. In this study, we investigated the in vitro DNA protection effect of the individual herb extracts and the whole formula. Water extract of the herbs and XJZT were used to pre-treat human lymphocytes. The lymphocytes were then exposed to hydrogen peroxide. The in vitro DNA protection effect of the herbs was investigated by comet assay. No DNA protective effect (P < 0.05) was found for individual herb extracts, but XJZT showed protection of human lymphocytic DNA upon oxidative stress (P < 0.05). The in vitro DNA protection effect of XJZT was conferred by the synergistic effect of the herbs, while the individual herbs had no such effect.

Classical swine fever virus replicated poorly in cells from MxA transgenic pigs.

PubMed

Zhao, Yicheng; Wang, Tiedong; Yao, Li; Liu, Bo; Teng, Chunbo; Ouyang, Hongsheng

2016-08-17

In addition to their value as livestock, pigs are susceptible to classical swine fever virus (CSFV) and can serve as reservoirs for CSFV, allowing it to develop into an epizootic. CSFV, a pestivirus of the Flaviviridae family, has a single-stranded RNA genome. Recent research has indicated that the human MxA protein inhibits the life cycles of certain RNA viruses, such as members of the Bunyaviridae family, the Flaviviridae family and others. To produce pigs with antiviral protection against CSFV, transgenic pigs expressing human MxA were generated by nuclear transplantation. Cells from three MxA transgenic piglets were used to investigate in vitro antiviral activity of MxA aganist CSFV, and the results of in vitro indirect immunofluorescence assays, virus titration and real-time PCR indicated that the MxA transgenic pig has an antiviral capacity against CSFV. Transgene with human MxA on pigs is feasible. High levels of MxA expression do inhibit CSFV in vitro at early time points post-infection at 60-96dpi.

Differential Transcriptional Response to Nonassociative and Associative Components of Classical Fear Conditioning in the Amygdala and Hippocampus

ERIC Educational Resources Information Center

Isiegas, Carolina; Stein, Joel; Hellman, Kevin; Hannenhalli, Sridhar; Abel, Ted; Keeley, Michael B.; Wood, Marcelo A.

2006-01-01

Classical fear conditioning requires the recognition of conditioned stimuli (CS) and the association of the CS with an aversive stimulus. We used Affymetrix oligonucleotide microarrays to characterize changes in gene expression compared to naive mice in both the amygdala and the hippocampus 30 min after classical fear conditioning and 30 min after…

Listening to classical music ameliorates unilateral neglect after stroke.

PubMed

Tsai, Pei-Luen; Chen, Mei-Ching; Huang, Yu-Ting; Lin, Keh-Chung; Chen, Kuan-Lin; Hsu, Yung-Wen

2013-01-01

OBJECTIVE. We determined whether listening to excerpts of classical music ameliorates unilateral neglect (UN) in stroke patients. METHOD. In this within-subject study, we recruited and separately tested 16 UN patients with a right-hemisphere stroke under three conditions within 1 wk. In each condition, participants were asked to complete three subtests of the Behavioral Inattention Test while listening to classical music, white noise, or nothing. All conditions and the presentation of the tests were counterbalanced across participants. Visual analog scales were used to provide self-reported ratings of arousal and mood. RESULTS. Participants generally had the highest scores under the classical music condition and the lowest scores under the silence condition. In addition, most participants rated their arousal as highest after listening to classical music. CONCLUSION. Listening to classical music may improve visual attention in stroke patients with UN. Future research with larger study populations is necessary to validate these findings. Copyright © 2013 by the American Occupational Therapy Association, Inc.

Long-term viability and differentiation of bovine oviductal monolayers: bidimensional versus three-dimensional culture.

PubMed

Gualtieri, R; Mollo, V; Braun, S; Barbato, V; Fiorentino, I; Talevi, R

2012-10-15

Different in vitro models have been developed to study the interaction of gametes and embryos with the maternal tract. In cattle, the interaction of the oviduct with gametes and embryos have been classically studied using oviductal explants or monolayers (OMs). Explants are well differentiated but have to be used within 24 h after collection, whereas OMs can be used for a longer time after cell confluence but dedifferentiate during culture, losing cell polarity and ciliation. Herein, OMs were cultured either in M199 plus 10% fetal calf serum or in a semidefined culture medium (Gray's medium), in an immersed condition on collagen-coated coated microporous polyester or polycarbonate inserts under air-liquid interface conditions. The influence of culture conditions on long-term viability and differentiation of OMs was evaluated through scanning electron microscopy, localization of centrin and tubulin at the confocal laser scanning microscope, and assessment of maintenance of viability of sperm bound to OMs. Findings demonstrated that OMs cultured in an immersed condition with Gray's medium retain a better morphology, do not exhibit signs of crisis at least until 3 wks postconfluence, and maintain the viability of bound sperm significantly better than parallel OMs cultured in M199 plus 10% fetal calf serum. OM culture with Gray's medium in air-liquid interface conditions on porous inserts promotes cell polarity, ciliation, and maintenance of bound sperm viability at least until 3 wks postconfluence. In conclusion, oviduct culture in Gray's medium in an immersed or air-liquid condition allows long-term culture and, in the latter case, also ciliation of bovine OMs, and may represent in vitro systems that mimick more closely the biological processes modulated by the oviduct in vivo. Copyright © 2012 Elsevier Inc. All rights reserved.

Development of a Perfusion Platform for Dynamic Cultivation of in vitro Skin Models.

PubMed

Strüver, Kay; Friess, Wolfgang; Hedtrich, Sarah

2017-01-01

Reconstructed skin models are suitable test systems for toxicity testing and for basic investigations on (patho-)physiological aspects of human skin. Reconstructed human skin, however, has clear limitations such as the lack of immune cells and a significantly weaker skin barrier function compared to native human skin. Potential reasons for the latter might be the lack of mechanical forces during skin model cultivation which is performed classically in static well-plate setups. Mechanical forces and shear stress have a major impact on tissue formation and, hence, tissue engineering. In the present work, a perfusion platform was developed allowing dynamic cultivation of in vitro skin models. The platform was designed to cultivate reconstructed skin at the air-liquid interface with a laminar and continuous medium flow below the dermis equivalent. Histological investigations confirmed the formation of a significantly thicker stratum corneum compared to the control cultivated under static conditions. Moreover, the skin differentiation markers involucrin and filaggrin as well as the tight junction proteins claudin 1 and occludin showed increased expression in the dynamically cultured skin models. Unexpectedly, despite improved differentiation, the skin barrier function of the dynamically cultivated skin models was not enhanced compared with the skin models cultivated under static conditions. © 2017 S. Karger AG, Basel.

Characterization of Vibrio cholerae O1 El Tor Biotype Variant Clinical Isolates from Bangladesh and Haiti, Including a Molecular Genetic Analysis of Virulence Genes ▿

PubMed Central

Son, Mike S.; Megli, Christina J.; Kovacikova, Gabriela; Qadri, Firdausi; Taylor, Ronald K.

2011-01-01

Vibrio cholerae serogroup O1, the causative agent of the diarrheal disease cholera, is divided into two biotypes: classical and El Tor. Both biotypes produce the major virulence factors toxin-coregulated pilus (TCP) and cholera toxin (CT). Although possessing genotypic and phenotypic differences, El Tor biotype strains displaying classical biotype traits have been reported and subsequently were dubbed El Tor variants. Of particular interest are reports of El Tor variants that produce various levels of CT, including levels typical of classical biotype strains. Here, we report the characterization of 10 clinical isolates from the International Centre for Diarrhoeal Disease Research, Bangladesh, and a representative strain from the 2010 Haiti cholera outbreak. We observed that all 11 strains produced increased CT (2- to 10-fold) compared to that of wild-type El Tor strains under in vitro inducing conditions, but they possessed various TcpA and ToxT expression profiles. Particularly, El Tor variant MQ1795, which produced the highest level of CT and very high levels of TcpA and ToxT, demonstrated hypervirulence compared to the virulence of El Tor wild-type strains in the infant mouse cholera model. Additional genotypic and phenotypic tests were conducted to characterize the variants, including an assessment of biotype-distinguishing characteristics. Notably, the sequencing of ctxB in some El Tor variants revealed two copies of classical ctxB, one per chromosome, contrary to previous reports that located ctxAB only on the large chromosome of El Tor biotype strains. PMID:21880975

Analysis and Synthesis of Adaptive Neural Elements and Assemblies

DTIC Science & Technology

1992-12-14

network, a learning rule (activity-dependent neuromodulation ), which has been proposed as a cellular mechanism for classical conditioning , was...activity-dependent neuromodulation ), which has been proposed as a cellular mechanism for classical conditioning, was demonstrated to support many...network, a learning rule (activity-dependent neuromodulation ), which has been proposed as a cellular mechanism for classical conditioning, was

Mangiferin inhibits macrophage classical activation via downregulating interferon regulatory factor 5 expression.

PubMed

Wei, Zhiquan; Yan, Li; Chen, Yixin; Bao, Chuanhong; Deng, Jing; Deng, Jiagang

2016-08-01

Mangiferin is a natural polyphenol and the predominant effective component of Mangifera indica Linn. leaves. For hundreds of years, Mangifera indica Linn. leaf has been used as an ingredient in numerous traditional Chinese medicine preparations for the treatment of bronchitis. However, the pharmacological mechanism of mangiferin in the treatment of bronchitis remains to be elucidated. Macrophage classical activation is important role in the process of bronchial airway inflammation, and interferon regulatory factor 5 (IRF5) has been identified as a key regulatory factor for macrophage classical activation. The present study used the THP‑1 human monocyte cell line to investigate whether mangiferin inhibits macrophage classical activation via suppressing IRF5 expression in vitro. THP‑1 cells were differentiated to macrophages by phorbol 12‑myristate 13‑acetate. Macrophages were polarized to M1 macrophages following stimulation with lipopolysaccharide (LPS)/interferon‑γ (IFN‑γ). Flow cytometric analysis was conducted to detect the M1 macrophages. Reverse transcription‑quantitative polymerase chain reaction was used to investigate cellular IRF5 gene expression. Levels of proinflammatory cytokines and IRF5 were assessed following cell culture and cellular homogenization using enzyme‑linked immunosorbent assay. IRF5 protein and nuclei co‑localization was performed in macrophages with laser scanning confocal microscope immunofluorescence analysis. The results of the present study demonstrated that mangiferin significantly inhibits LPS/IFN‑γ stimulation‑induced classical activation of macrophages in vitro and markedly decreases proinflammatory cytokine release. In addition, cellular IRF5 expression was markedly downregulated. These results suggest that the inhibitory effect of mangiferin on classical activation of macrophages may be exerted via downregulation of cellular IRF5 expression levels.

Mangiferin inhibits macrophage classical activation via downregulating interferon regulatory factor 5 expression

PubMed Central

Wei, Zhiquan; Yan, Li; Chen, Yixin; Bao, Chuanhong; Deng, Jing; Deng, Jiagang

2016-01-01

Mangiferin is a natural polyphenol and the predominant effective component of Mangifera indica Linn. leaves. For hundreds of years, Mangifera indica Linn. leaf has been used as an ingredient in numerous traditional Chinese medicine preparations for the treatment of bronchitis. However, the pharmacological mechanism of mangiferin in the treatment of bronchitis remains to be elucidated. Macrophage classical activation is important role in the process of bronchial airway inflammation, and interferon regulatory factor 5 (IRF5) has been identified as a key regulatory factor for macrophage classical activation. The present study used the THP-1 human monocyte cell line to investigate whether mangiferin inhibits macrophage classical activation via suppressing IRF5 expression in vitro. THP-1 cells were differentiated to macrophages by phorbol 12-myristate 13-acetate. Macrophages were polarized to M1 macrophages following stimulation with lipopolysaccharide (LPS)/interferon-γ (IFN-γ). Flow cytometric analysis was conducted to detect the M1 macrophages. Reverse transcription-quantitative polymerase chain reaction was used to investigate cellular IRF5 gene expression. Levels of proinflammatory cytokines and IRF5 were assessed following cell culture and cellular homogenization using enzyme-linked immunosorbent assay. IRF5 protein and nuclei co-localization was performed in macrophages with laser scanning confocal microscope immunofluorescence analysis. The results of the present study demonstrated that mangiferin significantly inhibits LPS/IFN-γ stimulation-induced classical activation of macrophages in vitro and markedly decreases proinflammatory cytokine release. In addition, cellular IRF5 expression was markedly downregulated. These results suggest that the inhibitory effect of mangiferin on classical activation of macrophages may be exerted via downregulation of cellular IRF5 expression levels. PMID:27277156

High-Throughput Screening for Human Galactokinase Inhibitors

PubMed Central

WIERENGA, KLAAS J.; LAI, KENT; BUCHWALD, PETER; TANG, MANSHU

2009-01-01

Inherited deficiency of galactose-1-phosphate uridyltransferase (GALT) can result in a potentially lethal disorder called classic galactosemia. Although the neonatal lethality associated with this disease can be prevented through early diagnosis and a galactose-restricted diet, the lack of effective therapy continues to have consequences: developmental delay, neurological disorders, and premature ovarian failure are common sequelae in childhood and adulthood. Several lines of evidence indicate that an elevated level of galactose-1-phosphate (gal-1-p), the product of galactokinase (GALK), is a major, if not sole, pathogenic mechanism in patients with classic galactosemia. The authors hypothesize that elimination of gal-1-p production by inhibiting GALK will relieve GALT-deficient cells from galactose toxicity. To test this hypothesis, they obtained human GALK using a bacterial expression system. They developed a robust, miniaturized, high-throughput GALK assay (Z′ factor =0.91) and used this assay to screen against libraries composed of 50,000 chemical compounds with diverse structural scaffolds. They selected 150 compounds that, at an average concentration of 33.3 μM, inhibited GALK activity in vitro more than 86.5% and with a reproducibility score of at least 0.7 for a confirmatory screen under identical experimental conditions. Of these 150 compounds, 34 were chosen for further characterization. Preliminary results indicated that these 34 compounds have potential to serve as leads to the development of more effective therapy of classic galactosemia. PMID:18490662

High-throughput screening for human galactokinase inhibitors.

PubMed

Wierenga, Klaas J; Lai, Kent; Buchwald, Peter; Tang, Manshu

2008-06-01

Inherited deficiency of galactose-1-phosphate uridyltransferase (GALT) can result in a potentially lethal disorder called classic galactosemia. Although the neonatal lethality associated with this disease can be prevented through early diagnosis and a galactose-restricted diet, the lack of effective therapy continues to have consequences: developmental delay, neurological disorders, and premature ovarian failure are common sequelae in childhood and adulthood. Several lines of evidence indicate that an elevated level of galactose-1-phosphate (gal-1-p), the product of galactokinase (GALK), is a major, if not sole, pathogenic mechanism in patients with classic galactosemia. The authors hypothesize that elimination of gal-1-p production by inhibiting GALK will relieve GALT-deficient cells from galactose toxicity. To test this hypothesis, they obtained human GALK using a bacterial expression system. They developed a robust, miniaturized, high-throughput GALK assay (Z' factor = 0.91) and used this assay to screen against libraries composed of 50,000 chemical compounds with diverse structural scaffolds. They selected 150 compounds that, at an average concentration of 33.3 microM, inhibited GALK activity in vitro more than 86.5% and with a reproducibility score of at least 0.7 for a confirmatory screen under identical experimental conditions. Of these 150 compounds, 34 were chosen for further characterization. Preliminary results indicated that these 34 compounds have potential to serve as leads to the development of more effective therapy of classic galactosemia.

Characterization of the Pivotal Carbon Metabolism of Streptococcus suis Serotype 2 under ex Vivo and Chemically Defined in Vitro Conditions by Isotopologue Profiling*

PubMed Central

Willenborg, Jörg; Huber, Claudia; Koczula, Anna; Lange, Birgit; Eisenreich, Wolfgang; Valentin-Weigand, Peter; Goethe, Ralph

2015-01-01

Streptococcus suis is a neglected zoonotic pathogen that has to adapt to the nutritional requirements in the different host niches encountered during infection and establishment of invasive diseases. To dissect the central metabolic activity of S. suis under different conditions of nutrient availability, we performed labeling experiments starting from [13C]glucose specimens and analyzed the resulting isotopologue patterns in amino acids of S. suis grown under in vitro and ex vivo conditions. In combination with classical growth experiments, we found that S. suis is auxotrophic for Arg, Gln/Glu, His, Leu, and Trp in chemically defined medium. De novo biosynthesis was shown for Ala, Asp, Ser, and Thr at high rates and for Gly, Lys, Phe, Tyr, and Val at moderate or low rates, respectively. Glucose degradation occurred mainly by glycolysis and to a minor extent by the pentose phosphate pathway. Furthermore, the exclusive formation of oxaloacetate by phosphoenolpyruvate (PEP) carboxylation became evident from the patterns in de novo synthesized amino acids. Labeling experiments with S. suis grown ex vivo in blood or cerebrospinal fluid reflected the metabolic adaptation to these host niches with different nutrient availability; however, similar key metabolic activities were identified under these conditions. This points at the robustness of the core metabolic pathways in S. suis during the infection process. The crucial role of PEP carboxylation for growth of S. suis in the host was supported by experiments with a PEP carboxylase-deficient mutant strain in blood and cerebrospinal fluid. PMID:25575595

P2Y12 expression and function in alternatively activated human microglia

PubMed Central

Ase, Ariel R.; Kinsara, Angham; Rao, Vijayaraghava T.S.; Michell-Robinson, Mackenzie; Leong, Soo Yuen; Butovsky, Oleg; Ludwin, Samuel K.; Séguéla, Philippe; Bar-Or, Amit; Antel, Jack P.

2015-01-01

Objective: To investigate and measure the functional significance of altered P2Y12 expression in the context of human microglia activation. Methods: We performed in vitro and in situ experiments to measure how P2Y12 expression can influence disease-relevant functional properties of classically activated (M1) and alternatively activated (M2) human microglia in the inflamed brain. Results: We demonstrated that compared to resting and classically activated (M1) human microglia, P2Y12 expression is increased under alternatively activated (M2) conditions. In response to ADP, the endogenous ligand of P2Y12, M2 microglia have increased ligand-mediated calcium responses, which are blocked by selective P2Y12 antagonism. P2Y12 antagonism was also shown to decrease migratory and inflammatory responses in human microglia upon exposure to nucleotides that are released during CNS injury; no effects were observed in human monocytes or macrophages. In situ experiments confirm that P2Y12 is selectively expressed on human microglia and elevated under neuropathologic conditions that promote Th2 responses, such as parasitic CNS infection. Conclusion: These findings provide insight into the roles of M2 microglia in the context of neuroinflammation and suggest a mechanism to selectively target a functionally unique population of myeloid cells in the CNS. PMID:25821842

Animal serum-free culture conditions for isolation and expansion of multipotent mesenchymal stromal cells from human BM.

PubMed

Müller, I; Kordowich, S; Holzwarth, C; Spano, C; Isensee, G; Staiber, A; Viebahn, S; Gieseke, F; Langer, H; Gawaz, M P; Horwitz, E M; Conte, P; Handgretinger, R; Dominici, M

2006-01-01

Multipotent mesenchymal stromal cells (MSC) have become important tools in regenerative and transplantation medicine. Rapidly increasing numbers of patients are receiving in vitro-expanded MSC. Culture conditions typically include FSC because human serum does not fully support growth of human MSC in vitro (MSC(FCS)). Concerns regarding BSE, other infectious complications and host immune reactions have fueled investigation of alternative culture supplements. As PDGF has long been identified as a growth factor for MSC, we tested media supplementation with platelet lysate for support of MSC proliferation. We found that primary cultures of BM-derived MSC can be established with animal serum-free media containing fresh frozen plasma and platelets (MSC(FFPP)). Moreover, MSC(FFPP) showed vigorous proliferation that was superior to classical culture conditions containing FCS. MSC(FFPP) morphology was equivalent to MSC(FCS), and MSC(FFPP) expressed CD73, CD90, CD105, CD106, CD146 and HLA-ABC while being negative for CD34, CD45 and surface HLA-DR, as expected. In addition to being phenotypically identical, MSC(FFPP) could efficiently differentiate into adipocytes and osteoblasts. In terms of immune regulatory properties, MSC(FFPP) were indistinguishable from MSC(FCS). Proliferation of PBMC induced by IL-2 in combination with OKT-3 or by PHA was inhibited in the presence of MSC(FFPP). Taken together, FCS can be replaced safely by FFPP in cultures of MSC for clinical purposes.

The novel iron chelator, 2-pyridylcarboxaldehyde 2-thiophenecarboxyl hydrazone, reduces catecholamine-mediated myocardial toxicity.

PubMed

Mladĕnka, Premysl; Kalinowski, Danuta S; Haskova, Pavlína; Bobrovová, Zuzana; Hrdina, Radomír; Simůnek, Tomás; Nachtigal, Petr; Semecký, Vladimĺr; Vávrová, Jaroslava; Holeckova, Magdaléna; Palicka, Vladimir; Mazurová, Yvona; Jansson, Patric J; Richardson, Des R

2009-01-01

Iron (Fe) chelators are used clinically for the treatment of Fe overload disease. Iron also plays a role in the pathology of many other conditions, and these potentially include the cardiotoxicity induced by catecholamines such as isoprenaline (ISO). The current study examined the potential of Fe chelators to prevent ISO cardiotoxicity. This was done as like other catecholamines, ISO contains the classical catechol moiety that binds Fe and may form redox-active and cytotoxic Fe complexes. Studies in vitro used the cardiomyocyte cell line, H9c2, which was treated with ISO in the presence or absence of the chelator, desferrioxamine (DFO), or the lipophilic ligand, 2-pyridylcarboxaldehyde 2-thiophenecarboxyl hydrazone (PCTH). Both of these chelators were not cardiotoxic and significantly reduced ISO cardiotoxicity in vitro. However, PCTH was far more effective than DFO, with the latter showing activity only at a high, clinically unachievable concentration. Further studies in vitro showed that interaction of ISO with Fe(II)/(III) did not increase cytotoxic radical generation, suggesting that this mechanism was not involved. Studies in vivo were initiated using rats pretreated intravenously with DFO or PCTH before subcutaneous administration of ISO (100 mg/kg). DFO at a clinically used dose (50 mg/kg) failed to reduce catecholamine cardiotoxicity, while PCTH at an equimolar dose totally prevented catecholamine-induced mortality and reduced cardiotoxicity. This study demonstrates that PCTH reduced ISO-induced cardiotoxicity in vitro and in vivo, demonstrating that Fe plays a role, in part, in the pathology observed.

Astrocyte - neuron lactate shuttle may boost more ATP supply to the neuron under hypoxic conditions - in silico study supported by in vitro expression data

PubMed Central

2011-01-01

Background Neuro-glial interactions are important for normal functioning of the brain as well as brain energy metabolism. There are two major working models - in the classical view, both neurons and astrocytes can utilize glucose as the energy source through oxidative metabolism, whereas in the astrocyte-neuron lactate shuttle hypothesis (ANLSH) it is the astrocyte which can consume glucose through anaerobic glycolysis to pyruvate and then to lactate, and this lactate is secreted to the extracellular space to be taken up by the neuron for further oxidative degradation. Results In this computational study, we have included hypoxia-induced genetic regulation of these enzymes and transporters, and analyzed whether the ANLSH model can provide an advantage to either cell type in terms of supplying the energy demand. We have based this module on our own experimental analysis of hypoxia-dependent regulation of transcription of key metabolic enzymes. Using this experimentation-supported in silico modeling, we show that under both normoxic and hypoxic conditions in a given time period ANLSH model does indeed provide the neuron with more ATP than in the classical view. Conclusions Although the ANLSH is energetically more favorable for the neuron, it is not the case for the astrocyte in the long term. Considering the fact that astrocytes are more resilient to hypoxia, we would propose that there is likely a switch between the two models, based on the energy demand of the neuron, so as to maintain the survival of the neuron under hypoxic or glucose-and-oxygen-deprived conditions. PMID:21995951

Astrocyte-neuron lactate shuttle may boost more ATP supply to the neuron under hypoxic conditions--in silico study supported by in vitro expression data.

PubMed

Genc, Seda; Kurnaz, Isil A; Ozilgen, Mustafa

2011-10-13

Neuro-glial interactions are important for normal functioning of the brain as well as brain energy metabolism. There are two major working models--in the classical view, both neurons and astrocytes can utilize glucose as the energy source through oxidative metabolism, whereas in the astrocyte-neuron lactate shuttle hypothesis (ANLSH) it is the astrocyte which can consume glucose through anaerobic glycolysis to pyruvate and then to lactate, and this lactate is secreted to the extracellular space to be taken up by the neuron for further oxidative degradation. In this computational study, we have included hypoxia-induced genetic regulation of these enzymes and transporters, and analyzed whether the ANLSH model can provide an advantage to either cell type in terms of supplying the energy demand. We have based this module on our own experimental analysis of hypoxia-dependent regulation of transcription of key metabolic enzymes. Using this experimentation-supported in silico modeling, we show that under both normoxic and hypoxic conditions in a given time period ANLSH model does indeed provide the neuron with more ATP than in the classical view. Although the ANLSH is energetically more favorable for the neuron, it is not the case for the astrocyte in the long term. Considering the fact that astrocytes are more resilient to hypoxia, we would propose that there is likely a switch between the two models, based on the energy demand of the neuron, so as to maintain the survival of the neuron under hypoxic or glucose-and-oxygen-deprived conditions.

Classical-Conditioning Demonstrations for Elementary and Advanced Courses.

ERIC Educational Resources Information Center

Abramson, Charles I.; And Others

1996-01-01

Describes two new exercises in classical conditioning that use earthworms and houseflies. The animals are available year-round and pose no risk to the students or instructor. The conditioned stimuli are odorants. These elicit a conditioned response of contraction in worms or proboscis extension in flies. (MJP)

Re'class'ification of 'quant'ified classical simulated annealing

NASA Astrophysics Data System (ADS)

Tanaka, Toshiyuki

2009-12-01

We discuss a classical reinterpretation of quantum-mechanics-based analysis of classical Markov chains with detailed balance, that is based on the quantum-classical correspondence. The classical reinterpretation is then used to demonstrate that it successfully reproduces a sufficient condition for cooling schedule in classical simulated annealing, which has the inverse-logarithmic scaling.

Role of Dendritic Cells in the Pathogenesis of Whipple's Disease

PubMed Central

Schinnerling, Katina; Geelhaar-Karsch, Anika; Allers, Kristina; Friebel, Julian; Conrad, Kristina; Loddenkemper, Christoph; Kühl, Anja A.; Erben, Ulrike; Ignatius, Ralf; Schneider, Thomas

2014-01-01

Accumulation of Tropheryma whipplei-stuffed macrophages in the duodenum, impaired T. whipplei-specific Th1 responses, and weak secretion of interleukin-12 (IL-12) are hallmarks of classical Whipple's disease (CWD). This study addresses dendritic cell (DC) functionality during CWD. We documented composition, distribution, and functionality of DC ex vivo or after in vitro maturation by fluorescence-activated cell sorting (FACS) and by immunohistochemistry in situ. A decrease in peripheral DC of untreated CWD patients compared to healthy donors was due to reduced CD11chigh myeloid DC (M-DC). Decreased maturation markers CD83, CD86, and CCR7, as well as low IL-12 production in response to stimulation, disclosed an immature M-DC phenotype. In vitro-generated monocyte-derived DC from CWD patients showed normal maturation and T cell-stimulatory capacity under proinflammatory conditions but produced less IL-12 and failed to activate T. whipplei-specific Th1 cells. In duodenal and lymphoid tissues, T. whipplei was found within immature DC-SIGN+ DC. DC and proliferating lymphocytes were reduced in lymph nodes of CWD patients compared to levels in controls. Our results indicate that dysfunctional IL-12 production by DC provides suboptimal conditions for priming of T. whipplei-specific T cells during CWD and that immature DC carrying T. whipplei contribute to the dissemination of the bacterium. PMID:25385798

Anticomplementary activity of horse IgG and F(ab')2 antivenoms.

PubMed

Squaiella-Baptistão, Carla Cristina; Marcelino, José Roberto; Ribeiro da Cunha, Luiz Eduardo; Gutiérrez, José María; Tambourgi, Denise V

2014-03-01

Envenomation by poisonous animals is a neglected condition according to the World Health Organization (WHO). Antivenoms are included in the WHO Essential Medicines List. It has been assumed that immunoglobulin G (IgG) antivenoms could activate the complement system through Fc and induce early adverse reactions (EARs). However, data in the literature indicate that F(ab')2 fragments can also activate the complement system. Herein, we show that several batches of IgG and F(ab')2 antivenoms from the Butantan, Vital Brazil, and Clodomiro Picado Institutes activated the complement classical pathway and induced the production of C3a; however, only those antivenoms from Clodomiro Picado generated C5a. Different protein profiles (IgG heavy chain, protein contaminants, and aggregates) were observed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and Western blot analyses. Our results show that various antivenoms from different producers are able to activate the classical pathway of the complement system and generate anaphylatoxins, and these findings suggest that factors, such as composition, contaminant proteins, and aggregates, may influence the anticomplementary activity of antivenoms in vitro. Therefore, there is a need to further improve antivenom production methods to reduce their anticomplementary activity and potential to cause EARs.

[Conditioning mechanisms and psychoneuroimmunology].

PubMed

Stockhorst, Ursula; Klosterhalfen, Sibylle

2005-01-01

This chapter deals with the role of conditioning principles in psychoneuroimmunology (PNI). We will first describe the paradigms of classical and instrumental conditioning and classify immune parameters that are subject to conditioning (chapter 1). So far, PNI research mainly uses classical (or Pavlovian) conditioning. We will summarize some of the paradigmatic studies, mainly animal studies (chapter 2) and also describe studies that support the clinical relevance of classical conditioning, i. e., in the pharmacological treatment of autoimmune diseases, transplantation and tumor chemotherapy (chapter 3). A study of our group on anticipatory immunomodulation in pediatric cancer patients is reported. Mechanisms mediating conditioned immunomodulation are summarized (chapter 4). We also describe studies that analyze the impact of instrumental conditioning contingencies on immune functioning (chapter 5). Finally, research perspectives are summarized (chapter 6).

Vitro culture of axe-head glochidia in pink heelsplitter Potamilus alatus and mechanism of its high host specialists

PubMed Central

Ma, Xue Yan; Zheng, Bing Qing; Xu, Pao; Xu, Liang; Hua, Dan; Yuan, Xin Hua; Gu, Ruo Bo

2018-01-01

The basal media M199 or MEM was utilized in the classical method of vitro culture of glochidia where 1–5% CO2 was required to maintain stable physiological pH for completion of non-parasitic metamorphosis. The classical method encounters a great challenge to those glochidia which undergo development of visceral tissue but significantly increase in size during metamorphosis. The improved in vitro culture techniques and classical methods were firstly compared for non-parasitic metamorphosis and development of glochidia in pink heelsplitter. Based on the improved method, the optimal vitro culture media was further selected from 14 plasmas or sera, realizing the non-parasitic metamorphosis of axe-head glochidia for the first time. The results showed that addition of different plasma (serum) had significant effect on glochidial metamorphosis in pink heelsplitter. Only glochidia in the skewband grunt and red drum groups could complete metamorphosis, the metamorphosis rate in skewband grunt was 93.3±3.1% at 24±0.5°C, significantly higher than in marine and desalinated red drum. Heat-inactivated treatment on the plasma of yellow catfish and Barbus capito had significant effect on glochidia survival and shell growth. The metamorphosis rate also varied among different gravid period, and generally decreased with gravid time. Further comparison of free amino acid and fatty acid indicated that the taurine of high concentration was the only amino acid that might promote the rapid growth of glochidial shell, and the lack of adequate DPA and DHA might be an important reason leading to the abnormal foot and visceral development. Combined with our results of artificial selection of host fish, we tentatively established the mechanism of its host specialists in pink heelsplitter for the first time. This is the first report on non-parasite metamorphosis of axe-head glochidia based on our improved vitro culture method, which should provide important reference to fundamental theory research of glochidia metamorphosis and also benefit for better understand of mechanism of host specialists and generalists of Unionidae species. PMID:29447194

Classical Conditioning of Eyelid and Mystacial Vibrissae Responses in Conscious Mice

ERIC Educational Resources Information Center

Delgado-Garcia, Jose Maria; Troncoso, Julieta; Munera, Alejandro

2004-01-01

The murine vibrissae sensorimotor system has been scrutinized as a target of motor learning through trace classical conditioning. Conditioned eyelid responses were acquired by using weak electrical whisker-pad stimulation as conditioned stimulus (CS) and strong electrical periorbital stimulation as unconditioned stimulus (US). In addition,…

Characterization of the pivotal carbon metabolism of Streptococcus suis serotype 2 under ex vivo and chemically defined in vitro conditions by isotopologue profiling.

PubMed

Willenborg, Jörg; Huber, Claudia; Koczula, Anna; Lange, Birgit; Eisenreich, Wolfgang; Valentin-Weigand, Peter; Goethe, Ralph

2015-02-27

Streptococcus suis is a neglected zoonotic pathogen that has to adapt to the nutritional requirements in the different host niches encountered during infection and establishment of invasive diseases. To dissect the central metabolic activity of S. suis under different conditions of nutrient availability, we performed labeling experiments starting from [(13)C]glucose specimens and analyzed the resulting isotopologue patterns in amino acids of S. suis grown under in vitro and ex vivo conditions. In combination with classical growth experiments, we found that S. suis is auxotrophic for Arg, Gln/Glu, His, Leu, and Trp in chemically defined medium. De novo biosynthesis was shown for Ala, Asp, Ser, and Thr at high rates and for Gly, Lys, Phe, Tyr, and Val at moderate or low rates, respectively. Glucose degradation occurred mainly by glycolysis and to a minor extent by the pentose phosphate pathway. Furthermore, the exclusive formation of oxaloacetate by phosphoenolpyruvate (PEP) carboxylation became evident from the patterns in de novo synthesized amino acids. Labeling experiments with S. suis grown ex vivo in blood or cerebrospinal fluid reflected the metabolic adaptation to these host niches with different nutrient availability; however, similar key metabolic activities were identified under these conditions. This points at the robustness of the core metabolic pathways in S. suis during the infection process. The crucial role of PEP carboxylation for growth of S. suis in the host was supported by experiments with a PEP carboxylase-deficient mutant strain in blood and cerebrospinal fluid. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

The mechanobiological aetiopathogenesis of tendinopathy: is it the over-stimulation or the under-stimulation of tendon cells?

PubMed Central

Arnoczky, Steven P; Lavagnino, Michael; Egerbacher, Monika

2007-01-01

While there is a significant amount of information available on the clinical presentation(s) and pathological changes associated with tendinopathy, the precise aetiopathogenesis of this condition remains a topic of debate. Classically, the aetiology of tendinopathy has been linked to the performance of repetitive activities (so-called overuse injuries). This has led many investigators to suggest that it is the mechanobiologic over-stimulation of tendon cells that is the initial stimulus for the degradative processes which have been shown to accompany tendinopathy. Although several studies have been able to demonstrate that the in vitro over-stimulation of tendon cells in monolayer can result in a pattern(s) of gene expression seen in clinical cases of tendinopathy, the strain magnitudes and durations used in these in vitro studies, as well as the model systems, may not be clinically relevant. Using a rat tail tendon model, we have studied the in vitro mechanobiologic response of tendon cells in situ to various tensile loading regimes. These studies have led to the hypothesis that the aetiopathogenic stimulus for the degenerative cascade which precedes the overt pathologic development of tendinopathy is the catabolic response of tendon cells to mechanobiologic under-stimulation as a result of microscopic damage to the collagen fibres of the tendon. In this review, we examine the rationale for this hypothesis and provide evidence in support of this theory. PMID:17696902

Sex differences in learning processes of classical and operant conditioning

PubMed Central

Dalla, Christina; Shors, Tracey J.

2009-01-01

Males and females learn and remember differently at different times in their lives. These differences occur in most species, from invertebrates to humans. We review here sex differences as they occur in laboratory rodent species. We focus on classical and operant conditioning paradigms, including classical eyeblink conditioning, fear conditioning, active avoidance and conditioned taste aversion. Sex differences have been reported during acquisition, retention and extinction in most of these paradigms. In general, females perform better than males in the classical eyeblink conditioning, in fear-potentiated startle and in most operant conditioning tasks, such as the active avoidance test. However, in the classical fear conditioning paradigm, in certain lever-pressing paradigms and in the conditioned taste aversion males outperform females or are more resistant to extinction. Most sex differences in conditioning are dependent on organizational effects of gonadal hormones during early development of the brain, in addition to modulation by activational effects during puberty and adulthood. Critically, sex differences in performance account for some of the reported effects on learning and these are discussed throughout the review. Because so many mental disorders are more prevalent on one sex than the other, it is important to consider sex differences in learning when applying animal models of learning for these disorders. Finally, we discuss how sex differences in learning continue to alter the brain throughout the lifespan. Thus, sex differences in learning are not only mediated by sex differences in the brain, but also contribute to them. PMID:19272397

Sex differences in learning processes of classical and operant conditioning.

PubMed

Dalla, Christina; Shors, Tracey J

2009-05-25

Males and females learn and remember differently at different times in their lives. These differences occur in most species, from invertebrates to humans. We review here sex differences as they occur in laboratory rodent species. We focus on classical and operant conditioning paradigms, including classical eyeblink conditioning, fear-conditioning, active avoidance and conditioned taste aversion. Sex differences have been reported during acquisition, retention and extinction in most of these paradigms. In general, females perform better than males in the classical eyeblink conditioning, in fear-potentiated startle and in most operant conditioning tasks, such as the active avoidance test. However, in the classical fear-conditioning paradigm, in certain lever-pressing paradigms and in the conditioned taste aversion, males outperform females or are more resistant to extinction. Most sex differences in conditioning are dependent on organizational effects of gonadal hormones during early development of the brain, in addition to modulation by activational effects during puberty and adulthood. Critically, sex differences in performance account for some of the reported effects on learning and these are discussed throughout the review. Because so many mental disorders are more prevalent in one sex than the other, it is important to consider sex differences in learning when applying animal models of learning for these disorders. Finally, we discuss how sex differences in learning continue to alter the brain throughout the lifespan. Thus, sex differences in learning are not only mediated by sex differences in the brain, but also contribute to them.

Handling of computational in vitro/in vivo correlation problems by Microsoft Excel: III. Convolution and deconvolution.

PubMed

Langenbucher, Frieder

2003-11-01

Convolution and deconvolution are the classical in-vitro-in-vivo correlation tools to describe the relationship between input and weighting/response in a linear system, where input represents the drug release in vitro, weighting/response any body response in vivo. While functional treatment, e.g. in terms of polyexponential or Weibull distribution, is more appropriate for general survey or prediction, numerical algorithms are useful for treating actual experimental data. Deconvolution is not considered an algorithm by its own, but the inversion of a corresponding convolution. MS Excel is shown to be a useful tool for all these applications.

A post-classical theory of enamel biomineralization… and why we need one.

PubMed

Simmer, James P; Richardson, Amelia S; Hu, Yuan-Yuan; Smith, Charles E; Ching-Chun Hu, Jan

2012-09-01

Enamel crystals are unique in shape, orientation and organization. They are hundreds of thousands times longer than they are wide, run parallel to each other, are oriented with respect to the ameloblast membrane at the mineralization front and are organized into rod or interrod enamel. The classical theory of amelogenesis postulates that extracellular matrix proteins shape crystallites by specifically inhibiting ion deposition on the crystal sides, orient them by binding multiple crystallites and establish higher levels of crystal organization. Elements of the classical theory are supported in principle by in vitro studies; however, the classical theory does not explain how enamel forms in vivo. In this review, we describe how amelogenesis is highly integrated with ameloblast cell activities and how the shape, orientation and organization of enamel mineral ribbons are established by a mineralization front apparatus along the secretory surface of the ameloblast cell membrane.

Associative Learning in Invertebrates

PubMed Central

Hawkins, Robert D.; Byrne, John H.

2015-01-01

This work reviews research on neural mechanisms of two types of associative learning in the marine mollusk Aplysia, classical conditioning of the gill- and siphon-withdrawal reflex and operant conditioning of feeding behavior. Basic classical conditioning is caused in part by activity-dependent facilitation at sensory neuron–motor neuron (SN–MN) synapses and involves a hybrid combination of activity-dependent presynaptic facilitation and Hebbian potentiation, which are coordinated by trans-synaptic signaling. Classical conditioning also shows several higher-order features, which might be explained by the known circuit connections in Aplysia. Operant conditioning is caused in part by a different type of mechanism, an intrinsic increase in excitability of an identified neuron in the central pattern generator (CPG) for feeding. However, for both classical and operant conditioning, adenylyl cyclase is a molecular site of convergence of the two signals that are associated. Learning in other invertebrate preparations also involves many of the same mechanisms, which may contribute to learning in vertebrates as well. PMID:25877219

Classical conditioning for preserving the effects of short melatonin treatment in children with delayed sleep: a pilot study.

PubMed

van Maanen, Annette; Meijer, Anne Marie; Smits, Marcel G; Oort, Frans J

2017-01-01

Melatonin treatment is effective in treating sleep onset problems in children with delayed melatonin onset, but effects usually disappear when treatment is discontinued. In this pilot study, we investigated whether classical conditioning might help in preserving treatment effects of melatonin in children with sleep onset problems, with and without comorbid attention deficit hyperactivity disorder (ADHD) or autism. After a baseline week, 16 children (mean age: 9.92 years, 31% ADHD/autism) received melatonin treatment for 3 weeks and then gradually discontinued the treatment. Classical conditioning was applied by having children drink organic lemonade while taking melatonin and by using a dim red light lamp that was turned on when children went to bed. Results were compared with a group of 41 children (mean age: 9.43 years, 34% ADHD/autism) who received melatonin without classical conditioning. Melatonin treatment was effective in advancing dim light melatonin onset and reducing sleep onset problems, and positive effects were found on health and behavior problems. After stopping melatonin, sleep returned to baseline levels. We found that for children without comorbidity in the experimental group, sleep latency and sleep start delayed less in the stop week, which suggests an effect of classical conditioning. However, classical conditioning seems counterproductive in children with ADHD or autism. Further research is needed to establish these results and to examine other ways to preserve melatonin treatment effects, for example, by applying morning light.

Comparison of Balance Performance Between Thai Classical Dancers and Non-Dancers.

PubMed

Krityakiarana, Warin; Jongkamonwiwat, Nopporn

2016-01-01

Thai classical dance is a traditional dramatic art, the technique of which has many features in common with South East Asian performing art. The choreographic patterns consist of various forms of balance control together with limb movements in slow rhythm. The grace and beauty of the dancer are dependent on how well the limb movements curve and angle. The relationship of whole body proportion and balance control in various patterns of support base is also important. The purpose of this study was to compare balance abilities between Thai classical dancers and non-dancers in different balance conditions. Twenty-five Thai classical dancers and 25 non-dancers performed the modified Sensory Organization Test (mSOT) and were further challenged by adding dynamic head tilts (DHTs) in four different directions during mSOT. Mixed model ANOVA was applied to determine the equilibrium score in each balance condition and also the interaction between dancer and non-dancer groups. It was found that Thai classical dancers achieved better equilibrium scores in all mSOT conditions except the least challenging one. Moreover, additional multitask conditions (mSOT+DHT) were revealed to profoundly affect differences between dancers and controls. In conclusion, Thai classical dancers demonstrated a better ability to maintain postural stability during different challenging postural tests. This information suggests various ways of putting the practice of Thai classical dance to use in the future.

Molecular mechanisms underlying formation of long-term reward memories and extinction memories in the honeybee (Apis mellifera)

PubMed Central

2014-01-01

The honeybee (Apis mellifera) has long served as an invertebrate model organism for reward learning and memory research. Its capacity for learning and memory formation is rooted in the ecological need to efficiently collect nectar and pollen during summer to ensure survival of the hive during winter. Foraging bees learn to associate a flower's characteristic features with a reward in a way that resembles olfactory appetitive classical conditioning, a learning paradigm that is used to study mechanisms underlying learning and memory formation in the honeybee. Due to a plethora of studies on appetitive classical conditioning and phenomena related to it, the honeybee is one of the best characterized invertebrate model organisms from a learning psychological point of view. Moreover, classical conditioning and associated behavioral phenomena are surprisingly similar in honeybees and vertebrates, suggesting a convergence of underlying neuronal processes, including the molecular mechanisms that contribute to them. Here I review current thinking on the molecular mechanisms underlying long-term memory (LTM) formation in honeybees following classical conditioning and extinction, demonstrating that an in-depth analysis of the molecular mechanisms of classical conditioning in honeybees might add to our understanding of associative learning in honeybees and vertebrates. PMID:25225299

Integrating classical and molecular approaches to evaluate the impact of nanosized zero-valent iron (nZVI) on soil organisms.

PubMed

Saccà, Maria Ludovica; Fajardo, Carmen; Costa, Gonzalo; Lobo, Carmen; Nande, Mar; Martin, Margarita

2014-06-01

Nanosized zero-valent iron (nZVI) is a new option for the remediation of contaminated soil and groundwater, but the effect of nZVI on soil biota is mostly unknown. In this work, nanotoxicological studies were performed in vitro and in two different standard soils to assess the effect of nZVI on autochthonous soil organisms by integrating classical and molecular analysis. Standardised ecotoxicity testing methods using Caenorhabditis elegans were applied in vitro and in soil experiments and changes in microbial biodiversity and biomarker gene expression were used to assess the responses of the microbial community to nZVI. The classical tests conducted in soil ruled out a toxic impact of nZVI on the soil nematode C. elegans in the test soils. The molecular analysis applied to soil microorganisms, however, revealed significant changes in the expression of the proposed biomarkers of exposure. These changes were related not only to the nZVI treatment but also to the soil characteristics, highlighting the importance of considering the soil matrix on a case by case basis. Furthermore, due to the temporal shift between transcriptional responses and the development of the corresponding phenotype, the molecular approach could anticipate adverse effects on environmental biota. Copyright © 2013 Elsevier Ltd. All rights reserved.

Unconscious classical conditioning of sexual arousal: evidence for the conditioning of female genital arousal to subliminally presented sexual stimuli.

PubMed

Both, Stephanie; Spiering, Mark; Laan, Ellen; Belcome, Sarah; van den Heuvel, Birre; Everaerd, Walter

2008-01-01

Although the assumption that sexual behavior is at least partly learned is common across theories of sexual behavior, classical conditioning of sexual response in women has been seldom studied. The study of unconscious classical conditioning of appetitive sexual responses in women. Vaginal pulse amplitude assessed by vaginal photoplethysmography, and ratings of sexual affective value. Pavlovian conditioning was examined in 18 sexually functional women by using two erotic pictures as conditional stimuli (CSs) and genital vibrotactile stimulation as unconditional stimulus (US). During the acquisition phase, the CSs were presented briefly (30 ms) and were masked by an immediately following masking stimulus. Only one CS (the CS+) was followed by the US during the acquisition phase. Conditioned responses were assessed during the extinction phase with supraliminal presentations of the CS+ and the CS-. Vaginal pulse amplitude was higher in response to the CS+ than during the CS- during the first extinction trial. There was no conditioning effect on ratings of affective value. The experiment demonstrates evidence for unconscious conditioning of genital responses in women, but no evidence for evaluative conditioning. The results add to the limited evidence for classical conditioning of sexual arousal in women, and to increasing evidence for associative emotional learning without awareness.

Making Classical Conditioning Understandable through a Demonstration Technique.

ERIC Educational Resources Information Center

Gibb, Gerald D.

1983-01-01

One lemon, an assortment of other fruits and vegetables, a tennis ball, and a Galvanic Skin Response meter are needed to implement this approach to teaching about classical conditioning in introductory psychology courses. (RM)

Pharmaceutical development and optimization of azithromycin suppository for paediatric use.

PubMed

Kauss, Tina; Gaubert, Alexandra; Boyer, Chantal; Ba, Boubakar B; Manse, Muriel; Massip, Stephane; Léger, Jean-Michel; Fawaz, Fawaz; Lembege, Martine; Boiron, Jean-Michel; Lafarge, Xavier; Lindegardh, Niklas; White, Nicholas J; Olliaro, Piero; Millet, Pascal; Gaudin, Karen

2013-01-30

Pharmaceutical development and manufacturing process optimization work was undertaken in order to propose a potential paediatric rectal formulation of azithromycin as an alternative to existing oral or injectable formulations. The target product profile was to be easy-to-use, cheap and stable in tropical conditions, with bioavailability comparable to oral forms, rapidly achieving and maintaining bactericidal concentrations. PEG solid solution suppositories were characterized in vitro using visual, HPLC, DSC, FTIR and XRD analyses. In vitro drug release and in vivo bioavailability were assessed; a study in rabbits compared the bioavailability of the optimized solid solution suppository to rectal solution and intra-venous product (as reference) and to the previous, non-optimized formulation (suspended azithromycin suppository). The bioavailability of azithromycin administered as solid solution suppositories relative to intra-venous was 43%, which compared well to the target of 38% (oral product in humans). The results of 3-month preliminary stability and feasibility studies were consistent with industrial production scale-up. This product has potential both as a classical antibiotic and as a product for use in severely ill children in rural areas. Industrial partners for further development are being sought. Copyright © 2012 Elsevier B.V. All rights reserved.

Pharmaceutical development and optimization of azithromycin suppository for paediatric use

PubMed Central

Kauss, Tina; Gaubert, Alexandra; Boyer, Chantal; Ba, Boubakar B.; Manse, Muriel; Massip, Stephane; Léger, Jean-Michel; Fawaz, Fawaz; Lembege, Martine; Boiron, Jean-Michel; Lafarge, Xavier; Lindegardh, Niklas; White, Nicholas J.; Olliaro, Piero; Millet, Pascal; Gaudin, Karen

2013-01-01

Pharmaceutical development and manufacturing process optimization work was undertaken in order to propose a potential paediatric rectal formulation of azithromycin as an alternative to existing oral or injectable formulations. The target product profile was to be easy-to-use, cheap and stable in tropical conditions, with bioavailability comparable to oral forms, rapidly achieving and maintaining bactericidal concentrations. PEG solid solution suppositories were characterized in vitro using visual, HPLC, DSC, FTIR and XRD analyses. In vitro drug release and in vivo bioavailability were assessed; a study in rabbits compared the bioavailability of the optimized solid solution suppository to rectal solution and intra-venous product (as reference) and to the previous, non-optimized formulation (suspended azithromycin suppository). The bioavailability of azithromycin administered as solid solution suppositories relative to intra-venous was 43%, which compared well to the target of 38% (oral product in humans). The results of 3-month preliminary stability and feasibility studies were consistent with industrial production scale-up. This product has potential both as a classical antibiotic and as a product for use in severely ill children in rural areas. Industrial partners for further development are being sought. PMID:23220079

Acute psychophysiological stress impairs human associative learning.

PubMed

Ehlers, M R; Todd, R M

2017-11-01

Addiction is increasingly discussed asa disorder of associative learning processes, with both operant and classical conditioning contributing to the development of maladaptive habits. Stress has long been known to promote drug taking and relapse and has further been shown to shift behavior from goal-directed actions towards more habitual ones. However, it remains to be investigated how acute stress may influence simple associative learning processes that occur before a habit can be established. In the present study, healthy young adults were exposed to either acute stress or a control condition half an hour before performing simple classical and operant conditioning tasks. Psychophysiological measures confirmed successful stress induction. Results of the operant conditioning task revealed reduced instrumental responding under delayed acute stress that resembled behavioral responses to lower levels of reward. The classical conditioning experiment revealed successful conditioning in both experimental groups; however, explicit knowledge of conditioning as indicated by stimulus ratings differentiated the stress and control groups. These findings suggest that operant and classical conditioning are differentially influenced by the delayed effects of acute stress with important implications for the understanding of how new habitual behaviors are initially established. Copyright © 2017 Elsevier Inc. All rights reserved.

Quantum Bohmian model for financial market

NASA Astrophysics Data System (ADS)

Choustova, Olga Al.

2007-01-01

We apply methods of quantum mechanics for mathematical modeling of price dynamics at the financial market. The Hamiltonian formalism on the price/price-change phase space describes the classical-like evolution of prices. This classical dynamics of prices is determined by “hard” conditions (natural resources, industrial production, services and so on). These conditions are mathematically described by the classical financial potential V(q), where q=(q1,…,qn) is the vector of prices of various shares. But the information exchange and market psychology play important (and sometimes determining) role in price dynamics. We propose to describe such behavioral financial factors by using the pilot wave (Bohmian) model of quantum mechanics. The theory of financial behavioral waves takes into account the market psychology. The real trajectories of prices are determined (through the financial analogue of the second Newton law) by two financial potentials: classical-like V(q) (“hard” market conditions) and quantum-like U(q) (behavioral market conditions).

Feeding Behavior of Aplysia: A Model System for Comparing Cellular Mechanisms of Classical and Operant Conditioning

ERIC Educational Resources Information Center

Baxter, Douglas A.; Byrne, John H.

2006-01-01

Feeding behavior of Aplysia provides an excellent model system for analyzing and comparing mechanisms underlying appetitive classical conditioning and reward operant conditioning. Behavioral protocols have been developed for both forms of associative learning, both of which increase the occurrence of biting following training. Because the neural…

Effect of indomethacin and lactoferrin on human tenocyte proliferation and collagen formation in vitro

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

Zhang, Yaonan; Department of Orthopaedic, Beijing Hospital of Ministry of Public Health, Beijing, China 100730; Wang, Xiao

Highlights: • Indomethacin, a classic NSAID, inhibited human tenocyte proliferation at high concentration (100 µM). • Lactoferrin at 50-100 µg/ml promoted human tenocyte survival, proliferation and collagen synthesis. • Lactoferrin is anabolic to human tenocytes in vitro and reverses potential inhibitory effects of NSAIDs on human tenocytes. - Abstract: Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used in patients with injuries and inflammation of tendon and ligament, and as post-surgical analgesics. The aim of this study is to investigate the effect of indomethacin, a classic NSAID and its combinational effect with an anabolic agent of skeletal tissue, lactoferrin, on the proliferationmore » and collagen formation of human tenocytes in vitro. A factorial experimental design was employed to study the dose-dependent effect of the combination of indomethacin and lactoferrin. The results showed that indomethacin at high concentration (100 μM) inhibited human tenocyte proliferation in culture medium with 1–10% fetal bovine serum (FBS) in vitro. Also, high dose of indomethacin inhibited the collagen formation of human tenocytes in 1% FBS culture medium. Lactoferrin at 50–100 μg/ml promoted human tenocyte survival in serum-free culture medium and enhanced proliferation and collagen synthesis of human tenocytes in 1% FBS culture medium. When 50–100 μg/ml lactoferrin was used in combination with 100–200 μM indomethacin, it partially rescued the inhibitory effects of indomethacin on human tenocyte proliferation, viability and collagen formation. To our knowledge, it is the first evidence that lactoferrin is anabolic to human tenocytes in vitro and reverses potential inhibitory effects of NSAIDs on human tenocytes.« less

Modelling in vivo creatine/phosphocreatine in vitro reveals divergent adaptations in human muscle mitochondrial respiratory control by ADP after acute and chronic exercise.

PubMed

Ydfors, Mia; Hughes, Meghan C; Laham, Robert; Schlattner, Uwe; Norrbom, Jessica; Perry, Christopher G R

2016-06-01

Mitochondrial respiratory sensitivity to ADP is thought to influence muscle fitness and is partly regulated by cytosolic-mitochondrial diffusion of ADP or phosphate shuttling via creatine/phosphocreatine (Cr/PCr) through mitochondrial creatine kinase (mtCK). Previous measurements of respiration in vitro with Cr (saturate mtCK) or without (ADP/ATP diffusion) show mixed responses of ADP sensitivity following acute exercise vs. less sensitivity after chronic exercise. In human muscle, modelling in vivo 'exercising' [Cr:PCr] during in vitro assessments revealed novel responses to exercise that differ from detections with or without Cr (±Cr). Acute exercise increased ADP sensitivity when measured without Cr but had no effect ±Cr or with +Cr:PCr, whereas chronic exercise increased sensitivity ±Cr but lowered sensitivity with +Cr:PCr despite increased markers of mitochondrial oxidative capacity. Controlling in vivo conditions during in vitro respiratory assessments reveals responses to exercise that differ from typical ±Cr comparisons and challenges our understanding of how exercise improves metabolic control in human muscle. Mitochondrial respiratory control by ADP (Kmapp ) is viewed as a critical regulator of muscle energy homeostasis. However, acute exercise increases, decreases or has no effect on Kmapp in human muscle, whereas chronic exercise surprisingly decreases sensitivity despite greater mitochondrial content. We hypothesized that modelling in vivo mitochondrial creatine kinase (mtCK)-dependent phosphate-shuttling conditions in vitro would reveal increased sensitivity (lower Kmapp ) after acute and chronic exercise. The Kmapp was determined in vitro with 20 mm Cr (+Cr), 0 mm Cr (-Cr) or 'in vivo exercising' 20 mm Cr/2.4 mm PCr (Cr:PCr) on vastus lateralis biopsies sampled from 11 men before, immediately after and 3 h after exercise on the first, fifth and ninth sessions over 3 weeks. Dynamic responses to acute exercise occurred throughout training, whereby the first session did not change Kmapp with in vivo Cr:PCr despite increases in -Cr. The fifth session decreased sensitivity with Cr:PCr or +Cr despite no change in -Cr. Chronic exercise increased sensitivity ±Cr in association with increased electron transport chain content (+33-62% complexes I-V), supporting classic proposals that link increased sensitivity to oxidative capacity. However, in vivo Cr:PCr reveals a perplexing decreased sensitivity, contrasting the increases seen ±Cr. Functional responses occurred without changes in fibre type or proteins regulating mitochondrial-cytosolic energy exchange (mtCK, VDAC and ANT). Despite the dynamic responses seen with ±Cr, modelling in vivo phosphate-shuttling conditions in vitro reveals that ADP sensitivity is unchanged after high-intensity exercise and is decreased after training. These findings challenge our understanding of how exercise regulates skeletal muscle energy homeostasis. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

Human umbilical cord stem cell conditioned medium versus serum-free culture medium in the treatment of cryopreserved human ovarian tissues in in-vitro culture: a randomized controlled trial.

PubMed

Jia, Yingxian; Shi, Xiaohan; Xie, Yidong; Xie, Xiaochuan; Wang, Yan; Li, Shangwei

2017-06-24

To reduce young female fertility loss, the in-vitro culture of cryopreserved ovarian cortical tissues (OCTs) is considered an effective approach without delaying treatment and undergoing stimulation medicine. However, ischemic damage and follicular loss during the in-vitro culture of OCTs are major technical challenges. Human umbilical cord stem cells (HUMSCs) and their conditioned medium (HUMSC-CM) have been considered to be potential resources for regeneration medicine because they secrete cytokines and enhance cell survival and function. The aim of this study was to determine whether HUMSC-CM improves the development of frozen-thawed in-vitro cultured ovarian tissues compared with a serum-free culture medium (SF-CM). The thawed OCTs (n = 68) were cultivated in HUMSC-CM and SF-CM in vitro for 8 days, and the ovarian tissues were processed and analyzed by a classical histological evaluation. The microvessel density (MVD) and apotosis detection during in-vitro culture of OCTs were also performed. A significant difference in the rate of morphologically normal primordial follicles in the HUMSC-CM group was observed compared to that in the SF-CM group (group C) from days 2 to 4 (day 2: group B 58.0 ± 2.45% vs group C 32.0 ± 5.83%, p = 0.002; day 3: group B 55.5 ± 4.20% vs group C 21.0 ± 9.80%, p = 0.048; day 4: group B 52.0 ± 4.08% vs group C 21.5 ± 8.19%, p = 0.019). The microvessel density (MVD) detection showed a time-dependent increase and peaked on day 4. There was a significant difference between groups B (49.33 ± 0.58) and C (24.33 ± 3.79) (p = 0.036). The percentage of apoptotic follicles in group B was lower than that in group C on day 1 (13.75 ± 2.50% vs 27.0 ± 10.10%, p = 0.003), day 5 (11.75 ± 1.50% vs 51.0 ± 10.5%, p = 0.019) and day 7 (15.0 ± 5.10% vs 46.5 ± 21.75%, p = 0.018). These data have provided the first experimental evidence of the effect of HUMSC-CM on frozen-thawed OCTs in vitro. The results showed that the HUMSC-CM group provided a better protecting effect on the in-vitro culture of the cryopreserved OCTs compared to the SF-CM group.

Genetically Modified Live Attenuated Leishmania donovani Parasites Induce Innate Immunity through Classical Activation of Macrophages That Direct the Th1 Response in Mice

PubMed Central

Bhattacharya, Parna; Dey, Ranadhir; Dagur, Pradeep K.; Kruhlak, Michael; Ismail, Nevien; Debrabant, Alain; Joshi, Amritanshu B.; Akue, Adovi; Kukuruga, Mark; Takeda, Kazuyo; Selvapandiyan, Angamuthu; McCoy, John Philip

2015-01-01

Visceral leishmaniasis (VL) causes significant mortality and there is no effective vaccine. Previously, we have shown that genetically modified Leishmania donovani parasites, here described as live attenuated parasites, induce a host protective adaptive immune response in various animal models. In this study, we demonstrate an innate immune response upon infection with live attenuated parasites in macrophages from BALB/c mice both in vitro and in vivo. In vitro infection of macrophages with live attenuated parasites (compared to that with wild-type [WT] L. donovani parasites) induced significantly higher production of proinflammatory cytokines (tumor necrosis factor alpha [TNF-α], interleukin-12 [IL-12], gamma interferon [IFN-γ], and IL-6), chemokines (monocyte chemoattractant protein 1/CCL-2, macrophage inflammatory protein 1α/CCL-3, and IP-10), reactive oxygen species (ROS), and nitric oxide, while concomitantly reducing anti-inflammatory cytokine IL-10 and arginase-1 activities, suggesting a dominant classically activated/M1 macrophage response. The classically activated response in turn helps in presenting antigen to T cells, as observed with robust CD4+ T cell activation in vitro. Similarly, parasitized splenic macrophages from live attenuated parasite-infected mice also demonstrated induction of an M1 macrophage phenotype, indicated by upregulation of IL-1β, TNF-α, IL-12, and inducible nitric oxide synthase 2 and downregulation of genes associated with the M2 phenotype, i.e., the IL-10, YM1, Arg-1, and MRC-1 genes, compared to WT L. donovani-infected mice. Furthermore, an ex vivo antigen presentation assay showed macrophages from live attenuated parasite-infected mice induced higher IFN-γ and IL-2 but significantly less IL-10 production by ovalbumin-specific CD4+ T cells, resulting in proliferation of Th1 cells. These data suggest that infection with live attenuated parasites promotes a state of classical activation (M1 dominant) in macrophages that leads to the generation of protective Th1 responses in BALB/c mice. PMID:26169275

Genetically Modified Live Attenuated Leishmania donovani Parasites Induce Innate Immunity through Classical Activation of Macrophages That Direct the Th1 Response in Mice.

PubMed

Bhattacharya, Parna; Dey, Ranadhir; Dagur, Pradeep K; Kruhlak, Michael; Ismail, Nevien; Debrabant, Alain; Joshi, Amritanshu B; Akue, Adovi; Kukuruga, Mark; Takeda, Kazuyo; Selvapandiyan, Angamuthu; McCoy, John Philip; Nakhasi, Hira L

2015-10-01

Visceral leishmaniasis (VL) causes significant mortality and there is no effective vaccine. Previously, we have shown that genetically modified Leishmania donovani parasites, here described as live attenuated parasites, induce a host protective adaptive immune response in various animal models. In this study, we demonstrate an innate immune response upon infection with live attenuated parasites in macrophages from BALB/c mice both in vitro and in vivo. In vitro infection of macrophages with live attenuated parasites (compared to that with wild-type [WT] L. donovani parasites) induced significantly higher production of proinflammatory cytokines (tumor necrosis factor alpha [TNF-α], interleukin-12 [IL-12], gamma interferon [IFN-γ], and IL-6), chemokines (monocyte chemoattractant protein 1/CCL-2, macrophage inflammatory protein 1α/CCL-3, and IP-10), reactive oxygen species (ROS), and nitric oxide, while concomitantly reducing anti-inflammatory cytokine IL-10 and arginase-1 activities, suggesting a dominant classically activated/M1 macrophage response. The classically activated response in turn helps in presenting antigen to T cells, as observed with robust CD4(+) T cell activation in vitro. Similarly, parasitized splenic macrophages from live attenuated parasite-infected mice also demonstrated induction of an M1 macrophage phenotype, indicated by upregulation of IL-1β, TNF-α, IL-12, and inducible nitric oxide synthase 2 and downregulation of genes associated with the M2 phenotype, i.e., the IL-10, YM1, Arg-1, and MRC-1 genes, compared to WT L. donovani-infected mice. Furthermore, an ex vivo antigen presentation assay showed macrophages from live attenuated parasite-infected mice induced higher IFN-γ and IL-2 but significantly less IL-10 production by ovalbumin-specific CD4(+) T cells, resulting in proliferation of Th1 cells. These data suggest that infection with live attenuated parasites promotes a state of classical activation (M1 dominant) in macrophages that leads to the generation of protective Th1 responses in BALB/c mice. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Sea Slugs, Subliminal Pictures, and Vegetative State Patients: Boundaries of Consciousness in Classical Conditioning

PubMed Central

Bekinschtein, Tristan A.; Peeters, Moos; Shalom, Diego; Sigman, Mariano

2011-01-01

Classical (trace) conditioning is a specific variant of associative learning in which a neutral stimulus leads to the subsequent prediction of an emotionally charged or noxious stimulus after a temporal gap. When conditioning is concurrent with a distraction task, only participants who can report the relationship (the contingency) between stimuli explicitly show associative learning. This suggests that consciousness is a prerequisite for trace conditioning. We review and question three main controversies concerning this view. Firstly, virtually all animals, even invertebrate sea slugs, show this type of learning; secondly, unconsciously perceived stimuli may elicit trace conditioning; and thirdly, some vegetative state patients show trace learning. We discuss and analyze these seemingly contradictory arguments to find the theoretical boundaries of consciousness in classical conditioning. We conclude that trace conditioning remains one of the best measures to test conscious processing in the absence of explicit reports. PMID:22164148

Cryptosporidium-contaminated water disinfection by a novel Fenton process.

PubMed

Matavos-Aramyan, Sina; Moussavi, Mohsen; Matavos-Aramyan, Hedieh; Roozkhosh, Sara

2017-05-01

Three novel modified advanced oxidation process systems including ascorbic acid-, pro-oxidants- and ascorbic acid-pro-oxidants-modified Fenton system were utilized to study the disinfection efficiency on Cryptosporidium-contaminated drinking water samples. Different concentrations of divalent and trivalent iron ions, hydrogen peroxide, ascorbic acid and pro-oxidants at different exposure times were investigated. These novel systems were also compared to the classic Fenton system and to the control system which comprised of only hydrogen peroxide. The complete in vitro mechanism of the mentioned modified Fenton systems are also provided. The results pointed out that by considering the optimal parameter limitations, the ascorbic acid-modified Fenton system decreased the Cryptosporidium oocytes viability to 3.91%, while the pro-oxidant-modified and ascorbic acid-pro-oxidant-modified Fenton system achieved an oocytes viability equal to 1.66% and 0%, respectively. The efficiency of the classic Fenton at optimal condition was observed to be 20.12% of oocytes viability. The control system achieved 86.14% of oocytes viability. The optimum values of the operational parameters during this study are found to be 80mgL -1 for the divalent iron, 30mgL -1 for ascorbic acid, 30mmol for hydrogen peroxide, 25mgL -1 for pro-oxidants and an exposure time equal to 5min. The ascorbic acid-pro-oxidants-modified Fenton system achieved a promising complete water disinfection (0% viability) at the optimal conditions, leaving this method a feasible process for water disinfection or decontamination, even at industrial scales. Copyright © 2017 Elsevier Inc. All rights reserved.

Roles of octopaminergic and dopaminergic neurons in appetitive and aversive memory recall in an insect.

PubMed

Mizunami, Makoto; Unoki, Sae; Mori, Yasuhiro; Hirashima, Daisuke; Hatano, Ai; Matsumoto, Yukihisa

2009-08-04

In insect classical conditioning, octopamine (the invertebrate counterpart of noradrenaline) or dopamine has been suggested to mediate reinforcing properties of appetitive or aversive unconditioned stimulus, respectively. However, the roles of octopaminergic and dopaminergic neurons in memory recall have remained unclear. We studied the roles of octopaminergic and dopaminergic neurons in appetitive and aversive memory recall in olfactory and visual conditioning in crickets. We found that pharmacological blockade of octopamine and dopamine receptors impaired aversive memory recall and appetitive memory recall, respectively, thereby suggesting that activation of octopaminergic and dopaminergic neurons and the resulting release of octopamine and dopamine are needed for appetitive and aversive memory recall, respectively. On the basis of this finding, we propose a new model in which it is assumed that two types of synaptic connections are formed by conditioning and are activated during memory recall, one type being connections from neurons representing conditioned stimulus to neurons inducing conditioned response and the other being connections from neurons representing conditioned stimulus to octopaminergic or dopaminergic neurons representing appetitive or aversive unconditioned stimulus, respectively. The former is called 'stimulus-response connection' and the latter is called 'stimulus-stimulus connection' by theorists studying classical conditioning in higher vertebrates. Our model predicts that pharmacological blockade of octopamine or dopamine receptors during the first stage of second-order conditioning does not impair second-order conditioning, because it impairs the formation of the stimulus-response connection but not the stimulus-stimulus connection. The results of our study with a cross-modal second-order conditioning were in full accordance with this prediction. We suggest that insect classical conditioning involves the formation of two kinds of memory traces, which match to stimulus-stimulus connection and stimulus-response connection. This is the first study to suggest that classical conditioning in insects involves, as does classical conditioning in higher vertebrates, the formation of stimulus-stimulus connection and its activation for memory recall, which are often called cognitive processes.

Porcine Mx1 Protein Inhibits Classical Swine Fever Virus Replication by Targeting Nonstructural Protein NS5B.

PubMed

Zhou, Jing; Chen, Jing; Zhang, Xiao-Min; Gao, Zhi-Can; Liu, Chun-Chun; Zhang, Yun-Na; Hou, Jin-Xiu; Li, Zhao-Yao; Kan, Lin; Li, Wen-Liang; Zhou, Bin

2018-04-01

Mx proteins are interferon (IFN)-induced GTPases that have broad antiviral activity against a wide range of RNA and DNA viruses; they belong to the dynamin superfamily of large GTPases. In this study, we confirmed the anti-classical swine fever virus (CSFV) activity of porcine Mx1 in vitro and showed that porcine Mx2 (poMx2), human MxA (huMxA), and mouse Mx1 (mmMx1) also have anti-CSFV activity in vitro Small interfering RNA (siRNA) experiments revealed that depletion of endogenous poMx1 or poMx2 enhanced CSFV replication, suggesting that porcine Mx proteins are responsible for the antiviral activity of interferon alpha (IFN-α) against CSFV infection. Confocal microscopy, immunoprecipitation, glutathione S -transferase (GST) pulldown, and bimolecular fluorescence complementation (BiFC) demonstrated that poMx1 associated with NS5B, the RNA-dependent RNA polymerase (RdRp) of CSFV. We used mutations in the poMx1 protein to elucidate the mechanism of their anti-CSFV activity and found that mutants that disrupted the association with NS5B lost all anti-CSV activity. Moreover, an RdRp activity assay further revealed that poMx1 undermined the RdRp activities of NS5B. Together, these results indicate that porcine Mx proteins exert their antiviral activity against CSFV by interacting with NS5B. IMPORTANCE Our previous studies have shown that porcine Mx1 (poMx1) inhibits classical swine fever virus (CSFV) replication in vitro and in vivo , but the molecular mechanism of action remains largely unknown. In this study, we dissect the molecular mechanism of porcine Mx1 and Mx2 against CSFV in vitro Our results show that poMx1 associates with NS5B, the RNA-dependent RNA polymerase of CSFV, resulting in the reduction of CSFV replication. Moreover, the mutants of poMx1 further elucidate the mechanism of their anti-CSFV activities. Copyright © 2018 American Society for Microbiology.

Stimulus Configuration, Classical Conditioning, and Hippocampal Function.

ERIC Educational Resources Information Center

Schmajuk, Nestor A.; DiCarlo, James J.

1991-01-01

The participation of the hippocampus in classical conditioning is described in terms of a multilayer network portraying stimulus configuration. A model of hippocampal function is presented, and computer simulations are used to study neural activity in the various brain areas mapped according to the model. (SLD)

Feeding behavior of Aplysia: a model system for comparing cellular mechanisms of classical and operant conditioning.

PubMed

Baxter, Douglas A; Byrne, John H

2006-01-01

Feeding behavior of Aplysia provides an excellent model system for analyzing and comparing mechanisms underlying appetitive classical conditioning and reward operant conditioning. Behavioral protocols have been developed for both forms of associative learning, both of which increase the occurrence of biting following training. Because the neural circuitry that mediates the behavior is well characterized and amenable to detailed cellular analyses, substantial progress has been made toward a comparative analysis of the cellular mechanisms underlying these two forms of associative learning. Both forms of associative learning use the same reinforcement pathway (the esophageal nerve, En) and the same reinforcement transmitter (dopamine, DA). In addition, at least one cellular locus of plasticity (cell B51) is modified by both forms of associative learning. However, the two forms of associative learning have opposite effects on B51. Classical conditioning decreases the excitability of B51, whereas operant conditioning increases the excitability of B51. Thus, the approach of using two forms of associative learning to modify a single behavior, which is mediated by an analytically tractable neural circuit, is revealing similarities and differences in the mechanisms that underlie classical and operant conditioning.

Scientific Formulas and Cognitive Economics, beyond "in Vitro" Entrepreneurship

ERIC Educational Resources Information Center

Maggioni, V.; Del Giudice, M.

2008-01-01

Cognitive economics is the fruit of intense "trans-epistemic" communication involving heterogeneous disciplinary areas: its most tangible application can be found in the dialogues between science and enterprise and in the relationship between cognition and entrepreneurship. The hypothesis of classical economics is that the academic inventor or…

Role of classical conditioning in learning gastrointestinal symptoms

PubMed Central

Stockhorst, Ursula; Enck, Paul; Klosterhalfen, Sibylle

2007-01-01

Nausea and/or vomiting are aversive gastrointestinal (GI) symptoms. Nausea and vomiting manifest unconditionally after a nauseogenic experience. However, there is correlative, quasiexperimental and experimental evidence that nausea and vomiting can also be learned via classical (Pavlovian) conditioning and might occur in anticipation of the nauseogenic event. Classical conditioning of nausea can develop with chemotherapy in cancer patients. Initially, nausea and vomiting occur during and after the administration of cytotoxic drugs (post-treatment nausea and vomiting) as unconditioned responses (UR). In addition, 20%-30% of cancer patients receiving chemotherapy report these side effects, despite antiemetic medication, when being re-exposed to the stimuli that usually signal the chemotherapy session and its drug infusion. These symptoms are called anticipatory nausea (AN) and/or anticipatory vomiting (ANV) and are explained by classical conditioning. Moreover, there is recent evidence for the assumption that post-chemotherapy nausea is at least partly influenced by learning. After summarizing the relevant assumptions of the conditioning model, revealing that a context can become a conditioned stimulus (CS), the present paper summarizes data that nausea and/or vomiting is acquired by classical conditioning and, consequently, may be alleviated by conditioning techniques. Our own research has focussed on two aspects and is emphasized here. First, a conditioned nausea model was established in healthy humans using body rotation as the nausea-inducing treatment. The validity of this motion-sickness model to examine conditioning mechanisms in the acquisition and alleviation of conditioned nausea and associated endocrine and immunological responses is summarized. Results from the rotation-induced motion sickness model showed that gender is an important moderator variable to be considered in further studies. This paper concludes with a review of the application of the demonstrated conditioning principles as interventions to ameliorate distressing AN/ANV in cancer patients undergoing chemotherapy, which is the second focus of our work. PMID:17659689

Role of classical conditioning in learning gastrointestinal symptoms.

PubMed

Stockhorst, Ursula; Enck, Paul; Klosterhalfen, Sibylle

2007-07-07

Nausea and/or vomiting are aversive gastrointestinal (GI) symptoms. Nausea and vomiting manifest unconditionally after a nauseogenic experience. However, there is correlative, quasiexperimental and experimental evidence that nausea and vomiting can also be learned via classical (Pavlovian) conditioning and might occur in anticipation of the nauseogenic event. Classical conditioning of nausea can develop with chemotherapy in cancer patients. Initially, nausea and vomiting occur during and after the administration of cytotoxic drugs (post-treatment nausea and vomiting) as unconditioned responses (UR). In addition, 20%-30% of cancer patients receiving chemotherapy report these side effects, despite antiemetic medication, when being re-exposed to the stimuli that usually signal the chemotherapy session and its drug infusion. These symptoms are called anticipatory nausea (AN) and/or anticipatory vomiting (ANV) and are explained by classical conditioning. Moreover, there is recent evidence for the assumption that post-chemotherapy nausea is at least partly influenced by learning. After summarizing the relevant assumptions of the conditioning model, revealing that a context can become a conditioned stimulus (CS), the present paper summarizes data that nausea and/or vomiting is acquired by classical conditioning and, consequently, may be alleviated by conditioning techniques. Our own research has focussed on two aspects and is emphasized here. First, a conditioned nausea model was established in healthy humans using body rotation as the nausea-inducing treatment. The validity of this motion-sickness model to examine conditioning mechanisms in the acquisition and alleviation of conditioned nausea and associated endocrine and immunological responses is summarized. Results from the rotation-induced motion sickness model showed that gender is an important moderator variable to be considered in further studies. This paper concludes with a review of the application of the demonstrated conditioning principles as interventions to ameliorate distressing AN/ANV in cancer patients undergoing chemotherapy, which is the second focus of our work.

Neural Correlates of Central Inhibition during Physical Fatigue

PubMed Central

Tanaka, Masaaki; Ishii, Akira; Watanabe, Yasuyoshi

2013-01-01

Central inhibition plays a pivotal role in determining physical performance during physical fatigue. Classical conditioning of central inhibition is believed to be associated with the pathophysiology of chronic fatigue. We tried to determine whether classical conditioning of central inhibition can really occur and to clarify the neural mechanisms of central inhibition related to classical conditioning during physical fatigue using magnetoencephalography (MEG). Eight right-handed volunteers participated in this study. We used metronome sounds as conditioned stimuli and maximum handgrip trials as unconditioned stimuli to cause central inhibition. Participants underwent MEG recording during imagery of maximum grips of the right hand guided by metronome sounds for 10 min. Thereafter, fatigue-inducing maximum handgrip trials were performed for 10 min; the metronome sounds were started 5 min after the beginning of the handgrip trials. The next day, neural activities during imagery of maximum grips of the right hand guided by metronome sounds were measured for 10 min. Levels of fatigue sensation and sympathetic nerve activity on the second day were significantly higher relative to those of the first day. Equivalent current dipoles (ECDs) in the posterior cingulated cortex (PCC), with latencies of approximately 460 ms, were observed in all the participants on the second day, although ECDs were not identified in any of the participants on the first day. We demonstrated that classical conditioning of central inhibition can occur and that the PCC is involved in the neural substrates of central inhibition related to classical conditioning during physical fatigue. PMID:23923034

GPR30, the non-classical membrane G protein related estrogen receptor, is overexpressed in human seminoma and promotes seminoma cell proliferation.

PubMed

Chevalier, Nicolas; Vega, Aurélie; Bouskine, Adil; Siddeek, Bénazir; Michiels, Jean-François; Chevallier, Daniel; Fénichel, Patrick

2012-01-01

Testicular germ cell tumours are the most frequent cancer of young men with an increasing incidence all over the world. Pathogenesis and reasons of this increase remain unknown but epidemiological and clinical data have suggested that fetal exposure to environmental endocrine disruptors (EEDs) with estrogenic effects, could participate to testicular germ cell carcinogenesis. However, these EEDs (like bisphenol A) are often weak ligands for classical nuclear estrogen receptors. Several research groups recently showed that the non classical membrane G-protein coupled estrogen receptor (GPER/GPR30) mediates the effects of estrogens and several xenoestrogens through rapid non genomic activation of signal transduction pathways in various human estrogen dependent cancer cells (breast, ovary, endometrium). The aim of this study was to demonstrate that GPER was overexpressed in testicular tumours and was able to trigger JKT-1 seminoma cell proliferation. We report here for the first time a complete morphological and functional characterization of GPER in normal and malignant human testicular germ cells. In normal adult human testes, GPER was expressed by somatic (Sertoli cells) and germ cells (spermatogonia and spermatocytes). GPER was exclusively overexpressed in seminomas, the most frequent testicular germ cell cancer, localized at the cell membrane and triggered a proliferative effect on JKT-1 cells in vitro, which was completely abolished by G15 (a GPER selective antagonist) and by siRNA invalidation. These results demonstrate that GPER is expressed by human normal adult testicular germ cells, specifically overexpressed in seminoma tumours and able to trigger seminoma cell proliferation in vitro. It should therefore be considered rather than classical ERs when xeno-estrogens or other endocrine disruptors are assessed in testicular germ cell cancers. It may also represent a prognosis marker and/or a therapeutic target for seminomas.

Fabry Disease in Families With Hypertrophic Cardiomyopathy: Clinical Manifestations in the Classic and Later-Onset Phenotypes.

PubMed

Adalsteinsdottir, Berglind; Palsson, Runolfur; Desnick, Robert J; Gardarsdottir, Marianna; Teekakirikul, Polakit; Maron, Martin; Appelbaum, Evan; Neisius, Ulf; Maron, Barry J; Burke, Michael A; Chen, Brenden; Pagant, Silvere; Madsen, Christoffer V; Danielsen, Ragnar; Arngrimsson, Reynir; Feldt-Rasmussen, Ulla; Seidman, Jonathan G; Seidman, Christine E; Gunnarsson, Gunnar Th

2017-08-01

The screening of Icelandic patients clinically diagnosed with hypertrophic cardiomyopathy resulted in identification of 8 individuals from 2 families with X-linked Fabry disease (FD) caused by GLA (α-galactosidase A gene) mutations encoding p.D322E (family A) or p.I232T (family B). Familial screening of at-risk relatives identified mutations in 16 family A members (8 men and 8 heterozygotes) and 25 family B members (10 men and 15 heterozygotes). Clinical assessments, α-galactosidase A (α-GalA) activities, glycosphingolipid substrate levels, and in vitro mutation expression were used to categorize p.D322E as a classic FD mutation and p.I232T as a later-onset FD mutation. In vitro expression revealed that p.D322E and p.I232T had α-GalA activities of 1.4% and 14.9% of the mean wild-type activity, respectively. Family A men had markedly decreased α-GalA activity and childhood-onset classic manifestations, except for angiokeratoma and cornea verticillata. Family B men had residual α-GalA activity and developed FD manifestations in adulthood. Despite these differences, all family A and family B men >30 years of age had left ventricular hypertrophy, which was mainly asymmetrical, and had similar late gadolinium enhancement patterns. Ischemic stroke and severe white matter lesions were more frequent among family A men, but neither family A nor family B men had overt renal disease. Family A and family B heterozygotes had less severe or no clinical manifestations. Men with classic or later-onset FD caused by GLA missense mutations developed prominent and similar cardiovascular disease at similar ages, despite markedly different α-GalA activities. © 2017 American Heart Association, Inc.

Generalized in vitro-in vivo relationship (IVIVR) model based on artificial neural networks

PubMed Central

Mendyk, Aleksander; Tuszyński, Paweł K; Polak, Sebastian; Jachowicz, Renata

2013-01-01

Background The aim of this study was to develop a generalized in vitro-in vivo relationship (IVIVR) model based on in vitro dissolution profiles together with quantitative and qualitative composition of dosage formulations as covariates. Such a model would be of substantial aid in the early stages of development of a pharmaceutical formulation, when no in vivo results are yet available and it is impossible to create a classical in vitro-in vivo correlation (IVIVC)/IVIVR. Methods Chemoinformatics software was used to compute the molecular descriptors of drug substances (ie, active pharmaceutical ingredients) and excipients. The data were collected from the literature. Artificial neural networks were used as the modeling tool. The training process was carried out using the 10-fold cross-validation technique. Results The database contained 93 formulations with 307 inputs initially, and was later limited to 28 in a course of sensitivity analysis. The four best models were introduced into the artificial neural network ensemble. Complete in vivo profiles were predicted accurately for 37.6% of the formulations. Conclusion It has been shown that artificial neural networks can be an effective predictive tool for constructing IVIVR in an integrated generalized model for various formulations. Because IVIVC/IVIVR is classically conducted for 2–4 formulations and with a single active pharmaceutical ingredient, the approach described here is unique in that it incorporates various active pharmaceutical ingredients and dosage forms into a single model. Thus, preliminary IVIVC/IVIVR can be available without in vivo data, which is impossible using current IVIVC/IVIVR procedures. PMID:23569360

Pavlovian conditioning of psychomotor stimulant-induced behaviours: has convenience led us astray?

PubMed

Martin-Iverson, M.T.; Fawcett, S.L.

1996-01-01

In order to classically condition the behavioural effects of psychomotor stimulants within a test context, rats were treated for 10 days with (+)-amphetamine (1.5mg/kg), (+)-4-propyl-9-hydroxynaphthoxazine (PHNO, 30µg/kg) or vehicle prior to a 1h placement into a test box. Conditioned behavioural effects were then measured in the previously drug-paired context after a vehicle injection (drug-free test day). Each rat was videotaped for the 1h test box exposure on days 1, 4, 7 and 10 of the drug conditioning trials, and on the drug-free test day. Eleven of 28 behaviours that were scored for frequency, duration and mean bout duration (bout length) were significantly influenced by at least one of the two drugs. Amphetamine predominantly increased bout lengths while PHNO predominantly increased bout frequency. Only two measures that were influenced by the drugs exhibited clear increases over controls in a manner consistent with a classical conditioning interpretation. Behavioural sensitization clearly occurred to some of the effects of amphetamine and PHNO, but these were not the same effects as those increased on the non-drug day testing for classical conditioning. Most behavioural effects of amphetamine and PHNO are not classically conditioned, and behavioural sensitization to these drugs, while perhaps context-specific, is not due to classical conditioning. Automated measures of behaviours have provided misleading evidence concerning the similarity among behavioural effects of stimulants, sensitization and effects of exposure to an environment previously paired with stimulants. Analysis of transitions between behaviours does not support the view that stimulants increase switching or response competition, or that behavioural reorganization is responsible for sensitization. Rather, it is suggested that stimulants selectively facilitate current stimulus-guided behaviours.

Treatment of raw and ozonated oil sands process-affected water under decoupled denitrifying anoxic and nitrifying aerobic conditions: a comparative study.

PubMed

Xue, Jinkai; Zhang, Yanyan; Liu, Yang; Gamal El-Din, Mohamed

2016-11-01

Batch experiments were performed to evaluate biodegradation of raw and ozonated oil sands process-affected water (OSPW) under denitrifying anoxic and nitrifying aerobic conditions for 33 days. The results showed both the anoxic and aerobic conditions are effective in degrading OSPW classical and oxidized naphthenic acids (NAs) with the aerobic conditions demonstrating higher removal efficiency. The reactors under nitrifying aerobic condition reduced the total classical NAs of raw OSPW by 69.1 %, with better efficiency for species of higher hydrophobicity. Compared with conventional aerobic reactor, nitrifying aerobic condition substantially shortened the NA degradation half-life to 16 days. The mild-dose ozonation remarkably accelerated the subsequent aerobic biodegradation of classical NAs within the first 14 days, especially for those with long carbon chains. Moreover, the ozone pretreatment enhanced the biological removal of OSPW classical NAs by leaving a considerably lower final residual concentration of 10.4 mg/L under anoxic conditions, and 5.7 mg/L under aerobic conditions. The combination of ozonation and nitrifying aerobic biodegradation removed total classical NAs by 76.5 % and total oxy-NAs (O3-O6) by 23.6 %. 454 Pyrosequencing revealed that microbial species capable of degrading recalcitrant hydrocarbons were dominant in all reactors. The most abundant genus in the raw and ozonated anoxic reactors was Thauera (~56 % in the raw OSPW anoxic reactor, and ~65 % in the ozonated OSPW anoxic reactor); whereas Rhodanobacter (~40 %) and Pseudomonas (~40 %) dominated the raw and ozonated aerobic reactors, respectively. Therefore, the combination of mild-dose ozone pretreatment and subsequent biological process could be a competent choice for OSPW treatment.

Classical conditioning in the treatment of psoriasis.

PubMed

Ader, R

2000-11-01

It has been argued that the placebo effect represents a learned response. Research is suggested to address the utility of applying principles derived from classical (Pavlovian) conditioning to the design of drug treatment protocols. In the present instance, it is hypothesized that, by capitalizing on conditioned pharmacotherapeutic responses, it may be possible to reduce the cumulative amount of corticosteroid medication used in the treatment of psoriasis.

Repeated Acquisitions and Extinctions in Classical Conditioning of the Rabbit Nictitating Membrane Response

ERIC Educational Resources Information Center

Kehoe, E. James

2006-01-01

The rabbit nictitating membrane (NM) response underwent successive stages of acquisition and extinction training in both delay (Experiment 1) and trace (Experiment 2) classical conditioning. In both cases, successive acquisitions became progressively faster, although the largest, most reliable acceleration occurred between the first and second…

Forward design of a complex enzyme cascade reaction

PubMed Central

Hold, Christoph; Billerbeck, Sonja; Panke, Sven

2016-01-01

Enzymatic reaction networks are unique in that one can operate a large number of reactions under the same set of conditions concomitantly in one pot, but the nonlinear kinetics of the enzymes and the resulting system complexity have so far defeated rational design processes for the construction of such complex cascade reactions. Here we demonstrate the forward design of an in vitro 10-membered system using enzymes from highly regulated biological processes such as glycolysis. For this, we adapt the characterization of the biochemical system to the needs of classical engineering systems theory: we combine online mass spectrometry and continuous system operation to apply standard system theory input functions and to use the detailed dynamic system responses to parameterize a model of sufficient quality for forward design. This allows the facile optimization of a 10-enzyme cascade reaction for fine chemical production purposes. PMID:27677244

Free Fermions and the Classical Compact Groups

NASA Astrophysics Data System (ADS)

Cunden, Fabio Deelan; Mezzadri, Francesco; O'Connell, Neil

2018-06-01

There is a close connection between the ground state of non-interacting fermions in a box with classical (absorbing, reflecting, and periodic) boundary conditions and the eigenvalue statistics of the classical compact groups. The associated determinantal point processes can be extended in two natural directions: (i) we consider the full family of admissible quantum boundary conditions (i.e., self-adjoint extensions) for the Laplacian on a bounded interval, and the corresponding projection correlation kernels; (ii) we construct the grand canonical extensions at finite temperature of the projection kernels, interpolating from Poisson to random matrix eigenvalue statistics. The scaling limits in the bulk and at the edges are studied in a unified framework, and the question of universality is addressed. Whether the finite temperature determinantal processes correspond to the eigenvalue statistics of some matrix models is, a priori, not obvious. We complete the picture by constructing a finite temperature extension of the Haar measure on the classical compact groups. The eigenvalue statistics of the resulting grand canonical matrix models (of random size) corresponds exactly to the grand canonical measure of free fermions with classical boundary conditions.

High-Density Lipoprotein Reduction Differentially Modulates to Classical and Nonclassical Monocyte Subpopulations in Metabolic Syndrome Patients and in LPS-Stimulated Primary Human Monocytes In Vitro

PubMed Central

Grün, Johanna L.; Manjarrez-Reyna, Aaron N.; Gómez-Arauz, Angélica Y.; Leon-Cabrera, Sonia; Bueno-Hernández, Nallely; Islas-Andrade, Sergio

2018-01-01

The effect of metabolic syndrome on human monocyte subpopulations has not yet been studied. Our main goal was to examine monocyte subpopulations in metabolic syndrome patients, while also identifying the risk factors that could directly influence these cells. Eighty-six subjects were divided into metabolic syndrome patients and controls. Monocyte subpopulations were quantified by flow cytometry, and interleukin- (IL-) 1β secretion levels were measured by ELISA. Primary human monocytes were cultured in low or elevated concentrations of high-density lipoprotein (HDL) and stimulated with lipopolysaccharide (LPS). The nonclassical monocyte (NCM) percentage was significantly increased in metabolic syndrome patients as compared to controls, whereas classical monocytes (CM) were reduced. Among all metabolic syndrome risk factors, HDL reduction exhibited the most important correlation with monocyte subpopulations and then was studied in vitro. Low HDL concentration reduced the CM percentage, whereas it increased the NCM percentage and IL-1β secretion in LPS-treated monocytes. The LPS effect was abolished when monocytes were cultured in elevated HDL concentrations. Concurring with in vitro results, IL-1β serum values significantly increased in metabolic syndrome patients with low HDL levels as compared to metabolic syndrome patients without HDL reduction. Our data demonstrate that HDL directly modulates monocyte subpopulations in metabolic syndrome. PMID:29850624

tRNA-derived short RNAs bind to Saccharomyces cerevisiae ribosomes in a stress-dependent manner and inhibit protein synthesis in vitro

PubMed Central

Kasprzyk, Marta; Twardowski, Tomasz

2016-01-01

Recently, a number of ribosome-associated non-coding RNAs (rancRNAs) have been discovered in all three domains of life. In our previous studies, we have described several types of rancRNAs in Saccharomyces cerevisiae, derived from many cellular RNAs, including mRNAs, rRNAs, tRNAs and snoRNAs. Here, we present the evidence that the tRNA fragments from simple eukaryotic organism S. cerevisiae directly bind to the ribosomes. Interestingly, rancRNA-tRFs in yeast are derived from both, 5′- and 3′-part of the tRNAs and both types of tRFs associate with the ribosomes in vitro. The location of tRFs within the ribosomes is distinct from classical A- and P-tRNA binding sites. Moreover, 3′-tRFs bind to the distinct site than 5′-tRFs. These interactions are stress dependent and as a consequence, provoke regulation of protein biosynthesis. We observe strong correlation between tRF binding to the ribosomes and inhibition of protein biosynthesis in particular environmental conditions. These results implicate the existence of an ancient and conserved mechanism of translation regulation with the involvement of ribosome-associating tRNA-derived fragments. PMID:27609601

Nonenzymatic glycation of guanosine 5'-triphosphate by glyceraldehyde: an in vitro study of AGE formation.

PubMed

Li, Yuyuan; Dutta, Udayan; Cohenford, Menashi A; Dain, Joel A

2007-12-01

Guanosine 5'-triphosphate (GTP) plays a significant role in the bioenergetics, metabolism, and signaling of cells; consequently, any modifications to the structure of the molecule can have profound effects on a cell's survival and function. Previous studies in our laboratory demonstrated that like proteins, purines, and pyrimidines can nonenzymatically react with sugars to generate advanced glycation endproducts (AGEs) and that these AGEs can form in vitro under physiological conditions. The objective of this investigation was twofold. First, it was to evaluate the susceptibility of ATP, GTP, CTP, and TTP to nonenzymatic modification by D-glucose and DL-glyceraldehyde, and second to assess the effect of various factors such as temperature, pH and incubation time, and sugar concentration on the rate and extent of nucleotide triphosphate AGE formation. Of the four nucleotide triphosphates that were studied, only GTP was significantly reactive forming a heterogeneous group of compounds with DL-glyceraldehyde. D-Glucose exhibited no significant reactivity with any of the nucleotide triphosphates, a finding that was supported by UV and fluorescence spectroscopy. Capillary electrophoresis, high-performance liquid chromatography and mass spectrometry allowed for a thorough analysis of the glycated GTP products and demonstrated that the modification of GTP by dl-glyceraldehyde occurred via the classical Amadori pathway.

Glutamate Decarboxylase-Dependent Acid Resistance in Brucella spp.: Distribution and Contribution to Fitness under Extremely Acidic Conditions

PubMed Central

Damiano, Maria Alessandra; Bastianelli, Daniela; Al Dahouk, Sascha; Köhler, Stephan; Cloeckaert, Axel

2014-01-01

Brucella is an expanding genus of major zoonotic pathogens, including at least 10 genetically very close species occupying a wide range of niches from soil to wildlife, livestock, and humans. Recently, we have shown that in the new species Brucella microti, the glutamate decarboxylase (Gad)-dependent system (GAD system) contributes to survival at a pH of 2.5 and also to infection in mice by the oral route. In order to study the functionality of the GAD system in the genus Brucella, 47 isolates, representative of all known species and strains of this genus, and 16 strains of the closest neighbor genus, Ochrobactrum, were studied using microbiological, biochemical, and genetic approaches. In agreement with the genome sequences, the GAD system of classical species was not functional, unlike that of most strains of Brucella ceti, Brucella pinnipedialis, and newly described species (B. microti, Brucella inopinata BO1, B. inopinata-like BO2, and Brucella sp. isolated from bullfrogs). In the presence of glutamate, these species were more acid resistant in vitro than classical terrestrial brucellae. Expression in trans of the gad locus from representative Brucella species in the Escherichia coli MG1655 mutant strain lacking the GAD system restored the acid-resistant phenotype. The highly conserved GAD system of the newly described or atypical Brucella species may play an important role in their adaptation to acidic external and host environments. Furthermore, the GAD phenotype was shown to be a useful diagnostic tool to distinguish these latter Brucella strains from Ochrobactrum and from classical terrestrial pathogenic Brucella species, which are GAD negative. PMID:25381237

Glutamate decarboxylase-dependent acid resistance in Brucella spp.: distribution and contribution to fitness under extremely acidic conditions.

PubMed

Damiano, Maria Alessandra; Bastianelli, Daniela; Al Dahouk, Sascha; Köhler, Stephan; Cloeckaert, Axel; De Biase, Daniela; Occhialini, Alessandra

2015-01-01

Brucella is an expanding genus of major zoonotic pathogens, including at least 10 genetically very close species occupying a wide range of niches from soil to wildlife, livestock, and humans. Recently, we have shown that in the new species Brucella microti, the glutamate decarboxylase (Gad)-dependent system (GAD system) contributes to survival at a pH of 2.5 and also to infection in mice by the oral route. In order to study the functionality of the GAD system in the genus Brucella, 47 isolates, representative of all known species and strains of this genus, and 16 strains of the closest neighbor genus, Ochrobactrum, were studied using microbiological, biochemical, and genetic approaches. In agreement with the genome sequences, the GAD system of classical species was not functional, unlike that of most strains of Brucella ceti, Brucella pinnipedialis, and newly described species (B. microti, Brucella inopinata BO1, B. inopinata-like BO2, and Brucella sp. isolated from bullfrogs). In the presence of glutamate, these species were more acid resistant in vitro than classical terrestrial brucellae. Expression in trans of the gad locus from representative Brucella species in the Escherichia coli MG1655 mutant strain lacking the GAD system restored the acid-resistant phenotype. The highly conserved GAD system of the newly described or atypical Brucella species may play an important role in their adaptation to acidic external and host environments. Furthermore, the GAD phenotype was shown to be a useful diagnostic tool to distinguish these latter Brucella strains from Ochrobactrum and from classical terrestrial pathogenic Brucella species, which are GAD negative. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Classical natural ovine scrapie prions are detected in practical volumes of blood by lamb and transgenic mouse bioassay

USDA-ARS?s Scientific Manuscript database

In vitro ligand-based immunoassay studies revealed abnormal isoforms of prion protein (PrP-Sc) are primarily associated with B lymphocytes of scrapie-infected sheep. Our recent study also demonstrated efficient transmission of scrapie to lambs following a transfusion of B lymphocytes isolated from 5...

Kinase Activity Studied in Living Cells Using an Immunoassay

ERIC Educational Resources Information Center

Bavec, Aljos?a

2014-01-01

This laboratory exercise demonstrates the use of an immunoassay for studying kinase enzyme activity in living cells. The advantage over the classical method, in which students have to isolate the enzyme from cell material and measure its activity in vitro, is that enzyme activity is modulated and measured in living cells, providing a more…

Evaluation of different fluoridated dentifrice formulations using an in situ erosion remineralization model.

PubMed

Barlow, A P; Sufi, F; Mason, S C

2009-01-01

The objective of these three clinical in situ studies was to investigate the relative performance of commercially available and experimental dentifrice formulations, having different fluoride sources and excipient ingredients, at remineralizing a bovine enamel surface previously softened by a dietary acid challenge. Each study utilized the same randomized, placebo-controlled, single-blind, crossover design. Subjects undertook single brushings of their natural teeth, with an in situ appliance in place, using different dentifrices in a randomly assigned order. Study A involved 58 subjects with the following dentifrices: Sensodyne Pronamel (1450 ppm F as NaF/5% KNO3); Blend-a-Med Classic (1450 ppm F as NaF); and a matched (Pronamel) placebo control (0 ppm F). Study B involved 56 subjects with the following dentifrices: Sensodyne Pronamel (1150 ppm F as NaF/5% KNO3); Crest Cavity Protection (1100 ppm F as NaF); Crest Pro-Health (0.454% SnF2 [1100 ppm F]/sodium hexametaphosphate); and a matched (Pronamel) placebo control (0 ppm F). Study C involved 56 subjects with the following dentifrices: Sensodyne Pronamel (1150 ppm F as NaF/5% KNO3); Sensodyne Pronamel Gentle Whitening (1150 ppm F as NaF/5% KNO3); Colgate Sensitive Multi Protection (1000 ppm F as NaMFP/5.53% potassium citrate/2% zinc citrate); and a matched (Pronamel) placebo control (0 ppm F). Subjects wore their palatal appliances holding eight bovine enamel blocks, previously exposed for 25 minutes to an in vitro erosive challenge with grapefruit juice, for the duration of the experiment. Five minutes after appliance insertion, subjects undertook a supervised, 90-second brush/rinse regimen with their assigned dentifrice. Surface microhardness (SMH) of the specimens was determined prior to the erosive challenge (baseline), after the in vitro erosive challenge, and were remeasured after four hours in situ remineralization following the tooth brushing event. Finally, SMH values were determined after a second in vitro erosive challenge at the end of the in situ remineralization period. Statistical analyses included ANOVA and pair-wise comparisons between treatments, testing at a 5% significance level. All three studies demonstrated significantly greater percent surface microhardness recovery (% SMHr) and percent relative erosion resistance (% RER) for dentifrices containing sodium fluoride compared to placebo controls. Overall, significantly greater % SMHr (p < 0.0001) was observed for Sensodyne Pronamel compared to Blend-a-Med Classic, Crest Pro-Health, and Colgate Sensitive Multi Protection dentifrices. Similarly, Sensodyne Pronamel delivered directionally better % RER vs. Blend-a-Med Classic (p = 0.0731), and significantly higher % RER vs. Crest Pro-Health (p = 0.0074) and Colgate Sensitive Multi Protection (p <0.0001). Crest Cavity Protection demonstrated significantly better % RER (p = 0.031) than Crest Pro-Health, which in turn demonstrated significantly better % RER than the placebo control (p < 0.0001). No other statistically significant between-product comparisons were observed. The results of these in situ studies support the effectiveness of dentifrices containing sodium fluoride to reharden enamel previously softened with an erosive challenge. Furthermore, these studies demonstrate the protective effects conferred to enamel, from erosion following the remineralization process in the presence of "ionic" fluoride. Under clinically relevant conditions, Sensodyne Pronamel and Sensodyne Pronamel Gentle Whitening offered superior anti-erosion performance compared to currently marketed dentifrice controls. These studies reinforce previous research indicating the importance of formulation effects on the relative remineralization performance of dentifrices under erosive conditions.

An in vitro study to evaluate the difference in shade between commercially available shade guides and glazed porcelain.

PubMed

Manimaran, P; Sadan, D Sai

2016-10-01

Smile is one of the most important interactive communication skills of a person. A smile is the key factor for an aesthetic appearance. Hence aesthetics is one of the motivating factor for the patients to seek dental care. Correction of unaesthetic appearance gives a positive effect to the self esteem of the patient. The aim of this study was to compare the difference in the shade between the commercially available shade guides namely Vita Classical And Ivoclar Chromascop and the fired porcelain samples fabricated using Vita Zahnfabrik VMK 95 and Ivoclar Classic Materials respectively. The objective of this study was to obtain a matching brand of material that has a particular shade tab among the brands used. To conclude, Ivoclar material matched the chromascop shade guide better than the vita material matched the vita classic shade guide.

Implicit and explicit learning in schizophrenics treated with olanzapine and with classic neuroleptics.

PubMed

Stevens, Andreas; Schwarz, Jürgen; Schwarz, Benedikt; Ruf, Ilona; Kolter, Thomas; Czekalla, Joerg

2002-03-01

Novel and classic neuroleptics differ in their effects on limbic striatal/nucleus accumbens (NA) and prefrontal cortex (PFC) dopamine turnover, suggesting differential effects on implicit and explicit learning as well as on anhedonia. The present study investigates whether such differences can be demonstrated in a naturalistic sample of schizophrenic patients. Twenty-five inpatients diagnosed with DSM-IV schizophrenic psychosis and treated for at least 14 days with the novel neuroleptic olanzapine were compared with 25 schizophrenics taking classic neuroleptics and with 25 healthy controls, matched by age and education level. PFC/NA-dependent implicit learning was assessed by a serial reaction time task (SRTT) and compared with cerebellum-mediated classical eye-blink conditioning and explicit visuospatial memory. Anhedonia was measured with the Snaith-Hamilton-Pleasure Scale (SHAPS). Implicit (SRTT) and psychomotor speed, but not explicit (visuospatial) learning were superior in the olanzapine-treated group as compared to the patients on classic neuroleptics. Compared to healthy controls, olanzapine-treated schizophrenics showed similar implicit learning, but reduced explicit (visuospatial) memory performance. Acquisition of eyeblink conditioning was not different between the three groups. There was no difference with regard to anhedonia and SANS scores between the patients. Olanzapine seems to interfere less with unattended learning and motor speed than classical neuroleptics. In daily life, this may translate into better adaptation to a rapidly changing environment. The effects seem specific, as in explicit learning and eyeblink conditioning no difference to classic NL was found.

A functional analysis of social reinforcement in vicarious verbal conditioning.

PubMed

Donohue, G B; Tryon, W W

1985-01-01

This article reports the results of 629 subjects in three experiments designed to replicate and extend the phenomenon of vicarious verbal conditioning. Experiment I replicated the finding that subjects who responded most to vicarious verbal conditioning were aware of the contingency involved. Experiment II attempted to examine the effects of prior history with the verbal reinforcer on vicarious verbal conditioning by providing seven groups of subjects with varying classic conditioning histories prior to vicarious verbal conditioning. The null results associated with this experiment were hypothesized to be due to the fact that the vicarious verbal conditioning took place in a language laboratory where the subjects could hear but not see the model. Experiment III replicated Experiment II in a live group context as was done in Experiment I. The results showed that vicarious verbal conditioning was again found to take place, that associating the verbal reinforcer with a tone or tone plus money via forward classic conditioning potentiated the effects of the verbal reinforcer, that backward classic conditioning did not potentiate the reinforcer, d) nor did either of two sensitization procedures potentiate the effects of the verbal reinforcer. Both aware and unaware subjects evidenced vicarious verbal conditioning.

In vitro dynamic model simulating the digestive tract of 6-month-old infants.

PubMed

Passannanti, Francesca; Nigro, Federica; Gallo, Marianna; Tornatore, Fabio; Frasso, Annalisa; Saccone, Giulia; Budelli, Andrea; Barone, Maria V; Nigro, Roberto

2017-01-01

In vivo assays cannot always be conducted because of ethical reasons, technical constraints or costs, but a better understanding of the digestive process, especially in infants, could be of great help in preventing food-related pathologies and in developing new formulas with health benefits. In this context, in vitro dynamic systems to simulate human digestion and, in particular, infant digestion could become increasingly valuable. To simulate the digestive process through the use of a dynamic model of the infant gastroenteric apparatus to study the digestibility of starch-based infant foods. Using M.I.D.A (Model of an Infant Digestive Apparatus), the oral, gastric and intestinal digestibility of two starch-based products were measured: 1) rice starch mixed with distilled water and treated using two different sterilization methods (the classical method with a holding temperature of 121°C for 37 min and the HTST method with a holding temperature of 137°C for 70 sec) and 2) a rice cream with (premium product) or without (basic product) an aliquot of rice flour fermented by Lactobacillus paracasei CBA L74. After the digestion the foods were analyzed for the starch concentration, the amount of D-glucose released and the percentage of hydrolyzed starch. An in vitro dynamic system, which was referred to as M.I.D.A., was obtained. Using this system, the starch digestion occurred only during the oral and intestinal phase, as expected. The D-glucose released during the intestinal phase was different between the classical and HTST methods (0.795 grams for the HTST versus 0.512 for the classical product). The same analysis was performed for the basic and premium products. In this case, the premium product had a significant difference in terms of the starch hydrolysis percentage during the entire process. The M.I.D.A. system was able to digest simple starches and a more complex food in the correct compartments. In this study, better digestibility of the premium product was revealed.

Semi-classical analysis and pseudo-spectra

NASA Astrophysics Data System (ADS)

Davies, E. B.

We prove an approximate spectral theorem for non-self-adjoint operators and investigate its applications to second-order differential operators in the semi-classical limit. This leads to the construction of a twisted FBI transform. We also investigate the connections between pseudo-spectra and boundary conditions in the semi-classical limit.

Overview of Classical Swine Fever (Hog Cholera, Classical Swine fever)

USDA-ARS?s Scientific Manuscript database

Classical swine fever is a contagious often fatal disease of pigs clinically characterized by high body temperature, lethargy, yellowish diarrhea, vomits and purple skin discoloration of ears, lower abdomen and legs. It was first described in the early 19th century in the USA. Later, a condition i...

Generalized Rainich conditions, generalized stress-energy conditions, and the Hawking-Ellis classification

NASA Astrophysics Data System (ADS)

Martín–Moruno, Prado; Visser, Matt

2017-11-01

The (generalized) Rainich conditions are algebraic conditions which are polynomial in the (mixed-component) stress-energy tensor. As such they are logically distinct from the usual classical energy conditions (NEC, WEC, SEC, DEC), and logically distinct from the usual Hawking-Ellis (Segré-Plebański) classification of stress-energy tensors (type I, type II, type III, type IV). There will of course be significant inter-connections between these classification schemes, which we explore in the current article. Overall, we shall argue that it is best to view the (generalized) Rainich conditions as a refinement of the classical energy conditions and the usual Hawking-Ellis classification.

The Global Error Assessment (GEA) model for the selection of differentially expressed genes in microarray data.

PubMed

Mansourian, Robert; Mutch, David M; Antille, Nicolas; Aubert, Jerome; Fogel, Paul; Le Goff, Jean-Marc; Moulin, Julie; Petrov, Anton; Rytz, Andreas; Voegel, Johannes J; Roberts, Matthew-Alan

2004-11-01

Microarray technology has become a powerful research tool in many fields of study; however, the cost of microarrays often results in the use of a low number of replicates (k). Under circumstances where k is low, it becomes difficult to perform standard statistical tests to extract the most biologically significant experimental results. Other more advanced statistical tests have been developed; however, their use and interpretation often remain difficult to implement in routine biological research. The present work outlines a method that achieves sufficient statistical power for selecting differentially expressed genes under conditions of low k, while remaining as an intuitive and computationally efficient procedure. The present study describes a Global Error Assessment (GEA) methodology to select differentially expressed genes in microarray datasets, and was developed using an in vitro experiment that compared control and interferon-gamma treated skin cells. In this experiment, up to nine replicates were used to confidently estimate error, thereby enabling methods of different statistical power to be compared. Gene expression results of a similar absolute expression are binned, so as to enable a highly accurate local estimate of the mean squared error within conditions. The model then relates variability of gene expression in each bin to absolute expression levels and uses this in a test derived from the classical ANOVA. The GEA selection method is compared with both the classical and permutational ANOVA tests, and demonstrates an increased stability, robustness and confidence in gene selection. A subset of the selected genes were validated by real-time reverse transcription-polymerase chain reaction (RT-PCR). All these results suggest that GEA methodology is (i) suitable for selection of differentially expressed genes in microarray data, (ii) intuitive and computationally efficient and (iii) especially advantageous under conditions of low k. The GEA code for R software is freely available upon request to authors.

Interest Inventory Items as Attitude Eliciting Stimuli in Classical Conditioning: A Test of the A-R-D Theory. Language, Personality, and Cross-Cultural Study and Measurement of the Human A-R-D (Motivational) System.

ERIC Educational Resources Information Center

Gross, Michael C.; Staats, Arthur W.

An experiment was conducted to test the hypothesis that interest inventory items elicit classically conditionable attitudinal responses. A higher-order conditioning procedure was used in which items from the Strong Vocational Interest Blank were employed as unconditioned stimuli and nonsense syllables as conditioned stimuli. Items for which the…

Mathematical modeling improves EC50 estimations from classical dose-response curves.

PubMed

Nyman, Elin; Lindgren, Isa; Lövfors, William; Lundengård, Karin; Cervin, Ida; Sjöström, Theresia Arbring; Altimiras, Jordi; Cedersund, Gunnar

2015-03-01

The β-adrenergic response is impaired in failing hearts. When studying β-adrenergic function in vitro, the half-maximal effective concentration (EC50 ) is an important measure of ligand response. We previously measured the in vitro contraction force response of chicken heart tissue to increasing concentrations of adrenaline, and observed a decreasing response at high concentrations. The classical interpretation of such data is to assume a maximal response before the decrease, and to fit a sigmoid curve to the remaining data to determine EC50 . Instead, we have applied a mathematical modeling approach to interpret the full dose-response curve in a new way. The developed model predicts a non-steady-state caused by a short resting time between increased concentrations of agonist, which affect the dose-response characterization. Therefore, an improved estimate of EC50 may be calculated using steady-state simulations of the model. The model-based estimation of EC50 is further refined using additional time-resolved data to decrease the uncertainty of the prediction. The resulting model-based EC50 (180-525 nm) is higher than the classically interpreted EC50 (46-191 nm). Mathematical modeling thus makes it possible to re-interpret previously obtained datasets, and to make accurate estimates of EC50 even when steady-state measurements are not experimentally feasible. The mathematical models described here have been submitted to the JWS Online Cellular Systems Modelling Database, and may be accessed at http://jjj.bio.vu.nl/database/nyman. © 2015 FEBS.

Two shikimate dehydrogenases, VvSDH3 and VvSDH4, are involved in gallic acid biosynthesis in grapevine.

PubMed

Bontpart, Thibaut; Marlin, Thérèse; Vialet, Sandrine; Guiraud, Jean-Luc; Pinasseau, Lucie; Meudec, Emmanuelle; Sommerer, Nicolas; Cheynier, Véronique; Terrier, Nancy

2016-05-01

In plants, the shikimate pathway provides aromatic amino acids that are used to generate numerous secondary metabolites, including phenolic compounds. In this pathway, shikimate dehydrogenases (SDH) 'classically' catalyse the reversible dehydrogenation of 3-dehydroshikimate to shikimate. The capacity of SDH to produce gallic acid from shikimate pathway metabolites has not been studied in depth. In grapevine berries, gallic acid mainly accumulates as galloylated flavan-3-ols. The four grapevine SDH proteins have been produced in Escherichia coli In vitro, VvSDH1 exhibited the highest 'classical' SDH activity. Two genes, VvSDH3 and VvSDH4, mainly expressed in immature berry tissues in which galloylated flavan-3-ols are accumulated, encoded enzymes with lower 'classical' activity but were able to produce gallic acid in vitro The over-expression of VvSDH3 in hairy-roots increased the content of aromatic amino acids and hydroxycinnamates, but had little or no effect on molecules more distant from the shikimate pathway (stilbenoids and flavan-3-ols). In parallel, the contents of gallic acid, β-glucogallin, and galloylated flavan-3-ols were increased, attesting to the influence of this gene on gallic acid metabolism. Phylogenetic analysis from dicotyledon SDHs opens the way for the examination of genes from other plants which accumulate gallic acid-based metabolites. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology.

In vitro studies of cutaneous retention of magnetic nanoemulsion loaded with zinc phthalocyanine for synergic use in skin cancer treatment

NASA Astrophysics Data System (ADS)

Primo, Fernando L.; Rodrigues, Marcilene M. A.; Simioni, Andreza R.; Bentley, Maria V. L. B.; Morais, Paulo C.; Tedesco, Antonio C.

In this study was developed a new nano drug delivery system (NDDS) based on association of biodegradable surfactants with biocompatible magnetic fluid of maguemita citrate derivative. This formulation consists in a magnetic emulsion with nanostructured colloidal particles. Preliminary in vitro experiments showed that the formulation presents a great potential for synergic application in the topical release of photosensitizer drug (PS) and excellent target tissue properties in the photodynamic therapy (PDT) combined with hyperthermia (HPT) protocols. The physical chemistry characterization and in vitro assays were carried out by Zn(II) Phtalocyanine (ZnPc) photosensitizer incorporated into NDDS in the absence and the presence of magnetic fluid, showed good results and high biocompatibility. In vitro experiments were accomplished by tape-stripping protocols for quantification of drug association with different skin tissue layers. This technique is a classical method for analyses of drug release in stratum corneum and epidermis+ dermis skin layers. The NDDS formulations were applied directly in pig skin (tissue model) fixed in the cell's Franz device with receptor medium container with a PBS/EtOH 20% solution (10 mM, pH 7.4) at 37 °C. After 12 h of topical administration stratum corneum was removed from fifty tapes and the ZnPc retained was evaluated by solvent extraction in dimetil-sulphoxide under ultrasonic bath. These results indicated that magnetic nanoemulsion (MNE) increase the drug release on the deeper skin layers when compared with classical formulation in the absence of magnetic particles. This could be related with the increase of biocompatibility of NDDS due to the great affinity for the polar extracelullar matrix in the skin and also for the increase in the drug partition inside of corneocites wall.

Cholinergic Septo-Hippocampal Innervation Is Required for Trace Eyeblink Classical Conditioning

ERIC Educational Resources Information Center

Fontan-Lozano, Angela; Troncoso, Julieta; Munera, Alejandro; Carrion, Angel Manuel; Delgado-Garcia, Jose Maria

2005-01-01

We studied the effects of a selective lesion in rats, with 192-IgG-saporin, of the cholinergic neurons located in the medial septum/diagonal band (MSDB) complex on the acquisition of classical and instrumental conditioning paradigms. The MSDB lesion induced a marked deficit in the acquisition, but not in the retrieval, of eyeblink classical…

2010 Workplace and Gender Relations Survey of Active Duty Members. Tabulations of Responses

DTIC Science & Technology

2011-04-01

Sexual Coercion can be defined as classic quid pro quo , instances of special treatment or favoritism conditional...defined as classic quid pro quo , instances of special treatment or favoritism conditional on sexual cooperation. Percentages Percent Responding...marked as happening to you, do you consider to have been sexual harassment ? ........................................... 342 31. Sexual Harassment

Quantum-classical correspondence in the vicinity of periodic orbits

NASA Astrophysics Data System (ADS)

Kumari, Meenu; Ghose, Shohini

2018-05-01

Quantum-classical correspondence in chaotic systems is a long-standing problem. We describe a method to quantify Bohr's correspondence principle and calculate the size of quantum numbers for which we can expect to observe quantum-classical correspondence near periodic orbits of Floquet systems. Our method shows how the stability of classical periodic orbits affects quantum dynamics. We demonstrate our method by analyzing quantum-classical correspondence in the quantum kicked top (QKT), which exhibits both regular and chaotic behavior. We use our correspondence conditions to identify signatures of classical bifurcations even in a deep quantum regime. Our method can be used to explain the breakdown of quantum-classical correspondence in chaotic systems.

Improved efficiency of plant regeneration from protoplasts of eggplant Solanum melongena L.

PubMed

Guri, A; Izhar, S

1984-12-01

Eggplant (Solanum melongena L.) mesophyll protoplasts were obtained from in vitro growing plants of line 410 and cv. 'Classic'. Relatively high (15%) plating efficiency was achieved using petri dishes with alternate quadrants containing reservoir medium (R medium + 1% activated charcoal) and culture medium. Shoot regeneration occurred within 6 weeks following initiation of protoplast culture.

KNOX1 is expressed and epigenetically regulated during in vitro conditions in Agave spp

PubMed Central

2012-01-01

Background The micropropagation is a powerful tool to scale up plants of economical and agronomical importance, enhancing crop productivity. However, a small but growing body of evidence suggests that epigenetic mechanisms, such as DNA methylation and histone modifications, can be affected under the in vitro conditions characteristic of micropropagation. Here, we tested whether the adaptation to different in vitro systems (Magenta boxes and Bioreactors) modified epigenetically different clones of Agave fourcroydes and A. angustifolia. Furthermore, we assessed whether these epigenetic changes affect the regulatory expression of KNOTTED1-like HOMEOBOX (KNOX) transcription factors. Results To gain a better understanding of epigenetic changes during in vitro and ex vitro conditions in Agave fourcroydes and A. angustifolia, we analyzed global DNA methylation, as well as different histone modification marks, in two different systems: semisolid in Magenta boxes (M) and temporary immersion in modular Bioreactors (B). No significant difference was found in DNA methylation in A. fourcroydes grown in either M or B. However, when A. fourcroydes was compared with A. angustifolia, there was a two-fold difference in DNA methylation between the species, independent of the in vitro system used. Furthermore, we detected an absence or a low amount of the repressive mark H3K9me2 in ex vitro conditions in plants that were cultured earlier either in M or B. Moreover, the expression of AtqKNOX1 and AtqKNOX2, on A. fourcroydes and A. angustifolia clones, is affected during in vitro conditions. Therefore, we used Chromatin ImmunoPrecipitation (ChIP) to know whether these genes were epigenetically regulated. In the case of AtqKNOX1, the H3K4me3 and H3K9me2 were affected during in vitro conditions in comparison with AtqKNOX2. Conclusions Agave clones plants with higher DNA methylation during in vitro conditions were better adapted to ex vitro conditions. In addition, A. fourcroydes and A. angustifolia clones displayed differential expression of the KNOX1 gene during in vitro conditions, which is epigenetically regulated by the H3K4me3 and H3K9me2 marks. The finding of an epigenetic regulation in key developmental genes will make it important in future studies to identify factors that help to find climate-resistant micropropagated plants. PMID:23126409

Predicting fear of heights, snakes, and public speaking from multimodal classical conditioning events.

PubMed

Wu, Ning Ying; Conger, Anthony J; Dygdon, Judith A

2006-04-01

Two hundred fifty one men and women participated in a study of the prediction of fear of heights, snakes, and public speaking by providing retrospective accounts of multimodal classical conditioning events involving those stimuli. The fears selected for study represent those believed by some to be innate (i.e., heights), prepared (i.e., snakes), and purely experientially learned (i.e., public speaking). This study evaluated the extent to which classical conditioning experiences in direct, observational, and verbal modes contributed to the prediction of the current level of fear severity. Subjects were asked to describe their current level of fear and to estimate their experience with fear response-augmenting events (first- and higher-order aversive pairings) and fear response-moderating events (first- and higher-order appetitive pairings, and pre- and post-conditioning neutral presentations) in direct, observational, and verbal modes. For each stimulus, fear was predictable from direct response-augmenting events and prediction was enhanced by the inclusion of response-moderating events. Furthermore, for each fear, maximum prediction was attained by the addition of variables tapping experiences in the observational and/or verbal modes. Conclusions are offered regarding the importance of including response-augmenting and response-moderating events in all three modes in both research and clinical applications of classical conditioning.

Odor information transfer in the stingless bee Melipona quadrifasciata: effect of in-hive experiences on classical conditioning of proboscis extension.

PubMed

Mc Cabe, Sofía I; Farina, Walter M

2009-02-01

A recent study showed that the stingless bee Melipona quadrifasciata could learn to discriminate odors in a classical conditioning of proboscis extension response (PER). Here we used this protocol to investigate the ability of these bees to use olfactory information obtained within the colony in an experimental context: the PER paradigm. We compared their success in solving a classical differential conditioning depending on the previous olfactory experiences received inside the nest. We found that M. quadrifasciata bees are capable of transferring the food-odor information acquired in the colony to a differential conditioning in the PER paradigm. Bees attained higher discrimination levels when they had previously encountered the rewarded odor associated to food inside the hive. The increase in the discrimination levels, however, was in some cases unspecific to the odor used indicating a certain degree of generalization. The influence of the food scent offered at a field feeder 24 h before the classical conditioning could also be seen in the discrimination attained by the foragers in the PER setup, detecting the presence of long-term memory. Moreover, the improved performance of recruited bees in the PER paradigm suggests the occurrence of social learning of nectar scents inside the stingless bees' hives.

The Pavlovian analysis of instrumental conditioning.

PubMed

Gormezano, I; Tait, R W

1976-01-01

An account was given of the development within the Russian literature of a uniprocess formulation of classical and instrumental conditioning, known as the bidirectional conditioning hypothesis. The hypothesis purports to offer a single set of Pavlovian principles to account for both paradigms, based upon a neural model which assumes that bidirectional (forward and backward) connections are formed in both calssical and instrumental conditioning situations. In instrumental conditioning, the bidirectional connections are hypothesized to be simply more complex than those in classical conditioning, and any differences in empirical functions are presumed to lie not in difference in mechanism, but in the strength of the forward and backward connections. Although bidirectional connections are assumed to develop in instrumental conditioning, the experimental investigation of the bidirectional conditioning hypothesis has been essentially restricted to the classical conditioning operations of pairing two CSs (sensory preconditioning training), a US followed by a CS (backward conditioning training) and two USs. However, the paradigm involving the pairing of two USs, because of theoretical and analytical considerations, is the one most commonly employed by Russian investigators. The results of an initial experiment involving the pairing of two USs, and reference to the results of a more extensive investigation, leads us to tentatively question the validity of the bidirectional conditioning account of instrumental conditioning.

A System Computational Model of Implicit Emotional Learning

PubMed Central

Puviani, Luca; Rama, Sidita

2016-01-01

Nowadays, the experimental study of emotional learning is commonly based on classical conditioning paradigms and models, which have been thoroughly investigated in the last century. Unluckily, models based on classical conditioning are unable to explain or predict important psychophysiological phenomena, such as the failure of the extinction of emotional responses in certain circumstances (for instance, those observed in evaluative conditioning, in post-traumatic stress disorders and in panic attacks). In this manuscript, starting from the experimental results available from the literature, a computational model of implicit emotional learning based both on prediction errors computation and on statistical inference is developed. The model quantitatively predicts (a) the occurrence of evaluative conditioning, (b) the dynamics and the resistance-to-extinction of the traumatic emotional responses, (c) the mathematical relation between classical conditioning and unconditioned stimulus revaluation. Moreover, we discuss how the derived computational model can lead to the development of new animal models for resistant-to-extinction emotional reactions and novel methodologies of emotions modulation. PMID:27378898

A System Computational Model of Implicit Emotional Learning.

PubMed

Puviani, Luca; Rama, Sidita

2016-01-01

Nowadays, the experimental study of emotional learning is commonly based on classical conditioning paradigms and models, which have been thoroughly investigated in the last century. Unluckily, models based on classical conditioning are unable to explain or predict important psychophysiological phenomena, such as the failure of the extinction of emotional responses in certain circumstances (for instance, those observed in evaluative conditioning, in post-traumatic stress disorders and in panic attacks). In this manuscript, starting from the experimental results available from the literature, a computational model of implicit emotional learning based both on prediction errors computation and on statistical inference is developed. The model quantitatively predicts (a) the occurrence of evaluative conditioning, (b) the dynamics and the resistance-to-extinction of the traumatic emotional responses, (c) the mathematical relation between classical conditioning and unconditioned stimulus revaluation. Moreover, we discuss how the derived computational model can lead to the development of new animal models for resistant-to-extinction emotional reactions and novel methodologies of emotions modulation.

A Temporal-Specific and Transient cAMP Increase Characterizes Odorant Classical Conditioning

ERIC Educational Resources Information Center

Cui, Wen; Smith, Andrew; Darby-King, Andrea; Harley, Carolyn W.; McLean, John H.

2007-01-01

Increases in cyclic adenosine monophosphate (cAMP) are proposed to initiate learning in a wide variety of species. Here, we measure changes in cAMP in the olfactory bulb prior to, during, and following a classically conditioned odor preference trial in rat pups. Measurements were taken up to the point of maximal CREB phosphorylation in olfactory…

2008 Gender Relations Survey of Reserve Component Members

DTIC Science & Technology

2009-03-01

Sexual coercion is defined as classic quid pro quo instances of specific treatment or favoritism conditioned on...defined by both the U.S. legal system and DoD as behaviors that might lead to a hostile work environment, or represent quid pro quo harassment ...relationship; • Sexual coercion—classic quid pro quo instances of specific treatment or favoritism conditioned on sexual cooperation. For

Monte Carlo simulations guided by imaging to predict the in vitro ranking of radiosensitizing nanoparticles

PubMed Central

Retif, Paul; Reinhard, Aurélie; Paquot, Héna; Jouan-Hureaux, Valérie; Chateau, Alicia; Sancey, Lucie; Barberi-Heyob, Muriel; Pinel, Sophie; Bastogne, Thierry

2016-01-01

This article addresses the in silico–in vitro prediction issue of organometallic nanoparticles (NPs)-based radiosensitization enhancement. The goal was to carry out computational experiments to quickly identify efficient nanostructures and then to preferentially select the most promising ones for the subsequent in vivo studies. To this aim, this interdisciplinary article introduces a new theoretical Monte Carlo computational ranking method and tests it using 3 different organometallic NPs in terms of size and composition. While the ranking predicted in a classical theoretical scenario did not fit the reference results at all, in contrast, we showed for the first time how our accelerated in silico virtual screening method, based on basic in vitro experimental data (which takes into account the NPs cell biodistribution), was able to predict a relevant ranking in accordance with in vitro clonogenic efficiency. This corroborates the pertinence of such a prior ranking method that could speed up the preclinical development of NPs in radiation therapy. PMID:27920524

Monte Carlo simulations guided by imaging to predict the in vitro ranking of radiosensitizing nanoparticles.

PubMed

Retif, Paul; Reinhard, Aurélie; Paquot, Héna; Jouan-Hureaux, Valérie; Chateau, Alicia; Sancey, Lucie; Barberi-Heyob, Muriel; Pinel, Sophie; Bastogne, Thierry

This article addresses the in silico-in vitro prediction issue of organometallic nanoparticles (NPs)-based radiosensitization enhancement. The goal was to carry out computational experiments to quickly identify efficient nanostructures and then to preferentially select the most promising ones for the subsequent in vivo studies. To this aim, this interdisciplinary article introduces a new theoretical Monte Carlo computational ranking method and tests it using 3 different organometallic NPs in terms of size and composition. While the ranking predicted in a classical theoretical scenario did not fit the reference results at all, in contrast, we showed for the first time how our accelerated in silico virtual screening method, based on basic in vitro experimental data (which takes into account the NPs cell biodistribution), was able to predict a relevant ranking in accordance with in vitro clonogenic efficiency. This corroborates the pertinence of such a prior ranking method that could speed up the preclinical development of NPs in radiation therapy.

Evaluation of the efficacy of six supraglottic devices for airway management in dark conditions: a crossover randomized simulation trial.

PubMed

Ohchi, Fumihiro; Komasawa, Nobuyasu; Imagawa, Kentaro; Okamoto, Kaori; Minami, Toshiaki

2015-12-01

During out-of-hospital cardiopulmonary resuscitation, several factors can render tracheal intubation more difficult, such as when rescuers must secure the airway in complete darkness or with limited illumination. The purpose of this study was to evaluate the efficacy of six supraglottic devices (SGDs), ProSeal(®) (ProSeal), Classic(®) (Classic), Supreme(®) (Supreme), Laryngeal Tube(®) (LT), air-Q(®) (air-Q), and i-gel(®) (i-gel), for airway management under light and dark conditions using a manikin. Seventeen novice doctors and 15 experienced doctors performed insertion of six SGDs under light and dark conditions using an adult manikin. Insertion time, successful ventilation rate, and subjective insertion difficulty on a visual analogue scale (VAS) were measured. Both novice and experienced doctors had a significantly lower ventilation success rate in the dark than in the light when ProSeal and Classic were used, but not with the other four SGDs. Novice doctors required a significantly longer insertion time in the dark than in the light with all SGDs. Experienced doctors required a significantly longer insertion time in the dark than in the light with ProSeal or Classic, but not with the other four SGDs. VAS was significantly higher for both novice and experienced doctors when ProSeal and Classic were used, as compared with the other four SGDs in the dark. Compared to ProSeal and Classic, Supreme, i-gel, LT, and air-Q are more effective for airway management in the dark. Our findings suggest that anatomically shaped SGDs may help novice doctors secure the airway under dark conditions.

Gamma-band activation predicts both associative memory and cortical plasticity

PubMed Central

Headley, Drew B.; Weinberger, Norman M.

2011-01-01

Gamma-band oscillations are a ubiquitous phenomenon in the nervous system and have been implicated in multiple aspects of cognition. In particular, the strength of gamma oscillations at the time a stimulus is encoded predicts its subsequent retrieval, suggesting that gamma may reflect enhanced mnemonic processing. Likewise, activity in the gamma-band can modulate plasticity in vitro. However, it is unclear whether experience-dependent plasticity in vivo is also related to gamma-band activation. The aim of the present study is to determine whether gamma activation in primary auditory cortex modulates both the associative memory for an auditory stimulus during classical conditioning and its accompanying specific receptive field plasticity. Rats received multiple daily sessions of single tone/shock trace and two-tone discrimination conditioning, during which local field potentials and multiunit discharges were recorded from chronically implanted electrodes. We found that the strength of tone-induced gamma predicted the acquisition of associative memory 24 h later, and ceased to predict subsequent performance once asymptote was reached. Gamma activation also predicted receptive field plasticity that specifically enhanced representation of the signal tone. This concordance provides a long-sought link between gamma oscillations, cortical plasticity and the formation of new memories. PMID:21900554

GPR30, the Non-Classical Membrane G Protein Related Estrogen Receptor, Is Overexpressed in Human Seminoma and Promotes Seminoma Cell Proliferation

PubMed Central

Chevalier, Nicolas; Vega, Aurélie; Bouskine, Adil; Siddeek, Bénazir; Michiels, Jean-François; Chevallier, Daniel; Fénichel, Patrick

2012-01-01

Background Testicular germ cell tumours are the most frequent cancer of young men with an increasing incidence all over the world. Pathogenesis and reasons of this increase remain unknown but epidemiological and clinical data have suggested that fetal exposure to environmental endocrine disruptors (EEDs) with estrogenic effects, could participate to testicular germ cell carcinogenesis. However, these EEDs (like bisphenol A) are often weak ligands for classical nuclear estrogen receptors. Several research groups recently showed that the non classical membrane G-protein coupled estrogen receptor (GPER/GPR30) mediates the effects of estrogens and several xenoestrogens through rapid non genomic activation of signal transduction pathways in various human estrogen dependent cancer cells (breast, ovary, endometrium). The aim of this study was to demonstrate that GPER was overexpressed in testicular tumours and was able to trigger JKT-1 seminoma cell proliferation. Results We report here for the first time a complete morphological and functional characterization of GPER in normal and malignant human testicular germ cells. In normal adult human testes, GPER was expressed by somatic (Sertoli cells) and germ cells (spermatogonia and spermatocytes). GPER was exclusively overexpressed in seminomas, the most frequent testicular germ cell cancer, localized at the cell membrane and triggered a proliferative effect on JKT-1 cells in vitro, which was completely abolished by G15 (a GPER selective antagonist) and by siRNA invalidation. Conclusion These results demonstrate that GPER is expressed by human normal adult testicular germ cells, specifically overexpressed in seminoma tumours and able to trigger seminoma cell proliferation in vitro. It should therefore be considered rather than classical ERs when xeno-estrogens or other endocrine disruptors are assessed in testicular germ cell cancers. It may also represent a prognosis marker and/or a therapeutic target for seminomas. PMID:22496838

Integral approximations to classical diffusion and smoothed particle hydrodynamics

DOE PAGES

Du, Qiang; Lehoucq, R. B.; Tartakovsky, A. M.

2014-12-31

The contribution of the paper is the approximation of a classical diffusion operator by an integral equation with a volume constraint. A particular focus is on classical diffusion problems associated with Neumann boundary conditions. By exploiting this approximation, we can also approximate other quantities such as the flux out of a domain. Our analysis of the model equation on the continuum level is closely related to the recent work on nonlocal diffusion and peridynamic mechanics. In particular, we elucidate the role of a volumetric constraint as an approximation to a classical Neumann boundary condition in the presence of physical boundary.more » The volume-constrained integral equation then provides the basis for accurate and robust discretization methods. As a result, an immediate application is to the understanding and improvement of the Smoothed Particle Hydrodynamics (SPH) method.« less

Neurobiology of Learning and Memory: Modulation and Mechanisms

DTIC Science & Technology

1988-08-01

Behavioral Biology, 6 (1976) pp. 45-62. Birt, D. and Olds, M., Associative response changes in lateral midbrain tegmentum and medial geniculate during...medial geniculate body of the cat during classical conditioning, Society for Neuroscience Abstracts, 6, (1976), p. 435. Ryugo, D.K. and Weinberger, N.M...Differential plasticity of morphologi- cally distinct neuron populations in the medial geniculate body of the cat during classical conditioning

Use of bovine recombinant prion protein and real-time quaking-induced conversion to detect transmissible mink encephalopathy prions and discriminate classical and atypical L- and H-type bovine spongiform encephalopathy

USDA-ARS?s Scientific Manuscript database

Prions are amyloid-forming proteins that cause transmissible spongiform encephalopathies through a process involving conversion from normal cellular prion protein to pathogenic misfolded conformation. This conversion has been used for in vitro assays including serial protein misfolding amplification...

In vitro and in vivo tissue harmonic images obtained with parallel transmit beamforming by means of orthogonal frequency division multiplexing.

PubMed

Demi, Libertario; Ramalli, Alessandro; Giannini, Gabriele; Mischi, Massimo

2015-01-01

In classic pulse-echo ultrasound imaging, the data acquisition rate is limited by the speed of sound. To overcome this, parallel beamforming techniques in transmit (PBT) and in receive (PBR) mode have been proposed. In particular, PBT techniques, based on the transmission of focused beams, are more suitable for harmonic imaging because they are capable of generating stronger harmonics. Recently, orthogonal frequency division multiplexing (OFDM) has been investigated as a means to obtain parallel beamformed tissue harmonic images. To date, only numerical studies and experiments in water have been performed, hence neglecting the effect of frequencydependent absorption. Here we present the first in vitro and in vivo tissue harmonic images obtained with PBT by means of OFDM, and we compare the results with classic B-mode tissue harmonic imaging. The resulting contrast-to-noise ratio, here used as a performance metric, is comparable. A reduction by 2 dB is observed for the case in which three parallel lines are reconstructed. In conclusion, the applicability of this technique to ultrasonography as a means to improve the data acquisition rate is confirmed.

Control of cerebellar granule cell output by sensory-evoked Golgi cell inhibition

PubMed Central

Duguid, Ian; Branco, Tiago; Chadderton, Paul; Arlt, Charlotte; Powell, Kate; Häusser, Michael

2015-01-01

Classical feed-forward inhibition involves an excitation–inhibition sequence that enhances the temporal precision of neuronal responses by narrowing the window for synaptic integration. In the input layer of the cerebellum, feed-forward inhibition is thought to preserve the temporal fidelity of granule cell spikes during mossy fiber stimulation. Although this classical feed-forward inhibitory circuit has been demonstrated in vitro, the extent to which inhibition shapes granule cell sensory responses in vivo remains unresolved. Here we combined whole-cell patch-clamp recordings in vivo and dynamic clamp recordings in vitro to directly assess the impact of Golgi cell inhibition on sensory information transmission in the granule cell layer of the cerebellum. We show that the majority of granule cells in Crus II of the cerebrocerebellum receive sensory-evoked phasic and spillover inhibition prior to mossy fiber excitation. This preceding inhibition reduces granule cell excitability and sensory-evoked spike precision, but enhances sensory response reproducibility across the granule cell population. Our findings suggest that neighboring granule cells and Golgi cells can receive segregated and functionally distinct mossy fiber inputs, enabling Golgi cells to regulate the size and reproducibility of sensory responses. PMID:26432880

Bell’s measure and implementing quantum Fourier transform with orbital angular momentum of classical light

PubMed Central

Song, Xinbing; Sun, Yifan; Li, Pengyun; Qin, Hongwei; Zhang, Xiangdong

2015-01-01

We perform Bell’s measurement for the non-separable correlation between polarization and orbital angular momentum from the same classical vortex beam. The violation of Bell’s inequality for such a non-separable classical correlation has been demonstrated experimentally. Based on the classical vortex beam and non-quantum entanglement between the polarization and the orbital angular momentum, the Hadamard gates and conditional phase gates have been designed. Furthermore, a quantum Fourier transform has been implemented experimentally. PMID:26369424

In vitro modulation of inflammatory target gene expression by a polyphenol-enriched fraction of rose oil distillation waste water.

PubMed

Wedler, Jonas; Weston, Anna; Rausenberger, Julia; Butterweck, Veronika

2016-10-01

Classical production of rose oil is based on water steam distillation from the flowers of Rosa damascena. During this process, large quantities of waste water accrue which are discharged to the environment, causing severe pollution of both, groundwater and surface water due to a high content of polyphenols. We recently developed a strategy to purify the waste water into a polyphenol-depleted and a polyphenol-enriched fraction RF20-(SP-207). RF20-(SP-207) and sub-fraction F(IV) significantly inhibited cell proliferation and migration of HaCaT cells. Since there is a close interplay between these actions and inflammatory processes, here we focused on the fractions' influence on pro-inflammatory biomarkers. HaCaT keratinocytes were treated with RF20-(SP-207), F(IV) (both at 50μg/mL) and ellagic acid (10μM) for 24h under TNF-α (20ng/mL) stimulated and non-stimulated conditions. Gene expression of IL-1β, IL-6, IL-8, RANTES and MCP-1 was analyzed by reverse transcriptase polymerase chain reaction (RT-PCR) and cellular protein secretion of IL-8, RANTES and MCP-1 was determined by ELISA based assays. RF20-(SP-207) and F(IV) significantly decreased the expression and cellular protein secretion of IL-1β, IL-6, IL-8, RANTES and MCP-1. The diminishing effects on inflammatory target gene expression were slightly less pronounced under TNF-α stimulated conditions. In conclusion, the recovered polyphenol fraction RF20-(SP-207) from rose oil distillation waste water markedly modified inflammatory target gene expression in vitro, and, therefore, could be further developed as alternative treatment of acute and chronic inflammation. Copyright © 2016 Elsevier B.V. All rights reserved.

On the Relative Relevance of Subject-Specific Geometries and Degeneration-Specific Mechanical Properties for the Study of Cell Death in Human Intervertebral Disk Models

PubMed Central

Malandrino, Andrea; Pozo, José M.; Castro-Mateos, Isaac; Frangi, Alejandro F.; van Rijsbergen, Marc M.; Ito, Keita; Wilke, Hans-Joachim; Dao, Tien Tuan; Ho Ba Tho, Marie-Christine; Noailly, Jérôme

2015-01-01

Capturing patient- or condition-specific intervertebral disk (IVD) properties in finite element models is outmost important in order to explore how biomechanical and biophysical processes may interact in spine diseases. However, disk degenerative changes are often modeled through equations similar to those employed for healthy organs, which might not be valid. As for the simulated effects of degenerative changes, they likely depend on specific disk geometries. Accordingly, we explored the ability of continuum tissue models to simulate disk degenerative changes. We further used the results in order to assess the interplay between these simulated changes and particular IVD morphologies, in relation to disk cell nutrition, a potentially important factor in disk tissue regulation. A protocol to derive patient-specific computational models from clinical images was applied to different spine specimens. In vitro, IVD creep tests were used to optimize poro-hyperelastic input material parameters in these models, in function of the IVD degeneration grade. The use of condition-specific tissue model parameters in the specimen-specific geometrical models was validated against independent kinematic measurements in vitro. Then, models were coupled to a transport-cell viability model in order to assess the respective effects of tissue degeneration and disk geometry on cell viability. While classic disk poro-mechanical models failed in representing known degenerative changes, additional simulation of tissue damage allowed model validation and gave degeneration-dependent material properties related to osmotic pressure and water loss, and to increased fibrosis. Surprisingly, nutrition-induced cell death was independent of the grade-dependent material properties, but was favored by increased diffusion distances in large IVDs. Our results suggest that in situ geometrical screening of IVD morphology might help to anticipate particular mechanisms of disk degeneration. PMID:25717471

Classic conditioning in aged rabbits: delay, trace, and long-delay conditioning.

PubMed

Solomon, P R; Groccia-Ellison, M E

1996-06-01

Young (0.5 years) and aged (2+, 3+, and 4+ years) rabbits underwent acquisition of the classically conditioned nictitating membrane response in a delay (500-ms conditioned stimulus [CS], 400-ms interstimulus interval [ISI]), long-delay (1,000-ms CS, 900-ms ISI), or trace (500-ms CS, 400-ms stimulus-free period) paradigm. Collapsing across age groups, there is a general tendency for animals to acquire trace conditioning more slowly than delay conditioning. Collapsing across conditioning paradigms, there is a general tendency for aged animals to acquire more slowly than younger animals. Of greater significance, however, are the age differences in the different conditioning paradigms. In the delay and long-delay paradigms, significant conditioning deficits first appeared in the 4(+)-year-old group. In the trace conditioning paradigm, significant conditioning deficits became apparent in the 2(+)-year-old animals.

Selection of Classical Swine Fever Virus with Enhanced Pathogenicity Reveals Synergistic Virulence Determinants in E2 and NS4B

PubMed Central

Tamura, Tomokazu; Yoshino, Fumi; Nomura, Takushi; Yamamoto, Naoki; Sato, Yuka; Okamatsu, Masatoshi; Ruggli, Nicolas; Kida, Hiroshi

2012-01-01

Classical swine fever virus (CSFV) is the causative agent of classical swine fever (CSF), a highly contagious disease of pigs. There are numerous CSFV strains that differ in virulence, resulting in clinical disease with different degrees of severity. Low-virulent and moderately virulent isolates cause a mild and often chronic disease, while highly virulent isolates cause an acute and mostly lethal hemorrhagic fever. The live attenuated vaccine strain GPE− was produced by multiple passages of the virulent ALD strain in cells of swine, bovine, and guinea pig origin. With the aim of identifying the determinants responsible for the attenuation, the GPE− vaccine virus was readapted to pigs by serial passages of infected tonsil homogenates until prolonged viremia and typical signs of CSF were observed. The GPE−/P-11 virus isolated from the tonsils after the 11th passage in vivo had acquired 3 amino acid substitutions in E2 (T830A) and NS4B (V2475A and A2563V) compared with the virus before passages. Experimental infection of pigs with the mutants reconstructed by reverse genetics confirmed that these amino acid substitutions were responsible for the acquisition of pathogenicity. Studies in vitro indicated that the substitution in E2 influenced virus spreading and that the changes in NS4B enhanced the viral RNA replication. In conclusion, the present study identified residues in E2 and NS4B of CSFV that can act synergistically to influence virus replication efficiency in vitro and pathogenicity in pigs. PMID:22674973

On the constrained classical capacity of infinite-dimensional covariant quantum channels

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

Holevo, A. S.

The additivity of the minimal output entropy and that of the χ-capacity are known to be equivalent for finite-dimensional irreducibly covariant quantum channels. In this paper, we formulate a list of conditions allowing to establish similar equivalence for infinite-dimensional covariant channels with constrained input. This is then applied to bosonic Gaussian channels with quadratic input constraint to extend the classical capacity results of the recent paper [Giovannetti et al., Commun. Math. Phys. 334(3), 1553-1571 (2015)] to the case where the complex structures associated with the channel and with the constraint operator need not commute. In particular, this implies a multimodemore » generalization of the “threshold condition,” obtained for single mode in Schäfer et al. [Phys. Rev. Lett. 111, 030503 (2013)], and the proof of the fact that under this condition the classical “Gaussian capacity” resulting from optimization over only Gaussian inputs is equal to the full classical capacity. Complex structures correspond to different squeezings, each with its own normal modes, vacuum and coherent states, and the gauge. Thus our results apply, e.g., to multimode channels with a squeezed Gaussian noise under the standard input energy constraint, provided the squeezing is not too large as to violate the generalized threshold condition. We also investigate the restrictiveness of the gauge-covariance condition for single- and multimode bosonic Gaussian channels.« less

Classical versus quantum dynamical chaos: Sensitivity to external perturbations, stability and reversibility

NASA Astrophysics Data System (ADS)

Sokolov, Valentin V.; Zhirov, Oleg V.; Kharkov, Yaroslav A.

The extraordinary complexity of classical trajectories of typical nonlinear systems that manifest stochastic behavior is intimately connected with exponential sensitivity to small variations of initial conditions and/or weak external perturbations. In rigorous terms, such classical systems are characterized by positive algorithmic complexity described by the Lyapunov exponent or, alternatively, by the Kolmogorov-Sinai entropy. The said implies that, in spite of the fact that, formally, any however complex trajectory of a perfectly isolated (closed) system is unique and differentiable for any certain initial conditions and the motion is perfectly reversible, it is impractical to treat that sort of classical systems as closed ones. Inevitably, arbitrary weak influence of an environment crucially impacts the dynamics. This influence, that can be considered as a noise, rapidly effaces the memory of initial conditions and turns the motion into an irreversible random process. In striking contrast, the quantum mechanics of the classically chaotic systems exhibit much weaker sensitivity and strong memory of the initial state. Qualitatively, this crucial difference could be expected in view of a much simpler structure of quantum states as compared to the extraordinary complexity of random and unpredictable classical trajectories. However the very notion of trajectories is absent in quantum mechanics so that the concept of exponential instability seems to be irrelevant in this case. The problem of a quantitative measure of complexity of a quantum state of motion, that is a very important and nontrivial issue of the theory of quantum dynamical chaos, is the one of our concern. With such a measure in hand, we quantitatively analyze the stability and reversibility of quantum dynamics in the presence of external noise. To solve this problem we point out that individual classical trajectories are of minor interest if the motion is chaotic. Properties of all of them are alike in this case and rather the behavior of their manifolds carries really valuable information. Therefore the phase-space methods and, correspondingly, the Liouville form of the classical mechanics become the most adequate. It is very important that, opposite to the classical trajectories, the classical phase space distribution and the Liouville equation have direct quantum analogs. Hence, the analogy and difference of classical and quantum dynamics can be traced by comparing the classical (W(c)(I,θ;t)) and quantum (Wigner function W(I,θ;t)) phase space distributions both expressed in identical phase-space variables but ruled by different(!) linear equations. The paramount property of the classical dynamical chaos is the exponentially fast structuring of the system's phase space on finer and finer scales. On the contrary, degree of structuring of the corresponding Wigner function is restricted by the quantization of the phase space. This makes Wigner function more coarse and relatively "simple" as compared to its classical counterpart. Fourier analysis affords quite suitable ground for analyzing complexity of a phase space distribution, that is equally valid in classical and quantum cases. We demonstrate that the typical number of Fourier harmonics is indeed a relevant measure of complexity of states of motion in both classical as well as quantum cases. This allowed us to investigate in detail and introduce a quantitative measure of sensitivity to an external noisy environment and formulate the conditions under which the quantum motion remains reversible. It turns out that while the mean number of harmonics of the classical phase-space distribution of a non-integrable system grows with time exponentially during the whole time of the motion, the time of exponential upgrowth of this number in the case of the corresponding quantum Wigner function is restricted only to the Ehrenfest interval 0 < t < tE - just the interval within which the Wigner function still satisfies the classical Liouville equation. We showed that the number of harmonics increases beyond this interval algebraically. This fact gains a crucial importance when the Ehrenfest time is so short that the exponential regime has no time to show up. Under this condition the quantum motion turns out to be quite stable and reversible.

FabQ, a Dual-Function Dehydratase/Isomerase, Circumvents the Last Step of the Classical Fatty Acid Synthesis Cycle

PubMed Central

Bi, Hongkai; Wang, Haihong; Cronan, John E.

2015-01-01

SUMMARY In the classical anaerobic pathway of unsaturated fatty acid biosynthesis, that of Escherichia coli, the double bond is introduced into the growing acyl chain by the FabA dehydratase/isomerase. Another dehydratase, FabZ, functions in the chain elongation cycle. In contrast, Aerococcus viridans has only a single FabA/FabZ homolog we designate FabQ. FabQ can not only replace the function of E. coli FabZ in vivo, but it also catalyzes the isomerization required for unsaturated fatty acid biosynthesis. Most strikingly, FabQ in combination with E. coli FabB imparts the surprising ability to bypass reduction of the trans-2-acyl-ACP intermediates of classical fatty acid synthesis. FabQ allows elongation by progressive isomerization reactions to form the polyunsaturated fatty acid, 3-hydroxy-cis-5, 7-hexadecadienoic acid, both in vitro and in vivo. FabQ therefore provides a potential pathway for bacterial synthesis of polyunsaturated fatty acids. PMID:23972938

A functional and thromboelastometric-based micromethod for assessing crotoxin anticoagulant activity and antiserum relative potency against Crotalus durissus terrificus venom.

PubMed

Prezoto, B C; Tanaka-Azevedo, A M; Marcelino, J R; Tashima, A K; Nishiduka, E S; Kapronezai, J; Mota, J O; Rocha, M M T; Serino-Silva, C; Oguiura, N

2018-06-15

The assessment of the capacity of antivenoms to neutralize the lethal activity of snake venoms still relies on traditional rodent in vivo lethality assay. ED 50 and LD 50 assays require large quantities of venoms and antivenoms, and besides leading to animal suffering. Therefore, in vitro tests should be introduced for assessing antivenom neutralizing capacity in intermediary steps of antivenom production. This task is facilitated when one key lethal toxin is identified. A good example is crotoxin, a β-neurotoxin phospholipase A 2 -like toxin that presents anticoagulant activity in vitro and is responsible for the lethality of venoms of Crotalus durissus snakes. By using rotational thromboelastometry, we reported recently one sensitive coagulation assay for assessing relative potency of the anti-bothropic serum in neutralizing procoagulant activity of Bothrops jararaca venom upon recalcified factor-XII-deficient chicken plasma samples (CPS). In this study, we stablished conditions for determining relative potency of four batches of the anti-crotalic serum (ACS) (antagonist) in inactivating crotoxin anticoagulant activity in CPS (target) simultaneously treated with one classical activator of coagulation (agonists). The correlation coefficient (r) between values related the ACS potency in inactivating both in vitro crotoxin anticoagulant activity and the in vivo lethality of whole venom (ED 50 ) was 0.94 (p value < 0.05). In conclusion, slowness in spontaneous thrombin/fibrin generation even after recalcification elicit time lapse sufficient for elaboration of one dose-response curve to pro- or anti-coagulant agonists in CPS. We propose this methodology as an alternative and sensitive assay for assessing antivenom neutralizing ability in plasma of immunized horses as well as for in-process quality control. Copyright © 2018 Elsevier Ltd. All rights reserved.

Ultimate open pit stochastic optimization

NASA Astrophysics Data System (ADS)

Marcotte, Denis; Caron, Josiane

2013-02-01

Classical open pit optimization (maximum closure problem) is made on block estimates, without directly considering the block grades uncertainty. We propose an alternative approach of stochastic optimization. The stochastic optimization is taken as the optimal pit computed on the block expected profits, rather than expected grades, computed from a series of conditional simulations. The stochastic optimization generates, by construction, larger ore and waste tonnages than the classical optimization. Contrary to the classical approach, the stochastic optimization is conditionally unbiased for the realized profit given the predicted profit. A series of simulated deposits with different variograms are used to compare the stochastic approach, the classical approach and the simulated approach that maximizes expected profit among simulated designs. Profits obtained with the stochastic optimization are generally larger than the classical or simulated pit. The main factor controlling the relative gain of stochastic optimization compared to classical approach and simulated pit is shown to be the information level as measured by the boreholes spacing/range ratio. The relative gains of the stochastic approach over the classical approach increase with the treatment costs but decrease with mining costs. The relative gains of the stochastic approach over the simulated pit approach increase both with the treatment and mining costs. At early stages of an open pit project, when uncertainty is large, the stochastic optimization approach appears preferable to the classical approach or the simulated pit approach for fair comparison of the values of alternative projects and for the initial design and planning of the open pit.

New potential solutions for the chemolysis of urinary phosphate calculi determined by an in vitro study.

PubMed

Zhang, Jinqing; Wang, Shuo; Hong, Jingfan; Liu, Chunxiao; Jiang, Yanbin

2015-04-01

To find a more efficient solution for chemolysis of urinary calculi, several organic acids were chosen to form solutions by consulting the composition of a classic solution, Suby G. The solutions together with Renacidin, another classic solution, were designed to react with the 4 phosphate components of urinary stone. The processes were real-time measured and analysed by a focused beam reflectance measurement, and the efficiency factors were investigated and discussed in detail. The results show that several organic acids, e.g. hydroxyacetic acid, lactic acid and α-ketoglutaric acid, are more efficient than citric acid in dissolving urinary phosphate calculus. The new solutions containing the organic acids are promising for improving chemolysis treatment.

Cytotoxicity assessment of antibiofouling compounds and by-products in marine bivalve cell cultures.

PubMed

Domart-Coulon, I; Auzoux-Bordenave, S; Doumenc, D; Khalanski, M

2000-06-01

Short-term primary cell cultures were derived from adult marine bivalve tissues: the heart of oyster Crassostrea gigas and the gill of clam Ruditapes decussatus. These cultures were used as experimental in vitro models to assess the acute cytotoxicity of an organic molluscicide, Mexel-432, used in antibiofouling treatments in industrial cooling water systems. A microplate cell viability assay, based on the enzymatic reduction of tetrazolium dye (MTT) in living bivalve cells, was adapted to test the cytotoxicity of this compound: in both in vitro models, toxicity thresholds of Mexel-432 were compared to those determined in vivo with classic acute toxicity tests. The clam gill cell model was also used to assess the cytotoxicity of by-products of chlorination, a major strategy of biofouling control in the marine environment. The applications and limits of these new in vitro models for monitoring aquatic pollutants were discussed, in reference with the standardized Microtox test.

In vitro synchrotron-based radiography of micro-gap formation at the implant-abutment interface of two-piece dental implants.

PubMed

Rack, A; Rack, T; Stiller, M; Riesemeier, H; Zabler, S; Nelson, K

2010-03-01

Micro-gap formation at the implant-abutment interface of two-piece dental implants was investigated in vitro using high-resolution radiography in combination with hard X-ray synchrotron radiation. Images were taken with the specimen under different mechanical loads of up to 100 N. The aim of this investigation was to prove the existence of micro-gaps for implants with conical connections as well as to study the mechanical behavior of the mating zone of conical implants during loading. Synchrotron-based radiography in comparison with classical laboratory radiography yields high spatial resolution in combination with high contrast even when exploiting micro-sized features in highly attenuating objects. The first illustration of a micro-gap which was previously indistinguishable by laboratory methods underlines that the complex micro-mechanical behavior of implants requires further in vitro investigations where synchrotron-based micro-imaging is one of the prerequisites.

Analysis of the shapes of hemocytes of Callista brevisiphonata in vitro (Bivalvia, Veneridae).

PubMed

Karetin, Yu A; Pushchin, I I

2015-08-01

Fractal formalism in conjunction with linear methods of image analysis is suitable for the comparative analysis of such "irregular" shapes (from the point of view of classical Euclidean geometry) as flattened amoeboid cells of invertebrates in vitro. Cell morphology of in vitro spreading hemocytes from the bivalve mollusc Callista brevisiphonata was analyzed using correlation, factor and cluster analysis. Four significantly different cell types were identified on the basis of 36 linear and nonlinear parameters. The analysis confirmed the adequacy of the selected methodology for numerical description of the shape and the adequacy of classification of nonlinear shapes of spread hemocytes belonging to the same species. Investigation has practical significance for the description of the morphology of cultured cells, since cell shape is a result of summation of a number of extracellular and intracellular factors. © 2015 International Society for Advancement of Cytometry.

Effects of Paradigm and Inter-Stimulus Interval on Age Differences in Eyeblink Classical Conditioning in Rabbits

ERIC Educational Resources Information Center

Woodruff-Pak, Diana S.; Seta, Susan E.; Roker, LaToya A.; Lehr, Melissa A.

2007-01-01

The aim of this study was to examine parameters affecting age differences in eyeblink classical conditioning in a large sample of young and middle-aged rabbits. A total of 122 rabbits of mean ages of 4 or 26 mo were tested at inter-stimulus intervals (ISIs) of 600 or 750 msec in the delay or trace paradigms. Paradigm affected both age groups…

Microsecond Unfolding Kinetics of Sheep Prion Protein Reveals an Intermediate that Correlates with Susceptibility to Classical Scrapie

PubMed Central

Chen, Kai-Chun; Xu, Ming; Wedemeyer, William J.; Roder, Heinrich

2011-01-01

The microsecond folding and unfolding kinetics of ovine prion proteins (ovPrP) were measured under various solution conditions. A fragment comprising residues 94–233 of the full-length ovPrP was studied for four variants with differing susceptibilities to classical scrapie in sheep. The observed biexponential unfolding kinetics of ovPrP provides evidence for an intermediate species. However, in contrast to previous results for human PrP, there is no evidence for an intermediate under refolding conditions. Global analysis of the kinetic data, based on a sequential three-state mechanism, quantitatively accounts for all folding and unfolding data as a function of denaturant concentration. The simulations predict that an intermediate accumulates under both folding and unfolding conditions, but is observable only in unfolding experiments because the intermediate is optically indistinguishable from the native state. The relative population of intermediates in two ovPrP variants, both transiently and under destabilizing equilibrium conditions, correlates with their propensities for classical scrapie. The variant susceptible to classical scrapie has a larger population of the intermediate state than the resistant variant. Thus, the susceptible variant should be favored to undergo the PrPC to PrPSc conversion and oligomerization. PMID:21889460

Simulated food effects on drug release from ethylcellulose: PVA-PEG graft copolymer-coated pellets.

PubMed

Muschert, Susanne; Siepmann, Florence; Leclercq, Bruno; Carlin, Brian; Siepmann, Juergen

2010-02-01

Food effects might substantially alter drug release from oral controlled release dosage forms in vivo. The robustness of a novel type of controlled release film coating was investigated using various types of release media and two types of release apparatii. Importantly, none of the investigated conditions had a noteworthy impact on the release of freely water-soluble diltiazem HCl or slightly water-soluble theophylline from pellets coated with ethylcellulose containing small amounts of PVA-PEG graft copolymer. In particular, the presence of significant amounts of fats, carbohydrates, surfactants, bile salts, and calcium ions in the release medium did not alter drug release. Furthermore, changes in the pH and differences in the mechanical stress the dosage forms were exposed to did not affect drug release from the pellets. The investigated film coatings allowing for oral controlled drug delivery are highly robust in vitro and likely to be poorly sensitive to classical food effects in vivo.

Cell-Free Protein Synthesis: Pros and Cons of Prokaryotic and Eukaryotic Systems

PubMed Central

Zemella, Anne; Thoring, Lena; Hoffmeister, Christian; Kubick, Stefan

2015-01-01

From its start as a small-scale in vitro system to study fundamental translation processes, cell-free protein synthesis quickly rose to become a potent platform for the high-yield production of proteins. In contrast to classical in vivo protein expression, cell-free systems do not need time-consuming cloning steps, and the open nature provides easy manipulation of reaction conditions as well as high-throughput potential. Especially for the synthesis of difficult to express proteins, such as toxic and transmembrane proteins, cell-free systems are of enormous interest. The modification of the genetic code to incorporate non-canonical amino acids into the target protein in particular provides enormous potential in biotechnology and pharmaceutical research and is in the focus of many cell-free projects. Many sophisticated cell-free systems for manifold applications have been established. This review describes the recent advances in cell-free protein synthesis and details the expanding applications in this field. PMID:26478227

A Cognitive Model Based on Neuromodulated Plasticity

PubMed Central

Ruan, Xiaogang

2016-01-01

Associative learning, including classical conditioning and operant conditioning, is regarded as the most fundamental type of learning for animals and human beings. Many models have been proposed surrounding classical conditioning or operant conditioning. However, a unified and integrated model to explain the two types of conditioning is much less studied. Here, a model based on neuromodulated synaptic plasticity is presented. The model is bioinspired including multistored memory module and simulated VTA dopaminergic neurons to produce reward signal. The synaptic weights are modified according to the reward signal, which simulates the change of associative strengths in associative learning. The experiment results in real robots prove the suitability and validity of the proposed model. PMID:27872638

Modelling individual differences in the form of Pavlovian conditioned approach responses: a dual learning systems approach with factored representations.

PubMed

Lesaint, Florian; Sigaud, Olivier; Flagel, Shelly B; Robinson, Terry E; Khamassi, Mehdi

2014-02-01

Reinforcement Learning has greatly influenced models of conditioning, providing powerful explanations of acquired behaviour and underlying physiological observations. However, in recent autoshaping experiments in rats, variation in the form of Pavlovian conditioned responses (CRs) and associated dopamine activity, have questioned the classical hypothesis that phasic dopamine activity corresponds to a reward prediction error-like signal arising from a classical Model-Free system, necessary for Pavlovian conditioning. Over the course of Pavlovian conditioning using food as the unconditioned stimulus (US), some rats (sign-trackers) come to approach and engage the conditioned stimulus (CS) itself - a lever - more and more avidly, whereas other rats (goal-trackers) learn to approach the location of food delivery upon CS presentation. Importantly, although both sign-trackers and goal-trackers learn the CS-US association equally well, only in sign-trackers does phasic dopamine activity show classical reward prediction error-like bursts. Furthermore, neither the acquisition nor the expression of a goal-tracking CR is dopamine-dependent. Here we present a computational model that can account for such individual variations. We show that a combination of a Model-Based system and a revised Model-Free system can account for the development of distinct CRs in rats. Moreover, we show that revising a classical Model-Free system to individually process stimuli by using factored representations can explain why classical dopaminergic patterns may be observed for some rats and not for others depending on the CR they develop. In addition, the model can account for other behavioural and pharmacological results obtained using the same, or similar, autoshaping procedures. Finally, the model makes it possible to draw a set of experimental predictions that may be verified in a modified experimental protocol. We suggest that further investigation of factored representations in computational neuroscience studies may be useful.

Modelling Individual Differences in the Form of Pavlovian Conditioned Approach Responses: A Dual Learning Systems Approach with Factored Representations

PubMed Central

Lesaint, Florian; Sigaud, Olivier; Flagel, Shelly B.; Robinson, Terry E.; Khamassi, Mehdi

2014-01-01

Reinforcement Learning has greatly influenced models of conditioning, providing powerful explanations of acquired behaviour and underlying physiological observations. However, in recent autoshaping experiments in rats, variation in the form of Pavlovian conditioned responses (CRs) and associated dopamine activity, have questioned the classical hypothesis that phasic dopamine activity corresponds to a reward prediction error-like signal arising from a classical Model-Free system, necessary for Pavlovian conditioning. Over the course of Pavlovian conditioning using food as the unconditioned stimulus (US), some rats (sign-trackers) come to approach and engage the conditioned stimulus (CS) itself – a lever – more and more avidly, whereas other rats (goal-trackers) learn to approach the location of food delivery upon CS presentation. Importantly, although both sign-trackers and goal-trackers learn the CS-US association equally well, only in sign-trackers does phasic dopamine activity show classical reward prediction error-like bursts. Furthermore, neither the acquisition nor the expression of a goal-tracking CR is dopamine-dependent. Here we present a computational model that can account for such individual variations. We show that a combination of a Model-Based system and a revised Model-Free system can account for the development of distinct CRs in rats. Moreover, we show that revising a classical Model-Free system to individually process stimuli by using factored representations can explain why classical dopaminergic patterns may be observed for some rats and not for others depending on the CR they develop. In addition, the model can account for other behavioural and pharmacological results obtained using the same, or similar, autoshaping procedures. Finally, the model makes it possible to draw a set of experimental predictions that may be verified in a modified experimental protocol. We suggest that further investigation of factored representations in computational neuroscience studies may be useful. PMID:24550719

Emerging role of mesenchymal stem cells during tuberculosis: The fifth element in cell mediated immunity.

PubMed

Khan, Arshad; Hunter, Robert L; Jagannath, Chinnaswamy

2016-12-01

Mesenchymal stem cells (MSCs) are non-hematopoietic cells that occur in almost all human tissues and can be cultured and expanded to large numbers in vitro. They secrete growth factors, cytokines, and chemokines and express Toll-like receptors on their surface, although multiple cell biological mechanisms remain unclear. MSCs are multi-potent and can differentiate into many cell types including adipocytes, neuronal cells and osteoclasts. Despite gaps in cell biology, because of their immunomodulatory and regenerative capacity, several hundred clinical trials have used MSCs for therapy of cancer, autoimmune diseases and control of inflammation during organ transplantation. MSCs secrete immune-modulatory factors and are able to skew T cell responses and shift M1 to M2 differentiation of macrophages. We review the emerging role of MSCs to act as phagocytes for Mycobacterium tuberculosis and its role during the persistence of M. tuberculosis and spread of infection. Paradoxically, MSCs use innate defense mechanisms of autophagy and nitric oxide to inhibit the growth of intracellular M. tuberculosis. In addition, transplantation with autologous MSCs improved the clinical condition of patients with multi-drug resistant tuberculosis. Thus, in addition to the well-known immune defense played by macrophages, DCs, classical T cells and non-classical immune cells, MSCs have emerged as a fifth element capable of regulating immune responses during tuberculosis. We discuss their immunomodulatory properties and innate defense mechanisms in the context of developing immunotherapeutic strategies for tuberculosis. Published by Elsevier Ltd.

Spectral derivation of the classic laws of wall-bounded turbulent flows.

PubMed

Gioia, Gustavo; Chakraborty, Pinaki

2017-08-01

We show that the classic laws of the mean-velocity profiles (MVPs) of wall-bounded turbulent flows-the 'law of the wall,' the 'defect law' and the 'log law'-can be predicated on a sufficient condition with no manifest ties to the MVPs, namely that viscosity and finite turbulent domains have a depressive effect on the spectrum of turbulent energy. We also show that this sufficient condition is consistent with empirical data on the spectrum and may be deemed a general property of the energetics of wall turbulence. Our findings shed new light on the physical origin of the classic laws and their immediate offshoot, Prandtl's theory of turbulent friction.

Transport studies in high-performance field reversed configuration plasmas

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

Gupta, S., E-mail: sgupta@trialphaenergy.com; Barnes, D. C.; Dettrick, S. A.

2016-05-15

A significant improvement of field reversed configuration (FRC) lifetime and plasma confinement times in the C-2 plasma, called High Performance FRC regime, has been observed with neutral beam injection (NBI), improved edge stability, and better wall conditioning [Binderbauer et al., Phys. Plasmas 22, 056110 (2015)]. A Quasi-1D (Q1D) fluid transport code has been developed and employed to carry out transport analysis of such C-2 plasma conditions. The Q1D code is coupled to a Monte-Carlo code to incorporate the effect of fast ions, due to NBI, on the background FRC plasma. Numerically, the Q1D transport behavior with enhanced transport coefficients (butmore » with otherwise classical parametric dependencies) such as 5 times classical resistive diffusion, classical thermal ion conductivity, 20 times classical electron thermal conductivity, and classical fast ion behavior fit with the experimentally measured time evolution of the excluded flux radius, line-integrated density, and electron/ion temperature. The numerical study shows near sustainment of poloidal flux for nearly 1 ms in the presence of NBI.« less

Organ culture as a technique for casual embryology and its application in radiobiology (in German)

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

BORGHESE, ELIO

1961-11-01

The classical methods of experimental embryology in amplubia are compared with the more recently introduced technique of culture in vitro of embryonic organs of warmblooded animals. Some isolation and recombination experiments carried out by means of organ culture are described. It is shown, by examples taken from research in progress, how this technique is applicable radiobiological experiments.

Associative Processes in Early Olfactory Preference Acquisition

PubMed Central

Sullivan, Regina M.; Wilson, Donald A.; Leon, Michael

2007-01-01

Acquisition of behavioral conditioned responding and learned odor preferences during olfactory classical conditioning in rat pups requires forward or simultaneous pairings of the conditioned stimulus (CS) and the unconditioned stimulus (US). Other temporal relationships between the CS and US do not usually result in learning. The present study examined the influence of this CS-US relationship upon the neural olfactory bulb modifications that are acquired during early classical conditioning. Wistar rat pups were trained from Postnatal Days (PN) 1-18 with either forward (odor overlapping temporally with reinforcing stroking) or backward (stroking followed by odor) CS-US pairings. On PN 19, pups received either a behavioral odor preference test to the odor CS or an injection of 14C 2-DG and exposure to the odor CS, or olfactory bulb single unit responses were recorded in response to exposure to the odor CS. Only pups that received forward presentations of the CS and US exhibited both a preference for the CS and modified olfactory bulb neural responses to the CS. These results, then, suggest that the modified olfactory bulb neural responses acquired during classical conditioning are guided by the same temporal constraints as those which govern the acquisition of behavioral conditioned responses. PMID:17572798

In vitro dynamic model simulating the digestive tract of 6-month-old infants

PubMed Central

Gallo, Marianna; Tornatore, Fabio; Frasso, Annalisa; Saccone, Giulia; Budelli, Andrea; Barone, Maria V.

2017-01-01

Background In vivo assays cannot always be conducted because of ethical reasons, technical constraints or costs, but a better understanding of the digestive process, especially in infants, could be of great help in preventing food-related pathologies and in developing new formulas with health benefits. In this context, in vitro dynamic systems to simulate human digestion and, in particular, infant digestion could become increasingly valuable. Objective To simulate the digestive process through the use of a dynamic model of the infant gastroenteric apparatus to study the digestibility of starch-based infant foods. Design Using M.I.D.A (Model of an Infant Digestive Apparatus), the oral, gastric and intestinal digestibility of two starch-based products were measured: 1) rice starch mixed with distilled water and treated using two different sterilization methods (the classical method with a holding temperature of 121°C for 37 min and the HTST method with a holding temperature of 137°C for 70 sec) and 2) a rice cream with (premium product) or without (basic product) an aliquot of rice flour fermented by Lactobacillus paracasei CBA L74. After the digestion the foods were analyzed for the starch concentration, the amount of D-glucose released and the percentage of hydrolyzed starch. Results An in vitro dynamic system, which was referred to as M.I.D.A., was obtained. Using this system, the starch digestion occurred only during the oral and intestinal phase, as expected. The D-glucose released during the intestinal phase was different between the classical and HTST methods (0.795 grams for the HTST versus 0.512 for the classical product). The same analysis was performed for the basic and premium products. In this case, the premium product had a significant difference in terms of the starch hydrolysis percentage during the entire process. Conclusions The M.I.D.A. system was able to digest simple starches and a more complex food in the correct compartments. In this study, better digestibility of the premium product was revealed. PMID:29261742

Sfp1 and Rtg3 reciprocally modulate carbon source‐conditional stress adaptation in the pathogenic yeast Candida albicans

PubMed Central

Kastora, Stavroula L.; Herrero‐de‐Dios, Carmen; Avelar, Gabriela M.; Munro, Carol A.

2017-01-01

Summary The pathogenicity of the clinically important yeast, Candida albicans, is dependent on robust responses to host‐imposed stresses. These stress responses have generally been dissected in vitro at 30°C on artificial growth media that do not mimic host niches. Yet host inputs, such as changes in carbon source or temperature, are known to affect C. albicans stress adaptation. Therefore, we performed screens to identify novel regulators that promote stress resistance during growth on a physiologically relevant carboxylic acid and at elevated temperatures. These screens revealed that, under these ‘non‐standard’ growth conditions, numerous uncharacterised regulators are required for stress resistance in addition to the classical Hog1, Cap1 and Cta4 stress pathways. In particular, two transcription factors (Sfp1 and Rtg3) promote stress resistance in a reciprocal, carbon source‐conditional manner. SFP1 is induced in stressed glucose‐grown cells, whereas RTG3 is upregulated in stressed lactate‐grown cells. Rtg3 and Sfp1 regulate the expression of key stress genes such as CTA4, CAP1 and HOG1 in a carbon source‐dependent manner. These mechanisms underlie the stress sensitivity of C. albicans sfp1 cells during growth on glucose, and rtg3 cells on lactate. The data suggest that C. albicans exploits environmentally contingent regulatory mechanisms to retain stress resistance during host colonisation. PMID:28574606

On the importance of an accurate representation of the initial state of the system in classical dynamics simulations

NASA Astrophysics Data System (ADS)

García-Vela, A.

2000-05-01

A definition of a quantum-type phase-space distribution is proposed in order to represent the initial state of the system in a classical dynamics simulation. The central idea is to define an initial quantum phase-space state of the system as the direct product of the coordinate and momentum representations of the quantum initial state. The phase-space distribution is then obtained as the square modulus of this phase-space state. The resulting phase-space distribution closely resembles the quantum nature of the system initial state. The initial conditions are sampled with the distribution, using a grid technique in phase space. With this type of sampling the distribution of initial conditions reproduces more faithfully the shape of the original phase-space distribution. The method is applied to generate initial conditions describing the three-dimensional state of the Ar-HCl cluster prepared by ultraviolet excitation. The photodissociation dynamics is simulated by classical trajectories, and the results are compared with those of a wave packet calculation. The classical and quantum descriptions are found in good agreement for those dynamical events less subject to quantum effects. The classical result fails to reproduce the quantum mechanical one for the more strongly quantum features of the dynamics. The properties and applicability of the phase-space distribution and the sampling technique proposed are discussed.

In Situ and In Vitro Effects of Two Bleaching Treatments on Human Enamel Hardness.

PubMed

Henn-Donassollo, Sandrina; Fabris, Cristiane; Gagiolla, Morgana; Kerber, Ícaro; Caetano, Vinícius; Carboni, Vitor; Salas, Mabel Miluska Suca; Donassollo, Tiago Aurélio; Demarco, Flávio Fernando

2016-01-01

The aim of this study was to evaluate in vitro and in situ the effects of two bleaching treatments on human enamel surface microhardness. Sixty enamel slabs from recently extracted thirty molars were used. The specimens were polished with sandpapers under water-cooling. The enamel samples were randomly divided in four groups, treated with 10% hydrogen peroxide (HP) or Whitening Strips (WS) containing 10% hydrogen peroxide and using two conditions: in vitro or in situ model. For in situ condition, six volunteers wore an intra-oral appliance containing enamel slabs, while for in vitro condition the specimens were kept in deionized water after the bleaching protocols. The bleaching treatments were applied one-hour daily for 14 days. Similar amounts of bleaching agents were used in both conditions. Before and after bleaching treatments, microhardness was measured. Statistical analysis (ANOVA and Tukey test) showed that in the in situ condition there was no statistically significant microhardness reduction in the bleached enamel (p>0.05). Significant decrease in hardness was observed for enamel slabs bleached with both treatments in the in vitro condition (p<0.05). Regarding the bleaching agents, in situ results showed no difference between HP and WS, while in vitro WS produced the lowest hardness value. It could be concluded that there was no deleterious effect on enamel produced by any of the bleaching protocols used in the in situ model. The reduction of hardness was only observed in vitro.

Psoriasis: classical and emerging comorbidities*

PubMed Central

de Oliveira, Maria de Fátima Santos Paim; Rocha, Bruno de Oliveira; Duarte, Gleison Vieira

2015-01-01

Psoriasis is a chronic inflammatory systemic disease. Evidence shows an association of psoriasis with arthritis, depression, inflammatory bowel disease and cardiovascular diseases. Recently, several other comorbid conditions have been proposed as related to the chronic inflammatory status of psoriasis. The understanding of these conditions and their treatments will certainly lead to better management of the disease. The present article aims to synthesize the knowledge in the literature about the classical and emerging comorbidities related to psoriasis. PMID:25672294

Department of Defense Annual Report on Sexual Assault in the Military. Fiscal Year 2012. Volume 2

DTIC Science & Technology

2013-01-01

sexual relationship – Sexual Coercion – four items regarding classic quid pro quo instances of special treatment or favoritism conditioned on sexual ...relationship – Sexual Coercion – four items regarding classic quid pro quo instances of special treatment or favoritism conditioned on sexual ...and sexual harassment response and prevention in the military. This survey note discusses findings from the 2012 Workplace and Gender Relations

2012 Workplace and Gender Relations Survey of Reserve Component Members. Tabulation of Responses

DTIC Science & Technology

2013-05-08

Sexual Coercion can be defined as classic quid pro quo , instances of special treatment or... quid pro quo instances of job benefits or losses conditioned on sexual cooperation. Respondents were asked to indicate how often they had been in...Constructed from Q56k-l and o-p. Sexual Coercion can be defined as classic quid pro quo , instances of special treatment or favoritism conditional on sexual

2006 Workplace and Gender Relations Survey of Active Duty Members: Tabulations of Responses. Volume 2: Coast Guard Members

DTIC Science & Technology

2008-07-01

Sexual Coercion can be defined as classic quid pro quo , instances of special treatment or favoritism conditional on sexual cooperation...from Q35k-l and Q35o-p. Sexual Coercion can be defined as classic quid pro quo , instances of special treatment or favoritism conditional on sexual ...53 15. To what extent do/would you feel safe during deployments from being sexually harassed

Classical geometry to quantum behavior correspondence in a virtual extra dimension

NASA Astrophysics Data System (ADS)

Dolce, Donatello

2012-09-01

In the Lorentz invariant formalism of compact space-time dimensions the assumption of periodic boundary conditions represents a consistent semi-classical quantization condition for relativistic fields. In Dolce (2011) [18] we have shown, for instance, that the ordinary Feynman path integral is obtained from the interference between the classical paths with different winding numbers associated with the cyclic dynamics of the field solutions. By means of the boundary conditions, the kinematical information of interactions can be encoded on the relativistic geometrodynamics of the boundary, see Dolce (2012) [8]. Furthermore, such a purely four-dimensional theory is manifestly dual to an extra-dimensional field theory. The resulting correspondence between extra-dimensional geometrodynamics and ordinary quantum behavior can be interpreted in terms of AdS/CFT correspondence. By applying this approach to a simple Quark-Gluon-Plasma freeze-out model we obtain fundamental analogies with basic aspects of AdS/QCD phenomenology.

Acquired fears reflected in cortical sensory processing: A review of electrophysiological studies of human classical conditioning

PubMed Central

Miskovic, Vladimir; Keil, Andreas

2012-01-01

The capacity to associate neutral stimuli with affective value is an important survival strategy that can be accomplished by cell assemblies obeying Hebbian learning principles. In the neuroscience laboratory, classical fear conditioning has been extensively used as a model to study learning related changes in neural structure and function. Here, we review the effects of classical fear conditioning on electromagnetic brain activity in humans, focusing on how sensory systems adapt to changing fear-related contingencies. By considering spatio-temporal patterns of mass neuronal activity we illustrate a range of cortical changes related to a retuning of neuronal sensitivity to amplify signals consistent with fear-associated stimuli at the cost of other sensory information. Putative mechanisms that may underlie fear-associated plasticity at the level of the sensory cortices are briefly considered and several avenues for future work are outlined. PMID:22891639

M1 homeopathic complex trigger effective responses against Leishmania (L) amazonensis in vivo and in vitro.

PubMed

Nascimento, Katia Fialho; de Santana, Fabiana Rodrigues; da Costa, Cleber Rafael Vieira; Kaplum, Vanessa; Volpato, Helito; Nakamura, Celso Vaturo; Bonamin, Leoni Villano; de Freitas Buchi, Dorly

2017-11-01

Leishmaniasis is a term referring to a range of clinical conditions caused by protozoan parasites of the genus Leishmania, Trypanosomatidae family, Kinetoplastida order that is transmitted by the bite of certain species of mosquitoes Phlebotominae subfamily. These parasites infect hosts wild and domestic mammals, considered as natural reservoirs and can also infect humans. Leishmania are obligate intramacrophage protozoa that have exclusively intracellular life style. This suggests that the amastigotes possess mechanisms to avoid killing by host cells. Cutaneous leishmaniasis, the most common form of the disease, causes ulcers on exposed parts of the body, leading to disfigurement, permanent scars, and stigma and in some cases disability. Many studies concluded that the cytokines profile and immune system of host have fundamental role in humans and animals natural self-healing. Conventional treatments are far from ideals and the search for new therapeutic alternatives is considered a strategic priority line of research by the World Health Organization. A promising approach in the field of basic research in homeopathy is the treatment of experimental infections with homeopathic drugs prepared from natural substances associations highly diluted, which comprise a combination of several different compounds considered as useful for a symptom or disease. Therefore, this study aimed to evaluate the effect of M1, a complex homeopathic product, in macrophage-Leishmania interaction in vitro and in vivo. It was used RAW cells lineage and BALB/c mice as a host for the promastigotes of L. amazonensis (WHOM/BR/75/Josefa). Several biochemical and morphological parameters were determined. Together, the harmonic results obtained in this study indicate that, in general, the highly diluted products trigger rapid and effective responses by living organisms, cells and mice, against Leishmania, by altering cytokines profile, by NO increasing (p<0.05), by decreasing parasitic load (p<0.001), and modifying classical maturation and biogenesis of parasitophorous vacuoles (p<0.001). M1 complex decreased endocytic index (p<0.001), and the % of infected macrophages (p<0.05), preventing the development of lesions (p<0.05) caused by L. amazonensis by increasing Th1 response (p<0.05). Therefore the M1complex can be a good candidate for a complementary therapy to conventional treatments, since all the parameters observed in vitro and in vivo improved. It could be an interesting clinical tool in association to a classical anti-parasitic treatment, maybe resulting in better quality of life to the patients, with less toxicity. Copyright © 2017 Elsevier Ltd. All rights reserved.

Non-classic multiscale modeling of manipulation based on AFM, in aqueous and humid ambient

NASA Astrophysics Data System (ADS)

Korayem, M. H.; Homayooni, A.; Hefzabad, R. N.

2018-05-01

To achieve a precise manipulation, it is important that an accurate model consisting the size effect and environmental conditions be employed. In this paper, the non-classical multiscale modeling is developed to investigate the manipulation in a vacuum, aqueous and humid ambient. The manipulation structure is considered into two parts as a macro-field (MF) and a nano-field (NF). The governing equations of the AFM components (consist of the cantilever and tip) in the MF are derived based on the modified couple stress theory. The material length scale parameter is used to study the size effect. The fluid flow in the MF is assumed as the Couette and Creeping flows. Moreover, the NF is modeled using the molecular dynamics. The Electro-Based (ELBA) model is considered to model the ambient condition in the NF. The nanoparticle in the different conditions is taken into account to study the manipulation. The results of the manipulation indicate that the predicted deflection of the non-classical model is less than the classical one. Comparison of the nanoparticle travelled distance on substrate shows that the manipulation in the submerged condition is close to the ideal manipulation. The results of humid condition illustrate that by increasing the relative humidity (RH) the manipulation force decreases. Furthermore, Root Mean Square (RMS) as a criterion of damage demonstrates that the submerged nanoparticle has the minimum damage, however, the minimum manipulation force occurs in superlative humid ambient.

Pregnancy and delivery after in vitro maturation of naked ICSI-GV oocytes with GH and transfer of a frozen thawed blastocyst: case report.

PubMed

Menezo, Yves J R; Nicollet, Bernard; Rollet, Jacques; Hazout, André

2006-01-01

To determine if GV oocytes, collected at the time of ICSI, can be matured in vitro and rescued for therapeutic treatment. A patient for whom all the collected oocytes at the GV stage after a classical COH protocol were matured in vitro with GH. All the naked oocytes were matured in a culture medium (ISM2) containing 15% patient serum +1.6 units of GH (Saizen) per millilitre. Oocytes were incubated overnight at 37 degrees C. The MII oocytes obtained were micro-injected. A fresh transfer was performed and a supernumerary blastocyst was frozen. The patient was pregnant and delivered a healthy girl after transfer of the frozen/thawed blastocyst. The baby girl is now 2 years old. In vitro maturation with GH allows rescuing naked GV oocytes collected at the time of ICSI. GH action does not pass through the cumulus cells. According to the possible lack of synchrony between the embryo and the uterus, we recommend to freeze the embryos obtained and to replace them in a controlled cycle.

Cytotoxicity screening of 23 engineered nanomaterials using a test matrix of ten cell lines and three different assays

PubMed Central

2011-01-01

Background Engineered nanomaterials display unique properties that may have impact on human health, and thus require a reliable evaluation of their potential toxicity. Here, we performed a standardized in vitro screening of 23 engineered nanomaterials. We thoroughly characterized the physicochemical properties of the nanomaterials and adapted three classical in vitro toxicity assays to eliminate nanomaterial interference. Nanomaterial toxicity was assessed in ten representative cell lines. Results Six nanomaterials induced oxidative cell stress while only a single nanomaterial reduced cellular metabolic activity and none of the particles affected cell viability. Results from heterogeneous and chemically identical particles suggested that surface chemistry, surface coating and chemical composition are likely determinants of nanomaterial toxicity. Individual cell lines differed significantly in their response, dependent on the particle type and the toxicity endpoint measured. Conclusion In vitro toxicity of the analyzed engineered nanomaterials cannot be attributed to a defined physicochemical property. Therefore, the accurate identification of nanomaterial cytotoxicity requires a matrix based on a set of sensitive cell lines and in vitro assays measuring different cytotoxicity endpoints. PMID:21345205

Nuclear translocation of glutathione S-transferase {pi} is mediated by a non-classical localization signal

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

Kawakatsu, Miho; Goto, Shinji, E-mail: sgoto@nagasaki-u.ac.jp; Yoshida, Takako

2011-08-12

Highlights: {yields} Nuclear translocation of GST{pi} is abrogated by the deletion of the last 16 amino acid residues in the carboxy-terminal region, indicating that residues 195-208 of GST{pi} are required for nuclear translocation. {yields} The lack of a contiguous stretch of positively charged amino acid residues within the carboxy-terminal region of GST{pi}, suggests that the nuclear translocation of GST{pi} is mediated by a non-classical nuclear localization signal. {yields} An in vitro transport assay shows that the nuclear translocation of GST{pi} is dependent on cytosolic factors and ATP. -- Abstract: Glutathione S-transferase {pi} (GST{pi}), a member of the GST family ofmore » multifunctional enzymes, is highly expressed in human placenta and involved in the protection of cellular components against electrophilic compounds or oxidative stress. We have recently found that GST{pi} is expressed in the cytoplasm, mitochondria, and nucleus in some cancer cells, and that the nuclear expression of GST{pi} appears to correlate with resistance to anti-cancer drugs. Although the mitochondrial targeting signal of GST{pi} was previously identified in the amino-terminal region, the mechanism of nuclear translocation remains completely unknown. In this study, we find that the region of GST{pi}195-208 is critical for nuclear translocation, which is mediated by a novel and non-classical nuclear localization signal. In addition, using an in vitro transport assay, we demonstrate that the nuclear translocation of GST{pi} depends on the cytosolic extract and ATP. Although further experiments are needed to understand in depth the precise mechanism of nuclear translocation of GST{pi}, our results may help to establish more efficient anti-cancer therapy, especially with respect to resistance to anti-cancer drugs.« less

ELAC (3,12-di-O-acetyl-8-O-tigloilingol), a plant-derived lathyrane diterpene, induces subventricular zone neural progenitor cell proliferation through PKCβ activation.

PubMed

Murillo-Carretero, Maribel; Geribaldi-Doldán, Noelia; Flores-Giubi, Eugenia; García-Bernal, Francisco; Navarro-Quiroz, Elkin A; Carrasco, Manuel; Macías-Sánchez, Antonio J; Herrero-Foncubierta, Pilar; Delgado-Ariza, Antonio; Verástegui, Cristina; Domínguez-Riscart, Jesús; Daoubi, Mourad; Hernández-Galán, Rosario; Castro, Carmen

2017-07-01

Pharmacological strategies aimed to facilitate neuronal renewal in the adult brain, by promoting endogenous neurogenesis, constitute promising therapeutic options for pathological or traumatic brain lesions. We have previously shown that non-tumour-promoting PKC-activating compounds (12-deoxyphorbols) promote adult neural progenitor cell (NPC) proliferation in vitro and in vivo, enhancing the endogenous neurogenic response of the brain to a traumatic injury. Here, we show for the first time that a diterpene with a lathyrane skeleton can also activate PKC and promote NPC proliferation. We isolated four lathyranes from the latex of Euphorbia plants and tested their effect on postnatal NPC proliferation, using neurosphere cultures. The bioactive lathyrane ELAC (3,12-di-O-acetyl-8-O-tigloilingol) was also injected into the ventricles of adult mice to analyse its effect on adult NPC proliferation in vivo. The lathyrane ELAC activated PKC and significantly increased postnatal NPC proliferation in vitro, particularly in synergy with FGF2. In addition ELAC stimulated proliferation of NPC, specifically affecting undifferentiated transit amplifying cells. The proliferative effect of ELAC was reversed by either the classical/novel PKC inhibitor Gö6850 or the classical PKC inhibitor Gö6976, suggesting that NPC proliferation is promoted in response to activation of classical PKCs, particularly PKCß. ELAC slightly increased the proportion of NPC expressing Sox2. The effects of ELAC disappeared upon acetylation of its C7-hydroxyl group. We propose lathyranes like ELAC as new drug candidates to modulate adult neurogenesis through PKC activation. Functional and structural comparisons between ELAC and phorboids are included. © 2017 The British Pharmacological Society.

Reduction in spontaneous firing of mouse excitatory layer 4 cortical neurons following visual classical conditioning

NASA Astrophysics Data System (ADS)

Bekisz, Marek; Shendye, Ninad; Raciborska, Ida; Wróbel, Andrzej; Waleszczyk, Wioletta J.

2017-08-01

The process of learning induces plastic changes in neuronal network of the brain. Our earlier studies on mice showed that classical conditioning in which monocular visual stimulation was paired with an electric shock to the tail enhanced GABA immunoreactivity within layer 4 of the monocular part of the primary visual cortex (V1), contralaterally to the stimulated eye. In the present experiment we investigated whether the same classical conditioning paradigm induces changes of neuronal excitability in this cortical area. Two experimental groups were used: mice that underwent 7-day visual classical conditioning and controls. Patch-clamp whole-cell recordings were performed from ex vivo slices of mouse V1. The slices were perfused with the modified artificial cerebrospinal fluid, the composition of which better mimics the brain interstitial fluid in situ and induces spontaneous activity. The neuronal excitability was characterized by measuring the frequency of spontaneous action potentials. We found that layer 4 star pyramidal cells located in the monocular representation of the "trained" eye in V1 had lower frequency of spontaneous activity in comparison with neurons from the same cortical region of control animals. Weaker spontaneous firing indicates decreased general excitability of star pyramidal neurons within layer 4 of the monocular representation of the "trained" eye in V1. Such effect could result from enhanced inhibitory processes accompanying learning in this cortical area.

Conditionally prepared photon and quantum imaging

NASA Astrophysics Data System (ADS)

Lvovsky, Alexander I.; Aichele, Thomas

2004-10-01

We discuss a classical model allowing one to visualize and characterize the optical mode of the single photon generated by means of a conditional measurement on a biphoton produced in parametric down-conversion. The model is based on Klyshko's advanced wave interpretation, but extends beyond it, providing a precise mathematical description of the advanced wave. The optical mode of the conditional photon is shown to be identical to the mode of the classical difference-frequency field generated due to nonlinear interaction of the partially coherent advanced wave with the pump pulse. With this "nonlinear advanced wave model" most coherence properties of the conditional photon become manifest, which permits one to intuitively understand many recent results, in particular, in quantum imaging.

Necessary and sufficient conditions on n-qudit state for perfect teleportation of an arbitrary single qudit state

NASA Astrophysics Data System (ADS)

Shang-Guan, Li-Ying; Sun, Hong-Xiang; Wen, Qiao-Yan; Zhu, Fu-Chen

2009-12-01

Firstly, we investigate the necessary and sufficient conditions that an entangled channel of n-qubits should satisfy to carry out perfect teleportation of an arbitrary single qubit state and dense coding. It is shown that the sender can transmit two classical bits of information by sending one qubit. Further, the case of high-dimension quantum state is also considered. Utilizing n-qudit state as quantum channel, it is proposed that the necessary and sufficient conditions are {(d+2)(d-1)}/{2} in all to teleport an arbitrary single qudit state. The sender can transmit 2log2d classical bits of information to the receiver conditioned on the constraints.

Zebrafish model systems for developmental neurobehavioral toxicology.

PubMed

Bailey, Jordan; Oliveri, Anthony; Levin, Edward D

2013-03-01

Zebrafish offer many advantages that complement classic mammalian models for the study of normal development as well as for the teratogenic effects of exposure to hazardous compounds. The clear chorion and embryo of the zebrafish allow for continuous visualization of the anatomical changes associated with development, which, along with short maturation times and the capability of complex behavior, makes this model particularly useful for measuring changes to the developing nervous system. Moreover, the rich array of developmental, behavioral, and molecular benefits offered by the zebrafish have contributed to an increasing demand for the use of zebrafish in behavioral teratology. Essential for this endeavor has been the development of a battery of tests to evaluate a spectrum of behavior in zebrafish. Measures of sensorimotor plasticity, emotional function, cognition and social interaction have been used to characterize the persisting adverse effects of developmental exposure to a variety of chemicals including therapeutic drugs, drugs of abuse and environmental toxicants. In this review, we present and discuss such tests and data from a range of developmental neurobehavioral toxicology studies using zebrafish as a model. Zebrafish provide a key intermediate model between high throughput in vitro screens and the classic mammalian models as they have the accessibility of in vitro models and the complex functional capabilities of mammalian models. Copyright © 2013 Wiley Periodicals, Inc.

Propagation of classical swine fever virus in vitro circumventing heparan sulfate-adaptation.

PubMed

Eymann-Häni, Rita; Leifer, Immanuel; McCullough, Kenneth C; Summerfield, Artur; Ruggli, Nicolas

2011-09-01

Amplification of natural virus isolates in permanent cell lines can result in adaptation, in particular enhanced binding to heparan sulfate (HS)-containing glycosaminoglycans present on most vertebrate cells. This has been reported for several viruses, including the pestivirus classical swine fever virus (CSFV), the causative agent of a highly contagious hemorrhagic disease in pigs. Propagation of CSFV in cell culture is essential in virus diagnostics and research. Adaptation of CSFV to HS-binding has been related to amino acid changes in the viral E(rns) glycoprotein, resulting in viruses with altered replication characteristics in vitro and in vivo. Consequently, a compound blocking the HS-containing structures on cell surfaces was employed to monitor conversion from HS-independency to HS-dependency. It was shown that the porcine PEDSV.15 cell line permitted propagation of CSFV within a limited number of passages without adaptation to HS-binding. The selection of HS-dependent CSFV mutants was also prevented by propagation of the virus in the presence of DSTP 27. The importance of these findings can be seen from the altered ratio of cell-associated to secreted virus upon acquisition of enhanced HS-binding affinity, a phenotype proposed previously to be related to virulence in the natural host. Copyright © 2011 Elsevier B.V. All rights reserved.

Zebrafish Model Systems for Developmental Neurobehavioral Toxicology

PubMed Central

Bailey, Jordan; Oliveri, Anthony; Levin, Edward D.

2014-01-01

Zebrafish offer many advantages that complement classic mammalian models for the study of normal development as well as for the teratogenic effects of exposure to hazardous compounds. The clear chorion and embryo of the zebrafish allow for continuous visualization of the anatomical changes associated with development, which, along with short maturation times and the capability of complex behavior, makes this model particularly useful for measuring changes to the developing nervous system. Moreover, the rich array of developmental, behavioral, and molecular benefits offered by the zebrafish have contributed to an increasing demand for the use of zebrafish in behavioral teratology. Essential for this endeavor has been the development of a battery of tests to evaluate a spectrum of behavior in zebrafish. Measures of sensorimotor plasticity, emotional function, cognition and social interaction have been used to characterize the persisting adverse effects of developmental exposure to a variety of chemicals including therapeutic drugs, drugs of abuse and environmental toxicants. In this review, we present and discuss such tests and data from a range of developmental neurobehavioral toxicology studies using zebrafish as a model. Zebrafish provide a key intermediate model between high throughput in vitro screens and the classic mammalian models as they have the accessibility of in vitro models and the complex functional capabilities of mammalian models. PMID:23723169

Eyeblink conditioning in the developing rabbit

PubMed Central

Brown, Kevin L.; Woodruff-Pak, Diana S.

2011-01-01

Eyeblink classical conditioning in pre-weanling rabbits was examined in the present study. Using a custom lightweight headpiece and restrainer, New Zealand white littermates were trained once daily in 400 ms delay eyeblink classical conditioning from postnatal days (PD) 17–21 or PD 24–28. These ages were chosen because eyeblink conditioning emerges gradually over PD 17–24 in rats (Stanton, Freeman, & Skelton, 1992), another altricial species with neurodevelopmental features similar to those of rabbits. Consistent with well-established findings in rats, rabbits trained from PD 24–28 showed greater conditioning relative to littermates trained from PD 17–21. Both age groups displayed poor retention of eyeblink conditioning at retraining one month after acquisition. These findings are the first to demonstrate eyeblink conditioning in the developing rabbit. With further characterization of optimal conditioning parameters, this preparation may have applications to neurodevelopmental disease models as well as research exploring the ontogeny of memory. PMID:21953433

Classical analogous of quantum cosmological perfect fluid models

NASA Astrophysics Data System (ADS)

Batista, A. B.; Fabris, J. C.; Gonçalves, S. V. B.; Tossa, J.

2001-05-01

Quantization in the minisuperspace of a gravity system coupled to a perfect fluid, leads to a solvable model which implies singularity free solutions through the construction of a superposition of the wavefunctions. We show that such models are equivalent to a classical system where, besides the perfect fluid, a repulsive fluid with an equation of state pQ= ρQ is present. This leads to speculate on the true nature of this quantization procedure. A perturbative analysis of the classical system reveals the condition for the stability of the classical system in terms of the existence of an anti-gravity phase.

Non-classical and potential symmetry analysis of Richard's equation for moisture flow in soil

NASA Astrophysics Data System (ADS)

Wiltshire, Ron; El-Kafri, Manal

2004-01-01

This paper focuses upon the derivation of the non-classical symmetries of Bluman and Cole as they apply to Richard's equation for water flow in an unsaturated uniform soil. It is shown that the determining equations for the non-classical case lead to four highly non-linear equations which have been solved in five particular cases. In each case the corresponding similarity ansatz has been derived and Richard's equation is reduced to an ordinary differential equation. Explicit solutions are produced when possible. Richard's equation is also expressed as a potential system and in reviewing the classical Lie solutions a new symmetry is derived together with its similarity ansatz. Determining equations are then produced for the potential system using the non-classical algorithm. This results in an under-determined set of equations and an example symmetry that reveals a missing classical case is presented. An example of a classical and a non-classical symmetry reduction applied to the infiltration of moisture in soil is presented. The condition for surface invariance is used to demonstrate the equivalence of a classical Lie and a potential symmetry.

Effect of circadian phase on memory acquisition and recall: operant conditioning vs. classical conditioning.

PubMed

Garren, Madeleine V; Sexauer, Stephen B; Page, Terry L

2013-01-01

There have been several studies on the role of circadian clocks in the regulation of associative learning and memory processes in both vertebrate and invertebrate species. The results have been quite variable and at present it is unclear to what extent the variability observed reflects species differences or differences in methodology. Previous results have shown that following differential classical conditioning in the cockroach, Rhyparobia maderae, in an olfactory discrimination task, formation of the short-term and long-term memory is under strict circadian control. In contrast, there appeared to be no circadian regulation of the ability to recall established memories. In the present study, we show that following operant conditioning of the same species in a very similar olfactory discrimination task, there is no impact of the circadian system on either short-term or long-term memory formation. On the other hand, ability to recall established memories is strongly tied to the circadian phase of training. On the basis of these data and those previously reported for phylogenetically diverse species, it is suggested that there may be fundamental differences in the way the circadian system regulates learning and memory in classical and operant conditioning.

Effect of Circadian Phase on Memory Acquisition and Recall: Operant Conditioning vs. Classical Conditioning

PubMed Central

Garren, Madeleine V.; Sexauer, Stephen B.; Page, Terry L.

2013-01-01

There have been several studies on the role of circadian clocks in the regulation of associative learning and memory processes in both vertebrate and invertebrate species. The results have been quite variable and at present it is unclear to what extent the variability observed reflects species differences or differences in methodology. Previous results have shown that following differential classical conditioning in the cockroach, Rhyparobia maderae, in an olfactory discrimination task, formation of the short-term and long-term memory is under strict circadian control. In contrast, there appeared to be no circadian regulation of the ability to recall established memories. In the present study, we show that following operant conditioning of the same species in a very similar olfactory discrimination task, there is no impact of the circadian system on either short-term or long-term memory formation. On the other hand, ability to recall established memories is strongly tied to the circadian phase of training. On the basis of these data and those previously reported for phylogenetically diverse species, it is suggested that there may be fundamental differences in the way the circadian system regulates learning and memory in classical and operant conditioning. PMID:23533587

Rapid learning dynamics in individual honeybees during classical conditioning.

PubMed

Pamir, Evren; Szyszka, Paul; Scheiner, Ricarda; Nawrot, Martin P

2014-01-01

Associative learning in insects has been studied extensively by a multitude of classical conditioning protocols. However, so far little emphasis has been put on the dynamics of learning in individuals. The honeybee is a well-established animal model for learning and memory. We here studied associative learning as expressed in individual behavior based on a large collection of data on olfactory classical conditioning (25 datasets, 3298 animals). We show that the group-averaged learning curve and memory retention score confound three attributes of individual learning: the ability or inability to learn a given task, the generally fast acquisition of a conditioned response (CR) in learners, and the high stability of the CR during consecutive training and memory retention trials. We reassessed the prevailing view that more training results in better memory performance and found that 24 h memory retention can be indistinguishable after single-trial and multiple-trial conditioning in individuals. We explain how inter-individual differences in learning can be accommodated within the Rescorla-Wagner theory of associative learning. In both data-analysis and modeling we demonstrate how the conflict between population-level and single-animal perspectives on learning and memory can be disentangled.

Rapid learning dynamics in individual honeybees during classical conditioning

PubMed Central

Pamir, Evren; Szyszka, Paul; Scheiner, Ricarda; Nawrot, Martin P.

2014-01-01

Associative learning in insects has been studied extensively by a multitude of classical conditioning protocols. However, so far little emphasis has been put on the dynamics of learning in individuals. The honeybee is a well-established animal model for learning and memory. We here studied associative learning as expressed in individual behavior based on a large collection of data on olfactory classical conditioning (25 datasets, 3298 animals). We show that the group-averaged learning curve and memory retention score confound three attributes of individual learning: the ability or inability to learn a given task, the generally fast acquisition of a conditioned response (CR) in learners, and the high stability of the CR during consecutive training and memory retention trials. We reassessed the prevailing view that more training results in better memory performance and found that 24 h memory retention can be indistinguishable after single-trial and multiple-trial conditioning in individuals. We explain how inter-individual differences in learning can be accommodated within the Rescorla–Wagner theory of associative learning. In both data-analysis and modeling we demonstrate how the conflict between population-level and single-animal perspectives on learning and memory can be disentangled. PMID:25309366

The search for the engram in eyeblink conditioning: A synopsis of past and present perspectives on the role of the cerebellum.

PubMed

Foy, Michael R; Foy, Judith G

2016-12-01

One of the most prolific behavioral neuroscientists of his generation, Richard F. Thompson published more than 450 research articles during his almost 60-year career before his death in 2014. The breadth and reach of his scholarship has extended to a large multidisciplinary audience of scientists. The focal point of this article is arguably his most influential paper on cerebellar classical conditioning entitled "The Neurobiology of Learning and Memory" that appeared in Science in 1986 and has been cited 700 times since its publication. Here, a summary of the initial Thompson laboratory research leading up to an understanding of the cerebellum and its critical role in memory traces will be discussed, along with conclusions from the Science article pertinent to cerebellar classical conditioning. The summary will also discuss how the original 1986 article continues to stimulate and influence new research and provide further insights into the role of the cerebellum in the neurobiology of learning and memory function relevant to studies of mammalian classical conditioning. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Feasibility of a transient elastography technique for in vitro arterial elasticity assessment.

PubMed

Brum, J; Balay, G; Bia, D; Armentano, R L; Negreira, C

2010-01-01

The early detection of biomechanical modifications in the arterial wall could be used as a predictor factor for various diseases, for example hypertension or atherosclerosis. In this work a transient elastography technique is used for the in vitro evaluation of the arterial wall elasticity. The obtained Young modulus is compared with the one obtained by a more classical approach: pressure-diameter relationships. As a sample an arterial phantom made of PolyVinyl Alcohol (PVA) gel was used. Diameter variation due to pressure variation inside the phantom was recorded by means of ultrasound. Through both techniques similar Young modulus estimations are obtained showing in this way the feasibility of applying transient elastography for the arterial wall elasticity assessment.

Quantum localization for a kicked rotor with accelerator mode islands.

PubMed

Iomin, A; Fishman, S; Zaslavsky, G M

2002-03-01

Dynamical localization of classical superdiffusion for the quantum kicked rotor is studied in the semiclassical limit. Both classical and quantum dynamics of the system become more complicated under the conditions of mixed phase space with accelerator mode islands. Recently, long time quantum flights due to the accelerator mode islands have been found. By exploration of their dynamics, it is shown here that the classical-quantum duality of the flights leads to their localization. The classical mechanism of superdiffusion is due to accelerator mode dynamics, while quantum tunneling suppresses the superdiffusion and leads to localization of the wave function. Coupling of the regular type dynamics inside the accelerator mode island structures to dynamics in the chaotic sea proves increasing the localization length. A numerical procedure and an analytical method are developed to obtain an estimate of the localization length which, as it is shown, has exponentially large scaling with the dimensionless Planck's constant (tilde)h<1 in the semiclassical limit. Conditions for the validity of the developed method are specified.

Entanglement conservation, ER=EPR, and a new classical area theorem for wormholes

DOE PAGES

Remmen, Grant N.; Bao, Ning; Pollack, Jason

2016-07-11

We consider the question of entanglement conservation in the context of the ER=EPR correspondence equating quantum entanglement with wormholes. In quantum mechanics, the entanglement between a system and its complement is conserved under unitary operations that act independently on each; ER=EPR suggests that an analogous statement should hold for wormholes. We accordingly prove a new area theorem in general relativity: for a collection of dynamical wormholes and black holes in a spacetime satisfying the null curvature condition, the maximin area for a subset of the horizons (giving the largest area attained by the minimal cross section of the multi-wormhole throatmore » separating the subset from its complement) is invariant under classical time evolution along the outermost apparent horizons. The evolution can be completely general, including horizon mergers and the addition of classical matter satisfying the null energy condition. In conclusion, this theorem is the gravitational dual of entanglement conservation and thus constitutes an explicit characterization of the ER=EPR duality in the classical limit.« less

Entanglement conservation, ER=EPR, and a new classical area theorem for wormholes

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

Remmen, Grant N.; Bao, Ning; Pollack, Jason

We consider the question of entanglement conservation in the context of the ER=EPR correspondence equating quantum entanglement with wormholes. In quantum mechanics, the entanglement between a system and its complement is conserved under unitary operations that act independently on each; ER=EPR suggests that an analogous statement should hold for wormholes. We accordingly prove a new area theorem in general relativity: for a collection of dynamical wormholes and black holes in a spacetime satisfying the null curvature condition, the maximin area for a subset of the horizons (giving the largest area attained by the minimal cross section of the multi-wormhole throatmore » separating the subset from its complement) is invariant under classical time evolution along the outermost apparent horizons. The evolution can be completely general, including horizon mergers and the addition of classical matter satisfying the null energy condition. In conclusion, this theorem is the gravitational dual of entanglement conservation and thus constitutes an explicit characterization of the ER=EPR duality in the classical limit.« less

Transport Pathways—Proton Motive Force Interrelationship in Durum Wheat Mitochondria

PubMed Central

Trono, Daniela; Laus, Maura N.; Soccio, Mario; Pastore, Donato

2014-01-01

In durum wheat mitochondria (DWM) the ATP-inhibited plant mitochondrial potassium channel (PmitoKATP) and the plant uncoupling protein (PUCP) are able to strongly reduce the proton motive force (pmf) to control mitochondrial production of reactive oxygen species; under these conditions, mitochondrial carriers lack the driving force for transport and should be inactive. However, unexpectedly, DWM uncoupling by PmitoKATP neither impairs the exchange of ADP for ATP nor blocks the inward transport of Pi and succinate. This uptake may occur via the plant inner membrane anion channel (PIMAC), which is physiologically inhibited by membrane potential, but unlocks its activity in de-energized mitochondria. Probably, cooperation between PIMAC and carriers may accomplish metabolite movement across the inner membrane under both energized and de-energized conditions. PIMAC may also cooperate with PmitoKATP to transport ammonium salts in DWM. Interestingly, this finding may trouble classical interpretation of in vitro mitochondrial swelling; instead of free passage of ammonia through the inner membrane and proton symport with Pi, that trigger metabolite movements via carriers, transport of ammonium via PmitoKATP and that of the counteranion via PIMAC may occur. Here, we review properties, modulation and function of the above reported DWM channels and carriers to shed new light on the control that they exert on pmf and vice-versa. PMID:24821541

Efficient Classical Algorithm for Boson Sampling with Partially Distinguishable Photons

NASA Astrophysics Data System (ADS)

Renema, J. J.; Menssen, A.; Clements, W. R.; Triginer, G.; Kolthammer, W. S.; Walmsley, I. A.

2018-06-01

We demonstrate how boson sampling with photons of partial distinguishability can be expressed in terms of interference of fewer photons. We use this observation to propose a classical algorithm to simulate the output of a boson sampler fed with photons of partial distinguishability. We find conditions for which this algorithm is efficient, which gives a lower limit on the required indistinguishability to demonstrate a quantum advantage. Under these conditions, adding more photons only polynomially increases the computational cost to simulate a boson sampling experiment.

The non-classical MAP kinase ERK3 controls T cell activation.

PubMed

Marquis, Miriam; Boulet, Salix; Mathien, Simon; Rousseau, Justine; Thébault, Paméla; Daudelin, Jean-François; Rooney, Julie; Turgeon, Benjamin; Beauchamp, Claudine; Meloche, Sylvain; Labrecque, Nathalie

2014-01-01

The classical mitogen-activated protein kinases (MAPKs) ERK1 and ERK2 are activated upon stimulation of cells with a broad range of extracellular signals (including antigens) allowing cellular responses to occur. ERK3 is an atypical member of the MAPK family with highest homology to ERK1/2. Therefore, we evaluated the role of ERK3 in mature T cell response. Mouse resting T cells do not transcribe ERK3 but its expression is induced in both CD4⁺ and CD8⁺ T cells following T cell receptor (TCR)-induced T cell activation. This induction of ERK3 expression in T lymphocytes requires activation of the classical MAPK ERK1 and ERK2. Moreover, ERK3 protein is phosphorylated and associates with MK5 in activated primary T cells. We show that ERK3-deficient T cells have a decreased proliferation rate and are impaired in cytokine secretion following in vitro stimulation with low dose of anti-CD3 antibodies. Our findings identify the atypical MAPK ERK3 as a new and important regulator of TCR-induced T cell activation.

The Non-Classical MAP Kinase ERK3 Controls T Cell Activation

PubMed Central

Mathien, Simon; Rousseau, Justine; Thébault, Paméla; Daudelin, Jean-François; Rooney, Julie; Turgeon, Benjamin; Beauchamp, Claudine; Meloche, Sylvain; Labrecque, Nathalie

2014-01-01

The classical mitogen-activated protein kinases (MAPKs) ERK1 and ERK2 are activated upon stimulation of cells with a broad range of extracellular signals (including antigens) allowing cellular responses to occur. ERK3 is an atypical member of the MAPK family with highest homology to ERK1/2. Therefore, we evaluated the role of ERK3 in mature T cell response. Mouse resting T cells do not transcribe ERK3 but its expression is induced in both CD4+ and CD8+ T cells following T cell receptor (TCR)-induced T cell activation. This induction of ERK3 expression in T lymphocytes requires activation of the classical MAPK ERK1 and ERK2. Moreover, ERK3 protein is phosphorylated and associates with MK5 in activated primary T cells. We show that ERK3-deficient T cells have a decreased proliferation rate and are impaired in cytokine secretion following in vitro stimulation with low dose of anti-CD3 antibodies. Our findings identify the atypical MAPK ERK3 as a new and important regulator of TCR-induced T cell activation. PMID:24475167

Meropenem/colistin synergy testing for multidrug-resistant Acinetobacter baumannii strains by a two-dimensional gradient technique applicable in routine microbiology.

PubMed

van Belkum, Alex; Halimi, Diane; Bonetti, Eve-Julie; Renzi, Gesuele; Cherkaoui, Abdessalam; Sauvonnet, Véronique; Martelin, Roland; Durand, Géraldine; Chatellier, Sonia; Zambardi, Gilles; Engelhardt, Anette; Karlsson, Åsa; Schrenzel, Jacques

2015-01-01

Precise assessment of potential therapeutic synergy, antagonism or indifference between antimicrobial agents currently depends on time-consuming and hard-to-standardize in vitro chequerboard titration methods. We here present a method based on a novel two-dimensional antibiotic gradient technique named Xact™. We used a test comprising a combination of perpendicular gradients of meropenem and colistin in a single quadrant. We compared test outcomes with those obtained with classical chequerboard microbroth dilution testing in a study involving 27 unique strains of multidrug-resistant Acinetobacter baumannii from diverse origins. We were able to demonstrate 92% concordance between the new technology and classical chequerboard titration using the A. baumannii collection. Two strains could not be analysed by Xact™ due to their out-of-range MIC of meropenem (>128 mg/L). The new test was shown to be diagnostically useful, easy to implement and less labour intensive than the classical method. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

In Vitro Impact of Conditioned Medium From Demineralized Freeze-Dried Bone on Human Umbilical Endothelial Cells.

PubMed

Harnik, Branko; Miron, Richard J; Buser, Daniel; Gruber, Reinhard

2017-03-01

Angiogenesis is essential for the consolidation of bone allografts. The underlying molecular mechanism, however, remains unclear. Soluble factors released from demineralized freeze-dried bone target mesenchymal cells; however, their effect on endothelial cells has not been investigated so far. The aim of the present study was therefore to examine the effect of conditioned medium from demineralized freeze-dried bone on human umbilical endothelial cells in vitro. Conditioned medium was first prepared from demineralized freeze-dried bone following 24 hours incubation at room temperature to produce demineralized bone conditioned media. Thereafter, conditioned medium was used to stimulate human umbilical vein endothelial cells in vitro by determining the cell response based on viability, proliferation, expression of apoptotic genes, a Boyden chamber to determine cell migration, and the formation of branches. The authors report here that conditioned medium decreased viability and proliferation of endothelial cells. Neither of the apoptotic marker genes was significantly altered when endothelial cells were exposed to conditioned medium. The Boyden chamber revealed that endothelial cells migrate toward conditioned medium. Moreover, conditioned medium moderately stimulated the formation of branches. These findings support the concept that conditioned medium from demineralized freeze-dried bone targets endothelial cells by decreasing their proliferation and enhancing their motility under these in vitro conditions.

Emotional eating and Pavlovian learning: does negative mood facilitate appetitive conditioning?

PubMed

Bongers, Peggy; van den Akker, Karolien; Havermans, Remco; Jansen, Anita

2015-06-01

Emotional eating has been suggested to be a learned behaviour; more specifically, classical conditioning processes might be involved in its development. In the present study we investigated whether a negative mood facilitates appetitive conditioning and whether trait impulsivity influences this process. After undergoing either a negative or neutral mood induction, participants were subjected to a differential classical conditioning procedure, using neutral stimuli and appetizing food. Two initially neutral distinctive vases with flowers were (CS+) or were not (CS-) paired with chocolate mousse intake. We measured participants' expectancy and desire to eat (4 CS+ and 4 CS- trials), salivation response, and actual food intake. The BIS-11 was administered to assess trait impulsivity. In both mood conditions, participants showed a classically conditioned appetite. Unexpectedly, there was no evidence of facilitated appetitive learning in a negative mood with regard to expectancy, desire, salivation, or intake. However, immediately before the taste test, participants in the negative mood condition reported a stronger desire to eat in the CS+ compared to the CS- condition, while no such effect occurred in the neutral group. An effect of impulsivity was found with regard to food intake in the neutral mood condition: high-impulsive participants consumed less food when presented with the CS+ compared to the CS-, and also less than low-impulsive participants. An alternative pathway to appetitive conditioning with regard to emotions is that it is not the neutral stimuli, but the emotions themselves that become conditioned stimuli and elicit appetitive responses. Copyright © 2015 Elsevier Ltd. All rights reserved.

Mycobacterium tuberculosis Maltosyltransferase GlgE, a Genetically Validated Antituberculosis Target, Is Negatively Regulated by Ser/Thr Phosphorylation*

PubMed Central

Leiba, Jade; Syson, Karl; Baronian, Grégory; Zanella-Cléon, Isabelle; Kalscheuer, Rainer; Kremer, Laurent; Bornemann, Stephen; Molle, Virginie

2013-01-01

GlgE is a maltosyltransferase involved in the biosynthesis of α-glucans that has been genetically validated as a potential therapeutic target against Mycobacterium tuberculosis. Despite also making α-glucan, the GlgC/GlgA glycogen pathway is distinct and allosterically regulated. We have used a combination of genetics and biochemistry to establish how the GlgE pathway is regulated. M. tuberculosis GlgE was phosphorylated specifically by the Ser/Thr protein kinase PknB in vitro on one serine and six threonine residues. Furthermore, GlgE was phosphorylated in vivo when expressed in Mycobacterium bovis bacillus Calmette–Guérin (BCG) but not when all seven phosphorylation sites were replaced by Ala residues. The GlgE orthologues from Mycobacterium smegmatis and Streptomyces coelicolor were phosphorylated by the corresponding PknB orthologues in vitro, implying that the phosphorylation of GlgE is widespread among actinomycetes. PknB-dependent phosphorylation of GlgE led to a 2 orders of magnitude reduction in catalytic efficiency in vitro. The activities of phosphoablative and phosphomimetic GlgE derivatives, where each phosphorylation site was substituted with either Ala or Asp residues, respectively, correlated with negative phosphoregulation. Complementation studies of a M. smegmatis glgE mutant strain with these GlgE derivatives, together with both classical and chemical forward genetics, were consistent with flux through the GlgE pathway being correlated with GlgE activity. We conclude that the GlgE pathway appears to be negatively regulated in actinomycetes through the phosphorylation of GlgE by PknB, a mechanism distinct from that known in the classical glycogen pathway. Thus, these findings open new opportunities to target the GlgE pathway therapeutically. PMID:23609448

In Vitro Coinfection and Replication of Classical Swine Fever Virus and Porcine Circovirus Type 2 in PK15 Cells

PubMed Central

Zhou, Niu; Xing, Gang; Zhou, Jianwei; Jin, Yulan; Liang, Cuiqin; Gu, Jinyan; Hu, Boli; Liao, Min; Wang, Qin; Zhou, Jiyong

2015-01-01

Increasing clinical lines of evidence have shown the coinfection/superinfection of porcine circovirus type 2 (PCV2) and classical swine fever virus (CSFV). Here, we investigated whether PCV2 and CSFV could infect the same cell productively by constructing an in vitro coinfection model. Our results indicated that PCV2-free PK15 cells but not ST cells were more sensitive to PCV2, and the PK15 cell line could stably harbor replicating CSFV (PK15-CSFV cells) with a high infection rate. Confocal and super-resolution microscopic analysis showed that PCV2 and CSFV colocalized in the same PK15-CSFV cell, and the CSFV E2 protein translocated from the cytoplasm to the nucleus in PK15-CSFV cells infected with PCV2. Moreover, PCV2-CSFV dual-positive cells increased gradually in PK15-CSFV cells in a PCV2 dose-dependent manner. In PK15-CSFV cells, PCV2 replicated well, and the production of PCV2 progeny was not influenced by CSFV infection. However, CSFV reproduction decreased in a PCV2 dose-dependent manner. In addition, cellular apoptosis was not strengthened in PK15-CSFV cells infected with PCV2 in comparison with PCV2-infected PK15 cells. Moreover, using this coinfection model we further demonstrated PCV2-induced apoptosis might contribute to the impairment of CSFV HCLV strain replication in coinfected cells. Taken together, our results demonstrate for the first time the coinfection/superinfection of PCV2 and CSFV within the same cell, providing an in vitro model to facilitate further investigation of the underlying mechanism of CSFV and PCV2 coinfection. PMID:26431319

Mycobacterium tuberculosis maltosyltransferase GlgE, a genetically validated antituberculosis target, is negatively regulated by Ser/Thr phosphorylation.

PubMed

Leiba, Jade; Syson, Karl; Baronian, Grégory; Zanella-Cléon, Isabelle; Kalscheuer, Rainer; Kremer, Laurent; Bornemann, Stephen; Molle, Virginie

2013-06-07

GlgE is a maltosyltransferase involved in the biosynthesis of α-glucans that has been genetically validated as a potential therapeutic target against Mycobacterium tuberculosis. Despite also making α-glucan, the GlgC/GlgA glycogen pathway is distinct and allosterically regulated. We have used a combination of genetics and biochemistry to establish how the GlgE pathway is regulated. M. tuberculosis GlgE was phosphorylated specifically by the Ser/Thr protein kinase PknB in vitro on one serine and six threonine residues. Furthermore, GlgE was phosphorylated in vivo when expressed in Mycobacterium bovis bacillus Calmette-Guérin (BCG) but not when all seven phosphorylation sites were replaced by Ala residues. The GlgE orthologues from Mycobacterium smegmatis and Streptomyces coelicolor were phosphorylated by the corresponding PknB orthologues in vitro, implying that the phosphorylation of GlgE is widespread among actinomycetes. PknB-dependent phosphorylation of GlgE led to a 2 orders of magnitude reduction in catalytic efficiency in vitro. The activities of phosphoablative and phosphomimetic GlgE derivatives, where each phosphorylation site was substituted with either Ala or Asp residues, respectively, correlated with negative phosphoregulation. Complementation studies of a M. smegmatis glgE mutant strain with these GlgE derivatives, together with both classical and chemical forward genetics, were consistent with flux through the GlgE pathway being correlated with GlgE activity. We conclude that the GlgE pathway appears to be negatively regulated in actinomycetes through the phosphorylation of GlgE by PknB, a mechanism distinct from that known in the classical glycogen pathway. Thus, these findings open new opportunities to target the GlgE pathway therapeutically.

FAST TRACK COMMUNICATION: Necessary conditions for classical super-integrability of a certain family of potentials in constant curvature spaces

NASA Astrophysics Data System (ADS)

Maciejewski, Andrzej J.; Przybylska, Maria; Yoshida, Haruo

2010-09-01

We formulate the necessary conditions for the maximal super-integrability of a certain family of classical potentials defined in the constant curvature two-dimensional spaces. We give examples of homogeneous potentials of degree -2 on {\\bb E}^2 as well as their equivalents on {\\bb S}^2 and {\\bb H}^2 for which these necessary conditions are also sufficient. We show explicit forms of the additional first integrals which can always be chosen as a polynomial with respect to the momenta and which can be of an arbitrary high degree with respect to the momenta.

Modification of Classical SPM for Slightly Rough Surface Scattering with Low Grazing Angle Incidence

NASA Astrophysics Data System (ADS)

Guo, Li-Xin; Wei, Guo-Hui; Kim, Cheyoung; Wu, Zhen-Sen

2005-11-01

Based on the impedance/admittance rough boundaries, the reflection coefficients and the scattering cross section with low grazing angle incidence are obtained for both VV and HH polarizations. The error of the classical perturbation method at grazing angle is overcome for the vertical polarization at a rough Neumann boundary of infinite extent. The derivation of the formulae and the numerical results show that the backscattering cross section depends on the grazing angle to the fourth power for both Neumann and Dirichlet boundary conditions with low grazing angle incidence. Our results can reduce to that of the classical small perturbation method by neglecting the Neumann and Dirichlet boundary conditions. The project supported by National Natural Science Foundation of China under Grant No. 60101001 and the National Defense Foundation of China

Vibrational monitor of early demineralization in tooth enamel after in vitro exposure to phosphoridic liquid

NASA Astrophysics Data System (ADS)

Pezzotti, Giuseppe; Adachi, Tetsuya; Gasparutti, Isabella; Vincini, Giulio; Zhu, Wenliang; Boffelli, Marco; Rondinella, Alfredo; Marin, Elia; Ichioka, Hiroaki; Yamamoto, Toshiro; Marunaka, Yoshinori; Kanamura, Narisato

2017-02-01

The Raman spectroscopic method has been applied to quantitatively assess the in vitro degree of demineralization in healthy human teeth. Based on previous evaluations of Raman selection rules (empowered by an orientation distribution function (ODF) statistical algorithm) and on a newly proposed analysis of phonon density of states (PDOS) for selected vibrational modes of the hexagonal structure of hydroxyapatite, a molecular-scale evaluation of the demineralization process upon in vitro exposure to a highly acidic beverage (i.e., CocaCola™ Classic, pH = 2.5) could be obtained. The Raman method proved quite sensitive and spectroscopic features could be directly related to an increase in off-stoichiometry of the enamel surface structure since the very early stage of the demineralization process (i.e., when yet invisible to other conventional analytical techniques). The proposed Raman spectroscopic algorithm might possess some generality for caries risk assessment, allowing a prompt non-contact diagnostic practice in dentistry.

Synthesis and functional characterization of novel derivatives related to oxotremorine and oxotremorine-M.

PubMed

Dallanoce, C; Conti, P; De Amici, M; De Micheli, C; Barocelli, E; Chiavarini, M; Ballabeni, V; Bertoni, S; Impicciatore, M

1999-08-01

Two subseries of nonquaternized (5a-10a) and quaternized derivatives (5b-10b) related to oxotremorine and oxotremorine-M were synthesized and tested. The agonist potency at the muscarinic receptor subtypes of the new compounds was estimated in three classical in vitro functional assays: M1 rabbit vas deferens, M2 guinea pig left atrium and M3 guinea pig ileum. In addition, the occurrence of central muscarinic effects was evaluated as tremorigenic activity after intraperitoneal administration in mice. In in vitro tests a nonselective muscarinic activity was exhibited by all the derivatives with potencies values that, in some instances, surpassed those of the reference compounds (i.e. 8b). Functional selectivity was evidenced only for the oxotremorine-like derivative 9a, which behaved as a mixed M3-agonist/M1-antagonist (pD2 = 5.85; pA2 = 4.76, respectively). In in vivo tests non-quaternary compounds were able to evoke central muscarinic effects, with a potency order parallel to that observed in vitro.

Comparison of learning curves and skill transfer between classical and robotic laparoscopy according to the viewing conditions: implications for training.

PubMed

Blavier, Adélaïde; Gaudissart, Quentin; Cadière, Guy-Bernard; Nyssen, Anne-Sophie

2007-07-01

The purpose of this study was to evaluate the perceptual (2-dimensional [2D] vs. 3-dimensional [3D] view) and instrumental (classical vs. robotic) impacts of new robotic system on learning curves. Forty medical students without any surgical experience were randomized into 4 groups (classical laparoscopy with 3D-direct view or with 2D-indirect view, robotic system in 3D or in 2D) and repeated a laparoscopic task 6 times. After these 6 repetitions, they performed 2 trials with the same technique but in the other viewing condition (perceptive switch). Finally, subjects performed the last 3 trials with the technique they never used (technical switch). Subjects evaluated their performance answering a questionnaire (impressions of mastery, familiarity, satisfaction, self-confidence, and difficulty). Our study showed better performance and improvement in 3D view than in 2D view whatever the instrumental aspect. Participants reported less mastery, familiarity, and self-confidence and more difficulty in classical laparoscopy with 2D-indirect view than in the other conditions. Robotic surgery improves surgical performance and learning, particularly by 3D view advantage. However, perceptive and technical switches emphasize the need to adapt and pursue training also with traditional technology to prevent risks in conversion procedure.

Quantum to classical transition in the Hořava-Lifshitz quantum cosmology

NASA Astrophysics Data System (ADS)

Bernardini, A. E.; Leal, P.; Bertolami, O.

2018-02-01

A quasi-Gaussian quantum superposition of Hořava-Lifshitz (HL) stationary states is built in order to describe the transition of the quantum cosmological problem to the related classical dynamics. The obtained HL phase-space superposed Wigner function and its associated Wigner currents describe the conditions for the matching between classical and quantum phase-space trajectories. The matching quantum superposition parameter is associated to the total energy of the classical trajectory which, at the same time, drives the engendered Wigner function to the classical stationary regime. Through the analysis of the Wigner flows, the quantum fluctuations that distort the classical regime can be quantified as a measure of (non)classicality. Finally, the modifications to the Wigner currents due to the inclusion of perturbative potentials are computed in the HL quantum cosmological context. In particular, the inclusion of a cosmological constant provides complementary information that allows for connecting the age of the Universe with the overall stiff matter density profile.

Classical conditioning of sexual response in women: a replication study.

PubMed

Both, Stephanie; Brauer, Marieke; Laan, Ellen

2011-11-01

According to incentive motivation models, sexual stimuli play a crucial role in eliciting sexual arousal, desire, and behavior. Therefore, it seems highly valuable to investigate the process through which stimuli acquire motivational value. Although many theories of human sexual behavior assume that sexual stimuli obtain arousing properties through classical conditioning, systematic research on classical conditioning of sexual responses in humans is scarce. Recently, however, our research group observed conditioned genital responses in women using a differential conditioning procedure and genital vibrostimulation as unconditional stimulus (US). The aim of the present experiment was to perform an extended replication of this previous study to test the efficacy of our conditioning paradigm. A differential conditioning experiment was conducted in 32 sexually functional women. Neutral pictures served as conditional stimuli (CSs) and genital vibrostimulation as US. Only one CS (the CS+) was followed by the US during the acquisition phase. Conditioned responses were assessed during the extinction phase. Vaginal pulse amplitude (VPA) and skin conductance level were assessed, and ratings of affective value and sexual arousal were obtained. As expected, during the extinction phase, VPA was higher in response to the CS+ than to the CS-. Also, the CS+ tended to be evaluated as more positive and as more sexually arousing than the CS-. In addition, the magnitude of conditioned subjective affect was related to scores on the Sexual Inhibition\\Sexual Excitation Scales. Skin conductance levels showed no conditioning effect. Genital and subjective sexual responses were successfully modulated by the differential conditioning paradigm. This replication of our previous study confirms the effectiveness of our conditioning procedure and indicates that it may provide a fruitful paradigm for further research on associative sexual reward learning in humans. © 2011 International Society for Sexual Medicine.

Classical Affine W-Algebras and the Associated Integrable Hamiltonian Hierarchies for Classical Lie Algebras

NASA Astrophysics Data System (ADS)

De Sole, Alberto; Kac, Victor G.; Valeri, Daniele

2018-06-01

We prove that any classical affine W-algebra W (g, f), where g is a classical Lie algebra and f is an arbitrary nilpotent element of g, carries an integrable Hamiltonian hierarchy of Lax type equations. This is based on the theories of generalized Adler type operators and of generalized quasideterminants, which we develop in the paper. Moreover, we show that under certain conditions, the product of two generalized Adler type operators is a Lax type operator. We use this fact to construct a large number of integrable Hamiltonian systems, recovering, as a special case, all KdV type hierarchies constructed by Drinfeld and Sokolov.

Random walk in generalized quantum theory

NASA Astrophysics Data System (ADS)

Martin, Xavier; O'Connor, Denjoe; Sorkin, Rafael D.

2005-01-01

One can view quantum mechanics as a generalization of classical probability theory that provides for pairwise interference among alternatives. Adopting this perspective, we “quantize” the classical random walk by finding, subject to a certain condition of “strong positivity”, the most general Markovian, translationally invariant “decoherence functional” with nearest neighbor transitions.

Ontogeny of Classical and Operant Learning Behaviors in Zebrafish

ERIC Educational Resources Information Center

Valente, Andre; Huang, Kuo-Hua; Portugues, Ruben; Engert, Florian

2012-01-01

The performance of developing zebrafish in both classical and operant conditioning assays was tested with a particular focus on the emergence of these learning behaviors during development. Strategically positioned visual cues paired with electroshocks were used in two fully automated assays to investigate both learning paradigms. These allow the…

In-Service Training of Teachers as Behavior Modifiers: Review and Analysis.

ERIC Educational Resources Information Center

Eachus, Herbert Todd

The basic principles of operant and classical conditioning are presented, and their applications for the in-service training of teachers are discussed. Certain classroom behaviors are analyzed and applied to the classic stimulus-response paradigm. Activities are generically classified as positive or negative reinforcers and these reinforcers, in…

Differentiating aversive conditioning in bistable perception: Avoidance of a percept vs. salience of a stimulus.

PubMed

Wilbertz, Gregor; Sterzer, Philipp

2018-05-01

Alternating conscious visual perception of bistable stimuli is influenced by several factors. In order to understand the effect of negative valence, we tested the effect of two types of aversive conditioning on dominance durations in binocular rivalry. Participants received either aversive classical conditioning of the stimuli shown alone between rivalry blocks, or aversive percept conditioning of one of the two possible perceptual choices during rivalry. Both groups showed successful aversive conditioning according to skin conductance responses and affective valence ratings. However, while classical conditioning led to an immediate but short-lived increase in dominance durations of the conditioned stimulus, percept conditioning yielded no significant immediate effect but tended to decrease durations of the conditioned percept during extinction. These results show dissociable effects of value learning on perceptual inference in situations of perceptual conflict, depending on whether learning relates to the decision between conflicting perceptual choices or the sensory stimuli per se. Copyright © 2018 Elsevier Inc. All rights reserved.

Antimicrobial Susceptibility of Enteric Gram Negative Facultative Anaerobe Bacilli in Aerobic versus Anaerobic Conditions

PubMed Central

Amachawadi, Raghavendra G.; Renter, David G.; Volkova, Victoriya V.

2016-01-01

Antimicrobial treatments result in the host’s enteric bacteria being exposed to the antimicrobials. Pharmacodynamic models can describe how this exposure affects the enteric bacteria and their antimicrobial resistance. The models utilize measurements of bacterial antimicrobial susceptibility traditionally obtained in vitro in aerobic conditions. However, in vivo enteric bacteria are exposed to antimicrobials in anaerobic conditions of the lower intestine. Some of enteric bacteria of food animals are potential foodborne pathogens, e.g., Gram-negative bacilli Escherichia coli and Salmonella enterica. These are facultative anaerobes; their physiology and growth rates change in anaerobic conditions. We hypothesized that their antimicrobial susceptibility also changes, and evaluated differences in the susceptibility in aerobic vs. anaerobic conditions of generic E. coli and Salmonella enterica of diverse serovars isolated from cattle feces. Susceptibility of an isolate was evaluated as its minimum inhibitory concentration (MIC) measured by E-Test® following 24 hours of adaptation to the conditions on Mueller-Hinton agar, and on a more complex tryptic soy agar with 5% sheep blood (BAP) media. We considered all major antimicrobial drug classes used in the U.S. to treat cattle: β-lactams (specifically, ampicillin and ceftriaxone E-Test®), aminoglycosides (gentamicin and kanamycin), fluoroquinolones (enrofloxacin), classical macrolides (erythromycin), azalides (azithromycin), sulfanomides (sulfamethoxazole/trimethoprim), and tetracyclines (tetracycline). Statistical analyses were conducted for the isolates (n≥30) interpreted as susceptible to the antimicrobials based on the clinical breakpoint interpretation for human infection. Bacterial susceptibility to every antimicrobial tested was statistically significantly different in anaerobic vs. aerobic conditions on both media, except for no difference in susceptibility to ceftriaxone on BAP agar. A satellite experiment suggested that during first days in anaerobic conditions the susceptibility changes with time. The results demonstrate that assessing effects of antimicrobial treatments on resistance in the host’s enteric bacteria that are Gram negative facultative Anaerobe Bacilli requires data on the bacterial antimicrobial susceptibility in the conditions resembling those in the intestine. PMID:27191612

Explicit spatiotemporal simulation of receptor-G protein coupling in rod cell disk membranes.

PubMed

Schöneberg, Johannes; Heck, Martin; Hofmann, Klaus Peter; Noé, Frank

2014-09-02

Dim-light vision is mediated by retinal rod cells. Rhodopsin (R), a G-protein-coupled receptor, switches to its active form (R(∗)) in response to absorbing a single photon and activates multiple copies of the G-protein transducin (G) that trigger further downstream reactions of the phototransduction cascade. The classical assumption is that R and G are uniformly distributed and freely diffusing on disk membranes. Recent experimental findings have challenged this view by showing specific R architectures, including RG precomplexes, nonuniform R density, specific R arrangements, and immobile fractions of R. Here, we derive a physical model that describes the first steps of the photoactivation cascade in spatiotemporal detail and single-molecule resolution. The model was implemented in the ReaDDy software for particle-based reaction-diffusion simulations. Detailed kinetic in vitro experiments are used to parametrize the reaction rates and diffusion constants of R and G. Particle diffusion and G activation are then studied under different conditions of R-R interaction. It is found that the classical free-diffusion model is consistent with the available kinetic data. The existence of precomplexes between inactive R and G is only consistent with the data if these precomplexes are weak, with much larger dissociation rates than suggested elsewhere. Microarchitectures of R, such as dimer racks, would effectively immobilize R but have little impact on the diffusivity of G and on the overall amplification of the cascade at the level of the G protein. Copyright © 2014 Biophysical Society. Published by Elsevier Inc. All rights reserved.

In Vitro Conservation of Date Palm Shoot-Tip Explants and Callus Cultures Under Minimal Growth Conditions.

PubMed

El-Dawayati, Maiada M

2017-01-01

Date palm fruit production has great economic significance for many countries. There is a fundamental necessity to conserve valuable date palm germplasm, but there are various problems with in vivo and ex situ conservation. In vitro storage has several advantages over conventional germplasm conservation methods. The in vitro technique offers a developed method of slow-growth storage, which is considered as an alternate solution for short- and medium-term storage of date palm germplasm under controlled conditions. Minimal growth conditions for germplasm conservation are generally achieved by reducing growth rate through modification of environmental growing conditions and culture, by using low temperatures, and the addition of growth retardants and osmotic agents. This chapter describes a protocol for short-term in vitro conservation of date palm shoot-tip and callus cultures under slow-growth storage conditions, using sucrose as an osmotic agent and abscisic acid (ABA) as a growth retardant at 15 °C for 12 months.

Complementarity and Correlations

NASA Astrophysics Data System (ADS)

Maccone, Lorenzo; Bruß, Dagmar; Macchiavello, Chiara

2015-04-01

We provide an interpretation of entanglement based on classical correlations between measurement outcomes of complementary properties: States that have correlations beyond a certain threshold are entangled. The reverse is not true, however. We also show that, surprisingly, all separable nonclassical states exhibit smaller correlations for complementary observables than some strictly classical states. We use mutual information as a measure of classical correlations, but we conjecture that the first result holds also for other measures (e.g., the Pearson correlation coefficient or the sum of conditional probabilities).

Classical conditioning through auditory stimuli in Drosophila: methods and models

PubMed Central

Menda, Gil; Bar, Haim Y.; Arthur, Ben J.; Rivlin, Patricia K.; Wyttenbach, Robert A.; Strawderman, Robert L.; Hoy, Ronald R.

2011-01-01

SUMMARY The role of sound in Drosophila melanogaster courtship, along with its perception via the antennae, is well established, as is the ability of this fly to learn in classical conditioning protocols. Here, we demonstrate that a neutral acoustic stimulus paired with a sucrose reward can be used to condition the proboscis-extension reflex, part of normal feeding behavior. This appetitive conditioning produces results comparable to those obtained with chemical stimuli in aversive conditioning protocols. We applied a logistic model with general estimating equations to predict the dynamics of learning, which successfully predicts the outcome of training and provides a quantitative estimate of the rate of learning. Use of acoustic stimuli with appetitive conditioning provides both an alternative to models most commonly used in studies of learning and memory in Drosophila and a means of testing hearing in both sexes, independently of courtship responsiveness. PMID:21832129

Cabazitaxel overcomes cisplatin resistance in germ cell tumour cells.

PubMed

Gerwing, Mirjam; Jacobsen, Christine; Dyshlovoy, Sergey; Hauschild, Jessica; Rohlfing, Tina; Oing, Christoph; Venz, Simone; Oldenburg, Jan; Oechsle, Karin; Bokemeyer, Carsten; von Amsberg, Gunhild; Honecker, Friedemann

2016-09-01

Cisplatin-based chemotherapy is highly effective in metastasized germ cell tumours (GCT). However, 10-30 % of patients develop resistance to cisplatin, requiring salvage therapy. We investigated the in vitro activity of paclitaxel and the novel taxane cabazitaxel in cisplatin-sensitive and -resistant GCT cell lines. In vitro activity of paclitaxel and cabazitaxel was determined by proliferation assays, and mode of action of cabazitaxel was assessed by western blotting and two screening approaches, i.e. whole proteome analysis and a human apoptosis array. Activity of paclitaxel and cabazitaxel was not affected by cisplatin resistance, suggesting that there is no cross-resistance between these agents in vitro. Cabazitaxel treatment showed a strong inhibitory effect on colony formation capacity. Cabazitaxel induced classical apoptosis in all cell lines, reflected by cleavage of PARP and caspase 3, without inducing specific changes in the cell cycle distribution. Using the proteomic and human apoptosis array screening approaches, differential regulation of several proteins, including members of the bcl-2 family, was found, giving first insights into the mode of action of cabazitaxel in GCT. Cabazitaxel shows promising in vitro activity in GCT cells, independent of levels of cisplatin resistance.

Prognostic and functional role of subtype-specific tumor-stroma interaction in breast cancer.

PubMed

Merlino, Giuseppe; Miodini, Patrizia; Callari, Maurizio; D'Aiuto, Francesca; Cappelletti, Vera; Daidone, Maria Grazia

2017-10-01

None of the clinically relevant gene expression signatures available for breast cancer were specifically developed to capture the influence of the microenvironment on tumor cells. Here, we attempted to build subtype-specific signatures derived from an in vitro model reproducing tumor cell modifications after interaction with activated or normal stromal cells. Gene expression signatures derived from HER2+, luminal, and basal breast cancer cell lines (treated by normal fibroblasts or cancer-associated fibroblasts conditioned media) were evaluated in clinical tumors by in silico analysis on published gene expression profiles (GEPs). Patients were classified as microenvironment-positive (μENV+ve), that is, with tumors showing molecular profiles suggesting activation by the stroma, or microenvironment-negative (μENV-ve) based on correlation of their tumors' GEP with the respective subtype-specific signature. Patients with estrogen receptor alpha (ER)+/HER2-/μENV+ve tumors were characterized by 2.5-fold higher risk of developing distant metastases (HR = 2.546; 95% CI: 1.751-3.701, P = 9.84E-07), while μENV status did not affect, or only suggested the risk of distant metastases, in women with HER2+ (HR = 1.541; 95% CI: 0.788-3.012, P = 0.206) or ER-/HER2- tumors (HR = 1.894; 95% CI: 0.938-3.824; P = 0.0747), respectively. In ER+/HER2- tumors, the μENV status remained significantly associated with metastatic progression (HR = 2.098; CI: 1.214-3.624; P = 0.00791) in multivariable analysis including size, age, and Genomic Grade Index. Validity of our in vitro model was also supported by in vitro biological endpoints such as cell growth (MTT assay) and migration/invasion (Transwell assay). In vitro-derived gene signatures tracing the bidirectional interaction with cancer activated fibroblasts are subtype-specific and add independent prognostic information to classical prognostic variables in women with ER+/HER2- tumors. © 2017 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.

Paracrine interactions between LNCaP prostate cancer cells and bioengineered bone in 3D in vitro culture reflect molecular changes during bone metastasis.

PubMed

Sieh, Shirly; Taubenberger, Anna V; Lehman, Melanie L; Clements, Judith A; Nelson, Colleen C; Hutmacher, Dietmar W

2014-06-01

As microenvironmental factors such as three-dimensionality and cell-matrix interactions are increasingly being acknowledged by cancer biologists, more complex 3D in vitro models are being developed to study tumorigenesis and cancer progression. To better understand the pathophysiology of bone metastasis, we have established and validated a 3D indirect co-culture model to investigate the paracrine interactions between prostate cancer (PCa) cells and human osteoblasts. Co-culture of the human PCa, LNCaP cells embedded within polyethylene glycol hydrogels with human osteoblasts in the form of a tissue engineered bone construct (TEB), resulted in reduced proliferation of LNCaP cells. LNCaP cells in both monoculture and co-culture were responsive to the androgen analog, R1881, as indicated by an increase in the expression (mRNA and/or protein induction) of androgen-regulated genes including prostate specific antigen and fatty acid synthase. Microarray gene expression analysis further revealed an up-regulation of bone markers and other genes associated with skeletal and vasculature development and a significant activation of transforming growth factor β1 downstream genes in LNCaP cells after co-culture with TEB. LNCaP cells co-cultured with TEB also unexpectedly showed similar changes in classical androgen-responsive genes under androgen-deprived conditions not seen in LNCaP monocultures. The molecular changes of LNCaP cells after co-culturing with TEBs suggest that osteoblasts exert a paracrine effect that may promote osteomimicry and modulate the expression of androgen-responsive genes in LNCaP cells. Taken together, we have presented a novel 3D in vitro model that allows the study of cellular and molecular changes occurring in PCa cells and osteoblasts that are relevant to metastatic colonization of bone. This unique in vitro model could also facilitate cancer biologists to dissect specific biological hypotheses via extensive genomic or proteomic assessments to further our understanding of the PCa-bone crosstalk. Crown Copyright © 2014. Published by Elsevier Inc. All rights reserved.

Both Trace and Delay Conditioning of Evaluative Responses Depend on Contingency Awareness

ERIC Educational Resources Information Center

Kattner, Florian; Ellermeier, Wolfgang; Tavakoli, Paniz

2012-01-01

Whereas previous evaluative conditioning (EC) studies produced inconsistent results concerning the role of contingency knowledge, there are classical eye-blink conditioning studies suggesting that declarative processes are involved in trace conditioning but not in delay conditioning. In two EC experiments pairing neutral sounds (conditioned…

Nebulized isotonic saline versus water following a laryngeal desiccation challenge in classically trained sopranos.

PubMed

Tanner, Kristine; Roy, Nelson; Merrill, Ray M; Muntz, Faye; Houtz, Daniel R; Sauder, Cara; Elstad, Mark; Wright-Costa, Julie

2010-12-01

To examine the effects of nebulized isotonic saline (IS) versus sterile water (SW) on self-perceived phonatory effort (PPE) and phonation threshold pressure (PTP) following a surface laryngeal dehydration challenge in classically trained sopranos. In a double-blind, within-subject crossover design, 34 sopranos breathed dry air (relative humidity < 1%) transorally for 15 min and then nebulized 3 mL of IS or SW, or experienced a no-treatment control condition over 3 consecutive weeks. PPE and PTP were measured every 15 min from baseline through 2 hr postdesiccation. PPE increased significantly following the laryngeal desiccation challenge in all 3 treatment conditions (p < .01). After nebulization, PPE returned to baseline for the IS condition only. For the SW and control conditions, PPE remained above baseline during the 2 hr after desiccation. No statistically significant changes in PTP following laryngeal desiccation were observed, although values for the IS condition remained below baseline for nearly 2 hr after nebulization. PPE and PTP were not significantly correlated. Following a laryngeal surface dehydration challenge, classically trained sopranos reported increased vocal effort that persisted for at least 2 hr. Compared with SW, nebulized IS showed promise as an effective way to remediate the adverse, self-perceived effects of laryngeal desiccation.

Responses of antioxidant enzymes, photosynthetic pigments and carbohydrates in micropropagated Pitcairnia encholirioides L.B. Sm. (Bromeliaceae) under ex vitro water deficit and after rehydration.

PubMed

Resende, C F; Pacheco, V S; Dornellas, F F; Oliveira, A M S; Freitas, J C E; Peixoto, P H P

2018-03-22

In this study, the activities of antioxidant enzymes, photosynthetic pigments, proline and carbohydrate contents in Pitcairnia encholirioides under ex vitro conditions of water deficit were evaluated. Results show that plants under progressive water stress, previously in vitro cultured in media supplemented with 30 g L-1 sucrose and GA3, accumulated more proline and increased peroxidase (POD) activity and the contents of photosynthetic pigments and carbohydrates. For plants previously in vitro cultured with 15 g L-1 sucrose and NAA, no differences were found for proline content and there were reductions in activities of peroxidase (POD), catalase (CAT) and poliphenoloxidase (PPO), and in contents of carbohydrates, with progress of ex vitro water deficit. After rehydration, plants showed physiological recovery, with enzymatic activities and contents of metabolites similar to those found in the controls not submitted to dehydration, regardless of the previous in vitro culture conditions. These results show that micropropagated P. encholirioides has high tolerance to dehydration once in ex vitro conditions, which can ensure the survival of plants from tissue culture when transferred to its natural environment, emphasizing the importance of such biotechnology for the propagation of endangered species.

An experimental model for the study of cognitive disorders: the hippocampus and associative learning in mice.

PubMed

Delgado-García, José M; Gruart, Agnès

2008-12-01

The availability of transgenic mice mimicking selective human neurodegenerative and psychiatric disorders calls for new electrophysiological and microstimulation techniques capable of being applied in vivo in this species. In this article, we will concentrate on experiments and techniques developed in our laboratory during the past few years. Thus we have developed different techniques for the study of learning and memory capabilities of wild-type and transgenic mice with deficits in cognitive functions, using classical conditioning procedures. These techniques include different trace (tone/SHOCK and shock/SHOCK) conditioning procedures ? that is, a classical conditioning task involving the cerebral cortex, including the hippocampus. We have also developed implantation and recording techniques for evoking long-term potentiation (LTP) in behaving mice and for recording the evolution of field excitatory postsynaptic potentials (fEPSP) evoked in the hippocampal CA1 area by the electrical stimulation of the commissural/Schaffer collateral pathway across conditioning sessions. Computer programs have also been developed to quantify the appearance and evolution of eyelid conditioned responses and the slope of evoked fEPSPs. According to the present results, the in vivo recording of the electrical activity of selected hippocampal sites during classical conditioning of eyelid responses appears to be a suitable experimental procedure for studying learning capabilities in genetically modified mice, and an excellent model for the study of selected neuropsychiatric disorders compromising cerebral cortex functioning.

Immobilized monolithic enzymatic reactor and its application for analysis of in-vitro fertilization media samples.

PubMed

Chen, Wei-Qiang; Obermayr, Philipp; Černigoj, Urh; Vidič, Jana; Panić-Janković, Tanta; Mitulović, Goran

2017-11-01

Classical proteomics approaches involve enzymatic hydrolysis of proteins (either separated by polyacrylamide gels or in solution) followed by peptide identification using LC-MS/MS analysis. This method requires normally more than 16 h to complete. In the case of clinical analysis, it is of the utmost importance to provide fast and reproducible analysis with minimal manual sample handling. Herein we report the method development for online protein digestion on immobilized monolithic enzymatic reactors (IMER) to accelerate protein digestion, reduce manual sample handling, and provide reproducibility to the digestion process in clinical laboratory. An integrated online digestion and separation method using monolithic immobilized enzymatic reactor was developed and applied to digestion and separation of in-vitro-fertilization media. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

[Tissue engineering with mesenchymal stem cells for cartilage and bone regeneration].

PubMed

Schaefer, D J; Klemt, C; Zhang, X H; Stark, G B

2000-09-01

Tissue engineering offers the possibility to fabricate living substitutes for tissues and organs by combining histogenic cells and biocompatible carrier materials. Pluripotent mesenchymal stem cells are isolated and subcultured ex vivo and then their histogenic differentiation is induced by external factors. The fabrication of bone and cartilage constructs, their combinations and gene therapeutic approaches are demonstrated. Advantages and disadvantages of these methods are described by in vitro and in vitro testing. The proof of histotypical function after implantation in vivo is essential. The use of autologous cells and tissue engineering methods offers the possibility to overcome the disadvantages of classical tissue reconstruction--donor site morbidity of autologous grafts, immunogenicity of allogenic grafts and loosening of alloplastic implants. Furthermore, tissue engineering widens the spectrum of surgical indications in bone and cartilage reconstruction.

Electrical stimulation of the rostral medial prefrontal cortex in rabbits inhibits the expression of conditioned eyelid responses but not their acquisition

PubMed Central

Leal-Campanario, Rocío; Fairén, Alfonso; Delgado-García, José M.; Gruart, Agnès

2007-01-01

We have studied the role of rostral medial prefrontal cortex (mPFC) on reflexively evoked blinks and on classically conditioned eyelid responses in alert-behaving rabbits. The rostral mPFC was identified by its afferent projections from the medial half of the thalamic mediodorsal nuclear complex. Classical conditioning consisted of a delay paradigm using a 370-ms tone as the conditioned stimulus (CS) and a 100-ms air puff directed at the left cornea as the unconditioned stimulus (US). The CS coterminated with the US. Electrical train stimulation of the contralateral rostral mPFC produced a significant inhibition of air-puff-evoked blinks. The same train stimulation of the rostral mPFC presented during the CS–US interval for 10 successive conditioning sessions significantly reduced the generation of conditioned responses (CRs) as compared with values reached by control animals. Interestingly, the percentage of CRs almost reached control values when train stimulation of the rostral mPFC was removed from the fifth conditioning session on. The electrical stimulation of the rostral mPFC in well conditioned animals produced a significant decrease in the percentage of CRs. Moreover, the stimulation of the rostral mPFC was also able to modify the kinematics (latency, amplitude, and velocity) of evoked CRs. These results suggest that the rostral mPFC is a potent inhibitor of reflexively evoked and classically conditioned eyeblinks but that activation prevents only the expression of CRs, not their latent acquisition. Functional and behavioral implications of this inhibitory role of the rostral mPFC are discussed. PMID:17592148

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

Hayashi, A.; Hashimoto, T.; Horibe, M.

In quantum teleportation, neither Alice nor Bob acquires any classical knowledge on teleported states. The teleportation protocol is said to be oblivious to both parties. In remote state preparation (RSP), it is assumed that Alice is given complete classical knowledge on the state that is to be prepared by Bob. Recently, Leung and Shor [e-print quant-ph/0201008] showed that the same amount of classical information as that in teleportation needs to be transmitted in any exact and deterministic RSP protocol that is oblivious to Bob. Assuming that the dimension of subsystems in the prior-entangled state is the same as the dimensionmore » of the input space, we study similar RSP protocols, but not necessarily oblivious to Bob. We show that in this case Bob's quantum operation can be safely assumed to be a unitary transformation. We then derive an equation that is a necessary and sufficient condition for such a protocol to exist. By studying this equation, we show that one-qubit RSP requires two classical bits of communication, which is the same amount as in teleportation, even if the protocol is not assumed oblivious to Bob. For higher dimensions, it is still an open question whether the amount of classical communication can be reduced by abandoning oblivious conditions.« less

An unusual presentation of eosinophilic angiocentric fibrosis.

PubMed

Hardman, Joel; Toon, Christopher; Nirmalananda, Arjuna

2017-12-01

Eosinophilic angiocentric fibrosis (EAF) is a rare, benign condition affecting the respiratory mucosa and is generally characterized by a locally destructive growth. We present a case of a lady with a saddle nose deformity that had for many years been treated as granulomatosis with polyangiitis (GPA), of which saddle nose deformity is a classic feature. At the time of surgery, she was found to have subglottic stenosis another classic feature of GPA, however, histology demonstrated EAF. We discuss the difference between the two conditions and highlight the importance of making the correct diagnosis.

Redundancy of constraints in the classical and quantum theories of gravitation.

NASA Technical Reports Server (NTRS)

Moncrief, V.

1972-01-01

It is shown that in Dirac's version of the quantum theory of gravitation, the Hamiltonian constraints are greatly redundant. If the Hamiltonian constraint condition is satisfied at one point on the underlying, closed three-dimensional manifold, then it is automatically satisfied at every point, provided only that the momentum constraints are everywhere satisfied. This permits one to replace the usual infinity of Hamiltonian constraints by a single condition which may be taken in the form of an integral over the manifold. Analogous theorems are given for the classical Einstein Hamilton-Jacobi equations.

Completed Beltrami-Michell Formulation for Analyzing Radially Symmetrical Bodies

NASA Technical Reports Server (NTRS)

Kaljevic, Igor; Saigal, Sunil; Hopkins, Dale A.; Patnaik, Surya N.

1994-01-01

A force method formulation, the completed Beltrami-Michell formulation (CBMF), has been developed for analyzing boundary value problems in elastic continua. The CBMF is obtained by augmenting the classical Beltrami-Michell formulation with novel boundary compatibility conditions. It can analyze general elastic continua with stress, displacement, or mixed boundary conditions. The CBMF alleviates the limitations of the classical formulation, which can solve stress boundary value problems only. In this report, the CBMF is specialized for plates and shells. All equations of the CBMF, including the boundary compatibility conditions, are derived from the variational formulation of the integrated force method (IFM). These equations are defined only in terms of stresses. Their solution for kinematically stable elastic continua provides stress fields without any reference to displacements. In addition, a stress function formulation for plates and shells is developed by augmenting the classical Airy's formulation with boundary compatibility conditions expressed in terms of the stress function. The versatility of the CBMF and the augmented stress function formulation is demonstrated through analytical solutions of several mixed boundary value problems. The example problems include a composite circular plate and a composite circular cylindrical shell under the simultaneous actions of mechanical and thermal loads.

Susceptibility of bone marrow-derived macrophages to influenza virus infection is dependent on macrophage phenotype.

PubMed

Campbell, Gillian M; Nicol, Marlynne Q; Dransfield, Ian; Shaw, Darren J; Nash, Anthony A; Dutia, Bernadette M

2015-10-01

The role of the macrophage in influenza virus infection is complex. Macrophages are critical for resolution of influenza virus infections but implicated in morbidity and mortality in severe infections. They can be infected with influenza virus and consequently macrophage infection is likely to have an impact on the host immune response. Macrophages display a range of functional phenotypes, from the prototypical pro-inflammatory classically activated cell to alternatively activated anti-inflammatory macrophages involved in immune regulation and wound healing. We were interested in how macrophages of different phenotype respond to influenza virus infection and therefore studied the infection of bone marrow-derived macrophages (BMDMs) of classical and alternative phenotype in vitro. Our results show that alternatively activated macrophages are more readily infected and killed by the virus than classically activated. Classically activated BMDMs express the pro-inflammatory markers inducible nitric oxide synthase (iNOS) and TNF-α, and TNF-α expression was further upregulated following infection. Alternatively activated macrophages express Arginase-1 and CD206; however, following infection, expression of these markers was downregulated whilst expression of iNOS and TNF-α was upregulated. Thus, infection can override the anti-inflammatory state of alternatively activated macrophages. Importantly, however, this results in lower levels of pro-inflammatory markers than those produced by classically activated cells. Our results showed that macrophage phenotype affects the inflammatory macrophage response following infection, and indicated that modulating the macrophage phenotype may provide a route to develop novel strategies to prevent and treat influenza virus infection.

The zinc fingers of YY1 bind single-stranded RNA with low sequence specificity.

PubMed

Wai, Dorothy C C; Shihab, Manar; Low, Jason K K; Mackay, Joel P

2016-11-02

Classical zinc fingers (ZFs) are traditionally considered to act as sequence-specific DNA-binding domains. More recently, classical ZFs have been recognised as potential RNA-binding modules, raising the intriguing possibility that classical-ZF transcription factors are involved in post-transcriptional gene regulation via direct RNA binding. To date, however, only one classical ZF-RNA complex, that involving TFIIIA, has been structurally characterised. Yin Yang-1 (YY1) is a multi-functional transcription factor involved in many regulatory processes, and binds DNA via four classical ZFs. Recent evidence suggests that YY1 also interacts with RNA, but the molecular nature of the interaction remains unknown. In the present work, we directly assess the ability of YY1 to bind RNA using in vitro assays. Systematic Evolution of Ligands by EXponential enrichment (SELEX) was used to identify preferred RNA sequences bound by the YY1 ZFs from a randomised library over multiple rounds of selection. However, a strong motif was not consistently recovered, suggesting that the RNA sequence selectivity of these domains is modest. YY1 ZF residues involved in binding to single-stranded RNA were identified by NMR spectroscopy and found to be largely distinct from the set of residues involved in DNA binding, suggesting that interactions between YY1 and ssRNA constitute a separate mode of nucleic acid binding. Our data are consistent with recent reports that YY1 can bind to RNA in a low-specificity, yet physiologically relevant manner. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

In vitro and in vivo evaluations of three computer-aided shade matching instruments.

PubMed

Yuan, Kun; Sun, Xiang; Wang, Fu; Wang, Hui; Chen, Ji-hua

2012-01-01

This study evaluated the accuracy and reliability of three computer-aided shade matching instruments (Shadepilot, VITA Easyshade, and ShadeEye NCC) using both in vitro and in vivo models. The in vitro model included the measurement of five VITA Classical shade guides. The in vivo model utilized three instruments to measure the central region of the labial surface of maxillary right central incisors of 85 people. The accuracy and reliability of the three instruments in these two evaluating models were calculated. Significant differences were observed in the accuracy of instruments both in vitro and in vivo. No significant differences were found in the reliability of instruments between and within the in vitro and the in vivo groups. VITA Easyshade was significantly different in accuracy between in vitro and in vivo models, while no significant difference was found for the other two instruments. Shadepilot was the only instrument tested in the present study that showed high accuracy and reliability both in vitro and in vivo. Significant differences were observed in the L*a*b* values of the 85 natural teeth measured using three instruments in the in vivo assessment. The pair-agreement rates of shade matching among the three instruments ranged from 37.7% to 48.2%, and the incidence of identical shade results shared by all three instruments was 25.9%. As different L*a*b* values and shade matching results were reported for the same tooth, a combination of the evaluated shade matching instruments and visual shade confirmation is recommended for clinical use.

Structure-Activity–Dependent Regulation of Cell Communication by Perfluorinated Fatty Acids using in Vivo and in Vitro Model Systems

PubMed Central

Upham, Brad L.; Park, Joon-Suk; Babica, Pavel; Sovadinova, Iva; Rummel, Alisa M.; Trosko, James E.; Hirose, Akihiko; Hasegawa, Ryuichi; Kanno, Jun; Sai, Kimie

2009-01-01

Background Perfluoroalkanoates, [e.g., perfluorooctanoate (PFOA)], are known peroxisome proliferators that induce hepatomegaly and hepatocarcinogenesis in rodents, and are classic non-genotoxic carcinogens that inhibit in vitro gap-junctional intercellular communication (GJIC). This inhibition of GJIC is known to be a function of perfluorinated carbon lengths ranging from 7 to 10. Objectives The aim of this study was to determine if the inhibition of GJIC by PFOA but not perfluoropentanoate (PFPeA) observed in F344 rat liver cells in vitro also occurs in F344 rats in vivo and to determine mechanisms of PFOA dysregulation of GJIC using in vitro assay systems. Methods We used an incision load/dye transfer technique to assess GJIC in livers of rats exposed to PFOA and PFPeA. We used in vitro assays with inhibitors of cell signaling enzymes and antioxidants known to regulate GJIC to identify which enzymes regulated PFOA-induced inhibition of GJIC. Results PFOA inhibited GJIC and induced hepatomegaly in rat livers, whereas PFPeA had no effect on either end point. Serum biochemistry of liver enzymes indicated no cytotoxic response to these compounds. In vitro analysis of mitogen-activated protein kinase (MAPK) indicated that PFOA, but not PFPeA, can activate the extracellular receptor kinase (ERK). Inhibition of GJIC, in vitro, by PFOA depended on the activation of both ERK and phosphatidylcholine-specific phospholipase C (PC-PLC) in the dysregulation of GJIC in an oxidative-dependent mechanism. Conclusions The in vitro analysis of GJIC, an epigenetic marker of tumor promoters, can also predict the in vivo activity of PFOA, which dysregulated GJIC via ERK and PC-PLC. PMID:19440492

Detection of chromosomal changes in chronic lymphocytic leukemia using classical cytogenetic methods and FISH: application of rich mitogen mixtures for lymphocyte cultures.

PubMed

Koczkodaj, Dorota; Popek, Sylwia; Zmorzyński, Szymon; Wąsik-Szczepanek, Ewa; Filip, Agata A

2016-04-01

One of the research methods of prognostic value in chronic lymphocytic leukemia (CLL) is cytogenetic analysis. This method requires the presence of appropriate B-cell mitogens in cultures in order to obtain a high mitotic index. The aim of our research was to determine the most effective methods of in vitro B-cell stimulation to maximize the number of metaphases from peripheral blood cells of patients with CLL for classical cytogenetic examination, and then to correlate the results with those obtained using fluorescence in situ hybridization (FISH). The study group involved 50 consecutive patients with CLL. Cell cultures were maintained with the basic composition of culture medium and addition of respective stimulators. We used the following stimulators: Pokeweed Mitogen (PWM), 12-O-tetradecanoylphorbol 13-acetate (TPA), ionophore, lipopolysaccharide (LPS), and CpG-oligonucleotide DSP30. We received the highest mitotic index when using the mixture of PWM+TPA+I+DSP30. With classical cytogenetic tests using banding techniques, numerical and structural aberrations of chromosomes were detected in 46 patients, and no change was found in only four patients. Test results clearly confirmed the legitimacy of using cell cultures enriched with the mixture of cell stimulators and combining classical cytogenetic techniques with the FISH technique in later patient diagnosing. Copyright © 2016 American Federation for Medical Research.

Model lipid bilayers mimic non-specific interactions of gold nanoparticles with macrophage plasma membranes.

PubMed

Montis, Costanza; Generini, Viola; Boccalini, Giulia; Bergese, Paolo; Bani, Daniele; Berti, Debora

2018-04-15

Understanding the interaction between nanomaterials and biological interfaces is a key unmet goal that still hampers clinical translation of nanomedicine. Here we investigate and compare non-specific interaction of gold nanoparticles (AuNPs) with synthetic lipid and wild type macrophage membranes. A comprehensive data set was generated by systematically varying the structural and physicochemical properties of the AuNPs (size, shape, charge, surface functionalization) and of the synthetic membranes (composition, fluidity, bending properties and surface charge), which allowed to unveil the matching conditions for the interaction of the AuNPs with macrophage plasma membranes in vitro. This effort directly proved for the first time that synthetic bilayers can be set to mimic and predict with high fidelity key aspects of nanoparticle interaction with macrophage eukaryotic plasma membranes. It then allowed to model the experimental observations according to classical interface thermodynamics and in turn determine the paramount role played by non-specific contributions, primarily electrostatic, Van der Waals and bending energy, in driving nanoparticle-plasma membrane interactions. Copyright © 2018 Elsevier Inc. All rights reserved.

Mechanisms of stress-induced cellular HSP72 release: implications for exercise-induced increases in extracellular HSP72.

PubMed

Lancaster, Graeme I; Febbraio, Mark A

2005-01-01

The heat shock proteins are a family of highly conserved proteins with critical roles in maintaining cellular homeostasis and in protecting the cell from stressful conditions. While the critical intracellular roles of heat shock proteins are undisputed, evidence suggests that the cell possess the necessary machinery to actively secrete specific heat shock proteins in response to cellular stress. In this review, we firstly discuss the evidence that physical exercise induces the release of heat shock protein 72 from specific tissues in humans. Importantly, it appears as though this release is the result of an active secretory process, as opposed to non-specific processes such as cell lysis. Next we discuss recent in vitro evidence that has identified a mechanistic basis for the observation that cellular stress induces the release of a specific subset of heat shock proteins. Importantly, while the classical protein secretory pathway does not seem to be involved in the stress-induced release of HSP72, we discuss the evidence that lipid-rafts and exosomes are important mediators of the stress-induced release of HSP72.

Fungi associated with drug recalls and rare disease outbreaks.

PubMed

Ahearn, Donald G; Doyle Stulting, R

2014-11-01

Fungi rarely cause disease outbreaks associated with use of microbe-contaminated drugs. These rare episodes typically involve a restricted spectrum of common environmental species with relatively low virulence, rather than classical pathogens. Review of data involving over-the-counter contact lens solutions and prescription drug-related recalls revealed six episodes during the past decade with significant adverse health and financial impact (including loss of vision and death). Contaminations involved fungi mostly identified with the genera Aspergillus, Exserohilum, Fusarium, Paecilomyces, and Rhizopus. These organisms are noted for their capacity to produce resistant morphotypes (chlamydoconidia, ascospores) under various adverse conditions, generally with temperature survival/tolerances markedly in excess of maximal growth temperatures. High constituent levels of melanin, trehalose and heat-shock proteins facilitate differential survival of morphotypes following exposures to toxic chemicals and temperatures above 80 °C. Adverse environmental factors that induce resistant morphotypes are suggested to occur more readily in situ than during in vitro testing. Rare unexplained, sporadic drug contamination episodes with select thermotolerant fungi may relate, in part, to resistant dormant stages.

Biological Basis for Syphilis

PubMed Central

LaFond, Rebecca E.; Lukehart, Sheila A.

2006-01-01

Syphilis is a chronic sexually transmitted disease caused by Treponema pallidum subsp. pallidum. Clinical manifestations separate the disease into stages; late stages of disease are now uncommon compared to the preantibiotic era. T. pallidum has an unusually small genome and lacks genes that encode many metabolic functions and classical virulence factors. The organism is extremely sensitive to environmental conditions and has not been continuously cultivated in vitro. Nonetheless, T. pallidum is highly infectious and survives for decades in the untreated host. Early syphilis lesions result from the host's immune response to the treponemes. Bacterial clearance and resolution of early lesions results from a delayed hypersensitivity response, although some organisms escape to cause persistent infection. One factor contributing to T. pallidum's chronicity is the paucity of integral outer membrane proteins, rendering intact organisms virtually invisible to the immune system. Antigenic variation of TprK, a putative surface-exposed protein, is likely to contribute to immune evasion. T. pallidum remains exquisitely sensitive to penicillin, but macrolide resistance has recently been identified in a number of geographic regions. The development of a syphilis vaccine, thus far elusive, would have a significant positive impact on global health. PMID:16418521

Effects of Stirring and Fluid Perfusion on the In Vitro Degradation of Calcium Phosphate Cement/PLGA Composites.

PubMed

An, Jie; Leeuwenburgh, Sander C G; Wolke, Joop G C; Jansen, John A

2015-11-01

In vitro degradation rates of calcium phosphate bioceramics are investigated using a large variation of soaking protocols that do not all match the dynamic conditions of the perfused physiological environment. Therefore, we studied the effect of stirring and fluid perfusion on the in vitro degradation rate of apatitic calcium phosphate cements (CPC) containing poly(lactic-co-glycolic acid) (PLGA) microspheres. The composites were soaked in phosphate-buffered saline up to 6 weeks under unstirred, stirred, or perfused conditions followed by analysis of mass loss, compression strength, porosity, crystal phase composition, and morphology of the cement composites. The results showed that fluid perfusion reduced the decrease in pH and corresponding degradation rates, while nonperfused soaking conditions (i.e., stirred and unstirred conditions) resulted into more extensive acidification, the rate of which increased with stirring. After 2 weeks, the formation of a secondary brushite phase was observed for cement composites soaked under nonperfused (i.e., stirred and unstirred) conditions, whereas this phase was not detected in cements soaked under perfused conditions. The degradation rate of cement composites decreased in the order unstirred>stirred>perfused, as evidenced by quantification of mass loss, compression strength, and pore morphology. To summarize, we have demonstrated that soaking conditions strongly affected the in vitro degradation process of CPCs. As a consequence, it can be concluded that the experimental design of current in vitro degradation studies does not allow for correlation to (pre-)clinical studies.

Analogy between electromagnetic potentials and wave-like dynamic variables with connections to quantum theory

NASA Astrophysics Data System (ADS)

Yang, Chen

2018-05-01

The transitions from classical theories to quantum theories have attracted many interests. This paper demonstrates the analogy between the electromagnetic potentials and wave-like dynamic variables with their connections to quantum theory for audiences at advanced undergraduate level and above. In the first part, the counterpart relations in the classical electrodynamics (e.g. gauge transform and Lorenz condition) and classical mechanics (e.g. Legendre transform and free particle condition) are presented. These relations lead to similar governing equations of the field variables and dynamic variables. The Lorenz gauge, scalar potential and vector potential manifest a one-to-one similarity to the action, Hamiltonian and momentum, respectively. In the second part, the connections between the classical pictures of electromagnetic field and particle to quantum picture are presented. By characterising the states of electromagnetic field and particle via their (corresponding) variables, their evolution pictures manifest the same algebraic structure (isomorphic). Subsequently, pictures of the electromagnetic field and particle are compared to the quantum picture and their interconnections are given. A brief summary of the obtained results are presented at the end of the paper.

Applying the method of fundamental solutions to harmonic problems with singular boundary conditions

NASA Astrophysics Data System (ADS)

Valtchev, Svilen S.; Alves, Carlos J. S.

2017-07-01

The method of fundamental solutions (MFS) is known to produce highly accurate numerical results for elliptic boundary value problems (BVP) with smooth boundary conditions, posed in analytic domains. However, due to the analyticity of the shape functions in its approximation basis, the MFS is usually disregarded when the boundary functions possess singularities. In this work we present a modification of the classical MFS which can be applied for the numerical solution of the Laplace BVP with Dirichlet boundary conditions exhibiting jump discontinuities. In particular, a set of harmonic functions with discontinuous boundary traces is added to the MFS basis. The accuracy of the proposed method is compared with the results form the classical MFS.

Kupffer Cell Metabolism and Function

PubMed Central

Nguyen-Lefebvre, Anh Thu; Horuzsko, Anatolij

2015-01-01

Kupffer cells are resident liver macrophages and play a critical role in maintaining liver functions. Under physiological conditions, they are the first innate immune cells and protect the liver from bacterial infections. Under pathological conditions, they are activated by different components and can differentiate into M1-like (classical) or M2-like (alternative) macrophages. The metabolism of classical or alternative activated Kupffer cells will determine their functions in liver damage. Special functions and metabolism of Kupffer cells suggest that they are an attractive target for therapy of liver inflammation and related diseases, including cancer and infectious diseases. Here we review the different types of Kupffer cells and their metabolism and functions in physiological and pathological conditions. PMID:26937490

Evidence of plasticity in the pontocerebellar conditioned stimulus pathway during classical conditioning of the eyeblink response in the rabbit.

PubMed

Tracy, Jo Anne; Thompson, Judith K; Krupa, David J; Thompson, Richard F

2013-10-01

Electrical stimulation thresholds required to elicit eyeblinks with either pontine or cerebellar interpositus stimulation were measured before and after classical eyeblink conditioning with paired pontine stimulation (conditioned stimulus, CS) and corneal airpuff (unconditioned stimulus, US). Pontine stimulation thresholds dropped dramatically after training and returned to baseline levels following extinction, whereas interpositus thresholds and input-output functions remained stable across training sessions. Learning rate, magnitude of threshold change, and electrode placements were correlated. Pontine projection patterns to the cerebellum were confirmed with retrograde labeling techniques. These results add to the body of literature suggesting that the pons relays CS information to the cerebellum and provide further evidence of synaptic plasticity in the cerebellar network. 2013 APA, all rights reserved

Interferogram conditioning for improved Fourier analysis and application to X-ray phase imaging by grating interferometry.

PubMed

Montaux-Lambert, Antoine; Mercère, Pascal; Primot, Jérôme

2015-11-02

An interferogram conditioning procedure, for subsequent phase retrieval by Fourier demodulation, is presented here as a fast iterative approach aiming at fulfilling the classical boundary conditions imposed by Fourier transform techniques. Interference fringe patterns with typical edge discontinuities were simulated in order to reveal the edge artifacts that classically appear in traditional Fourier analysis, and were consecutively used to demonstrate the correction efficiency of the proposed conditioning technique. Optimization of the algorithm parameters is also presented and discussed. Finally, the procedure was applied to grating-based interferometric measurements performed in the hard X-ray regime. The proposed algorithm enables nearly edge-artifact-free retrieval of the phase derivatives. A similar enhancement of the retrieved absorption and fringe visibility images is also achieved.

"Deep-media culture condition" promoted lumen formation of endothelial cells within engineered three-dimensional tissues in vitro.

PubMed

Sekiya, Sachiko; Shimizu, Tatsuya; Yamato, Masayuki; Okano, Teruo

2011-03-01

In the field of tissue engineering, the induction of microvessels into tissues is an important task because of the need to overcome diffusion limitations of oxygen and nutrients within tissues. Powerful methods to create vessels in engineered tissues are needed for creating real living tissues. In this study, we utilized three-dimensional (3D) highly cell dense tissues fabricated by cell sheet technology. The 3D tissue constructs are close to living-cell dense tissue in vivo. Additionally, creating an endothelial cell (EC) network within tissues promoted neovascularization promptly within the tissue after transplantation in vivo. Compared to the conditions in vivo, however, common in vitro cell culture conditions provide a poor environment for creating lumens within 3D tissue constructs. Therefore, for determining adequate conditions for vascularizing engineered tissue in vitro, our 3D tissue constructs were cultured under a "deep-media culture conditions." Compared to the control conditions, the morphology of ECs showed a visibly strained cytoskeleton, and the density of lumen formation within tissues increased under hydrostatic pressure conditions. Moreover, the increasing expression of vascular endothelial cadherin in the lumens suggested that the vessels were stabilized in the stimulated tissues compared with the control. These findings suggested that deep-media culture conditions improved lumen formation in engineered tissues in vitro.

Discovery of N-[4-(1H-Pyrazolo[3,4-b]pyrazin-6-yl)-phenyl]-sulfonamides as Highly Active and Selective SGK1 Inhibitors

PubMed Central

2014-01-01

From a virtual screening starting point, inhibitors of the serum and glucocorticoid regulated kinase 1 were developed through a combination of classical medicinal chemistry and library approaches. This resulted in highly active small molecules with nanomolar activity and a good overall in vitro and ADME profile. Furthermore, the compounds exhibited unusually high kinase and off-target selectivity due to their rigid structure. PMID:25589934

Discovery of N-[4-(1H-Pyrazolo[3,4-b]pyrazin-6-yl)-phenyl]-sulfonamides as Highly Active and Selective SGK1 Inhibitors.

PubMed

Halland, Nis; Schmidt, Friedemann; Weiss, Tilo; Saas, Joachim; Li, Ziyu; Czech, Jörg; Dreyer, Matthias; Hofmeister, Armin; Mertsch, Katharina; Dietz, Uwe; Strübing, Carsten; Nazare, Marc

2015-01-08

From a virtual screening starting point, inhibitors of the serum and glucocorticoid regulated kinase 1 were developed through a combination of classical medicinal chemistry and library approaches. This resulted in highly active small molecules with nanomolar activity and a good overall in vitro and ADME profile. Furthermore, the compounds exhibited unusually high kinase and off-target selectivity due to their rigid structure.

Schinus terebinthifolius Raddi extract and linoleic acid from Passiflora edulis synergistically decrease melanin synthesis in B16 cells and reconstituted epidermis.

PubMed

Jorge, A T S; Arroteia, K F; Santos, I A; Andres, E; Medina, S P H; Ferrari, C R; Lourenço, C B; Biaggio, R M T T; Moreira, P L

2012-10-01

Several treatments for skin whitening are available today, but few of them are completely adequate, especially owing to the carcinogenic potential attributed to classical drugs like hydroquinone, arbutin and kojic acid. To provide an alternative and safer technology for whitening, we developed two botanical compounds originated from Brazilian biodiversity, an extract of Schinus terebinthifolius Raddi and a linoleic acid fraction isolated from Passiflora edulis oil. The whitening effect of these compounds was assessed using biochemical assays and in vitro models including cellular assays and equivalent skin. The results showed that S. terebinthifolius Raddi extract is able to reduce the tyrosinase activity in vitro, and the combination of this extract with linoleic acid is able to decrease the level of melanin produced by B16 cells cultured with melanocyte-stimulating hormone. Furthermore, melanin was also reduced in human reconstituted epidermis (containing melanocytes) treated with the compounds. The combination of the compounds may provide a synergistic positive whitening effect rather than their isolated use. Finally, we demonstrated that the performance of these mixed compounds is comparable to classical molecules used for skin whitening, as kojic acid. This new natural mixture could be considered an alternative therapeutic agent for treating hyperpigmentation and an effective component in whitening cosmetics. © 2012 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

Time-dependent variational approach in terms of squeezed coherent states: Implication to semi-classical approximation

NASA Technical Reports Server (NTRS)

Tsue, Yasuhiko

1994-01-01

A general framework for time-dependent variational approach in terms of squeezed coherent states is constructed with the aim of describing quantal systems by means of classical mechanics including higher order quantal effects with the aid of canonicity conditions developed in the time-dependent Hartree-Fock theory. The Maslov phase occurring in a semi-classical quantization rule is investigated in this framework. In the limit of a semi-classical approximation in this approach, it is definitely shown that the Maslov phase has a geometric nature analogous to the Berry phase. It is also indicated that this squeezed coherent state approach is a possible way to go beyond the usual WKB approximation.

[Traditional and modern approaches to culture of preimplantation mammalian embryos in vitro].

PubMed

Brusentsev, E Iu; Igonina, T N; Amstislavskiĭ, S Ia

2014-01-01

This review covers the basic principles and methods of in vitro culture of preimplantation mammalian embryos. The features of in vitro development of embryos of various species of animals with allowance for the composition of nutrient media are described, with special attention paid to those species that have traditionally been consideredas laboratory (i.e., mice, rats, and hamsters). The effects of suboptimal culturing conditions of preimplantation embryos on the formation of the phenotype of individuals developed from these embryos are discussed. New approaches to optimize the conditions of the development of preimplantation mammalian embryos in vitro are analyzed.

Why trace and delay conditioning are sometimes (but not always) hippocampal dependent: A computational model

PubMed Central

Moustafa, Ahmed A.; Wufong, Ella; Servatius, Richard J.; Pang, Kevin C. H.; Gluck, Mark A.; Myers, Catherine E.

2013-01-01

A recurrent-network model provides a unified account of the hippocampal region in mediating the representation of temporal information in classical eyeblink conditioning. Much empirical research is consistent with a general conclusion that delay conditioning (in which the conditioned stimulus CS and unconditioned stimulus US overlap and co-terminate) is independent of the hippocampal system, while trace conditioning (in which the CS terminates before US onset) depends on the hippocampus. However, recent studies show that, under some circumstances, delay conditioning can be hippocampal-dependent and trace conditioning can be spared following hippocampal lesion. Here, we present an extension of our prior trial-level models of hippocampal function and stimulus representation that can explain these findings within a unified framework. Specifically, the current model includes adaptive recurrent collateral connections that aid in the representation of intra-trial temporal information. With this model, as in our prior models, we argue that the hippocampus is not specialized for conditioned response timing, but rather is a general-purpose system that learns to predict the next state of all stimuli given the current state of variables encoded by activity in recurrent collaterals. As such, the model correctly predicts that hippocampal involvement in classical conditioning should be critical not only when there is an intervening trace interval, but also when there is a long delay between CS onset and US onset. Our model simulates empirical data from many variants of classical conditioning, including delay and trace paradigms in which the length of the CS, the inter-stimulus interval, or the trace interval is varied. Finally, we discuss model limitations, future directions, and several novel empirical predictions of this temporal processing model of hippocampal function and learning. PMID:23178699

Known symptoms and diseases of a number of classical European composers during 17th and 20th century in relation with their artistic musical expressions.

PubMed

Pucarin-Cvetković, Jasna; Zuskin, Eugenija; Mustajbegović, Jadranka; Janev-Holcer, Natasa; Rudan, Pavao; Milosević, Milan

2011-12-01

Medical history and relationship to the medical conditions as well as to the music creativity and productivity of some of the classical European composers have been described. In this review article we analyzed their illnesses as well as association between physical or mental diseases and their creativity and adaptability to disease. Some classical composers suffered from organic diseases, while others complained of mental disturbances. However, in spite of their disorders, the intensity of their creativity mostly remained unchanged.

Applications of supercritical fluids to enhance the dissolution behaviors of Furosemide by generation of microparticles and solid dispersions.

PubMed

De Zordi, Nicola; Moneghini, Mariarosa; Kikic, Ireneo; Grassi, Mario; Del Rio Castillo, Antonio Esau; Solinas, Dario; Bolger, Michael B

2012-05-01

The 'classical' loop diuretic drug Furosemide has been used as a model compound to investigate the possibility of enhancing the dissolution rate of poorly water-soluble drugs using supercritical anti-solvent techniques (SASs). In the present study we report upon the in vitro bioavailability improvement of Furosemide through particle size reduction as well as formation of solid dispersions (SDs) using the hydrophilic polymer Crospovidone. Supercritical carbon dioxide was used as the processing medium for these experiments. In order to successfully design a CO(2) antisolvent process, preliminary studies of Furosemide microparticles generation were conducted using Peng Robinson's Equation of State. These preliminary studies indicated using acetone as a solvent with pressures of 100 and 200bar and a temperature of 313K would yield optimum results. These operative conditions were then adopted for the SDs. Micronization by means of SAS at 200bar resulted in a significant reduction of crystallites, particle size, as well as improved dissolution rate in comparison with untreated drug. Furosemide recrystallized by SAS at 100bar and using traditional solvent evaporation. Moreover, changes in polymorphic form were observed in the 200bar samples. The physicochemical characterization of Furosemide:crospovidone SDs (1:1 and 1:2 w/w, respectively) generated by SAS revealed the presence of the drug amorphously dispersed in the 1:2 w/w sample at 100bar still remaining stable after 6months. This sample exhibits the best in vitro dissolution performance in the simulated gastric fluid (pH 1.2), in comparison with the same SD obtained by traditional method. No interactions between drug and polymer were observed. These results, together with the presence of the selected carrier, confirm that the use of Supercritical fluids antisolvent technology is a valid mean to increase the dissolution rate of poorly soluble drugs. Theoretical in vivo-in vitro relation was predicted by means of a pharmacokinetics mathematical model. Copyright © 2012 Elsevier B.V. All rights reserved.

Classical Conditioning of Profoundly Retarded, Multiply Handicapped Children.

ERIC Educational Resources Information Center

Hogg, J.; And Others

1979-01-01

Conditioning was established for the two most developmentally advanced Ss, and the intermediate pair showed different patterns of orienting response to the conditioned stimulus but no evidence of conditioning. The fifth and most developmentally delayed child did not respond to the stimuli. Journal Availability: J. B. Lippincott Co., East…

Interpersonal Attraction Under Negative Conditions: A Problem for the Classical Conditioning Paradigm?

ERIC Educational Resources Information Center

Kenrick, Douglas T.; Johnson, Gregory A.

The influence of aversive conditions on interpersonal attraction was investigated using 60 female undergraduates as subjects. Dyads were formed and equally divided into aversive (loud-noise) and neutral (low-noise) conditions. After completing an attitude survey questionnaire subjects completed a short filler task while the experimenter…

The physiology of ex vitro pineapple (Ananas comosus L. Merr. var MD-2) as CAM or C3 is regulated by the environmental conditions.

PubMed

Aragón, C; Carvalho, L; González, J; Escalona, M; Amancio, S

2012-04-01

Many plant species grown under in vitro controlled conditions can be used as models for the study of physiological processes. Adult pineapple can display CAM physiology while in vitro it functions as a C3 plant. Ex vitro Ananas comosus has plastic morphology and physiology, both easy to modify from C3 to CAM by changing the environmental conditions. The yield of survival for a rentable propagation protocol of pineapple is closely related with the C3/CAM shift and the associated physiological characteristics. In the present work, ex vitro pineapple plants were divided in two sets and subjected to C3 and CAM-inducing environmental conditions, determined by light intensity and relative humidity, respectively, 40 μmol m(-2) s(-1)/85% and 260 μmol m(-2) s(-1)/50%. The results demonstrated that the stress imposed by the environmental conditions switched pineapple plants from C3 to CAM behavior. Comparing to CAM induced, C3-induced pineapple plants showed substandard growth parameters and morphological leaf characteristics but a better rooting process and a higher ABA production, a phenotype closer to adult plants, which are expected to produce fruits in a normal production cycle. We conclude that the upholding of these characteristics is conditioned by low light intensity plus high relative humidity, especially during the first 8 weeks of ex vitro growth. It is expected that the better understanding of pineapple acclimatization will contribute to the design of a protocol to apply as a rentable tool in the pineapple agronomic industry. © Springer-Verlag 2011

Spasticity in multiple sclerosis and role of glatiramer acetate treatment

PubMed Central

Meca-Lallana, Jose Eustasio; Hernández-Clares, Rocío; Carreón-Guarnizo, Ester

2015-01-01

Introduction Spasticity is one of the most disabling and difficult-to-treat symptoms shown by patients with multiple sclerosis, who often show a suboptimal and unsatisfactory response to classic treatment and new available nonpharmacological alternatives. Due to the progressive nature of this condition, the early management should be essential to improve long-term outcomes. Methods We performed a narrative literature review of the contribution of spasticity to the burden of multiple sclerosis and the potential role of classic disease-modifying drugs. Results Added to the underlying pathophysiology of spasticity, certain external factors and drugs such as interferon may exacerbate the existing condition, hence their awareness is crucial as part of an effective management of spasticity. Furthermore, the evidence for the effectiveness of glatiramer acetate in preventing spasticity in naïve patients and in those switching from interferon should not be ignored. Conclusions This literature review proposes the examination of spasticity and the influence of classic disease-modifying agents on the level of existing condition among the variables to be considered when deciding on therapy for multiple sclerosis in clinical practice. PMID:26445705

Necessary and sufficient optimality conditions for classical simulations of quantum communication processes

NASA Astrophysics Data System (ADS)

Montina, Alberto; Wolf, Stefan

2014-07-01

We consider the process consisting of preparation, transmission through a quantum channel, and subsequent measurement of quantum states. The communication complexity of the channel is the minimal amount of classical communication required for classically simulating it. Recently, we reduced the computation of this quantity to a convex minimization problem with linear constraints. Every solution of the constraints provides an upper bound on the communication complexity. In this paper, we derive the dual maximization problem of the original one. The feasible points of the dual constraints, which are inequalities, give lower bounds on the communication complexity, as illustrated with an example. The optimal values of the two problems turn out to be equal (zero duality gap). By this property, we provide necessary and sufficient conditions for optimality in terms of a set of equalities and inequalities. We use these conditions and two reasonable but unproven hypotheses to derive the lower bound n ×2n -1 for a noiseless quantum channel with capacity equal to n qubits. This lower bound can have interesting consequences in the context of the recent debate on the reality of the quantum state.

An insertion in the methyltransferase domain of P. falciparum trimethylguanosine synthase harbors a classical nuclear localization signal.

PubMed

Babar, Prasad H; Dey, Vishakha; Jaiswar, Praveen; Patankar, Swati

Many Plasmodium falciparum proteins do not share homology with, and are generally longer than their respective orthologs. This, to some extent, can be attributed to insertions. Here, we studied a P. falciparum RNA hypermethylase, trimethylguanosine synthase (PfTGS1) that harbors a 76 amino acid insertion in its methyltransferase domain. Bioinformatics analysis revealed that this insertion was present in TGS1 orthologs from other Plasmodium species as well. Interestingly, a classical nuclear localization signal (NLS) was predicted in the insertions of primate parasite TGS1 proteins. To check whether these predicted NLS are functional, we developed an in vivo heterologous system using S. cerevisiae. The predicted NLS when fused to dimeric GFP were able to localize the fusion protein to the nucleus in yeast indicating that it is indeed recognized by the yeast nuclear import machinery. We further showed that the PfTGS1 NLS binds to P. falciparum importin-α in vitro, confirming that the NLS is also recognized by the P. falciparum classical nuclear import machinery. Thus, in this study we report a novel function of the insertion in PfTGS1. Copyright © 2016 Elsevier B.V. All rights reserved.

2006 Gender Relations of Active-Duty Members

DTIC Science & Technology

2008-03-01

sexual harassment (e.g., behaviors that might lead to a hostile work environment, or represent quid pro quo harassment ). Hostile work environments...attempts to establish a sexual relationship), and sexual coercion (classic quid pro quo instances of specific treatment or favoritism conditioned on... sexual relationship. Sexual coercion includes classic quid pro quo , instances of specific treatment or

Effects of Quercetin Supplementation on Lipid and Protein Metabolism after Classic Boxing Training

ERIC Educational Resources Information Center

Demirci, Nevzat

2017-01-01

The metabolic fitness (MF) is a component of athletes' physical conditioning. This study aims to investigate the effects of quercetin supplementation on Turkish Junior athletes' lipid and protein metabolism relating to MF after one month classic boxing training. Totally 20 voluntary junior male athletes were separated into two equal groups as the…

Rhetoric and the Social Matrix: Reflections from the Asian Classics.

ERIC Educational Resources Information Center

Oliver, Robert T.

As humanity seeks a new social matrix which is suited to the global conditions that have ended the isolation of communities, we must learn to understand the various rhetorics of different cultures. This paper explores at length some of the richness of rhetorical theory within the classics of the East, including the "Upanishads," and in the ideas…

The Prediction of Item Parameters Based on Classical Test Theory and Latent Trait Theory

ERIC Educational Resources Information Center

Anil, Duygu

2008-01-01

In this study, the prediction power of the item characteristics based on the experts' predictions on conditions try-out practices cannot be applied was examined for item characteristics computed depending on classical test theory and two-parameters logistic model of latent trait theory. The study was carried out on 9914 randomly selected students…

Traction test of temporary dental cements.

PubMed

Román-Rodríguez, Juan-Luis; Millan-Martínez, Diego; Fons-Font, Antonio; Agustín-Panadero, Rubén; Fernández-Estevan, Lucía

2017-04-01

Classic self-curing temporary cements obstruct the translucence of provisional restorations. New dual-cure esthetic temporary cements need investigation and comparison with classic cements to ensure that they are equally retentive and provide adequate translucence. The objective is to analyze by means of traction testing in a in vitro study the retention of five temporary cements. Ten molars were prepared and ten provisional resin restorations were fabricated using CAD-CAM technology (n=10). Five temporary cements were selected: self-curing temporary cements, Dycal (D), Temp Bond (TB), Temp Bond Non Eugenol (TBNE); dual-curing esthetic cements Temp Bond Clear (TBC) and Telio CS link (TE). Each sample underwent traction testing, both with thermocycling (190 cycles at 5-55º) and without thermocycling. TE and TBC obtained the highest traction resistance values. Thermocycling reduced the resistance of all cements except TBC. The dual-cure esthetic cements tested provided optimum outcomes for bonding provisional restorations. Key words: Temporary dental cements, cements resistance.

Towards the Fundamental Quantum Limit of Linear Measurements of Classical Signals

NASA Astrophysics Data System (ADS)

Miao, Haixing; Adhikari, Rana X.; Ma, Yiqiu; Pang, Belinda; Chen, Yanbei

2017-08-01

The quantum Cramér-Rao bound (QCRB) sets a fundamental limit for the measurement of classical signals with detectors operating in the quantum regime. Using linear-response theory and the Heisenberg uncertainty relation, we derive a general condition for achieving such a fundamental limit. When applied to classical displacement measurements with a test mass, this condition leads to an explicit connection between the QCRB and the standard quantum limit that arises from a tradeoff between the measurement imprecision and quantum backaction; the QCRB can be viewed as an outcome of a quantum nondemolition measurement with the backaction evaded. Additionally, we show that the test mass is more a resource for improving measurement sensitivity than a victim of the quantum backaction, which suggests a new approach to enhancing the sensitivity of a broad class of sensors. We illustrate these points with laser interferometric gravitational-wave detectors.

Quantum no-scale regimes in string theory

NASA Astrophysics Data System (ADS)

Coudarchet, Thibaut; Fleming, Claude; Partouche, Hervé

2018-05-01

We show that in generic no-scale models in string theory, the flat, expanding cosmological evolutions found at the quantum level can be attracted to a "quantum no-scale regime", where the no-scale structure is restored asymptotically. In this regime, the quantum effective potential is dominated by the classical kinetic energies of the no-scale modulus and dilaton. We find that this natural preservation of the classical no-scale structure at the quantum level occurs when the initial conditions of the evolutions sit in a subcritical region of their space. On the contrary, supercritical initial conditions yield solutions that have no analogue at the classical level. The associated intrinsically quantum universes are sentenced to collapse and their histories last finite cosmic times. Our analysis is done at 1-loop, in perturbative heterotic string compactified on tori, with spontaneous supersymmetry breaking implemented by a stringy version of the Scherk-Schwarz mechanism.

Quantum Transmission Conditions for Diffusive Transport in Graphene with Steep Potentials

NASA Astrophysics Data System (ADS)

Barletti, Luigi; Negulescu, Claudia

2018-05-01

We present a formal derivation of a drift-diffusion model for stationary electron transport in graphene, in presence of sharp potential profiles, such as barriers and steps. Assuming the electric potential to have steep variations within a strip of vanishing width on a macroscopic scale, such strip is viewed as a quantum interface that couples the classical regions at its left and right sides. In the two classical regions, where the potential is assumed to be smooth, electron and hole transport is described in terms of semiclassical kinetic equations. The diffusive limit of the kinetic model is derived by means of a Hilbert expansion and a boundary layer analysis, and consists of drift-diffusion equations in the classical regions, coupled by quantum diffusive transmission conditions through the interface. The boundary layer analysis leads to the discussion of a four-fold Milne (half-space, half-range) transport problem.

The Low-Renin Hypertension Phenotype: Genetics and the Role of the Mineralocorticoid Receptor.

PubMed

Baudrand, Rene; Vaidya, Anand

2018-02-11

A substantial proportion of patients with hypertension have a low or suppressed renin. This phenotype of low-renin hypertension (LRH) may be the manifestation of inherited genetic syndromes, acquired somatic mutations, or environmental exposures. Activation of the mineralocorticoid receptor is a common final mechanism for the development of LRH. Classically, the individual causes of LRH have been considered to be rare diseases; however, recent advances suggest that there are milder and "non-classical" variants of many LRH-inducing conditions. In this regard, our understanding of the underlying genetics and mechanisms accounting for LRH, and therefore, potentially the pathogenesis of a large subset of essential hypertension, is evolving. This review will discuss the potential causes of LRH, with a focus on implicated genetic mechanisms, the expanding recognition of non-classical variants of conditions that induce LRH, and the role of the mineralocorticoid receptor in determining this phenotype.

Sex and the stimulus-movement effect: Differences in acquisition of autoshaped responding in cynomolgus monkeys.

PubMed

Rice, Nathaniel C; Makar, Jennifer R; Myers, Todd M

2017-03-15

The stimulus-movement effect refers to the phenomenon in which stimulus discrimination or acquisition of a response is facilitated by moving stimuli as opposed to stationary stimuli. The effect has been found in monkeys, rats, and humans, but the experiments conducted did not provide adequate female representation to investigate potential sex differences. The current experiment analyzed acquisition of stimulus touching in a progressive series of classical conditioning procedures in cynomolgus monkeys (Macaca fascicularis) as a function of sex and stimulus movement. Classical conditioning tasks arrange two or more stimuli in relation to each other with different temporal and predictive relations. Autoshaping procedures overlay operant contingencies onto a classical-conditioning stimulus arrangement. In the present case, a neutral stimulus (a small gray square displayed on a touchscreen) functioned as the conditional stimulus and a food pellet functioned as the unconditional stimulus. Although touching is not required to produce food, with repeated stimulus pairings subjects eventually touch the stimulus. Across conditions of increasing stimulus correlation and temporal contiguity, male monkeys acquired the response faster with a moving stimulus. In contrast, females acquired the response faster with a stationary stimulus. These results demonstrate that the stimulus-movement effect may be differentially affected by sex and indicate that additional experiments with females are needed to determine how sex interacts with behavioral phenomena discovered and elaborated almost exclusively using males. Published by Elsevier Inc.

Socially acquired predator avoidance: is it just classical conditioning?

PubMed

Griffin, Andrea S

2008-06-15

Associative learning theories presume the existence of a general purpose learning process, the structure of which does not mirror the demands of any particular learning problem. In contrast, learning scientists working within an Evolutionary Biology tradition believe that learning processes have been shaped by ecological demands. One potential means of exploring how ecology may have modified properties of acquisition is to use associative learning theory as a framework within which to analyse a particular learning phenomenon. Recent work has used this approach to examine whether socially transmitted predator avoidance can be conceptualised as a classical conditioning process in which a novel predator stimulus acts as a conditioned stimulus (CS) and acquires control over an avoidance response after it has become associated with alarm signals of social companions, the unconditioned stimulus (US). I review here a series of studies examining the effect of CS/US presentation timing on the likelihood of acquisition. Results suggest that socially acquired predator avoidance may be less sensitive to forward relationships than traditional classical conditioning paradigms. I make the case that socially acquired predator avoidance is an exciting novel one-trial learning paradigm that could be studied along side fear conditioning. Comparisons between social and non-social learning of danger at both the behavioural and neural level may yield a better understanding of how ecology might shape properties and mechanisms of learning.

Classical eyeblink conditioning in Parkinson's disease.

PubMed

Daum, I; Schugens, M M; Breitenstein, C; Topka, H; Spieker, S

1996-11-01

Patients with Parkinson's disease (PD) show impairments of a range of motor learning tasks, including tracking or serial reaction time task learning. Our study investigated whether such deficits would also be seen on a simple type of motor learning, classic conditioning of the eyeblink response. Medicated and unmediated patients with PD showed intact unconditioned eyeblink responses and significant learning across acquisition; the learning rates did not differ from those of healthy control subjects. The overall frequency of conditioned responses was significantly higher in the medicated patients with PD relative to control subjects, and there was also some evidence of facilitation in the unmedicated patients with PD. Conditioning of electrodermal and electrocortical responses was comparable in all groups. The findings are discussed in terms of enhanced excitability of brainstem pathways in PD and of the involvement of different neuronal circuits in different types of motor learning.

Successful treatment of eosinophilic pustular folliculitis with topical tacrolimus 0.1 percent ointment.

PubMed

Ng, Shanna Shan-Yi; Tay, Yong-Kwang

2012-02-15

Classic eosinophilic pustular folliculitis (EPF), otherwise known as Ofugi disease, is a rare condition commonly treated with topical glucocorticosteroids. If this fails, oral indomethacin is frequently the next line. Because the condition is recurrent, the use of long term steroids may cause side effects such as skin atrophy, hypertrichosis, and dyspigmentation. Topical tacrolimus is an immunosuppressant that is generally used as a steroid-sparing agent in atopic dermatitis. We report a case of classic EPF, which was recurrent over 5 years that had failed topical glucocorticosteroids but was successfully treated with topical tacrolimus 0.1 percent ointment.

Synthesis of (E)-2-Styrylchromones and Flavones by Base-Catalyzed Cyclodehydration of the Appropriate β-Diketones Using Water as Solvent.

PubMed

Pinto, Joana; Silva, Vera L M; Silva, Ana M G; Silva, Artur M S

2015-06-22

A low cost, safe, clean and environmentally benign base-catalyzed cyclodehydration of appropriate β-diketones affording (E)-2-styrylchromones and flavones in good yields is disclosed. Water was used as solvent and the reactions were heated using classical and microwave heating methods, under open and closed vessel conditions. β-Diketones having electron-donating and withdrawing substituents were used to evaluate the reaction scope. The reaction products were isolated in high purity by simple filtration and recrystallization from ethanol, when using 800 mg of the starting diketone under classical reflux heating conditions.

Classical conditioning without verbal suggestions elicits placebo analgesia and nocebo hyperalgesia

PubMed Central

Bajcar, Elżbieta A.; Adamczyk, Wacław; Kicman, Paweł; Lisińska, Natalia; Świder, Karolina; Colloca, Luana

2017-01-01

The aim of this study was to examine the relationships among classical conditioning, expectancy, and fear in placebo analgesia and nocebo hyperalgesia. A total of 42 healthy volunteers were randomly assigned to three groups: placebo, nocebo, and control. They received 96 electrical stimuli, preceded by either orange or blue lights. A hidden conditioning procedure, in which participants were not informed about the meaning of coloured lights, was performed in the placebo and nocebo groups. Light of one colour was paired with pain stimuli of moderate intensity (control stimuli), and light of the other colour was paired with either nonpainful stimuli (in the placebo group) or painful stimuli of high intensity (in the nocebo group). In the control group, both colour lights were followed by control stimuli of moderate intensity without any conditioning procedure. Participants rated pain intensity, expectancy of pain intensity, and fear. In the testing phase, when both of the coloured lights were followed by identical moderate pain stimuli, we found a significant analgesic effect in the placebo group, and a significant hyperalgesic effect in the nocebo group. Neither expectancy nor fear ratings predicted placebo analgesia or nocebo hyperalgesia. It appears that a hidden conditioning procedure, without any explicit verbal suggestions, elicits placebo and nocebo effects, however we found no evidence that these effects are predicted by either expectancy or fear. These results suggest that classical conditioning may be a distinct mechanism for placebo and nocebo effects. PMID:28750001

Timing and Cue Competition in Conditioning of the Nictitating Membrane Response of the Rabbit ("Oryctolagus Cuniculus")

ERIC Educational Resources Information Center

Kehoe, E. James; Ludvig, Elliot A.; Sutton, Richard S.

2013-01-01

Rabbits were classically conditioned using compounds of tone and light conditioned stimuli (CSs) presented with either simultaneous onsets (Experiment 1) or serial onsets (Experiment 2) in a delay conditioning paradigm. Training with the simultaneous compound reduced the likelihood of a conditioned response (CR) to the individual CSs ("mutual…

Rab11 is phosphorylated by classical and novel protein kinase C isoenzymes upon sustained phorbol ester activation.

PubMed

Pavarotti, Martín; Capmany, Anahí; Vitale, Nicolas; Colombo, María Isabel; Damiani, María Teresa

2012-02-01

Rab11 is a small GTPase that controls diverse intracellular trafficking pathways. However, the molecular machinery that regulates the participation of Rab11 in those different transport events is poorly understood. In resting cells, Rab11 localizes at the endocytic recycling compartment (ERC), whereas the different protein kinase C (PKC) isoforms display a cytosolic distribution. Sustained phorbol ester stimulation induces the translocation of the classical PKCα and PKCβII isoenzymes to the ERC enriched in Rab11, and results in transferrin recycling inhibition. In contrast, novel PKCε and atypical PKCζ isoenzymes neither redistribute to the perinucleus nor modify transferrin recycling transport after phorbol ester stimulation. Although several Rabs have been shown to be phosphorylated, there is to date no evidence indicating Rab11 as a kinase substrate. In this report, we show that Rab11 appears phosphorylated in vivo in phorbol ester-stimulated cells. A bioinformatic analysis of Rab11 allowed us to identify several high-probability Ser/Thr kinase phosphorylation sites. Our results demonstrate that classical PKC (PKCα and PKCβII but not PKCβI) directly phosphorylate Rab11 in vitro. In addition, novel PKCε and PKCη but not PKCδ isoenzymes also phosphorylate Rab11. Mass spectrometry analysis revealed that Ser 177 is the Rab11 residue to be phosphorylated in vitro by either PKCβII or PKCε. In agreement, the phosphomimetic mutant, Rab11 S177D, retains transferrin at the ERC in the absence of phorbol-12-myristate-13-acetate stimulus. This report shows for the first time that Rab11 is differentially phosphorylated by distinct PKC isoenzymes and that this post-translational modification might be a regulatory mechanism of intracellular trafficking. Copyright © 2012 Soçiété Francaise des Microscopies and Société de Biologie Cellulaire de France.

Bioaccessible peptides released by in vitro gastrointestinal digestion of fermented goat milks.

PubMed

Moreno-Montoro, Miriam; Jauregi, Paula; Navarro-Alarcón, Miguel; Olalla-Herrera, Manuel; Giménez-Martínez, Rafael; Amigo, Lourdes; Miralles, Beatriz

2018-06-01

In this study, ultrafiltered goat milks fermented with the classical starter bacteria Lactobacillus delbrueckii subsp. bulgaricus and Streptococcus salivarus subsp. thermophilus or with the classical starter plus the Lactobacillus plantarum C4 probiotic strain were analyzed using ultra-high performance liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS) and/or high performance liquid chromatography-ion trap (HPLC-IT-MS/MS). Partial overlapping of the identified sequences with regard to fermentation culture was observed. Evaluation of the cleavage specificity suggested a lower proteolytic activity of the probiotic strain. Some of the potentially identified peptides had been previously reported as angiotensin-converting enzyme (ACE) inhibitory, antioxidant, and antibacterial and might account for the in vitro activity previously reported for these fermented milks. Simulated digestion of the products was conducted in the presence of a dialysis membrane to retrieve the bioaccessible peptide fraction. Some sequences with reported physiological activity resisted digestion but were found in the non-dialyzable fraction. However, new forms released by digestion, such as the antioxidant α s1 -casein 144 YFYPQL 149 , the antihypertensive α s2 -casein 90 YQKFPQY 96 , and the antibacterial α s2 -casein 165 LKKISQ 170 , were found in the dialyzable fraction of both fermented milks. Moreover, in the fermented milk including the probiotic strain, the k-casein dipeptidyl peptidase IV inhibitor (DPP-IV) 51 INNQFLPYPY 60 as well as additional ACE inhibitory or antioxidant sequences could be identified. With the aim of anticipating further biological outcomes, quantitative structure activity relationship (QSAR) analysis was applied to the bioaccessible fragments and led to potential ACE inhibitory sequences being proposed. Graphical abstract Ultrafiltered goat milks were fermented with the classical starter bacteria (St) and with St plus the L. plantarum C4 probiotic strain. Samples were analyzed using HPLC-IT-MS/MS and UPLC-Q-TOF-MS/MS. After simulated digestion and dialysis, some of the active sequences remained and new peptides with reported beneficial activities were released.

Sulforaphane regulates phenotypic and functional switching of both induced and spontaneously differentiating human monocytes.

PubMed

Pal, Sanjima; Konkimalla, V Badireenath

2016-06-01

At the site of inflammation, switching default on polarization of monocyte differentiation into classically activated macrophages (M1 type) is one of the pathogenic outcomes in several inflammatory autoimmune diseases, such as rheumatoid arthritis and osteoarthritis. In rheumatoid and osteoarthritis, a soluble collagen known as self-antigen is considered as a biomarker and acts as an important inflammatory mediator. In the present study, we investigated the effects of sulforaphane (SFN) on phenotypic changes and functional switching during in vitro induced and spontaneous differentiation of monocytes/macrophages, whose conditions were established with THP1 induced by PMA, and human peripheral blood monocytes, respectively. SFN at non-cytotoxic concentration (10μM) blocked soluble collagen induced inflammatory responses specific to M1 macrophages, COX-2, iNOS, surface CD14, CD197 expressions and production of IL12p70, suggesting that signals induced by SFN eventually shifted macrophage polarization to a direction specific to M2 macrophages (CD36high CD197extremely low). Results obtained with the induction of inflammatory conditions specific to M1 macrophages followed by SFN treatment showed that MAPKs were involved in the M1 to M2 phenotype switching. This immune-modulatory nature of SFN provides a clear indication for its ability to alleviate chronic inflammatory diseases by targeting monocytes/macrophages. Copyright © 2016 Elsevier B.V. All rights reserved.

A novel germline inactivating mutation in the CASR gene in an Italian kindred affected by familial hypocalciuric hypercalcemia.

PubMed

Falchetti, Alberto; Gozzini, Alessia; Terranegra, Annalisa; Soldati, Laura; Vezzoli, Giuseppe; Leoncini, Gigliola; Giusti, Francesca; Franceschelli, Francesco; Masi, Laura; Tanini, Annalisa; Cavalli, Loredana; Brandi, Maria Luisa

2012-05-01

Familial hypocalciuric hypercalcemia (FHH) syndrome is a rare benign condition, inherited as an autosomal dominant trait, in which inactivating mutations of the calcium-sensing receptor (CASR) gene affects the body's ability to regulate calcium homeostasis. Its outcome is featured by increased levels of serum calcium, moderate hypophosphatemia, and inadequately normal or elevated circulating parathyroid hormone levels. Affected patients are mostly asymptomatic and do not benefit from surgical resection of their mildly enlarged parathyroids. We evaluated for hypercalcemia an Italian family that was identified via a young adult male proband referred to our center for parathyroidectomy. The patients and the family members were evaluated both biochemically and genetically as suspected FHH subjects. An in vitro functional study was performed by site-directed mutagenesis, and CASR activity was monitored by measuring intracellular calcium ([Ca(2)(+)](i)). The patient had a novel germline heterozygous CASR mutation (c.361_364GATT; p.D121del/fsX122). The mutation caused a premature stop codon at codon 122, exiting a truncated protein. The biochemical phenotype of all family members carrying the heterozygous deletion was concordant with classic FHH syndrome. Our findings confirm the role of CASR gene mutational analysis to offer a valuable addition for the recognition of FHH in hypercalcemic patients not yet characterized for a positive familial history of hypercalcemia, the only condition that identifies CASR gene mutations in hypercalcemia.

Lytic phages obscure the cost of antibiotic resistance in Escherichia coli.

PubMed

Tazzyman, Samuel J; Hall, Alex R

2015-03-17

The long-term persistence of antibiotic-resistant bacteria depends on their fitness relative to other genotypes in the absence of drugs. Outside the laboratory, viruses that parasitize bacteria (phages) are ubiquitous, but costs of antibiotic resistance are typically studied in phage-free experimental conditions. We used a mathematical model and experiments with Escherichia coli to show that lytic phages strongly affect the incidence of antibiotic resistance in drug-free conditions. Under phage parasitism, the likelihood that antibiotic-resistant genetic backgrounds spread depends on their initial frequency, mutation rate and intrinsic growth rate relative to drug-susceptible genotypes, because these parameters determine relative rates of phage-resistance evolution on different genetic backgrounds. Moreover, the average cost of antibiotic resistance in terms of intrinsic growth in the antibiotic-free experimental environment was small relative to the benefits of an increased mutation rate in the presence of phages. This is consistent with our theoretical work indicating that, under phage selection, typical costs of antibiotic resistance can be outweighed by realistic increases in mutability if drug resistance and hypermutability are genetically linked, as is frequently observed in clinical isolates. This suggests the long-term distribution of antibiotic resistance depends on the relative rates at which different lineages adapt to other types of selection, which in the case of phage parasitism is probably extremely common, as well as costs of resistance inferred by classical in vitro methods.

Lytic phages obscure the cost of antibiotic resistance in Escherichia coli

PubMed Central

Tazzyman, Samuel J; Hall, Alex R

2015-01-01

The long-term persistence of antibiotic-resistant bacteria depends on their fitness relative to other genotypes in the absence of drugs. Outside the laboratory, viruses that parasitize bacteria (phages) are ubiquitous, but costs of antibiotic resistance are typically studied in phage-free experimental conditions. We used a mathematical model and experiments with Escherichia coli to show that lytic phages strongly affect the incidence of antibiotic resistance in drug-free conditions. Under phage parasitism, the likelihood that antibiotic-resistant genetic backgrounds spread depends on their initial frequency, mutation rate and intrinsic growth rate relative to drug-susceptible genotypes, because these parameters determine relative rates of phage-resistance evolution on different genetic backgrounds. Moreover, the average cost of antibiotic resistance in terms of intrinsic growth in the antibiotic-free experimental environment was small relative to the benefits of an increased mutation rate in the presence of phages. This is consistent with our theoretical work indicating that, under phage selection, typical costs of antibiotic resistance can be outweighed by realistic increases in mutability if drug resistance and hypermutability are genetically linked, as is frequently observed in clinical isolates. This suggests the long-term distribution of antibiotic resistance depends on the relative rates at which different lineages adapt to other types of selection, which in the case of phage parasitism is probably extremely common, as well as costs of resistance inferred by classical in vitro methods. PMID:25268496

Unusual Phenotypic Features in a Patient with a Novel Splice Mutation in the GHRHR Gene

PubMed Central

Hilal, Latifa; Hajaji, Yassir; Vie-Luton, Marie-Pierre; Ajaltouni, Zeina; Benazzouz, Bouchra; Chana, Maha; Chraïbi, Adelmajid; Kadiri, Abdelkrim; Amselem, Serge; Sobrier, Marie-Laure

2008-01-01

Isolated growth hormone deficiency (IGHD) may be of genetic origin. One of the few genes involved in that condition encodes the growth hormone releasing hormone receptor (GHRHR) that, through its ligand (GHRH), plays a pivotal role in the GH synthesis and secretion by the pituitary. Our objective is to describe the phenotype of two siblings born to a consanguineous union presenting with short stature (IGHD) and Magnetic Resonance Imaging (MRI) abnormalities, and to identify the molecular basis of this condition. Our main outcome measures were clinical and endocrinological investigations, MRI of the pituitary region, study of the GHRHR gene sequence and transcripts. In both patients, the severe growth retardation (−5SD) was combined with anterior pituitary hypoplasia. In addition to these classical phenotypic features for IGHD, one of the patients had a Chiari I malformation, an arachnoid cyst, and a dysmorphic anterior pituitary. A homozygous sequence variation in the consensus donor splice site of intron 1 (IVS1 + 2T > G) of the GHRHR gene was identified in both patients. Using in vitro transcription assay, we showed that this mutation results in abnormal splicing of GHRHR transcripts. In this report, which broadens the phenotype associated with GHRHR defects, we discuss the possible role of the GHRHR in the proper development of extrapituitary structures, through a mechanism that could be direct or secondary to severe GH deficiency. PMID:18297129

Radionuclides in radiation-induced bystander effect; may it share in radionuclide therapy?

PubMed

Widel, M

2017-01-01

For many years in radiobiology and radiotherapy predominated the conviction that cellular DNA is the main target for ionizing radiation, however, the view has changed in the past 20 years. Nowadays, it is assumed that not only directed (targeted) radiation effect, but also an indirect (non-targeted) effect may contribute to the result of radiation treatment. Non-targeted effect is relatively well recognized after external beam irradiation in vitro and in vivo, and comprises such phenomena like radiation-induced bystander effect (RIBE), genomic instability, adaptive response and abscopal (out of field) effect. These stress-induced and molecular signaling mediated phenomena appear in non-targeted cells as variety responses resembling that observed in directly hit cells. Bystander effects can be both detrimental and beneficial in dependence on dose, dose-rate, cell type, genetic status and experimental condition. Less is known about radionuclide-induced non-targeted effects in radionuclide therapy, although, based on characteristics of the radionuclide radiation, on experiments in vitro utilizing classical and 3-D cell cultures, and preclinical study on animals it seems obvious that exposure to radionuclide is accompanied by various bystander effects, mostly damaging, less often protective. This review summarizes existing data on radionuclide induced bystander effects comprising radionuclides emitting beta- and alpha-particles and Auger electrons used in tumor radiotherapy and diagnostics. So far, separation of the direct effect of radionuclide decay from crossfire and bystander effects in clinical targeted radionuclide therapy is impossible because of the lack of methods to assess whether, and to what extent bystander effect is involved in human organism. Considerations on this topic are also included.

N-methyl-D-aspartate receptor antagonist MK-801 impairs learning but not memory fixation or expression of classical fear conditioning in goldfish (Carassius auratus).

PubMed

Xu, X; Davis, R E

1992-04-01

The amnestic effects of the noncompetitive antagonist MK-801 on visually mediated, classic fear conditioning in goldfish (Carassius auratus) was examined in 5 experiments. MK-801 was administered 30 min before the training session on Day 1 to look for anterograde amnestic effects, immediately after training to look for retrograde amnestic effects, and before the training or test session, or both, to look for state-dependence effects. The results showed that MK-801 produced anterograde amnesia at doses that did not produce retrograde amnesia or state dependency and did not impair the expression of conditioned or unconditioned branchial suppression responses (BSRs) to the conditioned stimulus. The results indicate that MK-801 disrupts the mechanism of learning of the conditioned stimulus-unconditioned stimulus relation. Evidence is also presented that the learning processes that are disrupted by MK-801 occur during the initial stage of BSR conditioning.

Roles of Aminergic Neurons in Formation and Recall of Associative Memory in Crickets

PubMed Central

Mizunami, Makoto; Matsumoto, Yukihisa

2010-01-01

We review recent progress in the study of roles of octopaminergic (OA-ergic) and dopaminergic (DA-ergic) signaling in insect classical conditioning, focusing on our studies on crickets. Studies on olfactory learning in honey bees and fruit-flies have suggested that OA-ergic and DA-ergic neurons convey reinforcing signals of appetitive unconditioned stimulus (US) and aversive US, respectively. Our work suggested that this is applicable to olfactory, visual pattern, and color learning in crickets, indicating that this feature is ubiquitous in learning of various sensory stimuli. We also showed that aversive memory decayed much faster than did appetitive memory, and we proposed that this feature is common in insects and humans. Our study also suggested that activation of OA- or DA-ergic neurons is needed for appetitive or aversive memory recall, respectively. To account for this finding, we proposed a model in which it is assumed that two types of synaptic connections are strengthened by conditioning and are activated during memory recall, one type being connections from neurons representing conditioned stimulus (CS) to neurons inducing conditioned response and the other being connections from neurons representing CS to OA- or DA-ergic neurons representing appetitive or aversive US, respectively. The former is called stimulus–response (S–R) connection and the latter is called stimulus–stimulus (S–S) connection by theorists studying classical conditioning in vertebrates. Results of our studies using a second-order conditioning procedure supported our model. We propose that insect classical conditioning involves the formation of S–S connection and its activation for memory recall, which are often called cognitive processes. PMID:21119781

Visual discrimination transfer and modulation by biogenic amines in honeybees.

PubMed

Vieira, Amanda Rodrigues; Salles, Nayara; Borges, Marco; Mota, Theo

2018-05-10

For more than a century, visual learning and memory have been studied in the honeybee Apis mellifera using operant appetitive conditioning. Although honeybees show impressive visual learning capacities in this well-established protocol, operant training of free-flying animals cannot be combined with invasive protocols for studying the neurobiological basis of visual learning. In view of this, different attempts have been made to develop new classical conditioning protocols for studying visual learning in harnessed honeybees, though learning performance remains considerably poorer than that for free-flying animals. Here, we investigated the ability of honeybees to use visual information acquired during classical conditioning in a new operant context. We performed differential visual conditioning of the proboscis extension reflex (PER) followed by visual orientation tests in a Y-maze. Classical conditioning and Y-maze retention tests were performed using the same pair of perceptually isoluminant chromatic stimuli, to avoid the influence of phototaxis during free-flying orientation. Visual discrimination transfer was clearly observed, with pre-trained honeybees significantly orienting their flights towards the former positive conditioned stimulus (CS+), thus showing that visual memories acquired by honeybees are resistant to context changes between conditioning and the retention test. We combined this visual discrimination approach with selective pharmacological injections to evaluate the effect of dopamine and octopamine in appetitive visual learning. Both octopaminergic and dopaminergic antagonists impaired visual discrimination performance, suggesting that both these biogenic amines modulate appetitive visual learning in honeybees. Our study brings new insight into cognitive and neurobiological mechanisms underlying visual learning in honeybees. © 2018. Published by The Company of Biologists Ltd.

DNA Length Modulates the Affinity of Fragments of Genomic DNA for the Nuclear Matrix In Vitro.

PubMed

García-Vilchis, David; Aranda-Anzaldo, Armando

2017-12-01

Classical observations have shown that during the interphase the chromosomal DNA of metazoans is organized in supercoiled loops attached to a compartment known as the nuclear matrix (NM). Fragments of chromosomal DNA able to bind the isolated NM in vitro are known as matrix associated/attachment/addressed regions or MARs. No specific consensus sequence or motif has been found that may constitute a universal, defining feature of MARs. On the other hand, high-salt resistant DNA-NM interactions in situ define true DNA loop anchorage regions or LARs, that might correspond to a subset of the potential MARs but are not necessarily identical to MARs characterized in vitro, since there are several examples of MARs able to bind the NM in vitro but which are not actually bound to the NM in situ. In the present work we assayed the capacity of two LARs, as well as of shorter fragments within such LARs, for binding to the NM in vitro. Paradoxically the isolated (≈2 kb) LARs cannot bind to the NM in vitro while their shorter (≈300 pb) sub-fragments and other non-related but equally short DNA fragments, bind to the NM in a high-salt resistant fashion. Our results suggest that the ability of a given DNA fragment for binding to the NM in vitro primarily depends on the length of the fragment, suggesting that binding to the NM is modulated by the local topology of the DNA fragment in suspension that it is known to depend on the DNA length. J. Cell. Biochem. 118: 4487-4497, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Identifying Safer Anti-Wear Triaryl Phosphate Additives for Jet Engine Lubricants

PubMed Central

Baker, Paul E.; Cole, Toby B.; Cartwright, Megan; Suzuki, Stephanie M.; Thummel, Kenneth E.; Lin, Yvonne S.; Co, Aila L.; Rettie, Allan E.; Kim, Jerry H.; Furlong, Clement E.

2013-01-01

Individuals aboard jet aircraft may be exposed to potentially toxic triaryl organophosphate anti-wear lubricant additives (TAPs) that are converted by cytochromes P450 into toxic metabolites. Consequences of exposure could be reduced by using less toxic TAPs. Our goal was to determine whether an in vitro assay for inhibition of butyrylcholinesterase (BChE) by bioactivated TAPs would be predictive of inhibition of serine active-site enzymes in vivo. The in vitro assay involved TAP bioactivation with liver microsomes and NADPH, followed by incubation with human BChE and measurement of BChE activity. Of 19 TAPs tested, tert-butylated isomers produced the least BChE inhibition. To determine the relevance of these results in vivo, mice were exposed to Durad 125 (D125; a commercial mixture of TAP esters) or to TAPs demonstrating low or no BChE inhibition when assayed in vitro. Inhibition of BChE by bioactivated TAPs in vitro correlated well with inhibition of other serine active-site enzymes in vivo, with the exception of brain acetylcholinesterase and neuropathy target esterase (NTE), which were not inhibited by any TAP tested following single exposures. A recombinant catalytic domain of NTE (rNEST) exhibited classical kinetic properties of NTE. The metabolite of tri-(o-cresyl) phosphate (ToCP), 2-(o-cresyl)-4H-1,3,2-benzodioxaphosphoran-2-one (CBDP), inhibited rNEST in vitro, but with an IC50 value almost 6-times higher than for inhibition of BChE. Physiologically-relevant concentrations of the flavonoid, naringenin, dramatically reduced D125 bioconversion in vitro. The in vitro assay should provide a valuable tool for prescreening candidate TAP anti-wear additives, identifying safer additives and reducing the number of animals required for in vivo toxicity testing. PMID:23085349

Identifying safer anti-wear triaryl phosphate additives for jet engine lubricants.

PubMed

Baker, Paul E; Cole, Toby B; Cartwright, Megan; Suzuki, Stephanie M; Thummel, Kenneth E; Lin, Yvonne S; Co, Aila L; Rettie, Allan E; Kim, Jerry H; Furlong, Clement E

2013-03-25

Individuals aboard jet aircraft may be exposed to potentially toxic triaryl organophosphate anti-wear lubricant additives (TAPs) that are converted by cytochromes P450 into toxic metabolites. Consequences of exposure could be reduced by using less toxic TAPs. Our goal was to determine whether an in vitro assay for inhibition of butyrylcholinesterase (BChE) by bioactivated TAPs would be predictive of inhibition of serine active-site enzymes in vivo. The in vitro assay involved TAP bioactivation with liver microsomes and NADPH, followed by incubation with human BChE and measurement of BChE activity. Of 19 TAPs tested, tert-butylated isomers produced the least BChE inhibition. To determine the relevance of these results in vivo, mice were exposed to Durad 125 (D125; a commercial mixture of TAP esters) or to TAPs demonstrating low or no BChE inhibition when assayed in vitro. Inhibition of BChE by bioactivated TAPs in vitro correlated well with inhibition of other serine active-site enzymes in vivo, with the exception of brain acetylcholinesterase and neuropathy target esterase (NTE), which were not inhibited by any TAP tested following single exposures. A recombinant catalytic domain of NTE (rNEST) exhibited classical kinetic properties of NTE. The metabolite of tri-(o-cresyl) phosphate (ToCP), 2-(o-cresyl)-4H-1,3,2-benzodioxaphosphoran-2-one (CBDP), inhibited rNEST in vitro, but with an IC(50) value almost 6-times higher than for inhibition of BChE. Physiologically-relevant concentrations of the flavonoid naringenin dramatically reduced D125 bioconversion in vitro. The in vitro assay should provide a valuable tool for prescreening candidate TAP anti-wear additives, identifying safer additives and reducing the number of animals required for in vivo toxicity testing. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

The modification of generalized uncertainty principle applied in the detection technique of femtosecond laser

NASA Astrophysics Data System (ADS)

Li, Ziyi

2017-12-01

Generalized uncertainty principle (GUP), also known as the generalized uncertainty relationship, is the modified form of the classical Heisenberg’s Uncertainty Principle in special cases. When we apply quantum gravity theories such as the string theory, the theoretical results suggested that there should be a “minimum length of observation”, which is about the size of the Planck-scale (10-35m). Taking into account the basic scale of existence, we need to fix a new common form of Heisenberg’s uncertainty principle in the thermodynamic system and make effective corrections to statistical physical questions concerning about the quantum density of states. Especially for the condition at high temperature and high energy levels, generalized uncertainty calculations have a disruptive impact on classical statistical physical theories but the present theory of Femtosecond laser is still established on the classical Heisenberg’s Uncertainty Principle. In order to improve the detective accuracy and temporal resolution of the Femtosecond laser, we applied the modified form of generalized uncertainty principle to the wavelength, energy and pulse time of Femtosecond laser in our work. And we designed three typical systems from micro to macro size to estimate the feasibility of our theoretical model and method, respectively in the chemical solution condition, crystal lattice condition and nuclear fission reactor condition.

Comparison of three different techniques for camera and motion control of a teleoperated robot.

PubMed

Doisy, Guillaume; Ronen, Adi; Edan, Yael

2017-01-01

This research aims to evaluate new methods for robot motion control and camera orientation control through the operator's head orientation in robot teleoperation tasks. Specifically, the use of head-tracking in a non-invasive way, without immersive virtual reality devices was combined and compared with classical control modes for robot movements and camera control. Three control conditions were tested: 1) a condition with classical joystick control of both the movements of the robot and the robot camera, 2) a condition where the robot movements were controlled by a joystick and the robot camera was controlled by the user head orientation, and 3) a condition where the movements of the robot were controlled by hand gestures and the robot camera was controlled by the user head orientation. Performance, workload metrics and their evolution as the participants gained experience with the system were evaluated in a series of experiments: for each participant, the metrics were recorded during four successive similar trials. Results shows that the concept of robot camera control by user head orientation has the potential of improving the intuitiveness of robot teleoperation interfaces, specifically for novice users. However, more development is needed to reach a margin of progression comparable to a classical joystick interface. Copyright © 2016 Elsevier Ltd. All rights reserved.

In the Blink of an Eye: Investigating the Role of Awareness in Fear Responding by Measuring the Latency of Startle Potentiation

PubMed Central

Åsli, Ole; Flaten, Magne A.

2012-01-01

The latency of startle reflex potentiation may shed light on the aware and unaware processes underlying associative learning, especially associative fear learning. We review research suggesting that single-cue delay classical conditioning is independent of awareness of the contingency between the conditioned stimulus (CS) and the unconditioned stimulus (US). Moreover, we discuss research that argues that conditioning independent of awareness has not been proven. Subsequently, three studies from our lab are presented that have investigated the role of awareness in classical conditioning, by measuring the minimum latency from CS onset to observed changes in reflexive behavior. In sum, research using this method shows that startle is potentiated 30 to 100 ms after CS onset following delay conditioning. Following trace fear conditioning, startle is potentiated 1500 ms after CS presentation. These results indicate that the process underlying delay conditioned responding is independent of awareness, and that trace fear conditioned responding is dependent on awareness. Finally, this method of investigating the role of awareness is discussed and future research possibilities are proposed. PMID:24962686

Classic conditioning of the ventilatory responses in rats.

PubMed

Nsegbe, E; Vardon, G; Perruchet, P; Gallego, J

1997-10-01

Recent authors have stressed the role of conditioning in the control of breathing, but experimental evidence of this role is still sparse and contradictory. To establish that classic conditioning of the ventilatory responses can occur in rats, we performed a controlled experiment in which a 1-min tone [conditioned stimulus (CS)] was paired with a hypercapnic stimulus [8.5% CO2, unconditioned stimulus (US)]. The experimental group (n = 9) received five paired CS-US presentations, followed by one CS alone to test conditioning. This sequence was repeated six times. The control group (n = 7) received the same number of CS and US, but each US was delivered 3 min after the CS. We observed that after the CS alone, breath duration was significantly longer in the experimental than in the control group and mean ventilation was significantly lower, thus showing inhibitory conditioning. This conditioning may have resulted from the association between the CS and the inhibitory and aversive effects of CO2. The present results confirmed the high sensitivity of the respiratory controller to conditioning processes.

A Classic Near-Infrared Probe Indocyanine Green for Detecting Singlet Oxygen.

PubMed

Tang, Cheng-Yi; Wu, Feng-Yao; Yang, Min-Kai; Guo, Yu-Min; Lu, Gui-Hua; Yang, Yong-Hua

2016-02-06

The revelation of mechanisms of photodynamic therapy (PDT) at the cellular level as well as singlet oxygen (¹O₂) as a second messengers requires the quantification of intracellular ¹O₂. To detect singlet oxygen, directly measuring the phosphorescence emitted from ¹O₂ at 1270 nm is simple but limited for the low quantum yield and intrinsic efficiency of ¹O₂ emission. Another method is chemically trapping ¹O₂ and measuring fluorescence, absorption and Electron Spin Resonance (ESR). In this paper, we used indocyanine green (ICG), the only near-infrared (NIR) probe approved by the Food and Drug Administration (FDA), to detect ¹O₂ in vitro. Once it reacts with ¹O₂, ICG is decomposed and its UV absorption at 780 nm decreases with the laser irradiation. Our data demonstrated that ICG could be more sensitive and accurate than Singlet Oxygen Sensor Green reagent(®) (SOSG, a commercialized fluorescence probe) in vitro, moreover, ICG functioned with Eosin Y while SOSG failed. Thus, ICG would reasonably provide the possibility to sense ¹O₂ in vitro, with high sensitivity, selectivity and suitability to most photosensitizers.

In Vitro Generation of Vascular Wall-Resident Multipotent Stem Cells of Mesenchymal Nature from Murine Induced Pluripotent Stem Cells.

PubMed

Steens, Jennifer; Zuk, Melanie; Benchellal, Mohamed; Bornemann, Lea; Teichweyde, Nadine; Hess, Julia; Unger, Kristian; Görgens, André; Klump, Hannes; Klein, Diana

2017-04-11

The vascular wall (VW) serves as a niche for mesenchymal stem cells (MSCs). In general, tissue-specific stem cells differentiate mainly to the tissue type from which they derive, indicating that there is a certain code or priming within the cells as determined by the tissue of origin. Here we report the in vitro generation of VW-typical MSCs from induced pluripotent stem cells (iPSCs), based on a VW-MSC-specific gene code. Using a lentiviral vector expressing the so-called Yamanaka factors, we reprogrammed tail dermal fibroblasts from transgenic mice containing the GFP gene integrated into the Nestin-locus (NEST-iPSCs) to facilitate lineage tracing after subsequent MSC differentiation. A lentiviral vector expressing a small set of recently identified human VW-MSC-specific HOX genes then induced MSC differentiation. This direct programming approach successfully mediated the generation of VW-typical MSCs with classical MSC characteristics, both in vitro and in vivo. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

In Vivo and In Vitro Genotoxic and Epigenetic Effects of Two Types of Cola Beverages and Caffeine: A Multiassay Approach.

PubMed

Mateo-Fernández, Marcos; Merinas-Amo, Tania; Moreno-Millán, Miguel; Alonso-Moraga, Ángeles; Demyda-Peyrás, Sebastián

2016-01-01

The aim of this work was to assess the biological and food safety of two different beverages: Classic Coca Cola™ (CCC) and Caffeine-Free Coca Cola (CFCC). To this end, we determined the genotoxicological and biological effects of different doses of lyophilised CCC and CFCC and Caffeine (CAF), the main distinctive constituent. Their toxic/antitoxic, genotoxic/antigenotoxic, and chronic toxicity (lifespan assay) effects were determined in vivo using the Drosophila model. Their cytotoxic activities were determined using the HL-60 in vitro cancer model. In addition, clastogenic DNA toxicity was measured using internucleosomal fragmentation and SCGE assays. Their epigenetic effects were assessed on the HL-60 methylation status using some repetitive elements. The experimental results showed a slight chemopreventive effect of the two cola beverages against HL-60 leukaemia cells, probably mediated by nonapoptotic mechanisms. Finally, CCC and CAF induced a global genome hypomethylation evaluated in LINE-1 and Alu M1 repetitive elements. Overall, we demonstrated for the first time the safety of this famous beverage in in vivo and in vitro models.

In Vivo and In Vitro Genotoxic and Epigenetic Effects of Two Types of Cola Beverages and Caffeine: A Multiassay Approach

PubMed Central

Merinas-Amo, Tania; Moreno-Millán, Miguel; Alonso-Moraga, Ángeles; Demyda-Peyrás, Sebastián

2016-01-01

The aim of this work was to assess the biological and food safety of two different beverages: Classic Coca Cola™ (CCC) and Caffeine-Free Coca Cola (CFCC). To this end, we determined the genotoxicological and biological effects of different doses of lyophilised CCC and CFCC and Caffeine (CAF), the main distinctive constituent. Their toxic/antitoxic, genotoxic/antigenotoxic, and chronic toxicity (lifespan assay) effects were determined in vivo using the Drosophila model. Their cytotoxic activities were determined using the HL-60 in vitro cancer model. In addition, clastogenic DNA toxicity was measured using internucleosomal fragmentation and SCGE assays. Their epigenetic effects were assessed on the HL-60 methylation status using some repetitive elements. The experimental results showed a slight chemopreventive effect of the two cola beverages against HL-60 leukaemia cells, probably mediated by nonapoptotic mechanisms. Finally, CCC and CAF induced a global genome hypomethylation evaluated in LINE-1 and Alu M1 repetitive elements. Overall, we demonstrated for the first time the safety of this famous beverage in in vivo and in vitro models. PMID:27471731

Effects of trypsinization and of a combined trypsin, collagenase, and DNase digestion on liberation and in vitro function of satellite cells isolated from juvenile porcine muscles.

PubMed

Miersch, Claudia; Stange, Katja; Röntgen, Monika

2018-06-01

Muscle stem cells, termed satellite cells (SC), and SC-derived myogenic progenitor cells (MPC) are involved in postnatal muscle growth, regeneration, and muscle adaptability. They can be released from their natural environment by mechanical disruption and tissue digestion. The literature contains several isolation protocols for porcine SC/MPC including various digestion procedures, but comparative studies are missing. In this report, classic trypsinization and a more complex trypsin, collagenase, and DNase (TCD) digestion were performed with skeletal muscle tissue from 4- to 5-d-old piglets. The two digestion procedures were compared regarding cell yield, viability, myogenic purity, and in vitro cell function. The TCD digestion tended to result in higher cell yields than digestion with solely trypsin (statistical trend p = 0.096), whereas cell size and viability did not differ. Isolated myogenic cells from both digestion procedures showed comparable proliferation rates, expressed the myogenic marker Desmin, and initiated myogenic differentiation in vitro at similar levels. Thus, TCD digestion tended to liberate slightly more cells without changes in the tested in vitro properties of the isolated cells. Both procedures are adequate for the isolation of SC/MPC from juvenile porcine muscles but the developmental state of the animal should always be considered.

Cosmopolitan sociology and the classical canon: Ferdinand Tönnies and the emergence of global Gesellschaft.

PubMed

Inglis, David

2009-12-01

How relevant are figures from the classical sociological canon for present day efforts to found cosmopolitan forms of sociological thought? According to the critique of Ulrich Beck, the classical sociologists remain far too wedded to nation-state-centred ways of thinking to play an important role in the development of cosmopolitan sociology. This paper argues that such a critique fails to account for the ways in which certain classical sociologists were attuned to the emerging cosmopolitical conditions of their own time, were not wholly wedded to nation-state-based conceptualizations, and thus can function as both groundings of, and inspirations for, cosmopolitan sociological endeavours. The apparently unpromising case of Tönnies is focused on, the paper showing how he outlined an account of how and why a planet-spanning condition of Gesellschaft developed a position which diverges from and counterpoints Marx's analysis of similar phenomena in important ways. The stereotype of Tönnies as an arch-conservative is also dissolved, allowing him to be considered as one of the most important antecedents of contemporary cosmopolitan sociological practice and a canonical figure still relevant for present-day purposes.

Frequency of EBV associated classical Hodgkin lymphoma decreases over a 54-year period in a Brazilian population.

PubMed

Campos, Antonio Hugo Jose Froes Marques; Moreira, Adriana; Ribeiro, Karina Braga; Paes, Roberto Pinto; Zerbini, Maria Claudia; Aldred, Vera; de Souza, Carmino Antonio; Neto, Cristovam Scapulatempo; Soares, Fernando Augusto; Vassallo, Jose

2018-01-30

The epidemiology of classical Hodgkin lymphoma varies significantly in populations with different socioeconomic conditions. Among other changes, improvement in such conditions leads to a reduction in the association with EBV infection and predominance of the nodular sclerosis subtype. This study provides an overview of the epidemiology of 817 cases of classical Hodgkin lymphoma diagnosed in five reference hospitals of the State of Sao Paulo, Brazil, over 54 years (1954-2008). The cases were distributed in 3 periods (1954-1979; 1980-1999; and 2000-2008). EBV-positive cases decreased from 87% to 46%. In children and adolescents (<15 years) and in young adults (15-45 years), EBV-positive cases decreased respectively from 96% to 64%, and from 85% to 32%. The percentage of male patients declined from 80% to 58%. In older patients (>45 years), the decrease in EBV infection was not significant. Nodular Sclerosis was the most common subtype in all periods. These results support the hypothesis that, in the Brazilian State of Sao Paulo, classical Hodgkin lymphoma has changed and now shows characteristics consistent with Pattern III observed in populations that experienced a similar socioeconomic transition.

In vitro study of LDL transport under pressurized (convective) conditions.

PubMed

Cancel, Limary M; Fitting, Andrew; Tarbell, John M

2007-07-01

It is difficult to assess the transport pathways that carry low-density lipoprotein (LDL) into the artery wall in vivo, and there has been no previous in vitro study that has examined transendothelial transport under physiologically relevant pressurized (convective) conditions. Therefore, we measured water, albumin, and LDL fluxes across bovine aortic endothelial cell (BAEC) monolayers in vitro and determined the relative contributions of vesicles, paracellular transport through "breaks" in the tight junction, and "leaky" junctions associated with dying or dividing cells. Our results show that leaky junctions are the dominant pathway for LDL transport (>90%) under convective conditions and that albumin also has a significant component of transport through leaky junctions (44%). Transcellular transport of LDL by receptor-mediated processes makes a minor contribution (<10%) to overall transport under convective conditions.

Prelude to corneal tissue engineering – Gaining control of collagen organization

PubMed Central

Ruberti, Jeffrey W.; Zieske, James D.

2012-01-01

By most standard engineering practice principles, it is premature to credibly discuss the “engineering” of a human cornea. A professional design engineer would assert that we still do not know what a cornea is (and correctly so), therefore we cannot possibly build one. The proof resides in the fact that there are no clinically viable corneas based on classical tissue engineering methods available. This is possibly because tissue engineering in the classical sense (seeding a degradable scaffolding with a population synthetically active cells) does not produce conditions which support the generation of organized tissue. Alternative approaches to the problem are in their infancy and include the methods which attempt to recapitulate development or to produce corneal stromal analogs de novo which require minimal remodeling. Nonetheless, tissue engineering efforts, which have been focused on producing the fundamental functional component of a cornea (organized alternating arrays of collagen or “lamellae”) may have already provided valuable new insights and tools relevant to development, growth, remodeling and pathologies associated with connective tissue in general. This is because engineers ask a fundamentally different question (How can that be done?) than do biological scientists (How is that done?). The difference in inquiry has prompted us to closely examine (and to mimic) development as well as investigate collagen physicochemical behavior so that we may exert control over organization both in cell-culture (in vitro) and on the benchtop (de novo). Our initial results indicate that reproducing corneal stroma-like local and long-range organization of collagen may be simpler than we anticipated while controlling spacing and fibril morphology remains difficult, but perhaps not impossible in the (reasonably) near term. PMID:18775789

8-Dehydrosterols induce membrane traffic and autophagy defects through V-ATPase dysfunction in Saccharomyces cerevisae.

PubMed

Hernández, Agustín; Serrano-Bueno, Gloria; Perez-Castiñeira, José Román; Serrano, Aurelio

2015-11-01

8-Dehydrosterols are present in a wide range of biologically relevant situations, from human rare diseases to amine fungicide-treated fungi and crops. However, the molecular bases of their toxicity are still obscure. We show here that 8-dehydrosterols, but not other sterols, affect yeast vacuole acidification through V-ATPases. Moreover, erg2Δ cells display reductions in proton pumping rates consistent with ion-transport uncoupling in vitro. Concomitantly, subunit Vph1p shows conformational changes in the presence of 8-dehydrosterols. Expression of a plant vacuolar H(+)-pumping pyrophosphatase as an alternative H(+)-pump relieves Vma(-)-like phenotypes in erg2Δ-derived mutant cells. As a consequence of these acidification defects, endo- and exo-cytic traffic deficiencies that can be alleviated with a H(+)-pumping pyrophosphatase are also observed. Despite their effect on membrane traffic, 8-dehydrosterols do not induce endoplasmic reticulum stress or assembly defects on the V-ATPase. Autophagy is a V-ATPase dependent process and erg2Δ mutants accumulate autophagic bodies under nitrogen starvation similar to Vma(-) mutants. In contrast to classical Atg(-) mutants, this defect is not accompanied by impairment of traffic through the CVT pathway, processing of Pho8Δ60p, GFP-Atg8p localisation or difficulties to survive under nitrogen starvation conditions, but it is concomitant to reduced vacuolar protease activity. All in all, erg2Δ cells are autophagy mutants albeit some of their phenotypic features differ from classical Atg(-) defective cells. These results may pave the way to understand the aetiology of sterol-related diseases, the cytotoxic effect of amine fungicides, and may explain the tolerance to these compounds observed in plants. Copyright © 2015 Elsevier B.V. All rights reserved.

Use of bovine recombinant prion protein and real-time quaking-induced conversion to detect cattle transmissible mink encephalopathy prions and discriminate classical and atypical L- and H-Type bovine spongiform encephalopathy.

PubMed

Hwang, Soyoun; Greenlee, Justin J; Nicholson, Eric M

2017-01-01

Prions are amyloid-forming proteins that cause transmissible spongiform encephalopathies through a process involving conversion from the normal cellular prion protein to the pathogenic misfolded conformation (PrPSc). This conversion has been used for in vitro assays including serial protein misfolding amplification and real-time quaking induced conversion (RT-QuIC). RT-QuIC can be used for the detection of prions in a variety of biological tissues from humans and animals. Extensive work has been done to demonstrate that RT-QuIC is a rapid, specific, and highly sensitive prion detection assay. RT-QuIC uses recombinant prion protein to detect minute amounts of PrPSc. RT-QuIC has been successfully used to detect PrPSc from different prion diseases with a variety of substrates including hamster, human, sheep, bank vole, bovine and chimeric forms of prion protein. However, recombinant bovine prion protein has not been used to detect transmissible mink encephalopathy (TME) or to differentiate types of bovine spongiform encephalopathy (BSE) in samples from cattle. We evaluated whether PrPSc from TME and BSE infected cattle can be detected with RT-QuIC using recombinant bovine prion proteins, and optimized the reaction conditions to specifically detect cattle TME and to discriminate between classical and atypical BSE by conversion efficiency. We also found that substrate composed of the disease associated E211K mutant protein can be effective for the detection of TME in cattle and that wild type prion protein appears to be a practical substrate to discriminate between the different types of BSEs.

Vitamin D-Dependent Rickets Type 1B (25-Hydroxylase Deficiency): A Rare Condition or a Misdiagnosed Condition?

PubMed

Molin, Arnaud; Wiedemann, Arnaud; Demers, Nick; Kaufmann, Martin; Do Cao, Jérémy; Mainard, Laurent; Dousset, Brigitte; Journeau, Pierre; Abeguile, Geneviève; Coudray, Nadia; Mittre, Hervé; Richard, Nicolas; Weryha, Georges; Sorlin, Arthur; Jones, Glenville; Kottler, Marie-Laure; Feillet, Francois

2017-09-01

Vitamin D requires a two-step activation by hydroxylation: The first step is catalyzed by hepatic 25-hydroxylase (CYP2R1, 11p15.2) and the second one is catalyzed by renal 1α-hydroxylase (CYP27B1, 12q13.1), which produces the active hormonal form of 1,25-(OH) 2 D. Mutations of CYP2R1 have been associated with vitamin D-dependent rickets type 1B (VDDR1B), a very rare condition that has only been reported to affect 4 families to date. We describe 7 patients from 2 unrelated families who presented with homozygous loss-of-function mutations of CYP2R1. Heterozygous mutations were present in their normal parents. We identified a new c.124_138delinsCGG (p.Gly42_Leu46delinsArg) variation and the previously published c.296T>C (p.Leu99Pro) mutation. Functional in vitro studies confirmed loss-of-function enzymatic activity in both cases. We discuss the difficulties in establishing the correct diagnosis and the specific biochemical pattern, namely, very low 25-OH-D suggestive of classical vitamin D deficiency, in the face of normal/high concentrations of 1,25-(OH) 2 D. Siblings exhibited the three stages of rickets based on biochemical and radiographic findings. Interestingly, adult patients were able to maintain normal mineral metabolism without vitamin D supplementation. One index case presented with a partial improvement with 1alfa-hydroxyvitamin D 3 or alfacalcidol (1α-OH-D 3 ) treatment, and we observed a dramatic increase in the 1,25-(OH) 2 D serum concentration, which indicated the role of accessory 25-hydroxylase enzymes. Lastly, in patients who received calcifediol (25-OH-D 3 ), we documented normal 24-hydroxylase activity (CYP24A1). For the first time, and according to the concept of personalized medicine, we demonstrate dramatic improvements in patients who were given 25-OH-D therapy (clinical symptoms, biochemical data, and bone densitometry). In conclusion, the current study further expands the CYP2R1 mutation spectrum. We note that VDDR1B could be easily mistaken for classical vitamin D deficiency. © 2017 American Society for Bone and Mineral Research. © 2017 American Society for Bone and Mineral Research.

Adrenergic Transmission Facilitates Extinction of Conditional Fear in Mice

ERIC Educational Resources Information Center

Barad, Mark; Cain, Christopher K.; Blouin, Ashley M.

2004-01-01

Extinction of classically conditioned fear, like its acquisition, is active learning, but little is known about its molecular mechanisms. We recently reported that temporal massing of conditional stimulus (CS) presentations improves extinction memory acquisition, and suggested that temporal spacing was less effective because individual CS…

Quantum-holographic and classical Hopfield-like associative nnets: implications for modeling two cognitive modes of consciousness

NASA Astrophysics Data System (ADS)

Rakovic, D.; Dugic, M.

2005-05-01

Quantum bases of consciousness are considered with psychosomatic implications of three front lines of psychosomatic medicine (hesychastic spirituality, holistic Eastern medicine, and symptomatic Western medicine), as well as cognitive implications of two modes of individual consciousness (quantum-coherent transitional and altered states, and classically reduced normal states) alongside with conditions of transformations of one mode into another (considering consciousness quantum-coherence/classical-decoherence acupuncture system/nervous system interaction, direct and reverse, with and without threshold limits, respectively) - by using theoretical methods of associative neural networks and quantum neural holography combined with quantum decoherence theory.

Generalized Quantum Theory of Bianchi IX Cosmologies

NASA Astrophysics Data System (ADS)

Craig, David; Hartle, James

2003-04-01

We apply sum-over-histories generalized quantum theory to the closed homogeneous minisuperspace Bianchi IX cosmological model. We sketch how the probabilities in decoherent sets of alternative, coarse-grained histories of this model universe are calculated. We consider in particular, the probabilities for classical evolution in a suitable coarse-graining. For a restricted class of initial conditions and coarse grainings we exhibit the approximate decoherence of alternative histories in which the universe behaves classically and those in which it does not, illustrating the prediction that these universes will evolve in an approximately classical manner with a probability near unity.

Generalized mutual information and Tsirelson's bound

NASA Astrophysics Data System (ADS)

Wakakuwa, Eyuri; Murao, Mio

2014-12-01

We introduce a generalization of the quantum mutual information between a classical system and a quantum system into the mutual information between a classical system and a system described by general probabilistic theories. We apply this generalized mutual information (GMI) to a derivation of Tsirelson's bound from information causality, and prove that Tsirelson's bound can be derived from the chain rule of the GMI. By using the GMI, we formulate the "no-supersignalling condition" (NSS), that the assistance of correlations does not enhance the capability of classical communication. We prove that NSS is never violated in any no-signalling theory.

Generalized mutual information and Tsirelson's bound

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

Wakakuwa, Eyuri; Murao, Mio

2014-12-04

We introduce a generalization of the quantum mutual information between a classical system and a quantum system into the mutual information between a classical system and a system described by general probabilistic theories. We apply this generalized mutual information (GMI) to a derivation of Tsirelson's bound from information causality, and prove that Tsirelson's bound can be derived from the chain rule of the GMI. By using the GMI, we formulate the 'no-supersignalling condition' (NSS), that the assistance of correlations does not enhance the capability of classical communication. We prove that NSS is never violated in any no-signalling theory.

Aspects of Geodesical Motion with Fisher-Rao Metric: Classical and Quantum

NASA Astrophysics Data System (ADS)

Ciaglia, Florio M.; Cosmo, Fabio Di; Felice, Domenico; Mancini, Stefano; Marmo, Giuseppe; Pérez-Pardo, Juan M.

The purpose of this paper is to exploit the geometric structure of quantum mechanics and of statistical manifolds to study the qualitative effect that the quantum properties have in the statistical description of a system. We show that the end points of geodesics in the classical setting coincide with the probability distributions that minimise Shannon’s entropy, i.e. with distributions of zero dispersion. In the quantum setting this happens only for particular initial conditions, which in turn correspond to classical submanifolds. This result can be interpreted as a geometric manifestation of the uncertainty principle.

Classical r-matrices for the generalised Chern–Simons formulation of 3d gravity

NASA Astrophysics Data System (ADS)

Osei, Prince K.; Schroers, Bernd J.

2018-04-01

We study the conditions for classical r-matrices to be compatible with the generalised Chern–Simons action for 3d gravity. Compatibility means solving the classical Yang–Baxter equations with a prescribed symmetric part for each of the real Lie algebras and bilinear pairings arising in the generalised Chern–Simons action. We give a new construction of r-matrices via a generalised complexification and derive a non-linear set of matrix equations determining the most general compatible r-matrix. We exhibit new families of solutions and show that they contain some known r-matrices for special parameter values.

Scattering of classical and quantum particles by impulsive fields

NASA Astrophysics Data System (ADS)

Balasin, Herbert; Aichelburg, Peter C.

2018-05-01

We investigate the scattering of classical and quantum particles in impulsive backgrounds fields. These fields model short outbursts of radiation propagating with the speed of light. The singular nature of the problem will be accounted for by the use of Colombeau’s generalized function which however give rise to ambiguities. It is the aim of the paper to show that these ambiguities can be overcome by implementing additional physical conditions, which in the non-singular case would be satisfied automatically. As example we discuss the scattering of classical, Klein–Gordon and Dirac particles in impulsive electromagnetic fields.

Comparative study of the in vitro activity of various antifungal drugs against Scedosporium spp. in aerobic and hyperbaric atmosphere versus normal atmosphere.

PubMed

Farina, C; Marchesi, G; Passera, M; Diliberto, C; Russello, G

2012-06-01

Scedosporium spp. have been observed with increasing frequency over the last decade in immunocompromised patients and trauma patients. This mould is often multi-drug resistant and its mortality rate remains very high. The primary goal of this study was to obtain data concerning the in vitro susceptibility of 13 Scedosporium strains comparing the in vitro incubation in aerobic versus hyperbaric conditions. Chemosensitivity of thirteen Scedosporium strains was evaluated after a 72h-incubation in a normoxic (21% O2) normobaric (1 ATA) atmosphere versus a hyperoxic (100% O2) hyperbaric (2-3 ATA), and after a re-incubation at room temperature for an additional 72h. All S. apiospermum and S. prolificans strains showed no growth after incubation in hyperbaric hyperoxic atmosphere. However, when plates were then maintained at room temperature in aerobic conditions, growth was systematically observed from 36 to 96h, and Minimal inhibitory concentration (MIC) values were the same obtained after incubation in aerobic conditions. These results suggest impressive in vitro fungistatic activity of the hyperoxic hyperbaric atmosphere, even if its effect is strictly time-dependent. This preliminary in vitro study has potential clinical relevance because it focuses on examining in vitro combination therapy using hyperoxic hyperbaric conditions plus a single antifungal agent, rather than using combinations of different antifungal drugs, to potentially increase the antifungal activity. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Cinematographic analysis of bovine embryo development in serum-free oviduct-conditioned medium.

PubMed

Grisart, B; Massip, A; Dessy, F

1994-07-01

Development of bovine embryos produced in vitro from the one-cell to the blastocyst stage in serum-free oviduct-conditioned medium was investigated for 8 days consecutively by time-lapse cinematography. Three movies were analysed (130 embryos). The following observations were made. (1) Development under cine-recording conditions was similar to that in a classical incubator. (2) The highest proportion of embryos at the two-cell, three-four-cell, five-eight-cell, 9-16-cell, morula and blastocyst stages were recorded at 34, 46, 61, 115, 149 and 192 h after insemination, respectively. Cleavage asynchrony between blastomeres within individual embryos started at the two-cell stage. (3) The duration of the first three cell cycles was 35 h, 14 h and 11-62 h, respectively. (4) Detailed analysis of 13 embryos revealed that developmental arrest ('Lag-phase') occurred at the four-cell (1 of 13), five-cell (2 of 13), six-cell (3 of 13), seven-cell (3 of 13) or eight-cell stage (4 of 13); this phase lasted about 59 h. Embryos arrested at the eight-cell stage developed into morula-blastocysts (3 of 4) at a higher rate than did those arrested at earlier stages (2 of 9). (5) The faster the embryos cleaved into early stages (two-cell, three-four-cell and five-eight-cell), the higher the probability that they developed into morula-blastocyst: 70% of the embryos reaching the two-cell stage before 30-31 h after insemination developed into morula-blastocyst.(ABSTRACT TRUNCATED AT 250 WORDS)

Multitrace/singletrace formulations and Domain Decomposition Methods for the solution of Helmholtz transmission problems for bounded composite scatterers

NASA Astrophysics Data System (ADS)

Jerez-Hanckes, Carlos; Pérez-Arancibia, Carlos; Turc, Catalin

2017-12-01

We present Nyström discretizations of multitrace/singletrace formulations and non-overlapping Domain Decomposition Methods (DDM) for the solution of Helmholtz transmission problems for bounded composite scatterers with piecewise constant material properties. We investigate the performance of DDM with both classical Robin and optimized transmission boundary conditions. The optimized transmission boundary conditions incorporate square root Fourier multiplier approximations of Dirichlet to Neumann operators. While the multitrace/singletrace formulations as well as the DDM that use classical Robin transmission conditions are not particularly well suited for Krylov subspace iterative solutions of high-contrast high-frequency Helmholtz transmission problems, we provide ample numerical evidence that DDM with optimized transmission conditions constitute efficient computational alternatives for these type of applications. In the case of large numbers of subdomains with different material properties, we show that the associated DDM linear system can be efficiently solved via hierarchical Schur complements elimination.

Scale effect of slip boundary condition at solid–liquid interface

PubMed Central

Nagayama, Gyoko; Matsumoto, Takenori; Fukushima, Kohei; Tsuruta, Takaharu

2017-01-01

Rapid advances in microelectromechanical systems have stimulated the development of compact devices, which require effective cooling technologies (e.g., microchannel cooling). However, the inconsistencies between experimental and classical theoretical predictions for the liquid flow in microchannel remain unclarified. Given the larger surface/volume ratio of microchannel, the surface effects increase as channel scale decreases. Here we show the scale effect of the boundary condition at the solid–liquid interface on single-phase convective heat transfer characteristics in microchannels. We demonstrate that the deviation from classical theory with a reduction in hydraulic diameters is due to the breakdown of the continuum solid–liquid boundary condition. The forced convective heat transfer characteristics of single-phase laminar flow in a parallel-plate microchannel are investigated. Using the theoretical Poiseuille and Nusselt numbers derived under the slip boundary condition at the solid–liquid interface, we estimate the slip length and thermal slip length at the interface. PMID:28256536

Forward and Backward Second-Order Pavlovian Conditioning in Honeybees

ERIC Educational Resources Information Center

Hussaini, Syed Abid; Komischke, Bernhard; Menzel, Randolf; Lachnit, Harald

2007-01-01

Second-order conditioning (SOC) is the association of a neutral stimulus with another stimulus that had previously been combined with an unconditioned stimulus (US). We used classical conditioning of the proboscis extension response (PER) in honeybees ("Apis mellifera") with odors (CS) and sugar (US). Previous SOC experiments in bees were…

Matter, energy, and heat transfer in a classical ballistic atom pump.

PubMed

Byrd, Tommy A; Das, Kunal K; Mitchell, Kevin A; Aubin, Seth; Delos, John B

2014-11-01

A ballistic atom pump is a system containing two reservoirs of neutral atoms or molecules and a junction connecting them containing a localized time-varying potential. Atoms move through the pump as independent particles. Under certain conditions, these pumps can create net transport of atoms from one reservoir to the other. While such systems are sometimes called "quantum pumps," they are also models of classical chaotic transport, and their quantum behavior cannot be understood without study of the corresponding classical behavior. Here we examine classically such a pump's effect on energy and temperature in the reservoirs, in addition to net particle transport. We show that the changes in particle number, of energy in each reservoir, and of temperature in each reservoir vary in unexpected ways as the incident particle energy is varied.

Short- and Long-Term Memories Formed upon Backward Conditioning in Honeybees ("Apis Mellifera")

ERIC Educational Resources Information Center

Felsenberg, Johannes; Plath, Jenny Aino; Lorang, Steven; Morgenstern, Laura; Eisenhardt, Dorothea

2014-01-01

In classical conditioning, the temporal sequence of stimulus presentations is critical for the association between the conditioned stimulus (CS) and the unconditioned stimulus (US). In forward conditioning, the CS precedes the US and is learned as a predictor for the US. Thus it acquires properties to elicit a behavioral response, defined as…

Effects of Swim Stress on Neophobia and Reconditioning Using a Conditioned Taste Aversion Procedure

ERIC Educational Resources Information Center

Walker, Jennifer M.; Ramsey, Ashley K.; Fowler, Stephanie W.; Schachtman, Todd R.

2012-01-01

Previous research has found that swim stress during a classical conditioning trial attenuates conditioned taste aversion (CTA). In the current study, rats were used to examine the effects of inescapable swim stress on the habituation of neophobia to a flavored solution and reacquisition of an extinguished conditioned taste aversion. In Experiment…

X-linked CHARGE-like Abruzzo-Erickson syndrome and classic cleft palate with ankyloglossia result from TBX22 splicing mutations.

PubMed

Pauws, E; Peskett, E; Boissin, C; Hoshino, A; Mengrelis, K; Carta, E; Abruzzo, M A; Lees, M; Moore, G E; Erickson, R P; Stanier, P

2013-04-01

X-linked cleft palate (CPX) is caused by mutations in the gene encoding the TBX22 transcription factor and is known to exhibit phenotypic variability, usually involving either a complete, partial or submucous cleft palate, with or without ankyloglossia. This study hypothesized a possible involvement of TBX22 in a family with X-linked, CHARGE-like Abruzzo-Erickson syndrome, of unknown etiology. The phenotype extends to additional features including sensorineural deafness and coloboma, which are suggested by the Tbx22 developmental expression pattern but not previously associated in CPX patients. A novel TBX22 splice acceptor mutation (c.593-5T>A) was identified that tracked with the phenotype in this family. A novel splice donor variant (c.767+5G>A) and a known canonical splice donor mutation (c.767+1G>A) affecting the same exon were identified in patients with classic CPX phenotypes and were comparatively analyzed using both in silico and in vitro splicing studies. All three variants were predicted to abolish normal mRNA splicing and an in vitro assay indicated that use of alternative splice sites was a likely outcome. Collectively, the data showed the functional effect of several novel intronic splice site variants but most importantly confirms that TBX22 is the gene underlying Abruzzo-Erickson syndrome, expanding the phenotypic spectrum of TBX22 mutations. © 2012 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.

Monocyte Phenotype and Polyfunctionality Are Associated With Elevated Soluble Inflammatory Markers, Cytomegalovirus Infection, and Functional and Cognitive Decline in Elderly Adults

PubMed Central

de Pablo-Bernal, Rebeca Sara; Cañizares, Julio; Rosado, Isaac; Galvá, María Isabel; Alvarez-Ríos, Ana Isabel; Carrillo-Vico, Antonio; Ferrando-Martínez, Sara; Muñoz-Fernández, María Ángeles; Rafii-El-Idrissi Benhnia, Mohammed; Pacheco, Yolanda María; Ramos, Raquel; Leal, Manuel; Ruiz-Mateos, Ezequiel

2016-01-01

Monocytes are mediators of the inflammatory response and include three subsets: classical, intermediate, and nonclassical. Little is known about the phenotypical and functional age-related changes in monocytes and their association with soluble inflammatory biomarkers, cytomegalovirus infection, and functional and mental decline. We assayed the activation ex vivo and the responsiveness to TLR2 and TLR4 agonists in vitro in the three subsets and assessed the intracellular production of IL1-alpha (α), IL1-beta (β), IL-6, IL-8, TNF-α, and IL-10 of elderly adults (median 83 [67–90] years old; n = 20) compared with young controls (median 35 [27–40] years old; n = 20). Ex vivo, the elderly adults showed a higher percentage of classical monocytes that expressed intracellular IL1-α (p = .001), IL1-β (p = .001), IL-6 (p = .002), and IL-8 (p = .007). Similar results were obtained both for the intermediate and nonclassical subsets and in vitro. Polyfunctionality was higher in the elderly adults. The functionality ex vivo was strongly associated with soluble inflammatory markers. The activation phenotype was independently associated with the anti-cytomegalovirus IgG levels and with functional and cognitive decline. These data demonstrate that monocytes are key cell candidates for the source of the high soluble inflammatory levels. Our findings suggest that cytomegalovirus infection might be a driving force in the activation of monocytes and is associated with the functional and cognitive decline. PMID:26286603

Effect of specific amino acid substitutions in the putative fusion peptide of structural glycoprotein E2 on Classical Swine Fever Virus replication

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

Fernández-Sainz, I.J.; Largo, E.; Gladue, D.P.

E2, along with E{sup rns} and E1, is an envelope glycoprotein of Classical Swine Fever Virus (CSFV). E2 is involved in several virus functions: cell attachment, host range susceptibility and virulence in natural hosts. Here we evaluate the role of a specific E2 region, {sup 818}CPIGWTGVIEC{sup 828}, containing a putative fusion peptide (FP) sequence. Reverse genetics utilizing a full-length infectious clone of the highly virulent CSFV strain Brescia (BICv) was used to evaluate how individual amino acid substitutions within this region of E2 may affect replication of BICv. A synthetic peptide representing the complete E2 FP amino acid sequence adoptedmore » a β-type extended conformation in membrane mimetics, penetrated into model membranes, and perturbed lipid bilayer integrity in vitro. Similar peptides harboring amino acid substitutions adopted comparable conformations but exhibited different membrane activities. Therefore, a preliminary characterization of the putative FP {sup 818}CPIGWTGVIEC{sup 828} indicates a membrane fusion activity and a critical role in virus replication. - Highlights: • A putative fusion peptide (FP) region in CSFV E2 protein was shown to be critical for virus growth. • Synthetic FPs were shown to efficiently penetrate into lipid membranes using an in vitro model. • Individual residues in the FP affecting virus replication were identified by reverse genetics. • The same FP residues are also responsible for mediating membrane fusion.« less

The use of classical and operant conditioning in training Aldabra tortoises (Geochelone gigantea), for venipuncture and other, husbandry issues.

PubMed

Weiss, Emily; Wilson, Sandra

2003-01-01

A variety of nonhuman animals in zoo and research settings have been the subjects of classical and operant conditioning techniques. Much of the published work has focused on mammals, husbandry training, and veterinary issues. However, several zoos are training reptiles and birds for similar procedures, but there has been little of this work published. Using positive reinforcement techniques enabled the training of 2 male and 2 female Aldabra tortoises (Geochelone gigantea) to approach a target, hold steady on target, and stretch and hold for venipuncture. This article discusses training techniques, venipuncture sight, and future training.

Conditional symmetries in axisymmetric quantum cosmologies with scalar fields and the fate of the classical singularities

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

Zampeli, Adamantia; Pailas, Theodoros; Terzis, Petros A.

2016-05-01

In this paper, the classical and quantum solutions of some axisymmetric cosmologies coupled to a massless scalar field are studied in the context of minisuperspace approximation. In these models, the singular nature of the Lagrangians entails a search for possible conditional symmetries. These have been proven to be the simultaneous conformal symmetries of the supermetric and the superpotential. The quantization is performed by adopting the Dirac proposal for constrained systems, i.e. promoting the first-class constraints to operators annihilating the wave function. To further enrich the approach, we follow [1] and impose the operators related to the classical conditional symmetries onmore » the wave function. These additional equations select particular solutions of the Wheeler-DeWitt equation. In order to gain some physical insight from the quantization of these cosmological systems, we perform a semiclassical analysis following the Bohmian approach to quantum theory. The generic result is that, in all but one model, one can find appropriate ranges of the parameters, so that the emerging semiclassical geometries are non-singular. An attempt for physical interpretation involves the study of the effective energy-momentum tensor which corresponds to an imperfect fluid.« less

Presence of encircling granulosa cells protects against oxidative stress-induced apoptosis in rat eggs cultured in vitro.

PubMed

Tiwari, Meenakshi; Tripathi, Anima; Chaube, Shail K

2017-01-01

Increased oxidative stress (OS) due to in vitro culture conditions can affect the quality of denuded eggs during various assisted reproductive technologies (ARTs). Presence of intact granulosa cells may protect eggs from OS damage under in vitro culture conditions. The present study was aimed to investigate whether encircling granulosa cells could protect against hydrogen peroxide (H 2 O 2 )-induced egg apoptosis in ovulated cumulus oocyte complexes (COCs) cultured in vitro. The OS was induced by exposing COCs as well as denuded eggs with various concentrations of H 2 O 2 for 3 h in vitro. The morphological changes, total reactive oxygen species (ROS) as well as catalase expression, Bax/Bcl-2, cytochrome c levels and DNA fragmentation were analysed in COCs as well as denuded eggs. Our results suggest that H 2 O 2 treatment induced morphological apoptotic features in a concentration-dependent manner in denuded eggs cultured in vitro. The 20 µM of H 2 O 2 treatment induced OS by elevating total ROS level, reduced catalase and Bcl-2 expression levels with overexpression of Bax and cytochrome c and induced DNA fragmentation in denuded eggs cultured in vitro. The presence of encircling granulosa cells protected H 2 O 2 -induced morphological apoptotic features by preventing the increase of Bax, cytochrome c expression levels and DNA fragmentation in associated egg. However, 20 µM of H 2 O 2 was sufficient to induce peripheral granulosa cell apoptosis in COCs and degeneration in few denuded eggs cultured in vitro. Taken together our data suggest that the presence of encircling granulosa cells could be beneficial to protect ovulated eggs from OS damage under in vitro culture conditions during various ART programs.

"They'd Better Hope for a Lot of Free Parking:" Using "Monopoly" to Teach about Classical Liberalism, Marginalization, and Restorative Justice

ERIC Educational Resources Information Center

Duerringer, Christopher Michael

2013-01-01

The activity outlined here, using the "Monopoly" board game, is designed to illustrate the way that classical liberalism fails to provide justice for societies marked by historical and ongoing oppression. Taking up roles in a game that simulates some of the conditions of late capitalism can help students begin to understand how economic…

The missing link between neurobiology and behavior in Aplysia conditioning.

PubMed

Arvanitogiannis, A

1997-01-01

Over the past decades, a wealth of findings has led to a substantial change in the assumed complexity of classical conditioning. The combined evidence indicates that temporal pairing is neither necessary nor sufficient for the formation of an associative connection. At the same time, studies of model invertebrate nervous systems have allowed us to ask a series of questions about the molecular basis of associative conditioning. The discovery of a pairing-sensitive mechanism in the gill-withdrawal circuitry of Aplysia is regarded as the hallmark of the reductionist approach. This review outlines the insights gathered from behavioral and neurobiological studies. Furthermore, the conceptual frameworks guiding research at the 'what' and 'how' levels of analysis are compared and contrasted. I argue that a rich cognitive view of conditioning has emerged at the 'what' level, whereas the traditional notion of temporal pairing still drives research at the 'how' level. A complete account of classical conditioning has to await the resolving of this discordance.

Are memory traces localized or distributed?

PubMed

Thompson, R F

1991-01-01

Evidence supports the view that "memory traces" are formed in the hippocampus and in the cerebellum in classical conditioning of discrete behavioral responses (e.g. eyeblink conditioning). In the hippocampus, learning results in long-lasting increases in excitability of pyramidal neurons that appear to be localized to these neurons (i.e. changes in membrane properties and receptor function). However, these learning-altered pyramidal neurons are distributed widely throughout CA3 and CA1. Although it plays a key role in certain aspects of classical conditioning, the hippocampus is not necessary for learning and memory of the basic conditioned responses. The cerebellum and its associated brain stem circuitry, on the other hand, does appear to be essential (necessary and sufficient) for learning and memory of the conditioned response. Evidence to date is most consistent with a localized trace in the interpositus nucleus and multiple localized traces in cerebellar cortex, each involving relatively large ensembles of neurons. Perhaps "procedural" memory traces are relatively localized and "declarative" traces more widely distributed.

Dissociating basal forebrain and medial temporal amnesic syndromes: insights from classical conditioning.

PubMed

Myer, Catherine E; Bryant, Deborah; DeLuca, John; Gluck, Mark A

2002-01-01

In humans, anterograde amnesia can result from damage to the medial temporal (MT) lobes (including hippocampus), as well as to other brain areas such as basal forebrain. Results from animal classical conditioning studies suggest that there may be qualitative differences in the memory impairment following MT vs. basal forebrain damage. Specifically, delay eyeblink conditioning is spared after MT damage in animals and humans, but impaired in animals with basal forebrain damage. Recently, we have likewise shown delay eyeblink conditioning impairment in humans with amnesia following anterior communicating artery (ACoA) aneurysm rupture, which damages the basal forebrain. Another associative learning task, a computer-based concurrent visual discrimination, also appears to be spared in MT amnesia while ACoA amnesics are slower to learn the discriminations. Conversely, animal and computational models suggest that, even though MT amnesics may learn quickly, they may learn qualitatively differently from controls, and these differences may result in impaired transfer when familiar information is presented in novel combinations. Our initial data suggests such a two-phase learning and transfer task may provide a double dissociation between MT amnesics (spared initial learning but impaired transfer) and ACoA amnesics (slow initial learning but spared transfer). Together, these emerging data suggest that there are subtle but dissociable differences in the amnesic syndrome following damage to the MT lobes vs. basal forebrain, and that these differences may be most visible in non-declarative tasks such as eyeblink classical conditioning and simple associative learning.

Drug formulations intended for the global market should be tested for stability under tropical climatic conditions.

PubMed

Risha, P G; Vervaet, C; Vergote, G; Bortel, L Van; Remon, J P

2003-06-01

The quality of drugs imported into developing countries having a tropical climate may be adversely affected if their formulations have not been optimized for stability under these conditions. The present study investigated the influence of tropical climate conditions (class IV: 40 degrees C, 75% relative humidity) on the drug content, in vitro dissolution and oral bioavailability of different formulations of two essential drugs marketed in Tanzania: diclofenac sodium and ciprofloxacin tablets. Before and after 3 and 6 months storage under class IV conditions the drug content and in vitro dissolution were evaluated using United States Pharmacopoeia (USP) 24 methods. Following a randomized four-period cross-over study, the pharmacokinetic parameters of drug formulations stored for 3 months under class IV conditions were compared with those stored at ambient conditions. Drug content and drug release from all tested ciprofloxacin formulations were within USP-24 requirements and remained stable during storage at simulated tropical conditions. Oral bioavailability was also not influenced by tropical conditions. The dissolution rate of two diclofenac formulations (Diclo 50 manufactured by Camden and Dicloflame 50 manufactured by Intas) reduced significantly during storage under class IV conditions. After oral administration Camden tablets stored for 3 months under class IV conditions showed a reduction in C(max) (90% CI of C(max) ratio: 0.59 - 0.76). This reduction was smaller than expected based on the in vitro tests. Some drug formulations imported into Tanzania are not optimized for stability in a tropical climate. Manufacturers and regulatory authorities should pay more attention to the WHO recommendations for testing the stability of drugs under tropical climate conditions. Efforts should be made to improve the in vitro tests to better predict the bioavailability.

Drug-induced acne and rose pearl: similarities*

PubMed Central

Pontello Junior, Rubens; Kondo, Rogerio Nabor

2013-01-01

Drug-induced acne is a common skin condition whose classic symptoms can be similar to a rose pearl, as in the case of a male patient presenting with this condition after excessive use of a cream containing corticosteroids. PMID:24474128

Differential IL-1β secretion by monocyte subsets is regulated by Hsp27 through modulating mRNA stability.

PubMed

Hadadi, Eva; Zhang, Biyan; Baidžajevas, Kajus; Yusof, Nurhashikin; Puan, Kia Joo; Ong, Siew Min; Yeap, Wei Hseun; Rotzschke, Olaf; Kiss-Toth, Endre; Wilson, Heather; Wong, Siew Cheng

2016-12-15

Monocytes play a central role in regulating inflammation in response to infection or injury, and during auto-inflammatory diseases. Human blood contains classical, intermediate and non-classical monocyte subsets that each express characteristic patterns of cell surface CD16 and CD14; each subset also has specific functional properties, but the mechanisms underlying many of their distinctive features are undefined. Of particular interest is how monocyte subsets regulate secretion of the apical pro-inflammatory cytokine IL-1β, which is central to the initiation of immune responses but is also implicated in the pathology of various auto-immune/auto-inflammatory conditions. Here we show that primary human non-classical monocytes, exposed to LPS or LPS + BzATP (3'-O-(4-benzoyl)benzyl-ATP, a P2X7R agonist), produce approx. 80% less IL-1β than intermediate or classical monocytes. Despite their low CD14 expression, LPS-sensing, caspase-1 activation and P2X7R activity were comparable in non-classical monocytes to other subsets: their diminished ability to produce IL-1β instead arose from 50% increased IL-1β mRNA decay rates, mediated by Hsp27. These findings identify the Hsp27 pathway as a novel therapeutic target for the management of conditions featuring dysregulated IL-1β production, and represent an advancement in understanding of both physiological inflammatory responses and the pathogenesis of inflammatory diseases involving monocyte-derived IL-1β.

Modulation of opiate-related signaling molecules in morphine-dependent conditioned behavior: conditioned place preference to morphine induces CREB phosphorylation.

PubMed

Morón, José A; Gullapalli, Srinivas; Taylor, Chirisse; Gupta, Achla; Gomes, Ivone; Devi, Lakshmi A

2010-03-01

Opiate addiction is a chronic, relapsing behavioral disorder where learned associations that develop between the abused opiate and the environment in which it is consumed are brought about through Pavlovian (classical) conditioning processes. However, the signaling mechanisms/pathways regulating the mechanisms that underlie the responses to opiate-associated cues or the development of sensitization as a consequence of repeated context-independent administration of opiates are unknown. In this study we examined the phosphorylation levels of various classic signaling molecules in brain regions implicated in addictive behaviors after acute and repeated morphine administration. An unbiased place conditioning protocol was used to examine changes in phosphorylation that are associated with (1) the expression of the rewarding effects of morphine and (2) the sensitization that develops to this effect. We also examined the effects of a delta-receptor antagonist on morphine-induced conditioned behavior and on the phosphorylation of classic signaling molecules in view of data showing that blockade of delta-opioid receptor (deltaOR) prevents the development of sensitization to the rewarding effects of morphine. We find that CREB phosphorylation is specifically induced upon the expression of a sensitized response to morphine-induced conditioned behavior in brain areas related to memory consolidation, such as the hippocampus and cortex. A similar effect is also observed, albeit to a lesser extent, in the case of the GluR1 subunit of AMPA glutamate receptor. These increases in the phosphorylation levels of CREB and pGluR1 are significantly blocked by pretreatment with a deltaOR antagonist. These results indicate a critical role for phospho-CREB, AMPA, and deltaOR activities in mediating the expression of a sensitized response to morphine-dependent conditioned behavior.

Cell cultures in drug discovery and development: The need of reliable in vitro-in vivo extrapolation for pharmacodynamics and pharmacokinetics assessment.

PubMed

Jaroch, Karol; Jaroch, Alina; Bojko, Barbara

2018-01-05

For ethical and cost-related reasons, use of animals for the assessment of mode of action, metabolism and/or toxicity of new drug candidates has been increasingly scrutinized in research and industrial applications. Implementation of the 3 "Rs" 1 ; rule (Reduction, Replacement, Refinement) through development of in silico or in vitro assays has become an essential element of risk assessment. Physiologically based pharmacokinetic (PBPK 2 ) modeling is the most potent in silico tool used for extrapolation of pharmacokinetic parameters to animal or human models from results obtained in vitro. Although, many types of in vitro assays are conducted during drug development, use of cell cultures is the most reliable one. Two-dimensional (2D) cell cultures have been a part of drug development for many years. Nowadays, their role is decreasing in favor of three-dimensional (3D) cell cultures and co-cultures. 3D cultures exhibit protein expression patterns and intercellular junctions that are closer to in vivo states in comparison to classical monolayer cultures. Co-cultures allow for examinations of the mutual influence of different cell lines. However, the complexity and high costs of co-cultures and 3D equipment exclude such methods from high-throughput screening (HTS). 3 In vitro absorption, distribution, metabolism, and excretion assessment, as well as drug-drug interaction (DDI), are usually performed with the use of various cell culture based assays. Progress in in silico and in vitro methods can lead to better in vitro-in vivo extrapolation (IVIVE 4 ) outcomes and have a potential to contribute towards a significant reduction in the number of laboratory animals needed for drug research. As such, concentrated efforts need to be spent towards the development of an HTS in vitro platform with satisfactory IVIVE features. Copyright © 2017 Elsevier B.V. All rights reserved.

Quantization of Chirikov Map and Quantum KAM Theorem.

NASA Astrophysics Data System (ADS)

Shi, Kang-Jie

KAM theorem is one of the most important theorems in classical nonlinear dynamics and chaos. To extend KAM theorem to the regime of quantum mechanics, we first study the quantum Chirikov map, whose classical counterpart provides a good example of KAM theorem. Under resonance condition 2pihbar = 1/N, we obtain the eigenstates of the evolution operator of this system. We find that the wave functions in the coherent state representation (CSR) are very similar to the classical trajectories. In particular, some of these wave functions have wall-like structure at the locations of classical KAM curves. We also find that a local average is necessary for a Wigner function to approach its classical limit in the phase space. We then study the general problem theoretically. Under similar conditions for establishing the classical KAM theorem, we obtain a quantum extension of KAM theorem. By constructing successive unitary transformations, we can greatly reduce the perturbation part of a near-integrable Hamiltonian system in a region associated with a Diophantine number {rm W}_{o}. This reduction is restricted only by the magnitude of hbar.. We can summarize our results as follows: In the CSR of a nearly integrable quantum system, associated with a Diophantine number {rm W}_ {o}, there is a band near the corresponding KAM torus of the classical limit of the system. In this band, a Gaussian wave packet moves quasi-periodically (and remain close to the KAM torus) for a long time, with possible diffusion in both the size and the shape of its wave packet. The upper bound of the tunnelling rate out of this band for the wave packet can be made much smaller than any given power of hbar, if the original perturbation is sufficiently small (but independent of hbar). When hbarto 0, we reproduce the classical KAM theorem. For most near-integrable systems the eigenstate wave function in the above band can either have a wall -like structure or have a vanishing amplitude. These conclusions agree with the numerical results of the quantum Chirikov map.

[Regulation of cellular-mediated immunity by Chenopodi boni henrici herba polysaccharides in hens].

PubMed

Hanganu, Daniela; Dorhoi, Anca; Pintea, Adela; Olah, Neli; Sevastre, B

2010-01-01

The immunomodulatory effect of polysaccharides from Chenopodium bonus-henricus herba was tested on adult hens. Blood samples were harvested aseptically by punction of brachial vein; ability of circulating phagocytes was assessed by the carbon particles phagocytosis test in vitro; while reactivity of peripheral lymphocytes was evaluated by lymphocytes transformation assay in vitro. Polysaharides were dissolved in saline solution and filtered throughout Millipore. Phagocytic indexes (at 15 and 39 minutes) are variable according to polysaharides concentration; phagocytosis increased at 15 minutes for 40 microg/mL and 60 microg/mL, while for 30 minutes the phagocytic index decreased. In lymphocytes transformation assay, Chenopodium bonus-henricus polysaharides, alone, shown no stimulatory effect, and together to the classic mitogen, their influence was variable, but not statistical significant results were seen. Polysaccharides have inconstant effect on phagocytosis, and mainly inhibitory role on lymphocytes proliferation.

Generalized quantum theory of recollapsing homogeneous cosmologies

NASA Astrophysics Data System (ADS)

Craig, David; Hartle, James B.

2004-06-01

A sum-over-histories generalized quantum theory is developed for homogeneous minisuperspace type A Bianchi cosmological models, focusing on the particular example of the classically recollapsing Bianchi type-IX universe. The decoherence functional for such universes is exhibited. We show how the probabilities of decoherent sets of alternative, coarse-grained histories of these model universes can be calculated. We consider in particular the probabilities for classical evolution defined by a suitable coarse graining. For a restricted class of initial conditions and coarse grainings we exhibit the approximate decoherence of alternative histories in which the universe behaves classically and those in which it does not. For these situations we show that the probability is near unity for the universe to recontract classically if it expands classically. We also determine the relative probabilities of quasiclassical trajectories for initial states of WKB form, recovering for such states a precise form of the familiar heuristic “JṡdΣ” rule of quantum cosmology, as well as a generalization of this rule to generic initial states.

Smoothed quantum-classical states in time-irreversible hybrid dynamics

NASA Astrophysics Data System (ADS)

Budini, Adrián A.

2017-09-01

We consider a quantum system continuously monitored in time which in turn is coupled to an arbitrary dissipative classical system (diagonal reduced density matrix). The quantum and classical dynamics can modify each other, being described by an arbitrary time-irreversible hybrid Lindblad equation. Given a measurement trajectory, a conditional bipartite stochastic state can be inferred by taking into account all previous recording information (filtering). Here, we demonstrate that the joint quantum-classical state can also be inferred by taking into account both past and future measurement results (smoothing). The smoothed hybrid state is estimated without involving information from unobserved measurement channels. Its average over recording realizations recovers the joint time-irreversible behavior. As an application we consider a fluorescent system monitored by an inefficient photon detector. This feature is taken into account through a fictitious classical two-level system. The average purity of the smoothed quantum state increases over that of the (mixed) state obtained from the standard quantum jump approach.

MEDIA SERUM LEVELS AND IN VITRO HEPATIC ABSORPTION OF LINDANE

EPA Science Inventory

High plasma protein binding is known to reduce the tissue uptake of chemicals in vivo, but the extent of its importance in vitro is less clear. Experiments were conducted to determine the cellular uptake of lindane in vitro under different conditions. Lindane was selected because...

The erosive potential of soft drinks on enamel surface substrate: an in vitro scanning electron microscopy investigation.

PubMed

Owens, Barry M; Kitchens, Michael

2007-11-01

Using scanning electron and light microscopy, this study qualitatively evaluated the erosive potential of carbonated cola beverages as well as sports and high-energy drinks on enamel surface substrate. Beverages used in this study included: Coca Cola Classic, Diet Coke, Gatorade sports drink, Red Bull high-energy drink, and tap water (control). Extracted human permanent molars free of hypocalcification and/or caries were used in this study. The coronal portion of each tooth was removed and sectioned longitudinally from the buccal to the lingual surface. The crown sections were embedded in acrylic resin, leaving the enamel surfaces exposed. Following finishing and polishing of all surfaces, one side was covered with red nail varnish while the remaining side was exposed to individual beverage immersion for 14 days, 24 hours per day, at 37 degrees C. The specimens were evaluated for enamel surface changes using scanning electron and light microscopy. Enamel specimens exhibited visual surface changes following immersion in the test beverages with Red Bull and Gatorade revealing the most striking surface morphological changes. Specimens subjected to Coca Cola Classic and Diet Coke immersion also displayed irregular post-treatment surface morphology. As verified by microscopic evaluation, all test beverages displayed enamel dissolution in the following order: Red Bull>Gatorade>Coca-Cola Classic>Diet Coke.

The potential effects of pH and buffering capacity on dental erosion.

PubMed

Owens, Barry M

2007-01-01

Soft drink pH (initial pH) has been shown to be a causative factor--but not necessarily the primary initiating factor--of dental erosion. The titratable acidity or buffering capacity has been acknowledged as playing a significant role in the etiology of these lesions. This in vitro study sought to evaluate five different soft drinks (Coca-Cola Classic, Diet Coke, Gatorade sports drink, Red Bull high-energy drink, Starbucks Frappucino coffee drink) and tap water (control) in terms of initial pH and buffering capacity. Initial pH was measured in triplicate for the six beverages. The buffering capacity of each beverage was assessed by measuring the weight (in grams) of 0.10 M sodium hydroxide necessary for titration to pH levels of 5.0, 6.0, 7.0, and 8.3. Coca-Cola Classic produced the lowest mean pH, while Starbucks Frappucino produced the highest pH of any of the drinks except for tap water. Based on statistical analysis using ANOVA and Fisher's post hoc tests at a P < 0.05 level of significance, Red Bull had the highest mean buffering capacity (indicating the strongest potential for erosion of enamel), followed by Gatorade, Coca-Cola Classic, Diet Coke, and Starbucks Frappucino.

Effect of Media Modified To Mimic Cystic Fibrosis Sputum on the Susceptibility of Aspergillus fumigatus, and the Frequency of Resistance at One Center

PubMed Central

Moss, Richard B.; Hernandez, Cathy; Clemons, Karl V.; Martinez, Marife

2016-01-01

Studies of cystic fibrosis (CF) patient exacerbations attributed to Pseudomonas aeruginosa infection have indicated a lack of correlation of outcome with in vitro susceptibility results. One explanation is that the media used for testing do not mimic the airway milieu, resulting in incorrect conclusions. Therefore, media have been devised to mimic CF sputum. Aspergillus fumigatus is the leading fungal pathogen in CF, and susceptibility testing is also used to decide therapeutic choices. We assessed whether media designed to mimic CF sputa would give different fungal susceptibility results than those of classical methods, assaying voriconazole, the most utilized anti-Aspergillus drug in this setting, and 30 CF Aspergillus isolates. The frequency of marked resistance (defined as an MIC of >4 μg/ml) in our CF unit by classical methods is 7%. Studies performed with classical methods and with digested sputum medium, synthetic sputum medium, and artificial sputum medium revealed prominent differences in Aspergillus susceptibility results, as well as growth rate, with each medium. Clinical correlative studies are required to determine which results are most useful in predicting outcome. Comparison of MICs with non-CF isolates also indicated the CF isolates were generally more resistant. PMID:26810647

In vitro propagation, ex vitro rooting and leaf micromorphology of Bauhinia racemosa Lam.: a leguminous tree with medicinal values.

PubMed

Sharma, Udit; Kataria, Vinod; Shekhawat, N S

2017-10-01

A micropropagation system for Bauhinia racemosa Lam. was developed involving axillary shoot proliferation and ex vitro rooting using nodal explants obtained from mature tree. MS medium with 3.0 mg l -1 BA (6-benzyladenine) was optimum for shoot bud induction. For shoot multiplication, mother explants were transferred repeatedly on medium containing low concentration of BA (0.75 mg l -1 ). Number of shoots was increased up to two passages and decreased thereafter. Shoot multiplication was further enhanced on MS medium containing 0.25 mg l -1 each of BA and Kin (Kinetin) with 0.1 mg l -1 of NAA (α-naphthalene acetic acid). Addition of 0.004 mg l -1 TDZ (thidiazuron) increased the rate of shoot multiplication and 21.81 ± 1.26 shoots per culture vessel were obtained. In vitro regenerated shoots were rooted under ex vitro conditions treated with 400 mg l -1 IBA (indole-3-butyric acid) for 7 min on sterile soilrite. After successful hardening in greenhouse, ex vitro rooted plants were transferred to the field conditions with ≈85% of survival rate. Micromorphological changes were observed on leaf surface i.e. development of vein density and trichomes and stomatal appearance, when plants were subjected to environmental conditions. This is the first report on in vitro regeneration of B. racemosa from mature tree.

In vitro cultivation of Gymnophalloides seoi metacercariae (Digenea:Gymnophallidae).

PubMed

Kook, J; Lee, S H; Chai, J Y

1997-03-01

Gymnophalloides seoi is a human intestinal trematode prevalent on southwestern islands in Korea. In the present study, we investigated whether G. seoi metacercariae can grow and develop into adults by in vitro cultivation. The metacercariae were obtained from naturally infected oysters, and cultured in vitro for 5 days under three conditions; 37 degrees C/5% CO2, 41 degrees C/8% CO2, or 41 degrees C/5% CO2, in NCTC 109 complete media containing 20% FBS and 1% antibiotics-antimycotics. The degree of worm growth and development was compared with that grown in vivo of C3H mice. The length of the worms cultivated in vitro was 200-300 microns not significantly different from metacercariae, whereas the length of the worms recovered from C3H mice was significantly larger, 300-400 microns. The worms produced eggs when grown in C3H mice or cultured in vitro for 2 days under 41 degrees C/8% CO2 or 41 degrees C/5% CO2, but not when cultured under 37 degrees C/5% CO2. Among the in vitro conditions, 41 degrees C/5% CO2 was best for egg production, although the number of eggs was about half of worms obtained from C3H mice. In conclusion, in vitro cultivation of G. seoi metacercariae into egg-producing adults was partially successful under culture conditions of 41 degrees C/5% CO2 or 41 degrees C/8% CO2.

Riemann surfaces of complex classical trajectories and tunnelling splitting in one-dimensional systems

NASA Astrophysics Data System (ADS)

Harada, Hiromitsu; Mouchet, Amaury; Shudo, Akira

2017-10-01

The topology of complex classical paths is investigated to discuss quantum tunnelling splittings in one-dimensional systems. Here the Hamiltonian is assumed to be given as polynomial functions, so the fundamental group for the Riemann surface provides complete information on the topology of complex paths, which allows us to enumerate all the possible candidates contributing to the semiclassical sum formula for tunnelling splittings. This naturally leads to action relations among classically disjoined regions, revealing entirely non-local nature in the quantization condition. The importance of the proper treatment of Stokes phenomena is also discussed in Hamiltonians in the normal form.

Eye-Blink Conditioning Is Associated with Changes in Synaptic Ultrastructure in the Rabbit Interpositus Nuclei

ERIC Educational Resources Information Center

Weeks, Andrew C. W.; Connor, Steve; Hinchcliff, Richard; LeBoutillier, Janelle C.; Thompson, Richard F.; Petit, Ted L.

2007-01-01

Eye-blink conditioning involves the pairing of a conditioned stimulus (usually a tone) to an unconditioned stimulus (air puff), and it is well established that an intact cerebellum and interpositus nucleus, in particular, are required for this form of classical conditioning. Changes in synaptic number or structure have long been proposed as a…

In vitro fabrication of a tissue engineered human cardiovascular patch for future use in cardiovascular surgery.

PubMed

Yang, Chao; Sodian, Ralf; Fu, Ping; Lüders, Cora; Lemke, Thees; Du, Jing; Hübler, Michael; Weng, Yuguo; Meyer, Rudolf; Hetzer, Roland

2006-01-01

One approach to tissue engineering has been the development of in vitro conditions for the fabrication of functional cardiovascular structures intended for implantation. In this experiment, we developed a pulsatile flow system that provides biochemical and biomechanical signals in order to regulate autologous, human patch-tissue development in vitro. We constructed a biodegradable patch scaffold from porous poly-4-hydroxy-butyrate (P4HB; pore size 80 to 150 microm). The scaffold was seeded with pediatric aortic cells. The cell-seeded patch constructs were placed in a self-developed bioreactor for 7 days to observe potential tissue formation under dynamic cell culture conditions. As a control, cell-seeded scaffolds were not conditioned in the bioreactor system. After maturation in vitro, the analysis of the tissue engineered constructs included biochemical, biomechanical, morphologic, and immunohistochemical examination. Macroscopically, all tissue engineered constructs were covered by cells. After conditioning in the bioreactor, the cells were mostly viable, had grown into the pores, and had formed tissue on the patch construct. Electron microscopy showed confluent smooth surfaces. Additionally, we demonstrated the capacity to generate collagen and elastin under in vitro pulsatile flow conditions in biochemical examination. Biomechanical testing showed mechanical properties of the tissue engineered human patch tissue without any statistical differences in strength or resistance to stretch between the static controls and the conditioned patches. Immunohistochemical examination stained positive for alpha smooth muscle actin, collagen type I, and fibronectin. There was minor tissue formation in the nonconditioned control samples. Porous P4HB may be used to fabricate a biodegradable patch scaffold. Human vascular cells attached themselves to the polymeric scaffold, and extracellular matrix formation was induced under controlled biomechanical and biodynamic stimuli in a self-developed pulsatile bioreactor system.

Mauritia flexuosa Presents In Vitro and In Vivo Antiplatelet and Antithrombotic Activities

PubMed Central

Fuentes, Eduardo; Rodríguez-Pérez, Wilson; Guzmán, Luis; Alarcón, Marcelo; Navarrete, Simón; Forero-Doria, Oscar; Palomo, Iván

2013-01-01

Fruit from the palm Mauritia flexuosa is one of the most important species in Peru, Venezuela, Brazil, Colombia, Bolivia, and Guyana. The present study aimed to investigate the antiplatelet and antithrombotic activities of oil extracted from Mauritia flexuosa. The fatty acid contents were determined by gas chromatography—mass spectrometry. Oil extract of peel of Mauritia flexuosa was extracted by soxhlet extraction. The oil extract inhibited platelet secretion and aggregation induced by ADP, collagen, and TRAP-6 by a concentration-dependent way (0.1 to 1 mg/mL) without the participation of the adenylyl cyclase pathway and diminished platelet rolling and firm adhesion under flow conditions. Furthermore, the oil extract induced a marked increase in the rolling speed of leukocytes retained on the platelet surface, reflecting a reduction of rolling and less adhesion. At the concentrations used, the oil extract significantly decreased platelet release of sP-selectin, an atherosclerotic-related inflammatory mediator. Oil extract inhibited thrombus growth at the same concentration as that of aspirin, a classical reference drug. Finally, the data presented herein also demonstrate for the first time to our knowledge the protective effect of oil extracted from Mauritia flexuosa on platelet activation and thrombosis formation. PMID:24454503

Study of serum interaction with a cationic nanoparticle: Implications for in vitro endocytosis, cytotoxicity and genotoxicity.

PubMed

Merhi, Maysaloun; Dombu, Christophe Youta; Brient, Alizée; Chang, Jiang; Platel, Anne; Le Curieux, Frank; Marzin, Daniel; Nesslany, Fabrice; Betbeder, Didier

2012-02-14

We used well-characterized and positively charged nanoparticles (NP(+)) to investigate the importance of cell culture conditions, specifically the presence of serum and proteins, on NP(+) physicochemical characteristics, and the consequences for their endocytosis and genotoxicity in bronchial epithelial cells (16HBE14o-). NP(+) surface charge was significantly reduced, proportionally to NP(+)/serum and NP(+)/BSA ratios, while NP(+) size was not modified. Microscopy studies showed high endocytosis of NP(+) in 16HBE14o-, and serum/proteins impaired this internalization in a dose-dependent manner. Toxicity studies showed no cytotoxicity, even for very high doses of NP(+). No genotoxicity was observed with classic comet assay while primary oxidative DNA damage was observed when using the lesion-specific repair enzyme, formamidopyrimidine DNA-glycosylase (FPG). The micronucleus test showed NP(+) genotoxicity only for very high doses that cannot be attained in vivo. The low toxicity of these NP(+) might be explained by their high exocytosis from 16HBE14o- cells. Our results confirm the importance of serum and proteins on nanoparticles endocytosis and genotoxicity. Copyright © 2011 Elsevier B.V. All rights reserved.

Anti-inflammatory and Antihistaminic Study of a Unani Eye Drop Formulation.

PubMed

Abdul, Latif; Abdul, Razique; Sukul, R R; Nazish, Siddiqui

2010-01-01

The Unani eye drop is an ophthalmic formulation prepared for its beneficial effects in the inflammatory and allergic conditions of the eyes. In the present study, the Unani eye drop formulation was prepared and investigated for its anti-inflammatory and antihistaminic activity, using in vivo and in vitro experimental models respectively. The Unani eye drop formulation exhibited significant anti-inflammatory activity in turpentine liniment-induced ocular inflammation in rabbits. The preparation also showed antihistaminic activity in isolated guinea-pig ileum. The anti-inflammatory and antihistaminic activity of eye drop may be due to presence of active ingredients in the formulation. Although there are many drugs in Unani repository which are mentioned in classical books or used in Unani clinical practice effectively in treatment of eye diseases by various Unani physicians. Inspite of the availability of vast literature, there is a dearth of commercial Unani ocular preparations. So, keeping this in mind, the eye drop formulation was prepared and its anti-inflammatory and antihistaminic activity was carried out in animal models. Thus, in view of the importance of alternative anti-inflammatory and antiallergic drugs, it becomes imperative to bring these indigenous drugs to the front foot and evaluate their activities.

A Modified Gibson Assembly Method for Cloning Large DNA Fragments with High GC Contents.

PubMed

Li, Lei; Jiang, Weihong; Lu, Yinhua

2018-01-01

Gibson one-step, isothermal assembly method (Gibson assembly) can be used to efficiently assemble large DNA molecules by in vitro recombination involving a 5'-exonuclease, a DNA polymerase and a DNA ligase. In the past few years, this robust DNA assembly method has been widely applied to seamlessly construct genes, genetic pathways and even entire genomes. Here, we expand this method to clone large DNA fragments with high GC contents, such as antibiotic biosynthetic gene clusters from Streptomyces . Due to the low isothermal condition (50 °C) in the Gibson reaction system, the complementary overlaps with high GC contents are proposed to easily form mismatched linker pairings, which leads to low assembly efficiencies mainly due to vector self-ligation. So, we modified this classic method by the following two steps. First, a pair of universal terminal single-stranded DNA overhangs with high AT contents are added to the ends of the BAC vector. Second, two restriction enzyme sites are introduced into the respective sides of the designed overlaps to achieve the hierarchical assembly of large DNA molecules. The optimized Gibson assembly method facilitates fast acquisition of large DNA fragments with high GC contents from Streptomyces.

Enamel Thickness before and after Orthodontic Treatment Analysed in Optical Coherence Tomography

PubMed Central

Koprowski, Robert; Safranow, Krzysztof; Woźniak, Krzysztof

2017-01-01

Despite the continuous development of materials and techniques of adhesive bonding, the basic procedure remains relatively constant. The technique is based on three components: etching substance, adhesive system, and composite material. The use of etchants during bonding orthodontic brackets carries the risk of damage to the enamel. Therefore, the article examines the effect of the manner of enamel etching on its thickness before and after orthodontic treatment. The study was carried out in vitro on a group of 80 teeth. It was divided into two subgroups of 40 teeth each. The procedure of enamel etching was performed under laboratory conditions. In the first subgroup, the classic method of enamel etching and the fifth-generation bonding system were used. In the second subgroup, the seventh-generation (self-etching) bonding system was used. In both groups, metal orthodontic brackets were fixed and the enamel was cleaned with a cutter fixed on the micromotor after their removal. Before and after the treatment, two-dimensional optical coherence tomography scans were performed. The enamel thickness was assessed on the two-dimensional scans. The average enamel thickness in both subgroups was not statistically significant. PMID:28243604

HO-1-mediated macroautophagy: a mechanism for unregulated iron deposition in aging and degenerating neural tissues.

PubMed

Zukor, Hillel; Song, Wei; Liberman, Adrienne; Mui, Jeannie; Vali, Hojatollah; Fillebeen, Carine; Pantopoulos, Kostas; Wu, Ting-Di; Guerquin-Kern, Jean-Luc; Schipper, Hyman M

2009-05-01

Oxidative stress, deposition of non-transferrin iron, and mitochondrial insufficiency occur in the brains of patients with Alzheimer disease (AD) and Parkinson disease (PD). We previously demonstrated that heme oxygenase-1 (HO-1) is up-regulated in AD and PD brain and promotes the accumulation of non-transferrin iron in astroglial mitochondria. Herein, dynamic secondary ion mass spectrometry (SIMS) and other techniques were employed to ascertain (i) the impact of HO-1 over-expression on astroglial mitochondrial morphology in vitro, (ii) the topography of aberrant iron sequestration in astrocytes over-expressing HO-1, and (iii) the role of iron regulatory proteins (IRP) in HO-1-mediated iron deposition. Astroglial hHO-1 over-expression induced cytoplasmic vacuolation, mitochondrial membrane damage, and macroautophagy. HO-1 promoted trapping of redox-active iron and sulfur within many cytopathological profiles without impacting ferroportin, transferrin receptor, ferritin, and IRP2 protein levels or IRP1 activity. Thus, HO-1 activity promotes mitochondrial macroautophagy and sequestration of redox-active iron in astroglia independently of classical iron mobilization pathways. Glial HO-1 may be a rational therapeutic target in AD, PD, and other human CNS conditions characterized by the unregulated deposition of brain iron.

Mauritia flexuosa Presents In Vitro and In Vivo Antiplatelet and Antithrombotic Activities.

PubMed

Fuentes, Eduardo; Rodríguez-Pérez, Wilson; Guzmán, Luis; Alarcón, Marcelo; Navarrete, Simón; Forero-Doria, Oscar; Palomo, Iván

2013-01-01

Fruit from the palm Mauritia flexuosa is one of the most important species in Peru, Venezuela, Brazil, Colombia, Bolivia, and Guyana. The present study aimed to investigate the antiplatelet and antithrombotic activities of oil extracted from Mauritia flexuosa. The fatty acid contents were determined by gas chromatography-mass spectrometry. Oil extract of peel of Mauritia flexuosa was extracted by soxhlet extraction. The oil extract inhibited platelet secretion and aggregation induced by ADP, collagen, and TRAP-6 by a concentration-dependent way (0.1 to 1 mg/mL) without the participation of the adenylyl cyclase pathway and diminished platelet rolling and firm adhesion under flow conditions. Furthermore, the oil extract induced a marked increase in the rolling speed of leukocytes retained on the platelet surface, reflecting a reduction of rolling and less adhesion. At the concentrations used, the oil extract significantly decreased platelet release of sP-selectin, an atherosclerotic-related inflammatory mediator. Oil extract inhibited thrombus growth at the same concentration as that of aspirin, a classical reference drug. Finally, the data presented herein also demonstrate for the first time to our knowledge the protective effect of oil extracted from Mauritia flexuosa on platelet activation and thrombosis formation.

Fibroblast growth factor receptor signaling in kidney and lower urinary tract development

PubMed Central

Walker, Kenneth A; Sims-Lucas, Sunder; Bates, Carlton M.

2015-01-01

Fibroblast growth factor receptors (FGFRs) and FGF ligands are highly expressed in the developing kidney and lower urinary tract. Several classic studies showed many effects of exogenous FGF ligands on embryonic renal tissues in vitro and in vivo. Another older landmark publication showed that mice with a dominant negative Fgfr fragment had severe renal dysplasia. Together these studies revealed the importance of FGFR signaling in kidney and lower urinary tract development. With the advent of modern gene targeting techniques, including conditional knockout approaches, several publications have revealed critical roles for FGFR signaling in many lineages of the kidney and lower urinary tract at different stages of development. FGFR signaling has been shown to be critical for early metanephric mesenchymal patterning, Wolffian duct patterning including induction of the ureteric bud, ureteric bud branching morphogenesis, nephron progenitor survival and nephrogenesis, and bladder mesenchyme patterning. FGFRs pattern these tissues by interacting with many other growth factor signaling pathways. Moreover, the many genetic Fgfr and Fgf animal models have structural defects mimicking numerous congenital anomalies of the kidney and urinary tract seen in humans. Finally, many studies have shown how FGFR signaling is critical for kidney and lower urinary tract patterning in humans. PMID:26293980

Fibroblast growth factor receptor signaling in kidney and lower urinary tract development.

PubMed

Walker, Kenneth A; Sims-Lucas, Sunder; Bates, Carlton M

2016-06-01

Fibroblast growth factor receptors (FGFRs) and FGF ligands are highly expressed in the developing kidney and lower urinary tract. Several classic studies showed many effects of exogenous FGF ligands on embryonic renal tissues in vitro and in vivo. Another older landmark publication showed that mice with a dominant negative Fgfr fragment had severe renal dysplasia. Together, these studies revealed the importance of FGFR signaling in kidney and lower urinary tract development. With the advent of modern gene targeting techniques, including conditional knockout approaches, several publications have revealed critical roles for FGFR signaling in many lineages of the kidney and lower urinary tract at different stages of development. FGFR signaling has been shown to be critical for early metanephric mesenchymal patterning, Wolffian duct patterning including induction of the ureteric bud, ureteric bud branching morphogenesis, nephron progenitor survival and nephrogenesis, and bladder mesenchyme patterning. FGFRs pattern these tissues by interacting with many other growth factor signaling pathways. Moreover, the many genetic Fgfr and Fgf animal models have structural defects mimicking numerous congenital anomalies of the kidney and urinary tract seen in humans. Finally, many studies have shown how FGFR signaling is critical for kidney and lower urinary tract patterning in humans.

Probabilities for time-dependent properties in classical and quantum mechanics

NASA Astrophysics Data System (ADS)

Losada, Marcelo; Vanni, Leonardo; Laura, Roberto

2013-05-01

We present a formalism which allows one to define probabilities for expressions that involve properties at different times for classical and quantum systems and we study its lattice structure. The formalism is based on the notion of time translation of properties. In the quantum case, the properties involved should satisfy compatibility conditions in order to obtain well-defined probabilities. The formalism is applied to describe the double-slit experiment.

A Frequency-Domain Adaptive Matched Filter for Active Sonar Detection.

PubMed

Zhao, Zhishan; Zhao, Anbang; Hui, Juan; Hou, Baochun; Sotudeh, Reza; Niu, Fang

2017-07-04

The most classical detector of active sonar and radar is the matched filter (MF), which is the optimal processor under ideal conditions. Aiming at the problem of active sonar detection, we propose a frequency-domain adaptive matched filter (FDAMF) with the use of a frequency-domain adaptive line enhancer (ALE). The FDAMF is an improved MF. In the simulations in this paper, the signal to noise ratio (SNR) gain of the FDAMF is about 18.6 dB higher than that of the classical MF when the input SNR is -10 dB. In order to improve the performance of the FDAMF with a low input SNR, we propose a pre-processing method, which is called frequency-domain time reversal convolution and interference suppression (TRC-IS). Compared with the classical MF, the FDAMF combined with the TRC-IS method obtains higher SNR gain, a lower detection threshold, and a better receiver operating characteristic (ROC) in the simulations in this paper. The simulation results show that the FDAMF has higher processing gain and better detection performance than the classical MF under ideal conditions. The experimental results indicate that the FDAMF does improve the performance of the MF, and can adapt to actual interference in a way. In addition, the TRC-IS preprocessing method works well in an actual noisy ocean environment.

Bromelain enzyme from pineapple: in vitro activity study under different micropropagation conditions.

PubMed

Vilanova Neta, Jaci Lima; da Silva Lédo, Ana; Lima, Aloisio André Bonfim; Santana, José Carlos Curvelo; Leite, Nadjma Souza; Ruzene, Denise Santos; Silva, Daniel Pereira; de Souza, Roberto Rodrigues

2012-09-01

The aim of this work was to evaluate the activity of bromelain in pineapple plants (Ananas comosus var. Comosus), Pérola cultivar, produced in vitro in different culture conditions. This enzyme, besides its pharmacological effects, is also employed in food industries, such as breweries and meat processing. In this work, the enzymatic activity was evaluated in the tissues of leaves and stems of plants grown in culture medium without plant growth regulator. The most significant levels of bromelain were observed in leaf tissue after 4 months of culture in vitro in medium with a filter paper bridge, followed by medium gelled by the agar. The results of this study, regarding the different structures of the pineapple (leaves and stems) in vitro showed that the activity of bromelain varied depending on the culture conditions, the time and structure of which was quantified, ensuring a viable strategy in the production of seedlings with high levels of bromelain in subsequent phases of micropropagation.

T cell regulation in microgravity - The current knowledge from in vitro experiments conducted in space, parabolic flights and ground-based facilities

NASA Astrophysics Data System (ADS)

Hauschild, Swantje; Tauber, Svantje; Lauber, Beatrice; Thiel, Cora S.; Layer, Liliana E.; Ullrich, Oliver

2014-11-01

Dating back to the Apollo and Skylab missions, it has been reported that astronauts suffered from bacterial and viral infections during space flight or after returning to Earth. Blood analyses revealed strongly reduced capability of human lymphocytes to become active upon mitogenic stimulation. Since then, a large number of in vitro studies on human immune cells have been conducted in space, in parabolic flights, and in ground-based facilities. It became obvious that microgravity affects cell morphology and important cellular functions. Observed changes include cell proliferation, the cytoskeleton, signal transduction and gene expression. This review gives an overview of the current knowledge of T cell regulation under altered gravity conditions obtained by in vitro studies with special emphasis on the cell culture conditions used. We propose that future in vitro experiments should follow rigorous standardized cell culture conditions, which allows better comparison of the results obtained in different flight- and ground-based experiment platforms.

Standardization of an in vitro Model for Evaluating the Bioavailability of Topically Applied Compounds on Damaged Skin: Application to Sunscreen Analysis.

PubMed

Jacques-Jamin, Carine; Jeanjean-Miquel, Corinne; Domergue, Anaïs; Bessou-Touya, Sandrine; Duplan, Hélène

2017-01-01

Information is lacking on the dermal penetration of topically applied formulations on in vitro skin models, under conditions where the stratum corneum (SC) is damaged. Therefore, we have developed a standardized in vitro barrier-disrupted skin model using tape stripping. Different tape stripping conditions were evaluated using histology, transepidermal water loss, infrared densitometry, and caffeine absorption. The effects of tape stripping were comparable using pig and human skin. Optimized conditions were used to test the effect of SC damage and UV irradiation on the absorption of an UV filter combination present in a sunscreen. The bioavailability of the filters was extremely low regardless of the extent of skin damage, suggesting bioavailability would not be increased if the consumer applied the sunscreen to sun-damaged skin. This standardized in vitro methodology using pig or human skin for damaged skin will add valuable information for the safety assessment of topically applied products. © 2017 S. Karger AG, Basel.

Medium-term in vitro storage as a complementary germplasm preservation technique

USDA-ARS?s Scientific Manuscript database

A Germplasm preservation of vegetatively propagated crops may be accomplished using a range of old and new technologies. Field collections, potted plants, or some cases whole plants stored under cool to cold conditions are complemented by in vitro culture, in vitro storage, and cryopreservation. The...

The Birth and Death of Redundancy in Decoherence and Quantum Darwinism

NASA Astrophysics Data System (ADS)

Riedel, Charles; Zurek, Wojciech; Zwolak, Michael

2012-02-01

Understanding the quantum-classical transition and the identification of a preferred classical domain through quantum Darwinism is based on recognizing high-redundancy states as both ubiquitous and exceptional. They are produced ubiquitously during decoherence, as has been demonstrated by the recent identification of very general conditions under which high-redundancy states develop. They are exceptional in that high-redundancy states occupy a very narrow corner of the global Hilbert space; states selected at random are overwelming likely to exhibit zero redundancy. In this letter, we examine the conditions and time scales for the transition from high-redundancy states to zero-redundancy states in many-body dynamics. We identify sufficient condition for the development of redundancy from product states and show that the destruction of redundancy can be accomplished even with highly constrained interactions.

Planckian charged black holes in ultraviolet self-complete quantum gravity

NASA Astrophysics Data System (ADS)

Nicolini, Piero

2018-03-01

We present an analysis of the role of the charge within the self-complete quantum gravity paradigm. By studying the classicalization of generic ultraviolet improved charged black hole solutions around the Planck scale, we showed that the charge introduces important differences with respect to the neutral case. First, there exists a family of black hole parameters fulfilling the particle-black hole condition. Second, there is no extremal particle-black hole solution but quasi extremal charged particle-black holes at the best. We showed that the Hawking emission disrupts the condition of particle-black hole. By analyzing the Schwinger pair production mechanism, the charge is quickly shed and the particle-black hole condition can ultimately be restored in a cooling down phase towards a zero temperature configuration, provided non-classical effects are taken into account.

Possible conditioned stimulus pathway for classical eyelid conditioning in rabbits. I. Anatomical evidence for direct projections from the pontine nuclei to the cerebellar interpositus nucleus.

PubMed

Steinmetz, J E; Sengelaub, D R

1992-03-01

Wheat germ agglutinin and cholera toxin-conjugated horseradish peroxidase (HRP) were used to retrogradely and anterogradely trace connectivity between the lateral regions of the pontine nuclei and the anterior interpositus nucleus of the cerebellum in rabbits. Projections from the pontine nuclei were found to terminate in the anterior interpositus nucleus and the interpositus was found to send projections to the pontine nuclei. Projections from the nucleus reticularis tegmenti pontis, dorsal accessory inferior olive, and Larsell's lobule HVI of the cerebellum were also found to terminate in the interpositus nucleus and projections from the interpositus nucleus to the inferior olivary complex were observed. The projections from brain stem regions to the interpositus nucleus are discussed as possible pathways that are involved in classical eyelid conditioning.

Dental health and alimentation among the Quintana Roo Mayas: coastal and inland sites of the classic-postclassic periods.

PubMed

Ortega-Muñoz, Allan

2015-01-01

The goal of this study is to compare both dental and skeletal stress indicators of the Classic and Postclassic coastal and inland sites of the State of Quintana Roo, Mexico. The hypothesis is that coastal populations will show osteo and dental pathologies characteristic of a primarily marine food source combined with a diet of horticultural resources. This kind of alimentation provides people with less environmental stress and therefore a better health status. However, over time, in the Postclassic period, the health conditions deteriorated among both coastal and inland inhabitants, according to the hierarchization of the society, militarization, and commercial activities of all the coastal sites. The sample was drawn from 19 sites (196 individuals of both sexes) from the east coast of the Yucatan Peninsula, as well as from inland localities within the boundaries of Quintana Roo. Both dental and osteological stress indicators were analyzed, and crosstabs were applied for absolute and relative frequencies and their corresponding χ(2) and F Fisher analyses. The osteopathological index of the coastal and inland sites of the Classic period were compared over time between the Classic coastal inhabitants and the Postclassic coastal inhabitants so as to understand how life conditions changed over time. The Mantel-Haenszel odds ratio, with the crosstabs controlling for sex (males and females), was also carried out. There are low frequencies of dental pathologies and anemia present in both the coastal and inland populations of Quintana Roo in the Classic and Postclassic times. Only the presence of periostitis is highly common in both types of site, and this is the only indicator with significant differences. The dental pathologies, anemia and periostitis, in general, present a slight upward trend in both the coastal and inland populations over time. The coastal populations have fewer frequencies of the above than the inland sites whilst, in the Postclassic period, both the coastal and inland sites register increased frequencies of all the indicators. Linear enamel hypoplasia (LEH) is the only indicator that does not follow this tendency. The analyzed indicators are in accord with the general tendency reported in the literature. The results revealed a general trend whereby the Classic inland sites display poorer life conditions than the Classic coastal sites. In the Postclassic period, this pattern changed because the frequencies of all stress indicators increased. The explanations regarding this tendency are related to the differential access to food resources between regions; coastal people had a varied diet and better sources of protein, taking into account the culture of alimentation, the type, and the sources (in general, fish) that have an important impact on the absorption of micronutrients and therefore greater impact on local health conditions. Also, it is plausible that they were able to access imported food through commerce (such as meat and vegetables/corn). The decline in health of the coastal people in the Postclassic period was probably associated with social stratification, increasing militarism, changes in the economic corpus, new pathogens, and the decline of the power structures prevailing throughout the Classic period. © 2015 Wiley Periodicals, Inc.

Classical dendritic cells mediate fibrosis directly via the retinoic acid pathway in severe eye allergy

PubMed Central

Ahadome, Sarah D.; Mathew, Rose; Reyes, Nancy J.; Mettu, Priyatham S.; Cousins, Scott W.; Calder, Virginia L.; Saban, Daniel R.

2016-01-01

Fibrosis is a shared end-stage pathway to lung, liver, and heart failure. In the ocular mucosa (conjunctiva), fibrosis leads to blindness in trachoma, pemphigoid, and allergy. The indirect fibrogenic role of DCs via T cell activation and inflammatory cell recruitment is well documented. However, here we demonstrate that DCs can directly induce fibrosis. In the mouse model of allergic eye disease (AED), classical CD11b+ DCs in the ocular mucosa showed increased activity of aldehyde dehydrogenase (ALDH), the enzyme required for retinoic acid synthesis. In vitro, CD11b+ DC–derived ALDH was associated with 9-cis-retinoic acid ligation to retinoid x receptor (RXR), which induced conjunctival fibroblast activation. In vivo, stimulating RXR led to rapid onset of ocular mucosal fibrosis, whereas inhibiting ALDH activity in DCs or selectively depleting DCs markedly reduced fibrosis. Collectively, these data reveal a profibrotic ALDH-dependent pathway by DCs and uncover a role for DC retinoid metabolism. PMID:27595139

Traction test of temporary dental cements

PubMed Central

Millan-Martínez, Diego; Fons-Font, Antonio; Agustín-Panadero, Rubén; Fernández-Estevan, Lucía

2017-01-01

Background Classic self-curing temporary cements obstruct the translucence of provisional restorations. New dual-cure esthetic temporary cements need investigation and comparison with classic cements to ensure that they are equally retentive and provide adequate translucence. The objective is to analyze by means of traction testing in a in vitro study the retention of five temporary cements. Material and Methods Ten molars were prepared and ten provisional resin restorations were fabricated using CAD-CAM technology (n=10). Five temporary cements were selected: self-curing temporary cements, Dycal (D), Temp Bond (TB), Temp Bond Non Eugenol (TBNE); dual-curing esthetic cements Temp Bond Clear (TBC) and Telio CS link (TE). Each sample underwent traction testing, both with thermocycling (190 cycles at 5-55º) and without thermocycling. Results TE and TBC obtained the highest traction resistance values. Thermocycling reduced the resistance of all cements except TBC. Conclusions The dual-cure esthetic cements tested provided optimum outcomes for bonding provisional restorations. Key words:Temporary dental cements, cements resistance. PMID:28469824

Both Intrinsic Substrate Preference and Network Context Contribute to Substrate Selection of Classical Tyrosine Phosphatases*

PubMed Central

Tinti, Michele; Paoluzi, Serena; Santonico, Elena; Masch, Antonia; Schutkowski, Mike

2017-01-01

Reversible tyrosine phosphorylation is a widespread post-translational modification mechanism underlying cell physiology. Thus, understanding the mechanisms responsible for substrate selection by kinases and phosphatases is central to our ability to model signal transduction at a system level. Classical protein-tyrosine phosphatases can exhibit substrate specificity in vivo by combining intrinsic enzymatic specificity with the network of protein-protein interactions, which positions the enzymes in close proximity to their substrates. Here we use a high throughput approach, based on high density phosphopeptide chips, to determine the in vitro substrate preference of 16 members of the protein-tyrosine phosphatase family. This approach helped identify one residue in the substrate binding pocket of the phosphatase domain that confers specificity for phosphopeptides in a specific sequence context. We also present a Bayesian model that combines intrinsic enzymatic specificity and interaction information in the context of the human protein interaction network to infer new phosphatase substrates at the proteome level. PMID:28159843

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

Aratani, Satoko; Oishi, Takayuki; Fujita, Hidetoshi

RNA helicase A (RHA), an ATPase/helicase, regulates the gene expression at various steps including transcriptional activation and RNA processing. RHA is known to shuttle between the nucleus and cytoplasm. We identified the nuclear localization signal (NLS) of RHA and analyzed the nuclear import mechanisms. The NLS of RHA (RHA-NLS) consisting of 19 amino acid residues is highly conserved through species and does not have the consensus classical NLS. In vitro nuclear import assays revealed that the nuclear import of RHA was Ran-dependent and mediated with the classical importin-{alpha}/{beta}-dependent pathway. The binding assay indicated that the basic residues in RHA-NLS weremore » used for interaction with importin-{alpha}. Furthermore, the nuclear import of RHA-NLS was supported by importin-{alpha}1 and preferentially importin-{alpha}3. Our results indicate that the nuclear import of RHA is mediated by the importin-{alpha}3/importin-{beta}-dependent pathway and suggest that the specificity for importin may regulate the functions of cargo proteins.« less

iPS cells to model CDKL5-related disorders

PubMed Central

Amenduni, Mariangela; De Filippis, Roberta; Cheung, Aaron Y L; Disciglio, Vittoria; Epistolato, Maria Carmela; Ariani, Francesca; Mari, Francesca; Mencarelli, Maria Antonietta; Hayek, Youssef; Renieri, Alessandra; Ellis, James; Meloni, Ilaria

2011-01-01

Rett syndrome (RTT) is a progressive neurologic disorder representing one of the most common causes of mental retardation in females. To date mutations in three genes have been associated with this condition. Classic RTT is caused by mutations in the MECP2 gene, whereas variants can be due to mutations in either MECP2 or FOXG1 or CDKL5. Mutations in CDKL5 have been identified both in females with the early onset seizure variant of RTT and in males with X-linked epileptic encephalopathy. CDKL5 is a kinase protein highly expressed in neurons, but its exact function inside the cell is unknown. To address this issue we established a human cellular model for CDKL5-related disease using the recently developed technology of induced pluripotent stem cells (iPSCs). iPSCs can be expanded indefinitely and differentiated in vitro into many different cell types, including neurons. These features make them the ideal tool to study disease mechanisms directly on the primarily affected neuronal cells. We derived iPSCs from fibroblasts of one female with p.Q347X and one male with p.T288I mutation, affected by early onset seizure variant and X-linked epileptic encephalopathy, respectively. We demonstrated that female CDKL5-mutated iPSCs maintain X-chromosome inactivation and clones express either the mutant CDKL5 allele or the wild-type allele that serve as an ideal experimental control. Array CGH indicates normal isogenic molecular karyotypes without detection of de novo CNVs in the CDKL5-mutated iPSCs. Furthermore, the iPS cells can be differentiated into neurons and are thus suitable to model disease pathogenesis in vitro. PMID:21750574

iPS cells to model CDKL5-related disorders.

PubMed

Amenduni, Mariangela; De Filippis, Roberta; Cheung, Aaron Y L; Disciglio, Vittoria; Epistolato, Maria Carmela; Ariani, Francesca; Mari, Francesca; Mencarelli, Maria Antonietta; Hayek, Youssef; Renieri, Alessandra; Ellis, James; Meloni, Ilaria

2011-12-01

Rett syndrome (RTT) is a progressive neurologic disorder representing one of the most common causes of mental retardation in females. To date mutations in three genes have been associated with this condition. Classic RTT is caused by mutations in the MECP2 gene, whereas variants can be due to mutations in either MECP2 or FOXG1 or CDKL5. Mutations in CDKL5 have been identified both in females with the early onset seizure variant of RTT and in males with X-linked epileptic encephalopathy. CDKL5 is a kinase protein highly expressed in neurons, but its exact function inside the cell is unknown. To address this issue we established a human cellular model for CDKL5-related disease using the recently developed technology of induced pluripotent stem cells (iPSCs). iPSCs can be expanded indefinitely and differentiated in vitro into many different cell types, including neurons. These features make them the ideal tool to study disease mechanisms directly on the primarily affected neuronal cells. We derived iPSCs from fibroblasts of one female with p.Q347X and one male with p.T288I mutation, affected by early onset seizure variant and X-linked epileptic encephalopathy, respectively. We demonstrated that female CDKL5-mutated iPSCs maintain X-chromosome inactivation and clones express either the mutant CDKL5 allele or the wild-type allele that serve as an ideal experimental control. Array CGH indicates normal isogenic molecular karyotypes without detection of de novo CNVs in the CDKL5-mutated iPSCs. Furthermore, the iPS cells can be differentiated into neurons and are thus suitable to model disease pathogenesis in vitro.

The alpha-galactosidase A p.Arg118Cys variant does not cause a Fabry disease phenotype: data from individual patients and family studies.

PubMed

Ferreira, Susana; Ortiz, Alberto; Germain, Dominique P; Viana-Baptista, Miguel; Caldeira-Gomes, António; Camprecios, Marta; Fenollar-Cortés, Maria; Gallegos-Villalobos, Ángel; Garcia, Diego; García-Robles, José Antonio; Egido, Jesús; Gutiérrez-Rivas, Eduardo; Herrero, José Antonio; Mas, Sebastián; Oancea, Raluca; Péres, Paloma; Salazar-Martín, Luis Manuel; Solera-Garcia, Jesús; Alves, Helena; Garman, Scott C; Oliveira, João Paulo

2015-02-01

Lysosomal α-galactosidase A (α-Gal) is the enzyme deficient in Fabry disease (FD), an X-linked glycosphingolipidosis caused by pathogenic mutations affecting the GLA gene. The early-onset, multi-systemic FD classical phenotype is associated with absent or severe enzyme deficiency, as measured by in vitro assays, but patients with higher levels of residual α-Gal activity may have later-onset, more organ-restricted clinical presentations. A change in the codon 118 of the wild-type α-Gal sequence, replacing basic arginine by a potentially sulfhydryl-binding cysteine residue - GLA p.(Arg118Cys) -, has been recurrently described in large FD screening studies of high-risk patients. Although the Cys118 allele is associated with high residual α-Gal activity in vitro, it has been classified as a pathogenic mutation, mainly on the basis of theoretical arguments about the chemistry of the cysteine residue. However its pathogenicity has never been convincingly demonstrated by pathology criteria. We reviewed the clinical, biochemical and histopathology data obtained from 22 individuals of Portuguese and Spanish ancestry carrying the Cys118 allele, including 3 homozygous females. Cases were identified either on the differential diagnosis of possible FD manifestations and on case-finding studies (n=11; 4 males), or on unbiased cascade screening of probands' close relatives (n=11; 3 males). Overall, those data strongly suggest that the GLA p.(Arg118Cys) variant does not segregate with FD clinical phenotypes in a Mendelian fashion, but might be a modulator of the multifactorial risk of cerebrovascular disease. The Cys118 allelic frequency in healthy Portuguese adults (n=696) has been estimated as 0.001, therefore not qualifying for "rare" condition. Copyright © 2014 Elsevier Inc. All rights reserved.

Amino acid digestibility of different rye genotypes in caecectomised laying hens.

PubMed

Zuber, Tobias; Miedaner, Thomas; Rosenfelder, Pia; Rodehutscord, Markus

2016-12-01

This study investigated the variability of amino acid (AA) digestibility of rye grains in laying hens. Relationships between AA digestibility and physical properties (thousand seed weight, test weight, falling number, and extract viscoelasticity), chemical composition (proximate nutrients, non-starch polysaccharides, AA, minerals, and inositol phosphates), gross energy concentration, and in vitro solubility of nitrogen (N) of the grains were also examined. Twenty rye genotypes were grown under standardised agronomic and environmental conditions as part of a collaborative research project known as "GrainUp". Each genotype was added to a basal diet at 500 g/kg at the expense of maize starch to produce 20 rye diets. The experimental design comprised four Latin Squares (6 × 6) distributed over two runs, resulting in 12 experimental periods. Caecectomised laying hens (LSL-Classic) were individually kept in metabolism cages. Excreta were collected quantitatively for 4 d, and AA digestibility of the rye genotypes was determined using a regression approach. The digestibility of AA was generally low but varied significantly among the 20 rye genotypes, especially for Lys (digestibility range 35-59%), Met (57-75%), Thr (34-54%), and Trp (36-71%). Nevertheless, physical and chemical characteristics as well as the in vitro solubility of N correlated in only a few cases with AA digestibility. Multiple linear regression was used to calculate equations to predict AA digestibility based on the analysed characteristics. However, their explanatory power, as judged by the adjusted R(2), was not sufficiently precise for practical application (below 0.6 for most AA). In conclusion, the AA digestibility of rye grain is generally low and varies significantly between crop genotypes. Equations based on its physical and chemical characteristics are not sufficiently precise to be useful for feed formulation.

Recombinant rabbit leukemia inhibitory factor and rabbit embryonic fibroblasts support the derivation and maintenance of rabbit embryonic stem cells.

PubMed

Xue, Fei; Ma, Yinghong; Chen, Y Eugene; Zhang, Jifeng; Lin, Tzu-An; Chen, Chien-Hong; Lin, Wei-Wen; Roach, Marsha; Ju, Jyh-Cherng; Yang, Lan; Du, Fuliang; Xu, Jie

2012-08-01

The rabbit is a classical experimental animal species. A major limitation in using rabbits for biomedical research is the lack of germ-line-competent rabbit embryonic stem cells (rbESCs). We hypothesized that the use of homologous feeder cells and recombinant rabbit leukemia inhibitory factor (rbLIF) might improve the chance in deriving germ-line-competent rbES cells. In the present study, we established rabbit embryonic fibroblast (REF) feeder layers and synthesized recombinant rbLIF. We derived a total of seven putative rbESC lines, of which two lines (M5 and M23) were from culture Condition I using mouse embryonic fibroblasts (MEFs) as feeders supplemented with human LIF (hLIF) (MEF+hLIF). Another five lines (R4, R9, R15, R21, and R31) were derived from Condition II using REFs as feeder cells supplemented with rbLIF (REF+rbLIF). Similar derivation efficiency was observed between these two conditions (8.7% vs. 10.2%). In a separate experiment with 2×3 factorial design, we examined the effects of feeder cells (MEF vs. REF) and LIFs (mLIF, hLIF vs. rbLIF) on rbESC culture. Both Conditions I and II supported satisfactory rbESC culture, with similar or better population doubling time and colony-forming efficiency than other combinations of feeder cells with LIFs. Rabbit ESCs derived and maintained on both conditions displayed typical ESC characteristics, including ESC pluripotency marker expression (AP, Oct4, Sox2, Nanog, and SSEA4) and gene expression (Oct4, Sox2, Nanog, c-Myc, Klf4, and Dppa5), and the capacity to differentiate into three primary germ layers in vitro. The present work is the first attempt to establish rbESC lines using homologous feeder cells and recombinant rbLIF, by which the rbESCs were derived and maintained normally. These cell lines are unique resources and may facilitate the derivation of germ-line-competent rbESCs.

Classical Field Theory and the Stress-Energy Tensor

NASA Astrophysics Data System (ADS)

Swanson, Mark S.

2015-09-01

This book is a concise introduction to the key concepts of classical field theory for beginning graduate students and advanced undergraduate students who wish to study the unifying structures and physical insights provided by classical field theory without dealing with the additional complication of quantization. In that regard, there are many important aspects of field theory that can be understood without quantizing the fields. These include the action formulation, Galilean and relativistic invariance, traveling and standing waves, spin angular momentum, gauge invariance, subsidiary conditions, fluctuations, spinor and vector fields, conservation laws and symmetries, and the Higgs mechanism, all of which are often treated briefly in a course on quantum field theory. The variational form of classical mechanics and continuum field theory are both developed in the time-honored graduate level text by Goldstein et al (2001). An introduction to classical field theory from a somewhat different perspective is available in Soper (2008). Basic classical field theory is often treated in books on quantum field theory. Two excellent texts where this is done are Greiner and Reinhardt (1996) and Peskin and Schroeder (1995). Green's function techniques are presented in Arfken et al (2013).

In vitro culture of coconut (Cocos nucifera L.) zygotic embryos.

PubMed

Engelmann, Florent; Malaurie, Bernard; N'Nan, Oulo

2011-01-01

Coconut is a very important crop for millions of people in tropical countries. With coconut, in vitro culture protocols have been developed with two main objectives, viz. the large scale production of particular types of coconuts and the international exchange and conservation of coconut germplasm. The methods described in this chapter have been developed in the framework of collaborative activities between research institutes in Côte d'Ivoire and France. Two coconut embryo in vitro collecting protocols have been established, one consisting of storing the disinfected embryos in a KCl solution until they are brought back to the laboratory, where they are re-disinfected and inoculated in vitro under sterile conditions, and the other including in vitro inoculation of the embryos in the field. For international germplasm exchange, zygotic embryos inoculated in vitro in plastic test tubes or endosperm cylinders containing embryos in plastic bags are used. For in vitro culture, embryos are inoculated on semi-solid medium supplemented with sucrose and activated charcoal and placed in the dark, and then transferred to light conditions with the same (solid or liquid) medium once the first true leaf is visible and the root system has started developing.

Liquid jet breakup regimes at supercritical pressures

DOE PAGES

Oefelein, Joseph C.; Dahms, Rainer Norbert Uwe

2015-07-23

Previously, a theory has been presented that explains how discrete vapor–liquid interfaces become diminished at certain high-pressure conditions in a manner that leads to well known qualitative trends observed from imaging in a variety of experiments. Rather than surface tension forces, transport processes can dominate over relevant ranges of conditions. In this paper, this framework is now generalized to treat a wide range of fuel-oxidizer combinations in a manner consistent with theories of capillary flows and extended corresponding states theory. Different flow conditions and species-specific molecular properties are shown to produce distinct variations of interfacial structures and local free molecularmore » paths. These variations are shown to occur over the operating ranges in a variety of propulsion and power systems. Despite these variations, the generalized analysis reveals that the envelope of flow conditions at which the transition from classical sprays to diffusion-dominated mixing occurs exhibits a characteristic shape for all liquid–gas combinations. As a result, for alkane-oxidizer mixtures, it explains that these conditions shift to higher pressure flow conditions with increasing carbon number and demonstrates that, instead of widely assumed classical spray atomization, diffusion-dominated mixing may occur under relevant high-pressure conditions in many modern devices.« less

Eyeblink Conditioning: A Non-Invasive Biomarker for Neurodevelopmental Disorders

ERIC Educational Resources Information Center

Reeb-Sutherland, Bethany C.; Fox, Nathan A.

2015-01-01

Eyeblink conditioning (EBC) is a classical conditioning paradigm typically used to study the underlying neural processes of learning and memory. EBC has a well-defined neural circuitry, is non-invasive, and can be employed in human infants shortly after birth making it an ideal tool to use in both developing and special populations. In addition,…

Computational modeling and experimental validation of odor detection behaviours of classically conditioned parasitic wasp, Microplitis croceipes.

USDA-ARS?s Scientific Manuscript database

To further improve the sensitivity of odor¬ and odor concentration detection of the Wasp Hound, searching behaviors of a food-conditioned wasp in a confined area with the conditioning odor were recorded. The experiments were recorded using a video camera. First, the wasps are individually hand condi...

Metabolomics in Toxicology and Preclinical Research

PubMed Central

Ramirez, Tzutzuy; Daneshian, Mardas; Kamp, Hennicke; Bois, Frederic Y.; Clench, Malcolm R.; Coen, Muireann; Donley, Beth; Fischer, Steven M.; Ekman, Drew R.; Fabian, Eric; Guillou, Claude; Heuer, Joachim; Hogberg, Helena T.; Jungnickel, Harald; Keun, Hector C.; Krennrich, Gerhard; Krupp, Eckart; Luch, Andreas; Noor, Fozia; Peter, Erik; Riefke, Bjoern; Seymour, Mark; Skinner, Nigel; Smirnova, Lena; Verheij, Elwin; Wagner, Silvia; Hartung, Thomas; van Ravenzwaay, Bennard; Leist, Marcel

2013-01-01

Summary Metabolomics, the comprehensive analysis of metabolites in a biological system, provides detailed information about the biochemical/physiological status of a biological system, and about the changes caused by chemicals. Metabolomics analysis is used in many fields, ranging from the analysis of the physiological status of genetically modified organisms in safety science to the evaluation of human health conditions. In toxicology, metabolomics is the -omics discipline that is most closely related to classical knowledge of disturbed biochemical pathways. It allows rapid identification of the potential targets of a hazardous compound. It can give information on target organs and often can help to improve our understanding regarding the mode-of-action of a given compound. Such insights aid the discovery of biomarkers that either indicate pathophysiological conditions or help the monitoring of the efficacy of drug therapies. The first toxicological applications of metabolomics were for mechanistic research, but different ways to use the technology in a regulatory context are being explored. Ideally, further progress in that direction will position the metabolomics approach to address the challenges of toxicology of the 21st century. To address these issues, scientists from academia, industry, and regulatory bodies came together in a workshop to discuss the current status of applied metabolomics and its potential in the safety assessment of compounds. We report here on the conclusions of three working groups addressing questions regarding 1) metabolomics for in vitro studies 2) the appropriate use of metabolomics in systems toxicology, and 3) use of metabolomics in a regulatory context. PMID:23665807

Adenylyl cyclase-associated protein-1/CAP1 as a biological target substrate of gelatinase B/MMP-9

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

Cauwe, Benedicte; Martens, Erik; Van den Steen, Philippe E.

2008-09-10

Matrix metalloproteinases (MMPs) are classically associated with the turnover of secreted structural and functional proteins. Although MMPs have been shown to process also a kaleidoscope of membrane-associated substrates, little is known about the processing of intracellular proteins by MMPs. Physiological and pathological cell apoptosis, necrosis and tumor lysis by chemotherapy, radiotherapy or immunological cytotoxicity, are examples of conditions in which an overload of intracellular proteins becomes accessible to the action of MMPs. We used a model system of dying human myelomonocytic cells to study the processing of intracellular protein substrates by gelatinase B/MMP-9 in vitro. Adenylyl cyclase-associated protein-1 or CAP1more » was identified as a novel and most efficient substrate of gelatinase B/MMP-9. The presence of CAP1 in the extracellular milieu in vivo was documented by analysis of urine of patients with systemic autoimmune diseases. Whereas no active MMP-9 could be detected in urines of healthy controls, all urine samples of patients with clinical parameters of renal failure contained activated MMP-9 and/or MMP-2. In addition, in some of these patients indications of CAP1 cleavage are observed, implying CAP1 degradation in vivo. The high turnover rate of CAP1 by MMP-9, comparable to that of gelatin as the natural extracellular substrate of this enzyme, may be critical to prevent pathological conditions associated with considerable cytolysis.« less

Discriminative evaluative conditioning in the long-term after severe accidental injury.

PubMed

Oe, Misari; Schumacher, Sonja; Schnyder, Ulrich; Mueller-Pfeiffer, Christoph; Wilhelm, Frank H; Kuelen, Eveline; Martin-Soelch, Chantal

2016-06-30

Impairments in classical fear conditioning and deficits in discriminative learning are observed in posttraumatic stress disorder (PTSD). However, it is unknown whether similar impairments can be found with types of discriminative learning other than classical conditioning, such as evaluative conditioning (EC), in which the valence of a stimulus can be transferred to other stimuli. In this study, we investigated whether EC is also influenced by traumatic experiences independently of presence of PTSD. We tested 14 accident survivors with remitted PTSD, 14 survivors without PTSD, and 16 non-trauma controls. We used behavioral measures, psychophysiological indicators, and subjective ratings for tasks. General effects of learning were observed across groups and conditioning/extinction. Trauma controls had slower reaction times (RTs) to the aversive conditioned stimulus compared to appetitive conditioned and neutral stimuli, as well as slower RTs and increased accuracy during conditioning than during extinction. Remitted PTSD participants showed opposite results, demonstrating decreased accuracy and slower RTs during conditioning as compared to during extinction. No discriminative effect was found in the non-trauma controls and the remitted PTSD participants. These results suggest that a traumatic experience influences EC, and that this influence differs between individuals who have and have not developed PTSD after traumatic exposure. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

A remark on the energy conditions for Hawking's area theorem

NASA Astrophysics Data System (ADS)

Lesourd, Martin

2018-06-01

Hawking's area theorem is a fundamental result in black hole theory that is universally associated with the null energy condition. That this condition can be weakened is illustrated by the formulation of a strengthened version of the theorem based on an energy condition that allows for violations of the null energy condition. With the semi-classical context in mind, some brief remarks pertaining to the suitability of the area theorem and its energy condition are made.

Conditioned Emotional Distress in Women Receiving Chemotherapy for Breast Cancer.

ERIC Educational Resources Information Center

Jacobsen, Paul B.; And Others

1995-01-01

Investigated whether women undergoing outpatient chemotherapy for breast cancer can develop classically conditioned emotional distress. Patients' responses to a distinctive stimulus were assessed in a location not associated with chemotherapy administration. Results supported hypothesis that pairing a distinctive stimulus with chemotherapy would…

Behavioral determination of stimulus pair discrimination of auditory acoustic and electrical stimuli using a classical conditioning and heart-rate approach.

PubMed

Morgan, Simeon J; Paolini, Antonio G

2012-06-06

Acute animal preparations have been used in research prospectively investigating electrode designs and stimulation techniques for integration into neural auditory prostheses, such as auditory brainstem implants and auditory midbrain implants. While acute experiments can give initial insight to the effectiveness of the implant, testing the chronically implanted and awake animals provides the advantage of examining the psychophysical properties of the sensations induced using implanted devices. Several techniques such as reward-based operant conditioning, conditioned avoidance, or classical fear conditioning have been used to provide behavioral confirmation of detection of a relevant stimulus attribute. Selection of a technique involves balancing aspects including time efficiency (often poor in reward-based approaches), the ability to test a plurality of stimulus attributes simultaneously (limited in conditioned avoidance), and measure reliability of repeated stimuli (a potential constraint when physiological measures are employed). Here, a classical fear conditioning behavioral method is presented which may be used to simultaneously test both detection of a stimulus, and discrimination between two stimuli. Heart-rate is used as a measure of fear response, which reduces or eliminates the requirement for time-consuming video coding for freeze behaviour or other such measures (although such measures could be included to provide convergent evidence). Animals were conditioned using these techniques in three 2-hour conditioning sessions, each providing 48 stimulus trials. Subsequent 48-trial testing sessions were then used to test for detection of each stimulus in presented pairs, and test discrimination between the member stimuli of each pair. This behavioral method is presented in the context of its utilisation in auditory prosthetic research. The implantation of electrocardiogram telemetry devices is shown. Subsequent implantation of brain electrodes into the Cochlear Nucleus, guided by the monitoring of neural responses to acoustic stimuli, and the fixation of the electrode into place for chronic use is likewise shown.

Anterior Cruciate Ligament Biomechanics During Robotic and Mechanical Simulations of Physiologic and Clinical Motion Tasks: A Systematic Review and Meta-Analysis

PubMed Central

Bates, Nathaniel A.; Myer, Gregory D.; Shearn, Jason T.; Hewett, Timothy E.

2014-01-01

Investigators use in vitro joint simulations to invasively study the biomechanical behaviors of the anterior cruciate ligament. The aims of these simulations are to replicate physiologic conditions, but multiple mechanisms can be used to drive in vitro motions, which may influence biomechanical outcomes. The objective of this review was to examine, summarize, and compare biomechanical evidence related to anterior cruciate ligament function from in vitro simulations of knee motion. A systematic review was conducted (2004 to 2013) in Scopus, PubMed/Medline, and SPORTDiscus to identify peer-reviewed studies that reported kinematic and kinetic outcomes from in vitro simulations of physiologic or clinical tasks at the knee. Inclusion criteria for relevant studies were articles published in English that reported on whole-ligament anterior cruciate ligament mechanics during the in vitro simulation of physiologic or clinical motions on cadaveric knees that were unaltered outside of the anterior-cruciate-ligament-intact, -deficient, and -reconstructed conditions. A meta-analysis was performed to synthesize biomechanical differences between the anterior-cruciate-ligament-intact and reconstructed conditions. 77 studies met our inclusion/exclusion criteria and were reviewed. Combined joint rotations have the greatest impact on anterior cruciate ligament loads, but the magnitude by which individual kinematic degrees of freedom contribute to ligament loading during in vitro simulations is technique-dependent. Biomechanical data collected in prospective, longitudinal studies corresponds better with robotic-manipulator simulations than mechanical-impact simulations. Robotic simulation indicated that the ability to restore intact anterior cruciate ligament mechanics with anterior cruciate ligament reconstructions was dependent on loading condition and degree of freedom examined. PMID:25547070

Objectivity in a Noisy Photonic Environment through Quantum State Information Broadcasting

NASA Astrophysics Data System (ADS)

Korbicz, J. K.; Horodecki, P.; Horodecki, R.

2014-03-01

Recently, the emergence of classical objectivity as a property of a quantum state has been explicitly derived for a small object embedded in a photonic environment in terms of a spectrum broadcast form—a specific classically correlated state, redundantly encoding information about the preferred states of the object in the environment. However, the environment was in a pure state and the fundamental problem was how generic and robust is the conclusion. Here, we prove that despite the initial environmental noise, the emergence of the broadcast structure still holds, leading to the perceived objectivity of the state of the object. We also show how this leads to a quantum Darwinism-type condition, reflecting the classicality of proliferated information in terms of a limit behavior of the mutual information. Quite surprisingly, we find "singular points" of the decoherence, which can be used to faithfully broadcast a specific classical message through the noisy environment.

Generic emergence of classical features in quantum Darwinism.

PubMed

Brandão, Fernando G S L; Piani, Marco; Horodecki, Paweł

2015-08-12

Quantum Darwinism posits that only specific information about a quantum system that is redundantly proliferated to many parts of its environment becomes accessible and objective, leading to the emergence of classical reality. However, it is not clear under what conditions this mechanism holds true. Here we prove that the emergence of classical features along the lines of quantum Darwinism is a general feature of any quantum dynamics: observers who acquire information indirectly through the environment have effective access at most to classical information about one and the same measurement of the quantum system. Our analysis does not rely on a strict conceptual splitting between a system-of-interest and its environment, and allows one to interpret any system as part of the environment of any other system. Finally, our approach leads to a full operational characterization of quantum discord in terms of local redistribution of correlations.

Generic emergence of classical features in quantum Darwinism

NASA Astrophysics Data System (ADS)

Brandão, Fernando G. S. L.; Piani, Marco; Horodecki, Paweł

2015-08-01

Quantum Darwinism posits that only specific information about a quantum system that is redundantly proliferated to many parts of its environment becomes accessible and objective, leading to the emergence of classical reality. However, it is not clear under what conditions this mechanism holds true. Here we prove that the emergence of classical features along the lines of quantum Darwinism is a general feature of any quantum dynamics: observers who acquire information indirectly through the environment have effective access at most to classical information about one and the same measurement of the quantum system. Our analysis does not rely on a strict conceptual splitting between a system-of-interest and its environment, and allows one to interpret any system as part of the environment of any other system. Finally, our approach leads to a full operational characterization of quantum discord in terms of local redistribution of correlations.

Quantum deformations of conformal algebras with mass-like deformation parameters

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

Frydryszak, Andrzej; Lukierski, Jerzy; Mozrzymas, Marek

1998-12-15

We recall the mathematical apparatus necessary for the quantum deformation of Lie algebras, namely the notions of coboundary Lie algebras, classical r-matrices, classical Yang-Baxter equations (CYBE), Froebenius algebras and parabolic subalgebras. Then we construct the quantum deformation of D=1, D=2 and D=3 conformal algebras, showing that this quantization introduce fundamental mass parameters. Finally we consider with more details the quantization of D=4 conformal algebra. We build three classes of sl(4,C) classical r-matrices, satisfying CYBE and depending respectively on 8, 10 and 12 generators of parabolic subalgebras. We show that only the 8-dimensional r-matrices allow to impose the D=4 conformal o(4,2){approx_equal}su(2,2)more » reality conditions. Weyl reflections and Dynkin diagram automorphisms for o(4,2) define the class of admissible bases for given classical r-matrices.« less

Information transport in classical statistical systems

NASA Astrophysics Data System (ADS)

Wetterich, C.

2018-02-01

For "static memory materials" the bulk properties depend on boundary conditions. Such materials can be realized by classical statistical systems which admit no unique equilibrium state. We describe the propagation of information from the boundary to the bulk by classical wave functions. The dependence of wave functions on the location of hypersurfaces in the bulk is governed by a linear evolution equation that can be viewed as a generalized Schrödinger equation. Classical wave functions obey the superposition principle, with local probabilities realized as bilinears of wave functions. For static memory materials the evolution within a subsector is unitary, as characteristic for the time evolution in quantum mechanics. The space-dependence in static memory materials can be used as an analogue representation of the time evolution in quantum mechanics - such materials are "quantum simulators". For example, an asymmetric Ising model on a Euclidean two-dimensional lattice represents the time evolution of free relativistic fermions in two-dimensional Minkowski space.

Tree-level correlations in the strong field regime

NASA Astrophysics Data System (ADS)

Gelis, François

2017-09-01

We consider the correlation function of an arbitrary number of local observables in quantum field theory, in situations where the field amplitude is large. Using a quasi-classical approximation (valid for a highly occupied initial mixed state, or for a coherent initial state if the classical dynamics has instabilities), we show that at tree level these correlations are dominated by fluctuations at the initial time. We obtain a general expression of the correlation functions in terms of the classical solution of the field equation of motion and its derivatives with respect to its initial conditions, that can be arranged graphically as the sum of labeled trees where the nodes are the individual observables, and the links are pairs of derivatives acting on them. For 3-point (and higher) correlation functions, there are additional tree-level terms beyond the quasi-classical approximation, generated by fluctuations in the bulk.

[The influence of classical back and neck massage on the functional state of the cardiovascular system and the frequency-time characteristics of its variability in the adolescents].

PubMed

Sibir'ianov, A R; Sergeeva, N V; Podzolko, T Iu

2013-01-01

The present study was designed to study the influence of classical back and neck massage on the functional state of the cardiovascular system and its regulation under conditions of short-term physical loading in the healthy adolescents. It was shown that a course of classical massage promoted the reduction of arterial pressure in all children and the heart rate frequency in the boys. This effect was apparent as a reaction of blood circulation to the dosed physical exercises manifested as a rise in the heart rate frequency and stroke volume. The effects of classical massage were shown to be mediated through the alteration of the levels and mechanisms of regulation of the blood circulatory system and the enhancement of humoral and metabolic segmental sympathetic influences associated with the adaptation to the impact of massage therapy.

Classical and quantum aspects of Yang-Baxter Wess-Zumino models

NASA Astrophysics Data System (ADS)

Demulder, Saskia; Driezen, Sibylle; Sevrin, Alexander; Thompson, Daniel C.

2018-03-01

We investigate the integrable Yang-Baxter deformation of the 2d Principal Chiral Model with a Wess-Zumino term. For arbitrary groups, the one-loop β-functions are calculated and display a surprising connection between classical and quantum physics: the classical integrability condition is necessary to prevent new couplings being generated by renormalisation. We show these theories admit an elegant realisation of Poisson-Lie T-duality acting as a simple inversion of coupling constants. The self-dual point corresponds to the Wess-Zumino-Witten model and is the IR fixed point under RG. We address the possibility of having supersymmetric extensions of these models showing that extended supersymmetry is not possible in general.

The application of network synthesis to repeating classical gamma-ray bursts

NASA Technical Reports Server (NTRS)

Hurley, K.; Kouveliotou, C.; Fishman, J.; Meegan, C.; Laros, J.; Klebesadel, R.

1995-01-01

It has been suggested that the Burst and Transient Source Experiment (BATSE) gamma-ray burst catalog contains several groups of bursts clustered in space or in space and time, which provide evidence that a substantial fraction of the classical gamma-ray burst sources repeat. Because many of the bursts in these groups are weak, they are not directly detected by the Ulysses GRB experiment. We apply the network synthesis method to these events to test the repeating burst hypothesis. Although we find no evidence for repeating sources, the method must be applied under more general conditions before reaching any definite conclusions about the existence of classical gamma-ray burst repeating sources.

Investigation of ZPE and temperature effects on the Eley-Rideal recombination of hydrogen atoms on graphene using a multidimensional graphene-H-H potential

NASA Astrophysics Data System (ADS)

Sizun, M.; Bachellerie, D.; Aguillon, F.; Sidis, V.

2010-09-01

We study the Eley-Rideal recombination of H atoms on graphene under the physical conditions of the interstellar medium. Effects of the ZPE motions of the chemisorbed H atom and of the graphene thermal motions are investigated. Classical molecular dynamics calculations undertaken with the multidimensional potential of Bachellerie et al. [Phys. Chem. Chem. Phys. 11 (2009) 2715] are reported. The ZPE effects are the strongest. The closer the collision energy is to the classical reaction threshold the more sizeable the effects. The quantum reaction cross section is also estimated below and above the classical threshold using a capture model.

The Lack of Chemical Equilibrium does not Preclude the Use of the Classical Nucleation Theory in Circumstellar Outflows

NASA Technical Reports Server (NTRS)

Paquette, John A.; Nuth, Joseph A., III

2011-01-01

Classical nucleation theory has been used in models of dust nucleation in circumstellar outflows around oxygen-rich asymptotic giant branch stars. One objection to the application of classical nucleation theory (CNT) to astrophysical systems of this sort is that an equilibrium distribution of clusters (assumed by CNT) is unlikely to exist in such conditions due to a low collision rate of condensable species. A model of silicate grain nucleation and growth was modified to evaluate the effect of a nucleation flux orders of magnitUde below the equilibrium value. The results show that a lack of chemical equilibrium has only a small effect on the ultimate grain distribution.

Simple universal models capture all classical spin physics.

PubMed

De las Cuevas, Gemma; Cubitt, Toby S

2016-03-11

Spin models are used in many studies of complex systems because they exhibit rich macroscopic behavior despite their microscopic simplicity. Here, we prove that all the physics of every classical spin model is reproduced in the low-energy sector of certain "universal models," with at most polynomial overhead. This holds for classical models with discrete or continuous degrees of freedom. We prove necessary and sufficient conditions for a spin model to be universal and show that one of the simplest and most widely studied spin models, the two-dimensional Ising model with fields, is universal. Our results may facilitate physical simulations of Hamiltonians with complex interactions. Copyright © 2016, American Association for the Advancement of Science.

The effect of the coupling between the top plate and the fingerboard on the acoustic power radiated by a classical guitar (L).

PubMed

García-Mayén, Héctor; Santillán, Arturo

2011-03-01

An experimental investigation on the coupling between the fingerboard and the top plate of a classical guitar at low frequencies is presented. The study was carried out using a finished top plate under fixed boundary conditions and a commercial guitar. Radiated sound power was determined in one-third octave bands up to the band of 1 kHz based on measurements of sound intensity. The results provide evidence that the way in which the fingerboard and top plate are coupled is not a relevant factor in the radiated acoustic power of the classical guitar in the studied frequency range. © 2011 Acoustical Society of America

Influence of mRNA and protein synthesis inhibitors on the long-term memory acquisition of classically conditioned earthworms.

PubMed

Watanabe, Hikaru; Takaya, Tomohiro; Shimoi, Toshinobu; Ogawa, Hiroto; Kitamura, Yoshiichiro; Oka, Kotaro

2005-03-01

We investigated the process of memory consolidation following classical conditioning of earthworms. Earthworms were conditioned in paired trials by a weak vibration as a conditioned stimulus (CS), and by light as an unconditioned stimulus (US). The occurrence of a shrinking response upon exposure to the CS increased steadily with the number of paired training trials. When the training procedure was changed by increasing the intertrial interval (ITI), it was found that only those worms trained with a 68 s ITI exhibited long-term memory retention for at least 24 h. The influence of mRNA synthesis inhibition by actinomycin-D or of protein synthesis by anisomycin on memory consolidation was also examined. Induction of the long-term memory was blocked when either of these two compounds was injected into the body cavity of the worm within 25 min of conditioning with the 68 s ITI. These results demonstrate that the long-term memory is dependent upon protein synthesis in response to the upregulation of new transcription messengers.

Novel Basic Protein, PfN23, Functions as Key Macromolecule during Nacre Formation*

PubMed Central

Fang, Dong; Pan, Cong; Lin, Huijuan; Lin, Ya; Zhang, Guiyou; Wang, Hongzhong; He, Maoxian; Xie, Liping; Zhang, Rongqing

2012-01-01

The fine microstructure of nacre (mother of pearl) illustrates the beauty of nature. Proteins found in nacre were believed to be “natural hands” that control nacre formation. In the classical view of nacre formation, nucleation of the main minerals, calcium carbonate, is induced on and by the acidic proteins in nacre. However, the basic proteins were not expected to be components of nacre. Here, we reported that a novel basic protein, PfN23, was a key accelerator in the control over crystal growth in nacre. The expression profile, in situ immunostaining, and in vitro immunodetection assays showed that PfN23 was localized within calcium carbonate crystals in the nacre. Knocking down the expression of PfN23 in adults via double-stranded RNA injection led to a disordered nacre surface in adults. Blocking the translation of PfN23 in embryos using morpholino oligomers led to the arrest of larval development. The in vitro crystallization assay showed that PfN23 increases the rate of calcium carbonate deposition and induced the formation of aragonite crystals with characteristics close to nacre. In addition, we constructed the peptides and truncations of different regions of this protein and found that the positively charged C-terminal region was a key region for the function of PfN23 Taken together, the basic protein PfN23 may be a key accelerator in the control of crystal growth in nacre. This provides a valuable balance to the classic view that acidic proteins control calcium carbonate deposition in nacre. PMID:22416139

S100A13-C2A binary complex structure-a key component in the acidic fibroblast growth factor for the non-classical pathway

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

Mohan, Sepuru K.; Rani, Sandhya G.; Kumar, Sriramoju M.

2009-03-13

Fibroblast growth factors (FGFs) are key regulators of cell proliferation, differentiation, tumor-induced angiogenesis and migration. FGFs are essential for early embryonic development, organ formation and angiogenesis. They play important roles in tumor formation, inflammation, wound healing and restenosis. The biological effects of FGFs are mediated through the activation of the four transmembrane phosphotyrosine kinase receptors (FGFRs) in the presence of heparin sulfate proteoglycans (HSPGs) and therefore require the release of FGFs into the extracellular space. However, FGF-1 lacks the signal peptide required for the releasing of these proteins through the classical endoplasmic reticulum (ER)-Golgi secretary pathway. Maciag et al. demonstratedmore » that FGF-1 is exported through a non-classical release pathway involving the formation of a specific multiprotein complex [M. Landriscina, R. Soldi, C. Bagala, I. Micucci, S. Bellum, F. Tarantini, I. Prudovsky, T. Maciag, S100A13 participates in the release of fibroblast growth factor 1 in response to heat shock in vitro, J. Biol. Chem. 276 (2001) 22544-22552; C.M. Carreira, T.M. LaVallee, F. Tarantini, A. Jackson, J.T. Lathrop, B. Hampton, W.H. Burgess, T. Maciag, S100A13 is involved in the regulation of fibroblast growth factor-1 and p40 synaptotagmin-1 release in vitro, J. Biol. Chem. 273 (1998) 22224-22231; T.M. LaValle, F. Tarantini, S. Gamble, C.M. Carreira, A. Jackson, T. Maciag, Synaptotagmin-1 is required for fibroblast growth factor-1 release, J. Biol. Chem. 273 (1998) 22217-22223; C. Bagala, V. Kolev, A. Mandinova, R. Soldi, C. Mouta, I. Graziani, I, Prudovsky, T. Maciag, The alternative translation of synaptotagmin 1 mediates the non-classical release of FGF1, Biochem. Biophys. Res. Commun. 310 (2003) 1041-1047]. The protein constituents of this complex include FGF-1, S100A13 (a Ca{sup 2+}-binding protein), and the p40 form of synaptotagmin 1 (Syt1). To understand the molecular events in the FGF-1 releasing pathway, we have studied the interactions of S100A13 with C2A by {sup 1}H-{sup 15}N HSQC titration and 3D-filtered NOESY experiments. We characterized the binary complex structure of S100A13-C2A by using a variety of multi-dimensional NMR experiments. This complex acts as a template for FGF-1 dimerization and multiprotein complex formation.« less

The in vitro impact of toothpaste extracts on cell viability.

PubMed

Cvikl, Barbara; Lussi, Adrian; Gruber, Reinhard

2015-06-01

Toothpastes contain three main components: detergents, abrasives, and fluoride. Detergents, particularly sodium lauryl sulfate, have been proposed as components that enable toothpastes to produce cytotoxic effects in vitro. However, not all toothpastes contain sodium lauryl sulfate, and almost no studies have found an association between detergents and the in vitro cytotoxicity of toothpastes. The present study examined the in vitro cytotoxicity of nine commercially available toothpastes containing four different detergents. Toothpastes were diluted in serum-free medium, centrifuged, and filter sterilized. The half-lethal concentration of the toothpaste-conditioned medium (TCM) was calculated based on the formation of formazan by gingival fibroblasts, oral squamous cell carcinoma HSC-2 cells, and L929 cells. Cell proliferation was analyzed, and live-dead staining was performed, after exposure of cells to conditioned medium prepared with 1% toothpaste (1% TCM). It was found that toothpastes containing sodium lauryl sulfate and amine fluoride strongly inhibited cell viability with the half-lethal concentration being obtained with conditioned medium prepared with approximately 1% toothpaste (1% TCM). Toothpastes containing cocamidopropyl betaine and Steareth-20 showed higher half-lethal concentration values, with the half-lethal concentration being obtained with conditioned medium prepared with 10% (10% TCM) and 70% (70% TCM) toothpaste, respectively. Proliferation and live-dead data were consistent with the cell-viability analyses. These results demonstrate that the type of detergent in toothpastes can be associated with changes in in vitro cell toxicity. © 2015 Eur J Oral Sci.

High glucose-induced Ca2+ overload and oxidative stress contribute to apoptosis of cardiac cells through mitochondrial dependent and independent pathways.

PubMed

Kumar, Sandeep; Kain, Vasundhara; Sitasawad, Sandhya L

2012-07-01

Cardiac cell apoptosis is the initiating factor of cardiac complications especially diabetic cardiomyopathy. Mitochondria are susceptible to the damaging effects of elevated glucose condition. Calcium overload and oxidative insult are the two mutually non-exclusive phenomena suggested to cause cardiac dysfunction. Here, we examined the effect of high-glucose induced calcium overload in calpain-1 mediated cardiac apoptosis in an in vitro setting. H9c2, rat ventricular myoblast cell line was treated with elevated glucose condition and the cellular consequences were studied. Intracellular calcium trafficking, ROS generation, calpain-1 activation and caspase-12 and caspase-9 pathway were studied using flow cytometry, confocal microscopy and Western blot analysis. High-glucose treatment resulted in increased intracellular calcium ([Ca2+]i) which was mobilized to the mitochondria. Concomitant intra-mitochondrial calcium ([Ca2+]m) increase resulted in enhanced reactive oxygen and nitrogen species generation. These events led to mitochondrial dysfunction and apoptosis. Cardiomyocyte death exhibited several classical markers of apoptosis, including activation of caspases, appearance of annexin V on the outer plasma membrane, increased population of cells with sub-G0/G1 DNA content and nuclear condensation. Key findings include elucidation of cell signaling mechanism of high-glucose induced calcium-dependent cysteine protease calpain-1 activation, which triggers non-conventional caspases as alternate mode of cell death. This information increases the understanding of cardiac cell death under hyperglycemic condition and can possibly be extended for designing new therapeutic strategies for diabetic cardiomyopathy. The novel findings of the study reveal that high glucose induces apoptosis by both mitochondria-dependent and independent pathways via concomitant rise in intracellular calcium. Copyright © 2012 Elsevier B.V. All rights reserved.

The neural underpinnings of music listening under different attention conditions.

PubMed

Jäncke, Lutz; Leipold, Simon; Burkhard, Anja

2018-05-02

Most studies examining the neural underpinnings of music listening have no specific instruction on how to process the presented musical pieces. In this study, we explicitly manipulated the participants' focus of attention while they listened to the musical pieces. We used an ecologically valid experimental setting by presenting the musical stimuli simultaneously with naturalistic film sequences. In one condition, the participants were instructed to focus their attention on the musical piece (attentive listening), whereas in the second condition, the participants directed their attention to the film sequence (passive listening). We used two instrumental musical pieces: an electronic pop song, which was a major hit at the time of testing, and a classical musical piece. During music presentation, we measured electroencephalographic oscillations and responses from the autonomic nervous system (heart rate and high-frequency heart rate variability). During passive listening to the pop song, we found strong event-related synchronizations in all analyzed frequency bands (theta, lower alpha, upper alpha, lower beta, and upper beta). The neurophysiological responses during attentive listening to the pop song were similar to those of the classical musical piece during both listening conditions. Thus, the focus of attention had a strong influence on the neurophysiological responses to the pop song, but not on the responses to the classical musical piece. The electroencephalographic responses during passive listening to the pop song are interpreted as a neurophysiological and psychological state typically observed when the participants are 'drawn into the music'.

Impaired eye-blink conditioning in waggler, a mutant mouse with cerebellar BDNF deficiency.

PubMed

Bao, S; Chen, L; Qiao, X; Knusel, B; Thompson, R F

1998-01-01

In addition to their trophic functions, neurotrophins are also implicated in synaptic modulation and learning and memory. Although gene knockout techniques have been used widely in studying the roles of neurotrophins at molecular and cellular levels, behavioral studies using neurotrophin knockouts are limited by the early-onset lethality and various sensory deficits associated with the gene knockout mice. In the present study, we found that in a spontaneous mutant mouse, waggler, the expression of brain-derived neurotrophic factor (BDNF) was selectively absent in the cerebellar granule cells. The cytoarchitecture of the waggler cerebellum appeared to be normal at the light microscope level. The mutant mice exhibited no sensory deficits to auditory stimuli or heat-induced pain. However, they were massively impaired in classic eye-blink conditioning. These results suggest that BDNF may have a role in normal cerebellar neuronal function, which, in turn, is essential for classic eye-blink conditioning.

Classic histamine H1 receptor antagonists: a critical review of their metabolic and pharmacokinetic fate from a bird's eye view.

PubMed

Sharma, A; Hamelin, B A

2003-04-01

The so-called "classic" histamine H(1) receptor antagonists are highly lipophilic compounds associated with significant biotransformation and tissue distribution. They are categorized according to their chemical structure into ethanolamines, alkylamines, ethylenediamines, piperazines, phenothiazines and piperidines, all of which have characteristic metabolic fates. The former four categories undergo primarily cytochrome P450-mediated oxidative N-desalkylations and deamination whereas the aromatic rings of the latter two undergo P450-mediated oxidative hydroxylation and/or epoxide formation. The common tertiary amino group is susceptible to oxidative metabolism by flavin containing monooxygenases forming N-oxides, and the alicyclic tertiary amines produce small amounts (up to 7%) of N-glucuronides in humans. Species, sex and racial differences in the metabolism and pharmacokinetics of antihistamines are known. Specific P450-isozymes implicated in the metabolism were identified in a few cases, such as CYP2D6 that contributes to the metabolism of promethazine, diphenhydramine and chlorpheniramine. Low circulating plasma concentrations of antihistamines are in part explained by significant first-pass effect and tissue distribution. Antihistaminic effects last up to 6 hours though some compounds exhibit a longer duration of action due to circulating active metabolites. Importantly, diphenhydramine inhibited CYP2D6 leading to a clinically significant drug-drug interaction with metoprolol. Other classic antihistamines were shown to be potent in vitro inhibitors of CYP2D6 and CYP3A4. The prescription-free access to most classic antihistamines can easily lead to their co-administration with other drugs metabolized by the same enzyme system thereby leading to drug accumulation and adverse effects. In depth knowledge of the metabolic pathways of classic antihistamines and the enzymes involved is crucial to prevent the high incidence of drug interactions in humans, which are predictable based on pre-clinical data but unexpected when such data is unavailable.

Carboxypeptidase-M is regulated by lipids and CSFs in macrophages and dendritic cells and expressed selectively in tissue granulomas and foam cells

PubMed Central

Tsakiris, Ioannis; Torocsik, Daniel; Gyongyosi, Adrienn; Dozsa, Aniko; Szatmari, Istvan; Szanto, Attila; Soos, Gyorgyike; Nemes, Zoltan; Igali, Laszlo; Marton, Ildiko; Takats, Zoltan; Nagy, Laszlo; Dezso, Balazs

2012-01-01

Granulomatous inflammations, characterized by the presence of activated macrophages (MAs) forming epithelioid cell (EPC) clusters, are usually easy to recognize. However, in ambiguous cases the use of a MA marker that expresses selectively in EPCs may be needed. Here, we report that carboxypeptidase-M (CPM), a MA-differentiation marker, is preferentially induced in EPCs of all granuloma types studied, but not in resting MAs. As CPM is not expressed constitutively in MAs, this allows utilization of CPM-immunohistochemistry in diagnostics of minute granuloma detection when dense non-granulomatous MAs are also present. Despite this rule, hardly any detectable CPM was found in advanced/active tubercle caseous disease, albeit in early tuberculosis granuloma, MAs still expressed CPM. Indeed, in vitro both the CPM-protein and -mRNA became downregulated when MAs were infected with live mycobacteria. In vitro, MA-CPM transcript is neither induced remarkably by interferon-γ, known to cause classical MA activation, nor by IL-4, an alternative MA activator. Instead, CPM is selectively expressed in lipid-laden MAs, including the foam cells of atherosclerotic plaques, xanthomatous lesions and lipid pneumonias. By using serum, rich in lipids, and low-density lipoprotein (LDL) or VLDL, CPM upregulation could be reproduced in vitro in monocyte-derived MAs both at transcriptional and protein levels, and the increase is repressed under lipid-depleted conditions. The microarray analyses support the notion that CPM induction correlates with a robust progressive increase in CPM gene expression during monocyte to MA maturation and dendritic cell (DC) differentiation mediated by granulocyte–MA-colony-stimulating factor+IL-4. M-CSF alone also induced CPM. These results collectively indicate that CPM upregulation in MAs is preferentially associated with increased lipid uptake, and exposure to CSF, features of EPCs, also. Therefore, CPM-immunohistochemistry is useful for granuloma and foam MA detections in tissue sections. Furthermore, the present data offer CPM for the first time to be a novel marker and cellular player in lipid uptake and/or metabolism of MAs by promoting foam cell formation. PMID:22157720

In vivo and in vitro testing for selenium and selenium compounds bioavailability assessment in foodstuff.

PubMed

Moreda-Piñeiro, Jorge; Moreda-Piñeiro, Antonio; Bermejo-Barrera, Pilar

2017-03-04

The assessment of selenium and selenium species bioavailability in foodstuff is of special concern on the context of human nutrition. In vivo (human and animal), and in vitro tests are important approaches for estimating the bioavailability of toxic and essential compounds to humans. An overview on in vivo and in vitro bioavailability assays for releasing selenium and selenium species in foodstuffs is summarized. Se and Se species content in a foodstuff critically influence Se bioavailability and bioactivity to humans and animals. Se bioavailability is affected by foodstuff-matrix major composition and minor components. Foodstuffs processing and/or treatments could enhancement or decrease Se bioavailability. Experimental conditions such as the selection of healthy status of examined people (in in vivo humans approaches), the selection of animal model (in vivo animals approaches), or the selection of GI conditions (in in vitro tests) could determines the results. Thus, international standardized protocol for in vivo and in vitro approaches assessment is mandatory.

Yellow fever: ecology, epidemiology, and role in the collapse of the Classic lowland Maya civilization.

PubMed

Wilkinson, R L

1995-07-01

Mystery has long surrounded the collapse of the Classic lowland Mayan civilization of the Peten region in Guatemala. Recent population reconstructions derived from archaeological evidence from the central lowlands show population declines from urban levels of between 2.5 and 3.5 million to around 536,000 in the two hundred year interval between 800 A.D. and 1000 A.D., the period known as the Classic Maya Collapse. A steady, but lesser rate of population decline continued until the time of European contact. When knowledge of the ecology and epidemiology of yellow fever and its known mosquito vectors are compared with what is known of the ecological conditions of lowland Guatemala as modified by the Classic Maya, provocative similarities are observed. When infection and mortality patterns of more recent urban yellow fever epidemics are used as models for a possible series of Classic Maya epidemics, a correlation is noted between the modeled rate of population decline for a series of epidemics, and population decline figures reconstructed from archaeological evidence.

Duration of the unconditioned stimulus in appetitive conditioning of honeybees differentially impacts learning, long-term memory strength, and the underlying protein synthesis

PubMed Central

Marter, Kathrin; Grauel, M. Katharina; Lewa, Carmen; Morgenstern, Laura; Buckemüller, Christina; Heufelder, Karin; Ganz, Marion

2014-01-01

This study examines the role of stimulus duration in learning and memory formation of honeybees (Apis mellifera). In classical appetitive conditioning honeybees learn the association between an initially neutral, conditioned stimulus (CS) and the occurrence of a meaningful stimulus, the unconditioned stimulus (US). Thereby the CS becomes a predictor for the US eliciting a conditioned response (CR). Here we study the role of US duration in classical conditioning by examining honeybees conditioned with different US durations. We quantify the CR during acquisition, memory retention, and extinction of the early long-term memory (eLTM), and examine the molecular mechanisms of eLTM by interfering with protein synthesis. We find that the US duration affects neither the probability nor the strength of the CR during acquisition, eLTM retention, and extinction 24 h after conditioning. However, we find that the resistance to extinction 24 h after conditioning is susceptible to protein synthesis inhibition depending on the US duration. We conclude that the US duration does not affect the predictability of the US but modulates the protein synthesis underlying the eLTM's strength. Thus, the US duration differentially impacts learning, eLTM strength, and its underlying protein synthesis. PMID:25403456

A Compilation of In Vitro Rate and Affinity Values for Xenobiotic Biotransformation in Fish, Measured Under Physiological Conditions

EPA Science Inventory

This manuscript presents a summary of in vitro rate and affinity data for xenobiotic biotransformation enzymes in fish...One potential use of this data summary is to support in vitro to in vivo metabolism extrapolations which can be used as inputs to chemical kinetic models for f...

Analysis and Synthesis of Adaptive Neural Elements and Assembles

DTIC Science & Technology

1993-09-30

of an Aplysia sensory neuron was developed that reflects the subcellular processes underlying activity-dependent neuromodulation . This single- Page -3... neuromodulation learning rule could simulate some higher-order features of classical conditioning, such second-order conditioning and blocking. During the...reporting period, simulations were used to test the hypothesis that activity-dependent neuromodulation could also support operant conditioning. A

Duration of the Unconditioned Stimulus in Appetitive Conditioning of Honeybees Differentially Impacts Learning, Long-Term Memory Strength, and the Underlying Protein Synthesis

ERIC Educational Resources Information Center

Marter, Kathrin; Grauel, M. Katharina; Lewa, Carmen; Morgenstern, Laura; Buckemüller, Christina; Heufelder, Karin; Ganz, Marion; Eisenhardt, Dorothea

2014-01-01

This study examines the role of stimulus duration in learning and memory formation of honeybees ("Apis mellifera"). In classical appetitive conditioning honeybees learn the association between an initially neutral, conditioned stimulus (CS) and the occurrence of a meaningful stimulus, the unconditioned stimulus (US). Thereby the CS…

Learning-Dependent Potentiation in the Vibrissal Motor Cortex Is Closely Related to the Acquisition of Conditioned Whisker Responses in Behaving Mice

ERIC Educational Resources Information Center

Delgado-Garcia, Jose Maria; Troncoso, Julieta; Munera, Alejandro

2007-01-01

The role of the primary motor cortex in the acquisition of new motor skills was evaluated during classical conditioning of vibrissal protraction responses in behaving mice, using a trace paradigm. Conditioned stimulus (CS) presentation elicited a characteristic field potential in the vibrissal motor cortex, which was dependent on the synchronized…

An increase in IL-1β concentrations in embryo culture-conditioned media obtained by in vitro fertilization on day 3 is related to successful implantation.

PubMed

Sequeira, Karina; Espejel-Núñez, Aurora; Vega-Hernández, Eva; Molina-Hernández, Anayansi; Grether-González, Patricia

2015-11-01

This study aimed to evaluate interleukin (IL)-1β concentrations in maternal serum and in embryo-cultured conditioned media and to correlate these findings with success of implantation. A total of 70 infertile women who underwent in vitro fertilization treatment were studied. IL-1β concentrations were quantified in maternal serum and in embryo culture-conditioned media on days 1 and 3. The findings were compared between those who achieved pregnancy and those who did not. No significant differences were found in IL-1β serum concentrations between the groups. IL-1β was not detected in day 1 culture-conditioned medium. On day 3, IL-1β was quantified in 27 patients, and IL-1β concentrations were significantly higher in women who achieved pregnancy than in those who did not (p < 0.001). High IL-1β concentrations in day 3 culture-conditioned medium in patients who achieve pregnancy after in vitro fertilization treatment indicate a possible role of embryonic IL-1β in the implantation process.

Classical and numerical approaches to determining V-section band clamp axial stiffness

NASA Astrophysics Data System (ADS)

Barrans, Simon M.; Khodabakhshi, Goodarz; Muller, Matthias

2015-01-01

V-band clamp joints are used in a wide range of applications to connect circular flanges, for ducts, pipes and the turbocharger housing. Previous studies and research on V-bands are either purely empirical or analytical with limited applicability on the variety of V-band design and working conditions. In this paper models of the V-band are developed based on the classical theory of solid mechanics and the finite element method to study the behaviour of theV-bands under axial loading conditions. The good agreement between results from the developed FEA and the classical model support the suitability of the latter to modelV-band joints with diameters greater than 110mm under axial loading. The results from both models suggest that the axial stiffness for thisV-band cross section reaches a peak value for V-bands with radius of approximately 150 mmacross a wide range of coefficients of friction. Also, it is shown that the coefficient of friction and the wedge angle have a significant effect on the axial stiffness of V-bands.

Stimulus- and response-reinforcer contingencies in autoshaping, operant, classical, and omission training procedures in rats.

PubMed

Atnip, G W

1977-07-01

Separate groups of rats received 500 trials of lever-press training under autoshaping (food delivery followed 10-second lever presentations, or occurred immediately following a response); operant conditioning (responding was necessary for food delivery); and classical conditioning (food followed lever presentations regardless of responding). Each group then received 500 trials on an omission procedure in which food was omitted on trials with a response. Another group received 1000 trials on the omission procedure, and a fifth group, random control, received 1000 uncorrelated presentations of lever and food. The autoshaping, operant, and classical groups reached high response levels by the end of initial training. Acquisition was fastest in the autoshaping group. Responding remained consistently low in the control group. The omission group responded at a level between the control group and the other three groups. During omission training, responding in these three groups declined to the omission-group level. During omission training, the rats continued contacting the lever frequently after lever pressing had declined. Response maintenance under omission training seems not to require topographic similarity between the response and reinforcer-elicited consummatory behaviors.

Stimulus- and response-reinforcer contingencies in autoshaping, operant, classical, and omission training procedures in rats

PubMed Central

Atnip, Gilbert W.

1977-01-01

Separate groups of rats received 500 trials of lever-press training under autoshaping (food delivery followed 10-second lever presentations, or occurred immediately following a response); operant conditioning (responding was necessary for food delivery); and classical conditioning (food followed lever presentations regardless of responding). Each group then received 500 trials on an omission procedure in which food was omitted on trials with a response. Another group received 1000 trials on the omission procedure, and a fifth group, random control, received 1000 uncorrelated presentations of lever and food. The autoshaping, operant, and classical groups reached high response levels by the end of initial training. Acquisition was fastest in the autoshaping group. Responding remained consistently low in the control group. The omission group responded at a level between the control group and the other three groups. During omission training, responding in these three groups declined to the omission-group level. During omission training, the rats continued contacting the lever frequently after lever pressing had declined. Response maintenance under omission training seems not to require topographic similarity between the response and reinforcer-elicited consummatory behaviors. PMID:16812014

High-Order Accurate Solutions to the Helmholtz Equation in the Presence of Boundary Singularities

DTIC Science & Technology

2015-03-31

FD scheme is only consistent for classical solutions of the PDE . For this reason, we implement the method of singularity subtraction as a means for...regularity due to the boundary conditions. This is because the FD scheme is only consistent for classical solutions of the PDE . For this reason, we...Introduction In the present work, we develop a high-order numerical method for solving linear elliptic PDEs with well-behaved variable coefficients on

Stochastic inflation in phase space: is slow roll a stochastic attractor?

NASA Astrophysics Data System (ADS)

Grain, Julien; Vennin, Vincent

2017-05-01

An appealing feature of inflationary cosmology is the presence of a phase-space attractor, ``slow roll'', which washes out the dependence on initial field velocities. We investigate the robustness of this property under backreaction from quantum fluctuations using the stochastic inflation formalism in the phase-space approach. A Hamiltonian formulation of stochastic inflation is presented, where it is shown that the coarse-graining procedure—where wavelengths smaller than the Hubble radius are integrated out—preserves the canonical structure of free fields. This means that different sets of canonical variables give rise to the same probability distribution which clarifies the literature with respect to this issue. The role played by the quantum-to-classical transition is also analysed and is shown to constrain the coarse-graining scale. In the case of free fields, we find that quantum diffusion is aligned in phase space with the slow-roll direction. This implies that the classical slow-roll attractor is immune to stochastic effects and thus generalises to a stochastic attractor regardless of initial conditions, with a relaxation time at least as short as in the classical system. For non-test fields or for test fields with non-linear self interactions however, quantum diffusion and the classical slow-roll flow are misaligned. We derive a condition on the coarse-graining scale so that observational corrections from this misalignment are negligible at leading order in slow roll.

Changes in water quality along the course of a river - Classic monitoring versus patrol monitoring

NASA Astrophysics Data System (ADS)

Absalon, Damian; Kryszczuk, Paweł; Rutkiewicz, Paweł

2017-11-01

Monitoring of water quality is a tool necessary to assess the condition of waterbodies in order to properly formulate water management plans. The paper presents the results of patrol monitoring of a 40-kilometre stretch of the Oder between Racibórz and Koźle. It has been established that patrol monitoring is a good tool for verifying the distribution of points of classic stationary monitoring, particularly in areas subject to varied human impact, where tributaries of the main river are very diversified as regards hydrochemistry. For this reason the results of operational monitoring carried out once every few years may not be reliable and the presented condition of the monitored waterbodies may be far from reality.

Single, Complete, Probability Spaces Consistent With EPR-Bohm-Bell Experimental Data

NASA Astrophysics Data System (ADS)

Avis, David; Fischer, Paul; Hilbert, Astrid; Khrennikov, Andrei

2009-03-01

We show that paradoxical consequences of violations of Bell's inequality are induced by the use of an unsuitable probabilistic description for the EPR-Bohm-Bell experiment. The conventional description (due to Bell) is based on a combination of statistical data collected for different settings of polarization beam splitters (PBSs). In fact, such data consists of some conditional probabilities which only partially define a probability space. Ignoring this conditioning leads to apparent contradictions in the classical probabilistic model (due to Kolmogorov). We show how to make a completely consistent probabilistic model by taking into account the probabilities of selecting the settings of the PBSs. Our model matches both the experimental data and is consistent with classical probability theory.

Well-posedness for a class of doubly nonlinear stochastic PDEs of divergence type

NASA Astrophysics Data System (ADS)

Scarpa, Luca

2017-08-01

We prove well-posedness for doubly nonlinear parabolic stochastic partial differential equations of the form dXt - div γ (∇Xt) dt + β (Xt) dt ∋ B (t ,Xt) dWt, where γ and β are the two nonlinearities, assumed to be multivalued maximal monotone operators everywhere defined on Rd and R respectively, and W is a cylindrical Wiener process. Using variational techniques, suitable uniform estimates (both pathwise and in expectation) and some compactness results, well-posedness is proved under the classical Leray-Lions conditions on γ and with no restrictive smoothness or growth assumptions on β. The operator B is assumed to be Hilbert-Schmidt and to satisfy some classical Lipschitz conditions in the second variable.

Electrophysiological CNS-processes related to associative learning in humans.

PubMed

Christoffersen, Gert R J; Schachtman, Todd R

2016-01-01

The neurophysiology of human associative memory has been studied with electroencephalographic techniques since the 1930s. This research has revealed that different types of electrophysiological processes in the human brain can be modified by conditioning: sensory evoked potentials, sensory induced gamma-band activity, periods of frequency-specific waves (alpha and beta waves, the sensorimotor rhythm and the mu-rhythm) and slow cortical potentials. Conditioning of these processes has been studied in experiments that either use operant conditioning or repeated contingent pairings of conditioned and unconditioned stimuli (classical conditioning). In operant conditioning, the appearance of a specific brain process is paired with an external stimulus (neurofeedback) and the feedback enables subjects to obtain varying degrees of control of the CNS-process. Such acquired self-regulation of brain activity has found practical uses for instance in the amelioration of epileptic seizures, Autism Spectrum Disorders (ASD) and Attention Deficit Hyperactivity Disorder (ADHD). It has also provided communicative means of assistance for tetraplegic patients through the use of brain computer interfaces. Both extra and intracortically recorded signals have been coupled with contingent external feedback. It is the aim for this review to summarize essential results on all types of electromagnetic brain processes that have been modified by classical or operant conditioning. The results are organized according to type of conditioned EEG-process, type of conditioning, and sensory modalities of the conditioning stimuli. Copyright © 2015 Elsevier B.V. All rights reserved.

In vitro and in situ characterization of arthroscopic loop security and knot security of braided polyblend sutures: a biomechanical study.

PubMed

Armstrong, Lucas C; Chong, Alexander; Livermore, Ryan W; Prohaska, Daniel J; Doyon, Amanda N; Wooley, Paul H

2015-04-01

We conducted a study to evaluate biomechanical performance during destructive testing of several different suture materials in various arthroscopic knot configurations under both in vitro and in situ conditions. Surgeons of different levels of experience tied the knots. Three different arthroscopic knots (static surgeon's, Weston, Tennessee slider) with 3 reverse half-hitches on alternating posts were tested using Fiberwire, ForceFiber, Orthocord, and Ultrabraid suture materials under both in vitro and in situ (blood plasma at 37°C) conditions. Three surgeons of different experience levels tied the knots on a post 30 mm in circumference. A single load-to-failure test was performed. There were no significant in vitro-in situ differences for Ultrabraid in the different knot configurations or with the different experience levels. Surgeon B (intermediate experience) showed no significant differences between test conditions for any knot configuration or suture material. With Tennessee slider knots, surgeon C (least experience) showed significantly lower clinical failure load under both test conditions and had a higher percentage of complete knot slippage. Surgeon B had no knot slippage with use of Fiberwire. Both the aqueous environment and the surgeon's familiarity with certain knots have an effect on knot security.

Analogue of the Kelley condition for optimal systems with retarded control

NASA Astrophysics Data System (ADS)

Mardanov, Misir J.; Melikov, Telman K.

2017-07-01

In this paper, we consider an optimal control problem with retarded control and study a larger class of singular (in the classical sense) controls. The Kelley and equality type optimality conditions are obtained. To prove our main results, we use the Legendre polynomials as variations of control.

EYEBLINK CONDITIONING IN THE INFANT RAT: AN ANIMAL MODEL OF LEARNING IN DEVELOPMENTAL NEUROTOXICOLOGY

EPA Science Inventory

Classical conditioning of the eyeblink reflex is a relatively simple procedure for studying associative learning that was first developed for use with human subjects more than half a century ago. The use of this procedure in laboratory animals by psychologists and neuro-scientist...

Cerebellar Secretin Modulates Eyeblink Classical Conditioning

ERIC Educational Resources Information Center

Fuchs, Jason R.; Robinson, Gain M.; Dean, Aaron M.; Schoenberg, Heidi E.; Williams, Michael R.; Morielli, Anthony D.; Green, John T.

2014-01-01

We have previously shown that intracerebellar infusion of the neuropeptide secretin enhances the acquisition phase of eyeblink conditioning (EBC). Here, we sought to test whether endogenous secretin also regulates EBC and to test whether the effect of exogenous and endogenous secretin is specific to acquisition. In Experiment 1, rats received…

Short communication: effects of serum obtained from dairy cows with low or high body condition score on in vitro embryo development.

PubMed

Oba, M; Miyashita, S; Nishii, R; Koiwa, M; Koyama, H; Ambrose, D J; Dochi, O

2013-03-01

The objective of the study was to determine whether the serum obtained from animals differing in body condition score (BCS) affects in vitro embryo development. After in vitro fertilization, serum obtained from dairy cows of either low (L-BCS; 2.1 ± 0.14 on a scale of 1 to 5) or high BCS (H-BCS; 4.0 ± 0.0), or commercially available bovine serum (control) was added at 5% concentration to the in vitro culture medium. Use of serum obtained from H-BCS cows increased the cleavage rates compared with control serum at both 24 and 48 h after in vitro fertilization (78.3 vs. 71.9% and 79.9 vs. 75.1%, respectively), whereas use of serum obtained from L-BCS cows increased the blastocyst rate compared with control serum at 7d (23.8 vs. 19.1%), but this difference was not evident at 8 or 9 d after in vitro fertilization. As nonesterified fatty acid concentrations were highest in control serum, followed by serum from L-BCS and H-BCS cows (621, 559, and 272 μEq/L, respectively), a high concentration of nonesterified fatty acids might adversely affect the very early stages of embryo development, and its negative effects might be greater immediately after fertilization compared with developmental stages after morula formation. Our findings also indicate that factors promoting early stage embryo development do not necessarily promote blastocyst development. Serum obtained from animals under different physiological conditions may be used for in vitro embryo culture to study the effects of nutritional management of dairy cattle on embryo development. Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Spine micromorphology of normal and hyperhydric Mammillaria gracilis Pfeiff. (Cactaceae) shoots.

PubMed

Peharec, P; Posilović, H; Balen, B; Krsnik-Rasol, M

2010-07-01

Artificial conditions of tissue culture affect growth and physiology of crassulacean acid metabolism plants which often results in formation of hyperhydric shoots. In in vitro conditions Mammillaria gracilis Pfeiff. (Cactaceae) growth switches from organized to unorganized way, producing a habituated organogenic callus which simultaneously regenerates morphologically normal as well as altered hyperhydric shoots. In this study, influence of tissue culture conditions on morphology of cactus spines of normal and hyperhydric shoots was investigated. Spines of pot-grown Mammillaria plants and of in vitro regenerated shoots were examined with stereo microscope and scanning electron microscope. The pot-grown plants had 16-17 spines per areole. In vitro grown normal shoots, even though they kept typical shoot morphology, had lower number of spines (11-12) and altered spine morphology. This difference was even more pronounced in spine number (six to seven) and morphology of the hyperhydric shoots. Scanning electron microscopy analysis revealed remarkable differences in micromorphology of spine surface between pot-grown and in vitro grown shoots. Spines of in vitro grown normal shoots showed numerous long trichomes, which were more elongated on spines of the hyperhydric shoots; the corresponding structures on spine surface of pot-grown plants were noticed only as small protrusions. Scanning electron microscopy morphometric studies showed that the spines of pot-grown plants were significantly longer compared to the spines of shoots grown in tissue culture. Moreover, transverse section shape varies from elliptical in pot-grown plants to circular in normal and hyperhydric shoots grown in vitro. Cluster and correspondence analyses performed on the scanning electron microscope obtained results suggest great variability among spines of pot-grown plants. Spines of in vitro grown normal and hyperhydric shoots showed low level of morphological variation among themselves despite the significant difference in shoot morphology.

Bartter syndrome presenting as poor weight gain and abdominal mass in an infant.

PubMed

Heffernan, Annie; Steffensen, Thora S; Gilbert-Barness, Enid; Perlman, Sharon

2008-01-01

Bartter syndrome, a group of disorders that encompasses multiple genetic defects with similar clinical presentation, has been divided into six different genotypes, according to different genetic defects, and into three main clinical variants (or phenotypes). Classic laboratory findings in all variants include hypochloremia, hypokalemia, and metabolic alkalosis with excessive excretion of chloride and potassium. Classic Bartter syndrome, neonatal Bartter syndrome, and Gitelman syndrome are the three main clinical variants. Classic Bartter syndrome and neonatal Bartter syndrome have defects in genes that affect transport channels in the ascending loop of Henle, where as in Gitleman syndrome the defect occurs in the transport channels of the distal convoluted tubule. Classic Bartter syndrome and neonatal Bartter syndrome have similar presenting symptoms, potential outcomes, and treatment, but different ages at presentation. Gitelman syndrome, a more benign condition than the other clinical variants, has the classic hallmark finding of hypomagnesemia and low to normal excretion of calcium. This differentiates it from the classic and neonatal variants of the disease. With early diagnosis and proper treatment, Bartter syndrome has a good prognosis. But failure to identify it can lead to tubulointerstitial nephritis and renal failure. We present a case of a 6-month-old boy with Bartter syndrome who presented with poor weight gain and an abdominal mass.

Spatio-temporal dynamics of brain mechanisms in aversive classical conditioning: high-density event-related potential and brain electrical tomography analyses.

PubMed

Pizzagalli, Diego A; Greischar, Lawrence L; Davidson, Richard J

2003-01-01

Social cognition, including complex social judgments and attitudes, is shaped by individual learning experiences, where affect often plays a critical role. Aversive classical conditioning-a form of associative learning involving a relationship between a neutral event (conditioned stimulus, CS) and an aversive event (unconditioned stimulus, US)-represents a well-controlled paradigm to study how the acquisition of socially relevant knowledge influences behavior and the brain. Unraveling the temporal unfolding of brain mechanisms involved appears critical for an initial understanding about how social cognition operates. Here, 128-channel ERPs were recorded in 50 subjects during the acquisition phase of a differential aversive classical conditioning paradigm. The CS+ (two fearful faces) were paired 50% of the time with an aversive noise (CS upward arrow + /Paired), whereas in the remaining 50% they were not (CS upward arrow + /Unpaired); the CS- (two different fearful faces) were never paired with the noise. Scalp ERP analyses revealed differences between CS upward arrow + /Unpaired and CS- as early as approximately 120 ms post-stimulus. Tomographic source localization analyses revealed early activation modulated by the CS+ in the ventral visual pathway (e.g. fusiform gyrus, approximately 120 ms), right middle frontal gyrus (approximately 176 ms), and precuneus (approximately 240 ms). At approximately 120 ms, the CS- elicited increased activation in the left insula and left middle frontal gyrus. These findings not only confirm a critical role of prefrontal, insular, and precuneus regions in aversive conditioning, but they also suggest that biologically and socially salient information modulates activation at early stages of the information processing flow, and thus furnish initial insight about how affect and social judgments operate.

How Does the Gibbs Inequality Condition Affect the Stability and Detachment of Floating Spheres from the Free Surface of Water?

PubMed

Feng, Dong-xia; Nguyen, Anh V

2016-03-01

Floating objects on the air-water interfaces are central to a number of everyday activities, from walking on water by insects to flotation separation of valuable minerals using air bubbles. The available theories show that a fine sphere can float if the force of surface tension and buoyancies can support the sphere at the interface with an apical angle subtended by the circle of contact being larger than the contact angle. Here we show that the pinning of the contact line at the sharp edge, known as the Gibbs inequality condition, also plays a significant role in controlling the stability and detachment of floating spheres. Specifically, we truncated the spheres with different angles and used a force sensor device to measure the force of pushing the truncated spheres from the interface into water. We also developed a theoretical modeling to calculate the pushing force that in combination with experimental results shows different effects of the Gibbs inequality condition on the stability and detachment of the spheres from the water surface. For small angles of truncation, the Gibbs inequality condition does not affect the sphere detachment, and hence the classical theories on the floatability of spheres are valid. For large truncated angles, the Gibbs inequality condition determines the tenacity of the particle-meniscus contact and the stability and detachment of floating spheres. In this case, the classical theories on the floatability of spheres are no longer valid. A critical truncated angle for the transition from the classical to the Gibbs inequality regimes of detachment was also established. The outcomes of this research advance our understanding of the behavior of floating objects, in particular, the flotation separation of valuable minerals, which often contain various sharp edges of their crystal faces.

Risk for ACPA-positive rheumatoid arthritis is driven by shared HLA amino acid polymorphisms in Asian and European populations

PubMed Central

Okada, Yukinori; Kim, Kwangwoo; Han, Buhm; Pillai, Nisha E.; Ong, Rick T.-H.; Saw, Woei-Yuh; Luo, Ma; Jiang, Lei; Yin, Jian; Bang, So-Young; Lee, Hye-Soon; Brown, Matthew A.; Bae, Sang-Cheol; Xu, Huji; Teo, Yik-Ying; de Bakker, Paul I.W.; Raychaudhuri, Soumya

2014-01-01

Previous studies have emphasized ethnically heterogeneous human leukocyte antigen (HLA) classical allele associations to rheumatoid arthritis (RA) risk. We fine-mapped RA risk alleles within the major histocompatibility complex (MHC) in 2782 seropositive RA cases and 4315 controls of Asian descent. We applied imputation to determine genotypes for eight class I and II HLA genes to Asian populations for the first time using a newly constructed pan-Asian reference panel. First, we empirically measured high imputation accuracy in Asian samples. Then we observed the most significant association in HLA-DRβ1 at amino acid position 13, located outside the classical shared epitope (Pomnibus = 6.9 × 10−135). The individual residues at position 13 have relative effects that are consistent with published effects in European populations (His > Phe > Arg > Tyr ≅ Gly > Ser)—but the observed effects in Asians are generally smaller. Applying stepwise conditional analysis, we identified additional independent associations at positions 57 (conditional Pomnibus = 2.2 × 10−33) and 74 (conditional Pomnibus = 1.1 × 10−8). Outside of HLA-DRβ1, we observed independent effects for amino acid polymorphisms within HLA-B (Asp9, conditional P = 3.8 × 10−6) and HLA-DPβ1 (Phe9, conditional P = 3.0 × 10−5) concordant with European populations. Our trans-ethnic HLA fine-mapping study reveals that (i) a common set of amino acid residues confer shared effects in European and Asian populations and (ii) these same effects can explain ethnically heterogeneous classical allelic associations (e.g. HLA-DRB1*09:01) due to allele frequency differences between populations. Our study illustrates the value of high-resolution imputation for fine-mapping causal variants in the MHC. PMID:25070946

Advancing Risk Assessment through the Application of Systems Toxicology

PubMed Central

Sauer, John Michael; Kleensang, André; Peitsch, Manuel C.; Hayes, A. Wallace

2016-01-01

Risk assessment is the process of quantifying the probability of a harmful effect to individuals or populations from human activities. Mechanistic approaches to risk assessment have been generally referred to as systems toxicology. Systems toxicology makes use of advanced analytical and computational tools to integrate classical toxicology and quantitative analysis of large networks of molecular and functional changes occurring across multiple levels of biological organization. Three presentations including two case studies involving both in vitro and in vivo approaches described the current state of systems toxicology and the potential for its future application in chemical risk assessment. PMID:26977253

Oxaliplatin loaded PLAGA microspheres: design of specific release profiles.

PubMed

Lagarce, F; Cruaud, O; Deuschel, C; Bayssas, M; Griffon-Etienne, G; Benoit, J

2002-08-21

Oxaliplatin loaded PLAGA microspheres have been prepared by solvent extraction process. Parameters affecting the release kinetics in vitro have been studied in order to design specific release profiles suitable for direct intra-tumoral injection. By varying the nature and the relative proportions of different polymers we managed to prepare microspheres with good encapsulation efficiency (75-90%) and four different release profiles: zero order kinetics (type II) and the classical sigmoïd release profile with three different sizes of plateau and burst. These results, if correlated with in vivo activity, are promising to enhance effectiveness of local tumor treatment.

Pflanzliche Zellkulturtechniken als Züchtungsschritt am Beispiel Raps

NASA Astrophysics Data System (ADS)

Hoffmann, Franz

1980-06-01

A supplementation of classical plant breeding is now necessary due to the limitations imposed by available genetic variability and the slowness of the method. Therefore, cell culture techniques could play an important role in the future. Using rape seed, in which plants derived from anther culture and in vitro mutagenesis are already field tested, it has been shown that, in this case, somatic genetics is very close to becoming a practical method. For most of the other crop plants, in particular the cereals, no such unconventional breeding techniques have yet been satisfactorily established for commercial use.

3-d brownian motion simulator for high-sensitivity nanobiotechnological applications.

PubMed

Toth, Arpád; Banky, Dániel; Grolmusz, Vince

2011-12-01

A wide variety of nanobiotechnologic applications are being developed for nanoparticle based in vitro diagnostic and imaging systems. Some of these systems make possible highly sensitive detection of molecular biomarkers. Frequently, the very low concentration of the biomarkers makes impossible the classical, partial differential equation-based mathematical simulation of the motion of the nanoparticles involved. We present a three-dimensional Brownian motion simulation tool for the prediction of the movement of nanoparticles in various thermal, viscosity, and geometric settings in a rectangular cuvette. For nonprofit users the server is freely available at the site http://brownian.pitgroup.org.

Essential oils: from extraction to encapsulation.

PubMed

El Asbahani, A; Miladi, K; Badri, W; Sala, M; Aït Addi, E H; Casabianca, H; El Mousadik, A; Hartmann, D; Jilale, A; Renaud, F N R; Elaissari, A

2015-04-10

Essential oils are natural products which have many interesting applications. Extraction of essential oils from plants is performed by classical and innovative methods. Numerous encapsulation processes have been developed and reported in the literature in order to encapsulate biomolecules, active molecules, nanocrystals, oils and also essential oils for various applications such as in vitro diagnosis, therapy, cosmetic, textile, food etc. Essential oils encapsulation led to numerous new formulations with new applications. This insures the protection of the fragile oil and controlled release. The most commonly prepared carriers are polymer particles, liposomes and solid lipid nanoparticles. Copyright © 2015 Elsevier B.V. All rights reserved.

Anaplasia and drug selection-independent overexpression of the multidrug resistance gene, MDR1, in Wilms' tumor.

PubMed

Re, G G; Willingham, M C; el Bahtimi, R; Brownlee, N A; Hazen-Martin, D J; Garvin, A J

1997-02-01

One reason for the failure of chemotherapy is the overexpression of the multidrug resistance gene, MDR1. The product of this gene is the multidrug transporter P-glycoprotein, an ATP-dependent pump that extrudes drugs from the cytoplasm. Some tumors inherently express P-glycoprotein, whereas others acquire the ability to do so after exposure to certain chemotherapeutic agents, often by the mechanism of gene amplification. Classical Wilms' tumors (nephroblastoma) typically respond to therapy and have a good prognosis. On the contrary, anaplastic Wilms' tumors are generally refractory to chemotherapy. These anaplastic variants are rare (4.5% of all Wilms' tumors reported in the United States), aggressive, and often fatal forms of tumor, which are commonly thought to result from the progression of classical Wilms' tumors. To investigate the basis for this differential response to therapy, we examined a number of classical and anaplastic Wilms' tumors for the expression of the MDR1 gene by immunohistochemical and mRNA analysis. Classical Wilms' tumors consistently did not express P-glycoprotein except in areas of tubular differentiation, as in normal kidney. Similarly, two of three anaplastic tumors failed to show P-glycoprotein expression. In contrast, cultured cells derived from a third anaplastic tumor, W4, exhibited strong P-glycoprotein expression and were drug resistant in vitro. Southern analysis revealed that W4 cells contained a single copy of the MDR1 gene per haploid genome similar to normal cells, demonstrating that the overexpression of MDR1 was not caused by gene amplification. Transcriptional activation of the MDR1 gene would be in keeping with the concept that p53 might act as a transcriptional repressor of the MDR1 gene.

Safety and immunogenicity of a cluster specific immunotherapy in children with bronchial asthma and mite allergy.

PubMed

Schubert, R; Eickmeier, O; Garn, H; Baer, P C; Mueller, T; Schulze, J; Rose, M A; Rosewich, M; Renz, H; Zielen, S

2009-01-01

Cluster specific immunotherapy (SIT) is a modern form of allergen immunotherapy allowing safe administration of high allergen doses in a short time interval compared to classic SIT. In the current study, we investigated the safety profile and immunological effect of cluster SIT in children with allergic asthma due to house dust mite allergy. A total of 34 children (6-18 years) with allergic asthma were assigned to cluster (n = 22) or classic SIT (n = 12). To achieve a maintenance dose of allergen extract, cluster patients received 14 injections of house dust mite allergen within 6 weeks, whereas the classic SIT group received 14 injections within 14 weeks. Safety was monitored by recording adverse events. Immunogenicity was measured by specific IgG(Mite) and IgG4(Mite), by antibody-blocking properties on basophil activation, and by the T cell subset transcription factors Foxp3, T-bet, and GATA-3. There were no significant differences in local and systemic side effects between the two groups. In the cluster group, serum levels of specific IgG(Mite) (p < 0.001) and specific IgG4(Mite) (p < 0.001) significantly increased after 8 weeks, while it took 12 weeks in the classic SIT group. These data were confirmed by blocking CD63 expression as well as release of cysteinyl leukotrienes after in vitro basophil stimulation. No differences in transcription factor expression were found in the two groups. Cluster SIT is safe in children. Additionally, our data demonstrated an even more rapid induction of specific immune tolerance. Cluster SIT is an attractive alternative to conventional up-dosing schedules with fewer consultations for the patients. (c) 2008 S. Karger AG, Basel.

Some conditions of compliance and resistance among hypnotic subjects.

PubMed

Levitt, E E; Baker, E L; Fish, R C

1990-04-01

Five experimental approaches to the resolution of the century-old Bernheim/Janet dispute and the issue of involuntariness or coercion (the classical suggestion effect) are presented. Four experiments are reported that follow one of the approaches: attempts to induce hypnotic subjects to resist suggestions made in trance. The design is one in which a "resistance instructor" proposes a reward for the resisting subject. Tentative inferences from the results are that the classical suggestion effect is found with a small number of subjects; for a larger number of subjects there is no classical suggestion effect, and for many subjects the outcome is equivocal. Relational factors in the hypnotic dyad influence responsiveness in the subject, the effect being least for those whose susceptibility is high.

Protein Binding: Do We Ever Learn?▿

PubMed Central

Zeitlinger, Markus A.; Derendorf, Hartmut; Mouton, Johan W.; Cars, Otto; Craig, William A.; Andes, David; Theuretzbacher, Ursula

2011-01-01

Although the influence of protein binding (PB) on antibacterial activity has been reported for many antibiotics and over many years, there is currently no standardization for pharmacodynamic models that account for the impact of protein binding of antimicrobial agents in vitro. This might explain the somewhat contradictory results obtained from different studies. Simple in vitro models which compare the MIC obtained in protein-free standard medium versus a protein-rich medium are prone to methodological pitfalls and may lead to flawed conclusions. Within in vitro test systems, a range of test conditions, including source of protein, concentration of the tested antibiotic, temperature, pH, electrolytes, and supplements may influence the impact of protein binding. As new antibiotics with a high degree of protein binding are in clinical development, attention and action directed toward the optimization and standardization of testing the impact of protein binding on the activity of antibiotics in vitro become even more urgent. In addition, the quantitative relationship between the effects of protein binding in vitro and in vivo needs to be established, since the physiological conditions differ. General recommendations for testing the impact of protein binding in vitro are suggested. PMID:21537013

Uterine sacculation.

PubMed

Spearing, G J

1978-01-01

A case of uterine sacculation is reported in which a classic cesarean section was required for safe delivery. The definition and diagnosis of the condition and some difficulties in management are discussed.

Psychosocial stressors and the short life spans of legendary jazz musicians.

PubMed

Patalano, F

2000-04-01

Mean age at death of 168 legendary jazz musicians and 100 renowned classical musicians were compared to examine whether psychosocial stressors such as severe substance abuse, haphazard working conditions, lack of acceptance of jazz as an art form in the United States, marital and family discord, and a vagabond life style may have contributed to shortened life spans for the jazz musicians. Analysis indicated that the jazz musicians died at an earlier age (57.2 yr.) than the classical musicians (73.3 yr.).

Unicorns in the world of chemical bonding models.

PubMed

Frenking, Gernot; Krapp, Andreas

2007-01-15

The appearance and the significance of heuristically developed bonding models are compared with the phenomenon of unicorns in mythical saga. It is argued that classical bonding models played an essential role for the development of the chemical science providing the language which is spoken in the territory of chemistry. The advent and the further development of quantum chemistry demands some restrictions and boundary conditions for classical chemical bonding models, which will continue to be integral parts of chemistry. Copyright (c) 2006 Wiley Periodicals, Inc.

Existence of equilibria in quantum Bertrand-Edgeworth duopoly game

NASA Astrophysics Data System (ADS)

Sekiguchi, Yohei; Sakahara, Kiri; Sato, Takashi

2012-12-01

Both classical and quantum version of two models of price competition in duopoly market, the one is realistic and the other is idealized, are investigated. The pure strategy Nash equilibria of the realistic model exists under stricter condition than that of the idealized one in the classical form game. This is the problem known as Edgeworth paradox in economics. In the quantum form game, however, the former converges to the latter as the measure of entanglement goes to infinity.

Extinction Phenomena: A Biologic Perspective on How and Why Psychoanalysis Works

PubMed Central

Brakel, Linda A. W.

2011-01-01

This article presents the view that much of the success of classical psychoanalysis is centrally predicated on its biological potency; focusing not on neuropsychology, but on the biology of conditioning. The argument suggests that features of classic psychoanalytic technique – the couch, meetings several times per week with both parties present, and free association – uniquely facilitate intense transferences of various sorts, and that these in turn constitute the multiple and diverse extinction trials necessary to best approximate extinction. PMID:21927610

Mathematical modeling of HIV-like particle assembly in vitro.

PubMed

Liu, Yuewu; Zou, Xiufen

2017-06-01

In vitro, the recombinant HIV-1 Gag protein can generate spherical particles with a diameter of 25-30 nm in a fully defined system. It has approximately 80 building blocks, and its intermediates for assembly are abundant in geometry. Accordingly, there are a large number of nonlinear equations in the classical model. Therefore, it is difficult to compute values of geometry parameters for intermediates and make the mathematical analysis using the model. In this work, we develop a new model of HIV-like particle assembly in vitro by using six-fold symmetry of HIV-like particle assembly to decrease the number of geometry parameters. This method will greatly reduce computational costs and facilitate the application of the model. Then, we prove the existence and uniqueness of the positive equilibrium solution for this model with 79 nonlinear equations. Based on this model, we derive the interesting result that concentrations of all intermediates at equilibrium are independent of three important parameters, including two microscopic on-rate constants and the size of nucleating structure. Before equilibrium, these three parameters influence the concentration variation rates of all intermediates. We also analyze the relationship between the initial concentration of building blocks and concentrations of all intermediates. Furthermore, the bounds of concentrations of free building blocks and HIV-like particles are estimated. These results will be helpful to guide HIV-like particle assembly experiments and improve our understanding of the assembly dynamics of HIV-like particles in vitro. Copyright © 2017 Elsevier Inc. All rights reserved.

Cytochrome P450-mediated warfarin metabolic ability is not a critical determinant of warfarin sensitivity in avian species: In vitro assays in several birds and in vivo assays in chicken.

PubMed

Watanabe, Kensuke P; Kawata, Minami; Ikenaka, Yoshinori; Nakayama, Shouta M M; Ishii, Chihiro; Darwish, Wageh Sobhi; Saengtienchai, Aksorn; Mizukawa, Hazuki; Ishizuka, Mayumi

2015-10-01

Coumarin-derivative anticoagulant rodenticides used for rodent control are posing a serious risk to wild bird populations. For warfarin, a classic coumarin derivative, chickens have a high median lethal dose (LD50), whereas mammalian species generally have much lower LD50. Large interspecies differences in sensitivity to warfarin are to be expected. The authors previously reported substantial differences in warfarin metabolism among avian species; however, the actual in vivo pharmacokinetics have yet to be elucidated, even in the chicken. In the present study, the authors sought to provide an in-depth characterization of warfarin metabolism in birds using in vivo and in vitro approaches. A kinetic analysis of warfarin metabolism was performed using liver microsomes of 4 avian species, and the metabolic abilities of the chicken and crow were much higher in comparison with those of the mallard and ostrich. Analysis of in vivo metabolites from chickens showed that excretions predominantly consisted of 4'-hydroxywarfarin, which was consistent with the in vitro results. Pharmacokinetic analysis suggested that chickens have an unexpectedly long half-life despite showing high metabolic ability in vitro. The results suggest that the half-life of warfarin in other bird species could be longer than that in the chicken and that warfarin metabolism may not be a critical determinant of species differences with respect to warfarin sensitivity. © 2015 SETAC.

[In silico, in vitro, in omic experimental models and drug safety evaluation].

PubMed

Claude, Nancy; Goldfain-Blanc, Françoise; Guillouzo, André

2009-01-01

Over the last few decades, toxicology has benefited from scientific, technical, and bioinformatic developments relating to patient safety assessment during clinical and drug marketing studies. Based on this knowledge, new in silico, in vitro, and "omic" experimental models are emerging. Although these models cannot currently replace classic safety evaluations performed on laboratory animals, they allow compounds with unacceptable toxicity to be rejected in the early stages of drug development, thereby reducing the number of laboratory animals needed. In addition, because these models are particularly adapted to mechanistic studies, they can help to improve the relevance of the data obtained, thus enabling better prevention and screening of the adverse effects that may occur in humans. Much progress remains to be done, especially in the field of validation. Nevertheless, current efforts by industrial, academic laboratories, and regulatory agencies should, in coming years, significantly improve preclinical drug safety evaluation thanks to the integration of these new methods into the drug research and development process.

Antibiotic-mediated antagonism leads to a bacterial game of rock-paper-scissors in vivo

NASA Astrophysics Data System (ADS)

Kirkup, Benjamin C.; Riley, Margaret A.

2004-03-01

Colicins are narrow-spectrum antibiotics produced by and active against Escherichia coli and its close relatives. Colicin-producing strains cannot coexist with sensitive or resistant strains in a well-mixed culture, yet all three phenotypes are recovered in natural populations. Recent in vitro results conclude that strain diversity can be promoted by colicin production in a spatially structured, non-transitive interaction, as in the classic non-transitive model rock-paper-scissors (RPS). In the colicin version of the RPS model, strains that produce colicins (C) kill sensitive (S) strains, which outcompete resistant (R) strains, which outcompete C strains. Pairwise in vitro competitions between these three strains are resolved in a predictable order (C beats S, S beats R, and R beats C), but the complete system of three strains presents the opportunity for dynamic equilibrium. Here we provide conclusive evidence of an in vivo antagonistic role for colicins and show that colicins (and potentially other bacteriocins) may promote, rather than eliminate, microbial diversity in the environment.

Boar semen controlled delivery system: storage and in vitro spermatozoa release.

PubMed

Torre, M L; Faustini, M; Norberti, R; Stacchezzini, S; Maggi, L; Maffeo, G; Conte, U; Vigo, D

2002-12-13

Swine spermatozoa were encapsulated in barium alginate and protamine-barium alginate membranes to lengthen their preservation time and to provide a means of controlling their release. Precocious acrosome reactions and secondary anomalies were measured as indices of semen quality. These characteristics were observed for two forms of encapsulated spermatozoa when stored at 18 and 38 degrees C for 24 h and for semen diluted in a classical extender at both temperatures. The results indicate that encapsulation enhances semen preservation, providing protection against membrane damage upon dilution. The effect is even more evident at the higher temperature (38 degrees C), where cell metabolism is higher. An in vitro release test of spermatozoa showed a massive cell delivery from barium alginate capsules within 6 h, and a slow release from protamine-barium alginate capsules. The properties of spermatozoa 24 h after release did not differ from the semen stored at the same temperature in capsules, indicating that the release process does not impair semen quality.

Concerted In Vitro Trimming of Viral HLA-B27-Restricted Ligands by Human ERAP1 and ERAP2 Aminopeptidases

PubMed Central

Lorente, Elena; Barriga, Alejandro; Johnstone, Carolina; Mir, Carmen; Jiménez, Mercedes; López, Daniel

2013-01-01

In the classical human leukocyte antigen (HLA) class I antigen processing and presentation pathway, the antigenic peptides are generated from viral proteins by multiple proteolytic cleavages of the proteasome (and in some cases other cytosolic proteases) and transported to the endoplasmic reticulum (ER) lumen where they are exposed to aminopeptidase activity. In human cells, two different ER-resident enzymes, ERAP1 and ERAP2, can trim the N-terminally extended residues of peptide precursors. In this study, the possible cooperative effect of generating five naturally processed HLA-B27 ligands by both proteases was analyzed. We identified differences in the products obtained with increased detection of natural HLA-B27 ligands by comparing double versus single enzyme digestions by mass spectrometry analysis. These in vitro data suggest that each enzyme can use the degradation products of the other as a substrate for new N-terminal trimming, indicating concerted aminoproteolytic activity of ERAP 1 and ERAP2. PMID:24223975

Concerted in vitro trimming of viral HLA-B27-restricted ligands by human ERAP1 and ERAP2 aminopeptidases.

PubMed

Lorente, Elena; Barriga, Alejandro; Johnstone, Carolina; Mir, Carmen; Jiménez, Mercedes; López, Daniel

2013-01-01

In the classical human leukocyte antigen (HLA) class I antigen processing and presentation pathway, the antigenic peptides are generated from viral proteins by multiple proteolytic cleavages of the proteasome (and in some cases other cytosolic proteases) and transported to the endoplasmic reticulum (ER) lumen where they are exposed to aminopeptidase activity. In human cells, two different ER-resident enzymes, ERAP1 and ERAP2, can trim the N-terminally extended residues of peptide precursors. In this study, the possible cooperative effect of generating five naturally processed HLA-B27 ligands by both proteases was analyzed. We identified differences in the products obtained with increased detection of natural HLA-B27 ligands by comparing double versus single enzyme digestions by mass spectrometry analysis. These in vitro data suggest that each enzyme can use the degradation products of the other as a substrate for new N-terminal trimming, indicating concerted aminoproteolytic activity of ERAP 1 and ERAP2.

A single molecule perspective on the functional diversity of in vitro evolved β-glucuronidase.

PubMed

Liebherr, Raphaela B; Renner, Max; Gorris, Hans H

2014-04-23

The mechanisms that drive the evolution of new enzyme activity have been investigated by comparing the kinetics of wild-type and in vitro evolved β-glucuronidase (GUS) at the single molecule level. Several hundred single GUS molecules were separated in large arrays of 62,500 ultrasmall reaction chambers etched into the surface of a fused silica slide to observe their individual substrate turnover rates in parallel by fluorescence microscopy. Individual GUS molecules feature long-lived but divergent activity states, and their mean activity is consistent with classic Michaelis-Menten kinetics. The large number of single molecule substrate turnover rates is representative of the activity distribution within an entire enzyme population. Partially evolved GUS displays a much broader activity distribution among individual enzyme molecules than wild-type GUS. The broader activity distribution indicates a functional division of work between individual molecules in a population of partially evolved enzymes that-as so-called generalists-are characterized by their promiscuous activity with many different substrates.

In vitro phosphorylation of insulin receptor substrate 1 by protein kinase C-zeta: functional analysis and identification of novel phosphorylation sites.

PubMed

Sommerfeld, Mark R; Metzger, Sabine; Stosik, Magdalene; Tennagels, Norbert; Eckel, Jürgen

2004-05-18

Protein kinase C-zeta (PKC-zeta) participates both in downstream insulin signaling and in the negative feedback control of insulin action. Here we used an in vitro approach to identify PKC-zeta phosphorylation sites within insulin receptor substrate 1 (IRS-1) and to characterize the functional implications. A recombinant IRS-1 fragment (rIRS-1(449)(-)(664)) containing major tyrosine motifs for interaction with phosphatidylinositol (PI) 3-kinase strongly associated to the p85alpha subunit of PI 3-kinase after Tyr phosphorylation by the insulin receptor. Phosphorylation of rIRS-1(449)(-)(664) by PKC-zeta induced a prominent inhibition of this process with a mixture of classical PKC isoforms being less effective. Both PKC-zeta and the classical isoforms phosphorylated rIRS-1(449)(-)(664) on Ser(612). However, modification of this residue did not reduce the affinity of p85alpha binding to pTyr-containing peptides (amino acids 605-615 of rat IRS-1), as determined by surface plasmon resonance. rIRS-1(449)(-)(664) was then phosphorylated by PKC-zeta using [(32)P]ATP and subjected to tryptic phosphopeptide mapping based on two-dimensional HPLC coupled to mass spectrometry. Ser(498) and Ser(570) were identified as novel phosphoserine sites targeted by PKC-zeta. Both sites were additionally confirmed by phosphopeptide mapping of the corresponding Ser --> Ala mutants of rIRS-1(449)(-)(664). Ser(570) was specifically targeted by PKC-zeta, as shown by immunoblotting with a phosphospecific antiserum against Ser(570) of IRS-1. Binding of p85alpha to the S570A mutant was less susceptible to inhibition by PKC-zeta, when compared to the S612A mutant. In conclusion, our in vitro data demonstrate a strong inhibitory action of PKC-zeta at the level of IRS-1/PI 3-kinase interaction involving multiple serine phosphorylation sites. Whereas Ser(612) appears not to participate in the negative control of insulin signaling, Ser(570) may at least partly contribute to this process.

The effects of an overnight holding of whole blood at room temperature on haemoglobin modification and in vitro markers of red blood cell aging.

PubMed

Eckstein, M; Zimmermann, R; Roth, T; Hauck-Dlimi, B; Strasser, E F; Xiang, W

2015-05-01

Some effects of the red blood cell (RBC) storage lesion are well documented whereas others are not. Whether a period of room temperature hold (RTH) during RBC production enhances the RBC storage lesion has remained controversial. In this study, we compared whole blood (WB)-derived RBCs produced after 24-h RTH with rapidly cooled (RC) RBCs and tested them for classical metabolic markers and signs of oxidative damage. SAGM-RBCs were prepared from mixed and split pairs (n = 12) of WB units. RBCs prepared after a 24-h period of RTH on day+1 after collection (RTH-RBCs) were compared with RC-RBCs. All RBCs were stored at 4°C for 42 days with assay of in vitro variables on days+1, +15, +22, +29 and +42. The study examined standard quality parameters, glutathione, catalase and superoxide dismutase (SOD) activities, and indicative markers of oxidative cell damage including post-translational haemoglobin modification, malondialdehyde (MDA), and phosphatidylserine expression. RTH-RBCs exhibited decreased levels of potassium (1·98 ± 0·26 vs. 5·23 ± 0·65 mmol/l) and of 2,3-diphosphoglycerate (2,3-DPG) on day+1 compared with RC-RBCs. Haemolysis rate on day+42 was higher in RTH-RBCs than in RC-RBCs (0·52 ± 0·13 vs. 0·37 ± 0·12%). The phosphatidylserine expression amounted to 0·25 ± 0·20% in RTH-RBCs and 0·07 ± 0·12% in RC-RBCs. Haemoglobin modification was not different between both RBC groups. RTH-RBCs showed slightly higher MDA concentration on days +29 and +42. RC-RBCs and RTH-RBCs show only small differences of classical in vitro parameters and no relevant differences in antioxidative metabolism and oxidative haemoglobin modification. These findings do not explain the loss observed in in vivo survival studies with RBCs. © 2015 International Society of Blood Transfusion.

In vitro prion protein conversion suggests risk of bighorn sheep (Ovis canadensis) to transmissible spongiform encephalopathies

PubMed Central

2013-01-01

Background Transmissible spongiform encephalopathies (TSEs) affect both domestic sheep (scrapie) and captive and free-ranging cervids (chronic wasting disease; CWD). The geographical range of bighorn sheep (Ovis canadensis; BHS) overlaps with states or provinces that have contained scrapie-positive sheep or goats and areas with present epizootics of CWD in cervids. No TSEs have been documented in BHS, but the susceptibility of this species to TSEs remains unknown. Results We acquired a library of BHS tissues and found no evidence of preexisting TSEs in these animals. The prion protein gene (Prnp) in all BHS in our library was identical to scrapie-susceptible domestic sheep (A136R154Q171 genotype). Using an in vitro prion protein conversion assay, which has been previously used to assess TSE species barriers and, in our study appears to recollect known species barriers in mice, we assessed the potential transmissibility of TSEs to BHS. As expected based upon Prnp genotype, we observed BHS prion protein conversion by classical scrapie agent and evidence for a species barrier between transmissible mink encephalopathy (TME) and BHS. Interestingly, our data suggest that the species barrier of BHS to white-tailed deer or wapiti CWD agents is likely low. We also used protein misfolding cyclic amplification to confirm that CWD, but not TME, can template prion protein misfolding in A136R154Q171 genotype sheep. Conclusions Our results indicate the in vitro conversion assay used in our study does mimic the species barrier of mice to the TSE agents that we tested. Based on Prnp genotype and results from conversion assays, BHS are likely to be susceptible to infection by classical scrapie. Despite mismatches in amino acids thought to modulate prion protein conversion, our data indicate that A136R154Q171 genotype sheep prion protein is misfolded by CWD agent, suggesting that these animals could be susceptible to CWD. Further investigation of TSE transmissibility to BHS, including animal studies, is warranted. The lack of reported TSEs in BHS may be attributable to other host factors or a lack of TSE surveillance in this species. PMID:23938169

In vitro prion protein conversion suggests risk of bighorn sheep (Ovis canadensis) to transmissible spongiform encephalopathies

USGS Publications Warehouse

Johnson, Christopher J.; Morawski, A.R.; Carlson, C.M.; Chang, H.

2013-01-01

Background: Transmissible spongiform encephalopathies (TSEs) affect both domestic sheep (scrapie) and captive and free-ranging cervids (chronic wasting disease; CWD). The geographical range of bighorn sheep (Ovis canadensis; BHS) overlaps with states or provinces that have contained scrapie-positive sheep or goats and areas with present epizootics of CWD in cervids. No TSEs have been documented in BHS, but the susceptibility of this species to TSEs remains unknown. Results: We acquired a library of BHS tissues and found no evidence of preexisting TSEs in these animals. The prion protein gene (Prnp) in all BHS in our library was identical to scrapie-susceptible domestic sheep (A136R 154Q171). Using an in vitro prion protein conversion assay, which has been previously used to assess TSE species barriers and, in our study appears to recollect known species barriers in mice, we assessed the potential transmissibility of TSEs to BHS. As expected based upon Prnp genotype, we observed BHS prion protein conversion by classical scrapie agent and evidence for a species barrier between transmissible mink encephalopathy (TME) and BHS. Interestingly, our data suggest that the species barrier of BHS to white-tailed deer or wapiti CWD agents is likely low. We also used protein misfolding cyclic amplification to confirm that CWD, but not TME, can template prion protein misfolding in A136R 154Q171genotype sheep. Conclusions: Our results indicate the in vitro conversion assay used in our study does mimic the species barrier of mice to the TSE agents that we tested. Based on Prnp genotype and results from conversion assays, BHS are likely to be susceptible to infection by classical scrapie. Despite mismatches in amino acids thought to modulate prion protein conversion, our data indicate that A136R154Q171 genotype sheep prion protein is misfolded by CWD agent, suggesting that these animals could be susceptible to CWD. Further investigation of TSE transmissibility to BHS, including animal studies, is warranted. The lack of reported TSEs in BHS may be attributable to other host factors or a lack of TSE surveillance in this species.

Artefactual nanoparticle activation of the inflammasome platform: in vitro evidence with a nano-formed calcium phosphate

PubMed Central

Pele, Laetitia; Haas, Carolin T; Hewitt, Rachel; Faria, Nuno; Brown, Andy; Powell, Jonathan

2015-01-01

Aim To determine whether in vitro experimental conditions dictate cellular activation of the inflammasome by apatitic calcium phosphate nanoparticles. Material & methods The responses of blood-derived primary human cells to in situ-formed apatite were investigated under different experimental conditions to assess the effect of aseptic culture, cell rest and duration of particle exposure. Cell death and particle uptake were assessed, while IL-1β and caspase 1 responses, with and without lipopolysaccharide prestimulation, were evaluated as markers of inflammasome activation. Results Under carefully addressed experimental conditions, apatitic nanoparticles did not induce cell death or engage the inflammasome platform, although both could be triggered through artefacts of experimentation. Conclusion In vitro studies often predict that engineered nanoparticles, such as synthetic apatite, are candidates for inflammasome activation and, hence, are toxic. However, the experimental setting must be very carefully considered as it may promote false-positive outcomes. PMID:24991724

Ultrastructure of cuticle deposited inPlodia interpunctella wing discs after variousβ-ecdysone treatments in vitro.

PubMed

Dutkowski, A B; Oberlander, H; Leach, C E

1977-06-01

Wing discs of the Indian meal moth may be cultured for extended periods in vitro. The discs produced a tanned cuticle after continuous incubation with β-ecdysone in medium conditioned with fat body or after a 24-h pulse incubation with β-ecdysone in plain medium. We investigated the ultrastructure of the cuticle deposited by such discs. We found that the treatment that produced the most complete cuticle in vitro was the 24-h pulse of hormone. We observed that cuticle formation in vitro was not "all-or-none." Depending on culture conditions, discs produced cuticulin only, complete epicuticle, epicuticle plus diffuse endocuticle, epicuticle plus lamellate endocuticle, or even multiple layers of cuticle. The ultrastructural evidence suggests that continuous incubation with β-ecdysone in plain medium does not always inhibit cuticle formationper se, but does prevent tanning of the partially formed cuticle.

Quantum Secure Conditional Direct Communication via EPR Pairs

NASA Astrophysics Data System (ADS)

Gao, Ting; Yan, Fengli; Wang, Zhixi

Two schemes for quantum secure conditional direct communication are proposed, where a set of EPR pairs of maximally entangled particles in Bell states, initially made by the supervisor Charlie, but shared by the sender Alice and the receiver Bob, functions as quantum information channels for faithful transmission. After insuring the security of the quantum channel and obtaining the permission of Charlie (i.e., Charlie is trustworthy and cooperative, which means the "conditional" in the two schemes), Alice and Bob begin their private communication under the control of Charlie. In the first scheme, Alice transmits secret message to Bob in a deterministic manner with the help of Charlie by means of Alice's local unitary transformations, both Alice and Bob's local measurements, and both of Alice and Charlie's public classical communication. In the second scheme, the secure communication between Alice and Bob can be achieved via public classical communication of Charlie and Alice, and the local measurements of both Alice and Bob. The common feature of these protocols is that the communications between two communication parties Alice and Bob depend on the agreement of the third side Charlie. Moreover, transmitting one bit secret message, the sender Alice only needs to apply a local operation on her one qubit and send one bit classical information. We also show that the two schemes are completely secure if quantum channels are perfect.

Flavivirus RNA Synthesis in vitro

PubMed Central

Padmanabhan, Radhakrishnan; Takhampunya, Ratree; Teramoto, Tadahisa; Choi, Kyung H.

2015-01-01

Summary Establishment of in vitro systems to study mechanisms of RNA synthesis for positive strand RNA viruses have been very useful in the past and have shed light on the composition of protein and RNA components, optimum conditions, the nature of the products formed, cis-acting RNA elements and trans-acting protein factors required for efficient synthesis. In this review, we summarize our current understanding regarding the requirements for flavivirus RNA synthesis in vitro. We describe details of reaction conditions, the specificity of template used by either the multi-component membrane-bound viral replicase complex or by purified, recombinant RNA-dependent RNA polymerase. We also discuss future perspectives to extend the boundaries of our knowledge. PMID:26272247

On the dynamical and geometrical symmetries of Keplerian motion

NASA Astrophysics Data System (ADS)

Wulfman, Carl E.

2009-05-01

The dynamical symmetries of classical, relativistic and quantum-mechanical Kepler systems are considered to arise from geometric symmetries in PQET phase space. To establish their interconnection, the symmetries are related with the aid of a Lie-algebraic extension of Dirac's correspondence principle, a canonical transformation containing a Cunningham-Bateman inversion, and a classical limit involving a preliminary canonical transformation in ET space. The Lie-algebraic extension establishes the conditions under which the uncertainty principle allows the local dynamical symmetry of a quantum-mechanical system to be the same as the geometrical phase-space symmetry of its classical counterpart. The canonical transformation converts Poincaré-invariant free-particle systems into ISO(3,1) invariant relativistic systems whose classical limit produces Keplerian systems. Locally Cartesian relativistic PQET coordinates are converted into a set of eight conjugate position and momentum coordinates whose classical limit contains Fock projective momentum coordinates and the components of Runge-Lenz vectors. The coordinate systems developed via the transformations are those in which the evolution and degeneracy groups of the classical system are generated by Poisson-bracket operators that produce ordinary rotation, translation and hyperbolic motions in phase space. The way in which these define classical Keplerian symmetries and symmetry coordinates is detailed. It is shown that for each value of the energy of a Keplerian system, the Poisson-bracket operators determine two invariant functions of positions and momenta, which together with its regularized Hamiltonian, define the manifold in six-dimensional phase space upon which motions evolve.

Quantum walks with tuneable self-avoidance in one dimension

PubMed Central

Camilleri, Elizabeth; Rohde, Peter P.; Twamley, Jason

2014-01-01

Quantum walks exhibit many unique characteristics compared to classical random walks. In the classical setting, self-avoiding random walks have been studied as a variation on the usual classical random walk. Here the walker has memory of its previous locations and preferentially avoids stepping back to locations where it has previously resided. Classical self-avoiding random walks have found numerous algorithmic applications, most notably in the modelling of protein folding. We consider the analogous problem in the quantum setting – a quantum walk in one dimension with tunable levels of self-avoidance. We complement a quantum walk with a memory register that records where the walker has previously resided. The walker is then able to avoid returning back to previously visited sites or apply more general memory conditioned operations to control the walk. We characterise this walk by examining the variance of the walker's distribution against time, the standard metric for quantifying how quantum or classical a walk is. We parameterise the strength of the memory recording and the strength of the memory back-action on the walker, and investigate their effect on the dynamics of the walk. We find that by manipulating these parameters, which dictate the degree of self-avoidance, the walk can be made to reproduce ideal quantum or classical random walk statistics, or a plethora of more elaborate diffusive phenomena. In some parameter regimes we observe a close correspondence between classical self-avoiding random walks and the quantum self-avoiding walk. PMID:24762398

Classicality condition on a system observable in a quantum measurement and a relative-entropy conservation law

NASA Astrophysics Data System (ADS)

Kuramochi, Yui; Ueda, Masahito

2015-03-01

We consider the information flow on a system observable X corresponding to a positive-operator-valued measure under a quantum measurement process Y described by a completely positive instrument from the viewpoint of the relative entropy. We establish a sufficient condition for the relative-entropy conservation law which states that the average decrease in the relative entropy of the system observable X equals the relative entropy of the measurement outcome of Y , i.e., the information gain due to measurement. This sufficient condition is interpreted as an assumption of classicality in the sense that there exists a sufficient statistic in a joint successive measurement of Y followed by X such that the probability distribution of the statistic coincides with that of a single measurement of X for the premeasurement state. We show that in the case when X is a discrete projection-valued measure and Y is discrete, the classicality condition is equivalent to the relative-entropy conservation for arbitrary states. The general theory on the relative-entropy conservation is applied to typical quantum measurement models, namely, quantum nondemolition measurement, destructive sharp measurements on two-level systems, a photon counting, a quantum counting, homodyne and heterodyne measurements. These examples except for the nondemolition and photon-counting measurements do not satisfy the known Shannon-entropy conservation law proposed by Ban [M. Ban, J. Phys. A: Math. Gen. 32, 1643 (1999), 10.1088/0305-4470/32/9/012], implying that our approach based on the relative entropy is applicable to a wider class of quantum measurements.

Role of indigenous herbs in the management of Alzheimer's disease

PubMed Central

Nishteswar, K.; Joshi, Hemang; Karra, Rahul Dutt

2014-01-01

Ageing is a natural phenomenon and decline of physiological and structural changes are incurable in advancing years of human life. When such degenerative changes occur in the brain they may lead to dementia and other memory related conditions. The Ayurvedic classics identified the importance of higher faculties dealing with memory and introduced a separate group of drugs namely Medhya Rasayanas. Regular intake of such drugs will help to prevent the onset of degenerative changes in the brain prematurely. Ayurveda can play a useful role in the management of such geriatric conditions. The current review has been done with a view to update documented Ayurvedic therapeutic modalities for certain geriatric conditions suggested by Ayurvedic classics in the management of diseases called Vātavyādhi (nervous system disorders), which also include conditions related to memory functions. Recent studies have started validating the claims recorded in Ayurvedic texts. The pathogenesis and remedies for Vātavyādhi documented in Ayurvedic classics have been reviewed with special emphasis on disorders related to dementia. A review of recent researches on the herbs mentioned in management of vāta disorders including dementia have been done to understand their role in management of Alzheimer's disease (AD). There are many herbs of ethno-medicinal source studied experimentally for their potential in treatment of AD. A judicious combination of modern research methodology and Ayurvedic principles could go a long way in the management and care of AD which is going to be a heavy burden on the society in the future. PMID:25737604

Subcellular, Cellular and Circuit Mechanisms underlying Classical Conditioning in Hermissenda crassicornis

PubMed Central

2009-01-01

A breakthrough for studying the neuronal basis of learning emerged when invertebrates with simple nervous systems, such as the sea slug Hermissenda crassicornis, were shown to exhibit classical conditioning. Hermissenda learns to associate light with turbulence: prior to learning, naive animals move toward light (phototaxis) and contract their foot in response to turbulence; after learning, conditioned animals delay phototaxis in response to light. The photoreceptors of the eye, which receive monosynaptic inputs from statocyst hair cells, are both sensory neurons and the first site of sensory convergence. The memory of light associated with turbulence is stored as changes in intrinsic and synaptic currents in these photoreceptors. The subcellular mechanisms producing these changes include activation of protein kinase C and MAP kinase, which act as coincidence detectors because they are activated by convergent signaling pathways. Pathways of interneurons and motorneurons, where additional changes in excitability and synaptic connections are found, contribute to delayed phototaxis. Bursting activity recorded at several points suggest the existence of small networks that produce complex spatio-temporal firing patterns. Thus, the change in behavior may be produced by a non-linear transformation of spatio-temporal firing patterns caused by plasticity of synaptic and intrinsic channels. The change in currents and the activation of PKC and MAPK produced by associative learning are similar to that observed in hippocampal and cerebellar neurons after rabbit classical conditioning, suggesting that these represent general mechanisms of memory storage. Thus, the knowledge gained from further study of Hermissenda will continue to illuminate mechanisms of mammalian learning. PMID:16437555

Physiological Strain in French Vineyard Workers Wearing Protective Equipment to Conduct Re-Entry Tasks in Humid Conditions.

PubMed

Grimbuhler, Sonia; Viel, Jean-François

2018-06-19

The proper use of personal protective equipment (PPE) plays an important role in reducing exposure to pesticides in vineyard farming activities, including re-entry tasks. However, discomfort from clothing systems may increase the physiological burden on workers. We compared the physiological burdens of vineyard workers wearing three different types of PPE during canopy management in field humid conditions while accounting for occupational, climatic, and geographical environments. The study was conducted in the Bordeaux vineyards of southern France during June 2012. A total of 42 workers from seven vineyards consented to field observations. The following PPE garments were randomly allocated: HF Estufa polyamide (Brisa®), Tyvek® Classic Plus, and Tychem® C Standard. Participant sociodemographic characteristics were collected using a structured questionnaire. Skin temperature and heart rate were monitored continuously using portable devices. Multivariate multilevel linear regression models were performed to account for the hierarchical structure of data. No significant difference was found for mean skin temperature during work. Regardless of the cardiac strain parameter considered, the Tyvek® Classic Plus garment produced the poorest results (P ≤ 0.03). Under the very humid conditions encountered during the field study, the thinness and breathability of the Tyvek® Classic Plus garment resulted in undergarment humidity, imposing additional physiological burden on vineyard workers. These results confirm that the idea of using generic coveralls in any farming activity is unsuitable. Compromises should be created between physiological costs and protection, depending on the agricultural task performed, the crop grown, and the environmental conditions encountered.

Physiological differences and changes in global DNA methylation levels in Agave angustifolia Haw. albino variant somaclones during the micropropagation process.

PubMed

Duarte-Aké, Fátima; Castillo-Castro, Eduardo; Pool, Felipe Barredo; Espadas, Francisco; Santamaría, Jorge M; Robert, Manuel L; De-la-Peña, Clelia

2016-12-01

Global DNA methylation changes caused by in vitro conditions are associated with the subculturing and phenotypic variation in Agave angustifolia Haw. While the relationship between the development of albinism and in vitro culture is well documented, the role of epigenetic processes in this development leaves some important questions unanswered. During the micropropagation of Agave angustifolia Haw., we found three different phenotypes, green (G), variegated (V) and albino (A). To understand the physiological and epigenetic differences among the somaclones, we analyzed several morphophysiological parameters and changes in the DNA methylation patterns in the three phenotypes during their in vitro development. We found that under in vitro conditions, the V plantlets maintained their CAM photosynthetic capacity, while the A variant showed no pigments and lost its CAM photosynthetic ability. Epigenetic analysis revealed that global DNA methylation increased in the G phenotype during the first two subcultures. However, after that time, DNA methylation levels declined. This hypomethylation correlated with the appearance of V shoots in the G plantlets. A similar correlation occurred in the V phenotype, where an increase of 2 % in the global DNA methylation levels was correlated with the generation of A shoots in the V plantlets. This suggests that an "epigenetic stress memory" during in vitro conditions causes a chromatin shift that favors the generation of variegated and albino shoots.

Particular Characterisation of an In-Vitro-DTH Test to Monitor Cellular Immunity - Applications for Patient Care and Space Flight

NASA Technical Reports Server (NTRS)

Feurecker, M.; Mayer, W.; Gruber, M.; Muckenthaler, F.; Draenert, R.; Bogner, J.; Kaufmann, I.; Crucian, B.; Rykova, M.; Morukov, B.;

Classical Conditioning of Hippocampal Theta Patterns in the Rat.

DTIC Science & Technology

1976-08-01

associated with changes in performance of learned tasks , 1,4,5, 8,9 there have been very few studies of neurona l plasticity of the hippocampus It self...rapid development of a conditioned hippocampal theta response to a visual sti mulus demonstrates tha t there is considerable neurona l plasticity in the

Aversive Olfactory Learning and Associative Long-Term Memory in "Caenorhabditis elegans"

ERIC Educational Resources Information Center

Amano, Hisayuki; Maruyama, Ichiro N.

2011-01-01

The nematode "Caenorhabditis elegans" ("C. elegans") adult hermaphrodite has 302 invariant neurons and is suited for cellular and molecular studies on complex behaviors including learning and memory. Here, we have developed protocols for classical conditioning of worms with 1-propanol, as a conditioned stimulus (CS), and hydrochloride (HCl) (pH…

A Size-Distance Scaling Demonstration Based on the Holway-Boring Experiment

ERIC Educational Resources Information Center

Gallagher, Shawn P.; Hoefling, Crystal L.

2013-01-01

We explored size-distance scaling with a demonstration based on the classic Holway-Boring experiment. Undergraduate psychology majors estimated the sizes of two glowing paper circles under two conditions. In the first condition, the environment was dark and, with no depth cues available, participants ranked the circles according to their angular…

2008 Service Academy Gender Relations Survey

DTIC Science & Technology

2008-12-01

quid pro quo harassment . Three component measures of sexual harassment are derived from Q17. The...classic quid pro quo instances of specific treatment or favoritism conditioned on sexual cooperation. The measurement of these behaviors is derived from...relationship; • Sexual coercionclassic quid pro quo instances of specific treatment or favoritism conditioned on sexual cooperation. 73

Singularities in the classical Rayleigh-Taylor flow - Formation and subsequent motion

NASA Technical Reports Server (NTRS)

Tanveer, S.

1993-01-01

The creation and subsequent motion of singularities of solution to classical Rayleigh-Taylor flow (two dimensional inviscid, incompressible fluid over a vacuum) are discussed. For a specific set of initial conditions, we give analytical evidence to suggest the instantaneous formation of one or more singularities at specific points in the unphysical plane, whose locations depend sensitively on small changes in initial conditions in the physical domain. One-half power singularities are created in accordance with an earlier conjecture; however, depending on initial conditions, other forms of singularities are also possible. For a specific initial condition, we follow a numerical procedure in the unphysical plane to compute the motion of a one-half singularity. This computation confirms our previous conjecture that the approach of a one-half singularity towards the physical domain corresponds to the development of a spike at the physical interface. Under some assumptions that appear to be consistent with numerical calculations, we present analytical evidence to suggest that a singularity of the one-half type cannot impinge the physical domain in finite time.

Singularities in the classical Rayleigh-Taylor flow: Formation and subsequent motion

NASA Technical Reports Server (NTRS)

Tanveer, S.

1992-01-01

The creation and subsequent motion of singularities of solution to classical Rayleigh-Taylor flow (two dimensional inviscid, incompressible fluid over a vacuum) are discussed. For a specific set of initial conditions, we give analytical evidence to suggest the instantaneous formation of one or more singularities at specific points in the unphysical plane, whose locations depend sensitively on small changes in initial conditions in the physical domain. One-half power singularities are created in accordance with an earlier conjecture; however, depending on initial conditions, other forms of singularities are also possible. For a specific initial condition, we follow a numerical procedure in the unphysical plane to compute the motion of a one-half singularity. This computation confirms our previous conjecture that the approach of a one-half singularity towards the physical domain corresponds to the development of a spike at the physical interface. Under some assumptions that appear to be consistent with numerical calculations, we present analytical evidence to suggest that a singularity of the one-half type cannot impinge the physical domain in finite time.

Classic conditioning and dysfunctional cognitions in patients with panic disorder and agoraphobia treated with an implantable cardioverter/defibrillator.

PubMed

Godemann, F; Ahrens, B; Behrens, S; Berthold, R; Gandor, C; Lampe, F; Linden, M

2001-01-01

A model for the development of anxiety disorders (panic disorder with or without agoraphobia) is needed. Patients with an implantable cardioverter/defibrillator (ICD) are exposed to repeated electric shocks. If the theory of anxiety development by aversive classic conditioning processes is valid, these repeated shocks should lead to an increased risk of anxiety disorders. To study this hypothesis, we retrospectively studied 72 patients after implantation of an automatic ICD. Patients were assessed with the semistructured Diagnostic Interview of Psychiatric Disease 1 to 6 years after implantation of an automatic ICD. Panic disorder and/or agoraphobia was diagnosed in patients who fulfilled all DSM-III-R criteria for those conditions. Anxiety disorder developed in 15.9% of patients after ICD implantation. This was significantly related to the frequency of repeated defibrillation (shocks) to stop malignant ventricular arrhythmias. Dysfunctional cognitions are an additional vulnerability factor. The data support both the conditioning hypothesis and the cognitive model of anxiety development. These findings suggest that ICD patients are an appropriate risk population for a prospective study of the development of anxiety disorders.

In vitro assessment of skin irritation potential of surfactant-based formulations by using a 3-D skin reconstructed tissue model and cytokine response.

PubMed

Walters, Russel M; Gandolfi, Lisa; Mack, M Catherine; Fevola, Michael; Martin, Katharine; Hamilton, Mathew T; Hilberer, Allison; Barnes, Nicole; Wilt, Nathan; Nash, Jennifer R; Raabe, Hans A; Costin, Gertrude-Emilia

2016-12-01

The personal care industry is focused on developing safe, more efficacious, and increasingly milder products, that are routinely undergoing preclinical and clinical testing before becoming available for consumer use on skin. In vitro systems based on skin reconstructed equivalents are now established for the preclinical assessment of product irritation potential and as alternative testing methods to the classic Draize rabbit skin irritation test. We have used the 3-D EpiDerm™ model system to evaluate tissue viability and primary cytokine interleukin-1α release as a way to evaluate the potential dermal irritation of 224 non-ionic, amphoteric and/or anionic surfactant-containing formulations, or individual raw materials. As part of our testing programme, two representative benchmark materials with known clinical skin irritation potential were qualified through repeated testing, for use as references for the skin irritation evaluation of formulations containing new surfactant ingredients. We have established a correlation between the in vitro screening approach and clinical testing, and are continually expanding our database to enhance this correlation. This testing programme integrates the efforts of global manufacturers of personal care products that focus on the development of increasingly milder formulations to be applied to the skin, without the use of animal testing. 2016 FRAME.

Improving porcine in vitro fertilization output by simulating the oviductal environment

PubMed Central

Soriano-Úbeda, Cristina; García-Vázquez, Francisco A.; Romero-Aguirregomezcorta, Jon; Matás, Carmen

2017-01-01

Differences between the in vitro and in vivo environment in which fertilization occurs seem to play a key role in the low efficiency of porcine in vitro fertilization (IVF). This work proposes an IVF system based on the in vivo oviductal periovulatory environment. The combined use of an IVF medium at the pH found in the oviduct in the periovulatory stage (pHe 8.0), a mixture of oviductal components (cumulus-oocyte complex secretions, follicular fluid and oviductal periovulatory fluid, OFCM) and a device that interposes a physical barrier between gametes (an inverted screw cap of a Falcon tube, S) was compared with the classical system at pHe 7.4, in a 4-well multidish (W) lacking oviduct biological components. The results showed that the new IVF system reduced polyspermy and increased the final efficiency by more than 48%. This higher efficiency seems to be a direct consequence of a reduced sperm motility and lower capacitating status and it could be related to the action of OFCM components over gametes and to the increase in the sperm intracellular pH (pHi) caused by the higher pHe used. In conclusion, a medium at pH 8.0 supplemented with OFCM reduces polyspermy and improves porcine IVF output.

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

Albertini, R.J.

This work has focused on the development of in vitro T-cell mutation assays. Conditions have been defined to measure the in vitro induction of mutations at the hypoxanthine-guanine phosphoribosyl transferase (hprt) locus in human T-lymphocytes. This assay is a parallel to our in vivo hprt assay, in that the same cells are utilized. However, the in vitro assay allows for carefully controlled dose response studies. 21 refs., 16 figs., 13 tabs.

Eating disorders in women

PubMed Central

Sharan, Pratap; Sundar, A. Shyam

2015-01-01

Eating disorders, especially anorexia nervosa and bulimia nervosa have been classically described in young females in Western population. Recent research shows that they are also seen in developing countries including India. The classification of eating disorders has been expanded to include recently described conditions like binge eating disorder. Eating disorders have a multifactorial etiology. Genetic factor appear to play a major role. Recent advances in neurobiology have improved our understanding of these conditions and may possibly help us develop more effective treatments in future. Premorbid personality appears to play an important role, with differential predisposition for individual disorders. The role of cultural factors in the etiology of these conditions is debated. Culture may have a pathoplastic effect leading to non-conforming presentations like the non fat-phobic form of anorexia nervosa, which are commonly reported in developing countries. With rapid cultural transformation, the classical forms of these conditions are being described throughout the world. Diagnostic criteria have been modified to accommodate for these myriad presentations. Treatment of eating disorders can be quite challenging, given the dearth of established treatments and poor motivation/insight in these conditions. Nutritional rehabilitation and psychotherapy remains the mainstay of treatment, while pharmacotherapy may be helpful in specific situations. PMID:26330646

Three-player conflicting interest games and nonlocality

NASA Astrophysics Data System (ADS)

Bolonek-Lasoń, Katarzyna

2017-08-01

We outline the general construction of three-player games with incomplete information which fulfil the following conditions: (i) symmetry with respect to the permutations of players; (ii) the existence of an upper bound for total payoff resulting from Bell inequalities; (iii) the existence of both fair and unfair Nash equilibria saturating this bound. Conditions (i)-(iii) imply that we are dealing with conflicting interest games. An explicit example of such a game is given. A quantum counterpart of this game is considered. It is obtained by keeping the same utilities but replacing classical advisor by a quantum one. It is shown that the quantum game possesses only fair equilibria with strictly higher payoffs than in the classical case. This implies that quantum nonlocality can be used to resolve the conflict between the players.